CN103214394A - Alkynyl imine derivative - Google Patents
Alkynyl imine derivative Download PDFInfo
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- CN103214394A CN103214394A CN2013101488639A CN201310148863A CN103214394A CN 103214394 A CN103214394 A CN 103214394A CN 2013101488639 A CN2013101488639 A CN 2013101488639A CN 201310148863 A CN201310148863 A CN 201310148863A CN 103214394 A CN103214394 A CN 103214394A
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- SWWINRJSAAIFBL-WJTDDFOZSA-N CCCCC#C/C(/c1ccccc1N(C(CC)=C)c1ccccc1)=N\C Chemical compound CCCCC#C/C(/c1ccccc1N(C(CC)=C)c1ccccc1)=N\C SWWINRJSAAIFBL-WJTDDFOZSA-N 0.000 description 1
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Abstract
The invention provides an alkynyl imine derivative and a synthesis method thereof. According to the method, the 1-o-amino aryl substituted alkynyl imine derivative is prepared from carbodiimide, terminal alkyne, benzyne precursors and activated fluorine ions, the yield is high, and the synthesis method is scientific and reasonable, so that the universal method for synthesizing the alkynyl imine derivative with multiple substituent groups is provided. The method has the advantages of easily-obtained raw materials, wide application range and high separation yield; and experimental equipment and operation are simple and feasible, and further development and application are facilitated.
Description
Technical field
The present invention relates to a kind of alkynyl imine derivative, relate in particular to alkynyl imine derivative and synthetic method thereof that 1 adjacent amido aryl replaces.
Background technology
Having in the multiple substituent alkynyl imine derivative molecule and have alkynyl imines fragment, is synthon important in the organic synthesis, and can guidance quality synthetic a series of nitrogen-containing heterocycle compounds also have important use at medicine aspect the synthetic and investigation of materials.
As described below, reported the application of 1-alkynyl group with imine moiety in synthetic.
" A Multicomponent Reaction of Arynes; Isocyanides; and Terminal Alkynes:Highly Chemo-and Regioselective Synthesis of Polysubstituted Pyridines and Isoquinolines.Angew.Chem.Int.Ed.2009; 48; 3458 " put down in writing the alkynyl imines can with alkyne reaction pyridine synthesis derivative, with the synthetic isoquinilone derivatives of benzyne reaction." A Novel Cu-Assisted Cycloisomerization of Alkynyl Imines:Efficient Synthesis of Pyrroles and Pyrrole-Containing Heterocycles.J.Am.Chem.Soc.2001; 123; 2074 ", " Metal-Catalyzed 1; 2-Shift of Diverse Migrating Groups in Allenyl Systems as a New Paradigm toward Densely Functionalized Heterocycles.J.Am.Chem.Soc.2008; 130,1440 " has all been put down in writing the alkynyl imines and has been become cycloisomerisation to generate pyrrole derivative under metal catalytic." Innovative Synthesis of4-Carbaldehydepyrrolin-2-ones by Zwitterionic Rhodium Catalyzed Chemo-and Regioselective Tandem Cyclohydrocarbonylation/CO Insertion of α-Imino Alkynes.J.Am.Chem.Soc.2001; 123,10214 " put down in writing rhodium catalysis alkynyl imines and inserted H
2/ CO
2The derivative of synthetic pyrrolinone." Stereodivergent Synthesis of β-Lactams Using Thermal Rearrangement of Aminocyclobutenones.Org.Lett.; 2009; 11,3266 " put down in writing Louis acid catalysis alkynyl imines and the reaction of thiazolinyl silicon ether generates cyclobutene ketone and azetinone." Chemodivergent Transformations of Alkynyl Imines.Synlett 2006,14,2325 " put down in writing the isomerization reaction of monovalence copper catalysis alkynyl imines and generated the condensed ring pyrroline.
The synthetic method of the alkynyl imine derivative that present domestic and foreign literature provides all has its limitation.Raw material is not easy to obtain, and needs catalyzer, and reaction conditions is violent, and productive rate is lower, and regioselectivity is relatively poor, and functional group's tolerance is relatively poor, and substituent kind is restricted.
Summary of the invention
The invention provides a kind of alkynyl imine derivative, especially 1 substituted alkynyl imine derivative.More specifically, provide a kind of 1 quilt alkynyl imine derivative that adjacent amido aryl replaces.
The present invention also provides a kind of synthetic method of alkynyl imine derivative of 1 replacement, especially the synthetic method of the alkynyl imine derivative of the adjacent amido aryl replacement of 1-.The alkynyl imines that this synthetic method replaces from the adjacent amido aryl of the synthetic 1-of the general industrial chemicals that cheaply is easy to get, the efficient height, cost is low, compares with existent method, has bigger advantage.
Technical scheme of the present invention is as follows:
The compound of a kind of general formula (1) expression,
In the formula,
Ar is an aromatic nucleus, represents monocycle, encircles and heterocycle more,
R
1, R
2, R
3Identical or different with R, represent that functional groups such as hydrogen atom, halogen, pseudohalogen, nitro, trifluoromethyl, carbonyl, ester group, amide group replace or the C of non-replacement
1-12The C of alkyl, replacement or non-replacement
1-12The C of alkoxyl group, replacement or non-replacement
2-12The C of alkoxy carbonyl, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical.
R
1, R
2Identical or different, derive from carbodiimide both sides substituting group, respectively the C of expression replacement or non-replacement
1-12The C of alkyl, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical,
R
3Derive from the Terminal Acetylenes substituting group, be the C of replacement of functional groups such as hydrogen atom, halogen, pseudohalogen, nitro, trifluoromethyl, carbonyl, ester group, amide group or non-replacement
1-12The C of alkyl, replacement or non-replacement
1-12The C of alkoxyl group, replacement or non-replacement
2-12The C of alkoxy carbonyl, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical,
R is positioned on the aromatic nucleus, derives from the substituting group of aryne precursor, represents that functional groups such as hydrogen atom, halogen, pseudohalogen, nitro, trifluoromethyl, carbonyl, ester group, amide group replace or the C of non-replacement
1-12The C of alkyl, replacement or non-replacement
1-12The C of alkoxyl group, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical.
The compounds of this invention preferably has the structure shown in the formula (IV):
Wherein,
R
1, R
2Identical or different, expression replaces or the C of non-replacement respectively
1-12The C of alkyl, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical,
R
3Represent that functional groups such as hydrogen atom, halogen, pseudohalogen, nitro, trifluoromethyl, carbonyl, ester group, amide group replace or the C of non-replacement
1-12The C of alkyl, replacement or non-replacement
1-12The C of alkoxyl group, replacement or non-replacement
2-12The C of alkoxy carbonyl, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical,
R
4, R
5, R
6, R
7Identical or different, represent the C of hydrogen atom, replacement or non-replacement respectively
1-12The C of alkyl, replacement or non-replacement
1-12The C of alkoxyl group, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical.
The synthetic method of The compounds of this invention may further comprise the steps:
A) Terminal Acetylenes shown in the carbodiimide shown in the formula (I), the formula (II) and the benzyne precursor shown in the formula (III) are mixed, add the anhydrous tetrahydro furan dissolving;
B) add anhydrous potassium fluoride and anhydrous 18-hat-6, react under the room temperature;
C) reaction mixture to step b) carries out aftertreatment;
Wherein,
R
1, R
2Identical or different, expression replaces or the C of non-replacement respectively
1-12The C of alkyl, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical,
R
3Represent that functional groups such as hydrogen atom, halogen, pseudohalogen, nitro, trifluoromethyl, carbonyl, ester group, amide group replace or the C of non-replacement
1-12The C of alkyl, replacement or non-replacement
1-12The C of alkoxyl group, replacement or non-replacement
2-12The C of alkoxy carbonyl, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical,
R
4, R
5, R
6, R
7Identical or different, represent the C of hydrogen atom, replacement or non-replacement respectively
1-12The C of alkyl, replacement or non-replacement
1-12The C of alkoxyl group, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical.
About the used solvent of synthetic method, preferred anhydrous tetrahydro furan.
Synthetic method of the present invention, preferred 25 ℃ of the temperature of reaction of step a).
Synthetic method of the present invention, step b) is reacted 9h under 25 ° of C.
About the used active fluorine ions of synthetic method, be preferably villiaumite and crown ether, preferred, select Potassium monofluoride and 18-hat-6.
About synthetic method used solvent and fluorine source, anhydrous tetrahydro furan can substitute with anhydrous acetonitrile in the step a); When step a) was solvent with the anhydrous acetonitrile, step b) changed the anhydrous cesium fluoride of adding, reaction times 12h, but productive rate can reduce a little.
Synthetic method of the present invention, the mol ratio of preferred described benzyne precursor, carbodiimide, Terminal Acetylenes, Potassium monofluoride and 18-hat-6 is 2:1:1:(2-2.2): (2-2.2).
Synthetic method of the present invention, preferred described aftertreatment comprise that reaction solution concentrates, and concentration process adopts air distillation, underpressure distillation or evaporates with Rotary Evaporators.
Synthetic method of the present invention, preferred described last handling process is by chromatographic column separation and purification product, eluent is the mixed solvent of sherwood oil, ethyl acetate and methylene dichloride, and is preferred, and eluent is that volume ratio is a sherwood oil: ethyl acetate: methylene dichloride=40:1:1 mixed solvent.
The synthetic method of the adjacent amido aryl of 1-of the present invention substituted alkynyl imine derivative may further comprise the steps:
A) terminal alkyne shown in the carbodiimide shown in the formula (I), the formula (II) and the neighbour shown in the formula (III)-trimethyl silicon based phenol triflate are mixed, add the anhydrous tetrahydro furan dissolving;
B) with the reaction solution of Potassium monofluoride and 18-hat-6 adding step a), stirring reaction is 9 hours under the room temperature;
C) reaction solution with step b) obtains the adjacent amido aryl substituted alkynyl of 1 shown in the formula (IV) imines through aftertreatment;
The primitive reaction formula of above-mentioned reaction process is as follows:
Wherein:
R
1, R
2Identical or different, expression respectively:
Carbonatoms is 1-12 or more alkyl, such as: methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-..., undecyl, dodecyl, tridecyl ..., octadecyl etc., more preferably C
1-6Alkyl;
Carbonatoms is the cycloalkyl of 3-6, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl;
Carbonatoms is the thiazolinyl of 1-12, such as propenyl, styryl etc.;
Carbonatoms is the aryl of 6-12, such as phenyl, xenyl, naphthyl etc.;
Or carbonatoms is the heterocyclic aryl of 2-5, such as thienyl, thiazolyl, pyridyl etc.
Above-mentioned group can be substituted base and replace, and described substituting group can be common C
1-4Alkyl or alkoxyl group, C
4-6Cycloalkyl, halogen atom or the like.
R
3Expression:
Hydrogen atom
Carbonatoms is 1-12 or more alkyl, such as: methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-..., undecyl, dodecyl, tridecyl ..., octadecyl etc., more preferably C
1-6Alkyl;
Carbonatoms is the cycloalkyl of 3-6, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl;
Carbonatoms is the thiazolinyl of 1-12, such as propenyl, styryl etc.;
Carbonatoms is the aryl of 6-12, such as phenyl, xenyl, naphthyl etc.;
Or carbonatoms is the heterocyclic aryl of 2-5, such as thienyl, thiazolyl, pyridyl etc.
Above-mentioned group can be substituted base and replace, and described substituting group can be common C
1-4Alkyl or alkoxyl group, C
4-6Cycloalkyl, halogen atom, also can represent functionalization substituting groups such as pseudohalogen, nitro, trifluoromethyl, carbonyl, ester group, amide group.
R
4, R
5, R
6, R
7Identical or different, expression:
Hydrogen atom;
Carbonatoms is 1-12 or more alkyl, for example: methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, the tertiary butyl ..., undecyl, dodecyl, tridecyl ..., octadecyl etc., more preferably C
1-6The straight or branched alkyl;
Carbonatoms is the cycloalkyl of 3-6, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl;
Carbonatoms is the thiazolinyl of 1-12, such as propenyl, cyclohexenyl;
Carbonatoms is the aryl of 6-12, such as phenyl, xenyl, naphthyl etc.;
Or carbonatoms is the heterocyclic aryl of 2-5, such as thienyl, thiazolyl etc.
Above-mentioned group all can be substituted base and replace, and described substituting group can be functional groups such as halogen, pseudohalogen, nitro, trifluoromethyl, carbonyl, ester group, amide group.
Synthetic method of the present invention requires to carry out under the anhydrous and oxygen-free condition, and step is to carry out under nitrogen protection usually.
Employed fluorination reagent can be that Potassium monofluoride adds 18-hat-6 in the synthetic method of the present invention, also can be cesium fluoride.Solvent is respectively anhydrous tetrahydro furan or anhydrous acetonitrile.This tetrahydrofuran (THF) useful commercial reagent is back to mazarine through sodium-benzophenone before using and steams; Also can be the commercialization acetonitrile, after hydrolith refluxed 9 hours, under nitrogen protection, steam before using.
Adding 18-hat-6 with Potassium monofluoride in the synthetic method of the present invention is fluorination reagent, and tetrahydrofuran (THF) is that the reaction times of solvent is fluorination reagent than with the cesium fluoride, and acetonitrile is that the reaction times of solvent is short, and productive rate is higher.
The mol ratio preferable range of various reaction raw materials of the present invention or reagent is as shown in table 1:
The preferred molar ratio of various reaction raw materials of table 1. or reagent
| Raw material or reagent | Carbodiimide | Terminal Acetylenes | The benzyne precursor | KF | 18-hat-6 | THF |
| Molar equivalent | 1 | 1 | 2 | 2-2.2 | 2-2.2 | Arbitrarily |
The inventive method is not particularly limited the ratio of carbodiimide compound and tetrahydrofuran (THF), as long as reaction solution is evenly stirred, the carbodiimide compound of preferred 1mmol is dissolved in the ether solvent of volume greater than 3mL.
Use Potassium monofluoride and 18-hat-6 to provide active fluorine ions in the step b) of the present invention, it can make benzyne precursor converted in-situ is that benzyne participates in reaction.Therefore the adding molar equivalent of Potassium monofluoride and 18-hat-6 is for answering the equivalents of a little higher than benzyne.
The reaction times of the inventive method step a) is different because of the difference of substrate kind, and disappearing with the detection of benzyne precursor is as the criterion.Reaction in the general 9-12 of step a) hour finishes.
Step b) of the present invention is at room temperature reacted and is got final product, and also can adopt oil bath (for example silicone oil, paraffin wet goods) or other modes to heat when room temperature is too low, as long as keep temperature of reaction about 25 ° of C.
The simple before this reaction solution of aftertreatment concentrates, and the reaction solution concentration process can adopt Rotary Evaporators to concentrate.Product after concentrating is carried out purifying, and described purge process can be made eluent with certain polar solvent, and the chromatographic column separation gets final product.Selected eluent has certain difference according to the opposed polarity of product.Generally speaking, to select volume ratio for use be sherwood oil to eluent: ethyl acetate: methylene dichloride=40:1:1 mixed solvent.The chromatographic column of using such as laboratory silicagel column commonly used or high performance liquid chromatography etc.
On the other hand, the present invention also provides The compounds of this invention becoming cycloisomerisation to generate the application of condensed ring pyrroline derivative under cuprous salt catalysis.
The compounds of this invention alkynyl imines has purposes widely in the organic synthesis field, can be in order to synthesizing heterocyclic compounds, molecule in order to synthetic biologically active, in order to synthetic known and unknown compound, be used for the synthetic and exploitation of medicine, be used for the synthesis of biologically active molecule, be used for synthetic known and unknown type material.
The present invention utilizes carbodiimide, Terminal Acetylenes, benzyne precursor and active fluorine ions to prepare the adjacent amido aryl of 1-substituted alkynyl imine derivative, productive rate is higher, synthetic method is scientific and reasonable, thereby provides one synthetic to have a universal method of multiple substituent alkynyl imine derivative.This method raw material is easy to get, and is applied widely, high isolated yield, and experimental installation and operation is simple is convenient to further Application and Development.
Embodiment
Further describe the present invention below in conjunction with embodiment, but the scope that does not limit the present invention in any way.
Embodiment 1---(the R of compound shown in the preparation formula IVa
1=R
2=Cy, R
3=Ph, R
4=R
5=R
6=R
7=H):
IVa
Under nitrogen protection, in the reaction tubes of 25mL, add the silica-based phenol triflate of the adjacent front three of 2mmol, 1mmolN, N '-dicyclohexylcarbodiimide and 1mmol phenylacetylene add the dissolving of 3mL tetrahydrofuran (THF).Add 2.2mmol anhydrous potassium fluoride and 2.2mmol18-hat-6 then, room temperature (25 ℃) reaction 9 hours.The reaction soln color is by colourless flavescence.Concentration of reaction solution, the silicagel column decolouring separates, use sherwood oil: ethyl acetate: the mixed solvent of methylene dichloride=40:1:1 is made eluent, obtain alkynyl imine derivative N-{1-[2-(N-cyclohexyl-N-phenyl) phenyl]-3-phenyl-2-propynyl thiazolinyl }-hexahydroaniline 359mg(purity〉98%, yellow oily), isolated yield 78%.The nuclear magnetic data of this compound is as follows:
1HNMR (400MHz, CD
2Cl
2, Me
4Si): δ 1.15-1.47 (m, 10H, 5CH
2), 1.57-1.81 (m, 8H, 4CH2), 2.00-2.14 (m, 2H, 1CH
2), 3.80-3.90 (m, 2H, 2CH), 6.53-6.64 (m, 3H, 3CH), 6.96-6.98 (m, 2H, 2CH), 7.05-7.14 (m, 3H, 3CH), 7.19-7.29 (m, 3H, 3CH), 7.33-7.47 (m, 2H, 2CH), 7.67 (d, J=7.6Hz, 1H, 1CH).
13CNMR (100MHz, CD
2Cl
2, Me
4Si): δ 25.15 (s, 2CH
2), 26.25 (s, 1CH
2), 26.38 (s, 1CH
2), 26.54 (s, 2CH
2), 31.62 (s, 2CH
2), 33.50 (s, 2CH
2), 58.38 (s, 1CH), 64.30 (s, 1CH), 83.45 (s, 1quat.C), 96.15 (s, 1quat.C), 115.27 (s, 2CH), 116.81 (s, 1CH), 122.42 (s, 1quat.C), 127.17 (s, 1CH), 128.54 (s, 2CH), 128.96 (s, 2CH), 129.36 (s, 1CH), 130.72 (s, 1CH), 130.77 (s, 1CH), 132.37 (s, 2CH), 132.64 (s, 1CH), 141.17 (s, 1quat.C), 142.90 (s, 1quat.C), 149.14 (s, 1quat.C), 149.48 (s, 1quat.C).
Embodiment 2---(the R of compound shown in the preparation formula IVb
1=R
2=
iPr, R
3=4-MeO-Ph, R
4=R
5=R
6=R
7=H):
IVb
Under nitrogen protection, in the reaction tubes of 25mL, add the silica-based phenol triflate of the adjacent front three of 2mmol, 1mmolN, N '-DIC and 1mmol add the dissolving of 3mL tetrahydrofuran (THF) to anisole acetylene.Add 2.2mmol anhydrous potassium fluoride and 2.2mmol18-hat-6 then, room temperature (25 ℃) reaction 9 hours.The reaction soln color is by colourless flavescence.Concentration of reaction solution, the silicagel column decolouring separates, use sherwood oil: ethyl acetate: the mixed solvent of methylene dichloride=40:1:1 is made eluent, obtain N-{1-[2-(N-sec.-propyl-N-phenyl) phenyl]-3-(4-p-methoxy-phenyl)-2-propynyl thiazolinyl }-Isopropylamine 337mg(purity〉98%, yellow oily), isolated yield 82%.The nuclear magnetic data of this compound is as follows:
1HNMR (400MHz, CD
2Cl
2, Me
4Si): δ 1.14-1.19 (m, 12H, 4CH
3), 3.75 (s, 3H, 1CH
3), 4.15-4.22 (m, 1H, 1CH), 4.25-4.32 (m, 1H, 1CH), 6.56-6.58 (m, 2H, 2CH), 6.72-6.74 (m, 2H, 2CH), 6.92-6.94 (m, 2H, 2CH), and 7.07-7.17 (m, 4H, 4CH), 7.31-7.34 (m, 1H, 1CH), 7.41-7.45 (m, 1H, 1CH), 7.66-7.67 (m, 1H, 1CH).
13CNMR (100MHz, CD
2Cl
2, Me
4Si): δ 20.90 (s, 2CH
3), 23.18 (s, 2CH
3), 49.59 (s, 1CH), 55.64 (s, 1CH
3), 55.74 (s, 1CH), 82.32 (s, 1quat.C), 97.03 (s, 1quat.C), 114.20 (s, 2CH), 115.68 (s, 2CH), 117.00 (s, 1quat.C), 127.10 (s, 1CH), 128.95 (s, 2CH), 129.73 (s, 1CH), 130.73 (s, 1CH), 130.77 (s, 1CH), 132.11 (s, 1CH), 133.98 (s, 2CH), 140.84 (s, 1quat.C), 142.78 (s, 1quat.C), 149.09 (s, 1quat.C), 149.88 (s, 1quat.C), 160.77 (s, 1quat.C).
Embodiment 3---(the R of compound shown in the preparation formula IVc
1=R
2=
iPr, R
3=4-HCC-Ph, R
4=R
5=R
6=R
7=H):
IVc
Under nitrogen protection, in the reaction tubes of 25mL, add the silica-based phenol triflate of the adjacent front three of 2mmol, 1mmolN, N '-DIC and 1mmol1, the 4-diacetylene-benzene adds the dissolving of 3mL tetrahydrofuran (THF).Add 2.2mmol anhydrous potassium fluoride and 2.2mmol18-hat-6 then, room temperature (25 ℃) reaction 9 hours.The reaction soln color is by colourless flavescence.Concentration of reaction solution, the silicagel column decolouring separates, use sherwood oil: ethyl acetate: the mixed solvent of methylene dichloride=40:1:1 is made eluent, obtain N-{1-[2-(N-sec.-propyl-N-phenyl) phenyl]-3-(4-ethynyl phenyl)-2-propynyl thiazolinyl }-Isopropylamine 316mg(purity〉98%, yellow oily), isolated yield 78%.The nuclear magnetic data of this compound is as follows:
1HNMR (400MHz, CD
2Cl
2, Me
4Si): δ 1.14-1.17 (m, 12H, 4CH
3), 3.22 (s, 1H, 1CH), 4.14-4.20 (m, 1H, 1CH), 4.24-4.31 (m, 1H, 1CH), 6.54-6.65 (m, 3H, 3CH), 6.90-6.92 (m, 2H, 2CH), and 7.05-7.14 (m, 3H, 3CH), 7.30-7.38 (m, 3H, 3CH), 7.44-7.48 (m, 1H, 1CH), 7.69 (d, J=7.3Hz, 1H, 1CH).
13CNMR (100MHz, CD
2Cl
2, Me
4Si): δ 20.84 (s, 2CH
3), 23.24 (s, 2CH
3), 49.56 (s, 1CH), 55.96 (s, 1CH), 79.56 (s, 1CH), 83.26 (s, 1quat.C), 84.78 (s, 1quat.C), 95.27 (s, 1quat.C), 115.52 (s, 2CH), 117.03 (s, 1CH), 122.81 (s, 1quat.C), 129.93 (s, 1quat.C), 127.25 (s, 1CH), 129.00 (s, 2CH), 130.69 (s, 1CH), 130.94 (s, 1CH), 132.15 (s, 2CH), 132.19 (s, 2CH), 132.24 (s, 1CH), 140.83 (s, 1quat.C), 142.68 (s, 1quat.C), 149.01 (s, 1quat.C), 149.11 (s, 1quat.C).
Embodiment 4---(the R of compound shown in the preparation formula IVd
1=R
2=
iPr, R
3=4-NC-Ph, R
4=R
5=R
6=R
7=H):
IVd
Under nitrogen protection, in the reaction tubes of 25mL, add the silica-based phenol triflate of the adjacent front three of 2mmol, 1mmolN, N '-DIC and 1mmol add the dissolving of 3mL tetrahydrofuran (THF) to the itrile group phenylacetylene.Add 2.2mmol anhydrous potassium fluoride and 2.2mmol18-hat-6 then, room temperature (25 ℃) reaction 9 hours.The reaction soln color is by colourless flavescence.Concentration of reaction solution, the silicagel column decolouring separates, use sherwood oil: ethyl acetate: the mixed solvent of methylene dichloride=40:1:1 is made eluent, obtain N-{1-[2-(N-sec.-propyl-N-phenyl) phenyl]-3-(4-itrile group phenyl)-2-propynyl thiazolinyl }-Isopropylamine 320mg(purity〉98%, yellow oily), isolated yield 79%.The nuclear magnetic data of this compound is as follows:
1HNMR (400MHz, CD
2Cl
2, Me
4Si): δ 1.14-1.19 (m, 12H, 4CH3), 4.15-4.30 (m, 2H, 2CH), and 6.54-6.64 (m, 3H, 3CH), 6.95-6.98 (m, 2H, 2CH), 7.04-7.08 (m, 2H, 2CH), 7.13-7.16 (m, 1H, 1CH), 7.37-7.40 (m, 1H, 1CH), 7.46-7.48 (m, 1H, 1CH), 7.70-7.72 (m, 1H, 1CH).
13CNMR (100MHz, CD
2Cl
2, Me
4Si): δ 20.75 (s, 2CH
3), 23.26 (s, 2CH
3), 49.64 (s, 1CH), 56.19 (s, 1CH), 86.42 (s, 1quat.C), 93.88 (s, 1quat.C), 112.51 (s, 1quat.C), 115.48 (s, 2CH), 117.11 (s, 1CH), 118.68 (s, 1quat.C), 127.02 (s, 1quat.C), 127.44 (s, 1CH), 129.07 (s, 2CH), 130.69 (s, 1CH), 131.20 (s, 1CH), 132.14 (s, 2CH), 132.44 (s, 1CH), 132.67 (s, 2CH), 140.75 (s, 1quat.C), 142.66 (s, 1quat.C), 148.73 (s, 1quat.C), 149.21 (s, 1quat.C).
Embodiment 5---(the R of compound shown in the preparation formula IVe
1=R
2=
iPr, R
3=4-PhCO-Ph, R
4=R
5=R
6=R
7=H):
IVe
Under nitrogen protection, in the reaction tubes of 25mL, add the silica-based phenol triflate of the adjacent front three of 2mmol, 1mmolN, N '-DIC and 1mmol1-phenyl-2-propine-1-ketone adds the dissolving of 3mL tetrahydrofuran (THF).Add 2.2mmol anhydrous potassium fluoride and 2.2mmol18-hat-6 then, room temperature (25 ℃) reaction 9 hours.The reaction soln color is by colourless crimson.Concentration of reaction solution; the silicagel column decolouring separates; use sherwood oil: ethyl acetate: the mixed solvent of methylene dichloride=40:1.5:1.5 is made eluent; obtain N-{1-[2-(N-sec.-propyl-N-phenyl) phenyl]-3-benzoyl-2-propynyl thiazolinyl }-Isopropylamine 343mg(purity〉98%; the scarlet oily), isolated yield 84%.The nuclear magnetic data of this compound is as follows:
1HNMR (400MHz, CD
2Cl
2, Me
4Si): δ 1.11 (d, J=6.1Hz, 6H, 2CH
3), 1.18 (d, J=6.4Hz, 6H, 2CH
3), 4.02-4.09 (m, 1H, 1CH), 4.25-4.32 (m, 1H, 1CH), and 6.43-6.51 (m, 3H, 3CH), 6.91-6.95 (m, 2H, 2CH), and 7.18-7.20 (m, 1H, 1CH), 7.18-7.20 (m, 1H, 1CH), and 7.37-7.53 (m, 4H, 4CH), 7.58-7.62 (m, 1H, 1CH), 7.76 (d, J=7.7Hz, 1H, 1CH), 7.85 (d, J=7.9Hz, 1H, 1CH).
13CNMR (100MHz, CD
2Cl
2, Me
4Si): δ 20.98 (s, 2CH
3), 23.31 (s, 2CH
3), 49.32 (s, 1CH), 56.83 (s, 1CH), 85.00 (s, 1quat.C), 91.90 (s, 1quat.C), 115.43 (s, 2CH), 117.51 (s, 1CH), 127.28 (s, 1CH), 128.93 (s, 2CH), 128.97 (s, 2CH), 129.76 (s, 2CH), 130.51 (s, 1CH), 131.55 (s, 1CH), 131.74 (s, 1CH), 134.59 (s, 1CH), 136.62 (s, 1quat.C), 139.37 (s, 1quat.C), 142.52 (s, 1quat.C), 146.77 (s, 1quat.C), 148.36 (s, 1quat.C), 177.19 (s, 1quat.C).
Embodiment 6---(the R of compound shown in the preparation formula IVf
1=R
2=
iPr, R
3=3-thienyl, R
4=R
5=R
6=R
7=H):
IVf
Under nitrogen protection, in the reaction tubes of 25mL, add the silica-based phenol triflate of the adjacent front three of 2mmol, 1mmolN, N '-DIC and 1mmol3-thiophene acetylene add the dissolving of 3mL tetrahydrofuran (THF).Add 2.2mmol anhydrous potassium fluoride and 2.2mmol18-hat-6 then, room temperature (25 ℃) reaction 9 hours.The reaction soln color is by colourless flavescence.Concentration of reaction solution, the silicagel column decolouring separates, use sherwood oil: ethyl acetate: the mixed solvent of methylene dichloride=40:1:1 is made eluent, obtain N-{1-[2-(N-sec.-propyl-N-phenyl) phenyl]-3-(3-thienyl)-2-propynyl thiazolinyl }-Isopropylamine 290mg(purity〉98%, yellow oily), isolated yield 75%.The nuclear magnetic data of this compound is as follows:
1HNMR (400MHz, CD
2Cl
2, Me
4Si): δ 1.14-1.17 (m, 12H, 4CH
3), 4.13-4.19 (m, 1H, 1CH), 4.24-4.31 (m, 1H, 1CH), 6.56-6.58 (m, 2H, 2CH), 6.64 (t, J=7.2Hz, 1H, 1CH), 6.73 (d, J=4.7Hz, 1H, 1CH), 6.96 (s, 1H, 1CH), 7.07-7.12 (m, 3H, 3CH), 7.15-7.17 (m, 1H, 1CH), 7.34 (t, J=7.4Hz, 2H, 2CH), 7.44 (t, J=7.5Hz, 2H, 2CH), 7.68 (d, J=6.8Hz, 2H, 2CH).
13CNMR (100MHz, CD
2Cl
2, Me
4Si): δ 20.80 (s, 2CH
3), 23.25 (s, 2CH
3), 49.54 (s, 1CH), 55.78 (s, 1CH), 82.81 (s, 1quat.C), 91.33 (s, 1quat.C), 115.56 (s, 2CH), 116.95 (s, 1CH), 121.43 (s, 1quat.C), 125.69 (s, 1CH), 127.17 (s, 1CH), 128.91 (s, 2CH), 130.14 (s, 1CH), 130.65 (s, 1CH), 130.79 (s, 1CH), 130.80 (s, 1CH), 132.18 (s, 1CH), 140.95 (s, 1quat.C), 142.68 (s, 1quat.C), 149.12 (s, 1quat.C), 149.18 (s, 1quat.C).
Embodiment 7---(the R of compound shown in the preparation formula IVg
1=R
2=
iPr, R
3=
nBu, R
4=R
5=R
6=R
7=H):
IVg
Under nitrogen protection, in the reaction tubes of 25mL, add the silica-based phenol triflate of the adjacent front three of 2mmol, 1mmolN, N '-DIC and 1mmol1-hexin add the dissolving of 3mL tetrahydrofuran (THF).Add 2.2mmol anhydrous potassium fluoride and 2.2mmol18-hat-6 then, room temperature (25 ℃) reaction 9 hours.The reaction soln color is by colourless flavescence.Concentration of reaction solution, the silicagel column decolouring separates, and use sherwood oil: ethyl acetate: the mixed solvent of methylene dichloride=40:1:1 is made eluent, obtains N-{1-[2-(N-sec.-propyl-N-phenyl) phenyl]-2-heptyne base thiazolinyl }-Isopropylamine 253mg(purity〉98%, yellow oily), isolated yield 70%.The nuclear magnetic data of this compound is as follows:
1HNMR (400MHz, CD
2Cl
2, Me
4Si): δ 0.83 (t, J=7.0Hz, 3H, 1CH
3), 1.05 (d, J=6.3Hz, 6H, 2CH
3), 1.15 (d, J=6.6Hz, 6H, 2CH
3), 1.25-1.27 (m, 4H, 2CH
2), 1.96 (d, J=6.7Hz, 2H, 1CH
2), 3.96-4.06 (m, 1H, 1CH), 4.19-4.28 (m, 1H, 1CH), 6.48-6.50 (m, 2H, 2CH), and 6.57-6.60 (m, 1H, 1CH), 7.04-7.11 (m, 3H, 3CH), 7.30-7.34 (m, 1H, 1CH), 7.39-7.43 (m, 1H, 1CH), 7.56-7.58 (m, 1H, 1CH).
13CNMR (100MHz, CD
2Cl
2, Me4Si): δ 13.66 (s, 1CH
3), 19.06 (s, 1CH2), 20.96 (s, 2CH
3), 22.35 (s, 1CH
2), 23.17 (s, 2CH
3), 30.54 (s, 1CH
2), 49.41 (s, 1CH), 55.55 (s, 1CH), 75.05 (s, 1quat.C), 99.29 (s, 1quat.C), 115.13 (s, 2CH), 116.61 (s, 1CH), 127.08 (s, 1CH), 128.69 (s, 2CH), 130.40 (s, 1CH), 130.61 (s, 1CH), 132.24 (s, 1CH), 141.52 (s, 1quat.C), 142.34 (s, 1quat.C), 148.90 (s, 1quat.C), 149.63 (s, 1quat.C).
Embodiment 8---(the R of compound shown in the preparation formula IVh
1=R
2=
iPr, R
3=
tBu, R
4=R
5=R
6=R
7=H):
IVh
Under nitrogen protection, in the reaction tubes of 25mL, add the silica-based phenol triflate of the adjacent front three of 2mmol, 1mmolN, N '-DIC and 1mmol3,3-dimethyl butine adds the dissolving of 3mL tetrahydrofuran (THF).Add 2.2mmol anhydrous potassium fluoride and 2.2mmol18-hat-6 then, room temperature (25 ℃) reaction 9 hours.The reaction soln color is by colourless flavescence.Concentration of reaction solution, the silicagel column decolouring separates, use sherwood oil: ethyl acetate: the mixed solvent of methylene dichloride=40:1:1 is made eluent, obtain N-{1-[2-(N-sec.-propyl-N-phenyl) phenyl]-4,4-dimethyl-valerylene base thiazolinyl }-Isopropylamine 263mg(purity〉98%, yellow oily), isolated yield 73%.The nuclear magnetic data of this compound is as follows:
1HNMR (400MHz, CD
2Cl
2, Me
4Si): δ 1.03-1.05 (m, 15H, 5CH
3), 1.17 (d, J=6.6Hz, 6H, 2CH
3), 3.92-4.02 (m, 1H, 1CH), 4.19-4.28 (m, 1H, 1CH), 6.52 (d, J=8.2Hz, 2H, 2CH), 6.59 (t, J=7.2Hz, 1H, 1CH), 7.04-7.09 (m, 3H, 3CH), 7.28-7.32 (m, 1H, 1CH), 7.38-7.42 (m, 1H, 1CH), 7.56 (d, J=7.6Hz, 1H, 1CH).
13CNMR (100MHz, CD
2Cl
2, Me
4Si): δ 20.99 (s, 2CH
3), 23.00 (s, 2CH
3), 28.29 (s, 1quat.C), 30.43 (s, 3CH
3), 49.54 (s, 1CH), 55.15 (s, 1CH), 73.69 (s, 1quat.C), 106.62 (s, 1quat.C), 115.56 (s, 2CH), 116.80 (s, 1CH), 126.87 (s, 1CH), 128.76 (s, 2CH), 130.38 (s, 1CH), 130.61 (s, 1CH), 131.86 (s, 1CH), 141.14 (s, 1quat.C), 142.81 (s, 1quat.C), 148.84 (s, 1quat.C), 149.67 (s, 1quat.C).
Embodiment 9---(the R of compound shown in the preparation formula IVi
1=R
2=
iPr, R
3=cyclopropyl, R
4=R
7=H, R
5=R
6=3.4--(CH)
4-):
IVi
Under nitrogen protection, in the reaction tubes of 25mL, add 2mmol trifluoromethanesulfonic acid 3-(trimethyl silicon based)-2-naphthalene ester, 1mmolN, N '-DIC and 1mmol cyclopropyl acethlene add the dissolving of 3mL tetrahydrofuran (THF).Add 2.2mmol anhydrous potassium fluoride and 2.2mmol18-hat-6 then, room temperature (25 ℃) reaction 9 hours.The reaction soln color is by colourless flavescence.Concentration of reaction solution, the silicagel column decolouring separates, use sherwood oil: ethyl acetate: the mixed solvent of methylene dichloride=40:1:1 is made eluent, obtain N-{2-[3-(N-sec.-propyl-N-(2-naphthyl)) naphthyl]-3-cyclopropyl-2-propynyl thiazolinyl }-Isopropylamine 351mg(purity〉98%, yellow oily), isolated yield 79%.The nuclear magnetic data of this compound is as follows:
1HNMR (400MHz, CD
2Cl
2, Me
4Si): δ 0.35-0.62 (m, 4H, 2CH
2), 0.97 (d, J=6.2Hz, 6H, 2CH
3), 1.03-1.06 (m, 1H, 1CH), 1.29 (d, J=6.6Hz, 6H, 2CH
3), 3.89-3.95 (m, 1H, 1CH), 4.41-4.47 (m, 1H, 1CH), and 6.79-6.82 (m, 1H, 1CH), 6.94 (s, 1H, 1CH), 7.14 (t, J=7.4Hz, 1H, 1CH), 7.30 (t, J=7.5Hz, 1H, 1CH), 7.48-7.63 (m, 6H, 6CH), and 7.78-7.81 (m, 1H, 1CH), 7.92-7.94 (m, 1H, 1CH), 8.08 (s, 1H, 1CH).
13CNMR (100MHz, CD
2Cl
2, Me
4Si): δ 0.14 (s, 1CH), 9.01 (s, 2CH
2), 21.06 (s, 2CH
3), 23.11 (s, 2CH
3), 50.12 (s, 1CH), 55.56 (s, 1CH), 70.71 (s, 1quat.C), 102.86 (s, 1quat.C), 108.85 (s, 1CH), 119.66 (s, 1CH), 122.19 (s, 1CH), 126.20 (s, 1CH), 126.52 (s, 2CH), 127.05 (s, 1CH), 127.43 (s, 1quat.C), 127.54 (s, 1CH), 127.63 (s, 1CH), 128.07 (s, 1CH), 128.62 (s, 1CH), 130.04 (s, 1CH), 130.41 (s, 1CH), 132.40 (s, 1quat.C), 134.69 (s, 1quat.C), 135.23 (s, 1quat.C), 139.75 (s, 1quat.C), 140.15 (s, 1quat.C), 146.82 (s, 1quat.C), 149.10 (s, 1quat.C).
Embodiment 10---(the R of compound shown in the preparation formula IVj
1=
tBu, R
2=Et, R
3=Ph, R
4=R
5=R
6=R
7=H):
IVj
Under nitrogen protection, in the reaction tubes of 25mL, add the silica-based phenol triflate of the adjacent front three of 2mmol, 1mmolN-ethyl n '-tertiary butyl carbodiimide and 1mmol phenylacetylene, add the dissolving of 3mL tetrahydrofuran (THF).Add 2.2mmol anhydrous potassium fluoride and 2.2mmol18-hat-6 then, room temperature (25 ℃) reaction 9 hours.The reaction soln color is by colourless flavescence.Concentration of reaction solution, the silicagel column decolouring separates, use sherwood oil: ethyl acetate: the mixed solvent of methylene dichloride=40:1:1 is made eluent, obtain N-{1-[2-(N-ethyl-N '-phenyl) phenyl]-3-phenyl-2-propynyl thiazolinyl }-hexahydroaniline 282mg(purity〉98%, yellow oily), isolated yield 74%.The nuclear magnetic data of this compound is as follows:
1HNMR (500MHz, CD
2Cl
2, Me
4Si): δ 1.21 (t, J=7.0Hz, 3H, 1CH
3), 1.39 (s, 9H, 3CH
3), 3.66 (q, J=7.0Hz, 2H, 1CH
2), 6.64-6.67 (m, 3H, 3CH), 7.00-7.11 (m, 4H, 4CH), 7.19-7.23 (m, 3H, 3CH), 7.26-7.29 (m, 2H, 2CH), 7.38-7.41 (m, 1H, 1CH), 7.54 (d, J=7.6Hz, 1H, 1CH).
13CNMR (125MHz, CD
2Cl
2, Me
4Si): δ 12.52 (s, 1CH
3), 29.35 (s, 3CH
3), 46.45 (s, 1CH
2), 57.55 (s, 1quat.C), 85.83 (s, 1quat.C), 97.24 (s, 1quat.C), 114.79 (s, 2CH), 117.26 (s, 1CH), 122.49 (s, 1quat.C), 126.29 (s, 1CH), 128.60 (s, 2CH), 129.13 (s, 2CH), 129.50 (s, 1CH), 129.99 (s, 1CH), 130.43 (s, 1CH), 130.78 (s, 1CH), 131.81 (s, 2CH), 140.69 (s, 1quat.C), 145.12 (s, 1quat.C), 148.09 (s, 1quat.C), 148.36 (s, 1quat.C).
Synthetic application examples---compound shown in the preparation formula V
V
In the reaction tubes of 25mL, add 1mmolN-{1-[2-(N-sec.-propyl-N-phenyl) phenyl]-2-heptyne base thiazolinyl }-Isopropylamine (IVg) and 0.3mmolCuI, add 4mL exsiccant N, be stirred to CuI after the N-diethylformamide and dissolve fully.Add 0.5mL exsiccant Et
3N, 110 ℃ of lucifuge reaction 24h.System was reduced to room temperature after reaction was finished, and added 4mL water in reaction soln, and with normal hexane (4mL*3) extractive reaction liquid, merging, dry back concentrate organic extractant phase liquid.The silicagel column decolouring separates, and use sherwood oil: ethyl acetate: the mixed solvent of methylene dichloride=100:4:7 is made eluent, obtains pyrroline derivative (V) 263mg(purity〉98%, faint yellow oily), isolated yield 73%.The nuclear magnetic data of this compound is as follows:
1HNMR (400MHz, CD
2Cl
2, Me
4Si): δ=0.77-0.82 (m, 3H, 1CH
3), 1.01-1.05 (m, 3H, 1CH
21CH), 1.11-1.18 (m, 6H, 2CH
3), 1.22-1.26 (m, 3H, 1CH
21CH), 1.33 (s, 3H, 1CH
3), 2.11-2.26 (m, 2H, 1CH
2), 2.37-2.42 (m, 1H, 1CH), 2.78-2.79 (m, 1H, 1CH), 4.24-4.30 (m, 1H, 1CH), and 6.49-4.51 (m, 2H, 2CH), 6.60-6.64 (m, 1H, 1CH), 7.08-7.14 (m, 3H, 3CH), 7.33-7.47 (m, 2H, 2CH), 7.77-7.80 (m, 1H, 1CH).
13CNMR (100MHz, CD
2Cl
2, Me
4Si): δ 14.19 (s, 1CH
3), 20.78 (s, 2CH
3), 20.98 (s, 1CH
2), 25.03 (s, 1CH
3), 29.13 (s, 1CH), 33.51 (s, 1CH
2), 39.94 (s, 1CH
2), 41.48 (s, 1CH
2), 43.01 (s, 1CH), 48.94 (s, 1CH), 75.92 (s, 1quat.C), 114.54 (s, 2CH), 116.95 (s, 1CH), 127.26 (s, 1CH), 129.18 (s, 2CH), 130.82 (s, 1CH), 131.01 (s, 1CH), 132.31 (s, 1CH), 139.03 (s, 1quat.C), 142.16 (s, 1quat.C), 148.90 (s, 1quat.C), 173.14 (s, 1quat.C).
Claims (10)
1. the compound of a general formula (1) expression:
In the formula,
Ar is an aromatic nucleus, represents monocycle, encircles and heterocycle more;
R
1, R
2, R
3Identical or different with R, the C of expression replacement or non-replacement
1_12The C of alkyl, replacement or non-replacement
1_12The C of alkoxyl group, replacement or non-replacement
2-12The C of alkoxy carbonyl, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical, described substituting group comprises hydrogen atom, halogen, pseudohalogen, nitro, trifluoromethyl, carbonyl, ester group and amide group.
2. compound as claimed in claim 1 is characterized in that,
R
1, R
2Identical or different, derive from carbodiimide both sides substituting group, respectively the C of expression replacement or non-replacement
1-12The C of alkyl, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical;
R
3Derive from the Terminal Acetylenes substituting group, the C of expression replacement or non-replacement
1-12The C of alkyl, replacement or non-replacement
1-12The C of alkoxyl group, replacement or non-replacement
2-12The C of alkoxy carbonyl, replacement or non-replacement
6-12The C of last aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical, described substituting group comprises hydrogen atom, halogen, pseudohalogen, nitro, trifluoromethyl, carbonyl, ester group and amide group;
R is positioned on the aromatic nucleus, derives from the substituting group of aryne precursor, the C of expression replacement or non-replacement
1-12The C of alkyl, replacement or non-replacement
1-12The C of alkoxyl group, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical, described substituting group comprises hydrogen atom, halogen, pseudohalogen, nitro, trifluoromethyl, carbonyl, ester group and amide group.
3. compound as claimed in claim 2, it has the structure shown in the formula (IV):
Wherein,
R
1, R
2Identical or different, expression replaces or the C of non-replacement respectively
1-12The C of alkyl, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical;
R
3The C of expression replacement or non-replacement
1-12The C of alkyl, replacement or non-replacement
1-12The C of alkoxyl group, replacement or non-replacement
2-12The C of alkoxy carbonyl, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical, described substituting group comprises: hydrogen atom, halogen, pseudohalogen, nitro, trifluoromethyl, carbonyl, ester group and amide group;
R
4, R
5, R
6, R
7Identical or different, represent the C of hydrogen atom, replacement or non-replacement respectively
1-12The C of alkyl, replacement or non-replacement
1-12The C of alkoxyl group, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical.
4. the synthetic method of the described compound of claim 1 is characterized in that, comprises the following steps:
A) Terminal Acetylenes shown in the carbodiimide shown in the formula (I), the formula (II) and the benzyne precursor shown in the formula (III) are mixed, add the anhydrous tetrahydro furan dissolving;
B) add anhydrous potassium fluoride and anhydrous 18-hat-6, react under the room temperature;
Wherein,
R
1, R
2Identical or different, expression replaces or the C of non-replacement respectively
1-12The C of alkyl, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical;
R
3The C of expression replacement or non-replacement
1-12The C of alkyl, replacement or non-replacement
1-12The C of alkoxyl group, replacement or non-replacement
2-12The C of alkoxy carbonyl, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical, described substituting group comprises C
1-4Alkyl or alkoxyl group, C
4-6Cycloalkyl, halogen atom, pseudohalogen, nitro, trifluoromethyl, carbonyl, ester group and amide group;
R
4, R
5, R
6, R
7Identical or different, represent the C of hydrogen atom, replacement or non-replacement respectively
1-12The C of alkyl, replacement or non-replacement
1-12The C of alkoxyl group, replacement or non-replacement
6-12The C of aryl, non-replacement
3-7Heterocyclic radical, on heterocycle substituted C
3-7Heterocyclic radical.
5. synthetic method as claimed in claim 4 is characterized in that, described step b) is reacted 9h down at 25 ℃.
6. synthetic method as claimed in claim 4 is characterized in that, described step a) anhydrous tetrahydro furan can substitute with anhydrous acetonitrile; When step a) was solvent with the anhydrous acetonitrile, step b) changed the anhydrous cesium fluoride of adding, reaction times 12h.
7. synthetic method as claimed in claim 4 is characterized in that, the mol ratio of described benzyne precursor, carbodiimide, Terminal Acetylenes, Potassium monofluoride and 18-hat-6 is 2: 1: 1: 2-2.2:2-2.2.
8. synthetic method as claimed in claim 4, it is characterized in that, comprise that also the reaction mixture to step b) carries out aftertreatment, described aftertreatment comprises that reaction solution concentrates, concentration process adopts air distillation, underpressure distillation or evaporates with Rotary Evaporators, described aftertreatment comprises also that by chromatographic column separation and purification product eluent is that volume ratio is a sherwood oil: ethyl acetate: methylene dichloride=40:1: 1 mixed solvent.
9. each described compound of the 1-3 of claim is at synthetic 1-pyrroline or contain the application of the medicine and the bioactive molecules of 1-pyrroline.
Each described compound of the 1-3 of claim synthetic nitrogen-containing heterocycle compound and bioactive molecules, derivative reaction, type material research and development, new compound synthetic with and in organic synthesis, be used as the application of synthetic intermediate.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005330413A (en) * | 2004-05-21 | 2005-12-02 | Fuji Photo Film Co Ltd | Coating liquid for film formation, insulating film obtained using coating liquid and electronic device comprising the same |
| CN101643450A (en) * | 2009-09-01 | 2010-02-10 | 北京大学 | Synthesis method for multi substituted 2, 3-dihydro-4(1H)-pyrimidin thionone |
| CN101665470A (en) * | 2009-09-18 | 2010-03-10 | 中国科学院上海有机化学研究所 | Method for synthesizing cyclic sulphoxide imine, sulfenamide and sulfamide by stereospecificty |
| CN101798282A (en) * | 2010-03-30 | 2010-08-11 | 中国科学院上海有机化学研究所 | Multi-substituted fluorine-containing pyridine |
| WO2013038427A1 (en) * | 2011-09-12 | 2013-03-21 | Council Of Scientific & Industrial Research | ARYLATED β-DICARBOIMYL COMPOUNDS AND PROCESS FOR THE PREPARATION THEREOF |
-
2013
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005330413A (en) * | 2004-05-21 | 2005-12-02 | Fuji Photo Film Co Ltd | Coating liquid for film formation, insulating film obtained using coating liquid and electronic device comprising the same |
| CN101643450A (en) * | 2009-09-01 | 2010-02-10 | 北京大学 | Synthesis method for multi substituted 2, 3-dihydro-4(1H)-pyrimidin thionone |
| CN101665470A (en) * | 2009-09-18 | 2010-03-10 | 中国科学院上海有机化学研究所 | Method for synthesizing cyclic sulphoxide imine, sulfenamide and sulfamide by stereospecificty |
| CN101798282A (en) * | 2010-03-30 | 2010-08-11 | 中国科学院上海有机化学研究所 | Multi-substituted fluorine-containing pyridine |
| WO2013038427A1 (en) * | 2011-09-12 | 2013-03-21 | Council Of Scientific & Industrial Research | ARYLATED β-DICARBOIMYL COMPOUNDS AND PROCESS FOR THE PREPARATION THEREOF |
Non-Patent Citations (2)
| Title |
|---|
| BERNARD G. VAN DEN HOVEN等: "Innovative Synthesis of 4-Carbaldehydepyrrolin-2-ones by Zwitterionic Rhodium Catalyzed Chemo- and Regioselective Tandem Cyclohydrocarbonylation/CO Insertion of R-Imino Alkynes", 《J. AM. CHEM. SOC》 * |
| FENG SHA等: "A Multicomponent Reaction of Arynes, Isocyanides, and TerminalAlkynes: Highly Chemo- and Regioselective Synthesis of Polysubstituted Pyridines and Isoquinolines", 《ANGEW.CHEM.INT.ED.》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105152967A (en) * | 2015-09-28 | 2015-12-16 | 方美兰 | Synthesis method for medical intermediate trifluoromethyl substituted cyclohexane compound |
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