CN107382769B - A kind of 1- aryl -3- azido -4,4, the preparation method of the fluoro- 1- butene compounds of 4- tri- - Google Patents
A kind of 1- aryl -3- azido -4,4, the preparation method of the fluoro- 1- butene compounds of 4- tri- Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C247/00—Compounds containing azido groups
- C07C247/02—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton
- C07C247/08—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton being unsaturated
- C07C247/10—Compounds containing azido groups with azido groups bound to acyclic carbon atoms of a carbon skeleton being unsaturated and containing rings
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- 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
- C07D307/38—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 substituted hydrocarbon radicals attached to ring carbon atoms
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Abstract
The present invention relates to a kind of 1- aryl -3- azido -4,4, the preparation method of the fluoro- 1- butene compounds of 4- tri- belongs to field of compound preparation.The preparation method of a kind of 1- aryl -3- azido -4,4, the fluoro- 1- butylene of 4- tri- in the presence of catalyst and additive, is reacted by following reaction equations using compound described in general formula II and trimethyl silicane nitrine as raw material, obtains compound shown in general formula I.
Description
Technical field
The present invention relates to a kind of 1- aryl -3- azido -4,4, the preparation method of the fluoro- 1- butene compounds of 4- tri- belongs to
Field of compound preparation.
Background technique
Organic azide is reaction intermediate and the synthesis important block of nitrogenous compound important in organic synthesis
Block.Such as organic azide can be converted to nitrogen-containing heterocycle structure important in amine, isocyanates and drug molecule
(Chem.Eur.J.2009,15,7830.；Angew.Chem.Int.Ed.2005,44,5188.).In recent years, in clickization
The cycloaddition reaction of field, copper catalysis organic azide and alkynes also achieves a series of important achievements
(Chem.Rev.2009,109,5620.；Chem.Soc.Rev.2010,39,1536.).At the same time, many organic nitrines
Close object it is antiviral and in terms of show good bioactivity (J.Med.Chem.1993,36,2470.；
Molecules 2013,18,1477.).Therefore, azido group is introduced in organic molecule to have great importance and be worth.
It is well known that introducing CF in organic molecule due to the special nature of fluorine element3The object of molecule can be significantly changed
Reason, chemistry and biological property (Chem.Rev.2016,116,422).Therefore, if containing CF in molecule simultaneously3And N3It will
It is a very valuable organic synthesis building block.It can construct containing CF3Bioactive molecule (ACS
Cent.Sci.2016,2,715.).However, synthesis contains CF at present3The report of substituted organic azide is fewer
(J.Am.Chem.Soc.2003,125,6900.；Angew.Chem.Int.Ed.2014,53,1881.；ACS Catal.2015,
5,2826.；Org.Lett.2014,16,3896.).Moreover, these methods have used expensive, unstable CF3Methylation examination
Agent significantly limits the application of such methods.
Summary of the invention
The object of the present invention is to provide a kind of organic amines that at low cost, raw material is easy to get extensively directly as catalyst, with three
Methyl silicon nitrine is Azide reagenl, replaces enol sulphonic acid ester (compound shown in general formula II) for raw material with trifluoromethyl, efficiently,
Easy, economic one-step synthesis 1- aryl -3- azido -4,4, tri- fluoro- 1- butene compounds (compound shown in general formula I) of 4-
Method.In addition, 1- aryl -3- azido -4,4, the fluoro- 1- butene compounds of 4- tri-, can be with as good organic synthesis building block
It is converted into the compounds such as amine, allyl amine, the triazole that corresponding trifluoromethyl replaces.
A kind of 1- aryl -3- azido -4,4, the preparation method of the fluoro- 1- butene compounds of 4- tri-, to change shown in general formula II
Closing object and trimethyl silicane azido compound is raw material, in the presence of catalyst and additive in solvent by following reaction equations into
Row reaction, obtains compound shown in general formula I,
Wherein,
Ar is selected fromWherein X is derived from O, S, N (CH3)；N=1,
2,3,4,5, it is link position at wave；
R is selected from H, C1~C6 alkyl, phenyl, halogen, trifluoromethyl, trifluoromethoxy, C1~C4 alkoxy, C2~C5 ester
Base, cyano；
The catalyst is triethylamine, diisopropylethylamine, 1,8- diazabicylo, 11 carbon -7- alkene, 1,5- diaza
Bicyclic [4.3.0] -5- nonene, bicyclic (4.4.0) the decyl- 5- alkene of 1,5,7- tri- nitrine, Isosorbide-5-Nitrae-diazabicylo [2.2.2] octane,
At least one of 4-dimethylaminopyridine, tetramethylethylenediamine, heptamethyldisilazane；
The additive is sodium bicarbonate, saleratus, sodium carbonate, potassium carbonate, potassium fluoride, lithium fluoride, cesium fluoride, fluorination
At least one of sodium；
Solvent of the present invention be preferably glycol dimethyl ether, tetrahydrofuran, Isosorbide-5-Nitrae-dioxane, 1,2- dichloroethanes,
At least one of carbon tetrachloride, toluene, acetonitrile, n,N-Dimethylformamide, dimethyl sulfoxide, N-Methyl pyrrolidone.
Solvent of the present invention, dosage meet reaction and require, the amount of compound shown in preferred formula II and solvent
The ratio between be 1mmol:(5~15) mL.
Unless otherwise stated, term used herein has following meanings.
Term " alkyl " used herein includes straight chained alkyl and branched alkyl.Such as refer to single alkyl such as " methyl ",
Straight chained alkyl is then only refered in particular to, such as refers to that single branched alkyl such as " isopropyl ", then only refers in particular to branched alkyl.For example, " C4 or less alkane
Base " includes methyl, ethyl, n-propyl, isopropyl, normal-butyl and tert-butyl etc..Similar rule is also suitable in this manual
The other groups used.
Term " halogen " used herein includes fluorine, chlorine, bromine, iodine.
C2~C5 ester group described herein is the group having the following structure :-COOR, wherein R is C1~C4 alkyl.
C1~C4 alkoxy described herein is the group having the following structure :-O-M1, wherein M1For C1~C4 alkyl,
Such as methoxyl group, ethyoxyl, propoxyl group, isopropoxy, butoxy, tert-butoxy.
It is described in above scheme(n=1,2,3,4,5) are link position at wave, wherein (R)nIn, n
=1,2,3,4,5 refer to that substitution of the R on phenyl can replace for monosubstituted or multidigit, can replace for 1,2,3,4 or 5.It is when n=1
Monosubstituted, mono-substituted substitution position can be 2,3 or 4；When n=2,3,4 or 5, for multidigit replace, wherein n=2 be it is disubstituted,
Disubstituted substitution position is 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, 3,5-；N=3 is three substitutions, and trisubstituted substitution position is 2,
3,4-, 2,3,5-, 2,3,6-, 3,4,5-.
1- aryl -3- azido -4,4 of the present invention, the fluoro- 1- butene compounds of 4- tri-, Ar are selected fromWherein X is derived from O, S, N (CH3)；N=1,2,3,4,5；
Further,Wherein X is derived from O；N=1,2,3,4,5 are link position at wave；
R is selected from H, C1~C6 alkyl, phenyl, halogen, trifluoromethyl, trifluoromethoxy, C1~C4 alkoxy, C2~C5 ester
Base, cyano；Further, R is selected from H, methyl, isopropyl, phenyl, halogen, trifluoromethyl, methoxyl group, ethoxycarbonyl, cyano；
1- aryl -3- azido -4,4 of the present invention, the fluoro- 1- butene compounds preparation method of 4- tri-, the additive
The amount of substance be 1.2~3 times of amount of combinations of materials shown in general formula II；
1- aryl -3- azido -4,4 of the present invention, the fluoro- 1- butene compounds preparation method of 4- tri-, the catalyst
The amount of substance be 0.05~0.3 times of amount of combinations of materials shown in general formula II；
1- aryl -3- azido -4,4 of the present invention, the fluoro- 1- butene compounds preparation method of 4- tri-, the trimethyl
The amount of the substance of nitrine is 1~5 times, preferably 2~5 times shown in general formula II；
1- aryl -3- azido -4,4 of the present invention, the fluoro- 1- butene compounds preparation method of 4- tri- are preferably above-mentioned anti-
The reaction temperature answered is 25 DEG C~65 DEG C, and the reaction time is 6h~48h, preferably 6h~for 24 hours.
A preferred technical solution of the invention are as follows:
A kind of 1- aryl -3- azido -4,4, the fluoro- 1- butene compounds preparation method of 4- tri-, with chemical combination shown in general formula II
Object and trimethyl azide are raw material, are reacted, are obtained logical by following reaction equations in solvent in the presence of catalyst and additive
Compound shown in Formulas I, wherein reaction temperature is 65 DEG C, and the reaction time is 6h~48h.
Wherein,
Ar is selected fromWherein X is derived from O, S, N (CH3)；N=1,2,
3,4,5；
R is selected from H, methyl, isopropyl, phenyl, halogen, trifluoromethyl, methoxyl group, ethoxycarbonyl or cyano；
The catalyst is at least one of triethylamine, diisopropylethylamine；
The additive is at least one of sodium bicarbonate, saleratus, potassium fluoride；
The solvent is preferably at least one of glycol dimethyl ether, tetrahydrofuran, Isosorbide-5-Nitrae-dioxane, toluene.
The specific structure of each raw material compound substituent group in above-mentioned reaction equation is listed in table 1.But it is not limited only to these
Structure.
Table 1
(note: being link position at wave)
Table 2 list the structure of particular compound 1~18 that the present invention synthesizes, physical property and1H NMR data, but this
Invention is not limited in these compounds.
Table 2
The method of the invention directly uses cheap, commercially available organic amine as catalyst, is 1- aryl -3- azido -
The synthesis of 4,4,4- tri- fluoro- 1- butene compounds provides a kind of method of convenience, low cost, while avoiding using expensive
, unstable trifluoromethyl reagent.
Specific embodiment
Following non-limiting embodiments can with a person of ordinary skill in the art will more fully understand the present invention, but not with
Any mode limits the present invention.
Test method described in following embodiments is unless otherwise specified conventional method；The reagent and material, such as
Without specified otherwise, commercially obtain.
Embodiment 1
1- phenyl -3- azido -4,4, the preparation (compound 1) of the fluoro- 1- butylene of 4- tri-
At room temperature, 4- phenyl -2- trifluoromethanesulfonate -1,1 is sequentially added into Schlenk bottles of 25mL that argon gas is protected,
The fluoro- 2- butylene 167mg (0.5mmol) of 1- tri-, trifluoromethanesulfonate -1 anhydrous solvent glycol dimethyl ether 5mL, 4- phenyl -2-,
The saleratus 60mg (0.6mmol) of 1,1- tri- 1.2 times of moles of fluoro- 2- butylene, 4- phenyl -2- trifluoromethanesulfonate -1,1,
The trimethyl azide 0.14mL (1.0mmol) of tri- 2 times of moles of fluoro- 2- butylene of 1-, 4- phenyl -2- trifluoromethanesulfonate -1,1,
The Triethylamine catalyst 0.76mL (10mg/mL, 0.075mmol) of tri- 0.15 times of mole of fluoro- 2- butylene of 1-, is placed in 65 DEG C of reactions
12 hours.It is extracted with ethyl acetate (3 × 10mL), merges organic phase with saturated common salt water washing (2 × 10mL) afterwards with anhydrous sulphur
Sour magnesium is dry, is chromatographed by column and obtains target compound, and filler material is silica gel, and eluant, eluent is petroleum ether separation yield 90%.
Embodiment 2
1- (4- aminomethyl phenyl) -3- azido -4,4, the preparation (compound 2) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
4- (4- aminomethyl phenyl) -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, by method similarly to Example 1 into
Row obtains target compound separation yield 69%.
Embodiment 3
1- (4- isopropyl phenyl) -3- azido -4,4, the preparation (compound 3) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
4- (4- isopropyl phenyl) -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, by method similarly to Example 1 into
Row obtains target compound separation yield 77%.
Embodiment 4
1- (4- methoxyphenyl) -3- azido -4,4, the preparation (compound 4) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
4- (4- methoxyphenyl) -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, by method similarly to Example 1 into
Row obtains target compound separation yield 82%.
Embodiment 5
1- (3- chlorphenyl) -3- azido -4,4, the preparation (compound 5) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
4- (3- chlorphenyl) -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, carried out by method similarly to Example 1,
Obtain target compound separation yield 75%.
Embodiment 6
1- (2- chlorphenyl) -3- azido -4,4, the preparation (compound 6) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
4- (2- chlorphenyl) -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, carried out by method similarly to Example 1,
Obtain target compound separation yield 91%.
Embodiment 7
1- (4- chlorphenyl) -3- azido -4,4, the preparation (compound 7) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
4- (4- chlorphenyl) -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, carried out by method similarly to Example 1,
Obtain target compound separation yield 87%.
Embodiment 8
1- (4- fluorophenyl) -3- azido -4,4, the preparation (compound 8) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
4- (4- fluorophenyl) -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, carried out by method similarly to Example 1,
Obtain target compound separation yield 81%.
Embodiment 9
1- (4- bromophenyl) -3- azido -4,4, the preparation (compound 9) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
4- (4- bromophenyl) -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, carried out by method similarly to Example 1,
Obtain target compound separation yield 85%.
Embodiment 10
1- (3- trifluoromethyl) -3- azido -4,4, the preparation (compound 10) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
4- (3- trifluoromethyl) -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, by method similarly to Example 1
It carries out, obtains target compound separation yield 78%.
Embodiment 11
1- (the fluoro- 3- chlorphenyl of 2-) -3- azido -4,4, the preparation (compound 11) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
4- (the fluoro- 3- chlorphenyl of 2-) -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, by method similarly to Example 1
It carries out, obtains target compound separation yield 80%.
Embodiment 12
1- (the fluoro- 2- chlorphenyl of 4-) -3- azido -4,4, the preparation (compound 12) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
4- (the fluoro- 2- chlorphenyl of 4-) -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, by method similarly to Example 1
It carries out, obtains target compound separation yield 90%.
Embodiment 13
1- (4- carbethoxyphenyl) -3- azido -4,4, the preparation (compound 13) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
4- (4- carbethoxyphenyl) -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, by method similarly to Example 1 into
Row obtains target compound separation yield 48%.
Embodiment 14
1- (4- cyano-phenyl) -3- azido -4,4, the preparation (compound 14) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
4- (4- cyano-phenyl) -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, by method similarly to Example 1 into
Row obtains target compound separation yield 23%.
Embodiment 15
1-4 '-diphenyl -3- azido -4,4, the preparation (compound 15) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
1-4 '-diphenyl -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, carry out, obtain by method similarly to Example 1
Obtain target compound separation yield 87%.
Embodiment 16
1- (1- naphthalene) -3- azido -4,4, the preparation (compound 16) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
1- (1- naphthalene) -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, carry out, obtain by method similarly to Example 1
Obtain target compound separation yield 90%.
Embodiment 17
1- (3,4,5- trimethoxyphenyl) -3- azido -4,4, the preparation (compound 17) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
1- (3,4,5- trimethoxyphenyl) -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, by similarly to Example 1
Method carries out, and obtains target compound separation yield 95%.
Embodiment 18
1- (2- furyl) -3- azido -4,4, the preparation (compound 18) of the fluoro- 1- butylene of 4- tri-
In addition to by 4- phenyl -2- trifluoromethanesulfonate -1,1 in embodiment 1, the fluoro- 2- butylene of 1- tri- changes same mole into
1- (2- furyl) -2- trifluoromethanesulfonate -1,1, outside the fluoro- 2- butylene of 1- tri-, carried out by method similarly to Example 1,
Obtain target compound separation yield 48%.
Embodiment 19
1- phenyl -3- azido -4,4, the preparation (compound 1) of the fluoro- 1- butylene of 4- tri-
Other than change the dry ethylene glycol dimethyl ether in embodiment 1 into anhydrous tetrahydro furan, by similarly to Example 1
Method carries out, and obtains target compound proton magnetic yield 58% (using terephthalic acid (TPA) methyl esters as internal standard).
Embodiment 20
1- phenyl -3- azido -4,4, the preparation (compound 1) of the fluoro- 1- butylene of 4- tri-
Other than changing the dry ethylene glycol dimethyl ether in embodiment 1 into dry toluene, by method similarly to Example 1
It carries out, obtains target compound proton magnetic yield 54% (using terephthalic acid (TPA) methyl esters as internal standard).
Embodiment 21
1- phenyl -3- azido -4,4, the preparation (compound 1) of the fluoro- 1- butylene of 4- tri-
Other than changing the additive saleratus in embodiment 1 into sodium bicarbonate, by method similarly to Example 1 into
Row obtains target compound proton magnetic yield 84% (using terephthalic acid (TPA) methyl esters as internal standard).
Embodiment 22
1- phenyl -3- azido -4,4, the preparation (compound 1) of the fluoro- 1- butylene of 4- tri-
Other than changing the additive saleratus in embodiment 1 into potassium fluoride, by method similarly to Example 1 into
Row obtains target compound proton magnetic yield 86% (using terephthalic acid (TPA) methyl esters as internal standard).
Embodiment 23
1- phenyl -3- azido -4,4, the preparation (compound 1) of the fluoro- 1- butylene of 4- tri-
Other than the trimethyl silicane nitrine amount in embodiment 1 is reduced to 1 times of mole, by method similarly to Example 1
It carries out, obtains target compound proton magnetic yield 56% (using terephthalic acid (TPA) methyl esters as internal standard).
Embodiment 24
1- phenyl -3- azido -4,4, the preparation (compound 1) of the fluoro- 1- butylene of 4- tri-
Other than the trimethyl silicane nitrine amount in embodiment 1 is upgraded to 3 times of moles, by method similarly to Example 1
It carries out, obtains target compound proton magnetic yield 91% (using terephthalic acid (TPA) methyl esters as internal standard).
Embodiment 25
1- phenyl -3- azido -4,4, the preparation (compound 1) of the fluoro- 1- butylene of 4- tri-
Other than will be for 10mol% by the amount of the catalyst of triethylamine in embodiment 1, by method similarly to Example 1
It carries out, obtains target compound proton magnetic yield 71% (using terephthalic acid (TPA) methyl esters as internal standard).
Embodiment 26
1- phenyl -3- azido -4,4, the preparation (compound 1) of the fluoro- 1- butylene of 4- tri-
Other than the amount of the catalyst of triethylamine in embodiment 1 is changed to 20mol%, by method similarly to Example 1
It carries out, obtains target compound proton magnetic yield 83% (using terephthalic acid (TPA) methyl esters as internal standard).
Embodiment 27
1- phenyl -3- azido -4,4, the preparation (compound 1) of the fluoro- 1- butylene of 4- tri-
It other than it will be 25 DEG C by the reaction temperature in embodiment 1, be carried out by method similarly to Example 1, obtains mesh
It marks compound proton magnetic yield 25% (using terephthalic acid (TPA) methyl esters as internal standard).
Embodiment 28
1- phenyl -3- azido -4,4, the preparation (compound 1) of the fluoro- 1- butylene of 4- tri-
Other than the amount of the catalyst of triethylamine in embodiment 1 is changed to 5mol%, by method similarly to Example 1 into
Row obtains target compound proton magnetic yield 60% (using terephthalic acid (TPA) methyl esters as internal standard).
Embodiment 29
1- phenyl -3- azido -4,4, the preparation (compound 1) of the fluoro- 1- butylene of 4- tri-
Other than the amount of the catalyst of triethylamine in embodiment 1 is changed to 30mol%, by method similarly to Example 1
It carries out, obtains target compound proton magnetic yield 80% (using terephthalic acid (TPA) methyl esters as internal standard).
Embodiment 30
1- phenyl -3- azido -4,4, the preparation (compound 1) of the fluoro- 1- butylene of 4- tri-
Other than the trimethyl silicane nitrine amount in embodiment 1 is upgraded to 5 times of moles, by method similarly to Example 1
It carries out, obtains target compound proton magnetic yield 89% (using terephthalic acid (TPA) methyl esters as internal standard).
Embodiment 31
1- phenyl -3- azido -4,4, the preparation (compound 1) of the fluoro- 1- butylene of 4- tri-
Other than the amount of the saleratus in embodiment 1 is upgraded to 3 times of moles, by method similarly to Example 1 into
Row obtains target compound proton magnetic yield 80% (using terephthalic acid (TPA) methyl esters as internal standard).
Application Example 32
The synthesis of 1- phenyl -3- [1- (4- phenyl -1.2.3- triazol radical)] -4,4,4- tri- fluoro- 1- butylene
In Schlenk bottles of 25mL, under argon gas protection, 1- phenyl -3- azido -4,4, the fluoro- 1- butylene of 4- tri- are sequentially added
113.6mg (0.5mmol), acetonitrile 5mL, phenylacetylene 61.3mg (66uL, 0.6mmol), n,N-diisopropylethylamine 193.9mg
After (0.26mL, 1.5mmol), under 25 DEG C of stirrings, it is slowly added to cuprous iodide 190.5mg (1.0mmol).25 DEG C of stirring 12h,
After TLC detection has been reacted, saturated ammonium chloride solution is added and is quenched, ethyl acetate extraction, saturated common salt water washing, anhydrous magnesium sulfate
Dry, silica gel post separation, eluant, eluent is petroleum ether: ethyl acetate (volume ratio 95:5), obtains 1- phenyl -3- [1- (4- phenyl -
1.2.3- triazol radical)] -4,4,4- tri- fluoro- 1- butylene 72mg, yield: 44%.
White solid, fusing point: 166.5-166.7 DEG C of1H-NMR(CDCl3, 400Hz) and δ 8.00 (s, 1H), 7.88 (d, J=
6.9Hz, 2H), 7.45-7.36 (m, 8H), 6.84 (d, J=15.7Hz, 1H), 6.53 (dd, J=15.7,7.7Hz, 1H),
5.97-5.93 (m, 1H).
Application Example 33
1- phenyl -3- amino -4,4, the synthesis of the fluoro- 1- butylene of 4- tri-
In Schlenk bottles of 25mL, under argon gas protection, 1- phenyl -3- azido -4,4, the fluoro- 1- butylene of 4- tri- are sequentially added
113.6mg (0.5mmol), tetrahydrofuran 3mL, deionized water 45mg (2.5mmol), triphenylphosphine 0.2g (0.75mmol).?
Potassium hydroxide tune PH is added extremely in 25 DEG C of stirring 12h, concentration of reaction solution, ethyl acetate dilution, 1mol/L salt acid elution 3 times, water phase
12, methylene chloride extraction, anhydrous sodium sulfate is dry, and silica gel post separation, eluant, eluent is methylene chloride, obtains 1- phenyl -3- amino -
4,4,4- tri- fluoro- 1- butylene 68mg, yield: 68%.
Colourless liquid,1H-NMR(CDCl3, 400Hz) and δ 7.45-7.28 (m, 5H), 6.83 (d, J=15.9Hz, 1H), 6.20
(dd, J=15.9,6.4Hz, 1H), 4.04-3.97 (m, 1H), 1.62 (s, 2H).
Application Example 34
4- phenyl -2- amino -1,1, the synthesis of 1- trifluorobutane
In Schlenk bottles of 25mL, under argon gas protection, 1- phenyl -3- azido -4,4, the fluoro- 1- butylene of 4- tri- are sequentially added
113.6mg (0.5mmol), methanol 2mL, 10%Pd/C 11.4mg.After mixing evenly, it is passed through hydrogen, after GC detection has been reacted,
It filters (diatomite drainage), is spin-dried for solvent, obtain 4- phenyl -2- amino -1,1,1- trifluorobutane 87mg, yield: 86%.
Colourless liquid,1H-NMR(CDCl3, 400Hz) and δ 7.33-7.29 (m, 2H), 7.23-7.21 (m, 3H), 3.15-3.06
(m, 1H), 2.96-2.89 (m, 1H), 2.79-2.71 (m, 1H), 2.09-2.01 (m, 1H), 1.75-1.65 (m, 1H), 1.48
(s, 2H).
Claims (4)
1. a kind of prepare 1- aryl -3- azido -4,4, the method for the fluoro- 1- butene compounds of 4- tri-, the 1- aryl -3- nitrine
Base -4,4, the structure of the fluoro- 1- butene compounds of 4- tri- is as shown in Ι, it is characterised in that: is with compound II and trimethyl silicane nitrine
Raw material is reacted in the presence of catalyst and additive by following reaction equations, and compound shown in general formula I is obtained,
Wherein,
Ar is selected fromWherein X is derived from O, S, N (CH3)；N=1,2,
3,4,5, it is link position at wave；
R be selected from H, C1~C6 alkyl, phenyl, halogen, trifluoromethyl, trifluoromethoxy, C1~C4 alkoxy, C2~C5 ester group,
Cyano；
The catalyst is triethylamine；
The additive is one of sodium bicarbonate, saleratus, potassium fluoride；
The amount of the substance of the catalyst is 0.05~0.3 times of the amount of combinations of materials shown in general formula II；
The amount of the substance of the additive is 1.2~3 times of the amount of combinations of materials shown in general formula II；
The amount of the substance of the trimethyl silicane nitrine is 1~5 times of the amount of combinations of materials shown in general formula II；
The reaction carries out in a solvent, and the solvent is one of glycol dimethyl ether, tetrahydrofuran, toluene；
The reaction carries out in a solvent, and the ratio between amount of compound shown in general formula II and solvent is 1mmol:(5~15) mL；
The reaction temperature of the reaction is 25 DEG C~65 DEG C, and the reaction time is 6h~48h.
2. according to the method described in claim 1, it is characterized by: the R is H, methyl, isopropyl, phenyl, halogen, trifluoro
One of methyl, methoxyl group, ethoxycarbonyl or cyano.
3. according to the method described in claim 1, it is characterized by: the halogen is one of fluorine, chlorine, bromine, iodine.
4. according to the method described in claim 1, it is characterized by: the reaction time is 6h~for 24 hours.
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