Halomethylation carbonyl compounds

Another indole synthesis which corresponds to the Ic pattern is the reaction of anilines with a-halomethyl carbonyl compounds. The reactions of IV-alkylanilines with y-bromo or y-chloro-acetoacetate esters gives indoles in fair to good yields. This method can be applied to indole-3-acetate esters and amides and can incorporate branching in the acetate side-chain (Equation (25)) <62BSF1056, 64BSF1939). 

The combination of 2-halomethyl-3-halo-l-propene with carbonyl compounds mediated by indium in water generated / /.v-allylation... 

Halides are extremely versatile intermediates. One of their more valuable and interesting transformations is their oxidation to carbonyl compounds, thus providing straightforward routes to relatively inaccessible compounds such as 1,2-diketones and heterocyclic aldehydes. As will be seen below, there are many, often complementary, synthetic methods for the oxidation of organic halides. The oxidation of halomethyl compounds has been reviewed recently. ... 

Halomethyl aryl sulfones. M kosza et al. report that chloro- and bromo-methyl aryl sulfones are converted into carbanions in 50% aqueous sodium hydroxide in the presence of this quaternary ammonium salt. The carbanions are readily alkylated and condense with carbonyl compounds to form oxiranes. Examples ... 

The use of halomethyl vinylsilanes would appear to offer significant promise. As allylic halides, they should be sufficiently reactive to permit regiospecific alkylation as vinylsilanes, they can be converted, via a,/3-epoxysilanes, into carbonyl compounds. The conditions for this last transformation, with simple a, 8-epoxysilanes, are rather vigorous, requiring hot methanol/ sulfuric acid. 

What about the applicability of organolithium compounds of type 29 with heavy organoelement groups in organic synthesis At present we can realize three modes of use (Scheme 39). The antimony compound is suitable as a reagent for nucleophilic halomethylation Nucleophilic lithiomethylation and carbonyl olefination, two other modes of application, are the objects of Sects. 4.4,4.5, and Chap. 5. 

Halomethyl compounds are subdivided into monohalomethyls, which are alkylating agents, and polyhalomethyls, which must be metabolized to an ultimate species. Reductive dechlorination of carbon tetrachloride 353) to chloroform by rabbit liver microsomes parallels the concentration of cytochrome P-450 in the microsomes but requires anaerobic conditions and NADPH. The identification of hexachloroethane after incubation of NADPH-reduced microsomes with carbon tetrachloride is indicative of homolytic formation of the free radicals of chlorine and trichloromethyl and supports the hypothesis that such species initiate an autocatalytic peroxidation of lipid membranes that results in the observed hepatotoxicity. A similar scheme for radical formation and lipid destruction has been described by Reynolds and Moslen for halothane. In contrast to the reductive dechlorination of carbon tetrachloride, the metabolism of chloroform to carbon dioxide in vitro requires oxygen and produces carbonyl chloride (phosgene) as an intermediate. That this also... 

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