CN107739379A - A kind of imidazoles [1,2 a:3,4 a '] and two pyridine salt compounds synthetic method - Google Patents

A kind of imidazoles [1,2 a:3,4 a '] and two pyridine salt compounds synthetic method Download PDF

Info

Publication number
CN107739379A
CN107739379A CN201710797018.2A CN201710797018A CN107739379A CN 107739379 A CN107739379 A CN 107739379A CN 201710797018 A CN201710797018 A CN 201710797018A CN 107739379 A CN107739379 A CN 107739379A
Authority
CN
China
Prior art keywords
imidazoles
pyridine
halogen
salt compounds
synthetic method
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201710797018.2A
Other languages
Chinese (zh)
Inventor
李亭
杨昱涵
李波
杨萍
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nanyang Normal University
Original Assignee
Nanyang Normal University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nanyang Normal University filed Critical Nanyang Normal University
Priority to CN201710797018.2A priority Critical patent/CN107739379A/en
Publication of CN107739379A publication Critical patent/CN107739379A/en
Pending legal-status Critical Current

Links

Classifications

    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/14—Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses a kind of imidazoles [1,2a:3,4‑a'] and two pyridine salt compounds synthetic method.The present invention is by the way that toward pyridine radicals pyridine compounds, alpha-bromoacetophenone compound are sequentially added in reaction tube, cobalt/copper is total to catalyst system and catalyzing, cesium salt and solvent；Reaction tube is placed under conditions of 120 140 DEG C in air atmosphere and is stirred reaction, its stirring reaction time >=24h；After completion of the reaction, reaction tube is cooled to room temperature, and reactant mixture is filtered, concentration, then post is crossed by column chromatography, uses the mixed solution of ethyl acetate and dichloromethane to be eluted for eluant, eluent, obtained fraction carries out obtaining the compound after solvent is removed in vacuum distillation.The raw material and catalyst system and catalyzing of the present invention is cheap and easy to get, and operating procedure is easy, and reaction condition is gentle, and yield is higher, is advantageous to expansion scale and prepares or carry out industrial applications, is a synthetic route efficiently, economic.

Description

A kind of imidazoles [1,2-a:3,4-a '] and two pyridine salt compounds synthetic method
Technical field
The invention belongs to field of natural medicinal chemistry, and in particular to a kind of imidazoles [1,2-a:3,4-a'] and two pyridine salts The synthetic method of compound.
Background technology
Nitrogen-containing hetero cyclics occupy highly important status in chemical system, and there is largely contain in nature Heterocyclic nitrogen compound is such as:Nucleic acid, vitamin, hormone, antibiotic and alkaloid.It is special that nitrogenous fused heterocycle compounds have Bioactivity and physicochemical property, have in terms of medicine, agricultural chemicals, organic dyestuff and functional material and generally apply.Imidazoles [1,2- a:3,4-a'] and two pyridine salt compounds are a kind of important nitrogenous fused heterocycle compounds, in last century the eighties, are led to Picoline is crossed, pyridine, sulfur dioxide, chlorobenzoyl chloride and potassium hydroxide multi-component reaction realize imidazoles [1,2-a:3,4-a'] And two pyridiniujm skeleton the first synthesis.Imidazoles [1,2-a:3,4-a'] and two pyridine salt compounds have special structure, Property, important bioactivity and medical value；Therefore develop simple efficient method and realize imidazoles [1,2-a:3,4-a'] simultaneously The synthesis of two pyridine salt compounds has great researching value.
The content of the invention
The invention aims to solve the deficiencies in the prior art to propose a kind of imidazoles [1,2-a:3,4-a'] and two The synthetic method of pyridine salt compounds, using pyridine radicals pyridine compounds as substrate, cobalt/copper altogether under catalyst system and catalyzing with bromine Coupling reaction and intramolecular cyclization process for acetophenone compounds realize imidazoles [1,2-a3,4-a'] and two pyridiniujms Class compound efficiently synthesizes；Its substrate universality is preferable, and yield is higher, and easily operated.
To achieve these goals, the present invention uses following technical scheme：A kind of imidazoles [1,2-a:3,4-a'] and two pyrroles The synthetic method of pyridine salt compounds, comprises the following steps：
(1) toward pyridine radicals pyridine compounds, alpha-bromoacetophenone compound are sequentially added in reaction tube, cobalt/copper is catalyzed altogether System, cesium salt and solvent；
(2) reaction is stirred under conditions of reaction tube being placed in into 120-140 DEG C in air atmosphere, its stirring reaction time >= 24h；
(3) after completion of the reaction, reaction tube is cooled to room temperature, and reactant mixture is filtered, and concentration, then crosses post by column chromatography, The mixed solution of ethyl acetate and dichloromethane is used to be eluted for eluant, eluent, obtained fraction carries out vacuum distillation and removes solvent After obtain imidazoles [1,2-a:3,4-a'] and two pyridine salt compounds；Its chemical equation is：
Wherein, R1For hydrogen, unsubstituted or the alkyl, halogen and the alkoxy that is unsubstituted or being optionally substituted by halogen that are optionally substituted by halogen In one kind；R2For hydrogen, unsubstituted or the alkyl, halogen and the alkoxy that is unsubstituted or being optionally substituted by halogen that are optionally substituted by halogen In one kind；R3For hydrogen, unsubstituted or the alkyl, halogen and the alkoxy that is unsubstituted or being optionally substituted by halogen that are optionally substituted by halogen In one kind.
Further, catalyst system and catalyzing includes CoCl to described cobalt/copper altogether2And mantoquita, wherein mantoquita is CuI or CuBr；Institute It is Cs to state cesium salt2CO3Or CsI；The solvent is one kind in toluene, dichloroethanes and chlorobenzene.
Further, 0.3-1.2mmol bromines are added per 0.1-0.4mmol pyridine radicals pyridine compounds in step (1) For acetophenone compounds, the common catalyst system and catalyzing of 7.5-30mol% cobalts/copper；0.3-1.2mmol cesium salts and 1-6mL solvents；Wherein Catalyst system and catalyzing includes 2.5-10mol%CoCl to cobalt/copper altogether2With 5-20mol% CuI or CuBr.
Further, the ratio of the amount of the material of pyridine radicals pyridine compounds and cesium salt is in step (1)：1:3.
Further, catalyst system and catalyzing includes CoCl to the cobalt/copper altogether2And mantoquita, CoCl2Molar percentage with mantoquita is 1:1-2.5, wherein mantoquita are CuI or CuBr.
Further, 0.60mmol bromoacetophenones are sequentially added per 0.20mmol pyridine radicals pyridones in step (1), The common catalyst system and catalyzing of 15mol% cobalts/copper, 0.6mmol Cs2CO3With 2mL toluene；Wherein, catalyst system and catalyzing includes 5mol% to cobalt/copper altogether CoCl2And 10mol%CuI.
Further, reaction tube is stirred reaction under conditions of being placed in 130 DEG C in step (2).
Further, the concentration process in step (3) is carried out under conditions of temperature >=50 DEG C；Described fraction exists Vacuum distillation is carried out under conditions of temperature >=50 DEG C and removes solvent.
Further, the silicagel column for 200-300 mesh that column chromatography uses described in step (3)；The ethyl acetate and Example ethyl acetate by volume in the mixed solution of dichloromethane：Dichloromethane=1:1.
Further, the R1Substituting group position is two or three-digit；R2Substituting group position is 9 or 10；R3Substituent position It is set to 11 or 12.
The device have the advantages that it is：Raw material and catalyst system and catalyzing are cheap and easy to get used by the inventive method, technique Flow is short, operating procedure is easy, without the gentle reaction condition of anhydrous and oxygen-free operation, while is easy to open up product structure Exhibition, be advantageous to expansion scale and prepare or carry out industrial applications, be a synthetic route efficiently, economic；Pyridine radicals pyridone Coupling reaction and intramolecular cyclization, production occur under cobalt/copper altogether catalyst system and catalyzing with alpha-bromoacetophenone compound for class compound Thing functional group tolerance is strong, and yield is higher, and operating procedure is few, is environment-friendly green syt side without separating intermediate product Method；The inventive method has good regioselectivity, can easily prepare imidazoles [1,2-a:3,4-a'] and two pyridiniujms Class compound, it is easy to imidazoles [1,2-a:3,4-a'] and two pyridine salt compounds carry out design and rational, synthesis and further Widen follow-up study.
Brief description of the drawings
Fig. 1 is imidazoles [1,2-a in the embodiment of the present invention 2:3,4-a'] and two pyridine salt compounds (3aa)1H NMR Collection of illustrative plates；
Fig. 2 is imidazoles [1,2-a in the embodiment of the present invention 2:3,4-a'] and two pyridine salt compounds (3aa)13C NMR scheme Spectrum；
Fig. 3 is imidazoles [1,2-a in the embodiment of the present invention 3:3,4-a'] and two pyridine salt compounds (3ba)1H NMR scheme Spectrum；
Fig. 4 is imidazoles [1,2-a in the embodiment of the present invention 3:3,4-a'] and two pyridine salt compounds (3ba)13C NMR scheme Spectrum；
Fig. 5 is imidazoles [1,2-a in the embodiment of the present invention 4:3,4-a'] and two pyridine salt compounds (3ca)1H NMR scheme Spectrum；
Fig. 6 is imidazoles [1,2-a in the embodiment of the present invention 4:3,4-a'] and two pyridine salt compounds (3ca)13C NMR scheme Spectrum；
Fig. 7 is imidazoles [1,2-a in the embodiment of the present invention 5:3,4-a'] and two pyridine salt compounds (3ea)1H NMR scheme Spectrum；
Fig. 8 is imidazoles [1,2-a in the embodiment of the present invention 5:3,4-a'] and two pyridine salt compounds (3ea)13C NMR scheme Spectrum；
Fig. 9 is imidazoles [1,2-a in the embodiment of the present invention 6:3,4-a'] and two pyridine salt compounds (3eb)1H NMR scheme Spectrum；
Figure 10 is imidazoles [1,2-a in the embodiment of the present invention 6:3,4-a'] and two pyridine salt compounds (3eb)13C NMR scheme Spectrum；
Embodiment
The above of the present invention is described in further detail by the following examples, but this should not be understood Following embodiment is only limitted to for the scope of the above-mentioned theme of the present invention, it is all to realize that technology belongs to this based on the above of the present invention Invent the scope of protection.
A kind of imidazoles [1,2-a:3,4-a'] and two pyridine salt compounds synthetic method, comprise the following steps：
(1) toward pyridine radicals pyridine compounds, alpha-bromoacetophenone compound are sequentially added in reaction tube, cobalt/copper is catalyzed altogether System, cesium salt and solvent；
(2) reaction is stirred under conditions of reaction tube being placed in into 120-140 DEG C in air atmosphere, its stirring reaction time >= 24h；
(3) after completion of the reaction, reaction tube is cooled to room temperature, and reactant mixture is filtered, and concentration, then crosses post by column chromatography, The mixed solution of ethyl acetate and dichloromethane is used to be eluted for eluant, eluent, obtained fraction carries out vacuum distillation and removes solvent After obtain imidazoles [1,2-a:3,4-a'] and two pyridine salt compounds；Its chemical equation is：
Wherein, R1For hydrogen, unsubstituted or the alkyl, halogen and the alkoxy that is unsubstituted or being optionally substituted by halogen that are optionally substituted by halogen In one kind；R2For hydrogen, unsubstituted or the alkyl, halogen and the alkoxy that is unsubstituted or being optionally substituted by halogen that are optionally substituted by halogen In one kind；R3For hydrogen, unsubstituted or the alkyl, halogen and the alkoxy that is unsubstituted or being optionally substituted by halogen that are optionally substituted by halogen In one kind.
Further, catalyst system and catalyzing includes CoCl to described cobalt/copper altogether2And mantoquita, wherein mantoquita is CuI or CuBr；Institute It is Cs to state cesium salt2CO3Or CsI；The solvent is one kind in toluene, dichloroethanes and chlorobenzene.
Further, 0.3-1.2mmol bromines are added per 0.1-0.4mmol pyridine radicals pyridine compounds in step (1) For acetophenone compounds, the common catalyst system and catalyzing of 7.5-30mol% cobalts/copper；0.3-1.2mmol cesium salts and 1-6mL solvents；Wherein Catalyst system and catalyzing includes 2.5-10mol%CoCl to cobalt/copper altogether2With 5-20mol% CuI or CuBr.
Further, the ratio of the amount of the material of pyridine radicals pyridine compounds and cesium salt is in step (1)：1:3.
Further, catalyst system and catalyzing includes CoCl to the cobalt/copper altogether2And mantoquita, CoCl2Molar percentage with mantoquita is 1:1-2.5, wherein mantoquita are CuI or CuBr.
Further, 0.60mmol bromoacetophenones are sequentially added per 0.20mmol pyridine radicals pyridones in step (1), The common catalyst system and catalyzing of 15mol% cobalts/copper, 0.6mmol Cs2CO3With 2mL toluene；Wherein, catalyst system and catalyzing includes 5mol% to cobalt/copper altogether CoCl2And 10mol%CuI.
Further, reaction tube is stirred reaction under conditions of being placed in 130 DEG C in step (2).
Further, the concentration process in step (3) is carried out under conditions of temperature >=50 DEG C；Described fraction exists Vacuum distillation is carried out under conditions of temperature >=50 DEG C and removes solvent.
Further, the silicagel column for 200-300 mesh that column chromatography uses described in step (3)；The ethyl acetate and Example ethyl acetate by volume in the mixed solution of dichloromethane：Dichloromethane=1:1.
Further, the R1Substituting group position is two or three-digit；R2Substituting group position is 9 or 10；R3Substituent position It is set to 11 or 12.
R described above1For hydrogen, unsubstituted or the alkyl, the halogen and unsubstituted or taken by halogen that are optionally substituted by halogen One kind in the alkoxy in generation, such as R1Can be hydrogen, methyl, chlorine, fluorine, trifluoromethyl or benzyloxy；R2For hydrogen, it is unsubstituted or One kind in the alkyl that is optionally substituted by halogen, halogen and the unsubstituted or alkoxy that is optionally substituted by halogen, such as R2Can be hydrogen, first Base, fluorine or trifluoromethyl；R3For hydrogen, unsubstituted or the alkyl, the halogen and unsubstituted or be optionally substituted by halogen that are optionally substituted by halogen Alkoxy in one kind, such as R3Can be hydrogen, methyl, methoxyl group, chlorine, fluorine or ethyl；Synthetic method optimal conditions of the present invention In when the use of solvent being toluene, cesium salt Cs2CO3Or mantoquita, when being CuI, its product yield is of a relatively high.
Below by specific embodiment and accompanying drawing the present invention will be further explained explanation.
Embodiment 1
A kind of imidazoles [1,2-a:3,4-a'] and two pyridine salt compounds synthetic method, comprise the following steps：
(1) toward sequentially adding 0.1-0.4mmol pyridine radicals pyridine compounds, 0.3-1.2mmol bromobenzene second in reaction tube The common catalyst system and catalyzing of ketone compounds, 7.5-30mol% cobalts/copper；0.3-1.2mmol cesium salts and 1-6mL solvents；Wherein cobalt/copper is common Catalyst system and catalyzing includes 2.5-10mol%CoCl2With 5-20mol% CuI or CuBr；Cesium salt is Cs2CO3Or CsI；Solvent is first One kind in benzene, dichloroethanes and chlorobenzene；
(2) reaction is stirred under conditions of reaction tube being placed in into 120-140 DEG C in air atmosphere, its stirring reaction time >= 24h；
(3) after completion of the reaction, reaction tube is cooled to room temperature, and reactant mixture is filtered, and is concentrated under conditions of temperature >=50 DEG C, Then post is crossed by column chromatography, uses the mixed solution of ethyl acetate and dichloromethane to be eluted for eluant, eluent, obtained stream Part carries out obtaining the imidazoles [1,2-a after solvent is removed in vacuum distillation:3,4-a'] and two pyridine salt compounds；Its chemical reaction side Formula is：
Wherein, R1For hydrogen, unsubstituted or the alkyl, halogen and the alkoxy that is unsubstituted or being optionally substituted by halogen that are optionally substituted by halogen In one kind；R2For hydrogen, unsubstituted or the alkyl, halogen and the alkoxy that is unsubstituted or being optionally substituted by halogen that are optionally substituted by halogen In one kind；R3For hydrogen, unsubstituted or the alkyl, halogen and the alkoxy that is unsubstituted or being optionally substituted by halogen that are optionally substituted by halogen In one kind；R1Substituting group position is two or three-digit；R2Substituting group position is 9 or 10；R3Substituting group position is 11 or 12 Position.
Embodiment 2
A kind of imidazoles [1,2-a:3,4-a'] and two pyridine salt compounds, its chemical structural formula are：
Above-mentioned imidazoles [1,2-a:3,4-a'] and the chemical equation of two pyridine salt compounds (3aa) be：
Its synthetic method, comprises the following steps：
(1) toward sequentially adding 0.2mmol pyridine radicals pyridone (A1), 0.6mmol bromoacetophenones (A2), 5mol% in reaction tube CoCl2, 10mol%CuI, 0.6mmol Cs2CO3With 2mL solvents, wherein the solvent is toluene；
(2) reaction tube is placed under conditions of 130 DEG C in air atmosphere and is stirred reaction, its stirring reaction time >=24h；
(3) after completion of the reaction, reaction tube is cooled to room temperature, and reactant mixture is filtered, and is concentrated under conditions of temperature >=50 DEG C, Then post is crossed by column chromatography, using the silicagel column of 200-300 mesh, using ethyl acetate and dichloromethane by volume example as 1:1 Mixed solution eluted for eluant, eluent, obtained fraction is carried out under conditions of temperature >=50 DEG C after vacuum distillation removes solvent Compound (3aa) red solid is obtained, 43mg, yield 87%, fusing point is 147-148 DEG C；1H NMR(500MHz, CDCl3):δ 10.43 (d, J=6.7Hz, 1H), 9.57 (d, J=8.8Hz, 1H), 7.79 (t, J=8.1Hz, 1H), 7.59 (m, 2H), 7.54 (m, 2H), 7.46 (d, J=7.4Hz, 2H), 7.22 (t, J=8.5Hz, 1H), 5.99 (d, J=8.8Hz, 1H), 5.53 (d, J=8.8Hz, 1H)13C NMR(125MHz,CDCl3):δ183.0,159.4,140.8,140.4,139.5, 136.3,131.2,130.9,128.9,128.4,127.6,120.6,116.0,109.1,101.8,92.0.HRMS m/z (ESI)Calcd for C18H13N2O2[M+H+],289.0972,found 289.0974。
Embodiment 3
A kind of imidazoles [1,2-a:3,4-a'] and two pyridine salt compounds, its chemical structural formula are：
Above-mentioned imidazoles [1,2-a:3,4-a'] and the chemical equation of two pyridine salt compounds (3ba) be：
Its synthetic method, comprises the following steps：
(1) toward sequentially adding 0.2mmol pyridine radicals pyridine compounds (B1), 0.6mmol bromoacetophenones in reaction tube (A2), 5mol%CoCl2, 10mol%CuI, 0.6mmol Cs2CO3With 2mL solvents, wherein the solvent is toluene；
(2) reaction tube is placed under conditions of 130 DEG C in air atmosphere and is stirred reaction, its stirring reaction time >=24h；
(3) after completion of the reaction, reaction tube is cooled to room temperature, and reactant mixture is filtered, and is concentrated under conditions of temperature >=50 DEG C, Then post is crossed by column chromatography, using the silicagel column of 200-300 mesh, using ethyl acetate and dichloromethane by volume example as 1:1 Mixed solution eluted for eluant, eluent, obtained fraction is carried out under conditions of temperature >=50 DEG C after vacuum distillation removes solvent Compound (3ba) red solid is obtained, 43mg, yield 71%, fusing point is 174-175 DEG C；1H NMR(400MHz, CDCl3):δ 10.56 (d, J=6.7Hz, 1H), 9.66 (d, J=8.9Hz, 1H), 7.86 (t, J=8.3Hz, 1H), 7.66 (t, J =7.2Hz, 2H), 7.61 (t, J=7.9Hz, 2H), 7.55 (t, J=7.2Hz, 2H), 7.26 (d, J=7.9Hz, 1H), 5.58 (d, J=8.1Hz, 1H), 2.26 (s, 3H)13C NMR(100MHz,CDCl3):δ182.4,158.8,140.6,139.1, 139.0,136.1,131.1,130.7,128.9,128.4,127.6,120.7,115.9,111.3,108.7,91.9, 15.9.HRMS m/z(ESI)Calcd for C19H15N2O2[M+H+],303.1128,found 303.1138。
Embodiment 4
A kind of imidazoles [1,2-a:3,4-a'] and two pyridine salt compounds, its chemical structural formula are：
Above-mentioned imidazoles [1,2-a:3,4-a'] and the chemical equation of two pyridine salt compounds (3ca) be：
Its synthetic method, comprises the following steps：
(1) toward sequentially adding 0.2mmol pyridine radicals pyridine compounds (C1), 0.6mmol bromoacetophenones in reaction tube (A2), 5mol%CoCl2, 10mol%CuI, 0.6mmol Cs2CO3With 2mL solvents, wherein the solvent is toluene；
(2) reaction tube is placed under conditions of 130 DEG C in air atmosphere and is stirred reaction, its stirring reaction time >=24h；
(3) after completion of the reaction, reaction tube is cooled to room temperature, and reactant mixture is filtered, and is concentrated under conditions of temperature >=50 DEG C, Then post is crossed by column chromatography, using the silicagel column of 200-300 mesh, using ethyl acetate and dichloromethane by volume example as 1:1 Mixed solution eluted for eluant, eluent, obtained fraction is carried out under conditions of temperature >=50 DEG C after vacuum distillation removes solvent Compound (3ca) red solid is obtained, 52mg, yield 87%, fusing point is 171-172 DEG C；1H NMR(500MHz, CDCl3):δ 10.36 (t, J=8.5Hz, 1H), 9.43 (d, J=8.8Hz, 1H), 7.73 (t, J=8.0Hz, 1H), 7.54 (d, J =7.5Hz, 2H), 7.48 (m, 2H), 7.42 (t, J=7.5Hz, 2H), 5.85 (s, 1H), 5.32 (s, 1H), 1.99 (s, 3H) .13C NMR(125MHz,CDCl3):δ182.8,151.7,140.4,139.9,136.2,131.1,131.0.128.8,128.5, 127.6,120.5,115.7,108.5,102.6,93.8,22.5.HRMS m/z(ESI)Calcd for C19H15N2O2[M+H+],303.1128,found 303.1138。
Embodiment 5
A kind of imidazoles [1,2-a:3,4-a'] and two pyridine salt compounds, its chemical structural formula are：
Above-mentioned imidazoles [1,2-a:3,4-a'] and the chemical equation of two pyridine salt compounds (3ea) be：
Its synthetic method, comprises the following steps：
(1) toward sequentially adding 0.2mmol pyridine radicals pyridine compounds (E1), 0.6mmol bromoacetophenones in reaction tube (A2), 5mol%CoCl2, 10mol%CuI, 0.6mmol Cs2CO3With 2mL solvents, wherein the solvent is toluene；
(2) reaction tube is placed under conditions of 130 DEG C in air atmosphere and is stirred reaction, its stirring reaction time >=24h；
(3) after completion of the reaction, reaction tube is cooled to room temperature, and reactant mixture is filtered, and is concentrated under conditions of temperature >=50 DEG C, Then post is crossed by column chromatography, using the silicagel column of 200-300 mesh, using ethyl acetate and dichloromethane by volume example as 1:1 Mixed solution eluted for eluant, eluent, obtained fraction is carried out under conditions of temperature >=50 DEG C after vacuum distillation removes solvent Compound (3ea) red solid is obtained, 48mg, yield 78%, fusing point is 156-157 DEG C；1H NMR(400MHz, CDCl3):δ 10.52 (d, J=6.7Hz, 1H), 9.63 (d, J=8.8Hz, 1H), 7.88 (ddd, J=8.7,7.4,1.1Hz, 1H), 7.63 (m, 4H), 7.54 (m, 2H), 7.28 (m, 1H), 5.44 (dd, J=8.8,2.9Hz, 1H)13C NMR(100MHz, CDCl3):δ182.6,151.5(d,JC-F=4.0Hz), 142.3,140.5,140.2,137.1,135.9,131.3,130.7, (129.0,128.6,127.6,124.3 d, J=18.9Hz), 121.2,116.0,108.7,99.1 (d, JC-F=4.2Hz), 88.6.HRMS m/z(ESI)Calcd for C18H12FN2O2[M+H+],307.0877,found 307.0877。
Embodiment 6
A kind of imidazoles [1,2-a:3,4-a'] and two pyridine salt compounds, its chemical structural formula are：
Above-mentioned imidazoles [1,2-a:3,4-a'] and the chemical equation of two pyridine salt compounds (3eb) be：
Its synthetic method, comprises the following steps：
(1) toward sequentially adding 0.2mmol pyridine radicals pyridine compounds (E1), 0.6mmol alpha-bromoacetophenones in reaction tube Compound (A3), 5mol%CoCl2, 10mol%CuI, 0.6mmol Cs2CO3With 2mL solvents, wherein the solvent is toluene；
(2) reaction tube is placed under conditions of 130 DEG C in air atmosphere and is stirred reaction, its stirring reaction time >=24h；
(3) after completion of the reaction, reaction tube is cooled to room temperature, and reactant mixture is filtered, and is concentrated under conditions of temperature >=50 DEG C, Then post is crossed by column chromatography, using the silicagel column of 200-300 mesh, using ethyl acetate and dichloromethane by volume example as 1:1 Mixed solution eluted for eluant, eluent, obtained fraction is carried out under conditions of temperature >=50 DEG C after vacuum distillation removes solvent Compound (3eb) red solid is obtained, 57mg, yield 85%, fusing point is 166-167 DEG C；1H NMR(400MHz,CDCl3) δ 10.30 (d, J=6.8Hz, 1H), 9.56 (d, J=8.8Hz, 1H), 7.81-7.73 (m, 1H), 7.64-7.59 (m, 2H), 7.56 (td, J=7.3,1.2Hz, 1H), 7.27 (dd, J=11.1,8.9Hz, 1H), 7.00-6.92 (m, 2H), 5.65 (dd, J =8.9,3.0Hz, 1H), 3.85 (s, 3H)13C NMR(101MHz,CDCl3) δ 182.3,162.5,151.5 (d, J= 29.0Hz), 142.2,139.9,137.0,135.7,132.3,130.3,130.0,128.2,124.4 (d, J=18.9Hz), (121.0,116.1,114.2,109.0,88.5 d, J=5.4Hz), 55.5.HRMS m/z (ESI) Calcd for C19H14FN2O3[M+H+],337.0983,found 337.0985。

Claims (10)

  1. A kind of 1. imidazoles [1,2-a:3,4-a'] and two pyridine salt compounds synthetic method, it is characterised in that including following Step：
    （1）Pyridine radicals pyridine compounds, alpha-bromoacetophenone compound are sequentially added into reaction tube, cobalt/copper is catalyzed altogether System, cesium salt and solvent；
    （2）Reaction is stirred under conditions of reaction tube is placed in into 120-140 DEG C in air atmosphere, its stirring reaction time >= 24h；
    （3）After completion of the reaction, reaction tube is cooled to room temperature, and reactant mixture is filtered, and concentration, then crosses post by column chromatography, The mixed solution of ethyl acetate and dichloromethane is used to be eluted for eluant, eluent, obtained fraction carries out vacuum distillation and removes solvent After obtain imidazoles [1,2-a:3,4-a'] and two pyridine salt compounds；Its chemical equation is：
    Wherein, R1For hydrogen, unsubstituted or the alkyl, halogen and the alkoxy that is unsubstituted or being optionally substituted by halogen that are optionally substituted by halogen In one kind；R2For hydrogen, unsubstituted or the alkyl, halogen and the alkoxy that is unsubstituted or being optionally substituted by halogen that are optionally substituted by halogen In one kind；R3For hydrogen, unsubstituted or the alkyl, halogen and the alkoxy that is unsubstituted or being optionally substituted by halogen that are optionally substituted by halogen In one kind.
  2. A kind of 2. imidazoles [1,2- as claimed in claim 1a:3,4-a'] and two pyridine salt compounds synthetic method, its It is characterised by, catalyst system and catalyzing includes CoCl to described cobalt/copper altogether2And mantoquita, wherein mantoquita is CuI or CuBr；The cesium salt is Cs2CO3Or CsI；The solvent is one kind in toluene, dichloroethanes and chlorobenzene.
  3. A kind of 3. imidazoles [1,2- as claimed in claim 1a:3,4-a'] and two pyridine salt compounds synthetic method, its It is characterised by, step（1）In 0.3-1.2mmol bromoacetophenones are added per 0.1-0.4mmol pyridine radicals pyridine compounds The common catalyst system and catalyzing of class compound, 7.5-30mol% cobalts/copper；0.3-1.2mmol cesium salts and 1-6mL solvents；Wherein cobalt/copper is catalyzed altogether System includes 2.5-10mol% CoCl2With 5-20mol% CuI or CuBr.
  4. A kind of 4. imidazoles [1,2- as claimed in claim 1a:3,4-a'] and two pyridine salt compounds synthetic method, its It is characterised by, step（1）The ratio of the amount of the material of middle pyridine radicals pyridine compounds and cesium salt is：1: 3.
  5. A kind of 5. imidazoles [1,2- as claimed in claim 1a:3,4-a'] and two pyridine salt compounds synthetic method, its It is characterised by, catalyst system and catalyzing includes CoCl to the cobalt/copper altogether2And mantoquita, CoCl2Molar percentage with mantoquita is 1:1-2.5 Wherein mantoquita is CuI or CuBr.
  6. A kind of 6. imidazoles [1,2- as claimed in claim 1a:3,4-a'] and two pyridine salt compounds synthetic method, its It is characterised by, step（1）In per 0.20mmol pyridine radicals pyridones sequentially add 0.60mmol bromoacetophenones, 15mol% cobalts/ The common catalyst system and catalyzing of copper, 0.6mmol Cs2CO3With 2mL toluene；Wherein, catalyst system and catalyzing includes 5mol%CoCl to cobalt/copper altogether2With 10mol%CuI。
  7. A kind of 7. imidazoles [1,2- as claimed in claim 1a:3,4-a'] and two pyridine salt compounds synthetic method, its It is characterised by, step（2）Middle reaction tube is placed in 130oReaction is stirred under conditions of C.
  8. A kind of 8. imidazoles [1,2- as claimed in claim 1a:3,4-a'] and two pyridine salt compounds synthetic method, its It is characterised by, step（3）In concentration process be in temperature >=50oCarried out under conditions of C；Described fraction temperature >= 50oVacuum distillation is carried out under conditions of C and removes solvent.
  9. A kind of 9. imidazoles [1,2- as claimed in claim 1a:3,4-a'] and two pyridine salt compounds synthetic method, its It is characterised by, step（3）Described in the silicagel column for 200-300 mesh that uses of column chromatography；The ethyl acetate and dichloromethane Mixed solution in example ethyl acetate by volume：Dichloromethane=1:1.
  10. A kind of 10. imidazoles [1,2-a as claimed in claim 1:3,4-a'] and two pyridine salt compounds synthetic method, its It is characterised by, the R1Substituting group position is two or three-digit；R2Substituting group position is 9 or 10；R3Substituting group position is 11 Or 12.
CN201710797018.2A 2017-09-06 2017-09-06 A kind of imidazoles [1,2 a:3,4 a '] and two pyridine salt compounds synthetic method Pending CN107739379A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201710797018.2A CN107739379A (en) 2017-09-06 2017-09-06 A kind of imidazoles [1,2 a:3,4 a '] and two pyridine salt compounds synthetic method

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201710797018.2A CN107739379A (en) 2017-09-06 2017-09-06 A kind of imidazoles [1,2 a:3,4 a '] and two pyridine salt compounds synthetic method

Publications (1)

Publication Number Publication Date
CN107739379A true CN107739379A (en) 2018-02-27

Family

ID=61235410

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201710797018.2A Pending CN107739379A (en) 2017-09-06 2017-09-06 A kind of imidazoles [1,2 a:3,4 a '] and two pyridine salt compounds synthetic method

Country Status (1)

Country Link
CN (1) CN107739379A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109678854A (en) * 2019-01-22 2019-04-26 陕西师范大学 A kind of method that manganese catalyzes and synthesizes pyrido [1,2-a] indoles -6 (1H) -one class compound

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103435558A (en) * 2013-09-02 2013-12-11 温州大学 Synthetic method of quinazoline derivative
CN103467388A (en) * 2013-09-02 2013-12-25 温州大学 Method for synthesizing aryl or heteroaryl substituted quinazoline compound
CN106632330A (en) * 2016-10-11 2017-05-10 南阳师范学院 Pyridino-[2', 1': 2, 3]piperidine[1, 6-a]indole salt and compounding method thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103435558A (en) * 2013-09-02 2013-12-11 温州大学 Synthetic method of quinazoline derivative
CN103467388A (en) * 2013-09-02 2013-12-25 温州大学 Method for synthesizing aryl or heteroaryl substituted quinazoline compound
CN106632330A (en) * 2016-10-11 2017-05-10 南阳师范学院 Pyridino-[2', 1': 2, 3]piperidine[1, 6-a]indole salt and compounding method thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
TING LI等: "Cobalt/Copper-Cocatalyzed Synthesis of Imidazo[1,2‑a:3,4‑a’]dipyridiniums from 2H‑[1,2’-Bipyridin]-2-ones and 2‑Bromoacetophenones", 《J. ORG. CHEM.》 *
TING LI等: "Rhodium-Catalyzed/Copper-Mediated Tandem C(sp2)-H Alkynylation and Annulation: Synthesis of 11-Acylated Alkynylation and Annulation: Synthesis of 11-Acylated Imidazo[1,2-a:3,4-a"]dipyridin-5-ium-4-olates...", 《ORG. LETT.》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109678854A (en) * 2019-01-22 2019-04-26 陕西师范大学 A kind of method that manganese catalyzes and synthesizes pyrido [1,2-a] indoles -6 (1H) -one class compound
CN109678854B (en) * 2019-01-22 2021-04-09 陕西师范大学 Method for synthesizing pyrido [1,2-a ] indole-6 (1H) -ketone compound by manganese catalysis

Similar Documents

Publication Publication Date Title
CN102659494B (en) Method for asymmetric synthesis of 3,3-disubstituted-2-oxindole compound
CN106749020B (en) A kind of synthetic method of 3- acyl group quinolines
CN102977017B (en) Method for catalytically preparing 6(5H)-phenanthridine ketone by copper component
Meshram et al. Bismuthtriflate-catalyzed Reaction of N-Alkylisatins with Allyltrimethylsilane
CN105732619A (en) Synthesizing method of 5,6,7,8-tetrahydropyridino-[2,3-d]pyrimidine compound
CN107739379A (en) A kind of imidazoles [1,2 a:3,4 a '] and two pyridine salt compounds synthetic method
CN108752338A (en) A kind of preparation method of 1,2,3 full substitution Indoli zine derivatives
CN108658841A (en) A kind of carbazole compound and preparation method thereof
CN111004234A (en) C3-site halogenation method of 2-phenylimidazo [1,2- α ] pyridine compound
CN108047128A (en) A kind of method for synthesizing (E) -2- methyl 4-phenyl -6- styryl substituted pyridine compounds
CN104876929A (en) Synthesis method and application of 1,2,3,4-tetrahydronaphthyridine compound
CN107629049B (en) Synthesis method of pyridine [2,1-a ] isoindole compound
CN108640914B (en) Method for synthesizing isoindole [2,1-b ] isoquinoline-5, 7-diketone compound
CN107641101A (en) A kind of preparation method of phenanthridines ketone compounds
CN102718694B (en) 3-cyan substituted indole compound and synthetic method thereof
CN107445835B (en) Synthesis method of 1, 2-dihydro cyclobuteno [ a ] naphthalene derivative and precursor thereof
CN101691355B (en) Substituted 4-quinolinone compounds and preparation method thereof
CN106243073B (en) A kind of 2-H 1-benzopyran derivatives and its synthetic method
CN105859557B (en) A kind of preparation method of esters of alpha, beta, unsaturated carboxylic acids compound
CN116640149A (en) Quinoline fused ring compound and preparation method and application thereof
CN109438408A (en) A kind of synthetic method of Dihydroiso-coumarin class compound
CN110590774B (en) Trifluoromethyl imidazole condensed ring compound and preparation method thereof
CN111138346B (en) 2-ethyl-4,6-disubstituted pyridine compound and preparation method thereof
CN113087669B (en) Preparation method of 4-cyano-5-bromopyrimidine
CN110396096B (en) Indole [3,2-c ] coumarin compound and derivative and synthetic method thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20180227