阅读说明：本技术 一种反式-3-苯硫基-γ-内酯的制备方法 (Preparation method of trans-3-thiophenyl-gamma-lactone ) 是由 刘永国 王皓 田红玉 梁森 杨绍祥 邱果 白宇辰 孙宝国 于 2021-09-27 设计创作，主要内容包括：本发明涉及结构式如下所示的反式-3-苯硫基-γ-内酯的制备方法：该方法步骤：室温条件下,向浓H-(2)SO-(4)中滴加浓HCl,产生的氯化氢气体通过浓H-(2)SO-(4)和变色硅胶干燥塔进行干燥处理,得到的无水HCl与甲基苯基亚砜在乙腈溶液中进行加热,油浴温度升至100℃时,将反式-3-烯酸加入,回流10小时,得到反式-3-苯硫基-γ-内酯,产率80-91％。(The invention relates to a preparation method of trans-3-thiophenyl-gamma-lactone with a structural formula shown as follows: the method comprises the following steps: at room temperature, the reaction solution is concentrated to H 2 SO 4 Concentrated HCl is dripped into the mixture, and the generated hydrogen chloride gas passes through concentrated H 2 SO 4 And drying the mixture in a allochroic silica gel drying tower to obtain anhydrous HCl and methyl phenyl sulfoxide, heating the anhydrous HCl and the methyl phenyl sulfoxide in an acetonitrile solution, adding the trans-3-olefine acid when the temperature of the oil bath is raised to 100 ℃, and refluxing for 10 hours to obtain the trans-3-thiophenyl-gamma-lactone with the yield of 80-91%.)

1. A process for preparing trans-3-phenylthio-gamma-lactone features that the anhydrous hydrogen chloride and methyl phenyl sulfoxide are used as initial raw materials, which are then reacted with 3-olefine acid to obtain trans-3-phenylthio-gamma-lactone,

Detailed Description

(1) Preparation of trans-3-thiophenyl-gamma-valerolactone

At room temperature, the reaction solution is concentrated to H₂SO₄Concentrated HCl is dripped into the mixture, and the generated hydrogen chloride gas passes through concentrated H₂SO₄And a allochroic silica gel drying tower for drying treatment, introducing into a three-neck flask containing 10mL of acetonitrile solution, absorbing about 0.14g of anhydrous HCl (3.75mmol, 0.75 equivalent) by acetonitrile, adding a solution of methyl phenyl sulfoxide (1.32mL, 11.25mmol) in acetonitrile (10mL), heating by using an oil bath kettle to 100 ℃, adding 0.50g of trans-3-pentenoic acid (5mmol), and refluxing for about 10 hours to complete the reaction of olefine acid by GC-MS tracking. After the reaction mixture was cooled to room temperature, acetonitrile was removed by rotary evaporation. Adding a proper amount of dichloromethane, washing with a saturated sodium bicarbonate solution and a saturated sodium chloride solution in sequence, then drying with anhydrous sodium sulfate, filtering, and removing the dichloromethane by rotary evaporation. The residue was purified by column chromatography (200-mesh 300-mesh silica gel; petroleum ether/ethyl acetate 50: 1) to give trans-3-phenylthio- γ -valerolactone 0.95g in 91% yield.¹H NMR(300MHz，CDCl₃)：δ＝7.32-7.24(m，5H，H-phenyl)，4.34(quin.，J＝6.4Hz，1H，H-C5)，3.42(td，J＝8.2，6.4Hz，1H，H-C4)，2.85(dd，J＝17.9，8.2Hz，1H，H-C3，A part of ABX)，2.44(dd，J＝17.9，8.2Hz，1H，H′-C3，B part of ABX)，1.29(d，J＝6.4Hz，3H，H-C6)。¹³C NMR(75MHz，CDCl₃)：δ＝174.0，132.9，131.7，129.2，128.2，81.2，48.0，35.7，19.3。

(2) Preparation of trans-3-thiophenyl-gamma-octalactone

At room temperature, the reaction solution is concentrated to H₂SO₄Concentrated HCl is dripped into the mixture, and the generated hydrogen chloride gas passes through concentrated H₂SO₄And allochroic silica gelThe drying column was dried, passed into a three-necked flask containing 10mL of acetonitrile, and after about 0.14g of anhydrous HCl (3.75mmol, 0.75 equivalent) was absorbed into acetonitrile, a solution of methylphenylsulfoxide (1.32mL, 11.25mmol) in acetonitrile (10mL) was added, followed by heating using an oil bath, and when the temperature was raised to 100 ℃, 0.75g of trans-3-octenoic acid (5mmol) was added, followed by GC-MS, and the olefinic acid reaction was completed under reflux for about 10 hours. After the reaction mixture was cooled to room temperature, acetonitrile was removed by rotary evaporation. Adding a proper amount of dichloromethane, washing with a saturated sodium bicarbonate solution and a saturated sodium chloride solution in sequence, then drying with anhydrous sodium sulfate, filtering, and removing the dichloromethane by rotary evaporation. The residue was purified by column chromatography (200-mesh 300-mesh silica gel; petroleum ether/ethyl acetate: 30: 1) to give trans-3-phenylthio- γ -octanolide 0.99g in 80% yield.¹H NMR(300MHz，CDCl₃)：δ＝7.42-7.27(m，5H，H-phenyl)，4.31(ddd，J＝8.2，6.1，4.5Hz，1H，H-C5)，3.59-3.52(m，1H，H-C4)，2.92(dd，J＝18.0，8.3Hz，1H，H-C3，A part of ABX)，2.53(dd，J＝18.0，7.4Hz，1H，H′-C3，B part of ABX)，1.81-1.17(m，6H，H-C6，H-C7 and H-C8)，0.87(t，J＝7.0Hz，3H，H-C9)。¹³C NMR(75MHz，CDCl₃)：δ＝174.2，133.1，131.9，129.2，128.3，84.8，46.4，35.8，33.5，27.2，22.0，13.6。

(3) Preparation of trans-3-thiophenyl-gamma-nonalactone

At room temperature, the reaction solution is concentrated to H₂SO₄Concentrated HCl is dripped into the mixture, and the generated hydrogen chloride gas passes through concentrated H₂SO₄And a allochroic silica gel drying tower for drying treatment, the obtained anhydrous HCl is introduced into a three-neck flask filled with 10mL of acetonitrile solution, about 0.14g of anhydrous HCl (3.75mmol, 0.75 equivalent) is absorbed by acetonitrile, then a solution of methyl phenyl sulfoxide (1.32mL, 11.25mmol) in acetonitrile (10mL) is added, then an oil bath pot is used for heating, when the temperature is raised to 100 ℃, 0.78g of trans-3-nonenoic acid (5mmol) is added, GC-MS tracking is carried out, and the olefine acid reaction is completely carried out under reflux for about 10 hours. After the reaction mixture was cooled to room temperature, acetonitrile was removed by rotary evaporation. Adding appropriate amount of dichloromethane, washing with saturated sodium bicarbonate solution and saturated sodium chloride solution sequentially, drying with anhydrous sodium sulfate, and filteringAnd removing dichloromethane by rotary evaporation. The residue was separated and purified by column chromatography (200-mesh 300-mesh silica gel; petroleum ether/ethyl acetate 50: 1) to give 1.1g of trans-3-phenylthio- γ -nonalactone in 83% yield.¹H NMR(300MHz，CDCl₃)：δ＝7.46-7.27(m，5H，H-phenyl)，4.32-4.28(m，1H，H-C5)，3.60-3.53(m，1H，H-C4)，2.92(dd，J＝18.0，8.3Hz，1H，H-C3，A part of ABX)，2.53(dd，J＝18.0，7.4Hz，1H，H′-C3，B part of ABX)，1.76-1.13(m，8H，H-C6，H-C7，H-C8 and H-C9)，0.86(t，J＝6.7Hz，3H，H-C10)。¹³C NMR(75MHz，CDCl₃)：δ＝174.1，133.0，131.8，129.1，128.2，84.7，46.3，35.7，33.7，31.0，24.7，22.2，13.7。