CN104230785A - 3-((4-chlorobenzene base) thio)-5-bromide-1-hydrogen-indole composite method - Google Patents
3-((4-chlorobenzene base) thio)-5-bromide-1-hydrogen-indole composite method Download PDFInfo
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- VXWVFZFZYXOBTA-UHFFFAOYSA-N Brc1ccc2[nH]ccc2c1 Chemical compound Brc1ccc2[nH]ccc2c1 VXWVFZFZYXOBTA-UHFFFAOYSA-N 0.000 description 1
- DFMIXBZFCJBXEU-UHFFFAOYSA-N Cc(cc1)ccc1SC1=CC2NC2c(cc2)c1cc2Br Chemical compound Cc(cc1)ccc1SC1=CC2NC2c(cc2)c1cc2Br DFMIXBZFCJBXEU-UHFFFAOYSA-N 0.000 description 1
- SFECBIMUZPGDAW-UHFFFAOYSA-N Cc(cc1)ccc1SSc(cc1)ccc1Cl Chemical compound Cc(cc1)ccc1SSc(cc1)ccc1Cl SFECBIMUZPGDAW-UHFFFAOYSA-N 0.000 description 1
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- 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
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Abstract
The invention provides a 3-((4-chlorobenzene base) thio)-5-bromide-1-hydrogen-indole composite method. 5-bromine indole and 4, 4 '-dichloro diphenyl disulfide ether serve as raw materials and are dissolved in an alcohol and water mixed solvent, an reaction is performed for 30 to 60 hours in the presence of strong base under the 80 to 140 DEG C and 5 to 15 pressure conditions, and the purified 3-((4-chlorobenzene base) thio)-5- bromide-1-hydrogen-indole is obtained through aftertreatment. According to the 3-((4-chlorobenzene base) thio)-5- bromide-1-hydrogen-indole composite method, the reaction conditions are mild, metal does not need to be added for metal catalysis in the reaction process, the gas protection is not required, and accordingly the difficulty of the treatment after the reaction is reduced, the reaction cost is greatly reduced, the pollution to the environment is reduced, and emissions of the waste are reduced.
Description
Technical field
The present invention relates to a kind of synthetic method of indole derivatives, the synthetic method of the bromo-1-hydrogen-indoles of especially a kind of 3-((4-chloro-phenyl-) sulfo-)-5-.
Background technology
Indoles and derivative thereof have bioactive material, especially the indoles of 3 sulphur virtueizations and derivative thereof, there is very strong biological activity, it is of many uses, first can as pharmaceutical intermediate, synthesis can treat the medicine of the diseases such as the infection of such as heart trouble, obesity, cancer, allergy, bacterium; Secondly, the indoles of some 3 sulphur virtueization and derivative thereof even can be directly medicinal, such as can as inhibitors of cyclooxygenases etc.; In addition, the indoles of 3 sulphur virtueizations and derivative thereof also have certain application in dyestuff, agrochemicals etc.
The indoles of 3 sulphur virtueizations and derivative thereof are that indoles and derivative thereof and disulphide or mercaptan are synthesized, the system mainly containing four large relative maturity in prior art synthesizes indoles and the derivative thereof of 3 sulphur virtueizations: the first kind, and disulphide is as sulphur source and indoles and derivatives reaction thereof; The second, thiophenol is as sulphur source; The third, the phthalic imidine of N-virtue sulfuration is as sulphur source; 4th kind, aryl sulfonyl chloride is as sulphur source.
1988, the people such as Joseph G.Atkinson are just studied the reaction with diaryl disulfide of indoles and derivative thereof, any transition metal is not used only to add NaH in this reaction, preliminary discussion is carried out to reaction mechanism, has thought and just make 3 sulphur virtueization indoles be synthesized because aryl sulfide has good group leaving capability.
2004, the discoveries such as Yasunari Maeda, under vanadium catalysis, indoles and thiol reactant obtained the product of 3 sulphur virtueizations, reaction needed O
2atmosphere, uses N
2protect and generate without spawn, add free radical inhibitors BHT productive rate and be significantly improved.Therefore the reaction mechanism proposed is thought, O
2participating in catalytic cycle process is necessary thing, adds BHT and effectively can suppress this process, thus make mercaptan and indole reaction, therefore can improve reaction yield to a great extent because mercaptan in reaction process preferentially can form disulphide.
2006, the people such as Matthew Tudge, with the N-virtue phthalic imidine of sulfuration and indoles and derivatives reaction thereof, under the catalysis of halide-ions, obtained the corresponding product of a series of 3 sulphur virtueizations.Owing to adding MgBr in reaction
2, therefore think when originally inquiring into mechanism, metal ion and imido carbonyl coordination weaken N-S key and enhance the Electron Affinities of S and be easy to and indole reaction.But further test proof, metal-salt can not effective catalyzed reaction, but halide-ions in action, under its catalysis, the N-S bond rupture of the phthalic imidine of N-virtue sulfuration also forms SULPHURYL CHLORIDE with it, SULPHURYL CHLORIDE is same indole reaction again, obtains target product while taking off halide-ions.Therefore from mechanism, the formation of SULPHURYL CHLORIDE is most critical.
People's SULPHURYL CHLORIDE such as 1980, Morton Raban and indole reaction have been worth the indoles yield of 3 sulphur hydrocarbonylations to reach more than 50%.
For above reaction method, although can obtain 3 sulphur virtueization indoles and the derivative thereof of a great deal of, but still exist a lot of not enough, such as these reactions need to use precious metal or transition metal mostly, such as Pd, Cu, Ni, Co etc., react and be just accomplished under the catalysis of metal; The noxious solvents such as frequent use DMF, DMSO, acetonitrile, benzene, toluene; Some reaction also needs gas shield.First, the use of metal not only can cause very large pollution to environment, makes the aftertreatment of reaction more complicated, also increases reaction cost; Secondly, noxious solvent is volatile, and its use not only also causes very large health threat to people to environment; Reactant gases is protected, and condition is harsher, is not easy to production-scale extension.These problems cause reaction to be difficult to realize mass-producing above, are difficult to be applied in actual production, science and technology cannot be changed into economic interests, and this just reduces the meaning of scientific research to a great extent.
Summary of the invention
In order to overcome the deficiencies in the prior art, the invention provides the synthetic method of the bromo-1-hydrogen-indoles of a kind of 3-((4-chloro-phenyl-) sulfo-)-5-, it is simple that this synthetic method has reaction conditions, cost is low, being easy to extensive extension and producing and the few advantage of environmentally friendly pollution.
To achieve these goals, the technical solution used in the present invention is: the synthetic method of the bromo-1-hydrogen-indoles of a kind of 3-((4-chloro-phenyl-) sulfo-)-5-, it is characterized in that: with 4 shown in the 5-bromo indole shown in formula I and formula II, 4 '-dichloro disulfide is raw material, raw material is dissolved in alcohols-water mixed solvent, under highly basic existence condition, react 30 ~ 60 hours under 80 ~ 140 DEG C, 5 ~ 15 pressure conditions, obtain formula III crude product, this chemical equation is as follows:
Described 4,4 '-dichloro disulfide is 1: 0.25 ~ 4 with the amount of substance ratio of 5-bromo indole, described 5-bromo indole is 1: 0.2 ~ 1 with the amount of substance ratio of highly basic, the volume ratio of alcohols and water is 1: 0.5 ~ 5, the volumetric usage of mixed solvent and 4, the mass ratio of 4 '-dichloro disulfide is 50 ~ 100mL/g.
As the further setting of the present invention, described highly basic is the one in tetra-n-butyl aqua ammonia, sodium hydroxide, potassium hydroxide.
As the further setting of the present invention, described 5-bromo indole is 1: 0.4 ~ 0.8 with the amount of substance ratio of tetra-n-butyl aqua ammonia.
As the further setting of the present invention, described alcoholic solvent is ethanol or Virahol, and the volume ratio of alcohols and water is 1: 1.5 ~ 1.6.
As the further setting of the present invention, described 4,4 '-dichloro disulfide is 1: 0.5 ~ 1 with the amount of substance ratio of 5-bromo indole.
As the further setting of the present invention, the volumetric usage of described mixed solvent and 4, the mass ratio of 4 '-dichloro disulfide is 70 ~ 80mL/g.
As the further setting of the present invention, described reaction whole process is through TLC tracking monitor.
As the further setting of the present invention, also comprise and purification processes is carried out to crude product, this purification processes comprises the following steps: after reaction terminates, reaction solution is cooled to room temperature and treats that solid is separated out, obtain filtrate and filter cake through suction filtration, filtrate is extracted with ethyl acetate, and gets organic layer drying, steaming desolventizes and obtains solid, solid and filter cake are merged, obtains thick product and purify through silicagel column; Described purification first washes a silicagel column with the sherwood oil of boiling range 60 ~ 90 DEG C, then by thick product loading, then is that eluent carries out column chromatography with the mixed solution that the sherwood oil of boiling range 60 ~ 90 DEG C and the volume ratio of ethyl acetate are 5: 2, collects R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains the bromo-1-hydrogen-indoles of 3-((4-chloro-phenyl-) sulfo-)-5-shown in formula III.
Adopt such scheme, instant invention overcomes the various defects of the method for synthesizing 3 sulphur virtueization indoles and derivative thereof in prior art, have found the method for the bromo-1-hydrogen-indoles of a kind of ideal synthesis 3-((4-chloro-phenyl-) sulfo-)-5-.This reaction is carried out under comparatively gentle condition, has prepared a kind of desirable indoles and has had the bromo-1-hydrogen-indoles of bioactive pharmaceutical intermediate 3-((4-chloro-phenyl-) sulfo-)-5-.And reaction process is without the need to adding metal catalytic, without the need to gas shield, completes each reaction under relatively mild conditions and obtaining target product with higher productive rate.This reaction system be different from the most outstanding feature of other reaction systems be not add any metal catalytic, reaction solvent to can carry out under environment almost pollution-free, air conditions, undesirable gas protection atmosphere.
This reaction mechanism is as follows:
Under aqueous basic conditions, 4, S-S in 4 '-dichloro disulfide ruptures, generate sulfonium ion and an electronegative sulfonium ion of a positively charged, but the sulfonium ion of positively charged is combined with hydroxide ion in the basic conditions, generates a kind of sulfuryl chloride that is similar to vivaciously and obtain intermediate as shown in Formula I V, 3 that formula IV attack 5-bromo indole is active, there is electrophilic substitution, generate product III and water.Wherein tetra-n-butyl aqua ammonia not only provides alkaline environment, and plays the effect of buffer reagent, can maintain the pH value of solution, stablize reaction environment.Simultaneously, tetra-n-butyl aqua ammonia also plays the effect of phase-transfer catalyst, can promote to dissolve, reactant is fully contacted, so effect is best, but other highly basic are as also passable in the mineral alkali such as sodium hydroxide, potassium hydroxide in addition, but there is no the damping fluid of tetra-n-butyl aqua ammonia and the effect of phase-transfer catalyst due to such inorganic strong alkali, so add the height that the reaction yield of such inorganic strong alkali and efficiency do not have tetra-n-butyl aqua ammonia.In addition, because the sulphur of positively charged generated in this reaction is unstable under alkaline environment, so the comparatively small amt generated, therefore 4, it is excessive that 4 '-dichloro disulfide needs in the reaction.But by this reaction, do not need metal-complexing and gas shield to carry out realization response, still very simple, the above-mentioned crude product be obtained by reacting also needs to carry out purifying process by aftertreatment and obtains real required product.
The amount of substance ratio of above-mentioned 5-bromo indole and tetra-n-butyl aqua ammonia, preferably 1: 0.4 ~ 0.8, the setting of this ratio considers the double factor of efficiency and cost, if increase the amount of tetra-n-butyl aqua ammonia again, improve few of its efficiency but cost can increase on the contrary greatly, few, then efficiency is not high, therefore this compares for preferred setting.Alcoholic solvent is ethanol or Virahol, and the volume ratio of alcohols and water is 1: 1.5 ~ 1.6, ethanol and Virahol have good solubility to material, are conducive to the fracture of disulfide linkage, in addition, other alcohols such as methyl alcohol primary isoamyl alcohol, propyl carbinol, isopropylcarbinol, amylalcohol, hexanol etc. are also suitable for, but efficiency do not have ethanol and Virahol good, also can be suitable for as long as other organic solvent and water dissolve each other, but consider that the efficiency of ethanol and Virahol is high, cost is low and to features such as the friendly of environment, select ethanol and Virahol as solvent.
The invention has the beneficial effects as follows:
1, environmental pollution is little: whole reaction process did not use metal catalyst, has stopped metallic pollution, and the pollution that reaction produces can control less, can realize green production.And solvent for use is water and alcohols, almost pollution-free to environment.
2, the bromo-1-hydrogen-indoles of 3-((4-chloro-phenyl-) sulfo-)-5-not only has the biological activity of indoles, and on phenyl ring and indole ring, have a halogen atom respectively, for enter next step synthesis or base group modification provide active reaction sites, be desirable pharmaceutical intermediate.
3, this reaction system has very strong advantage, reduces the difficulty of post-reaction treatment, greatly reduces reaction cost, improve productive rate, also reduces the pollution to environment, decreases the discharge of waste.This is expanded the scale of production further and effectively increases economic efficiency and serve keying action.
Below in conjunction with accompanying drawing, the invention will be further described.
Accompanying drawing explanation
Accompanying drawing 1 is that the nucleus magnetic resonance H of synthetic product of the present invention composes;
Accompanying drawing 2 is that the nucleus magnetic resonance C of synthetic product of the present invention composes;
Accompanying drawing 3 is the high resolution spectrogram of synthetic product of the present invention.
Embodiment
Below in conjunction with specific embodiment, the invention will be further described, but protection scope of the present invention is not limited thereto.
With 4 shown in the 5-bromo indole shown in formula I and formula II, 4 '-dichloro disulfide is raw material, at water, ethanol or Virahol volume ratio are in the mixed solvent of 1: 1.5 ~ 1.6, under tetra-n-butyl aqua ammonia exists, at 80 ~ 140 DEG C, react 30 ~ 60 hours under 5 ~ 15 pressure conditions, TLC tracking monitor is to reacting completely, after reaction terminates, reaction solution is cooled to room temperature, solid is had to separate out, suction filtration obtains filtrate and filter cake, filtrate is extracted with ethyl acetate, get organic layer drying, steaming desolventizes and obtains solid, merge with described filter cake, obtain thick product to purify through silicagel column, described purification first washes a silicagel column with the sherwood oil of boiling range 60 ~ 90 DEG C, then by thick product loading, then is that eluent carries out column chromatography with the mixed solution that the sherwood oil of boiling range 60 ~ 90 DEG C and the volume ratio of ethyl acetate are 5: 2, collects R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains the bromo-1-hydrogen-indoles of 3-((4-chloro-phenyl-) sulfo-)-5-shown in formula III.
The testing conditions of product is: wherein
13c NMR and
1h NMR Bruker Aance-500 nmr determination; Product column chromatography (silica gel 200-300 order) purifies and separates; The WRS-1B numeral melting point instrument that the fusing point of compound is produced by Shanghai Shen Guang instrument company limited measures; High resolution mass spectrum Bruker company ESI-Q-q-TOF mass spectrograph measures.
Table 1
Carry out the proportioning of material according to table 1, obtain following specific embodiment:
Embodiment 1
By 0.235mmol (0.046g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.047mmol (0.012g) tetra-n-butyl aqua ammonia, then add the mixing solutions 21ml (V of second alcohol and water
ethanol: V
water=1: 1.5) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.050g, productive rate 63%.Tan solid, mp:257-259 DEG C.
1H?NMR(500MHz，DMSO)δ11.95(s，1H)，7.87(d，J＝2.6Hz，1H)，7.48(d，J＝8.8Hz，2H)，7.33-7.27(m，3H)，7.02(d，J＝8.6Hz，2H)；
13CNMR(126MHz，DMSO)δ137.8，135.5，134.3，130.4，129.6，128.9，127.0，124.9，120.2，114.6，113.，98.6.MS(ESI-Qq-TOF)m/z(amu)calcd?for?C
14H
10BrClNS[M+H]
+：337.9405.Found：337.9400.Anal.calcd?for?C
14H
9BrClNS(％)：C，49.65；H，2.68；N，4.14.Found：C，49.72；H，2.71；N，4.23.
Embodiment 2
By 3.760mmol (0.736g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.752mmol (0.192g) tetra-n-butyl aqua ammonia, then add the mixing solutions 21ml (V of second alcohol and water
ethanol: V
water=1: 1.5) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.582g, productive rate 46%.
Embodiment 3
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.094mmol (0.024g) tetra-n-butyl aqua ammonia, then add the mixing solutions 21ml (V of second alcohol and water
ethanol: V
water=1: 1.5) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.108g, productive rate 68%.
Embodiment 4
By 0.940mmol (0.184g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.188mmol (0.048g) tetra-n-butyl aqua ammonia, then add the mixing solutions 21ml (V of second alcohol and water
ethanol: V
water=1: 1.5) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.133g, productive rate 42%.
Embodiment 5
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.188mmol (0.048g) tetra-n-butyl aqua ammonia, then add the mixing solutions 21ml (V of second alcohol and water
ethanol: V
water=1: 1.6). low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.111g, productive rate 70%.
Embodiment 6
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.376mmol (0.096g) tetra-n-butyl aqua ammonia, then add the mixing solutions 21ml (V of second alcohol and water
ethanol: V
water=1: 1.6) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.114g, productive rate 72%.
Embodiment 7
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.235mmol (0.059g) tetra-n-butyl aqua ammonia, then add the mixing solutions 21ml (V of second alcohol and water
ethanol: V
water=1: 1.6) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.110g, productive rate 70%.
Embodiment 8
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.4700.235mmol (0.118g) tetra-n-butyl aqua ammonia, then add the mixing solutions 21ml (V of second alcohol and water
ethanol: V
water=1: 1.6) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.115g, productive rate 73%.
Embodiment 9
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.235mmol (0.059g) tetra-n-butyl aqua ammonia, then add the mixing solutions 21ml (V of second alcohol and water
ethanol: V
water=1: 0.2) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.071g, productive rate 45%.
Embodiment 10
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.235mmol (0.059g) tetra-n-butyl aqua ammonia, then add the mixing solutions 21ml (V of second alcohol and water
ethanol: V
water=1: 1.5) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.110g, productive rate 70%.
Embodiment 11
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.235mmol (0.059g) tetra-n-butyl aqua ammonia, then add the mixing solutions 21ml (V of second alcohol and water
ethanol: V
water=1: 3) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.090g, productive rate 57%.
Embodiment 12
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.235mmol (0.059g) tetra-n-butyl aqua ammonia, then add the mixing solutions 21ml (V of second alcohol and water
ethanol: V
water=1: 5) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.079g, productive rate 50%.
Embodiment 13
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.235mmol (0.059g) tetra-n-butyl aqua ammonia, then add the mixing solutions 21ml (V of second alcohol and water
virahol: V
water=1: 0.2) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.074g, productive rate 47%.
Embodiment 14
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.235mmol (0.059g) tetra-n-butyl aqua ammonia, then add the mixing solutions 21ml (V of second alcohol and water
virahol: V
water=1: 1.5) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.109g, productive rate 69%.
Embodiment 15
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.235mmol (0.059g) tetra-n-butyl aqua ammonia, then add the mixing solutions 21ml (V of second alcohol and water
virahol: V
water=1: 3) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.095g, productive rate 60%.
Embodiment 16
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.235mmol (0.059g) tetra-n-butyl aqua ammonia, then add the mixing solutions 21ml (V of second alcohol and water
virahol: V
water=1: 5) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.081g, productive rate 51%.
Embodiment 17
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 ' dichloro disulfide puts into beaker, add 0.235mmol (0.059g) tetra-n-butyl aqua ammonia, then add the mixing solutions 15ml (V of second alcohol and water
ethanol: V
water=1: 5) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.076g, productive rate 48%.
Embodiment 18
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.235mmol (0.059g) tetra-n-butyl aqua ammonia, then add the mixing solutions 30ml (V of second alcohol and water
ethanol: V
water=1: 5) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.064g, productive rate 41%.
Embodiment 19
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.235mmol (0.059g) tetra-n-butyl aqua ammonia, then add the mixing solutions 24ml (V of second alcohol and water
ethanol: V
water=1: 5) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.080g, productive rate 50%.
Embodiment 20
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.235mmol (0.010g) sodium hydroxide, then add the mixing solutions 21ml (V of second alcohol and water
ethanol: V
water=1: 1.6) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.100g, productive rate 63%.
Embodiment 21
By 0.470mmol (0.092g) 5-bromo indole and 0.940mmol (0.284g) 4,4 '-dichloro disulfide puts into beaker, add 0.235mmol (0.013g) potassium hydroxide, then add the mixing solutions 21ml (V of second alcohol and water
ethanol: V
water=1: 1.6) low-grade fever stirs, then mixing solutions being proceeded to 30ml is with in the stainless steel pressure still of Teflon lining, be heated to 130 DEG C, under automatic boosting, react 48h, TLC tracking and measuring reactant 5-bromo indole disappears, then room temperature is naturally cooled to, have Tan solid to generate, suction filtration gets solid, simultaneously mother liquor 170ml extraction into ethyl acetate, get organic over anhydrous dried over mgso, rotate solvent evaporated and obtain solid.Two portions solids mixing is thick product.First go over pillar with the sherwood oil of boiling range 60 ~ 90 DEG C, by thick product loading, then with volume ratio be 5: 2 the sherwood oil of boiling range 60 ~ 90 DEG C and the mixed solution of ethyl acetate be that eluent carries out column chromatography, collection R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains 3-((4-chloro-phenyl-) sulfo-)-5-bromo-1 hydrogen-indoles, 0.102g, productive rate 65%.
Above-mentioned specific embodiment 1-4, its variable is 5-bromo indole and 4, the amount of substance ratio of 4 '-dichloro disulfide, can 4 be learnt by embodiment 1-4, the amount of substance of 4 '-dichloro disulfide and 5-bromo indole is optimum ratio than 1: 0.5, and see embodiment 3, its productive rate is 68%; In specific embodiment 5-8, its variable is tetra-n-butyl aqua ammonia and the amount of substance ratio of 5-bromo indole, and its optimum ratio is 1: 0.5, sees embodiment 8, and its productive rate is 73%; In specific embodiment 7,9-12, its variable is in mixed solvent, the volume ratio of ethanol and water, and be preferably 1: 1.5-1.6, see embodiment 7 and embodiment 10, its productive rate all reaches 70%; Specific embodiment 13-16 is visible, and the volume ratio 1: 1.5 of Virahol and water is optimum ratio.
Claims (8)
1. the synthetic method of the bromo-1-hydrogen-indoles of 3-((4-chloro-phenyl-) sulfo-)-5-, it is characterized in that: with 4 shown in the 5-bromo indole shown in formula I and formula II, 4 '-dichloro disulfide is raw material, raw material is dissolved in alcohols-water mixed solvent, under highly basic existence condition, react 30 ~ 60 hours under 80 ~ 140 DEG C, 5 ~ 15 pressure conditions, obtain formula III crude product, this chemical equation is as follows:
Described 4,4 '-dichloro disulfide is 1: 0.25 ~ 4 with the amount of substance ratio of 5-bromo indole, described 5-bromo indole is 1: 0.2 ~ 1 with the amount of substance ratio of highly basic, the volume ratio of alcohols and water is 1: 0.5 ~ 5, the volumetric usage of mixed solvent and 4, the mass ratio of 4 '-dichloro disulfide is 50 ~ 100mL/g.
2. the synthetic method of the bromo-1-hydrogen-indoles of 3-according to claim 1 ((4-chloro-phenyl-) sulfo-)-5-, is characterized in that: described highly basic is wherein a kind of in tetra-n-butyl aqua ammonia or sodium hydroxide, potassium hydroxide.
3. the synthetic method of the bromo-1-hydrogen-indoles of 3-according to claim 2 ((4-chloro-phenyl-) sulfo-)-5-, is characterized in that: described 5-bromo indole is 1: 0.4 ~ 0.8 with the amount of substance ratio of tetra-n-butyl aqua ammonia.
4. the synthetic method of the bromo-1-hydrogen-indoles of 3-according to claim 1 ((4-chloro-phenyl-) sulfo-)-5-, it is characterized in that: described alcoholic solvent is ethanol or Virahol, and the volume ratio of alcohols and water is 1: 1.5 ~ 1.6.
5. the synthetic method of the bromo-1-hydrogen-indoles of 3-according to claim 1 ((4-chloro-phenyl-) sulfo-)-5-, it is characterized in that: described 4,4 '-dichloro disulfide is 1: 0.5 ~ 1 with the amount of substance ratio of 5-bromo indole.
6. the synthetic method of the bromo-1-hydrogen-indoles of 3-according to claim 1 ((4-chloro-phenyl-) sulfo-)-5-, it is characterized in that: the volumetric usage of described mixed solvent and 4, the mass ratio of 4 '-dichloro disulfide is 70 ~ 80mL/g.
7. the synthetic method of the bromo-1-hydrogen-indoles of 3-according to claim 1 ((4-chloro-phenyl-) sulfo-)-5-, is characterized in that: described reaction whole process is through TLC tracking monitor.
8. the synthetic method of the bromo-1-hydrogen-indoles of 3-((4-chloro-phenyl-) sulfo-)-5-according to claim 1-7 any one, it is characterized in that: also comprise and purification processes is carried out to crude product, this purification processes comprises the following steps: after reaction terminates, reaction solution is cooled to room temperature and treats that solid is separated out, filtrate and filter cake is obtained through suction filtration, filtrate is extracted with ethyl acetate, get organic layer drying, steaming desolventizes and obtains solid, solid and filter cake are merged, obtains thick product and purify through silicagel column; Described purification first washes a silicagel column with the sherwood oil of boiling range 60 ~ 90 DEG C, then by thick product loading, then is that eluent carries out column chromatography with the mixed solution that the sherwood oil of boiling range 60 ~ 90 DEG C and the volume ratio of ethyl acetate are 5: 2, collects R
fvalue is the elutriant of 0.4, rotates evaporate to dryness eluent, namely obtains the bromo-1-hydrogen-indoles of 3-((4-chloro-phenyl-) sulfo-)-5-shown in formula III.
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Non-Patent Citations (3)
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| CLAUDIO C. SILVEIRA ET AL.: "The use of anhydrous CeCl3 as a catalyst for the synthesis of 3-sulfenyl indoles", 《TETRAHEDRON LETTERS》, vol. 51, 11 February 2010 (2010-02-11), pages 2014 - 2016, XP026946760, DOI: doi:10.1016/j.tetlet.2010.02.038 * |
| JULIANO B. AZEREDO ET AL.: "A Solvent- and Metal-Free Synthesis of 3‑Chacogenyl-indoles Employing DMSO/I2 as an Eco-friendly Catalytic Oxidation System", 《J. ORG. CHEM.》, vol. 79, 8 April 2014 (2014-04-08) * |
| YUNYUN LIU ET AL.: "Synthesis of 3-sulfenylated indoles by a simple NaOH promoted sulfenylation reaction", 《RSC ADV.》, vol. 4, 6 August 2014 (2014-08-06), pages 35528 - 35530 * |
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| CN108586311A (en) * | 2018-03-23 | 2018-09-28 | 温州医科大学 | A kind of preparation method of 3- thioethers indoles or 3- selenide indoles |
| CN108586311B (en) * | 2018-03-23 | 2020-05-26 | 温州医科大学 | Preparation method of 3-thioether indole or 3-seleno-ether indole |
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