Methane alkylation with

The reaction of methane tricarboxylate with indoline 342 gave the tricyclic derivative 361 which can be transformed to the amide derivatives 362 (97JHC969). Alkylation of the iV-benzyl indoline 360 with pentafluor-oacetone gave 363 which upon debenzylation and subsequent acylation with diketene followed by cyclization gave 364. Other haloacetones were used to prepare different halogenated derivatives (79BEP872311) (Scheme 63). 

Alkylation of the metallated bis(triphenylphosphinyl)methane (6) with benzyl or methyl chlorides occurred on phosphorus to give the ylides (7). That from benzyl chloride reacted with chlorodiphenylphosphine to give the stable ylide (8). 

A further possibility for side-chain alkylation of toluene is oxidative methylation with methane. Catalysts with occluded alkali metal oxides, prepared by impregnating zeolites with alkali metal hydroxides followed by calcination, usually exhibit better performance.441 Further enhancement was achieved by impregnating ion-exchanged zeolites 442 Significant improvements in stability and the yields of Cg hydrocarbons were also observed when NaX was impregnated with 13% MgO which was found to increase the amounts of active sites.443... 

Endonuclease II of E. coli was first recognized by Friedberg and Goldthwait as an activity in extracts of E. coli mutants lacking endonuclease I, that specifically attacked double-stranded DNA alkylated with the monofunctional alkylating agent methyl methane sulfonate (56). It was subsequently found that the partially purified enzyme could in fact... 

Etbylamine can be alkylated with iodo methane in the presence of a strong base. The strong base is needed ... 

Alkylation of 3-aryl-l,2,3,4-thiatriazolium-5-olates 38 with triethyloxonium tetrafluoroborate leads to 5-ethoxy substituted thiatriazolium salts 37 (R = Ar) <1975T1783>. In the same manner, the aminides 129 react with iodo-methane to afford the thiatriazolium salts 131 with disubstitution at the exocyclic nitrogen (Scheme 31) <1998JMT27>. Also the mesoionic compounds 127 are readily alkylated with different alkylating agents <1997MRC124>. 

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). 

Friedel-Crafts Alkylations with Multiply Chlorinated Methanes... 

Alkanes can react with halogens (F2, CI2, Br2,12) to form alkyl halides. For example, methane reacts with chlorine (CI2) to form chloromethane (methyl chloride), dichloromethane (methylene chloride), trichloromethane (chloroform), and tetra-chloromethane (carbon tetrachloride). 

The sodium or potassium alkoxide prepared from primary and secondary alcohols and sodium hydride or potassium hydride in THF reacts with 2-(trimethyl-silyi)ethoxymethyl chloride (SEMCl, bp 57-59 PC/1 kPa, HAZARD carcinogenic) to give the SEM ethers in good yield [Scheme 4.304]481 Alternatively, the alcohol can be alkylated with SEMC1 in the presence of f-PrjNEt in dichloro-methane at 4013 C [Scheme 4.305].257,525,555 Conversion of the SEMCl to the corresponding iodide in situ using tetrabutylammonium iodide accelerates the reaction ... 

In on attempt to generate primary (trivalent) cations and to simulate the ethylene-methane alkylation, ethyl chloride was reacted with methane (eq. 3) under alkylation reaction conditions (28). When no propane or propylene product was observed, the energetically more favorable reaction of methyl chloride with ethane was carried out (eq. 3a). These two reactions proceeded without any involvement of the alkane and provide evidence that the ethylene-methane alkylation proceeds through a more stabilized species such as a pentacoordinoted carbonium ion. The behavior of these alkyl chlorides will be discussed separately after the alkylation chemistry. 

Sublimation of tetraneopentyl zirconium onto the surface of silica dehydroxylated at 500 °C results in the electrolytic cleavage of one Zr-C bond by a surface proton, with the formation of the tris neopentyl zirconium [Si]-0-Zr(CH2CMc3)3 grafted species. Reaction of this supported Zr alkyl with hydrogen at 150°C leads to the formation of a zirconium hydride. Interestingly, this reaction does not yield neopentane, but rather the formation of methane and ethane are observed. These products are in fact the result of the hydrogenolysis of evolved neopentane catalyzed by the silica-supported zirconium hydride. ... 

The alkoxydi(sulfonyl)methane shown in Scheme 128 (entry b) has been used as a useful carbonyl 1,1-dipole synthon ( C°-0). Its alkylation with alkyl halides is best achieved using CS2CO3 in DMF at 50 °C, and its palladium-catalyzed allylation requires the use of phase-transfer conditions (Scheme 128, entry b). The unmasking of the carbonyl group was then achieved by reacting the resulting disulfone with boron trichloride (-78 C, CH2CI2) followed by the addition of alcohols or amines to provide esters or amides respectively (Scheme 128, entry b). ... 

Recently Yoshida et al. have employed silyl-stabilized a-alkoxy organolithium reagents for the synthesis of a variety of carbonyl compounds. Methoxy(trimethylsilyl)methane and methoxybis(trimethyl-silyl)methane, when deprotonated with Bu Li and Bu"Li respectively, give anions which can be alkylated with a variety of electrophiles. Electrolysis of a solution of the alkylated product in methanol yields, by virtue of the reduced oxidation potential of ethers a-substituted with silicon, either the dimethyl acetal or in the latter case the orthoester. The mildness of the electrolytic process recommends the method for the preparation of a variety of carbonyl compounds. 

Ipatieff and coworkers carried out the first alkylation with alkenes and branched and normal chain alkanes (except methane and ethane) in the presence of AlCb as the catalyst. The sulfuric acid catalyzed alkylation reaction of arenes and isoalkanes, developed in 1938, is a still widely used industrial process to produce alkylates with high octane numbers. For synthetic applications, however, Friedel-Crafts-type alkylations of alkenes and alkanes have limited value since they tend to give mixtures of products, including oligomers of alkenes. ... 

To be able to determine theophylline in the ng range, Arbin and Edlund improved their method by derivatizing theophylline and the internal standard theobromine using penta-fluorobenzyl bromide, in connection with an electron capture detector. To 100 ul samples of plasma containing 50-1000 ng theophylline, 100 yl of a solution of the internal standard were added. The extraction was performed by column extraction (cellulose) using dichloro-methane as solvent. After back extraction into an alkaline aqueous phase (NaOH), theophylline and theobromine were alkylated with pentafluorobenzyl bromide by an extractive alkylation technique. The derivatives were extracted with cyclohexane and, after concentration to 3 ml, 2 yl were injected for the gas chromatographic assay. Standard deviation of the method was 2.5 % at a concentration level of 200 ng per sample, and 8 % at 20 ng per sample. The sample amounts were 100 yl plasma and 250 mg rat brain tissue, and the sensitivity limit... 

The authors speculate that the stereochemical divergence may be related to the ability of the electrophile to coordinate with the lithium, coupled with the presence or absence of a low-lying LUMO. Curiously, protonation by methanol proceeds with retention whereas protonation with either acetic acid or triphenyl methane proceeds with inversion. The authors speculate that, in acetic acid, protonation of the TMEDA nitrogen and internal return (c/. Schemes 3.2 and 3.24) may occur instead of direct protonation [184]. Presumably, direct protonation is the only mechanistic course with weak acids such as methanol and triphenylmethane and steric effects dictate inversion for the latter. Hoppe also noted that the enantiomeric purity of the products also depended on the solvent. In THF, the products were nearly racemic, and the enantiomeric purity of several of the other alkylation products was variable in solvents such as ether and pentane. This variability is due, at least in part, to the degree of covalency of the C-Li bond. In donor solvents such as THF, racemization is more facile. 

---