M. Y. Hamadi, Rajni Gupta, R. Gupta
1998
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0
Influential Citations
3
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Journal
Heterocyclic Communications
Abstract
l-Chloro-3-fluorophenothiazines have been prepared by Smiles rearrangement of 3-chloro-5-fluoro-2-formamido-2'-nitrophenylsulfides in alcoholic potassium hydroxide solution. The formyl derivatives were prepared by the formylation of the resultant diphenyulsulfides obtained by the condensation of 2-amino-3-chloro-5fluorobenzenethiol with o-halonitrobenzenes in ethanolic acetate solution. 9-Chloro-7floronitrophenothiazines have been prepared by the condensation of 2-amino-3-chloro5-fluorobenzenethiol with o-halonitrobenzenes containing nitro group (s) or one nitro and halogen atom at both ortho positions to the reactive halogen atom in ethanolic sodium hydroxide solution where Smiles rearrangement occures in situ. Introduction Phenothiazines possess a wide spectrum of pharmacological and biological activities and their several derivatives are in clinical use (1). A slight alteration in the substitution pattern in phenothiazines nucleus causes a marked difference in their biological activities. Recently great interest has arisen in the anticancer activities of phenothiazines (2-8). It is considerd worthwhile to synthesize the title compounds in our research programms to develop better medicinal agents . Experimental Melting points of the synthesized compounds are uncorrected. Their purity has been checked by thin layer chromatography. Characterization of the synthesized compounds was done by their spectral data. The infrared spectra were recorded on Nicolet-Magna FT IR spectrophotometer model 550 in KBr discs. NMR Spectra were recorded at 90 MHz on Jeol FX 90Q FT NMR spectrometer in DMSO-d6 using TMS as an internal standard. F NMR Spectra were recorded with respect to hexafluorobenzene with F signal at -162.900 ppm. 1. Preparation of 2-amino-3-chloro-5-fluoro-2'-nitro-4'-substituted diphenylsulfides (4a,b) To a refluxing solution of 2-amino-3-chloro-5-fluorobenzenethiol 1 in ethanol (20 ml) and anhydrous sodium acetate in (5 ml) ethanol, an alcoholic solution of 2-halonitrobenzenes 2 in ethanol (12 ml) was added and refluxed for 3 hrs. The reaction mixture was concentrated and cooled overnight in an ice chamber. The solid separated out was filtered, washed with 30% ethanol and crystallized from methanol (Scheme-1). Physical data of the synthesized compounds (4a,b) are recorded in Table-1. Their IR data are recorded in Table-2. Vol. 4, No. 3, 1998 Synthesis of Fluorophenothiazines By Smiles Rearrangement Table-1 : Physical data Compound Molecular M.P. Yield % C, H, Ν Formula °C % Found Found Found (Calcd.) (Calcd.) (Calcd.) 4a C12H8N2O2FCIS 68 23.9 9.37 (9.38) 4b C13H8N2O4FCIS 98 33.4 8.20 (8.17) 5a C13H8N2O3FCIS 72 71.5 8.58 (8.57) 5b C14HgN205FClS 110 53.5 7.53 (7.55) 6a C)2H7NC1FS 123 78.7 57.28 2.77 5.57 (57.25) (2.78) (5.56) 6b CI3H7NCIFO2S 134 21.3 52.76 2.35 4.72 (52.79) (2.36) (4.73) 7a CI2H5CI2FN2O2S 114-115 63.5 43.52 1.50 8.47 (43.50) (1.51) (8.46) 7b C12H5CIFN3O4S 78 68.8 42.18 1.45 12.28 (42.16) (1.46) (12.29) 7c C]2H5CI2FN2O2S 117 32.2 43.52 1.50 8.45 (43.50) (1.51) (8.46) Table-2 : Infrared data Compound NHZ NH NO2 c=o C-Cl C-F 4a 349