阅读说明：本技术 一种光催化叔胺类化合物的合成方法 (Synthesis method of photocatalytic tertiary amine compound ) 是由 刘运奎 鲍汉扬 郑立孟 于 2019-08-27 设计创作，主要内容包括：本发明公开了一种光催化叔胺类化合物的合成方法,所述的方法具体按如下步骤进行：将光敏剂、碱性物质加入Schlenk反应管中,在氮气气氛下,再将式I、式II或式III所示烯烃和式IV所示叔胺溶解于有机溶剂中得到混合液,将所述的混合液加入到上述反应管中,在光源照射下,于25℃搅拌反应6～14小时,得到反应液经后处理分别得到式V、VI或VII所示的叔胺类化合物；所述的光敏剂、碱性物质、式I或式II或式III所示的烯烃及式IV所示的叔胺物质的量之比为0.05:1～2:1:1.5～2.5。本发明所述的方法可以合成现存的方法难以制备的叔胺；以廉价易得的铜基催化剂取代了贵金属催化剂,毒性较低；具有反应条件较温和,节约能源消耗；产率高,底物普适性强,操作简便等优点。(The invention discloses a method for synthesizing a photocatalytic tertiary amine compound, which comprises the following steps: adding a photosensitizer and an alkaline substance into a Schlenk reaction tube, dissolving olefin shown in formula I, formula II or formula III and tertiary amine shown in formula IV into an organic solvent under the atmosphere of nitrogen to obtain a mixed solution, adding the mixed solution into the reaction tube, stirring and reacting for 6-14 hours at 25 ℃ under the irradiation of a light source to obtain a reaction solution, and performing post-treatment on the reaction solution to respectively obtain tertiary amine compounds shown in formula V, VI or VII; the ratio of the amount of the photosensitizer, the alkaline substance, the olefin shown in formula I or formula II or formula III and the tertiary amine substance shown in formula IV is 0.05: 1-2: 1: 1.5-2.5. The method of the invention can synthesize tertiary amine which is difficult to prepare by the existing method; the cheap and easily obtained copper-based catalyst replaces a noble metal catalyst, so that the toxicity is low; the reaction conditions are mild, and the energy consumption is saved; high yield, strong substrate universality, simple and convenient operation and the like.)

1. a method for synthesizing a photocatalytic tertiary amine compound is characterized by comprising the following steps: the method comprises the following steps:

adding a photosensitizer and an alkaline substance into a Schlenk reaction tube, dissolving olefin shown in formula I, formula II or formula III and tertiary amine shown in formula IV into an organic solvent under the atmosphere of nitrogen to obtain a mixed solution, adding the mixed solution into the reaction tube, stirring and reacting for 6-14 hours at 25 ℃ under the irradiation of a light source to obtain a reaction solution, and carrying out post-treatment on the reaction solution to obtain a tertiary amine compound shown in formula V, VI or VII; the amount ratio of the photosensitizer to the alkaline substance to the olefin shown in formula I or formula II or formula III to the tertiary amine substance shown in formula IV is 0.05: 1-2: 1: 1.5-2.5;

the photosensitizer is one of the following structures:

formula I, formula IV, formula V, formula VI or formula VII:

R₁is Ph,

R₂is one of H and 2-pyridyl;

R₃is one of H and methyl;

R₄is one of methyl and ethyl;

R₅is one of ethyl and phenyl.

2. The method of claim 1, wherein: the olefin shown in the formula I is one of the following structures:

3. the method of claim 1, wherein: the tertiary amine shown in the formula IV is one of the following structures:

4. the method of claim 1, wherein: the alkaline substance is one of potassium acetate, potassium carbonate, sodium bicarbonate, potassium fluoride, cesium carbonate or potassium tert-butoxide.

5. The method of claim 1, wherein: the photosensitizer is

6. The method of claim 1, wherein: the organic solvent is one of tetrahydrofuran, 1, 4-dioxane, ethyl acetate and acetonitrile.

7. The method of claim 1, wherein: the total amount of the organic solvent added is 10mL/mmol based on the amount of the alkyne compound shown in the formula I, the formula II or the formula III.

8. The method of claim 1, wherein: the light source is one of a 15W blue LED, a 30W blue LED, a 60WCFL or a 20W white LED.

9. The method of claim 1, wherein: the ratio of the quantity of the photosensitizer, the alkaline substance, the olefin shown in formula I or formula II or formula III and the tertiary amine substance shown in formula IV is 0.05: 1.5: 1: 2.0.

10. the method of claim 1, wherein: the post-treatment method of the reaction solution comprises the following steps: and after the reaction is finished, adding 100-200-mesh column chromatography silica gel into the obtained reaction liquid, distilling under reduced pressure to remove the solvent, carrying out silica gel column chromatography separation on the obtained crude product, eluting by using petroleum ether/ethyl acetate (8/1) as an eluent, tracking the elution process by TLC (thin layer chromatography), collecting eluent containing the target product, combining the eluents, and distilling off the solvent to obtain the tertiary amine compound shown in the formula V, VI or VII.

(I) technical field

The invention relates to a synthetic method of an organic compound, in particular to a synthetic method of a photocatalytic tertiary amine compound.

(II) background of the invention

Tertiary amine has unique physiological activity, is the most important structural unit in medicinal chemistry, and is widely present in various medicinal molecules as shown in formulas 1-4. The classical methods for synthesizing tertiary amines are mainly N-alkylation and reductive amination. The synthesis of tertiary amines by these two methods often requires tedious steps and cumbersome post-treatments, which seriously hampers the progress of new drug development. With the development of transition metal catalytic reaction, various methods for synthesizing amine compounds from raw materials of sp2 hybrid systems, such as Buchwald-Hartwig amination and olefin hydroamination, have been established, but the strategy for synthesizing complex alkyl amines is very limited. Therefore, the development of a method for directly synthesizing complex tertiary amine compounds from simple and easily available raw materials has profound influence on both the synthetic chemical field and the pharmaceutical chemical field.

The C-H bond is the most common chemical bond in organic molecules, and the selective functionalization reaction of the C-H bond catalyzed by transition metal is a hot point of research in recent years due to atom economy and step economy.

Disclosure of the invention

Aiming at the defects in the prior art, the invention aims to provide a method for synthesizing a photocatalytic tertiary amine compound.

A method for synthesizing a photocatalytic tertiary amine compound is characterized by comprising the following steps: the method is specifically carried out according to the following steps:

adding a photosensitizer and an alkaline substance into a Schlenk reaction tube, dissolving olefin shown in formula I, formula II or formula III and tertiary amine shown in formula IV into an organic solvent under the atmosphere of nitrogen to obtain a mixed solution, adding the mixed solution into the reaction tube, stirring and reacting for 6-14 hours (preferably 12 hours) at 25 ℃ under the irradiation of a light source to obtain a reaction solution, and performing post-treatment on the reaction solution to respectively obtain tertiary amine compounds shown in formula V, VI or VII; the amount ratio of the photosensitizer to the alkaline substance to the olefin shown in formula I or formula II or formula III to the tertiary amine substance shown in formula IV is 0.05: 1-2: 1: 1.5-2.5 (preferably 0.05: 1.5: 1: 2.0);

the photosensitizer is one of the following structures:

formula I, formula IV, formula V, formula VI or formula VII:

R₁is Ph,

2-naphthyl, 4-bromophenyl, 1- (4-bromophenyl) ethenyl;

R₂is one of H and 2-pyridyl;

R₃is one of H and methyl;

R₄is one of methyl and ethyl;

R₅is one of ethyl and phenyl.

Further, the olefin represented by formula I is preferably one of the following structures:

further, the tertiary amine represented by formula IV of the present invention is preferably one of the following structures:

further, the basic substance in the present invention is one of potassium acetate, potassium carbonate, sodium hydrogen carbonate, potassium fluoride, cesium carbonate, and potassium tert-butoxide, and further, cesium carbonate is preferable.

Further, the photosensitizer is preferably

Further, the organic solvent is one of tetrahydrofuran, 1, 4-dioxane, ethyl acetate and acetonitrile; still more preferably, acetonitrile is used.

Further, the total amount of the organic solvent added is 10mL/mmol based on the amount of the substance of the alkyne compound shown in formula I, formula II or formula III.

Further, the light source is one of a 15W blue LED, a 30W blue LED, a 60W CFL and a 20W white LED.

Further, the light source is preferably a 15W blue LED.

Further, the post-treatment method of the reaction solution comprises the following steps: and after the reaction is finished, adding 100-200-mesh column chromatography silica gel into the obtained reaction liquid, distilling under reduced pressure to remove the solvent, carrying out silica gel column chromatography separation on the obtained crude product, eluting by using petroleum ether/ethyl acetate (8/1) as an eluent, tracking the elution process by TLC (thin layer chromatography), collecting eluent containing the target product, combining the eluents, and distilling off the solvent to obtain the tertiary amine compound shown in the formula V, VI or VII.

Compared with the prior art, the invention has the beneficial effects that:

the method of the invention can synthesize tertiary amine which is difficult to prepare by the existing method; the cheap and easily obtained copper-based catalyst replaces a noble metal catalyst, so that the toxicity is low; the reaction conditions are mild, and the energy consumption is saved; high yield, strong substrate universality, simple and convenient operation and the like.

(IV) detailed description of the preferred embodiment

The invention will be further illustrated by the following examples, without limiting the scope of the invention:

the copper-based photosensitizers described in this application were synthesized according to literature methods (see angelw. chem. int. ed.2013,52,419.) general procedure: to a dry Schlenk reaction tube, [ Cu (MeCN) ]was added₄]PF₆(1equiv.) and the corresponding phosphine ligand (1equiv.), nitrogen was charged three times, dichloromethane (concentration 0.05 mol/L) was added under nitrogen, and the reaction was stirred under reflux overnight. The corresponding nitrogen ligand (1equiv.) was dissolved in as little dichloromethane as possible and then added to the Schlenk reaction tube and stirred under reflux for 3 hours. After the reaction is finished, cooling the reaction liquid to room temperature, adding n-hexane to separate out the product, filtering, washing a filter cake with n-pentane, and drying under vacuum to obtain the product.