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CN-122010747-A - Photochemical synthesis method of fluorine-containing tertiary amine

CN122010747ACN 122010747 ACN122010747 ACN 122010747ACN-122010747-A

Abstract

A photochemical synthesis method of fluorine-containing tertiary amine belongs to the field of organic synthesis. The invention aims to solve the problem that the prior art needs multiple steps of synthesis and complicated purification steps for obtaining the fluorine-containing tertiary amine compound. The method comprises the steps of uniformly mixing (2, 2-difluoroethylene-1, 1-diyl) diphenyl, dibenzylamine, 3-phenylpropionaldehyde, a catalyst, lewis acid, diethyl 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylic acid and an organic solvent, and then irradiating by a blue light lamp. The invention is used for photochemical synthesis of fluorine-containing tertiary amine.

Inventors

  • LIU XIAONAN
  • LUO JI
  • WANG JUNLEI

Assignees

  • 贵州医科大学
  • 贵州民族大学

Dates

Publication Date
20260512
Application Date
20260129

Claims (10)

  1. 1. A photochemical synthesis method of tertiary amine containing fluorine is characterized by comprising the following steps: Uniformly mixing (2, 2-difluoroethylene-1, 1-diyl) diphenyl, dibenzylamine, 3-phenylpropionaldehyde, a catalyst, lewis acid, diethyl 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylate and an organic solvent under the condition of nitrogen atmosphere, room temperature and stirring to obtain a mixture, carrying out photocatalysis reaction on the mixture under the condition of blue light irradiation and stirring with the wavelength of 450nm at the nitrogen atmosphere, carrying out reduced pressure distillation to remove the solvent after the reaction, and separating and purifying by silica gel column chromatography to obtain fluorine-containing tertiary amine, thereby completing the photochemical synthesis method of the fluorine-containing tertiary amine; The structural formula of the (2, 2-difluoroethylene-1, 1-diyl) diphenyl is ; The molar ratio of the (2, 2-difluoroethylene-1, 1-diyl) diphenyl to the dibenzylamine is 1 (1.0-1.5), the molar ratio of the (2, 2-difluoroethylene-1, 1-diyl) diphenyl to the 3-phenylpropionaldehyde is 1 (1.0-1.5), the molar ratio of the (2, 2-difluoroethylene-1, 1-diyl) diphenyl to the catalyst is 1 (0.01-0.03), the molar ratio of the (2, 2-difluoroethylene-1, 1-diyl) diphenyl to the Lewis acid is 1 (0.3-0.5), and the molar ratio of the (2, 2-difluoroethylene-1, 1-diyl) diphenyl to the diethyl 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylate is 1 (1.5-2.0).
  2. 2. The method for photochemistry synthesis of tertiary amine containing fluorine according to claim 1, wherein the organic solvent is acetonitrile, anhydrous dichloroethane, toluene, N-dimethylformamide or anhydrous dimethyl sulfoxide.
  3. 3. The photochemical synthesis method of fluorine-containing tertiary amine according to claim 1, wherein the volume ratio of the mol of (2, 2-difluoroethylene-1, 1-diyl) diphenyl to the organic solvent is 1mmol (5-10) mL.
  4. 4. The method for photochemically synthesizing a tertiary amine containing fluorine according to claim 1, wherein the catalyst is 4Cz-IPN、Ir(dFCF 3 ppy) 2 dtbpyPF 6 、Ir(dFppy) 2 bpyPF 6 、Ir(dFCF 3 ppy) 2 bpyPF 6 or Ir (dFppy) 2 dtbpyPF 6 .
  5. 5. The method for photochemistry synthesis of tertiary amine containing fluorine according to claim 1, wherein the lewis acid is trifluoroacetic acid, boron trifluoride diethyl ether, lithium chloride, sodium triflate, sodium tetrafluoroborate or p-toluenesulfonic acid.
  6. 6. The photochemical synthesis method of tertiary amine containing fluorine according to claim 1, wherein the solvent used for separation and purification by silica gel column chromatography is a mixed solvent of petroleum ether and ethyl acetate.
  7. 7. The photochemical synthesis method of fluorine-containing tertiary amine according to claim 6, wherein the volume ratio of petroleum ether to ethyl acetate is (100-110): 1.
  8. 8. The photochemical synthesis method of tertiary amine containing fluorine according to claim 1, wherein (2, 2-difluoroethylene-1, 1-diyl) diphenyl, dibenzylamine, 3-phenylpropionaldehyde, a catalyst, lewis acid, diethyl 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylate and an organic solvent are mixed for 20h to 24h under the conditions of nitrogen atmosphere, room temperature and stirring speed of 200r/min to 300r/min, so as to obtain a mixture.
  9. 9. The photochemical synthesis method of tertiary amine containing fluorine according to claim 1, wherein the mixture is subjected to photocatalytic reaction for 70-74 h under the conditions of nitrogen atmosphere, room temperature, wavelength of 450nm and power of 10-14W and stirring speed of 200-300 r/min.
  10. 10. The method for photochemically synthesizing a tertiary amine containing fluorine according to claim 1, wherein the tertiary amine containing fluorine is N, N-dibenzyl-2-fluoro-1, 5-triphenylpent-1-en-3-amine, and has a structural formula of 。

Description

Photochemical synthesis method of fluorine-containing tertiary amine Technical Field The invention belongs to the field of organic synthesis. Background The fluorine-containing tertiary amine compound has special biological and chemical properties, so that the fluorine-containing tertiary amine compound has wide application in medicines, pesticides and functional materials, such as medicines of posaconazole, erythromycin, fluoxetine and the like, and has good biological activity in the aspects of resisting bacteria, resisting depression, resisting fungi, resisting cancer, treating diabetes mellitus and the like. Research shows that introducing fluorine atom or fluorine-containing group into medicine molecule can raise its metabolic stability, liposolubility and bioactivity obviously. Traditional reductive amination and substitution reactions have great limitations in the synthesis of branched tertiary amines, while hydroamination of amines and olefins requires substrate molecules of specific structures to react, and the multi-step synthesis and cumbersome purification steps required to obtain these molecules severely hamper the development and progress of the drug. Disclosure of Invention The invention aims to solve the problems that the prior art needs multiple steps of synthesis and complicated purification steps for obtaining the fluorine-containing tertiary amine compound, and further provides a photochemical synthesis method for the fluorine-containing tertiary amine. A photochemical synthesis method of tertiary amine containing fluorine is carried out according to the following steps: Uniformly mixing (2, 2-difluoroethylene-1, 1-diyl) diphenyl, dibenzylamine, 3-phenylpropionaldehyde, a catalyst, lewis acid, diethyl 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylate and an organic solvent under the condition of nitrogen atmosphere, room temperature and stirring to obtain a mixture, carrying out photocatalysis reaction on the mixture under the condition of blue light irradiation and stirring with the wavelength of 450nm at the nitrogen atmosphere, carrying out reduced pressure distillation to remove the solvent after the reaction, and separating and purifying by silica gel column chromatography to obtain fluorine-containing tertiary amine, thereby completing the photochemical synthesis method of the fluorine-containing tertiary amine; The structural formula of the (2, 2-difluoroethylene-1, 1-diyl) diphenyl is ; The molar ratio of the (2, 2-difluoroethylene-1, 1-diyl) diphenyl to the dibenzylamine is 1 (1.0-1.5), the molar ratio of the (2, 2-difluoroethylene-1, 1-diyl) diphenyl to the 3-phenylpropionaldehyde is 1 (1.0-1.5), the molar ratio of the (2, 2-difluoroethylene-1, 1-diyl) diphenyl to the catalyst is 1 (0.01-0.03), the molar ratio of the (2, 2-difluoroethylene-1, 1-diyl) diphenyl to the Lewis acid is 1 (0.3-0.5), and the molar ratio of the (2, 2-difluoroethylene-1, 1-diyl) diphenyl to the diethyl 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylate is 1 (1.5-2.0). The beneficial effects of the invention are as follows: The invention provides a photochemical synthesis method of fluorine-containing tertiary amine under mild conditions, which has good application prospect in biomedical synthesis, has simple and mild reaction conditions, easily obtained raw materials, up to 77 percent of yield and up to 99 percent of purity, and is an ideal and practical photochemical synthesis method of fluorine-containing tertiary amine. Drawings FIG. 1 is a 1H NMR spectrum of a fluorine-containing tertiary amine prepared in example one; FIG. 2 is a 13C NMR spectrum of fluorine-containing tertiary amine prepared in example one; FIG. 3 is a 19F NMR spectrum of fluorine-containing tertiary amine prepared in example one. Detailed Description The first embodiment is a photochemical synthesis method of tertiary amine containing fluorine, which comprises the following steps: Uniformly mixing (2, 2-difluoroethylene-1, 1-diyl) diphenyl, dibenzylamine, 3-phenylpropionaldehyde, a catalyst, lewis acid, diethyl 2, 6-dimethyl-1, 4-dihydro-3, 5-pyridinedicarboxylate and an organic solvent under the condition of nitrogen atmosphere, room temperature and stirring to obtain a mixture, carrying out photocatalysis reaction on the mixture under the condition of blue light irradiation and stirring with the wavelength of 450nm at the nitrogen atmosphere, carrying out reduced pressure distillation to remove the solvent after the reaction, and separating and purifying by silica gel column chromatography to obtain fluorine-containing tertiary amine, thereby completing the photochemical synthesis method of the fluorine-containing tertiary amine; The structural formula of the (2, 2-difluoroethylene-1, 1-diyl) diphenyl is ; The molar ratio of the (2, 2-difluoroethylene-1, 1-diyl) diphenyl to the dibenzylamine is 1 (1.0-1.5), the molar ratio of the (2, 2-difluoroethylene-1, 1-diyl) diphenyl to the 3-phenylpropionaldehyde is 1 (1.0-1.5), the