【作者】 何旺；

【导师】 白红进； 谢卫青；

【作者基本信息】 塔里木大学 ， 生物资源化学， 2021， 硕士

【摘要】 含有脲结构的化合物一直是一类非常重要的有机化学及化工用品,目前已知的关于脲类化合物的合成方法,其中包括传统的合成方法和近些年发现的新型合成方法都存在一定的不足之处。本文旨在开发一种无金属,溶剂促进,高效,便捷和一锅法的方法,用于由易于制备和处理的二噁唑酮和胺来构建各种脲。本文的方法是一种温和绿色的一锅合成脲类衍生物的方法,该方法可能在药物合成中具有潜在的应用价值。本文以二噁唑酮类化合物为反应底物,加入当量的一级或二级胺,以三氟乙醇（TFE）作为反应溶剂,在常压、50℃、不加入催化剂和添加剂的条件下,实现了一锅法制备脲类化合物及其衍生物。该反应与高压反应相比减少了对反应设备的要求以及反应过程中可能出现危险的概率;与贵金属催化的反应相比,无金属及添加剂降低了反应的成本、后处理更加简单,产物易于分离纯化,同时也与绿色化学发展方向保持一致;同时,该反应实现了脲类化合物及其衍生物的克级制备,有望用于含有脲类结构的农药产品的工业生产之中。以苯基二噁唑酮为模板底物,和N-甲基苯胺反应合成1-甲基-1,3-二苯基脲。筛选了反应时间、反应温度、反应溶剂、反应催化剂、胺的用量对本实验的影响,通过对照试验来优化反应条件,最终确定了最佳的反应条件:苯基二噁唑酮1当量（0.1 mmol）,N-甲基苯胺1.1当量（0.11 mmol）,反应时间为18h,反应温度为50℃,反应溶剂为TFE（1m L）,在该反应条件下,1-甲基-1,3-二苯基脲的收率可以达到90%。在适当改变反应条件的情况下,将苯基噁唑酮以及N-甲基苯胺更换为不同的噁唑酮和一级、二级胺即可得到相应的脲类化合物。对使用本方法合成的脲类化合物的生物活性进行了测定,测定了其对大肠杆菌和金黄色葡萄球菌等六种常见菌株的抑菌活性,结果表明合成的多个脲类化合物都具有一定的生物活性,其中化合物3bb的活性尤为突出,并测定了化合物3bb的最小抑菌浓度值（MIC）。通过核磁共振氢谱（¹H NMR）、核磁共振碳谱(¹³C NMR)以及高分辨质谱（HMRS）进行化合物结构鉴定。同时对该反应的机理进行了探索,并推测了其可能的反应机理。更多还原

【Abstract】 Compounds containing urea structure are always a very important class of organic chemistry and chemical products.Currently,the synthetic methods of urea compounds include traditional synthetic methods and new synthetic methods which discovered in recent years have some shortcoming.This article intends to develop a metal-free,solvent-promoted,efficient,convenient and one-pot method for the construction of various ureas from dioxazolones and amines that are easy to prepare and easy to handle.This transformation represents a gentle and green one-pot synthesis of urea derivatives,which may have potential applications in drug synthesis.In this paper,dioxazolone compounds are used as reaction substrates,equivalent primary or secondary amines are added,trifluoroethanol（TFE）is used as reaction solvent,normal pressure,reaction temperature is 50℃,and no catalysts and additives are added.Under the conditions,the one-pot method can be used to prepare urea compounds and their derivatives.Compared with the high-pressure reaction,this reaction reduces the requirements for reaction equipment and the probability of danger in the reaction process;compared with the reaction catalyzed by noble metals,the reaction without metals and additives not only reduces the cost of the reaction,but also makes the post-reaction treatment more simple,the product is easy to separate and purify,and it is also consistent with the current development direction of green chemistry.At the same time,the reaction realizes the gram-level preparation of urea compounds and their derivatives,which is expected to be applied to pesticides containing urea structures In industrial production.In this paper,phenyloxazolone was used as a template substrate to react with N-methylaniline to synthesize 1-methyl-1,3-diphenylurea.The effects of reaction time,reaction temperature,reaction solvent,reaction catalyst,and amine dosage on this experiment were screened.The reaction conditions were optimized through control experiments,and the best reaction conditions were finally determined:1equivalent of phenyloxazolone（0.1 mmol）,N-methylaniline 1.1 equivalents（0.11 mmol）,reaction time 18h,reaction temperature 50℃,reaction solvent is TFE（1m L）,under the reaction conditions,1-methyl-1,3-diphenyl The yield of urea can reach the highest 90%.Under the condition of appropriately changing the reaction conditions,the corresponding urea compounds can be obtained by replacing the phenyloxazolone and N-methylaniline with different oxazolones and primary and secondary amines.The biological activity of the urea compounds synthesized by this method was measured,and its antibacterial activity against six common strains such as Escherichia coli and Staphylococcus aureus was determined.The results showed that multiple urea compounds synthesized had certain properties.Biological activity,especially the activity of compound 3bb,and the minimum inhibitory concentration value（MIC value）of compound 3bb was determined.The structure of the compound was identified by hydrogen nuclear magnetic resonance spectroscopy（¹H NMR）,carbon nuclear magnetic resonance spectroscopy(¹³C NMR)and high resolution mass spectrometry（HMRS）.At the same time,the reaction mechanism of the reaction was explored and the possible reaction mechanism was speculated.更多还原