Cyclohexanone, by oxidation

All that remains is to make cyclohexanone by oxidation of cyclohexanol. 

Nylon 6, commonly known as Perlon, in which the repeating units always contain six carbon atoms, is obtained by the polymerization of caprolactam. The first stage, as with the manufacture of nylon 66, is the reduction of phenol to cyclohexanol, which is converted into cyclohexanone by oxidation. The latter reacts with hydroxylamine to form an oxime. 

Using the above method, octan-2-ol gives corresponding ketone in 92.8% yield in 5 hr compared to 2% yield by mechanical stirring. Similarly, cyclohexanol gave 53% yield of cyclohexanone by oxidation under sonication (5 hr) compared to the 4% yield under usual conditions. 

Since adipic acid has been produced in commercial quantities for almost 50 years, it is not surprising that many variations and improvements have been made to the basic cyclohexane process. In general, however, the commercially important processes stiU employ two major reaction stages. The first reaction stage is the production of the intermediates cyclohexanone [108-94-1] and cyclohexanol [108-93-0], usuaHy abbreviated as KA, KA oil, ol-one, or anone-anol. The KA (ketone, alcohol), after separation from unreacted cyclohexane (which is recycled) and reaction by-products, is then converted to adipic acid by oxidation with nitric acid. An important alternative to this use of KA is its use as an intermediate in the manufacture of caprolactam, the monomer for production of nylon-6 [25038-54-4]. The latter use of KA predominates by a substantial margin on a worldwide basis, but not in the United States. 

The plant was a stage in the production of nylon. It manufactured a mixture of cyclohexanone and cyclohexanol (known as KA, for the ketone/alcohol naixture) by oxidizing... 

By oxidation with chromic acid, this is converted into cyclohexanone-3-carboxylic acid, in which the —CH. OH— group is converted into the —CO— group. This is converted into its ethyl ester and treated with magnesium methyl iodide, and the product, on hydrolysis, yields l-methyl-cyclohexane-l-ol-3-carboxylic acid, which is converted byhydro-bromic acid into 1-bromo-l - methyl - cyclohexane - 3 - carboxylic acid. When this is digested with pyridine, hydrobromic acid is eliminated and yields l-methyl-A -cyclohexane-3-carboxylic acid of the formula—... 

An alternative to cyclohexanones from phenols involves ring saturation to the alcohol, followed by oxidation 14). 

By oxidation in 100 cc of absolute toluol with 425 cc of cyclohexanone and 155 cc of a 20% aluminum isopropylate solution in absolute toluol and after repeated crystallizations from isopropyl ether or methanol, 24 grams of pure 17o-oxyprogesterone-17-caproate is obtained, MP 119° to 121°C (dense needles). 

The preparation of Pans-1,2-cyclohexanediol by oxidation of cyclohexene with peroxyformic acid and subsequent hydrolysis of the diol monoformate has been described, and other methods for the preparation of both cis- and trans-l,2-cyclohexanediols were cited. Subsequently the trans diol has been prepared by oxidation of cyclohexene with various peroxy acids, with hydrogen peroxide and selenium dioxide, and with iodine and silver acetate by the Prevost reaction. Alternative methods for preparing the trans isomer are hydroboration of various enol derivatives of cyclohexanone and reduction of Pans-2-cyclohexen-l-ol epoxide with lithium aluminum hydride. cis-1,2-Cyclohexanediol has been prepared by cis hydroxylation of cyclohexene with various reagents or catalysts derived from osmium tetroxide, by solvolysis of Pans-2-halocyclohexanol esters in a manner similar to the Woodward-Prevost reaction, by reduction of cis-2-cyclohexen-l-ol epoxide with lithium aluminum hydride, and by oxymercuration of 2-cyclohexen-l-ol with mercury(II) trifluoro-acetate in the presence of ehloral and subsequent reduction. ... 

FIGURE 1 Continuous process for the manufacture of e-caprolactone by oxidation of cyclohexanone with peracetic acid. 

Oxidation of cyclohexanone by thallic perchlorate has similar kinetics but includes an acidity dependence of the form (at 25°C, n = 1.3 M)... 

Kinetic data exist for all these oxidants and some are given in Table 12. The important features are (i) Ce(IV) perchlorate forms 1 1 complexes with ketones with spectroscopically determined formation constants in good agreement with kinetic values (ii) only Co(III) fails to give an appreciable primary kinetic isotope effect (Ir(IV) has yet to be examined in this respect) (/ ) the acidity dependence for Co(III) oxidation is characteristic of the oxidant and iv) in some cases [Co(III) Ce(IV) perchlorate , Mn(III) sulphate ] the rate of disappearance of ketone considerably exceeds the corresponding rate of enolisation however, with Mn(ril) pyrophosphate and Ir(IV) the rates of the two processes are identical and with Ce(IV) sulphate and V(V) the rate of enolisation of ketone exceeds its rate of oxidation. (The opposite has been stated for Ce(IV) sulphate , but this was based on an erroneous value for k(enolisation) for cyclohexanone The oxidation of acetophenone by Mn(III) acetate in acetic acid is a crucial step in the Mn(II)-catalysed autoxidation of this substrate. The rate of autoxidation equals that of enolisation, determined by isotopic exchange , under these conditions, and evidently Mn(III) attacks the enolic form. 

Preliminary results on the anaerobic oxidation of cyclohexanone by IrCle suggest that, although enolisation is rate-determining at pH 3 (when the oxidation rate is equivalent to the enolisation rate and the reaction is zero-order in oxidant but first order in acidity), the subsequent reaction of the radical is one of ligand-capture , viz. 

Fig. 12.15. Computational comparison of reactants (adducts) and transition structures for Baeyer-Villiger oxidation of 2-(trifluoromethyl)cyclohexanone by peroxytrifluo-roacetic acid. Reproduced from Org. Lett., 5, 4803 (2003), by permission of the American Chemical Society.

The mechanism of direct oxidation of cyclohexene to cyclohexanone by N20 mediated oxidation was analyzed by density functional theory (DFT) using B3LYP/6-31G approximation. A two-step reaction mechanism was predicted where the substituted 1,2,3-oxadiazoline ring system 5 forms as the first intermediate in the process before subsequent conversion to the cyclohexanone <1999JOC6710, 2003CC42, 2005MI177>. 

VA Itskovich. The Liquid-Phase Oxidation of Isomeric Cyclohexanones by Dioxygen. PhD Thesis Dissertation, Institute of Chemical Technology, Leningrad, 1970 [in Russian]. 

The oxidation of NH3 to NH2OH forms the basis of a process for the ammoximation of cyclohexanone to the oxime because the NH2OH formed in solution readily reacts with the ketone (non-catalytically) to give the oxime (231). Table XXX (165) illustrates the conversions and selectivites obtained for a few typical ketones and aldehydes. The ammoximation of aldehydes is faster than that of ketones. The oxime selectivity is also higher. The ammoximation of cyclohexanone by this method offers a more eco-friendly alternative route to the cyclohexanone oxime intermediate for the production of Nylon-6. The current route coproduces large quantities of ammonium sulfate and involves the use of hazardous chemicals such as oleum, halides, and oxides of nitrogen. 

Industry, in fact, has a major interest in these diesters as building blocks for nylon 6,6 and nylon 7,7 in the production of polyesters and polyamides. However, their present synthesis raises an environmental concern. For instance, the oxidation of cyclohexanone by nitric acid (for the preparation of adipic acid), accounts for more than 10% of the total yearly release of N2O, which is among the main gases responsible for the greenhouse effect. The reaction of Scheme 4.14 represents an eco-friendly alternative synthesis of a,(i)-diesters which uses green reagents and, relevantly, has a 100% atom economy. The overall process is mechanistically described as a retro-Claisen condensation. 

Nearly all the adipic acid manufactured, 98%, is made from cyclohexane by oxidation. Air oxidation of cyclohexane with a cobalt or manganese (II) naphthenate or acetate catalyst at 125-160°C and 50-250 psi pressures gives a mixture of cyclohexanone and cyclohexanol. Benzoyl peroxide is another... 

Caprolactam is discussed more completely in Chapter 11, Section 5. It is made from cyclohexane by oxidation to cyclohexanone-cyclohexanol mixture, formation of cyclohexanone oxime, and acid-catalyzed rearrangement. 

Adipic acid (1,4-butanedicarboxylic acid) is used for the production of nylon-6,6 and may be produced from the oxidation of cyclohexane as shown in structure 17.1. Cyclohexane is obtained by the Raney nickel catalytic hydrogenation of benzene. Both the cyclohexanol and cyclohexanone are oxidized to adipic acid by heating with nitric acid. 

K[Ru(0)(PDTA)].3Hj0 and Ru(0)(HEDTA) (PDTA=(propylenediaminetetra-acetate) -) are made by oxidation of K[Ru "Cl(PDTA.H)] or K[Ru" Cl(EDTA.H)] with PhIO electronic and ESR spectra were recorded. Rates and activation energies for epoxidation by stoich. Ru(0)(PDTA)] or Ru(0)(HEDTA)/water-dioxane of cyclo-alkanes were measured, as were those for oxidation of cyclohexane to cyclohexanol and cyclohexanone [632],... 

A. 1,2-Cyclohexanedione has been prepared by brominating cyclohexanone and treating the resulting 2,6-dibromocyclohexanone with aqueous potassium hydroxide to obtain the dihydroxy compound which loses water to yield the dione 3 by heating divinyl glycol with copper 4 and by oxidizing cyclohexanone with selenium dioxide in an ethanolic solution.5 6... 

The process starts from tricyclohexylidene triperoxide which is obtained by oxidation of cyclohexanone with hydrogen peroxide. Pyrolysis leads to a mixture of 1,16-hexadecanolide and cyclopentadecane. The latter is oxidized by oxygen under boric acid catalysis to cyclopentadecanol which is subsequently oxidized to cyclopentadecanone [124,124a]. 

In a side-reaction 10-15% carboxylic acids are produced by oxidative cleavage of the ketone enolates. The cleavage is favoured by higher temperatures e.g. cyclo-hexanol leads to 80% cyclohexanone and 16% adipic acid at 25 °C, whilst at 80 °C 5% ketone and 42% diacid are found. These acidic by-products are easily separated, since they remain in the alkaline solution during workup. The oxidation of 6 gave the acetal 7 as main product (28%) together with 4% of the ketone 8 and 56% of unchanged 6. The acetal 7 is probably formed by nucleophilic addition of the alcohol 6 at the activated triple bond of ketone 8. 

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