CN110372697A - Using DMF and ammonium iodide as the new method of cyanylation agent building 2- phenylimidazole [1,2-a] pyridine -3- nitrile - Google Patents
Using DMF and ammonium iodide as the new method of cyanylation agent building 2- phenylimidazole [1,2-a] pyridine -3- nitrile Download PDFInfo
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- CN110372697A CN110372697A CN201910713629.3A CN201910713629A CN110372697A CN 110372697 A CN110372697 A CN 110372697A CN 201910713629 A CN201910713629 A CN 201910713629A CN 110372697 A CN110372697 A CN 110372697A
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- phenylimidazole
- pyridine
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- ammonium iodide
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- 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
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Abstract
The invention discloses one kind using DMF (N,N-dimethylformamide) and ammonium iodide as the new method of one step of cyanylation agent building 2- phenylimidazole [1,2-a] pyridine -3- nitrile.This method, as reaction raw materials, constructs 2- phenylimidazole [1,2-a] pyridine -3- nitrile using DMF (n,N-Dimethylformamide) and ammonium iodide as one step of cyanylation agent with 2- phenylimidazole [1,2-a] pyridine.The method of the present invention synthesizing mean is novel, reaction condition is mild, reaction reagent is cheap and easy to get, N, dinethylformamide not only can be used as reaction dissolvent but also can be used as the carbon atom in cyanylation agent offer cyano, and ammonium iodide then provides the nitrogen-atoms in cyano, such combination cyanogen source is safe and non-toxic, meets the demand for development of Green Chemistry.
Description
Technical field
The invention belongs to the technical fields such as medicine, material, cell biology, and in particular to one kind with DMF (N, N- diformazan
Base formamide) and ammonium iodide as one step of cyanylation agent building 2- phenylimidazole [1,2-a] pyridine -3- nitrile new method.
Background technique
2- phenylimidazole [1,2-a] pyridine -3- nitrile compounds are a kind of very important pharmaceutical intermediates, can be used for closing
At the various drug molecules with pharmaceutical activity, the structural framework for being included using such compound can construct me as starting material
Known to drug molecule grains of sand pyrrole denier with antidepressant effect and have anesthesiophore Necopidem.Traditional is cyanalation
Reagent, such as Cymag, potassium cyanide, copper cyanider and zinc cyanide often generate the cyaniding of severe toxicity in cyanalation process
Hydrogen other, cause serious environmental pollution, while keeping last handling process extremely inconvenient, there are very big security risks.Such
Under research background, we have proposed one kind using DMF (n,N-Dimethylformamide) and ammonium iodide as one step of cyanylation agent
The new method of 2- phenylimidazole [1,2-a] pyridine -3- nitrile is constructed, this method is with DMF (n,N-Dimethylformamide) and ammonium iodide
Cyanalation reaction is realized as combination cyanogen source, wherein the carbon atom in DMF (n,N-Dimethylformamide) offer cyano, and iodate
Ammonium then provides the nitrogen-atoms in cyano, such cyanalation reaction avoids the generation of hypertoxic gas cyaniding hydrogen, safe and non-toxic, meets
The demand for development of Green Chemistry.Its synthetic route is as follows:
2- phenylimidazole [1,2-a] pyridine -3- nitrile that the present invention synthesizes, structural formula are as follows:
The invention constructs 2- phenylimidazole using DMF (N,N-dimethylformamide) and ammonium iodide as one step of cyanylation agent
[1,2-a] pyridine -3- nitrile provides a novel synthetic route for the synthesis of such compound.The invention synthesizing mean is new
Grain husk, reaction condition is mild, and reaction reagent is cheap and easy to get, and n,N-Dimethylformamide not only can be used as reaction dissolvent but also can be used as
Cyanylation agent provides the carbon atom in cyano, and ammonium iodide then provides the nitrogen-atoms in cyano, such combination cyanogen source safety nothing
Poison meets the demand for development of Green Chemistry.
Summary of the invention
The present invention relates to one kind to construct 2- using DMF (N,N-dimethylformamide) and ammonium iodide as one step of cyanylation agent
The new method of phenylimidazole [1,2-a] pyridine -3- nitrile.This method with 2- phenylimidazole [1,2-a] pyridine as reaction raw materials, with
DMF (N,N-dimethylformamide) and ammonium iodide are as one step of cyanylation agent building 2- phenylimidazole [1,2-a] pyridine -3-
Nitrile.The method of the present invention synthesizing mean is novel, and reaction condition is mild, and reaction reagent is cheap and easy to get, and n,N-Dimethylformamide both may be used
Can be used as the carbon atom in cyanylation agent offer cyano again as reaction dissolvent, and ammonium iodide then provides the nitrogen in cyano
Atom, such combination cyanogen source is safe and non-toxic, meets the demand for development of Green Chemistry.
Technical solution of the present invention is as follows.
One kind constructing 2- phenylimidazole using DMF (N,N-dimethylformamide) and ammonium iodide as one step of cyanylation agent
The new method of [1,2-a] pyridine -3- nitrile, synthetic route are as follows:
In the above method, 2- phenylimidazole [1, the 2-a] pyridine -3- nitrile is by compound 1 through one step system of cyanalation reaction
?；The compound 1 is 2- phenylimidazole [1,2-a] pyridine, the specific steps are as follows:
Take compound 1 (2- phenylimidazole [1,2-a] pyridine) to be placed in container, promotor and solvent be added, put on filled with
The balloon of oxygen gas is stirred to react 1-48 hours, is cooled to room temperature after reaction, removes balloon, reaction solution filtering, decompression
After solvent is evaporated off, crude product is obtained, obtains compound 2- phenylimidazole [1,2-a] pyridine -3- nitrile through column Chromatographic purification；
In the above method, the reaction vessel of the specific steps is teat glass；The promotor is Gerhardite；
The additive is acetic acid；The solvent is DMF (N,N-dimethylformamide).
The amount and compound 1 (2- phenylimidazole [1,2-a] pyridine) of mantoquita are added in the above method, in the specific steps
Molar ratio be 2:1.
The amount and (2- phenylimidazole [1, the 2-a] pyrrole of compound 1 of additive are added in the above method, in the specific steps
Pyridine) molar ratio be 2:1.
The amount and (2- phenylimidazole [1, the 2-a] pyrrole of compound 1 of ammonium iodide are added in the above method, in the specific steps
Pyridine) molar ratio be 2:1.
In the above method, the balloon pressure described in the specific steps filled with oxygen gas is 1 atmospheric pressure.
Compared with prior art, present invention has an advantage that this method synthesizing mean is novel, with DMF (N, N- dimethyl methyl
Amide) and ammonium iodide as one step of cyanylation agent construct 2- phenylimidazole [1,2-a] pyridine -3- nitrile, synthesizing mean is novel, instead
Mild condition is answered, reaction reagent is cheap and easy to get, realizes cyanogen using DMF (n,N-Dimethylformamide) and ammonium iodide as combination cyanogen source
Glycosylation reaction, wherein DMF (n,N-Dimethylformamide) provides the carbon atom in cyano, and ammonium iodide then provides the nitrogen in cyano
Atom, such cyanalation reaction avoid the generation of hypertoxic gas cyaniding hydrogen, and safe and non-toxic, the development for meeting Green Chemistry is wanted
It asks.
Detailed description of the invention
Fig. 1 is the nuclear magnetic resonance spectroscopy of compound 2- phenylimidazole [1,2-a] pyridine -3- nitrile obtained in embodiment 1；
Fig. 2 is the carbon-13 nmr spectra of compound 2- phenylimidazole [1,2-a] pyridine -3- nitrile obtained in embodiment 1；
Specific embodiment
The invention is further described below by specific embodiment.
Embodiment 1
0.2 mM of pyridine of compound 2- phenylimidazole [1,2-a] is added in the test tube of 25mL, Gerhardite
0.4 mM, 0.4 mM of ammonium iodide, 0.4 mM of acetic acid, 2 milliliters of addition n,N-Dimethylformamide (DMF) as anti-
Solvent is answered, the balloon filled with oxygen is put on, is stirred under 130 degrees Celsius.TLC (thin-layered chromatography) detection after reaction will be anti-
It answers liquid to be cooled to room temperature, removes balloon, be slowly vented unreacted oxygen.Reaction solution filtering, filtrate decompression revolving removal solvent,
Again by column chromatographic isolation and purification, compound 2- phenylimidazole [1,2-a] pyridine -3- nitrile, the step yield 85% are obtained.
Embodiment 2
0.2 mM of pyridine of compound 2- phenylimidazole [1,2-a] is added in the test tube of 25mL, 0.4 mmoles of copper acetate
You, 0.4 mM of ammonium iodide, 0.4 mM of acetic acid, 2 milliliters of addition n,N-Dimethylformamide (DMF) are used as reaction dissolvent,
The balloon filled with oxygen is put on, is stirred under 130 degrees Celsius.TLC (thin-layered chromatography) detection will react liquid cooling after reaction
But room temperature is arrived, balloon is removed, is slowly vented unreacted oxygen.Reaction solution filtering, filtrate decompression revolving removal solvent, then pass through
Column chromatographic isolation and purification obtains compound 2- phenylimidazole [1,2-a] pyridine -3- nitrile, the step yield 15%.
Embodiment 3
0.2 mM of pyridine of compound 2- phenylimidazole [1,2-a] is added in the test tube of 25mL, 0.4 mmoles of copper bromide
You, 0.4 mM of ammonium iodide, 0.4 mM of acetic acid, 2 milliliters of addition n,N-Dimethylformamide (DMF) are used as reaction dissolvent,
The balloon filled with oxygen is put on, is stirred under 130 degrees Celsius.TLC (thin-layered chromatography) tracing detection does not detect that target produces
Object.
Embodiment 4
0.2 mM of pyridine of compound 2- phenylimidazole [1,2-a] is added in the test tube of 25mL, 0.4 milli of cuprous iodide
Mole, 0.4 mM of ammonium iodide, 0.4 mM of acetic acid, it is molten as reaction that 2 milliliters of n,N-Dimethylformamide (DMF) is added
Agent puts on the balloon filled with oxygen, stirs under 130 degrees Celsius.TLC (thin-layered chromatography) tracing detection, does not detect mesh
Mark product.
Embodiment 5
0.2 mM of pyridine of compound 2- phenylimidazole [1,2-a] is added in the test tube of 25mL, 0.4 mmoles of copper chloride
You, 0.4 mM of ammonium iodide, 0.4 mM of acetic acid, 2 milliliters of addition n,N-Dimethylformamide (DMF) are used as reaction dissolvent,
The balloon filled with oxygen is put on, is stirred under 130 degrees Celsius.TLC (thin-layered chromatography) tracing detection does not detect that target produces
Object.
In above-described embodiment, the type of mantoquita has apparent influence to reaction effect.Only made with Gerhardite
For when promotor target product could be obtained with preferable yield.
Claims (7)
1. it is a kind of constructed using DMF (N,N-dimethylformamide) and ammonium iodide as one step of cyanylation agent 2- phenylimidazole [1,
2-a] pyridine -3- nitrile new method, which is characterized in that synthetic route is as follows:
Specific steps are as follows:
It takes compound 1 to be placed in container, promotor, solvent, additive, ammonium iodide is added, puts on the balloon filled with oxygen gas,
It is stirred to react 1-48 hours, is cooled to room temperature after reaction, remove balloon, reaction solution filters, and after evaporating solvent under reduced pressure, obtains slightly
Product obtains compound 2- phenylimidazole [1,2-a] pyridine -3- nitrile through column Chromatographic purification.
2. according to claim 1 a kind of using DMF (N,N-dimethylformamide) and ammonium iodide as cyanylation agent one
The new method of step building 2- phenylimidazole [1,2-a] pyridine -3- nitrile, which is characterized in that the compound 1 is 2- phenylimidazole
[1,2-a] pyridine, the promotor are Gerhardite, and the additive is acetic acid, and the solvent is DMF (N, N- diformazan
Base formamide).
3. according to claim 1 a kind of using DMF (N,N-dimethylformamide) and ammonium iodide as cyanylation agent one
The new method of step building 2- phenylimidazole [1,2-a] pyridine -3- nitrile, which is characterized in that the reaction vessel of the specific steps is
Teat glass.
4. according to claim 1 a kind of using DMF (N,N-dimethylformamide) and ammonium iodide as cyanylation agent one
The new method of step building 2- phenylimidazole [1,2-a] pyridine -3- nitrile, which is characterized in that mantoquita is added in the specific steps
Amount and the molar ratio of compound 1 (2- phenylimidazole [1,2-a] pyridine) are 2:1.
5. according to claim 1 a kind of using DMF (N,N-dimethylformamide) and ammonium iodide as cyanylation agent one
The new method of step building 2- phenylimidazole [1,2-a] pyridine -3- nitrile, which is characterized in that additive is added in the specific steps
Amount and compound 1 (2- phenylimidazole [1,2-a] pyridine) molar ratio be 2:1.
6. according to claim 1 a kind of using DMF (N,N-dimethylformamide) and ammonium iodide as cyanylation agent one
The new method of step building 2- phenylimidazole [1,2-a] pyridine -3- nitrile, which is characterized in that ammonium iodide is added in the specific steps
Amount and compound 1 (2- phenylimidazole [1,2-a] pyridine) molar ratio be 2:1.
7. according to claim 1 a kind of using DMF (N,N-dimethylformamide) and ammonium iodide as cyanylation agent one
The new method of step building 2- phenylimidazole [1,2-a] pyridine -3- nitrile, which is characterized in that filled with oxygen described in the specific steps
The balloon pressure of gas gas is 1 atmospheric pressure.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910713629.3A CN110372697A (en) | 2019-08-02 | 2019-08-02 | Using DMF and ammonium iodide as the new method of cyanylation agent building 2- phenylimidazole [1,2-a] pyridine -3- nitrile |
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| CN201910713629.3A CN110372697A (en) | 2019-08-02 | 2019-08-02 | Using DMF and ammonium iodide as the new method of cyanylation agent building 2- phenylimidazole [1,2-a] pyridine -3- nitrile |
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| CN110372697A true CN110372697A (en) | 2019-10-25 |
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| CN201910713629.3A Withdrawn CN110372697A (en) | 2019-08-02 | 2019-08-02 | Using DMF and ammonium iodide as the new method of cyanylation agent building 2- phenylimidazole [1,2-a] pyridine -3- nitrile |
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| CN (1) | CN110372697A (en) |
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2019
- 2019-08-02 CN CN201910713629.3A patent/CN110372697A/en not_active Withdrawn
Non-Patent Citations (2)
| Title |
|---|
| BINGBO NIU等: "Heterogeneous copper-catalyzed three-component reaction of 2-aminopyridines, acetophenones and benzyl cyanide towards 3-cyanoimidazo[1,2-a]pyridines", 《CATALYSIS COMMUNICATIONS》 * |
| JINHO KIM等: "Copper-Mediated Selective Cyanation of Indoles and 2- Phenylpyridines with Ammonium Iodide and DMF", 《J. AM. CHEM.SOC.》 * |
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