Methyl carbazole-3-carboxylate

In 1988, Furukawa et al. reported the isolation of 3-formylcarbazole (3) from the root bark of M. euchrestifolia (22). Three years later, McChesney and El-Feraly isolated 3-formylcarbazole (3), along with methyl carbazole-3-carboxylate (4), from the roots of Clausena lansium (23). The roots of this ornamental tree are used in traditional medicine in Taiwan to treat bronchitis and malaria (23). In 1992, Bhattacharyya et al. described the isolation and structural elucidation of 3-formylcarbazole (3) from G. pentaphylla (24). 

In 2003, Sunthitikawinsakul et al. described the anti-mycobacterial activity of various 3-methylcarbazole derivatives, including 3-formylcarbazole (3), methyl carbazole-3-carboxylate (4) (see Scheme 2.2), clausine K (clauszoline-J) (51) (see Scheme 2.11), and 7-methoxymukonal (68) (see Scheme 2.14) against Mycobacterium tuberculosis H37Ra. Except for clausine K (clauszoline-J) (51), all of these alkaloids also showed anti-fungal activity against Candida albicans (442). In 2005, Eranzblau et al. reported the in vitro anti-TB activity of various carbazole derivatives such as 3-formylcarbazole (3), methyl carbazole-3-carboxylate (4) (see Scheme 2.2), lansine... 

Carbazoles can be synthesized by applying the Fischer cyclization to cyclohexanone hydrazones and then aromatizing the tetrahydrocarbazole product <88JHC671, 89JHC1213,93T1223>. An example is the synthesis of methyl carbazole-l-carboxylate (Equation (44)). 

One year later, we extended the aforementioned palladium(II)-catalyzed approach to a series of 6-oxygenated carbazole alkaloids, glycozoline (86), glycozolinine (glycozolinol) (91), glycomaurrol (92), micromeline (100), and methyl 6-methoxycarbazole-3-carboxylate (104) (547). The palladium(0)-catalyzed coupling of 4-bromoanisole (670) and p-toluidine (1028), followed by palladium(II)-catalyzed oxidative cyclization, afforded directly glycozoline (86). 

The preparatively useful and simple N-alkylation procedure that utilizes a combination of carboxylic acid and sodium borohydride has been applied to carbazole giving an efficient 9-ethylation. Also of preparative importance is the use of thallous ethoxide as base in dimethylformamide-ether 9-methyl-, 9-ethyl-, n-propyl-, n-butyl-, benzyl-, and n-allylcarbazoles were efficiently produced, as well as 9,9 -dicarbazolylalkanes using C3, C4, and Cg dihalides. 2-Acetyl- and 2-vinylcarbazole were also efficiently 9-ethylated by this route. Another more recent approach to N-alkylation of carbazole utilizes potassium terf-butoxide in the presence of a catalytic quantity of 18-crown-6 9-methylcarbazole was prepared in high yield. ... 

Carboxylation of carbazol-9-ylpotassium gave a moderate yield of the 3-carboxylic acid. The Kolbe-Schmidt carboxylation of 2-hydroxycarba-zole gave the 1-acid (50%) and the 3-acid as a minor product (12%). " Lithiation ° of 9-methyl- or 9-ethylcarbazole and carboxylation gave the 1-carboxylic acids. 

An independent synthesis of ellipticine follows, in its initial stages, the first olivacine synthesis reported in Section VII, C. Instead of the mono-methylcyanophenylhydrazine (CCLXII), a corresponding dimethyl compound, 3-cyano-2,5-dimethylphenylhydrazine (CCXCI-A), was employed as starting material. As far as the ester, methyl 1,4-dimethyl-carbazole-2-carboxylate (CCXCI-B), the two syntheses are parallel. Ring D was then built up, however, by the series of reactions,... 

Preparation of ll-methoxy-5H-benzo[b]carbazole-l-carboxylic acid, methyl ester... 

Our palladium-catalyzed approach for the construction of the carbazole framework led to the 6-oxygenated tricyclic carbazole alkaloids glycozoline (128), methyl 6-methoxycarbazole-3-carboxylate (133), glycomaurrol (135) and micromeline (130), as well as to the furo[2,3-c]carbazole alkaloid eustifoline-D (132) (Scheme 29) [149]. Palladium-catalyzed coupling of p-bromoanisole (125) and p-toluidine (126) as the first step led almost quantitatively to the diarylamine 127. Oxidative cyclization of intermediate 127 using 0.1 equiv. of palladium(ll) acetate in the presence of an excess of copper(ll) acetate provided glycozoline... 

Further oxidation of the formyl group using Corey s conditions by treatment with manganese dioxide and potassium cyanide in methanol afforded methyl 6-methoxycarbazole-3-carboxylate (133), which is a naturally occurring carbazole alkaloid. Alternatively, compound 129 can be regioselectively bromi-nated at the 5-position. Subsequent cleavage of the methyl ether and prenylation at C-5 with the dimeric 7i-prenylnickel bromide complex afforded micromeline... 

Recently, palladium(II)-catalyzed arylation/carboxylation reactions were reported for the synthesis of carbazoles starting from 2-alkenyl indoles. These reactions employ the electron-rich C-3 carbon atom of the indole nucleus as carbon nucleophile in cyclization/carboalkoxylation reactions. The conditions that proved effective for 2-(2,3 or 5-alkenyl)-3-unsubstituted indoles are similar to those reported for the cyclization ofalkenes and alkynes bearing tethered heteronucleophiles. In particular, the best results has been obtained using PdCl2(CH3CN)2, CuCl2 in methanol under CO (latm). Under these conditions methyl (9-methyl-2,3,4,9-tetrahydro-4-carbazolyl)acetate 86 was isolated in 94% yield (Scheme 13.53) (100,101]. 

Several copolymers of carbazole-containing poly-(meth)acrylates with electron-accepting comonomers have been reported. So 2-(V-carbazolylyl)ethyl acrylate has been copolymerized with 2-(2-carboxyl-4,5,7-trinitrofluorenyl)ethyl acrylate [169] (12a) and 2-(3,5-dinitrobenzoyloxy)ethyl methacrylate [170] (12b). 2-(3,5-Dinitrobenzoyloxy)ethyl acrylate (12c) has been copolymerized with l-(3-(9-methylcarbazolyl)methyl acrylate [171,172]. Due to the inhibition of radical polymerization by acceptor monomers with nitro... 

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