146 



Essays in Biochemistry 



written for the benzoate ion (scheme VII), it will be noted that the 

 phenyl group can participate in the resonance picture only when a 

 charge separation is invoked. 



f\.. 



(VII) 



If it is assumed that forms involving a charge separation make only 

 a minor contribution to the respective anions, it becomes apparent that 

 there are more forms contributing to the resonance hybrid of the 

 5-phenyltetrazolyl anion than to the benzoate ion. On this basis it 

 is suggested that the resonance stabilization of the 5-phenyltetrazolyl 

 anion is sufficiently great to overbalance the lesser electronegativity 

 of nitrogen as compared with oxygen and cause 5-phenyltetrazole to 

 be a stronger acid than benzoic acid. It is also conceivable that 

 resonance phenomena due to the withdrawal of electrons from the 

 tetrazole ring by the phenyl group may cause a reversal of the direction 

 of the inductive effect ordinarily associated with the phenyl group, 

 thereby increasing the electronegativity of the tetrazolyl group and 

 effectively lowering its proton affinity. Following the same reasoning 

 the 5-aryltetrazoles should generally be stronger acids than the corre- 

 spondingly substituted benzoic acids. 



Particularly striking is the effect of orientation of substituent groups 

 upon the apparent dissociation constants of the 5-aryltetrazoles. In 

 the several series for which data are available the dissociation con- 

 stants decrease in the order meta > ortho > para. Furthermore, in 

 the aryltetrazole series the ortho and para substituted compounds are 

 of approximately the same strength. One exception must be noted: 

 5-p-methoxyphenyltetrazole is about ten times as strong an acid as 

 the ortho isomer, a reversal of the situation existing with the methoxy- 

 benzoic acids. An explanation of this observation will be advanced 

 later. Because of their insolubility in 50% methanol it was necessary 

 to determine acidic dissociation constants of 5-p-chlorophenyl- and 

 5-p-bromophenyltetrazole in 75% methanol. However, dissociation 

 constants determined in both solvent mixtures in several other instances 

 indicated that the values in 50% methanol were about twice as large 

 as those in 75% methanol. Consequently, it seems reasonable to 

 double the values of the apparent dissociation constants measure in 



