The Use of Calcium Carbide in the Synthesis of 1-Monosubstituted Aryl 1,2,3-Triazole via Click Chemistry

Abstract

The synthesis of 1-monosubstituted aryl 1,2,3-triazoles was achieved using calcium carbide as a source of acetylene. The copper-catalyzed 1,3-dipolar cycloaddition reactions were carried out without nitrogen protection and in a MeCN-H₂O mixture. The yields ranged from moderate to excellent. The reaction conditions were found to be successful for aryl azide reactants, including analogues with various functionalities.

calcium carbide - 1-monosubstitued 1,2,3-triazole - copper-catalyzed - click chemistry

References and Notes

<A NAME="RW13409ST-1A">1a</A> Kolb HC. Finn MG. Sharpless KB. Angew. Chem. Int. Ed.  2001,  40:  2004 

<A NAME="RW13409ST-1B">1b</A> Bock VD. Hiemstra H. Maarseveen JH. J. Org. Chem.  2006,  5:  919 

<A NAME="RW13409ST-1C">1c</A> Fournier D. Hoogenboom R. Schubert US. Chem. Soc. Rev.  2007,  36:  1369 

<A NAME="RW13409ST-1D">1d</A> Nandivada H. Jiang X. Lahann J. Adv. Mater.  2007,  19:  2197 

<A NAME="RW13409ST-1E">1e</A> Lutz JF. Angew. Chem. Int. Ed.  2007,  46:  1018 

<A NAME="RW13409ST-1F">1f</A> Tron GC. Pirali T. Billington RA. Canonico PL. Sorba G. Genazzani AA. Med. Res. Rev.  2008,  28:  278 

<A NAME="RW13409ST-1G">1g</A> Hanelt S. Liebscher J. Synlett  2008,  1058 

<A NAME="RW13409ST-2A">2a</A> Rostovtsev VV. Green LG. Fokin VV. Sharpless KB. Angew. Chem. Int. Ed.  2002,  41:  2596 

<A NAME="RW13409ST-2B">2b</A> Tornoe CW. Christensen C. Meldal M. J. Org. Chem.  2002,  67:  3057 

<A NAME="RW13409ST-2C">2c</A> Zhang L. Chen X. Xue P. Sun HHY. Williams ID. Sharpless KB. Fokin VV. Jia G. J. Am. Chem. Soc.  2005,  127:  15998 

<A NAME="RW13409ST-2D">2d</A> Rasmussen LK. Boren BC. Fokin VV. Org. Lett.  2007,  9:  5337 

<A NAME="RW13409ST-2E">2e</A> Boren BC. Narayan S. Rasmussen LK. Shang L. Zhao H. Lin Z. Jia G. Fokin VV. J. Am. Chem. Soc.  2008,  130:  8923 

<A NAME="RW13409ST-2F">2f</A> Wu LY. Xie YX. Chen ZS. Liu YN. Liang YM. Synlett  2009,  1453 

<A NAME="RW13409ST-2G">2g</A> Yan ZY. Wei HL. Wu LY. Zhao YB. Liang YM. Tetrahedron: Asymmetry  2006,  17:  3288 

<A NAME="RW13409ST-2H">2h</A> Yan ZY. Zhao YB. Fan MJ. Liu WM. Liang YM. Tetrahedron  2005,  61:  9331 

<A NAME="RW13409ST-2I">2i</A> Cristau HJ. Cellier PP. Spindler JF. Taillefer M. Chem. Eur. J.  2004,  10:  5607 

<A NAME="RW13409ST-3">3</A> De O. Ronaldo N. Sinou D. Srivastava RM.
J. Carbohydr. Chem.  2006,  25:  407 

<A NAME="RW13409ST-4A">4a</A> Andersen J. Bolvig S. Liang X. Synlett  2005,  2941 

<A NAME="RW13409ST-4B">4b</A> Chan DCM. Laughton CA. Queener SF. Stevens MFG. Bioorg. Med. Chem.  2002,  10:  3001 

<A NAME="RW13409ST-4C">4c</A> Fletcher JT. Walz SE. Keeney ME. Tetrahedron Lett.  2008,  49:  7030 

<A NAME="RW13409ST-5A">5a</A> Biagi G. Livi O. Scartoni V. Verugi E. Farmaco  1988,  43:  597 

<A NAME="RW13409ST-5B">5b</A> Haebich D. Barth W. Roesner M. Heterocycles  1989,  29:  2083 

<A NAME="RW13409ST-5C">5c</A> Kadaba PK. J. Org. Chem.  1992,  57:  3075 

<A NAME="RW13409ST-5D">5d</A> Sasaki T. Eguchi S. Yamaguchi M. Esaki T. J. Org. Chem.  1981,  46:  1800 

<A NAME="RW13409ST-6">6</A> Naud J. Lemke C. Goudreau N. Beaulieu E. White PD. Bioorg. Med. Chem. Lett.  2008,  18:  3400 

<A NAME="RW13409ST-7">7</A> Broggini G. De M I. Martinelli M. Paladino G. Polati T. Terraneo A. Synthesis  2005,  2246 

<A NAME="RW13409ST-8">8</A>

General Procedure for the Synthesis of 2 (Conditions A)
To a flask were added MeCN-H₂O mixture (12 mL
v/v = 2:1), azide (0.5 mmol), CuI (19 mg, 0.1 mmol), Na ascorbate (20 mg, 0.1 mmol), CaC₂ (42 mg, 0.65 mmol). The mixture was stirred at r.t., and the reaction was monitored by TLC. After reaction completed, the system was neutralized to pH = 5 with aq HCl (6%), and the mixture was then extracted with EtOAc (3 × 30 mL). The organic layer was separated, washed with H₂O and sat. brine, and dried over anhyd NaSO₄. Evaporation of the solvent gave the crude product, which was subjected to column chromatography (silica gel, EtOAc-PE) to afford 1-substitued 1,2,3-triazoles 2.

<A NAME="RW13409ST-9">9</A>

General Procedure for the Synthesis of 2 (Conditions B)
To a sealed tube were added MeCN-H₂O mixture (12 mL
v/v = 2:1), azide (0.5 mmol), CuI (19 mg, 0.1 mmol), Na ascorbate (20 mg, 0.1 mmol), CaC₂ (42 mg, 0.65 mmol). The mixture was stirred at 90 ˚C, and the reaction was monitored by TLC. After reaction completed, the system was neutralized to pH = 5 with aq HCl (6%), and the mixture was then extracted with EtOAc (3 × 30 mL). The organic layer was separated, washed with H₂O and sat. brine, and dried over anhyd NaSO₄. Evaporation of the solvent gave the crude product, which was subjected to column chromatography (silica gel, EtOAc-PE) to afford
1-substitued 1,2,3-triazoles 2.

<A NAME="RW13409ST-10">10</A>

All compounds gave satisfactory analytical and spectral data.
Selected Data
(E)-1-[4-(2-Bromovinyl)phenyl]-1H-1,2,3-triazole (2j): yellow solid, mp 147.8-148.1 ˚C. IR (KBr): 1599, 1511, 1435, 977, 783 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 8.00 (1 H, s), 7.85 (1 H, s), 7.73 (2 H, d, J = 9.0 Hz), 7.46 (2 H, d, J = 9.0 Hz), 7.16 (1 H, d, J = 13.8 Hz), 6.88 (1 H, d, J = 13.8 Hz). ^¹³C NMR (125 MHz, CDCl₃): δ = 136.5, 136.4, 135.7, 134.5, 127.3, 121.5, 120.8, 108.3. ESI-MS: m/z (%) = 251(99) [M + 2]⁺, 249(100) [M⁺]. HRMS: m/z calcd for C₁₀H₈ ⁷⁹BrN₃: 248.9902; found: 248.9906
(E)-1-[2-(2-Bromovinyl)phenyl]-1H-1,2,3-triazole (2k): yellow solid, mp 100.9-101.5 ˚C. IR (KBr): 1609, 1496, 1507, 1447, 1193, 983, 783 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.89 (1 H, s), 7.80 (1 H, s), 7.59-7.57 (1 H, m), 7.52-7.46 (2H, m), 7.42 (1 H, d, J = 8.0 Hz), 6.84 (1 H, d, J = 14.0 Hz), 6.78 (1 H, d, J = 14.0 Hz). ^¹³C NMR (125 MHz, CDCl₃): δ = 134.3, 134.0, 131.7, 131.6, 130.1, 129.1, 127.1, 126.5, 125.7, 110.6. ESI-MS: m/z (%) = 251(99)
[M + 2]⁺, 249(100) [M⁺]. HRMS: m/z calcd for C₁₀H₈ ⁷⁹BrN₃: 248.9902; found: 248.9908.