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

Issa Yavari; Manijeh Nematpour

doi:10.1055/s-0032-1317951

Synlett, Inhaltsverzeichnis

Synlett 2013; 24(2): 165-168
DOI: 10.1055/s-0032-1317951

letter

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

Authors

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

Abstract

Alle Artikel dieser Rubrik

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

Volltext

Referenzen

References and Notes
1 Sasada T, Kobayashi F, Sakai N, Konakahara T. Org. Lett. 2009; 11: 2161
2 Ahmad OK, Hill MD, Movassaghi M. J. Org. Chem. 2009; 74: 8460
3 Barthakur MG, Borthakur M, Devi P, Saikia CJ, Saikia A, Bora U, Chetia A, Boruah RC. Synlett 2007; 223
4 Heys L, Moore CG, Murphy PJ. Chem. Soc. Rev. 2000; 29: 57
5 Rewcastle GW. Comprehensive Heterocyclic Chemistry III: Pyrimidines and their Benzo Derivatives. Vol. 8. Elsevier; Oxford: 2008: 117-272
6 von Angerer S. Six-Membered Hetarenes with Two Identical Heteroatoms: Pyrimidines. In Science of Synthesis. Vol. 16. Thieme; Stuttgart: 2003: 379-572
7 Brown DJ, Evans RF, Cowden WB, Fenn MD. The Pyrimidines . In Chemistry of Heterocyclic Compounds . Vol. 52. Taylor EC. Wiley; New York: 1994: 1
8 Bae I, Han H, Chang S. J. Am. Chem. Soc. 2005; 127: 2038
9 Staudinger H, Hauser E. Helv. Chim. Acta 1921; 4: 887
10 Lu P, Wang YG. Synlett 2010; 166
11 Hein JE, Fokin VV. Chem. Soc. Rev. 2010; 39: 1302
12 Yoo EJ, Chang S. Curr. Org. Chem. 2009; 13: 1766
13 Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. Angew. Chem. Int. Ed. 2002; 41: 2596
14 Tornøe CW, Christensen C, Meldal M. J. Org. Chem. 2002; 67: 3057
15 Jin H, Zhou B, Wu Z, Shen Y, Wang Y. Tetrahedron 2011; 67: 1178
16 Yavari I, Nematpour M. Synlett 2012; 23: 2215
17 Yavari I, Nematpour M, Yavari S, Sadeghizadeh F. Tetrahedron Lett. 2012; 53: 1889
18 Yavari I, Nematpour M. Mol. Diversity 2012; 16: 651
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): ν_max = 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): ν_max = 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): ν_max = 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): ν_max = 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): ν_max = 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): ν_max = 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): ν_max = 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): ν_max = 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): ν_max = 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.
20 Yoo EJ, Ahlquist M, Kim SH, Bae I, Fokin VV, Sharpless KB, Chang S. Angew. Chem. Int. Ed. 2007; 46: 1730
21 Cassidy MP, Raushel J, Fokin VV. Angew. Chem. Int. Ed. 2006; 45: 3154
22 Yoo EJ, Ahlquist M, Bae I, Sharpless KB, Fokin VV, Chang S. J. Org. Chem. 2008; 73: 5520