2-氟-5-甲氧基苯甲醛的合成

Synthesis of 2-Fluoro-5-methoxybenzaldehyde

以4-氟-3-甲基苯胺为原料,经重氮化、甲基化和溴化、水解等四步反应合成2-氟-5-甲氧基苯甲醛,产物的含量为99.176%(HPLC),总摩尔产率约37%,产物结构通过了1 H NMR和MS的验证。其中,重氮化酸性水解反应的最佳条件为n(4-氟-3-甲基苯胺)∶n(水)∶n(磷酸)∶n(五水硫酸铜)=1∶30∶4.0∶1.1,甲基化反应的最佳反应条件为n(4-氟-3-甲基苯酚)∶n(硫酸二甲酯)=1∶1.3,NaOH水溶液的质量浓度为20%,反应时间约为10h。该法具有生产成本低、反应条件温和、易于工业化生产等优点。

2-Fluoro-5-methoxyformaldehyde was synthesized from 4-fluoro-3-methylaniline by diazotization,methylation,bromination and hydrolysis.The product content was 99.176%（by HPLC）,and the total molar yield was 37%.The structure of the product was confirmed by 1 H NMR and MS.The optimal conditions of the hydrolysis reaction of the diazotization reaction stage were：n（4-fluoro-3-methylaniline）∶n（water）= 1∶30,n（4-fluoro-3-methylaniline）∶n（phosphoric acid）= 1∶4.0,and n（4-fluoro-3-methylaniline）∶n（copper sulfate pentahydrate）= 1∶1.1.The optimal conditions of methylation were n（4-fluoro-3-methylphenol）∶n（dimethyl sulfate）= 1∶1.3,the concentration of NaOH was 20%,and the reaction time was 10 h.This method has low cost and mild reaction conditions and is suitable for production in industrial scale.