Synthesis And Properties Of Coumarin Schiff Base Derivatives

Coumarin is a structural unit commonly found in many natural active products in nature.Coumarin compounds not only have extensive and significant biological activity,but also possess excellent optical properties,and have high bioavailability and special mechanism of action.At the same time,they have the characteristics of small molecular weight,variable structure,and easy synthesis.They have been widely used in the fields of medicine,agriculture,dyes,organic photoelectric materials,and so on,and have received constant attention from many researchers.Schiff bases and their metal complexes also have a variety of physiological activities and nonlinear optical properties,and they have low toxicity and wide application.They have broad application prospects in many fields such as medicine,catalysis,materials and analytical chemistry.Based on the excellent bioactivity and luminescence properties of coumarin compounds,according to the principle of drug combination in drug design,we introduced the Schiff base group on the coumarin skeleton,expecting to obtain a large amount of both coumarin and the properties of the coumarin derivatives with Schiff base structure of various characteristics are studied,and then new lead compounds with higher biological activity,superior optical properties,and promising development are screened out,in medicine,dyes,organic photoelectric materials,analysis and detection are applied.Based on the previous work and literature research,this study designed the readily available 2,3,4-trimethoxybenzaldehyde as a raw material,through selective demethylation,Knoevenagel,hydrolysis and condensation and other multi-step reactions.Eight novel coumarin Schiff base derivatives were synthesized,and their in vitro antioxidant activity,metal ion fluorescence probe selectivity and coordination performance were studied.The main contents are as follows:1.In recent years,the bioactivities,synthesis methods and fluorescence probes of coumarins were reviewed.The progress of Schiff bases and their complexes were introduced.2.Using 2,3,4-trimethoxybenzaldehyde as raw material,eight coumarin derivatives with Schiff base structure were synthesized via demethylation,Knoevenagel condensation,hydrolysis and nucleophilic addition reaction.The structure was characterized by means of MS,IR and other methods.No new reports have been published on the eight new compounds.3.The antioxidant properties of the synthesized target compounds5a-5h were studied.Using ascorbic acid as a control,the target compounds and their parent compound 4 were determined,and the activities of DPPH free radical,ABTS free radical and hydroxyl free radical were eliminated,and the semi-inhibitory concentration IC₅₀0 was used to evaluate the antioxidant activity.The experimental results showed that in the DPPH free radical scavenging activity test,some of the target compounds showed stronger antioxidant activity than the reference substance,and 60%of the derivatives activity were stronger than its parent,indicating that the introduction of the Schiff base functional group improves the derivatization.The elimination of DPPH free radical activity is advantageous;In the ABTS radical scavenging experiment,the scavenging activity of the parent compound 4 and 50%of the target compound is stronger than the control,but the majority of the derivatives have less activity than the parent compound,indicating that the introduction of basic group into the ABTS radical scavenging activity is insufficient,while the presence of amino group 3 in the coumarin parent seems to play an important role in the removal of ABTS radicals,pending further research and more data support;In the hydroxyl radical scavenging experiments,the antioxidant activity of most of the coumarin Schiff base derivatives were better than that of the control and the mother,demonstrating that the derivatization of the coumarin parent can improve its scavenging activity of the hydroxyl radical.By analyzing the results of three free radical scavenging experiments,it was found that compounds 5h and 5e have stronger scavenging activity on three kinds of free radicals than the reference substance,showing excellent antioxidant activity and possessing the potential value of development and application research.In addition,three substituents?5b,5c,5h?are attached to the aromatic ring of the three Schiff bases,and the 5h is connected to the aromatic ring with an electron-withdrawing nitro group and a hydroxyl group in the meta-position.Antioxidant activity is the strongest,superior to the hydroxyl group in the ortho position and attached to the electron donating 5b and 5c,estimated that the ortho-position phenolic hydroxyl group and the nitrogen atom form a hydroxyl group;there are three substituents attached to the aromatic ring of the Schiff base fragment.Derivatives?5a,5f,5g?,which are connected to the imino group,are o-nitrophenyl,p-nitrophenyl,p-dimethylaminophenyl,respectively,but the worst antioxidant activity is electron donation.The 5a of the dimethylamino group indicates that the presence of electron-withdrawing groups in this class of derivatives is stronger than that of the electron donating group,which is also consistent with our previous findings.A preliminary structure-activity analysis revealed that the target compounds with strong antioxidant activity have the following structural characteristics:?1?It has phenolic hydroxyl groups and exists in free form;?2?Contains a five-member aromatic heterocyclic structure;?3?The electron-withdrawing groups on the aromatic ring show better antioxidant activity than the electron donating group.4.The selective investigation of the metal cations and coordination of the target compounds 5a-5h were carried out to screen the fluorescent probes that can selectively identify metal cations and provide reference data for the study of the coordination mechanism.It was found that both compounds 5b and 5c can selectively recognize Cu²⁺.With the addition of Cu²⁺,the fluorescence intensity is significantly reduced,and it can be used as potential fluorescence quenching Cu²⁺fluorescent probes for further study.Both the fluorescence titration experiments and the Job's spot curves of compounds 5b and 5c showed that the coordination ratio of compounds 5b and 5c to Cu²⁺was 1:1.We believe that the above two compounds have potential application value in the detection of Cu²⁺and can be applied in medical science,biology and environment.At the same time,it can provide reference for the design and synthesis of Cu²⁺fluorescent probes.