(BQ) Part 2 book "Advanced practicial medicinal chemistry" presents the following contents: Synthesis of medicinal compounds (acetylation methods, benzoylation methods, sulphonylation methods, selected medicinal compounds, organic name reactions, condensation reactions,.), | CHAPTER 4 Syntheses of Medicinal Compounds ACETYLATION METHODS Introduction The replacement of ‘active hydrogen’ of compounds belonging to the class ROH (phenols or alcohols), in addition to compounds of the category RNH2 and R2NH (., primary- and secondary-amines may be acetylated directly, whereby the reactive H-atom is specifically O | | replaced by the acetyl radical, — C — CH 3 . This replacement of an active hydrogen by an acetyl function is termed as acetylation. In true sense, the acetylation of alcohols and phenols is really regarded as a specific instance of esterification by virtue of the fact that the resulting acetyl derivative O | | ., R—O— C — CH 3 , is, evidently an ‘ester’ of acetic acid. Likewise, the primary and secondO | | ary amines give rise to the corresponding acetyl derivatives of the type RNH— C — CH 3 and O | | R2N— C — CH 3 , respectively, that may be regarded as mono- and di-substituted derivatives O | | of acetamide ., H2N— C — CH 3 . In actual practice, acetylation may be accomplished by two major procedures, namely : Procedure–I. Heating with a mixture of Acetic anhydride and Acetic acid : It has been observed that when a primary or secondary amine is reacted with glacial acetic acid by the application of heat, the corresponding acetyl derivative is obtained ; however, the ensuring reaction is invariably found to be extremely sluggish and slow, as given below : 67 P-IV\C:\N-ADV\CH4-1 68 ADVANCED PRACTICAL MEDICINAL CHEMISTRY If, acetic anhydride is mixed with glacial acetic acid in equal proportions (1 : 1) the acetylation proceeds with a remarkable rapid and fast manner, as shown below : O O O O CH3—C CH3—C—OH RNH H + O → RNH— C — CH 3 + CH 3 C — OH Glacial acetic acid pri-amine CH3—C O Acetic Anhydride This is due to the fact that acetic anhydride is much more reactive than glacial acetic acid alone ; and the presence of the latter helps the reaction to proceed in the forward .
