Organic synthesis

In a nutshell

Organic synthesis is about making a target compound on purpose: choosing the reactions, carrying them out with the right apparatus, and purifying the product.

This subtopic pulls together every reaction in Module 4. You need the practical techniques (reflux, distillation, separating funnel, drying, redistillation), the skill of spotting functional groups in a bigger molecule, and the skill of planning two-stage synthetic routes.

Assumed knowledge: Alkenes, Alcohols, Haloalkanes, Amount of substance (percentage yield).

Core content

Practical skills: Quickfit apparatus for heating under reflux

Quickfit apparatus is glassware with ground-glass joints that fit together tightly without corks or bungs. The same flask, condenser and still head can be rebuilt into different set-ups.

Heating under reflux means heating a reaction mixture with a vertical condenser fitted to the flask. Vapours rise, condense and drip back into the flask, so no volatile reactant or product is lost.

You reflux when a reaction is slow and needs prolonged heating, for example:

• hydrolysis of a haloalkane with NaOH(aq)
• oxidation of a primary alcohol all the way to a carboxylic acid
• making a haloalkane from an alcohol with NaBr/H₂SO₄

The details examiners check on a reflux diagram:

• The condenser is vertical and open at the top. A sealed system would build up pressure as it is heated.
• Cooling water goes in at the bottom and out at the top, so the jacket stays full of water.
• Anti-bumping granules go in the flask so the liquid boils smoothly, without large violent bubbles.
• An electric heater (heating mantle or water bath) is used rather than a naked flame, because most organic liquids are flammable.
• No lines are drawn across the joints between flask and condenser, since a line looks like a seal.

Practical skills: Quickfit apparatus for distillation

Distillation separates a liquid from a mixture by boiling it off, condensing the vapour and collecting it in a separate flask. It works because the components have different boiling points.

The details that earn the marks:

• The thermometer bulb is level with the side-arm of the still head, so it reads the temperature of the vapour entering the condenser, not of the boiling liquid.
• The condenser slopes down towards the collecting flask, with water in at the lower end.
• The collecting end is not sealed to the condenser.
• You collect the liquid that distils over a narrow range close to the product's boiling point.

Practical skills: preparing and purifying an organic liquid

A crude organic liquid straight from a reaction is contaminated with water, acid, unreacted starting material and by-products. Purification removes each one in turn.

1. Separating funnel. Shake the crude product with an aqueous solution, let the two immiscible layers settle, then run off the layers through the tap and keep the organic layer.
2. Washing. Shaking with sodium hydrogencarbonate solution neutralises acid impurities. It produces CO₂, so invert the funnel and open the tap regularly to release the pressure.
3. Drying. Run the organic layer into a dry conical flask and add an anhydrous salt such as anhydrous MgSO₄ or anhydrous CaCl₂. It absorbs the water left dissolved in the organic liquid. The liquid turns from cloudy to clear when it is dry.
4. Decant (pour off) or filter the dried liquid away from the solid drying agent.
5. Redistillation. Distil the dried liquid again and collect only the fraction boiling close to the product's boiling point. This separates the product from other organic impurities, such as unreacted starting material, which have different boiling points.

Which layer is which? The denser liquid sinks to the bottom. Many organic liquids are less dense than water and float on top, but not all: haloalkanes containing bromine or iodine are often denser than water, so they form the lower layer. Check the density, or add a few drops of water and see which layer grows.

Still don't get it? · what each purification step removes

Think of cleaning a muddy pair of trainers before putting them away. You rinse off the mud, then wipe off the soapy water, then leave them to dry, then pick off the last few bits of grit by hand. Each step removes a different kind of dirt, and none of the steps would do the whole job alone.

Purifying an organic liquid works the same way:

1. The crude liquid contains four kinds of "dirt": acid, other water-soluble impurities, dissolved water, and other organic compounds.
2. Shaking with an aqueous solution in a separating funnel washes out anything that dissolves in water. Sodium hydrogencarbonate also reacts with the acid.
3. Separating the layers removes the aqueous solution, but a little water is still dissolved in the organic layer. That is why it looks cloudy.
4. The anhydrous salt soaks up that last water. Now the liquid is clear.
5. Organic impurities mix completely with the organic product, so washing with water cannot remove them. Only their different boiling points can separate them, which is what redistillation uses.

In exam wording: the separating funnel removes the aqueous layer; NaHCO₃ neutralises acid; the anhydrous salt (MgSO₄ or CaCl₂) dries the organic layer; redistillation collects the product at its boiling point, separating it from organic impurities.

PAG5: synthesis of an organic liquid

PAG5 is OCR's practical activity group for making and purifying an organic liquid. The spec's example is the synthesis of a haloalkane, and it covers heating under reflux, purification using a separating funnel, distillation and a risk assessment.

A typical example is making 1-bromobutane from butan-1-ol, using the substitution reaction from 4.2.1. Sodium bromide and sulfuric acid make HBr in the flask, and the HBr substitutes for the OH group:

NaBr + H₂SO₄ → NaHSO₄ + HBr

CH₃CH₂CH₂CH₂OH + HBr → CH₃CH₂CH₂CH₂Br + H₂O

Two things that catch students out in this prep:

• 1-bromobutane is denser than water (about 1.27 g cm^-3), so in the separating funnel it is the lower layer.
• A risk assessment matters: concentrated sulfuric acid is corrosive, and the organic liquids are flammable, so heat electrically and keep the apparatus open to the air.

Synthetic routes: identifying functional groups

Functional group: a group of atoms responsible for the characteristic reactions of a compound.

In a molecule with several functional groups, find each group first. You are expected to recognise every functional group met in Module 4:

For an alcohol or a haloalkane, also decide whether it is primary, secondary or tertiary, because that changes what it can do. A tertiary alcohol, for example, cannot be oxidised by acidified dichromate.

Synthetic routes: predicting properties and reactions

Once you have found the groups, treat each functional group as reacting in the way you already know, with the reagents you know for it. Groups that have no reaction with a reagent are left unchanged.

For 1-chloropent-4-en-2-ol, CH₂=CHCH₂CH(OH)CH₂Cl:

Properties can be predicted the same way. The -OH group can hydrogen bond, so this compound is less volatile and more soluble in water than a hydrocarbon of similar size.

Synthetic routes: the Module 4 reaction toolkit

These are all the transformations between functional groups that you know at this point in the course. Learn the reagents and the conditions for each: in a route question, both are usually needed.

Gaps and dead ends in the Module 4 toolkit, which shape your routes:

• No one-step route from a haloalkane to an alkene. Go via the alcohol: haloalkane → alcohol → alkene.
• Ketones and carboxylic acids are end points at this stage. Their further reactions come in Module 6.
• An aldehyde is only an end point or a stop on the way to the acid. Oxidising an isolated aldehyde is A level content (6.1.2).
• Tertiary alcohols cannot be oxidised.
• None of these reactions changes the carbon skeleton, so the start and target have the same number of carbon atoms in the same arrangement.
• Radical substitution is a poor way to make a specific haloalkane: it gives a mixture of products, by further substitution and by substitution at different positions in the chain. Make haloalkanes from an alkene (with HX) or an alcohol (with NaBr/H₂SO₄) instead.

The exam may give you extra information about a reaction you have not met. Treat it as one more arrow in the toolkit and use it in the route.

Synthetic routes: devising a two-stage route

A two-stage route converts a starting compound into a target through one intermediate. Work through it like this:

1. Identify the functional group in the starting compound and in the target.
2. Check the carbon skeleton is the same. It must be, with this toolkit.
3. Work backwards from the target: which functional group can be turned into the target in one step?
4. Check forwards: can the starting compound be turned into that intermediate in one step?
5. For each stage, write the reagents, the conditions, and the name or structure of the intermediate. Add equations if they are asked for.

Still don't get it? · working backwards to plan a route

Imagine planning a train journey from your town to a city with no direct train. You would not pick a train at random and hope. You look at the city first, find which stations have a direct train into it, and then check which of those stations you can reach directly from home. That station is where you change.

A synthesis route is the same idea:

1. The target is the city. The starting compound is home.
2. The toolkit table is the timetable: each row is one direct train between two functional groups.
3. Look up every row that ends at the target's functional group. Each one gives a possible "change station" (intermediate).
4. For each possible intermediate, look for a row that starts at your starting compound's functional group and ends at it.
5. The intermediate that appears in both lists is your route. If none does, you need more than two stages, or the exam has given you an extra reaction to use.

For example, to turn 1-bromopropane into propanal: the only row ending in an aldehyde starts from a primary alcohol. Can 1-bromopropane become propan-1-ol in one step? Yes, by hydrolysis. So the intermediate is propan-1-ol.

In exam wording, give each step's reagent, conditions and the intermediate: "Stage 1: NaOH(aq), heat under reflux, forms propan-1-ol. Stage 2: K₂Cr₂O₇/H₂SO₄, heat and distil, forms propanal."

Worked examples

1. Two-stage route: 1-bromopropane to propanal

Plan. Target: aldehyde. Only a primary alcohol gives an aldehyde, so the intermediate is propan-1-ol. 1-bromopropane is a haloalkane, and haloalkanes hydrolyse to alcohols. Both stages exist, and the carbon chain stays at three carbons.

Stage 1: NaOH(aq), heat under reflux. Intermediate: propan-1-ol.

CH₃CH₂CH₂Br + NaOH → CH₃CH₂CH₂OH + NaBr

Stage 2: K₂Cr₂O₇/H₂SO₄, heat and distil off the propanal as it forms.

CH₃CH₂CH₂OH + [O] → CH₃CH₂CHO + H₂O

Where marks go: "distil" is the condition that stops the oxidation at the aldehyde. Writing "heat under reflux" here gives propanoic acid instead, and loses the mark.

2. Two-stage route: ethene to ethanoic acid

Plan. Target: carboxylic acid. It comes from a primary alcohol with excess oxidising agent under reflux, so the intermediate is ethanol. Ethene becomes ethanol by hydration.

Stage 1: steam with an H₃PO₄ catalyst (high temperature and pressure). Intermediate: ethanol.

CH₂=CH₂ + H₂O ⇌ CH₃CH₂OH

Stage 2: excess K₂Cr₂O₇/H₂SO₄, heat under reflux.

CH₃CH₂OH + 2[O] → CH₃COOH + H₂O

Check the [O] count: going from CH₃CH₂OH to CH₃COOH removes 2 H (as water) and adds 1 O, which needs 2[O].

3. Two-stage route: cyclohexanol to 1,2-dibromocyclohexane

Plan. Target: a dihaloalkane with the two Br atoms on neighbouring carbons. That pattern comes from adding Br₂ across a C=C, so the intermediate is cyclohexene. An alcohol becomes an alkene by elimination of water.

Stage 1: acid catalyst (conc. H₃PO₄ or conc. H₂SO₄), heat. Intermediate: cyclohexene.

C₆H₁₁OH → C₆H₁₀ + H₂O

Stage 2: Br₂ at room temperature.

C₆H₁₀ + Br₂ → C₆H₁₀Br₂

Why not NaBr/H₂SO₄ on the alcohol? That swaps OH for one Br, giving bromocyclohexane, not the dibromo compound.

4. Percentage yield of a prepared liquid

This uses the percentage yield method from Amount of substance, applied to the PAG5 preparation.

Task: 7.40 g of butan-1-ol is converted into 1-bromobutane using excess NaBr and H₂SO₄. After purification, 6.50 cm³ of 1-bromobutane is collected. The density of 1-bromobutane is 1.27 g cm^-3. Calculate the percentage yield.

C₄H₉OH + HBr → C₄H₉Br + H₂O (1 : 1 ratio)

Step 1: molar masses (relative atomic masses from the data sheet).

$M(\text{C}_4\text{H}_9\text{OH}) = (4 \times 12.0) + (10 \times 1.0) + 16.0 = 74.0 \text{ g mol}^{-1}$

$M(\text{C}_4\text{H}_9\text{Br}) = (4 \times 12.0) + (9 \times 1.0) + 79.9 = 136.9 \text{ g mol}^{-1}$

Step 2: amount of the limiting reagent. The other reagents are in excess, so butan-1-ol sets the maximum yield.

$n(\text{C}_4\text{H}_9\text{OH}) = \frac{7.40 \text{ g}}{74.0 \text{ g mol}^{-1}} = 0.100 \text{ mol}$

Step 3: theoretical mass of product (1 : 1 ratio, so 0.100 mol of 1-bromobutane).

$m_{\text{theoretical}} = 0.100 \text{ mol} \times 136.9 \text{ g mol}^{-1} = 13.69 \text{ g}$

Step 4: actual mass from the volume collected.

$m_{\text{actual}} = 6.50 \text{ cm}^3 \times 1.27 \text{ g cm}^{-3} = 8.255 \text{ g}$

Step 5: percentage yield.

$\text{percentage yield} = \frac{8.255 \text{ g}}{13.69 \text{ g}} \times 100 = 60.3\%$

The data are all to 3 significant figures, so the answer is given to 3 significant figures: 60.3%.

Where marks are dropped:

• Using the volume (6.50) as if it were a mass. Convert with density first: mass = volume × density.
• Working from the moles of NaBr or H₂SO₄. They are in excess, so they do not limit the yield.
• Dividing the wrong way up. Theoretical ÷ actual gives 166%, and a yield above 100% is impossible, so it is a quick check.

Common exam mistakes

• Drawing the reflux condenser sealed at the top, or with a bung in it. It must be open; heating a sealed system builds up pressure.
• Water in at the top of the condenser. Water goes in at the bottom and out at the top.
• Thermometer bulb in the liquid during distillation. It goes level with the side-arm, to read the temperature of the vapour being collected.
• Explaining reflux as "to stop it boiling over" or just "to heat it". Say the vapours condense and return to the flask, so the mixture can be heated for a long time without losing volatile reactants or products.
• Assuming the organic layer is always on top. The denser layer is at the bottom; bromo- and iodoalkanes such as 1-bromobutane are often denser than water.
• Forgetting to release the pressure when washing with NaHCO₃(aq). It produces CO₂.
• Writing "MgSO₄ solution" as the drying agent. It must be the anhydrous solid. The sign that the liquid is dry is that it turns clear.
• Saying redistillation "removes water". The drying agent removes water; redistillation separates the product from organic impurities by collecting it at its boiling point.
• Giving a reagent without its conditions in a route, e.g. "K₂Cr₂O₇" with no acid and no "distil" or "reflux", or "NaOH" without aqueous and reflux.
• Mixing up distil and reflux for oxidation: distil for the aldehyde, reflux (with excess oxidising agent) for the carboxylic acid or the ketone.
• Not naming the intermediate. A two-stage route needs the compound made in stage 1, by name or structure.
• Oxidising a tertiary alcohol in a route. Tertiary alcohols do not react with acidified dichromate.
• Choosing radical substitution of an alkane to make one particular haloalkane. It gives a mixture of products; use an alkene with HX, or an alcohol with NaBr/H₂SO₄.
• Changing the number of carbon atoms between start and target. None of the reactions in the toolkit table makes or breaks a C-C bond in the chain.

Key definitions

• Functional group: a group of atoms responsible for the characteristic reactions of a compound.
• Heating under reflux: heating a mixture with a vertical condenser so that vapours condense and return to the flask, allowing prolonged heating without loss of volatile substances.
• Distillation: heating a mixture so that a volatile component boils off, is condensed and is collected separately.
• Redistillation: distilling a crude product a second time and collecting only the fraction that boils close to the product's boiling point, to separate it from organic impurities.
• Quickfit apparatus: glassware with ground-glass joints that fit together without bungs, so it can be assembled for reflux or distillation.
• Immiscible: describes two liquids that do not mix, so they form separate layers.
• Drying agent: an anhydrous salt (e.g. MgSO₄ or CaCl₂) that removes water from an organic liquid.
• Two-stage synthetic route: a sequence of two reactions that converts a starting compound into a target compound through one intermediate.

Specification

• I can draw and label Quickfit apparatus for heating under reflux and for distillation, and explain when each is used. (4.2.3 a i)
• I can describe how to use a separating funnel to remove an organic layer from an aqueous layer, and decide which layer is which from density. (4.2.3 a ii)
• I can describe drying an organic liquid with an anhydrous salt (e.g. MgSO₄, CaCl₂), and how to tell when it is dry. (4.2.3 a ii)
• I can explain why the product is redistilled and which fraction is collected. (4.2.3 a ii)
• I can outline the preparation and purification of an organic liquid such as a haloalkane, giving a reason for each step. (4.2.3 a, PAG5)
• I can identify every Module 4 functional group in a molecule that contains several of them. (4.2.3 b i)
• I can predict the properties and the reactions of a molecule with several functional groups, including which group reacts with a given reagent. (4.2.3 b ii)
• I can devise a two-stage synthetic route between Module 4 functional groups, giving reagents, conditions and the intermediate, and use extra reactions given in a question. (4.2.3 c)

Related notes

• Amount of substance: percentage yield calculations
• Basic concepts of organic chemistry: naming compounds and functional groups
• Alkanes: radical substitution and why it gives a mixture
• Alkenes: addition reactions of alkenes
• Alcohols: oxidation, elimination and substitution of alcohols
• Haloalkanes: hydrolysis of haloalkanes
• Analytical techniques: using IR spectra to check what you have made
• Organic synthesis (A level): longer routes, solid preparations and the full A level toolkit