Alkyl methyl ketones

Oxidation. The use of l,4-ben2oquinone in combination with paHadium(Il) chloride converts terminal alkenes such as 1-hexene to alkyl methyl ketones in high yield (81%) (32). The quinone appears to reoxidi2e the palladium. 

Madsen and Lavvesson (6/), however, have reported recently that the treatment of /7-alkyl methyl ketones with morpholine in the presence of p-toluenesulfonic acid for a short period of time resulted in the formation of a mixture of condensation product of the ketone (122) and the corresponding dienamine (123). 

Similar results were encountered by Bianchetti et al. (i52), who found that e ketal derivatives of //-alkyl methyl ketones with morpholine led to the enamines of the condensation products of these ketones. The authors have Suggested the following probable mechanism for the dienamine formation. 

Buu-Hoi has shown that n-alkyl methyl ketones excluding ethyl methyl ketone, yield primarily 2-monosubstituted cinchoninic acids. It has been demonstrated that the products of the condensation of isatin with aryloxyketones are the corresponding 3-aryloxy-4-quinoline carboxylic acids rather than the isomeric 2-aryloxymethylcinchoninic acids.In the case of simple a-alkoxyketones such as 1-alkoxyethyl methylketones, the preferred products are the 2-alkoxyalkylcinchoninic... 

In 2000, Woodward et al. reported that LiGaH4, in combination with the S/ 0-chelate, 2-hydroxy-2 -mercapto-1,1 -binaphthyl (MTBH2), formed an active catalyst for the asymmetric reduction of prochiral ketones with catecholborane as the hydride source (Scheme 10.65). The enantioface differentiation was on the basis of the steric requirements of the ketone substituents. Aryl w-alkyl ketones were reduced in enantioselectivities of 90-93% ee, whereas alkyl methyl ketones e.g. i-Pr, Cy, t-Bu) gave lower enantioselectivities of 60-72% ee. 

Most aliphatic ketones can lose a proton from either of two carbon atoms adjacent to the carbonyl. The question of which of the possible carbanions or salts is the effective reagent in a given base-catalyzed reaction depends on the nature of the electrophilic reagent with which the ion subsequently reacts. Thus alkyl methyl ketones lose a primary proton in their reactions with alkali and iodine, alkali and an aldehyde, or alkali and carbon dioxide, but lose a secondary proton in certain other reactions. 

In the condensation of alkyl methyl ketones with esters, the primary hydrogen is the one lost as in the reactions previously discussed with carbon dioxide, aldehydes, etc. The reaction is with the more rapidly formed and less hindered ion rather than with the ion that would be present in higher concentration at equilibrium. 

The direct conversion of an a-amino acid into the corresponding a-acetylamino-alkyl methyl ketone, via oxazoline (azalactone) intermediates. The reaction proceeds in the presence of acetic anhydride and a base such as pyridine with the evolution of CO2. 

The acid-catalyzed condensation between alkyl methyl ketones and the diiminodinitrile 8 (Scheme 3), with removal of water, yields the dinitriles the reaction fails with other ketones. 2,2-Dimethoxyproprane in tetrahydrofuran (THF) gives a high yield of 9 (R = Me). ... 

Enantio-Differentiating Hydrogenation of Alkyl Methyl Ketones ... 

The usual selectivities are observed, with aryl alkyl ketones and alkyl methyl ketones being reduced with high enantioselectivity (1 -> 2 and 3 -> 4)). That 5 is reduced to 6 with high , with the reducing enzymes differentiating between an ethyl and an -pentyl group, is even more impressive. 

Oxidation of 1-alkenes to methyl ketones. This Pd catalyst allows air oxidation of 1-alkenes to alkyl methyl ketones in yields of about 350% (based on Pd). The oxidation is also possible under nitrogen (about 90% isolated yield), but then I is not functioning as a catalyst (equation 1). 2-Alkenes can be oxidized slowly in this way but a number of products are formed. 

Oxamborolidenes. There are noteworthy advances in the design, synthesis, and study of amino acid-derived oxazaborolidene complexes as catalysts for the Mukaiyama aldol addition. Corey has documented the use of complex 1 prepared from A-tosyl (S)-tryptophan in enantioselective Mukaiyama aldol addition reactions [5]. The addition of aryl or alkyl methyl ketones 2a-b proceeded with aromatic as well as aliphatic aldehydes, giving adducts in 56-100% yields and up to 93% ee (Scheme 8B2.1, Table 8B2.1). The use of 1-trimethylsilyloxycyclopentene 3 as well as dienolsilane 4 has been examined. Thus, for example, the cyclopentanone adduct with benzaldehyde 5 (R = Ph) was isolated as a 94 6 mixture of diastereomers favoring the syn diastereomer, which was formed with 92% ee, Dienolate adducts 6 were isolated with up to 82% ee it is important that these were shown to afford the corresponding dihydropyrones upon treatment with trifuoroacetic acid. Thus this process not only allows access to aldol addition adducts, but also the products of hetero Diels-Alder cycloaddition reactions. 

As Table 5 indicates, alkyl aryl ketones are the best substrates for this reaction. This has also been the case for the previously developed chiral ligand systems. Nevertheless, there have been substantial improvements in enantioselectivity for the reactions of alkenyl methyl ketones and alkyl methyl ketones, using Rh-catalysts with chiral ligands 195a191, 206b207, and 207209. 

Notes. (1) A temperature of 0 °C is used in the case of reactions involving methyllith-ium, i.e. for the preparation of alkyl methyl ketones. 

A general convenient alkyl methyl ketone synthesis, which utilises the /7-keto ester system as an intermediate, involves the acylation of a malonate ester by way of the ethoxymagnesium derivative. Hydrolysis and decarboxylation to the ketone is accomplished by heating in acid solution the synthesis of cyclohexyl methyl ketone is the illustrative example (Expt 5.96). 

A related synthesis of alkyl methyl ketones involves the preparation and alkaline cleavage of a 3-alkylpentane-2,4-dione which can be readily achieved in... 

With alkyl methyl ketones (R-CH2,CO,Me) the reaction is complicated by the presence of two alternative sites of oxidation in practice the methyl group appears to be oxidised in preference to the methylene group for reasons which have not been adequately clarified, but in any case the yields are usually poor. Unsubstituted, or symmetrically substituted cyclic ketones possessing of course an a-methylene group, are similarly converted into 1,2-diketones (e.g. the formation of cyclohexane-l,2-dione from cyclohexanone, Expt 5.99, cognate preparation) unsymmetrically substituted cyclic ketones would normally give rise to regioisomers. 

Alkyl methyl ketones undergo nitrosation at the reactive methylene group when treated with nitrous acid or an alkyl nitrite [Method (fi)]. The presence of hydrogen on the a-carbon permits tautomeric rearrangement to the oxime of a 1,2-dicarbonyl compound. Acidic hydrolysis of the oxime, which is best carried out in the presence of a hydroxylamine acceptor such as laevulinic acid,143 affords a further useful route to the 1,2-dicarbonyl system. 

Ab initio through-space/bond interaction analysis was applied to 3 + 2-anulation based on Brook rearrangement using /i-phcnylthioacryloylsilanes with alkyl methyl ketone enolates (Scheme 103).150 The major product has the large substituents on the same side of the five-membered ring. Orbital interactions related to the carbanion... 

Szollosi, G. and Bartok, M. Vapour-phase heterogeneous catalytic transfer hydrogenation of alkyl methyl ketones on MgO prevention of the deactivation of MgO in the presence of carbon tetrachloride, Appl.Catal., A, 1998, 169, 263-269. 

The butylated /3-ketoester C of Figure 10.23 is not the final synthetic target of the acetoacetic ester synthesis of methyl ketones. In that context the /3-ketoester C is converted into the corresponding /3-ketocarboxylic add via add-catalyzed hydrolysis (Figure 10.24 for the mechanism, see Figure 6.19). This /3-ketocarboxylic acid is then heated either in the same pot or after isolation to effect decarboxylation. The /3-ketocarboxylic add de-carboxylates via a cyclic six-membered transition state in which three valence electron pairs are shifted at the same time. The reaction product is an enol, which isomerizes immediately to a ketone in general and to phenyl methyl ketone in the specific example shown. In general, alkyl methyl ketones are obtained by such acetoacetic ester syntheses. 

The interactions of tellurium tetrachloride and aliphatic ketones in refluxing chloroform were investigated3. Reaction mixtures containing two mol of ketone per mol of tellurium tetrachloride yielded bis[2-oxo-l-alkyl] tellurium dichlorides (Vol. IX, p. 1060) from all alkyl methyl ketones investigated except ethyl methyl ketone. No tellurium dichlorides were isolated from analogous reactions with alkyl ethyl ketones or dipropyl ketones3. 

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