KINETICS OF DECOMPOSITION OF O-ACYL DERIVATIVES OF SALICYLAMIDE AND RELATED-COMPOUNDS

被引：2

作者：

TAWFIQ, FA ^{[1
]}

HUSSAIN, A ^{[1
]}

DITTERT, L ^{[1
]}

CROOKS, PA ^{[1
]}

机构：

[1] UNIV KENTUCKY,COLL PHARM,LEXINGTON,KY 40536

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 1990年 / 64卷 / 01期

关键词：

Decomposition kinetics; Intramolecular rearrangement; Salicylamide O-acyl derivative; Transacylation;

D O I：

10.1016/0378-5173(90)90177-6

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Salicylamide hemisuccinate ethyl ester, salicylamide hemiglutarate methyl ester, O-acetyl-N-methylsalicylamide, and O-acetyl-N, N-diethylsalicylamide were synthesized, and the kinetics and mechanisms of their decompositions in aqueous buffers at various pH values were studied. The results support a mechanism in which the predominant feature is a transacylation reaction involving intramolecular attack of the amide anion on the carbonyl carbon of the neighboring ester group. In the case of O-acetyl-N-methyl salicylamide and O-acetyl-N,N-diethylsalicylamide, where the ionization of the amide group is blocked, the predominant reaction was found to be hydrolysis of the ester groups rather than O-to-N-acyl transfer. The reaction rates for the glutarate hemiester were found to be faster than those for the corresponding ethyl ester at pH values around 7.0. These results confirm a previously proposed mechanism in which a second intramolecular general acid catalysis involving the free carboxyl group on the hemiester moiety accelerates the transacylation rate. © 1990.

引用

页码：45 / 53

页数：9

共 6 条

[1] O-ACYLSALICYLAMIDES AS POSSIBLE PRODRUGS FOR SALICYLAMIDE .1. KINETICS AND MECHANISMS OF THEIR DEGRADATION AND REACTION WITH ENZYMES AND SODIUM BISULFITE [J].