Phenylacetic acid, bromination

Periodic acid dihydrate, with iodine and durene to give iododurene, 51, 94 Phenols, from aryl methyl ethers, 53, 93 Phenylacetaldehyde, from 2-lithio-1,3,5-trithiane and benzyl bromide, 51, 43 Phenylacetic acid, bromination, 50, 31... 

Since the mode of inhibition is competitive and the Kj value is extraordinarily small compared to the value of the substrate (25 mM), it is strongly suggested that this inhibitor blocks the active site and prevents approach of the substrate to the catalytic site of the enzyme. It is assumed that a-bromo-phenylacetic acid interacts with a cysteine residue at the active site in some way. The high electron-withdrawing effect of the bromine atom would have an important role in the inhibition mechanism. Thus, the mode of binding of the inhibitor to the active site of the enzyme is presumed to resemble that of the substrate closely. Accordingly, disclosure of the way the inhibitor interacts with the enzyme would provide important information on how the enzyme activates the substrate. 

Kennedy and Stock reported the first use of Oxone for many common oxidation reactions such as formation of benzoic acid from toluene and of benzaldehyde, of ben-zophenone from diphenyhnethane, of frawi-cyclohexanediol Ifom cyclohexene, of acetone from 2-propanol, of hydroquinone from phenol, of e-caprolactone from cyclohexanone, of pyrocatechol from salicylaldehyde, of p-dinitrosobenzene from p-phenylenediamine, of phenylacetic acid from 2-phenethylamine, of dodecylsulfonic acid from dodecyl mercaptan, of diphenyl sulfone from diphenyl sulfide, of triphenylphosphine oxide from triphenylphosphine, of iodoxy benzene from iodobenzene, of benzyl chloride from toluene using NaCl and Oxone and bromination of 2-octene using KBr and Oxone . Thus, they... 

In the original patent published by Merck in 1995, rofecoxib (2) was synthesized in three steps from the known 4-(methylthio)acetophenone (10), prepared from the Friedel-Crafts acylation of thioanisole. As depicted in Scheme 2, oxidation of sulfide 10 using an excess of magnesium monoperoxyphthalate hexahydrate (MMPP, an inexpensive, safe and commercially available surrogate for w-CPBA) gave rise to sulfone 11, which was subsequently brominated with bromine and AICI3 to afford 2-bromo-l-(4-(methylsulfonyl)phenyl)ethanone (12). After recrystallization from 1 1 EtOAc/hexane, the pure phenylacyl bromide 12 was then cyclo-condensed with phenylacetic acid under the influence of l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to deliver rofecoxib (2) in... 

The synthesis of rofecoxib can be achieved by several different routes (Drugs Fut., 1998). A highly efficient synthesis for rofecoxib was recently described (Therien et al., 2001). As illustrated in Scheme 79, acetophenon (i) is prepared according to the literature, by Friedel-Crafts acylation with thioanisole. Oxidation with MMPP (magnesium monoperoxyphthalate hexahydrate) affords the sulfone (ii), which is reacted with bromine in chloroform in the presence of a trace amount of AICI3, to give (iii). Bromoketone (iii) is than coupled and cyclized in a second step, one-pot procedure with phenylacetic acid. Firstly, the mixture of bromoacetophenone (iii) and phenylacetic acid in acetonitrile is treated with... 

The unsaturated nature of the monobasic acid, atropic acid, which results from the dehydration of tropic acid, is readily established by the ease with which it absorbs two atoms of bromine (14) or hydrogen (sodium amalgam) (18). From the oxidation of atropic acid to benzoic acid it may be characterized as an unsaturated Cg-monocarboxylic acid with one phenyl group as a substituent. Only two structures (II and III) account for these facts. The isolation of formic acid and phenylacetic acid from the alkaline... 

Rofecoxib is also accessible by a comparatively short synthesis. [206] The starting material, methyl phenyl sulfide, is converted by Friedel-Crafts acylation and oxidation into the required sulfonylacetophenone. This is brominated and finally condensed with phenylacetic acid to result in the active compound. 

Lithiation of the toluene (51) and carboxylation (CO2) gives the corresponding phenylacetic acids in excellent yield. This method is claimed to have a considerable advantage over the conventional procedure of benzylic bromination, cyanide displacement, and hydrolysis. 

Bromine and acetic acid added to a soln. of l-methylsulfinyl-l-methylthio-2-phenylethylene in acetic acid, and stirred 17.5 hrs. at room temp. a-bromo-phenylacetic acid. Y 73%. F. e. s. K. Ogura, S. Furukawa, and G. Tsuchihashi, Bull. Chem. Soc. Japan 48, 2219 (1975). 

Phenylacetic acids have been prepared from 2,2-dichlorostyrenes by sequential hydroboration and oxidation (Cr03-H2S04) of the intermediate trialkyl borane, and benzoyl benzoic acids (8), not readily available by other routes, have been obtained" in good yield by treatment of phthalic anhydride with aryl-lithiums at — lOO C. Syntheses of some bicyclo [1,1,0] butane-l-carboxylic acids (9) and a range of cyclopropane-1-carboxylic acids [(10) and (II)] have been described. 1-Hydroxy-cyclopropanecarboxylic acids (13) have been prepared from the hydroxy-cyclobutanone derivatives (12), following bromination and hydrolysis. 

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