Carboxylic acids strong bases reaction with

A fused tricyclic ring system based on an indole provides yet another NSAID. Michael addition of the anion from diethyl methylmalonate to cyclohexanone followed by acid hydrolysis of the product gives cyclohexanone (21-3), which incorporates the characteristic profen 2-substituted carboxylic side chain. Sequential reaction with para-chlorophenylhydrazine and a strong acid gives the fused indole... 

Fig. 13.10. Formation of carboxylate enolates ("carboxylic acid dianions") by reaction of carboxylic acid salts with strong bases.

The direct conversion of a carboxylic acid to an amide with NH3 or an amine is very difficult, even though a more reactive acyl compound is being transformed into a less reactive one. The problem is that carboxylic acids are strong organic acids and NH3 and amines are bases, so they undergo an acid-base reaction to form an ammonium sait before any nucleophilic substitution occurs. 

The carboxyl group, characteristic of organic acids, is very reactive, because it can be neutralized with bases forming either metal carboxylates or strong ion pairs with cations, and - in many cases - yielding sparingly soluble salts. All these reactions... 

The hydrolysis of an ester by a strong base is called saponification (from Latin sapon, soap) because this reaction is used to make soaps from esters of long-chain carboxylic acids. Methyl acetate reacts with a strong base to give acetate ion and methanol. 

The treatment of 3-benzoyl-2-phenylisoxazolidine with strong base generated an aldehyde and a ketimine <74X1121). Under these conditions dimethyl 2-a-methoxyisoxazolidine-3,3-dicarboxylic acid (186) produced isoxazoline-2-carboxylic acid. Reaction of the monomethyl amide (187) gave the corresponding isoxazoline-2-carboxamide (Scheme 60). CD was used in the conformational studies <79X213). 

Aldehydes 1 that have no a-hydrogen give the Cannizzaro reaction upon treatment with a strong base, e.g. an alkali hydroxide.In this disproportionation reaction one molecule is reduced to the corresponding alcohol 2, while a second one is oxidized to the carboxylic acid 3. With aldehydes that do have a-hydrogens, the aldol reaction takes place preferentially. 

Alpha hydrogen atoms of carbonyl compounds are weakly acidic and can be removed by strong bases, such as lithium diisopropylamide (LDA), to yield nucleophilic enolate ions. The most important reaction of enolate ions is their Sn2 alkylation with alkyl halides. The malonic ester synthesis converts an alkyl halide into a carboxylic acid with the addition of two carbon atoms. Similarly, the acetoacetic ester synthesis converts an alkyl halide into a methyl ketone. In addition, many carbonyl compounds, including ketones, esters, and nitriles, can be directly alkylated by treatment with LDA and an alkyl halide. 

Treatment of a carboxylic acid with the strong base NaOH harms the sodium salt of the acid. With acetic acid, the acid-base reaction is... 

Carboxylic acids can be alkylated in the a position by conversion of their salts to dianions [which actually have the enolate structures RCH=C(0")2 ] by treatment with a strong base such as LDA. The use of Li as the counterion is important, because it increases the solubility of the dianionic salt. The reaction has been applied to primary alkyl, allylic, and benzylic halides, and to carboxylic acids of the form RCH2COOH and RR"CHCOOH. This method, which is an example of the alkylation of a dianion at its more nucleophilic position (see p. 458),... 

Carboxylic esters can be treated with ketones to give p-diketones in a reaction that is essentially the same as 10-118. The reaction is so similar that it is sometimes also called the Claisen condensation, though this usage is unfortunate. A fairly strong base, such as sodium amide or sodium hydride, is required. Yields can be increased by the catalytic addition of crown ethers. Esters of formic acid (R H) give P-keto aldehydes. Ethyl carbonate gives P-keto esters. 

The whole range of carboxylic acids and alcohols can be reacted to form esters. They are found in a large number of natural and synthetic scents and perfumes because of their pleasant odor. Many are used as solvents for paints and resins. Esters are converted back into the original acids and alcohols hy reaction with strong bases in water in a process called saponification (soap formation). 

Since both hydrolysis and acylation yield the release of carboxylic acid functionalities, the medium becomes acidic during the course of the reaction. This requires either the presence of a strongly buffered environment to maintain the pH or periodic monitoring and adjustment of the pH with base as the reaction progresses. 

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