Carboxylic Acids and Their Derivatives Help (page 2)

Polyfunctional Carboxylic Acids

Dicarboxylic Acids. [HO₂C(CH₂)n CO₂H] The chemistry of dicarboxylic acids depends on the value of n. For n = 1, decarboxylations can occur upon heating the diacid. When n = 2 or 3, the diacid forms cyclic anhydrides when heated. Longer-chain ??α, ω-dicarboxylic acids usually undergo intermolecular dehydration on heating to form long-chain polymeric anhydrides.

Hydroxyacids: Lactones. Reactions of hydroxycarboxylic acids, HO(CH₂)_nCO₂H, also depend on value of n. In acid solutions, γ-hydroxycarboxylic acid (n = 3) and δ-hydroxycarboxylic acid (n = 4) form cyclic esters (lactones) with five-membered and six-membered rings, respectively. Intramolecular nucleophilic displacements, such as those in lactone formation, have faster reaction rates than intermolecular S_N2 reactions because the latter require two species to collide.

Reactions of Acid Derivatives

The more reactive derivatives are readily converted to the less reactive ones. Because acetic anhydride reacts less violently, it is often used instead of the more reactive acetyl chloride to make derivatives of acetic acid. Since other anhydrides are not readily available, the acid chlorides are used to make acid derivatives. The reactivity order is acid chlorides > anhydrides > ester > amide.

Nucleophilic substitution of acyl compounds takes place readily if the incoming group (Nu:^– or Nu:) is a stronger base than the leaving group (G:^–) or if the final product is a resonance-stabilized RCO₂^–.

The reactions of acid derivatives generally involve nucleophilic attack at the carbonyl carbon. Nucleophilic substitutions of RCOG, such as RCOCl, occur in two steps. The first step (addition) resembles nucleophilic addition to ketones and aldehydes and the second step (elimination) is loss of G, in this case, Cl^–.

Reactions of this type can be carried out either in acid or in base. For example, in hydrolysis, the protonation of carbonyl O makes C more electrophilic and hence more reactive toward weakly nucleophilic H₂O. Strongly basic ^–OH readily attacks the carbonyl C. Unlike acid hydrolysis, this reaction is irreversible, because ^–OH removes H⁺ from RCO₂H to form resonance-stabilized RCO₂^–.

Acid Chlorides. Acid chlorides are used in Friedel-Craft acylations of benzene rings with AlCl₃ catalyst, discussed in Chapter 7. They are also readily converted to other acid derivatives by reaction with the appropriate nucleophile.

Acid Anhydrides. Heating dicarboxylic acids, HO₂(CH₂)_nCO₂H (n = 2 or 3), forms cyclic anhydrides by intramolecular dehydration. Intermolecular dehydration of carboxylic acids is used to prepare acetic anhydride, but other anhydrides are not readily formed using this method. Although they are less reactive than acid chlorides, anhydrides resemble acid halides in their reactions. Acid anhydrides can also be used to acylate aromatic rings in electrophilic substitutions.

Esters. Esters react more slowly than acid chlorides or anhydrides. They can be used to prepare amides by reaction with an amine. Reduction of esters with LiAlH₄ gives alcohols, as discussed in Chapter 9.

Fats and Oils. Fats and oils are mixtures of esters of glycerol, HOCH₂CHOHCH₂OH, with acyl groups from carboxylic acids, usually with long carbon chains. These triacylglycerols, also called triglycerides, are types of lipids because they are naturally occurring and soluble only in nonpolar solvents. The acyl groups may be identical, or they may be different.

Amides. Unsubstituted amides may be prepared by careful partial hydrolysis of nitriles. Amides are slowly hydrolyzed under either acidic or basic conditions.

Imides. The hydrogen on N of the imides is acidic because the negative charge on N of the conjugate base is delocalized to each O of the two C=O groups, thereby stabilizing the anion.

Practice problems for these concepts can be found at: 

Carboxylic Acids and Their Derivatives Practice Problems