Continuous-Flow Synthesis of <i>meta</i>-Substituted Phenol Derivatives

Abstract

Two complementary microreactor technologies were developed for the study of biphasic gas–liquid reactions and preparation of meta-substituted phenol derivatives. The first capillary microreactor, composed of a T-junction and simple capillary, enabled oxidative Heck/dehydrogenation on a microgram scale with a shortened reaction time; the total sequence time for oxidative Heck/dehydrogenation reactions was optimized from 2160 min in a traditional batch system to 130 min in the microchemical system. The second tube-in-tube microreactor, composed of a gas-permeable inner tube and gas-nonpermeable outer tube, successfully performed a gram-scale synthesis under the optimized safety and economic conditions which were established from the first microgram-scale study. The two microreactors have great potential for exploring reactions involving gaseous and liquid reagents.