CN110372722B - Method for synthesizing sulfur-nitrogen-containing bis-heterocyclic compound - Google Patents

Method for synthesizing sulfur-nitrogen-containing bis-heterocyclic compound Download PDF

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CN110372722B
CN110372722B CN201910805345.7A CN201910805345A CN110372722B CN 110372722 B CN110372722 B CN 110372722B CN 201910805345 A CN201910805345 A CN 201910805345A CN 110372722 B CN110372722 B CN 110372722B
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indole
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CN110372722A (en
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刘建明
王智贤
岳园园
王科
王智玥
邵慧彬
晁君丽
杨焱
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Henan Normal University
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
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Abstract

The invention discloses a method for synthesizing a sulfur-nitrogen-containing diheterocyclic compound, belonging to the technical field of organic chemistry. Indole compounds 1, o-bromobenzaldehyde compounds 2 and sulfur simple substances are used as raw materials, and are heated and reacted in the presence of sodium carbonate to obtain polysubstituted sulfur-nitrogen-containing bis-heterocyclic compounds 3. The invention utilizes indole compounds, 2-bromobenzaldehyde compounds and sulfur simple substances to construct the functional polysubstituted sulfur-nitrogen-containing diheterocyclic compound by one step under the metal-free condition, and has simple method and wide substrate application range.

Description

Method for synthesizing sulfur-nitrogen-containing bis-heterocyclic compound
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing sulfur-nitrogen-containing bis-heterocyclic compounds.
Background
Heterocyclic compounds are widely found in nature, and most of the biologically important compounds are heterocyclic compounds such as nucleic acids, certain vitamins, antibiotics, hormones, pigments, alkaloids, and the like. In addition, heterocyclic compounds having various properties are important components in pharmaceuticals, and some of them are useful as pharmaceuticals, insecticides, herbicides, dyes, plastics, and the like.
The sulfur or nitrogen heterocyclic ring molecule and sulfur-nitrogen containing dual heterocyclic compound are all important heterocyclic compounds, and can be used for producing various dyes, spices, rapid cooling and heating resistant plastics, high-activity solvents, stimulants, insecticides, brightening agents, cosmetics, biological activating substances, vitamins, anesthetics, antibiotics and other medicines. The sulfur nitrogen heterocyclic compound has various biological activities, and besides various drug effects of antibiosis, antivirus, anti-inflammation, blood sugar reduction and the like, the anticancer activity gradually draws attention. Due to the potential application prospect in various fields, scientists pay attention to and pay attention to the method, and a great deal of research is carried out on the method, so that a great deal of valuable scientific achievements are obtained.
The traditional method or process for synthesizing the sulfur-nitrogen-containing diheterocyclic compound has more or less defects, such as: (1) expensive metal organic reagents and the like are adopted, so that the cost is high, and the industrial production is not facilitated; (2) high temperature and multi-step reaction are needed, conditions are harsh, and practical application of the reaction is limited; (3) the yield and selectivity are still not high enough to be further improved, etc.
Therefore, the development of a synthetic process of the sulfur-nitrogen-containing diheterocyclic compound with simple operation, low cost and high yield is the target of the majority of researchers, and the synthetic process not only has urgent research value, but also has good industrial application prospect.
Disclosure of Invention
In order to overcome the defects pointed out above and further seek a simple method for synthesizing substituted sulfur-nitrogen-containing bis-heterocyclic compounds, the invention discloses a method for simply, effectively and conveniently synthesizing sulfur-nitrogen-containing bis-heterocyclic compounds. The method for preparing the sulfur-nitrogen-containing bis-heterocyclic compound through one-step reaction under mild reaction conditions from simple and easily available reagents avoids the defects of complex raw materials, harsh conditions and the like of the traditional synthetic method, and successfully synthesizes the multifunctional sulfur-nitrogen-containing bis-heterocyclic compound.
The invention discloses a method for synthesizing sulfur-nitrogen-containing bis-heterocyclic compounds, which adopts the technical scheme and is characterized by comprising the following operations: indole compounds 1, o-bromobenzaldehyde compounds 2 and sulfur simple substances are heated and reacted in an organic solvent in the presence of inorganic base to obtain sulfur-nitrogen-containing bis-heterocyclic compounds 3, and the reaction equation is as follows:
Figure BDA0002183474410000021
wherein: ar (Ar)1Is substituted aryl, and the substituent is selected from hydrogen, methyl, methoxy or halogen; ar is2Substituted aryl or heteroaryl, the substituents being selected from hydrogen, methyl, halogen or trifluoromethyl.
More specifically, compound 1 is indole, 4-methylindole, 5-methylindole, 6-methylindole, 4-methoxyindole, 5-methoxyindole, 7-methoxyindole, 4-chloroindole, 5-chloroindole, 6-chloroindole, 7-chloroindole, 5-fluoroindole, 6-fluoroindole, 4-bromoindole, 5-bromoindole, 7-bromoindole, etc.; the compound 2 is 2-bromobenzaldehyde, 2-bromo-4-methylbenzaldehyde, 2-bromo-5-fluorobenzaldehyde, 2-bromo-5-trifluoromethylbenzaldehyde, 2-bromo-3-pyridinecarboxaldehyde, 1-bromo-2-naphthaldehyde, etc.
Further, in the above technical solution, the inorganic base is selected from any one of sodium carbonate, potassium carbonate, lithium carbonate, cesium carbonate, and sodium hydrogen carbonate. Preferably, the inorganic base is sodium carbonate.
Further, in the above technical scheme, the reaction temperature during the heating reaction is 100-140 ℃; further, the optimum temperature is 130 ℃.
Further, in the above technical solution, the reaction solvent is selected from DMF, DMAC, DMSO; still further, preferably the solvent is DMF.
Further, in the technical scheme, the molar ratio of the indole compound 1, the o-bromoformaldehyde compound 2 and the elemental sulfur to the alkali is 1:3:3:4, and the reaction can achieve the optimal reaction effect under the condition of the ratio.
Further, in the above technical scheme, the reaction is preferably carried out under the protection of nitrogen.
Further, for better understanding of the present invention, when indole 1a and o-bromobenzaldehyde 2a are used as substrates, sodium carbonate is used as an inorganic base, and DMF is used as a solvent, the conditions are optimized as follows: under nitrogen atmosphere, 0.25mmol indole 1a, 0.75mmol 2-bromobenzaldehyde 2a, 0.75mmol sulfur, 1.0mmol sodium carbonate and 2mL DMF were sequentially added into a Schlenk reaction tube, and the mixture was heated to 130 ℃ in IKA (constant temperature magnetic stirrer) at constant temperature and stirred for reaction for 20 h. After the reaction was completed, it was cooled to room temperature and quenched with distilled water. Then extracted with ethyl acetate (3X 20 mL). The organic layers were combined and the organic phase was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The pure product 3a is obtained by column chromatography separation with the yield of 71 percent.
Figure BDA0002183474410000031
When other conditions were unchanged, only the following reaction conditions were changed, and the results were as follows:
1) when the using amount of the sulfur simple substance is adjusted to 1.0mmol and 0.50mmol, the separation yield is 41 percent and 24 percent respectively.
2) The inorganic base was replaced with potassium carbonate, lithium carbonate, cesium carbonate and sodium bicarbonate, and the isolation yields were 50%, 24%, 28% and 48%, respectively.
3) With other reaction solvents such as DMSO, DMAC, the yields were 43% and 57%, respectively.
4) The reaction yields correspond to 50% and 56% at reaction temperatures of 110 ℃ and 140 ℃, respectively.
To further understand the reaction mechanism, the following comparative experiments were performed, and the reaction equation is expressed as follows:
Figure BDA0002183474410000041
from the above reaction experiment, the reaction mechanism is presumed to be:
Figure BDA0002183474410000051
advantageous effects of the invention
1) The method has the advantages of few experimental steps, low technical difficulty, mild conditions and easy operation. The method avoids the use of a multi-step reaction process, and the reaction can be completed in one step.
2) The invention synthesizes a novel sulfur-nitrogen-containing diheterocyclic compound through the oxidative coupling reaction of indole compounds, 2-bromobenzaldehyde compounds and elemental sulfur.
The specific embodiment is as follows:
the above-mentioned contents of the present invention are further described in detail by the following examples, but it should not be construed that the scope of the above-mentioned subject matter of the present invention is limited to the following examples, and any technologies realized based on the above-mentioned contents of the present invention are within the scope of the present invention.
Examples 1 to 16
Under the nitrogen atmosphere, 0.25mmol indole compound 1a-p, 0.75mmol o-bromobenzaldehyde compound 2a, 0.75mmol sulfur, 1.0mmol sodium carbonate and 2mLDMF were sequentially added into a Schlenk reaction tube, and the mixture was heated to 130 ℃ at constant temperature in a constant temperature magnetic stirrer and stirred for reaction for 20 hours. After the reaction was completed, it was cooled to room temperature and quenched with distilled water. Then extracted with ethyl acetate (3X 20 mL). And combining the organic layers, drying the organic phase by anhydrous sodium sulfate, and performing column chromatography separation on the crude product obtained by rotary evaporation to obtain the pure product 3a-3 p. The results are shown in the following table:
Figure BDA0002183474410000061
Figure BDA0002183474410000062
Figure BDA0002183474410000071
Standard condition：1a(1equiv，0.25mmol)，2a(3equiv，0.75mmol)，S8(3equiv，0.75mmol)，Na2CO3(4equiv，1.0mmol)，DMF(2mL)，N2，130℃，20h.
characterization data for compounds 3a-3p are as follows:
Thiochromeno[2，3-b]indole 3a，71％；1H NMR(600MHz，CDCl3)8.20(s，1H)，7.92(d，J＝6.0Hz，1H)，7.79(d，J＝6.0Hz，1H)，7.70(t，J＝6.0Hz，2H)，7.50(q，J＝8.0Hz，2H)，7.43(t，J＝9.0Hz，1H)，7.27(t，J＝9.0Hz，1H).13C NMR(151MHz，CDCl3)160.9，154.0，132.3，131.5，130.4，130.1，128.6，128.6，125.7，125.6，125.2，124.7，121.4，119.7，117.6.HRMS，calculated for C15H10NS(M+H+)：236.0528，found：236.0528.
10-methylthiochromeno[2，3-b]indole 3b，57％；1H NMR(600MHz，CDCl3)8.28(s，1H)，7.86(d，J＝6.0Hz，1H)，7.74(d，J＝12.0Hz，1H)，7.58(d，J＝12.0Hz,1H),7.53(t,J＝6.0Hz,1H),7.47(t,J＝9.0Hz,1H),7.42(t,J＝9.0Hz,1H),7.07(d,J＝12.0Hz,1H),2.76(s,3H).13C NMR(151MHz,CDCl3)161.8,155.0,134.3,133.4,133.3,132.8,129.5,129.3,127.0,126.6,126.5,126.1,124.8,123.7,116.5,20.4.HRMS,calculated for C16H12NS(M+H+):250.0685,found:250.0685.
9-methylthiochromeno[2,3-b]indole 3c,41％；1H NMR(600MHz,CDCl3)8.30(d,J＝6.0Hz,1H),7.88(dd,J＝12.0,6.0Hz,1H),7.79(d,J＝12.0Hz,2H),7.62(d,J＝6.0Hz,1H),7.57(t,J＝9.0Hz,1H),7.50(t,J＝6.0Hz,1H),7.35(d,J＝12.0Hz,1H),2.51(s,3H).13C NMR(151MHz,CDCl3)161.1,153.1,133.4,132.5,132.1,131.5,130.7,130.7,129.5,126.7,126.7,126.1,125.9,121.2,118.2,21.5.HRMS,calculated for C16H12NS(M+H+):250.0685,found:250.0685.
8-methylthiochromeno[2,3-b]indole 3d,55％；1H NMR(600MHz,CDCl3)8.26(d,J＝12.0Hz,1H),7.86(td,J＝12.0,6.0Hz,2H),7.78(t,J＝12.0Hz,1H),7.57-7.48(m,3H),7.12(t,J＝9.0Hz,1H),2.53(d,J＝6.0Hz,3H).13C NMR(151MHz,CDCl3)162.1,155.4,140.3,133.0,132.4,131.3,130.1,129.3,126.8,126.7,126.2,123.6,123.1,120.5,119.1,22.3.HRMS,calculated for C16H12NS(M+H+):250.0685,found:250.0685.
10-methoxythiochromeno[2,3-b]indole 3e,59％；1H NMR(600MHz,CDCl3)8.47(s,1H),7.78(d,J＝6.0Hz,1H),7.66(d,J＝6.0Hz,1H),7.42(td,J＝9.0,6.0Hz,1H),7.37(q,J＝8.0Hz,2H),7.28(d,J＝12.0Hz,1H),6.70(d,J＝6.0Hz,1H),3.97(s,3H).13C NMR(151MHz,CDCl3)162.0,156.8,156.3,133.5,132.6,132.5,130.5,130.4,129.1,127.4,126.6,126.1,113.6,111.8,104.5,55.5.HRMS,calculated for C16H12NOS(M+H+):266.0634,found:266.0634.
9-methoxythiochromeno[2,3-b]indole 3f,93％；1H NMR(600MHz,CDCl3)8.24(s,1H),7.85(d,J＝6.0Hz,1H),7.75(d,J＝12.0Hz,1H),7.61(d,J＝6.0Hz,1H),7.55(td,J＝9.0,6.0Hz,1H),7.48(td,J＝9.0,6.0Hz,2H),7.10(dd,J＝12.0,6.0Hz,1H),3.90(s,3H).13C NMR(151MHz,CDCl3)160.0,156.1,149.4,133.5,132.6,131.6,131.1,129.6,126.7,126.7,126.5,126.1,119.0,116.5,105.7,56.0.HRMS,calculated for C16H12NOS(M+H+):266.0634,found:266.0634.
7-methoxythiochromeno[2,3-b]indole 3g,91％；1H NMR(600MHz,CDCl3)8.35(s,1H),7.88(d,J＝6.0Hz,1H),7.79(d,J＝6.0Hz,1H),7.62(d,J＝6.0Hz,1H),7.56(t,J＝9.0Hz,1H),7.49(t,J＝9.0Hz,1H),7.25(d,J＝6.0Hz,1H),7.05(d,J＝12.0Hz,1H),4.05(s,3H).13C NMR(151MHz,CDCl3)160.0,149.9,143.8,133.9,132.6,132.2,131.6,129.7,127.3,126.8,126.6,126.2,123.4,113.4,111.4,55.9.HRMS,calculated for C16H12NOS(M+H+):266.0634,found:266.0634.
10-chlorothiochromeno[2,3-b]indole 3h,79％；1H NMR(600MHz,CDCl3)8.95(s,1H),7.96(d,J＝12.0Hz,1H),7.82(d,J＝6.0Hz,1H),7.65(d,J＝12.0Hz,1H),7.60(t,J＝6.0Hz,1H),7.53(t,J＝9.0Hz,1H),7.46(t,J＝6.0Hz,1H),7.28(d,J＝6.0Hz,1H).13CNMR(151MHz,CDCl3)162.4,156.2,135.3,133.3,133.1,130.2,130.0,129.7,129.4,126.6,126.6,126.4,123.4,122.6,117.2.HRMS,calculated for C15H9ClNS(M+H+):270.0139,found:270.0139.
9-chlorothiochromeno[2,3-b]indole 3i,67％；1H NMR(600MHz,CDCl3)8.40(s,1H),7.99(s,1H),7.96(d,J＝6.0Hz,1H),7.86(d,J＝6.0Hz,1H),7.65(td,J＝9.0,6.0Hz,2H),7.57(td,J＝9.0,6.0Hz,1H),7.51(dd,J＝12.0,6.0Hz,1H).13C NMR(151MHz,CDCl3)162.2,153.4,133.8,132.9,132.4,130.7,130.2,129.6,128.2,127.1,126.9,126.5,126.5,120.8,119.5.HRMS,calculated for C15H9ClNS(M+H+):270.0139,found:270.0139.
8-chlorothiochromeno[2,3-b]indole 3j,62％；1H NMR(600MHz,CDCl3)8.32(s,1H),7.91(dd,J＝12.0,6.0Hz,1H),7.87(d,J＝12.0Hz,1H),7.82(d,J＝6.0Hz,1H),7.67(s,1H),7.61(t,J＝6.0Hz,1H),7.54(t,J＝6.0Hz,1H),7.25(s,1H).13C NMR(151MHz,CDCl3)163.3,155.7,135.3,133.4,132.8,131.9,130.5,130.0,126.9,126.6,124.1,122.7,121.3,118.9.HRMS,calculated for C15H9ClNS(M+H+):270.0139,found:270.0139.
9-fluorothiochromeno[2,3-b]indole 3k,49％；1H NMR(600MHz,CDCl3)8.34(s,1H),7.92(dd,J＝12.0,6.0Hz,1H),7.83(d,J＝6.0Hz,1H),7.68-7.64(m,2H),7.62(td,J＝9.0,6.0Hz,1H),7.54(td,J＝9.0,6.0Hz,1H),7.25(d,J＝6.0Hz,1H).13C NMR(151MHz,CDCl3)161.6,160.2,158.6,151.2,133.8,132.8,132.2,131.1,131.1,130.1,126.9,126.4,126.4,119.3,119.2,116.8,116.7,107.6,107.4.HRMS,calculated for C15H9FNS(M+H+):254.0434,found:254.0434.
8-fluorothiochromeno[2,3-b]indole 3l,67％；1H NMR(600MHz,CDCl3)8.35(s,1H),7.95(t,J＝6.0Hz,2H),7.85(d,J＝12.0Hz,1H),7.63(t,J＝9.0Hz,1H),7.56(t,J＝6.0Hz,1H),7.41(dd,J＝12.0,6.0Hz,1H),7.04(td,J＝9.0,6.0Hz,1H).13C NMR(151MHz,CDCl3)165.0,163.7,163.3,156.5,156.4,133.0,132.6,130.9,130.6,129.7,126.8,126.6,126.5,121.8,121.6,121.5,110.0,109.9,105.9,105.8.HRMS,calculated forC15H9FNS(M+H+):254.0434,found:254.0434.7-chlorothiochromeno[2,3-b]indole 3m,84％；1H NMR(600MHz,CDCl3)8.30(s,1H),7.92(t,J＝9.0Hz,2H),7.82(d,J＝6.0Hz,1H),7.60(t,J＝6.0Hz,1H),7.54(t,J＝9.0Hz,1H),7.39(dd,J＝12.0,6.0Hz,1H),7.02(t,J＝9.0Hz,1H).13C NMR(151MHz,CDCl3)162.7,151.5,134.0,132.9,131.4,130.2,129.6,127.6,127.0,126.5,126.5,123.6,123.1,119.2.HRMS,calculated for C15H9ClNS(M+H+):270.0139,found:270.0139.
10-bromothiochromeno[2,3-b]indole 3n,51％；1H NMR(600MHz,CDCl3)9.09(s,1H),7.94(d,J＝6.0Hz,1H),7.78(d,J＝12.0Hz,1H),7.68(d,J＝6.0Hz,1H),7.57(td,J＝9.0,6.0Hz,1H),7.49(td,J＝9.0,6.0Hz,1H),7.44(d,J＝6.0Hz,1H),7.38(t,J＝9.0Hz,1H),13C NMR(151MHz,CDCl3)162.4,156.5,135.1,133.5,133.1,130.9,130.1,129.9,126.6,126.6,126.4,126.4,124.3,117.8,117.5.HRMS,calculated for C15H9BrNS(M+H+):313.9634,found:313.9634.
9-bromothiochromeno[2,3-b]indole 3o,52％；1H NMR(600MHz,CDCl3)8.43(s,1H),8.16(s,1H),7.98(d,J＝6.0Hz,1H),7.88(d,J＝6.0Hz,1H),7.66(td,J＝9.0,6.0Hz,2H),7.62(d,J＝12.0Hz,1H),7.58(t,J＝6.0Hz,1H).13C NMR(151MHz,CDCl3)134.8,133.9,132.9,132.5,132.4,130.6,130.2,127.6,126.9,126.5,126.0,125.4,123.8,120.0,115.8.HRMS,calculated for C15H9BrNS(M+H+):313.9634,found:313.9634.
7-bromothiochromeno[2,3-b]indole 3p,88％；1H NMR(600MHz,DMSO-d6)9.13(s,1H),8.23(t,J＝12.0Hz,2H),8.16(d,J＝6.0Hz,1H),7.81(t,J＝9.0Hz,1H),7.77(d,J＝6.0Hz,1H),7.72(t,J＝9.0Hz,1H),7.30(t,J＝6.0Hz,1H),13C NMR(151MHz,DMSO-d6)162.1,152.6,135.5,134.0,133.2,132.4,131.4,131.0,128.0,127.6,127.5,126.7,124.3,121.3,111.9.HRMS,calculated for C15H9BrNS(M+H+):313.9634,found:313.9634.
in examples 1 to 14, various coupling reactions of indole compounds, 2-bromobenzaldehyde and elemental sulfur, in which benzene rings are substituted by electron-withdrawing groups and electron-donating groups, and heterocyclic rings are substituted, were studied. According to the experiments, the reaction has wide substrate adaptability to alkyl, methoxy, chloro, bromo, fluoro and other substituents and heterocycles of a benzene ring, and a corresponding target product with high yield is obtained.
Examples 17 to 21
Under the nitrogen atmosphere, 0.25mmol indole 1a, 0.75mmol o-bromobenzaldehyde compound 2b-g, 1.0mmol sulfur simple substance, 1.0mmol sodium carbonate and 2mLDMF were sequentially added into a Schlenk reaction tube, and the mixture was heated to 130 ℃ at constant temperature in a constant temperature magnetic stirrer and stirred for reaction for 20 hours. After the reaction was completed, it was cooled to room temperature and quenched with distilled water. Then extracted with ethyl acetate (3X 20 mL). And combining the organic layers, drying the organic phase by anhydrous sodium sulfate, and performing column chromatography separation on the crude product obtained by rotary evaporation to obtain a pure product 3q-3 u. The results are shown in the following table:
Figure BDA0002183474410000121
Figure BDA0002183474410000122
Reaction condition：1a(1equiv，0.25mmol)，2b-2g(3equiv，0.75mmol)，S8(4equiv，1.0mmol)，Na2CO3(4equiv，1.0mmol)，DMF(2mL)，130℃，12h.
characterization data for compounds 3q-3u are as follows:
benzo[7,8]thiochromeno[2,3-b]indole 3q,33％；1H NMR(600MHz,CDCl3)8.49(t,J＝9.0Hz,2H),8.06(d,J＝12.0Hz,1H),7.92(d,J＝6.0Hz,1H),7.86(d,J＝12.0Hz,1H),7.80(q,J＝8.0Hz,2H),7.70-7.64(m,2H),7.58(t,J＝6.0Hz,1H),7.34(t,J＝6.0Hz,1H).13C NMR(151MHz,CDCl3)161.0,154.9,133.1,132.6,132.1,131.1,129.7,129.0,128.9,128.6,127.6,126.8,125.3,124.6,123.1,122.4,121.0,118.7.HRMS,calculatedfor C19H12NS(M+H+):286.0685,found:286.0685.
thiochromeno[2,3-b]indole 3r,26％；1H NMR(600MHz,CDCl3)8.38(s,1H),8.03(d,J＝6.0Hz,1H),7.84(d,J＝6.0Hz,1H),7.75(d,J＝6.0Hz,1H),7.66(s,1H),7.55(t,J＝6.0Hz,1H),7.36-7.31(m,2H),2.54(s,3H).13C NMR(151MHz,CDCl3)161.9,154.9,140.8,133.7,132.4,131.3,130.7,129.4,127.8,126.9,125.9,122.4,120.6,118.6,21.8.HRMS,calculated for C16H12NS(M+H+):250.0685,found:250.0685.
2-fluorothiochromeno[2,3-b]indole 3s,33％；1H NMR(600MHz,CDCl3)8.31(s,1H),8.03(d,J＝6.0Hz,1H),7.80(t,J＝6.0Hz,1H),7.74(d,J＝12.0Hz,1H),7.63(dd,J＝12.0,6.0Hz,1H),7.58(t,J＝9.0Hz,1H),7.39-7.33(m,2H).13C NMR(151MHz,CDCl3)162.0,161.5,159.9,155.4,132.4,130.3,129.8,129.7,128.5,128.4,128.3,128.1,128.1,125.4,122.7,121.1,118.8,118.1,118.0,117.8,117.7.HRMS,calculated forC15H9FNS(M+H+):254.0434,found:254.0434.
2-(trifluoromethyl)thiochromeno[2,3-b]indole 3t,33％；1H NMR(600MHz,CDCl3)8.41(s,1H),8.19(s,1H),8.05(d,J＝12.0Hz,1H),7.96(d,J＝6.0Hz,1H),7.81(d,J＝12.0Hz,1H),7.77(d,J＝6.0Hz,1H),7.60(t,J＝6.0Hz,1H),7.38(t,J＝9.0Hz,1H).13CNMR(151MHz,CDCl3)161.1,155.2,136.9,132.8,130.5,129.8,129.2,129.2,129.2,127.5,126.7,125.5,125.5,125.4,123.1,121.2,119.0.HRMS,calculated forC16H9F3NS(M+H+):304.0402,found:304.0402.pyrido[3',2':5,6]thiopyrano[2,3-b]indole 3u,55％；1H NMR(600MHz,DMSO-d6)8.94(s,1H),8.85(d,J＝6.0Hz,1H),8.54(d,J＝12.0Hz,1H),8.23(d,J＝6.0Hz,1H),7.70(td,J＝12.0,6.0Hz,2H),7.59(t,J＝6.0Hz,1H),7.40(td,J＝9.0,6.0Hz,1H),13C NMR(151MHz,DMSO-d6)162.4,155.3,154.5,151.3,140.9,131.6,131.3,130.4,126.0,124.0,123.5,122.6,122.3,119.0.HRMS,calculated forC16H9F3NS(M+H+):237.0481,found:237.0481.
the foregoing embodiments have described the general principles, principal features and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are merely illustrative of the principles of the present invention, and that various changes and modifications may be made without departing from the scope of the principles of the present invention, and the invention is intended to be covered by the appended claims.

Claims (8)

1. A method for synthesizing a sulfur-nitrogen-containing bis-heterocyclic compound is characterized by comprising the following operations: indole compounds 1, o-bromobenzaldehyde compounds 2 and sulfur elementary substances are heated and reacted in an organic solvent in the presence of inorganic base to obtain sulfur-nitrogen-containing bis-heterocyclic compounds 3, and the reaction equation is as follows:
Figure FDA0002420833240000011
wherein the compound 1 is indole, 4-methylindole, 5-methylindole, 6-methylindole, 4-methoxyindole, 5-methoxyindole, 7-methoxyindole, 4-chloroindole, 5-chloroindole, 6-chloroindole, 7-chloroindole, 5-fluoroindole, 6-fluoroindole, 4-bromoindole, 5-bromoindole and 7-bromoindole; the compound 2 is 2-bromobenzaldehyde, 2-bromo-4-methylbenzaldehyde, 2-bromo-5-fluorobenzaldehyde, 2-bromo-5-trifluoromethylbenzaldehyde, 2-bromo-3-pyridinecarboxaldehyde and 1-bromo-2-naphthaldehyde.
2. The method for synthesizing sulfur-nitrogen containing bis-heterocyclic compounds according to claim 1, wherein: the inorganic base is selected from any one of sodium carbonate, potassium carbonate, lithium carbonate, cesium carbonate and sodium bicarbonate.
3. The method for synthesizing sulfur-nitrogen containing bis-heterocyclic compounds according to claim 1 or 2, characterized in that: the inorganic base is selected from sodium carbonate.
4. The method for synthesizing sulfur-nitrogen containing bis-heterocyclic compounds according to claim 1, wherein: the organic solvent is selected from DMSO, DMF or DMAC.
5. The method for synthesizing sulfur-nitrogen containing bis-heterocyclic compounds according to claim 1 or 4, wherein: the organic solvent is selected from DMF.
6. The method for synthesizing sulfur-nitrogen containing bis-heterocyclic compounds according to claim 1, wherein: the molar ratio of the indole compound 1, the o-bromoformaldehyde compound 2, the elemental sulfur and the inorganic base is 1:2-4:3-4: 4.
7. The method for synthesizing sulfur-nitrogen containing bis-heterocyclic compounds according to claim 1, wherein: the temperature during the heating reaction is 100-140 ℃.
8. The method for synthesizing sulfur-nitrogen containing bis-heterocyclic compounds according to claim 1, wherein: the reaction was carried out under nitrogen.
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CN105669698A (en) * 2016-02-25 2016-06-15 青岛科技大学 Preparation method of polysubstituted thiapyran diindyl derivative

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CN105669698A (en) * 2016-02-25 2016-06-15 青岛科技大学 Preparation method of polysubstituted thiapyran diindyl derivative

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6，11-二氢苯并噻喃并［4，3-b］吲哚类化合物的合成及其抗肿瘤活性;张晓旭，等;《合成化学》;20151231;第23卷(第4期);284-288页 *
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