CN115286609A - Preparation method of 2-trifluoromethyl substituted dihydrobenzo chromene - Google Patents
Preparation method of 2-trifluoromethyl substituted dihydrobenzo chromene Download PDFInfo
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- CN115286609A CN115286609A CN202210949289.6A CN202210949289A CN115286609A CN 115286609 A CN115286609 A CN 115286609A CN 202210949289 A CN202210949289 A CN 202210949289A CN 115286609 A CN115286609 A CN 115286609A
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- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title abstract description 8
- -1 1-naphthol compound Chemical class 0.000 claims abstract description 40
- 238000006243 chemical reaction Methods 0.000 claims abstract description 28
- KJCVRFUGPWSIIH-UHFFFAOYSA-N alpha-naphthol Natural products C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 claims abstract description 15
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 12
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 12
- 239000011593 sulfur Substances 0.000 claims abstract description 12
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 8
- 239000000654 additive Substances 0.000 claims abstract description 7
- 230000000996 additive effect Effects 0.000 claims abstract description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- WFMNHCSATCWAAQ-UHFFFAOYSA-M potassium;2,2-dimethylpropanoate Chemical group [K+].CC(C)(C)C([O-])=O WFMNHCSATCWAAQ-UHFFFAOYSA-M 0.000 claims description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical group ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- LAXRNWSASWOFOT-UHFFFAOYSA-J (cymene)ruthenium dichloride dimer Chemical group [Cl-].[Cl-].[Cl-].[Cl-].[Ru+2].[Ru+2].CC(C)C1=CC=C(C)C=C1.CC(C)C1=CC=C(C)C=C1 LAXRNWSASWOFOT-UHFFFAOYSA-J 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 8
- 239000000758 substrate Substances 0.000 abstract description 6
- VCDAWCBLCCVSKE-UHFFFAOYSA-N 2h-benzo[h]chromene Chemical class C1=CC2=CC=CC=C2C2=C1C=CCO2 VCDAWCBLCCVSKE-UHFFFAOYSA-N 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 35
- UTFRXHNWUFPRPQ-UHFFFAOYSA-N 2,3-dichloro-1-methyl-4-propan-2-ylbenzene;ruthenium(2+) Chemical class [Ru+2].CC(C)C1=CC=C(C)C(Cl)=C1Cl UTFRXHNWUFPRPQ-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 150000004982 aromatic amines Chemical class 0.000 description 2
- 125000003963 dichloro group Chemical group Cl* 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- YAYGSLOSTXKUBW-UHFFFAOYSA-N ruthenium(2+) Chemical class [Ru+2] YAYGSLOSTXKUBW-UHFFFAOYSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- JFGQHAHJWJBOPD-UHFFFAOYSA-N 3-hydroxy-n-phenylnaphthalene-2-carboxamide Chemical compound OC1=CC2=CC=CC=C2C=C1C(=O)NC1=CC=CC=C1 JFGQHAHJWJBOPD-UHFFFAOYSA-N 0.000 description 1
- 241000227654 Reynoutria Species 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- OTUPBCGZQLZEQS-UHFFFAOYSA-N Salvonitin Natural products CCOc1c2OC(C=C(C)C)C(O)c3c(C)ccc(cc1C(C)C)c23 OTUPBCGZQLZEQS-UHFFFAOYSA-N 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 150000008371 chromenes Chemical class 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000011877 intramolecular nucleophilic addition Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical class C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- LCXUCRYVFHVKRP-UHFFFAOYSA-N trimethyl-$l^{3}-iodane Chemical class CI(C)C LCXUCRYVFHVKRP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/92—Naphthopyrans; Hydrogenated naphthopyrans
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 2-trifluoromethyl substituted dihydrobenzo chromene, which comprises the following steps: adding a catalyst, an additive, a 1-naphthol compound and trifluoroacetimide sulfur ylide into an organic solvent, reacting for 12-20 hours at the temperature of 80-120 ℃, and after the reaction is completed, carrying out post-treatment to obtain the 2-trifluoromethyl-substituted dihydrobenzo chromene. The preparation method is simple to operate, the initial raw materials are cheap and easy to obtain, the reaction efficiency is very high, gram-level reaction can be expanded, diversified dihydro benzo chromene compounds containing trifluoromethyl can be synthesized through substrate design, and the practicability of the method is widened while the operation is convenient.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of 2-trifluoromethyl substituted dihydrobenzo chromene.
Background
Dihydrobenzo chromene compounds are important polycyclic fused heterocyclic molecules widely found in natural products, bioactive molecules, drugs and luminescent materials (phytochem.lett.2019, 29,129-133 j.mater.chem.2007,17, 1885-1893. For example, salvonitin and Bispioterone are pharmaceutically active molecules isolated from the traditional Chinese medicine Reynoutria sanguinea (Planta Med.2013,29,150-156, bioorg.chem.2018,81, 454-460), propranolol analogs have β -blocking activity (chem.pharm.Bull.1990, 38, 3257-3260). At the same time, the presence of trifluoromethyl can significantly improve the physicochemical and pharmacodynamic properties of the heterocycle due to the unique nature of the fluorine atom (j.med. Chem.2015,58, 8315-8359).
At present, in literature reports, the method for synthesizing the dihydrobenzo chromene compound mainly takes naphthol as a raw material, and the naphthol is subjected to transition metal catalyzed oriented hydrocarbon activation reaction and is subjected to tandem cyclization reaction with different reaction substrates, such as functionalized alkyne, diazo compound and the like. The thioylide is an important carbene precursor and can be used as a good reaction substrate to participate in the tandem cyclization reaction. The trifluoroacetimide sulfur ylide is used as an ideal trifluoromethyl synthon and has a large application potential. Based on the method, a method for efficiently synthesizing 2-trifluoromethyl substituted dihydrobenzo chromene by using cheap and easily-obtained 1-naphthol compound and trifluoroacetimide sulfur ylide as starting materials and adopting a hydrocarbon activation-tandem cyclization reaction catalyzed by dichloro (p-methyl isopropylbenzene) ruthenium (II) dimer is developed.
Disclosure of Invention
The invention provides a preparation method of 2-trifluoromethyl substituted dihydrobenzo chromene, which has the advantages of simple steps, cheap and easily obtained reaction raw materials, extremely high reaction efficiency (the yield of a plurality of products is more than 95%), good reaction applicability and high functional group tolerance, can be efficiently expanded to gram-level reaction, and provides possibility for industrial large-scale production and application.
A method for preparing 2-trifluoromethyl substituted dihydrobenzo chromene comprises the following steps: adding a catalyst, an additive, a 1-naphthol compound and trifluoroacetimide sulfur ylide into an organic solvent, reacting for 12-20 hours at 80-120 ℃, and after the reaction is completed, carrying out post-treatment to obtain the 2-trifluoromethyl-substituted dihydrobenzo chromene;
the structure of the 1-naphthol compound is shown as the formula (II):
the structure of the trifluoroacetimide sulfur ylide is shown as the formula (III):
the structure of the 2-trifluoromethyl substituted dihydrobenzo chromene is shown as the formula (I):
in formulae (I) to (III), R 1 Selected from H, C 1 ～C 5 Alkyl radical, C 1 ～C 5 Alkoxycarbonyl, hydroxy or halogen;
R 2 selected from substituted or unsubstituted aryl, C 1 ～C 5 An alkyl group;
the substituent on the aryl is selected from C 1 ～C 5 Alkyl radical, C 1 ～C 5 Alkoxy, halogen, nitro or trifluoromethyl.
The molar ratio of the catalyst to the additive is 0.025.
The substitution position on the aryl group may be ortho, para or meta.
The reaction formula is as follows:
during the reaction, hydroxyl group-oriented carbon-hydrogen activation catalyzed by ruthenium and sulfur ylide reaction of trifluoroacetimide are probably carried out to form carbon-carbon bonds, then intramolecular nucleophilic addition reaction is carried out, and the hydroxyl group attacks carbon-nitrogen double bonds to obtain the final 2-trifluoromethyl-substituted dihydrobenzo chromene.
In the present invention, the optional post-processing procedure includes: filtering, mixing the sample with silica gel, and finally performing column chromatography purification to obtain the corresponding 2-trifluoromethyl-substituted dihydrobenzo chromene, wherein the column chromatography purification is a technical means commonly used in the field.
Preferably, R 1 Selected from H, methyl, methoxycarbonyl, hydroxyl or Br; r 2 Is selected from substituted or unsubstituted phenyl or naphthyl, and the substituent on the phenyl is selected from methyl, tertiary butyl, chlorine, bromine, nitro, F, nitro or trifluoromethyl, in this case, the trifluoroacetimide thioylide and 1-naphthol compound are easily obtained, and the yield of the reaction is high.
The aldehydes and glycines used to prepare the trifluoroacetimide thioylide are relatively inexpensive and widely available in nature, and the amount of trifluoroacetimide thioylide used is in excess relative to the 1-naphthol compound, and preferably, the molar amount of the 1-naphthol compound: trifluoroacetimide sulfur ylide: dichloro (p-methylisopropylbenzene) ruthenium (II) dimer: potassium pivalate = 1:1-2; as a further preference, the 1-naphthol compound: trifluoroacetimide sulfur ylide: dichloro (p-methylisopropylbenzene) ruthenium (II) dimer: potassium pivalate = 1.5.
Preferably, the reaction time is 12 to 20 hours, and if the reaction time is too long, the reaction cost increases, but it is difficult to ensure the completion of the reaction.
In the present invention, the organic solvent capable of sufficiently dissolving the raw material can cause the reaction, but the difference in reaction efficiency is large, and the aprotic solvent is preferably an aprotic solvent which can effectively promote the reaction; preferably, the organic solvent is tetrahydrofuran, acetonitrile or 1,2-dichloroethane; as a further preference, the organic solvent is 1,2-dichloroethane, in which case the various feedstocks can be converted into products with relatively high conversions.
The amount of the organic solvent is enough to dissolve the raw material well, and the amount of the organic solvent used for 1mmol of the 1-naphthol compound is about 5-10 mL.
Preferably, the catalyst is dichloro (p-cymene) ruthenium (II) dimer, which is relatively inexpensive among many transition metal catalysts, and the reaction efficiency is higher when dichloro (p-cymene) ruthenium (II) dimer is used as the catalyst.
Preferably, the additive is potassium pivalate.
As a further preference, the 2-trifluoromethyl substituted dihydrobenzo chromene is one of the compounds represented by the formulae (I-1) to (I-5):
in the above preparation method, the aromatic amine, the 1-naphthol compound, the dichloro (p-methylisoprophenyl) ruthenium (II) dimer and the potassium pivalate are generally commercially available products and can be conveniently obtained from the market, and the trifluoroacetimide sulfur ylide can be quickly synthesized from the corresponding aromatic amine, triphenylphosphine, carbon tetrachloride, trifluoroacetic acid and trimethyliodonium salt.
Compared with the prior art, the invention has the beneficial effects that: the preparation method is easy to operate, and the post-treatment is simple and convenient; the reaction starting raw materials are cheap and easy to obtain, the designability of the substrate is strong, the tolerance range of the substrate functional group is wide, the reaction efficiency is very high, 2-trifluoromethyl substituted dihydrobenzo chromene with different functional groups can be designed and synthesized according to actual needs, and the diversity and the practicability of the substrate structure are strong.
Detailed Description
The invention is further described with reference to specific examples.
Adding dichloro (p-methylisoprophenyl) ruthenium (II) dimer, potassium pivalate, 1-naphthol compound (II), trifluoroacetimide thioylide (III) and 2mL of organic solvent into a 35mL Schlenk tube according to the raw material ratio in a table 1, uniformly mixing and stirring, reacting for 12-20 hours according to the reaction conditions in a table 2, filtering, stirring with silica gel, and carrying out column chromatography purification to obtain the corresponding 2-trifluoromethyl substituted dihydrobenzo chromene (I), wherein the reaction process is shown as the following formula:
TABLE 1 raw material addition amounts for examples 1 to 15
TABLE 2
In tables 1 and 2, T is the reaction temperature, T is the reaction time, ph is phenyl, me is methyl, OMe is methoxy, NO 2 Is nitro, CF 3 Is trifluoromethyl and DCE is 1,2-dichloroethane.
Structure confirmation data of the compounds prepared in examples 1 to 5:
nuclear magnetic resonance of 2-trifluoromethyl-substituted dihydrobenzo chromene (I-1) prepared in example 1 (I-1) 1 H NMR、 13 C NMR and 19 f NMR) the data were:
1 H NMR(400M Hz,CDCl 3 )δ7.75(d,J＝8.3Hz,1H),7.51(d,J＝8.2Hz,1H),7.48–7.38(m,2H),7.23(d,J＝6.9Hz,1H),7.12(d,J＝7.5Hz,1H),6.93(d,J＝8.2Hz,2H),6.83(d,J＝8.2Hz,2H),3.80–3.70(br,1H),3.69(d,J＝16.4Hz,1H),3.35(d,J＝16.4Hz,1H),2.22(s,3H).
13 C NMR(101M Hz,CDCl 3 )δ148.7,139.4,133.7,131.6,129.3,127.2,126.8,126.3,125.5,124.2,124.0(C-F,q, 1 J (C-F) ＝288.2Hz),121.6,120.7,120.6,112.0,86.7(C-F,q, 2 J (C-F) ＝31.4Hz),33.6,20.7.
19 F NMR(377M Hz,CDCl 3 )δ-79.5.
M.p.99.7-102.4℃
HRMS(ESI):[M+H] + calcd.for C 20 H 17 F 3 NO + 344.1257,found 344.1255.
nuclear magnetic resonance of 2-trifluoromethyl-substituted dihydrobenzo chromene compound (I-2) prepared in example 2 ( 1 H NMR、 13 C NMR and 19 f NMR) the data were:
1 H NMR(400M Hz,CDCl 3 )δ7.71(d,J＝8.4Hz,1H),7.49–7.44(m,1H),7.42–7.33(m,2H),7.23–7.17(m,1H),7.18–7.10(m,2H),7.08–7.01(m,1H),6.81–6.69(m,2H),3.94(s,1H),3.81–3.51(m,1H),3.25(d,J＝16.4Hz,1H).
13 C NMR(101M Hz,CDCl 3 )δ148.0,141.4,133.7,131.6,127.3,127.0,126.4,124.8,124.4,123.9(C-F,q, 1 J (C-F) ＝287.9Hz),121.9,120.6,120.6,113.8,112.1,86.2(C-F,q, 2 J (C-F) ＝32.2Hz),33.4.
19 F NMR(377M Hz,CDCl 3 )δ-79.5.
M.p.112.8-114.5℃
HRMS(ESI):[M+H] + calcd.for C 19 H 14 BrF 3 NO 2 + 408.0205,found 408.0206.
nuclear magnetic resonance of 2-trifluoromethyl-substituted dihydrobenzo chromene compound (I-3) prepared in example 3 ( 1 H NMR、 13 C NMR and 19 f NMR) the data were:
1 H NMR(400M Hz,CDCl 3 )δ7.84(d,J＝7.9Hz,1H),7.77(d,J＝7.4Hz,1H),7.71(d,J＝8.4Hz,1H),7.53(d,J＝7.9Hz,1H),7.50(t,J＝7.8Hz,3H),7.48–7.34(m,3H),7.32(t,J＝8.2Hz,1H),7.27–7.18(m,1H),7.16(d,J＝6.9Hz,1H),4.49(s,1H),3.77(d,J＝16.5Hz,1H),3.61(d,J＝16.5Hz,1H).
13 C NMR(101M Hz,CDCl 3 )δ149.3,136.9,134.2,133.7,128.5,128.5,127.2,126.7,126.3,125.7,125.7,125.5,124.1(C-F,q, 1 J (C-F) ＝287.6Hz),124.0,123.8,121.5,121.3,120.5,119.2,111.6,87.3(C-F,q, 2 J (C-F) ＝31.3Hz),32.9.
19 F NMR(377M Hz,CDCl 3 )δ-80.1.
M.p.138.5-140.2℃
HRMS(ESI):[M+H] + calcd.for C 23 H 17 F 3 NO + 380.1257,found 380.1259.
nuclear magnetic resonance of 2-trifluoromethyl-substituted dihydrobenzo chromene compound (I-4) prepared in example 4 (I-4) 1 H NMR、 13 C NMR and 19 f NMR) the data were:
1 H NMR(400M Hz,CDCl 3 )δ7.77–7.64(m,1H),7.44(d,J＝8.3Hz,1H),7.43–7.35(m,1H),7.32(d,J＝8.3Hz,1H),7.23(d,J＝6.9Hz,1H),6.93(d,J＝8.2Hz,2H),6.78(d,J＝8.4Hz,2H),3.85–3.50(br,1H),3.79–3.61(m,1H),3.36(d,J＝16.2Hz,1H),2.46(s,3H),2.24(s,3H).
13 C NMR(101M Hz,CDCl 3 )δ145.4,139.3,132.2,131.7,130.4,129.1,126.8,125.2,124.8,124.2,124.1(C-F,q, 1 J (C-F) ＝287.5Hz),121.0,120.9,120.5,86.4(C-F,q, 2 J (C-F) ＝31.4Hz),33.7,20.7,15.6.
19 F NMR(377M Hz,CDCl 3 )δ-79.4.
HRMS(ESI):[M+H] + calcd.for C 21 H 19 F 3 NO + 358.1413,found 358.1414.
nuclear magnetic resonance of 2-trifluoromethyl-substituted dihydrobenzo chromene compound (I-5) prepared in example 5 (I-5) 1 H NMR、 13 C NMR and 19 f NMR) the data were:
1 H NMR(400M Hz,CDCl 3 )δ8.58(d,J＝8.7Hz,1H),8.14(d,J＝7.4Hz,1H),7.56(t,J＝8.2Hz,1H),7.27–7.05(m,2H),6.92(d,J＝8.0Hz,2H),6.80(d,J＝8.5Hz,2H),3.99(s,3H),3.98(s,1H),3.69(d,J＝16.6Hz,1H),3.39(d,J＝16.7Hz,1H),2.21(s,3H).
13 C NMR(101M Hz,CDCl 3 )δ167.7,148.8,139.1,131.9,131.6,131.3,130.6,129.3,129.1,126.1,123.9(C-F,q, 1 J (C-F) ＝288.3Hz),123.1,121.2,120.8,120.1,112.7,86.5(C-F,q, 2 J (C-F) ＝31.5Hz),77.5,52.3,33.8,20.7.
19 F NMR(377M Hz,CDCl 3 )δ-79.5.
M.p.141.8-143.3℃
HRMS(ESI):[M+H] + calcd.for C 22 H 19 F 3 NO 3 + 402.1312,found 402.1313。
Claims (7)
1. a method for preparing 2-trifluoromethyl substituted dihydrobenzo chromene is characterized by comprising the following steps: adding a catalyst, an additive, a 1-naphthol compound and trifluoroacetimide sulfur ylide into an organic solvent, reacting for 12-20 hours at 80-120 ℃, and after the reaction is completed, carrying out post-treatment to obtain the 2-trifluoromethyl-substituted dihydrobenzo chromene compound;
the structure of the 1-naphthol compound is shown as the formula (II):
the structure of the trifluoroacetimide sulfur ylide is shown as a formula (III):
the structure of the 2-trifluoromethyl substituted dihydrobenzo chromene is shown as the formula (I):
in formulae (I) to (III), R 1 Selected from H, C 1 ～C 5 Alkyl radical, C 1 ～C 5 Alkoxycarbonyl, hydroxy or halogen;
R 2 selected from substituted or unsubstituted aryl or C 1 ～C 5 An alkyl group;
the substituent on the aryl is selected from C 1 ～C 5 Alkyl radical, C 1 ～C 5 Alkoxy, halogen, nitro or trifluoromethyl.
2. The method of claim 1, wherein R is selected from the group consisting of 1 Selected from H, methyl, methoxycarbonyl, hydroxyl or Br;
R 2 selected from substituted or unsubstituted phenyl or naphthyl;
the substituent on the phenyl is selected from methyl, methoxy, tertiary butyl, chlorine, bromine, F, nitro or trifluoromethyl.
3. The method for producing 2-trifluoromethyl-substituted dihydrobenzo chromene according to claim 1, characterized in that, in terms of molar amount, the molar ratio of the 1-naphthol compound: trifluoroacetimide sulfur ylide: catalyst: additive = 1:1-2.
4. The method of claim 1, wherein the organic solvent is 1,2-dichloroethane.
5. The method of claim 1, wherein the catalyst is dichloro (p-cymene) ruthenium (II) dimer.
6. The method for preparing a 2-trifluoromethyl-substituted imidazole compound according to claim 1, wherein the additive is potassium pivalate.
7. The method of claim 1, wherein the 2-trifluoromethyl-substituted dihydrochromene is one of the compounds represented by the following formulae (I-1) to (I-5):
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| CN110256383A (en) * | 2019-06-25 | 2019-09-20 | 浙江大学城市学院 | Dibenzofurans acrylic ester compound and preparation method thereof |
| CN110526855A (en) * | 2019-09-29 | 2019-12-03 | 郑州大学 | A kind of preparation method for the indole derivatives that 3- nitroso replaces |
| CN111423381A (en) * | 2020-01-17 | 2020-07-17 | 浙江理工大学 | Preparation method of 2-trifluoromethyl substituted imidazole compound |
| CN112812084A (en) * | 2020-12-30 | 2021-05-18 | 温州大学新材料与产业技术研究院 | Synthetic method of benzofuran compound |
| CN113045530A (en) * | 2021-03-23 | 2021-06-29 | 成都大学 | Method for preparing naphthopyran compounds by ruthenium catalysis |
| CN113735778A (en) * | 2020-12-23 | 2021-12-03 | 浙江理工大学 | Preparation method of 5-trifluoromethyl substituted imidazole compound |
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| CN110256383A (en) * | 2019-06-25 | 2019-09-20 | 浙江大学城市学院 | Dibenzofurans acrylic ester compound and preparation method thereof |
| CN110526855A (en) * | 2019-09-29 | 2019-12-03 | 郑州大学 | A kind of preparation method for the indole derivatives that 3- nitroso replaces |
| CN111423381A (en) * | 2020-01-17 | 2020-07-17 | 浙江理工大学 | Preparation method of 2-trifluoromethyl substituted imidazole compound |
| CN113735778A (en) * | 2020-12-23 | 2021-12-03 | 浙江理工大学 | Preparation method of 5-trifluoromethyl substituted imidazole compound |
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| CN113045530A (en) * | 2021-03-23 | 2021-06-29 | 成都大学 | Method for preparing naphthopyran compounds by ruthenium catalysis |
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