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

Abstract

Flash vacuum pyrolysis (FVP) of 4-acetyltetrazolo[1,5-a]pyridine 5 at 400 °C provides 3-methyl isoxazolo[3,4-b]pyridine 6 whose structure was confirmed by X-ray crystallography. At higher pyrolysis temperatures, the unstable heteroindoxyl 8 was obtained, which exists as the keto form (1,2-dihydropyrrolo[2,3-b]pyridin-3-one) 8K in CDCl(3) solution and the enol tautomer (3-hydroxypyrrolo[2,3-b]pyridine) 8E in DMSO. The heteroindoxyl 8 oxidatively dimerises to the heteroindigotin 9, undergoes condensation reactions at the 2-position and reacts with methoxymethylene Meldrum's acid at the 1-position. FVP of the corresponding acetyltetrazolo[1,5-a]quinoline 19 was much more complex, with 2-(cyanophenyl)acetonitrile 30 (rather than a heteroindoxyl) the major product at 750 °C. FVP of 3-acetyl-4-azidoquinoline 24 at 400 °C gave 3-methylisoxazolo[4,3-c]quinoline 33, but rearrangement to the heteroindoxyl was not observed at higher temperatures.

Palladium-Catalyzed Synthesis of 1H-Pyrazolo[4,3-c]quinolines and 4-Anilinoquinoline-3-carbonitriles from 4-Chloroquinoline-3-carbaldehydes

“…16 This procedure has now evolved into an efficient tool for the synthesis of quinoline derivatives, including the 2-and 4-chloroquinoline-3-carbaldehydes. 17 As previously reported, 18 4-chloroquinoline-3-carboxaldehyde (2a) was prepared in 50% yield from 1-(2-aminophenyl)ethanone (1a) by treatment with Vilsmeier's reagent at 90 °C for 12 hours. The corresponding reactions of the 4-substituted 1-(2-aminophenyl)ethanones 1b and 1c gave the 6-substituted 4-chloroquinoline-3-carboxaldehydes 2b and 2c, respectively, in comparable yields (Scheme 1).…”

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

“…Although the heteroindoxyl (8) could be reliably detected in the complex pyrolysate, it was never the major product and proved too unstable to isolate (Scheme 2). 3 In this paper, we complete our current studies of heteroindoxyls by using the nitrene strategy to achieve the successful synthesis of the benzothiophene analogue of 3, viz. 1,2-dihydro [1]benzothieno [3,2b]pyrrol-3-one (9).…”

“…We have recently employed a gas-phase nitrene insertion process to generate indoxyl (1) 1 and its heterocyclic analogues (3) 2 and (4) 3 under flash vacuum pyrolysis (FVP) conditions (Scheme 1). Azides or fused tetrazoles were used as precursors to the nitrene (e.g., 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.…”

Synthesis of 2-(trifluoromethyl)benzo[b][1,8]naphthyridin-4(1H)-one derivatives using trifluoroacetimidoyl chlorides

“…2-Chloro-3-formyl-quinolines 6a-e were synthesized from their corresponding acetanilides 5a-e according to the literature procedures [11][12][13]. Quinolinyl-alcohols 7d,e and quinolinyl-ketones 8d,e were prepared as previously reported [14,15]. Trifluoroacetimidoyl chlorides 9a-e were obtained employing the procedure described by Uneyama et al [16].…”