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CN-121991024-A - Synthesis method of 2-sulfolane

CN121991024ACN 121991024 ACN121991024 ACN 121991024ACN-121991024-A

Abstract

The invention relates to a method for synthesizing 2-sulfolane. The synthesis method comprises the following steps of mixing a compound I with an alkaline substance, and performing elimination reaction to obtain the 2-sulfolane. The invention carries out elimination reaction by simply stirring 3-substituted sulfolane in alkaline substances, and then prepares 2-sulfolane conveniently by simple separation and extraction. The method is simple to operate, has high selectivity, can specifically generate the target 2-sulfolane, and can not generate the byproduct 3-sulfolane, thereby greatly improving the synthesis yield and the purification efficiency. The synthesis method of 2-sulfolane provided by the invention has the characteristics of simple synthesis conditions, high selectivity, high yield and high purity.

Inventors

  • YANG BINGXIAO
  • SHEN YANBIN

Assignees

  • 中国科学院苏州纳米技术与纳米仿生研究所

Dates

Publication Date
20260508
Application Date
20260127

Claims (10)

  1. 1. A method for synthesizing 2-sulfolane, which is characterized by comprising the following steps: mixing the first compound with an alkaline substance, and performing elimination reaction to obtain the 2-sulfolane; the structure of the compound I is Z is any one of hydroxyl, nitro, cyano, F, cl, br or I.
  2. 2. The synthetic method according to claim 1, wherein the basic substance comprises any one or a combination of at least two of lithium aluminum hydride, calcium hydride, sodium borohydride, butyllithium, lithium metal, sodium metal, potassium metal, sodium ethoxide, potassium tert-butoxide, sodium amide, 1, 8-diazabicyclo undec-7-ene, 1, 5-diazabicyclo non-5-ene, diethylaminosulfur trifluoride, or bis (2-methoxyethyl) amino sulfur trifluoride.
  3. 3. The method according to claim 1 or 2, wherein the molar ratio of the compound I to the alkaline substance is 1.0 (0.2-5.0).
  4. 4. A synthetic method according to any one of claims 1 to 3 wherein the molar ratio of compound one to alkaline substance is 1.0 (1.0-3.0).
  5. 5. The method of any one of claims 1-4, wherein the elimination reaction has a reaction time of 3-72 h.
  6. 6. The method according to any one of claims 1 to 5, wherein the reaction temperature of the elimination reaction is-78 to 100 ℃.
  7. 7. The synthetic method of any one of claims 1 to 6 wherein the elimination reaction is carried out in a solvent.
  8. 8. The method of claim 7, wherein the solvent is an organic solvent.
  9. 9. The synthetic method according to claim 7 or 8, wherein the solvent comprises any one or a combination of at least two of n-heptane, n-hexane, dichloromethane, chloroform, tetrahydrofuran or 2-methyltetrahydrofuran.
  10. 10. The synthetic method of any one of claims 1 to 9 further comprising a post-treatment step after the elimination reaction; the post-treatment comprises the steps of adding sodium bicarbonate aqueous solution for quenching reaction, filtering, taking filtrate, steaming to remove solvent, pulping by using isopropanol and methyl tertiary butyl ether in sequence, filtering and drying to obtain 2-sulfolane, or adding sodium bicarbonate aqueous solution for quenching reaction, filtering, extracting filtrate by using an organic solvent, and distilling to obtain 2-sulfolane.

Description

Synthesis method of 2-sulfolane Technical Field The invention relates to the technical field of organic synthesis, in particular to a synthesis method of 2-sulfolane. Background Sulfolane is a highly reactive synthetic intermediate whose use is almost entirely due to the combined action of cyclic tension in the molecular structure and electron withdrawing sulfone groups, which makes it extremely prone to participate in a variety of important cycloaddition and ring opening reactions, such as diels-alder reactions and high molecular polymerization reactions. Therefore, it is very important in the synthesis of natural products and drug molecules. Depending on the position of the double bond on the ring, there are two isomers of sulfolane, namely 3-sulfolane and 2-sulfolane. Currently, 3-cyclobutene sulfone can be produced industrially in large quantities at low cost, but there is still a problem concerning efficient production of 2-cyclobutene sulfone. According to the molecular structure-activity relationship in chemistry, 2-sulfolane will be obviously different from 3-sulfolane in molecular performance, so that development of a synthetic method for conveniently preparing 2-sulfolane is needed. Currently, the methods for preparing 2-sulfolane in the laboratory are relatively limited and the yields are low. For example, a method for converting 3-sulfolane into 2-sulfolane has been reported in William J. Bailey, earl W. Cummins, journal of THE AMERICAN CHEMICAL Society, 1954, 76, 1932-1936, but the yield is only 41% and the separation and purification are complicated. Some patents (US 3293264A (1966), GB1057664A (1967) and PL 108316B 2 (1980)) report methods for preparing 2-cyclobutene sulfone using a precursor thermal cracking method, but the preparation process and isolation and purification remain very cumbersome. Therefore, how to provide a synthetic method for conveniently preparing high-purity 2-sulfolane is a technical problem to be solved in the field. Disclosure of Invention In order to solve the technical problems, the invention aims to provide a synthesis method of 2-sulfolane. The 3-substituted sulfolane is simply stirred in alkaline substances to carry out elimination reaction, and then the 2-sulfolane can be conveniently prepared through simple separation and extraction. The method is simple to operate, has high selectivity, can specifically generate the target 2-sulfolane, and can not generate the byproduct 3-sulfolane, thereby greatly improving the synthesis yield and the purification efficiency. The synthesis method of 2-sulfolane provided by the invention has the characteristics of simple synthesis conditions, high selectivity, high yield and high purity. To achieve the purpose, the invention adopts the following technical scheme: In a first aspect, the present invention provides a method for synthesizing 2-sulfolane, comprising the steps of: mixing the first compound with an alkaline substance, and performing elimination reaction to obtain the 2-sulfolane; the structure of the compound I is Z is any one of hydroxyl, nitro, cyano, F, cl, br or I. In the invention, the substituent group of the 3-substituted sulfolane is limited, so that the target product 2-sulfolane can be specifically generated, and the byproduct 3-sulfolane can not be generated. Preferably, the structural formula of the 2-sulfolane is。 Preferably, the basic substance comprises any one or a combination of at least two of lithium aluminum hydride, calcium hydride, sodium borohydride, butyllithium, lithium metal, sodium metal, potassium metal, sodium ethoxide, potassium tert-butoxide, sodium amide, 1, 8-diazabicycloundec-7-ene, 1, 5-diazabicyclon-5-ene, diethylaminosulfur trifluoride or bis (2-methoxyethyl) aminotrifluoride. In the present invention, the selectivity of the elimination reaction can be improved by selecting a specific alkaline substance. The alkaline substance has strong alkalinity, is easier to abstract hydrogen protons at ortho positions of 3-substituted sulfolane, and improves elimination reaction kinetics. Preferably, the molar ratio of the compound I to the alkaline substance is 1.0 (0.2-5.0), and can be 1.0:0.5, 1.0:1.0, 1.0:2.0, 1.0:3.0, 1.0:4.0, etc. Preferably, the molar ratio of the compound I to the alkaline substance is 1.0 (1.0-3.0), and can be 1.0:1.5, 1.0:1.8, 1.0:2.0, 1.0:2.5, 1.0:2.8 or the like. Preferably, the reaction time of the elimination reaction is 3-72 h, for example, 5h, 10 h, 20 h, 30 h, 40 h, 50 h or 60h, etc. Preferably, the reaction temperature of the elimination reaction is-78-100 ℃, for example, -50 ℃, -20 ℃,0 ℃,10 ℃, 20 ℃, 40 ℃,50 ℃ or 80 ℃ and the like. Preferably, the elimination reaction is carried out in a solvent. Preferably, the solvent is an organic solvent. Preferably, the solvent comprises any one or a combination of at least two of n-heptane, n-hexane, dichloromethane, chloroform, tetrahydrofuran or 2-methyltetrahydrofuran. Preferably, the method for post-treatment comp