Electrophilic methylation

We can see from these data that benzyl radical significantly easier adds to electrophilic methyl acrylate and acrylonitrile than to relatively nucleophilic hex-1-ene. This is one of the arguments for a nucleophilic character of benzyl radical. The polar factors affect essentially kinetic parameters of the processes, as judged from the ratios / KadC4H9 = g3 and K dCOOCHa / k C4H9 = 41. The... 

Lysine is the most common site for N-methylation, but methylation can also occur on arginine, histidine, glutamine, and asparagine. The enzymes responsible for N-methylation are known as N-methyltransferases aided with SAM as a cosubstrate. All forms of methylation share the same mechanism the nucleophilic amino acid side chain attacks the electrophilic methyl group of SAM and releases S-adenosylhomocysteine (SAH) (Scheme 7). 

On co-adsorbing phenol and methanol, the protonation of methanol occurs on the active acid sites as the labile protons released from the phenol reacted with methanol. Thus protonated methanol became electrophilic methyl species, which undergo electrophilic substitution. The ortho position of phenol, which is close to the catalyst surface, has eventually become the substitution reaction center to form the ortho methylated products (Figure 3). This mechanism was also supported by the competitive adsorption of reactants with acidity probe pyridine [79]. A sequential adsorption of phenol and pyridine has shown the formation of phenolate anion and pyridinium ion that indicated the protonation of pyridine. 

Another experiment in which sequential adsorption of phenol and pyridine then followed by methanol shows formation of pyridinium ion and phenolate anion whereas no traces of methanol or electrophilic methyl species or formation of methylated products were identified on the catalysts surface. This result was supposedly confirmed from another experiment in which anisole and methanol were co-adsorbed on the catalyst. The spectra were referred to the molecular species of methanol and anisole without any significant interaction among them and above 200°C they simply desorbed from the catalyst. 

Needle like nanoparticles of Mg-Al mixed spinel catalysts synthesized under hydrothermal conditions were used for the synthesis of 1-methylimidazole by the gas phase imidazole methylation with methanol performed at atmospheric pressure [113]. High yield and selectivity to desired product were obtained at a temperature range between 320 and 350°C. It was proposed that one of the nitrogen atoms participates in the bonding of the imidazole with the basic site of the catalyst, and the second nitrogen atom is accessible for the reaction with electrophilic methyl species formed from methanol on acid site of the catalysts. 

Plant sterols such as stigmasterol typically contain an extra ethyl group when compared with cholesterol. Now this is not introduced by an electrophilic ethylation process instead, two successive electrophilic methylation processes occur, both involving SAM as methyl donor. Indeed, it is a methylene derivative like that just seen in ergosterol formation that can act as the alkene for further electrophilic alkylation. After proton loss, the product has a side-chain with an ethylidene substituent the side-chains of the common plant sterols stigmasterol and sitosterol are then related by repeats of the reduction and dehydrogenation processes already seen in ergosterol formation. 

The iodide content of the catalyst formulation is the key to avoiding these problems of competing reactions and achieving maximum acetic acid selectivity. The addition of iodide ensures that any initially formed methanol (7) is rapidly (H) converted to the more electrophilic methyl iodide. However, further increases in the quantities of iodide beyond that needed for methanol conversion to methyl iodide may lead to a portion, or all, of the catalytic-ally active cobalt carbonyl reverting to catalytically inactive cobalt iodide species - e.g. the [Col4] anion identified in this work, or possibly the cationic [Co(MeOH) (CO) I species (9). 

Ghyczy M, Boros M (2001) Electrophilic methyl groups present in the diet ameliorate pathological states induced by reductive and oxidative stress a hypothesis. Br J Nutr 85 409-414 Gilbert BC, Silvester S (1997) EPR studies of the role of copper in bio-organic free radical reactions. Copper-catalyzed oxidations of thiols with peroxides, especially those involving glutathione. Nukleonika 42 307-322... 

When no ft hydrogen is available, however, compounds as those shown in Scheme 4.5 can be useful electrophiles in nucleophilic substitutions. Thus, Me3S+OH [28], Me3S=0+X [29, 30], Me3Se+OH [31], (MeO)2CO [32-34], or MeN02 [35] can all be used as electrophilic methylating reagents. 

Ghyczy, M. and Boros, M. Electrophilic methyl groups present in the diet ameliorate pathological states induced by reductive and oxidative stress a hypothesis. Hr. J. Nutr. 2001 85 409-14. 

It can be seen from Tables 11 and 12 that the reactivity of the a-substituted acrylonitriles and acrylates toward the polystyryl radical (l/r2) increases slightly with the bulkiness of the substituent if the electronic factors are kept constant (COOMe < COOEt or COO/Bu), and also increases regularly with the electro-philicity of the olefin in each series. A noticeable exception to the last rule is methyl a-ethylthioacrylate H2C=C(SEt)COOMe, whose l/r2 value of >100 [70] is higher than the values for the very electrophilic methyl a-cyanoacry-late H2C = C(CN)COOMe (l/r2 = 100) [101] and diethyl methylenemalonate H2C = C(COOEt)2 (l/r2 = 33) [96,98]. As mentioned above its equivalent in the... 

The only doubtful case is the secondaiy alkyl derivative, which can react by either mechanism, though it is not very good at either. The first question you should ask when faced with a new nucleophilic substitution is Is the carbon electrophile methyl, primary, secondaiy, or tertiary This will start you off on the right foot, which is why we introduced these important structural terms in Chapter 2. 

Having successfully developed a workable route to dodecamethyl- and decamethyl-p-carboranes by triflate-mediated electrophilic methylation of all available BH vertices, it became important to attempt the similar methylation of 1,2- and 1,7-C2Bi0Hi2 and at the... 

In this case, however, homologation is quite different to the electrophilic methylation of olefin discussed above. Instead it comprises alkylation of a methylide group by alkyl cation. If this alternative homologation mechanism is operative it may not be confined to initial olefin formation but may compete with the presently accepted homologation mechanism in forming olefins more generally. 

A self-consistent explanation of all the chemistry can be developed on the basis of Rri6nsted acidity of the zeolite, proton transfer and electrophilic methylation reactions, and the well known rearrangement, oligomerization and cracking reactions of carbenium ions. 

The metabolism of DMN by a-hydroxylation is outlined in Fig. 12. a-Hydroxylation yields the unstable intermediate, a-hydroxydimethylnitro-samine, which spontaneously decomposes to monomethylnitrosamine and formaldehyde. The former gives rise to methanol via an electrophilic methylating agent. A deuterium isotope effect of 1.8-2.8 has been determined for the N-demethylation of DMN-t/g, indicating that the initial hydroxylation is rate-limiting (91, 276). The rates of formation of formaldehyde and methanol in rat hepatic 10,000 g supernatant have been measured the rates accounted for the metabolic fates of both methyl groups of DMN (280). Equimolar amounts of formaldehyde and methanol were also formed in the solvolysis of... 

Arginine methylation is catalysed by protein arginine methyltransferases (PRMTs, EC number 2.1.1.125), and thus far eight human PRMTs have been identified, with several more putative enzymes predicted. Two subclasses of PRMTs exist Class I PRMTs catalyse asymmetric dimethylation, while Class II PRMTs catalyse symmetric dimethylation of arginine. All three methyl-transferase subfamilies (SET-domain KMTs, DOTIL and PRMTs) utilise S-adenosylmethionine as an electrophilic methyl source. 

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