Synthesis of paracetamol (acetaminophen) from biomass-derived p-hydroxybenzamide
Disclosed is a method to make N-acetyl-p-aminophenol. The method includes steps for converting biomass-derived p-hydroxybenzoates to p-hydroxybenzamide, then to p-aminophenol; and then N-acetylating the p-aminophenol.
1. A method to make N-acetyl-p-aminophenol, the method comprising:
(a) converting p-hydroxybenzamide to p-aminophenol; and then
(b) N-acetylating at least a portion of the p-aminophenol to yield N-acetyl-p-aminophenol.
2. The method of claim 1 , wherein, step (a) comprises contacting the p-hydroxybenzamide with a hypohalite salt to cause a Hofmann-style rearrangement reaction, thereby yielding p-aminophenol.
3. The method of claim 1 , wherein step (b) comprises contacting the p-aminophenol with acetic anhydride and water for a time and at a temperature to yield N-acetyl-p-aminophenol.
4. The method of claim 1 , wherein, step (a) comprises contacting the p-hydroxybenzamide with a hypohalite salt to cause a Hofmann-style rearrangement reaction, thereby yielding p-aminophenol; and
step (b) comprises contacting the p-aminophenol with acetic anhydride and water for a time and at a temperature to yield N-acetyl-p-aminophenol.
5. The method of claim 4 , wherein step (a) is conducted in an alkaline aqueous or non-aqueous solvent, at a pH from about 10 to about 14, a temperature from about 20° C. to about 100° C., and for a time of from about 30 minutes to about 24 h.
6. The method of claim 4 , wherein step (b) is conducted at a temperature of from about 100° C. to about 150° C.
7. The method of claim 4 , wherein step (a) is conducted in an alkaline aqueous or non-aqueous solvent, at a pH from about 10 to about 14, a temperature from about 20° C. to about 100° C., and for a time of from about 30 minutes to about 24 h; and
step (b) is conducted at a temperature of from about 100° C. to about 150° C.
8. A method to make N-acetyl-p-aminophenol, the method comprising:
(a) providing p-hydroxybenzamide derived from p-hydroxybenzoate esters derived from biomass;
(b) converting at least a portion of the p-hydroxybenzamide to p-aminophenol; and then
(c) N-acetylating at least a portion of the p-aminophenol to yield N-acetyl-p-aminophenol.
9. The method of claim 8 , wherein, step (b) comprises contacting the p-hydroxybenzamide with a hypohalite salt to cause a Hofmann-style rearrangement reaction, thereby yielding p-aminophenol.
10. The method of claim 8 , wherein step (c) comprises contacting the p-aminophenol with acetic anhydride and water for a time and at a temperature to yield N-acetyl-p-aminophenol.
11. The method of claim 8 , wherein, step (b) comprises contacting the p-hydroxybenzamide with a hypohalite salt to cause a Hofmann-style rearrangement reaction, thereby yielding p-aminophenol; and
step (c) comprises contacting the p-aminophenol with acetic anhydride and water for a time and at a temperature to yield N-acetyl-p-aminophenol.
12. The method of claim 11 , wherein step (b) is conducted in an alkaline aqueous or non-aqueous solvent, at a pH from about 10 to about 14, a temperature from about 20° C. to about 100° C., and for a time of from about 30 minutes to about 24 h.
13. The method of claim 11 , wherein step (c) is conducted at a temperature of from about 100° C. to about 150° C.
14. The method of claim 11 , wherein step (b) is conducted in an alkaline aqueous or non-aqueous solvent, at a pH from about 10 to about 14, a temperature from about 20° C. to about 100° C., and for a time of from about 30 minutes to about 24 h; and
step (c) is conducted at a temperature of from about 100° C. to about 150° C.
15. A method to make N-acetyl-p-aminophenol from lignin, the method comprising:
(a) performing an ammonia fiber expansion process reaction or an extractive ammonia process reaction on lignin to yield p-hydroxybenzamide;
(b) converting at least a portion of the p-hydroxybenzamide from step (a) to p-aminophenol; and then
(c) N-acetylating at least a portion of the p-aminophenol from step (b) to yield N-acetyl-p-aminophenol.
16. The method of claim 15 , wherein, step (b) comprises contacting the p-hydroxybenzamide with a hypohalite salt to cause a Hofmann-style rearrangement reaction, thereby yielding p-aminophenol.
17. The method of claim 15 , wherein step (c) comprises contacting the p-aminophenol with acetic anhydride and water for a time and at a temperature to yield N-acetyl-p-aminophenol.
18. The method of claim 15 , wherein, step (b) comprises contacting the p-hydroxybenzamide with a hypohalite salt to cause a Hofmann-style rearrangement reaction, thereby yielding p-aminophenol; and
step (c) comprises contacting the p-aminophenol with acetic anhydride and water for a time and at a temperature to yield N-acetyl-p-aminophenol.
19. The method of claim 18 , wherein step (b) is conducted in an alkaline aqueous or non-aqueous solvent, at a pH from about 10 to about 14, a temperature from about 20° C. to about 100° C., and for a time of from about 30 minutes to about 24 h.
20. The method of claim 18 , wherein step (c) is conducted at a temperature of from about 100° C. to about 150° C.
21. The method of claim 18 , wherein step (b) is conducted in an alkaline aqueous or non-aqueous solvent, at a pH from about 10 to about 14, a temperature from about 20° C. to about 100° C., and for a time of from about 30 minutes to about 24 h; and
step (c) is conducted at a temperature of from about 100° C. to about 150° C.