6.8 Organic Synthesis

This question is about a drug called mesalamine (also known as 5-aminosalicylic acid) that is used to treat bowel disease. It can be synthesised from salicylic acid, the chemical structure of which is shown below:

State the systematic IUPAC name for salicylic acid and deduce how many positional isomers are possible, giving their names and structures.

A possible two step synthesis of mesalamine is shown below.

Complete the flowchart showing the structures of compound B and mesalamine.

What reagents and conditions are needed to convert:

Give the structures of compound C and the compound D(repeat unit).

Chloroquine is antimalarial drug that was briefly trialed during the Covid-19 pandemic, but not found to be effective in treating SARS-CoV-2 infections. It can be synthesised from 4,7-dichloroquinoline. The structures of the two compounds are shown below.

Determine the molecular formula of 4,7-dichloroquinoline and chloroquine.

Deduce the type of reaction taking place and write the formula of the co-product of the reaction that converts 4,7-dichloroquinoline into chloroquine.

Organic molecules have to be highly purified for use as pharmaceutical drugs. Suggest how the purity of a sample of chloroquine can be determined after synthesis from 4,7-dichloroquinoline.

Ethyl 4-aminobenzoate, shown in Figure 1, is more commonly known as benzocaine. It is an ester based compound that is used medicinally as a local anaesthetic in pain relievers and cough drops.

Figure 1

One of the first industrial processes to manufacture benzocaine was the multi-step reaction shown in Figure 2.

Figure 2

The current cost of >99.7% pure benzene is around £10.00 per litre compared to > 99.5% pure methylbenzene at a cost of around £7.00 per litre.

Explain why it would be beneficial to start from methylbenzene instead of benzene in the manufacture of benzocaine. Your answer should not include economic considerations.

Concentrated sulphuric acid and concentrated nitric acid are used to form the nitronium ion required for step 2 of the reaction scheme, in part (a).

The following equilibrium is the first step in the formation of the nitronium ion.

H₂SO₄ + HNO₃ ⇋ HSO₄^- + H₂NO₃⁺

Give the reagents and conditions necessary for steps 4 and 5 of the reaction scheme shown in part (a).

A student suggests the reaction scheme shown in Figure 3 as an alternative to the original industrial reaction scheme shown in part (a) for the production of benzocaine.

Figure 3

A student is asked to prepare a sample of propyl propanoate using propanal.

Suggest a reaction scheme, using displayed formulae, that the student could use to prepare their sample of propyl propanoate.

Conditions and reagents are not required.

Use your answer from part (a) to help answer this question.

One of the intermediates in the reaction scheme, from part (a), has a molecular mass of 74.0 g mol-1.

Propanal and the intermediate (M_r = 74.0) in the reaction scheme, from part (a), are to be separated by distillation.

Explain which chemical will distill first.

Use your answer from part (a) to help answer this question.

One of the intermediates in the reaction scheme, from part (a), has a molecular mass of 60.0 g mol-1. 

Propanone can be synthesised from 2-bromopropane according to the reaction scheme shown in Figure 1. 

Figure 1

Step 1 is not completed in acidic conditions.

Give the reagents and conditions for steps 2 and 3 of the reaction scheme in part (a).

Suggest one reaction to replace steps 1 and 2 in the part (a) reaction scheme.

To prepare a sample of ethanal, a student adapts the reaction scheme from part (a). The student’s adapted reaction scheme is shown in Figure 2.

Figure 2

Explain one improvement the student should make to their adapted reaction scheme.

Outline how ethanal can be synthesised from ethane in three steps.

State the reaction conditions and reagents and name the type of reaction taking place.

The following reaction pathway is used to produce Compounds A and B, which when reacted together, form a branched ester molecule, Compound C. 

Suggest suitable reagents and conditions for the synthesis of Compound A via Step 1 and give the name for this type of reaction.

The ketone in part (a), must be converted to compound B to produce the ester.

Draw the skeletal formula of the ester formed from the reaction scheme.

1-(3-Aminophenyl)ethanol can be synthesised according to the following three-step reaction scheme.

Step 1 involves a reaction at position 3 of the benzene ring of 1-phenylethan-1-one.

State the reaction type, including suitable reagents, for Step 1.

Step 2 involves changes to the ketone group.

State a suitable reagent for Step 2.

In Step 3 of the reaction scheme, compound C is heated with hydrochloric acid in the presence of a tin catalyst to form the final product, 1-(3-aminophenyl)ethanol. 

Explain why Step 3 is a reduction reaction.

Suggest a reaction scheme, using displayed formulae, that could be used to prepare a sample of propyl propanoate from one reactant. 

Conditions and reagents are not required.

One of the intermediates in the reaction scheme has a molecular mass of 74.0 g mol^-1.

Propanal and the intermediate (M_r = 74.0) in the reaction scheme are to be separated by distillation.

Explain which chemical will distil off first.

One of the intermediates in the reaction scheme has a molecular mass of 60.0 g mol^-1. 

Aspirin is a medicine used to relieve pain and reduce fever.

A student prepares a sample of aspirin, HOOCC₆H₄OCOCH_3, from salicylic acid, HOOCC₆H₄OH.

The student makes aspirin by warming 7.5 g of salicylic acid with 15.0 cm³ of ethanoic anhydride, (CH₃CO)₂O, in the presence of concentrated sulfuric acid.

Write a balanced equation, using structural formulae, for this reaction.

The density of ethanoic anhydride is 1.10 g cm^–3.

Deduce whether the salicylic acid or ethanoic anhydride is in excess. 

The student transfers their hot solution into water and impure aspirin crystallises out as the water cools.

The student then purifies the aspirin by recrystallisation.

State the properties of a suitable solvent for recrystallisation. 

After recrystallisation, the student obtained 5.91 g of aspirin.

Calculate the student's percentage yield.