Aryl acetates

Alkynes with EWGs are poor substrates for the coupling with halides. Therefore, instead of the inactive propynoate, triethyl orthopropynoate (350) is used for the coupling with aryl halides to prepare the arylpropynoate 351. The coupling product 353 of 3,3-dicthoxy-l-propyne (352) with an aryl halide is the precursor of an alkynal[260]. The coupling of ethoxy) tributylstan-nyl)acetylene (354) with aryl halides is a good synthetic method for the aryl-acetate 355[261]. 

Detailed mechanistic studies have been carried out on aminolysis of substituted aryl acetates and aryl carbonates. Aryl esters are considerably more reactive than alkyl esters because the phenoxide ions are better leaving groups than alkoxide ions. The tetrahedral intermediate formed in aminolysis can exist in several forms which differ in extent and site of protonation ... 

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. 

It is by now apparent that the nature of the aryl group in the aryl acetic and aryl propionic acid antiinflammatory agents can be varied quite widely without loss of activity. The corresponding derivatives of homologous xanthones and thioxanthones thus both show activity as nonsteroid antiinflammatory agents. 

For example, all three isomeric aryl acetates (1) undergo bromo- and iododesilylation, providing a route (6) to radio-halogen-labelled phenols the free phenols and methyl ethers corresponding to (1) proved too reactive, giving products of both substitution and desilylation. 

Phenolic compounds are weaker nucleophiles and better leaving groups than aliphatic alcohols. They do not yield polyesters when reacted with carboxylic acids or alkyl carboxy lates. The synthesis of polyesters from diphenols is, therefore, generally carried out through the high-temperature carboxylic acid-aryl acetate or phenyl ester-phenol interchange reactions with efficient removal of reaction by-product (Schemes 2.10 and 2.11, respectively). 

Carboxy-hydroxy reactions, 63 Carboxyl endgroup chemical titration, 94 Carboxylic acid-aryl acetate interchange reactions, 62, 63... 

From aryl acetates ortho para predominates (60 40)... 

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

R = alkyl, alkenyl, alkynyl, aryl, acetate, ester, benzyl or silyl ether groups Scheme 6.15 Cleavage of methoxyphenyl methyl (MPM) ethers using clayan. 

Fig. 4 A Bronsted plot of log pKz phenol in methanol vs. log fcaa fn( OCH3-) for methanolysis of aryl acetates promoted by 9 Zn2 + ( OCH3), T = 25°C, data in Table 7. Dashed line corresponds to NLLSQ fit of data to Equation (15) encompassing all esters with Pi = -0.023 0.03 and f 2 = -0.690 0.005 with a breakpoint of pJTa H = 14.8. Reproduced from ref. 16f with permission.

The reference intermolecular reaction is the nucleophilic attack of acetate on phenyl acetate, calculated by Page (1973) from the data of Gold et al. (1971) by extrapolation (from measurements on aryl acetates which show measurable nucleophilic catalysis). But see notes g and h... 

Bruice and Benkovic, 1963. The reference reaction is the attack of trimethylamine on the corresponding aryl acetate under the same conditions... 

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]. 

Selective monoalkylation of methyl aryl-acetates by alkylhalides is difficult with conventional bases. It may be achieved by application of the three-step procedure outlined above adding (33) to the methyl arylacetates at a low temperature... 

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

Aryl-acetic or -propionic acids as well as benzylketones are versatile intermediates for the synthesis of pharmaceuticals, agrochemicals, or fragrances. Many methods have already been explored, notably using electrochemistry and transition metal compounds. 

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... 

Table14 PFR of Several Aryl Acetates in the Presence and Absence of Potassium Carbonate...

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