CN108047118A - The synthetic method of 3- indoles seleno alcohols organic compounds - Google Patents
The synthetic method of 3- indoles seleno alcohols organic compounds Download PDFInfo
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- CN108047118A CN108047118A CN201810023791.8A CN201810023791A CN108047118A CN 108047118 A CN108047118 A CN 108047118A CN 201810023791 A CN201810023791 A CN 201810023791A CN 108047118 A CN108047118 A CN 108047118A
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- C07—ORGANIC CHEMISTRY
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
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Abstract
The invention discloses the synthetic methods of 3 indoles seleno alcohols organic compounds, it is characterized in that, with Benzazole compounds and cyclohexene oxide/cyclopentene oxide/1,2 epoxy butanes/methyloxetane/3, the furfuryl glycidol ether of 3 isobutylene butane/2 is reaction substrate, using elemental selenium as selenium source, reaction dissolvent is made with water or organic solvent, when making reaction dissolvent with water, Xiang Shuizhong adds phase transfer catalyst tetrabutylammonium iodide, it is no transition metal-catalyzed to obtain 3 indoles seleno alcohol compounds under the action of inorganic base in nitrogen atmosphere.The invention has the beneficial effects that：Method using the present invention can synthesize to obtain 3 indoles seleno alcohol compounds with high yield and high-purity, and reaction condition is mild, reaction substrate scope is wide, functional group's tolerance is good, post processing is simple, it is easy to operate, it is suitble to large-scale industrial production, brand-new synthetic route is provided for the efficient quick synthesis of such compound.
Description
Technical field
The present invention relates to the synthetic methods of organic compound, and in particular to the synthesis of 3- indoles seleno alcohols organic compounds
Method belongs to organic compound synthesis technical field.
Background technology
3- indoles seleno alcohols organic compounds are one kind of unsymmetrical selenides compound in selenium-containing compound, are had good
Physiological activity, selenium-containing compound is developed by new chemical constitution and synthesizes 3- indoles selenium for a kind of new green synthesis method
Base alcohol compound has great significance in organic synthesis and pharmaceutical chemistry.
2003, Venkataraman et al. reported CuI/2,9- dimethyl -1,10- ferrosins catalyst system and catalyzing catalysis virtue
The method that base iodine and selenophenol prepare asymmetric diaryl list selenide.This method is adopted according to the difference of electronic effect on aryl iodide
With different alkali：When substituent group is electron rich group on iodobenzene, highly basic t-BuONa is used；When substituent group is electric to inhale on iodobenzene
During sub- substituent group, then using weak base K2CO3.Although a series of asymmetric selenide can be prepared, selenophenol has dislikes this method
It is smelly and have severe toxicity, it should not use.
2013, Zeni seminars developed under ferric trichloride catalytic, in dichloromethane solution, O- alkane alkynyl aniline
And its method that derivative and diaryl (alkyl) diselenide prepare corresponding 3- Organic Seleniums benzazolyl compounds and its derivative.The party
The diselenide of method is completely on product, and atomic efficiency is high, and mild condition, and good economy performance, energy consumption is low, and synthesize
3- Organic Seleniums benzazolyl compounds can have potential use value by selenium lithium exchange system for increasingly complex indole derivatives.
But this method needs transition metal-catalyzed, while needs diselenide as raw material, unpleasant foul smell and is urged using metal
Agent does not meet environment protection requirement.
The content of the invention
For solve the deficiencies in the prior art, it is an object of the invention to provide a kind of mild condition, it is easy to operate, using list
Matter selenium as selenium source, be not added with any metal make catalyst synthesis 3- indoles seleno alcohols organic compounds method.
In order to realize above-mentioned target, the present invention adopts the following technical scheme that：
The synthetic method of 3- indoles seleno alcohols organic compounds, which is characterized in that with Benzazole compounds and oxidation ring
Hexene/cyclopentene oxide/1,2- epoxy butanes/methyloxetane/3,3- isobutylenes butane/2- furfuryls shrink sweet
Oily ether is reaction substrate, using elemental selenium as selenium source, makees reaction dissolvent with water or organic solvent, when making reaction dissolvent with water, Xiang Shui
Middle addition phase transfer catalyst tetrabutylammonium iodide, it is no transition metal-catalyzed under the action of inorganic base in nitrogen atmosphere
To 3- indoles seleno alcohol compounds.
The synthetic method of foregoing 3- indoles seleno alcohols organic compounds, which is characterized in that foregoing elemental selenium is selenium powder,
The dosage of foregoing selenium powder and the dosage molar ratio of indoles are 1-3:1.
The synthetic method of foregoing 3- indoles seleno alcohols organic compounds, which is characterized in that aforementioned organic solvents four
At least one of hydrogen furans, 1,4- dioxane, normal propyl alcohol and isopropanol.
The synthetic method of foregoing 3- indoles seleno alcohols organic compounds, which is characterized in that foregoing water and tetrabutyl iodine
The ratio for changing ammonium is 2mL:0.8mmol.
The synthetic method of foregoing 3- indoles seleno alcohols organic compounds, which is characterized in that aforementioned inorganic alkali is tertiary fourth
In potassium alcoholate, sodium tert-butoxide, tert-butyl alcohol lithium, sodium phosphate, potassium phosphate, cesium carbonate, potassium hydroxide, sodium hydroxide and pyrrolidines at least
It is a kind of.
The synthetic method of foregoing 3- indoles seleno alcohols organic compounds, which is characterized in that the dosage of aforementioned inorganic alkali
Dosage molar ratio with indoles is 1-3:1.
The synthetic method of foregoing 3- indoles seleno alcohols organic compounds, which is characterized in that reaction temperature 20-60
DEG C, reaction time 6-16h.
The synthetic method of foregoing 3- indoles seleno alcohols organic compounds, which is characterized in that reaction temperature is 45 DEG C, instead
It is 12h between seasonable.
The invention has the beneficial effects that：
(1) reaction condition is mild, and elemental selenium is cheap and easy to get, and reaction substrate scope is wide, and functional group's tolerance is good；
(2) reaction is efficient, high income, and post processing is simple, easy to operate, is suitble to large-scale industrial production；
(3) using elemental selenium as selenium source, atom utilization is high, while avoids the stench of diselenide in tradition reaction；
(4) metal catalytic necessary to being reacted without tradition；
(5) reaction dissolvent can be made with water, meets green chemical concept.
Specific embodiment
Below by specific embodiment, the present invention is described in detail, but the purposes and mesh of this exemplary embodiments
Be only used for enumerate the present invention, any type of any restriction not is formed to the real protection scope of the present invention, it is more non-to incite somebody to action this
The protection domain of invention is confined to this.
The data and purity of noval chemical compound given by following embodiment are identified by nuclear magnetic resonance.
Embodiment 1
The synthesis of 2- (3- indoles seleno) -1- cyclohexyl alcohols：
At room temperature, in 25mL Schlenk pipes add in stirrer, selenium powder (0.8mmol), tert-butyl alcohol lithium (1.2mmol),
Phase transfer catalyst tetrabutylammonium iodide (0.8mmol), indoles (0.4mmol), then vacuumize, inflated with nitrogen, vacuumize back and forth-
Inflated with nitrogen three times, cyclohexene oxide (0.8mmol), deionized water (2mL) is added under the protection of nitrogen, is stirred at room temperature afterwards
5min is mixed, finally moves in 45 DEG C of heating tank and reacts, TLC (or GC-MS) tracing detection is used in reaction process, after testing,
Reaction finishes after 12h.
Reaction is finished after reaction mixture cooling, and reaction mixture is first diluted with 15mL water, then with 45mL acetic acid second
Ester extracts three times, collects organic phase three times, dries organic phase with anhydrous sodium sulfate afterwards, and filtering is concentrated under reduced pressure, finally uses
PE/EA=4:L crosses column purification, obtains product.Product is yellow oily liquid, yield 97%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3):δ 8.83 (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 carbon-13 nmr spectra of products therefrom 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 it can be seen that products therefrom is 2- (3- indoles seleno) -1- cyclohexyl alcohols.
Embodiment 2
The synthesis of 2- (the fluoro- 3- indoles selenos of 5-) -1- cyclohexyl alcohols：
At room temperature, in 25mL Schlenk pipes add in stirrer, selenium powder (0.8mmol), tert-butyl alcohol lithium (1.2mmol),
Tetrabutylammonium iodide (0.8mmol), the fluoro- indoles of 5- (0.4mmol), then vacuumize, inflated with nitrogen, vacuumize-inflated with nitrogen back and forth
Three times, cyclohexene oxide (0.8mmol), deionized water (2mL) are added under the protection of nitrogen, is stirred at room temperature afterwards
5min is finally moved in 45 DEG C of heating tank and reacted, and TLC (or GC-MS) tracing detection, after testing, 12h are used in reaction process
Reaction finishes afterwards.
Reaction is finished after reaction mixture cooling, and reaction mixture is first diluted with 15mL water, then with 45mL acetic acid second
Ester extracts three times, collects organic phase three times, dries organic phase with anhydrous sodium sulfate afterwards, and filtering is concentrated under reduced pressure, finally uses
PE/EA=4:L crosses column purification, obtains product.Product is yellow oily liquid, yield 70%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom 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 carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,CDCl3):δ 158.6 (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。
As it can be seen that products therefrom is 2- (the fluoro- 3- indoles selenos of 5-) -1- cyclohexyl alcohols.
Embodiment 3
The synthesis of 2- (the chloro- 3- indoles selenos of 6-) -1- cyclohexyl alcohols：
At room temperature, in 25mL Schlenk pipes add in stirrer, selenium powder (0.8mmol), tert-butyl alcohol lithium (1.2mmol),
Tetrabutylammonium iodide (0.8mmol), the chloro- indoles of 6- (0.4mmol), then vacuumize, inflated with nitrogen, vacuumize-inflated with nitrogen back and forth
Three times, cyclohexene oxide (0.8mmol), deionized water (2mL) are added under the protection of nitrogen, is stirred at room temperature afterwards
5min is finally moved in 45 DEG C of heating tank and reacted, and TLC (or GC-MS) tracing detection, after testing, 12h are used in reaction process
Reaction finishes afterwards.
Reaction is finished after reaction mixture cooling, and reaction mixture is first diluted with 15mL water, then with 45mL acetic acid second
Ester extracts three times, collects organic phase three times, dries organic phase with anhydrous sodium sulfate afterwards, and filtering is concentrated under reduced pressure, finally uses
PE/EA=4:L crosses column purification, obtains product.Product is yellow oily liquid, yield 92%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3):δ 9.12 (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 carbon-13 nmr spectra of products therefrom 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。
As it can be seen that products therefrom is 2- (the chloro- 3- indoles selenos of 6-) -1- cyclohexyl alcohols.
Embodiment 4
The synthesis of 2- (6- methyl -3- indoles seleno) -1- cyclohexyl alcohols：
At room temperature, in 25mL Schlenk pipes add in stirrer, selenium powder (0.8mmol), tert-butyl alcohol lithium (1.2mmol),
Tetrabutylammonium iodide (0.8mmol), 6- Methvl-indoles (0.4mmol), then vacuumize, inflated with nitrogen, vacuumize-nitrogen charging back and forth
Gas three times, cyclohexene oxide (0.8mmol), deionized water (2mL) is added under the protection of nitrogen, is stirred at room temperature afterwards
5min is finally moved in 45 DEG C of heating tank and reacted, and TLC (or GC-MS) tracing detection, after testing, 12h are used in reaction process
Reaction finishes afterwards.
Reaction is finished after reaction mixture cooling, and reaction mixture is first diluted with 15mL water, then with 45mL acetic acid second
Ester extracts three times, collects organic phase three times, dries organic phase with anhydrous sodium sulfate afterwards, and filtering is concentrated under reduced pressure, finally uses
PE/EA=4:L crosses column purification, obtains product.Product is yellow oily liquid, yield 83%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3):δ 8.71 (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 carbon-13 nmr spectra of products therefrom 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 it can be seen that products therefrom is 2- (6- methyl -3- indoles seleno) -1- cyclohexyl alcohols.
Embodiment 5
The synthesis of 2- (6- methoxyl group -3- indoles seleno) -1- cyclohexyl alcohols：
At room temperature, in 25mL Schlenk pipes add in stirrer, selenium powder (0.8mmol), tert-butyl alcohol lithium (1.2mmol),
Tetrabutylammonium iodide (0.8mmol), 6- Methoxv-indoles (0.4mmol), then vacuumize, inflated with nitrogen, vacuumize-fill back and forth
Nitrogen three times, cyclohexene oxide (0.8mmol), deionized water (2mL) is added under the protection of nitrogen, is stirred at room temperature afterwards
5min is finally moved in 45 DEG C of heating tank and reacted, and TLC (or GC-MS) tracing detection, after testing, 12h are used in reaction process
Reaction finishes afterwards.
Reaction is finished after reaction mixture cooling, and reaction mixture is first diluted with 15mL water, then with 45mL acetic acid second
Ester extracts three times, collects organic phase three times, dries organic phase with anhydrous sodium sulfate afterwards, and filtering is concentrated under reduced pressure, finally uses
PE/EA=4:L crosses column purification, obtains product.Product is yellow oily liquid, yield 79%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3):δ 8.80 (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 carbon-13 nmr spectra of products therefrom 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。
As it can be seen that products therefrom is 2- (6- methoxyl group -3- indoles seleno) -1- cyclohexyl alcohols.
Embodiment 6
The synthesis of 1- (3- indoles seleno) -2- butanol：
At room temperature, in 25mL Schlenk pipes add in stirrer, selenium powder (0.8mmol), tert-butyl alcohol lithium (1.2mmol),
Tetrabutylammonium iodide (0.8mmol), indoles (0.4mmol), then vacuumize, inflated with nitrogen, vacuumize back and forth-inflated with nitrogen three times,
1,2- epoxy butanes (0.8mmol), deionized water (2mL) are added under the protection of nitrogen, 5min is stirred at room temperature afterwards, most
It moves in 45 DEG C of heating tank and reacts afterwards, using TLC (or GC-MS) tracing detection in reaction process, after testing, reacted after 12h
It finishes.
Reaction is finished after reaction mixture cooling, and reaction mixture is first diluted with 15mL water, then with 45mL acetic acid second
Ester extracts three times, collects organic phase three times, dries organic phase with anhydrous sodium sulfate afterwards, and filtering is concentrated under reduced pressure, finally uses
PE/EA=4:L crosses column purification, obtains product.Product is yellow oily liquid, yield 92%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3):δ 8.52 (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 carbon-13 nmr spectra of products therefrom 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。
As it can be seen that products therefrom is 1- (3- indoles seleno) -2- butanol.
Embodiment 7
The synthesis of 1- (3- indoles seleno) -2- methyl-2-propanols：
At room temperature, in 25mL Schlenk pipes add in stirrer, selenium powder (0.8mmol), tert-butyl alcohol lithium (1.2mmol),
Tetrabutylammonium iodide (0.8mmol), indoles (0.4mmol), then vacuumize, inflated with nitrogen, vacuumize back and forth-inflated with nitrogen three times,
Methyloxetane (0.8mmol), deionized water (2mL) are added under the protection of nitrogen, 5min is stirred at room temperature afterwards, most
It moves in 45 DEG C of heating tank and reacts afterwards, using TLC (or GC-MS) tracing detection in reaction process, after testing, reacted after 12h
It finishes.
Reaction is finished after reaction mixture cooling, and reaction mixture is first diluted with 15mL water, then with 45mL acetic acid second
Ester extracts three times, collects organic phase three times, dries organic phase with anhydrous sodium sulfate afterwards, and filtering is concentrated under reduced pressure, finally uses
PE/EA=4:L crosses column purification, obtains product.Product is yellow oily liquid, yield 80%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3):δ 8.55 (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 carbon-13 nmr spectra of products therefrom 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。
As it can be seen that products therefrom is 1- (3- indoles seleno) -2- methyl-2-propanols.
Embodiment 8
The synthesis of 1- (3- indoles seleno) -3,3- dimethyl -2- butanol：
At room temperature, in 25mL Schlenk pipes add in stirrer, selenium powder (0.8mmol), tert-butyl alcohol lithium (1.2mmol),
Tetrabutylammonium iodide (0.8mmol), indoles (0.4mmol), then vacuumize, inflated with nitrogen, vacuumize back and forth-inflated with nitrogen three times,
3,3- isobutylenes butane (0.8mmol), deionized water (2mL) are added under the protection of nitrogen, is stirred at room temperature afterwards
5min is finally moved in 45 DEG C of heating tank and reacted, and TLC (or GC-MS) tracing detection, after testing, 12h are used in reaction process
Reaction finishes.
Reaction is finished after reaction mixture cooling, and reaction mixture is first diluted with 15mL water, then with 45mL acetic acid second
Ester extracts three times, collects organic phase three times, dries organic phase with anhydrous sodium sulfate afterwards, and filtering is concentrated under reduced pressure, finally uses
PE/EA=4:L crosses column purification, obtains product.Product is yellow oily liquid, yield 83%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3):δ 8.58 (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 carbon-13 nmr spectra of products therefrom 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。
As it can be seen that products therefrom is 1- (3- indoles seleno) -3,3- dimethyl -2- butanol.
Embodiment 9
The synthesis of 2- (3- indoles seleno) -1- cyclopentanol：
At room temperature, in 25mL Schlenk pipes add in stirrer, selenium powder (0.8mmol), tert-butyl alcohol lithium (1.2mmol),
Tetrabutylammonium iodide (0.8mmol), indoles (0.4mmol), then vacuumize, inflated with nitrogen, vacuumize back and forth-inflated with nitrogen three times,
Cyclopentene oxide (0.8mmol), deionized water (2mL) are added under the protection of nitrogen, 5min is stirred at room temperature afterwards, finally
It moves in 45 DEG C of heating tank and reacts, using TLC (or GC-MS) tracing detection in reaction process, after testing, reacted after 12h
Finish.
Reaction is finished after reaction mixture cooling, and reaction mixture is first diluted with 15mL water, then with 45mL acetic acid second
Ester extracts three times, collects organic phase three times, dries organic phase with anhydrous sodium sulfate afterwards, and filtering is concentrated under reduced pressure, finally uses
PE/EA=4:L crosses column purification, obtains product.Product is yellow oily liquid, yield 89%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3):δ 8.59 (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 carbon-13 nmr spectra of products therefrom 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 it can be seen that products therefrom is 2- (3- indoles seleno) -1- cyclopentanol.
Embodiment 10
The synthesis of 1- (3- indoles seleno) -3- (furyl -2- methoxyl groups) -2- propyl alcohol：
At room temperature, in 25mL Schlenk pipes add in stirrer, selenium powder (0.8mmol), tert-butyl alcohol lithium (1.2mmol),
Tetrabutylammonium iodide (0.8mmol), indoles (0.4mmol), then vacuumize, inflated with nitrogen, vacuumize back and forth-inflated with nitrogen three times,
2- furfuryls glycidol ether (0.8mmol), deionized water (2mL) are added under the protection of nitrogen, is stirred at room temperature afterwards
5min is mixed, finally moves in 45 DEG C of heating tank and reacts, TLC (or GC-MS) tracing detection is used in reaction process, after testing,
12h reactions finish.
Reaction is finished after reaction mixture cooling, and reaction mixture is first diluted with 15mL water, then with 45mL acetic acid second
Ester extracts three times, collects organic phase three times, dries organic phase with anhydrous sodium sulfate afterwards, and filtering is concentrated under reduced pressure, finally uses
PE/EA=4:L crosses column purification, obtains product.Product is yellow oily liquid, yield 82%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3):δ 8.65 (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 carbon-13 nmr spectra of products therefrom 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。
As it can be seen that products therefrom is 1- (3- indoles seleno) -3- (furyl -2- methoxyl groups) -2- propyl alcohol.
In embodiment 1 into embodiment 10, we select reaction dissolvent is water (wherein added with phase transfer catalyst four
Butyl ammonium iodide), water more meets green chemical concept.Through experiment, reaction dissolvent in addition to water, can also select alcohol, ether, chlorine
For organic solvents such as alkane, aromatic hydrocarbon, ester, heterocyclic arene, aliphatic hydrocarbons, wherein：
(1) alcohol is either the alkane of the polymer of monohydric alcohol or monohydric alcohol, the preferably linear chain or branch chain of C1-C4
Base alcohol includes but not limited to methanol, ethyl alcohol, normal propyl alcohol, isopropanol, n-butanol and polyethylene glycol.
(2) ether is either simple ether or compound ether, can also be cyclic ethers, preferably cyclic ethers.Ether includes but unlimited
In ether, 1,4- dioxane and tetrahydrofuran (THF).
(3) chloralkane includes but not limited to dichloromethane, chloroform, carbon tetrachloride and 1,2- dichloroethanes.
(4) aromatic hydrocarbon includes but not limited to benzene, chlorobenzene, o-dichlorohenzene and dimethylbenzene.
(5) organic solvents such as tetrabutylammonium iodide (TBAI), ethyl acetate, pyridine, n-hexane can also be used as the present invention
Reaction dissolvent.
Embodiment 11 is to embodiment 19
In addition to reaction dissolvent difference, embodiment 11 to embodiment 19 is identical with other operations of embodiment 1, respectively
The yield of organic solvent used in embodiment and corresponding product is as shown in the table：
| Number | Reaction dissolvent | Reaction yield (%) |
| Embodiment 11 | Dimethyl sulfoxide (DMSO) | It does not react |
| Embodiment 12 | N,N-dimethylformamide | It does not react |
| Embodiment 13 | Toluene | It does not react |
| Embodiment 14 | NMP | It does not react |
| Embodiment 15 | Normal propyl alcohol | 98% |
| Embodiment 16 | Six alkane of 1,4- dioxies | 20% |
| Embodiment 17 | Tetrahydrofuran | 35% |
| Embodiment 18 | Isopropanol | 70% |
| Embodiment 19 | Acetonitrile | Trace |
As seen from the above table：
(1) when using the organic solvent of middle polarity (tetrahydrofuran, six alkane of Isosorbide-5-Nitrae-dioxy), reaction yield is relatively low, only
Only there was only 20%, 35% (embodiment 16, embodiment 17)；
(2) when using the aprotic solvent of low pole (acetonitrile), hardly (embodiment 19) occurs for reaction；
(3) (dimethyl sulfoxide (DMSO), N,N-dimethylformamide, N- crassitudes when using high boiling polar solvent
Ketone), reaction does not occur (embodiment 11, embodiment 12, embodiment 14)；
(4) when using aproticapolar solvent (toluene), (embodiment 13) does not also occur for reaction；
(5) when using polar aprotic solvent (normal propyl alcohol, isopropanol), reaction is preferable, wherein, it is reached using normal propyl alcohol yield
To 98% (embodiment 15), isopropanol takes second place, and is 70% (embodiment 18).
Consider the factors such as environmentally protective, phase transfer catalyst tetrabutylammonium iodide (TBAI) is added in using in water as instead
It is optimal selection to answer solvent.
In embodiment 1 into embodiment 10, inorganic base we select be tert-butyl alcohol lithium.Through experiment, potassium tert-butoxide, tertiary fourth
The all alternative tert-butyl alcohol lithium of sodium alkoxide, sodium phosphate, potassium phosphate, cesium carbonate, potassium hydroxide, sodium hydroxide, sodium ethoxide and sodium methoxide should
It is used for this invention.
Embodiment 20 is to embodiment 28
In addition to inorganic base difference, embodiment 20 to embodiment 28 is identical with other operations of embodiment 1, each reality
The yield for applying inorganic base used in example and corresponding product is as shown in the table：
As seen from the above table：
(1) when using highly basic, react and easily carry out, wherein, during using potassium tert-butoxide, tert-butyl alcohol sodium salt, yield difference
For 83%, 75%, it is worth mentioning at this point that；
(2) when using the alkali of moderate strength, reaction difference is very big, wherein, the use of yield during cesium carbonate is 83%, uses
Yield is moderate (66%) during potassium phosphate, and very poor (product trace) is then reacted using potassium carbonate；
(3) when using inorganic weak bases, reaction does not occur (embodiment 25, embodiment 26)；
(4) when using organic base, react also very poor (embodiment 27), even do not react (embodiment 28).
In addition, in embodiment 1 into embodiment 19, the inorganic base that we use is tert-butyl alcohol lithium salts, and reaction is almost quantitative
Occur, so tert-butyl alcohol lithium is optimal inorganic base.
In embodiment 1 into embodiment 28, the dosage of inorganic base and the dosage molar ratio of indoles are 3:1.Through experiment, nothing
The dosage of machine alkali and the dosage molar ratio of indoles can suitably be reduced to 1:1.
It can clearly find out that method using the present invention can be synthesized with high yield and high-purity by above-mentioned all embodiments
To 3- indoles seleno alcohol compounds, and reaction condition is mild, and reaction substrate scope is wide, and functional group's tolerance is good, post processing
Simply, it is easy to operate, it is suitble to large-scale industrial production, brand-new synthesis is provided for the efficient quick synthesis of such compound
Route.
Claims (8)
- The synthetic method of 1.3- indoles seleno alcohols organic compounds, which is characterized in that with Benzazole compounds and oxidation hexamethylene Alkene/cyclopentene oxide/1,2- epoxy butanes/methyloxetane/3,3- isobutylenes butane/2- furfuryl glycidols Ether is reaction substrate, using elemental selenium as selenium source, makees reaction dissolvent with water or organic solvent, when making reaction dissolvent with water, Xiang Shuizhong Phase transfer catalyst tetrabutylammonium iodide is added, it is no transition metal-catalyzed to obtain under the action of inorganic base in nitrogen atmosphere 3- indoles seleno alcohol compounds.
- 2. the synthetic method of 3- indoles seleno alcohols organic compound according to claim 1, which is characterized in that the list Matter selenium is selenium powder, and the dosage of the selenium powder and the dosage molar ratio of indoles are 1-3:1.
- 3. the synthetic method of 3- indoles seleno alcohols organic compound according to claim 1, which is characterized in that described to have Solvent is at least one of tetrahydrofuran, 1,4- dioxane, normal propyl alcohol and isopropanol.
- 4. the synthetic method of 3- indoles seleno alcohols organic compound according to claim 1, which is characterized in that the water Ratio with tetrabutylammonium iodide is 2mL:0.8mmol.
- 5. the synthetic method of 3- indoles seleno alcohols organic compound according to claim 1, which is characterized in that the nothing Machine alkali is potassium tert-butoxide, sodium tert-butoxide, tert-butyl alcohol lithium, sodium phosphate, potassium phosphate, cesium carbonate, potassium hydroxide, sodium hydroxide and pyrroles At least one of alkane.
- 6. the synthetic method of 3- indoles seleno alcohols organic compound according to claim 5, which is characterized in that the nothing The dosage of machine alkali and the dosage molar ratio of indoles are 1-3:1.
- 7. the synthetic method of 3- indoles seleno alcohols organic compound according to claim 1, which is characterized in that reaction temperature It spends for 20-60 DEG C, reaction time 6-16h.
- 8. the synthetic method of 3- indoles seleno alcohols organic compound according to claim 7, which is characterized in that reaction temperature It spends for 45 DEG C, reaction time 12h.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111253303A (en) * | 2020-03-21 | 2020-06-09 | 桂林医学院 | Method for synthesizing 3-selenium-spiro (2-cyclopentene-1, 3-indole) -4-ketone |
| CN115286555A (en) * | 2021-11-26 | 2022-11-04 | 温州医科大学 | Synthetic method of 3-alkynylselendole compound |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101117329A (en) * | 2006-08-04 | 2008-02-06 | 华东理工大学 | Synthesis of novel 3-seleno indole with vegetation promotion and selenium enriching functions |
| CN104370785A (en) * | 2014-12-03 | 2015-02-25 | 温州大学 | Synthetic method of Beta-hydroxyl selenide compound |
| CN107033048A (en) * | 2017-05-16 | 2017-08-11 | 温州医科大学 | A kind of synthetic method of aryl methyl selenide compound |
| CN107188841A (en) * | 2017-05-16 | 2017-09-22 | 温州医科大学 | A kind of synthetic method of asymmetric diaryl list selenide compound |
| CN107382803A (en) * | 2017-08-18 | 2017-11-24 | 温州大学 | A kind of preparation method of β hydroxy phenyls selenide compound |
-
2018
- 2018-01-10 CN CN201810023791.8A patent/CN108047118B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101117329A (en) * | 2006-08-04 | 2008-02-06 | 华东理工大学 | Synthesis of novel 3-seleno indole with vegetation promotion and selenium enriching functions |
| CN104370785A (en) * | 2014-12-03 | 2015-02-25 | 温州大学 | Synthetic method of Beta-hydroxyl selenide compound |
| CN107033048A (en) * | 2017-05-16 | 2017-08-11 | 温州医科大学 | A kind of synthetic method of aryl methyl selenide compound |
| CN107188841A (en) * | 2017-05-16 | 2017-09-22 | 温州医科大学 | A kind of synthetic method of asymmetric diaryl list selenide compound |
| CN107382803A (en) * | 2017-08-18 | 2017-11-24 | 温州大学 | A kind of preparation method of β hydroxy phenyls selenide compound |
Non-Patent Citations (3)
| Title |
|---|
| CHAO GAO ET AL.: "Copper-catalyzed three-component coupling reaction of azoles,se powder,and aryl iodides", 《J.ORG.CHEM.》 * |
| LIN MIN ET AL.: "Copper-catalyzed oxirane-opening reaction with aryl iodides and se powder", 《J.ORG.CHEM.》 * |
| 杨明华等: "氯化锌催化硒酚对环氧化合物开环反应合成β-羟基硒醚", 《催化学报》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111253303A (en) * | 2020-03-21 | 2020-06-09 | 桂林医学院 | Method for synthesizing 3-selenium-spiro (2-cyclopentene-1, 3-indole) -4-ketone |
| CN111253303B (en) * | 2020-03-21 | 2022-11-01 | 桂林医学院 | Method for synthesizing 3-selenium-spiro (2-cyclopentene-1,3-indole) -4-ketone |
| CN115286555A (en) * | 2021-11-26 | 2022-11-04 | 温州医科大学 | Synthetic method of 3-alkynylselendole compound |
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