CN107188840A - A kind of synthetic method of asymmetric diaryl selenide compound - Google Patents
A kind of synthetic method of asymmetric diaryl selenide compound Download PDFInfo
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Abstract
The present invention relates to a kind of synthetic method of asymmetric diaryl selenide compound, in organic solvent, under Oxygen Condition, using aryl carboxylic acid and diaryldiselenides as reaction raw materials, in collectively promoting under effect for copper catalyst, part and alkali, asymmetric diaryl selenide compound is obtained by oxidative deamination coupling reaction.Methods described aryl carboxylic acid substrate and copper catalyst are cheap and easy to get, substrate spectrum is extensive, reaction condition is simple, product yield and purity are high, new synthetic route and method is opened up for asymmetric diaryl selenide compound, with good application potential and researching value.
Description
Technical field
The invention belongs to organic compound synthesis technical field, more particularly, to a kind of asymmetric diaryl selenide compound
Synthetic method.
Background technology
So far, selenium element has been widely used in the synthesis of medicine, high polymer material, agricultural chemicals, for example, develop many
The individual 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 the Tegafur containing selenium with antitumor activity
Ester type compound, the rhizoma et Radix Baphicacanthis Cusiae compound of polysaccharide that the selenizing inhibited to various tumor cell strains is modified.Even agriculture
Industry field, wide spectrum is present in bactericide and herbicide selenide compound structure again, and be such as used as crops herbicide contains selenium three
Azoles acid amides.It is substantial amounts of scientific investigations showed that, selenium be constitute glutathione peroxidase active component, suppress as free radical
Agent, effectively prevents beta Cell of islet Oxidative demage, promotes sugared part metabolism, reduction blood glucose and glucose in urine, improves the disease of diabetic
Shape, and cysteine, the methionine of needed by human body are also selenium-containing compound.
Just because of so important containing asymmetric diaryl selenide compound, people synthesize to have carried out to it and largely ground
Study carefully, a plurality of synthetic route and method have been explored at present：
, Bhasin et al. (A convenient synthesis of some symmetrical and in 2004
unsymmetrical diarylmethyl sulfur and selenium compounds：X-ray crystal
structure of diphenylmethylseleno-2-propene and bis[p-chlorophenyl(phenyl)
Methyl] diselenide.Journal of Organometallic Chemistry, 2004,689,3327-3334.) report
The nano oxidized copper catalysis alkyl diselenide in road and oxidative coupling reaction of the aryl boric acid under intensive polar solvent dimethyl sulfoxide
Unsymmetrical selenides compound is prepared, but the reaction needs previously prepared alkyl diselenide compound and aryl boric acid, reaction
Formula is as follows：
, Taniguchi et al. (Magnesium-Induced Copper-Catalyzed Synthesis of in 2004
Unsymmetrical Diaryl Chalcogenide Compounds from Aryl Iodide via Cleavage of
The Se-Se or S-S Bond.J.Org.Chem.2004,69,915-920.) report the copper catalysis virtue of magnesium metal induction
Fragrant iodide synthesize asymmetric diaryl selenide compound with the coupling reaction of diaryldiselenides, because the reaction needs metal
Magnesium causes the carbonyl on aromatic ring as additive, and the functional group such as nitro can't stand, and reaction equation is as follows：
, Taniguch et al. (Convenient Synthesis of Unsymmetrical in 2007
Organochalcogenides Using Organoboronic Acids with Dichalcogenides via
Cleavage of the S-S, Se-Se, or Te-Te Bond by a Copper Catalyst.J.Org.Chem.2007,
72,1241-1245) cuprous iodide and 2 are reported, 2 '-bipyridyl concerted catalysis diaryldiselenides are with alkyl borane reagent strong
Polar solvent DMSO obtains asymmetric diaryl selenide compound with the oxidative coupling reaction under the conditions of water mixed solvent, and defect exists
Previously prepared diaryldiselenides and borane reagent are needed in the reaction, synthesis cost are added, reaction equation is as follows：
, Alves et al. (CuO nanoparticles in 2009：an efficient and recyclable
catalyst for cross-coupling reactions of organic diselenides with aryl
Boronic acids.Tetrahedron Letters, 2009,50,6635-6638) report the nano oxidized hydrocarbon of copper catalysis two
Base diselenide prepares unsymmetrical selenides compound with oxidative coupling reaction of the aryl boric acid under intensive polar solvent dimethyl sulfoxide, so
And the reaction needs previously prepared alkyl diselenide compound and aryl boric acid, reaction equation is as follows：
, Nageswar et al. (Lanthanum (III) Oxide as a Recyclable Catalyst in 2009
the Synthesis of Diaryl Sulfides and Diaryl
Selenides.Eur.J.Org.Chem.59022009,5902-5905.) report the aromatic iodide and two that lanthana promotes
The reaction of aryl diselenide under strongly alkaline conditions is prepared for unsymmetrical selenides compound, but the reaction is made using lanthanide series
Obtain environmental pressure heavier, meeting contaminated soil and water source, reaction equation are as follows：
, Rao et al. (Copper Oxide Nanoparticle-Catalyzed Coupling of Diaryl in 2009
Diselenide with Aryl Halides under Ligand-Free Conditions.Org.Lett.2009,11,
951-953.) report nano oxidized copper catalysis diaryldiselenides and synthesize unsymmetrical selenides with the coupling reaction of aromatic halohydrocarbon
Compound, reaction equation is as follows：
, Ranu et al. (Al in 20102O3-Supported Cu-Catalyzed Electrophilic
Substitution by PhSeBr in Organoboranes, Organosilanes, and Organostannanes.A
Protocol for the Synthesis of Unsymmetrical Diaryl and Alkyl Aryl
Selenides.J.Org.Chem.2010,75,4864-4867.) report the copper catalysis organotin reagent of alumina load with
The coupling reaction of benzene selenium bromine electrophilic reagent prepares unsymmetrical selenides compound, but the reaction needs to carry out copper catalyst uniformly
Ground is dispersed in oxidation aluminium surface, and the previously prepared functional group's tolerance inhibited on its phenyl ring of benzene selenium bromine electrophilic reagent is organic
Tin reagent severe toxicity is so that it is difficult to industrialized production, and reaction equation is as follows：
, Alves et al. (Synthesis of diaryl selenides using electrophilic in 2011
selenium species and nucleophilic boron reagents in ionic liquids.Green
Chem., the nucleophilic displacement of fluorine for 2011,13,2931) reporting electrophilic reagent benzeneselenonyl chloride and aryl borane reagent under the conditions of ionic liquid is anti-
Asymmetric diaryl selenide compound should be obtained, but the synthesis of benzeneselenonyl chloride needs are previously prepared, and using environmentally harmful
Chlorine gas, reaction equation is as follows：
, Alves et al. (Silver-Catalyzed Synthesis of Diaryl Selenides by 2011
Reaction of Diaryl Diselenides with Aryl Boronic Acids.J.Org.Chem.2016,81,
11472-11476.) report silver catalysis aryl borane reagent and asymmetric diaryl selenium is synthesized with the coupling reaction of diaryldiselenides
Ether compound, but the previously prepared scope for causing substrate for being limited in that borane reagent of the reaction is narrower, reaction equation is as follows：
, Ranu et al. (Calcium mediated C-F bond substitution in 2013
Fluoroarenes towards C-chalcogen bond formation.Org.Chem.Front., 2017,4,69-
76.) the aromatic nucleophilic substitution reaction for reporting the fluorobenzene derivatives and diaryldiselenides of electron deficient obtains asymmetric diaryl
Selenide compound, the 2 of fluorobenzene substrate, 4 must have strong electron-withdrawing group group such as nitro, and trifluoromethyl, carbonyl functional group causes richness
The fluorobenzene of electronic functional group's substitution can not participate in reaction, and reaction equation is as follows：
, Ranu et al. (Solvent-Controlled Halo-Selective Selenylation of in 2013
Aryl Halides Catalyzed by Cu(II)Supported on Al2O3.A General Protocol for the
Synthesis of Unsymmetrical Organo Mono-and Bis-Selenides J.Org.Chem.2013,78,
Prepared by the coupling reaction of the copper catalysis aromatic halides and diaryldiselenides that 7145-7153.) report alumina load not right
Claim selenide compound, but the reaction defect is that copper catalyst be evenly dispersed in oxidation aluminium surface, course of reaction
The halide salt of generation is to the heavy load of environment, and reaction equation is as follows：
, Ranu et al. (A general and green procedure for the synthesis of in 2013
organochalcogenides by CuFe2O4nanoparticle catalysed coupling of organoboronic
Acids and dichalcogenides in PEG-400.RSC Adv., 2013,3,1] 7-125.) report and utilize nanometer
CuFe2O4Catalyst, in polyethylene glycol 400 solvent, using dimethyl sulfoxide as additive, realizes borane reagent and diphenyl two
The coupling reaction of selenide obtains unsym-metrical selenides compound, but the reaction is confined to the previously prepared of borane reagent, adds
Financial cost, reaction equation is as follows：
, Ranu et al. (Visible Light Photocatalyzed Direct Conversion of in 2014
Aryl-/Heteroarylamines to Selenides at Room Temperature Org.Lett.2014,16,
1814-1817. reports the denitrification reaction conjunction that dyestuff eosin Y are catalyzed aromatic diazo salt and diaryldiselenides under blue light
Into asymmetric diaryl selenide compound, the defect of the reaction can only carry out low dose of reaction, and be reacted under illumination condition
It is uneven so that experimental repeatability is poor, reaction equation is as follows：
As described above with it is visible, although there are the preparation sides of the asymmetric diaryl selenide derivatives of a variety of synthesis in the prior art
Method, but these methods have cumbersome, raw material mostly needs that previously prepared, side reaction is more, condition is violent, functional group tolerates
The shortcomings such as the poor, substrate spectrum of property is narrow.Therefore, for it is easy, be easily handled, raw material that substrate is cheap and easy to get it is not right to prepare
Claim diaryl selenide derivative to be particularly important, be coupled especially with the oxidation depickling of aryl carboxylic acid and diaryldiselenides
Reaction prepares the reaction of asymmetric diaryl selenide compound, does not report so far, still suffers from what is proceeded to study and explore
Necessity, this is also the basis that the present invention is accomplished and power place.
The content of the invention
First technical problem to be solved by this invention be asymmetric diaryl selenide compound preparation process in grasp
The problem of making complicated.
Second technical problem to be solved by this invention be asymmetric diaryl selenide compound preparation process in official
The problem of tolerance is poor can be rolled into a ball.
3rd technical problem to be solved by this invention is that asymmetric diaryl selenide preparation of compounds is adapted to greatly
The problem of technical scale metaplasia is produced.
To solve above technical problem, the present invention provides following technical proposals：
A kind of asymmetric diaryl selenide compound and preparation method, in organic solvent, under Oxygen Condition, with such as
The diaryldiselenides of the aryl carboxylic acid of structure shown in formula (I) and structure shown in formula (II) are reaction raw materials, in copper catalyst, are matched somebody with somebody
Collectively promoting under effect for body and alkali, the asymmetric diaryl of structure shown in formula (III) is obtained by oxidative deamination coupling reaction
Selenide compound；
Above-mentioned course of reaction, can be represented with following reaction equations：
The mol ratio of the aryl carboxylic acid of structure shown in (I) and the diaryldiselenides of structure shown in formula (II) is 1: 1-
1: 5, preferably 1: 2.
(1) aryl carboxylic acid compound
Aryl carboxylic acid compound in the present invention be 2- nitro -4- methoxy benzoic acids, 2- nitrobenzoic acids, 2- nitros -
5- methyl benzoic acids, 4- trifluoromethylbenzoic acids, 6- methyl -2- nitrobenzoic acids, 2- nitro -4- bromobenzoic acids, 2- nitros -3-
Fluobenzoic acid, 2- nitro -5- fluobenzoic acids, 2- nitro -6- fluobenzoic acids, 2,6- difluoro-benzoic acids, 2- benzoyl benzoic acid
And pentafluoro benzoic acid.
(2) diaryldiselenides compound
The Ar in diaryldiselenides compound in the present invention be 3- bromophenyls, 3- trifluoromethyls, 4- chlorphenyls,
4- Trifluoromethoxyphen-ls, 1- naphthyls, 4- bromophenyls.
(3) catalyst
Catalyst in the present invention be to as shown in formula (I) aryl carboxylic acid of structure, structure shown in formula (II) diaryl
The depickling oxidative coupling reaction of diselenide prepares the catalyst of the asymmetric diaryl selenide compound of structure shown in formula (III)；
It is preferred that the catalyst in the present invention is copper catalyst.Copper catalyst includes Inorganic Copper or organocopper compound.Inorganic copper catalyst
Including inorganic copper catalyst include cupric 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).Organic copper catalysis
Agent includes three fluosulfonic acid copper (Cu (OTf)2), acetylacetone copper (Cu (acac)2), copper acetate (Cu (OAc)2), cuprous sulfocyanide
(CuSCN), cuprous acetate (CuOAc), preferably copper acetate (Cu (OAc)2)。
So that mole for measurement unit, the consumption of catalyst is such as the 1-15% of formula (I) compound amount.Preferred catalyst is used
Measure as 15% of the compound consumption as shown in formula (I).
(3) part
Part in the present invention is triphenylphosphine, tricyclohexyl phosphine, tributylphosphine, 1,10- Phens, 2- acetyl basic rings
Double (phosphono) benzene of hexanone, 4,4 '-dimethyl -2,2 '-bipyridyl, terpyridyl, 2,2 '-bipyridyl or 1,2-, preferably 1,10-
Phen.
So that mole for measurement unit, the consumption of part is the 1-15% of the formula (I) compound amount, preferably 15%.
(4) alkali
Alkali in the present invention is lithium carbonate, cesium carbonate, potassium carbonate, sodium carbonate, sodium acetate, lithium acetate, potassium acetate, phosphoric acid
At least one in potassium, sodium phosphate, sodium tert-butoxide, lithium fluoride, potassium fluoride, sodium fluoride, ammonium carbonate, tert-butyl alcohol lithium or potassium tert-butoxide
Plant, preferably potassium carbonate.
So that mole for measurement unit, the amount ratio of the consumption of the potassium carbonate and the formula (I) compound is 5: 1-1: 1,
Preferably 3: 1.
(5) reaction dissolvent
The solvent used in present invention reaction is organic solvent.Organic solvent can be alcohol, ether, acid amides, chloralkane, virtue
At least one of fragrant hydrocarbon, dimethyl sulfoxide (DMSO), ester, heterocyclic arene, aliphatic hydrocarbon.
The present invention is used as the polymer that the alcohol of solvent can be monohydric alcohol, monohydric alcohol.The alcohol of the present invention can be C1-C4
The alkylol of straight or branched.The example of alcohol includes but is not limited to methanol, ethanol, normal propyl alcohol, isopropanol, n-butanol and 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 is included but not
It is limited to ether, Isosorbide-5-Nitrae-dioxane and tetrahydrofuran (THF).
The present invention has N, N- dimethylformamides as the example of the acid amides of solvent.
The present invention includes but is not limited to dichloromethane, chloroform, carbon tetrachloride and 1 as the example of the chloralkane of solvent,
2- dichloroethanes.
The present invention includes but is not limited to benzene, toluene and dimethylbenzene as the example of the aromatic hydrocarbon of solvent.
The example of the organic solvent of the present invention also includes dimethyl sulfoxide (DMSO) (DMSO), ethyl acetate, pyridine, n-hexane, instead
Answer the preferred toluene of solvent.
(6) reaction temperature
The present invention preparation method in, reaction temperature be 80-150 DEG C, in non-limiting manner for example can for 80 DEG C, 90 DEG C, 100
DEG C, 110 DEG C, 120 DEG C, 130 DEG C, 140 DEG C or 150 DEG C.
(7) reaction time
In the preparation process in accordance with the present invention, there is no particular limitation the reaction time, for example, can be detected by liquid chromatograph
The residual percentage of target product or raw material and determine the suitable reaction time, it typically is 15-30 hours, it is non-limiting for example
For 15 hours, 17 hours, 19 hours, 21 hours, 23 hours, 25 hours, 27 hours, 28 hours or 30 hours.
(8) isolate and purify
The mixture of gained after reaction can further be isolated and purified, purer final products have been obtained.This
The field method well-known to the ordinarily skilled artisan isolated and purified, for example can using extraction, column chromatography, distillation, filtering, centrifuge, wash
Wash, be fractionated and adsorb or at least two method such as combination is isolated and purified, such as extraction, column chromatography.
The reactant mixture of acquisition can also be introduced directly into the directly reaction of other processes if desired certainly to produce
Other products.Optionally, before other processes are incorporated into, reactant mixture can be pre-processed, for example, concentration, extraction
Take with one or more experimental implementations in vacuum distillation, to obtain crude product or pure product, be then incorporated into other processes.
In a preferred embodiment, the post-processing step after reaction terminates can be following method：After reaction terminates,
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 asymmetric diaryl selenide compound as made from above-mentioned preparation method.
The preparation method for the asymmetric diaryl selenide compound that the present invention is provided has the advantages that：
A) react efficiently, high income, post-process it is simple, easy to operate；
B) aryl carboxylic acid and copper catalyst are cheap and easy to get；
C) it is arylseleno reagent using diaryldiselenides；
D) reaction substrate is cheap and easy to get, functional group's tolerance is high；
E) reaction efficiency is higher after reaction amplification.
The present invention is with the aryl carboxylic acid of the structure cheap and easy to get as shown in (I) and the selenium of diaryl two of structure shown in formula (II)
Ether is reaction raw materials, under oxygen reaction atmosphere, in collectively promoting under effect for transition metal copper catalyst, part and alkali, instead
The asymmetric diaryl selenide compound of structure shown in formula (III) should be obtained.Reaction condition, post-processing operation are simple, are adapted to big
Technical scale metaplasia is produced.
Embodiment
Below by specific embodiment, the present invention is described in detail, but the purposes of these exemplary embodiments and
Purpose only be used for enumerate the present invention, not to the present invention real protection scope constitute it is any type of it is any limit, it is more non-will
Protection scope of the present invention is confined to this.
The data and purity of noval chemical compound given by following examples are identified by nuclear magnetic resonance.
Embodiment 1
The synthesis of (4- methoxyl group -2- nitrobenzophenones) (phenyl) selenide
At room temperature, by 2- nitro -4- methoxy benzoic acids (0.4mmol, 1equiv), diphenyl disenenide ether
(0.8mmol, 2equiv), Cu (OAc)2(0.06mmol), 1,10- Phens (0.06mmol), potassium carbonate (1.2mmol,
3equiv) it is added to 2mL toluene in reaction tube, is then charged with oxygen, and is replaced three times, under oxygen reaction environment, 150
24h is stirred under DEG C reaction temperature.After being terminated by thin-layer chromatography monitoring reaction, reactant mixture is cooled down, acetic acid is then added
Ethyl ester is filtered, and then spins off solvent, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether: ether=98: 2), product is Huang
Color liquid, yield 95%, products weight is 117mg.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.80 (d, J=2.8Hz, 1H), 7.69-7.67 (m, 2H), 7.50-7.47 (m,
1H), 7.45-7.42 (m, 2H), 6.93 (dd, J=9.0,2.8Hz, 1H) .6.86 (d, J=9.0Hz, 1H), 3.83 (s, 3H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 157.9,146.1,137.3,131.1,130.0,129.7,128.5,
126.1,122.2,109.3,55.9；
The theoretical calculation and experimental result that high resolution mass spectrum analysis is carried out to product are as follows：
HRMS(TIC)：calcd for C13H11NO3Se[M+H]+309.9977；
Found 309.9976.
Embodiment 2
The synthesis of (5- methyl -2- nitrobenzophenones) phenyl selenide
At room temperature, by 5- methyl 2- nitrobenzoic acids (0.4mmol, 1equiv), diphenyl disenenide ether (0.8mmol,
2equiv), Cu (OAc)2(0.06mmol), 1,10- Phens (0.06mmol), potassium carbonate (1.2mmol, 3equiv) and
2mL toluene is added in reaction tube, is then charged with oxygen, and is replaced three times, under oxygen reaction environment, 150 DEG C of reaction temperature
The lower stirring 24h of degree.After being terminated by thin-layer chromatography monitoring reaction, reactant mixture is cooled down, ethyl acetate filtering is then added,
Then solvent is spun off, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether: ether=98: 2), product is yellow liquid, receive
Rate 90%, products weight is 105mg.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.20 (d, J=8.4Hz, 1H), 7.71-7.69 (m, 2H), 7.51 (t, J=
7.2Hz, 1H), 7.46 (t, J=7.6Hz, 2H), 7.05 (d, J=8.4Hz, 1H), 6.74 (s, 1H), 2.19 (s, 3H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 145.0,143.6,137.4,135.8,130.3,130.0,129.8,
128.2,126.8,126.0,21.6；
The theoretical calculation and experimental result that high resolution mass spectrum analysis is carried out to product are as follows：
HRMS(TIC)：calcd for C13H11NO2Se[M+H]+294.0028
Found 294.0027.
Embodiment 3
The synthesis of (trifluoromethyl of 2- nitros -4) diphenyl selenide
At room temperature, by 2- nitro -4- trifluoromethylbenzoic acids (0.4mmol, 1equiv), diphenyl disenenide ether
(0.8mmol, 2equiv), Cu (OAc)2(0.06mmol), 1,10- Phens (0.06mmol), potassium carbonate (1.2mmol,
3equiv) it is added to 2mL toluene in reaction tube, is then charged with oxygen, and is replaced three times, under oxygen reaction environment, 150
24h is stirred under DEG C reaction temperature.After being terminated by thin-layer chromatography monitoring reaction, reactant mixture is cooled down, acetic acid is then added
Ethyl ester is filtered, and then spins off solvent, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether: ether=98: 2), product is Huang
Color liquid, yield 85%, products weight is 118mg.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.56 (s, 1H), 7.71-7.69 (m, 2H), 7.57-7.54 (m, 1H), 7.51-
7.48 (m, 3H), 7.13 (d, J=8.5Hz, 1H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 145.2,141.3,137.3,131.2,130.4,129.4 (d, JF=
3.3Hz), 128.4 (q, JF=34.4Hz), 127.4,126.9,123.0 (d, JF=272.2Hz), 123.2 (q, JF=
4.1Hz)；
The data of the Enantiomeric excess of products therefrom are as follows：
19F NMR (470MHz, CDCl3)：δ -62.8 (s, 3F)；
The theoretical calculation and experimental result that high resolution mass spectrum analysis is carried out to product are as follows：
HRMS(TIC)：calcd for C13H8F3NO2Se[M+H]+347.9745；
Found 347.9744.
Embodiment 4
The synthesis of (2- methyl -6- nitrobenzophenones) phenyl selenide
At room temperature, by 2- methyl -6- nitrobenzoic acids (0.4mmol, 1equiv), diphenyl disenenide ether (0.8mmol,
2equiv), Cu (OAc)2(0.06mmol), 1,10- Phens (0.06mmol), potassium carbonate (1.2mmol, 3equiv) and
2mL toluene is added in reaction tube, is then charged with oxygen, and is replaced three times, under oxygen reaction environment, 150 DEG C of reaction temperature
The lower stirring 24h of degree.After being terminated by thin-layer chromatography monitoring reaction, reactant mixture is cooled down, ethyl acetate filtering is then added,
Then solvent is spun off, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether: ether=98: 2), product is yellow liquid, receive
Rate 82%, products weight is 96mg.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.60-7.58 (m, 1H), 7.42-7.36 (m, 2H), 7.26-7.20 (m, 4H),
2.34 (s, 3H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 145.2,133.7,131.3,129.4,129.1,127.2,124.2,
121.1,23.9；
The theoretical calculation and experimental result that high resolution mass spectrum analysis is carried out to product are as follows：
HRMS(TIC)：calcd for C13H11NO2Se[M+H]+294.0028；
Found 294.0027.
Embodiment 5
The synthesis of (the bromo- 2- nitrobenzophenones of 4-) phenyl selenide
At room temperature, by the bromo- 2- nitrobenzoic acids (0.4mmol, 1equiv) of 4-, diphenyl disenenide ether (0.8mmol,
2equiv), Cu (OAc)2(0.06mmol), 1,10- Phens (0.06mmol), potassium carbonate (1.2mmol, 3equiv) and
2mL toluene is added in reaction tube, is then charged with oxygen, and is replaced three times, under oxygen reaction environment, 150 DEG C of reaction temperature
The lower stirring 24h of degree.After being terminated by thin-layer chromatography monitoring reaction, reactant mixture is cooled down, ethyl acetate filtering is then added,
Then solvent is spun off, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether: ether=98: 2), product is yellow liquid, receive
Rate 83%, products weight is 118mg.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.45 (d, J=2.1Hz, 1H), 7.70-7.68 (m, 2H), 7.54-7.51 (m,
1H), 7.47 (t, J=7.6Hz, 2H), 7.39 (dd, J=8.7,2.1Hz, 1H), 6.84 (d, J=8.7Hz, 1H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 145.9,137.4,136.5,135.1,131.6,130.2,130.1,
128.7,127.7,118.8；
The theoretical calculation and experimental result that high resolution mass spectrum analysis is carried out to product are as follows：
HRMS(TIC)：calcd for C12H8BrNO2Se[M+H]+357.8977；
Found 357.8978.
Embodiment 6
The synthesis of (the chloro- 2- nitrobenzophenones of 3-) phenyl selenide
At room temperature, by the chloro- 2- nitrobenzoic acids (0.4mmol, 1equiv) of 3-, diphenyl disenenide ether (0.8mmol,
2equiv), Cu (OAc)2(0.06mmol), 1,10- Phens (0.06mmol), potassium carbonate (1.2mmol, 3equiv) and
2mL toluene is added in reaction tube, is then charged with oxygen, and is replaced three times, under oxygen reaction environment, 150 DEG C of reaction temperature
The lower stirring 24h of degree.After being terminated by thin-layer chromatography monitoring reaction, reactant mixture is cooled down, ethyl acetate filtering is then added,
Then solvent is spun off, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether: ether=98: 2), product is yellow liquid, receive
Rate 80%, products weight is 100mg.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.61-7.59 (m, 2H), 7.43-7.40 (m, 1H), 7.38-7.33 (m, 3H),
7.18 (t, J=8.0Hz, 1H), 7.14 (dd, J=8.0,1.2Hz, 1H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 135.6,131.7,131.2,129.9,129.4,129.3,129.0,
128.2,126.5；
The theoretical calculation and experimental result that high resolution mass spectrum analysis is carried out to product are as follows：
HRMS(TIC)：calcd for C12H8ClNO2Se[M+H]+313.9482；
Found 313.9484.
Embodiment 7
The synthesis of (the fluoro- 2- nitrobenzophenones of 5-) phenyl selenide
At room temperature, by the fluoro- 2- nitrobenzoic acids (0.4mmol, 1equiv) of 5-, diphenyl disenenide ether (0.8mmol,
2equiv), Cu (OAc)2(0.06mmol), 1,10- Phens (0.06mmol), potassium carbonate (1.2mmol, 3equiv) and
2mL toluene is added in reaction tube, is then charged with oxygen, and is replaced three times, under oxygen reaction environment, 150 DEG C of reaction temperature
The lower stirring 24h of degree.After being terminated by thin-layer chromatography monitoring reaction, reactant mixture is cooled down, ethyl acetate filtering is then added,
Then solvent is spun off, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether: ether=98: 2), product is yellow liquid, receive
Rate 69%, products weight is 82mg.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.37 (dd, J=9.1,5.1Hz, 1H), 7.71 (m, 2H), 7.56-7.53 (m,
1H), 7.51-7.48 (m, 2H), 6.97-6.93 (m, 1H), 6.62 (dd, J=9.4,2.7Hz, 1H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 164.3 (d, JF=257.6Hz), 141.8,139.9 (d, JF=8.7Hz),
137.4,130.4,128.7 (d, JF=10.4Hz), 127.7,116.6 (d, JF=26.9Hz), 113.3 (d, JF=22.4Hz)；
The data of the Enantiomeric excess of products therefrom are as follows：
19F NMR (470MHz, CDCl3)：δ -102.6 (s, 1F)；
The theoretical calculation and experimental result that high resolution mass spectrum analysis is carried out to product are as follows：
HRMS(TIC)：calcd for C12H8FNO2Se[M+H]+297.9777；
Found 297.9775.
Embodiment 8
The synthesis of phenyl (2- phenylselenos phenyl) ketone
At room temperature, by 2- benzoyls benzoic acid (0.4mmol, 1equiv), diphenyl disenenide ether (0.8mmol,
2equiv), Cu (OAc)2(0.06mmol), 1,10- Phens (0.06mmol), potassium carbonate (1.2mmol, 3equiv) and
2mL toluene is added in reaction tube, is then charged with oxygen, and is replaced three times, under oxygen reaction environment, 150 DEG C of reaction temperature
The lower stirring 24h of degree.After being terminated by thin-layer chromatography monitoring reaction, reactant mixture is cooled down, ethyl acetate filtering is then added,
Then solvent is spun off, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether: ether=98: 2), product is yellow liquid, receive
Rate 56%, products weight is 76mg.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.80 (d, J=7.4Hz, 2H), 7.64 (d, J=6.6Hz, 2H), 7.58-
7.57 (m, 2H), 7.49-7.46 (m, 2H), 7.39-7.34 (m, 3H), 7.27-7.19 (m, 3H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 196.6,137.7,137.5,137.0,136.1,132.6,131.8,
131.6,131.5,130.1,129.5,128.5,128.3,125.0；
The theoretical calculation and experimental result that high resolution mass spectrum analysis is carried out to product are as follows：
HRMS(TIC)：calcd for C19H14OSe[M+H]+339.0283；
Found 339.0284.
Embodiment 9
The synthesis of (2,6- difluorophenyl) phenyl selenide
At room temperature, by 2,6- difluoro-benzoic acids (0.4mmol, 1equiv), diphenyl disenenide ether (0.8mmol,
2equiv), Cu (OAc)2(0.06mmol), 1,10- Phens (0.06mmol), potassium carbonate (1.2mmol, 3equiv) and
2mL toluene is added in reaction tube, is then charged with oxygen, and is replaced three times, under oxygen reaction environment, 150 DEG C of reaction temperature
The lower stirring 24h of degree.After being terminated by thin-layer chromatography monitoring reaction, reactant mixture is cooled down, ethyl acetate filtering is then added,
Then solvent is spun off, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether: ether=98: 2), product is yellow liquid, receive
Rate 77%, products weight is 83mg.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.44-7.42 (m, 2H), 7.36-7.30 (m, 1H), 7.23-7.22 (m, 3H),
6.96-6.93 (m, 2H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 163.2 (d, JF=247.1Hz), 163.1 (d, JF=247.1Hz), 131.9,
131.5,131.3 (t, JF=10.0Hz), 130.0,129.2,127.3111.6 (q, JF=5.3Hz), 105.8 (t, JF=
26.2Hz)；
The data of the Enantiomeric excess of products therefrom are as follows：
19F NMR (470MHz, CDCl3)：δ -98.5 (s, 2F)；
The theoretical calculation and experimental result that high resolution mass spectrum analysis is carried out to product are as follows：
HRMS(TIC)：calcd for C12H8F2Se[M+H]+270.9832；
Found 270.9833.
Embodiment 10
The synthesis of (pentafluorophenyl group) (phenyl) selenide
At room temperature, by pentafluoro benzoic acid (0.4mmol, 1equiv), diphenyl disenenide ether (0.8mmol, 2equiv), Cu
(OAc)2(0.06mmol), 1,10- Phens (0.06mmol), potassium carbonate (1.2mmol, 3equiv) and 2mL toluene are added
Into reaction tube, oxygen is then charged with, and is replaced three times, under oxygen reaction environment, 24h is stirred under 150 DEG C of reaction temperatures.
After being terminated by thin-layer chromatography monitoring reaction, reactant mixture is cooled down, ethyl acetate filtering is then added, then spins off molten
Agent, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether: ether=98: 2), product is yellow liquid, yield 90%, production
Thing weight is 117mg.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.53-7.52 (m, 2H), 7.32-7.25 (m, 3H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 196.6,137.7,137.5,137.0,136.1,132.6,131.8,
131.6,131.5,130.1,129.5,128.5,128.3,125.0；
The data of the Enantiomeric excess of products therefrom are as follows：
19F NMR (470MHz, CDCl3)：δ -126.0 (d, JF=26.5Hz, 2F), -151.5 (t, JF=21.3Hz,
1F), -160.0-160.1 (m, 2F)；
The theoretical calculation and experimental result that high resolution mass spectrum analysis is carried out to product are as follows：
HRMS(TIC)：calcd for C19H14OSe[M+H]+324.9550；
Found 324.9551.
Embodiment 11
The synthesis of (4- methoxyl group -2- nitrobenzophenones) (3- trifluoromethyls) selenide
At room temperature, by 2- nitro -4- methoxy benzoic acids (0.4mmol, 1equiv), two (3- trifluoromethyls) two
Selenide (0.8mmol, 2equiv), Cu (OAc)2(0.06mmol), 1,10- Phens (0.06mmol), potassium carbonate
(1.2mmol, 3equiv) and 2mL toluene are added in reaction tube, are then charged with oxygen, and are replaced three times, in oxygen reaction
Under environment, 24h is stirred under 150 DEG C of reaction temperatures.After being terminated by thin-layer chromatography monitoring reaction, reactant mixture is cooled down, so
Ethyl acetate filtering is added afterwards, then spins off solvent, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether: ether=98:
2), product is yellow liquid, and yield 78%, products weight is 117mg.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.97 (s, 1H), 7.88 (d, J=7.6Hz, 1H), 7.83 (d, J=2.7Hz,
1H), 7.74 (d, J=7.9Hz, 1H), 7.57 (t, J=7.7Hz, 1H), 6.98 (dd, J=9.0,2.8Hz, 1H), 6.82 (d, J
=7.9Hz, 1H), 3.86 (s, 3H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 158.3,140.4,133.7,133.6,132.2,130.9,130.3,
129.8,126.4,124.5,122.4,109.5,55.9；
The data of the Enantiomeric excess of products therefrom are as follows：
19F NMR (470MHz, CDCl3)：δ -62.7 (s, 3F)；
The theoretical calculation and experimental result that high resolution mass spectrum analysis is carried out to product are as follows：
HRMS(TIC)：calcd for C14H10F3NO3Se[M+H]+377.9851；
Found 377.9852.
Embodiment 12
The synthesis of (4- chlorphenyls) (4- methoxyl group -2- nitrobenzophenones) selenide
At room temperature, by 2- nitro -4- methoxy benzoic acids (0.4mmol, 1equiv), two (4- chlorphenyls) diselenides
(0.8mmol, 2equiv), Cu (OAc)2(0.06mmol), 1,10- Phens (0.06mmol), potassium carbonate (1.2mmol,
3equiv) it is added to 2mL toluene in reaction tube, is then charged with oxygen, and is replaced three times, under oxygen reaction environment, 150
24h is stirred under DEG C reaction temperature.After being terminated by thin-layer chromatography monitoring reaction, reactant mixture is cooled down, acetic acid is then added
Ethyl ester is filtered, and then spins off solvent, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether: ether=98: 2), product is Huang
Color liquid, yield 61%, products weight is 84mg.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.82 (d, J=2.7Hz, 1H), 7.62-7.61 (m, 2H), 7.42-7.40 (m,
2H), 6.96 (dd, J=9.0,2.9Hz, 1H), 6.84 (d, J=9.0Hz, 1H), 3.85 (s, 3H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 158.1,146.2,138.6,136.3,130.9,130.3,126.7,
125.4,122.3,109.3,55.9；
The theoretical calculation and experimental result that high resolution mass spectrum analysis is carried out to product are as follows：
HRMS(TIC)：calcd for C13H10ClNO3Se[M+H]+343.9587；
Found 343.9588.
Embodiment 13
The synthesis of (4- methoxyl group -2- nitrobenzophenones) (1- naphthyls) selenide
At room temperature, by 2- nitro -4- methoxy benzoic acids (0.4mmol, 1equiv), two (1- naphthyls) diselenides
(0.8mmol, 2equiv), Cu (OAc)2(0.06mmol), 1,10- Phens (0.06mmol), potassium carbonate (1.2mmol,
3equiv) it is added to 2mL toluene in reaction tube, is then charged with oxygen, and is replaced three times, under oxygen reaction environment, 150
24h is stirred under DEG C reaction temperature.After being terminated by thin-layer chromatography monitoring reaction, reactant mixture is cooled down, acetic acid is then added
Ethyl ester is filtered, and then spins off solvent, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether: ether=98: 2), product is Huang
Color liquid, yield 75%, products weight is 144mg.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.23 (d, J=8.4Hz, 1H), 8.05 (dd, J=6.9Hz, 1H), 8.01 (d,
J=8.2Hz, 1H), 7.90 (d, J=8.1Hz, 1H), 7.84 (s, 1H), 7.55-7.47 (m, 3H), 6.75-6.73 (m, 1H),
6.57 (d, J=8.9Hz, 1H), 3.79 (s, 3H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 157.9,146.1,137.7,135.2,134.3,131.4,131.0,
128.8,128.1,127.6,127.5,126.3,125.6,122.2,109.4,55.8；
The theoretical calculation and experimental result that high resolution mass spectrum analysis is carried out to product are as follows：
HRMS(TIC)：calcd for C17H13NO3Se[M+H]+360.0134；
Found 360.0133.
Embodiment 14
The synthesis of (4- bromophenyls) (2- nitrobenzophenones) selenide
At room temperature, by 2- nitro -4- methoxy benzoic acids (0.4mmol, 1equiv), two (4- bromophenyls) diselenides
(0.8mmol, 2equiv), Cu (OAc)2(0.06mmol), 1,10- Phens (0.06mmol), potassium carbonate (1.2mmol,
3equiv) it is added to 2mL toluene in reaction tube, is then charged with oxygen, and is replaced three times, under oxygen reaction environment, 150
24h is stirred under DEG C reaction temperature.After being terminated by thin-layer chromatography monitoring reaction, reactant mixture is cooled down, acetic acid is then added
Ethyl ester is filtered, and then spins off solvent, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether: ether=98: 2), product is Huang
Color liquid, yield 93%, products weight is 133mg.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.32 (dd, J=8.1,1.5Hz, 1H), 7.60-7.56 (m, 4H), 7.36-
7.28 (m, 2H), 6.97 (dd, J=8.0,1.3Hz, 1H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 145.6,138.9,135.2,133.8,133.3,130.1,127.1,
126.2,126.0,124.9；
The theoretical calculation and experimental result that high resolution mass spectrum analysis is carried out to product are as follows：
HRMS(TIC)：calcd for C12H8BrNO2Se[M+H]+357.8977；
Found 357.8976.
Embodiment 15
The synthesis of (4- methoxyl group -2- nitrobenzophenones) (4- Trifluoromethoxyphen-ls) selenide
At room temperature, by 2- nitro -4- methoxy benzoic acids (0.4mmol, 1equiv), two (4- Trifluoromethoxyphen-ls)
Diselenide (0.8mmol, 2equiv), Cu (OAc)2(0.06mmol), 1,10- Phens (0.06mmol), potassium carbonate
(1.2mmol, 3equiv) and 2mL toluene are added in reaction tube, are then charged with oxygen, and are replaced three times, in oxygen reaction
Under environment, 24h is stirred under 150 DEG C of reaction temperatures.After being terminated by thin-layer chromatography monitoring reaction, reactant mixture is cooled down, so
Ethyl acetate filtering is added afterwards, then spins off solvent, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether: ether=98:
2), product is yellow liquid, and yield 91%, products weight is 143mg.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.82 (s, 1H), 7.72 (d, J=7.8Hz, 2H), 7.27 (d .J=7.8Hz,
2H), 7.74 (d, J=7.9Hz, 1H), 6.98 (d, J=8.7Hz, 1H), 6.85 (d, J=8.9Hz, 1H), 3.85 (s, 3H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 158.2,150.4,146.3,138.9,132.6,132.1,130.9,
126.8,125.1,122.3,122.2,120.3 (q, JF=257.9), 109.5,55.9；
The data of the Enantiomeric excess of products therefrom are as follows：
19F NMR (470MHz, CDCl3)：δ -57.7 (s, 3F)；
The theoretical calculation and experimental result that high resolution mass spectrum analysis is carried out to product are as follows：
HRMS(TIC)：calcd for C14H10F3NO3Se[M+H]+377.9851；
Found 377.9852.
Embodiment 16
The synthesis of (3- bromophenyls) (4- methoxyl group -2- nitrobenzophenones) selenide
At room temperature, by 2- nitro -4- methoxy benzoic acids (0.4mmol, 1equiv), two (3- bromophenyls) diselenides
(0.8mmol, 2equiv), Cu (OAc)2(0.06mmol), 1,10- Phens (0.06mmol), potassium carbonate (1.2mmol,
3equiv) it is added to 2mL toluene in reaction tube, is then charged with oxygen, and is replaced three times, under oxygen reaction environment, 150
24h is stirred under DEG C reaction temperature.After being terminated by thin-layer chromatography monitoring reaction, reactant mixture is cooled down, acetic acid is then added
Ethyl ester is filtered, and then spins off solvent, product (eluant, eluent is obtained through column chromatography for separation：Petroleum ether: ether=98: 2), product is Huang
Color liquid, yield 77%, products weight is 119mg.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 7.83 (d, J=2.7Hz, 1H), 7.81-7.80 (m, 1H), 7.77-7.56 (m,
1H), 7.37-7.32 (m, 2H), 6.98 (dd, J=9.0,2.8Hz, 1H), 6.81 (d, J=8.9Hz, 1H), 3.86 (s, 3H)；
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 158.3,146.4,139.1,133.8,131.7,131.6,131.4,
130.9,128.6,124.3,122.4,109.4,55.9；
The theoretical calculation and experimental result that high resolution mass spectrum analysis is carried out to product are as follows：
HRMS(TIC)：calcd for C13H10BrNO3Se[M+H]+387.9082；
Found 387.9080.
It can be seen that, when using the method described in the present invention, can be obtained with high yield, high-purity by above-described embodiment 1-16
To asymmetric diaryl selenide compound.
Embodiment 17-25
In addition to catalyst acetic acid copper therein is replaced with into following copper catalyst respectively, with highest products collection efficiency
The identical mode of implementation 1 and implement embodiment 17-25 respectively, use the yield such as following table of copper compound and corresponding product
Shown in 1.
Table 1
| Numbering | Copper catalyst | Reaction yield (%) |
| Embodiment 17 | Do not react | |
| Embodiment 18 | CuCl2 | 28 |
| Embodiment 19 | CuBr2 | 34 |
| Embodiment 20 | CuI | 29 |
| Embodiment 21 | CuF2 | 46 |
| Embodiment 22 | CuCl | 52 |
| Embodiment 23 | Cu(OTf)2 | 17 |
| Embodiment 24 | Cu(acac)2 | 38 |
| Embodiment 25 | CuO | 54 |
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 acetic acid copper used in invention has efficient catalytic performance to the reaction.
Embodiment 26-33
Except by ligand 1 therein, 10- Phens replace with respectively it is following with external, with being produced with highest product
The identical mode of embodiment 1 of rate and implement embodiment 26-33 respectively, use the yield of copper compound and corresponding product such as
Shown in table 2 below.
Table 2
| Numbering | Part | Reaction yield (%) |
| Embodiment 26 | Triphenylphosphine | Do not react |
| Embodiment 27 | Tricyclohexyl phosphine | Do not react |
| Embodiment 28 | Tributylphosphine | Do not react |
| Embodiment 29 | 2- acetyl cyclohexanones | Do not react |
| Embodiment 30 | 4,4 '-dimethyl -2,2 '-bipyridyl | 36 |
| Embodiment 31 | Terpyridyl | Do not react |
| Embodiment 32 | 2, double (phosphono) benzene of 2 '-bipyridyl or 1,2- | 19 |
| Embodiment 33 | 27 |
It can be seen that by upper table 2, when using other parts, products collection efficiency is very low even without spawn.Thus prove
Ligand 1 used in the present invention, raising of the 10- Phens to the reaction yield is extremely critical.
Embodiment 34-42
In addition to alkali potassium carbonate therein is replaced with into following inorganic base respectively, with the implementation with highest products collection efficiency
The identical mode of example 1 and implement embodiment 34-42 respectively, use the yield such as table 3 below institute of alkali cpd and corresponding product
Show.
Table 3
| Numbering | Alkali | Reaction yield (%) |
| Embodiment 34 | Lithium carbonate | Do not react |
| Embodiment 35 | Sodium carbonate | 17 |
| Embodiment 36 | Cesium carbonate | Do not react |
| Embodiment 37 | Potassium phosphate | Do not react |
| Embodiment 38 | Sodium phosphate | Do not react |
| Embodiment 39 | Tert-butyl alcohol lithium | Do not react |
| Embodiment 40 | Sodium tert-butoxide | Do not react |
| Embodiment 41 | Potassium tert-butoxide | Do not react |
| Embodiment 42 | Sodium acetate | Do not react |
It can be seen that, when using other alkali, almost do not react, it is the reaction thus to demonstrate potassium carbonate by upper table 3
Successful key factor, and it is maximally efficient to the reaction system.
Embodiment 43-53
In addition to organic solvent toluene therein is replaced with into following organic solvent respectively, with highest products collection efficiency
The identical mode of embodiment 1 and implement embodiment 43-53 respectively, use the yield of organic solvent and corresponding product as follows
Shown in table 4.
Table 4
It can be seen that by upper table 4, when using other organic solvents, except in non-polar solven benzene, ortho-xylene and equal three
Toluene can react, but yield still has reduction；And there is no spawn under the conditions of highly polar and weak ligand solvent.This is proved
Can the appropriately selected of organic solvent carry out significant, even conclusive influence to reaction.
In summary, can clearly it be found out by above-mentioned all embodiments, when the method using the present invention is to use copper compound
It is used as catalyst (especially copper acetate), part (1,10- Phen), alkali (especially potassium carbonate), suitable organic solvent
During the recombination reaction system that (especially toluene) is constituted, aryl carboxylic acid and diaryldiselenides can be made to occur oxidation depickling even
Connection reacts and obtains asymmetric diaryl selenide compound with high yield and high-purity synthesis, is the efficient quick of such compound
Synthesis provides brand-new synthetic route.
Finally it should be noted that：Various embodiments above is merely illustrative of the technical solution of the present invention, rather than its limitations；To the greatest extent
The present invention is described in detail with reference to foregoing embodiments for pipe, it will be understood by those within the art that：Its according to
Right scientific research is modified to the technical scheme described in foregoing embodiments, or which part or all technical characteristic are entered
Row equivalent substitution；And these modifications or replacement, the essence of appropriate technical solution is departed from various embodiments of the present invention technology
The scope of scheme.
Claims (10)
1. a kind of synthetic method of asymmetric diaryl selenide compound, it is characterised in that in organic solvent, Oxygen Condition
Under, using the diaryldiselenides with the aryl carboxylic acid of structure as shown in formula (I) and structure shown in formula (II) as reaction raw materials,
Copper catalyst, part and alkali are collectively promoted under effect, and structure shown in formula (III) is obtained not by oxidative deamination coupling reaction
Symmetrical diaryl selenide compound；
In formula (I), (II) and (III), Ar is phenyl or substituted benzene ring；R independently selected from nitro, benzoyl, trifluoromethyl,
Trifluoromethoxy, fluorine, chlorine, bromine, methoxyl group or methyl.
2. preparation method according to claim 1, it is characterised in that the copper catalyst be stannous chloride, cuprous iodide,
Cuprous bromide, cupric oxide, copper chloride, copper bromide, copper fluoride, three fluosulfonic acid copper, acetylacetone copper, copper acetate, copper powder, thiocyanic acid
It is cuprous；With molar amount, the consumption of the copper catalyst is the 1-15% of the formula (I) compound amount.
3. preparation method as claimed in claim 1, it is characterised in that the part is triphenylphosphine, tricyclohexyl phosphine, three fourths
Base phosphine, 1,10- Phens, 2- acetyl cyclohexanones, 4,4 '-dimethyl -2,2 '-bipyridyl, terpyridyl, 2,2 '-connection pyrrole
Pyridine or double (phosphono) benzene of 1,2-；With molar amount, the consumption of the part is the 1-15% of the formula (I) compound amount.
4. preparation method as claimed in claim 1, it is characterised in that the alkali is lithium carbonate, cesium carbonate, potassium carbonate, carbonic acid
Sodium, sodium acetate, lithium acetate, potassium acetate, potassium phosphate, sodium phosphate, sodium tert-butoxide, lithium fluoride, potassium fluoride, sodium fluoride, ammonium carbonate, uncle
Butanol lithium or potassium tert-butoxide；With molar amount, the consumption of the alkali is the 1-300% of the formula (I) compound amount.
5. preparation method as claimed in claim 1, it is characterised in that the reaction dissolvent is organic solvent, described organic molten
Agent be dimethyl sulfoxide (DMSO), DMF, ethanol, polyethylene glycol, dichloromethane, ethyl acetate, pyridine, n-hexane,
The alkane of Isosorbide-5-Nitrae-dioxy six, 1,2- dichloroethanes, toluene, tetrahydrofuran, methanol, ether, carbon tetrachloride, dimethylbenzene, toluene, chloroform,
At least one of normal propyl alcohol, isopropanol, n-butanol or any combination.
6. the preparation method of asymmetric diaryl selenide compound according to claim 1, it is characterised in that (I) institute
The mol ratio for showing the aryl carboxylic acid of structure and the diaryldiselenides of structure shown in formula (II) is 1: 1-1: 5.
7. the preparation method of asymmetric diaryl selenide compound according to claim 1, it is characterised in that the scope
Temperature is 80-150 DEG C.
8. the preparation method of asymmetric diaryl selenide compound according to claim 1, it is characterised in that the reaction
Time is 15-30h.
9. the synthetic method of the asymmetric diaryl selenide compound as described in claim 1 to 9, it is characterised in that described anti-
It should comprise the following steps：Aryl carboxylic acid, diaryldiselenides, copper catalyst, alkali, part and solvent are added in reaction vessel,
Then continuous 3 times of operation is evacuated-be oxygenated to reaction vessel, and 15-30h is reacted in 80-150 DEG C of oil bath, will after reaction terminates
Ethyl acetate filtering is added after reaction solution cooling, is concentrated under reduced pressure, (wherein silica gel is 300- by pillar layer separation by concentrate
400 mesh silica gel), be 98: 2 mixed liquors for eluant, eluent using petroleum ether and ether volume ratio, collect eluent, spin off solvent obtain as
Asymmetric diaryl selenide compound shown in formula (III).
10. a kind of asymmetric diaryl selenide compound, it is characterised in that the asymmetric diaryl selenium of structure shown in formula (III)
Ether compound；
Wherein, Ar is 3- bromophenyls, 3- Trifluoromethoxyphen-ls, 4- chlorphenyls, 4- Trifluoromethoxyphen-ls, 4- bromophenyls.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108456146A (en) * | 2018-02-02 | 2018-08-28 | 浙江工业大学 | A kind of method that drug functional group prepares aromatic ether applied to C-H methoxylations |
| CN110272366A (en) * | 2019-07-30 | 2019-09-24 | 云南大学 | The synthetic method of diaryl selenides |
| CN111620800A (en) * | 2020-06-17 | 2020-09-04 | 温州医科大学 | Method for preparing aryl methyl selenide compound by decarboxylation, selenylation and methylation of aromatic carboxylic acid |
| CN111848480A (en) * | 2019-11-21 | 2020-10-30 | 天津科技大学 | Method for synthesizing aryl difluoromethyl seleno ether from arylboronic acid and application thereof |
| CN111995554A (en) * | 2020-07-24 | 2020-11-27 | 浙江工业大学 | Method for preparing asymmetric organic selenium ether compound by metal-free chemical oxidation method |
| CN112409232A (en) * | 2020-10-23 | 2021-02-26 | 天津科技大学 | Method for synthesizing asymmetric aryl selenide and aryl tellurium ether based on aryl azo sulfone |
| CN113788774A (en) * | 2021-09-10 | 2021-12-14 | 温州医科大学 | Preparation method of 4-seleno-methoxynaphthalene |
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108456146A (en) * | 2018-02-02 | 2018-08-28 | 浙江工业大学 | A kind of method that drug functional group prepares aromatic ether applied to C-H methoxylations |
| CN108456146B (en) * | 2018-02-02 | 2020-12-25 | 浙江工业大学 | Method for preparing aromatic ether by applying drug functional group to C-H methoxylation |
| CN110272366A (en) * | 2019-07-30 | 2019-09-24 | 云南大学 | The synthetic method of diaryl selenides |
| CN110272366B (en) * | 2019-07-30 | 2021-04-02 | 云南大学 | Method for synthesizing diaryl selenide |
| CN111848480A (en) * | 2019-11-21 | 2020-10-30 | 天津科技大学 | Method for synthesizing aryl difluoromethyl seleno ether from arylboronic acid and application thereof |
| CN111620800A (en) * | 2020-06-17 | 2020-09-04 | 温州医科大学 | Method for preparing aryl methyl selenide compound by decarboxylation, selenylation and methylation of aromatic carboxylic acid |
| CN111620800B (en) * | 2020-06-17 | 2021-12-07 | 温州医科大学 | Method for preparing aryl methyl selenide compound by decarboxylation, selenylation and methylation of aromatic carboxylic acid |
| CN111995554A (en) * | 2020-07-24 | 2020-11-27 | 浙江工业大学 | Method for preparing asymmetric organic selenium ether compound by metal-free chemical oxidation method |
| CN111995554B (en) * | 2020-07-24 | 2022-07-22 | 浙江工业大学 | Method for preparing asymmetric organic selenium ether compound by metal-free chemical oxidation method |
| CN112409232A (en) * | 2020-10-23 | 2021-02-26 | 天津科技大学 | Method for synthesizing asymmetric aryl selenide and aryl tellurium ether based on aryl azo sulfone |
| CN112409232B (en) * | 2020-10-23 | 2023-04-07 | 天津科技大学 | Method for synthesizing asymmetric aryl selenide and aryl tellurium ether based on aryl azo sulfone |
| CN113788774A (en) * | 2021-09-10 | 2021-12-14 | 温州医科大学 | Preparation method of 4-seleno-methoxynaphthalene |
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