CN104370797A - Synthesis method of 3-halooxindole derivatives - Google Patents

Synthesis method of 3-halooxindole derivatives Download PDF

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CN104370797A
CN104370797A CN201410598206.9A CN201410598206A CN104370797A CN 104370797 A CN104370797 A CN 104370797A CN 201410598206 A CN201410598206 A CN 201410598206A CN 104370797 A CN104370797 A CN 104370797A
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diazonium
methyl
halo
oxoindole
phenyl amide
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胡文浩
黄海峰
马超群
车久威
邢栋
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East China Normal University
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East China Normal University
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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
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/32—Oxygen atoms
    • C07D209/34—Oxygen atoms in position 2

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  • Organic Chemistry (AREA)
  • Indole Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention discloses a synthesis method of 3-halooxindole and derivatives thereof disclosed as Formula (I). Phenyl amide diazonium and NXS used as raw materials are subjected to one-step reaction to obtain the 3-halooxindole derivatives. By avoiding using the expensive transition metal catalyst and using the cheap and accessible NXS as the raw material, the method has the advantages of mild reaction conditions, fewer reaction steps, high reaction speed, low cost, fewer generated wastes, high atomic economical efficiency and high safety and reliability, and is simple to operate.

Description

A kind of synthetic method of 3-halo oxoindole derivative
Technical field
The present invention relates to synthesis field of medicine and chemical technology, be specifically related to a kind of quick, green 3-halo oxoindole derivative and chemical synthesis process thereof.
Background technology
3-halo Oxoindole is widely used in the middle of complete synthesis application, such as document Org.Lett., Vol.7, No.4, in 2005, author Raymond L.Funk has just used 3-bromine oxoindole derivative by step base catalysis elimination and a ring closure reaction, obtains (±)-flustramine A and (±)-flustramine C analogue.Different spirane structure product can also be taken by different derivative.And developed the synthetic method of a series of 3-halo Oxoindole in the past few decades, as the Oxoindole by 3-hydroxyl obtains (Organic Letters, 2005, vol.7,4531-4534) by the effect of oxalyl chloride and alkali; With the ketal of phenyl amide, the effect of DMSO, TiCl4 generate 3-halo oxoindole derivative (Tetrahedron, 1998, vol.54, p.4889-4898).But, above method also exist severe reaction conditions, the reagent of use or transition-metal catalyst, mostly relate to polystep reaction thus pilot process can produce a large amount of chemical wastes, and length consuming time, high in cost of production defect, therefore aforesaid method is all unfavorable for the application of 3-halo Oxoindole in organic synthesis and industrialization synthesis thereof.
Summary of the invention
The present invention overcomes the above-mentioned defect of prior art, discloses a kind of syntheti c route short, reacts the synthetic method of 3-halo Oxoindole reliable, simple to operate.The present invention devises and is raw material with phenyl amide diazonium and NXS, only just prepares the method for 3-halo Oxoindole through single step reaction.Compared to the synthetic method reported, present method have avoid using expensive transition-metal catalyst, with NXS cheap and easy to get be raw material, reaction conditions is gentle, reactions steps is few, reaction is fast, cost is low, the refuse of generation is few, Atom economy high, therefore the method has very wide application prospect in complete synthesis and pharmaceutical synthesis field.
The present invention proposes a kind of synthetic method of 3-halo oxoindole derivative, and with phenyl amide diazonium and NXS for raw material, obtain 3-halo Oxoindole through single step reaction, its reaction equation is such as formula shown in (A):
Wherein, R 1for hydrogen, p-methyl, p-methoxyl group, p-fluorine, p-chlorine, p-bromine, o-methyl, o-bromine or 2,6-dichloro; R 2for methyl or benzyl; R 3for methyl, ethyl or benzyl; X is chlorine, bromine or iodine.Preferably, R 1for hydrogen, p-methyl, p-methoxyl group, p-chlorine, p-bromine, o-methyl; R 2for methyl, benzyl; R 3for methyl, ethyl.More preferably, R 1for hydrogen, to methyl, p-bromine, adjacent methyl; R 2for methyl.
The 3-halo oxoindole derivative that the inventive method prepares, as shown in following formula (I),
Wherein, R 1for hydrogen, p-methyl, p-methoxyl group, p-fluorine, p-chlorine, p-bromine, o-methyl, o-bromine or 2,6-dichloro; R 2for methyl or benzyl; R 3for methyl, ethyl or benzyl; X is chlorine, bromine or iodine.Preferably, R 1for hydrogen, p-methyl, p-methoxyl group, p-chlorine, p-bromine, o-methyl; R 2for methyl, benzyl; R 3for methyl, ethyl.More preferably, R 1for hydrogen, to methyl, p-bromine, adjacent methyl; R 2for methyl.
In the inventive method, described NXS is dissolved in solvent, at 0 DEG C, phenyl amide diazo solution is slowly joined in described NXS solution, simultaneously vigorous stirring; After phenyl amide diazonium dropwises, at 0 DEG C, continue stirring 10 minutes, until the consumption of phenyl amide diazonium is complete; Then solvent removing is obtained crude product, by ethyl acetate by underpressure distillation: sherwood oil=1: 15 obtain the 3-halo oxoindole derivative shown in straight product formula (I) for eluent carries out column chromatography to crude product.
The synthetic method of the 3-halo Oxoindole of the present invention's design, comprises the following steps: by phenyl amide diazonium: NXS=1.0: 1.0 mol ratios, take raw material.Described NXS is dissolved in solvent, makes the solution of NXS, described phenyl amide diazonium is dissolved in solvent, makes the solution of phenyl amide diazonium.At 0 DEG C, the solution of phenyl amide diazonium is slowly joined in described NXS solution, simultaneously vigorous stirring; After phenyl amide diazonium dropwises, at 0 DEG C, continue stirring 10 minutes, until the consumption of phenyl amide diazonium is complete; Then underpressure distillation crude product that solvent is removed, rear ethyl acetate: sherwood oil=1: 15 obtain straight product for eluent carries out column chromatography to crude product.
In the inventive method, described NXS (N-N-halosuccinimides) is NCS (N-chlorosuccinimide), NBS (N-bromo-succinimide), NIS (N-N-iodosuccinimide).
In the inventive method, described phenyl amide diazonium is without the phenyl amide diazonium replacing or have replacement on phenyl.
In the inventive method, in described phenyl amide diazonium, atom N there is substituting group.
In the inventive method, in described phenyl amide diazonium, there is replacement on limit to diazonium.
In the inventive method, described solvent is methylene dichloride, chloroform, 1,2-ethylene dichloride, tetracol phenixin, tetrahydrofuran (THF), ether, toluene, ethanol.
Preparation method of the present invention, avoids using expensive transition-metal catalyst, and with N-N-halosuccinimides cheap and easy to get for raw material, reaction conditions is gentle, reactions steps is few, and consuming time short, cost is low, the refuse produced is few, and Atom economy is high, simple to operate safe and reliable.Formula (I) the 3-halo oxoindole derivative that the present invention prepares similar have notable biological activity gather indoline alkaloid structure complete synthesis in have a wide range of applications.
Accompanying drawing explanation
Fig. 1 is embodiment 1 products therefrom 1h NMR schematic diagram.
Fig. 2 is embodiment 1 products therefrom 13c NMR schematic diagram.
Fig. 3 is embodiment 2 products therefrom 1h NMR schematic diagram.
Fig. 4 is embodiment 2 products therefrom 13c NMR schematic diagram.
Fig. 5 is embodiment 3 products therefrom 1h NMR schematic diagram.
Fig. 6 is embodiment 3 products therefrom 13c NMR schematic diagram.
Fig. 7 is embodiment 4 products therefrom 1h NMR schematic diagram.
Fig. 8 is embodiment 4 products therefrom 13c NMR schematic diagram.
Fig. 9 is embodiment 5 products therefrom 1h NMR schematic diagram.
Figure 10 is embodiment 5 products therefrom 13c NMR schematic diagram.
Figure 11 is embodiment 6 products therefrom 1h NMR schematic diagram.
Figure 12 is embodiment 6 products therefrom 13c NMR schematic diagram.
Figure 13 is embodiment 7 products therefrom 1h NMR schematic diagram.
Figure 14 is embodiment 7 products therefrom 13c NMR schematic diagram.
Figure 15 is embodiment 8 products therefrom 1h NMR schematic diagram.
Figure 16 is embodiment 8 products therefrom 13c NMR schematic diagram.
Figure 17 is embodiment 9 products therefrom 1h NMR schematic diagram.
Figure 18 is embodiment 9 products therefrom 13c NMR schematic diagram.
Figure 19 is embodiment 10 products therefrom 1h NMR schematic diagram.
Figure 20 is embodiment 10 products therefrom 13c NMR schematic diagram.
Figure 21 is embodiment 11 products therefrom 1h NMR schematic diagram.
Figure 22 is embodiment 11 products therefrom 13c NMR schematic diagram.
Figure 23 is embodiment 12 products therefrom 1h NMR schematic diagram.
Figure 24 is embodiment 12 products therefrom 13c NMR schematic diagram.
Embodiment
In conjunction with following specific embodiments and the drawings, the present invention is described in further detail.Implement process of the present invention, condition, reagent, experimental technique etc., except the following content mentioned specially, be universal knowledege and the common practise of this area, the present invention is not particularly limited content.
Embodiment 1
NBS (5.0mmol) is dissolved in methylene dichloride (10mL), at 0 DEG C, the methylene dichloride (5mL) that is dissolved in of methyl-N-methyl diazonium Acetanilide (5.0mmol) is joined in NBS solution in 60 minutes, stirs at 0 DEG C simultaneously; After methyl-N-methyl diazonium Acetanilide solution dropwises, at 0 DEG C, continue stirring 10 minutes, until the consumption of phenyl amide diazonium is complete; Then solvent is removed to obtain crude product by underpressure distillation; By crude product ethyl acetate: sherwood oil=1: 15 obtain straight product (1.14g, yield=95%) for eluent carries out column chromatography.
1H NMR(400MHz，CDCl 3)δ7.44(d，J＝7.5Hz，1H)，7.33(t，J＝7.8Hz，1H)，7.12(t，J＝7.5Hz，1H)，6.84(d，J＝7.8Hz，1H)，3.24(s，3H)，2.04(s，3H).
13C NMR(100MHz，CDCl 3)δ174.78，141.78，131.67，130.10，124.12，123.39，108.75，52.39，26.72，26.36.
Embodiment 2
NCS (5.0mmol) is dissolved in methylene dichloride (10mL), at 0 DEG C, the methylene dichloride (5mL) that is dissolved in of methyl-N-methyl diazonium Acetanilide (5.0mmol) is joined in NCS solution in 60 minutes, stirs at 0 DEG C simultaneously; After methyl-N-methyl diazonium Acetanilide solution dropwises, at 0 DEG C, continue stirring 10 minutes, until the consumption of phenyl amide diazonium is complete; Then solvent is removed to obtain crude product by underpressure distillation; By crude product ethyl acetate: sherwood oil=1: 15 obtain straight product (0.82g, yield=85%) for eluent carries out column chromatography.
1H NMR(400MHz，CDCl 3)δ7.43(d，J＝7.4Hz，1H)，7.35(td，J＝7.8，1.1Hz，1H)，7.13(td，J＝7.4，0.7Hz，1H)，6.86(d，J＝7.8Hz，1H)，3.24(s，3H)，1.90(s，3H).
13C NMR(100MHz，CDCl 3)δ174.41，142.12，131.05，130.18，123.79，123.43，108.71，61.81，26.63，25.92.
Embodiment 3
NIS (5.0mmol) is dissolved in methylene dichloride (10mL), at 0 DEG C, the methylene dichloride (5mL) that is dissolved in of methyl-N-methyl diazonium Acetanilide (5.0mmol) is joined in NIS solution in 60 minutes, stirs at 0 DEG C simultaneously; After methyl-N-methyl diazonium Acetanilide solution dropwises, at 0 DEG C, continue stirring 10 minutes, until the consumption of phenyl amide diazonium is complete; Then solvent is removed to obtain crude product by underpressure distillation; By crude product ethyl acetate: sherwood oil=1: 15 obtain straight product (1.37g, yield=96%) for eluent carries out column chromatography.
1H NMR(400MHz，CDCl 3)δ7.45(dd，J＝7.5，0.8Hz，1H)，7.30(td，J＝7.8，1.2Hz，1H)，7.09(td，J＝7.5，0.8Hz，1H)，6.79(d，J＝7.8Hz，1H)，3.23(s，3H)，2.14(s，3H).
13C NMR(100MHz，CDCl 3)δ176.71，140.73，133.92，129.57，124.30，123.33，108.84，30.62，28.88，26.87.
Embodiment 4
NBS (5.0mmol) is dissolved in methylene dichloride (10mL), at 0 DEG C, the methylene dichloride (5mL) that is dissolved in of methyl-N-methyl diazonium acetyl open-chain crown ether (5.0mmol) is joined in NBS solution in 60 minutes, stirs at 0 DEG C simultaneously; After methyl-N-methyl diazonium acetyl open-chain crown ether solution dropwises, at 0 DEG C, continue stirring 10 minutes, until the consumption of phenyl amide diazonium is complete; Then solvent is removed to obtain crude product by underpressure distillation; By crude product ethyl acetate: sherwood oil=1: 15 obtain straight product (1.16g, yield=92%) for eluent carries out column chromatography.
1H NMR(400MHz，CDCl 3)δ7.26(s，1H)，7.13(d，J＝7.9Hz，1H)，6.72(d，J＝7.9Hz，1H)，3.22(s，3H)，2.36(s，3H)，2.02(s，3H).
13C NMR(100MHz，CDCl 3)δ174.74，139.40，133.10，131.62，130.41，124.82，108.52，52.76，26.73，26.41，21.04.
Embodiment 5
NBS (5.0mmol) is dissolved in methylene dichloride (10mL), at 0 DEG C, the methylene dichloride (5mL) that is dissolved in of methyl-N-methyl diazonium acetyl P-nethoxyaniline (5.0mmol) is joined in NBS solution in 60 minutes, stirs at 0 DEG C simultaneously; After methyl-N-methyl diazonium acetyl P-nethoxyaniline solution dropwises, at 0 DEG C, continue stirring 10 minutes, until the consumption of phenyl amide diazonium is complete; Then solvent is removed to obtain crude product by underpressure distillation; By crude product ethyl acetate: sherwood oil=1: 15 obtain straight product (1.21g, yield=90%) for eluent carries out column chromatography.
1H NMR(400MHz，CDCl 3)δ7.26(s，1H)，7.13(d，J＝6.9Hz，1H)，6.72(d，J＝6.9Hz，1H)，3.22(s，3H)，2.36(s，3H)，2.02(s，3H).
13C NMR(100MHz，CDCl 3)δ174.74，171.98，139.40，133.10，131.62，130.41，124.82，108.51，52.76，26.73，26.41，21.03.
Embodiment 6
NBS (5.0mmol) is dissolved in methylene dichloride (10mL), at 0 DEG C, the methylene dichloride (5mL) that is dissolved in of methyl-N-methyl diazonium acetyl para-fluoroaniline (5.0mmol) is joined in NBS solution in 60 minutes, stirs at 0 DEG C simultaneously; After methyl-N-methyl diazonium acetyl para-fluoroaniline solution dropwises, at 0 DEG C, continue stirring 10 minutes, until the consumption of phenyl amide diazonium is complete; Then solvent is removed to obtain crude product by underpressure distillation; By crude product ethyl acetate: sherwood oil=1: 15 obtain straight product (1.20g, yield=93%) for eluent carries out column chromatography.
1H NMR(400MHz，CDCl 3)δ7.18(d，J＝7.3Hz，1H)，7.04(t，J＝8.7Hz，1H)，6.81-6.71(m，1H)，3.23(s，3H)，2.02(s，3H).
13C NMR(100MHz，CDCl 3)δ174.49，160.75，158.34，137.71，133.11，133.03，116.58，116.35，112.34，112.09，109.47，109.39，51.67，26.87，26.27.
Embodiment 7
NBS (5.0mmol) is dissolved in methylene dichloride (10mL), at 0 DEG C, the methylene dichloride (5mL) that is dissolved in of methyl-N-methyl diazonium acetyl p-Chlorobenzoic acid amide (5.0mmol) is joined in NBS solution in 60 minutes, stirs at 0 DEG C simultaneously; After methyl-N-methyl diazonium acetyl p-Chlorobenzoic acid amide solution dropwises, at 0 DEG C, continue stirring 10 minutes, until the consumption of phenyl amide diazonium is complete; Then solvent is removed to obtain crude product by underpressure distillation; By crude product ethyl acetate: sherwood oil=1: 15 obtain straight product (1.28g, yield=94%) for eluent carries out column chromatography.
1H NMR(400MHz，CDCl 3)δ7.42(s，1H)，7.31(d，J＝8.3Hz，1H)，6.77(d，J＝8.3Hz，1H)，3.23(s，3H)，2.02(s，3H).
13C NMR(100MHz，CDCl 3)δ174.31，140.30，133.17，130.00，128.78，124.66，109.76，51.34，26.85，26.23.
Embodiment 8
NBS (5.0mmol) is dissolved in methylene dichloride (10mL), at 0 DEG C, the methylene dichloride (5mL) that is dissolved in of methyl-N-methyl diazonium acetyl para-bromoaniline (5.0mmol) is joined in NBS solution in 60 minutes, stirs at 0 DEG C simultaneously; After methyl-N-methyl diazonium acetyl para-bromoaniline solution dropwises, at 0 DEG C, continue stirring 10 minutes, until the consumption of phenyl amide diazonium is complete; Then solvent is removed to obtain crude product by underpressure distillation; By crude product ethyl acetate: sherwood oil=1: 15 obtain straight product (1.49g, yield=94%) for eluent carries out column chromatography.
1H NMR(400MHz，CDCl 3)δ7.55(d，J＝1.8Hz，1H)，7.46(dd，J＝8.3，1.9Hz，1H)，6.72(d，J＝8.3Hz，1H)，3.23(s，3H)，2.02(s，3H).
13C NMR(100MHz，CDCl 3)δ174.21，140.80，133.52，132.90，127.42，115.90，110.24，51.24，26.83，26.24.
Embodiment 9
NBS (5.0mmol) is dissolved in methylene dichloride (10mL), at 0 DEG C, the methylene dichloride (5mL) that is dissolved in of methyl-N-methyl diazonium acetyl o-toluidine (5.0mmol) is joined in NBS solution in 60 minutes, stirs at 0 DEG C simultaneously; After methyl-N-methyl diazonium acetyl o-methyl-benzene amine aqueous solution dropwises, at 0 DEG C, continue stirring 10 minutes, until the consumption of phenyl amide diazonium is complete; Then solvent is removed to obtain crude product by underpressure distillation; By crude product ethyl acetate: sherwood oil=1: 15 obtain straight product (1.23g, yield=97%) for eluent carries out column chromatography.
1H NMR(400MHz，CDCl 3)δ7.29(d，J＝7.3Hz，1H)，7.05(d，J＝7.3Hz，1H)，6.99(t，J＝7.3Hz，1H)，3.52(s，3H)，2.58(s，3H)，2.01(s，3H).
13C NMR(100MHz，CDCl 3)δ175.53，139.49，133.76，132.25，123.30，122.23，120.45，52.38，30.11，26.60，18.88.
Embodiment 10
NBS (5.0mmol) is dissolved in methylene dichloride (10mL), at 0 DEG C, the methylene dichloride (5mL) that is dissolved in of ethyl-N-methyl diazonium Acetanilide (5.0mmol) is joined in NBS solution in 60 minutes, stirs at 0 DEG C simultaneously; After ethyl-N-methyl diazonium Acetanilide solution dropwises, at 0 DEG C, continue stirring 10 minutes, until the consumption of phenyl amide diazonium is complete; Then solvent is removed to obtain crude product by underpressure distillation; By crude product ethyl acetate: sherwood oil=1: 15 obtain straight product (1.13g, yield=89%) for eluent carries out column chromatography.
1H NMR(400MHz，CDCl 3)δ7.39(d，J＝7.3Hz，1H)，7.33(t，J＝7.6Hz，1H)，7.12(t，J＝7.3Hz，1H)，6.84(d，J＝7.6Hz，1H)，3.24(s，3H)，2.40(q，J＝7.3Hz，2H)，0.79(t，J＝7.3Hz，3H).
13C NMR(100MHz，CDCl 3)δ174.19，142.57，129.99，129.73，124.51，123.30，108.66，57.16，32.81，26.65，9.86.
Embodiment 11
NBS (5.0mmol) is dissolved in methylene dichloride (10mL), at 0 DEG C, the methylene dichloride (5mL) that is dissolved in of Benzyl-N-methyl diazonium Acetanilide (5.0mmol) is joined in NBS solution in 60 minutes, stirs at 0 DEG C simultaneously; After Benzyl-N-methyl diazonium Acetanilide solution dropwises, at 0 DEG C, continue stirring 10 minutes, until the consumption of phenyl amide diazonium is complete; Then solvent is removed to obtain crude product by underpressure distillation; By crude product ethyl acetate: sherwood oil=1: 15 obtain straight product (1.35g, yield=86%) for eluent carries out column chromatography.
1H NMR(400MHz，CDCl 3)δ7.39(d，J＝7.4Hz，1H)，7.23(t，J＝7.9Hz，1H)，7.08(m，4H)，6.96(d，J＝6.1Hz，2H)，6.61(d，J＝7.9Hz，1H)，3.70(dd，J＝13.3Hz，2H)，3.03(s，3H).
13C NMR(101MHz，CDCl 3)δ173.77，142.40，134.25，130.37，130.03，129.13，127.96，127.19，125.21，122.99，108.54，56.20，45.37，26.49.
Embodiment 12
NBS (5.0mmol) is dissolved in methylene dichloride (10mL), at 0 DEG C, the methylene dichloride (5mL) that is dissolved in of methyl-N-benzyl diazonium Acetanilide (5.0mmol) is joined in NBS solution in 60 minutes, stirs at 0 DEG C simultaneously; After methyl-N-benzyl diazonium Acetanilide solution dropwises, at 0 DEG C, continue stirring 10 minutes, until the consumption of phenyl amide diazonium is complete; Then solvent is removed to obtain crude product by underpressure distillation; By crude product ethyl acetate: sherwood oil=1: 15 obtain straight product (1.42g, yield=90%) for eluent carries out column chromatography.
1H NMR(400MHz，CDCl 3)δ7.47(d，J＝7.4Hz，1H)，7.39-7.28(m，5H)，7.22(t，J＝7.7Hz，1H)，7.10(t，J＝7.6Hz，1H)，6.72(d，J＝7.8Hz，1H)，4.96(dd，J＝15.8Hz，2H)，2.12(s，3H).
13C NMR(101MHz，CDCl 3)δ174.95，140.85，135.17，131.62，130.00，128.91，127.81，127.12，124.16，123.40，109.81，52.47，43.98，
Protection content of the present invention is not limited to above embodiment.Under the spirit and scope not deviating from inventive concept, the change that those skilled in the art can expect and advantage are all included in the present invention, and are protection domain with appending claims.

Claims (7)

1. a synthetic method for 3-halo oxoindole derivative, is characterized in that, with phenyl amide diazonium and NXS for raw material, obtain 3-halo Oxoindole through single step reaction, its reaction equation is such as formula shown in (A):
Wherein, R 1for hydrogen, p-methyl, p-methoxyl group, p-fluorine, p-chlorine, p-bromine, o-methyl, o-bromine, 2,6-dichloros; R 2for methyl, benzyl; R 3for methyl, ethyl, benzyl; X is chlorine, bromine, iodine;
Described NXS is dissolved in solvent, at 0 DEG C, the solution of phenyl amide diazonium is slowly joined in described NXS solution, simultaneously vigorous stirring; After phenyl amide diazonium dropwises, continue to stir, until the consumption of phenyl amide diazonium is complete at 0 DEG C; Then, underpressure distillation obtains crude product except desolventizing, carries out column chromatography obtain the 3-halo Oxoindole shown in straight product formula (I) to crude product.
2. the synthetic method of 3-halo oxoindole derivative as claimed in claim 1, is characterized in that, mol ratio=1.0 of phenyl amide diazonium: NXS: 1.0.
3. the preparation method of 3-halo Oxoindole according to claim 1, it is characterized in that, described NXS is NCS, NBS, NIS.
4. the preparation method of 3-halo Oxoindole according to claim 1, is characterized in that, described phenyl amide diazonium is without the phenyl amide diazonium replacing or have replacement on phenyl.
5. the preparation method of 3-halo Oxoindole according to claim 1, is characterized in that, atom N has substituting group to described phenyl amide diazonium.
6. the preparation method of 3-halo Oxoindole according to claim 1, is characterized in that, there is replacement on diazonium limit to described phenyl amide diazonium.
7. the preparation method of 3-halo Oxoindole according to claim 1, is characterized in that, described solvent is methylene dichloride, chloroform, 1,2-ethylene dichloride, tetracol phenixin, tetrahydrofuran (THF), ether, toluene, ethanol.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105439937A (en) * 2015-12-02 2016-03-30 苏州大学 Method for synthesizing 3-halogenoindoles-2-one compound
CN106831530A (en) * 2016-12-29 2017-06-13 兰州大学 A kind of method that generation based on acyl group free radical prepares disubstituted Oxoindole

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020055171A1 (en) * 1998-05-27 2002-05-09 Virenda Kumar Tuli Preparation of biologically active 3-methyleneoxindole and definition of its application in stimulation of plant growth and tissue repair
CN101503404A (en) * 2009-03-16 2009-08-12 华东师范大学 Preparation of 3-substituted-3-hydroxy-indole-2-ketone bis-heterocyclic derivative
CN102516151A (en) * 2011-11-11 2012-06-27 华东师范大学 3-substituted-3-hydroxyindazolone derivatives, and preparation method and application thereof
CN102531995A (en) * 2011-12-31 2012-07-04 华东师范大学 3,3'-disubstituted-3-hydroxy bis-indolinone derivative and preparation method and application thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020055171A1 (en) * 1998-05-27 2002-05-09 Virenda Kumar Tuli Preparation of biologically active 3-methyleneoxindole and definition of its application in stimulation of plant growth and tissue repair
CN101503404A (en) * 2009-03-16 2009-08-12 华东师范大学 Preparation of 3-substituted-3-hydroxy-indole-2-ketone bis-heterocyclic derivative
CN102516151A (en) * 2011-11-11 2012-06-27 华东师范大学 3-substituted-3-hydroxyindazolone derivatives, and preparation method and application thereof
CN102531995A (en) * 2011-12-31 2012-07-04 华东师范大学 3,3'-disubstituted-3-hydroxy bis-indolinone derivative and preparation method and application thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ANTHONY MARFAT，等: "OXIDATION OF INDOLES WITH PYRIDINIUM BROMIDE PERBROMIDE A SIMPLE AND EFFICIENT SYNTHESIS OF 7-AZAOXINDOLES", 《TETRAHEDRON LETTERS》, vol. 28, no. 35, 31 December 1987 (1987-12-31), pages 4027 - 4030, XP027128057 *
YOU-QUAN ZOU，等: "Visible-light-induced photocatalytic formyloxylation reactions of 3-bromooxindoles with water and DMF: the scope and mechanism", 《GREEN CHEMISTRY》, 8 May 2014 (2014-05-08), pages 3787 - 3795 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105439937A (en) * 2015-12-02 2016-03-30 苏州大学 Method for synthesizing 3-halogenoindoles-2-one compound
CN106831530A (en) * 2016-12-29 2017-06-13 兰州大学 A kind of method that generation based on acyl group free radical prepares disubstituted Oxoindole

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