Processes for the preparation of pesticidal compounds
View Patent ↗This application relates to efficient and economical synthetic chemical processes for the preparation of pesticidal thioethers and pesticidal sulfoxides. Further, the present application relates to certain novel compounds necessary for their synthesis. It would be advantageous to produce pesticidal thioethers and pesticidal sulfoxides efficiently and in high yield from commercially available starting materials.
1. A process for preparing a compound of the formula 1
wherein each of R 1 and R 2 is independently selected from the group consisting of H, F, Cl, Br, I, C 1 -C 6 alkyl and trifluoromethyl, R 3 is H or C 1 -C 6 alkyl, and R 4 is H or —C(O)C 1 -C 6 alkyl; comprising
a. contacting a compound of the formula
wherein each of R 1 and R 2 is independently selected from the group consisting of H, F, Cl, Br, I, C 1 -C 6 alkyl and trifluoromethyl, R 3 is H or C 1 -C 6 alkyl, and R 4 is H or —C(O)C 1 -C 6 alkyl; with a 3-halopyridine in the presence of a copper catalyst, a ligand, a base, a solvent and an additive.
2. The process of claim 1 , wherein the copper catalyst in step (a) is copper (I) chloride (CuCl ), copper (II) chloride (CuCl 2 ), copper (I) bromide (CuBr) or copper (I) iodide (CuI ).
3. The process of claim 1 , wherein the ligand in step (a) is selected from the group consisting of triethylenetetramine (TETA), N,N′-bis(2-hydroxyethyl)ethylenediamine (BHEEA) and 8-hydroxyquinoline.
4. The process of claim 1 , wherein the additive is used, and the additive is a dialkylamine, a trialkylamine, a benzonitrile or N,N,N′N′-tetramethylethylenedinamine (TMEDA).
5. The process of claim 1 , wherein the ligand in step (a) is N,N′-dimethylethane-1,2-diamine (DMEDA), and the additive is used and the additive is a dialkylamine, a trialkylamine, a benzonitrile or N,N,N′N′-tetramethylethylenedinamine (TMEDA).
6. The process of claim 1 , wherein the base in step (a) is selected from the group consisting of sodium bicarbonate (NaHCO 3 ), sodium carbonate (Na 2 CO 3 ), calcium carbonate (CaCO 3 ), cesium carbonate (Cs 2 CO 3 ), lithium carbonate (Li 2 CO 3 ), potassium carbonate (K 2 CO 3 ), lithium hydroxide (LiOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), cesium hydroxide (CsOH), calcium hydroxide (Ca(OH) 2 ), sodium diphosphate (Na 2 HPO 4 ), potassium phosphate (K 3 PO 4 ), sodium phosphate (Na 3 PO 4 ), sodium methoxide (NaOCH 3 ) and sodium ethoxide (NaOCH 2 CH 3 ).
7. The process of claim 1 , wherein the solvent of step (a) is acetonitrile (CH 3 CN), benzonitrile, dioxane, N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP), tetrahydrofuran (THF), dimethylsulfoxide (DMSO), 2-methyl tetrahydrofuran, toluene, methanol (MeOH), or ethanol (EtOH).
8. The process of claim 1 , wherein the 3-halopyridine is 3-bromopyridine.
9. The process of claim 1 , wherein R 3 is H.
10. The process of claim 1 , wherein R 1 is Cl.
11. A process for preparing a compound of the formula
comprising
a. contacting a compound of the formula 1b
with a 3-halopyridine in the presence of a copper catalyst, a ligand, a base and an additive to provide a compound of the formula 1c
b. contacting a compound of the formula 1c
with an alkylating agent in the presence of a base to provide a compound of the formula 1c′
; and
c. contacting a compound of the formula 1c′
with an inorganic acid to provide compound 1d.
12. The process of claim 11 , wherein the copper catalyst in step (a) is copper (I) chloride (CuCl), copper (II) chloride (CuCl 2 ), copper (I) bromide (CuBr) or copper (I) iodide (CuI).
13. The process of claim 11 , wherein the ligand in step (a) is selected from the group consisting of triethylenetetramine (TETA), N,N′-bis(2-hydroxyethyl)ethylenediamine (BHEEA) and 8-hydroxyquinoline.
14. The process of claim 11 , wherein the additive is used in step (a), and the additive is a dialkylamine, a trialkylamine, a benzonitrile or N,N,N′N′-tetramethylethylenedinamine (TMEDA).
15. The process of claim 11 , wherein the ligand in step (a) is N,N′-dimethylethane-1,2-diamine (DMEDA), and the additive is used and the additive is a dialkylamine, a trialkylamine, a benzonitrile or N,N,N′N′-tetramethylethylenedinamine (TMEDA).
16. The process of claim 11 , wherein the base in step (a) is selected from the group consisting of sodium bicarbonate (NaHCO 3 ), sodium carbonate (Na 2 CO 3 ), calcium carbonate (CaCO 3 ), cesium carbonate (Cs 2 CO 3 ), lithium carbonate (Li 2 CO 3 ), potassium carbonate (K 2 CO 3 ), lithium hydroxide (LiOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), cesium hydroxide (CsOH), calcium hydroxide (Ca(OH) 2 ), sodium diphosphate (Na 2 HPO 4 ), potassium phosphate (K 3 PO 4 ), sodium phosphate (Na 3 PO 4 ), sodium methoxide (NaOCH 3 ) and sodium ethoxide (NaOCH 2 CH 3 ).
17. The process of claim 11 , wherein the solvent of step (a) is acetonitrile (CH 3 CN), benzonitrile, dioxane, N, N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP), tetrahydrofuran (THF), 2-methyl tetrahydrofuran, dimethylsulfoxide (DMSO), toluene, methanol (MeOH), or ethanol (EtOH).
18. The process of claim 11 , wherein the alkylating agent in step (b) is a C 1 -C 6 alkyl group substituted with a leaving group selected from the group consisting of Br, I, a triflate (-OTf), a tosylate (-OTs) and a mesylate (-OMs).
19. The process of claim 11 , wherein the base in step (b) is selected from the group consisting of sodium bicarbonate (NaHCO 3 ), sodium carbonate (NaHCO 3 ), calcium carbonate (CaCO 3 ), cesium carbonate (Cs 2 CO 3 ), lithium carbonate (Li 2 CO 3 ), potassium carbonate (K 2 CO 3 ), lithium hydroxide (LiOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), cesium hydroxide (CsOH), calcium hydroxide (Ca(OH) 2 ), sodium hydride (NaH), lithium hydride (LiH), potassium hydride (KH), sodium methoxide (NaOCH 3 ), sodium ethoxide (NaOCH 2 CH 3 ) and sodium t-butoxide (NaOt-Bu).
20. The process of claim 11 , wherein the inorganic acid in step (c) is selected from the group consisting of HF, HCl, HBr, H 2 SO 4 , H 3 PO 4 , H 3 BO 4 , HNO 3 and HClO 4 .