1,3-Heterazolidines-2-heterounsaturated compounds derived from ephedrines

Herein, a direct and easy method for preparing 2-oxo-, 2-thione- or 2-imine-1,3-heterazolidines derived from ephedrines and norephedrines are reported. The method is based on solvent free heating of ephedrines with oxocyanate or thiocyanate salts (180–200 °C). In the reactions with potassium oxocyanate in refluxing ethanol, it was possible to isolate ureidic derivatives. The structure and stereochemistry of the compounds were determined by 1H, 13C NMR, IR spectroscopies and mass spectrometry. Ureidic derivatives, cis-1,5-dimethyl-4-phenyl-imidazolidine-2-thione and trans-4-methyl-5-phenyl-thiazolidine-2-one are new compounds. Ephedrineurea, cis-1,5-dimethyl-4-phenyl-imidazolidine-2-thione and trans-4-methyl-5-phenyl-thiazolidine-2-one were also studied by X-ray diffraction.

Graphical abstractEphedrines 1a,b-(e,t) with potassium cyanate in refluxing ethanol, produce ephedrineureas 2a,b-(e,t). When ephedrines 1a,b-(e,t) are heated with ammonium thiocyanate under solvent free conditions, they produce thiazolidine-2-imine hydrothiocyanate 4a-t, imidazolidinethione 5a-c, thiazolidinone 8b-t and thiazolidine-2-amine hydrothiocyanate 4b-c in 40–50% yield.Figure optionsDownload full-size imageDownload as PowerPoint slide

(1S,2R)-(+)-(2-Hydroxy-1-methyl-2-phenyl-ethyl)-ureaC10H14N2O2[α]D24=+3.0 (c 1.68, EtOH)Source of chirality: (1S,2R)-(+)-norephedrine

(1R,2R)-(−)-(2-Hydroxy-1-methyl-2-phenyl-ethyl)-ureaC10H14N2O2[α]D24=-6.1 (c 1.64, EtOH)Source of chirality: (1R,2R)-(−)-norpseudoephedrine