Glycidic acids

Glycidic acids (which are isomeric with oc-oxo acids) can also be cleaved to an aldehyde and carbon dioxide either thermally or by the action of acids  

Since glycidic esters can usually be prepared from carbonyl compounds and chloroacetic esters, hydrolysis of the ester group and decarboxylation of the resulting glycidic acid gives as end-product the aldehyde containing one carbon atom more than those in the aldehyde or ketone  

Conversion of the glycidic ester into the aldehyde is usually performed in two steps the ester is first hydrolysed by aqueous or alcoholic alkali, and the glycidic acid is then cleaved by heating with dilute hydrochloric acid or thermally in a vacuum in the presence of copper or copper chromite. 

2-PhenylpropIonaldehyde 43 Ethyl methylphenylglycidate,44 which is readily obtained from acetophenone and ethyl chloroacetate, is hydrolysed by sodium ethoxide. The resulting sodium methylphenylglycidate solution is then added to dilute hydrochloric acid, and the whole is warmed cautiously. Carbon dioxide is evolved and the aldehyde is precipitated. 

A variation that is preparatively useful is to treat a glycidic acid with pyridine tribromide and semicarbazide, which on decarboxylation leads to the %,/ -unsaturated aldehyde.45 

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Instead of a-halo esters, related reactants can be used e.g. the a-halo derivatives of ketones, nitriles, sulfones and A,A-disubstituted amides. The Darzens condensation is also of some importance as a synthetic method because a glycidic acid can be converted into the next higher homolog of the original aldehyde, or into a branched aldehyde (e.g. 5) if the original carbonyl substrate was a ketone ... 

PHENYLMETHYLGLYCIDIC ESTER (Glycidic acid, (3-methyl-(J-phenyl-, ethyl ester)... 

Several microbial alcohol oxidoreductases can catalyze the stereoselective oxidation of GLD. Quinohaemoprotein ethanol dehydrogenase of Acetobacter pasteurianus is able to oxidize stereospecifically (S)-GLD to (l )-glycidic acid in racemic GLD [41,42 ]. When washed cells of A. pasteurianus were incubated with 4.8 mg ml" of racemic GLD, (1 )-GLD was obtained, with an optical purity of 99.5% e. e. and 64% conversion. 

An example of an industrial membrane bioreactor is the hollow-fiber membrane system for the production of (-)-MPGM (3-(4-methoxyphenyl)glycidic acid methyl ester), which is an important intermediate for the production of diltiazem hydrochloride [81, 82]. For the enantiospecific hydrolysis of MPGM a hollow-fiber ultrafiltration membrane with immobilized lipase from Serratia marcescens is used. (-f)-MPGM is selectively converted into (2S,3J )-(-F)-3-(4-methoxyphenyl)glyci-dic acid and methanol. The reactant is dissolved in toluene, whereas the hydrophilic product is removed via the aqueous phase at the permeate side of the membrane, see Fig. 13.9. EnantiomericaUy pure (-)-MPGM is obtained from the to-... 

The ring opening of glycidic acids and their derivatives by reactants such as the sodium salt of malonic ester has been reviewed in Russian. ... 

MPGM=/)-methoxyphenyl-glycidic acid methyl ester... 

The c 5-23-dimethylchionian-4-one 53 is obtained with fair enantioselectivity through an asymmetric Michael addition in the presence of (-)-quinine (Scheme 32) <99TL3777>. Directed metallation of protected phenols and subsequent reaction of the li derivative with enantiopure Weinreb amides of glycidic acids feature in a route to stereoisomers of 2-alkyl-3-hydroxychroman-4-ones (Scheme 33) <99JOC3489>. 

Epoxides (see also a,(3-Epoxy alcohols, etc., Glycidic acids, esters, nitriles) From alkenes by epoxidation Dimethyldioxirane, 120 Fluorine-Acetonitrile, 135 Potassium peroxomonosulfate, 259 From carbonyl compounds Alumina, 14... 

There are many pharmaceutical applications for the modification of one enantiomer over another, and to this end, many have studied these selective reactions in carbon dioxide. Glowacz et al. (1996) studied the enzymatic hydrolysis of triolein and its partial glycerides and found that stereoselectivity depends on reaction time and enzyme water content. They suggest that the water content varies the local environment of the enzyme in carbon dioxide and changes the local pH value. Rantakyla et al. (1996) also found that the hydrolysis of one stereoisomer over another was water-dependent. They studied the hydrolysis of 3-(4-methoxyphenyl)glycidic acid methylester and found that the 2S,3R enantiomer hydrolyzed more than fivefold faster than the 2R3S form. 

Methyl-3-phenyl glycidic acid ethyl ester... 

This knowledge was applied for even more complicated, bifunctional compounds such as phenyl glycidic acid methyl ester 3 to yield alpha-ketone carboxylic acid esters 4 such as 3-phenylpyroracemic acid methylesters (Eq. 15.2.2). 

Equation 15.2.2 Glycidic acid ester 3 to carboxylic acid ester 4... 

Fig. 15.2 Catalyst screening for the conversion of phenyl glycidic acid methyl ester to 3-phenylpyroracemic acid methylester...

By increasing the temperature over > 300°C, the phenyl glycidic acid esters are converted to phenyl acid esters. That occurs in a consecutive decarbonylation of a-ketone carboxylic acid esters as intermediate. In the case of p-tert-butyl glycidic acid ester in the presence of a boron-pentasil zeolite at 350 °C the ratio between a-ketone carboxylic acid ester and the phenyl acetic acid ester is 65 35. 

Steam distillation of the glycidic acid (98)178,183 proceeds with elimination of water and carbon dioxide to give 3-formylanthranil (anthroxanaldehyde, 99).183... 

Gabriel reaction, 679 Gattermann-Koch reaction, 280 Gattermann reaction, 94, 280 Glycerides, preparation, 481, 482 Glycidamides, preparation, 570 Glycidic acids, decarboxylation, 295 pyrolysis, 348... 

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