ChemTalk

Decarboxylation

Core Concepts

This article serves as a guide to basic decarboxylation reactions. After reading this article, you will be able to understand and describe the reaction mechanism, its real-world applications, and its significance in organic chemistry.

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What is Decarboxylation?

Decarboxylation is a reaction in which a carboxyl group (COOH) is removed from a molecule and carbon dioxide (CO2) is released as a byproduct. There are multiple types of this reaction depending on how it is conducted. For example, thermal decarboxylation is one of the most common types and requires high temperatures. In this case, heating in the presence of a catalyst such as a metal or base results in a change in chemical structure.

Thermal decarboxylation primarily occurs in beta-keto acids such as malonic acid and its derivatives. Beta-keto acids are a type of carboxylic acid that have a carbonyl group (C=O) two carbons over from the carboxyl group. They spontaneously lose carbon dioxide when heated which produces a ketone. However, the majority of carboxylic acids do not spontaneously release carbon dioxide when heated and therefore do not undergo decarboxylation. For example, long-chain carboxylic acids such as butanoic acid simply boil when heated without loss of carbon dioxide. Additionally, it is worth noting that the reaction also occurs spontaneously in carbonic and carbamic acids.

An example of decarboxylation with malonic acid.

Reaction Mechanism

How the Reaction Works

Decarboxylation in organic chemistry is an example of a 1,2 elimination reaction. The mechanism of reaction is a concerted one with a cyclic transition state. It begins with the breaking of a carbon-to-carbon single bond (C-C). At the same time, carbon-to-oxygen double bonds (C=O) and a hydroxyl group (OH) are formed. An enol ends up being formed as an intermediate and it undergoes keto-enol tautomerism to produce a ketone.

decarboxylation mechanism
In this image, the first arrow (pointing to the right) shows that malonic acid is decarboxylated to form enol and carbon dioxide. The second arrow (pointing down) shows that the enol undergoes keto-enol tautomerism to form a ketone.

Electron Flow

A pair of electrons will move from the C-C bond toward the carboxyl group when it is broken. This pair of electrons will then move away from the carboxyl group and toward the carbon adjacent to the carbonyl group. The flow of electrons forms the C=O bonds which make up carbon dioxide and causes the leaving group to break off. The leaving group is specifically an enolate, a type of carbanion, and is what was initially attached to the carboxyl group.

decarboxylation electron flow
This image shows the electron flow in malonic acid when decarboxylated and the electron flow with the enolate intermediate to produce a ketone (acetone) with carbon dioxide.

Real-world Applications of Decarboxylation

  1. Pharmaceuticals: Decarboxylation has a critical role in the pharmaceutical industry as it is a widely used process in drug synthesis. Many medicinal drugs are synthesized in their inactive states and then become activated through decarboxylation within the body. Understanding the mechanism for this reaction is essential for drug synthesis. It ensures that medicinal compounds reach their intended target(s) in the body in their active states.
  2. Carbon sequestration: This reaction also has applications in carbon capture and storage in the context of climate change. Researchers are currently researching methods to capture and store carbon dioxide from industrial processes. The aim is to reduce greenhouse gas emissions to combat global warming.
  3. Culinary applications: Decarboxylation has seen use in culinary arts, especially with the making of edibles. Decarboxylating the plant material of cannabis activates the cannabinoids before infusing them into cooking ingredients. This ensures that the desired psychoactive or therapeutic effects of the cannabis will be present. In addition to this, decarboxylation is also present in the enhancement of flavors. For example, the reaction takes place when roasting coffee beans, contributing to the rich and aromatic flavors associated with coffee.
  4. Biofuel production: The reaction has applications in transforming organic matter into usable fuel. For example, removing the carboxyl group from fatty acids allows for the production of biofuels.
  5. Metabolism: Decarboxylation routinely occurs inside living organisms during cellular respiration. In particular, following glycolysis, pyruvate performs “oxidative decarboxylation” and later on, oxalosuccinate, a citric acid cycle intermediate, performs decarboxylation as well. Ultimately, this process of metabolic decarboxylation is why we exhale carbon dioxide!

Further Reading