阅读说明：本技术 一种利用微通道反应装置连续制备异苯并呋喃类化合物的方法 (Method for continuously preparing isobenzofuran compounds by using microchannel reaction device ) 是由 郭凯 卞米雪 方正 花加伟 刘成扣 欧阳平凯 于 2020-06-04 设计创作，主要内容包括：本发明公开了一种利用微通道反应装置连续制备异苯并呋喃类化合物的方法,将邻位乙烯基磺酰胺化合物1、二硒醚2和电解质溶于溶剂中,得到均相溶液；将均相溶液泵入到微通道反应装置中,进行连续电解反应,得到异苯并呋喃化合物3；所述的微通道反应装置为设有电极的微通道反应装置。与现有技术相比,本发明采用微通道反应装置,反应时间短,产物收率高,显著的提高了反应效率；同时,本发明无需添加昂贵的有机催化剂或金属催化剂,操作简便,绿色高效,成本低。(The invention discloses a method for continuously preparing isobenzofuran compounds by using a microchannel reaction device, which comprises the steps of dissolving ortho-vinyl sulfonamide compound 1, diselenide 2 and electrolyte in a solvent to obtain a homogeneous solution; pumping the homogeneous solution into a microchannel reaction device for continuous electrolytic reaction to obtain an isobenzofuran compound 3; the microchannel reaction device is provided with electrodes. Compared with the prior art, the method adopts the microchannel reaction device, has short reaction time and high product yield, and obviously improves the reaction efficiency; meanwhile, the method does not need to add expensive organic catalysts or metal catalysts, is simple and convenient to operate, is green and efficient, and is low in cost.)

1. A method for continuously preparing isobenzofuran compounds by using a microchannel reaction device is characterized in that ortho-vinyl sulfonamide compounds 1, diselenide 2 and electrolyte are dissolved in a solvent to obtain a homogeneous solution; pumping the homogeneous solution into a microchannel reaction device for continuous electrolytic reaction to obtain an isobenzofuran compound 3;

wherein R is₁Is selected from 4-methyl4-tert-butyl, 2-methyl; r₂Selected from hydrogen, 4-chloro, 2-chloro, 4-nitro, 4-methoxy, 2-methoxy, 3-methoxy;

wherein, the microchannel reaction device is provided with electrodes.

2. The method according to claim 1, wherein the concentration of the ortho-vinyl sulfonamide compound 1 in the homogeneous solution is 0.02-0.06 mmol/mL.

3. The method according to claim 1, wherein the concentration of diselenide 2 in the homogeneous solution is 0.01 to 0.09 mmol/mL.

4. The method of claim 1, wherein the concentration of the electrolyte in the homogeneous solution is 0.01 to 0.18 mmol/mL.

5. The method according to claim 1, wherein the solvent of the homogeneous solution is any one or a combination of acetonitrile, dichloroethane and hexafluoroisopropanol.

6. The method according to claim 1, wherein the electrolyte is any one or a combination of lithium perchlorate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium iodide, tetraethylammonium perchlorate and sodium iodide.

7. The method of claim 1, wherein the micro-reaction device comprises a pump, a cathode sheet, an anode sheet, a microchannel reactor, and a receiver; wherein, both sides of the microchannel reactor are respectively provided with a cathode sheet and an anode sheet; wherein the pump, the microchannel reactor and the receiver are connected in series, the connection being by tubing.

8. A method according to claim 7, wherein the cathode sheet is a platinum sheet and the anode sheet is a graphite sheet.

9. The method according to claim 1, wherein the current intensity of the electrolysis reaction is 5 to 20 mA.

10. The method of claim 1, wherein the temperature of the electrolysis reaction is room temperature; the reaction residence time is 0.25-5 min.

Technical Field

The invention belongs to the field of organic synthesis, and particularly relates to a method for continuously preparing an isobenzofuran compound by using a microchannel reaction device.

Background

Isobenzofuran is an important heterocyclic compound, and dihydroisobenzofuran, a derivative of the isobenzofuran, is a synthetic precursor of isobenzofuran and other important heterocyclic derivatives, and the dihydroisobenzofuran is started to be used as a synthetic intermediate for synthesizing a compound with biological activity, such as a pharmaceutical phenolphthalein tablet acting on colon, an antidepressant drug citalopram hydrobromide and the like. Meanwhile, isobenzofuran is also an important raw material for synthesizing bioactive substances and functional materials, particularly isobenzofuran has a diene structure and can generate Diels-Alder reaction, and the application range of isobenzofuran in organic synthesis is further enriched.

At present, the methods for preparing the isobenzofuran compounds mainly comprise metal catalysis, iodine catalysis, base catalysis, acid catalysis and the like. These methods are all important methods for synthesizing isobenzofuran derivatives, and some metals show good catalytic activity, so that a plurality of colorful compounds are synthesized. However, metals often show two sides in the synthesis, for example, many byproducts are generated, environmental pollution is caused, and the like. In addition, these methods have problems of long reaction time, high reaction temperature, expensive catalyst, many by-products, and the like.

With the development of green chemistry, electrochemistry has become an efficient synthesis method, which uses infinite electrons as reagents in the redox process, thereby avoiding the use of hazardous, costly and environmentally unfriendly oxidants and reductants. Therefore, electrosynthesis generally has high atom economy, avoids the generation of undesirable waste, and can greatly improve reaction yield, selectivity, safety, and product quality.

Disclosure of Invention

The purpose of the invention is as follows: the technical problem to be solved by the invention is to provide a method for continuously preparing an isobenzofuran compound by using a microchannel reaction device aiming at the defects of the prior art, so as to overcome the problems of long reaction process period and expensive catalyst requirement of the traditional oxidation system.

The invention idea is as follows: the microchannel reactor technology has gradually become a research hotspot in the technical field of international fine chemical engineering. A microchannel reactor is a three-dimensional structural element that can be used for chemical reactions, fabricated with a fixed matrix by means of special microfabrication techniques. Microchannel reactors typically contain very small channel sizes (equivalent diameters less than 500 μm) and channel diversity in which fluids flow, mix, and react. And therefore have a very large specific surface area (surface area/volume) in such a micro-structured chemical device. The advantages brought by this are the great mass and heat transfer efficiency, i.e. the precise control of the reaction temperature and the instantaneous mixing of the reaction mass in a precise ratio can be realized. These are all key to improving yield, selectivity, safety, and product quality. Therefore, the microchannel reactor used by the invention is a microchannel reactor with small channel diameter and high mass transfer efficiency. The isobenzofuran compound is quickly synthesized by using the microchannel reactor, so that the amplification reaction is facilitated, and the reaction process is safe, efficient and green.

In order to solve the technical problem, the invention discloses a method for continuously preparing an isobenzofuran compound by using a microchannel reaction device, which has the following reaction formula:

wherein R is₁Selected from 4-methyl, 4-tert-butyl, 2-methyl; r₂Selected from hydrogen, 4-chlorine, 2-chlorine, 4-nitro, 4-methoxy, 2-methoxy and 3-methoxy.

Specifically, dissolving ortho-vinyl sulfonamide compound 1, diselenide 2 and electrolyte in a solvent to obtain a homogeneous solution; opening the current of the microchannel reactor, pumping the homogeneous solution into the microchannel reactor, carrying out continuous electrolytic reaction, and collecting effluent liquid to obtain an isobenzofuran compound 3;

wherein R is₁Selected from 4-methyl, 4-tert-butyl, 2-methyl; r₂Is selected from 4-chlorine, 2-chlorine, 4-nitryl, 4-methoxyl, 2-methoxyl and 3-methoxyl.

Wherein, the microchannel reaction device is provided with electrodes.

Wherein the concentration of the ortho-vinyl sulfonamide compound 1 in the homogeneous solution is 0.02-0.06 mmol/mL, preferably 0.025 mmol/mL.

Wherein the concentration of the diselenide 2 in the homogeneous solution is 0.01-0.09 mmol/mL, preferably 0.025 mmol/mL.

Wherein the concentration of the electrolyte in the homogeneous solution is 0.01-0.18 mmol/mL, preferably 0.05 mmol/mL.

Wherein the mol ratio of the ortho-vinyl sulfonamide compound 1 to the diselenide 2 to the electrolyte is 1: 0.5-1.5: 0.5 to 3, preferably 1: 1: 2.

wherein, the solvent of the homogeneous solution is any one or a combination of more of acetonitrile, dichloroethane and hexafluoroisopropanol, and acetonitrile is preferred.

The electrolyte is any one or combination of more of lithium perchlorate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium iodide, tetraethylammonium perchlorate and sodium iodide, and preferably lithium perchlorate.

Wherein the micro-reaction device comprises a pump, a cathode sheet, an anode sheet, a micro-channel reactor and a receiver; wherein, both sides of the microchannel reactor are respectively provided with a cathode sheet and an anode sheet; wherein the pump, the microchannel reactor and the receiver are connected in series, the connection being by tubing.

The cathode sheet is a platinum sheet, and the anode sheet is a graphite plate.

Wherein the micro-channel reactor is manufactured by Syrris Ltd, named the Asia Flux module and has the Model No. 2200554.

Wherein the reaction volume of the microchannel reactor is 225 mu L.

Wherein the flow rate of the homogeneous solution pumped into the microchannel reactor is 45-900 mu L/min, preferably 450 mu L/min.

Wherein the current intensity of the electrolytic reaction is any one of 5-20 mA, preferably 15 mA.

Wherein the temperature of the electrolytic reaction is room temperature; the reaction residence time is 0.25 to 5min, preferably 15s to 1min, and more preferably 30 s.

Has the advantages that: compared with the prior art, the invention has the following advantages:

(1) the present invention reports for the first time the preparation of isobenzofuran compounds by electrochemical oxidation;

(2) the invention adopts a microchannel reaction device, has short reaction time and high product yield, and obviously improves the reaction efficiency;

(3) the method does not need to add expensive organic catalyst or metal catalyst, is simple and convenient to operate, is green and efficient, and has low cost;

(4) the invention continuously reacts through the injection pump and the microchannel reaction device, the preparation process is easy to operate and control, the reaction condition is mild, the safety is high, and the invention has better industrial amplification potential.

Drawings

The foregoing and/or other advantages of the invention will become further apparent from the following detailed description of the invention when taken in conjunction with the accompanying drawings.

FIG. 1 is a diagram of a microchannel electrosynthesis reaction apparatus according to the present invention.

FIG. 2 is a reaction scheme of the present invention.

Detailed Description

The invention will be better understood from the following examples. However, those skilled in the art will readily appreciate that the description of the embodiments is only for illustrating the present invention and should not be taken as limiting the invention as detailed in the claims.

Using the apparatus diagram of FIG. 1, the microchannel reactor described in the following examples was manufactured by the manufacturer of the Syrris Ltd, entitled the Asia Flux Module, Model No. 2200554.

As shown in fig. 2, the following steps are followed: (1) adding the homogeneous solution A prepared in proportion into an injection pump a; (2) injecting the mixture into a microchannel reaction device by an injection pump according to a certain proportion for mixing and reacting; (3) adjusting the required current; (4) collecting the effluent reaction liquid, and calculating the product yield by a column-passing weighing method; and measuring the product yield by a high performance liquid chromatography, and separating by column chromatography to obtain the target product.

Wherein, the isobenzofuran compounds shown in table 1 are all products synthesized by the method of the invention, and are confirmed by nuclear magnetic characterization.

TABLE 1 Isobenzofuran Compounds of the invention

TABLE 2 reactants of the invention