Process to prepare 3-methyl-2-nitrobenzoic acid by air oxidation
View Patent ↗A method for preparing 3-methyl-2-nitrobenzoic acid is disclosed wherein 1,3-dimethyl-2-nitrobenzene is combined with an oxidation catalayst in the presence of an oxygen source and an initiator, provided that less than 99% of the 1,3-dimethyl-2-nitrobenzene is oxidized. A method for preparing compounds of Formula 7 and Formula 11 is also disclosed wherein the method is characterized by using 3-methyl-2-nitrobenzoic acid as prepared by the method disclosed above wherein R 1 is C 1 -C 7 alkyl, C 3 -C 6 cycloalkyl or C 4 -C 7 alkylcycloalkyl.
1. A method for preparing a compound of Formula 7
wherein R 1 is C 1 -C 7 alkyl, C 3 -C 6 cycloalkyl or C 4 -C 7 alkylcycloalkyl;
comprising (A) contacting a compound of Formula 2
with a reducing agent to form a compound of Formula 3
(B) contacting the compound of Formula 3
with R 2 OC(═O)Cl to form a compound of Formula 4
wherein R 2 is C 1 -C 6 alkyl or C 3 -C 6 alkenyl, each optionally substituted with up to 3 halogen and up to 1 phenyl;
(C) contacting the compound of Formula 4
with a chlorinating agent to form a compound of Formula 5
(D) contacting the compound of Formula 5
with a cyclizing agent to form a compound of Formula 6
(E) contacting the compound of Formula 6
with R 1 NH 2 to form the compound of Formula 7;
characterized by using the compound of Formula 2 as prepared by a method comprising, contacting a compound of Formula 1
with an oxidation catalyst in the presence of an oxygen source and an initiator, provided that less than 99% of a compound of Formula 1 is oxidized.
2. The method of claim 1 wherein R 1 is C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl.
3. The method of claim 2 wherein R 1 is methyl, isopropyl, cyclopropyl or t-butyl.
4. The method of claim 3 wherein R 1 is methyl or t-butyl.
5. The method of claim 1 wherein R 2 is C 1 -C 4 alkyl.
6. The method of claim 5 wherein R 2 is methyl or ethyl.
7. The method of claim 6 wherein R 2 is ethyl.
8. The method of claim 1 wherein the cyclizing agent is PBr 3 .
9. The method of claim 1 wherein the chlorinating agent is HCl and H 2 O 2 .
10. A method for preparing a compound of Formula 11
wherein R 1 is C 1 -C 7 alkyl, C 3 -C 6 cycloalkyl or C 4 -C 7 alkylcycloalkyl;
comprising (A) contacting a compound of Formula 2
with an activating agent and R 1 NH 2 to form a compound of Formula 8;
(B) contacting the compound of Formula 8
with a reducing agent to form a compound of Formula 9
(C) contacting the compound of Formula 9
with a brominating agent to form a compound of Formula 10
(D) contacting the compound of Formula 10
with a cyanating agent to form the compound of Formula 11;
characterized by using the compound of Formula 2 as prepared by a method comprising, contacting a compound of Formula 1
with an oxidation catalyst in the presence of an oxygen source and an initiator, provided that less than 99% of a compound of Formula 1 is oxidized.
11. The method of claim 10 wherein R 1 is C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl.
12. The method of claim 11 wherein R 1 is methyl, isopropyl, cyclopropyl or t-butyl.
13. The method of claim 12 wherein R 1 is methyl or t-butyl.
14. The method of claim 13 wherein R 1 is methyl.
15. The method of claim 14 wherein R 1 is t-butyl.