Methane derivatives, halide

Of the synthetic reactions of the alkyl halides that with potassium cyanide, which enabled H. Kolbe to synthesise acetic acid from a methane derivative, has already been mentioned (cf. the preparations on pp. 137 and 254). Of the simpler syntheses that of Wiirtz may be mentioned here. Metallic sodium removes the halogen from two molecules and the two radicles combine. Thus, in the simplest case, ethane is formed from methyl bromide ... 

Chlorine or bromine reacts with alkanes in the presence of light (hv) or high temperatures to give alkyl halides. Usually, this method gives mixtures of halogenated compounds containing mono-, di-, tri- and tetra-halides. However, this reaction is an important reaction of alkanes as it is the only way to convert inert alkanes to reactive alkyl halides. The simplest example is the reaction of methane with CI2 to yield a mixture of chlorinated methane derivatives. 

Interestingly, reactive benzylic halides undergo the cross-couphng reaction in the presence of a catalytic amount of CuCN 2LiCl [49] leading to diphenyl-methane derivatives such as 343 (Scheme 4.77) [185]. 

Hydrogen cyanide (Table 15.1) is a colorless, flammable liquid or gas that boils at 25.7°C and freezes at minus 13.2°C. The gas rarely occurs in nature, is lighter than air, and diffuses rapidly. It is usually prepared commercially from ammonia and methane at elevated temperatures with a platinum catalyst. It is miscible with water and alcohol, but is only slightly soluble in ether. In water, HCN is a weak acid with the ratio of HCN to CN about 100 at pH 7.2, 10 at pH 8.2, and 1 at pH 9.2. HCN can dissociate into H+ and CN. Cyanide ion, or free cyanide ion, refers to the anion CN derived from hydrocyanic acid in solution, in equilibrium with simple or complexed cyanide molecules. Cyanide ions resemble halide ions in several ways and are sometimes referred to as pseudohalide ions. For example, silver cyanide is almost insoluble in water, as are silver halides. Cyanide ions also form stable complexes with many metals. 

The reaction of the carbanion derived from diethyl methylphosphonate with perhalogenated aromatics may result in substitution of halide to yield perhaloaryl(hetaryl)methylphosphonates, which can be converted into tris- or bis-(perhaloaryl)methanes. Displacement of fluoride ion has been reported in the reaction of dimethoxycarbene with l-fluoro-2,4-dinitrobenzene and with hexafluorobenzene. The hydrodehalogenation of halogenated aryl ketones may be facilitated using hydrogen over a Pt/C catalyst. " ... 

The preparation of acetic acid represents a special case. Olah and coworkers as well as Hogeveen and coworkers have demonstrated that CO can react with methane under superacidic conditions, giving the acetyl cation and by subsequent quenching acetic acid or its derivatives (see Section 7.2.3). Monosubstituted methanes, such as methyl alcohol (or dimethyl ether), can be carbonylated to acetic acid.115 Similarly, methyl halides undergo acid-catalyzed carbonylation.115,116 Whereas the acid-catalyzed reactions can be considered as analogs of the Koch reaction, an efficient Rh-catalyzed carbonylation of methyl alcohol in the presence of iodine (thus in situ forming methyl iodide) was developed by Monsanto and became the dominant industrial process (see Section 7.2.4). 

Most carbocations are too reactive to be directly observable in ordinary solvents, and until relatively recently evidence has been obtained indirectly, primarily through the study of reaction kinetics and trapping processes, experiments discussed in Sections 5.1, 5.2, and 5.4. Nevertheless, a few types of compounds have long been known to produce observable concentrations of positive ions relatively easily. The triarylmethyl derivatives were the first of this type to be investigated the halides ionize readily in non-nucleophilic solvents such as sulfur dioxide,70 and the alcohols yield solutions of the ions in concentrated sulfuric acid. Early observations by the freezing-point depression technique (see Section 3.2, p. 130) established that each mole of triphenyl carbinol yields 4 moles of ions in sulfuric acid, the reaction presumably being by way of Equation 5.14.71 Results in methane-sulfonic acid are similar.72... 

A new type of triaryl phosphine-functionalized imidazolium salt containing cations such as (6) has been prepared. Palladium complexes of (6) generated in situ have been used successfully in Heck-type reactions of aryl halides with acrylates and of 4-bromotoluene with styrene derivatives.34 The first Heck-type reaction of aryl halides with allenes has been reported. 1,3-Double arylations were observed with 3-substituted-l,2-allenyl sulfones, while 1-monoarylation was favoured with 3,3-disubstituted-l,2-allenyl sulfones.35 It has been shown that the a-arylation of methane-sulfonamides (7) may be achieved using palladium catalysis reaction proceeds through the sulfonamide enolates.36 It is also reported that palladium cross-coupling of alkynes with /V - (3 - i odophe n y I an i I i ncs) may lead to the formation of substituted carbazoles.37... 

Arylmethyl(homobenzyl)ethylsulfonium salts are appropriate substrates for Suzuki-type coupling reactions. In this reaction, performed on a polymer-bound sulfonium tetrafluoroborate, the benzyl fragment on the sulfur atom was transferred to the boronic acid residue. The sulfonium salt was prepared from an al-kylthiol resin by alkylation with a substituted benzyl halide to give thioether 98 and subsequent alkylation with triethyloxonium tetrafluoroborate. Reaction with a boronic acid derivative yielded diaryl methanes 99 [94] (Scheme 6.1.22). 

Similarly, reactions of C B(OMe)2 4 with Hg(OAc)2 afforded C(FIgOAc)4 125 a series of tetra-mercuro-methanes, C(HgX)4 (X = C1, Br, I, CN, SCN) has been obtained from reactions of C Hg(OAc) 4 with halides or pseudohalides.126 In turn, the acetoxy compounds derived from Hofmann s base , previously thought to contain a C2 unit, are now believed to be a polymeric oxonium ion formed by condensation of C Hg(OH) 4. Treatment of this compound with acetic or trifluoroacetic acids afforded C Hg(02R) 4 (R = Me, CF3). Extensive spectroscopic studies of these derivatives have been carried out. Further reactions with... 

In contrast to the condensation described above (Section II, A, 1) which proceeds vigorously because of continuous evolution of hydrogen halide, the methylmercapto compounds can be condensed with excess of methyl derivatives of N heterocycles in a slow and mild reaction16,17 Eq. (2) formulates this reaction for di-(2-quinolyl)-methane. 

Ben2 yl-type chlorides are converted to the corresponding cyanides much more rapidly (85-90%). Ring substituents include alkyl, halo, carbethoxy and nitro groups. The more reactive benzyl halides, particularly the p-methoxy derivatives, are subject to extensive alcoholysis when ethanol is employed as the solvent. The successful use of acetone, acetonitrile, and phenylacetonitrile as solvents has been described. Conversion by cuprous cyanide and pyridine has been successfully applied to benzyl chloride as well as to di-o-tolylchloro-methane. It is interesting to find that treatment of a-chloroethylbenzene, C,H,CH(C1)CH, with cuprous cyanide gives 1,3-diphenyI-l-butene,... 

Homologous Series of Alcohols.—As, hydroxyl substitution products of the hydrocarbons the alcohols form an homologous series analogous to that of the alkyl halides or halogen substitution products. Methyl and ethyl alcohol are thus the first two members of such a series derived from the methane or paraffin hydrocarbons. 

Synthesis of these simple type of thiol derivatives will be Just briefly discussed here because comprehensive reviews on thiols and their derivatives are available (2, 21 ). The methyl sulfide compounds are most readily obtained by methylation of the corresponding thiol. Nucleophilic substitutions with methane thlolate on alkyl halides and occasionally with aryl halides lead directly to the methyl sulfide product. The syntheses of methyl sulfide and sulfone metabolites of xenoblotlca are summarized In Table IX. 

A salt-type nomenclature is frequently used with alkyl halides in which the alkyl group s name precedes the name of the halide. In addition, halogen derivatives of methane have familiar non-systematic names. 

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