Essential Organic Reactions and Stereochemistry Principles
Claisen-Schmidt Reaction
Introduction: The Claisen-Schmidt reaction is a crossed aldol condensation between an aromatic aldehyde and an aldehyde or ketone containing α-hydrogen in the presence of a base to form α,β-unsaturated carbonyl compounds.
Reagents
- Aromatic Aldehyde
- Aldehyde or Ketone containing α-hydrogen
- Sodium Hydroxide (NaOH) or Potassium Hydroxide (KOH)
Mechanism
- Formation of enolate ion from ketone.
- Nucleophilic attack on aldehyde carbonyl carbon.
- Formation of β-hydroxy carbonyl compound.
- Dehydration gives α,β-unsaturated carbonyl compound.
Schmidt Reaction
Introduction: The Schmidt reaction is an important rearrangement in which carboxylic acids, aldehydes, or ketones react with hydrazoic acid (HN₃) in the presence of concentrated sulphuric acid to form amines or amides with the evolution of nitrogen gas.
Mechanism
- Formation of acyl azide.
- Rearrangement with migration of alkyl or aryl group.
- Loss of nitrogen gas.
- Hydrolysis to form amine.
Oppenauer Oxidation
Introduction: Oppenauer oxidation is a selective oxidation reaction in which secondary alcohols are oxidized to ketones using aluminium alkoxides in the presence of a ketone such as acetone. It is the reverse of the Meerwein-Ponndorf-Verley (MPV) reduction.
Beckmann Rearrangement
Introduction: The Beckmann rearrangement is an important organic reaction in which oximes are converted into amides in the presence of acidic dehydrating agents. It involves the migration of a group from carbon to nitrogen with the simultaneous loss of water.
Clemmensen Reduction
Introduction: Clemmensen reduction is used for the reduction of aldehydes and ketones into corresponding hydrocarbons. The carbonyl group (>C=O) is completely reduced to a methylene group (-CH₂-).
Dakin Reaction
Introduction: The Dakin reaction is the oxidation of ortho or para hydroxy (or amino) substituted aromatic aldehydes and ketones using hydrogen peroxide in an alkaline medium to form phenolic compounds.
Birch Reduction
Introduction: Birch reduction is the partial reduction of aromatic compounds to form cyclohexadienes using sodium or lithium metal in liquid ammonia and alcohol.
Wolff-Kishner Reduction
Introduction: The Wolff-Kishner reduction converts aldehydes and ketones into hydrocarbons by reducing the carbonyl group (C=O) into a methylene group (CH₂).
Metal Hydride Reactions
Introduction: Metal hydrides, such as Lithium Aluminium Hydride (LiAlH₄) and Sodium Borohydride (NaBH₄), are essential reducing agents that donate hydride ions (H⁻) to reduce organic compounds.
Key Differences
- LiAlH₄ is a strong reducing agent; NaBH₄ is mild.
- LiAlH₄ reduces aldehydes, ketones, esters, acids, and amides; NaBH₄ mainly reduces aldehydes and ketones.
- LiAlH₄ reacts with water; NaBH₄ is stable in water.
Heterocyclic Compounds
Pyrimidine, Purine, and Thiazole
- Pyrimidine: A six-membered aromatic heterocyclic compound with two nitrogen atoms at positions 1 and 3.
- Purine: A fused heterocyclic compound consisting of a pyrimidine ring fused with an imidazole ring.
- Thiazole: A five-membered aromatic heterocyclic compound containing one sulphur and one nitrogen atom.
Pyridine and Imidazole
Pyridine: A six-membered aromatic heterocyclic compound. It is basic because the nitrogen lone pair is available for protonation.
Imidazole: A five-membered aromatic heterocyclic compound with two nitrogen atoms at positions 1 and 3.
Pyrrole, Furan, and Thiophene
These are five-membered aromatic heterocycles. Pyrrole contains nitrogen, Furan contains oxygen, and Thiophene contains sulphur. Their aromaticity is derived from the participation of the heteroatom’s lone pair in the π-electron system.
Stereochemistry
Stereospecific vs. Stereoselective
- Stereospecific: The stereochemistry of the reactant determines the stereochemistry of the product.
- Stereoselective: One stereoisomeric product is formed preferentially over another.
Conformations of Cyclohexane
The chair conformation is the most stable due to the absence of angle strain and torsional strain, with bond angles close to 109.5°.
Atropisomerism
Atropisomerism arises from restricted rotation about a single bond, often due to bulky substituents, allowing for the isolation of stable stereoisomers.
Geometrical Isomerism
Arises from restricted rotation around a double bond. Nomenclature uses cis/trans or the E/Z system based on Cahn-Ingold-Prelog priority rules.
Enantiomers, Diastereoisomers, and Meso Compounds
- Enantiomers: Non-superimposable mirror images.
- Diastereoisomers: Stereoisomers that are not mirror images.
- Meso Compound: Optically inactive due to an internal plane of symmetry despite having chiral centers.
Asymmetric Synthesis
- Partial: One enantiomer predominates due to chiral influence.
- Absolute: One enantiomer is formed from achiral reactants without chiral reagents.
Resolution of Racemic Mixtures
Methods include mechanical separation, preferential crystallization, chemical conversion to diastereomers, and biochemical resolution.
Optical Activity and Nomenclature
Optical activity is the rotation of plane-polarized light. The D/L system is based on glyceraldehyde configuration, while the R/S system uses Cahn-Ingold-Prelog priority rules to define absolute configuration.