synthesis of p-aminobenzoic acid - step i

1. Synthesis of p-aminobenzoic acid - Step I

2. Aim You are going to do an acylation on p-toluidine. Characterization of the product by melting point and 1H NMR spectroscopy.

3. Introduction

4. Introduction Amines are pharmaceutical agents.

5. Introduction

6. Introduction Aminobenzoic acids and their derivatives are important for the preparation of: 1. Dyes 2. Flavors 3. Preservatives.

7. Introduction p-Aminobenzoic acid or 4-aminobenzoic acid is a constituent part of folic acid (Vitamin B10).

8. Introduction It is necessary for the growth, the feather development and the blood structure. It also influences breeding results. A shortage may lead to discolouration and a growth slowdown. 

9. Introduction It is used as an UV-blocking ingredient in sun tan cosmetics. It is used in medical field for preparing local anesthetic and ointments.

10. Introduction Acylation of amines is put to a practical use. The following two compounds are obtained from acylation of an amine. 1. N, N-diethyl-m-toluamide is an INSECT REPPELLENT OFF. 2. Acetanilide is an ANTIPYRECTIC i.e. FEVER REDUCING AGENT.

11. Synthesis Many methods are available to make aminobenzoicacids.

12. Synthesis Synthesis of p-aminobenzoic acid from p-toluidine is a three step reaction. 1. Acylation on Amino group. 2. Oxidation on Methyl group. 3. Hydrolysis of acetyl group.

13. Synthesis

14. Synthesis Amines are nitrogen nucleophiles. They readily react with the carbonyl group of acid derivatives: 1. Acyl chlorides 2. Acid anhydrides. 3. Acid Esters. They undergo nucleophilic acyl substitution reaction.

15. Synthesis Today we will do the acylation on amino group i.e. protecting –NH2 group in p-toluidine. Why do we have to protect the amino group????? 1.Amide is much less susceptible to oxidation by permanganate than the original amine.

16. Mechanism

17. Mechanism

18. Procedure Weigh 7.5 g of p-toluidine in a 250 mL Erlenmeyer flask. Add 175 mL of water and 6.5 mL of conc. HCl. Swirl the flask gently for through mix.

19. Procedure If the solution is discolored, add two gram of activated charcoal. Why??? To remove the color from the reaction mixture. Stir for several minutes and filter the solution using Buchner funnel (make the filter paper wet before doing the filtration).

20. Procedure Make a solution of 12 gram of sodium acetate in 22 mL of water This solution has to be clear and if you find any undissolved sodium acetate particles then filter the solution.

21. Procedure Add 8 mL of acetic anhydride to the p-toluidine solution and swirl the flask. Add the sodium acetate solution in one lot and mix the solution thoroughly. Cool the reaction mixture in an ice bath with rapid and continuous stirring.

22. Procedure You will see nice crystals or precipitate in the flask. Filter the crystals using Buchner funnel. Wash it with cold water twice (may be 10 mL each time) Allow them to dry on its own using vacuum.

23. Characterization Find its melting point. Record its IR spectrum. Record its 1H NMR spectrum.

24. Notes Acetic anhydride gives strong acetic acid smell, so pleas do not remove them from the hood. Concentrated hydrochloric acid’s fumes are dangerous, so use it under the hood. Record the IR spectrum and find the melting point for p-toluidine.