CN111689921A - Preparation method of naphtho-dihydrooxazine compound - Google Patents
Preparation method of naphtho-dihydrooxazine compound Download PDFInfo
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- CN111689921A CN111689921A CN201910199216.8A CN201910199216A CN111689921A CN 111689921 A CN111689921 A CN 111689921A CN 201910199216 A CN201910199216 A CN 201910199216A CN 111689921 A CN111689921 A CN 111689921A
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- naphtho
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- dihydrooxazine
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- naphthol
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- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000002841 Lewis acid Substances 0.000 claims abstract description 8
- 229950011260 betanaphthol Drugs 0.000 claims abstract description 8
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 8
- 239000003504 photosensitizing agent Substances 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 150000002332 glycine derivatives Chemical class 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 239000012298 atmosphere Substances 0.000 claims description 9
- -1 4-n-butoxy Chemical group 0.000 claims description 8
- 238000004440 column chromatography Methods 0.000 claims description 8
- 229940125782 compound 2 Drugs 0.000 claims description 6
- IICCLYANAQEHCI-UHFFFAOYSA-N 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 IICCLYANAQEHCI-UHFFFAOYSA-N 0.000 claims description 5
- 229930187593 rose bengal Natural products 0.000 claims description 5
- 229940081623 rose bengal Drugs 0.000 claims description 5
- STRXNPAVPKGJQR-UHFFFAOYSA-N rose bengal A Natural products O1C(=O)C(C(=CC=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 STRXNPAVPKGJQR-UHFFFAOYSA-N 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 claims description 4
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 4
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 4
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims description 4
- ZBQZBWKNGDEDOA-UHFFFAOYSA-N eosin B Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC([N+]([O-])=O)=C(O)C(Br)=C1OC1=C2C=C([N+]([O-])=O)C(O)=C1Br ZBQZBWKNGDEDOA-UHFFFAOYSA-N 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 3
- VYXSBFYARXAAKO-WTKGSRSZSA-N chembl402140 Chemical compound Cl.C1=2C=C(C)C(NCC)=CC=2OC2=C\C(=N/CC)C(C)=CC2=C1C1=CC=CC=C1C(=O)OCC VYXSBFYARXAAKO-WTKGSRSZSA-N 0.000 claims description 3
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 3
- 229940045803 cuprous chloride Drugs 0.000 claims description 3
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 claims description 3
- YKYIFUROKBDHCY-ONEGZZNKSA-N (e)-4-ethoxy-1,1,1-trifluorobut-3-en-2-one Chemical group CCO\C=C\C(=O)C(F)(F)F YKYIFUROKBDHCY-ONEGZZNKSA-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
- 229940125904 compound 1 Drugs 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 claims description 2
- 229940043267 rhodamine b Drugs 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 239000003054 catalyst Substances 0.000 abstract description 3
- 230000004071 biological effect Effects 0.000 abstract description 2
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract 3
- 229910000510 noble metal Inorganic materials 0.000 abstract 1
- 239000007800 oxidant agent Substances 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- OELZFJUWWFRWLC-UHFFFAOYSA-N oxazine-1 Chemical compound C1=CC(N(CC)CC)=CC2=[O+]C3=CC(N(CC)CC)=CC=C3N=C21 OELZFJUWWFRWLC-UHFFFAOYSA-N 0.000 description 7
- 239000003208 petroleum Substances 0.000 description 7
- 230000003595 spectral effect Effects 0.000 description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- TZJRPKDPYLAMJZ-UHFFFAOYSA-N ethyl 2-(4-methoxyanilino)acetate Chemical compound CCOC(=O)CNC1=CC=C(OC)C=C1 TZJRPKDPYLAMJZ-UHFFFAOYSA-N 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- QEIUZMNIDXVOHV-UHFFFAOYSA-N 2-(4-ethoxyanilino)acetic acid Chemical compound CCOC1=CC=C(NCC(O)=O)C=C1 QEIUZMNIDXVOHV-UHFFFAOYSA-N 0.000 description 1
- KAUQJMHLAFIZDU-UHFFFAOYSA-N 6-Hydroxy-2-naphthoic acid Chemical compound C1=C(O)C=CC2=CC(C(=O)O)=CC=C21 KAUQJMHLAFIZDU-UHFFFAOYSA-N 0.000 description 1
- YLDFTMJPQJXGSS-UHFFFAOYSA-N 6-bromo-2-naphthol Chemical compound C1=C(Br)C=CC2=CC(O)=CC=C21 YLDFTMJPQJXGSS-UHFFFAOYSA-N 0.000 description 1
- WKTNIBWKHNIPQR-UHFFFAOYSA-N 6-hydroxynaphthalene-2-carbonitrile Chemical compound C1=C(C#N)C=CC2=CC(O)=CC=C21 WKTNIBWKHNIPQR-UHFFFAOYSA-N 0.000 description 1
- UNFNRIIETORURP-UHFFFAOYSA-N 7-methoxynaphthalen-2-ol Chemical compound C1=CC(O)=CC2=CC(OC)=CC=C21 UNFNRIIETORURP-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- 238000006683 Mannich reaction Methods 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- CPDRCKWKDRDHPW-UHFFFAOYSA-N boric acid;naphthalene Chemical compound OB(O)O.C1=CC=CC2=CC=CC=C21 CPDRCKWKDRDHPW-UHFFFAOYSA-N 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- VRAKZEPUJJPIIY-UHFFFAOYSA-N methyl 2-(4-methoxyanilino)acetate Chemical compound COC(=O)CNC1=CC=C(OC)C=C1 VRAKZEPUJJPIIY-UHFFFAOYSA-N 0.000 description 1
- 229910052755 nonmetal Inorganic materials 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
- C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
Abstract
The naphtho-dihydrooxazine compound has wide biological activity, is an important intermediate in medicine synthesis, can be used for synthesizing various medicine molecules with naphtho-dihydrooxazine frameworks, and has high potential medicine application value. The invention provides a simple and direct preparation method of a naphtho-dihydrooxazine compound catalyzed by visible light, which comprises the following steps: sequentially adding the glycine derivative, the 2-naphthol, the organic photosensitizer and the Lewis acid into a solvent, reacting for 36 hours at room temperature under the irradiation of visible light, and separating and purifying to obtain the product. Compared with the prior art, the method has the advantages of simple steps, cheap and easily-obtained raw materials, no use of noble metal catalysts and oxidants, mild conditions, environmental friendliness, high yield and the like, and has better industrial application prospect.
Description
Technical Field
The invention belongs to the field of organic preparation, and relates to a preparation method of a naphtho-dihydrooxazine compound.
Background
The naphtho-dihydrooxazine compound has potential biological and pharmacological activity and is a core structure of a plurality of bioactive molecules; also important as intermediates for the synthesis of pharmaceutically active molecules, for example, they can be used in the synthesis of analgesics, antibacterial agents, anticancer drugs, anti-HIV drugs, anti-ulcer drugs. In addition, certain dihydrooxazines have important research value as photochromic molecules. Therefore, the synthesis research of the naphtho-dihydrooxazine compound has important application value in the fields of drug development and preparation.
At present, the commonly used synthetic method of the naphtho-dihydrooxazine compound mostly adopts three-component Mannich reaction of naphthol, formaldehyde and arylamine compound.
In 2009, Nath et al successfully synthesized naphtho-dihydrooxazine compounds by a three-component "one-pot" reaction with naphthol, formaldehyde and aniline at room temperature (Journal of Heterocyclic Chemistry,2009,46, 1003).
In 2012, Tae et al obtained naphthodihydrooxazine compounds under ultrasonic irradiation with boron trifluoride supported on silica as catalyst (Journal of Chemical Research,2012,36, 398).
In 2013, Narentran et al dissolved 2-naphthol, aniline, formaldehyde in glycerol and reacted at 90 ℃ for 10min to obtain naphtho-dihydrooxazine compounds (Synthesis, 2013,45,1564) with a yield of 68%.
In 2017, Liu et al used naphthalene boric acid, formaldehyde and aniline as raw materials, and reacted at 120 ℃ under the catalysis of iridium to obtain naphtho-dihydrooxazine compounds, wherein the yield is 58% (Tetrahedron, 2017, 73, 3031).
In general, although the methods have high atom utilization rate, the methods generally have the defects of harsh reaction conditions, high cost, low yield, limited application range and the like. Particularly, the use of formaldehyde does not meet the aim of green chemistry, and is easy to diffuse into the air, thereby causing harm to human health and environment. The invention provides a novel method for green and efficient synthesis of naphtho-dihydrooxazine compounds by using visible light as an energy source, using a non-metal photosensitizer and Lewis acid as catalysts and using glycine derivatives and 2-naphthol as substrates.
Disclosure of Invention
The invention aims to provide a synthetic method of a naphtho-dihydro-oxazine derivative, which has the advantages of mild reaction conditions, environmental protection, simplicity, high efficiency and low cost.
The specific technical scheme is as follows: mixing glycine derivatives 1, 2-naphthol 2, a photosensitizer and Lewis acid shown in the formula I with a solvent under the air atmosphere and room temperature, reacting for 36 hours under visible light, and carrying out column chromatography to obtain the naphtho-dihydrooxazine compound.
The reaction equation is as follows:
wherein R is1May be 4-phenyl, 4-benzyl, 4-methoxy, 4-ethoxy, 4-isopropyl, 4-n-butoxy, 4-phenoxy, 4-benzyloxy, 2, 5-dimethoxy, etc., R2Can be methyl, ethyl, isopropyl, tert-butyl, benzyl, etc., R3May be 6-bromo, 7-bromo, 6-methoxy, 7-methoxy, 6-carboxy, 6-methyl formate, 6-cyano, 7-ethoxy, 7-hydroxy, etc.
The photosensitizer in the above steps is preferably one of rhodamine B, rhodamine 6G, eosin Y, eosin B and rose bengal, and the amount of the photosensitizer is 1-5 mol% of the compound 2.
In the above step, the Lewis acid is preferably one of copper sulfate, copper trifluoromethanesulfonate, copper bromide and cuprous chloride, and the amount of the Lewis acid is 5-20 mol% of the compound 2.
The solvent in the above step is preferably one of acetonitrile, toluene, ethyl acetate and 1, 2-dichloroethane.
The light source in the above step is preferably one of a 5W blue LED lamp and a 26W energy-saving lamp.
The amount of compound 1 used in the above step is preferably 2.5 times equivalent to that of compound 2.
Detailed Description
The following embodiments are further detailed for the present invention, but the scope of the present invention is not limited to these examples. The starting materials used in the present invention are either commercially available or can be prepared by methods known in the art.
Example 1
522mg (2.5mmol) of ethyl N- (4-methoxyphenyl) glycinate, 144mg (1.0mmol) of 2-naphthol, 10.1mg (1 mol%) of rose bengal, 22.3mg (10 mol%) of copper bromide and 30mL of 1, 2-dichloroethane are sequentially added into a 100mL round-bottomed flask under the conditions of air atmosphere and room temperature, and reacted for 36h under the irradiation of 5W LED blue light, and a column is usedChromatography (petroleum ether: ethyl acetate ═ 8:1) afforded diethyl 2- (4-methoxyphenyl) -2, 3-dihydro-1 h-naphthol [1,2-e ] as a pale red liquid][1,3]Oxazine-1, 3-dicarboxylic acid in 79% yield, spectral data:1H NMR(400MHz,CDCl3)：7.78(dd,J＝8.4,4.5Hz,2H),7.67(d,J＝8.4Hz,1H),7.46(d,J＝1.3Hz,1H),7.39–7.34(m,1H),7.32(d,J＝9.0 Hz,1H),7.25–7.19(m,2H),6.77–6.69(m,2H),6.28(s,1H),5.24(s,1H),4.43–4.25(m,2H), 4.22–4.10(m,2H),3.70(s,3H),1.34(t,J＝7.1Hz,3H),1.11(t,J＝7.1Hz,3H).13CNMR(100 MHz,CDCl3):171.2,166.1,157.4,151.8,140.1,131.2,129.9,129.5,128.8,127.1,126.3,124.0, 121.6,119.1,114.2,110.4,83.2,63.7,61.8,61.7,55.3,14.1,13.9.
example 2
557mg (2.5mmol) of N- (4-ethoxyphenyl) glycine ethyl ester, 144mg (1.0mmol) of 2-naphthol, 4.8mg (1 mol%) of rhodamine 6G, 24.9mg of copper sulfate and 30mL of acetonitrile are sequentially added into a 100mL round-bottomed flask under the condition of air atmosphere and room temperature, the mixture reacts for 36 hours under the radiation of 5W LED blue light, and column chromatography (petroleum ether: ethyl acetate: 8:1) is carried out to obtain light yellow liquid diethyl 2- (4-ethoxyphenyl) -2, 3-dihydro-1 hydrogen-naphthol [1,2-e ] of][1,3]Oxazine-1, 3-dicarboxylic acid in 82% yield, spectral data:1H NMR(400MHz,CDCl3)：7.77(dd,J＝8.3,5.3Hz,2H), 7.67(d,J＝8.4Hz,1H),7.45(t,J＝7.6Hz,1H),7.40–7.29(m,2H),7.21(d,J＝8.9Hz,2H), 6.72(d,J＝8.9Hz,2H),6.27(s,1H),5.24(s,1H),4.44–4.25(m,2H),4.24–4.09(m,2H),3.92(q, J＝7.0Hz,2H),1.34(t,J＝7.0Hz,6H),1.10(t,J＝7.1Hz,3H).13C NMR(100MHz,CDCl3):171.2,166.1,156.8,151.9,139.9,131.3,129.9,129.5,128.8,127.1,126.4,124.0,121.7,119.2, 114.8,110.5,83.2,63.7,63.5，61.8，61.7,14.7,14.1,13.9.
example 3
487.5mg (2.5mmol) of N- (4-methoxyphenyl) glycine methyl ester, 144mg (1.0mmol) of 2-naphthol, 10.1mg (1 mol%) of rose bengal, 36.2mg (10 mol%) of copper trifluoromethanesulfonate and 30mL of ethyl acetate were sequentially added to a 100mL round-bottomed flask under an air atmosphere at room temperature, reacted for 36 hours under the irradiation of a 26W energy-saving lamp, and column chromatography (petroleum ether: ethyl acetate: 8:1) was performed to obtain dimethyl 2- (4-methoxyphenyl) -2, 3-dihydro-1 h-naphthol [1,2-e ] as a white solid][1,3]Oxazine-1, 3-dicarboxylic acid, at a yield of 79%, with spectral data:1H NMR(400MHz,CDCl3)： 7.81(dd,J＝8.4,4.1Hz,2H),7.66(d,J＝8.3Hz,1H),7.52–7.46(m,1H),7.40(t,J＝7.1Hz, 1H),7.34(d,J＝8.9Hz,1H),7.26–7.19(m,2H),6.78–6.73(m,2H),6.31(s,1H),5.30(s,1H), 3.90(s,3H),3.74(s,6H).13C NMR(100MHz,CDCl3):166.5,157.4,151.8,139.9,131.2,130.1, 129.5,128.9,127.3,126.1,124.1,121.5,119.1,114.3,110.3,83.2,63.6,55.3,52.9,52.7.
example 4
522mg (2.5mmol) of ethyl N- (4-methoxyphenyl) glycinate, 169mg (1.0mmol) of 6-cyano 2-naphthol, 10.1mg (1 mol%) of rose bengal, 9.9mg (10 mol%) of cuprous chloride and 30mL of ethyl acetate are sequentially added to a 100mL round-bottomed flask, and the mixture is reacted for 36 hours under the irradiation of 5W LED blue light, and column chromatography (petroleum ether: ethyl acetate ═ 8:1) is carried out to obtain diethyl 8-cyano-2- (4-methoxyphenyl) -2, 3-dihydro-1 h-naphthol [1,2-e ] as a pale yellow solid under the conditions of air atmosphere and room temperature][1,3]Oxazine-1, 3-dicarboxylic acid, at a yield of 77%, and spectral data:1H NMR(400MHz, CDCl3)：8.15(d,J＝1.4Hz,1H),7.82(d,J＝9.1Hz,1H),7.75(d,J＝8.8Hz,1H),7.59(dd,J＝ 8.8,1.7Hz,1H),7.43(d,J＝9.0Hz,1H),7.23–7.17(m,2H),6.78–6.72(m,2H),6.29(s,1H),5.23(s,1H),4.44–4.30(m,2H),4.25–4.11(m,2H),3.72(s,3H),1.35(t,J＝7.1Hz,3H),1.10(t, J＝7.1Hz,3H).13C NMR(100MHz,CDCl3)：170.7,165.5,157.6,154.3,139.6,134.5,133.1, 130.4,128.5,127.8,126.2,122.9,121.2,119.0,114.3,110.8,107.4,83.4,63.4,62.1,62.0,55.3, 14.1,13.8.
example 5
522mg (2.5mmol) of ethyl N- (4-methoxyphenyl) glycinate, 174mg (1.0mmol) of 7-methoxy-2-naphthol, 6.9mg (1 mol%) of eosin Y, 24.9mg of copper sulfate and 30mL of toluene are sequentially added into a 100mL round-bottomed flask under the condition of air atmosphere and room temperature, and reacted for 36 hours under the irradiation of 5W LED blue light, and column chromatography (petroleum ether: ethyl acetate: 8:1) is carried out to obtain diethyl 9-methoxy-2- (4-methoxyphenyl) -2, 3-dihydro-1 hydro-naphthol [1,2-e ] as a white solid][1,3]Oxazine-1, 3-dicarboxylic acid in 74% yield, spectral data:1H NMR(400MHz,CDCl3):7.68(dd,J＝ 8.9,4.9Hz,2H),7.25–7.20(m,2H),7.17(dd,J＝8.9,2.6Hz,2H),6.97(d,J＝2.2Hz,1H),6.74(d,J＝9.0Hz,2H),6.30(s,1H),5.15(s,1H),4.34(dd,J＝11.1,7.1Hz,2H),4.25–4.11(m,2H),3.86(s,3H),3.71(s,3H),1.34(t,J＝7.1Hz,3H),1.11(t,J＝7.1Hz,3H).13C NMR(100MHz, CDCl3):171.3,166.2,158.8,157.5,152.5,140.1,132.5,130.3,129.6,129.4,126.5,124.7,116.6, 116.5,116.1,114.2,109.5,101.1,83.2,63.9,61.8,55.4,55.2,14.2,13.9.
example 6
522mg (2.5mmol) of ethyl N- (4-methoxyphenyl) glycinate, 174mg (1.0mmol) of 2-hydroxy-6-naphthoic acid, 6.9mg (1 mol%) of eosin B, 36.2mg (10 mol%) of copper trifluoromethanesulfonate and 30mL of acetonitrile are successively added to a 100mL round-bottomed flask under the irradiation of 5W LED blue light for reaction for 36h, and column chromatography (petroleum ether: ethyl acetate: 8:1) is carried out to obtain pale yellow solid diethyl 8-carboxy-2- (4-methoxyphenyl) -2, 3-dihydro-1 h-naphthyl [1,2-e ] under the conditions of air atmosphere and room temperature][1,3]Oxazine-1, 3-dicarboxylic acid, at 69% yield, and spectral data:1H NMR(400MHz, CDCl3)：8.62(d,J＝1.6Hz,1H),8.10(dd,J＝8.9,1.7Hz,1H),7.91(d,J＝9.1Hz,1H),7.74(d, J＝8.9Hz,1H),7.40(d,J＝9.0Hz,1H),7.25–7.18(m,2H),6.77–6.72(m,2H),6.31(s,1H),5.27(s,1H),4.42–4.30(m,2H),4.24–4.12(m,2H),3.72(s,3H),1.35(t,J＝7.1Hz,3H),1.11(t, J＝7.1Hz,3H).13C NMR(100MHz,CDCl3):171.8,170.9,165.8,157.5,154.1,139.8,134.3, 132.7,131.5,128.6,126.8,126.3,124.7,122.1,120.3,114.3,110.7,83.3,63.5,62.0,61.9,55.4, 14.2,13.9.
example 7
522mg (2.5mmol) of ethyl N- (4-methoxyphenyl) glycinate, 223mg (1.0mmol) of 6-bromo-2-naphthol, 6.9mg (1 mol%) of eosin B, 22.3mg (10 mol%) of copper bromide and 30mL of 1, 2-dichloroethane are sequentially added to a 100mL round-bottomed flask under an air atmosphere at room temperature, reacted for 36 hours under the irradiation of a 26W energy-saving lamp, and subjected to column chromatography (petroleum ether: ethyl acetate: 8:1) to obtain diethyl 8-bromo-2- (4-methoxyphenyl) -2, 3-dihydro-1-hydro-naphthyl [1,2-e ] to obtain a white solid][1,3]Oxazine-1, 3-dicarboxylic acid, at a yield of 76%, and spectral data:1H NMR(400MHz,CDCl3)：7.95 (d,J＝1.8Hz,1H),7.69(d,J＝9.0Hz,1H),7.55(dt,J＝9.0,5.5Hz,2H),7.36(d,J＝9.0Hz,1H),7.26–7.19(m,2H),6.79–6.73(m,2H),6.29(s,1H),5.23(s,1H),4.44–4.30(m,2H),4.25–4.15(m,2H),3.74(s,3H),1.36(t,J＝7.1Hz,3H),1.13(t,J＝7.1Hz,3H).13C NMR(100MHz,CDCl3):170.9,165.9,157.5,152.1,139.9,130.7,130.2,129.8,129.3,129.0,126.3,123.5, 120.3,117.7,114.3,110.7,83.2,63.5,61.9,61.8,55.3,14.1,13.9。
Claims (6)
1. a preparation method of a naphtho-dihydrooxazine compound is characterized in that: mixing a glycine derivative shown as a formula I, 2-naphthol, a photosensitizer, Lewis acid and a solvent under the conditions of air atmosphere and room temperature, reacting for 36 hours under the irradiation of visible light, and carrying out column chromatography to obtain a naphtho-dihydrooxazine compound, wherein the preparation process is shown as a formula I:
wherein R is1May be 4-phenyl, 4-benzyl, 4-methoxy, 4-ethoxy, 4-isopropyl, 4-n-butoxy, 4-phenoxy, 4-benzyloxy, 2, 5-dimethoxy, etc., R2Can be methyl, ethyl, isopropyl, tert-butyl, benzyl, etc., R3May be 6-bromo, 7-bromo, 6-methoxy, 7-methoxy, 6-carboxy, 6-methyl formate, 6-cyano, 7-ethoxy, 7-hydroxy, etc.
2. The method according to claim 1, wherein the photosensitizer is one of rhodamine B, rhodamine 6G, eosin Y, eosin B and rose bengal, and the amount of the photosensitizer is 1 to 5 mol% of the compound 2.
3. The process for preparing naphtho-dihydrooxazine compounds as claimed in claim 1, wherein the Lewis acid is one of copper sulfate, copper trifluoromethanesulfonate, copper bromide and cuprous chloride, and the amount of Lewis acid is 5-20 mol% of compound 2.
4. The method for preparing naphtho-dihydrooxazine compounds as claimed in claim 1, wherein the solvent is one of acetonitrile, toluene, ethyl acetate, and 1, 2-dichloroethane.
5. The method for preparing the naphtho-dihydrooxazine compound as claimed in claim 1, wherein the light source is one of a 5W blue LED lamp and a 26W energy-saving lamp.
6. The process for preparing naphtho-dihydrooxazines as claimed in claim 1, wherein the amount of compound 1 is 2.5 times equivalent to that of compound 2.
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| CN103664815A (en) * | 2014-01-07 | 2014-03-26 | 西北师范大学 | Preparation method of dihydrooxazinyl naphthalene compound |
| JP2015048429A (en) * | 2013-09-03 | 2015-03-16 | 四国化成工業株式会社 | Benzoxazine resin composition |
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| JP2015048429A (en) * | 2013-09-03 | 2015-03-16 | 四国化成工業株式会社 | Benzoxazine resin composition |
| CN103664815A (en) * | 2014-01-07 | 2014-03-26 | 西北师范大学 | Preparation method of dihydrooxazinyl naphthalene compound |
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| BIJOY P. MATHEW ET AL.: "One-Pot Three-Component Synthesis of Dihydrobenzo- and Naphtho[e]-1,3-oxazines in Water", 《JOURNAL OF HETEROCYCLIC CHEMISTRY》 * |
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