THE KINETICS AND MECHANISM OF THE HYDROLYSIS OF CYCLOPENTOLATE HYDROCHLORIDE IN ALKALINE-SOLUTIONS

Cyclopentolate hydrochloride (Cy . HCl) is an ester of a substituted b enzeneacetic acid, having N,N-dimethylaminoethanol as the alcohol moie ty. A reversed-phase HPLC assay was employed to investigate the kineti cs of degradation of Cy . HCl. The influence of pH, buffers, and tempe rature was studied in alkaline solutions. The degradation follows (pse udo) first-order kinetics at 50 degrees C. Results indicate that it de grades very rapidly at higher pH values. Phenylacetic acid and alpha-( 1-hydroxycyclopentyl)benzeneacetic acid were isolated and identified a s the degradation products. The reaction mechanism appears to follow a parallel scheme where phenylacetic acid and alpha-(1-hydroxycyclopent yl)benzeneacetic acid are formed simultaneously. It is proposed that a lpha-(1-hydroxycyclopentyl)benzeneacetic acid is formed by normal este r hydrolysis. Phenylacetic acid is formed via a six-membered transitio n state and its formation requires the assistance of the hydroxyl grou p from the adjacent cyclopentanol moiety.