Grignard reaction with carbon dioxide

Fig. Mechanism for the Grignard reaction with carbon dioxide.

Section 19.11 Carboxylic acids can be prepared by the reaction of Grignard reagents with carbon dioxide. 

The Grignard reagent from 2-thenyl chloride can be obtained by the use of the "cyclic reactor.However, rearrangement occurs in its reaction with carbon dioxide, ethyl chlorocarbonate, acetyl chloride, formaldehyde, and ethylene oxide to 3-substituted 2-methylthio-phenes, Only in the case of carbon dioxide has the normal product also been isolated. 

Carboxylic acids are obtained from Grignard reagents by reaction with carbon dioxide. Scheme 7.3 includes some specific examples of procedures described in Organic Syntheses. 

Bromobenzocyclobutene 2 is converted to 4-benzocyclobutenyl carboxylic acid 3 by either of two routes (Fig. 2). The first method of preparation proceeds from the corresponding Grignard reagent of 2 followed by reaction with carbon dioxide [38], The acid 3 is obtained in a yield of 60-70%. The second method for the formation of 3 again starts with 4-bromobenzocyclobutene, but in this case 2 is reacted with a palladium zero catalyst in the presence of carbon monoxide and methanol to provide 4-carbomethoxybenzocyclobutene, 4 in a yield of > 95% [39, 40]. Ester 4 is hydrolyzed under standard conditions to provide 3 in an overall yield of 90% for the two steps [36]. 

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... 

Lithiation of dibenzofuran with butyllithium and mercuration both occur at the 4-position. Thallation occurs at the 2-position, however (57IZV1391). The mercury and thallium derivatives serve as a source of the iodo compounds by reaction with iodine. Bromodibenzofurans undergo bromine/lithium exchange with butyllithium and the derived lithio compounds may be converted into phenols by reaction with molecular oxygen in the presence of a Grignard reagent, into amines by reaction with O-methylhydroxylamine, into sulfinic acids by reaction with sulfur dioxide, into carboxylic acids by reaction with carbon dioxide and into methyl derivatives by reaction with methyl sulfate (Scheme 100). This last reaction... 

For some purposes (e.g. in the Grignard reaction) solid carbon dioxide marketed as Cardice , Dry Ice or Drikold may be employed. Lumps of solid carbon dioxide should not be picked up with unprotected hands otherwise frostbite may result. If powdered material is required, the larger lumps should be wrapped in cloth and hammered. Solid carbon dioxide affords a convenient regulated supply of the gas when suitably sized lumps are allowed to evaporate in a Buchner flask attached to a sulphuric acid drying train. 

The Grignard reagent is highly reactive and is used to prepare many functional groups. An example is the preparation of a carboxylic acid by reaction with carbon dioxide and mineral acid. 

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. 

Reaction of Grignard reagents with carbon dioxide... 

Aromatic carboxylic acids are readily prepared from aryl halides by conversion to the Grignard reagent or aryllithium compound and subsequent reaction with carbon dioxide (see Chapter 10). 

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

A Reaction of Grignard Reagents with Carbon Dioxide... 

The triphenylmethyl carbanion, the trityl anion, can be generated by the reaction of triphenylmethane with the very powerful base, n-butyllithium. The reaction generates the blood-red lithium triphenylmethide and butane. The triphenylmethyl anion reacts much as a Grignard reagent does. In the present experiment it reacts with carbon dioxide to give triphenylacetic acid after acidification. Avoid an excess of n-butyllithium on reaction with carbon dioxide, it gives the vile-smelling pentanoic acid. 

In general, the acetylenic triple bond is highly reactive toward hydrogenation, hydroboration, and hydration in the presence of acid catalyst. Protection of a triple bond in disubstituted acetylenic compounds is possible by complex formation with octacarbonyl dicobalt [Co2(CO)g Eq. (64) 163]. The cobalt complex that forms at ordinary temperatures is stable to reduction reactions (diborane, diimides, Grignards) and to high-temperature catalytic reactions with carbon dioxide. Regeneration of the triple bond is accomplished with ferric nitrate [164], ammonium ceric nitrate [165] or trimethylamine oxide [166]. 

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 ... 

Organic acids can be prepared in many ways, four of which are described here (1) oxidation of primary alcohols or aldehydes, (2) oxidation of alkyl side chains on aromatic rings, (3) reaction of Grignard reagents with carbon dioxide, and (4) hydrolysis of alkyl cyanides (nitriles). 

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