Tetrazoles as Carboxylic 

 Acid Analogs 



ROBERT M. HERBST 



The acidic character of the tetrazole ring system in which the ring 

 nitrogens are unsubstituted has been recognized since the first prep- 

 aration of the parent compound by Bladin in 1892. Although Bladin 

 had suggested the name tetrazole for the ring system in 1886, the 

 parent compound was for many years referred to as "tetrazotsaure" 

 because of its acidic character. The acidic nature of several 5-substi- 

 tuted tetrazoles was similarly recognized by nomenclature such as 

 "benzenyl tetrazotsaure" (5-phenyltetrazole) and "amidotetrazot- 

 saure" (5-aminotetrazole). Although it w r as recognized with the first 

 preparation of these compounds that 5-substituted tetrazoles behaved 

 as acids, it is only recently that a systematic study of the factors 

 influencing the acid strength of these compounds has been undertaken. 

 An attempt will be made to develop the analogy between the factors 

 influencing the acidity of 5-substituted tetrazoles and carboxylic acids 

 in the following. 



Until recently, with few exceptions, only the 5-aryltetrazoles have 

 been easily accessible. These were usually prepared by a sequence 

 of reactions due to Pinner that involved the conversion of a nitrile 

 successively into an iminoester, a hydrazidine, an imide azide, and 

 finally a tetrazole. It was also known that certain nitriles such as 

 cyanogen, cyanogen chloride, ethyl cyanoformate, and cyanamide could 

 be converted into the corresponding 5-substituted tetrazoles by inter- 

 action with hydrazoic acid (scheme I, R = H, CN, CI, COOC2H5, 



R— C=NH HN- — C— R 

 RCN-^ I -> I (I) 



N 3 N N 



\ / 



N 



141 



