CN109575014A - Benzimidazole simultaneously [2,1-a] isoquinolinone compound and preparation method thereof - Google Patents
Benzimidazole simultaneously [2,1-a] isoquinolinone compound and preparation method thereof Download PDFInfo
- Publication number
- CN109575014A CN109575014A CN201810906823.9A CN201810906823A CN109575014A CN 109575014 A CN109575014 A CN 109575014A CN 201810906823 A CN201810906823 A CN 201810906823A CN 109575014 A CN109575014 A CN 109575014A
- Authority
- CN
- China
- Prior art keywords
- benzimidazole
- preparation
- compound
- follows
- aryl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
The invention discloses a kind of benzimidazoles simultaneously [2; 1-a] isoquinolinone compound and preparation method thereof; the present invention is using 1- methylacryloyl -2- aryl-benzimidazole and carboxylic acid as raw material; synthesizing benzimidazole simultaneously [2,1-a] compound of isobioquin group under the action of potassium persulfate and silver nitrate.Raw material is cheap and easy to get, reaction condition is mild, easy to operate, synthetic yield is high, is conducive to industrialized production.The analog derivative has a potential application in chemical industry, medicine and other fields, and the present invention is the synthesis providing method of benzimidazole simultaneously [2,1-a] compound of isobioquin group for the first time.
Description
Technical field
The present invention relates to the field of chemical synthesis, and in particular to a kind of benzimidazole simultaneously [2,1-a] isoquinolinone compound
Preparation method.
Background technique
Simultaneously [2,1-a] isoquinolinone compound is a kind of important poly-heterocyclic compounds to benzimidazole, in bioactivity point
The research fields such as son or functional material present extremely important researching value.In addition, carboxylic acid have it is cheap and easy to get, it is many kinds of
The advantages that, the research using decarboxylic reaction building carbon-carbon bond is one of the hot fields of Recent study.
Currently, being had no using the synthetic method of decarboxylic reaction building benzimidazole simultaneously [2,1-a] compound of isobioquin group
Report, therefore, simple there is an urgent need to find a kind of step, reaction condition is mild, and regioselectivity is high, the benzimidazole of high income
And the synthetic method of [2,1-a] compound of isobioquin group.
Summary of the invention
The invention proposes a kind of preparation methods of benzimidazole simultaneously [2,1-a] isoquinolines, provide a kind of mild condition,
The method of synthesizing benzimidazole easy to operate simultaneously [2,1-a] isoquinolines.The synthesising method reacting condition is mild, is easy to grasp
Make, handy and safe, raw material and catalyst are cheap and easy to get, are a kind of environmental-friendly green synthesis methods.
It realizes the technical scheme is that a kind of benzimidazole simultaneously [2,1-a] compound of isobioquin group, structural formula is such as
Under:
,
Wherein, R1For trifluoromethyl, methyl, tert-butyl, methoxyl group, chlorine, nitro；R2For ethyl, normal-butyl, isopropyl, phenyl.
The preparation method of the benzimidazole simultaneously [2,1-a] isoquinolines, steps are as follows: by 1- methylacryloyl-
2- aryl-benzimidazole, carboxylic acid and solvent are added in reaction tube, potassium peroxydisulfate and silver nitrate are then added thereto, 80oC
Return stirring 8 hours, obtain benzimidazole simultaneously [2,1-a] compound of isobioquin group.
The structural formula of the 1- methylacryloyl -2- aryl-benzimidazole is as follows:
,
Wherein R1For hydrogen, methyl, methoxyl group, chlorine, itrile group.
The solvent is that 1:1 is mixed by volume for acetonitrile and water.
1- methylacryloyl -2- aryl-the benzimidazole, carboxylic acid, potassium peroxydisulfate, silver nitrate molar ratio be 1:
2: 2: 0.15。
The reaction temperature is 80 DEG C, and the reaction time is 8 hours.
The reaction formula of preparation method of the present invention is as follows:
The beneficial effects of the present invention are: the synthetic method raw material of benzimidazole of the present invention simultaneously [2,1-a] isobioquin group
It is cheap and easy to get, reaction condition is mild, easy to operate, regioselectivity is high, yield is high, is conducive to industrialized production, be benzo miaow
The synthesis of azoles simultaneously [2,1-a] compound of isobioquin group provides approach.
Specific embodiment
Below in conjunction with the embodiment of the present invention, technical solution of the present invention is clearly and completely described, it is clear that institute
The embodiment of description is only a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention,
Those of ordinary skill in the art's every other embodiment obtained under that premise of not paying creative labor, belongs to this hair
The range of bright protection.
Embodiment 1
The preparation method of benzimidazole simultaneously [2,1-a] isoquinolines, steps are as follows:
1- methylacryloyl -2- aryl-benzimidazole (0.5 mmol), pivalic acid (1 mmol) are dissolved in 5 mL second
In the mixed solution of nitrile and water, potassium peroxydisulfate (2 mmol) and silver nitrate (0.02 mol) are then added thereto, 80oIt C return stirring 8 hours, after reaction, is extracted, dry, decompression boils off solvent, and residue separates (stone with silica gel column chromatography
Oily ether: ethyl acetate=10:1), obtain white solid.
Concrete outcome is as follows:
1H NMR (400 MHz, Chloroform-d) δ 8.53-8.46 (m, 1H), 8.44-8.34 (m, 1H),
7.89-7.79 (m, 1H), 7.59-7.38 (m, 5H), 2.64 (d, J = 14.4 Hz, 1H), 2.17 (d, J =
14.4 Hz, 1H), 1.71 (s, 3H), 0.54 (s, 9H).13C NMR (101 MHz, Chloroform-d) δ
173.45, 149.78, 144.08, 141.95, 131.42, 131.16, 127.63, 127.57, 125.88,
125.53, 122.39, 119.73, 115.81, 55.29, 47.64, 33.07, 32.04, 30.80。
Embodiment 2
The preparation method of benzimidazole simultaneously [2,1-a] isoquinolines, steps are as follows:
1- methylacryloyl -2- aryl-benzimidazole (0.5 mmol), adamantanecarboxylic acid (1 mmol) are dissolved in 5
In the mixed solution of mL acetonitrile and water, potassium peroxydisulfate (2 mmol) and silver nitrate (0.02 mol) are then added thereto,
80 oIt C return stirring 8 hours, after reaction, is extracted, dry, decompression boils off solvent, and residue is separated with silica gel column chromatography
(petroleum ether: ethyl acetate=10:1), obtains white solid.
Concrete outcome is as follows:
1H NMR (400 MHz, Chloroform-d) δ 8.49 (d, J = 7.7 Hz, 1H), 8.40 (dd, J =
7.0, 2.1 Hz, 1H), 7.84 (dd, J = 6.9, 2.0 Hz, 1H), 7.57-7.46 (m, 3H), 7.50-
7.38 (m, 3H), 2.51 (d, J = 14.5 Hz, 1H), 2.06 (d, J = 14.5 Hz, 1H), 1.64 (d,J = 12.9 Hz, 6H), 1.43 (d, J = 12.6 Hz, 3H), 1.34-1.21 (m, 3H), 1.19-1.04 (m,
6H).13C NMR (101 MHz, Chloroform-d) δ 173.42, 149.79, 144.13, 142.30, 131.49,
131.06, 127.56, 125.83 (d, J = 1.4 Hz), 125.45, 122.07, 119.71, 115.87,
56.20, 46.84, 43.46, 36.44, 34.18, 33.70, 28.40。
Embodiment 3
The preparation method of benzimidazole simultaneously [2,1-a] isoquinolines, steps are as follows:
1- methylacryloyl -2- aryl-benzimidazole (0.5 mmol), cyclopropanecarboxylic acid (1 mmol) are dissolved in 5 mL
In the mixed solution of acetonitrile and water, potassium peroxydisulfate (2 mmol) and silver nitrate (0.02 mol) are then added thereto, 80oIt C return stirring 8 hours, after reaction, is extracted, dry, decompression boils off solvent, and residue separates (stone with silica gel column chromatography
Oily ether: ethyl acetate=10:1), obtain white solid.
Concrete outcome is as follows:
1H NMR (400 MHz, Chloroform-d) δ 8.49 (dd, J = 7.9, 1.5 Hz, 1H), 8.41-
8.34 (m, 1H), 7.86-7.79 (m, 1H), 7.58 (ddd, J = 7.9, 6.8, 1.5 Hz, 1H), 7.53-
7.38 (m, 4H), 2.18 (dd, J = 13.7, 5.2 Hz, 1H), 2.00 (dd, J = 13.7, 8.6 Hz,
1H), 1.77 (s, 3H), 0.23-0.03 (m, 2H), -0.03--0.14 (m, 2H), -0.18--0.28 (m,
1H).13C NMR (101 MHz, Chloroform-d) δ 173.62, 150.15, 144.04, 142.05, 131.70,
131.40, 127.63, 126.28, 125.87-125.42 (m), 123.28, 119.73, 115.59, 49.61 (d,J = 17.0 Hz), 26.85, 6.87, 3.90, 3.65。
Embodiment 4
The preparation method of benzimidazole simultaneously [2,1-a] isoquinolines, steps are as follows:
1- methylacryloyl -2- aryl-benzimidazole (0.5 mmol), acetic acid (1 mmol) are dissolved in 5 mL acetonitriles
In the mixed solution of water, potassium peroxydisulfate (2 mmol) and silver nitrate (0.02 mol) are then added thereto, 80oC
It return stirring 8 hours, after reaction, is extracted, dry, decompression boils off solvent, and residue separates (petroleum with silica gel column chromatography
Ether: ethyl acetate=10:1), obtain white solid.
Concrete outcome is as follows:
1H NMR (400 MHz, Chloroform-d) δ 8.48 (dd, J = 8.1, 1.4 Hz, 1H), 8.42-
8.32 (m, 1H), 7.87-7.76 (m, 1H), 7.56 (td, J = 7.5, 1.5 Hz, 1H), 7.51-7.37
(m, 4H), 2.38 (ddd, J = 13.3, 11.8, 4.8 Hz, 1H), 1.95 (ddd, J = 13.4, 12.1,
4.4 Hz, 1H), 1.73 (s, 3H), 1.05-0.81 (m, 2H), 0.74 (t, J = 7.2 Hz, 3H). 13C
NMR (101 MHz, Chloroform-d) δ 173.40, 149.91, 144.09, 141.91, 131.83, 131.31,
127.60, 126.04, 125.83, 125.80, 125.49, 123.02, 119.76, 115.68, 49.48, 45.55,
28.64, 18.50, 14.00。
Embodiment 5
The preparation method of benzimidazole simultaneously [2,1-a] isoquinolines, steps are as follows:
1- methylacryloyl -2- aryl-benzimidazole (0.5 mmol), pivalic acid (1 mmol) are dissolved in 5 mL second
In the mixed solution of nitrile and water, potassium peroxydisulfate (2 mmol) and silver nitrate (0.02 mol) are then added thereto, 80oIt C return stirring 8 hours, after reaction, is extracted, dry, decompression boils off solvent, and residue separates (stone with silica gel column chromatography
Oily ether: ethyl acetate=10:1), obtain white solid.
Concrete outcome is as follows:
1H NMR (400 MHz, Chloroform-d) δ 8.45-8.34 (m, 2H), 7.81 (dd, J = 7.1,
1.8 Hz, 1H), 7.48-7.34 (m, 2H), 7.32-7.23 (m, 2H), 2.61 (d, J = 14.4 Hz, 1H),
2.14 (d, J = 14.3 Hz, 1H), 1.69 (s, 3H), 0.54 (s, 8H).13C NMR (101 MHz,
Chloroform-d) δ 173.51, 149.97, 144.16, 141.90, 141.56, 131.40, 128.69,
127.96, 125.78 (d, J = 8.0 Hz), 125.22, 119.79, 119.54, 115.70, 55.24, 47.52,
33.00, 32.01, 30.80, 21.89。
Embodiment 6
The preparation method of benzimidazole simultaneously [2,1-a] isoquinolines, steps are as follows:
1- methylacryloyl -2- aryl-benzimidazole (0.5 mmol), pivalic acid (1 mmol) are dissolved in 5 mL second
In the mixed solution of nitrile and water, potassium peroxydisulfate (2 mmol) and silver nitrate (0.02 mol) are then added thereto, 80oIt C return stirring 8 hours, after reaction, is extracted, dry, decompression boils off solvent, and residue separates (stone with silica gel column chromatography
Oily ether: ethyl acetate=10:1), obtain white solid.
Concrete outcome is as follows:
1H NMR (400 MHz, Chloroform-d) δ 8.40 (dd, J = 8.8, 1.5 Hz, 1H), 8.37-
8.30 (m, 1H), 7.79-7.72 (m, 1H), 7.43-7.29 (m, 2H), 7.03-6.93 (m, 2H), 3.85
(d, J = 2.9 Hz, 3H), 2.59 (dd, J = 14.4, 2.0 Hz, 1H), 2.09 (dd, J = 14.4, 1.9
Hz, 1H), 1.66 (d, J = 1.9 Hz, 3H), 0.54 (d, J = 2.0 Hz, 9H).13C NMR (101 MHz,
Chloroform-d) δ 173.34, 162.03, 149.87, 144.21, 143.99, 131.33, 127.76,
125.70, 124.96, 119.30, 115.50 (d, J = 18.8 Hz), 113.56, 113.06, 55.43 (d, J
= 9.5 Hz), 47.74, 33.15, 32.02, 30.80。
Embodiment 7
The preparation method of benzimidazole simultaneously [2,1-a] isoquinolines, steps are as follows:
1- methylacryloyl -2- aryl-benzimidazole (0.5 mmol), pivalic acid (1 mmol) are dissolved in 5 mL second
In the mixed solution of nitrile and water, potassium peroxydisulfate (2 mmol) and silver nitrate (0.02 mol) are then added thereto, 80oIt C return stirring 8 hours, after reaction, is extracted, dry, decompression boils off solvent, and residue separates (stone with silica gel column chromatography
Oily ether: ethyl acetate=10:1), obtain white solid.
Concrete outcome is as follows:
1H NMR (400 MHz, Chloroform-d) δ 8.46-8.33 (m, 6H), 7.87-7.78 (m, 3H),
7.52-7.39 (m, 12H), 2.64 (d, J = 14.5 Hz, 3H), 2.12 (d, J = 14.5 Hz, 3H),
1.71 (s, 9H), 1.34-1.24 (m, 1H), 0.88 (t, J = 6.7 Hz, 1H), 0.56 (s, 26H). 13C
NMR (101 MHz, Chloroform-d) δ 172.65, 148.82, 143.98, 143.68, 137.50, 131.34,
128.24, 127.74, 127.29, 126.06, 125.80, 121.01, 119.81, 115.80, 55.31, 47.69,
32.96, 32.08, 30.82。
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Within mind and principle, any modification, equivalent replacement, improvement and so on be should all be included in the protection scope of the present invention.
Claims (6)
1. a kind of benzimidazole simultaneously [2,1-a] isoquinolinone compound, it is characterised in that structural formula is as follows:
,
Wherein, R1For hydrogen, methyl, methoxyl group, chlorine, itrile group；R2For methyl, tert-butyl, adamantane, cyclopropyl, cyclobutyl.
2. the preparation method of benzimidazole simultaneously [2,1-a] compound of isobioquin group, it is characterised in that steps are as follows: by 1- methyl
Then acryloyl group -2- aryl-benzimidazole and carboxylic acid are added potassium peroxydisulfate and silver nitrate carry out instead in acetonitrile solvent
It answers, after reaction, is extracted, dry, decompression boils off solvent, obtains benzimidazole simultaneously [2,1-a] isoquinoline through column chromatography for separation
Quinoline ketone compounds.
3. the preparation method of benzimidazole according to claim 2 simultaneously [2,1-a] isoquinolinone compound, it is characterised in that
The structural formula of the 1- methylacryloyl -2- aryl-benzimidazole is as follows:
,
Wherein R1Represent the monosubstituted of one of following group: hydrogen, methyl, methoxyl group, chlorine, itrile group.
4. the preparation method of benzimidazole according to claim 2 simultaneously [2,1-a] isoquinolinone compound, feature exist
In: the 1- methylacryloyl -2- aryl-benzimidazole, carboxylic acid, potassium peroxydisulfate, silver nitrate molar ratio 1:2:2:
0.15。
5. the preparation method of benzimidazole according to claim 2 simultaneously [2,1-a] isoquinolinone compound, feature exist
In: the reaction dissolvent is mixed with water according to volume ratio 1:1 for acetonitrile.
6. the preparation method of benzimidazole according to claim 2 simultaneously [2,1-a] isoquinolinone compound, feature exist
In: the reaction temperature is 80 DEG C, and the reaction time is 8 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810906823.9A CN109575014B (en) | 2018-08-10 | 2018-08-10 | Benzimidazo [2,1-a ] isoquinolinone compound and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810906823.9A CN109575014B (en) | 2018-08-10 | 2018-08-10 | Benzimidazo [2,1-a ] isoquinolinone compound and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109575014A true CN109575014A (en) | 2019-04-05 |
| CN109575014B CN109575014B (en) | 2021-08-06 |
Family
ID=65919694
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810906823.9A Active CN109575014B (en) | 2018-08-10 | 2018-08-10 | Benzimidazo [2,1-a ] isoquinolinone compound and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109575014B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110066279A (en) * | 2019-06-12 | 2019-07-30 | 郑州大学 | Perfluoroalkyl substituted indole and isoquinoline compound and preparation method thereof |
| CN110078766A (en) * | 2019-06-13 | 2019-08-02 | 郑州大学 | Phosphonylation benzimidazole and compound of isobioquin group and preparation method thereof |
| CN113373465A (en) * | 2021-05-13 | 2021-09-10 | 北京工业大学 | Method for synthesizing silicon-based substituted benzimidazolo isoquinolinone compounds through photoelectric concerted catalysis |
| CN114105981A (en) * | 2021-12-14 | 2022-03-01 | 怀化学院 | Method for preparing benzimidazole [2,1-a ] isoquinoline-6 (5H) -ketone compound |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110224247A1 (en) * | 2010-03-12 | 2011-09-15 | H. Lundbeck A/S | Azaisoquinolinone derivatives as nk3 antagonists |
-
2018
- 2018-08-10 CN CN201810906823.9A patent/CN109575014B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110224247A1 (en) * | 2010-03-12 | 2011-09-15 | H. Lundbeck A/S | Azaisoquinolinone derivatives as nk3 antagonists |
Non-Patent Citations (3)
| Title |
|---|
| AHMED MUSTAFA ET AL.: "Reaktionen mit 5,6-Dihydro-benzimidazo[2.1-a]isochinolinon-(6)", 《LIEBIGS ANN.CHEM.》 * |
| KYALO STEPHEN KANYIVA ET AL.: "α-Amino Acid Sulfonamides as Versatile Sulfonylation Reagents: Silver-Catalyzed Synthesis of Coumarins and Oxindoles by Radical Cyclization", 《EUR.J.ORG.CHEM》 * |
| XIAO-FENG XIA ET AL.: "Sulfide and Sulfonyl Chloride as Sulfonylating Precursors for the Synthesis of Sulfone-Containing Isoquinolinonediones", 《ADV.SYNTH.CATAL.》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110066279A (en) * | 2019-06-12 | 2019-07-30 | 郑州大学 | Perfluoroalkyl substituted indole and isoquinoline compound and preparation method thereof |
| CN110078766A (en) * | 2019-06-13 | 2019-08-02 | 郑州大学 | Phosphonylation benzimidazole and compound of isobioquin group and preparation method thereof |
| CN113373465A (en) * | 2021-05-13 | 2021-09-10 | 北京工业大学 | Method for synthesizing silicon-based substituted benzimidazolo isoquinolinone compounds through photoelectric concerted catalysis |
| CN114105981A (en) * | 2021-12-14 | 2022-03-01 | 怀化学院 | Method for preparing benzimidazole [2,1-a ] isoquinoline-6 (5H) -ketone compound |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109575014B (en) | 2021-08-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109575014A (en) | Benzimidazole simultaneously [2,1-a] isoquinolinone compound and preparation method thereof | |
| CN108129288B (en) | Synthesis method of trans-3-hydroxycyclobutylformic acid | |
| CN110028489B (en) | Method for preparing benzamide compound by pressure reduction method | |
| EP3632905B1 (en) | Method for preparing n-acyl ortho-aminobenzamide | |
| Lone et al. | Metal free stereoselective synthesis of functionalized enamides | |
| AU2016203676A1 (en) | Process for the production of artemisinin intermediates | |
| CN111303028B (en) | 4-cyano-2-difluoromethyl substituted quinoline compound and synthetic method thereof | |
| CN108148070B (en) | Synthetic method of furanone isoquinolone compound | |
| CN110256342B (en) | Synthetic method of 2-cyano quinoline derivative | |
| CN105622538A (en) | One-pot high-yielding preparation of cetilistat | |
| CN110078766A (en) | Phosphonylation benzimidazole and compound of isobioquin group and preparation method thereof | |
| CN106336378B (en) | Preparation method of quinoline-2-formic ether series | |
| CN105646288B (en) | A kind of preparation method of carbamate derivatives | |
| CN104478799B (en) | The preparation method of 1,4-diallyl isoquinolin | |
| CN103755657B (en) | A kind of preparation method of Rivaroxaban intermediate | |
| CN109400507A (en) | The synthesis of Ailamode intermediate impurities | |
| CN106588761A (en) | Synthetic method for loratadine intermediate | |
| CN106588765A (en) | Method for hydroxylation of nitrogen oxide C2-position | |
| CN106748725B (en) | preparation method of 4-chloro-2-fluoro-phenylpropionic acid | |
| CN106631867B (en) | A kind of method for synthesizing 2- benzamido -3- aryl-acrylic acid esters | |
| CN103848773B (en) | A kind of method preparing two indyl fluorene derivatives | |
| KR101453413B1 (en) | Method for preparation of alpha-carboline derivatives | |
| CN102140063B (en) | A kind of method synthesizing derivative of trifluoromethyl acrylic acid | |
| CN110922402B (en) | C-3 iodo-indolizine compound and preparation method thereof | |
| CN108586255B (en) | Biphenyl compound and application thereof in preparation of 1, 8-dibromopyrene |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |