A versatile new synthesis of quinolines and related fused pyridines, Part 5. The synthesis of 2-chloroquinoline-3-carbaldehydes

Abstract

Acetanilides are converted into 2-chloroquinoline-3-carbaldehydes in good yield by the action of Vilsmeier's reagent in phosphoryl chloride solution. The reaction is shown to involve successive conversion of the acetanilide into an imidoyl chloride and then an N-(or-chloroviny1)aniline. The latter enamine is diformylated at its P-position and subsequently cyclised to the chloroquinolinecarbaldehyde. The diformylated intermediates may be isolated in several cases and separately cyclised with polyphosphoric acid. * n.d. = not determined.

Efficient syntheses of 1,3-unsubstituted 1H-pyrazolo[3,4-b]quinolines

“…29 Reaction of 1a with hydrazine produced a hydrazone which could not be cyclised by refluxing in ethanol. We concluded that the hydrazone had E geometry and thus was sterically prevented from attacking the quinoline C-2.…”

“…In particular, and partly because of the ready availability of 2-chloro-3-formylquinolines from Meth-Cohn's convenient and efficient synthesis of such molecules from acetanilides and the Vilsmeier reagent, 29 most work has involved these chloro-aldehydes, though these are easily converted into corresponding ketones by Grignard addition then oxidation of the resulting alcohol. 24,30 The reaction of such ketones with hydrazine or arylhydrazines produces 3-substituted 1H-pyrazolo [3,4-b]quinolines simply by refluxing in methanol (Scheme 3); 24,30 it was suggested 30 that the size of the ketone substituent favours formation of the Z-stereoisomer of a first-formed hydrazone, thus having the geometry required for a subsequent ring-closing displacement of the chloride.…”

“…All the 2-chloro-3-formylquinolines (1a-f) were prepared by the Meth-Cohn method. 29 Melting points were recorded on a Philip Harris C4954718 apparatus and are uncorrected. 1 H and 13 C NMR spectra were recorded on a Bruker Avance AQS 300 MHz spectrometer, at 300 MHz and 75 MHz respectively.…”

One pot synthesis of some new 2-hydrazino-[1,3,4]thiadiazepino[7,6-b]quinolines under microwave irradiation conditions

“…Hence, in continuation of research work on developing new quinoline containing heterocycles due to their significant biological activities, it appeared expedient to synthesize a series of condensed and appropriately funtionalised 2-hydrazino[1,3,4]thiadiazepino [7,6-b]quinolines in the present study. The starting compound 2-chloro-3-formyl quinolines, (1a-h) were prepared according to the literature method 29 The 2-hydrazino-[1,3,4]thiadiazepino [7,6-b]quinoline (2a-h) were obtained in one pot by the cyclisation of 2-chloro-3-formylquinolines with carbidimide in presence of p-TsOH catalyst and DMF under microwave irradiation in good yields. This method provides high yield of products in 5-6 min making it a useful method for the synthesis of condensed thiadiazepino quinolines.…”

In-Vitro Antibacterial / Antifungal Screening of 2-Chloroquinoline Scaffold Derivatives

“…The chlorination of compounds (11,12) with SOCl 2 in dry benzene afforded intermediates 3-(chloromethyl)-2-chloroquinoline (17,18) and their successive nucleophilic substitution reaction with sulphanilamide or p-aminophenol in absolute ethanol in the presence of organic base triethylamine (TEA) gave 2-chloroquinolinyl amines (19)(20)(21)(22). While various 1 H-benzimidazol-2-ylsulfanyl)methyl (23)(24)(25)(26) derivatives were prepared by reacting intermediate (17,18) with 2-mercaptobenzimidazole or 2-mercapto-6-nitrobenzimidazole in ethanol in presence of base NaOH.…”