CN109776574A - Bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thio-ether type compounds and its synthetic method - Google Patents
Bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thio-ether type compounds and its synthetic method Download PDFInfo
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- CN109776574A CN109776574A CN201910141780.4A CN201910141780A CN109776574A CN 109776574 A CN109776574 A CN 109776574A CN 201910141780 A CN201910141780 A CN 201910141780A CN 109776574 A CN109776574 A CN 109776574A
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- imidazo
- pyridine
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title claims abstract description 29
- 150000003568 thioethers Chemical class 0.000 title claims abstract description 29
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 title claims description 22
- 238000010189 synthetic method Methods 0.000 title abstract description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims abstract description 34
- -1 sulphur nitrile Chemical class 0.000 claims abstract description 33
- 238000006243 chemical reaction Methods 0.000 claims abstract description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000005864 Sulphur Substances 0.000 claims abstract description 26
- 239000002253 acid Substances 0.000 claims abstract description 24
- 150000002148 esters Chemical class 0.000 claims abstract description 22
- 229910000027 potassium carbonate Inorganic materials 0.000 claims abstract description 17
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims abstract description 16
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 16
- 238000007445 Chromatographic isolation Methods 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 238000000605 extraction Methods 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 78
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 26
- 238000002360 preparation method Methods 0.000 claims description 20
- VNHBYKHXBCYPBJ-UHFFFAOYSA-N 5-ethynylimidazo[1,2-a]pyridine Chemical class C#CC1=CC=CC2=NC=CN12 VNHBYKHXBCYPBJ-UHFFFAOYSA-N 0.000 claims description 13
- 239000003480 eluent Substances 0.000 claims description 13
- GKQOGAMWHPUXJM-UHFFFAOYSA-N 2-(2-bromophenyl)imidazo[1,2-a]pyridine Chemical class BrC1=CC=CC=C1C1=CN(C=CC=C2)C2=N1 GKQOGAMWHPUXJM-UHFFFAOYSA-N 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 6
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 5
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 239000000284 extract Substances 0.000 claims description 3
- 239000004575 stone Substances 0.000 claims description 2
- 239000002585 base Substances 0.000 abstract description 17
- 150000003222 pyridines Chemical class 0.000 abstract description 3
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003513 alkali Substances 0.000 abstract description 2
- 239000003054 catalyst Substances 0.000 abstract description 2
- 150000005234 imidazo[1,2-a]pyridines Chemical class 0.000 abstract description 2
- 229910052751 metal Inorganic materials 0.000 abstract description 2
- 239000002184 metal Substances 0.000 abstract description 2
- 238000007259 addition reaction Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 44
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 230000008901 benefit Effects 0.000 description 11
- 238000010828 elution Methods 0.000 description 11
- 239000003208 petroleum Substances 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- LMTCUTLBCVWIFS-UHFFFAOYSA-N 2-(2-bromophenyl)-1h-imidazole Chemical class BrC1=CC=CC=C1C1=NC=CN1 LMTCUTLBCVWIFS-UHFFFAOYSA-N 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N methylimidazole Natural products CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- MMPMPNYEMKILJC-UHFFFAOYSA-N n-[2-(4-methylphenyl)-3-phenyl-1,2,4-thiadiazol-5-ylidene]-n'-phenylbenzenecarboximidamide Chemical compound C1=CC(C)=CC=C1N(S1)C(C=2C=CC=CC=2)=NC1=NC(C=1C=CC=CC=1)=NC1=CC=CC=C1 MMPMPNYEMKILJC-UHFFFAOYSA-N 0.000 description 2
- NNGXNALKPNFUQS-UHFFFAOYSA-N 2-(2-bromophenyl)pyridine Chemical compound BrC1=CC=CC=C1C1=CC=CC=N1 NNGXNALKPNFUQS-UHFFFAOYSA-N 0.000 description 1
- IIOKDOJKJGCOEP-UHFFFAOYSA-N 3h-pyrrolo[1,2-a]imidazole Chemical compound C1=CN2CC=NC2=C1 IIOKDOJKJGCOEP-UHFFFAOYSA-N 0.000 description 1
- MEJAPGGFIJZHEJ-UHFFFAOYSA-N 5-acetamido-1,3,4-thiadiazole-2-sulfonyl chloride Chemical compound CC(=O)NC1=NN=C(S(Cl)(=O)=O)S1 MEJAPGGFIJZHEJ-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- NEFCYWWPVICWNJ-UHFFFAOYSA-N [N+]1(=CNC2=C1C=CC=N2)[S-] Chemical class [N+]1(=CNC2=C1C=CC=N2)[S-] NEFCYWWPVICWNJ-UHFFFAOYSA-N 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- UVNXNSUKKOLFBM-UHFFFAOYSA-N imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=CSC2=NC=CN21 UVNXNSUKKOLFBM-UHFFFAOYSA-N 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000007342 radical addition reaction Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of bis- (2-(imidazo [1,2-a] pyridine -2- base) phenyl) thio-ether type compounds and its synthetic method, include the following steps: under air environment, by 2-(2- bromophenyl) imidazo [1,2-a] with different sulphur nitrile acid phenenyl ester addition reaction tube, then addition cuprous iodide, potassium carbonate are added solvent, react 12 hours at 120 DEG C pyridine compounds and their；After reaction extraction, chromatographic isolation, be dried to obtain target product.Using cheap metal copper (I) as catalyst, potassium carbonate is alkali for the reaction, and n,N-Dimethylformamide realizes imidazo [1,2- as reaction dissolventa] pyridine compounds react with different the disulfide-bridged of sulphur nitrile acid phenenyl ester, this method will be to imidazo [1,2-a] pyridine compounds disulfide-bridged reaction research and application be of great significance.
Description
Technical field
The invention belongs to organic compound synthesis and applied technical fields, and in particular to a kind of bis- (2- (imidazos [1,2-
A] pyridine -2- base) phenyl) thio-ether type compounds and its synthetic method.
Background technique
Pyridine-imidazole is a kind of extremely important and common nitrogen heterocyclic (Comprehensive
Heterocyclic Chemistry III), derivative is very widely used in terms of natural products and pharmaceutical chemistry.
(Elsevier:Oxford,2008,11,409-499.；Med.Chem.2007,7,888.；Med.Chem.2015,23,6087-
6099.；J.Org.Chem.2012,77,5552-5558；J.Med.Chem.2015,58,8529；).C-S key is constructed in life
The application of object, drug and synthesis etc. has potential value, at the same time, mercaptan, disulphide, sulfonic acid, sulfohydrazide,
Sodium sulfonate, DMSO etc. can be used as sulfiding reagent to obtain imidazopyridine sulfide derivative.
Different sulphur nitrile acid phenenyl ester is very widely used in organic synthesis, has synthesized one by nucleophilic addition or free radical addition
Series heterocyclic compound and amides compound (Chem.Commun., 2016,52,8444；J.Org.Chem.2018,83,
4375；ACS Catal.2012,2,544-551；Green Chem.,2017,19,2092).This reaction is for the first time with different sulphur nitrile acid
Phenyl ester is the disulfide-bridged reaction that sulfiding reagent realizes double c h bonds using simple reaction system.This method is for different sulphur nitrile acid
The research of reaction and the application of phenyl ester will be significant.Bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thioethers have
Potential medical value, exploitation is of great significance and bright market prospects.
Summary of the invention
The object of the present invention is to provide a kind of bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thio-ether type compounds
And its synthetic method, this method is simple and easy, low in cost and be easy to purify.
To achieve the above object, the invention adopts the following technical scheme:
A kind of bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thio-ether type compounds, general structure are as follows:
Wherein R1For hydrogen, alkyl, alkoxy, halogen etc.；Het is pyridine, isoquinolin or thiazole etc..
The preparation method of bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thio-ether type compounds, including under
It states step: under air environment, 2- (2- bromophenyl) imidazo [1,2-a] pyridine compounds and their and different sulphur nitrile acid phenenyl ester being added
In reaction tube, cuprous iodide is added, potassium carbonate is then added, is eventually adding solvent, is reacted 12 hours at 120 DEG C；Reaction terminates
After extract, after extraction completely, by chromatographic isolation after organic phase concentrated by rotary evaporation, be dried to obtain target product, reaction equation is as follows:
The general formula of 2- (2- bromophenyl) imidazo [1,2-a] pyridine compounds and their are as follows:
The general structure of different sulphur nitrile acid phenenyl ester are as follows:
Wherein R1For hydrogen, alkyl, alkoxy, halogen etc.；Het is pyridine, isoquinolin or thiazole etc..
The mass ratio of the material of 2- (2- bromophenyl) imidazo [1,2-a] pyridine compounds and their and different sulphur nitrile acid phenenyl ester is
1:1~1.5.
The dosage of the cuprous iodide is the amount of the substance of 2- (2- bromophenyl) imidazo [1,2-a] pyridine compounds and their
0.1~0.2 times.
The dosage of the potassium carbonate is the amount 1~2 of the substance of 2- (2- bromophenyl) imidazo [1,2-a] pyridine compounds and their
Times.
Preferably, the solvent n,N-Dimethylformamide, with 0.2mmol 2- (2- bromophenyl) imidazo [1,2-a]
On the basis of the amount of the substance of pyridine compounds and their, the dosage of the solvent is 2mL.
Preferably, the extractant used that extracts is ethyl acetate.
Preferably, the eluant, eluent that the chromatographic isolation uses is the ethyl acetate and stone of 0~100:100~0 for volume ratio
Oily ether.
Preferably, reaction temperature is 120 DEG C, reaction time 12h.
Beneficial effects of the present invention: the present invention is to synthesize bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thioether classes
Compound provides a kind of easy-to-use method.Using cheap metal copper (I) as catalyst, potassium carbonate is alkali for the reaction,
N,N-Dimethylformamide realizes the sulphur of imidazo [1,2-a] pyridine compounds Yu different sulphur nitrile acid phenenyl ester as reaction dissolvent
Bridging reaction.This method is simple and efficient, low in cost and be easy to purify, and enriches imidazo [1,2-a] pyridine compounds sulphur bridge
The even type of reaction, while also achieving the new reactive mode of different sulphur nitrile acid phenenyl ester.This method will be to imidazo [1,2-a] pyrrole
The research and application of the disulfide-bridged reaction of acridine compound are of great significance.
Specific embodiment
Combined with specific embodiments below, the present invention will be further described.It should be understood that following embodiment is merely to illustrate this
The person skilled in the art of the range of invention and is not intended to limit the present invention, the field can make one according to the content of foregoing invention
A little nonessential modifications and adaptations.
Embodiment 1
The structural formula of bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thioethers of the compound of the present embodiment are as follows:
The preparation method comprises the following steps: 2- (2- bromophenyl) imidazoles of 0.2mmol is added into 10mL Shrek pipe under air environment
And [1,2-a] pyridine compounds, the different sulphur nitrile acid phenenyl ester of 0.3mmol, the cuprous iodide of 0.02mmol, 0.4mmol potassium carbonate, N,
Dinethylformamide 2mL, 120 DEG C are reacted 12 hours；After reaction, benefit is extracted with ethyl acetate, chromatography after reduced pressure
It separates (silica gel 200-300 mesh, eluant, eluent: ethyl acetate/petroleum ether gradient elution, ratio is by 0/100 to 100/0), dry
Faint yellow solid, yield 89%.mp 251–252℃；1H NMR(400MHz,CDCl3)δ8.12–8.10(m,4H),7.63–
7.60 (m, 4H), 7.58-7.55 (m, 4H), 7.50 (d, J=8.9Hz, 2H), 7.11-7.07 (m, 2H), 6.34 (td, J=
6.9,1.0Hz,2H).13C NMR(101MHz,CDCl3)δ150.9,146.6,133.8,129.6,128.9,128.6,126.3,
125.4,117.4,112.6,107.5.HRMS(positive ESI):[M+H]+calcd for C26H18N4S+:419.1325,
found:419.1324.
Embodiment 2
The structural formula of bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thioethers of the compound of the present embodiment are as follows:
The preparation method comprises the following steps: 2- (2- bromophenyl) imidazoles of 0.2mmol is added into 10mL Shrek pipe under air environment
And [1,2-a] pyridine compounds, the different sulphur nitrile acid phenenyl ester of 0.2mmol, the cuprous iodide of 0.02mmol, 0.4mmol potassium carbonate, N,
Dinethylformamide 2mL, 120 DEG C are reacted 12 hours；After reaction, benefit is extracted with ethyl acetate, chromatography after reduced pressure
It separates (silica gel 200-300 mesh, eluant, eluent: ethyl acetate/petroleum ether gradient elution, ratio is by 0/100 to 100/0), dry
Faint yellow solid, yield 56%.mp 251–252℃；1H NMR(400MHz,CDCl3)δ8.12–8.10(m,4H),7.63–
7.60 (m, 4H), 7.58-7.55 (m, 4H), 7.50 (d, J=8.9Hz, 2H), 7.11-7.07 (m, 2H), 6.34 (td, J=
6.9,1.0Hz,2H).13C NMR(101MHz,CDCl3)δ150.9,146.6,133.8,129.6,128.9,128.6,126.3,
125.4,117.4,112.6,107.5.HRMS(positive ESI):[M+H]+calcd for C26H18N4S+:419.1325,
found:419.1324.
Embodiment 3
The structural formula of bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thioethers of the compound of the present embodiment are as follows:
The preparation method comprises the following steps: 2- (2- bromophenyl) imidazoles of 0.2mmol is added into 10mL Shrek pipe under air environment
And [1,2-a] pyridine compounds, the different sulphur nitrile acid phenenyl ester of 0.3mmol, the cuprous iodide of 0.01mmol, 0.4mmol potassium carbonate, N,
Dinethylformamide 2mL, 120 DEG C are reacted 12 hours；After reaction, benefit is extracted with ethyl acetate, chromatography after reduced pressure
It separates (silica gel 200-300 mesh, eluant, eluent: ethyl acetate/petroleum ether gradient elution, ratio is by 0/100 to 100/0), dry
Faint yellow solid, yield 63%.mp 251–252℃；1H NMR(400MHz,CDCl3)δ8.12–8.10(m,4H),7.63–
7.60 (m, 4H), 7.58-7.55 (m, 4H), 7.50 (d, J=8.9Hz, 2H), 7.11-7.07 (m, 2H), 6.34 (td, J=
6.9,1.0Hz,2H).13C NMR(101MHz,CDCl3)δ150.9,146.6,133.8,129.6,128.9,128.6,126.3,
125.4,117.4,112.6,107.5.HRMS(positive ESI):[M+H]+calcd for C26H18N4S+:419.1325,
found:419.1324.
Embodiment 4
The structural formula of bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thioethers of the compound of the present embodiment are as follows:
The preparation method comprises the following steps: 2- (2- bromophenyl) imidazoles of 0.2mmol is added into 10mL Shrek pipe under air environment
And [1,2-a] pyridine compounds, the different sulphur nitrile acid phenenyl ester of 0.3mmol, the cuprous iodide of 0.02mmol, 0.2mmol potassium carbonate, N,
Dinethylformamide 2mL, 120 DEG C are reacted 12 hours；After reaction, benefit is extracted with ethyl acetate, chromatography after reduced pressure
It separates (silica gel 200-300 mesh, eluant, eluent: ethyl acetate/petroleum ether gradient elution, ratio is by 0/100 to 100/0), dry
Faint yellow solid, yield 69%.mp 251–252℃；1H NMR(400MHz,CDCl3)δ8.12–8.10(m,4H),7.63–
7.60 (m, 4H), 7.58-7.55 (m, 4H), 7.50 (d, J=8.9Hz, 2H), 7.11-7.07 (m, 2H), 6.34 (td, J=
6.9,1.0Hz,2H).13C NMR(101MHz,CDCl3)δ150.9,146.6,133.8,129.6,128.9,128.6,126.3,
125.4,117.4,112.6,107.5.HRMS(positive ESI):[M+H]+calcd for C26H18N4S+:419.1325,
found:419.1324.
Embodiment 5
The structural formula of bis- (2- (6- methylimidazole [1,2-a] pyridine -2- base) phenyl) thioethers of the compound of the present embodiment are as follows:
The preparation method comprises the following steps: 2- (2- bromophenyl) -6- of 0.2mmol is added into 10mL Shrek pipe under air environment
Methylimidazole simultaneously [1,2-a] pyridine compounds, the different sulphur nitrile acid phenenyl ester of 0.3mmol, the cuprous iodide of 0.02mmol, 0.4mmol
Potassium carbonate, n,N-Dimethylformamide 2mL, 120 DEG C are reacted 12 hours；After reaction, benefit is extracted with ethyl acetate, and depressurizes dense
(silica gel 200-300 mesh, eluant, eluent: ethyl acetate/petroleum ether gradient elution, ratio is by 0/100 to 100/ for chromatographic isolation after contracting
0), dry faint yellow solid, yield 74%.mp 72–73℃；1H NMR(400MHz,CDCl3) δ 8.8 (dd, J=7.8,
1.3Hz, 2H), 7.98 (s, 2H), 7.79 (s, 2H), 7.50 (d, J=9.2Hz, 2H), 7.38-7.34 (m, 2H), 7.29-7.27
(m, 2H), 7.22-7,17 (m, 2H), 6.98 (dd, J=9.2,1.5Hz, 2H), 2.25 (s, 3H)13C NMR(101MHz,
CDCl3)δ143.6,142.6,135.5,133.0,132.7,130.7,128.3,127.9,127.6,123.6,121.8,
116.6,112.2,18.1.HRMS(positive ESI):[M+H]+calcd for C28H22N4S+:447.1638,found:
447.1643.
Example 6
The structural formula of bis- (2- (7- methylimidazole [1,2-a] pyridine -2- base) phenyl) thioethers of the compound of the present embodiment are as follows:
The preparation method comprises the following steps: 2- (2- bromophenyl) -7- of 0.2mmol is added into 10mL Shrek pipe under air environment
Methylimidazole simultaneously [1,2-a] pyridine compounds, the different sulphur nitrile acid phenenyl ester of 0.3mmol, the cuprous iodide of 0.02mmol, 0.4mmol
Potassium carbonate, n,N-Dimethylformamide 2mL, 120 DEG C are reacted 12 hours；After reaction, benefit is extracted with ethyl acetate, and depressurizes dense
(silica gel 200-300 mesh, eluant, eluent: ethyl acetate/petroleum ether gradient elution, ratio is by 0/100 to 100/ for chromatographic isolation after contracting
0), dry brown solid, yield 75%.mp 76–77℃；1H NMR(400MHz,CDCl3) δ 8.17 (dd, J=7.9,
1.4Hz, 2H), 7.99 (s, 2H), 7.91 (d, J=6.9,2H), 7.37-7.33 (m, 4H), 7.29-7.26 (m, 2H), 7.21-
7.17 (m, 2H), 6.55 (dd, J=6.9,1.5Hz, 2H), 2.37 (s, 6H)13C NMR(101MHz,CDCl3)δ145.0,
142.6,135.6,135.5,133.1,132.7,130.7,128.3,127.6,125.1,115.7,114.9,111.8,
21.4.HRMS(positive ESI):[M+H]+Calcd.For C28H22N4S+:447.1638,Found:447.1644.
Embodiment 7
The structural formula of bis- (2- (7- methoxyl group imidazoles [1,2-a] pyridine -2- base) phenyl) thioethers of the compound of the present embodiment
Are as follows:
The preparation method comprises the following steps: 2- (2- bromophenyl) -7- of 0.2mmol is added into 10mL Shrek pipe under air environment
Methoxyl group imidazo [1,2-a] pyridine compounds, the different sulphur nitrile acid phenenyl ester of 0.3mmol, the cuprous iodide of 0.02mmol,
0.4mmol potassium carbonate, n,N-Dimethylformamide 2mL, 120 DEG C are reacted 12 hours；After reaction, extracted using ethyl acetate
It takes, (silica gel 200-300 mesh, eluant, eluent: ethyl acetate/petroleum ether gradient elution, ratio is by 0/ for chromatographic isolation after reduced pressure
100 to 100/0), dry faint yellow solid, yield 63%.mp 85–86℃；1H NMR(600MHz,CDCl3)δ8.18(d,J
=7.9Hz, 2H), 7.93 (s, 2H), 7.85 (d, J=7.5Hz, 1H), 7.35 (t, J=7.5Hz, 2H), 7.27 (d, J=
7.5Hz, 1H), 7.20-7.18 (m, 2H), 6.88 (s, 2H), 6.45 (dd, J=7.4,2.2Hz, 2H), 3.84 (s, 6H)13C
NMR(151MHz,CDCl3)δ158.0,146.0,142.4,135.3,132.9,132.7,130.5,128.2,127.6,
126.3,111.3,107.5,94.4,55.5.HRMS(positive ESI):[M+H]+calcd for C28H22N4O2S+:
479.1536,found:479.1541.
Embodiment 8
The structural formula of bis- (2- (7- chlorine imidazoles [1,2-a] pyridine -2- base) phenyl) thioethers of the compound of the present embodiment are as follows:
The preparation method comprises the following steps: 2- (2- bromophenyl) -7- of 0.2mmol is added into 10mL Shrek pipe under air environment
Chlorine imidazo [1,2-a] pyridine compounds, the different sulphur nitrile acid phenenyl ester of 0.3mmol, the cuprous iodide of 0.02mmol, 0.4mmol carbon
Sour potassium, n,N-Dimethylformamide 2mL, 120 DEG C are reacted 12 hours；After reaction, benefit is extracted with ethyl acetate, and is concentrated under reduced pressure
Chromatographic isolation (silica gel 200-300 mesh, eluant, eluent: ethyl acetate/petroleum ether gradient elution, ratio is by 0/100 to 100/0) afterwards,
Dry brown solid, yield 77%.mp 203–204℃；1H NMR(600MHz,CDCl3) δ 8.12 (d, J=7.8Hz, 2H),
8.10 (s, 2H), 8.00 (s, 2H), 7.56 (d, J=9.5Hz, 2H), 7.37 (t, J=7.5Hz, 2H), 7.29 (d, J=
7.9Hz, 2H), 7.23 (t, J=7.5Hz, 2H), 7.12 (d, J=9.5Hz, 2H)13C NMR(151MHz,CDCl3)δ144.0,
142.9,134.9,133.2,132.9,130.8,128.8,127.8,126.2,123.6,120.5,117.8,112.7.HRMS
(positive ESI):[M+H]+calcd for C26H16Cl2N4S+:487.0545,found:487.0550.
Embodiment 9
The structural formula of bis- (2- (imidazo [2, the 1- β] thiazole -6- base) phenyl) thioethers of the compound of the present embodiment are as follows:
The preparation method comprises the following steps: 6- (2- bromophenyl) imidazoles of 0.2mmol is added into 10mL Shrek pipe under air environment
And [2,1- β] thiazolium compounds, the different sulphur nitrile acid phenenyl ester of 0.3mmol, the cuprous iodide of 0.02mmol, 0.4mmol potassium carbonate, N,
Dinethylformamide 2mL, 120 DEG C are reacted 12 hours；After reaction, benefit is extracted with ethyl acetate, chromatography after reduced pressure
It separates (silica gel 200-300 mesh, eluant, eluent: ethyl acetate/petroleum ether gradient elution, ratio is by 0/100 to 100/0), dry
Faint yellow solid, yield 53%.mp 230–231℃；1H NMR(600MHz,CDCl3) δ 8.10 (dd, J=7.8,1.0Hz,
2H), 7.97 (s, 2H), 7.37 (d, J=4.3Hz, 2H), 7.35-7.33 (m, 2H), 7.25-7.24 (m, 2H), 7.19-7.16
(m, 2H), 6.79 (d, J=4.5Hz, 2H)13C NMR(151MHz,CDCl3)δ149.2,144.9,135.5,132.6,
132.2,130.1,128.0,127.6,118.7,112.5,112.4.HRMS(positive ESI):[M+H]+calcd for
C22H14N4S3 +:431.0453,found:431.0454.
Embodiment 10
The structural formula of bis- (2- (imidazo [1,2- β] isoquinolin-2-yl) phenyl) thioethers of the compound of the present embodiment are as follows:
The preparation method comprises the following steps: 2- (2- bromophenyl) imidazoles of 0.2mmol is added into 10mL Shrek pipe under air environment
And [1,2- β] isoquinoline compound, the different sulphur nitrile acid phenenyl ester of 0.3mmol, the cuprous iodide of 0.02mmol, 0.4mmol potassium carbonate,
N,N-Dimethylformamide 2mL, 120 DEG C are reacted 12 hours；After reaction, benefit is extracted with ethyl acetate, color after reduced pressure
Spectrum separation (silica gel 200-300 mesh, eluant, eluent: ethyl acetate/petroleum ether gradient elution, ratio is by 0/100 to 100/0), it is dry
Obtain faint yellow solid, yield 64%.mp 209–210℃；1H NMR(600MHz,CDCl3) δ 8.57 (s, 2H), 8.27 (d, J=
7.0Hz, 2H), 7.74 (d, J=7.9Hz, 2H), 7.70 (d, J=7.5Hz, 2H), 7.54 (d, J=8.9Hz, 2H), 7.49 (t,
J=7.2Hz, 2H), 7.44 (d, J=9.4Hz, 2H), 7.39-7.35 (m, 6H), 7.24 (d, J=7.2Hz, 2H)13C NMR
(101MHz,CDCl3)δ143.0,142.1,135.2,133.0,132.8,132.6,130.6,128.9,128.8,128.3,
127.8,126.4,124.6,123.3,116.9,115.4,111.2.HRMS(positive ESI):[M+H]+calcd for
C34H22N4S+:519.1638,found:519.1643.
Embodiment 11
The structural formula of bis- (2- (2 '-pyridyl group) phenyl) thioethers of the compound of the present embodiment are as follows:
Preparation method: under air environment, 2- (2- bromophenyl) pyridine of 0.2mmol is added into 10mL Shrek pipe
Close object, the different sulphur nitrile acid phenenyl ester of 0.3mmol, the cuprous iodide of 0.02mmol, 0.4mmol potassium carbonate, n,N-Dimethylformamide
2mL, 120 DEG C are reacted 12 hours；After reaction, benefit is extracted with ethyl acetate, chromatographic isolation (silica gel 200- after reduced pressure
300 mesh, eluant, eluent: ethyl acetate/petroleum ether gradient elution, ratio is by 0/100 to 100/0), dry faint yellow solid produces
Rate 95%.mp 77–78℃；1H NMR(400MHz,CDCl3) δ 8.58-8.57 (m, 2H), 7.54 (td, J=7.7,1.8Hz,
2H), 7.45 (dd, J=7.5,1.7Hz, 2H), 7.40 (d, J=7.8Hz, 2H), 7.29-7.25 (m, 2H), 7.24-7.17
(m,,4H),7.13–7.09(m,,4H).13C NMR(101MHz,CDCl3)δ158.0,149.0,142.0,135.7,135.1,
132.9,130.4,129.0,127.1,124.1,121.9.HRMS(positive ESI):[M+H]+calcd for
C22H16N2S+:341.1107,found:341.1111.
Basic principles and main features and advantages of the present invention of the invention have been shown and described above.The skill of the industry
Art personnel it should be appreciated that the present invention is not limited to the above embodiments, the above embodiments and description only describe
The principle of the present invention, without departing from the spirit and scope of the present invention, various changes and improvements may be made to the invention, these
Changes and improvements all fall within the protetion scope of the claimed invention.The claimed scope of the invention by appended claims and
Its equivalent thereof.
Claims (9)
1. a kind of bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thio-ether type compounds, general structure are as follows:
Wherein R1For hydrogen, alkyl, alkoxy, halogen etc.；Het is pyridine, isoquinolin or thiazole.
2. the preparation of bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thio-ether type compounds according to claim 1
Method, it is characterised in that include the following steps: under air environment, by 2- (2- bromophenyl) imidazo [1,2-a] pyridines
It closes object and different sulphur nitrile acid phenenyl ester to be added in reaction tube, cuprous iodide is added, potassium carbonate is then added, be eventually adding solvent, 120 DEG C
Lower reaction 12 hours；After reaction extraction, chromatographic isolation, be dried to obtain target product, reaction equation is as follows:
3. the preparation of bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thio-ether type compounds according to claim 2
Method, it is characterised in that: the general formula of 2- (2- bromophenyl) imidazo [1, the 2-a] pyridine compounds and their are as follows:
The general structure of different sulphur nitrile acid phenenyl ester are as follows:
Wherein R1For hydrogen, alkyl, alkoxy, halogen etc.；Het is pyridine, isoquinolin or thiazole.
4. the preparation of bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thio-ether type compounds according to claim 2
Method, it is characterised in that: the substance of 2- (2- bromophenyl) imidazo [1, the 2-a] pyridine compounds and their and different sulphur nitrile acid phenenyl ester
Amount ratio be 1:1~1.5.
5. the preparation of bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thio-ether type compounds according to claim 2
Method, it is characterised in that: the dosage of the cuprous iodide is the object of 2- (2- bromophenyl) imidazo [1,2-a] pyridine compounds and their
0.1~0.2 times of the amount of matter.
6. the preparation of bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thio-ether type compounds according to claim 2
Method, it is characterised in that: the dosage of the potassium carbonate is the substance of 2- (2- bromophenyl) imidazo [1,2-a] pyridine compounds and their
1~2 times of amount.
7. the preparation of bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thio-ether type compounds according to claim 2
Method, it is characterised in that: the solvent be n,N-Dimethylformamide, with 0.2mmol 2- (2- bromophenyl) imidazo [1,
2-a] pyridine compounds and their substance amount on the basis of, the dosage of the solvent is 2mL.
8. the preparation of bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thio-ether type compounds according to claim 2
Method, it is characterised in that: the extractant used that extracts is ethyl acetate.
9. the preparation of bis- (2- (imidazo [1,2-a] pyridine -2- base) phenyl) thio-ether type compounds according to claim 2
Method, it is characterised in that: the eluant, eluent that the chromatographic isolation uses is the ethyl acetate and stone of 0~100:100~0 for volume ratio
Oily ether.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107663209A (en) * | 2017-09-14 | 2018-02-06 | 郑州大学 | 2 phenyl 3 (benzenesulfonyl) imidazo [1,2 a] pyridine compounds and theirs and its synthetic method |
| CN108997337A (en) * | 2018-08-10 | 2018-12-14 | 郑州大学 | N- (2- heterocyclic base imidazo heteroaromatic -3- base) dibenzenesulfonimide class compound and its synthetic method |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107663209A (en) * | 2017-09-14 | 2018-02-06 | 郑州大学 | 2 phenyl 3 (benzenesulfonyl) imidazo [1,2 a] pyridine compounds and theirs and its synthetic method |
| CN108997337A (en) * | 2018-08-10 | 2018-12-14 | 郑州大学 | N- (2- heterocyclic base imidazo heteroaromatic -3- base) dibenzenesulfonimide class compound and its synthetic method |
Non-Patent Citations (3)
| Title |
|---|
| JUN-RONG ZHANG等: "Metal-Free Thiolation of Imidazopyridines with Functionalized Haloalkanes Using Elemental Sulfur", 《ADV. SYNTH. CATAL.》 * |
| MIO MATSUMURA等，: "Copper-catalyzed tandem cyclization of 2-(2-iodophenyl)imidazo[1,2-a]pyridine derivatives with selenium: Synthesis of benzo[b]selenophenefused imidazo[1,2-a]pyridines", 《TETRAHEDRON LETTERS》 * |
| S. M. ABDUL SHAKOOR等: "Solvent-Driven Iodine-Mediated Oxidative Strategies for the Synthesis of Bis(imidazo[1,2-a]pyridin-3-yl)sulfanes and Disulfanes", 《CHEM. ASIAN J.》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115028641A (en) * | 2022-07-19 | 2022-09-09 | 湖南大学 | Method for synthesizing 5, 8-bifunctional substituted imidazo [1,2-a ] pyrazine compound by cobalt catalysis |
| CN115028641B (en) * | 2022-07-19 | 2024-05-28 | 湖南大学 | Method for synthesizing 5, 8-difunctional substituted imidazo [1,2-a ] pyrazine compound by cobalt catalysis |
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