Organic Chemistry 101: Amines

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.”

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.

butanamine

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.

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.

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.

hydrogen bonds

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

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.

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.

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.

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.

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

This reaction is similar to regular amide formation.

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.

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.

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.

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.

• triethylamine

• diethylamine

• ethylamine

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

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

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

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

• 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.

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

Ammonia, NH3, is a weak base. NH2- is also a base, though it is much stronger.

Nothing will occur.

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.

Properties that affect basicity include:

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

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.

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.

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

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.

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.

These are formed when a primary amine acts as a nucleophile, attacking the carbonyl carbon in the presence of an acid catalyst.

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

• 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.