CN108084109A - Synthesis method of 2, 5-disubstituted-1, 3, 4-oxadiazole - Google Patents
Synthesis method of 2, 5-disubstituted-1, 3, 4-oxadiazole Download PDFInfo
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- CN108084109A CN108084109A CN201711440986.4A CN201711440986A CN108084109A CN 108084109 A CN108084109 A CN 108084109A CN 201711440986 A CN201711440986 A CN 201711440986A CN 108084109 A CN108084109 A CN 108084109A
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- -1 2, 5-disubstituted-1, 3, 4-oxadiazole Chemical class 0.000 title abstract description 12
- 238000001308 synthesis method Methods 0.000 title 1
- 238000006243 chemical reaction Methods 0.000 claims abstract description 60
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims abstract description 49
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 38
- 239000003054 catalyst Substances 0.000 claims abstract description 34
- 229910000027 potassium carbonate Inorganic materials 0.000 claims abstract description 24
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 20
- 239000002904 solvent Substances 0.000 claims abstract description 15
- 239000000654 additive Substances 0.000 claims abstract description 11
- 230000000996 additive effect Effects 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- 239000003814 drug Substances 0.000 claims abstract description 3
- 238000005580 one pot reaction Methods 0.000 claims abstract 2
- 230000001699 photocatalysis Effects 0.000 claims abstract 2
- 238000007146 photocatalysis Methods 0.000 claims abstract 2
- 235000019441 ethanol Nutrition 0.000 claims description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- 238000003786 synthesis reaction Methods 0.000 claims description 7
- VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 claims description 2
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- WHLUQAYNVOGZST-UHFFFAOYSA-N tifenamil Chemical group C=1C=CC=CC=1C(C(=O)SCCN(CC)CC)C1=CC=CC=C1 WHLUQAYNVOGZST-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 21
- 229940079593 drug Drugs 0.000 abstract description 2
- 238000010189 synthetic method Methods 0.000 abstract description 2
- 238000004440 column chromatography Methods 0.000 description 16
- 238000000746 purification Methods 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
- 239000005456 alcohol based solvent Substances 0.000 description 13
- WARCRYXKINZHGQ-UHFFFAOYSA-N benzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1 WARCRYXKINZHGQ-UHFFFAOYSA-N 0.000 description 9
- 238000006555 catalytic reaction Methods 0.000 description 6
- DCJKUXYSYJBBRD-UHFFFAOYSA-N 2,5-diphenyl-1,3,4-oxadiazole Chemical class C1=CC=CC=C1C1=NN=C(C=2C=CC=CC=2)O1 DCJKUXYSYJBBRD-UHFFFAOYSA-N 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 4
- 230000003760 hair shine Effects 0.000 description 4
- 150000002429 hydrazines Chemical class 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- OHWQVYVPAAGBHW-UHFFFAOYSA-N 2,5-bis(3-methylphenyl)-1,3,4-oxadiazole Chemical compound CC1=CC=CC(C=2OC(=NN=2)C=2C=C(C)C=CC=2)=C1 OHWQVYVPAAGBHW-UHFFFAOYSA-N 0.000 description 1
- ASDRGEKUFQCMBN-UHFFFAOYSA-N 2,5-bis(4-methoxyphenyl)-1,3,4-oxadiazole Chemical compound C1=CC(OC)=CC=C1C1=NN=C(C=2C=CC(OC)=CC=2)O1 ASDRGEKUFQCMBN-UHFFFAOYSA-N 0.000 description 1
- XYCVDMCFWPHYNZ-UHFFFAOYSA-N 2,5-bis(4-methylphenyl)-1,3,4-oxadiazole Chemical compound C1=CC(C)=CC=C1C1=NN=C(C=2C=CC(C)=CC=2)O1 XYCVDMCFWPHYNZ-UHFFFAOYSA-N 0.000 description 1
- ZMFUDRWYDBQWEZ-UHFFFAOYSA-N 2,5-bis(4-tert-butylphenyl)-1,3,4-oxadiazole Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=NN=C(C=2C=CC(=CC=2)C(C)(C)C)O1 ZMFUDRWYDBQWEZ-UHFFFAOYSA-N 0.000 description 1
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 1
- UYIMBYKIIMYFPS-UHFFFAOYSA-N 4-bromobenzohydrazide Chemical compound NNC(=O)C1=CC=C(Br)C=C1 UYIMBYKIIMYFPS-UHFFFAOYSA-N 0.000 description 1
- PKBGHORNUFQAAW-UHFFFAOYSA-N 4-chlorobenzohydrazide Chemical compound NNC(=O)C1=CC=C(Cl)C=C1 PKBGHORNUFQAAW-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000012048 reactive intermediate Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- 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
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The invention discloses a synthetic method of a drug intermediate 2, 5-disubstituted-1, 3, 4-oxadiazole. The invention takes simple hydrazide compounds as raw materials to synthesize the 2, 5-disubstituted-1, 3, 4-oxadiazole by a one-pot method under the photocatalysis. The common halogen lamp is used as a light source, eosinY is used as a catalyst, potassium carbonate is used as an additive, ethanol is used as a solvent, and the reaction can be carried out at room temperature to generate the 2, 5-disubstituted-1, 3, 4-oxadiazole. The invention has the characteristics of simple raw material source, mild reaction condition and the like.
Description
Technical field
The invention belongs to symmetrical 2,5- bis- to substitute -1.3.4- oxadiazoles and its derivative preparing technical field.It is specifically related to
One kind is in ethanol solution, using potassium carbonate as alkali, dye class catalyst eosin Y catalysis hydrazide kind compounds generation symmetrical 2,
5- bis- substitutes the method for -1.3.4- oxadiazoles and its derivative.
Background technology
Heterocycle 1.3.4- oxadiazoles are a kind of very big reactive intermediates of application value of field of fine chemical, in many drugs
It can be found in the molecular structure of chemistry.
EosinY belongs to dye class catalyst, and due to it efficiently, inexpensively, it is a large amount of that the features such as dosage is few causes catalytic field
Research boom.
Many synthesis 2,5- bis- disclosed in recent years substitute the method for -1.3.4- oxadiazoles.Mainly make multi-component anti-
More complicated raw material should or be used, what is had will use transition-metal catalysis, and the reaction time is longer, and condition is harsh.
Catalyst is made using common eosinY in this article, realize under room temperature and air conditions can catalytic reaction carry out, have
Easy to operate, mild condition is swift in response, high conversion rate and the advantages that high income.
The content of the invention
It is an object of the invention to provide a kind of operating condition is simple, reaction condition is mild, high selectivity, the system of high income
The method of standby cinnamic acid ester derivant.Compared with the method in the prior art, this system maximum feature is to use catalytic amount
Catalyst, easy to operate, raw material is easy to get, it is small to pollute, safety is cheap and environmentally protective.
For the present invention using common dyestuff catalyst eosinY as catalyst, hydrazide kind compound is reaction substrate, reaction temperature
Spend for room temperature, the reaction time for 12 it is small when or so, efficient catalytic prepares symmetrical 2,5- bis- and substitutes -1.3.4- Evil in ethyl alcohol phase
Diazole and its derivative.Wherein, hydrazide kind compound used include to methyl, to methoxyl group, to tertiary butyl, to chlorine, to bromine
Benzoyl hydrazine and heterocyclic thiophene hydrazides.
The specific reaction equation such as chemical equation (1) of the present invention：
Wherein R is (1) containing methyl, methoxyl group, the phenyl ring of the substituent groups such as tertiary butyl, halogen (fluorine, chlorine).
(2) thiophene heterocycle.
The preferred reaction step of the present invention is as follows：The benzoyl hydrazine of 0.5mmol is added in the reaction tube of 10ml
Then the potassium carbonate 0.138g of photochemical catalyst the eosinY 0.010g and 1mmol of 0.068g, 3mol% add in 2ml solvents, use
Light intensity 0.4W/cm2Reaction is stirred at room temperature with fan control in halogen light irradiation.React 12 it is small when after, in reaction solution use column chromatography
Methods For Purification product.
The catalyst eosinY dosages can be 2mol%, 3mol%, 5mol%.
The additive basic can be potassium carbonate (K2CO3), potassium phosphate (K3PO4), sodium phosphate (Na3PO4), triethylamine
(Et3N)。
Solvent used has ethyl alcohol, methanol, isopropanol, tetrahydrofuran in this reaction, and wherein ethyl alcohol effect is best.
The present invention relates to compound it is specific as follows：
The present invention has the following advantages：In the reaction using under single reaction raw material, the catalyst of catalytic amount, illumination condition
Room temperature is with regard to that can smoothly complete.
Description of the drawings
The simple main reactant (hydrazide kind compound) for illustrating the reaction of attached drawing 1 and product (2,5- bis- substitute-
1.3.4- oxadiazole).
Attached drawing 2 is shown as the H spectrum spectrograms of compound 1-1.
Specific embodiment
It lifts specific embodiment again below to be further described the present invention, single present disclosure is not limited thereto.
Embodiment 1：Use the preparation of eosinY catalysis 2, the 5- diphenyl -1.3.4- oxadiazoles of 2mol%.
The photochemical catalyst eosinY of the benzoyl hydrazine 0.068g 2mol% of 0.5mmol is added in the reaction tube of 10ml
Then the potassium carbonate 0.138g of 0.007g and 1mmol adds in 2ml alcohol solvents, with light intensity 0.4W/cm2Halogen light irradiation is used
Reaction is stirred at room temperature in fan control.React 12 it is small when after, in reaction solution use column chromatography Methods For Purification product.Yield is
29%.
Embodiment 2：Use the preparation of eosinY catalysis 2, the 5- diphenyl -1.3.4- oxadiazoles of 3mol%.
The photochemical catalyst eosinY of the benzoyl hydrazine 0.068g, 3mol% of 0.5mmol are added in the reaction tube of 10ml
Then the potassium carbonate 0.138g of 0.010g and 1mmol adds in 2ml alcohol solvents, with light intensity 0.4W/cm2Halogen light irradiation is used
Reaction is stirred at room temperature in fan control.React 12 it is small when after, in reaction solution use column chromatography Methods For Purification product.Yield is
68%.
Embodiment 3：Use the preparation of eosinY catalysis 2, the 5- diphenyl -1.3.4- oxadiazoles of 5mol%.
The photochemical catalyst eosinY of the benzoyl hydrazine 0.068g, 5mol% of 0.5mmol are added in the reaction tube of 10ml
Then the potassium carbonate 0.138g of 0.017g and 1mmol adds in 2ml alcohol solvents, with light intensity 0.4W/cm2Halogen light irradiation is used
Reaction is stirred at room temperature in fan control.React 12 it is small when after, in reaction solution use column chromatography Methods For Purification product.Yield is
68%.
Embodiment 4：Potassium phosphate (K3PO4) it is used for the preparation of 2,5- diphenyl -1.3.4- oxadiazoles.
The photochemical catalyst eosinY of the benzoyl hydrazine 0.068g, 3mol% of 0.5mmol are added in the reaction tube of 10ml
Then the potassium phosphate 0.212g of 0.010g and 1mmol adds in 2ml alcohol solvents, with light intensity 0.4W/cm2Halogen light irradiation is used
Reaction is stirred at room temperature in fan control.React 12 it is small when after, in reaction solution use column chromatography Methods For Purification product.Yield is
42%.
Embodiment 5：Sodium phosphate (Na3PO4) it is used for the preparation of 2,5- diphenyl -1.3.4- oxadiazoles.
The photochemical catalyst eosinY of the benzoyl hydrazine 0.068g, 3mol% of 0.5mmol are added in the reaction tube of 10ml
Then the sodium phosphate 0.164g of 0.010g and 1mmol adds in 2ml alcohol solvents, with light intensity 0.4W/cm2Halogen light irradiation is used
Reaction is stirred at room temperature in fan control.React 12 it is small when after, in reaction solution use column chromatography Methods For Purification product.Yield is
39%.
Embodiment 6：Triethylamine (Et3N) it is used for the preparation of 2,5- diphenyl -1.3.4- oxadiazoles.
The photochemical catalyst eosinY of the benzoyl hydrazine 0.068g, 3mol% of 0.5mmol are added in the reaction tube of 10ml
Then the triethylamine 0.101g of 0.010g and 1mmol adds in 2ml alcohol solvents, with light intensity 0.4W/cm2Halogen light irradiation is used
Reaction is stirred at room temperature in fan control.React 12 it is small when after, in reaction solution use column chromatography Methods For Purification product.Yield is
29%.
Embodiment 7：Methanol as solvent is used for the preparation of 2,5- diphenyl -1.3.4- oxadiazoles.
The photochemical catalyst eosinY of the benzoyl hydrazine 0.068g, 3mol% of 0.5mmol are added in the reaction tube of 10ml
Then the potassium carbonate 0.138g of 0.010g and 1mmol adds in 2ml methanol solvates, with light intensity 0.4W/cm2Halogen light irradiation is used
Reaction is stirred at room temperature in fan control.React 12 it is small when after, in reaction solution use column chromatography Methods For Purification product.Yield is
55%.
Embodiment 8：Isopropanol makees preparation of the solvent for 2,5- diphenyl -1.3.4- oxadiazoles.
The photochemical catalyst eosinY of the benzoyl hydrazine 0.068g, 3mol% of 0.5mmol are added in the reaction tube of 10ml
Then the potassium carbonate 0.138g of 0.010g and 1mmol adds in 2ml isopropanol solvents, with light intensity 0.4W/cm2Halogen light irradiation,
Reaction is stirred at room temperature with fan control.React 12 it is small when after, in reaction solution use column chromatography Methods For Purification product.Yield is
62%.
Embodiment 9：Using the eosinY catalyst of 3mol%, potassium carbonate makees additive, and ethanol as solvent is used for 2,5-
Bis (3-methylphenyl) -1,3,4-oxadiazole preparation.
The photochemical catalyst of 3- methyl-benzoyl the hydrazines 0.075g, 3mol% of 0.5mmol are added in the reaction tube of 10ml
Then the potassium carbonate 0.138g of eosinY 0.010g and 1mmol add in 2ml alcohol solvents, with light intensity 0.4W/cm2Halogen lamp shines
It penetrates, reaction is stirred at room temperature with fan control.React 12 it is small when after, in reaction solution use column chromatography Methods For Purification product.Yield
For 53%.
Embodiment 10：The eosinY catalyst of 3mol%, potassium carbonate make additive, and ethanol as solvent is used for 2,5-bis
(4-methylphenyl) -1,3,4-oxadiazole preparation.
The photochemical catalyst of 4- methyl-benzoyl the hydrazines 0.075g, 3mol% of 0.5mmol are added in the reaction tube of 10ml
Then the potassium carbonate 0.138g of eosinY 0.010g and 1mmol add in 2ml alcohol solvents, with light intensity 0.4W/cm2Halogen lamp shines
It penetrates, reaction is stirred at room temperature with fan control.React 12 it is small when after, in reaction solution use column chromatography Methods For Purification product.Yield
For 70%.
Embodiment 11：The eosinY catalyst of 3mol%, potassium carbonate make additive, and ethanol as solvent is used for 2,5-bis
(4-methoxy-phenyl) -1,3,4-oxadiazole preparation.
The photochemical catalyst of 4- methoxy-benzoyl the hydrazines 0.083g, 3mol% of 0.5mmol are added in the reaction tube of 10ml
Then the potassium carbonate 0.138g of eosinY 0.010g and 1mmol add in 2ml alcohol solvents, with light intensity 0.4W/cm2Halogen lamp shines
It penetrates, reaction is stirred at room temperature with fan control.React 12 it is small when after, in reaction solution use column chromatography Methods For Purification product.Yield
For 65%.
Embodiment 12：The eosinY catalyst of 3mol%, potassium carbonate make additive, and ethanol as solvent is used for 2,5-di (4-
Tert-butylphenyl) -1,3,4-oxadiazole preparation.
The photochemical catalyst of 4- tertiary butyls-benzoyl hydrazine 0.089g, 3mol% of 0.5mmol is added in the reaction tube of 10ml
Then the potassium carbonate 0.138g of eosinY 0.010g and 1mmol add in 2ml alcohol solvents, with light intensity 0.4W/cm2Halogen lamp shines
It penetrates, reaction is stirred at room temperature with fan control.React 12 it is small when after, in reaction solution use column chromatography Methods For Purification product.Yield
For 71%.
Embodiment 13：The eosinY catalyst of 3mol%, potassium carbonate make additive, and ethanol as solvent is for the double (4- of 2,5-
Chlorphenyl) -1, the preparation of 3,4- oxadiazoles.
The 4- chloro- benzoyl hydrazine 0.085g, the photochemical catalyst eosinY of 3mol% of 0.5mmol is added in the reaction tube of 10ml
Then the potassium carbonate 0.138g of 0.010g and 1mmol adds in 2ml alcohol solvents, with light intensity 0.4W/cm2Halogen light irradiation, uses wind
Fan control room temperature is stirred to react.React 12 it is small when after, in reaction solution use column chromatography Methods For Purification product.Yield is 59%.
Embodiment 14：The eosinY catalyst of 3mol%, potassium carbonate make additive, and ethanol as solvent is for the double (4- of 2,5-
Bromophenyl) -1, the preparation of 3,4- oxadiazoles.
The 4- bromo- benzoyl hydrazine 0.107g, the photochemical catalyst eosinY of 3mol% of 0.5mmol is added in the reaction tube of 10ml
Then the potassium carbonate 0.138g of 0.010g and 1mmol adds in 2ml alcohol solvents, with light intensity 0.4W/cm2Halogen light irradiation, uses wind
Fan control room temperature is stirred to react.React 12 it is small when after, in reaction solution use column chromatography Methods For Purification product.Yield is 56%.
Embodiment 15：The eosinY catalyst of 3mol%, potassium carbonate make additive, and ethanol as solvent is used for 2,5- Dithiophenes
The preparation of base -1.3.4- oxadiazoles.
The photochemical catalyst eosinY of 2- thenoyl the hydrazines 0.071g, 3mol% of 0.5mmol are added in the reaction tube of 10ml
Then the potassium carbonate 0.138g of 0.010g and 1mmol adds in 2ml alcohol solvents, with light intensity 0.4W/cm2Halogen light irradiation, uses wind
Fan control room temperature is stirred to react.React 12 it is small when after, in reaction solution use column chromatography Methods For Purification product.Yield is 60%.
Claims (7)
1. the invention discloses a kind of novel synthesis of common medicine intermediate, using simple hydrazide kind compound as raw material,
The one pot process 2 under photocatalysis, 5- bis- substitute -1.3.4- oxadiazoles.Wherein using common halogen lamp as light source,
EosinY is catalyst, and potassium carbonate is additive, and ethyl alcohol is solvent, and reaction at room temperature can react generation 2,5- bis- substitutes-
1.3.4- oxadiazole.The invention has the features such as raw material sources are simple, and reaction condition is mild.Target compound general formula below figure：
2. in claim 1, R can be following several：Phenyl ring, thiphene ring containing substituent group etc..
3. in claim 1, in the synthesis of target product, light source is with common halogen lamp (0.4W/cm2).
4. in claim 1, in the synthesis of target product, eosin Y are required catalyst.
5. in claim 1, solvent described in the synthesis of target product is protic：Ethyl alcohol；Methanol；Isopropanol etc.,
In it is optimal with ethyl alcohol.
6. in claim 1, in the synthesis of target product, potassium carbonate is required additive.
7. in claim 1, in the synthesis of target product, reaction temperature, room temperature.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711440986.4A CN108084109A (en) | 2017-12-21 | 2017-12-21 | Synthesis method of 2, 5-disubstituted-1, 3, 4-oxadiazole |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711440986.4A CN108084109A (en) | 2017-12-21 | 2017-12-21 | Synthesis method of 2, 5-disubstituted-1, 3, 4-oxadiazole |
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| Publication Number | Publication Date |
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| CN108084109A true CN108084109A (en) | 2018-05-29 |
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| CN201711440986.4A Pending CN108084109A (en) | 2017-12-21 | 2017-12-21 | Synthesis method of 2, 5-disubstituted-1, 3, 4-oxadiazole |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109879865A (en) * | 2019-03-08 | 2019-06-14 | 烟台大学 | A kind of preparation method of 2- aryl -5- (2- quinolyl) -1,3,4- furodiazole compound |
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| CN109879865A (en) * | 2019-03-08 | 2019-06-14 | 烟台大学 | A kind of preparation method of 2- aryl -5- (2- quinolyl) -1,3,4- furodiazole compound |
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| CN111423394A (en) * | 2020-04-28 | 2020-07-17 | 常州大学 | Synthesis method of 1,3, 4-oxadiazole heterocyclic compound |
| CN111423394B (en) * | 2020-04-28 | 2021-11-23 | 常州大学 | Synthesis method of 1,3, 4-oxadiazole heterocyclic compound |
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