CN106045914B - A kind of synthetic method of tri-substituted imidazoles - Google Patents
A kind of synthetic method of tri-substituted imidazoles Download PDFInfo
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- -1 tri-substituted imidazoles Chemical class 0.000 title claims abstract description 36
- 238000010189 synthetic method Methods 0.000 title claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 8
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910001958 silver carbonate Inorganic materials 0.000 claims abstract description 5
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 claims abstract description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- PAJALBWYDSQWAV-UHFFFAOYSA-N 1-isocyanosulfonyl-4-methylbenzene Chemical compound CC1=CC=C(S(=O)(=O)[N+]#[C-])C=C1 PAJALBWYDSQWAV-UHFFFAOYSA-N 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 238000001514 detection method Methods 0.000 claims description 2
- 239000003480 eluent Substances 0.000 claims description 2
- 238000003760 magnetic stirring Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 239000003208 petroleum Substances 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- 238000010898 silica gel chromatography Methods 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 239000000758 substrate Substances 0.000 claims description 2
- 238000005292 vacuum distillation Methods 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
- UVXCIFWBXFTMOD-UHFFFAOYSA-N 1-bromo-4-isocyanobenzene Chemical compound BrC1=CC=C([N+]#[C-])C=C1 UVXCIFWBXFTMOD-UHFFFAOYSA-N 0.000 claims 1
- 150000002527 isonitriles Chemical class 0.000 abstract description 20
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 abstract description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 abstract description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 abstract description 6
- 239000002904 solvent Substances 0.000 abstract description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 abstract description 4
- 239000003054 catalyst Substances 0.000 abstract description 4
- 125000000524 functional group Chemical group 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 abstract description 2
- 230000003197 catalytic effect Effects 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- 150000002460 imidazoles Chemical class 0.000 description 12
- 238000001228 spectrum Methods 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 238000000034 method Methods 0.000 description 7
- 238000007363 ring formation reaction Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 125000004423 acyloxy group Chemical group 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 150000003851 azoles Chemical class 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 238000006736 Huisgen cycloaddition reaction Methods 0.000 description 2
- 238000006352 cycloaddition reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- ZRKSVHFXTRFQFL-UHFFFAOYSA-N isocyanomethane Chemical compound C[N+]#[C-] ZRKSVHFXTRFQFL-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 229940122904 Glucagon receptor antagonist Drugs 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 150000004705 aldimines Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000012612 commercial material Substances 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 1
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical compound [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 description 1
- 229940112669 cuprous oxide Drugs 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 239000002608 ionic liquid Substances 0.000 description 1
- RIWNFZUWWRVGEU-UHFFFAOYSA-N isocyanomethylbenzene Chemical group [C-]#[N+]CC1=CC=CC=C1 RIWNFZUWWRVGEU-UHFFFAOYSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- RCIBIGQXGCBBCT-UHFFFAOYSA-N phenyl isocyanide Chemical compound [C-]#[N+]C1=CC=CC=C1 RCIBIGQXGCBBCT-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/84—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention belongs to technical field of organic synthetic chemistry, and the present invention relates to a kind of synthetic methods for synthesizing tri-substituted imidazoles in silver carbonate catalytic one-stage from raw material isonitrile simple and easy to get.In certain reaction temperature and solvent, tri-substituted imidazoles are prepared by aryl isonitrile and functional group's isonitrile.Under nitrogen protection, use silver carbonate as catalyst, reaction temperature is 80 °C.Solvent can choose methylene chloride, Isosorbide-5-Nitrae-dioxane, tetrahydrofuran, dimethyl sulfoxide, wherein best with Isosorbide-5-Nitrae-dioxane.The present invention have it is easy to operate, raw materials and reagents are easy to get, mild condition, the easily separated purifying of product, trisubstituted glyoxaline compound can be made efficiently, in high yield especially suitable for large-scale industrial production suitable for synthesizing various polysubstituted glyoxaline compounds.
Description
Technical field
The invention belongs to technical field of organic synthetic chemistry, and in particular to a kind of one-step synthesis tri-substituted imidazoles
Method.
Technical background
Imidazoles is a kind of important heterocyclic compound, is many bioactive natural products, drug molecule and function material
The key structural elements of material.The pharmacophoric group important as one kind of drug molecule, imidazoles has extensive treatment use, such as anti-
Cancer, anti-HIV be viral, antibacterial, anti-inflammatory, antiallergy, glucagon receptor antagonist etc. are other medicinal.In addition, imidazoles is in conduct
The ligand of metalloenzyme and transition-metal catalyst, organic reaction catalyst, supramolecular chemistry reaction in receiver, ionic liquid
Body, natural products synthesis in terms of play a key role.Since polysubstituted imidazoles is in the extensive of pharmaceutical chemistry and other field
Using, the research of synthetic method be constantly subjected to the attention of people (Med. Res. Rev.2014, 34, 340; J. Med. Chem.1998, 41, 4744; Nature1994, 372, 739.).
The method of synthesis imidazoles has very much, common such as 1) Bredereck imidazoles synthetic method, with α-diketone or Alpha-hydroxy
Ketone and formamide condensation and cyclization obtain substituted imidazoles, 2) alkali promotes p-toluenesulfonyl methyl isocyanide and aldimine or Asia
The cyclization reaction of amine acyl chlorides.Up to the present, [3+2] cycloaddition reaction of transition metal-catalyzed isonitrile and isonitrile directly synthesizes miaow
The report of azole compounds only has 3.It is the dimerization cyclization method of the silver catalysis isonitrile of Grigg seminar report respectively,
Yamamoto seminar cuprous oxide/triphenyl phosphine catalyst aryl isonitrile and methyl isocyanide cycloaddition reaction of intersecting, and
Hong seminar makees catalyst using NHC- copper and isonitrile range is expanded to phenyl isonitrile.However, the production of this three report synthesis
Object is all 1,4- disubstituted imidazole.
[3+2] cycloaddition reaction of aryl isonitrile and isonitrile is the side of an easy synthesis tri-substituted imidazoles
Method, and be to be directly obtained for the first time by 1,2- migration trisubstituted from the two different isonitrile of raw material simple and easy to get
Glyoxaline compound.This reaction meets Atom economy, can efficiently, simply synthesize the imidazoles type with highly functional
Compound.It gets rid of previous synthesis defect: needing often to there is by-product to generate such as acid using highly basic and high temperature.
Develop commercial materials synthesis complicated molecule cheap and easy to get, always is the important research direction of organic chemistry.It is different
Nitrile molecule is participated in organic chemical reactions frequently as a kind of active molecule, for efficiently synthesizing some nitrogen-containing molecules or heterocycle
Compound, the reaction participated in often have many advantages, such as high chemistry, region, stereoselectivity and higher Atom economy
(Chem. Rev., 2015, 115, 2698.).Meanwhile the structure of isonitrile is similar with carbon monoxide, be important the source C1 and
With strong metal coordination ability, transition metal-catalyzed some reactions can be actively engaged in.Up to the present, aryl isonitrile
The reaction that tri-substituted imidazoles are synthesized with isonitrile yet there are no document report.
Summary of the invention
The purpose of the present invention is the isonitrile reaction systems that aryl isonitrile and sulfonyloxy, acyloxy and carbamoyl replace
[3+2] type ring addition reaction of standby trisubstituted azoles method, for example, being existed using two kinds of isonitrile that are simple, being easy to get
It under conditions of mild, directly reacts, one-step synthesis tri-substituted imidazoles, provides a kind of cheap, atom economy
Synthetic method more simply, efficiently synthesizes the glyoxaline compound of highly functional.
The present invention provides a kind of preparation method of the glyoxaline compound of highly functional.In the present invention, we are for the first time
The cycloaddition reaction for having developed a kind of two different isonitrile is prepared for a series of three substituted azoles class compounds.
The glyoxaline compound of synthesis highly functional according to the present invention, reaction equation are as follows:
It reacts to obtain three substitutions in nonaqueous solvents including a kind of aryl isonitrile 1 is heated to 80 DEG C with functional group isonitrile 2
Azoles 3, wherein TG be sulfonyloxy, acyloxy, carbamoyl, R be alkyl, phenyl, ester group, alkenyl, virtue
Base.The tri-substituted imidazoles of high-purity can be efficiently obtained with the method for the present invention.
The preparation method of tri-substituted imidazoles of the invention includes that the cyclization of aryl isonitrile and functional group's isonitrile is anti-
It answers.
Detailed process can be expressed as follows:
(1) in certain reaction temperature and solvent, tri-substituted imidazole class is prepared by aryl isonitrile 1 and functional group's isonitrile 2
Compound 3.
The dosage of functional group's isonitrile 2 is 1.2 times of aryl isonitrile dosage, under nitrogen protection, uses silver carbonate as urging
Agent, reaction temperature are 80 °C.Solvent can choose methylene chloride, Isosorbide-5-Nitrae-dioxane, tetrahydrofuran, dimethyl sulfoxide,
In it is best with 1,4- dioxane.
The present invention have it is easy to operate, raw materials and reagents are easy to get, mild condition, the easily separated purifying of product, be suitable for synthesis
Various polysubstituted glyoxaline compounds can be made three efficiently, in high yield and replace especially suitable for large-scale industrial production
Glyoxaline compound.
Detailed description of the invention
Fig. 1 is imidazoles 3a's1The nuclear magnetic resoance spectrum of H-NMR；
Fig. 2 is imidazoles 3a's13The nuclear magnetic resoance spectrum of C-NMR；
Fig. 3 is imidazoles 3i's1The nuclear magnetic resoance spectrum of H-NMR；
Fig. 4 is imidazoles 3i's13The nuclear magnetic resoance spectrum of C-NMR.
Specific embodiment
The following examples will be helpful to illustrate the present invention, but not limit to its range.
Embodiment 1
The preparation of imdazole derivatives 3a
P-bromophenyl isonitrile 1a(109.2 mg is added into the 10 mL pressure pipes with magnetic stirring apparatus,
0.6mmol, 1.2 equiv), p-toluenesulfonyl isonitrile (103.1 mg, 0.5 mmol, 1.0 equiv) and silver carbonate
(27.6 mg, 10 mol%), stir evenly and are filled with nitrogen protection three times, and Isosorbide-5-Nitrae-dioxane (2 is added by syringe
ML).It is reacted 1 hour in 80 DEG C of oil bath pans, TLC detection substrate disappears, and reaction terminates.It is cooled to room temperature, uses to reaction solution
Mixture is obtained in 35 degrees Celsius of vacuum distillations after silica gel filtering, (eluent is petroleum ether, acetic acid second by silica gel column chromatography
Ester) 161.0 mg of white solid is obtained, imdazole derivatives 3a, yield 82% are turned out to be by NMR, MS.
Spectrum elucidation data 3a:
1H-NMR (500 MHz, CDCl3) δ = 7.48 (d, J = 8.5 Hz, 2H), 7.43 (s, 1H),
7.30 (d, J = 8.5 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 8.5 Hz, 2H),
2.67 (s, 3H), 2.37 (s, 3H); 13C NMR (125 MHz, CDCl3) δ =147.09, 144.42,
140.34, 138.75, 133.84, 131.94, 129.51, 129.45, 127.12, 126.53, 123.93,
21.56, 14.96。
Embodiment 2
The 1e in example 1 is replaced with 1i, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3i:
1H NMR (500 MHz, CDCl3) δ = 8.00 (d, J = 8.5 Hz, 2H), 7.49 (s, 1H),
7.29 (d, J = 8.5 Hz, 2H), 7.15 (dd, J = 13.0, 8.5 Hz, 2H), 4.42 (q, J = 7.0
Hz, 1H), 2.68 (s, 3H), 2.37 (s, 3H), 1.42 (t, J=7.0, 3H); 13C NMR (125 MHz,
CDCl3) δ = 165.24, 147.16, 144.40, 140.19, 138.59, 138.43, 131.57, 129.94,
129.48, 127.75, 126.97, 126.43, 61.46, 21.50, 14.91, 14.21。
Embodiment 3
The 1e in example 1 is replaced with 1j, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3j:
1H NMR (500 MHz, DMSO) δ = 8.29 (d, J = 8.0 Hz, 2H), 8.07 (s, 1H),
7.48 (d, J = 8.5 Hz, 2H), 7.34 (dd, J = 21.1, 7.5 Hz, 4H), 2.54 (s, 3H), 2.36
(s, 3H);13C NMR (125 MHz, DMSO) δ 147.77, 146.53, 144.59, 141.96, 140, 03,
138.30, 130. 01, 129.28, 126.63, 125.49, 123.99, 21.09, 14.66。
Embodiment 4
The 1e in example 1 is replaced with 1q, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3j:
1H NMR (500 MHz, CDCl3) δ = 7.71 (d, J = 8.5 Hz, 2H), 7.64 (d, J =
7.0 Hz,, 1H), 7.53 (td, J = 7.5, 3.5 Hz, 1H), 7.46-7.41 (m, 4H0, 7.24 (dd, J
= 6.5. 0.5 Hz, 1H), 7.17 (d, J = 8.0 Hz, 2H), 6.93 (d, J = 8.5 Hz, 2H), 6.71
(d, J = 16.0 Hz, 1H), 6.64 (d, J = 16.0 Hz, 1H), 2.71 (s, 3H), 2.12 (s, 3H);13C NMR (125 MHz, CDCl3) δ = 189.54, 146.80, 144.47, 140.65, 138.35, 137.34,
133.95, 133.30, 132.96, 130.57, 130.47, 130.26, 129.41, 128.60, 128.37,
127.65, 127.25, 126.86, 124.57, 21.35, 14.97。
Embodiment 5
The methyl isocyanide in example 1 is replaced with benzyl isonitrile, for other conditions with example 1, experimental result is shown in Table 1.
Spectrum elucidation data 3t:
1H NMR (500 MHz, CDCl3) δ = 7.49-7.46 (m, 5H), 7.34 (t, J = 7.5 Hz,
2H), 7.27- 7.24 (m, 2H), 7.08 (dd, J = 8.5 Hz, 4H), 6.93 (d, J = 8.5 Hz, 2H),
4.47 (s, 2H), 2.36 (s, 3H);13C NMR (125 MHz, CDCl3) δ = 149.43, 144.46,
140.83, 139.10, 138.40, 133.67, 131.93, 129.63, 129.43, 129.29, 128.49,
127.32, 126.41, 124.05, 34.34, 21.58。
Embodiment 6
The isonitrile for replacing the tolysulfonyl chloro in example 1 to replace with the isonitrile that acyloxy replaces, other conditions are the same as real
Example 1, experimental result is shown in Table 1.
Spectrum elucidation data 4a:
1H NMR (500 MHz, CDCl3) δ 8.10 (d, J = 8.0 Hz, 2H), 7.88 (d, J = 8.5
Hz, 2H), 7.70 (s,1H), 7.64 (d, J = 8.5 Hz, 2H), 7.25 (d, J = 8.0 Hz, 4H),
4.41 (q, J = 7.0 Hz, 2H), 4.11 (q, J = 7.2 Hz, 2H), 1.42 (t, J = 7.5 Hz,3H),
1.04 (t, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ = 166.51, 159.83, 147.91,
140.61, 137.92, 135.94, 132.34, 130.17, 129.35, 129.07, 127.72, 123.05,
120.67, 61.10, 61.04, 14.37, 13.69。
Embodiment 7
The isonitrile for replacing the p-toluenesulfonyl in example 1 to replace with the isonitrile that carbamoyl replaces, other conditions are same
Example 1, experimental result is shown in Table 1.
Spectrum elucidation data 4e:
1H NMR (500 MHz, CDCl3) δ 7.58-7.55 (m, 3H), 7.31 (d, J = 7.0 Hz,
2H), 7.27 (d, J = 3.0 Hz, 1H), 7.24-7.21 (m, 3H), 7.16 (t, J = 7.0 Hz, 1H),
4.02 (s, 2H), 3.38 (t, J = 7.0 Hz, 2H), 2.67 (t, J = 6.0 Hz, 2H), 1.70 (t, J
= 7.0 Hz, 1H), 1.52 (t, J = 7.0 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ = 161.13,
142.09, 139.44, 135.89, 135.29, 132.92, 128.84, 128.34, 126.18, 124.61,
124.37, 121.84, 47.40, 45.48, 34.21, 25.38, 24.10。
Claims (1)
1. a kind of synthetic method of tri-substituted imidazoles, it is characterized in that its reaction equation is as follows:
Specific steps: p-bromophenyl isonitrile 1a109.2 mg being added into the 10 mL pressure pipes with magnetic stirring apparatus,
0.6mmol, 1.2 equiv, p-toluenesulfonyl isonitrile 103.1 mg, 0.5 mmol, 1.0 equiv and silver carbonate 27.6
Mg, 0.1mmol stir evenly and are filled with nitrogen protection three times, 2 mL of Isosorbide-5-Nitrae-dioxane are added by syringe, at 80 DEG C
Reacted 1 hour in oil bath pan, TLC detection substrate disappears, and reaction terminates, be cooled to room temperature to reaction solution, after being filtered with silica gel
35 degrees Celsius of vacuum distillations obtain mixture, are petroleum ether by eluent, the silica gel column chromatography of ethyl acetate obtains white admittedly
161.0 mg of body, by NMR, obtain MS be imdazole derivatives 3a, yield 82%.
Priority Applications (1)
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| Silver-catalyzed cyclization of 2-pyridyl alkynyl carbinols with isocyanides: divergent synthesis of indolizines and pyrroles;Xianyu Meng et al.,;《Chem. Commun.》;20141231;第50卷;11837-11839 |
| Silver-Catalyzed Isocyanide-Alkyne Cycloaddition: A General and Practical Method to Oligosubstituted Pyrroles;Jianquan Liu et al.,;《Angew. Chem. Int. Ed.》;20130506;第52卷;第6954页Table 1 |
| Synthesis of Imidazoles through the Copper-Catalyzed Cross-Cycloaddition between Two Different Isocyanides;Chikashi Kanazawa et al.,;《J. AM. CHEM. SOC.》;20060727;第128卷(第33期);第10662页左栏反应式1和右栏Table 2 |
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