Subject 1,2-diketones

The bis(silyloxy)cyclobutenes are also subject to a variety of special reactions. Probably the most interesting is the observation that they readily undergo a ring-opening reaction leading to a butadiene derivative. This reaction has already been used to prepare large-ring diketones from cyclic 1,2-diesters. 

The initially formed ]5-dicarbonyl compounds are subject to further photo-transformations. One example is provided in the case of epoxy ketone (88), where the resulting /5-diketone (89) undergoes partly a-cleavage and acyl-alkyl... 

Selective fluonnation in polar solvents has proved commercially successful in the synthesis of 5 fluorouracil and its pyrimidine relatives, an extensive subject that will be discussed in another section Selective fluonnation of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of a/phn-fluoro ketones, fieto-diketones, heta-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluonde ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluonnation of pyridmes to give 2-fluoropyridines was shown to proceed through pyridine difluondes [50]... 

The photochemistry of transition metal 1,3-diketone chelate complexes has been known for some time [30,31], and their photophysical and photochemical properties and photocatalytic activity in different chemical reactions were reviewed in 1990 by Marciniak and Buono—Core [32]. Further discussion on the photochemistry of meta] chelate will not take place here since this subject is out of the scope of this chapter. 

Nalidixic acid is stable up to five years under reasonable conditions of temperature and humidity. Pawelczyk and Plotkowiakowa(17) subjected sodium nalidixate solutions to accelerated aging, but were unable to identify decomposition products. Detzer and Huber(lS) studied the photolysis and thermolysis of nalidixic acid in the presence of oxygen. Photolysis produced de-carboxylated nalidixic acid, structure A, and a diketone product, structure B, as well as carbon dioxide and ethylamine. 

Dioximes of a-diketones such as benzil on oxidation with IBTA are converted into 1,2,5-oxadiazole-A-oxides (furoxans) in high yields (75S445) (Eq. 35). Benzo- (Scheme 46) and pyrido-oxadiazoles (Eq. 36) are formed when o-nitroaniline and 3-amino-2-nitropyridine are subjected to similar oxidation. 

The preparation of 620, a tricyclic intermediate suited for elaboration into quadrone, has been reported by Monti and Dean Following introduction of the proper C5, stereochemistry by alkylation of 618 under kinetically controlled conditions, diketone 619 was subjected to acid-catalyzed rearrangement. After functional group manipulation, a tandem intramolecular aldol-pinacol rearrangement gave 620. 

Reactions of 4,7-phenanthroline-5,6-dione have been the subject of considerable study. It is reduced to 5,6-dihydroxy-4,7-phenanthroline by Raney nickel hydrogenation226,249 or by aromatic thiols in benzene,262 and oxidized by permanganate to 3,3 -bipyridyl-2,2 -dicarboxylic acid.263 It forms bishemiketals with alcohols226 and diepoxides with diazomethane.226 The diepoxides by reaction with hydrochloric acid form diols of type 57, R = Cl, which on oxidation with lead tetraacetate give 3,3 -bipyridyl diketones of type 58, R = Cl. Methyl ketones of type 58, R = H, are also obtained by lead(IV) acetate oxidation of the diol 57, R = H, obtained by lithium aluminum hydride reduction of 57, R = Cl. With phenyldiazomethane and diphenyldiazomethane the dione forms 1,3-dioxole derivatives,264,265 which readily hydrolyze back to the dione with concomitant formation of benzaldehyde and benzophenone, respectively. 

ACR139). The corresponding thieno[3,4-c]pyrroles (12) and (13) are also bleached by air and light, but the oxidation products have not been identified. However, the products from the reaction of thienopyrrole (13) and peracetic acid were identified as diketone (151) and its mono AT-phenylimine (154) showing that the pyrrole ring is subject to preferential oxidative attack (Scheme 45) (75ACR139). 

R = H) was observed with acetic acid. However, with propionic acid both isomers (414 and 415 R = Me) were formed in approximately equal amounts. It therefore appears that an initial acylation a to the carbonyl group, leading to the diketone, is followed by a second attack, the site of which is subject to subtle preferences (Scheme 137). 

Rearrangements of six-coordinate tris(diketonate) metal complexes have been the subject of numerous intense and careful investigations and the great body of literature has been incisively reviewed.77,283 A principal conclusion is that in no case has a unique rearrangement been unambiguously established and indeed, one may not exist. The difficulty arises from the consideration that the various five-coordinate transition states (or intermediates) which result from bond rupture processes can have quite similar energies. Thus, combinations of mechanisms can obtain which lead to extremely complicated DNMR spectra or isomerization kinetics. 

A somewhat arbitrary selection of areas is based on their perceived synthetic utility. P-Diketone and a-amino acid chelate reactions have received much attention over the years and the latter are still at the forefront of current activity. Finally, some reactions of simple ketones are affected by metal coordination and this subject will also be considered. 

The first ionic hexacoordinate complexes, silicon-tris-acetylacetonate cations (176), were reported as early as 1903 by Dilthey196a and Rosenheim and coworkers196b. Subsequently many other /i-diketonate complexes were studied197-199, and the subject was extensively reviewed7,200 and will not be discussed further here. 

When subjected to the action of propanethiol under basic conditions (pH 9.2), jatrophone (2) undergoes a Michael reaction across its C8-C9 double bond, followed by facile transannular cyclization to give the tetracyclic diketone 3.2,9 The susceptibility of this enone part structure to conjugate addition has been proposed to constitute the event responsible for the pronounced biological activity of 2.9... 

Intramolecular cyclisation of a 4-arylbutanoic acid system is also an important step in a convenient synthesis of the polycyclic system, chrysene, which is formulated and described in Expt 6.12. Here, methyl cinnamate is first subjected to reductive dimerisation to give methyl meso-ft,y-diphenyladipate, which is accompanied by some of the ( + )-form. The meso isomer (16) is the most easily isolable and cyclisation occurs smoothly in sulphuric acid to yield the diketone 2,1 l-dioxo-l,2,9,10,ll,18-hexahydrochrysene, which is obtained as the trans form (17) as shown in the following formulation. Clemmensen reduction of this ketone followed by dehydrogenation (in this case using selenium) completes the synthesis of chrysene. 

Diketones undergo a rearrangement in the presence of strong base to yield a-hydroxycarboxylic acids. The best yields are obtained when the subject diketones do not have enolizable protons. 

The keto-enol equilibrium of the 1,3-diketones has been the subject of intensive studies using various physical techniques and theoretical calculations [78-80], Recently, X-ray crystal analysis of acetylacetone (83) was carried out at 110 K, and it was found that it exists as an equilibrium mixture of the two enol forms 83b and 83c [81]. Room-temperature studies show an acetylacetone molecule with the enolic H-atom centrally positioned, which can be attributed to the dynamically averaged structure 83d. Application of a crystal engineering technique showed that a 1 1 inclusion complex of83 can be formed with l,l/-binaphthyl-2,2/-dicarboxylic acid in which the enol form is stabilized by a notably short intramolecular hydrogen bond [82],... 

Fig (14) Olefin (107) has been converted to cyclic ether (114) by standard reactions. Its transformation to enone (115) is accomplished by annelation with methyl vinyl ketone and heating the resulting diketone with sodium hydride in dimethoxyethane. The ketoester (116) is subjected to Grignard reaction with methyllithium, aromatization and methylation to obtain the cyclic ether (117). Its transformation to phenolic ester (119) has been achieved by reduction, oxidation and esterification and deoxygenation. 

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