CN107011195B - A method of passing through catalysis oxidation one-step synthesis a-amino acid esters compound - Google Patents
A method of passing through catalysis oxidation one-step synthesis a-amino acid esters compound Download PDFInfo
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- CN107011195B CN107011195B CN201710207481.7A CN201710207481A CN107011195B CN 107011195 B CN107011195 B CN 107011195B CN 201710207481 A CN201710207481 A CN 201710207481A CN 107011195 B CN107011195 B CN 107011195B
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- China
- Prior art keywords
- amino acid
- acid esters
- esters compound
- step synthesis
- catalysis oxidation
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- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 25
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 24
- 238000000034 method Methods 0.000 title claims abstract description 21
- 238000006555 catalytic reaction Methods 0.000 title claims abstract description 15
- 230000003647 oxidation Effects 0.000 title claims abstract description 14
- 238000007254 oxidation reaction Methods 0.000 title claims abstract description 14
- -1 alkene ether/aminated compounds Chemical class 0.000 claims abstract description 52
- 238000006243 chemical reaction Methods 0.000 claims abstract description 36
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 230000001590 oxidative effect Effects 0.000 claims abstract description 11
- 239000007800 oxidant agent Substances 0.000 claims abstract description 10
- 239000000126 substance Substances 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- 230000000694 effects Effects 0.000 claims abstract description 5
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 39
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 33
- 239000000047 product Substances 0.000 claims description 28
- 239000003208 petroleum Substances 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 8
- 238000004440 column chromatography Methods 0.000 claims description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N tert-butyl alcohol Substances CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 3
- 235000019441 ethanol Nutrition 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- 229910002666 PdCl2 Inorganic materials 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- YQHLDYVWEZKEOX-UHFFFAOYSA-N cumene hydroperoxide Chemical compound OOC(C)(C)C1=CC=CC=C1 YQHLDYVWEZKEOX-UHFFFAOYSA-N 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- VTIIJXUACCWYHX-UHFFFAOYSA-L disodium;carboxylatooxy carbonate Chemical compound [Na+].[Na+].[O-]C(=O)OOC([O-])=O VTIIJXUACCWYHX-UHFFFAOYSA-L 0.000 claims description 2
- 235000013305 food Nutrition 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- YTZKOQUCBOVLHL-UHFFFAOYSA-N p-methylisopropylbenzene Natural products CC(C)(C)C1=CC=CC=C1 YTZKOQUCBOVLHL-UHFFFAOYSA-N 0.000 claims description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical group Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 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
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims description 2
- 235000019394 potassium persulphate Nutrition 0.000 claims description 2
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims description 2
- 239000012264 purified product Substances 0.000 claims description 2
- 229940045872 sodium percarbonate Drugs 0.000 claims description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims 2
- 125000004924 2-naphthylethyl group Chemical group C1=C(C=CC2=CC=CC=C12)CC* 0.000 claims 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims 1
- 239000005977 Ethylene Substances 0.000 claims 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims 1
- 239000004202 carbamide Substances 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 150000004040 pyrrolidinones Chemical class 0.000 claims 1
- 239000000758 substrate Substances 0.000 abstract description 7
- 239000002994 raw material Substances 0.000 abstract description 6
- 150000002978 peroxides Chemical class 0.000 abstract description 3
- 125000000524 functional group Chemical group 0.000 abstract description 2
- 231100000252 nontoxic Toxicity 0.000 abstract description 2
- 230000003000 nontoxic effect Effects 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 32
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 26
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 22
- FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 description 20
- 229910052763 palladium Inorganic materials 0.000 description 17
- 238000003756 stirring Methods 0.000 description 15
- 239000012043 crude product Substances 0.000 description 14
- 238000010438 heat treatment Methods 0.000 description 14
- 238000005292 vacuum distillation Methods 0.000 description 14
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 238000007445 Chromatographic isolation Methods 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 238000011097 chromatography purification Methods 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 239000011734 sodium Substances 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 238000010189 synthetic method Methods 0.000 description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 229910052802 copper Inorganic materials 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 150000004982 aromatic amines Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- PPTXVXKCQZKFBN-UHFFFAOYSA-N (S)-(-)-1,1'-Bi-2-naphthol Chemical class C1=CC=C2C(C3=C4C=CC=CC4=CC=C3O)=C(O)C=CC2=C1 PPTXVXKCQZKFBN-UHFFFAOYSA-N 0.000 description 1
- GLCCHGVDZXCRGD-UHFFFAOYSA-N 1-ethenyl-2-ethylnaphthalene Chemical compound C1=CC=CC2=C(C=C)C(CC)=CC=C21 GLCCHGVDZXCRGD-UHFFFAOYSA-N 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical class [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- 102000010726 Glycine Plasma Membrane Transport Proteins Human genes 0.000 description 1
- 108010063380 Glycine Plasma Membrane Transport Proteins Proteins 0.000 description 1
- 206010054949 Metaplasia Diseases 0.000 description 1
- 241000239226 Scorpiones Species 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 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
- 238000012925 biological evaluation Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical class [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 1
- VGIYPVFBQRUBDD-UHFFFAOYSA-N ethenoxycyclohexane Chemical compound C=COC1CCCCC1 VGIYPVFBQRUBDD-UHFFFAOYSA-N 0.000 description 1
- AZDCYKCDXXPQIK-UHFFFAOYSA-N ethenoxymethylbenzene Chemical compound C=COCC1=CC=CC=C1 AZDCYKCDXXPQIK-UHFFFAOYSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000015689 metaplastic ossification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 229910017464 nitrogen compound Inorganic materials 0.000 description 1
- 150000002830 nitrogen compounds Chemical class 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 150000002896 organic halogen compounds Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910000144 sodium(I) superoxide Inorganic materials 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical group CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/12—Formation of amino and carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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 ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
- C07D215/06—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical fields of organic chemical industry, disclose a kind of method by catalysis oxidation one-step synthesis a-amino acid esters compound.The method, comprising the following steps: (1) react the collective effect that alkene ether/aminated compounds or acrylamide compound and aminated compounds pass through catalyst and oxidant in organic solvent；(2) after having reacted, product is isolated and purified, obtains a-amino acid esters compound.The method safe operation is simple, one-step synthesis, obtains ester bond during reaction, makees oxidant using nontoxic and pollution-free peroxide, low in raw material price is easy to get, good to functional group adaptability, to substrate wide adaptability, it is environmental-friendly, there is good prospects for commercial application.
Description
Technical field
The present invention relates to medicine, organic chemical industry's synthesis technical field, and in particular to is closed to a kind of by one step of catalysis oxidation
At the method for a-amino acid esters compound.
Background technique
Amino acid is the basic unit for constituting protein molecule in vivo, is had with the vital movement of biology close
Relationship.It has special physiological function in antibody, is one of indispensable nutritional ingredient in organism.Since it is in life
The important application of object pharmaceutically, efficiently synthesizes the extensive concern for having obtained chemists.However due to the particularity of its structure,
In synthesis or some are limited, but are hydrolyzed by the synthesis of amino-acid ester, then in a mild condition, so that it may obtain corresponding amino
Acid derivative, therefore this method compensates for the deficiency directly synthesized, provides new method and thinking for diversity synthesis.
A-amino acid (glycine) is a kind of neurotransmitter element, the inhibition and excitement of neurotransmitter in central nervous system
On play an important role, derivative is also also to be found to have good bioactivity, such as antibacterial agent
(C.L.Cioffi,S.Liu,M.A.Wolf,P.R.Guzzo,K.Sadalapure,V.Par thasarathy,
D.T.J.Loong et al.J.Med.Chem.2016,59,8473,M.A.T.Bla skovich,Synthesis and
Biological Evaluation of N-((1-(4-(Sulfonyl)piperazin-1-yl)cycloalkyl)methyl)
benzamide Inhibitors of Glycine Transporter-1,J.Med.Ch em.,2016,59(24),
10807)。
OxfenicineIt is used as promoting the medicine of the oxidation of carbohydrate in myocardial infarction in clinic
Object, drugIt is a kind of anti-glycine swivel agent.
In recent years, synthesis chemist has developed the effective ways of some building alpha-amido acid compounds.Someone
(M.E.Morilla,M.M.Diaz-Requejo,T.R.Belderrain,M.C.Nicasio,S.Trofimenlco,
P.J.Perez,Catalytic insertion of diazo compounds into N–H bonds:the copper
Alternative, Chem.Commun., 2002,2998.) using the copper catalyst of itself scorpion type coordination, by amine and diazonium class
It closes object catalysis and generates α-aminoacidesters, but the reaction can be carried out reaction only for fatty amine, arylamine class substrate not can be carried out instead
It answers, and substrate adaptive is poor.Teacher Feng little Ming seminar (Z.R.Hou, J.Wang, P.He, J.Wang, B.Qin, X.H.Liu, L,
L,Lin,X.M.Feng.Highly Enantioselective Insertion of Carbenoids into N-H Bonds
Catalyzed by Copper(I)Complexes of Binol Derivatives.Angew.Chem.Int.Ed.,2010,
49,4763.) to copper catalytic amine and diazonium class compound synthesis α-aminoacidesters carried out deeper into research, not only realize
Breakthrough to arylamine class substrate also realizes its asymmetric syntheses for the first time.But also there is also some disadvantages for the reaction simultaneously, such as anti-
Used heavy nitrogen compound is by ester and TsN in answering3What class compound synthesis came out, the ester of α-aminoacidesters is to pass through
What substrate was seen in, rather than construct during the reaction.
In the prior art, most common method is that the halides of ester are obtained amino acid esters chemical combination by ammonia nucleophilic attack
Object.This kind of synthetic method needs to use the organohalogen compounds of chemical dose, and starting halo ester needs are previously prepared, and its
Body is exactly a kind of raw material being not readily available.Therefore develop simply and easily, and more multifarious α-aminoacidesters can be synthesized
The synthetic method of class compound seems more important.
Summary of the invention
In order to overcome the defect and deficiency of existing synthesis a-amino acid esters compound, the present invention provides one kind by urging
Change the method for oxidative synthesis a-amino acid esters compound.The present invention is using basic chemical raw materials as the substrate of reaction, palladium chemical combination
Object is catalyst, and peroxide serves not only as Green Oxidant, the also source as oxygen in α-aminoacidesters, and a step constructs C-N,
C-O key obtains α-aminoacidesters.And the operation is easy, low in raw material price, Atom economy is high, reaction condition temperature
With, it is pollution-free, it is environmental-friendly the features such as.Synthetic method before relatively shows apparent advantage.
The purpose of the present invention is achieved through the following technical solutions:
A method of passing through catalysis oxidation one-step synthesis a-amino acid esters compound, comprising the following steps:
(1) alkene ether/aminated compounds or acrylamide compound and aminated compounds are passed through into catalysis in organic solvent
The collective effect of agent and oxidant is reacted；
(2) after having reacted, product is isolated and purified, obtains a-amino acid esters compound.
The structural formula of the alkene ether/aminated compounds are as follows:X is O or N；The acrylamide compound is N-
Vinylamide class compound, preferably n-vinyl pyrrolidone；
The aminated compounds is that tetrahydroquinoline, tetrahydroisoquinoline, tetrahydro -1H- benzo [b] azatropylidene or structural formula areCompound；
Wherein R1For phenyl, 2- aminomethyl phenyl, 3- aminomethyl phenyl, 4- aminomethyl phenyl, to ethylphenyl, p-fluorophenyl is right
Chlorphenyl, p-bromophenyl, p-isopropyl phenyl or to Phenoxyphenyl；
R2For hydrogen, methyl, ethyl, isopropyl, allyl or propionitrile base；
R3For ethyl, benzyl, cyclohexyl, phenethyl, 2- naphthylethylTo tert-butyl benzene ethyl, Buddha's warrior attendant
Alkyl, p-fluorophenyl, 2- chloroethyl or 2- trifluoromethyl ethyl.
The reaction is carried out under air conditions.
The molar ratio of the alkene ether/aminated compounds or acrylamide compound and aminated compounds is 1~3:1.
The catalyst is PdCl2, Pd (OAc)2, Pd (PPh3)Cl2, Pd (PhCN)2Cl2, Pd (MeCN)2Cl2, Pd
(dba)2, Pd (PPh3)4One of.
The molar ratio of the oxidant and aminated compounds is 2~10:1.
The oxidant is TBHP (70%aq.) (tert-Butanol peroxide), DTBP (di-t-butyl peroxide), H2O2(35%
Aq.) (hydrogen peroxide), cumyl hydroperoxide, SODIUM PERCARBONATE, hydrogen peroxide urea, tert-Butanol peroxide, the tertiary fourth of peroxidating two
Base, one kind of potassium peroxydisulfate.
The organic solvent is dimethyl sulfoxide, n,N-Dimethylformamide, toluene or Isosorbide-5-Nitrae-dioxane, acetonitrile, N,
One of N- dimethyl acetamide or ethyl alcohol.
The temperature of the reaction is 40~100 DEG C.
The time of the reaction is 1~12 hour.
It is described after reaction to be isolated and purified product using column chromatography；The column chromatographic eluate is pure hexane or stone
The mixed solvent of oily ether and ethyl acetate, petroleum ether and ethyl acetate volume ratio are 10~50:1.
Above-mentioned reaction equation is as follows:
The reaction equation of alkene ether compound or olefinic amine compound and aminated compounds is as follows:
Reacting for acrylamide compound and aminated compounds is also in this way, direct with amido bond in acrylamide compound
The carbon-carbon double bond of connection, is oxidized to CH2C=O contains N-CH in the structure of amino acid esters compound at this time2C (O)-N, it is left
The N on side is the nitrogen of aminated compounds amino, and the N on the right is the nitrogen in acrylamide compound in amido bond.
The amino acid esters compound is mainly used in the fields such as chemical industry, medicine, food, agricultural.
Obtained α-aminoacidesters are the major class in weight polyamino acid esters in the present invention, are had very important potential
Application value.
The principle of the present invention be using aminated compounds and alkene ether/aminated compounds or acrylamide compound as raw material,
Under palladium chtalyst, the product that intermolecular nucleophilic palladium metaplasia is hydroxylated at amine occurs, then is oxidized and generates a-amino acid esters compound.
The present invention compared with the prior art, has the following advantages that and effect:
Simple (the one-step synthesis, in the process of reaction of the synthetic method safe operation of a-amino acid esters compound of the present invention
In obtain ester bond), make oxidant using nontoxic and pollution-free peroxide, low in raw material price is easy to get, suitable to functional group
Answering property is good, environmental-friendly to substrate wide adaptability, has good prospects for commercial application.
Detailed description of the invention
Fig. 1 is the hydrogen spectrogram of 7 gained a-amino acid esters compound of embodiment；
Fig. 2 is the carbon spectrogram of 7 gained a-amino acid esters compound of embodiment；
Fig. 3 is the hydrogen spectrogram of 8 gained a-amino acid esters compound of embodiment；
Fig. 4 is the carbon spectrogram of 8 gained a-amino acid esters compound of embodiment；
Fig. 5 is the hydrogen spectrogram of 9 gained a-amino acid esters compound of embodiment；
Fig. 6 is the carbon spectrogram of 9 gained a-amino acid esters compound of embodiment；
Fig. 7 is the hydrogen spectrogram of 10 gained a-amino acid esters compound of embodiment；
Fig. 8 is the carbon spectrogram of 10 gained a-amino acid esters compound of embodiment；
Fig. 9 is the hydrogen spectrogram of 11 gained a-amino acid esters compound of embodiment；
Figure 10 is the carbon spectrogram of 11 gained a-amino acid esters compound of embodiment；
Figure 11 is the hydrogen spectrogram of 12 gained a-amino acid esters compound of embodiment；
Figure 12 is the carbon spectrogram of 12 gained a-amino acid esters compound of embodiment；
Figure 13 is the hydrogen spectrogram of 13 gained a-amino acid esters compound of embodiment；
Figure 14 is the carbon spectrogram of 13 gained a-amino acid esters compound of embodiment；
Figure 15 is the hydrogen spectrogram of 14 gained a-amino acid esters compound of embodiment；
Figure 16 is the carbon spectrogram of 14 gained a-amino acid esters compound of embodiment.
Specific embodiment
The present invention is described in further detail with attached drawing combined with specific embodiments below, but embodiments of the present invention
It is without being limited thereto.
Embodiment 1
0.25 mM of methylphenylamine, 0.5 mM of vinyl ethyl ether, opposite methylphenylamine are added in reaction flask
The 5mol%Pd (OAc) of dosage2, 1 mM of hydrogen peroxide, 1 milliliter of n,N-Dimethylformamide, under air conditions, 40 DEG C are stirred
After mixing reaction 12 hours, stops heating and stirring, be cooled to room temperature, vacuum distillation obtains crude product, then passes through column chromatography for separation
Purifying obtains a-amino acid esters compound i.e. target product, and column chromatographic eluate used is petroleum ether: ethyl acetate=
20:1 (volume ratio), yield 32%.
Embodiment 2
0.25 mM of methylphenylamine, 0.5 mM of vinyl ethyl ether, opposite methylphenylamine are added in reaction flask
The 5mol%Pd (OAc) of dosage2, 1 mM of hydrogen peroxide, 1 milliliter of n,N-Dimethylformamide, under air conditions, 100 DEG C are stirred
After mixing reaction 12 hours, stops heating and stirring, be cooled to room temperature, vacuum distillation obtains crude product, then passes through column chromatography for separation
Purifying obtains a-amino acid esters compound i.e. target product, and column chromatographic eluate used is petroleum ether: ethyl acetate=
20:1 (volume ratio), yield 44%.
Embodiment 3
0.25 mM of methylphenylamine, 0.5 mM of vinyl ethyl ether, opposite methylphenylamine are added in reaction flask
The 5mol%Pd (OAc) of dosage2, 1 mM of hydrogen peroxide, 1 milliliter of Isosorbide-5-Nitrae-dioxane, under air conditions, 60 DEG C of stirrings are anti-
After answering 12 hours, stopping heating and stirring, be cooled to room temperature, vacuum distillation obtains crude product, then passes through column chromatographic isolation and purification,
A-amino acid esters compound i.e. target product is obtained, column chromatographic eluate used is petroleum ether: ethyl acetate=20:1 (body
Product ratio), yield 61%.
Embodiment 4
0.25 mM of methylphenylamine, 0.5 mM of vinyl ethyl ether, opposite methylphenylamine are added in reaction flask
The 5mol%Pd (OAc) of dosage2, 1 mM of hydrogen peroxide, 1 milliliter of n,N-dimethylacetamide, under air conditions, 60 DEG C are stirred
After mixing reaction 12 hours, stops heating and stirring, be cooled to room temperature, vacuum distillation obtains crude product, then passes through column chromatography for separation
Purifying obtains a-amino acid esters compound i.e. target product, and column chromatographic eluate used is petroleum ether: ethyl acetate=
20:1 (volume ratio), yield 74%.
Embodiment 5
0.25 mM of methylphenylamine, 0.5 mM of vinyl ethyl ether, opposite methylphenylamine are added in reaction flask
The 5mol%Pd (OAc) of dosage2, 1 mM of hydrogen peroxide, 1 milliliter of ethyl alcohol, under air conditions, 60 DEG C are stirred to react 12 hours
Afterwards, stop heating and stirring, be cooled to room temperature, vacuum distillation obtains crude product, then by column chromatographic isolation and purification, obtains α-ammonia
Base acid esters compound, that is, target product, column chromatographic eluate used are petroleum ether: ethyl acetate=20:1 (volume ratio), are produced
Rate 68%.
Embodiment 6
0.25 mM of methylphenylamine, 0.5 mM of vinyl ethyl ether, opposite methylphenylamine are added in reaction flask
The 5mol%Pd (OAc) of dosage2, 1 mM of hydrogen peroxide, 1 milliliter of n,N-Dimethylformamide, under inert gas shielding, 60
After DEG C being stirred to react 12 hours, stop heating and stirring, be cooled to room temperature, vacuum distillation obtains crude product, then passes through column chromatography
It isolates and purifies, obtains a-amino acid esters compound i.e. target product, column chromatographic eluate used is petroleum ether: ethyl acetate
=20:1 (volume ratio), yield 5%.
Embodiment 7
0.25 mM of methylphenylamine, 0.5 mM of vinyl ethyl ether, opposite methylphenylamine are added in reaction flask
The 5mol%Pd (OAc) of dosage2, 1 mM of hydrogen peroxide, 1 milliliter of n,N-Dimethylformamide, under air conditions, 60 DEG C are stirred
After mixing reaction 12 hours, stops heating and stirring, be cooled to room temperature, vacuum distillation obtains crude product, then passes through column chromatography for separation
Purifying obtains a-amino acid esters compound i.e. target product, and column chromatographic eluate used is petroleum ether: ethyl acetate=
20:1 (volume ratio), yield 81%.
The structural characterization data of embodiment 1-7 products therefrom are as follows:
IR(KBr):2921,2856,1737,1603,1503,1371,1191,1109,1032,749cm-1.
1H NMR(400MHz,CDCl3): δ 7.25-7.20 (m, 2H), 6.74 (t, J=7.3Hz, 1H), 6.69 (d, J=
8.0Hz, 2H), 4.17 (q, J=7.1Hz, 2H), 4.05 (s, 2H), 3.06 (s, 3H), 1.23 (t, J=7.1Hz, 3H)
13C NMR(100MHz,CDCl3):δ171.0,148.9,129.2,117.3,112.3,60.9,54.6,39.5,
14.2.
HRMS-ESI(m/z):C11H15NNaO2,[M+Na]+: 216.0995, actual measurement: 216.0993.
Infer that the structure of products therefrom is as follows according to above data:
Embodiment 8
0.25 mM is added in reaction flask to methyl N-methylaniline, relatively to methyl N-methylaniline dosage
5mol%Pd (OAc)2, 0.5 mM of vinyl ethyl ether, 1 mM of hydrogen peroxide, 1 milliliter of n,N-Dimethylformamide, air
Under the conditions of, after 60 DEG C are stirred to react 12 hours, stopping heating and stirring, be cooled to room temperature, vacuum distillation obtains crude product, then
By column chromatographic isolation and purification, a-amino acid esters compound i.e. target product is obtained, column chromatographic eluate used is petroleum
Ether: ethyl acetate=20:1, yield 79%.
The structural characterization data of 8 products therefrom of embodiment are as follows:
IR(KBr):2922,2858,1740,1688,1620,1519,1458,1388,1190,1112,1031,804,
750cm-1.
1H NMR(400MHz,CDCl3): δ 7.07 (d, J=8.5Hz, 2H), 6.65 (d, J=8.5Hz, 2H), 4.19 (q, J
=7.1Hz, 2H), 4.05 (s, 2H), 3.07 (s, 3H), 2.27 (s, 3H), 1.27 (t, J=7.1Hz, 3H)
13C NMR(100MHz,CDCl3):δ171.2,146.9,129.7,126.5,112.6,60.8,54.8,39.6,
20.3,14.2.
HRMS-ESI(m/z):C12H17NNaO2,[M+Na]+: 230.1151, actual measurement: 230.1152.
Infer that the structure of products therefrom is as follows according to above data:
Embodiment 9
The 5mol%Pd (OAc) of 0.25 mM of aniline, opposite aniline dosage is added in reaction flask2, 0.5 mM of second
Under air conditions, it is small to be stirred to react 12 at 60 DEG C for vinyl ethyl ether, 1 mM of hydrogen peroxide, 1 milliliter of n,N-Dimethylformamide
Shi Hou stops heating and stirring, is cooled to room temperature, and vacuum distillation obtains crude product, then by column chromatographic isolation and purification, obtains α-
Amino acid esters compound, that is, target product, column chromatographic eluate used are petroleum ether: ethyl acetate=20:1, yield
60%.
IR (KBr): 3053,2979,2919,2852,1733,1606,1513,1446,1281,1208,1119,1024,
744,694cm-1.
1H NMR(400MHz,CDCl3): δ 7.19 (t, J=7.8Hz, 2H), 6.75 (t, J=7.3Hz, 1H), 6.61 (d, J
=8.2Hz, 2H), 4.25 (q, J=7.1Hz, 2H), 3.90 (s, 2H), 1.30 (t, J=7.1Hz, 3H)
13C NMR(100MHz,CDCl3):δ171.2,147.0,129.3,118.1,113.0,77.4,77.0,76.7,
61.3,45.9,14.2.
HRMS-ESI(m/z):C10H14NO2,[M+H]+: 180.1019, actual measurement: 180.1015.
Infer that the structure of products therefrom is as follows according to above data:
Embodiment 10
The 5mol%Pd (OAc) of 0.25 mM of tetrahydroquinoline, opposite tetrahydroquinoline dosage is added in reaction flask2, 0.5
MM vinyl ethyl ether, 1 mM of hydrogen peroxide, 1 milliliter of n,N-Dimethylformamide under air conditions, are stirred at 60 DEG C
After reaction 12 hours, stop heating and stirring, be cooled to room temperature, vacuum distillation obtains crude product, then pure by column chromatography for separation
Change, obtain a-amino acid esters compound i.e. target product, column chromatographic eluate used is petroleum ether: ethyl acetate=20:
1, yield 69%.
IR(KBr):2923,2855,1740,1636,1502,1458,1379,1265,1179,1098,752cm-1.
1H NMR(400MHz,CDCl3): δ 7.02 (t, J=7.8Hz, 1H), 6.97 (d, J=7.3Hz, 1H), 6.62 (t, J
=7.3Hz, 1H), 6.42 (d, J=8.2Hz, 1H), 4.19 (q, J=7.1Hz, 2H), 4.00 (s, 2H), 3.41 (t, J=
7.0Hz, 2H), 2.80 (t, J=6.3Hz, 2H), 2.04-1.97 (m, 2H), 1.26 (t, J=7.1Hz, 3H)
13C NMR(101MHz,CDCl3):δ171.1,144.8,129.2,127.1,122.8,116.8,110.3,60.8,
53.2,50.6,27.9,22.3,14.3.
HRMS-ESI(m/z):C13H17NNaO2,[M+Na]+: 242.1151, actual measurement: 242.1145.
Infer that the structure of products therefrom is as follows according to above data:
Embodiment 11
The 5mol%Pd of 0.25 mM of methylphenylamine, opposite methylphenylamine dosage is added in reaction flask
(OAc)2, 0.5 mM of vinyl cyclohexyl ether, 1 mM of hydrogen peroxide, 1 milliliter of n,N-Dimethylformamide, air conditions
Under, after 60 DEG C are stirred to react 12 hours, stop heating and stirring, be cooled to room temperature, vacuum distillation obtains crude product, then passes through
Column chromatographic isolation and purification, obtains a-amino acid esters compound i.e. target product, and column chromatographic eluate used is petroleum ether: second
Acetoacetic ester volume ratio=20:1, yield 80%.
IR(KBr):2929,2857,1730,1608,1505,1452,1366,1189,1116,749cm-1.
1H NMR(400MHz,CDCl3):δ7.26–7.21(m,2H),6.76–6.69(m,3H),4.87–4.79(m,1H),
4.05(s,2H),3.08(s,3H),1.79–1.75(m,2H),1.65–1.62(m,2H),1.48–1.23(m,6H).
13C NMR(100MHz,CDCl3):δ170.6,149.0,129.1,117.3,112.4,73.2,54.9,39.6,
31.5,25.3,23.4.
HRMS-ESI(m/z):C15H22NO2,[M+H]+: 248.1645, actual measurement: 248.1649.
Infer that the structure of products therefrom is as follows according to above data:
Embodiment 12
The 5mol%Pd of 0.25 mM of methylphenylamine, opposite methylphenylamine dosage is added in reaction flask
(OAc)2, 0.5 mM of vinyl benzyl ether, 1 mM of hydrogen peroxide, 1 milliliter of n,N-Dimethylformamide, air conditions
Under, after 60 DEG C are stirred to react 12 hours, stop heating and stirring, be cooled to room temperature.Vacuum distillation obtains crude product, then passes through
Column chromatographic isolation and purification, obtains a-amino acid esters compound i.e. target product, and column chromatographic eluate used is petroleum ether: second
Acetoacetic ester volume ratio=20:1, yield 78%.
IR(KBr):2922,2856,1742,1603,1505,1457,1367,1179,1118,747,695cm-1.
1H NMR(400MHz,CDCl3): δ 7.33-7.31 (m, 2H), 7.27-7.20 (m, 4H), 6.75 (t, J=7.3Hz,
1H), 6.69 (d, J=7.9Hz, 2H), 5.15 (s, 2H), 4.11 (s, 2H), 3.06 (s, 3H)
13C NMR(100MHz,CDCl3):δ170.9,148.8,135.6,129.2,128.6,128.3,128.2,
117.8,112.4,66.6,54.6,39.6.
HRMS-ESI(m/z):C16H17NNaO2,[M+Na]+: 278.1151, actual measurement: 278.1149.
Infer that the structure of products therefrom is as follows according to above data:
Embodiment 13
The 5mol%Pd of 0.25 mM of methylphenylamine, opposite methylphenylamine dosage is added in reaction flask
(OAc)2, 0.5 mM of n-vinyl pyrrolidone, 1 mM of hydrogen peroxide, 1 milliliter of n,N-Dimethylformamide, air item
Under part, after 60 DEG C are stirred to react 12 hours, stop heating and stirring, be cooled to room temperature.Vacuum distillation obtains crude product, then leads to
Column chromatographic isolation and purification is crossed, a-amino acid esters compound i.e. target product is obtained, column chromatographic eluate used is petroleum ether:
Ethyl acetate volume ratio=20:1, yield 65%.
IR(KBr):2892,2857,1736,1698,1603,1509,1367,1254,1118,1027,749cm-1.
1H NMR(400MHz,CDCl3) δ 7.21 (t, J=7.2Hz, 2H), 6.74-6.65 (m, 3H), 4.68 (s, 2H),
3.81 (t, J=6.9Hz, 2H), 3.05 (s, 3H), 2.63 (t, J=7.8Hz, 2H), 2.13-2.05 (m, 2H)
13C NMR(100MHz,CDCl3)δ176.1,171.5,149.1,129.1,117.1,112.2,57.4,45.1,
39.4,33.3,17.7.
HRMS-ESI(m/z):C13H16N2NaO2,[M+Na]+: 255.1104, actual measurement: 255.1108.
Infer that the structure of products therefrom is as follows according to above data:
Embodiment 14
The 5mol%Pd of 0.25 mM of methylphenylamine, opposite methylphenylamine dosage is added in reaction flask
(OAc)2, 0.5 mM of vinyl -2-ethylnaphthalene ether, 1 mM of hydrogen peroxide, 1 milliliter of n,N-Dimethylformamide, air
Under the conditions of, after 60 DEG C are stirred to react 12 hours, stop heating and stirring, be cooled to room temperature.Vacuum distillation obtains crude product, then
By column chromatographic isolation and purification, a-amino acid esters compound i.e. target product is obtained, column chromatographic eluate used is petroleum
Ether: ethyl acetate volume ratio=20:1, yield 64%.
IR(KBr):2924,2854,1731,1638,1506,1378,1266,1104,751cm-1.
1H NMR(400MHz,CDCl3): δ 8.04 (d, J=8.2Hz, 1H), 7.85 (d, J=7.9Hz, 1H), 7.74 (d, J
=8.2Hz, 1H), 7.53-7.45 (m, 2H), 7.37 (t, J=7.6Hz, 1H), 7.28 (d, J=7.0Hz, 1H), 7.24-7.19
(m, 2H), 6.74 (t, J=7.2Hz, 1H), 6.64 (d, J=8.0Hz, 2H), 4.46 (t, J=7.2Hz, 2H), 4.02 (s,
2H), 3.37 (t, J=7.2Hz, 2H), 2.99 (s, 3H)
13C NMR(100MHz,CDCl3):δ171.1,148.8,133.9,133.5,132.0,129.2,128.9,
127.5,127.1,126.2,125.7,125.5,123.5,117.4,112.3,64.8,54.5,39.5,32.2.
HRMS-ESI(m/z):C21H21NNaO2,[M+Na]+: 342.1464, actual measurement: 342.1462.
Infer that the structure of products therefrom is as follows according to above data:
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not limited by examples detailed above
System, others are any to be without departing from made changes, modifications, substitutions, combinations, simplifications under spirit of the invention and principle
Effect.
Claims (8)
1. a kind of method by catalysis oxidation one-step synthesis a-amino acid esters compound, it is characterised in that including following step
It is rapid:
(1) by alkene ether/aminated compounds or acrylamide compound and aminated compounds pass through in organic solvent catalyst and
The collective effect of oxidant is reacted；
(2) after having reacted, product is isolated and purified, obtains a-amino acid esters compound；
The structural formula of the alkene ether/aminated compounds are as follows:X is O or N；The acrylamide compound is N- ethylene
Base pyrrolidones；
The aminated compounds is that tetrahydroquinoline, tetrahydroisoquinoline, tetrahydro -1H- benzo [b] azatropylidene or structural formula areCompound；
Wherein R1For phenyl, 2- aminomethyl phenyl, 3- aminomethyl phenyl, 4- aminomethyl phenyl, to ethylphenyl, p-fluorophenyl, to chlorobenzene
Base, p-bromophenyl, p-isopropyl phenyl or to Phenoxyphenyl；
R2For hydrogen, methyl, ethyl, isopropyl, allyl or propionitrile base；
R3For ethyl, benzyl, cyclohexyl, phenethyl, 2- naphthylethyl, to tert-butyl benzene ethyl, adamantyl, p-fluorophenyl, 2- chlorine
Ethyl or 2- trifluoromethyl ethyl；
The catalyst is PdCl2, Pd (OAc)2, Pd (PPh3)Cl2, Pd (PhCN)2Cl2, Pd (MeCN)2Cl2, Pd (dba)2, Pd
(PPh3)4One of；
The oxidant is tert-Butanol peroxide, di-t-butyl peroxide, hydrogen peroxide, cumyl hydroperoxide, SODIUM PERCARBONATE, mistake
Aoxidize urea hydrogen, tert-Butanol peroxide, di-t-butyl peroxide, one of potassium peroxydisulfate.
2. passing through the method for catalysis oxidation one-step synthesis a-amino acid esters compound according to claim 1, feature exists
In: the organic solvent be dimethyl sulfoxide, n,N-Dimethylformamide, toluene or Isosorbide-5-Nitrae-dioxane, acetonitrile, N, N- diformazan
One of yl acetamide or ethyl alcohol.
3. passing through the method for catalysis oxidation one-step synthesis a-amino acid esters compound according to claim 1, feature exists
In: the molar ratio of the alkene ether/aminated compounds or acrylamide compound and aminated compounds is 1~3:1；
The molar ratio of the oxidant and aminated compounds is 2~10:1.
4. passing through the method for catalysis oxidation one-step synthesis a-amino acid esters compound according to claim 1, feature exists
In: the temperature of the reaction is 40~100 DEG C；The time of the reaction is 1~12 hour.
5. passing through the method for catalysis oxidation one-step synthesis a-amino acid esters compound according to claim 1, feature exists
In: the reaction is carried out under air conditions.
6. passing through the method for catalysis oxidation one-step synthesis a-amino acid esters compound according to claim 1, feature exists
In: described reacted afterwards is isolated and purified product using column chromatography；The column chromatographic eluate be pure hexane or petroleum ether and
The mixed solvent of ethyl acetate.
7. passing through the method for catalysis oxidation one-step synthesis a-amino acid esters compound according to claim 6, feature exists
In: petroleum ether and ethyl acetate volume ratio be 10~50:1.
8. passing through the method for catalysis oxidation one-step synthesis a-amino acid esters compound according to claim 1, feature exists
In: the a-amino acid esters compound is applied to chemical industry, medicine, food, agriculture field.
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