CN104844496A - Catalytic synthesized beta-nitropyrrole derivative and synthetic method thereof - Google Patents
Catalytic synthesized beta-nitropyrrole derivative and synthetic method thereof Download PDFInfo
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- CN104844496A CN104844496A CN201510185584.9A CN201510185584A CN104844496A CN 104844496 A CN104844496 A CN 104844496A CN 201510185584 A CN201510185584 A CN 201510185584A CN 104844496 A CN104844496 A CN 104844496A
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- nitro
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- pyrrole
- pyrroles
- phenyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
Abstract
The invention relates to a catalytic synthesized beta-nitropyrrole derivative and a synthetic method thereof, a general formula of the catalytic synthesized beta-nitropyrrole derivative is shown as follows. The preparation method comprises the following steps: a solution of a chiral trimetal Pd/Sm/Pd complex catalyst is performed with in-situ preparation in a solvent, a pyrroles compound and a nitro olefines compound are added while stirring, and a mixture is separated by a column chromatography to obtain a pure product which is the beta-nitro pyrroles derivative. The method has the advantage that trimetal complex is taken as a catalyst for synthesizing the beta-nitro pyrroles derivative, and the method has the advantages of convenient preparation, low price, high yield and realization of large-batch synthesis.
Description
Technical field
The present invention relates to the synthetic method field of optical purity β-nitro-pyrrole compounds, particularly relate to a kind of method by three metal complex catalyzed synthesizing optical pure β-nitro-pyrrole derivatives.
Background technology
The reaction of asymmetric Friedel-Crafts is the linked reaction of the important C-C of a class.Pyrrole ring is the important feature unit of many natural products and medicine.But because pyrroles is relatively unstable under sour environment, so less for the asymmetric alkylation research of pyrrole ring.The present invention reports under the environment without the need to protection, pyrroles and the reaction of nitroolefin generation Friedel-Crafts.
Summary of the invention
The object of the invention is to provide easy and simple to handle, reaction temperature and, cost is low, yield is high stereoselectivity catalyzes and synthesizes a kind of optical purity β-nitro-pyrrole derivative and synthetic method
Method.
A kind of optical purity β-nitro-pyrrole derivative, its general formula (I) is:
Wherein, R represents hydrogen or ethyl, and R ' represents phenyl, substituted-phenyl, heterocyclic radical or substituted heterocyclic radical.Preparation method comprises the following steps: the solution first preparing three metal complex catalysts in tetrahydrofuran solvent, azoles and nitroolefin compounds is added under stirring, thereafter room temperature reaction 65 hours, after reaction terminates, gained mixture obtains sterling by pillar layer separation, is β-nitro-pyrrole derivative.
Described polar solvent is: tetrahydrofuran (THF) or ethanol.
Described pyrroles is: pyrroles or N-ethyl pyrrole N-.
Described replacement nitroolefin (containing R ') can be phenyl, substituted-phenyl, heterocyclic radical or substituted heterocyclic radical.
Described pyrroles and the molar ratio of nitroolefin are 3:1.
Described pyrroles and nitroolefin derivatives reaction temperature are room temperature, and the reaction times is 65 hours.
Advantage of the present invention is: utilize three metal complexess as catalyzer, synthesis β-nitro-pyrrole derivative, easy to prepare, price is lower, yield is high, can synthesize in enormous quantities, is applicable to industrial production application.Be widely used for asymmetric Friedel-Crafts reaction efficiency is high, can be used for the starting material preparing multi-medicament intermediate.
Embodiment
A kind of synthetic method catalyzing and synthesizing optical purity β-nitro-pyrrole derivative, comprise: the solution first preparing three metal complex catalysts in tetrahydrofuran solvent, azoles and nitroolefin compounds is added under stirring, thereafter room temperature reaction 65 hours, after reaction terminates, gained mixture obtains sterling by pillar layer separation, is β-nitro-pyrrole derivative.Wherein: the molar ratio of pyrroles and nitroolefin is 3:1.
Below in conjunction with specific embodiment, the invention will be further described.
The general formula of the asymmetry catalysis Friedel-Crafts reaction in the embodiment of the present invention is as follows:
embodiment 1:2-(2-nitro-1-styroyl) synthesis of-1H-pyrroles
the solution of preparation chirality three metal Pds/Sm/Pd composition catalyst: to containing in the 0.4ml THF solution of part (4.15mg, 0.01mmol) of stirring, in batches add solid Pd (OAc) under room temperature
2(2.24 mg, 0.01 mmol), mixture stirs 15min, obtains yellow suspension, adds Sm (OTf) in batches
3(2.99 mg, 0.005 mmol), yellow suspension is yellowing transparent liquid immediately, continues stirring 15 min under room temperature, obtains the solution of chirality three metal Pds/Sm/Pd composition catalyst.
In above-mentioned catalyst solution, add 1H-pyrroles (0.60 mmol) and 2-nitrostyrolene (0.20 mmol) successively, at room temperature stir 65h, after reaction terminates, gained mixture obtains sterling by pillar layer separation, yellow solid,
1h NMR (400 MHz, CDCl
3): δ 7.84 (bs, 1H), 7.38-7.29 (m, 3H), 7.25-7.23 (m, 2H), 6.70-6.68 (m, 1H), 6.18-6.16 (m, 1H), 6.10-6.08 (m, 1H), 4.99 (dd
j=12.0,7.2 Hz, 1H), 4.92-4.89 (m, 1H), 4.81 (dd,
j=12.0,7.6 Hz, 1H);
13c NMR (101 MHz, CDCl
3): δ 138.4,129.6,129.3,128.6,128.3,118.6,109.1,106.2,79.6,43.3. 85% ee; [α]
d 20+ 58.8 (c=1.1, CH
2cl
2).
Described part is one of following:
the synthesis of embodiment 2:2-[1-(4-bromophenyl)-2-nitro-ethyl]-5-ethyl-1H-pyrroles
To containing in the 0.4ml THF solution of part (4.15mg, 0.01mmol) of stirring, under room temperature, add solid Pd (OAc) in batches
2(2.24 mg, 0.01 mmol), mixture stirs 15min, obtains yellow suspension, adds Sm (OTf) in batches
3(2.99 mg, 0.005 mmol), yellow suspension is yellowing transparent liquid immediately.Stirring 15 min is continued under room temperature, obtain catalyst solution, 2-ethyl-1H-pyrroles (0.60 mmol) and the bromo-2-nitrostyrolene of 4-(0.20 mmol) is added successively in this solution, at room temperature stir 65h, after reaction terminates, gained mixture obtains sterling by pillar layer separation, brown oil (58.0 mg, 90%).
1h NMR (400 MHz, CDCl
3): δ 7.54 (bs, 1H), 7.50 (d,
j=8.0 Hz, 2H), 7.14 (d,
j=8.0 Hz, 2H), 5.96 (t,
j=4.0 Hz, 1H), 5.86 (t,
j=4.0 Hz, 1H), 4.97 (dd,
j=12.0,4.0 Hz, 1H), 4.83 (t,
j=8.0 Hz, 1H), 4.76 (dd,
j=12.0,8.0 Hz, 1H), 2.55 (q,
j=8.0 Hz, 2H), 1.21 (t,
j=8.0 Hz, 3H);
13c NMR (101 MHz, CDCl
3): δ 137.8,135.6,132.7,130.0,127.0,122.5,106.3,104.9,79.4,42.9,25.8,21.1,13.8,50% ee; [α]
d 20+ 11.6 (c=0.6, CH
2cl
2).
Claims (6)
1. optical purity β-nitro-pyrrole analog derivative, is characterized in that its general formula is:
Wherein, R represents hydrogen or ethyl, and R ' represents phenyl, substituted-phenyl, heterocyclic radical or substituted heterocyclic radical.
2. optical purity β-nitro-pyrrole analog derivative according to claim 1, is characterized in that preparation method comprises the following steps:
First original position prepares the solution of chirality three metal Pds/Sm/Pd composition catalyst in a solvent, azoles and nitroolefin compounds is added under stirring, thereafter room temperature reaction 63-67 hour, after reaction terminates, gained mixture obtains sterling by pillar layer separation, is β-nitro-pyrrole derivative.
3. β according to claim 2-nitro-pyrrole derivative, is characterized in that: described pyrroles and the molar ratio of nitroolefin are 3:1.
4. β according to claim 2-nitro-pyrrole derivative, is characterised in that described solvent is: tetrahydrofuran (THF) or ethanol.
5. β according to claim 2-nitro-pyrrole derivative, is characterized in that: described pyrroles is: pyrroles or N-ethyl pyrrole N-.
6. β according to claim 2-nitro-pyrrole derivative, is characterised in that described nitroolefin can be phenyl, substituted-phenyl, heterocyclic radical or substituted heterocyclic radical.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111196778A (en) * | 2020-01-14 | 2020-05-26 | 郑州轻工业大学 | Synthetic method of 3-ethylamino pyrrole compound |
Citations (3)
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|---|---|---|---|---|
| CN101239939A (en) * | 2007-02-06 | 2008-08-13 | 北京大学 | Chirality five-membered heterocyclic compound and high enantioselectivity preparation method thereof |
| CN101486673A (en) * | 2009-02-11 | 2009-07-22 | 中国科学院上海有机化学研究所 | Optical activity 2-(2-nitro-ethyl)-pyrrole, synthetic method and use |
| JP2011006363A (en) * | 2009-06-26 | 2011-01-13 | Chiba Univ | Tetrahydropyridine derivative and method for producing the same |
-
2015
- 2015-04-20 CN CN201510185584.9A patent/CN104844496A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101239939A (en) * | 2007-02-06 | 2008-08-13 | 北京大学 | Chirality five-membered heterocyclic compound and high enantioselectivity preparation method thereof |
| CN101486673A (en) * | 2009-02-11 | 2009-07-22 | 中国科学院上海有机化学研究所 | Optical activity 2-(2-nitro-ethyl)-pyrrole, synthetic method and use |
| JP2011006363A (en) * | 2009-06-26 | 2011-01-13 | Chiba Univ | Tetrahydropyridine derivative and method for producing the same |
Non-Patent Citations (1)
| Title |
|---|
| GUOQI ZHANG: "A heterotrimetallic Pd–Sm–Pd complex for asymmetric Friedel–Crafts alkylations of pyrroles with nitroalkenes", 《ORGANIC & BIOMOLECULAR CHEMISTRY》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111196778A (en) * | 2020-01-14 | 2020-05-26 | 郑州轻工业大学 | Synthetic method of 3-ethylamino pyrrole compound |
| CN111196778B (en) * | 2020-01-14 | 2022-08-19 | 郑州轻工业大学 | Synthetic method of 3-ethylamino pyrrole compound |
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Application publication date: 20150819 |