Regioselective Synthesis of Functionally Crowded Benzenes at Room Temperature through Ring Transformation of 2H-Pyran-2-ones [1]

Abstract

An expeditious synthesis of highly substituted benzenes with electron-withdrawing or electron-donating substituents is ­described and illustrated by carbanion-induced ring transformation of 2H-pyran-2-one with malononitrile in excellent yield. The ­novelty of the reaction lies in the creation of an aromatic ring at room temperature from a six-membered lactone under mild reaction conditions.

2H-pyran-2-one - benzene - malononitrile - ring transformation reaction

References and Notes

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28

General Procedure for the Synthesis of 5 and 7: A mixture of 5-alkyl-/5,6-dialkyl-3-cyano-4-methylsulfanyl-2H-pyran-2-ones 3 or 6-isopropyl-4-sec-amino-2H-pyran-2-ones 6 (1 mmol), malononitrile (1.2 mmol) and powdered KOH (1.2 mmol) in anhyd DMF (5 mL) was stirred at r.t. for 8-12 h. After completion of the reaction, the reaction mixture was poured into ice-water with vigorous stirring and finally neutralized with dilute HCl. The solid thus obtained was filtered and purified on a neutral alumina column using CHCl₃-hexane (1:9) as eluent. 5a: yield: 89%; white solid; mp 236-238 °C. ¹H NMR (200 MHz, CDCl₃): δ = 2.48 (s, 3 H, Me), 2.54 (s, 3 H, SMe), 5.10 (br s, 2 H, NH₂), 6.42 (s, 1 H, ArH). ¹³C NMR (50.0 MHz, CDCl₃ + DMSO): δ = 19.95, 26.68, 96.73, 98.40, 118.95, 119.83, 120.87, 152.67, 155.72, 158.00. IR (KBr): 2213 (CN), 3353, 3442 (NH₂) cm^-1. MS (FAB): m/z = 204 [M⁺ + 1]. HRMS: m/z calcd for C₁₀H₉N₃S: 203.0532; found: 203.0517. 7a: yield: 86%; white solid; mp 190-192 °C. ¹H NMR (200 MHz, CDCl₃): δ = 1.27 (d, J = 6.8 Hz, 6 H, 2 × Me), 3.15-3.37 (m, 5 H, CH, 2 × CH₂), 3.83-3.91 (m, 4 H, 2 × CH₂), 5.10 (br s, 2 H, NH₂), 6.17 (s, 1 H, ArH). ¹³C NMR (75.5 MHz, CDCl₃): δ = 21.38, 32.24, 49.76, 65.40, 85.02, 87.90, 102.70, 114.73, 115.00, 152.77, 157.62, 157.92. IR (KBr): 2210 (CN), 3353 (NH), 3412 (NH) cm^-1. MS (ESI): m/z = 271 [M⁺ + 1]. HRMS: m/z calcd for C₁₅H₁₈N₄O: 270.1481; found: 270.1483.

29

General Procedure for the Synthesis of 6: A mixture of compound 3d (1.0 mmol) and secondary amine (1.2 mmol) was refluxed in MeOH (20 mL) for 6-8 h. After completion of the reaction, MeOH was evaporated under vacuum, and the reaction mixture was washed with ice-cooled H₂O. The crude was purified on a silica gel column using CHCl₃ as eluent. 6a: yield 74%; white solid; mp 162-164 °C. ¹H NMR (200 MHz, CDCl₃): δ = 1.23 (d, J = 6.8 Hz, 6 H, 2 × Me), 2.00-2.10 (m, 4 H, 2 × CH₂), 2.62-2.73 (m, 1 H, CH), 3.54-3.62 (m, 2 H, CH₂), 4.02-4.10 (m, 2 H, CH₂), 5.71 (s, 1 H, CH). ¹³C NMR (75.5 MHz, CDCl₃): δ = 20.36, 34.00, 49.89, 66.99, 73.24, 94.52, 117.63, 161.92, 163.11, 172.59. IR (KBr): 1704 (CO), 2207 (CN) cm^-1. MS (ESI): m/z = 249 [M⁺ + 1].