CN109678784A - Thioetherification Benzazole compounds and preparation method thereof - Google Patents

Thioetherification Benzazole compounds and preparation method thereof Download PDF

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Publication number
CN109678784A
CN109678784A CN201710980427.6A CN201710980427A CN109678784A CN 109678784 A CN109678784 A CN 109678784A CN 201710980427 A CN201710980427 A CN 201710980427A CN 109678784 A CN109678784 A CN 109678784A
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China
Prior art keywords
thioetherification
indoles
benzazole compounds
reactant
preparation
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CN201710980427.6A
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Chinese (zh)
Inventor
赵霞
苏志扬
芦逵
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Tianjin University
Tianjin Normal University
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Tianjin 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B45/00—Formation or introduction of functional groups containing sulfur
    • C07B45/06—Formation or introduction of functional groups containing sulfur of mercapto or sulfide groups

Abstract

The invention discloses a kind of preparation methods of thioetherification Benzazole compounds, it carries out as steps described below: by catalyst, indoles reactant, hydrazine hydrate, substituted phenyl sulfonyl chlorine and solvent mix to be incorporated at 90~100 DEG C in closed container to be stirred to react 13~15 hours, obtain thioetherification Benzazole compounds, wherein, the indoles reactant, the ratio of the amount of the substance of hydrazine hydrate and substituted phenyl sulfonyl chlorine is 1:1:2, the catalyst is elemental iodine, the solvent is 1, 4- dioxane, compared with the prior art, preparation method raw material of the invention and catalyst are cheap and easily-available, product is made using one kettle way, step is simple, by-product is few.

Description

Thioetherification Benzazole compounds and preparation method thereof
Technical field
The invention belongs to technical field of organic synthesis, a kind of thioetherification Benzazole compounds and its preparation are related in particular to Method.
Background technique
Carbon-sulfide linkage forms reaction and plays very crucial effect in the synthesis of organosulfur compound, and organic sulfur Compound is the important segment and important structural unit of many drug molecules or some material molecules again.Therefore, in recent years to carbon- The exploration of sulfide linkage building new method has caused the concern of many scientists.Building carbon-sulfide linkage main method is to utilize at present Cross metal catalytic, this method is needed with metallic catalyst expensive and to air-sensitive, and sulphur source stench, it is unstable, have and wave Hair property.
Summary of the invention
In view of the deficiencies of the prior art, the purpose of the present invention is to provide a kind of thioetherification Benzazole compounds and its preparations Method, the preparation side prepare thioetherification Benzazole compounds using one kettle way using substituted phenyl sulfonyl chlorine as parent.
The purpose of the present invention is what is be achieved by following technical proposals.
A kind of preparation method of thioetherification Benzazole compounds carries out as steps described below:
Catalyst, indoles reactant, hydrazine hydrate, substituted phenyl sulfonyl chlorine and solvent are mixed in closed container and are incorporated in It is stirred to react at 90~100 DEG C 13~15 hours, obtains thioetherification Benzazole compounds, wherein the indoles reactant, water The ratio for closing the amount of the substance of hydrazine and substituted phenyl sulfonyl chlorine is 1:1:2, and the catalyst is elemental iodine, and the solvent is Isosorbide-5-Nitrae-two Six ring of oxygen, the general structure of the indoles reactant are as follows:
The general structure of the substituted phenyl sulfonyl chlorine are as follows:
Wherein, the R1For hydrogen, hydroxyl or methoxyl group；The R2For hydrogen, the R3For hydrogen, the R4For methyl or methoxy Base.
In the above-mentioned technical solutions, the substituted phenyl sulfonyl chlorine is for paratoluensulfonyl chloride or to Methoxybenzenesulfonyl chloride.
In the above-mentioned technical solutions, using volume ratio is (5~10): the mixture of 1 petroleum ether and ethyl acetate is as flowing It moves the thioetherification Benzazole compounds obtained after opposite be stirred to react and carries out gradient elution, obtain the thioetherification indoles of solid Close object.
In the above-mentioned technical solutions, the time being stirred to react is determined by thin-layered chromatography.
In the above-mentioned technical solutions, the ratio of the amount of the substance of the catalyst and indoles reactant is 1:10.
In the above-mentioned technical solutions, concentration of the indoles reactant in the solvent is 1~1.5mol/L.
A kind of thioetherification Benzazole compounds that above-mentioned preparation method obtains, the structure of the thioetherification Benzazole compounds General formula are as follows:
Wherein, the R1For hydrogen, hydroxyl or methoxyl group；The R2For hydrogen, the R3For hydrogen, the R4For methyl or methoxy Base.
In the above-mentioned technical solutions, the thioetherification Benzazole compounds are 4- hydroxyl -3- [(4- tolyl) sulfydryl]-Yin Diindyl, structural formula are
The indoles reactant is 4- oxyindole, and the substituted phenyl sulfonyl chlorine is paratoluensulfonyl chloride.
In the above-mentioned technical solutions, the thioetherification Benzazole compounds are 6- methoxyl group -3- [(4- tolyl) sulfydryl] - Indoles, structural formula are
The indoles reactant is 6- methoxy-Indole, and the substituted phenyl sulfonyl chlorine is paratoluensulfonyl chloride.
In the above-mentioned technical solutions, the thioetherification Benzazole compounds are 3- [(4- methoxyphenyl) sulfydryl]-indoles, Its structural formula is
The indoles reactant is indoles, and the substituted phenyl sulfonyl chlorine is to Methoxybenzenesulfonyl chloride.
A kind of application of above-mentioned preparation method in sulfide synthesis Benzazole compounds.
Compared with the prior art, preparation method of the invention has the beneficial effect that
1. raw material and catalyst are cheap and easily-available.
2. product is made using one kettle way in experiment, step is simple, and by-product is few.
Detailed description of the invention
Fig. 1 is the general structure of thioetherification Benzazole compounds of the invention.
Specific embodiment
The reaction mechanism of preparation method of the invention are as follows:
Substituted phenyl sulfonyl chlorine first generates intermediate sulfonyl hydrazine in the presence of hydrazine hydrate in situAnd then sulfohydrazide occurs tandem reaction with indoles reactant under elemental iodine catalysis and generates Thioetherification product (thioetherification Benzazole compounds), reaction mechanism are as follows:
Indoles reactant is indoles or Benzazole compounds, using indoles reactant, substituted phenyl sulfonyl chlorine and water It closes hydrazine and carries out tandem reaction under the catalysis of iodine, synthesize a series of thioetherification Benzazole compounds.
The typical thioetherification Benzazole compounds that preparation method of the invention can synthesize are as follows:
1,4- hydroxyl -3- [(4- tolyl) sulfydryl]-indoles
2,6- methoxyl group -3- [(4- tolyl) sulfydryl]-indoles
3,3- [(4- methoxyphenyl) sulfydryl]-indoles
Technical solution of the present invention is further illustrated combined with specific embodiments below.
The name of the thioetherification Benzazole compounds of following embodiment synthesis and structure are as shown in table 1:
The name and structure of 1 thioetherification Benzazole compounds of table
Table 1 synthesizes all indoles reactants used, and purity is 98%, purchase producer: Sa grace chemical technology (on Sea) Co., Ltd's table 1 synthesizes all substituted phenyl sulfonyl chlorine for using, and purity is also all 98%, buys producer: Sa grace chemistry Technology (Shanghai) Co., Ltd..
Instrument and model NMR spectrum (1H NMR) tester of nuclear magnetic resonance, Brucker ARX 400 (400MHz), chemical shift uses tetramethylsilane as internal standard.
Following yield measuring methods: weighing the quality of product first, with the quality of product divided by the molal weight of product, Obtain the amount of the substance of product.It then, must with the amount of the substance of product divided by the amount of the substance of indoles reactant in raw material To the yield of the product.
Embodiment 1
The structural formula of sulfide synthesis Benzazole compounds are as follows:
The preparation method of the thioetherification Benzazole compounds is carried out as steps described below:
4- oxyindole (0.5mmol) and paratoluensulfonyl chloride (0.5mmol) are added in 15mL air-tight bottle, then according to Secondary addition 0.5mL 1,4- dioxane, hydrazine hydrate (1mmol) and elemental iodine (0.05mmol).Screwing hermetic bottleneck, in 90 DEG C Under reaction is sufficiently stirred.It after 15 hours, is detected with thin-layered chromatography, to after completion of the reaction, stop heating.At this point, system is turned 10mL round-bottomed flask is moved to, reduction vaporization is spin-dried for solvent, obtains to column separation object.Then product is divided with silica gel-column chromatography It separates out and (be eluted with petroleum ether: ethyl acetate=10:1), obtaining taupe indoles aryl thioethers solid product, (55.0mg is produced Rate: 43%): mp (melting point)=86-88 DEG C；IR(KBr pellet):3403,3335,1584,1503,1323, 1230,1200,806,733,485cm-1；Through nuclear-magnetism1H NMR measurement,1H NMR(400MHz,CDCl3)δ8.42(s,1H), 7.55 (s, 1H), 7.29 (s, 1H), 7.12 (t, J=7.9Hz, 1H), 7.03 (q, J=8.2Hz, 4H), 6.98-6.93 (m, 1H), 6.60 (d, J=7.7Hz, 1H), 2.25 (s, 3H)
Embodiment 2
The structural formula of sulfide synthesis Benzazole compounds are as follows:
The preparation method of the thioetherification Benzazole compounds is carried out as steps described below:
6- methoxy-Indole (0.5mmol) and paratoluensulfonyl chloride (0.5mmol) are added in 15mL air-tight bottle, then Sequentially add 0.5mL 1,4- dioxane, hydrazine hydrate (1mmol) and elemental iodine (0.05mmol).Screwing hermetic bottleneck, in 90 Reaction is sufficiently stirred at DEG C.After 13 hours, detected with thin-layered chromatography.To after completion of the reaction, stop heating.At this point, by system It is transferred to 10mL round-bottomed flask, reduction vaporization is spin-dried for solvent, obtains to column separation object.Then use silica gel-column chromatography by product It separates and (is eluted with petroleum ether: ethyl acetate=7:1), obtaining faint yellow indoles aryl thioethers solid product, (81.4mg is produced Rate: 61%): mp (melting point)=134-136 DEG C；IR(KBr pellet):3406,1622,1454,1300, 1158,810,506cm-1；It is measured through nuclear-magnetism 1H NMR, 1H NMR (400MHz, CDCl3) δ 8.23 (s, 1H), 7.45 (d, J= 8.7Hz, 1H), 7.35 (d, J=1.9Hz, 1H), 7.05-6.94 (m, 4H), 6.89 (s, 1H), 6.81 (d, J=8.7Hz, 1H), 3.84(s,3H),2.24(s,3H).
Embodiment 3
The structural formula of sulfide synthesis Benzazole compounds are as follows:
The preparation method of the thioetherification Benzazole compounds is carried out as steps described below:
It is added in 15mL air-tight bottle by indoles (0.5mmol) and to Methoxybenzenesulfonyl chloride (0.5mmol), then successively 0.75mL 1,4- dioxane, hydrazine hydrate (1mmol) and elemental iodine (0.05mmol) is added.Screwing hermetic bottleneck, in 100 DEG C Under reaction is sufficiently stirred.After 13 hours, detected with thin-layered chromatography.To after completion of the reaction, stop heating.At this point, system is turned 10mL round-bottomed flask is moved to, reduction vaporization is spin-dried for solvent, obtains to column separation object.Then product is divided with silica gel-column chromatography It separates out and (be eluted with petroleum ether: ethyl acetate=5:1), obtaining faint yellow indoles aryl thioethers solid product, (45.7mg is produced Rate: 36%): mp (melting point)=113-114 DEG C；IR(KBr pellet):3398,2925,1490,1454, 1404,1281,1239,1176,1094,1026,817,737,513cm-1；Through nuclear-magnetism1H NMR measurement,1H NMR(400MHz, CDCl3) δ 8.35 (s, 1H), 7.63 (d, J=7.9Hz, 1H), 7.47 (d, J=2.6Hz, 1H), 7.42 (d, J=8.1Hz, 1H),7.28-7.22(m,1H),7.18–7.11(m,4H),6.75–6.73(m,1H),3.73(s,3H).
Indoles reactant involved in above-described embodiment sulfide synthesis Benzazole compounds and substituted phenyl sulfonyl chlorine Title and structural formula it is as follows:
Indoles
4- oxyindole
6- methoxy-Indole
To Methoxybenzenesulfonyl chloride
Paratoluensulfonyl chloride
In the inventive solutions, by adjusting the type of indoles reactant, substituted phenyl sulfonyl chlorine, reacting temperature Degree and reaction time can reach the consistent property of above-described embodiment.
The subsidy that this patent obtains: the present invention obtains the subsidy (Grant No.: 21572158) of state natural sciences fund.
Illustrative description has been done to the present invention above, it should explanation, the case where not departing from core of the invention Under, any simple deformation, modification or other skilled in the art can not spend the equivalent replacement of creative work equal Fall into protection scope of the present invention.

Claims (10)

1. a kind of preparation method of thioetherification Benzazole compounds, which is characterized in that carry out as steps described below:
Catalyst, indoles reactant, hydrazine hydrate, substituted phenyl sulfonyl chlorine and solvent are mixed in closed container and are incorporated in 90~ It is stirred to react at 100 DEG C 13~15 hours, obtains thioetherification Benzazole compounds, wherein the indoles reactant, hydrazine hydrate Ratio with the amount of the substance of substituted phenyl sulfonyl chlorine is 1:1:2, and the catalyst is elemental iodine, and the solvent is Isosorbide-5-Nitrae-dioxy six Ring, the general structure of the indoles reactant are as follows:
The general structure of the substituted phenyl sulfonyl chlorine are as follows:
Wherein, the R1For hydrogen, hydroxyl or methoxyl group；The R2For hydrogen, the R3For hydrogen, the R4For methyl or methoxy.
2. preparation method according to claim 1, which is characterized in that the substituted phenyl sulfonyl chlorine is paratoluensulfonyl chloride Or to Methoxybenzenesulfonyl chloride.
3. preparation method according to claim 2, which is characterized in that using volume ratio is (5~10): 1 petroleum ether and second The mixture of acetoacetic ester carries out gradient elution to the thioetherification Benzazole compounds obtained after being stirred to react as mobile phase, obtains The thioetherification Benzazole compounds of solid.
4. preparation method according to claim 3, which is characterized in that the time being stirred to react passes through thin-layered chromatography It determines.
5. preparation method according to claim 1, which is characterized in that the substance of the catalyst and indoles reactant The ratio of amount is 1:10；Concentration of the indoles reactant in the solvent is 1~1.5mol/L.
6. the thioetherification Benzazole compounds that the preparation method as described in any one of Claims 1 to 5 obtains, feature exist In the general structure of the thioetherification Benzazole compounds are as follows:
Wherein, the R1For hydrogen, hydroxyl or methoxyl group；The R2For hydrogen, the R3For hydrogen, the R4For methyl or methoxy.
7. thioetherification Benzazole compounds according to claim 6, which is characterized in that the thioetherification Benzazole compounds For 4- hydroxyl -3- [(4- tolyl) sulfydryl]-indoles, structural formula is
The indoles reactant is 4- oxyindole, and the substituted phenyl sulfonyl chlorine is paratoluensulfonyl chloride.
8. thioetherification Benzazole compounds according to claim 6, which is characterized in that the thioetherification Benzazole compounds For 6- methoxyl group -3- [(4- tolyl) sulfydryl]-indoles, structural formula is
The indoles reactant is 6- methoxy-Indole, and the substituted phenyl sulfonyl chlorine is paratoluensulfonyl chloride.
9. thioetherification Benzazole compounds according to claim 6, which is characterized in that the thioetherification Benzazole compounds For 3- [(4- methoxyphenyl) sulfydryl]-indoles, structural formula is
The indoles reactant is indoles, and the substituted phenyl sulfonyl chlorine is to Methoxybenzenesulfonyl chloride.
10. application of the preparation method in sulfide synthesis Benzazole compounds as described in any one of Claims 1 to 5.
CN201710980427.6A 2017-10-19 2017-10-19 Thioetherification Benzazole compounds and preparation method thereof Pending CN109678784A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006060535A2 (en) * 2004-11-30 2006-06-08 Plexxikon, Inc. Indole derivatives for use as ppar active compounds
CN106608788A (en) * 2016-11-18 2017-05-03 东北师范大学 Preparation method of mild diazomethane derivative

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006060535A2 (en) * 2004-11-30 2006-06-08 Plexxikon, Inc. Indole derivatives for use as ppar active compounds
CN106608788A (en) * 2016-11-18 2017-05-03 东北师范大学 Preparation method of mild diazomethane derivative

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ANDREW G. MYERS,等: "Preparation of the Reagent o-Nitrobenzenesulfonylhydrazide", 《THE JOURNAL OF ORGANIC CHEMISTRY》 *
FU-LAI YANG,等: "Iodine-Catalyzed Regioselective Sulfenylation of Indoles with Sulfonyl Hydrazides", 《ANGEWANDTE CHEMIE, INTERNATIONAL EDITION》 *
SHIVANI SHARMA,等: "Microwave assisted metal-/oxidant-free cascade electrophilic sulfenylation/5-endo-dig cyclization of 2-alkynylanilines to generate diversified 3-sulfenylindoles", 《TETRAHEDRON LETTERS》 *
YU YANG,等: "Catalyst-free thiolation of indoles with sulfonyl hydrazides for the synthesis of 3-sulfenylindoles in water", 《GREEN CHEMISTRY》 *

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Application publication date: 20190426