An Efficient Synthesis of 2,4,6-Triarylpyridines by Use of Benzyl Halides under Neat Conditions

Abstract

An efficient synthesis of 2,4,6-triarylpyridines is described. Heating a mixture of an acetophenone, a benzyl halide, and ammonium acetate under neat conditions afforded the corresponding Kröhnke pyridines in excellent yields.

Key words

2,4,6-triarylpyridines - Kröhnke pyridines - acetophenones - benzyl halides - heterocycles - cyclizations

• References and Notes

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• 17 General Procedure for the Preparation of 2,4,6-Triarylpyridines 3a–r, Exemplified with Compound 3a A mixture of acetophenone (1 mmol), benzyl chloride (2 mmol), and NH₄OAc (3 mmol) in a 5 mL round-bottomed flask was magnetically stirred at 150 °C for 8 h. Progress of the reaction was followed by TLC monitoring. The reaction mixture was cooled to ambient temperature, H₂O (2.5 mL) was added, and the product was extracted into CH₂Cl₂ (2 × 2.5 mL). The combined organic phases were dried over Na₂SO₄, filtered, the solvent was removed, and the residue was purified by crystallization from absolute EtOH. TAP 3b,c,k–m were purified by column chromatography using n-hexane–EtOAc (6:1) as eluent. The solvent was removed, and the solid residue was recrystallized from absolute EtOH. 2,4,6-Triphenylpyridine (3a) Yield 0.116 g (97%, in respect to acetophenone); colorless crystals; mp 135–136 °C (136–137 °C).^{18a 1}H NMR (500.1 MHz, CDCl₃): δ = 7.40–7.60 (m, 9 H, 9 × CH), 7.78 (d, J = 8.0 Hz, 2 H, 2 × CH), 7.92 (s, 2 H, 2 × CH), 8.23 (d, J = 8.0 Hz, 4 H, 4 × CH). ¹³C NMR (125.8 MHz, CDCl₃): δ = 117.2 (CH), 127.2 (CH), 127.3 (CH), 128.8 (CH), 129.0 (C), 129.1 (CH), 129.2 (CH), 139.1 (C), 139.6 (CH), 150.2 (C), 157.5 (C). 4-(4-Methoxyphenyl)-2,6-diphenylpyridine (3c) Yield 0.104 g (87%, in respect to acetophenone); colorless crystals; mp 100–101 °C (99–100 °C).^{18a 1}H NMR (500.1 MHz, CDCl₃): δ = 3.87 (s, 3 H, OCH₃), 7.04 (d, J = 8.7 Hz, 2 H, 2 × CH), 7.44 (t, J = 7.2 Hz, 2 H, 2 × CH), 7.52 (t, J = 7.7 Hz, 4 H, 4 × CH), 7.70 (d, J = 8.7 Hz, 2 H, 2 × CH), 7.85 (s, 2 H, 2 × CH), 8.20 (d, J = 7.2 Hz, 4 H, 4 × CH). ¹³C NMR (125.8 MHz, CDCl₃): δ = 55.4 (OCH₃), 114.5 (CH), 116.6 (CH), 127.1 (CH), 128.3 (CH), 128.6 (CH), 129.0 (CH), 131.2 (C), 139.6 (C), 149.6 (C), 157.4 (C), 160.5 (C).
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