CN105693672A - Preparation method of polysubstituted 2-imide-2H-benzopyran derivatives - Google Patents
Preparation method of polysubstituted 2-imide-2H-benzopyran derivatives Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 9
- 239000011698 potassium fluoride Substances 0.000 claims abstract description 6
- 235000003270 potassium fluoride Nutrition 0.000 claims abstract description 6
- 239000002243 precursor Substances 0.000 claims abstract description 6
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- -1 methoxyl group Chemical group 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 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 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 150000003556 thioamides Chemical class 0.000 claims description 5
- 125000003368 amide group Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 238000012545 processing Methods 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 230000004044 response Effects 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 abstract description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 abstract description 5
- 239000000047 product Substances 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 238000001953 recrystallisation Methods 0.000 abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000006555 catalytic reaction Methods 0.000 abstract description 3
- 238000001816 cooling Methods 0.000 abstract description 3
- 239000000706 filtrate Substances 0.000 abstract description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 abstract description 3
- 235000019341 magnesium sulphate Nutrition 0.000 abstract description 2
- 229910052751 metal Inorganic materials 0.000 abstract description 2
- 239000002184 metal Substances 0.000 abstract description 2
- 229910001873 dinitrogen Inorganic materials 0.000 abstract 1
- 239000012074 organic phase Substances 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- 238000001228 spectrum Methods 0.000 description 10
- 238000010189 synthetic method Methods 0.000 description 6
- 238000007363 ring formation reaction Methods 0.000 description 4
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical class C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 208000035126 Facies Diseases 0.000 description 2
- 229910019213 POCl3 Inorganic materials 0.000 description 2
- 238000005575 aldol reaction Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl chloride Substances ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 1
- QMGHHBHPDDAGGO-IIWOMYBWSA-N (2S,4R)-1-[(2S)-2-[[2-[3-[4-[3-[4-[[5-bromo-4-[3-[cyclobutanecarbonyl(methyl)amino]propylamino]pyrimidin-2-yl]amino]phenoxy]propoxy]butoxy]propoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide Chemical compound CN(CCCNC1=NC(NC2=CC=C(OCCCOCCCCOCCCOCC(=O)N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)NCC3=CC=C(C=C3)C3=C(C)N=CS3)C(C)(C)C)C=C2)=NC=C1Br)C(=O)C1CCC1 QMGHHBHPDDAGGO-IIWOMYBWSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 206010058314 Dysplasia Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229910004068 NO2Cl Inorganic materials 0.000 description 1
- 229910004057 NO2F Inorganic materials 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- TZRXHJWUDPFEEY-UHFFFAOYSA-N Pentaerythritol Tetranitrate Chemical compound [O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O TZRXHJWUDPFEEY-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 206010044302 Tracheitis Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- AFVLVVWMAFSXCK-VMPITWQZSA-N alpha-cyano-4-hydroxycinnamic acid Chemical group OC(=O)C(\C#N)=C\C1=CC=C(O)C=C1 AFVLVVWMAFSXCK-VMPITWQZSA-N 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 150000001562 benzopyrans Chemical class 0.000 description 1
- 238000011953 bioanalysis Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- ZUKSLMGYYPZZJD-UHFFFAOYSA-N ethenimine Chemical compound C=C=N ZUKSLMGYYPZZJD-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000010998 test method Methods 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
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a preparation method of polysubstituted 2-imide-2H-benzopyran derivatives and belongs to the technical field of organic synthesis. The preparation method includes adding thioacid amid and potassium fluoride into the reactor as well as solvent DMF, replacing nitrogen gas three times, dripping aryne precursor, heating by the end of the reaction, adding water after systematically cooling, and extracting three times by ethyl acetate, integrating organic phases, adding magnesium sulfate to dry and filter, rotating concentrated filtrate in an evaporator to produce raw products, and separating by recrystallization using solvent to produce the product. The preparation method of polysubstituted 2-imide-2H-benzopyran derivatives is scientific, reasonable, free of metal catalysis, simple in synthesis, high in yield and capable of purifying the product easily and the like. The reaction formula refers to the specification.
Description
Technical field
The invention belongs to technical field of organic synthesis, the preparation method being specifically related to a kind of polysubstituted 2-imines-2H-1-benzopyran derivatives。
Background technology
Benzo pyran derivative is the heterocyclic skeleton compound being widespread in nature that a class is important。A lot of .alpha.-5:6-benzopyrans and derivant thereof have extensive physiologically active and pharmacologically active, such as resisting hypertension, anti-dysplasia, anti-allergic effects, hypoglycemic activity, antibacterial and be used for treating anaphylaxis tracheitis, diabetes etc.。
Research finds, 2-imines-2H-1-benzopyran derivatives, by suppressing the activity of relevant enzyme, is expected to become a kind of approach of the treatment disease such as alzheimer, cancer, attracts attention and study (Bioorg.Med.Chem.2013,21, pp2396 2412；Bioorg.Med.Chem.2010,18, pp2485 2490)。
In addition, 2-imines-2H-1-benzopyran derivatives has also shown great application prospect as fluorescent material on active somatic cell labelling, the advantage of its hypotoxicity and specific marker organelle, it is made to have shown great application prospect (Org.Lett.2011 in bioanalysis research, 18, pp2884 2887)。
1-benzopyran derivatives has extensive use in various fields, and therefore the synthesis of these compounds has the meaning of particular importance。
The preparation method of 2-imines-2H-1-benzopyran derivatives has:
1) Yoneda synthetic method: α, β beta-unsaturated carbonyl compounds and phenol nucleophilic displacement of fluorine, then with DMF and POCl3Reaction, continuation polyphosphoric acids cyclization obtains 2-imines-2H-1-benzopyran derivatives。
2) Borisov synthetic method: aldol reaction first occurs for salicylaldhyde and alpha-cyano amide, and then cyclization obtains 2-imines-2H-1-benzopyran derivatives。
3) Chen synthetic method: aldol reaction first occurs for 1,3-dicarbonyl compound and salicylaldhyde, and cyclization obtains coumarin, and then reacts with hydrazine hydrate again, finally gives 2-imines-2H-1-benzopyran derivatives。
4) the wide synthetic method of Wang Yan: sulfonic acid nitrine and Terminal Acetylenes generate ketene-imine under copper catalysis, and the salicylaldhyde intermolecular cyclization of generation, and eliminate a part water and obtain 2-imines-2H-1-benzopyran derivatives。
Utilizing said method to prepare 2-imines-2H-1-benzopyran derivatives in the lab, there is obvious shortcoming: 1) synthesis step is many, agents useful for same POCl3There is zest。2) catalysis of reaction needed transition metal, does not meet the requirement of Green Chemistry；3) azide compounds used by easily rubs blast, and danger is higher。
Summary of the invention
In order to overcome above-mentioned the deficiencies in the prior art, the preparation method that the invention provides a kind of polysubstituted 2-imines-2H-1-benzopyran derivatives。
A kind of preparation method of polysubstituted 2-imines-2H-1-benzopyran derivatives, described polysubstituted 2-imines-2H-1-benzopyran derivatives has the structure shown in formula I:
In formula I, wherein R1Selected from hydrogen atom, methyl, methoxyl group；R2、R3And R4Selected from hydrogen atom, methyl；R5Selected from phenyl and substituted-phenyl, replacing atom is fluorine atom, chlorine atom, bromine atoms, methyl, methoxyl group, trifluoromethyl；R6Selected from phenyl, substituted-phenyl and substituted amido, it is fluorine atom, chlorine atom, bromine atoms, methyl, methoxyl group, trifluoromethyl that substituted-phenyl replaces atom, and substituted amido substituted radical is phenyl, benzyl, pyridine radicals；In reactor, add thioamides, potassium fluoride, solvent DMF, after substituting nitrogen three times, drips aryne precursor, heating, to reacting complete, after system cooling, adds water, divide three times by ethyl acetate and extract, merge organic facies, add magnesium sulfate and dry, filter, Rotary Evaporators concentrated filtrate obtains crude product, separates to obtain product by solvent recrystallization；Its chemical process is shown in reaction formula II:
The molar ratio of described thioamides, aryne precursor and potassium fluoride is 1:2:8, and solvent is selected from DMF, and needs before use through Non-aqueous processing；Response time is 9-25h；Reaction temperature is 90 DEG C, and recrystallization solvent for use selects ethanol。
The invention have the benefit that the synthetic method of polysubstituted 2-imines-2H-1-benzopyran derivatives provided by the invention is scientific and reasonable, it is possible to be synthetically derived the polysubstituted 2-imines-2H-1-benzopyran derivatives with multiple substituent group；But also have without metal catalytic, synthetic method is simple, and productivity is higher, product is prone to the features such as purification。
Accompanying drawing explanation
The compound 3a's of Fig. 1 and Fig. 2 respectively embodiment 1 preparation1HNMR and13CNMR collection of illustrative plates；
The compound 3c's of Fig. 3 and Fig. 4 respectively embodiment 3 preparation1HNMR and13CNMR collection of illustrative plates；
The compound 3i's of Fig. 5 and Fig. 6 respectively embodiment 9 preparation1HNMR and13CNMR collection of illustrative plates。
Detailed description of the invention
Below in conjunction with accompanying drawing and specific embodiment, the present invention is described in more detail:
Test method described in following embodiment, if no special instructions, is conventional method；Described reagent and material, if no special instructions, all commercially obtain。
Solvent used in following embodiment all carries out simple process through Non-aqueous processing or the molecular sieve after adding activation before using。
Embodiment 1
1) preparation of 1-benzopyran derivatives 3a
Thioamides 2a (56.8mg is added in 10mL Shrek pipe, 0.2mmol), potassium fluoride (92.6mg, 1.6mmol) with DMF (1mL), after substituting nitrogen three times, dropping aryne precursor 1a (119.3mg, 0.4mmol), it is placed in 90 DEG C of oil baths and stirs。TLC detects reaction substrate and disappears, and reaction terminates。After reaction system cooling, add 5mL water, then divide three times by 30mL ethyl acetate and extract, merge organic facies, wash with saturated NaCl and use anhydrous MgSO4Dry 30 minutes, filtering, filtrate concentrates to obtain crude product with Rotary Evaporators。Crude product, through recrystallization, obtains yellow solid, turns out to be 1-benzopyran derivatives 3a through NMR, HRMS, and its yield is 81%。
Spectrum elucidation data 3a:
1HNMR(500MHz,CDCl3): δ 12.74 (s, 1H), 8.70 (s, 1H), 7.76 (d, J=7.80Hz, 2H), 7.58 (d, J=7.45Hz, 1H), 7.52-7.45 (m, 3H), 7.40-7.37 (m, 4H), 7.27-7.23 (m, 2H), 7.17-7.15 (m, 2H)；13CNMR(125MHz,CDCl3): δ 159.9,153.4,149.3,143.8,141.8,138.3,132.9,139.5,129.0,12 9.0,125.0,124.6,124.3,123.2,121.4,120.3,119.1,115.6；HRMS (ESI-TOF): calcdforC22H17N2O2[M+H]+341.1290,found341.1285.
Embodiment 2
Replacing the 2a in example 1 with 2b, other conditions are with example 1, and experimental result is in Table 1。
Spectrum elucidation data 3b:
1HNMR(500MHz,CDCl3): δ 10.81 (s, 1H), 8.63 (s, 1H), 7.54 (d, J=7.55Hz, 1H), 7.46 (d, J=7.72Hz, 1H), 7.42-7.36 (m, 6H), 7.30 (d, J=7.10Hz, 1H), 7.25-7.17 (m, 4H), 7.10 (d, J=8.20Hz, 1H), 4.71 (d, J=5.49Hz, 2H).13CNMR(125MHz,CDCl3):δ162.2,153.3,148.9,144.1,141.4,138.4,132.6,129.3,128.8,128.6,127.5,127.2,124.6,124.4,123.1,121.2,119.0,115.4,43.8.HRMS(ESI-TOF):calcdforC23H19N2O2[M+H]+355.1447,found355.1440.
Embodiment 3
Replacing the 2a in example 1 with 2c, other conditions are with example 1, and experimental result is in Table 1。
Spectrum elucidation data 3c:
1HNMR(500MHz,CDCl3), δ 13.06 (s, 1H), 8.66 (s, 1H), 8.38-8.37 (m, 2H), 7.74 (t, J=8.44Hz, 1H), 7.56 (d, J=7.40Hz, 1H), 7.48 (t, J=7.75Hz, 1H), 7.42 (d, J=4.30Hz, 4H), 7.24-7.19 (m, 2H), 7.14 (d, J=8.25Hz, 1H), 7.05 (t, J=6.13Hz, 1H)；13CNMR(125MHz,CDCl3),δ160.4,153.5,152.8,151.8,148.4,143.8,142.1,138.0,133.0,129.5,128.8,124.9,124.6,123.5,121.1,119.8,118.9,115.6,114.9.HRMS(ESI-TOF):calcdforC21H16N3O2[M+H]+342.1243,found342.1245.
Embodiment 4
Replacing the 2a in example 1 with 2d, other conditions are with example 1, and experimental result is in Table 1。
Spectrum elucidation data 3d:
1HNMR(500MHz,DMSO-d6), δ 8.03 (d, J=7.65Hz, 2H), 7.83 (s, 1H), 7.68-7.64 (m, 2H), 7.56-7.51 (m, 3H), 7.29 (t, J=7.40Hz, 1H), 7.20 (d, J=8.20Hz, 1H), 7.13-7.05 (m, 4H)；13CNMR(125MHz,DMSO-d6), δ 197.8,164.0 (J=240.5), 158.0,152.5,146.5,141.2,140.7,138.9,137.2,136.3,134.5,13 4.0,133.9,129.6,129.5,129.4,124.0,120.7,120.5,120.4；HRMS (ESI-TOF): calcdforC22H15NO2F[M+H]+344.1087,found344.1078.
Embodiment 5
Replacing the 2a in example 1 with 2e, other conditions are with example 1, and experimental result is in Table 1。
Spectrum elucidation data 3e:
1HNMR(DMSO-d6, 500MHz): δ 8.03 (d, J=6.30Hz, 2H), 7.86 (s, 1H), 7.69-7.63 (m, 2H), 7.56-7.51 (m, 3H), 7.34-7.28 (m, 3H), 7.20 (d, J=7.40Hz, 1H), 7.04 (d, J=7.10Hz, 2H)；13CNMR(DMSO-d6, 125MHz): δ 192.9,153.2,148.1,144.5,136.4,134.2,132.5,131.3,129.8,12 9.3,129.1,129.0,128.3,124.9,124.6,119.2,116.0；HRMS (ESI-TOF): calcdforC22H15NO2Cl[M+H]+360.0791,found360.0785.
Embodiment 6
Replacing the 2a in example 1 with 2f, other conditions are with example 1, and experimental result is in Table 1。
Spectrum elucidation data 3f:
1HNMR(500MHz,DMSO-d6), δ 7.93 (d, J=7.55Hz, 2H), 7.78 (s, 1H), 7.63 (d, J=7.25Hz, 1H), 7.51 (t, J=7.48Hz, 1H), 7.35 (d, J=7.55Hz, 2H), 7.31-7.28 (m, 3H), 7.15 (d, J=8.05Hz, 1H), 7.06 (t, J=7.10Hz, 1H), 7.01 (d, J=7.45Hz, 2H), 2.39 (s, 3H)；13CNMR(125MHz,DMSO-d6), δ 192.5,153.3,147.4,145.6,144.7,135.6,134.0,132.3,131.8,13 0.0,129.7,129,2,129.1,124.8,124.4,122.7,119.3,115.9,21.6；HRMS (ESI-TOF): calcdforC23H18NO2[M+H]+340.1338,found340.1341.
Embodiment 7
Replacing the 2a in example 1 with 2g, other conditions are with example 1, and experimental result is in Table 1。
Spectrum elucidation data 3g:
1HNMR(500MHz,DMSO-d6), δ 7.97 (d, J=7.93Hz, 2H), 7.86 (s, 1H), 7.75 (d, J=7.93Hz, 2H), 7.65 (d, J=7.32Hz, 1H), 7.52 (t, J=7.93Hz, 1H), 7.31-7.27 (m, 3H), 7.16 (d, J=8.54Hz, 1H), 7.06 (t, J=7.02Hz, 1H), 7.01 (d, J=7.94Hz, 2H)；13CNMR(125MHz,DMSO-d6), δ 192.4,153.5,147.5,145.6,136.7,135.7,132.7,132.3,131.8,13 1.2,129.5,129.2,128.4,124.9,124.6,122.8,119.3,116.1；HRMS (ESI-TOF): calcdforC22H15NO2Br[M+H]+404.0286,found404.0289.
Embodiment 8
Replacing 1a, the 2h in example 1 to replace other conditions of 2a in example 1 with example 1 with 1b, experimental result is in Table 1。
Spectrum elucidation data 3h:
1HNMR(500MHz,CDCl3), δ 8.02 (d, J=7.60Hz, 2H), 7.83 (s, 1H), 7.57 (t, J=7.30Hz, 1H), 7.46 (t, J=7.60Hz, 2H), 7.32 (t, J=8.38Hz, 1H), 7.26-7.25 (m, 2H), 7.06-7.46 (m, 3H), 6.69 (d, J=8.30Hz, 1H), 6.63 (d, J=8.25Hz, 1H), 3.88 (s, 3H)；13CNMR(125MHz,CDCl3), δ 193.4,156.5,154.4,146.7,145.3,136.6,133.3,132.1,130.7,12 9.9,129.6,128.4,128.3,124.0,122.8,109.2,108.2,105.2,55.9；HRMS (ESI-TOF): calcdforC23H18NO3[M+H]+356.1281,found356.1290.
Embodiment 9
Replacing the 1a in example 1 with 1b, other conditions are with example 1, and experimental result is in Table 1。
Spectrum elucidation data 3i:
1HNMR(500MHz,CDCl3), δ 12.70 (s, 1H), 9.03 (s, 1H), 7.75 (d, J=8.10Hz, 2H), 7.44-7.40 (m, 2H), 7.38-7.34 (m, 5H), 7.20 (t, J=7.30Hz, 1H), 7.12 (t, J=7.32Hz, 1H), 6.71 (d, J=8.54Hz, 1H), 6.67 (d, J=8.30Hz, 1H), 3.94 (s, 3H)；13CNMR(125MHz,CDCl3),δ160.2,157.2,154.1,149.3,143.9,138.5,137.2,133.5,129.0,128.9,124.8,124.1,123.3,120.2,119.3,109.7,107.7,105.5,56.0.HRMS(ESI-TOF):calcdforC23H19N2O3[M+H]+371.1390,found371.1390.
Embodiment 10
Replacing 1a, the 2b in example 1 to replace the 2a in example 1 with 1b, other conditions are with example 1, and experimental result is in Table 1。
Spectrum elucidation data 3j:
1HNMR(500MHz,CDCl3), δ 10.78 (s, 1H), 8.96 (s, 1H), 7.41-7.40 (m, 2H), 7.38-7.34 (m, 5H), 7.28 (t, J=6.95Hz, 1H), 7.20 (d, J=7.75Hz, 2H), 7.16 (t, J=7.32Hz, 1H), 6.65 (t, J=9.17Hz, 2H), 4.69 (d, J=6.14Hz, 2H), 3.92 (s, 3H)；13CNMR(125MHz,CDCl3),δ162.5,157.1,154.0,148.9,144.2,138.5,136.8,133.1,128.7,128.6,127.5,127.1,124.4,123.1,119.1,109.5,107.6,105.3,55.9,43.7.HRMS(ESI-TOF):calcdforC24H21N2O3[M+H]+385.1547,found385.1547.
Table 1
Claims (3)
1. a preparation method for polysubstituted 2-imines-2H-1-benzopyran derivatives, described polysubstituted 2-imines-2H-1-benzopyran derivatives has the structure shown in formula I:
In formula I, wherein R1Selected from hydrogen atom, methyl, methoxyl group；R2、R3And R4Selected from hydrogen atom, methyl；R5Selected from phenyl and substituted-phenyl, replacing atom is fluorine atom, chlorine atom, bromine atoms, methyl, methoxyl group, trifluoromethyl；R6Selected from phenyl, substituted-phenyl and substituted amido, it is fluorine atom, chlorine atom, bromine atoms, methyl, methoxyl group, trifluoromethyl that substituted-phenyl replaces atom, and substituted amido substituted radical is phenyl, benzyl, pyridine radicals；It is characterized in that, by thioamides and aryne precursor, under potassium fluoride effect, the complete polysubstituted 2-imines-2H-1-benzopyran derivatives obtained shown in formula I of reacting by heating in solvent；This preparation method below equation represents:
2. preparation method according to claim 1, it is characterised in that the molar ratio of thioamides, aryne precursor and potassium fluoride is 1:2:8, solvent is selected from DMF, and needs before use through Non-aqueous processing。
3. preparation method according to claim 1, it is characterised in that the response time is 9-25h, reaction temperature is 90 DEG C。
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3562312A (en) * | 1966-11-04 | 1971-02-09 | Albert Eschenmoser | Manufacture of 2-substituted resorcinol derivatives |
| CN87107276A (en) * | 1986-12-10 | 1988-10-19 | 国际壳牌研究有限公司 | Substituted benzofurans and benzopyrans having herbicidal activity |
| US6136986A (en) * | 1998-12-22 | 2000-10-24 | Basf Aktiengesellschaft | Process for preparing substituted chroman derivatives |
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- 2016-04-14 CN CN201610231227.6A patent/CN105693672A/en active Pending
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|---|---|---|---|---|
| US3562312A (en) * | 1966-11-04 | 1971-02-09 | Albert Eschenmoser | Manufacture of 2-substituted resorcinol derivatives |
| CN87107276A (en) * | 1986-12-10 | 1988-10-19 | 国际壳牌研究有限公司 | Substituted benzofurans and benzopyrans having herbicidal activity |
| US6136986A (en) * | 1998-12-22 | 2000-10-24 | Basf Aktiengesellschaft | Process for preparing substituted chroman derivatives |
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| LI-RONG WEN ET AL: "Direct Construction of 2‑Aryliminochromenes from Arynes, N,S‑Keteneacetals, and DMF", 《THEJOURNAL OF ORGANIC CHEMISTRY》 * |
| 袁文揆 等: "DMF参与的三组分反应合成2H-苯并吡喃-2-亚胺化合物", 《中国化学会全国第十一届有机合成化学学术研讨会论文集》 * |
| 袁文揆: "芳炔、β-芳甲酰基二硫代羧酸酯、异腈参与的有机反应研究", 《万方学位论文全文数据库》 * |
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