Syntesis and reactivity of 1-bromomethyl-5-oxo-4-phenyl-1,2,4,5,6,7,8,9-octahydrobenzo[4,5]thieno[3,2-e][1,3]oxazolo[3,2-a]-pyrimidin-11-ium bromides

Abstract

We demonstrated formerly that the N 1 -nucleophilic center of unsaturated thio ethers of thieno[2,3-d]pyrimidine could be brought into reactions of electrophilic heterocyclization [1,2]. The further study of bromination conditions of 2-hydroxy-4-oxo-3-phenylthieno[2,3d]pyrimidine allyl ether (I) revealed that notwithstanding the ratio and concentration of initial reagents and the time of the reaction the bromination of compound I in acetic acid gave rise to a fused system of salts of benzothienooxazolopyrimidinium II and III of angular structure.The bromination of allyl ether I followed by storage of the reaction mixture for 5 days at the use of low concentration of ether I (0.51.0%) and at the ratio of the initial compounds ether Ibromine equal to 1:1 (or 1:2) gave as a result monobromide II. In the event that the bromoheterocyclization is carried out at high concentration of ether I (5.010.0%) and at the ratio of the initial compounds ether Ibromine equal to 1:4 for 34 h the reaction yields tribromide III. We showed also that monobromide II formed at stirring tribromide III for 1 h in acetone or butanone. The direct bromination of salt II afforded tribromide III in a quantitative yield. In the 1 H NMR spectra of salts II and III lack the signals from the allyl fragment of initial ether I, and the resonances of a spin system ABX characteristic of the formed oxazolinium ring appear for monobromide II and tribromide III respectively as follows: a multiplet of the methine proton at 4.85 and 4.84 ppm; two doublet of 6 1 1 2 2 &+ +& &+ 6 1 1 2 2 &%U + %U B ,, , 6 1 1 2 2 &+&+ 2+ &+ %U 6 1 1 2 2 &+ %U B ,,, &+ &221D %U ,9 &+ &221D %U %U

The Use of Electrophilic Cyclization for the Preparation of Condensed Heterocycles

“…Regardless of the substrate, higher yields of the target salts were achieved by using a solution of the halogen (2-3 equiv) in acetic acid at room temperature (Scheme 1). More recently, the high regioselectivity of the oxazoline ring closure in the allyl ether of thieno [2,3-d]pyrimidine 1 under similar conditions was reported 18 (Scheme 1). Chemical transformation of the obtained tricyclic salts under the action of an O-nucleophile leads to cleavage of the annulated thiazoline (oxazoline) and formation of unsaturated heteroaryl-substituted mercaptans (alcohols) 4 with promising bioactivity.…”

[1,3]Thiazolo[2′,3′:3,4][1,2,4]triazolo[1,5‐a]pyrimidines – A New Heterocyclic System Accessed via Bromocyclization

“…Considering these observations, it was envisaged to synthesize a new tricycle system by introducing an additional ring to [1,3]thiazolo[1,2,4]triazole. In recent years, heteroannulation processes based on electrophilic halocyclization has proved to be useful in producing various heterocycles: furane , pyrrole , selenophene , pyrazole , piperazine , indole , quinoline , imidazothiazole , imidazotriazine , and thiazolo(oxazolo‐)thienopyrimidine . For example, [1,3]thiazolo[1,2,4]triazoles formation was reported to be due to electrophilic heterocyclization of monoalkenyl‐substituted [1,2,4]triazolethiones affected by halogens and mineral acids .…”