Welcome to Organic Nitrogen Chemistry!
Hello future chemists! You are about to dive into one of the most exciting and essential areas of organic chemistry: Organic Nitrogen Compounds. Why are these so important? Because nitrogen is the core element of life itself! It builds our DNA, it forms the crucial structures of proteins, and it powers many modern medicines and dyes. These molecules are everywhere!
Don’t worry if this chapter seems dense at first. We will break down amines, amides, amino acids, and proteins into simple, manageable concepts. Let’s get started!
Key Takeaway from the Introduction:
Nitrogen forms unique functional groups that act as bases (amines) and create strong bonds (amides), making them central to biological chemistry.
1. Amines: The Organic Bases
Amines are organic derivatives of ammonia (\(NH_3\)), where one or more hydrogen atoms have been replaced by alkyl (R) or aryl (Ar) groups.
Classification and Nomenclature
We classify amines based on how many carbon atoms are directly bonded to the nitrogen atom:
- Primary Amine (\(1^\circ\)): The N atom is bonded to one carbon group. (e.g., Methylamine, \(CH_3NH_2\)).
- Secondary Amine (\(2^\circ\)): The N atom is bonded to two carbon groups. (e.g., Dimethylamine, \((CH_3)_2NH\)).
- Tertiary Amine (\(3^\circ\)): The N atom is bonded to three carbon groups. (e.g., Trimethylamine, \((CH_3)_3N\)).
Nomenclature Trick: Name the alkyl groups attached to the nitrogen first, followed by the suffix -amine. If it's a primary amine on a long chain, use amino- as a prefix (e.g., 2-aminopropane).
Basicity of Amines (The Lone Pair)
Amines are bases because the nitrogen atom possesses a lone pair of electrons.
Definition of Basicity: A base is an electron-pair donor (Lewis base) or a proton (\(H^+\)) acceptor (Brønsted-Lowry base).
When an amine reacts with water, it accepts a proton, forming an alkylammonium ion and a hydroxide ion:
\[ R-NH_2 + H_2O \rightleftharpoons R-NH_3^+ + OH^- \]
Why are amines stronger bases than ammonia? (Aliphatic Amines)
In aliphatic amines (like methylamine), the alkyl groups (R) are electron-releasing. This phenomenon is called the positive inductive effect.
- The alkyl groups push electron density towards the N atom.
- This concentrates the negative charge on the N atom, making the lone pair more available to accept a proton.
Strength Order: Secondary (\(2^\circ\)) > Primary (\(1^\circ\)) > Tertiary (\(3^\circ\)) ≈ Ammonia (in aqueous solution). Note: Tertiary amines are often slightly weaker than \(1^\circ\) or \(2^\circ\) due to steric hindrance (the bulky R groups make it hard for the proton to reach the nitrogen).
Why are aromatic amines weak bases? (Aryl Amines)
In aromatic amines (like Phenylamine, \(\text{C}_6\text{H}_5\text{NH}_2\)), the lone pair of electrons on the nitrogen is delocalised into the benzene ring.
- The lone pair is less available to accept a proton.
- Therefore, aromatic amines are much weaker bases than ammonia or aliphatic amines.
Synthesis of Amines
There are two key methods for synthesizing amines that you must know:
1. Reduction of Nitriles (For Aliphatic Amines)
Nitriles (\(R-C\equiv N\)) can be reduced to primary amines using a powerful reducing agent, usually Lithium Aluminium Hydride (\(LiAlH_4\)) in dry ether, followed by reaction with dilute acid. Alternatively, catalytic hydrogenation (H₂ gas over a nickel catalyst) can be used, especially in industry.
\[ R-C\equiv N + 4[H] \xrightarrow{LiAlH_4} R-CH_2NH_2 \]
Step-by-Step Focus: This reaction increases the carbon chain length by one C atom.
2. Reduction of Nitroarenes (For Aromatic Amines)
This is the standard route to make phenylamine, a key intermediate in dye manufacturing.
Process:
- React the nitroarene (e.g., nitrobenzene) with Tin (Sn) and concentrated Hydrochloric Acid (HCl) under reflux. This reduces the nitro group (\(NO_2\)) to an ammonium salt (\(NH_3^+Cl^-\)).
- Add excess Sodium Hydroxide (NaOH) to the mixture to neutralise the salt and release the free amine.
\[ C_6H_5NO_2 \xrightarrow{Sn, conc. HCl} C_6H_5NH_3^+Cl^- \xrightarrow{NaOH} C_6H_5NH_2 \]
Common Mistake Alert: Students often forget the final neutralisation step with NaOH. You MUST add a strong base to liberate the amine from its salt!
Reactions of Amines: Salt Formation
Since amines are bases, they react with acids to form salts (alkylammonium salts). These salts are ionic and usually solid and odourless, unlike the volatile, fishy-smelling amines themselves.
\[ R-NH_2 + HCl \rightarrow R-NH_3^+Cl^- \text{ (Alkylammonium chloride)} \]
Did you know? Many drugs (like antihistamines) are stored and sold as their ammonium salts because they are more stable and easier to handle than the free amine.
Quick Review: Amines
Amines are classified by the number of carbons attached to N. They are bases due to the lone pair. Basicity is enhanced by alkyl groups (inductive effect) but weakened by benzene rings (delocalisation).
2. Amides: The Neutral Link
Amides are formed when the hydroxyl group (-OH) of a carboxylic acid is replaced by an amino group (-\(NH_2\)) or a substituted amino group (\(-NHR\) or \(-NR_2\)). The functional group is R-CONH-R'.
The simplest amide is ethanamide (\(CH_3CONH_2\)).
Structure and Properties
Unlike amines, simple amides are neutral. Why?
The carbonyl group (\(C=O\)) is highly electronegative and strongly pulls electron density away from the nitrogen atom. This delocalisation of the nitrogen's lone pair into the C=O group makes the lone pair completely unavailable to accept a proton.
Analogy: Imagine the lone pair is tied up helping the C=O group stabilize itself; it can’t escape to bond with an \(H^+\).
Synthesis of Amides (Acylation)
Amides are formed by reacting a carboxylic acid derivative with ammonia or an amine. The most common laboratory route uses an acyl chloride (acid chloride) or acid anhydride because these are much more reactive than carboxylic acids.
Reaction Example (using acyl chloride):
\[ RCOCl + NH_3 \rightarrow RCONH_2 + HCl \]
This reaction is a nucleophilic addition-elimination reaction. It occurs readily at room temperature, often with violent reaction if the acyl chloride is small.
Hydrolysis of Amides
Amides can be broken down (hydrolysed) back into their starting components using heat and either a strong acid or a strong base.
1. Acid Hydrolysis (Heating with dilute acid, e.g., HCl)
The products are the carboxylic acid and an ammonium salt.
\[ RCONH_2 + H_2O + HCl \xrightarrow{Heat} RCOOH + NH_4^+Cl^- \]
2. Base Hydrolysis (Heating with dilute alkali, e.g., NaOH)
The products are the salt of the carboxylic acid (a carboxylate salt) and ammonia (or the free amine).
\[ RCONH_2 + NaOH \xrightarrow{Heat} RCOO^-Na^+ + NH_3 \]
Memory Aid: If you hydrolyse with Acid, you get the Acid (carboxylic acid). If you hydrolyse with Base, you get the Salt (carboxylate salt).
3. Amino Acids: The Amphoteric Zwitterions
Amino acids are the fundamental building blocks of proteins. They are unique because they contain two different functional groups attached to the same central carbon atom (the alpha-carbon):
- An Amine group (\(-NH_2\)) – acts as a base.
- A Carboxyl group (\(-COOH\)) – acts as an acid.
The general formula is \(H_2N-CH(R)-COOH\), where R is the side chain.
Stereoisomerism in Amino Acids
The alpha-carbon in an amino acid is usually a chiral centre (or asymmetric carbon). A chiral centre is a carbon atom bonded to four different groups.
Exception: Glycine (\(R=H\)) is the only amino acid that is not chiral because its alpha-carbon is bonded to two identical hydrogen atoms.
Because most amino acids are chiral, they exist as non-superimposable mirror images of each other, called enantiomers (optical isomers).
The Zwitterion Structure
Amino acids exist predominantly as zwitterions (from the German word for "hybrid ion") at their isoelectric point (a neutral pH).
- In solution, the acidic carboxyl group (\(-COOH\)) loses a proton (\(H^+\)).
- This proton is immediately accepted by the basic amino group (\(-NH_2\)).
- The resulting molecule has both a positive charge (\(-NH_3^+\)) and a negative charge (\(-COO^-\)), making it a dipolar ion, but overall electrically neutral.
\[ H_2N-CH(R)-COOH \rightleftharpoons ^+H_3N-CH(R)-COO^- \text{ (Zwitterion)} \]
Amphoteric Behaviour (Reactions)
Since amino acids contain both acidic and basic groups, they are amphoteric – they can react with both acids and bases.
1. Reaction with Acid (Low pH)
In acidic solution, the basic group (the negative carboxylate ion, \(-COO^-\)) accepts a proton. The amino acid exists as a positively charged ion:
\[ ^+H_3N-CH(R)-COO^- + HCl \rightarrow ^+H_3N-CH(R)-COOH + Cl^- \]
2. Reaction with Base (High pH)
In basic solution, the acidic group (the positive ammonium ion, \(-NH_3^+\)) donates a proton. The amino acid exists as a negatively charged ion:
\[ ^+H_3N-CH(R)-COO^- + NaOH \rightarrow H_2N-CH(R)-COO^-Na^+ + H_2O \]
Practical Use: This amphoteric nature allows us to separate and identify amino acids using techniques like electrophoresis, as their charge changes depending on the pH of the solution.
4. Peptides and Proteins: The Polymers of Life
Proteins are biological polymers formed by joining large numbers of amino acids together.
Peptide Bond Formation (Condensation)
When two amino acids react, they link together through a condensation reaction, losing a molecule of water. This forms an amide link, which in biological systems is called a peptide bond.
- The carboxyl group of one amino acid reacts with the amine group of a second amino acid.
- Water (\(H_2O\)) is eliminated.
- The resulting molecule is a dipeptide.
\[ \text{Amino Acid 1} + \text{Amino Acid 2} \xrightarrow{\text{Condensation}} \text{Dipeptide} + H_2O \]
Structure of the Peptide Bond: The link is always -CO-NH-.
Many amino acids linking together form a polypeptide. A polypeptide with a very high molecular mass and a complex structure is called a protein.
Hydrolysis of Proteins
The peptide bond is highly stable, but it can be broken down (hydrolysed) by heating with concentrated acid or by using specific enzymes (proteases).
Hydrolysis is the reverse of condensation – a molecule of water is added back across the peptide bond, separating the chain back into its constituent amino acids.
\[ \text{Polypeptide} + nH_2O \xrightarrow{\text{Hot conc. Acid/Enzyme}} \text{Amino Acids} \]
Did you know? Digestion is essentially the enzyme-catalysed hydrolysis of the proteins we eat, breaking them down into amino acids that our body can absorb and reuse to build new proteins.
Key Takeaway: Polymers
Amino acids condense to form polymers (polypeptides/proteins) linked by peptide bonds (-CO-NH-). Hydrolysis breaks these bonds back into amino acids.
You have successfully covered the core concepts of Organic Nitrogen Chemistry! Remember to practice drawing the structures and balancing the hydrolysis equations. You’ve got this!