Effect of a Group Adjacent to an Ortho-Substituent

The results of kinetic studies of the quatemization of 4-alkyl-2,5-dimethylthiazoles do not give a linear correlation between log(fc/ko) and Tafts Es parameter, such as is found for 2-alkyl-, 4-alkyl-, and 2,4-dialkylthiazoles (258). 

The log(k/ko) value for 4-isopropyl-2,5-dimethylthiazole is twice that expected if the curve were linear, which implies a rate constant 6.5 times smaller than expected. This result can be explained by the existence of a privileged conformation, induced by the presence of the methyl group in the 5-position and that has a lower reactivity (258). This result also leads to a limitation in the use of Tafts Eg parameter to cases where the environment of a substituent does not induce particular conformation for this latter (258). 

Aralkyl, and Related Thiazole Derivatives 

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