MCAT Organic Chemistry

Keto Acids & Esters

MCAT Organic Chemistry > Keto Acids and Esters

Background

Esters are molecules.

Keto acids, also known as oxo acids are organic compounds that contain a carboxylic acid and a ketone functional group.

Keto Esters are organic compounds that contain an ester and a ketone functional group.

Esters that have a carbonyl group on the alpha carbon of the ester group are called α-keto esters.

Esters that have a carbonyl group on the beta carbon are called β-keto acids.

A ketone has two alkyl (or aryl) groups bonded to a carbonyl group.

Nomenclature

Ketones are named with the suffix –one.

When it is necessary to name the ketone as a substituent, the prefix oxo- is used.

Carboxylic acids that have a carbonyl group on the alpha carbon of the carboxylic acid chain are called α-keto acids. Carboxylic acids that have a ketone on the beta carbon are called β-keto acids.

Common NameIUPAC NameExampleStructure
α-keto acids2-oxo acidα-ketopropanoic acidMCAT Keto Acids and Esters - 2 Oxopropanoic Acid
β-keto acids3-oxo acidβ-ketobutanoic acidMCAT Keto Acids and Esters - 3 Oxobutanoic Acid
α-keto esters2-oxo esterethyl α-ketobutanoateMCAT Keto Acids and Esters - Ethyl-3-oxopropanoate
β-keto esters3-oxo ester ethylethyl β-ketobutanoateMCAT Keto Acids and Esters - Ethyl-3-oxobutanoate

Properties

This class of compounds readily decarboxylate when enough heat is applied. The temperature range at which β-keto acids decarboxylate can range from 100°C to 150°C. However, some β-keto acids can even undergo decarboxylation at room temperature!

Alpha Hydrogen Acidity

When a hydrogen is on a carbon adjacent to an electron withdrawing group such as a carbonyl group, it is more acidic than a typical hydrogen-carbon bond. In compounds containing carbonyl groups, an alpha hydrogen’s acidity increases further because of enolate resonance structure stabilization which occurs for de-protonated species.

MCAT Keto Acids and Esters - Acidic Keto Ester

In keto acids and keto esters, since the alpha carbon is flanked by two carbonyl groups, the de-protonated intermediate is further stabilized by enolate stabilization, increasing the acidity of the alpha hydrogen further.

An enolate is the anion that is produced when a carbonyl compound loses a proton from an alpha carbon. This anion is stabilized by delocalization of the negative charge. This anion forms because carbonyl groups are such strong electron withdrawing groups, that when the weakly held hydrogen is lost and a negative charge is gained on the alpha carbon, the negative charge is, overall, shared evenly between the alpha carbon, carbonyl carbon, and oxygen through sigma bonds.

The alpha hydrogen in a β-keto ester is the most acidic because it is adjacent to two carbonyl groups.

Keto–Enol Tautomerism

Tautomers are interconvertible keto and enol forms of a compound, and their interconversion is called tautomerism. From the enolate anion, either keto or enol forms may be produced. The keto form is produced when a hydrogen bonds with the alpha carbon of the enolate, producing a ketone group.

MCAT Keto Acids and Esters - Keto Enol Tautomerism

An enol group is formed when a hydrogen bonds with the oxygen of the enolate, forming a hydroxyl alcohol (-OH) group. Under the vast majority of circumstances, keto-enol tautomers are found in a state of equilibrium.

The keto form is preferred in compounds that contain only one carbonyl group, such as acetaldehyde as it is usually more stable. A keto group can also be known as a ketone group. In fact, the equilibrium favors the keto form so much, that almost no enol form exists in solution. Such is the case with many monocarbonyl compounds.

The enol form is favored in compounds that have two carbonyl groups separated by one carbon atom, also known as β-dicarbonyl compounds, such as the keto acids and esters studied earlier. In the case of pentane-2,4-dione, it exists in the enol form to the degree of 760. This is because the conjugated bonding resonance structure of enol forms in β-dicarbonyl compounds contributes much more stability to its hybrid structure than that of the structure that is made up of two carbonyl groups.

This concept also appears in aldehydes and ketones.

Keto Acid & Esters Reactions

Decarboxylation

β-keto Esters → β-keto acids → Enols → Ketos

Decarboxylation is a chemical reaction that removes a carboxyl group from a target compound and produces carbon dioxide. This results in the removal of a carbon atom from a carbon chain. The carbon removed in this reaction is the carboxylate group, -COOH. The enol in this reaction stabilizes the reaction intermediate.

These reactions are usually carried out by heating the compound to between 100°C and 150°C, so when you see a keto acid or keto ester and an indication that a reaction is heated, this is the reaction you are dealing with!

***Whenever a carbon is removed from a compound on the MCAT, it will be done using this reaction, and will be lost in the form of carbon dioxide.***

Acetoacetic Ester Synthesis

2Ethylacetate → Ethyl acetoacetate

Acetoacetic ester is synthesized by carrying out a process called Claisen Condensation of ethyl acetate, known as acetoacetic ester condensation. Then, with our newly formed acetoacetic ester (β-keto ester), we carry out an acetoacetic ester synthesis.

In an acetoacetic ester synthesis, the acidic alpha proton is pulled off and the resulting carboanion will attack the new R functional group. Next. the hydrolysis of the ester transforms it into a β-keto carboxylic acid which then undergoes decarboxylation. The decarboxylation occurs because the β-keto acid help stabalize the carboanion through enol formation.

The enol converts back to the keto form and finally the net result is the R group attaches to the alpha carbon of acetone. The end product of the acetoacetic ester synthesis is a ketone.

MCAT Organic Chemistry

Organic Chemistry Topics