Mandelic acid, substituted

Cefonicid (55) is synthesized conveniently by nucleophilic displacement of the C-3 acetoxy moiety of with the appropriately substituted tetrazole thiol (54).The mandelic acid amide C-7 side chain is reminiscent of cefamandole. 

Sze IS-Y, S Dagley (1987) Degradation of substituted mandelic acids by meta fission reactions. J Bacteriol 169 3833-3835. 

Although the reaction could proceed via intermediate 14 or 15, the authors favour a mechanism where the formation of 14 is rate-determining because the displacement of the acetate at Pb by carboxylate anions is known to be rapid. The large negative AS (—34 e.u./mol) observed for the oxidation reaction is consistent with formation of the pseudo-cyclic intermediate 14. Also, the small Hammett p value of 0.4 determined for a series of meta- and para-substituted mandelic acids indicates that there is very little charge development on the benzyl carbon in the transition state of the rate-determining step. This is also consistent with the proposed mechanism. 

Toniolo reported the carbonylation of aromatic aldehydes containing electron-donating substituents with a Pd/PPh3 catalyst system in the presence of HC1 to give phenylacetic acid derivatives [64]. No activity was observed in the absence of PPI13 or HC1, and high yields could be achieved with alkanols as solvent (e.g., EtOH). It is believed that the mechanism involves HC1 addition to the aldehyde, with the resultant chlorohydrin being subject to oxidative addition to Pd, CO insertion, and alcoholysis. Upon Cl -o- OR substitution with the formed mandelic acid derivative, a second carbonylation takes place,... 

Mandelic acid, ethyl esters of substituted, cy-cloamylose action on hydrolysis of, 23 233... 

Dixon [75] also investigated the use of unconventional carbon donors, such as the mandelic acid derivative 119 in the highly stereoselective addition to -substituted nitro-olefms. The Michael product 120 was formed smoothly and can be converted in simple one-step procedures to generate various chiral building blocks for syntheses (Scheme 26). 

The chiral diphenyl-substituted polyether-diesters (SS)-87 and (SS)-88 were obtained (127) in similar fashion from the appropriate (55)-diphenyl derivative of tetraethylene glycol synthesized stereospecifically from (5)-mandelic acid. 

The pyridine subcycle unit has been introduced into a wide range of 18-crown-6 derivatives. For example, reaction of 2,6-pyridinedicarbonyl chloride with the dimethyl substituted tetraethylene glycol (SS)-84, derived from (S)-lactic acid, afforded (126) the chiral macrocyclic polyether diester (5S)-184. A similar preparative approach (127) gave (SS)-185, where the source of the chirality is (5)-mandelic acid. 

This general method has been applied to the synthesis of a variety of alkyl-substituted mandelic acids.2... 

Various dehydrating agents—concentrated sulphuric acid, zinc chloride, phosphorus pentoxide—can be used. Sulphuric acid, although perhaps the most convenient, has the disadvantage that it tends to sulphonate the aromatic substances employed. At a low temperature, however, diphenylmethane can be obtained from benzyl alcohol and benzene. At 140° phosphorus pentoxide condenses benzene and diphenylcarbinol to triphenylmethane (see B., 7,1204). Not only substituted benzyl alcohols, but even mandelic acid can be brought within the scope of the reaction, while in place of benzefte its nitro, amino or phenolic derivatives may be used. 

The oxidation of a-hydroxy acids by hexamethylenetetramine-bromine (HABR) is first order with respect to each of the hydroxy acids and HABR. The oxidation of o -deuteriomandelic acid exhibited a kinetic isotope effect of kn/ko = 5.91 at 298 K. The rates of oxidation of the substituted mandelic acids show excellent correlation with Brown s er+ values with negative reaction constants. A mechanism involving transfer of a hydride ion from the acid to the oxidant has been postulated.128... 

The ease of replacement of halogen atoms attached to the oxazole ring by nucleophiles follows the order Hal-2 Hal-4 > Hal-5. Halogen-metal exchange of 4- or 5-bromooxazoles with butyllithium, followed by quenching with D20, affords the corresponding deuterated oxazoles, but other replacement reactions are difficult. The 4-bromooxazole (139) gives a low yield of mandelic acid on alkaline hydrolysis (equation 6). The substitution of all three chlorine atoms in (140) by piperidine has been observed. 

In contrast to benzyl alcohol, a-substituted benzyl alcohols, benzyl ethers, and aryl ketones may be successfully hydrogenated over rhodium and rhodium-platinum catalysts to give the corresponding saturated products in high yields, as shown in eqs. 11.38-11.41. In the hydrogenations shown in eqs. 11.38 and 11.39, no racemization took place D-mandelic acid afforded D-hexahydromandelic acid in 94% yield and meso- and dl-2,3-dicyclohexyl-2,3-butanediol were obtained in 93 and 94% yields, respectively, by hydrogenation of the corresponding diphenyl compounds. 

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