Phenylacetate 2-hydroxylation

Monoprotection of a symmetrical diol can be effected by reaction with a polymer-supported phenylacetyl chloride. The free hydroxyl group is then converted to an ether and the phenylacetate cleaved by aqueous ammonia-dioxane, 48 h. ... 

The taxonomic application of the ability of enteric organisms to grow with 4-hydroxy-phenylacetate (Cooper and Skinner 1980) and 3-hydroxyphenylpropionic acid (Burlingame and Chapman 1983) has been established. In addition, it has been demonstrated that the enzyme that carries out the hydroxylation has a wide substrate range extending to 4-meth-ylphenol, and even to 4-chlorophenol (Prieto and Garcis 1994). 

In Pseudomonas putida, the hydroxylation of 4-hydroxyphenylacetate to 3,4-dihydroxy-phenylacetate is carried out by an enzyme that consists of a flavoprotein and a coupling factor (Arunachalam et al. 1992). At least in Escherichia coli, it has been suggested that the large component is an FADH2-utilizing monooxygenase (Xun and Sandvik 2000 Chaiyen et al. 2001). 

Dopamine metabolism was covered in the discussion of general catecholamine biochemistry. Dopamine is stored in synaptic vesicles, and this storage can be manipulated. Although the reuptake of released DA is the major deactivating mechanism, MAO and COMT act enzymatically on DA in the same way as on NE. However, following the degradative pathway of NE, DA will finally be metabolized to homovanillic acid (3-methoxy-4-hydroxy-phenylacetic acid), since it lacks the P-hydroxyl group. 

Ultraviolet irradiation of CCXLV, which is obtained by the condensation of diphenylketene and diphenyldiazomethane, in hydroxylic solvents, effects its cleavage into the starting materials in the presence of carboxylic acids or alcohols, photoaddition takes place with the formation of benzilic acid derivatives.167 On the other hand, irradiation of CCXLV in benzene containing acetic acid and/or methanol produces CCXLVI and CCXLVII, respectively. Irradiation in the presence of diphenylmethane under nitrogen atmosphere yields phenylacetic acid. 

There has been a short review of the oxidative nucleophilic substitution of hydrogen in nitroarenes in which recent results with carbon, nitrogen, and oxygen nucleophiles are summarized and the preferred oxidants are discussed.11 The oxidative substitution of nitroarenes with carbanions of isopropyl phenylacetate in liquid ammonia-KMn04 initially yields products (4) which may suffer hydroxylation at the o -position, and dimeric and trimeric products may be formed by couplings of nitrobenzylic radicals formed during the reaction.12... 

The allyl group in the allylphenols can be oxidized, after protecting the hydroxyl group, to yield substituted phenylacetaldehydes 78 - 76 76 and phenylacetic acids. Thus, homogentisic acid LXIII is prepared readily by ozonizing the dibenzoate of allylhydroqumone LXIV, which is obtained by rearrangement of the allyl ether of hydroquinone mono-... 

Although significant improvements have been made in the synthesis of phenol from benzene, the practical utility of direct radical hydroxylation of substituted arenes remains very low. A mixture of ortho-, meta- and para-substituted phenols is typically formed. Alkyl substituents are subject to radical H-atom abstraction, giving benzyl alcohol, benzaldehyde, and benzoic acid in addition to the mixture of cresols. Hydroxylation of phenylacetic acid leads to decarboxylation and gives benzyl alcohol along with phenolic products [2], A mixture of naphthols is produced in radical oxidations of naphthalene, in addition to diols and hydroxyketones [19]. 

A reactor was charged with 3L water, 390 g of zinc powder (<63 jLm), 66 ml of 57% aqueous HI solution, stirred at ambient temperature 5 minutes, and 67.2 g of Cu(II)bromide dissolved in 260 ml water slowly added. Thereafter, a solution of 910.2 g scopolamine-2-hydroxyl-2-phenylacetate dissolved in 2.6 L water was slowly added, the pH adjusted to 4.5-5 with 227 ml 62% aqueous HBr, the mixture heated to 75-80°C 2 hours, cooled to... 

Disposition in the Body. Variably absorbed after oral or rectal administration and distributed into the synovial fluid. Metabolised by glucuronic acid conjugation, some conjugation with glycine, deallylation to form 3-chloro-4-hydroxyphenylacetic acid, and hydroxylation to form 3-chloro-4-(2,3-dihydroxypro-pyloxy)phenylacetic acid, which may be methylated an epoxide... 

Phenylacetic acid reacts to give, in very strongly acidic media (pH < 2), the benzyl radical, and, in less acidic media (pH > 2), adducts of the hydroxyl radical and benzene since there are three possible adducts the... 

OH group may be assumed to form the anion/molecule complex 139 which, however, is non-reactive with respect to further tautomerization. Rather, this complex loses the entire carboxylate residue as the fragment ion m/z 255), leaving the phenolic unit as a quinoid neutral fragment (Scheme 37) °. In a further work, 3,4-dihydroxybenzyl carboxylates derived from stearic acid (cf. 140), dihydrocinnamic acid and phenylacetic acid were studied under NC1(NH3)-MS/MS conditions. In these cases, deprotonation was found to take place exclusively at the phenolic sites, owing to the increased acidity of hydroxyl groups in a catechol nucleus, in contrast to simple phenols. Heterolysis of the benzylic C—O bond, e.g. in ions [140 — gives rise to reactive anion/molecule complexes,... 

Reduction. The reagent is useful for reduction of carboxylic acid esters to primary alcohols. For example, the following esters have been reduced to the corresponding carbinols ethyl p-nitrobenzoate (96% yield), ethyl phenylacetate (90% yield), ethyl gly-cinate (70% yield). The reaction has some useful features Hydroxylic solvents (ethanol, water) can be used, the selectivity is higher than in the case of lithium aluminum hydride, and the reagent is nearly neutral. The reagent was found to be satisfactory for reduction of the dimethyl ester of 4,4 -dinitro-2,2 -diphenic acid (la) to the corresponding alcohol (lb, 51%yield).2... 

It has been suggested that active transport systems for benzoate (Thayer and Wheelis 1982) and for mandelate (Higgins and Mandelstam 1972) are involved. In Rhizobium leguminosarum, 4-hydroxybenzoate hydroxylase activity is required for the uptake of 4-hydroxybenzoate (Wong et al. 1994), while in P. putida a gene cluster pcaRKF is involved in the transport of 4-hydroxybenzoate into the cells, their chemotactic response to the substrate and its degradation by ring hydroxylation (Harwood et al. 1994 Nichols and Harwood 1997). The situation for phenylacetate transport into P. putida U is... 

Rate constants for methanol and ethyl alcohol relative to those for benzoate ion, phenylacetate ion and p-nitrobenzoate ion are shown in Table III. Each value in the table consists of experiments at five separate concentration ratios. The random uncertainty in each value is less than 10%. In determining these rate constants from optical density ratios it was necessary to make a small correction for the contribution to the optical density by the H-adduct free radical. The molar extinction coefficients at 340-350 m/x for the H-adduct and OH-adduct are similar for benzoic acid (22) and were assumed to be comparable for the other two aromatic ions in the table. The correction is necessary since the rate constants for the reaction of hydrogen atoms with the alcohols used are two orders of magnitude lower than the rate constants for hydrogen atom addition to the aromatic ring, while the analogous hydroxyl rate constants are roughly comparable. 

---