Unit – IV: Stereochemistry, Reaction Mechanism and synthesis of drug
molecules
Structural Representations of Organic Compounds
Structural formula (skeletal formula) refers to the illustration of a compound which
shows the arrangement of the atoms inside it.
Structural formulas of normal butane
Skeletal formula of dichloroacetic acid
Wedge and Dash Representation Saw-Horse Projection
Structure of Methane staggered and eclipsed conformations of ethane
Isomers are compounds that have the same chemical formula, but the atoms in the compound are
arranged differently. Two isomers will therefore have different properties.
Configurational isomers
• Chiral compound – a compound that is optically active (achiral compound will not
rotate light). An object without symmetry is CHIRAL
Enantiomers - Nonsuperposable mirror images, or chiral molecules which are mirror
images
Diastereomers - Stereoisomers which are not enantiomers (or mirror images).
Optical activity - The ability of chiral substances to rotate the plane of polarized light by
a specific angle.
Dextrorotatory - Ability of chiral substances to rotate the plane of polarized light to the
right.
Levorotatory - Ability of chiral substances to rotate the plane of polarized light to the left.
Specific rotation - The measured angle of rotation of polarized light by a pure chiral
sample under specified standard conditions (refer to textbook for a description of these).
Racemic mixture, racemic modification, or racemate - A mixture consisting of equal
amounts of enantiomers. A racemic mixture exhibits no optical activity because the
activities of the individual enantiomers are equal and opposite in value, therby canceling
each other out.
Absolute configuration: (Actual arrangement of substituents in space)
An absolute configuration refers to the spatial arrangement of the atoms of
a chiral molecular entity (or group) and its stereochemical description e.g. R or S,
referring to Rectus, or Sinister, respectively.
Conformation alanalysis of n- butane.
Nucleophilic substitution reactions :Nucleophilic substitution reactions occur when an
electron rich species, the nucleophile, reacts at an electrophilic saturated C atom attached
to an electronegative group (important), the leaving group; the positive or partially
positive atom is referred to as an electrophile. The whole molecular entity of which the
electrophile and the leaving group are part is usually called the substrate. The most
general form of the reaction may be given as the following:
Nuc: + R-LG → R-Nuc + LG:
Addition of HBr to propene. Markownikoff and anti Markownikoff’s additions.
The main difference between Markovnikov and Anti Markovnikov rule is that Markovnikov rule
indicates that hydrogen atoms in an addition reaction are attached to the carbon atom with more
hydrogen substituents whereas Anti Markovnikov rule indicates that hydrogen atoms are
attached to the carbon atom with the least hydrogen substituents.
Grignard additions on carbonyl compounds:
The Grignard reaction (pronounced /ɡriɲar/) is an organometallic chemical reaction in
which alkyl, vinyl, or aryl-magnesium halides(Grignard reagents) add to a carbonyl group in
an aldehyde or ketone. The Grignard reagent functions as a nucleophile, attacking
the electrophilic carbon atom that is present within the polar bond of a carbonyl group.
Elimination reactions:
Dehydro halogenation of alkylhalides.
Saytzeff rule.
Oxidation of alcohols using KMnO4
Oxidation is an important process and has played an important role in organic synthesis
Oxidation of alcohols with Potassium permanganate: Primary and secondary alcohols are readily
oxidized by permanganate ion both in acidic and basic medium
Oxidation of alcohols using Chromic acid
Reduction of carbonyl compounds using LiAlH4 &NaBH4.
Hydroboration of olefins.
Structure, synthesis and pharmaceutical applications of Paracetamol and Aspirin.
Paracetamol is used to treat many
conditions such as headache,
muscle aches, arthritis, backache,
toothaches, colds, and fevers.
Aspirin
Analgesic: Relieves pain without
anesthesia or loss of consciousness
Antipyretic: Reduces a fever
Anti-inflammatory: Lowers
inflammation when used in higher
SHORT ANSWER QUESTIONS doses
1. Differentiate Enantiomers & diastereomers.
2. What is a racemic mixture and how it can be resolved?
3. What conditions are present to determine whether a reaction will be Substitution or
elimination?
4. What is Markownikov’s rule? Justify the Markownikov’s addition of HBr to isobutylene.
5. Using a Grignard reagent of your own choosing (not necessarily CH3CH2MgBr), how
would you make a sample of the alcohol 2-methylpropan-2-ol?
6. Why NaBH4 is less reactive than LiAlH4?
OBJECTIVE ANSWER QUESTIONS
1. Stereoisomers that are exact mirror images of one another are called _____.
a. Diastereomers
b. Enantiomers
c. Constitutional isomers
d. Geometrical isomers
2. Which statement regarding stereoisomers is correct?
a. A stereoisomer of a drug typically has the same effect and potency as
the original.
b. Most biological molecules have at least one stereoisomer.
c. A pair of stereoisomers can easily convert between the two structures.
d. All statements are correct.
3. Hexane and 3-methylpentane are examples of:
a. enantiomers.
b. stereoisomers.
c. diastereomers.
d. constitutional isomers.
4. (2R,4S) –2,4–Dichloropentane and (2S,4R)-2,4-dichloropentane are:
a. enantiomers
b. diastereomers
c. identical
d. conformational isomers
e. constitutional isomers
5. Which of the following molecules is achiral?
a. (2R,3R)-2,3-Dichloropentane
b. (2R,3S)-2,3-Dichloropentane
c. (2S,4S)-2,4-Dichloropentane
d. (2S,4R)-2,4-Dichloropentane
e. Two of these
Fill in the blanks
1) N-acetyl-para-aminophenol is the chemical name of _________
2) The infinity of intermediate conformations are called __________
3) Conversion of an aldehyde to an alcohol is known as _________
4) The products of the reaction of a carboxylic acid and an alcohol would be_______
5) Molecules which are not superposable on their mirror images are called _________
6) ___________reaction at a saturated carbon is concerted.
7) Secondary alcohols on oxidation always produces __________
8) LiAlH4 and NaBH4 are both capable of __________ aldehydes and ketones to the
corresponding alcohol.
9) __________ & __________ are the precursors of aspirin.
10) ___________Rule implies that base-induced eliminations (E2) will lead predominantly to
the olefin in which the double bond is more highly substituted
