Carboxylic Acids | Organic Chemistry 2

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.

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.

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.

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.