Synlett, Table of Contents Synlett 2016; 27(04): 595-598DOI: 10.1055/s-0035-1560905 letter © Georg Thieme Verlag Stuttgart · New YorkHighly Regioselective Synthesis of Pyrazole Derivatives Using a 1,3-Dipolar Cycloaddition Approach Authors Author Affiliations Abdolali Alizadeh* a Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran Email: aalizadeh@modares.ac.ir Email: abdol_alizad@yahoo.com Leila Moafi a Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran Email: aalizadeh@modares.ac.ir Email: abdol_alizad@yahoo.com Long-Guan Zhu b Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. of China Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) Abstract We report a simple and regioselective procedure for the synthesis of 1H-pyrazol-5-yl (2-hydroxyphenyl)methanone derivatives. This process includes the 1,3-dipolar cycloaddition reaction of nitrile imines generated in situ from hydrazonoyl chloride and triethylamine with 3-formylchromones. Key words Key words3-formylchromone - pyrazole - hydrazonoyl chloride - nitrile imine - 1,3-dipolar cycloaddition Full Text References References and Notes 1 Sabitha G. Aldrichimica Acta 1996; 29: 15 2 Ghosh CK. Heterocycles 2004; 63: 2875 3a Lahm GP, Cordova D, Barry JD. Bioorg. Med. Chem. 2009; 17: 4127 3b Shiga Y, Okada L, Ineda Y, Takizawa E, Fukuchi T. J. Pestic. Sci. (Tokyo, Japan) 2003; 28: 313 4a Bekhit AA, Abdel-Aziem T. Bioorg. Med. Chem. 2004; 12: 1935 4b de Paulis T, Hemstapat K, Chen Y, Zhang Y, Saleh S, Alagille D, Baldwin RM, Tamagnan GD, Conn PJ. J. Med. Chem. 2006; 49: 3332 5a Yang L, Okuda F, Kobayashi K, Nozaki K, Tanabe Y, Ishii Y, Haga M. Inorg. Chem. 2008; 47: 7154 5b Chang EM, Lee CT, Chen CY, Wong FF, Yeh MY. Aust. J. Chem. 2008; 61: 342 6 Hashem AI, Youssef AS. A, Kandeel KA, Abou-Elmagd WS. I. Eur. J. Med. Chem. 2007; 42: 934 7 Balbi A, Anzaldi M, Maccio C, Aiello C, Mazzei M, Gangemi R, Castagnola P, Miele M, Rosano C. Eur. J. Med. Chem. 2011; 46: 5293 8 Damljanovic I, Vukicevic M, Radulovic N, Palic R, Ellmerer E, Ratkovic Z, Joksovic MD, Vukicevic RD. Bioorg. Chem. Lett. 2009; 19: 1093 9 Bekhit AA, Ashour HM.A, Ghany YS. A, Bekhit AE. A, Baraka AM. Eur. J. Med. Chem. 2008; 43: 456 10a Kowalcyk R, Skarzewski J. Tetrahedron 2005; 61: 623 10b Ojwach SO, Darkwa J. Inorg. Chim. Acta 2011; 363: 1947 11 Gladstone WA, Aylward JB, Norman RO. C. J. Chem. Soc. 1969; 2587 12 Huisgen R, Seidel M, Wallibillich G, Knupfer H. Tetrahedron 1962; 17: 3 13 Sun A, Ye JH, Yu H, Zhang W, Wang X. Tetrahedron Lett. 2014; 55: 889 14 Khan KM, Ambreen N, Mughal UR, Jalil S, Choudhary MI, Perveen S. Eur. J. Med. Chem. 2010; 45: 4058 15 Gadakh AV, Rindhe SS, Pandit C, Karale BK. Bioorg. Med. Chem. Lett. 2010; 20: 5572 16 Coutinho DL. M, Fernandes PS. Indian J. Chem. 1992; 31: 573 17 Ghosh CK, Mukhopadhyay KK. J. Indian Chem. Soc. 1978; 55: 386 18 Ito K, Maruyama J. J. Heterocycl. Chem. 1988; 25: 1681 19 Ghosh CK, Bandyopadhyay C, Morin C. J. Chem. Soc., Perkin Trans. 1 1983; 1989 20 M'Sadek M, Rammah M, Schmit G, Vebrel J. Bull. Soc. Chim. Belg. 1992; 101: 323 21 Alizadeh A, Moafi L, Ghanbaripour R, Hossein Abadi M, Zhu Z, Kubicki M. Tetrahedron 2015; 71: 3954 22 General Procedure A mixture of hydrazonoyl chloride derivative 1 (1 mmol) and Et3N (1 mmol) in EtOH (3 mL) was stirred at r.t. for 10 min. Then 3-formylchromone 2 (1 mmol) was added to the above mixture, and the reaction was stirred at r.t. for 4 h. After completion of the reaction, the precipitate washed with EtOH to afford the pure product 3 in high yield. Representative Analytical Data (1,3-Diphenyl-1H-pyrazol-5-yl)(2-hydroxyphenyl)methanone (3a) White powder; yield 0.29 g (88%); mp 106–107 °C. IR (KBr): 3430 (OH), 1617 (CO), 1527 and 1487 (Ar), 1210 (CO) cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 6.97 (1 H, t, 3 J HH = 6.8 Hz, CH of Ar), 6.98 (1 H, d, 3 J HH = 6.8 Hz, CH of Ar), 7.37 (1 H, s, CH of pyrazole), 7.39–7.53 (9 H, m, 9 × CH of Ar), 7.70 (1 H, d, 3 J HH = 8.0 Hz, CH of Ar), 7.95 (2 H, d, 3 J HH = 7.2 Hz, 2 × CH ortho of Ph), 10.71 (1 H, s, OH). 13C NMR (100 MHz, DMSO-d 6): δ = 109.8 (CH of pyrazole), 117.1 (CH of Ar), 119.3. (CH of Ar), 122.9 (C ipso CO), 124.5 (2 × CH ortho of Ph), 125.5 (2 × CH ortho of Ph), 127.9 (CH para of Ph), 128.4 (CH para of Ph), 128.8 (2 × CH meta of Ph), 128.9 (2 × CH meta of Ph), 131.4 (CH of Ar), 131.7 (C ipso C3), 135.4 (CH of Ar), 139.6 (C5 of pyrazole), 141.5 (C ipso N), 150.7 (C3 of pyrazole), 158.7 (COH), 187.5 (CO). MS (EI, 70 eV): m/z = 340 [M+], 295, 220, 121, 77, 65. Anal. Calcd (%) for C22H16N2O2 (340.38): C, 77.63; H, 4.74; N, 8.23. Found: C, 77.70; H, 4.70; N, 8.31. Crystal Data for 3a C22H16N2O2 (CCDC 1058597): MW = 340.37, orthorhombic, P-1, a = 12.3063(6) Å, b = 13.4269(6) Å, c = 21.6550(13) Å, α = 90.00, β = 90.00, γ = 90.00, V = 3578.2(3) Å3, Z = 8, D c = 1.264 mg m–3, F(000) = 1424, crystal dimension 0.43 × 0.4×0.38 mm, radiation, Mo Kα (λ = 0.71073 Å), 2.93 ≤ 2θ ≤ 25.09, intensity data were collected at 293(2) K with a Bruker APEX area-detector diffractometer, and employing ω/2θ scanning technique, in the range of –14 ≤ h ≤ 14, –15 ≤ k ≤ 16, –25 ≤ l ≤ 20; the structure was solved by a direct method, all nonhydrogen atoms were positioned and anisotropic thermal parameters refined from 2331 observed reflections with R(into) = 0.0659 by a full-matrix least-squares technique converged to R = 0.0452 and R aw = 0.1728 [I > 2σ(I)]. (5-Chloro-2-hydroxyphenyl)(1,3-diphenyl-1H-pyrazol-5-yl)-methanone (3b) Yellow powder; yield 0.32 g (85%); mp 122 °C. IR (KBr): 3422 (OH), 1619 (CO), 1533 and 1492 (Ar), 1199 (CO) cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 6.94 (1 H, d, 3 J HH = 8.8 Hz, CH of Ar), 7.40 (1 H, s, CH of pyrazole), 7.42–7.52 (9 H, m, 9 × CH of Ar), 7.56 (1 H, d, 3 J HH = 2.8 Hz, CH of Ar), 7.94 (2H, d, 3 J HH = 7.2 Hz, 2 × CH ortho of Ph), 10.62 (1 H, s, OH). 13C NMR (100 MHz, DMSO-d 6): δ = 110.2 (CH of pyrazole), 118.7 (CH of Ar), 122.7 (C ipso CO), 124.8 (2 × CH ortho of Ph), 125.5 (2 × CH ortho of ph), 125.9 (C ipso Cl), 128.1 (CH para of Ph), 128.4 (CH para of Ph), 128.8 (4 × CH meta of 2 × Ph), 129.5 (CH of Ar), 131.7 (C ipso C3), 133.6 (CH of Ar), 139.6 (C5 of pyrazole), 141.7 (C ipso N), 150.7 (C3 of pyrazole), 155.9 (COH), 184.8 (CO). MS (EI, 70 eV): m/z = 376 [M+ + 2], 374 [M+], 329, 220, 116, 89, 77. Anal. Calcd (%) for C22H15ClN2O2 (374.82): C, 70.50; H, 4.03; N, 7.47. Found: C, 70.56; H, 4.08; N, 7.40. [3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-5-yl](2-hydroxyphenyl)methanone (3c) Yellow powder; yield 0.31 g (85%); mp 175 °C. IR (KBr): 3390 (OH), 1615 (CO), 1521 and 1489 (Ar), 1211 (CO) cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 6.95–6.97 (2 H, m, 2 × CH of Ar), 7.42–7.50 (9 H, m, 9 × CH of Ph), 7.68 (1 H, d, 3 J HH = 7.9 Hz, CH of Ar), 7.98 (2 H, d, 3 J HH = 6.4 Hz, 2 × CH of Ar), 10.64 (1 H, s, OH). 13C NMR (100 MHz, DMSO-d 6): δ = 109.9 (CH of pyrazole), 117.1 (CH of Ar), 119.3 (CH of Ar), 123.1 (C ipso CO), 124.5 (2 × CH ortho of Ph), 127.3 (2 × CH of Ar), 128.1 (CH para of Ph), 128.8 (2 × CH of Ar), 128.9 (2 × CH meta of Ph), 130.7 (C ipso Cl), 131.4 (CH of Ar), 132.9 (C ipso C3), 135.4 (CH of Ar), 139.6 (C5 of pyrazole), 141.9 (C ipso N), 149.6 (C3 of pyrazole), 156.1 (COH), 184.7 (CO). MS (EI, 70 eV): m/z = 376 [M+ + 2], 374 [M+], 329, 254, 121, 77, 65. Anal. Calcd (%) for C22H15ClN2O2 (374.82): C, 70.50; H, 4.03; N, 7.47. Found: C, 70.42; H, 3.95; N, 7.40. (5-Chloro-2-hydroxyphenyl)(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-5-yl)methanone (3d) Yellow powder; yield 0.36 g (88%); mp 152–154 °C. IR (KBr): 3433 (OH), 1622 (CO), 1535 and 1487 (Ar), 1200 (CO) cm–1. 1H NMR (300.13 MHz, DMSO-d 6): δ = 6.89 (1 H, d, 3 J HH = 8.8 Hz, CH of Ar), 7.39–7.50 (9 H, m, 9 × CH), 7.53 (1 H, d, 4 J HH = 2.5 Hz, CH of Ar), 7.95 (2 H, d, 3 J HH = 8.5 Hz, 2 × CH ortho of Ar), 10.56 (1 H, s, OH). 13C NMR (75 MHz, DMSO-d 6): δ = 110.3 (CH of pyrazole), 118.8 (CH of Ar), 122.6 (C ipso CO), 124.8 (2 × CH ortho of Ph), 126.0 (C ipso Cl), 127.3 (2 × CH of Ar), 128.2 (CH para of Ph), 128.82 (2 × CH of Ar), 128.86 (2 × CH meta of Ph), 129.5 (C ipso C3), 130.6 (CH of Ar), 132.9 (CH of Ar), 133.6 (C ipso Cl), 139.6 (C5 of pyrazole), 141.9 (C ipso N), 149.6 (C3 of pyrazole), 156.1 (COH), 184.7 (CO). MS (EI, 70 eV): m/z = 412 [M+ + 4], 410 [M+ + 2], 408 [M+], 365, 254, 155, 99, 77. Anal. Calcd (%) for C22H14Cl2N2O2 (409.27): C, 64.56; H, 3.45; N, 6.84. Found: C, 64.51; H, 3.51; N, 6.78.
