Steric Effects of Substituents at the 2- and 4-Positions

A 2-Alkyl group contributes to the basicity of the thiazole ring. The only significant fall in pK (for 2- -propyl and 2-r-butyl thiazole) is not 

If the rate constants for quaternization of 2-alkylthiazoles depended on electronic factors, they would all be greater than that of thiazole, which has the low est pK. and all of the same order. The decrease in rate constants that is observed is attributed wholly to steric effects. In Table III-50 we report the main parameters for the reaction of 2-alkylthiazoles with methyl iodide. 

TABLE m-50. RATE CONSTANTS AND ACTD ATION PARAMETERS FOR THE REACTION OF 2-ALKYLTHl AZOLES WITH METHYL IODIDE IN NITROBENZENE (256) 

A good correlation between log fc/fcp is the rate constant for methylthiazole), and the Taft s parameter (261J has been found for this series. Table IIT51 indicates this correlation. 

388 Alkyl. Aryl. Aralkyl, and Related Thiazole Derivatives 

---