Process for preparing 3,4-dichloro-n-(2-cyanophenyl)-5-isothiazolecarboxamide

Patent metadata

Field	Value
Publication number	US-11220487-B2
Application number	US-201816619925-A
Country	US
Kind code	B2
Filing date	Jun 11, 2018
Priority date	Jun 14, 2017
Publication date	Jan 11, 2022
Grant date	Jan 11, 2022

Abstract

The present invention relates to a novel process for preparing and isolating 3,4-dichloro-N-(2-cyanophenyl)-5-isothiazolecarboxamide (Isotianil), which can be used as an active compound with microbicidal properties, wherein the amount of waste materials—e.g. solvents and diluents—is significantly reduced and the process meets the requirements of industrial scale production, in particular that it provides the product in high yield, high purity, i.e. minimum amount of by-products and impurities, and can be carried out with tolerable corrosivity in industrial scale metal, in particular stainless steel, vessels or Cr—Ni—Mo alloy pressure filters or centrifuges.

First claim

The invention claimed is:

1. A process for preparing 3,4-dichloro-N-(2-cyanophenyl)-5-isothiazolecarboxamide of formula (I)

by
(a) reacting in an organic solvent selected from the group consisting of toluene, o-xylene, m-xylene, and p-xylene, 3,4-dichloroisothiazole-5-carbonyl chloride of formula (II)

with anthranilamide of formula (III)

and
(b) subsequently dehydrating N-[2-(aminocarbonyl)phenyl]-3,4-dichloro-5-isothiazolecarboxamide of formula (IV)

with a dehydrating agent, wherein (b) is carried out without isolation of N-[2-(aminocarbonyl)phenyl]-3,4-dichloro-5-isothiazolecarboxamide of formula (IV),

wherein the workup comprises
(c) aqueous work-up with an inorganic base (quenching),
(d) degassing of the quenched reaction mixture,
(e) adjustment of pH of the reaction mixture, and
(f) filtration and isolation of the product,
wherein an acid acceptor is not present in (a).

2. The process according to claim 1 , wherein (a) and (b) are carried out in toluene.

3. The process according to claim 1 , wherein (a) is carried out at a temperature in the range between 20° C. to 160° C.

4. The process according to claim 1 , wherein (a) is carried out at a temperature in a range from the boiling point of the respective solvent used in the process to 10K above said boiling point.

5. The process according to claim 1 , wherein a reagent used as dehydrating agent in (b) is selected from the group consisting of mixtures of dialkylformamide with thionyl chloride, phosphorus oxychloride, phosgene and/or chloromethylenedimethylammonium chloride.

6. The process according to claim 5 , wherein the amounts of phosgene or thionyl chloride employed in (b) are between 1 and 2.5 mol per mole of 3,4-dichloroisothiazole-5-carbonyl chloride.

7. The process according to claim 5 , wherein the amounts of dialkylformamide employed in (b) are between 1.0 and 8.0 mol per mole of 3,4-dichloroisothiazole-5-carbonyl chloride.

8. The process according to claim 1 , wherein the base used in the workup of (c) is selected from the group consisting of carbonate or hydroxides of alkali or earth alkali metals.

9. The process according to claim 1 , wherein in (c) the pH is adjusted to a pH between 1.0 and 6.0.

10. The process according to claim 1 , wherein the mixture after addition of the base in (c) is heated to 50° C. 60° C., and stirred at that temperature over a period of 2.0 to 4.0 h for degassing.

11. The process according to claim 1 , wherein the pH after degassing is adjusted to a pH between 5 and 7.

12. The process according to claim 1 , wherein (a) is carried out under reduced pressure and the temperature is in a range from the boiling point under said pressure of the respective solvent used in the process to 10K above said boiling point.

13. The process according to claim 12 , wherein (a) is carried out under reduced pressure, wherein the pressure is in a range from 10 mbar to 700 mbar.

14. A process for preparing 3,4-dichloro-N-(2-cyanophenyl)-5-isothiazolecarboxamide of formula (I)

by
(a) reacting in an organic aromatic solvent 3,4-dichloroisothiazole-5-carbonyl chloride of formula (II)

with anthranilamide of formula (III)

to produce N-[2-(aminocarbonyl)phenyl]-3,4-dichloro-5-isothiazole-carboxamide of formula (IV),

(b) subsequently dehydrating N-[2-(aminocarbonyl)phenyl]-3,4-dichloro-5-isothiazole-carboxamide of formula (IV),
wherein (b) is carried out without isolation of N-[2-(aminocarbonyl)phenyl]-3,4-dichloro-5-isothiazolecarboxamide of formula (IV)
(c) aqueous work-up with an inorganic base (quenching), with optional adjustment of pH,
(d) degassing of quenched reaction mixture,
(e) adjustment of pH of the reaction mixture, and
(f) filtration and isolation of the product,
wherein the organic aromatic solvent is selected from the group consisting of benzene, toluene, o-xylene, m-xylene and p-xylene, and,
(a) is carried out in a range of 105-115° C., and
(b) is carried out in the presence of a dehydrating agent in a range of 16° C. to 30° C.,
wherein the dehydrating agent is a mixture of dimethylformamide and thionylchloride,
wherein the amount of thionyl chloride is between 1.0 and 1.5 mol per mole of 3,4-dichloroisothiazole-5-carbonyl chloride, and
wherein the amount of dimethylformamide is between 4.0 and 5.0 mol per mole of 3,4-dichloroisothiazole-5 carbonyl chloride, and
wherein (c) comprises addition of a 32% solution of sodium hydroxide, wherein the amount of sodium hydroxide is between 1.8 and 2.2 mol per mole of thionyl chloride, wherein the pH after quenching is between 1.8 and 2.2,
wherein the reaction mixture is added to the base over a period of time of 2 hours under temperature control, wherein the temperature is allowed to increase to a range from 50° C. to 60° C., and
wherein in (d) volatile reaction products are removed from the reaction mixture by degassing over a period of 2 to 4 h at 55° C., and
wherein in (e), the temperature is adjusted to 20° C. to 22° C. and then the pH is adjusted to a pH in the range between 5 and 6 with a 32% solution of sodium hydroxide, and wherein the precipitated product is filtered off and washed with water and methanol.

15. The process according to claim 5 , wherein the amounts of phosgene or thionyl chloride employed in (b) are between 1 and 1.3 mol per mole of 3,4-dichloroisothiazole-5-carbonyl chloride.

16. The process according to claim 5 , wherein the amounts of dialkylformamide employed in (b) are between 4.3 and 4.7 mol per mole of 3,4-dichloroisothiazole-5 carbonyl chloride.

17. The process according to claim 1 , wherein the base used in the workup of (c) is selected from the group consisting of sodium carbonate, potassium carbonate, sodium hydroxide, and potassium hydroxide.

18. The process according to claim 1 , wherein in (c) the pH is adjusted to a pH between 1.8 and 2.2.

19. The process according to claim 1 , wherein the mixture after addition of the base in (c) is heated to 50° C.-60° C. and stirred at that temperature over a period of 1.0 h to 2.5 h-for degassing.

20. The process according to claim 12 , wherein the process (a) is carried out under reduced pressure, wherein the pressure is in a range from 200 mbar to 400 mbar.

Assignees

• Bayer Ag

Inventors

• Farida Taraneh
• Littmann Martin
• Hartmann Daniel
• Pabst Kyra Larissa
• Sanli Ali

Classifications

• C07D275/03 Primary

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title

• C07B43/08

  of cyano groups · CPC title

• A01N43/80

  five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2 · CPC title