Conjugate Hydrocyanation of Aromatic Enones Using Potassium Hexacyanoferrate(II) as an Eco-Friendly Cyanide Source

Abstract

A selective conjugate hydrocyanation of aromatic enones by a one-pot, two-step procedure using potassium hexacyanoferrate(II) as an original eco-friendly cyanide source, potassium hydroxide as a base, and benzoyl chloride as a promoter was described. This protocol has the advantages of a nontoxic cyanide source, high yield, and simple workup procedure.

Key words

conjugate hydrocyanation - 1,4-addition - aromatic enone - green chemistry - nucleophilic addition - potassium hexacyanoferrate(II)

• References and Notes

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• 12 The analytical data for the isolated representative acyl cyanides are given below. Benzoyl Cyanide White solid. IR (KBr): 2224 (CN), 1679 (C=O) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 8.15–8.13 (m, 2 H), 7.82–7.78 (m, 1 H), 7.63–7.59 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 167.8, 136.8, 133.2, 130.4, 129.5, 112.6.
• 13 General Procedure The mixture of K₄[Fe(CN)₆] (0.4 mmol) and benzoyl chloride (2 mmol) was heated at 160 °C for 3 h, then the reaction system was cooled to 40 °C, and aromatic enone (1.5 mmol) in MeCN (5 mL) and KOH (2.4 mmol) in H₂O (3 mL) were added. The mixture was further stirred at 40 °C for the appropriate time indicated in Table 4. After completion of the reaction, monitored by TLC, the resulting mixture was filtered to remove the solids, and the filtrate was concentrated and isolated by column chromatography using PE–EtOAc (10:1) as eluent to give the pure product. The analytical data for representative products are shown below. 4-Oxo-2,4-diphenylbutanenitrile (Table 4, Entry 1) White solid; mp 120–122 °C. IR (KBr): 1681 (C=O), 2238 (CN) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 3.51 (dd, 1 H, J = 5.6, 18.0 Hz, CHCH _aHCO), 3.74 (dd, 1 H, J = 7.6, 18.0 Hz, CHCH _bHCO), 4.58 (dd, J = 6.0, 6.4 Hz, 1 H, ArCHCH₂), 7.26–7.43 (m, 7 H, ArH), 7.58–7.62 (m, 1 H, ArH), 7.92–7.94 (m, 2 H, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 31.9, 44.5, 120.6, 127.5, 128.1, 128.4, 128.8, 129.3, 133.9, 135.2, 135.6 194.6 ppm. Anal. Calcd for C₁₆H₁₃NO (235.28): C, 81.68; H, 5.57; N, 5.95. Found: C, 81.59; H, 5.56; N, 5.97. 4-(4-Methoxyphenyl)-4-oxo-2-phenylbutanenitrile (Table 4, Entry 3) Oil. IR (KBr): 1676 (C=O), 2243 (CN) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 3.37 (dd, J = 6.0, 17.6 Hz, 1 H, CHCH _aHCO), 3.60 (dd, J = 8.4, 17.6 Hz, 1 H, CHCH _bHCO), 3.79 (s, 3 H, CH₃), 4.49 (dd, J = 6.0, 8.0 Hz, 1 H, ArCHCH₂), 6.85 (d, J = 6.8 Hz, 2 H, ArH), 7.23–7.37 (m, 5 H, ArH), 7.83 (d, J = 6.8 Hz, 2 H, ArH) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 31.9, 44.1, 55.5, 113.9, 120.8, 127.4, 128.3, 128.7, 129.2, 130.4, 135.4, 164.0, 193.0 ppm. Anal. Calcd for C₁₇H₁₅NO₂ (265.31): C, 76.96; H, 5.70; N, 5.28. Found: C, 76.80; H, 5.71; N, 5.30.