Structure,Propertie And Interaction On Acyl Thiourea Derivatives Of Fluorine And Chloride Substituted Aniline

The 14 fluorine and chlorine substituted acyl thiourea derivatives were synthesized by phase transfer catalysis in this paper.Except for compound VIII,no other substances have been reported in the literature.The structures were characterized including elemental analysis,infrared spectroscopy,nuclear magnetic 1H and 13C spectra,and X-ray single crystal diffraction techniques,and 10 single crystal structures were obtained.The details are as follows:Crystal:Group one:? N-(4-methylbenzoyl)-N'-(2,3-difluorophenyl)thiourea? N-(3-methylbenzoyl)-N'-(2,3-difluorophenyl)thiourea? N-(3-methylbenzoyl)-N'-(2,3,4-trifluorophenyl)thiourea? N-(2-methylbenzoyl)-N'-(2,3,4-trifluorophenyl)thiourea? N-(3-methoxybenzoyl)-N'-(2,3-difluorophenyl)thioureaGroup two:? N-(4-methylbenzoyl)-N'-(4-chloro-3-trifluoromethylphenyl)thiourea? N-(4-methylbenzoyl)-N'-(4-chloro-3-trifluoromethylphenyl)thiourea? N-(2-methylbenzoyl)-N'-(4-chloro-3-trifluoromethylphenyl)thiourea?? N-(4-chlorobenzoyl)-N'-(4-chloro-3-trifluoromethylphenyl)thiourea?? N-(4-bromobenzoyl)-N'-(4-chloro-3-trifluoromethylphenyl)thioureaPowder:Group one:? N-(2-methylbenzoyl)-N'-(2,3-difluorophenyl)thiourea? N-(4-chlorobenzoyl)-N'-(2,3-difluorophenyl)thiourea? N-(4-chlorobenzoyl)-N'-(2,3-dimethylphenyl)thioureaGroup two:? N-(4-fluorobenzoyl)-N'-(4-chloro-3-trifluoromethylphenyl)thioureaFrom the obtained single crystal structures,we analyzed structural parameters,conformation of the central group(-CO-NH-CS-NH-),spatial packing modes and intermolecular interaction for the acyl thiourea derivatives.Hirshfeld surface analysis and two-dimensional fingerprints were introduced to further study the weak interactions among thiourea molecules.The results showed that C-H…S,N-H…S and C-H…F hydrogen bonds and ?-? stacking are found in the thiourea derivatives,in addition to the H…H,C…H,C…S,F…C1,and C1…H Weak interactions.These weak interactions can significantly increase the antifungal activity of the acylthiourea derivatives.On the other hand,substances with good antifungal and antitumor activities were screened by mycelial growth rate method and molecular docking technique.For the 14 acyl thiourea derivatives,the effects of substituents and positions of the benzene ring on antifungal activity were investigated.The results showed that the introduction of fluorine atom on the benzene ring can effectively enhance the antifungal activity,and the activity was higher when the fluorine atom and the chlorine atom simultaneously present in the aroyl thiourea derivative.Molecular docking analysis showed that the C=O,N-H groups and halogen F atom in the thiourea compound act as acceptors or donors forming hydrogen bonds with different amino acid residues respectively,which helps to enhance affinity for the drug and receptor macromolecules.The above conclusions provided reference for the mechanism of drug inhibition,and also provided new ideas for the design of new drugs.