CN106866545B - 1- cycloalkane -5- nitro -1H- benzo [D] glyoxaline compound and preparation method thereof - Google Patents
1- cycloalkane -5- nitro -1H- benzo [D] glyoxaline compound and preparation method thereof Download PDFInfo
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- CN106866545B CN106866545B CN201710204976.4A CN201710204976A CN106866545B CN 106866545 B CN106866545 B CN 106866545B CN 201710204976 A CN201710204976 A CN 201710204976A CN 106866545 B CN106866545 B CN 106866545B
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- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- -1 glyoxaline compound Chemical class 0.000 title claims description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 150000001412 amines Chemical class 0.000 claims abstract description 8
- 238000013019 agitation Methods 0.000 claims abstract description 6
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000000047 product Substances 0.000 claims abstract description 6
- 239000011541 reaction mixture Substances 0.000 claims abstract description 6
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000007795 chemical reaction product Substances 0.000 claims abstract description 5
- 238000004366 reverse phase liquid chromatography Methods 0.000 claims abstract description 5
- 229940126214 compound 3 Drugs 0.000 claims description 2
- 150000001924 cycloalkanes Chemical class 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 229910052731 fluorine Inorganic materials 0.000 abstract description 2
- 239000011737 fluorine Substances 0.000 abstract description 2
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 238000007363 ring formation reaction Methods 0.000 abstract description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 abstract 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 2
- 150000001556 benzimidazoles Chemical class 0.000 description 2
- 244000045947 parasite Species 0.000 description 2
- 238000003786 synthesis reaction 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
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
- UXGJAOIJSROTTN-UHFFFAOYSA-N 2-[4-(4-chlorophenoxy)phenyl]-3h-benzimidazole-5-carboxamide Chemical compound N1C2=CC(C(=O)N)=CC=C2N=C1C(C=C1)=CC=C1OC1=CC=C(Cl)C=C1 UXGJAOIJSROTTN-UHFFFAOYSA-N 0.000 description 1
- ZCUJYXPAKHMBAZ-UHFFFAOYSA-N 2-phenyl-1h-imidazole Chemical compound C1=CNC(C=2C=CC=CC=2)=N1 ZCUJYXPAKHMBAZ-UHFFFAOYSA-N 0.000 description 1
- 229910000975 Carbon steel Inorganic materials 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 240000005308 Juniperus chinensis Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 230000003356 anti-rheumatic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002543 antimycotic Substances 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- OSVHLUXLWQLPIY-KBAYOESNSA-N butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate Chemical compound C(CCC)OC(C(C)(C)C1=CC(=C2[C@H]3[C@H](C(OC2=C1)(C)C)CC[C@H](C3)CO)O)=O OSVHLUXLWQLPIY-KBAYOESNSA-N 0.000 description 1
- 239000010962 carbon steel Substances 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
Abstract
The invention discloses a kind of 1- cycloalkane -5- nitro -1H- benzo [D] glyoxaline compounds and preparation method thereof, in the flask with magnetic agitation, N ' (2-F-5- nitrobenzene)-N of 0.4mmol is added, N- dimethyl-formamidine, the amine of 0.5mL dry HMPA and 2.8mmol, reaction mixture heats 70-120min at 150-230 DEG C, and reaction product obtains target product compound after Reverse phase chromatography.Preparation method of the present invention is simple, such compound of one pot process (amine replaces fluorine and cyclization), it is compared with the traditional method and shows high selectivity, raw material is easy to get, benzimidazole group exists in many drug molecules in gained compound structure, nitro in molecule can be reduced to amino, and therefore, such compound can be used widely.
Description
Technical field
The present invention relates to the benzimidazole compounds of a kind of N- naphthenic base replaced, and in particular to 1- cycloalkane -5- nitro -
1H- benzo [D] glyoxaline compound and preparation method thereof.
Background technique
In decades, the synthesis and application study of benzimidazole and its derivative are the research hotspots of Minute Organic Synthesis；
Benzimidazoles compound is a kind of containing there are two the Benzoheterocyclic compounds of nitrogen-atoms, benzimidazole and its derivatives anti-
Cancer, antimycotic, easing pain and diminishing inflammation, antirheumatic, expelling parasite etc. have critically important medical value.Benzimidazoles compound or one
The excellent corrosion inhibiter that kind is corroded in acidic environment for carbon steel；Su Guoqiang, Guo Diliang, Liu Yu, Zhu Lan, Bian Jun, Zhu Chongliang report
The road preparation method (CN1425654A) of 2- alkoxybenzimidazole compound.
Li Yan, Ma Huiqiang, Wang Yulu report a series of benzimidazoles and derivative (organic chemistry, the 2nd phase in 2008,
210~217).
Zeng Qingle etc. reports the synthetic method (103755642 A of CN) of 2- aryl benzimidazole.
Hao Xinqi etc. discloses 3- (2- nitro -1- phenethyl) -2- (2- phenylimidazole simultaneously [1,2- α] pyridine) class compound
(CN 105085520 A)。
Old Chinese juniper China, Lin Weizhong are condensed to form the double Schiff's bases of intramolecular using o-phenylenediamine and two molecule aldehyde, are divided by occurring
It is reset in sub and has synthesized 1- substitution -2- aryl benzimidizole derivatives.
Benzimidazoles compound not only has the bioactivity such as sterilization, antitumor, expelling parasite, but also due to depositing in its structure
Nitro in strong electron-withdrawing group nitro, molecule can also be reduced to amino, and therefore, such compound can be used widely.
In conclusion the benzimidazoles compound of research and development structure novel, performance efficiency has important reality meaning
Justice and scientific value.There is no 1- cycloalkane -5- nitro -1H- benzene in published benzimidazoles compound documents and materials
And [D] glyoxaline compound.
Summary of the invention
The purpose of the present invention is to provide 1- cycloalkane -5- nitro -1H- benzo [D] glyoxaline compound and its preparation sides
Method, to solve the above technical problems.
To achieve the above object, the technical solution adopted by the present invention is that:
1- cycloalkane -5- nitro -1H- benzo [D] glyoxaline compound, the compound are following general formula compound represented
3:
Wherein: R △,,
The present invention also provides the preparation methods of 1- cycloalkane -5- nitro -1H- benzo [D] glyoxaline compound, are having
In the flask of magnetic agitation, it is added N ' (2-F-5- nitrobenzene)-N of 0.4mmol, N- dimethyl-formamidine, 0.5mL is dry
Reaction mixture is heated 70-120min by the amine 2 of HMPA and 2.8mmol at 150-230 DEG C, and reaction product passes through reverse phase color
Spectrum obtains target product compound 3 after purification.
The invention has the benefit that preparation method of the present invention is simple, (amine replaces fluorine for one pot process such compound
And cyclization), it is compared with the traditional method and shows high selectivity, raw material is easy to get, benzo miaow in gained compound structure
Oxazolyl group exists in many drug molecules, and the nitro in molecule can be reduced to amino, such compound is widely used.
Specific embodiment
The present invention is further elaborated combined with specific embodiments below.
Embodiment 1
Preparation method:
In a reaction tube with magnetic agitation, N ' (2-F-5- nitrobenzene)-N, N- dimethyl-formamidine is added
(0.4mmol), 0.5mL dry HMPA and amine 2a (2.8mmol), reaction mixture heat 100min at 180 DEG C, and reaction produces
Object obtains target product compound 3a after Reverse phase chromatography.Yield is 22%.1H NMR (500MHz, MeOD): δ ppm
1.07-1.17 (m, 2H), 1.21-1.32 (m, 2H), 3.60 (dt, J=7.02,3.51Hz, 1H), 7.81-7.88 (m, 1H),
8.22-8.32 (m, 1H), 8.45 (s, 1H), 8.55 (br.s., 1H)；13C NMR (126MHz, MeOD): δ ppm 5.32,
42.80,11.31,115.63,118.80,139.51,142.57,144.46,148.01；HRMS calcd.for C10H9N3O2:
203.0695, found:203.0682.
Embodiment 2
Preparation method: in a reaction tube with magnetic agitation, N ' (2-F-5- nitrobenzene)-N, N- diformazan is added
Base-carbonamidine (0.4mmol), 0.5mL dry HMPA and amine 2b (3.3mmol), reaction mixture heat 80min at 230 DEG C,
Reaction product obtains target product compound 3b after Reverse phase chromatography.Yield is 51%.
1H NMR (500MHz, MeOD): δ ppm 1.94-2.15 (m, 2H), 2.51-2.73 (m, 4H), 4.98-5.10 (m,
1H), 7.72 (d, J=8.85Hz, 1H), 8.20 (d, J=8.85Hz, 1H), 8.54 (d, J=8.85Hz, 2H)；13C NMR
(126MHz, MeOD): δ ppm 15.12,29.83,47.50,47.66,47.84,48.01,48.18,48.35,48.52,
48.63,48.66,50.46,111.27,115.61,118.50,137.66,142.76,144.22,145.75；HRMS
calcd.for C11H11N3O2: 217.0851, found:217.0838.
Embodiment 3
Preparation method: in a reaction tube with magnetic agitation, N ' (2-F-5- nitrobenzene)-N, N- diformazan is added
Base-carbonamidine (0.4mmol), 0.5mL dry HMPA and amine 2c (3.3mmol), reaction mixture heat 90min at 220 DEG C,
Reaction product obtains target product compound 3c after Reverse phase chromatography.Yield is 37%.1H NMR(500MHz,
MeOD): δ ppm 1.47-1.58 (m, 4H), 1.81-2.06 (m, 4H), 3.79-3.86 (m, 1H), 7.71 (d, J=8.85Hz,
1H), 8.19 (d, J=8.85Hz, 1H), 8.53 (d, J=8.85Hz, 2H)；HRMS calcd.for C12H13N3O2:
231.1008, found:231.1004.
Obviously, embodiments described above is only a part of the embodiment of the present invention, instead of all the embodiments.Base
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts it is all its
His embodiment, shall fall within the protection scope of the present invention.
Claims (1)
- The preparation method of cycloalkane 1.1- -5- nitro -1H- benzo [D] glyoxaline compound, which is characterized in that the compound is Following general formula compound represented 3:Wherein: R is、、、；In the flask with magnetic agitation, N ' (2-F-5- nitrobenzene)-N of 0.4 mmol of addition, N- dimethyl-formamidine, The amine 2 of 0.5 mL dry HMPA and 2.8 mmol, by reaction mixture 150-230o70-120 min is heated under C, Reaction product obtains target product compound 3 after Reverse phase chromatography.
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| CN107445899A (en) * | 2017-07-19 | 2017-12-08 | 枣庄学院 | A kind of benzimidazoles compound and preparation method thereof |
| CN108863820B (en) * | 2018-07-30 | 2021-07-06 | 枣庄学院 | Synthesis method of substituted o-phenylenediamine |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2004092181A1 (en) * | 2003-04-11 | 2004-10-28 | Smithkline Beecham Corporation | Heterocyclic mchr1 antagonists |
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| WO2004092181A1 (en) * | 2003-04-11 | 2004-10-28 | Smithkline Beecham Corporation | Heterocyclic mchr1 antagonists |
Non-Patent Citations (4)
| Title |
|---|
| Copper- and Palladium-Catalyzed Intramolecular Aryl Guanidinylation: An Efficient Method for the Synthesis of 2-Aminobenzimidazoles;Ghotas Evindar et al.,;《Org. Lett.》;20021219;第5卷(第2期);第133-136页 |
| Synthesis and Biological Activities of Some Benzimidazoles Derivatives;HAMDAN S. AL-EBAISAT;《J. Appl. Sci. Environ. Manage. Sept》;20111231;第15卷(第3期);第451-453页 |
| Synthesis and Biological Activities of Some Benzimidazoles Derivatives;HAMDAN S. AL-EBAISAT;《J. Appl. Sci. Environ. Manage. Sept》;20111231;第15卷(第3期);第451页右栏第1段和图1 |
| Synthesis and biological evaluation of 1-cyano-2-aminobenzimidazole derivatives as a novel class of antitumor agents;Zhang Hu et al.,;《Med Chem Res》;20141231;第23卷;第3029-3038页 |
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