CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
COURSE OUTLINE: PRELIMS
1.
2.
3.
4.
5.
6.
Introduction to Organic Chemistry
Acids & Base
Introduction to Organic Molecules and Functional
Groups
Physical & Chemical Properties
Isomerism
Aliphatic Hydrocarbons
● E & Z Configuration of Alkenes
INTRODUCTION TO ORGANIC
CHEMISTRY
ORIGIN OF ORGANIC CHEMISTRY
-
Foundations date from mid-1700’s
Compounds obtained from plants and animals
Low-melting solids
Hard to isolate, purify and work with
Organic compounds were considered to have some vital
force as they were from living sources.
Thought that it could not be synthesized in
laboratory.
Organic Compound
●
●
●
●
●
●
●
Bonding is almost entirely
covalent.
May be gases, liquids or
solid with low melting points
(less than 360°C).
Most are insoluble in water.
Most are soluble in organic
solvents such as diethyl
ether, toluene, and
dichloromethane.
Aqueous solutions do not
conduct electricity.
Almost all burn.
Reactions are usually slow.
Inorganic Compounds
●
●
●
●
●
●
●
Most have ionic
bonds.
Most are solids
with high melting
points.
Many are soluble
in water.
Almost all are
insoluble in
organic solvents.
Aqueous
solutions conduct
electricity.
Very few burn.
Reactions are
often fast.
Carbon is a Group 4A element.
● Can share 4 valence electrons and form 4 covalent
bonds.
● Able to bond with one another to form long chains
and rings.
● Only element that has the ability to form immense
diversity of compounds.
1816, Chevreul found that soap can be separated into
several organic compounds which he termed fatty acids.
1828, Wohler showed that it was possible to convert
inorganic salt ammonium cyanate into organic substance
urea.
Organic Chemistry is the study of carbon compounds. More
than 50 million known chemical compounds contain carbon.
1 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
STRUCTURE AND BONDING
THE ENERGY LEVEL
Atom is consist of:
● Nucleus = proton + neutron
● Electron
Nucleus:
● Contains essentially all the mass of the atom.
Diameter of an atom is about 2x10-10m.
● 200 picometers (pm) [the unit ångström (A) is
10-10m = 100 pm)
ATOMIC
STRUCTURE:
CONFIGURATION
ELECTRON
Ground-state electron configuration:
● Listing of orbitals occupied by an atom’s electrons
● Called lowest - energy arrangement
Rules
●
Atomic number (Z) - number of protons or electrons in an
atom’s nucleus
Mass number (A) - number of protons plus neutrons
Atomic mass or atomic weight - weighted average mass in
atomic mass units (amu) of an element’s naturally occurring
isotope
Isotopes - atoms with the same atomic number but different
mass numbers
ATOMIC STRUCTURE - ORBITALS
Wave equation - mathematical equation that describes the
behavior of a specific electron in an atom
● Wave function, or orbital, is the solution of the wave
equation
● Denoted by the Greek letter psi (Ψ)
4 Kinds of Orbitals:
● S orbitals - Spherical, nucleus at the center
● P orbitals - Dumbbell–shaped, nucleus at the
middle (px py or pz)
○ Node - Region of zero electron density
● D orbitals - Elongated dumbbell-shaped, nucleus at
the center
● F orbital
-
Lowest-energy orbitals fill first in the order of 1s 2s
2p 3s 3p 4s 3d Aufbau principle.
Pauli exclusion principle
● Electrons act as if they were spinning around an
axis.
● Spin can have only two orientations, up and down.
● Only two electrons can occupy an orbital, and they
must be of opposite spin.
Hund’s rule
● If two or more empty orbitals of equal energy are
available, electrons occupy each with parallel spins
until all orbitals have one electron.
CHEMICAL BONDING
In 1858, August Kekule and Archibald Couper independently
proposed that, in all organic compounds, carbon is
tetravalent. This means that it always forms four bonds when
it joins other elements.
In 1874, Jacobus van’t Hoff and Joseph Le Bel proposed that
the four bonds of Carbon are not oriented randomly but have
specific directions.
Orbitals in an atom are organized into different
electron shells.
Centered around the nucleus in shells of increasing
size and energy.
Different shells contain different numbers and kinds
of orbitals.
Each orbital can be occupied by two electrons.
1.
Draw a molecule of chloromethane, CH3Cl, using
solid, wedged, and dashed lines to show its
tetrahedral geometry.
2 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
DEVELOPMENT OF CHEMICAL BONDING THEORY
Atoms form bonds because the resulting compound is more
stable than the separate atoms.
Valence shell - atom’s outermost shell
Ionic bonds - ions held together by a electrostatic attraction
formed as a result of electron transfers
Covalent bond - formed by sharing of electrons e.g CH4,
methane
●
●
●
Organic compounds have covalent bonds from
sharing electrons.
Electron-dot structure (Lewis structure):
○ Represents valence shell electrons of an
atom as dots
Line-bond structure (Kekulé structures):
○ Indicates two-electron covalent bond as a
line drawn between atoms
FORMING COVALENT BONDS: VALENCE BOND
THEORY
According to this theory, a covalent bond forms when two
atoms approach each other closely and a singly occupied
orbital on one atom overlaps a singly occupied orbital on the
other atom.
● H—H bond results from the overlap of two singly
occupied hydrogen 1s orbitals
● H—H bond is cylindrically symmetrical, sigma (σ)
bond
Reaction 2 H Ⓡ H2 releases 435 kJ/mol
H—H has a bond strength of 436 kJ.mol (1 kJ - 0.2390 kcal;
1 kcal - .184 kJ)
Bond length: Ideal distance between nuclei that leads to
maximum stability
● If too close, they repel
● If too far apart, bonding is weak
● The distance of H—H is 74 pm
Number of covalent bonds an atom forms depends on the
number of additional valence electrons it needs to reach a
stable octet.
●
●
Carbon has four valence electrons (2s2 2p2),
forming four bonds
Nitrogen has five valence electrons (2s2 2p3),
forming three bonds
CARBON HYBRIDIZATION
●
Lone pair - valence electrons not used in bonding
Example:
Nitrogen atom in ammonia (NH3)
● Shares six valence electrons in three covalent
bonds
● Two valence electrons are nonbonding lone pair
●
Hybridization occurs when atoms are ready to
form bonds.
○ To predict the bond angles in these
molecules we use the Valence-Shell
Electron-Pair (VSEPR) Model
Bond angle - the angle between atoms bonded to a
central atom.
3 Hybrid Orbitals:
● sp3
● sp2
● sp
3 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
sp3 - HYBRID ORBITAL AND STRUCTURE OF
METHANE (CH4)
●
●
●
●
Proposed by Linus Pauling
S orbital and three p orbital can combine, or
hybridize, to form four equivalent atomic orbitals
with tetrahedral orientation.
109.5° angle
Has SINGLE BOND
E.g. Methane
● Each C—H bond has a strength of 439 kJ/mol and
a length of 109 pm
● Angle formed is 109.5° (tetrahedral angle)
● Bond angle: Formed between two adjacent bonds
sp2 - HYBRID ORBITALS
●
●
●
●
●
●
sp2 orbitals are in a plane with an angle of 120°
from each other.
Exhibits double bond
Trignal
Planar geometry
Head-on overlap gives what is called a sigma (σ)
bond.
Sideways overlap gives a pi (π) bond.
E.g. Ethylene (C2H4)
● H atoms forms bonds with four sp2 orbitals
● H—C—H and H—C—C form bond angles of about
120°
● C—C double bond in ethylene is shorter and
stronger than single bond in ethane.
sp3 - HYBRID ORBITAL AND STRUCTURE OF
METHANE (C2H6)
●
The simplest molecule containing a carbon-carbon
bond.
●
●
C—H bond is a bit weaker, 439 kJ/mol
C—C bond is 154 pm long
sp - HYBRID ORBITALS
●
●
Carbon can form a triple bond sharing six elements.
Carbon 2s orbital hybridizes with a single p orbital
giving two sp hybrids sp orbitals are linear
geometry, 180° apart on x-axis.
E.g. Acetylene (C2H2)
● Sharing of six electrons forms C°C
● Two sp orbitals form s bonds with hydrogens.
● Shortest and strongest carbon—carbon bond
4 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
HYBRIDIZATION
OF
NITROGEN,
PHOSPHORUS, AND SULFUR
OXYGEN,
RULES FOR DRAWING SKELETAL
Structures:
● Carbon atoms aren’t usually shown.
● Carbon atom is assumed to be at each intersection
of two lines (bonds) and at the end of each line.
● Hydrogen atoms bonded to carbon aren’t shown.
● Atoms other than carbon and hydrogen are shown.
MOLECULAR ORBITAL (MO) THEORY
ELECTRONEGATIVITY
Description of covalent bond formation as resulting from a
mathematical combination of atomic orbitals to form
molecular orbitals.
Polar covalent bonds - bonds that are neither fully ionic nor
fully covalent but are somewhere between the two extremes.
Electronegativity - intrinsic ability of an atom to attract the
shared electrons in a covalent bond.
●
●
Bonding MO - molecular orbital that is lower in
energy than the atomic orbitals from which it is
formed.
Antibonding MO - molecular orbital that is higher in
energy than the atomic orbitals from which it is
formed.
Differences in EN produce bond polarity F is most
electronegative (EN = 4.0), Cs is least (EN = 0.7).
DRAWING OF CHEMICAL STRUCTURES
Condensed structures: C—H or C—C single bonds are not
shown, they are understood.
5 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
SOLVING OF FORMAL CHARGE
RESONANCE HYBRIDS
Formal Charges - a device for electron bookkeeping
Example:
Calculate formal charges on the four O atoms in the
methyl phosphate dianion.
Structure with resonance forms, that does not alternate
between the forms.
Example - Benzene (C6H6) has two resonance forms with
alternating double and single bonds.
● Is a hybrid of the two individual forms.
● All six carbons — carbon bonds are equivalent.
Solution:
RULES FOR RESONANCE FORMS
Individual resonance forms are imaginary.
● Real structure is a hybrid of different forms.
Resonance forms differ only in the placement of their p or
nonbonding electrons.
● Curved arrow indicates the movement of electrons,
not of the atoms.
RESONANCE
Some molecules have structures that cannot be shown with
a single representation. Represented by structures that
contribute to the final structure but differ in the position of the
p bond or lone pair.
● Such structures are delocalized and are
represented by resonance forms.
STABILITY
OF
RESONANCE
ALLYLIC
CARBOCATIONS:
Allylic carbocation is stable because it is symmetrical. Allylic
carbocation has a single, unchanging structure called
resonance hybrid.
Resonance Forms - the two individual structures of an allylic
carbocation.
● Their special relationship is indicated by a double
headed arrow placed between them.
● The only difference between the resonance forms is
the position of bonding electrons.
● Atoms remain in the same place in both resonance
forms.
Just imagine a resonance hybrid as being like a mixed-breed
dog. A resonance hybrid doesn’t change back and forth
between forms. The greater the number of possible
resonance forms, the greater the stability.
6 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
ACIDS & BASE
RELATIVE STRENGTHS OF SOME COMMON
ACIDS AND THEIR CONJUGATE BASES
BRONSTED-LOWRY
Bronsted-Lowry acid is a substance that donates a
hydrogen ion (H+).
Bronsted-Lowry base is a substance that accepts a
hydrogen ion.
Conjugated acid
Conjugate base
ACIDITY CONSTANT (Ka)
There is an inverse relationship between the acid strength of
an acid and the base strength of its conjugate base. A strong
acid yields a weak conjugate base, and a weak acid yields a
strong conjugate base.
Remember from general chemistry that the concentration of
solvent is ignored in the equilibrium expression and that
brackets [ ] around a substance refer to the concentration of
the enclosed species in moles per liter.
●
●
Stronger acids have their equilibria toward the right
and thus have larger Ka.
Weaker acids have their equilibria toward the left
and have smaller acidity constants.
pKa
Acid strengths are normally given using pKa values rather
than Ka values, pKa is the negative common logarithm of the
Ka (-log Ka)
●
●
Stronger acid - larger Ka ; smaller pKa
Weaker acid - smaller Ka ; larger pKa
7 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
ORGANIC ACIDS AND ORGANIC BASES
Organic acids are characterized by the presence of a
positively polarized hydrogen atom
2 Main Kinds:
1. Contain a hydrogen atom bonded to an
electronegative oxygen atom (O-H)
● e.g Methanol and acetic acid
2. Contain a hydrogen atom bonded to a carbon atom
next to a C=O double bond (O=C-C-H)
● e.g Acetone
THE LEWIS DEFINITION
●
●
Lewis acid is a substance that accepts an electron
pair.
Lewis base is a substance that donates an electron
pair.
A curved arrow always means that a pair of electrons move
from the atom at the tail of the arrow to the atom at the head
of the arrow.
Organic bases are characterized by the presence of an
atom with a lone pair of electrons that can bond to H+
● E.g. Nitrogen-containing compounds such as
methylamine
Note: Methanol & Acetone can act as an acid when they
donate protons but act as bases when their O atom accepts
a proton.
8 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
INTRODUCTION TO ORGANIC
MOLECULES AND FUNCTIONAL
GROUPS
FUNCTIONAL GROUPS WITH CARBON SINGLY
BONDED TO AN ELECTRONEGATIVE ATOM
FUNCTIONAL GROUP
OVERVIEW OF FUNCTIONAL GROUP
A group of atoms within a molecule that has a characteristic
chemical behavior.
The chemistry of every organic molecule, regardless of size
and complexity, is determined by the functional groups it.
FUNCTIONAL GROUPS WITH CARBON—OXYGEN
DOUBLE BAND (CARBONYL GROUPS)
●
●
●
●
FUNCTIONAL GROUPS WITH CARBON—CARBON
MULTIPLE BANDS
●
●
Aldehydes have at least one hydrogen bonded to
the C=O
Ketones have two carbons bonded to the C=O
Carboxylic acids have one carbon and one OH
group bonded to the C=O
Esters have one carbon and one ether-like
oxygen bonded to the C=O
Amides have one carbon and one nitrogen
bonded to the C=O
Acid chlorides have one carbon and one chlorine
bonded to the C=O
9 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
●
The discovery of penicillin in 1928 marked the
beginning of what has been called the "golden age
of chemotherapy,” in which previously
life-threatening ] fe] bacterial infections were
transformed into little more than a source of
discomfort. For those who are allergic to penicillin, a
variety of antibiotics, including tetracycline, are
available.
Identify the numerous functional groups in the
tetracycline molecule.
●
Root beer hasn't tasted the same since the use of
sassafras oil as a food additive was outlawed
because sassafras oil is 80% safrole, which has
been shown to cause cancer in rats and mice.
Identify the functional groups in the structure of safrole.
●
Identify the functional groups in the antibiotic,
PENICILLIN.
The following compounds are the active ingredients
in over-the-counter drugs used as analgesics (to
relieve pain without decreasing sensibility or
consciousness), antipyretics (to reduce the body
temperature when it is elevated), and/or
anti-inflammatory agents (to counteract swelling or
inflammation of the joints, skin, and eyes).
Identify the functional groups in each molecule.
10 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
FUNCTIONAL GROUPS AND REACTIVITY
INTERNATIONAL UNION OF PURE AND APPLIED
CHEMISTRY (IUPAC) NOMENCLATURE
SAMPLE IUPAC NAMING
PHYSICAL AND CHEMICAL
PROPERTIES
PHYSICAL PROPERTIES
The physical properties of organic compounds fides both
quantitative and qualitative features.
INTRODUCTION TO NOMENCLATURE OF
ORGANIC COMPOUNDS
NOMENCLATURE
●
●
●
Other term for NAMING.
Isolated from URINE.
MORPHEUS, God of Dreams.
Quantitative: melting point, boiling point, and index of
refraction.
Qualitative: odor, consistency, solubility, and color.
Hydrocarbons like alkanes, cycloalkanes, and alkenes all
share similar physical properties.
● They only contain non-polar bonds
(London-dispersion intermolecular forces of
attraction).
● Insoluble in water
● Soluble in nonpolar
● Some slightly polar solvents.
● Nearly all alkanes have densities less than 1.0 g/mL
and are therefore less dense than water.
● The boiling points and melting point increase as
size increases because more energy is required to
separate them.
● Organic compounds typically melt and’‘many boils.
● This general trend for melting and boiling points
holds true for the straight-chain homologs of all
organic compound families.
○ The melting and boiling points correlate
with the polarity of the molecules and their
molecular weight.
11 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
CHEMICAL PROPERTIES
Kinds of Organic Reactions
1. Addition reactions: Two reactants combining to
form a single product.
2.
3.
Elimination reactions: Single reactant splitting into
two products.
STEPS REQUIRED FOR METHYL CHLORINATION
●
Initiation
●
Propagation
○ Reaction with molecule to generate radical
●
Termination
○ Combination of two radicals to form a
stable product
Substitution reactions: Two reactants exchanging
parts to form two new products.
POLAR REACTIONS
4.
Rearrangement reactions: Single reactant yielding
an isomeric product through reorganization of its
bonds and atoms
Mechanisms by which Most Reactions Take Place: Radical
and Polar
● Radical reactions: Processes that involve
symmetrical bond-breaking and bond-making.
● Radical: Neutral chemical species containing odd
number of electrons
○ Has a single, unpaired electron in one of
its orbitals
● Polar reactions: Processes involving
unsymmetrical bond-breaking and bond-making.
Polarizability: Tendency of atoms in a molecule to undergo
polarization
● Larger atoms, easily polarizable
● Smaller atoms, less polarizable
●
●
Nucleophile: Electron-rich species that donate
electron pairs to electrophile in a polar bond-forming
reaction
○ Is a Lewis base
Electrophile: Substances that accept electron pairs
from a nucleophile
○ Is a Lewis acid
RADICAL REACTIONS
●
●
Not as common in comparison to polar reactions.
Radicals react to complete electron octet of valence
shell.
A radical can add to an alkene to give a new radical, causing
an addition reaction.
12 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
An Example of a Polar Reaction: Addition of HBr to
Ethylene
● Electrophilic addition reaction
● π part results from p—p overlap
● σ results from sp2—sp2 overlap
● Double bond is more accessible to approaching
reactants than a single bond
○ More electron-rich
RULES FOR USING CURVED ARROWS
●
Electrons move from a nucleophilic source to an
electrophilic sink
●
The nucleophilic site can be neutral or negatively
charged
●
The electrophilic site can be neutral or positively
charged
A Comparison of Carbon—Carbon Single and Double
Bonds
DESCRIBING A REACTION: EQUILIBRIA, RATES,
AND ENERGY CHANGES
●
●
To reach equilibrium, reactions go in either forward
or reverse directions
The multiplied concentrations of the products
divided by the multiplied concentrations of the
reactant is the equilibrium constant, Keq.
○ Each concentration is raised to the power
of its coefficient in the balanced equation.
MECHANISM
●
●
Polar reactions occur by combination of an
electron-rich site of a nucleophile and an
electron-deficient site of an electrophile
Carbocation: Substance that contains a trivalent,
positively charged carbon atom having six electrons
in its outer shell
●
●
●
●
If value of Keq is > 1
○ Indicates that product concentration term
is larger than the reactant concentration
term.
○ Reaction takes place from left to right.
If Keq is 1
Quantity of reactant and product present at
equilibrium is large
If value of Keq is < 1
○ Reaction takes place in the reverse
direction
13 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
●
●
●
●
Gibbs free energy (AG): Change in energy that
occurs during a chemical reaction
○ ΔG = Gproducts - Greactants
○ Energy is released on the favored side of
an equilibrium reaction reactants
Exergonic: Reaction that has negative free energy
change and is therefore spontaneous
○ Energy is lost
Endergonic: Reaction that has positive free energy
change
Energy is absorbed
Standard free energy change at 1 atm pressure and 298 K is
denoted as ΔG°.
● Relationship between free energy change and an
equilibrium constant is:
● ΔG° = - RT in Keq
● Where,
○ R = 1.987 cal/(K - mol)
○ T = Temperature in Kelvin
○ In Keq = Natural logarithm of Keq
● Enthalpy change (AH): Measure of change in total
bonding energy during a reaction
○ Called heat of reaction
● Exothermic: Reaction that releases heat
● Endothermic: Reaction that absorbs heat
● Entropy change (ΔS): Measure of the change in
the amount of molecular randomness
● Keq tells the position of the equilibrium
○ Amount of product that is theoretically
possible
DESCRIBING A REACTION: BOND DISSOCIATION
ENERGIES
●
Bond dissociation energy (D): Amount of energy
required to break a given bond to produce two
radical fragments when the molecule is in the gas
phase at 25°C.
DESCRIBING A REACTION: ENERGY DIAGRAMS
AND TRANSITION STATES
●
●
●
●
●
●
Transition state: Highest energy point in a reaction
step
Activation energy, ΔG*: Energy required to go
from reactant to transition state
In the addition of HBr
Transition-state structure for the first step
○ π bond between the carbons begins to
break
■ C—H bond is partially formed
■ H—Br bond begins to break
Once the transition state is reached the reaction
may:
○ Continue to give the carbocation product
Revert back to reactants
Every reaction has its own energy profile
DESCRIBING A REACTION: INTERMEDIATES
●
●
If a reaction occurs in more than one step, it must
involve species that are neither the reactant nor the
final product.
○ Called reaction intermediate
Each step has its own free energy of activation
Energy is determined by the type of bond
● Changes in bonds can be used to calculate net
changes in heat
14 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
COMPARISON
BETWEEN
BIOLOGICAL
REACTIONS AND LABORATORY REACTIONS
●
●
●
Laboratory reactions are often carried out in an
organic solvent.
○ Often done using relatively simple
reagents
○ Catalyst might be used
Biological reactions occur in an aqueous medium
inside cells.
○ Involve relatively complex reagents called
coenzymes
○ Enzymes provide an alternative
mechanism that makes life possible
Active site: Pocket in an enzyme where a substrate
is bound and undergoes reaction
ISOMERISM
ISOMERS — STEREOCHEMISTRY AT
TETRAHEDRAL CENTERS
ENANTIOMERS AND TETRAHEDRAL CARBON
Enantiomers
● Molecules that are not the same as their mirror
image.
● Greek: Enatio meaning opposite.
○ A result of tetrahedral bonding to four
different substituents.
E.g. Lactic Acid (2-hydroxypropanoic acid)
● Have 4 different groups (-H, -OH, -CH3, and CO2H) bonded to the central carbon atom.
● Both are found in sour milk, but only the (+)
enantiomer occurs in muscle tissue.
15 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
THE
REASON
FOR
MOLECULES: CHIRALITY
Chiral
●
●
●
●
HANDEDNESS
IN
Another way to identify a chiral molecule is to look for the
presence of a plane of symmetry.
Greek cheir, meaning “hand”.
A molecule that is not identical to its mirror
image.
Molecules that do not have a plane of symmetry
and are not superimposable on their mirror
image.
Cause of chirality is the presence of a carbon
atom bonded to four different groups — e.g
Hand, Lactic acid.
Achiral: Molecules with a plane of symmetry that is the
same as its mirror image.
Example: A coffee mug
Chirality Center or Stereocenter
● Point in a molecule where 4 different groups are
attached to carbon; it is the cause of chirality.
OPTICAL ACTIVITY
The study of chirality originated in the early 19th century
during the investigations by Jean-Baptiste Biot in the early
19th century investiga nature of plane polarized light.
Rotation, in degrees, a
Levorotatory: Optically active substance that rotates the
plane of polarization of plane-polarized light in
counterclockwise direction.
Dextrorotatory: Optically active substance that rotates the
plane of polarization of plane-polarized light in clockwise
direction.
16 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
SEQUENCE
RULES
CONFIGURATION
FOR
SPECIFYING
Cahn-Ingold-Prelog rules
● Rule #1
○ Look at the four atoms directly attached to
the chirality center, and rank them
according to atomic number
○ Atom with highest atomic number has
highest ranking, and atom with lowest
atomic number has lowest ranking
●
●
★
DIASTEREOMERS
These are stereoisomers that are not mirror images E.g Your
hand and your friend’s hand look similar, but they aren't
identical and they aren't mirror images.
#2 If a decision cannot be reached by ranking the
first atoms in the substituent, look at the second,
third, or fourth atoms until the difference is found.
#3 Multiple-bonded atoms are equivalent to the
same number of single-bonded atoms.
If the ranking (1 - 2 -3):
○ R configuration: Configuration of chirality
center if the curved arrow is drawn
clockwise
○ S configuration: Configuration of chirality
center if the curved arrow is drawn
counterclockwise
○ Absolute configuration: Exact 3-D
structure of a chiral molecule
Look at (-) lactic acid for an example of how to assign R and
S configuration.
RACEMATES
●
●
Racemates - are 50:50 mixtures of (+) and (-)
enantiomers.
Racemic Mixtures
○ Often denoted by the symbol (+/-) or by
the prefix d, l to indicate that they contain
equal amounts of dextrorotatory and
levorotatory enantiomers.
○ Show no optical activity.
17 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
ISOMERISM
STEREOISOMERS
Same connections, different spatial arrangement of
atoms
● Enantiomers (nonsuperimposable mirror images)
● Diastereomers (all other stereoisomers)
○ Includes cis, trans, and configurational
CONSTITUTIONAL ISOMERS
Compounds that have the same molecular formula and
different connectivity.
If both molecules have the same count for all of the different
atoms, and the atoms are arranged in different ways (their
connectivity is different), the molecules will be constitutional
isomers.
18 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
ALIPHATIC HYDROCARBONS
HYDROCARBONS (HC)
●
●
Composed of only two elements: carbon and
hydrogen.
Two types:
○ Aliphatic hydrocarbons
○ Aromatic hydrocarbons or Arenes.
ALIPHATIC & ALICYCLIC HYDROCARBONS
Aliphatic hydrocarbons are hydrocarbons based on chains
of C atoms.
a. Alkanes with only single covalent bonds.
b. Alkenes contain at least one C—C double bond.
c. Alkynes contain a C-C triple bond.
Aliphatic (from Greek aleiphar, “fat’”) described
hydrocarbons derived by chemical degradation of fats or oils.
Alicyclic hydrocarbons are those compounds which
contain rings of 3 or more carbon atoms which resemble
aliphatic (acyclic) hydrocarbons in their properties.
Classified into:
a. Cycloalkanes
b. Cycloalkenes
c. Cycloalkynes
PHYSICOCHEMICAL PROPERTIES OF ALIPHATIC
HC
●
●
●
Most aliphatic hydrocarbons are highly flammable
and readily react with oxygen in combustion
reactions.
Liquid aliphatic hydrocarbons have high vapor
pressure.
Nonpolar aliphatic hydrocarbons are compounds
that have equal charge distribution across the
molecule.
PHARMACEUTICAL USES OF HYDROCARBONS
Hydrocarbons are the principal constituents of petroleum and
natural gas. They serve as fuels and lubricants as well as
raw materials for the production of plastics, fibres, rubbers,
solvents, explosives, and industrial chemicals.
Many hydrocarbons occur in nature. In addition to making up
fossil fuels, they are present in trees and plants, as, for
example, in the form of pigments called carotenes that occur
in carrots and green leaves. More than 98 percent of natural
crude rubber is a hydrocarbon polymer, a chainlike molecule
consisting of many units linked together.
a.
Alkanes are aliphatic hydrocarbons with only single
covalent bonds. The smallest alkane is methane.
Physical Properties:
● Alkanes and cycloalkanes are nonpolar
substances.
● Attractive forces between alkane
molecules are dictated by London forces
and are weak.
● Have low boiling points compared with
polar molecules of comparable molecular
weight.
● Boiling points of alkanes increase with
increasing number of carbons.
Chemical Properties:
● Burn in air to produce carbon dioxide (CO,)
and water (H,O) and release heat.
Pharmaceutical Uses:
● Alkanes are very versatile and are being
used as solvents, heating oils, fuels, in fat
synthesis, in the synthesis of fatty acids by
air oxidation, in the manufacture of
albumen, in the transformation to olefins.
The ultimate condensed formula is-a line-angle formula
(line drawing/skeletal structure), in which carbon atoms
are implied at the corners and ends of lines, and each
carbon atom is understood to be attached to enough
hydrogen atoms to give each carbon atom four bonds.
19 I ADELANTAR, F.N
CENTRAL PHILIPPINE UNIVERSITY
COLLEGE OF PHARMACY 1ST YEAR - D
PHARMACEUTICAL ORGANIC CHEMISTRY - LECTURE
INSTRUCTOR DAREEN JOY B. TAYTAYON, RPH
POWERPOINT/LECTURE
NAMING (IUPAC NOMENCLATURE) - ALKANES
1.
2.
3.
4.
5.
Find and name the longest continuous carbon
chain.
Identify and name groups attached to this chain.
Number the chain consecutively, starting at the end
nearest a substituent group.
Designate the location of each substituent group by
an appropriate number and name.
Assemble the name, listing groups in alphabetical
order using the full name (e.g. cyclopropyl before
isobutyl).
The prefixes di, tri, tetra etc., used to designate several
groups of the same kind, are not considered when
alphabetizing.
NOTE: The IUPAC Systematic Approach to Nomenclature
●
●
●
A root or base indicating a major chain or ring of
carbon atoms found in the molecular structure.
A suffix or other element(s) designating functional
groups that may be present in the compound.
Names of substituent groups, other than hydrogen,
that complete the molecular structure.
Halogen substituents are easily accommodated, using the
names: fluoro (F-), chloro (CI-), bromo (Br-) and iodo (I-).
Practice: Name this molecule.
20 I ADELANTAR, F.N