MCAT Organic Chemistry Review

Carboxylic Acids

Conclusion

Acids are an important concept on the MCAT: they can be tested in general chemistry, organic chemistry, and biochemistry. The underlying concept in all three subjects is the same: the more stable the conjugate base is, the more likely it is that the proton will leave. This stability is determined by three factors: periodic trends (electronegativity and, thus, induction), size of the anion, and resonance. Understanding resonance effects is a major key to success on Test Day. The reactions of carboxylic acids, in particular, are dictated by the polarity of the carbonyl group in conjunction with the ability of the hydroxyl group to act as a leaving group. This allows a diversity of reactions through nucleophilic acyl substitution, reduction by lithium aluminum hydride, decarboxylation, and saponification.

Concept Summary

Description and Properties

·        Carboxylic acids contain a carbonyl and a hydroxyl group connected to the same carbon. They are always terminal groups.

·        Carboxylic acids are indicated with the suffix –oic acid. Salts are named with the suffix –oate, and dicarboxylic acids are –dioic acids.

·        Physical Properties

o   Carboxylic acids are polar and hydrogen bond very well, resulting in high boiling points. They often exist as dimers in solution.

o   The acidity of a carboxylic acid is enhanced by the resonance between its oxygen atoms.

o   Acidity can be further enhanced by substituents that are electron-withdrawing, and decreased by substituents that are electron-donating.

o   β-dicarboxylic acids, like other 1,3-dicarbonyl compounds, have an α-hydrogen that is also highly acidic.

Reactions of Carboxylic Acids

·        Carboxylic acids can be made by the oxidation of primary alcohols or aldehydes using an oxidizing agent like potassium permanganate (KMnO4).

·        Nucleophilic acyl substitution is a common reaction in carboxylic acids.

o   A nucleophile attacks the electrophilic carbonyl carbon, opening the carbonyl and forming a tetrahedral intermediate.

o   The carbonyl reforms, kicking off the leaving group.

o   If the nucleophile is ammonia or an amine, an amide is formed. Amides are given the suffix –amide. Cyclic amides are called lactams.

o   If the nucleophile is an alcohol, an ester is formed. Esters are given the suffix –oate. Cyclic esters are called lactones.

o   If the nucleophile is another carboxylic acid, an anhydride is formed. Both linear and cyclic anhydrides are given the suffix anhydride.

·        Carboxylic acids can be reduced to a primary alcohol with a strong reducing agent like lithium aluminum hydride (LiAlH4).

o   Aldehyde intermediates are formed, but are also reduced to primary alcohols.

o   Sodium borohydride (NaBH4) is a common reducing agent for other organic reactions, but is not strong enough to reduce a carboxylic acid.

·        β-dicarboxylic acids and other β-keto acids can undergo spontaneous decarboxylation when heated, losing a carbon as carbon dioxide. This reaction proceeds via a six-membered cyclic intermediate.

·        Mixing long-chain carboxylic acids (fatty acids) with a strong base results in the formation of a salt we call soap. This process is called saponification.

o   Soaps contain a hydrophilic carboxylate head and hydrophobic alkyl chain tail.

o   Soaps organize in hydrophilic environments to form micelles. A micelle dissolves nonpolar organic molecules in its interior, and can be solvated with water due to its exterior shell of hydrophilic groups.

Answers to Concept Checks

·        8.1

1.    Carboxylic acids are particularly acidic due to the electron-withdrawing oxygen atoms in the functional group and the high stability of the carboxylate anion, which is resonance stabilized by delocalization with two electronegative oxygen atoms.

2.    A dicarboxylic acid would be the most acidic, as the second carboxyl group is electron-withdrawing and therefore contributes to even higher stability of the anion after loss of the first hydrogen. However, a monocarboxylic acid is more acidic than a deprotonated dicarboxylic acid because the carboxylate anion is electron-donating and destabilizes the product of the second deprotonation step, resulting in decreased acidity.

3.    Electron-withdrawing substituents make the anion more stable and therefore increase acidity. Electron-donating substituents, on the other hand, destabilize the anion, causing the carboxylic acid to be less acidic. The closer the substituent is to the carboxylic acid on the molecule, the stronger the effect will be.

·        8.2

1.     

Carboxylic Acid Derivative

Formed by Reaction with:

Name of Cyclic Form:

Amide

Ammonia (NH3) or an amine

Lactam

Ester

Alcohol

Lactone

Anhydride

Another carboxylic acid

Anhydride

2.    Nucleophilic acyl substitution is the substitution of an attacking nucleophile for the leaving group of an acyl compound, which includes carboxylic acids, amides, esters, and anhydrides. The nucleophile attacks, opening the carbonyl and forming a tetrahedral intermediate. The carbonyl then reforms, kicking off the leaving group. This reaction is favored by acidic or basic conditions.

3.    Sodium borohydride is not strong enough to reduce carboxylic acids. Lithium aluminum hydride, however, is strong enough, and reduces carboxylic acids to primary alcohols.

4.    1,3-dicarboxylic acids will spontaneously decarboxylate when heated, due to the stable cyclic intermediate step.

Shared Concepts

·        Biochemistry Chapter 1

o   Amino Acids, Peptides, and Proteins

·        Biochemistry Chapter 5

o   Lipid Structure and Function

·        Organic Chemistry Chapter 1

o   Nomenclature

·        Organic Chemistry Chapter 4

o   Analyzing Organic Reactions

·        Organic Chemistry Chapter 6

o   Aldehydes and Ketones I

·        Organic Chemistry Chapter 9

o   Carboxylic Acid Derivatives