【作者】 邵志强；

【导师】 林原斌；

【作者基本信息】 湘潭大学 ， 有机化学， 2011， 硕士

【摘要】 胺甲基化反应是众多化学反应中非常重要的一类反应,尤其是曼尼希(Mannich)胺甲基化反应。利用Mannich反应可以合成出许多在医药、涂料、香料、有机助剂、农药等行业有重大应用价值的医药中间体、精细有机化学品及一般方法难以合成的化合物。本文选择廉价的多聚甲醛和乙酰胺或氯乙酰胺作为酰胺甲基化试剂,在酸催化下,采用一锅法,对芳香化合物的酰胺甲基化反应进行了研究,该反应也属于Mannich反应。但一般Mannich反应都是以醛、酮或含活泼氢的芳烃作为酸性组分,二级胺为碱性组分。而本文以芳烃为酸性组分,不仅包括活泼芳烃,还包括钝化芳烃、杂环芳烃,以一级酰胺为碱性组分,这种从二级胺到一级酰胺的变换是一种非常有用的改变,不仅阻止了一级胺的多次胺甲基化,也是一种一步合成酰胺甲基芳环化合物的有效方法。该类酰胺甲基化合物非常稳定、易于保存,在酸性或碱性条件下可水解成伯胺甲基芳环化合物,从而对伯胺甲基芳环化合物起到了保护作用。通过对芳香化合物的酰胺甲基化反应的研究,找到了部分芳环酰胺甲基化反应的最佳条件,同时也确立了一条经芳环酰胺甲基化反应,再水解制备伯胺甲基芳环的路线。该方法操作简单,原料便宜,反应条件温和,后处理简单,产率适中。本文合成了N-(2-甲基-5-硝基苄基)乙酰胺、N-(2,5-二甲基苄基)乙酰胺、2,5-二(乙酰胺甲基)对二甲苯、N-(2,4-二甲基苄基)乙酰胺、4,6-二(乙酰胺甲基)间二甲苯、N-(3,4-二甲基苄基)乙酰胺、N-(2,5-二氟苄基)乙酰胺、N-(4-甲基苄基)乙酰胺、N-(4-氯苄基)乙酰胺、N-(2-氯-5-三氟甲基苄基)乙酰胺、2-氯-5-乙酰胺甲基苯甲酸、4,4′-二氯乙酰胺甲基联苯、4-乙酰胺甲基联苯、α-乙酰胺甲基萘、2-乙酰胺甲基噻吩等。其次,本文还考察了酰胺甲基芳烃的水解,合成了4,4′-二氨甲基联苯盐酸盐、2-甲基-5-硝基苄胺盐酸盐、2,5-二甲基苄胺盐酸盐、2,5-二氟苄胺盐酸盐、2,5-二胺甲基对二甲苯盐酸盐。本文通过1H NMR和13C NMR等手段对所合成的各种目标产物的结构进行了表征,确定了它们的结构,所得结果与文献报道的数值或理论推测一致。其中,N-(2,5-二氟苄基)乙酰胺、N-(2-氯-5-三氟甲基苄基)乙酰胺未见文献报道合成的新化合物。更多还原

【Abstract】 Aminomethylation, especially Mannich aminomethylation, is one of the most important kinds of organic reactions. Mannich reaction can be used to synthesize lots of important compounds such as pharmaceutical intermediates and fine organic chemicals which have been applied in medicine, coatings, spices, organic fertilizer, pesticides, polymer materials and other industries. In addition, some compounds that are difficult to synthesize by general methods can be obtained by Mannich reaction.In this paper, we studied one-pot amidomethylation of aromatic compounds with low-cost polyformaldehyde, acetamide or 2-chloroacetamide as amidomethylation reagent and acid as catalyst. This reaction also belongs to Mannich reaction. Generally, in Mannich reaction aldehydes, ketones or aromatic compounds containing active hydrogens as acid components and secondary amines as alkaline components were utilized. However, in this paper, we chose passivated aromatic compounds and heterocyclic compounds as well as active hydrogens-containing aromatic compounds as acid components and primary amide for alkaline components. Transformation of secondary amine into primary amide is a very significant change that not only prevents consecutive aminomethylation of primary amine but also provides a one-step methord for the direct synthesis of amidomethyl aromatic compounds. These amidomethyl aromatic compounds are very stable and easy to store. Under acidic or alkaline conditions, they can be hydrolyzed into primary aminomethyl aromatic compounds. Thus it is helpful for the preservation of primary aminomethyl aromatic compounds.By investigating of various factors that influence reaction yield, the best conditions of amidomethylation of some aromatic compounds were found. Mea-nwhile, by amidomethylation and hydrolysis, a route of the preparation of pri-mary aminomethyl aromatic compound was established. This method has many advantages such as simple operation, cheap raw materials, mild reaction condition and simple post-processing. Some compounds were synthetized as follows: N-(2-methyl-5-nitrobenzyl)acetamide, N-(2,5-dimethylbenzyl)acetamide, 2,5-diacet- amidomethyl-1,4-dimethylbenzene, N-(2,4-dimethylbenzyl)acetamide, 4,6-diaceta- midomethyl-1,3-dimethylbenzene, N-(3,4-dimethylbenzyl)acetamide, N-(2,5-difluor- obenzyl)acetamide, N-(4-methylbenzyl)acetamide, N-(4-chlorobenzyl)acetamide, N- (2-chloro-5-(trifluoromethyl)benzyl)acetamide, 5-(acetamidomethyl)-2-chlorobenzoic acid, 4,4’-(dichloroacetamidomethyl)biphenyl, 4-acetamidomethylbiphenyl,α- acetamidomethylnaphthalene, 2-acetamidomethylthiophene.In addition, hydrolysis of acetamidomethyl aromatics was studied. 2-Methyl-5-nitrobenzylamine hydrochloride, 4,4’-(diaminomethyl)biphenyl hydro- chloride, 2,5-dimethylbenzylamino hydrochloride, 2,5-difluorobenzylamino hydro- chloride and 2,5-diaminomethyl-1,4-dimethylbenzene hydrochloride were successfully prepared.The structures of all the synthesized compounds were confirmed by 1H NMR, 13C NMR and other means. All characterization results of these compounds are consistent with the reported data or theoretical consequences. Among them, N-(2-chloro-5-(trifluoromethyl)benzyl)acetamide, N-(2,5-difluorobenzyl)acetamide are new compounds that have not been reported in any other literature.更多还原