CN111116662A - Preparation method of fluoro cyclic phosphonamide derivative - Google Patents
Preparation method of fluoro cyclic phosphonamide derivative Download PDFInfo
- Publication number
- CN111116662A CN111116662A CN201911119386.7A CN201911119386A CN111116662A CN 111116662 A CN111116662 A CN 111116662A CN 201911119386 A CN201911119386 A CN 201911119386A CN 111116662 A CN111116662 A CN 111116662A
- Authority
- CN
- China
- Prior art keywords
- compound
- cdcl
- nmr
- preparation
- mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 65
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims abstract description 48
- 238000006243 chemical reaction Methods 0.000 claims abstract description 47
- 238000000034 method Methods 0.000 claims abstract description 26
- 239000000203 mixture Substances 0.000 claims abstract description 25
- 238000004809 thin layer chromatography Methods 0.000 claims abstract description 25
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000010898 silica gel chromatography Methods 0.000 claims abstract description 24
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims abstract description 24
- 238000002156 mixing Methods 0.000 claims abstract description 4
- 238000001816 cooling Methods 0.000 claims abstract description 3
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims abstract 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 63
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 42
- -1 1,2,3,4, 5-pentafluorophenyl Chemical group 0.000 claims description 33
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 23
- 239000003208 petroleum Substances 0.000 claims description 21
- 239000007787 solid Substances 0.000 claims description 20
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- WIKQEUJFZPCFNJ-UHFFFAOYSA-N carbonic acid;silver Chemical compound [Ag].[Ag].OC(O)=O WIKQEUJFZPCFNJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 claims description 4
- KQTXIZHBFFWWFW-UHFFFAOYSA-L silver(I) carbonate Inorganic materials [Ag]OC(=O)O[Ag] KQTXIZHBFFWWFW-UHFFFAOYSA-L 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 230000035484 reaction time Effects 0.000 abstract description 11
- 238000003786 synthesis reaction Methods 0.000 abstract description 7
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 114
- 238000001228 spectrum Methods 0.000 description 38
- 238000002844 melting Methods 0.000 description 37
- 230000008018 melting Effects 0.000 description 37
- 238000012512 characterization method Methods 0.000 description 32
- 229910052739 hydrogen Inorganic materials 0.000 description 29
- 239000001257 hydrogen Substances 0.000 description 29
- 239000000047 product Substances 0.000 description 23
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 19
- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
- 238000004679 31P NMR spectroscopy Methods 0.000 description 19
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 19
- 229910052799 carbon Inorganic materials 0.000 description 19
- 239000012043 crude product Substances 0.000 description 19
- 238000000746 purification Methods 0.000 description 19
- 238000001819 mass spectrum Methods 0.000 description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 12
- 150000002431 hydrogen Chemical class 0.000 description 10
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 5
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000004896 high resolution mass spectrometry Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000001308 synthesis method Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000575 pesticide Substances 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- RNFJDJUURJAICM-UHFFFAOYSA-N 2,2,4,4,6,6-hexaphenoxy-1,3,5-triaza-2$l^{5},4$l^{5},6$l^{5}-triphosphacyclohexa-1,3,5-triene Chemical compound N=1P(OC=2C=CC=CC=2)(OC=2C=CC=CC=2)=NP(OC=2C=CC=CC=2)(OC=2C=CC=CC=2)=NP=1(OC=1C=CC=CC=1)OC1=CC=CC=C1 RNFJDJUURJAICM-UHFFFAOYSA-N 0.000 description 2
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 239000003063 flame retardant Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000005541 phosphonamide group Chemical group 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- DQXKOHDUMJLXKH-PHEQNACWSA-N (e)-n-[2-[2-[[(e)-oct-2-enoyl]amino]ethyldisulfanyl]ethyl]oct-2-enamide Chemical compound CCCCC\C=C\C(=O)NCCSSCCNC(=O)\C=C\CCCCC DQXKOHDUMJLXKH-PHEQNACWSA-N 0.000 description 1
- 238000010499 C–H functionalization reaction Methods 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- ITVPBBDAZKBMRP-UHFFFAOYSA-N chloro-dioxido-oxo-$l^{5}-phosphane;hydron Chemical compound OP(O)(Cl)=O ITVPBBDAZKBMRP-UHFFFAOYSA-N 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229940042400 direct acting antivirals phosphonic acid derivative Drugs 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 150000003007 phosphonic acid derivatives Chemical class 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
- C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
- C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
- C07F9/65846—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring the phosphorus atom being part of a six-membered ring which may be condensed with another ring system
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of organic synthesis, and discloses a preparation method of a fluoro cyclic phosphonamide derivative. The preparation method comprises the steps of mixing a compound I, a compound II and Ag in a microwave reaction tube2CO3、NaHCO3、[RhCp*Cl2]2Mixing the mixture and 1, 2-dichloroethane, placing the mixture in a microwave reactor, reacting for 5-60 min at 90-140 ℃, and detecting by Thin Layer Chromatography (TLC) until the reaction is complete; and (2) cooling the product obtained in the step (1) to room temperature, pressurizing and concentrating, and separating and purifying by silica gel column chromatography to obtain a pure product. The method can be used for synthesizing the fluoro cyclic phosphonamide derivative, and has the advantages of simple steps, short reaction time, high heat energy utilization rate and high yield.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of a fluoro cyclic phosphonamide derivative.
Background
The cyclic organic phosphine compound has wide application in the fields of synthetic chemistry, medicinal chemistry, pesticide chemistry, bioengineering, chemical materials and the like, and is closely related to the life activities of human beings. For example, in synthetic chemistry, cyclic organophosphinic compounds are important building blocks for the construction of organic intermediates, and are essential components for various metal catalysts as ligands. In pharmaceutical and agrochemical molecules, fragments containing cyclic phosphine structures are often the sites where compounds exhibit biological activity. Among chemical materials, they are core structures that many photoelectric materials and flame retardant materials exhibit phosphorescent and flame retardant properties. Therefore, it is of great significance to develop a simple and efficient synthetic method to construct various organic phosphine compounds with novel structures.
The synthesis method of the phosphonamide mainly comprises the following steps: 1. acylation of phosphonochloride and an amine. 2. Condensation reaction of phosphonic acid derivatives and amines. 3. Alkylation of primary phosphonamides, and the like. However, these synthetic methods are mainly used for preparing non-cyclic phosphoramides, but are not applicable to the synthesis of cyclic phosphoramides.
With the rapid development of modern transition metal catalyzed organic synthesis processes. Alkyne and alkene are taken as coupling reagents, and C-H activation/cyclization reaction catalyzed by transition metal such as ruthenium, rhodium and palladium can be directly used for constructing the cyclic phosphonamide derivative. The method is simpler and more effective in synthesis steps and atom economy than the traditional method.
However, the synthesis method of the cyclic phosphonamide derivative has the following disadvantages: 1. the preparation method adopts the traditional chemical synthesis method, adopts oil bath heating, and has extremely low heat energy utilization rate. 2. The oil bath is adopted for heating, the required reaction time is as short as more than ten hours, and is as long as 1-2 days, the reaction time is long, and the reaction efficiency is low. 3. The preparation method aiming at the fluoro cyclic phosphonamide derivative is few, and the yield of the product is extremely low.
Disclosure of Invention
The invention provides a preparation method of fluoro cyclic phosphonamide derivatives, which has the advantages of simple steps, short reaction time, high heat energy utilization rate and high yield.
In order to solve the technical problems, the preparation method of the fluoro cyclic phosphonamide derivative is characterized in that the synthetic route is as follows:
wherein, ArFn in the compound I can be 4-fluorophenyl, 3, 5-difluorophenyl, 1,2,3,4, 5-pentafluorophenyl; substituent R1Can be methyl, methoxy, tert-butyl, trifluoromethyl, fluorine, chlorine; substituent R2Can be 4-methylphenyl, 4-methoxyphenyl, 3, 4-dimethylphenyl, 4-trifluoromethylphenyl, 4-fluorophenyl, 4-chlorophenyl or n-propyl.
Further, the synthesis steps are as follows:
(1) in a microwave reaction tube, compound I, compound II and Ag2CO3、NaHCO3、 [RhCp*Cl2]2Mixing the mixture and 1, 2-dichloroethane, placing the mixture in a microwave reactor, reacting for 5-60 min at 90-140 ℃, and detecting by Thin Layer Chromatography (TLC) until the reaction is complete;
(2) and (2) cooling the product obtained in the step (1) to room temperature, concentrating under reduced pressure, and separating and purifying by silica gel column chromatography to obtain a pure product.
Further, the preparation method is carried out under the condition of microwave.
Preferably, the compound I, the compound II and Ag2CO3、NaHCO3、[RhCp*Cl2]2And the mixed molar ratio of the 1, 2-dichloroethane is 1: (1-3): (1-3): (1-3): (0.01-0.05): (5-10).
Preferably, the volume ratio of the petroleum ether to the ethyl acetate in the silica gel column chromatography is 8: 1-3: 1.
More preferably, said step (2) results in a pure product as a light yellow solid.
One or more technical solutions provided in the embodiments of the present application have at least the following technical effects or advantages:
(1) the preparation method can be used for synthesizing the fluorinated cyclic phosphoramide derivative, has simple steps, wide raw material sources, low preparation cost and mild reaction conditions, and has the maximum yield of the fluorinated cyclic phosphoramide derivative reaching 90 percent.
(2) The existing synthesis method adopts oil bath heating, and the reaction time is short, namely more than ten hours, and more than 1 to 2 days. The preparation method is carried out under the condition of microwave, the reaction time is more than 1 hour and less than 15 minutes, and the reaction time is greatly shortened, so that the heat energy utilization rate is effectively improved.
(3) The fluorine-containing cyclic phosphoramide derivative prepared by the preparation method has obvious activity in physiological and pharmacological aspects, and has important significance for developing fluorine-containing organic phosphine medical pesticides.
Detailed Description
In order to better understand the technical solutions, the technical solutions will be described in detail below with reference to specific embodiments, and it should be understood that the specific features in the examples and the embodiments of the present invention are detailed descriptions of the technical solutions of the present application, but not limitations of the technical solutions of the present application, and the technical features in the examples and the embodiments of the present application may be combined with each other without conflict.
Example 1
In this embodiment: ArFnIs 4-fluorophenyl, R1Is hydrogen, R2Is phenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-1(0.3mmol), compound II-1(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 90 ℃ for 5min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 8:1, to give the pure product as a pale yellow solid, yield: 71 percent.
And (3) performing characterization tests on the compound III-1, wherein the characterization tests comprise a melting point test, a nuclear magnetic hydrogen spectrum, a nuclear magnetic carbon spectrum and a high-resolution mass spectrum:
melting point: 77-78 deg.C
1H NMR(400MHz,CDCl3)δ7.70(dd,J＝12.7,7.4Hz,2H),7.56(dd,J＝14.2, 7.5Hz,1H),7.42(dd,J＝18.1,7.8Hz,2H),7.31(dd,J＝10.0,6.9Hz,3H),7.15 (dd,J＝14.9,10.0Hz,6H),7.04–6.91(m,4H),6.90–6.77(m,3H),6.56(t,J＝ 8.4Hz,2H)。
13C NMR(100MHz,CDCl3)δ161.67,159.21,140.96,138.76(d,J＝5Hz), 138.20,136.07(d,J＝4Hz),135.62,133.06(d,J＝10Hz),132.08,131.88(d,J＝ 2Hz),131.68(d,J＝7Hz),131.52(dd,J＝8,3Hz),130.99(d,J＝19Hz),130.78, 130.29,128.00,127.87,126.94,126.87,126.53,126.48,126.37(d,J＝5Hz), 126.20。
31P NMR(162MHz,CDCl3)δ16.22。
HRMS m/z:calcd for C32H24FNOP[M+H+]488.1574,found 488.1577。
Example 2
In this embodiment: ArFnIs 3, 5-difluorophenyl, R1Is hydrogen, R2Is phenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-2(0.3mmol), compound II-1(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 140 ℃ for 60min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 3:1, to give the pure product as a pale yellow solid, yield: 78 percent.
And (3) performing characterization tests on the compound III-2, wherein the characterization tests comprise a melting point test, a nuclear magnetic hydrogen spectrum, a nuclear magnetic carbon spectrum and a high-resolution mass spectrum:
melting point: 94-95 deg.C
1H NMR(400MHz,CDCl3)δ7.80–7.69(m,2H),7.54(ddd,J＝14.3,7.6,1.0 Hz,1H),7.49–7.42(m,2H),7.40–7.28(m,3H),7.25–7.12(m,6H),7.01(dd,J ＝7.9,1.4Hz,2H),6.95–6.83(m,3H),6.69–6.59(m,2H),6.25(tt,J＝8.8,2.2 Hz,1H)。
13C NMR(100MHz,CDCl3)δ163.16(d,J＝14Hz),160.69(d,J＝14Hz), 142.68,142.56,142.43,139.43,138.32(d,J＝5Hz),137.74(d,J＝1Hz),135.75 (d,J＝3Hz),133.03(d,J＝10Hz),132.26(d,J＝3Hz),131.94,131.43(d,J＝ 9.7Hz),130.76,130.64,129.58,128.15(d,J＝13Hz),127.95,127.18(d,J＝7 Hz),126.81(d,J＝7Hz),126.69(d,J＝3Hz),124.11,122.83,121.78(d,J＝7 Hz),112.65(d,J＝3Hz),112.38(d,J＝3Hz),101.82,101.57,101.32。
31P NMR(162MHz,CDCl3)δ16.40。
HRMS m/z:calcd for C32H23F2NOP[M+H+]506.1480,found 506.1478。
Example 3
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, R1Is hydrogen, R2Is phenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-3(0.3mmol), compound II-1(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 100 ℃ for 30min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 5:1, to give the pure product as a white solid, yield: 93 percent.
And (3) performing characterization tests on the compound III-3, wherein the characterization tests comprise a melting point test, a nuclear magnetic hydrogen spectrum, a nuclear magnetic carbon spectrum and a high-resolution mass spectrum:
melting point: 184-185 deg.C
1H NMR(400MHz,CDCl3)δ7.80(dd,J＝13.2,8.0Hz,2H),7.71(ddd,J ＝14.2,7.6,1.0Hz,1H),7.59–7.48(m,2H),7.48–7.42(m,2H),7.41-7.36 (m,1H),7.24-7.14(m,6H),7.07–7.00(m,2H),6.99–6.90(m,3H)。
13C NMR(100MHz,CDCl3)δ139.45,138.80(d,J＝5Hz),137.23,135.23 (d,J＝4Hz),132.84(d,J＝2Hz),132.33(d,J＝2Hz),132.18(d,J＝1Hz), 132.07(d,J＝1Hz),131.64,131.20,130.20(d,J＝11Hz),129.90,129.29, 128.39,128.25(d,J＝1Hz),128.03,127.55,127.24,127.10,126.95,126.85, 123.57,122.32,122.18(d,J＝7Hz)。
31P NMR(162MHz,CDCl3)δ18.02。
HRMS m/z:calcd for C32H20F5NOP[M+H+]560.1197,found 560.1199。
Example 4
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, R1Is 2-methyl, R2Is phenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-4(0.3mmol), compound II-1(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 110 ℃ for 30min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 3:1, to give the pure product as a pale yellow solid, yield: 62 percent.
And (3) performing characterization tests on the compound III-4, wherein the characterization tests comprise a melting point test, a nuclear magnetic hydrogen spectrum, a nuclear magnetic carbon spectrum and a high-resolution mass spectrum:
melting point: 96-97 deg.C
1H NMR(400MHz,CDCl3)δ8.25(ddd,J＝14.7,7.6,1.3Hz,1H),7.53– 7.46(m,1H),7.41(dd,J＝7.5,2.9Hz,1H),7.39–7.33(m,3H),7.33–7.30 (m,1H),7.26–7.22(m,3H),7.21-7.18(m,2H),7.16–7.03(m,4H),6.88 (dd,J＝8.1,4.5Hz,1H),2.29(s,3H),2.19(s,3H)。
13C NMR(101MHz,CDCl3)δ146.27(d,J＝11Hz),141.80(d,J＝10Hz), 140.55(d,J＝11Hz),139.47(d,J＝6Hz),136.66,134.79(d,J＝5Hz), 134.45(d,J＝12Hz),132.95(d,J＝2Hz),132.19(d,J＝2Hz),131.82, 131.48(d,J＝12Hz),130.74,130.22,130.09,129.33,128.99,128.79,128.32, 127.70,127.49,125.87,125.73,125.15(d,J＝9Hz),122.47,121.21,118.83 (d,J＝10Hz),21.32(d,J＝6Hz),20.63(d,J＝4Hz)。
31P NMR(162MHz,CDCl3)δ21.69。
HRMS m/z:calcd for C34H24F5NOP[M+H+]588.1510,found 588.1503。
Example 5
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, R1Is 3-methyl, R2Is phenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-5(0.3mmol), compound II-1(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 100 ℃ for 20min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 7:1, to give the pure product as a tan solid, yield: 73 percent.
And (3) performing characterization tests on the compound III-5, wherein the characterization tests comprise a melting point test, a nuclear magnetic hydrogen spectrum, a nuclear magnetic carbon spectrum and a high-resolution mass spectrum:
melting point: 79-80 deg.C
1H NMR(400MHz,CDCl3)δ7.68(d,J＝13.6Hz,1H),7.62–7.45(m,2H), 7.39–7.27(m,3H),7.25–7.12(m,5H),7.09(dd,J＝8.3,5.5Hz,1H),7.02(dd, J＝9.8,6.1Hz,2H),6.93(p,J＝3.5Hz,3H),2.37(d,J＝6.7Hz,3H),2.34(s, 3H)。
13C NMR(100MHz,CDCl3)δ138.55,138.24,138.10,137.47,137.33, 136.21(d,J＝6Hz),135.36(d,J＝4Hz),133.57(d,J＝3Hz),133.29(d,J＝2 Hz),132.41(dd,J＝11,2Hz),131.60,131.32,130.18,(d,J＝11Hz),130.02, 129.36,129.13(dd,J＝11,2Hz),128.28,128.14,128.10,127.97,127.50,126.97, 126.85,123.64,122.40,122.27(d,J＝7Hz),21.29,21.05。
31P NMR(162MHz,CDCl3)δ18.74。
HRMS m/z:calcd for C34H24F5NOP[M+H+]588.1510,found 588.1496。
Example 6
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, R1Is 4-methyl, R2Is phenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-6(0.3mmol), compound II-1(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 110 ℃ for 15min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 4:1, to give the pure product as a pale yellow solid, yield: 84 percent.
And (3) performing characterization tests on the compound III-6, wherein the characterization tests comprise a melting point test, a nuclear magnetic hydrogen spectrum, a nuclear magnetic carbon spectrum and a high-resolution mass spectrum:
melting point: 171 ℃ 172 ℃
1H NMR(400MHz,CDCl3)δ7.67(dd,J＝13.0,7.9Hz,2H),7.58(dd,J＝ 14.0,7.8Hz,1H),7.26–7.21(m,3H),7.21–7.12(m,5H),7.06–7.00(m,2H), 6.98(d,J＝4.9Hz,1H),6.96–6.89(m,3H),2.39(s,3H),2.31(s,3H)。
13C NMR(100MHz,CDCl3)δ143.40(d,J＝3Hz),142.70(d,J＝2Hz), 139.49,138.76(d,J＝6Hz),137.40,135.45(d,J＝3Hz),132.19(dd,J＝11,1 Hz),131.71,130.26,130.15,129.32,129.13,128.99,128.24,128.11,127.96, 127.48,127.23,127.14,126.85,122.10(d,J＝2Hz),121.04,119.76,22.00, 21.69。
31P NMR(162MHz,CDCl3)δ18.83。
HRMS m/z:calcd for C34H24F5NOP[M+H+]588.1510,found 588.1507。
Example 7
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, R1Is 4-methoxy, R2Is phenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-7(0.3mmol), compound II-1(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 130 ℃ for 60min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 4:1, to give the pure product as a white solid, yield: 77 percent.
And (3) performing characterization tests on the compound III-7, wherein the characterization tests comprise a melting point test, a nuclear magnetic hydrogen spectrum, a nuclear magnetic carbon spectrum and a high-resolution mass spectrum:
melting point: 85-86 deg.C
1H NMR(400MHz,CDCl3)δ7.71(dd,J＝12.2,8.6Hz,2H),7.62(dd,J＝ 13.8,8.5Hz,1H),7.25–7.10(m,5H),7.03-6.99(m,2H),6.97–6.86(m, 6H),6.66(dd,J＝4.4,2.4Hz,1H),3.85(s,3H),3.70(s,3H)。
13C NMR(100MHz,CDCl3)δ163.00(d,J＝3Hz),162.56(d,J＝3Hz), 140.95(d,J＝7Hz),140.13,137.35,135.47(d,J＝4Hz),134.19(dd,J＝13, 2Hz),132.21(d,J＝12Hz),131.65,131.56,129.24,128.15,128.08,128.01, 127.50,126.91,122.67,121.54(d,J＝6Hz),121.28,113.81(d,J＝14Hz), 113.20(d,J＝5Hz),112.98(d,J＝10Hz),55.33,55.15。
31P NMR(162MHz,CDCl3)δ18.75。
HRMS m/z:calcd for C34H24F5NO3P[M+H+]620.1408,found 620.1425。
Example 8
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, R1Is 4-tert-butyl, R2Is phenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-8(0.3mmol), compound II-1(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 95 ℃ for 40min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 5:1, to give the pure product as a pale yellow solid, yield: 88 percent.
And (3) performing characterization tests on the compound III-8, wherein the characterization tests comprise a melting point test, a nuclear magnetic hydrogen spectrum, a nuclear magnetic carbon spectrum and a high-resolution mass spectrum:
melting point: 158 ℃ to 159 DEG C
1H NMR(400MHz,CDCl3)δ7.71(dd,J＝12.8,8.2Hz,2H),7.65(dd,J ＝13.8,8.1Hz,1H),7.45(d,J＝3.2Hz,1H),7.44–7.37(m,2H),7.25–7.12 (m,6H),7.04(d,J＝2.9Hz,2H),6.98–6.89(m,3H),1.31(s,9H),1.19(s, 9H)。
13C NMR(100MHz,CDCl3)δ156.35(d,J＝3Hz),155.55(d,J＝3Hz), 139.32,138.59(d,J＝6Hz),137.53,135.60(d,J＝3Hz),132.04(dd,J＝12,2 Hz),131.71,130.05,129.93,129.40,128.19,128.08,127.89,127.50,126.86, 126.82,125.19(d,J＝4Hz),124.58(d,J＝4Hz),123.74(d,J＝10Hz),122.09(d, J＝7Hz),120.86,119.58,35.16,35.08,31.02,30.92。
31P NMR(162MHz,CDCl3)δ18.48。
HRMS m/z:calcd for C40H36F5NOP[M+H3O+]690.2555,found 690.2578。
Example 9
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, R1Is 4-trifluoromethyl, R2Is phenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-9(0.3mmol), compound II-1(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 90 ℃ for 60min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 6:1, to give the pure product as an off-white solid, yield: 87 percent.
And (3) performing characterization tests on the compound III-9, wherein the characterization tests comprise a melting point test, a nuclear magnetic hydrogen spectrum, a nuclear magnetic carbon spectrum and a high-resolution mass spectrum:
melting point: 208 ℃ to 209 DEG C
1H NMR(400MHz,CDCl3)δ7.88(dd,J＝12.9,8.1Hz,2H),7.77(dd,J＝ 13.8,8.0Hz,1H),7.69(dd,J＝8.2,2.7Hz,2H),7.57(d,J＝7.9Hz,1H),7.40(d, J＝4.4Hz,1H),7.24–7.02(m,5H),7.00–6.80(m,5H)。
13C NMR(100MHz,CDCl3)δ141.31,139.60(d,J＝6Hz),135.91,135.38, 134.92(dd,J＝19,3Hz),134.60(dd,J＝18,3Hz),134.45(d,J＝3Hz),134.09, 132.33(dd,J＝11,2Hz),131.37,131.10,130.99,129.02,128.80,128.48,127.81, 127.63,125.90,125.56(q,J＝4Hz),125.42(q,J＝4Hz),124.65(d,J＝3Hz), 123.91—123.58(m),121.93(d,J＝3Hz),121.53(d,J＝7Hz)。
31P NMR(162MHz,CDCl3)δ15.38。
HRMS m/z:calcd for C34H18F11NOP[M+H+]696.0945,found 696.0963。
Example 10
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, R1Is 4-fluoro, R2Is phenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-10(0.3mmol), compound II-1(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 3.0mL of 1, 2-dichloroethane), the mixture was placed in a microwave reactor at 110 ℃ for 15min, and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 3:1, to give the pure product as a white solid, yield: 82 percent.
And (3) performing characterization tests on the compound III-10, wherein the characterization tests comprise a melting point test, a nuclear magnetic hydrogen spectrum, a nuclear magnetic carbon spectrum and a high-resolution mass spectrum:
melting point: 201-
1H NMR(400MHz,CDCl3)δ7.86–7.75(m,2H),7.74-7.67(m,1H), 7.29–7.11(m,7H),7.11–7.06(m,1H),7.04–6.98(m,2H),6.98–6.91(m, 3H),6.89-6.85(m,1H)。
13C NMR(100MHz,CDCl3)δ166.72(dd,J＝24,4Hz),164.20(dd,J＝18, 4Hz),141.96(dd,J＝9,7Hz),140.98,136.58,134.85,134.73,134.63,132.99 (dd,J＝13,10Hz),131.47,129.06,128.54,128.30,127.69,127.32,121.03 (dd,J＝7,3Hz),119.29(d,J＝3Hz),118.99(d,J＝2Hz),115.93(dd,J＝21, 15Hz),115.04(dd,J＝22,5Hz),113.62(dd,J＝23,11Hz)。
31P NMR(162MHz,CDCl3)δ16.77。
HRMS m/z:calcd for C32H18F7NOP[M+H+]596.1009,found 596.1025。
Example 11
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, R1Is 4-chloro, R2Is phenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-11(0.3mmol), compound II-1(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 130 ℃ for 10min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 6:1, to give the pure product as an off-white solid, yield: 68 percent.
And (3) performing characterization tests on the compound III-11, wherein the characterization tests comprise a melting point test, a nuclear magnetic hydrogen spectrum, a nuclear magnetic carbon spectrum and a high-resolution mass spectrum:
melting point: 87-88 deg.C
1H NMR(400MHz,CDCl3)δ7.72(dd,J＝12.8,8.2Hz,2H),7.63(dd,J＝ 13.9,8.2Hz,1H),7.46(dd,J＝8.4,2.8Hz,2H),7.37(dt,J＝8.2,2.1Hz,1H), 7.26–7.21(m,2H),7.21–7.15(m,2H),7.15–7.09(m,2H),7.05–6.90(m, 5H)。
13C NMR(100MHz,CDCl3)δ141.04,140.57(d,J＝7Hz),139.80(d,J＝5 Hz),139.38(d,J＝3Hz),136.33,134.73(d,J＝3Hz),133.37(dd,J＝12,2Hz), 131.68(d,J＝12Hz),131.47,129.69,129.06,129.00,128.85,128.59,128.33, 127.70,127.67,127.53,127.38,126.79(d,J＝10Hz),121.32,121.16,121.09, 120.04。
31P NMR(162MHz,CDCl3)δ16.78。
HRMS m/z:calcd for C32H18Cl2F5NOP[M+H+]628.0418,found 628.0406。
Example 12
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, R1Is hydrogen, R2Is 4-methylphenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-1(0.3mmol), compound II-2(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 100 ℃ for 50min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 7:1, to give the pure product as a tan solid, yield: 92 percent.
Compound III-12 was subjected to characterization tests including melting point test, nuclear magnetic hydrogen spectrum, nuclear magnetic carbon spectrum and high resolution mass spectrometry:
melting point: 191 plus 192 DEG C
1H NMR(400MHz,CDCl3)δ7.79(dd,J＝13.2,7.9Hz,2H),7.72-7.67(m, 1H),7.57–7.40(m,4H),7.39–7.33(m,1H),7.20(dd,J＝8.0,5.2Hz,1H),7.08 –7.00(m,4H),6.92(d,J＝7.9Hz,2H),6.74(d,J＝7.9Hz,2H),2.27(s,3H), 2.09(s,3H)。
13C NMR(100MHz,CDCl3)δ139.36,139.19(d,J＝6Hz),137.91,136.40, 134.29,132.76(d,J＝3Hz),132.42(d,J＝4Hz),132.23(d,J＝3Hz),132.06(q, J＝1Hz),131.42,131.35,130.01(d,J＝11Hz),129.17,128.74,128.35,128.27, 128.22,127.08,126.96(d,J＝4Hz),126.88,123.61,122.31(d,J＝8Hz),21.15, 21.13。
31P NMR(162MHz,CDCl3)δ18.25。
HRMS m/z:calcd for C34H24F5NOP[M+H+]588.1510,found 588.1516。
Example 13
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, R1Is hydrogen, R2Is 4-methoxyphenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-1(0.3mmol), compound II-3(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 120 ℃ for 50min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 8:1, to give the pure product as a tan solid, yield: 78 percent.
Compound III-13 was subjected to characterization tests including melting point test, nuclear magnetic hydrogen spectrum, nuclear magnetic carbon spectrum and high resolution mass spectrum:
melting point: 93-94 deg.C
1H NMR(400MHz,CDCl3)δ7.78(dd,J＝13.2,7.7Hz,2H),7.73–7.64(m, 1H),7.58–7.47(m,2H),7.43(td,J＝7.5,3.5Hz,2H),7.36(td,J＝7.4,2.8Hz, 1H),7.23(dd,J＝8.0,5.2Hz,1H),7.07(d,J＝8.6Hz,2H),6.95(d,J＝8.6Hz, 2H),6.77(d,J＝8.7Hz,2H),6.47(d,J＝8.8Hz,2H),3.76(s,3H),3.62(s,3H)。
13C NMR(100MHz,CDCl3)δ158.92,158.25,139.33(t,J＝5Hz),132.77(d, J＝2Hz),132.62,132.12(td,J＝12,3Hz),130.65,130.08,129.96,129.63, 128.28(d,J＝13Hz),127.82(d,J＝3Hz),127.05,126.91,126.81,123.58, 122.32,121.94(d,J＝2Hz),116.20,114.88,113.49,112.96,55.09,54.90。
31P NMR(162MHz,CDCl3)δ18.28。
HRMS m/z:calcd for C34H24F5NO3P[M+H+]620.1408,found 620.1416。
Example 14
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, R1Is hydrogen, R2Is 3, 4-dimethylphenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-1(0.3mmol), compound II-4(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 90 ℃ for 45min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 3:1, to give the pure product as a pale yellow solid, yield: 65 percent.
Compound III-14 was subjected to characterization tests including melting point test, nuclear magnetic hydrogen spectrum, nuclear magnetic carbon spectrum and high resolution mass spectrometry:
melting point: 74-75 deg.C
1H NMR(400MHz,CDCl3)δ7.79(dd,J＝13.1,7.6Hz,2H),7.67(dd,J＝ 14.3,7.1Hz,1H),7.55–7.41(m,4H),7.35(td,J＝7.4,2.6Hz,1H),7.23(dt, J＝7.9,7.1Hz,2H),6.96(d,J＝8.0Hz,2H),6.88–6.83(m,2H),6.76(d,J＝ 7.7Hz,1H),6.67(d,J＝7.8Hz,1H),2.18(s,3H),2.17(s,3H),2.00(s,3H), 1.96(s,3H)。
13C NMR(100MHz,CDCl3)δ139.40(d,J＝5Hz),139.21,136.46,135.88, 135.51,134.92,134.72,132.79,132.73(d,J＝3Hz),132.15(d,J＝2Hz),132.05, 131.31,130.43,130.01,129.86(d,J＝3Hz),129.17,128.95,128.68,128.25(d,J ＝4Hz),127.04(t,J＝8Hz),126.82,123.67,122.48(t,J＝7Hz),19.66,19.43, 19.26。
31P NMR(162MHz,CDCl3)δ18.19。
HRMS m/z:calcd for C36H28F5NOP[M+H+]616.1823,found 616.1818。
Example 15
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, R1Is hydrogen, R2Is 4-trifluoromethylphenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-1(0.3mmol), compound II-5(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 110 ℃ for 15min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 8:1, to give the pure product as a pale yellow solid, yield: 86 percent.
And (3) performing characterization tests on the compound III-15, wherein the characterization tests comprise a melting point test, a nuclear magnetic hydrogen spectrum, a nuclear magnetic carbon spectrum and a high-resolution mass spectrum:
melting point: 81-82 deg.C
1H NMR(400MHz,CDCl3)δ7.79(dd,J＝13.2,7.7Hz,2H),7.75–7.68(m, 1H),7.58(dd,J＝12.1,4.5Hz,2H),7.52(d,J＝8.2Hz,2H),7.49-7.43(m,3H), 7.31(d,J＝8.0Hz,2H),7.29–7.25(m,2H),7.18(d,J＝8.1Hz,2H),7.12(dd,J ＝8.0,5.2Hz,1H)。
13C NMR(100MHz,CDCl3)δ140.62,138.43,138.11,137.60(d,J＝6Hz), 133.28(d,J＝3Hz),133.05,132.63(d,J＝2Hz),132.28(d,J＝10Hz),131.95, 130.77,130.46(d,J＝12Hz),129.68,129.52,128.68,128.50(d,J＝13Hz), 128.44(d,J＝14Hz),126.74(d,J＝9Hz),125.29(q,J＝4Hz),124.90(q,J＝4 Hz),124.68,123.96,122.70,122.48,122.14(d,J＝7Hz),121.98。
31P NMR(162MHz,CDCl3)δ17.78。
HRMS m/z:calcd for C34H18F11NOP[M+H+]696.0945,found 696.0940。
Example 16
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, R1Is hydrogen, R2Is 4-fluorophenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-1(0.3mmol), compound II-6(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 130 ℃ for 20min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 7:1, to give the pure product as a white solid, yield: 87 percent.
Compound III-16 was subjected to characterization tests including melting point test, nuclear magnetic hydrogen spectrum, nuclear magnetic carbon spectrum and high resolution mass spectrometry:
melting point: 177 temperature 178 ℃ C
1H NMR(400MHz,CDCl3)δ7.77(dd,J＝13.1,7.6Hz,2H),7.69(dd,J ＝14.2,7.4Hz,1H),7.54(dd,J＝16.2,8.1Hz,2H),7.48–7.36(m,3H),7.21 –7.07(m,3H),7.02(dd,J＝7.8,5.6Hz,2H),6.94(t,J＝8.6Hz,2H),6.68(t, J＝8.6Hz,2H)。
13C NMR(100MHz,CDCl3)δ163.30,162.95,160.82,160.50,138.75, 138.44(d,J＝5Hz),133.16(d,J＝8Hz),133.03(d,J＝3Hz),132.44(d,J＝2 Hz),132.20(dd,J＝11,1Hz),131.27,131.15(d,J＝8Hz),130.61,130.33(d,J＝ 12Hz),129.30,128.39(d,J＝14Hz),127.43(d,J＝4Hz),126.75(d,J＝10Hz), 123.71,122.45,121.52(d,J＝7Hz),115.13(dd,J＝28,22Hz)。
31P NMR(162MHz,CDCl3)δ17.86。
HRMS m/z:calcd for C32H18F7NOP[M+H+]596.1009,found 596.1028。
Example 17
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, R1Is hydrogen, R2Is 4-chlorophenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-1(0.3mmol), compound II-7(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 110 ℃ for 15min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 3:1, to give the pure product as a tan solid, yield: 90 percent.
And (3) performing characterization tests on the compound III-17, wherein the characterization tests comprise a melting point test, a nuclear magnetic hydrogen spectrum, a nuclear magnetic carbon spectrum and a high-resolution mass spectrum:
melting point: 86-87 deg.C
1H NMR(400MHz,CDCl3)δ7.76(dd,J＝13.2,7.8Hz,2H),7.72–7.66 (m,1H),7.59–7.49(m,2H),7.48–7.39(m,3H),7.24(d,J＝8.4Hz,2H), 7.15(dd,J＝8.0,5.2Hz,1H),7.13–7.06(m,2H),6.98(s,4H)。
13C NMR(100MHz,CDCl3)δ138.42,138.14(d,J＝5Hz),135.44, 134.56,133.55(d,J＝4Hz),133.31,133.10(d,J＝3Hz),132.86,132.49(d,J ＝2Hz),132.22(dd,J＝10,2Hz),130.56,130.40,130.29,129.12,128.58, 128.49,128.36,128.22,127.66,127.52,126.75(d,J＝9Hz),123.82,122.56, 121.64(d,J＝6Hz)。
31P NMR(162MHz,CDCl3)δ17.82。
HRMS m/z:calcd for C32H18Cl2F5NOP[M+H+]628.0418,found 628.0423。
Example 18
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, R1Is hydrogen, R2Is n-propyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-1(0.3mmol), compound II-8(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 100 ℃ for 40min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 6:1, to give the pure product as a pale yellow oily liquid, yield: 51 percent.
Compound III-18 was subjected to characterization tests including melting point test, nuclear magnetic hydrogen spectrum, nuclear magnetic carbon spectrum and high resolution mass spectrum:
1H NMR(400MHz,CDCl3)δ7.86–7.71(m,2H),7.62–7.52(m,2H), 7.52–7.38(m,4H),7.32–7.23(m,1H),2.67–2.38(m,4H),1.76–1.51(m, 4H),1.03(t,J＝7.4Hz,3H),0.94(t,J＝7.4Hz,3H)。
13C NMR(100MHz,CDCl3)δ149.69(d,J＝11Hz),137.49(d,J＝6Hz), 132.53(dd,J＝14,2Hz),132.07,131.96,130.91,130.40(d,J＝13Hz),129.48, 128.33,128.19,126.56(d,J＝15Hz),124.09,123.63(d,J＝10Hz),122.80, 113.76,113.64,33.99(d,J＝5Hz),29.67,22.58,20.16,14.09,13.59.
31P NMR(162MHz,CDCl3)δ23.93。
HRMS m/z:calcd for C26H24F5NOP[M+H+]492.1510,found 492.1507。
example 19
In this embodiment: ArFnIs 1,2,3,4, 5-pentafluorophenyl, a thiophene ring, R2Is phenyl.
The method comprises the following steps: in a 10mL microwave reaction tube, compound I-1(0.3mmol), compound II-8(0.36mmol), Ag was added2CO3(0.6mmol)，NaHCO3(0.36mmol)，[RhCp*Cl2]2(0.012mmol), 1, 2-dichloroethane (3.0mL), the mixture was placed in a microwave reactor at 110 ℃ for 25min and TLC (thin layer chromatography) was used to check the reaction was complete. Carrying out post-treatment purification: cooled to room temperature and concentrated under pressure. The crude product was separated and purified by silica gel column chromatography [ V (petroleum ether): v (ethyl acetate) ═ 5:1, to give the pure product as an off-white solid, yield: 57 percent.
Compound III-19 was subjected to characterization tests including melting point test, nuclear magnetic hydrogen spectrum, nuclear magnetic carbon spectrum and high resolution mass spectrometry:
melting point: 75-76 deg.C
1H NMR(400MHz,CDCl3)δ7.77-7.75(m,1H),7.66(dd,J＝5.9,5.0Hz, 1H),7.59(dd,J＝8.3,3.6Hz,1H),7.24–7.09(m,6H),7.04(d,J＝7.6Hz, 2H),7.00–6.92(m,3H),6.85(dd,J＝4.9,2.7Hz,1H)。
13C NMR(100MHz,CDCl3)δ148.21(d,J＝7Hz),140.12,137.70,137.29 (dd,J＝13,2Hz),135.47,(d,J＝6Hz),134.50(d,J＝4Hz),133.26(d,J＝9Hz), 132.95,131.37,130.88,129.39,128.45,128.28,128.06,127.67,127.33,127.20, 126.97,119.69,118.19(d,J＝5Hz)。
31P NMR(162MHz,CDCl3)δ6.87。
HRMS m/z:calcd for C28H16F5NOPS2[M+H+]572.0326,found 572.0322。
The preparation method can be used for synthesizing the fluorinated cyclic phosphoramide derivative, has simple steps, wide raw material sources, low preparation cost and mild reaction conditions, and has the maximum yield of the fluorinated cyclic phosphoramide derivative reaching 90 percent. The existing synthesis method adopts oil bath heating, the reaction time is short, namely more than ten hours, more than 1-2 days, and the reaction time is long. The preparation method is carried out under the condition of microwave, the reaction time only needs one hour at most, and the reaction time is greatly shortened, so that the heat energy utilization rate is effectively improved. The fluorine-containing cyclic phosphoramide derivative prepared by the preparation method has obvious activity in physiological and pharmacological aspects, and has important significance for developing fluorine-containing organic phosphine medical pesticides.
Finally, it should be noted that the above embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention has been described in detail with reference to examples, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, which should be covered by the claims of the present invention.
Claims (6)
1. The preparation method of the fluoro cyclic phosphonamide derivative is characterized in that the synthetic route is as follows:
wherein, ArFn in the compound I can be 4-fluorophenyl, 3, 5-difluorophenyl, 1,2,3,4, 5-pentafluorophenyl; substituent R1Can be methyl, methoxy, tert-butyl, trifluoromethyl, fluorine, chlorine; substituent R2Can be 4-methylphenyl, 4-methoxyphenyl, 3, 4-dimethylphenyl, 4-trifluoromethylphenyl, 4-fluorophenyl, 4-chlorophenyl or n-propyl.
2. The method for producing a fluorocyclophosphoramide derivative according to claim 1, comprising the steps of:
(1) in a microwave reaction tube, compound I, compound II and Ag2CO3、NaHCO3、[RhCp*Cl2]2Mixing the mixture and 1, 2-dichloroethane, placing the mixture in a microwave reactor, reacting for 5-60 min at 90-140 ℃, and detecting by Thin Layer Chromatography (TLC) until the reaction is complete;
(2) and (2) cooling the product obtained in the step (1) to room temperature, concentrating under reduced pressure, and separating and purifying by silica gel column chromatography to obtain a pure product.
3. The method for producing a fluorocyclophosphonamide derivative according to claim 2, wherein the production is carried out under microwave conditions.
4. The process for producing fluorocyclophosphonic acid amide derivatives according to claim 2, wherein the compound I, the compound II, Ag2CO3、NaHCO3、[RhCp*Cl2]2And the mixed molar ratio of the 1, 2-dichloroethane is 1: (1-3): (1-3): (1-3): (0.01-0.05): (5-10).
5. The preparation method of the fluorocyclophosphoramide derivative according to claim 2, wherein the volume ratio of petroleum ether to ethyl acetate in the silica gel column chromatography is 8:1 to 3: 1.
6. The method for preparing fluorocyclophosphonamide derivatives as claimed in claim 2, wherein the step (2) gives a pure product as a pale yellow solid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911119386.7A CN111116662B (en) | 2019-11-15 | 2019-11-15 | Preparation method of fluoro cyclic phosphonamide derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911119386.7A CN111116662B (en) | 2019-11-15 | 2019-11-15 | Preparation method of fluoro cyclic phosphonamide derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111116662A true CN111116662A (en) | 2020-05-08 |
| CN111116662B CN111116662B (en) | 2022-12-27 |
Family
ID=70495933
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911119386.7A Active CN111116662B (en) | 2019-11-15 | 2019-11-15 | Preparation method of fluoro cyclic phosphonamide derivative |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111116662B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111995642A (en) * | 2020-09-09 | 2020-11-27 | 江汉大学 | Preparation method of phosphine isocoumarin |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150344506A1 (en) * | 2014-05-30 | 2015-12-03 | Knu-Industry Cooperation Foundation | Novel phosphinine oxide derivative and preparation method thereof |
-
2019
- 2019-11-15 CN CN201911119386.7A patent/CN111116662B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150344506A1 (en) * | 2014-05-30 | 2015-12-03 | Knu-Industry Cooperation Foundation | Novel phosphinine oxide derivative and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| NANDINI SHARMA等: ""Microwave-Assisted Ruthenium-Catalysed ortho-C-H Functionalization of N-Benzoyl a-Amino Ester Derivatives"", 《ADV.SYNTH.CATAL.》 * |
| 杨光富 主编: "《有机合成》", 31 August 2016, 上海：华东理工大学出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111995642A (en) * | 2020-09-09 | 2020-11-27 | 江汉大学 | Preparation method of phosphine isocoumarin |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111116662B (en) | 2022-12-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Reddy et al. | Ruthenium-catalyzed aerobic oxidative cyclization of aromatic and heteroaromatic nitriles with alkynes: a new route to isoquinolones | |
| Zhou et al. | Diversity-oriented synthesis of 3-iodochromones and heteroatom analogues via ICl-induced cyclization | |
| Guastavino et al. | Room-Temperature and Transition-Metal-Free Mizoroki–Heck-type Reaction. Synthesis of E-Stilbenes by Photoinduced C–H Functionalization | |
| CN111116662B (en) | Preparation method of fluoro cyclic phosphonamide derivative | |
| Osyanin et al. | Potassium trinitromethanide as a 1, 1-ambiphilic synthon equivalent: access to 2-nitroarenofurans | |
| Wang et al. | Pd (0)-catalyzed cross-coupling of allyl halides with α-diazocarbonyl compounds or N-mesylhydrazones: synthesis of 1, 3-diene compounds | |
| Xie et al. | Palladium (II)-catalyzed synthesis of α-alkylidene-γ-butyrolactams from N-allylic 2-alkynamides. Total synthesis of (±)-isocynodine and (±)-isocynometrine | |
| CN113548999A (en) | Racemic and chiral 3- (2, 3-butadienyl) oxindole compound, preparation method and application | |
| Jin et al. | Synthesis of indeno [1, 2-c] furans via a Pd-catalyzed bicyclization of 2-alkynyliodobenzene and propargylic alcohol | |
| CN110330485B (en) | Indeno isoquinoline compounds and preparation method thereof | |
| CN111620793A (en) | Preparation method of chiral nitrile compound | |
| CN110452267A (en) | The phosphorylated qualone derivative and preparation method and application that a kind of 3- replaces | |
| CN107805253B (en) | Chiral spiro oxidized indole compounds and its synthetic method | |
| CN110382470B (en) | Preparation method of efavirenz | |
| CN107033106B (en) | A kind of preparation method of sulfamide compound | |
| CN109232386A (en) | A kind of method of asymmetric syntheses (S)-preclamol | |
| Zhang et al. | One‐pot Sequential Reaction for the Synthesis of Polysubstituted 3‐(3‐Nitro‐2‐phenylchroman‐4‐yl)‐3‐arylaminoacrylates | |
| Sa et al. | Selective preparation of functionalized dienes from allylic phosphonium salts through the Wittig reaction | |
| Korotaev et al. | Uncatalyzed, highly stereoselective addition of α-morpholinostyrene to 3-nitro-2-(trihalomethyl)-2H-chromenes. Synthesis of trans–cis-and trans–trans-3-nitro-4-phenacyl-(2-trihalomethyl) chromanes | |
| Laidlaw et al. | Synthesis of hycanthone | |
| CN110256401A (en) | A kind of selenizing benzothienyl compounds and its synthetic method | |
| CN105669667A (en) | Trifluoromethyl pyrroloquinoline derivative and synthetic method thereof | |
| CN106749295B (en) | A kind of synthetic method of loop coil Oxoindole gamma-butyrolacton class compound | |
| Meier et al. | Microwave‐assisted synthesis of the (E)‐α‐methylalkenoate framework from multifunctionalized allylic phosphonium salts | |
| CN112851608B (en) | Catalytic oxidation synthesis method of 2-diaryl methyl benzofuran compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |