Ch 1 · Organic synthesis · AS & A Level Chemistry 9701

Topic 1 of 1 in Organic synthesis — AS & A Level Chemistry 9701 — 58 lessons.

Introduction

A2 organic synthesis extends the AS skill of linking single-step reactions into routes, now drawing on the full range of A2 functional groups — arenes, acyl chlorides, amides and amines — and requiring routes that change the length of a carbon chain or create a new stereocentre.

Key ideas — Identifying functional groups in a polyfunctional molecule

A2 molecules often combine several functional groups from across the syllabus: 4-aminobenzoic acid, for example, contains both an aromatic amine, -NH_2 attached to a benzene ring, and a carboxylic acid, -COOH, each reacting independently. Scanning systematically for mathrmC=C, aromatic rings, -OH, -X, mathrmC=O, -COOH, -COCl (acyl chloride), -CONH_2 (amide), -NH_2 and -mathrmC≡N identifies every group present, including groups attached directly to an aromatic ring, which often react differently from the same group on an aliphatic chain.

🧑‍🏫 Teacher's explanation

Think of a polyfunctional molecule like a Swiss Army knife. A standard tool might only have one blade (one functional group), but a complex tool has a screwdriver, a knife, and scissors. If you want to know how the tool behaves, you don't just look at the whole object; you identify each individual tool first. In organic chemistry, the 'tools' are the functional groups.

📖 Definitions

🔍 Worked example — Easy

Identify all functional groups present in the molecule C_6H_5NH_2 (aniline).

🔍 Worked example — Standard

Identify the functional groups in 3-hydroxybutanoic acid (CH_3CH(OH)CH_2COOH).

🔍 Worked example — Exam-style

A molecule has the formula CH_3COCl. Identify the functional group and predict its reactivity toward water.

⚠️ Common errors

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🎯 Exam question

Key ideas — Predicting properties and reactions from functional groups

Each functional group reacts according to its own chemistry regardless of the rest of the molecule: an acyl chloride, -COCl, reacts rapidly and exothermically with water, alcohols and amines without a catalyst, forming a carboxylic acid, an ester or an amide respectively; a primary aromatic amine such as phenylamine is a much weaker base than an aliphatic amine, since the nitrogen lone pair is delocalised into the ring, but reacts readily with nitrous acid at low temperature to form a diazonium salt. Predicting behaviour correctly requires recognising whether a group is aliphatic or attached to an aromatic ring, since the ring can both activate and deactivate different reactions.

🧑‍🏫 Teacher's explanation

Think of an organic molecule like a complex machine. The carbon skeleton is the frame, but the functional groups are the 'active components' like buttons, levers, or engines. Even if the machine is huge and complex, if you press the 'on' button (the functional group), that specific part will react according to its own design, regardless of what the rest of the machine looks like.

📖 Definitions

🔍 Worked example — Easy

Predict the products of the reaction between ethanoyl chloride and methanol under standard conditions.

🔍 Worked example — Standard

Compare the basicity of $ ext{CH}_3 ext{NH}_2$ and $ ext{C}_6 ext{H}_5 ext{NH}_2$. Which is a stronger base and why?

🔍 Worked example — Exam-style

A synthetic route involves reacting $ ext{C}_2 ext{H}_5 ext{OH}$ with $ ext{PCl}_5$ to form $ ext{C}_2 ext{H}_5 ext{Cl}$, followed by reaction with $ ext{KCN}$ to form $ ext{C}_2 ext{H}_5 ext{CN}$. Calculate the total number of carbon atoms in the final product.

⚠️ Common errors

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🎯 Exam question

(a) Suggest a two-step synthetic route involving an acyl chloride intermediate. (b) Write the balanced equation for the reaction between propanoyl chloride and ammonia ($ ext{NH}_3$). [3 marks]

Key ideas — Extending chain length in a route

Some A2 target molecules need a longer carbon chain than the given starting material provides. The standard route adds one carbon: a halogenoalkane is refluxed with potassium cyanide in ethanol to substitute -X with -mathrmC≡N, giving a nitrile with one extra carbon atom, which can then be hydrolysed under reflux with dilute acid to a carboxylic acid, or reduced (for example with LiAlH_4) to a primary amine with one extra carbon compared with the original halogenoalkane.

🧑‍🏫 Teacher's explanation

Think of building a Lego model. Sometimes you have a base piece, but the model you want to build is longer. To make it longer, you need a 'connector' piece that snaps onto the end and adds a new unit. In organic chemistry, we use specific reagents to 'snap' a new carbon atom onto an existing chain.

📖 Definitions

🔍 Worked example — Easy

Starting with bromoethane, C_2H_5Br, show the chemical equation for the first step to produce a nitrile with one additional carbon atom.

🔍 Worked example — Standard

A student reacts propanenitrile, CH_3CH_2CN, with dilute H_2SO_4 under reflux. Write the formula of the organic product formed.

🔍 Worked example — Exam-style

Calculate the percentage mass increase when 1 mole of chloroethane, C_2H_5Cl, is converted to propanenitrile, C_3H_5N, via the cyanide route. (Use A_r: C=12, H=1, Cl=35.5, N=14)

⚠️ Common errors

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🎯 Exam question

Key ideas — Introducing a stereocentre in a route

A route can introduce a new chiral centre where none existed, most commonly by nucleophilic addition of hydrogen cyanide to a carbonyl compound: the planar mathrmC=O carbon of an aldehyde or an unsymmetrical ketone becomes a tetrahedral carbon bonded to four different groups once -OH and -CN have added across the double bond, and because the nucleophile can attack either face of the planar carbonyl with equal probability, the product is a racemic mixture of both enantiomers.

🧑‍🏫 Teacher's explanation

Imagine you are standing in front of a flat, two-dimensional table (the planar carbonyl group). You are holding a ball (the cyanide ion) and you want to throw it at the table. Because the table is flat and symmetrical, you are just as likely to hit it from the top as you are from the bottom. Once the ball hits, the table 'pops' into a 3D shape, and the point where it hit is now a new corner of the structure.

📖 Definitions

🔍 Worked example — Easy

Identify the number of stereocentres in propanal, CH_3CH_2CHO, and predict the nature of the product when reacted with HCN.

🔍 Worked example — Standard

Predict the product of the reaction between propanone (CH_3COCH_3) and HCN, including state symbols.

🔍 Worked example — Exam-style

A chemist reacts ethanal (CH_3CHO) with HCN followed by hydrolysis using dilute H_2SO_4. Draw the final organic product and state if it is chiral.

⚠️ Common errors

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🎯 Exam question

Key ideas — Analysing reaction type, reagents and by-products

Each step of a route is classified and justified by reaction type (nucleophilic substitution, addition, oxidation, reduction, condensation or electrophilic substitution), the specific reagent and condition needed, and the by-product formed, since separate marks are awarded for each: forming an amide from an acyl chloride and an amine, for instance, is a condensation reaction using the amine (often in excess) at room temperature, producing hydrogen chloride (or its salt with excess amine) as the by-product.

🧑‍🏫 Teacher's explanation

Think of organic synthesis like a complex LEGO construction project. You have a set of starting blocks (reactants), and you want to build a specific model (the product). To get there, you can't just smash them together; you need specific tools (reagents) and sometimes heat or pressure (conditions).

📖 Definitions

🔍 Worked example — Easy

Identify the reaction type and the by-product for the reaction: CH_3COCl + NH_3 arrow CH_3CONH_2 + ?

🔍 Worked example — Standard

A student reacts propanoic acid with methanol in the presence of a concentrated H_2SO_4 catalyst to produce methyl propanoate. State the reaction type and the by-product.

🔍 Worked example — Exam-style

Analyze the following step in a synthesis: C_2H_5Br + NaOH (aq) arrow C_2H_5OH + NaBr. State the reaction type and the reagent/condition required to favor this specific product over an alkene.

⚠️ Common errors

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🎯 Exam question

(a) Suggest a reagent that would be used to convert ethanoic acid into ethanoyl chloride. (b) Describe the reaction type and the by-product formed when ethanoyl chloride reacts with methylamine (CH_3NH_2). [3] [3 marks]

Worked example

Question. Devise a synthetic route to convert bromoethane into 2-hydroxypropanenitrile, CH_3CH(OH)CN, in three steps, stating reagents, conditions, reaction type and any by-product for each step, and identify which step introduces a new stereocentre. [8]

All chapters in Organic synthesis

Organic synthesis