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Synlett 2011(17): 2521-2524  
DOI: 10.1055/s-0030-1260306
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Metal-Free, Aqueous and General Route to 1,5-Disubstituted-1,2,3-triazoles: ‘Reversed Regioisomeric’ 1,3-Dipolar Cycloaddition of Azides and Vinyl Sulfones

Santu Dey, Dhrubajyoti Datta, Tanmaya Pathak*
Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur 721 302, India
Fax: +91(3222)282252; e-Mail: tpathak@chem.iitkgp.ernet.in;
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Publication History

Received 31 May 2011
Publication Date:
13 September 2011 (online)

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Abstract

A metal-free, vinyl sulfone-based synthesis of 1,5-disubstituted-1,2,3-triazoles is reported for the first time. These triazoles are easily formed in a regioselective fashion by heating under reflux a mixture of a substituted vinyl sulfone and an organic azide ‘on water’. This powerful and practical route has the potential to be exploited for the synthesis of complex 1,5-disubstituted-1,2,3-triazoles.

Key words

triazoles - on water - vinyl sulfone - organic azide - click chemistry

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15

For the synthesis of 11k from 5-azido-5-deoxy-2,3-O-isopropylidene-β-d-ribofuranoside, 2 equiv of NaHCO3 was used in the reaction mixture to neutralize the acid generated after elimination. NaHCO3 is not required for the synthesis of 2b-d, 11a-j or 11l-n.

20

General procedure for the synthesis of 1,5-disubstituted-1,2,3-triazoles (2b-d and 11a-n): A mixture of vinyl sulfone 6 or 10 (1 mmol), and azide (1.5 mmol for monoazide and 0.5 mmol for diazide) in water (10 mL/mmol of 6 or 10) was heated at reflux temperature for 3-19 h. After completion of the reaction (monitored by TLC) the reaction mixture was treated with sat. NaHCO3 and the product was extracted with EtOAc (3 × 30 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and the filtrate was evaporated to dryness under reduced pressure. The residue was purified by silica column chromatography to afford the corresponding 1,5-disubstituted-1,2,3-triazoles 2b-d and 11a-n.