Name: beta-ketoacids and carbon dioxide loss
Uploaded: 2023-04-30T10:20:35.000Z
Duration: 1 min 2 s
Channel: JoVE

Carboxylic acids bearing a keto group at the &#946; position to the carboxyl group are called &#946;-keto acids. When heated, these acids can readily undergo decarboxylation to lose CO2 gas while simultaneously generating a ketone.
The decarboxylation mechanism begins with the intramolecular hydrogen bonding between the &#946;-keto oxygen atom and the hydrogen atom of the carboxyl group, which generates a reactive conformation. 
As the partially protonated keto-oxygen is highly electrophilic, it leads to an internal electron transfer, proceeding through a six-membered cyclic transition state. 
Consequently, a C&#8211;C bond cleavage results in the formation of an enol, along with the evolution of CO2 as gas.
Finally, the enol undergoes facile keto-enol tautomerism to yield more stable ketones.

loss of carboxy group as co2: decarboxylation of &beta;-ketoacids

Loss of Carboxy Group as CO2: Decarboxylation of &beta;-Ketoacids

Carboxylic acids, upon heating, undergo a decarboxylation reaction by releasing carbon dioxide gas. Monocarboxylic acids do not undergo decarboxylation easily. However, a silver salt of carboxylic acid reacts with bromine or iodine under high temperature to release carbon dioxide gas and forms halide with one less carbon. This reaction is called the Hunsdiecker reaction.
<img alt="Organic synthesis equation, decarboxylation of silver carboxylate to alkyl bromide with CO2 and AgBr." src="/files/ftp_upload/12352/12352_PT_Figure_1.svg" style="text-align: center; height: 55px;" data-altupdatedat="1761830439000" data-alt="Figure1" />
Unlike monocarboxylic acids, &#42933;-keto acids bearing a keto group at the &#946; position to the carboxyl group, readily undergo decarboxylation under an acid medium to form a ketone and releases carbon dioxide gas.
<img alt="Decarboxylation reaction, chemical formula, &#946;-keto acid, organic chemistry process diagram." src="/files/ftp_upload/12352/12352_PT_Figure_2.svg" style="text-align: center; height: 60px;" data-altupdatedat="1761830439000" data-alt="Figure2" />
Decarboxylation reaction is biologically relevant while oxidizing food materials in the tricarboxylic acid (TCA) cycle. In this cycle, oxalosuccinic acid is formed as an intermediate that bears three carboxyl groups and one carbonyl group. However, as the carbonyl group is at the &#42933;-position to only one carboxyl group, only one of the three carboxyl groups undergoes decarboxylation to produce &#945;-ketoglutaric acid by losing CO2.
<img alt="Decarboxylation diagram of oxalosuccinic to &#945;-ketoglutaric acid, chemical reaction process." src="/files/ftp_upload/12352/12352_PT_Figure_3.svg" style="text-align: center; height: 128px;" data-altupdatedat="1761830439000" data-alt="Figure3" />

Carboxylic acids, upon heating, undergo a decarboxylation reaction by releasing carbon dioxide gas. Monocarboxylic acids do not undergo decarboxylation ...

loss-of-carboxy-group-as-co2-decarboxylation-of-ketoacids

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Organic Chemistry

Unit 1

Carboxylic Acids

KEY TERMS AND CONCEPTS

beta-ketoacids and carbon dioxide loss

Beta-ketoacids can lose a carboxyl group as carbon dioxide gas when they are heated in an acid medium. This reaction is called decarboxylation. Monocarboxylic acids, which have only one carboxyl group, do not decarboxylate easily under the same conditions.

Carboxylic acids can also undergo decarboxylation in another way. A silver salt of a carboxylic acid can react with bromine or iodine at high temperature. This Hunsdiecker reaction releases carbon dioxide gas and forms a halide with one fewer carbon atom.

Beta-ketoacids are different from monocarboxylic acids because they contain a keto group at the beta position to the carboxyl group. This arrangement makes decarboxylation easier. The reaction produces a ketone and carbon dioxide gas.

Decarboxylation is also important in biology. It helps during the oxidation of food materials in the tricarboxylic acid, or TCA, cycle. In this cycle, oxalosuccinic acid is an intermediate with three carboxyl groups and one carbonyl group. Because the carbonyl group is at the beta position to only one carboxyl group, only that one carboxyl group is lost. The product is alpha-ketoglutaric acid, formed after release of CO2.

Beta-Ketoacids and Carbon Dioxide Loss

iupac nomenclature of carboxylic acids

Naming Carboxylic Acids with IUPAC Rules

Carboxylic acids are named by IUPAC rules that focus on the carboxyl group, –COOH. For acyclic saturated monocarboxylic acids, the longest hydrocarbon chain that includes the –COOH carbon is chosen as the parent chain. The final -e in the parent hydrocarbon name is replaced with -oic acid, and numbering starts at the –COOH carbon. Substituents are then named and placed as prefixes in alphabetical order. In the presence of a carboxyl group, other groups such as –CHO, –CO–, –OH, –OR, –NH2, and...

physical properties of carboxylic acids

Carboxylic Acid Boiling Point Trends

Carboxylic acids have distinct physical properties that change with size and structure. Lower molecular weight carboxylic acids often have a sharp, unpleasant odor. They also tend to have higher boiling and melting points than similar aldehydes, ketones, and alcohols. Strong intermolecular hydrogen bonding helps explain these trends. The polar carbonyl and hydroxyl bonds create dipole-dipole interactions, and carboxylic acid molecules can form stable dimers. A dimer is a pair of molecules held...

acidity of carboxylic acids

Why Carboxylic Acids Are More Acidic

Carboxylic acids are the strongest organic acids, but they are still much weaker than mineral acids such as HCl. In water, they ionize by losing the hydroxyl proton. This forms a carboxylate ion, which is stabilized by resonance. The strength of this ionization is shown by the acid dissociation constant, or Ka, and the pKa value. For simple carboxylic acids, Ka is around 10^-5, and pKa is usually 4 to 5. These values show that carboxylic acids are moderately acidic. Carboxylic acids are more...

substituent effects on acidity of carboxylic acids

substituent-effects-on-acidity-of-carboxylic-acids

How Substituents Change Carboxylic Acid Strength

Carboxylic acid strength depends on the substituents attached to the acid group. The key factor is the stability of the carboxylate anion, which is the conjugate base formed when the acid loses a proton. An electron-withdrawing substituent makes the carboxylate anion more stable. It pulls electron density away through the inductive effect, which lowers the electron density on the carboxylate ion and increases acidity. An electron-donating substituent does the opposite. It pushes electron...

ir and uv&ndash;vis spectroscopy of carboxylic acids

ir-and-uvvis-spectroscopy-of-carboxylic-acids

Carboxylic Acid Bands in IR and UV-Vis

Carboxylic acids show clear signals in both IR and UV-Vis spectroscopy. Their IR spectra help identify the C=O bond and the O-H bond, while UV-Vis spectra show a weak absorption from an n→π* transition. In IR spectroscopy, the C=O bond usually appears as a characteristic band between 1710 and 1760 cm⁻¹. The O-H bond gives a broad band between 2500 and 3300 cm⁻¹. The exact C=O stretching frequency changes with structure. Free carboxylic acids show a higher stretching frequency at 1760 cm⁻¹.

nmr and mass spectroscopy of carboxylic acids

nmr-and-mass-spectroscopy-of-carboxylic-acids

Carboxylic Acid Signals in NMR and MS

Carboxylic acid signals in NMR and mass spectrometry help identify this functional group. In proton NMR, the acidic –COOH proton is strongly deshielded and usually appears far downfield at about 9–12 ppm. Its exact position can change with concentration and solvent. The nearby carbons also give useful clues. The α protons of carboxylic acids usually appear at 2–2.5 ppm, while the β protons show up farther upfield. A simple test uses deuterium oxide, or D2O, which swaps with the acidic proton...

preparation of carboxylic acids: overview

Making Carboxylic Acids from Oxidation

Carboxylic acids can be made by oxidation of several organic compounds. A primary alcohol or an aldehyde can be converted into a carboxylic acid with a strong oxidizing agent. Aldehydes can also be oxidized with a mild oxidizing agent. Alkyl benzenes with at least one benzylic hydrogen can also form benzoic acid. In this reaction, KMnO4 or Na2Cr2O7 is used under vigorous conditions such as heat and a high oxidant concentration. The product is benzoic acid exclusively. Alkynes can undergo...

preparation of carboxylic acids: hydrolysis of nitriles

preparation-of-carboxylic-acids-hydrolysis-of-nitriles

Nitrile Hydrolysis in Carboxylic Acid Synthesis

Nitrile hydrolysis is a useful way to make carboxylic acids from nitriles. A nitrile has the formula R-CN, and it can be converted into a carboxylic acid, R-COOH, with aqueous acid. Under base-catalyzed conditions, the product is a carboxylate anion, R-COO−. This reaction is also part of a two-step route from haloalkanes to carboxylic acids. First, a haloalkane reacts with sodium cyanide in an SN2 reaction to form a nitrile. Then the nitrile is hydrolyzed to give a carboxylic acid with one...

preparation of carboxylic acids: carboxylation of grignard reagents

preparation-of-carboxylic-acids-carboxylation-of-grignard-reagents

Adding Carbon to Grignard Reagents

Carboxylic acids can be made by adding carbon dioxide to a Grignard reagent. This reaction is useful because it turns alkyl, vinyl, benzyl, and aryl halides into carboxylic acids with one extra carbon atom. The process happens in two steps. First, the Grignard reagent attacks carbon dioxide and forms the magnesium salt of the carboxylate ion. Then an aqueous acid is added to protonate that salt and produce the carboxylic acid. The acid is added only after the first step is complete. A proton...

reactions of carboxylic acids: introduction

reactions-of-carboxylic-acids-introduction

Carboxylic Acid Reactions and Derivatives

Carboxylic acids are organic compounds with an acidic –COOH group. Their acidity comes from resonance stabilization of the conjugate base, which spreads the negative charge over both oxygen atoms. The carbonyl group is also polar because oxygen is highly electronegative. That makes the carbonyl carbon reactive and open to nucleophilic attack. Because of this reactivity, carboxylic acids can undergo nucleophilic acyl substitution. In these reactions, the –COOH group can be converted into acid...

carboxylic acids to esters: acid-catalyzed (fischer) esterification overview

carboxylic-acids-to-esters-acid-catalyzed-fischer-esterification

Driving Fischer Esterification to Esters

Fischer esterification makes esters from carboxylic acids and alcohols in an acidic medium. The reaction also produces water. Emil Fischer developed this condensation reaction in 1895. Hydroxy-functionalized carboxylic acids can react within the same molecule by intramolecular Fischer esterification. This forms lactones, which are cyclic esters. Five-membered and six-membered lactones form spontaneously. The reaction speed depends strongly on steric factors, or how crowded the molecules are...

carboxylic acids to esters: acid-catalyzed (fischer) esterification mechanism

Fischer Esterification: Building Esters from Acids

Fischer esterification is an acid-catalyzed reaction that turns a carboxylic acid and an alcohol into an ester. This condensation reaction is a common way to make esters in organic chemistry. It also involves nucleophilic acyl substitution, which means one group is replaced on the acid carbonyl. The reaction proceeds through a tetrahedral intermediate. During this step, the molecule briefly has a tetrahedral shape before the reaction moves forward. Water is then eliminated as the leaving group.

carboxylic acids to methylesters: alkylation using diazomethane

carboxylic-acids-to-methylesters-alkylation-using-diazomethane

Making Methyl Esters with Diazomethane

Carboxylic acids can be converted into methyl esters using diazomethane in an ether solvent. This reaction gives the methyl ester of the same acid and often does so in excellent yield. It is a useful esterification method in organic chemistry. Diazomethane is a yellow gas with a boiling point of minus 23 degrees Celsius. It is commonly prepared by treating N-methyl-N-nitrosourea or N-methyl-N-nitrosotoluenesulphonamide with a base. During the reaction, the carboxylic acid first protonates...

carboxylic acids to acid chlorides

Making Acid Chlorides from Carboxylic Acids

Carboxylic acids can be converted into acid chlorides using SOCl2 or PCl5. Acid chlorides are the most reactive carboxylic acid derivatives. They are also important synthetic reagents. In some aromatic compounds, they are useful for Friedel-Crafts acylation. Phosphorus pentachloride is one alternative reagent for this conversion. The carboxylic acid first attacks the phosphorus center of PCl5. This step removes a chloride ion. The chloride ion then attacks the carbonyl center and forms the...

carboxylic acids to primary alcohols: hydride reduction

carboxylic-acids-to-primary-alcohols-hydride-reduction

Selective Reduction of Carboxylic Acids

Carboxylic acids can be reduced to primary alcohols with the right reagent. Strong reducing agents, such as lithium aluminum hydride, first react with the acid and then are followed by hydrolysis, which gives the primary alcohol product. Not every hydride reagent works on carboxylic acids. Weaker reducers like lithium tri-tert-butoxyaluminum hydride and diisobutylaluminum hydride do not reduce carboxylic acids to primary alcohols. Borane in tetrahydrofuran, or THF, is another way to make this...

Beta-ketoacids can lose a carboxyl group as carbon dioxide gas when they are heated in an acid medium. This reaction is called decarboxylation. Monocarboxylic acids, which have only one carboxyl group, do not decarboxylate easily under the same conditions. Carboxylic acids can also undergo decarboxylation in another way. A silver salt of a carboxylic acid can react with bromine or iodine at high temperature. This Hunsdiecker reaction releases carbon dioxide gas and forms a halide with one...

loss of carboxy group as co2: decarboxylation of malonic acid derivatives

loss-carboxy-group-as-co2-decarboxylation-malonic-acid

Malonic Acid Decarboxylation and CO2 Release

Malonic acid derivatives can lose a carboxyl group as carbon dioxide during decarboxylation. This reaction is a useful way to turn a β-dicarboxylic acid into a monocarboxylic acid. It follows a pattern similar to the thermal decarboxylation of β-keto acids, which form ketones. The mechanism begins with an internal shift of electrons. That shift helps form a cyclic six-membered transition state, a short-lived arrangement of atoms during the reaction. The process then breaks a carbon-carbon bond...

key terms and concepts

Learn how beta-ketoacids decarboxylate to release carbon dioxide, how the Hunsdiecker reaction works, and why this reaction matters in the TCA cycle.

Beta-Ketoacids and Carbon Dioxide Loss | JoVE K12

organic chemistry

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Beta-Ketoacids and Carbon Dioxide Loss

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