Reactions of Some Nitrogen Heterocycles with Chlorodifluoromethane under Conditions of Phase‐Transfer Catalysis.

Abstract

2006 N-Alkylation O 0268 Reactions of Some Nitrogen Heterocycles with Chlorodifluoromethane under Conditions of Phase-Transfer Catalysis. -A simple synthetic procedure for the N-difluoromethylation of various N-heterocycles is developed. -(JONCZYK*, A.; NAWROT, E.; KISIELEWSKI, M.; J. Fluorine Chem. 126 (2005) 11-12, 1587-1591; Fac. Chem., Warsaw Univ. Technol., PL-00-662 Warszawa, Pol.; Eng.) -R. Staver 13-056

New N-difluoromethylindoles: features of N-difluoromethylation of indoles with electron-donor or electron-withdrawing substituents

“…The products 2a-e cannot be separated from the initial indoles 1a-e by fractional distillation, or crystallization with heating, because in these cases their decomposition occurs. Earlier, other researches failed to isolate compound 2c [7]. The desired product was detected in the reaction mixture, but it was stated that this compound is insufficiently stable for isolation either by column chromatography or distillation.…”

“…However, N-difluoromethylation of indoles has been studied insufficiently till now. Despite the fact that the first N-difluoromethylation of indole derivative was performed long ago in 1961, to obtain N-difluoromethylindole-2-carboxylic acid ethyl ester [6], difluoromethylation of unsubstituted indole was carried out only in 2005 with chlorodifluoromethane (Freon-22) under phase-transfer catalysis [7,8]. The further information about such compounds is meager and has random character.…”

“…The further information about such compounds is meager and has random character. This is partially due to the fact that some indole derivatives with difluoromethyl group at nitrogen atom are very sensitive to the traces of acid, and their autocatalytic decomposition occurs during storage [7]. So far, the N-difluoromethyl derivatives of indole with donor substituents only have not been described.…”

Synthesis and Reactions of Five-Membered Heterocycles Using Phase Transfer Catalyst (PTC) Techniques

“…Alkylation of indole 217, 2,3-dimethylindole 218 with chlorodifluromethane under liquid-liquid technique (CH 2 Cl 2 /aq. NaOH/BzTEACl) afforded the corresponding 1-alkylated derivatives 219 and 220, respectively [74] ( Figure 82). Barraja et al heated 2-substituted-3-bromoindoles 221 with excess of different nucleophiles, solid KOH, and dibenzo-18-crown as a phase transfer catalyst to afford the corresponding 3-substituted indoles 222 in a satisfactory increase of yield [75] (Figure 83).…”

“…Pyrazole, imidazole, 1, 2, 4-triazole, indazole, benzotriazole NO Br-(CH 2 ) n -Br = Me, PhCH 2 , CH 2 CH = CH 2 , X = Br, Iof benzotriazole 267 with chlorodifluromethane under liquid-liquid conditions (CH 2 Cl 2 /aq. NaOH/ BzTEACl) has afforded 1-(difluoromethyl)-1H-benzotriazole 270[74] (Figure 100). Reaction of 4-substituted-1,2,3-triazol 271 with alkyl bromide 272 under basic condition using PTC Bu 4 NBr produced N-substituted 1,2,3-triazole derivatives 273a-c [93] (Figure 101).…”