Oxo-carboxylic acid

When side chains of two or more different kinds are attached to a cyclic component, only the senior side chain is named by the conjunctive method. The remaining side chains are named as prefixes. Likewise, when there is a choice of cyclic component, the senior is chosen. Benzene derivatives may be named by the conjunctive method only when two or more identical side chains are present. Trivial names for oxo carboxylic acids may be used for the acyclic component. If the cyclic and acyclic components are joined by a double bond, the locants of this bond are placed as superscripts to a Greek capital delta that is inserted between the two names. The locant for the cyclic component precedes that for the acyclic component, e.g., indene-A - -acetic acid. 

Oxo carboxylic acids formally derived from aldonic acids by replacement of a secondary CHOH group by a carbonyl group are called ketoaldonic acids (see 2-Carb-21). 

Hydrogenation of the carbonyl function is an important synthetic transformation and can be catalyzed by complexes of several transition metals including -among others- Co, Rh, Ru, Ir, and Os. In aqueous organometallic catalysis the first examples were given by the hydrogenation of water-soluble 2-oxo-carboxylic acids, 1,3-dihydroxyacetone and fmctose [47-54], later the same substrates were also used for testing new catalysts [29]. 

Acyl Meldrum s acids (83TH1 87TH1), easily accessible from carboxylic acid chlorides and Meldrum s acid, may be viewed as protected 3-oxo-carboxylic acid esters (78JOC2087). The latter offer the advantage... 

With diketene, intermediates of type (III) were isolated and subsequently cyclized under basic conditions following step (b). In the case of 3-oxo-carboxylic acid esters or 3-acyl Meldrum s acids, cyclization step (b) immediately follows reaction step (a), if a slight excess of amine is employed (85TH1 87TH1). Note that conversion of (III) to (V) involves the (IH)-enol (Table I cf. 75BSF2731). The relatively low yield in the case of malonic acid ester, as well as the failure of the reaction with the non-enolizable diphenyl phosphinylacetic ester and cyanoacetate, points to the participation of an enol structure of (III). 

Scheme 233 Formation of aliphatic flavour aldehydes and alcohols, a Biotechnological reaction sequence mimicking plant biosynthesis of C6 compounds (green notes ), b HomologoiK reaction sequence in fimgi leading to mushroom-like C8 compounds. The stoichiometric formation of w-oxo-carboxylic acids during hydroperoxide lyase cleavage is not depicted...

Esters of 4-oxo carboxylic acids, such as levulinic acid (Entry 5, Table 7.8) or 3-ben-zoylpropionic acid [103], can be cleaved under essentially neutral reaction conditions... 

Esterification of resin-bound alcohols with 3-oxo carboxylic acids (which readily undergo decarboxylation) or with malonic acid is best performed using the corresponding ketenes, which can be generated in situ by thermolysis of dioxinones or other precursors (Entries 6-9, Table 13.12). PEG can also be acetoacetylated with acetyl ketene generated by thermolysis [171]. 

One approach to tetrahydropyridinones is the Lewis acid mediated hetero-Diels-Alder reaction of electron-rich dienes with polystyrene-bound imines (Entries 3 and 4, Table 15.23). The Ugi reaction of 5-oxo carboxylic acids and primary amines with support-bound isonitriles has been used to prepare piperidinones on insoluble supports (Entry 5, Table 15.23). Entry 6 in Table 15.23 is an example of the preparation of a 4-piperidinone by amine-induced 3-elimination of a resin-bound sulfinate followed by Michael addition of the amine to the newly generated divinyl ketone. The intramolecular Pauson-Khand reaction of propargyl(3-butenyl)amines, which yields cyclopenta[c]pyridin-6-ones, is depicted in Table 12.4. 

Fig. 93 2-Hydroxy-4-oxo carboxylic acid derivatives by Co/NHPI-catalyzed radical additions...

Cyclic anhydrides react well with trimethyl(trifluoromethyl)silane however, a stoichiometric amount of tetrabutylammonium fluoride is required.23 For example, succinic anhydride undergoes efficient addition of trimethyl(trifluorometliyl)silane to initially form ail adduct, which upon hydrolysis affords the trifluoromethyl-substituted oxo carboxylic acid 27. Simple amides, such as benzamide and acetamide, do not react with trimethyl(trifluoromethyl)silane even when a molar quantity of tetrabutylammonium fluoride is used. Furthermore, lactams, such as caprolactam, do not react with trimethyl(trifluoromethyl)silane under similar conditions. An activated amide carbonyl, such as that in A -methylsuccinimide, however, reacts smoothly to afford an interesting adduct,71 which upon acid hydrolysis affords the hcmiaminal 28. 

Miscellaneous. Brucine greatly accelerates the decarboxylation of certain p-oxo carboxylic acids at rt (eq 15), as well as the decarbalkoxylation of p-oxo esters. In some cases the products of these reactions possess some (modest) enantiomeric excess. ... 

An electron transfer mechanism has been proposed to account for the formation of carbon dioxide on irradiation of alkyl pyruvates the yield of carbon dioxide is enhanced by the presence of electron acceptors such as methyl viologen. The dye-sensitized photo-oxidation of a-oxo-carboxylic acids and esters also leads to the production of carbon dioxide. An initial dye-substrate interaction rather than singlet oxygen appears to be responsible for this fragmentation. 

Aromatic aldehydes were carboxylated by treatment with carbon dioxide and potassium cyanide in the presence of DBU under pressure in dimethylfor-mamide at ambient temperature to give a-oxo carboxylic acids 259 or their cyanohydrin derivatives 260 (77JAP(K)27745). 

The photochemistry of ethyl esters of 2-oxo-carboxylic acids has the participation of both singlet and triplet excited states o. Triplet state lifetimes have been measured and the occurrence of Norrish type II splits in these molecules established. Other flash photolysis studies reported deal with the photoinduced tautomerism of 2-hydroxyphenazine °, 3-methylisoxazolo[5,4-b]pyridine °, and the photolysis of 4,4 -biphenylbiazide °. The tautomerism and phototautomerization of 4(3H)-pyridinethione has been examined theoretically by the infra red isolation technique . The effect of pressure on the photoinduced abstraction reaction of azanaphthalenes in mixed crystals of durene has also been studied. Photosolvolysis of arylmethanols also occurs in aqueous solutions of sulphuric acid . 

Reduction of unsaturated oximes without effect on the C=C double bond is best carried out by sodium amalgam at not too high a temperature. Quinone dioximes are best converted into the amines by use of sodium sulfide in boiling alcohol.115 Amino carboxylic acids are prepared from the corresponding oxo carboxylic acid oximes, catalytic reduction being in these cases the method of choice. 

Hydrogenolysis of the N-N bond may be coupled with hydrogenation of a C=C double bond.151 Sodium amalgam in an acid medium can also be used for this cleavage.152 Zinc in an acid solution converts arylhydrazones of oc-oxo carboxylic acids into <%-amino acids.19h Recently, N-N cleavage of 1,2-dialkylhydrazines has been observed when merely boiling them in N-hydro-chloric acid.153... 

Carboxylic anhydrides and alkylcadmiums give ketones in 50-70% yield 359 this reaction is also smooth with Grignard reagents, especially at low temperatures (—70°).365 Oxo carboxylic acids are obtained when alkylcadmiums or alkylzincs are treated with cyclic acid anhydrides359,366,367 or when a monoester monochloride of a dicarboxylic acid reacts with an isoalkyl-magnesium bromide.368 (The oxo group can be reduced by Clemmensen s... 

Cyclohexanedione is also readily alkylated at position 2, and the alkyl derivatives formed can be cleaved hydrolytically to <5-oxo carboxylic acids by alkali. Stetter has reviewed403 the syntheses carried out by himself and his colleagues by this method. 

A sulfonation flask (capacity 350 ml) is fitted with a stirrer, reflux condenser, dropping funnel, and thermometer. Sublimed aluminum chloride (0.24 mole) is placed in this flask with exclusion of moisture and dissolved or suspended in nitromethane or nitrobenzene, respectively (1 ml per g of the chloride). The temperature rises to 50-60°. When these components have cooled to 20° the oxo carboxylic acid (0.05 mole) is added this is followed by the acylating agent (0,1 mde) with cooling by running water. Rapid but brief evolution of gas sets in. The mixture is heated for 3 h at 80°, then cooled to about 10° and poured on ice (2 g per g of the chloride). Crude 2-aIkyI-l,3-cycIoaIkanedione separates it is collected, washed with cold water (10 ml), and recrystallized with charcoal from water. 

Aromatic 0-hydroxy carboxylic acids behave very similarly to fi-oxo carboxylic acids they sometimes lose carbon dioxide when merely boiled with water, but this is a general reaction when they are heated with pyridine, quinoline, aniline, or dimethylaniline. This behavior can certainly be ascribed to reaction of aromatic 0-hydroxy acids as the keto tautomer ... 

In the aliphatic series no other useful route has yet been found for the synthesis of aldehydes which is the outcome usually desired from this reaction. Results are, however, more favorable with aromatic oxo carboxylic acids their thermal decomposition results in elimination of both carbon monoxide and carbon dioxide, but it can be directed towards formation of the aldehyde by decarboxylating the anils of the oxo acid 39 these yield Schiff bases in the first place ... 

As mentioned above (page 1018), thermal decarbonylation of non-enolizable a>oxo carboxylic acids is preferably carried out with their anils, but it can also be effected by concentrated sulfuric acid. For example, phenylglyoxylic acid is cleaved to benzoic acid and carbon monoxide when gently warmed in concentrated sulfuric acid. Such decarbonylations catalysed by protonic acids are known also for normal carboxylic acids such as triphenylacetic59 and... 

Oxidative cleavage of cycloalkenes is an important reaction, usually affording co,a/-dicarboxylic acids e.g., adipic acid is formed on oxidation of cyclo-hexene by permanganate.114 If there is no hydrogen on one of the doubly bonded carbon atoms, the product is an oxo carboxylic acid, e.g., a>pinonic acid from a-pinene 115... 

A -Alkyl-A -nitroso a-amino-acids (163), on irradiation in solution or in the solid state, are converted into amidoximes (164) with eliminatipn of carbon dioxide. a-Oxo-carboxylic acids undergo oxidative photodecarboxylation via a pathway thought to involve electron transfer. Photoeiimination of carbon dioxide from esters has also been observed. Hindered biphenyls have been prepared in this way... 

A comprehensive review of asymmetric hydrogenation, mainly 2-oxo-carboxylic acids and their esters, over heterogeneous catalysts of Pt-alumina modified with alkaloids was presented in Chapter 5 of this book. Here some practical aspects of these catal5i ic systems will be considered. Thus, ethyl (i )-4-phenyl-2-hydroxybutyrate is an important intermediate for the synthesis of the angiotensin-converting enzyme inhibitor Benazepril (Scheme 7.20.) and other carboxyalkyl dipeptides like Enalapril (Scheme 7.21.)... 

Polyketides. Collective name for natural products produced biosynthetically by way of poly(/5-oxo-carboxylic acids). The name was derived in 1907 by Collie on the basis of the hypothesis that natural prt ucts may be formed by multiplication of ketene (HjCsC o) units. The P. chains are constructed on multienzyme complexes (polyketide synthases) from acetyl- and malonyl-CoA ( acetogenins) or also by use of propio-nyl- and/or butyryl-CoA. Depending on the number of building blocks the natural products ate classified as triketides (n=3), tetraketides (n=4), etc. 

Shilling WL (1966) Making lactams by the vapor phase reductive amination of oxo carboxylic acid compounds US 3235562 A... 

Li, Y.-C. Yu, J.Z. Simultaneous determination of mono-and dicarboxylic acids, omega-Oxo-carboxylic acids, midchain ketocarboxylic acids, and aldehydes in atmospheric aerosol samples. Environ. Sci. Technol. 2005, 39, 7616-7624. 

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