4-Methoxymandelic acid

Baciocchi E, Gerini MF, Lanzalunga O et al (2002) Lignin peroxidase catalysed oxidation of 4-methoxymandelic acid. The role of mediator structure. Tetrahedron 58 8087-8093... 

C9H10O5 DL-3-hydroxy-4-methoxymandelic acid 3695-24-7 493.15 43.226 2 16927 C9H11N02 ethyl 2-aminobenzoate 87-25-2 541.15 47.852 1,2... 

Reaction of diclilorocarbene with substituted benzaldehydes affords the corresponding mandelic acids. It might be supposed that this reaction does not involve dichlorocarben but rather its precursor, the trichloromethide ion. Nucleophilic addition of the trichlorc methyl anion to benzaldehyde should yield phenyl trichloromethyl carbinol. In control experiments, however, phenyl trichloromethyl carbinol was not hydrolyzed to mandelic acid under the reaction conditions. It was suggested that the reaction involves dichlorocarbene addition to the benzaldehyde carbonyl to form 2,2-dichloro-3-phenyloxirane followed by rearrangement to a-chlorophenylacetyl chloride which then is hydrolyzed as shown in equation 3.16. Mandelic, 4-methylmandelic, and 4-methoxymandelic acids were produced in 75%, 80%, and 80% yields, respectively [24]. 

Synonyms a,3-Dihydroxy-4-methoxybenseneacetic acid 3-hydroxy-4-methoxymandelic acid Trade names ... 

Disulfoton exposure altered catecholamine levels in animals, and this hormonal imbalance may be associated with elevated acetylcholine levels (Brzezinski 1969, 1972, 1973 Brzezinski and Ludwicki 1973 Brzezinski and Rusiecki 1970 Wysocka-Paruszewska 1970, 1971). In these studies, acute dosing with disulfoton caused increases in urinary and plasma noradrenaline and adrenaline levels, accompanied by decreases of adrenaline in the adrenal glands, in rats. In addition, the major urinary metabolite of catecholamine metabolism, 4-hydroxy-3-methoxymandelic acid (HMMA), was recovered in the urine from rats given acute doses of disulfoton (Wysocka-Paruszewska 1970,... 

Wysocka-Paruszewska B. 1970. Urine level of 4-hydroxy-3-methoxymandelic acid in urine of rats poisoned with phosphorus organic insecticides. Dissertationes Pharmaceuticae et Pharmacologicae 22 485-489. 

Disposition in the Body. Rapidly metabolised before reaching the systemic circulation and therefore ineffective after oral administration poorly absorbed after subcutaneous injection widely distributed throughout the body. The principal metabolic reaction is 0-methylation catalysed by catechol-O-methyltrans-ferase to form normetanephrine this is followed by oxidative deamination catalysed by monoamine oxidase, to form 4-hydroxy-3-methoxymandelic aldehyde which is converted to 4-hydroxy-3-methoxymandelic acid (vanillylmandelic acid) and to... 

Good results were obtained by oxidation of the /V-acylhydroxylamine derived from (/ )-methoxymandelic acid with the Swern reagent at — 78 "C in dichloromethane100. 

If the hydroxylic group next to the carboxyl is tertiary, decarboxylative oxidation gives ketones. Benzilic acid is degraded to benzophenone in 85-90% yield on refluxing for 20 min with water and iV-bromosuccinimide [745]. 2-(p-Methoxybenzyl)-p-methoxymandelic acid is converted into des-... 

Vanillin may also be prepared synthetically by condensation, in weak alkali, of a slight excess of guaiacol with glyoxylic acid at room temperature. The resultant alkaline solution, containing 4-hydroxy-3-methoxymandelic acid is oxidized in air, in the presence of a catalyst, and vanillin is obtained by acidification and simultaneous decarboxylation. Vanillin is then purified by successive recrystallizations. 

As shown in Table 5.4, the resolution efficiencies for the p-substituted 1-phenyl-efhylamine derivatives were greatly improved, as was expected, when p-methyl-and p-methoxymandelic acids were used in the place of mandelic acid. These results strongly support our explanation that two factors, hydrogen-bonding interaction to form a supramolecular sheet consisting of 2i-columns and van der Waals interaction between the sheets, govern the stability of diastereomeric salts [11]. The same factors were also found in the diastereomeric salts of racemic arylalka-noic acids with enantiopure amino alcohols [12]. 

To conclude, it is interesting to discuss in more detail the synthesis of vanillin from 4-hydroxy-3-methoxymandelic acid. According to scheme 1, glyoxylic acid reacts with guaiacol to give the substituted mandelic acid. 

Substitution in the ring occurred when 4-methoxyphenol, glyoxylic acid and alumina were added to 2M sodium hydroxide and the mixture was stirred at ambient temperature for 12 hours giving a 75% yield of 2-hydroxy-5-methoxymandelic acid which upon oxidation gave 2-hydroxy-5-methoxybenzaldehyde (ref.173). 

Li, Z. Ojala, W. Grant, D.J.W. Molecular modeling study of chiral drug crystals lattice energy calculations. J. Pharm. Sci. 2001, 90, 1523-1539. Kinbara, K. Saiko, K. Hashimoto, Y. Nohira, H. Saigo, K. Chiral discrimination upon crystallization of the diastereomeric salt of 1-aryethyl-amines with mandelic acid or /i-methoxymandelic acid interpretation of the resolution efficiencies on the basis of the crystal structures. J. Chem. Soc. Perkin Trans. 1996, 2, 2615-2622. 

BO = a-benzoinooxime BP = 2,2 -bipyridine BPH =/ /-benzoyl-/ /-phenylhydroxylamine CA = chloranilic acid DHN =2,3-dihydroxy-naphthalene DMG = dimethylglyoxime DTPA = diethylenetriaminepentaacetic acid HMMA = 4-hydroxy-2-methoxymandelic acid MA = mandelic acid NN = 1-Nitroso-2-naphthol PC = Pyrocatechol TC = 2 2 -Thiazolulazo)-p-crezol TTHA = triethylenetetramine-nehexaacetic acid. 

Gas Chromatographic Estimation of Urinary Homovanillic Acid and 4-Hydroxy-3-methoxymandelic Acid Using Capillary Columns Clin. Chim. Acta 55(1) 111-112 (1974)... 

Gas Chromatography in the Estimation of Urinary Metanephrines and VMA [4-Hydroxy-3-methoxymandelic Acid] Clin. Chim. Acta 32(3) 361-366 (1971) CA 75 45492b... 

McGregor, R. F., Khan, M., Marrack, D. and Sullivan, M., Quantitative analysis of 4-hydroxy-3-methoxymandelic acid by direct photometric scanning of urinary extracts separated by thin-layer chromatography. Am. J. Clin. Pathol. 46, 163 (1966). 

The diagnosis of neural tumours such as phaeochromocytoma and neuroblastoma is heavily dependent on the laboratory measurement of urinary levels of methylated catecholamines and of their two acidic catabolites, 4-hydroxy-3-methoxymandelic acid (VMA) and 4-hydroxy-3-methoxyphenyl acetic acid (HVA). 

The major metabolites resulting from these processes are the methylated derivatives metadrenaline and normetadrenaline, and 4-hydroxy, 3-methoxymandelic acid, (HMMA, VMA). 

See also adrenaline, 4-hydroxy, 3-methoxymandelic acid, phaeochromacytoma... 

HYDROXY, 3-METHOXYMANDELIC ACID (HMMA) (VANILLYL-MANDELIC ACID, VMA)... 

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