MECHANISM OF THIAZOLIDINE HYDROLYSIS - RING-OPENING AND HYDROLYSIS OF 1,3-THIAZOLIDINE DERIVATIVES OF PARA-(DIMETHYLAMINO)CINNAMALDEHYDE

The hydrolysis reactions of 2-(p-(dimethylamino)styryl)-1,3-thiazolidine and the corresponding N-butyl and N-phenyl derivatives in the pH range 1-12 proceed via the iminium ion intermediate formed in an equilibrium ring-opening reaction. Such an intermediate was detected spectrophotometrically (lambda-max = 480-525 nm). The fast formation of the iminium ion in ring opening of the N-phenyl-1,3-thiazolidine could be monitored at pH 3-10. Ring opening involves a pH-independent reaction at pH > 4, which proceeds 2.25-fold slower in D2O than in H2O, and hydronium ion catalysis at low pH. General acid catalysis in ring opening was observed with acetic acid buffers. Ring opening of the N-butylthiazolidine occurs 250-fold more rapidly than with the N-phenyl derivative. The plot of log k0 vs pH for aldehyde formation from the N-butyl-substituted thiazolidine has five unit changes in slope. The hydrolysis reactions subsequent to ring opening proceed with (a) attack of OH- on the zwitterion (ionized thiol group) at high pH, (b) attack of OH- on the positively charged species (un-ionized thiol group) at pH < 10 (or the kinetically equivalent attack of water on the zwitterion), (c) attack of water on the positively charged species at pH < 5, and (d) attack of water on the protonated dipositive species at low pH. There is an apparent pK of 6.3 in the hydrolysis reactions (aldehyde formation) of the N-butyl-substituted thiazolidine, which is a complex constant governing the reversible ring opening and protonation. The stability of the iminium ion intermediate has great influence on the shape of the pH-rate constant profiles and the interpretation of the apparent pK values. The hydrolysis of 2-(p-(dimethylamino)phenyl)-N-acetyl-1,3-thiazolidine at 90-degrees-C is pH independent from pH 1-4 and hydronium ion catalyzed at pH > 4. The reaction involves rate-determining ring opening, which is due to the poor stabilization of the developing carbonium ion when there is an N-acetyl substituent.