Carboxylic acid reagents with carbon

Section 19 11 Carboxylic acids can be prepared by the reaction of Gngnard reagents with carbon dioxide... 

The methyl ester has also been obtained by esterification of cyclopentanecarboxylic acid.8 The acid, in turn, has been prepared by the Favorskii rearrangement,6 7 9-11 by the reaction of cyclopentyl Grignard reagent with carbon dioxide,12 by the carbonylation of cyclopentyl alcohol with nickel carbonyl13 or with formic acid in the presence of sulfuric acid,14 and by the hydrogenation of cyclopentene-1-carboxylic acid prepared from ethyl cyclopentanone-2-carboxylate 15 or from cyclopentanone cyanohydrin.16... 

Step 2b Reaction of a Grignard reagent with carbon dioxide affords the carboxylic acid. 

The reactions of Grignard reagents with aldehydes and ketones give alcohols, reaction with acid chlorides and esters give tertiary alcohols, reaction with carbon dioxide to give carboxylic acids, reaction with nitriles give ketones, and reaction with epoxides give alcohols. 

Aromatic carboxylic acids are prepared by reaction of a Grignard reagent with carbon dioxide, as either the solid or gas (Scheme 10.9). 

Aromatic carboxylic acids can be prepared by oxidation of the corresponding benzyl alcohols and benzaldehydes. An aromatic methyl group is also sufficiently activated by the aromatic ring for it to be oxidized to the acid under vigorous conditions, such as heating with chromium(VI) oxide. Other conventional methods include the hydrolysis of aromatic nitriles and the carboxylation of aromatic Grignard reagents with carbon dioxide. 

Preparation of carboxylic acids by the reaction of Grignard reagents with carbon dioxide is the most commonly used method. 

Carbon dioxide and bicarbonate have very different chemical reactivities. CO2 is quite reactive toward nucleophiles (J), reacting, for example, with hydroxide to form bicarbonate, with ammonia and primary and secondary amines to form carbamates, with enolates to form carboxylic acids, and with a variety of organo-metallic compounds (e.g., Grignard reagents and organolithium reagents) to form carboxylic acid salts (i). Bicarbonate is much less reactive. 

Nucleophilic Attack at Halogen. Further studies have been reported of the reactions of diols with the triphenylphosphine-carbon tetrachloride reagent. It has now been applied to 1,2-diols (in the presence of potassium carbonate) to form epoxides and to the trans-6 o (84), the nature of the product depending on the relative amounts of phosphine and diol present. The major product of reactions involving equimolar quantities of phosphine and diol is (85). The cyclodehydration product (86) is formed in only poor yield. In the presence of carboxylic acids, the triphenylphosphine-carbon tetrachloride system causes ring-opening of epoxides with the formation of c -enol esters, the reaction presumably proceeding via nucleophilic attack by the oxirane at an acyloxyphos-phonium intermediate. ... 

Reaction of a Grignard reagent with carbon dioxide, followed by treatment with aqueous HCI, gives a carboxylic acid. Propose a structural formula for the bracketed intermediate formed by the reaction of phenylmagnesium bromide with CO2, and propose a mechanism for the formation of this intermediate ... 

The Grignard reaction is used synthetically to prepare secondary alcohols from aldehydes and tertiary alcohols from ketones. The Grignard reagent will react with esters twice to give tertiary alcohols. Synthetically, it also can be allowed to react with carbon dioxide to give carboxylic acids and with oxygen to give hydroperoxides ... 

Reacting of a Grignard reagent with carbon dioxide produces a carboxylic acid product upon workup. This synthesis converts an alkyl (or aryl) halide to a carboxylic acid while also extending the carbon chain by one carlion. 

Carbojqrlic acids can be prepared by oxidation of primary alcohols and aldehydes. Problems 17.18-17.24, Treating a Grignard reagent with carbon dioxide (CO2) gives the magnesium 17.42,17.48 salt of a carboxylic acid, which, upon protonation with aqueous acid, gives a carboxylic acid. 

We already know a number of routes to carboxylic acids, and this section will add an important new one, the reaction of organometallic reagents with carbon dioxide. 

FIGURE 17.18 A general route to carboxylic acids uses the carboxylation of Grignard reagents with carbon dioxide. 

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