Carbazoles acidity

If cold saturated ethanolic solutions of the recrystallised tetrahydrocarbazole and of picric acid are mixed and stirred, the chocolate-brown picrate of the carbazole slowly crystallises. After it has been filtered off at the pump, washed with a small quantity of ethanol, and dried, it has m.p. 145-146°. 

Dewar and his co-workers, as mentioned above, investigated the reactivities of a number of polycyclic aromatic compounds because such compounds could provide data especially suitable for comparison with theoretical predictions ( 7.2.3). This work was extended to include some compounds related to biphenyl. The results were obtained by successively compounding pairs of results from competitive nitrations to obtain a scale of reactivities relative to that of benzene. Because the compounds studied were very reactive, the concentrations of nitric acid used were relatively small, being o-i8 mol 1 in the comparison of benzene with naphthalene, 5 x io mol 1 when naphthalene and anthanthrene were compared, and 3 x io mol 1 in the experiments with diphenylamine and carbazole. The observed partial rate factors are collected in table 5.3. Use of the competitive method in these experiments makes them of little value as sources of information about the mechanisms of the substitutions which occurred this shortcoming is important because in the experiments fuming nitric acid was used, rather than nitric acid free of nitrous acid, and with the most reactive compounds this leads to a... 

Folyphosphoric acid trimethylsilyl ester (PPSE)[1] can be used in sulfolane, CH,Cl2 or nitromethane. It is similar to polyphosphoric acid but the overall conditions arc milder and the work-up more convenient. PPSE has been used in the cydization of ris-arylhydrazones of cyclohexane-l,2-diones to give indolo[2,3-a]carbazole analogues[2],... 

Pyrano[3,4-b]indol-3-ones are the most useful equivalents of the indol-2,3-quinodimethane synthon which are currently available for synthetic application. These compounds can be synthesized readily from indole-3-acetic acids and carboxylic anhydrides[5,6]. On heating with electrophilic alkenes or alkynes, adducts are formed which undergo decarboxylation to 1,2-dihydro-carbazoles or carbazoles, respectively. 

Naphthalene, anthracene, carbazole [86-74-8] phenol [108-95-2] and cresyUc acids are found in the tar. Phenol and cresyUc acids are useful as chemical and resin intermediates. The aromatic chemicals are useful in the manufacture of pharmaceuticals, dyes, fragrances, and pesticides. Various grades of pitch are made from residues of tar refining. Coal-tar pitch is used for roofing and road tar, and as a binder mixed with petroleum coke to produce anodes for the aluminum industry. 

Several biologically and pharmacologically active compounds have been prepared from the condensation of the acid chloride of 1-naphthoxyacetic acid with carbazole, iadole, or pyrrole ia 2A[ NaOH solution ia ethanol (63). Also, naphthyloxy derivatives of imidazole, benzimidazole, and benzotriazoles have been synthesized and screened for their antimicrobial, analgesic, and antiinflammatory activities. 2-Naphthyloxy derivatives are comparatively more active than 1-naphthyloxy derivatives (64). 

No oxidizing agent is required for the sulfuric acid promoted cyclization of iV,iV-diphenyl-hydroxylamine to carbazole (13CB3304). The parallel conversion of diphenyl sulfoxide and diphenyl selenoxide to dibenzothiophene (23CB2275) and dibenzoselenophene (39CR(199)53l) is effected by treatment with sodamide. 

While this work was in progress Spath and Bretschneider showed that strychnine, on oxidation with permanganate in alkaline solution, furnished W-oxalylanthranilic acid (VII), brucine yielding oxalyl-4 5-dimethoxy-anthranilic acid, the latter observation providing confirmation of the evidence previously adduced that the two methoxy-groups in brucine are in the oj Ao-position relative to each other as indicated by Lions, Perkin and Robinson. The results so far considered indicate the presence in brucine and strychnine of the complex (VIII), which can be extended to (IX) if account is taken of the readiness with which carbazole can be obtained from strychnine and brucine and certain of their derivatives by decomposition with alkali at temperatures ranging from 200° to 400°, Knowledge of the structure of the rest of the molecule is mainly due to the results of the exhaustive study by Leuchs and his pupils of the oxidation... 

Colour Reactions. Rochelmeyer (1939) has provided a list of colour reactions given by solasodine and solasodiene (solanosodine), with reagents usually applied to the sterols, and Briggs et al. have found that when concentrated sulphuric acid (1 mil) is carefully added to a solution of solasonine or solasodine in hot alcohol (1 mil) a characteristic, intense, greenish-yellow fluorescence is produced, a reaction which is not given by solanine or solanidine. They have also found that intense colours are formed when solasonine or solasodine is mixed with resorcinol, or one of a variety of aldehydes, and boiled with concentrated hydrochloric acid. Colours are also produced with this test by cholesterol, digitonin, jacobine carbazole, pyrrole, or nicotine, the most intense colours being formed with p-hydroxybenzaldehyde or anisaldehyde. 

The Bucherer carbazole synthesis " involves the treatment of a naphthyl alcohol (1 or 4) or a naphthyl amine (2 or 5) with a phenylhydrazine 3 in the presence of aqueous sodium bisulfite to afford, after acidic work-up, either a benzo[a]carbazole 4 or benzo[c]carbazole 6. 

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. ... 

In the same fashion, the phenylhydrazone of 2-tetralone 43 was found to provide only one isomer, carbazole 44, when heated in dilute sulfuric acid. ... 

In 1896, Graebe and Ullman reported the formation of carbazole (5) by reacting 2-aminodiphenylamine (3) with nitrous acid, followed by the thermolysis of the benzotriazole 4 which resulted. ... 

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). 

Coupling reactions of indole-3-acetic acid derivatives have also p ovided convenient routes to indolo[2,3-a]carbazoles (Scheme 5). An iodine-p-omoted coupling... 

During studies on ditryptophan derivatives, an interesting acid-induced cy-cHzation has been discovered. The 10-membered ring 37 was thus subjected to acidic conditions to produce the indolocarbazole derivative 38 (Scheme 6). Interestingly, calculations performed on the precursor 37 indicated that the lowest energy conformation resembled that of the diastereomer of 38, which was never observed. An additional experiment furnished the parent system 1 on treatment of 38 with a catalytic amount of acid. A TFA-induced formation of an indolo[2,3-<3]carbazole was also observed from a related acyclic 2,2 -connected tryptophan dimer (99JOC8537). 

The parent indolo[2,3-fl]carbazole (1) has also been the subject of a study probing its reactivity toward oxidizing agents. One of the substrates involved, namely 85 (prepared from 1 and 2,5-dimethoxytetrahydrofuran in the presence of acid), was subjected to treatment with m-chloroperbenzoic acid, to give the dione 86 as the major product and a sensitive compound assigned the hydroxy structure 87. A cleaner reaction took place when 85 underwent oxidation with tert-butyl hydroperoxide assisted by VO(acac)2, to produce 86 exclusively in 86% yield. Likewise, A,N -dimethylindolo[2,3-fl]carbazole furnished the dione 88 on treatment with this combination of reagents (96J(X 413). 

A synthesis of an indolo[3,2-fl]carbazole (2) was reported in 1951—the first preparation of a compound belonging to this class (Scheme 13). This was accomplished commencing with cyclohexanone, via conversion to the bishydrazone 108, which underwent Fischer indolization in glacial acetic acid to furnish the octahy-dro derivative 109. After a final dehydrogenation step, the desired product 2 was obtained (51JCS809). 

An alternative route was later reported by Hall and Plant, who obtained 2 as well as the methyl derivative 110 in low yields, via the reaction of 5-aminotetrahydro-carbazoles with 2-chlorocyclohexanone, followed by dehydrogenation with palladium on charcoal of the intermediate octahydro derivatives 109 or 111 (53JCS116). The octahydro compounds 109 and 111 have also been reported as products from the reactions of suitable 1,3-phenylenediamines and 2-hydroxycyclohexanone in the presence of a catalytic amount of hydrochloric acid (53JCS4114). 

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... 

Indolo[3,2-fl]pyrrolo[3,4-c]carbazoles 120 have been obtained in one step from indole and the corresponding maleimides in acetic acid, with coformation of the Michael adducts 121 (Scheme 15). This reactitai required careful temperature control in order to obtain the desired product ratios. An alternative independent synthesis of compounds 120 could also be accompKshed from 2,3 -biindolyl (115) andsuitable maleimides in hot acetic acid (99T2363). The system 120 where R = H has also been reported as a minor product during studies toward a synthesis of the alkaloid arcyriaflavin A (95TL2689). 

In an investigation into the synthetic utility of the oxyindole 122, a wide variety of benzo- and heterocyclo-fused indexes and carbazoles was prepared, e.g., the indolo[3,2-a]carbazole 123 (Scheme 16). Thus, when 122 was reacted with indo-lylacetonitrile 124 in the presence of a base, followed by heating with phosphoric acid, the indolocarbazole 123 could be isolated in good yield (99T11563). 

The trifluoromethyl derivative 146 has been obtained as a minor product from the reaction of (l-methyhndol-3-yl)methanol with trifluoroacetic acid anhydride (TFAA), the major product (22% yield) being 6-trifluoromethylindolo[3,2-()]-carbazole [98LTC(B)841]. Several substituted indolo[2,3-()]carbazoles have also been encountered during studies on the reaction of 4,6-dimethoxyindole with... 

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). 

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