Acetic acid derivation

Reactions. Heating an aqueous solution of malonic acid above 70°C results in its decomposition to acetic acid and carbon dioxide. Malonic acid is a useful tool for synthesizing a-unsaturated carboxyUc acids because of its abiUty to undergo decarboxylation and condensation with aldehydes or ketones at the methylene group. Cinnamic acids are formed from the reaction of malonic acid and benzaldehyde derivatives (1). If aUphatic aldehydes are used acryhc acids result (2). Similarly this facile decarboxylation combined with the condensation with an activated double bond yields a-substituted acetic acid derivatives. For example, 4-thiazohdine acetic acids (2) are readily prepared from 2,5-dihydro-l,3-thiazoles (3). A further feature of malonic acid is that it does not form an anhydride when heated with phosphorous pentoxide [1314-56-3] but rather carbon suboxide [504-64-3] [0=C=C=0], a toxic gas that reacts with water to reform malonic acid. 

A wide variety of /3-lactams are available by these routes because of the range of substituents possible in either the ketene or its equivalent substituted acetic acid derivative. Considerable diversity in imine structure is also possible. In addition to simple Schiff bases, imino esters and thioethers, amidines, cyclic imines and conjugated imines such as cinnamy-lidineaniline have found wide application in the synthesis of functionalized /3-lactams. A-Acylhydrazones can be used, but phenylhydrazones and O-alkyloximes do not give /3-lactams. These /3-lactam forming reactions give both cis and /raMS-azetidin-2-ones some control over stereochemistry can, however, be exercised by choice of reactants and conditions. 

The reactions of ketenes or ketene equivalents with imines, discussed above, all involve the imine acting as nucleophile. Azetidin-2-ones can also be produced by nucleophilic attack of enolate anions derived from the acetic acid derivative on the electrophilic carbon of the imine followed by cyclization. The reaction of Reformatsky reagents, for example... 

Coupling reactions of indole-3-acetic acid derivatives have also p ovided convenient routes to indolo[2,3-a]carbazoles (Scheme 5). An iodine-p-omoted coupling... 

Reaction of 2-pyrrolylbenzoic acid derivative 122 with PCI5 and subsequent reaction with diazomethane gave the diazoacetophenone 123 that upon treatment with silver oxide, sodium carbonate and sodium thiosulfate afforded acetic acid derivative 124, cyclization with acetic anhydride gave 125 (91JHC77) (Scheme 24). 

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. 

Note 2. To maintain integrity of carbohydrate names, it is sometimes helpful to overstep the strict order of principal group preference specified in general organic nomenclature [13,14]. For example, a carboxymethyl-substituted sugar can be named as such, rather than as an acetic acid derivative (see 2-Carb-31.2). 

Organoboranes can also be used to construct carbon-carbon bonds by several other types of reactions that involve migration of a boron substituent to carbon. One such reaction involves a-halo carbonyl compounds.20 For example, ethyl bromoac-etate reacts with trialkylboranes in the presence of base to give alkylated acetic acid derivatives in excellent yield. The reaction is most efficiently carried out with a 9-BBN derivative. These reactions can also be effected with (3-alkenyl derivatives of 9-BBN to give (3,y-unsaturated esters.21... 

Domino reactions are not a new invention - indeed, Nature has been using this approach for billions of years However, in almost of Nature s processes different enzymes are used to catalyze the different steps, one of the most prominent examples being the synthesis of fatty acids using a multi-enzyme complex starting from acetic acid derivatives. 

The addition of a carbonylation step extended a pyrrole synthesis to pyrrole-2-acetic acid derivatives <06ASC2212>. Treatment of enyne amine 1 with palladium diiodide in the presence of CO and methanol produced pyrrole-2-acetic ester 2 via a 5-exo-dig cyclization, oxidative carbonylation, and isomerization. 

There are very few precedents for the reaction of cyclic a-halo ethers with carbanions. Zelinski and coworkers114 and Schudel and Rice115 reported the preparation of diethyl DL-tetrahydropyran-2-ylmalonate (137) by treatment of 2-bromo- or 2-chloro-tetrahydropyran (136) with diethyl sodiomalonate. The product was subsequently converted into the malonic and acetic acid derivatives, 138 and 139, respectively. The same sequence has also been reported by other workers.116... 

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... 

Hirst, D.G. Wood, P.J. Chlorophenoxy acetic acid derivatives as hemoglobin modifiers and tumor radiosensitizers. 

Q89 Indometacin is an indole acetic acid derivative that has a lov/er frequency of gastrointestinal side-effects compared v/ith naproxen. Indometacin may cause headache and dizziness as side-effects. 

Indometacin is an indole acetic acid derivative, while naproxen is a propionic acid derivative. Both are non-steroidal anti-inflammatory drugs (NSAIDs). Indometacin is associated with a higher incidence of side-effects, particularly gastrointestinal as well as headache and dizziness. 

Heating ethyl 5-fluoro-4-[cyano(ethoxycarbonyl)methyl]-2,3-dihydro-l-methyl-7-oxo-l//,7//-pyrido[3,2,l-i7]cinnoline-8-carboxylate (83, R = COOEt) in a mixture of cone. HCl and acetic acid gave the 8-carboxy-4-acetic acid derivative (92EUP470578). The acetic acid group was decarboxylated by heating in boiling ethanol in the presence of NEts to give the 4-methyl derivative. When the 4-[cyano(tert-butoxycarbonyl)methyl]-8-carboxylate 83 (R = COOrBu) was treated with trifluoroacetic acid in methylene chloride at room temperature, the 4-cyanomethyl-8-carboxylate 83 (R = H) was obtained. 

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