1. The Synthesis and Analysis of Benzocaine
By Molly Winterbottom

2. Introduction
The main purpose of this experiment was to successfully synthesis Benzocaine from Nitrotoluene using methods found whilst researching how to get from Nitrotoluene to Nitrobenzoic acid, then Nitrobenzoic acid to Ethyl-4-nitrobenzoate, and finally Ethyl-4-nitrobenzoate to Ethyl-4-aminobenzoate (Benzocaine).
Those methods were then adapted to use the quantities preferred, smaller than those in the methods.
By producing TLC plates throughout each step of the synthesis of benzocaine, provides proof that the reaction has taken place and the product needed has been formed.
TLC 1
TLC 2 (compared with another group (left))
TLC 3
TLC 4
TLC 5

3. Materials and Methods
Step 1
First step was to oxidize the methyl group on the nitrotoluene using sodium dichromate, concentrated sulphuric acid, sodium hydroxide, and water to form a carboxylic acid as the first intermediate (Nitrobenzoic acid)
Scheme 1. Forward reaction of nitrotoluene forming nitrobenzoic acid
Scheme 2. Retrosynthesis of step 1

4. Step 2
Scheme 3. Forward reaction of step 2, the synthesis of Ethyl-4-nitrobenzoate from nitrobenzoic acid
The second step was a Fischer esterification on the carboxylic acid group para to the nitro group on the benzene using excess ethanol and sulphuric acid as the catalyst, to form the ester (Ethyl-4-nitrobenzoate) under reflux.
Scheme 4. Retrosynthesis of step 2

5. Step 3
For the final step, forming benzocaine from Ethyl-4- nitrobenzoate, the nitro group on the para position to the ester on the benzene was reduced to an amino group
Scheme 5. Reaction of Ethyl-4-nitrobenzoate forming the final product Ethyl-4-aminobenzoate (Benzocaine)
Scheme 6. Retrosynthesis of the final step (step 3) in the retrosynthetic route of Benzocaine

6. Analog 1
By using the same method as step 2 and using some left over nitrobenzoic acid the first analog was produced.
Instead of excess ethanol to form the ethyl group on the ester, excess methanol was used forming a methyl group instead
Scheme 7. Reaction of nitrobenzoic acid forming Methyl-4-nitrobenzoate as the first analog. The difference in product from Ethyl-4-nitrobenzoate shown by the red circle.

7. Analog 2
Collecting the first analog product, the second analog can be produced by using the same steps from step 3.
Simply by reducing the nitro group to an amino group keeping the methyl group on the ester, the product formed is Methyl-4-aminobenzoate instead of Ethyl-4-aminobenzoate
Scheme 8. Reaction of Methyl-4-nitrobenzoate forming the second analog, Methyl-4-aminobenzoate, the similarity in the product compared with Benzocaine and difference in the reactant shown by the blue circle.

8. The formation of Benzocaine from Ethyl-4-nitrobenzoate
Discussion of TLC plates from steps 2 to 3:
The formation of Benzocaine from Ethyl-4-nitrobenzoate
Looking at TLC plate number 3 and 4 the starting material (Ethyl-4-nitrobenzoate) spots correlate with the pure sample in TLC 3 and shows no spots in TLC 4 compared to the sample product and pure product of Benzocaine, therefore all sample material had successfully reacted.
TLC 3
TLC 4

9. More discussion of the results from step 2 to step 3:
Spectra 1. IR of Ethyl-4-nitrobenzoate
Spectra 2. IR of Ethyl-4-aminobenzoate (Benzocaine)
Excluding the fingerprint region, when looking at IR spectra of Ethyl-4-nitrobenzoate compared to Ethyl-4-aminobenzoate (benzocaine) the main differences seen can be within the 2 red circles at around a wavenumber of cm -1 and cm-1 due to changing the nitro group for an amino group.

10. Comparison of results with another group on step 2:
When comparing results on TLC 2 with another group of chemistry students, the main spots that showed on the TLC plate were in the same place along with the sample used before placing it on reflux for an hour and a half, shown by the blue circles.
However, there are some more spots present on the left TLC plate (the other groups work), shown by the red circle, most likely due to being left in the TLC solvent for too long and letting the solvent run up the plate for too long, which can start to be seen in our plate on the right by the little red circle, but it was removed before any more spots could develop.
TLC plate 2. Another groups result (Left) showing sample on the left and product on the right, compared to our result (Right) showing the sample on the right and product on the left before and after reflux.

11. Results and discussion of Analog 1 and Analog 2:
Spectra 3. IR of Analog 1 (methyl-4-nitrobenzoate)
Spectra 4. IR of Analog 2 (methyl-4-aminobenzoate)
Whilst excluding the fingerprint region, the main difference (shown by the red circles) shown in the region with a wavenumber of around cm-1 is due to the change from the nitro group to an amino group on the benzene ring para to the ester.

12. Conclusions
Another thing to keep in mind when trying to purify crude products using rotary evaporators to slowly turn the pressure down when enough solvent is evaporating and condensing off due to the possibility that all the sample will shoot up the condenser if the pressure was too low.
TLC plate 2
A few things to take away from doing these experiments are mostly to do with carrying out the methods found by adjusting them when needed. For example, when putting samples on to reflux its best to keep checking by spotting TLC plates, making sure all the sample has reacted forming the product desired instead of just following the method found online, but also making sure to not let the solvent run up the plate too long. An example of this can be seen on TLC plate 2 on the left.

13. Thank you for listening,
Any Questions?