Studies On The Green Synthesis And Antifungal Activitity Of Phosphinyl Or Benzothiazole Derivatives

As an important part of the means of production,pesticides have made great contributions in ensuring food production and improving crop quality.In recent years,due to increasing concerns on the environmental protection,the pursuit of high quality life,and the requirements of sustainable development,the development of green pesticides is a significant goal of human society as well as an urgent and challenging task.The research and development of green pesticides mainly includes two aspects:green products and green processes for the preparation of pesticides.As a class of clean energy,visible light is characterized by the ready availability,abundance,and non-pollution.Photocatalytic organic reactions have recently attracted considerable attention,which has become one of the research hotspots.Given its great advantages over conventional methods,it can be anticipated that photocatalytic strategies will have great potential applications in the research and development of new pesticides.Organophosphorus and heterocyclic compounds play an important role in the development of pesticides,such as marketed pesticides ditalimfos,boscalid,thiabendazole,and ethaboxam,etc.The marketed pesticides fosthiazate and dufulin,containing both phosphinyl oxide and thiazole structures,have good insecticidal activities.In order to explore the bioactive groups and select the lead compounds with potential activities,as well as to meet the requirements of green,environmental protection,economy,and sustainable development posed by the research and development of new pesticides,this paper have designed and synthesized a variety of phosphorus-containing organic compounds and novel benzothiazole derivatives bearing a hydroxyl group or a chlorine atom by employing visible-light photoredox catalyzed olefin difunctionalization or visible light photoredox catalyzed decarboxylation/heteroaryl migration strategy,in which air,water,and lithium chloride(LiCl)have been used as oxygen,hydroxyl,and chlorine sources,respectively.Furthermore,antifungal activity test has been conducted for all the synthetic target compounds.The details are summarized as follows:Part Ⅰ:Visible light-promoted oxidative phosphinylation of olefins for the synthesis ofβ-ketophosphinyl derivativesβ-Ketophosphinyl derivatives play an important role in drug chemistry,organic synthesis,life sciences,and functional materials.With air as the green oxidant and oxygen source,the first visible-light-driven aerobic oxyphosphorylation of olefins has been developed under metal-free and mild reaction conditions,providing a direct and efficient access to β-ketophosphinyl derivatives in high yields.20 compounds were synthesized,of which one was unreported compound.The products were well characterized by NMR(1H NMR,13C NMR,and 31P NMR)and high-resolution mass spectrometry(HRMS).Part Ⅱ:Photocatalytic decarboxylation/heteroaryl migration/remote hydroxylation for the synthesis of benzothiazole derivativesThiazoles,an important class of heterocyclic compounds,are prevalent in many pesticides,medicines,and materials.By the combination of visible-light photoredox catalyzed group migration and remote functionalization strategies,a highly efficient decarboxylation/heteroatyl migration/remote hydroxylation reaction,for the first time,has been achieved with N-(acyloxy)phthalimides as the starting materails and H2O as the safe,eco-friendly,and cost-effective hydroxyl source.The optimal reaction conditions were established by the screening of reaction parameters,such as catalysts,additives,and solvents.A series of novel hydroxyl-featured heterocycle products(24 examples)can be obtained in moderate to good yields with high chemoselectivities and regioselectivities.The products were characterized by NMR(1H NMR,13C NMR),HRMS,melting point,and single-crystal X-ray diffraction analysis.A possible reaction mechanism photocatalysis decarboxylation/heterocycle migration/remote hydroxylation was proposed based on literature reports,control experiments,radical-trapping,and isotope labeling experiments.Part Ⅲ:Photocatalytic decarboxylation/heteroaryl migration/remote chlorination for the synthesis of benzothiazole derivativesOrganic photosensitizers,common photocatalysts used in organic reactions,are generally inexpensive and readily available.By combining visible light photoredox catalysis with group migration strategy,sequential photocatalytic decarboxylation/heteroaryl migration/remote chlorination reaction has been realized,providing the corresponding chloro-substituted benzothiazole products(19 examples),whose structures are new and have not been reported before.All obtained new compounds were characterized by NMR and HRMS.The method features the use of simple and cheap lithium chloride(LiCl)as chlorine source,mild and transition-metal-free conditions,no extra acid or base additives,and broad substrate scope.Part Ⅳ:Antifungal activity of synthetic derivativesThe in-vitro antifungal activities of all 63 synthetic compounds against Rhizoctonia solani,Fusarium graminearum,Alternaria mali,Botrytis cinerea,Alternaria solani,and Colletrichum orbiculare were tested by growth rate method.At the concentration of 50μg/mL,all the target compounds showed different degrees of inhibitory activity.Based on the results,the relationship between structure and activity was discussed,and compounds with higher activity were selected for toxicity determination.The EC50 value of A2,B1,B3,B4,B10,B11,B13,B14,B15,B16,B19,C8,C11,C13,C15,and C18 against Rhizoctonia solani were 29.68,24.09,25.31,34.37,18.43,23.13,9.39,28.50,10.19,8.43,9.35,48.77,24.29,47.81,24.88,and 25.40 μg/mL,respectively.The EC50 values of B1,B4,and B13 against Botrytis cinerea,were 35.27,38.15,and 35.65 μg/mL.The antifungal activities of β-ketophosphinyl derivatives were not as good as that of benzothiazole derivatives,but still had antifungal activity against Rhizoctonia solani,Fusarium graminearum,Alternaria mali,Botrytis cinerea,and Colletrichum orbiculare except Alternaria solani.The hydroxyl-featured benzothiazole derivatives with dimethyl substitution on the benzene ring(B13)or dimethyl substitution at the alkyl chain(B18)or chlorine substitution on the heterocycle moiety(B19)show good antifungal activities.In summary,with visible-light photoredox catalyzed olefin functionalization or visible-light photoredox catalyzed group migration and remote functionalization strategies,a variety of phosphinyl or benzothiazole derivatives bearing important functional groups(63 examples in all,of which 44 were unreported compounds)have been synthesized under mild and green conditions.In the methods,air,water,and lithium chloride were used as the oxygen source,hydroxyl source,and chlorine source,respectively.Antifungal activity studies have shown that some compounds have good inhibitory activity against the tested fungi.It is anticipated that the present green methods and the related results have potential applications for the discovery of lead compounds as well as new fungicides.