CN113943220B - 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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- CN113943220B CN113943220B CN202010689463.9A CN202010689463A CN113943220B CN 113943220 B CN113943220 B CN 113943220B CN 202010689463 A CN202010689463 A CN 202010689463A CN 113943220 B CN113943220 B CN 113943220B
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- 238000001308 synthesis method Methods 0.000 title claims abstract description 7
- 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 17
- -1 acrylic ester compounds Chemical class 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 14
- 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
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical group CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 239000012043 crude product Substances 0.000 claims description 14
- 239000012074 organic phase Substances 0.000 claims description 14
- 239000002904 solvent 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
- 238000004440 column chromatography Methods 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- NJBCRXCAPCODGX-UHFFFAOYSA-N 2-methyl-n-(2-methylpropyl)propan-1-amine Chemical compound CC(C)CNCC(C)C NJBCRXCAPCODGX-UHFFFAOYSA-N 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 2
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 claims description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 239000003208 petroleum Substances 0.000 claims description 2
- 239000000047 product Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims 1
- 229920006391 phthalonitrile polymer Polymers 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 54
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 230000001590 oxidative effect Effects 0.000 abstract description 5
- 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
- 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
- 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
- 239000007788 liquid Substances 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
- 150000002576 ketones Chemical class 0.000 description 6
- 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
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000002194 synthesizing effect Effects 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
- 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 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 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
- 238000005691 oxidative coupling 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
- 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
- 241000233866 Fungi Species 0.000 description 1
- 238000007296 Stetter synthesis reaction Methods 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000036436 anti-hiv Effects 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
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000005283 haloketone group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000000543 intermediate Substances 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
- 238000006053 organic 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
- 238000000746 purification Methods 0.000 description 1
- 239000012048 reactive intermediate Substances 0.000 description 1
- 230000001603 reducing effect Effects 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
- 238000000926 separation method Methods 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000000126 substance Substances 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)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the field of organic synthesis, and discloses a photochemical synthesis method of a1, 4-dicarbonyl compound derivative. The method takes acrylic ester compounds and amine compounds as raw materials, takes 2,4,5, 6-tetra (9-carbazolyl) -isophthalonitrile (4 CzIPN) as a catalyst, reacts at 80 ℃ under blue light irradiation, and takes air as an oxidant to synthesize the 1, 4-dicarbonyl compound derivatives. The invention uses cheap and easily available acrylic ester and amine compounds as raw materials, uses air as an oxidant, reacts under the photocatalysis condition, has mild reaction condition and high product selectivity and yield, and has wide development prospect.
Description
Technical Field
The invention relates to a photochemical synthesis method of a1, 4-dicarbonyl compound derivative, belonging to the technical field of organic synthetic chemistry.
Background
1, 4-Dicarbonyl compounds are common intermediates in organic synthesis and are commonly used for preparing five-membered heterocyclic furan, thiophene, pyrrole and cyclopentenones, and the structural units are widely existing in natural products and drug molecules. For example, herquline A and Amphidinolide F, wherein Herquline A is a metabolite of fungi which inhibits platelet aggregation and has antiviral effects; amphidinolide F is isolated from marine organisms and has cytotoxicity reducing effect. In addition, bevirimat is a kind of anti-HIV drug, and has shown good clinical activity.
The synthesis of 1, 4-dicarbonyl compounds has so far mainly been:
1. The synthesis of aldehydes with α, β -unsaturated ketones by Stetter reaction is the most common method, and Barrett et al in 2004 found that aldehydes with α, β -unsaturated ketones can be synthesized in one step to 1, 4-dicarbonyl compounds (Organic Letters,2004,6 (19): 3377-3380.);
2. The hydroalkylation synthesis of aldehydes and α, β -unsaturated ketones under the action of metal catalysts, osborne and Willis reported in 2008 to use rhodium as a catalyst, and the reaction of aldehydes and α, β -unsaturated ketones can give 1, 4-dicarbonyl compounds (Chemical Communications,2008, 40:5025-5027.);
3. The method utilizes active alpha-H to generate a new C-C bond at alpha position by oxidative coupling, thereby synthesizing a1, 4-dicarbonyl compound, and the object group of Xu Dong in 2010 realizes the oxidative coupling of the 1, 3-dicarbonyl compound by ceric ammonium nitrate, and synthesizes the 1, 4-dicarbonyl compound. (SYNTHETIC COMMUNICATIONS,2010,40 (12): 1847-1855.)
4. And synthesizing the 1, 4-dicarbonyl compound by base catalysis. In 2006, nishiyama et al used α -bromoacetophenone as a raw material and tetra (dimethylamino) ethylene (TDAE) as an alkaline catalyst, and could directly obtain the product 1, 4-dicarbonyl compound through a bimolecular reaction. (Tetrahedron Letters,2006,47 (31): 5565-5567.)
5. And reacting enol silyl ether with halogenated ketone to synthesize the 1, 4-dicarbonyl compound. The Tang dynasty group of topics in 2015 reported the work of synthesizing 1, 4-dicarbonyl compounds by reacting enolic anions with haloketones under alkaline (Na 2CO3) conditions, the reactive intermediates generated under these reaction conditions being alkoxy ions.
These processes generally require an equivalent or excessive amount of alkali, which causes an atom economy problem, while generating a large amount of metal salt waste, severely polluting the environment. Compared with the prior art, the invention has the remarkable advantages that:
Disclosure of Invention
The invention aims to provide a photochemical synthesis method of a1, 4-dicarbonyl compound derivative. The method takes acrylic ester and amine as raw materials, and synthesizes the 1, 4-dicarbonyl compound derivative under the photocatalysis condition.
The technical scheme of the invention is as follows:
the structural formula of the 1, 4-dicarbonyl compound derivative is shown as a formula (III):
Raw materials of acrylic ester (formula I) and amine (formula II) are synthesized under the action of blue light irradiation and 2,4,5, 6-tetra (9-carbazolyl) -isophthalonitrile (4 CzIPN) is taken as a photocatalyst, and the reaction general formula is as follows:
wherein R 1 is selected from alkyl or aryl;
R 2,R3 is selected from the group consisting of hydrogen, alkyl or aryl,
R 4 is a group one carbon less than R 2.
The method comprises the following steps:
The molar ratio of acrylic ester to amine is 4:1,2,4,5, 6-tetra (9-carbazolyl) -isophthalonitrile (4 CzIPN), toluene and water are mixed, and reacted for 12 hours at 80 ℃ under blue light irradiation. Cooling to room temperature, adding ethyl acetate to dilute the reaction liquid, extracting, separating an organic phase, drying, concentrating under reduced pressure to obtain a crude product, and obtaining the 1, 4-dicarbonyl compound derivative through column chromatography.
Preferably, the molar ratio of acrylate to amine is 4:1.
Preferably, the molar amount of 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (4 CzIPN) is 4% of the amine.
Preferably, the visible light is blue light.
Preferably, the volume ratio of toluene to water is 3:1.
Preferably, the volume ratio of the column chromatography solvent is 10: petroleum ether of 1: ethyl acetate.
Compared with the prior art, the invention has the remarkable advantages that:
1. Compared with the traditional thermally promoted organic reaction, the method has the advantages of mild condition, simple operation, high reaction activity, good functional group tolerance and the like;
2. The one-pot method directly oxidizes the olefin into ketone by adding, thereby avoiding the prior stepwise operation of continuing adding and oxidizing;
3. Oxygen is used as an oxidant, so that the use of a strong oxidant is avoided, the environment is protected, and the efficient atomic effect is realized;
4. the invention directly carries out addition reaction on alpha-amino radical generated by unprotected primary amine or secondary amine and olefin, thereby avoiding the tedious process of amino protection in organic synthesis.
Detailed Description
The present invention will be described in detail by way of specific examples, but the use and purpose of these examples are only for illustrating the present invention, and are not intended to limit the scope of the present invention in any way.
Example 1: 4-Oxoheptanoic acid benzyl ester
Benzyl acrylate (64.8 mg,0.4 mmol), di-n-butylamine (12.9 mg,0.1 mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4 CzIPN) (3.2 mg,2 mol%), and toluene: water = 3:1 (4 mL) is added into a 25mL reaction tube in sequence, the reaction tube is sealed, the reaction tube is reacted for 12 hours at 80 ℃ under the irradiation of blue light, the reaction tube is cooled to room temperature, 20mL of ethyl acetate is added for dilution, extraction is carried out, and the obtained organic phase is dried by anhydrous magnesium sulfate, and a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound was isolated and purified by silica gel column chromatography to give 17.8mg of a yellow liquid in 76% yield.
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-oxoheptanoic acid ester
Benzyl p-methacrylate (70.5 mg,0.4 mmol), di-n-butylamine (12.9 mg,0.1 mmol), 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (4 CzIPN) (3.2 mg,2 mol%), and toluene: water = 3:1 (4 mL) is added into a 25mL reaction tube in sequence, the reaction tube is sealed, the reaction tube is reacted for 12 hours at 80 ℃ under the irradiation of blue light, the reaction tube is cooled to room temperature, 20mL of ethyl acetate is added for dilution, extraction is carried out, and the obtained organic phase is dried by anhydrous magnesium sulfate, and a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound was isolated and purified by silica gel column chromatography to give 16.6mg of a yellow liquid 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-oxoheptanoic acid ester
Benzyl p-methoxypcrylate (64.8 mg,0.4 mmol), di-n-butylamine (12.9 mg,0.1 mmol), 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (4 CzIPN) (3.2 mg,2 mol%), and toluene: water = 3:1 (4 mL) is added into a 25mL reaction tube in sequence, the reaction tube is sealed, the reaction tube is reacted for 12 hours at 80 ℃ under the irradiation of blue light, the reaction tube is cooled to room temperature, 20mL of ethyl acetate is added for dilution, extraction is carried out, and the obtained organic phase is dried by anhydrous magnesium sulfate, and a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound was isolated and purified by silica gel column chromatography to give 18.4mg of a yellow liquid in 68% 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 4: 4-chlorobenzyl 4-oxoheptanoate
Benzyl p-chloroacrylate (78.4 mg,0.4 mmol), di-n-butylamine (12.9 mg,0.1 mmol), 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (4 CzIPN) (3.2 mg,2 mol%), and toluene: water = 3:1 (4 mL) is added into a 25mL reaction tube in sequence, the reaction tube is sealed, the reaction tube is reacted for 12 hours at 80 ℃ under the irradiation of blue light, the reaction tube is cooled to room temperature, 20mL of ethyl acetate is added for dilution, extraction is carried out, and the obtained organic phase is dried by anhydrous magnesium sulfate, and a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound was isolated and purified by silica gel column chromatography to give 16.1mg of a yellow liquid in 60% yield.
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 (84.8 mg,0.4 mmol), di-n-butylamine (12.9 mg,0.1 mmol), 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (4 CzIPN) (3.2 mg,2 mol%), and toluene: water = 3:1 (4 mL) is added into a 25mL reaction tube in sequence, the reaction tube is sealed, the reaction tube is reacted for 12 hours at 80 ℃ under the irradiation of blue light, the reaction tube is cooled to room temperature, 20mL of ethyl acetate is added for dilution, extraction is carried out, and the obtained organic phase is dried by anhydrous magnesium sulfate, and a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound was isolated and purified by silica gel column chromatography to give 16.8mg of a yellow liquid with a yield of 59%.
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 (51.3 mg,0.4 mmol), di-n-butylamine (12.9 mg,0.1 mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4 CzIPN) (3.2 mg,2 mol%), and toluene: water = 3:1 (4 mL) is added into a 25mL reaction tube in sequence, the reaction tube is sealed, the reaction tube is reacted for 12 hours at 80 ℃ under the irradiation of blue light, the reaction tube is cooled to room temperature, 20mL of ethyl acetate is added for dilution, extraction is carried out, and the obtained organic phase is dried by anhydrous magnesium sulfate, and a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound was isolated and purified by silica gel column chromatography to give 13.6mg of a yellow liquid 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 (51.3 mg,0.4 mmol), di-n-butylamine (12.9 mg,0.1 mmol), 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (4 CzIPN) (3.2 mg,2 mol%), and toluene: water = 3:1 (4 mL) is added into a 25mL reaction tube in sequence, the reaction tube is sealed, the reaction tube is reacted for 12 hours at 80 ℃ under the irradiation of blue light, the reaction tube is cooled to room temperature, 20mL of ethyl acetate is added for dilution, extraction is carried out, and the obtained organic phase is dried by anhydrous magnesium sulfate, and a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound was isolated and purified by silica gel column chromatography, 12.6mg of a yellow liquid was obtained in 63% yield.
Example 8: n, N-dimethyl-4-oxoheptanamide
N, N-dimethylacrylamide (39.7 mg,0.4 mmol), di-N-butylamine (12.9 mg,0.1 mmol), 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (4 CzIPN) (3.2 mg,2 mol%), and toluene: water = 3:1 (4 mL) is added into a 25mL reaction tube in sequence, the reaction tube is sealed, the reaction tube is reacted for 12 hours at 80 ℃ under the irradiation of blue light, the reaction tube is cooled to room temperature, 20mL of ethyl acetate is added for dilution, extraction is carried out, and the obtained organic phase is dried by anhydrous magnesium sulfate, and a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound was isolated and purified by silica gel column chromatography to give 9.8mg of a yellow liquid in 57% yield.
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 (64.8 mg,0.4 mmol), diethylamine (7.3 mg,0.1 mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4 CzIPN) (3.2 mg,2 mol%), and toluene: water = 3:1 (4 mL) is added into a 25mL reaction tube in sequence, the reaction tube is sealed, the reaction tube is reacted for 12 hours at 80 ℃ under the irradiation of blue light, the reaction tube is cooled to room temperature, 20mL of ethyl acetate is added for dilution, extraction is carried out, and the obtained organic phase is dried by anhydrous magnesium sulfate, and a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound was isolated and purified by silica gel column chromatography to give 11.3mg of 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 (64.8 mg,0.4 mmol), diisobutylamine (12.9 mg,0.1 mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4 CzIPN) (3.2 mg,2 mol%), and toluene: water = 3:1 (4 mL) is added into a 25mL reaction tube in sequence, the reaction tube is sealed, the reaction tube is reacted for 12 hours at 80 ℃ under the irradiation of blue light, the reaction tube is cooled to room temperature, 20mL of ethyl acetate is added for dilution, extraction is carried out, and the obtained organic phase is dried by anhydrous magnesium sulfate, and a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound was isolated and purified by silica gel column chromatography to give 12.6mg of 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 (64.8 mg,0.4 mmol), dibenzylamine (19.7 mg,0.1 mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4 CzIPN) (3.2 mg,2 mol%), and toluene: water = 3:1 (4 mL) is added into a 25mL reaction tube in sequence, the reaction tube is sealed, the reaction tube is reacted for 12 hours at 80 ℃ under the irradiation of blue light, the reaction tube is cooled to room temperature, 20mL of ethyl acetate is added for dilution, extraction is carried out, and the obtained organic phase is dried by anhydrous magnesium sulfate, and a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound was obtained by separation and purification by silica gel column chromatography as a yellow liquid (6.7 mg, 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 (64.8 mg,0.4 mmol), n-butylamine (7.3 mg,0.1 mmol), 2,4,5,6 tetrakis (9-carbazolyl) -isophthalonitrile (4 CzIPN) (3.2 mg,2 mol%), and toluene: water = 3:1 (4 mL) is added into a 25mL reaction tube in sequence, the reaction tube is sealed, the reaction tube is reacted for 12 hours at 80 ℃ under the irradiation of blue light, the reaction tube is cooled to room temperature, 20mL of ethyl acetate is added for dilution, extraction is carried out, and the obtained organic phase is dried by anhydrous magnesium sulfate, and a rotary evaporator is used for removing the solvent to obtain a crude product; the target compound was isolated and purified by silica gel column chromatography to give 7.0mg of a yellow liquid in 76% yield.
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 specific steps:Mixing acrylic ester, amine, 2,4,5, 6-tetra (9-carbazolyl) -m-phthalonitrile, toluene and water in air, reacting for 12 hours at 80 ℃ under the irradiation of visible light, cooling to room temperature, adding ethyl acetate to dilute reaction liquid, extracting, separating organic phase, drying, concentrating to obtain crude product, and obtaining pure product of 1, 4-dicarbonyl compound derivative through column chromatography, wherein the amine is di-n-butylamine, diethylamine, diisobutylamine, dibenzylamine or n-butylamine.
- 2. The synthesis method according to claim 1, wherein the structural formula of the acrylic ester is shown as formula IWherein R 1 is selected from aryl or alkyl.
- 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 is 4% of the amine.
- 5. The method of claim 1, wherein the visible light is blue light.
- 6. The method according to claim 1, wherein the volume ratio of toluene to water is 3:1.
- 7. The method according to claim 1, wherein the column chromatography solvent is in a volume ratio of 10: petroleum ether of 1: ethyl acetate.
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