Study Of Hydration And Cyclization Of Methylene Malonitrile Compounds

Benzene,furan,pyridine,pyrimidine structures are often important for compounds which have pharmacological activities.Therefore,these structures are of great significance in the field of medicine.Cyanamide structure plays an important role in antibacterial and antiviral compounds,which means it also has a profound influence on the structure-activity relationship of medicines.Methylenemalononitrile compounds,a simple and readily available reaction substrate,can reacet with a variety of different compounds to construct benzene,furan,pyridine,and pyrimidine through cyclization.It can also construct cyanamide structure through monohydration.So,Methylenemalononitrile compounds has become an important compound studied in recent years.In addition,with the development of metal catalysis,photocatalysis and other methods,a variety of different synthesis strategies have been used for the cyclization and monohydration of methylenemalonitrile compounds.Therefore,the optimization of existing reactions and the development of new methods have become the current research directions of chemists.In the second chapter,the synthesis of cyanamide skeleton by monohydration of methylene malonitrile was studied.With the catalysis of 2.5 mol%Pd?OAc?₂,methylenemalonitriles gave monohydration product in HCOOH solvent and room temperature with high yield.The reaction was efficient with mild condition.The study of compatibility proved that when the methylene malonitrile was monosubstituted by benzene ring?including non-substituted benzene and substituted benzene?,pentacyclic heterocyclic,olefin or alkane,the reaction could complet in 10 min giving corresponding monohydrolysis product with high yield?57-92%?.The reaction produced high stereoselectivity with trans configurations of all all products,which is confirmed by nuclear magnetic resonance.Disubstrated methylenemalonitriles needed a little longer reaction time but the yield is high?45-89%?.The reaction was of high compatibility.In the third chapter,the cyclochemical reactions of methylenemalonitriles were studied.First of all,we developed an arylation of methylenemalonitriles with nitromethane to construct dicyanoaniline.In the presence of 2-equivalent 4-pyrrolidine,the monosubstituted methylene malonitrile derivatives reacted at 40^oC in acetonitrile solvent to produce symmetric dicyanoaniline with various substituents.The method is simple with easy substrate and high yield?up to 92%?.Then,we developed a photocatalyzed reaction of salicylaldehyde with malononitrile to construct polysubstituted benzopyran ring.In this reaction,the conditions and mechanism have been tried and verified,and certain results have been achieved,but further identification and the expansion of substrates are still in progress.