Angelina Flores-Parra, Patricia Suárez-Moreno, Sonia A. Sánchez-Ruíz, Margarita Tlahuextl, Javier Jaen-Gaspar, Hugo Tlahuext, Raúl Salas-Coronado, Alejandro Cruz, Heinrich Nöth, Rosalinda Contreras, Chlorination reactions of ephedrines revisited. Stereochemistry and functional groups effect on the reaction mechanisms, Tetrahedron: Asymmetry 9, 1661-1671 (1998). http://dx.doi.org/10.1016/S0957-4166(98)00155-4
The stereochemistry of the chlorination reactions with SOCl2 of free ephedrine and pseudoephedrine and their hydrochlorides, oxamides and sulfonamides was analyzed. Chlorination of free and hydrochloride erythro isomers occurs with 100% inversion of configuration at C-1 (SN2 mechanism). Chlorination of oxamides and sulfonamides of erythro isomers occurs with retention of the configuration at C-1, (SNi mechanism). Chlorination reactions in all threo isomers and derivatives hydrochlorides, oxamides or sulfonamides gave the same ratio of erythro (40%) and threo isomers (60%) (SN1 mechanism). Treatment of the isomeric mixture of the chlorodeoxyephedrine and chlorodeoxypseudoephedrine hydrochloride in DMSO with HCl changes the isomeric ratio, increasing the erythro isomer content (65%). Using the erythro ethanolamines it is possible to arrive stereoselectively at the erythro chloroamines if the compound is previously tosylated or converted to the amide, or to the threo chloroamines if the compound is directly chlorinated with SOCl2.