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CN-122003401-A - Process for preparing 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile

CN122003401ACN 122003401 ACN122003401 ACN 122003401ACN-122003401-A

Abstract

The present disclosure relates to a process for preparing 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile. The process of the present disclosure is carried out under mild reaction conditions. Further, the methods of the present disclosure are simple, cost effective, and environmentally friendly, and provide 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile with relatively higher purity and higher yield.

Inventors

  • S. Tulaka
  • A - Carlisle
  • M. K. Rajendran

Assignees

  • 克罗普诺赛斯(印度)私人有限公司

Dates

Publication Date
20260508
Application Date
20240831
Priority Date
20230929

Claims (19)

  1. 1. A process for preparing 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile (formula I), the process comprising the steps of: a) Treating a compound of formula II with a phosphorus halide in a first fluid medium under agitation at a first predetermined temperature for a first predetermined period of time to obtain a mixture of a compound of formula III and a compound of formula IV; b) Reducing the mixture of the compound of formula III and the compound of formula IV with a reducing agent in a second fluid medium under agitation at a second predetermined temperature for a second predetermined period of time to obtain the compound of formula IV, and C) Chlorinating the compound of formula IV with a chlorinating agent in a third fluid medium under agitation at a third predetermined temperature for a third predetermined period of time to give 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile (formula I) 。
  2. 2. The method of claim 1, wherein the first fluid medium is selected from the group consisting of methylene chloride, chloroform, carbon tetrachloride, toluene, ethyl acetate, xylene, benzene, tetrahydrofuran, 1, 4-dioxane, and combinations thereof.
  3. 3. The method of claim 1, wherein the phosphorus halide is phosphorus trichloride.
  4. 4. The process of claim 1, wherein the molar ratio of the compound of formula II to the phosphorus halide is in the range of 1:1.5 to 1:5.
  5. 5. The method of claim 1, wherein the first predetermined temperature is in a range of 20 ℃ to 50 ℃.
  6. 6. The method of claim 1, wherein the first predetermined period of time is in a range of 5 hours to 24 hours.
  7. 7. The method of claim 1, wherein the second fluid medium is selected from the group consisting of dimethylacetamide, dimethylformamide, sulfolane, dimethylsulfoxide, N-methylpyrrolidine, acetonitrile, and combinations thereof.
  8. 8. The method of claim 1, wherein the reducing agent is selected from the group consisting of sodium metabisulfite, sodium bisulfite, sodium sulfite, potassium bisulfite, potassium metabisulfite, potassium sulfite, potassium dithionite, sodium dithionite, and combinations thereof.
  9. 9. The method of claim 1, wherein the second predetermined temperature is in the range of 60 ℃ to 150 ℃.
  10. 10. The method of claim 1, wherein the second predetermined period of time is in the range of 2 hours to 10 hours.
  11. 11. The method of claim 1, wherein the chlorinating agent is selected from the group consisting of sodium hypochlorite, phosphorus oxychloride, phosphorus pentachloride, sulfur chloride, and sulfur dichloride.
  12. 12. The method of claim 1, wherein the third fluid medium is water.
  13. 13. The process of claim 1, wherein the molar ratio of the compound of formula IV to the chlorinating agent is in the range of 1:1 to 1:15.
  14. 14. The method of claim 1, wherein the third predetermined temperature is in the range of 20 ℃ to 50 ℃.
  15. 15. The method of claim 1, wherein the third predetermined period of time is in a range of 2 hours to 10 hours.
  16. 16. The process according to claim 1, wherein the yield of 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile is in the range of 65% to 80%.
  17. 17. 4-Chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile prepared according to the method of any one of claims 1 to 16.
  18. 18. The 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile according to claim 17, having a purity of greater than 90%.
  19. 19. The 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile according to claim 18, wherein the purity is in the range of 90% to 99%.

Description

Process for preparing 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile Technical Field The present disclosure relates to a process for preparing 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile. Background The background information hereinbelow relates to the present disclosure, but is not necessarily prior art. 4-Chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile is a key intermediate for the synthesis of cyazofamid (Cyazofamid). The structure of 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile is: 。 Cyazofamid is an important bactericide. Cyazofamid has the chemical name of 4-chloro-2-cyano-N, N-dimethyl-5- (4-tolyl) -1H-imidazole-1-sulfonamide. The cyazofamid has the structure that: 。 Typically, 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile was prepared in DMF in the presence of sodium bisulfite, followed by chlorination using N-chlorosuccinimide (NCS). N-chlorosuccinimide (NCS) is expensive and the succinimide by-products formed during the reaction require cumbersome post-treatments to remove such by-products. In addition, the conventional method for preparing 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile has disadvantages such as severe reaction conditions, long reaction time, low yield, necessity of using toxic, expensive or not readily available reagents, impossibility, and operational limitations in the synthesis process. Thus, conventional methods do not provide an effective solution for the synthesis of 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile. It is therefore desirable to provide a process for the preparation of 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile which overcomes the above disadvantages or at least provides a useful alternative. Object of the Invention Some objects of the present disclosure met by at least one embodiment herein are as follows: It is an object of the present disclosure to ameliorate one or more of the problems of the background art, or at least to provide a useful alternative. It is another object of the present disclosure to provide a process for preparing 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile. It is a further object of the present disclosure to provide a process for preparing 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile, which has a relatively higher purity and higher yield. It is a further object of the present disclosure to provide a simple, efficient and cost effective process for the preparation of 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile. It is yet another object of the present disclosure to provide an environmentally friendly and commercially scalable process for preparing 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile. Other objects and advantages of the present disclosure will become more apparent from the following description, which is not intended to limit the scope of the present disclosure. Disclosure of Invention The present disclosure relates to a process for preparing 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile (formula I). The method comprises treating a compound of formula II with a phosphorus halide in a first fluid medium under agitation at a first predetermined temperature for a first predetermined period of time to obtain a mixture of a compound of formula III and a compound of formula IV. Reducing the mixture of the compound of formula III and the compound of formula IV with a reducing agent in a second fluid medium under agitation at a second predetermined temperature for a second predetermined period of time to obtain the compound of formula IV. Chlorinating the compound of formula IV with a chlorinating agent in a third fluid medium under agitation at a third predetermined temperature for a third predetermined period of time to give 4-chloro-5- (4-tolyl) -1H-imidazole-2-carbonitrile (formula I). In an embodiment of the present disclosure, the first fluid medium is selected from the group consisting of dichloromethane, chloroform, carbon tetrachloride, toluene, ethyl acetate, xylene, benzene, tetrahydrofuran, 1, 4-dioxane, and combinations thereof. In an embodiment of the present disclosure, the phosphorus halide is phosphorus trichloride. In embodiments of the present disclosure, the molar ratio of the compound of formula II to the phosphorus halide is in the range of 1:1.5 to 1:5. In an embodiment of the present disclosure, the first predetermined temperature is in the range of 20 ℃ to 50 ℃. In an embodiment of the present disclosure, the first predetermined period of time is in a range of 5 hours to 24 hours. In an embodiment of the present disclosure, the second fluid medium is selected from the group consisting of dimethylacetamide, dimethylformamide, sulfolane, dimethylsulfoxide, N-methylpyrrolidine, acetonitrile, and combinations thereof. In an embodiment of the present disclosure, the reducing agent is selected from the group consisting of sodium metabisulfite, sodium bisulfite, sodium sulfite, potassium bisulfite, potassium metabisulfite, potassium sulfite, potassium