Synthesis and Chemistry of 4,5-Dihydrothieno[3,2-b]pyrrol-6-one—A Heteroindoxyl

Abstract

Flash vacuum pyrolysis (FVP) of 2-acetyl-3-azidothiophene gives 3-methylthieno[3,2-c]isoxazole as the major product at a furnace temperature of 350 degrees C whereas at temperatures above 550 degrees C the new heteroindoxyl 4,5-dihydrothieno[3,2-b]pyrrol-6-one is exclusively formed. The heteroindoxyl exists predominantly as the keto tautomer. It is O-protonated by TFA, N-acetylated by acetic anhydride, N-nitrosated by nitrous acid, and provides an N-methylene Meldrum's acid derivative on treatment with methoxymethylene Meldrum's acid. Reactions of 4,5-dihydrothieno[3,2-b]pyrrol-6-one with diazonium salts, with isatin, and with dimethyl acetylenedicarboxylate take place at the methylene position to provide a hydrazone, an indirubin analogue, and a succinate derivative, respectively. Oxidation of 4,5-dihydrothieno[3,2-b]pyrrol-6-one gives a heteroindigotin, which shows a hypsochromic shift in the UV spectrum, relative to indigotin itself.

Flash vacuum pyrolysis of 2-acetyl-3-azido[1]benzothiophene

“…By comparison, indoxyl itself is present as the enol form (1E) almost exclusively (>95%) in DMSO, whereas the thiophene analogue (3) shows an unexpected preference for the keto form (3K) (80%) in the same solvent. 2…”

“…Azides or fused tetrazoles were used as precursors to the nitrene (e.g., 2). [1][2][3] Because of the easy oxidative dimerisation of these products to indigotin (5) (and its heterocyclic analogues) such reactions are excellent examples of the synthetic advantages of FVP with the monomeric products conveniently generated under vacuum in a solventfree, air-free environment.…”

3-Hydroxypyrrolo[2,3-b]pyridine and related compounds – indoxyl analogues with fused electron deficient rings

“…Despite the wealth of information that is available on indigotin 1 1 and its reduced monomer, indoxyl 2, 2 the first example of a heteroindoxyl, in which the benzene ring is replaced by a heterocycle, was reported by our group in 2009. 3 This compound, 4,5dihydrothieno [3,2-b]pyrrol-6-one 3, has an electron rich thiophene ring as the fused heterocycle. The synthetic strategy involved generation of an arylnitrene intermediate under flash vacuum pyrolysis (FVP) conditions, and its subsequent insertion into a CH bond of an adjacent acetyl group; 3 the method proved to be applicable to the preparation of indoxyl 2 itself.…”

Synthesis of Thioethers Using Triethylamine-Activated Phosphorus Decasulfide (P4S10)

“…18 The first nucleophilic displacement of halogens located on heterocycles (pyrizadines) by sulfur was performed by Castle and Kaji with P 4 S 10 , leading to the formation of the corresponding thiols. 19 Thiols have also been obtained by using hydrosulfide-exchange resin, 20 sodium hydrosulfide hydrate, 21 and H 2 S. 22 In this work, P 4 S 10 was used to obtain thioethers via nucleophilic displacement reactions of halogens (Br) under milder conditions and in shorter reaction times. The effects of carbonyl, aromatic/heteroaromatic, and alkyl subunits were investigated.…”