CN109651228A - A kind of process for catalytic synthesis of N- p-toluenesulfonyl -2- substituent indole compound - Google Patents

A kind of process for catalytic synthesis of N- p-toluenesulfonyl -2- substituent indole compound Download PDF

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CN109651228A
CN109651228A CN201910010901.1A CN201910010901A CN109651228A CN 109651228 A CN109651228 A CN 109651228A CN 201910010901 A CN201910010901 A CN 201910010901A CN 109651228 A CN109651228 A CN 109651228A
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toluenesulfonyl
aniline
acetonitrile
indole compound
alkynyl substituted
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CN109651228B (en
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戎舟挺
钱国英
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Zhejiang Wanli College
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Zhejiang Wanli College
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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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Indole Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

The process for catalytic synthesis of N- p-toluenesulfonyl -2- substituent indole compound disclosed by the invention; it include: under normal temperature and pressure; the aniline of N- p-toluenesulfonyl -2- alkynyl substituted is dissolved in acetonitrile; the aniline of N- p-toluenesulfonyl -2- alkynyl substituted and the molal volume ratio of acetonitrile are 1:1mmol/mL, obtain the acetonitrile solution of the aniline of N- p-toluenesulfonyl -2- alkynyl substituted；The mole dosage of addition stannous chloride and cesium carbonate into acetonitrile solution again, stannous chloride and cesium carbonate is respectively the 5% of the aniline mole dosage of N- p-toluenesulfonyl -2- alkynyl substituted；Later, it is stirred at room temperature 6 hours, reaction generates N- p-toluenesulfonyl -2- substituent indole compound.The cost of the synthetic method is low, high income, and the cost of catalyst needed for preparing the N- p-toluenesulfonyl -2- substituent indole compound of 1g is more existing to reduce by 3 orders of magnitude by the synthetic method of catalyst of rhodium catalyst, and yield is improved to 89.1~97.0%.

Description

A kind of process for catalytic synthesis of N- p-toluenesulfonyl -2- substituent indole compound
Technical field
The present invention relates to a kind of synthetic method of compound, specifically a kind of N- p-toluenesulfonyl -2- substituent indole The process for catalytic synthesis of compound.
Background technique
2- substituent indole compound is widely present in natural products and pharmaceutical molecules, because its with good antibacterial, Anti-oxidant, antitumor isoreactivity and be concerned.Since 2- substituent indole compound can be replaced by N- p-toluenesulfonyl -2- Benzazole compounds take off p-toluenesulfonyl and obtain, therefore N- p-toluenesulfonyl -2- substituent indole compound becomes conjunction It is valuable chemical products at the important intermediate of 2- substituent indole compound.Currently, with N- p-toluenesulfonyl- The aniline of 2- alkynyl substituted is raw material, synthesizes N- p-toluenesulfonyl -2- substituent indole chemical combination by intramolecular cyclisation Object is more general preparation method, but needs in synthetic method using expensive noble metal catalyst or higher temperature more Degree, preparation cost is higher, and product yield is moderate.As dicarbonyl rhodium acetylacetonate catalyst reported in the literature and 2,2'- it is bis-- (diphenyl phosphine) -1,1'- dinaphthalene can be at 100 DEG C, using toluene and water as solvent, by N- p-toluenesulfonyl -2- (2- phenyl) Acetylenylaniline is converted into N- p-toluenesulfonyl -2-phenylindone, yield 75%.It is catalyzed according to dicarbonyl rhodium acetylacetonate Agent and 2,2'- is bis--market price of (diphenyl phosphine) -1,1'- dinaphthalene, every N- p-toluenesulfonyl -2-phenylindone for preparing 1g The cost of required catalyst is 100 yuan.
Summary of the invention
The technical problem to be solved by the present invention is in view of the deficiencies of the prior art, provide a kind of at low cost, high income The process for catalytic synthesis of N- p-toluenesulfonyl -2- substituent indole compound.
The technical scheme of the invention to solve the technical problem is: a kind of N- p-toluenesulfonyl -2- replaces Yin The process for catalytic synthesis of diindyl class compound, includes the following steps: under normal temperature and pressure, by N- p-toluenesulfonyl -2- alkynyl substituted Aniline be dissolved in acetonitrile, wherein the molal volume ratio of the aniline and acetonitrile of N- p-toluenesulfonyl -2- alkynyl substituted be 1: 1mmol/mL obtains the acetonitrile solution of the aniline of N- p-toluenesulfonyl -2- alkynyl substituted；Chlorination is added into acetonitrile solution again Cuprous and cesium carbonate, wherein the mole dosage of stannous chloride and cesium carbonate is respectively the N- p-toluenesulfonyl -2- alkynyl The 5% of substituted aniline mole dosage；Later, it is stirred at room temperature 6 hours, reaction generates N- p-toluenesulfonyl -2- substituted indole Class compound.
Preferably, the stirring rate being stirred at room temperature is 300~1000r/min.
Compared with prior art, the present invention has the advantage that N- p-toluenesulfonyl -2- disclosed by the invention replaces Yin The process for catalytic synthesis of diindyl class compound is at normal temperatures and pressures catalyst using cheap stannous chloride, in the carbon of catalytic amount Under sour caesium effect, in acetonitrile solvent, N- is obtained to first as Material synthesis using the aniline of N- p-toluenesulfonyl -2- alkynyl substituted Benzenesulfonyl -2- substituent indole compound, the cost of the synthetic method is low, high income, prepares the N- tolysulfonyl of 1g The cost of catalyst needed for base -2- substituent indole compound is more existing to reduce by 3 by the synthetic method of catalyst of rhodium catalyst A order of magnitude, yield are improved to 89.1~97.0%.
Detailed description of the invention
Fig. 1 is the N- p-toluenesulfonyl -2-phenylindone hydrogen nuclear magnetic resonance spectrogram prepared in embodiment 5；
Fig. 2 is the N- p-toluenesulfonyl -2-phenylindone carbon-13 nmr spectra figure prepared in embodiment 5.
Specific embodiment
The present invention will be described in further detail below with reference to the embodiments of the drawings.
Embodiment 1: under normal temperature and pressure, 10mmol N- p-toluenesulfonyl -2- (2- methyl) acetylenylaniline is dissolved in In 10mL acetonitrile, the acetonitrile solution of N- p-toluenesulfonyl -2- (2- methyl) acetylenylaniline is obtained；Add again into acetonitrile solution Enter 0.5mmol stannous chloride and 0.5mmol cesium carbonate；Later, it is stirred at room temperature 6 hours, is reacted with the stirring rate of 600r/min N- p-toluenesulfonyl -2 methyl indole is generated, obtains N- p-toluenesulfonyl -2 methyl indole 2.6g through silica gel column chromatography, Yield is 91.1%.It using N- p-toluenesulfonyl -2- (2- methyl) acetylenylaniline is Material synthesis N- to toluene in embodiment 1 Sulfonyl -2 methyl indole reaction equation are as follows:
Through calculating, in embodiment 1, every required catalyst of N- p-toluenesulfonyl -2 methyl indole for preparing 1g at This is only 0.2 yuan, more existing to reduce by 3 orders of magnitude by the synthetic method of catalyst of rhodium catalyst.
Embodiment 2: under normal temperature and pressure, 20mmol N- p-toluenesulfonyl -2- (2- ethyl) acetylenylaniline is dissolved in In 20mL acetonitrile, the acetonitrile solution of N- p-toluenesulfonyl -2- (2- ethyl) acetylenylaniline is obtained；Add again into acetonitrile solution Enter 1.0mmol stannous chloride and 1.0mmol cesium carbonate；Later, it is stirred at room temperature 6 hours, is reacted with the stirring rate of 700r/min N- p-toluenesulfonyl -2- ethylindole is generated, obtains N- p-toluenesulfonyl -2- ethylindole 5.6g through silica gel column chromatography, Yield is 93.5%.It using N- p-toluenesulfonyl -2- (2- ethyl) acetylenylaniline is Material synthesis N- to toluene in embodiment 2 The reaction equation of sulfonyl -2- ethylindole are as follows:
Through calculating, in embodiment 2, the required catalyst of every N- p-toluenesulfonyl -2- ethylindole for preparing 1g at This is only 0.19 yuan, more existing to reduce by 3 orders of magnitude by the synthetic method of catalyst of rhodium catalyst.
Embodiment 3: under normal temperature and pressure, 40mmol N- p-toluenesulfonyl -2- (2- butyl) acetylenylaniline is dissolved in In 40mL acetonitrile, the acetonitrile solution of N- p-toluenesulfonyl -2- (2- butyl) acetylenylaniline is obtained；Add again into acetonitrile solution Enter 2.0mmol stannous chloride and 2.0mmol cesium carbonate；Later, it is stirred at room temperature 6 hours, is reacted with the stirring rate of 500r/min N- p-toluenesulfonyl -2- indole-butyl is generated, obtains N- p-toluenesulfonyl -2- indole-butyl 12.4g through silica gel column chromatography, Yield is 94.7%.It using N- p-toluenesulfonyl -2- (2- butyl) acetylenylaniline is Material synthesis N- to toluene in embodiment 3 The reaction equation of sulfonyl -2- indole-butyl are as follows:
Through calculating, in embodiment 3, the required catalyst of every N- p-toluenesulfonyl -2- indole-butyl for preparing 1g at This is only 0.17 yuan, more existing to reduce by 3 orders of magnitude by the synthetic method of catalyst of rhodium catalyst.
Embodiment 4: under normal temperature and pressure, 80mmol N- p-toluenesulfonyl -2- (2- cyclopropyl) acetylenylaniline is dissolved in In 80mL acetonitrile, the acetonitrile solution of N- p-toluenesulfonyl -2- (2- cyclopropyl) acetylenylaniline is obtained；Again into acetonitrile solution 4.0mmol stannous chloride and 4.0mmol cesium carbonate is added；Later, 6 hours are stirred at room temperature with the stirring rate of 800r/min, instead Tosyl -2- cyclopropyl indoles should be generated, obtains tosyl -2- cyclopropyl indoles 22.2g through silica gel column chromatography, is received Rate is 89.1%.It using N- p-toluenesulfonyl -2- (2- cyclopropyl) acetylenylaniline is Material synthesis N- to toluene in embodiment 4 The reaction equation of sulfonyl -2- cyclopropyl indoles are as follows:
Through calculating, in embodiment 4, the required catalyst of every N- p-toluenesulfonyl -2- cyclopropyl indoles for preparing 1g Cost is only 0.19 yuan, more existing to reduce by 3 orders of magnitude by the synthetic method of catalyst of rhodium catalyst.
Embodiment 5: under normal temperature and pressure, 100mmol N- p-toluenesulfonyl -2- (2- phenyl) acetylenylaniline is dissolved in In 100mL acetonitrile, the acetonitrile solution of N- p-toluenesulfonyl -2- (2- phenyl) acetylenylaniline is obtained；Again into acetonitrile solution 5.0mmol stannous chloride and 5.0mmol cesium carbonate is added；Later, 6 hours are stirred at room temperature with the stirring rate of 900r/min, instead N- p-toluenesulfonyl -2-phenylindone should be generated, obtains N- p-toluenesulfonyl -2-phenylindone 33.7g through silica gel column chromatography, Its yield is 97.0%.It using N- p-toluenesulfonyl -2- (2- phenyl) acetylenylaniline is Material synthesis N- to first in embodiment 5 Benzenesulfonyl -2-phenylindone reaction equation are as follows:
Through calculating, in embodiment 5, the cost of catalyst needed for every N- p-toluenesulfonyl -2-phenylindone for preparing 1g It is only 0.2 yuan, more existing to reduce by 3 orders of magnitude by the synthetic method of catalyst of rhodium catalyst.
N- p-toluenesulfonyl -2-phenylindone the hydrogen nuclear magnetic resonance spectrogram prepared in embodiment 5 is shown in Fig. 1, specific Data are1H NMR(400MHz,CDCl3) δ 8.38 (d, J=8.4Hz, 1H), 7.57 (dd, J=7.2,2.5Hz, 2H), 7.53- 7.48 (m, 4H), 7.42 (ddd, J=8.5,7.2,1.4Hz, 1H), 7.36-7.30 (m, 3H), 7.10 (d, J=8.1Hz, 2H), 6.61(s,1H),2.35(s,3H).
N- p-toluenesulfonyl -2-phenylindone carbon-13 nmr spectra the figure prepared in embodiment 5 is shown in Fig. 2, specific Data are13C NMR(101MHz,CDCl3)δ144.50,142.14,138.30,134.73,132.43,130.55,130.34, 129.18,128.63,127.48,126.80,124.76,124.29,120.68,116.66,113.58,21.51。

Claims (2)

1. a kind of process for catalytic synthesis of N- p-toluenesulfonyl -2- substituent indole compound, which is characterized in that including as follows Step: under normal temperature and pressure, the aniline of N- p-toluenesulfonyl -2- alkynyl substituted is dissolved in acetonitrile, wherein N- tolysulfonyl The aniline of base -2- alkynyl substituted and the molal volume ratio of acetonitrile are 1:1mmol/mL, obtain N- p-toluenesulfonyl -2- alkynyl and take The acetonitrile solution of the aniline in generation；Stannous chloride and cesium carbonate is added into acetonitrile solution again, wherein stannous chloride and cesium carbonate Mole dosage is respectively the 5% of the aniline mole dosage of the N- p-toluenesulfonyl -2- alkynyl substituted；Later, it is stirred at room temperature 6 hours, reaction generated N- p-toluenesulfonyl -2- substituent indole compound.
2. a kind of process for catalytic synthesis of N- p-toluenesulfonyl -2- substituent indole compound according to claim 1, It is characterized in that, the stirring rate being stirred at room temperature is 300~1000r/min.
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Cited By (2)

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Publication number Priority date Publication date Assignee Title
CN111116466A (en) * 2019-11-22 2020-05-08 浙江万里学院 Catalytic synthesis method of polysubstituted quinoline derivative
CN111285792A (en) * 2020-03-23 2020-06-16 三峡大学 2-substituted indole compound and preparation method thereof

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111116466A (en) * 2019-11-22 2020-05-08 浙江万里学院 Catalytic synthesis method of polysubstituted quinoline derivative
CN111116466B (en) * 2019-11-22 2023-02-10 浙江万里学院 Catalytic synthesis method of polysubstituted quinoline derivative
CN111285792A (en) * 2020-03-23 2020-06-16 三峡大学 2-substituted indole compound and preparation method thereof
CN111285792B (en) * 2020-03-23 2023-05-02 三峡大学 2-substituted indole compound and preparation method thereof

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