【作者】 陈卫文；

【导师】 刘汉文； 唐子龙；

【作者基本信息】 湖南科技大学 ， 有机化学， 2009， 硕士

【摘要】 杂环化合物是有机化合物中最庞大的一类,约占65%以上,而且在自然界分布也十分广泛。杂环化合物的结构干变万化,具有特殊的性质和重要用途,其中3,4-二氢-2H-1,3-苯并噁嗪就是一类非常重要的杂环化合物,具有广泛的杀菌,抗肿瘤和抗癌等生物活性。本文主要研究了2,3-二取代-3,4-二氢-2H-1,3-苯并噁嗪化合物的合成方法,找到了一条有效的合成途径,并合成了16个新的2,3-二取代-3,4-二氢-2H-1,3-苯并噁嗪化合物和4个3-取代-3,4-二氢-2H-1,3-苯并噁嗪化合物,对所合成的二氢苯并噁嗪31a-31t的结构用IR,1HNMR和13C NMR进行了表征,部分化合物的结构用质谱进行了表征。初步研究了所合成化合物的杀虫和杀菌活性。以水杨醛和取代苯胺为原料,高产率地合成了水杨醛缩取代苯胺席夫碱29a-29f,然后用硼氢化钠还原得到2-((取代苯基氨基)甲基)苯酚,最后2-((取代苯基氨基)甲基)苯酚与芳醛在催化剂的作用下反应得到2,3-二取代-3,4-二氢-2H-1,3-苯并噁嗪和3-取代-3,4-二氢-2H-1,3-苯并噁嗪。考察了不同催化剂对反应的影响,结果表明SnCl4的催化效果优于对甲苯磺酸和硫酸。提出了二氢苯并噁嗪31生成的可能反应机理,根据反应机理解释了SnCl4的催化效果比对甲苯磺酸和硫酸的效果好的原因。重点考察了在SnCl4催化作用下,反应物物质的量的比、SnCl4的用量、反应温度和环己烷／三氯甲烷溶剂配比对反应产率的影响,得到了较优反应条件：反应物物质的量的比为1.3:1, SnCl4的用量为20 mol%,反应溶剂为三氯甲烷／环己烷(V／V=1：7)的混合溶剂,反应温度为85℃,在此条件下反应产率高达94.7%。并且发现与氮原子相连的苯环对位上的取代基为甲基和甲氧基时的化合物(31b、31c、31o、31q)的产率均高于取代基为氯时的化合物(31l、31m)的产率。对所合成的16种新的2,3-二取代-3,4-二氢-2H-1,3-苯并噁嗪和4种3-取代-3,4-二氢-2H-1,3-苯并噁嗪进行了生物活性测试。结果表明,二氢苯并噁嗪具有较好的杀虫(蚜虫、粘虫和棉红蜘蛛)和优良的杀菌活性(6种菌),杀菌活性高于杀虫活性。对于杀虫活性来说,杀蚜虫的活性最高,化合物31s的杀蚜虫活性高达80.00%(剂量：500mg/L),并在大多数情况下,2-位有取代基的二氢苯并噁嗪的杀蚜虫活性大于2-位无取代基的二氢苯并噁嗪的活性。对于杀菌活性来说,目标化合物对稻纹枯病菌的活性最高,其中化合物31b对稻纹枯病菌的防效率高达100%(剂量：500mg/L),31e、31h、31o和31r防效率均达80%；其次是对油菜菌核病菌的活性,化合物31n对该菌的抑制率为78.5%(剂量：25mg／L),化合物311的活性为74.8%。与杀蚜虫活性类似,在大多数情况下2-位有取代基的二氢苯并噁嗪对稻纹枯病菌的防效活性比2-位无取代基的二氢苯并噁嗪的活性高。更多还原

【Abstract】 Heterocyclic compounds that account for about 65% organic compounds occur in a wide range of natural distribution. Heterocyclic compounds vary in structures and nature, and always find important uses.3,4-dihydro-2H-1,3-benzoxazine is a very important kind of heterocyclic compound and always exhibits a broad biological activity, such as bactericidal, anti-tumor and anti-cancer activity. This paper mainly studied the synthesis method of 2,3-disubstituted-3,4-dihydro-2H-1,3-benzoxazines and an efficient synthesis route was found. By this route,16 novel 2,3-disubstituted-3,4-dihydro-2H-1,3-benzoxazines and 4 3-disubstituted-3,4-dihydro-2H-1,3-benzoxazines were prepared, and their structures were characterized by IR,1HNMR, 13CNMR and part of the compounds characterized by MS. It was also investigated their insecticidal and fungicidal activity.The first imtermediate Schiff Bases 29a-29f were synthesized in good yields by reaction of salicylaldehyde with substituted aniline. Then, reduction of these Schiff Bases by sodium borohydride in methanol afforded 2-((substituted-phenyl-amino)-methyl)-phenol 30a-30f. The target compound 3,4-dihydro-2H-1,3-benzoxazines (31a-31t) were prepared by reactions of 2-((amino-substituted phenyl)methyl) phenols with substituted benzaldehydes in the presence of catalyst. It was studied the effects of catalysts on the reaction, and the results showed that SnCl4 was better than p-toluenesulfonic acid (TsOH) and sulfuric acid. A plausibal mechanism of the formation of 31a-31t was proposed, and by which the better effect of SnCl4 than TsOH and sulfuric acid was explained.The studies focued on the catalysis reaction conditions by SnCl4. It was investigated the effects of the molar ratio of reactants (m-nitrobenzaldehyde and 2-((amino-p-tolyl)methyl)phenol), the amount of SnCl4, reaction temperature and solvent (the value ratio of cyclohexane and chloroform) on the yields, and an optimized condition was obtained:the molar ratio of reactants being 1:3, the amount of SnCl4 being 20 mol%, the value ratio of cyclohexane and chloroform being 1:7, reaction temperature being 85℃. Under this optimized condition, the yields of the reactions were up to 94.7%. And moreover, the yields of the compounds with the substituents on the phenyl group connected with the nitrogen atom being methyl and methoxy group (31b、31c、31o、31q) were higher than those of compounds with chloride (31l、31m).It was tested the biological activity of 16 novel 2,3-disubstituted-3,4-dihydro-2H-1,3-benzoxazines and 3-disubstituted-3,4-dihydro-2H-1,3-benzoxazines. The results showed that the dihydrobenzoxazines exhibited relative good insecticidal activity and exellent fungicidal activity. In the case of insecticidal activity, the tested compounds exhibited the higest activity against Aphis fabae as shown by the activity of compound 31s being 80%at dosage of 500mg/L. In most cases, the activity of 2,3-disubstituted 3,4-dihydrobenzoxazines were higher than 3-substituted 3,4-dihydrobenzoxazines. For fungicidal activity, the tested compounds exhibited the higest activity against Rhizoctonia solani. The activity of compound 31b was up to 100%at dosage of 500mg/L, and the coresponding activity of 31e、31h、31o、31r was up to 80%. The tested compounds exhibited the second higest activity against Sclerotonia sclerotiorum, and the activity of 31n、311 was up to 78.5%at dosage of 25mg/L and 74.8%, respectively. In most cases of the fungicidal activity against Rhizoctonia solani,2,3-disubstituted 3,4-dihydrobenzoxazines showed higher activity than 3-substituted 3,4-dihydrobenzoxazines.更多还原