CN114773161B - (4E) -1-fluoro-2, 5-diaryl-4-pentene-2-ol derivative and synthetic method thereof - Google Patents
(4E) -1-fluoro-2, 5-diaryl-4-pentene-2-ol derivative and synthetic method thereof Download PDFInfo
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- 238000010189 synthetic method Methods 0.000 title description 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 52
- 238000000034 method Methods 0.000 claims abstract description 42
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 38
- 239000001301 oxygen Substances 0.000 claims abstract description 38
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 38
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- 239000003960 organic solvent Substances 0.000 claims abstract description 9
- 230000009471 action Effects 0.000 claims abstract description 3
- 239000012429 reaction media Substances 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 288
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 96
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 68
- 238000004440 column chromatography Methods 0.000 claims description 66
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical group [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 61
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims description 46
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 44
- 239000003208 petroleum Substances 0.000 claims description 34
- 230000002194 synthesizing effect Effects 0.000 claims description 34
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 32
- 239000012295 chemical reaction liquid Substances 0.000 claims description 32
- 239000003480 eluent Substances 0.000 claims description 32
- 238000002390 rotary evaporation Methods 0.000 claims description 32
- 239000002904 solvent Substances 0.000 claims description 32
- 238000001816 cooling Methods 0.000 claims description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- 150000001543 aryl boronic acids Chemical class 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 5
- 239000012046 mixed solvent Substances 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 3
- BIWQNIMLAISTBV-UHFFFAOYSA-N (4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1 BIWQNIMLAISTBV-UHFFFAOYSA-N 0.000 claims description 2
- MNJYZNVROSZZQC-UHFFFAOYSA-N (4-tert-butylphenyl)boronic acid Chemical compound CC(C)(C)C1=CC=C(B(O)O)C=C1 MNJYZNVROSZZQC-UHFFFAOYSA-N 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- 239000012044 organic layer Substances 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- ROEQGIFOWRQYHD-UHFFFAOYSA-N (2-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC=C1B(O)O ROEQGIFOWRQYHD-UHFFFAOYSA-N 0.000 claims 1
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 claims 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 abstract description 12
- 229910052731 fluorine Inorganic materials 0.000 abstract description 12
- 239000011737 fluorine Substances 0.000 abstract description 12
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 238000001308 synthesis method Methods 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 4
- 239000002253 acid Substances 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 239000000575 pesticide Substances 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 239000003513 alkali Substances 0.000 abstract description 2
- 238000006555 catalytic reaction Methods 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 125000000524 functional group Chemical group 0.000 abstract description 2
- 239000003446 ligand Substances 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 description 102
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 94
- 238000010438 heat treatment Methods 0.000 description 30
- 239000000203 mixture Substances 0.000 description 30
- 238000003756 stirring Methods 0.000 description 30
- -1 o-methylphenyl Chemical group 0.000 description 21
- 238000012512 characterization method Methods 0.000 description 16
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 4
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 150000001336 alkenes Chemical class 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 2
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- YVCYOVLYYZRNJC-UHFFFAOYSA-N (2-methoxyphenoxy)boronic acid Chemical compound COC1=CC=CC=C1OB(O)O YVCYOVLYYZRNJC-UHFFFAOYSA-N 0.000 description 1
- NSJVYHOPHZMZPN-UHFFFAOYSA-N (2-methylphenyl)boronic acid Chemical compound CC1=CC=CC=C1B(O)O NSJVYHOPHZMZPN-UHFFFAOYSA-N 0.000 description 1
- DJGHSJBYKIQHIK-UHFFFAOYSA-N (3,5-dimethylphenyl)boronic acid Chemical compound CC1=CC(C)=CC(B(O)O)=C1 DJGHSJBYKIQHIK-UHFFFAOYSA-N 0.000 description 1
- QBLFZIBJXUQVRF-UHFFFAOYSA-N (4-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Br)C=C1 QBLFZIBJXUQVRF-UHFFFAOYSA-N 0.000 description 1
- CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 1
- SXLHAMYMTUEALX-UHFFFAOYSA-N (4-methoxyphenoxy)boronic acid Chemical compound COC1=CC=C(OB(O)O)C=C1 SXLHAMYMTUEALX-UHFFFAOYSA-N 0.000 description 1
- XPEIJWZLPWNNOK-UHFFFAOYSA-N (4-phenylphenyl)boronic acid Chemical compound C1=CC(B(O)O)=CC=C1C1=CC=CC=C1 XPEIJWZLPWNNOK-UHFFFAOYSA-N 0.000 description 1
- 238000007341 Heck reaction Methods 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000806 fluorine-19 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C33/40—Halogenated unsaturated alcohols
- C07C33/46—Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic parts
- C07C33/48—Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic parts with unsaturation outside the aromatic rings
- C07C33/483—Monocyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/10—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C323/18—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
- C07C323/19—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton with singly-bound oxygen atoms bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention belongs to the technical field of fluorine-containing compound preparation, and discloses a (4E) -1-fluoro-2, 5-diaryl-4-pentene-2-alcohol derivative and a synthesis method thereof. The (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative is shown in a formula I. The method comprises the following steps: organic solvent is used as reaction medium, and 1-fluoro-2-aryl-4-pentene-2-alcohol derivative and arylboric acid react under the action of catalyst and oxygen to obtain (4E) -1-fluoro-2, 5-diaryl-4-pentene-2-alcohol derivative. The method is efficient, the conditions are simple and mild, the addition of ligand and alkali is not needed, and the target product can be obtained only by catalysis of catalyst/oxygen; the reaction has high adaptability to functional groups, wide adaptability to substrates and high product yield, and can be amplified to gram-scale production and synthesis, and the obtained product has wide application in the fields of pesticides, medicines and materials.
Description
Technical Field
The invention belongs to the field of fluorine-containing compounds, and particularly relates to a (4E) -1-fluoro-2, 5-diaryl-4-pentene-2-alcohol derivative and a synthesis method thereof.
Background
Fluorine element has large electronegativity and small radius, and fluorine atoms or fluorine-containing groups are introduced into organic molecules, so that the physicochemical properties of the organic molecules can be effectively changed, and the fluorine-containing compound has very wide application in the fields of biological medicine, pesticide, material science and the like. It was investigated that fluorine-containing compounds account for about 30% in all agrochemicals and about 20% in the pharmaceuticals. Fluorinated materials have been widely used in liquid crystal displays. In addition, fluorine-labeled molecular probes can also be used to diagnose diseases. Therefore, in order to meet the urgent needs of research and exploration of fluorine-containing compounds and the growing variety and amount of fluorine-containing compounds, efficient synthesis of fluorine-containing compounds is one of the problems that the chemists are urgent to solve.
The intermolecular cross-coupling reaction is one of the important methods for constructing C-C bonds, and Nobel chemistry in 2010 is obtainedThe Heck reaction of the prize is to construct C (sp 2 )-C(sp 2 ) A key. However, this method is generally limited to activated electron-deficient olefins, but it is difficult for non-activated olefins to undergo a coupling reaction. Thus, developing a process that efficiently achieves the reaction of an unactivated olefin with an aryl group is currently still a challenging topic of research.
Disclosure of Invention
In view of the above drawbacks and deficiencies of the prior art, a primary object of the present invention is to provide a process for the efficient synthesis of (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives.
It is another object of the present invention to provide a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives.
The aim of the invention is achieved by the following technical scheme.
A (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative having the structure:
wherein Ar is 1 Is phenyl, p-methylphenyl, o-methylphenyl, p-methoxyphenyl, o-methoxyphenyl, 3, 4-dimethoxyphenyl, p-fluorophenyl, o-fluorophenyl, p-chlorophenyl, o-chlorophenyl, 3, 5-dichlorophenyl, p-bromophenyl, o-bromophenyl or p-trifluoromethylphenyl.
Ar 2 Is phenyl, p-tolyl, o-tolyl, p-methoxyphenyl, o-methoxyphenyl, p-thiomethylphenyl (p-methylthiophenyl), p-tert-butylphenyl, p-fluorophenyl, m-fluorophenyl, p-chlorophenyl, p-bromophenyl, o-bromophenyl, 3, 5-dimethylphenyl, p-methylsulfonylphenyl, p-phenylphenyl or 2-naphthyl.
R 1 Is hydrogen, methyl or ethyl.
R 2 Is hydrogen or fluorine.
R 3 Is hydrogen, methyl or ethyl
R 4 Is hydrogen or methyl.
The synthesis method of the (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative comprises the following steps:
organic solvent is used as reaction medium, 1-fluoro-2-aryl-4-pentene-2-alcohol derivative and arylboric acid react under the action of catalyst and oxygen, and after the reaction, the product is separated and purified to obtain (4E) -1-fluoro-2, 5-diaryl-4-pentene-2-alcohol derivative.
The 1-fluoro-2-aryl-4-penten-2-ol derivative isWherein Ar is 1 Is phenyl, p-methylphenyl, o-methylphenyl, p-methoxyphenyl, o-methoxyphenyl, 3, 4-dimethoxyphenyl, p-fluorophenyl, o-fluorophenyl, p-chlorophenyl, o-chlorophenyl, 3, 5-dichlorophenyl, p-bromophenyl, o-bromophenyl or p-trifluoromethylphenyl.
The aryl boric acid is Ar 2 B(OH) 2 Wherein Ar is 2 Is phenyl, p-tolyl, o-tolyl, p-methoxyphenyl, o-methoxyphenyl, p-thiomethylphenyl (p-methylthiophenyl), p-tert-butylphenyl, p-fluorophenyl, m-fluorophenyl, p-chlorophenyl, p-bromophenyl, o-bromophenyl, 3, 5-dimethylphenyl, p-methylsulfonylphenyl, p-phenylphenyl or 2-naphthyl.
R 1 Is hydrogen, methyl or ethyl.
R 2 Is hydrogen or fluorine.
R 3 Is hydrogen, methyl or ethyl.
R 4 Is hydrogen or methyl.
The molar ratio of the 1-fluoro-2-aryl-4-penten-2-ol derivative to the arylboronic acid is 1:1-1:4, preferably 1: (2 to 4), more preferably 1 (2.5 to 3.5), still more preferably 1:3.
the catalyst is one or more of palladium acetate, palladium iodide and tetrakis (triphenylphosphine) palladium, and more preferably tetrakis (triphenylphosphine) palladium.
The molar ratio of the catalyst to the 1-fluoro-2-aryl-4-penten-2-ol derivative is 1: (5-100), preferably 1:20.
The organic solvent is more than one of N, N-dimethylformamide, dimethyl sulfoxide, toluene, nitromethane and tetrahydrofuran, preferably a mixed solvent of N, N-dimethylformamide and dimethyl sulfoxide;
the volume ratio of the N, N-dimethylformamide to the dimethyl sulfoxide is 1:1.
The reaction is carried out in an oxygen atmosphere, the reaction temperature is 40-110 ℃, and the reaction time is 3-16h. Preferably, the reaction temperature is 70 to 100 ℃, more preferably 80 to 95 ℃, and the reaction time is 10 to 16 hours.
The subsequent treatment is to cool to room temperature after the reaction is finished, add saline solution or water and organic solvent, extract the reaction liquid, decompress and evaporate the organic layer by rotary evaporation to remove the solvent to obtain crude product, and purify by column chromatography to obtain the (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative.
In the subsequent treatment, the organic solvent is ethyl acetate or dichloromethane.
The column chromatography purification refers to the purification by petroleum ether: the mixed solvent of ethyl acetate is used for column chromatography purification of eluent. Petroleum ether: volume ratio of ethyl acetate: (20-500): 1.
The reaction equation involved in the method of the invention:
compared with the prior art, the invention has the following advantages:
(1) The synthesis method is efficient, and raw materials used are easy to obtain; the reaction has good adaptability to functional groups, wide adaptability to substrates and high product yield;
(2) The synthesis method is efficient, the conditions are simple and mild, the addition of ligand and alkali is not needed, and the target product can be obtained only by catalysis of catalyst/oxygen;
(3) The synthesis method can be amplified to gram-scale production, is simple and safe to operate, has mild reaction conditions, and has good industrial application prospect;
(4) The product obtained by the invention has wide application in the fields of pesticides, medicines and materials.
Drawings
FIG. 1 shows the products obtained in examples 1 to 15 1 H NMR spectrum;
FIG. 2 shows the products obtained in examples 1 to 15 13 C NMR spectrum;
FIG. 3 shows the products obtained in examples 1 to 15 19 F NMR spectrum;
FIG. 4 is a single crystal structure diagram of the product obtained in example 25.
Detailed Description
The present invention will be described in further detail with reference to specific examples, but embodiments of the present invention are not limited thereto.
Example 1:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a reaction vessel, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of phenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the reaction vessel (oxygen was introduced), and the reaction system was stirred at 90℃for reaction for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate to remove a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 95%.
Example 2:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magnet, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of palladium acetate and 2 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for reaction for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline solution and ethyl acetate, extracting the reaction liquid, performing reduced pressure rotary evaporation on the ethyl acetate, removing the solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 46%.
Example 3:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline solution and ethyl acetate, extracting the reaction liquid, performing reduced pressure rotary evaporation on the ethyl acetate, removing the solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 77%.
Example 4:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magnet, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of palladium iodide and 2 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for reaction for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 23%.
Example 5:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of dimethyl sulfoxide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 79%.
Example 6:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of toluene were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 51%.
Example 7:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of nitromethane were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 50%.
Example 8:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 110℃for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 56%.
Example 9:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 70℃for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 74%.
Example 10:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 50℃for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 33%.
Example 11:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.3 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 70℃for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 15%.
Example 12:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 70℃for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 66%.
Example 13:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.8 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 70℃for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 64%.
Example 14:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 70℃for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 89%.
Example 15:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.04 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 70℃for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 54%.
The products obtained in examples 1 to 15 1 H NMR， 13 C NMR， 19 The F NMR charts are shown in fig. 1, 2 and 3, respectively, and the structural characterization data are as follows:
1 H NMR(400MHz,DMSO-d6)δppm 7.62(d,J＝8.0,2H),7.43-7.31(m,3H),7.28-7.15(m,5H),6.72(s,1H),6.50(d,J＝16.0Hz,1H),5.96(dt,J＝16.0,8.0Hz,1H),3.07(ddd,J＝80.0,12.0,8.0Hz,2H).
13 C NMR(101MHz,DMSO-d6)δppm 137.8,137.3,133.9,129.0,128.5,128.4,127.7,127.4,126.4(q,J C-F ＝262.6Hz),126.2,123.5,75.9(q,J C-F ＝26.3Hz),38.1.
19 F NMR(376MHz,DMSO-d6)δppm-78.23.
the structure of the products obtained in examples 1 to 15 was deduced from the above data:
example 16:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of p-methylphenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 94%.
The structural characterization data of the product obtained in this example are as follows:
1 H NMR(400MHz,DMSO-d6)δppm 7.60(d,J＝8.0Hz,2H),7.41-7.30(m,3H),7.10-7.04(m,4H),6.68(s,1H),6.43(d,J＝16.0Hz,1H),5.88(dt,J＝16.0,8.0Hz,1H),3.04(ddd,J＝80.0,16.0,8.0Hz,2H),2.22(s,3H).
13 C NMR(101MHz,DMSO-d6)δppm 137.3,136.5,134.1,133.3,129.1,128.0,127.9,126.9,125.9(q,J C-F ＝288.9Hz)125.7,121.9,76.0(q,J C-F ＝27.3Hz),37.7,20.7.
19 F NMR(376MHz,DMSO-d6)δppm-78.23.
the structure of the product obtained in this example is deduced from the above data:
example 17:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of o-methylphenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate to remove a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 90%.
The structural characterization data of the product obtained in this example are as follows:
1 H NMR(400MHz,DMSO-d6)δppm 7.62(d,J＝8.0Hz,2H),7.42-7.31(m,3H),7.14-7.04(m,4H),6.71(s,1H),6.65(d,J＝16.0Hz,1H),5.78(dt,J＝16.0,8.0Hz,1H),3.08(ddd,J＝84.0,16.0,8.0Hz,2H),2.13(s,3H).
13 C NMR(101MHz,DMSO-d6)δppm 137.3,136.1,134.5,131.8,123.0,128.0,127.9,127.1,127.0,126.0(q,J C-F ＝288.9Hz),126.0,125.1,124.3,76.0(q,J C-F ＝27.3Hz),37.9,19.2.
19 F NMR(376MHz,DMSO-d6)δppm-78.27.
the structure of the product obtained in this example is deduced from the above data:
example 18:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of p-methoxyphenylboric acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate to remove a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 95%.
The structural characterization data of the product obtained in this example are as follows:
1 H NMR(400MHz,DMSO-d6)δppm 7.60(d,J＝8.0Hz,2H),7.42-7.30(m,3H),7.13(d,J＝8.0Hz,2H),6.81(d,J＝8.0Hz,2H),6.66(s,1H),6.41(d,J＝16.0Hz,1H),5.78(dt,J＝16.0,8.0Hz,1H),3.70(s,3H),3.03(ddd,J＝80.0,12.0,8.0Hz,2H).
13 C NMR(101MHz,DMSO-d6)δppm 159.1,137.9,133.4,130.0,128.5,128.4,127.4,127.4,126.4(q,J C-F ＝288.9Hz),121.0,114.4,76.4(q,J C-F ＝27.3Hz),55.5,38.2.
19 F NMR(376MHz,DMSO-d6)δppm-78.20.
the structure of the product obtained in this example is deduced from the above data:
example 19:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of o-methoxyphenylboric acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate to remove a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 93%.
The structural characterization data of the product obtained in this example are as follows:
1 H NMR(400MHz,DMSO-d6)δppm 7.61(d,J＝8.0Hz,2H),7.41-7.31(m,3H),7.18-7.13(m,2H),6.92(d,J＝8.0Hz,1H),6.82(t,J＝8.0Hz,1H),6.70(d,J＝16.0Hz,1H),6.68(s,1H)5.91(dt,J＝16.0,8.0Hz,1H),3.72(s,3H),3.06(ddd,J＝80.0,12.0,8.0Hz,2H).
13 C NMR(101MHz,DMSO-d6)δppm 155.9,137.4,128.4,128.0,127.9,126.9,126.0(q,J C-F ＝287.9Hz),125.9,125.5,123.4,120.5,111.3,76.0(q,J C-F ＝26.3Hz),55.3,38.1.
19 F NMR(376MHz,DMSO-d6)δppm-78.14.
the structure of the product obtained in this example is deduced from the above data:
example 20:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of p-thiomethylphenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate to remove a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 56%.
The structural characterization data of the product obtained in this example are as follows:
1 H NMR(400MHz,DMSO-d6)δppm 7.59(d,J＝7.6Hz,2H),7.41-7.31(m,3H),7.14(s,4H),6.69(s,1H),6.43(d,J＝16.0Hz,1H),5.90(dt,J＝16.0,8.0Hz,1H),3.04(ddd,J＝80.0,16.0,8.0Hz,2H),2.42(s,3H).
13 C NMR(101MHz,DMSO-d6)δppm 137.8,137.5,134.1,133.3,128.5,128.4,127.4,126.8,126.6,126.4(q,J C-F ＝287.9Hz),76.4(q,J C-F ＝26.3Hz),38.2,15.2.
19 F NMR(376MHz,DMSO-d6)δppm-78.21.
the structure of the product obtained in this example is deduced from the above data:
example 21:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a screw scale tube equipped with a magnet, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of p-tert-butylphenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the scale tube, and the reaction system was stirred at 90℃for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate to remove a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 94%.
The structural characterization data of the product obtained in this example are as follows:
1 H NMR(400MHz,DMSO-d6)δppm 7.60(d,J＝8.0Hz,2H),7.40-7.24(m,6H),7.12(d,J＝8.4Hz,2H),6.69(s,1H),6.44(d,J＝16.0Hz,1H),5.90(dt,J＝16.0,8.0Hz,1H),3.05(ddd,J＝76.0,16.0,8.0Hz,2H),1.22(s,9H).
13 C NMR(101MHz,DMSO-d6)δppm 150.2,137.8,134.6,133.7,128.5,128.4,127.4,126.3(q,J C-F ＝287.9Hz),126.0,125.7,122.6,76.4(q,J C-F ＝27.3Hz),38.2,34.6,31.5.
19 F NMR(376MHz,DMSO-d6)δppm-78.22.
the structure of the product obtained in this example is deduced from the above data:
example 22:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a screw scale tube equipped with a magnet, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of p-chlorobenzeneboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the scale tube, and the reaction system was stirred at 90℃for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate to remove a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 80%.
The structural characterization data of the product obtained in this example are as follows:
1 H NMR(400MHz,DMSO-d6)δppm 7.60(d,J＝8.0Hz,2H),7.41-7.28(m,5H),7.21(d,J＝8.0Hz,2H),6.72(s,1H),6.48(d,J＝16.0Hz,1H),5.96(dt,J＝16.0,8.0Hz,1H),3.06(ddd,J＝84.0,16.0,8.0Hz,2H).
13 C NMR(101MHz,DMSO-d6)δppm 137.7,136.2,132.7,132.1,129.0,128.6,128.5,127.9,127.4,126.4(q,J C-F ＝287.9Hz),124.6,76.5(q,J C-F ＝26.3Hz),38.1.
19 F NMR(376MHz,DMSO-d6)δppm-78.25.
the structure of the product obtained in this example is deduced from the above data:
example 23:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of p-bromophenylboric acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate to remove a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 86%.
The structural characterization data of the product obtained in this example are as follows:
1 H NMR(400MHz,Chloroform-d)δppm 7.59(d,J＝8.0Hz,2H),7.45-7.30(m,5H),7.18-7.13(m,2H),6.72(s,1H),6.46(d,J＝16.0Hz,1H),5.97(dt,J＝16.0,8.0Hz,1H),3.05(ddd,J＝84.0,16.0,8.0Hz,2H).
13 C NMR(101MHz,DMSO-d6)δppm 136.4,135.2,131.5,130.6,127.3,127.2,127.0,126.4(q,J C-F ＝295.9Hz),126.1,123.4,119.3,75.1(q,J C-F ＝27.3Hz),36.9.
19 F NMR(376MHz,DMSO-d6)δppm-78.27.
the structure of the product obtained in this example is deduced from the above data:
example 24:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magnet, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of 3, 5-dimethylbenzeneboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for reaction for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate to remove a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 91%.
The structural characterization data of the product obtained in this example are as follows:
1 H NMR(400MHz,DMSO-d6)δppm 7.60(d,J＝8.0Hz,2H),7.41-7.30(m,3H),6.80(s,3H),6.69(s,1H),6.40(d,J＝16.0Hz,1H),5.93(dt,J＝16.0,8.0Hz,1H),3.05(ddd,J＝80.0,12.0,8.0Hz,2H),2.18(s,6H).
13 C NMR(101MHz,DMSO-d6)δppm 137.9,137.8,137.2,134.1,129.2,128.5,128.4,127.4,126.4(q,J C-F ＝287.9Hz),124.1,123.0,76.4(q,J C-F ＝27.3Hz),38.2,21.3.
19 F NMR(376MHz,DMSO-d6)δppm-78.28.
the structure of the product obtained in this example is deduced from the above data:
example 25:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of p-phenyl phenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate to remove a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 91%.
The structural characterization data of the product obtained in this example are as follows:
1 H NMR(400MHz,DMSO-d6)δppm 7.61(d,J＝8.0Hz,4H),7.56(d,J＝8.0Hz,2H),7.45-7.38(m,4H),7.35-7.28(m,4H),6.72(s,1H),6.53(d,J＝16.0Hz,1H),6.00(dt,J＝16.0,8.0Hz,1H),3.08(ddd,J＝88.0,16.0,8.0Hz,2H).
13 C NMR(101MHz,DMSO-d6)δppm 140.1,139.4,137.8,136.5,133.4,129.4,128.5,128.5,127.9,127.4,127.3,126.9,126.8,126.6(q,J C-F ＝296.9Hz),123.8,76.4(q,J C-F ＝26.3Hz),38.2.
19 F NMR(376MHz,DMSO-d6)δppm-78.20.
the single crystal diagram of the product obtained in this example is shown in FIG. 4. This single crystal picture further demonstrates that the product structure is in the E configuration.
The structure of the product obtained in this example is deduced from the above data:
example 26:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2- (4-methoxyphenyl) -4-penten-2-ol, 0.6 mmol of phenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate to remove a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 95%.
The structural characterization data of the product obtained in this example are as follows:
1 H NMR(400MHz,DMSO-d6)δppm 7.52(d,J＝8.0Hz,2H),7.27-7.15(m,5H),6.94(d,J＝8.0Hz,2H),6.61(s,1H),6.50(d,J＝16.0Hz,1H),5.98(dt,J＝16.0,8.0Hz,1H),3.74(s,3H),3.04(ddd,J＝84.0,16.0,8.0Hz,2H).
13 C NMR(101MHz,DMSO-d6)δppm 159.4,137.4,133.8,129.6,129.0,128.8,127.7,126.5(q,J C-F ＝287.9Hz),126.2,123.7,113.8,76.1(q,J C-F ＝27.3Hz),55.4,38.1.
19 F NMR(376MHz,DMSO-d6)δppm-78.62.
the structure of the product obtained in this example is deduced from the above data:
example 27:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magneton, 0.2 mmol of 1, 1-trifluoro-2- (4-methylphenyl) -4-penten-2-ol, 0.6 mmol of phenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate to remove a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 91%.
The structural characterization data of the product obtained in this example are as follows:
1 H NMR(400MHz,DMSO-d6)δppm 7.47(d,J＝8.0Hz,2H),7.27-7.15(m,7H),6.62(s,1H),6.48(d,J＝16.0Hz,1H),5.95(dt,J＝16.0.8.0.Hz,1H),3.03(ddd,J＝88.0,16.0,8.0Hz,2H),2.28(s,3H).
13 C NMR(101MHz,DMSO-d6)δppm 137.7,137.3,134.8,133.8,129.0,127.7,127.3,126.4(q,J C-F ＝287.9Hz),126.2,123.7,76.3(q,J C-F ＝27.3Hz),38.1,21.1.
19 F NMR(376MHz,DMSO-d6)δppm-78.43.
the structure of the product obtained in this example is deduced from the above data:
example 28:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a screw scale tube equipped with a magnet, 0.2 mmol of 1, 1-trifluoro-2- (4-chlorophenyl) -4-penten-2-ol, 0.6 mmol of phenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the scale tube, and the reaction system was stirred at 90℃for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate to remove a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 85%.
The structural characterization data of the product obtained in this example are as follows:
1 H NMR(400MHz,DMSO-d6)δppm 7.63(d,J＝8.0Hz,2H),7.45(d,J＝8.0Hz,2H),7.27-7.17(m,5H),6.87(s,1H),6.49(d,J＝16.0Hz,1H),5.95(dt,J＝16.0,8.0Hz,1H),3.07(ddd,J＝80.0,12.0,8.0Hz,2H).
13 C NMR(101MHz,DMSO-d6)δ137.2,136.8,134.2,133.5,129.4,129.0,128.5,127.8,126.3,126.2(q,J C-F ＝288.9Hz),123.1,76.3(q,J C-F ＝27.3Hz),38.0.
19 F NMR(376MHz,DMSO-d6)δ-78.44.
the structure of the product obtained in this example is deduced from the above data:
example 29:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magnet, 0.2 mmol of 1, 1-trifluoro-2- (4, 5-dichlorophenyl) -4-penten-2-ol, 0.6 mmol of phenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for reaction for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate to remove a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 94%.
The structural characterization data of the product obtained in this example are as follows:
1 H NMR(400MHz,DMSO-d6)δppm 7.63(m,3H),7.32-7.17(m,5H),7.12(s,1H),6.53(d,J＝16.0Hz,1H),5.94(dt,J＝16.0,8.0Hz,1H),3.10(ddd,J＝120.0,16.0,8.0Hz,2H).
13 C NMR(101MHz,DMSO-d6)δppm 142.1,137.1,134.6,134.5,129.1,128.6,127.9,126.4,126.3,126.2(q,J C-F ＝288.9Hz),122.7,76.2(q,J C-F ＝26.3Hz),37.6.
19 F NMR(376MHz,DMSO-d6)δppm-78.28.
the structure of the product obtained in this example is deduced from the above data:
example 30:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative, comprising the following steps:
to a spiral graduated tube equipped with a magnet, 0.2 mmol of 1, 1-trifluoro-2- (3, 4-dimethoxyphenyl) -4-penten-2-ol, 0.6 mmol of phenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90℃for reaction for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline solution and ethyl acetate to extract a reaction liquid, performing reduced pressure rotary evaporation on ethyl acetate to remove a solvent, and separating and purifying by column chromatography to obtain a target product, wherein the volume ratio of the used column chromatography eluent is petroleum ether of 100:1: ethyl acetate mixture; the product yield was 88%.
The structural characterization data of the product obtained in this example are as follows:
1 H NMR(400MHz,DMSO-d6)δ7.30-7.21(m,4H),7.21-7.10(m,3H),6.96(d,J＝8.5Hz,1H),6.63(s,1H),6.52(d,J＝16.0Hz,1H),5.99(dt,J＝16.0,7.0Hz,1H),3.75(s,3H),3.75(s,3H),3.05(ddd,J＝100.0,16.0,8.0Hz,2H).
13 C NMR(101MHz,DMSO-d6)δppm 149.0,148.5,137.4,133.8,130.0,129.0,127.7,126.5(q,J C-F ＝287.9Hz),126.3,123.8,120.0,111.5,111.5,76.2(q,J C-F ＝26.3Hz),56.0,55.8,38.2.
19 F NMR(376MHz,DMSO-d6)δppm-78.43.
the structure of the product obtained in this example is deduced from the above data:
the above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.
Claims (3)
1. A method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives is characterized in that: the method comprises the following steps:
reacting a 1-fluoro-2-aryl-4-penten-2-ol derivative with arylboronic acid under the action of a catalyst and oxygen by taking an organic solvent as a reaction medium to obtain a (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative;
when the 1-fluoro-2-aryl-4-pentene-2-ol derivative is 1, 1-trifluoro-2-phenyl-4-pentene-2-ol, the arylboronic acid is phenylboronic acid or p-methylphenylboronic acid or p-methoxyphenylboronic acid or o-methoxyphenylboronic acid or p-tert-butylphenylboronic acid;
when the 1-fluoro-2-aryl-4-penten-2-ol derivative is 1, 1-trifluoro-2- (4-methoxyphenyl) -4-penten-2-ol, the arylboronic acid is phenylboronic acid;
when the 1-fluoro-2-aryl-4-penten-2-ol derivative is 1, 1-trifluoro-2- (4, 5-dichlorophenyl) -4-penten-2-ol, the arylboronic acid is phenylboronic acid;
the catalyst is tetra (triphenylphosphine) palladium; the organic solvent is a mixed solvent of N, N-dimethylformamide and dimethyl sulfoxide; the volume ratio of the N, N-dimethylformamide to the dimethyl sulfoxide is 1:1, a step of;
the molar ratio of the 1-fluoro-2-aryl-4-penten-2-ol derivative to the arylboronic acid is 1:3, a step of;
the molar ratio of the catalyst to the 1-fluoro-2-aryl-4-penten-2-ol derivative is 1:20, a step of;
the reaction is carried out in an oxygen atmosphere, the reaction temperature is 90 ℃, and the reaction time is 12 hours;
the structure of the (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative is as follows:
2. the method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative according to claim 1, characterized in that: and (3) after the reaction is finished, carrying out subsequent treatment, namely cooling to room temperature after the reaction is finished, adding saline solution or water and an organic solvent, extracting a reaction liquid, carrying out reduced pressure rotary evaporation on an organic layer to remove the solvent, obtaining a crude product, and purifying by column chromatography to obtain the (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative.
3. The method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative according to claim 2, characterized in that: in the subsequent treatment, the organic solvent is ethyl acetate or dichloromethane;
the column chromatography purification refers to the purification by petroleum ether: purifying by column chromatography with mixed solvent of ethyl acetate as eluent; petroleum ether: volume ratio of ethyl acetate: (20-500): 1.
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| Fluoroalkenylation of boronic acids via an oxidative Heck reaction;Da Seul Lee and Eun Jin Cho;《Org. Biomol. Chem.》;第17卷;第4317-4325页 * |
| Highly Efficient and Reusable Polyaniline-Supported Palladium Catalysts for Open-Air Oxidative Heck Reactions under Base- and Ligand-Free Conditions;Pravin R. Likhar et al.;《Adv. Synth. Catal.》;第350卷;第1968-1974页 * |
| Mao Chen et al..C X (X=Br, I) Bond-Tolerant Aerobic Oxidative Cross- Coupling: A Strategy to Selectively Construct b-Aryl Ketones and Aldehydes.《Adv. Synth. Catal.》.2012,第354卷第341-346页. * |
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| Oxygen-Promoted Pd(II) Catalysis for the Coupling of Organoboron Compounds and Olefins;Young Chun Jung et al.;《ORGANIC LETTERS》;第5卷(第13期);第2231-2234页 * |
| Palladium-catalyzed oxidative Heck reaction of non-activated alkenes directed by fluorinated alcohol;Baiyao Zhu et al.;《Chem. Commun.》;第58卷;第12688–12691页 * |
| Practical, Broadly Applicable, α‑ Selective, Z‑ Selective, Diastereoselective, and Enantioselective Addition of Allylboron Compounds to Mono ‑ , Di ‑ , Tri ‑ , and Poly fl uoroalkyl Ketones;Farid W. van der Mei et al.;《J. Am. Chem. Soc.》;第139卷;第 9053−9065页 * |
| Reaction of trifluoromethyl ketones. III. The aluminum chloride-assisted ene reaction of 1,1,1-trifluoro-2-hexanone and α,α,α-trifluoroacetophenone;Nagai, Takabumi, et al.;《Chemical & Pharmaceutical Bulletin》;第34卷(第11期);第4782-4786页 * |
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