In order to follow the correlation between stability and chemical structure of aminoalkyl esters, examinations were made on the effect of steric hindrance near the ester linkage on hydrolysis. Four kinds of phenylacetic acid derivatives having a quaternary carbon in 2-position were synthesized and their stability was examined. Alkaline hydrolysis of 2-diethylaminoethyl 2-ethyl-3-methyl-2-phenylvalerate methobromide (II) and 2-diethyl-aminoethyl 3-methyl-2-phenyl-2-propylvalerate methobromide (IV) is a second-order reaction when molar ratio of ester to alkali is 1 : 1, while that in KCl-NaOH buffer solution of pH 12.5 is a pseudofirst order reaction. This mechanism is the same as in the case of other phenylacetic acid esters with less steric hindrance. Alkaline hydrolysis of II and IV was quite slow, kOH at 60° being 0.13 in II and 0.08 l/mole/hr in IV, and about 104 times more stable than Valethamate Bromide. The activation entropy was -19.9 in II and -20.8 cal/mole/deg in IV, these values being very small. Acid hydrolysis of all these four compounds was extremely small, almost no hydrolysis being found at around 1, 200 hours at pH 0.7. These data indicate that the presence of a steric hindrance in the position close to the ester linkage is very effective in stabilization of aminoalkyl esters.
