Nitrogen compounds (A Level only)

A-Level Chemistry (9701) Study Notes: Nitrogen Compounds

Hello future Chemists! This chapter takes us into the fascinating world of organic compounds containing nitrogen. These molecules are essential—they form the basis of proteins, dyes, and many pharmaceuticals. Don't worry if the sheer number of reactions seems overwhelming; we will break them down into digestible functional groups (amines, nitriles, amides, and amino acids) and focus only on the specific reactions required by the A-Level syllabus. Let’s dive in!

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1. Amines: The Organic Bases (\(\text{R-NH}_2\))

Amines are derivatives of ammonia (\(\text{NH}_3\)) where one or more hydrogen atoms are replaced by alkyl (R) groups. They are characterised by the presence of a lone pair of electrons on the nitrogen atom, which makes them excellent nucleophiles and bases.

1.1 Classification of Amines

Although detailed classification is not heavily examined, knowing the difference helps explain reactivity:

• Primary Amine: One alkyl group attached to N (\(\text{RNH}_2\)). Example: Ethylamine (\(\text{CH}_3\text{CH}_2\text{NH}_2\)).
• Secondary Amine: Two alkyl groups attached to N (\(\text{R}_2\text{NH}\)).
• Tertiary Amine: Three alkyl groups attached to N (\(\text{R}_3\text{N}\)).

1.2 Preparation of Primary and Secondary Amines

Route A: From Halogenoalkanes (Nucleophilic Substitution)

This is the standard laboratory preparation, starting from a halogenoalkane (RX):

1. Primary Amine Formation:
Halogenoalkane reacts with excess ammonia.
Reagent: Concentrated \(\text{NH}_3\) dissolved in ethanol.
Conditions: Heated under pressure (in a sealed tube).

\(\text{R-X} + 2\text{NH}_3 \longrightarrow \text{R-NH}_2 + \text{NH}_4\text{X}\)

⚠️ Common Mistake Alert: We must use excess \(\text{NH}_3\). If we don't, the primary amine produced (\(\text{RNH}_2\)) is also a nucleophile and can react further with \(\text{R-X}\) to form secondary and tertiary amines, leading to a mixture of products.

2. Secondary Amine Formation:
If you use a primary amine instead of ammonia, you form a secondary amine (requires halogenoalkane + primary amine, in ethanol, heated under pressure in a sealed tube).

Route B: From Nitriles (Reduction)

This route is excellent because it increases the carbon chain length by one carbon atom, which is often crucial in organic synthesis.

Step 1: Making the Nitrile (covered in Halogenoalkanes chapter):
Halogenoalkane reacts with potassium cyanide (\(\text{KCN}\)).
Reagents: \(\text{KCN}\) in ethanol.
Conditions: Heat.

\(\text{R-X} + \text{KCN} \longrightarrow \text{R-CN} + \text{KX}\)

Step 2: Reducing the Nitrile to Amine:
The nitrile is reduced to a primary amine (\(\text{RCH}_2\text{NH}_2\)).
Reagents: Lithium aluminium hydride (\(\text{LiAlH}_4\)) in dry ether, followed by dilute acid; OR Hydrogen gas (\(\text{H}_2\)) with a Nickel (\(\text{Ni}\)) catalyst.

\(\text{R-C}\equiv\text{N} + 4[\text{H}] \longrightarrow \text{RCH}_2\text{NH}_2\)

Route C: From Amides (Reduction)

Amides can be reduced directly to primary amines.
Reagents: Lithium aluminium hydride (\(\text{LiAlH}_4\)) in dry ether.

\(\text{RCONH}_2 + 4[\text{H}] \longrightarrow \text{RCH}_2\text{NH}_2 + \text{H}_2\text{O}\)

1.3 Basicity of Amines (Aqueous Solutions)

Amines are bases because the nitrogen atom has a lone pair of electrons that can accept a proton (\(\text{H}^+\)).

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

The position of equilibrium determines the strength of the base (more \(\text{OH}^-\) produced means stronger base). We must compare the basicity of three key nitrogen compounds:

1. Ethylamine (\(\text{CH}_3\text{CH}_2\text{NH}_2\) - Primary aliphatic amine)
2. Ammonia (\(\text{NH}_3\))
3. Phenylamine (\(\text{C}_6\text{H}_5\text{NH}_2\) - Aromatic amine)

The Order of Basicity:

Ethylamine > Ammonia > Phenylamine

Explanation:

1. Ethylamine (Strongest Base): The ethyl group (\(\text{C}_2\text{H}_5\)) is an electron-donating group. This group pushes electron density onto the nitrogen atom, making the lone pair more available to accept a proton (\(\text{H}^+\)).
2. Ammonia: Acts as a benchmark, having neither a donating nor withdrawing group.
3. Phenylamine (Weakest Base): The benzene ring is an electron-withdrawing group. The lone pair on the nitrogen atom becomes delocalised (or partially absorbed) into the \(\pi\)-system of the benzene ring. This reduces the electron density on the nitrogen, making the lone pair less available to accept a proton, resulting in a much weaker base.

Did you know? The difference in basicity is huge! Phenylamine is so much weaker than ammonia that it barely reacts with water, while ethylamine is a much stronger alkali than ammonia.

1.4 Reaction of Amines with Acyl Chlorides

Amines (or ammonia) react quickly with acyl chlorides (\(\text{R'COCl}\)) at room temperature. This is a condensation reaction (specifically, an addition-elimination reaction) resulting in the formation of an amide and hydrogen chloride (\(\text{HCl}\)).

Reaction with Ammonia:

\(\text{R'COCl} + 2\text{NH}_3 \longrightarrow \text{R'CONH}_2 + \text{NH}_4\text{Cl}\)

Reaction with Primary Amine:

\(\text{R'COCl} + 2\text{RNH}_2 \longrightarrow \text{R'CONHR} + \text{RNH}_3\text{Cl}\) (Note: two moles of amine are needed because the amine acts as a reactant and also to mop up the \(\text{HCl}\) produced.)

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2. Phenylamine and Azo Compounds

Phenylamine (also known as aniline, \(\text{C}_6\text{H}_5\text{NH}_2\)) is the simplest aromatic amine. Its chemistry involves both the aromatic ring and the amino group.

2.1 Synthesis of Phenylamine (A Multi-step Route)

You must recall this specific two-step synthetic route starting from benzene:

Step 1: Nitration of Benzene
Benzene is converted to nitrobenzene (\(\text{C}_6\text{H}_5\text{NO}_2\)).
Reagents: Concentrated nitric acid (\(\text{HNO}_3\)) and concentrated sulfuric acid (\(\text{H}_2\text{SO}_4\)).
Conditions: Temperature controlled at \(50\text{--}55^\circ\text{C}\) (too high gives di-nitration).

Step 2: Reduction of Nitrobenzene
Nitrobenzene is reduced to phenylamine.
Reagents: Hot Tin (\(\text{Sn}\)) and concentrated hydrochloric acid (\(\text{HCl}\)).
Conditions: Heat under reflux.
The initial product is an ammonium salt (\(\text{C}_6\text{H}_5\text{NH}_3^+\text{Cl}^-\)). This salt is then treated with a strong base (like aqueous \(\text{NaOH}\)) to liberate the free amine, phenylamine.

\(\text{C}_6\text{H}_5\text{NO}_2 + 6[\text{H}] \xrightarrow{\text{Sn/HCl, Heat}} \text{C}_6\text{H}_5\text{NH}_3^+\text{Cl}^- \xrightarrow{\text{NaOH}(\text{aq})} \text{C}_6\text{H}_5\text{NH}_2\)

2.2 Key Reactions of Phenylamine

Reaction 1: Bromination (Electrophilic Substitution)

Phenylamine is extremely reactive towards electrophilic substitution. The amine group (\(-\text{NH}_2\)) is a powerful activating group.

Reagents: Aqueous bromine (\(\text{Br}_2(\text{aq})\)).
Conditions: Room temperature.
Observation: Instantaneous reaction, white precipitate forms.
Product: Substitution occurs immediately at all three activated positions (2, 4, and 6) to form 2,4,6-tribromophenylamine.

Reaction 2: Diazotisation and Azo Dye Formation

This process is the basis of synthetic dye chemistry.

Step 1: Diazotisation
Phenylamine reacts with nitrous acid (\(\text{HNO}_2\)) to form a benzenediazonium salt (\(\text{C}_6\text{H}_5\text{N}_2^+\text{Cl}^-\)).
Reagents: Sodium nitrite (\(\text{NaNO}_2\)) and dilute acid (usually \(\text{HCl}\)), which react to generate nitrous acid: \(\text{NaNO}_2 + \text{HCl} \rightarrow \text{HNO}_2 + \text{NaCl}\).
Conditions: Crucially, the temperature must be kept below \(10^\circ\text{C}\). The diazonium salt is unstable above \(10^\circ\text{C}\).

Step 2a: Reaction with Water (To form Phenol)
If the diazonium salt is warmed with water, unstable nitrogen gas (\(\text{N}_2\)) is lost, forming phenol.

\(\text{C}_6\text{H}_5\text{N}_2^+ + \text{H}_2\text{O} \xrightarrow{\text{Warm}} \text{C}_6\text{H}_5\text{OH} + \text{N}_2 + \text{H}^+\)

Step 2b: Coupling Reaction (Azo Dye Formation)
The diazonium ion acts as a weak electrophile and reacts with a highly activated aromatic compound, typically phenol (in alkaline solution). This reaction, called coupling, forms a brightly coloured azo compound (dye).
The azo group is the characteristic functional group (\(-\text{N}=\text{N}-\)).

\(\text{C}_6\text{H}_5\text{N}_2^+ + \text{C}_6\text{H}_5\text{O}^- \longrightarrow \text{C}_6\text{H}_5\text{-N=N-C}_6\text{H}_4\text{OH} + \text{Cl}^-\)

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3. Nitriles and Hydroxynitriles

Nitriles contain the cyano functional group (\(-\text{C}\equiv\text{N}\)). Hydroxynitriles contain both the hydroxyl (\(-\text{OH}\)) and cyano groups.

3.1 Preparation Routes

Nitriles:

As covered in Section 1.2, nitriles are prepared by reacting a halogenoalkane with \(\text{KCN}\) in ethanol and heat. This adds a carbon atom to the chain.

Hydroxynitriles:

Hydroxynitriles are produced by the nucleophilic addition of hydrogen cyanide (\(\text{HCN}\)) to aldehydes or ketones. This reaction requires \(\text{KCN}\) as a catalyst and heat.

\(\text{RCHO} + \text{HCN} \xrightarrow{\text{KCN, Heat}} \text{RCH}(\text{OH})\text{CN}\) (A hydroxynitrile)

3.2 Hydrolysis of Nitriles

Nitriles can be hydrolysed (broken down by water, typically aided by acid or alkali) to form carboxylic acids. This is another key route for making carboxylic acids, especially those with increased chain length.

Reagents & Conditions:

• Acidic Hydrolysis: Dilute acid (\(\text{H}^+\)) and heat under reflux.
• Alkaline Hydrolysis: Dilute alkali (\(\text{OH}^-\)) and heat, followed by acidification (to convert the resulting carboxylate salt back to the carboxylic acid).

\(\text{R-CN} + 2\text{H}_2\text{O} + \text{H}^+ \xrightarrow{\text{Heat}} \text{RCOOH} + \text{NH}_4^+\) (Acid hydrolysis)

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4. Amides

Amides contain the functional group (\(\text{RCONH}_2\)). They are derived from carboxylic acids where the \(-\text{OH}\) group is replaced by an \(-\text{NH}_2\) or \(-\text{NHR}\) group.

4.1 Preparation of Amides

Amides are prepared by reacting acyl chlorides (\(\text{RCOCl}\)) with ammonia or a primary/secondary amine at room temperature (as detailed in Section 1.4).

4.2 Basicity of Amides (Why are they weak?)

Amides are much weaker bases than amines or ammonia.

Explanation: The nitrogen atom's lone pair is delocalised into the adjacent carbonyl (\(\text{C}=\text{O}\)) \(\pi\)-system. This delocalisation means the lone pair is less localised on the N atom and is therefore much less available to accept a proton (\(\text{H}^+\)).

4.3 Reactions of Amides

1. Hydrolysis

Amides can be hydrolysed back into their constituent carboxylic acid and amine/ammonium salt.
Reagents & Conditions:

• Acidic Hydrolysis: Aqueous acid (\(\text{H}^+\)) and heat \(\rightarrow\) Carboxylic acid and Ammonium/amine salt.
• Alkaline Hydrolysis: Aqueous alkali (\(\text{OH}^-\)) and heat \(\rightarrow\) Carboxylate salt and Amine/ammonia.

2. Reduction

Amides can be reduced to primary amines.
Reagents: Lithium aluminium hydride (\(\text{LiAlH}_4\)) in dry ether.

\(\text{RCONH}_2 + 4[\text{H}] \xrightarrow{\text{LiAlH}_4} \text{RCH}_2\text{NH}_2 + \text{H}_2\text{O}\)

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5. Amino Acids (The Basis of Proteins)

Amino acids are special organic molecules that contain both an acidic carboxyl group (\(-\text{COOH}\)) and a basic amino group (\(-\text{NH}_2\)).

5.1 Acid/Base Properties and Zwitterions

Since amino acids contain both an acid and a base within the same molecule, they are amphoteric (they can act as both acids and bases).

In the solid state or in neutral solution, they exist mostly as a zwitterion.

• A zwitterion is a dipolar ion formed when the proton (\(\text{H}^+\)) from the acidic carboxyl group transfers internally to the basic amino group.
• Structure: The molecule has a positive charge (\(-\text{NH}_3^+\)) and a negative charge (\(-\text{COO}^-\)), giving the overall molecule a net zero charge.

\(\text{H}_2\text{N-CH(R)-COOH} \rightleftharpoons \text{H}_3\text{N}^+-\text{CH(R)}-\text{COO}^-\)

The Isoelectric Point (pI)

The isoelectric point (\(\text{pI}\)) is the specific pH value at which an amino acid exists predominantly as the neutral zwitterion (i.e., the net charge is zero).

5.2 Formation and Hydrolysis of Peptides

Amino acids link together via a condensation reaction (elimination of water) between the carboxyl group of one amino acid and the amino group of another.

• The bond formed is an amide bond, known as a peptide bond in biochemistry.
• Two amino acids joining form a dipeptide; three form a tripeptide, and many form a polypeptide (protein).

\(\text{AA}_1(\text{-COOH}) + \text{AA}_2(\text{-NH}_2) \xrightarrow{\text{Condensation}} \text{AA}_1\text{-CO-NH-AA}_2 + \text{H}_2\text{O}\)

Hydrolysis of Proteins and Peptides

Peptides and proteins can be broken down back into their constituent individual amino acids by hydrolysis of the peptide (amide) bonds.
Reagents & Conditions: Heating with moderately concentrated hydrochloric acid (e.g. \(6\text{ mol dm}^{-3}\text{ HCl}\)) under reflux.

5.3 Electrophoresis (Interpreting Results)

Electrophoresis is a technique used to separate a mixture of amino acids or peptides based on the size and, crucially, the charge of the molecules at a specific pH.

The core principle is: When an electric field is applied across a buffer solution:

• Molecules with a net positive charge (\(\text{H}_3\text{N}^+-\dots-\text{COOH}\)) move towards the cathode (negative electrode).
• Molecules with a net negative charge (\(\text{H}_2\text{N}-\dots-\text{COO}^-\)) move towards the anode (positive electrode).
• Molecules existing as the zwitterion (net zero charge, at the \(\text{pI}\)) remain stationary.

Predicting Movement:

1. If the pH of the buffer is low (Acidic): There is an excess of \(\text{H}^+\). The amino group (\(\text{NH}_2\)) and the carboxylate ion (\(\text{COO}^-\)) accept protons. The overall charge is positive (\(\text{H}_3\text{N}^+-\dots-\text{COOH}\)). The molecule moves to the cathode.
2. If the pH of the buffer is high (Alkaline): There is an excess of \(\text{OH}^-\). The acid group (\(\text{COOH}\)) loses its proton. The overall charge is negative (\(\text{H}_2\text{N}-\dots-\text{COO}^-\)). The molecule moves to the anode.
3. If the pH = pI: Net charge is zero. The molecule remains stationary.