Ammonolysis of a-Halogeno Carbonyl Compounds

This method has been widely used for the preparation of pyrazines, and was first employed by Staedel and Riigheimer (10) for the preparation of 2,5-diphenylpyrazine (9) from co-chloroacetophenone (7) and aqueous ammonia. 

Reactions of such chloro compounds with ammonia also produce some secondary amines. Thus Gabriel (166) examined the reaction of co-bromoacetophenone 

A similar reaction involving co-bromoacetophenone and benzylamine has been studied by Mason and Winder (26). The monophenacylbenzylamine hydrobromide (13) (from the reagents) with potassium hydroxide at 100° was claimed incorrectly to form 1,4-dibenzyl-2,5-diphenyl-l, 4-dihydropyrazine (14) (see p. 344), which gave 2,5-diphenylpyrazine. Bromopyruvic acid with aqueous ammonia and mercuric chloride at 55° gave 2,5-dicarboxypyrazine (236a). 

The reaction of a-chloro carbonyl compounds with ammonia is not always successful, for example, w-chloro-o-methoxyacetophenone and w-chloro-o,p-dimethoxyacetophenone yield only resinous products (236), but in these cases potassium phthalimide may be used for the ammonation to the a-amino carbonyl compound. This last method was developed by Gabriel (116) and co-workers (187). 

Attempted preparations of the parent compound, pyrazine, from halogeneoacetal-dehyde and ammonia were not very successful (23, 237). Tschitschibabin and Schtschukina (237) made a careful study of this reaction their best yield, after oxidation with mercuric salts, was not higher than 11%. Some pyrazines prepared by this method are listed in Table 11.3 (3,10, 23,31,166,193, 209,236-247). 

---

TABLE II.3 PYRAZINES PREPARED BY AMMONOLYSIS OF a-HALOGENO CARBONYL COMPOUNDS... 

---