Carbazoles derivatives

Aminomethylindoles are particularly important synthetic intermediates. 3-Dimethyl-aminomethylindole (gramine) (153) and especially its quaternary salts readily undergo displacement reactions with nucleophiles (Scheme 60). Indole-2,3-quinodimethanes, generated from 2-methylgramine as shown in Scheme 61, undergo intermolecular cycloaddition reactions with dienophiles to yield carbazole derivatives (82T2745). 

Transition metal-mediated syntheses of carbazole derivatives 95MI6. 

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. 

Shortly thereafter, the first synthesis of the parent system 1 was reported, wherein Fischer indolization involving the carbazole derivative 12 furnished the desired product in 51% yield (Scheme 2). This achievement was correlated neatly with an alternative synthesis of 1 in 45% yield via the reaction of 1,2-cyclohexanedione mraiophenyUiydrazone and rtienylhydrazine in refluxing acetic acid, followed by treatment of the mixture with hot concentrated hydrochloric acid (57CIL363). 

The preparaticai of 2 from the carbazole derivative 112 provided yet another alternative route (Scheme 14). The precursor 113 was obtained from 112 by heating with phenylhydrazine in ethanol in the presence of acetic acid, followed by... 

Further investigations revealed that the disubstituted indolo[3,2-fl]carbazoles 117a-b may be conveniently obtained in moderate yields simply by heating 115 with dimethyl or diethyl acetylenedicarboxylate in xylene, while the use of lower-boiling solvents (benzene, toluene) led to the formation of the presumed intermediate Michael adducts 118a-b as the major products. The reaction of 115 with 2-chloroacrylonitrile furnished the indolo[3,2-fl]carbazole derivative 119 where aromatizaticRi did not take place (99T2371). 

Recently, the protected dimethoxy derivative 152 has been isolated in 70% yield from the Boc-protection of a nonseparable product mixture of the corresponding 2,8-dimethoxyindolo[3,2-h]carbazole 153 and the isomeric indolo[2,3-c]carbazole derivative (cf. Section VI) obtained by a double Fischer cycUzation using PPSE (00MI2). 

The dimerization reactions of 2-vinylindoles and their alcohol precursors have also been explored, giving rise to the formation of several dimeric structures, such as the 6,12-dihydroindolo[3,2-h]carbazole derivative 160, which was obtained on dimerization of 2-(a-hydroxyethyl)indole under acidic conditions (71JOC1759). 

Studies on the Bischler-Napieralski cyclization of A -acetyltryptamine in the presence of indole have led to the isolation of numerous products, among which the indolocarbazole 186 could be found in 3.5% yield. This outcome was rationalized as a result of the intermediacy of a spiroindolenine species formed under these conditions [89H(28)175]. During detailed studies on the polymerization of indole, formation of a low yield of the related indolo[3,2-h]carbazole 187 was discovered in the product mixture originating from the treatment of indole with p-toluenesulfonic acid at elevated temperature [88JCS(P1)2387]. In an investigation of the condensation of p-benzoquinone with 4-substituted anilines, an indolo[3,2-h]carbazole derivative has been reported to be formed in 2% yield (80JOC1493). 

A few examples of the photocyclization of A,iV-diarylamines or related species have been applied to the synthesis of spirocyclic indoline precursors <96TL37> and carbazole derivatives <96SC657, 96JCS(P1)669>. 

Petrillo reported that the bis-acetoxymethylpyrrole 83 undergoes a sequential Diels-Alder reaction of the in situ generated 2,3-dimethylpyrrole with carbodienophiles (such as maleic anhydride, maleimide, ethyl maleate, fumaronitrile, and ethyl acrylate) to afford the octahydrocarbazoles 84 which can be oxidized with DDQ to the corresponding carbazole derivatives . 

As demonstrated in previous sections, the carbazole unit was introduced as a pendant group or as a chain member in major classes of EL polymers such as PPVs (95-105,141,177, 190) and PFs (62, 63, 242-245). A variety of 2,7-carbazole-derived polymers with different conjugated units, such as 2-alkoxy- and 2,5-dialkoxy-l,4-phenylene (549) and l,l -binaphtha-lene-6,6 -diyl (550 [658]), 2,5-pyridine (551), 2,7-fluorene (245 [345,346]), 2,5 -bithiophene (554 [345]), 5,8-quinoxaline (552), quinquethiophene-SjS -dioxide (450 [550]), 2,5-thiophene (553), 2,5-furan (555), and acetylene (556 [659]) were reported by Leclerc and coworkers... 

J.-H. Lee, J.-W. Park, and S.-K. Choi, Synthesis and electroluminescent property of a new conjugated polymer based on carbazole derivative poly(3,6-lV-2-ethylhexyl carbazolyl cyanoter-ephthalidene), Synth. Met., 88 31-35, 1997. 

J.-F. Morin, S. Beaupre, M. Leclerc, I. Levesque, and M. D lorio, Blue light-emitting devices from new conjugated poly(iV-substituted-2,7-carbazole) derivatives, Appl. Phys. Lett., 80 341-343, 2002. 

A new branched carbazole derivative with phenyl ethylene moieties attached, l,3,5-tris(2-(9-ethylcarbazyl-3)ethylene)benzene (TECEB, 41) (Scheme 3.15), was prepared as a HTM for OLEDs [86], TECEB has a HOMO energy level of —5.2 eV and hole-drift mobility of 1(T 4 cm2/(V s), comparable to NPD. The device performance (maximum luminance of about 10,000 cd/m2 and current efficiency of 3.27 cd/A) in a standard HTL/tris-(8-hydroxyquino-line) aluminum double-layer device is also comparable to NPD, but TECEB has a higher Tg (130°C) and its ease of synthesis is superior to NPD. Distyryl units linked to a TPD derivative, A, A"-bis(4-(2,2-diphenylethenyl)-phenyl)-jY,jV -di(p-tolyl)-bendidine (DPS, 42) (Scheme 3.15), reported by Yamashita and coworkers, showed good hole transport properties and improved thermal stability compared with the parent TPD [87]. 

The total synthesis of the carbazomycins emphasizes the utility of the iron-mediated synthesis for the construction of highly substituted carbazole derivatives. The reaction of the complex salts 6a and 6b with the arylamine 20 leads to the iron complexes 21, which prior to oxidative cyclization have to be protected by chemoselective 0-acetylation to 22 (Scheme 13). Oxidation with very active manganese dioxide followed by ester cleavage provides carbazomycin B 23a [93] and carbazomycin C 23b [94]. The regioselectivity of the cyclization of complex 22b to a 6-methoxycarbazole is rationalized by previous results from deuterium labeling studies [87] and the regiodirecting effect of the 2-methoxy substituent of the intermediate tricarbonyliron-coordinated cyclo-hexadienylium ion [79c, 79d]. Starting from the appropriate arylamine, the same sequence of reactions has been applied to the total synthesis of carbazomycin E (carbazomycinal) [95]. 

The major product (21-37%) from the reaction of benzyne with N-phenylpyrrole is the 2 1 adduct (167), the formation of which is explicable in terms of the cyclization of either one of two intermediate zwitterions, 165 or 166. Alternatively, prototropic shift within the intermediate (166) accounts for the formation of the a-naphthylamine (147) (4-6% yield). Other benz[o]carbazole derivatives (168 and 169)... 

In 1997, Chakrabarty et al. reported the isolation of 9-carbethoxy-3-methylcarba-zole (5) and 9-formyl-3-methylcarbazole (6) from the roots of M. koenigii (17). These metabolites are the first 9-formyl and 9-carbethoxy carbazole derivatives obtained from plant sources. 9-Formyl-3-methylcarbazole (6) showed weak cytotoxicity against both mouse melanoma B16 and adriamycin-resistant P388 mouse leukemia cell lines. The structural assignment of these two alkaloids was based on the IR- and H-NMR spectra which were lacking any signal of an NH group. Additional structural support for 9-carbethoxy-3-methylcarbazole (5) was provided by the similarity of the UV absorption spectrum with that of a synthetic sample, obtained by reaction of 3-methylcarbazole with ethyl chloroformate in the presence of base. Further structural support for 9-formyl-3-methylcarbazole (6) was derived from a comparison of the UV spectrum and the IR carbonyl absorption (1696 cm ) with those of an authentic sample of 9-formyl-3-methylcarbazole (1700 cm ), prepared by the treatment of 3-methylcarbazole (2) with 98% formic acid (17) (Scheme 2.3). 

C-8. The spectroscopic data, supported by transformation into known carbazole derivatives, led to structure 129 for heptazolicine (Scheme 2.24). 

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