Reactivity of chlorodeoxypseudoephedrines with oxo-, thio-, and selenocyanates

Herein, the reactivity of chlorodeoxypseudoephedrine hydrochlorides with oxo-, thio-, and selenocyanate nucleophiles is reported. 1,3-Heterazolidine-2-iminium or ammonium salts were obtained stereoselectively in most cases. The hard–soft nature of the calcogen atom determines the mechanistic pathway via an SN2 (X = O), aziridine intermediate (X = Se), or both (X = S). A simple method to synthesize stereoselectively the trans-isomer of 3,4-dimethyl-5-phenyl-oxazolidine-2-iminium chloride and the cis-isomer of 4-methyl-5-phenyl-oxazoline-2-ammonium chloride, was also found. In addition, heterazolidine-2-imines or amines were liberated from the corresponding salts [Cl− or XCN− (X = O, S, Se)] with aqueous NaOH. Finally, cis-3,4-dimethyl-5-phenyl-oxazolidine-2-iminium chloride, cis-4-methyl-5-phenyl-oxazoline-2-amine, and trans-4-methyl-5-phenyl-selenazoline-2-amine compounds were studied by X-ray diffraction.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

(1S,2R)-(−)-cis-3,4-Dimethyl-5-phenyl-oxazolidine-2-iminium chlorideC11H15N2OCl[α]D24=-15.0 (c 2.0 × 10−4 g/mL, methanol)Source of chirality: (1S,2R)-(+)-ephedrine

(1R,2R)-(−)-trans-3,4-Dimethyl-5-phenyl-oxazolidine-2-iminium chlorideC11H15N2OCl[α]D24=-15.0 (c 2.0 × 10−4 g/mL, methanol)Source of chirality: (1S,2R)-(+)-ephedrine

(1S,2R)-(−)-cis-3,4-Dimethyl-5-phenyl-oxazolidine-2-imineC11H14N2O[α]D24=-120.0 (c 2.0 × 10−4 g/mL, chloroform)Source of chirality: (1S,2R)-(−)-ephedrine

(1R,2R)-(−)-trans-3,4-Dimethyl-5-phenyl-oxazolidine-2-imineC11H14N2O[α]D24=-5.0 (c 2.04 × 10−4 g/mL, chloroform)Source of chirality: (1S,2R)-(−)-ephedrine

(1R,2R)-(−)-(2-Chloro-1-methyl-2-phenyl-ethyl)-ureaC10H13N2OCl[α]D24=-45.0 (c 2.02 × 10−4 g/mL, methanol)Source of chirality: (1S,2R)-(+)-norephedrine

(1S,2R)-(−)-cis-4-Methyl-5-phenyl-oxazoline-2-amineC10H12N2O[α]D24=-200.0 (c 2.0 × 10−4 g/mL, chloroform)Source of chirality: (1S,2R)-(+)-norephedrine

(1S,2R)-(−)-cis-4-Methyl-5-phenyl-thiazoline-2-amineC10H12N2S[α]D24=-75.0 (c 2.04 × 10−4 g/mL, chloroform)Source of chirality: (1S,2R)-(+)-norephedrine

(1S,2S)-(−)-trans-4-Methyl-5-phenyl-selenazoline-2-amineC10H12N2Se[α]D24=-120.0 (c 2.0 × 10−4 g/mL, chloroform)Source of chirality: (1R,2S)-(−)-norephedrine