HSC Exam Practice

Sample response. Atom economy is the percentage of reactant atom mass (measured by molar mass) that is incorporated into the desired product. Formula: atom economy = (molar mass of desired product / sum of molar masses of all products) × 100%.

Marking notes. 1 mark for a correct definition (fraction of reactant atoms in desired product, expressed as a percentage); 1 mark for the correct formula with both numerator and denominator correctly identified.

Sample response. Reagents: salicylic acid and acetic anhydride [1]. Catalyst: acid catalyst (e.g. phosphoric acid, sulfuric acid) [1]. Products: aspirin (acetylsalicylic acid) as the desired product, and ethanoic acid (acetic acid) as the byproduct [1].

Marking notes. 1 mark for both reagents named; 1 mark for catalyst identified (accept any correct acid catalyst); 1 mark for both products named (desired product + byproduct both required for full mark on this criterion).

Sample response. Atom economy is a theoretical metric calculated from the molar masses in the balanced equation: it measures the fraction of reactant atom mass incorporated into the desired product [1]. E-factor is a practical metric: it is the mass of waste generated divided by the mass of product obtained in the actual process, and it includes solvents, auxiliaries and all other waste streams beyond those in the equation [1]. Both are useful because a route can have high atom economy (efficient reaction equation) but still have a high E-factor if large amounts of solvent or purification reagents are wasted in the process — atom economy cannot capture this [1].

Marking notes. 1 mark for defining atom economy (theoretical, molar mass ratio); 1 mark for defining E-factor (practical, waste mass / product mass); 1 mark for explaining why both are needed (atom economy cannot capture solvent/auxiliary waste; E-factor can).

Sample response. Discovery and design (identify a promising candidate molecule) [1] → preclinical testing (laboratory and animal-model testing for safety and preliminary activity) [1] → Phase I, II and III clinical trials (progressive human testing for safety, efficacy and broad confirmation) [1] → regulatory approval (formal assessment and approval by a regulatory body such as the TGA in Australia for supply). Accept a condensed version that correctly sequences discovery, preclinical, clinical trials and regulatory approval.

Marking notes. 1 mark for identifying discovery/design as the starting point; 1 mark for preclinical before clinical; 1 mark for clinical trials followed by regulatory approval as the final stage.

Sample response. A catalyst increases reaction rate and improves selectivity without being consumed in the overall reaction [1]. Because it is not consumed, it does not appear in the atom economy calculation (it is not a product), so it does not inflate product-side molar mass. However, it can reduce the energy required to drive the reaction (lower activation energy), which reduces energy waste [1]. It can also improve selectivity — steering the reaction toward the desired product and away from byproducts — which lowers the mass of waste per gram of product (lower E-factor) without changing the reaction equation itself [1].

Marking notes. 1 mark for correctly stating the catalyst is not consumed; 1 mark for explaining how it reduces energy use or improves efficiency; 1 mark for linking improved selectivity to a lower E-factor (less waste per gram of product).

Sample response. E-factor = mass of waste / mass of product = 5.1 g / 8.5 g = 0.60. This means 0.60 g of waste is generated per gram of aspirin produced.

Marking notes. 1 mark for correct substitution (5.1 / 8.5); 1 mark for correct answer (0.60; accept 0.6). Penalise if numerator and denominator are inverted (answer would be 1.67).

Sample response. Atom economy increases steadily from 63% in 2020 to 78% in 2023, a total increase of 15 percentage points [1]. E-factor decreases steadily from 5.4 in 2020 to 1.5 in 2023 — both metrics move in the direction expected for a more sustainable process [1].

Marking notes. 1 mark for describing atom economy trend with at least one data point quoted; 1 mark for describing E-factor trend with at least one data point quoted.

Sample response. % reduction = (5.4 − 1.5) / 5.4 × 100% = 3.9 / 5.4 × 100% = 72.2% (accept 72%). 1 mark method + 1 mark answer.

Sample response. Atom economy is a theoretical metric determined by the molar masses in the balanced reaction equation [1]. Changing the reaction equation to improve atom economy requires redesigning the chemistry itself — for example, finding a new reaction pathway with fewer byproduct mass — which is a difficult, time-consuming process [1]. E-factor captures process-level waste including solvents and auxiliaries, which can be reduced more readily through changes like solvent substitution, catalyst addition, or process optimisation without altering the underlying reaction. This explains why E-factor dropped by 72% (much easier process-level change) while atom economy only improved by 24% (harder, fundamental chemistry change) over the same period [1].

Marking notes. 1 mark for identifying that atom economy is a stoichiometric/theoretical metric tied to the reaction equation; 1 mark for explaining that improving it requires redesigning the chemistry (harder than process changes); 1 mark for explaining that E-factor can be reduced by process-level changes (solvent, catalyst, purification) without changing the equation.

Sample Band 6 response. Green chemistry is a design philosophy that asks chemists to minimise hazardous substances, waste and energy from the outset of synthesis, guided by 12 principles. In pharmaceutical synthesis, where large volumes of reagents and solvents are processed to produce small quantities of active ingredient, green chemistry principles have direct commercial and environmental significance.

Atom economy quantifies the theoretical efficiency of a reaction: it is the percentage of the total product-side molar mass that is the desired product. In the synthesis of aspirin from salicylic acid and acetic anhydride, one mole of each reactant produces one mole of aspirin (MM = 180 g mol−¹) and one mole of ethanoic acid (MM = 60 g mol−¹). The atom economy is therefore 180/240 × 100% = 75%. This means 25% of product-side atom mass is diverted to ethanoic acid, which must be disposed of or recovered. Improving atom economy requires changing the reaction pathway or using a different acetylating agent that produces a smaller byproduct. E-factor complements atom economy by measuring the practical waste burden: mass of waste / mass of product. A process with high atom economy but poor solvent management or excess reagents can still carry a high E-factor, as the lesson's data table illustrates (Routes A and C shared 75% atom economy but had E-factors of 2.0 and 1.0 respectively).

Solvent selection is one of the 12 Green Chemistry Principles most impactful in pharmaceutical synthesis. Replacing a halogenated solvent such as dichloromethane (high toxicity, carcinogenic potential, volatile) with water or a greener alternative directly reduces both waste toxicity and E-factor, as demonstrated by Route C in the lesson. The Sigma-Aldrich green synthesis catalogue and CSIRO green chemistry research both document solvent-substitution as a high-priority practical improvement.

Catalysis is a further key principle. Adding an acid catalyst to aspirin synthesis increases reaction rate without being consumed (does not inflate product-side molar mass), improves selectivity (fewer unwanted byproducts), and reduces required temperature — all lowering E-factor and energy waste. More advanced biocatalytic routes (e.g. immobilised lipase at ambient temperature in water) eliminate hazardous acid catalysts entirely and reduce E-factor further, as seen in Route Y of the lesson's CSIRO scenario.

In summary, green chemistry principles provide a framework for evaluating and improving synthesis at multiple levels simultaneously: the reaction equation (atom economy), the overall process waste burden (E-factor), the hazard profile (solvent selection), and the energy and reagent efficiency (catalysis). No single metric is sufficient; a holistic evaluation across principles is required. The aspirin case study shows that even a well-known, simple synthesis can be progressively improved when each principle is applied systematically.

Marking criteria (8 marks):

• 1 mark — Defines or correctly applies green chemistry as a design philosophy with reference to at least one named principle.
• 1 mark — Defines atom economy correctly (formula or description) and applies it to aspirin synthesis with a calculation or value.
• 1 mark — Defines E-factor correctly and explains how it differs from atom economy (practical vs theoretical, includes solvents/auxiliaries).
• 1 mark — Discusses solvent selection as a green chemistry principle with a specific example (named solvent change and its reason).
• 1 mark — Discusses catalysis as a green chemistry principle, explaining how a catalyst reduces waste or energy without appearing in atom economy.
• 1 mark — Uses aspirin synthesis as a concrete case study to illustrate at least two of the above principles.
• 1 mark — Demonstrates that multiple metrics/principles are required (no single measure is sufficient) with supporting reasoning.
• 1 mark — Reaches a coherent evaluative conclusion about the role of green chemistry in pharmaceutical synthesis sustainability, using precise terminology throughout.