Solvent-Free Pivalic Acid/Copper Chloride Jointly Promoted Chlorination of 1,2,3-Triazoles

Christophe Menendez; Nathalie Saffon; Christian Lherbet; Michel Baltas

doi:10.1055/s-0032-1317446

Synlett, Table of Contents

Synlett 2012; 23(18): 2623-2626
DOI: 10.1055/s-0032-1317446

letter

Solvent-Free Pivalic Acid/Copper Chloride Jointly Promoted Chlorination of 1,2,3-Triazoles

Christophe Menendez

^aCNRS, Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, SPCMIB, UMR-5068, 118 Route de Narbonne, 31062 Toulouse cedex 9, France

^bUniversité de Toulouse, UPS, Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, SPCMIB, 118 route de Narbonne, 31062 Toulouse cedex 9, France

,

Nathalie Saffon

^cUniversité de Toulouse, UPS, and CNRS, ICT FR2599, 118 route de Narbonne, 31062 Toulouse, France Fax: +33(5)61556011 Email: lherbet@chimie.ups-tlse.fr Email: baltas@chimie.ups-tlse.fr

,

Christian Lherbet*

^aCNRS, Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, SPCMIB, UMR-5068, 118 Route de Narbonne, 31062 Toulouse cedex 9, France

^bUniversité de Toulouse, UPS, Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, SPCMIB, 118 route de Narbonne, 31062 Toulouse cedex 9, France

,

Michel Baltas*

^aCNRS, Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, SPCMIB, UMR-5068, 118 Route de Narbonne, 31062 Toulouse cedex 9, France

^bUniversité de Toulouse, UPS, Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, SPCMIB, 118 route de Narbonne, 31062 Toulouse cedex 9, France

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Abstract

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Abstract

A novel chlorination reaction on the 5-position of 1,2,3-triazoles, directly from 5H-substituted 1,2,3-triazoles was developed by using copper(II) chloride in pivalic acid. A series of triazoles were thus chlorinated in low to good yields.

Key words

chlorination - triazole - copper chloride - pivalic acid

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References

References and Notes
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11 Bromination of triazole was also performed with CuBr₂ without success.
12 General procedure: To a solution of triazole (0.3 mmol, 1 equiv) in pivalic acid (500 mg), was added CuCl₂ (1 equiv) at room temperature. The reaction mixture was warmed to 140 °C and stirred under air for 46 h. Pivalic acid was evaporated under reduced pressure and the residue was dissolved in EtOAc. The organic layer was washed with water (3 × 20 mL), dried over MgSO₄, and concentrated under reduced pressure. The residue was purified by flash chromatography. 5-Chloro-4-hexyl-1-phenethyl-1H-1,2,3-triazole (1): Yield: 62%; light-yellow oil; ¹H NMR (CDCl₃): δ = 7.26 (m, 3 H), 7.12 (dd, J = 7.6, 1.8 Hz, 2 H), 4.50 (t, J = 7.5 Hz, 2 H), 319 (t, J = 7.2 Hz, 2 H), 2.62 (t, J = 6.9 Hz, 2 H), 1.67 (m, 2 H), 1.30 (m, 6 H), 0.89 (t, J = 6.7 Hz, 3 H); ¹³C NMR (CDCl₃): δ = 136.7, 128.72, 128.71, 127.0, 49.5, 36.0, 31.5, 28.7, 28.4, 24.5, 22.5, 14.0; HRMS: (DCI/CH₄): m/z calcd for C₁₆H₂₃N₃Cl: 292.1581; found: 292.1605. 1-Benzyl-5-chloro-4-hexyl-1H-1,2,3-triazole (3): Yield: 47%; yellow oil; ¹H NMR (CDCl₃): δ = 7.28 (m, 5 H), 5.48 (s, 2 H), 2.63 (t, J = 7.6 Hz, 2 H), 1.68 (m, 2 H), 1.30 (m, 6 H), 0.86 (t, J = 6.7 Hz, 3 H); ¹³C NMR (CDCl₃): δ = 144.1, 134.1, 128.9, 128.4, 127.7, 122.3, 51.9, 31.4, 28.8, 28.4, 24.6, 22.5, 14.0, HRMS: (DCI/CH₄): m/z calcd for C₁₅H₂₁N₃Cl: 278.1424; found: 278.1415.
13 Crystal data for compound 8a: C₂₂H₃₃Cl₂N₃O₂; M = 442.41; monoclinic; space group P2₁/c; a = 27.1442(7) Å, b = 4.9516(1) Å, c = 17.6348(5) Å, β = 101.803(2)°; V=2320.13(10) Å³; Z = 4; crystal size 0.28 × 0.10 × 0.03 mm³; 26260 reflections collected (5307 independent, R _int =0.0494), 265 parameters, R1 [I>2σ(I)] = 0.0429, wR2 [all data] = 0.1004, largest diff. peak and hole: 0.267 and –0.234 e·Å^–3. CCDC 876301 (8a) contains the supplementary crystallographic data for this Letter. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
14 Yang L, Lu Z, Stahl SS. Chem. Commun. 2009; 6460
15 Crystal data for compound 13: C₁₈H₁₈ClN₃; M = 311.80; monoclinic; space group P 2₁/c; a = 8.7163(11) Å, b = 10.9837(13) Å, c = 17.052(2) Å, β = 98.365(6)°; V = 1615.2(3) Å³; Z = 4; crystal size 0.30 × 0.20 × 0.12 mm³; 24818 reflections collected (3975 independent, R _int = 0.0344), 254 parameters, 225 restraints, R1 [I>2σ(I)]= 0.0515, wR2 [all data] = 0.1599, largest diff. peak and hole: 0.428 and –0.240 e·Å^–3. CCDC 876302 (13) contains the supplementary crystallographic data for this Letter. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif
16 For a review, see: Wendlandt AE, Suess AM, Stahl SS. Angew. Chem. Int. Ed. 2011; 50: 11062
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19 Liégault B, Lapointe D, Caron L, Vlassova A, Fagnou K. J. Org. Chem. 2009; 74: 1826

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