CN108047118B - Synthetic method of 3-indolseleno alcohol organic compound - Google Patents
Synthetic method of 3-indolseleno alcohol organic compound Download PDFInfo
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Abstract
The invention discloses a synthesis method of a 3-indoneselenol organic compound, which is characterized in that an indole compound and cyclohexene oxide/cyclopentene oxide/1, 2-epoxybutane/methyl epoxypropane/3, 3-dimethyl epoxybutane/2-furan methyl glycidyl ether are used as reaction substrates, elemental selenium is used as a selenium source, water or an organic solvent is used as a reaction solvent, when water is used as the reaction solvent, a phase transfer catalyst tetrabutylammonium iodide is added into the water, and the 3-indoneselenol compound is obtained without transition metal catalysis under the action of inorganic base in a nitrogen atmosphere. The invention has the advantages that: the method can synthesize the 3-indoneselenol compound with high yield and high purity, has mild reaction conditions, wide range of reaction substrates, good tolerance of functional groups, simple post-treatment and simple and convenient operation, is suitable for large-scale industrial production, and provides a brand new synthesis route for the efficient and rapid synthesis of the compound.
Description
Technical Field
The invention relates to a synthetic method of an organic compound, in particular to a synthetic method of a 3-indoselenol organic compound, belonging to the technical field of organic compound synthesis.
Background
The 3-indoselenol organic compound is a class of asymmetric selenide compounds in selenium-containing compounds, has good physiological activity, and has important significance for synthesizing the 3-indoselenol compound by a new green synthesis method in organic synthesis and pharmaceutical chemistry by developing the selenium-containing compound through a new chemical structure.
In 2003, Venkataraman et al reported a method for preparing asymmetric diaryl monoselenide from aryl iodine and phenylselenol by using a CuI/2, 9-dimethyl-1, 10-phenanthroline catalytic system. The method adopts different bases according to the difference of electron effects on aryl iodine: when the substituent on iodobenzene is an electron-rich group, strong base t-BuONa is used; when the substituent on iodobenzene is an electron-withdrawing substituent, then weak base K is used2CO3. Although the method can prepare a series of asymmetric selenoethers, the phenylselenophenol has foul smell and high toxicity and is not suitable for being adopted.
In 2013, the Zeni topic group developed a method for preparing corresponding 3-organoselenoindole compounds and derivatives thereof from O-alkanylaniline and derivatives thereof and diaryl (alkyl) diselenide in a dichloromethane solution under the catalysis of ferric trichloride. The diselenide of the method completely reaches the product, the atom efficiency is high, the condition is mild, the economy is good, the energy consumption is low, and the synthesized 3-organic selenium indole compound can be used for preparing more complex indole derivatives through selenium lithium exchange, so that the method has potential use value. However, the method needs transition metal catalysis, simultaneously needs diselenide as a raw material, has unpleasant odor and does not meet the requirements of environmental protection by using a metal catalyst.
Disclosure of Invention
In order to solve the defects of the prior art, the invention aims to provide a method for synthesizing a 3-indoneseleno alcohol organic compound, which has mild conditions and simple and convenient operation, adopts elemental selenium as a selenium source and does not add any metal as a catalyst.
In order to achieve the above object, the present invention adopts the following technical solutions:
a synthetic method of a 3-indoneselenol organic compound is characterized in that an indole compound and cyclohexene oxide/cyclopentene oxide/1, 2-epoxybutane/methyl epoxypropane/3, 3-dimethyl epoxybutane/2-furan methyl glycidyl ether are used as reaction substrates, elemental selenium is used as a selenium source, water or an organic solvent is used as a reaction solvent, when water is used as the reaction solvent, a phase transfer catalyst tetrabutylammonium iodide is added into the water, and the 3-indoneselenol compound is obtained without transition metal catalysis under the action of inorganic base in a nitrogen atmosphere.
The synthesis method of the 3-indoselenol organic compound is characterized in that the simple substance selenium is selenium powder, and the molar ratio of the selenium powder to the indole is 1-3: 1.
The method for synthesizing the 3-indoselenol organic compound is characterized in that the organic solvent is at least one of tetrahydrofuran, 1, 4-dioxane, n-propanol and isopropanol.
The synthesis method of the 3-indoselenol organic compound is characterized in that the ratio of the water to the tetrabutylammonium iodide is 2mL:0.8 mmol.
The synthesis method of the 3-indoneselenol organic compound is characterized in that the inorganic base is at least one of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium phosphate, potassium phosphate, cesium carbonate, potassium hydroxide, sodium hydroxide and pyrrolidine.
The synthesis method of the 3-indoselenol organic compound is characterized in that the molar ratio of the use amount of the inorganic base to the use amount of the indole is 1-3: 1.
The synthesis method of the 3-indoselenol organic compound is characterized in that the reaction temperature is 20-60 ℃, and the reaction time is 6-16 h.
The synthesis method of the 3-indoselenol organic compound is characterized in that the reaction temperature is 45 ℃ and the reaction time is 12 hours.
The invention has the advantages that:
(1) the reaction conditions are mild, the elemental selenium is cheap and easy to obtain, the range of reaction substrates is wide, and the tolerance of functional groups is good;
(2) the reaction is efficient, the yield is high, the post-treatment is simple, the operation is simple and convenient, and the method is suitable for large-scale industrial production;
(3) elemental selenium is used as a selenium source, so that the atom utilization rate is high, and simultaneously, the stink of diselenide in the traditional reaction is avoided;
(4) no metal catalysis required by the traditional reaction;
(5) water can be used as a reaction solvent, and the green chemical concept is met.
Detailed Description
The present invention is described in detail below with reference to specific examples, but the use and purpose of the exemplary embodiments are merely to exemplify the present invention, and do not set forth any limitation on the actual scope of the present invention in any form, and the scope of the present invention is not limited thereto.
The data and purity of the novel compounds given in the following examples were determined by nuclear magnetic resonance.
Example 1
Synthesis of 2- (3-indolslenyl) -1-cyclohexyl alcohol:
adding a stirrer, selenium powder (0.8mmol), lithium tert-butoxide (1.2mmol), phase transfer catalyst tetrabutylammonium iodide (0.8mmol) and indole (0.4mmol) into a 25mL Schlenk tube at room temperature, then vacuumizing, charging nitrogen gas, vacuumizing and charging nitrogen gas back and forth three times, adding cyclohexene oxide (0.8mmol) and deionized water (2mL) under the protection of nitrogen gas, stirring at room temperature for 5min, finally moving to a heating tank at 45 ℃ for reaction, tracking and detecting by TLC (or GC-MS) in the reaction process, and completing the reaction after 12 h.
After the reaction is finished and the reaction mixture is cooled, the reaction mixture is firstly diluted by 15mL of water, then extracted by 45mL of ethyl acetate for three times, the organic phase of the three times is collected, then the organic phase is dried by anhydrous sodium sulfate, filtered, decompressed and concentrated, and finally the PE/EA-4: l is used for column purification to obtain the product. The product was a yellow oily liquid in 97% yield.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(500MHz,CDCl3):δ8.83(s,1H),7.33(d,J＝7.5Hz,1H),7.36(d,J＝7.5Hz,1H),7.28(s,1H),7.25-7.18(m,2H),3.34(s,1H),2.70-2.65(m,1H),2.16-2.05(m,1H),2.16-2.05(m,2H),1.64-1.50(m,2H),1.34-1.04(m,4H)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13C NMR(125MHz,CDCl3):δ136.3,131.9,131.2,122.7,120.7,120.2,111.5,94.8,72.3,52.7,33.8,33.4,26.8,24.5。
as can be seen, the product obtained is 2- (3-indolslenyl) -1-cyclohexyl alcohol.
Example 2
Synthesis of 2- (5-fluoro-3-indolslenyl) -1-cyclohexyl alcohol:
adding a stirrer, selenium powder (0.8mmol), lithium tert-butoxide (1.2mmol), tetrabutylammonium iodide (0.8mmol) and 5-fluoro-indole (0.4mmol) into a 25mL Schlenk tube at room temperature, vacuumizing, charging nitrogen gas, vacuumizing and charging nitrogen gas back and forth three times, adding cyclohexene oxide (0.8mmol) and deionized water (2mL) under the protection of nitrogen gas, stirring at room temperature for 5min, transferring to a heating tank at 45 ℃ for reaction, tracking and detecting by TLC (or GC-MS) in the reaction process, and finishing the reaction after 12 h.
After the reaction is finished and the reaction mixture is cooled, the reaction mixture is firstly diluted by 15mL of water, then extracted by 45mL of ethyl acetate for three times, the organic phase of the three times is collected, then the organic phase is dried by anhydrous sodium sulfate, filtered, decompressed and concentrated, and finally the PE/EA-4: l is used for column purification to obtain the product. The product was a yellow oily liquid in 70% yield.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(500MHz,CDCl3):δ8.69(s,1H),7.39-7.31(m,3H),7.01-6.97(m,1H),3.27-3.21(m,1H),3.15(s,1H),2.71-2.65(m,1H),2.17-2.07(m,2H),1.68-1.54(m,2H),1.35-1.18(m,4H)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13C NMR(125MHz,CDCl3):δ158.6(d,J＝233.8Hz),133.4,132.7,132.1(d,J＝10.0Hz),112.1(d,J＝10.0Hz),111.2(d,J＝26.3Hz),105.3(d,J＝23.8Hz),94.9,72.1,52.8,33.7,33.4,26.8,24.5。
the resulting product was found to be 2- (5-fluoro-3-indolslenyl) -1-cyclohexyl alcohol.
Example 3
Synthesis of 2- (6-chloro-3-indolslenyl) -1-cyclohexyl alcohol:
adding a stirrer, selenium powder (0.8mmol), lithium tert-butoxide (1.2mmol), tetrabutylammonium iodide (0.8mmol) and 6-chloro-indole (0.4mmol) into a 25mL Schlenk tube at room temperature, vacuumizing, charging nitrogen gas, vacuumizing and charging nitrogen gas back and forth three times, adding cyclohexene oxide (0.8mmol) and deionized water (2mL) under the protection of nitrogen gas, stirring at room temperature for 5min, transferring to a heating tank at 45 ℃ for reaction, tracking and detecting by TLC (or GC-MS) in the reaction process, and finishing the reaction after 12 h.
After the reaction is finished and the reaction mixture is cooled, the reaction mixture is firstly diluted by 15mL of water, then extracted by 45mL of ethyl acetate for three times, the organic phase of the three times is collected, then the organic phase is dried by anhydrous sodium sulfate, filtered, decompressed and concentrated, and finally the PE/EA-4: l is used for column purification to obtain the product. The product was a yellow oily liquid in 92% yield.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(500MHz,CDCl3):δ9.12(s,1H),7.61(d,J＝8.5Hz,1H),7.36(d,J＝1.5Hz,1H),7.28(d,J＝2.5Hz,1H),7.16-7.13(m,1H),3.35(s,1H),3.27-3.22(m,1H),2.70-2.64(m,1H),2.13-2.01(m,2H),1.68-1.51(m,2H),1.33-1.16(m,4H)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13C NMR(125MHz,CDCl3):δ136.6,132.6,129.9,128.6,121.4,121.2,111.4,94.9,72.3,52.6,33.8,33.4,26.8,24.5。
the resulting product was found to be 2- (6-chloro-3-indolslenyl) -1-cyclohexyl alcohol.
Example 4
Synthesis of 2- (6-methyl-3-indolslenyl) -1-cyclohexyl alcohol:
adding a stirrer, selenium powder (0.8mmol), lithium tert-butoxide (1.2mmol), tetrabutylammonium iodide (0.8mmol) and 6-methyl-indole (0.4mmol) into a 25mL Schlenk tube at room temperature, vacuumizing, charging nitrogen gas, vacuumizing and charging nitrogen gas back and forth three times, adding cyclohexene oxide (0.8mmol) and deionized water (2mL) under the protection of nitrogen gas, stirring at room temperature for 5min, transferring to a heating tank at 45 ℃ for reaction, tracking and detecting by TLC (or GC-MS) in the reaction process, and finishing the reaction after 12 h.
After the reaction is finished and the reaction mixture is cooled, the reaction mixture is firstly diluted by 15mL of water, then extracted by 45mL of ethyl acetate for three times, the organic phase of the three times is collected, then the organic phase is dried by anhydrous sodium sulfate, filtered, decompressed and concentrated, and finally the PE/EA-4: l is used for column purification to obtain the product. The product was a yellow oily liquid in 83% yield.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(500MHz,CDCl3):δ8.71(s,1H),7.60(d,J＝8.0Hz,1H),7.22(s,1H),7.17(s,1H),7.03(d,J＝8.0Hz,1H),3.33(s,1H),3.27-3.21(m,1H),2.68-2.63(m,1H),2.47(s,3H),2.18-2.08(m,2H),1.64-1.50(m,2H),1.34-1.17(m,4H)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13C NMR(125MHz,CDCl3):δ136.7,132.5,131.3,129.1,122.5,119.9,111.4,94.4,72.1,52.6,33.7,33.4,26.8,24.5,21.7。
as can be seen, the product obtained is 2- (6-methyl-3-indolslenyl) -1-cyclohexyl alcohol.
Example 5
Synthesis of 2- (6-methoxy-3-indolslenyl) -1-cyclohexyl alcohol:
adding a stirrer, selenium powder (0.8mmol), lithium tert-butoxide (1.2mmol), tetrabutylammonium iodide (0.8mmol) and 6-methoxy-indole (0.4mmol) into a 25mL Schlenk tube at room temperature, vacuumizing, charging nitrogen gas, vacuumizing and charging nitrogen gas back and forth three times, adding cyclohexene oxide (0.8mmol) and deionized water (2mL) under the protection of nitrogen gas, stirring at room temperature for 5min, transferring to a heating tank at 45 ℃ for reaction, tracking and detecting by TLC (or GC-MS) in the reaction process, and finishing the reaction after 12 h.
After the reaction is finished and the reaction mixture is cooled, the reaction mixture is firstly diluted by 15mL of water, then extracted by 45mL of ethyl acetate for three times, the organic phase of the three times is collected, then the organic phase is dried by anhydrous sodium sulfate, filtered, decompressed and concentrated, and finally the PE/EA-4: l is used for column purification to obtain the product. The product was a yellow oily liquid in 79% yield.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(500MHz,CDCl3):δ8.80(s,1H),7.28-7.25(m,2H),7.18(d,J＝2.5Hz,1H),6.90-6.87(m,1H),3.88(s,3H),3.30(s,1H),3.29-3.24(m,1H),2.70-2.65(m,1H),2.16-2.03(m,3H),1.66-1.51(m,2H),1.35-1.17(m,3H)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13C NMR(125MHz,CDCl3):δ154.9,132.4,131.9,131.2,112.9,112.2,101.7,94.3,72.1,55.9,52.6,33.7,33.3,26.8,24.4。
the resulting product was found to be 2- (6-methoxy-3-indolslenyl) -1-cyclohexyl alcohol.
Example 6
Synthesis of 1- (3-indolslenyl) -2-butanol:
adding a stirrer, selenium powder (0.8mmol), lithium tert-butoxide (1.2mmol), tetrabutylammonium iodide (0.8mmol) and indole (0.4mmol) into a 25mL Schlenk tube at room temperature, vacuumizing, charging nitrogen gas, vacuumizing and charging nitrogen gas repeatedly for three times, adding 1, 2-epoxybutane (0.8mmol) and deionized water (2mL) under the protection of nitrogen gas, stirring at room temperature for 5min, moving to a heating tank at 45 ℃ for reaction, tracking and detecting by TLC (or GC-MS) in the reaction process, and finishing the reaction after 12 h.
After the reaction is finished and the reaction mixture is cooled, the reaction mixture is firstly diluted by 15mL of water, then extracted by 45mL of ethyl acetate for three times, the organic phase of the three times is collected, then the organic phase is dried by anhydrous sodium sulfate, filtered, decompressed and concentrated, and finally the PE/EA-4: l is used for column purification to obtain the product. The product was a yellow oily liquid in 92% yield.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(500MHz,CDCl3):δ8.52(s,1H),7.72(d,J＝7.5Hz,1H),7.35(d,J＝7.5Hz,1H),7.28(d,J＝2.5Hz,1H),7.26-7.21(m,2H),3.54-3.45(m,1H),2.93-2.90(m,1H),2.72(s,1H),2.71-2.59(m,1H),1.53-1.47(m,2H),0.88(t,J＝7.0Hz,3H)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13C NMR(125MHz,CDCl3):δ136.3,130.4,129.9,122.7,120.6,129.9,111.5,97.5,71.3,37.0,29.1,70.1。
thus, the obtained product is 1- (3-indolslenyl) -2-butanol.
Example 7
Synthesis of 1- (3-indolslenyl) -2-methyl-2-propanol:
adding a stirrer, selenium powder (0.8mmol), lithium tert-butoxide (1.2mmol), tetrabutylammonium iodide (0.8mmol) and indole (0.4mmol) into a 25mL Schlenk tube at room temperature, vacuumizing, charging nitrogen gas, vacuumizing back and forth and charging nitrogen gas three times, adding methyl propylene oxide (0.8mmol) and deionized water (2mL) under the protection of nitrogen gas, stirring for 5min at room temperature, transferring to a heating tank at 45 ℃ for reaction, tracking and detecting by TLC (or GC-MS) in the reaction process, and finishing the reaction after 12 h.
After the reaction is finished and the reaction mixture is cooled, the reaction mixture is firstly diluted by 15mL of water, then extracted by 45mL of ethyl acetate for three times, the organic phase of the three times is collected, then the organic phase is dried by anhydrous sodium sulfate, filtered, decompressed and concentrated, and finally the PE/EA-4: l is used for column purification to obtain the product. The product was a yellow oily liquid with a yield of 80%.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(500MHz,CDCl3):δ8.55(s,1H),7.73(d,J＝7.5Hz,1H),7.34(d,J＝7.5Hz,1H),7.28(s,1H),7.23-7.18(m,2H),2.96(s,2H),2.46(s,1H),1.30(s,6H)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13C NMR(125MHz,CDCl3):δ136.3,129.9,129.7,122.7,120.6,119.9,111.5,99.4,70.9,44.9,28.9。
thus, the obtained product is 1- (3-indolslenyl) -2-methyl-2-propanol.
Example 8
Synthesis of 1- (3-indolslenyl) -3, 3-dimethyl-2-butanol:
adding a stirrer, selenium powder (0.8mmol), lithium tert-butoxide (1.2mmol), tetrabutylammonium iodide (0.8mmol) and indole (0.4mmol) into a 25mL Schlenk tube at room temperature, vacuumizing, charging nitrogen gas, vacuumizing and charging nitrogen gas repeatedly for three times, adding 3, 3-dimethyl butylene oxide (0.8mmol) and deionized water (2mL) under the protection of nitrogen gas, stirring at room temperature for 5min, moving to a heating tank at 45 ℃ for reaction, tracking and detecting by TLC (or GC-MS) in the reaction process, and finishing the reaction after 12 h.
After the reaction is finished and the reaction mixture is cooled, the reaction mixture is firstly diluted by 15mL of water, then extracted by 45mL of ethyl acetate for three times, the organic phase of the three times is collected, then the organic phase is dried by anhydrous sodium sulfate, filtered, decompressed and concentrated, and finally the PE/EA-4: l is used for column purification to obtain the product. The product was a yellow oily liquid in 83% yield.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(500MHz,CDCl3):δ8.58(s,1H),7.73(d,J＝8.0Hz,1H),7.37(d,J＝8.0Hz,1H),7.37(d,J＝8.0Hz,1H),7.31(s,1H),7.26-7.19(m,2H),3.25(d,J＝11.5Hz,1H),3.04(d,J＝12.5Hz,1H),2.80(s,1H),2.59(t,J＝11.5Hz,1H),0.84(s,9H)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13C NMR(125MHz,CDCl3):δ136.4,130.5,130.0,122.8,120.6,119.9,111.5,97.3,77.5,34.8,33.5,25.9。
thus, the obtained product is 1- (3-indolslenyl) -3, 3-dimethyl-2-butanol.
Example 9
Synthesis of 2- (3-indolslenyl) -1-cyclopentanol:
adding a stirrer, selenium powder (0.8mmol), lithium tert-butoxide (1.2mmol), tetrabutylammonium iodide (0.8mmol) and indole (0.4mmol) into a 25mL Schlenk tube at room temperature, vacuumizing, charging nitrogen, vacuumizing and charging nitrogen repeatedly for three times, adding cyclopentene oxide (0.8mmol) and deionized water (2mL) under the protection of nitrogen, stirring at room temperature for 5min, transferring to a 45 ℃ heating tank for reaction, detecting by TLC (or GC-MS) tracking during the reaction, and finishing the reaction after 12 h.
After the reaction is finished and the reaction mixture is cooled, the reaction mixture is firstly diluted by 15mL of water, then extracted by 45mL of ethyl acetate for three times, the organic phase of the three times is collected, then the organic phase is dried by anhydrous sodium sulfate, filtered, decompressed and concentrated, and finally the PE/EA-4: l is used for column purification to obtain the product. The product was a yellow oily liquid in 89% yield.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(500MHz,CDCl3):δ8.59(s,1H),7.74(d,J＝7.5Hz,1H),7.33(d,J＝7.5Hz,1H),7.26-7.17(m,3H),4.04-4.01(m,1H),3.13-3.09(m,1H),2.13-2.05(m,2H),2.01-1.95(m,1H),1.69-1.46(m,4H)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13C NMR(125MHz,CDCl3):δ136.2,131.2,130.7,122.7,120.6,120.1,111.4,97.2,78.9,49.6,32.3,30.7,21.8。
as can be seen, the product obtained is 2- (3-indolslenyl) -1-cyclopentanol.
Example 10
Synthesis of 1- (3-indolseleno) -3- (furyl-2-methoxy) -2-propanol:
adding a stirrer, selenium powder (0.8mmol), lithium tert-butoxide (1.2mmol), tetrabutylammonium iodide (0.8mmol) and indole (0.4mmol) into a 25mL Schlenk tube at room temperature, vacuumizing, charging nitrogen gas, vacuumizing and charging nitrogen gas repeatedly for three times, adding 2-furylmethyl glycidyl ether (0.8mmol) and deionized water (2mL) under the protection of nitrogen gas, stirring at room temperature for 5min, moving to a heating tank at 45 ℃ for reaction, tracking and detecting by TLC (or GC-MS) in the reaction process, and finishing the reaction after 12 h.
After the reaction is finished and the reaction mixture is cooled, the reaction mixture is firstly diluted by 15mL of water, then extracted by 45mL of ethyl acetate for three times, the organic phase of the three times is collected, then the organic phase is dried by anhydrous sodium sulfate, filtered, decompressed and concentrated, and finally the PE/EA-4: l is used for column purification to obtain the product. The product was a yellow oily liquid in 82% yield.
The data of the nuclear magnetic resonance hydrogen spectrum of the obtained product are as follows:
1H NMR(500MHz,CDCl3):δ8.65(s,1H),7.69(d,J＝7.5Hz,1H),7.36-7.30(m,2H),7.23-7.16(m,3H),6.30-6.27(m,1H),6.25-6.22(m,1H),4.40(s,2H),3.80-3.72(m,1H),3.54-3.50(m,1H),3.46-3.42(m,1H),2.91(s,1H),2.82-2.78(m,1H),2.70-2.66(m,1H)。
the data of the nuclear magnetic resonance carbon spectrum of the obtained product are as follows:
13C NMR(125MHz,CDCl3):δ151.3,142.9,136.3,130.7,130.0,122.7,120.6,119.9,111.6,110.3,109.6,97.3,72.8,69.5,65.1,32.5。
the resulting product was found to be 1- (3-indolseleno) -3- (furyl-2-methoxy) -2-propanol.
In examples 1 to 10, the reaction solvent is selected from water (in which tetrabutylammonium iodide is added as a phase transfer catalyst), and the water is more in accordance with the green chemistry concept. Through tests, the reaction solvent can also select organic solvents such as alcohol, ether, chloralkane, aromatic hydrocarbon, ester, heterocyclic aromatic hydrocarbon, aliphatic hydrocarbon and the like besides water, wherein:
(1) the alcohol can be either a monohydric alcohol or a polymer of monohydric alcohols, preferably a C1-C4 linear or branched alkyl alcohol, including but not limited to methanol, ethanol, n-propanol, isopropanol, n-butanol, and polyethylene glycol.
(2) The ethers may be simple ethers, mixed ethers, cyclic ethers, preferably cyclic ethers. Ethers include, but are not limited to, diethyl ether, 1, 4-dioxane, and Tetrahydrofuran (THF).
(3) Chlorinated alkanes include, but are not limited to, dichloromethane, chloroform, carbon tetrachloride, and 1, 2-dichloroethane.
(4) Aromatic hydrocarbons include, but are not limited to, benzene, chlorobenzene, o-dichlorobenzene, and xylenes.
(5) Organic solvents such as tetrabutylammonium iodide (TBAI), ethyl acetate, pyridine, and n-hexane may also be used as the reaction solvent in the present invention.
Examples 11 to 19
The same operations as in example 1 were carried out except that the reaction solvents were different in examples 11 to 19, and the yields of the organic solvents and the corresponding products used in the respective examples are shown in the following table:
| numbering | Reaction solvent | Reaction yield (%) |
| Example 11 | Dimethyl sulfoxide | Is not reacted |
| Example 12 | N, N-dimethylformamide | Is not reacted |
| Example 13 | Toluene | Is not reacted |
| Example 14 | NMP | Is not reacted |
| Example 15 | N-propanol | 98％ |
| Example 16 | 1, 4-dioxahexaalkane | 20％ |
| Example 17 | Tetrahydrofuran (THF) | 35％ |
| Example 18 | Isopropanol (I-propanol) | 70％ |
| Example 19 | Acetonitrile | Trace amount of |
From the above table, it can be seen that:
(1) when organic solvents of moderate polarity (tetrahydrofuran, 1, 4-dioxahexaalkane) are used, the reaction yield is low, only 20% and 35% (examples 16 and 17);
(2) when a less polar aprotic solvent was used (acetonitrile), the reaction hardly occurred (example 19);
(3) when a high boiling polar solvent (dimethylsulfoxide, N-dimethylformamide, N-methylpyrrolidone) is used, the reaction does not occur (example 11, example 12, example 14);
(4) when an aprotic apolar solvent was used (toluene), the reaction did not occur either (example 13);
(5) the reaction is better when polar protic solvents are used (n-propanol, isopropanol), with a yield of 98% using n-propanol (example 15) and 70% isopropanol (example 18).
The method comprehensively considers the factors of environmental protection and the like, and the best choice is to add a phase transfer catalyst tetrabutylammonium iodide (TBAI) into water as a reaction solvent.
In examples 1 to 10, the inorganic base is lithium tert-butoxide. Tests show that potassium tert-butoxide, sodium phosphate, potassium phosphate, cesium carbonate, potassium hydroxide, sodium ethoxide and sodium methoxide can be used in the invention instead of lithium tert-butoxide.
Examples 20 to 28
Examples 20 to 28 were identical to example 1 except that the inorganic base was different, and the yields of the inorganic base and the corresponding product used in each example are shown in the following table:
from the above table, it can be seen that:
(1) when strong alkali is used, the reaction is easy to carry out, wherein when potassium tert-butoxide and tert-butyl alcohol sodium salt are used, the yield is 83 percent and 75 percent respectively, and the method is worth mentioning;
(2) the reaction differed greatly when a medium strength base was used, with 83% yield using cesium carbonate and moderate (66%) yield using potassium phosphate, and very poorly (product traces) using potassium carbonate;
(3) when a weak inorganic base is used, no reaction occurs (example 25, example 26);
(4) when an organic base was used, the reaction was also poor (example 27) or even non-reactive (example 28).
In addition, in examples 1 to 19, the inorganic base we used was a lithium tert-butoxide salt, and the reaction occurred almost quantitatively, so lithium tert-butoxide was the most preferable inorganic base.
In examples 1 to 28, the molar ratio of the amount of the inorganic base to the amount of the indole was 3: 1. Through experiments, the molar ratio of the use amount of the inorganic base to the use amount of the indole can be properly reduced to 1: 1.
It is clear from all the above embodiments that the method of the present invention can synthesize the 3-indoselenol compound with high yield and high purity, and has the advantages of mild reaction conditions, wide range of reaction substrates, good tolerance of functional groups, simple post-treatment, simple and convenient operation, suitability for large-scale industrial production, and provision of a brand new synthesis route for the efficient and rapid synthesis of the compounds.
Claims (5)
- The synthesis method of the 3-indoneselenol organic compound is characterized in that any one of indole, 5-fluoro-indole, 6-chloro-indole, 6-methyl-indole and 6-methoxy-indole, any one of cyclohexene oxide, cyclopentene oxide, 1, 2-epoxybutane, methyl propylene oxide, 3-dimethyl butylene oxide and 2-furanmethyl glycidyl ether is used as a reaction substrate, elemental selenium is used as a selenium source, water or an organic solvent is used as a reaction solvent, under the action of inorganic base in a nitrogen atmosphere, a 3-indoneselenol compound is obtained without transition metal catalysis, and when water is used as the reaction solvent, a phase transfer catalyst tetrabutylammonium iodide is added into the water;wherein the organic solvent is at least one of tetrahydrofuran, 1, 4-dioxane, n-propanol and isopropanol;the inorganic base is at least one of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium phosphate, potassium phosphate, cesium carbonate, potassium hydroxide and sodium hydroxide;the molar ratio of the use amount of the inorganic base to the use amount of the indole is 1-3:1, and the molar ratio of the use amount of the inorganic base to the use amount of the 5-fluoro-indole, the 6-chloro-indole, the 6-methyl-indole or the 6-methoxy-indole is 3: 1.
- 2. The method for synthesizing the 3-indoselenol organic compound as claimed in claim 1, wherein the elemental selenium is selenium powder, and the molar ratio of the selenium powder to the indole is 1-3: 1.
- 3. The method for synthesizing 3-indoselenol organic compounds according to claim 1, wherein the ratio of water to tetrabutylammonium iodide is 2mL:0.8 mmol.
- 4. The method for synthesizing 3-indoselenol organic compounds according to claim 1, wherein the reaction temperature is 20-60 ℃ and the reaction time is 6-16 h.
- 5. The method for synthesizing 3-indoselenol organic compounds according to claim 4, wherein the reaction temperature is 45 ℃ and the reaction time is 12 hours.
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