Alkylation of carbazoles

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. ... 

The most straightforward and efficient method now available for N-alkylation of carbazoles is the catalytic two-phase process utilizing a benzene solution of the carbazole, 50% aqueous sodium hydroxide, and a catalytic quantity of a tetraalkylammonium salt (benzyltrimethylammo-nium chloride has been used) with the requisite halide. - The efficient and simple formation of 9-methyl, 9-ethyl, 9-n-propyl, 9-n-butyl, and 9-benzyl derivatives has been described. ... 

Alkylation of carbazole has not been studied systematically but isolated preparative examples suggest that N- alkylation can be carried out as for pyrroles and indoles. No complication from competing carbon alkylation occurs. N- Alkylation of the anion of isoindole does not seem to have been investigated. One might expect serious competition from C- alkylation because of the favorable benzenoid conjugation of the resonance structure with charge on carbon (equation 161). 

Bogdal, D., Pielichowsk, J., and Jaskot, K. 1997. New synthesis method of A -alkylation of carbazole under microwave irradiation in dry media. Synthetic Communications, 27 1553-60. 

Alkylation of the dimethylpiperazine 12 with 3-chloropropanol followed by treatment of the product 13 with thionyl chloride gives the halide 14. Alkylation of the anion from carbazole (15) with that halide leads to the tricyclic antipsychotic agent rimcazole (16) [4]. 

Fuostifoline (47), a furo[3,2-a]carbazole, was isolated from Murraya euchrestifolia. Timdri s total synthesis of 47 commenced with alkylation of bromocresol 43 with bromoacetaldehyde diethyl acetal and P4Oio-promoted cyclization to furnish 5-bromo-7-methylbenzofuran (44) [47]. The Suzuki coupling of boronic acid 45, derived from 44, with o-bromonitrobenzene yielded biaryl 46. Nitrene generation, achieved via deoxygenation of nitro compound 46 using triethyl phosphite, was followed by cyclization to fuostifoline (47). 

A. Iraqi and I. Wataru, Preparation and properties of 2,7-linked A-alkyl-9JL-carbazole main-chain polymers, Chem. Mater., 16 442M48, 2004. 

Flexible and semiflexible chains for the connection of carbazole units have been used by Braun et al. [43, 44]. However, it can clearly be seen that introducing longer alkyl spacers lowers the Tg. In addition to carbazoles, the... 

Alkylation of pyrroles, indoles and carbazoles under liquidiliquid two-phase conditions with an added organic solvent... 

The fusion of powdered potassium hydroxide and carbazole together at 220-260°C has been often used for the preparation of the potassium salt of carbazole, the salt then being utilized in hydrocarbon solvent powdered potassium hydroxide was shown " to be better for this purpose than strong aqueous sodium hydroxide. Many 9-alkylations have been conducted in this way including preparations of dicarbazol-9-ylalkanes [29 R = (CH2)3 g-carbazol-9-yl] (using the corresponding dihalides), 9-(2,3-epoxyprop-l-yl) O / ... 

Iron acetylacetonate catalyzed the introduction of a range of alkyl groups onto the carbazole nitrogen using the corresponding halides. A small yield of 9-(2-cyanoethyl)carbazole was obtained by light catalyzed addition of carbazole to acrylonitrile. ... 

Ethynylcarbazole was apparently formed by sodamide treatment of 9-dichlorovinylcarbazole (97) and zinc reduction of 97 gave 98. Where no reaction occurred with the Z isomer, 99 gave the dimer 100 with boron trifluoride the process presumably involves Lewis acid-catalyzed alkylation of one double bond by another double bond, complexed to boron trifluoride, followed by intramolecular Friedel-Crafts type alkylation at the carbazole 1-position. ... 

A mixture of carbazol (0.84 g, 5.0 mmol), alkyl halide (7.5 mmol), tetrabutylam-monium bromide - TBAB (0.17 g, 0.50 mmol), and potassium carbonate (2.8 g, 20 mmol) was heated in a domestic microwave oven in an open Erlenmeyer flask for an appropriate time. After cooling down, the reaction mixture was extracted with CH2CI2 (2x25 mL). Then the extract was dried with MgSCXt, filtered, and the solvent was evaporated to dryness. The solid material was purified by means of flash chromatography to afford the desired /V-alkylcarbazole, yield 32-95%. 

More interesting for the synthesis of carbazoles is the photochemical reaction of non-halogenated A-arylenaminones which stereospecifically leads to carbazoles in high yield208 (equation 147). The enaminone -position may be alkylated as well209. 

Under microwave irradiation, carbazole reacted remarkably fast with a number of alkyl halides to give Af-alkyl derivatives of carbazole (82) (Bogdal et al., 1997). The reaction was carried out with high yields by simply mixing carbazole with an alkyl halide, which was adsorbed on potassium carbonate. A facile synthesis of a series of A-alkylpyrrolidino fullerenes (83) by phase transfer catalysis without solvent under microwave irradiation has been described by De la Cruz et al. (1998), while Adamczyk and Rege (1998) have illustrated the dramatic rate acceleration for A-sulfopropylation of heterocyclic compounds using 1,3-propane sultone under microwave irradiation affording the A-sulfopropylated compounds in 68-95% yield. 

N-Alkylation of lf/-pyrrole, indole and carbazole can be accomplished with benzyl halides (chloride and bromide) in acetonitrile and cesium fluoride/Celite employed as a solid base (Equation 12) <2001T9951>. The procedure is convenient and efficient, and generally gives rise to the N-alkylated products exclusively, in high yields (78-93%). 

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