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CN-117534596-B - Method for preparing beta-sulfonyl methyl acrylate compound

CN117534596BCN 117534596 BCN117534596 BCN 117534596BCN-117534596-B

Abstract

The invention relates to a method for preparing beta-sulfonyl methyl acrylate compounds. In particular to a one-pot method for preparing the terminal alkyne and the organic sodium sulfinate under the condition of oxidation in a carbon monoxide atmosphere. The invention starts from a substrate which is widely and commercially available, namely terminal alkyne and organic sodium sulfinate, and obtains a series of beta-sulfonyl methyl acrylate compounds through a free radical process under the conditions of oxidation and no need of transition metal catalysis.

Inventors

  • WU XIAOFENG
  • CHEN BO
  • YIN HAN
  • BAO ZHIPENG
  • KUAI CHANGSHENG

Assignees

  • 中国科学院大连化学物理研究所

Dates

Publication Date
20260512
Application Date
20220802

Claims (12)

  1. 1. A method for preparing beta-sulfonyl methyl acrylate compounds is characterized in that: The beta-sulfonyl methyl acrylate derivative 3 is produced by taking terminal alkyne 1 and organic sodium sulfinate 2 shown in the following formula as raw materials, wherein the reaction formula is as follows: ; R 1 is one of 3-thienyl, n-hexyl, phenyl or substituted phenyl, the substituent on the benzene ring of the substituted phenyl comprises one to five of methyl, tertiary butyl, fluorine atom, chlorine atom, bromine atom, methyl formate group and trifluoromethoxy, the number of the substituent is 1-5, R 2 is one of phenyl, 4-methylphenyl, 4-fluorophenyl, 4-chlorophenyl, ethyl and methyl, and the specific operation steps are as follows: The method comprises the steps of reacting in a high-pressure reaction kettle, weighing an oxidant, iodized salt, terminal alkyne 1, organic sodium sulfinate 2 and a solvent containing methanol, placing the oxidant, the terminal alkyne 1, the organic sodium sulfinate 2 and the solvent containing methanol in the high-pressure reaction kettle, replacing the atmosphere in the reaction kettle with a carbon monoxide atmosphere under 10-60 atm, reacting at 90-150 ℃ for 10.0-24.0 hours, and separating to obtain the beta-sulfonyl methyl acrylate compound 3 after the reaction is finished, wherein the oxidant is one of potassium persulfate, sodium persulfate, ammonium persulfate and potassium peroxymonosulfonate.
  2. 2. A method according to claim 1, characterized in that: The substituent groups on the benzene ring of the substituted phenyl comprise 1-2 of methyl, tertiary butyl, fluorine atom, chlorine atom, bromine atom, methyl formate group and trifluoromethoxy, the number of the substituent groups is 1-2, the atmosphere in the reaction kettle is replaced by carbon monoxide atmosphere under 10-60 atmospheric pressure, and the reaction is carried out at 130-140 ℃ for 20.0-24.0 hours.
  3. 3. A process according to claim 1, wherein the molar ratio of terminal alkyne 1 to organic sodium sulfinate 2 compound is from 1:1.0 to 3.0.
  4. 4. A process according to claim 3, wherein the molar ratio of terminal alkyne 1 to organic sodium sulfinate 2 compound is from 1:1.5 to 2.5.
  5. 5. A process according to claim 3, wherein the molar ratio of terminal alkyne 1 to organic sodium sulfinate 2 compound is 1:2.0.
  6. 6. The method according to claim 1, wherein the methanol-containing solvent is a mixture of methanol and other solvents, the other solvents are one or more of 1, 2-dichloroethane, tetrahydrofuran, dimethyl sulfoxide, 1, 4-dioxane, acetonitrile and water, the volume ratio of the methanol to the other solvents is 0.5-5:1, and the amount of the methanol-containing solvent is 1.0-5.0 ml per 0.2 mmol of the terminal alkyne 1.
  7. 7. The process according to claim 6, wherein the methanol-containing solvent is a mixture of methanol and other solvents, the other solvents being water, the volume ratio of methanol to water being 3-5:1, and the amount of methanol-containing solvent being 2.0 ml of solvent per 0.2 mmol of terminal alkyne 1.
  8. 8. The method of claim 7, wherein the volume ratio of methanol to water is 3.5-4:1.
  9. 9. The method of claim 1, wherein the oxidizing agent is sodium persulfate and the amount of the oxidizing agent is 2 to 4 times the number of moles of the terminal alkyne 1.
  10. 10. The method of claim 9, wherein the amount of the oxidizing agent is 2.2 to 2.5 times the number of moles of the terminal alkyne 1.
  11. 11. The method according to claim 1, wherein the iodine-containing salt is one of potassium iodide, sodium iodide, lithium iodide, calcium iodide and tetrabutylammonium iodide, and the iodine-containing salt is used in an amount of 1 to 3 times the number of moles of terminal alkyne 1.
  12. 12. The method of claim 11, wherein the iodine-containing salt is potassium iodide and the iodine-containing salt is used in an amount of 1.1 to 1.5 times the number of moles of terminal alkyne 1.

Description

Method for preparing beta-sulfonyl methyl acrylate compound Technical Field The invention relates to a method for synthesizing beta-sulfonyl methyl acrylate compounds. Background Beta-sulfonyl methyl acrylate is a very important chemical structural fragment because it is widely found in various natural products and modern drugs and has good biological activity. Furthermore, it is also a very important and valuable fragment in organic synthesis. The synthesis of methyl β -sulfonyl acrylate has been generally achieved by a multi-step reaction and requires the use of air-labile butyl lithium reagents. In recent years, the difunctional carbonylation reaction to produce polyfunctional carbonyl-containing compounds has become a promising approach. Compared with the prior synthesis method of the beta-sulfonyl methyl acrylate compound, the method develops a difunctional carbonylation reaction of alkyne to synthesize the beta-sulfonyl methyl acrylate in one step. By using simple and easy-to-prepare terminal alkyne and organic sodium sulfinate, we can synthesize beta-sulfonyl methyl acrylate with a wide substrate in one step. In summary, a process is described herein for obtaining a series of beta-methyl sulfonyl acrylate compounds via a free radical process under oxidizing conditions and without the need for transition metal catalysis. Disclosure of Invention The invention aims to provide a method for synthesizing a beta-sulfonyl methyl acrylate derivative. Reaction equation 1. Synthesis of a beta-sulfonylmethyl acrylate derivative wherein the wavy line represents a trans-or cis-structure linkage; The specific operation steps are as follows (reaction equation 1): the preparation method comprises the steps of reacting in a high-pressure reaction kettle, weighing oxidant, iodized salt, terminal alkyne 1 and organic sodium sulfinate 2, reacting at 90-150 ℃ and preferably 130 ℃ in a carbon monoxide atmosphere under 10-60 atm, reacting for 10.0-24.0 hours and preferably 20.0 hours, and separating to obtain the beta-sulfonyl methyl acrylate compound 3 after the reaction is finished. The molar ratio of the terminal alkyne 1 to the organic sodium sulfinate 2 compound is 1:1.0-3.0, preferably 1:1.5-2.5, more preferably 1:2.0. The carbon monoxide gas pressure is 10 to 60 atmospheres, preferably 40 to 45 atmospheres. The solvent is one or more of 1, 2-dichloroethane, tetrahydrofuran, dimethyl sulfoxide, 1, 4-dioxane, acetonitrile, methanol, and methanol-water mixture, preferably methanol-water mixture (the volume ratio of methanol to water is 0.5-5:1, preferably 3-5:1, more preferably 3.5-4:1), and the solvent is used in an amount of 1.0-5.0 ml, preferably 2.0 ml, per 0.2 mmol of the terminal alkyne 1. The oxidant is one or more than two of potassium persulfate, sodium persulfate and ammonium persulfate, preferably sodium persulfate, and the amount of the oxidant is 2-4 times, preferably 2.2-2.5 times, the mole number of the terminal alkyne 1. The iodine-containing salt is one or more of potassium iodide, sodium iodide, lithium iodide, calcium iodide, tetrabutylammonium iodide, and simple substance iodine, preferably potassium iodide, and the dosage of the iodine-containing salt is 1-3 times, preferably 1.1-1.5 times of the mole number of terminal alkyne 1. The invention starts from a substrate which is widely and commercially available, namely terminal alkyne and organic sodium sulfinate, and obtains a series of beta-sulfonyl methyl acrylate compounds through a free radical process under the conditions of oxidation and no need of transition metal catalysis. The invention has the following advantages: firstly, the reaction does not need to use metal reagents such as n-butyllithium and the like to synthesize the beta-sulfonyl methyl acrylate derivative, thereby greatly expanding the substrate range. Second, all the compounds including aryl terminal alkyne, alkyl terminal alkyne, sodium aryl sulfinate and sodium alkyl sulfinate can be converted in the reaction, so that the applicability of the reaction is widened. Thirdly, the beta-sulfonyl methyl acrylate is prepared by a one-pot method in one step, and the reaction steps are reduced. Detailed Description For a better understanding of the present invention, it is illustrated by the following examples. The starting materials and results for examples 1-14 are shown in Table 1. TABLE 1 reaction results of different substituted terminal alkynes 1 and organic sodium sulfinate 2 Example 1 Firstly adding phenylacetylene 1a (0.2 mmol), sodium phenylsulfinate 2a (0.4 mmol), sodium persulfate (0.44 mmol) and potassium iodide (0.22 mmol) into a 4ml glass vial, adding magneton, adding 2.0 ml solvent with a methanol/water volume ratio of 4:1, tightly covering the vial mouth by using a rubber bottle cap, inserting one end of a syringe needle tip into the vial through the bottle cap, enabling the vial to be communicated with the outside through the needle tip, putting the reaction vial into t