Condensation of 2-hydroxyacetophenones with trichloroacetonitrile as a route to 2-trichloromethylchromones and 4-hydroxycoumarins

Abstract

Condensation of 2-hydroxyacetophenones with [richloroacetonitrile in the presence of Nmethylanilinomagnesium bromide affords hydroxyary'l [}-amino-l~-trichloromethylvinyl ketones, which are converted into 2-trichloromethylchromones upon treatment with concentrated HCI. rite restllting compounds react with alcoholic solutions of NH-, or KOH to form 3-amino-I-( 2-hydrowaryl)-4,4,4-trichlorobut-2-en-f -ones and 4-hydroxycoumarins, respecti,~elv.Key ~ords: 2-hydroxyacetophenones, trichloroacetonitrile, 3-amino-1-(2-hydroxya~'l)-4.4,4-trichlorobut-2-en-l-ones. 2-trichloromethylchromones, 4-hydroxycoumarins.Previously, ! we have described condensation of 2-hydroxyacetophenone with trichloroacctonitrile in the presence of PhN(EttMgBr, which proceeded through formation of 3-amino-l-t2-hydroxyphenyl)-4,4.4-trichtorobut-2-en-l-one (la) to yield 2-trichloromethylchromone ~'2a). 2-Trichloromethylbenzo[h]chromone. z 2-trichloromethylbenzo[t]chromone. 2 and 5,7-dimethyl-2-trichloromethylctaromone 3 were synthesized analogously. The reactions of 2-methylchromone and 7-hydroxy-2-methylchromone with thionyl chloride in boiling benzene afforded chmmone 2a and 7-chloro-2-trichloromethylchromone, respectively. These compounds gave 4-hydroxycoumarin (3ai and 7-chloro-4-hydroxycoumarin, respectively, in low yields upon treatment with alcoholic alkali. 4 Recently, we have demonstraled that 2-trichloromethylchromones reacted with ethylene-and trimethylenediamines in alcoholic solutions at room temperature to form 2-(2-hydroxyaroylmethylene)imidazolidines s and 2-(2-hydroxyaroylmethylene)hexahydropyrimidines. 6 Owing to the high reactivity of 2-trichloromethylchromones, which is manifested in the ia.cl that both the opening of the pyrone ring and the replacement of the trichloromethyl group proceed readily under the action of diainines, these compounds can be considered as synthetic equivalents of difficultly accessible trichloropropynyl ketones and as very attractive initial reagents tot preparing partially hydrogenated hcterocycles.Other data on the synthesis and properties of 2-trichloromethylchromones are lacking in the literature. Apparently, this is associated with the fact that trichloroacelic esters unde~o halolbrm-type cleavage under conditions of Claisen condensation with the use of sodium alkoxides to form chloroform 7 and dichlorocarbene. S This fact was confirmed by the results of the study, 9 which demonstrated that condensation of methyl dichlorofluoroacetate with acetophenone in the presence of MeONa gave the target product in low yield due to the formation of chlorofluorocarbene, as well as by the fact that ethyl trichloroacetate undergoes haloform-type cleavage even under the action of seconda~' amines. I~ In this connection, condensation of 2-hydroxyacetophenone with trichloroacetonitrile t instead of alkyl trichloroacetates is a ve~ promising procedure for the synthesis of chromones containing tile labile trichloromcthyl substituent at position 2.in the present work, we extended this procedure to substituted 2-hydroxy...

Synthesis and antimicrobial activities of some novel bis-pyrazole derivatives containing a hydrophosphoryl unit

“…The oxidation reaction of compound 6 with selenium dioxide in dry dioxane yielded bis{chromeno [4,3-c]pyrazol-4-oxo-2-yl}phosphine oxide (7) (Scheme 7). The absorption band of carbonyl groupappeared at 1652 cm -1 [34,35] in the IR spectrum of 7. Also, its structure was confirmed from 1 H NMR spectrum by disappearance of OH and C2-H protons of compound 6.…”

“…Abdel-Aziz et al / European Journal of Chemistry 2 (1) (2011)[25][26][27][28][29][30][31][32][33][34][35] …”

Synthesis of Chromeno[4,3‐b]pyrrol‐4(1H)‐ones, from β‐Nitroalkenes and 4‐Phenylaminocoumarins, under Solvent–free Conditions

“…The required 4‐phenylaminocoumarin derivatives 3a–c (R= H, 8Me, and 6Cl, respectively) were synthesized by reaction of aniline with the corresponding 4‐hydroxycoumarins ( 2a–c , R= H, 8Me, and 6Cl, respectively),– under microwave irradiation.…”

A Novel Synthesis of 2-Trichloromethylchromones and 7-Trichloromethylnorkhellin

“…1 We showed that these compounds can be obtained by the condensation of 2-hydroxyacetophenones with trichloroacetonitrile in the presence of N-methylanilinomagnesium bromide followed by acid hydrolysis of the aminoenones. [2][3][4][5] In several cases, formation of aminoenones was accompanied by considerable polymerization of the reaction mixture, impeding the isolation of target products. Till date, this reaction was the only method for obtaining 2-trichloromethylchromones in moderate yields because the Claisen condensation usually used for synthesis of chromones gives unsatisfactory results in the case of trichloroacetic acid esters due to side reactions associated with haloformic splitting 6 and formation of dichlorocarbene.…”