CN106866541A - A kind of method for preparing benzimidazoles derivative - Google Patents
A kind of method for preparing benzimidazoles derivative Download PDFInfo
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- CN106866541A CN106866541A CN201510920905.5A CN201510920905A CN106866541A CN 106866541 A CN106866541 A CN 106866541A CN 201510920905 A CN201510920905 A CN 201510920905A CN 106866541 A CN106866541 A CN 106866541A
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- aryl
- method described
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- nitrone
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
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- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The present invention relates to a kind of method for preparing benzimidazoles derivative.Benzimidazoles derivative prepared and itself cycloaddition reaction under the cobaltic catalytic condition of transition metal by nitrone compound in specific method there is.Reactant nitrone can be prepared by initiation material cheap and easy to get in the method, and operation is simple, mild condition, wide application range of substrates.
Description
Technical field
The present invention relates to a kind of method for preparing benzimidazoles derivative.Specific method is by being simply prepared into
To nitrone transition metal trivalent cobalt catalysis under cycloaddition reaction prepare benzimidazoles derivative.
Background technology
Benzimidazole and its derivative are one of important heterocyclic compounds, and such compound is widely present in many
In natural products and medicine, with very important bioactivity and pharmaceutical activity.(document 1：a)Alamgir,
M.；Black,D.S.C.；Kumar,N.Top.Heterocycl.Chem.2007,9,87；b)
Bansal,Y.；Silakari,O.Bioorg.Med.Chem.2012,20,6208；c)Narasimhan,
B.；Sharma,D.；Kumar,P.Med.Chem.Res.2012,21,269；d)Shah,K.；
Chhabra,S.；Shrivastava,S.K.；Mishra,P.Med.Chem.Res.2013,22,
5077.) synthesizing benzimidazole analog derivative mainly has two categories below method at present：Method one：By 1,2- bis-
Amino benzene-like compounds prepare (document 2 with carboxylic acid by condensation reaction dehydration：a)Preston,P.N.In
The Chemistry of Heterocyclic Compounds；Weissberger,A.,Taylor,E.C.,
Eds.；John Wiley&Sons:New York,1981；Vol.40:Benzimidazoles and
Cogeneric Tricyclic Compounds p 6.b)Lin,S.-Y.；Isome,Y.；Stewart,
E.；Liu,J.-F.；Yohannes,D.；Yu,L.Tetrahedron Lett.2006,47,2883)；
Method two：There is cross-coupling reaction with aldehyde under metal catalyzed conditions and obtain in 1,2- diaminourea benzene-like compounds
Benzimidazoles derivative.(document 3：a)Chari,M.A.；Shobha,D.；Sasaki,T.
Tetrahedron Lett.2011,52,5575.b)Bahrami,K.；Khodaei,M.M.；Naali,
F.Synlett.2009,569.c)Sharghi,H.；Aberi,M.；Doroodmand,M.M.Adv.
Synth.Catal.2008,350,2380.).This patent be then by being catalyzed in metallic cobalt under, nitrone from
There is cycloaddition reaction to prepare benzimidazoles derivative in body, the strong activation of C-H is related in reaction.The method
Raw material is cheap and easy to get, easy to operate, mild condition.
The content of the invention
The present invention relates to a kind of method for preparing benzimidazoles derivative.
By nitrone benzimidazoles derivative is prepared under the catalysis of trivalent cobalt
A kind of synthesis step of the benzimidazoles derivative of reaction equation 1.
Concrete operation step is as follows：
Reacted in reactor, reactor leads to argon gas after vacuumizing replaces three times.Before adding cobalt salt metal
Body [Cp*Co (CO) I2] (0.025 mM, 10.5 milligrams) and silver salt silver hexafluoroantimonate (0.05 mM,
17.2 milligrams), 2 milliliters of solvents are added after argon gas displacement, after stirring 10 minutes at room temperature, substrate 1 (0.5
MM) be heated to 120 DEG C react 12 hours.Then solvent, column chromatography for separation are transferred with Rotary Evaporators
Obtain pure products.
The invention has the advantages that：
1. reactant nitrone is obtained by raw material aldehyde cheap and easy to get, nitrobenzene through simple reaction step
2. the reaction of the benzimidazoles derivative 2 of generation only needs a kind of reactant and simple to operate, reaction
Mild condition.
Brief description of the drawings
Fig. 1 is one of product spectrogram of embodiment 1；
Fig. 2 is the two of the product spectrogram of embodiment 1；
Fig. 3 is one of product spectrogram of embodiment 2；
Fig. 4 is the two of the product spectrogram of embodiment 2.
Specific embodiment
Embodiment 1
Reacted in 10ml Schlenk reaction tubes, reaction tube vacuumize after lead to argon gas replace three times after,
Add Cp*Co (CO) I of 5mol% (0.025mmol, 11.9mg)2, 10mol%AgSbF6(0.05
Mmol, 17.2mg) and 2ml solvent 1,2- dichloroethanes, stir 10min；It is subsequently adding 0.5mmol
The nitrone 1a of (98.6mg) is heated to 120 DEG C and reacts 12 hours.After reaction terminates, Rotary Evaporators are used
After taking out solvent, solid is dissolved in dichloromethane loading carries out silica gel column chromatography, uses petroleum ether：Ethyl acetate=
10:The eluant, eluent of 1 (volume ratio) rinses pillar, obtains the white solid benzimidizole derivatives of 57.4mg
2a, separation yield is 81%.
The characterize data of 2a is as follows：
1H NMR (400MHz, Acetone) δ 7.64 (d, J=7.8Hz, 1H), 7.48-7.40
(m,4H),7.33–7.02(m,9H)；(spectrogram is shown in Figure of description 1)
13C NMR(101MHz,Acetone)δ152.1,143.2,137.2,130.4,123.0,129.4,
129.3,128.7,128.2,127.6,123.2,122.7,119.6,110.4. (spectrogram is shown in explanation
Book accompanying drawing 2)
Embodiment 2
Reacted in 10ml Schlenk reaction tubes, reaction tube vacuumize after lead to argon gas replace three times after,
Add Cp*Co (CO) I of 5mol% (0.025mmol, 11.9mg)2, 10mol%AgSbF6(0.05
Mmol, 17.2mg) and 2ml solvent 1,2- dichloroethanes, stir 10min；It is subsequently adding 0.5mmol
The nitrone 1b of (120.7mg) is heated to 120 DEG C and reacts 12 hours.After reaction terminates, rotary evaporation is used
After instrument takes out solvent, solid is dissolved in dichloromethane loading carries out silica gel column chromatography, uses petroleum ether：Ethyl acetate=
10:The eluant, eluent of 1 (volume ratio) rinses pillar, obtains the yellow oily benzimidizole derivatives of 62.4mg
2b, separation yield is 78%.
The sign number of 2b is as follows：
1H NMR(400MHz,CDCl3)δ7.77–7.63(m,4H),7.38–7.26(m,6H),
7.24–7.15(m,3H),6.33(s,1H),4.39(s,2H),4.21(s,2H),2.92(s,
2H),2.42(s,3H),2.18(s,3H)；(spectrogram is shown in Figure of description 3)
13C NMR(100MHz,CDCl3)δ160.4,152.0,140.9,138.5,137.5,134.6,
133.0,130.8,130.5,128.9,127.3,124.3,122.5,118.9,113.7,110.2,
55.3,21.8,21.3. (spectrogram is shown in Figure of description 4).
Claims (7)
1. a kind of method for preparing benzimidazoles derivative,
With shown in following formula by nitrone (1) for raw material synthesizes benzo in the case where silver salt and transition metal trivalent cobalt are catalyzed
Imdazole derivatives (2), reaction equation is as follows：
Wherein Ar1It is heteroaryl perfume base or aryl containing hetero atom O or S, aryl is phenyl, naphthyl or phenyl ring
The aryl of the substituted base of upper band；R1It is C1-C10 alkyl, heteroaryl perfume base or aryl containing hetero atom O or S,
Aryl is the aryl of phenyl, naphthyl or the substituted base of phenyl ring upper band.
2. in accordance with the method for claim 1, it is characterised in that：
Concrete operation step is as follows：
Reactor leads to argon gas displacement after vacuumizing, add catalyst cobalt salt, silver salt and solvent, is subsequently adding nitre
Ketone 1,12h-24h is reacted at last 50 DEG C -120 DEG C；After reaction terminates, solvent is taken out with Rotary Evaporators,
Solid is dissolved in dichloromethane loading carries out silica gel column chromatography, obtains benzimidazoles derivative 2.
3. according to the method described in claim 1 or 2, it is characterised in that：
Heteroaryl perfume base containing hetero atom O or S is thienyl or furyl.
4. according to the method described in claim 1 or 2, it is characterised in that：Cobalt salts are [Cp*Co (CO) I2]
Or [Cp*Co (CO) Cl2], silver salt is silver hexafluoroantimonate or silver trifluoromethanesulfonate；The catalyst cobalt salt that is added and
The amount of silver salt is respectively 0.05 with the mol ratio of nitrone:1-0.1:1.
5. according to the method described in claim 1 or 2, it is characterised in that：Solvent 1,2- dichloroethanes,
One kind or two in dichloromethane, toluene, tetrahydrofuran, 1,4- dioxane and N,N-dimethylformamide
More than kind.
6. according to the method described in claim 1 or 2, it is characterised in that：Range of reaction temperature is at 50 DEG C
-120℃；Reaction time is 12h-24h.
7. according to the method described in claim 1 or 2, it is characterised in that：The consumption of solvent is 10
Ml/mmol nitrones (1) -20ml/mmol nitrones (1).
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1847231A (en) * | 2005-04-15 | 2006-10-18 | 沈阳化工研究院 | Process of preparing aromatic ring substituted ixooxazoline compound |
| CN102408376A (en) * | 2011-10-21 | 2012-04-11 | 浙江工业大学 | Synthesis method of tetra-substituted iminazole |
| CN105061304A (en) * | 2015-06-05 | 2015-11-18 | 沈阳科创化学品有限公司 | Method for preparing isoxazoline compound and intermediate thereof |
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2015
- 2015-12-11 CN CN201510920905.5A patent/CN106866541B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1847231A (en) * | 2005-04-15 | 2006-10-18 | 沈阳化工研究院 | Process of preparing aromatic ring substituted ixooxazoline compound |
| CN102408376A (en) * | 2011-10-21 | 2012-04-11 | 浙江工业大学 | Synthesis method of tetra-substituted iminazole |
| CN105061304A (en) * | 2015-06-05 | 2015-11-18 | 沈阳科创化学品有限公司 | Method for preparing isoxazoline compound and intermediate thereof |
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Granted publication date: 20190301 Termination date: 20211211 |