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Synlett 2015; 26(02): 177-182
DOI: 10.1055/s-0034-1378928
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© Georg Thieme Verlag Stuttgart · New York

A One-Pot, Three-Component Synthesis of 3-(1H-Pyrazol-1-yl)-4H,7H-[1,2,4,5]tetraazino[6,1-b][1,3]benzoxazin-7-ones under Solvent-Free Conditions

Mehdi Adib*
a   School of Chemistry, College of Science, University of Tehran, P. O. Box 14155-6455 Tehran, Iran   Fax: +98(21)66495291   Email: madib@khayam.ut.ac.ir
,
Mehdi Soheilizad
a   School of Chemistry, College of Science, University of Tehran, P. O. Box 14155-6455 Tehran, Iran   Fax: +98(21)66495291   Email: madib@khayam.ut.ac.ir
,
Long-Guan Zhu
b   Chemistry Department, Zhejiang University, Hangzhou 310027, P. R. of China
,
Jing Wu
b   Chemistry Department, Zhejiang University, Hangzhou 310027, P. R. of China
› Author Affiliations
Further Information

Publication History

Received: 17 August 2014

Accepted after revision: 13 October 2014

Publication Date:
14 November 2014 (online)

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Abstract

A one-pot, three-component synthesis of 3-(1H-pyrazol-1-yl)-4H,7H-[1,2,4,5]tetraazino[6,1-b][1,3]benzoxazin-7-ones is described which involves heating a mixture of 1,2-dihydro-3,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,2,4,5-tetrazine, aldehydes, and dimedone in the presence of a catalytic amount of p-toluenesulfonic acid under solvent-free conditions. The bridgehead-fused 6:6:6 systems with one ring-junction nitrogen atom were obtained in excellent yields.

Key words

[1,2,4,5]tetraazino[6,1-b][1,3]benzoxazin-7-ones - 1,2-dihydro-3,6-bis(1H-pyrazol-1-yl)-1,2,4,5-tetrazine - solvent-free reaction - multicomponent reactions - cyclizations - heterocycles

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034-1378928.
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  • References and Notes

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  • 15 Typical Procedure for the Preparation of Compounds 8a–kA mixture of DHBPTz (0.272 g, 1.0 mmol), benzaldehyde (0.127 g, 1.2 mmol), dimedone (0.140 g, 1.0 mmol) and PTSA (0.052 g, 0.3 mmol) was heated at 120 °C for the time indicated in Table 1. After completion of the reaction as indicated by TLC monitoring, the reaction mixture was cooled to r.t., and the residue was purified by column chromatography using n-hexane–EtOAc (5:1) as eluent. The solvent was removed and the pure product 8a was obtained.3-(3,5-Dimethyl-1H-pyrazol-1-yl)-9,9-dimethyl-6-phenyl-6,8,9,10-tetrahydro-4H,7H-[1,2,4,5]tetraazino[6,1-b][1,3]-benzoxazin-7-one (8a)Yield 0.372 g (92%); yellow powder; mp 167 °C. IR (KBr): 3255 and 3144 (NH), 1709 (C=O), 1642 (C=N), 1601, 1491, 1370, 1318, 1270, 1219, 1113, 1028, 971, 911, 773, 744 cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 1.04 and 1.05 (2 × s, 6 H, 2 × CH3), 1.83 (s, 2 H, CH2), 2.21 (d, 2 J = 16.5 Hz, 1 H, CH CCHD), 2.28 (d, 2 J = 16.5 Hz, 1 H, CHCCH D), 2.31 and 2.40 (2 × s, 6 H, 2 × CH3), 6.08 (s, 1 H, pyrazole CH), 6.42 (s, 1 H, NCH), 7.31 (t, J = 7.5 Hz, 1 H, CH), 7.39 (t, J = 7.5 Hz, 2 H, 2 × CH), 7.53 (d, J = 7.5 Hz, 2 H, 2 × CH), 7.95 (s, 1 H, NH). 13C NMR (125.8 MHz, CDCl3): δ = 11.9 and 13.7 (2 × pyrazole CH3), 28.4 and 28.6 [C(CH3)2], 34.6 (CH2C=C), 34.7 [C(CH3)2], 50.8 (CH2C=O), 64.0 (NCH), 109.7 (pyrazole CH), 114.0 (C), 127.1, 128.2 and 128.7 (3 × CH), 135.8, 139.2, 143.0, 150.2, 152.5 and 157.8 (6 × C), 191.5 (C=O). MS: m/z (%) = 404 (58) [M+], 368 (6), 339 (6), 327 (100), 243 (25), 227 (36), 202 (10), 179 (23), 163 (22), 149 (36), 122 (20), 95 (32), 77 (32). Anal. Calcd (%)for C22H24N6O2 (404.47): C, 65.33; H, 5.98; N, 20.78. Found: C, 65.30; H, 6.05; N, 20.72.6-(4-Chlorophenyl)-3-(3,5-dimethyl-1H-pyrazol-1-yl)-9,9-dimethyl-6,8,9,10-tetrahydro-4H,7H-[1,2,4,5]tetraazino-­[6,1-b][1,3]benzoxazin-7-one (8e)Yield 0.404 g (92%); yellow powder; mp 207 °C. IR (KBr): 3220 and 3124 (NH), 1695 (C=O), 1648 (C=N), 1593, 1492, 1458, 1370, 1321, 1272, 1220, 1115, 1087, 1018, 970, 909, 831, 791, 743, 680 cm–1. 1H NMR (400.1 MHz, CDCl3): δ = 0.99 and 1.00 (2 × s, 6 H, 2 × CH3), 1.79 (d, 2 J = 17.3 Hz, 1 H, CH ACHB), 1.80 (d, 2 J = 17.3 Hz, 1 H, CHACH B), 2.18 (d, 2 J = 16.4 Hz, 1 H, CH CCHD), 2.23 (d, 2 J = 16.4 Hz, 1 H, CHCCH D), 2.28 and 2.35 (2 × s, 6 H, 2 × CH3), 6.05 (s, 1 H, pyrazole CH), 6.36 (s, 1 H, NCH), 7.31 (d, J = 8.8 Hz, 2 H, 2 × CH), 7.45 (d, J = 8.8 Hz, 2 H, 2 × CH), 8.51 (s, 1 H, NH). 13C NMR (100.6 MHz, CDCl3): δ = 11.9 and 13.6 (2 × pyrazole CH3), 28.2 and 28.6 [C(CH3)2], 34.6 (CH2C=C), 34.7 [C(CH3)2], 50.7 (CH2C=O), 63.3 (NCH), 109.7 (pyrazole CH), 113.5 (C), 128.5 and 128.8 (4 × CH), 133.9, 135.6, 137.9, 143.1, 150.5, 152.6 and 157.8 (7 × C), 191.6 (C=O). MS: m/z (%) = 440 (20) [M+, 37Cl], 438 (65) [M+, 35Cl], 353 (2), 342 (4), 327 (100), 271 (5), 243 (42), 179 (30), 163 (45), 95 (28), 67 (18), 55 (17). Anal. Calcd (%) for C22H23ClN6O2 (438.92): C, 60.20; H, 5.28; N, 19.15. Found: C, 60.18; H, 5.32; N, 19.11.3-(3,5-Dimethyl-1H-pyrazol-1-yl)-9,9-dimethyl-6-propyl-6,8,9,10-tetrahydro-4H,7H-[1,2,4,5]tetraazino[6,1-b][1,3]benzoxazin-7-one (8k)Yield 0.322 g (87%); yellow powder; mp 189 °C. IR (KBr): 3237 (NH), 1713 (C=O), 1670 (C=N), 1628, 1593, 1493, 1439, 1382, 1323, 1279, 1223, 1134, 1110, 1085, 1028, 970, 934, 904, 850, 814, 773, 716, 670 cm–1. 1H NMR (400.1 MHz, CDCl3): δ = 0.96 (t, J = 7.3 Hz, 3 H, CH2CH 3), 0.98 and 1.01 (2 × s, 6 H, 2 × CH3), 1.40–1.51 (m, 2 H, CH2), 1.62 (d, J = 17.4 Hz, 1 H, CH ACHB), 1.63–1.71 (m, 1 H, CH), 1.72 (d, J = 17.4 Hz, 1 H, CHACH B), 1.81–1.88 (m, 1 H, CH), 2.18 (d, J = 16.3 Hz, 1 H, CH CCHD), 2.24 (d, J = 16.3 Hz, 1 H, CHCCH D), 2.27 and 2.36 (2 × s, 6 H, 2 × CH3), 5.37 (br d, J = 6.3 Hz, 1 H, NCHCH2), 6.04 (s, 1 H, pyrazole CH), 7.55 (s, 1 H, NH). 13C NMR (100.6 MHz, CDCl3): δ = 11.8, 13.6 and 13.8 (2 × pyrazole CH3 and CH2 CH3), 18.3 (CH2CH3), 28.1 and 28.7 [C(CH3)2], 34.4 (CH2C=C), 34.5 [C(CH3)2], 36.2 (CHCH2), 50.8 (CH2C=O), 62.3 (NCH), 109.6 (pyrazole CH), 113.9, 135.8, 142.9, 150.5, 152.4 and 158.6 (6 × C), 191.7 (C=O). MS: m/z (%) = 370 (5) [M+], 327 (100), 273 (3), 243 (22), 163 (20), 95 (12), 67 (8), 55 (7). Anal. Calcd (%) for C19H26N6O2 (370.45): C, 61.60; H, 7.07; N, 22.69. Found: C, 61.51; H, 6.93; N, 22.57.