142 Essays in Biochemistry 



NH 2 ). The development of this reaction was aborted by von Braun's 

 observation that its application to alkyl and aryl cyanides in the 

 presence of a large excess of concentrated sulfuric acid led to rearranged 

 products such as 1-alkyl- or l-aryl-5-aminotetrazoles (scheme II). 

 Although the conditions under which von Braun's experiments were 

 done were entirely different from those applied by earlier workers, von 

 Braun did not hesitate to conclude that hydrazoic acid would not add 

 to the cyanide group of alkyl or aryl cyanides. 



HSO R— N- -C— NH 2 

 RCN + 2HN 3 -^-4 | || + N 2 (II) 



N N 



\ / 



N 



R = alkyl or aryl 



Recent investigations have shown that von Braun's conclusions are 

 not tenable. As a result the addition of hydrazoic acid to nitriles has 

 become the most generally applicable procedure 2 5 for the synthesis 

 of 5-substituted tetrazoles. The symbol R in scheme I may be re- 

 defined to include in addition to the groups mentioned alkyl and aryl, 

 alkyl- or arylamino, and dialkyl- or diarylamino groups. It must be 

 pointed out, however, that in one instance, when R is a monoalkyl- 

 or monoarylamino group as in the monoalkyl- or monoarylcyanamides, 

 cyclization of the imide azide may take place in either of two ways 

 and the course shown in scheme III is followed exclusively. 4 It is 

 particularly interesting to note that the nature of the group R in the 

 monosubstituted cyanamides appears to have little effect upon the 

 course of the cyclization illustrated in scheme III. 



RNH— CN 



With the accumulation of a group of 5-substituted tetrazoles the 

 determination of their apparent acidic dissociation constants by po- 

 tentiometric titrations could be undertaken. It soon became apparent 

 that the 5-tetrazolyl group ( — CN 4 H) was quite comparable to the 

 carboxyl group ( — C0 2 H) in bestowing acidic character upon com- 



