Halogenated carbazoles

Carbazoles, halogenation, 59, 266-8 Carbazole, lithiation, 56, 182 Carbazoles, 9-alkyl-, lithiation, 56, 182,... 

Strychnine can also be halogenated and sulphonated,i and among its high temperature decomposition products indole and carbazole have been recognised. ... 

In conclusion, the fantastically diverse chemistry of indole has been significantly enriched by palladium-catalyzed reactions. The accessibility of all of the possible halogenated indoles and several indolyl triflates has resulted in a wealth of synthetic applications as witnessed by the length of this chapter. In addition to the standard Pd-catalyzed reactions such as Negishi, Suzuki, Heck, Stille and Sonogashira, which have had great success in indole chemistry, oxidative coupling and cyclization are powerful routes to a variety of carbazoles, carbolines, indolocarbazoles, and other fused indoles. 

The chemistry of carbazoles was last reviewed in 1952 and 1954 following earlier accounts. More recently, Rodd s first edition coverage was updated and halogen derivatives of carbazoles were reviewed. Alkaloids... 

There are several examples of the 1,2-elimination of hydrogen chloride from 9-(2-chloroethyl)carbazoles, using potassium hydroxide in ethanol, generating the 9-vinylcarbazoles. 3-Dimethylamino-9-(2-hydroxyethyl) carbazole comparably lost water on base treatment. Dimethylamine displacement of halogen, then amine N-oxide formation and elimination was utilized to produce 9-alkenylcarbazoles with four, five, and six carbon atoms from the corresponding cu-haloalkyl carbazoles. ... 

A subsequent elimination of hydrogen halide prompted by the lability of halogen on the carbon attached to nitrogen, a second halogen addition, and a repetition of the cycle must account for the reported formation of 9-pentachloro- and 9-pentabromoethylcarbazoles on reaction with excess halogen in methanol and acetic acid, respectively. Addition of bromine to IV-vinylcarbazole in benzene as solvent was accompanied by 3,6-dibromi-nation in ethanol, 3,6-dibromo-9-(2-bromo-l-ethoxyethyl)carbazole was reportedly formed (cf. ref. 230). 

The acetoxy group of 9-(l-acetoxyethyl)carbazole is easily displaced with alcohols. Easy displacement of a similarly situated halogen can be achieved, as has been noted before (see Section II,C,2) thus methanol converts 9-(l-chloro-2-iodoethyl)carbazole to 9-(2-iodo-l-methoxyethyI) car-bazole. Elimination of acetic acid or ethanol by strongly heating 9-(l-acetoxyalkyl)- or 9-(l-ethoxyalkyl)carbazoles gives 9-vinylcarbazoles. In the absence of acid, ( )-alkenes are produced, but acid catalysis leads to a mixture of E and Z isomers. Acetyl chloride in pyridine also effects ethanol elimination. ... 

Most of the polymer modifications incorporating benzo-substituted pyrroles have been done with the dibenzo derivative, carbazole, primarily because of its well-known photocon-ductive properties. The modification reaction often involves a substitution reaction on some halogenated polymer. This substitution reaction can be quite facile. Poly(vinylbenzyl chloride), for example, reacts with the potassium salt of carbazole in DMF to yield the carbazole-functional polymer in 97% yield (76MI11110). 

Newly discovered halogenated carbazoles will be presented in a future volume. 

Compared to the number of halogenated pyrroles and indoles, the number of known halogenated carbazoles, carbolines, indolocarbazoles, and related compounds is much smaller <96MI1>, and the number of recently discovered examples of these types is fewer still. 

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. 

The halogenation of dibenzo derivatives of five- and six-membered heterocycles presents a rather clear orientation pattern. The preference for substitution ortho and para to atoms having available electron pairs [e.g., phenoxathiin (26) and carbazole] reflects the stabilization... 

Of the more than 4500 known naturally occurring organohalogen compounds, a large fraction are alkaloids [1,3]. Most of these halogenated pyrroles, indoles, carbazoles, carbolines, tyrosines, and others have a marine origin. The present chapter surveys the occurrence, structure, and biosynthesis of these fascinating natural products. However, given their sheer number, this review focuses mainly on recent examples. 

Chlorobenzene is employed in the synthesis of certain amino-containing vat dye intermediates. When reacted with phthalic anhydride, the product is 2-chloroanthraquinone, which, with ammonia, is converted readily into 2-aminoanthraquinone (61). Other routes include replacement of halogen by amino groups, with ammonia or ammonium salts of urea, and alkyl- and aryl amines to afford secondary amines. Modification of the amino group by alkylation, with dimethyl sulfate, alkyl halides or esters of toluenesul-fonic acids, is of synthetic value. Arylation of the amino groups is of importance only in the reaction between aminoanthraquinones and nitro- or chloroanthraquinones to yield dianthraquinonylamines, or anthrimides48. For example, the reaction between 62 and 63 yields 64, which can then be converted into carbazole 65, Cl Vat Brown R (Scheme 14). Amination of haloanthraquinones such as l-amino-4-bromoanthraquinone-2-sulfonic acid (bromamine acid) (66), prepared from 1-aminoanthraquinone, is of industrial use. 

Abbreviations used in text AA, arachidonic acid AhR, aryl hydrocarbon receptor Amt, AhR nuclear translocator BR, bilirubin BV, biliverdin CYP1A1, cytochrome P4501A1 DRE, dioxin responsive element FICZ, 6-formylindolo(3,2b)carbazole HAH, halogenated aromatic hydrocarbon I3C, indole 3-carbinol ICZ, indolo-(3,2,-b)-carbazole PAH, polycyclic aromatic hydrocarbon RAR, retinoic acid receptor TCDD, 2,3,7,8-tetrachlorodi benzo-/>-dioxin Trp, tryptophan UGT 01, UDP-glucuronosy 1 transferase 01... 

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