Methyl group substitution reactions

Kutney et al. ° have investigated the general reactivity of the various positions in the vindoline (205) nucleus, and have prepared several new derivatives. Electrophilic substitution occurs with particular facility at position 10, as expected Nb can be protected as the 3-lactam by oxidation with mercuric acetate, preferably on vindoline O-acetate. In contrast, dihydrovindoline derivatives are oxidised at position 5. Potassium permanganate was observed to attack both positions 3 and 5, with concomitant oxidation of the iVa-methyl group. Substitution reactions in ring C, particularly at C-17, depend critically on the existing substitution, and on the conformation of ring c. 

Toluene, an aLkylben2ene, has the chemistry typical of each example of this type of compound. However, the typical aromatic ring or alkene reactions are affected by the presence of the other group as a substituent. Except for hydrogenation and oxidation, the most important reactions involve either electrophilic substitution in the aromatic ring or free-radical substitution on the methyl group. Addition reactions to the double bonds of the ring and disproportionation of two toluene molecules to yield one molecule of benzene and one molecule of xylene also occur. 

Substitution Reactions on the Methyl Group. The reactions that give substitution on the methyl group are generally high temperature and free-radical reactions. Thus, chlorination at ca 100°C, or in the presence of ultraviolet light and other free-radical initiators, successively gives benzyl chloride, benzal chloride, and benzotrichloride. 

An example of geometric isomerism is provided by the dimethylpyrrolidinecarboxanilides (18). Only when the methyl groups substituted on the pyrrolidine ring are in the ois-conformation is electron transport inhibited and phytotoxicity produced. The trans-isomer neither inhibits the Hill reaction, nor is it phytotoxic. 

Substitution Reactions on the Methyl Group. The reactions that give substitution on the methyl group are generally high temperature... 

An experimental Acan be derived from the temperature dependence of the second-order rate constant, which yielded a value of 25.9 kcal/mol.59 Although it appears that this disagrees with the computed free energy of activation (16.6 kcal/ mol) for the reaction of H3N + CH3SH2 in water, the difference actually originates from the intrinsic reactivity of the two reactions. The additional methyl group substitutions both on the nucleophile and substrate raise the gas-phase barrier by 10 kcal/mol to a value of 10.5 kcal/mol at the HF/6-31G(d) level. Taking the methyl substitution effect into account, the computed solvation effect in fact is in accord with experiment,59 which is about 15 kcal/mol (25.9 — 10.5 kcal/mol). 

Piano-stool iron complexes bearing NHC have been obtained by substitution of a CO ligand from [(Cp)Fe(CO)2X] (56), as illustrated in Scheme 9. When X was a methyl group, the reaction, performed at room temperature, afforded... 

Methyl groups substituted on 1,2,4-triazines react with chlorine or phosphorus pentachlo-ride to give chloro-, dichloro- and trichloromethyl-l,2,4-triazines 1.189,290,291,298,300 The chlorine undergoes substitution by other nucleophiles, such as ethanol/sodium ethoxide to afford alkoxymethyl derivatives.390,300 However, reaction of the 5-trichloromethyl group with methanol/sodium methoxide yields the 5-metlioxy compound 2 (vide supra Table ll).300... 

A mixture of formaldehyde with ammonia or a primary or secondary amine can be used to replace mobile hydrogen by an aminomethyl or (substituted amino)methyl group. This reaction, which was systematically explored by Mannich,698 can be formulated as ... 

Gadamer and von Bruchhausen (87), who showed that corycavine contains CHa more than protopine, regarded it as a homolog of the latter, and demonstrated that it showed the reaction characteristic of the protopine alkaloids (15). Reduction with sodium amalgam in acid solution yielded dihydrocorycavine, and this as well as the unreduced base on treatment with phosphoryl chloride yielded a quaternary chloride. These compounds are formulated as VII and XVIII, respectively, with a methyl group substituting one of the hydrogens. 

Figure 2.25 Methanol is achiral, by substituting one hydrogen by deuterium it becomes prochiral. Replacing another hydrogen by tritium, the molecule is now chiral A methyl group substituted with deuterium and tritium is often used in studying the mechanism of biosynthetic reactions...

The CPO can catalyze the bioepoxidation of terminal short-chain aliphatic alkenes as well. The stereoselectivity depends largely on the length of the carbon chain of the substrate, and the 1-methyl group is essential for stereoselectivity and activity. For 1,1-disubstituted terminal alkenes, with one substitute being the methyl group, the reactions yielded epoxides (R)-20 and (R)-22 with 94% and 95% ee, respectively (Scheme 13.4a). However, for similar substrates without methyl substituents, the... 

Unsymmetrically substituted dipyrromethanes are obtained from n-unsubstitued pyrroles and fl(-(bromomethyl)pyiToIes in hot acetic acid within a few minutes. These reaction conditions are relatively mild and the o-unsubstituted pyrrole may even bear an electron withdrawing carboxylic ester function. It is still sufficiently nucleophilic to substitute bromine or acetoxy groups on an a-pyrrolic methyl group. Hetero atoms in this position are extremely reactive leaving groups since the a-pyrrolylmethenium( = azafulvenium ) cation formed as an intermediate is highly resonance-stabilized. 

The allyl-substituted cyclopentadiene 122 was prepared by the reaction of cyclopentadiene anion with allylic acetates[83], Allyl chloride reacts with carbon nucleophiles without Pd catalyst, but sometimes Pd catalyst accelerates the reaction of allylic chlorides and gives higher selectivity. As an example, allylation of the anion of 6,6-dimethylfulvene 123 with allyl chloride proceeded regioselectively at the methyl group, yielding 124[84]. The uncatalyzed reaction was not selective. 

Reaction of various reagents (CH3I. CjHjI, PhCHO) on the organolithium products obtained by reaction of butyl-lithium with 2-methyl-4-phenylthiazole gives approximately 90% 5-substitution. The increased reactivity of the hydrogen in the 5-position can be explained by the fact that the -r J effect of a 4-methyl group would increase the electron... 

Methylthiazole-3-oxide in the same conditions gave both 4-ace-toxymethylthiazole and 2-acetoxy-4-methylthiazole but in low yields. The reaction of 2,4-dimethylthiazole-3-oxide with p-tolyl chloride has also been studied (268), substitution occurring on the 2- and 4-methyl groups. 

The least sterically hindered p hydrogen is removed by the base m Hofmann elim matron reactions Methyl groups are deprotonated m preference to methylene groups and methylene groups are deprotonated m preference to methmes The regioselectivity of Hofmann elimination is opposite to that predicted by the Zaitsev rule (Section 5 10) Elimination reactions of alkyltrimethylammonmm hydroxides are said to obey the Hofmann rule, they yield the less substituted alkene... 

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