Efficient Method to Synthesize Benzhydrazides by In Situ Oxidation/Coupling of Benzylic Alcohols with Azodicarboxylates

Abstract

An efficient synthesis of benzhydrazides has been achieved through the direct acylation of azodicarboxylates with benzylic alcohols in moderate to high yields. The method represents the first practical approach to amides containing a hydrazine structural unit from benzylic alcohols.

Key words:

benzhydrazides - hydroacylation - azodicarboxylates - C–N bond formation

• References and Notes

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• 15 Dialkyl 1-Aroylhydrazine-1,2-dicarboxylates; General Procedure
  The appropriate dialkyl azodicarboxylate (1.5 mmol) was added to a stirred mixture of CuO nanoparticles (10 mol%) and a benzylic alcohol (0.75 mmol) in MeCN (0.5 mL) under argon. A 30% solution of t-BuOOH (2 equiv) was added dropwise, and the mixture was stirred at 80 °C for 6 h. When the benzaldehyde generated in situ had been consumed (TLC; decolorization of the azodicarboxylate was also observed), the mixture was treated with NaBH₄ (0.5 mmol, 20 mg) in MeOH (0.5 mL). After 5 min, the reaction was quenched with aq NH₄Cl (1 mL) and brine (1 mL). The cooled mixture was centrifuged to separate the catalyst then extracted with EtOAc (2 × 20 mL). The extracts were dried (MgSO₄), filtered, and concentrated in vacuo to give a crude product that was purified by column chromatography [silica gel, EtOAc–hexanes (1:4)]. Diisopropyl 1-Benzoylhydrazine-1,2-dicarboxylate White solid; yield: 85%; mp 123 °C. ¹H NMR (500 MHz, CDCl₃): δ = 7.7 (m, 2 H), 7.52 (t, J = 7.4 Hz, 1 H), 7.4–7.45 (m, 2 H), 7.26 (br s, 1 H), 4.98–5.05 (m, 1 H), 4.8–4.9 (m, 1 H), 1.29 (d, J = 6.0 Hz, 6 H), 1.08 (d, J = 5.4 Hz, 6 H). Diethyl 1-Benzoylhydrazine-1,2-dicarboxylate Colorless oil; yield: 80%. ¹H NMR (500 MHz, CDCl₃): δ = 7.68 (d, J = 7.2 Hz, 2 H), 7.30–7.50 (m, 3 H), 7.24 (br s, 1 H), 4.23 (q, J = 7.2 Hz, 2 H), 4.15 (q, J = 7.2 Hz, 2 H), 1.29 (t, J = 7.2 Hz, 3 H), 1.07 (t, J = 7.2 Hz, 3 H).