Synlett 2018; 29(06): 810-814
DOI: 10.1055/s-0036-1591875
letter
© Georg Thieme Verlag Stuttgart · New York

Use of Phenacyl Thiosalicylates for the Preparation of 3-Hydroxybenzo[b]thiophene Derivatives

Patricia Trapani
a   Department of Organic Chemistry, Faculty of Science, Palacký University, 17. Listopadu 12, 771 46 Olomouc, Czech Republic
,
Lubomír Kvapil
a   Department of Organic Chemistry, Faculty of Science, Palacký University, 17. Listopadu 12, 771 46 Olomouc, Czech Republic
,
Pavel Hradil
a   Department of Organic Chemistry, Faculty of Science, Palacký University, 17. Listopadu 12, 771 46 Olomouc, Czech Republic
,
b   Institute of Molecular and Translation Medicine, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 5, 779 00, Olomouc, Czech Republic   Email: Miroslav.soural@upol.cz
› Author Affiliations
The authors are grateful to project CZ.1.07/2.3.00/20.0009 from the European Social Fund and internal grants from Palacký University (IGA_PrF_2017_009 and IGA_LF_2017_028). The infrastructure of this project (Institute of Molecular and Translation Medicine) was supported by the National Program of Sustainability (project LO1304).
Further Information

Publication History

Received: 03 October 2017

Accepted after revision: 27 November 2017

Publication Date:
06 February 2018 (online)


Abstract

In this work, we attempted to synthesize thioflavonols using rearrangement of phenacyl thiosalicylates prepared by two different approaches and subjected to cyclization under acidic conditions. Contrary to our expectations, the isolated products were identified as (3-hydroxybenzo[b]thiophen-2-yl)(phenyl)methanones. The detailed reaction mechanism was elucidated by characterization of all reaction intermediates with HPLC and NMR spectroscopy. The applicability of the reaction using different phenacyl esters was tested.

Supporting Information

 
  • References and Notes

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  • 20 Phenacyl ester 6a or 6b (0.48 mmol) was dissolved in neat TFA (1.5 mL), and the reaction mixture was heated to reflux for 3.5 h in a sealed vessel. After completion of reaction, the TFA was evaporated under a stream of nitrogen, and the yellow oily residue was purified by semipreparative HPLC to obtain the corresponding benzothiophene. Compound 7a: yield 80%. 1H NMR (500 MHz, CDCl3): δ = 13.45 (s, 1 H), 8.10–8.01 (m, 3 H), 7.74 (d, J = 8.2 Hz, 1 H), 7.65–7.59 (m, 1 H), 7.58–7.51 (m, 3 H), 7.44 (t, J = 7.5 Hz, 1 H) ppm.13C NMR (126 MHz, CDCl3): δ = 191.95, 165.50, 140.93, 138.37, 132.78, 130.41, 130.31, 128.86, 128.54, 124.88, 124.14, 123.11, 109.75 ppm.* HRMS (ESI-TOF): m/z calcd for C15H10O2S [M – H]: 253.0318; found: 253.0323. Compound 7b: yield 27 %. 1H NMR (500 MHz, CDCl3): δ = 13.75–13.59 (br s, 1 H), 8.13–8.08 (m, 2 H), 8.07–8.04 (m, 1 H), 7.77–7.72 (m, 1 H), 7.57–7.52 (m, 1 H), 7.46–7.40 (m, 1 H), 7.05–7.00 (m, 2 H), 3.97–3.83 (s, 3 H) ppm. 13C NMR (126 MHz, CDCl3): δ = 190.47, 165.41, 163.48, 140.58, 130.99, 130.84, 130.51, 130.11, 124.83, 124.03, 123.05, 114.17, 109.35, 55.69 ppm. HRMS (ESI-TOF): m/z calcd for C16H12O3S [M – H]: 283.0423; found: 283.0431.
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