医薬品の分解とその安定化(第4報) : アミノアルキルエステルの構造と安定性についてその2

概要

論文の詳細を見る
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, k_<OH> at 60° being 0.13 in II and 0.08 l/mole/hr in IV, and about 10^4 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.
公益社団法人日本薬学会の論文
1970-08-25