Carbazole preparation

Typically, the reaetion would be carried out at 140°C in white spirit with potassium carbazole as a catalyst. Davidge ° has reported problems in polymerisation of V-vinyl carbazole prepared from carbazole obtained from coal tar, attributing this to the presence of sulphur. To overcome these problems carbazole has been prepared synthetically by reactions of cyclohexanone with... 

It is prepared by the nitration of carbazole preparation begins with sulfuric acid treatment until the compound becomes fully soluble in water, after which the sulfonic acid derivative is directly converted to the nitro compound by adding mixed acid without previous isolation. 

G. Inzelt. Formation and redox behaviour of poly carbazole prepared by electropolymerization of solid carbazole crystals immobilized on an electrode surface. J. Solid State Electrochem., 7(8) 503-510, August 2003. 

Although the cyclization of nitrenes to indoles via ortho-azidostyrenes justifiably is associated with Sundberg, several earlier workers described and studied this reaction. Notably, the researches of Smith [1-5], SmoUnsky [6-8], Abramovitch [9], Coffin and Robbins [10], and Isomura colleagues [11] describe the pyrolysis of ort/io-azidobiphenyls to carbazoles and, in a few cases, ort/io-azidostyrenes to indoles. A sampling of these pre-Sundberg reactions from the work of Smith and coworkers is shown in Scheme 1. The typical solvent used was kerosene, and the conversion of azides to carbazoles was also accomplished photochemically, albeit in lower yield. Other carbazoles prepared thermally were 1-4 in excellent yields. These workers also synthesized 4H-thieno[3,2-ii]indole (5) from 2-(o-azidophenyl)thiophene [3]. 

Several biologically and pharmacologically active compounds have been prepared from the condensation of the acid chloride of 1-naphthoxyacetic acid with carbazole, iadole, or pyrrole ia 2A[ NaOH solution ia ethanol (63). Also, naphthyloxy derivatives of imidazole, benzimidazole, and benzotriazoles have been synthesized and screened for their antimicrobial, analgesic, and antiinflammatory activities. 2-Naphthyloxy derivatives are comparatively more active than 1-naphthyloxy derivatives (64). 

Considerable progress has also been made with the alternative line of work, the search for a synthetic analgesic as effective as morphine and without its disadvantages. The work of the American Committee has shown that it is possible to produce analgesics with a dibenzofuran or carbazole nucleus in place of the phenanthrene or phcnanthrylene oxide nucleus of morphine and it is stated that synthetic products with analgesic potency equal to that of codeine have been prepared. In the 1938 report moderate analgesic potency was recorded for preparation No. 421, 9-methyl-2-(l-hydroxy-3-diethylamino)-propylcarbazole at 10 mgm. by injection. 

The Bucherer carbazole synthesis was pivotal in the preparation of the first hexahelicene 37a. Reaction of 2,7-dihydroxynaphthalene 35 with phenylhydrazine and sodium bisulfite afforded helicene 37a although in low yield. More recently, the synthesis was extended to the preparation of 37b using 2,5-dimethylphenylhydrazine 36b. ... 

The Graebe-Ullman carbazole synthesis has been enmloyed in the preparation of substituted carbolines, as well as indolo[2,3-i] quinolines, which are often difficult to synthesize via other approaches, for example, the Fischer indole process. 

The Combes reaction has been applied to the preparation of carbazoles related to eJJipticine. In that case, the imine was not formed separately nor purified yet the desired product 57 was isolated in 35%. ... 

Oddo reported that the organomagnesium derivatives of p3Trole, indole, skatole, and carbazole could be prepared in a single operation by mixing the parent heterocyclic compound with an alkyl halide and magnesium in anhydrous ether.The product formed was reported to be the same as that obtained by the more conventional procedure. However, this approach to the synthesis of the indole Grignard reagents does not seem to have been exploited in subsequent work. 

The first example of an indolo[2,3-a]carbazole derivative reported with a reasonably estabhshed structure was the mono N-methylated system 9, prepared via dehydrogenation with palladium on charcoal of the octahydro derivative 10, available via reaction of the aminocarbazole 11 with 2-hydroxycyclohexanone in the presence of a trace amount of anihnium bromide (Scheme 1). An approach toward the parent compound 1 using the same method has also been attempted, although without success (56JCS4783). The utility of this route is impaired by the complexity of the starting material, which requires multistep preparation, and the harsh conditions of the final step. 

The parent indolo[2,3-fl]carbazole (1) has also been the subject of a study probing its reactivity toward oxidizing agents. One of the substrates involved, namely 85 (prepared from 1 and 2,5-dimethoxytetrahydrofuran in the presence of acid), was subjected to treatment with m-chloroperbenzoic acid, to give the dione 86 as the major product and a sensitive compound assigned the hydroxy structure 87. A cleaner reaction took place when 85 underwent oxidation with tert-butyl hydroperoxide assisted by VO(acac)2, to produce 86 exclusively in 86% yield. Likewise, A,N -dimethylindolo[2,3-fl]carbazole furnished the dione 88 on treatment with this combination of reagents (96J(X 413). 

A synthesis of an indolo[3,2-fl]carbazole (2) was reported in 1951—the first preparation of a compound belonging to this class (Scheme 13). This was accomplished commencing with cyclohexanone, via conversion to the bishydrazone 108, which underwent Fischer indolization in glacial acetic acid to furnish the octahy-dro derivative 109. After a final dehydrogenation step, the desired product 2 was obtained (51JCS809). 

In an investigation into the synthetic utility of the oxyindole 122, a wide variety of benzo- and heterocyclo-fused indexes and carbazoles was prepared, e.g., the indolo[3,2-a]carbazole 123 (Scheme 16). Thus, when 122 was reacted with indo-lylacetonitrile 124 in the presence of a base, followed by heating with phosphoric acid, the indolocarbazole 123 could be isolated in good yield (99T11563). 

Another short protocol for preparation of 3 was recently presented by Knolker and Reddy, who devised a short sequence involving a double iron-mediated arylamine cyclization as the key step (Scheme 19). Thus, the reaction of m-phenylenediamine (140) with the tricarbonyliron-complexed cyclohexadienyl cation 141 yielded the complex 142, which was eventually transformed into indolo-[2,3-()]carbazole (3) via cyclization and dehydrogenation (98TL4007 00T4733). 

Similarly, iV,A/ -dimethyl-3,3 -bisindolylmethane (169) has been used in a related experiment, where treatment thereof with trifluoroacetic fflihydride (TFAA) in diethyl ether at room temperature yielded a mixture of products from which the trifluoromethyl-substituted indolo[3,2-b]carbazole 170 was isolated as the major pentacyclic component, accompanied by the hydroxy derivative 171 as well as small amounts of the indolo[2,3-h]carbazole 146 (Scheme 20). The precursor 169 could also be prepared in situ from A-methylindol-3-methanol under... 

Katritzky and co-workers have developed a methodology for the preparation of heterocyclo[h]-fused carbazoles from benzotriazole derivatives (Scheme 26). Using this approach, W,iV -dimethylindolo[3,2-h]carbazole (150) was prepared via a thermally induced cyclization of the benzotriazole-containing precurscM 196 (95JOC3707). 

In an effort toward indolo[3,2-h]carbazoles based on Lewis acid-assisted dimerization of benzotriazole derivatives, the necessary starting materials 197 were prepared in good yields from 1-propargylbenzotriazole and 2-iodoaniline followed by alkylation. In the ensuing dimerization step, compounds 197 were treated with zinc chloride in refluxing dichlorometane to afford the indolo[3,2-h]carbazoles 199 or the dihydro derivatives 198 (Scheme 27). Under similar conditions 197, where R = = H, did not undergo dimerization, which suggests that the alkyl... 

The most recent synthetic efforts in this area have focused on the preparation of mono- and diformyl-substituted indolo[3,2-l)]carbazoles 202 and 203, which are potent aryl hydrocarbon receptor (AHR) ligands (cf. Section V,C). 

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