CHLORINATION REACTIONS OF EPHEDRINES REVISITED - STEREOCHEMISTRY AND FUNCTIONAL-GROUPS EFFECT ON THE REACTION-MECHANISMS

The stereochemistry of the chlorination reactions with SOCl2 of free e phedrine and pseudoephedrine and their hydrochlorides,oxamides and sul fonamides was analyzed. Chlorination of free and hydrochloride erythro isomers occurs with 100% inversion of configuration at C-1 (S(N)2 mec hanism). Chlorination of oxamides and sulfonamides of erythro isomers occurs with retention of the configuration at C-1, (S(N)i mechanism). Chlorination reactions in all three isomers and derivatives hydrochlor ides, oxamides or sulfonamides gave the same ratio of erythro (40%) an d three isomers (60%) (S(N)1 mechanism). Treatment of the isomeric mix ture of the chlorodeoxyephedrine and chlorodeoxypseudoephedrine hydroc hloride in DMSO with HCl changes the isomeric ratio, increasing the er ythro isomer content (65%), Using the erythro ethanolamines it is poss ible to arrive stereoselectively at the erythro chloroamines if the co mpound is previously tosylated or converted to the amide, or to the th ree chloroamines if the compound is directly chlorinated with SOCl2. ( C) 1998 Elsevier Science Ltd. All rights reserved.