Acceptorless Dehydrogenation under Neat Reaction Conditions: Synthesis of 2-Aryl/Alkyl Quinazolinones Using Supported Ni NPs as Catalyst

Abstract

We report here a Ni-NPs-catalyzed one-pot synthesis of 2-alkyl/aryl quinazolinone motifs via acceptorless dehydrogenation of alcohol, condensation of an aldehyde intermediate with 2-aminobenzamide, followed by a second dehydrogenation of the cyclized intermediate. The protocol is atom-economical and require earth-abundant Ni as the catalyst. The present report involves the annulation of 2-aminobenzamide with various types of primary alcohols, including aryl/heteroaryl methanol, and aliphatic alcohols, and produces high yields of the desired products under neat conditions. The catalyst was synthesized via a high-temperature pyrolysis strategy, using ZIF-8 as the sacrificial template. The Ni NPs@N-C catalyst was characterized by XPS, HR-TEM, HAADF-STEM, XRD, and ICP-MS. The catalyst is stable even in air at room temperature and displayed excellent activity in the acceptorless dehydrogenative coupling synthesis of quinazolinones and could be recycled five times without appreciable loss of its activity.

Key words

acceptorless dehydrogenation - alkyl/aryl quinazolinone - nitrogen-doped carbon - Ni nanoparticles - solvent-free protocol

Publication History

Received: 22 June 2024

Accepted after revision: 15 August 2024

Accepted Manuscript online:
15 August 2024

Article published online:
18 September 2024

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• 35 Synthesis of Ni Nanoparticles on Nitrogen-Doped Carbon (Ni NPs @N-C) Solution A was prepared by dissolving zinc nitrate hexahydrate (24 mmol) and nickel nitrate hexahydrate as Ni precursor (7.5 mmol) in 120 mL water. Similarly, solution B was prepared by dissolving 2-methyl imidazole (90 mmol) in 60 mL water. Thereafter, solution A was tardily poured into solution B with constant stirring for 10 h at room temperature. Over time the formation of a bright bluish-green precipitate of Ni@ZIF-8 was observed. The Ni@ZIF-8 precipitate was then collected by centrifugation, washed with water (30 mL × 3), and dried at 70 °C for 4 h to obtain a fine pale-bluish green powder. Then the obtained powder of Ni@ZIF-8 was transferred into a quartz tube and heated to 900 °C for 2 h with a heating rate of 5 °C min^–1 under an argon atmosphere. After naturally reaching room temperature, the obtained black powder was stirred with 0.5 M sulfuric acid at 80 °C for 10 h and further washed with deionized water thrice (20 mL × 3 each). The obtained solid was dried in the oven at 80 °C and further subjected to heating at 900 °C (with a heating rate of 5 °C min^–1) under an argon atmosphere for 2 h to generate the desired catalyst Ni nanoparticles on nitrogen-doped carbon (Ni NPs @N-C). One-Pot Synthesis of 2-Phenyl Quinazolinone via Acceptorless Dehydrogenation Using Ni NPs @N-C Catalyst 2-Aminobenzamide (0.50 mmol), benzyl alcohol (1.5 mmol), Cs₂CO₃ (0.1 mmol, 20 mol%), and Ni NPs @N-C (10 mg, Ni content: 0. 252 wt%) were charged in an oven-dried reaction vessel, flushed with argon gas and maintained the inert atmosphere using an argon balloon. The reaction was carried out on a preheated heating block (heating block temperature 150 °C) and stirred for 24 h (monitored by TLC). After the completion of the reaction, the reaction mixture was quenched with EtOAc and filtered through a Celite bed, the filtrate was evaporated to dryness using a rotary evaporator to obtain the crude product. The crude product was further purified by column chromatography using an EtOAc–hexane solvent mixture (10:90). The same procedure was followed for all other substrates in Table 2. 2-Phenylquinazolin-4(3H)-one (Table [2], Entry 3a) White solid; yield 92%; R_f = 0.5, hexane/ethyl acetate = 90:10, v/v. ¹H NMR (500 MHz, CDCl₃): δ = 11.72 (s, 1 H), 8.33 (d, J = 7.8 Hz, 1 H), 8.29 (t, J = 3.55 Hz, 2 H), 7.90–7.77 (m, 2 H), 7.64–7.57 (m, 3 H), 7.51 (t, J = 7.2 Hz, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 163.94, 151.76, 149.51, 134.89, 132.80, 131.63, 129.02, 127.99, 127.41, 126.78, 126.34, 120.81. 7-Methyl-2-(thiophen-2-yl)quinazolin-4(3H)-one (Table [2], Entry 3n) Yellow solid; yield 68%; R_f = 0.5, hexane/ethyl acetate = 85:15, v/v. ¹H NMR (500 MHz, CDCl₃): δ = 11.76 (s, 1 H), 8.21 (d, J = 8.2 Hz, 1 H), 8.15 (dd, J = 4.0, 1.2 Hz, 1 H), 7.61–7.57 (m, 2 H), 7.32–7.29 (m, 1 H), 7.25–7.22 (m, 1 H), 2.52 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 163.45, 149.56, 147.28, 146.08, 137.58, 131.16, 128.36, 128.20, 128.05, 127.43, 126.27, 118.27, 21.96. HRMS (ESI) m/z [M + H⁺] calcd for C₁₂H₉N₂OS: 243.0592; found: 243.0587. 2-Hexyl-7-methylquinazolin-4(3H)-one (Table [2], Entry 3o) White solid; yield 80%; R_f = 0.5, hexane/ethyl acetate = 85:15, v/v. ¹H NMR (500 MHz, CDCl₃): δ = 11.43 (s, 1 H), 8.15 (d, J = 8.1 Hz, 1 H), 7.49 (d, J = 0.6 Hz, 1 H), 7.28 (dd, J = 8.0, 1.4 Hz, 1 H), 2.89–2.71 (m, 2 H), 2.50 (s, 3 H), 1.90–1.80 (m, 2 H), 1.50–1.40 (m, 2 H), 1.37–1.29 (m, 4 H), 0.98–0.82 (m, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 163.89, 156.89, 149.52, 145.81, 127.91, 126.93, 126.01, 118.07, 35.96, 31.43, 28.87, 27.48, 22.45, 21.97, 14.03. HRMS (ESI): m/z [M + H⁺] calcd for C₁₅H₂₀N₂O: 245.1654; found: 245.1653.