Organic Synthesis Practical Methods and Procedures

Making a new organic compound in the laboratory is never just "mix two chemicals together." A real synthesis is a sequence of practical steps: heating the reaction safely, isolating the product, purifying it, drying it, and finally checking that it is actually pure and working out how efficient the reaction was. This page pulls together the core practical methods and procedures that come up again and again in A Level organic synthesis questions.

Many organic reactions (for example, oxidising an alcohol, or hydrolysing an ester) need prolonged heating to go to completion, but the reactants and products are often volatile and flammable. Heating an open flask would simply boil the mixture away. Instead, chemists heat under reflux: the reaction flask is fitted with a vertical condenser open at the top, so any vapour rising from the boiling mixture is cooled, condenses back into liquid, and drips back into the flask. This lets the mixture be heated continuously and safely for as long as the reaction needs, without loss of volatile material.

Anti-bumping granules are usually added to keep the boiling smooth, and the top of the condenser is left open to the air (not sealed), so that pressure never builds up inside the apparatus.

Once a reaction is complete, distillation is used to separate a liquid product from the reaction mixture, based on differences in boiling point. In simple distillation, the mixture is heated, vapour rises and passes into a condenser angled downward, and the condensed liquid (the distillate) is collected in a separate flask. A thermometer positioned at the side arm monitors the temperature of the vapour, which should stay close to the boiling point of the product being collected. Where two liquids have similar boiling points, fractional distillation is used instead, adding a fractionating column packed with glass beads or rings to give repeated condensation and re-evaporation, improving separation.

Solid organic products are usually purified by recrystallisation rather than distillation. The impure solid is dissolved in the minimum volume of a hot solvent in which it is soluble when hot but only slightly soluble when cold. The hot solution is filtered (if needed) to remove insoluble impurities, then left to cool slowly, so the desired compound crystallises out while soluble impurities remain dissolved in the mother liquor. The crystals are collected by filtration under reduced pressure, washed with a small amount of cold solvent, and dried. Choosing the right solvent is essential: if the compound is too soluble even when cold, none will crystallise; if it is too insoluble even when hot, too little will dissolve to begin with.

When an organic product is present in an aqueous reaction mixture, it can be separated by shaking the mixture with an immiscible organic solvent in a separating funnel. The two layers form: the organic layer sits on top if it is less dense than water, or underneath if it is denser. After allowing the layers to settle, the tap is opened to run off the lower layer, leaving the upper layer in the funnel. This step is often repeated, and the combined organic extracts are then dried and, if the product is a liquid, purified further by distillation.

Traces of water left in an organic liquid are removed using a solid drying agent, such as anhydrous calcium chloride or magnesium sulfate, which must not react with the product itself. The drying agent is added, the mixture is swirled and left to stand, and the solid is then removed by filtration or by decanting the liquid away from it, ready for final purification by distillation.

A pure organic solid has a sharp, narrow melting point that matches a known literature value; an impure sample melts over a broader range and at a lower temperature. Thin layer chromatography (TLC) gives further evidence of purity: a pure compound produces a single spot with a characteristic retention factor, while an impure sample shows multiple spots. Where a synthesis produces a chiral product, techniques for distinguishing the two forms link closely to the ideas covered in chirality and optical isomers.

No synthesis converts 100% of the starting material into product, because reactions can be reversible, side reactions can occur, and some product is always lost during purification steps such as recrystallisation and filtration. The efficiency of a preparation is measured using percentage yield:

\( \eta = \dfrac{m_{actual}}{m_{theoretical}} \times 100 \)

where \( m_{actual} \) is the mass of product actually obtained and \( m_{theoretical} \) is the maximum possible mass calculated from the balanced equation and the limiting reagent.

Worked example

An ester is prepared from a carboxylic acid and an alcohol, and the calculated theoretical mass of ester is 8.5 g. After purification, 6.2 g of pure ester is collected. The percentage yield is \( \eta = \dfrac{6.2}{8.5} \times 100 = 72.9 \). This type of preparation, along with the reagents and mechanism involved, is covered in detail in carboxylic acids, acyl chlorides and esters. Similar reflux, distillation and purification steps are also used when preparing carbonyl compounds, discussed in aldehydes and ketones.

A typical synthesis question expects you to sequence these techniques correctly: reflux to carry out the reaction, extraction or distillation to isolate the crude product, recrystallisation or further distillation to purify it, drying to remove water, and melting point or TLC to confirm purity, before finally calculating a percentage yield. Recognising which technique fits which stage, and why, is the practical skill examiners are testing.

Related lessons

• Uk A Level Chemistry