152 



Essays in Biochemistry 



that of two ethyl groups as in 5-diethylaminotetrazole, the anticipated 

 increase in acid strength is realized. 



As has been pointed out, the enhanced acidity of 5-phenyltetrazole 

 arises from increased stabilization of the anion by virtue of the con- 

 jugation of the tetrazole nucleus and the phenyl group. When the 

 two groups are separated by an amino group, the resulting 5-phenyl- 

 aminotetrazole is a weaker acid than 5-phenyltetrazole because the 

 conjugation of the phenyl group and the tetrazole nucleus is interrupted 

 by the amino group. (It is interesting to note that separation of the 

 phenyl group and the tetrazole nucleus by a methylene group produces 

 very nearly the same quantitative effect.) The fact that 5-phenyl- 

 aminotetrazole is still more acidic than 5-aminotetrazole and its alkyl 

 derivatives leads one to speculate that resonance forms such as those 

 illustrated in scheme XII may be responsible. Such forms would be 



H 



H 



H 



C— N= 



+ 



N— N 



/ 



\ 



N— N H 



\ I 



C— N= 



N— N' 



/ 



+ 



(XII) 



expected to increase the electronegativity of the tetrazole nucleus in- 

 ductively and result in a decrease in proton affinity. This speculation 

 is given some weight by the relative acidities of the isomeric 5-nitro- 

 phenylaminotetrazoles. The inductive effect just cited should be aug- 

 mented in decreasing order by the ortho, meta, and para nitro groups. 

 Superimposed on this effect is a resonance reinforcement in the case 

 of the ortho and para isomers. This combination of effects should cause 

 the o-nitrophenylaminotetrazole to be the strongest acid, the para 

 intermediate in strength, and the meta the weakest. All of them should 

 be distinctly stronger acids than 5-phenylaminotetrazole. This is also 

 the observed order. In scheme XIII several possible contributing 

 forms for the resonance hybrid of 5-p-nitrophenylaminotetrazole are 

 illustrated. 



H 



H 



N— N 



O N— N 



/- 



H 



C— N= 



o 



=N 



0" 



(XIII) 



