A Novel Synthesis of 2-Trichloromethylchromones and 7-Trichloromethylnorkhellin

Abstract

A N o v e l S y n t h e s i s o f 2 -T r i c h l o r o m e t h y l c h r o m o n e s a n d 7 -T r i c h l o r o m e t h y l n o r k h e l l i nAbstract: The reaction of 2-hydroxyacetophenones with trichloroacetyl chloride in the presence of pyridine at -30°C followed by treatment of the reaction mixture with potassium tert-butylate affords 2-hydroxy-2-trichloromethylchroman-4-ones. Dehydration then provides the 2-trichloromethyl-chromones.

Synthesis of 3-substituted 2-trifluoro(trichloro)methyl-2H-chromenes by reaction of salicylaldehydes with activated trihalomethyl alkenes

“…Although these compounds are not found in nature, their derivatives are reported to be useful from industrial and medical points of view [40,41]. These facts and our continuing interest in the chemistry of trifluoromethyl analogues of natural chromans and chromenes [19,20,25] led us to investigate the synthesis of the hitherto unknown 2-CX 3 -3-R-2H-chromenes (X = F, Cl; R = COPh, NO 2 ). In this work, we report a simple and convenient synthesis of these compounds involving the condensation of salicylaldehydes 1 with trihaloethylidene derivatives of acetophenone and nitromethane 2a-c, prepared from trifluoro(trichloro)acetaldehyde hydrates [42][43][44][45].…”

“…As a result, considerable efforts have been made in the development of trifluoromethylated analogues of precocenes [19][20][21], cromakalim [22][23][24], and lactarochromal [19,20,25], in which both or one of the methyl groups in the gem-dimethyl moiety are replaced by the CF 3 group. In spite of advances in this area, published data on the synthesis of 2-(trihalomethyl)-2H-chromenes are lacking.…”

6-Polyfluoroacyl- and 6-trichloroacetylnorkhellins: Synthesis and reaction with aromatic amines

“…It is important that trichloromethyl derivatives 2e [5] also reacted with diethoxymethyl acetate under the same reaction conditions to give 6-trichloroacetylnorkhellin 3e in 86% yield (3e:4e = 86:14 in a CDCl 3 solution). The structures of norkhellin derivatives 3a-e compare well with the results of elemental analysis, 1 H, 19 F NMR, and IR spectroscopy (Scheme 2).…”

“…The IR spectra of 5a-e showed absorption bands in the two ranges 3460-3230 and 1650-1600 cm −1 due to the OH and NH groups and the aminoenone fragment. A characteristic feature of the 1 H NMR spectra is the appearance of one singlet at δ 8.34-9.14 ppm for the OH proton (doublet with 4 3 COCl according to the described procedures [5,6].…”

“…In view of the unique biological properties displayed by khellin 1a on the one hand and by many fluorinated heterocyclic compounds [3] on the other hand, we have described recently [4][5][6] the synthesis of 7-polyfluoroalkyl-and 7-trichloromethylnorkhellins 1b,c ( Fig. 1), which are highly reactive building blocks for the preparation of new khellin derivatives with a potential biological activity [6].…”