Additive Tendency of Substituent Effects onto Rate Constant of Acidic Hydrolysis of Methyl 4‐O‐Methyl‐β‐d‐Glucopyranoside

Abstract All eight types of differently methyl‐substituted methyl 4‐ O ‐methyl‐β‐ d ‐glucopyranosides were chemically synthesized, analytically characterized including 13 C NMR analysis, and subjected to acid‐catalyzed hydrolytic cleavage of the glucosides. The 13 C NMR resonances of the ring‐carbons shift apprx. 10 ppm down‐field by methyl substitution. Acid hydrolysis (3 mol⋅L −1 DCl/D 2 O) was followed by 1 H NMR to determine the rate constants ( k ) which all were of first order. Methyl substitution at any position (2‐ O , 3‐ O and 6‐ O ) was found to have a simple additive effect on the reaction rate. This was also shown as a linear free energy relationship (LFER). The substituent effects upon mono‐substitution depend on the substitution position: 2‐ O ‐methyl or 6‐ O ‐methyl substitution decreased the reaction rate, while 3‐ O ‐methyl substitution accelerated the hydrolysis. In cases of di‐ or tri‐substitutions these effects were additive.