CN117776862A - Trifluoromethylation method of olefin - Google Patents
Trifluoromethylation method of olefin Download PDFInfo
- Publication number
- CN117776862A CN117776862A CN202311615342.XA CN202311615342A CN117776862A CN 117776862 A CN117776862 A CN 117776862A CN 202311615342 A CN202311615342 A CN 202311615342A CN 117776862 A CN117776862 A CN 117776862A
- Authority
- CN
- China
- Prior art keywords
- olefin
- trifluoromethylation
- formula
- reaction
- temperature
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000001336 alkenes Chemical class 0.000 title claims abstract description 92
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 title claims abstract description 90
- 238000006692 trifluoromethylation reaction Methods 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract description 27
- 239000002904 solvent Substances 0.000 claims abstract description 28
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 44
- 238000006243 chemical reaction Methods 0.000 claims description 44
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 33
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 24
- 230000008569 process Effects 0.000 claims description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- 239000002585 base Substances 0.000 claims description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 8
- 230000035484 reaction time Effects 0.000 claims description 8
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- 239000011261 inert gas Substances 0.000 claims description 4
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 3
- 235000010216 calcium carbonate Nutrition 0.000 claims description 3
- WUKWITHWXAAZEY-UHFFFAOYSA-L calcium difluoride Chemical compound [F-].[F-].[Ca+2] WUKWITHWXAAZEY-UHFFFAOYSA-L 0.000 claims description 3
- 229910001634 calcium fluoride Inorganic materials 0.000 claims description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 3
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 3
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 3
- 239000011736 potassium bicarbonate Substances 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 235000011181 potassium carbonates Nutrition 0.000 claims description 3
- 239000011698 potassium fluoride Substances 0.000 claims description 3
- 235000003270 potassium fluoride Nutrition 0.000 claims description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 3
- 235000017550 sodium carbonate Nutrition 0.000 claims description 3
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 3
- 239000003999 initiator Substances 0.000 abstract description 7
- 229910052755 nonmetal Inorganic materials 0.000 abstract description 5
- 239000000047 product Substances 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 7
- -1 alkenyl halides Chemical class 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
- 229920002554 vinyl polymer Polymers 0.000 description 4
- XHEOXSQMBWJOKP-UHFFFAOYSA-N 1-(trifluoromethyl)-1$l^{3},2-benziodoxol-3-one Chemical compound C1=CC=C2I(C(F)(F)F)OC(=O)C2=C1 XHEOXSQMBWJOKP-UHFFFAOYSA-N 0.000 description 3
- 229920001174 Diethylhydroxylamine Polymers 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- FVCOIAYSJZGECG-UHFFFAOYSA-N diethylhydroxylamine Chemical compound CCN(O)CC FVCOIAYSJZGECG-UHFFFAOYSA-N 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- KAVUKAXLXGRUCD-UHFFFAOYSA-M sodium trifluoromethanesulfinate Chemical compound [Na+].[O-]S(=O)C(F)(F)F KAVUKAXLXGRUCD-UHFFFAOYSA-M 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- VLSRKCIBHNJFHA-UHFFFAOYSA-N 2-(trifluoromethyl)prop-2-enoic acid Chemical compound OC(=O)C(=C)C(F)(F)F VLSRKCIBHNJFHA-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 1
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- DXDBGSMRYVGPJM-UHFFFAOYSA-N azinous acid Chemical compound ON.ON DXDBGSMRYVGPJM-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- YFXCNIVBAVFOBX-UHFFFAOYSA-N ethenylboronic acid Chemical compound OB(O)C=C YFXCNIVBAVFOBX-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000027756 respiratory electron transport chain Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a trifluoromethylation method of olefin, which comprises the following steps: the olefin, the trifluoromethylating agent and the hydroxylamine react in a solvent to obtain the trifluoromethylated product of the olefin. The method of the invention selects hydroxylamine as an initiator and non-metal promotes the trifluoromethylation of olefin under mild conditions.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a trifluoromethylation method of olefin.
Background
Olefins are one of important chemical raw materials containing carbon-carbon double bonds, and are prepared by beta-C (sp 2 ) Direct trifluoromethyl of H, can directly and efficiently construct C vinyl -CF 3 Structural units, thereby regulating the lipophilicity, binding selectivity and metabolic stability of organic compounds, are of great significance for synthesizing biologically active molecules. At present, various methods have been developed to realize C vinyl -CF 3 Synthesis of compounds, for example: (1) Pd (II) catalyzed coupling of aryl halides with 1-iodo-3, 3-trifluoropropane, 2- (trifluoromethyl) -acrylic acid; (2) Cu (I) -catalyzed vinylboronic acid and Ruppert-Prakash reagent (TMSCF) 3 ) And Langlois reagent (CF) 3 SO 2 Na) reaction; (3) CuCF (CuCF) 3 Participating in the trifluoromethylation of alkyne or alkenyl halides; (4) Ir (III) catalyzed reactions of olefins with trifluoromethyl halides, and the like. Despite metal-catalyzed olefins beta-C (sp 2 ) Great progress has been made in the direct trifluoromethylation of H, however, the non-metal promoted trifluoromethylation of olefins to C vinyl -CF 3 The compound method is still freshly researched and reported. Therefore, it is of great importance to develop a non-metal promoted olefin trifluoromethylation process.
Disclosure of Invention
The present invention has been made based on the findings and knowledge of the inventors regarding the following facts and problems: despite metal-catalyzed olefins beta-C (sp 2 ) Great progress has been made in the direct trifluoromethylation of H, however, the non-metal promoted trifluoromethylation of olefins to C vinyl -CF 3 The compound method is still freshly researched and reported.
The present invention aims to solve at least one of the technical problems in the related art to some extent. To this end, the embodiments of the present invention provide a process for the trifluoromethylation of an olefin using hydroxylamine as an initiator to promote the trifluoromethylation of the olefin under mild conditions without metals.
The embodiment of the invention provides a trifluoromethylation method of olefin, which comprises the following steps: reacting an olefin represented by formula (1), a trifluoromethylating agent and hydroxylamine in a solvent to obtain a trifluoromethylated product of the olefin represented by formula (2):
the olefin trifluoromethylation method provided by the embodiment of the invention has the advantages and technical effects that hydroxylamine is selected as an initiator, and the trifluoromethylation of the olefin is promoted under mild conditions.
In some embodiments, the hydroxylamine comprises at least one of the following structural formulas:
in some embodiments, the trifluoromethylating agent comprises at least one of the following structural formulas:
in some embodiments, the olefin of formula (1) is a terminal olefin or an internal olefin;
and/or the olefin represented by formula (1) is an inactive olefin or an active olefin.
In some embodiments, R in the olefin of formula (1) 1 、R 2 、R 3 Each independently selected from hydrogen or non-hydrogen substituents.
In some embodiments, the method further comprises reacting an olefin of formula (1), a trifluoromethylating agent, hydroxylamine, and a base in a solvent to obtain a trifluoromethylated product of the olefin of formula (2); preferably, the base comprises at least one of sodium carbonate, potassium carbonate, calcium carbonate, potassium fluoride, potassium bicarbonate, sodium monohydrogen phosphate, sodium dihydrogen phosphate, calcium fluoride.
In some embodiments, the molar ratio of olefin, trifluoromethylating agent, and hydroxylamine is from 1 to 100:1-4:0.5-4.
In some embodiments, the molar ratio of olefin to base is from 1 to 100:0-4.
In some embodiments, the temperature of the reaction is 86-150 ℃;
and/or the reaction time is 7-72h;
and/or, the reaction is carried out under an inert gas atmosphere.
In some embodiments, the reaction comprises: carrying out a first-stage reaction at a first temperature, and then raising the temperature to a second temperature to carry out a second-stage reaction to obtain a trifluoromethylated product of the olefin shown in the formula (2);
preferably, the temperature of the first stage reaction is 60-85 ℃; the reaction time of the first stage is 1-6h; the temperature of the second-stage reaction is 140-170 ℃; the second stage reaction time is 7-72h.
In some embodiments, the solvent comprises at least one of acetonitrile, tetrahydrofuran, 1, 4-dioxane, N-dimethylformamide, dimethyl sulfoxide, ethylene glycol dimethyl ether, ethylene glycol monomethyl ether.
Detailed Description
The following detailed description of embodiments of the invention is exemplary and intended to be illustrative of the invention and not to be construed as limiting the invention.
The trifluoromethylation method of the olefin comprises the following steps: reacting an olefin represented by formula (1), a trifluoromethylating agent and hydroxylamine (hydroxyamine) in a solvent to obtain a trifluoromethylated product of the olefin represented by formula (2):
according to the olefin trifluoromethyl method, hydroxylamine is selected as an initiator, and nonmetal is used for promoting olefin trifluoromethyl under mild conditions.
In some embodiments, the hydroxylamine comprises at least one of the following structural formulas:
preferably, diethylhydroxylamine (Et 2 NOH)：
In the embodiment of the invention, the used initiator has a simple structure, and is beneficial to further promoting the trifluoromethylation reaction of olefin. The diethylhydroxylamine is colorless transparent liquid, the reagent is cheap and easy to obtain, is insensitive to water and oxygen, is easy to store and use, is easy to dissolve in water, is easy to separate from a reaction system, and is favorable for further efficiently promoting the trifluoromethylation reaction of olefin.
In some embodiments, the trifluoromethylating agent comprises at least one of the following structural formulas:
wherein OTf - Is trifluoro methanesulfonic acid anion CF 3 SO 3 - ；
Preferably, the trifluoromethylating agent comprises Togni reagent II:
in the embodiment of the invention, a stable and convenient-to-operate trifluoromethyl reagent is used as a trifluoromethyl radical precursor to realize the trifluoromethyl of olefin.
In some embodiments, the olefin of formula (1) is a terminal olefin or an internal olefin; and/or the olefin represented by the formula (1) is a non-activated olefinOr activating an olefin; preferably, R in the olefin represented by formula (1) 1 、R 2 、R 3 Each independently selected from hydrogen or non-hydrogen substituents; further preferably, R in the olefin represented by the formula (1) 1 Selected from alkyl, aryl, heteroaryl, ester, and amide groups; r is R 2 Selected from hydrogen, alkyl, aryl, optionally, the alkyl is selected from methyl, ethyl, and the aryl is selected from phenyl; r is R 3 Selected from hydrogen, alkyl, optionally, the alkyl is methyl. In the embodiment of the invention, the olefin trifluoromethyl method has wide applicability to olefin.
In some embodiments, the molar ratio of olefin, trifluoromethylating agent, and hydroxylamine is from 1 to 100:1-4:0.5-4, specifically, for example, 1:2.5:2,5:4:4,9:4:4,10: 4:4.
in some embodiments, the method further comprises reacting an olefin of formula (1), a trifluoromethylating agent, hydroxylamine, and a base in a solvent to obtain a trifluoromethylated product of the olefin of formula (2);
preferably, the base comprises at least one of sodium carbonate, potassium carbonate, calcium carbonate, potassium fluoride, potassium bicarbonate, sodium monohydrogen phosphate, sodium dihydrogen phosphate, calcium fluoride; further preferred is sodium carbonate. In the embodiment of the invention, when no alkali is added, the olefin shown in the formula (1), the trifluoromethylating reagent and the hydroxylamine can react to obtain the trifluoromethylated product of the olefin shown in the formula (2). The addition of the base can promote the reaction, because the base and hydroxylamine (such as diethyl hydroxylamine) act, the electron donating ability of the hydroxylamine is improved, the single electron transfer reaction of the hydroxylamine and the trifluoromethylating agent is promoted, and the generated trifluoromethyl free radical is added to the olefin, so that the reaction yield is improved. The hydroxylamine/alkali combination is selected as an initiator, the initiator has a simple structure, the inorganic alkali is cheap and stable, the use of strong alkali is avoided, and the non-transition metal promotes the trifluoromethylation of the olefin under the mild condition.
In some embodiments, the molar ratio of olefin to base is from 1 to 100:0-4, optionally 1-100:0.1-4, specifically, for example, 1:2,2:2,5:4, a step of; the molar ratio of the olefin, the trifluoromethylating agent, the hydroxylamine and the alkali is 1-100:1-4:0.5-4:0-4, specifically, for example, 1:2.5:2:2.
in some embodiments, the temperature of the reaction is 86-150 ℃, specifically, for example, 86 ℃,90 ℃,100 ℃,110 ℃,120 ℃,130 ℃,140 ℃,150 ℃, preferably 150 ℃; and/or the reaction time is 7-72h, specifically, for example, 7h,12h,24h,48h,60h,72h. In the embodiment of the invention, the experimental study shows that under the low-temperature condition (for example, 60 ℃), the oxidized trifluoromethyl product of the olefin is taken as the main product, but as the reaction temperature is increased, the proportion of the trifluoromethyl product of the olefin is gradually increased, the temperature is continuously increased, for example, the temperature is increased to 150 ℃, and only the trifluoromethyl product of the olefin is found for the product characterization after the reaction is finished. Wherein the structural formula of the hydroxylamine is (R) 2 In the case of NOH, the structural formula of the olefin oxide trifluoromethyl product is shown as follows:
in some embodiments, the reaction is performed under an inert gas atmosphere, preferably, the inert gas is argon.
In some embodiments, the reaction comprises: carrying out a first-stage reaction at a first temperature, and then raising the temperature to a second temperature to carry out a second-stage reaction to obtain a trifluoromethylated product of the olefin shown in the formula (2); preferably, the temperature of the first stage reaction is from 60 to 85 ℃, in particular, for example, 60 ℃,65 ℃,70 ℃,75 ℃,80 ℃,85 ℃; the time of the first stage reaction is 1 to 6 hours, specifically, for example, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours; the temperature of the second stage reaction is 140-170 ℃, specifically, for example, 140 ℃,150 ℃,160 ℃,170 ℃; the second stage reaction time is 7 to 72 hours, specifically, for example, 7 hours, 12 hours, 24 hours, 48 hours, 60 hours, 72 hours. In the embodiment of the invention, the reaction preferably comprises two reaction stages, so that the trifluoromethylated product of olefin can be efficiently obtained, and the yield is further improved.
In some embodiments, the solvent comprises at least one of acetonitrile, tetrahydrofuran, 1, 4-dioxane, N-dimethylformamide, dimethyl sulfoxide, ethylene glycol dimethyl ether, ethylene glycol monomethyl ether.
In some embodiments, the solvent is N, N-dimethylformamide.
In some embodiments, the solvent comprises acetonitrile, tetrahydrofuran, and N, N-dimethylformamide, preferably, the volume ratio of acetonitrile, tetrahydrofuran, and N, N-dimethylformamide is 1:2:3.
in some embodiments, the solvent comprises acetonitrile and 1, 4-dioxane, the volume ratio of acetonitrile to 1, 4-dioxane being from 1 to 10:10-1, specifically, for example, 1:10,1:5,1:2,1:1,2:1,5:1,10: 1.
in some embodiments, the first stage reaction is performed in a first solvent.
In some embodiments, the first solvent comprises at least one of acetonitrile, tetrahydrofuran, 1, 4-dioxane; preferably, the first solvent comprises acetonitrile and tetrahydrofuran, and the volume ratio of acetonitrile to tetrahydrofuran is 1-10:10-1, specifically, for example, 1:10,1:5,1:2,1:1,2:1,5:1,10: 1, preferably 1:2; and/or the first solvent comprises acetonitrile and 1, 4-dioxane, and the volume ratio of the acetonitrile to the 1, 4-dioxane is 1-10:10-1, specifically, for example, 1:10,1:5,1:2,1:1,2:1,5:1,10: 1.
in some embodiments, a second solvent is added to the second stage reaction, preferably, the second solvent is N, N-dimethylformamide.
In some embodiments, the first stage reaction is performed at a first temperature, cooled to room temperature, a second solvent is added, and then warmed to a second temperature to perform the second stage reaction.
In some embodiments, the first solvent comprises acetonitrile and tetrahydrofuran in a volume ratio of 1:2; the second solvent is N, N-dimethylformamide; the volume ratio of the first solvent to the second solvent is 1:1, namely acetonitrile, tetrahydrofuran and N, N-dimethylformamide in a volume ratio of 1:2:3.
in some embodiments, the ratio of the amount of material of the olefin to the volume of solvent is 0.1mmol:0.1mL-0.1mmol:10mL, specifically, for example, 0.1mmol:0.1mL,0.1mmol:0.2mL,0.1mmol:0.5mL,0.1mmol:1mL,0.1mmol:2mL,0.1mmol:5mL,0.1mmol:8mL,0.1mmol:10mL.
In some embodiments, the ratio of the amount of material of the olefin to the volume of solvent in the first stage reaction is 0.1mmol:0.1ml to 0.1mmol:5ml, specifically, for example, 0.1mmol:0.1ml,0.1mmol:0.2ml,0.1mmol:0.5ml,0.1mmol:1ml,0.1mmol:2ml,0.1mmol:5ml; in the second stage reaction, the ratio of the amount of the substance of the olefin to the volume of the solvent is 0.1mmol:0.2mL-0.1mmol:10mL, specifically, for example, 0.1mmol:0.2mL,0.1mmol:1mL,0.1mmol:2mL,0.1mmol:5mL,0.1mmol:8mL,0.1mmol:10mL.
In some embodiments, the reaction product is washed with water, then the aqueous phase is extracted with methylene chloride, the organic solvent is dried, spin-dried, and subjected to silica gel column separation and/or thin layer plate chromatography to obtain the trifluoromethylated product of the olefin represented by formula (2).
The invention will now be described with reference to specific examples, which are intended to be illustrative only and not limiting in any way.
The first embodiment is as follows:
trifluoromethylation reagent Togni reagent II (2.5 mmol) and Et 2 NOH (2.0 mmol), olefin (1.0 mmol) 1mL of a 1/2 mixed solution of MeCN and THF was added to the reaction tube under Ar atmosphere, reacted at 80℃for 2 hours, cooled to room temperature and DMF (1 mL) was added thereto, and the temperature was raised to 150℃to finish the reaction for about 24 hours. After the reaction, benzotrifluoride was added as an internal standard, and the fluorine spectrum showed the compound yield as shown below. On this basis, about 3X 3mL of deionized water was added to wash off DMF and the aqueous phase was extracted with dichloromethane and the organics were dried over anhydrous sodium sulfateThe solvent was spin dried, and the product was isolated by silica gel column separation and preparative thin layer plate chromatography as shown in example 1.
Example 1:
the yield was 76%.
1 H NMR(400MHz,CDCl 3 )δ7.67(dd,J＝7.9,4.4Hz,4H),7.54(dd,J＝23.7,7.8Hz,4H),7.45(d,J＝7.2Hz,1H),7.31-7.20(m,1H),6.29(dq,J＝16.1,6.5Hz,1H).
19 F NMR(376MHz,CDCl 3 )δ-63.12(d,J＝6.8Hz).
The second embodiment is as follows:
olefin trifluoromethyl product synthesis:
sodium carbonate (0.2 mmol), trifluoromethylating reagent Togni reagent II (0.25 mmol) and Et 2 NOH (0.2 mmol), olefin (0.1 mmol) was reacted under Ar atmosphere. After the reaction, about 3×3mL of deionized water was added to wash off DMF, and the aqueous phase was extracted with dichloromethane, the organic solvent was dried over anhydrous sodium sulfate, spin-dried, and the product was separated on a silica gel column to give the product in the following yields and shown in examples 2 and 3. Wherein, the reactions are respectively as follows:
a the reaction was carried out in DMF (1 mL) at 150℃for 7-72 hours.
b 1mL of a 1/2 mixed solution of MeCN and THF was added to the reaction tube, and after reacting at 80℃for 2 hours, DMF (1 mL) was added thereto after cooling to room temperature, and the temperature was raised to 150℃for 7-72 hours.
c DMF (1 mL) was added to the reaction tube, reacted at 80℃for 2 hours, and heated to 150℃for 7-72 hours.
Example 2:
the yield was 96%.
1 H NMR(400MHz,CDCl 3 )δ7.67(dd,J＝7.9,4.4Hz,4H),7.54(dd,J＝23.7,7.8Hz,4H),7.45(d,J＝7.2Hz,1H),7.31-7.20(m,1H),6.29(dq,J＝16.1,6.5Hz,1H).
19 F NMR(376MHz,CDCl 3 )δ-63.12(d,J＝6.8Hz).
Example 3:
the yield was 98%.
1 H NMR(400MHz,CDCl 3 )δ7.48-7.33(m,4H),7.16(t,J＝7.5Hz,1H),7.13-7.07(m,1H),7.07-7.01(m,2H),7.02-6.94(m,2H),6.10(dq,J＝16.1,6.5Hz,1H).
19 F NMR(376MHz,CDCl 3 )δ-63.02(dd,J＝6.8,2.3Hz).
For purposes of this disclosure, the terms "one embodiment," "some embodiments," "example," "a particular example," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, schematic representations of the above terms are not necessarily directed to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, the different embodiments or examples described in this specification and the features of the different embodiments or examples may be combined and combined by those skilled in the art without contradiction.
While the above embodiments have been shown and described, it should be understood that the above embodiments are illustrative and not to be construed as limiting the invention, and that variations, modifications, alternatives, and variations of the above embodiments may be made by those of ordinary skill in the art without departing from the scope of the invention.
Claims (10)
1. A process for the trifluoromethylation of an olefin comprising: reacting an olefin represented by formula (1), a trifluoromethylating agent and hydroxylamine in a solvent to obtain a trifluoromethylated product of the olefin represented by formula (2):
2. the process for the trifluoromethylation of an olefin according to claim 1, wherein the hydroxylamine comprises at least one of the following structural formulas:
3. the process for the trifluoromethylation of an olefin according to claim 1, wherein the trifluoromethylating agent comprises at least one of the following structural formulas:
4. the process for the trifluoromethylation of an olefin according to claim 1, wherein the olefin represented by formula (1) is a terminal olefin or an internal olefin;
and/or the olefin represented by formula (1) is an inactive olefin or an active olefin.
5. The process for the trifluoromethylation of an olefin according to claim 1, wherein R in the olefin represented by the formula (1) 1 、R 2 、R 3 Each independently selected from hydrogen or non-hydrogen substituents.
6. The process for the trifluoromethylation of an olefin according to claim 1, further comprising reacting an olefin represented by formula (1), a trifluoromethylating agent, hydroxylamine and a base in a solvent to obtain a trifluoromethylated product of an olefin represented by formula (2); the alkali comprises at least one of sodium carbonate, potassium carbonate, calcium carbonate, potassium fluoride, potassium bicarbonate, sodium monohydrogen phosphate, sodium dihydrogen phosphate and calcium fluoride.
7. The process for the trifluoromethylation of an olefin according to claim 1 or 6, wherein the molar ratio of olefin, trifluoromethylating agent and hydroxylamine is from 1 to 100:1-4:0.5-4;
and/or the molar ratio of the olefin to the base is 1-100:0-4.
8. The process for the trifluoromethylation of an olefin according to claim 1 or 6, wherein the temperature of the reaction is 86-150 ℃;
and/or the reaction time is 7-72h;
and/or, the reaction is carried out under an inert gas atmosphere.
9. The process for the trifluoromethylation of an olefin according to claim 1 or 6, wherein the reaction comprises: carrying out a first-stage reaction at a first temperature, and then raising the temperature to a second temperature to carry out a second-stage reaction to obtain a trifluoromethylated product of the olefin shown in the formula (2);
preferably, the temperature of the first stage reaction is 60-85 ℃; the reaction time of the first stage is 1-6h; the temperature of the second-stage reaction is 140-170 ℃; the second stage reaction time is 7-72h.
10. The method for trifluoromethylating an olefin according to claim 1 or 6, wherein said solvent comprises at least one of acetonitrile, tetrahydrofuran, 1, 4-dioxane, N-dimethylformamide, dimethyl sulfoxide, ethylene glycol dimethyl ether, and ethylene glycol monomethyl ether.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311615342.XA CN117776862A (en) | 2023-11-29 | 2023-11-29 | Trifluoromethylation method of olefin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311615342.XA CN117776862A (en) | 2023-11-29 | 2023-11-29 | Trifluoromethylation method of olefin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117776862A true CN117776862A (en) | 2024-03-29 |
Family
ID=90400725
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311615342.XA Pending CN117776862A (en) | 2023-11-29 | 2023-11-29 | Trifluoromethylation method of olefin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117776862A (en) |
-
2023
- 2023-11-29 CN CN202311615342.XA patent/CN117776862A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2020147861A1 (en) | Electrochemical preparation method for β-trifluoromethylamide compound | |
| CN114409515B (en) | Preparation method of gem-difluoroolefin compound | |
| Zhang et al. | Cu-catalyzed chlorotrifluoromethylation of alkenes with CF3SO2Cl | |
| CN114634482A (en) | Diazo difluoromethylation reagent and synthesis method and application thereof | |
| TW202233569A (en) | Processes of preparing 3-fluoro-5-(((1s,2ar)-1,3,3,4,4-pentafluoro-2a-hydroxy-2,2a,3,4-tetrahydro-1h-cyclopenta[cd]inden-7-yl)oxy)-benzonitrile | |
| CN117776862A (en) | Trifluoromethylation method of olefin | |
| JP2010030991A (en) | Method for producing 3-methyl-2-thiophenecarboxylic acid | |
| CN111269074A (en) | Preparation method of α -halogenated trifluoromethyl substituted alkane | |
| CN115073377A (en) | Method for preparing N-arylpyrazole compound by iodine catalytic oxidation method and product thereof | |
| CN114805069B (en) | Method for synthesizing alpha difluoro ester derivative from terminal olefin | |
| CN106892866B (en) | 1, 2-disubstituted-4-quinolone and synthesis method thereof | |
| CN112679328B (en) | Industrial production method of 3-trifluoromethyl-2-cyclohexene-1-one | |
| TW296381B (en) | ||
| JPH0156054B2 (en) | ||
| CN111196786B (en) | Trifluoromethanesulfonyl substituted isoxazole compound and synthesis method thereof | |
| CN115466158B (en) | 1, 3-triaryl-1, 3-butadiene derivative and synthesis method thereof | |
| CN115028505B (en) | Preparation method of beta, beta-di (hetero) aryl-alpha, alpha-difluoro ketone compound | |
| JP3279801B2 (en) | New method for producing carboxylic acid ester | |
| JP2008297234A (en) | Method for producing bromotetrafluoroalkanol | |
| WO2022095823A1 (en) | Functionalized fluoroalkyl silane, and synthetic method therefor and application thereof | |
| JP2004115377A (en) | Method for producing fluorine-containing carboxylic acid derivative | |
| JP4093842B2 (en) | Method for producing halogenated adamantanes | |
| Xiao et al. | The Chemistry of Tetrafluoroallene: One‐pot Synthesis of Trifluoromethylindolizines from 1, 3‐Diiodo‐1, 1, 3, 3‐tetrafluoropropane by 1, 3‐Dipolar Cycloaddition | |
| JP4243683B2 (en) | Method for producing 1-tetralone | |
| JP4105482B2 (en) | Process for producing trihalo-substituted aromatic compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |