Tetrazoles as Carboxylic Acid Analogs 149 



Although the o-halobenzoic acids are many times stronger than the 

 p-halobenzoic acids, the 5-o-halophenyl- and 5-p-halophenyltetrazoles 

 are of about the same strength as acids. This probably represents a 

 marked reduction of the strength of the orf/io-substituted compound 

 rather than a large increase in the strength of the para isomer. Con- 

 ceivably the relatively low dissociation constants of the 5-o-halo- 

 phenyltetrazoles are manifestations of the bulk effect of the ortho 

 substituents. The tetrazole ring structure may be sufficiently rigid 

 to cause a moderately bulky group in the ortho position of the 5-phenyl 

 substituent to interfere with the formation of structures in which the 

 two rings are coplanar. Resonance forms involving both the tetrazole 

 and the benzene rings simultaneously require coplanarity of the rings. 



The small dissociation constant of 5-o-methoxyphenyltetrazole as 

 compared with the para isomer may be due to hydrogen bonding 

 between the methoxyl oxygen and the acidic hydrogen of the tetrazole 

 ring (scheme X). This effect is much more pronounced in the 5-aryl- 



N— N 



N— N (X) 



\ 



H 



\ 

 CH 3 



tetrazole series than in the benzoic acid series. In the undissociated 

 forms of the 5-substituted tetrazoles the acidic hydrogen is held in 

 the plane of the ring at a rather fixed angle in position 1 or 2 owing 

 to the rigidity of the tetrazole ring structure. When the acidic hydro- 

 gen is located at position 1, the rigidity of the ring would force the 

 hydrogen into a position favorable for hydrogen bonding with a sub- 

 stituent in the ortho position of a 5-phenyl group. Such hydrogen 

 bonding would serve to increase the stability of the undissociated 

 molecule and thus decrease the apparent dissociation constant of the 

 compound. 



The effect of an amino group or a substituted amino group as sub- 

 stituents in the 5-position of the tetrazole ring is particularly interest- 

 ing. Such compounds are analogous to the carbamic acids in the 

 carboxylic acid series. The instability of the latter precludes com- 

 parisons. The substitution of an amino group in the 5-position of the 

 tetrazole nucleus causes a marked decrease in acid strength (Table 3). 

 Furthermore, it may be noted that the basic function of the amino 



