How Reaction Conditions May Influence the Regioselectivity in the Synthesis of 2,3-Dihydro-1,4-benzoxathiine Derivatives

Abstract

The exploration of different reaction conditions aiming to obtain both 2,3-dihydro-1,4benzoxathiine-2-yl derivatives and 2,3-dihydro-1,4-benzoxathiine-3-yl ones is here reported. The treatment of 1,2-mercaptophenol with an organic base and a specific 2-bromo acrylate results in a solvent-and substrate-dependent exclusive solvation of O-and S-anions, thus managing the regioselectivity.

Chlorinated Solvents: Their Advantages, Disadvantages, and Alternatives in Organic and Medicinal Chemistry

“…The environmental, health, and safety aspects of modern developments in conducting electrophilic bromination are thoroughly discussed by Eissen et al Solvents employed for electrophilic alkene bromination using Br 2 are predominantly chlorinated solvents in the following order (most occurrences): chloroform, CCl 4 , and DCM . Examples employing non-chlorinated solvents do exist such as the dibromination of methyl acrylate in acetone (89% yield using 1 equiv of Br 2 ) …”

Benzamide Derivatives Targeting the Cell Division Protein FtsZ: Modifications of the Linker and the Benzodioxane Scaffold and Their Effects on Antimicrobial Activity

“…Scheme 1 shows the synthetic pathway of benzoxathiane derivatives 1 and 3, together with the derived sulfones 2 and 4. The benzoxathiane ring was achieved by treating the 1,2-mercaptophenol in a mixture of acetonitrile (ACN) and water (1/1) [24], in the presence of ethyl 2,3-dibromopropionate, prepared as reported in literature [25], with triethylamine (TEA) as a base.…”

“…Intermediate 19 was also used to obtain 7 (see Scheme 4). The pathway was very similar to the one described for 6, but we used catechol instead of 1,2-mercaptophenol, accomplishing benzodioxane 23, which underwent reduction (24), mesylation (25) and condensation with 2,6difluoro-3-hydroxy-benzamide to afford 7. Our initial idea to obtain 8 was the application of the synthetic pathway of 6, while starting from commercial 4-pentenoic acid and catechol.…”

Resolution via diastereomeric amides of enantiopure 1,4‐benzoxathian‐2‐ and 3‐carboxylic acids and determination of their configuration

“…In that case, we resulted in achieving the pure 1,4-benzoxathian-3-carboxylamide. 12 As a result, we treated the 2-hydroxythiophenol with (S)-2,3-dibromo-1-phenylethyl propanamide in a mixture of ACN/water because the use of pure water did not let to the complete solubilization of the two reactants. Nevertheless, we fortunately resulted in obtaining the two diastereomeric amides, exclusively of the 3-regioisomer.…”