FORMYLATION OF AMINES
FORMYLATION OF AMINES
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DOI：
10.1021/jo01099a023
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发表时间：
1958-01-01
影响因子：
3.6
通讯作者：
HUFFMAN, CW
中科院分区：
文献类型：
--
作者：
HUFFMAN, CW
已有许多方法用于甲酰化胺，但适用范围似乎有限。生物测试需要甲酰亚胺类化合物，因此需要一个通用的甲酰化程序。这项研究的结果表明，乙酸甲酸酐是一种很好的制备胺甲酰化试剂的通用试剂。简要总结各种甲酰化反应过程(特别是本研究中应用于杂环胺的甲酰化反应)的缺点将是有意义的。甲酰胺2用于甲酰化一些苯胺类化合物和胺，如苯甲胺。它没有给出2-氨基-5-硝基噻唑的甲酰基衍生物。甲酸的酯3与一些胺有很好的效果，但通常需要密封管或高压灭菌器。氯45与许多胺反应生成甲酰胺化合物和氯仿。同样，该试剂不与2-氨基-5-硝基噻唑反应。有时，三氯乙醛会产生附加产品。例如，6，2-氨基吡啶与三氯乙醛形成加成化合物C7H7CI3X2O，在真空(11 Mm)下升华。并在106.5度熔化。2-氨基喹恶啉与三氯乙醛反应生成一种奇怪的络合物。这个建筑群在176岁时分解了。它可以由苯结晶，但尝试从异丙醇结晶得到起始的2-氨基喹恶啉(MP 154)。因此，三氯乙醛不能甲酰化某些胺。甲酸单独甲酰化不同的苯胺衍生物，如3，4-二氯苯胺。6即使是弱碱性的苯胺，如3，5-二硝基苯胺7，与大量的甲酸(8摩尔)回流时，甲酰衍生物的产率也适中(50%)。在某些情况下，乙酸酐被加入甲酸过量的胺溶液中。用该方法合成了2-(5-硝基噻唑基)甲酰胺。8
Many procedures have been used to formylate amines, but the range of applicability appears to be limited. Formamido compounds were required for biological testing, so that a general formylation procedure was desired. The results of this research show that acetic formic anhydride is an excellent general reagent for the preparation of formyl de-rivatives of amines.A brief summary of the shortcomings of various formylation procedures (particularly as applied to heterocyclic amines in this study) will be of interest. Formamide2 serves to formylate some aniline de-rivatives and amines such as benzylamine. It did not give the formyl derivative of 2-amino-5-nitrothiazole. Esters3 of formic acid gave good results with a number of amines, but sealed tubes or autoclaves are often required. Chloral4 5reacts with many amines to furnish the formamido compound and chloroform. Again, this reagent did not react with 2-amino-5-nitrothiazole. Sometimes chloral gives addition products. For example, 6 2-amino-pyridine and chloral formed the addition compound C7H7CI3X2O which sublimed under vacuum(11 mm.) and melted at 106.5. An odd complex re-sulted from a reaction between 2-aminoquinoxaline and chloral. This complex decomposed at 176. It could be crystallized from benzene, but an attempted crystallization from 2-propanol gave the starting 2-aminoquinoxaline (mp 154). Therefore chloral fails to formylate some amines. Formic acid alone formylates varied aniline derivatives such as 3, 4-dichloroaniline. 6 Even weakly basic anilines such as 3, 5-dinitroaniline7 gave moderate (50%) yields of the formyl derivative upon reflux with a large excess(8 moles) of formic acid. In some cases, acetic anhydride has been added to a solution of amine in an excess of formic acid. Such a procedure was used to prepare 2-(5-nitrothiazolyl) formamide. 8