One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

Abstract

The development of novel and efficient synthesis methods for 2-substituted benzazole derivatives is of interest as they are biologically active substances. Herein, a simple method for the synthesis of 2-aryl- and 2-alkyl-substituted benzazoles is described. The reaction of 2-aminophenols with thioamides at 60 °C in the presence of triphenylbismuth dichloride in 1,2-dichloroethane as a promoter afforded various 2-aryl- and 2-alkylbenzoxazoles in moderate to excellent yields under mild reaction conditions. This method could also be applied to the synthesis of benzimidazoles and benzothiazoles. This study presents the first use of triphenylbismuth dichloride to produce benzimidoyl chloride from thioamides by desulfurization and chlorination, as well as its application to the synthesis of 2-substituted benzazoles.

Synthesis of Tetracyclic Benzazole–Condensed Quinazolinones through Triphenylbismuth Dichloride Assisted Cyclodesulfurization

“…A control experiment was conducted to investigate the reaction pathway and mechanism (Scheme 3). The reaction of aniline ( 9) with methyl-2-isothiocyanatobenzoate (2) gave 3-phenyl-2-thioxo-2,3-dihydroquinazolin-4-one (11), which was expected to form via thiourea 10. When 11 was treated with Ph 3 BiCl 2 under standard conditions, only disulfide 12 was isolated in 77% yield, and the desulfurized 3phenylquinazolinone 13 was not observed.…”

“…10 Moreover, the third study, published in 2022, involved the reaction of thioamides with benzimidoyl chloride, induced by the desulfurization and chlorination of thioamides and Ph 3 BiCl 2 , affording benzoxazoles. 11 Nevertheless, there are no reports on the one-pot tandem reaction of o-phenylenediamine derivatives and methyl 2-isothiocyanatobenzoate to synthesize benzazole-condensed quinazolinones using Ph 3 BiCl 2 as the cyclodesulfurization agent. Herein, we report a versatile synthesis of benzo [4,5]imidazo [2,1-b]quinazolinones via Ph 3 BiCl 2 -assisted cyclodesulfurization of 3-(2-aminophenyl)-2-thioxo-2,3dihydroquinazolin-4(1H)-one derivatives that are generated from o-phenylenediamines and 2-isothiocyanatobenzoate (Scheme 1).…”

“…Japan. Various N -Boc- o -phenylenediamine derivatives ( 1a – f ), 13 N -tosyl- o -phenylenediamine ( 1h ), 14 and Ph 3 BiCl 2 ( 4a ) 11 were prepared according to reported procedures. CCDC 2338954 ( 6a ) and 2338953 ( 8h ) contain the supplementary crystallographic data for this paper.…”

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

“…Fascinated by the immense pharmacological profiles of pyrazole, thioamide and amide derivatives, it was envisaged to develop a practical approach towards the synthesis of pyrazolethioamide and pyrazole-amide conjugates. Elemental sulfur was explored as a sulfurating reagent for the generation of thioamides owing to its nontoxic, odorless nature and versatile reactivity profile [65][66][67][68][69][70][71][72][73][74][75][76]. To the best of our knowledge, the syntheses of pyrazole C-3/4/5-linked thioamide and amide conjugates have not been reported.…”