Synlett 2008(13): 2072-2074  
DOI: 10.1055/s-2008-1077979
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Direct Synthesis of Acyl Azides from Carboxylic Acids by the Combination of Trichloroacetonitrile, Triphenylphosphine and Sodium Azide

Joong-Gon Kima, Doo Ok Jang*b
a Biotechnology Division, Hanwha Chemical R&D Center, Daejeon 305-345, Korea
b Department of Chemistry, Yonsei University, Wonju 220-710, Korea
Fax: +82(33)7602182; e-Mail: dojang@yonsei.ac.kr;
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Publikationsverlauf

Received 26 April 2008
Publikationsdatum:
15. Juli 2008 (online)

Abstract

Various carboxylic acids were converted into acyl azides in excellent yields by treating with trichloroacetonitrile, triphen­ylphosphine and sodium azide at room temperature. The reaction was applicable to the preparation of dipeptide without rearrangement.

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Typical Experimental Procedure: To a mixture of benzoic acid (122 mg, 1.0 mmol), triphenylphosphine (525 mg, 2.0 mmol) and sodium azide (78 mg, 1.2 mmol) in anhyd acetone (2 mL) under argon was added trichloroacetonitrile (0.2 mL, 2.0 mmol) dropwise at r.t. The reactants were allowed to react for 30 min. After concentration of the reaction mixture by a rotary evaporator, the residue was then diluted with CH2Cl2 (4 mL), and washed with H2O (2 mL). The organic layer was dried over anhyd MgSO4. After filtration, the solvent was removed and the residue was purified by column chromatography on silica gel (hexanes-EtOAc, 2:1) to give benzoyl azide (141 mg, 96%).

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N-Fmoc-l-Ala-N3: mp 162-164 ˚C (lit.¹7 mp 162 ˚C); [α]D ²5 16.3 (c = 1, CHCl3) (lit.¹7 [α]D -16). ¹H NMR (300 MHz, CDCl3): δ = 1.41 (d, J = 2.2 Hz, 3 H), 3.86 (m, 1 H), 4.22 (t, J = 2.3 Hz, 1 H), 4.41 (d, J = 2.3 Hz, 2 H), 5.28 (s, 1 H), 7.22-7.84 (m, 8 H).

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N-Fmoc-Ala-Leu-OMe: mp 124-126 ˚C (lit.²c mp 123-126 ˚C); [α]D ²5 -28.1 (c = 1, CHCl3) (lit.²c [α]D -25.2). ¹H NMR (300 MHz, CDCl3): δ = 0.92 (s, 6 H), 1.42 (d, J = 2.2 Hz, 3 H), 1.55 (m, 1 H), 1.64 (m, 2 H), 3.71 (s, 3 H), 4.23 (t, J = 2.4 Hz, 1 H), 4.30 (t, J = 2.2 Hz, 1 H), 4.40 (d, J = 2.4 Hz, 2 H), 4.61 (q, J = 1.6 Hz, 1 H), 5.42 (s, 1 H), 6.37 (s, 1 H), 7.25-7.82 (m, 8 H).