CN104072397A

CN104072397A - Synthesis method for aziridine derivative

Info

Publication number: CN104072397A
Application number: CN201410319075.6A
Authority: CN
Inventors: 刘海波
Original assignee: TAICANG BOYI CHEMICAL Co Ltd
Current assignee: TAICANG BOYI CHEMICAL Co Ltd
Priority date: 2014-07-07
Filing date: 2014-07-07
Publication date: 2014-10-01

Abstract

The invention discloses a synthesis method for an aziridine derivative. The synthesis method comprises the steps of adding phenyl isothiocyanate and an organic solvent into a reactor with a reflux condensing tube under the protection of N2, adding 2-bromine allyl amine, stirring at room temperature till the raw materials are dissolved completely, then adding cuprous iodide and alkali metal salt, stirring and heating up to 60-120DEG C, tracking the reaction process by thin layer chromatography till an intermediate thiourea disappears completely, after reacting, cooling the mixture to room temperature, adding a saturated ammonium chloride solution while stirring, extracting the mixture for many times by ethyl acetate, washing the organic layer by saturated salt water, then drying by anhydrous sodium sulfate, after rotary evaporation and concentration, and carrying out separation on columns by silica gel, so as to obtain the target product. The synthesis method for the aziridine derivative has the characteristics of easy availability of raw materials, simple operation, mild reaction conditions and the like, and is applicable to large-scale production.

Description

A kind of synthetic method of aziridine derivative

Technical field

The invention belongs to fine chemical technology field, relate to a kind of synthetic method of aziridine derivative.

Background technology

Aziridine, because its unique structure is a kind of important industrial chemicals and organic intermediate, is also the front body structure of a lot of synthetic drugss.1901, Germanization scholar Liv Ullmann was found the linked reaction under copper catalysis, and the Ullmann linked reaction of after this copper catalysis is the problem that organic chemists study always.In recent years, by synthetic some heterogeneous ring compound of copper catalyzed coupling reaction, become the focus of research, but be not yet seen in report by the method for synthetic aziridines compound under copper catalysis.

Summary of the invention

In view of this, the object of the present invention is to provide a kind of novel synthesis of aziridine derivative.

For achieving the above object, the invention provides following technical scheme:

A synthetic method for aziridine derivative, comprises the steps:

At N ₂under protection, to being furnished with in the reaction unit of reflux condensing tube, add PITC and organic solvent, add 2-bromine allylamine, under room temperature, stir until raw material completely dissolve, add again cuprous iodide, an alkali metal salt, stir and be warming up to 60 ~ 120 ℃, with tlc, follow the tracks of reaction process until the completely dissolve of intermediate thiocarbamide, reaction finishes, mixture is cooled to room temperature, under stirring, add saturated ammonium chloride solution, mixture is extracted with ethyl acetate repeatedly, organic layer saturated common salt water washing, again through anhydrous sodium sulfate drying, after rotary evaporation is concentrated, with silica gel, carry out post separation, obtain target product.

In technique scheme, described organic solvent is any one in DMF, DMSO, THF.

In technique scheme, the consumption of described cuprous iodide catalyst is reaction substrate amount of substance 5 ~ 20%.

In technique scheme, described an alkali metal salt is salt of wormwood or cesium carbonate, and its consumption is reaction substrate 100 ~ 200%.

Preferably, add after cuprous iodide, an alkali metal salt, stir and be warming up to 100 ℃.

The features such as the synthetic method of aziridine derivative of the present invention has raw material and is easy to get, simple to operate, and reaction conditions is comparatively gentle, and applicable large-scale production.

Embodiment

Below the technical scheme in the embodiment of the present invention is described in detail, obviously, described embodiment is only the present invention's part embodiment, rather than whole embodiment.Embodiment based in the present invention, the every other embodiment that those of ordinary skills obtain under the prerequisite of not making creative work, belongs to the scope of protection of the invention.

Embodiment 1

At N ₂under protection, to being furnished with in the reaction unit of reflux condensing tube, add 1mol PITC and 5L organic solvent DMSO, add 1mol 2-bromine allylamine, under room temperature, stir until raw material completely dissolve, add again 0.05mol cuprous iodide, 1mol an alkali metal salt, stir and be warming up to 60 ℃, with tlc, follow the tracks of reaction process until the completely dissolve of intermediate thiocarbamide, reaction finishes, mixture is cooled to room temperature, under stirring, add saturated ammonium chloride solution, mixture is extracted with ethyl acetate repeatedly, organic layer saturated common salt water washing, again through anhydrous sodium sulfate drying, after rotary evaporation is concentrated, with silica gel, carry out post separation, obtain target product.

Embodiment 2

At N ₂under protection, to being furnished with in the reaction unit of reflux condensing tube, add 1mol PITC and 5L organic solvent DMF, add 1mol 2-bromine allylamine, under room temperature, stir until raw material completely dissolve, add again 0.1mol cuprous iodide, 1.5mol an alkali metal salt, stir and be warming up to 100 ℃, with tlc, follow the tracks of reaction process until the completely dissolve of intermediate thiocarbamide, reaction finishes, mixture is cooled to room temperature, under stirring, add saturated ammonium chloride solution, mixture is extracted with ethyl acetate repeatedly, organic layer saturated common salt water washing, again through anhydrous sodium sulfate drying, after rotary evaporation is concentrated, with silica gel, carry out post separation, obtain target product.

Embodiment 3

At N ₂under protection, to being furnished with in the reaction unit of reflux condensing tube, add 1mol PITC and 5L organic solvent THF, add 1mol 2-bromine allylamine, under room temperature, stir until raw material completely dissolve, add again 0.2mol cuprous iodide, 2mol an alkali metal salt, stir and be warming up to 120 ℃, with tlc, follow the tracks of reaction process until the completely dissolve of intermediate thiocarbamide, reaction finishes, mixture is cooled to room temperature, under stirring, add saturated ammonium chloride solution, mixture is extracted with ethyl acetate repeatedly, organic layer saturated common salt water washing, again through anhydrous sodium sulfate drying, after rotary evaporation is concentrated, with silica gel, carry out post separation, obtain target product.

In those skilled in the art, obviously the invention is not restricted to the details of above-mentioned one exemplary embodiment, and in the situation that not deviating from spirit of the present invention or essential characteristic, can realize the present invention with other specific form.Therefore, no matter from which point, all should regard embodiment as exemplary, and be nonrestrictive, scope of the present invention is limited by claims rather than above-mentioned explanation, is therefore intended to include in the present invention dropping on the implication that is equal to important document of claim and all changes in scope.

In addition, be to be understood that, although this specification sheets is described according to embodiment, but not each embodiment only comprises an independently technical scheme, this narrating mode of specification sheets is only for clarity sake, those skilled in the art should make specification sheets as a whole, and the technical scheme in each embodiment also can, through appropriately combined, form other embodiments that it will be appreciated by those skilled in the art that.

Claims

1. a synthetic method for aziridine derivative, is characterized in that, comprises the steps: at N ₂under protection, to being furnished with in the reaction unit of reflux condensing tube, add PITC and organic solvent, add 2-bromine allylamine, under room temperature, stir until raw material completely dissolve, add again cuprous iodide, an alkali metal salt, stir and be warming up to 60 ~ 120 ℃, with tlc, follow the tracks of reaction process until the completely dissolve of intermediate thiocarbamide, reaction finishes, mixture is cooled to room temperature, under stirring, add saturated ammonium chloride solution, mixture is extracted with ethyl acetate repeatedly, organic layer saturated common salt water washing, again through anhydrous sodium sulfate drying, after rotary evaporation is concentrated, with silica gel, carry out post separation, obtain target product.

2. the synthetic method of aziridine derivative according to claim 1, is characterized in that: described organic solvent is any one in DMF, DMSO, THF.

3. the synthetic method of aziridine derivative according to claim 1, is characterized in that: the consumption of described cuprous iodide catalyst is reaction substrate amount of substance 5 ~ 20%.

4. the synthetic method of aziridine derivative according to claim 1, is characterized in that: described an alkali metal salt is salt of wormwood or cesium carbonate, and its consumption is reaction substrate 100 ~ 200%.

5. the synthetic method of aziridine derivative according to claim 1, is characterized in that: add after cuprous iodide, an alkali metal salt, stir and be warming up to 100 ℃.