Page - (000039) - in Biomedical Chemistry: Current Trends and Developments

Scheme 1.1.23: Synthesis of Nitrofurantoin from 5-nitrofuran-2-carbaldehyde and 1- aminoimidazolidine-2,4-dione. The reaction steps are the same as in any other nucleophilic carbonyl addition reaction followed by dehydration: 1. nucleophilic attack of the nucleophilic amino moiety to the electrophilic carbonyl carbon; 2. deprotonation of the positive nitrogen atom and protonation of the negative oxygen atom; 3. elimination of water by protonation of the hydroxyl group and deprotonation at the nitrogen atom. This synthetic route as a whole is a condensation reaction: two molecules produce a larger molecule with the loss of a small molecule, in this case water. In fact, imine and hydrazone synthesis are condensations too, but were introduced as additions (see above) since the condensation product is often readily generated from the unstable addition product unless very strict reaction conditions are used. 1.1.1.4.6 Acyl Substitution Reactions Acyl substitutions are another class of reactions involving carbonyl groups (Scheme 1.1.24). An acyl substitution reaction is favoured over a simple addition whenever an electronegative group is attached to the carbonyl group. This property is a main feature presented by carboxylic acids and their derivatives.