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

Abstract

This paper is dedicated to Professor Juzo Nakayama on the occasion of his 65th birthday and retirement.Tandem nucleophilic addition/epoxy ring-opening cyclization reactions of 2-(3-phenyloxiranyl)phenyl isothiocyanates to produce 4-hydroxy(phenyl)methyl-4H -3,1-benzothiazines were investigated. In the reactions, carbon, sulfur, nitrogen, and oxygen nucleophiles were introduced at the 2-position of the benzothiazines, together with the two adjacent stereogenic centers arising from the epoxy carbon centers. We also found an interesting stereospecific rearrangement of 2-(alkylamino)-4-hydroxy(phenyl)methyl-4H -3,1-benzothiazines to 1-alkyl-3-(2-(trans-3-phenylthiiran-2-yl)-phenyl)urea.

Synthesis and Anticancer Activity of New 2‐Aryl‐4H‐3,1‐benzothiazines

“…Moreover, various isothiocyanates have been used as starting materials to obtain this heterocycle through other cyclization processes 11–17. Based on the rearrangement of 2‐isothiocyano triarylmethanes in the presence of AlCl 3 Abaev and co‐workers synthesized 2,4‐diaryl‐4 H ‐3,1‐benzothiazines 12.…”

“…An aryl ring is found to migrate to the carbon atom of an isothiocyano group followed by intramolecular cyclization as a result of an electrophilic attack of the benzhydryl carbocation on the sulfur atom. Tandem nucleophilic addition/epoxy ring‐opening cyclization reactions of 2‐(3‐phenyloxiranyl)phenyl isothiocyanates to produce 4‐hydroxy(phenyl)methyl‐4 H ‐3,1‐benzothiazines were investigated by Otani and others 17.…”

A facile and effective procedure for the synthesis of new 1,3-thiazine-2-thione derivatives

“…[11][12][13][14][15] The majority of the reactions between carbon disulfide and N-nucleophiles involve the addition of carbon disulfide to N−H bonds. [16] The products of these reactions, dithiocarbamate salts, reacts with epoxides, [17][18][19] 2-chloro-1,3-dicarbonyl compounds, [20] chloroacetic acid, [21] diethyl 2-chloromalonate, [22] bromoacetophenone, [23] ethyl bromopyruvate, [24] α-haloketones, [25] 3,4-dihydro-2H-pyran, [26] electron-deficient alkenes, [27] β-nitrostyrene derivatives, [28] dibenzoylacetylene, [29] quinines, [30] and itaconic anhydride [31] that can be transformed into dithiocarbamate derivatives. *Corresponding author.…”