CN106699691A - Synthesis method of alkynyl amidine compound - Google Patents
Synthesis method of alkynyl amidine compound Download PDFInfo
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- CN106699691A CN106699691A CN201611189406.4A CN201611189406A CN106699691A CN 106699691 A CN106699691 A CN 106699691A CN 201611189406 A CN201611189406 A CN 201611189406A CN 106699691 A CN106699691 A CN 106699691A
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- tert
- medicine
- cheap
- butyl isonitrile
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/195—Radicals derived from nitrogen analogues of carboxylic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C239/00—Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
- C07C239/08—Hydroxylamino compounds or their ethers or esters
- C07C239/22—Hydroxylamino compounds or their ethers or esters having oxygen atoms of hydroxylamino groups esterified
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/14—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to acyclic carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The invention is an alkynyl amidine compound obtained by converting cheap t-butyl isonitrile easy to obtain under the simple conditions and widely applied in the fields of medicine, pesticides, petrochemical engineering and the like. The alkynyl amidine compound is characterized by being prepared through the following steps that 1, benzoyl peroxide, secondary amine and anhydrous sodium hydrogen phosphate are used as raw materials to synthesize a benzoyl hydroxylamine compound; 2, the t-butyl isonitrile, cuprous chloride, cesium carbonate, triphenylphosphine, the benzoyl hydroxylamine compound and a phenylacetylene compound are added to a 25 ml reaction tube, toluene is used as a solvent to perform reaction through heating to reach 60-110 DEG C under the anaerobic condition; after the reaction is completed, the reaction fluid is filtered, washed, dried and filtered, and then column chromatography separation is performed to obtain an amidine product. The amidine compound obtained through the method is widely applied in the fields of medicine, pesticides, petrochemical engineering and the like.
Description
Technical field
The present invention is a kind of synthetic method of alkynyl amidine compound.By tert-butyl isonitrile cheap and easy to get better simply
Under the conditions of be converted into all wide variety of amidine compound in field such as medicine, agricultural chemicals and petrochemical industry.
Technical background
Amidine be nitrogen substitution carboxylic acid analog, some amidine compounds be some have physiologically active material fragment,
Meanwhile, their still important synthetic intermediates in organic synthesis.Amidine is very important compound, is widely used in antibiosis
Element, diuretics, antiphlogistic, pest repellant and broad spectrum acaricides, in all extensive uses of the field such as agricultural chemicals and petrochemical industry.For azepine
The preparation of cycle compound, amidine is also useful synthetic fibers.Amidine is also known as in Imidamide, i.e. amide molecule.
With the expansion of the purposes of amidine, the research of its synthetic method also result in scientist and more pay attention to.1975
The synthesis and application to amidine such as Gautier has carried out more detailed summary, and Boy also reviews the synthesis progress of amidine within 1991,
Liu Yi peaks in 1996 etc. also review synthesis and the application study progress of amidine.The classical synthetic method of amidine is amide acetals method, nitrile
Ammonolysis process and orthoformic acid ester process.Recent domestic has also carried out larger improvement to these methods, and raw material is easy to get, makes synthesis
Technique simplifies and improves yield.The present invention is that amidine class is converted under the conditions of better simply with tert-butyl isonitrile cheap and easy to get
Compound, is that the synthesis of amidine compound increases new method.
The content of the invention
The present invention be with tert-butyl isonitrile cheap and easy to get be amidino groups originate, cheap copper catalyst next step generate cure
The all wide variety of amidine compound in the fields such as medicine, agricultural chemicals and petrochemical industry.
Specific method be tert-butyl isonitrile be amidino groups source, with stannous chloride as catalyst, cesium carbonate as alkali, in triphenyl
Under phosphine catalyst, act on the fields such as step generation medicine, agricultural chemicals and petrochemical industry with acetylenic, benzoyl hydroxylamine class material and all extensively should
Amidine compound.Product obtains pure amidine class and produces by filtering, alkali cleaning, washing, drying process, eventually through column chromatography method
Thing.
The technical solution adopted by the present invention is as follows：
A kind of synthetic method of alkynyl amidine compound, comprises the following steps：
1) it is Material synthesis benzoyl hydroxylamine class compound with benzoyl peroxide, secondary amine, ADSP.
2) tert-butyl isonitrile, stannous chloride, cesium carbonate, triphenylphosphine, benzoyl hydroxylamine class, phenylacetylene compound are added
25ml reaction tubes with toluene as solvent under anaerobic, be warming up to 60-110 DEG C of reaction.After the completion of reaction, reaction solution mistake successively
Filter, washing, dry, filtering, the amidine class product of column chromatography for separation purification.
In the above method, and the compound for obtaining is characterized by nuclear magnetic resonance spectrometer and melting point apparatus, with document pair
It is alkynyl amidine compound than final product.
In the above method, tert-butyl isonitrile, stannous chloride, cesium carbonate, triphenylphosphine, benzoyl hydroxylamine class, phenylacetylene
The reaction time of compound is 6-12 hours.
The present invention is a kind of synthetic method of alkynyl amidine compound.By tert-butyl isonitrile cheap and easy to get better simply
Under the conditions of be converted into all wide variety of amidine compound in field such as medicine, agricultural chemicals and petrochemical industry.
Brief description of the drawings
The synthesis of Fig. 1 benzoyl hydroxylamine class compounds
The synthesis of Fig. 2 amidine compounds
Specific embodiment
It is below specific embodiment of the invention.
The synthetic route chart of the embodiment of the present invention, as illustrated, synthesis is carried out in two steps：
The first step, the synthesis of benzoyl hydroxylamine class compound：Accurately weigh 4.84g benzoyl peroxides and 4.26g is anhydrous
Disodium hydrogen phosphate joins it into dry 100mL round-bottomed flasks, adds 20-40ml DMF room temperatures and stirs
Mix 10-30 minutes, continue to react 1-24 hours into reaction solution after secondary amine is added dropwise after solid dissolving.After reaction terminates, 20- is used
60ml water quenching reaction, reaction solution carries out column chromatography, obtains intermediate product after extracting, washing, dry.Its reaction expression formula
It is Fig. 1.
Second step, the synthesis of amidine compound：By tert-butyl isonitrile, stannous chloride, cesium carbonate, triphenylphosphine, acetylenic, benzene
Formyl hydroxylamine compound adds 25ml reaction tubes, and 60-110 DEG C, reaction are risen under anaerobic by solvent reaction of toluene
After end, reaction solution is filtered, washs, dries, filtered successively, and column chromatography for separation purifies to obtain final product, weighs and calculate yield,
Characterized with nuclear-magnetism, its reaction expression formula is Fig. 2.
Example one, the synthesis of (the E)-N- tert-butyl group -1- phenylacetylene -1- morpholine -1- imines
Weigh tert-butyl isonitrile 0.063g, phenylacetylene 0.051g, 4- benzoyl morpholine 0.154g, stannous chloride
0.005g, cesium carbonate 0.325g, triphenylphosphine 0.014g, 3.0ml toluene add the 25mL reaction tubes equipped with magnetic stir bar, put
The stirring reaction 12h at reaction under oxygen free condition is heated to 110 DEG C.After reaction terminates, reaction solution filters, washs, drying successively,
Filtering, column chromatography for separation purification obtains brown solid 0.078g (yield is 58%).
Example two, the synthesis of (the E)-N- tert-butyl group -1- phenylacetylene bases -1-N, N diisopropyl -1- imines
Weigh tert-butyl isonitrile 0.063g, phenylacetylene 0.051g, benzoyl-N, N diisopropyl azanol 0.15g, chlorination
Cuprous 0.005g, cesium carbonate 0.325g, triphenylphosphine 0.014g, 3.0ml toluene add the 25mL equipped with magnetic stir bar to react
Pipe, is placed in stirring reaction 12h at reaction is heated to 110 DEG C under oxygen free condition.After reaction terminates, reaction solution filters, washs successively,
Dry, filter, column chromatography for separation purification obtains yellow solid 0.072g (yield is 52%).
Example three, the synthesis of (E)-N- tert-butyl groups -1- (4- chlorobenzenes acetenyl) -1- morpholine -1- imines
Weigh tert-butyl isonitrile 0.063g, 4- chlorobenzene acetylene 0.069g, 4- benzoyl morpholine 0.154g, stannous chloride
0.005g, cesium carbonate 0.325g, triphenylphosphine 0.014g, 3.0ml toluene add the 25mL reaction tubes equipped with magnetic stir bar, put
The stirring reaction 12h at reaction under oxygen free condition is heated to 110 DEG C.After reaction terminates, reaction solution filters, washs, drying successively,
Filtering, column chromatography for separation purification obtains brown solid 0.098g (yield is 65%).
Claims (9)
1. it is a kind of that tert-butyl isonitrile cheap and easy to get is converted into medicine, agricultural chemicals and petrochemical industry etc. under the conditions of better simply
The synthetic method of all wide variety of amidine compound in field, it is comprised the following steps：
1) it is Material synthesis benzoyl hydroxylamine class compound with benzoyl peroxide, secondary amine, ADSP；
2) by tert-butyl isonitrile (0.75mmol), stannous chloride (0.05mmol), cesium carbonate (1.0mmol), triphenylphosphine
(0.05mmol), benzoyl hydroxylamine class (0.5mmol), phenylacetylene (0.5mmol) compound addition 25ml reaction tubes are with toluene
Solvent under anaerobic, is warmed up to 60-110 DEG C and reacts 6-12 hours.After the completion of reaction, reaction solution is filtered, washs, done successively
Dry, filtering, column chromatography for separation purifies to obtain amidine class product.
2. it is as claimed in claim 1 a kind of by tert-butyl isonitrile cheap and easy to get be converted under the conditions of better simply medicine,
The synthetic method of all wide variety of amidine compound in the field such as agricultural chemicals and petrochemical industry, its synthetic route is：
①
②
3. it is a kind of as claimed in claim 1 that tert-butyl isonitrile cheap and easy to get is converted into doctor under the conditions of better simply
The synthetic method of all wide variety of amidine compound in the fields such as medicine, agricultural chemicals and petrochemical industry, it is characterized in that：Described in second step
Solvent be toluene.
4. it is a kind of as claimed in claim 1 that tert-butyl isonitrile cheap and easy to get is converted into doctor under the conditions of better simply
The synthetic method of all wide variety of amidine compound in the fields such as medicine, agricultural chemicals and petrochemical industry, it is characterized in that：The reaction temperature of second step
Spend is 60-110 DEG C.
5. it is a kind of as claimed in claim 1 that tert-butyl isonitrile cheap and easy to get is converted into doctor under the conditions of better simply
The synthetic method of all wide variety of amidine compound in the fields such as medicine, agricultural chemicals and petrochemical industry, it is characterized in that：The reaction of second step
Time is 6-12 hours.
6. it is a kind of as claimed in claim 1 that tert-butyl isonitrile cheap and easy to get is converted into doctor under the conditions of better simply
The synthetic method of all wide variety of amidine compound in the fields such as medicine, agricultural chemicals and petrochemical industry, it is characterized in that：It is used in second step
Alkali be cesium carbonate.
7. it is a kind of as claimed in claim 1 that tert-butyl isonitrile cheap and easy to get is converted into doctor under the conditions of better simply
The synthetic method of all wide variety of amidine compound in the fields such as medicine, agricultural chemicals and petrochemical industry, it is characterized in that：It is used in second step
Catalyst be stannous chloride.
8. it is a kind of as claimed in claim 1 that tert-butyl isonitrile cheap and easy to get is converted into doctor under the conditions of better simply
The synthetic method of all wide variety of amidine compound in the fields such as medicine, agricultural chemicals and petrochemical industry, it is characterized in that：It is used in second step
Part be triphenylphosphine.
9. it is a kind of as claimed in claim 1 that tert-butyl isonitrile cheap and easy to get is converted into doctor under the conditions of better simply
The synthetic method of all wide variety of amidine compound in the fields such as medicine, agricultural chemicals and petrochemical industry, it is characterized in that：It is used in second step
Tert-butyl isonitrile, stannous chloride, cesium carbonate, triphenylphosphine, benzoyl hydroxylamine class, acetylenic raw material rate of charge are 1.5:0.1:2.0:
0.1:1.0:1.0。
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107573262A (en) * | 2017-09-21 | 2018-01-12 | 沅江华龙催化科技有限公司 | A kind of synthetic method of amidine compound |
| CN110317221A (en) * | 2019-06-24 | 2019-10-11 | 华南理工大学 | A kind of polysubstituted alkynes amidine compound and its preparation method and application |
| CN114213272A (en) * | 2021-12-24 | 2022-03-22 | 江南大学 | Synthetic method of arylethynyl formamide compound |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104030961B (en) * | 2014-06-04 | 2016-04-13 | 常州大学 | The preparation method of a kind of polysubstituted ring amidine |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104030961B (en) * | 2014-06-04 | 2016-04-13 | 常州大学 | The preparation method of a kind of polysubstituted ring amidine |
Non-Patent Citations (3)
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| K. KISHORE R. TETALA ET AL.: "Palladium-catalysed three component synthesis of α,β-unsaturated", 《TETRAHEDRON LETTERS》 * |
| MERLE ARROWSMITH ET AL.: "Alkaline earth catalysis for the 100% atom-efficient three component assembly of imidazolidin-2-ones", 《CHEM. COMMUN.》 * |
| TING TANG ET AL.: "Palladium-Catalyzed Carbonylative Sonogashira Coupling of Aryl Bromides via tert-Butyl Isocyanide Insertion", 《J. ORG. CHEM.》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107573262A (en) * | 2017-09-21 | 2018-01-12 | 沅江华龙催化科技有限公司 | A kind of synthetic method of amidine compound |
| CN107573262B (en) * | 2017-09-21 | 2019-11-05 | 沅江华龙催化科技有限公司 | A kind of synthetic method of amidine compound |
| CN110317221A (en) * | 2019-06-24 | 2019-10-11 | 华南理工大学 | A kind of polysubstituted alkynes amidine compound and its preparation method and application |
| CN114213272A (en) * | 2021-12-24 | 2022-03-22 | 江南大学 | Synthetic method of arylethynyl formamide compound |
| CN114213272B (en) * | 2021-12-24 | 2022-12-27 | 江南大学 | Synthetic method of arylethynyl formamide compound |
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Effective date of registration: 20210125 Address after: 226000 lot 068, phase I, Lingang Industrial Zone, yangkougang Economic Development Zone, Rudong County, Nantong City, Jiangsu Province Patentee after: WANBO NEW MATERIAL TECHNOLOGY (NANTONG) Co.,Ltd. Address before: No. 1800 road 214122 Jiangsu Lihu Binhu District City of Wuxi Province Patentee before: Jiangnan University |
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