Cyclohexanone tautomer

Most carbonyl compounds exist almost exclusively in the keto form at equilibrium, and it s usually difficult to isolate the pure enol. For example, cyclohexanone contains only about 0.0001% of its enol tautomer at room temperature, and acetone contains only about 0.000 000 1% enol. The percentage of enol tautomer is even less for carboxylic acids, esters, and amides. Even though enols are difficult to isolate and are present only to a small extent at equilibrium., they are nevertheless responsible for much of the chemistry of carbonyl compounds because they are so reactive. 

Cycloalkenone-2-carboxylates tautomerize to conjugated dienols in the presence of either acids or bases. Iron(III) catalysts have also been found to promote enone-dienol equilibration, and, at room temperature, dimerization64. Thus, treating 87 with 1 mol% iron(III) chloride hexahydrate in methylene chloride at room temperature affords 88 in 81% yield (equation 46). The cyclohexadiene-cyclohexanone is in a rapid equilibrium with its triendiol tautomer, 89 (equation 47). 

The enthalpy of reaction 38 is ca 13 kJ mol" for the case of cyclohexanone wherein R R = —(CH2)5—. This difference is compatible with intermolecular hydrogen bonding as would be found for the benzoquinone oxime tautomer. In order to understand the energetics of reaction 39, we derived the solid phase enthalpy of formation of nitrosobenzene... 

A way forward might be to form the imine 7.3 [and hence its enamine tautomer 7.4] by reacting the phenylamine 7.2 with cyclohexanone (Scheme 7.18). Then to generate the benzyne anion 7.5 by treating the tautomers with sodamide and sodium fcr/-buloxide in THF. Cydization to the required indole 7.1 occurs through nucleophilic addition to the benzyne, followed by protonation during work-up. 

A synthesis of 2-cyanocyclohexanone 4.45 from cyclohexanone is shown below. Formylation of cyclohexanone produces a mixture of keto/enol tautomers 4.42 and 4.43, the equilibrium lying to the side of the enol 4.42. Treatment with hydroxylamine affords isoxazole 4.44, and base-induced fragmentation of the isoxazole ring affords 4.45. Explain the regioselectivity of the isoxazole formation, and the mechanism of the fragmentation process. 

Selenium dioxide is able to a-oxygenate ketones via their enol tautomers. As is demonstrated in Figure 12.10 by the reaction of selenium dioxide with cyclohexanone, the actual electrophilic substitution product C is unstable. The latter contains selenium in the oxidation state +2 that takes the opportunity to transform into selenium in the oxidation state 0, i.e., elemental selenium, by way of the fragmentation reaction indicated. Thereby, the a-C O single bond of the primary product C is transformed into the a-C=0 double bond of the final product B (which, however, is largely present as the tautomeric enol A). 

Spectroscopic studies of imine-enamine tautomerism have shown that the equilibrium is almost completely in favour of the imine form for simple aldehydes and ketones372-374. Nevertheless, some secondary enamines are sufficiently stable to exist in detectable amounts in equilibrium with the corresponding imines for example, the f-butylamine imine of cyclohexanone shows signals due to the secondary enamine tautomer in the NMR spectrum (<5=CH 4.6)375. Studies of the imine-enamine equilibria have shown, as expected, that the enamine form is stabilized by methyl or aryl substituents at the -position (Scheme 189). 

The steric influence on the enamine-imine tautomerism has also been observed in the cyclic ketone derivatives. Cyclohexanone imines of w-propylamine, cyclohexylamine and 2-bornylamine show no signals ascribed to the enamine tautomer in their NMR spectra, but the /-butylamine38 does display signals of the enamine. In DMSO-d6 it comprises 38% of enamine 56 at equilibrium. The proportion of the 3,3,5,5-tetra-methylcyclohexanone and cyclopentanone enamines 57 and 58 is even higher, rising to 52% and 58%, respectively, in DMSO-d663. 

A second pathway which also contributes significantly to the adipic acid production, involves formation of 1,2-cyclohexanedione, perhaps by hydrolysis of the ketoxime tautomer of 2-nitrosocyclohexanone. Conversion of the ketoxime and of the diketone to adipic acid requires a vanadium(V) catalyst (Figure 10). The resulting vanadium(III) species, VO, is eventually reoxidized by nitric acid. The copper(II) apparently helps to reduce multiple nitrosation of cyclohexanone, as that eventually affords glutaric acid. 

Formyitttion of ketones. The condensation of cyclohexanone with ethyl formate in the presence of either sodium ethoxide or sodium hydride gives a product which can be described as 2-hydroxymethylenecyclohcxanone (I) or the tautomer 2-Tormylcyclohexanone (2) for simplicity Ihe pwcess is described us a formylation. In the procedure cited, formylulion was followed by reaction wllfr hydru/ine to... 

AA is probably generated via the intermediate formation of 2-hydroxycyclohexanone and 6-oxohexanoic acid. The mechanism may potentially include the formation of the enol tautomer of cyclohexanone, favored by the presence of an acid (Scheme 7.4 this may also be an alternative mechanism for cyclohexanone activation). The cyclohexen-l-ol formed is then oxidized to 2-hydroperoxycyclohexanone. The hydroperoxide generates 2-hydroxycyclohexanone, which is then cleaved to 6-oxohexanoic acid. The latter is then converted into AA via monoperoxyadipic acid this step is eventually catalyzed by cobalt. Scheme 7.5 shows the steps in the mechanism of reaction. 

Scheme 7.4 One possible mechanism of cyclohexanone activation via enol tautomer.

The tautomerism between cyclohexanone enamines 61 and the corresponding imines 62 has been investigated recently. Although NMR spectra in CDCI3 solution show only the presence of imines 62, the spectra recorded in DMSO-d solution indicate the existence of both tautomers. In agreement with the prediction by Ahlbrecht and coworkers " , the percent of the enamine tautomer 61 increases with the increase in the electron-withdrawing power of the substituent R, and the equilibria are completely on the imine side when R is p-methyl or /j-methoxy (equation 9). 

In the presence of a Lewis acid, alkyl 2-silyloxycyclopropanecarboxylates (14) react with a wide range of carbonyl compounds to give a diester (15), which has b n converted to a variety of furan derivatives (Scheme 18). An interesting use of the oxyanionic tautomer of a homoenolate involves the reaction of a magnesium cyclopropanolate (12) with the lithium enolate of cyclohexanone, from which a tricyclic ring containing a functionalized cycloheptanone (13) is formed in a single step (Scheme 18). ... 

The mechanism discussed above allows OYE to catalyze the dismutation of six-membered cyclic o ,/3-unsaturated ketones to the corresponding phenols and saturated ketones (Scheme 10). Oxidized OYE is reduced by cyciohexenone, producing reduced flavin and cyclohexadienone, the latter being the keto tautomer of the thermodynamically favored phenol. The reduced enzyme is then oxidized by cyciohexenone, producing cyclohexanone. 

Dehydrogenation of cyclohexanol to phenol can start with the formation of cyclohexanone intermediate (the stable tautomer of cyclohexenone ... 

Figure 8.1. An alcohol (cyclohexanol), enol (cyclohexenol), and phenol (phenol [hydroxybenzene]). Cyclohexenol is shown in equilibrinm with its tautomer cyclohexanone and, at room temperature, is present in low (ca. 10 %) concentrations relative to the ketone.

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