Primary amines

Primary Amines: Your Essential Study Guide (9701)

Welcome to the fascinating world of Nitrogen Chemistry! This chapter focuses on Amines, which are essentially organic derivatives of ammonia (\(\text{NH}_3\)). They are incredibly important molecules, acting as building blocks for proteins (amino acids), DNA, and many pharmaceuticals and synthetic materials.

Don't worry if organic chemistry sometimes feels like a maze of reactions. We'll break down the structure, synthesis, and key chemical property (basicity) of primary amines into clear, manageable steps!

1. Structure, Classification, and Nomenclature

1.1 What is an Amine?

An amine is a compound where one or more hydrogen atoms in the ammonia molecule (\(\text{NH}_3\)) have been replaced by an alkyl or aryl group.

The nitrogen atom in all amines possesses a crucial feature: a lone pair of electrons. This lone pair makes amines:

• Strong Nucleophiles (electron-pair donors, seeking positive centres).
• Weak Bases (proton acceptors, key to their chemical behaviour).

1.2 Classification of Amines (Primary, Secondary, Tertiary)

Amines are classified based on how many alkyl groups (R) are attached directly to the nitrogen atom:

Primary Amines (1°):
The nitrogen atom is attached to one alkyl group and two hydrogen atoms.
Formula: \(\text{R}-\text{NH}_2\)
Example: Ethylamine (\(\text{CH}_3\text{CH}_2\text{NH}_2\))

Secondary Amines (2°):
The nitrogen atom is attached to two alkyl groups and one hydrogen atom.
Formula: \(\text{R}_2\text{NH}\) or \(\text{R}-\text{NH}-\text{R}'\)
Example: Dimethylamine (\(\text{CH}_3\text{NHCH}_3\))

Tertiary Amines (3°):
The nitrogen atom is attached to three alkyl groups and no hydrogen atoms.
Formula: \(\text{R}_3\text{N}\)
Example: Trimethylamine (\((\text{CH}_3)_3\text{N}\))

Memory Aid for Classification:

Think about how many C-N bonds there are, not how many C atoms are in total!

• 1° Amine = 1 C-N bond
• 2° Amine = 2 C-N bonds
• 3° Amine = 3 C-N bonds

1.3 Nomenclature (Naming Primary Amines)

Primary aliphatic amines are usually named by taking the name of the alkyl group (R) and adding the suffix -amine.

• \(\text{CH}_3\text{CH}_2\text{NH}_2\) is Ethylamine.
• \(\text{CH}_3\text{CH}_2\text{CH}_2\text{NH}_2\) is Propylamine or Propan-1-amine.

2. Synthesis of Primary and Secondary Amines

The syllabus requires you to know three main methods for producing primary amines (from halogenoalkanes, nitriles, or amides) as well as the preparation of secondary amines.

2.1 Method 1: Reaction of Halogenoalkanes with Ammonia

This is a standard nucleophilic substitution reaction where the nucleophile, ammonia (\(\text{NH}_3\)), attacks the partially positive carbon atom (\(\delta+\text{C}\)) bonded to the halogen.

Reagents: Halogenoalkane (\(\text{R-X}\)) and Ammonia (\(\text{NH}_3\)).
Conditions: In ethanol (solvent), heated under pressure (in a sealed tube).

Step-by-Step Reaction:

1. The ammonia nucleophile attacks the carbon:
\(\text{R}-\text{X} + \text{NH}_3 \rightarrow \text{R}-\text{NH}_3^+ \text{X}^-\) (an alkylammonium salt)

2. Excess ammonia then removes a proton from the salt to form the amine:
\(\text{R}-\text{NH}_3^+ \text{X}^- + \text{NH}_3 \rightarrow \text{R}-\text{NH}_2 + \text{NH}_4^+ \text{X}^-\) (where \(\text{NH}_4^+ \text{X}^-\) is ammonium salt)

Formation of Secondary Amines and Polysubstitution:

The product, the primary amine (\(\text{RNH}_2\)), is also a nucleophile. It can react further with remaining halogenoalkane in ethanol under pressure to form a secondary amine:

\(\text{R}-\text{X} + \text{R}'\text{NH}_2 \rightarrow \text{R}-\text{NH}-\text{R}' + \text{HX}\)

To synthesise predominantly primary amines, use a large excess of ammonia to minimize further substitution.

2.2 Method 2: Reduction of Nitriles

This method is excellent because it reliably produces only the primary amine and also increases the carbon chain length by one carbon atom (the carbon from the nitrile group, \(\text{-CN}\)).

Starting Material: Nitrile (\(\text{R}-\text{C}\equiv\text{N}\)).
Reagents/Conditions (Two options):

• Option A (Strong Reducing Agent): Lithium aluminium hydride (\(\text{LiAlH}_4\)) in dry ether, followed by aqueous acid.
• Option B (Catalytic Hydrogenation): Hydrogen gas (\(\text{H}_2\)) over a nickel (\(\text{Ni}\)) catalyst and heat.

General Equation (using \([\text{H}]\) for reduction):
\(\text{R}-\text{C}\equiv\text{N} + 4[\text{H}] \rightarrow \text{R}-\text{CH}_2\text{NH}_2\)

Example: The reduction of propanenitrile yields propylamine (or propan-1-amine). Notice the new \(\text{CH}_2\) group is formed where the triple bond was.

2.3 Method 3: Reduction of Amides

Amides contain the \(\text{RCONH}_2\) functional group. They can be reduced to primary amines using a very powerful reducing agent.

Starting Material: Primary Amide (\(\text{RCONH}_2\)).
Reagent: Lithium aluminium hydride (\(\text{LiAlH}_4\)) in dry ether followed by dilute acid.

Analogy: Imagine the oxygen atom (\(\text{C=O}\)) is simply swapped for two hydrogen atoms (\(\text{CH}_2\)).

General Equation:
\(\text{RCONH}_2 + 4[\text{H}] \rightarrow \text{RCH}_2\text{NH}_2 + \text{H}_2\text{O}\)

Key Takeaway from Synthesis: Reduction of nitriles and amides gives pure primary amines, avoiding the mixture of products obtained from halogenoalkanes and ammonia.

3. Chemical Properties of Amines: Basicity

Primary amines are known for their basic nature. This is a crucial concept, and you must be able to describe and explain the relative basicities of aqueous amine solutions.

3.1 Amines as Brønsted-Lowry Bases

A Brønsted-Lowry Base is a proton (\(\text{H}^+\)) acceptor. The nitrogen lone pair enables the amine to accept a proton, forming an alkylammonium ion (\(\text{RNH}_3^+\)).

When dissolved in water, an amine establishes an equilibrium, reacting with water to produce hydroxide ions (\(\text{OH}^-\)). This presence of hydroxide ions makes the solution alkaline.

Equilibrium Reaction:
\(\text{RNH}_2(aq) + \text{H}_2\text{O}(l) \rightleftharpoons \text{RNH}_3^+(aq) + \text{OH}^-(aq)\)

The position of this equilibrium determines the strength of the base. The further the equilibrium shifts to the right (producing more \(\text{OH}^-\)), the stronger the base.

3.2 Explaining Relative Basicities: Primary Alkylamines, Ammonia, and Phenylamine

The relative order of base strength in aqueous solution is:
Primary alkylamine (e.g. ethylamine) > Ammonia (\(\text{NH}_3\)) > Phenylamine (\(\text{C}_6\text{H}_5\text{NH}_2\))

1. Alkylamines vs. Ammonia (Positive Inductive Effect)

• Alkyl groups (e.g. ethyl, methyl) are electron-releasing groups with a positive inductive effect (+I).
• They push electron density onto the nitrogen atom, increasing the electron density of the nitrogen lone pair.
• This makes the lone pair more available to accept a proton (\(\text{H}^+\)).
• Therefore, primary alkylamines are stronger bases than ammonia.

2. Ammonia vs. Phenylamine (Delocalisation Effect)

• In phenylamine (\(\text{C}_6\text{H}_5\text{NH}_2\)), the lone pair of electrons on the nitrogen atom overlaps with the delocalised \(\pi\)-system of the benzene ring.
• This delocalisation decreases the electron density on the nitrogen atom.
• As a result, the lone pair on nitrogen is much less available to accept a proton (\(\text{H}^+\)).
• Therefore, phenylamine is a significantly weaker base than ammonia.

4. Reaction with Acyl Chlorides: Formation of Amides

Primary amines are highly reactive nucleophiles and react readily with acyl chlorides (like ethanoyl chloride) in an example of a condensation reaction (nucleophilic addition-elimination).

4.1 Formation of N-Substituted Amides

When an amine reacts with an acyl chloride, an amide is formed, specifically an N-substituted amide, along with hydrogen chloride gas (\(\text{HCl}\)).

Reagents: Primary amine (\(\text{RNH}_2\)) and Acyl chloride (\(\text{R}'\text{COCl}\)).
Conditions: Room temperature.

General Equation:
\(\text{R}'\text{COCl} + \text{RNH}_2 \rightarrow \text{R}'\text{CONHR} + \text{HCl}\)

Example: Reaction of ethylamine with ethanoyl chloride.
\(\text{CH}_3\text{COCl} + \text{CH}_3\text{CH}_2\text{NH}_2 \rightarrow \text{CH}_3\text{CONHCH}_2\text{CH}_3 + \text{HCl}\)

The product, \(\text{CH}_3\text{CONHCH}_2\text{CH}_3\), is named N-ethylethanamide. (The N- prefix indicates the ethyl group is attached to the nitrogen atom).

Step-by-Step Mechanism Context:

1. The primary amine (\(\text{RNH}_2\)), acting as a nucleophile via its lone pair, attacks the electron-deficient carbonyl carbon (\(\text{C=O}\)) of the acyl chloride.
2. A tetrahedral intermediate forms.
3. The chloride ion (\(\text{Cl}^-\)) is eliminated and a proton (\(\text{H}^+\)) is lost from nitrogen, yielding the N-substituted amide and \(\text{HCl}\).

This reaction is rapid and vigorous at room temperature because acyl chlorides are highly reactive compounds.