Benzocarbazole

The Bucherer carbazole synthesis was first demonstrated when 7 was heated in the presence of phenylhydrazines 8, sodium hydroxide and sodium bisulfite after acidic work-up, the benzocarbazole product 9 was isolated (-70% yield). When 2-naphthol was used the reaction was significantly slower with the yield of benzocarbazole being only 46% after several days at 130 °C Bucherer and co-workers investigated this reaction extensively concluding, incorrectly, that intermediate products were probably carbazole-Al-sulfonic acids due to the ease with which they lost the sulfonic acid residues to yield benzocarbazoles. 

When naphthyl amines e.g. 23) are used in the Bucherer carbazole synthesis, they are converted by the catalytic action of aqueous bisulfite into tetralonesulfonic acid derivative 13 by the Bucherer reaction. Addition of NaHSOs gives an enamine, which tautomerises to the imine 24 24 is hydrolysed to keto form 13 and subsequent Bucherer carbazole synthesis follows to afford the benzocarbazole product 20. ... 

Most of the early applications of palladium to indole chemistry involved oxidative coupling or cyclization using stoichiometric Pd(II). Akermark first reported the efficient oxidative coupling of diphenyl amines to carbazoles 37 with Pd(OAc)2 in refluxing acetic acid [45]. The reaction is applicable to several ring-substituted carbazoles (Br, Cl, OMe, Me, NO2), and 20 years later Akermark and colleagues made this reaction catalytic in the conversion of arylaminoquinones 38 to carbazole-l,4-quinones 39 [46]. This oxidative cyclization is particularly useful for the synthesis of benzocarbazole-6,11-quinones (e.g., 40). 

In the past decade, a few examples of benzoannulated carbazole ring systems were found in nature as marine products. In 1993, Chan et al. reported a novel marine benzocarbazole alkaloid, purpurone (281) from the marine sponge lotrochota sp. in its racemic form. Purpurone, as indicated by its name, is purple in color. This represents the first example of a benzocarbazole alkaloid with a biphenylene quinone methide functionality. The isolate showed ATP-citrate lyase (ACL) inhibitory activity (247). 

In 1970, Rice et al. studied a diverse range of 3-substituted 1,2,3,4-tetrahydrocarba-zole derivatives in a preliminary pharmacological screening for general stimulation, depression, and autonomic activity, and found that 3-carboethoxy-9-(3-dimethyl-aminopropyl)-l,2,3,4-tetrahydrocarbazole (461) exhibited growth inhibition at a concentration of 1 gg/mL in mammary carcinoma tissue (400). These studies were based on the carcinogenic activity observed for the bis-angular bis-benzocarbazoles reported by Buu-Hoi et al. (401). 

The Bucherer carbazole synthesis involves the treatment of a naphthyl alcohol (525) or a naphthylamine (526) with phenylhydrazine (524) in the presence of aqueous sodium bisulfite to afford, after work-up, benzocarbazole (527) (508). 

Benzocarbazole and derivs 2 B66 dinitrobenzocarbazole 2 B66 mononitrobenzocarbazole 2 B66 nitrobenzocarbazole 2 B66 pentanitrobenzocarbazole 2 B66... 

Pentanitrobenzocarbazole, ClgHgN6O10 mw 442.18, N 19-01%. One isomer, x,x,x,x,x-Penta-nitro-2,3-benzocarbazole is described in the literature. The compd is in the form of golden-yel lfts, mp 256° nearly insol in most org solvents. Was prepd by heating 2,3-benzocarbazole or x,x -dinitro-2,3 benzocarbazole with mixed nitric -sulfuric acid. Its expl props were not investigated Refs l)Beil 20,(179) 2)F.Kehrmann et al,Ber 46,3716(1913)... 

A complementary access to extended indole and carbazole systems is based on the thermal intramolecular benzannulation of ortfio-al kyn ylan i 1 i nocarbene complexes or on a photo-induced benzannulation of phenylpyrrolylcarbene complexes. The first example involves an intramolecular access to the carbazole skeleton. Refluxing a solution of orflio-alkyn yl phen yl amino carbene complex 109 in acetonitrile gave a 63 % yield of benzocarbazole 110. Less strongly coordinating solvents (TBME, THF, or di-n-butyl ether) or other substituents less bulky than 2,4,6-trimethylphenyl (for example, phenyl or 4-methylphenyl) led to a considerably reduced yield (Scheme 39) [83]. 

C17H13N 6-methyl-3,4-benzocarbazole 21064-50-6 670.15 60.450 2 30076 C17H1802 benzyl isoeugenol ether 120-11-6 425.15 36.741 2... 

Reductive cyclization of the nitroarylethylisoquinolines (40 R = H) and (40 R = Me) with triethylphosphite gave the benzimidazoisoquinoline benzacridine (42) respectively (Scheme 5). These products were each synthesized by independent routes. The formation of (42) is analogous to the formation of a benzocarbazole from 6-nitrolaudanosine (c/. Vol. 1). The reactions of various bromaralkylisoquinolines with methylsulphinyl carbanion are described in Section 7. 

A, few isochroman-3-ones occurs in nature The importance of isochroman-3-ones however is because they are valuable intermediates for the synthesis of isoquinolines. A most interesting use of isochroman-3-ones is that they provide benzocyclobutenes which are valuable synthons for berbines, spiro-benzylisoquinolines, 3-aryl isoquinoline, benzophenanthridines, benzocarbazoles, yohimbin, tetracycline, steroids etc. 

The reaction can be extended to benzo-condensed aminomethylenecyclo-hexanone " and cyclopentanone derivatives. Af-arylcycloheptindolones, are accessible in a good yield. Enaminones in the indanone series react to give benzocarbazoles, which are readily oxidized in one step to benzocarbazolquinones (equation 159), the derivatives of which bear high cytostatic activity. ... 

A deviation from the simple mechanism in Scheme 52 was observed with 2-pyridyl(2-naphthyl)carbene (282), from which a benzocarbazole, a pyrido[2,l-a]isoindole, and a benzindenopyridine were obtained (Scheme 53).232... 

---