Synthesis And Fungicidal Activity Of 3,1-Benzoxazinopyrazinones And 3,1-Benzoxazinodiazepines

Pesticides play an important role in ensuring agricultural harvest and promoting high-yield and high-efficiency agriculture.Therefore,the development of new pesticides with novel structure,high efficiency,good selectivity,high safety and good environmental compatibility has become one of the hotspots of pesticide researches in recent years.In this paper,a series of novel 11-aryl-3,1-benzoxazinopyrazinones V,9-aryl-3,1-benzoxazinodiazepines VI and VII were designed and synthesized.The structures of the target compounds were characterized by ¹H NMR?¹³C NMR?IR.Single crystals of part of the target compounds were cultured,and the structures of the single crystals were determined by X-ray diffraction.The fungicidal activities of the target compound were investigated.?1?A series of 2-bromoacetamides I-1^I-22 were synthesized in yields of80.2%⁹6.4%by reaction of aromatic amines benzylamine or fatty amine with bromoacetyl bromide in the presence of triethylamine.?2?Reactions of bromoacetamides I and o-aminobenzyl alcohol under the action of K₂CO₃?material ratio:1.0:1.2:1.4?in solvent of V?DMF?:V?THF?=1:2 at 65°C for12 h gave a series of N-arylmethyl-2-?2-hydroxymethylphenyl?acetamides II-1^II-22in yields of 55.4%⁸1.4%.?3?N-Arylmethyl?or aryl?-2-?2-hydroxymethylphenyl?acetamides II were reduced by LiAlH₄ affording 2-?N-substituted aminoethylamino?benzyl alcohol III-1^III-22 in yields of 55.2%⁹2.2%.?4?Reactions of 2-?N-substituted benzylaminoethylamino?benzyl alcohols III with ethyl glyoxylate or ethyl pyruvate gave a series of novel11-?arylmethyl?-3,1-benzoxazinopyrazinones V-1^V-20.The optmized reaction conditions are as follows:the ratio of the compounds III to the ethyl glyoxylate?or ethyl pyruvate?is 1:1.2,La?CF₃SO₃?₃?10%mol?as catalyst,toluene as a solvent,at95°C for 4 h,and the yields were 34.9%⁷1.1%.The reaction yield is related to the substituent R at the 2-position of the benzoxazine ring:the yield of R being a methyl group is significantly lower than those of R being H.?5?Reactions of 2-?N-aromaticaminoethylamino?benzyl alcohols III with ethyl glyoxylate?or ethyl pyruvate?produced two isomers of 3,1-benzoxazinodiazepines VI and VII with cis-VI as main product at high temperature,and with trans-VII as main product at low temperature.However,no 3,1-benzoxazinopyrazinones V is formed at both cases.Under the optimized reaction conditions:the ratio of compound III to ethyl glyoxylate?or ethyl pyruvate?being 1:2.0,La?CF₃SO₃?₃?10%mol?as catalyst,toluene as solvent,a series of cis-9-aryl-3,1-benzoxazinodiazepines VI-1^VI-10 were synthesized in 37.2%⁵0.7%yields at 105°C for 4h.A series of trans-9-aryl-3,1-benzoxazinodiazepines VII-1^VII-8 were synthesized in 22.7%⁶8.5%yields at 35°C for 4h,and 3,1-benzoxazines IV were also produced.For compounds VI and VII,the yields of the benzene ring with electron donating groups are greater than those with electron withdrawing groups.The above experimental results also showed that the reaction products of the reactions of 2-?N-substituted aminoethylamino?benzyl alcohols III and ethyl glyoxylate were closely related to the substituent group linked with the nitrogen atom with good chemical selectivity.When the substituent is an arylmethyl group,the reaction produced only 3,1-benzoxazinopyrazinone V;while the substituent is aryl the reaction produced 3,1-benzoxazinodiazonium VI and VII.?6?The fungicidal activities of the synthesized compounds IV?V?VI and VII were tested.In general,the activities of compounds V?VI?VII are higher than those of compound IV.For compound IV,the fungicidal activities of R¹ being aryl group are higher than those of R¹ being substituted benzyl group.For compound V,the activities of R being methyl are significantly higher than those of R being H.The activities of trans-VII for S.sclerotiorum,B.cinerea and G.zeae are generally higher than those of cis-VI.Secondly,the activities of compounds V-17?V-20 and VI-9 against S.sclerotiorum were 97.7%,and 98.0%activity for compound VII-6,which were all higher than that of the control drug chlorothalonil.The activities of compound VI-10against Magnaporthe oryzae was 86.6%,and the activities of IV-7?VII-3 and VII-4also reached 73.0%,which were all higher than that of chlorothalonil.The activities of compounds V-11?V-17 and VII-4 against Gibberella zeae were 78.8%?82.2%and75.6%,respectively,which were all higher than that of chlorothalonil.The activity of compound VI-10 against Pellicularia sasakii was 86.6%,and the activities of compounds V-7?V-17 and VII-4 were also above 71.0%.