阅读说明：本技术 N-硫芳基苯磺酰亚胺及其制备方法和应用 (N-thioaryl benzenesulfonylimine and preparation method and application thereof ) 是由 陈志敏 张晔 罗会云 丁同梅 于 2019-04-24 设计创作，主要内容包括：本发明涉及N-硫芳基苯磺酰亚胺及其制备方法和应用,以双苯磺酰亚胺为原料,与氢化钠反应得到双苯磺酰亚胺的钠盐,制备得到的双苯磺酰亚胺的钠盐与苯(包括取代的苯基)次磺酰氯反应,得到N-硫芳基苯磺酰亚胺,可以在硫芳基化反应中应用。与现有技术相比,本发明反应条件温和,化学产率高,合成一类新的对水和空气都不敏感、稳定性较高的硫芳基试剂,制得的N-硫芳基苯磺酰亚胺可以用做活性较高的亲电性的硫芳基化试剂,具有很好的应用前景。(The invention relates to N-sulfoaryl benzenesulfonimide and a preparation method and application thereof. Compared with the prior art, the method has the advantages of mild reaction conditions, high chemical yield, synthesis of a new sulfur aryl reagent which is insensitive to water and air and has high stability, and application of the prepared N-sulfur aryl benzenesulfonimide as a sulfur arylating reagent with high activity and electrophilicity.)

An N-thioaryl benzenesulfonylimine characterized by the chemical formula (I):

2. the method for preparing N-thioaryl benzenesulfonylimine as claimed in claim 1, wherein the method comprises reacting diphenylsulfonimide as raw material with sodium hydride to obtain sodium salt of diphenylsulfonimide, and reacting with benzene sulfenyl chloride to obtain N-thioaryl benzenesulfonylimine.

3. The process for the preparation of an N-thioarylbenzenesulfonylimine as claimed in claim 2, comprising:

(1) uniformly mixing dry n-hexane and sodium hydride, standing, sucking supernatant, drying the residual n-hexane by using argon after repeating for a plurality of times, adding dry tetrahydrofuran under the protection of argon, dissolving the bis-benzenesulfonylimide in the dry tetrahydrofuran, slowly dripping the bis-benzenesulfonylimide into the sodium hydride, concentrating and performing vacuum pumping after the reaction is finished, and obtaining sodium salt of the bis-benzenesulfonylimide;

(2) dissolving sodium salt of the bis-phenylsulfonylimide in dry dichloromethane, slowly adding dichloromethane solution of benzene sulfenyl chloride in inert atmosphere for reaction, concentrating, performing column chromatography, concentrating, and pumping under an oil pump to obtain the N-sulfoaryl-phenylsulfonylimide.

4. The method for producing an N-thioarylbenzenesulfonylimide as claimed in claim 2 or 3, wherein the molar ratio of the bisbenzenesulfonylimide to sodium hydride is 10: 10-12.

5. The method for preparing N-thioarylbenzenesulfonylimine as claimed in claim 3, wherein in step (1), when reacting said bisbenzenesulfonylimine with sodium hydride, the reaction temperature is controlled at room temperature, the reaction pressure is normal pressure, the reaction time is 12-20h, the temperature is controlled at 10-30 ℃ during concentration, and the vacuum degree is controlled at 5-30mm Hg during pumping-out.

6. The method for preparing N-thioaryl benzenesulfonylimine according to claim 2 or 3, wherein the molar ratio of the sodium salt of bisbenzenesulfonylimine to benzenesulfonyl chloride is 10:10-13, and the benzenesulfonyl chloride comprises unsubstituted benzenesulfonyl chloride, ortho-methyl-substituted benzenesulfonyl chloride, meta-methyl-substituted benzenesulfonyl chloride, para-methoxy-substituted benzenesulfonyl chloride, para-fluoro-benzenesulfonyl chloride, 2, 6-dimethyl-substituted benzenesulfonyl chloride or benzylsulfenyl chloride.

7. The method for preparing N-thioarylbenzenesulfonylimine as claimed in claim 3, wherein in step (2), the dichloromethane solution of benzenesulfonyl chloride is slowly added under argon at-10-10 ℃ and reacted at the temperature for 0.5-3h, and then reacted at room temperature for 1-5 h.

8. The method for preparing N-thioaryl benzenesulfonylimine as claimed in claim 3, wherein the concentration in step (2) is performed at 10-35 deg.C, and silica gel is used for column chromatography, wherein the eluent is petroleum ether and ethyl acetate at a volume ratio of 30:1, and the vacuum degree is controlled at 5-25mmHg during draining.

9. The use of an N-thioarylbenzenesulfonylimine as claimed in claim 1 for sulfur arylation.

10. Use of an N-thioaryl benzenesulfonylimine as claimed in claim 9, wherein said thioarylation reaction comprises thioarylation/lactonization, thioarylation/etherification or thioarylation/1, 2-rearrangement reaction.

Technical Field

The invention belongs to the technical field of organic chemistry, and particularly relates to N-sulfoaryl benzenesulfonimide as well as a preparation method and application thereof.

Background

Organic sulfur compounds are a very important class of organic compounds. The compounds not only exist widely in active natural products and drug molecules, but also are very important intermediates, and can be quickly converted into other organic compounds and sulfides in other oxidation states. At present, the active electrophilic sulfur aryl reagents are limited and some are sensitive to water and air, and with the development of new drug development and release industries in China, the development of new electrophilic sulfur aryl reagents with good stability is very necessary, and the application of the electrophilic sulfur aryl reagents in the field of organic synthesis is more and more extensive.

Disclosure of Invention

The invention aims to overcome the defects in the prior art and provide a preparation method of N-sulfoaryl benzenesulfonimide with mild condition, good controllability, good stability and good repeatability and the N-sulfoaryl benzenesulfonimide prepared by the method, which can be applied to the sulfur arylation reaction.

The purpose of the invention can be realized by the following technical scheme:

an N-thioaryl benzenesulfonylimine having the formula (I):

the N-sulfoaryl benzenesulfonimide is a novel sulfoarylation reagent, and the prepared N-sulfoaryl benzenesulfonimide can be used as a high-activity electrophilic sulfoarylation reagent. Meanwhile, compared with the sulfur aryl reagent which is a linear sulfur aryl reagent and is previously a ring system, N-sulfur aryl benzene sulfonyl imide as the reagent has different steric hindrance, and has different regioselectivity in the reaction, and the selectivity is caused by the previous sulfur aryl reagent in some reactions.

The N-thioaryl benzenesulfonimide is prepared by the following method: the method comprises the following steps of reacting bisbenzenesulfonylimine serving as a raw material with sodium hydride to obtain sodium salt of the bisbenzenesulfonylimine, and reacting the prepared sodium salt of the bisbenzenesulfonylimine with benzene sulfenyl chloride to obtain the N-sulfoaryl benzenesulfonylimine, wherein the method specifically comprises the following steps:

(1) Uniformly mixing dry n-hexane and sodium hydride, standing, sucking supernatant, drying the residual n-hexane by using argon after repeating for a plurality of times, adding dry tetrahydrofuran under the protection of argon, dissolving the bis-benzenesulfonylimide in the dry tetrahydrofuran, slowly dripping the bis-benzenesulfonylimide into the sodium hydride, concentrating and performing vacuum pumping after the reaction is finished, and obtaining sodium salt of the bis-benzenesulfonylimide;

(2) dissolving sodium salt of the bis-phenylsulfonylimide in dry dichloromethane, slowly adding dichloromethane solution of benzene sulfenyl chloride in inert atmosphere for reaction, concentrating, performing column chromatography, concentrating, and pumping under an oil pump to obtain the N-sulfoaryl-phenylsulfonylimide.

In the step (1), the molar ratio of the bisbenzenesulfonylimide to the sodium hydride is 10:10-12, preferably 10: 10.5.

When reacting the bisbenzenesulfonylimine with sodium hydride, controlling the reaction temperature at room temperature, the reaction pressure at normal pressure, the reaction time at 5-25h, the temperature at 5-25 ℃ during concentration and the vacuum degree at 5-30mmHg during draining.

In the step (2), the molar ratio of the sodium salt of the bisbenzenesulfonylimide to the benzene sulfenyl chloride is 10:10-13, and preferably 10:10 can be adopted.

The benzene sulfenyl chloride comprises unsubstituted benzene sulfenyl chloride, ortho-methyl substituted benzene sulfenyl chloride, meta-methyl substituted benzene sulfenyl chloride, para-methoxy substituted benzene sulfenyl chloride, para-fluoro substituted benzene sulfenyl chloride, 2, 6-dimethyl substituted benzene sulfenyl chloride or benzyl sulfenyl chloride.

Slowly adding dichloromethane solution of benzene sulfenyl chloride at-10-10 ℃ under argon, reacting for 0.5-3h at the temperature, and reacting for 1-5h at room temperature. Concentrating at 10-35 deg.C, performing column chromatography with silica gel, eluting with petroleum ether and ethyl acetate at a volume ratio of 30:1, and vacuum-drying at 5-25 mmHg.

The whole preparation process can be represented by the reaction process:

the prepared N-sulfoaryl benzenesulfonimide can be applied to sulfur arylation reactions, including but not limited to sulfur arylation/lactonization, sulfur arylation/etherification or sulfur arylation/rearrangement reactions and the like.

Compared with the prior art, the invention has the following advantages:

1) the reaction condition is mild, the stability is good, and the reagent is insensitive to air, water and temperature, and is a novel thioarylation reagent. The activity of the raw material benzene sulfenyl chloride is high, so the reaction condition is mild, and compared with an S-Cl bond, a newly generated N-S bond is stable, and the stability of the newly generated N-thioaryl benzene sulfenyl imide is good and the odor of most sulfides is avoided.

2) The N-sulfur aryl benzene sulfonyl imide can be used as a sulfur arylation reagent with high activity and electrophilicity to be applied to sulfur arylation reaction, and has good application prospect. Currently, organic sulfur aryl compounds are synthesized by capturing cationic intermediates mainly through nucleophilic sulfur aryl groups to obtain corresponding target products. Many reactions require electrophilic sulfur aryl groups to initiate the reaction. However, the electrophilic thioarylation reaction has been slow in development because of the limited number of active electrophilic thioarylic reagents and the difficulty in handling and storing some reagents which are sensitive to water and air, and the synthesis of the reagents enables a large number of electrophilic thioarylation reactions. In the early reports, benzene sulfenyl chloride is mostly used directly, but the newly formed N-sulfur aryl benzene sulfenyl imine has good stability due to the more valence of sulfur, the instability of S-Cl bond and the stability of N-S bond. But in order to ensure the reactivity, the other group on the nitrogen is benzenesulfonyl, so that the structure ensures the reactivity and is insensitive to water and air.

Detailed Description

The present invention will be described in detail with reference to specific examples. The following examples will assist those skilled in the art in further understanding the invention, but are not intended to limit the invention in any way. It should be noted that variations and modifications can be made by persons skilled in the art without departing from the spirit of the invention. All falling within the scope of the present invention.

An N-thioaryl benzenesulfonylimine having the formula (I):

the N-sulfoaryl benzenesulfonimide is a novel sulfoarylation reagent, and the prepared N-sulfoaryl benzenesulfonimide can be used as a high-activity electrophilic sulfoarylation reagent.

The N-sulfoaryl benzenesulfonimide can be prepared by adopting a method with mild conditions:

(1) adding the dried n-hexane into a round-bottom flask filled with sodium hydride, shaking and standing for 10-15 minutes, sucking the supernatant and repeating for three times, and then blowing the rest n-hexane with argon. And then placing the round-bottom flask containing sodium hydride under argon protection, adding dry tetrahydrofuran, simultaneously dissolving the bis-benzenesulfonylimide in the dry tetrahydrofuran at room temperature, slowly dropwise adding the bis-benzenesulfonylimide into the round-bottom flask containing the sodium hydride, controlling the molar ratio of the bis-benzenesulfonylimide to the sodium hydride to be 10:10-12, continuing to react for 16 hours at room temperature, concentrating the system at 15 ℃, drying the system by using an oil pump, and controlling the vacuum degree to be about 20mmHg to obtain the sodium salt of the bis-benzenesulfonylimide.

(2) Dissolving the sodium salt of the bis-benzenesulfonylimine in dry dichloromethane, slowly adding a dichloromethane solution of benzene (including substituted phenyl) sulfenyl chloride in an inert atmosphere at 0 ℃ for reacting for 1 hour at the temperature, then reacting for 2 hours at room temperature, concentrating at low temperature, performing column chromatography, further concentrating, pumping by using an oil pump, and obtaining N-sulfoaryl benzenesulfonylimine which is light brown liquid at the vacuum degree of about 10 mmHg.

The invention has mild reaction conditions and high chemical yield, synthesizes a new thioarylation reagent, and can be applied to the thioarylation reaction, including but not limited to thioarylation/lactonization, thiocyanization/etherification or thioarylation/1, 2-rearrangement reaction and the like.

The following are further and more detailed embodiments.