CN115814849B - Catalyst and method for synthesizing various trisubstituted olefin compounds and heterocyclic compounds - Google Patents
Catalyst and method for synthesizing various trisubstituted olefin compounds and heterocyclic compounds Download PDFInfo
- Publication number
- CN115814849B CN115814849B CN202211494121.7A CN202211494121A CN115814849B CN 115814849 B CN115814849 B CN 115814849B CN 202211494121 A CN202211494121 A CN 202211494121A CN 115814849 B CN115814849 B CN 115814849B
- Authority
- CN
- China
- Prior art keywords
- formula
- compound
- compound shown
- compounds
- mmol
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 31
- 239000003054 catalyst Substances 0.000 title claims abstract description 29
- 150000002391 heterocyclic compounds Chemical class 0.000 title claims abstract description 17
- -1 olefin compounds Chemical class 0.000 title claims abstract description 16
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 230000002194 synthesizing effect Effects 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 191
- 150000003254 radicals Chemical class 0.000 claims abstract description 7
- 238000007342 radical addition reaction Methods 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 150000001336 alkenes Chemical class 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000002887 hydroxy group Chemical class [H]O* 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 32
- 238000006243 chemical reaction Methods 0.000 abstract description 24
- 238000001308 synthesis method Methods 0.000 abstract description 8
- 239000011941 photocatalyst Substances 0.000 abstract description 4
- 230000003197 catalytic effect Effects 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
- 238000005481 NMR spectroscopy Methods 0.000 description 41
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 40
- 230000015572 biosynthetic process Effects 0.000 description 30
- 238000012795 verification Methods 0.000 description 28
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- 239000003208 petroleum Substances 0.000 description 23
- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- 230000005526 G1 to G0 transition Effects 0.000 description 22
- 238000004440 column chromatography Methods 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- 238000003756 stirring Methods 0.000 description 21
- 229910052757 nitrogen Inorganic materials 0.000 description 20
- 238000004821 distillation Methods 0.000 description 16
- 238000010586 diagram Methods 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 239000012230 colorless oil Substances 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000007787 solid Substances 0.000 description 6
- 101001053395 Arabidopsis thaliana Acid beta-fructofuranosidase 4, vacuolar Proteins 0.000 description 5
- 150000002825 nitriles Chemical class 0.000 description 5
- 101001053401 Arabidopsis thaliana Acid beta-fructofuranosidase 3, vacuolar Proteins 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 3
- 238000013375 chromatographic separation Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- 101100132433 Arabidopsis thaliana VIII-1 gene Proteins 0.000 description 1
- 101100459319 Arabidopsis thaliana VIII-2 gene Proteins 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- 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
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
The invention belongs to the field of organic synthesis, and discloses a catalyst and a catalytic method for synthesizing various trisubstituted olefin compounds and heterocyclic compounds, comprising the following steps: under the irradiation of blue light, the compound shown in the formula VII, the compound shown in the formula VIII, the compound shown in the formula IX, the compound shown in the formula X, the compound shown in the formula XI or the compound shown in the formula XII and cyclobutanonoxime ester are subjected to free radical addition reaction in an inert atmosphere to obtain the compound shown in the formula I, the compound shown in the formula II, the compound shown in the formula III, the compound shown in the formula IV, the compound shown in the formula V or the compound shown in the formula VI. The invention utilizes the photocatalyst which is designed independently for the first time, and synthesizes various trisubstituted olefin compounds and heterocyclic compounds under the action of light. Compared with the prior art, the synthesis method of the trisubstituted olefin compound and the heterocyclic compound has the characteristics of easily available raw materials, simplicity in operation, mild reaction conditions, economy, green and the like.
Description
Technical Field
The invention belongs to the field of organic synthesis, and in particular relates to a catalyst and a catalytic method for synthesizing various trisubstituted olefin compounds and heterocyclic compounds.
Background
Nitrile is one of the most useful components for the synthesis of various materials, bioactive molecules and natural products (Wiley-VCH, weinheim,5th compl.rev.edn,1985,vol.A17,p.363). It is highly desirable to develop a fast and efficient process to obtain various nitriles. In this case, the cleavage of carbon-carbon bonds of cyclic ketoxime derivatives has been brought to sp formation since early studies of Zard (J.am.chem.Soc.1991, 113, 1055-1057.) and Uemura (J.am.chem.Soc.2000, 122,12049-12050; J.org.chem.2004,69,5342-5347; org.Lett.2005,7, 2425-2427.) 3 The nitriloalkyl radical to obtain a powerful tool for various nitriles (chem. Soc. Rev.2019,48,2615-2656; acc. Chem. Res.2020,53,1066-1083; chem. Rev.2021,121,264-299; chem. Rev.2021,121, 506-561.). In recent years, visible light photo-oxidative catalysis has been applied under mild conditions to produce nitriloalkyl groups, but these photo-catalytic methods require expensive photocatalysts, transition metal complexes or other additives.
Trisubstituted olefins are important organic synthesis units useful for the synthesis of a wide variety of drugs, materials and fine chemicals (J.Med. Chem.2003,46,1484-1491; anti-cancer drugs 2007,18,1039-1044; nat. Prod. Rep.2014,31, 514-532.). Meanwhile, heterocyclic compounds are very common in natural products and biologically relevant compounds as the main scaffold for drug and pesticide development (J.Med. Chem.2014,57,10257-10274; chem. Rev.2015,115,1622-1651; acc. Chem. Res.2018,51, 1443-1454.). To obtain these compounds, cleavage of the C-C bond of cyclic ketoxime derivatives has become a powerful tool. However, transition metals, photocatalysts and high temperatures are typically necessary for these existing strategies.
In summary, these methods use metals, expensive catalysts or excessive alkali, which are disadvantageous in terms of economy and environmental protection. Therefore, the development of a new catalytic process for economically and environmentally introducing nitrile building blocks into organic molecules is of great importance.
Disclosure of Invention
Aiming at the problems existing in the prior art, the invention provides a method for synthesizing trisubstituted olefin and heterocyclic compounds; the method adopts a brand new organic catalyst to synthesize trisubstituted olefin and heterocyclic compound molecules containing nitrile structural units under the action of light, and provides a simple, efficient, economic and green synthesis way for introducing nitrile compounds into trisubstituted olefin and heterocyclic compounds.
The synthesis method of the trisubstituted olefin compound and the heterocyclic compound provided by the invention, namely the synthesis method of the compound shown in the formula I, the compound shown in the formula II, the compound shown in the formula III, the compound shown in the formula IV, the compound shown in the formula V or the compound shown in the formula VI, comprises the following steps:
under the irradiation of blue light, the compound shown in a formula VII, the compound shown in a formula VIII, the compound shown in a formula IX, the compound shown in a formula X, the compound shown in a formula XI or the compound shown in a formula XII carries out free radical addition reaction with cyclobutanonoxime ester in an inert atmosphere to obtain the compound shown in a formula I, the compound shown in a formula II, the compound shown in a formula III, the compound shown in a formula IV, the compound shown in a formula V or the compound shown in a formula VI;
in the formulas I-VI, R is one of monosubstituted or polysubstituted alkyl, monosubstituted or polysubstituted halogen and hydroxyl;
in the formula VII-XI, R is one of monosubstituted or polysubstituted alkyl, monosubstituted or polysubstituted halogen and hydroxyl.
By way of example, the compounds of formula I are those of formula I-1 to formula I-3:
by way of example, the compounds of formula II are those of formula II-1 to formula II-3:
as an example, the compound represented by formula iii is any one of the compounds represented by the following formula iii-1 to formula iii-3:
as an example, the compound represented by formula IV is any one of the compounds represented by the following formula IV-1 to formula IV-4:
as an example, the compound represented by formula V is any one of the compounds represented by the following formula V-1 to formula V-4:
by way of example, the compound of formula VI is any one of the compounds of formula VI-1 to VI-4 shown below:
in the above synthesis method, the molar ratio of the compound represented by formula VII, the compound represented by formula VIII, the compound represented by formula IX, the compound represented by formula XI, or the compound represented by formula XII to the cyclic ketoxime ester may be 1:1.5.
In the above synthesis method, the concentration of the compound represented by formula VII, the compound represented by formula VIII, the compound represented by formula IX, the compound represented by formula X, the compound represented by formula XI or the compound represented by formula XII in the solvent may be 0.1M.
In the above synthesis method, the wavelength of the blue light may be 450nm; the blue light may be provided by a blue LED lamp, and the power of the LED lamp may be 100W.
In the above synthetic method, the temperature of the free radical addition reaction may be 40 to 50 ℃, specifically 45 ℃; the time may be 12 hours.
In the synthesis method, the method further comprises the steps of performing silica gel chromatographic separation on a system after the reaction is finished, collecting and then performing reduced pressure distillation; preferably, the stationary phase of the silica gel chromatographic separation is SiO 2 The method comprises the steps of carrying out a first treatment on the surface of the The mobile phase is a mixed solution composed of petroleum ether and ethyl acetate in a certain proportion by volume.
Compared with the prior art, the technical scheme of the invention has the following advantages:
the method adopts a novel photocatalyst which is designed independently for the first time, and synthesizes the trisubstituted olefin compound and the heterocyclic compound under the action of light. Compared with the prior art, the synthesis method of the trisubstituted olefin and heterocyclic compound has the characteristics of easily available raw materials, simplicity in operation, mild reaction conditions, economy, green and the like.
Drawings
FIG. 1 is a synthetic scheme of tri-substituted olefins and heterocyclic compounds in accordance with an embodiment of the present invention.
Detailed Description
The present invention will now be described in more detail with reference to the drawings and examples, which are not intended to limit the scope of the invention.
The experimental methods used in the following examples are conventional methods unless otherwise specified. Nuclear magnetic resonance was measured by a japan electron nuclear magnetic resonance apparatus. Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified.
Example 1 Synthesis of Compounds of formula II-1
The compound shown in the formula II-1 is synthesized according to the synthetic route diagram shown in fig. 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula VIII-1 (0.2 mmol), the alkyl ketoxime of formula 3 (0.3 mmol), the catalyst of formula 2 (0.04 mmol) and toluene (2.0 mL) under nitrogen protection. Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate = 5:1, collecting and distilling under reduced pressure to obtain the compound shown in the formula II-1.
The structure verification experimental data are as follows:
colorless oil(49.3mg,0.154mmol,77％). 1 H NMR(400MHz,CDCl 3 )δ7.44–7.36(m,3H),7.31–7.27(m,2H),7.24–7.21(m,3H),7.20–7.16(m,2H),5.19(t,J＝7.6Hz,1H),4.50(s,2H),2.34–2.28(m,2H),2.21(s,3H),2.15(t,J＝7.2Hz,2H),1.67–1.59(m,2H). 13 C NMR(101MHz,CDCl 3 )δ170.5,140.2,137.6,134.6,129.8,129.1,128.9,128.6,128.4,127.5,119.1,49.0,27.4,25.3,22.4,16.6.IR(ATR):2932,2246,1641,1390,1286,1126,777cm - 1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 21 H 22 N 2 ONa + 341.1624,found 341.1621.
the obtained compound is proved to be the compound shown in the formula II-1.
Example 2 Synthesis of Compounds of formula II-2
The compound shown in the formula II-2 is synthesized according to the synthetic route diagram shown in fig. 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula VIII-2 (0.2 mmol), the alkyl ketoxime of formula 3 (0.3 mmol), the catalyst of formula 2 (0.04 mmol) and toluene (2.0 mL) under nitrogen protection. Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=5:1, and the product is obtained after collection and reduced pressure distillation to obtain the compound shown in the formula II-2.
The structure verification experimental data are as follows:
a colorless oil(49.2mg,0.120mmol,60％). 1 H NMR(400MHz,CDCl 3 )δ8.09(d,J＝8.1Hz,2H),7.33–7.23(m,5H),7.20–7.13(m,2H),5.31(d,J＝7.2Hz,1H),4.51(s,2H),4.44–4.38(m,2H),2.35–2.29(m,2H),2.21(s,3H),2.17(t,J＝7.1Hz,2H),1.68–1.61(m,2H),1.42(t,J＝7.1Hz,3H). 13 C NMR(126MHz,CDCl 3 )δ170.5,166.0,139.5,139.1,137.3,131.3,131.0,130.2,129.1,128.6,128.5,127.6,119.0,61.4,49.2,27.5,25.2,22.4,16.7,14.4.IR(ATR):2932,2245,1712,1643,1388,1271,1103,868cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 24 H 26 N 2 O 3 Na + 413.1836,found 413.1826.
the obtained compound is proved to be the compound shown in the formula II-2.
EXAMPLE 3 Synthesis of Compounds of formula II-3
The compound shown in the formula II-3 is synthesized according to the synthetic route diagram shown in fig. 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula VIII-3 (0.2 mmol), the alkyl ketoxime of formula 3 (0.3 mmol), the catalyst of formula 2 (0.04 mmol), and toluene (2.0 mL) under nitrogen protection. Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=5:1, and the product is obtained after collection and reduced pressure distillation to obtain the compound shown in the formula II-3.
The structure verification experimental data are as follows:
a colorless oil(50.4mg,0.154mmol,76％). 1 H NMR(500MHz,CDCl 3 )δ7.31–7.26(m,3H),7.23(d,J＝8.0Hz,2H),7.20–7.16(m,2H),7.13(d,J＝7.9Hz,2H),5.14(t,J＝7.6Hz,1H),4.50(s,2H),2.40(s,3H),2.33–2.29(m,2H),2.21(s,3H),2.15(t,J＝7.1Hz,2H),1.66–1.60(m,2H). 13 C NMR(126MHz,CDCl 3 )δ170.6,140.2,139.2,137.7,131.6,129.6,129.23,129.15,128.6,128.4,127.5,119.2,48.9,27.5,25.4,22.4,21.4,16.7.IR(ATR):2927,2246,1640,1390,1167,819cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 22 H 24 N 2 ONa + 355.1781,found 355.1776.
the obtained compound is proved to be the compound shown in the formula II-3.
EXAMPLE 4 Synthesis of Compounds of formula III-1
The compound shown in the formula III-1 is synthesized according to the synthesis route diagram shown in FIG. 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula IX-1 (0.2 mmol), the alkyl ketoxime of formula 3 (0.3 mmol), and the catalyst of formula 2 (0.04 mmol), dimethyl sulfoxide (2.0 mL) under nitrogen protection. Stirring at 45deg.C on a 100W blue LED (450 nm) lampNight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=4:1, and then the petroleum ether/ethyl acetate=4:1 is collected and distilled under reduced pressure to obtain a product, so as to obtain a compound shown in a formula III-1.
The structure verification experimental data are as follows:
a white solid(32.8mg,0.154mmol,77％). 1 H NMR(400MHz,CDCl 3 )δ7.61(s,1H),7.56–7.44(m,2H),7.37–7.27(m,2H),2.76(t,J＝7.0Hz,2H),2.44(t,J＝7.0Hz,2H),2.10–2.02(m,2H). 13 C NMR(101MHz,CDCl 3 ) Delta 161.6,153.5,140.3,131.3,127.6,127.3,124.7,119.3,116.7,30.4,23.8,16.9 (iii-1 was synthesized according to literature report procedures to give Yu, y.z.; ye, z.p.; xia, p.j.; song, d.; li, X.J.; liu, z.l.; liu, f; chen, k; xiang, h.y.; yang, H., J.Org.chem.2021,86, 4245-4253).
The obtained compound is proved to be the compound shown in the formula III-1.
Example 5 Synthesis of Compounds of formula III-2
The compound shown in the formula III-2 is synthesized according to the synthetic route diagram shown in FIG. 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula IX-2 (0.2 mmol), the alkyl ketoxime of formula 3 (0.3 mmol), and the catalyst of formula 2 (0.04 mmol), dimethyl sulfoxide (2.0 mL) under nitrogen protection. Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=4:1, and the product is obtained by reduced pressure distillation after collection to obtain the compound shown in the formula III-2.
The structure verification experimental data are as follows:
a white solid(27.5mg,0.114mmol,57％). 1 H NMR(400MHz,CDCl 3 )δ7.54(s,1H),7.36(d,J＝8.6Hz,1H),6.87–6.84(m,1H),6.82(d,J＝2.4Hz,1H),3.87(s,3H),2.70(t,J＝7.0Hz,2H),2.42(t,J＝7.0Hz,2H),2.07–2.02(m,2H). 13 CNMR(101MHz,CDCl 3 ) Delta 162.4,161.9,155.2,140.5,128.5,123.5,119.4,112.9,112.8,100.6,55.9,30.2,23.9,16.8 (iii-1 was synthesized according to literature report procedures to give Yu, y.z.; ye, z.p.; xia, p.j.; song, d.; li, X.J.; liu, z.l.; liu, f; chen, k; xiang, h.y.; yang, H., J.Org.chem.2021,86, 4245-4253).
The obtained compound is proved to be the compound shown in the formula III-2.
Example 6 Synthesis of Compounds of formula III-3
The compound shown in the formula III-3 is synthesized according to the synthetic route diagram shown in FIG. 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula IX-3 (0.2 mmol), the alkyl ketoxime of formula 3 (0.3 mmol), and the catalyst of formula 2 (0.04 mmol), dimethyl sulfoxide (2.0 mL) under nitrogen protection. Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=4:1, and the product is obtained after collection and reduced pressure distillation to obtain the compound shown in the formula III-3.
The structure verification experimental data are as follows:
a white solid(24.3mg,0.106mmol,53％). 1 H NMR(400MHz,CD 3 CN)δ7.75(s,1H),7.61(s,1H),7.40(d,J＝8.5Hz,1H),6.82–6.72(m,2H),2.61–2.53(m,2H),2.44(t,J＝7.2Hz,2H),1.94–1.86(m,2H). 13 C NMR(126MHz,CD 3 CN) delta 162.5,160.6,155.8,140.9,129.8,124.3,121.0,113.6,103.0,30.4,24.5,16.9 (iii-1 was synthesized according to literature report procedures to give Gao, p;Cheng,Y.B.；Yang,F.；Guo,L.N.；Duan,X.H.,TetrahedronLett.2019,60,150967).
the obtained compound is proved to be the compound shown in the formula III-3.
EXAMPLE 7 Synthesis of Compounds of formula IV-1
The compound shown in the formula IV-1 is synthesized according to the synthetic route diagram shown in fig. 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula X-1 (0.2 mmol), the alkyl ketoxime of formula 3 (0.3 mmol), the catalyst of formula 2 (0.04 mmol) and acetone (2.0 mL) under nitrogen protection. Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=5:1, and collecting and then decompressing and distilling to obtain a product so as to obtain a compound shown in a formula IV-1.
The structure verification experimental data are as follows:
a colorless oil(43.7mg,0.162mmol,81％). 1 H NMR(400MHz,CDCl 3 )δ8.25(d,J＝7.3Hz,1H),7.68–7.64(m,1H),7.49–7.38(m,2H),3.38(s,3H),2.41–2.27(m,1H),2.25–2.12(m,2H),1.94–1.87(m,1H),1.61(s,3H),1.58–1.44(m,2H),1.11–0.86(m,2H). 13 C NMR(101MHz,CDCl 3 ) Delta 176.5,164.4,143.1,134.4,129.2,127.7,125.2,125.0,119.3,47.7,41.8,29.8,27.3,25.4,24.6,16.9 (iv-1 was synthesized according to literature report procedure to give Wang, z.; yan, x.y.; he, x.x.; yan, x.h.; li, X.Q.; xu, x.s., synlett2020,31, 809-812).
The obtained compound is proved to be the compound shown in the formula IV-1.
Example 8 Synthesis of Compounds of formula IV-2
The compound of formula IV-2 was synthesized according to the synthetic scheme shown in FIG. 1, and the specific steps are as follows:
the pre-dried reaction tube is put in nitrogenAfter the compound represented by the formula X-2 (0.2 mmol), the alkyl ketoxime represented by the formula 3 (0.3 mmol), the catalyst represented by the formula 2 (0.04 mmol) and acetone (2.0 mL) were added under protection. Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=5:1, and collecting and then decompressing and distilling to obtain a product so as to obtain a compound shown in a formula IV-2.
The structure verification experimental data are as follows:
a colorless oil(40.9mg,0.136mmol,68％). 1 H NMR(500MHz,CDCl 3 )δ8.21(d,J＝8.8Hz,1H),6.98–6.96(m,1H),6.85(s,1H),3.91(s,3H),3.37(s,3H),2.38–2.27(m,1H),2.24–2.14(m,2H),1.90–1.84(m,1H),1.60(s,3H),1.59–1.46(m,2H),1.11–0.90(m,2H). 13 C NMR(126MHz,CDCl 3 ) Delta 176.6,164.5,164.0,145.4,131.5,119.4,118.0,113.3,110.5,55.7,47.9,41.9,29.9,27.2,25.4,24.5,16.9 (iv-2 was synthesized according to literature report procedure to give Wang, z.; yan, x.y.; he, x.x.; yan, x.h.; li, X.Q.; xu, x.s., synlett2020,31,809-812).
The obtained compound is proved to be the compound shown in the formula IV-2.
Example 9 Synthesis of Compounds of formula IV-3
The compound of formula IV-3 was synthesized according to the synthetic scheme shown in FIG. 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula X-3 (0.2 mmol), the alkyl ketoxime of formula 3 (0.3 mmol), the catalyst of formula 2 (0.04 mmol) and acetone (2.0 mL) under nitrogen protection. Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=5:1, and collecting and then decompressing and distilling to obtain a product so as to obtain a compound shown in a formula IV-3.
The structure verification experimental data are as follows:
a yellow oil(34.6mg,0.102mmol,51％). 1 H NMR(400MHz,CDCl 3 )δ8.30(s,1H),7.67(s,1H),3.41(s,3H),2.93–2.81(m,1H),2.35–2.21(m,3H),1.82(s,3H),1.64–1.47(m,2H),1.05–0.77(m,2H). 13 C NMR(126MHz,CDCl 3 )δ176.2,162.2,137.3,137.0,134.6,133.3,128.7,119.3,49.2,36.8,28.0,25.7,25.3,25.0,16.9.IR(ATR):2940,2246,1715,1665,1324,1271,1117,775cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 16 H 16 Cl 2 N 2 O 2 Na + 361.0481,found 361.0479.
the obtained compound is proved to be the compound shown in the formula IV-3.
Example 10 Synthesis of Compounds of formula IV-4
The compound of formula IV-4 was synthesized according to the synthetic scheme shown in FIG. 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula X-4 (0.2 mmol), the alkyl ketoxime of formula 3 (0.3 mmol), the catalyst of formula 2 (0.04 mmol) and acetone (2.0 mL) under nitrogen protection. Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=5:1, and collecting and then decompressing and distilling to obtain a product so as to obtain a compound shown in a formula IV-4.
The structure verification experimental data are as follows:
a colorless oil(55.0mg,0.160mmol,80％). 1 H NMR(400MHz,CDCl 3 )δ8.27(d,J＝8.0Hz,1H),7.67–7.63(m,1H),7.49–7.37(m,4H),7.33–7.26(m,2H),7.25–7.21(m,1H),5.26(d,J＝13.4Hz,1H),5.15(d,J＝13.7Hz,1H),2.32–2.20(m,1H),2.12–1.97(m,2H),1.93–1.81(m,1H),1.60(s,3H),1.48–1.35(m,2H),0.93–0.76(m,2H). 13 C NMR(101MHz,CDCl 3 ) Delta 176.1,164.1,143.2,137.2,134.4,129.3,128.9,128.5,127.7,127.6,125.1,125.0,119.3,47.6,43.6,42.1,29.3,25.3,24.3,16.8 (iv-4 was synthesized according to literature report procedure to give Wang, z.; yan, x.y.; he, x.x.; yan, x.h.; li, X.Q.; xu, x.s., synlett2020,31,809-812.)
The obtained compound is proved to be the compound shown in the formula IV-4.
Example 11 Synthesis of the Compounds shown in V-1
The compound shown as V-1 is synthesized according to the synthetic route diagram shown in FIG. 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula XI-1 (0.2 mmol), the alkyl ketoxime of formula 3 (0.3 mmol), the catalyst of formula 2 (0.04 mmol), and tetrahydrofuran (2.0 mL) under nitrogen protection. Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=3:1, and then the product is obtained by reduced pressure distillation after collection, so as to obtain the compound shown in the formula V-1.
The structure verification experimental data are as follows:
a colorless oil(45.5mg,0.138mmol,69％). 1 H NMR(400MHz,CDCl 3 )δ8.53–8.46(m,1H),7.88–7.78(m,1H),7.65–7.56(m,1H),7.53–7.50(m,1H),7.48(d,J＝3.7Hz,1H),7.47–7.41(m,3H),2.51–2.43(m,1H),2.25–2.10(m,2H),2.10–2.00(m,1H),1.73(s,3H),1.61–1.48(m,2H),1.16–0.94(m,2H). 13 CNMR(101MHz,CDCl 3 )δ173.1,149.8,144.2,141.2,132.3,131.4,128.1,126.21,126.17,126.0,125.8,123.1,120.0,119.3,115.8,49.4,41.6,29.5,25.5,24.7,16.9.IR(ATR):2931,2245,1712,1613,1583,1450,1352,1166,962,742cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 21 H 19 N 3 ONa + 352.1420,found 352.1417.
the obtained compound is proved to be the compound shown in the formula V-1.
Example 12 Synthesis of Compounds of formula V-2
The compound of formula V-2 was synthesized according to the synthetic scheme shown in FIG. 1, and the specific procedure is as follows:
the previously dried reaction tube was charged with the compound of formula XI-2 (0.2 mmol), the alkyl ketoxime of formula 3 (0.3 mmol), the catalyst of formula 2 (0.04 mmol), and tetrahydrofuran (2.0 mL) under nitrogen protection. Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=3:1, and the product is obtained by reduced pressure distillation after collection to obtain the compound shown in the formula V-2.
The structure verification experimental data are as follows:
a white solid(47.2mg,0.116mmol,58％). 1 H NMR(400MHz,CDCl 3 )δ8.42–8.34(m,1H),7.95–7.92(m,1H),7.85–7.82(m,1H),7.49–7.45(m,3H),7.40–7.36(m,1H),2.51–2.39(m,1H),2.27–2.08(m,2H),2.08–1.96(m,1H),1.73(s,3H),1.63–1.44(m,2H),1.05(m,2H). 13 C NMR(126MHz,CDCl 3 )δ172.1,147.2,144.2,143.7,135.5,131.6,130.7,126.6,126.2,125.5,122.5,121.7,121.0,119.3,115.8,49.7,41.9,29.6,25.4,24.5,16.9.IR(ATR):2925,2245,1704,1562,1447,1329,1125,966,749cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 21 H 18 BrN 3 ONa + 430.0526,found 430.0519.
the obtained compound is proved to be the compound shown as the formula V-2.
Example 13 Synthesis of Compounds of formula V-3
The compound of formula V-3 was synthesized according to the synthetic scheme shown in FIG. 1, and the specific procedure is as follows:
the previously dried reaction tube was charged with the compound of formula XI-3 (0.2 mmol), the alkyl ketoxime of formula 3 (0.3 mmol), the catalyst of formula 2 (0.04 mmol), and tetrahydrofuran (2.0 mL) under nitrogen protection. Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=3:1, and the product is obtained by reduced pressure distillation after collection to obtain the compound shown in the formula V-3.
The structure verification experimental data are as follows:
a colorless oil(53.3mg,0.150mmol,75％). 1 H NMR(400MHz,CDCl 3 )δ8.37–8.30(m,2H),7.81(d,J＝8.1Hz,1H),7.50–7.38(m,2H),7.21(s,1H),2.60(s,3H),2.50–2.46(m,2H),2.42(s,3H),2.25–2.08(m,2H),1.81(s,3H),1.64–1.46(m,2H),1.09–0.94(m,2H). 13 C NMR(126MHz,CDCl 3 )δ174.3,150.6,144.4,138.1,137.9,136.0,135.5,131.4,126.2,125.5,125.4,123.7,119.8,119.3,115.9,50.6,38.0,26.7,25.6,25.2,23.0,20.7,16.9.IR(ATR):2922,2245,1722,1540,1450,1364,1324,1121,863,772cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 23 H 23 N 3 ONa + 380.1733,found 380.1728.
the obtained compound is proved to be the compound shown as the formula V-3.
Example 14 Synthesis of Compounds of formula V-4
The compound of formula V-4 was synthesized according to the synthetic scheme shown in FIG. 1, and the specific procedure is as follows:
the previously dried reaction tube was charged with the compound of formula XI-4 (0.2 mmol), the alkyl ketoxime of formula 3 (0.3 mmol) and the catalyst of formula 2 (0.04 mmol) under nitrogen protection,tetrahydrofuran (2.0 mL). Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=3:1, and the product is obtained by reduced pressure distillation after collection to obtain the compound shown in the formula V-4.
The structure verification experimental data are as follows:
a white solid(45.0mg,0.110mmol,55％). 1 H NMR(400MHz,CDCl 3 )δ8.47–8.45(m,1H),8.21(d,J＝8.5Hz,1H),7.96(d,J＝1.8Hz,1H),7.64–7.60(m,1H),7.55–7.49(m,2H),7.48–7.47(m,1H),2.48–2.42(m,1H),2.25–2.10(m,2H),2.08–2.02(m,1H),1.73(s,3H),1.64–1.45(m,2H),1.13–0.95(m,2H). 13 CNMR(126MHz,CDCl 3 )δ173.0,150.8,145.6,141.4,132.6,130.4,128.7,128.2,126.4,126.0,123.0,122.7,119.2,116.9,49.5,41.6,29.5,25.4,24.6,16.9.IR(ATR):2926,2242,1705,1604,1578,1445,1347,1325,1157,969,776cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 21 H 18 BrN 3 ONa + 430.0526,found 430.0522.
the obtained compound is proved to be the compound shown as the formula V-4.
EXAMPLE 15 Synthesis of Compounds of formula VI-1
The compound shown in the formula VI-1 is synthesized according to the synthesis route diagram shown in FIG. 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula XII-1 (0.2 mmol), the alkyl ketoxime of formula 4 (0.3 mmol) and the catalyst of formula 2 (0.04 mmol) under nitrogen protection, followed by dimethyl sulfoxide (2.0 mL). Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=3:1, and the product is obtained by reduced pressure distillation after collectionA compound of formula VI-1.
The structure verification experimental data are as follows:
a colorless oil(isolated as an inseparable mixture,dr＝1:1,55.9mg,0.178mmol,89％). 1 H NMR(400MHz,CDCl 3 )δ7.31–7.27(m,2H),7.16(d,J＝7.3Hz,2H),7.10–7.07(m,2H),6.86(d,J＝7.8Hz,2H),4.20–4.14(m,4H),3.22(d,J＝1.2Hz,6H),2.66–2.40(m,6H),1.99–1.85(m,2H),1.85–1.70(m,2H),1.51–1.42(m,1H),1.36(d,J＝2.6Hz,6H),1.34–1.24(m,9H). 13 C NMR(126MHz,CDCl 3 )δ180.07,180.02,172.3,172.2,143.4,143.3,133.21,133.15,128.27,128.25,122.94,122.91,122.60,122.58,117.7,117.6,108.4,61.6,48.1,48.0,41.6,41.5,35.0,34.8,26.5,26.4,26.3,24.02,23.92,19.5,19.1,14.3.IR(ATR):2928,2247,1700,1612,1471,1421,1376,1181,1125,935,755cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 18 H 22 N 2 O 3 Na + 337.1523,found 337.1517.
proved by verification, the obtained compound is the compound shown in the formula VI-1.
EXAMPLE 16 Synthesis of Compounds of formula VI-2
The compound shown in the formula VI-2 is synthesized according to the synthetic route diagram shown in FIG. 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula XII-1 (0.2 mmol), the alkyl ketoxime of formula 5 (0.3 mmol) and the catalyst of formula 2 (0.04 mmol) under nitrogen protection, followed by dimethyl sulfoxide (2.0 mL). Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=3:1, and the product is obtained by reduced pressure distillation after collection to obtain the compound shown in the formula VI-2.
The structure verification experimental data are as follows:
a colorless oil(isolated as an inseparable mixture,dr＝1:1,49.2mg,0.154mmol,77％). 1 H NMR(400MHz,CDCl 3 )δ7.37–7.26(m,8H),7.18–7.02(m,7H),6.97–6.96(m,1H),6.88–6.85(m,2H),3.22(d,J＝6.5Hz,6H),2.87–2.68(m,2H),2.50–2.42(m,4H),1.91–1.60(m,4H),1.57–1.33(m,4H),1.28(d,J＝11.3Hz,6H). 13 C NMR(126MHz,CDCl 3 )δ180.4,180.2,143.3,143.2,141.0,140.8,133.6,133.4,129.03,129.01,128.1,127.64,127.59,127.3,127.2,122.8,122.7,122.5,122.4,118.3,108.2,48.12,48.06,42.3,42.2,35.8,35.7,29.5,29.3,25.5,25.1,24.1,23.9.IR(ATR):2925,2245,1702,1611,1492,1453,1348,1066,753cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 21 H 22 N 2 ONa + 341.1624,found 341.1618.
proved by verification, the obtained compound is the compound shown in the formula VI-2.
EXAMPLE 17 Synthesis of Compounds of formula VI-3
The compound shown in the formula VI-3 is synthesized according to the synthetic route diagram shown in FIG. 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula XII-1 (0.2 mmol), the alkyl ketoxime of formula 6 (0.3 mmol) and the catalyst of formula 2 (0.04 mmol) under nitrogen protection, followed by dimethyl sulfoxide (2.0 mL). Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=3:1, and the product is obtained by reduced pressure distillation after collection to obtain the compound shown in the formula VI-3.
The structure verification experimental data are as follows:
a colorless oil(isolated as an inseparable mixture,dr＝1:1,52.2mg,0.150mmol,75％). 1 H NMR(500MHz,CDCl 3 )δ7.31–7.27(m,5H),7.25–7.24(m,1H),7.20(d,J＝7.4Hz,1H),7.17–7.04(m,3H),6.99–6.92(m,2H),6.87(d,J＝7.8Hz,2H),6.85–6.80(m,4H),3.94–3.90(m,2H),3.81–3.78(m,1H),3.76–3.69(m,1H),3.23(d,J＝4.7Hz,6H),2.50–2.47(m,4H),2.11–1.94(m,4H),1.91–1.79(m,2H),1.37(d,J＝5.6Hz,6H),1.28–1.06(m,4H). 13 C NMR(126MHz,CDCl 3 )δ180.34,180.32,158.5,158.4,143.4,143.3,133.4,133.3,129.7,128.22,128.19,123.0,122.9,122.7,122.6,121.4,118.3,118.1,114.68,114.65,108.4,68.8,68.2,48.25,48.22,35.9,35.8,35.4,26.4,25.6,25.5,24.2,24.0,19.8,19.4.IR(ATR):2926,2245,1702,1611,1492,1469,1238,1124,1018,749cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 22 H 24 N 2 O 2 Na + 371.1730,found 371.1723.
proved by verification, the obtained compound is the compound shown in the formula VI-3.
EXAMPLE 18 Synthesis of Compounds of formula VI-4
The compound shown in the formula VI-4 is synthesized according to the synthetic route diagram shown in FIG. 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula XII-1 (0.2 mmol), the alkyl ketoxime of formula 7 (0.3 mmol) and the catalyst of formula 2 (0.04 mmol) under nitrogen protection, followed by dimethyl sulfoxide (2.0 mL). Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=3:1, and the product is obtained after collection and reduced pressure distillation to obtain the compound shown in the formula VI-4.
The structure verification experimental data are as follows:
a white solid(isolated as an inseparable mixture,dr＝1.3:1,33.9mg,0.102mmol,51％). 1 H NMR(400MHz,CDCl 3 )7.36–7.32(m,1H),7.31–7.27(m,1H),7.23–7.11(m,8H),7.01–6.97(m,1H),6.93–6.90(m,2H),6.87–6.78(m,3H),6.77–6.73(m,2H),3.25(d,J＝7.5Hz,6H),2.49(dd,J＝13.9,4.1Hz,1H),2.33–1.91(m,9H),1.89–1.80(m,2H),1.73–1.59(m,1H),1.53–1.40(m,3H),1.38(s,3H),1.31(s,3H),1.28–1.21(m,1H),1.17–1.07(m,1H). 13 C NMR(126MHz,CDCl 3 )δ180.73,180.68,143.4,143.3,139.7,139.6,133.4,133.0,129.1,129.0,128.6,128.5,128.4,128.2,126.3,123.1,123.0,122.8,119.8,119.5,108.54,108.45,48.2,47.8,41.8,41.7,41.0,40.3,36.3,36.2,29.5,29.4,26.49,26.45,25.8,25.2,14.6,14.5.IR(ATR):2927,2247,1688,1612,1525,1449,1364,1254,1164,1017,745cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 22 H 24 N 2 ONa + 355.1781,found355.1775.
proved by verification, the obtained compound is the compound shown in the formula VI-4.
EXAMPLE 19 Synthesis of Compounds of formula I-1
The compound shown in the formula I-1 is synthesized according to the synthesis route diagram shown in fig. 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula VII-1 (0.2 mmol), the alkyl ketoxime of formula 3 (0.3 mmol), the catalyst of formula 2 (0.04 mmol) and acetone (2.0 mL) under nitrogen protection. Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=3:1, and the product is obtained after collection and reduced pressure distillation to obtain the compound shown in the formula I-1.
The structure verification experimental data are as follows:
a colorless oil(36.1mg,0.146mmol,73％). 1 H NMR(400MHz,CDCl 3 )δ7.40–7.35(m,2H),7.34–7.31(m,1H),7.29–7.18(m,5H),7.18–7.12(m,2H),6.01(t,J＝7.4Hz,1H),2.31–2.23(m,4H),1.83–1.75(m,2H). 13 C NMR(101MHz,CDCl 3 ) Delta 143.8,142.2,139.7,129.8,128.5,128.3,127.3,127.3,126.7,119.7,28.8,25.8,16.8 (i-1 was synthesized according to literature report procedure to give Zhao, b.; shi, z., angel. Chem. Int. Ed.2017,56, 12727-12731.)
The obtained compound is the compound shown as I-1 through verification.
EXAMPLE 20 Synthesis of Compounds of formula I-2
The compound shown in the formula I-2 is synthesized according to the synthesis route diagram shown in fig. 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula VII-2 (0.2 mmol), the alkyl ketoxime of formula 3 (0.3 mmol), the catalyst of formula 2 (0.04 mmol) and acetone (2.0 mL) under nitrogen protection. Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=3:1, and the product is obtained after collection and reduced pressure distillation to obtain the compound shown in the formula I-2.
The structure verification experimental data are as follows:
a colorless oil(42.3mg,0.150mmol,75％). 1 H NMR(500MHz,CDCl 3 )δ7.17–7.14(m,2H),7.13–7.04(m,4H),6.98–6.94(m,2H),5.95(t,J＝7.4Hz,1H),2.32(t,J＝7.2Hz,2H),2.28–2.24(m,2H),1.83–1.77(m,2H). 13 C NMR(126MHz,CDCl 3 ) Delta 162.4 (d, j=248.2 Hz), 162.2 (d, j=248.2 Hz), 142.0,138.3 (d, j=3.4 Hz), 135.4 (d, j=3.5 Hz), 131.4 (d, j=7.9 Hz), 128.9 (d, j=7.9 Hz), 127.0,119.5,115.6 (d, j=21.3 Hz), 115.2 (d, j=21.5 Hz), 28.8,25.8,16.9 (i-2 synthesized according to literature reporter procedures to give Yu, x.y.; chen, j.r.; wang, p.z.; yang, m.n.; liang, D.; xiao, W.J., angew.Chem.Int.Ed.2018,57, 738-743.)
The obtained compound is the compound shown as I-2 through verification.
Example 21 Synthesis of Compounds of formula I-3
The compound shown in the formula I-3 is synthesized according to the synthesis route diagram shown in figure 1, and the specific steps are as follows:
the previously dried reaction tube was charged with the compound of formula VII-3 (0.2 mmol), the alkyl ketoxime of formula 3 (0.3 mmol), the catalyst of formula 2 (0.04 mmol) and acetone (2.0 mL) under nitrogen protection. Stir over a 100W blue LED (450 nm) lamp at 45℃overnight (12 h). The reaction mixture was then distilled under reduced pressure and chromatographed on silica gel (stationary phase of column chromatography: siO) 2 Mobile phase: petroleum ether/ethyl acetate=3:1, and the product is obtained after collection and reduced pressure distillation to obtain the compound shown in the formula I-3.
The structure verification experimental data are as follows:
a colorless oil(46.8mg,0.152mmol,76％). 1 H NMR(500MHz,CDCl 3 )δ7.17–7.11(m,2H),7.10–7.03(m,2H),6.94–6.87(m,2H),6.83–6.77(m,2H),5.87(t,J＝7.4Hz,1H),3.83(s,3H),3.78(s,3H),2.30(t,J＝7.3Hz,2H),2.28–2.23(m,2H),1.81–1.75(m,2H). 13 C NMR(126MHz,CDCl 3 )δ159.1,158.8,142.9,135.4,132.3,131.0,128.5,124.8,119.8,113.8,113.6,55.40,55.36,28.8,26.0,16.8.IR(ATR):2934,2246,1604,1508,1241,1170,1028,832cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 20 H 21 NO 2 Na + 330.1465,found 330.1461.
the obtained compound is the compound shown as I-3 through verification.
Although the foregoing embodiments have been described in some, but not all, embodiments of the invention, it should be understood that other embodiments may be devised in accordance with the present embodiments without departing from the spirit and scope of the invention.
Claims (7)
1. A method for introducing nitrile compounds into trisubstituted olefin and/or heterocyclic compounds is characterized in that under blue light irradiation, a raw material, an organic catalyst and cyclobutanone oxime ester are subjected to free radical addition reaction to obtain trisubstituted olefin and/or heterocyclic compounds introduced with nitrile compounds; the structural formula of the organic catalyst is shown as formula 2;
formula 2;
the raw materials comprise a compound shown in a formula VII, a compound shown in a formula VIII, a compound shown in a formula IX, a compound shown in a formula X, a compound shown in a formula XI or a compound shown in a formula XII;
in the formula VII-XI, R is one of monosubstituted or polysubstituted alkyl, monosubstituted or polysubstituted halogen and hydroxyl.
2. The method according to claim 1, wherein the trisubstituted olefin compound and/or heterocyclic compound introduced with the nitrile compound comprises a compound represented by formula i, a compound represented by formula ii, a compound represented by formula iii, a compound represented by formula iv, a compound represented by formula v or a compound represented by formula vi;
in the formula I-VI, R is one of monosubstituted or polysubstituted alkyl, monosubstituted or polysubstituted halogen and hydroxyl.
3. The method of claim 1, wherein the free radical addition reaction is performed in an inert atmosphere.
4. The method of claim 1, wherein the molar ratio of starting material to cyclic ketoxime ester is 1:1.5.
5. The method according to claim 1 or 4, wherein the concentration of the starting material in the solvent is 0.1M.
6. The method of claim 4, wherein the blue light has a wavelength of 450-456 nm.
7. The method according to claim 1, wherein the free radical addition reaction is carried out at a temperature of 40 to 50 ℃ for a period of 12 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211494121.7A CN115814849B (en) | 2022-11-25 | 2022-11-25 | Catalyst and method for synthesizing various trisubstituted olefin compounds and heterocyclic compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211494121.7A CN115814849B (en) | 2022-11-25 | 2022-11-25 | Catalyst and method for synthesizing various trisubstituted olefin compounds and heterocyclic compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115814849A CN115814849A (en) | 2023-03-21 |
| CN115814849B true CN115814849B (en) | 2024-03-08 |
Family
ID=85531778
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211494121.7A Active CN115814849B (en) | 2022-11-25 | 2022-11-25 | Catalyst and method for synthesizing various trisubstituted olefin compounds and heterocyclic compounds |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115814849B (en) |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6403521B1 (en) * | 1999-09-01 | 2002-06-11 | Daicel Chemical Industries, Ltd. | Catalyst comprising nitrogen-containing heterocyclic compound, and process for producing organic compound using the catalyst |
| CN102229574A (en) * | 2011-04-26 | 2011-11-02 | 同济大学 | 3-benzotriazole-substituted-1-(1,3-diaryl) propylene compound, synthesis method and use thereof |
| CN104250231A (en) * | 2014-09-18 | 2014-12-31 | 陕西煤业化工技术开发中心有限责任公司 | Benzotriazole ionic liquid for synthesizing methylbenzene diamido-formic alkyl ester |
| CN104292172A (en) * | 2014-09-12 | 2015-01-21 | 浙江理工大学 | Benzotriazole derivative and preparation method thereof |
| WO2017173975A1 (en) * | 2016-04-06 | 2017-10-12 | 中国科学院福建物质结构研究所 | Method for synthesizing compound containing non-terminal double bond |
| CN109134392A (en) * | 2018-10-08 | 2019-01-04 | 周口师范学院 | N2-alkenyl benzotriazole derivative and synthetic method thereof |
| CN110483406A (en) * | 2019-08-27 | 2019-11-22 | 浙江工业大学 | A method of the synthesis class of difluoromethyl containing N- compound |
| CN110563535A (en) * | 2019-08-28 | 2019-12-13 | 浙江工业大学 | method for synthesizing 1, 2-disubstituted olefin compound by alkyne alkylation |
| CN114835652A (en) * | 2022-06-02 | 2022-08-02 | 河南大学 | Method for synthesizing imido benzotriazole compound under photocatalysis condition |
-
2022
- 2022-11-25 CN CN202211494121.7A patent/CN115814849B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6403521B1 (en) * | 1999-09-01 | 2002-06-11 | Daicel Chemical Industries, Ltd. | Catalyst comprising nitrogen-containing heterocyclic compound, and process for producing organic compound using the catalyst |
| CN102229574A (en) * | 2011-04-26 | 2011-11-02 | 同济大学 | 3-benzotriazole-substituted-1-(1,3-diaryl) propylene compound, synthesis method and use thereof |
| CN104292172A (en) * | 2014-09-12 | 2015-01-21 | 浙江理工大学 | Benzotriazole derivative and preparation method thereof |
| CN104250231A (en) * | 2014-09-18 | 2014-12-31 | 陕西煤业化工技术开发中心有限责任公司 | Benzotriazole ionic liquid for synthesizing methylbenzene diamido-formic alkyl ester |
| WO2017173975A1 (en) * | 2016-04-06 | 2017-10-12 | 中国科学院福建物质结构研究所 | Method for synthesizing compound containing non-terminal double bond |
| CN109134392A (en) * | 2018-10-08 | 2019-01-04 | 周口师范学院 | N2-alkenyl benzotriazole derivative and synthetic method thereof |
| CN110483406A (en) * | 2019-08-27 | 2019-11-22 | 浙江工业大学 | A method of the synthesis class of difluoromethyl containing N- compound |
| CN110563535A (en) * | 2019-08-28 | 2019-12-13 | 浙江工业大学 | method for synthesizing 1, 2-disubstituted olefin compound by alkyne alkylation |
| CN114835652A (en) * | 2022-06-02 | 2022-08-02 | 河南大学 | Method for synthesizing imido benzotriazole compound under photocatalysis condition |
Non-Patent Citations (1)
| Title |
|---|
| Sean McIlroy et al.，.Singlet-Triplet Energy Gaps in Highly Stabilized Nitrenium Ions: Experimental and Theoretical Study of 1,3-Dimethylbenzotriazolium Ion.《Org. Lett.》.2000,第2卷(第6期),全文. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115814849A (en) | 2023-03-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Tang et al. | Ytterbium pentafluorobenzoate as a novel fluorous Lewis acid catalyst in the synthesis of 2, 4-disubstituted quinolines | |
| Adib et al. | Reaction between anthranilic acids, salicylaldehydes and isocyanides in water: an efficient synthesis of 2-{[2-(alkylimino)-1-benzofuran-3-yliden] amino} benzoic acids | |
| CN108558692B (en) | Preparation method of amide compound | |
| Jin et al. | Palladium (II)-catalyzed switchable mono-/diselenylation of arenes controlled by solvent effects | |
| CN116120253A (en) | Benzoxazine compound and synthetic method and application thereof | |
| CN110041235B (en) | N-phenyl-N-p-toluenesulfonyl trifluoroacetamide and application thereof | |
| CN115814849B (en) | Catalyst and method for synthesizing various trisubstituted olefin compounds and heterocyclic compounds | |
| Bang et al. | Sonochemical Reformatsky reaction using indium | |
| Mojtahedi et al. | Efficient solvent-free aminolysis of epoxides and oxetanes under MgBr2· OEt2 catalysis | |
| CN111362795B (en) | Preparation method of substituted butyrate derivatives | |
| CN115403459B (en) | Preparation method of 1, 4-dicarbonyl compound | |
| CN114773285A (en) | Efficient preparation method of alpha-amino oxazoline compound | |
| CN110452151B (en) | Synthetic method of alpha-indole glycine derivative | |
| JP7234145B2 (en) | Production of trimethylbenzene derivatives | |
| CN109574873B (en) | Dehydroabietic acid-based fluorescent compound and preparation method thereof | |
| CN113387886A (en) | 2-aminodibenzo [ c, e ] azepine compound and synthetic method thereof | |
| Akar et al. | Synthesis of meso‐tetra acid and ester functionalized calix [4] pyrroles | |
| CN111675654A (en) | Method for synthesizing tetrahydroquinoline compound by taking inert cyclopropane as raw material | |
| CN114478152B (en) | Synthesis method of perfluoroalkane compound and derivative thereof | |
| Zhu et al. | Reactions of fluoroalkanesulfonyl azides with cyclic vinyl ethers | |
| CN115490613B (en) | Preparation method of aromatic nitrile compound | |
| CN115197124B (en) | Method for synthesizing polysubstituted pyridine derivative based on alpha, beta-unsaturated oxime ester under catalysis of ammonium iodide | |
| CN110498757B (en) | Synthesis method of metal-free 3-acyl indole compound | |
| CN115057808B (en) | Synthesis method of Z-3-vinyl substituted isoindolinone compound | |
| CN116768745A (en) | Synthesis method of photoinduction N-aryl benzamide 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 |