A DETAILED, CONVENIENT PREPARATION OF DIMETHYL "1,2,4,5-TETRAZINE-3,6-DICARBOXYLATE
A DETAILED, CONVENIENT PREPARATION OF DIMETHYL "1,2,4,5-TETRAZINE-3,6-DICARBOXYLATE
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DOI：
10.1021/jo00225a076
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发表时间：
1985-12-13
影响因子：
3.6
通讯作者：
SAUER, J
中科院分区：
文献类型：
--
作者：
BOGER, DL;COLEMAN, RS;SAUER, J
4 R= CH3 co2ch3证明了其制备过程。我们偶尔会遇到困难，难以从先前发表的工作中提供的信息中方便地复制1的准备工作，并且迄今为止没有报告详细说明1的准备工作的完整程序。在此，我们详细介绍了一种方便、大规模、四步制备1的方法，该方法能够提供20-40 g材料（总收率为34%），该方法基于Curtis报道的原始碱促进重氮乙酸乙酯二聚化反应48，Wiberg最初详细介绍的改进的质子化反应过程4b， Sauer开发的改进和方便的e- terification过程，4c和利用氮气的新的改进的氧化过程（方案1）。通过直接将2转化为4来缩短这一过程的尝试没有成功，利用其他酯化方法将3转化为4的尝试也不太成功，将1,2,4,5 -四氮- 3,6 -二羧酸酯酯化的尝试也不成功，将4转化为18的替代氧化方法也不太成功。这些尝试的失败和我们描述的两个步骤的适度产率可以归因于系统的反应性。二甲基1,2,4,5 -四嗪- 3,6 -二羧酸酯(1)在硅胶上不完全稳定，在升温时分解缓慢，并且像二氢- 1,2,4,5 -四嗪3/4一样容易发生酸促进重排。(4)(a) Curtius, t；Darapsky, a;m . ller， E. Ber. 1906, 39,3410；1907, 40,84；1908, 41, 3161。库尔修斯、t;Lang, JJ Prakt。化学，1888,38,531。汉栖,a;李建平，刘建平。2009,33 - 36。汉栖,a;西尔伯拉德，O. Ber. 1900, 33, 58。(b)斯宾塞，g.h.；Jr .);克罗斯，p.c.；韦伯格，k.b.j.化学。物理学：1961、35、1939。(c)绍尔，J.；Mielert, a;朗,d;Peter，化学博士。1965年，1998年，1435年。(5)例如，用亚硫酰氯在甲醇中在0℃（0.5 h）和25℃（6 h）下处理2不能提供4。(6)例如，在乙醚中用重氮甲烷处理3，除了jv甲基化的物质外，只有4的产率很低；参见：Lin， c.h.；利,大肠;霍维茨，JP J. Am。化学。社会科学。1954,76,427。简单的Fischer酯化法（甲醇/盐酸）不能产生4。(7)例如，1,2,4,5 -四嗪- 3,6 -二羧酸用乙醚中的重氮甲烷或甲醇/二环己基碳酰亚胺/1-羟基苯并三唑在二甲基甲酰胺中处理均不能提供1。1,2, 4,5 -四嗪- 3,6 -二羧酸二钠与二甲基甲酰胺或六甲基磷酰胺中的碘化物或甲醇中的亚硫酰氯处理均不能提供1。(8)我们探索的将4转化为1的方法不成功（二氯甲烷中的Mn02）或不如本文详细介绍的方法（KN02，醋酸/苯）成功。
4 R= CH3 co2ch3 proved procedure for its preparation. We have had oc-casional difficulty conveniently reproducing the prepara-tion of 1 from the information that is available in prior published work, and to date no report details a complete procedure for the preparation of 1. Herein, we detail a convenient, large scale, four-step preparation of 1 that is capable of providing 20-40 g of material (34% overallyield) and is based on the original base-promoted dimerization of ethyl diazoacetate reported by Curtis, 48 an improved protonation procedure detailed originally by Wiberg, 4b an improved and convenient es-terification developed by Sauer, 4c and a new, modified oxidation procedure utilizing nitrous gases (Scheme I). Attempts to shorten this procedure by direct conversion of 2 to 4 have not been successful, 4 5 attempts to convert 3 to 4 utilizing other methods of esterification have been less successful, 6 efforts to esterify l, 2, 4, 5-tetrazine-3, 6-dicarboxylate7 have not been successful, and alternative oxidation methods for the conversion of 4 to l8 were less successful. The failure of these attempts and the modest yields in two of the steps we describe can be attributed to the reactivity of the system. Dimethyl 1, 2, 4, 5-tetrazine-3, 6-dicarboxylate (1) is not completely stableto chroma-tography on silica gel, undergoes slowdecomposition upon warming, and like dihydro-1, 2, 4, 5-tetrazines 3/4 is prone to acid-promoted rearrangement.(4)(a) Curtius, T.; Darapsky, A.; Müller, E. Ber. 1906, 39, 3410; 1907, 40, 84; 1908, 41, 3161. Curtius, T.; Lang, JJ Prakt. Chem. 1888, 38, 531. Hantzsch, A.; Lehmann, M. Ber. 1900, 33 3668. Hantzsch, A.; Silberrad, O. Ber. 1900, 33, 58.(b) Spencer, G. H.; Jr.; Cross, P. C.; Wiberg, K. B. J. Chem. Phys. 1961, 35, 1939.(c) Sauer, J.; Mielert, A.; Lang, D.; Peter, D. Chem. Ber. 1965, 98, 1435.(5) For instance, treatment of 2 with thionyl chloride in methanol at 0 C (0.5 h) and 25 C (6 h) failed to provide 4.(6) For instance, treatment of 3 with diazomethane in ether provided only poor yields of 4 in addition to JV-methylated material; see also: Lin, C. H.; Lieber, E.; Horwitz, JP J. Am. Chem. Soc. 1954, 76, 427. Simple Fischer esterification (methanol/hydrochloric acid) failed to produce 4.(7) For instance, treatment of l, 2, 4, 5-tetrazine-3, 6-dicarboxylic acid with diazomethane in ether or with methanol/dicyclohexylcarbodi-imide/1-hydroxybenzotriazole in dimethylformamide failed to provide 1. Treatment of disodium l, 2, 4, 5-tetrazine-3, 6-dicarboxylate with methyl iodide in dimethylformamide or hexamethylphosphoramide or with thionyl chloride in methanol failedto provide 1.(8) Our methods exploredin an effort to convert 4 to 1 were unsuc-cessful (Mn02 in methylene chloride) or less successful than the proce-dure detailed herein (KN02, acetic acid/benzene).