Y-diketone

Diketones. y-Diketones contain two carbonyl groups separated by two carbon atoms. With the exception of 2,5-hexanedione which is a high boiling Hquid, 1,4-diketones ate low melting white soHds with only faint odors. Lower members are soluble in organic solvents and water. Properties of representative 1,4-diketones are shown in Table 14. 

The reduction of ,/S-unsaturated y-diketones can conveniently be done with zinc in acetic acid. The following procedure is applicable to the reduction of the Diels-Alder adduct of quinone and butadiene (Chapter 8, Section II). 

Under different conditions (in aqueous electrolyte) the selectivity of the cleavage reaction may be perturbed by the occurrence51-53 of a dimerization process. Thus, while the major process remains the two-electron reductive pathway, 20% of a dimer (y diketone) may be isolated from the cathodic reduction of PhC0CH2S02CH3. The absence of crosscoupling products when pairs of / -ketosulphones with different reduction potentials are reduced in a mixture may indicate that the dimerization is mainly a simple radical-radical coupling53 and not a nucleophilic substitution. 

The y-keto nitriles shown in Table I were prepared by the cyanide-catalyzed procedure described here. This procedure is generally applicable to the synthesis of y-diketones, y-keto esters, and other y-keto nitriles. However, the addition of 2-furancarboxaldehyde is more difficult, and a somewhat modified procedure should be employed. Although the cyanide-catalyzed reaction is generally limited to aromatic and heterocyclic aldehydes, the addition of aliphatic aldehydes to various Michael acceptors may be accomplished in the presence of thioazolium ions, which are also effective catalysts for the additions. 

Figure 9.1 Chelating agents capable of forming cements, (a) 2-methoxyphenol type. Guaiacol Rj = = H. Eugenol Rj =-CH2-CH=CH2, Rj = H. (b) y -diketone type.

Alternatively, Ballini devised a new strategy to synthesize tri-alkylated pyrroles from 2,5-dialkylfurans and nitroalkanes <00SL391>. This method involves initial oxidation of 2,5-dimethylfuran with magnesium monoperoxyphthalate to cA-3-hexen-2,5-dione (6). Conjugate addition of the nitronate anion derived from the nitro compound 7 to 6 followed by chemoselective hydrogenation of the C-C double bond of the resulting enones 8 (obtained by elimination of nitrous acid from the Michael adduct) completes the conversion to the alkylated y-diketones 9. Final cyclization to pyrroles 10 featured improved Paal-Knorr reaction conditions involving reaction of the diketones with primary amines in a bed of basic alumina in the absence of solvent. 

Several chiral Ru complexes have been applied successfully for the asymmetric hydrogenation of a-, (3-, and y-diketones. Hydrogenation of an a-diketone, 2,3-butandione, catalyzed by an (i )-BINAP-Ru complex gives optically pure (R,R)-2,3-butanediol and the meso-diol in a ratio of 26 74 (Equation (73)).12a... 

A homoleptic bulky a,y-diketonate yttrium complex (fod = 1,1,1,2,2,3,3-heptafluoro-7,7-dimethyl-4,6-octanedionate) was immobihzed on MCM-41.280 ( s = 1140m g, Vp = 0.93 cm g, dp = 2.7 nm) and a monopodaUy anchored surface species 6 has been proposed (Scheme 12.5). As suggested by FTIR (strong band for the Si-OH stretch vibration) as well as metal and carbon analysis (circa 3.4 wt% Y, fod/Y circa 2) only around half of the silanol population has been consumed [110]. 

Conseqnently, the magnesinm chelate 71 can also react as a nucleophilic donor in aldol reactions. In the chemistry involving magnesium chelates, these two aspects model their mode of action as nucleophilic partners in aldol condensations. This is exemplified in aldol condensations of y-diketones . Thus, sodium hydroxyde catalyzed cyclization of diketone 73 to give a mixtnre of 3,5,5-trimethyl-cyclopent-2-enone 74 and 3,4,4-trimethyl-cyclopent-2-enone 75 in a 2.2/1 isomeric ratio (equation 100). When treated with magnesinm methanolate, the insertion of a a-methoxy carbonyl group as control element, as in 76, allows the formation of a chelated magnesium enolate 77, and the major prodnct is now mainly the aldol 78. This latter treated with aqueous NaOH provides the trimethylcyclopent-2-enones 74 and 75 in a 1/49 ratio. 

Problem 17.18 Prepare 2,5-hexanedione (a -y-diketone) from acetoacetic ester and any alkylating reagent. 

The base-catalyzed Michael addition of oxazolin-5-ones to alkynic ketones produces 4-(3-oxopropenyl) derivatives (405) (79CB3221). The latter compounds are cleaved on warming with oxalic acid dihydrate in acetic acid to y-diketones (406). The mechanism of this transformation corresponds to a vinylogous Dakin-West reaction (Scheme 90). 

Most 1-aminopyrroles have been synthesised from y-diketones and a substituted hydrazine. If the parent N- aminopyrrole is desired, a hydrolyzable hydrazine derivative is used, for example semicarbazide or an acyl- or sulfonyl-hydrazide (equation 182) (B-77MI30607). 

Thiophenecarbaldehydes add smoothly to a,f3-unsaturated ketones and nitriles under cyanide ion catalysis to form y-diketones (366) and y-ketonitriles (367) respectively (76CB534). The 2,5-dicarbaldehyde gives the bis-adduct (368). The aldehydes undergo normal reduction to the hydroxymethylthiophenes by sodium borohydride. However, electrochemical reduction of the 2,5-dialdehyde on a mercury electrode at pH 1-3 gives the bimolecular reduction product (369) as a mixture of meso- and ( )-forms in the ratio 7 3. Reduction with zinc and acetic acid gives only the meso -form of (369) (75CR(C)(280)165>. 

In contrast to titanium(IV) tetrachloride, which causes polymerization of a,3-unsaturated esters, aluminum triflate88 or aluminum-impregnated montmorillonite87b are excellent promoters of silyl ketene acetal additions to a,(3-unsaturated esters (Scheme 35). Similarly, the addition of silyl ketene acetals and enol silyl ethers to nitroalkenes, followed by Nef-type work-up, affords y-keto esters (216) and y-di-ketones (218), respectively (Scheme 35).89a>89b Mechanistically, the y-diketones (218) arise from Nef-type hydrolysis of an initial nitronate ester (217).89e 89d Mukaiyama reports that SbCls-Sn(OTf)2 catalyzes diastereoselective anti additions of silyl ketene acetals, silyl thioketene acetals and enol silyl ethers to a,(3-unsaturated thioesters (219).90... 

We now discuss y-diketones. Pilcher and coworkers131 show cyclohexane-1,4-dione (57) to have a gas-phase enthalpy of formation of —332.6 1.2 kJmol-1, i.e. 3.0 ... 

The addition of aldehydes to a,B-unsaturated sulfones yields y-diketones. ... 

These distonic superelectrophiles (145-147) have been characterized by low-temperature H NMR (and 13C NMR in the case of 147) from FSO3H-SbFs solution. Dication 146 was also studied by calorimetric studies to determine the heat of diprotonation of 2,5-hexanedione.48 It was found that the heat of diprotonation for the y-diketones (like 2,5-hexanedione) is about 5 kcal/mol less than expected, when compared to twice the heat of protonation of acetone or other monoketones. The destabilization of dication 146 by 5 kcal/mol can be the result of electrostatic effects, and it can be considered evidence for the superelectrophilic character of such dications. When 2,6-admantanedione is reacted in FSO3H—SbFj solution, the dication 148 is formed as a persistent species, observable by and 13C NMR.12 The carboxonium carbons of 148 are observed at Z I3C 247.7, while the mono-cationic species (149) has a carboxonium carbon at 513C 267.1. These 13C NMR data were interpreted as evidence for the increasing importance of the carboxonium-type resonance structure (148a) due to electrostatic repulsive effects. Some examples of aromatic diketones (i.e., diacetylbenzenes) have also been reported to produce bis-carboxonium dications in their protonation reactions in superacids.47... 

In a similar manner, by using a-nionochloracetone, tho y-diketone, acetonyl acetone, is obtained after hydrolysis16 ... 

The neuronopathic symptoms described above are caused by substances that attack and destroy the cell bodies of neurons. Another class of toxic effects occurs as the result of deterioration of nerve axons and its surrounding myelin. Symptoms resulting from this effect are called axonopa-thies. A classic toxicant cause of axonopathies is that of y-diketones, most commonly 2,5-hex-anedione ... 

Substances that can be metabolized to y-diketones, such as -hexane, which is metabolized to 2,5-hexanedione, cause the same disorders. Examples of the many other substances known to cause axonopathies are colchicine, disulhram, hydralazine, misonidazole, and insecticidal pyrethroids. Peripheral neuropathy is the most common kind of axonopathic disorder. However, other symptoms may be observed. Numerous cases of manic psychoses were produced in workers exposed to carbon disulfide, CS2, in the viscose rayon and vulcan rubber industries. 

Quinolyl)pyrazoIo[3,4-i7]pyridazincs were prepared by cyclocondensation reactions of an anilino-pyrazole acid with acetaldehyde <02JHC869>. Cyclopentadienyl-derived y-diketones and arylhydrazines condensed to 4-(l,4-diaryl-2//-cyclopent[d]pyridazin-2-yl)-benzenesulfonamides <02H(57)2383>. Sulfonated polyfphthalazinone ether sulfone)s 37 were prepared by polycondensation of 4-(4-hydroxyphenyl)phthalazinone 36 with various ratios of disodium 5,5 -sulfonylbis(2-fluorobenzenesulfonate) and bis(4-fluorophenyl)sulfone <02P5335>. 

Among the best studied of these morphologic abnormalities associated with toxic neuropathies are the large masses of neurolilaments that accumulate locally within axons during intoxication with 2,5-hexanedione (2,5-HD) and related y-diketones, as well as with acrylamide, p, 3-iminodipropionitrile (IDPN), and carbon disulfide. 

Significant data are available only on the a- and /S-diketones and structurally related ligands.283 A single tris-chelate cationic species of dimethylphthalate appears to be the sole representative of the y-diketone type. 

In general, 1,3-dicarbonyl compounds, which include y9-dialdehydes, y9-ketoaldehydes, y -diketones, and y -ketocarboxylic esters, can exist in solution or as the pure compound in three tautomeric forms the diketo form (4a), the cw-enoUc (4b), and the trans-enolic form (4c). 

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