CN106008402A - Epsilon-trifluoromethyl substituted amide preparing method - Google Patents
Epsilon-trifluoromethyl substituted amide preparing method Download PDFInfo
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- 150000001408 amides Chemical class 0.000 title claims abstract description 16
- 238000000034 method Methods 0.000 title claims abstract 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims abstract description 42
- 238000006243 chemical reaction Methods 0.000 claims abstract description 42
- -1 2-allyl benzaldehyde compound Chemical class 0.000 claims abstract description 9
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- 239000010949 copper Substances 0.000 claims abstract description 7
- HVAPLSNCVYXFDQ-UHFFFAOYSA-N 3,3-dimethyl-1-(trifluoromethyl)-1$l^{3},2-benziodoxole Chemical compound C1=CC=C2C(C)(C)OI(C(F)(F)F)C2=C1 HVAPLSNCVYXFDQ-UHFFFAOYSA-N 0.000 claims abstract description 6
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052802 copper Inorganic materials 0.000 claims abstract description 6
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 238000012805 post-processing Methods 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 37
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 22
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 22
- 238000002360 preparation method Methods 0.000 claims description 5
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 3
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical group [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 238000004587 chromatography analysis Methods 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 4
- 229930014626 natural product Natural products 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 162
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Natural products O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 36
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 27
- 238000005160 1H NMR spectroscopy Methods 0.000 description 27
- 238000004293 19F NMR spectroscopy Methods 0.000 description 26
- 239000007788 liquid Substances 0.000 description 26
- 238000011017 operating method Methods 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 238000006692 trifluoromethylation reaction Methods 0.000 description 6
- 150000001336 alkenes Chemical class 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 238000007306 functionalization reaction Methods 0.000 description 4
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 208000035126 Facies Diseases 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- 229910020323 ClF3 Inorganic materials 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 0 *c1ccccc1CC=C Chemical compound *c1ccccc1CC=C 0.000 description 1
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 1
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N C1NCCOC1 Chemical compound C1NCCOC1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- IRNZVYPDHAYKEO-UHFFFAOYSA-N O=C(c1ccccc1CCCC(F)(F)F)N1CCOCC1 Chemical compound O=C(c1ccccc1CCCC(F)(F)F)N1CCOCC1 IRNZVYPDHAYKEO-UHFFFAOYSA-N 0.000 description 1
- XHEOXSQMBWJOKP-UHFFFAOYSA-O O=C1[OH+][I](C(F)(F)F)c2ccccc12 Chemical compound O=C1[OH+][I](C(F)(F)F)c2ccccc12 XHEOXSQMBWJOKP-UHFFFAOYSA-O 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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 125000000746 allylic group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000006178 methyl benzyl group Chemical group 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
- C07D317/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Abstract
The invention relates to an Epsilon-trifluoromethyl substituted amide preparing method. The preparing method comprises the steps of dissolving a copper catalyst, alkali and a togni reagent into organic solvent, adding 2-allyl benzaldehyde compound and pyrrolidine to form a reacting system, enabling the reacting system to react for 10 hours at room temperature and post-processing to obtain the epsilon-trifluoromethyl substituted amide. The preparing method is good in reaction yield and has good application prospect on synthesizing epsilon-trifluoromethyl substituted amide natural products or medicine.
Description
Technical field
The invention belongs to organic synthesis field, be specifically related to the preparation method of a kind of ε-trifluoromethyl substituted amide.
Background technology
Compound containing trifluoromethyl is widely used in the fields such as medicine, pesticide and material, and research shows, trifluoromethyl (CF3) there is the characteristic such as the most electron-withdrawing, lipotropy and stable C-F key, it is introduced in organic compound and can significantly change its acidity, dipole moment, polarity, lipotropy and chemistry and metabolic stability.Under the promotion of Organometallic Chemistry research, the direct trifluoromethylation reaction of c h bond obtains important breakthrough, and 2011, Buchwald etc. found at [(MeCN)4Cu]-PF6Catalysis under, electrophilic trifluoromethylation Togni reagent and non-activated olefine reaction can generate the allyl compound of trifluoromethylation.So far, the difunctionality dough type trifluoromethylation reaction of olefinic double bonds is widely applied, and can build C-CF by one kettle way simultaneously3Key and C-Z key (Z is carbon, oxygen, nitrogen or halogen).
Liu Xinyuan, Tan Bin seminar has carried out a series of CF around disactivation alkene trifluoromethylation3Free radical causes non-reactive olefin and long-range sp3The research work of c h bond functionalization.But, the sp of this type of reaction2C h bond official can dough not appear in the newspapers.
Amide group is many natural products and the core texture unit with bioactive compound, and the synthesis of ε-trifluoromethyl substituted amide has great significance to expanding the amide molecule (including medicine, pesticide, fine chemicals and intermediate thereof etc.) with special chemical function.Development CF3Free radical causes non-reactive olefin and long-range sp2The Bifunctionalized research work of c h bond, can synthesize ε-trifluoromethyl substituted amide efficiently.
Summary of the invention
The invention provides a kind of by CF3Free radical causes the functionalization of non-reactive olefin and long-range sp2The functionalization of c h bond, one kettle way has efficiently built the preparation method of the substituted amide compound of ε-trifluoromethyl, and reaction yield is good, has a good application prospect for synthesis ε-trifluoromethyl substituted amide class natural product or medicine.
The preparation method of a kind of ε-trifluoromethyl substituted amide, comprises the steps:
Copper catalyst, alkali and the toghni reagent shown in structure formula III are dissolved in organic solvent, add the 2-allyl benzene benzaldehyde compound shown in structure formula II and pyrrolidine forms reaction system, reaction system is at room temperature reacted 10 hours, the post-treated ε-trifluoromethyl substituted amide obtained shown in structural formula I.
Described togni reagent is 1-(trifluoromethyl)-1,2-benzenesulfonyl-3 (1H)-one, and structure is as shown in formula III:
Described 2-allyl benzene benzaldehyde compound structure is as shown in formula II:
Described ε-trifluoromethyl substituted amide structure is as shown in formula I:
In formula I and formula II, R1For hydrogen atom, methyl, methoxyl group, methylene-dioxy, fluorine atom, chlorine atom, phenyl, p-methylphenyl, p-methoxyphenyl or thienyl.
Described alkali is potassium carbonate, and described catalyst is copper sulfate, and described organic solvent is DMF.
The mol ratio of the compound shown in described copper catalyst, alkali, togni reagent, structure formula II and pyrrolidine is 0.1:1.5:1.5:1:1.5.
Described reaction only need at room temperature be carried out, and the optimum response time is 10 hours.
The reaction scheme of optimum condition is as follows:
Described reaction uses that the cancellation that adds water, extraction, organic facies are scrubbed the most afterwards, be dried and the technology such as column chromatography for separation carries out post processing, to obtain highly purified product.
Described extraction can use ethyl acetate as extractant.
Described washing can use saturated common salt to wash.
The condition of described column chromatography for separation is: silica gel 300-400 mesh, eluent: the volume ratio of petrol ether/ethyl acetate is 3/1.
The pyrrolidine told is equally applicable to piperidines, the ring-type aminated compounds of piperazine or dibenzyl, diethyl, dicyclohexyl, diisopropyl, methyl-benzyl, methyl butyl aminated compounds.
The 2-allyl benzene benzaldehyde compound told is equally applicable to the 2-allyl benzene benzaldehyde compound that allylic contains methyl, ethyoxyl or ester group.
Compared with the existing technology, present invention have the advantage that 1, realize the long-range sp that non-reactive olefin trifluoromethylation causes first2C h bond functionalization；2, reaction concurrently forms carbon-trifluoromethyl and amide chemical bond, has atom and the step economy of height；3, achieving the synthesis of a series of ε-trifluoromethyl substituted amide, wide application range of substrates, functional group compatibility is good, and reaction is at room temperature carried out, simple to operate, has applications well prospect.Therefore the present invention has bigger theory innovation value and implementary value.
Detailed description of the invention
Embodiment 1
Take a dry reaction tube, it is weighed into copper sulfate (4.0mg, 0.025mmol), potassium carbonate (52mg, 0.375mmol), 1-(trifluoromethyl)-1,2-benzenesulfonyl-3 (1H)-one I (118.5mg, 0.375mmol), evacuation changes nitrogen, replace three times, it is subsequently adding and is dissolved in 2mL N, 2-allyl benzene formaldehyde 1a (36.5mg, 0.25mmol) and pyrrolidine 2a (26.0mg, 0.375mmol) of dinethylformamide.After reaction is stirred at room temperature 10h, adding 10mL shrend and go out, extract three times by ethyl acetate (10mL), wash organic facies with saturated drinkable water after merging, anhydrous sodium sulfate is dried.Organic facies obtains 57mg colourless liquid 3aa, yield 80% by silica gel (300-400 mesh) column chromatography for separation (eluent: the volume ratio of petrol ether/ethyl acetate is 3/1) after concentrating.Product nmr analysis1H NMR(400MHz,CDCl3) δ 7.35 7.18 (m, 4H), 3.65 (t, J=7.0Hz, 2H), 3.15 (t, J=6.7Hz, 2H), 2.72 (t, J=7.7Hz, 2H), 2.18 2.03 (m, 2H), 2.01 1.81 (m, 6H)；13C NMR(100MHz,CDCl3) δ 169.5,137.4,137.0,131.2,129.0,127.1 (q, J=274.9Hz), 126.4,126.1,48.7,45.4,33.2 (q, J=28.3Hz), 31.7,25.9,24.5,23.0 (q, J=2.9Hz)；19F NMR(375MHz,CDCl3)δ–66.2；HRMS(ESI)calcd for C15H19F3NO(M+H)+286.1419, found286.1417. reaction equation is as follows:
Embodiment 2
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1b, remaining operating procedure is with embodiment 1, productivity: 81%, colourless liquid.1H NMR(600MHz,CDCl3) δ 7.14 7.08 (m, 1H), 7.06 7.00 (m, 2H), 3.64 (t, J=7.1Hz, 2H), 3.16 (t, J=6.7Hz, 2H), 2.69 (t, J=7.7Hz, 2H), 2.34 (s, 3H), 2.15 2.05 (m, 2H), 1.99 1.92 (m, 2H), 1.88 1.81 (m, 4H)；13C NMR(151MHz,CDCl3) δ 169.7,138.9,137.2,134.6,130.2,127.1 (q, J=274.9Hz), 127.0,126.1,48.8,45.4,33.3 (q, J=28.4Hz), 31.8,26.0,24.6,23.1 (q, J=2.8Hz), 21.3；19F NMR(565MHz,CDCl3)δ–66.2；HRMS(ESI)calcd for C16H21F3NO(M+H)+300.1575,found300.1571.
Reaction equation is as follows:
Embodiment 3
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1c, remaining operating procedure is with embodiment 1, productivity: 75%, colourless liquid；1H NMR(600MHz,CDCl3) δ 7.14 (d, J=8.5Hz, 1H), 6.86 (dd, J=8.5,2.7Hz, 1H), 6.76 (d, J=2.7Hz, 1H), 3.79 (s, 3H), 3.64 (t, J=7.1Hz, 2H), 3.16 (t, J=6.7Hz, 2H), 2.64 (t, J=7.7Hz, 2H), 2.12 2.03 (m, 2H), 2.00 1.93 (m, 2H), 1.90 1.81 (m, 4H)；13C NMR(151MHz,CDCl3) δ 169.2,158.0,138.4,130.7,128.8,127.1 (q, J=276.5Hz), 114.7,111.4,55.4,48.7,45.4,33.2 (q, J=28.4Hz), 30.9,25.9,24.5,23.2 (q, J=2.8Hz)；19F NMR(565MHz,CDCl3)δ–66.1；HRMS(ESI)calcd for C16H21F3NO2(M+H)+316.1524,found 316.1522.
Reaction equation is as follows:
Embodiment 4
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1d, remaining operating procedure is with embodiment 1, productivity: 84%, colourless liquid；1H NMR(600MHz,CDCl3) δ 7.20 7.14 (m, 1H), 6.79 6.73 (m, 2H), 3.81 (s, 3H), 3.63 (t, J=7.0Hz, 2H), 3.18 (t, J=6.7Hz, 2H), 2.72 (t, J=7.7Hz, 2H), 2.15 2.05 (m, 2H), 1.98 1.94 (m, 2H), 1.88 1.82 (m, 4H)；13C NMR(151MHz,CDCl3) δ 169.5,159.9,139.4,130.0,127.7,127.1 (q, J=276.6Hz), 115.2,111.3,55.2,48.9,45.4,33.2 (q, J=28.4Hz), 32.0,26.0,24.5,23.0 (q, J=2.9Hz)；NMR(565MHz,CDCl3)δ–66.2；HRMS(ESI)calcd for C16H21F3NO2(M+H)+316.1524, found 316.1524. reaction equation is as follows:
Embodiment 5
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1e, remaining operating procedure is with embodiment 1, productivity: 70%, colourless liquid；1H NMR(600MHz,CDCl3) δ 6.72 6.68 (m, 2H), 5.97 (s, 2H), 3.62 (t, J=7.0Hz, 2H), 3.18 (t, J=6.7Hz, 2H), 2.63 (t, J=7.6Hz, 2H), 2.13 2.05 (m, 2H), 1.99 1.94 (m, 2H), 1.89 1.80 (m, 4H)；13C NMR(151MHz,CDCl3) δ 169.0,148.1,145.9,131.4,130.6,127.1 (q, J=276.6Hz), 109.5,106.4,101.3,48.8,45.5,33.1 (q, J=28.5Hz), 31.6,26.0,24.5,23.3 (q, J=2.7Hz)；19F NMR(565MHz,CDCl3)δ–66.1；HRMS(ESI)calcd for C16H19F3NO3(M+H)+330.1317,found 330.1301.
Reaction equation is as follows:
Embodiment 6
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1f, remaining operating procedure is with embodiment 1, productivity: 85%, colourless liquid；1H NMR(600MHz,CDCl3) δ 7.21 (dd, J=8.5,5.3Hz, 1H), 7.06 7.00 (m, 1H), 6.94 (dd, J=8.5,2.7Hz, 1H), 3.64 (t, J=7.1Hz, 2H), 3.16 (t, J=6.7Hz, 2H), 2.68 (t, J=7.8Hz, 2H), 2.15 2.04 (m, 2H), 2.01 1.93 (m, 2H), 1.91 1.81 (m, 4H)；13C NMR(151MHz,CDCl3) δ 168.0 (d, J=2.1Hz), 161.0 (d, J=246.9Hz), 138.9 (d, J=6.4Hz), 132.9 (d, J=3.5Hz), 131.2 (d, J=7.8Hz), 127.0 (q, J=276.2Hz), 116.0 (d, J=21.0Hz), 113.1 (d, J=22.6Hz), 48.7,45.5,33.2 (q, J=28.6Hz), 31.1,25.9,24.5, (23.2 q, J=3.0Hz)；19F NMR(565MHz,CDCl3)δ–66.2,–115.7；HRMS(ESI)calcd for C15H18F4NO(M+H)+304.1325,found 304.1315.
Reaction equation is as follows:
Embodiment 7
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1g, remaining operating procedure is with embodiment 1, productivity: 59%, colourless liquid；1H NMR(600MHz,CDCl3)δ7.32–7.27(m,1H),7.06–7.01(m,1H),7.00–6.95(m 1H),3.76–3.69(m,1H),3.66–3.59(m,1H),3.34–3.27(m,1H),3.11–3.05(m,1H),2.88–2.81(m,1H),2.62–2.53(m,1H),2.17–2.05(m,2H),2.02–1.82(m,6H)；13C NMR(151MHz,CDCl3) δ 164.4 (d, J=1.1Hz), 158.3 (d, J=245.8Hz), 130.2 (d, J=8.5Hz), 127.0 (q, J=276.6Hz), 125.6 (d, J=19.2Hz), 125.0 (d, J=2.9Hz), 113.6 (d, J=21.8Hz), 47.5 (d, J=2.1Hz), (45.4,33.2 q, J=28.6Hz), 31.7,31.7,25.7,24.5, (22.9 q, J=2.8Hz)；19F NMR(565MHz,CDCl3)δ–66.2,–116.8；HRMS(ESI)calcd for C15H18F4NO(M+H)+304.1325,found 304.1312.
Reaction equation is as follows:
Embodiment 8
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1h, remaining operating procedure is with embodiment 1, productivity: 78%, colourless liquid；1H NMR(600MHz,CDCl3) δ 7.29 (dd, J=8.3,2.2Hz, 1H), 7.22 (d, J=2.2Hz, 1H), 7.18 (d, J=8.3Hz, 1H), 3.64 (t, J=7.1Hz, 2H), 3.17 (t, J=6.7Hz, 2H), 2.68 (t, J=7.8Hz, 2H), 2.14 2.05 (m, 2H), 2.01 1.94 (m, 2H), 1.90 1.83 (m, 4H)；13C NMR(151MHz,CDCl3) δ 167.8,138.9,135.7,132.2,131.0,129.1,127.0 (q, J=276.6Hz), 126.1,48.8,45.5,33.1 (q, J=28.6Hz), 31.2,25.9,24.5,22.3 (q, J=2.8Hz)；19F NMR(565MHz,CDCl3)δ–66.2；HRMS(ESI)calcd for C15H18ClF3NO(M+H)+ 320.1029,found 320.1023.
Reaction equation is as follows:
Embodiment 9
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1i, remaining operating procedure is with embodiment 1, productivity: 74%, colourless liquid；1H NMR(600MHz,CDCl3) δ 7.26 7.10 (m, 3H), 3.64 (t, J=7.0Hz, 2H), 3.14 (t, J=6.7Hz, 2H), 2.70 (t, J=7.8Hz, 2H), 2.16 2.06 (m, 2H), 2.00 1.93 (m, 2H), 1.91 1.83 (m, 4H)；13C NMR(151MHz,CDCl3) δ 168.5,139.5,135.8,134.8,129.6,127.6,127.0 (q, J=276.4Hz), 126.7,48.8,45.5,33.2 (q, J=28.6Hz), 31.7,26.0,24.5,22.9 (q, J=2.8Hz)；19F NMR(565MHz,CDCl3)δ–66.1；HRMS(ESI)calcd for C15H18ClF3NO(M+H)+320.1029,found 320.1015.
Reaction equation is as follows:
Embodiment 10
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1j, remaining operating procedure is with embodiment 1, productivity: 72%, colourless liquid；1H NMR(600MHz,CDCl3) δ 7.60 7.51 (m, 3H), 7.49 7.41 (m, 3H), 7.38 7.29 (m, 2H), 3.68 (t, J=7.1Hz, 2H), 3.21 (t, J=6.7Hz, 2H), 2.76 (t, J=7.7Hz, 2H), 2.19 2.09 (m, 2H), 2.02 1.95 (m, 2H), 1.94 1.83 (m, 4H)；13C NMR(151MHz,CDCl3) δ 169.4,140.1,139.5,137.9,136.1,130.0,128.8,127.7, (127.5,127.1 q, J=276.6Hz), 126.9,124.8,48.9,45.5, (33.3 q, J=28.5Hz), 31.5,26.0,24.5,23.1 (q, J=2.8Hz)；19F NMR(565MHz,CDCl3)δ–66.1；HRMS(ESI)calcd for C21H23F3NO(M+H)+362.1732,found 362.1718.
Reaction equation is as follows:
Embodiment 11
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1k, remaining operating procedure is with embodiment 1, productivity: 74%, colourless liquid；1H NMR(600MHz,CDCl3) δ 7.56 7.50 (m, 1H), 7.49 7.42 (m, 3H), 7.30 7.26 (m, 3H), 3.67 (t, J=7.1Hz, 2H), 3.20 (t, J=6.7Hz, 2H), 2.75 (t, J=7.6Hz, 2H), 2.39 (s, 3H), 2.18 2.09 (m, 2H), 2.00 1.95 (m, 2H), 1.92 1.84 (m, 4H)；13C NMR(151MHz,CDCl3) δ 169.4,139.3,137.9,137.3, (137.2,135.7,127.1 q, J=276.6Hz), 123.0,129.5,127.5,126.7,124.5,48.9,45.4,33.3 (q, J=28.4Hz), 31.5,26.0,24.5, (21.0,23.1 q, J=2.8Hz)；19F NMR(565MHz,CDCl3)δ–66.1；HRMS(ESI)calcd for C22H25F3NO(M+H)+376.1888,found 376.1858.
Reaction equation is as follows:
Embodiment 12
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1l, remaining operating procedure is with embodiment 1, productivity: 63%, colourless liquid；1H NMR(600MHz,CDCl3) δ 7.54 7.47 (m, 3H), 7.45 7.39 (m, 1H), 7.31 7.27 (m, 1H), 7.01 6.94 (m, 2H), 3.85 (s, 3H), 3.67 (t, J=7.1Hz, 2H), 3.20 (t, J=6.7Hz, 2H), 2.74 (t, J=7.5Hz, 2H), 2.17 2.08 (m, 2H), 2.01 1.95 (m, 2H), 1.93 1.83 (m, 4H)；13C NMR(151MHz,CDCl3) δ 169.5,159.2,139.0,137.9,135.3,132.5,123.0,127.9, (127.2,127.1 q, J=276.6Hz), 124.3,114.2,55.3,48.9,45.5,33.2 (q, J=28.3Hz), 31.5,26.0, (24.5,23.0 q, J=2.8Hz)；19F NMR(565MHz,CDCl3)δ–66.1；HRMS(ESI)calcd for C22H25F3NO2(M+H)+392.1837,found 392.1815.
Reaction equation is as follows:
Embodiment 13
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1m, remaining operating procedure is with embodiment 1, productivity: 50%, colourless liquid；1H NMR(600MHz,CDCl3) δ 7.59 7.53 (m, 1H), 7.49 7.43 (m, 1H), 7.30 7.24 (m, 3H), 7.11 7.04 (m, 1H), (3.68 t, J=7.1Hz, 2H), 3.20 (t, J=6.7Hz, 2H), 2.72 (t, J=7.7Hz, 2H), 2.17 2.06 (m, 2H), 2.02 1.95 (m, 2H), 1.93 1.84 (m, 4H)；13C NMR(151MHz,CDCl3) δ 169.0,143.3,138.0,136.2,132.8,130.1,128.1,127.1 (q, J=276.6Hz), 126.5,125.0,123.5,123.3,48.8,45.5,33.2 (q, J=28.4Hz), 31.5,26.0,24.5,23.0 (q, J=2.7Hz)；19F NMR(565MHz,CDCl3)δ–66.1；HRMS(ESI)calcd for C19H21F3NOS(M+H)+368.1296,found 368.1280.
Reaction equation is as follows:
Embodiment 14
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1n, remaining operating procedure is with embodiment 1, productivity: 60%, colourless liquid；1H NMR(600MHz,CDCl3) δ 7.43 7.13 (m, 4H), 3.65 (t, J=6.9Hz, 2H), 3.25 3.05 (m, 2H), 2.97 2.85 (m, 1H), 2.19 1.79 (m, 8H), 1.27 (d, J=6.8Hz, 3H)；13C NMR(151MHz,CDCl3) δ 169.4,142.0,137.5,129.4,127.2 (q, J=276.4Hz), 126.4,125.9,125.9,48.9,45.3,34.9,32.0 (q, J=28.4Hz), 29.9,25.9,24.5,22.3；19F NMR(565MHz,CDCl3)δ–66.4；HRMS(ESI)calcd for C16H21F3NO(M+H)+300.1575,found 300.1569.
Reaction equation is as follows:
Embodiment 15
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1o, remaining operating procedure is with embodiment 1, productivity: 65%, colourless liquid；1H NMR(600MHz,CDCl3) δ 7.54 (d, J=7.8Hz, 1H), 7.44 7.39 (m, 1H), 7.32 7.28 (m, 1H), 7.23 (d, J=7.5Hz, 1H), 4.58 4.49 (m, 1H), 3.65 (t, J=7.0Hz, 2H), 3.44 3.38 (m, 1H), 3.35 3.29 (m, 1H), 3.23 3.14 (m, 2H), 2.35 2.15 (m, 2H), 2.03 1.86 (m, 6H), 1.17 (t, J=7.0Hz, 3H)；13C NMR(151MHz,CDCl3) δ 168.7,138.9,136.6,129.3,127.5,127.3 (q, J=276.4Hz), 126.2,125.8,76.3,64.4,49.0,45.4,30.2 (q, J=28.7Hz), 30.2 (q, J=2.7Hz), 26.0,24.5,15.2；19F NMR(565MHz,CDCl3)δ–66.1；HRMS(ESI)calcd for C17H23F3NO2(M+H)+330.1681,found 330.1676.
Reaction equation is as follows:
Embodiment 16
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1p, remaining operating procedure is with embodiment 1, productivity: 63%, white solid, fusing point 48 50 DEG C；1H NMR(600MHz,CDCl3) δ 7.45 7.36 (m, 2H), 7.34 7.29 (m, 1H), 7.26 7.21 (m, 1H), 5.73 (t, J=6.4Hz, 1H), 3.74 3.58 (m, 2H), 3.34 3.16 (m, 2H), 2.33 2.08 (m, 4H), 2.06 (s, 3H), 2.04 1.86 (m, 4H)；13C NMR(151MHz,CDCl3) δ 170.1,168.5,137.3,136.6,129.4,127.9,126.9 (q, J=276.3Hz), 126.0,125.7,72.1,49.0,45.6,30.2 (q, J=29.2Hz), 28.9 (q, J=2.9Hz)；26.0,24.6,21.0；19F NMR(565MHz,CDCl3)δ–66.3；HRMS(ESI)calcd for C17H21F3NO3(M+H)+344.1474,found 344.1469.
Reaction equation is as follows:
Embodiment 17
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1q, remaining operating procedure is with embodiment 1, productivity: 77%, colourless liquid；1H NMR(600MHz,CDCl3) δ 7.33 7.19 (m, 4H), 3.64 (t, J=7.1Hz, 2H), 3.15 (t, J=6.7Hz, 2H), 2.80 2.50 (m, 2H), 2.18 2.08 (m, 2H), 1.98 1.83 (m, 5H), 1.01 (d, J=6.3Hz, 3H)；13C NMR(151MHz,CDCl3) δ 169.4,137.8,136.2,130.4,128.8,127.1 (q, J=276.6Hz), 126.4,126.2,124.3,48.7,45.4,40.2,39.7 (q, J=27.2Hz), 29.2 (q, J=2.3Hz)；25.9,24.5,19.7；19F NMR(565MHz,CDCl3)δ–63.2；HRMS(ESI)calcd for C16H21F3NO(M+H)+300.1575,found 300.1567.
Reaction equation is as follows:
Embodiment 18
Except replacing implementing in example 1 in addition to the 2-allyl benzene formaldehyde shown in structural formula 1a with the 2-allyl benzene benzaldehyde compound shown in structural formula 1r, remaining operating procedure is with embodiment 1, productivity: 60%, colourless liquid；1H NMR(600MHz,CDCl3) δ 7.41 7.29 (m, 2H), 7.26 7.17 (m, 2H), 3.65 (t, J=7.1Hz, 2H), 3.21 3.08 (m, 2H), 2.98 2.86 (dm, 1H), 2.18 1.78 (m, 8H), 1.27 (d, J=6.9Hz, 3H)；13C NMR(151MHz,CDCl3) δ 169.4,142.0,137.5,129.4,127.2 (q, J=276.4Hz), 126.4,125.9,125.9,48.9,45.3,34.9,32.0 (q, J=28.3Hz), 29.9,26.0,24.5,22.3；19F NMR(565MHz,CDCl3)δ–66.4；HRMS(ESI)calcd for C16H21F3NO(M+H)+300.1575,found 300.1571.
Reaction equation is as follows:
Embodiment 19
Except replacing implementing in example 1 in addition to the pyrrolidine shown in structural formula 2a with the aminated compounds shown in 2b, remaining operating procedure is with embodiment 1, productivity: 87%, colourless liquid；1H NMR(600MHz,CDCl3)δ7.33–7.15(m,4H),3.88–3.79(m,1H),3.72–3.61(m,1H),3.24–3.10(m,2H),2.83–2.74(m,1H),2.65–2.55(m,1H),2.18–2.06(m,2H),1.95–1.83(m,2H),1.73–1.61(m,4H),1.54–1.40(m,2H)；13C NMR(151 MHz,CDCl3) δ 169.4,137.3,136.4,129.3,128.9,127.1 (q, J=276.5Hz), 126.4,126.0,48.1,42.4,33.3 (q, J=28.5Hz), 31.7,26.4,25.6,24.5,23.1 (q, J=2.8Hz)；19F NMR(565MHz,CDCl3)δ–66.1；HRMS(ESI)calcd for C16H21F3NO(M+H)+300.1575,found 300.1560.
Reaction equation is as follows:
Embodiment 20
Except replacing implementing in example 1 in addition to the pyrrolidine shown in structural formula 2a with the aminated compounds shown in 2c, remaining operating procedure is with embodiment 1, productivity: 72%, colourless liquid；1H NMR(600MHz,CDCl3)δ7.40–7.30(m,1H),7.28–7.24(m,2H),7.20–7.14(m,1H),3.95–3.67(m,4H),3.65–3.50(m,2H),3.35–3.15(m,2H),2.86–2.73(m,1H),2.67–2.55(m,1H),2.19–2.02(m,2H),1.97–1.80(m,2H)；13C NMR(151MHz,CDCl3) δ 169.7,137.6,135.3,129.6,129.4,127.1 (q, J=276.5Hz), 126.5,126.2,66.9,66.8,47.5,41.9,33.2 (q, J=28.5Hz), 31.8,23.2 (q, J=2.8Hz)；19F NMR(565MHz,CDCl3)δ–66.1；HRMS(ESI)calcd for C15H19F3NO2(M+H)+302.1368,found 302.1361.
Reaction equation is as follows:
Embodiment 21
Except replacing implementing in example 1 in addition to the pyrrolidine shown in structural formula 2a with the aminated compounds shown in 2d, remaining operating procedure is with embodiment 1, productivity: 73%, colourless liquid, fusing point: 147 149 DEG C；1H NMR(600MHz,CDCl3) δ 7.65 7.59 (m, 2H), 7.39 7.30 (m, 3H), 7.25 7.17 (m, 2H), 7.10 7.10 (m, 1H), 4.00 3.80 (m, 2H), 3.41 3.25 (m, 2H), 3.08 (t, J=4.9Hz, 2H), 2.95 2.83 (m, 2H), 2.74 2.61 (m, 1H), 2.51 2.41 (m, 4H), 2.06 1.97 (m, 2H), 1.85 1.71 (m, 18.8Hz, 2H)；13C NMR(151MHz,CDCl3) δ 169.5,144.2,137.6,134.8,132.1,129.8,129.6,129.5, (127.6,126.9 q, J=276.7Hz), 126.5,126.1,46.3,46.1,45.8, (40.7,33.1 q, J=28.6Hz), 31.6, (23.1 q, J=2.8Hz), 21.4；19F NMR(565MHz,CDCl3)δ–66.1；HRMS(ESI)calcd for C22H25F3NO3S(M+H)+455.1616,found 455.1610.
Reaction equation is as follows:
Embodiment 22
Except replacing implementing in example 1 in addition to the pyrrolidine shown in structural formula 2a with the aminated compounds shown in 2e, remaining operating procedure is with embodiment 1, productivity: 75%, colourless liquid；1H NMR(600MHz,CDCl3)δ7.37–7.11(m,14H),5.30–5.00(m,1H),4.36–4.10(m,3H),2.68–2.54(m,2H),2.07–1.76(m,4H)；13C NMR(151MHz,CDCl3) δ 171.5,137.5,136.9,136.0,135.9,129.3,129.2,128.9,128.8,128.7,127.8,127.8, (127.2,127.0 q, J=276.7Hz), 126.5,126.0,51.0,46.5,33.3 (q, J=28.6Hz), 31.8,23.2 (q, J=2.8Hz)；19F NMR(565MHz,CDCl3)δ–66.1；HRMS(ESI)calcd for C15H25F3NO(M+H)+412.1888,found 412.1880.
Reaction equation is as follows:
Embodiment 23
Except replacing implementing in example 1 in addition to the pyrrolidine shown in structural formula 2a with the aminated compounds shown in 2f, remaining operating procedure is with embodiment 1, productivity: 76%, colourless liquid；1H NMR(600MHz,CDCl3) δ 7.34 7.17 (m, 4H), 3.95 3.70 (m, 1H), 3.52 3.28 (m, 1H), 3.11 (q, J=7.1Hz, 2H), 2.81 2.54 (m, 2H), 2.18 2.06 (m, 2H), 1.97 1.83 (m, 2H), 1.26 (t, J=7.1Hz, 3H), 1.05 (t, J=7.1Hz, 3H)；13C NMR(151MHz,CDCl3) δ 170.4,137.0,136.9,129.3,128.8,127.1 (q, J=276.5Hz), 126.3,125.7,42.8,38.6,33.3 (q, J=28.5Hz), 31.7,23.0 (q, J=2.8Hz), 13.9,12.6；19F NMR(565MHz,CDCl3)δ–66.1；HRMS(ESI)calcd for C15H21F3NO(M+H)+288.1575,found 288.1569.
Reaction equation is as follows:
Embodiment 24
Except replacing implementing in example 1 in addition to the pyrrolidine shown in structural formula 2a with the aminated compounds shown in 2g, remaining operating procedure is with embodiment 1, productivity: 57%, colourless liquid；1H NMR(600MHz,CDCl3)δ7.31–7.27(m,1H),7.26–7.16(m,2H),7.12–7.05(m,1H),3.19–3.11(m,1H),3.08–2.97(m,1H),2.81–2.55(m,4H),2.18–2.02(m,2H),1.98–1.78(m,4H),1.75–1.57(m,8H),1.52–.46(m,2H),1.32–1.24(m,3H),1.05–0.87(m,3H)；13C NMR(151MHz,CDCl3) δ 170.5,138.4,136.7,129.2,128.3,127.2 (q, J=276.6Hz), 126.2,124.9,59.7, (56.0,33.4 q, J=28.5Hz), 31.6,31.4,31.2,29.9,29.8,26.7,26.6,25.6,25.5, (25.3,25.1,23.2 q, J=2.8Hz)；19F NMR(565MHz,CDCl3)δ–66.1；HRMS(ESI)calcd for C23H33F3NO(M+H)+396.2514,found 396.2505.
Reaction equation is as follows:
Embodiment 25
Except replacing implementing in example 1 in addition to the pyrrolidine shown in structural formula 2a with the aminated compounds shown in 2h, remaining operating procedure is with embodiment 1, productivity: 56%, colourless liquid；1H NMR(600MHz,CDCl3) δ 7.32 7.27 (m, 1H), 7.25 7.19 (m, 2H), 7.08 7.15 (m, 1H), 3.70 3.62 (m, 1H), 3.55 3.46 (m, 1H), 2.78 2.59 (m, 2H), 2.17 2.07 (m, 2H), 1.99 1.85 (m, 2H), 1.61 1.52 (m, 6H), 1.10 (d, J=6.7Hz, 6H)；13C NMR(151MHz,CDCl3) δ 170.2,138.3,136.9,129.2,128.4,127.2 (q, J=276.6Hz), (126.3,125.0,50.7,45.8,33.4 q, J=28.4Hz), 31.7, (23.2 q, J=2.7Hz), 20.7,20.7,20.5,20.4；.19F NMR(565MHz,CDCl3)δ–66.0；HRMS(ESI)calcd for C17H25F3NO(M+H)+316.1888, found 316.1881. reaction equation is as follows:
Embodiment 26
Except replacing implementing in example 1 in addition to the pyrrolidine shown in structural formula 2a with the aminated compounds shown in 2i, remaining operating procedure is with embodiment 1, productivity: 84%, colourless liquid；1H NMR(600MHz,CDCl3)δ7.41–7.19(m,8H),7.13–7.10(m,1H),5.10–4.50(m,2H),2.78–2.56(m,5H),2.18–2.01(m,2H),1.97–1.80(m,2H)；13C NMR(151MHz,CDCl3) δ 171.0,137.5,137.2,136.9,129.4,129.0,128.7, (128.4,127.6,127.0 q, J=276.6Hz), 126.5,126.1,50.2, (36.1,33.3 q, J=28.5Hz), 31.7,23.1 (q, J=2.8Hz)；19F NMR(565MHz,CDCl3)δ–66.1；HRMS(ESI)calcd for C16H21F3NO(M+H)+336.1575,found336.1565.
Reaction equation is as follows:
Embodiment 27
Except replacing implementing in example 1 in addition to the pyrrolidine shown in structural formula 2a with the aminated compounds shown in 2j, remaining operating procedure is with embodiment 1, productivity: 82%, colourless liquid；1H NMR(600MHz,CDCl3) δ 7.34 7.29 (m, 1H), 7.26 7.21 (m, 2H), 7.19 7.13 (m, 1H), 3.74 3.35 (m 2H), 2.79 (s, 3H), 2.75 2.43 (m, 2H), 1.97 1.84 (m, 4H), 1.68 1.60 (m, 2H), 1.44 1.37 (m, 2H), 0.99 (t, J=7.4Hz, 3H)；13C NMR(151MHz,CDCl3) δ 170.7,137.0,136.8,129.4,128.8,127.1 (q, J=276.6Hz), 126.4,126.1,46.6,36.6,33.2 (q, J=28.5Hz), 31.7,29.0,23.0 (q, J=2.7Hz), 20.1,13.8；19F NMR(565MHz,CDCl3)δ–66.2；HRMS(ESI)calcd for C16H23F3NO(M+H)+302.1732,found 302.1729.
Reaction equation is as follows:
。
Claims (4)
1. the preparation method of ε-trifluoromethyl substituted amide, it is characterised in that comprise the steps:
Copper catalyst, alkali and the togni reagent shown in structure formula III are dissolved in organic solvent, adds shown in structure formula II
2-allyl benzene benzaldehyde compound and pyrrolidine form reaction system, and reaction system is at room temperature reacted 10 hours, post-treated
Obtain the ε shown in structural formula I-trifluoromethyl substituted amide；
In formula I and formula II, R1For hydrogen atom, methyl, methoxyl group, methylene-dioxy, fluorine atom, chlorine atom, phenyl, right
Tolyl, p-methoxyphenyl or thienyl.
Method the most according to claim 1, it is characterised in that: described copper catalyst, alkali, togni reagent, structure
The mol ratio of the compound shown in formula II and pyrrolidine is 0.1:1.5:1.5:1:1.5.
Method the most according to claim 1, it is characterised in that described copper catalyst is copper sulfate, described alkali is carbon
Acid potassium, described organic solvent is DMF.
Method the most according to claim 1, it is characterised in that described post processing include cancellation, extract, be dried and post
Chromatography.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610341590.3A CN106008402B (en) | 2016-05-23 | 2016-05-23 | A kind of ε-trifluoromethyl substituted amide preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201610341590.3A CN106008402B (en) | 2016-05-23 | 2016-05-23 | A kind of ε-trifluoromethyl substituted amide preparation method |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106810430A (en) * | 2016-11-30 | 2017-06-09 | 浙江师范大学 | A kind of preparation method of the naphthoquinone derivatives of 2 trifluoromethyl 1,4 |
| CN106977386A (en) * | 2017-04-05 | 2017-07-25 | 浙江师范大学 | A kind of indone of 2 trifluoroethyl 1 and its derivative and preparation method |
| CN111592444A (en) * | 2020-06-08 | 2020-08-28 | 浙江师范大学 | (Z) -5-fluoro-2-trifluoromethyl olefin derivative and preparation method thereof |
| CN115650874A (en) * | 2022-10-27 | 2023-01-31 | 西南大学 | Method for synthesizing o-phenylenediamine compounds |
-
2016
- 2016-05-23 CN CN201610341590.3A patent/CN106008402B/en active Active
Non-Patent Citations (4)
| Title |
|---|
| CUNGUI CHENG ET AL.: "Copper-Catalyzed Trifluoromethylation of Alkenes with Redox-Neutral Remote Amidation of Aldehydes", 《ORG. LETT.》 * |
| PENG YU ET AL.: "Enantioselective C-H Bond Functionalization Triggered by Radical Trifluoromethylation of Unactivated Alkene", 《ANGEW. CHEM. INT. ED.》 * |
| 王兮等: "经由三氟甲基自由基的三氟甲基化反应研究进展", 《中国科学》 * |
| 王兮等: "铜催化的利用高价碘试剂的(sp3-sp3)碳碳键生成反应：一种有效的烯丙位三氟甲基化反应", 《第五届全国大学生创新创业年会》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106810430A (en) * | 2016-11-30 | 2017-06-09 | 浙江师范大学 | A kind of preparation method of the naphthoquinone derivatives of 2 trifluoromethyl 1,4 |
| CN106810430B (en) * | 2016-11-30 | 2019-07-30 | 浙江师范大学 | A kind of 2- Trifluoromethyl-1, the preparation method of 4- naphthoquinone derivatives |
| CN106977386A (en) * | 2017-04-05 | 2017-07-25 | 浙江师范大学 | A kind of indone of 2 trifluoroethyl 1 and its derivative and preparation method |
| CN106977386B (en) * | 2017-04-05 | 2020-09-01 | 浙江师范大学 | 2-trifluoroethyl-1-indanone and derivatives and preparation method thereof |
| CN111592444A (en) * | 2020-06-08 | 2020-08-28 | 浙江师范大学 | (Z) -5-fluoro-2-trifluoromethyl olefin derivative and preparation method thereof |
| CN115650874A (en) * | 2022-10-27 | 2023-01-31 | 西南大学 | Method for synthesizing o-phenylenediamine compounds |
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| CN106008402B (en) | 2018-06-26 |
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