The synthesis of certain 5-aminotetrazole derivatives. I. The action of hydrazoic acid on some dialkylcyanamides

Abstract

While 5-aminotetrazole has been known for many years (1), its derivatives in which amino hydrogens are replaced by alkyl groups are not, in general, known. A study of this class of compounds, the 5-monoand 5-di-alkylaminotetrazoles, is of interest for several reasons. Since the parent substance, 5-aminotetrazole, possesses both an acidic and a basic function, it would be interesting to know the effect of substituents on these functions. Furthermore, alkylation of 5-aminotetrazole leads to a mixture of products (2) and there is need for a direct, unequivocal synthesis of these derivatives. The possibility that this class of compounds might have useful pharmacological activity also seemed attractive.The synthesis of 5-aminotetrazole and some of its substituted derivatives has been accomplished by a number of methods. The parent compound was first obtained by Thiele (1) through the action of nitrous acid on aminoguanidine. The reaction involved the initial formation of guanyl azide which readily cyclized to form 5-aminotetrazole. Busch and Bauer (3) have applied an analogous reaction to N,N,-diaryl-Nv,-aminoguanidines and have reported the formation of 1 -aryl-5-arylaminotetrazoles. Recently a similar sequence of reactions has been applied to N-nitro-N'-aminoguanidine for the preparation of 5-nitraminotetrazole (4).The direct formation of 5-aminotetrazole by the addition of hydrazoic acid to cyanamide was observed by Hantzsch and Vagt (5). It was suggested that the reaction involved the formation of guanyl azide through addition of hydrazoic acid to the cyanide group followed by immediate cyclization of the intermediate. Stollé (6) has applied the same type of reaction to several phenylalkylcyanamides and has described the formation of the corresponding 5-aminotetrazoles in which the amino hydrogens were replaced by a phenyl and an alkyl group.The formation of 5-substituted tetrazoles by addition of hydrazoic acid to the cyano group of nitriles has become recognized as a general procedure through the studies of Dimroth and Fester with hydrocyanic acid (7), Oliveri-Mandalá with cyanogen, cyanogen bromide, and ethyl cyanoformate (8), and Mihina and Herbst with an extensive group of alkyl and aryl cyanides (9). In an attempt to prepare 5-alkyltetrazoles from nitriles by interaction with hydrazoic acid in the presence of concentrated sulfuric acid von Braun and Keller (10) observed the 1 Based on a thesis submitted to the School of Graduate Studies at Michigan State College in 1952 by William L. Garbrecht in partial fulfillment of the requirements for the degree of Doctor of Philosophy.

Biological Activity of Tetrazole Analogues of Indole-3-Acetic Acid and 2,4-Dichlorophenoxyacetic Acid

“…Aln extensive progranm of synthesis and testing oI tetrazoles has been conducted by Herbst and associates (2,3,5,7,15). Tetrazoles substituted only in the ring carbon (R-CN4H) are acids having one dissociable hydrogen.…”

New heteroatom-rich ring systems from N,N-dialkyl-N’-chlorosulfonyl chloroformamidines

“…Dimethylcyanamide 4a, diethylcyanamide 4b, piperidine-1-carbonitrile 4c, and pyrrolidine-1-carbonitrile 4d, are commercially available, which allows convenient use of these compounds, but other dialkylcyanamides 4 are readily prepared from either the reaction between cyanogen bromide and various secondary amines, such as N-benzyl-N-methylcyanamide 4e (Scheme 4), 22,23 or by the direct alkylation of cyanamide with various alkyl halides (Scheme 5). 23,24 …”

Synthesis and chemical transformations of mono- and disubstituted cyanamides

“…The products are disubstituted cyanamide and dialkylammonium salt [16][17][18]. Ammonium salts formed in the cyanation of amines are capable of reacting with cyanamides to give guanidine derivatives; as a result, the yield of the target product decreases.…”