MCAT Organic Chemistry Chapter 9 Carboxylic Acid Derivatives

Amides, esters, and anhydrides are all carboxylic acid derivatives. Each of these is formed by a ______________ reaction with a carboxylic acid - a reaction that combines two molecules into one, while losing a small molecule

condensation

Amides are compounds with the general formula ________________

RCONR2

Amides are named by replacing the -oic acid suffix with ___________

amide

Alkyl substituents on the nitrogen atoms are listed as prefixes, and their location is specified with the letter ___________

N

N-ethyl-Nmethylbutanamide

N,N-dimethylethanamide

N-methylpropanamide

How are amides synthesized?

Reaction of carb acid with ammonia or amide

The loss of hydrogen from the nucleophile is required for amides to be formed. Therefore only _________ and ___________ amides can undergo this reaction

Primary; secondary

cyclic amides are called

lactams

beta lactam

Gamma Lactam

Amides boiling points may be ____________or the same as carb acids

lower

Esters are the ______________ synthesis products of other carboxylic acids derivatives and alcohols.

dehydration

Esters are named by placing the _______________ group (the substituent bonded to the oxygen as a prefix

esterifying

For esters, the suffix _____________ replaces -oic acid

oate

ethyl ethanoate

isopropyl butanoate

Under acidic conditions, mixtures of carboxylic acids and alcohols will condense into _________________. This is called _______________ esterification

esters; Fischer

Cyclic esters

lactones

alpha-acetolactone

beta-propiolactone

gamma-butyrolactone

Because esters lack hydrogen bonding, esters usually have _____________ boiling points than their related carboxylic acids

lower

Storage form of fats inside the body

triacyclglycerols

Triacyclglycerols are _____________ of long chain carboxylic acids and glycerol

esters

Process by which fats are hydrolyzed under basic conditions to produce soap

Saponification

Anhydrides are also called what?

acid anhydrides

Condensation dimers of carboxylic acids

anhydrides

Symmetrical anhydrides are named by substituting the word anhydride for the word ___________ in a carboxylic acid

acid

When anhydrides are asymmetrical, simply name the two chains alphabetically, followed by _______________

anhydride

ethanoic propanoic anhydride

ethanoic anhydride

phthalic anhydride

succinic anhydride

A molecule of ________ is lost in the formation of anhydrides

water

Certain cyclic anhydrides can be formed simply by ____________ carboxylic acids

heating

For anhydride formation, the hydroxyl group acts as the ________________, attacking the carbonyl on the other -COOH

nucleophile

Anhydrides often have _____________ boiling points than their related carboxylic acids, based solely on their much greater weight

Higher

Amides are formed from -COOH by what? Suffix? Cyclic naming?

Ammonia/Amines

Amide

Lactam

Esters are formed from -COOH by what? Suffix? Cyclic naming?

Alcohols

-Oate

Lactone

Anhydrides are formed from -COOH by what? Suffix? Cyclic naming?

Another carboxylic acid

Anhydride

Anhydride

What is the definition of a condensation reaction?

Two molecules joined together by the loss of a water molecule.

List these functional groups in order from most to least reactive:

Anhydride

Amide

Ester

Most: Anhydride

Middle: Ester

Least: Amide

Which functional group (out of anhydrides, esters and amides) is the most electrophilic>

electrophilic

What is steric hinderance?

Describes when a reaction does not proceed due to the size of the substituents

What is induction?

Distribution of charge across sigma bonds

What is conjugation?

Refers to the presence of alternating single and double bonds

In carbonyl containing compounds, conjugation can be established with the carbonyl group itself. alpha-beta unsaturated carbonyls, or __________________, are common examples

enones

Why are beta-lactams prone to hydrolysis?

they have significant ring strain

Ring strain in beta lactams is increased by what?

fusion to a second ring

Protecting groups, such as ________________, can be used to increase steric hinderance or otherwise decrease the reactivity of a rxn

acetal

_____________ refers to the uneven distribution of charge across a sigma bond because of differences in electronegativity.

Induction

______________ refers to the presence of alternating single and multiple bonds, which creates delocalized pi electron clouds above and below the plane of the molecule.

Conjugation

Electrons experience ___________ through unhybridized p-orbitals, increasing stability.

Resonance

Rank the following molecules by decreasing reactivity to OR-; acetamide, acetic anhydride, and ethyl acetate

1. Acetic anhydride

2. Ethyl acetate

3. Acetamide

What is responsible for the increased rate of hydrolysis in beta-lactams?

ring strain

What properties account for differences in reactivity seen between anhydrides, esters, and amides with nucleophiles?

Differences in resonance, steric hinderance, and induction

all carboxylic acid derivatives can undergo what kind of reaction?

nucleophilic substitution reactions

Anhydrides can be cleaved by the addition of a __________________

nucleophile

Addition of ammonia or an amine results in an _________ and a carboxylic acid

amide

Addition of an alcohol results in an ___________ and a carboxylic acid

ester

Addition of water results in two ____________ ______________

carboxylic acids

What is transesterification?

Exchange of one esterifying group for another on an ester.

For esterification, the attacking nucleophile is an ________________

alcohol

Amides can be hydrolyzed to carboxylic acids under strongly _______________ or _______________ conditions. The attacking nucleophile is water or the _________________ anion.

acidic; basic; hydroxide.

In the formation of an amide from ammonia and an anhydride, what serves as the nucleophile? The electrophile?

Nucleophile: Ammonia

Electrophile: Anhydride

What are the products of the transesterification reaction between isopropyl butanoate and ethanol?

Transesterification is the exchange of one esterifying group for another in an ester. This reaction requires an alcohol as a nucleophile. In this case, the ethyl group of ethanol will replace the isoproyl group of isopropyl butanoate, resulting in ethyl butanoate and 2-propanol.

How do strongly acidic and strongly basic conditions catalyze the hydrolysis of an amide?

Strongly acidic conditions catalyze amide hydrolysis by protonating the oxygen in the carbonyl. This increases the electrophilicity of the carbon, making it more susceptible to nucleophilic attack. Strongly basic conditions greatly increase the concentration of OH-, which can act as a nucleophile on amide carbonyls.

Which of the following would be the best method of producing methyl propanoate?

A. Reacting propanoic acid and methanol in the presence of a mineral acid

B. Reacting methanoic acid and propanol in the presence of a mineral acid

C. Reacting propanoic anhydride with an aqueous base

D. Reacting propanoic acid with an aqueous base

A

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.

Each of the acyl compounds listed below contains a six-membered ring EXCEPT:

A. δ-lactam.

B. cyclohexane carboxylic acid.

C. γ-butyrolactone.

D. the anhydride formed from intramolecular ring closure of pentanedioic acid.

C

This 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.

Which of the following would be most reactive toward nucleophiles?

A. Propyl ethanoate

B. Propanoic acid

C. Propanamide

D. Propanoic anhydride

D

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.

How might succinic anhydride, shown below, be formed from succinic acid (butanedioic acid)?

A. Catalytic acid

B. Catalytic base

C. Heat

D. Oxidation

C

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

Which of the following would react most readily with a carboxylic acid to form an amide?

A. Methylamine

B. Triethylamine

C. Diphenylamine

D. Ethylmethylamine

A

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.

If propanamide were treated with water, what product(s) would be observed?

A. Propanamide

B. Propanoic acid

C. Equal concentrations of propanamide and propanoic acid

D. Propyl propanoate

A

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.

β-lactams are:

I. cyclic forms of the least reactive type of carboxylic acid derivative.

II. more reactive than their straight-chain counterparts.

III. molecules with high levels of ring strain.

A. I only

B. II only

C. II and III only

D. I, II, and III

D

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.

The acid-catalyzed conversion of propyl ethanoate to benzyl ethanoate is likely:

A. reduction.

B. hydrolysis.

C. transesterification.

D. oxidation.

C

As 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.

A positive charge on the molecule shown would have greater stability than a positive charge on a straight-chain alkane version of the same molecule. What property most explains this effect?

D

This 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.

Which reactant could be combined with butanol to form butyl acetate?

A. (CH3CO)2O and catalytic acid

B. (CH3CH2CO)2O and catalytic acid

C. CH3CH2CONH2 and catalytic acid

D. CH3CONH2 and catalytic acid

A

In 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.

Why should esterification reactions NOT be carried out in water?

A. Carboxylic acids, from which esters are made, are generally insoluble in water.

B. The polar nature of water overshadows the polar nature of the leaving group.

C. The extensive hydrogen bonding of water interferes with the nucleophilic addition mechanism.

D. Water molecules would hydrolyze the desired products back into the parent carboxylic acid.

D

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