CN111777534B - Alkynyl sulfone compound and preparation method and application thereof - Google Patents
Alkynyl sulfone compound and preparation method and application thereof Download PDFInfo
- Publication number
- CN111777534B CN111777534B CN202010756061.6A CN202010756061A CN111777534B CN 111777534 B CN111777534 B CN 111777534B CN 202010756061 A CN202010756061 A CN 202010756061A CN 111777534 B CN111777534 B CN 111777534B
- Authority
- CN
- China
- Prior art keywords
- compound
- sulfone compound
- alkynyl sulfone
- alkynyl
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/14—Sulfones; Sulfoxides having sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/06—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C317/18—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Electrochemistry (AREA)
- Materials Engineering (AREA)
- Metallurgy (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of chemical synthesis, and particularly discloses an alkynyl sulfone compound and a preparation method and application thereof. The alkynyl sulfone compound provided by the invention takes an alkyne compound, a sodium sulfinate compound, potassium iodide, water and an organic solvent as raw materials, the alkynyl sulfone compound can be prepared by electrolysis, the alkynyl sulfone compound can be synthesized under the mild condition without a metal catalyst, the conditions of high temperature, oxygen enrichment, constant pressure and the like are not required, the reaction condition is not harsh, the steps are simple, the multi-step reaction is not required, the synthesis steps are simplified, and the problems that the existing alkynyl sulfone compound has harsh conditions and complicated steps in the preparation are solved; the preparation method of the alkynyl sulfone compound is simple to operate, high in yield and high in economic applicability.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to an alkynyl sulfone compound and a preparation method and application thereof.
Background
The alkynyl sulfone compound (alkynyl sulfone) is a compound modified by sulfone containing an unsaturated C-C bond, can be converted into a key intermediate of other heterocyclic compounds, has various biological activities and photoconductivity, and has wide application in the fields of life sciences, organic synthesis, drug synthesis and the like.
Currently, there are many reports on the synthesis of alkynyl sulfones, and efficient oxidative cross-coupling reactions involving terminal alkynes remain challenging. However, the preparation methods of alkynyl sulfones in the prior art usually require the use of alkyl halides or alkynes as substrates and the use of excess amounts of oxidizing agents and metal cleaving agents. The part is to oxidize alkynyl sulfide by peroxide, and synthesize by oxidation selenium removal method or dehydrohalogenation method. And the other method adopts sulfonyl hydrazide and alkyne for electrochemical synthesis.
However, the above method for synthesizing an alkynyl sulfone compound has the following disadvantages in practical use: the existing alkynyl sulfone compound needs conditions of high temperature, oxygen enrichment, constant pressure and the like in preparation, so that the conditions are harsh, and the steps are complicated. Therefore, there is an urgent need to develop a more efficient synthesis method, which can realize synthesis under mild conditions without metal catalyst and simplify the synthesis steps.
Disclosure of Invention
The embodiment of the invention aims to provide an alkynyl sulfone compound, and aims to solve the problems that the existing alkynyl sulfone compound in the background technology has harsh conditions and complicated steps in preparation.
In order to achieve the above purpose, the embodiments of the present invention provide the following technical solutions:
an alkynyl sulfone compound comprises the following raw materials: alkyne compounds, sodium sulfinate compounds, potassium iodide (KI) and water (H)2O) and an organic solvent, wherein the mol ratio of the alkyne compound to the sodium sulfinate compound is 1: 1-6.
As a further scheme of the invention: the mol ratio of the alkyne compound to the sodium sulfinate compound is 1: 2-4.
Preferably, the mol ratio of the alkyne compound to the sodium sulfinate compound is 1: 3.
As a still further scheme of the invention: the alkynyl sulfone compound is prepared by mixing an alkyne compound, a sodium sulfinate compound, potassium iodide, water and an organic solvent and electrolyzing.
As a still further scheme of the invention: the electrolysis condition is that the electrolysis is carried out for 1 to 24 hours at room temperature under the constant current of 5 to 15 mA.
As a still further scheme of the invention: the organic solvent is acetonitrile (CH)3CN), ethyl acetate or acetone.
As a still further scheme of the invention: in the raw material, the addition amount of the alkyne compound and the organic solvent is 3-4mL of the organic solvent for each millimole of the alkyne compound.
Preferably, the alkyne compound and the organic solvent are added in the starting material in an amount of 3.3mL of acetonitrile per millimole of alkyne compound.
As a still further scheme of the invention: in the raw material, the mol ratio of the alkyne compound to the potassium iodide is 1: 0.5-1.5.
As a still further scheme of the invention: in the raw material, the addition amount of the alkyne compound and the water is 0.03-0.06mL of water per millimole of alkyne compound.
Preferably, the acetylenic compound and the water are added in the starting material in an amount of 0.033mL of water per millimole of acetylenic compound.
As a still further scheme of the invention: the alkyne compound is an alkyne compound containing phenyl and/or substituted phenyl. Specifically, the alkyne compound includes any one or more of a phenyl alkyne compound or a substituted phenyl alkyne compound.
As a still further scheme of the invention: the sodium sulfinate compound is a sodium sulfinate compound containing phenyl and/or substituted phenyl. Specifically, the sodium sulfinate compound comprises any one or more of sodium benzene sulfinate or sodium p-methyl benzene sulfinate.
Another object of the embodiments of the present invention is to provide a method for preparing an alkynyl sulfone compound, and in particular, to a method for preparing an alkynyl sulfone compound by diaphragm-free electrochemical synthesis using sodium sulfinate and alkyne as raw materials, wherein the method for preparing an alkynyl sulfone compound comprises the following steps: mixing an alkyne compound, a sodium sulfinate compound, potassium iodide, water and an organic solvent, and then carrying out electrolysis and separation to obtain a target product, namely the alkyne sulfone compound.
As a still further scheme of the invention: the electrolysis condition is that the electrolysis is carried out for 1 to 24 hours at room temperature under the constant current of 5 to 15 mA.
Preferably, the preparation method of the alkynyl sulfone compound is that the alkyne compound, the sodium sulfinate compound, the potassium iodide, the water and the acetonitrile are added into an undivided three-neck flask (25mL) which is dried in an oven and is provided with a stirring rod in advance and mixed to obtain a mixture, the three-neck flask is provided with a platinum electrode as an anode and a cathode, the mixture is stirred and electrolyzed at constant current of 10mA at room temperature for 7 hours, after the reaction is finished, the solvent is removed by rotary evaporation through a rotary evaporator, petroleum ether and ethyl acetate are used as eluent, and the pure product is obtained by flash chromatography on silica gel.
As a still further scheme of the invention: the rotary steaming has the rotation speed of 100-200rpm, the temperature of 25-30 ℃, the vacuum degree of 0.08-0.12Mpa and the treatment time of 3-5 min.
As a still further scheme of the invention: in the preparation method of the alkynyl sulfone compound, the chromatography is performed by adopting 100-mesh 300-mesh column chromatography silica gel, the developing agent of the column chromatography is petroleum ether and ethyl acetate, and the petroleum ether: the volume ratio of the ethyl acetate is 15-30: 1.
Another object of the embodiments of the present invention is to provide an alkynyl sulfone compound prepared by the above preparation method of an alkynyl sulfone compound.
As a still further scheme of the invention: the structure of the alkynyl sulfone compound is shown as a formula I:
R in formula I2And R1Are independent groups, and the carbon number is 1-12.
Further, R2And R1Are each independentlyA vertical substituent, in particular, R2And R1Can be independently selected from aldehyde group, carbonyl group, ester group, nitro group, carboxyl group, substituted or unsubstituted C1-C12 alkyl group, substituted or unsubstituted C1-C12 aryl group, substituted or unsubstituted C1-C12 cycloalkyl group, substituted or unsubstituted C1-C12 alkoxy group, substituted or unsubstituted C1-C12 alkylamino group, substituted or unsubstituted C1-C12 alkylene group, substituted or unsubstituted C1-C12 alkynyl group, substituted or unsubstituted C1-C12 heterocyclic group, substituted or unsubstituted C1-C12 condensed ring group, or substituted or unsubstituted C1-C12 spiro ring group.
Of course, it should be noted that the alkynyl sulfones compounds are not limited to the structure shown in formula I, R2And R1The substituent groups may be other substituents having 1 to 12 carbon atoms, and are not limited thereto.
Another object of the embodiments of the present invention is to provide an application of the above alkynyl sulfone compound in the preparation of a pharmaceutical intermediate and/or the preparation of a basic skeleton of a drug.
Another object of the embodiment of the present invention is to provide an application of the preparation method of the alkynyl sulfone compound in organic synthesis.
As a still further scheme of the invention: the application can be the application of the alkynyl sulfone compound and the derivative thereof in organic synthesis or drug synthesis, or the application can be the application of the alkynyl sulfone compound as a raw material for preparing drugs or organic materials, or the application can be the application of the alkynyl sulfone compound as a basic skeleton of various natural products such as drugs after subsequent derivation.
Compared with the prior art, the invention has the beneficial effects that:
the alkynyl sulfone compound provided by the invention takes an alkyne compound, a sodium sulfinate compound, potassium iodide, water and an organic solvent as raw materials, the alkynyl sulfone compound can be prepared by electrolysis, the alkynyl sulfone compound can be synthesized under the mild condition without a metal catalyst, the conditions of high temperature, oxygen enrichment, constant pressure and the like are not required, the reaction condition is not harsh, the steps are simple, the multi-step reaction is not required, the synthesis steps are simplified, and the problems that the existing alkynyl sulfone compound has harsh conditions and complicated steps in the preparation are solved; the preparation method of the alkynyl sulfone compound is simple to operate, is a method for electrochemically synthesizing the alkynyl sulfone compound without a diaphragm, is particularly suitable for synthesizing some medicaments because the whole reaction is carried out in an organic solvent system, fundamentally eliminates the problems of metal residue and the like, and has high yield and higher economic applicability.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without inventive exercise. Wherein:
fig. 1 is a H-spectrum of a nuclear magnetic spectrum of the alkynyl sulfone compound prepared in example 1 of the present invention.
Fig. 2 is a H-spectrum of a nuclear magnetic spectrum of the alkynyl sulfone compound prepared in example 2 of the present invention.
Fig. 3 is a H-spectrum of a nuclear magnetic spectrum of the alkynyl sulfone compound prepared in example 3 of the present invention.
Fig. 4 is a H-spectrum of a nuclear magnetic spectrum of the alkynyl sulfone compound prepared in example 4 of the present invention.
Detailed Description
The invention is described in further detail below with reference to the figures and 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 those skilled in the art can easily and easily make a similar generalization without departing from the spirit of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below. All falling within the scope of the present invention.
Furthermore, reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one implementation of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.
Example 1
An alkynyl sulfone compound, which has a specific structural formula as follows:
in this embodiment, the specific synthesis steps of the alkynyl sulfone compound with the above structure are as follows:
a three-necked, undivided flask (25mL) equipped with a stir bar, which had been oven-dried in advance, was charged with phenylacetylene (0.3mmol), sodium p-toluenesulfinate (0.9mmol), KI (1.0 equivalent), and H2O (0.1mL) and CH3CN (10.0mL) is mixed to obtain a mixture, a three-neck flask is provided with a platinum electrode (1.0cm multiplied by 0.2mm) as an anode and a cathode, the mixture is stirred and electrolyzed at constant current of 10mA for 7h at room temperature, after the reaction is finished, a reaction system is transferred into a 25mL eggplant-shaped bottle, a Heidolph rotary evaporator (the rotating speed is 80-100rpm, the temperature is 38 ℃ and the vacuum degree is 0.1Mpa) is used for carrying out rotary evaporation treatment for 3min, the residue is subjected to column chromatography by using 200-mesh column chromatography silica gel (the developing agent of the column chromatography is petroleum ether and ethyl acetate, the volume ratio of the petroleum ether to the ethyl acetate is 20: 1), and a target compound (70.7mg, the yield is 92 percent and the purity is 98 percent by HPLC analysis) is separated to obtain the alkynyl sulfone compound with the structure.
In this example, a nuclear magnetic detection analysis is performed on the target compound obtained by separation, and a specific nuclear magnetic spectrum is shown in fig. 1, where fig. 1 is a nuclear magnetic spectrum H of the alkynyl sulfone compound prepared in example 1, and a specific nuclear magnetic spectrum analysis result is as follows:
1H NMR(600MHz，CDCl3)δ7.95(d，J＝8.4Hz，2H)，7.51(d，J＝7.1Hz，2H)，7.46(t，J＝7.5Hz，1H)，7.41-7.33(m，4H)，2.46(s，3H)。
referring to fig. 1 and the specific nmr spectrum analysis results, it can be seen that the product purity is very high in terms of nmr spectrum appearance, signal, noise, etc.
Example 2
An alkynyl sulfone compound, which has a specific structural formula as follows:
in this embodiment, the specific synthesis steps of the alkynyl sulfone compound with the above structure are as follows:
an oven-dried undivided three-necked flask (25mL) equipped with a stir bar was charged with p-methoxyphenylacetylene (0.3mmol), sodium p-toluenesulfinate (0.9mmol), KI (1.0 equivalent), H2O (0.1mL) and CH3CN (10.0mL) is mixed to obtain a mixture, a three-neck flask is provided with a platinum electrode (1.0cm multiplied by 0.2mm) as an anode and a cathode, the mixture is stirred and electrolyzed at constant current of 10mA for 7h at room temperature, after the reaction is finished, a reaction system is transferred into a 25mL eggplant-shaped bottle, a Heidolph rotary evaporator (the rotating speed is 80-100rpm, the temperature is 38 ℃ and the vacuum degree is 0.1Mpa) is used for carrying out rotary evaporation treatment for 3min, the residue is subjected to column chromatography by using 200-mesh column chromatography silica gel (the developing agent of the column chromatography is petroleum ether and ethyl acetate, the volume ratio of the petroleum ether to the ethyl acetate is 20: 1), and a target compound (60.6mg, the yield is 80 percent and the purity is 98 percent by HPLC) is obtained by separation, namely the alkynyl sulfone compound with the structure.
In this example, a nuclear magnetic detection analysis is performed on the target compound obtained by separation, and a specific nuclear magnetic spectrum is shown in fig. 2, where fig. 2 is a nuclear magnetic spectrum H spectrum of the alkynyl sulfone compound prepared in example 2, and a specific nuclear magnetic spectrum analysis result is as follows:
1H NMR(600MHz，CDCl3)δ7.94(d，J＝8.3Hz，2H)，7.44(d，J＝8.9Hz，2H)，7.37(d，J＝8.1Hz，2H)，6.85(d，J＝8.9Hz，2H)，3.81(s，3H)，2.45(s，3H)。
referring to fig. 2 and the specific nmr spectrum analysis results, it can be seen that the product purity is very high in terms of nmr spectrum appearance, signal, noise, etc.
Example 3
An alkynyl sulfone compound, which has a specific structural formula as follows:
in this embodiment, the specific synthesis steps of the alkynyl sulfone compound with the above structure are as follows:
a three-necked flask (25mL) with a stirrer rod, which was not separately opened and dried in an oven, was charged with phenylacetylene (0.3mmol), sodium p-tert-butylsulfinate (0.9mmol), KI (1.0 equivalent), and H2O (0.1mL) and CH3CN (10.0mL) is mixed to obtain a mixture, a three-neck flask is provided with a platinum electrode (1.0cm multiplied by 0.2mm) as an anode and a cathode, the mixture is stirred and electrolyzed at constant current of 10mA for 7h at room temperature, after the reaction is finished, a reaction system is transferred into a 25mL eggplant-shaped bottle, a Heidolph rotary evaporator (the rotating speed is 80-100rpm, the temperature is 38 ℃ and the vacuum degree is 0.1Mpa) is used for carrying out rotary evaporation treatment for 3min, the residue is subjected to column chromatography by using 200-mesh column chromatography silica gel (the developing agent of the column chromatography is petroleum ether and ethyl acetate, the volume ratio of the petroleum ether to the ethyl acetate is 20: 1), and a target compound (52.7mg, the yield is 59 percent and the purity is 98 percent by HPLC) is obtained through separation, namely the alkynyl sulfone compound with the structure.
In this example, a nuclear magnetic detection analysis is performed on the target compound obtained by separation, and a specific nuclear magnetic spectrum is shown in fig. 3, where fig. 3 is a nuclear magnetic spectrum H spectrum of the alkynyl sulfone compound prepared in example 3, and a specific nuclear magnetic spectrum analysis result is as follows:
1H NMR(600MHz，CDCl3)δ8.03(d，J＝8.7Hz，2H)，7.52(d，J＝8.6Hz，2H)，6.70(s，1H)，1.35(s，9H)。
referring to fig. 3 and the specific nmr spectrum analysis results, it can be seen that the product purity is very high in terms of nmr spectrum appearance, signal, noise, etc.
Example 4
An alkynyl sulfone compound, which has a specific structural formula as follows:
in this embodiment, the specific synthesis steps of the alkynyl sulfone compound with the above structure are as follows:
a dry, undivided three-necked flask (25mL) equipped with a stir bar was charged with phenylacetylene (0.3mmol), sodium p-bromophenylsulfinate (0.9mmol), KI (1.0 equivalent), H2O (0.1mL) and CH3CN (10.0mL) is mixed to obtain a mixture, a three-neck flask is provided with a platinum electrode (1.0cm multiplied by 0.2mm) as an anode and a cathode, the mixture is stirred and electrolyzed at constant current of 10mA for 7h at room temperature, after the reaction is finished, a reaction system is transferred into a 25mL eggplant-shaped bottle, a Heidolph rotary evaporator (the rotating speed is 80-100rpm, the temperature is 38 ℃ and the vacuum degree is 0.1Mpa) is used for carrying out rotary evaporation treatment for 3min, the residue is subjected to column chromatography by using 200-mesh column chromatography silica gel (the developing agent of the column chromatography is petroleum ether and ethyl acetate, the volume ratio of the petroleum ether to the ethyl acetate is 20: 1), and a target compound (60.7mg, the yield is 63 percent) is separated, and the purity is 98 percent through HPLC analysis, namely the alkynyl sulfone compound with the structure.
In this example, a nuclear magnetic detection analysis is performed on the target compound obtained by separation, and a specific nuclear magnetic spectrum is shown in fig. 4, where fig. 4 is a nuclear magnetic spectrum H of the alkynyl sulfone compound prepared in example 4, and a specific nuclear magnetic spectrum analysis result is as follows:
1H NMR(600MHz，CDCl3)δ8.07(d，J＝9.0Hz，2H)，6.97(d，J＝9.0Hz，2H)，6.67(s，1H)，3.89(s，3H)。
referring to fig. 4 and the specific nmr spectrum analysis results, it can be seen that the product purity is very high in terms of nmr spectrum appearance, signal, noise, etc.
Example 5
Same as example 2 except that the acetonitrile was replaced with ethyl acetate, compared to example 2.
Example 6
Same as example 2 except that the acetonitrile was replaced with acetone, compared to example 2.
Example 7
In one example, phenylacetylene (0.3mmol), sodium p-toluenesulfinate (0.9mmol), KI (1.0 equivalent), H, were added to an undivided three-necked flask (25mL) equipped with a stir bar, oven dried beforehand, at room temperature2Mixing O (0.1mL) and an organic solvent (10.0mL) to obtain a mixture, wherein the organic solvent is acetonitrile, a three-neck flask is provided with a platinum electrode (1.0cm multiplied by 0.2mm) as an anode and a cathode, stirring and electrolyzing the mixture at room temperature for 7 hours at a constant current of 10mA, transferring a reaction system into a 25mL eggplant-shaped bottle after the reaction is finished, carrying out rotary evaporation treatment for 3 minutes by using a Heidolph rotary evaporator (the rotating speed is 80-100rpm, the temperature is 38 ℃ and the vacuum degree is 0.1MPa), carrying out column chromatography on residues by using 200-mesh column chromatography silica gel (the developing agent of the column chromatography is petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is 20: 1), separating to obtain a target compound, and measuring the mass of the prepared alkynyl sulfone compound to calculate the yield.
Example 8
Same as example 7 except that the acetonitrile was replaced with ethyl acetate, compared to example 7.
Example 9
Same as example 7 except that the acetonitrile was replaced with chloroform, compared with example 7.
Example 10
Same as example 7 except that the acetonitrile was replaced with acetone, compared with example 7.
Example 11
Same as example 7 except that the acetonitrile was replaced with dimethyl sulfoxide, compared with example 7.
Example 12
The alkynyl sulfones compounds correspondingly obtained in examples 7 to 11 are respectively subjected to mass measurement to calculate the yield, and then the influence of different solvents on the yield can be discussed, and the specific influence results of different solvents on the yield are shown in table 1.
Table 1 influence of different solvents on the yield results table
| Serial number | The solvent used | Yield (%) |
| 1 | Acetonitrile | 92 |
| 2 | Ethyl acetate | 8 |
| 3 | Trichloromethane | 0 |
| 4 | Acetone (II) | 36 |
| 5 | Dimethyl sulfoxide | 0 |
In this example, it can be seen from table 1 that different solvents have different effects on the yield of the preparation method of the alkynyl sulfone compound, wherein the yield corresponding to acetonitrile is 92%, which is the best reaction solvent, and the above solvents are all commercial products.
Example 13
Same as example 3 except that the acetonitrile was replaced with ethyl acetate, compared to example 3.
Example 14
Same as example 3 except that the acetonitrile was replaced with acetone, compared to example 3.
Example 15
In one embodiment, the influence of different current levels on the yield is discussed with reference to the preparation method of the alkynyl sulfone compound in example 7, specifically, the preparation method of the alkynyl sulfone compound in example 7, in which the constant current stirring electrolysis with 10mA for 7h is replaced by the constant current stirring electrolysis with 5mA for 10h and the constant current stirring electrolysis with 15mA for 4h, the mass of the prepared corresponding alkynyl sulfone compound is measured to calculate the yield, and the specific influence results of different reaction temperatures on the yield are shown in table 2.
TABLE 2 influence of different current levels on yield
| Serial number | Current (mA) | Yield (%) |
| 1 | 5 | 60 |
| 2 | 10 | 93 |
| 3 | 15 | 73 |
In this example, as can be seen from table 2, different current magnitudes have different influences on the yield of the preparation method of the alkynyl sulfone compound, wherein the yield is 93% corresponding to 7h of electrolysis with 10mA constant current stirring.
Example 16
The procedure of example 7 was repeated, except that the electrolysis was carried out at a constant current of 10mA for 7 hours, and the electrolysis was carried out at a constant current of 5mA for 1 hour.
Example 17
The procedure of example 7 was repeated, except that the electrolysis was carried out at a constant current of 10mA for 7 hours, and the electrolysis was carried out at a constant current of 5mA for 24 hours, as compared with example 7.
Example 18
The procedure of example 7 was repeated, except that the electrolysis was carried out at a constant current of 10mA for 7 hours, and the electrolysis was carried out at a constant current of 12mA for 12 hours, as compared with example 7.
Example 19
The same procedure as in example 7 was repeated, except that the amount of sodium p-toluenesulfinate to be added was changed to 0.3mmol as compared with example 7.
Example 20
The same procedure as in example 7 was repeated, except that the amount of sodium p-toluenesulfinate to be added was changed to 0.6mmol as compared with example 7.
Example 21
The same procedure as in example 7 was repeated, except that the amount of sodium p-toluenesulfinate to be added was changed to 1.2mmol as compared with example 7.
Example 22
The same procedure as in example 7 was repeated, except that the amount of sodium p-toluenesulfinate to be added was changed to 1.8mmol as compared with example 7.
Example 23
Compared with example 7, except that the addition amount of phenylacetylene is replaced by 0.3mmol, the addition amount of sodium p-toluenesulfinate is replaced by 0.6mmol, the addition amount of KI is replaced by 0.15mmol, and H is2The amount of O added was changed to 0.09mL, and the amount of acetonitrile added was changed to 9mL, which was the same as in example 7.
Example 24
Compared with example 7, except that the addition amount of phenylacetylene is replaced by 0.3mmol, the addition amount of sodium p-toluenesulfinate is replaced by 1.2mmol, the addition amount of KI is replaced by 0.45mmol, and H is added2The amount of O added was changed to 0.2mL, and the amount of acetonitrile added was changed to 12mL, but the same procedures as in example 7 were repeated.
Example 25
The same procedure as in example 7 was repeated, except that the rotary evaporation treatment was carried out for 3 minutes using a Heidolph rotary evaporator (rotation speed: 80rpm, temperature: 25 ℃ C., vacuum: 0.08MPa), in comparison with example 7.
Example 26
The same procedure as in example 7 was repeated, except that the rotary evaporation treatment was carried out for 5 minutes using a Heidolph rotary evaporator (rotation speed: 200rpm, temperature: 30 ℃ C., vacuum: 0.12MPa), in comparison with example 7.
The alkynyl sulfone compound provided by the invention can be prepared by taking an alkyne compound, a sodium sulfinate compound, potassium iodide, water and an organic solvent as raw materials through electrolysis, can be synthesized under the mild condition without a metal catalyst, does not need conditions such as high temperature, oxygen enrichment, constant pressure and the like, has mild reaction conditions, simple steps, does not need multi-step reaction, simplifies the synthesis steps, and solves the problems of harsh conditions and complex steps existing in the preparation of the existing alkynyl sulfone compound; the preparation method of the alkynyl sulfone compound provided by the invention is a preparation method for electrochemically synthesizing the alkynyl sulfone compound by sodium sulfite and alkyne without diaphragms, mainly generates C-S and activation of C-H bonds thereof, the whole reaction does not need metal catalysis, is carried out in an organic solvent system, is particularly suitable for synthesis of some medicines, fundamentally eliminates the problems of metal residue and the like, has higher economic applicability, is simple to operate, has high yield, has purity of more than 98%, mild conditions and wide substrate range, can be suitable for simple substrates, and can modify complex natural products by the method.
It should be noted that, compared with the traditional synthesis method, the method of the invention has mild conditions and wide substrate range, so that not only simple substrates can be applicable, but also complex natural products can be modified by the method, and the developed alkynyl sulfone compounds are popular intermediates, can also be subsequently derived into basic frameworks of various natural products such as medicines and the like, and particularly have wide market prospects in the pharmaceutical industry.
It should be noted that the above-mentioned embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, which should be covered by the claims of the present invention.
Claims (5)
1. The preparation method of the alkynyl sulfone compound is characterized by comprising the following steps: mixing an alkyne compound, a sodium sulfinate compound, potassium iodide, water and an organic solvent to obtain a mixture, wherein the molar ratio of the alkyne compound to the sodium sulfinate compound is 1: 1-6, electrolyzing the mixture at room temperature under the condition of stirring and electrolyzing at room temperature for 1-24 hours at a constant current of 5-15mA, removing the solvent by rotary evaporation after the reaction is finished, and carrying out chromatographic separation on silica gel by using quick chromatography by using petroleum ether and ethyl acetate as eluent to obtain the alkynyl sulfone compound, wherein the alkyne compound is phenylacetylene or p-methoxybenzene acetylene, and the sodium sulfinate compound is sodium p-toluenesulfinate, sodium p-tert-butylphenylidenete or sodium p-bromobenzenesulfonate.
2. The method for preparing alkynyl sulfone compound of claim 1, wherein the molar ratio of alkyne compound to sodium sulfinate compound is 1: 2-4.
3. The preparation method of alkynyl sulfone compound of claim 1, wherein the organic solvent is any one of acetonitrile, ethyl acetate or acetone.
4. The preparation method of alkynyl sulfone compound of claim 1, wherein the addition amount of alkyne compound and organic solvent is 3-4mL of organic solvent for each millimole of alkyne compound, and the addition amount of alkyne compound and water is 0.03-0.06mL of water for each millimole of alkyne compound.
5. The method for preparing an alkynyl sulfone compound according to claim 1, wherein the molar ratio of the alkyne compound to the potassium iodide is 1: 0.5-1.5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010756061.6A CN111777534B (en) | 2020-07-30 | 2020-07-30 | Alkynyl sulfone compound and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010756061.6A CN111777534B (en) | 2020-07-30 | 2020-07-30 | Alkynyl sulfone compound and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111777534A CN111777534A (en) | 2020-10-16 |
| CN111777534B true CN111777534B (en) | 2022-04-12 |
Family
ID=72765207
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010756061.6A Active CN111777534B (en) | 2020-07-30 | 2020-07-30 | Alkynyl sulfone compound and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111777534B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112575343A (en) * | 2020-11-16 | 2021-03-30 | 上海应用技术大学 | Electrochemical synthesis method of beta-iodoalkenyl sulfone compound |
| CN115385831B (en) * | 2022-08-31 | 2023-11-10 | 浙江工业大学 | Method for preparing alkyne sulfone compound by oxidation of selenium-containing catalytic system |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111118529B (en) * | 2019-12-16 | 2021-03-26 | 南京林业大学 | Method for synthesizing alpha, alpha-dibromo ketone compound by membrane-free electrochemical oxidation of dihalogenated alkyne |
| CN111139494B (en) * | 2020-01-09 | 2021-07-02 | 广西师范大学 | Method for synthesizing alkyne sulfone compound from terminal alkyne and sulfonyl hydrazide under electrochemical condition |
-
2020
- 2020-07-30 CN CN202010756061.6A patent/CN111777534B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN111777534A (en) | 2020-10-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111777534B (en) | Alkynyl sulfone compound and preparation method and application thereof | |
| CN111118529B (en) | Method for synthesizing alpha, alpha-dibromo ketone compound by membrane-free electrochemical oxidation of dihalogenated alkyne | |
| CN108101733B (en) | Method for preparing polyaryl substituted naphthalene derivative by ruthenium catalysis reaction of fluoroarylone and tolane | |
| CN110627693B (en) | Allyl sulfone compound and preparation method and application thereof | |
| CN111705329B (en) | Electrochemical synthesis method of 5-arylthio uracil compound | |
| CN112126942A (en) | Method for realizing secondary arylamine N-N coupling by using electrochemical reaction | |
| CN112795943A (en) | Electrochemical synthesis method of 3, 4-dibromomaleimide | |
| CN109384789B (en) | Synthesis method of indolocazaheptatomic ring catalyzed by monovalent silver | |
| CN113881956A (en) | Preparation method of benzyl isocyanate compound | |
| CN112301370A (en) | Electrochemical synthesis method of 1, 3-dimethyl-3-difluoroethyl-2-oxindole compound | |
| CN111118530B (en) | Preparation method of chlorinated alkyne compound by electrochemical oxidation in diaphragm-free electrolytic cell | |
| Murphy | Efficient synthesis of 5, 6-diacetoxyindole: a stable eumelanin precursor | |
| FI72508C (en) | Process for the preparation of n-propylacetonitrile derivatives. | |
| Yu et al. | Regioselective electrochemical radical cascade cyclization of internal alkynes to selenated and trifluoromethylated dihydropyran | |
| CN113957463A (en) | Method for synthesizing dibenzosuberone derivative through free radical serial cyclization under electrooxidation condition | |
| CN106946758A (en) | A kind of synthetic method of 3 (trifluoroacetyl) indole derivativeses | |
| Zeng et al. | A facile electrochemical synthesis of caffeic acid derivatives in the presence of acetylacetone or methyl acetoacetate in aqueous medium | |
| JP3738225B2 (en) | Novel chiral copper catalyst and method for producing N-acylated amino acid derivative using the same | |
| CN115305490A (en) | Method for synthesizing fluoroalkyl substituted dibenzosuberone compound by electrooxidation | |
| CN110590717B (en) | Polysubstituted ketene imine and synthetic method thereof | |
| CN115785087B (en) | Synthesis method of monovalent gold catalyzed 1H-pyrido [4,3-b ] indole skeleton compound | |
| CN114478449B (en) | Polysubstituted selenium-containing dihydroisobenzofuran derivative and preparation method thereof | |
| CN113563164B (en) | Preparation method of alkynone compound | |
| EP3459947B1 (en) | Novel chiral phase-transfer catalyst, and method for preparing alpha-amino acid by using the same | |
| CN108586406B (en) | Preparation method of 3-sulfonyl coumarin compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |