CN107353256B - Method for synthesizing 4-acetyl-1, 2, 3-triazole compound by one-pot method - Google Patents
Method for synthesizing 4-acetyl-1, 2, 3-triazole compound by one-pot method Download PDFInfo
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- -1 4-acetyl-1, 2, 3-triazole compound Chemical class 0.000 title claims abstract description 38
- 238000000034 method Methods 0.000 title claims abstract description 28
- 238000005580 one pot reaction Methods 0.000 title claims abstract description 10
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 38
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 150000001540 azides Chemical class 0.000 claims abstract description 13
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 150000001879 copper Chemical class 0.000 claims abstract description 9
- 239000003446 ligand Substances 0.000 claims abstract description 8
- 239000007800 oxidant agent Substances 0.000 claims abstract description 7
- 230000001590 oxidative effect Effects 0.000 claims abstract description 7
- 239000010949 copper Substances 0.000 claims description 13
- 229910002567 K2S2O8 Inorganic materials 0.000 claims description 9
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 3
- 229930182821 L-proline Natural products 0.000 claims description 3
- 229960002429 proline Drugs 0.000 claims description 3
- 238000001308 synthesis method Methods 0.000 claims description 3
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 claims description 2
- 239000012969 di-tertiary-butyl peroxide Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 12
- 238000003786 synthesis reaction Methods 0.000 abstract description 11
- 239000002994 raw material Substances 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
- 239000000047 product Substances 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 239000012043 crude product Substances 0.000 description 17
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 12
- 239000003208 petroleum Substances 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 238000000926 separation method Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000001228 spectrum Methods 0.000 description 8
- UDLLFLQFQMACJB-UHFFFAOYSA-N azidomethylbenzene Chemical compound [N-]=[N+]=NCC1=CC=CC=C1 UDLLFLQFQMACJB-UHFFFAOYSA-N 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- MEGPCWYKTKUKEG-UHFFFAOYSA-N 1-(2h-triazol-4-yl)ethanone Chemical class CC(=O)C=1C=NNN=1 MEGPCWYKTKUKEG-UHFFFAOYSA-N 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 4
- 239000012295 chemical reaction liquid Substances 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 238000003760 magnetic stirring Methods 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 3
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 3
- WYJOVVXUZNRJQY-UHFFFAOYSA-N 2-Acetylthiophene Chemical compound CC(=O)C1=CC=CS1 WYJOVVXUZNRJQY-UHFFFAOYSA-N 0.000 description 2
- NTPLXRHDUXRPNE-UHFFFAOYSA-N 4-methoxyacetophenone Chemical compound COC1=CC=C(C(C)=O)C=C1 NTPLXRHDUXRPNE-UHFFFAOYSA-N 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 150000001345 alkine derivatives Chemical group 0.000 description 2
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- CLENPZXNGSLLJQ-UHFFFAOYSA-N (4-bromophenyl)methanone Chemical compound BrC1=CC=C([C+]=O)C=C1 CLENPZXNGSLLJQ-UHFFFAOYSA-N 0.000 description 1
- FDGCNGPUZIIRQI-UHFFFAOYSA-N (4-methoxyphenyl)methanone Chemical compound O(C1=CC=C([C-]=O)C=C1)C FDGCNGPUZIIRQI-UHFFFAOYSA-N 0.000 description 1
- WYECURVXVYPVAT-UHFFFAOYSA-N 1-(4-bromophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Br)C=C1 WYECURVXVYPVAT-UHFFFAOYSA-N 0.000 description 1
- ZDPAWHACYDRYIW-UHFFFAOYSA-N 1-(4-fluorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(F)C=C1 ZDPAWHACYDRYIW-UHFFFAOYSA-N 0.000 description 1
- LSQARZALBDFYQZ-UHFFFAOYSA-N 4,4'-difluorobenzophenone Chemical compound C1=CC(F)=CC=C1C(=O)C1=CC=C(F)C=C1 LSQARZALBDFYQZ-UHFFFAOYSA-N 0.000 description 1
- ZRSNZINYAWTAHE-UHFFFAOYSA-N Anisaldehyde Natural products COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
- 238000006736 Huisgen cycloaddition reaction Methods 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 206010061592 cardiac fibrillation Diseases 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical group Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- CTRLRINCMYICJO-UHFFFAOYSA-N phenyl azide Chemical compound [N-]=[N+]=NC1=CC=CC=C1 CTRLRINCMYICJO-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000010490 three component reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for synthesizing a 4-acetyl-1, 2, 3-triazole compound by a one-pot method, belonging to the technical field of organic and pharmaceutical synthesis. Copper salt is used as a catalyst, a ligand and an oxidant, and aryl ketone and organic azide are used for one-pot reaction in a DMF solvent. The invention has the beneficial effects that: the method adopts cheap and easily-obtained copper salt as a catalyst, aryl ketone and organic azide react by a one-pot method, the reaction condition is mild, the yield is high, raw materials are easily obtained, and the 4-acetyl-1, 2, 3-triazole compound is conveniently and effectively synthesized.
Description
Technical Field
The invention relates to a method for synthesizing a 4-acetyl-1, 2, 3-triazole compound by a one-pot method, belonging to the technical field of organic and pharmaceutical synthesis.
Technical Field
The 1,2, 3-triazole compound is a nitrogen-containing heterocyclic compound with important physiological activity, and can be widely applied to preservatives, pesticides, optical materials, dyes, HIV-1 inhibitors, antibiotics and selectivity β3-adrenomimetic antagonists, antiviral drugs and anticonvulsants. Activity detection shows that the 4-acetyl-1, 2, 3-triazole compound can be used as a human bodyRecently, some 4-acetyl-1, 2, 3-triazole compounds can also be used as channel blockers to treat cardiac fibrillation, so that the 4-acetyl-1, 2, 3-triazole compounds can be used for treating a plurality of human major diseases such as cancer, heart disease and the like, and the market prospect is wide.
Early 1, 3-dipolar Huisgen cycloadditions of organic azides and terminal alkynes synthesized mixtures of 1, 4-disubstituted and 1, 5-disubstituted triazoles. The reaction requires a strong electron-withdrawing group as an activating group attached to an azide compound or an alkynyl group, and requires high temperature and high pressure and a long reaction time. Therefore, the use of 1, 4-disubstituted-1, 2, 3-triazole compounds in the synthesis is greatly limited.
Later, with the discovery of the "click" reaction, 4-acetyl substituted triazoles could also be prepared with terminal alkynes containing hydroxyl or carbonyl groups and azides, and oxidized to give the desired product, but this process requires noble metal catalysis, harsh reaction conditions, low selectivity, and low yields. Later, some methods for preparing 4-acetyl triazole by reacting olefin and organic azide catalyzed by small molecules were found, but the yield of the reaction is not very high due to the easy polymerization of olefin, and the industrialization is limited by conditions. Recently, there have been many reports of a method for synthesizing 4-acetyl 1,2, 3-triazole by a three-component reaction without azide, but the reaction takes a long time and the reaction conditions are severe.
In summary, the above methods for synthesizing 4-acetyl-1, 2, 3-triazole compounds all have the disadvantages of difficult formation, long reaction time, high reaction temperature, low yield, few applicable substrates, difficult synthesis, high raw material toxicity or poor safety, expensive catalyst, and the like.
Disclosure of Invention
In order to solve the defects of the prior art, the invention aims to provide a synthesis method of a 4-acetyl-1, 2, 3-triazole compound, which has the advantages of short reaction time, mild conditions, good safety and high yield.
In order to achieve the purpose, the invention is realized by the following technical scheme: a synthesis method of a 4-acetyl-1, 2, 3-triazole compound is characterized in that copper salt is used as a catalyst, a ligand and an oxidant, aryl ketone and organic azide are adopted to react in a DMF solvent in a one-pot method in a solvent, and the reaction formula is shown as I:
wherein R in the formula I1Is one of phenyl, substituted phenyl, aromatic heterocycle and substituted aromatic heterocycle; r2Is one of benzyl, substituted benzyl, phenyl, substituted phenyl, ethyl formate and alkyl.
According to the scheme, the copper salt is CuCl2,Cu(NO3)2,Cu(OAc)2And Cu (OTf)2One of them.
According to the scheme, the oxidant is K2S2O8BPO, TBHP and DTBP.
According to the scheme, the ligand is one of L-proline, phenanthroline and TMEDA.
According to the scheme, the reaction temperature of the reaction is 80-120 ℃.
According to the scheme, the molar ratio of the aryl ketone to the organic azide is 1 (1.5-2), the molar ratio of the copper salt catalyst to the aryl ketone is (0.2-0.5):1, the molar ratio of the ligand to the aryl ketone is (0.2-0.5):1, and the ratio of the aryl ketone to the solvent is 0.33 mmol: 2 mL.
The specific reaction steps are as follows: the preparation method comprises the following steps of performing magnetic stirring reaction on aryl ketone shown in the formula I, organic azide and a copper salt catalyst, an oxidant and a DMF (dimethyl formamide) solvent at the temperature of 80-120 ℃ for 3-8 hours, extracting a reaction solution after the reaction is finished, washing an organic layer, drying, distilling under reduced pressure to remove the solvent to obtain a crude product of the 4-acetyl-1, 2, 3-triazole compound, and performing column chromatography separation and purification to obtain the product of the 4-acetyl-1, 2, 3-triazole compound.
Further, the extractant used in the extraction step is ethyl acetate, the detergent used in the organic layer washing step is a saturated brine, the drying agent used in the drying step is anhydrous sodium sulfate, and the leacheate used in the step of performing column separation purification is a mixture of ethyl acetate and petroleum ether, and the volume ratio of ethyl acetate to petroleum ether is 1:5-1: 10.
The invention has the beneficial effects that: the method adopts cheap and easily-obtained copper salt as a catalyst, aryl ketone and organic azide react by a one-pot method, the reaction condition is mild, the yield is high, raw materials are easily obtained, and the 4-acetyl-1, 2, 3-triazole compound is conveniently and effectively synthesized.
Detailed Description
The present invention will be described in detail with reference to the following embodiments.
Example 1:
the synthesis of (N-benzyl-1, 2, 3-triazole-4-substituted) (phenyl) ketone has the reaction formula:
the method comprises the following specific steps: to a 50mL round bottom flask was added 0.33mmol acetophenone, 0.50mmol benzyl azide, 0.09mmol Cu (NO)3)2、1mmol K2S2O80.09mmol of TMEDA and 3mL of DMF, performing magnetic stirring reaction at 110 ℃ for 5 hours, extracting a reaction solution by using ethyl acetate, washing an organic layer by using saturated saline solution, drying anhydrous sodium sulfate, and then evaporating a solvent under reduced pressure to obtain a crude product, wherein the crude product is subjected to column separation and purification by using ethyl acetate/petroleum ether (1: 5) (V/V) as eluent to obtain the required product, the product is a white solid, and the yield is 80%.
The nuclear magnetic hydrogen spectrum result of the obtained product is as follows:1H NMR(600MHz,CDCl3)δ8.46–8.39(m,1H),8.17(s,1H),7.61(m,J＝10.8,3.9Hz,1H),7.51(t,J＝7.8Hz,1H),7.40(d,J＝6.9Hz,1H),7.33(d,J＝7.5Hz,1H),5.60(s,1H).
example 2:
the synthesis of (N-benzyl-1, 2, 3-triazole-4-substituted) (4-methoxyphenyl) methanone has the following reaction formula:
the method comprises the following specific steps: to a 50mL round bottom flask were added 0.33mmol of 4-methoxyacetophenone, 0.50mmol of benzyl azide, 0.09mmol of Cu (NO)3)2、1mmol K2S2O80.09mmol of TMEDA and 3mL of DMF are magnetically stirred at 110 ℃ for reaction for 5 hours, ethyl acetate is used for extracting reaction liquid, an organic layer is washed by saturated saline solution, after anhydrous sodium sulfate is dried, a solvent is evaporated under reduced pressure to obtain a crude product, the crude product is subjected to column separation and purification by taking ethyl acetate/petroleum ether (1: 5 (V/V)) as eluent to obtain the required product, the product is a white solid, and the yield is 85%.
The nuclear magnetic hydrogen spectrum result of the obtained product is as follows:1H NMR(600MHz,CDCl3)δ8.34(d,J＝8.1Hz,2H),8.16(s,1H),7.33(m,7H),5.59(s,2H),3.41(s,3H).
example 3:
the synthesis of (N-benzyl-1, 2, 3-triazole-4-substituted) (4-fluorophenyl) ketone has the following reaction formula:
the method comprises the following specific steps: to a 50mL round bottom flask was added 0.33mmol 4-fluoroacetophenone, 0.50mmol benzyl azide, 0.09mmol Cu (NO)3)2、1mmol K2S2O80.09mmol of TMEDA and 3mL of DMF are magnetically stirred at 110 ℃ for reaction for 5 hours, ethyl acetate is used for extracting reaction liquid, an organic layer is washed by saturated saline solution, after anhydrous sodium sulfate is dried, a solvent is evaporated under reduced pressure to obtain a crude product, the crude product is subjected to column separation and purification by taking ethyl acetate/petroleum ether (1: 5 (V/V)) as eluent to obtain the required product, the product is a white solid, and the yield is 87%.
The nuclear magnetic hydrogen spectrum result of the obtained product is as follows:1H NMR(600MHz,CDCl3)δ8.53(m,2H),8.18(s,1H),7.45–7.31(m,5H),7.21–7.14(m,2H),5.61(s,2H).
example 4:
the synthesis of (N-benzyl-1, 2, 3-triazole-4-substituted) (phenyl) ketone has the reaction formula:
the method comprises the following specific steps: to a 50mL round bottom flask was added 0.33mmol 2-acetylthiophene, 0.50mmol benzyl azide, 0.09mmol Cu (NO)3)2、1mmol K2S2O80.09mmol of TMEDA and 3mL of DMF are magnetically stirred at 110 ℃ for reaction for 5 hours, ethyl acetate is used for extracting reaction liquid, an organic layer is washed by saturated saline solution, after anhydrous sodium sulfate is dried, a solvent is evaporated under reduced pressure to obtain a crude product, the crude product is subjected to column separation and purification by taking ethyl acetate/petroleum ether (1: 5 (V/V)) as eluent to obtain the required product, the product is a white solid, and the yield is 80%.
The nuclear magnetic hydrogen spectrum result of the obtained product is as follows:1HNMR(600MHz,CDCl3)δ8.75(d,J＝3.9Hz,1H),8.15(s,1H),7.75(d,J＝4.8Hz,1H),7.43–7.38(m,3H),7.35–7.30(m,2H),7.23(t,J＝4.5Hz,1H),5.61(s,2H).
example 5:
the synthesis of (N-phenyl-1, 2, 3-triazole-4-substituted) (phenyl) methanone has the reaction formula:
the method comprises the following specific steps: a50 mL round bottom flask was charged with 0.33mmol acetophenone, 0.50mmol phenyl azide, 0.09mmol Cu (NO)3)2、1mmol K2S2O8Magnetic stirring 0.09mmol of TMEDA and 3mL of DMF at 110 ℃ for reaction for 5 hours, extracting the reaction solution by using ethyl acetate, washing an organic layer by using saturated saline solution, drying the organic layer by using anhydrous sodium sulfate, and then evaporating the solvent under reduced pressure to obtain a crude product, wherein the crude product, namely ethyl acetate/petroleum ether, is 1:5(V/V) and is used as eluent to carry out column chromatographySeparating and purifying to obtain the required product, wherein the product is a white solid, and the yield is 80%.
The nuclear magnetic hydrogen spectrum result of the obtained product is as follows:1H NMR(600MHz,CDCl3)δ8.46–8.39(m,1H),8.17(s,1H),7.61(m,J＝10.8,3.9Hz,1H),7.51(t,J＝7.8Hz,1H),7.40(d,J＝6.9Hz,1H),7.33(d,J＝7.5Hz,1H),5.60(s,1H).
example 6:
the synthesis of (N-benzyl-1, 2, 3-triazole-4-substituted) (phenyl) ketone has the reaction formula:
the method comprises the following specific steps: to a 50mL round bottom flask were added 0.33mmol acetophenone, 0.50mmol benzyl azide, 0.09mmol CuSO4、1mmol K2S2O80.09mmol of L-proline and 3mL of DMF are magnetically stirred at 110 ℃ for reaction for 5 hours, then ethyl acetate is used for extracting reaction liquid, an organic layer is washed by saturated saline solution, after anhydrous sodium sulfate is dried, a solvent is evaporated under reduced pressure to obtain a crude product, the crude product, namely ethyl acetate/petroleum ether 1:5(V/V), is used as eluent to carry out column separation and purification, and the required product is obtained, namely a white solid, and the yield is 83%.
The nuclear magnetic hydrogen spectrum result of the obtained product is as follows:1H NMR(600MHz,CDCl3)δ8.46–8.39(m,1H),8.17(s,1H),7.61(m,J＝10.8,3.9Hz,1H),7.51(t,J＝7.8Hz,1H),7.40(d,J＝6.9Hz,1H),7.33(d,J＝7.5Hz,1H),5.60(s,1H).
example 7:
the synthesis of (N-benzyl-1, 2, 3-triazole-4-substituted) (phenyl) ketone has the reaction formula:
the method comprises the following specific steps: to a 50mL round bottom flask was added 0.33mmol acetophenone, 0.50mmol benzyl azide, 0.09mmol Cu (NO)3)21mmol of TBHP and 3mL of DMF, magnetically stirring at 110 ℃ for 5 hours, and extracting the reaction solution with ethyl acetate to obtainWashing the organic layer with saturated saline water, drying with anhydrous sodium sulfate, and evaporating the solvent under reduced pressure to obtain a crude product, wherein the crude product ethyl acetate/petroleum ether (1: 5 (V/V)) is used as eluent to perform column separation and purification to obtain the required product, the product is a white solid, and the yield is 79%.
The nuclear magnetic hydrogen spectrum result of the obtained product is as follows:1H NMR(600MHz,CDCl3)δ8.46–8.39(m,1H),8.17(s,1H),7.61(m,J＝10.8,3.9Hz,1H),7.51(t,J＝7.8Hz,1H),7.40(d,J＝6.9Hz,1H),7.33(d,J＝7.5Hz,1H),5.60(s,1H).
example 8:
(N-ethyl acetate-1, 2, 3-triazole-4-substituted) (4-bromo-phenyl) methanone, wherein the reaction formula is as follows:
the method comprises the following specific steps: to a 50mL round bottom flask were added 0.33mmol of p-bromoacetophenone, 0.50mmol of ester azide, 0.09mmol of Cu (NO)3)21mmol of TBHP, 0.09mmol of TMEDA and 3mL of DMF, performing magnetic stirring reaction at 110 ℃ for 5 hours, extracting the reaction solution by using ethyl acetate, washing an organic layer by using saturated saline solution, drying the organic layer by using anhydrous sodium sulfate, and then performing reduced pressure evaporation to remove the solvent to obtain a crude product, wherein the crude product, namely ethyl acetate/petroleum ether (1: 5 (V/V)), is eluent to perform column separation and purification to obtain the required product, the product is a white solid, and the yield is 75%.
The nuclear magnetic hydrogen spectrum result of the obtained product is as follows:1H NMR(600MHz,CDCl3)δ8.42(s,1H),8.39–8.31(m,2H),7.72–7.63(m,2H),7.26(s,1H),5.26(s,2H),4.32(q,J＝7.2Hz,2H),1.33(t,J＝7.2Hz,3H).
the invention adopts cheap and easily obtained copper salt as a catalyst to replace ketone and organic azide one-pot reaction, so as to conveniently and effectively synthesize the 4-acetyl-1, 2, 3-triazole compound.
The above embodiments do not limit the present invention in any way, and all technical solutions obtained by means of equivalent substitution or equivalent minor changes fall within the scope of the present invention.
Claims (3)
1. A synthesis method of a 4-acetyl-1, 2, 3-triazole compound is characterized in that Cu salt is used as a catalyst, a ligand and an oxidant, aryl ketone and organic azide are adopted to react in a DMF solvent in a one-pot method in a solvent, and the reaction formula is shown as I:
wherein, in formula I, R1R when it is phenyl2Is one of benzyl and phenyl, or when R is1R is one of 4-methoxyphenyl, 4-fluorophenyl and 2-thienyl2Is benzyl, or when R is1R is 4-bromophenyl2Is ethoxycarbonylmethyl, and the Cu salt is Cu (NO)3)2And the ligand is TMEDA and the oxidant is K2S2O8Or DTBP, or the Cu salt is CuSO4And the ligand is L-proline and the oxidant is K2S2O8。
2. The method for synthesizing 4-acetyl-1, 2, 3-triazole compound according to claim 1, wherein the reaction temperature of the reaction is 80 to 120 ℃.
3. The method of claim 1, wherein the molar ratio of aryl ketone to organic azide is 1:1.5-2, the molar ratio of copper salt catalyst to aryl ketone is 0.2-0.5:1, the molar ratio of ligand to aryl ketone is 0.2-0.5:1, the ratio of aryl ketone to solvent is 0.33 mmol: 2 mL.
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| CN1671673A (en) * | 2002-05-30 | 2005-09-21 | 斯克里普斯研究学院 | Copper-catalysed ligation of azides and acetylenes |
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