Of 1,4-cyclohexanedione

There are several laboratory methods useful for the preparation of suberic acid. One starting material is 1,6-hexanediol which can be converted to the dibromide with HBr. Reaction of the dibromide with NaCN gives the dinitrile which can be hydrolyzed to suberic acid. The overall yield is 76% (42). Another laboratory method is the condensation of 1,3-cyclohexanedione with ethyl bromoacetate foUowed by reductive cleavage to give suberic acid in 50% yield (43). 

The reaction of 20 g (0.177 mole) of 1,3-cyclohexanedione (Chapter 5, Section II) with 21.8 g (0.22 mole) of maleic anhydride and 0.1 g of/j-toluenesulfonic acid in 150 ml of isopropenyl acetate is conducted as described above to give about 70% of the recrystallized product, mp 156-159°. 

Scheme 45 Anodic addition of the anion of 1,3-cyclohexanedione to electron rich olefins.

To carry out MCRs of aminoazoles with aldehydes and cyclic CH-acids, the methods of green chemistry were also applied. For example, treatments of 3-methylisoxazol-5-amine and aromatic aldehydes with 1,3-cyclohexanedione, dimedone, 1,3-indanedione, or titronic acid were proceeded in water under micro-wave irradiation at 120°C [100] (Scheme 31). As a result, clean, efficient, and convenient procedures for the generation of polycyclic-fused isoxazolo[5,4-b] pyridines 71 were developed. An interesting fact is that, in the case of 1,3-cyclohexanedione, dihydropyridine s were obtained while in aU other cases only hetero-aromatized derivatives were isolated. No reason for this experimental fact was discussed in the article. 

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]. 

Application of 1,3-cyclohexanedione 103a (80CPB648) and dimedone 103b (89CB1323) gives the spiro derivatives of tatrahydrochromenes 217 (Scheme 81). 

On the basis of these findings, a pathway for this cydoaddition is proposed in Scheme 7.24. The first step is the nucleophilic attack of the carbon atom in the 2-position of 1,3-cyclohexanedione on the Cy atom of the allenylidene complex to give a vinylidene complex, which is transformed into an alkenyl complex by intramolecular nucleophilic attack of the oxygen atom of a hydroxy group of an enol on the C, atom of the vinylidene complex. By the use of Ic with its bulkier alkanethio moiety as a catalyst and at lower temperature, a subsequent intramolecular cyclization may be slow enough to make isolation of the alkylated product possible. 

Ketone (289, R1 = H) can be obtained (29% yield) by condensation of 1,3-cyclohexanedione with 1,2-dichloroethyl acetate (in the presence of ammonia),703 2-propargyl-1,3-cyclohexanedione (298, R = H) [obtained from 286 (R1 = H) and propargyl bromide], treated with ZnC03,... 

In an application of the Niki reaction,474 the alkylation of 1,3-cyclohexanedione with trans-1,4-dibromo-2-methyl-2-butene (a reaction previously mentioned in connection with compound 218 (Section IV,A,3,c,iv) leads to a similar product, without methyl groups in position 6.721... 

Oxazinanes 90 react with 1,3-cyclohexanediones, in acetic acid under reflux, to afford the alkylidene 1,3-diketone intermediate 91. Michael addition of a second equivalent of 1,3-cyclohexanedione then occurs to form the 1,5-dicarbonyl equivalent 92, which upon cyclodehydration furnishes tricyclic 4/7-pyrans (Scheme 30) <1996T14273>. 

The easy hydrogenolysis of 1,3-cyclohexanedione over palladium catalyst has been applied to the preparation of 3,3-dimethylcyclohexanone from 5,5-dimethyl-1,3-cyclohexanedione (eq. 5.40).129 The reaction pathway outlined in Scheme 5.7 has been suggested for this transformation. 1,3-Cyclohexanedione was also hydro-genolyzed to give cyclohexanol in a 95% yield over copper-chromium oxide at 200°C and 17.7 MPa H2.130... 

SCHEME 57. Various types of solid-state aggregation of /3-ketocarbonyl compounds (A) unsolvated dimer [(CH3C(OLi)CH-COOEt]2]222 (B) unsolvated hexameric [(CH3C(OLi)CHCOOBu-t]6223 (C) tetrasolvated dimer of 1,3-cyclohexanedione lithium enolate exhibiting both O—Li and O—H coordinations224... 

A short O- - -H distance (1.9 A) was found by Boche and coworkers for the weak ammonium enolate (p.Kbh = 24.3 in acetonitrile) derived from r-butyl a-acetoacetate237, and recently, clearly well-shaped crystals of 1,3-cyclohexanedione lithium enolate (LiCHD) solvated by two molecules of methanol or 2,2,2-trifluoroethanol have been isolated by slow evaporation of a methanol solution of LiCHD. In the aggregate pattern, both oxygens have intramolecular contacts at all available syn or anti lone-pair positions (Figure 2)224. 

FIGURE 2. Molecular arrangement of methanol solvated lithium enolate of 1,3-cyclohexanedione (LiCHD)224... 

Katrusiak, A. (1990). High pressure X-ray diffraction study on the structure and phase-transition of 1,3-cyclohexanedione crystals. Acta Crystallogr. B, 46,246-56. [239] Katrusiak, A. (1991). High pressure X-ray diffraction studies on organic crystals. Cryst. Res. Tech., 26, 523-31. [239]... 

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. ... 

In general, there is significant competition between C- and O-alkylation when the equilibrium concentration of the enol tautomer is relatively high, as in the case of 1,3-cyclohexanedione. ... 

Problem 22.3 Draw structures for the monoenol forms of 1,3-cyclohexanedione. How many enol forms are possible Which would you expect to be most stable Explain. 

Y,s-Diketo esters This reagent effects C-acylation of ketones. It is suitable for C-acylation of 1,3-cyclohexanedione. 

Reaction of diazocine 190 (see Section II,A,3) with phosgene afforded the oxadiazolone derivative 191 (79CPB2608). As mentioned earlier (see Section II,B,1), annelated diazocine 51 accompanied 50 (R = R1 = H) as a product of the Schmidt reaction of 1,3-cyclohexanedione. It was postulated, on the basis of ring-opened hydrolysis products (see Section IV,D), that 51 arose from annelation of 50 (R = R1 = H). [A 1,4-diazo-cinedione and its annelation product were also obtained (89AHC185), but it was determined that in this case annelation occurred at the intermediate seven-membered p-ketolactam stage, not on the diazocine that followed.]... 

M. C. Etter, Z. Urbanczyk-Lipkowska, D. A. Jahn, and J. Frye, Solid-state structural characterization of 1,3-cyclohexanedione and of a 6 1 cyclohexanedione-benzene cyclamer complex, a novel host-guest species, J. Am. Chem. Soc. 108, 5871-5876 (1986). 

Katrusiak, A. (1990). High-pressure X-ray diffraction study on the structure and phase transition of 1,3-cyclohexanedione crystals. Acta Cryst. B 46, 246-256. 

B.S. Hudson, D.A. Braden, D.G. Allis, T. Jenkins, S. Baronov, C. Middleton, R. Withnall C.M. Brown (2004). J. Phys. Chem. A, 108, 7356-7363. The crystalline enol of 1,3-cyclohexanedione and its complex with benzene vibrational spectra, simulation of structure and dynamics and evidence for cooperative hydrogen bonding. 

Thus, in the case of 1,3-cyclohexanediones, the 1 1 stoichiometric alkylidene 1,3-diketone intermediate 66 (R = CH2COCH2COMe/OEt) undergoes intramolecular cyclodehydration to 64 but in all other cases, it reacts with another molecule of the... 

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