CN110437225A - 2-(2- naphthalene is constructed using DMF and ammonium iodide as cyanylation agent) imidazoles [1,2-a] pyridine -3- nitrile - Google Patents
2-(2- naphthalene is constructed using DMF and ammonium iodide as cyanylation agent) imidazoles [1,2-a] pyridine -3- nitrile Download PDFInfo
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- CN110437225A CN110437225A CN201910712835.2A CN201910712835A CN110437225A CN 110437225 A CN110437225 A CN 110437225A CN 201910712835 A CN201910712835 A CN 201910712835A CN 110437225 A CN110437225 A CN 110437225A
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- 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
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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- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile.This method is with 2- (2- naphthalene) imidazoles [1,2-a] pyridine is as reaction raw materials, 2- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile is constructed using DMF (n,N-Dimethylformamide) and ammonium iodide as one step of cyanylation agent.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- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile new side
Method.
Background technique
2- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile compounds are a kind of very important pharmaceutical intermediates, can be used
In synthesizing the various drug molecules with pharmaceutical activity, the structural framework for being included using such compound can be with structure as starting material
Build our known drug molecule grains of sand pyrrole denier and the anesthesiophore Necopidem of tool with antidepressant effect.Traditional cyanogen
Base reagent, such as Cymag, potassium cyanide, copper cyanider and zinc cyanide often generate severe toxicity in cyanalation process
Hydrogen cyanide other, cause serious environmental pollution, while keeping last handling process extremely inconvenient, there are very big security risks.At this
Under the research background of sample, we have proposed one kind using DMF (n,N-Dimethylformamide) and ammonium iodide as cyanylation agent
One step constructs the new method of 2- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile, and this method is with DMF (n,N-Dimethylformamide)
Cyanalation reaction is realized as combination cyanogen source with ammonium iodide, and wherein it is former to provide the carbon in cyano by DMF (n,N-Dimethylformamide)
Son, and ammonium iodide then provides the nitrogen-atoms in cyano, such cyanalation reaction avoids the generation of hypertoxic gas cyaniding hydrogen, safety
It is nontoxic, meet the demand for development of Green Chemistry.Its synthetic route is as follows:
2- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile that the present invention synthesizes, structural formula are as follows:
The invention constructs 2- (2- naphthalene) using DMF (N,N-dimethylformamide) and ammonium iodide as one step of cyanylation agent
Imidazoles [1,2-a] pyridine -3- nitrile provides a novel synthetic route for the synthesis of such compound.The invention synthesizes hand
Duan Xinying, 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 with
The carbon atom in cyano is provided as cyanylation agent, and ammonium iodide then provides the nitrogen-atoms in cyano, such combination cyanogen source peace
Atoxic 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 (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile.This method is using 2- (2- naphthalene) imidazoles [1,2-a] pyridine as instead
Answer raw material, using DMF (n,N-Dimethylformamide) and ammonium iodide as one step of cyanylation agent building 2- (2- naphthalene) imidazoles [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, N, N- dimethyl
Formamide 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
Nitrogen-atoms in cyano, 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- (2- naphthalene) miaow using DMF (N,N-dimethylformamide) and ammonium iodide as one step of cyanylation agent
The new method of azoles [1,2-a] pyridine -3- nitrile, synthetic route are as follows:
In the above method, 2- (2- naphthalene) imidazoles [1, the 2-a] pyridine -3- nitrile is by compound 1 through cyanalation reaction one
Step is made；The compound 1 is 2- (2- naphthalene) imidazoles [1,2-a] pyridine, the specific steps are as follows:
It takes compound 1 (2- (2- naphthalene) imidazoles [1,2-a] pyridine) to be placed in container, promotor and solvent is added, puts on
Balloon filled with oxygen gas is stirred to react 1-48 hours, is cooled to room temperature after reaction, removes balloon, and reaction solution filters,
After evaporating solvent under reduced pressure, crude product is obtained, obtains compound 2- (2- naphthalene) imidazoles [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 (2- (2- naphthalene) imidazoles [1,2-a] of compound 1 of mantoquita are added in the above method, in the specific steps
Pyridine) molar ratio be 2:1.
The amount and (2- (2- naphthalene) imidazoles [1,2- of compound 1 of additive are added in the above method, in the specific steps
A] pyridine) molar ratio be 2:1.
The amount and (2- (2- naphthalene) imidazoles [1,2- of compound 1 of ammonium iodide are added in the above method, in the specific steps
A] 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- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile, synthesizing mean is new
Grain husk, reaction condition is mild, and reaction reagent is cheap and easy to get, using DMF (n,N-Dimethylformamide) and ammonium iodide as combination cyanogen source
Realize cyanalation reaction, wherein DMF (n,N-Dimethylformamide) provides the carbon atom in cyano, and ammonium iodide then provides cyano
In nitrogen-atoms, such cyanalation reacts avoids the generation of hypertoxic gas cyaniding hydrogen, safe and non-toxic, meets the hair of Green Chemistry
Exhibition requires.
Detailed description of the invention
Fig. 1 is the hydrogen nuclear magnetic resonance of compound 2- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile obtained in embodiment 1
Spectrum；
Fig. 2 is the nuclear magnetic resonance carbon of compound 2- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile obtained in embodiment 1
Spectrum；
Specific embodiment
The invention is further described below by specific embodiment.
Embodiment 1
0.2 mM of pyridine of compound 2- (2- naphthalene) imidazoles [1,2-a] is added in the test tube of 25mL, three nitric hydrates
0.4 mM of copper, 0.4 mM of ammonium iodide, 0.4 mM of acetic acid, n,N-Dimethylformamide (DMF) 2 milliliters of conducts are added
Reaction dissolvent puts on the balloon filled with oxygen, stirs under 130 degrees Celsius.TLC (thin-layered chromatography) detection after reaction will
Reaction solution is cooled to room temperature, removes balloon, is slowly vented unreacted oxygen.Reaction solution filtering, filtrate decompression revolving removal are molten
Agent, then by column chromatographic isolation and purification, obtain compound 2- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile, the step yield
78%.
Embodiment 2
0.2 mM of pyridine of compound 2- (2- naphthalene) imidazoles [1,2-a] is added in the test tube of 25mL, copper acetate 0.4
MM, 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) is detected after reaction by reaction solution
It is cooled to room temperature, removes balloon, is slowly vented unreacted oxygen.Reaction solution filtering, filtrate decompression revolving removal solvent, then lead to
Column chromatographic isolation and purification is crossed, compound 2- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile, the step yield 12% are obtained.
Embodiment 3
0.2 mM of pyridine of compound 2- (2- naphthalene) imidazoles [1,2-a] is added in the test tube of 25mL, copper bromide 0.4
MM, 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 4
0.2 mM of pyridine of compound 2- (2- naphthalene) imidazoles [1,2-a] is added in the test tube of 25mL, cuprous iodide
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) tracing detection, is not detected
To target product.
Embodiment 5
0.2 mM of pyridine of compound 2- (2- naphthalene) imidazoles [1,2-a] is added in the test tube of 25mL, copper chloride 0.4
MM, 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.
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. a kind of construct 2- (2- naphthalene) imidazoles using DMF (N,N-dimethylformamide) and ammonium iodide as one step of cyanylation agent
The new method of [1,2-a] pyridine -3- nitrile, 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- (2- naphthalene) imidazoles [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- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile, which is characterized in that the compound 1 is 2- (2- naphthalene
Base) imidazoles [1,2-a] pyridine, the promotor be Gerhardite, the additive be acetic acid, the solvent be DMF (N,
Dinethylformamide).
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- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile, which is characterized in that the container 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- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile, which is characterized in that copper is added in the specific steps
The amount of salt and the molar ratio of compound 1 (2- (2- naphthalene) imidazoles [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- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile, which is characterized in that be added and add in the specific steps
The molar ratio of the amount and compound 1 (2- (2- naphthalene) imidazoles [1,2-a] pyridine) that add agent is 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- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile, which is characterized in that iodine is added in the specific steps
The molar ratio of the amount and compound 1 (2- (2- naphthalene) imidazoles [1,2-a] pyridine) of changing ammonium is 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- (2- naphthalene) imidazoles [1,2-a] pyridine -3- nitrile, which is characterized in that filled described in the specific steps
The balloon pressure for having oxygen gas is 1 atmospheric pressure.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910712835.2A CN110437225A (en) | 2019-08-02 | 2019-08-02 | 2-(2- naphthalene is constructed using DMF and ammonium iodide as cyanylation agent) imidazoles [1,2-a] pyridine -3- nitrile |
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| CN201910712835.2A CN110437225A (en) | 2019-08-02 | 2019-08-02 | 2-(2- naphthalene is constructed using DMF and ammonium iodide as cyanylation agent) imidazoles [1,2-a] pyridine -3- nitrile |
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| CN110437225A true CN110437225A (en) | 2019-11-12 |
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| CN201910712835.2A Withdrawn CN110437225A (en) | 2019-08-02 | 2019-08-02 | 2-(2- naphthalene is constructed using DMF and ammonium iodide as cyanylation agent) imidazoles [1,2-a] pyridine -3- nitrile |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104926811A (en) * | 2015-06-17 | 2015-09-23 | 浙江大学 | Synthetic method for 3-cyano group imidazo [1, 2-a] pyridine compounds and application thereof |
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2019
- 2019-08-02 CN CN201910712835.2A patent/CN110437225A/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104926811A (en) * | 2015-06-17 | 2015-09-23 | 浙江大学 | Synthetic method for 3-cyano group imidazo [1, 2-a] pyridine compounds and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| JINHO KIM 等: "Copper-Mediated Selective Cyanation of Indoles and 2-Phenylpyridines with Ammonium Iodide and DMF", 《ORGANIC LETTERS》 * |
| JINHO KIM等: "Copper-Mediated Selective Cyanation of Indoles and 2- Phenylpyridines with Ammonium Iodide and DMF", 《J. AM. CHEM.SOC.》 * |
| QIAODONG WEN 等: "Copper-mediated three-component synthesis of 3-cyanoimidazo[1,2-a]pyridines", 《CHEM. COMMUN.》 * |
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