Degradation Kinetics of (±)-4′-Ethyl-2-methyl-3-(1-pyrrolidinyl)propiophenone Hydrochloride (HY-770) and Structure–Stability Relationship among its Analogues in Aqueous Solution

The kinetics and pathways for degradation of (±)-4′-ethyl-2-methyl-3-(1-pyrrolidinyl)propiophenone hydrochloride (HY-770; 1), a newly developed muscle-relaxing agent, and its analogues were studied in aqueous solution at 50°C, ionic strength 0.5 M, and pH 8.0–12.0. Compound 1 and its four analogues followed pseudo-first-order degradation kinetics at constant pH and temperature. From the analysis of the pH degradation–rate profiles, it is evident that specific hydroxide ion-catalyzed degradations of ionized and un-ionized species occur for 1 and its structural analogue, 3′-fluoro-2-methyl-3-(1-pyrrolidinyl)propiophenone hydrochloride (HN-961;5). The hydroxide ion-catalyzed degradation of the ionized species was found to be 100 times faster than that of the un-ionized species and to be the major process at pH < 9.0. On the contrary, 1 was extremely stable in 0.5 M HCl at 50°C, suggesting that the hydronium ion-catalyzed degradation and the spontaneous degradation of the ionized species is negligible. The Arrhenius plot for the degradation of 1 at 35–50°C and pH 9.0 showed that the apparent energy of activation was 22.0 kcal/mol. The degradation rates of the five structural analogues were significantly dependent on the electron withdrawing effect of the benzene substituents of the molecule.