Cyanide-Free Cyanation of Aryl Iodides with Nitromethane by Using an Amphiphilic Polymer-Supported Palladium Catalyst

Dedicated to Professor Benjamin List in celebration of his Nobel Prize in Chemistry 2021

Abstract

A cyanide-free aromatic cyanation was developed that uses nitromethane as a cyanide source in water with an amphiphilic polystyrene–poly(ethylene glycol) resin-supported palladium catalyst and an alkyl halide (1-iodobutane). The cyanation proceeds through the palladium-catalyzed cross-coupling of an aryl halide with nitromethane, followed by transformation of the resultant (nitromethyl)arene intermediate into a nitrile by 1-iodobutane.

Key words

cyanation - nitromethane - cross-coupling - palladium catalysis - aqueous medium - catalyst support

Publication History

Received: 08 September 2021

Accepted: 20 October 2021

Accepted Manuscript online:
20 October 2021

Article published online:
16 November 2021

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• 26 Naphthalene-1-carbonitrile (4a) [CAS Reg. No. 86-53-3] Typical Procedure (Table 1Entry 8): To a mixture of polymeric catalyst 1 (74 mg; 0.02 mmol Pd), Cs₂CO₃ (260 mg, 0.8 mmol), TBAF (104 mg, 0.4 mmol), 1-iodobutane (147 mg, 0.8 mmol), and 1-iodonaphthalene (2a; 102 mg, 0.4 mmol) in water (0.8 mL) was added nitromethane (73.2 mg, 1.2 mmol). The resulting mixture was stirred at 100 °C for 24 h, then cooled and filtered. The polymeric resin beads were rinsed successively with EtOAc (3 × 3 mL) and H₂O (3 × 3 mL), and the recovered catalyst beads were used in subsequent recycling runs. The combined filtrates and washings were extracted with MTBE; ICP-OES analysis demonstrated that the extracts were not contaminated with leached Pd species (ICP-OES analysis: detection limit of Pd = 10 ng/mL). The extracts were then washed with brine, dried (MgSO₄), and concentrated in vacuo. The crude residue was purified by chromatography [silica gel, hexane–EtOAc (4:1)] to give a colorless oil; yield: 55 mg (90%). 1H NMR (400 MHz, CDCl3): δ = 8.25 (d, J = 8.2 Hz, 1 H), 8.09 (d, J = 8.2 Hz, 1 H), 7.95-7.92 (m, 2 H), 7.71 (td, J = 7.7, 1.2 Hz, 1 H), 7.63 (td, J = 7.5, 1.4 Hz, 1 H), 7.54 (dd, J = 8.2, 7.3 Hz, 1 H): 13C NMR (101 MHz, CDCl3): δ = 133.44, 133.08, 132.80, 132.52, 128.80, 128.76, 127.71, 125.32, 125.08, 117.97, 110.35.Naphthalene-2-carbonitrile (4b) [CAS Reg. No. 613-46-7]White solid; yield 31 mg (51%).1H NMR (400 MHz, CDCl3): δ = 8.25 (s, 1 H), 7.94-7.89 (m, 3 H), 7.67-7.59 (m, 3 H): 13C NMR (101 MHz, CDCl3): δ = 134.79, 134.32, 132.39, 129.35, 129.19, 128.56, 128.20, 127.80, 126.50, 119.40, 109.52.Phenanthrene-9-carbonitrile (4c) [CAS Reg. No. 2510-55-6]White solid; yield: 71 mg (88%). 1H NMR (400 MHz, CDCl3): δ = 8.75-8.71 (m, 2 H), 8.34-8.31 (m, 1 H), 8.28 (s, 1 H), 7.97-7.95 (m, 1 H), 7.82-7.77 (m, 3 H), 7.72-7.68 (m, 1 H): 13C NMR (101 MHz, CDCl3): δ = 135.83, 131.95, 130.19, 129.99, 129.95, 129.67, 129.03, 128.38, 128.27, 127.80, 126.28, 123.25, 123.03, 118.09, 109.58.