Cyclohexanone Borsche-Drechsel cyclization

Borsche-Drechsel cyclization. Acid-catalyzed rearrangement of cyclohexanone phenylhy-drazone to tetrahydrocarbazole. Subsequent oxidation yields carbazole. 

The Borsche-Drechsel cyclization, also known as Borsche carbazole synthesis, is the two-step conversion of phenyl hydrazine and cyclohexanone derivatives to the corresponding carbazole. The first step, which is analgous to the Fischer Indole synthesis, converts the phenyl hydrazine 1 and cyclohexanone 2 to the tetrahydrocarbazole 3. The second step is the oxidation of the terahydrocarbazole to the corresponding carbazole 4. 

The first step of the Borsche-Drechsel cyclization proceeds through the same mechanism as the Fischer indole synthesis. The aryl hydrazine and cyclohexanone condense to form the iminium 5 and water. The imine nitrogen then coordinates to the Lewis acid, which causes a tautomerization of the hydrazone to the ene—hydrazine 6. This ene-hydrazine undergoes a [3,3]-sigmatropic rearrangement to form the iminium ion 7. Rearomitization through deprotonation of the benzylic proton releases the nucleophilic... 

Initially, sulfuric acid was used to initate the Borsche—Drechsel cyclization. However, Perkin found that acetic acid provided cleaner products. Recently, other reagents—such as cerium ammonium nitrate (CAN) and the more environmentally friendly acidic ionic liquids —have been used to catalyze the ring formation. It should be noted that people have found it difficult to promote the cyclization when there are substituents at the ortho-position of the phenylhydrazine. This difficulty becomes more pronounced when both the hydrazine and the cyclohexanone have a-substitution This difficulty usually leads to low yields compared with other methods of forming the carbazole. 

Borsche—Drechsel Cyclization Reaction of Cyclohexanone with (2,5-Dimethyl-4-Nitrophenyl)Hydrazine to Provide 1,4-Dimethyl-3-Nitro-9H-Carbazole ... 

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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See also in sourсe #XX -- [ ]

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