AbstractKinetics of acid‐catalyzed heteronucleophilic substitution and racemization of enantiomeric MeOX in ethanol and enantiomeric EtOX in methanol were studied by quenching reaction products at various times by neutralization. Enantiomeric contents of remaining substrate and reaction product were determined by chiral stationary phase high‐performance liquid chromatography. The experimental procedure allowed the determination of the stereoselectivity (i.e., the enantiomeric ratio of a substitution product formed from an enantiomerically pure substrate) involved in the heteronucleophilic substitution reactions. The stereoselectivity was found to vary between 58:42 and 87:13, depending on the acid concentration, substrate, solvent, and temperature. The enantiomeric purity of remaining substrates was identical to that of the starting substrate, indicating that the enantiomeric substrates did not undergo a ring‐opening reaction. The results provided additional evidence supporting the mechanism proposed earlier in acid‐catalyzed stereoselective heteronucleophilic and homonucleophilic substitutions and the resulting racemization of enantiomeric 3‐alkoxy‐1,4‐benzodiazepines in alcoholic solvents. © 1995 W