CN107935927A - A kind of synthesis of the more yuan of rings of benzo-aza - Google Patents
A kind of synthesis of the more yuan of rings of benzo-aza Download PDFInfo
- Publication number
- CN107935927A CN107935927A CN201711248621.1A CN201711248621A CN107935927A CN 107935927 A CN107935927 A CN 107935927A CN 201711248621 A CN201711248621 A CN 201711248621A CN 107935927 A CN107935927 A CN 107935927A
- Authority
- CN
- China
- Prior art keywords
- benzo
- aza
- yuan
- rings
- synthesis
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
- C07D223/22—Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines
- C07D223/30—Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines with hetero atoms directly attached to the ring nitrogen atom
-
- 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
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
- C07D223/22—Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines
- C07D223/24—Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines with hydrocarbon radicals, substituted by nitrogen atoms, attached to the ring nitrogen atom
- C07D223/28—Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines with hydrocarbon radicals, substituted by nitrogen atoms, attached to the ring nitrogen atom having a single bond between positions 10 and 11
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of synthetic method of the more yuan of rings of benzo-aza, structure of the more yuan of rings of benzo-aza shown in just like formula A, the synthetic method of the more yuan of rings of the benzo-aza are illustrated with the example that synthesizes of benzo-aza compounds with 7-member cycle 3 and benzo-aza 5-membered ring compounds 5.The solution have the advantages that：First, the synthesis of the more yuan of rings of benzo-aza is realized, this method has broad application prospects in organic synthesis and pharmaceutical synthesis field；Secondly, the method is easy to operate, can be applicable in the Fast back-projection algorithm with 5,6,7 yuan of rings of benzo-aza.
Description
Technical field
The invention belongs to the technical field of organic chemistry, and in particular to it is a kind of by occur on 1,2-, bis- benzynes nucleophilic with
The cascade process of Ene reactions obtains the method for benzo-aza multicyclic compound.
Background technology
With organic chemistry and pharmaceutical chemical development, it has been found that benzo-aza more ring structures widely exist in day
In right product and drug molecule.Therefore, a series of a kind of more membered ring skeletons of benzo-azas of structure that can be rapidly and efficiently are developed
Method, have great significance in the research of organic chemistry.Aryne intermediates can easily occur because of its high activity
Nucleophilic and all cyclizations, and then rapidly build Multi substituted benzenes structure.Therefore, the chemical conversion that benzyne participates in is in natural products
With being had a wide range of applications in pharmaceutical synthesis.
In recent years, a kind of new domino aryne precursor is reported out, it can pass through a step domino cascade process
Successively continuously receive 1,2,3- continuous three officials of two nucleophilic atoms and an electrophilic atoms at suitable temperatures phenyl ring on 1,2,3- position
Energyization.The present invention utilizes this new domino aryne precursor, and the necleophilic reaction of benzyne and Ene reaction bondeds are got up, first
Necleophilic reaction occurred for nitrogen-atoms and first aryne of generation before this, and with alkene ene occurs for the aryne of following second generation
Reaction, is successfully realized benzo-aza five, six, the structure of heptatomic ring.To synthesize drug molecule or day with this class formation
Right product provides a kind of method rapidly and efficiently.
Embodiment
With reference to embodiment, the invention will be further described：
The benzo-aza multicyclic compound structural formula A of the present invention is as follows：
Embodiment
Two embodiments are set forth below, and the present invention will be further described
1. the synthesis of benzo-aza compounds with 7-member cycle 3：
By structural formula 1 (94.5mg, 0.3mmol, 1.0equiv.), cesium fluoride (CsF) (182.28mg, 1.2mmol,
4.0equiv.) and cesium carbonate (Cs2CO3) (195.6mg, 0.6mmol, 2.0equiv.) is dissolved in acetonitrile (MeCN) (30mL),
0.5h is stirred under the conditions of 80 DEG C, then structural formula 2 (267.8mg, 0.6mmol, 2.0equiv.) is dissolved in acetonitrile (MeCN) (10ml)
In, and added with slow syringe pump 8h in this reaction system.Question response is complete, and acetonitrile is removed, and crude reaction is directly through silica gel
Column chromatography purifies, and obtains the benzo-aza compounds with 7-member cycle product of 47.0 milligrams of structural formulas 3, yield 41%.
The physical property and characterize data of resulting structures formula 3:
Fusing point (Mp):137-139℃；1H NMR (500MHz, CDCl3) δ 7.63 (d, J=10.0Hz, 1H), 7.58-
7.52 (m, 3H), 7.41 (d, J=9.0Hz, 1H), 7.23-7.11 (m, 11H), 7.05 (d, J=8.0Hz, 1H), 4.92 (s,
0.5H), 4.88 (s, 1H), 4.83 (s, 1H), 4.58 (s, 0.5H), 3.72 (d, J=12.5Hz, 0.5H), 3.52 (dd, J=
16.5,17.0Hz, 1H), 3.27 (t, J=16.5Hz, 1H), 3.15 (dd, J=20.0,20.0Hz, 0.5H), 2.66 (dd, J=
20.0,20.0Hz, 0.5H), 2.42 (d, J=6.0Hz, 1H), 2.39 (s, 3H), 2.38 (s, 1.5H), 1.45 (s, 3H), 1.37
(s,1.5H)ppm.13C NMR(125MHz,CDCl3)δ149.3,146.9,143.8,143.8,141.6,139.9,139.7,
138.6,138.4,138.0,137.8,136.4,136.0,132.1,131.4,129.8,129.7,129.5,129.3,
129.1,128.9,128.9,128.6,127.9,127.9,127.8,127.7,127.5,127.2,127.1,126.8,
113.2,112.9,51.5,44.6,35.9,35.5,22.6,21.7,18.5ppm；IR(thin film)3341,3072,
2938,2888,1642,1597,1484,1449,1344,1279,1246,1094,900,751,584,542,514cm-1；
HRMS-MALDI(m/z)calcd for[C24H23NNaO2S]+,412.1342；found,412.1343.
The compound of structure above 1 is known compound, its synthetic reaction referring to：
“Aerobic Intramolecular Oxidative Amination of Alkenes Catalyzed by
(the intramolecular olefin oxidation ammonification of NHC- coupling palladium species catalysis is anti-by NHC-Coordinated Palladium Complexes "
Should), Michelle M.Rogers, Johanna E.Wendlandt, IliaA.Guzei, and Shannon
S.Stahl.Org.Lett.,2006,8,2257-2260。
The compound of structure above 2 is known compound, its synthetic reaction referring to：
“Domino Aryne Precursor:Efficient Construction of 2,4-Disubstituted
Benzothiazoles " (domino aryne precursors：Efficiently structure 2,4- bis- substitutes this simultaneously thiazole), Jiarong Shi,
Dachuan Qiu,Juan Wang,Hai Xu,Yang Li*.J.Am.Chem.Soc.,2015,137(17),5670–5673。
2. the synthesis of benzo-aza 5-membered ring compounds 5：
By structural formula 4 (71.0mg, 0.3mmol, 1.0equiv.), cesium fluoride (CsF) (182.28mg, 1.2mmol,
4.0equiv.) and cesium carbonate (Cs2CO3) (195.6mg, 0.6mmol, 2.0equiv.) is dissolved in acetonitrile (MeCN) (30mL),
0.5h is stirred under the conditions of 80 DEG C, then structural formula 2 (267.8mg, 0.6mmol, 2.0equiv.) is dissolved in acetonitrile (MeCN) (10ml)
In, and added with slow syringe pump 8h in this reaction system.Question response is complete, and acetonitrile is removed, and crude reaction is directly through silica gel
Column chromatography purifies, and obtains the benzo-aza compounds with 7-member cycle product of 40.0 milligrams of structural formulas 5, yield 42%.
The physical property and characterize data of resulting structures formula 5:
1H NMR(500MHz,CDCl3)δ7.70-7.66(m,3H),7.23-7.21(m,3H),7.00–6.96(m,2H),
4.77-4.76 (m, 1H), 4.72 (s, 1H), 4.04 (t, J=10.3Hz, 1H), 3.87-3.83 (m, 1H), 3.71-3.67 (m,
1H),2.37(s,3H),1.39(s,3H).ppm；13C NMR(125Hz,CDCl3)δ143.3,143.2,141.4,133.0,
132.3,128.8,127.5,126.6,124.4,122.9,113.9,113.0,53.4,47.2,20.7,17.6.ppm；IR
(thin film)3446,2923,1590,1454,1358,1301,1166,1131,1092,1048,968,813,753,720,
664,577,cm-1；HRMS-MALDI(m/z)calcd for[C18H19NNaO2S]+,336.1029；found,336.1031.
The compound of structure above 4 is known compound, its synthetic reaction referring to：
“Palladium-Catalyzed Intermolecular Oxidative Cyclization of
Allyltosylamides withAcOH:Assembly of3-Pyrrolin-2-ones " (the cyclopropylene acid amides of palladium chtalyst with
The intermolecular oxidative cyclization of acetic acid：The preparation of 3- pyrroles's -2- ketone), Jiuzhong Huang, Jia Zheng, Wanqing Wu,
Jianxiao Li,Zhiqiang Ma*,Yanwei Ren,and Huanfeng Jiang*J.Org.Chem.,2017,82
(15),8191–8198
Obtain one and be mentioned that the benzo-aza multicyclic compound obtained using this method is widely existed as nuclear structure
In the structure of natural products and drug molecule, for example, meter Pa Ming, Sunitinib, strychnia.The synthetic method is for synthesis
Natural products or drug molecule with such core skeleton provide a synthetic route rapidly and efficiently, have important reality
With value.
Brief description of the drawings：
Fig. 1 is benzo-aza more ring structures general formula of the present invention
Fig. 2 is the synthesis of benzo-aza compounds with 7-member cycle 3
Fig. 3 is the synthesis of benzo-aza 5-membered ring compounds 5
Fig. 4 is that the natural products of benzo-aza multicyclic compound is illustrated
The medicine used：
Claims (2)
1. a kind of synthesis of the more yuan of rings of benzo-aza, its structural formula are as follows：
2. the polynary ring synthetic method of benzo-aza according to claim 1, it is characterized in that, comprise the following steps：
The alkenes compounds that N- p-toluenesulfonyls are protected, cesium fluoride and cesium carbonate are dissolved in acetonitrile, under the conditions of 80 DEG C
0.5h is stirred, then domino aryne precursor is dissolved in acetonitrile, and is added with slow syringe pump 8h in this reaction system.Question response
Completely, acetonitrile is removed, crude reaction is directly purified through silica gel column chromatography, obtains the production of sterling benzo-aza multicyclic compound
Thing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711248621.1A CN107935927A (en) | 2017-12-01 | 2017-12-01 | A kind of synthesis of the more yuan of rings of benzo-aza |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711248621.1A CN107935927A (en) | 2017-12-01 | 2017-12-01 | A kind of synthesis of the more yuan of rings of benzo-aza |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107935927A true CN107935927A (en) | 2018-04-20 |
Family
ID=61948292
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711248621.1A Pending CN107935927A (en) | 2017-12-01 | 2017-12-01 | A kind of synthesis of the more yuan of rings of benzo-aza |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107935927A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104829553A (en) * | 2015-03-16 | 2015-08-12 | 重庆大学 | New method of synthesizing 2,4-di-substituted benzothiazole |
| CN105820137A (en) * | 2016-03-25 | 2016-08-03 | 重庆大学 | Novel method for synthesizing ortho diamido aromatic hydrocarbon through domino aryne precursor |
-
2017
- 2017-12-01 CN CN201711248621.1A patent/CN107935927A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104829553A (en) * | 2015-03-16 | 2015-08-12 | 重庆大学 | New method of synthesizing 2,4-di-substituted benzothiazole |
| CN105820137A (en) * | 2016-03-25 | 2016-08-03 | 重庆大学 | Novel method for synthesizing ortho diamido aromatic hydrocarbon through domino aryne precursor |
Non-Patent Citations (1)
| Title |
|---|
| RAVINDRA D. AHER，等: "Diastereoselective Synthesis of Chiral 2,3-Disubstituted Indolines via Formal [3+2]-Cycloaddition of Arynes with γ‑Amino-α,β-unsaturated Esters", 《JOURNAL OF ORGANIC CHEMISTRY》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wang et al. | Radical monofluoroalkylative alkynylation of olefins by a docking–migration strategy | |
| Zhu et al. | Visible-light-mediated direct difluoromethylation of alkynoates: synthesis of 3-difluoromethylated coumarins | |
| Wang et al. | Access to Chiral Hydropyrimidines through Palladium‐Catalyzed Asymmetric Allylic C− H Amination | |
| Yang et al. | Synthesis of Allenyl Sulfones via a TBHP/TBAI-Mediated Reaction of Propargyl Alcohols with Sulfonyl Hydrazides | |
| Han et al. | Lewis acid catalyzed [4+ 3] cycloaddition of propargylic alcohols with azides | |
| Yu et al. | Silver‐Mediated Oxidative Fluorotrifluoromethylation of Unactivated Alkenes | |
| Gu et al. | Pd-Catalyzed Intramolecular Heck Reaction, C (sp2)–H Activation, 1, 4-Pd Migration, and Aminopalladation: Chemoselective Synthesis of Dihydroindeno [1, 2, 3-kl] acridines and 3-Arylindoles | |
| Wu et al. | Visible light-driven azidation/difunctionalization of vinyl arenes with azidobenziodoxole under copper catalysis | |
| Zhang et al. | TBHP/KI-promoted annulation of anilines, ethers, and elemental sulfur: access to 2-Aryl-, 2-heteroaryl-, or 2-alkyl-substituted benzothiazoles | |
| Zhu et al. | Transition-metal-free diastereoselective epoxidation of trifluoromethylketones with N-tosylhydrazones: access to tetrasubstituted trifluoromethylated oxiranes | |
| Liang et al. | Atom‐Economic Silver‐Catalyzed Difunctionalization of the Isocyano Group with Cyclic Oximes: Towards Pyrimidinediones | |
| Ma et al. | Copper-catalyzed fluoroalkylation of alkynes, and alkynyl & vinyl carboxylic acids with fluoroalkyl halides | |
| CN103113308B (en) | Method for preparing dihydropyrimidinone derivative | |
| Zhang et al. | Synthesis of α-methylene-β-lactams enabled by base-promoted intramolecular 1, 2-addition of N-propiolamide and C–C bond migrating cleavage of aziridine | |
| Taily et al. | Arylcyclopropane yet in its infancy: the challenges and recent advances in its functionalization | |
| Wang et al. | Nitrosoarenes as Nitrogen Source for Generation of Sulfonamides with the Insertion of Sulfur Dioxide under Metal‐Free Conditions | |
| Nguyen et al. | Sulfur-promoted DABCO-catalyzed oxidative trimerization of phenylacetonitriles | |
| Jian et al. | Construction of 9-functionalized xanthenes via Diels-Alder reaction of stable ortho-quinone methides and arynes | |
| Ma et al. | One-pot synthesis of iodo-dibenzothiazines from 2-biaryl sulfides | |
| Liu et al. | A copper-catalyzed three-component reaction of alkenes, cycloketone oximes and DABCO·(SO2) 2: Direct C (sp2)-H cyanoalkylsulfonylation | |
| Xian et al. | Enantioselective synthesis of fused dihydropyranones via squaramide-catalyzed Michael addition/lactonization cascade reaction | |
| Rajale et al. | An efficient synthesis of 4-substituted coumarin derivatives via a palladium-catalyzed Suzuki cross-coupling reaction | |
| Zhang et al. | A facile access to thieno [2, 3-b] indoles via sulfur-mediated decarboxylative cyclization of α, β-unsaturated carboxylic acids with indoles | |
| Hu et al. | NIS-mediated ring-closure/opening cascade reactions of allylamides: an expedient route to oxazolines | |
| CN107935927A (en) | A kind of synthesis of the more yuan of rings of benzo-aza |
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 | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20180420 |
|
| WD01 | Invention patent application deemed withdrawn after publication |