CN114456112B - Synthesis method of benzanthracene derivative - Google Patents
Synthesis method of benzanthracene derivative Download PDFInfo
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- CN114456112B CN114456112B CN202210250938.3A CN202210250938A CN114456112B CN 114456112 B CN114456112 B CN 114456112B CN 202210250938 A CN202210250938 A CN 202210250938A CN 114456112 B CN114456112 B CN 114456112B
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- disodium salt
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- DXBHBZVCASKNBY-UHFFFAOYSA-N 1,2-Benz(a)anthracene Chemical class C1=CC=C2C3=CC4=CC=CC=C4C=C3C=CC2=C1 DXBHBZVCASKNBY-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 238000001308 synthesis method Methods 0.000 title claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 74
- -1 eosin Y disodium salt Chemical class 0.000 claims abstract description 39
- 239000011941 photocatalyst Substances 0.000 claims abstract description 8
- 229940125782 compound 2 Drugs 0.000 claims abstract description 5
- 229940125904 compound 1 Drugs 0.000 claims abstract description 4
- 150000001989 diazonium salts Chemical class 0.000 claims abstract description 4
- 238000005286 illumination Methods 0.000 claims abstract description 3
- 230000027756 respiratory electron transport chain Effects 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 156
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 104
- 239000003208 petroleum Substances 0.000 claims description 52
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 150000003254 radicals Chemical class 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 230000005595 deprotonation Effects 0.000 claims description 2
- 238000010537 deprotonation reaction Methods 0.000 claims description 2
- 239000003480 eluent Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- 238000010898 silica gel chromatography Methods 0.000 claims description 2
- 230000005281 excited state Effects 0.000 claims 2
- ZNBQMNLJFTYCHC-UHFFFAOYSA-N 1,1'-biphenyl;isocyanic acid Chemical compound N=C=O.C1=CC=CC=C1C1=CC=CC=C1 ZNBQMNLJFTYCHC-UHFFFAOYSA-N 0.000 claims 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 abstract description 30
- 238000000034 method Methods 0.000 abstract description 10
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 abstract description 8
- 235000010290 biphenyl Nutrition 0.000 abstract description 4
- 239000004305 biphenyl Substances 0.000 abstract description 4
- 239000002904 solvent Substances 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
- 150000001875 compounds Chemical class 0.000 description 30
- 239000012299 nitrogen atmosphere Substances 0.000 description 26
- 239000003960 organic solvent Substances 0.000 description 26
- 239000000047 product Substances 0.000 description 26
- 238000004809 thin layer chromatography Methods 0.000 description 25
- YVPJCJLMRRTDMQ-UHFFFAOYSA-N ethyl diazoacetate Chemical compound CCOC(=O)C=[N+]=[N-] YVPJCJLMRRTDMQ-UHFFFAOYSA-N 0.000 description 23
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- 239000007787 solid Substances 0.000 description 10
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- VAVHMEQFYYBAPR-ITWZMISCSA-N (e,3r,5s)-7-[4-(4-fluorophenyl)-1-phenyl-2-propan-2-ylpyrrol-3-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound CC(C)C1=C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=CN1C1=CC=CC=C1 VAVHMEQFYYBAPR-ITWZMISCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
- PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 1
- JNPGUXGVLNJQSQ-BGGMYYEUSA-M (e,3r,5s)-7-[4-(4-fluorophenyl)-1,2-di(propan-2-yl)pyrrol-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)N1C(C(C)C)=C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C1 JNPGUXGVLNJQSQ-BGGMYYEUSA-M 0.000 description 1
- MIVRMHJOEYRXQB-UHFFFAOYSA-N 2-diazonio-1-methoxyethenolate Chemical compound COC(=O)C=[N+]=[N-] MIVRMHJOEYRXQB-UHFFFAOYSA-N 0.000 description 1
- JBBKWIFIXPBQGZ-UHFFFAOYSA-N 2-diazonio-1-phenylmethoxyethenolate Chemical compound [N-]=[N+]=CC(=O)OCC1=CC=CC=C1 JBBKWIFIXPBQGZ-UHFFFAOYSA-N 0.000 description 1
- FNXAUCKBTPCLJL-UHFFFAOYSA-N 2-diazonio-1-propan-2-yloxyethenolate Chemical compound CC(C)OC(=O)C=[N+]=[N-] FNXAUCKBTPCLJL-UHFFFAOYSA-N 0.000 description 1
- KPTZIQYZCKOZFH-UHFFFAOYSA-N 2-diazonio-1-propoxyethenolate Chemical compound CCCOC(=O)C=[N+]=[N-] KPTZIQYZCKOZFH-UHFFFAOYSA-N 0.000 description 1
- MWVKLRSIDOXBSE-UHFFFAOYSA-N 5-(1-piperidin-4-ylpyrazol-4-yl)-3-(6-pyrrolidin-1-yl-1,3-benzoxazol-2-yl)pyridin-2-amine Chemical compound NC1=NC=C(C2=CN(N=C2)C2CCNCC2)C=C1C(OC1=C2)=NC1=CC=C2N1CCCC1 MWVKLRSIDOXBSE-UHFFFAOYSA-N 0.000 description 1
- HIHOEGPXVVKJPP-JTQLQIEISA-N 5-fluoro-2-[[(1s)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyridine-3-carbonitrile Chemical compound N([C@@H](C)C=1N=CC(F)=CC=1)C(C(=CC=1F)C#N)=NC=1NC=1C=C(C)NN=1 HIHOEGPXVVKJPP-JTQLQIEISA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- DGJMHKMYSDYOFP-MRXNPFEDSA-N C=CC(N(CCC1)C[C@@H]1N1N=C(C2=CN(CC(C3=CC=CC=C3)(F)F)N=N2)C2=C(N)N=CN=C12)=O Chemical compound C=CC(N(CCC1)C[C@@H]1N1N=C(C2=CN(CC(C3=CC=CC=C3)(F)F)N=N2)C2=C(N)N=CN=C12)=O DGJMHKMYSDYOFP-MRXNPFEDSA-N 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- HGDWHTASNMRJMP-UHFFFAOYSA-N [1-(hydroxyamino)-1-oxo-5-(3-phenoxyphenyl)pentan-2-yl]phosphonic acid Chemical compound ONC(=O)C(P(O)(O)=O)CCCC1=CC=CC(OC=2C=CC=CC=2)=C1 HGDWHTASNMRJMP-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- YBFBENHWPRGUMU-UHFFFAOYSA-N chembl398496 Chemical compound OC(=O)C1=CC=CC=C1NC(=O)N1CCN(C=2N=C3C=CC(O)=CC3=NC=2)CC1 YBFBENHWPRGUMU-UHFFFAOYSA-N 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- AVAACINZEOAHHE-VFZPANTDSA-N doripenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](CNS(N)(=O)=O)C1 AVAACINZEOAHHE-VFZPANTDSA-N 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
- C07D221/12—Phenanthridines
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Abstract
The invention discloses a synthesis method of a benzanthracene derivative, which comprises the steps of firstly generating an excited photocatalyst eosin Y disodium salt by a photocatalyst eosin Y disodium salt under the illumination condition, then carrying out single electron transfer on a diazonium compound 2 and the excited photocatalyst eosin Y disodium salt, then carrying out reaction with a biphenyl isocyanic compound 1 in a solvent, and finally generating a benzanthracene derivative 3 under the action of N, N-diisopropylethylamine. The method uses visible light as green energy to drive, has mild reaction conditions, is easy to operate, and can be used for mass synthesis by a photochemical method.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of a benzanthracene derivative.
Background
Benzanthracene is widely found in natural products and bioactive molecules and has a wide range of pharmacological properties including anti-tumor, antifungal and antiviral activity. Therefore, there is a great interest in developing efficient and practical methods for constructing benzanthracenes.
Since the use of benzanthracenes is very widespread, organic chemists have also successively developed a number of methods for synthesizing benzanthracenes. In recent studies it was found that the preparation of benzanthracene by ortho-aminobiphenyl and acrylate is one of the effective methods, but these processes often require the use of noble metal catalysis before proceeding (pathA). Another effective method is to build up an isocyanide with 1, 3-dimethyl compound (path B) or benzyl alcohol (path C) by a free radical cascade cyclization, usually under conditions of high temperature. However, relatively few methods have been reported for synthesizing benzanthracene under photocatalytic conditions using commercially available ethyl diazoacetate directly as a starting material.
Disclosure of Invention
The research shows that the photocatalyst eosin Y disodium salt generates excited eosin Y disodium salt under the irradiation of a blue LED lamp, then the diazonium compound 2 and the excited eosin Y disodium salt generate single electron transfer to generate alkyl free radicals, the alkyl free radicals are added with biphenyl isocyanic compound 1 to obtain imine free radicals, and then intramolecular cyclization, oxidation and deprotonation are carried out to obtain the benzanthracene derivative 3.
Based on the research background, the invention provides a synthesis method of a benzanthracene derivative, which uses a diazonium compound and a biphenyl isocyanic compound to simply prepare various benzanthracene derivatives under the action of methanol as a solvent by taking eosin Y disodium salt as a photocatalyst and taking N, N-diisopropylethylamine as a base. The method uses visible light as a green energy source for driving.
According to the synthesis method of the benzanthracene derivative, a biphenyl isocyanic compound 1, eosin Y disodium salt, ethyl diazoacetate 2, N-diisopropylethylamine and methanol are added in a nitrogen atmosphere to react under blue light irradiation, and a target product 3 is obtained after separation and purification.
The synthetic route is as follows:
substituent R in Compound 1 1 Can be methyl, methoxy, cyano, trifluoromethyl, phenyl, methoxycarbonyl or halogen, and the substituent R 2 May be methyl, methoxy, cyano, trifluoromethyl, phenyl, methoxycarbonyl or halogen.
Substituent R in Compound 2 3 Is methyl, ethyl, n-propyl, isopropyl or benzyl.
The separation and purification are carried out by silica gel column chromatography, the eluent is petroleum ether and ethyl acetate, and the volume ratio is 10:1-5:1.
Compared with the prior art, the invention has the beneficial effects that:
1. the starting materials used were readily prepared and ethyl diazoacetate was commercially available.
2. And driving illumination is performed by using visible light as a green energy source.
3. Mild reaction condition, easy operation and capacity of synthesizing great amount by photochemical process.
4. Nitrogen is the only byproduct, conforming to the green chemistry concept.
Detailed Description
The technical scheme of the invention is further described in detail below with reference to specific embodiments.
Example 1:
in a 10mL reaction flask, compound 1a (0.2 mmol,35.8 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to perform a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give the pure product as a yellow oil with 73% yield.
Compound 3aa was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝δ8.64(d,J＝8.3Hz,1H),8.53(d,J＝8.0Hz,1H),8.40–8.30(m,1H),8.11(d,J＝8.0Hz,1H),7.83(t,J＝7.6Hz,1H),7.76–7.67(m,2H),7.63(t,J＝7.0Hz,1H),5.23(dd,J＝7.9,6.4Hz,1H),4.23–4.09(m,4H),3.45(dd,J＝17.0,8.2Hz,1H),3.25(dd,J＝17.0,6.2Hz,1H),1.21(t,J＝7.1Hz,3H),1.14(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝δ172.0,171.7,156.8,143.3,133.2,130.4,130.2,128.5,127.5,127.0,125.7,124.9,123.7,122.5,121.8,77.3,77.0,76.7,61.2,60.6,46.0,35.6,14.1,14.0.
high resolution: calculated values: [ M+H ]] + 352.1549, found: 352.1531.
example 2:
in a 10mL reaction flask, compound 1a (0.2 mmol,35.8 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), base (0.2 mmol), and methanol (1 mL) were added under nitrogen atmosphere to react under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give pure product.
| Alkali | Yield (%) |
| Dipotassium hydrogen phosphate | 13 |
| Sodium carbonate | 22 |
| Triethylene diamine | 54 |
| N, N-diisopropylethylamine | 64 |
| Triethylamine | 58 |
Example 3:
in a 10mL reaction flask, compound 1a (0.2 mmol,35.8 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg) and an organic solvent (1 mL) were added under nitrogen atmosphere to react under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give pure product.
| Solvent(s) | Yield (%) |
| Dichloromethane (dichloromethane) | 10 |
| Acetonitrile | 32 |
| N, N-dimethylformamide | 41 |
| Ethanol | 54 |
Example 4:
in a 10mL reaction flask, compound 1b (0.2 mmol,41.8 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to perform a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give the pure product as a yellow oil with a yield of 78%.
Compound 3ba was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝8.54(d,J＝9.1Hz,1H),8.44(d,J＝8.0Hz,1H),8.12–8.06(m,1H),7.71(d,J＝2.3Hz,1H),7.65–7.57(m,2H),7.46(dd,J＝9.0,2.3Hz,1H),5.15(dd,J＝7.9,6.4Hz,1H),4.16(p,J＝7.3Hz,4H),4.00(s,3H),3.47(dd,J＝17.0,8.1Hz,1H),3.25(dd,J＝17.0,6.2Hz,1H),1.22(t,J＝7.1Hz,3H),1.16(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝δ172.2,171.7,158.8,155.7,142.5,130.1,127.5,127.0,126.2,124.2,123.9,121.3,121.1,105.9,77.3,77.0,76.7,61.3,60.7,55.5,46.3,35.5,14.1,14.1.
high resolution: calculated values: [ M+H ]] + 382.1654, found: 382.1648.
example 5:
in a 10mL reaction flask, compound 1c (0.2 mmol,38.7 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to perform a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give the pure product as a yellow oil with 82% yield.
Compound 3ca was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝δ8.51(dd,J＝13.6,8.5Hz,2H),8.15–8.04(m,2H),7.64(dd,J＝15.2,7.7Hz,3H),5.21(t,J＝6.8Hz,1H),4.25–4.05(m,4H),3.44(dd,J＝16.8,8.3Hz,1H),3.22(dd,J＝16.9,5.4Hz,1H),2.61(s,3H),1.23(t,J＝7.2Hz,3H),1.15(t,J＝6.8Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝δ172.2,171.8,156.5,143.0,137.5,132.2,131.1,130.1,128.1,126.9,125.2,125.1,123.9,122.5,121.6,77.3,77.0,76.7,61.2,60.7,45.9,35.7,21.9,14.1,14.0.
high resolution: calculated values: [ M+H ]] + 366.1705, found: 366.1700.
example 6:
in a 10mL reaction flask, compound 1d (0.2 mmol,42.7 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to perform a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give the pure product as a yellow oil in 71% yield.
Compound 3da was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝δ8.56(d,J＝8.7Hz,1H),8.47(d,J＝8.0Hz,1H),8.35(s,1H),8.15–8.10(m,1H),7.81–7.61(m,3H),5.17–5.08(m,1H),4.15(dq,J＝13.0,6.5Hz,4H),3.44(dd,J＝17.0,7.6Hz,1H),3.30(dd,J＝17.0,6.3Hz,1H),1.22(t,J＝7.0Hz,3H),1.17(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝δ171.9,171.3,155.6,143.2,133.5,131.6,131.0,130.3,128.9,127.4,126.0,125.3,124.3,123.2,121.7,77.3,77.0,76.7,61.4,60.7,45.8,35.4,14.1,14.0.
high resolution: calculated values: [ M+H ]] + 386.1159, found: 386.1151.
example 7:
in a 10mL reaction flask, compound 1e (0.2 mmol,51.4 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to perform a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give pure product, yellow solid, 59% yield.
Compound 3ea was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝δ8.78–8.69(m,2H),8.52(d,J＝8.0Hz,1H),8.15(d,J＝7.8Hz,1H),8.01–7.99(m,1H),7.81(t,J＝7.5Hz,1H),7.71(t,J＝7.6Hz,1H),5.16(t,J＝7.2Hz,1H),4.23–4.09(m,4H),3.50–3.37(m,2H),1.22(t,J＝7.2Hz,3H),1.18(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝δ171.7,170.9,155.9,144.2,135.7,131.6,131.4,130.5,130.4,127.9,124.6,123.8,122.5,122.4,118.5,111.0,77.3,77.0,76.7,61.6,60.8,45.5,35.3,14.1,14.0.
melting point: 111-113 ℃.
High resolution: calculated values: [ M+H ]] + 377.1501, found: 377.1497.
example 8:
in a 10mL reaction flask, compound 1f (0.2 mmol,40.8 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to perform a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give pure product, yellow solid, 59% yield.
Compound 3fa was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝δ8.54–8.45(m,3H),8.10(dd,J＝8.1,1.1Hz,1H),7.91(dd,J＝8.8,1.9Hz,1H),7.76–7.69(m,1H),7.66–7.62(m,1H),5.13(s,1H),4.16(dq,J＝11.5,7.1Hz,4H),3.44(dd,J＝17.1,7.7Hz,1H),3.30(dd,J＝17.1,6.7Hz,1H),1.22(t,J＝7.1Hz,3H),1.17(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝δ171.9,171.3,155.5,143.2,133.7,131.9,130.4,129.0,128.5,127.4,126.3,124.4,123.2,121.7,121.6,77.3,77.0,76.7,61.5,60.7,45.8,35.4,14.1,14.0.
melting point: 161-163 ℃.
High resolution: calculated values: [ M+H ]] + 430.0654, found: 430.0636.
example 9:
in a 10mL reaction flask, compound 1f (0.2 mmol,39.4 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to perform a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give pure product as yellow oil with 42% yield.
Compound 3ga was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝δ8.62(dd,J＝9.1,5.4Hz,1H),8.46(dd,J＝8.2,1.2Hz,1H),8.11(dd,J＝8.1,1.1Hz,1H),8.01(dd,J＝10.0,2.6Hz,1H),7.74–7.53(m,3H),5.11–5.04(m,1H),4.23–4.05(m,4H),3.44(dd,J＝17.1,7.7Hz,1H),3.36–3.21(m,1H),1.22(t,J＝7.1Hz,3H),1.16(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝δ171.9,171.4,162.7,160.2,155.8,155.8,143.0,130.3,129.9,128.4,127.4,126.4,126.3,125.1,125.1,123.3,121.6,119.8,119.5,110.7,110.4,77.3,77.0,76.7,61.4,60.7,46.0,35.4,14.1,14.0.
high resolution: calculated values: [ M+H ]] + 370.1455, found: 370.1450.
example 10:
in a 10mL reaction flask, the compound 1h (0.2 mmol,39.4 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg) and methanol (1 mL) were added under nitrogen atmosphere to perform a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give pure product as yellow oil with 65% yield.
Compound 3ha was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝δ8.78–8.69(m,2H),8.57f–8.52(m,1H),8.16–8.14(m,1H),8.03(dd,J＝8.7,1.4Hz,1H),7.80–7.76(m,1H),7.69(td,J＝7.7,7.1,1.3Hz,1H),5.23(t,J＝7.2Hz,1H),4.22–4.10(m,4H),3.48(dd,J＝17.1,7.4Hz,1H),3.39(dd,J＝17.1,7.1Hz,1H),1.21(t,J＝7.1Hz,3H),1.15(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝δ171.9,171.2,156.4,144.0,135.4,130.5,129.8,129.4,129.0,127.6,126.3,126.3,125.4,124.5,123.6,122.9,122.6,122.2,77.3,77.0,76.7,61.6,60.8,45.7,35.3,14.1,13.9.
melting point: 68-70deg.C
High resolution: calculated values: [ M+H ]] + 420.1423, found: 420.1412.
example 11:
in a 10mL reaction flask, compound 1i (0.2 mmol,51.2 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to conduct a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give pure product, yellow solid, 48% yield.
Compound 3ia was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝δ8.72(d,J＝8.6Hz,1H),8.57(dd,J＝8.6,1.4Hz,2H),8.12(td,J＝8.8,1.6Hz,2H),7.77(dt,J＝8.2,1.7Hz,2H),7.74–7.62(m,2H),7.56–7.50(m,2H),7.46–7.42(m,1H),5.30(dd,J＝8.0,6.4Hz,1H),4.22–4.10(m,4H),3.49(dd,J＝17.0,8.1Hz,1H),3.28(dd,J＝17.0,6.3Hz,1H),1.21(t,J＝7.1Hz,3H),1.15(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝δ172.1,171.7,156.9,143.3,140.3,140.2,132.3,130.3,129.7,129.1,128.6,127.9,127.4,127.2,125.4,123.9,123.7,123.2,121.9,77.3,77.0,76.7,61.4,60.7,46.1,35.7,14.2,14.0.
melting point: 88-90 DEG C
High resolution: calculated values: [ M+H ]] + 428.1862, found: 428.1865.
example 12:
in a 10mL reaction flask, compound 1j (0.2 mmol,47.5 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to perform a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give pure product, yellow solid in 32% (50%).
Compound 3ja was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝δ9.12–9.11(d,J＝1.5Hz,1H),8.74–8.68(d,J＝8.6Hz,1H),8.58–8.56(m,1H),8.46(dd,J＝8.7,1.6Hz,1H),8.14(dd,J＝8.1,1.0Hz,1H),7.77(ddd,J＝8.2,7.1,1.4Hz,1H),7.68(ddd,J＝8.3,7.1,1.3Hz,1H),5.30(t,J＝7.3Hz,1H),4.18–4.11(m,5H),4.04(s,3H),3.46(dd,J＝17.1,7.6Hz,1H),3.34(dd,J＝17.1,6.9Hz,1H),1.21(t,J＝7.1Hz,3H),1.16(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝δ172.0,171.4,166.5,157.2,144.1,136.3,130.4,130.3,129.7,128.9,128.3,127.4,124.6,123.2,122.9,122.5,77.3,77.0,76.7,61.4,60.7,52.5,45.7,35.5,14.1,14.0.
melting point: 111-113 DEG C
High resolution: calculated values: [ M+H ]] + 410.1604, found: 410.1606.
example 13:
in a 10mL reaction flask, compound 1k (0.2 mmol,38.7 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to conduct a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give pure product, yellow solid, 69% yield.
Compound 3ka was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝δ8.63(d,J＝8.2Hz,1H),8.36–8.28(m,2H),8.00(d,J＝8.3Hz,1H),7.84–7.77(m,1H),7.69(ddd,J＝8.2,7.1,1.1Hz,1H),7.52(dd,J＝8.3,1.5Hz,1H),5.21(dd,J＝8.3,6.2Hz,1H),4.20–4.09(m,4H),3.44(dd,J＝17.0,8.3Hz,1H),3.22(dd,J＝17.0,6.1Hz,1H),2.60(s,3H),1.21(t,J＝7.1Hz,3H),1.14(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝δ172.1,171.8,155.8,141.7,136.9,133.0,130.2,130.2,129.9,127.3,125.7,124.9,123.6,122.5,121.4,77.3,77.0,76.7,61.2,60.6,46.0,35.6,21.9,14.1,14.0.
melting point: 69-71 DEG C
High resolution: calculated values: [ M+H ]] + 366.1705, found: 366.1700.
example 14:
in a 10mL reaction flask, 1l (0.2 mmol,39.4 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg) and methanol (1 mL) were added under nitrogen atmosphere to perform a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give pure product, yellow solid, 67% yield.
Compound 3la was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝δ8.52(d,J＝8.2Hz,1H),8.36(d,J＝8.2Hz,1H),8.17–8.06(m,2H),7.85(ddd,J＝8.3,7.2,1.2Hz,1H),7.76(ddd,J＝8.2,7.1,1.1Hz,1H),7.43(ddd,J＝8.9,8.1,2.7Hz,1H),5.21(dd,J＝7.9,6.5Hz,1H),4.20–4.11(m,4H),3.43(dd,J＝17.0,8.0Hz,1H),3.25(dd,J＝17.0,6.4Hz,1H),1.22(t,J＝7.1Hz,3H),1.15(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝δ172.0,171.7,162.6,160.2,156.0,140.2,132.7,132.7,132.5,132.4,130.6,128.2,125.9,125.2,125.1,125.0,122.7,117.6,117.3,106.9,106.7,77.3,77.0,76.7,61.3,60.7,45.9,35.6,14.1,14.0.
melting point: 66-68 DEG C
High resolution: calculated values: [ M+H ]] + 370.1455, found: 370.1447.
example 15:
in a 10mL reaction flask, compound 1m (0.2 mmol,49.4 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to conduct a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give pure product, yellow solid, 55% yield.
Compound 3ma was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝8.82(s,1H),8.69(d,J＝8.2Hz,1H),8.41(d,J＝8.2Hz,1H),8.22(d,J＝8.5Hz,1H),7.94–7.89(m,2H),7.82–7.78(m,1H),5.25(t,J＝7.2Hz,1H),4.20–4.10(m,4H),3.43(dd,J＝17.0,7.7Hz,1H),3.30(dd,J＝17.0,6.7Hz,1H),1.21(t,J＝7.1Hz,3H),1.15(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝171.9,171.4,159.3,144.7,132.9,131.2,131.1,128.4,126.1,125.3,124.6,124.6,123.5,122.6,119.8,119.7,77.3,77.0,76.7,61.5,60.8,46.1,35.5,14.1,14.0.
melting point: 100-102 DEG C
High resolution: calculated values: [ M+H ]] + 420.1423, found: 420.1415.
example 16:
in a 10mL reaction flask, compound 1N (0.2 mmol,42.7 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to perform a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give pure product, yellow solid, yield 70%.
Compound 3na was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝8.55(d,J＝8.2Hz,1H),8.48(d,J＝2.1Hz,1H),8.36(d,J＝8.2Hz,1H),8.03(d,J＝8.7Hz,1H),7.85(t,J＝7.6Hz,1H),7.75(t,J＝7.6Hz,1H),7.63(dd,J＝8.7,2.2Hz,1H),5.23–5.19(m,1H),4.20–4.10(m,4H),3.42(dd,J＝17.0,7.9Hz,1H),3.25(dd,J＝17.0,6.5Hz,1H),1.21(t,J＝7.1Hz,3H),1.15(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝172.0,171.5,157.1,141.7,132.9,132.2,131.7,130.8,129.1,128.2,125.9,125.1,124.9,122.6,121.5,77.3,77.0,76.7,61.4,60.7,46.0,35.5,14.1,14.0.
melting point: 61-63 DEG C
High resolution: calculated values: [ M+H ]] + 386.1159, found: 386.1153.
example 17:
in a 10mL reaction flask, compound 1o (0.2 mmol,39.4 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to conduct a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give pure product, yellow solid, yield 44%.
Compound 3oa was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝8.98–8.93(m,1H),8.23–8.10(m,2H),7.77–7.64(m,3H),7.56(ddd,J＝13.2,7.9,1.0Hz,1H),5.23–5.17(m,1H),4.16(dtd,J＝9.6,7.2,5.5Hz,4H),3.42(dd,J＝17.0,7.8Hz,1H),3.27–3.25(m,1H),1.22(t,J＝7.1Hz,3H),1.15(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝172.0,171.5,162.2,159.7,156.0,156.0,143.6,130.2,128.9,128.8,127.7,127.6,127.6,127.6,127.3,127.3,126.9,126.7,122.6,122.5,121.7,121.7,121.5,121.4,117.2,117.0,77.3,77.0,76.7,61.4,60.7,46.4,35.6,14.1,14.0.
melting point: 71-73 DEG C
High resolution: calculated values: [ M+H ]] + 370.1455, found: 370.1450.
example 18:
in a 10mL reaction flask, compound 1p (0.2 mmol,41.8 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to perform a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give the pure product as a yellow oil with 53% yield.
Compound 3pa was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝9.47(d,J＝8.4Hz,1H),8.11(d,J＝7.9Hz,1H),7.97(d,J＝8.3Hz,1H),7.66–7.61(m,3H),7.34(d,J＝8.0Hz,1H),5.20(dd,J＝8.1,6.2Hz,1H),4.19–4.11(m,7H),3.40(dd,J＝16.9,8.2Hz,1H),3.22(dd,J＝17.0,6.1Hz,1H),1.22(t,J＝7.1Hz,3H),1.15(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝172.1,172.0,158.6,156.4,143.8,130.0,127.9,127.8,127.7,127.0,126.8,123.8,123.6,117.9,111.5,77.3,77.0,76.7,61.2,60.7,55.8,46.7,35.8,14.2,14.0.
high resolution: calculated values: [ M+H ]] + 382.1654, found: 382.1649.
example 19:
in a 10mL reaction flask, compound 1q (0.2 mmol,39.4 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to perform a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give pure product as yellow oil with 55% yield.
Compound 3qa was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝8.59(d,J＝8.3Hz,1H),8.52(dd,J＝9.1,5.8Hz,1H),8.36(d,J＝8.3Hz,1H),7.86(t,J＝7.3Hz,1H),7.79–7.70(m,2H),7.40(td,J＝8.6,2.7Hz,1H),5.24–5.20(m,1H),4.21–4.11(m,4H),3.41(dd,J＝17.0,7.9Hz,1H),3.25(dd,J＝17.0,6.5Hz,1H),1.22(t,J＝7.1Hz,3H),1.15(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝172.0,171.6,163.8,161.4,158.3,144.7,144.6,133.0,130.9,127.4,126.0,124.6,123.9,123.8,122.4,120.5,116.2,116.0,114.8,114.6,77.3,77.0,76.7,61.4,60.8,46.0,35.6,14.2,14.0.
high resolution: calculated values: [ M+H ]] + 370.1455, found: 370.1448.
example 20:
in a 10mL reaction flask, compound 1r (0.2 mmol,49.4 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to conduct a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give pure product, yellow solid, 65% yield.
Compound 3ra was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝8.66(dd,J＝12.7,8.5Hz,2H),8.42(d,J＝7.4Hz,2H),7.92(t,J＝7.6Hz,1H),7.85–7.80(m,2H),5.24(t,J＝7.2Hz,1H),4.20–4.09(m,4H),3.43(dd,J＝17.1,7.6Hz,1H),3.31(dd,J＝17.0,6.8Hz,1H),1.22(t,J＝7.1Hz,3H),1.15(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝171.9,171.4,158.5,142.6,132.4,131.1,130.6,130.3,128.7,127.7,127.7,126.1,126.1,125.6,123.0,122.9,122.9,77.3,77.0,76.7,61.5,60.8,46.0,35.5,14.1,14.0.
melting point: 112-114 DEG C
High resolution: calculated values: [ M+H ]] + 420.1423, found: 420.1413.
example 21:
in a 10mL reaction flask, compound 1s (0.2 mmol,38.9 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), ethyl diazoacetate 2a (1 mmol,114.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to conduct a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give the pure product as a yellow oil with a yield of 50%.
Compound 3sa was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝8.60(d,J＝8.3Hz,1H),8.42(d,J＝8.4Hz,1H),8.33(d,J＝8.3Hz,1H),7.92(s,1H),7.81(t,J＝7.4Hz,1H),7.68(t,J＝7.4Hz,1H),7.48–7.45(m,1H),5.21(dd,J＝8.2,6.2Hz,1H),4.22–4.09(m,4H),3.44(dd,J＝17.0,8.3Hz,1H),3.21(dd,J＝17.0,6.1Hz,1H),2.57(s,3H),1.21(t,J＝7.1Hz,3H),1.14(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝172.1,171.8,156.8,143.5,138.7,133.3,130.4,129.7,128.7,127.0,125.7,124.6,122.4,121.6,121.4,77.3,77.0,76.7,61.2,60.7,46.0,35.7,21.4,14.1,14.0.
high resolution: calculated values: [ M+H ]] + 366.1705, found: 366.1697.
example 22:
in a 10mL reaction flask, compound 1a (0.2 mmol,35.8 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), methyl diazoacetate 2b (1 mmol,100.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg), and methanol (1 mL) were added under nitrogen atmosphere to perform a reaction under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give the pure product as a yellow oil with 69% yield.
Compound 3ab was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝8.64(d,J＝8.2Hz,1H),8.53(d,J＝7.7Hz,1H),8.34(d,J＝8.2Hz,1H),8.13–8.10(m,1H),7.86–7.82(m,1H),7.75–7.61(m,3H),5.26(dd,J＝8.0,6.4Hz,1H),3.68(d,J＝5.5Hz,6H),3.48(dd,J＝17.1,8.1Hz,1H),3.27(dd,J＝17.1,6.2Hz,1H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝172.5,172.2,156.6,143.3,133.2,130.5,130.2,128.6,127.6,127.1,125.6,124.9,123.8,122.6,121.8,77.3,77.0,76.7,52.5,51.9,45.7,35.4.
high resolution: calculated values: [ M+H ]] + 324.1236, found: 324.1210.
example 23:
in a 10mL reaction flask, compound 1a (0.2 mmol,35.8 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), propyl diazoacetate 2b (1 mmol,128.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg) and methanol (1 mL) were added under nitrogen atmosphere to react under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give the pure product as a yellow oil with a yield of 64%.
Compound 3ac was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝8.64(d,J＝8.3Hz,1H),8.53(d,J＝8.0Hz,1H),8.37(d,J＝8.2Hz,1H),8.12–8.10(m,1H),7.85–7.81(m,1H),7.73–7.61(m,3H),5.25(dd,J＝7.9,6.5Hz,1H),4.06(dtd,J＝12.8,6.5,3.0Hz,4H),3.47(dd,J＝17.1,8.1Hz,1H),3.28(dd,J＝17.1,6.3Hz,1H),1.56(ddq,J＝33.1,14.0,7.2Hz,4H),0.88(t,J＝7.4Hz,3H),0.73(t,J＝7.4Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝172.1,171.8,156.8,143.3,133.2,130.4,130.2,128.5,127.4,126.9,125.8,124.9,123.7,122.5,121.8,77.3,77.0,76.7,66.8,66.3,46.0,35.6,21.9,21.8,10.3,10.1.
high resolution: calculated values: [ M+H ]] + 380.1862, found: 380.1833.
example 24:
in a 10mL reaction flask, compound 1a (0.2 mmol,35.8 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), isopropyl diazoacetate 2b (1 mmol,128.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg) and methanol (1 mL) were added under nitrogen atmosphere to react under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give the pure product as a yellow oil with a yield of 72%.
Compound 3ad was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝8.63(d,J＝8.2Hz,1H),8.56–8.50(m,1H),8.34(d,J＝8.2Hz,1H),8.15–8.06(m,1H),7.86–7.79(m,1H),7.74–7.59(m,3H),5.18(dd,J＝8.1,6.5Hz,1H),5.04(dh,J＝25.0,6.2Hz,2H),3.37(dd,J＝16.9,8.2Hz,1H),3.20(dd,J＝16.9,6.4Hz,1H),1.23–1.16(m,9H),1.10(d,J＝6.2Hz,3H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝171.5,171.3,157.0,143.3,133.2,130.4,130.1,128.5,127.4,126.9,125.8,124.9,123.7,122.5,121.8,77.3,77.0,76.7,68.7,68.0,46.4,35.9,21.7,21.6,21.4.
high resolution: calculated values: [ M+H ]] + 380.1862, found: 380.18634.
example 25:
in a 10mL reaction flask, compound 1a (0.2 mmol,35.8 mg), eosin Y disodium salt (0.006mmol, 4.2 mg), benzyl diazoacetate 2b (1 mmol,176.1 mg), N-diisopropylethylamine (0.2 mmol,25.8 mg) and methanol (1 mL) were added under nitrogen atmosphere to react under blue light irradiation. After TLC (thin layer chromatography) detected that the reaction was complete, the organic solvent was removed under reduced pressure, and [ V (petroleum ether): v (ethyl acetate) =10:1-5:1, the present example is preferably V (petroleum ether): v (ethyl acetate) =7:1 ], to give pure product as yellow oil with 42% yield.
Compound 3ab was tested:
1 H NMR(400MHz,CDCl 3 ,300K):δ(ppm)＝8.64(d,J＝8.3Hz,1H),8.53(d,J＝8.0Hz,1H),8.29(d,J＝8.3Hz,1H),8.05(d,J＝7.9Hz,1H),7.82(t,J＝7.6Hz,1H),7.66(ddd,J＝11.8,9.0,6.9Hz,3H),7.29–7.10(m,10H),5.31(t,J＝7.2Hz,1H),5.19–5.06(m,4H),3.51(dd,J＝17.1,7.8Hz,1H),3.38(dd,J＝17.1,6.6Hz,1H).
13 C NMR(100MHz,CDCl 3 ,300K):δ(ppm)＝171.8,171.5,156.5,143.3,135.8,135.6,133.3,130.5,130.3,128.6,128.4,128.3,128.1,128.0,128.0,127.8,127.5,127.1,125.7,124.9,123.8,122.6,121.8,77.3,77.0,76.7,66.9,66.5,46.0,35.6.
high resolution: calculated values: [ M+H ]] + 476.1862, found: 476.1851.
Claims (2)
1. a synthesis method of a benzanthridine derivative is characterized by comprising the following steps of:
firstly, generating an excited state photocatalyst eosin Y disodium salt by the photocatalyst eosin Y disodium salt under the illumination condition, and then generating alkyl free radicals by single electron transfer between a diazonium compound 2 and the excited state photocatalyst eosin Y disodium salt; adding biphenyl isocyanic acid compound 1 into alkyl free radical to obtain imine free radical, and then carrying out intramolecular cyclization, oxidation and deprotonation to obtain benzanthracene derivative 3;
the synthetic route is as follows:
substituent R in Compound 1 1 Is methyl, methoxy, cyano, trifluoromethyl, phenyl, methoxycarbonyl or halogen, and the substituent R 2 Methyl, methoxy, cyano, trifluoromethyl, phenyl, methoxycarbonyl or halogen;
substituent R in Compound 2 3 Is methyl, ethyl, n-propyl, isopropyl or benzyl.
2. The synthesis method according to claim 1, wherein:
after the reaction is finished, separating and purifying to obtain a target product; the separation and purification are carried out by silica gel column chromatography, the eluent is petroleum ether and ethyl acetate, and the volume ratio is 10:1-5:1.
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| CN110317170A (en) * | 2019-08-02 | 2019-10-11 | 淮北师范大学 | A kind of green synthesis method of 3- phenanthridinyl propyl formate class compound |
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| CN110317170A (en) * | 2019-08-02 | 2019-10-11 | 淮北师范大学 | A kind of green synthesis method of 3- phenanthridinyl propyl formate class compound |
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| Title |
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| Hai-Bing Ye等.Photochemical Synthesis of Succinic Ester-Containing Phenanthridines from Diazo Compounds as 1,4-Dicarbonyl Precursors.《Org. Lett.》.2022,第24卷第6018-6023页. * |
| Photocatalytic xanthate-based radical addition/ cyclization reaction sequence toward 2-biphenyl isocyanides: synthesis of 6-alkylated phenanthridines;Pedro López-Mendoza等;《Org. Biomol. Chem.》;第18卷;第3487-3491页 * |
| 光促进６－三氟甲基－菲啶衍生物的合成;杨晓博等;《沈阳师范大学学报（自然科学版）》;第37卷(第2期);第126-133页 * |
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