Chemistry (9701) | Nitrogen compounds

✨ Comprehensive Study Notes: Nitrogen Compounds (9701 AS & A Level Chemistry)

Welcome to the exciting world of Nitrogen Compounds! This chapter links several key areas of organic chemistry, introducing functional groups like amines, nitriles, amides, and the fundamental structures of life—amino acids.
Don't worry if the reaction sequences seem long; we will break down the preparations and reactions into simple, logical steps. Understanding the role of the nitrogen lone pair is key to mastering this topic!

Section 1: Amines (R-$\text{NH}_2$)

1.1 Understanding Amines and Classification

Amines are organic derivatives of ammonia ($\text{NH}_3$) where one or more hydrogen atoms have been replaced by alkyl (R) or aryl groups. The crucial feature is the lone pair of electrons on the nitrogen atom, which dictates most of the amine's chemistry.

Classification (Quick Review):
(Although formal classification testing is limited at AS, understanding these terms is vital for A-Level reactions):

• Primary Amine (1°): One alkyl group attached to N. E.g., Ethylamine ($\text{CH}_3\text{CH}_2\text{NH}_2$).
• Secondary Amine (2°): Two alkyl groups attached to N.
• Tertiary Amine (3°): Three alkyl groups attached to N.

1.2 Preparation of Primary and Secondary Amines

Method 1: From Halogenoalkanes (Nucleophilic Substitution) (34.1(a))

This reaction uses ammonia or an amine as a nucleophile to replace the halogen (X) atom on a halogenoalkane.

Reaction 1: Making a Primary Amine (using $\text{NH}_3$)

• Reagents: Halogenoalkane (e.g., bromoethane) and excess concentrated ammonia ($\text{NH}_3$).
• Conditions: In ethanol (ethanolic solution) and heated under pressure (in a sealed tube).
• Issue to know: Using halogenoalkane and ammonia often leads to a mixture of products (primary, secondary, and tertiary amines, and the quaternary ammonium salt) because the resulting primary amine is itself a strong nucleophile and can react further. To maximize the yield of the primary amine, we must use a large excess of ammonia.

Reaction 2: Making a Secondary Amine (using a 1° amine)

• Reagents: Halogenoalkane and a primary amine (e.g., ethylamine).
• Conditions: In ethanol, heated under pressure.
• This reaction produces a secondary amine and can proceed further to tertiary amines and quaternary salts.

Method 2: Reduction of Nitriles or Amides (34.1(c), 34.1(d))

Reduction converts the carbon-nitrogen bonds into a $\text{C-N}$ single bond, adding hydrogen atoms. This is a great way to ensure you only get a primary amine.

Reduction of Nitriles ($\text{R-C} \equiv \text{N}$):

• Reagents: Strong reducing agent, usually Lithium aluminium hydride ($\text{LiAlH}_4$) in dry ether, followed by aqueous acid. OR Hydrogen ($\text{H}_2$) with a Nickel ($\text{Ni}$) catalyst.
• Product: Primary amine. The chain length increases by one carbon atom compared to the starting halogenoalkane (if nitrile was made from a halogenoalkane).
• Equation (using $\text{LiAlH}_4$ - simplified):
  $$ \text{R-C} \equiv \text{N} + 4[\text{H}] \xrightarrow{\text{LiAlH}_4} \text{RCH}_2\text{NH}_2 $$

Reduction of Amides ($\text{RCONH}_2$):

• Reagents: Lithium aluminium hydride ($\text{LiAlH}_4$) in dry ether, followed by aqueous acid.
• Product: Primary amine.
• Equation (simplified):
  $$ \text{RCONH}_2 + 4[\text{H}] \xrightarrow{\text{LiAlH}_4} \text{RCH}_2\text{NH}_2 + \text{H}_2\text{O} $$

1.3 Basicity of Amines

All amines are bases because the nitrogen atom has a lone pair of electrons that can accept a proton ($\text{H}^+$). This ability is explained by the Brønsted-Lowry theory of acids and bases (34.1.3).

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

The basicity depends on how available that lone pair is to bind to $\text{H}^+$.

Basicity Trend Comparison (34.2.3)

The trend in basicity for common aqueous solutions is:
Ethylamine (strongest) > Ammonia > Phenylamine (weakest) > Amides

1. Ethylamine ($\text{CH}_3\text{CH}_2\text{NH}_2$):

• The alkyl group ($\text{CH}_3\text{CH}_2$-) is an electron-donating group.
• This pushes electron density onto the nitrogen atom, making the lone pair more localized, more available, and therefore a much stronger base than ammonia.

2. Ammonia ($\text{NH}_3$):

• Ammonia acts as the baseline (medium base). It has no donating or withdrawing groups affecting the lone pair.

3. Phenylamine ($\text{C}_6\text{H}_5\text{NH}_2$):

• The phenyl group ($\text{C}_6\text{H}_5$-) is an electron-withdrawing group.
• The lone pair on the nitrogen partially delocalizes into the $\pi$-system of the benzene ring.
• This makes the lone pair less available to accept a proton, making phenylamine a much weaker base than ammonia.

4. Amides ($\text{RCONH}_2$):

• Amides are even weaker bases than phenylamine (34.3.3).
• The strong electron-withdrawing effect of the carbonyl group ($\text{C=O}$) causes severe delocalization of the nitrogen lone pair, making it almost impossible for the nitrogen to accept a proton.

Section 2: Nitriles ($\text{R-C} \equiv \text{N}$) and Hydroxynitriles

2.1 Preparation of Nitriles (19.2)

Nitriles are synthesized through a nucleophilic substitution reaction involving a halogenoalkane.

• Reagents: Halogenoalkane (e.g., bromoethane) and Potassium cyanide ($\text{KCN}$).
• Conditions: $\text{KCN}$ must be dissolved in ethanol (ethanolic solution) and heated gently.
• Function: The cyanide ion ($\text{CN}^-$) acts as a nucleophile, replacing the halogen. This reaction is highly useful because it increases the carbon chain length by one C atom.
• Equation:
  $$ \text{R-X} + \text{KCN} \xrightarrow{\text{ethanol/heat}} \text{R-C} \equiv \text{N} + \text{KX} $$

2.2 Preparation of Hydroxynitriles (19.2)

Hydroxynitriles are produced when aldehydes or ketones undergo a nucleophilic addition reaction across the carbonyl ($\text{C=O}$) double bond.

• Reagents: Aldehyde or Ketone (e.g., ethanal or propanone) and Hydrogen cyanide ($\text{HCN}$).
• Conditions: $\text{KCN}$ must be present as a catalyst, and the mixture is heated. ($\text{KCN}$ acts as the source of the strong nucleophile $\text{CN}^-$).

Mechanism: Nucleophilic Addition (17.1.3)

1. The nucleophilic cyanide ion ($\text{CN}^-$) attacks the partially positive ($\delta^+$) carbon atom in the carbonyl group. The $\pi$-bond breaks.
2. The oxygen atom gains a pair of electrons, forming an alkoxide ion ($\text{C-O}^-$).
3. The alkoxide ion rapidly takes a proton ($\text{H}^+$) from the surrounding solution ($\text{H}_2\text{O}$ or $\text{HCN}$) to form the hydroxynitrile.

2.3 Reactions: Hydrolysis of Nitriles and Hydroxynitriles (19.2, 18.1)

Nitriles can be converted into carboxylic acids by hydrolysis.

Hydrolysis (Acidic conditions):

• Reagents: Dilute acid (e.g., dilute $\text{HCl}$ or $\text{H}_2\text{SO}_4$).
• Conditions: Heating (Reflux).
• Product: Carboxylic acid ($\text{RCOOH}$).

Hydrolysis (Alkaline conditions):

• Reagents: Dilute alkali (e.g., dilute $\text{NaOH}$), followed by acidification.
• Conditions: Heating (Reflux).
• Product: A carboxylate salt ($\text{RCOO}^-\text{Na}^+$), which is then converted to the carboxylic acid ($\text{RCOOH}$) upon acidification.

Section 3: Aromatic Nitrogen Compounds (Phenylamine)

3.1 Preparation of Phenylamine (Aniline) (34.2.1)

Phenylamine is the simplest aromatic amine. It is prepared via a two-step reduction process starting from benzene.

Step 1: Nitration of Benzene

• Benzene is reacted with a nitrating mixture (concentrated $\text{HNO}_3$ and concentrated $\text{H}_2\text{SO}_4$) at $50-60^\circ\text{C}$ to form nitrobenzene ($\text{C}_6\text{H}_5\text{NO}_2$). (This is electrophilic substitution.)

Step 2: Reduction of Nitrobenzene

• Reagents: Hot tin ($\text{Sn}$) and concentrated hydrochloric acid ($\text{HCl}$). (This combination generates the necessary nascent hydrogen, $[\text{H}]$).
• Conditions: Heating (Reflux).
• Intermediate Product: The nitro group ($\text{NO}_2$) is reduced to an amine group ($\text{NH}_2$). Initially, the amine forms a salt ($\text{C}_6\text{H}_5\text{NH}_3^+ \text{Cl}^-$) with the excess acid.
• Final Step: Aqueous sodium hydroxide ($\text{NaOH}(\text{aq})$) is added to liberate the free amine base, phenylamine.

3.2 Reactions of Phenylamine

A. Reaction with Bromine Water (34.2.2(a))

The lone pair on the nitrogen atom in phenylamine is only partially delocalized into the ring (see section 1.3). However, it is still strongly activating, meaning it directs incoming electrophiles to the 2, 4, and 6 positions and makes the ring very reactive.

• Reagent: Aqueous bromine ($\text{Br}_2(\text{aq})$).
• Conditions: Room temperature.
• Observation: Decolourisation of the orange/brown bromine water and the formation of a white precipitate (2,4,6-tribromophenylamine).
• This high reactivity means a catalyst is not needed, unlike the bromination of plain benzene.

B. Diazotisation and Azo Dye Formation (Coupling) (34.2.2(b), 34.2.4)

Diazotisation converts the primary aromatic amine into a highly reactive intermediate called a diazonium salt ($\text{Ar-N}_2^+$). This must be kept cold.

1. Diazotisation:

• Reagents: Phenylamine, nitrous acid ($\text{HNO}_2$) or sodium nitrite ($\text{NaNO}_2$) and dilute acid (e.g., $\text{HCl}$).
• Conditions: Temperature below $10^\circ\text{C}$ (usually $0-5^\circ\text{C}$).
• Product: Benzenediazonium chloride ($\text{C}_6\text{H}_5\text{N}_2^+\text{Cl}^-$).

2. Coupling:

• The diazonium salt is mixed with phenol ($\text{C}_6\text{H}_5\text{OH}$) dissolved in aqueous sodium hydroxide ($\text{NaOH}(\text{aq})$).
• The reaction is a substitution that forms a bright, highly coloured compound containing the azo group ($\text{-N=N-}$).
• Azo compounds are widely used as dyes due to their extensive delocalized system allowing them to absorb and reflect visible light.

Section 4: Amides ($\text{RCONH}_2$)

4.1 Preparation of Amides (Acylation) (34.3.1)

Amides are formed via a condensation reaction between an acyl chloride and a nitrogen nucleophile ($\text{NH}_3$ or an amine).

Amide Synthesis (General Reaction):

• Reagents: Acyl chloride (e.g., ethanoyl chloride) and either ammonia ($\text{NH}_3$) or a primary/secondary amine.
• Conditions: Room temperature. (Acyl chlorides are highly reactive!).
• Products: An amide + $\text{HCl}$.

Example 1: Using Ammonia (to make a primary amide)
$$ \text{RCOCl} + 2\text{NH}_3 \rightarrow \text{RCONH}_2 + \text{NH}_4\text{Cl} $$

Example 2: Using a Primary Amine (to make a secondary amide)
$$ \text{RCOCl} + 2\text{R}'\text{NH}_2 \rightarrow \text{RCONHR}' + \text{R}'\text{NH}_3^+\text{Cl}^- $$

4.2 Reactions of Amides (34.3.2)

Amides are relatively unreactive, requiring harsh conditions (strong acid/base or powerful reducing agents) to react.

1. Hydrolysis: Reverting to carboxylic acid

• Acidic Hydrolysis: Heating with aqueous acid (e.g., dilute $\text{HCl}$). Produces a carboxylic acid and the ammonium ion (or amine salt).
• Alkaline Hydrolysis: Heating with aqueous alkali (e.g., $\text{NaOH}$). Produces a carboxylate salt and ammonia (or the free amine).

2. Reduction: Forming an amine

• Reagents: Powerful reducing agent Lithium aluminium hydride ($\text{LiAlH}_4$).
• Conditions: In dry ether, followed by acid/water workup.
• Product: Primary amine. This reaction reduces the carbonyl group ($\text{C=O}$) to a methylene group ($\text{CH}_2$).
• Equation (simplified):
  $$ \text{RCONH}_2 + 4[\text{H}] \xrightarrow{\text{LiAlH}_4} \text{RCH}_2\text{NH}_2 + \text{H}_2\text{O} $$

Section 5: Amino Acids (34.4)

5.1 Structure and Zwitterions

Amino acids are bifunctional molecules, meaning they contain two functional groups: an amine group ($\text{-NH}_2$) and a carboxyl group ($\text{-COOH}$).

Acid/Base Properties and Zwitterions (34.4.1)

In aqueous solution, amino acids exist predominantly as zwitterions (German for "hybrid ions").

• The acidic carboxyl group ($\text{-COOH}$) loses a proton ($\text{H}^+$).
• The basic amino group ($\text{-NH}_2$) accepts that proton.

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

Isoelectric Point ($\text{pI}$) (34.4.1)

The isoelectric point ($\text{pI}$) is the specific $\text{pH}$ at which the amino acid exists mostly as the neutral zwitterion, and therefore has zero net charge.

• At $\text{pH} = \text{pI}$, the amino acid will not move in an electric field.
• At $\text{pH} < \text{pI}$ (acidic conditions), the molecule gains a proton and is positively charged ($\text{H}_3\text{N}^+\text{CH(R)COOH}$).
• At $\text{pH} > \text{pI}$ (alkaline conditions), the molecule loses a proton and is negatively charged ($\text{H}_2\text{NCH(R)COO}^-$).

5.2 Peptide Bonds (34.4.2)

Amino acids link together through a condensation reaction between the carboxyl group of one amino acid and the amino group of another, forming an amide bond, known in biochemistry as a peptide bond ($\text{-CONH-}$).

$$ \text{Amino Acid}_1 \text{ (-COOH)} + \text{Amino Acid}_2 \text{ (-NH}_2\text{)} \rightarrow \text{Dipeptide} + \text{H}_2\text{O} $$

Two amino acids form a dipeptide. Three form a tripeptide. Many form a polypeptide (protein).

5.3 Electrophoresis (34.4.3)

Electrophoresis is a technique used to separate a mixture of amino acids or peptides based on their charge.

• Amino acids are placed on an absorbent paper or gel soaked in a buffer solution of a known $\text{pH}$.
• An electric field is applied.
• The direction and speed of movement depend entirely on the net charge of the molecule at that specific $\text{pH}$.
• Prediction: If the $\text{pH}$ of the buffer is...
  • ...equal to the $\text{pI}$: the amino acid is neutral (zwitterion) and does not move.
  • ...lower than the $\text{pI}$: the amino acid is positively charged and moves towards the negative electrode (cathode).
  • ...higher than the $\text{pI}$: the amino acid is negatively charged and moves towards the positive electrode (anode).