CN113943220A - Photochemical synthesis method of 1, 4-dicarbonyl compound derivative - Google Patents
Photochemical synthesis method of 1, 4-dicarbonyl compound derivative Download PDFInfo
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- CN113943220A CN113943220A CN202010689463.9A CN202010689463A CN113943220A CN 113943220 A CN113943220 A CN 113943220A CN 202010689463 A CN202010689463 A CN 202010689463A CN 113943220 A CN113943220 A CN 113943220A
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- dicarbonyl compound
- amine
- isophthalonitrile
- carbazolyl
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- 238000001308 synthesis method Methods 0.000 title claims abstract description 8
- PRWATGACIORDEL-UHFFFAOYSA-N 2,4,5,6-tetra(carbazol-9-yl)benzene-1,3-dicarbonitrile Chemical compound C12=CC=CC=C2C2=CC=CC=C2N1C1=C(C#N)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C(N2C3=CC=CC=C3C3=CC=CC=C32)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C1C#N PRWATGACIORDEL-UHFFFAOYSA-N 0.000 claims abstract description 35
- 238000000034 method Methods 0.000 claims abstract description 13
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 48
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 15
- 239000012043 crude product Substances 0.000 claims description 14
- 239000012074 organic phase Substances 0.000 claims description 14
- 150000001412 amines Chemical class 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 239000003208 petroleum Substances 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims 1
- 238000002156 mixing Methods 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 54
- -1 acrylate compound Chemical class 0.000 abstract description 12
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 5
- 239000003054 catalyst Substances 0.000 abstract description 4
- 239000007800 oxidant agent Substances 0.000 abstract description 4
- 230000001590 oxidative effect Effects 0.000 abstract description 4
- 238000007146 photocatalysis Methods 0.000 abstract description 2
- 230000001699 photocatalysis 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 44
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 description 16
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- 238000010790 dilution Methods 0.000 description 12
- 239000012895 dilution Substances 0.000 description 12
- 238000000605 extraction Methods 0.000 description 12
- 238000010898 silica gel chromatography Methods 0.000 description 12
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 239000007788 liquid Substances 0.000 description 10
- 150000002576 ketones Chemical class 0.000 description 8
- GCTPMLUUWLLESL-UHFFFAOYSA-N benzyl prop-2-enoate Chemical compound C=CC(=O)OCC1=CC=CC=C1 GCTPMLUUWLLESL-UHFFFAOYSA-N 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 150000002085 enols Chemical class 0.000 description 3
- CBXRMKZFYQISIV-UHFFFAOYSA-N 1-n,1-n,1-n',1-n',2-n,2-n,2-n',2-n'-octamethylethene-1,1,2,2-tetramine Chemical group CN(C)C(N(C)C)=C(N(C)C)N(C)C CBXRMKZFYQISIV-UHFFFAOYSA-N 0.000 description 2
- VLOUARUYJFXXNO-UHFFFAOYSA-N Amphidinolide F Natural products C1C(=O)OC(C=CC=C(C)C)C(O2)CCC2CC(=O)CC(C)C(=O)CC(O)C(C)C(C)=CC(=C)C(O)C(O)C2CC(C)C1O2 VLOUARUYJFXXNO-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- UFKNDVKQCSBIQE-UHFFFAOYSA-N Herquline A Natural products N12CC(CC=3CCC(=O)C4C=3)N(C)CC2CC2C1C4C(=O)CC2 UFKNDVKQCSBIQE-UHFFFAOYSA-N 0.000 description 2
- SSRSWQDVPRFLOC-UHFFFAOYSA-N O=C(CCC(=O)OCC1=CC=CC=C1)CCC Chemical compound O=C(CCC(=O)OCC1=CC=CC=C1)CCC SSRSWQDVPRFLOC-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- VLOUARUYJFXXNO-VMHIOKEMSA-N amphidinolide f Chemical compound C1C(=O)OC(\C=C\C=C(C)C)C(O2)CCC2CC(=O)CC(C)C(=O)CC(O)C(C)\C(C)=C\C(=C)C(O)C(O)C2CC(C)C1O2 VLOUARUYJFXXNO-VMHIOKEMSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- UFKNDVKQCSBIQE-OCANJJRCSA-N herquline Chemical compound N12C[C@H](CC=3CCC(=O)[C@@H]4C=3)N(C)C[C@@H]2C[C@@H]2[C@H]1[C@@H]4C(=O)CC2 UFKNDVKQCSBIQE-OCANJJRCSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 238000006053 organic reaction Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- RNAMYOYQYRYFQY-UHFFFAOYSA-N 2-(4,4-difluoropiperidin-1-yl)-6-methoxy-n-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine Chemical compound N1=C(N2CCC(F)(F)CC2)N=C2C=C(OCCCN3CCCC3)C(OC)=CC2=C1NC1CCN(C(C)C)CC1 RNAMYOYQYRYFQY-UHFFFAOYSA-N 0.000 description 1
- NJBCRXCAPCODGX-UHFFFAOYSA-N 2-methyl-n-(2-methylpropyl)propan-1-amine Chemical compound CC(C)CNCC(C)C NJBCRXCAPCODGX-UHFFFAOYSA-N 0.000 description 1
- CFVWNXQPGQOHRJ-UHFFFAOYSA-N 2-methylpropyl prop-2-enoate Chemical compound CC(C)COC(=O)C=C CFVWNXQPGQOHRJ-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical class O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 238000007296 Stetter synthesis reaction Methods 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 230000000840 anti-viral effect Effects 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
- 238000005815 base catalysis Methods 0.000 description 1
- ROBFNYBWJKITEN-UHFFFAOYSA-N benzyl 4-oxo-4-phenylbutanoate Chemical compound C=1C=CC=CC=1COC(=O)CCC(=O)C1=CC=CC=C1 ROBFNYBWJKITEN-UHFFFAOYSA-N 0.000 description 1
- RHRNPNZEIHOTSO-UHFFFAOYSA-N benzyl 5-methyl-4-oxohexanoate Chemical compound CC(C)C(=O)CCC(=O)OCC1=CC=CC=C1 RHRNPNZEIHOTSO-UHFFFAOYSA-N 0.000 description 1
- QNRYOQRUGRVBRL-UHFFFAOYSA-N benzyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCC1=CC=CC=C1 QNRYOQRUGRVBRL-UHFFFAOYSA-N 0.000 description 1
- YJEJKUQEXFSVCJ-WRFMNRASSA-N bevirimat Chemical compound C1C[C@H](OC(=O)CC(C)(C)C(O)=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C(=C)C)[C@@H]5[C@H]4CC[C@@H]3[C@]21C YJEJKUQEXFSVCJ-WRFMNRASSA-N 0.000 description 1
- 229950002892 bevirimat Drugs 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- CVYRZWSWSAKZBT-UHFFFAOYSA-N methyl 2-naphthalen-1-ylprop-2-enoate Chemical compound C1=CC=C2C(C(=C)C(=O)OC)=CC=CC2=C1 CVYRZWSWSAKZBT-UHFFFAOYSA-N 0.000 description 1
- 229940088644 n,n-dimethylacrylamide Drugs 0.000 description 1
- YLGYACDQVQQZSW-UHFFFAOYSA-N n,n-dimethylprop-2-enamide Chemical compound CN(C)C(=O)C=C YLGYACDQVQQZSW-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- 239000011941 photocatalyst Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000010405 reoxidation reaction Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C67/347—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to unsaturated carbon-to-carbon bonds
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
Abstract
The invention belongs to the field of organic synthesis, and discloses a photochemical synthesis method of 1, 4-dicarbonyl compound derivatives. The method takes an acrylate compound and an amine compound as raw materials, takes 2,4,5, 6-tetra (9-carbazolyl) -isophthalonitrile (4CzIPN) as a catalyst, reacts at 80 ℃ under the irradiation of blue light, and takes air as an oxidant to synthesize the 1, 4-dicarbonyl compound derivative. The invention uses cheap and easily obtained acrylate and amine compounds as raw materials, uses air as an oxidant, and reacts under the photocatalysis condition, and has mild reaction condition, high product selectivity and yield and wide development prospect.
Description
Technical Field
The invention relates to a photochemical synthesis method of 1, 4-dicarbonyl compound derivatives, belonging to the technical field of organic synthesis chemistry.
Background
The 1, 4-dicarbonyl compound is a common intermediate in organic synthesis and is commonly used for preparing five-membered heterocyclic furan, thiophene, pyrrole and cyclopentenone compounds, and the structural units are widely present in natural products and drug molecules. For example, Herquline A and Amphidinolide F, wherein Herquline A is a fungal metabolite which inhibits platelet aggregation and has antiviral effects; the Amphidinolide F is separated from marine organisms and has the effect of reducing cytotoxicity. In addition, Bevirimat is a medicine for resisting HIV virus, and has shown good activity in clinic.
The synthesis of 1, 4-dicarbonyl compounds so far has mainly been:
1. the synthesis of aldehydes and α, β -unsaturated ketones by the Stetter reaction is the most common method, Barrett et al, 2004 found that aldehydes and α, β -unsaturated ketones can be synthesized into 1, 4-dicarbonyl compounds in one step (Organic Letters,2004,6(19): 3377-3380.);
2. aldehyde and alpha, beta-unsaturated ketone are synthesized by hydrogen alkyl acylation under the action of a metal catalyst, and Osborne and Willis report that rhodium is used as a catalyst in 2008, and the aldehyde and the alpha, beta-unsaturated ketone react to obtain a 1, 4-dicarbonyl compound (Chemical Communications,2008,40: 5025-5027.);
3. ketone or enol oxidation coupling, which utilizes active alpha-H to generate a new C-C bond at the alpha position through oxidation coupling so as to synthesize a 1, 4-dicarbonyl compound, wherein in 2010, the oxidation coupling of the 1, 3-dicarbonyl compound is realized through cerium ammonium nitrate to synthesize the 1, 4-dicarbonyl compound. (Synthetic Communications,2010,40(12): 1847-
4. Synthesizing 1, 4-dicarbonyl compound by base catalysis. In 2006, Nishiyama and the like can directly obtain a product 1, 4-dicarbonyl compound by bimolecular reaction with alpha-bromoacetophenone as a raw material and tetra (dimethylamino) ethylene (TDAE) as an alkaline catalyst. (Tetrahedron Letters,2006,47(31): 5565-
5. The enol silyl ether reacts with halogenated ketone to synthesize the 1, 4-dicarbonyl compound. In 2015, Tangqiang subjects reported to be alkaline (Na)2CO3) Under the condition, enol negative ions and halogenated ketone react to synthesize the 1, 4-dicarbonyl compound, and an active intermediate generated under the reaction condition is alkoxy ions.
These processes usually require an equivalent or excess amount of base, which causes problems in atom economy, and also generate a large amount of metal salt waste, which seriously pollutes the environment. Compared with the prior art, the invention has the following remarkable advantages:
disclosure of Invention
The invention aims to provide a photochemical synthesis method of a 1, 4-dicarbonyl compound derivative. The method takes acrylic ester and amine as raw materials to synthesize the 1, 4-dicarbonyl compound derivative under the photocatalysis condition.
The technical scheme of the invention comprises the following steps:
the structural formula of the 1, 4-dicarbonyl compound derivative is shown as the formula (III):
raw materials of acrylic ester (formula I) and amine (formula II) are synthesized under the irradiation of blue light and the action of 2,4,5, 6-tetra (9-carbazolyl) -isophthalonitrile (4CzIPN) as a photocatalyst, and the reaction general formula is as follows:
wherein R is1Selected from alkyl or aryl;
R2，R3selected from the group consisting of hydrogen, alkyl or aryl,
R4is a ratio R2A group having one less carbon.
The method comprises the following steps:
according to the molar ratio of the acrylate to the amine of 4: 1, 2,4,5, 6-tetra (9-carbazolyl) -isophthalonitrile (4CzIPN), a solvent of toluene and water are mixed and reacted for 12 hours at 80 ℃ under the irradiation of blue light. Cooling to room temperature, adding ethyl acetate to dilute the reaction solution, extracting, separating an organic phase, drying, concentrating under reduced pressure to obtain a crude product, and performing column chromatography to obtain the 1, 4-dicarbonyl compound derivative.
Preferably, the molar ratio of acrylate to amine is 4: 1.
preferably, the molar amount of 2,4,5,6 tetra (9-carbazolyl) -isophthalonitrile (4CzIPN) is 4% of the amine.
Preferably, the visible light is blue light.
Preferably, the volume ratio of the toluene to the water is 3: 1.
preferably, the column chromatography solvent is a mixture of 10: 1 petroleum ether: and (3) ethyl acetate.
Compared with the prior art, the invention has the following remarkable advantages:
1. the method utilizes visible light induced organic reaction, and has the advantages of mild condition, simple and convenient operation, high reaction activity, good functional group tolerance and the like compared with the traditional thermal organic reaction;
2. the one-pot method of the invention directly carries out addition and reoxidation of the olefin to ketone, thus avoiding the prior step-by-step operation of first addition and then oxidation;
3. oxygen is used as an oxidant, so that the use of a strong oxidant is avoided, and the method is green and environment-friendly and has a high-efficiency atomic effect;
4. the invention directly carries out addition reaction on alpha-amino free radicals generated by unprotected primary amine or secondary amine and olefin, thereby avoiding the complex process of amino protection in organic synthesis.
Detailed Description
The present invention is described in detail by the following specific examples, but the use and purpose of these examples are only to illustrate the present invention, and not to constitute any limitation to the scope of the present invention in any form, and the scope of the present invention is not limited thereto.
Example 1: 4-Oxoheptanoic acid benzyl ester
Benzyl acrylate (64.8mg, 0.4mmol), di-n-butylamine (12.9mg, 0.1mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4CzIPN) (3.2mg, 2 mol%), and toluene: water 3: 1(4mL) is sequentially added into a 25mL reaction tube, the reaction tube is sealed, the reaction is carried out for 12h at 80 ℃ under the irradiation of blue light, the reaction is cooled to room temperature, 20mL ethyl acetate is added for dilution and extraction, the obtained organic phase is dried by anhydrous magnesium sulfate, and then a rotary evaporator is used for removing the solvent to obtain a crude product; separation and purification by silica gel column chromatography gave 17.8mg of the objective compound as a yellow liquid in a yield of 76%.
1H NMR(500MHz,CDCl3)δ7.35(qd,J＝7.0,2.4Hz,5H),5.12(s,2H),2.73(t,J＝6.2Hz,2H),2.65(t,J＝6.2Hz,2H),2.42(t,J＝7.4Hz,2H),1.62(h,J＝7.4Hz,2H),0.91(t,J＝7.4Hz,3H).
13C NMR(126MHz,CDCl3)δ209.0,172.7,135.9,128.6,128.3,128.2,66.5,44.7,37.0,28.0,17.3,13.7.
Example 2: 4-methylbenzyl 4-oxoheptanoate
Benzyl p-methacrylate (70.5mg, 0.4mmol), di-n-butylamine (12.9mg, 0.1mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4CzIPN) (3.2mg, 2 mol%), and toluene: water 3: 1(4mL) is sequentially added into a 25mL reaction tube, the reaction tube is sealed, the reaction is carried out for 12h at 80 ℃ under the irradiation of blue light, the reaction is cooled to room temperature, 20mL ethyl acetate is added for dilution and extraction, the obtained organic phase is dried by anhydrous magnesium sulfate, and then a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound (16.6 mg) was isolated and purified by silica gel column chromatography in 67% yield.
1H NMR(500MHz,CDCl3)δ7.33–7.27(m,2H),7.22(d,J＝7.8Hz,2H),5.12(s,2H),2.77(t,J＝6.5Hz,2H),2.68(t,J＝6.4Hz,2H),2.47(t,J＝7.4Hz,2H),2.40(s,3H),1.66(dt,J＝14.7,7.4Hz,2H),0.96(t,J＝7.4Hz,3H).
13C NMR(126MHz,CDCl3)δ209.0,172.8,138.1,132.9,129.3,128.4,66.5,44.7,37.0,28.0,21.2,17.3,13.7.
Example 3: 4-methoxybenzyl 4-oxoheptanoate
Benzyl p-methoxyacrylate (64.8mg, 0.4mmol), di-n-butylamine (12.9mg, 0.1mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4CzIPN) (3.2mg, 2 mol%), and toluene: water 3: 1(4mL) is sequentially added into a 25mL reaction tube, the reaction tube is sealed, the reaction is carried out for 12h at 80 ℃ under the irradiation of blue light, the reaction is cooled to room temperature, 20mL ethyl acetate is added for dilution and extraction, the obtained organic phase is dried by anhydrous magnesium sulfate, and then a rotary evaporator is used for removing the solvent to obtain a crude product; separation and purification by silica gel column chromatography gave 18.4mg of the objective compound as a yellow liquid in a yield of 68%.
1H NMR(500MHz,CDCl3)δ7.33–7.27(m,2H),7.22(d,J＝7.8Hz,2H),5.12(s,2H),2.77(t,J＝6.5Hz,2H),2.68(t,J＝6.4Hz,2H),2.47(t,J＝7.4Hz,2H),2.40(s,3H),1.66(dt,J＝14.7,7.4Hz,2H),0.96(t,J＝7.4Hz,3H).
13C NMR(126MHz,CDCl3)δ209.0,172.8,138.1,132.9,129.3,128.4,66.5,44.7,37.0,28.0,21.2,17.3,13.7.
Example 4: 4-chlorobenzyl 4-oxoheptanoate
Benzyl p-chloroacrylate (78.4mg, 0.4mmol), di-n-butylamine (12.9mg, 0.1mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4CzIPN) (3.2mg, 2 mol%), and toluene: water 3: 1(4mL) is sequentially added into a 25mL reaction tube, the reaction tube is sealed, the reaction is carried out for 12h at 80 ℃ under the irradiation of blue light, the reaction is cooled to room temperature, 20mL ethyl acetate is added for dilution and extraction, the obtained organic phase is dried by anhydrous magnesium sulfate, and then a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound (16.1 mg) was isolated and purified by silica gel column chromatography to give a yellow liquid with a yield of 60%.
1H NMR(500MHz,CDCl3)δ7.42–7.27(m,5H),5.12(s,2H),2.78(t,J＝6.5Hz,2H),2.68(t,J＝6.4Hz,2H),2.47(t,J＝7.4Hz,2H),1.66(h,J＝7.4Hz,2H),0.96(t,J＝7.4Hz,3H).
13C NMR(126MHz,CDCl3)δ208.9,172.6,134.4,134.1,129.6,128.8,65.6,44.7,37.0,27.9,17.3,13.7.
Example 5: naphthalen-1-ylmethyl 4-oxoheptanoic acid methyl ester
Methyl naphthalen-1-ylacrylate (84.8mg, 0.4mmol), di-n-butylamine (12.9mg, 0.1mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4CzIPN) (3.2mg, 2 mol%), and toluene: water 3: 1(4mL) is sequentially added into a 25mL reaction tube, the reaction tube is sealed, the reaction is carried out for 12h at 80 ℃ under the irradiation of blue light, the reaction is cooled to room temperature, 20mL ethyl acetate is added for dilution and extraction, the obtained organic phase is dried by anhydrous magnesium sulfate, and then a rotary evaporator is used for removing the solvent to obtain a crude product; separation and purification by silica gel column chromatography gave 16.8mg of the title compound as a yellow liquid in 59% yield.
1H NMR(500MHz,CDCl3)δ8.11–7.84(m,3H),7.76–7.44(m,4H),5.63(s,2H),2.74(dt,J＝37.6,6.5Hz,2H),2.44(t,J＝7.3Hz,2H),1.64(h,J＝7.1Hz,2H),0.95(t,J＝7.4Hz,3H).
13C NMR(126MHz,CDCl3)δ208.9,172.8,133.8,131.7,131.4,129.4,128.7,127.5,126.6,126.0,125.3,123.6,64.9,44.7,37.1,28.1,17.3,13.7.
Example 6: 4-Oxoheptanoic acid tert-butyl ester
Tert-butyl acrylate (51.3mg, 0.4mmol), di-n-butylamine (12.9mg, 0.1mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4CzIPN) (3.2mg, 2 mol%), and toluene: water 3: 1(4mL) is sequentially added into a 25mL reaction tube, the reaction tube is sealed, the reaction is carried out for 12h at 80 ℃ under the irradiation of blue light, the reaction is cooled to room temperature, 20mL ethyl acetate is added for dilution and extraction, the obtained organic phase is dried by anhydrous magnesium sulfate, and then a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound (13.6 mg) was isolated and purified by silica gel column chromatography in 68% yield.
1H NMR(500MHz,CDCl3)δ2.71(t,J＝6.6Hz,2H),2.55(t,J＝6.6Hz,2H),2.47(t,J＝7.4Hz,2H),1.70–1.63(m,2H),1.49(s,9H),0.97(t,J＝7.4Hz,3H).
13C NMR(126MHz,CDCl3)δ209.3,172.2,80.6,44.8,37.2,29.2,28.1,17.3,13.8.
Example 7: 4-Oxoheptanoic acid isobutyl ester
Isobutyl acrylate (51.3mg, 0.4mmol), di-n-butylamine (12.9mg, 0.1mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4CzIPN) (3.2mg, 2 mol%), and toluene: water 3: 1(4mL) is sequentially added into a 25mL reaction tube, the reaction tube is sealed, the reaction is carried out for 12h at 80 ℃ under the irradiation of blue light, the reaction is cooled to room temperature, 20mL ethyl acetate is added for dilution and extraction, the obtained organic phase is dried by anhydrous magnesium sulfate, and then a rotary evaporator is used for removing the solvent to obtain a crude product; the objective compound was isolated and purified by silica gel column chromatography to give 12.6mg of a yellow liquid in a yield of 63%.
Example 8: n, N-dimethyl-4-oxyheptanoamide
N, N-dimethylacrylamide (39.7mg, 0.4mmol), di-N-butylamine (12.9mg, 0.1mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4CzIPN) (3.2mg, 2 mol%), and toluene: water 3: 1(4mL) is sequentially added into a 25mL reaction tube, the reaction tube is sealed, the reaction is carried out for 12h at 80 ℃ under the irradiation of blue light, the reaction is cooled to room temperature, 20mL ethyl acetate is added for dilution and extraction, the obtained organic phase is dried by anhydrous magnesium sulfate, and then a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound was separated and purified by silica gel column chromatography to obtain 9.8mg of a yellow liquid in a yield of 57%.
1H NMR(500MHz,CDCl3)δ3.03(s,3H),2.92(s,3H),2.73(t,J＝6.4Hz,2H),2.59(t,J＝6.4Hz,2H),2.47(t,J＝7.4Hz,2H),1.62(h,J＝7.4Hz,2H),0.91(t,J＝7.4Hz,3H).
13C NMR(126MHz,CDCl3)δ210.5,171.7,45.0,37.3,37.1,35.5,27.1,17.3,13.8.
Example 9: benzyl laurate
Benzyl acrylate (64.8mg, 0.4mmol), diethylamine (7.3mg, 0.1mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4CzIPN) (3.2mg, 2 mol%), and toluene: water 3: 1(4mL) is sequentially added into a 25mL reaction tube, the reaction tube is sealed, the reaction is carried out for 12h at 80 ℃ under the irradiation of blue light, the reaction is cooled to room temperature, 20mL ethyl acetate is added for dilution and extraction, the obtained organic phase is dried by anhydrous magnesium sulfate, and then a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound (11.3 mg) was isolated and purified by silica gel column chromatography to give a yellow liquid in 55% yield.
1H NMR(500MHz,CDCl3)δ7.43–7.30(m,5H),5.12(s,2H),2.77(t,J＝6.5Hz,2H),2.64(t,J＝6.5Hz,2H),2.19(s,3H).
13C NMR(126MHz,CDCl3)δ206.6,172.6,135.9,128.6,128.3,128.2,66.5,38.0,29.9,28.0.
Example 10: 5-methyl-4-oxohexanoic acid benzyl ester
Benzyl acrylate (64.8mg, 0.4mmol), diisobutylamine (12.9mg, 0.1mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4CzIPN) (3.2mg, 2 mol%), and toluene: water 3: 1(4mL) is sequentially added into a 25mL reaction tube, the reaction tube is sealed, the reaction is carried out for 12h at 80 ℃ under the irradiation of blue light, the reaction is cooled to room temperature, 20mL ethyl acetate is added for dilution and extraction, the obtained organic phase is dried by anhydrous magnesium sulfate, and then a rotary evaporator is used for removing the solvent to obtain a crude product; separation and purification by silica gel column chromatography gave 12.6mg of the objective compound as a yellow liquid in 54% yield.
1H NMR(500MHz,CDCl3)δ7.44–7.28(m,5H),5.17(s,2H),2.84(t,J＝6.6Hz,2H),2.70(t,J＝6.5Hz,2H),1.17(d,J＝7.0Hz,6H).
13C NMR(126MHz,CDCl3)δ212.6,172.8,136.0,128.6,128.3,128.2,66.5,40.8,34.8,28.1,18.3,.
Example 11: 4-oxo-4-phenylbutyric acid benzyl ester
Benzyl acrylate (64.8mg, 0.4mmol), dibenzylamine (19.7mg, 0.1mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4CzIPN) (3.2mg, 2 mol%), and toluene: water 3: 1(4mL) is sequentially added into a 25mL reaction tube, the reaction tube is sealed, the reaction is carried out for 12h at 80 ℃ under the irradiation of blue light, the reaction is cooled to room temperature, 20mL ethyl acetate is added for dilution and extraction, the obtained organic phase is dried by anhydrous magnesium sulfate, and then a rotary evaporator is used for removing the solvent to obtain a crude product; separating and purifying with silica gel column chromatography to obtain desired compound 6.7mg yellow liquid with yield 25%
1H NMR(500MHz,CDCl3)δ8.04(d,J＝7.4Hz,2H),7.63(t,J＝7.5Hz,1H),7.52(t,J＝7.6Hz,2H),7.44–7.34(m,5H),5.22(s,2H),3.40(t,J＝6.6Hz,2H),2.89(t,J＝6.6Hz,2H).
13C NMR(126MHz,CDCl3)δ198.1,172.8,136.6,136.0,133.3,128.7,128.6,128.3,128.3,128.1,66.6,33.4,28.3.
Example 12: 4-Oxoheptanoic acid benzyl ester
Benzyl acrylate (64.8mg, 0.4mmol), n-butylamine (7.3mg, 0.1mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4CzIPN) (3.2mg, 2 mol%), and toluene: water 3: 1(4mL) is sequentially added into a 25mL reaction tube, the reaction tube is sealed, the reaction is carried out for 12h at 80 ℃ under the irradiation of blue light, the reaction is cooled to room temperature, 20mL ethyl acetate is added for dilution and extraction, the obtained organic phase is dried by anhydrous magnesium sulfate, and then a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound was separated and purified by silica gel column chromatography to obtain 7.0mg of a yellow liquid in a yield of 76%.
1H NMR(500MHz,CDCl3)δ7.35(qd,J＝7.0,2.4Hz,5H),5.12(s,2H),2.73(t,J＝6.2Hz,2H),2.65(t,J＝6.2Hz,2H),2.42(t,J＝7.4Hz,2H),1.62(h,J＝7.4Hz,2H),0.91(t,J＝7.4 Hz,3H).
13C NMR(126 MHz,CDCl3)δ209.0,172.7,135.9,128.6,128.3,128.2,66.5,44.7,37.0,28.0,17.3,13.7.
Claims (7)
- The synthesis method of the 1, 4-dicarbonyl compound derivative is characterized by comprising the following steps:mixing acrylate, amine, 2,4,5, 6-tetra (9-carbazolyl) -isophthalonitrile, toluene and water in the air atmosphere, reacting for 12h at 80 ℃ under the irradiation of visible light, cooling to room temperature, adding ethyl acetate to dilute reaction liquid, extracting, separating an organic phase, drying, concentrating to obtain a crude product, and performing column chromatography to obtain a pure 1, 4-dicarbonyl compound derivative.
- 2. The method of claim 1, wherein the acrylate has the formula shown in formula IWherein R is1Selected from aryl or alkyl; the structural formula of the amine is shown as a formula II
R2，R3Selected from hydrogen, alkyl or aryl.
- 3. The method of claim 1, wherein the molar ratio of acrylate to amine is 4: 1.
- 4. the method according to claim 1, wherein the molar amount of 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4CzIPN) is 4% of the amine.
- 5. The method of claim 1, wherein the visible light is blue light.
- 6. The synthesis method according to claim 1, wherein the volume ratio of toluene to water is 3: 1.
- 7. the synthesis method of claim 1, wherein the column chromatography solvent is a mixture of 10: 1 petroleum ether: and (3) ethyl acetate.
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| YOSHIHIRO MIYAKE等: "Visible-light-mediated addition of a-aminoalkyl radicals generated from a -silylamines to a , b-unsaturated carbonyl compounds", CHEM. COMMUN., vol. 48, pages 6966 - 6968 * |
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