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25 July 2014

6-Chloro-2-hydroxy-2-trifluoromethyl-2H-chromene-3-carboxylic acid (5-allylsulfanyl-[1,3,4]thiadiazol-2-yl)-amide

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School of Science, Henan Agricultural University, Zhengzhou 450002, China
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Author to whom correspondence should be addressed.
Molbank2014, 2014(3), M830;https://doi.org/10.3390/M830
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Abstract

A new chromene containing 1,3,4-thiadiazole and trifluoromethyl(CF3), 6-chloro-2-hydroxy-2-trifluoromethyl-2H-chromene-3-carboxylic acid (5-allylsulfanyl-[1,3,4]thiadiazol-2-yl)-amide was synthesized and its structure was characterized by IR, 1H-NMR, 13C-NMR, 19F-NMR and HRMS.

1. Introduction

Many compounds containing chromene ring moiety display broad spectrum of biological activity [,,,]. 2H-Chromenes have gained much attention because of various biological activities such as antiviral, anti-tumor, anti-bacterial, fungicidal, antiflamatory, antioxidative and activator of potassium channels effects [,,,,]. Recently, introduction of fluorine atoms into organic compounds has been regarded as one of the best ways for the enhancement or modification of their original biological activities [,]. It was found and verified that the trifluoromethyl(CF3) group, regarded as a pseudo-halogen, imparted unique biological activity [,].
On the other hand, thiadiazoles are organic heterocyclic compounds having been reported to have a wide application in pharmaceuticals and pesticides due to their good and extensive biological activities [,,]. Introduction of a thiadiazole ring into the chromene may improve the biological activities. As a continuation of our previous work for synthesis of heterocyclic compounds with chromene skeleton [,,], we report here another new 2H-chromene, 6-chloro-2-hydroxy-2-trifluoromethyl-2H-chromene-3-carboxylic acid (5-allylsulfanyl-[1,3,4]thiadiazol-2-yl)-amide, and it was fully characterized.

Synthesis

The title compound 3 was prepared from dehydration of 6-chloro-2-hydroxy-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid 2, obtained by hydrolysis of ethyl 6-chloro-2-hydroxy-2-(trifluoromethyl)-2H-chromene-3-carboxylate 4 [], with an equimolar amount of 5-allylsulfanyl-[1,3,4]thiadiazol-2-ylamine 1 in acetonitrile for 24 h in the presence of N,N,N′,N′-tetramethyluranium-O-(benzotriazol-1-yl)tetrafluoroborate (TBTU) and triethyl amine. This new chromene was fully characterized by IR, 1H-NMR, 13C-NMR and HRMS data. As shown in Scheme 1.
Scheme 1. The synthesis of 6-chloro-2-hydroxy-2-trifluoromethyl-2H-chromene-3-carboxylic acid (5-allylsulfanyl-[1,3,4]thiadiazol-2-yl)-amide, 3.

Experimental

All reagents were purchased from commercial sources and used without further purification. Infrared spectra were recorded with a Nicolet IS10 Fourier Transform Infrared Spectrophotometer (4000–400 cm−1) (KBr pellets). 1H and 13C-NMR spectra of CDCl3 solutions were obtained by a Bruker DPX-400 Spectrometer, respectively. 19F-NMR spectra were recorded in CDCl3 by instrument calibration. High resolution mass spectrometry data were measured on a Waters Q-Tof micro™ instrument with an electrospray ionization source (ESIMS). Melting points were determined on an X-5 digital microscopic melting-point apparatus (Beijing Tech Instruments Co., Beijing, China) and are uncorrected.
To a solution of 6-chloro-2-hydroxy-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid (2) (2.20 g, 7.5 mmol) and 5-allylsulfanyl-[1,3,4]thiadiazol-2-ylamine (1) (1.30 g, 7.5 mmol), in dry acetonitrile (100 mL), TBTU (4.81 g, 15 mmol) and Et3N (3.1 mL, 22.5 mmol) were added. The mixture was stirred for 24 h at 40 °C with TLC monitoring using ethyl acetate: ethylene dichloride (1:1) as eluent. After completion of the reaction, the solvent was removed by reduced pressure distillation. The residue was chromatographed on silica gel using ethyl acetate:ethylene dichloride (1:3~1:1) as the eluent, to make the title compound 3 a white solid.
Yield: 56%; m.p.: 205.2~206.1 °C.
IR, (ν, cm−1): 3457 (-OH), 3128 (N-H), 1654 (C=O), 1611, 1563, 1488 (Ar), 1281 (C-N), 1186 (C-O-C).
1H-NMR (CDCl3, 400 MHz): δ 4.00 (d, J = 6.4 Hz, 2H, CH2S), 5.36 (d, J = 10 Hz, 1H, -CH=), 5.53 (d, J = 16.8 Hz, 1H, Allyl-H), 5.97–6.08 (m, 2H, Allyl-H, Ar-H), 7.11 (d, J = 8.8 Hz, 1H, Ar-H), 7.45 (d, J = 7.6 Hz, Ar-H), 8.64 (s, 1H, H-4).
13C-NMR (CDCl3, 100 MHz): δ 36.00, 69.95(q, 2JC, F = 33.5 Hz, CCF3), 105.14, 114.50, 119.03, 120.96, 123.45(q, 1JC, F = 286.6 Hz, CF3), 127.57, 128.28, 130.14, 133.95, 138.64, 153.85, 158.25, 163.33, 164.73.
19F-NMR (CDCl3, 376.5 MHz): −76.68 (-CF3).
HRMS: calcd for m/z (C16H11ClF3N3O3S2-OH)+: 431.9855; found: 431.9854.

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3Supplementary File 4

Acknowledgments

We are grateful for the financial support of this work from Key Science and Technique Foundation of Henan Province (112101110200).

Conflicts of Interest

The authors declare no conflict of interest.

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