Halomethyl compounds

The Darzens reaction between aldehydes and ketones with activated halomethyl compounds is an effective route to oxiranes under phase-transfer catalytic conditions and the catalyst has a profound stereochemical control of the substituents (see Chapter 12). The reaction has been conducted in high yield under liquidtliquid and solidrliquid two-phase conditions with a range of halomethyl compounds [e.g. 25-30], Ketones tend to be much slower in their reaction and benzylic ketones undergo alkylation with chloroacetonitrile in preference to the Darzens reaction [25]. 

Aromatic and heteroaromatic aldehydes can alternatively be prepared from the corresponding methyl compound by subjecting the chloromethyl or bromomethyl derivative to the Sommelet reaction. This procedure involves an initial reaction between the halomethyl compound and hexamethylenetetramine (hexamine), and hydrolysing the resulting quaternary hexamine salt (4) with hot aqueous acetic acid. 

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. ... 

This is one of the oldest methods for the oxidation of halides,and has been used quite widely for the preparation of benzaldehydes and heteroaromatic aldehydes from the halomethyl compounds. Unacti-vat aliphatic halides give reduced yields. 

According to Angyal s recommendation,1 the optimal Sommelet reaction may be run without isolation of the hexaminium salt under such conditions 0.1 mole of halomethyl compound is heated under reflux for one or two hours with 30 g of hexamine in 90 mL of 50% acetic acid, or with 16.5 g of hexamine in 90 mL of 60% ethanol. 

Sulfone formed from (>-quiiiodimelhanc and SO2. Sulfone formed from bis(halomethyl) compound. Sulfone formed by annulaiion of a dihydrothiophene. Extrusion from suliine, Dcsiannylaiion. 

Reduction of the bis-halomethyl compound 43 results in ring closure and formation of benzo-fused 1,3-disilacy-clohexane derivatives (Scheme 17) <2003CHE813>. 

Stepwise synthesis Several diaza[3 ]- or triaza[3 ]cyclophanes were synthesized by the coupling reaction between N,N -di(aryl-sulfonylaminomethyl) compound dialkali salts and bis(halomethyl) compounds so far. 

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... 

Use of modified Swem-type conditions can give good yields ofO-methylthiomethyl (MTM) derivatives (190), which can be used to make various other derivatives such as the 3 -0-halomethyl compounds and, thence by Arbusov reactions, 3 -0-phosphonomethyl nucleosides.259 a similar 3 -0-MTM derivative was used to make the methylene analogue (191) of a dinucleoside phosphate, and a 5 -0-MTM ester of thymidine was used to link glucose and serine to 0-S of thymidine via methylene acetals.2 The spin-labelled spiroketal (192) derived from uridine has been prepared, and its e.s.r. properties studied.26l... 

The ammonolysis of bis(halomethyl) compounds yields polymers containing double bonds (18,27,49,57). An example is shown in Eq. (I-l 1). 

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