Pharmaceutical Organic Chemistry I — B.Pharmacy 2nd Semester
Pharmaceutical Organic Chemistry I introduces the fundamentals of organic chemistry, including nomenclature, stereochemistry, and the chemistry of aliphatic and aromatic hydrocarbons. Understanding organic chemistry is essential for medicinal chemistry and drug design.
Unit 1: General Principles
Hybridization
Carbon exhibits three types of hybridization that determine molecular geometry:
- sp³: Tetrahedral geometry (109.5°) — saturated carbon (alkanes)
- sp²: Trigonal planar geometry (120°) — double bonds (alkenes)
- sp: Linear geometry (180°) — triple bonds (alkynes)
Bond Breaking
- Homolytic cleavage: Bond breaks symmetrically, each atom gets one electron → free radicals
- Heterolytic cleavage: Bond breaks asymmetrically, one atom gets both electrons → ions (carbocations, carbanions)
Types of Reagents
- Electrophiles: Electron-poor species (H⁺, NO₂⁺, BF₃, AlCl₃) — seek electron-rich sites
- Nucleophiles: Electron-rich species (OH⁻, CN⁻, NH₃, ROH) — seek electron-poor sites
Unit 2: Stereochemistry
Stereochemistry studies the three-dimensional arrangement of atoms in molecules. It is critical in pharmacy because enantiomers of drugs can have different pharmacological activities.
Types of Isomerism
- Constitutional (Structural) isomers: Same molecular formula, different connectivity
- Stereoisomers: Same connectivity, different spatial arrangement
- Enantiomers: Non-superimposable mirror images
- Diastereomers: Stereoisomers that are not mirror images
- Geometric (cis/trans) isomers: Restricted rotation around double bonds or rings
Optical Activity
Chiral molecules rotate the plane of polarized light. The (+) or dextrorotatory form rotates light clockwise; the (-) or levorotatory form rotates it counterclockwise. A racemic mixture (50:50) shows no net rotation.
Unit 3: Alkanes, Alkenes, and Alkynes
Alkanes (CₙH₂ₙ₊₂)
Saturated hydrocarbons with only C-C single bonds. Relatively unreactive. Key reactions: combustion, halogenation (free radical mechanism).
Alkenes (CₙH₂ₙ)
Unsaturated hydrocarbons with C=C double bonds. More reactive than alkanes due to the π bond. Key reactions: electrophilic addition (HBr, H₂O, Br₂), Markovnikov’s rule, anti-Markovnikov addition.
Alkynes (CₙH₂ₙ₋₂)
Unsaturated hydrocarbons with C≡C triple bonds. Terminal alkynes are weakly acidic (sp carbon). Key reactions: addition of H₂, HX, X₂, hydration.
Unit 4: Aromatic Chemistry
Aromatic compounds contain a planar ring of continuously overlapping p-orbitals with (4n+2)π electrons (Hückel’s rule). Benzene is the parent aromatic compound.
Electrophilic Aromatic Substitution (EAS)
The characteristic reaction of aromatic compounds. Common EAS reactions:
- Nitration: HNO₃/H₂SO₄ → introduces -NO₂
- Halogenation: X₂/Lewis acid → introduces -X
- Sulfonation: Fuming H₂SO₄ → introduces -SO₃H
- Friedel-Crafts Alkylation: RX/AlCl₃ → introduces -R
- Friedel-Crafts Acylation: RCOCl/AlCl₃ → introduces -COR
Unit 5: Alcohols and Phenols
Classification of Alcohols
- Primary (1°): -OH attached to carbon with one alkyl group
- Secondary (2°): -OH attached to carbon with two alkyl groups
- Tertiary (3°): -OH attached to carbon with three alkyl groups
Reactions of Alcohols
Oxidation, dehydration, ester formation, ether formation. Primary alcohols oxidize to aldehydes then carboxylic acids; secondary alcohols oxidize to ketones; tertiary alcohols resist oxidation.
Important Exam Questions
- Explain sp, sp², and sp³ hybridization with examples
- Define chirality and differentiate between enantiomers and diastereomers
- Explain Markovnikov’s rule with examples
- Describe the mechanism of electrophilic aromatic substitution
- Classify alcohols and explain their oxidation reactions
- What is aromaticity? Explain Hückel’s rule