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Synlett 2018; 29(12): 1583-1588
DOI: 10.1055/s-0037-1610147
letter
© Georg Thieme Verlag Stuttgart · New York

Reaction between Chalcones, 1,3-Dicarbonyl Compounds, and Elemental Sulfur: A One-Pot Three-Component Synthesis of Substituted Thiophenes

Mehdi Adib*
a   School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran   Email: madib@khayam.ut.ac.ir
,
Saideh Rajai-Daryasarei
a   School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran   Email: madib@khayam.ut.ac.ir
,
Rahim Pashazadeh
a   School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran   Email: madib@khayam.ut.ac.ir
,
Mehdi Jahani
a   School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran   Email: madib@khayam.ut.ac.ir
,
Massoud Amanlou
b   Pharmaceutical Sciences Research Center and Department of Medicinal Chemistry, Tehran University of Medical Sciences, Tehran, Iran
› Author Affiliations
Further Information

Publication History

Received: 22 February 2018

Accepted after revision: 19 April 2018

Publication Date:
05 June 2018 (online)

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Abstract

A simple and atom-economic synthesis of highly substituted thiophenes is demonstrated. Heating a solution of a chalcone and a ­linear/cyclic 1,3-dicarbonyl compound with elemental sulfur in CH3CN in the presence of NEt3 at 80 °C afforded the corresponding substituted thiophenes in good to excellent yields.

Key words

multi-component reactions - substituted thiophenes - ­sulfur - chalcones - 1,3-dicarbonyl compounds

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610147.
  • Supporting Information
 

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  • 14 Representative Procedure for the Synthesis of 3-Acetyl-4-benzoyl-2-methyl-3-phenyl thiophene (4a) A mixture of 1,3-diphenyl-2-propen-1-one (1a) (0.208 g, 1.0 mmol), 2,4-pentanedione (2a) (0.100 g, 1.0 mmol), and triethylamine (0.025 g 0.25 mmol) in CH3CN (1 mL) was stirred at 80 °C for 12 h. Subsequently, triethylamine (0.071 g, 0.7 mmol) and elemental sulfur (0.038 g, 1.2 mmol) were added to the mixture, which was heated to 80 °C for a further 5 h. After completion of the reaction, as indicated by TLC monitoring, the mixture was cooled to ambient temperature and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography by using n-hexane/EtOAc (8:1 v/v) as the eluent to afford the desired product 4a. 3-Acetyl-5-benzoyl-2-methyl-4-phenylthiophene (4a) White solid. Yield: 0.269 g, 84%. Mp 60–62 °C. IR (KBr) (ν max/cm–1): 1682 and 1622 (C=O), 1520, 1488, 1445, 1363, 1301, 1234, 1171, 1113, 1073, 1028, 963, 904, 869, 786, 721, 696, 656, 621. EI-MS: m/z (%) = 320 (100) [M]+, 305 (33), 277 (8), 243 (7), 227 (30), 215 (7), 201 (19), 171 (19), 121 (11), 105 (78), 77 (67), 43 (21). 1H NMR (500.1 MHz, CDCl3): δ = 1.80 (s, 3 H, CH3), 2.60 (s, 3 H, CH3), 7.09–7.16 (m, 7 H, 7 CH), 7.30 (t, 1 H, J = 7.4 Hz, CH), 7.50 (dd, 2 H, J = 8.2, 1.2 Hz, 2 CH) ppm. 13C NMR (125.8 MHz, CDCl3): δ = 15.36 and 31.21 (2 CH3), 127.95 (2 CH), 128.39 (CH), 128.42 (2 CH), 129.53 (2 CH), 129.79 (2 CH), 132. 36 (C H), 135.03, 135.32, 137.77, 141.40, 145.04 and 148.29 (6 C), 189.84 and 199.80 (2 C=O) ppm. Anal. Calcd for C20H16O2S (320.41): C, 74.97; H, 5.03; S, 10.01. Found: C, 74.83; H, 4.86; S, 10.13.