Process for preparing alkyl pyroglutamic acids
View Patent ↗This disclosure relates to methods for limiting the undesired reverse Mannich reaction during the hydrogenation reduction of one or more nitro functional groups (—NO 2 ) to their corresponding amines (—NH 2 ).
1. A method of producing a compound of formula (I):
wherein
R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are independently selected from H, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl(C 1 -C 6 alkyl), aryl, aryl(C 1 -C 6 alkyl), heteroaryl, and heteroaryl(C 1 -C 6 alkyl); and
X is selected from C 2 -C 20 alkylene, C 2 -C 20 heteroalkylene, C 2 -C 20 alkenylene, C 2 -C 20 alkynylene, C 3 -C 8 cycloalkyl, aryl, and —Y—Z—Y—;
wherein each Y independently is C 1 -C 10 alkylene, or C 2 -C 10 heteroalkylene, and Z is aryl, heteroaryl, or heterocyclyl;
the method comprising reacting a compound of formula (II):
wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and X are as defined above;
with H 2 in a solvent and in the presence of: a) a catalyst, b) at least about 0.1 molar equivalents of a nitro(C 1 -C 10 alkane) optionally substituted with one or more OH groups, and c) at least about 0.1 molar equivalents of formaldehyde.
2. The method of claim 1 , wherein reacting is in the presence of d) a basic amine.
3. The method of claim 2 , wherein the basic amine is selected from the group consisting of triethylamine, tri(C 1 -C 6 alkyl)amine, tri(hydroxyl C 1 -C 6 alkyl)amine, quinuclidine, morpholine, piperidine, pyridine, imidazole, and alkylimidazole.
4. The method of claim 2 , wherein the basic amine is triethylamine and present in about 0.0005 to about 0.2 molar equivalents.
5. The method of claim 1 , wherein the catalyst is nickel-based or platinum-based.
6. The method of claim 1 , wherein the nitro(C 1 -C 10 alkane) is 2-nitropropane, 2-methyl-2-nitro-1-propanol, or 2-methyl-2-nitro-1,3-propanediol.
7. The method of claim 1 , wherein the nitro(C 1 -C 10 alkane) is 2-nitropropane or 2-methyl-2-nitro-1-propanol.
8. The method of claim 1 , wherein the nitro(C 1 -C 10 alkane) is present in about 0.1 to about 2 molar equivalents.
9. The method of claim 1 , wherein formaldehyde is present in about 0.05 to about 2 molar equivalents.
10. The method of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are independently selected from H and C 1 -C 6 alkyl.
11. The method of claim 1 , wherein R 3 , R 4 , R 5 , and R 6 are independently selected from C 1 -C 6 alkyl.
12. The method of claim 1 , wherein R 1 and R 2 are each H.
13. The method of claim 1 , wherein X is C 2 -C 20 alkylene or C 2 -C 20 heteroalkylene.
14. The method of claim 1 , wherein X is hexylene.
15. The method of claim 1 , wherein X is a polyoxyalkylene moiety having two or more oxyalkyl groups that are the same or different.
16. The method of claim 1 , wherein X is —(CH 2 ) 2 —O—(CH 2 ) 2 —O—(CH 2 ) 2 —.
17. The method of claim 1 , wherein the catalyst is Raney nickel.
18. The method of claim 1 , wherein the reacting is at a temperature between about 30° C. to about 100° C. and a pressure between about 100 psi to about 1500 psi.
19. The method of claim 1 , wherein the compound of formula (I) is:
20. The method of claim 1 , wherein the compound of formula (I) is:
N 1 ,N 1 ′-(2′-(ethane-1,2-diybis(oxyl)bis(ethane-2,1-diyl))bis(2-
methylpropane-1,2-diamine), or
N 1 ,N 1 ′-(hexane-1,6-diyl)bis(2-methylpropane-1,2-diamine).