Alkylation methylene transfer

Dialkyl sulphides are converted into trialkylsulphonium salts by treatment with an alkyl halide (the bromide or iodide is usually the reactant of choice). An important example of this group is trimethylsulphonium iodide, which is used as a methylene transfer reagent by virtue of its being converted in the presence of base into a sulphur ylide, which is a nucleophilic carbene equivalent. 

Cyclopropanation of 1 -alkenes.1 /-Butylsulfonylmethyllithium, generated in situ from this sulfone with methyllithium, serves as a methylene transfer reagent under catalysis with Ni(acac)2. Terminal alkenes and cyclic 1,2-disubstituted alkenes are cyclopropanated in 70-95% yield, but open-chain 1,2-disubstituted alkenes do not react with this reagent. Other alkyl methyl sulfones are much less effective for this purpose. 

Alkylations, Methylene chloride can be used for alkylation of alcohols and phenols at 20 in the presence of solid, pulverized KOH and a phase-transfer catalyst. Aliquat 336 is more effective than benzyltriethylammonium chloride. ... 

Those reactions of coenzyme A in which the a-methylene group of acetyl-CoA is added to an acceptor molecule may also be considered a type of alkyl group transfer. Although this position is activated by being in a CoA ester, the ester group itself is not primarily involved in the new carbon-carbon bond formation. 

The terminal R groups can be aromatic or aliphatic. Typically, they are derivatives of monohydric phenoHc compounds including phenol and alkylated phenols, eg, /-butylphenol. In iaterfacial polymerization, bisphenol A and a monofunctional terminator are dissolved in aqueous caustic. Methylene chloride containing a phase-transfer catalyst is added. The two-phase system is stirred and phosgene is added. The bisphenol A salt reacts with the phosgene at the interface of the two solutions and the polymer "grows" into the methylene chloride. The sodium chloride by-product enters the aqueous phase. Chain length is controlled by the amount of monohydric terminator. The methylene chloride—polymer solution is separated from the aqueous brine-laden by-products. The facile separation of a pure polymer solution is the key to the interfacial process. The methylene chloride solvent is removed, and the polymer is isolated in the form of pellets, powder, or slurries. 

A similar reaction is the methylenation of 3,4-dihydroxybenzaldehyde in the presence of a phase-transfer catalyst on a benign calcium carbonate surface [26]. Presumably, bonding of the vicinal hydroxyl groups is low thereby enhancing the reaction with the alkylating agent under the action of solvent-free microwave irradiation (Eq. 15). 

The active enzyme abstracts a hydrogen atom stereospecifically from the intervening methylene group of a PUFA in a rate-limiting step, with the iron being reduced to Fe(II). The enzyme-alkyl radical complex is then oxidized by molecular oxygen to an enzyme-peroxy radical complex under aerobic conditions, before the electron is transferred from the ferrous atom to the peroxy group. Protonation and dissociation from... 

A./V-Dialkylhydroxylamines and oximes are readily alkylated to produce O-alkyl ethers [34-36] and oximes also react rapidly with dichloromethane to form the methylene dioximes [36-38]. O-Benzylhydroxylamine can be prepared on a large scale by alkylation of A-hydroxyphthalimidc under phase-transfer catalytic conditions and subsequent solvolysis of the imide system [39]. 

Whereas alkylation of activated methylene systems by classical methods produces a mixture of mono- and dialkylated products, with the latter frequently predominating, phase-transfer catalytic procedures permit better control and it is possible to obtain only the monoalkylated derivatives. Extended reaction times or more vigorous conditions with an excess of the alkylating agent lead to dialkylated products or, with dihaloalkanes, carbocyclic compounds as the technique mimics dilute concentration conditions, e.g. the resonance stabilized cyclopentadienyl anion, generated under solidiliquid two-phase conditions, or under liquiddiquid conditions, reacts with 1,2-dihaloethanes to form spiro[2,4]hepta-4,6-diene (70-85%) [1-3]. Reaction with dichloromethane produces bis(cyclopenta-2,4-dien-l-yl)methane (60%) [4],... 

The low acidity of methylene groups, which are activated by only one electron-withdrawing mesomeric substituent, generally results in a lower reactivity under phase-transfer catalytic conditions. Monoalkylation normally occurs, sometimes to the complete exclusion of dialkylation, and further alkylation is generally only... 

Methylenesulphones are more acidic than the simple esters, ketones and cyano compounds and are more reactive with haloalkanes [e.g. 48-57] to yield precursors for the synthesis of aldehydes [53], ketones [53], esters [54] and 1,4-diketones [55] (Scheme 6.4). The early extractive alkylation methods have been superseded by solidtliquid phase-transfer catalytic methods [e.g. 58] and, combined with microwave irradiation, the reaction times are reduced dramatically [59]. The reactions appear to be somewhat sensitive to steric hindrance, as the methylenesulphones tend to be unreactive towards secondary haloalkanes and it has been reported that iodomethylsulphones cannot be dialkylated [49], although mono- and di-chloromethylsulphones are alkylated with no difficulty [48, 60] and methylenesulphones react with dihaloalkanes to yield cycloalkyl sulphones (Table 6.5 and 6.6). When the ratio of dihaloalkane to methylene sulphone is greater than 0.5 1, open chain systems are produced [48, 49]. Vinyl sulphones are obtained from the base-catalysed elimination of the halogen acid from the products of the alkylation of halomethylenesulphones [48]. 

The reactivity of phenylacetic esters with electron-deficient alkenes is generally fairly poor, even under phase-transfer catalytic conditions. The reaction with cinnamic esters is often accompanied by hydrolysis and the yield of the adduct with chalcone is generally <60% [10]. The activity of the methylene group towards alkylation has been enhanced by the initial complexation of the phenyl ring with chromium tricarbonyl (see Section 6.2), but this procedure has not been applied to the Michael reaction. 

Deprotonation provides the necessary electron push to kick out the electron pair joining C(6) with the nitrobenzene oxygen. If, however, N(l) is alkylated (as with the nucleosides and nucleotides), OH catalysis is much less efficient since it now proceeds by deprotonation from N(3) (with the uracils) or from the amino group at C(4) (with the cytosines). In these cases the area of deprotonation is separated from the reaction site by a (hydroxy)methylene group which means that the increase in electron density that results from deprotonation at N(3) is transferable to the reaction site only through the carbon skeleton (inductive effect), which is of course inefficient as compared to the electron-pair donation from N(l) (mesomeric effect) [26]. Reaction 15 is a 1 1 model for the catalytic effect of OH on the heterolysis of peroxyl radicals from pyrimidine-6-yl radicals (see Sect. 2.4). 

The carbon-bond-forming reactions based on hydrogen transfer catalyzed by Cp Ir complex have been extended to the alkylation of active methylene compounds. Grigg et al. reported the alkylation of arylacetonitriles catalyzed by the... 

In the initial step of the polymerization, a cyclic oxonium ion is formed by transfer of an alkyl group from the initiator to the cyclic ether. Propagation occurs by SN2 attack of a monomer molecule at a ring a-methylene position of the cyclic tertiary oxonium ion, followed by opening of the oxonium ring and formation of a new cyclic oxonium ion. 

Volatile alkyl halogenides such as methyl iodide, methylene chloride etc., react quantitatively with the solid methylamine salt of 5-benzylidene- (39a) [32] and 5,5-diphenylthiohydantoin (37) to form the anticonvulsive solids 225 and 226 in quantitative yield [28] (Scheme 30). Unlike the solution reaction, only the S-alkylation occurs under gas-solid conditions. Furthermore, various dialkylamidodithiolate salts 228 react readily with dichloromethane at 80 °C. The salts with the quaternary cations react at room temperature and it is also possible to catalyze the reaction of the sodium salt by admixture of 10% of the corresponding phase transfer bromides [28]. These reactions have been tuned for removal of dichloromethane from loaded air streams [28]. 

Numerous methods to prepare individual classes of aliphatic diazo compounds have been extensively developed. The major strategies for their synthesis involve the alkaline cleavage of N-alkyl-N-nitroso-ureas, -carboxamides and -sulfonamides, dehydrogenation of hydrazones, as well as diazo group transfer from sulfonyl and related azides to active methylene compounds, and electrophilic diazoalkane substitution reactions. These synthetic methods have been comprehensively reviewed (15,16). Useful information on the preparation of selected diazo compounds can be found elsewhere (6,17). 

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