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Short Note

(E)-3-Methyl-6-(3-oxo-3-(thiophen-2-yl)-1-propenyl)-2(3H)-benzothiazolone

1
Department of Plant Pathology and Chemistry, Faculty of Ecology and Landscape Architecture, University of Forestry, 10 Kliment Ohridsky Blvd., Sofia 1756, Bulgaria
2
Department of Pharmaceutical and Applied Organic Chemistry, Faculty of Chemistry and Pharmacy, Sofia University St. Kliment Ohridski, 1 James Bourchier Blvd., Sofia 1164, Bulgaria
*
Author to whom correspondence should be addressed.
Molbank 2016, 2016(2), M897; https://doi.org/10.3390/M897
Submission received: 1 March 2016 / Revised: 1 April 2016 / Accepted: 5 April 2016 / Published: 15 April 2016

Abstract

:
The title compound, (E)-3-methyl-6-(3-oxo-3-(thiophen-2-yl)-1-propenyl)-2(3H)-benzothiazolone, was synthesized by Claisen-Schmidt condensation of 3-methyl-2(3H)-benzothiazolone-6-carbaldehyde with 2-acetylthiophene in 94% yield. The structure of the target compound was confirmed using 1H-NMR, 13C-NMR, IR, MS, and elemental analysis.

Graphical Abstract

1. Introduction

Chalcones, being quite good pharmacophores for the design of new bioactive molecules, have received increasing attention from medicinal chemists during the past decade. Compounds with chalcone fragments can be found in some natural products as well as in synthetic derivatives with antitumour [1], antibacterial [2], antioxidant [3] and antiulcer [4] activities.
In continuation of our previous studies on the synthesis of heterocyclic chalcone derivatives with benzoxazolone [5] or benzothiazolone ring [6,7,8], in this work we report the preparation of a novel (E)-3-methyl-6-(3-oxo-3-(thiophen-2-yl)-1-propenyl)-2(3H)-benzothiazolone. The compound consists of thiophene and benzothiazolone heterocycles, connected via α,β-unsaturated carbonyl system, a key framework of chalcones.

2. Results

The synthesis of (E)-3-methyl-6-(3-oxo-3-(thiophen-2-yl)-1-propenyl)-2(3H)-benzothiazolone (3) (Scheme 1) was performed by a Claisen-Schmidt condensation of 3-methyl-2(3H)-benzothiazolone-6-carbaldehyde (1) with 2-acetylthiophene (2). The reaction was carried out in ethanol in the presence of aqueous KOH and led to only one product with nearly quantitative yield.
The structure of compound 3 was confirmed by 1H- and 13C-NMR, IR, MS and elemental analysis and all data are in accordance with the assumed structure. The lactam and ketone C=O stretching bands in IR spectra were seen at about 1640 cm−1 and 1670 cm−1. In particular, analysis of 1H-NMR spectra revealed that the structure is geometrically pure with the E configuration, as derived from coupling constant J = 15.4 Hz for vinyl protons (Figure S1).

3. Experimental Section

3.1. General Information

All chemicals were purchased from Acros Organics (Geel, Belgium). 3-Methyl-2(3H)-benzothiazolone-6-carbaldehyde (1) was synthesized as described previously [9]. Reactions were monitored by thin-layer chromatography (TLC) on silica gel plates (Kieselgel 60 F254) using hexane/acetone (2:1 v/v) as eluent. The purity of the final compound was determined by GC-MS on an Agilent 6890 system with MSD 5973 (single quadrupol and EI at 70 eV ionization), (Wilmington, DE, USA), using a capillary column HP-5/MS (30 m × 0.250 mm × 0.25 µm). Carrier gas He was used at 0.8 mL/min. The temperature programmed mode was used (from 60 °C for 2 min, then with 10 °C/min to 300 °C for 10 min). The sample was introduced in splitless injection mode.
Melting point was determined on a Boetius hot-stage microscope (Carl Zeiss Jena, Germany) and was uncorrected. IR spectrum (nujol) was recorded on a Specord 71 spectrometer (Carl Zeiss Jena, Germany). NMR spectra were recorded in DMSO-d6 on a Bruker Avance III HD 500 (Bruker BioSpin GmbH, Rheinstetten, Germany), operating at 500 MHz for 1H and at 125.8 MHz for 13C. Chemical shifts are given in parts per million (δ) relative to the solvent peak. Coupling constants (J) were measured in hertz (Hz). The elemental analyses was carried on a VARIO EL III Elemental analyzer (Elementar Analysensysteme GmbH, Hanau, Germany) and the results for C, H, and N were within ±0.4% of the theoretical values.

3.2. Synthesis of (E)-3-Methyl-6-(3-oxo-3-(thiophen-2-yl)-1-propenyl)-2(3H)-benzothiazolone (3)

To a slightly heated solution of 3-methyl-2(3H)-benzothiazolone-6-carbaldehyde (1, 386 mg, 2 mmol) in ethanol (5 mL), 2-acetylthiophene (2, 278 mg, 2.2 mmol) was added, followed by 10% aq. KOH (1 mL). The obtained mixture was stirred for 24 h at room temperature to afford a precipitate. The crystalline product was filtered, washed with cold ethanol, water to neutrality and dried.
Yellow crystals. Yield: 94% (566 mg), m.p.: 205–207 °C (2-methoxyethanol). IR (nujol): 1643, 1671 (C=O) cm−1. 1H-NMR (500 MHz, DMSO-d6): δ (ppm) 3.42 (s, 3H, CH3), 7.31 (dd, 1H, thiophene-H, J = 3.8 Hz, J = 4.9 Hz), 7.37 (d, 1H, arom. H, J = 8.4 Hz), 7.71 (d, 1H, =CHCO, J = 15.5 Hz), 7.84 (d, 1H, ArCH=, J = 15.5 Hz), 7.88 (dd, 1H, arom. H, J = 8.4 Hz, J = 1.6 Hz), 8.05 (dd, 1H, thiophene-H, J = 4.9 Hz, J = 0.9 Hz), 8.21 (d, 1H, arom. H, J = 1.5 Hz), 8.29 (dd, 1H, thiophene-H, J = 3.8 Hz, J = 0.9 Hz). 13C-NMR (125.8 MHz, DMSO-d6): δ (ppm) 29.2, 111.6, 120.8, 122.1, 122.6, 128.2, 128.9, 129.9, 133.4, 135.4, 139.4, 142.5, 145.6, 168.7, 181.3. Anal. calcd. for C15H11NO2S2 (301.36): C, 59.78; H, 3.68; N 4.65. Found: C, 59.41; H, 3.79; N, 4.72. MS (EI): [M]+ m/z = 301(100), [M + 2]+ m/z = 303(11), 272(19), 240(18), 218(11), 165(17), 160(16), 111(52).

Supplementary Materials

Supplementary File 1Supplementary File 2Supplementary File 3Supplementary File 4
Copies of the 1H-, 13C-NMR and MS spectra for compound 3 are available online at https://www.mdpi.com/1422-8599/2016/2/M897.

Acknowledgments

The authors are thankful to the University of Forestry, Sofia, Bulgaria for the financial support.

Author Contributions

O.P. designed the whole experiments; Y.I. and M.G. performed the experiments and contributed to manuscript; O.P. and Y.I. analyzed the NMR spectral data and wrote the manuscript; C.C. provided the mass spectra. All authors read and approved the final manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

References

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Scheme 1. Synthesis of (E)-3-methyl-6-(3-oxo-3-(thiophen-2-yl)-1-propenyl)-2(3H)-benzothiazolone (3).
Scheme 1. Synthesis of (E)-3-methyl-6-(3-oxo-3-(thiophen-2-yl)-1-propenyl)-2(3H)-benzothiazolone (3).
Molbank 2016 m897 sch001

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MDPI and ACS Style

Ivanova, Y.; Gerova, M.; Chanev, C.; Petrov, O. (E)-3-Methyl-6-(3-oxo-3-(thiophen-2-yl)-1-propenyl)-2(3H)-benzothiazolone. Molbank 2016, 2016, M897. https://doi.org/10.3390/M897

AMA Style

Ivanova Y, Gerova M, Chanev C, Petrov O. (E)-3-Methyl-6-(3-oxo-3-(thiophen-2-yl)-1-propenyl)-2(3H)-benzothiazolone. Molbank. 2016; 2016(2):M897. https://doi.org/10.3390/M897

Chicago/Turabian Style

Ivanova, Yordanka, Mariana Gerova, Christo Chanev, and Ognyan Petrov. 2016. "(E)-3-Methyl-6-(3-oxo-3-(thiophen-2-yl)-1-propenyl)-2(3H)-benzothiazolone" Molbank 2016, no. 2: M897. https://doi.org/10.3390/M897

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