NATIONAL QUALIFICATIONS CURRICULUM SUPPORT
Chemistry
Organic Synthesis Notation
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ORGANIC SYNTHESIS NOTATION (AH CHEMISTRY)
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Contents
‘Curly arrow’ notation
4
Bond fission
5
Homolytic fission
6
Heterolytic fission
8
Electrophiles and nucleophiles
8
Nucleophilic substitition
9
S N 1 reaction mechanisms
10
S N 2 reaction mechanisms
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ORGANIC SYNTHESIS NOTATION
Organic synthesis notation
The synthesis of organic molecules consists of the construction of compounds
via organic reactions. Although some organic molecules can be simple to
construct and design, some complex compounds can require many reaction
steps to sequentially build the desired molecule. It is important that we can
identify some steps common to most reactions and that we are able to
represent these reactions in a manner that is recognised by most chemists.
‘Curly arrow’ notation
All chemical reactions involve the breaking and making of bonds. The way
that bonds break has an important bearing on the direction a reaction will take
and on the mechanism of that reaction. In order to represent an organic
reaction mechanism diagrammatically and to give an impression of bonds
breaking and bonds being made we use curly arrows. Despite their quaint
name, curly arrows are an important part of showing how bonds are formed
and broken, being used specifically to show the movement of electrons, both
singly and in pairs. Curly arrows should not be used for any other purpose in
organic chemistry.
shows the movement of an electron pair (double -headed arrow)
shows the movement of a single electron (single -headed arrow)
In both cases, the arrow tail starts from where the electro n pair/electron
originates and the arrow head points to where the electron pair/electron
finishes. We can illustrate this with the reaction between ethene and hydrogen
bromide.
Remember that a covalent bond is formed by the sharing of electrons and can
be denoted either by a solid line representing a bond or by the two dots
representing the electrons themselves, for example:
H–Br or H:Br
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ORGANIC SYNTHESIS NOTATION
The reaction between ethene and hydrogen bromide is:
C 2 H 4 + HBr
CH 3 CH 2 Br
The electrons move from the ethene and a new bond
forms with the hydrogen from the hydrogen bromide. At
the same time the pair of electrons in the hydrogen
bromide bond moves to the bromine atom. This is shown
here using the curly arrow notation. Note that the head of
the arrow points between the carbon and hydrogen as that
is where the new bond is formed. It is not necessary to show the electrons
themselves since the bond is shown instead.
The second stage of this reaction allows us to illustrate
how to use curly arrows for a lone pair of electrons.
H
+
H2C
C
The first stage of the reaction has left us with a positive
charge on one carbon and a negative bromide ion.
Remember there are another three lone pairs of
H
electrons on the outside of the bromide ion but these are H
Br
not required to be shown as they are not involved in the
bond-making process. However, you must show the lone pair tha t you are
interested in as a pair of dots. Once again, notice that the head of the arrow is
pointing to a place between the carbon and the bromide ion since this is
where the bond is formed.
You will be required to represent many reactions using cur ly arrows and you
will find some examples in the next section that utilise curly arrows to
represent the movement of both electron pairs and single electrons.
Bond fission
In organic chemical reactions covalent bonds are created and broken. Bond
breaking is also known as bond fission. There are two ways in which bond
fission can happen: homolytic (homo from Latin meaning the same) and
heterolytic (hetero from Latin meaning different) fission.
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ORGANIC SYNTHESIS NOTATION
Homolytic fission
In this type of bond fission, the two shared electrons separate equally, one
going to each atom:
H
:
H• + •Br
Br
(Remember the single-headed arrow,
electron.)
, shows movement of only one
The dot• beside each atom represents the unpaired electron that t he atom has
retained from the shared pair in the bond. The atoms are electrically neutral
because each has equal numbers of protons and electrons. However, the atoms
are highly reactive because the unpaired electron has a strong tendency to
pair up with another electron from another atom or molecule.
Such highly reactive atoms or groups of atoms containing unpaired electrons
are called free radicals and because of their high reactivity they exist only as
reaction intermediates.
Free radicals are most likely to be formed when the bond being broken is
non-polar, i.e. it has electrons that are more or less equally shared.
One reaction that you have previously studied at Higher level is the
substitution reaction between methane and chlorine, in which one of the
hydrogen atoms in methane is replaced by a chlorine atom. This is a freeradical chain reaction and is a good example of where we can use both free
radicals and curly arrows to help understand the mechanism.
In the initiation step, UV light is required to split the chlorine molecules into
two chlorine free radicals:
UV
Cl
:
Cl• + •Cl (or 2Cl•)
Cl
The propagation step involves two steps that allow this reaction to be classed
as a chain reaction. Firstly, a chlorine radical can collide with a methane
molecule, resulting in the removal of a hydrogen atom:
H
H
C
H
H +
•Cl
H
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H
C + H : Cl
H
ORGANIC SYNTHESIS NOTATION
A methyl radical, CH 3 , is produced and, in the second step, collide s with
another chlorine molecule that has not been split up by the UV light,
producing more chlorine radicals, which keep the reaction repeating:
H
H
H
C
H
Cl—Cl
+
Cl + •Cl
C
H
H
There are three possible termination steps, all of which remove the radicals
from the process.
1.
Cl•
+
•Cl
Cl : Cl
H
2.
H
C
H
+
•Cl
H
C
H
H
H
3.
H
C
H
Cl
+
H
H
H
C
C
H
H
H
The overall process is known as free-radical substitution or a free-radical
chain reaction.
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ORGANIC SYNTHESIS NOTATION
Heterolytic fission
If, when the bond breaks, one atom retains both of the electrons from the
former covalent bond then an ion pair is formed , for example:
H
:
H + + :Br –
Br
(Note that the curly arrow here is double headed since it indicates that a pair
of electrons has shifted.)
Heterolytic fission is more likely when a bond is already polar. For example,
bromomethane contains a polar C–Br bond, and under certain conditions this
can break heterolytically:
H
H
C
+
+ Br –
H
It should be noted that the CH 3 + ion contains a positively charged carbon
atom. The CH 3 + ion is an example of a carbocation (also called a carbonium
ion). Sometimes heterolytic fission can lead to the formation of ions
containing a negatively charged carbon atom. These ions are called
carbanions. Generally speaking, both these types of ions tend to be unstable
and highly reactive. Consequently, they only exist as short -lived reaction
intermediates.
Electrophiles and nucleophiles
In reactions involving heterolytic bond fission, attacking groups are classified
as nucleophiles or electrophiles.
Nucleophile means ‘nucleus-loving’ and nucleophiles are electron-rich
species that seek out an electron-deficient site, for example OH − , Cl − , Br − ,
CN − , NH 3 and H 2 O. They are atoms or groups of atoms that are attracted
towards atoms bearing a positive charge, capable of donating and sharing
electrons to form a new bond. Nucleophiles may be uncharged molecules or
negative ions, but must have at least one lone pair of electrons .
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ORGANIC SYNTHESIS NOTATION
Electrophile means ‘electron-loving’ and these are electron-deficient species,
for example H + , Cl + , Br + , I+ , NO 2 + , CH 3 + and CH 3 CO + . They are usually
positive ions or uncharged molecules, with one atom that has a slightly
positive charge, such as the S in SO 3 .
+
H3C
electrophile

Br
nucleophile
The terms electrophile and nucleophile do not apply only to ions. Partial
negative and positive charges can be found in many organic compounds that
are polar. These partial charges can also act as electrophilic or nucleophilic
centres.
Halogen atoms generally have a higher electronegativity than carbon and so it
is reasonable to expect that the C–X bond in the haloalkane will be polarised,
with the carbon atom carrying a partial positive charge. This means that this
carbon atom will be susceptible to attack by nucleophiles. If the C –X bond
breaks heterolytically, an X − ion will be formed. Chloride, bromide and
iodide ions are all stable ions and are regarded as good leaving groups. This
means that the presence of these atoms in a molecule will fa cilitate the
heterolytic fission of the bond. In general, a nucleophilic substitution reaction
can be represented as shown below, where Y − represents the attacking
nucleophile and X − is the leaving group.
In fact, nucleophilic substitution can occur by either of two distinctly
different mechanisms.
Nucleophilic substitution
Nucleophilic substitution is simply a reaction in which an attacking
nucleophile replaces a leaving group. Nucleophilic substitution reactions fall
into two categories: S N 1 or S N 2. In order to determine which mechanism
applies to an organic compound we must look at the structure of the carbon
skeleton.
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ORGANIC SYNTHESIS NOTATION
S N 1 reaction mechanisms
A common example of this reaction mechanism is the reaction of 2-bromo-2methylpropane with hydroxide ions using a solvent of aqueous ethanol (to
help increase the solubility of the haloalkane). The mixture is heated under
reflux.
This mechanism forms a true intermediate carbocation , as the cation itself is
relatively stable. Although this happens, this step is very slow and so is
regarded as the part of the reaction that determines the reaction rate.
HO
-
H3C
CH3
CH3
HO
Br
CH3
Br
-
+
-
C
CH3
H3C
Once the carbocation has formed it will quickly react with the attacking
nucleophile, as its electrons will be highly attracted to the carbocation itself.
The carbocation is planar, which suggests that the substitution of the
nucleophile could happen on either side. In reality there is some steric
hindrance from the departing bromide ion and so the hydroxide slightly
favours the opposite side.
CH3
HO
-
H3C
Br
CH3
-
+
Br
C
HO
-
CH3
CH3
CH3
Effectively the hydroxide ion has taken the place of the leaving bromide ion.
Because the slow first step of this mechanism only involves one species (the
haloalkane) this is an S N 1 reaction, where S stands for substitution and N
refers to nucleophilic. The ‘1’ also means it is a first-order reaction (see the
unit on physical chemistry).
CH3
CH3
HO
-
H3C
Br
CH3
HO
-
CH3
-
Br
-
+
Br
C
H3C
HO
CH3
In general, if the compound (the haloalkane in this case) can form a relatively
stable positive ion (cation) then the more favourable reaction will be via the
S N 1 mechanism. Other compounds will react via the S N 2 mechanism. The
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CH3
CH3
ORGANIC SYNTHESIS NOTATION
more heavily substituted the cations are, the more stable they will be. In the
case of haloalkanes, tertiary and some secondary haloalkanes react via the
S N 1 mechanism, as the attacking nucleophile would have to negotiate its way
to the carbon atom between the sometimes large alkyl groups . The reaction is
much less likely to proceed via the S N 2 reaction mechanism (see below).
S N 2 reaction mechanisms
In an S N 2 mechanism there are two species involved in the rate-determining
step. This type of mechanism is more likely to occur with a prima ry
haloalkane, such as bromoethane, as used here.
CH3
-
Br
-
: Br
-
-
H
CH3
CH3
HO
Br
HO
H
H
HO
H
H
H
This is a one-step reaction in which a single five-centred transition state is
formed. The hydroxyl group approaches from the side away from the
bromine. In this reaction the S stands for substitution, N for nucleophilic and
the 2 is because the initial stage of the reaction involves two species – the
bromoethane and the hydroxide ion. The ‘2’ also means it is a second-order
reaction (see the unit on physical chemistry).
By using a chiral haloalkane the final product is one where the configuration
of the carbon atoms has inverted.
-
CH3
-
H5C2
Cl
CH3
CH3
HO
Cl
HO
H
H5C2
:Cl
-
HO
H
C2H5
H
This is called the Walden inversion, since it was first observed in 1896 by
chemist Paul Walden. In the Walden cycle it is possible to convert one
enantiomer of a chemical compound into the other enantiomer and back
again.
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