CN117567226A - Synthesis method of alpha-amino acid compound - Google Patents
Synthesis method of alpha-amino acid compound Download PDFInfo
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- CN117567226A CN117567226A CN202311526265.0A CN202311526265A CN117567226A CN 117567226 A CN117567226 A CN 117567226A CN 202311526265 A CN202311526265 A CN 202311526265A CN 117567226 A CN117567226 A CN 117567226A
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- amino acid
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- acid compound
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- imine
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- -1 alpha-amino acid compound Chemical class 0.000 title claims abstract description 61
- 235000008206 alpha-amino acids Nutrition 0.000 title claims abstract description 58
- 238000001308 synthesis method Methods 0.000 title claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- 239000011941 photocatalyst Substances 0.000 claims abstract description 19
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000000654 additive Substances 0.000 claims abstract description 15
- 230000000996 additive effect Effects 0.000 claims abstract description 15
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 239000012298 atmosphere Substances 0.000 claims abstract description 8
- 230000032050 esterification Effects 0.000 claims abstract description 6
- 238000005886 esterification reaction Methods 0.000 claims abstract description 6
- 230000001681 protective effect Effects 0.000 claims abstract description 6
- 238000005286 illumination Methods 0.000 claims abstract description 4
- 150000002466 imines Chemical class 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 17
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 11
- 238000003786 synthesis reaction Methods 0.000 claims description 10
- GCGRXVMGBHYMDA-UHFFFAOYSA-N 5-fluoro-2,4,6-tris(N-phenylanilino)benzene-1,3-dicarbonitrile Chemical compound C1(=CC=CC=C1)N(C1=C(C#N)C(=C(C(=C1C#N)N(C1=CC=CC=C1)C1=CC=CC=C1)F)N(C1=CC=CC=C1)C1=CC=CC=C1)C1=CC=CC=C1 GCGRXVMGBHYMDA-UHFFFAOYSA-N 0.000 claims description 8
- 230000002194 synthesizing effect Effects 0.000 claims description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- BITDLWAQPKSXTF-UHFFFAOYSA-M 1-[(3-nitrophenyl)methoxymethyl]pyridin-1-ium;chloride Chemical compound [Cl-].[O-][N+](=O)C1=CC=CC(COC[N+]=2C=CC=CC=2)=C1 BITDLWAQPKSXTF-UHFFFAOYSA-M 0.000 claims description 2
- ZOMQCVKHGOMNER-UHFFFAOYSA-N 2,4,5,6-tetrakis(N-phenylanilino)benzene-1,3-dicarbonitrile Chemical compound C(#N)C1=C(C(=C(C(=C1N(C1=CC=CC=C1)C1=CC=CC=C1)N(C1=CC=CC=C1)C1=CC=CC=C1)N(C1=CC=CC=C1)C1=CC=CC=C1)C#N)N(C1=CC=CC=C1)C1=CC=CC=C1 ZOMQCVKHGOMNER-UHFFFAOYSA-N 0.000 claims description 2
- VQGHOUODWALEFC-UHFFFAOYSA-N 2-phenylpyridine Chemical compound C1=CC=CC=C1C1=CC=CC=N1 VQGHOUODWALEFC-UHFFFAOYSA-N 0.000 claims description 2
- TXNLQUKVUJITMX-UHFFFAOYSA-N 4-tert-butyl-2-(4-tert-butylpyridin-2-yl)pyridine Chemical compound CC(C)(C)C1=CC=NC(C=2N=CC=C(C=2)C(C)(C)C)=C1 TXNLQUKVUJITMX-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- ZBQZBWKNGDEDOA-UHFFFAOYSA-N eosin B Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC([N+]([O-])=O)=C(O)C(Br)=C1OC1=C2C=C([N+]([O-])=O)C(O)=C1Br ZBQZBWKNGDEDOA-UHFFFAOYSA-N 0.000 claims description 2
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 229960002581 moroxydine hydrochloride Drugs 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 239000000758 substrate Substances 0.000 abstract description 7
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 239000000203 mixture Substances 0.000 abstract description 5
- 239000003638 chemical reducing agent Substances 0.000 abstract description 4
- 230000006698 induction Effects 0.000 abstract description 2
- 238000012512 characterization method Methods 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 6
- 230000008569 process Effects 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 150000001371 alpha-amino acids Chemical class 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 239000001569 carbon dioxide Substances 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- 238000007059 Strecker synthesis reaction Methods 0.000 description 2
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 230000001678 irradiating effect Effects 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 150000003891 oxalate salts Chemical class 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 238000005086 pumping Methods 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- SAPGTCDSBGMXCD-UHFFFAOYSA-N (2-chlorophenyl)-(4-fluorophenyl)-pyrimidin-5-ylmethanol Chemical compound C=1N=CN=CC=1C(C=1C(=CC=CC=1)Cl)(O)C1=CC=C(F)C=C1 SAPGTCDSBGMXCD-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 150000001723 carbon free-radicals Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000005518 electrochemistry Effects 0.000 description 1
- VEGXETMJINRLTH-ALRICIOSSA-N etimicin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@H](O)[C@H]1O[C@@H]1[C@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N VEGXETMJINRLTH-ALRICIOSSA-N 0.000 description 1
- 229950009953 etimicin Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 208000007386 hepatic encephalopathy Diseases 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229960004502 levodopa Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000011112 process operation Methods 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
- 239000002516 radical scavenger Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B41/00—Formation or introduction of functional groups containing oxygen
- C07B41/12—Formation or introduction of functional groups containing oxygen of carboxylic acid ester groups
-
- 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
- C07C227/02—Formation of carboxyl groups in compounds containing amino groups, e.g. by oxidation of amino alcohols
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- 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
- C07D333/26—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 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
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthesis method of an alpha-amino acid compound. The synthesis method comprises the following steps: in a protective atmosphere, the mixture contains iminesAnd carrying out illumination reaction on a mixed reaction system of the compound, the photocatalyst, the oxalate, the additive and the solvent, and then carrying out esterification treatment to obtain the alpha-amino acid compound. The synthesis method of the alpha-amino acid compound provided by the invention does not need CO 2 Under the induction of visible light, oxalate is used as a reducing agent and a C1 source to efficiently synthesize the alpha-amino acid compound; meanwhile, the synthesis method has mild reaction conditions, wide selectivity of reaction substrates, capability of being amplified to gram scale, basically unaffected yield and good industrial application prospect.
Description
Technical Field
The invention belongs to the technical field of organic chemical synthesis, and particularly relates to a synthesis method of an alpha-amino acid compound.
Background
Amino acids are important constituent fragments of proteins and play an indispensable role in organisms. Alpha-amino acids are widely found in many natural products and bioactive compounds and play an important role in biochemistry, pharmaceutical science, material science, and synthetic organic chemistry. To date, many drug structures have been reported to contain α -amino acids, such as levodopa for the treatment of parkinson's disease, azoserine for the treatment of acute leukemia and Huo Jinsen, etimicin as a broad-spectrum antibiotic, arginine for the treatment of hepatic encephalopathy, glutamine for the treatment of digestive tract diseases, and the like. In the field of organic synthesis, alpha-amino acids can be used as starting materials for synthesizing a variety of biologically active compounds, and can play an important ligand role in catalytic reactions involving transition metals. Therefore, the method for synthesizing the alpha-amino acid derivative has very important scientific significance and application value, and the adoption of a mild and efficient method is one of the hot spots in the current organic synthesis field.
The imine refers to an organic compound containing C=N double bonds, and is widely applied to the fields of medicines, organic synthesis and the like. Can be prepared by condensing commercial ammonia with corresponding aldehyde and ketone. Because of their simple and readily available nature, imine compounds are one of the commonly used substrates for the synthesis of alpha-amino acids.
In the past, the method for synthesizing alpha-amino acid by utilizing imine mainly adopts the methods of Strecker reaction, electrochemistry and photochemistry. Highly toxic cyanide is used in the Strecker reaction, and the reaction needs to be carried out under strong acid, high temperature and high pressure conditions. Electrochemical has the defects of using a sacrificial anode and being difficult to operate. In photochemical processes, substrate universality is difficult to ensure. As same asWhen the method is used, carbon dioxide gas is required to be introduced, and the operation is inconvenient. Thus, a method of producing a non-CO gas 2 Under the gas condition, the mild and efficient synthesis of the alpha-amino acid compound under the reaction condition is a problem to be solved urgently.
Disclosure of Invention
The invention mainly aims to provide a synthesis method of an alpha-amino acid compound, which aims to overcome the defects of the prior art.
In order to achieve the purpose of the invention, the technical scheme adopted by the invention comprises the following steps:
the embodiment of the invention provides a synthesis method of an alpha-amino acid compound, which comprises the following steps:
in a protective atmosphere, a mixed reaction system comprising an imine compound, a photocatalyst, an oxalate, an additive and a solvent is subjected to an illumination reaction, and then is subjected to esterification treatment to obtain the alpha-amino acid compound.
In some more specific embodiments, the imine compound includes a carbonyl-containing imine and/or an aryl imine.
Compared with the prior art, the invention has the beneficial effects that: the synthesis method of the alpha-amino acid compound provided by the invention does not need CO 2 Under the induction of visible light, oxalate is used as a reducing agent and a C1 source to efficiently synthesize the alpha-amino acid compound; meanwhile, the synthetic method has mild reaction conditions and wide selectivity of reaction substrates, can be amplified to gram scale, and basically has no influence on yield; in addition, the invention overcomes the defects of high toxicity and harsh reaction conditions of the reagents in the prior art, and has good industrial application prospect.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required to be used in the embodiments or the description of the prior art will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments described in the present invention, and other drawings may be obtained according to the drawings without inventive effort to those skilled in the art.
FIG. 1 is a schematic illustration of the mechanism of synthesis of an alpha-amino acid compound in an exemplary embodiment of the invention.
Detailed Description
In view of the shortcomings of the prior art, the inventor of the present application has long studied and put forward a great deal of practice, and the technical solution of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Specifically, as one aspect of the technical scheme of the invention, the synthesis method of the alpha-amino acid compound comprises the following steps: in a protective atmosphere, a mixed reaction system comprising an imine compound, a photocatalyst, an oxalate, an additive and a solvent is subjected to an illumination reaction, and then is subjected to esterification treatment to obtain the alpha-amino acid compound.
In some preferred embodiments, the imine compound includes a carbonyl-containing imine and/or an aryl imine.
Further, the carbonyl-containing imine has a structure as shown in formula (I):
wherein Ar is 1 、Ar 2 、Ar 3 Independently selected from aryl groups containing halogen atoms, ester groups, cyano groups, alkyl groups, or alkoxy groups.
In some preferred embodiments, the aryl imine has a structure as shown in formula (II):
wherein Ar is 4 、Ar 5 、Ar 6 Independent and independentIs selected from aryl groups.
In some preferred embodiments, the photocatalyst comprises 4DPAIPN, ir (ppy) 3 、Ir[df(CF 3 )ppy] 2 (dtppy)PF 6 、[Ir(dtbbpy)(ppy) 2 ]PF 6 Any one or a combination of two or more of 3DPAFIPN, eosin Y and Eosin B.
Further, the photocatalyst is 3DPAFIPN.
In some preferred embodiments, the oxalate salt comprises Na 2 C 2 O 4 、SrC 2 O 4 、H 2 C 2 O 4 、[N(CH 3 ) 4 ] 2 C 2 O 4 、[N(CH 2 CH 3 ) 4 ] 2 C 2 O 4 、[N(nBu) 4 ] 2 C 2 O 4 Any one or a combination of two or more of them, and is not limited thereto.
Further, the oxalate salt is [ N (nBu) 4 ] 2 C 2 O 4 。
In some preferred embodiments, the additive includes any one or a combination of two or more of TMG, 2-t-butyl-1, 3-tetramethylguanidine, moroxydine hydrochloride, and is not limited thereto.
Further, the additive is TMG.
In some preferred embodiments, the solvent includes any one or a combination of two or more of DMF, DMA, DMSO, NMP, meCN, 1,4-dioxane, meOH, and is not limited thereto.
Further, the solvent is DMF.
In some preferred embodiments, the molar ratio of the imine compound, photocatalyst, oxalate, and additive is 1:0.01-0.02:0.9-2:0.6-2.
Further, the molar ratio of the imine compound to the photocatalyst to the oxalate to the additive is 1:0.02:1.2:1.1.
In some preferred embodiments, the synthetic method specifically comprises: and (3) placing the imine compound, the photocatalyst, the oxalate and the additive into a reaction container, adding a solvent under a protective atmosphere, and stirring at room temperature under the condition of visible light irradiation for reacting for 2-12 h to obtain the alpha-amino acid compound.
Further, the wavelength of the visible light is 400-550 nm.
In the invention, the visible light with the wavelength of 400-550 nm is used for irradiating the reactant in the reaction process, the light in the wavelength range is blue light, the energy of the blue light is lower, only the photocatalyst is acted, the light in the wavelength range is easier to be absorbed by the photocatalyst, the photocatalyst can be activated efficiently, and the reaction efficiency is improved; in addition, blue light can not be absorbed by organic compounds, so that the decomposition of the compounds can not be caused, and the high yield of the synthesis reaction is ensured.
Further, the synthesis method further comprises: after the reaction is completed, methyl iodide is added into the obtained reaction system for esterification treatment, and then separation and purification are carried out.
In some preferred embodiments, the method of synthesizing the α -amino acid compound comprises:
adding imine compound, photocatalyst, oxalate and additive in the ratio of 1 to 0.01-0.02 to 0.9-2 to 0.6-2 into reaction container, and then adding the mixture into N 2 Adding a solvent under the atmosphere, stirring at room temperature for reaction for 5 hours, and irradiating the reaction solution with visible light with the wavelength of 400-550 nm in the reaction process; then, after-treatment is carried out by methyl iodide, and then, the mixture after the reaction is separated and purified to obtain the alpha-amino acid compound.
In some more specific embodiments, the method of synthesizing the α -amino acid compound comprises:
(1) To a dried Schlenk tube (5 mL) containing magnetons was added 0.2mmol of the reaction substrate (imine compound), 0.004mmol of the photocatalyst (2 mol%);
(2) The Schlenk tube was transferred into a glove box, and 0.24mmol of oxalate (1.2 equiv) was charged into the Schlenk tube;
(3) After closing the Schlenk tube, the tube was taken out of the glove box and connected to a tube containing N 2 Double row pipe of steel cylinderUnscrewing the cap and pumping the charge N on the double gauntlet 2 At least 3 times;
(4) To be filled with N 2 0.22mmol of additive (e.g., TMG) (1.1 equiv), 2mL of solvent (e.g., DMF) was added to the Schlenk tube;
(5) The Schlenk tube containing the reaction solution was placed at a distance of 45w from a blue LED lamp (wavelength of about 450 nm) Stirring at room temperature (about 25 ℃) for reaction for 5 hours;
(6) After the imine is completely converted, adding CH into a reaction system 3 I (8 equiv), stirring at room temperature for 4h;
(7) After the reaction was completed, water (30 mL) and ethyl acetate (3×30 mL) were added to the system to extract, and the mixture was concentrated and dried by spin-drying in a rotary evaporator, and the residue was purified by flash column chromatography under the following conditions: petroleum ether/ethyl acetate=10/1-5/1 is used to obtain pure product (alpha-amino acid compound).
The technical scheme of the present invention is further described in detail below with reference to several preferred embodiments and the accompanying drawings, and the embodiments are implemented on the premise of the technical scheme of the present invention, and detailed implementation manners and specific operation processes are given, but the protection scope of the present invention is not limited to the following embodiments.
The experimental materials used in the examples described below, unless otherwise specified, were all commercially available from conventional biochemicals.
Example 1
The method of the α -amino acid compound of this example comprises the steps of:
(1) To a dried Schlenk tube (5 mL) containing magnetons was added 0.2mmol of the reaction substrate (imine-based compound), 0.004mmol of the photocatalyst 3DPAFIPN (2 mol%);
(2) The Schlenk tube was transferred into a glove box and 0.24mmol of oxalate [ N (nBu) was charged into the Schlenk tube 4 ] 2 C 2 O 4 (1.2equiv)；
(3) After closing the Schlenk tube, the tube was taken out of the glove box and connected to a tube containing N 2 On the double row pipes of the steel bottle, unscrewing the cover and pumping and charging N on the double row pipes 2 At least 3 times;
(4) To be filled with N 2 0.22mmol of additive TMG (1.1 equiv) and 2mL of DMF were added to the Schlenk tube;
(5) The Schlenk tube containing the reaction solution was placed at a distance of 45W from a blue LED lamp (wavelength of about 450 nm) Stirring at room temperature (about 25 ℃) for reaction for 5 hours;
(6) After the imine is completely converted, adding CH into a reaction system 3 I (8 equiv), stirring at room temperature for 4h;
(7) After the reaction was completed, water (30 mL) and ethyl acetate (3×30 mL) were added to the system to extract, and the mixture was concentrated and dried by spin-drying in a rotary evaporator, and the residue was purified by flash column chromatography under the following conditions: petroleum ether/ethyl acetate=10/1-5/1 is used to obtain pure product (alpha-amino acid compound).
The reaction formula in this example is shown below:
the imine compound and the corresponding alpha-amino acid compound product and yield used in this example are shown below:
wherein the product alpha-amino acid compound isAt 99% yield, the characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.92(s，1H)，7.84(d，J＝8.0Hz，2H)，7.46(dp，J＝15.2，7.2Hz，7H)，7.32(q，J＝8.0，7.2Hz，6H)，3.78(s，3H).
13 C NMR(100MHz，CDCl 3 )δ172.9，165.5，138.9，134.5，131.9，128.7(2)，128.6(6)，128.1，128.0，127.3，70.2，53.7.
ESIHRMS：m/z Calcd.For C 22 H 19 NO 3 ：(M+Na) + 368.1257.Found：368.1253.
the product alpha-amino acid compound isAt 87% yield, characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.82(s，1H)，7.60(dd，J＝3.6，1.2Hz，1H)，7.52-7.42(m，5H)，7.38-7.29(m，6H)，7.08(dd，J＝4.8，3.6Hz，1H)，3.78(s，3H).
13 C NMR(100MHz，CDCl 3 )δ172.9，160.1，139.2，138.6，130.5，128.7(0)，128.6(5)，128.1(4)，128.1(0)，127.8，70.3，53.8.
ESIHRMS：m/z Calcd.For C 20 H 17 NO 3 S：(M-H) + 350.0856.Found：350.0851.
the product alpha-amino acid compound isAt 67% yield, the characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.25(ddt，J＝8.8，5.2，2.8Hz，12H)，7.17(dd，J＝5.2，3.2Hz，2H)，7.05(s，1H)，3.70(t，J＝2.0Hz，3H)，2.92(t，J＝7.2Hz，2H)，2.57(tt，J＝7.2，1.6Hz，2H).
13 C NMR(100MHz，CDCl 3 )δ172.5，170.4，140.8，138.9，128.7，128.6，128.5，128.0，127.9，126.3，69.9，53.5，38.4，31.2.
ESIHRMS：m/z Calcd.For C 24 H 23 NO 3 ：(M+Na) + 396.1570.Found：396.1570.
the product alpha-amino acid compound isAt 55% yield, characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.53(dd，J＝7.6，1.6Hz，4H)，7.39-7.32(m，6H)，7.12(s，1H)，6.80(s，2H)，3.77(s，3H)，2.26(s，3H)，2.17(s，6H).
13 C NMR(100MHz，CDCl 3 )δ172.1，168.8，139.3，138.7，134.9，134.2，128.8，128.5，128.1，128.0，70.0，53.4，21.2，19.2.
ESIHRMS：m/z Calcd.For C 25 H 25 NO 3 ：(M+Na) + 410.1727.Found：410.1720.
the product alpha-amino acid compound isAt 94% yield, characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ8.01(s，1H)，7.94-7.89(m，2H)，7.67-7.62(m，2H)，7.59(dd，J＝7.2，1.2Hz，2H)，7.51-7.42(m，6H)，7.39-7.29(m，7H)，3.78(s，3H).
13 C NMR(100MHz，CDCl 3 )δ172.9，165.2，144.7，140.0，138.8，132.9，129.0，128.7，128.1，128.0，127.8，127.3(4)，127.3(0)，70.2，53.7.
ESIHRMS：m/z Calcd.For C 28 H 23 NO 3 ：(M+Na) + 444.157.Found：444.1561.
the product alpha-amino acid compound isAt 83% yield, characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.93(s，1H)，7.84(dd，J＝8.0，5.6Hz，2H)，7.46(d，J＝7.2Hz，4H)，7.33(q，J＝6.8，6.4Hz，6H)，7.09(t，J＝8.4Hz，2H)，3.78(s，3H).
13 C NMR(100MHz，CDCl 3 )δ173.0，164.9(d，J＝250.8Hz)，164.4，138.6，130.5(d，J＝2.7Hz)，129.6(d，J＝8.9Hz)，128.6，128.1(3)，128.1(0)，115.7(d，J＝21.7Hz)，70.2，53.8.
19 F NMR(376MHz，CDCl 3 )δ-107.6.
ESIHRMS：m/z Calcd.For C 22 H 18 FNO 3 ：(M-H) + 362.1198.Found：362.1192.
the product alpha-amino acid compound isAt 93% yield, characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.90(s，1H)，7.74(d，J＝8.0Hz，2H)，7.50-7.43(m，4H)，7.36-7.27(m，6H)，7.22(d，J＝8.0Hz，2H)，3.77(s，3H)，2.38(s，3H).
13 C NMR(100MHz，CDCl 3 )δ172.9，165.5，142.3，138.9，131.5，129.3，128.6，128.1，128.0，127.2，70.1，53.7，21.6.
ESIHRMS：m/z Calcd.For C 23 H 21 NO 3 ：(M+Na) + 382.1414.Found：382.1411.
the product alpha-amino acid compound isThe yield was 95% and the characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.84(s，1H)，7.82-7.78(m，2H)，7.48-7.44(m，4H)，7.35-7.27(m，6H)，6.94-6.88(m，2H)，3.82(s，3H)，3.77(s，3H).
13 C NMR(100MHz，CDCl 3 )δ173.0，165.1，162.5，139.0，129.1，128.6，128.1，127.9，126.6，113.8，70.1，55.5，53.7.
ESIHRMS：m/z Calcd.For C 23 H 21 NO 4 ：(M+Na) + 398.1363.Found：398.1365.
the product alpha-amino acid compound isAt 90% yield, the characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.90(s，1H)，7.79-7.74(m，2H)，7.49-7.44(m，4H)，7.36-7.27(m，6H)，7.25-7.22(m，2H)，3.78(s，3H)，2.66-2.58(m，2H)，1.68-1.60(m，2H)，0.93(t，J＝7.2Hz，3H).
13 C NMR(100MHz，CDCl 3 )δ172.9，165.5，147.0，138.9，131.7，128.8，128.6，128.1，128.0，127.3，70.1，53.7，37.9，24.4，13.8.
ESIHRMS：m/z Calcd.For C 25 H 25 NO 3 ：(M+Na) + 410.1727.Found：410.1724.
the product alpha-amino acid compound isAt 82% yield, characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ8.36(s，1H)，8.12(s，1H)，7.92-7.82(m，4H)，7.57-7.48(m，6H)，7.38-7.29(m，6H)，3.80(s，3H).
13 C NMR(100MHz，CDCl 3 )δ173.0，165.6，138.8，134.9，132.7，131.5，129.1，128.8，128.7，128.6，128.1(4)，128.0(6)，127.9，127.8，126.9，123.7，70.3，53.8.
ESIHRMS：m/z Calcd.For C 26 H 21 NO 3 ：(M+Na) + 418.1414.Found：418.1404.
the product alpha-amino acid compound isAt 91% yield, characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.37-7.27(m，10H)，3.74(s，3H)，1.23(s，9H).
13 C NMR(100MHz，CDCl 3 )δ176.6，172.7，139.3，128.3，128.0，127.8，69.4，53.5，39.1，27.5.
ESIHRMS：m/z Calcd.For C 20 H 23 NO 3 ：(M+Na) + 348.157.Found：348.1568.
the product alpha-amino acid compound isAt 99% yield, the characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.99(s，1H)，7.91-7.77(m，2H)，7.57-7.34(m，7H)，7.08-6.98(m，2H)，6.94-6.83(m，2H)，3.80(d，J＝0.8Hz，6H).
13 C NMR(100MHz，CDCl 3 )δ173.0，165.5，162.2(d，J FC ＝246.2Hz)，159.3，134.6(d，J FC ＝3.1Hz)，134.3，131.9，130.7，130.6，129.8，128.7，127.2，114.8(d，J F c＝21.4Hz)，113.6，69.2，55.4，53.8.
19 F NMR(376MHz，CDCl 3 )δ-114.7.
ESIHRMS：m/z Calcd.For C 23 H 20 FNO 4 ：(M+Na) + 416.1269.Found：416.1266.
the product alpha-amino acid compound isAt 99% yield, the characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.90(s，1H)，7.87-7.79(m，2H)，7.53-7.38(m，5H)，7.37-7.18(m，6H)，7.12(d，J＝6.4Hz，1H)，3.78(s，3H)，2.32(s，3H).
13 C NMR(100MHz，CDCl 3 )δ173.0，165.5，138.9，138.8，137.8，134.5，131.9，129.1，128.9，128.7，128.1，128.0，127.3，125.7，70.1，53.7，21.8.
ESIHRMS：m/z Calcd.For C 23 H 21 NO 3 ：(M+Na) + 328.1414.Found：328.1417.
the product alpha-amino acid compound isAt 93% yield, characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.96(s，1H)，7.84(dq，J＝6.4，1.6Hz，2H)，7.51-7.30(m，7H)，7.19-7.08(m，4H)，3.76(s，3H)，2.33(s，6H).
13 C NMR(100MHz，CDCl 3 )δ173.2，165.4，137.7，135.9，134.5，131.8，128.8，128.6，128.5，127.2，69.8，53.7，21.2.
ESIHRMS：m/z Calcd.For C 24 H 23 NO 3 ：(M+Na) + 396.1570.Found：396.1561.
the product alpha-amino acid compound isYield was 85% and characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ8.03(s，1H)，7.86-7.80(m，2H)，7.56-7.50(m，1H)，7.48-7.39(m，6H)，7.09-6.98(m，4H)，3.80(s，3H).
13 C NMR(100MHz，CDCl 3 )δ172.8，165.4，162.4(d，J FC ＝246.8Hz)，134.2，134.0，132.1，130.5(d，J FC ＝8.1Hz)，128.8，127.2，115.1(d，J FC ＝21.5Hz)，69.2，54.0.
19 F NMR(376MHz，CDCl 3 )δ-114.4.
ESIHRMS：m/z Calcd.For C 22 H 17 F 2 NO 3 ：(M+Na) + 404.1069.Found：404.1057.
the product alpha-amino acid compound isAt 83% yield, characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ8.18(s，1H)，7.85(dt，J＝6.8，1.6Hz，2H)，7.61-7.26(m，10H)，7.15-6.97(m，2H)，3.79(s，3H).
13 C NMR(100MHz，CDCl 3 )δ172.7，165.4，160.8(d，J FC ＝245.6Hz)，135.1，134.4，133.1(d，J FC ＝2.8Hz)，131.9，130.1(d，J FC ＝8.9Hz)，128.7，128.4，128.4，128.2，127.6(d，J FC ＝10.8Hz)，127.3，123.0(d，J FC ＝3.1Hz)，115.4(d，J FC ＝22.0Hz)，66.7，54.0.
19 F NMR(376MHz，CDCl 3 )δ-114.3.
ESIHRMS：m/z Calcd.For C 22 H 18 FNO 3 ：(M+Na) + 386.1163.Found：386.1155.
the product alpha-amino acid compound isAt 88% yield, characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.92(s，1H)，7.70-7.58(m，2H)，7.53-7.42(m，4H)，7.39-7.24(m，8H)，3.78(s，3H)，2.38(s，3H).
13 C NMR(100MHz，CDCl 3 )δ173.0，165.7，138.9，138.6，134.3，132.6，128.7，128.6，128.1，128.0，124.2，70.2，53.7，21.5.
ESIHRMS：m/z Calcd.For C 23 H 21 NO 3 ：(M+Na) + 382.1414.Found：382.1412.
the product alpha-amino acid compound isAt 94% yield, characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ8.16-8.00(m，3H)，7.96-7.80(m，2H)，7.53-7.40(m，4H)，7.40-7.26(m，6H)，3.93(s，3H)，3.80(s，3H).
13 C NMR(100MHz，CDCl 3 )δ172.9，166.4，164.6，138.4，138.3，133.0，130.0，128.7，128.2，127.3，70.4，53.9，52.5.
ESIHRMS：m/z Calcd.For C 24 H 21 NO 5 ：(M+Na) + 426.1312.Found：426.1305.
the product alpha-amino acid compound isYield was 69% and the characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ8.08(s，1H)，7.98-7.86(m，2H)，7.78-7.65(m，2H)，7.51-7.41(m，4H)，7.39-7.31(m，6H)，3.80(s，3H).
13 C NMR(100MHz，CDCl 3 )δ172.9，163.6，138.3，138.0，132.6，128.7，128.3，128.2，128.0，118.1，115.4，70.4，54.0.
ESIHRMS：m/z Calcd.For C 23 H 18 N 2 O 3 ：(M+Na) + 393.1210.Found：393.1201.
the product alpha-amino acid compound isAt 59% yield, characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.41-7.19(m，11H)，3.75(s，3H)，1.53(dddd，J＝11.2，8.0，4.0，1.6Hz，1H)，0.88(tq，J＝8.4，3.6，2.4Hz，2H)，0.71(ddt，J＝10.8，4.4，2.0Hz，2H).
13 C NMR(100MHz，CDCl 3 )δ172.6，171.9，139.4，128.5，128.0，127.8，69.9，53.5，15.2，7.2.
ESIHRMS：m/z Calcd.For C 19 H 19 NO 3 ：(M+Na) + 332.1257.Found：332.1262.
the product alpha-amino acid compound isAt 91% yield, characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.97(s，1H)，7.89-7.79(m，2H)，7.54-7.39(m，7H)，7.38-7.29(m，3H)，7.05-6.96(m，2H)，3.79(s，3H).
13 C NMR(100MHz，CDCl 3 )δ172.8，165.5，162.3(d，J FC ＝246.2Hz)，138.6，134.4(d，J FC ＝3.2Hz)，134.2，132.0，130.7(d，J FC ＝6.5Hz)，128.8，128.5，128.2(9)，128.2(5)，127.2，114.9(d，J FC ＝21.4Hz)，69.7，53.8.
19 F NMR(376MHz，CDCl 3 )δ-114.8.
ESIHRMS：m/z Calcd.For C 22 H 18 FNO 3 ：(M+Na) + 386.1163.Found：386.1169.
the product alpha-amino acid compound isAt 96% yield, characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.95(s，1H)，7.89-7.79(m，2H)，7.53-7.45(m，3H)，7.44-7.37(m，2H)，7.37-7.26(m，5H)，7.19-7.09(m，2H)，3.77(s，3H)，2.33(s，3H).
13 C NMR(100MHz，CDCl 3 )δ173.1，165.4，138.8，137.8，135.9，134.4，131.8，128.8，128.7，128.5，128.1，127.9，127.5，127.2，70.0，53.7，21.2.
ESIHRMS：m/z Calcd.For C 23 H 21 NO 3 ：(M+Na) + 382.1414.Found：382.1415.
the product alpha-amino acid compound isAt 84% yield, the characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.98(dt，J＝6.8，3.6Hz，1H)，7.87(m，2H)，7.58-7.29(m，9H)，7.26-7.08(m，3H)，3.81(dt，J＝6.8，3.6Hz，3H)，2.25(dq，J＝6.8，3.6Hz，3H).
13 C NMR(100MHz，CDCl 3 )δ173.6，165.4，137.8，137.1，136.2，134.3，131.9，131.8，131.4，128.8，128.5，128.4，128.2(4)，128.2(0)，127.3，125.1，70.3，53.9，20.6.
ESIHRMS：m/z Calcd.For C 23 H 21 NO 3 ：(M+Na) + 382.1414.Found：382.1419.
the product alpha-amino acid compound isAt 30% yield, the characterization results were as follows:
1 H NMR(400MHz，CDCl 3 )δ7.56(d，J＝10.8Hz，4H)，7.34-7.25(m，6H)，7.00(d，J＝2.4Hz，2H)，6.67-6.58(m，1H)，6.44(d，J＝10.4Hz，2H)，5.43(s，1H)，3.69(s，3H).
13 C NMR(100MHz，CDCl 3 )δ173.8，145.3，140.2，128.7，128.5，128.3，127.8，118.1，115.6，71.7，53.3.
ESIHRMS：m/z Calcd.For C 21 H 19 NO 2 ：(M+Na) + 340.1308.Found：340.1301.
example 2
The procedure is as in example 1, except that the reactants and amounts used are as shown in Table 1:
table 1 amounts of reactants, reaction conditions and yields of products
/>
a Yeilds were determined by 1 HNMR using 1，2-dichloroethane as an internal standard.
Furthermore, the present inventors studied the mechanism of synthesizing the α -amino acid compound in the present application, and conducted a radical inhibition test according to the equation in the following formula, when 2 equivalents of a radical scavenger such as 2, 6-tetramethylpiperidine-1-oxyl (TEMPO) was added to the reaction system, no product was detected, and 40% of the starting material was recovered, indicating that the reaction may involve a radical process.
The reactants are added with D in standard condition atmosphere 2 Deuterated products can be obtained after O, which indicates that carbanions can be generated in the synthesis process, and the mechanism diagram for synthesizing the alpha-amino acid compound in the invention is shown in figure 1, and the organic small molecule photocatalyst (such as 3 DPAFIPN) is excited by light to generate 3DPAFIPN * Is then subjected to SET with oxalate to provide a strong reductant 3DPAFIPN ·- Simultaneously obtain carbon dioxide radical anions and CO 2 The carbon dioxide radical anion can reduce the imine substrate to form a carbon radical intermediate which can be further reduced by a strong reducing agent 3DPAFIPN ·- Reduction to give a carbanion intermediate, which can then nucleophilic attack the CO produced by the oxalate itself 2 To obtain the alpha-amino acid compound.
In addition, the inventors have conducted experiments with other materials, process operations, and process conditions as described in this specification with reference to the foregoing examples, and have all obtained desirable results.
It should be understood that the technical solution of the present invention is not limited to the above specific embodiments, and all technical modifications made according to the technical solution of the present invention without departing from the spirit of the present invention and the scope of the claims are within the scope of the present invention.
Claims (10)
1. A method for synthesizing an α -amino acid compound, comprising:
in a protective atmosphere, a mixed reaction system comprising an imine compound, a photocatalyst, an oxalate, an additive and a solvent is subjected to an illumination reaction, and then is subjected to esterification treatment to obtain the alpha-amino acid compound.
2. The synthesis method according to claim 1, wherein: the imine compound comprises an imine containing carbonyl and/or aryl imine;
preferably, the carbonyl-containing imine has a structure as shown in formula (I):
wherein Ar is 1 、Ar 2 、Ar 3 Independently selected from aryl groups containing halogen atoms, ester groups, cyano groups, alkyl groups, or alkoxy groups;
preferably, the aryl imine has a structure as shown in formula (II):
wherein Ar is 4 、Ar 5 、Ar 6 Independently selected from aryl groups.
3. According to claimThe synthesis method of 1, which is characterized in that: the photocatalyst comprises 4DPAIPN and Ir (ppy) 3 、Ir[df(CF 3 )ppy] 2 (dtppy)PF 6 、[Ir(dtbbpy)(ppy) 2 ]PF 6 Any one or a combination of more than two of 3DPAFIPN, eosin Y and Eosin B, preferably 3DPAFIPN.
4. The synthesis method according to claim 1, wherein: the oxalate comprises Na 2 C 2 O 4 、SrC 2 O 4 、H 2 C 2 O 4 、[N(CH 3 ) 4 ] 2 C 2 O 4 、[N(CH 2 CH 3 ) 4 ] 2 C 2 O 4 、[N(nBu) 4 ] 2 C 2 O 4 Any one or a combination of two or more of these, preferably [ N (nBu) 4 ] 2 C 2 O 4 。
5. The synthesis method according to claim 1, wherein: the additive comprises any one or more than two of TMG, 2-tertiary butyl-1, 3-tetramethyl guanidine and moroxydine hydrochloride, and preferably TMG.
6. The synthesis method according to claim 1, wherein: the solvent comprises any one or more than two of DMF, DMA, DMSO, NMP, meCN, 1,4-dioxane and MeOH, and DMF is preferred.
7. The synthesis method according to claim 1, wherein: the molar ratio of the imine compound to the photocatalyst to the oxalate to the additive is 1:0.01-0.02:0.9-2:0.6-2.
8. The synthesis method according to claim 1, characterized in that it comprises in particular: the imine compound, the photocatalyst, the oxalate and the additive are placed in a reaction vessel, then the solvent is added in the protective atmosphere, and the reaction is stirred for 2h to 12h at room temperature under the condition of visible light irradiation.
9. The method of synthesis according to claim 8, wherein: the wavelength of the visible light is 400-550 nm.
10. The synthesis method according to claim 1, characterized in that it comprises in particular: after the light reaction is completed, methyl iodide is added into the obtained reaction system for esterification treatment, and then separation and purification are carried out.
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