A fully continuous-flow diazotization–hydrolysis protocol has been developed for the preparation of p-cresol. This process started from the diazotization of p-toluidine to form diazonium intermediate. The reaction was then quenched by urea and subsequently followed by a hydrolysis to give the final product p-cresol. Three types of byproducts were initially found in this reaction sequence. After an optimization of reaction conditions (based on impurity analysis), side reactions were eminently inhibited, and a total yield up to 91% were ultimately obtained with a productivity of 388 g/h. The continuous-flow methodology was used to avoid accumulation of the highly energetic and potentially explosive diazonium salt to realize the safe preparation for p-cresol.

中文翻译：

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对甲酚合成的全连续流工艺：杂质分析和工艺优化

已经开发出用于制备对甲酚的全连续流重氮化水解方案。该过程从对甲苯胺的重氮化开始以形成重氮中间体。然后将反应用尿素淬灭，随后水解，得到最终产物对甲酚。在该反应序列中最初发现了三种类型的副产物。在优化反应条件后（基于杂质分析），显着抑制了副反应，最终以388 g / h的生产率获得了最高91％的总收率。使用连续流方法避免了高能且可能爆炸的重氮盐的积累，从而实现了安全的制备方法。对甲酚。