Acetophenones and phenylacetic acids

Phenones are C6-C2 compounds that are rarely found in nature. Examples include 2-hydroxyacetophenone (1.10) and 2-hydroxyphenyl acetic acid (1.11). 

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Acetophenones are aromatic ketones, and phenylacetic acids have a chain of acetic acid linked to benzene. Both have a C6-C2 structure. 

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... 

Adoption of a novel process for the manufacture of phenylacetamide and phenylacetic acid based on acetophenone this plant is perhaps the only one of its kind in the world... 

Considering the formation of C02" on CdS-DMF, we successfully applied the CdS-DMF photocatalysis to the fixation of CO2 into benzophenone (BP), acetophenone (AP), and benzyl halides (BnCl and BtiBr) (Table 1). Four substrates gave benzilic acid, atrolactic acid, and phenylacetic acid as respective fixation products, with dimerized and hydrogenated products. Considering the mechanism proposed above, C02 formed through the same route as described therein should participate in the fixation reaction. 

The ketones are readily prepared, for example, acetophenone from benzene, acetyl chloride (or acetic anhydride) and aluminium chloride by the Friedel and Crafts reaction ethyl benzyl ketones by passing a mixture of phenylacetic acid and propionic acid over thoria at 450° and n-propyl- p-phenylethylketone by circulating a mixture of hydrocinnamic acid and n-butyric acid over thoria (for further details, see under Aromatic Ketones, Sections IV,136, IV,137 and IV,141). 

Several pathways are used for the aerobic degradation of aromatic compounds with an oxygenated C2 or C3 side chain. These include acetophenones and reduced compounds that may be oxidized to acetophenones, and compounds including tropic acid, styrene, and phenylethylamine that can be metabolized to phenylacetate, which has already been discussed. 

A mixture of 0.33M of the acetophenone, 39 g of redistilled morpholine and 14.4 g sulfur is refluxed for 12 hours and the wrm solution poured into 175 ml hot ethanol. Cool to precipitate about 80% yield of the substituted phenylacetothiomorpholide (I). Mix about 50 g (I), 110 ml acetic acid, 16 ml sulfuric acid and 25 ml water and reflux 5 hours. Decant from the small amount of tar formed with stirring into 850 ml water. Filter, wash the precipitate with water and heat the precipitate with 225 ml 5% aqueous NaOH. Filter and acidify the filtrate with dilute HCI to give about 80% yield of the substituted phenylacetic acid (II). Mix about 21 g (II) and 25 g phosphorus pentachloride (caution), and after the initial reaction subsides, warm on the steam bath 10 minutes. Distill under reduced pressure to remove the POC1 and gradually add the residue to ice cold concentrated NH4OH. Filter, wash precipitate with water and air dry (can recrystallize from benzene with a little ethanol added) to get about 18 g (85%) of the substituted phenyl-acetamide (111). (Ill)... 

After exposure to atmospheres containing 300 and 600 ppm [1.30 and 2.60 g/m ] ethylbenzene for 6 h, Wistar rats excreted 83% and 59% of the estimated dose as ethylbenzene metabolites in the urine in 48 h, respectively. The principal metabolites were 1-phenylethanol, -hydroxyacetophenone and phenylacetic, mandelic, phenylglyoxylic and benzoic acids, accompanied by smaller amounts of 1-phenyl-1,2-ethanediol, phenylglyoxal, acetophenone and/ ara-hydroxyacetophenone (Engstrdm, 1984b). 

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... 

In the present paper we have studied four acid catalyzed reaotions involving carbonyl compounds alkylation of benzene with formaldehyde, esterification of phenylacetic acid, Friedel-Crafts acylation by phenylpropanoyl chloride, and the cross aldolic condensation of acetophenone with benzaldehyde in the presence of three Hp zeolites with different framework Si-to-Al... 

Equivalent protons. All hydrogens which are in identical environments have the same chemical shift and therefore absorb at the same frequency they are said to be chemically equivalent. This can arise in two ways. Firstly, the protons are equivalent if they are bonded to the same carbon atom which is also free to rotate. For example, the three protons in a methyl group are equivalent and appear as a singlet (see the spectra of toluene, anisole or acetophenone above), and the two protons of a methylene group, provided that it can rotate freely, are identical and appear as a singlet (see the spectrum of phenylacetic acid above) frequently this is not the case with methylene groups in cyclic systems where rotation is restricted. 

Atropine can be synthesized from tropi-none and tropic acid as starting materials. Tropinone can be prepared by Robinson s synthesis (68) and reduced under proper conditions to tropine. ( )-Tropic acid can be prepared from ethyl phenylacetate (69, 70) or acetophenone (71). The 0-acetyl derivative of tropyl chloride reacts with tropine to yield O-acetyl of atropine hydrochloride, from which the acetyl group hydrolyzes spontaneously in aqueous solution (72). 

Moreover, according to chemical structure, polyphenols can be divided in classes as simple phenols, benzoquinones, phenolic acids, acetophenones, phenylacetic acids, hrodroxycinnamic acids, phenylpropenes, coumarins, isocoumarins, chromones, naphthoquinones, xanthones, stilbenes, anthraquinones, lignans, neolignans, lignins, and flavonoids. The latter allow to consider 13 subclasses with more than 5,000 compounds (Fig. 74.2). 

Phenylacetamide from Acetophenone (Use of Sulfur, Aqueous Ammonia, and Pyridine)A mixture of 25 g. of acetophenone, 50 cc. of concentrated (15 M) aqueous ammonia, 37.5 g. of sulfur, and 30 cc. of pyridine is heated in a sealed glass tube at 150 for one hour and at 163° for tl ree and one-half hours (heating at 1 for four hours is equally effective). The tube is cooled and opened, the contents removed, and the mixture evaporated to dryness on a water bath. The residue is extracted with approximately 500 cc. of boiling water in several portions. From the filtrate, upon cooling, 20.0 g. of phenylacetamide, m.p. 156-158 (cor.), separates. Concentration of the filtrate affords 2.7 g. of additional amide. The oily residue from evaporation of the filtrate is washed with ether, whereupon 0.32 g. of amide separates, and from the ether layer 1.2 g. of phenylacetic acid is isolated. The acid melts at 76.3-77.3 (cor.) after recrystallization. The total yield of amide is... 

The roasted root contains a steam-distillable fraction (aroma), which is composed of pyra-zines, benzothiazoles, aldehydes, aromatic hydrocarbons, furans, phenols, organic acids, and others, totaling 3 3 identifiedcompounds, among which acetophenone is a characteristic component of roasted chicory not previously reported as a component of aroma of any heated food products such as coffee. Other constituents of the roasted root include 2-acetylpyrrole, furfural, phenylacetaldehyde, phenylacetic acid, and vanillin. Small amounts oftwo indole alkaloids ((3-carbolines), barman and norharman, have also been isolated from the roasted root. ... 

Dhavale, D. D., Mali, V. R, Sudrik, S. G., and Sonawane, H. R., Media controlled photo-Favorskii type rearrangement of a-chloro acetophenones synthesis of phenylacetic acids. Tetrahedron, 53,... 

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