CN109020848B - (E) Synthesis method of-alkenyl sulfone compound - Google Patents
(E) Synthesis method of-alkenyl sulfone compound Download PDFInfo
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Abstract
The invention disclosesE) The synthesis method of the-alkenyl sulfone compound comprises the following steps: acetonitrile as solvent in SbCl3Catalytic, 30% H2O2Simultaneously oxidizing the 1, 2-alkylene oxide compound (IV) to generate in situβPeroxyalcohols (V), oxidation of KI in situ to give I2. In the presence of Cu (II) salts2Catalyzing the reaction of cinnamic acid compound (II) and sulfonyl hydrazine compound (III) with compound (V), and synthesizing (V) through decarboxylation and denitrificationE) -alkenyl sulfones (I). The invention has the advantages of easily obtained raw materials and peroxidation reagentβThe peroxy alcohol compound and the iodine are generated in situ, the method is safe and economical, and the iodine-containing compound can be recycled.
Description
Technical Field
The invention relates to the field of organic chemical synthesis, in particular toE) A method for synthesizing an alkenyl sulfone compound.
Background
(E) The-alkenyl sulfone compounds have many good biological activities and are often used as potent inhibitors of enzymatic processes, such as inhibitors of VCAM-1 expression, cysteine protease inhibitors, HIV-1 integrase inhibitors, and the like. Furthermore, (A) toE) The-alkenyl sulfone compound is used as an important organic structural block and has wide application in organic synthetic chemistry, for example, the alkenyl sulfone compound can be used as an acceptor of Michael addition reaction and also can be used as an important raw material of D-A reaction. Li group reported that CuI or Cu/Fe cooperated with di-tert-butyl peroxide (DTBP) as catalyst, aromatic alkyne or aromatic alkynyl acid reacted with sulfonyl hydrazide at 100: (E) The yield of the alkenyl sulfone compounds is moderate (J. org. chem. 2015, 4697). Singh group reported DBU as a base at 40mol% I2And tert-butyl hydroperoxide (TBHP), reacting cinnamic acid compound with sulfonyl hydrazide at room temperatureE) The yield of the alkenyl sulfone compound is more than moderate (org. Lett. 2015, 2652). The methods all use peroxide with dangerous operation as raw materials, and are not suitable for large-scale production.
Disclosure of Invention
The object of the present invention is to provideE) The method for synthesizing the-alkenyl sulfone compound is characterized by comprising the following steps of: using acetonitrile asSolvent in SbCl3Catalytic, 30% H2O2Simultaneously oxidizing the 1, 2-alkylene oxide compound (IV) to generate in situβPeroxyalcohols (V), oxidation of KI in situ to give I2. In the presence of a Cu (II) salt, I2Catalyzing the reaction of cinnamic acid compound (II) and sulfonyl hydrazine compound (III) with compound (V), and synthesizing (V) through decarboxylation and denitrificationE) -alkenyl sulfones (I). The reaction formula is shown as the following formula:
in the formula, R1Independently selected from H, CH3, CN, OR, CF3One or more of alkyl, aryl, halogen groups are substituted at the ortho, para or meta position of the aromatic ring; r2Independently selected from the group consisting of alkyl, cycloalkyl, phenyl, variously substituted phenyl, aryl, variously substituted aryl; r3Independently selected from alkyl, substituted alkyl, cycloalkyl, phenyl, various substituted phenyl, aryl, various substituted aryl.
The inventionE) The method for synthesizing the-alkenyl sulfone compound is characterized in that the Cu (II) salt is CuSO4,Cu(OAc)2,CuCl2,CuBr2, Cu(NO3)2,Cu(CF3SO2)2,Cu(CF3CO2)2。
The inventionE) The method for synthesizing the-alkenyl sulfone compound is characterized in that the compound is shown in formula II, formula III, KI, H2O2Cu (II) salts and SbCl3The mass ratio of (A) to (B) is 1: 1: 0.4-0.5:6-7:2.5-3:0.5-0.6:0.1.
The inventionE) The synthesis method of the-alkenyl sulfone compound is characterized in that the peroxidation reagent isβPeroxyalcohols (V) consisting of 30% H2O2In SbCl3In situ generation of oxidized 1, 2-alkylene oxides (IV) in the presence of2From 30% H2O2Oxidized KI is generated in situ, and the method is safe and economical.
The inventionE) A method for synthesizing the-alkenyl sulfone compound, which is characterized in that the reaction for preparing the formula I by the formula II and the formula III is generated in situβPeroxy alcohol compounds (V) and I2Catalysis is completed through decarboxylation denitrification.
According to the inventionE) The method for synthesizing the-alkenyl sulfone compound is characterized in that the iodine-containing compound can be recycled.
Detailed Description
The following examples are intended to illustrate the invention in detail, but are not intended to limit the invention.
Example 1
In a reactor, 148mg (1mmol) of cinnamic acid, 206mg (1.2mmol) of benzenesulfonylhydrazide, 66.4mg (0.4mmol) of KI, 22.6mg (0.1mmol) of SbCl3，35.4mg (0.6mmol)CuSO4300mg (2.5mmol) of styrene oxide and 7mM CECN, stirred and then 689mg (6mmol) of 30% H were added2O2Reacting at room temperature for 1h, and adding 15mL of saturated NaHSO3Stirring the solution for 20min, evaporating MeCN under reduced pressure, adding 10mL of ethyl acetate and 10mLH2O, layering, extracting with ethyl acetate, drying, filtering, concentrating the filtrate, and purifying by silica gel column chromatography (petroleum ether/ethyl acetate 20: 1) to obtain (A), (B), (CE) - (benzenesulfonyl) vinylbenzene, yield 63.2%. mp 69-71 deg.C;1H NMR (400MHz, CDCl3) δ 7.95(d,J=15.2Hz, 1H),7.69(d,J=15.2Hz, 1H), 7.62(t,J=7.2Hz, 1H), 7.55(t,J=7.6Hz, 2H), 7.50-7.47(m, 2H), 7.42-7.37 (m, 3H), 6.87(d,J=15.2Hz, 1H)。
example 2
Into the reactor were added 178mg (1mmol) of 4-methoxycinnamic acid, 242mg (1.2mmol) of 4-methoxybenzenesulphonyl hydrazide, 66.4mg (0.4mmol) of KI, 22.6mg (0.1mmol) of SbCl3，73.2mg(0.55mmol)CuCl2216mg (3mmol) of 1, 2-epoxybutane and 7mM CECN, stirred and 804mg (7mmol) of 30% H were added2O2Reacting at room temperature for 1h, and adding 15mL of saturated NaHSO3Stirring the solution for 20min, evaporating MeCN under reduced pressure, adding 10mL of ethyl acetate and 10mLH2O, layering, extracting by ethyl acetate,drying, filtering, concentrating the filtrate, and purifying by silica gel column chromatography (petroleum ether/ethyl acetate 20: 1) to obtain (A), (B), (C), (E) -1-methoxy-4- (2- ((4-methoxyphenyl) sulfonyl) alkenyl) benzene, yield 74.7%.1H NMR (400MHz, CDCl3) δ 7.88(d,J=8.7Hz, 2H), 7.60(d,J=15.3Hz, 1H), 7.42(t,J=8.7Hz, 2H), 7.01(d,J=9.0Hz,2H), 6.90(d,J=8.7Hz, 2H), 6.72(d,J=15.6Hz,1H), 3.86(s, 3H), 3.83(s, 3H)。
Example 3
In a reactor, 162mg (1mmol) of 4-methylcinnamic acid, 233mg (1.2mmol) of n-octylsulfonylhydrazide, 66.4mg (0.4mmol) of KI, 22.6mg (0.1mmol) of SbCl were added3，108.6mg(0.6mmol)Cu(OAc)2174mg (3mmol) of 1, 2-epoxypropane and 7mM CECN are stirred, and 804mg (7mmol) of 30% H are added2O2Reacting at room temperature for 1h, and adding 15mL of saturated NaHSO3Stirring the solution for 20min, evaporating MeCN under reduced pressure, adding 10mL of ethyl acetate and 10mLH2O, layering, extracting with ethyl acetate, drying, filtering, concentrating the filtrate, and purifying by silica gel column chromatography (petroleum ether/ethyl acetate 20: 1) to obtain (A), (B), (CE) -1-methyl-4- (2- (octylsulfonyl) alkenyl) benzene, yield 73.9%.1H NMR (400MHz, CDCl3) δ 7.60(d,J=15.0Hz,1H), 7.43(d,J=7.8Hz, 2H), 7.24(d,J=7.8Hz, 2H), 6.79(d,J=15.6Hz, 1H), 3.06-2.91(m, 2H), 2.39(s, 3H), 1.84-1.75(m, 2H), 1.27-1.22(m, 8H), 8.07(t,J=6.9Hz, 3H)。
Example 4
Into the reactor, 182mg (1mmol) of 3-chlorocinnamic acid, 223mg (1.2mmol) of 4-tolylsulfonyl hydrazide, 66.4mg (0.4mmol) of KI, 22.6mg (0.1mmol) of SbCl were added3，93.5mg(0.5mmol)Cu(NO3)2385mg (2.5mmol) of 4-chlorostyrene and 7mL of MeCN which are stirred, then 689mg (6mmol) of 30% H are added2O2Reacting at room temperature for 1h, and adding 15mL of saturated NaHSO3Stirring the solution for 20min, evaporating MeCN under reduced pressure, adding 10mL of ethyl acetate and 10mLH2O, layering, extracting with ethyl acetate, drying, filtering, concentrating the filtrate, and purifying by silica gel column chromatography (petroleum ether/ethyl acetate 20: 1)Obtaining (a)E) -1-chloro-3- (2- (p-toluenesulfonyl) alkenyl) benzene, yield 67.4%.1H NMR (400MHz, CDCl3) δ 7.83(d,J=8.1Hz,2H),7.60(d,J=15.0Hz, 1H), 7.43-7.34(m,6H), 6.89(d,J=15.3Hz, 1H), 2.44(s,3H)。
Example 5
In a reactor, 162mg (1mmol) of 4-methylcinnamic acid, 209mg (1.1mmol) of 4-fluorophenylsulfonyl hydrazide, 66.4mg (0.4mmol) of KI, 22.6mg (0.1mmol) of SbCl were added3，159mg (0.55mmol)Cu(CF3CO2)2245mg (2.5mmol) of 1, 2-epoxycyclohexane and 7mL of MeCN are stirred and 689mg (6mmol) of 30% H are added2O2Reacting at room temperature for 1h, and adding 15mL of saturated NaHSO3Stirring the solution for 20min, evaporating MeCN under reduced pressure, adding 10mL of ethyl acetate and 10mLH2O, layering, extracting with ethyl acetate, drying, filtering, concentrating the filtrate, and purifying by silica gel column chromatography (petroleum ether/ethyl acetate 20: 1) to obtain (A), (B), (CE) -1-fluoro-4- ((4-tolyl) sulfonyl) alkenyl) benzene, yield 62.6%.1H NMR (400MHz, CDCl3)δ 7.98(m,2H),7.65(d,J=15.2Hz, 1H), 7.38(d,J=8.0Hz, 2H),7.24-7.19(m,4H),6.79(d,J=15.2Hz, 1H), 2.37(s, 3H)。
Claims (6)
1. (E) The method for synthesizing the-alkenyl sulfone compound is characterized by comprising the following steps of:
acetonitrile as solvent in SbCl3Catalytic, 30% H2O2Simultaneously oxidizing the 1, 2-alkylene oxide compound (IV) to generate in situβPeroxyalcohols (V), oxidation of KI in situ to give I2；
In the presence of a Cu (II) salt, I2Catalyzing the reaction of cinnamic acid compound (II) and sulfonyl hydrazine compound (III) with compound (V), and synthesizing (V) through decarboxylation and denitrificationE) -alkenyl sulfones (I);
the reaction formula is shown as the following formula:
in the formula, R1Independently selected from H, CH3, CN, CF3An aryl group; r2Independently selected from alkyl, cycloalkyl, phenyl; r3Independently selected from alkyl, substituted alkyl, cycloalkyl, phenyl.
2. (according to claim 1)E) The method for synthesizing the-alkenyl sulfone compound is characterized in that the Cu (II) salt is CuSO4, Cu(OAc)2, CuCl2, CuBr2, Cu(NO3)2, Cu(CF3SO2)2, Cu(CF3CO2)2。
3. (according to claim 1)E) The method for synthesizing the-alkenyl sulfone compound is characterized in that the compound is shown in formula II, formula III, KI, H2O2Cu (II) salts and SbCl3The mass ratio of (A) to (B) is 1: 1: 0.4-0.5:6-7:2.5-3:0.5:0.1.
4. (according to claim 1)E) The synthesis method of the-alkenyl sulfone compound is characterized in that the peroxidation reagent isβPeroxyalcohols (V) consisting of 30% H2O2In SbCl3In situ generation of oxidized 1, 2-alkylene oxides (IV) in the presence of2From 30% H2O2Oxidized KI is generated in situ.
5. (according to claim 1)E) A method for synthesizing the-alkenyl sulfone compound, which is characterized in that the reaction for preparing the formula I by the formula II and the formula III is carried out by in-situ generation of (V) and I2Catalysis is completed through decarboxylation denitrification.
6. (according to claim 1)E) The method for synthesizing the-alkenyl sulfone compound is characterized in that the iodine-containing compound can be recycled.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104961664A (en) * | 2015-07-21 | 2015-10-07 | 安徽理工大学 | Method for synthesizing E-alkenyl sulfone compound |
| CN107162943A (en) * | 2017-06-05 | 2017-09-15 | 同济大学 | A kind of (E) alkenyl sulfone compound and preparation method thereof |
| CN107417582A (en) * | 2017-05-25 | 2017-12-01 | 曲阜师范大学 | A kind of preparation method of E alkenyl sulfone compounds |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104961664A (en) * | 2015-07-21 | 2015-10-07 | 安徽理工大学 | Method for synthesizing E-alkenyl sulfone compound |
| CN107417582A (en) * | 2017-05-25 | 2017-12-01 | 曲阜师范大学 | A kind of preparation method of E alkenyl sulfone compounds |
| CN107162943A (en) * | 2017-06-05 | 2017-09-15 | 同济大学 | A kind of (E) alkenyl sulfone compound and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| A Direct Metal-Free Decarboxylative Sulfono Functionalization (DSF) of Cinnamic Acids to α,β-Unsaturated Phenyl Sulfones;Rahul Singh 等;《Organic Letters》;20150508;第17卷;第2656-2659页 * |
| Electrochemical Decarboxylative Sulfonylation of Cinnamic Acids with Aromatic Sulfonylhydrazides to Vinyl Sulfones;Yu Zhao 等;《J.Org.Chem.》;20170830;第82卷;第9655-9661页 * |
| 碘促进的砜基化反应研究进展;胡飞 等;《有机化学》;20150404;第35卷;第1848-1860页 * |
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