HYDROXY MALONIC ACIDS

Methyl- and 3-phenyl-4-hydroxy-2-oxo-2//-pyrido[2,1 -Z)]oxazinium inner salts were prepared in the reaction of 2-pyridone and 2-substituted malonyl chloride, prepared in situ from 2-substituted malonic acid with PCI5 in CH2CI2 (00JCS(P2)2096). 

When the three ligands are the same, procedures similar to the ones developed by Hellwinkel [16,17], Koenig [25-28] and coworkers can be utilized -that is the one-time addition of three equivalents of bidentate ligands to PCI5 to afford the hexacoordinated phosphate anions. Ligands as varied as malonic acid,3,3,3-trifluoro-2-hydroxy-2-trifluoromethyl-propionic acid or oxalic acid have been used to form 5,6, and 7,respectively [29]. Aromatic 1,2-diols are also particularly good ligands as tetrachloropyrocatechol [30, 31], 4-methylpyro-... 

Bohman and Allenmark resolved a series of sulphoxide derivatives of unsaturated malonic acids of the general structure 228. The classical method of resolution via formation of diastereoisomeric salts with cinchonine and quinine has also been used by Kapovits and coworkers " to resolve sulphoxides 229, 230, 231 and 232 which are precursors of chiral sulphuranes. Miko/ajczyk and his coworkers achieved optical resolution of sulphoxide 233 by utilizing the phosphonic acid moiety for salt formation with quinine. The racemic sulphinylacetic acid 234, which has a second centre of chirality on the a-carbon atom, was resolved into pure diastereoisomers by Holmberg. Racemic 2-hydroxy- and 4-hydroxyphenyl alkyl sulphoxides were separated via the diastereoisomeric 2- or 4-(tetra-0-acetyl-D-glucopyranosyloxy)phenyl alkyl sulphoxides 235. The optically active sulphoxides were recovered from the isolated diastereoisomers 235 by deacetylation with base and cleavage of the acetal. Racemic 1,3-dithian-l-oxide 236... 

Sorbic acid has been prepared from crotonaldehyde 1 5 or aldol6 and malonic acid in pyridine solution by hydrogen peroxide oxidation of the condensation product of crotonaldehyde and pyruvic acid 7 and by the action of alkali on 3-hydroxy-4-hexenoic acid,8 9 /3,5-disulfo-w-caproic acid,10 and parasorbic acid.1112... 

Higher-molecular-weight normal 2-alkenoic acids have been prepared in poor yields by the Doebner condensation of aldehydes with malonic acid,5-7 and by the Reformatsky reaction of aldehydes with ethyl bromoacetate followed by dehydration.8 The a-iodo acid, prepared from the bromo acid, has been dehydrohalogenated with potassium hydroxide in ethanol,9 but large quantities of the a-hydroxy acid are formed as a by-product which is difficult to separate in some instances. The present procedure is an adaptation of a published method.6... 

Hydroxy-4-methylthiazole-2(3//)thione carbamates, e.g. the cyclohexyl derivative 336, are precursors for monoalkylaminium cation radicals, which cannot be prepared from 2-thioxopyridinyloxycarbamates. The carbamate is obtained from 3-hydroxy-4-methylthiazole-2(3//)-thione and cyclohexyl isocyanate. When irradiated in the presence of malonic acid and /-butyl hydrogen sulphide it yields the cyclohexylaminium cation... 

Bis-p-nitrophenyl malonate (55M29) reacts with a-alkylamino-isobutyr-onitriles in xylene to give derivatives (16b) of tetramic acids with yields of 30-50% (86UP1 88UP1). The reaction of derivatized malonic acids with a-amino acid esters to 3-alkoxycarbonyl-l,5-dihydro-4-hydroxy-2-pyrrolones presents the same problems (see Section III). (See Fig. 8.)... 

The reaction of 2,2-dimethyl-4,6-dioxo-l,3-dioxane (Meldrum s acid 394) and its analogues with 3-dialkylaminophenols has been used to prepare some fluorescent 7-dialkylamino-4-hydroxycoumarins (Scheme 127) (77M499). The substituted malonic acid (395) or its dehydration product is a possible intermediate, since it is known that diaryl-malonic esters are accessible from phenols and the 1,3-dioxane. 3-Methoxyphenol yields the pyrano[3,2-c]benzopyran-2,5-dione (396) in this reaction, presumably by annelation of another ring on to initially formed 4-hydroxy-7-methoxycoumarin. 

Benzo[6]thiophene aldehydes have been condensed with a variety of active methylene compounds, including cyclic511, 644 and open-chain645-647 ketones, aliphatic aldehydes,90 benzyl cyanides,93-436 malononitrile,487 rhodanine,144,648 hippuric acid,477 barbituric acid,487 diethyl malonate,487 and malonic acid (Section VI,M). Aliphatic nitro compounds condense smoothly with most benzo[6]-thiophene aldehydes03,141,337,343, 556,640,650 (except 5-hydroxy- and... 

The benzylic free radical produced by the addition of the carbamoyl radical to the ethyl cinnamate molecule is more stable than the alternative radical alpha to the ester group. With such an orientation of addition to the a,p-unsaturated ester, this reaction should lead to derivatives of malonic acid. However, it has been found that the intermediate radical, being a stable benzylic free radical, fails to perform the subsequent abstraction of a hydrogen atom from formamide, and thus no chain-transfer step takes place. Instead of performing this step it favours the combination with a semi-pinacol radical, which is present in solution, to yield the hydroxy ester which subsequently lactonizes to give the major product of the reaction (67). 

In the reaction of the isatins 7 [154, 155], 54 [17, 154, 155], or 186 [155, 158, 159] with malonic acid in the presence of sodium acetate [155, 158] or in acetic acid [17, 154, 155, 159] the reaction products were 2-hydroxy-4-quinolinecarboxylic acids, which usually exist in the form of the 2-quinolone derivatives 187, as a result of decarboxylation of the initially formed dicarboxylic acids. Compound 187 with R = R1 = R2 = H and R3 = Me was patented as a plant growth regulator (Aureorysin) [158],... 

Hydroxy-propionic acid 1,3-Propanediol, acrylamide, acrylic acid, acrylonitrile, ethyl-3-hydroxypropionic acid, L-alanine, L-serine, malonic acid, propiolactone, poly(3-HP), poly(3-hydroxybutyric acid-co-3-hydroxypropionic acid) Polymers, fine chemicals Cao et al., 1999 Werpy and Petersen, 2004 Zhang etal., 2004 Patel etal., 2006... 

Apart from the diols examined so far there are other bis-O nucleophiles that also react with carbonyl compounds following the mechanisms discussed, as illustrated by Figure 9.21. The result is acetal analogs such as the compounds D (from hydroxy carboxylic acid A), E (from enol carboxylic acid wo-B) or F ( Meldrum s acid from malonic acid). Each of these acetal analogs is used as a reagent in organic synthesis. 

A more unusual starting material is 3 carbethoxy 4 hydroxy coumarin (obtained by reaction between salycylaldehyde and malonic acid) which undergoes decarboxylation when reacting with benzalacetone. 

Wang used reactive-extrusion polymerization with 2,5-di-methyl-2,5-di-t-bu-tylperoxy hexane to prepared a graft copolymer, (11), by free radically grafting polyethylene-glycol malonic acid onto the biodegradable substrate of poly((3-hydroxybutyrate-co- p-hydroxy valerate). 

The hydroxy acid, /rans-cyclopentanol-2-acetic acid (57%), is made by refluxing /rans-cyclopentanol-2-malonic acid for 10 minutes in pyridine solution. ... 

Ouino.xaline di-.Af-oxides are not formed in the reaction of benzofuroxan v/ith malonic acid or malonales however, benzofuroxan reacts smoothly with ethyl cyanoacetate in the presence of a strong base such as l,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) with the elimination of alcohol to give 3-hydroxyquinoxaline-2-carbonitrile 1,4-dioxide. According to spectroscopic studies, the tautomeric equilibrium is shifted towards l-hydroxy-2-oxo-l,2-dihydroquinoxalin-3-carbonitrile 4-oxide. 

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