Methylcyclohexanone, Reaction

TABLE 17.2 Formation of Enolates from 2-Methylcyclohexanone Reaction Conditions 17.35 17.36... 

Although the enamine (30) underwent addition reaction with ethyl azido-dicarboxylate, it failed to add another mole of jS-nitrostyrene. In a similar manner the morpholine enamine of 2-methylcyclohexanone also failed to react with this olefin, i.e., jS-nitrostyrene, which is undoubtedly due to the 1,3-diaxial interaction between the methyl group and the incoming electrophile in the transition state. 

The reactions of pyrrolidinocyelohexenes with acid have also been Considered from a stereochemical point of view. Deuteration of the 2-methylcyclohexanone enamine gave di-2-deuterio-6-methylcyclohexanone under conditions where ds-4-/-butyI-6-methyIpyrrolidinocycIohexene was not deuterated (2J4). This experiment supported the postulate of Williamson (2JS), which called for the axial attack of an electrophile and axial orientation of the 6 substituent on an aminocyclohexene in the transition state of such enamine reactions. These geometric requirements explain the more difficult alkylation of a cyclohexanone enamine on carbon 2, when it is substituted at the 6 position, as compared with the unsubstituted case. 

The illumination of enamines as general activa ting derivatives of ketones in alkylation reactions also threw light on their special usefulness for controlling alkylations (3), particularly in the formation of monosubstituted cyclohexanones. Thus 2-methylcyclohexanone could be obtained in 80% yield from the pyrrolidine enamine of cyclohexanone, and further alkylation, which required more drastic conditions, gave only 2,6-dimethylcyclo-hexanone (1,237). 

Since most often the selective formation of just one stereoisomer is desired, it is of great importance to develop highly selective methods. For example the second step, the aldol reaction, can be carried out in the presence of a chiral auxiliary—e.g. a chiral base—to yield a product with high enantiomeric excess. This has been demonstrated for example for the reaction of 2-methylcyclopenta-1,3-dione with methyl vinyl ketone in the presence of a chiral amine or a-amino acid. By using either enantiomer of the amino acid proline—i.e. (S)-(-)-proline or (/ )-(+)-proline—as chiral auxiliary, either enantiomer of the annulation product 7a-methyl-5,6,7,7a-tetrahydroindan-l,5-dione could be obtained with high enantiomeric excess. a-Substituted ketones, e.g. 2-methylcyclohexanone 9, usually add with the higher substituted a-carbon to the Michael acceptor ... 

Problem 19.4 How would you carry out the following reactions More than one step may be required, (a) 3-Hexvne 3-Hexanone, (b) Benzene —> m-Bromoacetophenone I (c) Bromobenzene —> Acetophenone (d) 1-Methylcyclohexene — 2-Methylcyclohexanone... 

The chemical yield of the classical Henry reaction is not always good and depends on steric factors thus, highest yields are obtained when nitromethane is used. Performing the reaction under high pressure (9 kbar, 30 °C) with tetrabutylammonium fluoride catalysis19 enlarges the scope of the reaction dramatically. Thus, addition of nitropropane to 2-methylcyclohexanone, which is not reactive under the classical conditions, was achieved in 40 % yield. Improved yields... 

High-boiling products found in this procedure and in similar experiments involving cyclohex-2-enone derivatives5 probably result from bimolecular reduction processes.15 3-Methylcyclohexanone, which arises by protonation rather than alkylation of the enolate (and which made up ca. 12% of the volatile products), is probably the result of reaction of allyl bromide with liquid ammonia to form the acidic species allyl ammonium bromide.5 10... 

CHMO is known to catalyze a number of enantioselective BV reactions, including the kinetic resolution of certain racemic ketones and desymmetrization of prochiral substrates [84—87]. An example is the desymmetrization of 4-methylcyclohexanone, which affords the (S)-configurated seven-membered lactone with 98% ee [84,87]. Of course, many ketones fail to react with acceptable levels of enantioselectivity, or are not even accepted by the enzyme. 

The low-temperature method is effective not only in the kinetic resolution of alcohols but also in the enantioface-selective asymmetric protonation of enol acetate of 2-methylcyclohexanone (15) giving (f )-2-methylcyclohexanone (16). The reaction in H2O at 30°C gave 28% ee (98% conv.), which was improved up to 77% ee (82% conv.) by the reaction using hpase PS-C 11 in /-Pt20 and ethanol at 0°C. Acceleration of the reaction with lipase PS-C 11 made this reaction possible because this reaction required a long reaction time. The temperature effect is shown in Fig. 14. The regular temperature effect was not observed. The protons may be supplied from H2O, methanol, or ethanol, whose bulkiness is important. 

Ecologically and economically valuable solvent-free Robinson annelation reactions, which proceed efficiently in a one-pot process at room temperature, have been reported [ 10]. For example, 2-methylcyclohexanone (59), methyl vinyl... 

Very significant acceleration in the rate of deprotonation of 2-methylcyclohexanone was observed when triethylamine was included in enolate-forming reactions in toluene. The rate enhancement is attributed to a TS containing LiHMDS dimer and triethylamine. Steric effects in the amine are crucial in selective stabilization of the TS and the extent of acceleration that is observed.18... 

The most common rearrangement reaction of alkyl carbenes is the shift of hydrogen, generating an alkene. This mode of stabilization predominates to the exclusion of most intermolecular reactions of aliphatic carbenes and often competes with intramolecular insertion reactions. For example, the carbene generated by decomposition of the tosylhydrazone of 2-methylcyclohexanone gives mainly 1- and 3-methylcyclohexene rather than the intramolecular insertion product. 

Oxidation of 4-methylcyclohexanone by addition of nitric acid at about 75°C caused a detonation to occur. These conditions had been used previously to oxidise the corresponding alcohol, but although the ketone is apparently an intermediate in oxidation of the alcohol, the former requires a much higher temperature to start and maintain the reaction. An OTS report, PB73591, mentions a similar violent reaction with cyclohexanone [1], Presence of nitrous acid is essential for the smooth oxidation of cycloalkanones with nitric acid to a, rw-hcxanedioic acids. Because high-purity nitric acid (free of nitrous acid) is now commonly available, addition of a little sodium or potassium nitrite to the acid is necessary before its use to oxidise cycloalkanones [2],... 

However, 3- or4-methylcyclohexanone is less reactive to nitromethane than cyclohexanone. Although 2-methylcyclohexanone does not react with nitromethane under the conventional conditions, under high pressure and a fluoride ion catalysis the reaction proceeds to give the P-nitro alcohol in moderate yields (Eq. 3.18).29... 

Butyl hypochlorite, reaction with cy-clohexylamine, 46, 17 2- -Butyl-2-methylcyclohexanone, 48,40... 

Silver fluoborate, reaction with ethyl bromide in ether, 46, 114 Silver nitrate, complexing with phenyl-acetylene, 46, 40 Silver oxide, 46, 83 Silver thiocyanate, 46, 71 Sodio-2-formyl-6-methylcyclohexanone, 48,41... 

Another example of the formation of a rearranged product is the palladium(0)-catalysed reaction of the enolate ion of 2-methylcyclohexanone with 3-methyl-3-nitro-l -butene... 

The present procedure is a general method for the preparation of monoalkylated ketones from enamines of aldehydes and ketones with electrophilic olefins. There are many advantages in this method of alkylation. Only monoalkylation occurs, even when such reactive species as acrylonitrile are used and, when a cyclic ketone like 2-methylcyclohexanone is used, reaction occurs only at the lesser substituted center. In a general base-catalyzed reaction, substitution occurs on the more substituted center. 

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