CN103242223B - Preparation method of 2-pyridineoxydiaryl ketone derivative - Google Patents
Preparation method of 2-pyridineoxydiaryl ketone derivative Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 150000002576 ketones Chemical class 0.000 title abstract 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- 238000004440 column chromatography Methods 0.000 claims description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000012074 organic phase Substances 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 239000003480 eluent Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- HHUCYFOKONALDV-UHFFFAOYSA-N phenyl-(2-pyridin-2-yloxyphenyl)methanone Chemical compound C1(=CC=CC=C1)C(=O)C1=C(C=CC=C1)OC1=NC=CC=C1 HHUCYFOKONALDV-UHFFFAOYSA-N 0.000 claims 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 1
- MEAAWTRWNWSLPF-UHFFFAOYSA-N 2-phenoxypyridine Chemical compound C=1C=CC=NC=1OC1=CC=CC=C1 MEAAWTRWNWSLPF-UHFFFAOYSA-N 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- -1 aryl oxoacetic acid Chemical compound 0.000 abstract description 35
- 150000001875 compounds Chemical class 0.000 abstract description 12
- 239000003960 organic solvent Substances 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- 230000002194 synthesizing effect Effects 0.000 abstract 2
- 239000003054 catalyst Substances 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 239000007800 oxidant agent Substances 0.000 abstract 1
- 230000001590 oxidative effect Effects 0.000 abstract 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 23
- 238000005481 NMR spectroscopy Methods 0.000 description 20
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- 229910052763 palladium Inorganic materials 0.000 description 11
- 238000000034 method Methods 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 229910052709 silver Inorganic materials 0.000 description 3
- 239000004332 silver Substances 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 244000119461 Garcinia xanthochymus Species 0.000 description 2
- 235000000885 Garcinia xanthochymus Nutrition 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000003912 environmental pollution Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 150000002475 indoles Chemical class 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 229910000108 silver(I,III) oxide Inorganic materials 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
- MEYYEAUFCAFQAY-UHFFFAOYSA-N COc1cc(C(c(cccc2)c2Oc2ccccn2)=O)ccc1 Chemical compound COc1cc(C(c(cccc2)c2Oc2ccccn2)=O)ccc1 MEYYEAUFCAFQAY-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- NTJMMMGNOVCPIS-UHFFFAOYSA-N O=C(c1cccc(C(F)(F)F)c1)c1ccccc1Oc1ccccn1 Chemical compound O=C(c1cccc(C(F)(F)F)c1)c1ccccc1Oc1ccccn1 NTJMMMGNOVCPIS-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
- 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910001958 silver carbonate Inorganic materials 0.000 description 1
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
Abstract
The invention discloses a preparation method of 2-pyridineoxydiaryl ketone derivative. The preparation method comprises the following steps of: adding a catalyst, an oxidant, a 2-pyridineoxydiaryl compound and aryl oxoacetic acid to an organic solvent; heating up to 90-120 DEG C; and posttreating to obtain 2-pyridineoxydiaryl ketone derivative after the reaction is completed. The preparation method of the pyridineoxydiaryl ketone derivative disclosed by the invention is easy to operate, simple in posttreatment, strong in substrate designability, capable of designing a compound for synthesizing the needed structure according to actual needs, and stronger in practicability. Meanwhile, the compound prepared by the preparation method is good in bioactivity, can be used as the material for synthesizing various 2-pyridineoxydiaryl ketone derivative compounds and is higher in economic value.
Description
Technical field
The invention belongs to organic synthesis field, be specifically related to a kind of preparation method of 2-pyridyloxy diaryl ketone derivatives.
Background technology
2-pyridyloxy diaryl ketone is the very important organic intermediate of a class, and it, as a kind of important nitrogen heterocyclic ring, is extensively present in natural product.The mother nucleus structure of the multiple inhibitor against colon carcinoma cells compound such as, extracted during Garcinia Xanthochymus is real is exactly diaryl ketone.(Bioactive Benzophenonesfrom Garcinia xanthochymus Fruits,J.Nat.Prod.2005,68,354-360)
The derivative functionalization of this compounds causes the interest of a large amount of study on the synthesis persons.Such as its derivative can as the non-nucleoside reverse transcriptase inhibitor of anti-HIV-1 (NNRTI). (Practical snthesis of a benzophenone-based NNRT inhibitor of HIV-1, Org.Process Res.Dev.2012,16,561-566)
In addition, 2-pyridyloxy diaryl ketone will produce 2-hydroxy diaryl methanone compounds through hydrolysis, hydrolytic process simply, easy handling with realize industrialization.2-hydroxy diaryl methanone compounds is very important organic raw material, it can as the raw material of some medicines of synthesis, such as patent application WO2012041860A1 discloses a kind of method that the 2-of use dihydroxy benaophenonel synthesizes a class indole derivatives, and such indole derivatives can as a kind of histamine H
4receptor antibody.
Summary of the invention
The invention provides a kind of preparation method of 2-pyridyloxy diaryl ketone derivatives, the method step is simple, and the by product of reaction is carbonic acid gas and water, and environmental pollution is little.
A kind of preparation method of 2-pyridyloxy diaryl ketone derivatives, comprise: by catalyzer, oxygenant, 2-pyridyloxy aryl compound and aryl GA join in organic solvent, be heated to 90 ~ 120 DEG C, after reacting completely, obtain described 2-pyridyloxy diaryl ketone derivatives through aftertreatment;
The structure of described 2-pyridyloxy aryl compound is as shown in the formula (II):
(II);
The structure of described aryl GA is as shown in the formula (III):
(III);
The structure of described 2-pyridyloxy diaryl ketone derivatives is as shown in the formula (I):
(I);
In formula (I)-Shi (III): R
1for hydrogen, halogen, C
1~ C
5alkyl or C
1~ C
5alkoxyl group;
R
2for hydrogen, halogen, C
1~ C
5alkyl, C
1~ C
5alkoxyl group or trifluoromethyl;
Described catalyzer is divalent palladium catalyzer;
Described oxygenant is monovalence silver oxygenant.
Above-mentioned reaction process is shown below:
As shown in Figure 1, the possible reaction mechanism of preparation method of the present invention is as follows: described divalent palladium catalyzer and 2-pyridyloxy diaryl ketone derivatives are (with R
1=H is example) in pyridine atom N carry out coordination after, intermediate A is generated after the ortho position c h bond of 2-pyridyloxy is activated, intermediate B is formed after intermediate A and aryl GA generation metal exchange, and then there is decarboxylic reaction, generate intermediate C, there is reduction and eliminate the 2-pyridyloxy diaryl ketone derivatives described in generating in intermediate C, and discharges zeroth order palladium, then zeroth order palladium regenerates divalent palladium catalyzer under the effect of oxygenant, completes catalytic cycle.In this preparation method, having reacted rear by product is water and carbonic acid gas, and environmental pollution is little, and reaction raw materials becomes more readily available, and cost is lower.
As preferably, described R
1for hydrogen, fluorine, chlorine, bromine, methyl or methoxy, now, these 2-pyridyloxy aryl compounds (II) can select existing method to prepare, such as, 2-bromopyridine and fragrant phenol can be selected to obtain under the effect of monovalence copper and alkali.
As further preferred, described R
2for hydrogen, fluorine, chlorine, bromine, methyl, methoxyl group or trifluoromethyl, now starting aryl GA is cheaply easy to get, and reaction yield is higher.
As preferably, described organic solvent is dioxane, acetic acid or methyl-sulphoxide, and raw material, without requirement strict especially, can fully dissolve by the consumption of reaction solvent.
As preferably, described divalent palladium catalyzer comprises palladium, dichlorodiethyl nitrile palladium (Pd (CH
3cN)
2cl
2) or Palladous chloride, these divalent palladium catalyzer can be buied easily from the market.
As preferably, described monovalence silver oxygenant is Silver monoacetate, silver carbonate, silver suboxide or Silver Nitrate, and these oxygenants can be buied easily from the market.
In above-mentioned reaction, for economizing in raw materials, ensure carrying out completely of reaction, as preferably, the mol ratio of described 2-pyridyloxy aryl compound, aryl GA, catalyzer and oxygenant is 1:2-4:0.1-0.3:1-3 simultaneously.
Reacting the degree of carrying out can by TLC(thin-layer chromatography) monitor, as preferably, the reaction times is 6-12 hour, reaction times long increase reaction cost, is then difficult on the contrary ensure the complete of reaction.
As further preferred, described divalent palladium catalyzer is dichlorodiethyl nitrile palladium;
Described monovalence silver oxygenant is silver suboxide;
Temperature of reaction is 110 ~ 115 ° of C, and now, the productive rate of reaction is the highest, and side reaction is minimum.
As preferably, described 2-pyridyloxy diaryl ketone derivatives is selected from the one in compound shown in formula (I-1)-Shi (I-10):
(I-1)
(I-2)
(I-3)
(I-4)
(I-5)
(I-6)
(I-7)
(I-8)
(I-9)
(I-10)。
After above-mentioned reaction completes, available last handling process comprises: filter, silica gel mixed sample, eventually passes column chromatography purification and obtain corresponding 2-pyridyloxy diaryl ketone derivatives.
The preparation method of 2-pyridyloxy diaryl ketone derivatives of the present invention, easy handling, aftertreatment is easy, and substrate designability is strong, and can go out the compound of desired structure by design and synthesis according to actual needs, practicality is stronger.Meanwhile, the compound biological activity prepared by aforesaid method is good, can be used as Material synthesis various 2-hydroxy diaryl methanone compounds simultaneously, has higher economic worth.
Accompanying drawing explanation
Fig. 1 is the reaction mechanism figure of the preparation method of 2-pyridyloxy diaryl ketone derivatives of the present invention.
Embodiment
Embodiment 1 ~ 10
In the Schlenk pipe of 35ml, catalyzer, oxygenant, 2-pyridyloxy aryl compound (II), aryl GA (III) and organic solvent 2ml is added according to the proportioning raw materials of table 1, mixing and stirring, after having reacted according to the reaction conditions of table 2, filter, silica gel mixed sample, obtain corresponding 2-pyridyloxy diaryl ketone derivatives (I) through column chromatography (eluent is sherwood oil) purifying, reaction process is shown below:
Table 1
Table 2
In table 1 and table 2, T is temperature of reaction, and t is the reaction times, and Me is methyl, and OMe is methoxyl group, and p represents para-orientation, and m represents that ortho position replaces.
Application examples 1
The preparation of 2-dihydroxy benaophenonel (No. CAS: 117-99-7): the compound (I-1) (138mg, 0.5mmol) embodiment 1 prepared is dissolved in the toluene of 5 milliliters, adds 0.1mL Methyl triflate.Be heated to 100 ° of C, react 2 hours stopped reaction, revolve except toluene.Residue is dissolved in the methyl alcohol of 5 milliliters, adds sodium methylate (270mg, 5mmol), be heated to 80 ° of C and react 0.5 hour.Reaction solution cool to room temperature, with water and ethyl acetate layering, organic phase is collected, saturated common salt water washing, anhydrous magnesium sulfate drying, and filter, be spin-dried for and namely obtain product 2-dihydroxy benaophenonel 81mg, productive rate 82%, the nuclear magnetic data of products obtained therefrom is as follows:
1H NMR(400MHz,CDCl
3,TMS)δ12.1(s,1H),7.69-7.67(m,2H),7.61-7.58(m,2H),7.51-7.49(m,3H),7.08(d,J=8.4Hz,1H),6.90-6.86(m,1H);
13C NMR(100MHz,CDCl
3)δ201.6,163.2,137.8,136.3,133.6,131.9,129.1,128.3,119.1,118.6,118.4.
Application examples 2
The preparation of 4-methoxyl group-2-dihydroxy benaophenonel (No. CAS: 131-57-7): the compound (I-9) (153mg, 0.5mmol) embodiment 9 prepared is dissolved in the toluene of 5 milliliters, adds 0.1mL Methyl triflate.Be heated to 100 ° of C, react 2 hours stopped reaction, revolve except toluene.Residue is dissolved in the methyl alcohol of 5 milliliters, adds sodium methylate (270mg, 5mmol), be heated to 80 ° of C and react 0.5 hour.Reaction solution cool to room temperature, with water and ethyl acetate layering, organic phase is collected, saturated common salt water washing, anhydrous magnesium sulfate drying, and filter, be spin-dried for and namely obtain product 2-dihydroxy benaophenonel 96mg, productive rate 84%, the nuclear magnetic data of products obtained therefrom is as follows:
1H NMR(400MHz,CDCl
3,TMS)δ12.20(s,1H),7.69-7.54(m,2H),7.56-7.51(m,1H),7.47-7.43(m,2H),7.15(d,J=8.0Hz,1H),7.06(d,J=8.0Hz,1H),6.78-6.76(m,1H),3.89(s,3H);
13C NMR(100MHz,CDCl
3)δ201.6,153.2,148.8,137.7,131.8,128.1,124.6,124.3,119.1,117.9,116.9,56.1.
Embodiment 1 ~ 10 prepares the structure confirmation data of compound:
The structure detection data of the 2-pyridyloxy diaryl ketone derivatives prepared by embodiment 1 ~ 10 are respectively:
The nucleus magnetic resonance of the 2-pyridyloxy diaryl ketone derivatives (I-1, No. CAS: 1173294-85-3) prepared by embodiment 1 (
1h NMR and
13c NMR) detect data and be:
(I-1)
1H NMR(400MHz,CDCl
3,TMS)δ8.01(d,J=4.0Hz,1H),7.75(d,J=8.0Hz,2H),7.59-7.45(m,4H),7.35-7.28(m,4H),6.87(t,J=6.4Hz,1H),6.60(d,J=8.4Hz,1H);
13C NMR(100MHz,CDCl
3)δ195.3,162.8,151.5,146.9,139.3,137.4,132.7,132.1,130.2,129.7,127.9,124.6,122.7,118.4,111.4.
The nucleus magnetic resonance of the 2-pyridyloxy diaryl ketone derivatives (I-2, No. CAS: 1173294-97-7) prepared by embodiment 2 (
1h NMR and
13c NMR) detect data and be:
(I-2)
1H NMR(400MHz,CDCl
3,TMS)δ8.01(d,J=4.0Hz,1H),7.67(d,J=8.0Hz,2H),7.56-7.49(m,3H),7.31-7.24(m,2H),7.13(d,J=8.4Hz,2H),6.86(t,J=7.2Hz,1H),6.64(d,J=8.4Hz,1H),2.35(s,3H);
13C NMR(100MHz,CDCl
3)δ194.5,162.9,151.4,146.9,143.6,139.2,134.7,132.4,131.7,130.0,129.9,128.7,124.5,122.6,118.4,111.4,21.6.
The nucleus magnetic resonance of 2-pyridyloxy diaryl ketone derivatives (I-3) prepared by embodiment 3 (
1h NMR and
13c NMR) detect data and be:
(I-3)
1H NMR(400MHz,CDCl
3,TMS)δ8.01(d,J=4.0Hz,1H),7.55-7.51(m,3H),7.33-7.27(m,3H),7.25-7.19(m,2H),7.01(d,J=8.0,4.0Hz,1H),6.87(d,J=8.0Hz,1H),6.62(d,J=8.0Hz,1H),3.75(s,3H);
13C NMR(100MHz,CDCl
3)δ195.0,162.9,159.3,151.5,146.9,139.3,138.7,132.1,132.0,130.1,128.9,124.5,122.9,122.7,119.6,118.4,113.1,111.4,55.3.
The nucleus magnetic resonance of 2-pyridyloxy diaryl ketone derivatives (I-4) prepared by embodiment 4 (
1h NMR and
13c NMR) detect data and be:
(I-4)
1H NMR(400MHz,CDCl
3,TMS)δ8.00(d,J=4.0Hz,1H),7.78(d,J=8.4,2.8Hz,2H),7.59-7.51(m,3H),7.31(t,J=7.6Hz,1H),7.25(d,J=7.6Hz,1H),6.99(t,J=8.8Hz,2H),6.88(t,J=6.4Hz,1H),6.62(d,J=8.4Hz,1H);
13C NMR(100MHz,CDCl
3)δ193.7,165.5(J=253Hz),162.7,151.4,146.9,139.4,133.7(J=2.0Hz),132.4(J=8.9Hz),132.2,131.9,130.0,124.7,122.6,118.6,115.1(J=21.5Hz),111.4.
The nucleus magnetic resonance of 2-pyridyloxy diaryl ketone derivatives (I-5) prepared by embodiment 5 (
1h NMR and
13c NMR) detect data and be:
(I-5)
1H NMR(400MHz,CDCl
3,TMS)δ8.01(d,J=4.4Hz,1H),7.70(d,J=7.2Hz,2H),7.59-7.52(m,3H),7.34-7.25(m,4H),6.89(t,J=6.4Hz,1H),6.62(d,J=8.0Hz,1H);
13C NMR(100MHz,CDCl
3)δ194.1,162.7,151.5,146.9,139.4,139.1,135.8,132.4,131.7,131.1,130.1,128.3,124.8,122.7,118.6,111.5.
The nucleus magnetic resonance of the 2-pyridyloxy diaryl ketone derivatives (I-6, No. CAS: 1173294-98-8) prepared by embodiment 6 (
1h NMR and
13c NMR) detect data and be:
(I-6)
1H NMR(400MHz,CDCl
3,TMS)δ8.00(d,J=4.0Hz,1H),7.63-7.53(m,5H),7.46(d,J=8.8Hz,2H),7.31(t,J=7.6Hz,1H),7.26-7.24(m,1H),6.89(t,J=5.6Hz,1H),6.62(d,J=8.8Hz,1H);
13C NMR(125MHz,CDCl
3)δ194.2,162.7,151.5,146.9,139.4,136.2,132.4,131.6,131.3,131.2,130.1,127.8,124.7,122.7,118.6,111.5.
The nucleus magnetic resonance of 2-pyridyloxy diaryl ketone derivatives (I-7) prepared by embodiment 7 (
1h NMR and
13c NMR) detect data and be:
(I-7)
1H NMR(400MHz,CDCl
3,TMS)δ8.00-7.98(m,2H),7.93(d,J=8.0Hz,1H),7.70(d,J=8.0Hz,1H),7.61-7.59(m,2H),7.50-7.46(m,2H),7.35(t,J=7.2Hz,1H),7.28-7.26(m,1H),6.90-6.87(m,1H),6.55(d,J=8.0Hz,1H);
13C NMR(100MHz,CDCl
3)δ194.0,162.6,151.7,147.0,139.4,138.3,132.8(2C),131.2,130.6(q,J=33.4Hz),130.1,129.0(q,J=3.7Hz),128.6,126.5(q,J=3.4Hz),124.9,123.6(q,J=265Hz),122.8,118.7,111.3.
The nucleus magnetic resonance of 2-pyridyloxy diaryl ketone derivatives (I-8) prepared by embodiment 8 (
1h NMR and
13c NMR) detect data and be:
(I-8)
1H NMR(400MHz,CDCl
3,TMS)δ8.01(d,J=4.0Hz,1H),7.74(d,J=7.6Hz,2H),7.48-7.44(m,2H),7.38-7.36(m,2H),7.31(t,J=7.6Hz,2H),7.15(d,J=8.8Hz,1H),6.85(t,J=6.8Hz,1H),6.55(d,J=8.0Hz,1H),2.40(s,3H);
13C NMR(100MHz,CDCl
3)δ195.5,163.1,149.2,146.9,139.1,137.5,134.5,132.8,132.6,131.9,130.5,129.8,127.9,122.6,118.2,111.2,20.8.
The nucleus magnetic resonance of the 2-pyridyloxy diaryl ketone derivatives (I-9, No. CAS: 1173294-88-6) prepared by embodiment 9 (
1h NMR and
13c NMR) detect data and be:
(I-9)
1H NMR(400MHz,CDCl
3,TMS)δ8.01(d,J=5.2Hz,1H),7.74(d,J=8.0Hz,2H),7.48-7.44(m,2H),7.31(t,J=7.6Hz,2H),7.19(d,J=8.8Hz,1H),7.12-7.07(m,2H),6.84(t,J=6.4Hz,1H),6.52(d,J=8.4Hz,1H),3.83(s,3H);
13C NMR(100MHz,CDCl
3)δ195.0,163.3,156.3,146.9,144.8,139.1,137.3,132.9,132.8,129.7,127.9,124.1,118.1,118.0,114.4,111.0,55.7.
The nucleus magnetic resonance of 2-pyridyloxy diaryl ketone derivatives (I-10) prepared by embodiment 10 (
1h NMR and
13c NMR) detect data and be:
(I-10)
1H NMR(400MHz,CDCl
3,TMS)δ8.00(d,J=3.6Hz,1H),7.75(d,J=7.2Hz,2H),7.53-7.48(m,2H),7.34(t,J=8.0Hz,2H),7.28-7.26(m,3H),6.88(t,J=6.0Hz,1H),6.58(d,J=8.4Hz,1H);
13C NMR(100MHz,CDCl
3)δ193.8,162.8,159.0(J=245.3Hz),147.2(J=3.2Hz),146.8,139.4,136.8,133.5(J=7.2Hz),133.1,129.7,128.1,124.6(J=8.9Hz),118.8(J=23.9Hz),118.5,116.6(J=24.6Hz),111.3。
Claims (1)
1. a preparation method for 2-dihydroxy benaophenonel, is characterized in that, comprising:
(1) in the Schlenk pipe of 35ml, 0.3mmol Pd (OAc) is added
2, 3mmol Silver monoacetate, 1mmol 2-pyridyloxy benzene, 2mmol phenyl GA and dioxane 2ml, mixing and stirring, at 110 DEG C of temperature, react 12 hours, filter, silica gel mixed sample, 2-pyridyloxy diphenylmethanone is obtained, productive rate 82% through column chromatography purification;
Wherein, the eluent of column chromatography is sherwood oil;
(2) the 2-pyridyloxy diphenylmethanone that 138mg step (1) prepares is dissolved in the toluene of 5 milliliters, add 0.1mL Methyl triflate, be heated to 100 DEG C, react 2 hours stopped reaction, revolve except toluene, residue is dissolved in the methyl alcohol of 5 milliliters, add 270mg sodium methylate, be heated to 80 DEG C of reactions 0.5 hour, reaction solution cool to room temperature, with water and ethyl acetate layering, organic phase is collected, saturated common salt water washing, anhydrous magnesium sulfate drying, filter, be spin-dried for and namely obtain product 2-dihydroxy benaophenonel 81mg.
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