阅读说明：本技术 一种1-磺酰甲基-3,4-二氢萘的制备方法 (Preparation method of 1-sulfonylmethyl-3, 4-dihydronaphthalene ) 是由 刘宇 王巧林 陈赞 唐课文 熊碧权 于 2019-06-06 设计创作，主要内容包括：本发明公开了一种制备1-磺酰甲基取代的3,4-二氢萘类化合物的合成途径。在可见光介导下,由乙烯基环丙烷类化合物与磺酰氯反应合成1-磺酰甲基取代的3,4-二氢萘类化合物。该方法具有反应条件温和、底物适应范围广、目标产物收率高等优点。(The invention discloses a synthetic route for preparing 1-sulfonyl methyl substituted 3, 4-dihydronaphthalene compounds. Under the mediation of visible light, vinyl cyclopropane compounds and sulfonyl chloride react to synthesize 1-sulfonyl methyl substituted 3, 4-dihydronaphthalene compounds. The method has the advantages of mild reaction conditions, wide substrate application range, high yield of target products and the like.)

1. A process for preparing a 1-sulfonylmethyl-substituted 3, 4-dihydronaphthalene compound of formula III comprising the steps of:

Sequentially adding a vinyl cyclopropane compound shown in a formula I, sulfonyl chloride shown in a formula II, a photocatalyst, alkali and an organic solvent into a Schlenk tube sealing reactor, then protecting the reactor with an inert atmosphere, placing the reactor in an oil bath kettle at 90-110 ℃ under the illumination condition, stirring and reacting for 12-36 h, detecting the reaction completely by TLC and/or GC-MS, and carrying out post-treatment to obtain a target product shown in a formula III;

Wherein, in the formula I and the formula III, the structural units represent aryl of C6-C20 and heteroaryl of C3-C20; r1 represents one or more substituents on the structural unit, each R1 substituent being independently selected from hydrogen, C1-C20 alkyl, C1-C20 alkoxy, C6-C20 aryl, nitro, halogen, -CN;

In the formulas II and III, R2 is selected from C1-C20 alkyl, substituted or unsubstituted C6-C20 aryl, and C3-C20 heteroaryl; and wherein the substituents in said "substituted or unsubstituted" are selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, nitro, C1-C6 acyl, -CN;

wherein the photocatalyst is any one of Ru (bpy)3Cl2, Ir (ppy)3, Eosin Y and Na2-Eosin Y;

The alkali is selected from any one of 2, 6-lutidine, K2CO3, Na2CO3, Cs2CO3, pyridine or triethylamine;

the organic solvent is selected from any one of 1, 4-dioxane, THF, DMF, DMSO, toluene and acetonitrile;

The illumination condition is provided by a 5W blue LED lamp, a 3W blue LED lamp, a 36W fluorescent lamp or a 5W green LED lamp.

2. the method of claim 1, wherein: in the formula I and the formula III, the structural units represent aryl of C6-C14 and heteroaryl of C3-C12; r1 represents one or more substituents on the structural unit, each R1 substituent being independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C6-C14 aryl, nitro, halogen, -CN;

In the formulas II and III, R2 is selected from C2-C12 alkyl, substituted or unsubstituted C6-C14 aryl, and C3-C12 heteroaryl; and wherein the substituents in the "substituted or unsubstituted" are selected from halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, nitro, C1-C6 acyl, -CN.

3. the method of claim 1, wherein: the compound of formula I is selected from compounds having the following structure:

；

The compound of formula II is selected from compounds having the following structure:

。

4. a method according to any one of claims 1-3, characterized in that: the photocatalyst is selected from Ru (bpy)3Cl 2;

The alkali is selected from 2, 6-dimethyl pyridine;

the organic solvent is selected from 1, 4-dioxane;

The illumination condition is provided by a 5W blue LED lamp.

5. a method according to any one of claims 1-3, characterized in that: the inert atmosphere is argon atmosphere or nitrogen atmosphere, preferably argon atmosphere.

6. A method according to any one of claims 1-3, characterized in that: the reaction time of the reaction is preferably 24 hours, and the reaction temperature is preferably 100 ℃.

7. A method according to any one of claims 1-3, characterized in that: the molar ratio of the vinyl cyclopropane compound shown in the formula I, the sulfonyl chloride shown in the formula II, the photocatalyst and the alkali is 1: 1-3: 0.02-0.1: 1-3; preferably, the molar ratio of the vinyl cyclopropane compound shown in the formula I, the sulfonyl chloride shown in the formula II, the photocatalyst and the base is 1:2:0.05: 2.

8. A method according to any one of claims 1-3, characterized in that: the post-processing comprises the following operations: after the reaction is finished, the reaction solution is filtered through a silica gel short column, ethyl acetate is washed, an organic phase is washed by saturated saline solution, an aqueous phase is extracted by ethyl acetate, the organic phase is combined, anhydrous Na2SO4 is dried, the solvent is removed through decompression and concentration to obtain a crude product, and then the crude product is purified through silica gel column chromatography separation (the elution solvent is n-hexane/ethyl acetate) to obtain the target product.

Technical Field

the application belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 1-sulfonylmethyl-3, 4-dihydronaphthalene.

Background

J. Org. Chem. J. Org. Chem.Dihydronaphthalene compounds are very important structural units in organic synthesis and pharmaceutical synthesis, and methods for effectively synthesizing the compounds have attracted great attention of organic synthesis chemists. The inventors have long sought to develop novel synthetic strategies for the synthesis of dihydronaphthalenes to introduce various different building blocks to construct novel reaction products and enrich the existing synthetic pathway (see 1) j. org. chem.201782147394-7401; 2) j, org, chem.20188384657-4664, 3) CN 106946817B; 4) CN 108129287A; 5) CN109651210A, etc.).

Over the past few decades, the introduction of sulfur-containing building blocks, particularly sulfonyl groups, into organic molecules has attracted a great deal of attention from chemists. Among common sulfonyl sources, sulfonyl chloride is a cheap, abundant and easily available sulfonyl source, and the inventors have reported a synthesis strategy for constructing 2-sulfonyl 3, 4-dihydronaphthalene compounds by the reaction of sulfonyl chloride with methylene cyclopropane compounds under photocatalytic conditions (see 6) CN 109705001A):

however, the prior art also widely reports that Arylsulfonyl Chlorides can be used as a source of aryl radicals to participate in the construction of a series of organic synthetic Reactions under Visible Light mediated conditions (see 7) derived cyclations of 1, 6-enzymes with aryl radicals by Using Visible-Light phosphor Catalysts, Jin-heng Li et al, Angewandte Chemie International Edition, 2013; 8) Reusable Visible Light phosphor Catalysts, catalyst substituted C (sp3) -H functional/Carbocyclics reaction, Jin-heng Li et al, Synlett, 2012, etc.).

Chem. Commun., The Aiwen Lei group of topics reported a visible light-induced, oxidant-free oxidative cross-coupling reaction to construct allylsulfone compounds from olefins and sulfinic acids, where the following reactions (see 9) chem. commu., 2016, 52, 10407-10410) were disclosed in the study of the mechanism:

The inventor conducts long-term intensive research and experimental investigation, and provides a visible light mediated C-C sigma-bond sulfonylation/arylation reaction, and a 1-sulfonylmethyl-substituted 3, 4-dihydronaphthalene compound is synthesized by the reaction of vinyl cyclopropane compounds and sulfonyl chloride.

Disclosure of Invention

the invention aims to enrich synthesis routes for preparing 1-sulfonylmethyl-substituted 3, 4-dihydronaphthalene compounds, and provides a novel method for synthesizing 1-sulfonylmethyl-substituted 3, 4-dihydronaphthalene compounds by reacting vinyl cyclopropane compounds and sulfonyl chloride under the mediation of visible light. The method has the advantages of mild reaction conditions, wide substrate application range, high yield of target products and the like.

The invention provides a novel method for preparing 1-sulfonyl methyl substituted 3, 4-dihydronaphthalene compounds,

。

the method comprises the following steps:

The method comprises the steps of sequentially adding vinyl cyclopropane compounds shown in the formula I, sulfonyl chloride shown in the formula II, photocatalyst, alkali and an organic solvent into a Schlenk tube sealing reactor, then protecting the reactor with an inert atmosphere, placing the reactor in an oil bath kettle at 90-110 ℃ under the illumination condition, stirring and reacting for 12-36 hours, detecting the reaction completely through TLC and/or GC-MS, and carrying out post-treatment to obtain target products shown in the formula III.

Wherein, in the formula I and the formula III, the structural units represent aryl of C6-C20 and heteroaryl of C3-C20; r1 represents one or more substituents on the structural unit, each R1 substituent being independently selected from hydrogen, C1-C20 alkyl, C1-C20 alkoxy, C6-C20 aryl, nitro, halogen, -CN;

In the formulas II and III, R2 is selected from C1-C20 alkyl, substituted or unsubstituted C6-C20 aryl, and C3-C20 heteroaryl; and wherein the substituents in the "substituted or unsubstituted" are selected from halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, nitro, C1-C6 acyl, -CN.

Preferably, in the formula I and the formula III, the structural units represent aryl of C6-C14 and heteroaryl of C3-C12; r1 represents one or more substituents on the structural unit, each R1 substituent being independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C6-C14 aryl, nitro, halogen, -CN;

in the formulas II and III, R2 is selected from C2-C12 alkyl, substituted or unsubstituted C6-C14 aryl, and C3-C12 heteroaryl; and wherein the substituents in the "substituted or unsubstituted" are selected from halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, nitro, C1-C6 acyl, -CN.

Most preferably, the compound of formula I is selected from compounds having the following structure:

。

The compound of formula II is selected from compounds having the following structure:

。

According to the method, the photocatalyst is any one of Ru (bpy)3Cl2, Ir (ppy)3, Eosin Y and Na2-Eosin Y; preferably, the photocatalyst is selected from Ru (bpy)3Cl 2.

According to the method of the invention, the base is selected from any one of 2, 6-lutidine, K2CO3, Na2CO3, Cs2CO3, pyridine or triethylamine; preferably, the base is selected from 2, 6-lutidine.

The method according to the present invention, wherein the organic solvent is selected from any one of 1, 4-dioxane, THF, DMF, DMSO, toluene, and acetonitrile; preferably, the organic solvent is selected from 1, 4-dioxane.

In the aforementioned method according to the present invention, as for the "inert atmosphere", it is understood by those skilled in the art that the "inert atmosphere" is understood to be an atmosphere inert to the reaction, and is not mechanically considered to be an inert gas. The "inert atmosphere" may be an argon atmosphere, a nitrogen atmosphere, or the like. Preferably, the "inert atmosphere" is an argon atmosphere.

According to the aforementioned method of the present invention, the heteroatom in the heteroaryl group having the carbon number in any part may be selected from any one or more of N, S and O; as concrete examples of the heteroaryl group having the above-mentioned number of carbon atoms, thienyl, furyl, pyridyl, pyrrolyl and the like can be cited.

According to the method of the present invention, the illumination condition can be provided by a 5W blue LED lamp, a 3W blue LED lamp, a 36W fluorescent lamp or a 5W green LED lamp. Preferably a 5W blue LED lamp.

According to the method of the invention, the reaction time of the reaction is preferably 24 hours, and the reaction temperature is preferably 100 ℃.

According to the method, the molar ratio of the vinyl cyclopropane compound shown in the formula I, the sulfonyl chloride shown in the formula II, the photocatalyst and the alkali is 1: 1-3: 0.02-0.1: 1-3; preferably, the molar ratio of the vinyl cyclopropane compound shown in the formula I, the sulfonyl chloride shown in the formula II, the photocatalyst and the base is 1:2:0.05: 2.

the method according to the present invention, wherein the post-processing comprises the following operations: after the reaction is finished, the reaction solution is filtered through a silica gel short column, ethyl acetate is washed, an organic phase is washed by saturated saline solution, an aqueous phase is extracted by ethyl acetate, the organic phase is combined, anhydrous Na2SO4 is dried, the solvent is removed through decompression and concentration to obtain a crude product, and then the crude product is purified through silica gel column chromatography separation (the elution solvent is n-hexane/ethyl acetate) to obtain the target product.

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

1) The invention reports a new method for synthesizing a 1-sulfonyl methyl substituted 3, 4-dihydronaphthalene compound by the reaction of a vinyl cyclopropane compound and sulfonyl chloride mediated by visible light for the first time;

2) the synthesis strategy of the invention has the advantages of easily available reaction raw material sources, mild reaction conditions, simple operation, recyclable catalyst, wide reaction substrate application range, high target product yield and the like.

Detailed Description

the present invention is described in further detail below with reference to specific examples: