CN108530377A - 1,2,4- oxadiazole analog derivative and preparation method thereof - Google Patents
1,2,4- oxadiazole analog derivative and preparation method thereof Download PDFInfo
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- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
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Abstract
The invention discloses a kind of 1,2,4 oxadiazole analog derivatives and preparation method thereof, and the preparation method includes：Amidoxim class compound, fragrant primary alconol, copper catalyst, alkali and organic solvent are mixed, it is heated that product A is obtained by the reaction；By product A dryings and isolate and purify to obtain 1,2,4 oxadiazole analog derivatives.Solve synthesize in the prior art 1,2,4 oxadiazole analog derivative compounds method and step it is complicated, of high cost, side reaction is more and yield is relatively low, meanwhile, environmental pollution is be easy to cause in building-up process, be not suitable for industrial scale production the problem of.
Description
Technical field
The present invention relates to organic synthesis fields, and in particular, to one kind 1,2,4- oxadiazoles analog derivative and its preparation side
Method.
Background technology
1,2,4- oxadiazole class compound is widely used and is curing because it has preferable biology and physiological activity
Medicine, fine chemistry industry, pesticide etc..The product for containing 1,2,4- oxadiazole structural units be widely used herbicide,
In the drugs such as the Pesticidal products such as insecticide, bactericidal agent and common anti-inflammatory, anticancer, antimalarial.Because it is answered field of medicaments is important
It is necessary to the research of its synthetic method with value.The method of synthesis 1,2,4- oxadiazole class compounds in the prior art
It is mainly the following：
(1) then bis- substitution -1,2,4- Evil bis- of 3,5- are synthesized with nitrile and azanol reaction under microwave condition with aldehyde reaction again
Azoles
This method has used microwave condition, though relatively simple industrial implementation is more difficult.
(2) nitrile and amidoxime are substrate using zinc chloride as catalyst, using DMF as solvent under conditions of p-methyl benzenesulfonic acid, 80
It is reacted at DEG C.
The substrate scope of application of the reaction is wider, there is higher yield.But the reaction has used p-methyl benzenesulfonic acid.
(3) 2013 years Kandre seminars develop that a kind of to use amidoxime and benzoyl cyanide be the life of substrate microwave method
The method of Cheng oxadiazoles.
The method of (four) 2015 peaks Nian Jianghuan seminar colors, successfully makes amidine hydrochloride complete at room temperature with methylarenes
At reaction.With Cu (OAc) 2 for catalyst, TBHP is oxidant, is reacted in DCE can be obtained target for 24 hours at room temperature for the reaction
Product.
Not only substrate applicability is extensive for this method, but also operation is simple, and raw material is cheap and easy to get, and reaction process is without dirt
Dye, thus it is suitble to large-scale industrial production.
(5) Kuram seminars proposed in 2016 using nitrile and amide as substrate, and it for catalyst O2 is oxidation to use CuI
Agent, the coupling of catalysis oxidation N-O keys, to realize that cyclization obtains target product.
This method has extensive substrate adaptability and functional group tolerance.
(6) 2016 years Baykov seminars report a synthesis being simple and efficient 3, the method for 5- bis- Qu Dai oxadiazoles,
The party is reacted 20min and can be obtained target product at room temperature using the super base combination of DMSO/KOH compositions.
The substrate scope of application of this method is also wide, and reaction condition is mild.
In conclusion there are many method that the prior art synthesizes 1,2,4- oxadiazole analog derivative compounds, but these sides
Some needs of method are by complicated synthesis step and side reaction is more and yield is relatively low；Some are using highly toxic substrate or have
Solvent easily causes environmental pollution；Some are catalyst using precious metal palladium etc., and cost costly, is not suitable for industrial production
The shortcomings of.Therefore it provides have very much must for a kind of novel green synthesis method of 1,2,4- oxadiazole analog derivative compounds of synthesis
It wants.
Invention content
The object of the present invention is to provide a kind of 1,2,4- oxadiazole analog derivatives and preparation method thereof, solve the prior art
The method and step of 1,2,4- oxadiazole analog derivative compounds of middle synthesis is complicated, of high cost, side reaction is more and yield is relatively low, together
When, the problem of be easy to causeing environmental pollution in building-up process, be not suitable for industrial scale production.
To achieve the goals above, described the present invention provides a kind of preparation method of 1,2,4- oxadiazole analog derivatives
Preparation method includes：
(1) amidoxim class compound, fragrant primary alconol, copper catalyst, alkali and organic solvent are mixed, it is heated to be obtained by the reaction
Product A；
(2) product A is dry and isolate and purify to obtain 1,2,4- oxadiazole analog derivatives.
The present invention also provides a kind of 1,2,4- oxadiazole analog derivatives, and described 1,2,4- oxadiazole analog derivatives are by above-mentioned
Preparation method be made.
Through the above technical solutions, the present invention provides a kind of 1,2,4- oxadiazole analog derivatives and preparation method thereof, institute
Stating preparation method includes：Amidoxim class compound, fragrant primary alconol, copper catalyst, alkali and organic solvent are mixed, heated reaction
Obtain product A；By product A dryings and isolate and purify to obtain 1,2,4- oxadiazole analog derivatives.Primary alconol fragrant first is in alkali and copper
Ketone is oxidized under catalyst action, then ketone is reacted with amidoxim generates five annulus compound intermediates, and then dioxygen oxidation
Intermediate generates 1,2,4- oxadiazole of target product.This method has following advantages compared with the existing technology：(1) in air environment
Middle progress, it is at low cost；(2) it without using noble metal, organic oxidizing agent, but is catalyzed using commercialization copper oxide or copper acetate
Agent, it is cost-effective；(3) raw material is easy to get, cheap；(4) synthetic method is efficient, and use scope is wide, is suitble to a variety of substrates
Reaction.
Other features and advantages of the present invention will be described in detail in subsequent specific embodiment part.
Description of the drawings
Attached drawing is to be used to provide further understanding of the present invention, an and part for constitution instruction, with following tool
Body embodiment is used to explain the present invention together, but is not construed as limiting the invention.In the accompanying drawings：
Fig. 1 is the reaction equation of amidoxim class compound and fragrant primary alconol in the present invention；
Fig. 2 is the hydrogen nuclear magnetic resonance spectrogram of -1,2,4 oxadiazole of 3,5 diphenyl prepared by embodiment 1；
Fig. 3 is the carbon-13 nmr spectra figure of -1,2,4 oxadiazole of 3,5 diphenyl prepared by embodiment 1；
Fig. 4 is the hydrogen nuclear magnetic resonance spectrogram of-3-phenyl-1,2,4- oxadiazoles of 5- (3- bromophenyls) prepared by embodiment 2；
Fig. 5 is the carbon-13 nmr spectra figure of-3-phenyl-1,2,4- oxadiazoles of 5- (3- bromophenyls) prepared by embodiment 2；
Fig. 6 is the hydrogen nuclear magnetic resonance spectrogram of-3-- 1,2,4-oxadiazoles of phenyl of 5- (2- aminomethyl phenyls) prepared by embodiment 3；
Fig. 7 is the carbon-13 nmr spectra figure of-3-- 1,2,4-oxadiazoles of phenyl of 5- (2- aminomethyl phenyls) prepared by embodiment 3；
Fig. 8 is the hydrogen nuclear magnetic resonance spectrogram of 5- (2- chlorphenyls)-3--1,2,4-oxadiazoles of phenyl prepared by embodiment 4；
Fig. 9 is the carbon-13 nmr spectra figure of 5- (2- chlorphenyls)-3--1,2,4-oxadiazoles of phenyl prepared by embodiment 4；
Figure 10 is the nuclear magnetic resonance of 5- (3.5- Dimethoxyphenyls)-3--1,2,4-oxadiazoles of phenyl prepared by embodiment 5
Hydrogen spectrogram；
Figure 11 is the nuclear magnetic resonance of 5- (3.5- Dimethoxyphenyls)-3--1,2,4-oxadiazoles of phenyl prepared by embodiment 5
Carbon spectrogram；
Figure 12 is the hydrogen nuclear magnetic resonance spectrogram of 5- (4- bromophenyls)-3--1,2,4-oxadiazoles of phenyl prepared by embodiment 6；
Figure 13 is the carbon-13 nmr spectra figure of 5- (4- bromophenyls)-3--1,2,4-oxadiazoles of phenyl prepared by embodiment 6；
Figure 14 is the nuclear-magnetism of 5- (2,4 dichloro benzene base)-3- (4- aminomethyl phenyls)-1,2,4-oxadiazoles prepared by embodiment 7
Resonate hydrogen spectrogram；
Figure 15 is the nuclear-magnetism of 5- (2,4 dichloro benzene base)-3- (4- aminomethyl phenyls)-1,2,4-oxadiazoles prepared by embodiment 7
Resonate carbon spectrogram；
Figure 16 is the nuclear magnetic resonance spectroscopy of 5- phenyl-3- (4- aminomethyl phenyls)-1,2,4-oxadiazoles prepared by embodiment 8
Figure；
Figure 17 is the carbon-13 nmr spectra of 5- phenyl-3- (4- aminomethyl phenyls)-1,2,4-oxadiazoles prepared by embodiment 8
Figure.
Figure 18 is the nuclear magnetic resonance of 5- (4- bromophenyls)-3- (4- aminomethyl phenyls)-1,2,4-oxadiazoles prepared by embodiment 9
Hydrogen spectrogram；
Figure 19 is-the 1,2,4-of 5- (4- bromophenyls)-3- (4- aminomethyl phenyls)-1,2,4-oxadiazoles prepared by embodiment 9
The carbon-13 nmr spectra figure of oxadiazole.
Reference sign
In Fig. 1, R1For H, 4-CH3, 4-Cl or 4-Br；R2For H, 2-CH3、2-Cl、3-Br、4-CH3, 4-Br, 2,4-
Cl2Or 3,5- (OCH3)2。
Specific implementation mode
The specific implementation mode of the present invention is described in detail below.It should be understood that described herein specific
Embodiment is merely to illustrate and explain the present invention, and is not intended to restrict the invention.
The endpoint of disclosed range and any value are not limited to the accurate range or value herein, these ranges or
Value should be understood as comprising the value close to these ranges or value.For numberical range, between the endpoint value of each range, respectively
It can be combined with each other between the endpoint value of a range and individual point value, and individually between point value and obtain one or more
New numberical range, these numberical ranges should be considered as specific open herein.
The present invention provides a kind of preparation method of 1,2,4- oxadiazole analog derivatives, the preparation method includes：
(1) amidoxim class compound, fragrant primary alconol, copper catalyst, alkali and organic solvent are mixed, it is heated to be obtained by the reaction
Product A；
(2) product A is dry and isolate and purify to obtain 1,2,4- oxadiazole analog derivatives.
In a kind of preferred embodiment of the present invention, in order to enable reaction is smoothed out, yield is further increased, together with
Amine oxime compound, fragrant primary alconol, copper catalyst and alkali are 1 according to molar ratio:1.5-2:0.1-0.2:The ratio of 0.8-1 carries out
Mixing.
In a kind of preferred embodiment of the present invention, in order to enable reaction is smoothed out, yield is further increased, together with
The structural formula of amine oxime compound is
Wherein, R1For H, 4-CH3, 4-Cl or 4-Br.
In a kind of preferred embodiment of the present invention, in order to enable reaction is smoothed out, yield is further increased, virtue
The structural formula of fragrant primary alconol is
Wherein, R2For H, 2-CH3、2-Cl、3-Br、4-CH3, 4-Br, 2,4-Cl2Or 3,5- (OCH3)2。
In a kind of preferred embodiment of the present invention, in order to enable reaction is smoothed out, yield, copper are further increased
Catalyst is selected from copper oxide and/or copper acetate.
In a kind of preferred embodiment of the present invention, in order to enable reaction is smoothed out, yield, alkali are further increased
It is one or more in potassium carbonate, potassium hydroxide, sodium ethoxide and in cesium carbonate.
In a kind of preferred embodiment of the present invention, in order to enable reaction is smoothed out, yield is further increased, is had
Solvent is toluene and/or dimethyl sulfoxide (DMSO).
In a kind of preferred embodiment of the present invention, in order to enable reaction is smoothed out, yield is further increased, is added
The condition of thermal response includes：Temperature is 110-120 DEG C, time 22-26h.
In a kind of preferred embodiment of the present invention, in order to enable reaction is smoothed out, yield is further increased,
In step (2), the preparation method further includes：Product A is extracted with ethyl acetate, is done later with anhydrous sodium sulfate
It is dry, crude product is obtained after reduced pressure, and 1,2,4- oxadiazole analog derivatives are obtained after obtained crude by column chromatography is detached；
Preferably, in column chromatography for separation, solvent is made of petroleum ether and ethyl acetate, and petroleum ether and ethyl acetate
Volume ratio be 5：0.8-1.2.
The present invention also provides a kind of 1,2,4- oxadiazole analog derivatives, and described 1,2,4- oxadiazole analog derivatives are by above-mentioned
Preparation method be made；
Preferably, the structural formula of 1,2,4- oxadiazole analog derivatives is：
Wherein, R1Selected from H, 4-CH3, 4-Cl or 4-Br；R2For H, 2-CH3、2-
Cl、3-Br、4-CH3, 4-Br, 2,4-Cl2Or 3,5- (OCH3)2。
The present invention will be described in detail by way of examples below.
Embodiment 1
It takes 0.5mmol benzoyl amidoximes, 1.0mmol benzyl alcohols to be placed in reaction tube, subsequently sequentially adds 0.05mmol
CuO、0.5mmol C2H5ONa, 3mL toluene are stirred to react for 24 hours at 110 DEG C.Product is extracted with ethyl acetate, it is anhydrous
Sodium sulphate is dried, and is concentrated under reduced pressure, is obtained crude product, and by crude product purified by silica gel column chromatography, (solvent volume ratio is petroleum ether：Ethyl acetate
=20：1) white solid, i.e., 3 are purified to obtain, 5 diphenyl -1,2,4 oxadiazoles, yield 74%, fusing point is 105-106 DEG C；
Its nuclear-magnetism characterize data is：
1H NMR(300MHz,CDCl3)δ8.19-8.13(m,4H),7.56-7.46(m,6H)；Its hydrogen nuclear magnetic resonance spectrogram
See Fig. 2.
13C NMR(125MHz,CDCl3)δ176.1,169.4,133.1,133.6,129.5,129.2,128.6,127.9,
127.4,124.7；Its carbon-13 nmr spectra figure is shown in Fig. 3.
Embodiment 2
0.5mmol benzoyl amidoximes, 1.0mmol 3- bromobenzene methanol is taken to be placed in reaction tube, subsequently sequentially add
0.05mmol CuO, 0.5mmol NaOH, 3mL toluene, are stirred to react for 24 hours at 110 DEG C.Product is extracted with ethyl acetate
It takes, anhydrous sodium sulfate drying is concentrated under reduced pressure, obtains crude product, and by crude product purified by silica gel column chromatography, (solvent volume ratio is petroleum ether：
Ethyl acetate=20：1) white solid, i.e. 5- (3- bromophenyls)-3-phenyl-1,2,4- oxadiazoles are purified to obtain.Yield 44% melts
102-104 DEG C of point；
Its nuclear-magnetism characterize data is：
1H NMR(300MHz,CDCl3) δ 8.33 (s, 1H), 8.12-8.08 (m, 3H), 7.69 (d, J=7.8Hz, 1H),
7.48-7.36(m,4H)；Its hydrogen nuclear magnetic resonance spectrogram is shown in Fig. 4.
13C NMR(125MHz,CDCl3)δ174.7,169.4,136.1,131.8,131.4,131.1,129.3,127.9,
127.1,127.0,126.5,123.6；Its carbon-13 nmr spectra figure is shown in Fig. 5.
Embodiment 3
0.5mmol benzoyl amidoximes, 1.2mmol 2- methylbenzyl alcohols is taken to be placed in reaction tube, subsequently sequentially add
0.05mmol CuO、0.5mmol K2CO3, 3mL toluene, be stirred to react at 120 DEG C for 24 hours, product extracted with ethyl acetate
It takes, anhydrous sodium sulfate drying is concentrated under reduced pressure, obtains crude product, and by crude product purified by silica gel column chromatography, (solvent volume ratio is petroleum ether：
Ethyl acetate=20：1) white solid, i.e. 5- (2- aminomethyl phenyls)-3-phenyl-1,2,4-oxadiazoles are purified to obtain.Yield 34%,
50-52 DEG C of fusing point；
Its nuclear-magnetism characterize data is：
1H NMR(300MHz,CDCl3)δ8.15-8.10(m,3H),7.48-7.40(m,4H),7.34-7.29(m,2H),
2.74(s,3H)；Its hydrogen nuclear magnetic resonance spectrogram is shown in Fig. 6.
13C NMR(125MHz,CDCl3)δ176.8,169.0,139.6,132.6,132.3,131.5,130.6,129.2,
127.9,127.5,126.7,123.9,22.4；Its carbon-13 nmr spectra figure is shown in Fig. 7.
Embodiment 4
0.4mmol benzoyl amidoximes, 0.72mmol 2- chlorobenzene methanols is taken to be placed in reaction tube, subsequently sequentially add
0.06mmol CuO、0.4mmol CsCO3, 3mL toluene, be stirred to react for 24 hours at 110 DEG C；Product is carried out with ethyl acetate
Extraction, anhydrous sodium sulfate drying, is concentrated under reduced pressure, obtains crude product, and by crude product purified by silica gel column chromatography, (solvent volume ratio is oil
Ether：Ethyl acetate=20：1) white solid, i.e. 5- (2- chlorphenyls)-3- phenyl-1,2,4-oxadiazoles are purified to obtain.Yield 61%,
56-57 DEG C of fusing point；
Its nuclear-magnetism characterize data is：
1H NMR(300MHz,CDCl3)δ8.15-8.09(m,3H),7.55-7.37(m,6H)；Its hydrogen nuclear magnetic resonance spectrogram
See Fig. 8.
13C NMR(125MHz,CDCl3)δ174.7,169.1,134.3,133.5,132.3,131.8,131.7,129.3,
128.0,127.5,127.2,124.1；Its carbon-13 nmr spectra figure is shown in Fig. 9.
Embodiment 5
0.8mmol benzoyl amidoximes, 1.6mmol 2,4- 3,5-dimethoxybenzoic alcohols is taken to be placed in reaction tube, subsequently successively
0.12mmol CuO, 0.8mmol KOH, 2.5mL toluene is added, 26h is stirred to react at 120 DEG C, by product ethyl acetate
It is extracted, anhydrous sodium sulfate drying is concentrated under reduced pressure, obtains crude product, and by crude product purified by silica gel column chromatography, (solvent volume ratio is stone
Oily ether：Ethyl acetate=20：1) white solid, i.e. 5- (3.5- Dimethoxyphenyls)-3- phenyl-1,2,4-Evil two are purified to obtain
Azoles.Yield 56%, 116-117 DEG C of fusing point；
Its nuclear-magnetism characterize data is：
1H NMR(300MHz,CDCl3) δ 8.13 (d, J=3.9Hz, 2H), 7.46 (d, J=Hz, 3H), 7.31 (d, J=
1.5Hz,2H)6.63(s,1H),3.84(s,6H)；Its hydrogen nuclear magnetic resonance spectrogram is shown in Figure 10.
13C NMR(125MHz,CDCl3)δ176.0,169.4,161.6,131.6,129.2,127.9,127.3,126.2,
106.2,105.9,56.1；Its carbon-13 nmr spectra figure is shown in Figure 11.
Embodiment 6
0.5mmol benzoyl amidoximes, 1.0mmol 4- bromobenzene methanol is taken to be placed in reaction tube, subsequently sequentially add
0.05mmol CuO、0.4mmol C2H5ONa, 3mL toluene are stirred to react 22h at 110 DEG C, and product is carried out with ethyl acetate
Extraction, anhydrous sodium sulfate drying, is concentrated under reduced pressure, obtains crude product, and by crude product purified by silica gel column chromatography, (solvent volume ratio is oil
Ether：Ethyl acetate=20：1) white solid, i.e. 5- (4- bromophenyls)-3- phenyl-1,2,4-oxadiazoles are purified to obtain.Yield 68%,
114-118 DEG C of fusing point；
Its nuclear-magnetism characterize data is：
1H NMR(300MHz,CDCl3)δ8.12-8.00(m,4H),7.67-7.62(m,2H),7.48-7.45(m,3H)；
Its hydrogen nuclear magnetic resonance spectrogram is shown in Figure 12.
13C NMR(125MHz,CDCl3)δ175.3,169.5,132.9,131.7,130.0 129.3,128.2,127.9,
127.1,123.6；Its carbon-13 nmr spectra figure is shown in Figure 13.
Embodiment 7
0.5mmol 4- toluyl amidoximes, 1.0mmol 2,4-DCBAs is taken to be placed in reaction tube, subsequently
Sequentially add 0.05mmol Cu (OAc)2、0.5mmol C2H5ONa, 2.5mL DMSO are stirred to react for 24 hours at 110 DEG C, will produce
Object is extracted with ethyl acetate, and anhydrous sodium sulfate drying is concentrated under reduced pressure, obtains crude product, and crude product purified by silica gel column chromatography is (molten
Agent volume ratio is petroleum ether：Ethyl acetate=20：1) white solid, i.e. 5- (2,4- dichlorophenyl) -3- (4- methylbenzenes are purified to obtain
Base)-1,2,4-oxadiazoles.Yield 56%, 82-85 DEG C of fusing point；
Its nuclear-magnetism characterize data is：
1H NMR(300MHz,CDCl3)δ8.12-7.99(m,3H),7.56-7.25(m,4H)；Its hydrogen nuclear magnetic resonance spectrogram
See Figure 14.
13C NMR(125MHz,CDCl3)δ173.7,169.2,142.2,139.3,135.1,133.1,131.8,130.0,
128.0,127.9,124.1,122.6,22.0；Its carbon-13 nmr spectra figure is shown in Figure 15.
Embodiment 8
0.5mmol 4- toluyl amidoximes, 1.0mmol benzyl alcohols is taken to be placed in reaction tube, subsequently sequentially add
0.05mmol CuO、0.5mmol C2H5ONa, 2.5mL toluene, be stirred to react at 110 DEG C for 24 hours, by product ethyl acetate into
Row extraction, anhydrous sodium sulfate drying, is concentrated under reduced pressure, obtains crude product, and by crude product purified by silica gel column chromatography, (solvent volume ratio is oil
Ether：Ethyl acetate=20：1) white solid, i.e. 5- phenyl-3- (4- aminomethyl phenyls)-1,2,4-oxadiazoles are purified to obtain.Yield
48%, 104-106 DEG C of fusing point；
Its nuclear-magnetism characterize data is：
1H NMR(300MHz,CDCl3) δ 8.17 (d, J=6.9Hz, 2H), 8.01 (d, J=7.5Hz, 2H), 7.55-7.49
(m, 3H), 7.26 (d, J=Hz, 2H), 2.38 (s, 1H)；Its hydrogen nuclear magnetic resonance spectrogram is shown in Figure 16.
13C NMR(125MHz,CDCl3)δ1759,169.4,141.9,133.1,130.0,129.5,128.6,127.9,
124.8,124.6,22.0；Its carbon-13 nmr spectra figure is shown in Figure 17.
Embodiment 9
0.5mmol 4- toluyl amidoximes, 1.0mmol 4- bromobenzene methanol is taken to be placed in reaction tube, subsequently successively
0.05mmol Cu (OAc) are added2、0.5mmol C2H5ONa, 2.5mL toluene are stirred to react for 24 hours at 110 DEG C, product are used
Ethyl acetate is extracted, and anhydrous sodium sulfate drying is concentrated under reduced pressure, crude product is obtained, by crude product purified by silica gel column chromatography (solvent body
Product is than being petroleum ether：Ethyl acetate=20：1) purify to obtain white solid, i.e. 5- (4- bromophenyls) -3- (4- aminomethyl phenyls) -1,2,
4-oxadiazoles.Yield 40%, 123-128 DEG C of fusing point；
Its nuclear-magnetism characterize data is：
1H NMR(300MHz,CDCl3)1H NMR(300MHz,CDCl3) δ 8.03-7.97 (m, 4H), 7.63 (d, J=
8.4Hz, 2H), 7.26 (d, J=7.8Hz, 2H), 2.37 (s, 3H)；Its hydrogen nuclear magnetic resonance spectrogram is shown in Figure 18.
13C NMR(125MHz,CDCl3)δ175.1,169.4,142.0,132.8,130.0,129.9,128.0,127.8,
124.3,123.6,22.0. its carbon-13 nmr spectra figure is shown in Figure 19.
The preferred embodiment of the present invention has been described above in detail, still, during present invention is not limited to the embodiments described above
Detail can carry out a variety of simple variants to technical scheme of the present invention within the scope of the technical concept of the present invention, this
A little simple variants all belong to the scope of protection of the present invention.
It is further to note that specific technical features described in the above specific embodiments, in not lance
In the case of shield, can be combined by any suitable means, in order to avoid unnecessary repetition, the present invention to it is various can
The combination of energy no longer separately illustrates.
In addition, various embodiments of the present invention can be combined randomly, as long as it is without prejudice to originally
The thought of invention, it should also be regarded as the disclosure of the present invention.
Claims (10)
1. one kind 1,2, the preparation method of 4- oxadiazole analog derivatives, which is characterized in that the preparation method includes：
(1) amidoxim class compound, fragrant primary alconol, copper catalyst, alkali and organic solvent are mixed, it is heated that product is obtained by the reaction
A；
(2) product A is dry and isolate and purify to obtain 1,2,4- oxadiazole analog derivatives.
2. preparation method according to claim 1, wherein amidoxim class compound, fragrant primary alconol, copper catalyst and alkali are pressed
It is 1 according to molar ratio:1.5-2:0.1-0.2:The ratio of 0.8-1 is mixed.
3. preparation method according to claim 1, wherein the structural formula of amidoxim class compound is
Wherein, R1For H, 4-CH3, 4-Cl or 4-Br.
4. preparation method according to claim 1, wherein the structural formula of fragrant primary alconol is
Wherein, R2For H, 2-CH3、2-Cl、3-Br、4-CH3, 4-Br, 2,4-Cl2Or 3,5- (OCH3)2。
5. preparation method according to claim 1, wherein copper catalyst is selected from copper oxide and/or copper acetate.
6. preparation method according to claim 1, wherein alkali is in potassium carbonate, potassium hydroxide, sodium ethoxide and cesium carbonate
It is one or more.
7. preparation method according to claim 1, wherein organic solvent is toluene and/or dimethyl sulfoxide (DMSO).
8. preparation method according to claim 1, wherein the condition for heating reaction includes：Temperature is 110-120 DEG C, when
Between be 22-26h.
9. preparation method according to claim 1, wherein in step (2), the preparation method further includes：By product A
It is extracted with ethyl acetate, is dried later with anhydrous sodium sulfate, crude product is obtained after reduced pressure, the thick production that will be obtained
Object obtains 1,2,4- oxadiazole analog derivatives after column chromatography for separation；
Preferably, in column chromatography for separation, solvent is made of petroleum ether and ethyl acetate, and the body of petroleum ether and ethyl acetate
Product is than being 20：0.8-1.2.
10. one kind 1,2,4- oxadiazole analog derivatives, which is characterized in that described 1,2,4- oxadiazole analog derivatives are by claim
Preparation method described in any one of 1-9 is made；
Preferably, the structural formula of 1,2,4- oxadiazole analog derivatives is：
Wherein, R1Selected from H, 4-CH3, 4-Cl or 4-Br；R2For H, 2-CH3、2-Cl、3-
Br、4-CH3, 4-Br, 2,4-Cl2Or 3,5- (OCH3)2。
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| CN110372626A (en) * | 2019-07-19 | 2019-10-25 | 河南大学 | A method of preparing 1,2,4- furodiazole compound |
| CN114874154A (en) * | 2022-06-16 | 2022-08-09 | 北京理工大学 | 3,3 '-disubstituted-5, 5' -bis (1,2, 4-oxadiazole) compound and preparation method thereof |
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| CN114874154A (en) * | 2022-06-16 | 2022-08-09 | 北京理工大学 | 3,3 '-disubstituted-5, 5' -bis (1,2, 4-oxadiazole) compound and preparation method thereof |
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