Carbazole-1-carboxylic acid

The cyclodehydrohalogenation of 2-halo-Ar,AT-diarylamines is analogous to the classical Heck reaction [114-116] and represents a palladium(0)-catalyzed process (Scheme 28). Cyclization of the diarylamine 78 with a palladium(O) catalyst, generated in situ by reduction of palladium(II) with triethylamine, affords carbazole-1-carboxylic acid 79 in 73% yield [122]. 

The anti-inflammatory properties of several carbazole derivatives have attracted widespread attention. Some acidic tetrahydrocarbazoles have been shown to have anti-inflammatory activity (451). Among these derivatives, l-ethyl-8-M-propyl-1,2,3,4-tetrahydrocarbazole-l-acetic acid (491) was found to be a novel antiinflammatory agent (451), and 6-chloro-l,2,3,4-tetrahydrocarbazole-2-carboxylic acid (492) was clinically active in the treatment of acute gout (452). 

Two years later, the same group reported a formal synthesis of ellipticine (228) using 6-benzyl-6H-pyrido[4,3-f>]carbazole-5,ll-quinone (6-benzylellipticine quinone) (1241) as intermediate (716). The optimized conditions, reaction of 1.2 equivalents of 3-bromo-4-lithiopyridine (1238) with M-benzylindole-2,3-dicarboxylic anhydride (852) at —96°C, led regioselectively to the 2-acylindole-3-carboxylic acid 1233 in 42% yield. Compound 1233 was converted to the corresponding amide 1239 by treatment with oxalyl chloride, followed by diethylamine. The ketone 1239 was reduced to the corresponding alcohol 1240 by reaction with sodium borohydride. Reaction of the alcohol 1240 with f-butyllithium led to the desired 6-benzylellipticine quinone (1241), along with a debrominated alcohol 1242, in 40% and 19% yield, respectively. 6-Benzylellipticine quinone (1241) was transformed to 6-benzylellipticine (1243) in 38% yield by treatment with methyllithium, then hydroiodic acid, followed... 

One of the earliest azaheterocyclic systems to be investigated for reaction with n-BuLi was carbazole, but only a very poor yield of the 1-carboxylic acid was obtained after treatment with carbon dioxide (Scheme 30)(36JOC146). 

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 efficient chemical process for closing a diphenylamine is that using palladium(II) acetate (2 mol for substrates carrying electron-withdrawing groups) in acetic acid-methanesulfonic acid. Carbazole formation has been achieved with alkyl-, halo-, nitro-, and carboxyl-substituted diphenylamines. 1-Chlorocarbazole and carbazol-l-yl carboxylic acid as examples were efficiently prepared. - This is probably the best method now available for cyclizing diphenylamines. 

A number of related reactions are worthy of mention. Benzanilide (334) is converted into phenanthridone (335) by irradiation in benzene in the presence of iodine.362 Cyclodehydrogenation is also observed in the anilides of indole-2-carboxylic acid and indole-3-carboxylic acid on irradiation in acetone.363 Irradiation of diphenyl-amine304 and certain of its JV-substituted derivatives365 yields the corresponding carbazole. The mechanism of this reaction differs from... 

On the pages which follow, general methods are illustrated for the synthesis of a wide variety of classes of organic compounds including acyl isocyanates (from amides and oxalyl chloride p. 16), epoxides (from reductive coupling of aromatic aldehydes by hexamethylphosphorous triamide p. 31), a-fluoro acids (from 1-alkenes p. 37), 0-lactams (from olefins and chlorosulfonyl isocyanate p. 51), 1 y3,5-triketones (from dianions of 1,3-diketones and esters p. 57), sulfinate esters (from disulfides, alcohols, and lead tetraacetate p. 62), carboxylic acids (from carbonylation of alcohols or olefins via carbonium-ion intermediates p. 72), sulfoxides (from sulfides and sodium periodate p. 78), carbazoles... 

The results of the infrared analysis are presented in Table VI. These results show that carboxylic acids and phenols are found only in the acid concentrates. Carboxylic acids are concentrated in the polar acid subfractions III and IV while phenols are concentrated in subfraction II. Carbazoles, ketones, and amides are found in all three major nonhydrocarbon fractions. The appearance of the same compound type in several fractions may arise from differences in acidity or basicity that are caused by the hydrocarbon portion of the molecule. Multifunctionality could also be a factor in the distribution of compound types among the fractions. The 1695 cm"1 band was assigned to ketones on the basis of work... 

Thus, the hydrodesulfurization process is a very complex sequence of reactions due, no doubt, to the complexity of the feedstock. Furthermore, the fact that feedstocks usually contain nitrogen and oxygen compounds (in addition to metal compounds) increases the complexity of the reactions that occur as part of the hydrodesulfurization process. The nitrogen compounds that may be present are typified by pyridine derivatives, quinoline derivatives, carbazole derivatives, indole derivatives, and pyrrole derivatives. Oxygen may be present as phenols (Ar-OH, where Ar is an aromatic moiety) and carboxylic acids (-C02H). The most common metals to occur in petroleum are nickel (Ni) and vanadium (V) (Reynolds, 1997). 

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

Whereas N-phenylindoles are reduced to the corresponding dihydroindoles with Na/NHs (equations 46 and 47)8 -89 and indole-2-carboxylic acid is reduced to the indoline with Li/NH3/PhNH2 (equation 48), indole itself is reduced to 4,7-dihydroindole (Li/NHs, MeOH) in 51% yield. These latter conditions also reduce carbazole to 1,4-dihydrocarbazole in 73% yield. ... 

Separation of the Asphaltene. Table I shows the weight percent of the asphaltene fractions and subfractions produced by the separation scheme. The acid fraction, amounting to 81% of the total asphaltene, is the largest fraction isolated by the separation scheme. The primary prerequisite for a compound type to be defined as an acid by the anion, resin appears to be the ability of the compound type to hydrogen bond to the anion resin. Earlier work with distillates and residues identified compound types such as carboxylic acids, phenols, amides, and carbazoles as the major components of an acid fraction (6). Table I shows that Subfraction 3, the subfraction containing the strongest (most readily hydrogen bondable) acids, is more than half of the total acid fraction. 

In this discussion, polar compounds are defined as those that are capable of hydrogen bonding with other polar molecules. Thus, carboxylic acids, phenols, carbazoles, and amides are polar molecules. In addition, molecules such as pyridine benzologs are polar because they can hydrogen bond with carboxylic acids and phenols. Nonpolar molecules are those such as normal alkanes, cyclic alkanes, and aromatic hydrocarbons— molecules that normally do not associate with hydrogenbonding molecules. 

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