A three-component synthetic method for the efficient preparation of (Z)-N-vinyl ring N,O-acetal derivatives under continuous flow technology was developed. Recently, the continuous flow technology applied in organic synthesis has attracted significant attention, and become useful alternatives to the conventional operations. Furthermore, advances in the translation from ‘‘batch’’ to continuous ‘‘flow’’ mode have expanded rapidly, offering valuable opportunities for a variety of research areas. By using cheap and readily available chemicals as the reaction's starting material, continuous flow synthesis technology has the advantages of excellent reaction process control, high surface area volume ratio, efficient heat exchange, effective mixing, reduced reaction time, and so on. The controllable series cyclization reaction takes place in continuous flow, which precisely regulates the reaction of o-hydroxybenzylamine with aldehydes to form a Schiff base intermediate. Then the intermediate is discharged in time and undergoes an oxa-Michael addition reaction with diethyl acetylenedicarboxylate under base conditions. It experiences a unique intramolecular rearrangement process to form C—O and C—N bonds. In continuous flow synthesis, amines and aldehydes are mixed in tube A and diethyl acetylenedicarboxylate is placed in tube B. First, the mixture of tube A is injected into the first plastic coil reactor in heating bath (HB1), 80 ℃ kept for 10 min. The mixture is transported to the next step and mixed with diethyl acetylene dicarboxylate from tube B in a small T-shaped mixer, injected into the second glass column reactor (HB2), 80 ℃ retained for 40 min. Finally, the nitrogen-, oxygen-containing six-membered ring or seven-membered ring heterocyclics were precisely synthesized with high selectivity, and the two-step synthesis takes only 50 min. The application of continuous flow synthesis technology can avoid the problems involving incomplete reaction of two-component, more side reactions, and provides an alternative method for assembling multi- component with high selectivity and high yield (up to 96%), providing a reference for the high-value conversion of chemical raw materials.

Key words: ring N,O-acetal, continuous flow synthesis technology, high selectivity, atom economy, green chemistry