CN104030966B - 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative and preparation method thereof - Google Patents
2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative and preparation method thereof Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 44
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical class C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 claims abstract description 36
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- FRASJONUBLZVQX-UHFFFAOYSA-N 1,4-naphthoquinone Chemical class C1=CC=C2C(=O)C=CC(=O)C2=C1 FRASJONUBLZVQX-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229910021529 ammonia Inorganic materials 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 8
- -1 shown in formula I Chemical class 0.000 claims abstract description 5
- 238000000967 suction filtration Methods 0.000 claims abstract description 5
- 238000001816 cooling Methods 0.000 claims abstract description 4
- 238000010992 reflux Methods 0.000 claims abstract description 4
- 239000002994 raw material Substances 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims abstract description 3
- 239000002585 base Substances 0.000 claims description 61
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- CSFWPUWCSPOLJW-UHFFFAOYSA-N lawsone Chemical compound C1=CC=C2C(=O)C(O)=CC(=O)C2=C1 CSFWPUWCSPOLJW-UHFFFAOYSA-N 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- KOURBIFKJIEMRK-UHFFFAOYSA-N 3-amino-1,3-dihydroindol-2-one Chemical compound C1=CC=C2C(N)C(=O)NC2=C1 KOURBIFKJIEMRK-UHFFFAOYSA-N 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 11
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical group N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 9
- 239000005695 Ammonium acetate Substances 0.000 claims description 9
- 229940043376 ammonium acetate Drugs 0.000 claims description 9
- 235000019257 ammonium acetate Nutrition 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 6
- 230000002378 acidificating effect Effects 0.000 claims description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical group [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 abstract description 14
- 150000001875 compounds Chemical group 0.000 abstract description 7
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000002844 melting Methods 0.000 abstract description 2
- 230000008018 melting Effects 0.000 abstract description 2
- 239000012265 solid product Substances 0.000 description 18
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- 238000006452 multicomponent reaction Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 150000002475 indoles Chemical class 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 201000008827 tuberculosis Diseases 0.000 description 2
- 125000000182 1,4-naphthoquinonyl group Chemical group C1(C(=CC(C2=CC=CC=C12)=O)*)=O 0.000 description 1
- ITRAKBJPMLKWIW-UHFFFAOYSA-N 4-Bromoisatin Chemical compound BrC1=CC=CC2=C1C(=O)C(=O)N2 ITRAKBJPMLKWIW-UHFFFAOYSA-N 0.000 description 1
- HFZSCCJTJGWTDZ-UHFFFAOYSA-N 5,7-dimethyl-1h-indole-2,3-dione Chemical compound CC1=CC(C)=CC2=C1NC(=O)C2=O HFZSCCJTJGWTDZ-UHFFFAOYSA-N 0.000 description 1
- MBVCESWADCIXJN-UHFFFAOYSA-N 5-Bromoisatin Chemical compound BrC1=CC=C2NC(=O)C(=O)C2=C1 MBVCESWADCIXJN-UHFFFAOYSA-N 0.000 description 1
- VAJCSPZKMVQIAP-UHFFFAOYSA-N 5-methyl-1h-indole-2,3-dione Chemical compound CC1=CC=C2NC(=O)C(=O)C2=C1 VAJCSPZKMVQIAP-UHFFFAOYSA-N 0.000 description 1
- MXLDJTXXAYVWDF-UHFFFAOYSA-N 7-(trifluoromethyl)-1h-indole-2,3-dione Chemical compound FC(F)(F)C1=CC=CC2=C1NC(=O)C2=O MXLDJTXXAYVWDF-UHFFFAOYSA-N 0.000 description 1
- CRDNMYFJWFXOCH-BUHFOSPRSA-N Couroupitine B Natural products N\1C2=CC=CC=C2C(=O)C/1=C1/C2=CC=CC=C2NC1=O CRDNMYFJWFXOCH-BUHFOSPRSA-N 0.000 description 1
- 101100391174 Dictyostelium discoideum forC gene Proteins 0.000 description 1
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 description 1
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 description 1
- 208000002474 Tinea Diseases 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 230000001355 anti-mycobacterial effect Effects 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 239000002543 antimycotic Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229940094952 green tea extract Drugs 0.000 description 1
- 235000020688 green tea extract Nutrition 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/40—Nitrogen atoms, not forming part of a nitro radical, e.g. isatin semicarbazone
-
- C—CHEMISTRY; METALLURGY
- C30—CRYSTAL GROWTH
- C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
- C30B29/00—Single crystals or homogeneous polycrystalline material with defined structure characterised by the material or by their shape
- C30B29/54—Organic compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Crystallography & Structural Chemistry (AREA)
- Materials Engineering (AREA)
- Metallurgy (AREA)
- Indole Compounds (AREA)
Abstract
2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative and preparation method thereof, belongs to compou nd synthesis technical field.It is by the Isatine derivatives such as shown in formula I, 2-hydroxyl-1 as shown in formula II, 4-naphthoquinones and the ammonia source as shown in formula III are dissolved in solvent, at reflux abundant stirring reaction, and it is complete that TLC tracks to raw material reaction, cooling, suction filtration, oven dry, namely obtain target product.In preparation method of the present invention, reaction conditions is gentle, simple to operate, convenient post-treatment, yield are high, and yield is up to more than 98%, and the product melting range obtained is short, corresponding compound structure through IR,
1h? NMR,
13c? NMR and ESI-MS certification, partial target product can turn out monocrystalline.
Description
Technical field
The invention belongs to compou nd synthesis technical field, be specifically related to a kind of 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative and preparation method thereof.
Background technology
Multi-component reaction refers to that three or more compounds forms with the reactive mode for the treatment of different things alike the process (MulticomponentReactions, MCRs) that comprises the new compound of all components primary structure fragment.With classical inverse should compared with, multi-component reaction more meets the principle of Atom economy, and easy and simple to handle, and aftertreatment is relatively convenient, has very large advantage producing in the complicacy of molecular structure and diversity.Therefore, multi-component reaction is widely used in new drug design and synthesis, combinatorial chemistry and natural product synthesize.
3-amino-2-oxindole structure is present in and manyly has in bioactive natural product and pharmaceutical intermediate.It has a lot of biological activity, such as antimycotic (Eur.J.Med.Chem.2010,45,6120), antimalarial (Science2010,329,1175), anti-mycobacterium tuberculosis (Bioorg.Med.Chem.Lett.2008,18,2342), anti-oxidant (Eur.J.Med.Chem.2010,45,1068), tuberculosis (Eur.J.Med.Chem.2010,45,5653), effect such as antitumor (E.J.Med.Chem.2010,53,8319).1, 4-naphthaquinone is equally also important skeleton, also there is many such as antibacterium (Eur.J.Med.Chem.2010, 45, 2321), anticancer (Anti-canceragentsinmedicinalchemistry2006, 6, 489), anti-inflammatory (Annalsoftropicalmedicineandparasitology1978, 72, 523), antiplatelet (Arch.Pharm.2000, 333, 87), anti-tinea (Chem.Res.Toxicol.2004, 17, 55), Green Tea Extract oxidation (Pharmacology2004, 70, 195.), antiviral (Bioorg.Med.Chem.2012, 20, 1740) effect such as.
2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivatives, they are all simultaneously containing 3-amino-2-oxindole and 1,4-naphthoquinone structure, be that there is significant application value and a bioactive class new compound, but have not yet to see relevant report.
Summary of the invention
The object of the present invention is to provide the preparation method of 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative that a kind of reaction conditions is gentle, simple to operate, convenient post-treatment, yield are high.
Described 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative, is characterized in that its structural formula is as shown in formula IV,
（Ⅳ）
Wherein, R
1be a replacement or dibasic substituting group, substituting group is hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxyl group or trifluoromethyl, R
2for hydrogen or benzyl.
Described 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1, the preparation method of 4-naphthoquinone derivatives, it is characterized in that the Isatine derivatives such as shown in formula I, 2-hydroxyl-1 as shown in formula II, 4-naphthoquinones and the ammonia source as shown in formula III are dissolved in solvent, abundant stirring reaction at reflux, it is complete that TLC tracks to raw material reaction, cooling, suction filtration, oven dry, namely obtain target product, its reaction equation is:
Wherein, the R in formula I
1, R
2respectively with the R in formula IV
1, R
2identical.
The preparation method of described 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative, is characterized in that described ammonia source is ammonium acetate or ammoniacal liquor, is preferably ammonium acetate.
The preparation method of described 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative, is characterized in that described solvent is water, methyl alcohol, ethanol, Virahol, methylene dichloride, acetonitrile or tetrahydrofuran (THF), is preferably ethanol.
The preparation method of described 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative, when it is characterized in that reaction, also adds catalyzer.
The preparation method of described 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative, is characterized in that catalyzer is an acidic catalyst or basic catalyst.
The preparation method of described 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative, is characterized in that described an acidic catalyst is tosic acid, hydrochloric acid, acetic acid, aluminum chloride or magnesium chloride.
The preparation method of described 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative, is characterized in that described basic catalyst is cesium carbonate or ammoniacal liquor.
Described 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1, the preparation method of 4-naphthoquinone derivatives, it is characterized in that described Isatine derivatives, the molar ratio in 2 hydroxy 1,4 naphthoquinone (lawsone) and ammonia source is 1:1:1 ~ 2, preferred molar ratio is 1:1:1.5.
Described 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1, the cultural method of 4-naphthoquinones monocrystalline: compound (IV) is joined in acetonitrile solvent, then hydrochloric acid is added, suction filtration, obtain solid, then be dissolved in methyl alcohol, drip 2-5 and drip tetrahydrofuran (THF), volatilize under being placed in room temperature, obtain its monocrystalline.
Beneficial effect of the present invention is as follows:
In preparation method of the present invention, reaction conditions is gentle, simple to operate, convenient post-treatment, yield are high, and yield is up to more than 98%, and the product melting range obtained is short, corresponding compound structure through IR,
1hNMR,
13cNMR and ESI-MS certification, partial target product can turn out monocrystalline.
Accompanying drawing explanation
Fig. 1 is the single crystal structure figure of the target compound of the embodiment of the present invention 5.
Embodiment
In conjunction with following concrete enforcement, the present invention is described in further detail, and protection content of the present invention is not limited to following examples.Under the spirit and scope not deviating from inventive concept, the change that those skilled in the art can expect and advantage are all included in the present invention, and with appending claims protection domain.Implement process of the present invention, condition, reagent, experimental technique etc., except the following content mentioned specially, be universal knowledege and the common practise of this area, the present invention is not particularly limited content.
Embodiment 1:(IV-1) preparation of 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone
By isatin (147mg, 1mmol), 2 hydroxy 1,4 naphthoquinone (lawsone) (174mg, 1mmol), ammonium acetate (116mg, 1.5mmol) joins in ethanol (5ml), reflux, TLC follows the tracks of, and after 2h, reaction terminates, cooling, suction filtration, washing, dry, obtain orange solid product (IV-1) 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinones (314mg, 98%), m.p.266-268 DEG C.
1HNMR(500MHz,DMSO–
d 6 )δ10.64(s,1H),9.30(s,3H),7.83(d,
J=7.5Hz,2H),7.71(t,
J=7.1Hz,1H),7.59(td,
J=7.5,1.2Hz,1H),7.42(d,
J=7.4Hz,1H),7.25(td,
J=7.7,1.1Hz,1H),6.91(t,
J=7.6Hz,1H),6.87(d,
J=7.8Hz,1H)；
13CNMR(126MHz,DMSO–
d 6 )δ184.0,174.6,142.7,133.9,131.0,130.9,129.8,129.1,125.4,125.1,124.6,121.7,109.6,61.3；
ESI-MS(m/z):321.0[M+H]
+。
In above-described embodiment, ammonia source ammoniacal liquor replaces ammonium acetate, water used in solvent, methyl alcohol, Virahol, methylene dichloride, acetonitrile or tetrahydrofuran (THF) replace ethanol, add the catalyzer such as tosic acid, hydrochloric acid, acetic acid, aluminum chloride, magnesium chloride, cesium carbonate or ammoniacal liquor during reaction, all can obtain above-mentioned technique effect.
Embodiment 2:(IV-1) preparation of 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, add Glacial acetic acid (0.01ml, 0.2mmol), after backflow 2h, orange solid product (IV-1) 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone (299mg, 93%) can be obtained.
Embodiment 3:(IV-1) preparation of 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, add cesium carbonate (65mg, 0.2mmol), after backflow 2h, orange solid product (IV-1) 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone (250mg, 78%) can be obtained.
Embodiment 4:(IV-1) preparation of 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, change ammonium acetate (116mg, 1.5mmol) into ammonium acetate (100mg, 1.3mmol), after backflow 2h, orange solid product (IV-1) 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1 can be obtained, 4-naphthoquinones (273mg, 85%).
Embodiment 5:(IV-1) preparation of 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, change ethanol (5ml) into water (5ml), after backflow 2h, orange solid product (IV-1) 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone (225mg, 70%) can be obtained.
Embodiment 6:(IV-1) preparation of 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, change ammonium acetate (116mg, 1.5mmol) into ammoniacal liquor (0.2ml, 1.5mmol), after backflow 2.5h, orange solid product (IV-1) 2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1 can be obtained, 4-naphthoquinones (273mg, 82%).
Embodiment 7:(IV-2) preparation of 2-(3-amino-4-bromo-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, by isatin (147mg, 1mmol) change 4-bromo-isatin (226mg into, 1mmol), after backflow 3h, yellow solid product (IV-2) 2-(3-amino-4-bromo-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone (319mg can be obtained, 80%), m.p.225-226 DEG C.
IR(KBr,cm
-1):3629,3546,3467,3053,3041,1776,1761,1678,525；
1HNMR(500MHz,DMSO–
d 6 )δ10.95(s,1H),9.90(s,3H),7.85(d,
J=7.4Hz,1H),7.78–7.65(m,2H),7.61(t,
J=6.6Hz,1H),7.22(t,
J=7.9Hz,1H),7.15–7.04(m,1H),6.92(d,
J=7.6Hz,1H)；
13CNMR(126MHz,DMSO–
d 6 )δ183.6,178.4,174.8,171.8,145.2,134.0,133.3,131.4,130.9,128.2,125.5,125.2,118.5,109.2,108.2,63.4。
ESI-MS(m/z):398.9[M+H]
+。
Embodiment 8:(IV-3) preparation of 2-(3-amino-4,7-bis-chloro-2-oxindole alkane-3-bases)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, by isatin (147mg, 1mmol) change 4,7-bis-chlorisatide (216mg, 1mmol) into, after backflow 4h, Orange red solid product (IV-3) 2-(amino-4, the 7-bis-chloro-2-oxindole alkane-3-bases of 3-)-3-hydroxyl-1,4-naphthoquinone (300mg can be obtained, 77%), m.p.233-235 DEG C.
IR(KBr,cm
-1):3631,3532,3467,3058,3038,1783,1747,1676,669,658；
1HNMR(500MHz,DMSO–
d 6 )δ11.40(s,1H),9.87(s,3H),7.96–7.52(m,4H),7.41(d,
J=8.7Hz,1H),7.00(d,
J=8.7Hz,1H)；
13CNMR(126MHz,DMSO–
d 6 )δ183.6,178.4,174.7,171.8,142.5,134.1,133.2,131.6,131.0,130.9,128.6,127.4,125.6,125.3,123.1,113.0,107.9,63.0。
ESI-MS(m/z):389.0[M+H]
+。
Embodiment 9:(IV-4) preparation of 2-(3-amino-5-fluorine-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, by isatin (147mg, 1mmol) change 5-fluoro indigo red (165mg into, 1mmol), after backflow 2h, yellow solid product (IV-4) 2-(3-amino-5-fluorine-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone (332mg can be obtained, 77%), m.p.260-262 DEG C.
IR(KBr,cm
-1):3608,3545,3448,3093,3062,1718,1685,1674,1437；
1HNMR(500MHz,DMSO–
d 6 )δ10.65(s,1H),9.27(s,3H),7.83(d,
J=7.5Hz,2H),7.71(t,
J=7.5Hz,1H),7.60(t,
J=7.5Hz,1H),7.22(dd,
J=8.1,2.6Hz,1H),7.10(td,
J=9.1,2.6Hz,1H),6.86(dd,
J=8.5,4.3Hz,1H).
13CNMR(126MHz,DMSO–
d 6 )δ184.0,174.6,157.7(d,
J=237.0Hz),139.0,133.9,131.1,130.9,130.3,125.4,125.1,116.0(d,
J=23.0Hz),112.1(d,
J=25.0Hz),110.4(d,
J=7.8Hz),61.4。
ESI-MS(m/z):338.9[M+H]
+。
Embodiment 10:(IV-5) preparation of 2-(3-amino-5-chloro-2-oxo indoles alkane-3-base)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, by isatin (147mg, 1mmol) change 5-chlorisatide (182mg into, 1mmol), after backflow 2h, orange solid product (IV-5) 2-(3-amino-5-chloro-2-oxo indoles alkane-3-base)-3-hydroxyl-1,4-naphthoquinone (337mg can be obtained, 95%), m.p.240-242 DEG C.
IR(KBr,cm
-1):3604,3569,3450,3087,3016,1706,1674,1616,613；
1HNMR(500MHz,DMSO–
d 6 )δ10.78(s,1H),9.24(s,3H),7.83(d,
J=7.2Hz,2H),7.71(t,
J=6.7Hz,1H),7.60(t,
J=7.2Hz,1H),7.43(s,1H),7.31(d,
J=7.8Hz,1H),6.89(d,
J=8.2Hz,1H).
13CNMR(126MHz,DMSO–
d 6 )δ183.9,174.3,141.6,133.9,131.0,130.9,130.8,129.5,125.4,125.2,125.1,124.5,111.5,111.0,99.5,60.9。
HRMS(ESI)Calcd.forC
18H
11ClN
2O
4([M+H]
+):355.0486.Found:355.0488。
Embodiment 11:(IV-6) preparation of 2-(3-amino-5-bromo-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, by isatin (147mg, 1mmol) change 5-bromoisatin (226mg into, 1mmol), after backflow 2h, Orange red solid product (IV-6) 2-(3-amino-5-bromo-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone (359mg can be obtained, 90%), m.p.228-230 DEG C.
IR(KBr,cm
-1):3629,3571,3458,3068,3020,1695,1651,1631,588；
1HNMR(500MHz,DMSO–
d 6 )δ10.77(s,1H),9.23(s,3H),7.83(d,
J=7.4Hz,2H),7.70(t,
J=7.3Hz,1H),7.63–7.51(m,2H),7.42(dd,
J=8.3,1.8Hz,1H),6.84(d,
J=8.3Hz,1H).
13CNMR(126MHz,DMSO–
d 6 )δ184.0,174.2,142.0,133.9,132.3,131.3,131.1,130.9,127.2,125.5,125.1,112.8,111.6,61.0。
ESI-MS(m/z):399.0[M+H]
+。
Embodiment 12:(IV-7) preparation of 2-(3-amino-5-iodo-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, by isatin (147mg, 1mmol) change 5-iodine isatin (273mg into, 1mmol), after backflow 2h, orange solid product (IV-7) 2-(3-amino-5-iodo-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone (388mg can be obtained, 87%), m.p.197-199 DEG C.
IR(KBr,cm
-1):3606,3575,3461,3030,3004,1714,1672,1571,499;
1HNMR(500MHz,DMSO–
d 6 )δ10.75(s,1H),9.22(s,3H),7.85(t,
J=13.5Hz,2H),7.75–7.66(m,2H),7.60(t,
J=8.4Hz,2H),6.73(d,
J=8.2Hz,1H)；
13CNMR(126MHz,DMSO–
d 6 )δ184.0,174.0,142.5,138.1,133.9,132.7,131.6,131.0,130.9,125.4,125.2,112.1,83.8,60.9。
ESI-MS(m/z):446.8[M+H]
+。
Embodiment 13:(IV-8) preparation of 2-(3-amino-5-methyl-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, by isatin (147mg, 1mmol) change 5-methylisatin (161mg into, 1mmol), after backflow 2h, orange solid product (IV-8) 2-(3-amino-5-methyl-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone (318mg can be obtained, 95%), m.p.227-229 DEG C.
IR(KBr,cm
-1):3602,3585,3469,3045,3004,2630,1712,1699,1639,1539；
1HNMR(500MHz,DMSO–
d 6 )δ10.54(s,1H),9.28(s,3H),7.96–7.66(m,3H),7.59(td,
J=7.5,1.2Hz,1H),7.24(s,1H),7.05(dd,
J=7.9,0.9Hz,1H),6.77(d,
J=7.9Hz,1H),2.19(s,3H).
13CNMR(126MHz,DMSO–
d 6 )δ184.1,174.7,140.2,133.9,131.1,130.9,130.6,130.0,129.2,125.4,125.1,125.0,124.0,109.4,61.4,20.5。
ESI-MS(m/z):334.9[M+H]
+。
Embodiment 14:(IV-9) preparation of 2-(3-amino-5-methoxyl group-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, by isatin (147mg, 1mmol) change 5-methoxyl group isatin (177mg into, 1mmol), after backflow 2h, yellow solid product (IV-9) 2-(3-amino-5-methoxyl group-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone (343mg can be obtained, 95%), m.p.229-231 DEG C.
IR(KBr,cm
-1):3600,3537,3479,3050,3024,2630,1710,1691,1571,1239；
1HNMR(500MHz,DMSO–
d 6 )δ10.47(s,1H),9.25(s,3H),7.83(d,
J=6.4Hz,2H),7.71(s,1H),7.64–7.54(m,1H),7.04(s,1H),6.83(s,1H),6.80(s,1H),3.64(s,3H).
13CNMR(126MHz,DMSO–
d 6 )δ184.4,175.0,155.1,154.8,136.2,134.3,131.5,131.1,130.4,125.7,125.5,125.1,114.9,112.6,111.5,110.5,110.2,61.9,55.8。
ESI-MS(m/z):351.0[M+H]
+。
Embodiment 15:(IV-10) preparation of 2-(3-amino-5,7-dimethyl-2-oxindole alkane-3-bases)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, by isatin (147mg, 1mmol) change 5,7-dimethylisatin (175mg, 1mmol) into, after backflow 4h, Orange red solid product (IV-10) 2-(amino-5, the 7-dimethyl-2-oxindole alkane-3-bases of 3-)-3-hydroxyl-1,4-naphthoquinone (261mg can be obtained, 75%), m.p.230-232 DEG C.
IR(KBr,cm
-1):3612,3527,3450,3057,3033,2898,2757,1698,1630,1621,1470,1454；
1HNMR(500MHz,DMSO–
d 6 )δ10.60(s,1H),9.31(s,3H),7.82(d,
J=7.2Hz,2H),7.70(s,1H),7.59(t,
J=7.4Hz,1H),7.06(s,1H),6.88(s,1H),2.21(s,3H),2.15(s,3H)；
13CNMR(126MHz,DMSO–
d 6 )δ184.9,175.1,160.1,147.1,138.8,133.9,131.8,131.4,131.9,130.9,130.5,125.4,125.2,122.3,121.4,118.6,117.57,61.7,20.5,16.4。
ESI-MS(m/z):348.9[M+H]
+。
Embodiment 16:(IV-11) preparation of 2-(3-amino-6-chloro-2-oxo indoles alkane-3-base)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, by isatin (147mg, 1mmol) change 6-chlorisatide (182mg into, 1mmol), after backflow 2h, orange solid product (IV-11) 2-(3-amino-6-chloro-2-oxo indoles alkane-3-base)-3-hydroxyl-1,4-naphthoquinone (341mg can be obtained, 96%), m.p.251-253 DEG C.
IR(KBr,cm
-1):3593,3540,3477,3100,3018,1731,1681,1645,572；
1HNMR(500MHz,DMSO–
d 6 )δ10.80(s,1H),9.28(s,3H),7.83(d,
J=7.4Hz,2H),7.71(t,
J=7.3Hz,1H),7.60(t,
J=7.4Hz,1H),7.40(d,
J=8.0Hz,1H),6.97(dd,
J=8.0,1.7Hz,1H),6.88(d,
J=1.5Hz,1H).
13CNMR(126MHz,DMSO–
d 6 )δ184.0,174.6,144.2,134.0,134.0,131.1,130.9,127.9,126.1,125.4,125.2,121.4,109.6,60.8。
ESI-MS(m/z):354.9[M+H]
+。
Embodiment 17:(IV-12) preparation of 2-(3-amino-2-oxo-(7-trifluoromethyl) indoles alkane-3-base)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, by isatin (147mg, 1mmol) change 7-trifluoromethyl isatin (175mg into, 1mmol), after backflow 2h, orange solid product (IV-12) 2-(3-amino-2-oxo-(7-trifluoromethyl) indoles alkane-3-base)-3-hydroxyl-1,4-naphthoquinone (295mg can be obtained, 76%), m.p.195-197 DEG C.
IR(KBr,cm
-1):3647,3558,3483,3041,3032,1695,1684,1633,1454;
1HNMR(500MHz,DMSO–
d 6 )δ11.12(s,1H),9.34(s,3H),7.83(d,
J=7.4Hz,2H),7.70(dd,
J=14.8,7.4Hz,2H),7.59(td,
J=7.5,1.1Hz,1H),7.53(d,
J=8.0Hz,1H),7.10(t,
J=7.7Hz,1H)；
13CNMR(126MHz,DMSO–d6)δ184.0,175.1,140.1,134.0,131.2,131.0,130.9,128.6,126.9,126.2,125.5,125.2,123.61(q,
J=271.8Hz),121.8,110.5(q,
J=32.8Hz),60.0,21.0。
ESI-MS(m/z):389.0[M+H]
+。
Embodiment 18:(IV-13) preparation of 2-(3-amino-1-benzyl-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone
With the operation of embodiment 1, by isatin (147mg, 1mmol) change (1)-benzyl isatin (273mg into, 1mmol), after backflow 3h, Orange red solid product (IV-13) 2-(3-amino-1-benzyl-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone (308mg can be obtained, 75%), m.p.187-189 DEG C.
IR(KBr,cm
-1):3593,3560,3521,3086,3066,3026,2925,1714,1695,1682；
1HNMR(500MHz,DMSO–
d 6 )δ9.44(s,3H),7.85(d,
J=7.0Hz,2H),7.77–7.64(m,3H),7.61(t,
J=7.2Hz,1H),7.53(d,
J=7.2Hz,1H),7.39(t,
J=7.1Hz,2H),7.31(t,
J=6.8Hz,1H),7.23(t,
J=7.4Hz,1H),6.98(t,
J=7.3Hz,1H),6.74(d,
J=5.5Hz,1H)；
13CNMR(126MHz,DMSO–
d 6 )δ184.1,173.5,143.3,136.3,134.0,131.2,130.9,129.8,128.5,127.6,127.3,125.5,125.3,124.5,122.5,109.2,94.8,60.9,43.8。
ESI-MS(m/z):410.9[M+H]
+。
Claims (11)
1.2-(3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1, the preparation method of 4-naphthoquinone derivatives, it is characterized in that the Isatine derivatives such as shown in formula I, 2-hydroxyl-1 as shown in formula II, 4-naphthoquinones and the ammonia source as shown in formula III are dissolved in solvent, abundant stirring reaction at reflux, it is complete that TLC tracks to raw material reaction, cooling, suction filtration, oven dry, namely obtain target product, its reaction equation is:
Wherein, the R in formula I
1, R
2respectively with the R in formula IV
1, R
2identical, R
1be a replacement or dibasic substituting group, substituting group is hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxyl group or trifluoromethyl, R
2for hydrogen or benzyl.
2. the preparation method of 2-according to claim 1 (3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative, is characterized in that described ammonia source is ammonium acetate or ammoniacal liquor.
3. the preparation method of 2-according to claim 1 (3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative, is characterized in that described ammonia source is for being ammonium acetate.
4. 2-according to claim 1 (3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1, the preparation method of 4-naphthoquinone derivatives, is characterized in that described solvent is water, methyl alcohol, ethanol, Virahol, methylene dichloride, acetonitrile or tetrahydrofuran (THF).
5. the preparation method of 2-according to claim 1 (3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative, is characterized in that described solvent is ethanol.
6. the preparation method of 2-according to claim 1 (3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative, when it is characterized in that reaction, also adds catalyzer.
7. the preparation method of 2-according to claim 6 (3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative, is characterized in that catalyzer is an acidic catalyst or basic catalyst.
8. the preparation method of 2-according to claim 7 (3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative, is characterized in that described an acidic catalyst is tosic acid, hydrochloric acid, acetic acid, aluminum chloride or magnesium chloride.
9. the preparation method of 2-according to claim 7 (3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1,4-naphthoquinone derivative, is characterized in that described basic catalyst is cesium carbonate or ammoniacal liquor.
10. 2-according to claim 1 (3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1, the preparation method of 4-naphthoquinone derivatives, it is characterized in that described Isatine derivatives, the molar ratio in 2 hydroxy 1,4 naphthoquinone (lawsone) and ammonia source is 1:1:1 ~ 2.
11. 2-according to claim 1 (3-amino-2-oxindole alkane-3-base)-3-hydroxyl-1, the preparation method of 4-naphthoquinone derivatives, it is characterized in that described Isatine derivatives, the molar ratio in 2 hydroxy 1,4 naphthoquinone (lawsone) and ammonia source is 1:1:1.5.
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Non-Patent Citations (5)
| Title |
|---|
| A facile synthesis, anti-inflammatory and analgesic activity of isoxazolyl-2,3-dihydrospiro[benzo[f]isoindole-1,3"-indoline]-2",4,9-triones;Rajanarendar, E.等;《Bioorganic & Medicinal Chemistry Letters》;20130430;第23卷(第13期);第3954-3958页 * |
| Arylation of lawsone through BF3-mediated coupling of its phenyliodonium ylide with activated arenes and aromatic aldehydes;Elias Glinis等;《Tetrahedron》;20100523;第66卷;第5786-5792页 * |
| Chiral N-heterocyclic carbene ligands for asymmetric catalytic oxindole synthesis;Yi-Xia Jia等;《Chem.Commun.》;20080801;第4040–4042页 * |
| Organocatalytic asymmetric Michael addition of unprotected 3-substituted oxindoles to 1,4-naphthoquinone;Jin-Sheng Yu等;《Beilstein Journal of Organic Chemistry》;20120823;第8卷(第157期);第1360-1365页，第1363页表2，第1360页左栏第1段 * |
| Synthesis of N-Alkoxycarbonyl Ketimines Derived from Isatins and Their Application in Enantioselective Synthesis of 3-Aminooxindoles;Wenjin Yan等;《ORGANIE LETTERS》;20120427;第14卷(第10期);第2512-2515页 * |
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Denomination of invention: 2- (3-Amino-2-oxoindolane-3-yl) -3-hydroxy-1,4-naphthoquinone derivatives and their preparation method Effective date of registration: 20230601 Granted publication date: 20160302 Pledgee: China Postal Savings Bank Corporation Leling sub branch Pledgor: Leling Boao foam products Co.,Ltd. Registration number: Y2023980042497 |
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