Carbazoles acylation

The aromatic amides have attracted considerable interest from the photochemical point of view. However, anilides are less prone to photochemical rearrangements than the analogous phenyl esters. For this reason, the side reactions involving other parts of the molecule may compete favorably with PFR. Shizuka started the study of anilides in the 1960, and thereafter a number of papers have appeared dealing with the PFR of A -acyl anilines, carbazoles, indoles, and so forth. 

In the acetylation of carbazole using dimethylacetamide-phosgene in methylene chloride, attack was shown to occur mainly at nitrogen (93 7, N C-3) trifluoroacetylation proceeded exclusively at nitrogen. Carbazole was more reactive in this sense than indole and much more reactive than pyrrole, a result paralleling their respective basicities at nitrogen (see Section II,A,3). N-Acylation under these conditions is thought to involve... 

The preformation of carbazol-9-ylpotassium (sodium) has been much less used for the introduction of acyl groups onto nitrogen examples are the formation of 9-methoxy- and 9-ethoxy-carbonylcarbazoles, the dithio-carbamate salt 51, and the malonate 52 by reaction with the alkoxy-chloroformates, carbon disulhde, and malonic acid half-acid chloride, respectively. 

For 9-acylations, however, it is usually unnecessary to preform an anion. Direct electrophilic attack at carbazole nitrogen can occur (see Section II,A,4) followed by loss of the N-proton to produce iV-acylcarbazoles conveniently. 

The general picture emerging is that acid chlorides are sufficiently electrophilic to N-acylate carbazole directly but that acid anhydrides require a Lewis acid or protonic acid catalyst. Direct and efficient N-trifluoroacetyla-tion with trifluoroacetic anhydride nicely illustrates the balance, this more reactive anhydride requiring no catalyst. ... 

The dichloroacetal 53 N-acylated carbazole in the presence of stannic chloride producing 54, and trichloromethylthiomethane led to the thio-carbamate 55 on reaction catalyzed by zinc chloride. Carbazole reacts... 

Acyl groups are easily hydrolytically removed from carbazole nitrogen, done best with alkali, " or by exposure to alumina or under more vigorous conditions with aqueous acid. ... 

Lithium aluminium hydride treatment of 9-acylcarba2oles also regenerates the carbazole. At low temperature, reduction of the acyl residue proceeds only as far as the aldehyde oxidation level, and this provides a means for the conversion of acid to aldehyde via the 9-acylcarbazole. This process has been described for the preparation of benzaldehyde, cin-namaldehyde, and various a-amino aldehydes. Reduction of 9-ethoxy-carbonylcarbazole gave 9-hydroxymethylcarbazole. Mechanistically... 

In parallel with acylation (see Section II,D,3) nitration of 9-acetyl-carbazole, with silver nitrate-aluminium chloride, leads to the introduction of the electrophile at C-2, thus providing 2-nitrocarbazole efficiently after hydrolysis of the N-substituent. ° An early report that 9-tosylcarbazole is nitrated at C-1 could not be repeated. ... 

Normal acylation of carbazole amines and diamines, without reaction at the ring nitrogen, has been reported. Such amides can be easily... 

Indolo[3,2-3]carbazoles bearing a carbonyl substituent at the 6-position have been synthesized directly by an intramolecular cyclization approach from dichloroacetyl substituted precursors <2004EJO2593>. However, due to a facile decarbonylation under the reaction conditions it was found to be more expedient to employ esters, such as 165, produced by acylation with oxalyl chloride (Equation (79) Table 4). 

An interesting one-pot, five-component domino process using an intermolecular Diels-Alder reaction of furans with AT-phenylmaleimide as its final step has been used to construct the central core of indolo[2,3- ]carbazoles (Equation 86) <2002AGE4291>. Thus, aminooxazoles produced from an Ugi three-component reaction undergo acylation/intramolecular Diels-Alder/retro-Diels-Alder cycloreversion with pentafluorophenyl arylprop-2-ynoates to give furan derivatives. Subsequent Diels-Alder cycloaddition at elevated temperatures with A -phenylmaleimide produces carbazoles in good yields (Table 5). 

The acid-catalyzed ot7, o-acylation of /3-oxoalkyl derivatives of 7t-excess aromatic heterocycles known as the Dorofeenko-Dulenko-Krivun reaction affords condensed pyrylium derivatives which are convenient precursors of the corresponding pyridines <2001CHE1310>. By this approach (Scheme 14), carbazole 100 is converted into carba-zolo[3,2-f]pyrylium 101, a new ISrt-electron heteroaromatic system, and 101 is readily transformed into isomer 102 of 6-methylellipticine via an Sn(ANRORC) reaction using ammonia. The yields for these transformations were not reported. 

The acetylation of carbazole by acetic anhydride in the presence of boron trifluoride produces the 9-acetyl derivative. Further acetylation requires more vigorous conditions, using aluminum trichloride as a catalyst, and yields 2,9-diacetylcarbazole, which, upon base-catalyzed hydrolysis, produces 2-acetylcarbazole (80T3017). Acetylation of 1-phenyl-isoindole under mild conditions in the presence of pyridine yields l-acetyl-3-phenylisoin-dole, whereas the presence of an ester group at the 1-position deactivates the ring sufficiently to prevent acylation (81AHC(29)34l). 

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... 

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