Synlett 2019; 30(09): 1053-1056
DOI: 10.1055/s-0037-1611817
letter
© Georg Thieme Verlag Stuttgart · New York

New Facile Synthesis of 3,4-Dihydroquinazoline-2(1H)-thiones by a Sequential Ugi-Azide/Staudinger/Aza-Wittig/Cyclization Reaction

Jun Xiong*
a   School of Pharmacy, Hubei University of Science and Technology, Xianning 437100, Hubei, P. R. of China
b   Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Hubei International Scientific and Technological Cooperation Base of Pesticide and Green Synthesis, Central China Normal University, Wuhan 430079, P. R. of China   Email: xjhbust@163.com   Email: mwding@mail.ccnu.edu.cn
,
Qing Min
a   School of Pharmacy, Hubei University of Science and Technology, Xianning 437100, Hubei, P. R. of China
,
Gang Yao
a   School of Pharmacy, Hubei University of Science and Technology, Xianning 437100, Hubei, P. R. of China
,
Jia-An Zhang
a   School of Pharmacy, Hubei University of Science and Technology, Xianning 437100, Hubei, P. R. of China
,
Hai-Feng Yu
a   School of Pharmacy, Hubei University of Science and Technology, Xianning 437100, Hubei, P. R. of China
,
b   Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Hubei International Scientific and Technological Cooperation Base of Pesticide and Green Synthesis, Central China Normal University, Wuhan 430079, P. R. of China   Email: xjhbust@163.com   Email: mwding@mail.ccnu.edu.cn
› Author Affiliations
This research was funded by the National Natural Science Foundation of China (No. 21572075), the Doctoral Research Fund of Hubei University of Science and Technology (BK201808) and the Hubei University of Science and Technology Pharmacy Key Discipline Foundation (2019-20YZ13).
Further Information

Publication History

Received: 04 April 2019

Accepted after revision: 12 April 2019

Publication Date:
07 May 2019 (online)


Abstract

A new facile synthesis of 3,4-dihydroquinazoline-2(1H)-thiones by an Ugi-azide/Staudinger/aza-Wittig/cyclization sequence has been developed. The Ugi-azide reactions of 2-azidobenzaldehydes, amines, trimethylsilyl azide, and isocyanides produced tetrazoles, which, when treated with methyldiphenylphosphane and CS2, produced 3,4-dihydroquinazoline-2(1H)-thiones in good overall yields via a sequential Staudinger/aza-Wittig/cyclization reaction.

Supporting Information

 
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  • 26 Preparation of Ugi Intermediates 5; General Procedure: A mixture of 2-azidobenzaldehyde 1 (2 mmol), amine 2 (2 mmol), trimethylsilyl azide 3 (2 mmol), and isocyanide 4 (2 mmol) was stirred in methanol (10 mL) at room temperature for 12–24 h. After the reaction was complete, the precipitate was filtered to give 5 (when R2 is an aryl group) or the solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel (ether/petroleum ether = 1:4, v/v) to give 5 (when R2 is an alkyl group).
  • 27 Compound 5n: Yellow solid (88%); mp 201–203 °C. 1H NMR (CDCl3, 600 MHz): δ = 7.45–6.54 (m, 7 H, Ar-H), 6.26 (d, J = 9.6 Hz, 1 H, CH), 4.49 (d, J = 8.4 Hz, 1 H, NH), 2.22 (s, 3 H, CH3), 1.76 (s, 9 H, 3 CH3). 13C NMR (CDCl3, 150 MHz): δ = 154.3, 142.6, 138.6, 135.2, 130.0, 129.8, 128.8, 127.8, 125.7, 118.3, 114.1, 62.1, 48.3, 29.9, 20.4. HRMS (ESI): m/z [C19H21ClN8+H]+ calcd: 397.1650; found: 397.1655.
  • 28 Preparation of 3,4-Dihydroquinazoline-2(1H)-thiones 8; General Procedure: To the azide 5 (1 mmol) in anhydrous toluene (5 mL) was added dropwise Ph2PCH3 (0.20 g, 1 mmol) in toluene (5 mL) at room temperature. The mixture was stirred at r.t. for 0.5 h to form iminophosphorane 6 (TLC monitoring). CS2 (0.15 g, 2 mmol) was then added and the solution was heated to 110 °C for 4–6 h, After the reaction was complete, the precipitate was filtered to give 3,4-dihydroquinazoline-2(1H)-thione 8.
  • 29 Compound 8a: White solid (yield: 86%); mp 257–258 °C. 1H NMR (DMSO-d 6, 600 MHz): δ = 11.40 (s, 1 H, NH), 7.33–7.07 (m, 9 H, Ar-H), 6.99 (s, 1 H, CH), 1.34 (s, 9 H, 3 CH3). 13C NMR (DMSO-d 6, 150 MHz): δ = 175.7, 155.9, 143.7, 134.1, 129.6, 129.4, 128.2, 126.1, 123.2, 118.6, 114.9, 62.6, 56.4, 29.6. HRMS (ESI): m/z [C19H20N6S+H]+ calcd: 365.1543; found: 365.1545.