2- Methylcyclohexanone, hydrogenation

The presence of 1,3-diaxial interaction between the C-2 alkyl group and the C-4 axial hydrogen atom is reflected in the rate of enamine formation of 2-substituted cyclohexanone. It has been shown by Hunig and Salzwedel (20) that even under forcing conditions, the yield of pyrrolidine and morpholine enamines of 2-methylcyclohexanone does not exceed 58%, whereas the C-2 unsubstituted ketones underwent enamine formation under rather milder conditions in better than 80 % yield. 

Information regarding the position of the substituents can be obtained from the mass spectra of the enamines of cyclic ketones. For instance in the case of the morpholine enamine of 3-methylcyclohexanone, which is shown to be a 2 1 mixture of/ and isomers by NMR spectroscopy, the fragmentation of the radical ion from the /) isomer results in the loss of a methyl radical from the C-3 position. The d isomer gives a complicated spectrum due to the loss of the hydrogen radical. 

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. 

Further evidence for surface effects upon the stereochemistry of electrochemical reduction of ketones comes from the discovery that the nature of the cathode material may effect stereochemistry. Reduction of 2-methylcyclo-hexanone affords pure trans-2-methylcyclohexanone at mercury or lead cathodes, a mixture of cis and trans alcohols (mostly trans) at nickel, and pure cis alcohol at copper 81 >. Reduction could not be effected at platinum presumably hydrogen evolution takes place before the potential necessary for reduction of the ketone can be reached. 

Benzyl-6-methylcyclohexanone has been prepared by the hydrogenation of 2-benzylidene-6-methylcyclohexanone over a platinum or nickel catalyst, and by the alkylation of the sodium enolate of 2-formyl-6-methylcyclohexanone with benzyl iodide followed by cleavage of the formyl group with aqueous base. The 2,6-isomer was also obtained as a minor product (about 10% of the monoalkylated product) along with the major product, 2-benzyl-2-methylcyclohexanone by successive treatment of 2-methylcyclohexanone with sodium amide and then with benzyl chloride or benzyl bromide. Reaction of the sodium enolate of 2-formyl-6-methylcyclohexanone with potassium amide in liquid ammonia formed the corresponding dianion which was first treated with 1 equiv. of benzyl chloride and then deformylated with aqueous base to form 2-benzyl-2-methylcyclohexanone.i ... 

Biochemical reduction of a,/3-unsaturated ketones using microorganisms (best Beauveria sulfurescens) takes place only if there is at least one hydrogen in the /3-position and the substituents on a-carbons are not too bulky. The main product is the saturated ketone, while only a small amount of the saturated alcohol is formed, especially in slightly acidic medium (pH 5-5.5). The carbonyl is attacked from the equatorial side. Results of biochemical reduction of 5-methylcyclohex-2-en-l-one are illustrative of the biochemical reduction by incubation with Beauveria sulfurescens after 24 hours 74% of the enone was reduced to 3-methylcyclohexanone and 26% to 3-methylcy-clohexanol containing 55% of cis and 45% of trans isomer. After 48 hours the respective numbers were 70% and 30%, and 78% and 22%, respectively [878]. 

Figure 8 Guest-dependent polymorphism in CA inclusion crystals with (a) acetophenone, (b) y-valerolactone, (c) ethynylbenzene, (d) 2-fluoropropiophenone, (e) m-chloroaniline, (f) water (Form I), (g) water (Form II), (h) 3-methylcyclohexanone, (i) acetic acid, (j) m-fluoroaniline, (k) 1,2,3-trimethylbenzene, and (1) acrylonitrile. Hydrogen atoms are omitted for clarity. Carbon, nitrogen and oxygen atoms are represented by open, gray and tilled circles, respectively. 

TABLE 5.5. Hydrogenation of 4-Methylcyclohexanone over Platinum Metals in EthanoP ... 

Hydrogenation of 1,4- and 1,5-diketones over platinum metals may be accompanied by cyclization to give tetrahydrofurans and terahydropyrans, respectively.133,134 The hydrogenation of 2,6-heptanedione over Pt-C at 200°C in cyclohexane gave 40% of 2,6-dimethyltetrahydropyran, together with 43% of 3-methylcyclohexanone and 15% of 3-methylcyclohexanol, which resulted by an intramolecular aldol condensation and subsequent hydrogenation.134... 

TABLE 5.9 Cis / Trans Isomer Ratios of the Alcohols formed in Hydrogenation of Methoxy- and Methylcyclohexanones ... 

The preponderance of the A6 isomer in an equilibrium mixture of the pyrrolidine enamine of 3-methylcyclohexanone can be attributed to A(1,2) strain (2.5-3.3 kJ mol-1) between the quasiequatorial methyl group and the vinylic hydrogen atom in the A1 isomer75-77. Equilibrium between the A1 and A6 isomers of 3-substituted enamines takes place very readily at low temperatures78-80. When conjugation of the enamine with a 3-substituted aromatic ring is made possible, the A1 isomer is the predominant isomer81-89. 

Stereoselective selenenylation of ketones with chiral selenamines has been utilized as a facile entry to optically active 4-substituted 2-cyclohexenones 9, but with low optical purity6. Thus, the reaction of 4-te/T-butyl- or 4-methylcyclohexanone with chiral selenamines in benzene or tetrahy-drofuran at various temperatures and/or times affords diastereomeric 2-arylseleno-4-/< /7-butyl-and 2-arylseleno-4-methylcyclohexanone (8). Oxidation of these selenides with hydrogen peroxide produces (S)-4-/erf-butyl- or (.S )-4-methyl-2-cyclohexenone (9) in quantitative yield6. 

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