Abstract:

Methyl p-methoxybenzoate, a critical intermediate in fragrance and anticancer drug synthesis, has attracted significant attention for its efficient and green preparation. To address the limitations of conventional multi-step methods, such as the use of corrosive strong acids and the generation of multiple byproducts, this study developed a novel visible-light-driven one-step synthesis protocol. Utilizing an acridinium salt as the photocatalyst and methanol as both the solvent and nucleophilic reagent, the target product was efficiently synthesized via a photoinduced radical relay mechanism under aerobic conditions. Experimental results demonstrated a 90% yield after 3h of reaction at room temperature with the yield remaining above 78% in gram-scale amplification experiments. Comparative analysis highlighted the superior advantages of this approach: a one-step esterification process that eliminated traditional separation procedures; a mild reaction system free from strong acids and noble metals, ensuring excellent equipment compatibility; significantly enhanced atom economy and aligning with environmentally friendly catalytic principles. This strategy was extendable to the synthesis of various substituted aromatic esters, offering an efficient and scalable green methodology for the production of fragrance and anticancer drug intermediates.

Key words: visible-light photocatalysis, p-methoxybenzaldehyde, methyl p-methoxybenzoate, pharmaceutical intermediates, gram-scale synthesis

摘要：

对甲氧基苯甲酸甲酯作为香料和抗癌药物的关键中间体，其高效绿色合成备受关注。针对传统多步法存在的强酸腐蚀、副产物多等问题，本文开发了一种可见光驱动的对甲氧基苯甲醛一步合成对甲氧基苯甲酸甲酯新方法。以吖啶盐为光催化剂，甲醇既作溶剂又作亲核试剂，在空气氛围中通过光诱导自由基接力机制，实现对甲氧基苯甲酸甲酯的高效合成。实验表明，室温反应3h即可获得90%收率。工艺经实验室克级放大实验，产率保持在78%以上。通过对比分析，本方法优势显著：一步高效酯化，避免传统分离流程；无强酸/贵金属参与，体系温和且设备兼容性优异；原子经济性显著提升，符合环境友好型催化理念。该策略可拓展至多种取代芳香酯的合成，为香料及抗癌药物中间体的绿色制备提供了高效、可放大的新方案。

关键词: 可见光催化, 对甲氧基苯甲醛, 对甲氧基苯甲酸甲酯, 药物中间体, 克级合成