CN1027539C - Trifluoride isopropenyl zinc reagent and its derivatives, preparation and application - Google Patents

Trifluoride isopropenyl zinc reagent and its derivatives, preparation and application Download PDF

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CN1027539C
CN1027539C CN 90106105 CN90106105A CN1027539C CN 1027539 C CN1027539 C CN 1027539C CN 90106105 CN90106105 CN 90106105 CN 90106105 A CN90106105 A CN 90106105A CN 1027539 C CN1027539 C CN 1027539C
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fluorine
derivative
pseudoallyl
zincon
reaction
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CN1051911A (en
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姜标
徐元耀
金富强
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Shanghai Institute of Organic Chemistry of CAS
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

The present invention provides a metallized building block reagent comprising fluorine, more specifically a trifluoro isopropenyl zinc reagent and a derivate thereof or the complex compound of the trifluoro isopropenyl zinc reagent, the derivate thereof and organic ligands comprising nitrogen. The trifluoro isopropenyl zinc reagent can be conveniently obtained by trifluoro isopropenyl halogen and a derivate thereof in polar solvents under the existence of zinc with high yield; organic ligands comprising nitrogen are added in reaction, and corresponding complex compounds can be obtained. The building block reagent comprising fluorine can generate cross-coupling reaction with aryl halide and alkenyl halogen under the existence of organic transition metal catalysts and under the mild condition for preparing styrene compounds comprising perfluoroalkyl substitution and 1, 3-conjugated diene compounds.

Description

Trifluoride isopropenyl zinc reagent and its derivatives, preparation and application
The present invention relates to a kind of preparation method of organic synthesis reagent, specifically provide a kind of metallized fluoro-building block, the preparation method of promptly fluorine-containing pseudoallyl zincon and derivative thereof.
Fluorinated organic compound causes people's extensive attention day by day playing effect of crucial importance aspect medicine, agricultural and the Industrial materials.Studying fluorine-containing organic building block, so that location and Stereoselective import fluorine-containing organic group in organic molecule, is that of studying of modern organic fluorine chemistry enlivens the field.Fluorine-containing organic building block generally is to utilize the industrial organofluorine compound that is easy to get to come synthetic.Trifluoro propene is the organofluorine compound of suitability for industrialized production.In recent years, and State University of New York [Chemical Review, 88,1011(1988)] the applied metal catalysis hydroformylation reaction, trifluoro propene is transformed into multiple fluorochemicals.But this method needs special reaction unit, be difficult to suitability for industrialized production, trifluoro propene is through bromination and potassium hydroxide dehydrobromination, can make 2-bromo-trifluoro propene (BTFP) (J.Am.Chem.Soc., 73,1042 easily, 1951), be a kind of starting raw material of very promising synthetic fluorinated organic compound, still few (Synthetic Organic Chemistry can will 786,1984 to its research at present; 775,1984), so synthetic and its application of fluorine-containing organic building block is the field of people's broad research.
The purpose of this invention is to provide a kind of metallized fluoro-building block, the preparation method of the complex compound of specifically a kind of fluorine-containing pseudoallyl zincon and derivative thereof or they and nitrogenous ligand.
Fluorine-containing pseudoallyl zincon and derivative thereof among the present invention have following molecular formula:
Figure 901061050_IMG3
(1), R wherein 1Or R 2Be respectively H, C 1-C 8Alkyl or aryl, Rf is C 1-C 8Perfluoroalkyl, X be Cl, Br or I.As trifluoro pseudoallyl zinc bromide (TFPZ), trifluoro pseudoallyl zinc iodide, trifluoro pseudoallyl chlorination zinc, 1-trifluoromethyl-2-phenyl-vinyl bromination zinc, 1-perfluoro propyl-vinyl bromination zinc, 1-perfluoro capryl-vinyl bromination zinc etc.
The complex compound of fluorine-containing pseudoallyl zincon and derivative and fluorine-containing ligand is fluorine-containing pseudoallyl zincon and derivative thereof and the complex compound that contains the organic compound ligand of a fluorine atom at least among the present invention.Described complex compound may form with following molecular formula and exist.
Figure 901061050_IMG4
Described nitrogenous organic ligand contains one or more nitrogen-atoms at least, should have two lone pair electrons can be coordinated on the zinc atom of fluorine-containing pseudoallyl zincon and derivative thereof on the nitrogen-atoms.Can be by nitrogen-atoms or be coordinated in zinc atom separately in two molecular complexs with two nitrogen-atoms in the molecular complex.Described nitrogenous organic ligand is tertiary amine preferably, and as Trimethylamine 99, triethylamine, Tributylamine etc., bipyridine or ethylenediamines compound are as Tetramethyl Ethylene Diamine, tetraethylethylenediamine etc.This complex compound can stably be present in the solvent, has good thermostability, places under several months or 80 ℃ of backflows in room temperature and can not decompose, and reactive behavior is constant.The complex compound of wherein fluorine-containing pseudoallyl zinc bromide and Tetramethyl Ethylene Diamine 19F nmr chemical displacement δ-16ppm is (with CF 2CO 2H is an external standard, and low for negative).
Among the present invention be with molecular formula
Figure 901061050_IMG5
(4), fluorine-containing different propylene halogen reaches
Its derivative is a raw material, with Zn(M) method of the neat above-mentioned fluorine-containing pseudoallyl zincon of (5) prepared in reaction of zinc and derivative 1 thereof.R wherein 1Or R 2Be H, C 1-C 8Alkyl or aryl, Rf is C 1-C 8Perfluoroalkyl, X is Cl, Br or I.M is Ag, Cu or Hg.
Method of the present invention can be carried out in polar solvent, and described polar solvent can be tetrahydrofuran (THF) (THF), glycol dimethyl ether, and ether, glycol dimethyl ether (DME) etc., the following institute of reaction formula formula:
Figure 901061050_IMG6
In preparation method of the present invention, compound 4 and 5 mole ratio can be 1: 0.5-5, recommending mole ratio is 1: 1-2.
In preparation method of the present invention, if add nitrogenous organic compound ligand 6, can make corresponding complex compound 2 or 3, described organic compound ligand is the organic compound that contains a nitrogen-atoms at least, on the nitrogen-atoms lone-pair electron should be arranged, and can be coordinated on the zinc atom of fluorine-containing pseudoallyl zincon and derivative thereof, as tertiary amine, Trimethylamine 99, triethylamine etc., the ethylenediamines compound is as Tetramethyl Ethylene Diamine, tetraethylethylenediamine etc. or bipyridine.The compound mole ratio can be 4: 5: 6=1: 0.5-5: 0.5-5, optimal molar ratio are 1: 1-2: 0.8-3.
Purpose of the present invention specifically provides a kind of fluorine-containing pseudoallyl zincon and derivative 1 thereof, or their complex compound 2 or 3 purposes.
In the production method of fluorine-containing sec.-propyl zincon of the present invention and derivative or their complex compound, the temperature of reaction of employing generally is a room temperature to 100 ℃, and optimal reaction temperature is 40-80 ℃.Reaction times is 1-48 hour, and the recommendation response time is 4-24 hour.Further increase temperature of reaction and reaction times, also help reaction yield and transformation efficiency.
In aforesaid method of the present invention, used Zn(M) zinc is neat will help the carrying out that react with the activator activation earlier, and described activator can be iodoethane or trimethylammonium chlorinated silane.As activating zinc-silver agent etc. with the trimethylammonium chlorinated silane.Activator level is Zn(M) 1/40-1/5 of gram molecular weight.
With compound of the present invention, 1 or complex compound 2 and 3, in the presence of transition-metal catalyst with aryl halide and thiazolinyl halogen 7 linked reactions take place, can synthesize the unsaturated hydrocarbon compound 8 that perfluoroalkyl replaces, be shown below:
Figure 901061050_IMG7
In the described alkylene halogen, R 3Can be allylic alkylation, cycloalkenyl group, aryl, heterocycloalkenyl and their derivative thereof, allylic alkylation can be allylic alkylation, steroidal thiazolinyl, aromatic base can be to contain phenyl ring, naphthalene nucleus, fluorenes ring, anthracene nucleus etc., heterocycloalkenyl contains the ring of S, an O or N at least, as contains pyridine, furans, imidazoles, azepine indenes, thiazole, indoles, carbazole, uracil nucleosides etc.X is Cl, Br or I.
Described transition-metal catalyst 9 is organic transition metal catalyzer, as the compound of organic palladium or nickel.The compound of organic palladium can be that organic nickel compounds such as four (triphenylphosphine) look, two (triphenylphosphine) palladium chloride, two (triphenylphosphine) palladium can be four (triphenylphosphine) nickel, two (triphenylphosphine) Nickel Chloride etc.
Fluorine-containing pseudoallyl zincon of the present invention and derivative preparation method thereof be simple, be convenient to preserve.Cross-coupling reaction takes place in energy and aryl halide smoothly under palladium or nickel catalysis, produce high yield, single α-trifluoromethyl styrene compound.As trifluoromethyl sec.-propyl bromination zinc (TFPZ) and iodobenzene in THF, make catalyzer with 0.02 molar tetrakis triphenylphosphine palladium, 45 ℃ were reacted 6 hours, produced α-trifluoromethyl styrene of 96%, employing to or position replace the nitro iodobenzene time, yield is good.Palladium catalysis of aryl bromide hydrocarbon and TFPZ reaction, the reaction times is slightly long.Adopting 2-bromine 6-methoxynaphthalene is that raw material can high yield obtains 2-(1-trifluoromethyl-vinyl)-6-methoxyl group-naphthalene, product is through hydroboration, and the oxidizing reaction that continues can conveniently make anti-inflammatory drug Naproxen Base (Naproxen) trifluoro substitutive derivative.
Compound 1 of the present invention and thiazolinyl halogen stereospecificity under palladium or nickel catalysis synthesizes 1 of trifluoromethyl, the 3-conjugated diene compound, as TFPZ and (E)-Beta-bromo vinylbenzene or (Z)-Beta-bromo vinylbenzene is raw material, obtain three-dimensional single-minded E or Z-1,3-diene coupled product, productive rate is respectively 87% and 91%.Similarly (E)-1 iodine hexene and TFPZ react singlely (3E)-2-Trifluoromethyl-1 .3-octadiene, and the conjugated dienes product that TFPZ and the reaction of 3-bromo-cyclonene then obtain is the very useful synthetic fluorine-containing monoterpene or the starting raw material of sesquiterpene.In fact, the product that obtains with TFPZ and thiazolinyl halogen linked reaction is a 1.3-diene that contains the isoprene structural unit of three fluorine atoms replacements, contain the synthetic of trifluoromethyl 1.3-conjugated diolefine, will provide effective ways for the active fluorine-containing material of synthesis of natural.3 beta-hydroxyl-17s-iodo-△ 5(6), 16(17)-the diene gonane can obtain 90% respective compound, introduce C easily on the steroidal side chain 20-trifluoromethyl.Also can make the uracil nucleoside derivates that α-trifluoromethyl vinyl substituted is arranged on the 5-position, 5-(1-trifluoromethyl-vinyl with present method)-3 ', 5 '-dibenzoyl-α '-deoxidation uracil nucleosides.Can make (1E)-(3-trifluoromethyl)-1,3-butadiene ylboronic acid diisopropyl ester with TFPZ with the reaction of (E)-(2-bromo vinyl) boric acid diisopropyl ester, the latter can synthesize a series of products again as borane reagent.
Fluorine-containing pseudoallyl zincon of the present invention and derivative thereof are that individual trifluoromethyl of great use is for thiazolinyl building block, its synthetic convenience, productive rate height.During application, reaction temperature and, simple to operate, be a kind of application prospect fluorine-containing reagent widely.
Following embodiment will further help to understand the present invention:
Embodiment 1
Among the embodiment 1HNMR Varian EM-360L type and Varian-200 type nmr determination: with CDCl 3Be solvent, TMS is interior mark, and δ is ppm, 19F NMR Varian EM-360L type nmr determination, CDCl 3Be solvent, CF 3COOH is external standard (δ .0.00), and low is negative value, and IR uses JMS-OIU type mass spectrograph to measure with Shimadzu IR-440 type determination of infrared spectroscopy, MS.
Reflux condensing tube is being housed, put into Zn(Ag in the there-necked flask of thermometer and dropping funnel) 49 grams, 360 milliliters of tetrahydrofuran (THF)s add 76 milliliters of Tetramethyl Ethylene Diamines under stirring, and drip the BTFP87.5 gram, finish, heating makes temperature of reaction about 60 ℃, reacts 9 hours, promptly makes trifluoride isopropenyl zinc reagent 10, productive rate is greater than 90% 19F NMR, δ .-16.0(s).
Embodiment 2
Roughly the same embodiment 1 condition prepares fluorine-containing pseudoallyl zincon derivative complex compound such as table 1.(table 1 is seen the literary composition back)
Product 11,12,13 and 14 wherein 19FNMR δ is respectively-16; + 4.4(3F, CF 3) ,+40(2F, CF 2, α) ,+45.5(10F, (CF 2) 5) ,+49.8(2F, CF 2ω) :+7(3F, CF 3) ,+40(2F, CF 2α) ,+45(2F, CF 2β) with-16.
Embodiment 3
CF 2C(Br)=CH 2With Zn(Ag)/reaction of TMEDA, corresponding mole ratio is 1: 1.5: the result of preparation 10 during 0.5-1, productive rate and transformation efficiency foundation 19FNMR records, and is interior mark with phenylfluoroform.(seeing Table 2)
Embodiment 4
The palladium catalyzed coupling reaction of fluorine-containing pseudoallyl zincon and aryl halide
In three-necked bottle, put into aryl halide 10 millimoles, (Ph 3P) 2Pd0.2 millimole and press the THF solution 20ml of the trifluoro-propenyl zincon of embodiment 1 method preparation contains reagent 20 millimoles, at a certain temperature reaction approximately.Thin-layer chromatography is followed the tracks of reaction.Reaction is finished, purification process, and after the removal of solvent under reduced pressure, thick product is with underpressure distillation or flash chromatography purifying, and the result is as shown in table 3.(seeing Table 3)
The analytical data of product is as follows in the table:
α-trifluoromethyl-vinylbenzene 15
IR V.1580，1500，1380cm -1
1H NMR δ.5.72（S，1H），5.92（S，1H），7.42（S.5H）
19F NMR δ.-11.0（S）
MS m/e172（M +）
C 9H 7F 3Calculated value C, 62.79 H, 4.10 F, 33.11
172.2 measured value C, 62.77 H, 425 F, 33.18
4-nitro-α-trifluoromethyl-vinylbenzene 16
IR V.1600，1540，1500，1358cm -1
1H NMR δ .5.90(S, 1H), 6.20(S, 1H), 7.12-7.60, the center is 7.39(A2X2,4H, J=4Hz)
19F NMR δ.-12.0（S）
MS m/e217（M +），198（M +-F），171（M +-NO 2）
C 9H 6FNO 2Calculated value C, 49.78 H, 2.79 N, 6.45 F, 26.25
217.2 measured value C, 49.98 H, 2.71 N, 6.41 F, 26.57
3-nitro-α-trifluoromethyl-vinylbenzene 17
IR V.1620，1580，1540，1500，1358cm -1
1H NMR δ.5.92（S，1H），6.15（S，1H），7.1-7.80（m，3H）8.34（S，1H）
19F NMR δ.-11.0（S）
MS m/e217（M +），171（M +-NO 2）
C 9H 6F 3NO 2Calculated value C, 49.78 H, 2.79 N, 6.45 F, 26.35
217.2 measured value C, 49.98 H, 2.51 N, 6.41 F, 26.30
4-bromo-α-trifluoromethyl-vinylbenzene 18
IR V.1600，1500，1359cm -1
1H NMR δ .5.73(S, 1H), 5.95(S, 1H), 7.10-7.58, the center is 7.36(A2X2,4H, J=4Hz)
19F NMR δ.-12.0（S）
MS m/e252（M +）
C 9H 6BrF 3Calculated value C, 43.06 H, 2.41 F, 22.70
251.2 measured value C, 43.41 H, 2.31 F, 22.79
4-ethanoyl-α-trifluoromethyl-vinylbenzene 19
IR V.1720，1600，1500，1358cm -1
1H NMR δ .2.10(S, 1H), 5.72(S, 1H), 6.00(S, 1H), 7.12-7.60, the center is 7.37(A2X2,4H, J=4Hz)
19F NMR δ.-11.0（S）
MS m/e214（M +）
C 11H 9F 3O calculated value C, 61.60 H, 4.23 F, 26.61
214.2 measured value C, 61.67 H, 4.60 F, 26.83
2,4-dinitrobenzene-α-trifluoromethyl-vinylbenzene 20
IR V.1610，1550，1540，1510，1358cm -1
1 H
NMR δ.5.78（S，1H），6.20（S，1H），7.70（d，1H，J＝4.0Hz），8.58（dd，1H，J＝4.0Hz，1.5Hz）8.90（d，1H，J＝1.5Hz）
19F NMR δ.-11.0（S）
MS m/e263（M ++1）
C 9H 5F 3N 2O 4Calculated value C, 41.24 H, 1.92 N, 10.69 F, 21.74
262.2 measured value C, 41.55 H, 1.77 N, 10.42 F, 21.79
2-nitro-α-trifluoromethyl-vinylbenzene 21
IR V.1610，1540，1500，1360cm -1
1H NMR δ.5.76（S，1H），6.21（S，1H），7.20～7.40（m，4H）
19F NMR δ.-11.8（S）
MS m/e217（M +）
C 9H 6NF 3O 2Calculated value C, 49.78 H, 2.79 N, 6.45 F, 26.25
217.2 measured value C, 49.89 H, 2.51 N, 6.90 F, 26.30
2-formyl radical-α-trifluoromethyl-vinylbenzene 22
IR V.1710，1610，1600，1500cm -1
1H NMR δ.5.54（S，1H），6.15（S，1H），7.20～7.80（m，4H）10.00（S，1H）
19F NMR δ.-10.00（S）
MS m/e201（M ++1），181（M +-F），151（M +-CHO）
C 10H 7F 3O calculated value C, 60.10 H, 3.53 F, 28.47
200.2 measured value C, 60.30 H, 3.30 F, 28.42
2-acetoxyl group-α-trifluoromethyl-vinylbenzene 23
IR V.1720，1610，1500，1358cm -1
1H NMR δ.2.00（S，3H），5.60（S，1H），6.18（S，1H）7.20～7.80（m，4H）
19F NMR δ.-12.0（S）
MS m/e230（M +）
C 11H 6F 3O 2Calculated value C, 57.40 H, 2.94 F, 24.76
230.2 measured value C, 57.31 H, 4.26 F, 24.57
1-(1-trifluoromethyl-vinyl)-naphthalene 24
IR V.1610，1580，1510，1358cm -1
1H NMR δ.5.83（S，1H），6.02（S，1H），7.45（m，7H）
19F NMR δ.-12.4（S）
MS m/e222（M +），153（M +-CF 2）
C 12H 9F 3Calculated value C, 70.27 H, 4.08 F, 25.05
Measured value C, 70.36 H, 4.16 F, 25.46
2-(1-trifluoromethyl-vinyl)-naphthalene 25
IR V.1610，1580，1510，1358cm -1
1H NMR δ.5.86（S，1H），6.04（S，1H），7.50（m，7H）
19F NMR δ，-12.6（S）
MS m/e222（M +）
C 12H 9F 3Calculated value C, 70.27 H, 4.08 F, 25.05
Measured value C, 70.11 H, 4.24 F, 25.33
2-(1-trifluoromethyl-vinyl)-1-methoxyl group-naphthalene 26
m.p.68-69℃
IR（KCl） V.1600，1580，1500，1358cm -1
1H NMR δ.3.90（S，3H），5.82（S，1H），6.01（S，1H），7.5（m，6H）
19F NMR δ.-13.0（S）
MS m/e252（M +），183（M +-CF 2），221（M +-CH 2O）
C 14H 11F 3O calculated value C, 66.66 H, 4.40 F, 22.60
252.2 measured value C, 66.42 H, 4.23 F, 22.42
Embodiment 5
11,12 or 13 compounds, under organic palladium or nickel catalyzator effect, as shown in table 4 with the halogeno-benzene reaction result in the glycol dinitrate ether solvents, all the other conditions are with embodiment 4
Wherein the analytical data of product is as follows:
α-trifluoromethyl-beta-phenyl vinylbenzene (27)
19F NMR δ.-10.0（3F，CF 3）
1H NMR（CDCl 3）δ.6.91（1H，S），7.5～7.8（m，10H）
MS m/e248（M +）
Ultimate analysis (calculated value) C, 72.60(72.57) H, 4.86(4.47) F, 22.59(22.96)
2-perfluoro propyl vinylbenzene (28)
19F NMR δ.+7（3F，CF 3）+42（2F，CF 2α），+45（2F，CF2β）
1H NMR（CDCl 3）δ.5.81（1H，S），6.20（1H，S），7.5（S，5H）
MS m/e272（M +），253（M-F）
Ultimate analysis (calculated value) C, 48.51(48.55) H, 2.36(2.59) F, 48.80(48.86)
2-perfluoro propyl vinylbenzene (29)
1F NMR δ.+4.4（3F，CF 3）+43（2F，CF 2α），+45.5（10F，（CF 2） 5），+50（2F，CF2ω）
1H NMR（CDCl 3）δ.5.83（S，1H），6.02（S，1H），7.4（S，5H）
MS m/e522（M +），523（M-F）
Ultimate analysis (calculated value) C, 36.76(36.80) H, 1.48(1.35) F, 61.55(61.85)
Embodiment 6
The palladium catalyzed coupling reaction of trifluoro pseudoallyl zinc bromide and thiazolinyl halogen the results are shown in Table 5, and condition sees Table 5 with embodiment 4()
(1E)-and 1-phenyl-3-Trifluoromethyl-1,3-divinyl (30)
IR V.1680，1600，1500，1358cm -1
1H
NMR δ.5.45（S，1H），5.70（S，1H），6.15（d，1H＝16Hz），6.87（α，1H，J＝16Hz），7.26（S，5H）
19F NMR δ.-8.00（S）
MS m/e198（M +），129（M +-CF 3）
C 11H 9F 3Calculated value C, 66.66 H, 4.58 F, 28.76
198.2 measured value C, 66.70 H, 4.64 F, 28.77
(IZ)-1-phenyl-3-Trifluoromethyl-1 .3-divinyl (31)
IR V.1640，1600，1580，1500，1324cm -1
1H
NMR δ.5.40（S，1H），5.68（S，1H），6.02（d，1H，J＝12Hz），6，75（d，1H，J＝12Hz），7.27（S，5H）
19F NMR δ.-8.0（S）
MS m/e198（M +），177（M +-F），129（M +-CF 3）
C 11H 9F 3Calculated value C, 66.66 H, 4.58 F, 28.76
198.2 measured value C, 66.53 H, 4.72 F, 29.05
2-phenyl-3-Trifluoromethyl-1 .3-divinyl (32)
IR V.1680，1600，1570，1500，1358cm -1
1H NMR δ.5.46（S，2H），5.52（S，1H），5.92（S，1H），7.31（S，5H）
19F NMR δ.-12.0（S）
MS m/e198（M +），177（M +-F），129（M +-CF 3）
C 11H 9F 3Calculated value C, 66.66 H, 4.58 F, 28.76
198.2 measured value is H C.66.59,4.64 F, 28.45
(2E)-2-methyl-4-trifluoromethyl-2.4-diene-methyl valerate (33)
IR V.1720，1640，1358cm -1
1H
NMR δ.2.04（d，3H，J＝1.6Hz），3.80（S，3H），5.63（S，1H），6.09（S，1H），7.09（S，1H）
19F NMR δ.-7.2（S）
MS m/e194（M +），163（M +-OCH 3），179（M +-CH 3）
C 8H 9F 3O 2Calculated value C, 49.48 H, 4.67 F, 29.35
194.2 measured value C, 49.54 H, 4.78 F, 29.67
(3E)-2-Trifluoromethyl-1 .3-octadiene (34)
IR V.1640，1340cm -1
1H
NMR δ.0.80（t，3H，J＝6Hz），1.03（m，4H），2.01（m，2H），5.30（1H，d，J＝16Hz），5.60（S，1H）5.90（S，1H），6.20（m，1H）
19F NMR δ.-12.0（S）
MS m/e166（M +）
C 9H 13F 3Calculated value C, 57.82 H, 7.88 F, 34.30
166.2 measured value C, 57.77 H, 7.85 F, 34.27
1-(1-trifluoromethyl-vinyl)-tetrahydrobenzene (35)
IR V.1640，1340cm -1
1H NMR δ.1.65（m，4H），2.17（m，4H），5.41（S，1H）5.60（S，1H），6.08（m，1H）
19F NMR δ.-12.0（S）
MS m/e176（M +），107（M +-CF 3）
C 9H 11F 3Calculated value C, 61.36 H, 6.29 F, 32.35
176.2 measured value C, 61.30 H, 6.44 F, 32.27
3-(1-trifluoromethyl-vinyl)-hexamethylene-2-ketenes (36)
IR V.1686，1605，1340cm -1
1H NMR δ.1.80～3.00（m，6H），5.69（S，1H），6.01（S，1H），6.34（S，1H）
19F NMR δ.-12.0（S）
MS m/e190（M +），162（M 2-CO）
C 9H 9F 3O calculated value C, 56.85 H, 4.77 F, 29.97
190.2 measured value C, 56.81 H, 4.89 F, 30.21
3 beta-hydroxies-△ 5(6), 16(17), 20(22)-21-three fluoro-23,24,25,26,27-five loses carbon-cholestane (37)
m.p. 134-135℃
IR（KCl） V.3400，1600～1620（br），1358cm -1
1H
NMR δ.0.90（S.3H，18-H），100（S，3H，19-H），3.50（m，3-H），5.30（m，1H，6-H），5.48（S，1H，22-H），5.60（S，22-H），5.92（m，1H，16-H）
19F NMR δ.-12.0（S）
MS m/e366（M +），351（M +-CH 2），333（M +-H 2O-CH 2）
C 22H 29F 3O calculated value C, 72.11 H, 7.98 F, 15.35
366.5 measured value C, 72.26 H, 8.22 F, 15.41
5-(1-trifluoromethyl-vinyl)-3 ', 5 '-dibenzoyl-2 '-deoxidation uracil nucleosides (38)
IR（KCl）V.1760，1720，1680，1500，1460，1358cm -1
1H
NMR（200MHz）δ.2.38-2.44（m，1H，2′-H），2.78（dd，1H，J＝7.5Hz，2′-H），4.62（m，1H，4′-H），4.74（d，2H，J＝5Hz，5′-H），5.66（d，1H，J＝6.6Hz，3′-H），5.98（S，1H，Vinyl-H），6.14（d，1H，J＝1.2Hz，Vinyl-H），6.42（dd，J＝5.3Hz，J＝8.2Hz，1′H），7.32-7.44（m，5H，Bz），7.85（S，1H，6-H），7.99（m，5H，Bz）
19F NMR δ.-10.6（S）
MS m/e530（M +），325（M +-
Figure 901061050_IMG8
）206（
Figure 901061050_IMG9
）
C 26H 21N 2F 3O 7Calculated value C, 58.87 H, 39.90 N, 5.28, F, 10.74
530.5 measured value C, 58.51 H, 40.01 N, 5.64, F.10.34
Embodiment 7
In the presence of transition-metal catalyst, the cinnamic reaction of compound 13 and Beta-bromo, condition is with embodiment 6, reaction times 10h, 60 ℃ of temperature of reaction obtain 1-phenyl 3-perfluoro propyl divinyl (1.3) (39), and molecular formula is C 6H 5, productive rate 94%.
The product analysis result:
19F NMR δ.+7（3F，CF 3），+43（2F，CF 2α），+45（2F，CF 2β）
1H
NMR δ.5.40（S，1H），5.80（S，1H），6.15（d，1H），J＝16Hz，1H），6.87（d，J＝16Hz，1H），7.26（S，5H）
Ultimate analysis (calculated value) C, 25.24(52.36) H, 3.35(3.04), F, 44.26(44.60)
Embodiment 8
The preparation of 6-methoxyl group-(α-trifluoromethyl)-2-naphthylacetic acid (40)
2-(1-trifluoromethyl-vinyl)-6-methoxyl group-naphthalene (26) (504 milligrams, 2 millimoles) is dissolved among 5 milliliters the DME, adds BH 2Me 2S(10M/L, 0.3ml, 3 millimoles), refluxing after 8 hours, room temperature is placed and is spent the night.Reaction flask is chilled to 0 ℃, adds NaOH(50%, 0.5 milliliter), ethanol (1 milliliter), and H 2O 2After (3%, 0.4 milliliter) reacted half an hour, the reaction solution ethyl acetate extraction was used saturated NaHCO 3, saturated NaCl washing, Na 2SO 4Dry.Concentrating under reduced pressure gained crude product is dissolved in acetone (15ml), under 0 ℃, drip Jones ' reagent of 1.5ml, react after 1 hour, add the Virahol of 1ml, removal of solvent under reduced pressure, after residuum extracted with diethyl ether, ether extraction liquid were washed with saturated NaCl, the NaOH with 1N extracted again, the alkali extracting solution of gained is carefully used 2NH under 0 ℃ 2SO 4Be neutralized to acidity, separate out solid, use ether extraction once more.Ether extracted liquid washs with saturated NaCl, Na 2SO 4Drying, removal of solvent under reduced pressure get product through a short flash chromatography column purification; Get 390 milligrams, productive rate 69%.27.6gCrO 3, add 23 milliliters of vitriol oils, be diluted with water to 100 milliliters.
The product analysis result
m.p.140～142℃
IR（ KCl）
V.3500，1720，1600，1500cm -1 1HNMR δ.3.93（S，3H），4.49（q，J＝8.5H，1H），7.5（m，6H），10.5（S，1H）
19F NMR δ.-3.0（d，J＝8.5Hz，）
MS m/e284（M +）
C 14H 11F 3O 3Calculated value C, 59.16 H, 3.90 F, 20.05
284.2 measured value C, 59.27 H, 4.29 F, 20.17
Embodiment 9
(1E)-(3-trifluoromethyl)-1,3-butadiene ylboronic acid diisopropyl ester (41) preparation
With 5.8 gram (E)-(2-bromo vinyl) boric acid diisopropyl ester and 40 milligrams of PdCl 2(pph 3) 2Tetrahydrofuran solution 50 millimoles that add the different propylene zinc bromide of trifluoro in the mixture then, with this reaction solution reflux 1 hour, are chilled to room temperature, remove and desolvate, and residuum normal hexane extraction, extracting solution be through concentrated and underpressure distillation, obtain molecular formula and are:
B(OPr-i) 241.38 the gram, productive rate 61%.
19F NMR(is solvent-free) δ .-10.0
1H
NMR δ.1.03（d，J＝6Hz，12H），4.35（m，J＝16Hz，2H），5.48（S，1H），5.62（S，1H），5.95（d，J＝1
Table 1
Compound 4 compounds 5 solvent complex agent 8 thermotonus time mole ratio product 2 or 3 productive rates
R 1R 3Rf X M ℃ h 4∶5∶6 q
H C 6H 5CF 3Br Cu DME bipyridine 80 20 112 11 89
H H C 8F 17I Hg THF TMEDA 70 10 1 0.8 1.2 12 70
H H C 3F 7Br Hg RHF Tributylamine 60 20 1: 4: 4 13 85
H H CF 3Cl Ag DME TMEDA 20 48 1∶1∶2 14 30
* the Zn(Ag in solvent), be used in the activation of methyl chlorinated silane earlier
The complex compound of the fluorine-containing pseudoallyl zincon of table 4 derivative and the reaction of halogeno-benzene
Figure 901061050_IMG12
Embodiment 3
CF 2C(Br)=CH 2With Zn(Ag)/reaction of TMEDA, corresponding mole ratio is 1: 1.5: the result of preparation 10 during 0.5-1, productive rate and transformation efficiency foundation 19F NMR records, and is interior mark with phenylfluoroform.
Table 2
Reaction conditions
H/ ℃ of productive rate % of TMEDA solvent transformation efficiency %
0.5 Et2O 24/40 50 50
1，0 Et2O 24/40 98 100
0.5 THF 9/60 47 50
1.0 THF 9/60 93 100
1.0 DME 9/67 90 100
1.0 DMF 3/40 30 100
Embodiment 4
The palladium catalyzed coupling reaction of fluorine-containing pseudoallyl zincon and aryl halide
In three-necked bottle, put into aryl halide 10 millimoles, (Ph 3P) 2Pd0.2 millimole and press the THF solution 20ml of the trifluoro-propenyl zincon of embodiment 1 method preparation contains reagent 20 millimoles, at a certain temperature reaction approximately.Thin-layer chromatography is followed the tracks of reaction.Reaction is finished, purification process, and after the removal of solvent under reduced pressure, thick product is with underpressure distillation or flash chromatography purifying, and the result is as shown in table 3.
Table 3 Pd(pph 2) 4The linked reaction of catalysis TFPZ and aryl halide (7)
Embodiment 6
The palladium catalyzed coupling reaction of trifluoro pseudoallyl zinc bromide and thiazolinyl halogen the results are shown in Table 5, and condition is with embodiment 4
Table 5 pd(pph 3) 4The linked reaction of TFPZ and thiazolinyl halogen under the catalysis
Figure 901061050_IMG14

Claims (7)

1, the preparation method of the complex compound of a kind of fluorine-containing pseudoallyl zincon and derivative thereof or they and nitrogenous ligand, wherein fluorine-containing pseudoallyl zincon and derivative thereof have
Molecular formula, wherein R 1Or R 3Be respectively H, C 1-C 8Alkyl or aryl, Rf is C 1-C 8Perfluoroalkyl, X be Cl, Br or I, described ligand is the organic compound that contains a nitrogen-atoms at least, as tertiary amine, benzidine, ethylenediamines compound, it is characterized in that and can be made by following method respectively:
(1) having molecular formula is
Figure 901061050_IMG2
Fluorine-containing different propylene halogen or derivative and Zn (M) reaction, both mole ratios are 1: 0.5-5;
(2) add the organic compound ligand that contains a nitrogen-atoms at least again in above-mentioned reaction, the mole ratio of fluorine-containing different propylene halogen or derivative, Zn (M) and organic compounds containing nitrogen ligand is 1: 0.5-5: 0.5-5.
2, the preparation method of the complex compound of a kind of fluorine-containing pseudoallyl zincon as claimed in claim 1 and derivative thereof or they and nitrogenous ligand, it is characterized in that adopting this method to synthesize the different propylene zinc halide of trifluoro, or they and contain the complex compound of the organic compound ligand of a nitrogen-atoms at least.
3, the preparation method of the complex compound of a kind of fluorine-containing pseudoallyl zincon as claimed in claim 1 and derivative thereof or they and nitrogenous ligand is characterized in that fluorine-containing different propylene halogen or derivative and Zn(M) reaction, both mole ratios are 1: 1-2.
4, the preparation method of the complex compound of a kind of fluorine-containing pseudoallyl zincon as claimed in claim 3 and derivative thereof or they and nitrogenous ligand, its feature is reacted in polar solvent.
5, the preparation method of the complex compound of a kind of fluorine-containing pseudoallyl zincon as claimed in claim 1 and derivative thereof or they and nitrogenous ligand, it is characterized in that fluorine-containing different propylene halogen or derivative, Zn(M) mole ratio with the organic compounds containing nitrogen ligand is 1: 1-2: 0.8-3.
6, the preparation method of fluorine-containing pseudoallyl zincon as claimed in claim 1 and derivative thereof or they and nitrogenous ligand complexe is characterized in that temperature of reaction is a room temperature to 100 ℃, and the reaction times is 1-48 hour.
7, the preparation method of the complex compound of fluorine-containing pseudoallyl zincon as claimed in claim 3 and derivative thereof or they and nitrogenous ligand, it is characterized in that Zn(M) activate with activator, described activator can be iodoethane, trimethylammonium silicon chlorides, and gram molecular weight is Zn(M) 1/40-1/5.
CN 90106105 1990-12-22 1990-12-22 Trifluoride isopropenyl zinc reagent and its derivatives, preparation and application Expired - Fee Related CN1027539C (en)

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