Synthesis of paracetamol (acetaminophen) from biomass-derived p-hydroxybenzamide

Patent metadata

Field	Value
Publication number	US-10286504-B2
Application number	US-201815914597-A
Country	US
Kind code	B2
Filing date	Mar 7, 2018
Priority date	Mar 8, 2017
Publication date	May 14, 2019
Grant date	May 14, 2019

Abstract

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.

First claim

What is claimed is:

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.

Assignees

• Wisconsin Alumni Res Found

Inventors

• Ralph John
• Karlen Steven
• Mobley Justin

Classifications

• B60L53/66

  Data transfer between charging stations and vehicles · CPC title

• H01M16/006

  of fuel cells with rechargeable batteries · CPC title

• H01M2250/20

  Fuel cells in motive systems, e.g. vehicle, ship, plane · CPC title

• H01M8/04925

  Power, energy, capacity or load · CPC title

• C07C231/10

  from compounds not provided for in groups C07C231/02 - C07C231/08 · CPC title