Methyl group, reactivity with carbonyl compounds

This sequence serves to exemplify the formation and aspects of reactivity of toluene-p-sulphonate esters in monosaccharide systems, and further to illustrate the selective protection afforded to hydroxyl groups by the formation of cyclic acetals by reaction with carbonyl compounds. Thus reaction of methyl a-D-glucopyranoside (26) with benzaldehyde in the presence of zinc chloride gives the 4,6-acetal (27) (Expt 5.118), wherein two fused six-membered rings of the frans-decalin type are present. As a cognate preparation the reaction of benzaldehyde with methyl a-D-galactopyranoside results in a similar conversion to a 4,6-acetal, but in this case the product is the conformationally flexible system of the cis-decalin type, the most likely conformation being that shown below. 

Analogs. The ester enolates derived from methyl or t-butyl trimethylsilylacetate react in an analogous manner to ethyl ester (1) with carbonyl compounds. However, with the t-butyl ester the carbonyl reactant has to be an aldehyde as steric problems result in enolization of ketonic substrates. As with the ethyl ester, addition of the enolate to the carbonyl substrate may allow for stereochemical control of the resultant a , -unsaturated ester geometry. In addition, the groups attached to silicon can be modified without substantial changes to the reactivity with carbonyl confounds. ... 

Isatin (190) is a compound with interesting chemistry. It can be iV-acetylated with acetic anhydride, iV-methylated via its sodium or potassium salt and O-methylated via its silver salt. Oxidation of isatins with hydrogen peroxide in methanolic sodium methoxide yields methyl anthranilates (81AG(E)882>. In moist air, O-methylisatin (191) forms methylisatoid (192). Isatin forms normal carbonyl derivatives (193) with ketonic reagents such as hydroxylamine and phenylhydrazine and the reactive 3-carbonyl group also undergoes aldol condensation with active methylene compounds. Isatin forms a complex derivative, isamic acid (194), with ammonia (76JCS(P1)2004). 

A methyl group in the 2-position of the selenazole ring shows the same reactivity as the analogous thiazoles toward carbonyl compounds. By reaction of 2,4-dimethylselenazole with benzaldehyde in the presence of anhydrous zinc chloride catalyst, 4-methyl-2-styryl-selcnazole (9), mp 74-75°C, could be prepared. ... 

Other compounds with reactive methylene and methyl groups are completely analogous to the nitroalkanes. Compounds with ketonic carbonyl groups are the most important. Their simplest representatives, formaldehyde and acetone, were considered for many decades to be unreactive with diazonium ions until Allan and Podstata (1960) demonstrated that acetone does react. Its reactivity is much lower, however, than that of 2-nitropropane, as seen from the extremely low enolization equilibrium constant of acetone ( E = 0.9 x 10-7, Guthrie and Cullimore, 1979 Guthrie, 1979) and its low CH acidity (pK = 19.1 0.5, Guthrie et al., 1982). ... 

The intermediate cyclooctene complex appears to be more reactive with respect to CS coordination and more sensitive to oxidation when the arene ring bears electron-withdrawing groups (e.g., C02CH3). Dicarbonyl(methyl rj6-benzoate)-thiocarbonyl)chromium is air stable in the solid state and reasonably stable in solution.9 The infrared spectrum exhibits metal carbonyl absorptions at 1980 and 1935 cm"1 and a metal thiocarbonyl stretch at 1215 cm"1 (Nujol) (these occur at 1978, 1932, and 1912 cm"1 in CH2C12 solution).10 Irradiation of the compound in the presence of phosphite or phosphine leads to slow substitution of CO by these ligands, whereas the CS ligand remains inert to substitution. The crystal structure has been published."... 

Data for aliphatic aldehyde enolisation are very scarce, probably because the enolisation process is often complicated by oxidation and hydration. Nevertheless, the rate constants for base- and acid-catalysed iodination of R R2CHCHO were determined in aqueous chloroacetic acid-chloroacetate ion buffers (Talvik and Hiidmaa, 1968). The results in Table 4 show that alkyl groups R1 and R2 increase the acid-catalysed reactivity in agreement with hyperconjugative and/or inductive effects. This contrasts with aliphatic ketones for which steric interactions are important and even sometimes dominant. Data for base-catalysis are more difficult to interpret since a second a methyl group, from propionaldehyde to isobutyraldehyde, increases the chloroacetate-catalysed rate constant. This might result from a decrease of the a(C—H) bond-promoted hyperconjugative stabilisation of the carbonyl compound... 

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