Piperine is a yellow crystalline compound that is slightly soluble in water but more soluble in alcohol. It forms salts with strong acids and has properties of melting point between 128 to 130 °C. Piperine is used as a food spice and flavoring agent that can increase nutrient absorption and improve attention and reasoning skills. The six step synthesis of piperine was developed in 1894 and involves the Reimer-Tiemann reaction, Claisen-Schmidt reaction, Perkin reaction, and acid-catalyzed reactions to convert protocatechuic acid to piperine.

1. Synthesis of Piperine
D. Jim Livingston,
Asst. Prof. of Chemistry,
St. John’s College.

2. PIPERINE
 Properties:
 yellow crystalline compound having melting
point 128 to 130 °C
 slightly soluble in water but more soluble in alcohol
 Forms salts with strong acids.
 Uses:
 Food spice and flavoring agent
 increase the level of absorption of nutrients within
our body
 improving our attention and reasoning skills

3. Synthesis
 Ladenberg 1894.
 Involves six steps.
 Catechol Piperine

4. Step 1

5. Reimer Tiemann Reaction

7. Step 1
Protocatechuic acid

8. Step 2

9. Mechanism
SN2 Reaction
Proton abstraction Nucleophilic attack – Sub. product
Proton abstraction – intramolecular nucleophilic substitution

10. Step 2
Piperonal

11. Step 3

12. Claisen-Schmidt Reaction

13. Step 3

14. Step 4

15. Perkin Reaction

19. Cinnamic acid
+ CH3COOH

20. Step 4
Piperic acid

21. Step 5 and Step 6
-HCl
Piperoylchloride
Piperine

23. References:
https://chemistry.stackexchange.com/questions/86765/reimer-
tiemann-like-reaction-of-catechol-with-diiodomethane
https://www.synarchive.com/named-reactions/claisen-schmidt-
condensation