CN108675948A - A kind of beta-hydroxy selenide compound and preparation method - Google Patents
A kind of beta-hydroxy selenide compound and preparation method Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C391/00—Compounds containing selenium
- C07C391/02—Compounds containing selenium having selenium atoms bound to carbon atoms of six-membered aromatic rings
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- 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
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- 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
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- C07D307/42—Singly bound oxygen atoms
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Abstract
The present invention relates to a kind of β hydroxyls selenide compound and preparation methods, in organic solvent, using epoxide and benzoic acid as reaction raw materials, using elemental selenium as seleno reagent, transition-metal catalyst silver and alkali collectively promote effect under, β hydroxyl selenide compounds are obtained by cascade reaction.The method reaction condition is simple, the yield of product and purity are high, has opened up new synthetic route and method for β hydroxyl selenide compounds, has had good application potential and researching value.
Description
Technical field
The invention belongs to organic compound synthesis technical fields, more particularly, to a kind of beta-hydroxy selenide compound and preparation
Method.
Background technology
So far, selenium element has been widely used in the synthesis of medicine, high molecular material, pesticide, such as develops more
A drug molecule containing selenide structure：Ebselen (ebselen) is Japanese first pharmacy and Nattermann companies of Germany
The novel anti-inflammatory medicine of exploitation, being currently in the clinical III phases studies；The D2EHDTPA of Tegafur with anti-tumor activity containing selenium
Ester type compound, the rhizoma et Radix Baphicacanthis Cusiae compound of polysaccharide of the selenizing inhibited to various tumor cell strains modification.Even agriculture
Industry field, wide spectrum is present in fungicide and herbicide selenide compound structure again, and be such as used as crops herbicide contains selenium three
Azoles amide.Largely scientific investigations showed that, selenium is the active constituent for constituting glutathione peroxidase, is inhibited as free radical
Agent effectively prevent beta Cell of islet Oxidative demage, promotes sugared part metabolism, reduces blood glucose and glucose in urine, improves the disease of diabetic
Shape, and the cysteine of needed by human body, methionine are also selenium-containing compound.
Several frequently seen drug molecule containing diaryliodonium
So important just because of the compound containing selenide structure, people, which synthesize it, has carried out numerous studies, especially
It is the synthesis to beta-hydroxy selenide compounds, has explored a plurality of synthetic route and method at present：
VG Ricordi in 2012 et al. (Preparation of the First Bench-Stable Phenyl
Selenolate：An Interesting " On Water " Nucleophilic Reagent.Eur.J.Org.Chem.2008,
It 5387-5390) reports phenyl selenium bromine compounds and simple substance zinc flows back in tetrahydrofuran solvent and obtains benzene selenium zinc metal reagent,
The ring-opening reaction that nucleopilic reagent benzene selenium anion as high activity participates in ethylene oxide obtains target product, and defect is that this is anti-
The benzene selenium bromine compounds starting material synthesized in requisition for previously prepared multistep, using a large amount of simple substance zinc, easy post-processing causes
The pollution of environment increases synthesis cost, and reaction equation is as follows：
2016, David J.Procter et al. (Convenient preparation of ytterbium (III)
chalcogenolate complexes by insertion of ytterbium into chalcogen-chalcogen
Bonds.Application in the ring-opening of epoxides.Tetrahedron Letters 2000,
41,4923-4927) diaryldiselenides are reported and form aryl selenium ytterbium metal reagent in anhydrous tetrahydro furan solvent with ytterbium,
The ring-opening reaction that ethylene oxide is participated in as active nucleopilic reagent obtains beta-hydroxy selenide compound, which is to make
With a large amount of rare earth metal ytterbium, easy post-processing causes the pollution of environment, reaction equation as follows：
Our seminars in 2016 are in (Copper-Catalyzed Oxirane-Opening Reaction with
Aryl Iodides and Se Powder.J.Org.Chem., 2016,81,7584-7590) report copper catalysis aryl iodate
Object, elemental selenium synthesize beta-hydroxy selenide with the cascade reaction of epoxyalkane, and reaction equation is as follows：
Although as it is above-mentioned and as it can be seen that exist in the prior art it is a variety of synthesis beta-hydroxy selenide derivatives preparation methods,
These methods mostly there is cumbersome, raw material need previously prepared, side reaction is more, condition is violent, functional group's tolerance is poor,
The narrow equal shortcomings of substrate spectrum.Therefore, for it is easy, be easily handled, raw material that substrate is cheap and easy to get prepares beta-hydroxy selenium
Ether derivant is particularly important, and beta-hydroxy is prepared especially with the one pot reaction of ethylene oxide, elemental selenium and benzoic acid
The reaction of selenide compound, is not reported so far, and there are still the necessity for continuing to study and explore, this is also that the present invention is able to
Where the basis of completion and power.
Invention content
Here, applicant is intended to explanation, the technical scheme is that in state natural sciences fund (number：
21602158) it is accomplished under subsidy, expresses thanks herein.
The problem of first technical problem to be solved by this invention is the synthetic route of beta-hydroxy selenide compound.
Second technical problem to be solved by this invention is beta-hydroxy selenide compound synthesis method functional group tolerance
The problem of.
Third technical problem to be solved by this invention is that beta-hydroxy selenide preparation of compounds is suitble to extensive work
The problem of industry metaplasia is produced.
In order to solve the above technical problems, the present invention provides following technical proposals：
A kind of beta-hydroxy selenide compound and preparation method, in organic solvent, to have the ring of the structure as shown in formula (I)
Oxygen compound and the benzoic acid of structure shown in formula (II) are that reaction raw materials are urged using elemental selenium as seleno reagent in transition metal
Collectively promoting under effect for agent silver and alkali, the beta-hydroxy selenide compound of structure shown in formula (III) is obtained by cascade reaction.
Above-mentioned reaction process can be indicated with following reaction equations：
The molar ratio of the epoxide of structure shown in (I) and the benzoic acid of structure shown in formula (II) is 1: 1-1: 5,
Preferably 1: 3；The molar ratio of the epoxide of structure and elemental selenium shown in (I) is 1: 1-1: 5, preferably 1: 3.
(1) epoxide
Epoxide in the present invention is cyclopentene oxide, 3,4- epoxies tetrahydrofuran, methyloxetane, tertiary butyl
Aoxidize cyclohexane, butadiene monoxide, 4- bromines styrene oxide, 2- chlorostyrene oxides and glycidol furfuryl ether.
(2) transition-metal catalyst silver
Transition-metal catalyst silver in the present invention is silver carbonate, silver acetate, silver oxide and silver sulfate；Preferably aoxidize
Silver, with molar amount, the dosage of the silver oxide is 0.1: 1-0.5: 1, preferably 0.1 with the formula (I) amount ratio.
(3) alkali
Alkali in the present invention is lithium carbonate, cesium carbonate, potassium carbonate, sodium carbonate, ammonium hydrogen carbonate, sodium acetate, lithium acetate, acetic acid
At least one of potassium, potassium phosphate, sodium phosphate, sodium tert-butoxide, potassium fluoride, sodium fluoride, tert-butyl alcohol lithium or potassium tert-butoxide, preferably uncle
Butanol lithium；With molar amount, dosage and the formula (I) amount ratio of the tert-butyl alcohol lithium are 1: 1-1: 5, preferably 1: 3.
(4) organic solvent
Reaction dissolvent in the present invention is organic solvent, and the organic solvent is dimethyl sulfoxide (DMSO), N, N- dimethyl formyls
Amine, polyethylene glycol, dichloromethane, ethyl acetate, pyridine, n-hexane, six alkane of Isosorbide-5-Nitrae-dioxy, 1,2- dichloroethanes, toluene, tetrahydrochysene
At least one of furans, methanol, ether, carbon tetrachloride, chloroform, n-butanol, preferably n,N-Dimethylformamide.
(5) reaction temperature
The present invention preparation method in, reaction temperature be 0-50 DEG C, may be, for example, in non-limiting manner 0 DEG C, 10 DEG C, 20 DEG C,
30 DEG C, 40 DEG C and 50 DEG C, preferably 30 DEG C of reaction temperature.
(6) reaction time
In the preparation process in accordance with the present invention, the reaction time, there is no particular limitation, such as can be detected by liquid chromatograph
The residual percentage of target product or raw material and determine suitable reaction time, it typically is 15-24 hours, it is non-limiting for example
It is 15 hours, 17 hours, 19 hours, 21 hours, 23 hours or 24 hours, preferably 24 hours reaction time.
(7) it isolates and purifies
The mixture of gained after reaction can be isolated and purified further, purer final products have been obtained.This
The field method well-known to the ordinarily skilled artisan isolated and purified, such as extraction may be used, column chromatography, distillation, filtering, centrifuge, wash
It washs, be fractionated and adsorb or at least two the methods of combination is isolated and purified, such as extraction, column chromatography.
The reaction mixture of acquisition can also be introduced directly into other processes directly reaction if necessary certainly to produce
Other products.Optionally, before being introduced into other processes, reaction mixture can be pre-processed, for example, concentration, extraction
Then one or more experimental implementations in taking and being evaporated under reduced pressure are introduced into other processes to obtain crude product or pure product.
In a preferred embodiment, post-processing step after reaction can be following method：After reaction,
Ethyl acetate filtering is added after reaction solution is cooled down, is concentrated under reduced pressure, (wherein silica gel is 300- by pillar layer separation by concentrate
400 mesh silica gel), using petroleum ether and ether body mixed liquor as eluant, eluent, eluent is collected, target product is obtained after concentration.
The preparation method of beta-hydroxy selenide compound provided by the invention has the advantages that：
A) reaction efficiently, high income, post-processing it is simple, easy to operate；
B) alkali, silver carbonate are cheap and easy to get；
C) using elemental selenium as seleno reagent；
D) reaction efficiency higher after reaction amplification.
The present invention be easy prepare the epoxide of structure as shown in (I) and the benzoic acid of structure shown in formula (II) be
Reaction raw materials, using elemental selenium as seleno reagent, under nitrogen reaction atmosphere, silver carbonate and alkali collectively promote effect under,
The beta-hydroxy selenide compound of structure shown in formula (III) is obtained by the reaction.Reaction condition, post-processing operation are simple, are suitble to extensive
Industrialized production.
Specific implementation mode
Below by specific embodiment, the present invention is described in detail, but the purposes of these exemplary embodiments and
Purpose is only used for enumerating the present invention, not constitutes any type of any restriction to the real protection scope of the present invention, more non-to incite somebody to action
Protection scope of the present 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- phenylseleno cyclopentanol compounds
At room temperature, by benzoic acid (1.2mmol, 3equiv), elemental selenium (1.2mmol, 3equiv), cyclopentene oxide
(0.4mmol, 1equiv), silver oxide (1.2mmol, 3equiv), tert-butyl alcohol lithium (1.2mmol, 3equiv) are added to reaction tube
In, it is then charged with nitrogen, and replace three times, under nitrogen reaction environment, it is anti-that 2mL n,N-Dimethylformamide is then added
Solvent is answered, is stirred for 24 hours under 30 DEG C of reaction temperatures.After reaction by thin-layer chromatography monitoring, reaction mixture is cooled down, so
Ethyl acetate is added afterwards to be diluted, the solution after dilution is transferred in separatory funnel, is extracted with saturated salt solution, is isolated
Water phase and organic phase, then water phase is extracted with ethyl acetate 3 times, merging organic phase, addition 5g anhydrous sodium sulfates, static 30min, often
It is secondary to wash filter cake totally 3 times with 5mL ethyl acetate, solvent is then spun off, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether:
Ether=98: 5), product is colourless liquid, yield 95%, products weight 92mg.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.58-7.55 (m, 2H), 7.28-7.26 (m, 3H), 4.18-4.15 (m, 1H),
3.42-3.38 (m, 1H), 2.30-2.23 (m, 1H), 2.09-2.03 (m, 1H), 1.82-1.60 (m, 5H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 134.20,129.36,129.11,127.48,79.06,49.29,32.90,
31.12 22.05；
It is as follows to the theoretical calculation and experimental result of product progress high resolution mass spectrum：
HRMS (EI, 70eV) calcd for C11H14OSe[M+]：265.0103 found 265.0101.
Embodiment 2
The synthesis of 3- hydroxyl -4- phenylseleno tetrahydrofuran-compounds
At room temperature, by benzoic acid (1.2mmol, 3equiv), elemental selenium (1.2mmol, 3equiv), 3,4- epoxy tetrahydrochysenes
Furans (0.4mmol, 1equiv), silver oxide (1.2mmol, 3equiv), tert-butyl alcohol lithium (1.2mmol, 3equiv) are added to instead
Ying Guanzhong is then charged with nitrogen, and replaces three times, and under nitrogen reaction environment, 2mL N, N- dimethyl formyls are then added
Amine reaction dissolvent stirs for 24 hours under 30 DEG C of reaction temperatures.After reaction by thin-layer chromatography monitoring, reaction mixture is cold
But, ethyl acetate is then added to be diluted, the solution after dilution is transferred in separatory funnel, is extracted with saturated salt solution,
Water phase and organic phase are isolated, then water phase is extracted with ethyl acetate 3 times, merges organic phase, 5g anhydrous sodium sulfates are added, it is static
30min washs filter cake totally 3 times with 5mL ethyl acetate every time, then spins off solvent, and product (elution is obtained through column chromatography for separation
Agent：Petroleum ether: ether=98: 5), product is colourless liquid, yield 81%, products weight 79mg.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.57-7.54 (m, 2H), 7.30-7.27 (m, 3H), 4.37-4.31 (m, 2H),
4.02 (dd, J1=4.5Hz, J2=9.5Hz, 1H), 3.77-3.72 (m, 2H), 3.63-3.60 (m, 1H), 2.63 (s, 1H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 134.1,129.4,128.7,127.9,77.8,74.0,72.2,47.4；
It is as follows to the theoretical calculation and experimental result of product progress high resolution mass spectrum：
HRMS (EI, 70eV)：calcd for C10H12O2Se[M+] 266.9896, found 266.9898.
Embodiment 3
The synthesis of 1- phenylseleno -2- methyl isopropyl alcoholic compounds
At room temperature, by benzoic acid (1.2mmol, 3equiv), elemental selenium (1.2mmol, 3equiv), methyloxetane
(0.4mmol, 1equiv), silver oxide (1.2mmol, 3equiv), tert-butyl alcohol lithium (1.2mmol, 3equiv) are added to reaction tube
In, it is then charged with nitrogen, and replace three times, under nitrogen reaction environment, it is anti-that 2mL n,N-Dimethylformamide is then added
Solvent is answered, is stirred for 24 hours under 30 DEG C of reaction temperatures.After reaction by thin-layer chromatography monitoring, reaction mixture is cooled down, so
Ethyl acetate is added afterwards to be diluted, the solution after dilution is transferred in separatory funnel, is extracted with saturated salt solution, is isolated
Water phase and organic phase, then water phase is extracted with ethyl acetate 3 times, merging organic phase, addition 5g anhydrous sodium sulfates, static 30min, often
It is secondary to wash filter cake totally 3 times with 5mL ethyl acetate, solvent is then spun off, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether:
Ether=98: 5), product is colourless liquid, yield 65%, products weight 60mg.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.56-7.54 (m, 2H), 7.26-7.23 (m, 3H), 3.15 (s, 2H), 2.26
(s, 1H), 1.31 (s, 6H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 132.5,130.9,129.2,127.0,70.4,44.4,29.0；
It is as follows to the theoretical calculation and experimental result of product progress high resolution mass spectrum：
HRMS：(EI, 70eV) calcd for C10H14OSe[M+] 253.0103, found 253.0106.
Embodiment 4
The synthesis of 1- phenylseleno -3,3- dimethyl isobutyryl alcoholic compounds
At room temperature, benzoic acid (1.2mmol, 3equiv), elemental selenium (1.2mmol, 3equiv), tertiary butyl are aoxidized into ring
Ethane (0.4mmol, 1equiv), silver oxide (1.2mmol, 3equiv), tert-butyl alcohol lithium (1.2mmol, 3equiv) are added to instead
Ying Guanzhong is then charged with nitrogen, and replaces three times, and under nitrogen reaction environment, 2mL N, N- dimethyl formyls are then added
Amine reaction dissolvent stirs for 24 hours under 30 DEG C of reaction temperatures.After reaction by thin-layer chromatography monitoring, reaction mixture is cold
But, ethyl acetate is then added to be diluted, the solution after dilution is transferred in separatory funnel, is extracted with saturated salt solution,
Water phase and organic phase are isolated, then water phase is extracted with ethyl acetate 3 times, merges organic phase, 5g anhydrous sodium sulfates are added, it is static
30min washs filter cake totally 3 times with 5mL ethyl acetate every time, then spins off solvent, and product (elution is obtained through column chromatography for separation
Agent：Petroleum ether: ether=98: 5), product is colourless liquid, yield 80%, products weight 82mg.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.52-7.50 (m, 2H), 7.27-7.25 (m, 3H), 3.27 (dd, J1=
11.0Hz J2=26.0Hz, 2H), 2.80 (t, J=12.0Hz, 1H), 2.49 (s, 1H), 0.92 (s, 9H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 132.9,129.4,129.2,127.2,77.1,34.9,33.3,25.8；
It is as follows to the theoretical calculation and experimental result of product progress high resolution mass spectrum：
HRMS (EI, 70eV)：calcd for C12H18OSe[M+] 281.0416, found 281.0417.
Embodiment 5
The synthesis of 1- (4- bromophenyls) -2- phenylseleno alcohol cpds
At room temperature, by benzoic acid (1.2mmol, 3equiv), elemental selenium (1.2mmol, 3equiv), 4- bromine Oxybenzene second
Alkene (0.4mmol, 1equiv), silver oxide (1.2mmol, 3equiv), tert-butyl alcohol lithium (1.2mmol, 3equiv) are added to reaction
Guan Zhong is then charged with nitrogen, and replaces three times, and under nitrogen reaction environment, 2mL n,N-Dimethylformamide is then added
Reaction dissolvent stirs for 24 hours under 30 DEG C of reaction temperatures.After reaction by thin-layer chromatography monitoring, reaction mixture is cooled down,
Then ethyl acetate is added to be diluted, the solution after dilution is transferred in separatory funnel, is extracted with saturated salt solution, is detached
Go out water phase and organic phase, then water phase is extracted with ethyl acetate 3 times, merging organic phase, addition 5g anhydrous sodium sulfates, static 30min,
Filter cake is washed with 5mL ethyl acetate totally 3 times, then spin off solvent, product (eluant, eluent is obtained through column chromatography for separation every time：Oil
Ether: ether=98: 5), product is colourless liquid, yield 72%, products weight 102mg.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.54-7.50 (m, 2H), 7.43 (d, J=8.0Hz, 2H), 7.29-7.27 (m,
3H), 7.19 (d, J=8.5Hz, 2H), 4.69-4.66 (m, 1H), 3.25 (dd, J1=3.5Hz, J2=12.5Hz, 1H), 3.06
(dd, J1=9.0Hz, J2=12.5Hz, 1H), 2.87 (d, J=3.0Hz, 1H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 141.5,133.3,131.6,129.4,128.8,127.6,127.6,
121.7,71.6,38.4；
It is as follows to the theoretical calculation and experimental result of product progress high resolution mass spectrum：
HRMS (EI, 70eV)：calcd for C14H13BrOSe[M+H]+356.9388 found 356.9390.
Embodiment 6
The synthesis of 1- (2- chlorphenyls) -2- phenylseleno alcohol cpds
At room temperature, by benzoic acid (1.2mmol, 3equiv), elemental selenium (1.2mmol, 3equiv), 2- oxychloride benzene second
Alkene (0.4mmol, 1equiv), silver oxide (1.2mmol, 3equiv), tert-butyl alcohol lithium (1.2mmol, 3equiv) are added to reaction
Guan Zhong is then charged with nitrogen, and replaces three times, and under nitrogen reaction environment, 2mL n,N-Dimethylformamide is then added
Reaction dissolvent stirs for 24 hours under 30 DEG C of reaction temperatures.After reaction by thin-layer chromatography monitoring, reaction mixture is cooled down,
Then ethyl acetate is added to be diluted, the solution after dilution is transferred in separatory funnel, is extracted with saturated salt solution, is detached
Go out water phase and organic phase, then water phase is extracted with ethyl acetate 3 times, merging organic phase, addition 5g anhydrous sodium sulfates, static 30min,
Filter cake is washed with 5mL ethyl acetate totally 3 times, then spin off solvent, product (eluant, eluent is obtained through column chromatography for separation every time：Oil
Ether: ether=98: 5), product is colourless liquid, yield 68%, products weight 85mg.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.64-7.56 (m, 3H), 7.29-7.17 (m, 6H), 5.12-5.09 (m, 1H),
3.47 (dd, J1=2.5Hz, J2=13.0Hz, 1H), 2.95 (dd, J1=9.5Hz, J2=13.0Hz, 1H), 2.92 (s, 1H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 139.8,133.2,131.7,129.4,129.2,128.8,128.7,
127.5,127.2,127.01,68.7,36.6；
It is as follows to the theoretical calculation and experimental result of product progress high resolution mass spectrum：
HRMS (EI, 70eV)：calcd for C14H13ClOSe[M+H]+312.9893 found 312.9890.
Embodiment 7
The synthesis of 1- (2- furanmethoxies) -3- phenylseleno isopropyl alcoholic compounds
At room temperature, by benzoic acid (1.2mmol, 3equiv), elemental selenium (1.2mmol, 3equiv), glycidol furfuryl ether
(0.4mmol, 1equiv), silver oxide (1.2mmol, 3equiv), tert-butyl alcohol lithium (1.2mmol, 3equiv) are added to reaction tube
In, it is then charged with nitrogen, and replace three times, under nitrogen reaction environment, it is anti-that 2mL n,N-Dimethylformamide is then added
Solvent is answered, is stirred for 24 hours under 30 DEG C of reaction temperatures.After reaction by thin-layer chromatography monitoring, reaction mixture is cooled down, so
Ethyl acetate is added afterwards to be diluted, the solution after dilution is transferred in separatory funnel, is extracted with saturated salt solution, is isolated
Water phase and organic phase, then water phase is extracted with ethyl acetate 3 times, merging organic phase, addition 5g anhydrous sodium sulfates, static 30min, often
It is secondary to wash filter cake totally 3 times with 5mL ethyl acetate, solvent is then spun off, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether:
Ether=98: 5), product is colourless liquid, yield 61%, products weight 76mg.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.52-7.50 (m, 2H), 7.39 (s, 1H), 7.26-7.24 (m, 3H), 6.34-
6.33 (m, 1H), 6.30-6.29 (m, 1H), 4.44 (s, 2H), 3.91-3.86 (m, 1H), 3.56 (dd, J1=4.0Hz, J2=
9.5Hz, 1H), 3.48 (dd, J1=6.0Hz, J2=9.5Hz, 1H), 3.06 (dd, J1=5.5Hz, J2=12.5Hz, 1H),
2.99 (dd, J1=7.0Hz, J2=12.5Hz, 1H), 2.61 (s, 1H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 151.4,142.9,132.8,129.6,129.2,127.2,110.3,
109.5,72.7,69.4,65.4,31.9；
It is as follows to the theoretical calculation and experimental result of product progress high resolution mass spectrum：
HRMS：(EI, 70eV) calcd for C14H16O3Se[M+] 335.0158, found 335.0155.
It can be seen that by above-described embodiment 1-7, when the method using the present invention, can be obtained with high yield, high-purity
To beta-hydroxy selenide compound.
Embodiment 8-10
In addition to transition-metal catalyst silver oxide therein is replaced with following silver salt respectively, with with highest product
The 1 identical mode of embodiment of yield and implement embodiment 8-10 respectively, the receipts of used silver salt compound and corresponding product
Rate is as shown in table 1 below.
Table 1
| Number | Silver salt | Reaction yield (%) |
| Embodiment 8 | Silver acetate | 47 |
| Embodiment 9 | Silver carbonate | 39 |
| Embodiment 10 | Silver sulfate | 45 |
It can be seen that by upper table 1, when using other silver salt, all react, but the yield decline of product is bigger, thus demonstrate,proves
Clear silver oxide is the successful key factor of the reaction, and maximally efficient to the reaction system.
Embodiment 11-24
In addition to alkali tert-butyl alcohol lithium therein is replaced with following inorganic base respectively, with the reality with highest products collection efficiency
It applies 1 identical mode of example and implements embodiment 11-24 respectively, yield such as the following table 2 of used alkali cpd and corresponding product
It is shown.
Table 2
| Number | Alkali | Reaction yield (%) |
| Embodiment 11 | Ammonium hydrogen carbonate | It does not react |
| Embodiment 12 | Lithium carbonate | It does not react |
| Embodiment 13 | Sodium carbonate | It does not react |
| Embodiment 14 | Cesium carbonate | It does not react |
| Embodiment 15 | Potassium phosphate | It does not react |
| Embodiment 16 | Sodium phosphate | It does not react |
| Embodiment 17 | Potassium carbonate | It does not react |
| Embodiment 18 | Sodium tert-butoxide | 77 |
| Embodiment 19 | Potassium tert-butoxide | 54 |
| Embodiment 20 | Sodium acetate | It does not react |
| Embodiment 21 | Lithium acetate | It does not react |
| Embodiment 22 | Potassium acetate | It does not react |
| Embodiment 23 | Potassium fluoride | It does not react |
| Embodiment 24 | Sodium fluoride | It does not react |
It can be seen that by upper table 2, when using other alkali, other than highly basic salt such as sodium tert-butoxide and potassium tert-butoxide, Ji Hujun
It does not react, it is the successful key factor of the reaction thus to demonstrate tert-butyl alcohol lithium, and maximally efficient to the reaction system.
Embodiment 25-39
In addition to organic solvent n,N-Dimethylformamide therein is replaced with following organic solvent respectively, with with
The 1 identical mode of embodiment of highest products collection efficiency and implement embodiment 25-39 respectively, used organic solvent and corresponding production
The yield of object is as shown in table 3 below.
Table 3
It can be seen that by upper table 3, when using other organic solvents, in addition to that can occur instead in intensive polar solvent dimethyl sulfoxide
It answers, but yield still decreases；And there is no spawn under the conditions of nonpolarity or even weak ligand solvent.This demonstrate that organic molten
Can the appropriately selected of agent carry out reaction significant, even conclusive influence.
In conclusion can clearly be found out by above-mentioned all embodiments, when method using the present invention is i.e. using selected from transition
Metallic catalyst (especially silver oxide), alkali (especially tert-butyl alcohol lithium) and suitable organic solvent (especially N, N- dimethyl
Formamide) formed recombination reaction system when, can make epoxide and elemental selenium, benzoic acid occur cascade reaction and with
High yield and high-purity synthesize to obtain beta-hydroxy selenide compound, for such compound efficient quick synthesis provide it is completely new
Synthetic route.
Finally it should be noted that：The above embodiments are only used to illustrate the technical solution of the present invention., rather than its limitations；To the greatest extent
Present invention has been described in detail with reference to the aforementioned embodiments for pipe, it will be understood by those of ordinary skill in the art that：Its according to
Technical scheme described in the above embodiments is modified for right scientific research, either to which part or all technical features into
Row equivalent replacement；And these modifications or replacements, various embodiments of the present invention technology that it does not separate the essence of the corresponding technical solution
The range of scheme.
Claims (8)
1. a kind of beta-hydroxy selenide compound and preparation method, which is characterized in that in organic solvent, to have such as formula (I) institute
The epoxide for showing structure and the benzoic acid of structure shown in formula (II) they are reaction raw materials, using elemental selenium as seleno reagent,
Collectively promoting under effect for transition-metal catalyst silver and alkali, the beta-hydroxy of structure shown in formula (III) is obtained by cascade reaction
Selenide compound.
2. preparation method as described in claim 1, which is characterized in that the transition-metal catalyst silver is silver carbonate, acetic acid
Silver, silver oxide or silver sulfate, preferably silver oxide.
3. preparation method as described in claim 1, which is characterized in that the alkali is silver carbonate, silver acetate, lithium carbonate, carbonic acid
Caesium, potassium carbonate, sodium carbonate, ammonium hydrogen carbonate, sodium acetate, lithium acetate, potassium acetate, potassium phosphate, sodium phosphate, sodium tert-butoxide, potassium fluoride,
Sodium fluoride, tert-butyl alcohol lithium or potassium tert-butoxide, preferably tert-butyl alcohol lithium.
4. preparation method according to claim 1, which is characterized in that the reaction dissolvent is organic solvent, described organic
Solvent is dimethyl sulfoxide (DMSO), n,N-Dimethylformamide, polyethylene glycol, dichloromethane, ethyl acetate, pyridine, n-hexane, Isosorbide-5-Nitrae-
At least one in six alkane of dioxy, 1,2- dichloroethanes, toluene, tetrahydrofuran, methanol, ether, carbon tetrachloride, chloroform, n-butanol
Kind, preferably n,N-Dimethylformamide.
5. preparation method according to claim 1, it is characterised in that：The epoxide and formula of structure shown in (I)
(II) molar ratio of the benzoic acid of structure shown in is 1: 1-1: 5；The epoxide of structure and rubbing for elemental selenium shown in (I)
You are than being 1: 1-1: 5；The molar ratio of the epoxide and alkali of structure shown in (I) is 1: 1-1: 5.
6. preparation method according to claim 1, which is characterized in that the temperature of the range is 0-50 DEG C.
7. preparation method according to claim 1, which is characterized in that the time of the reaction is 15-30h.
8. the preparation method of beta-hydroxy selenide compound as described in claim 1, it is characterised in that：It after reaction, will be anti-
It answers liquid cooling that extractant extraction is but added afterwards, isolates water phase and organic phase, the organic phase containing extractant and target product is taken to be used in combination
Anhydrous sodium sulfate is dried, and is concentrated under reduced pressure, by concentrate by pillar layer separation (wherein silica gel is 300-400 mesh silica gel), with stone
It is eluant, eluent that oily ether and ether volume ratio, which are 95: 5 mixed liquors, collects eluent, is obtained as shown in formula (III) after rotating solvent
Beta-hydroxy selenide compound.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111978229A (en) * | 2020-08-12 | 2020-11-24 | 温州医科大学 | Synthesis method of dialkyl diselenide compound |
| CN112250608A (en) * | 2020-10-26 | 2021-01-22 | 温州医科大学 | Synthetic method of 2-phenylacetylene selenol compound |
| CN112300043A (en) * | 2020-10-26 | 2021-02-02 | 温州医科大学 | Synthesis method of 1-arylacetylene seleno-3-phenoxy-2-propanol compound |
| CN112812047A (en) * | 2021-01-15 | 2021-05-18 | 南京理工大学 | Method for synthesizing alpha-seleno-alpha, beta-unsaturated carbonyl compound by using organic seleno sodium sulfate |
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2018
- 2018-05-04 CN CN201810445408.8A patent/CN108675948A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111978229A (en) * | 2020-08-12 | 2020-11-24 | 温州医科大学 | Synthesis method of dialkyl diselenide compound |
| CN112250608A (en) * | 2020-10-26 | 2021-01-22 | 温州医科大学 | Synthetic method of 2-phenylacetylene selenol compound |
| CN112300043A (en) * | 2020-10-26 | 2021-02-02 | 温州医科大学 | Synthesis method of 1-arylacetylene seleno-3-phenoxy-2-propanol compound |
| CN112812047A (en) * | 2021-01-15 | 2021-05-18 | 南京理工大学 | Method for synthesizing alpha-seleno-alpha, beta-unsaturated carbonyl compound by using organic seleno sodium sulfate |
| CN112812047B (en) * | 2021-01-15 | 2022-04-19 | 南京理工大学 | Method for synthesizing alpha-seleno-alpha, beta-unsaturated carbonyl compound by using organic seleno sodium sulfate |
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