Fischer-Borsche synthesis

A large rtumber of carbazole syntheses involve the preparation and dehydrogenation of hydrocarbazoles, mainly 1,2,3,4-tetrahydrocarbazoles. They are usually prepared by either the Fischer-Borsche synthesis or the Japp-Klingemann reaction. The most commonly used dehydrogenating agents are palladium on charcoal or chloranil (495,496). 

FISCHER - BORSCHE - DRECHSEL Indole synthesis Indole synlhesis Irom phenylhydrazones ol ketones (Fischer), m the case ol cyclohexanone phenylhydrazones letrahydrocarbazoles are oblained (Borsche-Drechsel). 

Bhattacharyya et al. reported the first total synthesis of clausenalene (90) to establish its structure (99). This total synthesis uses Japp-Klingemann and Fischer-Borsche reactions as key steps. The phenyl hydrazone 1000 required for the transformation to 1-0x0-tetrahydrocarbazole 1001 under Fischer-Borsche conditions was obtained by condensation of 2-hydroxymethylene-5-methylcyclohexanone (999) with diazotized 3,4-methylenedioxyaniline (998) using Japp-Klingemann conditions. Wolff-Kishner reduction of 1001 furnished 3-methyl-6,7-methylenedioxy-l,2,3,4-tetrahydrocarbazole (1002), which, on aromatization wifh 10% Pd/C in decalin, afforded clausenalene (90) (99) (Scheme 5.143). 

The Borsche synthesis of tetrahydrocarbazoles 21 is a special case of the Fischer indole synthesis in which cyclohexanone phenylhydrazones 20 are used as the starting materials (Scheme 9) (see, e.g., <2009BML4110>). 

FISCHER Oxazole synthesis 122 FISCHER - BORSCHE DRECHSEL Indole synthesis 123... 

FISCHER BORSCHE DRECHSEL Indole synthesis Indole synthesis from phenylhydrazones of ketones (Fischer) in the case of cyclohexanone phenylhydrazones tetrahydrocarbazoles are obtained (Borsche-Drechsel). 

Carbazole derivatives (carbazole itself is 320) are also an important structural feature of many alkaloids. The Borsche-Drechel cyclization 90 is a Friedel-Crafts route to these compounds, which is related to the Fischer indole synthesis discussed in Section 12.5.C. This sequence begins with phenylhydrazone derivatives... 

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. 

Also known as Borsche carbazole synthesis, is the two-step conversion of phenyl hydrazine and cyclohexanone derivatives to the corresponding carbazole. Cf. Fischer indole synthesis. 

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... 

Review N. V. Sidgwick, Organic Chemistry of Nitrogen Compounds (Oxford, 3rd ed., 1966) pp 619-641 H. Posvic etal, J. Org. Chem. 39,2575 (1974). Cf. Borsche-Drechsel Cvclization Fischer Indole Synthesis. 

The Fischer method (497) of indole synthesis by the indolization of an arylhydrazone by treatment with an acid catalyst was applied to the synthesis of tetrahydrocarba-zoles by Borsche (498). 

The Fischer cyclization can be applied to carbazoles by using cyclohexanones as the carbonyl component. The resulting product is a tetrahydrocarbazole which can be aromatized by standard techniques for dehydrogenation. In the older literature this is referred to as Borsche s method of carbazole synthesis (47CRV359). The use of the Japp-Klingemann method with an a -hydroxymethylenecyclohexanone as the substrate can provide... 

Aromatizations play a particularly prominent role in the synthesis of carbazoles since both the Fischer cyclization (Borsche s method) of cyclohexanones (Section 3.06.3.4.2) and the cycloaddition of 2-vinylindole (Section 3.06.6.1) yield tetrahydrocarbazoles. Both catalytic dehydrogenation over palladium/carbon catalyst and dehydrogenation with chloranil have been employed to effect aromatization (80JA4772,79JOC4402). 

Modification for higher molecular indoles Comparison of steric hindrance on the Fischer indole ring synthesis and the Pfitzinger-Borsche quinoline ring synthesis s. 4, 843... 

The Borsche-Drechsel carbazole synthesis is simply a Fischer indoUzation involving cyclohexanones, followed by oxidation of the tetrahydrocarbazole to a carbazole [144-147]. For reviews, see Campbell and Barclay [148] and Fultz [149]. Examples appear in the Applications section. 

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