CN115821292A - Gamma-sulfonyl internal etherification derivative and preparation method thereof - Google Patents
Gamma-sulfonyl internal etherification derivative and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to the field of synthesis of internal ether compounds, and particularly relates to a gamma-sulfonyl internal etherification derivative and a preparation method thereof. The gamma-sulfonyl internal etherification derivative is obtained by electrifying sulfonyl hydrazine compounds and aryl enol in an electrolyte solution for electrochemical reaction. The invention takes sulfonyl hydrazide compounds and aryl enol as starting raw materials, and realizes electrocatalysis one-pot two-component oxidation coupling reaction to prepare the gamma-sulfonyl lactonization derivative. Compared with the existing synthesis method, the new synthesis method provided by the invention does not need to use additional oxidant and catalyst, has the advantages of simple and easily-obtained raw materials, short reaction route, convenient experimental operation, low production cost and mild reaction conditions, and the prepared target product is easy to purify, has good yield and high product purity, is a brand-new synthesis method which is more economic, more environment-friendly and simpler and milder in reaction conditions, and has wide application prospect.
Description
Technical Field
The invention belongs to the field of synthesis of internal ether compounds, and particularly relates to a gamma-sulfonyl internal etherification derivative and a preparation method thereof.
Background
The oxygen-containing heterocyclic derivative is a key skeleton structure widely existing in natural products and drug molecules, and a plurality of compounds containing the oxygen-containing heterocyclic structure have good biological activity and important pharmaceutical value, such as a compound A, neohesperidin, which is a flavonoid compound existing in cucurbitaceae plants in a large amount and has antioxidant and anti-inflammatory effects. The synthesis of oxygen-containing heterocyclic compounds such as lactons has also once been a focus of research by organic synthesis workers.
However, in the prior art, both the aryl sulfonylation and the internal etherification processes often involve the use of a toxic and expensive transition metal catalyst or a photocatalyst with an exogenous oxidant, and the preparation process has the disadvantages of high temperature, long reaction time and the like. Therefore, the development of a greener and milder synthesis method of sulfonated lacton can better meet the needs of actual industrial production.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a preparation method of a gamma-sulfonyl lactonization derivative, which specifically adopts the following technical scheme:
a preparation method of a gamma-sulfonyl internal etherification derivative comprises the following steps: electrifying the sulfonyl hydrazide compound and aryl enol in an electrolyte solution to carry out electrochemical reaction to obtain the gamma-sulfonyl internal etherification derivative, wherein the reaction temperature is 30-70 ℃.
The invention takes sulfonyl hydrazide compounds and aryl enol as starting materials, and two molecules of oxidative coupling and cyclization are realized through electrochemistry to construct the gamma-sulfonyl internal etherified derivative. The raw material sulfonyl hydrazide can be used as both a sulfonylation reagent and a nitrogen source to participate in the reaction, and the generated byproducts are only nitrogen and water. Compared with the existing synthesis method of sulfonated lacton, the novel synthesis method provided by the invention does not need to use additional oxidant and catalyst, has the advantages of simple and easily-obtained raw materials, short reaction route, convenient experimental operation, low production cost, non-harsh reaction conditions (operable under normal pressure, simple required equipment), easy purification of the prepared target product, good yield and high product purity, and is a brand-new synthesis method which is more economic, more environment-friendly and has simpler and more mild reaction conditions.
In the solution system of the invention, the solvent is acetonitrile, dichloromethane, tetrahydrofuran or methanol. During the reaction, the TLC spot plate is used for monitoring the reaction (generally the reaction is carried out for 3-6 hours), after the reaction is finished, ethyl acetate is used for extraction (3-5 times), and after an organic layer is concentrated, the ethyl acetate and petroleum ether eluent column chromatography is used for separation to obtain the target product. In the electrochemical reaction, the electrode anode is carbon felt or carbon rod, and the electrode cathode is one of platinum sheet, iron sheet, stainless steel sheet and zinc sheet.
In some preferred embodiments, the structure of the sulfonyl hydrazide compound in the preparation method is as follows:
r is selected from C 1 -C 5 Alkyl, phenyl containing a single electron donating or electron withdrawing group (such as methylphenyl substituted at different positions, methoxyphenyl and phenyl substituted with different halogens), and fused ring groups. More preferably, the sulfonyl hydrazide compound is benzenesulfonyl hydrazide, 4-isopropylbenzenesulfonyl hydrazide, p-trifluoromethyl benzenesulfonyl hydrazide or sulfonyl hydrazide. The benzene sulfonyl hydrazide has low oxidation potential, is easy to form stable free radicals under electrochemical conditions and has high reaction activity, so the benzene sulfonyl hydrazide is the optimal choice for the invention.
In some preferred embodiments, the structure of the aryl enol in the above preparation process is as follows:
it was found experimentally that the yield of n =1,2 would be more advantageous. More preferably, the aryl enol is 4-phenylpent-4-enol, 4- (p-tolyl) pent-4-enol or 4- (furan-3-yl) pent-4-en-1-ol.
The reaction formula of the preparation method is as follows:
in some preferred embodiments, the electrolyte in the above preparation method is one of tetrabutylammonium fluoroborate, tetrabutylammonium perchlorate, lithium perchlorate and tetrabutylammonium iodide. It has been found experimentally that the most preferred electrolyte is tetrabutylammonium perchlorate.
In some preferred embodiments, the molar ratio of the sulfonyl hydrazide compound to the aryl enol in the above preparation method is (1-2): 1. wherein the preferred molar ratio is 1.5.
In some preferred embodiments, the current applied in the above preparation method is 5mA-12mA. Wherein the preferred current is 10mA.
In some preferred embodiments, the reaction in the above preparation process is carried out under a nitrogen atmosphere. This leads to a decrease in yield in an air atmosphere.
The invention has the beneficial effects that: the invention takes sulfonyl hydrazide compounds and aryl enol as starting raw materials, and realizes electrocatalysis one-pot two-component oxidation coupling reaction to prepare the gamma-sulfonyl lactonization derivative. Compared with the existing synthesis method, the new synthesis method provided by the invention does not need to use an additional catalyst, has the advantages of simple and easily-obtained raw materials, short reaction route, low production cost, non-harsh reaction conditions, easy purification of the prepared target product, good yield and high product purity, is a brand-new synthesis method which is more economic, more environment-friendly, simpler and milder in reaction conditions, and has wide application prospect.
Detailed Description
The concept and technical effects of the present invention will be clearly and completely described in the following embodiments to fully understand the objects, aspects and effects of the present invention.
Example 1:
a preparation method of a gamma-sulfonyl internal etherification derivative comprises the following steps:
adding 79.2mg of benzenesulfonyl hydrazide, 102.6mg of tetrabutylammonium perchlorate and a stirrer into a clean 50mL three-necked bottle, then plugging the bottle mouth by using a soft rubber plug with an electrode (a carbon felt is used as an anode, a platinum sheet is used as a cathode), connecting a branch pipe with a balloon filled with nitrogen, ventilating a reaction tube for three times, finally adding 48.6mg of 4-phenylpent-4-enol and 8mL of acetonitrile solvent into an injector, reacting for 5 hours under the condition of 60 ℃ and 10mA current, and monitoring by a TLC point plate; after the reaction is finished, adding water into the reaction solution, extracting the reaction solution for 3 times by using ethyl acetate, concentrating an organic layer, and separating the organic layer by using column chromatography to obtain a pure target product, wherein the pure target product is yellow oily, and the yield is 76%.
Nuclear magnetic and infrared data were as follows: 1 H NMR(400MHz,CDCl 3 )δ7.75(d,J＝7.5Hz,2H),7.54(t,J＝7.4Hz,1H),7.43(t,J＝7.7Hz,2H),7.33–7.15(m,5H),3.94(q,J＝7.5Hz,1H),3.88–3.79(m,1H),3.68(q,J＝14.0Hz,2H),2.85–2.71(m,1H),2.37–2.24(m,1H),2.13–1.95(m,1H),1.85–1.71(m,1H)； 13 C NMR(101MHz,CDCl 3 )δ144.4,141.3,133.1,128.8,128.3,127.8,127.3,125.2,83.9,68.1,65.4,37.0,25.2；IR(KBr)
2972,2880,1447,1308,1148,1084,703,688,557cm -1 。
example 2:
a method for preparing a gamma-sulfonyl lactonization derivative, which is different from the method of example 1 in that: the experimental conditions such as the dosage of each raw material, the reaction temperature and the like are changed. The specific reaction process is as follows:
adding 80.2mg of 4-isopropylbenzenesulfonylhydrazide, 102.6mg of tetrabutylammonium perchlorate and a stirrer into a clean 50mL three-necked bottle, then plugging the bottle mouth by using a soft rubber plug with an electrode (a carbon felt is used as an anode and a platinum sheet is used as a cathode), connecting a branch pipe with a balloon filled with nitrogen, ventilating a reaction tube for three times, finally adding 48.6mg of 4-phenylpent-4-enol and 7mL of acetonitrile solvent into an injector, reacting for 4 hours under the conditions of 70 ℃ and 10mA current, and monitoring by TLC point plates; after the reaction is finished, adding water into the reaction solution, extracting the reaction solution for 3 times by using ethyl acetate, concentrating an organic layer, and separating the organic layer by using column chromatography to obtain a pure target product which is yellow oily and has the yield of 73%.
Nuclear magnetic and infrared data were as follows: 1 H NMR(400MHz,CDCl 3 )δ7.64(d,J＝8.3Hz,2H),7.31–7.14(m,7H),3.97(q,J＝7.4Hz,1H),3.90–3.78(m,1H),3.66(q,J＝14.0Hz,2H),2.94(p,J＝6.9Hz,1H),2.82–2.70(m,1H),2.36–2.26(m,1H),2.12–1.99(m,1H),1.83–1.73(m,1H),1.24(d,J＝6.9Hz,6H)； 13 C NMR(101MHz,CDCl 3 )δ154.6,144.3,138.6,128.2,127.9,127.2,126.9,125.2,83.9,68.0,65.5,37.1,34.2,25.2,23.6；IR(KBr)
2962,2874,1597,1315,1151,1055,702,567,532cm -1 。
example 3:
a method for preparing a gamma-sulfonyl lactonization derivative, which is different from the method of example 1 in that: the experimental conditions such as the dosage of each raw material and the reaction electrolyte are changed. The specific reaction process is as follows:
adding 108.2mg of p-trifluoromethyl benzenesulfonyl hydrazide, 31.8mg of lithium perchlorate and a stirrer into a clean 50mL three-necked bottle, then plugging the bottle mouth by using a soft rubber plug with an electrode (a carbon felt is used as an anode, a platinum sheet is used as a cathode), connecting a branch pipe with a balloon filled with nitrogen, ventilating a reaction tube for three times, finally adding 48.6mg of 4-phenylpent-4-enol and 6mL of methanol solvent into an injector, reacting for 5 hours at 65 ℃ under the condition that the current is 10mA, and monitoring by a TLC plate; after the reaction is finished, adding water into the reaction solution, extracting the reaction solution for 3 times by using ethyl acetate, concentrating an organic layer, and carrying out column chromatography separation to obtain a pure target product, namely a white solid with the yield of 70%.
Nuclear magnetic and infrared data were as follows: 1 H NMR(400MHz,CDCl 3 )δ7.83(d,J＝8.1Hz,2H),7.65(d,J＝8.2Hz,2H),7.25–7.10(m,5H),3.97–3.89(m,1H),3.84(td,J＝8.1,5.6Hz,1H),3.75(q,J＝14.0Hz,2H),2.67(dt,J＝12.5,8.2Hz,1H),2.34–2.24(m,1H),2.09–1.98(m,1H),1.85–1.71(m,1H)； 13 C NMR(101MHz,CDCl 3 )δ144.5,143.7,134.6(d,J＝30.3Hz),128.5,128.3,127.4,125.7(q,J＝4.1Hz),125.1,123.1(d,J＝273.1Hz),83.6,68.2,65.5,37.7,25.1； 19 F NMR(376MHz,CDCl 3 )δ-63.2ppm；IR(KBr)
2969,1404,1324,1170,1143,1062,837,767,700,539cm -1 。
example 4:
a method for preparing a gamma-sulfonyl lactonization derivative, which is different from the method of example 1 in that: the experimental conditions such as the dosage of each raw material and the reaction temperature are changed. The specific reaction process is as follows:
adding 79.2mg benzenesulfonyl hydrazide, 110.7mg tetrabutylammonium iodide and a stirrer into a clean 50mL three-necked bottle, then plugging the bottle mouth by using a soft rubber plug with an electrode (a carbon felt is used as an anode and a platinum sheet is used as a cathode), connecting a balloon filled with nitrogen by using a branch pipe, ventilating the reaction tube for three times, finally adding 52.8mg 4- (p-tolyl) pent-4-enol and 6mL acetonitrile solvent by using an injector, reacting for 5 hours under the conditions of 40 ℃ and 10mA current, and monitoring by using a TLC point plate; after the reaction is finished, adding water into the reaction solution, extracting the reaction solution for 3 times by using ethyl acetate, concentrating an organic layer, and carrying out column chromatography separation to obtain a pure target product, namely a colorless liquid with the yield of 72%.
Nuclear magnetic and infrared data were as follows: 1 H NMR(400MHz,CDCl 3 )δ7.74(d,J＝7.2Hz,2H),7.58–7.49(m,1H),7.42(t,J＝7.7Hz,2H),7.20–7.13(m,2H),7.03(d,J＝7.9Hz,2H),3.91(q,J＝7.5Hz,1H),3.81(td,J＝8.0,5.6Hz,1H),3.66(d,J＝2.7Hz,2H),2.74(dt,J＝12.5,8.3Hz,1H),2.35–2.22(m,4H),2.10–1.97(m,1H),1.83–1.72(m,1H)； 13 C NMR(101MH z,CDCl 3 )δ141.4,141.3,136.9,132.9,128.9,128.7,127.8,125.1,83.8,68.0,65.6,36.9,25.2,20.9；IR(KBr)
2924,2878,1447,1308,1148,1084,818,582,529cm -1 。
example 5:
a method for preparing a gamma-sulfonyl lactonization derivative, which is different from the method of example 1 in that: the amount of each raw material and the experimental conditions such as reaction electrode are changed. The specific reaction process is as follows:
adding 52.8mg of sulfonyl hydrazide, 73.8mg of tetrabutylammonium iodide and a stirrer into a clean 50mL three-necked bottle, then plugging the bottle mouth by using a soft rubber plug with an electrode (a carbon rod is used as an anode, a platinum sheet is used as a cathode), connecting a balloon filled with nitrogen by a branch pipe, ventilating a reaction tube for three times, finally adding 30.4mg of 4- (furan-3-yl) pent-4-en-1-ol and 6mL of dichloromethane solvent by using an injector, reacting for 4 hours under the condition of 40 ℃ and 10mA current, and monitoring by using a TLC point plate; after the reaction is finished, adding water into the reaction solution, extracting the reaction solution for 3 times by using ethyl acetate, concentrating an organic layer, and carrying out column chromatography separation to obtain a pure target product, namely a black liquid with the yield of 78%.
Nuclear magnetic and infrared data were as follows: 1 H NMR(400MHz,CDCl 3 )δ7.78(d,J＝7.8Hz,2H),7.57(t,J＝7.3Hz,1H),7.46(t,J＝7.7Hz,2H),7.23(d,J＝19.4Hz,2H),6.15(s,1H),3.90–3.74(m,2H),3.64(d,J＝3.3Hz,2H),2.63–2.53(m,1H),2.29–2.19(m,1H),2.07–2.00(m,1H),1.91(dt,J＝12.3,7.8Hz,1H)； 13 C NMR(101MHz,CDCl 3 )δ143.3,141.0,139.3,133.2,129.1,128.8,127.8,108.4,79.5,67.7,64.8,36.3,25.4；IR(KBr)
2973,2881,1447,1307,1149,1024,874,688,565,526。
the above description is only a preferred embodiment of the present invention, and the present invention is not limited to the above embodiment, and the present invention shall fall within the protection scope of the present invention as long as the technical effects of the present invention are achieved by the same means. The invention is capable of other modifications and variations in its technical solution and/or its implementation, within the scope of protection of the invention.
Claims (10)
1. A preparation method of a gamma-sulfonyl internal etherification derivative is characterized by comprising the following steps: electrifying the sulfonyl hydrazide compound and aryl enol in an electrolyte solution to carry out electrochemical reaction to obtain the gamma-sulfonyl internal etherification derivative, wherein the reaction temperature is 30-70 ℃.
2. The preparation method according to claim 1, wherein the sulfonyl hydrazide compound has the following structure:
3. The method according to claim 2, wherein the sulfonyl hydrazide compound is benzenesulfonyl hydrazide, 4-isopropylbenzenesulfonyl hydrazide, p-trifluoromethylbenzenesulfonyl hydrazide or sulfonyl hydrazide.
4. The process according to claim 1, wherein the structure of the aryl enol is as follows:
5. The process according to claim 4, wherein the aryl enol is 4-phenylpent-4-enol, 4- (p-tolyl) pent-4-enol or 4- (furan-3-yl) pent-4-en-1-ol.
6. The method according to claim 1, wherein the electrolyte is one of tetrabutylammonium fluoroborate, tetrabutylammonium perchlorate, lithium perchlorate and tetrabutylammonium iodide.
7. The method according to claim 1, wherein the molar ratio of the sulfonyl hydrazide compound to the aryl enol is (1-2): 1.
8. the method according to claim 1, wherein the current to be applied is 5mA-12mA.
9. The method according to claim 1, wherein the reaction is carried out under a nitrogen atmosphere.
10. A γ -sulfonyllactonized derivative, characterized by being produced by the production method according to any one of claims 1 to 9.
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