Test: Carboxylic Acid Derivatives - MCAT MCQ

Methyl propanoate is an ester; it can be synthesized by reacting a carboxylic acid with an alcohol in the presence of acid. Here, the parent chain is propanoate, and the esterifying group is a methyl group. Choice (B) reverses the nomenclature, and would form propyl methanoate. The other reactions listed would not form esters.

A Fischer esterification involves reacting a carboxylic acid and an alcohol with an acid catalyst. Under these conditions, the carbonyl carbon is open to attack by the nucleophilic alcohol. The rate of this reaction depends on the amount of steric hindrance around the carbonyl carbon because there must be room for the alcohol to approach the carboxylic acid substrate. Choices (B), (C), and (D) all have more crowding around the carbonyl carbon, which will decrease reactivity. The additional alkyl groups in these other choices also donate electron density to the carbonyl carbon, making it slightly less electrophilic.

With the same R groups, steric influence is the same in each case, so we can therefore rely solely on electronic effects. When this is all that is taken into account, reactivity toward nucleophiles is highest for anhydrides, followed by esters and carboxylic acids, then amides.

Methylamine would react readily to form an amide. The less substituted the nucleophile, the easier it will be for the nucleophile to attack the carbonyl carbon and form the amine. In fact, triethylamine choice (B), would not be able to form an amide at all because it does not have a hydrogen to lose while attaching to the carbonyl carbon.

β-lactams are amides in the form of four-membered rings; amides are generally the least reactive type of carboxylic acid derivative. β-lactams experience significant ring strain from both eclipsing interactions (torsional strain) and angle strain, and are therefore more susceptible to hydrolysis than the linear form of the same molecule.

This reaction, which is the hydrolysis of an amide, is favored in catalytic acid. Acid protonates the carbonyl oxygen, which increases the electrophilicity of the carbonyl carbon. This allows water to serve as the nucleophile, attacking the bond and hydrolyzing the molecule.

The molecule shown, γ-nonalactone, is a cyclic ester, also called a lactone. This molecule could arise from intramolecular attack in a γ-hydroxycarboxylic acid.

The presence of water in an esterification would likely revert some of the desired esters back into carboxylic acids. Small carboxylic acids, like formic or acetic acid, are easily dissolved in water, eliminating choice (A). The polarity of water plays little role in affecting the leaving group; if anything, water can be used to increase the electrophilicity of the carbonyl carbon by protonating the carbonyl oxygen—eliminating choice (B). Finally, this is a nucleophilic substitution mechanism, not a nucleophilic addition mechanism, as mentioned in choice (C). Further, hydrogen bonding would likely augment the reaction.

Propanamide is an amide; as such, it is the least reactive of the carboxylic acid derivatives discussed in this chapter. Without strong acid or base, propanamide will not be able to undergo nucleophilic acyl substitution and no reaction will occur.

Anhydrides, particularly cyclic anhydrides, will form spontaneously from dicarboxylic acids when heated.