1,4-Cyclohexanedione hydrogenation

Conjugation is more important 1 3 Cyclohexanedione exists mainly in its enol form in spite of the fact that intramolecular hydrogen bonding is impossible due to the distance between the carbonyl group and the enohc —OH group... 

A solution of resorcinol (11 g) in sodium hydroxide solution (4.8 g of sodium hydroxide in 20 ml of water) is hydrogenated in the presence of 1.1 g of 5 % rhodium on alumina for 16-18 hours at 50 psi initial pressure in a Parr apparatus. The reduction stops after the absorption of 1 equivalent of hydrogen. The catalyst is removed by filtration through celite, and the aqueous solution is carefully acidified with concentrated hydrochloric acid at 0°. The crude product is collected by filtration, dried in air, and recrystallized from benzene to give 1,3-cyclohexanedione, mp 105-107. ... 

Diketones can be reduced usually in high selectivity to either an intermediate ketol or thediol (72). Selectivity to the ketol depends in large measure on both catalyst and solvent. In cyclohexane solvent, the maximal yield of ketol obtained on partial hydrogenation of biacetyl fell in the order 5% Pd-on-C (99%), 5% Rh-on-C (92%), 5% Pt-on-C (88%), 5% Ru-on-C (63%) from acetylacelone the descending order was 5% Pd-on-C (86%), 5% Rh-on-C (60%), 5% Ru-on-C(35%), 5% Pt-on-C (27%)(56) from 1,4-cyclohexanedione in isopropanol initial selectivity to the ketol fell in the sequence 5% Pd-on-SiO, (96%), 5% Ir-on-C (95%), 5% Ru-on-C (92%), 5% Pt-on-C (67%) (73). Generalizing from these data, it appears palladium is a good first choice to achieve maximal selectivity. 

Hydrolysis, of 2 benzyl 2 carbometh oxycyclopentanone with lithium iodide m 2,4 6-colhdme, 46, 7 of 7 butyrolactone to ethyl y-bromo-butyrate with hydrogen bromide and ethanol, 46, 42 of 2,5 dicarbethoxy 1 4-cyclohexane-dione to 1,4 cyclohexanedione, 46, 25... 

Lehn, which was obtained from a dynamic library of hydrogen-bonding building blocks [101]. This system involved the equilibration between different products resulting from the condensation of 5,5-dimethyl-1,3-cyclohexanedione (74) and 2-hydrazinopyridine (75) (see Scheme 38). 

Cyclic 1,3-diketones can also participate in this MCR. Thus, utilization of two equivalents of 1,3-cyclohexanedione or dimedone instead of (3-ketoesters led to hydrogenated acridine derivatives. However, when only one equivalent of cyclic 1,3-dicarbonyl is used in combination with one equivalent of (3-ketoester, unsym-metric 1,4-DHPs may be obtained (Scheme 3). For example, this reaction was applied to the synthesis of ZD0947, a potassium chaimel opener [20]. 

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). 

Selective hydrogenation of a diketone. 4-Hydroxycyclohexanone has not been obtained in satisfactory yield by selective hydrogenation of 1,4-cyclohexanedione under homogeneous conditions. However it can be obtained in 70% yield by hydrogenation of the dione in 2-propanol with 5% ruthenium on silica. Some other metals (platinum, iridium) are more reactive, but less selective. 

Discuss the relative importance of intramolecular hydrogen bonding versus conjugation in light of the fact that 1,3-cyclohexanedione exists mainly in its enol form. j... 

Cyclohexanediones Boron trifluoride etherate, 43 Cyclohexanes by hydrogenation of... 

A novel process for the construction of benzodihydrofurans via a procedure involving a heteroatom-directed photoarylation provided the basis for another total synthesis of ( )-lycoramine (299) (Scheme 32) (167). Thus, 339, which was obtained from 1,3-cyclohexanedione in two straightforward steps, was converted to 340 by sequential treatment with LiAlH4, methyl chloroformate, and aqueous acid. Epoxidation of 340 with alkaline hydrogen peroxide followed by... 

After Michael addition of 17 to 2-methyl-1,3-cyclohexanedione (19) and the first aldol condensation, the double bond in 20 is reduced to give 21. The acetoxy group in 21 is unmasked by hydrolysis and oxidation, and subsequent aldol condensation gives 22. Again, the terminal double bond in 22 is oxidized with PdCk to methyl ketone, and subsequent hydrogenation of the internal double bond affords the trione 23, from which the steroid A-ring 24 is formed by aldol condensation [34],... 

For example, according to Reichardt and references quoted by him (Reichardt 1988), the enol form of ethyl acetoacetate, CH3C(OH)=CHCOOC2H5, constitutes 65% of it in cyclohexane, 28% in toluene, 11.5% in acetone, and 5% in dimethylsulfoxide, due to competition between intra- and inter-molecular hydrogen bonding of the enol form. When such a competition is precluded, as in 5,5-dimethyl-l,3-cyclohexanedione, the opposite trend is observed there is 7% enol in toluene, 81% in acetone and 99% in dimethylsulfoxide (Reichardt 1988). In this case, the solvent with a higher electron pair donicity favours the hydrogenbonding enol form. 

Scheme 5.7 Hydrogenation pathway of 5,5-dimethyl-l,3-cyclohexanedione leading to 3,3-dimethylcyclohexanone.

Haloperoxidase activity is usually determined spectrophotometri-cally by the bromination or chlorination of 2-chloro-5,5-dimethyl-1,3-cyclohexanedione (monochlorodimedone MCD) using hydrogen peroxide as the oxidant of the halide (28) (Figure 2). This assay is convenient because of the large change in extinction coefficients between the enolate and the product. However, its use is constrained by the need for conditions that stabilize the enolate. In the early work on V-BrPO, the... 

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 selective partial hydrogenation of symmetric cyclic diketones was accomplished by interrupting the reaction after the consumption of one equivalent of hydrogen, which indicates a stronger mode of adsorption for the diketone than for the ketol product. 2 The hydrogenation of 1,4-cyclohexanedione (30) to the ketol (Eqn. 18.23) was catalyzed by nickel, copper, palladium, platinum, iridium, and ruthenium. Iridium was the most active and selective of these catalysts. Hydrogenations run over this catalyst in iso-propanol at 20°C and 6 atmospheres... 

Etter has described a crystalline hexamer composed of six molecules of cyclohexanedione. The molecules, each of which adopted a syn-anti configuration, self-assembled via six O-H -O hydrogen bonds (Fig. 26).47 Each ketone, similar to the hexamer of Hamilton, was located at the corner of a hexagon. In contrast to Hamilton, however, the cavity of the assembly accommodated a solvent molecule as... 

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