CN108148021A - 2- imines (3H) furane derivative or thiophene derivant and its synthesis - Google Patents

2- imines (3H) furane derivative or thiophene derivant and its synthesis Download PDF

Info

Publication number
CN108148021A
CN108148021A CN201611102010.1A CN201611102010A CN108148021A CN 108148021 A CN108148021 A CN 108148021A CN 201611102010 A CN201611102010 A CN 201611102010A CN 108148021 A CN108148021 A CN 108148021A
Authority
CN
China
Prior art keywords
methyl
reaction
derivative
alkene
ketone
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.)
Granted
Application number
CN201611102010.1A
Other languages
Chinese (zh)
Other versions
CN108148021B (en
Inventor
黄菲
余正坤
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.)
Dalian Institute of Chemical Physics of CAS
Original Assignee
Dalian Institute of Chemical Physics of CAS
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 Dalian Institute of Chemical Physics of CAS filed Critical Dalian Institute of Chemical Physics of CAS
Priority to CN201611102010.1A priority Critical patent/CN108148021B/en
Publication of CN108148021A publication Critical patent/CN108148021A/en
Application granted granted Critical
Publication of CN108148021B publication Critical patent/CN108148021B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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
    • C07D307/66—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/36—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

The invention discloses a kind of 2 imines (3H) furane derivative (or thiophene) derivative and its synthetic methods.Using 1 alkylthio group, 1 amido, 1 alkene, 3 ketone (or thioketones) and Tosylhydrazone as starting material, mantoquita is catalyst, under alkaline heating condition, pass through cyclisation and Cabbeen intercalation reaction, one step generates 2 imines (3H) furane derivative (or thiophene) derivative, and 2 imines furan derivatives of gained can occur further to be converted into butyrolactone derivative or open loop forms ketone ester structured product.This method raw material is easy to get, is easy to operate, and synthetic reaction condition is mild, reaction efficiency is high, and product stereoselectivity is good, its functional group has diversity.

Description

2- imines (3H) furane derivative or thiophene derivant and its synthesis
Technical field
The present invention relates to a kind of oxygen-containing (or sulphur) heterocyclic compound 2- imines (3H) furane derivatives (or thiophene) of unsaturation Derivative and its synthetic method.It is starting with 1- alkylthio group -1- amido -1- alkene -3- ketone 3 (or thioketones 4) and Tosylhydrazone 5 Raw material, CuBr2For catalyst, in a heated condition, by cyclisation and Cabbeen intercalation reaction, a step generation 2- imines (3H) more take For furans (or thiophene) derivative.
Tosylhydrazone (N-Tosylhydrazone, Angew.Chem.Int.Ed.2011,50,7486-7500； Acc.Chem.Res.2016,49,115-127) it is a kind of very important intermediate in organic synthesis, from the middle of last century quilt It has had been obtained for widely studying and applying since it was found that.Tosylhydrazone can be applied to as a kind of novel coupling component It crosses in the cross-coupling reaction of metal catalytic, efficiently builds carbon-carbon bond, heteroatoms key to synthesize polyfunctional organic compound, Realize synthesis and conversion that other reactions are difficult to realize.
Using Tosylhydrazone as starting material, carbene catalyzed process is undergone, including cyclopropanization reaction, forms ylide Reaction and intercalation reaction etc..For Cabbeen intercalation reaction, what research was more at present is that Cabbeen is inserted into C-H In (Chem.Commun.2015,51,7986-7995) or heteroatomic bond-H (Eur.J.Org.Chem.2016,2369- 2382).And C-C reactions (Chem.Soc.Rev.2016,45,506-516 is inserted into for Cabbeen； J.Am.Chem.Soc.2014,136,3013-3015) research focuses primarily upon the α positions C- of cyclic ketone (or alcohol) class compound Ring expansion occurs for the fracture of C keys, obtains (n+1) first cyclic ketone (or alcohol) class compound.B ü chner classes are reacted (Chem.Ber.1885,18,2371；Angew.Chem.Int.Ed.2015,54,3056-3060；Synlett 2015,26, 59-62) it is phenyl ring under transition-metal catalyst catalysis and diazonium compound, experience metal carbene is inserted into the expansion of phenyl ring carbon-carbon bond Ring reacts, and obtains the reaction of seven-membered compounds, their, there is very extensive application in pharmaceutical synthesis and Material Field.
Alkene C=C is inserted into as metal carbene precursor have no document report by the use of Tosylhydrazone.We use nitrogen sulphur Contracting ketenes, with tolysulfonyl hydrazone reaction, by the use of copper bromide as catalyst, is successfully realized experience card as polarization internal olefin Guest is inserted into alkene C=C, has obtained imines furans product.
Background technology
Imines furans and Furanones compound are widely present in natural products and synthesis compound, have many biologies And pharmaceutical activity, it is widely used in the fields such as medicine, pesticide, fragrance and food.2- imines furan derivatives are in acidity Under the conditions of be easy to hydrolysis generation 2- furanone based derivatives.It is obtained for example, being extracted from natural products gossypol containing imines (GIL, structure is as follows, J.Med.Chem.1991,34,3301-3305 by the gossylic iminolactone of furan structure； Biochem.Pharmacol.2001,62,81-89) there is the activity of AIDS virus resisting.Cyclic lmide Derivatives (ACS Symposium Series 584；American Chemical Society:Washington DC,1995；Chapter 6, Pp 60-69) there is the activity of herbicide.(structure is such as by isolated natural products Spirovibsanin A from sweet viburnum Under) there is many bioactivity (Tetrahedron Lett.2001,42,1081).The polysubstituted 2- furanones of other Derivative such as spiral shell furanone (structure is as follows) have antibacterial and antifungal activity (Bioorg.Med.Chem.2003,11, 407)。
The present invention realizes metal carbene and is inserted into the C=C keys of alkene, synthesizes polysubstituted imines furan derivatives.Hair The Cabbeen of Zhan Xin is inserted into the methodology of organic synthesis of alkenyl C=C keys.And raw material of the present invention is easy to get, is easy to operate, synthetic reaction item Part is mild, efficient, and yield is in 44-82%, and product has good stereoselectivity and functional group's diversity.
Invention content
It is an object of the invention to easily to prepare, have the 1- alkylthio group -1- amidos of structure diversity and more reaction centers - 1- alkene -3- ketone 3 (or thioketones 4) and Tosylhydrazone 5 are raw material, and by intramolecular cyclization and Cabbeen intercalation reaction, a step is real Having showed realizes the generation of C-O keys (or C-S keys) and 2 C-C keys, synthesis with potential drug activity furane derivative (or Thiophene) derivative.
To achieve these goals, technical scheme is as follows：
At 80 DEG C, dithio keteal A is reacted with level-one amine B in alcohol solvent, and generation 1- alkylthio group -1- amido -1- alkene - 3- ketone 3 (reaction equation 1).1- alkylthio group -1- amido -1- alkene -3- ketone 3 obtains 1- alkane sulphur with lawesson reagent under the conditions of refluxing toluene Base -1- amido -1- alkene -3- thioketones 4 (reaction equation 2).Ketone and unifor are prepared pair at 65 DEG C, in methanol solution Tosylhydrazone 5 (reaction equation 3).
Then in argon gas, CuBr2For catalyst, under alkaline condition, in organic solvent, 1- alkylthio group -1- amidos - 1- alkene -3- ketone 3 (or thioketones 4) and Tosylhydrazone 5 are raw material, carry out intramolecular cyclization and Cabbeen intercalation reaction (reaction equation 4,5).Routinely isolation and purification method carries out product separation and characterization after reaction, obtains 2- imines (3H) furane derivative 1 (or thiophene 2) derivative.
Technical solution is characterized in that：
1.1- alkylthio group -1- amido -1- alkene -3- ketone 3 (or thioketones 4) and Tosylhydrazone 5 are reactant, and A and B is 3 Raw material, substituent group is：
R1Selected from following group：Methyl contains different substituents (such as hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, trifluoromethyl Deng) phenyl ring, naphthalene, furyl or thienyl；
R2To be selected from following group：Carbon atom number is alkyl, pi-allyl, benzyl or the heterocycle methylene of 1-18；
R is selected from following group：Methyl, ethyl or benzyl；
R3Selected from following group：Methyl contains different substituents (such as hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, trifluoro Methyl etc.) phenyl ring, naphthalene, furyl or thienyl.
R4Selected from following group：Methyl, ethyl or containing different substituents (such as hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, Iodine, trifluoromethyl etc.) phenyl ring.
2. metallic catalyst is Pd2(dba)3、Pd(OAc)2、Pd(PPh3)2Cl2、RuCl2(PPh3)3、[RuCl2(p- cymene)]2、[Rh(COD)Cl]2、[Cp*RhCl2]2、CuBr、CuI、CuCl2、CuBr2；Wherein, CuI and CuBr2Effect compared with It is good.
3. alkali is one kind in lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, potassium phosphate, potassium tert-butoxide or tert-butyl alcohol lithium； Wherein, tert-butyl alcohol lithium effect is preferable.
4. reaction dissolvent is toluene, 1,4- dioxane, 1,2- dichloroethanes (DCE), dichloromethane (DCM), ethyl alcohol, N, One kind in dinethylformamide (DMF) or dimethyl sulfoxide (DMSO) (DMSO)；Wherein, it reacts and is imitated in aprotic solvent toluene Fruit is best.
5. the molar concentration of raw material 3 (or 4) is 0.05-1.0M, optimal is 0.1M.
6. the reaction time is 0.5-48 hours.Wherein, optimum reacting time is 16-30 hours.
7. reaction temperature is 40-140 DEG C.Wherein, optimal reaction temperature is 100-120 DEG C.
The present invention has the following advantages：
1) raw material 1- alkylthio groups -1- amidos -1- alkene -3- ketone 3 (or thioketones 4) has various structures with Tosylhydrazone 5 Property, it can be used for synthesizing 1 (or thiophene 2) derivative of 2- imines (3H) furane derivative of different type and structure.
2) raw material 3 (or 4) and 5 is easily prepared, and it is cheap and easily-available to prepare raw material, of low cost, is easy to industrialized production.
3) cyclisation of 1 (or thiophene 2) derivative synthetic reaction of 2- imines (3H) furane derivative, one step and Cabbeen are inserted into C=C Key, mild condition, product yield high, can reach 82%.
4) stereoselectivity and functional group that 1 (or thiophene 2) derivative products of 2- imines (3H) furane derivative have had are more Sample, it is with a wide range of applications.
In short, the present invention using 1- alkylthio group -1- amido -1- alkene -3- ketone 3 (or thioketones 4) structure diversity with it is mostly anti- Center is answered to efficiently synthesize 1 (or thiophene 2) derivative of 2- imines (3H) furane derivative of different type and structure, raw material is cheap It is easy to get, the cyclisation of one step of synthetic reaction and Cabbeen are inserted into C=C keys, and easy to operate, target product yield is high, and can be further Function dough.
Specific embodiment
Contribute to further understand the present invention, but present disclosure is not limited to that by following embodiments.
Embodiment 1
In glove box, 1- methyl mercapto -1- benzamido group -1- alkene -3- ketone 3a (0.5mmol), tolysulfonyl are weighed successively Hydrazone 5a (1.5mmol), cuprous iodide (0.1mmol), potassium tert-butoxide (1.5mmol), in 25mL Schlenk reaction bulbs, in nitrogen Under gas, toluene solvant 5mL is added in, is stirred at room temperature 2 minutes, is put into 100 DEG C of oil bath and reacts 12 hours.Reaction terminates Afterwards, mixture being cooled to room temperature, diatomite filtering, ethyl acetate with 10% ammonium hydroxide of mass concentration with extracting, collection organic phase, Anhydrous magnesium sulfate is dried, filtering, depressurize it is lower remove Volatile Colstituent, then detach that (eluent is petroleum ether with silica gel column chromatography (60-90 DEG C)/ethyl acetate, v/v=20:1) colourless liquid target product 1a (128mg, yield 75%), is obtained.Target product It is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measure.
Embodiment 2
In glove box, 1- methyl mercapto -1- benzamido group -1- alkene -3- ketone 3b (0.5mmol), tolysulfonyl are weighed successively Hydrazone 5a (1.5mmol), copper bromide (0.05mmol), tert-butyl alcohol lithium (1.5mmol) is in 25mL Schlenk reaction bulbs, in nitrogen Under, toluene solvant 5mL is added in, is stirred at room temperature 2 minutes, is put into 110 DEG C of oil bath and reacts 24 hours.After reaction, Mixture is cooled to room temperature, diatomite filtering, ethyl acetate collects organic phase, nothing with being extracted with 10% ammonium hydroxide of mass concentration Water magnesium sulfate is dried, filtering, depressurize it is lower remove Volatile Colstituent, then detach that (eluent is petroleum ether (60- with silica gel column chromatography 90 DEG C)/ethyl acetate, v/v=20:1) colourless liquid target product 1b (145mg, yield 82%), is obtained.Target product passes through Nuclear magnetic resoance spectrum and high resolution mass spectrum measure are confirmed.
Embodiment 3
In glove box, 1- methyl mercapto -1- benzamido group -1- alkene -3- ketone 3d (0.5mmol), tolysulfonyl are weighed successively Hydrazone 5a (0.5mmol), Pd2(dba)3(0.025mmol), lithium carbonate (0.5mmol) is in 25mL Schlenk reaction bulbs, in argon Under gas, Isosorbide-5-Nitrae-dioxane solvent 5mL are added in, is stirred at room temperature 2 minutes, is put into 100 DEG C of oil bath and reacts 48 hours.Instead After answering, mixture is cooled to room temperature, diatomite filtering, ethyl acetate is collected with being extracted with 10% ammonium hydroxide of mass concentration Organic phase, anhydrous magnesium sulfate drying, filtering, depressurize it is lower remove Volatile Colstituent, then detach that (eluent is stone with silica gel column chromatography Oily ether (60-90 DEG C)/ethyl acetate, v/v=20:1) colourless liquid target product 1d (129mg, yield 69%), is obtained.Target Product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measure.
Embodiment 4
In glove box, 1- methyl mercapto -1- benzamido group -1- alkene -3- ketone 3e (0.5mmol), tolysulfonyl are weighed successively Hydrazone 5a (2.0mmol), RuCl2(PPh3)3(0.15mmol), tert-butyl alcohol lithium (1.5mmol) in 25mL Schlenk reaction bulbs, Under a nitrogen, alcohol solvent 10mL is added in, is stirred at room temperature 2 minutes, is put into 80 DEG C of oil bath and reacts 40 hours.Reaction knot Mixture is cooled to room temperature by Shu Hou, diatomite filtering, and ethyl acetate is collected organic with being extracted with 10% ammonium hydroxide of mass concentration Phase, anhydrous magnesium sulfate drying, filtering, depressurize it is lower remove Volatile Colstituent, then detach that (eluent is petroleum ether with silica gel column chromatography (60-90 DEG C)/ethyl acetate, v/v=20:1) colourless liquid target product 1e (109mg, yield 66%), is obtained.Target product It is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measure.
Embodiment 5
In glove box, 1- methyl mercapto -1- methylamino -1- alkene -3- ketone 3g (0.5mmol), tolysulfonyl are weighed successively Hydrazone 5a (1.5mmol), cuprous iodide (0.05mmol), potassium tert-butoxide (1.5mmol) is in 25mL Schlenk reaction bulbs, in nitrogen Under gas, DCM solvent 20mL are added in, is stirred at room temperature 2 minutes, is put into 40 DEG C of oil bath and reacts 16 hours.After reaction, Mixture is cooled to room temperature, diatomite filtering, ethyl acetate collects organic phase, nothing with being extracted with 10% ammonium hydroxide of mass concentration Water magnesium sulfate is dried, filtering, depressurize it is lower remove Volatile Colstituent, then detach that (eluent is petroleum ether (60- with silica gel column chromatography 90 DEG C)/ethyl acetate, v/v=20:1) colourless liquid target product 1g (100mg, yield 76%), is obtained.Target product passes through Nuclear magnetic resoance spectrum and high resolution mass spectrum measure are confirmed.
Embodiment 6
In glove box, 1- methyl mercapto -1- octadecylamine base -1- alkene -3- ketone 3h (0.5mmol) are weighed successively, to toluene sulphur Acylhydrazone 5a (2.0mmol), cuprous bromide (0.1mmol), tert-butyl alcohol lithium (2.0mmol) in 25mL Schlenk reaction bulbs, Under nitrogen, toluene solvant 5mL is added in, is stirred at room temperature 2 minutes, is put into 60 DEG C of oil bath and reacts 6 hours.Reaction terminates Afterwards, mixture being cooled to room temperature, diatomite filtering, ethyl acetate with 10% ammonium hydroxide of mass concentration with extracting, collection organic phase, Anhydrous magnesium sulfate is dried, filtering, depressurize it is lower remove Volatile Colstituent, then detach that (eluent is petroleum ether with silica gel column chromatography (60-90 DEG C)/ethyl acetate, v/v=20:1) colourless liquid target product 1h (148mg, yield 59%), is obtained.Target product It is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measure.
Embodiment 7
In glove box, 1- methyl mercapto -1- furans methylene amido -1- alkene -3- ketone 3j (0.5mmol) are weighed successively, to first Benzene sulfonyl hydrazone 5a (1.5mmol), cuprous iodide (0.1mmol), potassium tert-butoxide (1.5mmol) is in 25mL Schlenk reaction bulbs In, under a nitrogen, alcohol solvent 5mL is added in, is stirred at room temperature 2 minutes, is put into 70 DEG C of oil bath and reacts 48 hours.Reaction After, mixture is cooled to room temperature, diatomite filtering, with being extracted with 10% ammonium hydroxide of mass concentration, collection has ethyl acetate Machine phase, anhydrous magnesium sulfate drying, filtering, depressurize it is lower remove Volatile Colstituent, then detach that (eluent is oil with silica gel column chromatography Ether (60-90 DEG C)/ethyl acetate, v/v=20:1) colourless liquid target product 1j (130mg, yield 79%), is obtained.Target is produced Object is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measure.
Embodiment 8
In glove box, 1- methyl mercapto -1- benzamido group -1- alkene -3- ketone 3a (0.5mmol), tolysulfonyl are weighed successively Hydrazone 5c (1.5mmol), cuprous iodide (0.1mmol), potassium phosphate (1.5mmol) is in 25mL Schlenk reaction bulbs, in nitrogen Under, solvent DMF 5mL is added in, is stirred at room temperature 2 minutes, is put into 100 DEG C of oil bath and reacts 2 hours.After reaction, will Mixture is cooled to room temperature, diatomite filtering, and ethyl acetate with 10% ammonium hydroxide of mass concentration with extracting, and collection organic phase is anhydrous Magnesium sulfate is dried, filtering, depressurize it is lower remove Volatile Colstituent, then detach that (eluent is petroleum ether (60-90 with silica gel column chromatography DEG C)/ethyl acetate, v/v=20:1) colourless liquid target product 1l (118mg, yield 68%), is obtained.Target product passes through core Magnetic resonance spectrum and high resolution mass spectrum measure are confirmed.
Embodiment 9
In glove box, 1- methyl mercapto -1- benzamido group -1- alkene -3- thioketones 4a (0.5mmol) are weighed successively, to toluene sulphur Acylhydrazone 5a (1.5mmol), cuprous iodide (0.05mmol), potassium tert-butoxide (1.5mmol) in 25mL Schlenk reaction bulbs, Under nitrogen, solvent toluene 5mL is added in, is stirred at room temperature 2 minutes, is put into 100 DEG C of oil bath and reacts 12 hours.Reaction terminates Afterwards, mixture being cooled to room temperature, diatomite filtering, ethyl acetate with 10% ammonium hydroxide of mass concentration with extracting, collection organic phase, Anhydrous magnesium sulfate is dried, filtering, depressurize it is lower remove Volatile Colstituent, then detach that (eluent is petroleum ether with silica gel column chromatography (60-90 DEG C)/ethyl acetate, v/v=20:1) colourless liquid target product 2a (119mg, yield 67%), is obtained.Target product It is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measure.

Claims (6)

1. a kind of 2- imines (3H) furane derivative or thiophene derivant, 2- imines (3H) furane derivative derivative 1 or 2- are sub- Amine (3H) polysubstituted thiophene derivative 2, molecular structural formula is as follows：
R1Selected from following group：Methyl, containing different substituents (in such as hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, trifluoromethyl One or two or more kinds) phenyl ring, naphthalene, furyl or thienyl；
R2To be selected from following group：Carbon atom number is alkyl, pi-allyl, benzyl, fural or the tetrahydrofuran methylene of 1-18 Base；
R3Selected from following group：Methyl contains different substituents (such as hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, trifluoromethyl In one or two or more kinds) phenyl ring, naphthalene, furyl or thienyl；
R4Selected from following group：Methyl, ethyl contain different substituents (such as hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, trifluoro One or two or more kinds in methyl etc.) phenyl ring.
2. the synthetic method of 2- imines (3H) furane derivative (or thiophene) derivative, feature exist described in a kind of claim 1 In：With 1- alkylthio group -1- amido -1- alkene -3- ketone 3 (or thioketones 4) and Tosylhydrazone 5 for starting material, transition metal is Under alkaline heating condition, cyclisation and Cabbeen intercalation reaction occur for catalyst in solvent, step generation 2- imines (3H) is polysubstituted Furan derivatives 1 or 2- imines (3H) polysubstituted thiophene derivative 2；
The molecular structural formula of 1- alkylthio group -1- amido -1- alkene -3- ketone 3 (or thioketones 4) and Tosylhydrazone 5 is as follows,
R1Selected from following group：Methyl, containing in different substituents (such as hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, trifluoromethyl) One or two or more kinds of phenyl ring, naphthalene, furyl or thienyls；
R2To be selected from following group：Carbon atom number is alkyl, pi-allyl, benzyl or the heterocycle methylene of 1-18；
R is selected from following group：Methyl, ethyl or benzyl；
R3Selected from following group：Methyl contains different substituents (such as hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, trifluoromethyl In one or two or more kinds) phenyl ring, naphthalene, furyl or thienyl；
R4Selected from following group：Methyl, ethyl contain different substituents (such as hydrogen, methyl, methoxyl group, fluorine, chlorine, bromine, iodine, trifluoro One or two or more kinds in methyl etc.) phenyl ring；
Synthetic route as shown in following reaction equations,
3. synthetic method described in accordance with the claim 2, it is characterised in that：
Wherein：The molar ratio of 1- alkylthio group -1- amido -1- alkene -3- ketone 3 (or thioketones 4) and Tosylhydrazone 5 is 1:1-1:4；
Metallic catalyst is Pd2(dba)3、Pd(OAc)2、Pd(PPh3)2Cl2、RuCl2(PPh3)3、[RuCl2(p-cymene)]2、 [Rh(COD)Cl]2、[Cp*RhCl2]2、CuBr、CuI、CuCl2、CuBr2In one or two or more kinds, 1- alkylthio group -1- amine The molar ratio of base -1- alkene -3- ketone 3 (or thioketones 4) and metallic catalyst is 1:0.05-1:0.3；
Alkali is lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, potassium phosphate, potassium tert-butoxide or one kind in tert-butyl alcohol lithium or two kinds with On, the molar ratio of 3 (or 4) and alkali is 1:1-1:4；
Reaction dissolvent is toluene, 1,4- dioxane, 1,2- dichloroethanes (DCE), dichloromethane (DCM), ethyl alcohol, N, N- diformazans One or two or more kinds in base formamide (DMF) or dimethyl sulfoxide (DMSO) (DMSO)；1- alkylthio group -1- amido -1- alkene -3- ketone 3 The molar concentration of (or thioketones 4) in reaction dissolvent is 0.05-1.0M；
Reaction atmosphere is nitrogen and/or argon gas；Reaction time is 0.5-48 hours；Reaction temperature is 40-140 DEG C.
4. according to the synthetic method described in Claims 2 or 3, it is characterised in that：1- alkylthio group -1- amido -1- alkene -3- ketone 3 (or Thioketones 4) 1 (or 2) of generation reaction in the preferred molar ratio of 3 (or 4) and metallic catalyst be 1:0.2.
5. according to the synthetic method described in Claims 2 or 3, it is characterised in that：1- alkylthio group -1- amido -1- alkene -3- ketone 3 (or Thioketones 4) 1 (or 2) of generation reaction in the preferred molar ratio of 3 (or 4) and alkali be 1:3.
6. according to the synthetic method described in Claims 2 or 3, it is characterised in that：1- alkylthio group -1- amido -1- alkene -3- ketone 3 (or Thioketones 4) generation 1 (or 2) reaction carried out preferably in aprotic solvent.
CN201611102010.1A 2016-12-05 2016-12-05 2-imine (3H) polysubstituted furan or thiophene derivative and synthesis thereof Active CN108148021B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201611102010.1A CN108148021B (en) 2016-12-05 2016-12-05 2-imine (3H) polysubstituted furan or thiophene derivative and synthesis thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201611102010.1A CN108148021B (en) 2016-12-05 2016-12-05 2-imine (3H) polysubstituted furan or thiophene derivative and synthesis thereof

Publications (2)

Publication Number Publication Date
CN108148021A true CN108148021A (en) 2018-06-12
CN108148021B CN108148021B (en) 2021-04-20

Family

ID=62470858

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201611102010.1A Active CN108148021B (en) 2016-12-05 2016-12-05 2-imine (3H) polysubstituted furan or thiophene derivative and synthesis thereof

Country Status (1)

Country Link
CN (1) CN108148021B (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111269210A (en) * 2018-12-05 2020-06-12 中国科学院大连化学物理研究所 Cyanoalkyl substituted thiophene derivative and synthesis thereof
CN113549049A (en) * 2020-04-23 2021-10-26 中国科学院大连化学物理研究所 Polysubstituted thienocyclopentanone derivative and synthetic method thereof
CN115477627A (en) * 2022-05-23 2022-12-16 南京工业大学 Polysubstituted 2-furanone compound and synthesis method thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101508688A (en) * 2009-03-24 2009-08-19 浙江大学 Synthesis method for Z-difuryl imine compounds

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101508688A (en) * 2009-03-24 2009-08-19 浙江大学 Synthesis method for Z-difuryl imine compounds

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
AHMAD SHAABANI等: "[1+4] Cycloaddition of Isocyanides with 3-(1-Hydroxyethylidene)pentane-2,4-dione. A Convenient Synthesis of Iminolactones", 《J. CHEM. RESEARCH》 *
FEI HUANG等: "Copper-Catalyzed Formal Carbene Migratory Insertion into Internal Olefinic C=C Bonds with N-Tosylhydrazones To Access Iminofuran and 2(3H)-Furanone Derivatives", 《ORG. LETT.》 *
MASAYUKI OSHITA等: "Catalytic [4+1] Cycloaddition of α,β-Unsaturated Carbonyl Compounds with Isocyanides", 《J. AM. CHEM. SOC.》 *
NAOTO CHATANI等: "A GaCl3-Catalyzed [4+1] Cycloaddition of α,β-Unsaturated Carbonyl Compounds and Isocyanides Leading to Unsaturated γ-Lactone Derivatives", 《J. AM. CHEM. SOC.》 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111269210A (en) * 2018-12-05 2020-06-12 中国科学院大连化学物理研究所 Cyanoalkyl substituted thiophene derivative and synthesis thereof
CN111269210B (en) * 2018-12-05 2021-02-12 中国科学院大连化学物理研究所 Cyanoalkyl substituted thiophene derivative and synthesis thereof
CN113549049A (en) * 2020-04-23 2021-10-26 中国科学院大连化学物理研究所 Polysubstituted thienocyclopentanone derivative and synthetic method thereof
CN113549049B (en) * 2020-04-23 2022-04-15 中国科学院大连化学物理研究所 Polysubstituted thienocyclopentanone derivative and synthetic method thereof
CN115477627A (en) * 2022-05-23 2022-12-16 南京工业大学 Polysubstituted 2-furanone compound and synthesis method thereof
CN115477627B (en) * 2022-05-23 2023-12-22 南京工业大学 Polysubstituted 2-furanone compound and synthesis method thereof

Also Published As

Publication number Publication date
CN108148021B (en) 2021-04-20

Similar Documents

Publication Publication Date Title
Murthy et al. Facile and efficient synthesis of 3, 4, 5-substituted furan-2 (5H)-ones by using β-cyclodextrin as reusable catalyst
Adib et al. Synthesis of 2-(alkylamino)-5-{alkyl [(2-oxo-2H-chromen-3-yl) carbonyl] amino}-3, 4-furandicarboxylates using a multi-component reaction in water
Liu et al. Facile one-pot three-component reaction to synthesize trifluoromethylated cyclopenta [b] pyran derivatives and their further transformation
Devalankar et al. Organocatalytic sequential α-aminoxylation and cis-Wittig olefination of aldehydes: synthesis of enantiopure γ-butenolides
Bhat et al. A catalyst-and solvent-free three-component reaction for the regioselective one-pot access to polyfunctionalized pyrroles
CN108148021A (en) 2- imines (3H) furane derivative or thiophene derivant and its synthesis
CN106349147A (en) Synthetic method of pyrrole derivatives
CN103694204B (en) 1,2,4-trisubstituent furan compound and preparation method thereof
He et al. Enantioselective syntheses of 3, 4, 5-trisubstituted γ-lactones: formal synthesis of (−)-blastmycinolactol
Braukmüller et al. Enantioselective butenolide preparation for straightforward asymmetric syntheses of γ‐lactones–paraconic acids, avenaciolide, and hydroxylated eleutherol
Cherry et al. Regioselective synthesis of 5-alkylidene and 5-(iodoalkylidene)-pyrrol-2 (5H)-ones by halolactamisation of (2Z, 4E)-dienamides and (Z)-alk-2-en-4-ynamides
CN110183317B (en) Method for generating cyclopentenones through furfuryl alcohol cyclization conversion
CN108314642B (en) Synthetic method of 2-methylpyridine compound
CN113121516A (en) Compound and method for preparing compound by catalyzing 5-chloromethyl furfural with carbene
Sun et al. Iron‐Catalyzed [4C+ 1N] Cyclization of 4‐Acetylenic Ketones with Primary Amines: Synthesis of 5‐(Aryl) alkylidene‐4, 5‐dihydropyrroles
Terzidis et al. Chromeno [2, 3-c] pyrroles by one-pot multicomponent domino addition–amination reaction
Zhu et al. Palladium (0)-catalyzed cyclization of 1, 6-diyn-3-yl carbonates with a nucleophilic functionality: efficient synthesis of polycyclic benzo [b] fluorene derivatives via allene intermediates
CN115197232A (en) Cyclopropane fused oxygen bridge hexacyclic compound and synthesis method thereof
CN106748964B (en) 2- alkane sulphur (oxygen) base -3- azabicyclic [3,1,0] -2- cyclohexene derivative and its synthesis
Velazquez et al. Efficient and straightforward preparation of a building block for (−)-teubrevin G synthesis via chemically diversed oriented synthesis
Sandaroos et al. Multicomponent synthesis of a new series of 4 H-furo [3, 4-b] pyrans, with iron (III) triflate as catalyst
Boshta et al. Synthesis of 2, 2-functionalized benzo [1, 3] dioxoles
CN108285415B (en) Preparation method of 1, 5-diketone compound
CN106866496B (en) Hexahydro benzoquinoline -6- ketone and hexahydro benzindole -5- ketone compound, synthetic method and purposes
CN108299198B (en) Preparation method of 1, 4-diketone compound

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
GR01 Patent grant
GR01 Patent grant