CN109516944B - Preparation method of 3-nitropyrrole - Google Patents

Preparation method of 3-nitropyrrole Download PDF

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CN109516944B
CN109516944B CN201811595687.2A CN201811595687A CN109516944B CN 109516944 B CN109516944 B CN 109516944B CN 201811595687 A CN201811595687 A CN 201811595687A CN 109516944 B CN109516944 B CN 109516944B
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nitropyrrole
pyrrole
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CN109516944A (en
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邹建平
陶泽坤
李成坤
达莫拉·苏布
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Suzhou University
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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
    • C07D207/34—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 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 to ring carbon atoms
    • C07D207/42—Nitro radicals

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyrrole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

The invention discloses a preparation method of 3-nitropyrrole. Pyrrole, sodium nitrite and peroxydisulfate are added into solvent to react at 60-120 deg.c to obtain 3-nitro pyrrole. The pyrrole is used as an initiator, raw materials are easy to obtain, and the prepared target product can be directly used or used for other further reactions. The invention takes sodium nitrite as a nitration reagent, is safe to use and low in price, reduces pollution and production cost, and meets the requirement of green production. The preparation method disclosed by the invention is mild in reaction condition, simple in reaction operation and post-treatment process, stable and controllable in reaction process, high in product yield and suitable for large-scale production.

Description

Preparation method of 3-nitropyrrole
Technical Field
The invention belongs to the technical field of preparation of organic compounds, and particularly relates to a preparation method of 3-nitropyrrole.
Background
Pyrrole and its derivatives are not only used in the synthesis of pharmaceuticals, but also as important synthetic intermediates for pesticides, fragrances, dyes and functional materials (ref.1: M. Zhang, X. Fang, H. Neumann et al, General and regenerative synthesis of pesticides, J. Am. chem. Soc. 2013, 135, 11384. multidot. 11388).
3-Nitropyrrole is an important pyrrole derivative and plays an important role as an alkaloid in The study of DNA (ref.2: D. Loakes, D.M. Brown, S. Linde et al, 3-Nitropyrelose and 5-noninductive as non-reactive bases in primers for DNA sequencing and PCR, Nucleic Acids Research, 1995, 23, 2361-. 3-nitropyrrole is also an important organic synthesis intermediate, and can be simply converted into important products, namely 3-aminopyrrole, 5H-pyrrolo [3,2-D ] pyrimidine and the like. In the existing preparation technology of 3-nitropyrrole, the defects of use of dangerous reagents (acyl chloride with strong irritation and nitric acid with strong oxidizing property), multiple reaction steps (3-4 steps) and low comprehensive yield exist; therefore, it is necessary to find a preparation method of the 3-nitropyrrole, which has mild reaction conditions and good universality and meets the requirement of green production.
Disclosure of Invention
The invention aims to provide a preparation method of 3-nitropyrrole, which has the advantages of no need of metal catalysis, no need of amino protection, convenient raw material source, simple reaction steps and the like.
In order to achieve the purpose of the invention, the technical scheme adopted by the invention is as follows:
a process for preparing 3-nitro pyrrole uses pyrrole and sodium nitrite as raw materials, and reacts in the presence of peroxodisulfate to prepare 3-nitro pyrrole.
In the above technical scheme, the reaction is carried out in the presence of a solvent; the solvent is selected from: acetonitrile, tetrahydrofuran, 1, 2-dichloroethane, dimethyl sulfoxide, toluene, chlorobenzene, N-dimethylformamide.
In the technical scheme, the reaction temperature is 60-120 ℃; the reaction was followed by thin layer chromatography until complete.
In the above technical scheme, the chemical formula of the peroxydisulfate is X2S2O8Wherein X is Na or NH4Or K.
In the technical scheme, after the reaction is finished, the product is subjected to column chromatography separation and purification treatment to obtain the 3-nitropyrrole; preferably, in the column chromatography separation and purification treatment, petroleum ether and ethyl acetate in a volume ratio of 4:1 are used as eluent.
The invention also discloses the application of the peroxydisulfate in the preparation of 3-nitropyrrole by taking pyrrole and sodium nitrite as raw materials; preferably, the peroxodisulfate salt has the formula X2S2O8Wherein X is Na or NH4Or K.
In the technical scheme, the preparation of the 3-nitropyrrole is carried out in a solvent, and the solvent is selected from: one of acetonitrile, tetrahydrofuran, 1, 2-dichloroethane, dimethyl sulfoxide, toluene, chlorobenzene and N, N-dimethylformamide; the temperature for preparing the 3-nitropyrrole is 60-120 ℃; and tracking the reaction by using thin-layer chromatography (TLC) until the reaction is completely finished, and performing column chromatography separation and purification treatment on the product after the reaction is finished to obtain the 3-nitropyrrole.
In the present invention, the pyrrole is represented by the following chemical structural formula:
Figure 69073DEST_PATH_IMAGE001
the 3-nitropyrrole is shown as the following chemical structural formula:
Figure 152305DEST_PATH_IMAGE002
due to the application of the technical scheme, compared with the prior art, the invention has the following advantages:
1. the invention does not use metal reagent, is suitable for the drug production process, and the target product is obtained by heating in the solvent;
2. the method takes sodium nitrite as a nitration reagent, is safe to use and low in price, reduces pollution and production cost, and meets the requirement of green production;
3. the pyrrole is used as an initiator, amino groups do not need to be protected, and a product can be obtained through one-step reaction;
4. the preparation method disclosed by the invention has the advantages of mild reaction conditions, simple reaction operation and post-treatment process, stable and controllable reaction process, high product yield and suitability for mass production.
Detailed Description
The preparation of the 3-nitropyrroles of the present invention is further described below with reference to the examples:
example one
Pyrrole is used as a raw material, and the reaction steps are as follows:
Figure 165260DEST_PATH_IMAGE003
pyrrole (0.7 g, 10 mmol), sodium nitrite (1.4 g, 20 mmol), potassium peroxodisulfate (2.7 g, 10 mmol) and acetonitrile (50 ml) were added to a reaction flask and reacted at 60 ℃;
Figure 860815DEST_PATH_IMAGE004
TLC tracing the reaction until the reaction is completely finished;
Figure 275615DEST_PATH_IMAGE005
the crude product obtained after the completion of the reaction was separated by column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain the objective product (yield 95%). Analytical data for the product are as follows:1H NMR (400 MHz, DMSO-d 6):11.56 (s, 1H),10.64 (s, 1H), 7.20 (dd,J= 5.8, 1.3Hz, 1H), 6.36 (dd,J= 5.8, 1.4Hz, 1H)。
example two
Pyrrole is used as a raw material, and the reaction steps are as follows:
Figure 529748DEST_PATH_IMAGE003
pyrrole (0.7 g, 10 mmol), sodium nitrite (2.1 g, 30 mmol), sodium peroxodisulfate (2.379 g, 10 mmol) and tetrahydrofuran (50 ml) were added to a reaction flask and reacted at 60 ℃;
Figure 30000DEST_PATH_IMAGE004
TLC tracing the reaction until the reaction is completely finished;
Figure 263666DEST_PATH_IMAGE005
the crude product obtained after the completion of the reaction was separated by column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain the objective product (yield 98%).
EXAMPLE III
Pyrrole is used as a raw material, and the reaction steps are as follows:
Figure 798552DEST_PATH_IMAGE003
pyrrole (0.7 g, 10 mmol), sodium nitrite (1.4 g, 20 mmol), ammonium peroxodisulfate (2.279 g, 10 mmol) and 1, 2-dichloroethane (50 ml) were added to a reaction flask and reacted at 70 ℃;
Figure 912002DEST_PATH_IMAGE004
TLC tracing the reaction until the reaction is completely finished;
Figure 142958DEST_PATH_IMAGE005
the crude product obtained after the completion of the reaction was separated by column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain the objective product (yield 96%).
Example four
Pyrrole is used as a raw material, and the reaction steps are as follows:
Figure 429583DEST_PATH_IMAGE003
pyrrole (0.7 g, 10 mmol), sodium nitrite (0.7 g, 10 mmol), sodium peroxodisulfate (2.379 g, 10 mmol) and dimethyl sulfoxide (50 ml) were added into a reaction flask and reacted at 120 ℃;
Figure 304129DEST_PATH_IMAGE004
TLC tracing the reaction until the reaction is completely finished;
Figure 588480DEST_PATH_IMAGE005
the crude product obtained after the completion of the reaction was separated by column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain the objective product (yield 92%).
EXAMPLE five
Pyrrole is used as a raw material, and the reaction steps are as follows:
Figure 63323DEST_PATH_IMAGE003
pyrrole (0.7 g, 10 mmol), sodium nitrite (0.7 g, 10 mmol), ammonium peroxodisulfate (2.279 g, 10 mmol) and toluene (50 ml) were added to a reaction flask and reacted at 90 ℃;
Figure 402907DEST_PATH_IMAGE004
TLC tracing the reaction until the reaction is completely finished;
Figure 646806DEST_PATH_IMAGE005
the crude product obtained after the reaction is separated by column chromatography(petroleum ether: ethyl acetate = 4:1) to obtain the objective product (yield 93%).
EXAMPLE six
Pyrrole is used as a raw material, and the reaction steps are as follows:
Figure 836479DEST_PATH_IMAGE003
pyrrole (0.7 g, 10 mmol), sodium nitrite (1.4 g, 20 mmol), potassium peroxodisulfate (2.7 g, 10 mmol) and chlorobenzene (50 ml) were added to a reaction flask and reacted at 100 ℃;
Figure 549351DEST_PATH_IMAGE004
TLC tracing the reaction until the reaction is completely finished;
Figure 177779DEST_PATH_IMAGE005
the crude product obtained after the completion of the reaction was separated by column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain the objective product (yield 95%).
EXAMPLE seven
Pyrrole is used as a raw material, and the reaction steps are as follows:
Figure 791032DEST_PATH_IMAGE003
pyrrole (0.7 g, 10 mmol), sodium nitrite (0.7 g, 10 mmol), ammonium peroxodisulfate (2.279 g, 10 mmol) and N, N-dimethylformamide (50 ml) were added to a reaction flask and reacted at 110 ℃;
Figure 151606DEST_PATH_IMAGE004
TLC tracing the reaction until the reaction is completely finished;
Figure 601042DEST_PATH_IMAGE006
the crude product obtained after the completion of the reaction was separated by column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain the objective product (yield 92%).

Claims (5)

1. The preparation method of the 3-nitropyrrole is characterized in that pyrrole and sodium nitrite are used as raw materials, and the 3-nitropyrrole is prepared through reaction in the presence of peroxydisulfate, wherein the reaction temperature is 60-120 ℃; the chemical formula of the peroxydisulfate is X2S2O8Wherein X is NH4Or K.
2. The process for producing 3-nitropyrrole according to claim 1, wherein the reaction is carried out in the presence of a solvent.
3. The process for the preparation of 3-nitropyrroles according to claim 2, characterized in that said solvent is selected from: acetonitrile, tetrahydrofuran, 1, 2-dichloroethane, dimethyl sulfoxide, toluene, chlorobenzene, N-dimethylformamide.
4. The process for the preparation of 3-nitropyrroles according to claim 1, characterized in that the reaction is followed by thin layer chromatography until complete completion.
5. The preparation method of 3-nitropyrrole according to claim 1, characterized in that, after the reaction is finished, the product is subjected to column chromatography separation and purification treatment to obtain 3-nitropyrrole.
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