With Other Amides, Nitriles, or Imidates

Niementowski found that no other amide reacted so freely with o-amino-amides as did formamide and that the difficulty increased with each carbon atom added to the acyl group.279 To introduce a C-aryl substituent, it is preferable to heat an oacylamino acid with formamide. Thus, 2-benzamido-benzoic acid, in formamide at 160°C for 3 hr, gave a good yield of 2-phenyl-quinazolin-4-one.293 However, the use of formamide to condense 2-acetamidobenzoic acid resulted in a mixture of two products, one with 

Thioamides, which react much more vigorously than amides, provide the best solution to the problem of preparing 2-substituted quinazolin-4-ones. Thus, thioacetamide and anthranilic acid gave an excellent yield of 2-methylquinazolin-4-one when fused together at 155°C for 30 min,295 and thiobenzamide gave a quantitative yield of the 2-phenyl analog (160°C, 2 hr).296 

Nitriles and imidates have found little use, so far. Heating propionitrile and 2-aminobenzoic acid at 210°C in a closed vessel gave only a low yield of 2-methylquinazolin-4-one.297 Anthranilic add and 10 of its C-substituted derivatives were refluxed (5-50 hr) with ethyl acetimidate and benzimidate in methanol to give 2-methyl- and 2-phenylquinazolin-4-ones, respectively, in moderate yields three aminopyridine carboxylic acids behaved similarly.298 JV-Phenylbenzimidoyl chloride [PhC(NPh)Cl] and ammonium 2-aminobenzoate, in cold acetone, produced 2,3-diphenylquinazolin-4-one in good yield.299 

---