Reactions of 6‐thiotheophylline with alkylating agents and epichlorohydrin: Isolation of S‐alkylated 6‐thiotheophylline and 7‐(2,3‐thioepoxypropyl)theophylline

Abstract

Alkylation of 6‐thiotheophylline (1) under the aprotic basic condition affords S‐alkylated 6‐thiotheophylline (3) together with an N7 ‐alkylated product 4. There is a tendency that the more reactive the alkylating agents are, the higher the yields of S‐alkylated products are. On the other hand, treatment of 6‐thiotheophylline (1) with epichlorohydrin afforded an unexpected product, 7‐(2,3‐thioepoxypropyl)theophylline (6), neither an S‐alkylated compound 3g nor an N7 ‐alkylated compound 4g. The chemical structure was determined by nmr spectroscopic analysis.

Stereoselective synthesis of 4H-3,1-benzothiazines via tandem nucleophilic addition/epoxy ring-opening cyclization reactions of 2-(3-phenyloxiranyl)phenyl isothiocyanates

“…Thus, the present rearrangement would proceed intramolecularly in a pathway, as shown in Scheme 6 (19). The rearrangement would be initiated by the nucleophilic attack by the hydroxy group to the isothiourea-carbon in 6, followed by the intramolecular S N 2-type O-ring-opening-S-ring-closing reaction by the thiolate to produce thiiranes 8 having both inverted stereogenic carbon centers.…”