Song Jiho, Kang Hae Ju, Lee Jung Wuk, Wenas Michelle A, Jeong Seung Hwarn, Lee Taeho, Oh Kyungsoo, Min Kyung Hoon
College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
College of Pharmacy, Kyungpook National University, Daegu, Republic of Korea.
PLoS One. 2017 Aug 23;12(8):e0183575. doi: 10.1371/journal.pone.0183575. eCollection 2017.
In view of the few reports concerning aromatic nucleophilic substitution reactions featuring an alkoxy group as a leaving group, the aromatic nucleophilic substitution of 2,4-dimethoxynitrobenzene was investigated with a bulky t-butoxide nucleophile under microwave irradiation. The transetherification of 2,4-dimethoxynitrobenezene with sodium t-butoxide under specific conditions, namely for 20 min at 110°C in 10% dimethoxyethane in toluene, afforded the desired product in 87% yield with exclusive ortho-selectivity. A variety of reaction conditions were screened to obtain the maximum yield. The aromatic nucleophilic substitution of 2,4-dimethoxynitrobenzene with t-butoxide should be carried out under controlled conditions in order to avoid the formation of byproducts, unlike that of dihalogenated activated benzenes. Among the formed byproducts, a major compound was elucidated as 2,4-dimethoxy-N-(5-methoxy-2-nitrophenyl)aniline by X-ray crystallography.
鉴于关于以烷氧基作为离去基团的芳香亲核取代反应的报道较少，在微波辐射下，用体积较大的叔丁氧基亲核试剂研究了2,4-二甲氧基硝基苯的芳香亲核取代反应。在特定条件下，即2,4-二甲氧基硝基苯与叔丁醇钠在110℃于甲苯中10%的二甲氧基乙烷中反应20分钟，发生的转醚化反应以87%的产率得到了所需产物，且具有唯一的邻位选择性。筛选了各种反应条件以获得最大产率。与二卤代活化苯不同，2,4-二甲氧基硝基苯与叔丁氧基的芳香亲核取代反应应在可控条件下进行，以避免副产物的形成。在生成的副产物中，通过X射线晶体学确定一种主要化合物为2,4-二甲氧基-N-(5-甲氧基-2-硝基苯基)苯胺。
