📚 Case Study in Action: Aspirin Synthesis and Analysis | 案例分析实战演练：阿司匹林的合成与测定
Aspirin is one of the most widely used medications in the world, yet its synthesis and quality control rely on fundamental chemical principles taught at Year 12. This case study guides you through a realistic laboratory scenario — from preparing aspirin by esterification to verifying purity using spectroscopic and titrimetric methods. You will practise essential skills in mole calculations, recrystallisation, infrared spectroscopy and back titration, all aligned with the WJEC A Level Chemistry specification. By working through the data and reasoning behind each step, you will deepen your understanding of how chemistry is applied to produce a safe, effective pharmaceutical product.
阿司匹林是全球使用最广泛的药物之一，但它的合成与质量控制依赖于 Year 12 所教授的基础化学原理。本案例研究将带领你经历一个真实的实验室场景——从通过酯化反应制备阿司匹林，到运用光谱和滴定方法验证纯度。你将练习摩尔计算、重结晶、红外光谱和返滴定等核心技能，所有这些都与 WJEC A Level 化学大纲紧密贴合。通过每一步的数据和推理，你将深刻理解化学如何被用来生产安全有效的药物产品。
1. Background and Reaction Scheme | 背景与反应方程式
Aspirin (2‑ethanoyloxybenzenecarboxylic acid) is an ester formed from salicylic acid and ethanoic anhydride. The phenol group on salicylic acid acts as the alcohol component, while ethanoic anhydride provides the acyl group. Concentrated sulfuric or phosphoric acid is used as a catalyst. The reaction is an example of nucleophilic addition–elimination, producing aspirin and ethanoic acid as a by‑product. The balanced equation is:
C₇H₆O₃ + C₄H₆O₃ → C₉H₈O₄ + CH₃COOH
阿司匹林（2‑乙酰氧基苯甲酸）是由水杨酸和乙酸酐形成的酯。水杨酸上的酚羟基充当醇组分，乙酸酐提供酰基。浓硫酸或磷酸用作催化剂。该反应属于亲核加成‑消除反应，生成阿司匹林和副产品乙酸。配平后的方程式为：
C₇H₆O₃ + C₄H₆O₃ → C₉H₈O₄ + CH₃COOH
2. Experimental Procedure: Synthesis | 实验步骤：合成
In a typical preparation, 2.0 g of salicylic acid is placed in a 100 cm³ conical flask. Then 5.0 cm³ of ethanoic anhydride (density 1.08 g cm⁻³) is added, followed by 5–8 drops of concentrated phosphoric acid. The mixture is swirled and heated on a water bath at 60–70 °C for about 20 minutes. The flask is then cooled in an ice bath to precipitate the crude aspirin. After adding ice‑cold water, the solid is collected by vacuum filtration and washed with a little chilled distilled water.
在典型制备中，将 2.0 g 水杨酸放入 100 cm³ 锥形瓶中。然后加入 5.0 cm³ 乙酸酐（密度 1.08 g cm⁻³），再滴加 5–8 滴浓磷酸。振荡混合物并在 60–70 °C 水浴上加热约 20 分钟。随后将锥形瓶在冰浴中冷却，使粗阿司匹林析出。加入冰冷的蒸馏水后，用真空抽滤收集固体，并以少量冷冻蒸馏水洗涤。
3. Purification by Recrystallisation | 重结晶提纯
The crude aspirin is transferred to a beaker and dissolved in the minimum volume of boiling ethanol. Hot water is added dropwise until slight cloudiness persists, then the solution is allowed to cool slowly to room temperature before being placed in ice. Fine white needles of pure aspirin crystallise out. These are collected by vacuum filtration, washed with a little ice‑cold ethanol/water mixture, and dried between filter papers. This process removes unreacted starting materials and most coloured impurities.
将粗阿司匹林转移至烧杯中，用最小体积的沸腾乙醇溶解。逐滴滴加热水直至溶液保持轻微浑浊，然后让溶液缓慢冷却至室温，再置于冰中。纯阿司匹林呈白色针状结晶析出。通过真空抽滤收集，用少量冷冻乙醇/水混合物洗涤，并在滤纸之间干燥。此过程去除了未反应的原料和大部分有色杂质。
4. Yield Calculation: Theoretical and Percentage | 产率计算：理论与百分比
To assess the efficiency of the synthesis, we first identify the limiting reagent. The mass of salicylic acid used is 2.0 g, giving 2.0 / 138.12 = 0.01448 mol. The mass of ethanoic anhydride is 5.0 × 1.08 = 5.4 g, corresponding to 5.4 / 102.09 = 0.0529 mol – clearly in excess. The theoretical yield of aspirin is therefore 0.01448 × 180.16 = 2.61 g. In our experiment, 1.80 g of pure aspirin was obtained after recrystallisation. The percentage yield is (1.80 / 2.61) × 100 = 69.0%. Losses during recrystallisation and incomplete reaction account for the yield being below 100%.
为了评估合成效率，我们首先确定限量试剂。所用水的杨酸质量为 2.0 g，物质的量为 2.0 / 138.12 = 0.01448 mol。乙酸酐质量为 5.0 × 1.08 = 5.4 g，相当于 5.4 / 102.09 = 0.0529 mol ——明显过量。因此阿司匹林的理论产量为 0.01448 × 180.16 = 2.61 g。在我们的实验中，重结晶后得到 1.80 g 纯阿司匹林。百分产率为 (1.80 / 2.61) × 100 = 69.0%。重结晶过程中的损失以及反应不完全导致产率低于 100%。
5. Purity Testing: Melting Point Determination | 纯度测试：熔点测定
A sharp melting point is a simple yet powerful indicator of purity. The recrystallised aspirin was placed in a melting point tube and slowly heated in an electrically controlled apparatus. The solid melted sharply at 134–136 °C, closely matching the literature value of 136 °C for pure aspirin. A broad melting range or a value significantly below 136 °C would suggest the presence of impurities, such as unreacted salicylic acid (m.p. 158 °C) or residual solvent.
敏锐的熔点是纯度的简单而有力的指标。将重结晶后的阿司匹林装入熔点管，在电控熔点仪中缓慢加热。固体在 134–136 °C 敏锐熔化，与纯阿司匹林的文献值 136 °C 非常接近。较宽的熔程或明显低于 136 °C 的熔点值则表明存在杂质，例如未反应的水杨酸（熔点 158 °C）或残留溶剂。
6. Spectroscopic Analysis: Infrared Spectroscopy | 光谱分析：红外光谱
Infrared spectroscopy was used to confirm the identity of the product. The spectrum of recrystallised aspirin displayed characteristic absorption bands, as shown in the table below. The absence of a broad O–H stretch around 2500–3300 cm⁻¹ for the carboxylic acid of salicylic acid and the appearance of an ester C=O peak provide strong evidence for successful acetylation.
红外光谱被用来确认产物身份。重结晶阿司匹林的光谱显示出特征吸收带，如下表所示。水杨酸羧基在 2500–3300 cm⁻¹ 范围内的宽 O–H 伸缩振动消失，而出现了酯羰基峰，这为乙酰化成功提供了有力证据。
| Functional Group | Wavenumber / cm⁻¹ | Appearance |
|---|---|---|
| O–H (carboxylic acid) | 2500–3300 (broad) | Strong, very broad |
| C=O (ester) | 1754 | Strong, sharp |
| C=O (carboxylic acid) | 1690 | Strong |
| C–O (ester) | 1220, 1180 | Strong |
The presence of two distinct carbonyl stretches — one from the ester and one from the carboxylic acid — is diagnostic of aspirin. The fingerprint region (below 1500 cm⁻¹) also matched a reference spectrum of pure aspirin, further confirming identity.
两个不同的羰基伸缩振动——一个来自酯，另一个来自羧酸——是阿司匹林的特征。指纹区（1500 cm⁻¹ 以下）也与纯阿司匹林的参考光谱吻合，进一步确认了身份。
7. Titration for Purity: Back Titration Method | 纯度滴定：返滴定法
Because aspirin is a weak acid and its hydrolysis in water is slow, a back titration is employed to determine its purity. A known mass of the recrystallised sample (0.50 g) is reacted with an excess of standard sodium hydroxide solution: exactly 25.0 cm³ of 0.500 mol dm⁻³ NaOH is added. The mixture is heated to ensure complete hydrolysis of the ester; each mole of aspirin consumes two moles of NaOH due to subsequent neutralisation of the phenolic group. After cooling, the unreacted NaOH is titrated against 0.500 mol dm⁻³ hydrochloric acid using phenolphthalein as indicator. The volume of HCl required neutralises the leftover base, allowing the amount of NaOH that reacted with the aspirin to be found by subtraction.
由于阿司匹林是弱酸且在水中的水解缓慢，因此采用返滴定法测定其纯度。准确称量重结晶样品 0.50 g，与过量的标准氢氧化钠溶液反应：精确加入 25.0 cm³ 0.500 mol dm⁻³ NaOH。加热混合物以确保酯完全水解；每摩尔阿司匹林消耗两摩尔氢氧化钠，因为后续酚基也被中和。冷却后，以酚酞为指示剂，用 0.500 mol dm⁻³ 盐酸滴定未反应的 NaOH。中和剩余碱所需的盐酸体积，通过差减法即可求得与阿司匹林反应的 NaOH 的量。
8. Interpretation of Back Titration Results | 返滴定结果解读
In the titration, 14.20 cm³ of 0.500 mol dm⁻³ HCl was required to reach the endpoint. Moles of HCl used = 0.01420 × 0.500 = 0.00710 mol, which equals the moles of NaOH left unreacted. The total moles of NaOH initially added = 0.0250 × 0.500 = 0.0125 mol. Therefore, moles of NaOH that reacted with the aspirin = 0.0125 − 0.00710 = 0.00540 mol. Since 1 mol of aspirin ≡ 2 mol of NaOH, the amount of aspirin in the sample = 0.00540 / 2 = 0.00270 mol. Mass of aspirin present = 0.00270 × 180.16 = 0.486 g. Purity = (0.486 / 0.500) × 100 = 97.2%.
滴定中，消耗了 14.20 cm³ 0.500 mol dm⁻³ 盐酸才能达到终点。HCl 物质的量 = 0.01420 × 0.500 = 0.00710 mol，等于未反应的 NaOH 的物质的量。初始加入的 NaOH 总物质的量 = 0.0250 × 0.500 = 0.0125 mol。因此，与阿司匹林反应的 NaOH 物质的量 = 0.0125 − 0.00710 = 0.00540 mol。由于 1 mol 阿司匹林 ≡ 2 mol NaOH，样品中阿司匹林的物质的量 = 0.00540 / 2 = 0.00270 mol。阿司匹林的质量 = 0.00270 × 180.16 = 0.486 g。纯度 = (0.486 / 0.500) × 100 = 97.2%。
A purity of 97% is acceptable for a preparation intended for laboratory demonstration, though pharmaceutical-grade aspirin requires >99.5% purity. The remaining 2.8% likely consists of trapped moisture or traces of salicylic acid that co‑crystallised.
97% 的纯度对于实验室演示制备是可以接受的，但药用级阿司匹林要求纯度 >99.5%。其余 2.8% 可能由夹带的水分或共结晶的微量水杨酸组成。
9. Error Analysis and Improvements | 误差分析与改进
Several sources of error can be identified in this case study. First, recrystallisation inevitably leaves some product dissolved in the cold solvent, lowering the yield. Using ice‑cold washing liquids and chilling thoroughly can minimise these losses. Second, during back titration, incomplete hydrolysis of aspirin would result in a higher titre of HCl and give a falsely low purity. Heating under reflux for a controlled period and checking for homogeneity ensures complete reaction. Third, transfer losses during filtration and weighing can be reduced by rinsing apparatus with small portions of solvent. Also, impurities in the NaOH or HCl solutions, if not standardised by a primary standard, could bias the final purity calculation. Implementing these improvements would bring the percentage yield and purity closer to theoretical values.
本案例研究中可以找出几种误差来源。首先，重结晶必然会有一部分产物溶解在冷溶剂中，降低产率。使用冷冻洗涤液并充分冷却可最大限度地减少这些损失。其次，返滴定过程中阿司匹林的水解不完全会导致盐酸滴定量偏高，得到虚假的低纯度。在控制时间内回流加热并检查均相状态可确保反应完全。第三，过滤和称量过程中的转移损失可通过用少量溶剂冲洗器皿来减少。另外，氢氧化钠或盐酸溶液中的杂质，如果不是用基准物质标定，会使最终纯度计算产生偏差。实施这些改进将使百分产率和纯度更接近理论值。
10. Real-World Context: Industrial Production | 现实背景：工业生产
On an industrial scale, aspirin is produced by the same acid‑catalysed acetylation but in large stainless‑steel reactors with efficient recycling of ethanoic acid and unreacted anhydride. The crude product is purified by solvent recrystallisation and, in some processes, by vacuum distillation. Quality control involves not only melting point and IR spectroscopy but also high‑performance liquid chromatography (HPLC) and potentiometric titration to ensure batch‑to‑batch consistency. Understanding the chemistry behind this common drug helps appreciate the rigorous testing that ensures consumer safety.
在工业规模上，阿司匹林采用相同的酸催化乙酰化反应生产，但在大型不锈钢反应器中进行，并高效回收乙酸和未反应的酸酐。粗产物通过溶剂重结晶进行纯化，在某些工艺中还使用真空蒸馏。质量控制不仅包括熔点和红外光谱，还用到高效液相色谱（HPLC）和电位滴定，以确保批间一致性。理解这一常用药物背后的化学，有助于领会确保消费者安全的严格检测。
11. Summary of Key Skills | 关键技能总结
Throughout this case study, you have applied a range of competences essential for WJEC Year 12 Chemistry: writing and balancing organic reaction equations, carrying out mole calculations for limiting reagents and yields, purifying solids by recrystallisation, determining melting points, interpreting infrared spectra, and employing back titration to assess purity. These analytical and practical skills form the foundation for later topics in organic synthesis, energetics and equilibrium. Revisiting the aspirin case will reinforce your confidence in tackling multi‑step problems that mirror real laboratory investigations.
通过整个案例研究，你运用了 WJEC Year 12 化学所必需的一系列能力：书写和配平有机反应方程式、进行限量试剂和产率的摩尔计算、通过重结晶提纯固体、测定熔点、解析红外光谱，以及运用返滴定评估纯度。这些分析与实践技能构成了后续有机合成、能量学和平衡等主题的基础。重温阿司匹林案例将增强你处理模拟真实实验室研究的多步骤问题的信心。
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