MCAT Organic Chemistry Review

Carboxylic Acid Derivatives

Answers and Explanations

1.    AMethyl 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.

2.    DThis question asks for the products when ammonia reacts with acetic anhydride. Recall from the chapter that an amide and a carboxylic acid will be formed. However, the carboxylic acid—an acid—is in the same environment as ammonia—a base. The two will react, forming the ammonium carboxylate shown.

3.    AA 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.

4.    CThis question requires knowledge of the nomenclature of cyclic molecules. A δ-lactam, choice (A), has a bond between the nitrogen and the fourth carbon away from the carbonyl carbon. This ring will have six elements: the nitrogen, the carbonyl carbon, and the four carbons in between. Cyclohexane carboxylic acid, choice (B), has cyclohexane, a six-membered cycloalkane. The anhydride formed from pentanedioic acid, choice (D), will have the five carbons in the parent chain and one oxygen atom closing the ring, meaning there are still six elements. γ-butyrolactone will have five elements because it contains a bond between the ester oxygen and the third carbon away from the carbonyl carbon. The five elements will be the oxygen, the carbonyl carbon, and the three carbons in between.

5.    DWith 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.

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

7.    AMethylamine 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.

8.    APropanamide 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.

9.    Dβ-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.

10.CAs far as we can tell, we are converting one ester to another in this reaction. The fact that this reaction is acid-catalyzed should confirm the suspicion that this is a transesterification reaction.

11.BThis 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.

12.DThis molecule is more stable with a positive charge than a straight-chain alkane due to the conjugation of the benzene ring. This permits delocalization of the charge through resonance. Although induction, choice (C), does have an effect on the stabilization of the molecule, this effect is much less significant than the impact of having a conjugated system. The electronegativity of nitrogen, choice (B), which primarily affects induction, is also not a vital component of the stabilization by this molecule of a positive charge because oxygen is more electronegative. Steric hindrance, choice (A), would affect the reactivity of a molecule, but not its ability to stabilize charge.

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

14.AIn order to prepare butyl acetate from butanol, we need to perform a nucleophilic acyl substitution reaction. If the product is an ester, we need to start with a reactant that is more reactive than the ester itself, or the reaction will not proceed. Anhydrides are more reactive than esters, but amides are less reactive, eliminating choices (C) and (D). Reaction with propanoic anhydride, as in choice (B), would result in butyl propanoate.

15.DThe 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.