Dicarbonyl compounds acidity

Alkyl methyl ketones undergo nitrosation at the reactive methylene group when treated with nitrous acid or an alkyl nitrite [Method (fi)]. The presence of hydrogen on the a-carbon permits tautomeric rearrangement to the oxime of a 1,2-dicarbonyl compound. Acidic hydrolysis of the oxime, which is best carried out in the presence of a hydroxylamine acceptor such as laevulinic acid,143 affords a further useful route to the 1,2-dicarbonyl system. 

Aldol, intramolecular Dicarbonyl compound. Acid or base p-Hydroxyaldehyde Only 5- or... 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

Cyclic diols give dicarbonyl compounds The reactions are faster when the hydroxyl groups are cis than when they are trans but both stereoisomers are oxidized by periodic acid... 

Most of the reactions of ester enolates described so far have centered on stabilized eno lates derived from 1 3 dicarbonyl compounds such as diethyl malonate and ethyl ace toacetate Although the synthetic value of these and related stabilized enolates is clear chemists have long been interested m extending the usefulness of nonstabilized enolates derived from simple esters Consider the deprotonation of an ester as represented by the acid—base reaction... 

Insertion Reactions. Isocyanates also may undergo iasertion reactions with C—H bonds. Acidic compounds, such as 1,3-dicarbonyl compounds (6), react readily at room temperature to form carboxyamides. At higher temperatures carboxyamides frequentiy undergo secondary reactions leading to cyclized products (33,34). 

Carbon—nitrogen double bonds in imines, hydrazones, oximes, nitrones, azines, and substituted diazomethanes can be cleaved, yielding mainly ketones, aldehydes and/or carboxyHc acids. Ozonation of acetylene gives primarily glyoxal. With substituted compounds, carboxyHc acids and dicarbonyl compounds are obtained for instance, stearoHc acid yields mainly azelaic acid, and a smaH amount of 9,10-diketostearic acid. 

It is customary to perform the condensation of 1,4-dicarbonyl compounds with hydrazines in the presence of mineral acid to avoid the formation of A-aminopyrroles. Contrary to early claims that 4,5-dihydropyridazines are formed <07CB4598), these compounds are now regarded as 1,4-dihydro derivatives 81CB564). 

C NMR, 6, 550 LCAO-MO calculations, 6, 557 melting point, 6, 555 methylation, 6, 565 reactions, 6, 558 with bromine, 6, 560 with 1,3-dicarbonyl compounds, 6, 565 with nitrous acid, 6, 565 ring opening, 6, 561 solubility, 6, 555 5-substituted... 

The chloride of triflic acid (trifluoromethanesulfonyl chloride) is an effective sulfonylating agent Like triflic anhydride, it usually reacts with alcohols and other nucleophiles with the formation of the corresponding derivatives of tnflic acid [69] However, in some reactions, it acts as a chlorinating reagent [98] The reactions of tnfluoromethanesulfonyl chloride with 1,3-dicarbonyl compounds or some carboxylic esters in the presence of a base result m the formation of chlonnated products in high yields (equation 49)... 

The major development in the Knorr pyrrole synthesis has been access to the amine component. For example, use of preformed diethyl aminomalonate with 1,3-diketones affords much higher yields of pyrroles 14. Reaction of 6-dicarbonyl compounds with hydroxylamine 0-sulfonic acid gives pyrroles 15 in one step. Weinreb a-aminoamides have found use in the Knorr pyrrole synthesis of a wide variety of pyrroles 16. °... 

The wide applicability of the PK reaction is apparent in the synthesis of pyrroles, for example, 45, en route to novel chiral guanidine bases, levuglandin-derived pyrrole 46, lipoxygenase inhibitor precursors such as 47, pyrrole-containing zirconium complexesand iV-aminopyrroles 48 from 1,4-dicarbonyl compounds and hydrazine derivatives. The latter study also utilized Yb(OTf)3 and acetic acid as pyrrole-forming catalysts, in addition to pyridinium p-toluenesulfonate (PPTS). 

The Pictet-Spengler reaction is one of the key methods for construction of the isoquinoline skeleton, an important heterocyclic motif found in numerous bioactive natural products. This reaction involves the condensation of a P-arylethyl amine 1 with an aldehyde, ketone, or 1,2-dicarbonyl compound 2 to give the corresponding tetrahydroisoquinoline 3. These reactions are generally catalyzed by protic or Lewis acids, although numerous thermally-mediated examples are found in the literature. Aromatic compounds containing electron-donating substituents are the most reactive substrates for this reaction. 

The condensation of 1,3-dicarbonyl compounds 1 with amidines 2 catalyzed by acids or bases to give pyrimidine derivatives 3 is regarded as the Pinner pyrimidine synthesis. ... 

This type of synthesis has been used extensively in the preparation of hydroxamic acids resembling aspergillic acid. a-Aminohj droxamic acids react with a-dicarbonyl compounds to yield pyrazine hydroxamic acids (18). Glyoxal and diacetyl react readily, but poor... 

The reaction of 3-amino-4-cyanofurazan with (3-dicarbonyl compounds in the presence of catalytic amounts of nickel acetylacetonate (Ni(acac)2) gave labile enamines that on treatment with acetic acid afforded fused pyridines of type 100 in 80-95% total yields (Scheme 51) (94MC57). Eurther syntheses of furazano-pyridines can be found in the review by Sheremetev (99RCR137, 99UK154). 

Reactions of telluradiazoles 69 and their analogues 73 and 75 were not studied in detail. Compounds 69 are stable with respect to air and moisture, but decompose when exposed to sunlight. Acidic hydrolysis of telluradiazoles gives dicarbonyl compounds, ammonium salts, Te, and H2Te03. 

The high acidity of ct-nitroketones makes it possible to perform the Henry reacdons or Michael addidons under extremely rruld condidons The reacdon proceeds in the presence of catalydc amounts of Ph-vP to give the C-C bond formadon products under nearly neutral condidons Thus, 1,5-dicarbonyl compounds and ct-methylenecarbonyl compounds are prepared by the denitradon of ct-nitroketones, as shown in Eqs 7 67 and 7 68, respecdvely... 

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