AN EFFICIENT NEW PROCESS FOR SYNTHESIS OF 2-AMINO-5-CHLORO-N-,3-DIMETHYLBENZAMIDE
Described herein are novel methods of synthesizing 2-amino-5-chloro-N,3-dimethylbenzamide. Compounds prepared by the methods disclosed herein are useful for preparation of certain anthranilamide compounds that are of interest as insecticides, such as, for example, the insecticides chlorantraniliprole and cyantraniliprole.
1 . A method of preparing a compound of Formula IV,
wherein each of R 7 -R 10 is independently selected from hydrogen, halogen, halogenated C 1 -C 5 alkyl, and C 1 -C 5 alkyl; and
wherein at least one of R 7 -R 10 is a halogen,
the method comprising:
I) forming a first mixture comprising
A) a compound of Formula IL,
wherein each of R 1 -R 5 is independently selected from hydrogen, halogen, and C 1 -C 5 alkyl; and
B) an acid;
II) reacting the first mixture;
III) introducing a halogenation reagent to the first mixture to form a second mixture; and
IV) reacting the second mixture.
2 . The method of claim 1 , wherein the acid is selected from sulfuric acid, acetic acid, and combinations thereof.
3 . The method of claim 1 , wherein the halogenation reagent is selected from a chlorination reagent, a bromination reagent, an iodination reagent, and combinations thereof.
4 . The method of claim 3 , wherein the chlorination reagent is selected from chlorine, thionyl chloride, phosgene, diphosgene, triphosgene, oxalyl chloride, sulfuryl chloride, phosphorus trichloride, phosphorus oxychloride, trichloroisocyanuric acid, and combinations thereof.
5 . The method of claim 1 , wherein the compound of Formula IV has the following structure
and the compound of Formula II has the following structure
6 . A method of preparing a compound of Formula V,
wherein each of R 7 -R 10 is independently selected from hydrogen, halogen, halogenated C 1 -C 5 alkyl, and C 1 -C 5 alkyl; and
wherein at least one of R 7 -R 10 is a halogen, the method comprising:
I) forming a mixture comprising:
A) a compound of Formula IV,
wherein each of R 7 -R 10 is independently selected from hydrogen, halogen, halogenated C 1 -C 5 alkyl, and C 1 -C 5 alkyl; and
wherein at least one of R 7 -R 10 is a halogen;
B) an oxidation agent;
C) a solvent; and
D) a catalyst; and
II) reacting the mixture.
7 . The method of claim 6 , wherein the compound of Formula V has the following structure
and the compound of Formula IV has the following structure
8 . The method of claim 6 , wherein the oxidation agent is selected from oxygen, chlorine, sodium hypochlorite, chromium trioxide, 3-chloroperoxybenzoic acid, hydrogen peroxide, peroxyacetic acid, potassium peroxymonosulfate, potassium permanganate, and combinations thereof, preferably wherein the oxidation agent is hydrogen peroxide.
9 . The method of claim 6 , wherein the solvent is selected from acetonitrile, methanol, ethanol, isopropanol, water, dimethylformamide, dimethyl sulfoxide, N-Methylpyrrolidone, tetrahydrofuran, acetic acid, acetic anhydride, propionic acid, butyric acid, and combinations thereof.
10 . The method of claim 6 , wherein the catalyst is selected from sulfuric acid, hydrogen chloride, nitric acid, and combinations thereof.
11 . A method of preparing a compound of Formula V,
wherein each of R 7 -R 10 is independently selected from hydrogen, halogen, halogenated C 1 -C 5 alkyl, and C 1 -C 5 alkyl; and
wherein at least one of R 7 -R 10 is a halogen,
the method comprising reacting a compound of Formula III with a halogenation reagent in a solvent, followed by adding an oxidation agent to the solution in the presence of a catalyst, wherein the compound of Formula III has the structure:
wherein each of R 1 -R 4 is independently selected from hydrogen, halogen, and C 1 -C 5 alkyl.
12 . The method of claim 11 for preparing a compound of Formula V, the method comprising:
I) forming a first mixture comprising:
A) the compound of Formula III;
B) the solvent; and
C) the halogenation reagent;
II) reacting the first mixture;
III) introducing a second mixture to the first mixture to form a third mixture, the second mixture comprising
D) the oxidation agent; and
E) the catalyst; and
IV) reacting the third mixture.
13 . A method of preparing a compound of Formula IV,
wherein each of R 7 -R 10 is independently selected from hydrogen, halogen, halogenated C 1 -C 5 alkyl, and C 1 -C 5 alkyl;
wherein at least one of R 7 -R 10 is a halogen, the method comprising:
I) forming a mixture comprising:
A) a compound of Formula III,
wherein each of R 1 -R 4 is independently selected from hydrogen, halogen, and C 1 -C 5 alkyl;
B) a solvent;
C) a halogenation reagent; and
II) reacting the mixture.
14 . The method of claim 13 , wherein the compound of Formula IV has the following structure
and wherein the compound of Formula III has the following structure
15 . The method of claim 13 , wherein the solvent is selected from acetonitrile, dichloroethane, toluene, chlorobenzene, xylene, acetic acid, acetic anhydride, propionic acid, butyric acid, and combinations thereof, and/or
wherein the halogenation reagent is selected from a chlorination reagent, a bromination reagent, an iodination reagent, and combinations thereof, and/or
wherein the method step II) of reacting the mixture occurs at a reaction temperature in the range of about 20° C. to about 140° C.
16 . The method of claim 15 , wherein the method step II) of reacting the mixture occurs at a reaction temperature in the range of about 120° C. to about 130° C.