NH-1,2,3-三唑合成之研究

Study on The Synthesis of NH-1,2,3-Triazoles

吳家浩(Jia-Hao Wu)

指導教授 ： 楊嘉喜

中原大學/理學院/化學系/碩士(2006年)

https://doi.org/10.6840/cycu200600253

摘要

1,2,3-三唑的應用非常廣泛包括農業、工業和醫藥等用途。在文獻中有許多氮上接取代基三唑的合成方法，然而對於合成NH-1,2,3-三唑的研究卻非常的少。本實驗探討利用末端炔化合物、疊氮化鈉在氯化亞銅的活化下進行環化加成反應製備高產率NH-1,2,3-三唑。(i)疊氮亞銅與苯乙炔在甲醇溶劑中70℃迴流反應3天：4-苯基-1H-1,2,3-三唑(2a)產率小於10%，苯乙炔二聚體(3a)為主產物；(ii)苯乙炔亞銅與疊氮化鈉在甲醇溶劑中70℃迴流反應3天：(2a)產率33%，(3a)產率34%；(iii)苯乙炔、疊氮化鈉和氯化亞銅在甲醇：1,4-二氧陸圜＝1：2共溶劑中100℃迴流反應2天：(2a)產率81%。改變不同取代基-芳香基、烷基、氫氧基、酯類、環烷和共軛烯炔等進行一系列反應，並將實驗所得產率與文獻之產率比較皆相近或優於文獻報導的產率，且本反應具有位置選擇性只會得到4-取代產物。實驗必須在氮氣下進行反應否則會進行氧化耦合反應產生二聚體。反應溫度需高於顏色轉變溫度約80℃才易進行反應。改變氯化亞銅添加量的實驗中發現當添加1當量時(2a)產率為最高值81%可知Cu(I)並非扮演觸媒的角色。在實驗中並合成出4-苯基-1,3-二氫-1,2,3-三唑陽離子以X-ray鑑定其結構。

關鍵字

亞銅 ； 炔 ； 三唑 ； 疊氮化鈉

並列摘要

1,2,3-triazole have found broad uses in agrochemicals, industrial applications and drugs. Many methods of preapring N-substituted 1,2,3- triazole are reported, whereas, only a few synthesis of N-unsubstituted 1,2,3-triazole were developed. In this study, we report a high yield synthesis of N-unsubstituted triazole by cycloaddition reaction of terminal acetylene and sodium azide activated by copper(I) ion.
(i). The mixture of copper(I) phenyl acetylide and sodium azide dissolved in methanol was stirred at reflux temperature of 70℃ for 3 days : the yield of 4-phenyl-1H-1,2,3-triazole (2a) is less than 10% and phenyl acetylene dimer (3a) is the major product.
(ii). The mixture of copper(I) azide and phenyl acetylene dissolved in methanol was stirred at reflux temperature of 70℃ for 3 days : the yield of (2a) is 33% and the yield of (3a) is 34%.
(iii). The mixture of phenyl acetylene, sodium azide and copper(I) chloride dissolved in a co-solvent (methanol : 1,4-dioxane= 1 : 2) was stirred at reflux temperature of 100℃ for 2 days under nitrogen : the yield of (2a) is 81%.
The same procedure was applied to terminal alkynes carrying substituents such as aryl, alkyl, hydroxyl, ester, cycloalkyl and conjugated enyne to obtain triazoles having corresponding substitutents. The yields of these products are comparable or better then those reported in literature. This reaction isregiospecific and only 4-substituted 1H-1,2,3-triazoles were obtained. The reaction must carry out under inert gases, otherwise oxidative coupling reaction is the dominated reaction, and phenyl acetylene dimmer is the major product. Reaction temperature has to be high enough (>80℃) to allow the color change of the mixture to ensure a high yield reaction. When the rate of copper(I) chloride to phenyl acetylene is 1:1, as the reactant, the optimal yield of 81% is attained. Therefore, copper(I) chloride is not a catalyst.
We also synthesize 4-phenyl-1,3-diH-1,2,3-triazolium cation and its structure determined by X-ray diffraction is described.

並列關鍵字

sodium azide ； alkynes ； triazoles ； copper(I)

參考文獻

(27) Alvarez, R.; Velazquez, S.; San-Felix, A.; Aquaro, S.; De, C. E.; Perno, C. F.; Karlsson, A.; Balzarini, J.; Camarasa, M. J. J. Med. Chem. 1994, 37, 4185-4194.

(1) Wamhoff, H. In Comparehensive Heterocyclic Chemistry; Pergamon: Oxord, 1984; Vol. 5, pp 669-732.

(3) H. von Pechmann Chem. Ber. 1888, 21, 2751.

(8) Kolb, H. C.; Sharpless, K. B. Drug Discov. Today 2003, 8, 1128-1137.

(18) Manecke, G.; Ruehl, C. S. Makromol. Chem. 1979, 180, 103-115.