Studies On The Synthesis And Bioactivity Of Benzoxazaphosphinine Derivatives

Organophosphorus pesticide is an important class of pesticides, which plays animportant role in agriculture production and the protection of the agriculture products.However, with the increasing requirement of improving the environment, some highly toxicorganophosphorus pesticides will be faced with the inhibition use. Hence, the development ofhigh efficiency, low toxicity, high selectivity, high safety, environment compatibility andnovel green organophosphorus pesticides have received increasing attention. Recently,3,4-dihygro-2H-benzo[e][1,3,2]oxazaphosphinine2-oxides as a novel class of heterocycliccompounds containing nitrogen, oxygen and phosphorus atoms have attracted great interest indrug research because of their broad biological activities, and also become one of the hotpoint in the development of new organophosphorus pesticides.This paper mainly studied on the synthesis and bioactivity of3,4-dihydro-2H-benzo[e][1,3,2]oxazaphosphinine2-oxides. Twenty six target compounds of3-aryl-2-ethoxy/phenoxy-3,4-dihydro-2H-benzo[e][1,3,2]oxazaphosphinine2-oxides36a-36zand ten3-methoxycarbonyl-3,4-dihydro-2H-benzo[e][1,3,2]oxazaphosphinine2-oxides37a-37j and twelve3-aryl-2-aryloxy-3,4-dihydro-2H-benzo[e][1,3,2]oxazaphosphinine2-oxides38a-38l were synthesized. All the structures of the target compounds werecharacterized by IR,¹H NMR and¹³C NMR, and some of which characterized by ESI-MS.Few representative compounds were characterized by X-ray. It was also investigated thebioactivities of all target compounds.（1） The synthesis of raw materials and intermediates. A series of2-（aminomethyl）phenols40a-40y were synthesized by “one-pot” method. Twenty compounds40a-40t were prepared by reducing the intermediate Schiff bases with NaBH4withoutseparation. The intermediate Schiff bases were generated by reaction of substituted salicylalswith arylamine under solvent-free condition. This procedure has the advantages of simpleoperation, high productivity, short reaction time. Compounds40u-40y were prepared by thereactions of substituted salicylals with glycine methyl ester hydrochloride in dry ethanolgiving the corresponding Schiff bases follwoed by reduction with NaBH4. In general,reactions under solvent-free condition gave products in higher yields than those in solvent.（2） The synthesis of target compounds. Twenty six compounds of3-aryl-2-ethoxy/phenoxy-3,4-dihydro-2H-benzo[e][1,3,2]oxazaphosphinine2-oxides36a-36zwere synthesized from the reactions of2-（aminomethyl）phenols40a-40t with dichlorophosphates in the presence of triethylamine. Likewise, ten target compounds3-methoxycarbonyl-3,4-dihydro-2H-benzo[e][1,3,2]oxazaphosphinine2-oxides37a-37j weresynthesized from the reactions of2-（aminomethyl）phenols40u-40y with dichlorophosphatesin the presence of triethylamine. Finally, twelve2-aryloxy-3-aryl-3,4-dihydro-2H-benzo[e][1,3,2]oxazaphosphinine2-oxides38a-38l weresynthesized from the reactions of2-（aminomethyl）phenols with phosphorus oxytrichloride.All the reactions gave high trans selectivity, i.e. the substituent at2-position of the ring istrans to the substituent at3-position.（3） Three single crystals of compounds36s,38i and40s were cultivated by slowlyevaporating the solvent, and their crystal structures were determined and analyzed by X-raydiffraction.（4） The insecticidal activities of all target compounds36a-36z,37a-37j and38a-38lwere evluated, and the preliminary bioassay showed that the target compounds exhibited thehighest activity against Mythimna sepatara, wherein the insecticidal activity of the compound36o up to100%, and85%for compound38k. In addition to compounds of36g, the targetcompounds exhibited good insecticidal activity against Aphis fabae as shown by compound36n（82.92%）. The fungicidal activities of compounds36a-36u,37a-37j and38（a-d, f-i, k-l）were assayed, and the preliminary bioassay showed that the activities of componds36a-36uare higher than compounds37a-37j and38（a-d, f-i, k-l）. Moreover, the target compoundsexhibited the best fungicidal activitie against Sclerotonia sclerotiorum. Compound36lexhibited87.9%inhibition activity, and76.5%for compound36u.