Top 25 - Chemical rections in API synthesis

Top 25 chemical reactions along with brief definitions, mechanism overviews, and examples of their applications in pharmaceutical synthesis:

                                                1. Hydrogenation:
The addition of hydrogen to a compound, typically using a metal catalyst.
 Mechanism: Hydrogen molecules adsorb onto the catalyst surface, undergo homolytic cleavage, and the resulting hydrogen atoms add to the unsaturated bonds.
 Application: Reduction of alkenes to alkanes in the synthesis of pharmaceutical intermediates.

                                               2. Esterification:
Formation of an ester from a carboxylic acid and an alcohol, typically catalyzed by an acid.
Mechanism: Protonation of the carboxylic acid, nucleophilic attack by the alcohol, and deprotonation to form the ester.
Application: Synthesis of prodrugs in pharmaceutical chemistry.

                                               3. Grignard Reaction:
Formation of a carbon-carbon bond by the reaction of an organomagnesium halide with a carbonyl compound.
Mechanism: Nucleophilic addition of the Grignard reagent to the carbonyl carbon followed by proton transfer.
Application: Key step in the synthesis of complex pharmaceutical molecules like natural products and antibiotics.

                                              4. Acylation:
Introduction of an acyl group into a molecule, often via an acyl chloride or anhydride.
Mechanism: Nucleophilic attack of the carbonyl oxygen on the electrophilic acyl group.
Application: Formation of amides, an important functional group in pharmaceuticals, through amidation reactions.

                                           5. Friedel-Crafts Acylation:
Acylation of aromatic rings using an acyl chloride or anhydride in the presence of a Lewis acid catalyst.
Mechanism: Activation of the acyl group by coordination with the Lewis acid, followed by electrophilic aromatic substitution.
Application: Synthesis of various pharmaceuticals, including antipsychotics and antihistamines.

                                           6. Friedel-Crafts Alkylation:
Alkylation of aromatic rings using alkyl halides or alkenes in the presence of a Lewis acid catalyst.
Mechanism: Formation of a carbocation intermediate by the reaction of the alkyl halide with the Lewis acid, followed by electrophilic aromatic substitution.
 Application: Synthesis of natural products and pharmaceutical intermediates.

                                      7. Oxidation:
Increase in oxidation state, often involving the removal of electrons or addition of oxygen.
Mechanism: Various mechanisms depending on the specific oxidizing agent used (e.g., metal catalysts, peroxides, or enzymes).
Application: Conversion of alcohols to carbonyl compounds, a common transformation in pharmaceutical synthesis.

                                          8. Reduction:
Decrease in oxidation state, typically involving the addition of electrons or hydrogen.
Mechanism: Various mechanisms depending on the reducing agent used (e.g., metal catalysts, hydrides, or molecular hydrogen).
Application: Reduction of functional groups like carbonyls, imines, and nitro groups in the synthesis of pharmaceuticals.

                                         9. Claisen Condensation:
Formation of a β-keto ester or β-diketone by the reaction of esters or ketones with strong bases.
Mechanism: Deprotonation of the carbonyl compound, nucleophilic attack on the electrophilic carbon, and subsequent elimination of the leaving group.
Application: Synthesis of β-keto esters as key intermediates in pharmaceutical synthesis, particularly in the formation of polyketide natural products.

                                        10. Michael Addition: 
Addition of a nucleophile to an α,β-unsaturated carbonyl compound.
 Mechanism: Nucleophilic attack of the nucleophile on the β-carbon of the α,β-unsaturated carbonyl compound.
 Application: Construction of carbon-carbon bonds in the synthesis of pharmaceuticals and natural products.

                                        11. Suzuki-Miyaura Cross-Coupling:
Coupling of an organoboron compound with an organic halide or pseudohalide in the presence of a palladium catalyst.
Mechanism: Oxidative addition of the organic halide to the palladium catalyst, transmetallation with the organoboron compound, and reductive elimination to form the coupled product.
Application: Synthesis of biaryl compounds, a common motif in pharmaceuticals, including drugs for cancer and HIV.

                                           12. Heck Reaction:
Palladium-catalyzed coupling of an alkene with an aryl or vinyl halide to form a substituted alkene.
Mechanism: Oxidative addition of the aryl or vinyl halide to the palladium catalyst, insertion of the alkene, and reductive elimination to form the coupled product.
Application: Introduction of aryl or vinyl substituents in the synthesis of complex pharmaceutical molecules.

                                                       13. Hydroformylation (Oxo Process):
Addition of carbon monoxide and hydrogen to an alkene to form an aldehyde.
Mechanism: Formation of a metal carbonyl complex, migratory insertion of the alkene, and carbonylation to form the aldehyde.
Application: Synthesis of aldehydes as key intermediates in the production of pharmaceuticals and fine chemicals.

                                                     14. Buchwald-Hartwig Amination:
Palladium-catalyzed coupling of an aryl halide with an amine to form an aryl amine.
Mechanism: Oxidative addition of the aryl halide to the palladium catalyst, transmetallation with the amine, and reductive elimination to form the coupled product.
Application: Introduction of arylamine functionalities in the synthesis of pharmaceuticals, particularly in drug discovery and development.

                                                     15. Epoxidation:
Asymmetric epoxidation of alkenes using a chiral titanium complex and a peroxide oxidant.
Mechanism: Formation of a chiral epoxidation catalyst, coordination of the alkene to the catalyst, and epoxidation with the peroxide oxidant.
Application: Synthesis of chiral epoxides as versatile intermediates in pharmaceutical synthesis and natural product chemistry.

                                                       16. Coupling:
Palladium-catalyzed coupling of an organotin compound with an organic halide or pseudohalide.
Mechanism: Oxidative addition of the organic halide to the palladium catalyst, transmetallation with the organotin compound, and reductive elimination to form the coupled product.
Application: Formation of carbon-carbon bonds in the synthesis of pharmaceuticals and materials.

                                                        17. Diels-Alder Reaction: 
A cycloaddition reaction between a conjugated diene and a dienophile to form a cyclohexene derivative known as a cycloadduct.]
Mechanism: Concerted [Diels-Alder mechanism: A concerted pericyclic reaction where the diene and dienophile form new σ bonds simultaneously.]
Application: [Diels-Alder reaction application: Widely used in the synthesis of complex natural products and pharmaceuticals due to its efficiency in building ring structures.]

                                                   18. Sulfonation:
Addition of a sulfonic acid group (–SO3H) to an organic compound.
Mechanism: Nucleophilic substitution of a hydrogen atom with a sulfonate group.
Application: Introduction of sulfonic acid functionalities in the synthesis of pharmaceuticals, particularly in drug formulation and modification.

                                               20. Birch Reduction:
Reduction of aromatic rings using alkali metals in liquid ammonia, leading to formation of 1,4-cyclohexadienes.
Mechanism: Formation of radical anions followed by protonation and subsequent rearrangement.
Application: Preparation of dienes for use in the synthesis of natural products and pharmaceuticals.

                                                21. Knoevenagel Condensation:
Condensation reaction between an aldehyde or ketone and a compound containing an active methylene group.
Mechanism: Deprotonation of the active methylene compound, nucleophilic attack on the carbonyl carbon, and dehydration.
Application: Synthesis of unsaturated compounds as intermediates in pharmaceutical synthesis.

                                               22. Wittig Reaction:
Reaction of a phosphonium ylide with a carbonyl compound to form an alkene.
Mechanism: Formation of a betaine intermediate, followed by Wittig olefination to form the alkene.
Application: Synthesis of alkenes as key intermediates in the production of pharmaceuticals and natural products.

                                              23. Suzuki Coupling:
Palladium-catalyzed coupling of an organoboron compound with an aryl or vinyl halide.
Mechanism: Oxidative addition of the aryl or vinyl halide to the palladium catalyst, transmetallation with the organoboron compound, and reductive elimination to form the coupled product.
Application: Formation of biaryl compounds as important motifs in pharmaceuticals and materials science.

                                           24. Hofmann Rearrangement:
Conversion of primary amides to primary amines through reaction with halogens and base.
Mechanism: Formation of an isocyanate intermediate, followed by rearrangement and hydrolysis.
Application: Preparation of primary amines as intermediates in pharmaceutical synthesis and organic chemistry.

                                              25. Ugi Reaction:
Multicomponent reaction involving an amine, an aldehyde, an isocyanide, and a carboxylic acid to form a peptidomimetic.
Mechanism: Formation of an imine, followed by addition of the isocyanide and carboxylic acid, and finally cyclization.
Application: Diversity-oriented synthesis of small molecules for drug discovery and development.

These reactions showcase a range of transformations commonly employed in pharmaceutical synthesis, enabling the construction of complex molecules with therapeutic potential.