1,2-Cyclohexanedione Cyclohexanone

Polychlorinated cyclohexanediones. Cyclohexanone and its methyl derivatives react with a large excess of CuClj 2H2O in refluxing 50% acetic acid or 50% dioxane (2 hr.) to give dichloro or trichloro derivatives of cyclohexane-1,2-dione in 60-70% yield. 

The coupling product is considered to involve a radical intermediate formed by one-electron oxidation, probably effected by Cr(IV). Similarly, the oxidation of cyclohexanone involves 2-hydroxycylohexanone and 1,2-cyclohexanedione as intermediates.208... 

Cyclohexanedione has been prepared by hydrolysis and decarboxylation of 2,5-dicarbethoxy-l,4-cyclohexanedione by using concentrated sulfuric acid, aqueous alcoholic phosphoric acid, or water at 195-200°, and by peroxyvanadic acid oxidation of cyclohexanone. 

Removal of the bulky, amorphous selenium is accomplished with the aid of a 6-in. Buchner funnel. The selenium is returned to the reaction flask and extracted with 300 ml. of boiling 95% ethanol for 1 hour (Note 4). The solution, obtained by decantation from the compact gray selenium, is combined with the above filtrate in a 4-1. distilling flask. Distillation under reduced pressure gives two fractions. The lower-boiling fraction (25-60°/16 mm.) consists mainly of ethanol, water, dioxane, and cyclohexanone the higher-boiling one (60-90°/16 mm.) contains cyclohexanone and 1,2-cyclohexanedione with traces of water and dioxane. The yield of crude product is approximately 322 g. 

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... 

A more convergent synthesis of frovatriptan using the methylamino-substituted cyclohexanone equivalent 75 is shown in Scheme 25.° The mono-ketal of 1,4-cyclohexanedione (74) was treated with methylamine in ethanol and then hydrogenated to give 75 as an oil, which was converted to the hydrochlonde salt. The hydrazine of 76, formed in situ by treatment with sodium nitrite followed by reduction of the diazonium salt with sodium dithionite, was reacted with 75 and additional concentrated HCl at 70 °C to deliver racemic frovatriptan (rac-6). 

Iodosobenzene diacetate in the presence of base converts cyclohexanone into a-hydroxycyclohcxanonc in 80% yield. A related reaction is the conversion of iso-phorone into the enol of 3,5,5-trimethyl-l,2-cyclohexanedione (equation IH). This... 

The double bond of the enol form of 1,4-cyclohexanedione is not conjugated with the carbonyl group. Its enol content is expected to be similar to that of cyclohexanone. 

Ozonolysis. Ozonolysis of cyclohexanone O-methyl oxime 163 in the presence of 1,4-cyclohexanedione 164 gave a complex reaction mixture containing hydroxylamines 164, as a main product (Scheme 71 <1997T5463>). 

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. 

When cyclohexanone forms via a cyclohexyl radical, a similar sequence of reactions occurs at the carbon a to the carbonyl group affording 1,2-cyclohexanedione which is eventually cleaved to adipic acid. 

Hence, the first clearcut evidence for the involvement of enol radical cations in ketone oxidation reactions was provided by Henry [109] and Littler [110,112]. From kinetic results and product studies it was concluded that in the oxidation of cyclohexanone using the outer-sphere one-electron oxidants, tris-substituted 2,2 -bipyridyl or 1,10-phenanthroline complexes of iron(III) and ruthenium(III) or sodium hexachloroiridate(IV) (IrCI), the cyclohexenol radical cation (65" ) is formed, which rapidly deprotonates to the a-carbonyl radical 66. An upper limit for the deuterium isotope effect in the oxidation step (k /kjy < 2) suggests that electron transfer from the enol to the metal complex occurs prior to the loss of the proton [109]. In the reaction with the ruthenium(III) salt, four main products were formed 2-hydroxycyclohexanone (67), cyclohexenone, cyclopen tanecarboxylic acid and 1,2-cyclohexanedione, whereas oxidation with IrCl afforded 2-chlorocyclohexanone in almost quantitative yield. Similarly, enol radical cations can be invoked in the oxidation reactions of aliphatic ketones with the substitution inert dodecatungstocobaltate(III), CoW,20 o complex [169]. Unfortunately, these results have never been linked to the general concept of inversion of stability order of enol/ketone systems (Sect. 2) and thus have never received wide attention. 

Phenols can be partially hydrogenated in the presence of alkali to cyclohexanones. An example is the synthesis of dihydroresorcinol, or l,>cyclohexanedione, by hydrogenation of resorcinol in the presence of Raney nickel and an equimolar quantity of sodium hydroxide (95%). Under these same conditions, pyrogallol furnishes a stable enediolone. ... 

The palladium catalyzed hydrogenolysis of 5,5-dimethyl 1,3-cyclohexane-dione (59) in acidic medium gave good yields of the cyclohexanone, 60 (Eqn. 20.41). 5 In iiie absence of acid, a platinum catalyst gave a higher selectivity for the hydrogenolysis of one of the carbonyl groups of 1,3-cyclohexanedione than did palladium. ... 

A review by Schuchardt et al. thoroughly analyses the various catalytic systems reported in the literature up to 2000, both homogeneous and heterogeneous ones, and those that use oxidants other than oxygen [e.g., HP or t-butyl hydroperoxide (f-BuOOH)[ [2c[. The mechanism involves the formation of cyclohexanol via the cyclohexyl radical and cyclohexyl hydroperoxide. According to the Haber-Weiss mechanism, cyclohexyl hydroperoxide decomposes into alkoxy and alkyloxy radicals (Section 7.2.1). Cyclohexanol is finally oxidized to cyclohexanone. A similar mechanism may occur at the a-C, affording 1,2-cyclohexanedione, which is finally cleaved to AA. Oxidation of the intermediately formed cyclohexanone to AA then occurs through a mechanism similar to that illustrated in Scheme 7.5. 

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