Pharmaceutical Organic Chemistry III

Pyridine is a nitrogen-containing heterocyclic compound essential in pharmaceuticals, agrochemicals, and organic synthesis. Chemical Formula of Pyridine: C₅H₅N Physical Properties of Pyridine: Property Value Appearance Colorless liquid Odor Fish-like, unpleasant Boiling Point ~115 °C Melting Point ~-41 °C Solubility Miscible with water and organics Basicity (pKa of conjugate acid) ~5.2 (moderately basic) Medicinal Uses: Pyridine … Read more

Reactions of Thiazole include electrophilic substitution, metalation, oxidation, and reduction pathways significant in medicinal chemistry. Reactions of Thiazole Electrophilic Aromatic Substitution (EAS) Like oxazole, C-5 is the most reactive site. Easier than oxazole due to lower electronegativity of sulfur. Examples: Bromination: Thiazole + Br₂ → 5-bromothiazole Nitration: HNO₃/H₂SO₄ → 5-nitrothiazole Friedel–Crafts acylation: Rare, can occur … Read more

Synthesis of Thiazole explains key routes like Hantzsch, Gabriel, and cyclization strategies with reagents, mechanisms, and applications. Hantzsch Thiazole Synthesis (Classical and widely used) Reactants: α-haloketone + thioamide Conditions: Reflux in ethanol or basic medium Reaction: CH₃COCH₂Cl + NH₂–CS–NH₂ → Thiazole derivative Mechanism: Nucleophilic attack by thioamide Cyclization Elimination of HCl Gabriel Synthesis Uses α-haloketone … Read more

Thiazole is a sulfur and nitrogen heterocyclic ring important in drug design, vitamins, and medicinal chemistry. Chemical Formula of Thiazole: C₃H₃NS Physical Properties of Thiazole: Property Value Appearance Colorless to pale yellow liquid Boiling Point ~116 °C Melting Point ~-30 °C Solubility Soluble in organic solvents Basicity Weakly basic Medicinal Uses: Found in many biologically … Read more

Oxazole is a five-membered aromatic heterocyclic compound containing one oxygen and one nitrogen atom, important in pharmaceuticals. Chemical Formula of Oxazole: C₃H₃NO Physical Properties: Property Value Appearance Colorless liquid Boiling Point ~69–70 °C Melting Point ~-2 °C Solubility Soluble in organic solvents Basicity Weakly basic Medicinal Uses of Oxazole: Used as a bioisostere of oxadiazoles … Read more

Reactions of Imidazole include electrophilic substitution at C-4/C-5 and nucleophilic substitution at C-2. Reactions of Imidazole Tautomerism: Prototropic tautomerism: 1H-imidazole  ⇌  3H-imidazole In practice, 1H-tautomer is more stable and dominates. Electrophilic Substitution Reactions (EAS): EAS occurs readily at position-4 or 5 due to high electron density. Nitration: Milder conditions than for benzene. Forms 4- or … Read more

Synthesis of Imidazole includes Debus synthesis and Radiszewski method using glyoxal, aldehyde, and ammonia. Synthesis of Imidazole Debus–Radziszewski Synthesis (most commonly used) Reactants: Aldehyde (e.g., formaldehyde) 1,2-dicarbonyl compound (e.g., glyoxal) Ammonia (or primary amines) Reaction: Glyoxal  +  NH₃  +  CH₂O  →  Imidazole  +  H₂O Mechanism: Schiff base formation Cyclization via nucleophilic attack Aromatization by dehydration … Read more

Reactions of Pyrazole mainly include electrophilic substitution at the 4-position and oxidation or reduction pathways. Reactions of Pyrazole Tautomerism: Pyrazole exhibits prototropic tautomerism between N-1 and N-2. 1H-pyrazole    ⇌    2H-pyrazole This affects reactivity at the nitrogen atoms and the electron density distribution on the ring. Electrophilic Substitution Reactions (EAS): Due to the electron-rich ring, EAS … Read more

Synthesis of Pyrazole involves methods like Knorr synthesis using 1,3-dicarbonyl compounds and hydrazines. Condensation of 1,3-Dicarbonyl Compounds with Hydrazine (most common method) Reactants: 1,3-diketones (e.g., acetylacetone) Hydrazine (NH₂NH₂) or substituted hydrazines Reaction: CH₃COCH₂COCH₃  +  NH₂NH₂  →  3,5-Dimethylpyrazole  +  H₂O Mechanism: Formation of hydrazone at one carbonyl Intramolecular cyclization Elimination of water → Pyrazole ring Advantages: … Read more