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Synlett 2013; 24(2): 165-168
DOI: 10.1055/s-0032-1317951
letter
© Georg Thieme Verlag Stuttgart · New York

Copper-Catalyzed Tandem Synthesis of Tetrasubstituted Pyrimidines from Alkynes, Sulfonyl Azides, Trichloroacetonitrile, and Tetramethylguanidine

Issa Yavari*
Department of Chemistry, Tarbiat Modares University, PO Box 14115-175, Tehran, Iran   Fax: +98(21)82883455   Email: yavarisa@modares.ac.ir
,
Manijeh Nematpour
Department of Chemistry, Tarbiat Modares University, PO Box 14115-175, Tehran, Iran   Fax: +98(21)82883455   Email: yavarisa@modares.ac.ir
› Author Affiliations
Further Information

Publication History

Received: 27 October 2012

Accepted after revision: 05 December 2012

Publication Date:
04 January 2013 (online)

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Abstract

The synthesis of a novel class of pyrimidine derivatives via a copper-catalyzed tandem reaction of trichloroacetonitrile, 1,1,3,3-tetramethylguanidine, sulfonyl azides, and terminal alkynes is described.

Keywords

pyrimidine - ketenimines - tandem reaction - sulfonyl azide - terminal alkyne - trichloroacetonitrile - 1,1,3,3-tetramethylguanidine
 

  • References and Notes

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  • 19 Typical Procedure for the Preparation of Compounds 5 Compounds 3 (1 mmol) and 4 (1 mmol) were dissolved in MeCN (2 mL) and stirred for 30 min. Then, a mixture of sulfonyl azide 2 (1.2 mmol), alkyne 1 (1 mmol), CuI (0.1 mmol), and Et3N (1 mmol) in MeCN (3 mL) was slowly added to the mixture and stirred at r.t. under N2 atmosphere. After completion of the reaction [about 8 h; TLC (EtOAc–hexane = 1:5) monitoring], the mixture was diluted with CH2Cl2 (2 mL) and aq NH4Cl solution (3 mL), stirred for 30 min, and the layers were separated. The aqueous layer was extracted with CH2Cl2 (3 × 3 mL). The combined organic fractions were dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by flash column chromatography [silica gel (230–400 mesh; Merck), hexane–EtOAc = 5:1] to give the product. N-[6-(Dimethylamino)-5-phenyl-2-(trichloromethyl)-pyrimidin-4-yl]-4-methylbenzenesulfonamide (5a) Cream powder; mp 159–161 °C; yield 0.40 g (83%). IR (KBr): νmax = 3061, 1682, 1590, 1445, 1375, 1172, 1071, 754 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.87 (3 H, s, Me), 2.95 (6 H, s, NMe2), 7.07 (2 H, d, 3 J = 7.4 Hz, Ar), 7.18 (1 H, t, 3 J = 7.4 Hz, Ar), 7.28 (2 H, t, 3 J = 7.4 Hz, Ar), 7.39 (2 H, d, 3 J = 7.9 Hz, Ar), 7.91 (2 H, d, 3 J = 7.9 Hz, Ar), 8.03 (1 H, s, NH). 13C NMR (125.7 MHz, CDCl3): δ = 32.4 (Me), 37.5 (NMe2), 90.4 (CCl3), 110.0 (C), 122.5 (C), 127.4 (2 CH), 128.7 (2 CH), 129.2 (CH), 130.7 (2 CH), 132.5 (2 CH), 142.1 (C), 147.3 (C), 163.6 (C), 168.9 (C), 171.0 (C). MS: m/z (%) = 484 (1) [M+], 439 (6), 406 (12), 392 (16), 367 (21), 170 (23), 155 (100), 116 (43), 91 (70), 77 (51), 44 (31). Anal. Calcd (%) for C20H19Cl3N4O2S (484.03): C, 49.45; H, 3.94; N, 11.53. Found: C, 49.68; H, 4.02; N, 11.62. N-[6-(Dimethylamino)-5-phenyl-2-(trichloromethyl)-pyrimidin-4-yl]benzenesulfonamide (5b) Cream powder; mp 167–170 °C; yield 0.40 g (87%). IR (KBr): νmax = 3060, 1681, 1595, 1441, 1373, 1270, 1182, 1072, 750 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.96 (6 H, s, NMe2), 7.25–7.31 (3 H, m, Ph), 7.45 (2 H, d, 3 J = 7.4 Hz, Ar), 7.58 (2 H, t, 3 J = 7.4 Hz, Ar), 7.69 (1 H, t, 3 J = 7.9 Hz, Ar), 8.00 (2 H, d, 3 J = 7.9 Hz, Ar), 8.07 (1 H, s, NH). 13C NMR (125.7 MHz, CDCl3): δ = 37.5 (NMe2), 90.4 (CCl3), 110.3 (C), 122.5 (C), 127.4 (2 CH), 128.7 (2 CH), 129.2 (CH), 130.2 (2 CH), 132.5 (2 CH), 135.7 (CH), 144.8 (C), 163.6 (C), 167.8 (C), 171.1 (C). MS: m/z (%) = 470 (1) [M+], 425 (3), 392 (21), 314 (17), 156 (31), 141 (100), 91 (71), 77 (50), 44 (31). Anal. Calcd (%) for C19H17Cl3N4O2S (470.01): C, 48.37; H, 3.63; N, 11.88. Found: C, 48.63; H, 3.69; N, 12.01. N-[6-(Dimethylamino)-5-phenyl-2-(trichloromethyl)-pyrimidin-4-yl]methanesulfonamide (5c) Cream powder; mp 123–125 °C; yield 0.32 g (79%). IR (KBr): νmax = 3031, 1684, 1592, 1446, 1361, 1278, 1170, 1073, 757 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.93 (6 H, s, NMe2), 3.65 (3 H, s, Me), 7.25–7.35 (3 H, m, Ph), 7.48 (2 H, d, 3 J = 7.4 Hz, Ar), 8.11 (1 H, s, NH). 13C NMR (125.7 MHz, CDCl3): δ = 33.0 (Me), 37.8 (NMe2), 90.4 (CCl3), 110.1 (C), 122.6 (C), 128.7 (2 CH), 129.2 (CH), 132.5 (2 CH), 163.0 (C), 167.0 (C), 170.0 (C). MS: m/z (%) = 409 (1) [M+], 363 (11), 330 (14), 329 (18), 314 (17), 116 (31), 94 (100), 78 (54), 77 (32), 44 (22). Anal. Calcd (%) for C14H15Cl3N4O2S (409.72): C, 41.04; H, 3.69; N, 13.67. Found: C, 41.42; H, 3.76; N, 13.52. N-[6-(Dimethylamino)-5-propyl-2-(trichloromethyl)-pyrimidin-4-yl]-4-methylbenzenesulfonamide (5d) Cream powder; mp 113–115 °C; yield 0.29 g (65%). IR (KBr): νmax = 3039, 1633, 1590, 1368, 1218, 1018, 751 cm–1. 1H NMR (500 MHz, CDCl3): δ = 0.96 (3 H, t, 3 J = 6.8 Hz, Me), 1.48–1.55 (2 H, m, CH2), 2.13 (2 H, t, 3 J = 6.8 Hz, CH2), 2.45 (3 H, s, Me), 3.07 (6 H, s, NMe2), 7.38 (2 H, d, 3 J = 7.9 Hz, Ar), 7.89 (2 H, d, 3 J = 7.9 Hz, Ar), 8.21 (1 H, s, NH). 13C NMR (125.7 MHz, CDCl3): δ = 13.7 (Me), 20.8 (CH2), 22.3 (CH2), 33.3 (Me), 38.6 (NMe2), 90.4 (CCl3), 111.0 (C), 127.4 (2 CH), 129.6 (2 CH), 142.1 (C), 147.3 (C), 164.7 (C), 168.6 (C), 170.0 (C). MS: m/z (%) = 450 (1) [M+], 406 (11), 391 (8), 343 (14), 280 (17), 170 (21), 155 (100), 116 (31), 91 (45), 44 (20), 43 (30). Anal. Calcd (%) for C17H21Cl3N4O2S (450.05): C, 45.19; H, 4.68; N, 12.40. Found: C, 45.54; H, 4.55; N, 12.51. N-[6-(Dimethylamino)-5-propyl-2-(trichloromethyl)-pyrimidin-4-yl]benzenesulfonamide (5e) Cream powder; mp 100–103 °C; yield 0.27 g (63%). IR (KBr): νmax = 3061, 1680, 1571, 1435, 1377, 1235, 1163, 1075, 748 cm–1. 1H NMR (500 MHz, CDCl3): δ = 0.97 (3 H, t, 3 J = 6.8 Hz, Me), 1.48–1.56 (2 H, m, CH2), 2.12 (2 H, t, 3 J = 6.8 Hz, CH2), 3.10 (6 H, s, NMe2), 7.60 (2 H, t, 3 J = 7.8 Hz, Ar), 7.74 (1 H, t, 3 J = 7.8 Hz, Ar), 8.00 (2 H, d, 3 J = 7.8 Hz, Ar), 8.24 (1 H, s, NH). 13C NMR (125.7 MHz, CDCl3): δ = 13.7 (Me), 20.8 (CH2), 22.4 (CH2), 38.7 (NMe2), 91.0 (CCl3), 110.6 (C), 127.3 (2 CH), 130.1 (2 CH), 135.7 (CH), 144.8 (C), 164.8 (C), 168.9 (C), 171.0 (C). MS: m/z (%) = 436 (1) [M+], 392 (15), 319 (13), 296 (21), 280 (17), 156 (45), 144 (100), 116 (35), 77 (49), 44 (25), 43 (22). Anal. Calcd (%) for C16H19Cl3N4O2S (436.03): C, 43.90; H, 4.37; N, 12.80. Found: C, 44.21; H, 4.48; N, 12.91. N-[6-(Dimethylamino)-5-propyl-2-(trichloromethyl)-pyrimidin-4-yl]methanesulfonamide (5f) Cream powder; mp 90–93 °C; yield 0.22 g (60%). IR (KBr): νmax = 3064, 1679, 1565, 1459, 1370, 1271, 1180, 1049, 749 cm–1. 1H NMR (500 MHz, CDCl3): δ = 0.99 (3 H, t, 3 J = 6.8 Hz, Me), 1.49–1.57 (2 H, m, CH2), 2.14 (2 H, t, 3 J = 6.8 Hz, CH2), 2.96 (6 H, s, NMe2), 3.56 (3 H, s, Me), 8.28 (1 H, s, NH). 13C NMR (125.7 MHz, CDCl3): δ = 13.7 (Me), 20.8 (CH2), 22.3 (CH2), 33.0 (Me), 39.7 (NMe2), 90.4 (CCl3), 111.0 (C), 165.6 (C), 167.7 (C), 170.0 (C). MS: m/z (%) = 374 (1) [M+], 330 (11), 329 (9), 295 (25), 280 (13), 116 (30), 94 (100), 78 (39), 44 (29), 43 (26). Anal. Calcd (%) for C11H17Cl3N4O2S (374.01): C, 35.17; H, 4.56; N, 14.91. Found: C, 35.40; H, 4.63; N, 15.03. N-[5-Butyl-6-(dimethylamino)-2-(trichloromethyl)-pyrimidin-4-yl]-4-methylbenzenesulfonamide (5g) Cream powder; mp 119–122 °C; yield 0.28 g (60%). IR (KBr): νmax = 3032, 1627, 1551, 1450, 1365, 1222, 1177, 1079, 739 cm–1. 1H NMR (500 MHz, CDCl3): δ = 0.92 (3 H, t, 3 J = 6.8 Hz, Me), 1.36–1.43 (2 H, m, CH2), 1.46–1.51 (2 H, m, CH2), 2.14 (2 H, t, 3 J = 6.8 Hz, CH2), 2.50 (3 H, s, Me), 3.00 (6 H, s, NMe2), 7.39 (2 H, d, 3 J = 8.0 Hz, Ar), 7.92 (2 H, d, 3 J = 8.0 Hz, Ar), 8.30 (1 H, s, NH). 13C NMR (125.7 MHz, CDCl3): δ = 13.9 (Me), 18.5 (CH2), 21.8 (CH2), 22.2 (CH2), 33.8 (Me), 39.3 (NMe2), 90.4 (CCl3), 110.1 (C), 127.5 (2 CH), 129.6 (2 CH), 142.0 (C), 147.3 (C), 163.7 (C), 169.0 (C), 172.0 (C). MS: m/z (%) = 464 (1) [M+], 420 (8), 406 (11), 347 (13), 170 (21), 155 (100), 116 (50), 91 (42), 57 (44), 44 (45). Anal. Calcd (%) for C18H23Cl3N4O2S (464.06): C, 46.41; H, 4.98; N, 12.03. Found: C, 46.67; H, 5.07; N, 12.16. N-[5-Butyl-6-(dimethylamino)-2-(trichloromethyl)-pyrimidin-4-yl]benzenesulfonamide (5h) Cream powder; mp 111–114 °C; yield 0.26 g (57%). IR (KBr): νmax = 3031, 1613, 1592, 1451, 1376, 1220, 1177, 1079, 743 cm–1. 1H NMR (500 MHz, CDCl3): δ = 0.88 (3 H, t, 3 J = 6.8 Hz, Me), 1.35–1.41 (2 H, m, CH2), 1.43–1.50 (2 H, m, CH2), 2.13 (2 H, t, 3 J = 6.8 Hz, CH2), 2.96 (6 H, s, NMe2), 7.61 (2 H, t, 3 J = 7.8 Hz, Ar), 7.71 (1 H, t, 3 J = 7.8 Hz, Ar), 7.99 (2 H, d, 3 J = 7.8 Hz, Ar), 8.18 (1 H, s, NH). 13C NMR (125.7 MHz, CDCl3): δ = 13.9 (Me), 18.4 (CH2), 20.8 (CH2), 22.2 (CH2), 38.3 (NMe2), 90.1 (CCl3), 111.4 (C), 127.3 (2 CH), 130.2 (2 CH), 135.7 (CH), 144.8 (C), 164.3 (C), 169.0 (C), 171.0 (C). MS: m/z (%) = 450 (1) [M+], 406 (6), 392 (10), 373 (22), 294 (25), 156 (100), 141 (23), 116 (50), 57 (41), 44 (22). Anal. Calcd (%) for C17H21Cl3N4O2S (450.05): C, 45.19; H, 4.68; N, 12.40. Found: C, 45.52; H, 4.71; N, 12.52. N-[5-Butyl-6-(dimethylamino)-2-(trichloromethyl)-pyrimidin-4-yl]methanesulfonamide (5i) Cream powder; mp 95–98 °C; yield 0.20 g (52%). IR (KBr): νmax = 3030, 1669, 1582, 1451, 1376, 1179, 1078, 741 cm–1. 1H NMR (500 MHz, CDCl3): δ = 0.89 (3 H, t, 3 J = 6.8 Hz, Me), 1.34–1.40 (2 H, m, CH2), 1.44–1.52 (2 H, m, CH2), 2.14 (2 H, t, 3 J = 6.8 Hz, CH2), 2.96 (6 H, s, NMe2), 3.46 (3 H, s, Me), 8.24 (1 H, s, NH). 13C NMR (125.7 MHz, CDCl3): δ = 13.9 (Me), 18.4 (CH2), 20.8 (CH2), 22.7 (CH2), 33.6 (Me), 38.3 (NMe2), 90.1 (CCl3), 111.0 (C), 165.8 (C), 167.9 (C), 171.3 (C). MS: m/z (%) = 388 (1) [M+], 343 (8), 315 (10), 294 (22), 279 (25), 116 (23), 94 (100), 78 (23), 44 (43). Anal. Calcd (%) for C12H19Cl3N4O2S (388.03): C, 36.98; H, 4.91; N, 14.38. Found: C, 37.29; H, 4.85; N, 14.47.
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