Krapcho decarboxylation is a chemical reaction used to manipulate certain organic

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

s. This reaction applies to

s with a beta

electron-withdrawing group An electron-withdrawing group (EWG) is a Functional group, group or atom that has the ability to draw electron density toward itself and away from other adjacent atoms. This electron density transfer is often achieved by resonance or inductive effe ...

(EWG). The reaction proceeds by nucleophilic dealkylation of the ester by the halide followed by decarboxylation, followed by hydrolysis of the resulting stabilized carbanion. :

Reaction conditions

The reaction is carried in dipolar aprotic solvents such as

dimethyl sulfoxide Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula . This colorless liquid is the sulfoxide most widely used commercially. It is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is ...

(DMSO) at high temperatures, often around 150 °C. A variety of salts assist in the reaction including

NaCl Sodium chloride , commonly known as edible salt, is an ionic compound with the chemical formula NaCl, representing a 1:1 ratio of sodium and chloride ions. It is transparent or translucent, brittle, hygroscopic, and occurs as the mineral hali ...

, LiCl, KCN, and NaCN. It is suggested that the salts were not necessary for reaction, but greatly accelerates the reaction when compared to the reaction with water alone. The ester must contain an EWG in the beta position . The reaction works best with a

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...

esters. which are more susceptible to S_N2 reactions.

Mechanisms

The mechanisms are still not fully uncovered. However, the following are suggested mechanisms for two different substituents: α,α-Disubstituted ester For an α,α-disubstituted ester, it is suggested that the anion in the salt attacks the R₃ in an S_N2 fashion, kicking off R₃ and leaving a negative charge on the oxygen. Then, decarboxylation occurs to produce a carbanion intermediate. The intermediate picks up a hydrogen from water to form the products. : Krapcho Decarboxylation Disubstituted Beta Carbon Mechanism

Krapcho Decarboxylation Disubstituted Beta Carbon Mechanism

The byproducts of the reaction (X-R₃ and CO₂) are often lost as gases, which helps drive the reaction;

entropy Entropy is a scientific concept, most commonly associated with states of disorder, randomness, or uncertainty. The term and the concept are used in diverse fields, from classical thermodynamics, where it was first recognized, to the micros ...

increases and

Le Chatelier's principle In chemistry, Le Chatelier's principle (pronounced or ) is a principle used to predict the effect of a change in conditions on chemical equilibrium. Other names include Chatelier's principle, Braun–Le Chatelier principle, Le Chatelier–Braun p ...

takes place. α-Monosubstituted ester For an α-monosubstituted ester, it is speculated that the anion in the salt attacks the

carbonyl group In organic chemistry, a carbonyl group is a functional group with the formula , composed of a carbon atom double-bonded to an oxygen atom, and it is divalent at the C atom. It is common to several classes of organic compounds (such as aldehydes ...

to form a negative charge on the oxygen, which then cleaves off the cyanoester. With the addition of water, the cyanoester is then

hydrolyzed Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysi ...

to form CO₂ and alcohol, and the carbanion intermediate is protonated. : The byproduct of this reaction (CO₂) is also lost as gas, which helps drive the reaction;

increases and

takes place.

Advantages

The Krapcho decarboxylation is a comparatively simpler method to manipulate malonic esters because it cleaves only one ester group, without affecting the other ester group. The conventional method involves

saponification Saponification is a process of cleaving esters into carboxylate salts and Alcohol (chemistry), alcohols by the action of aqueous alkali. Typically aqueous sodium hydroxide solutions are used. It is an important type of alkaline hydrolysis. When the ...

to form carboxylic acids, followed by

decarboxylation Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is ...

to cleave the carboxylic acids, and an

esterification In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

step to regenerate the esters. Additionally, Krapcho decarboxylation avoids harsh alkaline or acidic conditions.

References

{{Reflist Elimination reactions Substitution reactions Name reactions