Synlett 2015; 26(07): 931-936
DOI: 10.1055/s-0034-1380183
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Unprecedented Benzofused [1,2,4]-Triazoloquinazolines via Benzyne Diels–Alder Reaction with 7-Vinyl-[1,2,4]triazolo[1,5-c]pyrimidines as Dienes

Chao Wang
Department of Chemistry, Fudan University, Shanghai 200433, P. R. of China   Email: qrwang@fudan.edu.cn
,
Caifei Tang
Department of Chemistry, Fudan University, Shanghai 200433, P. R. of China   Email: qrwang@fudan.edu.cn
,
Xiangdong Fang
Department of Chemistry, Fudan University, Shanghai 200433, P. R. of China   Email: qrwang@fudan.edu.cn
,
Zhiming Li
Department of Chemistry, Fudan University, Shanghai 200433, P. R. of China   Email: qrwang@fudan.edu.cn
,
Quanrui Wang*
Department of Chemistry, Fudan University, Shanghai 200433, P. R. of China   Email: qrwang@fudan.edu.cn
› Author Affiliations
Further Information

Publication History

Received: 23 December 2014

Accepted after revision: 30 January 2015

Publication Date:
24 February 2015 (online)


Abstract

The benzyne Diels–Alder reaction with 7-vinyl-[1,2,4]triazolo[1,5-c]pyrimidines as a kind of unusual acyclic dienes has been investigated. The transformation proceeded smoothly in the presence of CsF to afford the unprecedented partially hydrogenated benzo[f][1,2,4]triazolo[1,5-c]quinazolines in good yields. Treatment of benzo[f][1,2,4]triazolo[1,5-c]quinazolines with DDQ provided the respective dehydroaromatization products.

Supporting Information

 
  • References and Notes

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  • 19 General Procedure for Kumada Coupling of 3a–u with Vinylmagnesium Bromide A flask charged with substrate 3 (1.0 mmol) and Pd(PPh3)2Cl2 (35 mg, 0.05 mmol) was flushed with nitrogen. Anhydrous THF (10 mL) was added by syringe, and then vinylmagnesium bromide in THF (0.7 M in THF, 1.9 mL, 1.3 mmol) was added slowly by syringe over a period of about 30 min. The whole was further refluxed until the reaction was considered complete as determined by TLC analysis. The reaction solvent was removed under reduced pressure, and the residue was purified by flash column chromatography on silica gel to provide the corresponding 7-vinyl-[1,2,4]triazolo[1,5-c]pyrimidines 4. Spectral Data of 4a White powder; yield 77%; mp 187–188 °C. 1H NMR (400 MHz, CDCl3): δ = 8.28 (d, J = 4.0 Hz, 2 H, ArH), 7.48 (s, 3 H, ArH), 7.35 (s, 1 H, ArH), 6.75 (dd, J = 10.4, 16.8 Hz, 1 H, CH), 6.45 (d, J = 16.8 Hz, 1 H, CH2), 5.59 (d, J = 10.4 Hz, 1 H, CH2), 3.01 (s, 3 H, CH3). 13C NMR (100 MHz, CDCl3): δ = 165.3, 153.7, 150.8, 150.1, 134.5, 130.7, 130.3, 128.8, 127.7, 121.2, 106.0, 20.0. IR (KBr): νmax = 3061, 3016, 1626, 1543, 1459, 1428, 1321, 1287, 1216, 925, 714, 690 cm–1. ESI-HRMS: m/z calcd for C14H12N4 [M + H]+: 237.1140; found: 237.1143.
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  • 24 General Procedure for the Benzyne DA Cycloaddition of 7-Vinyl-[1,2,4]triazolo[1,5-c]pyrimidines 4a–k (Table 2) To the flask charged with a heterocyclic diene 4 (0.5 mmol), CsF (0.46 g, 3.0 mmol,) and o-(trimethylsilyl)phenyl triflate (5a, 0.45 g, 1.5 mmol) was carefully added degassed dry 1,4-dioxane (12 mL). The mixture was heated under reflux until complete consumption of the starting material (TLC monitoring – the time required was as indicated in Table 2). Concentration of the reaction mixture in vacuum followed by flash column chromatography over SiO2 (hexane–EtOAc = 1:5) afforded 7ak. Spectral Data of 7a (Table 2, Entry 1) Yellow powder; yield 76%; mp 164–165 °C. 1H NMR (400 MHz, CDCl3): δ = 9.09 (d, J = 8.0 Hz, 1 H, ArH), 8.42 (d, J = 6.8 Hz, 2 H, ArH), 7.53–7.43 (m, 4 H, ArH), 7.35–7.28 (m, 2 H, ArH), 3.13–3.05 (m, 7 H, 2 CH2, CH3). 13C NMR (100 MHz, CDCl3): δ = 165.2, 152.2, 151.1, 148.3, 136.0, 130.6, 130.5, 129.7, 128.8, 128.6, 128.1, 127.9, 127.8, 127.2, 115.6, 30.5, 28.2, 20.1. IR (KBr): νmax = 3061, 2944, 1614, 1599, 1576, 1533, 1484, 1457, 1433, 1333, 1278, 1246, 713, 687 cm–1. ESI-HRMS: m/z calcd for C20H16N4 [M + H]+: 313.1453; found: 313.1449.
  • 25 CCDC-1036102 contains the supplementary crystallographic data for this compound. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/data_request/cif. See also the Supporting Information.
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  • 27 See also Supporting Information for computation details.
  • 28 General Procedure for the Benzyne DA Cycloaddition of 7-Vinyl-[1,2,4]triazolo[1,5-c]pyrimidines 4n–u To the flask charged with 4 (1.0 mmol), CsF (0.91 g, 6.0 mmol), and o-(trimethylsilyl)phenyl triflate 5 (2.0 mmol) was carefully added degassed anhydrous MeCN (10 mL). The mixture was heated under reflux until complete consumption of the starting material (TLC monitoring). Concentration of the reaction mixture in vacuum followed by flash column chromatography over SiO2 (hexane–EtOAc, 10:1) afforded 7ny (Table 2). Spectral Data of 7n (Table 3, Entry 1) White solid; yield 56%; mp 155–156 °C. 1H NMR (400 MHz, CDCl3): δ = 9.19 (d, J = 7.8 Hz, 1 H), 8.80–8.71 (m, 2 H), 8.51–8.41 (m, 2 H), 7.64–7.60 (m, 3 H), 7.56–7.50 (m, 3 H), 7.47 (dd, J = 7.1, 0.8 Hz, 1 H), 7.38–7.33 (m, 1 H), 7.31 (d, J = 7.4 Hz, 1 H), 3.24 (t, J = 7.5 Hz, 2 H), 3.12 (t, J = 7.5 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ = 165.2, 152.5, 152.4, 146.5, 136.3, 131.7, 131.6, 130.6, 130.4, 129.8, 128.8, 128.7, 128.4, 128.0, 127.8, 127.2, 115.9, 30.7, 28.3. ESI-HRMS: m/z calcd for C25H18N4 [M + H]+: 375.1610; found: 375.1605.
  • 29 Procedure for the DDQ-Mediated Dehydrogenation of 7b and 7n 7,8-Dihydrobenzo[f][1,2,4]triazolo[1,5-c]quinazoline 7b or 7n (0.3 mmol) and DDQ (136 mg, 0.6 mmol) were dissolved in CH2Cl2 (10 mL). The mixture was heated under reflux until complete consumption of the starting material (TLC monitoring). After filtration and removal of the solvent, the residue was purified by the flash column chromatography on SiO2 with hexane–EtOAc (10:1) as eluent to afford, respectively, the dehydrogenated benzo[f][1,2,4]triazolo[1,5-c]quinazolines 8a and 8b. Spectral Data of 8a White solid; yield 90%; mp 177–178 °C. 1H NMR (400 MHz, CDCl3): δ = 10.17 (d, J = 8.5 Hz, 1 H), 8.31–8.14 (m, 2 H), 8.06–7.98 (m, 2 H), 7.93–7.83 (m, 1 H), 7.79–7.68 (m, 1 H), 7.66–7.55 (m, 1 H), 7.52–7.42 (m, 2 H), 3.20 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 150.9, 148.1, 144.8, 143.29, 133.7, 133.1, 132.4, 132.1, 131.1, 131.0, 129.8, 129.7, 128.5, 128.3, 127.9, 127.5, 126.9, 126.1, 113.1, 20.2. ESI-HRMS: m/z calcd for C20H13ClN4 [M + H]+: 345.0907; found: 345.0886. Spectral Data of 8b White solid; yield 60%; mp 192–193 °C. 1H NMR (400 MHz, CDCl3): δ = 10.32 (d, J = 8.4 Hz, 1 H), 8.82–8.70 (m, 2 H), 8.60–8.45 (m, 2 H), 8.19 (d, J = 8.9 Hz, 1 H), 8.11 (d, J = 8.9 Hz, 1 H), 8.03 (d, J = 7.9 Hz, 1 H), 7.96–7.86 (m, 1 H), 7.80–7.71 (m, 1 H), 7.69–7.63 (m, 3 H), 7.61–7.51 (m, 3 H).13C NMR (100 MHz, CDCl3): δ = 156.1, 153.0, 146.7, 143.6, 133.2, 132.5, 132.1, 131.7, 130.8, 130.7, 128.9, 128.6, 128.5, 128.3, 128.1, 127.7, 126.8, 113.2, 107.0, 103.5, 101.9. ESI-HRMS: m/z calcd for C25H16N4 [M + H]+: 373.1453; found: 373.1440.