Amines

Question 1

Define:

amine

Answer 1

It is an organic molecule derived from ammonia (NH₃) in which one or more hydrogen atoms has been replaced with a carbon chain.

To name an amine, remove the “-e” from the name of the parent alkane and replace it with “-amine.”

Question 2

When is the prefix “amino-“ used to name an amine?

Answer 2

This is used to name an -NH₂ group as a substituent when the molecule contains higher-priority groups.

For example, alcohols and carboxylic acids take priority over amines.

“Amino-“ is also used as a prefix when the -NH₂ group is located on a non-terminal carbon.

Question 3

What is the name of this molecule?

Answer 3

butanamine

To name an amine in which the NH₂ group is on a terminal carbon, simply replace the “-e” of the parent alkane chain with “-amine.”

Question 4

What is the name of this molecule?

Answer 4

2-aminopropanol

The highest-priority group on this carbon chain is the -OH. Therefore, the molecule should be named as an alcohol and given the “-ol” ending. The “amino-“ prefix is used to denote the -NH₂ group as a substituent on the chain.

Question 5

When can an amine’s nitrogen atom be chiral?

Answer 5

A nitrogen can have chirality if it is bound to either three or four asymmetric groups.

Tertiary amines invert spontaneously at room temperature and exist as a racemic mixture. Quaternary amines do not invert and thus maintain their chirality.

Question 6

Is the following molecule chiral, and will a solution of it at room temperature be optically active?

Answer 6

It is chiral. However, it will not be optically active in solution.

This molecule is a tertiary amine bound to three different groups, so it is chiral. Tertiary amines spontaneously invert at room temperature, making a solution of this molecule racemic and not optically active.

Question 7

What is the strongest type of intermolecular attraction that can be exhibited by an amine?

Answer 7

hydrogen bonds

Hydrogen bonding increases the boiling and melting points of amines relative to those of alkanes.

Question 8

How do the boiling points of amines compare to those of alcohols?

Assume all compounds have similar molecular weight, chain length, and branching.

Answer 8

Amines tend to have lower boiling points than those of analogous alcohols.

This trend exists because alcohols exhibit stronger hydrogen bonding and thus have higher intermolecular forces.

Question 9

How do the melting points of amines compare to those of alkanes?

Assume all compounds have similar molecular weight, chain length, and branching.

Answer 9

Amines tend to have higher melting points than those of analogous alkanes.

This trend exists because amines can hydrogen bond, while alkanes cannot. Hydrogen bonding is a strong intermolecular force, and stronger intermolecular forces increase boiling and melting points.

Question 10

What type of reaction is an amide formation?

Answer 10

Nucleophilic substitution reaction - an amine attacks a carbonyl carbon and displaces a good leaving group.

As shown above, an amine can attack an acyl chloride and displace chlorine, forming an amide.

Question 11

What product will be formed in this reaction?

Answer 11

amide

The reaction shown here is a nucleophilic substitution in which the secondary amine attacks the carbonyl carbon. Chloride, a good leaving group, is displaced.

Question 12

What type of group is added in the acylation of an amine?

Answer 12

An acyl group (RCO) is added to an amine, creating an amide.

This reaction is similar to regular amide formation.

Question 13

What product will be formed in this reaction?

Answer 13

amide

This reaction is an acylation, in which the amine acts as a nucleophile and attacks the acyl chloride. Chloride ion, a good leaving group, is displaced.

Question 14

What type of group is added in the alkylation of an amine?

Answer 14

An alkyl group (R) is added to an amine.

Typically, this reaction will involve nucleophilic substitution, in which an amine attacks an alkyl halide. Alkylations can occur multiple times.

Question 15

How does the alkylation of an amine affect the nucleophilicity of the final product?

Answer 15

Alkylation increases the nucleophilicity of the resulting amine.

This trend occurs because alkyl groups are electron-donating, and the greater the electron density on the nitrogen atom, the more likely it will be to attack electropositive groups.

Question 16

Why do exhaustive alkylations of amines by alkyl halides readily occur?

Answer 16

Since alkylation increases the nucleophilicity of the amine, each subsequent reaction becomes increasingly likely to occur.

The amine will continue to perform nucleophilic attacks on the alkyl halides until the amine is fully alkylated.

Question 17

What product(s) can potentially form in this reaction?

Answer 17

• triethylamine
• diethylamine
• ethylamine

Multiple products can form because multiple alkylations occur. Alkylation increases the nucleophilicity of the amine, resulting in further alkylations whenever possible.

Question 18

Briefly describe what occurs in a Hofmann elimination.

Answer 18

A non-terminal amine is exhaustively methylated. The methylated amine acts as a leaving group in an elimination reaction, forming a double bond.

Question 19

How do Hofmann and Zaitsev eliminations differ?

Answer 19

• In Hofmann elimination, the less substituted double bond is formed.
• In Zaitsev elimination, the more substituted double bond is formed.

Question 20

What product will be formed in this reaction?

Answer 20

• propene
• trimethylamine

The reaction shown is a Hofmann elimination. In the first step, the amine is exhaustively methylated. It is then eliminated, creating a double bond, in the second step.

Question 21

What, if any, acid/base properties does an amine have?

Answer 21

Amines are basic, meaning that they readily gain protons if possible.

Ammonia, NH₃, is a weak base that commonly appears on the MCAT. NH₂^- is also a base, though it is much stronger.

Question 22

What product will form when an amine is reacted with a weak base?

Answer 22

nothing

Amines are basic and are not readily deprotonated, so they are unlikely to react with a weak base. However, since they are easily protonated, they would react with an acid.

Question 23

What properties of an amine’s substituents can affect its basicity?

Answer 23

1. The electron-donating or withdrawing nature of substituents on the amine
2. The solvability of the amine in its protonated form
3. The steric hindrance of the substituents on the amine

Question 24

How does an alkyl substituent affect the basicity of an amine?

Answer 24

These increases the basicity of amines because alkyl groups are electron donors.

Electron-donating groups increase an amine’s electron density, making it more prone to accept a proton. On the other hand, electron-withdrawing groups decrease basicity. The opposite of this trend is true for acidity.

Question 25

How is the basicity of an amine affected by the solvation of its conjugate acid?

Answer 25

Increased solvation of the conjugate acid increases the basicity.

Solvation disperses the positive charge of the protonated amine, making that conjugate base more stable. A more stable conjugate increases the basicity of the original amine. In general, better solvation occurs when fewer alkyl substituents are present because the nitrogen is more able to hydrogen bond with water.

Question 26

How does a bulky substituent affect the basicity of an amine?

Answer 26

These decreases basicity because steric hindrance impairs the amine’s ability to accept a proton.

Question 27

What effect does an amine group have on the stability of adjacent carbocations?

Answer 27

It stabilize adjacent carbocations by donating electron density from the nitrogen atom’s lone pair electrons.

In general, amines are able to stabilize any positive group.

Question 28

Why might the carbocation shown below be especially stable?

Answer 28

The carbocation’s stability is increased by the adjacent amine functionality.

The resonance structure above depicts how this occurs: the amine nitrogen donates its lone pair electrons to the carbocation, decreasing its reactivity.

Question 29

Briefly explain the steps involved in imine formation.

Answer 29

1. Nucleophilic attack: The amine attacks the carbonyl carbon, forming a tetrahedral intermediate.
2. Proton transfer: Proton transfers stabilize the intermediate, forming a carbinolamine (a hydroxyl and amine on the same carbon).
3. Dehydration: Loss of water occurs, leading to the formation of a double bond between the carbon and nitrogen.
4. Proton transfer: Final adjustments stabilize the imine structure.

The carbonyl oxygen leaves as water and the attacking nitrogen forms a double bond with the carbonyl carbon.

Question 30

What product will form in this reaction?

Answer 30

• imine
• water (as a side product)

The primary amine attacks the carbonyl carbon, causing the oxygen atom to leave as water. The nitrogen forms a double bond with the carbonyl carbon.