Phenyl acetic acids

Phenyl Acetic Acid, CeHs—CH2—COOH, Carboigr-methyl Benzene 

This acid is the simplest aromatic acid with the carboxyl in the side chain. Its name, phenyl acetic acid, indicates the relation to the aliphatic acids as a phenyl derivative. The commonly used names for the side-chain carboxy acids are derived similarly, e.g. phenyl propiolic acid. It will be seen at once that phenyl acetic acid and the toluic acids are isomeric, the first being the result of the partial oxidation of ethyl benzene, the latter the result of the partial oxidation of the di-methyl benzenes or xylenes which are isomeric with ethyl benzene. In both cases the relationship to the hydrocarbon is that only one carbon group of the side chain is oxidized to carboxyl. 

On further oxidation to the final product all the carbon groups of the side chain are completely oxidized and the products are as above, the dimethyl benzenes and toluic acids yielding di-carhoxyl ring acids while ethyl benzene and phenyl acetic acid yield the mono-carboxyl ring acid. This realtionship shows clearly the difference in character between a ring carboxyl acid and an isomeric side-chain carboxyl acid. Because of its isomerism with toluic acid phenyl acetic acid is also known as alpha-toluic acid, a name that does not seem advisable. While phenyl acetic acid is not of especial importance, the other side-chain carboxyl acids which we shall mention are of considerable importance. 

Now hydrocinnamic acid bears exactly the same relationship to cinnamic acid, the former being phenyl propionic acid, the latter phenyl acrylic acid. 

Hydrocinnamic acid beta-Phenyl propionic acid 

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It is suitable, not only for rose odours, but also for blending with almost any flower oil. Phenyl-ethyl alcohol forms a solid compound with chloride of calcium, which is very useful for its purification. On oxidation it is converted into a mixture of phenyl-acetaldehyde and phenyl-acetic acid. The last-named body forms an ethyl ester melting at 28°, which serves for its identification. 

Methyl Phenyl-acetate. — Phenyl-acetic acid can be prepared by... 

Shuric acid, yields phenyl-acetic acid or a-toluic acid. This is con-ansed with methyl alcohol, forming the methyl ester of the formula. COOCH3. It has a powerful honey odour, and is very useful in scent bases of this type. 

Benzyl cyanide, C Hj. CH.,CN, or phenyl-aceto-nitrile, is a constituent of cress oil, and probably of neroli oil. It is a strong smelling liquid boiling at 231 5°, and having a specific gravity 1 0146 at 18°. On boiling with alcoholic potash it yields phenyl-acetic acid, which can be identified by its melting-point, 77°, and by the analysis of its silver salt. 

This acid, CgHj. CH COOH, is a sweet-smelling substance, especially recommended for sweetening soap perfumes. It occurs in neroli oil, and has a sweet honey-like odour. It is formed by converting toluene into benzyl chloride which is converted into benzyl cyanide, which is digested with dilute sulphuric acid, and so converted into phenyl-acetic acid. It is a crystalline body, melting at 76° to 76 5° and Iwiling at 266°. It has been isolated from oil of neroli. 

D(-)-Oi-[ (Imidazolidin-2-on-1-yl)carbonylamino] phenyl Acetic Acid 6-Aminopenicillanlc Acid... 

To a solution of 4 g of sodium in 200 ml of n-propanol is added 39 g of homovanillic acid-n-propyl ester (boiling point 160°C to 162°C/4 mm Hg) and the mixture is concentrated by evaporation under vacuum. After dissolving the residue in 200 ml of dimethylformamide and the addition of 0.5 gof sodium iodide, 26.2 g of chloracetic acid-N,N-diethylamide are added drop-wise with stirring at an internal temperature of 130°C, and the mixture is further heated at 130°C for three hours. From the cooled reaction mixture the precipitated salts are removed by filtering off with suction. After driving off the dimethylformamide under vacuum, the product is fractionated under vacuum, and 44.3 g of 3-methoxy-4-N,N-diethylcarbamido-methoxy phenyl acetic acid-n-propyl ester are obtained as a yellowish oil of boiling point 210°C to 212°C/0,7 mm Hg,... 

Lumiracoxib, which has been approved in the UK but not by the FDA, has a phenyl acetic acid structure resembling diclofenac rather than the other coxibs... 

PHENYL ACETIC ACID SODIUM PHENYL ACETATE 4.3 3.5 to 5.1... 

The enantiomeric excess (ee) of the hydrogenated products was determined either by polarimetry, GLC equipped with a chiral column or H-NMR with a chiral shift reagent. Methyl lactate and methyl 3-hydroxybutanoate, obtained from 1 and 2, respectively, were analized polarimetry using a Perkin-Elmer 243B instrument. The reference values of [a]o(neat) were +8.4° for (R)-methyl pyruvate and -22.95° for methyl 3-hydroxybutcinoate. Before GLC analysis, i-butyl 5-hydroxyhexanoate, methyl 5-hydroxyhexanoate, and n-butyl 5-hydroxyhexanoate, obtained from 1, 5, and 6, respectively, were converted to the pentanoyl esters, methyl 3-hydroxybutanoate was converted to the acetyl ester, and methyl 4-methyl-3-hydroxybutanoate obtained from 2 was converted the ester of (+)-a-methyl-a-(trifluoromethyl)phenyl acetic acid (MTPA). 

If one of the species is anionic and we need to transport it to the organic phase, then a phase-transfer catalyst may be employed. Consider the example of benzyl penicillin where the reaction between phenyl acetic acid and the penicillin carboxylate ion, with penicillin amidase as a catalyst, is relevant, and which at pH 4.5 - 5.0 is shifted in the desired direction. Here a catalyst like tetrabutylammonium halide works, and with chloroform as a solvent 60% yield can be realized in contrast to a yield of only 5 - 10 % in water. 

Log-log plot of ionization constants of benzoic and phenyl-acetic acids in water at 25°. (From Physical Organic Chemistry by J. S. Hine. Copyright 1962. Used with permission of McGraw-Hill Book Company.)... 

The reaction of potassium 3-amino-4-oxo-3,4-dihydroquinazoline-2-thiolate 62 with a-bromophenylacetic acid 63 resulted in the formation of (3-amino-4-oxo-3,4-dihydroquinazolin-2-ylsulfanyl)-phenyl-acetic acid methyl ester 64 which on alkali treatment and subsequent acidification resulted in the synthesis of 2-phenyl- 1-thia-4,4a,9-triaza-anthracene-3,10-dione 65 <1999JCR(S)86>. Similarly, the reaction of potassium 3-amino-5,6-dimethyl-4-oxo-3,4,4a,7a-tetrahydrothieno[2,3- pyrimidine-2-thiolate 66 with a-bromo-ester 67 resulted in the formation of 2-(3-amino-5,6-dimethyl-4-oxo-3,4,4a,7a-tetrahydrothieno[2,3- / pyrimidin-2-ylsulfanyl)-propionic acid ethyl ester 68. Subsequent treatment with alkali followed by acidification resulted in the formation of 2,3,7-trimethyl-3a,9a-dihydro-l,8-dithia-4a,5,9-triazacyclopenta[ ]naphthalene-4,6-dione 69 <2000JHC1161>... 

The remarkably versatile Ci building block HCN may be used in the aqueous two-phased hydrocyanation, too (Equation 5.3 [37]). Also, some fine chemicals such as intermediates for vitamins, phenyl acetic acid, etc. are manufactured on an industrial scale using this technology (Equations 5.4 and 5.5 [12e,31b,38]). 

Davies, I.D., Allanson, J.P., and Causon, R.C. 1999. Rapid determination of the anti-cancer drug chlorambucil (Leukeran) and its phenyl acetic acid mustard metabolite in human serum and plasma by automated solid-phase extraction and liquid chromatography-tandem mass spectrometry. J. Chrom-matogr. B. 732 173. 

The reactive anion can also combine with some other saturated species as in the following example of phenyl acetic acid ... 

Defensive Compounds. The sweetish smell of Noterus species is due to the presence of phenyl acetic acid 14 as the main constituent of the pygidial gland secretion. Furthermore, some additional aromatics and 3-indole acetic acid 30 could be identified [82,104]. 

On the other hand, the organic acid and polymer (molecular weight varied from 2000 to 90,000) created no observable solubility enhancement. The investigation of phenyl acetic acid as a cosolute, with concentration > 600 mg/1, shows a slight enhancement for the most hydrophobic DDT. The magnitude of the DDT solubility enhancement/unit mass [19, 249] for phenylacetic acid was much smaller than with the DHA or DFA. They found that the solubility enhancement... 

Cleavage to 2-phenyl-ethylamine, phenyl-acetaldehyde and phenyl-acetic acid N-acetylation... 

Fenclofenac Fenclofenac, o-[2,4-dichlorophenoxy)phenyl]acetic acid (3.2.45), is synthesized from 2,4-dichlorophenol and 2-chloroacetophenone, the reaction of which in the presence of sodinm hydroxide and powdered copper forms the corresponding 2-acetyl-2, 4 -dichloro-diphenyl ester (3.2.43). The resulting product is reacted with sulfur and morpholine according to Willgerodt method, giving thioamide (3.2.44), which is further hydrolyzed to the desired fenclofenac [109,110]. 

Cohare and co-workers reported that aristolactam BU (22) was prepared, following Kupchen s method, by Perkin condensation of 6-bromo-3,4-di-methoxy phenyl acetic acid (119) and o-nitrobenzaldehyde (120) (Scheme 14). The 2-bromo-4,5-dimethoxy-2 -nitro-ds-stilbene-a-carboxylic acid (121) was obtained. The nitro group of 121 was reduced with ferrous sulfate and ammonium hydroxide, and the resulting 2-bromo-4,5-dimethoxy-2 -amino-cw-stilbene-a-carboxylic acid (122) without purification was submitted to the Pschorr phenanthrene synthesis to yield l-bromo-3,4-dimethoxyphen-anthrene-lO-carboxylic acid (123). The phenanthrylamine 124 was prepared from 123 via a Schmidt reaction, and, by treatment with n-butyllithium and CO2, 124, afforded 22 (42). 

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