CN107382803B - A kind of preparation method of beta-hydroxy phenyl selenide compound - Google Patents
A kind of preparation method of beta-hydroxy phenyl selenide compound Download PDFInfo
- Publication number
- CN107382803B CN107382803B CN201710711250.XA CN201710711250A CN107382803B CN 107382803 B CN107382803 B CN 107382803B CN 201710711250 A CN201710711250 A CN 201710711250A CN 107382803 B CN107382803 B CN 107382803B
- Authority
- CN
- China
- Prior art keywords
- beta
- copper
- hydroxy phenyl
- preparation
- silver
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Epoxy Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to organic compound synthesis technical fields, more particularly, to a kind of preparation method of beta-hydroxy phenyl selenide compound.A kind of preparation method of beta-hydroxy phenyl selenide compound, using fragrant boric acid, elemental selenium and the epoxyethane derivative as shown in formula (II) with the structure as shown in formula (I) as raw material, under the collective effect of copper catalyst, silver salt and alkali, the intercalation reaction in reaction dissolvent through elemental selenium obtains the beta-hydroxy phenyl selenide compound as shown in formula (III);In formula (I), formula (II) and formula (III), R1、R2It is each independently selected from one of H, phenyl ring, naphthalene nucleus, heterocycle, substituted benzene ring, straight chained alkyl, branched alkyl, halogen, nitro and cyano.
Description
Technical field
The present invention relates to organic compound synthesis technical fields, more particularly, to a kind of beta-hydroxy phenyl selenide compound
Preparation method.
Background technique
2010, Sangit Kumar et al. under copper catalysis, synthesized Ebselen with simple substance Se powder in the molecule, the
Primary report Se powder participates in catalytic cycle process, and constructs Se-N synthetic reaction for the first time.The method has used one kettle way, and before
Method compare, greatly reduce experimental procedure.It is higher but there are temperature, the disadvantages of functional group compatibility is bad.Reaction equation
It is as follows:
2014, Jin Tao Yu et al. phenyl boric acid and simple substance Se synthesized symmetrical single selenide under copper catalysis.But
It is that substrate universality is poor, is only applicable to the phenyl boric acid of general electron substituent group.
2015, Kumara et al., six, seven member ring heterocyclic compounds object was synthesized in the molecule under CuI catalysis with simple substance Se.
The method regioselectivity is good, and has used 1.5eq water, provides reference to Se reaction is further inserted.
Generally speaking, transition metal-catalyzed that organic selenium class compound is synthesized based on the reaction of the slotting selenium of aromatic yl reagent-ing
Research is an in the ascendant and vigorous research frontier, and it is numerous that quasi- research method overcomes prior synthesizing method step
Trivial, severe reaction conditions, functional group compatibility difference and starting material are not easy the disadvantages of obtaining, and not only have important theoretical value
Also there is potential application prospect simultaneously.Therefore, the slotting selenium reaction of transition metal-catalyzed aromatic yl reagent-ing is studied, and passes through observation
The experimental phenomena arrived and true further discussion reaction mechanism, then carry out on the basis of above and insert selenium reactive intermediate ginseng
To a variety of tandem reactions and related drug containing selenium and functional material synthesis in application be very necessary
Summary of the invention
Goal of the invention: the present invention has made improvements in view of the above-mentioned problems of the prior art, i.e., the invention discloses one kind
The preparation method of beta-hydroxy phenyl selenide compound.
Technical solution: a kind of preparation method of beta-hydroxy phenyl selenide compound, with the virtue with the structure as shown in formula (I)
Boric acid, elemental selenium and the epoxyethane derivative as shown in formula (II) are raw material, in the collective effect of copper catalyst, silver salt and alkali
Under, the intercalation reaction in reaction dissolvent through elemental selenium obtains the beta-hydroxy phenyl selenide compound as shown in formula (III);
In formula (I), formula (II) and formula (III), R1、R2Be each independently selected from H, phenyl ring, naphthalene nucleus, heterocycle, substituted benzene ring,
One of straight chained alkyl, branched alkyl, halogen, nitro and cyano.
Further, copper catalyst is organic copper or inorganic copper compound, and with molar amount, the dosage of copper catalyst is institute
State the 1~10% of fragrant boric acid dosage.
Further, Inorganic Copper be copper halide, cuprous halide, Cu oxide, elemental copper, copper inorganic salts at least
One kind, preferably copper chloride;
Organic copper is at least one of acetylacetone copper, copper acetate, cuprous acetate, three fluosulfonic acid copper, cuprous sulfocyanide.
Further, copper catalyst CuO, CuI, CuBr, CuCl, Cu (OTf)2、Cu(acac)2、(Cu(OAc)2, copper
Powder, CuSCN, CuF2、CuSO4、CuOAc、CuCl2、Cu2At least one of O, preferably CuCl2;With molar amount, the copper is urged
The dosage of agent is the 1-10% of the fragrant boric acid dosage.
Further, silver salt be silver oxide, silver nitrate, silver carbonate, silver acetate, silver sulfate, silver tetrafluoroborate, silver bromide,
At least one of silver hexafluoroantimonate, silver trifluoromethanesulfonate, preferably silver nitrate;With molar amount, the dosage of the silver salt and institute
The amount ratio for stating fragrant boric acid is 1:(0.5~2).
Further, alkali is potassium tert-butoxide, the tert-butyl alcohol is received, potassium carbonate, sodium carbonate, sodium ethoxide, sodium methoxide, potassium fluoride, fluorine
Change caesium, potassium hydroxide, sodium hydroxide, sodium hydride, sodium phosphate, potassium phosphate, sodium acetate, cesium carbonate, ammonium sulfate, in Potassiumiodate extremely
Few one kind, preferably potassium tert-butoxide;With molar amount, the amount ratio of the dosage of the alkali and the fragrant boric acid is 1:(0.5~2).
Further, reaction dissolvent is organic solvent, the organic solvent be alcohol, ether, amide, chloralkane, aromatic hydrocarbon,
At least one of dimethyl sulfoxide, ester, heterocyclic arene, aliphatic hydrocarbon.
Further, reaction dissolvent is organic solvent, and the organic solvent is dimethyl sulfoxide, N, N- dimethyl formyl
Amine, ethyl alcohol, polyethylene glycol, methylene chloride, ethyl acetate, pyridine, n-hexane, 1,4- dioxane, 1,2- dichloroethanes, first
Benzene, tetrahydrofuran, methanol, ether, carbon tetrachloride, dimethylbenzene, benzene, chloroform, normal propyl alcohol, isopropanol, at least one in n-butanol
Kind, preferably dimethyl sulfoxide.
Further, the fragrant boric acid, elemental selenium, the molar ratio of epoxyethane derivative are 1:(1~5): (1~5), it is excellent
Select 1:3:3.
Further, the temperature of reaction is 100~140 DEG C;The time of reaction is 2-30h.
The utility model has the advantages that the preparation method of beta-hydroxy phenyl selenide compound provided by the invention has the following beneficial effects:
A) reaction efficiently, high income, post-processing it is simple, easy to operate;
B) silver salt is cheap and easy to get;
C) reaction carries out at a lower temperature, mild condition;
D) reaction used catalyst copper chloride is cheap, economical;
E) reaction substrate functional group tolerance is high, substrate spectrum is wide and is easy preparation;
F) reaction efficiency is higher after reaction amplification.
The present invention is using fragrant boronic acid compounds and elemental selenium cheap and easy to get and epoxyethane derivative as reaction raw materials, honest and clean
Under valence copper catalyst and silver salt collective effect, the beta-hydroxy phenyl selenide compound replaced is reacted, operation is simple, instead
Mild condition is answered, large-scale industrial production is suitble to.
Specific embodiment:
In order to illustrate more clearly of the present invention, below with reference to preferred embodiment, the present invention is described further.Ability
Field technique personnel should be appreciated that following specifically described content is illustrative and be not restrictive, this should not be limited with this
The protection scope of invention.
The present invention provides a kind of preparation methods of beta-hydroxy phenyl selenide compound, with virtue boric acid, list as shown in formula (I)
Matter selenium and the epoxyethane derivative as shown in formula (II) are raw material, under the collective effect of copper catalyst, silver salt and alkali, anti-
The intercalation reaction in solvent by elemental selenium is answered to obtain the beta-hydroxy phenyl selenide compound as shown in formula (III);
Above-mentioned reaction process can be indicated with following reaction equations:
Wherein:
(1) fragrant boric acid
Fragrant boric acid has the structure as shown in formula (I),
In formula (I), R be selected from H, phenyl ring, naphthalene nucleus, heterocycle, substituted benzene ring, straight chained alkyl, branched alkyl, halogen, nitro or
Cyano.
Heterocycle is preferably 2,3,4 substitution-pyridines, 1 substitution-isoquinolin, 2 substitution-thiazoles, 2 substitution-miaows
Azoles, 1- aryl-pyrrolidine, 2,3 substitution-indoles, 2,3 substitution-furans, 2,3 substitution-thiophene, 2- replace -1,3 to dislike
Azoles, 2,3 substitution-quinoline.
The preferred 2- methyl of substituted benzene ring, bromine, chlorine, fluorine, trifluoromethyl, nitro, formoxyl, acetyl group, carboxyl, sulfonic acid chloride,
Tert-butyl, methoxyl group, phenyl, hydroxyl, amino, nafoxidine.3- methyl, bromine, chlorine, fluorine, trifluoromethyl, nitro, formoxyl, second
Acyl group, carboxyl, sulfonic acid chloride, tert-butyl, methoxyl group, phenyl, hydroxyl, amino, nafoxidine.4- methyl, bromine, chlorine, fluorine, fluoroform
Base, nitro, formoxyl, acetyl group, carboxyl, sulfonic acid chloride, tert-butyl, methoxyl group, phenyl, hydroxyl, amino, nafoxidine.Straight chain
The preferred methyl of alkyl, ethyl, the preferred tert-butyl of n-hexyl branched alkyl.
(2) copper catalyst
Copper catalyst includes Inorganic Copper or organocopper compound.Inorganic copper catalyst includes copper halide, cuprous halide, copper oxygen
Compound, elemental copper, copper inorganic salts.Organic copper catalyst include acetylacetone copper, copper acetate, cuprous acetate, three fluosulfonic acid copper,
Cuprous sulfocyanide, preferably copper chloride.
Inorganic copper catalyst includes copper oxide (CuO), cuprous iodide (CuI), cuprous bromide (CuBr), stannous chloride
(CuCl), copper powder (Cu), copper fluoride (CuF2), cuprous sulfate (CuSO4), copper chloride (CuCl2), cuprous oxide (Cu2O), preferably
Copper chloride (CuCl2);Organic copper catalyst includes three fluosulfonic acid copper (Cu (OTf)2), acetylacetone copper (Cu (acac)2), acetic acid
Copper (Cu (OAc)2), cuprous sulfocyanide (CuSCN), cuprous acetate (CuOAc).
With mole for measurement unit, the dosage of catalyst is the raw material virtue boric acid compound dosage as shown in formula (I)
1-10%.
(3) silver salt
Silver salt in the present invention be silver oxide, silver nitrate, silver carbonate, silver acetate, silver sulfate, silver tetrafluoroborate, silver bromide,
At least one of silver hexafluoroantimonate, silver trifluoromethanesulfonate, preferably silver nitrate.
With molar amount, the amount ratio of the dosage of the silver salt and the fragrant boric acid is 1:(0.5~2).
(4) alkali
Alkali in the present invention is potassium tert-butoxide, the tert-butyl alcohol is received, potassium carbonate, sodium carbonate, sodium ethoxide, sodium methoxide, potassium fluoride, fluorine
Change caesium, potassium hydroxide, sodium hydroxide, sodium hydride, sodium phosphate, potassium phosphate, sodium acetate, cesium carbonate, ammonium sulfate, in Potassiumiodate extremely
Few one kind, preferably potassium tert-butoxide;With molar amount, the amount ratio of the dosage of the alkali and the fragrant boric acid is 1:(0.5~2).
(5) reaction dissolvent
Solvent used in present invention reaction is organic solvent.Organic solvent can be alcohol, ether, amide, chloralkane, virtue
Fragrant hydrocarbon, dimethyl sulfoxide, ester, heterocyclic arene, aliphatic hydrocarbon.
The present invention can be the polymer of monohydric alcohol, monohydric alcohol as the alcohol of solvent.Alcohol of the invention can be C1-C4's
The alkylol of linear chain or branched chain.The example of alcohol includes but is not limited to methanol, ethyl alcohol, normal propyl alcohol, isopropanol, n-butanol, poly- second two
Alcohol.
The present invention can be simple ether, compound ether, cyclic ethers, preferably cyclic ethers as the ether of solvent.The example of ether includes but not
It is limited to ether, 1,4- dioxane, tetrahydrofuran (THF).
The present invention has N,N-dimethylformamide (DMF) as the example of the amide of solvent.
The present invention includes but is not limited to methylene chloride, chloroform, carbon tetrachloride, 1,2- as the example of the chloralkane of solvent
Dichloroethanes.
The present invention includes but is not limited to benzene,toluene,xylene as the example of the aromatic hydrocarbon of solvent.
The example of organic solvent of the invention further includes dimethyl sulfoxide (DMSO), ethyl acetate, pyridine, n-hexane, excellent
Select dimethyl sulfoxide (DMSO).
(6) reaction temperature
In preparation method of the invention, reaction temperature be 100-140 DEG C, may be, for example, in non-limiting manner 100 DEG C, 110 DEG C,
120 DEG C or 140 DEG C.
(7) reaction time
In the preparation process in accordance with the present invention, the reaction time, there is no particular limitation, such as can pass through liquid chromatographic detection mesh
Product or raw material residual percentage and determine suitable reaction time, it typically is 2-30 hours, in non-limiting manner for example
It is 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 26 hours, 28 hours or 30 hours.
(8) it isolates and purifies
Mixture resulting after reaction can be isolated and purified further, to obtain purer final products.This
The field method well-known to the ordinarily skilled artisan isolated and purified, for example, can using extraction, column chromatography, distillation, decantation, filtering, from
The heart, washing, evaporation, stripping and absorption or its at least two the methods of combination are isolated and purified, such as extraction, column layer
Analysis.
Certainly, it directly reacts if necessary to which the reaction mixture of acquisition can also be introduced directly into other processes to produce
Other products.Optionally, before being introduced into other processes, can to reaction mixing pre-process, such as concentration, extraction and
One of vacuum distillation is a variety of, to obtain crude product or pure product, is then introduced into other processes.
In a preferred embodiment, post-processing step after reaction can be following method: after reaction,
Reaction mixture is cooling, ethyl acetate is then added and is diluted dilution, the solution after dilution is transferred in separatory funnel,
It is extracted with saturated salt solution, isolates water phase and organic phase, then water phase is extracted with ethyl acetate 2-4 times, merged all organic
Phase (i.e. the multiple organic phase of the organic phase of saturated salt solution extraction and separation and ethyl acetate extraction and separation), it is dry with anhydrous sodium sulfate
It is dry, it is concentrated under reduced pressure, silicagel column on concentrated residues object (wherein silica gel is 300-400 mesh silica gel) is mixed with petroleum ether and ether
Solvent is eluent, collects eluent, obtains target product after concentration.
Embodiment 1
The synthesis of 2- phenylseleno cyclohexanol
At room temperature, by fragrant boric acid (0.4mmol), selenium (1.2mmol, 3equiv), copper chloride (0.04mmol), silver nitrate
(0.2mmol, 0.5equiv), reaction dissolvent 2mL DMSO are added in reaction tube, stir 12h under 120 DEG C of reaction temperatures;So
Afterwards by potassium tert-butoxide (0.8mmol, 2equiv), epoxyethane derivative (1.2mmol, 3equiv) is added in reaction tube, 120
It is stirred for 12h under DEG C reaction temperature, is terminated by thin-layer chromatography monitoring reaction, obtains 2- phenylseleno cyclohexanol after reaction.
20mL water and 10mL ethyl acetate extracting operation are added, anhydrous sodium sulfate drying is then added, after five minutes mistake
Filter, filter cake washs (5mL x 3 times) with ethyl acetate, then spins off solvent, obtained after column chromatography for separation product (eluant, eluent:
Petroleum ether: ethyl acetate=6:1), product is yellow liquid, yield 94%;
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows:
1H NMR(500MHZ,CDCl3): δ 7.50 (d, J=7.0Hz, 2H), 7.34-7.27 (m, 3H), 3.33 (s, 1H),
2.92-2.87(m,2H),2.19-2.12(m,2H),1.74-1.61(m,2H),1.43-1.19(m,4H);
The data of the carbon-13 nmr spectra of products therefrom are as follows:
13C NMR(500MHz,CDCl3)δ136.1,129.0,128.1,126.7,72.3,53.6,33.9,33.4,
26.9,24.5。
Embodiment 2
The synthesis of 2- (4- methoxybenzene seleno) cyclohexanol
At room temperature, by 4- methyl virtue boric acid (0.4mmol), selenium (2mmol, 5equiv), copper chloride (0.004mmol),
Silver nitrate (0.8mmol, 2equiv), reaction dissolvent 2mLDMSO are added in reaction tube, are stirred under 100 DEG C of reaction temperatures
15h;Then by potassium tert-butoxide (0.2mmol, 0.5equiv), epoxyethane derivative (2mmol, 5equiv) is added to reaction tube
In, it is stirred for 15h under 100 DEG C of reaction temperatures, is terminated by thin-layer chromatography monitoring reaction, obtains 2- (4- methoxybenzene seleno)
Cyclohexanol.
20mL water and 10mL ethyl acetate extracting operation are added, anhydrous sodium sulfate drying is then added, after five minutes mistake
Filter, filter cake washs (5mL x 3 times) with ethyl acetate, then spins off solvent, obtained after column chromatography for separation product (eluant, eluent:
Petroleum ether: ethyl acetate=6:1), product is yellow liquid, yield 52%;
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows:
1H NMR(500MHz,CDCl3) δ 7.47 (d, J=8.0Hz, 2H), 7.09 (d, J=8.0Hz, 2H), 3.32-3.27
(m,1H),2.97(s,1H),2.85-2.80(m,1H),2.34(s,3H),2.17-2.11(m,2H),1.73-1.70(m,1H),
1.63-1.59(m,1H),1.40-1.18(m,4H);
The data of the carbon-13 nmr spectra of products therefrom are as follows:
13C NMR(500MHz,CDCl3)δ138.3,136.5,129.8,122.6,72.2,58.5,33.9,33.3,
26.9,24.5,21.2。
Embodiment 3
The synthesis of 2- (4- methoxybenzene seleno) cyclohexanol
At room temperature, by 4- methoxyl group virtue boric acid (0.4mmol), selenium (0.4mmol, 1equiv), copper chloride
(0.02mmol), silver nitrate (0.4mmol, 1equiv), reaction dissolvent 2mL DMSO are added in reaction tube, are reacted at 140 DEG C
At a temperature of stir 1h;Then by potassium tert-butoxide (0.4mmol, 1equiv), epoxyethane derivative (0.4mmol, 1equiv) adds
Into reaction tube, it is stirred for 1h under 140 DEG C of reaction temperatures, is terminated by thin-layer chromatography monitoring reaction, obtains 2- (4- methoxyl group
Phenylseleno) cyclohexanol.
20mL water and 10mL ethyl acetate extracting operation are added, anhydrous sodium sulfate drying is then added, after five minutes mistake
Filter, filter cake washs (5mL x 3 times) with ethyl acetate, then spins off solvent, obtained after column chromatography for separation product (eluant, eluent:
Petroleum ether: ethyl acetate=6:1), product is yellow liquid, yield 45%;
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows:
1H NMR(500MHz,CDCl3) δ 7.50 (d, J=9.0Hz, 2H), 6.82 (d, J=8.5Hz, 2H), 3.81 (s,
3H),3.27-3.23(m,1H),2.98(s,1H),2.79-2.73(m,1H),2.13-2.10(m,2H),1.72-1.59(m,
2H),1.33-1.19(m,4H);
The data of the carbon-13 nmr spectra of products therefrom are as follows:
13CNMR(500MHz,CDCl3)δ159.9,138.4,115.9,114.7,71.9,55.3,53.4,33.8,33.2,
26.9,24.5。
Embodiment 4
The synthesis of 2- (4- fluorobenzene seleno) cyclohexanol
At room temperature, by 4- fluorine virtue boric acid (0.4mmol), selenium (1.2mmol, 3equiv), copper chloride (0.4mmol), nitre
Sour silver (0.2mmol, 0.5equiv), reaction dissolvent 2mLDMSO are added in reaction tube, stir under 100 DEG C of reaction temperatures
15h;Then by potassium tert-butoxide (0.8mmol, 2equiv), epoxyethane derivative (1.2mmol, 3equiv) is added to reaction tube
In, it is stirred for 15h under 100 DEG C of reaction temperatures, is terminated by thin-layer chromatography monitoring reaction, obtains 2- (4- fluorobenzene seleno) hexamethylene
Alcohol.
20mL water and 10mL ethyl acetate extracting operation are added, anhydrous sodium sulfate drying is then added, after five minutes mistake
Filter, filter cake washs (5mL x 3 times) with ethyl acetate, then spins off solvent, obtained after column chromatography for separation product (eluant, eluent:
Petroleum ether: ethyl acetate=6:1), product is yellow liquid, yield 96%;
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows:
1H NMR(500MHz,CDCl3) δ 7.57 (t, J=6.5Hz, 2H), 6.99 (t, J=8.5Hz, 2H), 3.29 (s,
1H),2.87-2.81(m,2H),2.17-2.12(m,2H),1.75-1.72(m,1H),1.63-1.62(m,1H),1.38-1.19
(m,4H);
The data of the carbon-13 nmr spectra of products therefrom are as follows:
13C NMR(500MHz,CDCl3)δ163.1(d,JF=247.5Hz), 138.5 (d, JF=8.8Hz), 120.9,
116.3(d,JF=21.3Hz), 72.1,53.7,33.9,33.3,26.8,24.5.
Embodiment 5
The synthesis of 2- (4- carboxylic acid formicester phenylseleno) cyclohexanol
At room temperature, by 4- methoxycarbonyl group virtue boric acid (0.4mmol), selenium (1.2mmol, 3equiv), copper chloride
(0.04mmol), silver nitrate (0.2mmol, 0.5equiv), reaction dissolvent 2mL DMSO are added in reaction tube, anti-at 120 DEG C
12h is stirred at a temperature of answering;Then by potassium tert-butoxide (0.8mmol, 2equiv), epoxyethane derivative (1.2mmol, 3equiv)
It is added in reaction tube, is stirred for 12h under 120 DEG C of reaction temperatures, terminated by thin-layer chromatography monitoring reaction, obtain 2- (4- carboxylic
Sour formicester phenylseleno) cyclohexanol.
20mL water and 10mL ethyl acetate extracting operation are added, anhydrous sodium sulfate drying is then added, after five minutes mistake
Filter, filter cake washs (5mL x 3 times) with ethyl acetate, then spins off solvent, obtained after column chromatography for separation product (eluant, eluent:
Petroleum ether: ethyl acetate=6:1), product is yellow liquid, yield 46%;
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows:
1H NMR(500MHz,CDCl3) δ 7.92 (d, J=8.5Hz, 2H), 7.63 (d, J=8.5Hz, 2H), 3.91 (s,
3H),3.43-3.38(m,1H),3.08-3.03(m,1H),2.75(s,1H),2.22-2.13(m,2H),1.77-1.66(m,
2H),1.49-1.26(m,4H);
The data of the carbon-13 nmr spectra of products therefrom are as follows:
13C NMR(500MHz,CDCl3)δ166.7,134.7,134.3,129.9,129.3,72.8,53.7,52.22,
34.2,33.5,26.8,24.4。
Embodiment 6
The synthesis of 2- (4- formoxyl phenylseleno) cyclohexanol
At room temperature, by 4- aldehyde radical virtue boric acid (0.4mmol), selenium (1.2mmol, 3equiv), copper chloride (0.04mmol),
Silver nitrate (0.2mmol, 0.5equiv), reaction dissolvent 2mLDMSO are added in reaction tube, are stirred under 120 DEG C of reaction temperatures
12h;Then by potassium tert-butoxide (0.8mmol, 2equiv), epoxyethane derivative (1.2mmol, 3equiv) is added to reaction tube
In, it is stirred for 12h under 120 DEG C of reaction temperatures, is terminated by thin-layer chromatography monitoring reaction, obtains 2- (4- formoxyl phenylseleno)
Cyclohexanol.
20mL water and 10mL ethyl acetate extracting operation are added, anhydrous sodium sulfate drying is then added, after five minutes mistake
Filter, filter cake washs (5mL x 3 times) with ethyl acetate, then spins off solvent, obtained after column chromatography for separation product (eluant, eluent:
Petroleum ether: ethyl acetate=6:1), product is yellow liquid, yield 65%;
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows:
1H NMR(500MHz,CDCl3)δ9.97(s,1H),7.77-7.70(m,4H),3.47-3.44(m,1H),3.17-
3.11(m,1H),2.68(s,1H),2.25-2.15(m,2H),1.79-1.67(m,2H),1.57-1.27(m,4H);
The data of the carbon-13 nmr spectra of products therefrom are as follows:
13C NMR(500MHz,CDCl3)δ191.6,137.9,135.2,133.9,129.9,73.1,53.7,34.3,
33.6,26.8,24.4。
Embodiment 7
The synthesis of 2- (1- naphthalene) cyclohexanol
At room temperature, by 1- naphthalene virtue boric acid (0.4mmol), selenium (1.2mmol, 3equiv), copper chloride (0.04mmol), nitre
Sour silver (0.2mmol, 0.5equiv), reaction dissolvent 2mL DMSO are added in reaction tube, stir under 120 DEG C of reaction temperatures
12h;Then by potassium tert-butoxide (0.8mmol, 2equiv), epoxyethane derivative (1.2mmol, 3equiv) is added to reaction tube
In, it is stirred for 12h under 120 DEG C of reaction temperatures, is terminated by thin-layer chromatography monitoring reaction, obtains 2- (1- naphthalene) cyclohexanol.
20mL water and 10mL ethyl acetate extracting operation are added, anhydrous sodium sulfate drying is then added, after five minutes mistake
Filter, filter cake washs (5mL x 3 times) with ethyl acetate, then spins off solvent, obtained after column chromatography for separation product (eluant, eluent:
Petroleum ether: ethyl acetate=6:1), product is yellow liquid, yield 67%;
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows:
1H NMR(400MHz,CDCl3) δ 8.50 (d, J=8.50Hz, 1H), 7.90 (d, J=7.10Hz, 1H), 7.89-
7.91 (m, 2H), 7.56 (t, J=8.0Hz, 1H), 7.50 (t, J=8.0Hz, 1H), 7.37 (t, J=7.50Hz, 1H), 3.46-
3.41 (m, 1H), 3.05-3.00 (m, 1H), 2.89 (s, 1H), 2.12 (t, J=14.33Hz, 2H), 1.68-1.53 (m, 2H),
1.41-1.22(m,4H).
The data of the carbon-13 nmr spectra of products therefrom are as follows:
13C NMR(100MHz,CDCl3)δ136.0,135.7,134.1,129.5,128.6,128.4,127.0,126.9,
126.3,125.7,72.9,53.8,34.2,33.5,26.7,24.3。
Embodiment 8
The synthesis of 2- methyl-1-phenylseleno-2- propyl alcohol
At room temperature, by fragrant boric acid (0.4mmol), selenium (1.2mmol, 3equiv), copper chloride (0.04mmol), silver nitrate
(0.2mmol, 0.5equiv), reaction dissolvent 2mL DMSO are added in reaction tube, stir 12h under 120 DEG C of reaction temperatures;So
Afterwards by potassium tert-butoxide (0.8mmol, 2equiv), methyloxetane (1.2mmol, 3equiv) is added in reaction tube, at 120 DEG C
It is stirred for 12h under reaction temperature, is terminated by thin-layer chromatography monitoring reaction, obtains 2- methyl-1-phenylseleno-2- propyl alcohol.
20mL water and 10mL ethyl acetate extracting operation are added, anhydrous sodium sulfate drying is then added, after five minutes mistake
Filter, filter cake washs (5mL x 3 times) with ethyl acetate, then spins off solvent, obtained after column chromatography for separation product (eluant, eluent:
Petroleum ether: ethyl acetate=6:1), product is yellow liquid, yield 65%.
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows:
1H NMR(400MHz,CDCl3)δ7.56-7.54(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(100MHz,CDCl3)δ132.5,130.9,129.2,127.0,70.4,44.4,29.0。
Embodiment 9
The synthesis of -3 butanol of 4- phenylseleno -1- alkene
At room temperature, by fragrant boric acid (0.4mmol), selenium (1.2mmol, 3equiv), copper chloride (0.04mmol), silver nitrate
(0.2mmol, 0.5equiv), reaction dissolvent 2mL DMSO are added in reaction tube, stir 12h under 120 DEG C of reaction temperatures;So
Afterwards by potassium tert-butoxide (0.8mmol, 2equiv), -1 butylene of 3,4 epoxy (1.2mmol, 3equiv) is added in reaction tube, 120
It is stirred for 12h under DEG C reaction temperature, is terminated by thin-layer chromatography monitoring reaction, obtains -3 butanol of 4- phenylseleno -1- alkene.
20mL water and 10mL ethyl acetate extracting operation are added, anhydrous sodium sulfate drying is then added, after five minutes mistake
Filter, filter cake washs (5mL x 3 times) with ethyl acetate, then spins off solvent, obtained after column chromatography for separation product (eluant, eluent:
Petroleum ether: ethyl acetate=6:1), product is yellow liquid, yield 56%;
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows:
1H NMR(400MHz,CDCl3)δ7.55-7.53(m,2H),7.27-7.25(m,3H),5.91-5.83(m,1H),
5.29 (d, J=17.0Hz, 1H), 5.15 (d, J=10.5Hz, 1H), 4.24-4.19 (m, 1H), 3.13 (dd, J1=4.5Hz, J2
=12.5Hz, 1H), 2.95 (dd, J1=8.0Hz, J2=12.5Hz, 1H), 2.46 (d, J=4Hz, 1H)
The data of the carbon-13 nmr spectra of products therefrom are as follows:
13C NMR(100MHz,CDCl3)δ138.9,133.2,129.3,129.2,127.4,116.0,70.9,36.4。
Embodiment 10
The synthesis of 1- phenoxy group -3- phenylseleno -2- propyl alcohol
At room temperature, by fragrant boric acid (0.4mmol), selenium (1.2mmol, 3equiv), copper chloride (0.04mmol), silver nitrate
(0.2mmol, 0.5equiv), reaction dissolvent 2mL DMSO are added in reaction tube, stir 12h under 120 DEG C of reaction temperatures;So
Afterwards by potassium tert-butoxide (0.8mmol, 2equiv), phenyl glycidyl ether (1.2mmol, 3equiv) is added in reaction tube, 120
It is stirred for 12h under DEG C reaction temperature, is terminated by thin-layer chromatography monitoring reaction, obtains 1- phenoxy group -3- phenylseleno -2- propyl alcohol.
20mL water and 10mL ethyl acetate extracting operation are added, anhydrous sodium sulfate drying is then added, after five minutes mistake
Filter, filter cake washs (5mL x 3 times) with ethyl acetate, then spins off solvent, obtained after column chromatography for separation product (eluant, eluent:
Petroleum ether: ethyl acetate=6:1), product is yellow liquid, yield 84%;
The data of the nuclear magnetic resonance spectroscopy of products therefrom are as follows:
1H NMR(360MHz,CDCl3) δ 7.55-7.53 (m, 2H), 7.27-7.23 (m, 5H), 7.0 (t, J=7.0Hz,
1H), 6.85 (d, J=4.0Hz, 2H), 4.13-4.09 (m, 1H), 4.04-3.98 (m, 2H), 3.21 (dd, J=5.5Hz,
12.5Hz, 1H), 3.13 (dd, J=7.0Hz, 12.5Hz, 1H), 2.76 (d, J=4.0Hz, 1H)
The data of the carbon-13 nmr spectra of products therefrom are as follows:
13C NMR(90MHz,CDCl3)δ158.4,132.9,129.5,129.3,127.4,121.3,114.6,70.5,
69.1,31.9.
It can be seen that by above-described embodiment 1-10, when using preparation method of the invention, can be obtained with high yield, high-purity
To beta-hydroxy phenyl selenide compound.
Embodiment 11-25
In addition to catalyst copper chloride therein is replaced with following copper catalyst respectively, with with highest products collection efficiency
The identical mode of embodiment 1 and implement embodiment 11-25 respectively, the yield of used copper compound and corresponding product is as follows
Shown in table 1.
Table 1
Number | Copper catalyst | Reaction yield (%) |
Embodiment 11 | CuI | 80 |
Embodiment 12 | CuBr | 73 |
Embodiment 13 | Cu2O | 46 |
Embodiment 14 | Cu(OTf)2 | 31 |
Embodiment 15 | Cu(acac)2 | 22 |
Embodiment 16 | CuCl | 84 |
Embodiment 17 | Copper powder | 10 |
Embodiment 18 | CuSCN | 40 |
Embodiment 19 | CuF2 | 90 |
Embodiment 20 | CuCl2 | 94 |
Embodiment 21 | CuSO4 | 56 |
Embodiment 22 | CuOAc | 65 |
Embodiment 23 | CuBr2 | 49 |
Embodiment 24 | CuO | 38 |
Embodiment 25 | Cu(OAc)2 | 35 |
It can be seen that by upper table 1, when using other copper compounds, products collection efficiency is greatly lowered.Thus this is demonstrated
Catalyst copper chloride used in inventing has efficient catalytic performance for the reaction.
Embodiment 26-34
In addition to silver nitrate therein is replaced with following silver salt respectively, with the embodiment 2 with highest products collection efficiency
Identical mode and implement embodiment 26-34 respectively, the yield of used silver salt and corresponding product is as shown in table 2 below.
Table 2
Number | Oxidant | Reaction yield (%) |
Embodiment 26 | Silver oxide | 33 |
Embodiment 27 | Silver nitrate | 94 |
Embodiment 28 | Silver tetrafluoroborate | 89 |
Embodiment 29 | Silver carbonate | 31 |
Embodiment 30 | Silver hexafluoroantimonate | 86 |
Embodiment 31 | Silver acetate | 43 |
Embodiment 32 | Silver trifluoromethanesulfonate | 45 |
Embodiment 33 | Silver bromide | 20 |
Embodiment 34 | Silver sulfate | 21 |
It can be seen that by upper table 2, when using other silver salt, products collection efficiency is greatly lowered.Thus it proves
Silver nitrate used in the present invention is to the reaction system maximally efficient.
Embodiment 35-48
In addition to alkali potassium tert-butoxide therein is replaced with following alkali respectively, with the embodiment with highest products collection efficiency
3 identical modes and implement embodiment 34-44 respectively, the yield of used alkali and corresponding product is as shown in table 3 below.
Table 3
Number | Alkali | Reaction yield (%) |
Embodiment 35 | Potassium carbonate | 84 |
Embodiment 36 | Sodium acetate | 74 |
Embodiment 37 | Sodium methoxide | 88 |
Embodiment 38 | Sodium carbonate | 33 |
Embodiment 39 | Sodium tert-butoxide | 92 |
Embodiment 40 | Sodium hydroxide | 90 |
Embodiment 41 | Potassium phosphate | 82 |
Embodiment 42 | Sodium ethoxide | 22 |
Embodiment 43 | Cesium fluoride | 36 |
Embodiment 44 | Sodium hydride | 45 |
Embodiment 45 | Sodium phosphate | 46 |
Embodiment 46 | Cesium carbonate | 35 |
Embodiment 47 | Ammonium sulfate | 48 |
Embodiment 48 | Potassiumiodate | 38 |
It can be seen that by upper table 3, when using other alkali, in addition under the conditions of highly basic such as sodium tert-butoxide, other alkali yields are still
There is significant decrease;And yield generally reduces under the conditions of middle highly basic and weak base.This demonstrate that the strong and weak suitable selection of alkali is to anti-
Product yield has significantly, even conclusive influence.
Embodiment 49-68
In addition to organic solvent DMSO therein is replaced with following organic solvent respectively, with with highest products collection efficiency
The identical mode of embodiment 4 and implement embodiment 49-68 respectively, the yield of used organic solvent and corresponding product is as follows
Shown in table 4.
Table 4
It can be seen that by upper table 4, when using other organic solvents, in addition in intensive polar solvent such as n,N-Dimethylformamide
It can react, but yield still has significant decrease;And yield is lower under low pole even nonpolar solvent conditions.
In conclusion can clearly be found out by above-mentioned all embodiments, copper is selected from when using using method of the invention
Object is closed as catalyst (especially copper chloride), silver salt (especially silver nitrate), suitable organic solvent (especially DMSO) institute
When the recombination reaction system of composition, it can make simple fragrant boric acid, elemental selenium and epoxyethane derivative that elemental selenium insertion occur anti-
It answers and synthesizes to obtain beta-hydroxy phenyl selenide compound with high yield and high-purity, mentioned for the efficient quick synthesis of such compound
Completely new synthetic route is supplied.
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
Pipe present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that: its according to
So be possible to modify the technical solutions described in the foregoing embodiments, or to some or all of the technical features into
Row equivalent replacement;And these are modified or replaceed, various embodiments of the present invention technology that it does not separate the essence of the corresponding technical solution
The range of scheme.
Claims (15)
1. a kind of preparation method of beta-hydroxy phenyl selenide compound, which is characterized in that with the virtue with the structure as shown in formula (I)
Boric acid, elemental selenium and the epoxyethane derivative as shown in formula (II) are raw material, in the collective effect of copper catalyst, silver salt and alkali
Under, the intercalation reaction in reaction dissolvent through elemental selenium obtains the beta-hydroxy phenyl selenide compound as shown in formula (III);
In formula (I), formula (II) and formula (III), R1、R2It is each independently selected from H, phenyl ring, naphthalene nucleus, heterocycle, substituted benzene ring, straight chain
One of alkyl, branched alkyl, halogen, nitro and cyano.
2. a kind of preparation method of beta-hydroxy phenyl selenide compound according to claim 1, which is characterized in that the copper
Catalyst is organic copper or Inorganic Copper;With molar amount, the dosage of the copper catalyst is the 1-10% of the fragrant boric acid dosage.
3. a kind of preparation method of beta-hydroxy phenyl selenide compound according to claim 2, which is characterized in that the nothing
Machine copper is at least one of Cu oxide, elemental copper, the inorganic salts of copper;
The organic copper is at least one of acetylacetone copper, copper acetate, cuprous acetate, three fluosulfonic acid copper, cuprous sulfocyanide.
4. a kind of preparation method of beta-hydroxy phenyl selenide compound according to claim 3, which is characterized in that the nothing
Machine copper is copper chloride.
5. a kind of preparation method of beta-hydroxy phenyl selenide compound according to claim 1, which is characterized in that the copper
Catalyst is CuO, CuI, CuBr, CuCl, Cu (OTf)2、Cu(acac)2、Cu(OAc)2, copper powder, CuSCN, CuF2、CuSO4、
CuOAc、CuCl2、Cu2At least one of O;With molar amount, the dosage of the copper catalyst is the 1- of the fragrant boric acid dosage
10%.
6. a kind of preparation method of beta-hydroxy phenyl selenide compound according to claim 5, which is characterized in that the copper
Catalyst is CuCl2。
7. a kind of preparation method of beta-hydroxy phenyl selenide compound according to any one of claims 1 to 6, feature exist
In, the silver salt be silver oxide, silver nitrate, silver carbonate, silver acetate, silver sulfate, silver tetrafluoroborate, silver bromide, silver hexafluoroantimonate,
At least one of silver trifluoromethanesulfonate;With molar amount, the amount ratio of the dosage of the silver salt and the fragrant boric acid is 1:
(0.5~2).
8. a kind of preparation method of beta-hydroxy phenyl selenide compound according to claim 7, which is characterized in that the silver
Salt is silver nitrate.
9. a kind of preparation method of beta-hydroxy phenyl selenide compound according to any one of claims 1 to 6, feature exist
In, alkali be potassium tert-butoxide, sodium tert-butoxide, potassium carbonate, sodium carbonate, sodium ethoxide, sodium methoxide, potassium fluoride, cesium fluoride, potassium hydroxide,
At least one of sodium hydroxide, sodium hydride, sodium phosphate, potassium phosphate, sodium acetate, cesium carbonate, ammonium sulfate, Potassiumiodate;With mole
The amount ratio of meter, the dosage of the alkali and the fragrant boric acid is 1:(0.5~2).
10. a kind of preparation method of beta-hydroxy phenyl selenide compound according to claim 9, which is characterized in that alkali is
Potassium tert-butoxide.
11. a kind of preparation method of beta-hydroxy phenyl selenide compound according to any one of claims 1 to 6, feature
It is, the reaction dissolvent is organic solvent, and the organic solvent is dimethyl sulfoxide, n,N-Dimethylformamide, ethyl alcohol, gathers
Ethylene glycol, methylene chloride, ethyl acetate, pyridine, n-hexane, 1,4- dioxane, 1,2- dichloroethanes, toluene, tetrahydrofuran,
At least one of methanol, ether, carbon tetrachloride, dimethylbenzene, benzene, chloroform, normal propyl alcohol, isopropanol, n-butanol.
12. a kind of preparation method of beta-hydroxy phenyl selenide compound according to claim 11, which is characterized in that described
Reaction dissolvent is dimethyl sulfoxide.
13. a kind of preparation method of beta-hydroxy phenyl selenide compound according to any one of claims 1 to 6, feature
It is, fragrant boric acid, elemental selenium, the molar ratio of epoxyethane derivative are 1:(1~5): (1~5).
14. a kind of preparation method of beta-hydroxy phenyl selenide compound according to claim 13, which is characterized in that fragrant boron
Acid, elemental selenium, the molar ratio of epoxyethane derivative are 1:3:3.
15. a kind of preparation method of beta-hydroxy phenyl selenide compound according to any one of claims 1 to 6, feature
It is, the temperature of the reaction is 100~140 DEG C;The time of the reaction is 2-30h.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710711250.XA CN107382803B (en) | 2017-08-18 | 2017-08-18 | A kind of preparation method of beta-hydroxy phenyl selenide compound |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710711250.XA CN107382803B (en) | 2017-08-18 | 2017-08-18 | A kind of preparation method of beta-hydroxy phenyl selenide compound |
Publications (2)
Publication Number | Publication Date |
---|---|
CN107382803A CN107382803A (en) | 2017-11-24 |
CN107382803B true CN107382803B (en) | 2019-03-29 |
Family
ID=60352934
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710711250.XA Active CN107382803B (en) | 2017-08-18 | 2017-08-18 | A kind of preparation method of beta-hydroxy phenyl selenide compound |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN107382803B (en) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108178741B (en) * | 2018-01-10 | 2019-10-22 | 温州大学苍南研究院 | β-alkynes seleno alcohols organic compound synthetic method |
CN108047118B (en) * | 2018-01-10 | 2021-01-22 | 温州大学苍南研究院 | Synthetic method of 3-indolseleno alcohol organic compound |
CN108658822B (en) * | 2018-02-19 | 2020-10-13 | 温州医科大学 | Aryl alkyl selenide compound and preparation method thereof |
CN108912026B (en) * | 2018-02-19 | 2020-10-23 | 温州医科大学 | Alkynyl alkyl selenide compound and preparation method thereof |
CN111793013B (en) * | 2020-06-17 | 2021-12-07 | 温州医科大学 | Synthetic method for preparing aryl methyl selenide compound from selenium methyl bunnt salt and arylboronic acid |
CN112062748B (en) * | 2020-09-16 | 2021-07-27 | 温州大学 | Synthesis method of phenoxaseleno/phenothiazine selenium compound |
CN115232047B (en) * | 2022-06-13 | 2023-10-20 | 台州学院 | Preparation method of 3-phenylseleno-1-acetone derivatives |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103724246A (en) * | 2013-12-04 | 2014-04-16 | 温州大学 | Aryl elemental selenium compound synthesis method |
CN103739536A (en) * | 2013-12-04 | 2014-04-23 | 温州大学 | Diaryl diselenide compound synthesis method |
CN104370785A (en) * | 2014-12-03 | 2015-02-25 | 温州大学 | Synthetic method of Beta-hydroxyl selenide compound |
-
2017
- 2017-08-18 CN CN201710711250.XA patent/CN107382803B/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103724246A (en) * | 2013-12-04 | 2014-04-16 | 温州大学 | Aryl elemental selenium compound synthesis method |
CN103739536A (en) * | 2013-12-04 | 2014-04-23 | 温州大学 | Diaryl diselenide compound synthesis method |
CN104370785A (en) * | 2014-12-03 | 2015-02-25 | 温州大学 | Synthetic method of Beta-hydroxyl selenide compound |
Non-Patent Citations (2)
Title |
---|
Copper-Catalyzed Oxirane-Opening Reaction with Aryl Iodides and Se Powder;Lin Min 等;《The Journal of Organic Chemistry》;20160804;第81卷;第7584-7590页 |
Synthesis of b-hydroxy selenides using benzeneselenol and oxiranes under supramolecular catalysis in the presence of b-cyclodextrin in water;R. Sridhar 等;《Tetrahedron Letters》;20051107;第46卷;第8837-8839页 |
Also Published As
Publication number | Publication date |
---|---|
CN107382803A (en) | 2017-11-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107382803B (en) | A kind of preparation method of beta-hydroxy phenyl selenide compound | |
CN108047107B (en) | The preparation method of diphenyl disenenide ether compound | |
CN107915586B (en) | Phenol compound and preparation method thereof | |
DE112011104615B4 (en) | Organoboron compound and method of making same | |
CN102010447B (en) | Preparation method and application of ruthenium and rhodium transition metal complex functional ionic liquid | |
CN109651225A (en) | A kind of 1- methyl -3- amino -4- aromatic thiohydroxy maleimide compound and preparation method | |
CN107200705B (en) | A kind of preparation method of 3- nitro -2- indolone derivatives | |
CN102766088B (en) | Novel process for synchronizing 4,4'-dibromo-2,2'-bipyridyl | |
CN108047118B (en) | Synthetic method of 3-indolseleno alcohol organic compound | |
CN108658805B (en) | Preparation method of asymmetric azobenzene | |
CN101735220B (en) | Crystal form of 6, 7-dihydro-6-mercapto-5H-pyrazolo[1,2-alpha][1,2,4] triazoliumchloride and preparation method thereof | |
CN106117225A (en) | The synthetic method of benzophenanthrene decane epoxide bridging isobutyltrimethylmethane. phenyl porphyrin metal Zn coordination compound | |
CN112979612B (en) | Method for preparing 2-iodo-heterocyclic aromatic ether at room temperature | |
CN110172076B (en) | Quinoline derivative containing exocyclic double bond and preparation method thereof | |
CN105272918B (en) | Halogenation -1- alkyl -3- vinyl -2,4,5- triarylimidazoles and preparation method and purposes | |
CN105228987A (en) | For the preparation of the method for pyridazine compound | |
CN105209435A (en) | Pyridine- or pyrazine-containing compounds | |
CN110003023B (en) | Preparation method of environment-friendly N, N-dimethylformamide dimethyl acetal | |
CN108727167B (en) | Preparation method of anoplophora chinensis gathering pheromone | |
CN106883237B (en) | A kind of double triazole pentacene quinones and preparation method thereof | |
CN107663149A (en) | A kind of preparation method of phenanthrenequione and its derivative | |
CN102260236B (en) | Preparation method of coumarin compounds | |
CN106957235B (en) | A kind of preparation method of tamoxifen | |
CN107089942B (en) | The preparation method of tegafur, gimeracil and oteracil potassium impurity B CB | |
CN105753821A (en) | Preparation method of 2,5-furandicarboxylic acid |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |