A-Diketones, synthesis

CgHeNj. Brown-yellow crystals m.p. 103-104 C, b.p. 256 258°C. Its solutions reduce Ag ions and it is used as a photographic developer. It is also used as a dye-precursor, for the synthesis of phenazine derivatives and for characterizing inter alia) a-diketones. 

The synthesis will therefore normally produce a 2,4-substituted pyrrole, with in addition an ester group or an acyl group at the 3-position, if a keto ster or a diketone respectively has been employed, and an ester group or an alkyl (aryl) group at the 5-position, according to the nature of the amino-ketone. 

Synthesis Only cyclohexanone can enolise, but the a-diketone is more electrophilic no control needed ... 

Synthesis and Properties. A number of monomers have been used to prepare PQs and PPQs, including aromatic bis((9-diamines) and tetramines, aromatic bis(a-dicarbonyl) monomers (bisglyoxals), bis(phenyl-a-diketones) and a-ketones, bis(phenyl-a-diketones) containing amide, imide, and ester groups between the a-diketones. Significant problems encountered are that the tetraamines are carcinogenic, difficult to purify, and have poor stabihty, and the bisglyoxals require an arduous synthesis. 

Monooximes of a-diketones have found applicability in the synthesis of 2-aminopyrazine 1-oxides by condensation with a-aminonitriles, and this reaction was used by White and coworkers in an approach to the synthesis of Cypridina etioluciferamine (Scheme 66 R = 3-indoloyl) (73T3761). In this instance, the use of TiCU as a catalyst was essential, since the carbonyl group in 3-acylindoles is normally deactivated and the required amine/carbonyl condensation is impractically slow. Under normal circumstances the carbonyl group in simple alkyl-substituted monoximes of a-diketones is the more reactive site and the reaction is rapid, requiring no catalysis (69LA(726)loo). 

In 1888 Claisen (1888CB1149) first recognized a general synthesis of isoxazoles (283) by the condensation-cyclization of 1,3-diketones (280) with hydroxylamine. It is now generally accepted that the monoxime (281) of the 1,3-diketone and the subsequent 5-hydroxy-isoxazoline (282) are the intermediate products of the reaction. The isolation of the monoxime (281) and 5-hydroxyisoxazoline (282), which were both readily converted into the isoxazole (283) by treatment with acid or base, has been reported (62HC(17)l). 

The reaction of appropriate 1,3-diketones (302) with hydroxylamine hydrochloride in pyridine (79MI41601) has been reported to result in a regiospecific synthesis of 3-alkyl-5-arylisoxazoles, as has the reaction of an a -bromoenone (307) with hydroxylamine hydrochloride in ethanol in the presence of potassium carbonate (81H(16)145). Regiospecific syntheses of 5-alkyl-3-phenylisoxazoles also result from the reaction of an a-bromoenone (307) with hydroxylamine in the presence of sodium ethoxide (81H(16)145). 3-Aryl-5-methylisoxazoles were prepared from phosphonium salts (304) and hydroxylamine (80CB2852). 

BREDERECK Imidazole synthesis Synthesis o( imidazoles Irom (ormamide (acetamide) and a-diketones, a-ketols, a-aminoketones, a-oziminoketones... 

Synthesis of ptendines from diaminopyrfmidines and a-diketones or a-ketoaldehydes. 

Though the dialdehyde-tropinone synthesis does not succeed when the dialdehyde is replaced by a diketone, Blount and Robinson have shown that 1-methyltropinone (XXXV) can be obtained by the interaction of the keto-aldehyde, laevulinaldehyde. Me. CO. CH. CH. CHO, with methylamine and calcium acetonedicarboxylate, and from this by reduction to 1-methyl- -tropine and benzoylation, 1-methyl tropacocaine (b.p. 210°/15 mm. picrate, m.p. 163-4°) has been prepared. 

The Hinsberg synthesis of thiophene derivatives describes the original condensation of diethyl thiodiglycolate and a-diketones under basic conditions which provides 3,4-disubstituted-thiophene-2,5-dicarboxylic acids upon hydrolysis of the crude ester product with aqueous acid. ... 

Separately, Paal and Knorr described the initial examples of condensation reactions between 1,4-diketones and primary amines, which became known as the Paal-Knorr pyrrole synthesis. Paal also developed a furan synthesis in related studies. The central theme of these reactions involves cyclizations of 1,4-diketones, either in the presence of a primary amine (Paal-Knorr pyrrole synthesis), in the presence of a sulfur(II) source (Paal thiophene synthesis), or by dehydration of the diketone itself (Paal furan synthesis). 

A solventless synthesis of pyrazoles, a green chemistry approach, has been described where an equimolar amount of the diketone and the hydrazine are mixed in a mortar with a drop of sulfuric acid and ground up. After an appropriate length of time ( 1 h) the product is purified to provide clean products. Even acyl pyrazoles 42 were obtained under the solvent-less reaction conditions in good yields. 

An illustrative example for the usefulness of the Weiss reaction for the construction of complex cyclopentanoid carbon skeletons is the synthesis of the all -cis [5.5.5.5]fenestrane 7 after Cook et al., starting from the a-diketone ... 

Cyclization—Continued a-diketone and ketone to a cyclo-pentadienone, 23, 92 indole synthesis, 23, 42 ketone phenylhydrazone to indole, 22, 98... 

A total synthesis of functionalized 8,14-seco steroids with five- and six-membered D rings has been developed (467). The synthesis is based on the transformation of (S)-carvone into a steroidal AB ring moiety with a side chain at C(9), which allows the creation of a nitrile oxide at this position. The nitrile oxides are coupled with cyclic enones or enol derivatives of 1,3-diketones, and reductive cleavage of the obtained cycloadducts give the desired products. The formation of a twelve-membered ring compound has been reported in the cycloaddition of one of the nitrile oxides with cyclopentenone and as the result of an intramolecular ene reaction, followed by retro-aldol reaction. 

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