Methods for forming aryl carbon-nitrogen bond using light

Patent metadata

Field	Value
Publication number	US-11104653-B2
Application number	US-201916404255-A
Country	US
Kind code	B2
Filing date	May 6, 2019
Priority date	May 8, 2018
Publication date	Aug 31, 2021
Grant date	Aug 31, 2021

Abstract

The disclosure relates to a method for forming aryl carbon-nitrogen bonds and to photoreactors useful in these and other light-driven reactions. The method comprises contacting an aryl halide, such as 4-bromobenzotrifluoride, with an amine, such as morpholine, in the presence of a Ni salt catalyst solution and an optional base, thereby forming a reaction mixture; exposing the reaction mixture to light under reaction condition sufficient to produce the aryl carbon-nitrogen bonds, e.g., to give a product such as 4-(4-(trifluoromethyl)phenyl)morpholine. In certain embodiments, the amine may be present in a molar excess to the aryl halide. In certain embodiments, the Ni salt catalyst solution includes a Ni(II) salt and a polar solvent, wherein the Ni(II) salt is dissolved in the polar solvent. In certain embodiments, the reactions conditions include holding the reaction mixture at between about room temperature and about 80° C. for between about 1 hour and about 20 hours such that at least about 50% yield is obtained.

First claim

What is claimed is:

1. A method for forming an aryl carbon-nitrogen bond, the method comprising:
contacting an aryl halide with an amine in the presence of a Ni(II) salt catalyst solution and an optional additional base, thereby forming a reaction mixture; and
exposing the reaction mixture to light under reaction conditions sufficient to form the aryl carbon-nitrogen bond;
wherein the formation of the aryl carbon-nitrogen bond is light-driven and Ni-catalyzed without the addition of a photoredox catalyst under said reaction conditions; wherein the light is at about 300 nm to 405 nm.

2. The method of claim 1 , wherein the reactions conditions comprise holding the reaction mixture under light exposure at between about room temperature and about 80° C. for between about 1 hour and about 20 hours such that at least about 50% reaction yield is obtained.

3. The method of claim 2 , wherein at least about 80% reaction yield is obtained.

4. The method of claim 1 , wherein the aryl halide is selected from the group consisting of an aryl bromide, an aryl chloride, and an aryl iodide.

5. The method of claim 4 , wherein the aryl halide is selected from the group consisting of bromobenzene; 4-bromobenzotrifluoride; 3-bromobenzotrifluoride; 1-bromo-3,5-diflurobenzene; 4-bromobenzofluoride; 1-bromo-3-(trifluoromethyl)benzene; 1-bromo-3-chlorobenzene; 4-bromobenzamide; 1-bromo-4-methylbenzene; 1-bromo-4-methoxybenzene; 1-bromo-3-methoxybenzene; 1-bromo-3,5-dimethoxybenzene; 4-bromobenzonitrile; methyl 4-bromobenzoate; 1-(4-bromophenyl)ethan-1-one; 3-bromopyridine; 5-bromopyrimidine; chlorobenzene; 4-chlorobenzotrifluoride; 3-chlorobenzotrifluoride; 1-chloro-3,5-diflurobenzene; 4-chlorobenzofluoride; 1-chloro-3-(trifluoromethyl)benzene; 1-chloro-3-chlorobenzene; 4-chlorobenzamide; 1-chloro-4-methylbenzene; 1-chloro-4-methoxybenzene; 1-chloro-3-methoxybenzene; 1-chloro-3,5-dimethoxybenzene; 4-chlorobenzonitrile; methyl 4-chlorobenzoate; 1-(4-chlorophenyl)ethan-1-one; 3-chloropyridine; 5-chloropyrimidine; iodobenzene; 4-iodobenortrifluoride; 3-iodobenzotrifluoride; 1-iodo-3,5-diflurobenzene; 4-iodobenzofluoride; 1-iodo-3-(trifluoromethyl)benzene; 1-iodo-3-chlorobenzene; 4-iodobenzamide; 1-iodo-4-methylbenzene; 1-iodo-4-methoxybenzene; 1-iodo-3-methoxybenzene; 1-iodo-3,5-dimethoxybenzene; 4-iodobenzonitrile; methyl 4-iodobenzoate; 1-(4-bromophenyl)ethan-1-one; 3-iodopyridine; and 5-iodopyrimidine.

6. The method of claim 1 , wherein the amine is a primary amine or a secondary amine.

7. The method of claim 6 , wherein the amine is selected from the group consisting of propylamine, cyclohexylamine, phenethylamine, pyridine-3-amine, furan-2-ylmethanamine, aniline, 4-fluoroaniline, pyrrolidine, piperidine, morpholine, 4-methyl-piperidine, piperdine-4-ol, piperidine-4-carbonitrile, methyl piperidine-4-carboxylate, cyclohexanamine, 3-aminopyridine, propan-1-amine, hexan-1-amine, and 2-phenylethan-1-amine.

8. The method of claim 1 , wherein the amine is present in a molar excess of the aryl halide present in the reaction mixture.

9. The method of claim 8 , wherein the amine is present in about 1.8 to about 5.5 molar excess of the aryl halide present in the reaction mixture.

10. The method of claim 1 , wherein the Ni(II) salt catalyst solution comprises an Ni(II) salt compound selected from a Nickel(II) bromide salt, glyme, or solvate; Nickel(II) chloride salt, glyme, or solvate; Nickel(II) fluoride salt, glyme, or solvate; or Nickel(II) iodide salt, glyme, or solvate; or combination thereof.

11. The method of claim 10 , wherein the Ni(II) salt compound is selected from the group consisting of NiBr 2 .glyme, NiCl 2 .6H 2 O, NiCl 2 .glyme, and NiBr 2 . 3H 2 O.

12. The method of claim 10 , wherein the Ni(II) salt compound is NiBr 2 .3H 2 O.

13. The method of claim 10 , wherein the Ni salt catalyst solution further comprises a polar solvent, and the Ni(II) salt compound is dissolved in the polar solvent.

14. The method of claim 13 , where the polar solvent is selected from the group consisting of N,N-dimethylacetamide, dimethyl sulfoxide, methanol, N,N-dimethylformamide, and acetonitrile.

15. The method of claim 14 , wherein the polar solvent is N,N-dimethylacetamide.

16. The method of claim 1 , wherein the optional additional base is selected from the group consisting of quinuclidine, morpholine, N,N-diisopropylethylamine, and triethylamine.

17. The method of claim 16 , wherein the optional additional base is quinuclidine.

18. The method of claim 1 , wherein the light is at about 365 nm or 405 nm.

19. A method for forming an aryl carbon-nitrogen bond, the method comprising:
contacting an aryl halide with at least about a 1.8 molar excess of an amine relative to the aryl halide, in the presence of a NiBr 2 .3H 2 O salt, optionally quinuclidine, and N,N-dimethylacetamide, thereby forming a reaction mixture, and
exposing the reaction mixture to light at about 365 nm or 405 nm under reaction conditions sufficient to form the aryl carbon-nitrogen bond;
wherein the formation of the aryl carbon-nitrogen bond is light-driven and Ni-catalyzed without the addition of a photoredox catalyst under said reaction conditions.

20. The method of claim 19 , wherein the reactions conditions comprise holding the reaction mixture under light exposure at between about room temperature and about 80° C. for between about 1 hour and about 20 hours such that at least about 50% reaction yield is obtained.

21. The method of claim 9 , wherein the amine is present in molar excess of the aryl halide such that reaction mixture does not include the optional additional base.

22. The method of claim 19 , wherein the amine is present in molar excess of the aryl halide such that the reaction mixture does not include the optional quinuclidine.

23. The method of claim 3 , wherein the formation of the aryl carbon-nitrogen bond is tolerant to oxygen and water in the reaction mixture such that the at least about 80% reaction yield is obtained under reactions conditions that comprise providing an oxygen sparge prior to light exposure to increase oxygen content of the reaction mixture, the use of a hydrated Ni(II) salt catalyst solution to provide water content to the reaction mixture, and combinations thereof.

Assignees

• Univ Colorado State Res Found

Inventors

• Miyake Garret
• Lim Chern-Hooi
• Kudisch Max
• Liu Bin

Classifications

• C07D295/073 Primary

  with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings · CPC title

• B01J2219/0877

  Liquid · CPC title

• B01J31/0271

  also containing elements or functional groups covered by B01J31/0201 - B01J31/0231 · CPC title

• B01J31/0204

  Ethers · CPC title

• C07C211/45

  Monoamines · CPC title