Basic Principles of Organic Chemistry
Introduction
The main aim is to present the chemistry of organic compounds in terms
of the principles that govern their behaviour and account for their properties. The
number of known organic compounds is so large and the kinds of reactions they
engage in are so numerous and varied that it will be nearly impossible for one to
attempt to master the subject merely by acquiring a collection of facts. Organic
chemistry is a logical and consistent body of interrelated ideas. Our goal is to
perceive the relationships in terms of fundamental modes of behaviour.
Organic chemistry deals with the chemical compounds of carbon and
principally with compounds in which carbon is combined with hydrogen, oxygen,
nitrogen, sulphur and the halogens.
The naturally occurring organic compounds are of concern to the
biochemist as well as the organic chemist. For this biochemistry and organic
chemistry come together and lose their individual identity. The naturally
occurring compounds include the proteins, fats, carbohydrates, vitamins, and
hormones that make up the structure of living cells. They also include many of
the drugs that man uses to control disease, the perfumes and colours of the plant
world.
The synthetic organic compounds are derived largely from natural sources
of carbon-coal and petroleum-but are the products of man’s voluntary ingenuity
rather than of the involuntary activities of growing organisms.
Towards the end of eighteenth century chemicals began to turn to the
examination of living organisms, and many compounds were isolated from plant
and animal sources. The ancient Egyptians used organic compounds such as
indigo and alizarin to dye cloth. The famous ‘royal blue’ used by the Phoenicians
was also an organic substance, obtained from molecules. Some organic
substances such as strychnine (C21H22N2O2), quinine (C20H24N2O2) and morphine
(C17H19O3N) were isolated in a crystalline form from plants of medicinal
importance. Their structure remained unknown for 100 years. The fermentation
of grapes of produce ethyl alcohol and the acidic qualities of ‘soured wine’ are
both described in the Bible and were probably known earlier.
Carbon compounds have different properties than do the minerals taken
from the ground or the sea. They dissolve in different solvents and are generally
more delicate than their mineral counterparts. They are often gases, liquids, or
low melting solids. The forces that hold organic molecules together are weaker
than the ionic forces of inorganic salts.
Organic compounds are vitally important to the prosperity of a nation.
Shortage of petroleum-based fuels might cause nations to fight. The drugs that
cure disease, control epidemic are organic compounds. The foods we eat, whether
natural or artificial, are compounds of carbon. Pesticides that control plant
disease, weed growth and plant destruction by insects and rodents are organic
compounds.
Synthetic fibres and plastics that have revolutionized our industrial
economy are mostly carbon-containing materials. With organic chemicals we
clean ourselves and our clothes, run our automobiles, and heat our homes but we
also pollute our environment.
There are two large reservoirs of organic material from which simple
organic compounds can be obtained (petroleum and coal). Simple organic
compounds are in turn used as building blocks from which larger and more
complicated compounds can be made.
Organic molecules containing thousands of atoms are known, and the
arrangement of atoms in even relatively small molecules a=can be very
complicated. One of the major problem in organic chemistry is to find out how
the atoms are arranged in molecules, that is, to determine the structure of the
compound.
The science of organic chemistry is less than 200 years old. Prior to 1850,
chemists believed that there was something distinctive about organic compounds
that would prevent their preparation outside of living organisms. It was believed
that the intervention of a vital force was necessary for their creation. In 1828
Friedrich Wohler found that the organic compound Urea H2NCONH2 (a
constituent of urine could be made by heating the inorganic compound
ammonium cyanate NH4CNO.
Although ‘vitalism’ died slowly and did not disappear completely from
scientific circles until 1850, its passing made possible the flowering of the science
of organic chemistry that has occurred since 1850.
Chapter 1
Hydrocarbons
Hydrocarbons are compounds that contain only carbon and hydrogen it
may be: Saturated which are the simplest class of organic compounds contain
only single bond (sigma α) like alkanes and cycloalkanes or Unsaturated contain
only one or more double or triple bonds (pi: π) like alkenes, alkynes, unsaturated
alicyclic and aromatic hydrocarbons.
Alkanes and Cycloalkanes
Alkanes: are hydrocarbons in which all C-C bonds are single bond (sigma:
α). General formula CnH2n+2.
Cycloalkanes: are alkanes in which all or some of the carbon atoms are
arranged in a ring (i.e. cyclic structure). General formula CnH2n (i.e. two fewer
hydrogen atoms than alkanes).
Suppose the molecular formula of saturated hydrocarbon C nH2n-2 then the
compound contains two rings…. etc., but in all cases they do not contain a double
bond but a ring structure.
Structure and shape of alkanes
Methane CH4 and ethane C2H6, are the first members of alkane.
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Each carbon atom is tetrahedral, and all bond angles are approximately
109.5o, and the next members of the series are:
Propane
CH3CH2CH3
Butane
CH3CH2CH2CH3 or CH3(CH2)2CH3
Pentane
CH3CH2CH2CH2CH3 or CH3(CH2)3CH3
The structural formula of each member differs by one ¬CH2¬ (methylene)
group from the next member. The methylene groups are grouped together in a
condensed structural formula as represented above. The following table
represents: names, molecular formula, and condensed structural formulas for
some alkanes:
Table 1:
Name
Mol.
Condensed
Name
Mol.
Condensed
Formula
formula
Hexane
C6H14
CH3(CH2)4CH3
Hexadecane
C16H34
CH3(CH2)14CH3
Heptane
C7H16
CH3(CH2)5CH3
Heptadecane C17H36
CH3(CH2)15CH3
Octane
C8H18
CH3(CH2)6CH3
Octadecane
C18H38
CH3(CH2)16CH3
Nonane
C9H20
CH3(CH2)7CH3
Nonadecane
C19H40
CH3(CH2)17CH3
Decane
C10H22
CH3(CH2)8CH3
Eicosane
C20H42
CH3(CH2)18CH3
Undecane
C11H24
CH3(CH2)9CH3
Hencosane
C21H44
CH3(CH2)19CH3
Dodecane
C12H26
CH3(CH2)10CH3 Docosane
C22H46
CH3(CH2)20CH3
Tridecane
C13H28
CH3(CH2)11CH3 Tricosane
C23H48
CH3(CH2)21CH3
Tetradecane
C14H30
CH3(CH2)12CH3 Tetracosane
C24H50
CH3(CH2)22CH3
Pentadecane
C15H32
CH3(CH2)13CH3 Pentacosane
C25H52
CH3(CH2)23CH3
Formula formula
Nomenclature of alkanes
A) IUPAC (systematic) names:
The International Union of Pure and Applied Chemistry (IUPAC) was
established a set of rules for naming alkanes. Alkanes with an unbranched
chain of carbon atoms consist of two parts: a prefix that indicates the
number of carbon atoms in the chain (as underlined in table 1), and the
suffix –ane to show that the compound is a saturated hydrocarbon. For
substituted alkanes
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IUPAC gives a parent or root name that indicates the longest chain of carbon
atoms in the compound and substituent name(s) that indicate the group attached
to the parent chain e.g.,
A substituent group derived from alkane by removal of an H atom is called
an alkyl group. The symbol R- is commonly used to represent an alkyl group.
Alkyl groups are named by dropping the –ane from the name of the parent alkane
and adding the suffix –yl e.g., ethane gives ethyl…. etc.
Following are the rules of the IUPAC system for naming alkanes:
1) The general name of a saturated hydrocarbon is alkane.
2) For branched-chain alkanes, the hydrocarbon derived from the longest
chain of carbon atoms is taken as the parent chain and the root or stem
name is that of the parent alkane.
3) Group(s) attached to the parent chain is called substituent(s). Each
substituent is given a name and number. The number shows the carbon
atom of the parent chain to which the substituent is attached.
4) If the same substituent occurs more than once, the number of each carbon
of the parent chain on which the substituent occurs is given. In addition,
the number of time the substituent group occurs is indicated by a prefix ditri-, tetra-, penta-, hexa-, hepta-, octa-, nona-, deca-, and so on.
5) If there is one substituent, number the parent chain from the end that gives
in the lower number.
6) If there are two or more identical substituents, number the parent chain
from the end that gives the lower number to the substituent encountered
first.
7) If there are two or more different substituents, list them in alphabetical
order and number the chain from the end that gives the lower number to
the substituent encountered first.
If there are different substituents in equivalent position on the parent chain,
the substituent of lower alphabetical order is given the lower number.
8) When branching first occurs at an equal distance from either end of the
longest chain, choose the name that gives the lower number at the first
point of difference.
Hyphenated prefixes, such as sec- and tert-, are not considered when
alphabetizing. The prefix iso- is not a hyphenated prefix and, therefore, is
included when alphabetizing e.g.:
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N.B.:
The numbering of the branched alkyl groups always begins at the point of
their attachments to the main chain.
Example 1:
Give IUPAC names for the following alkane:
(parent chain of four carbon atoms i.e., butane)
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(parent chain of six carbon atoms i.e., hexane)
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The longest chain contains six carbons, and, therefore, the parent chain is
a hexane (rule 2). There are two alkyl substituents: a methyl group and an ethyl
group. The hexane chain must be numbered so that the substituent encountered
first (the methyl group) is on carbon 2 of the chain (rule 6). The ethyl and methyl
substituents are listed in alphabetical order (rule 7) to give the name 4-ethyl-2methylhexane.
(parent chain of six carbon atoms i.e., hexane)
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The longest chain contains six carbon atoms, and, therefore, the parent
chain is a hexane (rule 2). The two different substituents are un-equivalent
locations on the parent chain: numbering from the left gives methyl on carbon 3;
numbering from the right gives ethyl on carbon 3. When listed in alphabetical
order, ethyl comes before methyl. Therefore, number the carbon chain in this
molecule to give the ethyl the lower number (rule 7).
B) Common names
In the order system of common nomenclature, the total number of carbon
atoms in an alkane, regardless of their arrangement, determines the name. The
first three alkanes are methane, ethane, and propane. Alkanes of formula C 4H10
called butanes, all alkanes of formula C5H12 are called pentanes, and those of
formula C6H14 are called hexanes. For alkanes beyond propane, normal, or n-, is
used to indicate that all carbons are joined in a continuous chain, and iso is used
to indicate that one end of continuous chain terminates in a (CH3)2CH- group.
The first compounds of molecular formula C5H12 to be discovered and named
were pentane and its isomer, isopentane. Subsequently, another compound of
molecular C5H12 was discovered and because it was a ‘new’ pentane (at least it
was new to those who first discovered it), this isomer was named neopentane
(greek: neo = new). The prefix neo is used to indicate that one end of an otherwise
continuous chain terminates in (CH3)3C-. Following are examples of common
names:
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Similarly, hydrogen is also classified as primary (1 o), secondary (2o), or
tertiary (3o) depending on the type of carbon to which each is bonded. Those
attached to primary carbons are classified as primary hydrogen, those on
secondary carbons are secondary hydrogen, and those on tertiary carbons are
tertiary hydrogen. Hydrogen atoms in a compound can be divided into equivalent
sets. Equivalent hydrogen has the same chemical environment. A direct way to
determine which hydrogen in a molecule is equivalent is to replace each in turn
by a ‘test atom’, as for example a halogen atom. If replacement of two different
hydrogens by a ‘halogen test’ gives the same compound, the hydrogens are
equivalent. If replacement gives different compound, the hydrogen is nonequivalent. Using this test, we can show that propane contains two sets of
equivalent hydrogen a set of six equivalent primary hydrogens, and a set of two
equivalent secondary hydrogens. Replacement of any of these six hydrogens by
chlorine gives 1-chloropropane whereas replacement one of the two equivalent
hydrogen gives 2-chloropropane.
Cycloalkanes
A molecule that contains carbon atoms joined together to form a ring is
called a cyclic hydrocarbon. Furthermore, when all carbons of the ring are
saturated, the molecule is called a cycloalkane.
Structure and nomenclature
A) Cycloalkanes
Cycloalkanes of ring sized ranging from 3 to over 30 are found in nature, and
in principle, there is no limit to ring size. The use of carbon bonds to close a ring
means that cycloalkanes contain two fewer hydrogen atoms than alkanes of same
number of carbon atoms. For example, compare the molecular formulas of
cyclopropane (C3H6) and propane (C3H8) or those of cyclohexane (C6H12) and
hexane (C6H14).
Five-member rings (cyclopentanes) and six-member rings (cyclohexanes)
are especially abundant in nature and, therefore, have received special attention.
The rings are represented by regular polygons having the same number of sides.
For example, cyclopropane is represented by a triangle and cyclohexane by a
hexagon. The angle C-C-C in a regular polyhedral structure is determined by the
equation:
Angle = (n-2) / n x 180
(n: is the number of sides).
The name cycloalkanes, prefix the name of the corresponding open-chain
hydrocarbon with cyclo-, and name each substituent on the ring. If there is only
a single substituent in the ring it does not take any number. If there are two or
more substituents, each substituent must be given a number of indicate its location
on the ring beginning with the substituent first in alphabet and then follow the
direction that gives the next substituent the lowest possible number.
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B) Bicyclic compounds
1- Bridged ring system
Any organic compound that contains one ring is classified as monocyclic.
Examples of monocyclic alkanes are cyclopentane, cyclohexane, and their simple
derivatives. Compounds that contain two rings but which share no atoms in
common are similarly classified as monocyclic. A hydrocarbon that contains two
rings that share two carbon atoms is classified as a bicycloalkane. Atoms shared
by the two rings in a bicyclic compound are called bridgehead atoms.
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Bicyclopentane known as: Bicyclo[2.2.1] heptane (or Norbornane) IUPAC
names of bicycloalkanes are derived in the following way:
1) Numbering begins at a one bridgehead carbon atom and proceeds along the
longest bridge to the second bridgehead carbon, then along the next longest
bridge back to the original bridgehead carbon, and so on until all atoms are
numbered.
2) The parent name of a bicycloalkane is that of the hydrocarbon of the same
number of carbon atoms as are in the bicyclic ring system.
3) Ring sizes are shown by counting the number of carbon atoms linked to
the bridgeheads and placing them in decreasing order in brackets between
the prefix bicycle- and the parent name.
4) The name and location of substituents are shown by the rules already
described in IUPAC.
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2- Spiroalkanes
A cycloalkane in which two rings share only one carbon atoms is known as
spiroalkane (Latin: spiro, spiral or coiled), and the single carbon atom shared by
the two rings is called a spiro carbon. Numbering a spiroalkane begins at the
carbon on the shorter bridge nearest the spiro carbon, along the shorter bridge,
through the spirocarbon, and along the longer bridge, the four bonds connected
to a spiro carbon create two planes at right angles to each other, and consequently,
the two rings thus intersecting lie at right angles to each other.
Examples:
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Synthesis of alkanes
1- By the hydrogenation of alkenes or alkynes:
This is readily achieved catalytically by shaking an alkene (or alkyne) under
hydrogen at room temperature and at atmospheric pressure in presence of a
transition metal catalyst as platinum or palladium. Higher temperature and
pressure are used with finely divided nickel catalyst. The reaction is carried out
in ethanol or in another organic solvent and the process is called catalytic
reduction or alternatively catalytic hydrogenation, as two hydrogens’ are added
to the carbon-carbon double bond mostly by syn-addition (addition of hydrogen
from the same side), without free rotation at the intermediate stage.
𝑡𝑟𝑎𝑛𝑠𝑖𝑡𝑖𝑜𝑛 𝑚𝑒𝑡𝑎𝑙 𝑐𝑎𝑡𝑎𝑙𝑦𝑠𝑡
𝐶𝐻2 = 𝐶𝐻2 + 𝐻2 →
𝐶𝐻3 𝐶𝐻3
Ethylene
Ethane
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2- By the reduction of aldehydes and ketones:
One method for converting carbonyl group to methylene group is the
Clemmensen reduction. It involves the use of zinc amalgam in the presence of
concentrated hydrochloric acid.
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When Clemmensen reduction fails or when strongly acidic conditions are not
required owing to the presence of acid-sensitive functional groups, the WolffKishner reduction may succeed. In this reduction, the aldehyde or ketone is
treated with hydrazine to form a hydrazone which is then heated with sodium
hydroxide or other basic compound in a high boiling solvent.
3- By the hydrolysis of the alkyl-magnesium halides:
A very satisfactory procedure to effect this conversion is the hydrolysis of the
corresponding alkyl-magnesium halide (Grignard’s reagents).
𝑅 − 𝑋 + 𝑀𝑔 → 𝑅− : (𝑀𝑔𝑋)+ + 𝐻2 𝑂 → 𝑅𝐻 ↑ +𝑀𝑔𝑋𝑂𝐻
The alkyl-magnesium halide is formed by reaction between magnesium turning
and alkyl halide in dry ether. The conversion is quantitative and this is made use
of in the Zerewitinoff method for the determination of active hydrogen (e.g. ≡ 𝐶-
H, ¬OH, ¬SH, ¬NH2, ¬COOH, etc.). The compound is allowed to react with an
excess of methylmagnesium iodide and the methane evolved is measured in a gas
burette.
4- By coupling reaction using organometallic compounds:
This type of symmetrical coupling (the connection of two groups, C-C σ-bond)
is called the Wurtz reaction. The unsymmetrical coupling reactions are called
cross-coupling reactions or mixed Wurtz reaction and gives mixture of products:
𝑅1 − 𝑋 + 𝑅2 − 𝑋 + 2𝑁𝑎 → 𝑅1 − 𝑅 2 + 𝑅1 − 𝑅2 − 𝑅2 + 2𝑁𝑎𝑋
When a mixture of an alkyl and aryl halides is treated with sodium it gives
alkylated aromatic compound (The Wurtz-Fitting reaction).
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One type of Wurtz reaction is the closing of small rings especially three
membered rings in mono-, bi- or polycyclic compounds.
Coupling can also be achieved by the use of copper ‘ate’ complexes. The
organo-copper reagent, lithium dialkyl cuprate, is formed by reacting cuprous
halide with alkyl lithium compound. Lithium dialkyl cuprate reacts with alkyl
halides through an SN2 mechanism to give higher alkanes. This coupling reaction
is known as Corey-House synthesis.
𝑅1 𝐿𝑖 + 𝐶𝑢𝑋 → (𝑅1 )2 𝐶𝑢𝐿𝑖 + 𝐿𝑖𝑋
Lithium dialkyl cuprate
(𝑅1 )2 𝐶𝑢𝐿𝑖 + 𝑅2 𝑋 → 𝑅1 − 𝑅2 + 𝑅1 𝐶𝑢 + 𝐿𝑖𝑋
The nucleophile is a carbonium part of an organometallic compound. The
attacking carbon brings a pair of electrons with it to the new carbon-carbon bond
but there is much that is still not known about the mechanism of these reactions
and many of them are not nucleophilic at all. Dihalides in which halogens in a
1,3-or (α-, γ-) relationship are converted to cyclopropane derivatives by treatment
with zinc in ethanol. This reaction is a γ-elimination:
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5- By electrolysis (from carboxylic acids by decarboxylation):
Electro-organic chemistry is the study of the oxidation and reduction of organic
molecules and ions. The initial step involves an anodic oxidation of the
carboxylate anion to a radical, which then dimerises to the alkane.
𝑅𝐶𝑂𝑂− → 𝑅∗ + 𝐶𝑂2
𝑅∗ + 𝑅∗ → 𝑅 − 𝑅
The synthesis of alkanes, which involves the electrolysis of salts of
carboxylic acids, was first reported by Kolbe.
2 𝐶𝐻3 (𝐶𝐻2 )12 𝐶𝑂𝑂− → 𝐶26 𝐻54 + 2𝐶𝑂2
Hexacosane
6- Addition of carbenes to alkenes:
The simplest carbine (methylene, as a parent electrophile), adds to alkene to give
cyclopropanes through a stereospecific syn-addition.
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Methylene can be obtained through the decomposition of diazomethane by
heating or pyrolysis:
Dichlorocarbenes are more frequently electrolysed in the synthesis of
cyclopropane derivatives from alkenes:
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7- Cyclopropanes through Simmons-Smith reaction:
The reagent resembles iodomethylzinc iodide and is called carbenoid as they
contain a divalent carbon atom but does not liberate carbene:
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Physical properties of alkanes and cycloalkanes
The low molecular weight alkanes, such as methane, ethane, propane, and
butane are gases at room temperature and atmospheric pressure. Alkanes of
higher molecular weight, such as those in gasoline and kerosene are liquids. Very
high molecular weight alkanes, such as those found in paraffin wax, are solids.
Methane can be converted to a liquid if cooled to -164oc and to a solid if
further cooled to -182oc. The fact that methane (or any other compound, for that
matter) can exist as a liquid or solid depends on the existence of intermolecular
forces of attraction between particles of each pure compound. Although the forces
of attraction between particles are all electrostatic in nature, they vary widely in
their relative strengths. The strongest attractive forces are those between ions, for
example between Na+ and Cl- in NaCl (188 kcal/mol.). Weaker are dipole-dipole
interactions and hydrogen bonding (20.10 kcal/mol.). In non-polar compounds as
alkanes the attractive intermolecular forces are known as dispersion forces or van
der Waals forces.
The strength of dispersion forces depends on how easily an electron cloud
can be polarized. Electrons in small atoms and molecules tend to be held closer
to their nuclei and therefore, are not easily polarized. For this reason, the strength
of dispersion forces tends to increase with increasing molecular mass and size.
Intermolecular interactions between Cl2 molecules and between Br2 molecules
are estimated to be 0.7 kcal/mol. and 1.0 kcal/mol. respectively.
Dispersion forces are inversely proportional to d where d is the distance
between particles, and are important only when interacting particles are very
close together. For dispersion forces to be important, the interacting particles
must be in virtual contact with one another. Now let us use these concepts of the
nature of intermolecular forces to examine the relationships between the physical
properties of alkanes and their molecular structure. Alkanes are non-polar
compounds, and the only forces of attraction between them are dispersion forces.
Because interactions between molecules are so weak, boiling points of alkane are
lower than those of almost any other type of compound of the same molecular
weight of the number of atoms and molecular weight of an alkane increase, the
strength of dispersion forces per molecule also increases. Therefore, the boiling
points of alkanes increase as molecular weight increases.
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Melting points of alkanes also increase with increasing molecular weight.
The increase, however, is not as regular as that observed for boiling points
because the packing of molecules into ordered patterns changes as molecular size
and shape (branching).
Alkanes that are constitutional isomers with each other are different
compounds and have different physical and chemical properties. The boiling
points of each of the branched-chain isomers of C6H14 is lower than that of nhexane itself, and the more branching there is, the lower the boiling point. These
differences in boiling points are related to molecular shape in the following way.
As branching increases, the shape of an alkane molecule becomes more compact
and its surface area decreases. As surface area decreases, contact between
adjacent molecules decreases, the strength of dispersion forces decreases, and
boiling point also decreases. For any group of alkane constitutional isomers, it is
usually observed that the least branched isomer has the lowest boiling point. The
cycloalkanes are held in a more compact cyclic shape, so their boiling points are
higher than those of unbranched alkanes with the same number of carbon atoms.
All liquid alkanes are less dense than water (1.0 g/ml).
Reactions of alkanes and cycloalkanes
Alkanes (known as paraffins i.e. low affinity) and cycloalkanes are quite
non-reactive toward most reagents, a behaviour consistent with the fact that they
are non-polar compounds and contain only strong sigma (σ-) bonds (absence of
unshared pairs of electrons, an electron deficient atom or an atom with an
expandable octet). However, some saturated hydrocarbons do react under certain
conditions with oxygen and with halogen and the strained cyclic hydrocarbons
(cyclopropane and cyclobutane) can react by addition.
1- Oxidation (or combustion)
By far the most economically important reaction of alkanes is their oxidation
(combustion) by O2 to form carbon dioxide and water. Oxidation of saturated
hydrocarbons is the basis for their use as energy sources for heat (natural gas,
liquefied petroleum gas [LPG], and fuel oil) and power (gasoline, diesel fuel, and
aviation fuel). Following are balanced equations for complete oxidation of
methane, the major component of natural gas, and 2,24-trimethylpentane, a
component of gasoline.
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2- Halogenation
Is the substitution of a hydrogen atom of an alkane by a halogen, mostly chlorine
or bromine as the fluorine resulted in an exothermic reaction difficult to control
and iodine resulted in an endothermic reaction which favours the formation of
reactants? The reaction is a substitution reaction
𝑙𝑖𝑔ℎ𝑡 𝑜𝑟 ∆
𝐶𝐻4 + 𝐶𝑙2 →
𝐶𝐻3 𝐶𝑙 + 𝐻𝐶𝑙
Chloromethane (methyl chloride)
Chlorination or bromination of alkane proceeds by a radical chain
mechanism initiated by dissociation of halogen into halogen atoms (radicals). The
energy needed (bond dissociation energy can be brought about by visible or
ultraviolet light or by heating to temperature above 400oc.
If chloromethane is allowed to react with chlorine, further chlorination
produces a mixture of dichloromethane (methyl chloride), trichloromethane
(chloroform), and tetrachloromethane (carbon tetrachloride) is formed.
𝐶𝐻3 𝐶𝑙 + 𝐶𝑙2 ⟶ 𝐶𝐻2 𝐶𝑙2 + 𝐻𝐶𝑙
𝐶𝐻2 𝐶𝑙2 + 𝐶𝑙2 ⟶ 𝐶𝐻𝐶𝑙3 + 𝐻𝐶𝑙
𝐶𝐻𝐶𝑙3 + 𝐶𝑙2 ⟶ 𝐶𝐶𝑙4 + 𝐻𝐶𝑙
Treatment of propane with bromine gives a pair of constitutional isomers,
namely 1-bromopropane (propyl bromide) and 2-bromopropane (isopropyl
bromide).
𝐶𝐻3 − 𝐶𝐻2 − 𝐶𝐻3 + 𝐵𝑟2 ⟶ 𝐶𝐻3 − 𝐶𝐻2 − 𝐶𝐻2 − 𝐵𝑟 + 𝐶𝐻3 − 𝐶𝐻𝐵𝑟 − 𝐶𝐻3
Propane
1-bromopropane (8%)
2-bromopropane (92%
The substitution of bromine is favoured on a secondary hydrogen over a
primary hydrogen and so 2-bromopropane is the major product. Therefore, the
bromination of alkane is selective in the order:
Tertiary > Secondary > Primary hydrogen
Generally, the reaction in which one direction of bond making or bond
breaking occurs preferentially to all other directions is known as regioselective
reaction.
Reactivity-selectivity principle
If the attacking species is more reactive it will be less selective, and the
yield will be close to those expected from the probability factor. The cycloalkanes
like methane and ethane contain equivalent hydrogens and therefore their
halogenation gives only one mono-substituted product, e.g.
33‫تركيب ص‬
Many halogenated hydrocarbons have found wide commercial use as
solvents, refrigerants, dry-cleaning agents, local and inhalation anaesthetics, and
insecticides.
The fluoralkanes can be formed by treating chloroalkanes with HF in the
presence of antimony (V) fluoride, SbF5, as catalyst. The resulting
chlorofluorocarbons (CFCS) is used as heat transfer media in refrigeration system
and as propellant for aerosol sprays, e.g. the trichlorofluorocarbon (CCl 3F0 is
known as Freon-11.
𝑆𝑏𝐹5
𝐶𝐶𝑙4 + 𝐻𝐹 →
𝐶𝐶𝑙3 𝐹 + 𝐻𝐶𝑙
Trichlorofluorocarbon (Freon-II)
CFCs escape to the stratosphere (ozone layer) and cause destruction of the
ozone layer as they absorb ultraviolet radiation form the sun and then
decomposes. The chemical industry developing non-ozone depleting alternatives
to CFCs, e.g. hydrofluorocarbons (HFCs) and hydrofluorochlorocarbons
(HCFCs). Artificial blood is a trans-perfluorodecaline is used as oxygen carrying
blood substitute.
Sources of alkanes
a) Natural gas: consists of about 90% methane, 10% ethane and a mixture of
relatively low boiling alkanes.
b) Petroleum and coal.
Unsaturated Hydrocarbons
I-
Alkenes
Alkenes are hydrocarbons with carbon-carbon double bonds. Alkenes are
sometimes called olefins, from olefiant gas (oil-forming gas) an old name for
ethylene. The simplest alkene is ethylene, with general formula CnH2n (C2H4).
Nomenclature of alkenes:
a) IUPAC system
The following points summarize the IUPAC rules for naming alkenes:
1) Select the longest chain that contain the largest possible number of double
bonds and name after their alkane parents but with the –ane ending changed
to –ene. If there are two double bonds, the suffix is diene; for three, triene;
for four, tetraene; and so on.
36 ‫تركيب ص‬
2) Number the chain from the end closest to the double bonds. Number a ring
so that the double bond is between carbon 1 and 2.
3) Place the numbers giving the locations of the double bonds in front of the
root name.
4) Name substituent groups as in alkanes, indicating their locations by the
number of the main-chain carbon to which they are attached.
37‫تركيب ص‬
Alkenes as substituents: when there is functionality of higher nomenclature
priority, the chain is numbered from the end that gives the lowest number to this
functional group. The prefix number specifies the carbon atom in the chain where
the double bond begins.
38‫تركيب ص‬
Naming stereoisomeric alkenes
Cis-trans nomenclature: if two similar groups bonded to the carbons of the
double bond are on the same side of the bond, the alkene is the cis isomer. If the
similar groups are on opposite sides of the bond, the alkene is trans. Not all
alkenes are capable of showing geometric isomerism. If either carbon of the
double bond holds two identical groups, the molecule cannot have cis and trans
forms.
38‫تركيب ص‬
Trans-cycloalkenes are unstable unless the ring is large enough (at least
eight carbon atoms) to accommodate the trans double bond. Therefore, all
cycloalkenes are assumed to be cis unless they are specifically named trans. The
cis rarely used with cycloalkenes, except to distinguish a large cycloalkane from
its trans isomer.
39‫تركيب ص‬
E-Z Nomenclature: The cis-trans nomenclature for geometric isomers fails to
give an ambiguous name. For example, the isomers of 1-bromo-1-chloropropene
are not clearly cis or trans because it is not obvious which substituents are referred
to as being cis or trans.
39‫تركيب ص‬
In response to this problem we use the E-Z system. In this system the two
groups attached to each end of the double bond are assigned priority numbers
according to the Cahn-Ingold-Prelog conversion for chiral carbon atoms which is
based on atomic number criterion. When the two groups of highest priority
number are on the same side of the molecule, the compound is the Z isomer
(German, Zusammen = together). When the two groups of highest priority are on
opposite side of the molecule, the compound is the E form (Ger., Entgegen =
opposite).
40‫تركيب ص‬
Cahn-Ingold-Prelog priority rules:
1) If the atoms in question are different, the sequence order is by atomic
number, with the atom of highest atomic number receiving the highest
priority.
F < Cl < Br < I
2) If two isotopes of the same element are present, the isotope of higher mass
receives the higher priority.
3) If two atoms are identical, the atomic number of the next atoms is used for
priority assignment. If these atoms also have identical atoms attached to
them, priority is determined at the first point of difference along the chain.
The atom that has attached to it an atom of higher priority has the higher
priority. (Do not use the sums of the atomic numbers, but look for the single
atom of highest priority).
42‫تركيب ص‬
Groups containing double or triple bonds are assigned priorities as if both
atoms were duplicated or triplicated.
4) When it is necessary to consider substituents on a multiply bonded atom,
the atom from which the multiple bond originates is counted.
43 ،42‫تركيب ص‬
Example:
43‫تركيب ص‬
b) Common names:
Most alkenes are conveniently named by the IUPAC system, but common names
are sometimes used for the simplest compounds
43‫تركيب ص‬
The ethyl group CH2=CH- and the propenyl group CH2=CHCH2- are
usually called the vinyl group and allyl group, respectively.
Nomenclature priorities of selected functional groups:
All the functional groups below a given in the table are named as
substituents’ on a parent compound that contain anyone of the functional groups
above it.
Certain functional groups are not given any priority and are always named
as substituents, i.e. it has only prefix names. These are halogens (F, Cl, Br, I), the
nitro and the ethers, alkoxy or aryloxy.
Functional group
*
free
radicals,
Parent (suffix)
Substituent (prefix)
anion, Onium ion
cation as N(CH3)3+
*
COOH
-oic acid or carboxylic Carboxy
acid
*
SO3H
Sulfonic acid
Sulfo
COOR
Alkyl-oate
Alkoxycarbonyl
COOAr
Aryl-oate
Aryloxycarbonyl
COX
Oyl halide
Haloformyl
CONH2
Amide
Carbamoyl
CN
Nitrile
Cyanoi
CHO
-al (carbaldehyde)
Oxo- (formyl)
C=O
-one
Oxo
R-OH or Ar-OH
-ol
Hydroxyl
SH
Thiol
Mercapto
NH2
Amine
Amino
-C=C-
-ene
Alkenyl
-𝐶 ≡ 𝐶-
-yne
alkynyl
Examples:
46‫تركيب ص‬
Structure and bonding in alkenes
Ethylene is a planar molecule, and the carbon-carbon double bond with its
four attached atomsis a planar structural unit in higher alkenes. Bonding in
alkenes is described according to an sp2 orbital hybridization model. The double
bond unites two sp2 hybridized carbon atoms and is made up of a σ component
and a π component. The σ bond arises by overlap of a sp2 hybrid orbital on each
carbon. The π bond is weaker than the σ bond and results from a side-by-side
overlap of p-orbital.
46‫تركيب ص‬
Physical properties of alkene:
The physical properties of alkenes are practically identical to those of the
corresponding alkenes. The boiling points of alkenes increase smoothly with
molecular weight (about 30o per CH2 group). As with alkanes, increased
branching leads to greater volatility and lower boiling points. Like alkanes,
alkenes are relatively non-polar. They are insoluble in water but soluble in nonpolar solvents such as hexane and ethers. Alkenes tend to be slightly more polar
than alkanes, however, because the more weakly held electrons in the π-bond are
more polarized and because the vinylic bonds tend to be slightly polar.
47‫تركيب ص‬
Alkyl groups are slightly electron-donating toward a double bond, helping
to stabilize it. The general order of alkene stability is:
R2C=CR2 > R2C=CHR > Trans RCH=CHR > Cis RCH=CHR > RCH=CH2 >
CH2=CH2
N.B:
The cis isomer is destabilized by the van der Waals repulsion between the
bulky groups on the same side of the double bond. Exceptions are cycloalkenes,
cis-cycloalkenes being more stable than trans when the ring contains fewer than
11 carbons. The strain eventually disappears when a 12-membered ring is
reached. When the rings are larger than 12-membered, trans-cycloalkenes are
more stable than cis because the ring is large enough and flexible enough that is
energetically similar to a noncyclic alkene.
48‫تركيب ص‬
Cyclopropene is even more strained because the deviation of the bond
angles at its doubly bonded carbons from the normal sp 2 hybridization value of
120o is greater still. Cyclopropenyllium cation is the smallest compound with
aromatic character, it possesses 2π electrons, according to Huckel rule (to be
aromatic, a monocyclic planar compound must have (4n+2) π electron, where n
is an integer 0, 1, 2, ….]. Cyclobutene has, of course, less angel strain than
cyclopropene, and the angle stain of cyclopentene, cyclohexene, and higher
cycloalkenes are negligible.
49‫تركيب ص‬
The stability of bicyclic bridged compounds obeys Bredt’s rule, which
stated that “A bridged cicyclic compounds cannot have a double bond at a
bridgehead position unless one of the rings contains at least eight carbon atoms.
50‫تركيب ص‬
General methods of preparation
1- Dehydration of alcohols:
In the dehydration of alcohols, the elements of water are eliminated from adjacent
carbons. An acid catalysis is necessary. Sulphuric acid (H2SO4) and phosphoric
acid (H3PO4) are the acid most frequently used in alcohol dehydration reactions.
Potassium hydrogen sulphate (KHSO4) is also often used.
51‫تركيب ص‬
The dehydration of alcohols is regioselective, i.e. β-elimination can occur
in either of two directions to yield constitutionally isomeric alkenes, but one
alkene is formed in greater amounts than the other. The acid-catalysed
dehydration of alcohols obeys Zaitsev’s rule. In the original form it is stated that
“the alkene formed in greatest amount is the one that corresponds to removal of
the hydrogen from the β-carbon having the fewest hydrogen substituents”. It is
now more expressed in different ways. β-elimination reactions of alcohols yield
the most highly substituted alkene as the major product, or the predominant
formation of the most stable alkene that could arise by β-elimination.
52‫تركيب ص‬
In addition to being regioselective, alcohol dehydration reactions are
stereoselective, i.e. it is one in which a single starting material can yield two or
more stereoisomeric products, but gives one of them, which is the most stable, in
greater amount than any other.
52‫تركيب ص‬
Reaction mechanism:
The relative ease with which alcohols undergo dehydration is in the
following order:
R3CH-OH > R2CHOH > RCH2OH
3o
2o
1o
53‫تركيب ص‬
Some primary and secondary alcohols also undergo rearrangements of
their carbon skeleton through 1,2-shift of hydride or alkyl group to more stable
carbocation during dehydration.
54‫تركيب ص‬
The presence of a carbonyl group in a compound containing an alcoholic
function may influence the ease of elimination of the hydroxyl group. An αhydrogen is activated by the carbonyl group and water is eliminated very easily
under acid or base catalysis, such conjugated system has a special stability.
54‫تركيب ص‬
2- Dehydrohalogenation of alkyl halides:
It is the removal of hydrogen halide (HX) from an alkyl halide by β-elimination.
The reaction is carried out in the presence of strong base in a suitable solvent such
as sodium ethoxide in ethyl alcohol, sodium methoxide in methyl alcohol and
potassium hydroxide in ethyl alcohol. Potassium tertbutoxide is the preferred base
when the alkyl halide is primary; it is used in either tert-butyl alcohol or
dimethylsulfoxide as solvent.
55‫تركيب ص‬
The regioselectivity of dehydrohalogenation of alkyl halides follows
Zatisev rule; β-elimination predominates in the direction that leads to the more
stable one, which is formed by removing a proton from the β-carbon that has the
fewest hydrogen substituents.
56‫تركيب ص‬
In addition to being regioselective, dehydrohalogenation of alkyl halides is
stereoselective and favours formation of the more stable stereoisomer. Usually,
the trans is formed in greater amounts than its cis stereoisomer. The order of alkyl
halide reactivity is:
Tertiary > Secondary > Primary
Reaction mechanism:
The dehydrohalogenation is almost always better achieved by E2 reaction.
57‫تركيب ص‬
The base abstracts proton from the β-carbon while the bond between the
halogen and the α-carbon undergoes heterolytic cleavage. The hydrogen
abstracted and the halide lost must be in an anti-planer relationship to one another
at the transition state in order to allow the developing p-orbitals to overlap with
one another to form a π-bond. In the absence of strong base, alkyl halides
eliminate by unimolecular (E1) mechanism, which involves rate-determining
ionization of the alkyl halide to a carbocation, followed by deprotonation of the
carbocation. If steric hindrance, i.e. with a base such as potassium tert-butoxide
in tert-butyl alcohol, inhibits the formation of the most substituted alkene, then
the least substituted alkene predominates (Hofmann products).
58‫تركيب ص‬
3- Dehalogenation of vicinal dibromides:
Vicinal dibromides (two bromines on adjacent carbon atoms) are converted to
alkenes by reduction with either iodide ion or zinc in acetic acid. This
dehalogenation is rarely an important synthetic reaction, because the most likely
origin of a vicinal dibromide is from bromination of an alkene.
58‫تركيب ص‬
De-bromination by sodium iodide takes place by the E 2 mechanism
through an anti-planar transition state. Zinc serves as reducing agent in Zn/acetic
acid dehalogenation. The actual reduction takes place at the surface of the metal
and the mechanism is uncertain.
4- Preparation of cyclopropene:
It is obtained by exhaustive methylation of cyclopropylamine followed by
distillation of the formed cyclopropyltrimethylammonium hydroxide.
59‫تركيب ص‬
General reactions of alkenes
The characteristic reaction of alkenes is addition to the double bond. The
general form of addition to an alkene may be represented as:
60‫تركيب ص‬
1- Catalytic hydrogenation of alkenes:
Hydrogenation of an alkene is formally a reduction, with H2 adding across the
double bond to give an alkane. The process usually requires a catalyst containing
finely divided Pt, Pd, or Ni.
60‫تركيب ص‬
For most alkenes, hydrogenation takes place at room temperature using
hydrogen gas at atmospheric pressure. Hydrogenation actually takes place at the
surface of the metal, where the liquid solution of the alkenes comes into contact
with hydrogen and the catalyst. Hydrogenation is an example of heterogeneous
catalysis, with the (solid) catalyst in a different phase from the reactant solution.
The two hydrogen atoms usually add from the same side of the molecule. This
mode of addition is called a syn addition.
60‫تركيب ص‬
A second stereochemical aspect of alkene hydrogenation concerns its
stereoselectivity.
61‫تركيب ص‬
The only product obtained is cis-pinane, none of the seteroisomeric transpinane being formed.
61‫تركيب ص‬
2- Addition of halogens to alkenes:
Halogens add to alkenes by electrophilic addition to form vicinal dihalides (the
two halogen atoms attached to adjacent carbons).
62‫تركيب ص‬
Addition of chlorine (Cl2) or bromine (Br2) takes place rapidly at room
temperature and below in a variety of solvents, including acetic acid, carbon
tetrachloride, chloroform and dichloromethane. Fluorine addition to alkenes is a
violent reaction, difficult to control, and accompanied by substitution of
hydrogens by fluorine. The addition of I2 to alkenes is endothermic. Vicinal
diiodides have a pronounced tendency to lose I2 and revert to alkenes.
Mechanism of reaction:
1. Reaction of ethylene and bromine to form a bromonium ion.
62‫تركيب ص‬
2. Nucleophilic attack of bromide anion on the bromination ion.
63‫تركيب ص‬
Unlike a normal carbocation, all the atoms in a halonium ion have filled octets.
The three-membered ring has considerable ring strain, however, which combines
with a positive charge on an electronegative halogen atom to make the halonium
ion strongly electrophilic. Attack by a nucleophilic, such as a halide ion, opens
the halonium ion to give a stable product. Addition of chlorine and bromine to
cycloalkenes is anti-addition.
63‫تركيب ص‬
The anti-addition of a halogen to an alkene is example stereospecific
reaction.
64‫تركيب ص‬
3- Halohydrin formation:
In aqueous solution chlorine, bromine and iodine react with alkenes to form
compounds known as vicinal halohydrins, which have halogen and hydroxyl
group on adjacent carbons.
65‫تركيب ص‬
Anti-addition is observed. The halogen and the hydroxyl group add to
opposite faces of the double bond.
65‫تركيب ص‬
Mechanism of reaction:
Step 1:
65‫تركيب ص‬
Step 2:
65‫تركيب ص‬
If the alkene is unsymmetrical, Markovinkov’s rule applies to halohydrin
formation. The positively polarized halogen adds to the carbon that has the greater
number of hydrogen substituents.
66‫تركيب ص‬
4- Addition of hydrogen halides to alkenes:
Hydrogen halides (HF, HCl, HBr, and HI) add readily to the double bond of
alkenes:
66‫تركيب ص‬
Reaction mechanism:
Step 1: (slow)
67‫تركيب ص‬
Step 2: (fast)
67‫تركيب ص‬
A hydrogen halide contains a highly polar –H-X- bond and can easily lose
H+ to the π-bond of an alkene. The result of the attack of H+ is an intermediate
carbocation, which quickly undergoes reaction with a negative halide ion to yield
an alkyl halide. Because the initial attack is by an electrophile, the addition of HX
to an alkene is called an electrophilic addition reaction. Addition of HX to an
unsymmetrically-substituted alkene could lead to either of two products, yet only
one is observed. This addition obeys Markovnikov’s rule. The original statement
of Markovnikov’s rule in the addition of HX to the double bond of alkene, the
hydrogen atom adds to the carbon atom of the double bond that already has the
greater number of hydrogen atoms.
68‫تركيب ص‬
Markovnikov’s rule (extended): in an electrophilic addition to an alkene,
the electrophilic adds in such a way as to generate the most stable intermediate.
68‫تركيب ص‬
The addition of HBr is regiospecific, because in each case only one of the
two possible orientations of additions is observed. Like HBr, both HCl and HI
add to the double bonds of alkenes, and they also follow Markovnikov’s rule.
Anti-Markovnikov’s addition of HBr:
Anti-Makovnikov products result from addition of HBr (but not HCl or HI)
in the presence of peroxides (ROOR). Peroxides give rise to free radicals that act
as catalysts to accelerate the addition causing it to occur by free-radical
mechanism. The oxygen-oxygen bond in peroxide is rather weak. It can break to
give two radicals.
Initiation:
69‫تركيب ص‬
Propagation:
69‫تركيب ص‬
The number of free-radicals is constant, until free radicals come together
and terminate the chain reaction.
Radical addition of HBr to unsymmetrical alkenes:
70‫تركيب ص‬
The electrophile in the case, Br+, adds to the less highly substituted end of
the double bond, and the radical electron appears on the more highly substituted
carbon to give the more stable free radical. This intermediate reacts with HBr to
give anti-Markovnikov product.
5- Addition of sulphuric acid to alkenes:
When alkenes are treated with cold concentrated sulphuric acid, they dissolve
because they react by addition to form alkyl hydrogen sulphates.
71‫تركيب ص‬
In the first step, the alkene accepts a proton from sulphuric acid to form a
carbocation; in the second step the carbocation reacts with a hydrogen sulphate
ion to form an alkyl hydrogen sulphate. The addition of sulphuric acid is also
regioselective and it follows Markovnikov’s rule.
72‫تركيب ص‬
Alkyl hydrogen sulphates can be easily hydrolysed to alcohols by heating them
with water.
72‫تركيب ص‬
6- Acid-catalysed hydration of alkenes:
Another method by which alkenes may be converted to alcohols is through the
addition of a molecule of water across the carbon-carbon double bond under
conditions of acid catalysis.
73‫تركيب ص‬
Unlike the addition of concentrated sulphuric acid to form alkyl hydrogen
sulphates, this reaction is carried out in a dilute acid medium. A 50% watersulphuric acid solution is often used, yielding the alcohol directly without the
necessity of a separate hydrolysis step. Markovnikov’s rule is followed: a proton
adds to one carbon of the double bond and a hydroxyl group adds to the other.
73‫تركيب ص‬
Reaction mechanism
Step 1: Protonation of carbon-carbon double bond in the direction that leads to
the more stable carbocation:
74‫تركيب ص‬
Step 2: Water acts as a nucleophile to capture tert-butyl cation:
74‫تركيب ص‬
Step 3: Deprotonation of tert-butyloxonium ion. Water acts as Bronsted base:
74‫تركيب ص‬
One complication associated with alkene hydration is the occurrence of
rearrangement. Because the reaction involves the formation of a carbocation in
the first step, the carbocation formed initially invariably rearranges to a more
stable one if such a rearrangement is possible.
7- Oxymercuration-demercuration of alkenes:
This is another method for converting alkenes to alcohols with Markovnikov’s
orientation, but with the advantage that rearrangements of the carbon skeleton do
not occur. The reagent for mercuration is mercuric acetate Hg(OCOCH3)2,
abbreviated Hg(OAc)2.
75‫تركيب ص‬
Reaction mechanism
The first step: oxymercuration involves an electrophilic attack on the
double bond by the positively charged mercury species. The product is a
mercurinium ion, an organometallic cation containing a three-membered ring.
Carbocation of this type are relatively stable, formed readily and don’t rearrange.
Mercuration commonly takes place in a solution containing water and an organic
solvent (tetrahydrofuran) to dissolve the alkene. Attack on the mercurinium ion
by water gives (after deprotonation) an organomercurial alcohol.
76‫تركيب ص‬
The second step: Demercuration to form alcohol, sodium borohydride (NaBH4),
a reducing agent, replaces the mercuric acetate fragment with hydrogen.
76‫تركيب ص‬
Oxymercuration-memercuration of an unsymmetrical alkene generally
gives Markovnikov orientation of addition.
77‫تركيب ص‬
In oxymercuration-demercuration reaction of cyclopentene, the attack by
water on the mercurinium ion comes from the opposite side of the ring, resulting
in addition of the hydroxyl group and the mercury atom to opposite sides of the
ring (Anti-addition).
77‫تركيب ص‬
8- Hydroboration-oxidation of alkenes:
Diborane (B2H6) is a dimer composed of two molecules of borane (BH3).
Hydroboration reactions are usually carried out in ethers, either diethyl ether
(C2H5)2O, or in some higher molecular weight ethers such as “diglyme”
(CH3OCH2CH2)2O. Borane undergoes rapid and quantitative reaction with most
alkenes to form organoboranes (R3B). The Overall reaction is the result of three
separate reaction steps. In each step, one alkyl group is added to borane until all
three hydrogen atoms have been replaced by alkyl groups. This sequence of
reactions is called hydroboration.
78‫تركيب ص‬
Following hydroboration, the organoborane is oxidized by treatment with
hydrogen peroxide in aqueous base. This is the oxidation stage.
𝐻2 𝑂2 / 𝑂𝐻 −
(𝐶𝐻3 𝐶𝐻2 )3 𝐵 →
Triethylborane
3 𝐶𝐻3 𝐶𝐻2 𝑂𝐻
Ethyl alcohol
Borane is different from the other addition reagents because H is
electronegative portion of the molecule, when borane adds to a double bond, the
hydrogen (as a hydride ion, H-) becomes bonded to the more substituted carbon,
resulting in anti-Markovnikov addition.
79‫تركيب ص‬
Stereochemistry of hydroboration:
When borane adds to a double bond, the boron atom and the hydride ion
become bonded to the two carbon atoms of the double bond simultaneously. The
result is that B and H must be added to the same side of the double bond, i.e. cisaddition, or syn-addition.
80‫تركيب ص‬
Hydroboration of alkenes is a stereospecific reaction where a particular
stereoisomer of the starting compound reacts to give just one stereoisomer [or (±)
pair] of the product. When an organoborane is subsequently oxidized to an
alcohol, the hydroxyl group ends up in the same position as the boron atom that
is replaced, that is, with retention of configuration at that carbon. The reason that
the configuration is retained is that the oxidation proceeds by a 1,2-shift (similar
in some respects to a carbocation rearrangement), followed by hydrolysis of the
B-O bond to yield the alcohol. The RO is not affected in this hydrolysis.
81‫تركيب ص‬
9- Addition of carbenes to alkenes: (refer to cycloalkanes)
Methylene (:CH2) is the simplest of the carbenes: uncharged reactive
intermediates that have a carbon atom with two bonds and two nonbonding
electrons. Like borane (BH3), methylene is a potent electrophile because it has an
unfilled octet. It adds to the electron rich π-bond of an alkene to form a
cyclopropane. This reaction is a stereospecific syn-addition, thus cis alkenes yield
cis cyclopropenes, and trans alkenes yield trans cyclopropanes.
82‫تركيب ص‬
Methylene can be prepared by the decomposition of diazomethane
(CH2N2) by heating or photolysis.
82‫تركيب ص‬
There are two difficulties with using diazomethane in the preparation of
cyclopropane:
i)
It is extremely toxic and explosive.
ii)
Methylene generated from diazomethane is so reactive that it inserts
into C-H bonds as well as C=C bonds and several side products are
obtained.
Dihalocarbenes are frequently employed in the synthesis of cyclopropane
derivatives from alkenes. Most reactions of dihalocarbenes are stereospecific (if
the R groups of the alkene are trans, they will be trans in the product.
83‫تركيب ص‬
Dichlorocarbene can be synthesized by the α-elimination of the elements
of hydrogen chloride from chloroform.
84‫تركيب ص‬
Cyclopropanes may be synthesized by another reaction involving
organozinc reagents. This reaction is called the Simmons Smith reaction. The
Simmons-Smith reagent is made by adding methylene iodide to the “zinc-copper
couple”, zinc dust that has been activated with an impurity of copper. The reagent
probably resembles iodomethylzinc iodide, ICH2ZnI. This kind of reagent is
called Carbenoid because it reacts much like a carbene but it does not actually
contain a divalent carbon atom.
85‫تركيب ص‬
10- Syn-hydroxylation of alkenes:
Hydroxylation is the addition of hydroxyl group to each end of the double bond.
The most common reagents are: Osmium tetroxide and potassium permanganate.
85‫تركيب ص‬
Osmium tetroxide hydroxylation
Osmium tetroxide (OsO4, sometimes called osmic acid) reacts with alkenes
to form a cyclic osmate ester. Hydrogen peroxide hydrolyses the osmate ester and
reoxidizes osmium to osmium tetroxide. The regenerated osmium tetroxide
catalyst continues to hydroxylate more molecules of the alkene.
86‫تركيب ص‬
Because the two carbon-oxygen bonds are formed simultaneously with the
cyclic osmate ester, the oxygen atoms add to the same face of the double bond,
i.e. with syn stereochemistry.
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Permanganate hydroxylation
Osmium tetroxide is expensive, highly toxic, and volatile. A cold, dilute
solution of potassium permanganate also hydroxylates alkenes with syn
stereochemistry, and slightly reduced yields in most cases.
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In addition to its synthetic value, the permanganate oxidation of alkenes
provides a simple chemical test for the presence of an alkene. The purple colour
of potassium permanganate changes quickly to brown precipitate of MnO2.
11- Oxidative cleavage of alkenes:
In the potassium permanganate hydroxylation, if the solution is warm or acidic
or too concentrated, oxidative cleavage of the glycol may occur. Mixtures of
ketones and carboxylic acids are formed, depending on whether there are any
oxidizable aldehydic C-H bonds in the initial fragments.
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Under these vigorous oxidizing conditions, the carbon of a terminal double
bond is oxidized to CO2.
88‫تركيب ص‬
12- Ozonolysis:
Like permanganate, ozone cleaves double bonds to give ketones and aldehydes.
However, ozonolysis is milder, and both ketones and aldehydes can be recovered
without further oxidation.
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Ozone has excess energy over oxygen, and it is much more reactive. A
Lewis structure of ozone shows that the central oxygen atom bears a positive
charge, and each of the outer oxygen atom bears a negative charge.
89‫تركيب ص‬
Ozone reacts with an alkene to form a cyclic compound called a primary
ozonide molozonide. The molozonide has two peroxy (-O-O-) linkages, and it is
quite unstable. It rearranges rapidly, even at low temperature, to form an ozonide.
90‫تركيب ص‬
Ozonides are very stable, and they are rarely isolated. In most cases they
are immediately reduced by mild reducing agent such as dimethyl sulfoxide or
zinc and water. The products of this reduction are ketones and aldehydes.
90‫تركيب ص‬
One of the most common uses of ozonolysis is for determining the position
of double bonds in alkenes.
13- Polymerization of alkenes:
Polymers are compounds that consist of very large molecules made up of many
repeating subunits called monomers, and the reactions by which monomers are
joined together are called polymerization reactions. The addition reactions occur
through radical, cationic or anionic mechanisms depending on how they are
initiated.
a) Radical polymerization
The polymerization is started by a catalyst or an initiator such as O2 or a peroxide.
91‫تركيب ص‬
b) Cationic polymerization
The reaction proceeds through a carbocation intermediate in the presence of a
Lewis acid as a catalyst, e.g. BF3 (Sulphuric acid usually produces dimers instead
of polymers).
92‫تركيب ص‬
c) Anionic polymerization
Alkenes containing electron-withdrawing groups polymerize in the presence of
strong base.
92‫تركيب ص‬
Examples:
92‫تركيب ص‬
II-
Alkynes
Alkynes are hydrocarbons characterized by the presence of a carbon-carbon triple
bond. Non-cyclic alkynes have the molecular formula CnH2n-2. Acetylene
(𝐻𝐶 ≡ 𝐶𝐻) is the simplest alkynes. The compounds that have their triple bond at
the end of the carbon chain (𝑅𝐶 ≡ 𝐶𝐻) are known as mono-substituted, or
terminal alkynes. Di-substituted alkynes (𝑅𝐶 ≡ 𝐶𝑅) are said to have internal
triple bonds.
Nomenclature of alkynes
IUPAC names:
The IUPAC nomenclature for alkynes is similar to that for alkenes. We
find the longest continuous chain of carbon atoms that includes the triple bond
and change the –ane ending of the parent alkane to –yne. The chain is numbered
from the end closest to the triple bond, and the position of the triple bond is
designated by its lower-numbered carbon atom. Substituents are given numbers
to indicate their locations.
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Common names:
The common names of alkynes describe them as derivatives of acetylene.
Most alkynes can be named as a molecule of acetylene with one or two alkyl
substituents.
Structure and bonding in alkynes
Acetylene is a linear molecule with a carbon-carbon bond distance of 120
pm and carbon-hydrogen bond distances of 106 pm.
Both bonds are shorter than the corresponding bonds in ethane and in
ethane.
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The carbon-carbon triple bond in alkynes is composed of a σ and two π
bonds. The triply bonded carbons are sp hybridized. The σ component of the triple
bond contains two electrons in an orbital generated by the overlap of sp
hybridized orbitals on adjacent carbons. Each of these carbons has 2p orbitals,
which overlap in pairs so as to give two π orbitals, each of which contains two
electrons.
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Cycloalkynes
The linear geometry of the alkyne structural unit limits stable cycloalkynes
to structures in which the ring has at least nine carbon atom (sufficient size to
accommodate a linear 𝐶 − 𝐶 ≡ 𝐶 − 𝐶 unit.
Cyclononyne is the smallest one stable enough to be stored for extended
periods of time at room temperature.
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Cyclooctyne and cycloheptyne are quite strained and react rapidly with
themselves to form polymers soon after they are isolated. Cyclohexyne and even
cyclopentyne are formed as transitory intermediates in certain chemical reactions,
but neither has been isolated as a stable compound.
Physical properties of alkynes
The physical properties of alkynes are similar to those of alkanes and
alkenes. Alkynes are relatively non polar, nearly soluble in water. They are quite
soluble in most organic solvents. Alkynes generally have slightly higher boiling
points than the corresponding alkanes and alkenes.
Acidity of acetylene and terminal alkynes
Terminal alkynes are much more acidic than other hydrocarbons. Removal
of an acetylinic proton forms an acetylide ion.
The acidity of an acetylenic hydrogen stems from the nature of the sp
hybrid ≡ 𝐶 − 𝐻 bond. The acidity of a C-H bond varies with its hybridization,
increasing a character of orbitals: sp3 < sp2 < sp. The acetylenic proton is about
1019 times as acidic as a vinyl proton. When an acetylenic proton is abstracted,
the resulting carbon ion has the lone pair of electrons in the sp hybrid orbital.
Electrons in this orbital are close to the nucleus, and there is less charge separation
than in carbanions can be deprotonated by the amide (NH 2-) ion, but nor by an
alkoxide ion.
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Formation of acetylide ions
Unlike alkanes and alkenes, terminal acetylenes are easily deprotonated to
form carbanions called acetylide ions (or alkynide ions). The acetylenic proton is
removed by a very strong base, such as Grignard or organolithium reagent.
Hydroxide ions and alkoxide ions are not strong enough bases to deprotonate
alkynes internal alkynes do not have acetylenic protons, so they do not react.
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Silver (I) and copper (I) salts react with terminal alkynes to form silver and
copper acetylides. Silver and copper acetylides, are bonded more covalently than
other acetylides, however, and they are much less basic and less nucleophilic.
Silver and copper acetylides are not very soluble; they form characteristic
precipitates. This reaction provides a simple chemical test for terminal alkynes.
99‫تركيب ص‬
General methods of preparation
1- Alkylation of acetylide ions:
As acetylide ion is a strong base and a powerful nucleophile. It can displace a
halide or to sylate ion from a suitable substrate, giving substituted acetylene. To
produce a good yield, the alkyl halide in this SN2 reaction must be primary, with
no bulky substituents or branches close to the reaction center.
100‫تركيب ص‬
If the back-side approach is hindered, the acetylide ion may abstract a
proton, giving elimination by the E2 mechanism.
100‫تركيب ص‬
2- Addition of acetylide ions to carbonyl groups and epoxides:
Acetylide ion reacts like Grignard and organolithium reagents, to give primary,
secondary and tertiary acetylinic alcohols.
a) Reaction with aldehydes and ketones:
101‫تركيب ص‬
b) Reaction with epoxides:
101‫تركيب ص‬
3- Double dehydrohalogenation of alkyl dihalides:
Dehydrohalogenation of a germinal or vicinal dihalide gives a vinyl halide. Under
strongly basic conditions, a second dehydrohalogenation may occur to form an
alkyne.
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The strongly basic condition used is molten KOH in a sealed tube, usually
heated to 200oc. Sodium amide, which is stronger base than hydroxide, is also
used but at lower temperature. Unfortunately, the double dehydrohalogenation
cannot survive to any functional groups that are sensitive to strong bases. Also
the alkyne products may rearrange under these extremely basic conditions, to the
most stable alkyne isomer (the most highly substituted triple bond). Isomerization
also results when sodium amide is used, all possible triple-bond isomers are
formed, but sodium amide deprotonates the terminal acetylene. When water is
added, the acetylide ion is protonated to give the terminal alkyne.
103‫تركيب ص‬
General reactions of alkynes
1- Addition of hydrogen to alkynes:
In the presence of suitable catalyst, such as platinum, palladium and nickel,
hydrogen adds to an alkyne, reducing it to an alkane.
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Catalytic hydrogenation takes place in two steps, with an alkene
intermediate. With efficient catalysts such as Pt, Pd or Ni, it is usually impossible
to stop the reduction at the alkene stage.
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Hydrogenation of al alkyne can be stopped at the alkene stage by using
Lindlar’s catalyst (it is a poisoned palladium catalyst, composed of powdered
barium sulphate coated with palladium poisoned with quinoline).
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The catalytic hydrogenation of alkynes is similar to the hydrogenation of
alkenes, and both proceed with syn stereochemistry. Sodium metal in liquid
ammonia reduces alkynes with anti-stereochemistry, and this reduction is used to
convert alkynes to trans alkenes.
2- Addition of halogens:
Bromine and chlorine add to alkynes just as they held to alkenes. If 1 mole of
halogen adds to an alkyne, the product is a dihaloalkene. The stereochemistry of
addition may be either syn or anti, and the products are often mixtures of cis and
trans isomers. If 2 moles of halogen add to an alkyne, a tetrahalide results.
105‫تركيب ص‬
3- Addition of hydrogen halides:
Hydrogen halides add across the triple bond of an alkyne in much the same way
they add across the alkene double bond. The initial product is vinyl halide. When
a hydrogen halide adds to a terminal alkyne, the product has the orientation
predicted by Markovnikov’s rule. A second molecule of HX can add, usually with
the same orientation as the first and lead to a germinal dihalide. In an internal
alkyne, the acetylinic carbon atoms are equally substituted and a mixture of
products results.
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The mechanism is similar to the mechanism of hydrogen halide addition to
alkenes.
107‫تركيب ص‬
The effect of peroxides on addition of HBr to alkene is also seen with
alkynes: Peroxides catalyse the addition of HBr to alkynes in the antiMarkovnikov’s direction.
107‫تركيب ص‬
4- Hydration of alkynes:
a) Mercuric ion-catalysed hydration
Alkynes undergo acid catalysed addition of water across the triple bond in the
presence of mercuric ion as catalyst. A mixture of mercuric sulphate in aqueous
sulphuric acid is commonly used as the reagent. The hydration of alkynes is
similar to hydration of alkenes, and it also goes with Markovnikov orientation.
108‫تركيب ص‬
Reaction mechanism
108‫تركيب ص‬
Electrophilic addition of mercuric ion gives a vinyl cation, which reacts
with water and loses a proton to give an organomercurial alcohol under the acidic
reaction conditions; mercury is replaced by hydrogen to give a vinyl alcohol,
called al enol. Enols tend to be unstable, and isomerize to the more stable keto
form. This type of rapid equilibrium is called the keto-enol tautomerism.
b) Hydroboration-oxidation
Hydroboration-oxidation adds water across the double bonds of alkenes with antiMarkovnikov orientation. A similar reaction takes place with alkynes, except that
a hindered dialkylboran must be used to prevent addition of two molecules of
borane across the triple bond. Di (secondary isoamylborane called
“disiamylborane”), adds to the triple bond only once to give a vinyl borane. In a
terminal alkyne, the boron atom bonds to the terminal carbon atom.
110‫تركيب ص‬
Oxidation of the vinyl borane (using basic hydrogen peroxide) gives a
vinyl alcohol (enol) resulting from anti-Markovnikov addition of water across the
triple bond. This enol quickly tautomerizes to its more stable carbonyl (keto)
form.
5- Oxidation of alkynes:
If an alkyne is treated with aqueous potassium permanganate under nearly neutral
conditions, an α-diketone results.
111‫تركيب ص‬
If the reaction mixture becomes warm or two basic, the diketone undergoes
oxidative cleavage. The products are the salts of carboxylic acids, which can be
converted to the free acids by adding dilute acid. Terminal alkynes are cleaved
similarly to give carboxylic acid and CO2.
111‫تركيب ص‬
6- Ozonolysis
Ozonolysis of an alkyne, followed by hydrolysis, gives products similar to those
from oxidative cleavage by permanganate. Either cleavage can be used to
determine the position of the triple bond in an unknown alkyne.
111‫تركيب ص‬
Chapter 2
Aliphatic Halogen Compounds
Aliphatic hydrogen compounds include: alkyl halides, vinyl halides and
allyl halides.
C2H5Br
CH2=CHCl
CH2=CH-CH2Cl
Ethyl bromide
Vinyl chloride
Allyl chloride
“an alkyl halide”
“a vinyl halide”
“an allyl halide”
A- Alkyl Halides
Alkyl halides have the general formula RX, where R is an alkyl or substituted
alkyl group and X is any halogen atom (F, Cl, Br, or I).
I-
Monohaloalkanes: CnH2n+1X
Alkyl halides are classified according to the nature of the carbon atom bonded to
the halogen into:
1) Primary alkyl halides: if the halogen-bearing carbon is bonded to one
carbon atom, RCH2X, 1o.
2) Secondary alkyl halides: if the halogen-bearing carbon is bonded to two
carbon atoms R2CHX, 2o.
3) Tertiary alkyl halides: if the halogen-bearing carbon is bonded to three
carbon atoms, R3CX, 3o.
113‫تركيب ص‬
II-
The dihalogenated compounds: are subdivided into:
1) Germinal diahl
Ides: “alkylidene dihalides”. They have the two halogen atoms
bonded to the same carbon atom.
2) Vicinal dihalides: “alkylene dihalides”. They have the two halogens
bonded to adjacent carbon atoms.
113‫تركيب ص‬
3) α, ώ-Dihalides: “polymethylene dihalides”
The two halogens are attached to both ends of a carbon chain.
III-
Polyhalogenated alkyl halides:
114‫تركيب ص‬
Nomenclature of alkyl halides
There are two ways of naming alkyl halides:
1) IUPAC system: the alkyl halides are named as an alkane with a halosubstituent: fluorine is fluoro-, chlorine is chloro-, bromine is bromo-, and
iodine is iodo-. The result si a systematic halo alkane names, as 1chlorobutane.
2) Common or trivial names: these are constructed by naming the alkyl
group and then the halide as in “isopropyl bromide”. This is the origin of
the term alkyl halide.
Structure of alkyl halides
In an alkyl halide, the halogen atom is bonded to sp 3 hybrid carbon atom.
The halogen is more electronegative than carbon and the C-X bond is polarized
with a partial negative charge on the halogen.
115‫تركيب ص‬
The electronegativity of the halogen decrease in the order: F > Cl > Br > I.
The carbon-halogen bond length increases as the halogen atoms become bigger
(large atomic radii) in the order: C-F < C-Cl < C-Br < C-I. The overall result is
that the bond dipole moments decrease in the order: C-Cl > C-F > C-Br > C-I (the
dipole moment μ is 1.56, 1.51, 1.48 and 1.29 D respectively). A molecular dipole
moment is the vector sum of the individual bond dipole moments. The four
symmetrically oriented polar bonds of the carbon tetrahalides cancel to give the
molecular dipole moment of zero.
115‫تركيب ص‬
Physical character of alkyl halides
Boiling points and densities of several halogenated alkanes are listed in the
table below. Except for fluorine, halogen atoms are heavy compared to carbon or
hydrogen atoms. The increase in molecular weight and increase in polarizability
(leading to increased van der Waals attractions) as halogen atoms are substituted
into hydrocarbon molecules cause an increase in the boiling points.
I > Br > Cl > F
atomic weight of the halogens
In case of isomeric alkyl halides, the n-alkyl halides have the greatest
boiling points.
B.P.:
CH3(CH2)3Cl >
(CH3)2CHCH2Cl >
(CH3)3CCl
n-butyl chloride
Isobutyl chloride
tert-butyl chloride
78oc
69oc
51oc
Generally, the boiling point of primary alkyl halides is greater than that of
tertiary alkyl halide.
Physical properties of some halogenated alkanes:
Trivial name
Formula
Bp, oc
Density G/ml at 20oc
Methyl chloride
CH3Cl
24
Gas
Methylene chloride
CH2Cl2
40
1.34
Chloroform
CHCl3
61
1.49
Carbon tetrachloride
CCl4
77
1.60
Methyl bromide
CH3Br
5
Gas
Methyl iodide
CH3I
43
2.28
Again, because of the mass of a halogen atom, the densities of liquid alkyl
halides are often greater than those of other comparable organic compounds.
Many common halogenated solvents, such as chloroform or dichloromethane are
denser than water (densities greater than 1.0 g/ml). alkyl fluorides and alkyl
chlorides (those with one chlorine atom) are less dense than water. Halogenated
hydrocarbons do not form strong hydrogen bonds with water and thus are
insoluble in water.
Preparation of alkyl halides:
1) From alkanes: Free radical halogenation (refer to alkanes)
Free radical halogenation is rarely effective method for the synthesis of alkyl
halides. It usually produces mixtures of products, because there are different
kinds of hydrogen atoms that can be abstracted, also more than one halogen atom
may react giving multiple substitution.
117‫تركيب ص‬
Free radical bromination is exceptionally highly selective, and it gives
good yields with alkanes that have one type of hydrogen atom that is more
reactive than the others.
118‫تركيب ص‬
2) From alcohols:
Alcohols react with halogenating agents like hydrogen halides (HX), phosphorus
halides (PX3 or PX5) (X = I, Br, Cl) or thionyl chloride (SOCl2).
𝐻2 𝑆𝑂4 . 𝐻𝑒𝑎𝑡
𝐶𝐻3 𝐶𝐻2 𝐶𝐻2 𝑂𝐻 + 𝐻𝐼 →
𝐶𝐻3 𝐶𝐻2 𝐶𝐻2 𝐼 + 𝐻2 𝑂
3 𝐶𝐻3 𝐶𝐻2 𝑂𝐻 + 𝑃𝐼3 ⟶ 3 𝐶𝐻3 𝐶𝐻2 𝐼 + 𝐻3 𝑃𝑂3
(red P + I2)
phosphoric acid
(𝐶𝐻3 )2 𝐶𝐻𝐶𝐻2 𝑂𝐻 + 𝑆𝑂𝐶𝑙2 ⟶ (𝐶𝐻3 )2 𝐶𝐻𝐶𝐻2 𝐶𝑙 + 𝐻𝐶𝑙 ↑ +𝑆𝑂2 ↑
Inversion of configuration
119‫تركيب ص‬
Retention of configuration
119‫تركيب ص‬
3) From alkenes and alkynes: (refer to addition of X2 or HX to alkene &
alkynes).
120‫تركيب ص‬
4) Allylic bromination or chlorination:
𝐶𝑙2 . 𝑙𝑖𝑔ℎ𝑡
𝐶𝐻2 = 𝐶𝐻 − 𝐶𝐻3 →
𝐶𝐻2 = 𝐶𝐻 − 𝐶𝐻2 𝐶𝑙
Allyl chloride
There are 3 allylic hydrogens, which are much more reactive than the inert vinylic
hydrogens on the double bonded carbons.
Bromination of cyclohexene gives a good yield of 3-bromocyclohexene,
where bromine has substituted for an allylic hydrogen.
121‫تركيب ص‬
This selective allylic bromination occurs because the allylic intermediate
is resonance-stabilized. Abstraction of an allylic hydrogen atom gives a
resonance-stabilized allylic radical. This radical reacts with Br2 regenerating a
bromine radical.
121‫تركيب ص‬
A large excess of bromine must be avoided, because bromine can add to
the double bond. N-bromosuccinimide (NBS) is often used as the bromine source
in free-radical bromination, because it combines with the HBr side product to
regenerate a nearly constant low concentration of bromine.
122‫تركيب ص‬
5) Hunsdiecker reaction:
The basis of this reaction is the decarboxylative halogenation of carboxylic acid.
The reaction converts heavy metal salts of carboxylic aids to alkyl halides with
the loss of one carbon atom.
122‫تركيب ص‬
The Hunsdiecker reaction is usually carried out by treating the carboxylic
acid with a heavy metal base such as Ag2O, HgO, or Pb(OAc)4 to form the heavymetal salt. Bromine or iodine is added, and the reaction mixture is heated. This
reaction forms the metal halide together with an acyl hypobromite (or an acyl
hypoiodite), which dissociates into radicals on heating. Although most
carboxylate anions are quite stable, radicals decarboxylates by losing CO 2,
leaving alkyl radicals which initiate the free radical reaction.
123‫تركيب ص‬
1- Initiation step:
123‫تركيب ص‬
2- Propagation step:
123‫تركيب ص‬
General reactions of alkyl halides
1) Nucleophilic substitution reactions SN1 and SN2.
2) Elimination reactions (E1 and E2).
3) Organometallic reactions.
4) Reduction.
5) Coupling reactions (see synthesis of alkanes).
1. SN1 and SN2 mechanisms:
The two major mechanisms or nucleophilic substitution are outlined in the
following table:
SN1
Steps
SN2
Two steps:
One step:
1) RX R+ + X¬
124‫تركيب ص‬
2) R+ + Nu RNu
Nucleophile
Nucleophile
strength
are Strong nucleophiles are needed
unimportant (weak nucleophile)
Rate
= K[RX] (1st order)
= K[RX][Nu¬] (2nd order)
Molecularity
Unimolecular
Bimolecular
Stereochemistry
Retention and racenization
Inversion,
back
side
attack
stereospecific
Reactivity
3o > 2o
CH3X > 1o > 2o
structure of R
1o and CH3X are not suitable
3o is not suitable
Determining
Stability of R+
Steric hindrance in R group
factor
Nature of leaving Good one required RI > RBr > Good one required RI > RBr > RCl >
group
RCl > RF
RF
a- On rate
Good ionizing solvent required
Rate increases in less polar solvents
b- On
R+ reacts with nucleophilic Rate depends on nucleophilicity I¬ >
Solvent effects:
nucleophile solvents rather than with Nu¬ Br¬ > Cl¬; RS¬ > RO¬ equilibrium lies
(solvolysis), except when R+ is towards weak Bronsted base
relatively stable
Catalysis
Lewis acids, as AlCl3 or ZnCl2,
1- Aprotic polar solvent.
or Ag+
2- Phase-transfer.
Competition
Elimination, rearrangement are Elimination, especially with 3o RX in
reaction
common
strong Bronsted base, rearrangement
not possible
Examples of nucleophilic substitution reactions:
a) Alcohol formation:
125‫تركيب ص‬
b) Halide exchange:
𝑅 − 𝑋 + 𝐼− ⟶ 𝑅 − 𝐼 + 𝑋 −
18−𝑐𝑟𝑜𝑤𝑛−6 . 𝐶𝐻3 𝐶𝑁
𝑅 − 𝐶𝑙 + 𝐾𝐹 →
𝑅 − 𝐹 + 𝐾𝐶𝑙
c) Williamson ether synthesis:
𝑅−𝑋
𝑅𝑂− ⟶ 𝑅 − 𝑂 − 𝑅 + 𝑋 −
+
Alkyl halide
alkoxide
ether
𝑅 − 𝑋 + 𝑅𝑆 − ⟶ 𝑅 − 𝑆 − 𝑅 + 𝑋 −
Thioester
d) Amine synthesis:
𝑁𝐻3 𝑒𝑥𝑐𝑒𝑠𝑠 +
𝑅−𝑋→
𝑁𝐻3
𝑅 − 𝑁𝐻3 𝑋 − →
𝑅 − 𝑁𝐻2 + 𝑁𝐻4 𝑋 −
e) Nitrile synthesis:
𝑅 − 𝑋 + 𝐶 ≡ 𝑁 ⟶ 𝑅 − 𝐶 ≡ 𝑁 + 𝑋−
f) Higher alkynes formation:
𝑅 − 𝑋 + 𝐶𝐻 ≡ 𝐶−⟶ 𝑅 − 𝐶 ≡ 𝐶 − +𝑋 −
2. Elimination reactions (E1 and E2):
The E1 mechanism is a two-step mechanism: carbocation is formed in the first
step and in the second one abstraction of a proton by the base converts the
carbocation into an alkene.
127‫تركيب ص‬
E1
E2
Steps
Two steps
One step
Kinetics
First order
Second order
Rate = K [RX]
Rate = K [RX][B]
Ionization
determines
rat Bimolecular
unimolecular
Orientation
Most highly substituted alkene
Stereochemistry Non stereospecific
Most highly substituted alkene
Stereospecific
No particular geometry required Anti-elimination, co-planar (syn
for the slow step
Reactivity order 3o > 2o > 1o Rx
factor
Stability of r+
when anti impossible)
3o > 2o > 1o Rx
Stability of alkenes (Saytzeff rule)
Rearrangements Common
None
Competing
SN2
SN1, SN2
reaction
Regioselectivity Saytzeff factors E1
Favours E2
Alkyl group
3o > 2o > 1o
3o > 2o > 1o
Loss of H
No effect
Increased acidity
Base strength
Weak
Strong base are required
Concentration
Low
High
Catalysis
Ag+
Phase-transfer
Solvent
Good ionizing solvent required
Solvent polarity is not so important
Elimination reaction:
a) Dehydrohalogenation
129‫تركيب ص‬
E2 elimination of cyclohexane requires that the proton and the leaving group both
be in trans-diaxialrelationship.
129‫تركيب ص‬
b) Dehalogenation
129‫تركيب ص‬
Chapter 3
Alcohols & Thiols
A- Alcohols
They are organic compounds containing hydroxyl (¬OH) group. One way of
organizing the alcohol family is to classify each alcohol according to the type of
carbinol carbon atom (the one bonded to the ¬OH group). If this carbon atom is
primary, the compound is a primary alcohol. A secondary alcohol has the ¬OH
group attached to a secondary carbon atom, and a tertiary alcohol has it bonded
to a tertiary carbon atom.
Nomenclature of alcohols
130‫تركيب ص‬
Common name
The common name of an alcohol is derived from the common name of the
alkyl group and the word alcohol.
𝐶𝐻3 − 𝑂𝐻
𝐶𝐻3 𝐶𝐻2 𝐶𝐻2 − 𝑂𝐻
Methyl alcohol
n-propyl alcohol
𝐻3 𝐶∖
𝐻3 𝐶
𝐶𝐻2 = 𝐶𝐻 − 𝐶𝐻2 − 𝑂𝐻
∕ 𝐶𝐻 − 𝑂𝐻
Isopropyl alcohol
Allyl alcohol
IUPAC name
The IUPAC name of alcohol is taken from the names of the parent alkanes,
but with the ending –ol. Cyclic alcohols are named using the prefix cyclo-: the
hydroxyl group is assumed to be on C1.
131‫تراكيب ص‬
Alcohols with two ¬OH groups are called diols or glycols. They are named
like other alcohols except that the suffix diol is used.
Solubility properties of alcohols
Alcohols form hydrogen bonds with water, and several of the lower
molecular weight alcohols are miscible with water. The hydroxyl group is
hydrophilic because of its affinity for water and other polar substances.
Acidity of alcohols
The hydroxyl proton of an alcohol is weakly acidic. A strong base can
remove the hydroxyl proton to give an alkoxide ion. Because the alkoxide ions
are stronger bases than hydroxides, their formation necessitates the use of bases
stronger than the alkoxide themselves. Sodamide and Grignard reagents are
enough bases to abstract hydrogen from an alcohol. A metal hydride (NaH or KH)
can also be used.
𝑅𝑂𝐻 + 𝑁𝑎𝑁𝐻2 → 𝑅𝑂− + 𝑁𝐻3
𝑅𝑂𝐻 + 𝑅. 𝑀𝑔𝑋 → 𝑅𝑂− +𝑀𝑔𝑋 + 𝑅. 𝐻
The most convenient method for the preparation of alkoxides is the
treatment of an alcohol with an alkali metal such as Na or K. This reaction is an
oxidation-reduction.
2 𝐶𝐻3 𝑂𝐻 + 2𝑁𝑎 → 2 𝑅𝑂− +𝑁𝑎 + 𝐻2
Sodium methoxide
Synthesis of alcohols
1- Synthesis from alkenes:
2- Synthesis from alkyl halides:
133‫تركيب ص‬
3- Synthesis from Grignard reagents:
Grignard reagents serve as the nucleophile in the addition to a carbonyl group.
The Grignard reagent adds to the carbonyl group to form an alkoxide ion.
Addition of an acid, protonates the alkoxide to give the alcohol.
134‫تركيب ص‬
Acid chlorides and esters react with two equivalents of Grignard reagents
to give tertiary alcohols.
135‫تركيب ص‬
Grignard reagents usually do not react with ethers, but epoxides are
reactive because of their ring strain. Ethylene oxide (oxirane) reacts with
Grignard reagents to give, after protonation, primary alcohols.
136‫تركيب ص‬
4- Synthesis by metal hydride reduction of carbonyl group:
a- Sodium borohydride:
136‫تركيب ص‬
b- Lithium aluminium hydride:
136‫تركيب ص‬
c- Catalytic hydrogenation of ketones and aldehydes:
136‫تركيب ص‬
Reactions of alcohols
1- Oxidation of alcohols:
a- Oxidation of secondary alcohols:
Secondary alcohols are easily oxidized to give excellent yields of ketones. The
chromic acid reagent is often best for laboratory oxidation of secondary alcohols.
137‫تركيب ص‬
b- Oxidation of primary alcohols:
Oxidation of a primary alcohols forms an aldehyde. An aldehyde is easily
oxidized further to give a carboxylic acid.
137‫تركيب ص‬
A better reagent for the limited oxidation of primary alcohols to aldehydes
is pyridinium chlotochromate (PCC).
138‫تركيب ص‬
Tertiary alcohols have no hydrogen atoms of the carbinol carbon atom, and
oxidation must take place by breaking carbon-carbon bonds. Such oxidation
requires severe conditions and results in mixtures of products.
2- Reduction of alcohols:
A general method for reducing an alcohol involves converting the alcohol to the
tosylate ester, then using a hydride reducing agent to displace the tosylate-leaving
group.
138‫تركيب ص‬
Tosylate esters are easily made from alcohols in very high yields, often
with tosyl chloride as the reagent and pyridine as the solvent. The tosylate group
is an excellent leaving group and alkyl tosylates undergo substitution and
elimination.
139‫تركيب ص‬
3- Reactions of alcohols with hydrohalic acids:
Concentrated hydrobromic acid rapidly converts tert-butyl alcohol to tert-butyl
bromide. The strong acid protonates the hydroxyl group, converting it to a good
leaving group.
140 ،139‫تركيب ص‬
Hydrochloric acid (HCl) reacts with alcohols in the same way that
hydrobromic acid does. For example, concentrated aqueous HCl reacts with tertbutyl alcohol to give tert-butyl chloride.
(𝐶𝐻3 )3 𝐶 − 𝑂𝐻 + 𝐻𝐶𝑙 / 𝐻2 𝑂 → (𝐶𝐻3 )3 𝐶 − 𝐶𝑙 + 𝐻2 𝑂
t-butyl alcohol
t-butyl chloride (98%)
Chloride ion is a weaker nucleophile than bromide ion, because it is smaller
and less polarizable. An additional Lewis acid, such as zinc chloride (ZnCl 2), is
sometimes necessary to promote the reaction of HCl with primary and secondary
alcohols. Zinc chloride coordinates with the oxygen of the alcohol in the same
way a proton does except that zinc chloride coordinates more strongly. The
reagent composed of HCl and ZnCl2 is called the Lucas reagent. Secondary and
tertiary alcohols react with the Lucas reagent by the S N1 mechanism. Primary
alcohols react by the SN2 mechanism.
141‫تركيب ص‬
4- Reaction of alcohols with phosphorus halides:
Phosphorus halides react with primary or secondary alcohols to produce good
yields of primary and secondary alkyl halides. The two phosphorus halides used
are PBr3 (phosphorus tribromide) and the phosphorus iodine combination.
142‫تركيب ص‬
5- Reaction of alcohols with thionyl chloride:
Thionyl chloride, as studied before, is often the best reagent for converting an
alcohol to an alkyl chloride (Refer to alkyl halides).
143‫تركيب ص‬
6- Dehydration reaction of alcohols:
a- Formation of alkenes:
b- The Pinacol rearrangement:
144‫تركيب ص‬
The pinacol rearrangement is formally dehydration. The reaction is acid
catalyzed, and the first step is protonation of one of the hydroxyl oxygens. Loss
of water gives a tertiary carbocation, as expected for any tertiary alcohol.
144‫تركيب ص‬
Migration of a methyl group forms a resonance-stabilized carbocation that
is even more stable than a tertiary carbocation.
144‫تركيب ص‬
The second resonance structure is particularly stable because all the atoms
have octets of electrons. This extra stability is the deriving force for the
rearrangement. Deprotonation of the resonance-stabilized cation gives the
product, pinacolone.
145‫تركيب ص‬
7- Esterification of alcohols:
a) Carboxylic esters:
Replacement of the ¬OH group of a carboxylic acid with the ¬OR group of an
alcohol gives a carboxylic ester. The following reaction is called Fischer
esterification.
145‫تركيب ص‬
The order of reactivity of alcohols in Fischer esterification is: CH3OH > 1o
> 2o > 3 o .
There is a more powerful way to form an ester, an alcohol reacts with an
acid chloride in an exothermic reaction to give an ester.
146‫تركيب ص‬
b) Inorganic esters:
Many inorganic acids can form esters when reached with alcohols. The following
are examples.
146‫تركيب ص‬
Sulfonate esters have the general formula RSO2OR, e.g.
146‫تركيب ص‬
8- Reaction of alkoxides:
The alkoxide ion is a strong nucleophile as well as a powerful base. Unlike the
alcohol itself, the alkoxide ion reacts with primary alkyl halides and tosylates to
form ethers. This general reaction is called the Williamson ether synthesis. The
Williamson ether synthesis is an SN2 displacement, and the alkyl halide (or
tosylate) must be primary so that a back-side attack is not hindered. When the
alkyl halide is not primary, elimination usually results.
147‫تركيب ص‬
Examples:
𝐶𝐻3 𝐶𝐻2 − 𝑂 − 𝑁𝑎+ +
Sodium ethoxide
𝐶𝐻3 𝐼
⟶ 𝐶𝐻3 𝐶𝐻2 − 𝑂 − 𝐶𝐻3 + 𝑁𝑎𝐼
Methyl iodide
Ethyl methyl ether
B- Thiols
They are sulphur analogous of alcohols, with an ¬SH group in place of the
¬OH group. Sulphur is just below oxygen in the periodic names, using the suffix
–thiol. Common names are derived from the name of the alkyl group with the
word mercaptane. The ¬SH groups itself is called a mercapto group.
CH3-SH
CH3CH=CHCH2
CH3CH2CH2CH
-SH
IUPAC name:
Methanethiol
But-2-ene-1-thiol
Common name:
Methyl mercaptane
2-SH
Butane-1-thiol
n-butyl mercaptane
The most characteristic property of the thiols is their odour. The human
nose is very sensitive to these compounds and can detect their presence at levels
of about 0.02 parts thiol in one billion parts of air. The odour of thiol is weakened
as the number of carbon increases.
The S-H bond is less polar than the O-H bond and hydrogen bonding in
thiols is much weaker than that of alcohols. Thiols are far more acidic than
alcohols; therefore, a thiol can be quantitatively converted to its conjugate base
RS-; called an alkane thiolate anion, by alkali hydroxide.
𝑅𝑆 − 𝐻
+
Alkanethiol
𝑂𝐻−
strong base
strong acid
⟶
𝑅𝑆 −
alkane thiolate
+
𝐻𝑂𝐻
weaker acid
strong base
Methods of preparation
Thiols can be prepared by SN2 reactions of sodium hydrosulphide with
unhindered alkyl halides. The thiol product is still nucleophile, so a large excess
of hydrosulphide is used to prevent the products from undergoing a second
alkylation to give a sulphide RSR.
149‫تركيب ص‬
Reactions of thiols
Oxidation:
Oxidation of alcohols gives compounds having carbonyl groups, while
oxidation of thiols to give compounds with the C=S functions do not occur. Only
sulphur is oxidized not carbon, and gives compounds containing sulphur in
various oxidation states as possible. The sulphonic acids are the most important.
149‫تركيب ص‬
When thiol is treated with a mild oxidizing agent [I2 or K3Fe(CN)6), it
undergoes coupling to form a dimer called disulphide. The reverse reaction,
conversion of the disulphide to the thiol takes place under reducing conditions.
This disulphide link is an important structural feature of common proteins. The
disulphide bond helps hold protein chains together in the proper shapes. The
locations of the disulphide bonds determine, for example whether hair (a protein)
is curly or straight.
150‫تركيب ص‬
A sulphide can be oxidized to a sulfoxide or a sulfone, depending upon the
reaction conditions.
Chapter 4
Ethers and Epoxides
They are compounds of formula R-O-R’, where R and R’ may be alkyl
groups or aryl groups. The two alkyl groups are the same in a symmetrical ether
and different in an unsymmetrical ether.
151‫تركيب ص‬
Nomenclature of ethers
Common names:
Common names of ethers are formed by naming the two alkyl groups on
oxygen and adding the word ether.
IUPAC names:
IUPAC names use the more complex alkyl group as the root name, and the
rest of the ether is an alkoxy group.
152‫تراكيب ص‬
Nomenclature of cyclic ethers
Epoxides (Oxiranes): are three-membered cyclic ethers. The common
names of an epoxide is formed by adding “oxide” to the alkene name.
153‫تركيب ص‬
One systematic method for naming epoxides is to name the rest of the
molecule and use the term “epoxy” as a substituent, giving the numbers of the
two carbon atoms bonded to the epoxide oxygen.
153‫تركيب ص‬
Another systematic method names epoxides as derivatives of the parent
ethylene oxide. In this system the ring atoms of a heterocyclic compound are
numbered starting with the heteroatom and going in the direction to give the
lowest substituent numbers.
154‫تركيب ص‬
Oxetanes, the lest common cyclic ethers are the four-membered oxetanes.
Because these four membered rings are strained, they are more reactive than
larger cyclic ethers and open-chain ethers. They are not as reactive as the highly
strained oxiranes (epoxides) however,
154‫تركيب ص‬
Dioxanes, heterocyclic ethers with two oxygen atoms in a six-membered
ring are called dioxanes. The most common form of dioxane is the one with the
two oxygen atoms in a 1,4-relationship. 1,4-Dioxane is miscible with water, and
is widely used as a polar solvent for organic reactions.
155‫تركيب ص‬
Synthesis of ethers
1- The Williamson ether synthesis:
This method involves the SN2 attack of an alkoxide ion on an unhindered primary
alkyl halide or tosylate.
155‫تركيب ص‬
2- By alkoxymercuration-demercuration:
The alkoxymercurartion-demercuration process adds a molecule of an alcohol
across the double bond of the alkene with the formation of an ether
156‫تركيب ص‬
3- By bimolecular dehydration of alcohols:
156‫تركيب ص‬
Reactions of ethers
Autooxidation of ethers:
When ethers are stored in the presence of atmospheric oxygen, they slowly
oxidize to produce hydroperoxides and dialkyl peroxides, both of which are
explosive. Such spontaneous oxidation by atmospheric oxygen is called an
autooxidation.
157‫تركيب ص‬
Unlike alcohols, ethers are not commonly used as synthetic intermediates,
because they do not undergo many reactions. This un-reactivity makes ethers so
attractive as solvents. Even so, ethers do undergo a limited number of
characteristic reactions.
Cleavage of ethers by HBr and HI:
Ethers are cleaved by heating with HBr or HI to give alkyl bromides or
alkyl iodides. Ethers are unreactive toward bases, but they can react under acidic
conditions. Protonated ether can undergo substitution or elimination with the
repulsion of an alcohol. Ethers react with concentrated HBr or HI because these
reagents are sufficiently acidic to protonate the ether, while bromide and iodide
ions are good nucleophiles for the substitution. This reaction converts dialkyl
ethers.
The hydrohalic acids in order of their reactivity toward the cleavage of
ethers: HI > HBr > HCl.
158‫تركيب ص‬
Synthesis of epoxides
1- Base-promoted cyclization of halohydrins:
The reaction of cyclopentene with chlorine water gives the chlorohydrin.
Treatment of the chlorohydrin with aqueous sodium hydroxide gives the
epoxides.
159‫تركيب ص‬
2- Displacement of the chlorohydrin:
159‫تركيب ص‬
3- Peroxy acid epoxidation:
160‫تركيب ص‬
Chemical reaction of epoxides
1- Acid-catalyzed ring opening of epoxides:
Epoxides are much more reactive than common dialkyl ethers, because of the
large strain energy associated with three-membered ring. Unlike other ethers,
epoxides react under both acidic and basic conditions.
In water:
Acid-catalyzed hydrolysis of epoxides gives glycols with antistereochemistry. The mechanism of this hydrolysis involves protonation of
oxygen (forming a good leaving group), then a nucleophilic attack by water. Antistereochemistry results from the back-side attack of water on the protonated
epoxides.
161‫تركيب ص‬
In alcohols:
When the acid-catalyzed opening of an epoxide takes place with an alcohol
as the solvent, a molecule of alcohol acts as the nucleophile. This reaction
produces an alkoxy alcohol with anti-stereochemistry.
162‫تركيب ص‬
Using hydrohalic acids:
When an epoxide reacts with a hydrohalic acid (HCl, HBr, or HI), a halide
ion attacks the protonated epoxide.
163‫تركيب ص‬
2- Base-catalyzed ring opening of epoxides:
The reaction of an epoxide with hydroxide ion leads to the same product as the
acid-catalyzed opening of the epoxide, with anti-stereochemistry. Like
hydroxide, alkoxide ions react with epoxides to form ring-opened compounds.
163‫تركيب ص‬
Chapter 5
Phenols
Phenols differs from alcohols in having the ¬OH group attached directly to
an aromatic ring. They are named as derivatives of the simplest member of the
family, Phenol. Methylphenols have a special name “cresols”. Sometimes
phenols are named as hydroxy derivatives.
164‫تراكيب ص‬
Phenols and alcohols have some resemblance but their properties and
preparation differ to a great extent. Phenols are fairly acidic whereas alcohols are
more weakly acidic than water. They from salts with alkalis which are converted
back to the original phenol by acid.
165‫تركيب ص‬
Their acidity is weaker than carboxylic acid and even weaker than carbonic
acid and hence they are insoluble in aqueous bicarbonate solutions. Phenoxides
liberate the original phenol on treatment with carbonic acid.
𝐴𝑟𝑂𝑁𝑎 + 𝐻2 𝐶𝑂3 ⟶ 𝐴𝑟𝑂𝐻 + 𝑁𝑎𝐻𝐶𝑂3
Phenols as well as cresols are obtained from coal tar but 90% of it is
synthesized either from sodium benzene-sulphonate or by the DOW process.
165‫تركيب ص‬
DOW process:
166‫تركيب ص‬
Another industrial process for the preparation of phenol is by air oxidation
of cumene.
166‫تركيب ص‬
Preparation of phenols
1- Hydrolysis of diazonium salts:
166‫تركيب ص‬
Diazonium salts react with water to give phenols. This reaction is slow in icecold solution of diazonium salts but very rapid at elevated temperatures.
To prevent coupling of the diazonium salt with the phenol formed, the
acidity of the solution is increased and the diazonium salt is added slowly to a
large volume of boiling dilute sulphuric acid.
2- Hydrolysis of chlorobenzene:
The presence of electron withdrawing groups ortho and para to the halogen as
e.g. 2,4-dinitrochlorobenzene and 2,4,6-trinitrochlorobenzene facilitate the
hydrolysis and replacement of the halogen with OH group to give 2,4dinitrophenol and 2,4,6-trinitrophenol respectively.
167‫تركيب ص‬
3- Fusion of sulphonates with alkali:
Naphthols can be prepared from the corresponding sulphonic acids by fusion with
alkali.
168‫تركيب ص‬
Naphthols can also be made by direct hydrolysis of naphthylamines under
acid conditions. This reaction does not work in benzene series.
168‫تركيب ص‬
Reactions of phenols
1- Acidity
168‫تركيب ص‬
2- Ether formation, Williamson synthesis:
Phenols are converted into ethers by reaction in alkaline solution with alkyl
halides.
𝑂𝐻 −
𝐴𝑟𝑂𝐻 →
𝑅𝑋
𝐴𝑟𝑂− → 𝐴𝑟𝑂𝑅 + 𝑋 −
𝑎𝑞. 𝑁𝑎𝑂𝐻
𝐶6 𝐻5 𝑂𝐻 + 𝐶2 𝐻5 𝐼 →
𝐶6 𝐻5 𝑂𝐶2 𝐻5
(Phenetol)
In alkaline solutions phenol exists as the phenoxide ion which acts as
nucleophilic reagent and attacks the halide displacing the halide ion.
Methyl ethers can be prepared by reaction of methyl sulphate with
phenoxide ion.
𝐴𝑟𝑂− + (𝐶𝐻3 )2 𝑆𝑂4 ⟶ 𝐴𝑟𝑂𝐶𝐻3 + 𝐶𝐻3 𝑂𝑆𝑂3−
Usually active aryl halides react with sodium alkoxides to give the
corresponding ether.
169‫تركيب ص‬
Alkoxy groups are less activating than OH group because ethers cannot
ionize to form the extremely reactive phenoixde ion. Thus an aromatic ether is
less sensitive to oxidation than phenol.
170‫تركيب ص‬
3- Ester formation:
Phenols are usually converted into their esters by the actions of acids, acid
chlorides or anhydrides.
171 ،170‫تركيب ص‬
When esters of phenol are treated with AlCl3, the aryl group migrates from
the phenolic oxygen to an ortho or para position of the ring to give a ketone. This
reaction is called “Fries rearrangement” and is often used instead of direct
acylation for the synthesis of phenolic ketones.
171‫تركيب ص‬
4- Ring substitution:
The phenolic and phenoxide group powerfully activate aromatic groups towards
electrophilic substitution.
Phenols, like amines, are readily susceptible for oxidation and polysubstitution.
a) Halogenation
Monohalogenation is carried out in a solvent of low polarity.
172‫تركيب ص‬
On the other hand, poly-halogenated phenol is carried out by using bromine water
mixture as follows:
172‫تركيب ص‬
b) Nitration
Nitration of phenol with HNO3 gives 2,4,6-trinitrophenol (picric acid) whereas
dilute HNO3 at low temperature gives poor yields of the mononitrophenols.
173‫تركيب ص‬
p-nitrophenol is separated from the o-isomer by steam distillation. It comes
out with steam due to hydrogen bonding between the nitro group and water
molecules whereas o-nitro phenol does not form hydrogen bonding with water
but the nitro group is intramolecularly hydrogen bonded with the OH of the
phenol which is known as “Chelation”.
174‫تركيب ص‬
c) Nitrosation:
Because of the high reactivity of phenol, it can be attacked by the weak
electrophilic nitrosonium ion, NO+.
174‫تركيب ص‬
d) Sulphonation:
The product of sulphonation of phenol depends on the temperature of the reaction.
175‫تركيب ص‬
e) Alkylation and acylation:
175‫تركيب ص‬
Acylation can be affected by the acid directly in presence of ZnCl2 as a catalyst.
176‫تركيب ص‬
The acylderivative can be made by Fries rearrangement.
176‫تركيب ص‬
f) Coupling with diazonium salts (see diazonium salts).
g) Carbonation, (Kolbe reaction):
Treatment of the salt of phenol with CO2 brings about substitution of the carboxyl
group, ¬COOH, for hydrogen of the ring.
177‫تركيب ص‬
h) Reamer-Tiemann reaction:
Treatment of phenol with chloroform in aqueous NaOH introduces an aldehyde
group, ¬CHO, into the aromatic ring, generally ortho to the ¬OH.
178‫تركيب ص‬
i) Reaction wit formaldehyde:
Phenol reacts with formaldehyde in presence of acid or alkali to give
phenolformaldehyde resin (Bakelite).
178‫تركيب ص‬
Chapter 6
Aldehydes and Ketones
These are compounds containing the carbonyl group, C=O. Because the
carbonyl group is the central structural feature of aldehydes, ketones, carboxylic
acids and their functional derivatives, it is the most important functional group in
the organic chemistry.
179‫تركيب ص‬
In aldehydes, the carbonyl group is bonded to a carbon atom and a
hydrogen atom, while in ketones it is bonded to two carbon atoms. When the C=O
group is directly attached to an aromatic ring, then we are dealing with aromatic
aldehydes or ketones (either diaryl ketones or aralkyl ketones) as shown in the
above general examples.
Nomenclature
A) Aldehydes
180‫تركيب ص‬
The IUPAC system for naming aliphatic aldehydes follows the familiarly
pattern of selecting the longest carbon chain containing the carbonyl group, as the
parent alkane and then the final e is replaced by al (which is the class suffix of
aldehydes). Because the aldehyde group must be at the end of the carbon chain,
there is no need to indicate its position as numbering must start with it, i.e. CHO
is usually assumed to occupy the 1-position. In the following examples the
common names are also given in parentheses. For unsaturated aldehydes, the
presence of a carbon-carbon double or triple bond is indicated by the infix-en- or
–yn- followed by the class suffix-al.
181‫تركيب ص‬
For cyclic molecules in which the ¬CHO group is attached directly to the
ring, the molecule is named by adding the suffix – carbaldehyde to the name of
the ring. The atom of the ring to which the aldehyde group is attached is numbered
1 unless the ring (as for example a bicyclic ring) has some other fixed numbering
pattern. In such case the ¬CHO group is given a number as low suffixed as
carbaldehyde.
The common names of aldehydes (given in parentheses in the above and
the following examples) are derived from the common names of the
corresponding acids that they give on oxidation, by replacing the suffix –ic (or –
oic) by aldehyde. For example, the name formaldehyde is derived from the formic
acid, acetaldehyde from the acetic acid.
B) Ketones
In the IUPAC system, ketones are named by selecting as the parent alkane the
longest chain that contains the carbonyl group and then indicating the presence
of the carbonyl group by replacing the final e of the corresponding alkane with –
one. Numbering of the parent chain must give the carbonyl group the least
possible number.
182‫تركيب ص‬
Common names for ketones are obtained by naming the two groups
attached to the carbonyl group and adding the word ketones as a separate word
(as given in parentheses above and below). Some ketones have special trivial
names that are retained by the IUPAC system.
General methods of preparation
1) Oxidation methods:
a- Oxidation of primary and secondary alcohols:
Primary alcohols can be oxidized to aldehydes, which are further oxidized to
acids. To stop the oxidation at the aldehyde stage and prevent the formation of
acids, pyridimium chlorochromate (PCC) must be used. It is the most commonly
used reagent for oxidation of primary alcohols to aldehydes. Under these
conditions, carbon-carbon double bonds are normally not attacked.
183‫تركيب ص‬
Secondary alcohols can be oxidized to ketones, which resist further
oxidation and hence various oxidizing agents can be used to oxidize secondary
alcohols to ketones, e.g. chromic acid H2CrO4 (K2CrO4 / H2SO4 or CrO3 / H),
KMnO4 / H+.
183‫تركيب ص‬
The product may be two ketones, two aldehydes, or one aldehyde and one
ketone depending on the substitution pattern of the glycol.
b- Oxidation of 1,2-glycols by periodic acid or lead tetraacetate:
The product may be two ketones, two aldehydes, or one aldehyde and one ketone
depending on the substitution pattern of the glycol.
184‫تركيب ص‬
c- Oxidation of alkenes:
The oxidative cleavage of carbon-carbon double bond can be achieved either
through ozonolysis (refer to reactions of alkenes) or through first oxidation of the
alkene to a glycol using KMnO4 / OH¬, OsO4 (syn-hydroxylation) or RCO3H / H+
(anti-hydroxylation). The obtained glycol is then oxidized using either periodic
(HIO4) or lead tetracetate.
184‫تركيب ص‬
2) Reduction methods:
a- Rosenmund reduction:
This consists in catalytic reduction of acid chlorides using Palladium catalyst in
the presence of BaSO4 as catalyst poison.
185‫تركيب ص‬
b- Partial reduction of carboxylic acid derivatives with metal
hydrides:
Acid chlorides, acid amides, esters and nitriles can be partially reduced to
aldehydes (and not completely to alcohols) by using Lithium alkoxyaluminium
hydrides at low temperature as lithium tri-tert-butoxyaluminum hydride (LTBA)
LiAlH[OC(CH3)3]3
diisobutylaluminum
hydride
(DIBAL-H)
AlH[CH2CH(CH3)2]2 or lithium triethoxyaluminum hydride LiAlH(OEt)3.
185‫تركيب ص‬
All these reagents are milder reducing agents than lithium aluminium
hydride (LAH) LiAlH4.
3) Acid catalyzed hydration of alkyne:
186‫تركيب ص‬
Alkynes can be converted to ketones (only acetylene gives acetaldehyde)
by hydration in acid medium.
Structure of the carbonyl group
186‫تركيب ص‬
Since the oxygen atom is more electronegative than carbon, the resonance
structure II will make a large contribution to the hydride more than structure I.
Actually, the carbonyl group is a permanent dipole i.e. the carbonyl group is a
polar group with the carbon bearing a substantial partial positive charge and the
oxygen a substantial partial negative charge.
Physical properties
Because of the polarity of the carbonyl group, aldehydes and ketones are
polar compounds (simple carbonyl compounds as acetaldehyde and acetone have
a moment between 2-3 d), which interact in the pure state by dipole-dipole
interaction. This is responsible for their higher boiling points than the non-polar
compounds of comparable molecular weights (as hydrocarbons or ethers).
However, since aldehydes and ketones are lacking association by hydrogen
bonding, they have lower boiling points than the corresponding alcohols.
Chemical reactions
One of the most common reactions of aldehydes and ketones is
nucleophilic addition across their polar carbonyl group. It is self-understanding
that a nucleophile especially attacks the carbonyl catalysis of this addition as
shown in the following general equations.
188‫تركيب ص‬
As shown in mechanism 2, protonation of the carbonyl group (or a reaction
with a Lewis acid) produces a resonance-stabilized cation. Thus, the positive
charge on the carbonyl carbon is greatly increased, i.e. its eletrophilicity is
increased. Therefore, even weak nucleophiles can undergo the nucleophilic
addition on aldehydes and ketones in acidic medium.
It is clear that aldehydes are usually more reactive towards nucleophiles
than ketones (ketones are generally less electrophilic and more subjected to steric
factors than aldehydes).
189‫تركيب ص‬
Aromatic aldehydes and ketones tend to be less reactive than aliphatic ones
because of the +R effect (electron donating of the aryl (e.g. phenyl) group, which
decreases the positivity of the carbonyl carbon. Steric factors may play an
additional role in this respect.
I-
Addition of carbon nucleophiles:
This includes the addition of the following types of carbon nucleophiles:
189‫تركيب ص‬
Addition of a carbon nucleophile to the carbonyl group is one of the most
important reactions for formation of new carbon-carbon bonds.
1) Addition of hydrogen cyanides: (Cyanohydrin reaction)
Hydrogen cyanide, HCN (obtained from KCN and dil. H2SO4), adds to the
carbonyl group of aldehydes or unhindered ketones to form tetrahedral addition
products called Cyanohydrins. The characteristic structural feature of a
cyanohydrin is an ¬OH group and a ¬CN group bonded to the same carbon. For
example, HCN adds to acetaldehyde to form acetaldehyde cyanohydrin in 75%
yield. Addition of hydrogen cyanide is catalyzed by cyanide ion.
190‫تركيب ص‬
From the stereochemical point of view, as the cyanide ion can normally
approach the carbonyl carbon from either side of the molecular plane with equal
probability, two different stereoisomers may be produced.
190‫تركيب ص‬
The formed cyanohydrins can be further hydrolysed to give αhydroxyacids, e.g. acetaldehyde cyanohydrin gives dl-acetic acid.
2) Addition of salts of terminal alkynes:
The anion of a terminal alkyne (acetylide ion) is a nucleophile and adds to the
carbonyl group of an aldehyde or ketone to form a tetrahedral carbonyl addition
product. These addition compounds contain both a hydroxyl group and a carboncarbon triple bond, each of which can be further modified.
191‫تركيب ص‬
3) Addition of ylides: (The Wittig reaction)
An ylide is a carbanionoid compound in which the negatively charged carbon is
stabilized by an adjacent positively charged heteroatom, e.g. P (Phosphorus
ylides). The ylides are neutral resonance hybrid with a significant degree of
charge separation.
Aldehydes and ketones with phosphorus ylides to give alkenes and
triphenylphosphine oxide. This valuable method for preparation of alkenes is
known as the Wittig reaction.
192‫تركيب ص‬
The Wittig reaction is effective with a wide variety of aldehydes and
ketones and with ylides derived from a wide variety of methyl, primary,
secondary and allylic halides as shown in the following examples.
N.B.:
Phosphorus
ylides
themselves
are
easily
prepared
from
triphenylphopsphine and alkyl halides according to the following two-step
reaction:
193‫تركيب ص‬
4) Addition of organometallic compounds:
Organomagnesium
compounds
(Grignard
reagents)
and
organolithium
compounds are formed by the reaction of organohalogen compounds with
magnesium turnings or lithium metal respectively in ether or tetrahydrofuran as
solvent.
𝐶𝐻3 𝐶𝐻2 𝐶𝐻2 𝐶𝐻2 𝐵𝑟 + 2𝐿𝑖 → 𝐶𝐻3 𝐶𝐻2 𝐶𝐻2 𝐶𝐻2 𝐿𝑖 + 𝐿𝑖𝐵𝑟
n-butyl bromide
n-butyl lithium
organomagnesium compounds (Grignard reagents) are one of the most
versatile for the formation of carbon-carbon bonds. They, beside to the
organolithium compounds, possess the highest partial ionic character of their
metal bonds and behaves as strong nucleophiles (very strong bases) when they
react with carbonyl compounds (or other unsaturated bonds containing
compounds).
Carbanions derived from Grignard reagents are good nucleophiles and add
to the carbonyl group of aldehydes and ketones to form magnesium alkoxides as
tetrahedral carbonyl addition products. Treating this alkoxides with a dilute acid
converts them to primary, secondary or tertiary alcohols depending on the
structure of the carbonyl compound.
Treatment of formaldehyde with a Grignard reagents followed by
hydrolysis in aqueous acid gives a primary alcohol, while the same treatment of
any other aldehyde gives a secondary alcohol. A ketone, on the other hand, gives
a tertiary alcohol when it is treated with a Grignard reagent followed by
hydrolysis. The deriving force for these reactions is the attraction of the partial
negative charge on the carbon of the organometallic compounds for the partial
positive charge of the carbonyl carbon.
II-
Addition of oxygen nucleophiles
1) Addition of water:
Addition of water (hydration) to the carbonyl group of aldehydes and ketones
forms 1,1-diols (gem-diols or hydrates). Note that gem- refers to identical groups
attached to the same carbon atom. The hydrates of most aldehydes and ketones
are
unstable
and
are
rarely
isolated.
However,
chloral
(CCl3CHO
trichloroacetaldehyde) adds water to form the stable solid chloral hydrate
[CCl3CH(OH)2]. Its stability can be attributed to -1 effect of Cl-atoms and to
intramolecular hydrogen bonding.
2) Addition of alcohols: (Acetals and Ketals formation)
The addition of one molecule of an alcohol to the carbonyl group of an aldehyde
or ketone forms a hemiacetal or hemiketal (an –hydroxyether) in a reversible
process.
Most open-chain hemiacetals and hemiketals are not sufficiently stable to
be separated. Cyclic hemiacetals and hemiketals, on the other hand, are much
more stable and play a very important role in the properties of many
carbohydrates.
These reactions are commonly catalyzed by acids.
If two molecules of alcohol are added to the carbonyl group of an aldehyde
or ketone, an acetal or ketal (an –alkoxyether) is formed. Acetals and ketals are
charachterized by the presence of two alkoxy groups attached to the same carbon
atom.
Ketal formation with simple alcohols is less favourable than that of acetals,
but 1,2-glycols readily from cyclic ketals with ketones under the effect of a trace
of acid.
Acetal formation involves an acid catalyzed reaction of the initially formed
hemiacetals with the second molecule of alcohol after elimination of water
molecule. All the steps of formation of acetals (or ketals) are reversible, and hence
the aldehydes (or ketones) can be recovered by treating with dilute acids, which
reverse all these steps.
Acetal and ketal formation is used as a protecting method for carbonyl
groups of both aldehydes and ketones as would be the case in the following
transformations:
III-
Addition of sulphur nucleophiles
1) Addition of thioalcohols: (thioacetals and thioketals formation)
𝐻+
𝑅𝐶𝐻𝑂 + 2𝑅′ 𝑆𝐻 ⇔ 𝑅𝐶𝐻(𝑆𝑅′ )2 + 𝐻2 𝑂
a thioacetal
The sulphur atom of a thiol is a far better nucleophile than the oxygen of
an alcohol (RS¬ > RO¬ nucleophilicity). Thus, thiols add to the carbonyl group of
aldehydes and ketones more rapidly than alcohols to give thioacetals and
thioketlas. These reactions are also acid catalyzed. With 1,3-propanedithiol a sixmembered cyclic thioacetals or thioketals can be obtained.
Raney nickel reduction of thioacetals and thioketals give hydrocarbons.
This represents an additional method for converting carbonyl groups of aldehydes
and ketones to ¬CH2- group.
2) Addition of sodium bisulphite:
Sodium bisulphite adds to the carbonyl group of aldehydes and some unhindered
ketones, e.g. acetone, to give a crystalline salt, the bisulphite addition product.
The bisulphite adduct regenerates the carbonyl compound when treated with
dilute acids. Hence, this reaction can be used for separation of aldehydes and
methyl ketones from other substances.
IV-
Addition of nitrogen nucleophiles
In this type of nucleophilic addition reactions, the addition product undergoes
further β-elimination of water (dehydration), i.e. the reaction ends with a
condensation product.
Z
Reagents
Product
R
RNH2
∖
𝐶 = 𝑁 − 𝑅 imine
∕
1o aliph. Amine
Ar
Ar-NH2
1o aromatic anine
∖
𝐶 = 𝑁 − 𝐴𝑟
∕
Schiffs base (anils)
HO
HONH2
Hydroxylamine
NH2
NH2-NH2
Hydrazine
∖
𝐶 = 𝑁 − 𝑂𝐻 oxime
∕
∖
𝐶 = 𝑁 − 𝑁𝐻2
∕
hydrazone
Ph-NH
Ph-NH-NH2
Phenylhydrazine
∖
𝐶 = 𝑁 − 𝑁𝐻 − 𝑃ℎ
∕
Phenylhydrazone
NH2CONH
NH2CONH-NH2
Semicarbazide
∖
𝐶 = 𝑁 − 𝑁𝐻𝐶𝑂𝑁𝐻2
∕
Semicarbazone
NH2CSNH
NH2CSNH-NH2
Thiosemicarbazide
∖
𝐶 = 𝑁 − 𝑁𝐻𝐶𝑆𝑁𝐻2
∕
Thiosemicarbazone
1) Ammonia and its derivatives:
Ammonia, primary aliphatic amines (RNH2), and primary aromatic amines
(ArNH2) react with the carbonyl group of aldehydes and ketones in the presence
of an acid catalyst to give imines (or Schiff bases). Formaldehyde, exceptionally,
forms with ammonia in a tricyclic compound called hexamethylene tetramine
(CH2)6N4 (Urotropine) which has urinary antiseptic activity.
One of the chief values of imines is that the carbon-nitrogen double bond
can be reduced by hydrogen in the presence of a nickel or other transition metal
catalyst to a carbon-nitrogen single bond. Thus a primary amine is converted to a
secondary amine.
Secondary amines react with aldehydes and ketones to form enamines. The
name enamine is derived from –en to indicate the presence of a carbon-carbon
double bond and amine to indicate the presence of an amino group.
2) Hydrazine and related compounds:
Aldehydes
and
ketones
react
with
hydrazine,
phenylhydrazine
and
hydroxylamine to form hydrazone, phenylhydrazones and oximes respectively as
illustrated in the following example.
These condensation products mostly are well crystalline solids, which can
be used for the identification of aldehydes and ketones. Hydrazones are
intermediates in the Wolf-Kishner reduction of carbonyl groups to methylene
groups. The derivatives of ammonia and hydrazine most common used for
reaction with aldehydes and ketones are shown in the previous table. The detailed
mechanism of these condensation reactions is as follows:
These condensation reactions are best carried out in moderately acid
medium (pH ~ 4) by using acetic acid catalyst. Excess acid will protonate the
amine compound itself, which then loses its nucleophilicity.
V-
Reactions at the α-carbon atom
a- Acidity of the α-hydrogens:
A carbon atom adjacent to a carbonyl group is called α-carbon, and hydrogen
atoms attached to it are called α-hydrogens. Because carbon and hydrogen have
comparable electronegativity, a C-H bond normally has a little polarity, and a
hydrogen atom bonded to carbons shows low acidity. The situation is different,
however, for hydrogens α to a carbonyl group; α-hydrogens are more acidic than
acetylenic hydrogens.
Type of bond
pKa
CH3CH2O-H
16
CH3COCH2-H
20
𝐶𝐻3 𝐶 ≡ 𝐻
25
CH2=CH-H
36
CH3CH2-H
45
The increased acidity of a C-H α to a carbonyl group relative to other C-H
bonds makes these hydrogens to be removable as a proton by a strong base. This
can be mainly attributed to the fact that resulting enolate anion is a resonancestabilized hybrid of two major contributing structures.
When such resonance-stabilized anion reacts with a proton donor, it may
do so either on oxygen or on the α-carbon. Protonation on oxygen gives an enol
(en- to show that it is alkene plus-ol to show that it is an alcohol). Keto and enol
forms are constitutional isomers.
b- Keto-enol tautomerism:
Under ordinary conditions, all aldehydes and ketones having at least one αhydrogen are in equilibrium with the corresponding enol forms. Interconversion
of these isomers is catalyzed by acids and bases. In acid, protonation of the
carbonyl group occurs first, while in base, abstraction of the α-hydrogen atom is
the initial step. This keto-enol interconversion is the most common form of
tautomerism. For most simple aldehydes and ketones, the position of the
equilibrium in keto-enol tautomerism lies far on the side of the keto form because
a carbon-oxygen double bond is stronger than a carbon-carbon double bond. For
acetaldehyde and acetone, the keto form predominates by better than 90% at
equilibrium.
For certain types of molecules, the enol form may be the major form and
in some cases the only from present at equilibrium. In 1,3-cyclohexanedione and
2,4-pentanedione and other β-diketones, where an α-carbon is substituted with
two carbonyl groups, the position of equilibrium shifts in favour of the enol form.
The enols are stabilized by conjugation of the pi system of the carboncarbon double bond and the carbonyl group. The enol of 2,4-pentanedione is
further stabilized by intramolecular hydrogen bonding.
c- Racemization
When enantiometrically pure (either the R or the S) 3-phenyl-2-butanone is
dissolved in ethanol, no change occurs in the optical activity of the solution over
time. If, however, a trace of either acid (for example, aqueous HCl) or a base (for
example sodium ethoxide) is added, the optical activity of the solution begins to
decrease and gradually drops to zero. When 3-phenyl-2-butanone is isolated from
this solution, it is found to be a racemic mixture. Furthermore, the rate of
racemiation is proportional to the concentration of acid or base. These
observations can be explained by a rate determining acid- or base-catalyzed
formation of achiral enol intermediate. Tautomerism of the achiral enol to the
chiral keto form generates the R and S enantiomers with equal probability.
Racemization by this mechanism occurs only at α-carbon stereocenters with at
least one α-hydrogen.
d- Halogenation:
Aldehydes and ketones react at an α-carbon atom with bromine and chlorine to
form α-haloaldehydes and α-haloketones. This α-halogenation is catalyzed by
acid or base.
In base catalyzed halogenation, the slow step is the formation of an enolate
anion followed by reaction with halogen by nucleophilic attack.
A major difference exists between acid catalyzed and base-catalyzed
halogenation. In principle, both can lead to polyhalogenation. In practice the rate
of acid-catalyzed introduction of a second halogen is considerably less than the
rate of first halogenation because introduction of an electronegative α-halogen
atom destabilizes the enol. Thus, it is generally possible to stop acid-catalyzed
halogenation at the monohalogenated product. In base-catalyzed halogenation, on
the other hand, the rate of second halogenation is more rapid than the first. This
is because introduction of an electronegative halogen atom on an α-carbon further
increase the acidity of remaining α-hydrogens, and thus each successive αhydrogen is removed more rapidly than the previous one. For this reason, base
catalyzed halogenation is generally not a useful synthetic route for
monohalogenation
of
carbonyl
compounds.
However,
base
catalyzed
halogenation is useful in the oxidation of methyl ketones by the haloform
reaction.
e- The aldol condensation:
The aldol condensation is the result of the addition of enolate anions to aldehydes
and ketones.
The product obtained from the reaction of acetaldehyde in base is the dimer
3-hydroxubutanal, which has been commonly named as aldol (it is both an
aldehyde ald- and an alcohol –ol). All the reactions of this type are thus known
as aldol addition (aldol condensation or simply aldol reaction). The characteristic
structural feature of the product of an aldol reaction is the presence in it of a
hydroxyl group β to the carbonyl group.
The key step for base-catalyzed aldol reactions is nucleophilic addition of
anion from one carbonyl-containing molecule to the carbonyl of another as
illustrated by the above example of the aldol reaction of acetaldehyde.
β-hydroxyaldehydes and β-hydroxyketones are very easily dehydrated, and
often the conditions necessary to bring about an aldol reaction are sufficient to
cause dehydration. The major product from dehydration of an aldol reaction
product is one which the carbon-carbon double bond is conjugated with the
carbonyl group, that is, product is an α,β-unsaturated carbonyl compound.
Conjugation of unsaturation imparts added stability to molecules compared with
unconjugated unsaturation.
The ingredients in the key step of an aldol reaction are an enolate anion
and an enolate anion acceptor. In self-reactions, both roles are played by one kind
of molecule. Mixed aldol reactions (crossed aldol reaction) are also possible, as
for example the mixed aldol reaction between acetone and formaldehyde.
Formaldehyde cannot provide an anion because it has no α-hydrogen, but it can
function as a particularly good anion acceptor because its carbonyl group is
unhindered. Acetone forms an anion, but its carbonyl group, bonded to two alkyl
groups, is a poorer anion acceptor than that of formaldehyde. Consequently, the
mixed aldol reaction between acetone and formaldehyde gives 4-hydroxy-2butanone.
The Claisen condensation, Knovenagel and Perkin reactions as well as the
benzoin condensation are another reaction which also involve addition of
carbanions on the carbonyl group of benzaldehyde (will be discussed later).
Finally, intramolecular aldol reactions of diketones are often used for
making five- and six-membered rings.
Planning synthesis using aldol condensations:
It is now clear that the aldol condensations can be used to produce two
types of products: (1) β-hydroxy aldehydes and ketones (aldols) and (2) α,βunsaturated aldehydes and ketones. If a target molecule has one of these
functionalities, an aldol reaction should be considered. To determine the starting
components of such reaction, divide the structure at the α,β-bond to the double
bond.
VI-
Oxidation of aldehydes and ketones
1- Oxidation to acids:
Aldehydes, aliphatic or aromatic, are easily oxidized to the corresponding acids
by strong oxidizing agents as KMnO4 / H+, K2Cr2O7 / H+ or even when exposed
to air. The process is a two-electron oxidation as shown by the following balanced
half-reaction.
Milder oxidizing agents as Tollen’s reagent and Fehling’s solution can also
oxidize aliphatic aldehydes to acids. The later reagent does not reduce aromatic
aldehydes, but the former does. Neither of them, however, can reduce any ketone.
Ketones, in contrast to aldehydes, are less readily oxidized to acids because
breaking of C-C bonds is involved. Strong oxidizing agents, as HNO3, K2Cr2O7..,
however may attack the α-carbon of ketones as in the following equations.
2- Oxidation to haloform and acids:
𝐶𝐻3 𝐶𝑂𝐶𝐻3 + 𝐼2 + 𝑁𝑎𝑂𝐻 → 𝐶𝐻3 𝐶𝑂𝐶𝑙3
Triiodoacetone
𝑁𝑎𝑂𝐻
→
𝐶𝐻3 𝐶𝑂𝑂𝑁𝑎 +
Sodium acetate
𝐶𝐻𝐼3
iodoform
Ketones containing the CH3CO moiety (whether aliphatic or aromatic) are
readily oxidized by sodium hypohalite, NaOX, (Halogen / NaOH) to haloform
and the sodium salt of the corresponding acid. Thus acetone and acetophenone
give with iodine and sodium hydroxide iodoform and sodium acetate or sodium
benzoate respectively (The haloform reaction is also given by compounds
containing –CH(OH)CH3 group).
VII- Reduction of aldehydes and ketones
Aldehydes are reduced to primary alcohols and ketones to secondary alcohols. In
addition, both aldehyde and ketone carbonyl groups can be reduced to ¬CH 2group.
1) Reduction to alcohols:
The carbonyl group of an aldehyde or ketone is reduced to an alcohol group under
various reduction conditions, e.g. using metal / acid or Na / alcohol, however the
following are the most commonly used.
Catalytically: using hydrogen in the presence of a transition metal catalyst,
most commonly finely divided palladium, platinum or nickel.
Metal hydride reduction: it is by far the most common laboratory method
for reduction of the carbonyl group by using sodium borohydride (NaBH4),
lithium aluminium hydride (LiAlH4) or their derivatives. These compounds
behave as sources of hydride ion, a very strong nucleophile.
Lithium aluminium hydride (LAH) is a very powerful reducing agent; it
reduces not only the carbonyl group of aldehydes and ketones rapidly but also
those of carboxylic acids. Both LAH and sodium borohydride are selective in that
neither reduces isolated carbon-carbon double bond. For molecules in which the
carbon-carbon double bond is conjugated with the carbonyl group, however, it is
sometimes observed that both functional groups are reduced. Reduction of both
functional groups is more common with LiAlH4 than with NaBH4.
2) Reduction of a –C=O group to a ¬CH2 group:
Several methods are available for converting the carbonyl group of an aldehyde
or ketone to a methylene (-CH2-) group. These are:
a- Clemmenson reduction: (acidic pH)
This involves refluxing the aldehyde or ketone with amalgamated zinc (zinc with
a surface layer of mercury) in concentrated HCl.
Because the Clemmenson reduction requires the use of conc. HCl, it cannot
be used to reduce a carbonyl group in molecule that also contains acid-sensitive
groups, as for example a tertiary alcohol that might undergo dehydration or an
acetal that is hydrolysed and resulting carbonyl group is also reduced. The
mechanism of Clemmenson reduction is not well understood.
b- Wolf-Kishner reduction: (alkaline pH)
In this reduction, the aldehyde or ketone is treated with hydrazine to form a
hydrazone, which is then heated with concentrated sodium hydroxide in a highboiling solvent as diethylene glycol.
3) Cannizaro reaction:
Aldehydes having no α-hydrogen atoms undergo self-oxidation-reduction when
treated with conc. Alkali, whereby one molecule is oxidized to the corresponding
acid, while the other is reduced to alcohol.
Mechanism of Cannizaro reaction:
The Cannizaro mechanism begins with a nucleophilic attack by hydroxide
ion on the carbonyl group of the aldehyde that will be oxidized, the resulting
anion is a good hydride (H:¬) donor that transfers hydride to the aldehyde that
will be reduced. This is the actual oxidation-reduction step. The products are a
carboxylic acid and an alkoxide. A fast proton transfer completes the reaction.
In crossed Cannizaro reactions, where two different aldehydes with no αhydrogen atoms are treated with alkali, it is the aldehyde having the more
positively charged carbonyl carbon which is preferentially oxidized and the other
is reduced. Thus a crossed Cannizaro reaction between formaldehyde and an
aromatic aldehyde is expected to proceed through reduction of the aromatic
aldehyde and oxidation of formaldehyde, i.e. the net result of such reaction is the
formation of an aromatic alcohol and a formate anion.
Chapter 7
Carboxylic Acids & their Derivatives
(The Carboxylic Acid Family)
Carboxylic acids and its derivatives are one of the most important classes
of organic compounds. Carboxylic acids are compounds containing the carboxyl
group [-COOH]. A carboxyl group is composed of a carbonyl group [C=O]
directly attached to a hydroxyl group [OH].
∖
𝐶=𝑂
∕
𝐻𝑦𝑏𝑟𝑖𝑑𝑖𝑧𝑎𝑡𝑖𝑜𝑛 = 𝑠𝑝2
𝐵𝑜𝑛𝑑 𝑎𝑛𝑔𝑙𝑒𝑠 = 120𝑜
The carbon atom of the carboxyl group (often written as ¬COOH, CO2H)
is sp2 hybridized and consequently the three atoms attached to it are planar.
Carboxylic acid derivatives are compounds with functional groups that can
be converted to carboxylic acids by a simple acidic or basic hydrolysis. The most
important acid derivatives are esters, amides, acid halides, acid anhydrides, and
nitriles.
So, all the members of the carboxylic acid family (except nitriles) contain
a carbonyl group bonded to at least one heteroatom: oxygen, nitrogen, or a
halogen atom (in contrast to aldehydes and ketones, in which the carbonyl group
is attached to hydrogen or alkyl group respectively).
I.
Some of the common acids are:
Carboxylic Acids
Nomenclature of carboxylic acids
a) Common names:
The common names are usually based on the natural source from which the acids
were first obtained, i.e. formic acid (an acid obtained from the bite of ant Latin
Formica), acetic acid (obtained from vinegar: Latin acetum), butyric acid
(obtained from rancid butter), caproic acid (from goat, Latin caper), fatty acid
(long-chain, containing even number of C- atoms obtained from fats and oils),
and so on.
The position of substituents is indicated by Greek letters α, β, γ, δ, where
α is given to the carbon atom adjacent to the carboxyl carbon atom. The prefix
iso- is sometimes used for acids ending with ¬CH(CH3)2 grouping.
Names of some carboxylic acids
Formula
Common name
IUPAC name
Monocarboxylic acids:
HCO2H
Formic acid
Methanoic acid
CH3CO2H
Acetic acid
Ethanoic acid
CH3CH2CO2H
Propionic acid
Propanoic acid
CH3CH2CH2CO2H
Butyric acid
Butanoic acid
CH3(CH2)3CO2H
Valeric acid
Pentanoic acid
CH3(CH2)4CO2H
Caproic acid
Hexanoic acid
CH3(CH2)10CO2H
Lauric acid
Dodecanoic acid
CH3(CH2)14CO2H
Palmitic acid
Hexadecanoic acid
CH3(CH2)16CO2H
Stearic acid
Octadecanoic acid
CH3CH(OH)CO2H
Lactic acid
2-hydroxypropanoic acid
HO2C.CHOH.CHOH.CO2H Tartaric acid
2,3-dihydroxy-1,4-butanedioic acid
𝐶𝐻 − 𝐶𝑂𝑂𝐻
∥
𝐶𝐻𝐶𝑂𝑂𝐻
Cis-2-butenedioic acid
Maleic acid
Dicarboxylic acids:
𝐶𝐻 − 𝐶𝑂𝑂𝐻
∥
𝐶𝑂𝑂𝐻
𝐶𝑂𝑂𝐻
∥
𝐶𝑂𝑂𝐻
Formic acid
Trans-2-butenedioic acid
Oxalic acid
Ethanedioic acid
HOOCCH2COOH
Malonic acid
Propanedioic acid
HOOC(CH2)2COOH
Succinic acid
Butanedioic acid
HOOC(CH2)3COOH
Glutaric acid
HOOC(CH2)4COOH
Adipic acid
Hexanedioic acid
HOOC(CH2)5COOH
Pimelic acid
Heptanedioic acid
b) IUPAC names:
In the IUPAC system acids are named as alkane derivative, i.e. as alkanoic acid.
For this purpose, the longest carbon chain that contains the carboxyl group is
selected. The carbon of CO2H group is numbered as 1. All the other rules for
naming organic compounds apply. Thus, HCO2H, containing one carbon atom
only is named as methane derivative and the IUPAC name is methanoic acid.
If substituent groups are present, their position is indicated by numbers 2,
3, 4, 5 …:
Thus, lactic acid, CH3CH(OH)CO2H is named as 2-hydroxypropanoic
acid. And:
IUPCAC name: 2,3-dibromobutanoic acid
Common name: α,β-dibromobutyric acid
𝐶𝐻3 𝐶𝐻𝐶𝑂2 𝐻
|
𝑁𝐻2
is named as:
α-amino-propionic acid (Alanine: common name)
2-amino propanoic acid (IUPAC name).
Although, aliphatic dicarboxylic acid can be named as dioic acids but they
are known almost exclusively by their common names. If substituent groups are
present, their position is indicated either by Greek letters (common nomenclature)
or by numbers 2, 3, 4… beginning from the side which gives the substituents the
least possible numbers.
Unsaturated acids are named using the name of the corresponding alkene,
with the final ¬e replaced by ¬oic acid. The carbon chain is numbered, starting
with the carboxylic carbon, and a number gives the location of the double bond.
The stereochemical terms cis- and trans- (Z and E) are used as they are with other
alkenes.
In case of carboxyl group being attached to cycloalkenes, the acids are
named as cycloalkane carboxylic acid, e.g.
Physical properties of carboxylic acids
Like alcohol and water, the carboxylic acids are polar compounds and form
strong hydrogen bonds. Therefore, first few members are water soluble. As the
alkyl (R) group increases in size, they behave more like hydrocarbons and
become water insoluble.
Carboxylic acids are higher boiling than the corresponding alcohols. This
is because of the strong hydrogen bonding in acids and it has been suggested that
they are exist as dimers:
Acidity of carboxylic acids
Carboxylic acids are acidic compounds and react with alkalies like sodium
hydroxide and sodium bicarbonate to make salts.
𝑅𝐶𝑂𝑂𝐻 + 𝑁𝑎𝐻𝐶𝑂3 ⟶ 𝑅𝐶𝑂𝑂− 𝑁𝑎+ + 𝐻2 𝑂 + 𝐶𝑂2
This reaction is used as a qualitative test to distinguish between acids and
phenols. Carboxylic acids are weak acids and ionize in water to give acidic
solutions and the equilibrium constant, Ka is called the acid dissociation or
ionization constant:
Structural effects on acidity
If we compare the acidity of water, alcohols and acids, we find that the
later are much more acidic.
The reason why acids are more acidic than alcohols and water is that the
anion from the acid is much more stable than the acid itself and from the anions
of alcohol and water, because of resonance as shown above. Because anion of the
acid is more stable, therefore equilibrium shifts to the right, thus making the acids
more acidic. No such stabilization is available in the case of –OH or –OR.
Substance on the α-carbon atom of the carboxylic acids also effect the
acidity. Thus, chloroacetic acid is more acidic than acetic acid because of the
electron-withdrawing Cl atom on α-carbon. Trichloroacetic, having 3 Cl atoms at
the carbon is stronger acid than dichloro- and monochloro-acetic acid for the
same reason.
The electron-withdrawing Cl atom withdraws electrons through the αbonds (Inductive effect) thus making H atom, H+ i.e., more acidic F, Cl, Br, NO2,
CN, SO3H, CO2H are electron-withdrawing groups and acid-strengthening. The
inductive effect falls off as the chlorine atom moves away from the carboxylic
group; thus, the pKa for chlorobutyric acids are:
Acids
pKa
Relative acidity
CH3CH2CH2COOH
4.82
1
𝐶𝐻3 𝐶𝐻2 𝐶𝐻𝐶𝑂𝑂𝐻
|
𝐶𝑙
𝐶𝐻3 𝐶𝐻𝐶𝐻2 𝐶𝑂𝑂𝐻
|
𝐶𝑙
𝐶𝐻2 𝐶𝐻2 𝐶𝐻2 𝐶𝑂𝑂𝐻
|
𝐶𝑙
2.85
9.2
4.05
6
4.52
2
Electron-donating groups, on the other hand, decrease the acidity. Thus,
propionic acid butanoic acid having CH3- and CH3CH2 groups, which are
electron-donating, are weaker acid than acetic acid.
Acid
pKa
H-CO2H
3.71
CH3-CO2H
4.74
CH3-CH2-CO2H
4.85
CH3-CH2-CH2-CO2H
Synthesis of carboxylic acids
1) Oxidation of alcohols, aldehydes or ketones:
Carboxylic acids could be obtained by oxidation of alcohols, aldehydes or
ketones using acid dichromate, acid permanganate or nitric acid.
[𝑂]
[𝑂]
𝑅𝐶𝐻2 𝑂𝐻 → [𝑅𝐶𝐻𝑂] → 𝑅𝐶𝑂𝑂𝐻
𝑅∖
𝑅′𝐶𝐻2
[𝑂]
∕ 𝐶𝐻𝑂𝐻 →
𝑅∖
𝑅′𝐶𝐻2
[𝑂]
∕ 𝐶 = 𝑂 → 𝑅𝐶𝑂𝑂𝐻 + 𝑅′𝐶𝑂𝑂𝐻
Methyl ketones are oxidized by halogen in alkaline medium giving
carboxylic acids in addition to haloform.
1) 𝐻2 /𝑁𝑎𝑂𝐻 . 2) 𝐻 +
𝑅 − 𝐶𝑂 − 𝐶𝐻3 →
𝑅′ 𝐶𝑂𝑂𝐻
Methyl ketone
carboxycyclic acid
+
𝐶𝐻𝑋3
haloform
2) Hydrolysis of nitriles:
A very good synthetic method is the hydrolysis of nitriles (cyanides) with acid or
alkali.
As nitriles are usually obtained by the nucleophilic substitution of alkyl
halides by cyanide ions, this method converts an alkyl halide to a carboxylic acid
with additional carbon atoms.
3) Carboxylation of Grignard reagents:
A Grignard reagent, at below 0oc, adds to solid carbon dioxide. Acid hydrolysis
of the formed complex gives a carboxylic acid. This is another useful method of
converting an alkyl or aryl halide to a carboxylic acid with one carbon atom more.
4) Oxidation cleavage of alkenes and alkynes:
𝐾𝑀𝑛𝑂4 . ∆
𝑅 − 𝐶𝐻 = 𝐶𝐻𝑅′→
𝑅𝐶𝑂𝑂𝐻 + 𝑅′𝐶𝑂𝑂𝐻
5) Malonic ester synthesis:
Substituted acetic acids can be obtained through the malonic ester synthesis. In
this method, malonic ester (diethyl malonate) is alkylated or acylated on the
carbon that is α to both carbonyl groups and the resulting derivative is hydrolysed
and allowed to decarboxylate. Sodium ethoxide deprotonates malonic ester and
the resulting resonance stabilized enolate ion are easily alkylated by an
unhindered alkyl halide, tosylate, or other electrophilic reagent.
As specific example: when RX and R’X are CH3X and C2H5X respectively
α-methylbutyric acid is the produced distributed acetic acid.
Chemical reaction of carboxylic acids
1- Salt formation:
Carboxylic acids are acted upon by strongly electropositive metals with the
liberation of hydrogen and formation of a salt.
The salts are also formed when the acid is reacted with an alkali. Because
mineral acids are stronger than carboxylic acids, addition of a mineral acid
converts a carboxylic acid salt back to the original carboxylic acid.
Salts of carboxylic acids are named simply by naming the cation, and then
naming the carboxylate ion by replacing the –ic acid part of the acid name with –
ate. Soap is a common example of carboxylate salts, consisting of the soluble
sodium salts of long-chain fatty acids.
2 𝑅𝐶𝑂𝑂𝐻 + 2 𝑁𝑎 → 2 𝑅𝐶𝑂𝑂− 𝑁𝑎+ + 𝐻2
𝐶𝐻3 𝐶𝑂𝑂𝐻
+
Acetic acid
𝑁𝑎𝑂𝐻
→
𝐶𝐻3 𝐶𝑂𝑂− 𝑁𝑎+
sodium hydroxide
+
𝐻2 𝑂
sodium acetate
(sodium ethanoate)
𝐶𝐻3 𝐶𝐻2 𝐶𝐻2 𝐶𝐻2 𝐶𝑂𝑂𝐻
pentanoic acid
valeric acid
+
→
𝐶𝐻3 𝐶𝐻2 𝐶𝐻2 𝐶𝐻2 𝐶𝑂𝑂− 𝐿𝑖 +
lithium hydroxide
lithium pentanoate
𝐿𝑖𝑂𝐻
lithium valerate
(common name)
2- Formation of esters:
Carboxylic acids react with alcohols to form esters. The reaction is reversible, the
forward reaction being known as esterification and the backward reaction as
hydrolysis.
The direct esterification is always slow, but is catalyzed by inorganic acid,
as conc. sulphuric acid or gaseous hydrogen chloride (Fischer-Spier
esterification). Alternatively, water may be removed from the reaction mixture
by the addition of immiscible organic solvent as benzene or carbontetrachloride,
each of which forms a binary mixture with water that distils over at lower
temperature than water (Azeotropic distillation of water).
The mechanism of esterification using primary or secondary alcohols is a
typical acid-catalyzed nucleophilic substitution at the acyl carbon. The acid
catalyst protonates the carboxyl group and thus activates toward nucleophilic
attack.
Carboxylic acids are converted to their methyl esters very simply by adding
an ether solution of diazomethane. The only by-product is nitrogen gas, and
excess diazomethane also evaporates. The reaction of diazomethane with
carboxylic acids probably involves transfer of the acid proton, giving a
methyldiazonium salt. This diazonium salt is excellent methylating agent with
nitrogen gas as a leaving group.
Examples:
3- Formation of acid halides:
Phosphorus trihalides or phosphorus pentahalides (chlorides or bromides)
converted carboxylic acids into their corresponding acid halides (acyl halides).
Acid chlorides are best prepared by using thionyl chloride (SOCl 2) or oxalyl
chloride (COCl)2 because they form gaseous by products that do not contaminate
the product.
4- Formation of acid amides:
The initial reaction of carboxylic acids with ammonia or an amine give an
ammonium salt. Heating this salt to above 100 oc forms the acid amide with
elimination of water.
5- Reduction of carboxylic acids:
a- Reduction to alcohols:
Lithium aluminium hydride (LiAlH4 or LAH) reduces carboxylic acids to
primary alcohols. The aldehyde is an intermediate in this reduction, but it cannot
be isolated because it is reduced more easily than the original acid. Lithium
aluminium hydride is a strong base, and the first step is deprotonation of the acid.
Hydrogen gas is evolved with the formation of the lithium salt and aluminium
hydride (AlH3).
The latter then adds to the carboxyl group of the lithium carboxylic salt.
Elimination gives an aldehyde, which is quickly to a lithium alkoxide. The
alkoxide is attached with water to give lastly the primary alcohol.
Carboxylic acids are also reduced to primary alcohols by diborane (B 2H6),
which reacts with the carboxyl group faster than with any other carbonyl function.
Diborane often shows excellent selectivity, where a carboxylic acid is reduced
while a ketone is unaffected (LiAlH4 would also reduce the ketone to a secondary
alcohol).
b- Reduction to aldehydes:
Reduction of carboxylic acids to aldehydes is difficult because aldehydes are
more reactive than carboxylic acids towards most reducing agents. Almost any
reagent that reduces acids to aldehydes also reduces aldehydes to primary
alcohols (a derivative of the acid that is more reactive than the aldehyde is
needed). Lithium tri-tert-butoxyaluminium hydride, LiAl[OC(CH3)3]3H, is a
weaker reducing agent than lithium aluminium hydride. It reduces acid chlorides
because they are strongly activated toward nucleophilic addition of a hydride ion.
Under these conditions, the aldehydes react more slowly, and thus are easily
isolated. (This is also affected through the Rosenmund reduction).
c- Reduction to alkanes:
Prolonged heating under pressure with conc. HI and small amount of red
phosphorus, or heating with hydrogen at high temperature in the presence of
catalysts reduces carboxylic acids into paraffins.
6- Oxidation:
All acids, except formic acid, are extremely resistant to oxidation, but prolonged
heating with oxidizing agents ultimately produces carbon dioxide and water.
7- Halogenation:
Carboxylic acids react slowly with chlorine or bromine in the cold, but at high
temperatures and in the presence of small amount of red phosphorus, reaction
proceeds smoothly to give α-halogeno-acids.
This specific halogenation of the α-position of carboxylic acid is known as
Hell-Volhard-Zelinsky reaction (H.V.Z. reaction). A possible mechanism is as
follows:
8- Decarboxylation:
Sodium salts of carboxylic acids are decarboxylated to paraffins when heated
with sodalime in the dry state.
The thermal decarboxylation of free acids may be as follows:
β-ketoacids or their salts are more readily decarboxylated, when they are
heated to 100-150oc. This case of decarboxylation of β-ketoacids is due to, when
the salt decarboxylates, it forms a resonance-stabilized anion. This anion is much
more stable than the anion RCH2-, that would be produced by decarboxylation of
an ordinary carboxylic acid.
When the acid itself decarboxylates, it can do so through a six-membered
cyclic transition state, which initially gives an enol form that quickly tautomerizes
to the product.
9- Formation of amines: (Schmidt reaction)
Carboxylic acids react with hydrazoic acid (HN3) in the presence of sulphuric
acid to form primary amine under elimination of carbon dioxide. The Schmidt
reaction is a modification of the Curtius reaction (refer to amines). The
mechanism of both reactions involves an alkyl migration (1,2-shift) to an electron
deficient nitrogen.
Carboxylic acid derivatives differ mostly in the nature of the nucleophile
bonded to the acyl carbon: -OH in the acid, -OR in the ester, -X (halogen) in the
acid halides, and –NH2 (or an amine) in the amide.
II.
Carboxylic Acid Derivatives
They can be represented by the following general formula:
Nucleophilic acyl substitution is the most common method for
interconverting these derivatives. The mechanisms of these substitutions vary,
and they depend on whether the reaction takes place in acid or base. Generally,
such nucleophilic acyl substitution is represented as follows:
Nomenclature of acid derivatives
1- Esters of carboxylic acid:
Esters are carboxylic acid derivatives in which the hydroxyl group (-OH) is
replaced by an alloy group (-OR). The names of esters consist of two words that
reflect their composite structure. The first word is derived from the alkyl group
of the alcohol, and the second word from the carboxylate group of carboxylic
acid. The IUPAC name is derived from the IUPAC names of the alkyl group and
the carboxylate, while the common name is derived from the common names of
each.
*** Lactones:
Cyclic esters are called lactones. A lactone is formed from an open chain
hydroxy acid in which the hydroxyl group has reacted with the acid group to form
an ester. The IUPAC names of lactones are derived by adding the term lactone at
the end of the name of the parent acid. The common names of lactones, used more
often than IUPAC names, are formed by changing the –ic acid ending of the
hydroxy acid to olactone. Substituents are named just as they are on the parent
acid.
2- Amides:
An amide is a composite of a carboxylic acid and ammonia or an amine.
An amide of the form R-CO- NH2 is called a primary amide because there
is only one carbon atom bonded to the amide nitrogen. An amide with an alkyl
group on nitrogen (P-CO-NHR) is called a secondary amide or an N-substituted
amide. Amides with two alkyl groups on the amide nitrogen (R-CO-NR2) are
called tertiary amides or N,N-disubstituted amides. To name a primary amide,
first name the corresponding acid. Drop the –ic acid or –oic acid suffix, and add
the suffix –amide. For secondary and tertiary amides, treat the alkyl groups on
nitrogen as substituents, and specify their position by the prefix N-.
For acids that are named as alkane carboxylic acids, the amides are named
using the suffix –carboxamide. Some amides, such as acetanilide, have historical
names that are still commonly used.
*** Lactams:
Cyclic amides are called lactams, lactams are formed from amino acids,
where the amino group and the carboxyl group have joined to form an amide.
Lactams are named like lactones, and the common names of lactams are used
more often than the IUPAC names
3- Acid halides:
Acid halides, also called acyl halides. An acid halide is named by replacement
the –ic acid suffix of the acid name with –yl and the halide name. For acids that
are named as alkanecarboxylic acids, the acid chlorides are named using the
suffix-carbonyl chloride.
4- Acid anhydrides:
The word anhydride means “without water”. Anhydride nomenclature is very
simple; the word acid is changed to anhydride in both the common name and the
IUPAC name (rarely used). Anhydrides composed of two different acids are
called mixed anhydrides, and are named using the names of the individual acids.
5- Nitriles:
Nitriles contain the cyano group, -𝐶 ≡ 𝑁. Although nitriles lack the carbonyl
group of carboxylic acids, they are classified as acid derivatives because they
hydrolyze to give carboxylic acids and can be synthesized by dehydration of
amides.
Nitrile nomenclature is derived from that of carboxylic acids. The IUPAC
name is constructed from the alkane name, with the suffix –nitrile add. For
common names, the suffix –ic acid is replaced by the suffix –onitrile. For acids
that are named as alkanecarboxylic acids, the corresponding nitriles are named
using the suffix –carbonitrile. The -𝐶 ≡ 𝑁 group can also be named as a
substituent, the cyano group.
Nomenclature of multifunctional compounds
In choosing the principal group for the root name, we use the following
priorities: acid > ester > amide > nitrile > aldehyde > ketone > alcohol > amine >
alkene > alkyne.
Physical properties of carboxylic acid derivatives
Boiling points and melting points:
Esters and acid chlorides have boiling points near those of the straight
chain alkanes with similar molecular weights. These acid derivatives contain
highly polar carbonyl groups, but the polarity of the carboxyl group had only a
small effect on boiling points. Carboxylic acids are strongly hydrogen bonded in
the liquid phase, resulting in elevated boiling points. The stable hydrogen-bonded
dimer has a higher effective molecular weight and boils at a higher temperature.
Nitriles also have higher boiling points than esters and acid chlorides of similar
molecular weight. This effect results from a strong dipolar association between
adjacent cyano groups.
Amides have surprisingly high boiling points and melting points. Primary
and secondary amides participate in strong hydrogen bonding. The resonance
picture shows a partial negative charge on oxygen and a partial positive charge
on nitrogen. The positively charged nitrogen polarizes the –N-H bond, making
the hydrogen strongly electrophilic. The negatively charged oxygen’s lone pairs
are particularly effective in forming hydrogen bonds to these polarized N-H
hydrogens.
Pure tertiary amides lack –N-H bonds, so they cannot participate in
hydrogen bonding (although they are good hydrogen bond acceptors), still they
have high boiling points, close to those of carboxylic acids of similar molecular
weights. This is due to a pairing of two molecules help to stabilize the liquid
phase.
Chemical reaction of acid derivatives
1- Interconversion of acid derivatives by nucleophilic acyl substitution:
The most common reaction of acid derivative is nucleophilic acyl substitution.
Attack on the carbonyl group by a nucleophile, followed by loss of a leaving
group. Nucleophilic acyl substitutions are also called acyl transfer reactions.
Depending on the nature on of Nu:¬ and Z:¬; we can imagine converting
any acid derivative into almost any other. Reactions that actually occur generally
convert a more reactive acid derivative to a less reactive one.
a- Reactivity of acid derivatives:
Acid derivatives differ greatly in their reactivity toward nucleophilic acyl
substitution. The reactivity of acid derivatives toward nucleophilic attack depends
on their structure and on nature of the attacking nucleophile. In general, reactivity
follows this order:
Cl¬ < R-C-O¬ < RO¬ < NH2¬
This order of reactivity stems partly from the basicity of the leaving groups.
Strong bases are not good leaving groups, and the reactivity of the derivatives
decreases as the leaving group becomes more basic.
Resonance stabilization also affects the reactivity of acid derivatives. In
amides, for example, resonance stabilization is lost when a nucleophile attacks.
A smaller amount of stabilization is present in esters.
Resonance stabilization of an anhydride is like that in an ester, but the
stabilization is shared between two carbonyl groups.
Each carbonyl group receives less stabilization than an ester carbonyl.
There is little resonance stabilization of an acid chloride, and it is quite
reactive.
b- Leaving groups in nucleophilic acyl substitutions:
Reaction rate is sensitive to the nature of the leaving group. With a poor leaving
group such as alkoxide, this reaction is quite slow.
2- Acid-catalyzed nucleophilic acyl substitution:
In each substitution discussed before, a nucleophile attacks the group to form a
tetrahedral intermediate. Some nucleophiles are too weak to attack an unactivated carbonyl group. For example, an alcohol attacks the carbonyl group of
an acid chloride, but it does not attack an acid. If a strong acid protonates the
carbonyl group of the carboxylic acid, it is activated toward attack by the alcohol;
Fischer esterification is the result.
3- Hydrolysis of carboxylic acid derivatives:
All acid derivatives hydrolyze to give carboxylic acids. In most cases, hydrolysis
occurs under either acidic or basic conditions. The reactivity of acid derivatives
toward hydrolysis varies from highly reactive acyl halides to relatively nonreactive amides.
a- Hydrolysis of acid halides and anhydrides:
Acid halides and anhydrides are so reactive that they hydrolyze under neutral
conditions.
b- Hydrolysis of esters:
Acid-catalyzed hydrolysis of an ester is simply the reverse of the Fischer
esterification equilibrium. Addition of excess water drives the equilibrium toward
the acid and the alcohol. Basic hydrolysis of esters, called saponification, avoids
the equilibrium of the Fischer esterification. Hydroxide ion attacks the carbonyl
group to give a tetrahydral intermediate.
Expulsion of alkoxide ion gives the acid, and a fast proton transfer gives
the carboxylate ion and the alcohol.
The term saponification means “The making of soap”. Soap is made by the
basic hydrolysis of fats, which are esters of long chain carboxylic acids (fatty
acids) with the triol glycerol.
c- Hydrolysis of amides:
Amides undergo hydrolysis to carboxylic acids under both acidic and basic
conditions. Amides are the most stable acid derivatives, and stronger conditions
are required for their hydrolysis than for hydrolysis of an ester. Typical hydrolysis
conditions involve prolonged heating in 6 M HCl or 40 percent aqueous NaOH.
The basic and acidic hydrolysis mechanisms are similar to that for
hydrolysis of an ester.
d- Hydrolysis of nitriles:
Nitriles are hydrolysed to amides, and further to carboxylic acids, by heating with
aqueous acid or base. Mild conditions can hydrolyze a nitrile as far as the amide;
stronger conditions can hydrolyze it all the way to the carboxylic acid. Thus, the
partial hydrolysis to the amide must be carried out by careful dissolving the nitrile
in conc. H2SO4 and then pouring into cold water or by shaking the alkyl cyanide
with cold conc. HCl, heating completes the hydrolysis to the corresponding acid.
The mechanism for basic hydrolysis begins with attack by hydroxide on
the electrophilic carbon of the cyano group. Protonation gives unstable enol
tautomer of an amide. Removal of a proton from oxygen and re-protonation on
nitrogen gives the amide. Further hydrolysis of the amide to the carboxylate salt
involves the same base-catalyzed mechanism as that discussed before.
4- Reduction of acid derivatives:
Carboxylic acids and their derivatives can be reduced to alcohols, aldehydes, and
amines. Because they are relatively difficult to reduce, acid derivatives generally
require a strong reducing agent such as lithium aluminium hydride (LiAlH4).
a- Reduction to alcohols:
Lithium aluminium hydride reduces acids, acid chlorides, and esters to primary
alcohols.
b- Reduction to aldehydes:
Acid chlorides are more reactive than other acid derivatives, and they are reduced
to aldehydes by mild reducing agents such as lithium trit-butoxy) aluminium
hydride or by the Rosenmund reduction.
Esters can be reduced to aldehydes by another mild reducing agent,
diisobutylaluminum hydride (BIBAH) at very low temperature to minimize over
reduction.
c- Reduction to amines:
Lithium aluminium hydride reduces amides, azides, and nitriles to amines.
Azides, primary amides, and nitriles are reduced to primary amines. Secondary
amides are reduced to secondary amines, and tertiary amides are reduced to
tertiary amines.
5- Reactions of acid derivatives with organometallic reagents:
a- Esters and acid chlorides:
Grignard and organolithium reagents add twice to acid chlorides and esters to
give alkoxides (Discussed before in alcohol).
b- Nitriles:
A Grignard or organolithium reagent attacks the electrophilic cyano group to
form the salt of an imine. Acidic hydrolysis of the salt gives the imine, which is
further hydrolyzed to a ketone.
1- Acid chlorides
Synthesis
Acid chlorides are best prepared by the action of thionyl chloride (SOCl 2)
or oxalyl chloride (COCl)2 on the acid. Phosphorus trichloride, phosphorus
pentachloride or phosphorus oxychloride can also be used (refer to reaction of
acids).
Reactions of acid chlorides:
2- Acid anhydrides
General anhydride synthesis
The convenient preparation of acid anhydride is through reaction of acid
chlorides with the alkali salt of the acid.
Acetic anhydride (abbreviated AC2O) can also be prepared by passing
acetylene into glacial acetic acid in the presence of mercuric ions as catalyst and
distilling the resulting ethylidene acetate.
Some cyclic anhydrides are made simply by heating the corresponding
diacid. A dehydrating agent, such as acetyl chloride or acetic anhydride, is
occasionally added to accelerate this reaction. Because five- and six-membered
cyclic anhydrides are particularly stable, the equilibrium favours the cyclic
products.
Reactions of anhydrides
Like acid chlorides, anhydrides participate in the Fiedel-Crafts acylation.
Catalysts may be aluminium chloride, polyphosphoric acid (PPA), or other acidic
reagents. Cyclic anhydrides can provide additional functionality on the side chain
of the aromatic product.
In most cases, it is easier and more efficient to make and use acid chlorides
than anhydrides.
Use of cyclic anhydrides to give difunctional compounds. It is often
necessary to convert just one acid group of a diacid to an ester or an amide.
3- Esters
Synthesis of esters
a- Direct esterification of the carboxylic acid.
b- From acid chlorides or anhydrides:
Acid chlorides or anhydrides react rapidly with alcohols to form esters.
These reactions proceed according to this addition-elimination mechanism
mostly quantitative. The reaction with tertiary alcohols is very slow, and is
usually accompanied by side reactions.
c- From the silver salt of the acid:
Esters may be prepared by refluxing the silver salt of an acid with an alkyl halide
in ethanolic solution.
d- Methyl esters:
Are conveniently made by treating the acid with diazomethane.
e- Transesterification:
Substitution of one alkoxy group for another. When an ester is treated with a
different alcohol in the presence of an acid catalyst, the two alcohol groups can
interchange. An equilibrium results, and the equilibrium can be driven toward the
desired ester by using a large excess of the desired alcohol or by removing the
other alcohol.
Transesterification also occurs under basic conditions, catalyzed by a small
amount of alkoxide ion. A large excess of the desired alcohol helps to achieve a
good conversion.
f- Bayer-Villiger oxidation of ketones (refer to ketones).
Reactions of esters
Formation of lactones:
Simple lactones containing five- and six-membered rings are often more
stable than the open-chain hydroxyl acids. Such lactones form spontaneously
under acidic conditions (via an intramolecular Fischer esterification).
Lactones that are not energetically favoured may be synthesized by driving
the equilibrium toward the products. For example, the ten-membered 9hydroxynonanoic acid lactone is formed in a dilute benzene solution containing
a trace p-toluenesulphonic acid. The reaction is driven to completion by distilling
the benzene / water azeotrope to remove water and shift the equilibrium to the
right.
The Claisen ester condensation
It is the reaction of esters containing α-hydrogen atoms under the effect of
a strong base to form β-keto esters. The overall reaction combines two ester
molecules to give a β-ketoester with the expulsion of an alcohol molecule.
The Claisen reaction involves a series of equilibria; the first one is the
formation an ester enolate and since the alkoxide is a weaker base than the
enolate, this equilibrium is unfavourable. The second equilibrium is the acylation
of the second molecule of ester by this enolate (nucleophilic acyl substitution),
and the last one is the deprotonation of the formed β-keto ester with the formation
of its resonance-stabilized enolate anion. In the presence of strong base such as
ethoxide ion or hydroxide ion, it is the last step which derives the reaction to
completion. In practice, the neutral β-keto ester is recovered through acidification
of the reaction mixture.
In the Claisen condensation, a full equivalent of base must be used, because
the base is consumed in the deprotonation step. The importance of this step
explains why esters with only one α-hydrogen atom, e.g. ethyl 2methylpropanoate, fail to undergo this reaction. Generally, the yield of β-keto
esters can be improved by removing the produced alcohol by distillation, this
shifts the equilibrium towards the product.
Crossed Claisen condensation
Claisen condensations can take place between different esters, particularly
when only one of the esters has the α-hydrogens needed to form an enolate.
Crossed Claisen condensations between ketones ans esters are also possible.
Ketones are more acidic than esters, and the ketone component is more likely to
deprotonate and serves as the enolate component in the condensation. Formates,
oxalates and carbonates are devoid of α-hydrogens and commonly used in the
crossed reaction.
4- Amides
Synthesis of amides
Amides are the least receive acid derivatives, and they can be made from
any of the others.
Reactions of amides
Because amides are the most stable acid derivatives, they are not easily
converted to other derivatives by nucleophilic acyl substitution. The most
important reaction is their reduction to amine. The Hofmann rearrangement also
converts amides to amines, with the loss of one carbon atom. Although an amide
is considered a neutral functional group, it is both weakly acidic and weakly basic,
and amides are hydrolysed by strong acid or base.
Dehydration of amides to nitriles
Strong dehydrating agents as phosphorus pentoxide (P2O5) and phosphorus
oxychloride (POCl3) can remove the elements of water from a primary amide to
give a nitrile.
Formation of lactams
Fives-membered lactams (γ-lactams) and six-membered lactams (δlactams) are often form on heating or adding a dehydrating agent to the
appropriate γ-amino acids and δ-amino acids. Lactams containing smaller or
larger rings do not form readily under these conditions.
Chapter 8
Aliphatic Amines
Nomenclature
In common nomenclature most primary amines are named as alkylamines.
In systematic nomenclature (in parenthesis below) they are named by adding the
suffix- amine to the name of the chain or ring system to which the NH 2 group is
attached with elision of the final e.
Primary amines:
CH3NH2
CH3CH2NH2
𝐶𝐻3 𝐶𝐻𝐶𝐻2 𝑁𝐻2
|
𝐶𝐻3
Methylamine
Ethylamine
Isobutylamine
(methanamine)
(ethanamine)
Cyclohexylamine
(2-methyl-1-propanamine) (Cyclohexanamine)
Most secondary and tertiary amines are named in the same general way. In
common nomenclature we either designate the organic groups individually if they
are different, or use the prefixes di- or tri- if they are the same. In systematic
nomenclature we use the locant N to designate substituents attached to a nitrogen
atom.
Secondary amines:
CH3NHCH2CH3
(CH3CH2)2NH
Ethylmethylamine
Diethylamine
(N-methylethanamine)
(N-ethylethanamine)
Tertiary amines:
(CH3CH2)3N
𝐶𝐻2 𝐶𝐻3
|
𝐶𝐻3 𝑁𝐶𝐻2 𝐶𝐻2 𝐶𝐻3
(N,N-diethylethanamine)
Ethylmethylpropylamine
(N-ethyl-N-methyl-1-propanamine)
In the IUPAC system, the substituent ¬NH2 is called the amino group. We often
use this system for naming amines containing an OH group or a COOH group.
H2NCH2CH2OH
H2NCH2CH2COOH
2-aminoethanol
3-aminopropanoic acid
Structure of amines
The nitrogen atom of most amines is like that of ammonia; it is
approximately sp3 hybridized. The three alkyl groups (or hydrogen atoms) occupy
comers of a tetrahedrone; the sp3 orbital containing the unshared electron pair is
directed toward the other comer. We describe the geometry of the amine by the
location of the atoms as being trigonal pyramidal. However, if we were to
consider the unshared electron paired as being a group we describe the amine as
being tetrahedral. The bond angels are what one would expect of a tetrahedral
structure; they are very close to 109.5o. The bond angles for trimethylamine, for
example, are 108o.
If the alkyl groups of a tertiary amine are all different the amine will be
chiral. There will be two enantiometric forms of the tertiary amine bond,
theoretically, we ought to be able to resolve (separate) these enantiomers. In
practice, however, resolution is usually impossible because the enantiomers
interconvert rapidly.
This interconversion occurs through what is called a pyramidal or nitrogen
inversion. The barrier to the interconversion is about 6 Kcal mol-1 for most simple
amines. In the transition state for the inversion, the nitrogen atom becomes sp2
hybridized with the unshared electron pair occupying a p orbital.
Ammonium salts cannot undergo inversion because they do not have an
unshared pair. Therefore, those quaternary ammonium salts with four different
groups are chiral and can be resolved into separate (relatively stable) enantiomers.
Physical properties
Most commonly encountered alkylamines are liquids with unpleasant,
“fishy” odour.
We have seen on a number of occasions that the polar nature of substance
can affect physical properties such as boiling point. This is true for amines, which
are more polar than alkanes but less polar than alcohols. For similarly constituted
compounds, alkylamines have boiling points which are higher than those of
alkanes but lower than those of alcohols.
CH3CH2CH3
CH3CH2NH2
CH3CH2OH
Propane
Ethylamine
Ethanol
μ=0D
μ = 1.2 D
μ = 1.7 D
Bp -42o
Bp 17o
Bp 78o
Dipole-dipole interactions, specially hydrogen bonding, are stronger in
amines than in alkanes. The less polar nature of amines as compared with
alcohols, however, makes these intermolecular forces weaker in amines than in
alcohols.
Among isomeric amines, primary amines have the highest boiling points,
and tertiary amines the lowest.
CH3CH2CH2NH2
CH3CH2NHCH3
(CH3)3N
Propylamine
N-methylethylamine
Trimethylamine
A primary amine
A secondary amine
A tertiary amine
Bp 50o
Bp 34o
Bp 3o
Primary and secondary amines can participate in intermolecular hydrogen
bonding, while tertiary amines cannot.
Amines that have fewer than six or seven carbon atoms are soluble in
water. All amines, even tertiary amines, can act as proton acceptors in hydrogen
bonding to water molecules.
The simplest arylamines, aniline, is a liquid at room temperature and has a
boiling point of 184oc. Almost all other arylamines have higher boiling points.
Aniline is only slightly soluble in water (3 g/100 ml). Substituted derivatives of
aniline tend to be even less water-soluble.
Measures of amine basicity
There are two conventions used to measure the basicity of amines. One of
them defines a basicity constant Kb for the amine acting as a proton acceptor from
water.
Kb = [R3NH+] [HO] / [R3N] and pKb = -log Kb
The basicity of ammonia is given as Kb = 1.8 x 10-5 (pKb = 4.7) on this
scale. A typical amine such as methylamine (CH3NH2) is a stronger base than
ammonia and has Kb = 4.4 x 10-4 (pKb = 3.3).
The other convention relates the basicity of an amine (R3N) to the acid
dissociation constant Ka of its conjugate acid (R3NH+):
Where Ka and pKa have their usual meaning.
Ka = [H+] [R3N] / [R3NH+] and pKa = -log Ka
The conjugate acid of ammonia is ammonium ion (NH4+), which has Ka =
5.6 x 10-10 (pKa = 9.3). The conjugate acid of methylamine is methylammonium
ion (CH3NH3+), which has Ka = 2 x 10-11 (pKa = 10.7). The more basic the amine,
the weaker its conjugate acid. Methylamine is a stronger base than ammonia;
methylammonium ion is a weaker acid than ammonium ion.
The relationship between the equilibrium constant Kb for an amine (R3N)
and Ka for its conjugate acid (R3NH+) is:
KaKb = 10-14
and pKa + pKb = 14
The device of citing amine basicity according to the acidity of its conjugate
acid has the advantage of permitting proton-transfer reaction of amines to be
analysed according to the usual Bronstewd acid-base relationships. By comparing
the acidity of an acid and the conjugate acid of an amine, for example, we see that
amines are converted to ammonium ion by acids even as weak as acetic acid:
Conversely, adding sodium hydroxide to an ammonium salt converts into
the free amine:
Their basicity provides a means by which amines may be separated from
neutral organic compounds. A mixture containing an amine is dissolved in diethyl
ether and shaken with diluted hydrochloric acid to convert the amine to an
ammonium salt. The ammonium salt, being ionic, dissolves in the aqueous phase,
which is separated from the ether layer. Adding sodium hydroxide to the aqueous
layer converts the ammonium salt back to the free amine, which is then removed
from the aqueous phase by extraction with a fresh portion of ether.
Basicity of amines
Amines are weak bases, but as a class amines are the strongest bases of all
neutral molecules. The following table lists basicity data for a number of amines.
The most important relationship to be drawn from the data are:
1. Alkylamines are slightly stronger bases than ammonia.
2. Alkylamines differ very little among themselves in basicity.
Their basicities cover a range of less than 10 in equilibrium constant (one
pK unit).
3. Arylamines are much weaker bases than ammonia and alkylamines. Their
basicity constants are on the order of 106 smaller than those of alkylamines
(six pK units).
Table: Base strength of amines as measured by their basicity constants and the dissociation
constants of their conjugate acids.
Compound
Structure
Basicity
Acidity of conjugate acid
Kb
pKb
Ka
pKa
NH3
1.8 x 10-5
4.7
5.5 x 10-10
9.3
methylamine
CH3NH2
4.4 x 10-4
3.4
2.3 x 10-11
10.6
Ethylamine
CH3CH2NH2
5.6 x 10-4
3.2
1.8 x 10-11
10.8
Isopropylamine
(CH3)2CHNH2
4.3 x 10-4
3.4
2.3 x 10-11
10.6
Tert-butylamine
(CH3)3CNH2
2.8 x 10-4
3.6
3.6 x 10-11
10.4
Aniline
C6H5NH2
3.8 x 10-10
9.4
2.6 x 10-5
4.6
Dimethylamine
(CH3)2NH
5.1 x 10-4
3.3
2.0 x 10-11
10.7
Diethylamine
(CH3CH2)2NH
1.3 x 10-4
2.9
7.7 x 10-12
11.1
N-methylaniline
C6H5NHCH3
6.1 x 10-10
9.2
1.6 x 10-5
4.8
Ammonia
Primary amines
Secondary amines
Tertiary amines
Trimethylamine
(CH3)3N
5.3 x 10-5
4.3
1.9 x 10-10
9.7
Triethylamine
(CH3CH2)3N
5.6 x 10-4
3.2
1.8 x 10-11
10.8
Alkylamines, while most alkylamines are very similar in basicity, it is
generally true that their basicities increase in the order:
NH3
< RNH2
Ammonia
~ R3N
Primary amine
Tertiary amine
(least basic)
< R2NH
Secondary amine
(most basic)
Diethylamine, for example, is more basic than either ethylamine or
trimethylamine, and all these compounds are more basic than ammonia, as
measured in aqueous solution.
Basicity of amines in aqueous solution
NH3
< CH3CH2NH2
~ (CH3CH2)3N
< (CH3CH2)2NH
Ammonia
Ethylamine
Trimethylamine
Diethylamine
Kb 1.8 x 10-5
Kb 5.6 x 10-4
Kb 5.6 x 10-4
Kb 1.3 x 10-3
(pKb 4.7)
(pKb 3.2)
(pKb 3.2)
(pKb 2.9)
The discontinuity in basicity among the various classes of amines suggests
that there are at least two substituent effects involved and that they operate in
opposite directions.
An alkyl group can increase the base strength of an amine by releasing
electrons to nitrogen. The positive charge of an ammonium ion is dispersed better
by having alkyl groups instead of hydrogen as substituents on nitrogen.
By stabilizing the ammonium ion, alkyl groups increase the equilibrium
constant for amine protonation.
Were this the only effect of alkyl group, the basicity of amines would
increase with increasing alkyl substitution. Indeed, this is precisely what is
observed for proton transfer to amines in the gas phase.
Gas-phase basicity of amines
NH3
Ammonia
< CH3CH2NH2
< (CH3CH2)2N
< (CH3CH2)3NH
Ethylamine
Diethylamine
Trimethylamine
(least basic)
(most basic)
Electron release from alkyl groups provides the principal mechanism by
which the conjugate acid of an amine is stabilized in the gas phase. The more the
alkyl groups that are attached to the positively charged nitrogen, the more stable
the alkyl ammonium ion becomes.
Basicity as measured by Kb, however, refers to equilibrium measurements
made in dilute aqueous solution. The altered order of amine basicities in solution,
as compared with those in the gas phase, must arise from salvation effects. While
alkyl substituents increase the ability of an ammonium ion to disperse its positive
charge, they decrease its ability to form hydrogen bonds to water molecules.
Dialkylammonium ions, formed by protonation of secondary amines, have two
hydrogen substituents on nitrogen that can participate in hydrogen bonding.
Trialkylammonium ions have only one and are therefore less stabilized by
salvation than are their dialkyl counterparts.
Dialkylamines are slightly more basic than either primary or tertiary
amines because their conjugate acids possess the best combination of alkyl and
hydrogen substituents to permit stabilization both by electron release from alkyl
groups and by solvation due to hydrogen bonding.
Preparation of amines
1- Through nucleophilic substitution reactions:
Salts of primary amines can be prepared from ammonia and alkyl halides by
nucleophilic substitution reactions. Subsequent treatment of the resulting a
minimum salt with base gives primary amines.
This method is very limited synthetic application because multiple
alkylations occur. When ethyl bromide reacts with ammonia, for example, the
minimum bromide that is produced initially can react with ammonia to liberate
ethylamine.
Ethylamine can then compete with ammonia and react with ethyl bromide
to give diethylaminium bromide. Repetitions of acid-base and alkylation
reactions ultimately produce some tertiary amines and even some quaternary
ammonium salts if the alkyl halide is present in excess.
Multiple alkylations can be minimized by using a large excess of ammonia.
(Why?). An example of this technique can be seen in the synthesis of alanine
from 2-bromopropanoic acid:
A much better method for preparing a primary amine from an alkyl halide
is first to convert the alkyl halide to an alkyl azide (R-N3) by a nucleophilic
substitution reaction:
Then the alkyl azide can be reduced to a primary amine with sodium and
alcohol or with lithium aluminium hydride. A word of caution: alkyl azides are
explosive and low molecular weight alkyl azides should not be isolated but should
be kept in solution.
Potassium phthalimide (see the following reaction) can also be used to
prepare primary amines by a method known as the Gabriel synthesis. This also
avoids the complications of multiple alkylations that occur when alkyl halides are
treated with ammonia:
Phthalimide is quite acids (pKa = 9); it can be converted to potassium
phthalimide by potassium hydroxide (step 1). The phthalimide anion is a strong
nucleophile and (in step 2) it reacts with an alkyl halide to give an Nalkylphthalimide. At this point, the N-alkylphthalimide can be hydrolyzed with
aqueous acid or base, but the hydrolysis is often difficult it is often more
convenient to treat the N-alkylphthalimide with hydrazine (NH2NH2) in refluxing
ethanol (step 3) to give a primary amine and phthalazin-1,4-dione.
Synthesis of amines using the Gabriel synthesis are, as we might expect,
restricted to the use of methyl, primary, and secondary alkyl halides. The use of
tertiary halides almost exclusively to eliminations.
Multiple alkylations are not a problem when tertiary amines are alkylated
with methyl or primary halides. Reactions such as the following take place in
good yield.
2- Through reduction of nitro compounds:
The most widely used method for preparing aromatic amines involves nitration
of the ring and subsequent reduction of the nitro group to an amino group.
Reduction of the nitro group can also be carried out in a number of ways.
the most frequently used methods employ catalytic hydrogenation, or treatment
of the nitro compound with acid and iron (zinc, or tin, or a metal salt such as
SnCl2 can also be used).
3- Through reductive amination:
Aldehydes and ketones can be converted to amines through catalytic or chemical
reduction in the presence of ammonia or an amine. Primary, secondary, and
tertiary amines can be prepared this way.
This process, called reductive amination of the aldehyde or ketone (or
reductive alkylation of the amine), appears to proceed through the following
general mechanism (illustrated with a 1o amine):
When ammonia or a primary amine is used, there are two possible
pathways to the product via an amino alcohol that is similar to a hemiacetaland is
called a hemiaminal, or via an imine. When secondary amines are used, an imine
cannot form and, therefore, the pathway is through the hemiaminalor through an
iminium ion.
The reduction agents employed include hydrogen and a catalyst (such as
nickel), or NaBH3CN or LiBH3CN. The latter two reducing agents are similar to
NaBH4 and are especially effective in reductive aminations.
4- Through reduction of amides, oximes, and nitriles:
Amides, oximes, and nitriles can be reduced to amines. Reduction of a nitrile or
an oxime yields a primary amine; reduction of an amide can yield a primary,
secondary, or tertiary amine.
In the last example, if R’ and R’’ = H, the product is a 1o amine; if R’ = H,
the product is a secondary amine). All of these reactions can be carried out with
hydrogen and a catalyst or with LiAlH4. Oximes are also congenitally reduced
with sodium in alcohol – a safer method than the use of LiAlH4 sepcific examples
follow:
Reduction of an amide is the last step in a useful procedure for
monoalkylation of an amide. The process begins with acylation of the amine
using an acyl chloride or acid anhydride; then the amide is reduced with LiAlH 4
for example,
5- Through the Hofmann and curtius rearrangements:
Amides with no substituents on the nitrogen react with solutions of bromine or
chlorine in sodium hydroxide to yield amines through a reaction known as the
Hofmann rearrangement or Hofmann degradation:
𝐻2 𝑂
𝑅𝐶𝑂𝑁𝐻2 + 𝐵𝑟2 + 4𝑁𝑎𝑂𝐻 →
𝑅𝑁𝐻2 + 2𝑁𝑎𝐵𝑟 + 𝑁𝑎2 𝐶𝑂3 + 2𝐻2 𝑂
From this equation we can see that the carbonyl carbon atom of the amide
is lost (as CO32-) and that the R group of the amide becomes attached to the
nitrogen of the amine. Primary amines made this way are not contaminated by
secondary or tertiary amines.
The mechanism for this interesting reaction is shown below. In the first
two step the amide undergoes a base-promoted bromination, in a manner
analogue to the base-promoted halogenation of a ketone (The electronwithdrawing acyl group of the amide makes the amido proton much more acidic
than those of an amine).
The N-bromoamide then reacts with hydroxide ion to produce an anion,
which spontaneously rearranges with the loss of a bromide ion to produce an
isocyanate. In the rearrangement the R group migrates with its electrons from the
acyl carbon to the nitrogen atom at the same time the bromide ion departs. The
isocyanate that forms in the mixture is quickly hydrolysed by the aqueous base to
a carbamateionm which undergoes spontaneous decarboxylation resulting in the
formation of the amine.
An examination of the first two steps of this mechanisms shows that,
initially, two hydrogen atoms must be present on the nitrogen of the amide for the
reaction to occur. Consequently, the Hofmann rearrangement is limited to amides
of the type RCONH2. Studies of Hofmann rearrangement of optically active
amides in which the stereocentre is directly attached to carbonyl group have
shown that these reactions occur with retention of configuration. Thus, the R
group migrates to nitrogen with its electron, but without inversion.
The Curtius rearrangement is a rearrangement that occurs with acyl azides.
It resembles the Hofmann rearrangement in that an R- group migrates from the
acyl carbon to the nitrogen atom as the leaving group departs. In this instance the
leaving group is N2 (the best of all possible leaving groups since it is highly stable,
virtually non-basic, and being a gas removes itself from the medium). Acyl azides
are easily prepared by allowing acyl chlorides to react with sodium azides.
Heating the acyl azides bring about the rearrangement; afterwards, adding water
causes hydrolysis and decarboxylation of the isocyanate.
Reactions of amines
Both the basicity and nucleophilicity of amines originate in the unshared
electron pair of nitrogen. When an amine acts as a base, this electron pair abstracts
a proton from a Bronsted acid. When an amine acts as nucleophile, the first step
is the attack of the unshared electron pair on the positively charged carbon of a
carbonyl group.
1- Reaction of amine with alkyl halides:
Nucleophilic substitution results when primary alkyl halides are treated with
amines.
A second alkylation may follow, converting the secondary amine to a
tertiary amine. Alkylation need not stop there; the tertiary amine may itself be
alkylated, giving a quaternary ammonium salt.
𝑅′𝐶𝐻2 𝑋
𝑅′𝐶𝐻2 𝑋
𝑅′𝐶𝐻2 𝑋
𝑅𝑁𝐻2 →
𝑅𝑁𝐻𝐶𝐻2 𝑅′ →
𝑅𝑁(𝐶𝐻2 𝑅′ )2 →
𝑅𝑁 + (𝐶𝐻2 𝑅′ )3 𝑋 −
Primary
Secondary
Tertiary
Quaternary
Amine
Amine
Amine
Ammonium salt
Because of its high reactivity toward nucleophilic substitution, methyl
iodide is the alkyl halide most frequently encountered in amine alkylations
designed to proceed to the quaternary ammonium salt stage.
Quaternary ammonium salts, as we have seen, are useful in synthetic
organic chemistry as phase-transfer catalysts. In another, more direct application,
quaternary ammonium hydroxides are used as substrates in an elimination
reaction to form alkenes.
2- Reaction of amines with aldehydes and ketones:
Discussed before in aldehydes and ketones.
3- Reaction of amines with acyl chlorides:
Mentioned before in carboxylic acids and their derivatives.
4- The Hofmann elimination:
The halide anion of quaternary ammonium iodides may be replaced by hydroxide
by treatment with an aqueous slurry of silver oxide. Silver iodide precipitates, and
a solution of the quaternary ammonium hydroxide is formed
When quaternary ammonium hydroxides are heated, they undergo βelimination to form an alkene and an amine.
This reaction is known as the Hofmann elimination; it was developed by
August W. Hofmann in the med-nineteenth century and is used both as a synthetic
method to prepare alkenes and as a degradative tool for structure determination.
A novel aspect of the Hofmann elimination is its regioselectivity
elimination alkyltrimethylammonium hydroxides proceeds in the direction that
gives the less substituted alkene.
It is less sterically hindered β hydrogen that is removed by the base in
Hofmann elimination reactions. Methyl groups are deprotonated in preference to
methylene groups, and methylene groups are deprotonated in preference to
methines. The regioselectivity of Hofmann elimination is opposite to that
predicted by the Zaitsev rule. Base-promoted elimination reactions of
alkyltrimethylammonium salts are said to obey the Hofmann rule; they yield the
less substituted alkene.
5- Reaction of amines with nitrous acid:
When solutions of sodium nitrite (NaNO2) are acidified, a number of specie are
formed that act as nitrosating agents. That is, they react as sources of nitrosyl
cation. In order to simplify discussion, organic chemists group all of these species
together and speak of the chemistry of one of them, nitrous acid, as a generalized
precursor to nitrosyl cation.
Nitrosating of amines is best illustrated by examining what happens when
a secondary amine “reacts with nitrous acid”. The amine acts as nucleophile,
attacking the nitrogen of the nitrosyl cation.
The intermediate that is formed in the first step losses a proton to give an
N-nitroso amine as the isolated product.
N-nitroso amines are more often called nitronitrosamines, and because
many of them are potent carcinogens, they have been the object of much recent
investigation. We encounter nitrosamines in the environment on a daily basis. A
few of these, all of which are known carcinogens, are illustrated:
Nitrosamines are formed whenever nitrosating agents come in contact with
secondary amines. Indeed, more nitrosamines are probably synthesized within
our body than enter it by environmental contamination. Enzyme-catalyzed
reduction of nitrate (NO3¬) produces nitrite (NO2¬), which combines with amines
present in the body to form N-nitrosoamines. When primary amines are
nitrosated, the N-nitroso compounds produced can react further.
The product of this sequence of steps in an alkyldiazonium ion. The amine,
in being converted to a diazonium ion, is said to have been diazotized. Alkyl
diazonium ions are not very stable, usually decomposing rapidly under the
conditions of their formation. Molecular nitrogen is a leaving group par
excellence, and the reaction products arise by solvolysis of the diazonium ion.
Usually, a carbocation intermediate is involved.
Since nitrogen-free products result from the formation and decomposition
of the diazonium ion, these reactions are often referred to as deamination
reactions. Alkyl diazonium ions are rarely used in synthetic work but have been
studied extensively to probe the behaviour of carbocations generated under
conditions in which the leaving group is lost rapidly and irreversibly.
6- Reaction of amines with sulphonyl chlorides:
Primary and secondary amines react with sulphonyl chlorides to form
sulphonamides.
When heated with aqueous acid, sulphonamides are hydrolysed to amines.
This hydrolysis is much slower, however, the hydrolysis of carboxamide.
7- The Hinsberg test:
Sulphonamide formation is the basis for a chemical test, called the Hinsberg test,
that can be used to demonstrate whether an amine is primary, secondary, or
tertiary. A Hinsberg test involves two steps. First, a mixture containing a small
amount of the amine and benzenesulphonyl chloride is shaken with excess
potassium hydroxide. Next, after allowing time for a reaction to take place, the
mixture is acidified. Each type of amine gives a different set of visible results
after each of these two stages of the test.
Primary amines react with benzenesulphonyl chloride to forn N-substituted
benzenesulphonamides. These, in turn, undergo acid-base reactions with the
excess potassium hydroxide to form water soluble potassium salts. (These
reactions take place because the hydrogen attached to nitrogen is made acidic by
the strongly electron-withdrawing ¬SO2 group). At this stage our test tube will
contain a clear solution. Acidification of this solution will, in the next stage, cause
the water-insoluble N-substituted sulphonamide to precipitate.
Secondary amines react with benzenesulphonyl chloride in aqueous
potassium hydroxide to form insoluble N,N-disubstituted sulphonamides that
precipitated after the first stage. N,N-disubstituted sulphonamides do not dissolve
in aqueous potassium hydroxide because they do not have an acidic hydrogen.
Acidification of the mixture obtained from secondary amine produces no visible
result (the non-basic N,N-disubstituted sulphonamide remains as a precipitate and
no new precipitate forms.
If the amine is a tertiary amine and if it is water insoluble, no apparent
change will take place in the mixture as we shake it with benzenesulphonyl
chloride and aqueous KOH. When we acidify the mixture, the tertiary amine will
dissolve because it will form a water-soluble salt.
Chapter 9
Aromatic Compounds
Introduction
1. The study of aromatic compounds began with the discovery in 1825 of a
new hydrocarbon by the English chemist Michael Faraday (Royal
Institution).
1) Faraday isolated benzene from a compressed illuminating gas that had
been made by pyrolyzing whale oil.
2) In 1834 the German chemist Eilhardt Mitscherlich (University of
Berlin) synthesized benzene by heating benzoic acid with calcium
oxide.
i-
Using vapour density measurements Mitscherlich further showed
that benzene has the molecular formula C6H6.
ℎ𝑒𝑎𝑡
ii-
𝐶6 𝐻5 𝐶𝑂2 𝐻 + 𝐶𝑎𝑂 →
𝐶6 𝐻6 + 𝐶𝑎𝐶𝑂3
Benzoic acid
benzene
Benzene has only as many hydrogen atoms as it has carbon
atoms.
iii-
Benzene with formula of C6H6 (or CnH2n-6) should be a highly
unsaturated compound, because it has an index of hydrogen
deficiency equal to four.
3) Eventually, chemists began to recognize that benzene was a member of
a new class of organic compounds with unusual and interesting
properties.
2. During the latter part of the nineteenth century the Kekule-CouperButlerov theory of valence was systematically applied to all known organic
compounds.
1) Organic compounds were classified as being either aliphatic or
aromatic.
i-
Aliphatic meant that the chemical behaviour of a compound was
“fatlike”. (Now it means that the compound reacts like an alkane,
an alkene, an alkyne, or one of their derivatives).
ii-
Aromatic meant that the compound has a low hydrogen / carbon
ratio and that it was “fragrant”.
a. Most of the early aromatic compounds were obtained from
balsams, resins, or essential oils.
b. Among these were benzaldehyde (from oil of bitter almonds),
benzoic acid and benzyl alcohol (from gum benzoin), and
toluene (from tolu balsam).
2) Kekule was the first to recognize that these early aromatic compounds
all contain a six-carbon unit and that they retain this six-carbon unit
through most chemical transformations and degradations.
3) Benzene was eventually recognized as being the parent compound of
this new series.
Nomenclature of benzene derivatives
1. Two systems are used in naming monosubstituted benzenes.
1) In certain compounds, benzene is the parent name and the substituent is
simply indicated by a prefix.
2) For other compounds, the substituent and the benzene ring taken
together may form a new parent name.
(i)
Methylbenzene is called toluene.
(ii)
Hydroxybenzene is called phenol.
(iii)
Aminobenzene is called aniline.
3) When two substituents are present, their relative positions are indicated
by the prefixes ortho, meta, and para (abbreviated o-, m-, and p-) or by
the use of numbers.
4) If more than two groups are present on the benzene ring, their positions
must be indicated by the use of numbers.
i-
The benzene ring is numbered so as to give the lowest possible
numbers to the substituents.
ii-
When more than two substituents are present and the substituents
are different, they are listed in alphabetical order.
5) When a substituent is one that when taken together with the benzene
ring gives a new base name, that substituent is assumed to be in position
1 and the new parent name is used:
6) When the C6H5-group is named as a substituent, it is called a phenyl
group.
i-
A hydrocarbon composed of one saturated chain and one benzene
ring is usually named as a derivative of the larger structural unit.
ii-
If the chain is unsaturated, the compound may be named as a
derivative of that chain, regardless of ring size.
7) The phenyl group is often abbreviated as C6H5-, Ph-, or O-.
8) The name benzyl is an alternative name for the phenylmethyl group. It
is sometimes abbreviated Bn.
Chemical reactions of aromatic compounds
Electrophilic aromatic substitution:
 Arene (Ar-H) is the generic term for an aromatic hydrocarbon.
 The aryl group (Ar) is derived by removal of a H atom from an arene.
A general mechanism for electrophilic aromatic substitution: arenium ion
intermediates:
Benzene reacts with an electrophile using two of its π electrons. This first
step is like an addition to an ordinary double bond.
In step 1: the electrophile reacts with two π electrons from the aromatic ring.
The arenium ion is stabilized by resonance which delocalizes the charge.
In step 2: a proton is removed and the aromatic system is regenerated.
The energy diagram of this reaction shows that the first step is highly endothermic
and has large ∆G (1). The second step is highly exothermic and has a small ∆G
(2).
1- Halogenation of benzene:
Halogenation of benzene requires the presence of a Lewis acid.
 Fluorination occurs so rapidly it is hard to stop at mono-fluorination of the
ring (A special apparatus is used to perform this reaction).
 Iodine is so unreactive that an alternative method must be used.
2- Nitration of benzene:
Nitration of benzene occurs with a mixture of concentrated nitric acid and
sulphuric acid. (The electrophile for the reaction is the nitronium ion (NO2+).
3- Sulphonation of benzene:
 Sulphonation occurs most rapidly using fuming sulphuric acid
(concentrated sulphuric acid that contains SO3). Sulphonation also occurs
in conc. sulphuric acid, which contains small quantities of SO 3, as shown
in step 1 below, but more slowly.
 Sulphonation is an equilibrium reaction; all steps involved are equilibria.
 De-sulphonation can be accomplished using dilute sulphuric acid (i.e. with
a high concentration of water).
4- Friedel-Crafts alkylation:
 An aromatic ring can be alkylated by an alkyl halide in the presence of a
Lewis acid (The Lewis acid serve to generate a carbocation electrophile).
 Primary alkyl halides probably do not form discrete carbocations but the
primary carbon in the complex develops considerable positive charge.
 Any compound that can form a carbocation can be used to alkylate an
aromatic ring.
5- Friedel-Crafts acylation:
 An acyl group has a carbonyl attached to some R group.
 Friedel-Crafts acylation requires reaction of an acid chloride or acid
anhydride with a Lewis acid such as aluminium chloride.
 Acid chlorides are made from carboxylic acids.
 The electrophile in Friedel-Crafts acylation is an acylium ion.
 The acylium ion is stabilized by resonance.
Limitations of Friedel-Crafts reactions:
 In Friedel-Crafts alkylation, the alkyl carbocation intermediate
 Powerful electron-withdrawing groups make an aromatic ring much less
reactvie toward Friedel-Crafts alkylation or acylation.
Amino groups also make the ring less reactive to Friedel-Crafts reaction
because they become electron-withdrawing groups upon Lewis acid-base
reaction with the Lewis acid catalyst.
 Aryl and vinyl halides cannot be used in Friedel-Crafts reactions because
they do not form carbocations readily.
 Polyalkylation occurs frequently with Friedel-Crafts alkylation because the
first alkyl group introduced activates the ring toward further substitution.
(Polyacylation does not occur because the acyl group deactivates the
aromatic ring to further substitution).
Synthesis applications of Friedel-Crafts acylations:
The Clemmensen reduction:
 Primary alkyl halides often yield rearranged products in Friedel-Crafts
alkylation which is a major limitation of this reaction.
 Unbranched alkylbenzenes can be obtained in good yield by acylation
followed by Clemmnesen reduction. (Clemmensen reduction reduces
phenyl ketones to the methylene (CH2) group.
 This method can be used to add a ring to an aromatic ring starting with a
cyclic anhydride. (Note that the Clemmensen reagents do not reduce the
carboxylic acid).
Effects of substituents on reactivity and orientation:
 The nature of groups already on an aromatic ring affect both the reactivity
and orientation of future substitution.
 Activating groups cause the aromatic ring to be more reactive than
benzene.
 Deactivating groups cause the aromatic ring to be less reactive than
benzene.
 Ortho-para directors direct future substitution to the ortho and para
positions.
 Meta directors direct future substitution to the meta position.
Activating groups: Ortho-para directors:
 All activating groups are also ortho-para directors. (The halides are also
ortho-para directors but are mildly deactivating).
 The methyl group of toluene is an ortho-para director. (Toluene reacts more
readily than benzene, e.g. at a lower temperature than benzene).
 The methyl group of toluene is an ortho-para director.
 Amino and hydroxyl groups are also activating and ortho-para directors.
(These groups are so activating that catalysts are often not necessary).
 Alkyl groups and heteroatoms with one or more unshared electron pairs
directly bonded to the aromatic ring will be ortho-para directors.
Deactivating groups: Meta directors:
 Strong electron-withdrawing groups such as nitro, carboxyl, and sulfonate
are deactivators and meta directors.
Halo substituents: Deactivating ortho-para directors:
 Chloro and bromo groups are weakly deactivating but are also ortho, para
directors. (In electrophilic substitution of chlorobenzene, the ortho and
para poducts are major):
Reaction
Ortho product Para product Total
ortho Meta product
(%)
(%)
and para (%)
(%)
Chlorination
39
55
94
6
Bromination
11
87
98
2
Nitration
30
70
100
100
100
Sulfonation
Classification of substituents:
Theory of substituent effects on electrophilic substitution:
 Reactivity: the effect of electron-releasing and electron-withdrawing
groups.
 Electron-releasing groups activate the ring toward further reaction.
Electron-releasing groups stabilize the transition state of the first step of
substitution and lead to lower ∆G# and faster rates of reaction.
 Electron-withdrawing groups deactivate the ring toward further reaction.
Electron-withdrawing groups destabilize the transition state and lead to
higher ∆G# and slower rates of reaction.
 The following free-energy profiles compare the stability of the first
transition state in electrophilic substitution when various types of
substituents are already on the ring.
Inductive and resonance effects: Theory of orientation:
 The inductive effect of some substituent Q arises from the interaction of
the polarized bond to Q with the developing positive charge in the ring as
an electrophile reacts with it.
 The following are some other groups that have an electron-withdrawing
effect because the atom directly attached to the ring has a partial or full
positive charge.
 The resonance effect of Q refers to its ability to increase or decrease the
resonance stabilization of the arenium ion.
 Electron-donating resonance ability is summarized below.
Meta-directing groups:
 All meta-directing groups have either a partial or full positive charge on
the atom directly attached to the aromatic ring.
 The trifluoromethyl group stabilizes the arenium ion intermediate in ortho
and para substitution pathways. (The arenium ion resulting from meta
substitution is not so destabilized and therefore mera substitution is
favoured.
Ortho-para directing groups:
 Many ortho-para directors are groups that have a lone pair of electrons on
the atom directly attached to the ring.
 Activating groups having unshared electrons on the atom bonded to the
ring exert primarily a resonance effect.
 The aromatic ring is activated because of the resonance effect of these
groups.
 They are ortho-para directors because they contribute a fourth important
resonance form which stabilizes the arenium ion in the cases of ortho and
para substitution only.
 The fourth resonance form that involves the heteratom is particularly
important because the octet rule is satisfied for all atom in the arenium ion.
Halo groups are ortho-para directors but are also deactivating
 The electron-withdrawing inductive effect of the halide is the primary
influence that deactivates haloaromatic compounds toward electrophilic
aromatic substitution.
 The electron-donating resonance effect of the halogen’s unshared electron
pairs is the primary ortho-para directing influence.
Ortho-para direction and reactivity of alkylbenzenes:
 Alkyl groups activate aromatic rings by inductively stabilizing the
transition state leading to the arenium ion.
 Alkyl groups are ortho-para directors because they inductively stabilize
one of the resonance forms of the arenium ion in ortho and para
substitution.
Reaction of the side chain of alkylbenzenes:
Benzylic radicals and cations:
 When toluene undergoes hydrogen abstraction from its methyl group it
produces a benzyl radical.
 Departure of a leaving group by an SN1 process from a benzylic position
leads to formation of a benzylic cation.
 Benzylic radicals and cations are stabilized by resonance decolarization of
the radical and positive charge, respectively.
Halogenation of the side chain: benzylic radicals:
 Benzylic halogenation takes place under conditions which favour radical
reactions.
 Reaction of N-bromosuccinamide with toluene in the presence of light
leads to allylic bromination.
 Reaction of toluene with excess chlorine can produce multiple benzylic
chlorination.
When ethylbenzene or propylbenzene react under radical conditions,
halogenation occurs primarily at the benzylic position.
Alkenylbenzenes
Stability of conjugated alkenylbenzenes
 Conjugated alkenyl benzenes are more stable than non-conjugated
alkenylbenzenes.
 Additions proceed through the most stable benzylic radical or benzylic
cation intermediates.
Oxidation of the side chain
Alkyl and unsaturated side chains of aromatic rings can be oxidized to the
carboxylic acid using hot KMnO4.
Synthetic applications
 When designing a synthesis of substituted benzenes, the order in which the
substituents are introduced is crucial.
 Examples: synthesize ortho-, meta-, and para-nitrobenzoic acid from
toluene.
Use of protecting and blocking groups
 Strong activating groups such as amine and hydroxyl cause the aromatic
ring to be so reactive that unwanted reactions can take place.
 These groups activate aromatic rings to oxidation by nitric acid when
nitration is attempted; the ring is destroyed.
 An amino group can be protected (and turned into a moderately activating
group) by acetylation.
 Examples: the synthesis of p- and o-nitroaniline from aniline.
 A sulfonic acid group is used as a blocking group to force ortho
substitution.
Orientation in disubstituted benzenes
 When two substituents are present on the ring initially, the more powerful
activating group generally determines the orientation of subsequent
substitution.
 Ortho-para directors determine orientation over meta directors.
 Substitution does not occur between meta substituents due to steric
hindrance.
Allylic and benzylic halides in nucleophilic
Substitution reactions:
Allylic and benzylic halides are classified in similar fashion to other
halides.
 Both primary and secondary allylic and benzylic halides can undergo SN1
or SN2 reaction. These primary halides are able to undergo S N1 reaction
because of the added stability of the allylic and benzylic carbocation.
 Tertiary
Reduction of aromatic compounds