CN115368292B - Benzondoles compound and synthesis method thereof - Google Patents

Benzondoles compound and synthesis method thereof Download PDF

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CN115368292B
CN115368292B CN202211058334.5A CN202211058334A CN115368292B CN 115368292 B CN115368292 B CN 115368292B CN 202211058334 A CN202211058334 A CN 202211058334A CN 115368292 B CN115368292 B CN 115368292B
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benzindole
vinylene carbonate
amino naphthalene
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CN115368292A (en
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南江
肖海燕
胡岩
任鑫
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Shaanxi University of Science and Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/58—[b]- or [c]-condensed
    • C07D209/60—Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/58—[b]- or [c]-condensed
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/58—[b]- or [c]-condensed
    • C07D209/70—[b]- or [c]-condensed containing carbocyclic rings other than six-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Abstract

The invention discloses a benzoindole compound and a synthesis method thereof. The invention provides a benzoindole compound which is obtained by taking vinylene carbonate as a synthon, taking the vinylene carbonate and a naphthylamine compound as raw materials, removing one molecule of carbon dioxide, carrying out a heterocyclic reaction and dehydrating. Compared with the traditional method for synthesizing the benzindole skeleton, the vinylene carbonate is a novel C2 synthon to participate in the synthesis of the benzindole, the method is simple to operate, does not need a ligand or a plurality of additives, has higher yield of target compounds, has high molecular utilization rate, and can synthesize by-product carbonic acid in the reaction of the additive lithium carbonate.

Description

Benzondoles compound and synthesis method thereof
Technical Field
The invention belongs to the technical field of organic technology, and relates to a benzindole compound and a synthesis method thereof.
Background
Benzoindoles are one of the important structures of nitrogen-containing heterocyclic compounds, and organic molecules containing such backbones have very wide application in the fields of pharmaceutical chemistry and materials, so that the search for efficient and economical synthesis methods of benzoindoles has been attracting attention. The vinylene carbonate compound is widely applied to synthesis of various carbocycles and heterocycles as an important synthon, and the metal-catalyzed direct cyclization of carbon-hydrogen bonds involved in the synthesis is a very efficient heterocyclic synthesis strategy [a)Afarinkia K,Bearpark M J,Ndibwami A,et al.An experimental and computational investigation of the Diels-Alder cycloadditions ofhalogen-substituted 2(H)-pyran-2ones[J].The Journal of Organic Chemistry,200570(4):1122-1133.b)Baran A,Günel A,Balci M.Synthesis ofbicyclo[2.2.2]octane-2578hexols(bishomoinositols)as glycosidase inhibitors[J].The Journal of Organic Chemistry,200873(12):4370-4375.c)Hara H,Hirano M,Tanaka K.A new route to substituted phenols bycationic rhodium(I)/BINAPcomplex-catalyzed decarboxylative[2+2+2]cycloaddition[J].Organic Letters 2009.11(6):1337-1340., a method for synthesizing benzindole by using vinylene carbonate as a coupling segment is not reported at present, but the method for synthesizing benzindole derivatives by using ethylene glycol as the coupling segment has harsh reaction conditions, needs to realize conversion at high temperature (190 ℃), has high reaction cost, and generates byproducts which are not friendly to the environment.
Disclosure of Invention
Aiming at the problems existing in the prior art, the invention provides the benzindole compound and the synthesis method thereof, which take the naphthylamine compound and the vinylene carbonate as reaction raw materials, efficiently synthesize the benzindole compound under milder reaction conditions in the presence of a solvent, have simple preparation process and low-cost and easily-obtained raw material sources, can neutralize byproducts in the reaction by using lithium carbonate, are environment-friendly, and reduce the reaction cost.
The invention is realized by the following technical scheme:
Adding a naphthylamine compound shown in a formula 1 and vinylene carbonate shown in a formula 2 into a solvent, reacting with ytterbium triflate serving as a catalyst and lithium carbonate serving as an additive under the protection of inert gas, and separating and purifying to obtain the benzindole compound shown in a formula 3;
Wherein R 1 is selected from hydrogen, halogen, alkyl, phenyl or substituted phenyl; r 2 is selected from alkyl, halogen, methoxy, heterocycle, phenyl or substituted phenyl, wherein the substituent in the substituted phenyl is nitro, tetramethylsilane, methylsulfonyl or trifluoromethyl.
Preferably, the specific preparation process for synthesizing the benzindole compound comprises the following steps: dissolving naphthylamine compound, vinylene carbonate, ytterbium triflate and lithium carbonate in a pressure-resistant pipe filled with solvent, inflating the pressure-resistant pipe for multiple times by using a balloon filled with helium until the air in the pressure-resistant pipe is completely emptied, heating and stirring the sealed pressure-resistant pipe, extracting by using dichloromethane and saturated sodium chloride aqueous solution after the reaction is complete, merging organic phases, drying by using anhydrous sodium sulfate and anhydrous calcium chloride, performing rotary evaporation concentration, and separating by using silica gel column chromatography to obtain the benzindole compound.
Preferably, the molar ratio of the naphthylamine compound to ytterbium triflate is 20:1-10:1; the molar ratio of the naphthylamine compound to the lithium carbonate is 10:1-5:1.
Preferably, the molar ratio of the naphthylamine compound to the vinylene carbonate is 10.0:1.0-1.0:2.0.
Preferably, the concentration of the vinylene carbonate in the solvent is 0.1-0.2 mol/l.
Preferably, the specific conditions of the reaction are: heating and stirring in an oil bath at 80-150 ℃ for 2-24 h.
Preferably, the solvent is one or a mixture of two of hexafluoroisopropanol, toluene and trifluoroacetic acid in any proportion.
Preferably, the naphthylamine compound includes one of 1-aminonaphthalene, 6-bromo-2-aminonaphthalene, 6-phenyl-2-aminonaphthalene, 7-methoxy-2-aminonaphthalene, 6-amino-2-naphthoic acid methyl ester, 4-chloro-1-aminonaphthalene, 5-bromo-1-aminonaphthalene, 4-fluoro-1-aminonaphthalene, 6-thiophene-2-aminonaphthalene, 1, 2-dihydronaphthalene-5-amine, 6-styryl-2-aminonaphthalene, 6-methyl-2-aminonaphthalene and 6-cyclopentyl-2-aminonaphthalene.
The benzindole compound is prepared by the synthesis method of the benzindole compound.
Preferably, the structural formula of the benzindole compound is as follows:
Wherein R 1 is selected from hydrogen, halogen, alkyl, phenyl or substituted phenyl; r 2 is selected from alkyl, halogen, methoxy, heterocycle, phenyl or substituted phenyl, wherein the substituent in the substituted phenyl is nitro, tetramethylsilane, methylsulfonyl or trifluoromethyl.
Compared with the prior art, the invention has the following beneficial technical effects:
The invention provides a benzindole compound and a synthesis method thereof, which are characterized in that a benzindole derivative is formed in one step by using a simple and easily available naphthylamine compound and vinylene carbonate as raw materials through a heterocyclization reaction under the catalysis of ytterbium metal, and an indole heterocycle is constructed. Compared with the traditional method for synthesizing the benzindole skeleton, the vinylene carbonate is a novel C2 synthon to participate in the synthesis of the benzindole, the method is simple to operate, does not need a ligand or a plurality of additives, has higher yield of target compounds, has high molecular utilization rate, and can neutralize by-product carbonic acid in the reaction by the additive lithium carbonate.
Furthermore, the synthetic method has the advantages of good universality of the reaction substrate, wide raw material sources, easy separation of target products under the optimized reaction condition, and potential application value in the fields of materials and medicines.
Drawings
FIG. 1 is a 1 H NMR spectrum of the product prepared in example 1;
FIG. 2 is a 13 C NMR spectrum of the product prepared in example 1;
FIG. 3 is a 1 H NMR spectrum of the product prepared in example 2;
FIG. 4 is a 13 C NMR spectrum of the product prepared in example 2;
FIG. 5 is a 1 H NMR spectrum of the product prepared in example 3;
FIG. 6 is a 13 C NMR spectrum of the product prepared in example 3;
FIG. 7 is a 1 H NMR spectrum of the product prepared in example 4;
FIG. 8 is a 13 C NMR spectrum of the product prepared in example 4;
FIG. 9 is a 1 H NMR spectrum of the product prepared in example 5;
FIG. 10 is a 13 C NMR spectrum of the product prepared in example 5;
FIG. 11 is a 1 H NMR spectrum of the product prepared in example 6;
FIG. 12 is a 13 C NMR spectrum of the product prepared in example 6;
FIG. 13 is a 1 H NMR spectrum of the product prepared in example 7;
FIG. 14 is a 13 C NMR spectrum of the product prepared in example 7;
FIG. 15 is a 1 H NMR spectrum of the product prepared in example 8;
FIG. 16 is a 13 C NMR spectrum of the product prepared in example 8;
FIG. 17 is a 1 H NMR spectrum of the product prepared in example 9;
FIG. 18 is a 13 C NMR spectrum of the product prepared in example 9;
FIG. 19 is a 1 H NMR spectrum of the product prepared in example 10;
FIG. 20 is a 13 C NMR spectrum of the product prepared in example 10;
FIG. 21 is a 1 H NMR spectrum of the product prepared in example 11;
FIG. 22 is a 13 C NMR spectrum of the product prepared in example 11;
FIG. 23 is a 1 H NMR spectrum of the product prepared in example 12;
FIG. 24 is a 13 C NMR spectrum of the product prepared in example 12;
FIG. 25 is a 1 H NMR spectrum of the product prepared in example 13;
FIG. 26 is a 13 C NMR spectrum of the product prepared in example 13;
FIG. 27 is a 1 H NMR spectrum of the product prepared in example 14;
FIG. 28 is a 13 C NMR spectrum of the product prepared in example 14;
FIG. 29 is a 1 H NMR spectrum of the product prepared in example 15;
FIG. 30 is a 13 C NMR spectrum of the product prepared in example 15.
Detailed Description
The invention will now be described in further detail with reference to specific examples, which are intended to illustrate, but not to limit, the invention.
The present application will be described in detail with reference to examples. It should be noted that, without conflict, the embodiments of the present application and features of the embodiments may be combined with each other.
Embodiments of the invention are described in further detail below:
A synthesis method of benzindole compound comprises adding naphthylamine compound shown in formula 1 and vinylene carbonate shown in formula 2 into solvent, wherein the molar ratio of naphthylamine compound to vinylene carbonate is 10.0:1.0-1.0:2.0, adding naphthylamine compound and vinylene carbonate into solvent, the concentration of vinylene carbonate in the solvent is 0.1-0.2 mol/L, and then the benzoindole compound shown in the formula 3 is obtained after heating and stirring for 2-24 hours in an oil bath kettle at 80-150 ℃ under the protection of inert gas helium.
Wherein R 1 is selected from hydrogen, halogen, alkyl, phenyl or substituted phenyl; r 2 is selected from alkyl, halogen, methoxy, heterocycle, phenyl or substituted phenyl, wherein the substituent in the substituted phenyl is nitro, tetramethylsilane, methylsulfonyl or trifluoromethyl.
The solvent is one or a mixture of two of hexafluoroisopropanol, toluene and trifluoroacetic acid in any proportion.
The invention is described in further detail below with reference to examples:
Example 1
Preparation of 1H-Benzo [ g ] indole
0.2Mmol of 1-aminonaphthalene, 0.3mmol of vinylene carbonate, 0.01mmol of ytterbium triflate as a catalyst and 0.02mmol of lithium carbonate as an additive are dissolved in a pressure-resistant tube (equipped with a magnetic stirrer) filled with 1.6mL of toluene, helium is filled with a balloon at least 3 times until the air is completely emptied, 15mL of the closed pressure-resistant tube is placed in an oil bath at 120 ℃ and heated and stirred for 12h, 30mL of dichloromethane and saturated aqueous sodium chloride solution are used for extraction three times after the reaction is completed, the organic phases are combined, dried with anhydrous sodium sulfate and anhydrous calcium chloride and concentrated by spin distillation, 25.7mg of solid compound is obtained by chromatography on a silica gel column, the yield is 77%, and the obtained product has the following structural formula:
As shown in fig. 1 and 2, the nuclear magnetism of the product is characterized ：1H NMR(400MHz,CDCl3):δ8.85(s,1H),8.04–7.96(m,2H),7.80(d,J＝8.6Hz,1H),7.61–7.48(m,3H),7.29(t,J＝2.6Hz,1H),6.77(t,J＝2.1Hz,1H).13C NMR(100MHz,CDCl3):δ130.4,128.9,125.5,123.9,123.8,122.3,121.8,120.8,120.8,119.4,104.3.
In this example, the naphthylamine compound and vinylene carbonate may be weighed in a molar ratio of 1.0:2.0.
Example 2
Preparation of 7-Bromo-3H-benzoe indole
0.5Mmol of 6-bromo-2-aminonaphthalene, 0.05mmol of vinylene carbonate, 0.05mmol of ytterbium triflate as a catalyst and 0.01mmol of lithium carbonate as an additive are dissolved in a pressure-resistant tube (equipped with a magnetic stirrer) filled with 1.6mL of hexafluoroisopropanol, helium is filled with a balloon at least 3 times until the air is completely emptied, 15mL of the closed pressure-resistant tube is placed in an oil bath at 150 ℃ and heated and stirred for 10 hours, after the reaction is completed, three extractions are carried out with 30mL of dichloromethane and saturated aqueous sodium chloride, the organic phases are combined, dried with anhydrous sodium sulfate and anhydrous calcium chloride and concentrated by spin distillation, 37.71mg of solid compound is obtained by chromatography on a silica gel column, the yield is 76%, and the obtained product has the following structural formula:
As shown in fig. 3 and 4, the nuclear magnetic characterization of the product ：1H NMR(400MHz,CDCl3):δ8.39(s,1H),8.34(d,J＝8.2Hz,1H),8.00(d,J＝8.1Hz,1H),7.71–7.62(m,2H),7.58–7.48(m,2H),7.28(t,J＝2.8Hz,1H),7.17(t,J＝2.6Hz,1H).13C NMR(100MHz,CDCl3):δ132.2,129.2,128.6,128.3,125.9,123.4,123.1,123.0,122.8,122.3,112.8,101.9.
In this example, the naphthylamine compound and vinylene carbonate can be weighed in a molar ratio of 10.0:1.0.
Example 3
Preparation of 7-Phenyl-3H-benzoe indole
0.2Mmol of 2-aminonaphthalene, 0.4mmol of vinylene carbonate, 0.01mmol of ytterbium triflate as a catalyst and 0.02mmol of lithium carbonate as an additive are dissolved in a pressure-resistant tube containing 2.0mL of toluene (equipped with a magnetic stirrer), helium is filled with a balloon at least 3 times until the air is completely emptied, 15mL of the closed pressure-resistant tube is placed in an oil bath at 80 ℃ and heated and stirred for 24h, after the reaction is completed, three times of extraction are carried out with 50mL of dichloromethane and saturated aqueous sodium chloride, the organic phases are combined, dried with anhydrous sodium sulfate and anhydrous calcium chloride and concentrated by spin distillation, 25.39mg of a yellow oily compound is obtained by chromatography on a silica gel column, the yield is 75%, and the obtained product has the following structural formula:
As shown in FIG. 5 and FIG. 6, the nuclear magnetic characterization of the product ：1H NMR(400MHz,CDCl3):δ8.39(s,1H),8.34(d,J＝8.2Hz,1H),8.00(d,J＝8.1Hz,1H),7.71–7.62(m,2H),7.58–7.48(m,2H),7.28(t,J＝2.8Hz,1H),7.17(t,J＝2.6Hz,1H).13C NMR(100MHz,CDCl3):δ132.2,129.2,128.6,128.3,125.9,123.4,123.1,123.0,122.8,122.3,112.8,101.9.
The concentration of vinylene carbonate in the solvent in this example may be 0.1 mole/liter.
Example 4
Preparation of 6-Phenyl-3H-benzoe indole
0.2Mmol of 6-phenyl-2-aminonaphthalene, 0.02mmol of vinylene carbonate, 0.05mmol of ytterbium triflate as a catalyst and 0.03mmol of lithium carbonate as an additive are dissolved in a pressure-resistant tube (equipped with a magnetic stirrer) containing 1.6mL of toluene, helium is filled with a balloon at least 3 times until the air is completely emptied, 15mL of the closed pressure-resistant tube is placed in an oil bath at 150 ℃ and heated and stirred for 2h, after the reaction is completed, three times are extracted with 40mL of dichloromethane and saturated aqueous sodium chloride solution, the organic phases are combined, dried with anhydrous sodium sulfate and anhydrous calcium chloride and concentrated by distillation, and 33.86mg of yellow oily compound is obtained by chromatography on a silica gel column, the obtained product has the following structural formula:
As shown in FIG. 7 and FIG. 8, the product nuclear magnetism is characterized ：.1H NMR(400MHz,CDCl3):δ8.45(s,1H),8.40(d,J＝8.5Hz,1H),8.22(s,1H),7.92(d,J＝8.4Hz,1H),7.87–7.82(m,2H),7.74(d,J＝8.8Hz,1H),7.62–7.54(m,3H),7.49–7.43(m,1H),7.32(t,J＝2.8Hz,1H),7.19(t,J＝2.2Hz,1H).13C NMR(100MHz,CDCl3):δ141.7,136.2,132.4,129.5,128.9,127.4,127.4,127.0,126.7,125.3,123.6,123.4,122.7,122.5,113.3,102.1.
The concentration of vinylene carbonate in the solvent in this example may be 0.2 mole/liter.
Example 5
Preparation of 8-Methoxy-3H-benzoe indole
0.4Mmol of 7-methoxy-2-aminonaphthalene, 0.3mmol of vinylene carbonate, 0.02mmol of ytterbium triflate as a catalyst and 0.03mmol of lithium carbonate as an additive are dissolved in a pressure-resistant tube (equipped with a magnetic stirrer) containing 1.6mL of toluene, helium is filled with a balloon at least 3 times until the air is completely emptied, 15mL of the closed pressure-resistant tube is placed in an oil bath at 120 ℃ and heated and stirred for 12h, after the reaction is completed, three times are extracted with 30mL of dichloromethane and saturated aqueous sodium chloride solution, the organic phases are combined, dried with anhydrous sodium sulfate and anhydrous calcium chloride and concentrated by distillation, and 27.10mg of yellow oily compound is obtained by chromatography on a silica gel column, the yield is 68%, and the obtained product has the following structural formula:
As shown in FIG. 9 and FIG. 10, the product nuclear magnetic characterization ：1H NMR(400MHz,CDCl3):δ8.46(s,1H),7.86(d,J＝8.9Hz,1H),7.64–7.56(m,2H),7.43(d,J＝8.8Hz,1H),7.31–7.28(m,1H),7.16–7.07(m,2H),4.05(s,3H).13C NMR(100MHz,CDCl3):δ158.0,132.7,130.1,129.4,124.1,122.9,122.3,121.9,114.7,110.4,102.8,101.8,55.4.
Example 6
Preparation of Methyl 3H-benzoe indole-7-carboxylate
0.2Mmol of methyl 6-amino-2-naphthoate, 0.3mmol of vinylene carbonate, 0.01mmol of ytterbium triflate as a catalyst and 0.02mmol of lithium carbonate as an additive are dissolved in a pressure-resistant tube (equipped with a magnetic stirrer) filled with 1.0mL of trifluoroacetic acid, helium is filled with a balloon for at least 3 times until the air is completely emptied, 15mL of the closed pressure-resistant tube is placed in an oil bath at 90 ℃ and heated and stirred for 15 hours, after the reaction is completed, three times of extraction are carried out with 30mL of dichloromethane and saturated sodium chloride aqueous solution, the organic phases are combined, dried with anhydrous sodium sulfate and anhydrous calcium chloride and concentrated by spin distillation, 30.45mg of yellow oily compound is obtained by chromatography on a silica gel column, the yield is 67%, and the obtained product has the following structural formula:
As shown in FIGS. 11 and 12, the product nuclear magnetic characterization ：1H NMR(400MHz,CDCl3):δ8.77–8.65(m,2H),8.32(d,J＝8.5Hz,1H),8.21(d,J＝8.5Hz,1H),7.74(d,J＝8.8Hz,1H),7.63(d,J＝8.8Hz,1H),7.36(t,J＝2.8Hz,1H),7.18(t,J＝2.8Hz,1H),4.04(s,3H).13C NMR(100MHz,CDCl3):δ167.8,133.5,131.7,130.9,128.3,125.6,124.8,124.1,123.2,122.9,122.6,113.7,102.5,52.1.
The conditions of heating and stirring in the oil bath in this example may be 150℃for 2 hours.
Example 7
Preparation of 5-Chloro-1H-benzog indole
0.3Mmol of 4-chloro-1-aminonaphthalene, 0.3mmol of vinylene carbonate, 0.01mmol of ytterbium triflate as a catalyst and 0.02mmol of lithium carbonate as an additive are dissolved in a pressure-resistant tube (equipped with a magnetic stirrer) filled with 2.0mL of toluene, helium is filled with a balloon at least 3 times until the air is completely emptied, 15mL of the closed pressure-resistant tube is placed in an oil bath at 120 ℃ and heated and stirred for 12h, after the reaction is completed, three times of extraction are carried out with 30mL of dichloromethane and saturated aqueous sodium chloride solution, the organic phases are combined, dried with anhydrous sodium sulfate and anhydrous calcium chloride and concentrated by distillation, 29.8mg of yellow solid compound is obtained by chromatography on a silica gel column, the obtained product has the following structural formula:
as shown in fig. 13 and 14, the conditions of heating and stirring in the oil bath in this example of the product nuclear magnetic characterization 1H NMR(400MHz,CDCl3):δ8.87(s,1H),8.41(d,J＝7.7Hz,1H),7.98(d,J＝7.12hz,1H),7.89(s,1H),7.65–7.54(m,2H),7.27(t,J＝2.7Hz,1H),6.69(t,J＝3.0Hz,1H).13C NMR(100MHz,CDCl3):δ129.5,127.2,126.3,125.9,124.8,124.1,123.5,123.0,122.4,120.9,119.7,104.1. may be 80 ℃ for 24 hours.
Example 8
Preparation of 6-Bromo-1H-benzog indole
0.2Mmol of 5-bromo-1-aminonaphthalene, 0.3mmol of vinylene carbonate, 0.01mmol of ytterbium triflate as a catalyst and 0.02mmol of lithium carbonate as an additive are dissolved in a pressure-resistant tube (equipped with a magnetic stirrer) containing 1.6mL of toluene, helium is filled with a balloon at least 3 times until the air is completely emptied, 15mL of the closed pressure-resistant tube is placed in an oil bath at 110 ℃ and heated and stirred for 12h, after the reaction is completed, three times are extracted with 30mL of dichloromethane and saturated aqueous sodium chloride solution, the organic phases are combined, dried with anhydrous sodium sulfate and anhydrous calcium chloride and concentrated by distillation, and 36.9mg of yellow solid compound is obtained by silica gel column chromatography, the yield is 75%, and the obtained product has the following structural formula:
as shown in fig. 15 and 16, the product nuclear magnetic characterization ：1H NMR(400MHz,CDCl3):δ8.91(s,1H),8.04–7.95(m,2H),7.88(d,J＝8.9Hz,1H),7.79(d,J＝7.5Hz,1H),7.43–7.33(m,2H),6.78(t,J＝3.1Hz,1H).13C NMR(100MHz,CDCl3):δ130.3,128.8,128.1,125.7,124.5,124.1,123.3,122.9,122.3,119.7,119.1,104.4.
Example 9
Preparation of 5-Fluoro-1H-benzog indole
0.2Mmol of 4-fluoro-1-aminonaphthalene, 0.3mmol of vinylene carbonate, 0.01mmol of ytterbium triflate as a catalyst and 0.02mmol of lithium carbonate as an additive are dissolved in a pressure-resistant tube (equipped with a magnetic stirrer) containing 1.6mL of toluene, helium is filled into a balloon at least 3 times until the air is completely emptied, 15mL of the closed pressure-resistant tube is placed in an oil bath at 120 ℃ and heated and stirred for 12h, 30mL of dichloromethane and saturated aqueous sodium chloride solution are used for three times after the reaction is completed, the organic phases are combined, dried with anhydrous sodium sulfate and anhydrous calcium chloride and concentrated by distillation, 17.5mg of yellow solid compound is obtained by silica gel column chromatography, the yield is 47%, and the obtained product has the following structural formula:
as shown in fig. 17 and 18, the product nuclear magnetic characterization ：11H NMR(400MHz,CDCl3):δ8.88(s,1H),8.23(d,J＝8.12hz,1H),8.01(d,J＝8.2Hz,1H),7.63(t,J＝7.12hz,1H),7.54(t,J＝7.6Hz,1H),7.44(d,J＝11.1Hz,1H),7.32(t,J＝2.8Hz,1H),6.72(t,J＝2.5Hz,1H).13C NMR(100MHz,CDCl3):δ154.1(d,J＝240.1Hz),126.9,126.5,124.0,123.0,122.3(d,J＝10.6Hz),122.0(d,J＝5.9Hz),121.1(d,J＝19.6Hz),119.4,119.4,104.5(d,J＝4.5Hz),103.4(d,J＝22.4Hz).
Example 10
Preparation of 7- (Thiophen-2-yl) -3H-benzoe indole
0.2Mmol of 6-thiophene-2-aminonaphthalene, 0.3mmol of vinylene carbonate, 0.01mmol of ytterbium triflate as a catalyst and 0.02mmol of lithium carbonate as an additive are dissolved in a pressure-resistant tube (equipped with a magnetic stirrer) filled with 0.8mL of toluene and 1.0mL of trifluoroacetic acid, helium is filled with a balloon at least 3 times until the air is completely emptied, 15mL of the closed pressure-resistant tube is placed in an oil bath at 120 ℃ and heated and stirred for 12 hours, after the reaction is completed, the three times of extraction are carried out with 30mL of dichloromethane and saturated sodium chloride aqueous solution, the organic phases are combined, dried with anhydrous sodium sulfate and anhydrous calcium chloride and concentrated in a rotary manner, and 32.18mg of yellow solid compound is obtained by silica gel column chromatography, the yield is 63%, and the obtained product has the following structural formula:
As shown in FIG. 19 and FIG. 20, the product nuclear magnetic characterization ：1H NMR(400MHz,CDCl3):δ8.46(s,1H),8.33(d,J＝8.4Hz,1H),8.19(s,1H),7.89(d,J＝8.5Hz,1H),7.69(d,J＝8.8Hz,1H),7.62(d,J＝4.0Hz,2H),7.58(d,J＝8.6Hz,1H),7.52–7.47(m,1H),7.31(d,J＝2.7Hz,1H),7.16(t,J＝2.1Hz,1H).13C NMR(100MHz,CDCl3):δ142.8,132.3,130.9,129.4,127.3,126.6,126.2,125.8,124.8,123.6,123.2,122.8,122.4,119.8,113.3,102.0.
Example 11
Preparation of 1H-Dibenzo [ e, g ] indole
0.2Mmol of 9-phenanthrylamine, 0.3mmol of vinylene carbonate, 0.01mmol of ytterbium triflate as a catalyst and 0.02mmol of lithium carbonate as an additive are dissolved in a pressure-resistant tube (equipped with a magnetic stirrer) filled with 0.8mL of toluene and 1.0mL of hexafluoroisopropanol, helium is filled into a balloon for at least 3 times until the air is completely emptied, 15mL of the sealed pressure-resistant tube is placed in an oil bath at 120 ℃ for heating and stirring for 12 hours, after the reaction is completed, 30mL of dichloromethane and saturated sodium chloride aqueous solution are used for three times, the organic phases are combined, the organic phases are concentrated by spin evaporation after being dried with anhydrous sodium sulfate and anhydrous calcium chloride, 31.72mg of light yellow solid compound is obtained by chromatography on silica gel, the yield is 73%, and the obtained product has the following structural formula:
As shown in fig. 21 and 22, the solvent for the reaction in this example of product nuclear magnetic characterization ：1H NMR(400MHz,CDCl3):δ8.76(s,1H),8.73–8.63(m,2H),8.24(d,J＝7.9Hz,1H),7.86–7.79(m,1H),7.63(t,J＝7.5Hz,1H),7.58–7.50(m,3H),7.18–7.02(m,2H).13C NMR(100MHz,CDCl3):δ128.7,128.4,128.3,127.1,126.9,126.6,124.7,124.2,124.0,123.5,123.5,123.2,121.6,120.7,119.7,103.1. may be hexafluoroisopropanol or a mixture of hexafluoroisopropanol and trifluoroacetic acid in any ratio.
Example 12
Preparation of 5,9-Dihydro-4H-indeno [1,7-fg ] indole
0.2Mmol of 1, 2-dihydronaphthalene-5-amine, 0.3mmol of vinylene carbonate, 0.01mmol of ytterbium triflate as a catalyst and 0.02mmol of lithium carbonate as an additive are dissolved in a pressure-resistant tube (equipped with a magnetic stirrer) filled with 0.8mL of trifluoroacetic acid and 0.8mL of hexafluoroisopropanol, helium is filled with a balloon for at least 3 times until the air is completely emptied, the 15mL of closed pressure-resistant tube is placed in an oil bath at 120 ℃ for heating and stirring for 12 hours, after the reaction is completed, the three times of extraction are carried out with 60mL of dichloromethane and saturated sodium chloride aqueous solution, the organic phases are combined, dried with anhydrous sodium sulfate and anhydrous calcium chloride, and then concentrated by spin, 29.76mg of pale yellow solid compound is obtained by silica gel column chromatography, the yield is 77%, and the obtained product has the following structural formula:
as shown in FIG. 23 and FIG. 24, the product nuclear magnetic characterization ：1H NMR(400MHz,CDCl3):δ8.74(s,1H),7.70(d,J＝8.1Hz,1H),7.57–7.49(m,2H),7.32(d,J＝7.0Hz,1H),7.26(t,J＝2.8Hz,1H),6.71(t,J＝3.0,2.2Hz,1H),3.57–3.38(m,4H).13C NMR(100MHz,CDCl3):δ146.4,138.0,136.7,127.9,127.2,126.5,122.1,119.8,118.0,115.2,113.3,104.2,31.3,29.3.
Example 13
(E) Preparation of 7-Styryl-3H-benzoe indole
0.2Mmol of 6-styryl-2-aminonaphthalene, 0.3mmol of vinylene carbonate, 0.01mmol of ytterbium triflate as a catalyst and 0.02mmol of lithium carbonate as an additive are dissolved in a pressure-resistant tube (equipped with a magnetic stirrer) filled with 1.6mL of toluene, helium is filled with a balloon at least 3 times until the air is completely emptied, 15mL of the sealed pressure-resistant tube is placed in an oil bath at 120 ℃ and heated and stirred for 12 hours, 30mL of dichloromethane and saturated aqueous sodium chloride solution are used for three times after the reaction is completed, the organic phases are combined, dried with anhydrous sodium sulfate and anhydrous calcium chloride and concentrated in a rotary manner, and 35.28mg of light yellow solid compound is obtained through chromatography on a silica gel column, the obtained product has the following structural formula:
as shown in FIGS. 25 and 26, the nuclear magnetic characterization of the product ：1H NMR(400MHz,CDCl3):δ8.50(s,1H),8.29(d,J＝8.5Hz,1H),8.02(s,1H),7.88(d,J＝8.6Hz,1H),7.69–7.62(m,3H),7.59(d,J＝8.8Hz,1H),7.45(t,J＝7.5Hz,2H),7.38–7.25(m,4H),7.18–7.10(m,1H).13C NMR(100MHz,CDCl3):δ137.7,132.4,129.4,129.3,128.7,127.8,127.6,127.5,127.4,126.4,123.5,123.5,123.2,122.9,122.5,113.1,102.0.
Example 14
Preparation of 7-Methyl-3H-benzoe indole
0.2Mmol of 6-methyl-2-aminonaphthalene, 0.3mmol of vinylene carbonate, 0.01mmol of ytterbium triflate as a catalyst and 0.02mmol of lithium carbonate as an additive are dissolved in a pressure-resistant tube (equipped with a magnetic stirrer) filled with 1.6mL of toluene, helium is filled with a balloon at least 3 times until the air is completely emptied, 15mL of the closed pressure-resistant tube is placed in an oil bath at 120 ℃ and heated and stirred for 12h, after the reaction is completed, three times of extraction are carried out with 30mL of dichloromethane and saturated aqueous sodium chloride solution, the organic phases are combined, dried with anhydrous sodium sulfate and anhydrous calcium chloride and concentrated by distillation, 31.15mg of white solid compound is obtained by silica gel column chromatography, the yield is 85%, and the obtained product has the following structural formula:
As shown in fig. 27 and 28, the product nuclear magnetic characterization ：1H NMR(400MHz,CDCl3):δ8.42(s,1H),8.22(d,J＝8.12hz,1H),7.75(s,1H),7.62–7.51(m,2H),7.46(d,J＝8.12hz,1H),7.29(t,J＝2.8Hz,1H),7.13(t,J＝3.1Hz,1H),2.61(s,3H).13C NMR(100MHz,CDCl3):δ132.7,131.9,129.4,127.8,127.8,126.2,122.9,122.8,122.5,122.1,112.7,101.7,21.6.
Example 15
Preparation of 7- (Cyclopent-1-en-1-yl) -3H-benzoe indole
0.2Mmol of 6-cyclopentyl-2-aminonaphthalene, 0.3mmol of vinylene carbonate, 0.01mmol of ytterbium triflate as a catalyst and 0.02mmol of lithium carbonate as an additive are dissolved in a pressure-resistant tube (equipped with a magnetic stirrer) filled with 1.6mL of toluene, helium is filled with a balloon at least 3 times until the air is completely emptied, 15mL of the closed pressure-resistant tube is placed in an oil bath at 120 ℃ and heated and stirred for 12h, after the reaction is completed, three times are extracted with 30mL of dichloromethane and saturated aqueous sodium chloride solution, the organic phases are combined, dried with anhydrous sodium sulfate and anhydrous calcium chloride and concentrated by spin distillation, 30.60mg of a yellow oily compound is obtained by chromatography on a silica gel, the yield is 65%, and the obtained product has the following structural formula:
As shown in FIGS. 29 and 30, the product nuclear magnetic characterization ：1H NMR(400MHz,CDCl3):δ8.43(s,1H),8.23(d,J＝8.5Hz,1H),7.90(s,1H),7.83(d,J＝8.5Hz,1H),7.64(d,J＝8.9Hz,1H),7.54(d,J＝8.8Hz,1H),7.33–7.25(m,1H),7.15–7.10(m,1H),6.39–6.32(m,1H),3.01–2.86(m,2H),2.73–2.59(m,2H),2.20–2.07(m,2H).13C NMR(100MHz,CDCl3):δ142.7,132.3,131.9,129.2,127.2,125.4,125.1,124.0,123.3,123.0,122.8,122.3,112.9,101.9,33.5,33.3,23.4.
The following detailed description is of embodiments, and is intended to provide further details of the application. Unless defined otherwise, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments in accordance with the application.

Claims (7)

1. The synthesis method of the benzindole compound is characterized in that a naphthylamine compound shown in a formula 1 and vinylene carbonate shown in a formula 2 are added into a solvent, ytterbium triflate is used as a catalyst and lithium carbonate is used as an additive, and after the reaction is carried out under the protection of inert gas, the benzindole compound shown in a formula 3 is obtained through separation and purification;
The naphthylamine compound is one of 1-amino naphthalene, 6-bromo-2-amino naphthalene, 6-phenyl-2-amino naphthalene, 7-methoxy-2-amino naphthalene, 6-amino-2-naphthoic acid methyl ester, 4-chloro-1-amino naphthalene, 5-bromo-1-amino naphthalene, 4-fluoro-1-amino naphthalene, 6-thiophene-2-amino naphthalene, 1, 2-dihydro-5-amine, 6-styryl-2-amino naphthalene, 6-methyl-2-amino naphthalene and 6-cyclopentyl-2-amino naphthalene.
2. The method for synthesizing the benzindole compound according to claim 1, wherein the specific preparation process of the benzindole compound is as follows: dissolving naphthylamine compound, vinylene carbonate, ytterbium triflate and lithium carbonate in a pressure-resistant pipe filled with solvent, inflating the pressure-resistant pipe for multiple times by using a balloon filled with helium until the air in the pressure-resistant pipe is completely emptied, placing the closed pressure-resistant pipe in an oil bath kettle for heating and stirring, extracting by using dichloromethane and saturated sodium chloride aqueous solution after the reaction is completed, merging organic phases, drying by using anhydrous sodium sulfate and anhydrous calcium chloride, performing rotary evaporation concentration, and separating by using a silica gel column chromatography to obtain the benzindole compound.
3. The method for synthesizing the benzindole compound according to claim 1, wherein the molar ratio of the naphthylamine compound to ytterbium triflate is 20:1-10:1; the molar ratio of the naphthylamine compound to the lithium carbonate is 10:1-5:1.
4. The method for synthesizing a benzindole compound according to claim 1, wherein the molar ratio of the naphthylamine compound to the vinylene carbonate is 10.0:1.0-1.0:2.0.
5. The method for synthesizing a benzindole compound according to claim 1, wherein the concentration of vinylene carbonate in the solvent is 0.1 to 0.2 mol/liter.
6. The method for synthesizing the benzindole compound according to claim 1, wherein the specific conditions of the reaction are as follows: heating and stirring 2 h-24 h in an oil bath at 80-150deg.C.
7. The method for synthesizing a benzindole compound according to claim 1, wherein the solvent is one or a mixture of hexafluoroisopropanol, toluene and trifluoroacetic acid in any ratio.
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CN109678878A (en) * 2019-02-27 2019-04-26 陕西科技大学 A kind of benzothiophene and coumarin kind compound and its synthetic method
CN113912529A (en) * 2021-09-13 2022-01-11 成都大学 Method for synthesizing indole compound by catalyzing N-aryl amide compound and vinylene carbonate with ruthenium

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Publication number Priority date Publication date Assignee Title
CN109678878A (en) * 2019-02-27 2019-04-26 陕西科技大学 A kind of benzothiophene and coumarin kind compound and its synthetic method
CN113912529A (en) * 2021-09-13 2022-01-11 成都大学 Method for synthesizing indole compound by catalyzing N-aryl amide compound and vinylene carbonate with ruthenium

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