Recrystallization-induced tautomerism and selective imine formation of N-diphenylmethylene-serine methyl ester

Diphenylmethylene serine methyl ester is an important precursor for the synthesis of O-glycoprotein mimics; however, it exists as an equilibrium mixture of imine and oxazolidine forms due to intramolecular cyclization. Upon crystallization from ether/hexane, the oxazolidine form is typically obtained as the predominant species, and the pure imine form has not been isolated to date. In this study, diphenylmethylene serine methyl ester was synthesized from serine methyl ester and benzophenone imine, purified by chromatography, and subsequently recrystallized from methanol to selectively afford the imine form in high purity. The structure was confirmed by nuclear magnetic resonance spectroscopy and single-crystal X-ray diffraction analysis. Tautomeric interconversion was investigated in deuterated chloroform at various temperatures, revealing a gradual conversion of the imine into the oxazolidine form until equilibrium was established. These findings clarify the tautomeric behavior of this compound and provide an effective strategy for the selective isolation of tautomers of serine derivatives.