Carbazole, formation

Crossed-alkyne cyclotrimerizations between the diynes 580 and the monoalkynes 581 with a catalytic amount of RhClfPPhsls afforded substituted carbazoles 582. The high efficiency of the carbazole formation could be rationalized by the conformational restrictions present in the diynes 580 (561) (Scheme 5.27). 

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. 

In the absence of amine, the ketenimine-azirine singlet nitrene species can equilibrate and, eventually, the singlet nitrene can cychze to form carbazole. Berry and co-workers independently monitored the growth of carbazole ( max = 289.4 nm) by this process. In cyclohexane, some carbazole was formed this way with an observed rate constant of 2.2 x 10 at 300 K over a barrier of 11.5 kcal/mol. Tsao and co-workers recently used TRIR spectroscopy to show that ketenimine decay equals the rate of carbazole formation. 

In addition to products E and F, 16% (at 60% conversion) of 9-methyl-carbazole G has been isolated. Carbazole formation implies a loss of S02 from sulfone H and subsequent ring closure (Equation 30). 

Lehmann and Berry303 reported a flash photolysis study of the carbazole formation from 2-azidobiphenyl in the gas phase and in solution. The rate constant for cyclization of the nitrene was measured in solution at 300 K as 2.1B x 103 sec-1, and an activation enthalpy of 11.46 + 0.76 kcal/mol was derived. The rate in the gas phase at 75°C was unmeasurably fast (i.e., > 1.4 x 106 sec" ). It was concluded that a singlet nitrene was first formed, but that it was the triplet that underwent cyclization. 

However, Sundberg et al.304-305 demonstrated that two intermediates must be formed from the photolytically generated nitrene 240. These were supposed to be the immediate carbazole precursor 241, and the azirine 243 (Scheme 47) because part of the nitrenes could be trapped with diethylamine, giving 245. In conformity with the discussion in Sections VIII,A-C we have added the azacycloheptatetraene 244 in Scheme 47. Since the trapping reaction (to 245) was found to be a factor 102 faster than carbazole formation, but the formation of 242 could not be completely suppressed, 241 was assumed to be the nontrappable intermediate. It was also found304 that the deoxygenation of 2-nitrosobiphenyl proceeded in a similar manner, and that a similar product ratio (242 245) resulted. Therefore, a free nitrene appears to be involved in this reaction also. A more detailed flash-photolytic study305 excluded the triplet nitrene 240 as a principal carbazole precursor. The nature of the observable transient is still unclear, however. 

The formation of fluorene from 2-biphenylcarbene is completely analogous to the carbazole formation described above. Contrary to earlier beliefs, the facile gas-phase rearrangement of diphenylcarbene to fluorene (Scheme 51) is not a direct process (path a),208 Other carbocyclic analogs of this reaction have been reported,10,329 and it has allowed the preparation of a number of heterocyclic compounds in high yields as well as a deeper understanding of the carbene-nitrene rearrangement.210 232... 

In principle, the application of time-resolved techniques permits identification of intermediates by monitoring their progress to the stable products of reaction. In 1973, Lehman and Berry [25] reported the first application of time-resolved photochemical methods to the study of aryl azides. Using conventional flash photolysis, they irradiated 2-azidobiphenyl in cyclohexane solution. Time-resolved absorption spectroscopy revealed an intermediate assigned as the triplet nitrene primarily on the basis of the similarity of its spectrum to that measured by Reiser [18] in low-temperature experiments. Lehman [25] monitored the rate of carbazole formation and found it to occur by a kinetically first-order process with a lifetime of 460 /is at room temperature. These findings led them to conclude that photolysis of 2-azidobiphenyl at room temperature leads rapidly to the triplet nitrene, and that this species is the precursor to carbazole [25], However, this point of view clearly is at odds with Swenton s triplet sensitization experiments [23],... 

Swenton et al. [23] demonstrated that carbazole formation was a singlet state process in solution phase and that the major process on the triplet surface was the formation of azobiphenyl. 

In 1973, Lehman and Berry [25] studied the kinetics of this reaction by flash photolysis of the azide in cyclohexane. They were able to monitor the rate of formation of carbazole at 289.4 nm. They obtained the first-order rate constant to carbazole formation as a function of temperature (k bs(300K) = 2.18 x 103s Ea = 11.5kcal/mol). These workers were also able to observe the spectrum of a transient species produced by the flash. The rate of disappearance of the transient was comparable to the rate of formation of carbazole. Lehman and Berry [25] attributed the transient spectrum to triplet 2-biphenylnitrene and presented a mechanistic analysis consistent with this assignment. 

Sundberg et al. [21] reinvestigated this system by flash photolysis and were able to reproduce the earlier rate constant quoted in cyclohexane. They were able to demonstrate however that this reaction was subject to a considerable solvent effect. As previously mentioned, it was found that photolysis of 2-azido biphenyl in the presence of amines produced 3H-azepines in addition to carbazole. Although secondary amines reduced the yield of carbazole, some heterocycle is still formed even in neat amine. Thus there are two pathways for carbazole formation, one which can be quenched with amines and one pathway which cannot. 

Pyridines are observed in some of these reactions, and the substituent pattern is that expected from nitrene-carbene interconversion Small yields of azepine have been recorded in the photolysis of 158 i ). The bicyclic intermediate 44 [Eq. (64)] has been postulated frequently over the last twenty years. A wavelength dependence of the formation of azepines has been observed i ) the yield of azepine increases with the energy of the light and with the concentration of the trapping agent (diethylamine). At the same time, the yields of competitive processes of the nitrene (carbazole formation from 2-biphenylylnitrene p-cyanophenyl-hydrazine from p-cyanophenylnitrene) decrease. The rate of the azepine-forming... 

Indoles and Carbazoles. - Formation. 2-Arylindoles (132) are formed by intramolecular Wittig reaction of the phosphonium salts (131). The hydroxamic acids PhN(OH)COCH2COR (R = alkyl or aryl) cyclize in boiling toluene to mixtures of indoles (133) and 3-isoxazolones (134). Irradiation of a solution of o-iodoaniline and the potassium enolate of acetone affords 2-methylindole. The enamino-ketone (135) cyclizes photochemically to 1,2-dimethylindole (136) with elimination of acetaldehyde/ The styrene derivative (137), obtained by the action of Meerwein s acetal, Me2NCH(OMe)2, on o-nitrotoluene, yields 1-hydroxyindole on treatment with zinc/ Azidobenzocyclobutanes (138 R = Me, Ph, or CH2Ph) are converted into indoles (133) by the action of concentrated sulphuric acid/ ... 

The synthesis of a 2-hydroxybenzo[c]carbazole involves a Curtius reaction and carbazole formation by photolytic decomposition of an azide as shown in Scheme 20. Subsequent reaction with a propynol leads to an /-fused indole derivative of naphtho[l,2-b]pyran which absorbs further to the red than both 14 and the pyrrole derivatives in Scheme 19 <99WOP23071>. Absorption bands are shifted to the red when amino substituents are... 

Indoles and Carbazoles.- Formation, o-lodoaniline condenses with the potassium ————————— —... 

Carbazole formation from naphthols and aryl hydrazines promoted by sodium bisulfite. Another variant of the Fiseher indole synthesis. 

Cyclization of o-azidobiphenyls to carbazoles is one of the oldest and best studied arylnitrene reactions. Carbazole formation (67) has finally been shown " to involve cyclization of a singlet nitrene (68), generated by photolysis or thermolysis of 2-azidobiphenyl, settling a controversy of some standing. ... 

It has been considered that a coordinated nitrene may give the same reaction and work in our group has shown that this is indeed possible in at least one case [260] (see also Chapter 5). However, it should be also noted that we now know that most reactions of nitro- and nitroso compounds with a metal complex occur through an intermediate electron transfer to the organic compound vide supra). Thus the formation of the radical anion of o-nitro- and/or o-nitrosobiphenyl should be considered as probable during the reaction. The reactivity of such radicals is virtually unknown and it cannot be excluded that these species, and not a nitrene intermediate, are responsible for the carbazole formation. The validity of carbazole formation as an indication for nitrene intermediates has been questioned very early [261]. It was shown that other reactions (including oxidation of 2-amino-biphenyl) can afford carbazole. Thus the results of this test should be taken with caution. 

It was also demonstrated that, in the presence of DEA, photolysis of azide 65a leads to the formation of 3H-azepine 71a (Scheme 11.38), with a concomitant reduction in the yield of carbazole 66a. " The carbazole formation was measured at its absorption maximum (289.4 nm), and a rate constant was found to be 2.2 x 10 s at 300 K in cyclohexane. This value is about 5-6 orders of magnitude lower than the rate constants of singlet arylnitrenes rearrangement (Tables 11.1 and 11.2). Therefore, the following scheme (Scheme 11.38) could economically describe the early results. ... 

Recently the mechanism of carbazole formation upon photolysis of ort/to-biphenyl azide (65a), its deutero- (65a-d9) and dichloro (65b) derivatives was studied in detail... 

LFP of perdeuterated azide 65a-d9 at ambient temperature demonstrated a pronounced kinetic isotope effect on the kinetics of carbazole formation on the ns time scale (kn/ko = 3.4 0.2), which is consistent with the reaction being the isomerization of isocarbazole 72a into carbazole 66a by a 1,5-hydrogen shift. In addition methanol and water were found to accelerate the disappearance of the transient absorption of 72a produced upon LFP of 65a in pentane. A reasonable mechanism for this catalysis is shown in Scheme 11.39. 

Scheme 11.40 Mechanism of carbazole formation on a longer time scale...

Subsequently, Gaunt reported a Pd(II)-catalyzed intramolecular C-H bond amination strategy and its application to direct carbazole formations [21]. 

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