Copper(II)-Promoted Regioselective Synthesis of 1,4-Disubstituted 1,2,3-Triazoles in Water

Abstract

A high-yielding synthesis of 1,2,3-triazole with cheaply available Cu(OAc)₂ without any additional reducing agents is ­explored, which provides an exclusive 1,4-regioselectivity at ­ambient conditions in an environmentally benign solvent - water.

Cu(II) catalyst - regioselective - 1,2,3-triazole - water

References and Notes

<A NAME="RD31805ST-1">1</A> Sheldon RA. Green Chem.  2005,  7:  267 

<A NAME="RD31805ST-2">2</A> Cornils B. Herrmann WA. Aqueous Phase Organometallic Catalysis - Concepts and Applications   Wiley-VCH; Weinheim: 1998. 

<A NAME="RD31805ST-3A">3a</A> Leitner W. Top. Curr. Chem.  1999,  206:  107 

<A NAME="RD31805ST-3B">3b</A> Leitner W. Acc. Chem. Res.  2002,  35:  746 

<A NAME="RD31805ST-3C">3c</A> Beckman EJ. J. Supercrit. Fluids  2004,  28:  121 

<A NAME="RD31805ST-4A">4a</A> Sheldon RA. Chem. Commun.  2001,  2399 

<A NAME="RD31805ST-4B">4b</A> Wasserscheid P. Keim W. Angew. Chem. Int. Ed.  2000,  39:  3772 

<A NAME="RD31805ST-4C">4c</A> Dupont J. de Souza RF. Suarez PAZ. Chem. Rev.  2002,  102:  3667 

<A NAME="RD31805ST-4D">4d</A> Song CE. Chem. Commun.  2004,  1033 

<A NAME="RD31805ST-5A">5a</A> Haimov A. Neumann R. Chem. Commun.  2002,  876 

<A NAME="RD31805ST-5B">5b</A> Alper H. Januszkiewicz K. Smith DJH. Tetrahedron Lett.  1985,  26:  2263 

<A NAME="RD31805ST-5C">5c</A> Chanrasekhar S. Narsihmulu C. Sultana SS. Reddy NR. Org. Lett.  2002,  4:  4399 

<A NAME="RD31805ST-6">6</A> Dobbs AP. Rimberley MR. J. Fluorine Chem.  2002,  118:  3 

<A NAME="RD31805ST-7">7</A> Li CJ. Chem. Rev.  2005,  105:  3095 

<A NAME="RD31805ST-8">8</A> Huisgen R. In 1,3-Dipolar Cycloaddition Chemistry   Wiley; New York: 1984.  p.1-176  

<A NAME="RD31805ST-9A">9a</A> Fan WQ. Katritzky AR. In Comprehensive Heterocyclic Chemistry II   Vol. 4:  Katritzky AR. Rees CW. Scriven EFV. Elsevier Science; Oxford: 1996.  p.1-126  

<A NAME="RD31805ST-9B">9b</A> Holla BS. Mahalinga M. Karthikeyan MS. Poojary B. Akberali PM. Kumari NS. Eur. J. Med. Chem.  2005,  40:  1173 

<A NAME="RD31805ST-9C">9c</A> Elmorsi MA. Hassanein AM. Corros. Sci.  1999,  41:  2337 

<A NAME="RD31805ST-9D">9d</A> Kim DK. Kim J. Park HJ. Bioorg. Med. Chem. Lett.  2004,  14:  2401 

<A NAME="RD31805ST-10">10</A> Rostovtsev VV. Green LG. Fokin VV. Sharpless KB. Angew. Chem. Int. Ed.  2002,  41:  2596 

<A NAME="RD31805ST-11">11</A> Kolb HC. Sharpless KB. Drug Discov. Today  2003,  8:  1128 

<A NAME="RD31805ST-12">12</A> Himo F. Lovell T. Hilgraf R. Rostovtsev VV. Noodleman L. Sharpless KB. Fokin VV. J. Am. Chem. Soc.  2005,  127:  210 

<A NAME="RD31805ST-13">13</A> Yamamoto Y. Hayashi H. Saigoku T. Nishiyama H. J. Am. Chem. Soc.  2005,  127:  10804 

<A NAME="RD31805ST-14">14</A> Ye MC. Zhou J. Huang ZZ. Tang Y. Chem. Commun.  2003,  2554 

<A NAME="RD31805ST-15">15</A> Park SB. Alper H. Chem. Commun.  2005,  1315 

<A NAME="RD31805ST-16">16</A>

Typical Procedure for the Synthesis of 1,2,3-Triazoles
To the stirred solution of alkyne (1.2 mmol) and copper catalyst (20 mol%) in H₂O (3 mL), was added alkyl azide (1.0 mmol) in one portion at r.t. After 20 h of stirring, the precipitated product was extracted with EtOAc (3 × 5 mL) and the organic extract was dried. The crude product was subjected to column chromatography to yield the desired product. The products were characterized by ¹H NMR.
Compound 1a: ¹H NMR (CDCl₃): δ = 5.55 (s, 2 H), 7.25-7.37 (m, 8 H), 7.58 (s, 1 H), 7.75 (d, 2 H, J = 8.30 Hz). Compound 2a: ¹H NMR (CDCl₃): δ = 2.36 (s, 3 H), 5.55 (s, 2 H), 7.14-7.37 (m, 7 H), 7.55 (s, 1 H), 7.64 (d, 2 H, J = 8.3 Hz). Compound 3a: ¹H NMR (CDCl₃): δ = 3.83 (s, 3 H), 5.52 (s, 2 H), 6.69 (m, 1 H), 7.19-7.38 (m, 8 H), 7.58 (s, 1 H). Compound 4a: ¹H NMR (CDCl₃): δ = 3.12 (br, 1 H), 4.69 (s, 2 H), 5.48 (s, 2 H), 7.18-7.38 (m, 6 H). Compound 5a: ¹H NMR (CDCl₃): δ = 1.52 (s, 6 H), 4.20 (br, 1 H), 5.39 (s, 2 H), 7.21-7.36 (m, 6 H). Compound 6a: ¹H NMR (CDCl₃): δ = 1.90 (s, 3 H), 2.93 (br, 1 H), 5.43 (s, 2 H), 7.15-7.42 (m, 11 H).