Organic Chemistry III

Welcome to Organic Chemistry III!

Welcome! You’ve made it to the final major chapter of Organic Chemistry. In this section, we are going to explore Arenes (like benzene), Amines, and the building blocks of life: Amino Acids and Proteins. We will also look at how chemists design "synthesis routes" to build complex molecules from scratch. Don't worry if it looks like a lot of structures at first—we'll break them down into simple patterns!

18A: Arenes - The Mystery of Benzene

For a long time, chemists were baffled by benzene (\( C_6H_6 \)). It didn’t behave like other "unsaturated" molecules (alkenes). It was much more stable than expected.

The Two Models of Bonding

1. The Kekulé Model: Suggested benzene was a ring of six carbons with alternating single and double bonds.
2. The Delocalised Model: This is the modern view. Each carbon uses three electrons for single bonds. The fourth electron is in a p-orbital. These p-orbitals overlap to form a delocalised ring of electrons (like a "donut" of electricity) above and below the carbon plane.

Evidence for the Delocalised Model

How do we know Kekulé was wrong?
- Bond Lengths: In Kekulé's model, we’d expect long single bonds and short double bonds. In reality, all carbon-carbon bonds in benzene are the same length.
- Enthalpy Change of Hydrogenation: When we add hydrogen to a real benzene ring, it releases less energy than expected compared to a theoretical "Kekulé" ring. This means real benzene is more stable by about \( 152\text{ kJ mol}^{-1} \). This is called resonance stability.
- Resistance to Bromination: Benzene does not decolourise bromine water at room temperature. It won't do "addition" reactions because that would destroy the stable delocalised ring.

Reactions of Benzene

Because the electron ring is so stable, benzene prefers Electrophilic Substitution. An atom or group replaces a hydrogen atom, but the ring stays intact.

- Nitration: React benzene with a mixture of concentrated nitric acid (\( HNO_3 \)) and sulfuric acid (\( H_2SO_4 \)) at \( 50^\circ C \). The sulfuric acid acts as a catalyst to create the electrophile \( NO_2^+ \).
- Bromination: Requires a "halogen carrier" catalyst like \( AlBr_3 \) or \( FeBr_3 \) to create the \( Br^+ \) electrophile.
- Friedel-Crafts Alkylation/Acylation: Using \( AlCl_3 \) as a catalyst, we can add alkyl groups (like \( -CH_3 \)) or acyl groups (like \( -COCH_3 \)) to the ring. This is vital for building larger carbon skeletons.

Phenol: The Reactive Cousin

Phenol is a benzene ring with an \( -OH \) group. It is more reactive than benzene because a lone pair of electrons from the oxygen atom delocalises into the benzene ring. This increases the electron density, making it more attractive to electrophiles.
Example: Phenol reacts instantly with bromine water, forming a white precipitate, without needing a catalyst!

Quick Review: Benzene is a stable, flat hexagon with delocalised electrons. It undergoes substitution, not addition, to keep that stability.

18B: Amines, Amides, and Amino Acids

This section is all about nitrogen-containing compounds. Think of them as derivatives of ammonia (\( NH_3 \)).

Amines: The Organic Bases

Amines have the functional group \( -NH_2 \). They are basic because the nitrogen has a lone pair of electrons that can accept a proton (\( H^+ \)).

Basicity Ranking:
1. Aliphatic Amines (e.g., Ethylamine): Most basic. The alkyl groups "push" electrons toward the nitrogen, making the lone pair more available.
2. Ammonia: The middle ground.
3. Aromatic Amines (e.g., Phenylamine): Least basic. The nitrogen's lone pair gets "tucked away" into the benzene ring's delocalised system.

Making Amines

- From Halogenoalkanes: React with excess ethanolic ammonia (substitution).
- From Nitriles: Reduce using \( LiAlH_4 \) or hydrogen with a nickel catalyst.
- From Nitrobenzene: To make phenylamine, reduce nitrobenzene using tin (\( Sn \)) and concentrated \( HCl \).

Amino Acids and Zwitterions

Amino acids contain both an amine (\( -NH_2 \)) and a carboxylic acid (\( -COOH \)) group.
In the solid state or neutral solution, the acid group loses a proton and the amine group gains one. This creates a "double ion" called a Zwitterion.
Memory Trick: "Zwitter" is German for "hybrid" or "hermaphrodite"—it’s a molecule that is both positive and negative at the same time!

Proteins and Polymerisation

Condensation Polymerisation happens when monomers join and lose a small molecule (like water).
- Polyamides (e.g., Nylon, Kevlar): Formed from dicarboxylic acids and diamines.
- Proteins: Long chains of amino acids joined by peptide bonds (\( -CONH- \)).
- Hydrolysis: We can break these polymers back down into amino acids by heating them with water and a strong acid or alkali.

Key Takeaway: Nitrogen compounds are bases. Amino acids are special because they can act as both an acid and a base, forming Zwitterions.

18C: Organic Synthesis

Synthesis is like a puzzle: how do we get from Molecule A to Molecule B in the fewest steps?

Extending the Carbon Chain: Grignard Reagents

This is a "superhero" reaction in chemistry. We create a Grignard Reagent (\( RMgX \), like \( CH_3MgBr \)) in dry ether.
- React with Carbon Dioxide to make a Carboxylic Acid.
- React with Carbonyls (Aldehydes/Ketones) to make Alcohols.
This is one of the few ways to build a carbon-carbon bond easily!

Practical Techniques: The "How-To" of Organic Chem

Don't worry if these seem tricky; they are just standard "kitchen" techniques for chemists:
- Refluxing: Boiling a liquid so the vapours condense and fall back into the flask. This lets you heat a reaction for a long time without losing your chemicals.
- Recrystallisation: A way to purify solids. Dissolve the impure solid in a minimum amount of hot solvent, let it cool and crystallise, then filter.
- Solvent Extraction: Using a separating funnel to separate a product from a mixture based on its solubility in two different liquids (like oil and water).
- Melting Point Determination: A pure solid has a sharp, specific melting point. If it’s impure, it will melt over a wide range and at a lower temperature.

Common Mistakes to Avoid

- Catalysts: Forgetting the catalyst in benzene reactions (e.g., you must have \( AlCl_3 \) for Friedel-Crafts).
- Conditions: Confusing "reflux" with "distillation." Reflux keeps everything in; distillation takes the product out.
- Basicity: Thinking phenylamine is a strong base. It's actually very weak because the lone pair is "busy" with the ring.

Final Summary

Organic Chemistry III pulls everything together. You’ve learned that benzene is a stable ring that prefers substitution. You’ve seen how nitrogen makes molecules basic and how amino acids build the proteins in your body. Finally, you’ve learned the tools to build and purify these molecules in the lab. You're now thinking like a real synthetic chemist! Keep practicing those reaction mechanisms, and they will become second nature.