Fischer indole synthesis, scope

The Fischer indole synthesis is of wide scope, and can be used for the preparation of substituted indoles and related systems. For example reaction of the phenylhydrazone 9, derived from cyclohexanone, yields the tetrahydrocar-bazole 10 ... 

The Fischer indole synthesis is the conversion of an Af-arylhydrazone to an indole with elimination of ammonia (equation 88). This method is of very broad scope, and is able to accomodate a wide variety of functionalized and unfunctionalized 2- and 3-side chains as well as substituents in the carbocyclic ring (B-70MI30605,72HQ25-D232). Ironically, the parent 2,3-unsubstituted indoles are difficult to obtain via the Fischer method. Indole itself was not successfully made by the Fischer method until 1976, and then only using a high temperature (290-300 °C) procedure (76JOC1877). 

This reaction was first reported by Drechsel in 1888 and then by Borsche in 1904. It is the reaction involving the cyclization of arylhydrazones of cyclohexanone to tetrahy-drocarbazoles and the subsequent oxidation of tetrahydrocarbazoles into carbazoles. In this reaction, cyclohexanone phenylhydrazone is converted into tetrahydrocarbazole when heated with dilute sulfuric acid, a process that is completely analogous to the Fischer Indole Synthesis. However, Borsche was the first to realize the full scope of this reaction, and had prepared many substituted tetrahydrocarbazoles. Other acids can also be used in this reaction—for example, acetic acid has been found to give cleaner products. Different oxidants have been applied for converting the tetrahydrocarbazoles into carbazoles, such as lead oxide, mercury acetate, palladium chloride, and chloranil. However, only chlo-ranil was found to be a good reagent in this reaction. In addition, a mixture of cinnamic acid and palladium black is another excellent reagent for the preparation of carbazoles, in which cinnamic acid was reduced to hydrocinnamic acid. 

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