Aryl acetic acid

I he potent antiinflammatory action exerted by many aryl acetic acid derivatives has led to the continued exploration of this class. It is apparent from a consideration of the structures of compounds that have become prominent that considerable structural latitude is possible without loss of activity. 

The Arndt-Eistert method is useful for making aryl-acetic acids from benzoic acids. How would you carryout this conversion ... 

Different nucleophiles such as methanol, allylsilanes, silyl enol ethers, trimethylsilyl-cyanide, and arenes can be used in this process [62]. When the sulfide itself contains an unsaturated or aromatic fragment and the process is carried out in the absence of a nucleophile, an intramolecular anodic sub-stitution/cyclization might occur [61-63]. Methyl esters of 2-benzothiazolyl-2-alkyl or aryl-acetic acid, oxidized in MeOH/Et4 NCIO4 or H2SO4 in the presence of CUCI2, form 2,2-dimethoxy products (Eq. 7) [64]. 

Homocoupling of aryl acetic acid derivatives has been achieved by deprotonation and oxidation by I2 as outlined... 

For therapeutical purposes, a likewise frequently used group of drug compounds are the nonsteroidal anti-inflammatory drugs (NSAID). Among the best known representatives of the aryl acetic acid derivatives is diclofenac as well as ibuprofen, an aryl propionic acid derivative. As both have acidic properties, they dissociate while being dissolved and may form salts with amphiphilic properties. Together with appropriate counterions these amphiphilic organic acids may form lyotropic mesophases with water even at room or body temperature, for example, diclofenac diethylamine... 

A few years ago, Blagonev and Ivanov described the bis-deprotonation of aryl acetic acids by Grignard reagents. These magnesinm dianions, known as Ivanov reagents, react with aldehydes and ketones. Reaction between dianions of phenylacetic acid and benzaldehyde yields the anti S-hydroxy acid as the major diastereomer anti/syn 69/22) (equation 113). This result is in agreement with the formation of a cyclic chair-like transition state according to the model of Zimmerman-Traxler . 

He made both starting materials from esters of the corresponding aryl acetic acids 53 and 56 by reduction and substitution (in the case of the phosphonium salt). This gave added flexibility as either component can be used as the phosphonium salt 55 or the aldehyde 54. He used the unusual reducing agent REDAL [NaAlH2(0CH2CH20Me)2] instead of DIB AL to make the aldehyde 54. 

Chiral aryl acetic acids constitute a privileged class of target structures due to their prevalence in bioactive natural products and pharmaceuticals and so, unsurprisingly, they constitute attractive targets for asymmetric synthesis [198]. The face-selective addition of a nucleophile to an aryl alkyl ketene provides a very direct entry for the preparation of such compounds. Although this can be achieved by the use of a chiral nucleophile or acid (cf. Scheme 8.1) [199], catalysis of the addition of an achiral nucleophile is clearly attractive from the standpoint of efficiency. 

In another nonelectrolytic process, aryl acetic acids are converted to vic-diaryl com-ponnds 2ArCR2COOH ArCRaCRaAr by treatment with sodinm persulfate Na2S20g and a catalytic amormt of AgN03-" Photolysis of carboxylic acids in the presence of Hg2p2 leads to the dimeric alkane via decarboxylation. Both of these reactions involve dimerization of free radicals. In still another process, electron-deficient aromatic acyl chlorides are dimerized to biaryls (2 ArCOCl Ar—Ar) by treatment with a disUane R3SiSiR3 and a palladium catalyst. ... 

Ivanov reagent. Reaction product of aryl acetic acids and excess Grignard reagent. The reagent may be used in condensations with carbonyl compounds and other Grignard-type reactions. 

Acetamidoeugenol is an intravenous anesthetic of ultra-short duration of action, it has been withdrawn because it provokes irritations and lesions of the vascular wall. Acetamidoeugenol is oxidized very rapidly in vivo into the corresponding aryl-acetic acid. This observation was the basis of the synthesis of another intravenous short-acting anesthetic such as propanilide. ... 

Tetramic acids are substructures of natural products that show antimicrobial activity. An access to these structures started from Wang resin-bound Fmoc-protected amino acids, which were deprotected and reductively alkylated. These intermediates 111 were transformed into amides, for example with malonic acid monoesters or aryl acetic acids (112 and 114, respectively). Cyclative cleavage was induced with 0.1 M NaOEt at 85 °C and gave substituted tetramic acids 113 and 115 in yields and purities of generally >95% (Scheme 30) [46]. 

Aryl acetic Acids - Of several aryl acetic acids described in the last report, no significant developments have been noted regarding ibufenac and namoxyrate. Detailed pharmacology and toxicity data on... 

Aryl acetic acid derivatives are notable for their failure to... 

Isoflavones (3-aryl-chromones) can also be prepared in this way boron trifluoride-catalysed Friedel-Crafts acylation of a reactive phenol with an aryl acetic acid is followed by reaction with dimethylfor-mamide and phosphorus pentachloride. ... 

The acylation of 6-APA with a,a-disubstituted aryl acetic acids yielded penicillins carrying a substituent on the a or benzylic carbon of the R side chain. Those of particular interest were penicillins carrying the polar -NH2 group (i.e., a-aminobenzyl penicillins) (Table 6-2, No. 13). The fact that this compound was acid stable and orally absorbed was not particularly novel (see penicillin V). Its antistaphylococcal activity was 25-60% less than that of penicillin G (the D-isomer was more active than the racemic d, l). However, its antibacterial spectrum was dramatically different. Ampicillin s spectrum, unlike previous penicillins, encompassed many important Gm- bacteria. Species of Hemophilus, Proteus, Salmonella, Shigella, and Escherichia succumbed to ampicillin. Even though resistant... 

A further application of this approach is the s)mthesis of 1,2-diaryl-l-ethanones 12 in good to excellent yields by reaction of aryl acetic acids 11 with arenes in the presence of 85% phosphoric acid without solvent at 50°C for 30-180 min (Scheme 2.7). The reaction tolerates a variety of substituents, and groups such as methoxy and thiomethoxy are found to be highly effective. 

Lambertwished to study the effect of an adjacent leaving group on the performance of another and so he wanted single diastereoisomers of di-tosylates (22) with a variety of aryl groups. These are esters of 1,2-diols (23), which can be made stereospecifically from alkenes (24). Wittig disconnection gives (25) and (26) both made from commercially available aryl acetic acids... 

There are three major classes of synthetic auxins the aryl acetic acids, which include indoleacetic acid (lAA) itself (Fig. 1 structure 2-1) and 1-naphthyl acetic acid (2-4), phenoxy acetic acids, represented by 2,4-dichlorophenoxy acetic acid (2,4-D) (2-7) and the benzoic acids, e.g. 2,3,6-trichloro benzoic acid (2-9). It remains the case however, that there is no stmcture-activity proposal which satisfactorily covers all molecules which are known to have auxin activity. As is well known, auxins have multiple effects, including promotion of cell elongation, cell division and gene expression. There may well be different receptors for each effect, and differences between receptors. An auxin binding protein (ABP), has now been characterised, and is possibly a receptor controlling cell elongation [3]. 

A sequence of bromination of a 3-indolyl acyl group followed by azide displacement and reduction, provides an effective route to 3-(a-aminoacyl)indoles <88JHC469>. Indoles react readily with oxalyl chloride at C-3 and the products have been used in combination with aryl acetic acid derivatives to generate indolyl-substituted maleic anhydrides and imides, as precursors for indolocarbazole antibiotics <90TL2353,93TL5623>. 

Several possibilities for a large-scale synthesis of mesitylacetic acid 12, a central building block in the synthesis of spiromesifen 8a, were examined (Scheme 28.4.2). Using the classical standard route, mesitylene 13 is transferred into mesityl acetonitrile 14 via chloromethylation and cyanide exchange, which is then saponified to the aryl acetic acid. Another route examined is the Friedel-Crafts alkylation of mesitylene with 1,3-dichloro-propene to the adduct 15, which is ozo-nolyzed to the corresponding aldehyde in the form of its dimethyl acetal and than further oxidized with hydrogen peroxide under acidic conditions to mesityl acetic... 

Besides the aldol reaction to form y0-hydroxyketone, 1,3-Dipolar Cycloaddition can also form similar molecules. In addition to the Mukaiyama Aldol Reaction, the following are also similar or closely related to the aldol reaction the Claisen-Schmidt Condensation (the aldol reaction between benzaldehyde and an aliphatic aldehyde or ketone in the presence of relatively strong bases to form an o, )0-unsaturated aldehyde or ketone), the Henry Reaction (base-catalyzed addition of nitroalkane to aldehydes or ketones), the Ivanov Reaction (the addition of enediolates or aryl acetic acid to electrophiles, especially carbonyl compounds), the Knoevenagel Reaction (the condensation of aldehydes or ketones with acidic methylene compounds in the presence of amine or ammonia), the Reformatsky Reaction (the condensation of aldehydes or ketones with organozinc derivatives of of-halo-esters), and the Robinson Annulation Reaction (the condensation of ketone cyclohexanone with methyl vinyl ketone or its equivalent to form bicyclic compounds). 

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