Carboxylic Acids | Organic Chemistry 2
Nomenclature of Carboxylic Acids
Name: the -ane ending of the corresponding alkane is replaced by -oic acid.
- The parent is the longest chain containing the carbon atom of the carboxylic acid. The carbon of the carboxylic acid is always assigned the number 1 when numbering the parent ⇒ the 1 is not mentioned in the final name.
- The aromatic counterparts are called benzoic acids.
- When a carboxylic acid is connected to a ring, the compound is named as an alkane carboxylic acid.
Many simple carboxylic acids have common names accepted by IUPAC and should be memorized:
Properties of Carboxylic Acids
- Polarity: The carbonyl bond (C=O) is short, strong and highly polar due to the electronegativity difference between carbon and oxygen. The C-O and OH bonds are also polar ⇒ significant dipole moment.
- Carboxylic acids can form 2 hydrogen bonding interactions ⇒ carboxylic acids often exist as dimers.
- Solubility: Carboxylic acids are soluble in organic solvents. Molecules with less than 6 carbons are soluble in water, favored by the formation of hydrogen bonds.
- Boiling and melting points: Higher than other compounds of comparable molecular weight due to the presence of strong dipole-dipole interactions.
Geometry and orbitals:
The carbon of the C=O bond of carboxylic acids is sp2 hybridized ⇒ trigonal planar geometry.
The C-O single bond of a carboxylic acid is shorter than the C-O single bond of an alcohol due to the sp2 hybridization (higher percentage of s-character).
- 1H NMR: δ ~ 10-13 ppm
Highly deshielded O-H proton (farther downfield absorption than any other absorption of common organic compounds).
- 13C NMR: δ ~ 160-185 ppm
Highly deshielded carbonyl carbon.
- IR absorptions: ~ 1760 cm-1 (intense band, C=O stretching), 2500-3300 cm-1 (broad band, O-H stretching).
Reactivity of carboxylic acids:
- Deprotonation: Carboxylic acids exhibit mildly acidic protons ⇒ treatment with a strong base (e.g., NaOH) yields a carboxylate salt.
- Nucleophilic addition: The carbonyl carbon is electrophilic and susceptible to nucleophilic addition reactions.
Acidity of Carboxylic Acids
Formation of carboxylate salts:
The pKa of most carboxylic acids is between 4 and 5 ⇒ a carboxylic acid can be deprotonated by a base that has a conjugate acid with a higher pKa (e.g., NaOH, NaHCO3).
The acidity of carboxylic acids is due to the stability of the conjugate base, which is resonance stabilized: the negative charge is delocalized over two electronegative oxygen atoms.
Substituent Effects on Carboxylic Acids Acidity
General effect of substituents:
- Electron withdrawing groups stabilize a carboxylate anion, making a carboxylic acid more acidic.
- Electron donating groups destabilize a carboxylate anion, making a carboxylic acid less acidic.
- A carboxylic acid is more acidic than an alcohol due to the resonance stabilization of its conjugate base.
- A carboxylic acid is more acidic than a phenol because its conjugate base is more effectively stabilized by resonance: the carboxylate anion has 2 electronegative oxygen atoms on which to delocalize the negative charge, whereas the phenoxide has only one.
The number, electronegativity, and position of the substituents affect the acidity:
- The larger the number of electronegative substituents, the stronger the acid.
- The more electronegative the substituent, the stronger the acid.
- The closer the electron withdrawing group to the carboxylic acid, the stronger the acid.
Substituted benzoic acids:
- Electron withdrawing groups make a substituted benzoic acid more acidic than benzoic acid.
- Electron donating groups make a substituted benzoic acid less acidic than benzoic acid.
Preparation of Carboxylic Acids
Oxidation of primary alcohols:
Primary alcohols are converted to carboxylic acids with a variety of strong oxidizing agents (e.g., Na2Cr2O7, K2Cr2O7, CrO3) in the presence of H2O and H2SO4.
Oxidation of alkylbenzenes:
An alkyl group on an aromatic ring with at least one hydrogen atom at the benzylic position will be completely oxidized to give benzoic acid. Benzoic acid is always the product regardless of the starting alkylbenzene.
Oxidative cleavage of alkynes:
Internal and terminal alkynes undergo oxidative cleavage to carboxylic acids when treated with ozone followed by water.
Carboxylation of organometallic reagents:
- Nucleophilic attack of the organometallic reagent on the carbon dioxide to form a carboxylate ion.
- Protonation of the carboxylate ion to form a carboxylic acid
These 2 steps occur separately because the proton source is incompatible with the organometallic reagent.
Reduction of Carboxylic Acids
Reduction with lithium aluminium hydride:
- Deprotonation of the carboxylic acid to form a carboxylate ion.
- Reaction of the carboxylate ion with AlH3 to form an aldehyde.
- Nucleophilic attack of the hydride on the aldehyde to form an alkoxide.
- Protonation of the alkoxide to form an alcohol.
Reduction with borane (BH3):
Borane reacts selectively with a carboxylic acid moiety in the presence of another carbonyl group ⇒ reduction with borane is often preferred over reduction with LiAlH4.
Check your knowledge about this Chapter
Carboxylic acids are named according to the IUPAC nomenclature by identifying the longest carbon chain that includes the carboxyl group (COOH). This chain is named by replacing the -ane ending of the corresponding alkane with -oic acid. If there are substituents on the carbon chain, their positions are indicated by numbers, with the carboxyl carbon as carbon 1. Functional groups attached to the carbon chain are named as prefixes, and the carboxyl group has the highest priority.
The key physical properties of carboxylic acids include their high boiling points relative to other similar sized organic molecules, which result from their ability to form strong hydrogen bonds. Carboxylic acids are also known for their distinctive, often sharp odors; acetic acid, for instance, is the main component of vinegar's smell. These compounds are generally more soluble in water than alkanes or ethers of comparable molecular weight, due to their ability to participate in hydrogen bonding with water molecules. As the length of the hydrocarbon chain increases, the solubility in water decreases, and the solubility in nonpolar solvents increases.
Carboxylic acids exhibit high solubility in water due to their ability to form hydrogen bonds with water molecules. Each carboxylic acid molecule has both a carbonyl (C=O) group and a hydroxyl (OH) group that can participate in hydrogen bonding. The hydroxyl hydrogen acts as a hydrogen bond donor, while the carbonyl oxygen acts as a hydrogen bond acceptor.
Because water molecules can act both as hydrogen bond donors and acceptors, they are able to effectively solvate carboxylic acid molecules, leading to increased solubility. This strong intermolecular interaction is responsible for the relatively high boiling points of carboxylic acids compared to hydrocarbons of similar molecular weight.
The carboxyl group (-COOH) in carboxylic acids is responsible for their acidic behavior because it can donate a proton (H⁺) to a base, leaving behind a resonance-stabilized carboxylate ion (-COO⁻). The resonance stabilization is essential because it delocalizes the negative charge over two oxygen atoms, reducing the energy of the system and increasing the stability of the conjugate base. Hence, a more stable conjugate base equates to a stronger acid, which is why carboxylic acids are stronger acids compared to alcohols and many other organic compounds.
How does the acidity of carboxylic acids compare to other functional groups like alcohols or phenols?
Carboxylic acids are generally more acidic than alcohols or phenols due to the formation of a resonance-stabilized carboxylate anion upon deprotonation. The negative charge can be delocalized over two oxygen atoms in the carboxylate group, enhancing the stability of the anion and favoring the release of the proton. In contrast, the alkoxide ions formed from alcohols and the phenoxide ions from phenols are not as delocalized, making these compounds less acidic.
The pKa value of a carboxylic acid reflects how easily the compound donates a proton (H+), thus showing its strength as an acid. Lower pKa values indicate stronger acids, meaning the carboxylic acid is more likely to donate its proton to a base. In a biochemical context, pKa values are critical for understanding the behavior of carboxylic acids in enzymatic reactions and metabolic pathways, as the state of protonation can affect molecular interactions and reaction mechanisms.
Electron-withdrawing substituents increase the acidity of carboxylic acids by stabilizing the negative charge on the carboxylate anion that forms after deprotonation. These substituents, such as halogens, nitro groups, or cyano groups, pull electron density away from the carboxylate anion through inductive or resonance effects. This results in a more stable anion, which makes the loss of a proton (H+) from the carboxylic acid more favorable, therefore increasing its acidity.
Electron-donating substituents decrease the acidity of carboxylic acids by increasing the electron density on the carboxylic group. The stabilization of the negative charge on the existing carboxylate anion is less favorable, making it harder for the carboxylic acid to donate a proton. Consequently, acids with electron-donating groups have higher pKa values, which indicate weaker acidity.
The inductive effect and resonance are crucial for understanding the acidity of carboxylic acids:
- The inductive effect involves the pull of electron density through σ bonds, which is typically caused by electronegative atoms like chlorine. This effect stabilizes the negative charge on the carboxylate ion formed after deprotonation, increasing the acid's strength.
- Resonance contributes to the stability of carboxylate ion by delocalizing the negative charge over the oxygen atoms, further enhancing the acid's ability to donate a proton.
Both factors lower the pKa, resulting in a stronger acid. Generally, the stronger these effects are, the more acidic the carboxylic acid will likely be.
The common methods for synthesizing carboxylic acids include:
- Oxidation of primary alcohols or aldehydes using oxidizing agents like chromic acid (H2CrO4) or nitric acid (HNO3).
- Oxidation of alkylbenzenes using oxidizing agents like sodium dichromate (Na2Cr2O7) in sulfuric acid (H2SO4).
- Grignard reagents reacting with carbon dioxide (CO2) to form carboxylic acids after hydrolysis.
- Oxidative cleavage of alkynes using strong oxidizing agents such as potassium permanganate (KMnO4) or ozone (O3).
- The hydrolysis of nitriles to carboxylic acids in the presence of acid or base.
Grignard reagents play a crucial role in the synthesis of carboxylic acids by reacting with carbon dioxide. When a Grignard reagent, which is an organomagnesium compound, is exposed to carbon dioxide, it forms a carboxylate anion intermediate. Upon acidic work-up, this intermediate is protonated to yield the respective carboxylic acid, effectively extending the carbon chain by one carbon atom.
What are the reagents and conditions typically used in the reduction of carboxylic acids to alcohols?
The reduction of carboxylic acids to alcohols typically involves the use of reducing agents such as lithium aluminium hydride (LiAlH4) or borane (BH3). These reactions generally occur under anhydrous conditions to prevent the reducing agents from reacting with water. The reduction with LiAlH4 is usually carried out in solvents like diethyl ether or tetrahydrofuran (THF), whereas borane reductions are often conducted in THF or other coordinating solvents.
Why is lithium aluminium hydride preferred over sodium borohydride for the reduction of carboxylic acids?
Lithium aluminium hydride (LiAlH4) is a stronger reducing agent than sodium borohydride (NaBH4), which makes it more effective for the reduction of carboxylic acids to primary alcohols. NaBH4 is generally too mild to reduce carboxylic acids efficiently, as it is more selective and typically used for the reduction of aldehydes and ketones. The robust reactivity of LiAlH4 towards carboxylic acids is attributed to the higher reactivity of the hydride ion (H-) in this reagent, which can readily donate electrons to the carbonyl carbon of the carboxylic acid, leading to the formation of the alcohol.