医薬品の分解とその安定化(第3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1

概要

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Kinetic parameters with respect to the stability of the aminoethyl esters of phenyl acetic acid were measured and the following facts were revealed. 1) Stability of these esters is affected by the substituent in 2-position of phenylacetic acid. The greater the size of this substituent, the smaller became the reaction constants, k_H and k_<OH>, and greater the ΔEa and ΔS. Also k<H2O> became broader as will be seen from the pH -rate profile in Fig.2 and 3. 2) Esters of tertiary amine type have greater rate of hydrolysis than those of quaternary ammonium salt type, the rate in alkaline side being about 100 times greater in the tertiary amine-type esters. 3) There is a linear relationship between λ (polar substituent constant) of R in C_6H_5-CHRCOOCH_2CH_2N(C_2H_5) and k_H or k_<OH>, as shown in Fig.7 and 8,the Taft formula can be applied to it. 4) There is a linear relationship between the pK_a and hydrolysis rate of C_6H_5CHRCOOH, as shown in Fig.9. 5) In the above 3 and 4,compounds with R as sec-butyl or diphenyl deviate from linearity and steric effect of the substituent has retarded the hydrolysis rate of these compounds.
公益社団法人日本薬学会の論文
1970-08-25