# Chemical Synthesis and Design

> How chemists design a way to make a product, weighing yield, purity, rate, cost, energy, safety, waste and environmental impact, with case studies from industry and green chemistry.

From HSC Chemistry on WhizzNotes, free study notes for NSW students: https://whizznotes.com/chemistry/chemical-synthesis-and-design/. Updated 3 November 2026.
Year 11 and Year 12 boxes go deeper than the Year 10 text around them.

### Story time: Two ways to make a painkiller
In the 1960s, the painkiller ibuprofen was made in six steps. More than half the mass of the chemicals used ended up as waste. In the 1990s, a company designed a new route with only three steps. Almost all of the starting atoms ended up in the medicine, and the one by-product could be reused.

The medicine was exactly the same. What changed was the **design** of the process: fewer steps, less waste, less energy, lower cost. Chemical synthesis is about more than getting a reaction to work. It is about making a product safely, cheaply and cleanly, at a huge scale.

**In short:** Designing a chemical synthesis means choosing a route and conditions that balance yield, rate, purity, cost, energy, safety and waste. The Haber process for ammonia uses a compromise temperature, high pressure and a catalyst, and green chemistry aims for high atom economy and less waste.

## What is chemical synthesis?

**Chemical synthesis** is making a wanted product from starting materials (reactants) through one or more reactions. Industrial chemists must consider many factors at once.

## Factors in designing a synthesis

| Factor | Questions to ask |
|---|---|
| **Reactants** | Are they available, cheap and renewable? Are they safe to store and transport? |
| **Yield** | How much product forms compared with the theoretical maximum? Is it an equilibrium? |
| **Rate** | Is it fast enough? Is a catalyst available? |
| **Purity** | How pure must the product be (a medicine must be very pure)? How will it be separated? |
| **Energy** | High temperatures and pressures cost money and need strong equipment. |
| **By-products and waste** | Can by-products be sold or reused? How is waste disposed of? |
| **Safety** | Are any chemicals toxic, flammable or explosive? Are conditions dangerous? |
| **Environment** | What is released to air, water and land? Is the process sustainable? |
| **Economics** | Capital cost of building the plant, running costs (chemicals, energy, labour), and the value of the products. |
| **Social** | Jobs, local community, benefits of the product. |

## Using equilibrium and rate together

Many industrial reactions are **reversible**. Chemists use Le Chatelier's principle and collision theory to choose conditions:

- **Temperature**: for an exothermic reaction, a low temperature gives a better yield but a slow rate. A **compromise** temperature and a **catalyst** are used.
- **Pressure**: high pressure favours the side with fewer gas moles and also speeds up gas reactions, but costs more and is riskier.
- **Concentration**: using an **excess** of a cheap reactant, or **removing** the product, pushes the equilibrium right.

### Worked example: The Haber process
$\mathrm{N_2(g)} + \mathrm{3H_2(g)} \rightleftharpoons \mathrm{2NH_3(g)}$, $\Delta H = -92$ kJ/mol

- **About 450 °C**: lower would give more ammonia but far too slowly.
- **About 200 atm**: shifts right to fewer gas moles; higher would cost too much.
- **Iron catalyst**: speeds up reaching equilibrium.
- Ammonia is **cooled and removed** as a liquid, and unreacted gases are **recycled**, so overall conversion reaches about 98%.

Ammonia is made into fertilisers that help feed billions of people.

### Worked example: Making sulfuric acid (the Contact process)
The key step is $\mathrm{2SO_2(g)} + \mathrm{O_2(g)} \rightleftharpoons \mathrm{2SO_3(g)}$, $\Delta H < 0$.

- About 450 °C, a compromise between yield and rate.
- Just over 1 atm: the yield is already over 95%, so high pressure is not worth the cost.
- Vanadium(V) oxide catalyst.
- Excess air (oxygen) pushes the equilibrium right.

## Choosing between routes

When two processes make the same product, compare them fairly:

| Compare | Better route has |
|---|---|
| Yield and purity | More product, purer |
| Costs | Lower capital and running costs, longer plant lifetime |
| Energy | Lower temperatures and pressures |
| By-products | Useful, saleable by-products rather than waste |
| Environment | Less toxic waste, fewer emissions |

For example, phenol can be made from benzene through chlorobenzene (producing waste NaCl and HCl) or by the **cumene process** (producing propanone, which can be sold as a solvent). The cumene route has higher yield and purity, lower energy costs and a useful by-product.

## Green chemistry

**Green chemistry** aims to design processes that are safer and produce less waste. Its ideas include:

- **Prevent waste** rather than clean it up.
- **High atom economy**: as many reactant atoms as possible end up in the product.
- Use **renewable** raw materials.
- Use **catalysts** instead of large amounts of reagents.
- Use **safer solvents** (like water) and lower temperatures.
- Design products that **break down** safely after use.

## Scale and monitoring

A reaction that works in a test tube must be **scaled up**. In a large reactor:

- Heat from exothermic reactions builds up and must be removed, or the reaction can run out of control.
- Mixing is harder.
- Conditions (temperature, pressure, concentrations, pH) are **monitored** constantly with sensors.

Chemists also analyse samples of the product (using techniques from the last two chapters) to check its **purity**.

**Mind map**

```text
Synthesis and design
  Factors
    Reactants and cost
    Yield and purity
    Rate and catalysts
    Energy
    Safety
    Waste and environment
  Equilibrium choices
    Compromise temperature
    Pressure
    Excess reactant
    Remove product
  Case studies
    Haber: ammonia
    Contact: sulfuric acid
    Cumene: phenol
  Green chemistry
    Atom economy
    Renewable materials
    Less waste
  Scale up
    Heat removal
    Monitoring
```

### Year 11: Percentage yield over several steps
Each step of a synthesis loses some product, so overall yield falls quickly.

$$\text{overall yield} = \text{yield}_1 \times \text{yield}_2 \times \ldots$$

Three steps with yields of 80%, 70% and 90% give $0.80 \times 0.70 \times 0.90 = 0.504$, or about **50%**. This is why chemists try to design routes with **fewer steps**.

**Fewer steps can win even with lower yields.** Six steps at 85% give $0.85^6 = 0.38$ (38%). Three steps at 75% give $0.75^3 = 0.42$ (42%).

**Comparing costs.** Work out the cost per tonne over the plant's whole life: (build cost + yearly cost × years) ÷ (tonnes per year × years). The cheaper per tonne usually wins, but also weigh safety, waste and energy.

### Year 12: Atom economy
**Atom economy** measures how much of the reactants' mass ends up in the **wanted product**:

$$\text{atom economy} = \frac{\text{molar mass of wanted product}}{\text{total molar mass of all reactants}} \times 100$$

**Example.** Making ethanol by hydration: $\mathrm{C_2H_4} + \mathrm{H_2O} \rightarrow \mathrm{C_2H_5OH}$. All atoms end up in ethanol, so the atom economy is **100%**.

Making ethanol by fermentation: $\mathrm{C_6H_{12}O_6} \rightarrow \mathrm{2C_2H_5OH} + \mathrm{2CO_2}$.

Atom economy $= \dfrac{2 \times 46.07}{180.16} \times 100 = 51\%$. Almost half the mass leaves as $\mathrm{CO_2}$.

**Addition reactions** always have 100% atom economy. **Substitution** and **elimination** reactions always make a by-product, so they are lower. Note that atom economy is not the same as yield: a reaction can have a high yield but a low atom economy.

**With a by-product.** Esterification makes water too. Ethanoic acid (60.05) + ethanol (46.07) gives ethyl ethanoate (88.11): atom economy $= \dfrac{88.11}{60.05 + 46.07} \times 100 = 83\%$.

## Quick summary

- Synthesis design weighs reactants, yield, rate, purity, energy, safety, waste, environment and cost.
- For equilibria, use a compromise temperature, a catalyst, suitable pressure, excess reactant and product removal.
- Haber (ammonia) and Contact (sulfuric acid) processes show these choices.
- Compare routes by yield, purity, cost, energy, by-products and environmental impact.
- Green chemistry: prevent waste, high atom economy, renewable raw materials, catalysts, safer solvents.

## Quiz

Try these questions from the chapter quiz.

1. Chemical synthesis means:
   - A. Making a product from reactants by chemical reactions
   - B. Separating a mixture
   - C. Measuring a concentration
   - D. Testing for ions
   - Answer: A. Making a product from reactants by chemical reactions. Synthesis builds new substances.

2. Why do industries often use a compromise temperature for exothermic equilibria?
   - A. To increase $K$
   - B. Low temperatures give good yield but a slow rate
   - C. High temperatures give the best yield
   - D. Catalysts only work at one temperature
   - Answer: B. Low temperatures give good yield but a slow rate. The temperature balances yield against rate.

3. A catalyst is used in industry mainly to:
   - A. Increase the equilibrium yield
   - B. Speed up the reaction so equilibrium is reached faster
   - C. Change $\Delta H$
   - D. Make the product purer
   - Answer: B. Speed up the reaction so equilibrium is reached faster. It lowers the activation energy.

The whole chapter quiz is on the page, for signed-in students: https://whizznotes.com/chemistry/chemical-synthesis-and-design/#quiz