CN108178741A - The synthetic method of β-alkynes seleno alcohols organic compound - Google Patents
The synthetic method of β-alkynes seleno alcohols organic compound Download PDFInfo
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- CN108178741A CN108178741A CN201810022619.0A CN201810022619A CN108178741A CN 108178741 A CN108178741 A CN 108178741A CN 201810022619 A CN201810022619 A CN 201810022619A CN 108178741 A CN108178741 A CN 108178741A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C391/00—Compounds containing selenium
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/40—Radicals substituted by oxygen atoms
- C07D307/42—Singly bound oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
Abstract
The invention discloses the synthetic methods of β alkynes seleno alcohols organic compounds, it is characterized in that, with terminal alkyne and cyclohexene oxide/1, the furfuryl glycidol ether of 2 epoxy butanes/methyloxetane/benzyl glycidyl ether/phenyl glycidyl ether/1 is reaction substrate, using elemental selenium as selenium source, reaction dissolvent is made with organic solvent, in nitrogen atmosphere, β alkynes seleno alcohols organic compounds are obtained under the action of inorganic base.The invention has the beneficial effects that：Method using the present invention can synthesize to obtain β alkynes seleno alcohols organic compounds with high yield and high-purity, and reaction condition is mild, reaction substrate range 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, the efficient quick synthesis for such compound provides completely new synthetic route.
Description
Technical field
The present invention relates to the synthetic methods of organic compound, and in particular to the synthesis side of β-alkynes seleno alcohols organic compound
Method belongs to organic compound synthesis technical field.
Background technology
Selenium is one of necessary beneficial trace element in organism, has a variety of special work(to health
Can, it is known as " kindling material of life " and " king of anticancer ".Selenium is present in nature in a variety of forms, and organic selenium compounds are one
The important existence form of kind.Since the eighties, with the synthesis of first organic selenium compounds ebselen, and find that it has
Anti-oxidant and neuroprotection effect, the development that Organic Selenium chemistry is leaped.
β-alkynes seleno alcohols organic compound is widely present in drug molecule, has good physiological activity, by new
Chemical constitution exploitation selenium-containing compound, become vital hot issue in the development of drug, therefore using a kind of new
Green synthesis method synthesis β-alkynes seleno alcohol compound have great significance in organic synthesis and pharmaceutical chemistry.
Due to the importance of β-alkynes seleno alcohol compound, people, which synthesize it, has carried out numerous studies, especially to alkynes
The synthesis of seleno compound has explored a plurality of synthetic route and method at present, such as：
(1) 2012 year, Braga et al. reported the side that alkynyl selenides are prepared with Terminal Acetylenes and diselenide in Tetrahedron
Method：
(2) 2012 years, Shanghai Institute of Organic Chemistry Chen Chao et al. has been delivered on J.Am.Chem.Soc. to be urged with elemental sulfur without metal
It is combined to the method for alkane alkynyl trifluoromethyl sulfide：
(3) 2015 years, Yuguang Wang et al. are reported on Org.Chem.Fron. to be joined with Terminal Acetylenes and trifluoromethyl
The method that copper pyridine prepares trifluoromethyl alkynyl selenides：
However, there is experimental implementation is cumbersome, noble metal is expensive, side reaction is more, reaction mostly for these synthetic methods
Many defects such as condition is violent, functional group's tolerance difference, also, they need first to synthesize the active intermediate kind containing selenium mostly,
Then it is reacted again with terminal alkyne compound.
Invention content
To solve the deficiencies in the prior art, the purpose of the present invention is to provide one kind is easy to operate, reaction condition is mild, production
The method that rate is high, functional group's tolerance is good, avoids synthesis β-alkynes seleno alcohols organic compound using noble metal.
In order to realize above-mentioned target, the present invention adopts the following technical scheme that：
The synthetic method of β-alkynes seleno alcohols organic compound, which is characterized in that with terminal alkyne and cyclohexene oxide/1,
2- epoxy butanes/methyloxetane/benzyl glycidyl ether/phenyl glycidyl ether/1- furfuryl glycidol ethers are
Reaction substrate using elemental selenium as selenium source, using organic solvent as reaction dissolvent, in nitrogen atmosphere, under the action of inorganic base, obtains
To β-alkynes seleno alcohols organic compound.
The synthetic method of aforementioned β-alkynes seleno alcohols organic compound, which is characterized in that aforementioned elemental selenium is selenium powder, preceding
It is 1-3 to state the dosage of selenium powder and the dosage molar ratio of terminal alkyne:1.
The synthetic method of aforementioned β-alkynes seleno alcohols organic compound, which is characterized in that aforementioned organic solvents for ethyl alcohol,
At least one of TBA, n-butanol, isopropanol, normal propyl alcohol, methanol, DMEA, tetrahydrofuran and Isosorbide-5-Nitrae-dioxane, preferably just
Propyl alcohol.
The synthetic method of aforementioned β-alkynes seleno alcohols organic compound, which is characterized in that aforementioned inorganic alkali is the tert-butyl alcohol
At least one of potassium, sodium tert-butoxide, potassium hydroxide, sodium hydroxide, sodium ethoxide and sodium methoxide, preferably potassium tert-butoxide.
The synthetic method of aforementioned β-alkynes seleno alcohols organic compound, which is characterized in that the dosage of aforementioned inorganic alkali with
The dosage molar ratio of terminal alkyne is 1-3:1, preferably 2:1.
The synthetic method of aforementioned β-alkynes seleno alcohols organic compound, which is characterized in that reaction temperature is 20-60 DEG C,
Reaction time is 6-16h, and preferable reaction temperature is 45 DEG C, reaction time 12h.
The invention has the beneficial effects that：
(1) reaction condition is mild, and elemental selenium is cheap and easy to get, and reaction substrate range 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) stench of diselenide in tradition reaction is avoided；
(4) metal catalytic necessary to being reacted without tradition.
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 reflected by nuclear magnetic resonance and high resolution mass spectrum
It is fixed.
Embodiment 1
The synthesis of 2- phenylacetylene seleno -1- cyclohexyl alcohols：
At room temperature, selenium powder (0.6mmol, 2equiv), potassium tert-butoxide (0.6mmol, 2equiv) are added to reaction tube
In, nitrogen is then taken out-rushes, displacement three times, in a nitrogen environment, adds in reaction dissolvent normal propyl alcohol (2mL) and reaction substrate benzene second
Alkynes (0.3mmol, 1equiv), cyclohexene oxide (0.9mmol, 3equiv), are then stirred at room temperature 2min and are uniformly mixed, then
It is stirred under 45 DEG C of reaction temperatures, reacts and terminate by thin-layer chromatography monitoring reaction course, after 12h.
With 10mL ethyl acetate diluted reaction mixtures, anhydrous sodium sulfate drying is then added in, is filtered after 5min, filter cake is used
Ethyl acetate washs (5mL × 3 time), then hangs solvent, product (eluant, eluent is obtained after column chromatography for separation：Petroleum ether：Acetic acid
Ethyl ester=8:1), product is yellow liquid, yield 88%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3)：δ 7.44-7.42 (m, 2H), 7.30 (t, J=3.2Hz, 3H), 3.69-3.64 (m,
1H),2.90-2.85(m,1H),2.73(s,1H),2.31-2.27(m,1H),2.19-2.15(m,1H),1.87-1.79(m,
2H),1.74-1.71(m,1H),1.41-1.30(m,3H)。
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,CDCl3)：δ131.6,128.3,128.3,123.4,101.4,72.7,67.7,53.4,
34.3,33.1,26.9,24.5。
The data of the high resolution mass spectrum of products therefrom are as follows：
HRMS(TIC)：calcd for C14H16OSeNa[M+Na]+303.0264,found303.0259。
As it can be seen that products therefrom is 2- phenylacetylene seleno -1- cyclohexyl alcohols.
Embodiment 2
The synthesis of 2- (4- methyl phenylacetylenes seleno) -1- cyclohexyl alcohols：
At room temperature, selenium powder (0.6mmol, 2equiv), potassium tert-butoxide (0.6mmol, 2equiv) are added to reaction tube
In, nitrogen is then taken out-rushes, displacement three times, in a nitrogen environment, adds in reaction dissolvent normal propyl alcohol (2mL) and reaction substrate oxidation
Cyclohexene (0.9mmol, 3equiv) is then stirred at room temperature 2min and is uniformly mixed, then stirs 6h under 45 DEG C of reaction temperatures,
It is added in later with syringe to methyl phenylacetylene (0.3mmol, 1equiv), it is anti-after 6h by thin-layer chromatography monitoring reaction course
It should terminate.
With 10mL ethyl acetate diluted reaction mixtures, anhydrous sodium sulfate drying is then added in, is filtered after 5min, filter cake is used
Ethyl acetate washs (5mL × 3 time), then hangs solvent, product (eluant, eluent is obtained after column chromatography for separation：Petroleum ether：Acetic acid
Ethyl ester=8:1), product is yellow liquid, yield 82%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3)：δ 7.32 (d, J=7.95Hz, 2H), 7.11 (d, J=7.95Hz, 2H), 3.69-
3.64(m,1H),2.89-2.84(m,1H),2.69(s,1H),2.34(s,3H),2.32-2.26(m,1H),2.21-2.14(m,
1H),1.86-1.71(m,3H),1.41-1.30(m,3H)。
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,CDCl3)：δ138.5,131.6,129.1,120.4,101.5,72.7,66.5,53.4,
34.3,33.1,26.8,24.5,21.5。
The data of the high resolution mass spectrum of products therefrom are as follows：
HRMS(TIC)：calcd for C15H19OSe[M+H]+295.0596,found295.0571。
As it can be seen that products therefrom is 2- (4- methyl phenylacetylenes seleno) -1- cyclohexyl alcohols.
Embodiment 3
The synthesis of 2- (the chloro- phenylacetylene selenos of 4-) -1- cyclohexyl alcohols：
At room temperature, selenium powder (0.6mmol, 2equiv), potassium tert-butoxide (0.6mmol, 2equiv) are added to reaction tube
In, nitrogen is then taken out-rushes, displacement three times, in a nitrogen environment, adds in reaction dissolvent normal propyl alcohol (2mL) and reaction substrate oxidation
Cyclohexene (0.9mmol, 3equiv) is then stirred at room temperature 2min and is uniformly mixed, then stirs 6h under 45 DEG C of reaction temperatures,
It is added in chlorobenzene acetylene (0.3mmol, 1equiv) with syringe, by thin-layer chromatography monitoring reaction course, is reacted after 6h later
Terminate.
With 10mL ethyl acetate diluted reaction mixtures, anhydrous sodium sulfate drying is then added in, is filtered after 5min, filter cake is used
Ethyl acetate washs (5mL × 3 time), then hangs solvent, product (eluant, eluent is obtained after column chromatography for separation：Petroleum ether：Acetic acid
Ethyl ester=8:1), product is yellow liquid, yield 89%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3)：δ7.37-7.32(m,2H),7.30-7.27(m,2H),3.71-3.63(m,1H),
2.97-2.87(m,1H),2.62(s,1H),2.30-2.17(m,2H),1.90-1.70(m,3H),1.48-1.31(m,3H)。
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,CDCl3)：δ134.3,132.8,128.6,121.9,100.2,72.8,69.1,53.5,
34.4,33.1,26.8,24.5。
The data of the high resolution mass spectrum of products therefrom are as follows：
HRMS(TIC)：calcd for C14H15ClOSeNa[M+Na]+336.9875,found336.9871。
As it can be seen that products therefrom is 2- (the chloro- phenylacetylene selenos of 4-) -1- cyclohexyl alcohols.
Embodiment 4
The synthesis of 2- (naphthalene -1- acetylene seleno) -1- cyclohexyl alcohols：
At room temperature, selenium powder (0.6mmol, 2equiv), potassium tert-butoxide (0.6mmol, 2equiv) are added to reaction tube
In, nitrogen is then taken out-rushes, displacement three times, in a nitrogen environment, adds in reaction dissolvent normal propyl alcohol (2mL) and reaction substrate 1- naphthalenes
Acetylene (0.3mmol, 1equiv), cyclohexene oxide (0.9mmol, 3equiv), are then stirred at room temperature 2min and are uniformly mixed,
It is stirred under 45 DEG C of reaction temperatures again, reacts and terminate by thin-layer chromatography monitoring reaction course, after 12h.
With 10mL ethyl acetate diluted reaction mixtures, anhydrous sodium sulfate drying is then added in, is filtered after 5min, filter cake is used
Ethyl acetate washs (5mL × 3 time), then hangs solvent, product (eluant, eluent is obtained after column chromatography for separation：Petroleum ether：Acetic acid
Ethyl ester=8:1), product is yellow liquid, yield 85%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3)：δ 8.30 (d, J=8.5Hz, 1H), 7.83-7.78 (m, 2H), 7.66 (d, J=
8.0Hz, 1H), 7.56 (t, J=8.0Hz, 1H), 7.49 (t, J=8.0Hz, 1H), 7.39 (t, J=8.0Hz), 3.75 (m,
1H),2.93(m,1H),2.81(s,1H),2.36-2.32(m,1H),2.20-2.16(m,1H),1.96-1.87(m,1H),
1.81-1.71(m,2H),1.42-1.30(m,3H)。
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,CDCl3)：δ133.4,133.2,130.5,128.7,128.3,126.8,126.4,
126.1,125.1,121.1,99.5,72.8,72.6,53.6,34.5,33.3,26.9,24.5。
The data of the high resolution mass spectrum of products therefrom are as follows：
HRMS(TIC)：calcd for C18H19OSe[M+H]+331.0596,found331.0589。
As it can be seen that products therefrom is 2- (naphthalene -1- acetylene seleno) -1- cyclohexyl alcohols.
Embodiment 5
The synthesis of 2- (thienyl -3- acetylene seleno) -1- cyclohexyl alcohols：
At room temperature, selenium powder (0.6mmol, 2equiv), potassium tert-butoxide (0.6mmol, 2equiv) are added to reaction tube
In, nitrogen is then taken out-rushes, displacement three times, in a nitrogen environment, adds in reaction dissolvent normal propyl alcohol (2mL) and reaction substrate oxidation
Cyclohexene (0.9mmol, 3equiv) is then stirred at room temperature 2min and is uniformly mixed, then stirs 6h under 45 DEG C of reaction temperatures,
3- thiophene acetylene (0.3mmol, 1equiv) is added in syringe later, by thin-layer chromatography monitoring reaction course, is reacted after 6h
Terminate.
With 10mL ethyl acetate diluted reaction mixtures, anhydrous sodium sulfate drying is then added in, is filtered after 5min, filter cake is used
Ethyl acetate washs (5mL × 3 time), then hangs solvent, product (eluant, eluent is obtained after column chromatography for separation：Petroleum ether：Acetic acid
Ethyl ester=6:1), product is yellow liquid, yield 84%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3)：δ 7.48-7.44 (m, 1H), 7.27-7.25 (m, 1H), 7.12-7.11 (d, J=
5.0Hz,1H),3.70-3.63(m,1H),2.89-2.84(m,1H),2.65(s,1H),2.29-2.16(m,2H),1.85-
1.72(m,3H),1.41-1.31(m,3H)。
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,CDCl3)：δ130.0,129.3,125.2,122.5,96.1,72.8,67.1,53.5,
34.3,33.1,26.8,24.5。
The data of the high resolution mass spectrum of products therefrom are as follows：
HRMS(TIC)：calcd for C12H14OSSeNa[M+Na]+308.9829,found308.9826。
As it can be seen that products therefrom is 2- (thienyl -3- acetylene seleno) -1- cyclohexyl alcohols.
Embodiment 6
The synthesis of 1- (phenylacetylene seleno) -2- butanol：
At room temperature, selenium powder (0.6mmol, 2equiv), potassium tert-butoxide (0.6mmol, 2equiv) are added to reaction tube
In, nitrogen is then taken out-rushes, displacement three times, in a nitrogen environment, adds in reaction dissolvent normal propyl alcohol (2mL) and reaction substrate benzene second
Alkynes (0.3mmol, 1equiv), 1,2- epoxy butanes (0.9mmol, 3equiv), are then stirred at room temperature 2min and are uniformly mixed,
It is stirred under 45 DEG C of reaction temperatures again, reacts and terminate by thin-layer chromatography monitoring reaction course, after 12h.
With 10mL ethyl acetate diluted reaction mixtures, anhydrous sodium sulfate drying is then added in, is filtered after 5min, filter cake is used
Ethyl acetate washs (5mL × 3 time), then hangs solvent, product (eluant, eluent is obtained after column chromatography for separation：Petroleum ether：Acetic acid
Ethyl ester=8:1), product is yellow liquid, yield 92%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3)：δ7.42-7.40(m,2H),7.31-7.29(m,3H),3.93-3.89(m,1H),
3.12(dd,J1=3.5Hz, J2=12.5Hz, 1H), 2.83 (dd, J1=8.5Hz, J2=12.5Hz, 1H), 2.37 (s, 1H),
1.69-1.60 (m, 2H), 1.01 (t, J=7.5Hz, 3H).
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,CDCl3)：δ131.6,128.3,123.3,99.2,72.0,69.5,37.3,29.4,
10.1。
The data of the high resolution mass spectrum of products therefrom are as follows：
HRMS(TIC)：calcd for C13H22OSeNa[M+Na]+277.0108,found277.0109。
As it can be seen that products therefrom is 1- (phenylacetylene seleno) -2- butanol.
Embodiment 7
The synthesis of 2- methyl-1s-phenylacetylene seleno -2- propyl alcohol：
At room temperature, selenium powder (0.6mmol, 2equiv), potassium tert-butoxide (0.6mmol, 2equiv) are added to reaction tube
In, nitrogen is then taken out-rushes, displacement three times, in a nitrogen environment, adds in reaction dissolvent normal propyl alcohol (2mL) and reaction substrate benzene second
Alkynes (0.3mmol, 1equiv), methyloxetane (0.9mmol, 3equiv), are then stirred at room temperature 2min and are uniformly mixed,
It is stirred under 45 DEG C of reaction temperatures again, by thin-layer chromatography monitoring reaction course, after 12h after reaction.
With 10mL ethyl acetate diluted reaction mixtures, anhydrous sodium sulfate drying is then added in, is filtered after 5min, filter cake is used
Ethyl acetate washs (5mL × 3 time), then hangs solvent, product (eluant, eluent is obtained after column chromatography for separation：Petroleum ether：Acetic acid
Ethyl ester=8:1), product is yellow liquid, yield 91%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3)：δ7.47-7.38(m,2H),7.34-7.27(m,3H),3.10(s,2H),2.16
(s,1H),1.42(s,6H)。
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,CDCl3)：δ131.5,128.3,128.2,123.3,98.4,71.1,71.0,44.9,
28.9。
The data of the high resolution mass spectrum of products therefrom are as follows：
HRMS(TIC)：calcd for C13H22OSeNa[M+Na]+277.0108,found277.0109.
As it can be seen that products therefrom is 2- methyl-1s-phenylacetylene seleno -2- propyl alcohol.
Embodiment 8
The synthesis of 1- benzyloxy -3- phenylacetylene seleno -2- propyl alcohol：
At room temperature, selenium powder (0.6mmol, 2equiv), potassium tert-butoxide (0.6mmol, 2equiv) are added to reaction tube
In, nitrogen is then taken out-rushes, displacement three times, in a nitrogen environment, adds in reaction dissolvent normal propyl alcohol (2mL) and reaction substrate benzene second
It is equal that 2min mixing is then stirred at room temperature in alkynes (0.3mmol, 1equiv), benzyl glycidyl ether (0.9mmol, 3equiv)
It is even, then stirred under 45 DEG C of reaction temperatures, it reacts and terminates by thin-layer chromatography monitoring reaction course, after 12h.
With 10mL ethyl acetate diluted reaction mixtures, anhydrous sodium sulfate drying is then added in, is filtered after 5min, filter cake is used
Ethyl acetate washs (5mL × 3 time), then hangs solvent, product (eluant, eluent is obtained after column chromatography for separation：Petroleum ether：Acetic acid
Ethyl ester=6:1), product is yellow liquid, yield 70%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3)：δ7.39-7.37(m,2H),7.37-7.23(m,8H),4.55(s,2H),4.18-
4.14(m,1H),3.65(dd,J1=4.0Hz, J2=9.5Hz, 1H), 3.60 (dd, J1=6.0Hz, J2=9.5Hz, 1H),
3.03(dd,J1=6.0Hz, J2=12.5Hz, 1H), 2.97 (dd, J1=7.0Hz, J2=12.5Hz, 1H), 2.82 (s, 1H).
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,CDCl3)：δ137.7,131.6,128.5,128.3,128.2,127.8,127.8,
123.3,99.3,73.5,72.7,69.9,69.7,33.1。
The data of the high resolution mass spectrum of products therefrom are as follows：
HRMS(TIC)：calcd for C18H18O2SeNa[M+Na]+369.0370,found369.0371。
As it can be seen that products therefrom is 1- benzyloxy -3- phenylacetylene seleno -2- propyl alcohol.
Embodiment 9
The synthesis of 1- (furyl -2- methoxyl groups) -3- phenylacetylene seleno -2- propyl alcohol：
At room temperature, selenium powder (0.6mmol, 2equiv), potassium tert-butoxide (0.6mmol, 2equiv) are added to reaction tube
In, nitrogen is then taken out-rushes, displacement three times, in a nitrogen environment, adds in reaction dissolvent normal propyl alcohol (2mL) and reaction substrate benzene second
Alkynes (0.3mmol, 1equiv), 1- furfuryls glycidol ether (0.9mmol, 3equiv), are then stirred at room temperature 2min
It is uniformly mixed, then is stirred under 45 DEG C of reaction temperatures, react and terminate by thin-layer chromatography monitoring reaction course, after 12h.
With 10mL ethyl acetate diluted reaction mixtures, anhydrous sodium sulfate drying is then added in, is filtered after 5min, filter cake is used
Ethyl acetate washs (5mL × 3 time), then hangs solvent, product (eluant, eluent is obtained after column chromatography for separation：Petroleum ether：Acetic acid
Ethyl ester=4:1), product is yellow liquid, yield 87%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3)：δ7.43-7.35(m,3H),7.32-7.25(m,3H),6.32-6.30(m,2H),
4.50(s,2H),4.13(s,1H),3.66-3.64(m,1H),3.60-3.54(m,1H),3.04-3.01(m,1H),2.97-
2.93(m,1H),2.86(s,1H)。
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,CDCl3)：δ151.3,142.9,131.6,128.3,128.2,123.3,110.3,
109.6,99.3,72.5,70.0,69.7,65.2,32.9。
The data of the high resolution mass spectrum of products therefrom are as follows：
HRMS(TIC)：calcd for C16H16O3SeNa[M+Na]+359.0163,found359.0174。
As it can be seen that products therefrom is 1- (furyl -2- methoxyl groups) -3- phenylacetylene seleno -2- propyl alcohol.
Embodiment 10
The synthesis of 1- phenoxy group -3- phenylacetylene seleno -2- propyl alcohol：
At room temperature, selenium powder (0.6mmol, 2equiv)/potassium tert-butoxide (0.6mmol, 2equiv) is added to reaction tube
In, nitrogen is then taken out-rushes, displacement three times, in a nitrogen environment, adds in reaction dissolvent normal propyl alcohol (2mL) and reaction substrate benzene second
It is equal that 2min mixing is then stirred at room temperature in alkynes (0.3mmol, 1equiv), phenyl glycidyl ether (0.9mmol, 3equiv)
It is even, then stirred under 45 DEG C of reaction temperatures, it reacts and terminates by thin-layer chromatography monitoring reaction course, after 12h.
With 10mL ethyl acetate diluted reaction mixtures, anhydrous sodium sulfate drying is then added in, is filtered after 5min, filter cake is used
Ethyl acetate washs (5mL × 3 time), then hangs solvent, product (eluant, eluent is obtained after column chromatography for separation：Petroleum ether：Acetic acid
Ethyl ester=6:1), product is yellow liquid, yield 95%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR(500MHz,CDCl3)：δ7.38-7.33(m,2H),7.29-7.22(m,5H),6.97-6.90(m,3H),
4.10-4.31(m,1H),4.16-4.10(m,2H),3.17(dd,J1=5.5Hz, J2=12.5Hz, 1H), 3.07 (dd, J1=
7.0Hz,J2=12.5Hz, 1H), 2.89 (s, 1H).
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,CDCl3)：δ158.3,131.6,129.5,128.3,128.3,123.1,121.3,
114.6,99.6,70.3,69.6,69.5,32.8。
The data of the high resolution mass spectrum of products therefrom are as follows：
HRMS(TIC)：calcd for C17H16O2SeNa[M+Na]+355.0214,found355.0215。
As it can be seen that products therefrom is 1- phenoxy group -3- phenylacetylene seleno -2- propyl alcohol.
In embodiment 1 to embodiment 10, reaction dissolvent we select be normal propyl alcohol.Through experiment, reaction dissolvent in addition to
Other than normal propyl alcohol, the organic solvents such as alcohol, ether, chloralkane, aromatic hydrocarbon, ester, heterocyclic arene, aliphatic hydrocarbon can also be selected, 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, including 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 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 ethyl acetate, pyridine, n-hexane can also be used as the reaction dissolvent of the present invention.
Embodiment 11 is to embodiment 27
Other than reaction dissolvent difference, embodiment 11 to embodiment 27 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：
As seen from the above table：
(1) when using protonic solvent, reaction yield is higher, and it is molten to do reaction especially with the alcohol containing active hydrogen
Agent, wherein, it is reacted in normal propyl alcohol best (embodiment 1), separation yield reaches 88%；
(2) when using other aprotic solvent, reaction is very poor, does not react even.
Consider, normal propyl alcohol is best reaction dissolvent.
In embodiment 1 to embodiment 10, inorganic base we select be potassium tert-butoxide.Through experiment, sodium tert-butoxide, hydrogen-oxygen
Change all alternative potassium tert-butoxide application of potassium, sodium hydroxide, sodium acetate in the present invention.
Embodiment 28 is to embodiment 44
Other than inorganic base difference, embodiment 28 to embodiment 44 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) inorganic weak bases, middle highly basic and organic base cannot all be catalyzed reaction, not react even well；
(2) only under the effect of the inorganic strong alkalis such as stronger potassium hydroxide, sodium hydroxide, potassium tert-butoxide, sodium tert-butoxide,
Reaction could carry out well.
Consider, potassium tert-butoxide is best inorganic base.
In embodiment 1 to embodiment 44：
1st, the dosage of inorganic base and the dosage molar ratio of terminal alkyne are 3:1.Through experiment, the dosage of inorganic base and end
The dosage molar ratio of alkynes can suitably be reduced to 1:1；
2nd, the dosage of selenium powder and the dosage molar ratio of terminal alkyne are 3:1.Through experiment, the dosage of selenium powder and terminal alkyne
Dosage molar ratio can suitably be reduced to 1:1；
3rd, reaction temperature is 45 DEG C, reaction time 12h.Through experiment, reaction temperature can be appropriate in the range of 20-60 DEG C
It adjusts, correspondingly, the reaction time can suitably adjust in the range of 6-16h.
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 β-alkynes seleno alcohols organic compound, and reaction condition is mild, and reaction substrate range is wide, and functional group's tolerance is good, rear to locate
Reason is simple, easy to operate, is suitble to large-scale industrial production, and the efficient quick synthesis for such compound provides completely new conjunction
Into route.
Claims (9)
1. the synthetic method of β-alkynes seleno alcohols organic compound, which is characterized in that with terminal alkyne and cyclohexene oxide/1,2-
Epoxy butane/methyloxetane/benzyl glycidyl ether/phenyl glycidyl ether/1- furfuryl glycidol ethers are anti-
Substrate is answered, using elemental selenium as selenium source, using organic solvent as reaction dissolvent, in nitrogen atmosphere, under the action of inorganic base, is obtained
β-alkynes seleno alcohols organic compound.
2. the synthetic method of β according to claim 1-alkynes seleno alcohols organic compound, which is characterized in that the simple substance
Selenium is selenium powder, and the dosage of the selenium powder and the dosage molar ratio of terminal alkyne are 1-3:1.
3. the synthetic method of β according to claim 1-alkynes seleno alcohols organic compound, which is characterized in that described organic
Solvent be ethyl alcohol, TBA, n-butanol, isopropanol, normal propyl alcohol, methanol, DMEA, tetrahydrofuran and 1,4- dioxane at least
It is a kind of.
4. the synthetic method of β according to claim 3-alkynes seleno alcohols organic compound, which is characterized in that the reaction
Solvent is normal propyl alcohol.
5. the synthetic method of β according to claim 1-alkynes seleno alcohols organic compound, which is characterized in that described inorganic
Alkali is at least one of potassium tert-butoxide, sodium tert-butoxide, potassium hydroxide, sodium hydroxide, sodium ethoxide and sodium methoxide.
6. the synthetic method of β according to claim 5-alkynes seleno alcohols organic compound, which is characterized in that described inorganic
Alkali is potassium tert-butoxide.
7. the synthetic method of β according to claim 5-alkynes seleno alcohols organic compound, which is characterized in that described inorganic
The dosage of alkali and the dosage molar ratio of terminal alkyne are 1-3:1.
8. the synthetic method of β according to claim 1-alkynes seleno alcohols organic compound, which is characterized in that reaction temperature
It is 20-60 DEG C, reaction time 6-16h.
9. the synthetic method of β according to claim 8-alkynes seleno alcohols organic compound, which is characterized in that reaction temperature
It is 45 DEG C, reaction time 12h.
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