One-Step Synthesis of Nitriles from Acids, Esters and Amides Using DIBAL-H and Ammonium Chloride

Abstract

A convenient, one-step procedure is presented for the conversion of carboxylic acids or their derivatives (esters, lactones, amides) to nitriles with an aminoalane reagent prepared from diisobutylaluminum hydride (DIBAL-H) and ammonium chloride.

Key words

nitrile - carboxylic acid - diisobutylaluminum hydride - aluminum amide - ammonium chloride

• References and Notes

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• 17 Experimental Procedure for the Preparation of Aminoalane Reagent: A solution of DIBAL-H in toluene (1 M, 1 equiv) was added to a cooled (0–5 °C) suspension of NH₄Cl (1.05 equiv) in anhyd THF under argon. The reaction was stirred for 15 min in an ice bath and then for 1.5 h at r.t. After this time, the obtained complex solution was used directly for nitrile synthesis.
• 18 Experimental Procedure for the Synthesis of Nitrile from Carboxylic Acid, Ester, Lactone or Amide: The solution of aminoalane reagent (prepared from 20 equiv of DIBAL-H in case of ester and lactone substrates or from 40 equiv in case of carboxylic acid and amide substrates) was added to a solution of carboxylic acid (1 equiv) or its derivative (lactone, ester or amide, 1 equiv) in anhyd THF at r.t. Stirring was continued for 16 h at 66 °C. After this time, the reaction mixture was cooled, quenched with aqueous solution of KHSO₄ and the product was extracted with CHCl₃. The extract was washed with H₂O, dried over anhyd Na₂SO₄, and the solvent was evaporated. The crude product was purified by silica gel chromatography with hexane–EtOAc elution.