杏耀测速地址

      由邻取代硝基苯和乙烯基制备7-取代吲哚的反应。该方法常用于制备7位取代的吲哚类衍生物。类似的反应还有 Leimgruber-Batcho吲哚合成，但 Bartoli 吲哚合成的优点在于这个反应可以在碳环和杂环上都引入取代基。

底物硝基邻位无取代基时，反应一般不能发生。通常用三倍量的格氏试剂，确保产率。

综述：Bartoli, G.; Dalpozzo, R.Nardi, M. Chem. Soc. Rev. 2014, 43, 4728.

在这反应被开发之前，其实有很多用于合成吲哚骨架的类似反应，在这些反应中，确唯独没有一种能够合成7位取代吲哚的反应。1989年意大利的化学家Bartoli等人开发出了该反应，因此该方法被称为Bartoli Indole合成法，是制备 7-取代吲哚的较好方法。

反应机理

至少需要两个当量的格氏试剂

反应实例

 Bartoli, G.; Palmieri, G.; Bosco, M.; Dalpozzo, R. Tetrahedron Lett. 1989, 30,

2129-2132.

 Dobbs, A. J. Org. Chem. 2001, 66, 638-641

Huleatt, P. B.; Choo, S. S.; Chua, S.; Chai, C. L. L. Tetrahedron Lett. 2008, 49, 5309-5311.

Buszek, K. R.; Brown, N.; Luo, D. Org. Lett. 2009, 11, 201-204.

Grant, S. W.; Gallagher, T. F.; Bobko, M. A.; Duquenne, C.; Axten, J. M. Tetrahedron Lett. 2011, 52, 3376-3378.

The 2-nitrotoluene (685 mg, 5mmol) was placed in a two–necked round bottomed flask fitted with a gas inlet(argon) and rubber septum. The flask was purged several times with argon beforeadding THF (35–40 ml) and cooling to between –40 and –45 °C. The Grignard reagent (3 eq.) was then addedrapidly in one portion to the THF solution and stirring continued for a further30 mins to 1 hour (exact length of time had little effect on yield). Saturatedammonium chloride solution was added to the reaction mixture (at ca. –40 °C) before allowing the mixture towarm to room temperature. The mixture was thoroughly extracted with diethylether (2 x 200 ml), the ether extracts combined and thoroughly washed withfurther ammonium chloride (300 ml), water (300 ml) and brine (300 ml) beforedrying (MgSO4) and concentrating in vacuo to give a dark brown gum, which was purifiedby flash column chromatography (hexane:ethyl acetate 9:1) to give 465 mg of7-methyl-indole. Yield: 71%.

 

Ref: (a) Adrian P. Dobbs,Martyn Voyle, Neil Whittall, Synlett, 1999, 1594, (b) Curtin, M.L et al, J.Med.Chem.,1998, 74.

Dobbs改良法： Adrian Dobbs 用邻位的溴作定位基成环，反应后再用偶氮二异丁腈和三丁基锡烷将溴除去，生成 7-位无取代基的吲哚(参考维基百科)。

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