Studies On The Synthesis And Bioactivity Of N-Substituted-3,4-Dihydro-Benzo[1,4]Oxazines

Design and development of high efficiency, low toxicity, good selectivity, high safetyand good environmental compatibility of modern “green” chemical pesticides had becomeone of the hot research topics in new pesticides. In recent years,3,4-Dihydro-2H-benzo[1,4]oxazine compounds are new popular nitrogen heterocycliccompounds, having attracted people’s attention in drug research field because of theirbroad biological activities.The paper mainly studied the synthesis and bactericidal activity ofN-substituted-3,4-dihydro-2H-benzo[1,4]oxazines,29novel N-substituted-3,4-dihydro-2H-benzo[1,4]oxazines20a~20o,23a~23c and21a~21k were prepared, and their structureswere characterized by IR、1H NMR and13C NMR, some of them were chareacterized byESI-MS.(1) Using2-aminophenol and substituted benzaldehydes as raw materials,92-(substituted benzylamino)phenols22a~22i were prepared by “one-pot reaction”, theintermediate Schiff bases were synthesized under solvent-free. The method not only hasthe advantages of simple operation, but also has high yield, which is an ideal greensynthesis method for these kinds of compounds.(2)3,4-Dihydro-2H-benzo[1,4]oxazine1was prepared by reaction of2-aminophenoland1,2-dibromoethane. It was investigated the effect of reaction temperature, molar ratioof reactants and reaction time on the yields, and obtained the optimized condition: reactiontemperature being110℃, molar ratio of2-aminophenol and1,2-dibromoethane being1:1.3,and reaction time being10h. Under this optimized condition, the yield of the reaction wasup to61.8%. Then,12target compounds20a、20c、20g、20j~20o and23a~23c wereprepared by3,4-Dihydro-2H-benzo[1,4]oxazine1with haloalkanes.(3)9N-(substituted benzyl)-3,4-dihydro-2H-benzo[1,4]oxazines20a~20i wereprepared by2-(substituted benzylamino)phenols22and1,2-dibromoethane. A comparationof the total yields by Method one and by Method two of the target compounds20a,20c,20g were made, and the results showed that Method one was not suitable for the synthesisof the products with electron donating group on the phenyl ring.(4) N-(2-Bromoethyl)-3,4-dihydro-2H-benzo[1,4]oxazine24was synthesized by3,4-Dihydro-2H-benzo[1,4]oxazine1and1,2-dibromoethane. Then,11novelN-(2-(substitued-aniline)ethyl)-3,4-dihydro-2H-benzo[1,4]oxazines21a~21k wereprepared by N-(2-Bromo-ethyl)-3,4-dihydro-2H-benzo[1,4]oxazine24and substituted anilines.(5) The biological activity of26novel N-substituted-3,4-dihydro-2H-benzo[1,4]oxazines were assayed, and the results showed the fungicidal activity againstSclerotonia sclerotiorum was the best as shown by compounds21h(97.2%activity atconcentration of25mg/L),21g(89.7%). The fungicidal activity against Blumeria graminiswas second as shown by compound20e and20o (90.0%activity at concentration of25mg/L), and80.0%、70.0%for20m and30f, respectively. The compounds againstPhytophythora capsici and Botrytis cinerea had certain fungicidal activity, the activity of20n against Phytophythora capsici was74.8%, the activity of20g and20n against Botrytiscinerea were73.0%. But all the target compounds had no activity against Rhizoctoniasolani. It was further investigated the effects of concentration on bactericidal activity. Theactivity of compounds21g and21h against Sclerotonia sclerotiorum decreased graguallywith the reduction of the concentration of the testing compounds, the fungicidal activity of21g was56.1%at the concentration10mg/L, while0%for21h.