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Synlett 2019; 30(09): 1053-1056
DOI: 10.1055/s-0037-1611817
DOI: 10.1055/s-0037-1611817
letter
New Facile Synthesis of 3,4-Dihydroquinazoline-2(1H)-thiones by a Sequential Ugi-Azide/Staudinger/Aza-Wittig/Cyclization Reaction
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.
Key words
3,4-dihydroquinazoline-2(1H)-thione - Ugi-azide reaction - methyldiphenylphosphane - aza-Wittig reaction - cyclization reactionSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1611817.
- Supporting Information
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References and Notes
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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.