Oxidative decarboxylation with alkaline

Several total syntheses of antirhine (11) and 18,19-dihydroantirhine (14) have been developed during the last decade. Wenkert et al. (136) employed a facile route to ( )-18,19-dihydroantirhine, using lactone 196 as a key building block. Base-catalyzed condensation of methyl 4-methylnicotinate (193) with methyl oxalate, followed by hydrolysis, oxidative decarboxylation with alkaline hydrogen peroxide, and final esterification, resulted in methyl 4-(methoxycar-bonylmethyl)nicotinate (194). Condensation of 194 with acetaldehyde and subsequent reduction afforded nicotinic ester derivative 195, which was reduced with lithium aluminum hydride, and the diol product obtained was oxidized with manganese dioxide to yield the desired lactone 196. Alkylation of 196 with tryptophyl bromide (197) resulted in a pyridinium salt whose catalytic reduction... 

One synthesis of cyclopentenone [80], requiring a resolution, involved initial ring contraction of phenol when treated with alkaline hypochlorite (49). Resolution of the resulting cis acid [85] was effected with brucine. The desired enantiomer [86] formed the more soluble brucine salt and was thus obtained from the mother liquors of the initial resolution. Oxidative decarboxylation with lead tetracetate, partial dechlorination with chro-mous chloride, and alcohol protection gave chloro enone [87]. Zinc-silver couple (50) dechlorinated [87] to the desired cyclopentenone [80]. 

At alkaline conditions (pH=l 1) no phenol, hydroquinone were detected. This is possibly due to the fact that the rate of phenol oxidation increases under alkaline conditions with optimum pH between 9.5 and 13 [17] and so once it is formed, it is readily oxidised. The absence of phenol and increased concentration of p-hydroxybenzoic acid could be also explained by reduced decarboxylation rates under conditions of high pH, which would result in the oxidation of p-hydroxybenzaldehyde to form p-hydroxybenzoic acid. 

Ruthenium(III) catalyses the oxidative decarboxylation of butanoic and 2-methylpropanoic acid in aqueous sulfuric acid. ° Studies of alkaline earth (Ba, Sr) metal alkoxides in amide ethanolysis and of alkali metal alkoxide clusters as highly effective transesterification catalysts were covered earlier. Kinetic studies of the ethanolysis of 5-nitroquinol-8-yl benzoate (228) in the presence of lithium, sodium, or potassium ethoxide revealed that the highest catalytic activity is observed with Na+.iio... 

In this process, cumene is oxidized to cumene hydroperoxide by air at about 100°C in an alkaline environment. The oxidation products are separated, and the bottoms are mixed with a small amount of acetone and sulfuric acid and held at 70-80°C while the hydroperoxide splits into phenol and acetone. Total domestic phenol capacity with this process is about 4.8 billion lb/year. In the much smaller-volume benzoic acid process, toluene is air-oxidized to benzoic acid with a cobalt catalyst. The benzoic acid then is converted to phenol by an oxidative decarboxylation reaction with air at about 240°C. 

Chiral 4-hydroxy-2-cyclopentenones. Both (R)- and (S)-4-hydroxy-2-cyclo-pentenones can be obtained from phenol. The first step is alkaline hypochlorite oxidation to the acid 1, which is resolved with brucine. Oxidative decarboxylation of 1 gives 2, which is partially dechlorinated and protected as the silyl ether (3). The last step to 4 is reduction with zinc-silver (S, 760) or zinc-copper. ... 

Oxidation of (co)-lupulone with alkaline peroxide gives rise to lupuloxinic acid (46 R = COOH) which is readily decarboxylated to lupulenol (46 R = H) but neither of these products has been found in hops or beer. However the related trione, dehydrolupulenol (47) has been reported to account for 15 % of the autoxidation products of the p-acids [42]. 

Although the mechanisms of the oxidations of organic mono- and di-carboxylic acids have been much examined under acidic conditions, the faster reactions in alkaline media have only recently been investigated. In contrast to the reaction in acidic solution where, with mandelic acid as substrate, oxidative decarboxylation occurs to yield benzaldehyde and CO2, at the higher pH the product is phenylglyoxylic acid ... 

Care must also be taken, when solvent extraction is used, to avoid artefacts either from impurities in the solvent themselves (Perry and Hansen, 1974) or by the extraction of some of the non-acidic and neutral components of urine into the solvents at acid pH. These latter components include urea, phenols and alcohols, particularly those derived from dietary sources. To avoid this problem prior extraction of the urine with the same solvent systems at alkaline pH before subsequent acidification and re-extraction can be effective (Mamer et al, 1971), while the first step towards exclusion of artefacts requires the use of high-purity reagents and solvents. Although seldom incorporated into the solvent extraction methods that have been described, the prior stabilization of 0X0 acids as substituted oxime derivatives is also essential to avoid artefact formation during solvent extraction, such as the oxidative decarboxylation of phenylpyruvic acid to phenylacetic acid (Thompson etal., 1975). 

To complete the section on the synthesis of 4,4 -bipyridines, we summarize the methods reported for the preparation of some substituted 4,4 -bi-pyridines and 4,4 -bipyridinones. These methods are closely analogous to syntheses already discussed for some of the isomeric bipyridines. Thus the Hantzsch reaction using pyridine-4-aldehyde, ethyl acetoacetate, and ammonia gives 3,5-di(ethoxycarbonyl)-1,4-dihydro-2,6-dimethyl-4,4 -bipyridine, which after oxidation, followed by hydrolysis and decarboxylation, afforded 2,6-dimethyl-4,4 -bipyridine. Several related condensations have been reported. Similarly, pyridine-4-aldehyde and excess acetophenone gave l,5-diphenyl-3-(4-pyridyl)pentane-l,5-dione, which with ammonium acetate afforded 2,6-diphenyl-4,4 -bipyridine. Alternatively, 1-phenyl-3-(4-pyridyl)prop-2-enone, A-phenacylpyridinium bromide, and ammonium acetate gave the same diphenyl-4,4 -bipyridine, and extensions of this synthesis have been discribed. Condensation of pyridine-4-aldehyde with malononitrile in the presence of an alcohol and alkaline catalyst produced compounds such as whereas condensations of... 

From Catechol. Several routes have recently been developed for the synthesis of heliotropin from catechol. In one such route, catechol is converted into 3,4-dihydroxymandelic acid with glyoxylic acid in an alkaline medium in the presence of aluminum oxide. 3,4-Dihydroxymandelic acid is oxidized to the corresponding keto acid (e.g. with copper-(II) oxide), which is decarboxylated to 3,4-dihydroxybenzaldehyde [176]. The latter product is converted into heliotropin, for example, by reaction with methylene chloride in the presence of quaternary ammonium salts [177]. 

Pyrazinecarboxylic acid has been obtained by selenious acid oxidation in pyridine of methylpyrazine or aqueous permanganate oxidation of ethylpyrazine, in yields of 64 and 48%, respectively.171,218 It has also been obtained in 70% yield by partial decarboxylation of pyrazine-2,3-dicarboxylic acid on heating in vacuo at 210°.219 Aqueous permanganate oxidation of 2,5-distyrylpyrazine gives the 2,5-dicarboxylic acid.220 Pyrazine-2,5-dicarboxylic acid has also been prepared in 45% yield by direct carboxylation of pyrazine with carbon dioxide at 50 atm pressure at 250° for 3 hours in the presence of a potassium carbonate and calcium fluoride catalyst.221 Pyrazine-tricarboxylic acid (57), obtainable in only very poor yields by oxidation of 2,5-dimethyl-3-ethylpyrazine, is prepared in 87% yield by alkaline permanganate oxidation of 2-(D-arabo)tetrahydroxybutyl-quinoxaline (56).222 Decarboxylation of the tricarboxylic acid by... 

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