Telescoped Continuous Flow Synthesis of 2-Substituted 1,4-Benzoquinones via Oxidative Dearomatisation of para-Substituted Phenols Using Singlet Oxygen in Supercritical CO₂

Abstract

This paper describes a continuous multi-step synthesis in supercritical CO₂. A continuous flow synthesis of 2-substituted 1,4-benzoquinones is reported, and details of the high-pressure reactors are given. This proceeds via the telescoped dearomatisation of p-substituted phenols using singlet oxygen in supercritical CO₂ and an acid-mediated C–C migration. The process has a short residence time of 30 minutes, with overall yields and projected productivities of up to 83% and 9 g/day, respectively. This methodology enables a safe and efficient synthesis of 2-substituted 1,4-benzoquinones from photo-generated singlet oxygen, and cheap and readily available p-substituted phenols. The procedure has high atom efficiency, low photocatalyst loading, and substitutes potentially hazardous and corrosive reagents and solvents for molecular oxygen, CO₂, and the less hazardous solid-supported acid Amberlyst-15.

Key words

singlet oxygen - photooxidation - continuous flow - supercritical CO₂ - telescoped synthesis - dearomatization - para-substituted phenols - 1,4-benzoquinones

Publication History

Received: 24 January 2022

Accepted after revision: 28 February 2022

Article published online:
12 May 2022

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