CN111187266B - Method for regioselective dearomatization of compound containing indole skeleton - Google Patents
Method for regioselective dearomatization of compound containing indole skeleton Download PDFInfo
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- CN111187266B CN111187266B CN202010068700.XA CN202010068700A CN111187266B CN 111187266 B CN111187266 B CN 111187266B CN 202010068700 A CN202010068700 A CN 202010068700A CN 111187266 B CN111187266 B CN 111187266B
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 23
- 238000000034 method Methods 0.000 title claims abstract description 19
- 125000001041 indolyl group Chemical group 0.000 title claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- 239000002904 solvent Substances 0.000 claims abstract description 9
- 239000000758 substrate Substances 0.000 claims abstract description 9
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- -1 aldehyde compound Chemical class 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical compound COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 230000007935 neutral effect Effects 0.000 claims description 4
- 238000006276 transfer reaction Methods 0.000 claims description 2
- 150000002475 indoles Chemical class 0.000 abstract description 7
- 125000000168 pyrrolyl group Chemical group 0.000 abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 96
- 239000000047 product Substances 0.000 description 20
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 16
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- 239000000126 substance Substances 0.000 description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
- UEOHATPGKDSULR-UHFFFAOYSA-N 9h-carbazol-4-ol Chemical compound N1C2=CC=CC=C2C2=C1C=CC=C2O UEOHATPGKDSULR-UHFFFAOYSA-N 0.000 description 4
- 239000000370 acceptor Substances 0.000 description 4
- 125000002837 carbocyclic group Chemical group 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000005899 aromatization reaction Methods 0.000 description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 238000010499 C–H functionalization reaction Methods 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 238000003547 Friedel-Crafts alkylation reaction Methods 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 230000006324 decarbonylation Effects 0.000 description 1
- 238000006606 decarbonylation reaction Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/20—Spiro-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for regioselective dearomatization of a compound containing an indole skeleton by substrate regulation, belonging to the technical field of chemical synthesis. The method can be used for carrying out the reaction under the condition that hexafluoroisopropanol is used as a solvent and the temperature is 25 ℃. The method realizes the dearomatization of the benzene ring of the indole skeleton for the first time, and realizes the respective dearomatization of the benzene ring and the pyrrole ring of the indole compounds by adjusting the difference of substrates. The method is novel and convenient, simple to operate, wide in substrate applicability and high in atom economy.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for regioselective dearomatization of a compound containing an indole skeleton.
Background
Indoles and indole derivatives are a very specific class of heterocyclic compounds that are widely found in many natural products and pharmaceutical compounds. Therefore, the modification of the indole skeleton has been intensively studied over the past decades. However, various proposed synthetic methods are directed to the more nucleophilic pyrrole moiety in the indole nucleus, and the functionalization of the indole backbone in the carbon ring has not yet been developed. Dearomatization is a unique strategy for functionalizing planar aromatic compounds, and provides an intuitive and practical method for synthesizing various valuable three-dimensional molecules. In recent years, dearomatization of indoles has made great progress in the synthesis of various indoles and indole-based compounds (acc. chem. res.,2014,47, 2558; chem. eur. j.,2016,22, 2856). However, at present, there is no example of dearomatization of the carbocyclic indole skeleton. Therefore, it is very necessary to develop a strategy to achieve carbocyclic dearomatization of the indole backbone from readily available substrates to construct a more useful backbone.
Redox neutral C-H functionalization reactions involving the process of hydrogen migration are ideal for the synthesis of many versatile and more complex molecules due to their inherent high efficiency and high atom economy. Over the past few years, many hydrogen acceptors have been reported for hydrogen transport. However, in almost all cases, hydride acceptors must be prepared in advance by lengthy steps (chem. commun.,2018,54, 7928; org. lett.,2017,19, 1566; org. lett.,2017,19, 1334).
Aromatization is an important thermodynamic driving force for various synthetic transformations. The o-phenyleneinone compounds (o-QMs) having a strong aromatization tendency have been widely studied as a nucleophile, a cycloaddition reagent and a synthetic intermediate of an oxa-6 π electrocyclic reaction. The guide group is widely applied to direct C-H bond functionalization reaction catalyzed by transition metal. Hydroxyl genes enjoy their full name for their in situ activation/targeting capabilities in a variety of catalytic systems. To address the problem of dearomatization of the indole backbone in the carbocyclic ring, the present invention contemplates the introduction of an activated/targeted hydroxyl group in the carbocyclic ring to reverse the conventional reaction site in the pyrrole ring.
Disclosure of Invention
The invention provides a method for regioselective dearomatization of a compound containing an indole skeleton, which adopts the following technical scheme:
the selective dearomatization of indole skeleton region is realized by taking a compound (I) and an anthranilic aldehyde compound as reaction substrates through redox neutral hydrogen transfer reaction in a solvent;
the compound (I) is 4-hydroxy carbazole or ethyl (1H-indole-4-acyl) carbonate;
preferably, the compound (I) and the anthranilic aldehyde compound are used in a molar ratio of 1: 1.
On the basis of the scheme, the reaction solvent is hexafluoroisopropanol, and the reaction is carried out at room temperature.
On the basis of the scheme, the structural formula of the anthranilic aldehyde compound is as follows:
wherein,
n is 1 or 3;
R1is any one of hydrogen, methyl, methoxy, fluorine, trifluoromethyl and halogen.
On the basis of the scheme, the specific reaction steps are as follows:
taking 0.1mmol of the compound (I) and 0.1mmol of anthranilic aldehyde compound respectively, adding 2mL of hexafluoroisopropanol as a solvent, and reacting for 8h at room temperature; detecting the reaction by thin-layer chromatography, and carrying out column chromatography to obtain the product.
In the above technical scheme, when the compound (i) is 4-hydroxy carbazole, the chemical reaction formula is as follows:
wherein,
n is 1 or 3;
R1is any one of hydrogen, methyl, methoxy, fluorine, trifluoromethyl and halogen;
the dotted line represents the spatial structure of the compound;
the reaction mechanism is as follows: firstly, HFIP aggregates on 4-hydroxycarbazole 4 and benzaldehyde 1, mediating friedel-crafts alkylation/dehydration/hydrogen migration/cyclization processes; thereby providing the final product 5.
Based on the above scheme, when compound (I) is ethyl (1H-indole-4-acyl) carbonate, the chemical reaction formula is as follows:
wherein,
n is 1 or 3;
R1is any one of hydrogen, methyl, methoxy, fluorine, trifluoromethyl and halogen;
the dotted line represents the spatial structure of the compound;
the reaction mechanism is as follows: first, the carbonyl group of 1 is activated by hydrogen bonding clustering of HFIP, promoting friedel-crafts reaction with indole 6 to give intermediate a. Intermediate a is then dehydrated under the promotion of HFIP to form intermediate B. Next, the electron deficient olefin acts as a hydrogen acceptor, initiating hydrogen transfer to yield intermediate C, accompanied by a decarbonylation process. Subsequently, intramolecular cyclization gave product 7.
The invention has the beneficial effects that:
the invention discloses a method for regioselective dearomatization of a compound containing an indole skeleton by substrate regulation. The method can be used for carrying out the reaction under the condition that hexafluoroisopropanol is used as a solvent and the temperature is 25 ℃. The method realizes the dearomatization of the benzene ring of the indole skeleton for the first time, and realizes the respective dearomatization of the benzene ring and the pyrrole ring of the indole compounds by adjusting the difference of substrates. The method is novel and convenient, simple to operate, wide in substrate applicability and high in atom economy.
The present invention aims to build a redox neutral strategy to assemble more complex molecules in one step, which solves the huge challenges in hydrogen transfer and indole chemistry, with the following advantages: (1) hydrogen migration is initiated by the recovered aromatization driving force of in-situ generation of o-QMs without the need of preparing a hydrogen acceptor in advance; (2) selective dearomatization of the indole skeleton in the carbocyclic and pyrrole rings.
Detailed Description
Terms used in the present invention have generally meanings as commonly understood by one of ordinary skill in the art, unless otherwise specified.
The present invention will be described in further detail with reference to the following data in conjunction with specific examples. The following examples are intended to illustrate the invention and are not intended to limit the scope of the invention in any way.
Reaction conditions for the products described in examples 1-9: taking 0.1mmol of each of 4-hydroxy carbazole and anthranilic aldehyde compounds, adding 2mL of hexafluoroisopropanol as a solvent, and reacting for 8h at room temperature; TLC detection, decompression drying after the material consumption (about 8 hr), silica gel column chromatographic separation, eluting petroleum ether: ethyl acetate was 3: 1. The reaction formula is as follows:
example 1
The chemical formula of the product is as follows: c23H21N2O
Molecular weight: 341.16
Structural formula (xvi):
yield: 73 percent
1H NMR(500MHz,DMSO)δ12.13(s,1H),8.04(d,J=7.0Hz,1H),7.49(d,J=7.3Hz,1H),7.32–7.17(m,2H),7.09(t,J=7.5Hz,1H),7.03(d,J=7.0Hz,1H),6.93(d,J=9.9Hz,1H),6.55(t,J=8.8Hz,2H),5.99(d,J=9.9Hz,1H),3.79(dd,J=9.2,6.0Hz,1H),3.49(t,J=7.7Hz,1H),3.31(s,1H),3.12(d,J=8.2Hz,1H),2.61(d,J=15.8Hz,1H),1.97–1.78(m,2H),1.78–1.63(m,1H),1.19(d,J=10.2Hz,1H);13C NMR(126MHz,DMSO)δ194.9,146.9,143.2,140.5,137.3,129.3,127.9,124.5,124.0,123.0,120.9,119.6,118.1,115.5,112.7,111.0,110.7,64.7,48.7,47.5,40.5,40.4,40.3,40.3,40.2,40.1,39.9,39.8,39.7,39.5,39.1,27.7,23.5.
Example 2
The chemical formula of the product is as follows: c24H23N2O
Molecular weight: 355.18
Structural formula (xvi):
yield: 60 percent of
1H NMR(500MHz,DMSO)δ12.12(s,1H),8.04(d,J=6.8Hz,1H),7.50(d,J=8.2Hz,1H),7.30–7.19(m,2H),6.96–6.90(m,2H),6.38(d,J=9.5Hz,2H),6.00(d,J=9.9Hz,1H),3.78(dd,J=9.6,5.9Hz,1H),3.49(t,J=7.7Hz,1H),3.28(d,J=15.6Hz,1H),3.12(dd,J=16.7,8.8Hz,1H),2.58(d,J=15.6Hz,1H),2.25(s,3H),1.87(dd,J=19.3,8.3Hz,2H),1.77–1.68(m,1H),1.21(dd,J=21.2,11.8Hz,1H);13C NMR(126MHz,DMSO)δ195.0,146.9,143.1,140.7,137.3,136.7,129.2,124.5,124.0,122.9,120.9,118.0,116.8,116.4,112.7,111.6,110.7,64.7,49.0,47.5,38.8,27.7,23.5,21.8.
Example 3
The chemical formula of the product is as follows: c24H20F3N2O
Molecular weight: 409.15
Structural formula (xvi):
yield: 82 percent of
1H NMR(500MHz,DMSO)δ12.17(s,1H),8.10–7.97(m,1H),7.51(d,J=7.2Hz,1H),7.32–7.19(m,3H),6.95(d,J=9.9Hz,1H),6.84(d,J=7.7Hz,1H),6.76(s,1H),5.96(d,J=9.9Hz,1H),3.84(dd,J=9.9,5.8Hz,1H),3.58(t,J=7.9Hz,1H),3.33(s,1H),3.17(dd,J=17.0,8.9Hz,1H),2.73(d,J=16.2Hz,1H),1.97–1.86(m,2H),1.75(dt,J=10.0,5.6Hz,1H),1.27–1.17(m,1H).;13C NMR(126MHz,DMSO)δ194.4,147.0,143.5,139.8,137.3,130.0,127.4(d,J=302.4Hz),124.5,124.2,124.1,123.1,120.9,118.5,112.8,111.3(q,J=3.8Hz),110.7,106.4(d,J=3.8Hz),64.7,47.9,47.5,38.8,27.6,23.5.
Example 4
The chemical formula of the product is as follows: c23H20ClN2O
Molecular weight: 375.13
Structural formula (xvi):
yield: 50 percent of
1H NMR(500MHz,DMSO)δ12.16(s,1H),8.04(d,J=7.4Hz,1H),7.50(d,J=7.7Hz,1H),7.31–7.21(m,2H),7.12(s,2H),6.95(d,J=9.9Hz,1H),6.60–6.53(m,1H),5.96(d,J=9.9Hz,1H),3.79(dd,J=9.6,5.9Hz,1H),3.50(t,J=8.1Hz,1H),3.29(d,J=16.0Hz,1H),3.12(dd,J=16.9,8.7Hz,1H),2.66(d,J=16.0Hz,1H),1.90(dd,J=16.7,9.0Hz,2H),1.74(dd,J=11.7,5.8Hz,1H),1.23–1.16(m,1H).;13C NMR(126MHz,DMSO)δ194.5,146.9,142.1,140.0,137.3,128.8,127.4,124.5,124.1,123.1,121.7,120.9,118.8,118.4,112.8,112.2,110.7,64.7,48.2,47.7,38.7,27.6,23.5.
Example 5
The chemical formula of the product is as follows: c24H23N2O2
Molecular weight: 371.18
Structural formula (xvi):
yield: 56 percent
1H NMR(500MHz,DMSO)δ12.09(s,1H),8.11(d,J=7.6Hz,1H),7.52(d,J=7.9Hz,1H),7.25(dt,J=23.9,7.2Hz,2H),7.11(t,J=8.1Hz,1H),6.40(d,J=10.3Hz,1H),6.38–6.26(m,3H),4.13–4.05(m,1H),3.70(d,J=13.0Hz,3H),3.50(t,J=7.5Hz,1H),3.33–3.21(m,2H),2.93(d,J=16.4Hz,1H),1.85(dd,J=19.2,8.6Hz,2H),1.58–1.49(m,1H),1.22(dd,J=20.0,9.8Hz,1H);13C NMR(126MHz,DMSO)δ182.0,157.7,153.7,144.3,143.5,137.1,132.1,128.4,124.3,123.6,122.1,121.0,112.3,112.1,106.3,105.2,99.3,63.5,55.7,48.0,39.0,34.1,27.8,23.3.
Example 6
The chemical formula of the product is as follows: c23H20FN2O
Molecular weight: 359.16
Structural formula (xvi):
yield: 67 percent
1H NMR(500MHz,DMSO)δ12.18(s,1H),8.05(d,J=6.9Hz,1H),7.51(d,J=7.4Hz,1H),7.31–7.23(m,2H),7.12(dd,J=15.3,7.9Hz,1H),6.97(d,J=9.9Hz,1H),6.41(dd,J=15.8,8.2Hz,2H),5.98(d,J=9.9Hz,1H),3.76(dd,J=9.6,5.9Hz,1H),3.52(t,J=7.6Hz,1H),3.16(dd,J=16.8,8.8Hz,1H),3.08(d,J=16.2Hz,1H),2.75(d,J=16.0Hz,1H),1.94–1.83(m,2H),1.75(dd,J=11.1,5.5Hz,1H),1.23(dd,J=19.8,10.1Hz,1H);13C NMR(126MHz,DMSO)δ194.5,161.3(d,J=239.4Hz),147.0,144.8(d,J=5.0Hz),139.8,137.3,128.5(d,J=11.3Hz),124.5,124.1,123.1,121.0,118.5,112.8,110.7,107.2,106.2(d,J=20.1Hz),102.0(d,J=22.4Hz),64.2,47.8,47.8,31.4,27.6,23.4.
Example 7
The chemical formula of the product is as follows: c23H20BrN2O
Molecular weight: 419.08
Structural formula (xvi):
yield: 65 percent of
1H NMR(500MHz,DMSO)δ12.20(s,1H),8.05(d,J=6.8Hz,1H),7.51(d,J=7.2Hz,1H),7.35–7.21(m,2H),7.05(t,J=7.9Hz,1H),6.98(d,J=9.8Hz,1H),6.85(d,J=7.7Hz,1H),6.61(d,J=8.0Hz,1H),6.00(d,J=9.8Hz,1H),3.81–3.73(m,1H),3.50(d,J=7.2Hz,1H),3.17(t,J=13.5Hz,2H),2.81(d,J=16.4Hz,1H),1.99–1.84(m,2H),1.80–1.71(m,1H),1.29–1.18(m,1H);13C NMR(126MHz,DMSO)δ194.2,147.0,144.8,139.9,137.3,129.1,125.1,124.5,124.1,123.1,120.9,119.1,118.6,112.8,110.7,110.6,64.2,55.4,48.8,47.7,27.6,23.6.
Example 8
The chemical formula of the product is as follows: c25H24FN2O
Molecular weight: 387.19
Structural formula (xvi):
yield: 85 percent of
1H NMR(500MHz,DMSO)δ12.16(s,1H),8.10–8.02(m,1H),7.51(d,J=7.4Hz,1H),7.31–7.21(m,2H),7.15–7.07(m,1H),6.97(d,J=9.9Hz,1H),6.67(d,J=8.4Hz,1H),6.49(t,J=8.8Hz,1H),6.24(d,J=9.9Hz,1H),3.53(t,J=10.3Hz,2H),3.39(dd,J=16.7,9.1Hz,1H),3.22(d,J=16.7Hz,1H),2.60(d,J=16.4Hz,1H),1.85–1.76(m,1H),1.70(d,J=5.4Hz,1H),1.63–1.50(m,3H),1.31(dd,J=14.3,7.4Hz,3H);13C NMR(126MHz,DMSO)δ195.2,161.3(d,J=240.6Hz),148.9(d,J=7.2Hz),147.0,140.8,137.3,127.8(d,J=10.1Hz),124.4,124.0,123.0,120.9,117.4,112.8,111.2,110.5,108.4(d,J=19.5Hz),103.3(d,J=22.0Hz),66.2,50.9,50.7,31.7,30.5,29.0,28.5,26.7.
Example 9
The chemical formula of the product is as follows: c25H24ClN2O
Molecular weight: 403.16
Structural formula (xvi):
yield: 78 percent of
1H NMR(500MHz,DMSO)δ12.18(s,1H),8.14–8.00(m,1H),7.51(d,J=7.2Hz,1H),7.30–7.22(m,2H),7.12(t,J=8.1Hz,1H),6.98(d,J=9.9Hz,1H),6.83(d,J=8.4Hz,1H),6.79(d,J=7.8Hz,1H),6.24(d,J=9.9Hz,1H),3.53(dd,J=15.3,6.4Hz,1H),3.47(dd,J=9.4,4.7Hz,1H),3.39(dd,J=20.1,10.8Hz,2H),3.26(d,J=17.0Hz,1H),2.66(d,J=17.0Hz,1H),1.85–1.78(m,1H),1.74–1.67(m,1H),1.64–1.57(m,2H),1.57–1.50(m,1H),1.34–1.25(m,3H);13C NMR(126MHz,DMSO)δ195.0,146.9,140.8,137.3,128.0,124.0,123.0,120.9,117.7,117.4,113.7,112.7,66.0,51.9,50.8,36.7,30.5,28.9,28.4,26.6.
Reaction conditions for the products described in examples 10-16: taking 0.1mmol of ethyl (1H-indole-4-acyl) carbonate and 0.1mmol of anthranilic aldehyde compound respectively, adding 2mL of hexafluoroisopropanol serving as a solvent, and reacting for 8H at room temperature; the reaction formula is as follows:
example 10
Product ofThe chemical formula is as follows: c19H19N2O
Molecular weight: 291.15
Structural formula (xvi):
yield: 64 percent
1H NMR(500MHz,DMSO)δ9.72(s,1H),7.77(s,1H),7.19(t,J=7.6Hz,1H),7.14–7.04(m,2H),7.02(d,J=7.0Hz,1H),6.75(d,J=8.0Hz,1H),6.57(d,J=6.8Hz,2H),4.45–4.31(m,1H),3.86(d,J=16.2Hz,1H),3.42(s,1H),3.27(q,J=7.9Hz,1H),2.45(d,J=16.2Hz,1H),1.86(s,2H),1.54(d,J=5.7Hz,1H),0.92–0.80(m,1H);13C NMR(126MHz,DMSO)δ175.4,157.2,154.1,144.2,129.5,128.7,127.9,125.1,119.7,115.8,114.4,112.7,111.4,59.4,58.0,47.5,32.4,27.7,23.2.
Example 11
The chemical formula of the product is as follows: c19H18ClN2O
Molecular weight: 325.11
Structural formula (xvi):
yield: 81 percent of
1H NMR(500MHz,DMSO)δ9.75(s,1H),7.76(s,1H),7.19(t,J=7.8Hz,1H),7.16–7.02(m,3H),6.75(d,J=8.1Hz,1H),6.55(d,J=8.6Hz,1H),4.37(dd,J=9.6,6.1Hz,1H),3.81(d,J=16.4Hz,1H),3.42(d,J=10.4Hz,1H),3.24(q,J=8.3Hz,1H),2.48(d,J=16.6Hz,1H),1.86(d,J=5.1Hz,2H),1.58–1.49(m,1H),0.91–0.80(m,1H);13C NMR(126MHz,DMSO)δ175.0,157.3,154.1,143.1,129.7,128.2,127.5,124.8,121.7,119.1,114.5,112.7,112.6,59.4,57.6,47.7,32.1,27.8,23.3.
Example 12
The chemical formula of the product is as follows: c19H18BrN2O
Molecular weight: 369.06
Structural formula (xvi):
yield: 62 percent of
1H NMR(500MHz,DMSO)δ9.75(s,1H),7.76(s,1H),7.26–7.17(m,3H),7.06(d,J=7.5Hz,1H),6.75(d,J=8.1Hz,1H),6.51(d,J=8.6Hz,1H),4.36(dd,J=9.8,6.0Hz,1H),3.81(d,J=16.4Hz,1H),3.42(td,J=9.0,3.5Hz,1H),3.23(q,J=8.5Hz,1H),2.48(d,J=16.8Hz,1H),1.91–1.82(m,2H),1.57–1.47(m,1H),0.91–0.81(m,1H);13C NMR(126MHz,DMSO)δ174.5,156.8,153.6,142.9,130.4,129.9,129.2,124.3,121.7,114.0,112.6,112.3,106.1,58.9,57.0,47.2,31.6,27.3,22.8.
Example 13
The chemical formula of the product is as follows: c19H18FN2O
Molecular weight: 309.14
Structural formula (xvi):
yield: 76 percent of
1H NMR(500MHz,DMSO)δ9.78(s,1H),7.80(s,1H),7.21(t,J=7.8Hz,1H),7.16–7.09(m,1H),7.07(d,J=7.5Hz,1H),6.76(d,J=8.1Hz,1H),6.42(t,J=8.5Hz,2H),4.33(dd,J=9.3,6.3Hz,1H),3.61(d,J=16.7Hz,1H),3.43(d,J=8.0Hz,1H),3.32–3.25(m,1H),2.55(s,1H),1.86(s,2H),1.59–1.50(m,1H),0.87(t,J=9.5Hz,1H);13C NMR(126MHz,DMSO)δ174.9,160.9(d,J=240.7Hz),159.9,157.3,154.2,145.9,145.8(d,J=8.8Hz),129.8,128.7(d,J=11.3Hz),124.7,114.5,112.8,107.5,106.3(d,J=20.3Hz),102.3(d,J=22.2Hz),58.9,57.2,47.8,27.7,25.1,23.2.
Example 14
The chemical formula of the product is as follows: c19H18ClN2O
Molecular weight: 325.11
Structural formula (xvi):
yield: 76 percent of
1H NMR(500MHz,DMSO)δ9.81(s,1H),7.82(s,1H),7.21(t,J=7.9Hz,1H),7.10(dd,J=17.9,7.9Hz,2H),6.78(d,J=8.1Hz,1H),6.68(d,J=7.8Hz,1H),6.55(d,J=8.2Hz,1H),4.33(dd,J=9.6,6.2Hz,1H),3.67(d,J=17.0Hz,1H),3.40(dt,J=10.5,7.2Hz,1H),3.31(dd,J=16.8,8.2Hz,1H),2.60(d,J=17.0Hz,1H),1.93–1.76(m,2H),1.62–1.49(m,1H),0.93–0.79(m,1H);13C NMR(126MHz,DMSO)δ175.0,157.3,154.2,145.7,133.4,129.9,128.8,124.6,117.1,116.2,114.6,112.8,110.4,58.8,57.9,47.7,30.2,27.7,23.3.
Example 15
The chemical formula of the product is as follows: c19H18BrN2O
Molecular weight: 369.06
Structural formula (xvi):
yield: 78 percent of
1H NMR(500MHz,DMSO)δ9.81(s,1H),7.83(s,1H),7.22(t,J=7.9Hz,1H),7.11–7.01(m,2H),6.85(d,J=7.8Hz,1H),6.77(d,J=8.1Hz,1H),6.60(d,J=8.2Hz,1H),4.33(dd,J=9.5,6.3Hz,1H),3.65(d,J=16.9Hz,1H),3.42(dd,J=11.9,8.7Hz,1H),3.34–3.28(m,1H),2.55(d,J=16.9Hz,1H),1.92–1.83(m,2H),1.57(dd,J=10.6,5.2Hz,1H),0.92–0.82(m,1H);13C NMR(126MHz,DMSO)δ174.8,157.1,154.0,145.7,129.7,129.1,124.4,124.3,119.1,118.4,114.4,112.6,110.8,58.7,58.0,47.5,33.0,27.5,23.2.
Example 16
The chemical formula of the product is as follows: c21H22BrN2O
Molecular weight: 396.08
Structural formula (xvi):
yield: 76 percent of
1H NMR(500MHz,DMSO)δ9.75(s,1H),7.92(s,1H),7.24–7.15(m,2H),7.11(d,J=2.2Hz,1H),7.05(d,J=7.4Hz,1H),6.71(dd,J=14.1,8.5Hz,2H),4.37–4.28(m,2H),3.76(d,J=16.3Hz,1H),3.40(t,J=4.8Hz,1H),2.35(d,J=16.4Hz,1H),1.72(dd,J=12.1,6.1Hz,1H),1.69–1.61(m,1H),1.41(ddd,J=24.7,13.6,5.4Hz,4H),1.31(d,J=8.6Hz,1H),0.94(dd,J=9.2,4.6Hz,1H);13C NMR(126MHz,DMSO)δ174.9,156.7,153.3,145.9,130.3,129.8,129.2,125.2,122.8,114.3,113.9,112.2,106.8,60.5,59.6,49.3,31.6,29.2,29.1,28.8,25.7.
The above-mentioned embodiments only provide several embodiments of the present invention, but should not be construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (3)
1. A method for regioselective dearomatization of a compound containing an indole skeleton is characterized in that a compound (I) and an anthranilic aldehyde compound are used as reaction substrates, and the regioselective dearomatization of the indole skeleton is realized through a redox neutral hydrogen transfer reaction in a solvent;
the compound (I) is ethyl (1H-indole-4-acyl) carbonate;
the structural formula of the anthranilic aldehyde compound is as follows:
wherein,
n=1;
R1is any one of hydrogen, methyl, methoxy, fluorine, trifluoromethyl and halogen;
the solvent is hexafluoroisopropanol;
the reaction temperature is room temperature;
the chemical reaction formula is as follows:
wherein,
n=1;
R1is any one of hydrogen, methyl, methoxy, fluorine, trifluoromethyl and halogen;
the dotted lines represent spatial structures.
2. The process for the regioselective dearomatization of compounds having an indole skeleton according to claim 1, characterized in that the compound (i) and the anthranilic aldehyde compound are used in a molar ratio of 1: 1.
3. The process for the selective dearomatization of a zone containing indole skeleton compounds according to any of claims 1 to 2, characterized by the steps of:
taking 0.1mmol of the compound (I) and 0.1mmol of anthranilic aldehyde compound respectively, adding 2mL of solvent, and reacting for 8h at room temperature.
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