| The utilization of pesticides has a long history,during which pesticides have made tremendous contributions to the development of human society.However,the use of pesticides by the ancients was limited to certain natural poisonous plants and minerals.The method was simple but of limited options.It was until the emergence of modern chemical industry that the prelude of large-scale use of pesticides gradually opened.Since the first discovery of an organophosphorus compound with insecticidal activity by German chemist Schrader in 1937,organophosphorus pesticides have been grown dramatically over the past 80 years with more than 300 pesticides developed covering almost all fields of pesticides.Representative species include dichlorphos as insecticides,glyphosate as herbicides,iprobenfos as fungicides and so on.After a brilliant golden period,organophosphorus pesticides also face some problems such as difficulty in creation and drug resistance.In recent years,only a few of new species have appeared on the market.However,organophosphorus pesticides have still attracted much attention of various chemical workers due to their low price,relatively simple production technology,simple molecular structure,easy degradation,distinctive and practical advantages in protecting crops.Viewing from statistics of global new compound patent during 2008-2013,fungicides were the most popular research field.Among organophosphorus pesticides,however,fungicides show relatively fewer research reports compared with insecticides and herbicides.Therefore,it is worthy to develop novel types of organic phosphorus fungicides with great potential and optimistic market value.Our country has a long story of producing and using pesticides,but creation of pesticides still remains at the level of imitating expired patents from foreign countries.After the efforts in "10th Five-Year" period,pesticides with independent intellectual property rights in our country have fulfilled the zero breakthrough and new creation system of pesticide have been established.Despite of these achievements,there still has much work to be done.Based on the application of organophosphorus compounds in the field of organic synthesis,the methods for new pesticides creation and a large amount of literatures,three types of phosphinyl oxide compounds containing conjugated dienes,sulfone group and pyran ring respectively have been developed in this work.Rigorous experiments were performed with detailed data obtained and clear mechanism research clarified.In order to screen out the desired compounds with ideal bactericidal activity,preliminary screening of the biological activity of the synthesized compounds have also been carried out.The details are summarized as follows:Part Ⅰ:Construction of conjugated diene with phosphinyl oxide group through Suzuki coupling reactionConjugated dienes are a type of very important organic synthesis intermediates.The structure is widely found in natural products,medicines,materials,and pesticides.Considering its potential biological activity,palladium-catalyzed Suzuki-Miyaura coupling with α-allenyl ethers as educts has been established and 21 kinds of conjugated diene phosphinyl oxide derivatives were successfully synthesized.The compounds were isolated and characterized by1H NMR,13C NMR,31P NMR and HRMS.All of the 21 compounds are entirely new and have not been reported before.On the basis of the experimental facts and some previous reports,the reaction first goes through the formation of the intermediate containing palladium species,followed by metallization,reductive elimination and eventually gives the desired compounds.Part Ⅱ:Bifunctionalization of hydrazonyl to construct sulfone-containing phosphinyl oxide derivativesSulfone groups as a very important functional group with general reactivity are common motifs in many fine chemicals such as medicines,pesticides,dyes,and materials.The main sulfone sources currently used in the field of organic synthesis include thioethers,sulfonyl halides,sulfinic acid or sulfinic acid salts,sulfonyl hydrazides and so on.Hydrazonyl with a long history in organic synthesis,however,has rarely been applied as a sulfone source.The reports have been mainly focused on the application of the carbene structure,leading to the atom waste.In this work,reactions were designed with hydrazonyl as a sulfone source which provides a one-step synthesis of sulfone-containing phosphinyl oxide when reacted with allenylphosphine oxides.31 kinds of sulfone-containing phosphinyl oxide derivatives were obtained in the presence of a catalytic amount of 1,10-Phen/K2CO3.Through rigorous controlled experiments,it was proposed that three steps were involved in the reaction.The sulfone group takes part in the whole synthesis process in form of free radical and negative ions.The synthesized compounds were isolated and characterized by 1H NMR,13C NMR,31P NMR,HRMS,IR,X-ray and melting point.All of the 31 compounds are new compounds and have not been reported before.Part Ⅲ:[3+3]cycloaddition of β-dicarbonyl compounds to construct pyran-containing phosphinyl oxide derivativesThe pyran ring structure is widely found in the fine chemicals such as natural products,medicines,pesticides,and photosensitive materials,with potential biologically activity.Currently,one of the main methods for the synthesis of pyran ring structures is the use ofβ-dicarbonyl compounds as starting materials.Therefore,in this work,a cost-effective system is revealed to construct pyran-containing phosphinyl oxide derivatives through formal[3+3]cyclization of allenylphosphine oxides and 1,3-diones.27 kinds of pyran-containing phosphinyl oxide derivatives were successfully synthesized.Based on the controlled experiments,it was found that the reaction went through both carbon anion and oxygen anion route,and a possible reaction mechanism was then proposed.The compounds were characterized by 1H NMR,13C NMR,31P NMR,HRMS,NOESY,X-ray and melting point,indicating that the synthesized 27 compounds are all novel compounds and have not been reported in literature.Part Ⅳ:Determination of bactericidal activityAfter characterization of the three types of organophosphorus compounds,the fungicidal of conjugated diene phosphinyl oxide compounds against Botrytis cinerea,Colletrichum orbiculare,Alternaria solani,Fusarium graminearum,Rhizoctonia solani,and Alternaria mali were tested for bactericidal activity;the bactericidal activity of the other two types against Botrytis cinerea,Alternaria solani,Fusarium graminearum,Rhizoctonia solani,Rape sclerotinia rot,and Alternaria mali were also tested.At the concentration of 50 μg/mL,all the target compounds showed different degrees of inhibitory activity.Based on the results of the activity assay,the structure-activity relationship of the target compounds was analyzed,and compounds with higher activity were selected for EC50 determination.The EC50 results of compounds A5,A12,A13,C15,and C20 against Rhizoctonia solani were 15.06 μg/mL,10.83 μg/mL,7.64 μg/mL,22.69 μg/mL,and 25.36 μg/mL,respectively;The EC50 values of compounds B14,B17,B20,C10,C15,C19 and C20 to Rape sclerotinia rot were 7.72 μg/mL,13.52 μg/mL,13.54 μg/mL,4.85 μg/mL,20.05 μg/mL,11.44 μg/mL,and 4.44 μg/mL,respectively.The EC50 of compound C20 against Botrytis cinerea was 25.35 μg/mL.In summary,three novel methods for synthesizing conjugated diene phosphinyl oxide compounds,sulfone-containing phosphinyl oxide compounds,and pyran-containing phosphinyl oxide compounds have been reported respectively.The bactericidal activity of 79 new compounds was measured,with some showing certain activities.It’s worthy of further research on the three kinds of phosphinyl oxide derivativies. |
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