Study On Knoevenagel Condensation In Water Medium And Biginelli Reaction Under Solvent-free

The thesis is composed of two parts:In the first part, the Knoevenagel condensations are reported in water medium without adding any catalyst. The research conclusions are as follows:The Knoevenagel condensations of various carbonyl compounds with active methylene compounds are reported in water medium. Seventeen reported and eight novel methyl-enemalononitrile derivatives were synthesized by the condensations. The structures of the obtained methylenemalononitrile derivatives were confirmed by spectral characterization and elemental analyses. The crystal structures of two arylidenemalononitriles have been determined by single-crystal X-ray diffraction. The possible mechanism of the condensation of carbonyl compound with active methylene compound in water medium was proposed. The condensation of aromatic aldehydes with active methylene compounds has been found to proceed very efficiently at room temperature giving excellent yields, but the condensation of heteroaromatic,α,β-unsaturated and aliphatic aldehydes with active methylene compounds proceeded smoothly at 50-65℃with good yields and the reactions of aromatic, aliphatic ketones as well as p-phthalaldehyde with malononitrile also proceeded at 75～85℃with moderate yields. The work-up procedure is very simple, efficient and environmental-friendly.The reactions of aromatic aldehydes with barbituric acid, N-phenyl barbituric acid or 2-thiobarbituric acid were also reported in water medium without adding any catalyst. Forteen novel and ten reported 5-arylidene barbituric acids were synthesized by the condensation of aromatic aldehydes with barbituric acid or N-phenylbarbituric acid. The structures of the obtained 5-arylidene barbituric acids were confirmed by spectral characterization and elemental analyses. The condensation of various aldehydes such as aromatic, heteroaromatic,α,β-unsaturated aldehydes and p-phthalaldehyde with barbituric acid and the condensation of N-phenylbarbituric acid with aromatic aldehydes bearing electron-doner groups have been found to proceed very efficiently at room temperature giving excellent yields, but the condensation of barbituric acid with o-substituted aromatic aldehydes or o-phthalaldehyde and the condensation of N-phenylbarbituric acid with aromatic aldehydes bearing electron-drawing groups proceeded smoothly at 50～60℃with good yields. The condensation and Michael addition reactions of aromatic aldehydes with 2-thiobarbituric acid afforded 5-arylidene thiobarbituric acids and bis(6-hydroxy) pyrimidinone derivatives at 70～80℃. However, treatment of salicylaldehyde or substituted salicylaldehydes with barbituric acid or thiobarbituric acid afforded ten chromeno[2,3-d] pyrimidinones at 50～90℃in water without adding any catalyst. The structures of the products were characterized by elemental analysis, IR,1H NMR,13C NMR. The crystal structure of one chromeno [2,3-d]pyrimidinone has been determined by single-crystal X-ray diffraction. The possible mechanisms of the formation the bis(6-hydroxy) pyrimidinone and chromeno [2,3-d] pyrimidinone were proposed. The study provides a simple, efficient and environmental-friendly method for the synthesis of 5-arylidene barbituric acids and chromeno [2,3-d]pyrimidinones.One-pot three component condensation reactions of aromatic aldehydes, malononitrile, and barbituric acid or 2-thiobarbituric acid were described for the preparation of a series of pyrano[2,3-d]pyrimidine derivatives under ultrasonic irradiation or microwave radiation in aqueous media without adding catalyst. The structures of the products were characterized by IR,1H NMR,13C NMR spectra and elemental analyses. The possible mechanism of the three component condensation of aromatic aldehydes, malononitrile with barbituric acid or 2-thiobarbituric acid in water medium were proposed. The one-pot condensation of aromatic aldehyde with malononitrile and barbituric acid has been found to proceed very efficiently at room temperature giving excellent yields under ultrasonic irradiation, but the condensation ofα,β-unsaturated aldehyde as well as p-phthalaldehyde with malononitrile and barbituric acid also proceeded smoothly at room temperature with good yields. The one-pot condensation of aromatic aldehyde with malononitrile and 2-thiobarbituric acid or barbituric acid has been found to proceed very efficiently giving excellent yields under microwave radiation in 5～15 min. The microwave-assisted method avoided the long reaction time of usual synthesis route, saved the troubles of isolation the intermediate and minimized the environmental loading.In the second part, the Biginelli reactions of salicylaldehyde or substituted salicyl-aldehydes, urea, N-phenylurea or thiourea and active methylene compounds under solvent-free conditions are reported. The research conclusions are as follows:Five novel and five reported Monastrol analogues were synthesized by Biginelli reaction of salicylaldehyde, urea or thiourea and active methylene compounds under solvent-free conditions with NaHSO4 as catalyst in high yields. The structures of the obtained Monastrol analogues were characterized by IR, 1H NMR, 13C NMR and elemental analyses. The crystal structures of two Monastrol analogues have been determined by single-crystal X-ray diffraction. The Biginelli reaction formed two different products, chain or oxygen-bridged Monastrol analogues, depending on the structures of active methylene compounds. The products were caused by steric effects exerted by the alcohol terminus of the ester group in the active methylene component. The possible formation mechanisms of the oxygen-bridged Monastrol analogues were proposed. Previous controversial results as to the structures of the chain Monastrol analogues and oxygen-bridged Monastrol analogues were also discussed.The Biginelli reaction of substituded salicylaldehydes, active methylene compounds like methyl acetoacetate, ethyl acetoacetate, acetylacetone with urea, N-phenylurea or thiourea was further studied under solvent-free conditions with NaHSO4 as catalyst. Forty-one novel chain or oxygen-bridged Monastrol analogues were synthesized by these Biginelli reactions in high yields. The structures of the obtained Monastrol analogues were characterized by IR,1H NMR,13C NMR and elemental analyses. The crystal structures of one Monastrol analogue has been determined by single-crystal X-ray diffraction. These Biginelli reactions formed two different products, chain and oxygen-bridged Monastrol analogues, depending on the structures of active methylene compounds or condensation reagents. The products were caused by steric effects and electronic effects.One-pot three component condensation reactions of methyl acetoacetate, hydroxylamine and aromatic aldehydes were used for the preparation of a series of 3-methyl-4-arylmethylene-isoxazol-5(4H)-one derivatives under ultrasonic irradiation or microwave radiation in aqueous media. The structures of the products were characterized by elemental analysis, IR, 1H NMR and the crystal structures of two 3-methyl-4-arylmethylene-isoxazol-5(4H)-one derivatives have been determined by single-crystal X-ray diffraction. The possible mechanism of the three component condensation reactions of methyl acetoacetate, hydroxylamine and aromatic aldehydes in water medium were proposed. The third component may be aldehydes bearing electron-doner or electron-drawing groups, the one-pot condensation has been found to proceed efficiently in good to medium yields under ultrasonic irradiation or microwave radiation in aqueous media. The condensation of methyl acetoacetate, hydroxylamine withα,β-unsaturated, hetero aromatic aldehydes as well as p-phthalaldehyde also proceeded smoothly in medium yields under above conditions. The work-up procedure is very simple and environmental friendliness.Twenty-four 5-arylidene barbituric acids and eight chromeno[2,3-d]pyrimidinones were valued for their antimicrobial activity against bacterial strands by the agar diffusion method and found to be active against the three test bacterial organisms. The optical properties of one 3-methyl-4-arylmethylene- isoxazol-5(4H)-one derivative have been tested.