Synthesis And Properties Of Substituted Nitrogen (oxygen) Heterocycles And Their Iron (tin) Derivative

Xanthone,cinnoline and coumarin are the heterocyclic compounds which have various biological activities of antibacterial,antiviral,antioxidant,anticoagulant and anticarcinogen and excellent photophysical properties.Ferrocene has inherent stability,excellent redox properties,and low toxicity.Organotin compounds have good biological activity and structural diversity.Both of them have become ideal materials for the development of metal drugs and have attracted much attention.By combining ferrocene,organotin active groups with xanthone,cinnoline,coumarin compounds,novel molecular functional materials with excellent structure and properties are expected to be obtained.A simple method was developed for the preparation of fluoro-xanthone,cinnoline,coumarin and ferrocene acrylic acid compounds.The active metal groups,ferrocene and organotin,were introduced into the heterocyclic molecules by substitution reactions.More than 150 new compounds were synthesized and characterized,and the X-ray single crystal structures of more than 80 compounds were determined.The photophysical properties,anticancer activity and electrochemical properties of the compounds were studied.A series of fluoroxanthone compounds were synthesized by a three-step reaction of esterification,Fries rearrangement and intramolecular nucleophilic substitution using fluorobenzoyl chloride and substituted phenol as raw material.In Fries rearrangement,o-hydroxyfluorophenone were obtained with high yields（>80%）by using Na Cl as dispersant at～180℃,reducing carbonization at high temperature.The substitution reactions of 7-methyl-2,3,4-trifluoro-9H-xanthone with nitrogen,oxygen and sulfur nucleophilic reagents were studied,and 11 xanthone derivatives with selective substitution of the 3-position fluorine atom were obtained.Photophysical properties of representative compounds have been studied.The results show that 7-hydroxyxanthone and 3-aminoxanthone emit strong blue fluorescence in acetonitrile.Xanthone synthesized as rigid skeleton plane molecules arranged in parallel in crystals withπ-πpacking and C-H…F,C-H…O weak interactions.By the diazotization of ethyl 2,3,4,5-tetrafluorobenzoyl acetate with arylamine and the subsequent nucleophilic substitution reaction,more than 40 diazotization products and 40 cinnoline derivatives were synthesized.The single crystal structures of 1-phenylmiso-linone compounds have been measured for the first time.When CH₃COONa is used as base,the diazotization products can be successfully cyclized into cinnoline compounds,while the intramolecular continuous cyclization occured to form phenoxazine and oxazepino compounds using K₂CO₃ as base,achieving selective synthesis,which provides a simple method for the construction of polycyclic compounds.The test of photophysical properties shows that there is a maximum absorption at～390 nm in UV and a maximum emission at～450 nm in fluorescence spectrum.Four organotin complexes were obtained by the reaction of 1-phenyl-7-ethoxy-4-oxy-6,8-difluoro-1,4-dihydromiso-3-carboxylic acid with organotin chloride（or oxide）showing good anticancer activity(A549:IC₅₀～0.4μM;HeLa:IC₅₀～1.4μM).The dibutyltin complex is a centrosymmetric tetra-tin core trapezoidal dimer,and the tributyltin complex is a one-dimensional chain structure.In the presence of triethylamine,the coumarin-hydrazone organotin complexes were obtained by the reaction of 4-hydroxy-3-acyl-6,7,8-trifluorocoumarin which were hydrolyzed by chromone,organotin chloride and hydrazide.The three active functional groups of coumarin,ferrocene and organotin co-existed in the same molecule through the acylhydrazone.Bioactivity tests showed that they had good anticancer activity(A549:IC₅₀～0.16μM;HeLa:IC₅₀～0.58μM).Except for tin complexes of ferrocenylhydrazone,other complexes have strong yellow-green fluorescence.Ferrocoumarin compounds have good redox properties.A simple method for the synthesis of（E）-3-ferrocenyl-3-substituted acrylic acid has been developed.Under the catalysis of DCC and DMAP,3-ferrocenyl acrylic acid was esterified with 7-hydroxy-coumarin to produce coumarin acrylates.In K₂CO₃-CH₃COCH₃ solution,the substitution of the neighboring fluorine atom of（E）-3-（2,3,4,5-tetrafluorophenyl）-3-diferrocenyl-2-propenoic acid by carboxy oxygen gave rise to the lactone 6,7,8-trifluoro-7-diferrocenyl coumarin,providing a new method for the synthesis of 4-ferrocenyl coumarin.In this work,the facile synthesis of fluorinated xanthone,cinnoline and coumarin was explored and a library of small molecule compounds were constructed of fluorinated xanthone,cinnoline and coumarin.The fluorescence and anticancer properties of these compounds were studied.These results enriched the content of xanthone,cinnoline and coumarin compounds,and laid the foundation for further study of their structure-property relationship and development of their applications.