Phenylacetic acid reduction

This procedure is an adaption of one described by Hauser and Chambers. Previous preparations include the benzylation of diethyl phenylmalonate followed by hydrolysis, the benzylation of phenylacetonitrile followed by hydrolysis, the benzylation of phenylacetic acid through the Ivanov reagent, and the reduction of oi-phenylcinnamic acid using sodium amalgam. ... 

Inclusion of basic nitrogen in the p-position is also compatible with antiinflammatory activity in this series. Nitration of phenylacetic acid (27) affords 28. Methyl iodide alkylation of the enolate prepared from 28 using two equivalents of sodium hydride gives 29. This appears to involve an Ivanov intermediate (28a). Catalytic reduction of the... 

Base-catalyzed condensation between phenylacetic acid and phthalic acid produces enol lactone 78, which is reduced to benzoate 79 with HI and phosphorous. Friedel-Crafts cyclization by polyphosphoric acid followed by reduction produces alcohol 80. This alcohol forms ethers exceedingly easily, probably via the carbonium ion. Treatment with N-methyl-4— piperidinol in the presence 6f acid leads to the antidepressant hepzidine (81). 

Robinson et al. [263] have studied both at the laboratory and semi-technical scale the electrochemical generation of chromous ion (Cr(II)) for the reduction of sodium hydroxymandelate (SHM) to 4-hydroxy phenylacetic acid (HPA), a Tenormin intermediate, as a potential replacement for the existing Zn(Hg) reduction process. 

Diclofenac Diclofenac, 2-[(2,6-dichlorophenyl)-amino]-phenylacetic acid (3.2.42), is synthesized from 2-chIorobenzoic acid and 2,6-dichloroaniline. The reaction of these in the presence of sodium hydroxide and copper gives iV-(2,6-dichlorophenyl)anthranyIic acid (3.2.38), the carboxylic group of which undergoes reduction by lithium aluminum hydride. The resulting 2-[(2,6-dicholorphenyl)-amino]-benzyl alcohol (3.2.39) undergoes further chlorination by thionyl chloride into 2-[(2,6-dichlorophenyl)-amino]-ben-zylchloride (3.2.40) and further, upon reaction with sodium cyanide converts into... 

Methylcryptaustoline iodide (14) was synthesized from phenylacetic acid 47 by Elliott (39) as shown in Scheme 7. Nitration of 47 to the 6-nitro compound 48 and reduction with sodium borohydride afforded lactone 49. Reduction of the aromatic nitro group with iron powder in acetic acid gave ami-nolactone 50, which was converted to tetracyclic lactam 51 with trifluoroacetic acid in dichloromethane. Reduction of the lactam by a borane-THF complex followed by treatment with methyl iodide afforded ( )-0-methylcryptaustoline iodide (14). 

The known pyruvic acid 87 [Fig. (25)] [54] was oxidatively decarboxylated [55] to afford the phenylacetic acid 88, which was reductively cyclized to give the required oxindole 89 in nearly quantitative yield. 

Desoxybenzoin has been prepared by treatment of bromo-stilbene with water in a sealed tube at 180-190° 1 by the reduction of benzoin 2 by the reduction of benzil 3 by the action of zinc and alcoholic hydrogen chloride on chlorobenzil 4 by the action of benzene on phenylacetic acid in the presence of phosphorus pentoxide 5 and by the action of benzene on phenylacetyl chloride in the presence of aluminum chloride.6... 

Reductive cyclization of o-nitrophenylacetic acids is a very general method of oxindole synthesis (see Section 3.06.2.1.1 for the application of this method to indoles in general). The main problem is efficient construction of the desired phenylacetic acid. One method involves base-catalyzed condensation of substituted nitrotoluenes with diethyl oxalate followed by oxidation of the 3-arylpyruvate (equation 200) (63CB253). Nucleophilic substitution of o-nitrophenyl trifluoromethanesulfonate esters, which are readily prepared from phenols, by dimethyl malonate provides another route (equation 201) (79TL2857). 

In analogy to the reduction of aliphatic halogen compounds, the reduction of sulfonates can be used for the alkylation of phenylacetic acids 435) ... 

Disposition in the Body. Readily absorbed after oral administration bioavailability about 65%. Haloperidol is localised in the tissues and rapidly taken up by the brain. It is slowly excreted in the urine, about 40% of a dose being eliminated in 5 days with only about 1% of the dose as unchanged drug about 15% of a dose is excreted in the bile. Metabolites which have been identified in urine are 4-fluorobenzoylpropionic acid and 4-fluorophenylaceturic acid (the glycine conjugate of 4-fluoro-phenylacetic acid), both of which are inactive. Haloperidol is also metabolised by reduction of the ketone group to a secondary alcohol. 

Enholm [13] has also described the synthesis of soluble designer supports by the ring-opening metathesis polymerization (ROMP) of norbornyl derivatives. Reduction of norbornene-l-carboxaldehyde 88 to the corresponding alcohol 89, followed by treatment with either 2-bromopropionic acid or 2-bromo-2-phenylacetic acid in the presence of DCC, provided the esters 90 or 91 respectively (Scheme 19). Polymerization of 90 and 91 was carried out with Grubbs catalyst and halted after 25 s by capping with excess ethyl vinyl ether to give polymers 92 and 93 respectively. 

The racemic 2,3-diphenylbutane-1,4-diol 8, can be prepared via oxidative coupling of phenylacetic acid esters using TiCVEtaN10 followed by NaBHt/k reduction.11 We have examined the resolution of this valuable racemic diol using B(OH)3 and S-proline. The results are outlined in Scheme 4.llb... 

In the Pschorr synthesis (Scheme 12.12), a Perkin reaction (see Chapter 6) between 2-nitrobenzaldehyde and sodium phenylacetate in the presence of acetic anhydride yields 3-(2-nitrophenyl)-2-phenyl-propenoic acid. Reduction of the nitro group and deamination of the resulting amine via its diazonium salt (see Chapter 8) is accompanied by cyclization. Thermal decarboxylation completes the sequence. 

Phenylacetic Acid (Coll. Vol. i, 427) Prepared by catalytic reduction of mandelic acid. Zelinsky, Paceendobi e, and Leder-Packendoeef, Ber. 67, 300... 

Acyl radicals and acyl anions are proposed intermediates in the reduction of phenylacetyl chloride and hydrocinnamoyl chloride at mercury in MeCN [223]. Among the products obtained from the reduction of phenylacetyl chloride are 1,4-diphenyl-2-butene-2,3-diol diphenylacetate, phenylacetaldehyde, toluene, 1,3-diphenyl-acetone, and l,4-diphenyl-2,3-butanediol, as well as phenylacetic acid and phenylacetic acid anhydride. Analogous products arise from the reduction of hydrocinnamoyl chloride l,6-diphenyl-3-hexene-3,4-diol dihydrocinnamate, hydrocinnamaldehyde, ethyl benzene, l,6-diphenyl-3,4-hexanediol, hydrocinnamic acid, and hydrocinnamic acid anhydride. 

Aliphatic carboxylic acids are reducible to the alcohol in low yield in strongly acidic electrolytes. Thus, phenylacetic acid is reduced to 2-phenylethanol in 25-50% yield at a lead cathode in 50% sulfuric acid-ethanol [39] and butyric acid to butanol in 80% sulfuric acid in 6.5% yield [40]. The latter conversion can also be performed in 17% yield in 7% aqueous sodium hydroxide, despite the fact that the carboxylate form of the acid, which is reducible only with difficulty, predominates in bulk solution, suggesting an electrocatalytic reduction involving specific interaction of the substrate and electrode surface. 

Reduction of benzyl halides by Na(Hg) in propylene carbonate in the presence of CO2 gave the Na salt of the corresponding phenylacetic acid [68]. 

A synthetic route to ( )-0,f>-dimethyltubocurarine iodide (CXXV), via the racemate of 0,0-dimethylbebeerine (CXXIII), was announced in 1959 by Tolkachev and his collaborators (94). It started by the condensation of 3-methoxy-4-hydroxyphenethylamine with 4-benzyloxy-phenylacetic acid to give the amide CXXVI. Reaction of the potassium salt of the latter with the methyl ester of 3-bromo-4-methoxyphenyl-acetic acid in the presence of copper powder gave compound CXXVII. This on condensation with 3-methoxy-4-hydroxy-5-bromophenethyl-amine afforded compound CXXVIII, which was methylated to CXXIX. The latter compound was cyclized with phosphorous oxychloride to the dihydroisoquinoline derivative CXXX. Debenzylation of CXXX followed by intramolecular Ullmann condensation yielded compound CXXXI. The latter was converted to racemic dimethylbebeerine (CXXIII) by reduction with zinc dust in acetic acid followed by methyla-tion. Finally, treatment of ( + )-CXXIII with methyl iodide furnished the dimethyl ether of ( + )-tubocurarine iodide, identified by comparison of its UV-spectrum with that of the dimethyl ether of natural tubo-curarine iodide and by melting-point determination of a mixture of the two specimens. 

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