CN107011251A - One kind 2（2 chlorophenoxies）The preparation method and use of pyridine compounds - Google Patents
One kind 2（2 chlorophenoxies）The preparation method and use of pyridine compounds Download PDFInfo
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- CN107011251A CN107011251A CN201710220499.0A CN201710220499A CN107011251A CN 107011251 A CN107011251 A CN 107011251A CN 201710220499 A CN201710220499 A CN 201710220499A CN 107011251 A CN107011251 A CN 107011251A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
- C07D213/643—2-Phenoxypyridines; Derivatives thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
Abstract
The present invention relates to a kind of preparation method and use of 2 (2 chlorophenoxy) pyridine compounds, in organic solvent, using 2 phenoxypyridines and N chlorosuccinimides as reaction raw materials, in collectively promoting under effect for transition metal palladium catalyst and p-methyl benzenesulfonic acid additive, 2 (2 chlorophenoxy) pyridine compounds are obtained by the chlorination of phenyl ring C H bond activations.Methods described substrate spectrum is extensive, reaction condition gentle, post processing is simple and yield and purity of product are high, is that 2 (2 chlorophenoxy) pyridine compounds have opened up new synthetic route and method, 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 2- (2- chlorophenoxies) pyridine chemical combination
The preparation method and use of thing.
Background technology
O-chlorphenol is widely present in active medicine, the structural elements fragment of agricultural chemical compound, in organic conjunction and medicine
Field plays important role and effect, therefore enjoys organic chemist to pay close attention to.So far, people are multiple specific
Application field is for example medical, drug molecule of the chemical development containing 2- chlorophenoxy structures：Such as a- adrenoreceptor agonists
The Raclopride and antiviral drugs arildone of lofexidine, d2 dopamine receptor positive electron tracer.Even in agriculture field,
Wide spectrum is present in bactericide and herbicide the precursor structure again, for example, having high-efficiency low-toxicity wide-spectrum bactericide P applied levels at present
It is pushed to the market as preventing and treating paddy rice leaf spot and fruit freshness preserving.Meanwhile, woods chlorophenol also serves as important organic conjunction
Into intermediate, it can be used to prepare Anthranilate insecticides.In addition to above-mentioned application, 2- chlorobenzene amphyls
The intermediates such as Anthranilate insecticides Piao Wei medicine intermediate and acid-base indicator chlorophenol red are alternatively arranged as,
And herbicide dicamba intermediate, nitrogen fertilizer potentiating agent, leather fungicide etc..
Just because of such important function of 2- chlorobenzene amphyls, people synthesize to it has carried out numerous studies, and opens
Phenyl ring chloro synthetic method is have issued, mainly including following several chemical synthesis process：
, Calogeropoulou et al. (Simple and Efficient Method for the in 2011
Halogenation of Oxygenated Aromatic Compounds.Synlett, 2011,11,1537-1542) report
Phenol and the concentrated hydrochloric acid of 37% concentration obtain 2- chlorobenzene phenolic compounds under the oxidation of 30% concentration hydrogen peroxide.But should
Reaction needs to use substantial amounts of concentrated hydrochloric acid as substrate so that functional group's tolerance on phenol ring is poor, but also has
4- chlorophenols accessory substance is produced so that target product is difficult to separate, and reaction equation is as follows：
Rogic in 1981 et al. (Sulfuryl Chloride as a Reagent for Selective
Chlorination of Symmetrical Ketones and Phenols.J.Org.Chem.1981,46,4486-
4489.) symmetrical phenol and thionyl chloride are reported in dichloromethane solvent, ether as alkali chlorination.Defect is this
Reaction is limited only to 4-TBP and 4- phenylphenol substrates, and substrate spectrum is narrower, and produces the 2- chlorine for being difficult to separate
Phenol and 4- chlorobenzene phenol mixtures, using thionyl chloride as chlorination reagent, for industrialized production instrument and equipment requirement compared with
Height, corrosivity is strong, pollutes headlight shortcoming, and reaction equation is as follows：
As described above with it is visible, although there is a variety of preparation methods for preparing o-chlorphenol derivative, but this in the prior art
A little methods have the shortcomings such as cumbersome, chlorine is hypertoxic, condition is violent, yield is relatively low, substrate expansion difference mostly.Cause
This, for it is easy, be easily handled, the preparation method of the o-chlorphenol derivative that reaction condition is gentle, and exploitation efficiently, it is cheap
Simple 2- phenoxypyridines c h bond chlorination, do not report so far, still suffer from proceed to study and explore must
Will.Particularly diclofenac sodium development in recent years is very rapid, with increasingly extensive, original of the pairing into diclofenac sodium of application
Material 2,6- chlorophenesic acids demand can also be increased considerably, and be also one of current study hotspot.
The content of the invention
Here, applicant is intended to explanation, the technical scheme is that in state natural sciences fund (numbering：
21602158) it is accomplished, expresses thanks herein under subsidy.
First technical problem to be solved by this invention is in the preparation process of 2- (- chlorophenoxy) pyridine compounds
The problem of complex operation.
Second technical problem to be solved by this invention is to take off pyridine protection in 2- (2- chlorophenoxies) pyridine compounds
The problem of group synthesizes o-chlorphenol derivative.
3rd technical problem to be solved by this invention is the o-chlorphenol preparation process of functionalization is adapted to big rule
The problem of mould industrialized production.To solve above technical problem, the present invention provides following technical proposals：
A kind of preparation method of 2- (2- chlorophenoxies) pyridine compounds, with the 2- benzene oxygen with the structure as shown in formula (I)
Yl pyridines are reaction raw materials with N- chlorosuccinimides, under nitrogen reaction atmosphere, are added in transition metal palladium catalyst and acid
Plus agent is collectively promoted under effect, the chlorination activated in reaction dissolvent by phenyl ring c h bond obtained as shown in formula (II)
2- (2- chlorophenoxies) pyridine compounds；
In formula (I) and (II), R be each independently selected from halogen, alkoxy, straight chained alkyl, branched alkyl, trifluoromethyl,
Trifluoromethylthio, formoxyl, aldehyde radical, aryl or cyano group.
Palladium catalyst is organic palladium or inorganic palladium compound；With molar amount, the consumption of palladium catalyst is the 2- benzene oxygen
The 1-5% of yl pyridines consumption.Inorganic palladium is one kind in palladium bichloride or 10% palladium-carbon catalyst；The organic palladium be palladium,
Tetra-triphenylphosphine palladium, double (tricyclohexyl phosphine) palladiums, palladium diiodide, dibrominated palladium, four (acetonitrile) tetrafluoro boric acid palladiums, three (two benzal
Benzylacetone) two palladiums, tetrachloro-palladium acid sodium, two (cyano group benzene) palladium chlorides, two (acetonitrile) palladium chlorides, two (acetylacetone,2,4-pentanedione) palladiums, three
At least one of fluoroacetic acid palladium and double (triphenylphosphine) palladium chlorides, preferably palladium.Palladium catalyst is PdCl2、Pd
(OAc)2、Pd(PPh3)4、Pd(PCy3)2、PdI2、PdBr2、Pd(CH3CN)4(BF4)2、Na2PdCl4、Pd(C6H5CN)2Cl2、Pd
(CH3CN)2Cl2、Pd(acac)2、Pd(TFA)2With Pd (PPh3)2Cl2At least one of, preferably Pd (OAc)2；With mole
Meter, the consumption of the palladium catalyst is the 1-5% of 2- phenoxypyridines consumptions.
Acid additive is acetic acid, propionic acid, butyric acid, valeric acid, pivalic acid, benzoic acid, 4- nitrobenzoic acids, 2,6- dimethoxys
At least one of benzoic acid, p-methyl benzenesulfonic acid, benzene sulfonic acid, trifluoromethanesulfonic acid and trifluoroacetic acid, preferably p-methyl benzenesulfonic acid,
With molar amount, the consumption of the acid additive and the 1-5% of 2- phenoxypyridines consumptions.
Reaction dissolvent is organic solvent, and the organic solvent is alcohol, ether, acid amides, chloralkane, aromatic hydrocarbon, dimethyl Asia
At least one of sulfone, ester, heterocyclic arene, aliphatic hydrocarbon.
The reaction dissolvent is organic solvent, and the organic solvent is dimethyl sulfoxide (DMSO), DMF, second
Alcohol, polyethylene glycol, dichloromethane, ethyl acetate, pyridine, n-hexane, the alkane of Isosorbide-5-Nitrae-dioxy six, 1,2- dichloroethanes, toluene, tetrahydrochysene
At least one of furans, methanol, ether, carbon tetrachloride, dimethylbenzene, benzene, chloroform, normal propyl alcohol, isopropanol, n-butanol, preferably
Ethyl acetate.
The mol ratio of the 2- phenoxypyridines and N- chlorosuccinimides is 1: 1-1: 5, preferably 1: 1.
The temperature of the scope is 0-40 DEG C；The time of the reaction is 15-30h.
The 2- as made from above-mentioned preparation method (2- chlorophenoxies) pyridine compounds.
The preparation method of 2- (2- chlorophenoxies) pyridine compounds that the present invention is provided has the advantages that：
A) react efficiently, high income, post-process it is simple, easy to operate；
B) acid additive is cheap and easy to get；
C) reaction is carried out in room temperature, mild condition；
D) reaction substrate functional group tolerance is high, substrate spectrum is wide and easily prepares；
E) reaction efficiency is higher after reaction amplification.
2- phenoxypyridines compound and N- chlorosuccinimides of the invention easily to prepare is reaction raw materials, in nitrogen
Under solid/liquid/gas reactions atmosphere, in collectively promoting under effect for transition metal palladium catalyst and acid additive, reaction obtains 2- (2- chlorobenzene oxygen
Base) pyridine compounds.Operation is simple, and reaction condition is gentle, is adapted to large-scale industrial production.
In order to illustrate more clearly of the present invention, 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, and this should not be limited with this
The protection domain of invention.
The present inventor has now surprisingly been found that a kind of method for efficiently building 2- (2- chlorophenoxies) pyridine compounds.
The present invention improves a kind of preparation method of 2- (2- chlorophenoxies) pyridine compounds, with 2- phenoxypyridines chemical combination
Thing is reaction raw materials with N- chlorosuccinimides, under nitrogen reaction atmosphere, in transition metal palladium catalyst and acid additive
Collectively promote under effect, the 2- as shown in formula (II) is obtained by the reaction of the c h bond function dough of phenyl ring in reaction dissolvent
(2- chlorophenoxies) pyridine compounds.
Above-mentioned course of reaction, can be represented with following reaction equations：
(1) 2- phenoxypyridines compound
2- phenoxypyridines compound has the structure as shown in formula (I)：
In formula (I), R is each independently selected from halogen, alkoxy, straight chained alkyl, branched alkyl, trifluoromethyl, fluoroform
Sulfenyl, formoxyl, aldehyde radical, aryl or cyano group.
(2) catalyst
Catalyst in the present invention is to prepare 2- (2- to 2- phenoxypyridines compound and the reaction of N- chlorosuccinimides
Chlorophenoxy) pyridine catalyst.It is preferred that the catalyst in the present invention is palladium catalyst.Palladium catalyst includes inorganic palladium or organic
Palladium compound.Inorganic palladium catalyst includes palladium bichloride and 10% palladium-carbon catalyst.Organic palladium catalyst includes palladium, four triphens
Base phosphine palladium, double (tricyclohexyl phosphine) palladiums, palladium diiodide, dibrominated palladium, four (acetonitrile) tetrafluoro boric acid palladiums, three (dibenzalacetones)
Two palladiums, tetrachloro-palladium acid sodium, two (cyano group benzene) palladium chlorides, two (acetonitrile) palladium chlorides, two (acetylacetone,2,4-pentanedione) palladiums, palladium trifluoroacetate
With double (triphenylphosphine) palladium chlorides, preferably palladium.
So that mole for gauge unit, the consumption of catalyst is the raw material 2- phenoxypyridines class compounds as shown in formula (I)
The 1-5% of consumption.Preferred catalyst consumption is 5% of the raw material 2- phenoxypyridines compound amounts as shown in formula (I).
(3) acid additive
Acid additive includes acetic acid, propionic acid, butyric acid, valeric acid, pivalic acid, benzoic acid, 4- nitrobenzoic acids, 2,6- dimethoxies
Yl benzoic acid, p-methyl benzenesulfonic acid, benzene sulfonic acid, trifluoromethanesulfonic acid and trifluoroacetic acid, preferably p-methyl benzenesulfonic acid.
So that mole for gauge unit, the consumption of acid additive is the raw material 2- phenoxypyridines class chemical combination as shown in formula (I)
The 1-5% of thing consumption.Preferred acid additive amount is 5% of the raw material 2- phenoxypyridines compound amounts as shown in formula (I).
(4) reaction dissolvent
The solvent used in present invention reaction is organic solvent.Organic solvent can be alcohol, ether, acid amides, chloralkane, virtue
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 DMF (DMF) 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, excellent
Select ethyl acetate.
(5) reaction temperature
The present invention preparation method in, reaction temperature be 0-40 DEG C, in non-limiting manner for example can for 0 DEG C, 10 DEG C, 20 DEG C,
30 DEG C or 40 DEG C.
(6) 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, example in non-limiting manner
Such as it is 15 hours, 17 hours, 19 hours, 21 hours, 23 hours, 25 hours, 27 hours, 28 hours or 30 hours.
(7) 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,
Reactant mixture is cooled down, ethyl acetate is then added and is diluted, the solution simple filtration after dilution is concentrated under reduced pressure, will
Silicagel column (wherein silica gel is 300-400 mesh silica gel), using petroleum ether and ether mixed solvent as eluent, receives on concentrated residues thing
Collect eluent, target product is obtained after concentration.
The present invention relates to formula (II) 2- (2- chlorophenoxies) pyridine compounds pyridine technology is taken off using art methods
The purposes of adjacent phenol derivatives of the method synthesis as shown in formula (III).Above-mentioned course of reaction, can use following reaction equation tables
Show：
Wherein R is as defined above.
Enumerated as one kind is exemplary, formula (III) compound can be prepared as follows：The formula of 1 equivalent is added in reaction bulb
(II) compound, the Methyl triflate of 2 equivalents flows back 2 hours in 0.1mol/L toluene solvant, after reaction terminates, subtracts
Pressure concentration boils off toluene solvant, add with formula (II) mole ratio for 2 equivalents metallic sodium in methanol solvate, reacted at 80 DEG C
24 hours, cooling was concentrated under reduced pressure and boils off methanol solvate, and by silicagel column on concentrated residues thing, (wherein silica gel is 300-400 mesh silicon
Glue), using petroleum ether and ethyl acetate mixed solvent as eluent, eluent is collected, the target production such as formula (III) is obtained after concentration
Thing.
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 2- (the chloro- 5- methyl-phenoxvs of 2-) pyridine
At room temperature, by palladium (5mol%), p-methyl benzenesulfonic acid (5mol%), 2- (3- methyl-phenoxvs) pyridine
(0.4mmol, 1equiv), N- chlorosuccinimides (0.4mmol, 1equiv) stir 24h under 40 DEG C of reaction temperatures；Pass through
After thin-layer chromatography monitoring reaction terminates, 20mL ethyl acetate is added, then simple filtration spins off solvent, obtained through chromatographing post separation
To product (eluant, eluent：Petroleum ether: ether=97: 3), product is yellow liquid, and yield 69%, products weight is 69.6mg；
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.08 (d, J=5.0Hz, 1H), 7.62 (t, J=7.0Hz, 1H), 7.26 (d, J
=8.5Hz, 1H), 6.95-6.87 (m, 4H)
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 162.1,148.4,146.5138.4,137.2129.1,125.9,123.1,
117.4,110.0,20.0.
The theoretical calculation and experimental result that elementary analysis is carried out to product are as follows：
Anal.Calcd.For C12H10ClNO：C, 65.61；H, 4.59；N, 6.38；
Found：C, 65.62；H, 4.58；N, 6.37；
Embodiment 2
The synthesis of 2- (the chloro- 4- fluorophenoxies of 2-) pyridine
At room temperature, by palladium (5mol%), p-methyl benzenesulfonic acid (5mol%), 2- (4- fluorophenoxies) pyridine
(0.4mmol, 1equiv), N- chlorosuccinimides (0.4mmol, 1equiv) stir 24h under 40 DEG C of reaction temperatures；Pass through
After thin-layer chromatography monitoring reaction terminates, 20mL ethyl acetate is added, then simple filtration spins off solvent, obtained through chromatographing post separation
To product (eluant, eluent：Petroleum ether: ether=97: 3), product is yellow liquid, and yield 76%, products weight is 102.8mg；
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.18-8.12 (m, 1H), 7.72-7.66 (m, 1H), 7.23-7.17 (m, 1H),
(7.10-6.89 m, 4H)
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 163.3 (d, JF=97.5Hz), 160.4 (d, JF=22.5Hz), 158.5 (d,
JF=26.2Hz), 147.6,139.4,124.7,122.7,118.1 (d, JF=92.5Hz), 116.1,114.7,111.4.
The data of the Enantiomeric excess of products therefrom are as follows：
19F NMR (470MHz, CDCl3)：δ -118.5 (s, 1F)
The theoretical calculation and experimental result that elementary analysis is carried out to product are as follows：
Anal.Calcd.For C11H7ClFNO：C, 59.08；H, 3.16；N, 6.26；
Found：C, 59.09；H, 3.15；N, 6.25；
Embodiment 3
The synthesis of 1- (the chloro- 4- of 3- (2- pyridines epoxide)-phenyl) ethyl ketone
At room temperature, by palladium (5mol%), p-methyl benzenesulfonic acid (5mol%), 1- (4- (2- pyridines epoxide)-phenyl)
Ethyl ketone (0.4mmol, 1equiv), N- chlorosuccinimides (0.8mmol, 1equiv) stir 24h under 40 DEG C of reaction temperatures；
After terminating by thin-layer chromatography monitoring reaction, 20mL ethyl acetate is added, then simple filtration spins off solvent, through chromatographic column point
From obtaining product (eluant, eluent：Petroleum ether: ether=97: 3), product is yellow liquid, yield 51%, and products weight is
50.6mg；
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.08 (s, 2H), 8.00 (d, J=4.5Hz, 1H), 7.72 (t, J=6.0Hz,
1H), (s, the 3H) of 7.30 (s, 2H), 7.09-7.02 (m, 2H), 2.55
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 183.3,172.3,161.6,151.6,147.3,140.0,130.9,
130.3,119.3,110.9,67.5,60.7,29.2.
The theoretical calculation and experimental result that elementary analysis is carried out to product are as follows：
Anal.Calcd.For C13H10ClNO2：C, 63.04；H, 4.07；N, 5.66；
Found：C, 63.03；H, 4.06；N, 5.67；
Embodiment 4
The synthesis of 2- (the chloro- 4- of 2- (methyl sulphur) phenoxy group) pyridine
At room temperature, by palladium (5mol%), p-methyl benzenesulfonic acid (5mol%), 2- (4- (methyl sulphur) phenoxy group) pyridine
(0.4mmol, 1 equiv), N- chlorosuccinimides (0.4mmol, 1equiv) stir 24h under 40 DEG C of reaction temperatures；It is logical
Cross after thin-layer chromatography monitoring reaction terminates, 20mL ethyl acetate is added, then simple filtration spin off solvent, through chromatographing post separation
Obtain product (eluant, eluent：Petroleum ether: ether=97: 3), product is yellow liquid, and yield 22%, products weight is 22.2mg；
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.20 (s, 1H), 7.70 (t, J=8.5Hz, 1H), 7.53 (d, J=8.5Hz,
2H), 7.11-7.02 (m, 3H)
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 153.9,147.7,139.6,132.7,130.2,129.6,121.7,
120.4,118.8,111.8,108.5,29.7.
The theoretical calculation and experimental result that elementary analysis is carried out to product are as follows：
Anal.Calcd.For C12H10ClNOS：C, 57.25；H, 4.00；N, 5.56；
Found：C, 57.25；H, 4.01；N, 5.55；
Embodiment 5
The synthesis of the chloro- 4- of 3- (2- pyridines epoxide) benzaldehyde
At room temperature, by palladium (5mol%), p-methyl benzenesulfonic acid (5mol%), 4- (2- pyridines epoxide) benzaldehyde
(0.4mmol, 1 equiv), N- chlorosuccinimides (0.4mmol, 1equiv) stir 24h under 40 DEG C of reaction temperatures；It is logical
Cross after thin-layer chromatography monitoring reaction terminates, 20mL ethyl acetate is added, then simple filtration spin off solvent, through chromatographing post separation
Obtain product (eluant, eluent：Petroleum ether: ether=97: 3), product is yellow liquid, and yield 46%, products weight is 42.6mg；
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 9.96 (s, 1H), 8.16 (d, J=3.0Hz, 1H), 8.01 (s, 1H), 7.84-
7.76 (m, 2H), 7.36 (d, J=8.5Hz, 1H), 7.09-7.06 (m, 2H)
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 189.8,162.2,154.9,147.1,140.4,133.6,131.4,
129.2,128.3,123.7119.5,111.8.
The theoretical calculation and experimental result that elementary analysis is carried out to product are as follows：
Anal.Calcd.For C12H8ClNO2：C, 61.69；H, 3.45；N, 5.99；
Found：C, 61.70；H, 3.44；N, 5.98；
Embodiment 6
The synthesis of 2- (the chloro- 4- biphenylyloxies of 3-) pyridine
At room temperature, by palladium (5mol%), p-methyl benzenesulfonic acid (5mol%), 2- (4- biphenylyloxies) pyridine
(0.4mmol, 1equiv), N- chlorosuccinimides (0.4mmol, 1equiv) stir 24h under 40 DEG C of reaction temperatures；Pass through
After thin-layer chromatography monitoring reaction terminates, 20mL ethyl acetate is added, then simple filtration spins off solvent, obtained through chromatographing post separation
To product (eluant, eluent：Petroleum ether: ether=97: 3), product is yellow liquid, and yield 81%, products weight is 91.2mg；
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.13 (d, J=6.0Hz, 1H), 7.75 (t, J=8.5Hz, 1H), 7.60-
7.54 (m, 4H), 7.46-7.37 (m, 4H), 7.10-7.01 (m, 2H)
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 172.2,162.1,147.4,145.4,140.0,137.7,138.3,
129.9,129.0,128.2,127.4,127.0,121.5,118.8,110.7.
The theoretical calculation and experimental result that elementary analysis is carried out to product are as follows：
Anal.Calcd.For C17H12ClNO：C, 72.47；H, 4.29；N, 4.97；
Found：C, 72.48；H, 4.30；N, 4.96；
Embodiment 7
The synthesis of the chloro- 4- of 3- (2- pyridines epoxide) benzonitrile
At room temperature, by palladium (5mol%), p-methyl benzenesulfonic acid (5mol%), 4- (2- pyridines epoxide) benzonitrile
(0.4mmol, 1equiv), N- chlorosuccinimides (0.4mmol, 1equiv) stir 24h under 40 DEG C of reaction temperatures；Pass through
After thin-layer chromatography monitoring reaction terminates, 20mL ethyl acetate is added, then simple filtration spins off solvent, obtained through chromatographing post separation
To product (eluant, eluent：Petroleum ether: ether=97: 3), product is yellow liquid, and yield 51%, products weight is 46.6mg；
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.14 (d, J=3.5Hz, 1H), 7.79-7.76 (m, 2H), 7.61-7.59 (m,
1H), 7.32 (d, J=8.5Hz, 1H), 7.09-7.07 (m, 2H),
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 162.0,154.0,147.4,140.0,134.3,131.7,128.3,
124.2,119.6,117.4,111.8,109.6.
The theoretical calculation and experimental result that elementary analysis is carried out to product are as follows：
Anal.Calcd.For C12H7ClN2O：C, 62.49；H, 3.06；N, 12.15；
Found：C, 62.50；H, 3.07；N, 12.14；
Embodiment 8
The synthesis of 2- (chloro- (6- the methoxyl groups)-phenoxy groups of 2-) pyridine
At room temperature, by palladium (5mol%), p-methyl benzenesulfonic acid (5mol%), 2- (2- (methoxyl group) phenoxy group) pyridine
(0.4mmol, 1equiv), N- chlorosuccinimides (0.4mmol, 1equiv) stir 24h under 40 DEG C of reaction temperatures；Pass through
After thin-layer chromatography monitoring reaction terminates, 20mL ethyl acetate is added, then simple filtration spins off solvent, obtained through chromatographing post separation
To product (eluant, eluent：Petroleum ether: ether=97: 3), product is yellow liquid, and yield 63%, products weight is 58.8mg；
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.14 (d, J=5.5Hz, 1H), 7.71-7.66 (m, 1H), 7.31-7.20 (m,
1H), 7.03-6.91 (m, 4H), 3.74 (s, 3H)
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 163.2,150.7,147.4,139.4,129.5,125.6,123.5,
113.7,111.1,110.9.56.2.
The theoretical calculation and experimental result that elementary analysis is carried out to product are as follows：
Anal.Calcd.For C12H10ClNO2：C, 61.16；H, 4.28；N, 5.94；
Found：C, 61.15；H, 4.27；N, 5.95；
Embodiment 9
The synthesis of 2- (the chloro- 6- methylphenoxies of 2-) pyridine
At room temperature, by palladium (5mol%), p-methyl benzenesulfonic acid (5mol%), 2- (2- methyl-phenoxvs) pyridine
(0.4mmol, 1equiv), N- chlorosuccinimides (0.4mmol, 1equiv) stir 24h under 40 DEG C of reaction temperatures；Pass through
After thin-layer chromatography monitoring reaction terminates, 20mL ethyl acetate is added, then simple filtration spins off solvent, obtained through chromatographing post separation
To product (eluant, eluent：Petroleum ether: ether=97: 3), product is yellow liquid, and yield 81%, products weight is 71.0mg；
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.12 (d, J=3.5Hz, 1H), 7.70 (t, J=8.5Hz, 1H), 7.30 (d, J
=7.5Hz, 1H), 7.18-7.08 (m, 2H), 6.98-6.94 (m, 2H)
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 161.5,147.0,146.5,138.5,132.7,128.4,126.9,
126.8,124.9,117.2,109.2,15.8.
The theoretical calculation and experimental result that elementary analysis is carried out to product are as follows：
Anal.Calcd.For C12H10ClNO：C, 65.61；H, 4.59；N, 5.38；
Found：C, 65.60；H, 4.60；N, 5.37；
Embodiment 10
The synthesis of 2- (the bromo- 6- chlorophenoxies of 2-) pyridine
At room temperature, by palladium (5mol%), p-methyl benzenesulfonic acid (5mol%), 2- (2- bromobenzenes epoxide) pyridine
(0.4mmol, 1equiv), N- chlorosuccinimides (0.4mmol, 1equiv) stir 24h under 40 DEG C of reaction temperatures；Pass through
After thin-layer chromatography monitoring reaction terminates, 20mL ethyl acetate is added, then simple filtration spins off solvent, obtained through chromatographing post separation
To product (eluant, eluent：Petroleum ether: ether=97: 3), product is yellow liquid, and yield 71%, products weight is 80.2mg；
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.10 (d, J=4.5Hz, 1H), 7.74 (t, J=7.0Hz, 1H), 7.55 (d, J
=8.5Hz, 1H), 7.43 (d, J=8.0Hz, 1H), 7.09-6.99 (m, 3H)
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 161.9,147.5,147.3,139.6,131.8,129.7,129.5,
126.9,118.9,118.7.110.7.
The theoretical calculation and experimental result that elementary analysis is carried out to product are as follows：
Anal.Calcd.For C11H7BrClNO：C, 46.43；H, 2.48；N, 4.92；
Found：C, 46.44；H, 2.47；N, 4.93；
Embodiment 11
The synthesis of 2- (2- chloro- 6- (trifluoromethyl) phenoxy group) pyridine
At room temperature, by palladium (5mol%), p-methyl benzenesulfonic acid (5mol%), 2- (2- (trifluoromethyl) phenoxy group) pyrrole
Pyridine (0.4mmol, 1equiv), N- chlorosuccinimides (0.4mmol, 1equiv) stir 24h under 40 DEG C of reaction temperatures；It is logical
Cross after thin-layer chromatography monitoring reaction terminates, 20mL ethyl acetate is added, then simple filtration spin off solvent, through chromatographing post separation
Obtain product (eluant, eluent：Petroleum ether: ether=97: 3), product is yellow liquid, and yield 47%, products weight is 51.4mg；
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.08 (s, 1H), 7.74 (t, J=8.5Hz, 1H), 7.67-7.63 (m, 2H),
7.32 (d, J=8.0Hz, 1H), 7.08-6.99 (m, 2H)
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 172.4,162.4,147.1,139.7,135.0,134.1,132.1,
130.2,126.1,125.5,118.7,110.8.
The data of the Enantiomeric excess of products therefrom are as follows：
19F NMR (470MHz, CDCl3)：δ -61.8 (s, 3F)
The theoretical calculation and experimental result that elementary analysis is carried out to product are as follows：
Anal.Calcd.For C12H7ClF3NO：C, 52.67；H, 2.58；N, 5.12；
Found：C, 52.66；H, 2.59；N, 5.11；
Embodiment 12
The synthesis of the chloro- 2- of 3- (2- pyridines epoxide) benzaldehyde
At room temperature, by palladium (5mol%), p-methyl benzenesulfonic acid (5mol%), 2- (2- pyridines epoxide) benzaldehyde
(0.4mmol, 1equiv), N- chlorosuccinimides (0.4mmol, 1equiv) stir 24h under 40 DEG C of reaction temperatures；Pass through
After thin-layer chromatography monitoring reaction terminates, 20mL ethyl acetate is added, then simple filtration spins off solvent, obtained through chromatographing post separation
To product (eluant, eluent：Petroleum ether: ether=97: 3), product is yellow liquid, and yield 54%, products weight is 25.2mg；
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 10.16 (s, 1H), 8.07 (s, 1H), 7.89 (d, J=7.5Hz, 1H), 7.79-
7.71 (m, 2H), 7.34 (t, J=8.0Hz, 1H), 7.14-7.02 (m, 2H)
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 189.0,171.0,163.4,156.5,147.7,139.9,135.5,
128.6,125.1,122.5,119.3,111.8.
The theoretical calculation and experimental result that elementary analysis is carried out to product are as follows：
Anal.Calcd.For C12H8ClNO2：C, 61.69；H, 3.45；N, 5.99；
Found：C, 61.68；H, 3.46；N, 5.98；
Embodiment 13
The synthesis of 2- (2,5- dichlorophenoxy) pyridine
At room temperature, by palladium (5mol%), p-methyl benzenesulfonic acid (5mol%), 2- (3- chlorophenoxies) pyridine
(0.4mmol, 1equiv), N- chlorosuccinimides (0.4mmol, 1equiv) stir 24h under 40 DEG C of reaction temperatures；Pass through
After thin-layer chromatography monitoring reaction terminates, 20mL ethyl acetate is added, then simple filtration spins off solvent, obtained through chromatographing post separation
To product (eluant, eluent：Petroleum ether: ether=97: 3), product is yellow liquid, and yield 81%, products weight is 76.2mg；
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.16 (d, J=4.0Hz, 1H), 7.74 (t, J=8.0Hz, 1H), 7.39 (d, J
=8.5Hz, 1H), 7.24-7.16 (m, 2H), 7.09-6.99 (m, 2H)
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 162.5,150.4,147.5,139.8,133.0,131.1,128.3,
126.2,124.2,119.0,111.3.
The theoretical calculation and experimental result that elementary analysis is carried out to product are as follows：
Anal.Calcd.For C11H7Cl2NO：C, 55.03；H, 2.94；N, 5.83；
Found：C, 55.02；H, 2.93；N, 5.84；
Embodiment 14
The synthesis of 2- (the bromo- 2- chlorophenoxies of 5-) pyridine
At room temperature, by palladium (5mol%), p-methyl benzenesulfonic acid (5mol%), 2- (3- bromobenzenes epoxide) pyridine
(0.4mmol, 1equiv), N- chlorosuccinimides (0.4mmol, 2equiv) stir 24h under 40 DEG C of reaction temperatures；Pass through
After thin-layer chromatography monitoring reaction terminates, 20mL ethyl acetate is added, then simple filtration spins off solvent, obtained through chromatographing post separation
To product (eluant, eluent：Petroleum ether: ether=97: 3), product is yellow liquid, and yield 88%, products weight is 99.4mg；
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.16 (s, 1H), 7.73 (t, J=7.5Hz, 1H), 7.38-7.29 (m, 3H)
(7.05-6.99 m, 2H)
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 162.5,150.5,147.5,139.8,139.7,131.5,129.1,
127.0,120.4,119.0,111.3.
The theoretical calculation and experimental result that elementary analysis is carried out to product are as follows：
Anal.Calcd.For C11H7BrClNO：C, 46.43；H, 2.48；N, 4.92；
Found：C, 46.44；H, 2.47；N, 4.93；
Embodiment 15
The synthesis of 2- (the 2- tert-butyl group -6- chlorophenoxies) pyridine
At room temperature, by palladium (5mol%), p-methyl benzenesulfonic acid (5mol%), 2- (2- tert-butyl benzenes epoxide) pyridine
(0.4mmol, 1equiv), N- chlorosuccinimides (0.4mmol, 1equiv) stir 24h under 40 DEG C of reaction temperatures；Pass through
After thin-layer chromatography monitoring reaction terminates, 20mL ethyl acetate is added, then simple filtration spins off solvent, obtained through chromatographing post separation
To product (eluant, eluent：Petroleum ether: ether=97: 3), product is yellow liquid, and yield 77%, products weight is 80.2mg；
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.08 (s, 1H), 7.62 (t, J=7.0Hz, 1H), 7.31-7.24 (m, 2H),
(s, the 9H) of 7.05 (t, J=8.0Hz, 1H), 6.90-6.84 (m, 2H), 1.24
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 162.0,147.1,146.6,143.7,138.3,127.4,124.9,
116.9,109.7,34.3,29.5,28.2.
The theoretical calculation and experimental result that elementary analysis is carried out to product are as follows：
Anal.Calcd.For C15H16ClNO：C, 68.83；H, 6.16；N, 5.35；
Found：C, 68.84；H, 6.15；N, 5.34；
Embodiment 16
(the 2- pyridines epoxide) -7 of chloro- 8,9,13,14- tetramethyls of (8R, 9S, 13S, 14S) -2- -3,8,9,11,12,13,
The synthesis of luxuriant and rich with fragrance -17 (14 hydrogen) ketone of 15,16- octahydro -6- hydrogen-cyclopenta [a]
At room temperature, by palladium (5mol%), p-methyl benzenesulfonic acid (5mol%), 2- estrone epoxide pyridines
(0.4mmol, 1equiv), N- chlorosuccinimides (0.4mmol, 1equiv) stir 24h under 40 DEG C of reaction temperatures；Pass through
After thin-layer chromatography monitoring reaction terminates, 20mL ethyl acetate is added, then simple filtration spins off solvent, obtained through chromatographing post separation
To product (eluant, eluent：Petroleum ether: ether=97: 3), product is yellow liquid, and yield 55%, products weight is 93.0mg；
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR (500MHz, CDCl3)：δ 8.20-8.16 (m, 1H), 7.73-7.66 (m, 1H), 6.99-6.88 (m, 3H),
4.17-4.04 (m, 1H), 3.03-0.88 (m, 24H)
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR (125MHz, CDCl3)：δ 172.4,147.7,139.4,137.8,135.3,127.4,126.5,
123.8,121.3,118.8,111.5,100.0,83.0,60.7,55.8,46.9,43.8,37.5,36.9,32.4,31.8,
29.2,26.4,25.4,15.8,14.2.
The theoretical calculation and experimental result that elementary analysis is carried out to product are as follows：
Anal.Calcd.For C26H30ClNO2：C, 73.65；H, 7.13；N, 3.30；
Found：C, 73.64；H, 7.12；N, 3.31；
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 2- (2- chlorophenoxies) pyridine compounds and their.
Embodiment 17-25
In addition to catalyst acetic acid palladium therein is replaced with into following palladium catalyst respectively, with highest products collection efficiency
The identical mode of embodiment 14 and implement embodiment 17-25 respectively, use the yield of palladium compound and corresponding product such as
Shown in table 1 below.
Table 1
| Numbering | Palladium catalyst | Reaction yield (%) |
| Embodiment 17 | PdCl2 | 44 |
| Embodiment 18 | Pd(PPh3)4 | Do not react |
| Embodiment 19 | PdI2 | 31 |
| Embodiment 20 | PdBr2 | 27 |
| Embodiment 21 | Pd(CH3CN)4(BF4)2 | 48 |
| Embodiment 22 | Pd(C6H5CN)2Cl2 | 50 |
| Embodiment 23 | Pd(acac)2 | 38 |
| Embodiment 24 | Pd(TFA)2 | 70 |
| Embodiment 25 | Pd(PPh3)2Cl2 | 51 |
It can be seen that by upper table 1, when using other palladium compounds, products collection efficiency is greatly lowered.Thus this is demonstrated
Catalyst acetic acid palladium used in invention has efficient catalytic performance for the reaction.
Embodiment 26-34
In addition to acid additive p-methyl benzenesulfonic acid therein is replaced with into following organic acid respectively, with highest product
The identical mode of embodiment 7 of yield and implement embodiment 26-34 respectively, use the yield of alkali cpd and corresponding product
It is as shown in table 2 below.
Table 2
| Numbering | Acid additive | Reaction yield (%) |
| Embodiment 26 | Acetic acid | 50 |
| Embodiment 27 | Propionic acid | 42 |
| Embodiment 28 | Butyric acid | 39 |
| Embodiment 29 | Pivalic acid | 28 |
| Embodiment 30 | Benzoic acid | 49 |
| Embodiment 31 | 4- nitrobenzoic acids | 20 |
| Embodiment 32 | Benzene sulfonic acid | 50 |
| Embodiment 33 | Trifluoroacetic acid | 14 |
| Embodiment 34 | Trifluoromethanesulfonic acid | Do not react |
It can be seen that by upper table 2, when using other acid additives, products collection efficiency is greatly lowered, and some oxidants
Do not react even.Thus demonstrate p-methyl benzenesulfonic acid used in the present invention as acid additive to the reaction system the most
Effectively.
Embodiment 35-45
In addition to organic solvent ethyl acetate therein is replaced with into following organic solvent respectively, with highest product
The identical mode of embodiment 1 of yield and implement embodiment 35-45 respectively, use the yield of organic solvent and corresponding product
It is as shown in the table.
Table 3
Can be seen that by upper table 3, when using other organic solvents, except in non-polar solven such as toluene, dichloroethanes and
N-hexane can be reacted, but yield is still significantly reduced；And there is no any production under the conditions of highly polar or even weak ligand solvent
Thing.This demonstrate that 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 i.e. using selected from palladium
Compound as catalyst (especially palladium), acid additive (especially p-methyl benzenesulfonic acid), suitable organic solvent (especially
Ethyl acetate) constituted recombination reaction system when, simple 2- phenoxypyridines and N- chlorosuccinimides can occurs
Phenyl ring c h bond chlorination and with high yield and high-purity synthesis obtain 2- (2- chlorophenoxies) pyridine compounds, be such change
The efficient quick synthesis of compound 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 preparation method and use of 2- (2- chlorophenoxies) pyridine compounds, it is characterised in that to be tied formula (I) Suo Shi
The 2- phenoxypyridines of structure is reaction raw materials with N- chlorosuccinimides, under nitrogen reaction atmosphere, is urged in transition metal palladium
Agent and acid additive are collectively promoted under effect, and the chlorination activated in reaction dissolvent by phenyl ring c h bond obtains formula
(II) 2- (2- chlorophenoxies) pyridine compounds shown in；
In formula (I) and (II), R is each independently selected from halogen, alkoxy, straight chained alkyl, branched alkyl, trifluoromethyl, trifluoro
Methyl mercapto, formoxyl, aldehyde radical, aryl or cyano group.
2. preparation method according to claim 1, it is characterised in that the palladium catalyst is organic palladium or inorganic palladium chemical combination
Thing；With molar amount, the consumption of the palladium catalyst is the 1-5% of the 2- phenoxypyridines consumption.
3. preparation method according to claim 2, it is characterised in that the inorganic palladium is that palladium bichloride or 10% palladium carbon are catalyzed
One kind in agent；The organic palladium is palladium, tetra-triphenylphosphine palladium, double (tricyclohexyl phosphine) palladiums, palladium diiodide, dibrominated
Palladium, four (acetonitrile) tetrafluoro boric acid palladiums, three (dibenzalacetone) two palladium, tetrachloro-palladium acid sodium, two (cyano group benzene) palladium chlorides, two
At least one of (acetonitrile) palladium chloride, two (acetylacetone,2,4-pentanedione) palladiums, palladium trifluoroacetate and double (triphenylphosphine) palladium chlorides, it is excellent
Elect palladium as.
4. preparation method according to claim 1, it is characterised in that the palladium catalyst is PdCl2、Pd(OAc)2、Pd
(PPh3)4、Pd(PCy3)2、PdI2、PdBr2、Pd(CH3CN)4(BF4)2、Na2PdCl4、Pd(C6H5CN)2Cl2、Pd(CH3CN)2Cl2、Pd(acac)2、Pd(TFA)2With Pd (PPh3)2Cl2At least one of, preferably Pd (OAc)2；With molar amount, the palladium
The consumption of catalyst is the 1-5% of 2- phenoxypyridines consumptions.
5. the preparation method as described in any one of Claims 1-4, it is characterised in that the acid additive be acetic acid, propionic acid,
Butyric acid, valeric acid, pivalic acid, benzoic acid, 4- nitrobenzoic acids, 2,6- dimethoxybenzoic acids, p-methyl benzenesulfonic acid, benzene sulfonic acid,
At least one of trifluoromethanesulfonic acid and trifluoroacetic acid, preferably p-methyl benzenesulfonic acid, with molar amount, the use of the acid additive
Amount and the 1-5% of 2- phenoxypyridines consumptions.
6. the preparation method as shown in any one of claim 1 to 5, it is characterised in that the reaction dissolvent is organic solvent, institute
State organic solvent in alcohol, ether, acid amides, chloralkane, aromatic hydrocarbon, dimethyl sulfoxide (DMSO), ester, heterocyclic arene, aliphatic hydrocarbon at least
It is a kind of.
7. the preparation method according to any one of claim 1 to 6, it is characterised in that the reaction dissolvent is organic solvent,
The organic solvent is dimethyl sulfoxide (DMSO), DMF, ethanol, polyethylene glycol, dichloromethane, ethyl acetate, pyrrole
Pyridine, n-hexane, the alkane of Isosorbide-5-Nitrae-dioxy six, 1,2- dichloroethanes, toluene, tetrahydrofuran, methanol, ether, carbon tetrachloride, dimethylbenzene,
At least one of benzene, chloroform, normal propyl alcohol, isopropanol, n-butanol, ethyl acetate.
8. the preparation method according to claim 1- to 7 any one, it is characterised in that the 2- phenoxypyridines and N- chlorine
Mol ratio for succimide is 1: 1-1: 5, preferably 1: 1.
9. the preparation according to any one of claim 1 to 8, it is characterised in that the temperature of the scope is 0-40 DEG C；It is described
The time of reaction is 15-30h.
10. a kind of 2- (2- chlorophenoxies) pyridine compounds, it is characterised in that by any one of claim 1 to 9 methods described system
It is standby to obtain.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104844399A (en) * | 2015-03-19 | 2015-08-19 | 浙江工业大学 | Method for synthetizing 2-fluoro phenol compound |
| CN105294583A (en) * | 2015-10-28 | 2016-02-03 | 同济大学 | Synthesizing method of 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid |
| CN105849102A (en) * | 2013-10-29 | 2016-08-10 | 生物马林药物股份有限公司 | N-(1-hydroxy-3-(pyrrolidinyl)propan-2-yl)pyrrolidine-3-carboxamide derivatives as glucosylceramide synthase inhibitors |
-
2017
- 2017-03-29 CN CN201710220499.0A patent/CN107011251B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105849102A (en) * | 2013-10-29 | 2016-08-10 | 生物马林药物股份有限公司 | N-(1-hydroxy-3-(pyrrolidinyl)propan-2-yl)pyrrolidine-3-carboxamide derivatives as glucosylceramide synthase inhibitors |
| CN104844399A (en) * | 2015-03-19 | 2015-08-19 | 浙江工业大学 | Method for synthetizing 2-fluoro phenol compound |
| CN105294583A (en) * | 2015-10-28 | 2016-02-03 | 同济大学 | Synthesizing method of 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid |
Non-Patent Citations (2)
| Title |
|---|
| FUJIKAWA, KANICHI等: "Studies on Herbicidal Activities of Phenoxypyridines", 《AGRICULTURAL AND BIOLOGICAL CHEMISTRY》 * |
| LOU, SHAO-JIE等: "Selective C-H Bond Fluorination of Phenols with a Removable Directing Group: Late-Stage Fluorination of 2-Phenoxyl Nicotinate Derivatives", 《ACS CATALYSIS》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113651681A (en) * | 2021-08-11 | 2021-11-16 | 中山大学 | Method for preparing aldehyde/ketone by breaking C-C bond |
| CN113651681B (en) * | 2021-08-11 | 2022-07-22 | 中山大学 | Method for preparing aldehyde/ketone by breaking C-C bond |
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