Study On The Synthesis Of ?-chlorovinyl Ketones With Benzoyl Hydrazines?Hydrazine Monohydrates And Salicylicaldehyde Hydrazones

Heterocyclic compounds are a class of organic compounds that contain a heterocyclic structure in the molecular skeleton and are by far the largest branch of organic compound systems.There are many types of heteroatoms involved in forming heterocycles,among which O,N and S are the most common,and nitrogen-containing heterocycles are widely used in the development and application of new materials and pharmaceuticals.Hetreocyclic compounds are widely existed in nature for their excellent properties and special structures.High efficiency,high regioselective,and atom economy are always the goal of current organic chemists.A large number of literatures have been reported on the synthesis methodology of nitrogen-containing heterocyclic compounds,but most of them have the characteristics of difficult to obtain reaction raw materials,high required temperature,and unfriendly environment.In this paper,we attempt to develop a facile synthesis of nitrogen-containing heterocyclic skeletons via base-promoted annulation of readily available?-chlorovinyl ketones with benzohydrazides,hydrazine hydrate,and salicylic aldehyde hydrazones under extremely mild reaction conditions.A series of experiments were conducted and the details are summaries as follows:The synthesis of 1-acyl-5-hydroxypyrazoline by using?-chlorovinyl ketones and benzohydrazide has been explored in the presence of DABCO at room temperature.The mechanism studies illustrate that the conjugate addition of benzohydrazide to intermidate allenone generated from dehydrochlorination of?-chlorovinyl ketones,followed by a sequential cyclization/isomerization to get 1-acyl-5-hydroxypyrazoline.The formation of 3,5-disubstituted pyrazoles using?-chlorovinyl ketones and hydrazine hydrate was then explored.Two plausible pathways to account for the formation of 3,5-disubstituted pyrazoles are demonstrated.A direct 1,4-conjugate addition of hydrazine to?-chlorovinyl ketones followed by consecutive elimination/cyclization/dehydration process ispossible.Another method is also capable of obtaining 3,5-disubstituted pyrazoles via a dehydrochlorination/conjugate addition/cyclization/dehydration/aromatization sequence in the presence of DABCO.The utility of 1-acyl-5-hydroxypyrazoline is further illustrated by the concise synthesis of 1-acyl pyrazole via BF₃·Et₂O catalyzed dehydration and the formation of 3-pentyl-5-phenyl-1H-pyrazole through BF₃·Et₂O promoted dehydration and debenzoylation.The synthesis of N-monosubstituted salicylic aldehyde hydrazones by using?-chlorovinyl ketones and salicylic aldehyde hydrazones was investigated.The reaction proceeded quickly under mild basic conditions and gave the functionalized salicylic aldehyde hydrazones in high yields via direct Michael addition.