Fischer indole synthesis in DMSO/AcOH/H₂O under continuous flow conditions

A new continuous flow synthetic method for preparing indole and its derivatives are successfully developed to overcome the disadvantages of traditional batch methods, such as low conversion rates, long reaction times, and amplification effects. The method represents a sustainable and efficient preparation of indole and its derivatives without the need for additional catalysts. By investigating the effects of the reaction temperature, the solvent, the equivalence ratio, and the residence time, high conversion rates and excellent yields were simultaneously achieved within 20 min under optimized conditions. For the template reaction, DMSO/H₂O/AcOH = 2:1:1 is used as the solvent, the reaction temperature is 110 °C, and the ratio of phenylhydrazine hydrochloride to cyclopentanone is 1:1.05. Indole and a wide array of its derivatives are synthesized to verify the universality of the method, and most of the reactions exhibit satisfactory conversion rates and high yields are obtained. This new continuous flow method is more suitable for industrial scale-up relative to traditional batch methods.