CN105330565B - Novel method for catalytically synthesizing cyanobenzene derivative through copper - Google Patents
Novel method for catalytically synthesizing cyanobenzene derivative through copper Download PDFInfo
- Publication number
- CN105330565B CN105330565B CN201510697605.5A CN201510697605A CN105330565B CN 105330565 B CN105330565 B CN 105330565B CN 201510697605 A CN201510697605 A CN 201510697605A CN 105330565 B CN105330565 B CN 105330565B
- Authority
- CN
- China
- Prior art keywords
- copper
- benzonitrile
- prepared
- ethoxys
- synthesizing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Abstract
The invention discloses a novel method for catalytically synthesizing a cyanobenzene derivative through copper. The method comprises the steps that a benzyl ether or benzaldehyde compound is used as a substrate and combined with a nitrogen source at certain temperature on the condition that copper salt is used as a catalyst to obtain the cyanobenzene derivative. Compared with traditional synthesis methods, the novel method includes only one step, the reaction time is short, the reaction condition is mild, and aftertreatment is simple. The substrate range is wide, both benzyl ether and benzaldehyde can be used as the substrate, it is not reported that ethers are used as the substrate for synthesizing a nitrile compound, no side reaction is produced when benzaldehyde is used as the substrate, and the product separation yield reaches 94% to the maximum degree.
Description
Technical field
The invention belongs to chemical synthesis, high-activity biological pharmaceutical intermediate study on the synthesis technical field, specifically a kind of benzene
The synthetic method of the synthetic method of 6-carbonitrile derivatives, i.e. 2- (2- ethoxys)-benzonitrile and its derivative.
Background technology
Nitrile compounds are very important industrial chemicals, are widely used in the fields such as chemical industry, medicine, agricultural chemicals and biology,
In synthetic fibers and plastics, plating, the quenching of steel etc. industrially also play the role of and its important.In the present invention, specific institute
The compound of synthesis is that 2- (2- ethoxys)-benzonitriles and its derivative are synthetic drug [o- bismuth (heterocycle) aryl]-[2-
(m- double (heterocycle) aryl-pyrrolidine -1- bases]-MIBK important intermediate, the medicine is used as the antagonism of orexin receptor
Agent, plays an important role in the metabolism of organism.Meanwhile, the compound be also synthesis 2- (sulfenyl) nicotine and
(S) important source material of -2- (pyridine -4- amino) propyl alcohol.Wherein the former is used as the inhibitor of 11 HSD1, and 11 HSD1 are sugar
The drug tar-get of urine disease and metabolic syndrome, is widely used in medicine and clinic at present.The latter is used as preparing fibrin ferment
The pharmaceutical intermediate of inhibitor, is widely used in terms of medicine, and thrombin inhibitor is used as treatment blood clotting and angiocarpy
The important medicine of disease, is also widely used in clinical treatment.In a word, 2- (the 2- hydroxyl second for being prepared by our synthetic method
Base)-benzonitrile and its derivative be very important medicine intermediate.
In terms of nitrile compounds are synthesized, there are many chemists to study this both at home and abroad, almost each year
There is similar research to be reported.In the middle of the research of synthesis nitrile compounds, substrate is that very have popularity, but
Some shortcomings are there is also in synthetic method.Reported respectively from benzyl halide and aldehyde compound at 2010 and 2012,
Synthesize cyano group using sodium azide as nitrogen source, although yield can reach more than 90%, however it is necessary that higher with toxicity
Sodium azide.2013, M.Bhanage groups using phenmethylol as substrate, ammonium formate as nitrogen source, it is achieved thereby that by alcohols
Compound is converted into the research of the nitrile compounds with cyano group, but the synthetic method need to carry out at a higher temperature and
Reaction time is more long.External certain chemical group proposes the road of synthesis 2- (2- ethoxys)-benzonitriles and its derivative within 2014
Line, but synthetic route is more long, it is necessary to 4 steps could be completed.
At home, the research in this regard of the pyronine seminar of Peking University is especially prominent, 2012 they developed from
Toluene is set out, and nitrile compounds have been collectively referred to as under the promotion of Cu, and then they have attempted with the alkene with aryl being raw material again
To synthesize cyano group, with trimethyl silicon substrate nitrine as nitrogen source, and yield higher is achieved.After this, they also go out from alkynyl
Hair has synthesized cyano group, and yield is also up to more than 80%；But, the accessory substance that this reaction is produced is more, does not meet Atom economy
Theory.Then they have studied from going out to send synthesis containing heteroatomic heterocyclic compound again.But, just synthesize substrate
Say, they reported before still not breaking through some, this has certain limitation for industrial application.
The report of the above-mentioned synthetic method being previously mentioned is made a general survey of, in the presence of some areas for improvement, such as environmental pollution
Seriously, reaction substrate is not enough extensively, reactions steps are more, accessory substance is more and severe reaction conditions etc..Although reaction substrate has virtue
Hydrocarbon compound, aldehydes, alcohols, heterocyclic etc., but from ether compound synthesis nitrile compounds but still beyond example.And
And, the exploration discovery in us constantly experiment, this synthetic method is equally applicable to compound of benzaldehyde category and directly prepares benzonitrile
Class compound.Therefore, the present invention opens a new route of synthesis in the synthesis for be applied to nitrile compounds, further opens up
The wide substrate spectrum for synthesizing nitrile compounds in the industrial production, is conducive to preparing this important industrial chemicals.
The content of the invention
The present invention provides a kind of novel method for synthesizing of benzonitrile derivative for the deficiency of above-mentioned synthetic method, is a kind of
Synthesize benzonitrile derivative by copper catalysis, with ether compound as substrate, as nitrogen source by taking trimethyl silicon substrate nitrine as an example, avoid
The larger sodium azide of toxicity, using base metal copper as catalyst, reaction condition is gentle, and the reaction time is short and reaction is only needed
A step is wanted to complete.Also, the exploration discovery in us constantly experiment, this synthetic method is equally applicable to compound of benzaldehyde category
Directly prepare benzonitrile class compound.Particular content is using benzylic ether or compound of benzaldehyde category as substrate, in depositing for nitrogen source
Under conditions, benzonitrile class compound is prepared by mantoquita catalysis.
Specific synthetic route is as follows：
Wherein R1It is hydrogen, methyl, halogen X (X=F, Cl, Br), the tert-butyl group, methoxyl group or phenyl ring, R2It is methyl or phenyl ring；
R3It is methoxyl group, nitro, phenyl ring, halogen X (X=Br, I).
To reach above-mentioned purpose, the technical solution adopted by the present invention is：It is with benzylic ether or compound of benzaldehyde category respectively
Substrate, as nitrogen source as a example by trimethyl silicon substrate nitrine, mantoquita is catalyst, a series of benzonitriles is obtained at a certain temperature and derives
Thing.Wherein mantoquita and the mol ratio of both nitrogen sources is 1：1~15, substrate is respectively 1 with the mol ratio of nitrogen source and mantoquita:1~15
With 1：1~15.
Described mantoquita is selected from as in copper acetate monohydrate, cuprous bromide, copper bromide, copper chloride, anhydrous cupric sulfate, copper powder
A kind of or its more than one various mixture；Preferably copper bromide.
Described nitrogen source is p-toluene sulfonyt azide, trimethyl silicon substrate nitrine, sodium azide, trimethyl silicon substrate diazomethane
In one kind；Preferably trimethyl silicon substrate nitrine.
Above, the copper of cuprous bromide is a valence state in described mantoquita, and the copper in copper powder is zero-valent state, remaining
Copper is all divalent state.
Described reaction temperature is 60~120 DEG C, and the reaction time is 2~12 hours, preferably 80 DEG C.
The inventive method is preferably：
For formula (1) step：Dissolved during benzylic ether is added into reaction dissolvent, be subsequently added a certain amount of trimethyl silicon substrate and fold
Nitrogen, preheats 2 minutes at 80 DEG C, is subsequently adding a certain amount of copper salt catalyst, and heating is anti-in being finally putting into 80 DEG C of oil bath pan
Answer 2~12 hours；After reaction terminates, system is cooled to room temperature, filtered, be then extracted with ethyl acetate, then respectively with water and
Saturated common salt is washed；The organic layer for obtaining, by column chromatography, obtains pure compound after drying, concentration：2- (2- hydroxyl second
Base)-benzonitrile.
For formula (2) step：Dissolved during benzaldehyde is added into reaction dissolvent, be subsequently added a certain amount of trimethyl silicon substrate and fold
Nitrogen, preheats 2 minutes at 80 DEG C, is subsequently adding a certain amount of copper salt catalyst, and heating is anti-in being finally putting into 80 DEG C of oil bath pan
Answer 2~10 hours；After reaction terminates, system is cooled to room temperature, filtered, be then extracted with ethyl acetate, then respectively with water and
Saturated common salt is washed；The organic layer for obtaining, by column chromatography, obtains pure compound after drying, concentration：Benzonitrile.
Described reaction dissolvent is toluene, dichloromethane, tetrahydrofuran, ethyl acetate, propyl acetate, acetone, butanone, second
One kind in nitrile, ether, benzene, dimethylbenzene, trimethylbenzene, n-hexane.
The beneficial effects of the invention are as follows：
1st, the present invention is developed with benzyl ethers compounds as initiation material, in the synthesis nitrile compounds reported before
In do not used.
2nd, compared with conventional synthetic method, reactions steps only have a step to the present invention, and the reaction time is shorter, reaction condition temperature
With and post processing is simple.
3rd, the substrate spectrum that the present invention is used is wider, including benzylic ether and benzaldehydes, and in benzaldehydes the bottom of as
Occur without side reaction when thing reacts, the separation yield of product is up to 94%.
Brief description of the drawings
Fig. 1 (a) is composed for the hydrogen of 2- prepared by embodiment 1 (2- ethoxys) benzonitrile, and (b) is composed for carbon；
Fig. 2 (a) is composed for the hydrogen of the fluoro- 2- of 5- prepared by embodiment 2 (2- ethoxys) benzonitrile, and (b) is composed for carbon；
Fig. 3 (a) is composed for the hydrogen of the fluoro- 2- of 6- prepared by embodiment 3 (2- ethoxys) benzonitrile, and (b) is composed for carbon；
Fig. 4 (a) is composed for the hydrogen of the chloro- 2- of 5- prepared by embodiment 4 (2- ethoxys) benzonitrile, and (b) is composed for carbon；
Fig. 5 (a) is composed for the hydrogen of the chloro- 2- of 6- prepared by embodiment 5 (2- ethoxys) benzonitrile, and (b) is composed for carbon；
Fig. 6 (a) is composed for the hydrogen of the bromo- 2- of 5- prepared by embodiment 6 (2- ethoxys) benzonitrile, and (b) is composed for carbon；
Fig. 7 (a) is composed for the hydrogen of the bromo- 2- of 6- prepared by embodiment 7 (2- ethoxys) benzonitrile, and (b) is composed for carbon；
Fig. 8 (a) is composed for the hydrogen of 2- prepared by embodiment 8 (1- hydroxyl -2- hydroxypropyls) benzonitrile, and (b) is composed for carbon；
Fig. 9 (a) is composed for the hydrogen of 3- prepared by embodiment 9 (2- hydroxypropyls) benzonitrile, and (b) is composed for carbon；
Figure 10 (a) is composed for the hydrogen of 2- prepared by embodiment 10 (2- ethoxys) 5- methyl benzonitriles, and (b) is composed for carbon；
Figure 11 (a) is composed for the hydrogen of 2- prepared by embodiment 11 (2- ethoxys) 6- methyl benzonitriles, and (b) is composed for carbon；
Figure 12 (a) is composed for the hydrogen of 2- prepared by embodiment 12 (2- ethoxys) 3,6- dimethyl benzene formonitrile HCNs, and (b) is composed for carbon；
Figure 13 (a) is composed for the hydrogen of the 5- tert-butyl groups -2- (2- ethoxys) benzonitrile prepared by embodiment 13, and (b) is composed for carbon；
Figure 14 (a) is composed for the hydrogen of 5- methoxyl groups -2- (2- ethoxys) benzonitrile prepared by embodiment 14, and (b) is composed for carbon；
Figure 15 (a) is composed for the hydrogen of 5- methoxyl groups -2- (2- ethoxys) benzonitrile prepared by embodiment 15, and (b) is composed for carbon；
Figure 16 (a) is composed for the hydrogen of 1- prepared by embodiment 16 (2- ethoxys) 2- naphthonitriles, and (b) is composed for carbon；
Figure 17 (a) is composed for the hydrogen of 4- methoxy benzonitriles prepared by embodiment 17, and (b) is composed for carbon；
Figure 18 (a) is composed for the hydrogen of 2- methoxy benzonitriles prepared by embodiment 18, and (b) is composed for carbon；
Figure 19 (a) is composed for the hydrogen of 2- nitrobenzonitriles prepared by embodiment 19, and (b) is composed for carbon；
Figure 20 (a) is composed for the hydrogen of 3- nitrobenzonitriles prepared by embodiment 20, and (b) is composed for carbon；
Figure 21 (a) is composed for the hydrogen of 4- nitrobenzonitriles prepared by embodiment 21, and (b) is composed for carbon；
Figure 22 (a) is composed for the hydrogen of 2- naphthonitriles prepared by embodiment 22, and (b) is composed for carbon；
Figure 23 (a) is composed for the hydrogen of 4- bromobenzylcyanides prepared by embodiment 23, and (b) is composed for carbon；
Figure 24 (a) is composed for the hydrogen of 2- iodobenzenes formonitrile HCN prepared by embodiment 24, and (b) is composed for carbon.
Specific embodiment
With reference to embodiment, the invention will be further described：
Embodiment 1：
Added in a round-bottomed flask heterochromatic full (1.0mmol), acetonitrile (2ml), trimethyl silicon substrate nitrine (3.0mmol),
Stirred 1-2 minutes in 80 DEG C of heating module, then add CuBr2(2.0mmol), then at 80 DEG C after system sealing
Lower heating response 3 hours, reaction is extracted with ethyl acetate after terminating, and by simple column chromatography, (eluant, eluent uses stone after concentration
Oily ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain product 2- (2- ethoxys) benzonitrile, yield is 85%.
As shown in Fig. 1 (a), the hydrogen spectrum of 2- prepared by embodiment 1 (2- ethoxys) benzonitrile：1H NMR(500MHz,
CDCl3) δ 7.64 (d, J=7.7Hz, 1H), 7.55 (td, J=7.7,1.1Hz, 1H), 7.42 (d, J=7.8Hz, 1H), 7.34
(t, J=7.6Hz, 1H), 3.93 (t, J=6.5Hz, 2H), 3.11 (t, J=6.5Hz, 2H), 2.06 (s, 1H)
As shown in Fig. 1 (b), the carbon spectrum of 2- prepared by embodiment 1 (2- ethoxys) benzonitrile：13C NMR(126MHz,
CDCl3)δ142.82,132.88,132.82,130.37,127.01,118.12,112.83,62.53,37.78.
Embodiment 2:
Add 5- fluorine heterochromatic full (1.0mmol) in a round-bottomed flask, acetonitrile (2ml), trimethyl silicon substrate nitrine
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain the fluoro- 2- of product 5- (2- ethoxys) benzene
Formonitrile HCN, yield is 80%.
As shown in Fig. 2 (a), the hydrogen spectrum of the fluoro- 2- of 5- prepared by embodiment 2 (2- ethoxys) benzonitrile：1H NMR
(500MHz,CDCl3) δ 7.42 (dd, J=8.6,5.3Hz, 1H), 7.36 (dd, J=8.0,2.7Hz, 1H), 7.28 (td, J=
8.2,2.7Hz, 1H), 3.94 (t, J=6.4Hz, 2H), 3.10 (t, J=6.4Hz, 2H), 1.77 (s, 1H)
As shown in Fig. 2 (b), the carbon spectrum of the fluoro- 2- of 5- prepared by embodiment 2 (2- ethoxys) benzonitrile：13C NMR
(126MHz,CDCl3)δ161.76,159.79,138.95,138.92,132.29,132.23,120.55,120.39,
119.50,119.31,62.53,62.52,36.97.
Mass spectrometric data is：HRMS(ESI)Calcd for C9H9FNO(M+H+):166.0668,found,166.0666.
Embodiment 3:
Add 6- fluorine heterochromatic full (1.0mmol) in a round-bottomed flask, acetonitrile (2ml), trimethyl silicon substrate nitrine
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain the fluoro- 2- of product 8- (2- ethoxys) benzene
Formonitrile HCN, yield is 80%.
As shown in Fig. 3 (a), the hydrogen spectrum of the fluoro- 2- of 6- prepared by embodiment 3 (2- ethoxys) benzonitrile：1H NMR
(500MHz,CDCl3) δ 7.65 (dd, J=8.6,5.5Hz, 1H), 7.15 (dd, J=9.2,2.5Hz, 1H), 7.04 (td, J=
8.3,2.5Hz, 1H), 3.96 (t, J=6.3Hz, 2H), 3.16-2.99 (m, 2H), 1.69 (d, J=6.2Hz, 1H)
As shown in Fig. 3 (a), the carbon spectrum of the fluoro- 2- of 6- prepared by embodiment 3 (2- ethoxys) benzonitrile：13C NMR
(126MHz,CDCl3)δ165.95,163.91,146.42,146.35,135.16,135.09,117.90,117.72,
117.45,114.87,114.69,62.21,37.63,37.62.
Mass spectrometric data is：HRMS(ESI)Calcd for C9H8FNONa(M+Na+):188.0488,found,
188.0484.
Embodiment 4:
Add 5- chlorine heterochromatic full (1.0mmol) in a round-bottomed flask, acetonitrile (2ml), trimethyl silicon substrate nitrine
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain the chloro- 2- of product 5- (2- ethoxys) benzene
Formonitrile HCN, yield is 70%.
As shown in Fig. 4 (a), the hydrogen spectrum of the chloro- 2- of 5- prepared by embodiment 4 (2- ethoxys) benzonitrile：1H NMR
(500MHz,CDCl3) δ 7.63 (d, J=2.2Hz, 1H), 7.53 (dd, J=8.4,2.2Hz, 1H), 7.38 (d, J=8.4Hz,
1H), (s, the 1H) of 3.94 (t, J=6.4Hz, 2H), 3.09 (t, J=6.4Hz, 2H), 1.77
As shown in Fig. 4 (b), the carbon spectrum of the chloro- 2- of 5- prepared by embodiment 4 (2- ethoxys) benzonitrile：13C NMR
(126MHz,CDCl3)δ141.41,133.12,132.93,132.32,131.77,116.87,114.35,62.37,37.14.
Mass spectrometric data is：HRMS(ESI)Calcd for C9H8ClNONa(M+Na+):204.0192,found,
204.0189.
Embodiment 5:
Add 6- chlorine heterochromatic full (1.0mmol) in a round-bottomed flask, acetonitrile (2ml), trimethyl silicon substrate nitrine
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain the chloro- 2- of product 6- (2- ethoxys) benzene
Formonitrile HCN, yield is 65%.
As shown in Fig. 5 (a), the hydrogen spectrum of the chloro- 2- of 6- prepared by embodiment 5 (2- ethoxys) benzonitrile：1H NMR
(500MHz,CDCl3) δ 7.58 (d, J=8.3Hz, 1H), 7.43 (d, J=2.0Hz, 1H), 7.33 (dd, J=8.3,2.0Hz,
1H), (d, J=6.7Hz, the 1H) of 3.94 (dd, J=7.8,4.8Hz, 2H), 3.07 (t, J=6.3Hz, 2H), 1.85
As shown in Fig. 5 (b), the carbon spectrum of the chloro- 2- of 6- prepared by embodiment 5 (2- ethoxys) benzonitrile：13C NMR
(126MHz,CDCl3)δ144.81,139.38,133.91,130.72,127.55,117.44,111.28,62.21,37.49.
Mass spectrometric data is：HRMS(ESI)Calcd for C9H8ClNONa(M+Na+):204.0192,found,
204.0192.
Embodiment 6:
Add 5- bromines heterochromatic full (1.0mmol) in a round-bottomed flask, acetonitrile (2ml), trimethyl silicon substrate nitrine
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain the bromo- 2- of product 5- (2- ethoxys) benzene
Formonitrile HCN, yield is 60%.
As shown in Fig. 6 (a), the hydrogen spectrum of the bromo- 2- of 5- prepared by embodiment 6 (2- ethoxys) benzonitrile：1H NMR
(500MHz,CDCl3) δ 7.78 (d, J=2.1Hz, 1H), 7.68 (dd, J=8.3,2.1Hz, 1H), 7.32 (d, J=8.3Hz,
1H), (s, the 1H) of 3.94 (t, J=6.4Hz, 2H), 3.07 (t, J=6.4Hz, 2H), 1.79
As shown in Fig. 6 (b), the carbon spectrum of the bromo- 2- of 5- prepared by embodiment 6 (2- ethoxys) benzonitrile：13C NMR
(126MHz,CDCl3)δ141.89,136.02,135.18,131.97,120.36,116.73,114.69,62.29,37.22.
Mass spectrometric data is：HRMS(ESI)Calcd for C9H9BrNO(M+H+):225.9868,found,225.9865.
Embodiment 7
Add 6- bromines heterochromatic full (1.0mmol) in a round-bottomed flask, acetonitrile (2ml), trimethyl silicon substrate nitrine
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain the bromo- 2- of product 6- (2- ethoxys) benzene
Formonitrile HCN, yield is 87%.
As shown in Fig. 7 (a), the hydrogen spectrum of the bromo- 2- of 6- prepared by embodiment 7 (2- ethoxys) benzonitrile：1H NMR
(500MHz,CDCl3) δ 7.62 (s, 1H), 7.52 (d, J=1.4Hz, 2H), 3.99-3.96 (m, 2H), 3.09 (t, J=
6.3Hz,2H),1.66(s,1H).
As shown in Fig. 7 (b), the carbon spectrum of the bromo- 2- of 6- prepared by embodiment 7 (2- ethoxys) benzonitrile：13C NMR
(126MHz,CDCl3)δ144.78,133.90,133.65,130.49,127.91,117.47,111.81,62.26,37.44.
Mass spectrometric data is：HRMS(ESI)Calcd for C9H9BrNO(M+H+):225.9868,found,225.9876.
Embodiment 8:
Add 4- methyl heterochromatic full (1.0mmol) in a round-bottomed flask, acetonitrile (2ml), trimethyl silicon substrate nitrine
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain product 2- (1- hydroxyl -2- hydroxypropyls)
Benzonitrile, yield is 50%.
As shown in Fig. 8 (a), the hydrogen spectrum of 2- prepared by embodiment 8 (1- hydroxyl -2- hydroxypropyls) benzonitrile：1H NMR
(500MHz,CDCl3) δ 7.57 (dd, J=7.7,1.1Hz, 1H), 7.50 (td, J=7.8,1.3Hz, 1H), 7.35 (d, J=
7.9Hz, 1H), 7.25 (td, J=7.6,1.0Hz, 1H), 3.73 (d, J=6.6Hz, 2H), 3.37 (dd, J=13.6,6.8Hz,
1H), 1.64 (s, 1H), 1.27 (d, J=7.0Hz, 3H)
As shown in Fig. 8 (b), the carbon spectrum of 2- prepared by embodiment 8 (1- hydroxyl -2- hydroxypropyls) benzonitrile：13C NMR
(126MHz,CDCl3)δ146.83,132.02,132.01,125.96,125.94,117.17,111.85,66.52,39.52,
16.12.
Mass spectrometric data is：HRMS(ESI)Calcd for C10H12NO(M+H+):162.0919,found,162.0926.
Embodiment 9
Add 3- methyl heterochromatic full (1.0mmol) in a round-bottomed flask, acetonitrile (2ml), trimethyl silicon substrate nitrine
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain product 3- (2- hydroxypropyls) benzonitrile,
Yield is 67%.
As shown in Fig. 9 (a), the hydrogen spectrum of 3- prepared by embodiment 9 (2- hydroxypropyls) benzonitrile：1H NMR(500MHz,
CDCl3) δ 7.66 (dd, J=7.7,1.1Hz, 1H), 7.56 (td, J=7.7,1.3Hz, 1H), 7.43-7.39 (m, 1H), 7.36
(td, J=7.6,1.1Hz, 1H), 4.16 (ddd, J=7.8,6.2,4.8Hz, 1H), 3.01 (ddd, J=21.6,13.7,
6.3Hz, 2H), 1.68 (s, 1H), 1.32 (d, J=6.2Hz, 3H)
As shown in Fig. 9 (b), the carbon spectrum of 3- prepared by embodiment 9 (2- hydroxypropyls) benzonitrile：13C NMR(126MHz,
CDCl3)δ142.71,132.90,132.70,130.79,127.02,118.30,113.10,68.33,44.03,23.26.
Mass spectrometric data is：HRMS(ESI)Calcd for C10H12NO(M+H+):162.0919,found,162.0927.
Embodiment 10
Add 7- methyl heterochromatic full (1.0mmol) in a round-bottomed flask, acetonitrile (2ml), trimethyl silicon substrate nitrine
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain product 2- (2- ethoxys) 5- methylbenzenes
Formonitrile HCN, yield is 60%.
As shown in Figure 10 (a), the hydrogen spectrum of 2- prepared by embodiment 10 (2- ethoxys) 5- methyl benzonitriles：1H NMR
(500MHz,CDCl3) δ 7.44 (s, 1H), 7.34 (dd, J=7.9,1.1Hz, 1H), 7.28 (d, J=7.9Hz, 1H), 3.90
(t, J=6.5Hz, 2H), 3.05 (t, J=6.5Hz, 2H), 2.35 (s, 3H), 1.77 (s, 1H)
As shown in Figure 10 (b), the carbon spectrum of 2- prepared by embodiment 10 (2- ethoxys) 5- methyl benzonitriles：13C NMR
(126MHz,CDCl3)δ139.67,137.05,133.77,133.15,130.25,118.30,112.62,62.72,37.33,
20.69.
Mass spectrometric data is：HRMS(ESI)Calcd for C10H12NO(M+H+):162.0919,found,162.0912.
Embodiment 11:
Add 8- methyl heterochromatic full (1.0mmol) in a round-bottomed flask, acetonitrile (2ml), trimethyl silicon substrate nitrine
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain product 2- (2- ethoxys) 6- methylbenzenes
Formonitrile HCN, yield is 70%.
As shown in Figure 11 (a), the hydrogen spectrum of 2- prepared by embodiment 11 (2- ethoxys) 6- methyl benzonitriles：1H NMR
(500MHz,CDCl3) δ 7.52 (d, J=7.9Hz, 1H), 7.20 (s, 1H), 7.13 (d, J=7.9Hz, 1H), 3.96-3.84
(m, 2H), 3.10-2.96 (m, 2H), 2.43 (dd, J=60.8,42.4Hz, 3H), 2.07 (d, J=27.5Hz, 1H)
As shown in Figure 11 (b), the carbon spectrum of 2- prepared by embodiment 11 (2- ethoxys) 6- methyl benzonitriles：13C NMR
(126MHz,CDCl3)δ143.79,142.60,132.79,132.32,131.15,128.19,127.89,127.50,
118.50,109.67,62.62,62.60,38.08,37.74,21.83,20.87.
Mass spectrometric data is：HRMS(ESI)Calcd for C10H12NO(M+H+):162.0919,found,162.0912.
Embodiment 12:
Add 5,8- dimethyl heterochromatic full (1.0mmol) in a round-bottomed flask, acetonitrile (2ml), trimethyl silicon substrate nitrine
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain product 2- (2- ethoxys) 3,6- diformazans
Base benzonitrile, yield is 38%.
As shown in Figure 12 (a), the hydrogen spectrum of 2- prepared by embodiment 12 (2- ethoxys) 3,6- dimethyl benzene formonitrile HCNs：1H NMR
(500MHz,CDCl3) δ 7.26 (d, J=7.8Hz, 1H), 7.08 (d, J=7.8Hz, 1H), 3.88 (t, J=7.0Hz, 2H),
(s, the 1H) of 3.15 (t, J=7.0Hz, 2H), 2.50 (s, 3H), 2.36 (s, 3H), 1.79
As shown in Figure 12 (b), the carbon spectrum of 2- prepared by embodiment 12 (2- ethoxys) 3,6- dimethyl benzene formonitrile HCNs：13C NMR
(126MHz,CDCl3)δ140.57,140.08,135.06,134.39,128.12,117.88,114.02,62.09,35.34,
20.59,19.39.
Mass spectrometric data is：HRMS(ESI)Calcd for C11H14NO(M+H+):176.1075,found,176.1074.
Embodiment 13:
Add the 7- tert-butyl groups heterochromatic full (1.0mmol) in a round-bottomed flask, acetonitrile (2ml), trimethyl silicon substrate nitrine
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain the product 5- tert-butyl groups -2- (2- hydroxyl second
Base) benzonitrile, yield is 68%.
As shown in Figure 13 (a), the hydrogen spectrum of the 5- tert-butyl groups -2- (2- ethoxys) benzonitrile prepared by embodiment 13：1H NMR
(500MHz,CDCl3) δ 7.66 (d, J=2.1Hz, 1H), 7.58 (dd, J=8.2,2.1Hz, 1H), 7.35 (d, J=8.2Hz,
1H), (s, the 9H) of 3.95 (t, J=6.5Hz, 2H), 3.09 (t, J=6.5Hz, 2H), 1.66 (s, 1H), 1.34
As shown in Figure 13 (b), the carbon spectrum of the 5- tert-butyl groups -2- (2- ethoxys) benzonitrile prepared by embodiment 13：13C NMR
(126MHz,CDCl3)δ150.37,139.59,130.20,130.11,129.85,118.62,112.48,62.72,37.27,
34.60,31.05.
Mass spectrometric data is：HRMS(ESI)Calcd for C13H18NO(M+H+):204.1388,found,204.1394.
Embodiment 14:
Add 7- methoxyl groups heterochromatic full (1.0mmol) in a round-bottomed flask, acetonitrile (2ml), trimethyl silicon substrate nitrine
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain product 5- methoxyl groups -2- (2- hydroxyl second
Base) benzonitrile, yield is 64%.
As shown in Figure 14 (a), the hydrogen spectrum of 5- methoxyl groups -2- (2- ethoxys) benzonitrile prepared by embodiment 14：1H NMR
(500MHz,CDCl3) δ 7.34 (d, J=2.1Hz, 1H), 7.05 (dd, J=8.3,2.1Hz, 1H), 6.77 (d, J=8.3Hz,
1H), (s, the 1H) of 3.80 (s, 2H), 3.74 (t, J=6.5Hz, 2H), 2.70 (t, J=6.5Hz, 2H), 1.60
As shown in Figure 14 (b), the carbon spectrum of 5- methoxyl groups -2- (2- ethoxys) benzonitrile prepared by embodiment 14：13C NMR
(126MHz,CDCl3)δ153.48,132.66,131.17,128.00,112.99,110.97,110.60,62.49,55.25,
36.82.
Mass spectrometric data is：HRMS(ESI)Calcd for C10H12NO2(M+H+):178.0868,found,178.0854.
Embodiment 15:
3,4- dihydro -1H- benzos [h] heterochromatic full (1.0mmol), acetonitrile (2ml), trimethyl are added in a round-bottomed flask
Silicon substrate nitrine (3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then
The system sealing after at 80 DEG C heating response 3 hours, reaction terminate after be extracted with ethyl acetate, after concentration pass through simple post
Chromatography (eluant, eluent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) is that can obtain product 1- (2- ethoxys)
1- naphthonitriles, yield is 43%.
As shown in Figure 15 (a), the hydrogen spectrum of 5- methoxyl groups -2- (2- ethoxys) benzonitrile prepared by embodiment 15：1H NMR
(500MHz,CDCl3) δ 8.22 (d, J=8.4Hz, 1H), 8.01 (d, J=8.4Hz, 1H), 7.89 (d, J=8.1Hz, 1H),
7.70-7.65 (m, 1H), 7.57 (t, J=7.5Hz, 1H), 7.48 (t, J=7.0Hz, 1H), 4.03 (t, J=6.5Hz, 2H),
3.31 (t, J=6.5Hz, 2H), 1.69 (s, 1H)
As shown in Figure 15 (b), the carbon spectrum of 5- methoxyl groups -2- (2- ethoxys) benzonitrile prepared by embodiment 15：13C NMR
(126MHz,CDCl3)δ143.74,132.90,131.65,128.69,128.44,127.33,127.00,125.11,
117.07,109.79,62.86,38.61.
Mass spectrometric data is：HRMS(ESI)Calcd for C13H12NO(M+H+):198.0919,found,198.0913.
Embodiment 16:
Isosorbide-5-Nitrae-dihydro -2H- benzos [f] heterochromatic full (1.0mmol), acetonitrile (2ml), trimethyl are added in a round-bottomed flask
Silicon substrate nitrine (3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then
The system sealing after at 80 DEG C heating response 3 hours, reaction terminate after be extracted with ethyl acetate, after concentration pass through simple post
Chromatography (eluant, eluent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) is that can obtain product 1- (2- ethoxys)
2- naphthonitriles, yield is 46%.
As shown in Figure 16 (a), the hydrogen spectrum of 1- prepared by embodiment 16 (2- ethoxys) 2- naphthonitriles：1H NMR(500MHz,
CDCl3) δ 8.18 (dd, J=5.4,4.2Hz, 1H), 7.91-7.87 (m, 1H), 7.80 (d, J=8.5Hz, 1H), 7.66-7.62
(m, 1H), 7.59 (d, J=8.5Hz, 1H), 4.03 (t, J=6.9Hz, 1H), 4.03 (t, J=6.9Hz, 2H), 3.64 (t, J=
6.9Hz,2H),1.83(s,1H).
As shown in Figure 16 (b), the carbon spectrum of 1- prepared by embodiment 16 (2- ethoxys) 2- naphthonitriles：13C NMR(126MHz,
CDCl3)δ142.00,135.08,131.49,129.01,128.64,128.11,127.73,126.66,124.81,77.32,
77.06,76.81,62.83,34.83.
Mass spectrometric data is：HRMS(ESI)Calcd for C13H11NONa(M+Na+):220.0738,found,
198.0913.
Embodiment 17
4-methoxybenzaldehyde (1.0mmol), acetonitrile (2ml), trimethyl silicon substrate nitrine are added in a round-bottomed flask
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain product 4- methoxy benzonitriles, yield
It is 94%.
As shown in Figure 17 (a), the hydrogen spectrum of 4- methoxy benzonitriles prepared by embodiment 17：1H NMR(500MHz,CDCl3)δ
(s, the 3H) of 7.59 (d, J=8.9Hz, 2H), 6.95 (d, J=8.9Hz, 2H), 3.86
As shown in Figure 17 (b), the carbon spectrum of 4- methoxy benzonitriles prepared by embodiment 17：13C NMR(126MHz,CDCl3)
δ162.86,133.99,119.25,114.76,103.97,77.32,77.06,76.81,55.56.
Embodiment 18
Benzaldehyde,2-methoxy (1.0mmol), acetonitrile (2ml), trimethyl silicon substrate nitrine are added in a round-bottomed flask
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain product 2- methoxy benzonitriles, yield
It is 76%.
As shown in Figure 18 (a), the hydrogen spectrum of 2- methoxy benzonitriles prepared by embodiment 18：1H NMR(500MHz,CDCl3)δ
(d, J=4.5Hz, the 3H) of 7.67-7.52 (m, 2H), 7.04-6.85 (m, 2H), 3.93
As shown in Figure 18 (b), the carbon spectrum of 2- methoxy benzonitriles prepared by embodiment 18：13C NMR(126MHz,CDCl3)
δ161.25,137.28,135.85,134.42,133.78,120.78,113.06,111.29,56.01.
Embodiment 19:
2- nitrobenzaldehydes (1.0mmol), acetonitrile (2ml), trimethyl silicon substrate nitrine are added in a round-bottomed flask
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain product 2- nitrobenzonitriles, yield is
74%.
As shown in Figure 19 (a), the hydrogen spectrum of 2- nitrobenzonitriles prepared by embodiment 19：1H NMR(500MHz,CDCl3)δ
(m, the 2H) of 8.36 (dd, J=6.1,3.4Hz, 1H), 7.98-7.93 (m, 1H), 7.89-7.83
As shown in Figure 19 (b), the carbon spectrum of 2- nitrobenzonitriles prepared by embodiment 19：13C NMR(126MHz,CDCl3)δ
135.64,134.37,133.76,125.61,114.98,108.10.
Embodiment 20:
3- nitrobenzaldehydes (1.0mmol), acetonitrile (2ml), trimethyl silicon substrate nitrine are added in a round-bottomed flask
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain product 3- nitrobenzonitriles, yield is
85%.
As shown in Figure 20 (a), the hydrogen spectrum of 3- nitrobenzonitriles prepared by embodiment 20：1H NMR(500MHz,CDCl3)δ
(t, J=8.0Hz, the 1H) of 8.56-8.53 (m, 1H), 8.50-8.47 (m, 1H), 8.01 (d, J=7.7Hz, 1H), 7.75
As shown in Figure 20 (b), the carbon spectrum of 3- nitrobenzonitriles prepared by embodiment 20：13C NMR(126MHz,CDCl3)δ
137.61,130.68,127.55,127.25,116.54,114.17.
Embodiment 21:
4- nitrobenzaldehydes (1.0mmol), acetonitrile (2ml), trimethyl silicon substrate nitrine are added in a round-bottomed flask
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain product 4- nitrobenzonitriles, yield is
90%.
As shown in Figure 21 (a), the hydrogen spectrum of 4- nitrobenzonitriles prepared by embodiment 21：1H NMR(500MHz,CDCl3)δ
8.39–8.35(m,2H),7.93–7.86(m,2H).
As shown in Figure 21 (b), the carbon spectrum of 4- nitrobenzonitriles prepared by embodiment 21：13C NMR(126MHz,CDCl3)δ
133.50,124.32,118.36,116.82.
Embodiment 22
2- naphthaldehydes (1.0mmol), acetonitrile (2ml), trimethyl silicon substrate nitrine are added in a round-bottomed flask
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain product 2- naphthonitriles, yield is 84%.
As shown in Figure 22 (a), the hydrogen spectrum of 2- naphthonitriles prepared by embodiment 22：1H NMR(500MHz,CDCl3)δ8.22
(s,1H),7.93–7.87(m,3H),7.67–7.57(m,3H).
As shown in Figure 22 (b), the carbon spectrum of 2- naphthonitriles prepared by embodiment 22：13C NMR(126MHz,CDCl3)δ
134.66,134.17,132.26,129.21,129.06,128.43,128.07,127.67,126.36,119.27,109.40.
Embodiment 23:
4- bromobenzaldehydes (1.0mmol), acetonitrile (2ml), trimethyl silicon substrate nitrine are added in a round-bottomed flask
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain product 4- bromobenzylcyanides, yield is
68%.
As shown in Figure 23 (a), the hydrogen spectrum of 4- bromobenzaldehydes prepared by embodiment 23：1H NMR(500MHz,CDCl3)δ7.63
(dt, J=7.4,3.7Hz, 2H), 7.54-7.50 (m, 2H)
As shown in Figure 23 (b), the carbon spectrum of 4- bromobenzylcyanides prepared by embodiment 23：13C NMR(126MHz,CDCl3)δ
133.42,132.66,128.03,118.07,111.26.
Embodiment 24:
2- benzaldehyde iodines (1.0mmol), acetonitrile (2ml), trimethyl silicon substrate nitrine are added in a round-bottomed flask
(3.0mmol), stirs 1-2 minutes in 80 DEG C of heating module, then adds CuBr2(2.0mmol), then the system is close
It is honored as a queen heating response 3 hours at 80 DEG C, reaction is extracted with ethyl acetate after terminating, and (is washed by simple column chromatography after concentration
De- agent uses petroleum ether (60~90 DEG C) and the mixed solvent of ethyl acetate) it is that can obtain product 2- iodobenzene formonitrile HCNs, yield is
68%.
As shown in Figure 24 (a), the hydrogen spectrum of 2- iodobenzenes formonitrile HCN prepared by embodiment 24：1H NMR(500MHz,CDCl3)δ
7.95-7.92 (m, 1H), 7.62 (dd, J=7.8,1.6Hz, 1H), 7.47 (td, J=7.7,1.1Hz, 1H), 7.30 (td, J=
7.9,1.6Hz,1H).
As shown in Figure 24 (b), the carbon spectrum of 2- iodobenzenes formonitrile HCN prepared by embodiment 24：13C NMR(126MHz,CDCl3)δ
139.58,134.28,133.70,128.30,120.69,119.33,98.41.
Embodiment 25:
Trimethyl silicon substrate nitrine in embodiment 1 is replaced by p-toluene sulfonyt azide, other experiment conditions are constant, are prepared into
To 2- (2- ethoxys) benzonitrile, yield is 77%.
Embodiment 26
Trimethyl silicon substrate nitrine in embodiment 1 is replaced by sodium azide, other experiment conditions are constant, prepare 2-
(2- ethoxys) benzonitrile, yield is 73%.
Embodiment 27
Trimethyl silicon substrate nitrine in embodiment 17 is replaced by trimethyl silicon substrate diazomethane, other experiment conditions are constant,
4- methoxy benzonitriles are prepared, yield is 80%.
Embodiment 28
Copper bromide in embodiment 1 is replaced by copper acetate monohydrate, solvent acetonitrile is replaced by toluene, and the reaction time is 2 small
When, other experiment conditions are constant, prepare 2- (2- ethoxys) benzonitrile, and yield is 62%.
Embodiment 29
Copper bromide in embodiment two is replaced by cuprous bromide, solvent acetonitrile is replaced by dichloromethane, and the reaction time is 10
Hour, other experiment conditions are constant, prepare the fluoro- 2- of 5- (2- ethoxys) benzonitrile, and yield is 70%.
Embodiment 30
Copper bromide in embodiment 3 is replaced by copper chloride, solvent acetonitrile is replaced by benzene, and temperature is changed into 60 DEG C from 80 DEG C, its
His experiment condition is constant, prepares the fluoro- 2- of 6- (2- ethoxys) benzonitrile, and yield is 59%.
Embodiment 31
Copper bromide in embodiment 3 is replaced by anhydrous cupric sulfate, solvent acetonitrile is replaced by acetone, and temperature is changed into from 80 DEG C
100 DEG C, other experiment conditions are constant, prepare the fluoro- 2- of 6- (2- ethoxys) benzonitrile, and yield is 73%.
Embodiment 32
Copper bromide in embodiment 4 is replaced by copper powder, solvent acetonitrile is replaced by trimethylbenzene, and temperature is changed into 120 DEG C from 80 DEG C,
Other experiment conditions are constant, prepare the chloro- 2- of 5- (2- ethoxys) benzonitrile, and yield is 67%.
Embodiment 33
Copper bromide in embodiment 4 is replaced by cuprous bromide, cuprous bromide addition is changed to 1mmol, trimethyl silicon substrate
Nitrine addition is changed to 15mmol, and solvent acetonitrile is replaced by tetrahydrofuran, and the reaction time is 12 hours, and other experiment conditions are not
Become, prepare the chloro- 2- of 5- (2- ethoxys) benzonitrile, yield is 65%
Embodiment 34
Copper bromide in embodiment 4 is replaced by copper bromide and copper chloride, copper bromide addition is changed to 5mmol, copper chloride
Addition is changed to 10mmol, and trimethyl silicon substrate nitrine addition is changed to 15mmol, and solvent acetonitrile is replaced by ethyl acetate, its
His experiment condition is constant, prepares the chloro- 2- of 5- (2- ethoxys) benzonitrile, and yield is 73%
Embodiment 35
Copper bromide addition in embodiment 4 is changed to 1mmol, trimethyl silicon substrate nitrine addition is changed to 1.0mmol,
Solvent acetonitrile is replaced by ether, and other experiment conditions are constant, prepares the chloro- 2- of 5- (2- ethoxys) benzonitrile, and yield is
58%.
The present invention develops isochroman compounds for initiation material, and benzene is directly prepared with the azide compounds for providing nitrogen source
The method of formonitrile HCN analog derivative class compound, compared with conventional synthetic method, present invention uses ether compound as conjunction
Into substrate, and reactions steps only have a step, and post processing is simple, and reaction condition is greatly gentle, are a kind of novelties, simply, efficiently close
Into the synthetic method of benzonitrile derivative.
Above-described embodiment is not that, for limitation of the invention, the present invention is not limited only to above-described embodiment, as long as meeting
Application claims, belong to protection scope of the present invention.
Claims (8)
1. a kind of novel method for synthesizing benzonitrile derivative by copper catalysis, it is characterised in that the method is with benzyl ethers chemical combination
Thing is substrate, in the case where mantoquita is catalysts conditions, prepares benzonitrile derivative with reference to nitrogen source at a certain temperature, specifically
Synthetic route is as follows：
Wherein R1It is hydrogen, methyl, halogen F, halogen Cl, halogen Br, the tert-butyl group, methoxyl group or phenyl ring, R2It is methyl or phenyl ring.
2. a kind of novel method for synthesizing benzonitrile derivative by copper catalysis as claimed in claim 1, it is characterised in that mantoquita
It is 1 with the mol ratio of nitrogen source：1~15；Substrate is respectively 1 with nitrogen source, the mol ratio of mantoquita：1~15 and 1：1~15.
3. a kind of novel method for synthesizing benzonitrile derivative by copper catalysis as claimed in claim 1, it is characterised in that described
Mantoquita be selected from as a kind of or many in copper acetate monohydrate, cuprous bromide, copper bromide, copper chloride, anhydrous cupric sulfate, copper powder
Plant mixture.
4. a kind of novel method for synthesizing benzonitrile derivative by copper catalysis as claimed in claim 1, it is characterised in that described
Nitrogen source be the one kind in p-toluene sulfonyt azide, trimethyl silicon substrate nitrine, sodium azide, trimethyl silicon substrate diazomethane.
5. a kind of novel method for synthesizing benzonitrile derivative by copper catalysis as claimed in claim 1, it is characterised in that described
Reaction temperature be 60~120 DEG C, the reaction time be 2~12 hours.
6. a kind of novel method for synthesizing benzonitrile derivative by copper catalysis as claimed in claim 5, it is characterised in that described
Reaction temperature be 80 DEG C.
7. a kind of novel method for synthesizing benzonitrile derivative by copper catalysis as claimed in claim 1, it is characterised in that the party
Method is dissolved during benzylic ether is added into reaction dissolvent, is subsequently added a certain amount of trimethyl silicon substrate nitrine, and 2 points are preheated at 80 DEG C
Clock, is subsequently adding a certain amount of copper salt catalyst, is finally putting into heating response 2~12 hours in 80 DEG C of oil bath pan；Reaction knot
Shu Hou, room temperature is cooled to by system, filtering, is then extracted with ethyl acetate, then respectively with water and saturated common salt washing；Obtain
Organic layer, by column chromatography, obtains pure compound after drying, concentration：2- (2- ethoxys)-benzonitrile.
8. a kind of novel method for synthesizing benzonitrile derivative by copper catalysis as claimed in claim 7, it is characterised in that described
Reaction dissolvent for toluene, dichloromethane, tetrahydrofuran, ethyl acetate, propyl acetate, acetone, butanone, acetonitrile, ether, benzene,
One kind in dimethylbenzene, trimethylbenzene, n-hexane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510697605.5A CN105330565B (en) | 2015-10-23 | 2015-10-23 | Novel method for catalytically synthesizing cyanobenzene derivative through copper |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510697605.5A CN105330565B (en) | 2015-10-23 | 2015-10-23 | Novel method for catalytically synthesizing cyanobenzene derivative through copper |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105330565A CN105330565A (en) | 2016-02-17 |
| CN105330565B true CN105330565B (en) | 2017-05-24 |
Family
ID=55281360
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510697605.5A Active CN105330565B (en) | 2015-10-23 | 2015-10-23 | Novel method for catalytically synthesizing cyanobenzene derivative through copper |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105330565B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108299335A (en) * | 2018-03-01 | 2018-07-20 | 天津力生制药股份有限公司 | A kind of synthetic method converting impurity 3- formoxyl Febustats to Febustat |
| CN113845442B (en) * | 2021-09-30 | 2023-09-29 | 孙国伟 | Method for preparing p-bromobenzonitrile |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3723463A (en) * | 1970-03-09 | 1973-03-27 | Squibb & Sons Inc | Dibenzooxazepines and dibenzothiazepines |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6114565A (en) * | 1999-09-03 | 2000-09-05 | Millennium Specialty Chemicals | Process for obtaining nitriles |
| US20100022589A1 (en) * | 2006-07-27 | 2010-01-28 | Mccoull William | Pyridine-3-carboxamide compounds and their use for inhibiting 11-beta-hydroxysteroid dehydrogenase |
-
2015
- 2015-10-23 CN CN201510697605.5A patent/CN105330565B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3723463A (en) * | 1970-03-09 | 1973-03-27 | Squibb & Sons Inc | Dibenzooxazepines and dibenzothiazepines |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105330565A (en) | 2016-02-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Gupta et al. | Counter ion effect in Au/Ag-catalyzed chemoselective 6-endo-dig N-and O-cyclizations of enyne–urea system: Diversity-oriented synthesis of annulated indoles | |
| Kanakaraju et al. | Ammonium acetate catalyzed an efficient one-pot three component synthesis of pyrano [3, 2-c] chromene derivatives | |
| CN104926811B (en) | The synthetic method of 3-cyanoimidazole also [1,2-a] pyridine compounds and application thereof | |
| Xu et al. | Pd-catalyzed tandem reaction of 2-aminostyryl nitriles with arylboronic acids: synthesis of 2-arylquinolines | |
| Prabhakara et al. | Ionic liquid-immobilized proline (s) organocatalyst-catalyzed one-pot multi-component Mannich reaction under solvent-free condition | |
| CN109232363B (en) | Synthetic method of 3-selenocyanoindole compound | |
| CN105330565B (en) | Novel method for catalytically synthesizing cyanobenzene derivative through copper | |
| CN110143918A (en) | - 2 (1H)-quinolinone activity skeleton of 3,4- dihydro -3- (2- (2-hydroxybenzoyl)) and synthetic method and application | |
| CN103420921A (en) | Method for synthesizing optically-active 2,3-dihydro quinazolinone derivative by using chiral spiro phosphoric acid as catalyst | |
| Chen et al. | Enantioselective Synthesis of Endocyclic β-Amino Acids with Two Contiguous Stereocenters via Hydrogenation of 3-Alkoxycarbonyl-2-Substituted Quinolines | |
| CN103113293A (en) | Polysubstituted quinoline derivative and preparation method thereof | |
| He et al. | Palladium-Catalyzed Desulfurative Hiyama Coupling of Thioureas to Achieve Amides via Selective C–N Bond Cleavage | |
| CN110317169B (en) | 1-substituted isoquinolone compound and preparation method thereof | |
| CN107573262B (en) | A kind of synthetic method of amidine compound | |
| KOUZNETSOV et al. | Synthesis of some secondary amine derivatives bearing a heteroaryl fragment | |
| Shit et al. | Regio-and Chemoselective Synthesis of 3-(Dihydrofuran-3 (2 H)-ylidene) isobenzofuran-1 (3 H)-imines via Tandem Alkynyl Prins-and Intramolecular Oxycyclization Reactions | |
| CN104974192B (en) | A kind of synthetic method of chiral phosphine ferrocene catalyst of thiophene-carboxamides substitution and application | |
| CN110590616B (en) | Sulfonyl hydrazone derivative and its preparing method and use | |
| Singh et al. | Regioselective synthesis of pyrrole and indole-fused isocoumarins catalysed by N^ ∧∧ O chelate ruthenium (II) complex | |
| CN102786466B (en) | Synthetic method of chiral Salan ligand | |
| CN102336763B (en) | Synthesis method for pyranocoumarin derivatives | |
| CN112745275B (en) | Synthetic method of 1,3, 4-oxadiazole heterocyclic compound | |
| CN104860881A (en) | Methods for synthesizing 8-(nitro methyl) quinoline compounds and 8-methylamino tetrahydroquinoline compounds | |
| CN111825509A (en) | Catalytic asymmetric synthesis method of chiral 3,4, 4-trisubstituted pyrrolidone compound | |
| CN113024475B (en) | Synthetic method of quinoxalinone compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20211220 Address after: 311100 room 407-2, 408, block D, building 1, No. 1378, Wenyi West Road, Cangqian street, Yuhang District, Hangzhou City, Zhejiang Province Patentee after: Hangzhou Shanghe Biomedical Technology Co.,Ltd. Patentee after: Zhejiang Kairui Biomedical Technology Co.,Ltd. Address before: No.58 Haishu Road, Cangqian street, Yuhang District, Hangzhou City, Zhejiang Province, 310036 Patentee before: Hangzhou Normal University |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A novel method for synthesizing benzonitrile derivatives catalyzed by copper Effective date of registration: 20220822 Granted publication date: 20170524 Pledgee: Hangzhou High-tech Financing Guarantee Co.,Ltd. Pledgor: Hangzhou Shanghe Biomedical Technology Co.,Ltd. Registration number: Y2022330001867 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20230626 Granted publication date: 20170524 Pledgee: Hangzhou High-tech Financing Guarantee Co.,Ltd. Pledgor: Hangzhou Shanghe Biomedical Technology Co.,Ltd. Registration number: Y2022330001867 |