Carboxylation Grignard reagents

SYNTHESIS OF CARBOXYLIC ACIDS BY THE CARBOXYLATION OF GRIGNARD REAGENTS... 

We ve seen how Grignard reagents add to the carbonyl group of aldehydes ketones and esters Grignard reagents react m much the same way with carbon dioxide to yield mag nesium salts of carboxylic acids Acidification converts these magnesium salts to the desired carboxylic acids... 

Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents... 

Overall the carboxylation of Grignard reagents transforms an alkyl or aryl halide to a carboxylic acid in which the carbon skeleton has been extended by one carbon atom... 

Among the methods for preparing carboxylic acids carboxylation of a Grignard reagent and preparation and hydrolysis of a nitrile convert RBr to RCO2H The malonic ester synthesis converts RBr to RCH2CO2H... 

In some instances a carbon-carbon bond can be formed with C-nucleophiles. For example, 3-carboxamido-6-methylpyridazine is produced from 3-iodo-6-methylpyridazine by treatment with potassium cyanide in aqueous ethanol and l,3-dimethyl-6-oxo-l,6-dihydro-pyridazine-4-carboxylic acid from 4-chloro-l,3-dimethylpyridazin-6-(lH)-one by reaction with a mixture of cuprous chloride and potassium cyanide. Chloro-substituted pyridazines react with Grignard reagents. For example, 3,4,6-trichloropyridazine reacts with f-butyl-magnesium chloride to give 4-t-butyl-3,5,6-trichloro-l,4-dihydropyridazine (120) and 4,5-di-t-butyl-3,6-dichloro-l,4-dihydropyridazine (121) and both are converted into 4-t-butyl-3,6-dichloropyridazine (122 Scheme 38). 

Grignard reagents can be successfully prepared from 4-iodoisoxazoles and these react with CO2 and ketones to give carboxylic acids and methanols, respectively. 3-Bromo- or... 

Isoxazolyl Grignard reagents react normally in that a 4-carboxylic acid or 4-methanol can be obtained by reaction with CO2 or ketones (63AHC(2)365). Lithiation of 3,5-disub-... 

Grignard reagent from, acylation, 4, 237 nitration, 4, 211 reactivity, 4, 71-72 synthesis, 4, 149, 237, 341, 360 Pyrrole-3-carboxylic acids acidity, 4, 71 decarboxylation, 4, 286 esterification, 4, 287 esters... 

The other three methods have not been studied extensively. The dimethyl-cadmium route has been used on a 17a-methyl-17 -carboxylic acid. ° The reaction of the acid amide with a Grignard reagent is described only in a Spanish patent,with a high yield claimed, and the methyllithium reaction has apparently been tried only on D-norsteroids. ... 

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

Carboxylation (Section 19.11) In the preparation of a carboxylic acid, the reaction of a carbanion with carbon dioxide. Typically, the carbanion source is a Grignard reagent. 

Carboxylic acids don t give addition products with Grignard reagents because the acidic carboxyl hydrogen reacts with the basic Grignard reagent to... 

There are, of course, no Grignard reagents inside living cells, but there are other types of stabilized carbanions that are often carboxylated. One of the... 

Methods of synthesis for carboxylic acids include (1) oxidation of alkyl-benzenes, (2) oxidative cleavage of alkenes, (3) oxidation of primary alcohols or aldehydes, (4) hydrolysis of nitriles, and (5) reaction of Grignard reagents with CO2 (carboxylation). General reactions of carboxylic acids include (1) loss of the acidic proton, (2) nucleophilic acyl substitution at the carbonyl group, (3) substitution on the a carbon, and (4) reduction. 

Acid halides are among the most reactive of carboxylic acid derivatives and can be converted into many other kinds of compounds by nucleophilic acyl substitution mechanisms. The halogen can be replaced by -OH to yield an acid, by —OCOR to yield an anhydride, by -OR to yield an ester, or by -NH2 to yield an amide. In addition, the reduction of an acid halide yields a primary alcohol, and reaction with a Grignard reagent yields a tertiary alcohol. Although the reactions we ll be discussing in this section are illustrated only for acid chlorides, similar processes take place with other acid halides. 

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