Synthesis of 4-arylcarbamoyl-5-(2-hydroxynaphthylazo)imidazoles and 1-substituted naphtho[2,1-e]imidazo[5,1-c][1,2,4]triazines

Abstract

The reactions of β naphthol with 5 diazoimidazoles and imidazolyl 5 diazonium salts containing chemically different carboxamide groups in position 4 were studied. Hetero cyclization of 4 arylcarbamoyl 5 (2 hydroxynaphthylazo)imidazoles formed in these reac tions was investigated. The presence of the NH fragment in the amide group prevents this process, the reaction giving instead 3 substituted 3,7 dihydroimidazo[4,5 d] [1,2,3]triazin 4 ones, which is due to reversibility of C azo coupling. Methods for modification of 1 ethoxy carbonyl group in the naphtho[2,1 e]imidazo [5,1 c] [1,2,4]triazine system were developed and used to prepare substituted carboxamides inaccessible by other routes.It is known 1,2 that azo compounds based on diazo nium derivatives of pyrazole, triazole, tetrazole, and phenols or naphthols undergo intramolecular cyclization upon refluxing in methanol, glacial acetic acid, or 2 M sulfuric acid to give azolotriazines, whereas in the reac tion of 2 diazoimidazole with β naphthols, the cycliza tion product is formed already under azo coupling condi tions.The purpose of this work is to study the reactivity of 5 diazoimidazole 4 carboxamides 1a-h and imidazolyl 5 diazonium salts 2a-d containing chemically differ ent substituents in the carboxamide fragment toward β naphthol and to synthesize new naphtho[2,1 e]imid azo[5,1 c] [1,2,4]triazines based on the C azo coupling products obtained. 1a-h, 2a-d: R = NHC 6 H 4 Z, Z = p Me (a), p Cl (b), p OMe (c), p COOEt (d); R = NHC 6 H 11 (e), NHMe (f), (g),It should be emphasized that, when performing azo coupling with 5 diazoimidazoles 1a-f having an NH frag ment in the amide function, one should be aware of the possible formation of intramolecular cyclization prod ucts, namely, imidazo[4,5 d][1,2,3]triazin 4 ones. This type of cyclization is known 3 to take place almost instan taneously in highly acidic or alkaline media (рH <1, pH >7) or on heating and to be retarded at рH values from 1 to 6 and temperatures not exceeding room tem perature.Our study of the reactions of 5 diazoimidazole 4 (N substituted)carboxamides 1a-h with β naphthol has shown that the formation rate and the yields of products are markedly affected by the structure of the carboxamide substituent. By long term keeping of the reaction mixture at room temperature in dry acetonitrile, we were able to couple β naphthol only with diazoimidazoles 1e-h con taining aliphatic substituents in the amide part of the molecule (Scheme 1). This gave 5 (2 hydroxynaphthyl azo) 4 morpholinocarbonylimidazole (3g) and 5 (2 hydr oxynaphthylazo) 4 piperidinocarbonylimidazole (3h) in 54 and 48% yields, respectively (Table 1). Azo compounds 3e,f were formed together with imidazo[4,5 d] [1,2,3]tri azin 4 ones 4e,f in 33 and 42% yields, respectively. However, upon the reaction of 5 diazoimidazole 4 (N aryl)carboxamides 1a-d with naphthol under similar conditions, only traces of azo compounds were detected by chromatography. Only 3 substituted 3,7 dihydro imidazo[4,5 d] [1,2,3]triazin 4 ones 4a-d were isolated fro...