CN113336749A - Preparation method of indoloquinoline compound - Google Patents
Preparation method of indoloquinoline compound Download PDFInfo
- Publication number
- CN113336749A CN113336749A CN202110572773.7A CN202110572773A CN113336749A CN 113336749 A CN113336749 A CN 113336749A CN 202110572773 A CN202110572773 A CN 202110572773A CN 113336749 A CN113336749 A CN 113336749A
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- CN
- China
- Prior art keywords
- compound
- indoloquinoline
- preparation
- reactor
- organic solvent
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- -1 indoloquinoline compound Chemical class 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 14
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 11
- 239000003960 organic solvent Substances 0.000 claims abstract description 11
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 8
- 239000011630 iodine Substances 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- KURPPWHPIYBYBS-UHFFFAOYSA-N 2-ethenylaniline Chemical compound NC1=CC=CC=C1C=C KURPPWHPIYBYBS-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000000126 substance Substances 0.000 claims abstract description 5
- CCMPERHWCIWLOI-UHFFFAOYSA-N 2-ethenyl-5-methylaniline Chemical compound CC1=CC=C(C=C)C(N)=C1 CCMPERHWCIWLOI-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000003814 drug Substances 0.000 claims abstract description 4
- 239000003973 paint Substances 0.000 claims abstract description 4
- 239000000575 pesticide Substances 0.000 claims abstract description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000004440 column chromatography Methods 0.000 claims description 4
- 239000012043 crude product Substances 0.000 claims description 4
- 239000012074 organic phase Substances 0.000 claims description 4
- 229920002545 silicone oil Polymers 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 239000000047 product Substances 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- MZXDPTWGJXNUMW-UHFFFAOYSA-N 7h-pyrido[3,2-c]carbazole Chemical class C1=CC=NC2=C3C4=CC=CC=C4NC3=CC=C21 MZXDPTWGJXNUMW-UHFFFAOYSA-N 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 238000003760 magnetic stirring Methods 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims 1
- 230000007613 environmental effect Effects 0.000 abstract description 3
- 238000010438 heat treatment Methods 0.000 abstract description 2
- 238000003756 stirring Methods 0.000 abstract description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000012625 DNA intercalator Substances 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention relates to a preparation method of an indoloquinoline compound, which comprises the steps of adding a compound I, a catalyst iodine simple substance, an organic solvent and a magneton into a reactor, placing the reactor into an oil bath kettle at 70-90 ℃, heating, stirring, reacting for 6-10 hours, terminating the reaction, and purifying the product to obtain the indoloquinoline compound; wherein the first compound is o-aminostyrene or 3-methyl-6-vinylaniline. The method has mild reaction conditions, high yield and environmental friendliness; has certain bioactivity, and can be used in the fields of medicine, pesticide and paint dye synthesis.
Description
Technical Field
The invention relates to the technical field of heterocyclic compound synthesis, in particular to a preparation method of an indoloquinoline compound.
Background
Indole-containing heterocyclic compounds are important chemical intermediates and products, and the compounds are widely found in a plurality of important natural products. In recent years, indoloquinoline compounds have received wide attention as DNA intercalators and excellent antimalarial properties. The roots of ivy are often used for malaria treatment because of the high amount of ivy (an indoloquinoline compound). However, the prior art does not have a reliable preparation method of the indoloquinoline compound.
Disclosure of Invention
The invention aims to provide a preparation method of an indoloquinoline compound, which has simple process, mild reaction and environmental protection.
The scheme adopted by the invention is as follows:
adding a compound I, a catalyst iodine simple substance, an organic solvent and a magneton into a reactor, placing the reactor into an oil bath kettle at 70-90 ℃, heating, stirring, reacting for 6-10 hours, terminating the reaction, and purifying the product to obtain the indoloquinoline compound; the reaction formula is as follows:
the first compound is o-aminostyrene or 3-methyl-6-vinylaniline.
Preferably, the dosage ratio of the compound I, the elementary iodine and the organic solvent is (0.2-10) mmol: (0.1-5) mmol: (2-50) ml.
Preferably, the organic solvent is dimethylsulfoxide solution.
Preferably, the bottom end of the reactor is immersed in a silicone oil bath, the height of the silicone oil being higher than the liquid level in the reactor.
Preferably, the purity of the iodine is not lower than 99.5%; the purity of the organic solvent is not less than 99.5%.
Preferably, the rotation speed of the magnetic stirring is 100-600 r/s.
Preferably, it is characterized in that the way of terminating the reaction is by adding water.
Preferably, the purification mode is extraction by using an organic solvent, the obtained organic phases are combined, a crude product is obtained by reduced pressure distillation, and the indoloquinoline compound is obtained by column chromatography separation and purification.
The invention also aims to provide an indoloquinoline compound prepared by the method.
The invention also aims to provide application of the indoloquinoline compound in the fields of medicine synthesis, pesticide synthesis and paint dye synthesis.
The invention uses the iodine simple substance as the catalyst, and bimolecular o-aminostyrene directly reacts to generate the required indoloquinoline compound, thereby ensuring the green, high-efficiency and high atom economy of the reaction. Mild reaction conditions, high selectivity, high yield and environmental protection. The synthesized indoloquinoline compound has certain bioactivity and can be applied to the fields of medicine synthesis, pesticide synthesis, paint dye synthesis and the like.
Detailed Description
The following examples are provided to further illustrate the present invention for better understanding, but the present invention is not limited to the following examples.
Example 1 preparation of 11-methyl-6-H-indole [2,3-b ] quinoline:
0.2mmol of o-aminostyrene and 50 mol% of catalyst I are added22mL of dimethyl sulfoxide solution and magneton. The reactor was placed in an oil bath at 70-90 ℃ for 8 hours. Pouring the reaction solution into a separating funnel, adding 15mL of distilled water, extracting for 3 times by using 10mL of ethyl acetate, combining the obtained organic phases, performing spin-drying by using a rotary evaporator, and separating and purifying the crude product by using column chromatography to obtain the 11-methyl-6-H-indole [2,3-b ]]Quinoline 18.8mg, as a yellow solid, yield 72%.
By hydrogen nuclear magnetic resonance1H NMR(400MHz,CDCl3):δ3.23(s,3H),7.29-7.33(m,1H),7.52-7.55(m,3H),7.75-7.79(m,1H),8.16(d,J＝8.93Hz,1H),8.27-8.30(m,2H),10.82(s,1H)；13C NMR(100MHz,CDCl3):δ15.3,110.8,117.1,120.1,122.0,122.8,123.7,124.2,124.2,127.2,127.5,128.8,139.6,141.1,146.1,152.9。
Example 2 preparation of 3,8, 11-trimethyl-6-H-indol [2,3-b ] quinoline
Adding 0.2mmol 3-methyl-6-vinyl aniline and 50 mol% of catalyst I22mL of dimethyl sulfoxide solution andone for magneton number 5. The reactor was placed in an oil bath at 70-90 ℃ for 8 hours. Pouring the reaction solution into a separating funnel, adding 15mL of distilled water, extracting for 3 times by using 10mL of ethyl acetate, combining the obtained organic phases, drying by a rotary evaporator, and separating and purifying the crude product by column chromatography to obtain the 3,8, 11-trimethyl-6-H-indole [2,3-b ]]Quinoline 16.9mg, as a yellow solid, 65% yield.
By hydrogen nuclear magnetic resonance1H NMR(400MHz,(CD3)2SO):δ2.49(s,3H),2.54(s,3H),3.11(s,3H),7.08(dd,J＝7.96Hz,J＝0.58Hz,1H),7.26(s,1H),7.32(dd,J＝8.61Hz,J＝1.65Hz,1H),7.72(s,1H),8.17(dd,J＝18.29Hz,J＝8.30Hz,2H),11.55(s,1H)；13C NMR(100MHz,(CD3)2SO):δ15.26,21.8,22.2,111.3,115.9,119.3,121.3,122.1,123.6,124.5,125.0,127.0,137.5,138.0,138.3,142.0,146.7,153.1.
While the foregoing is directed to the preferred embodiment of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow.
Claims (10)
1. The preparation method of the indoloquinoline compound is characterized in that a compound I, a catalyst iodine simple substance, an organic solvent and a magneton are added into a reactor, the reactor is placed in an oil bath kettle at 70-90 ℃ to be heated and stirred for reaction for 6-10 hours, the reaction is terminated, and the product is purified to obtain the indoloquinoline compound; the reaction formula is as follows:
the first compound is o-aminostyrene or 3-methyl-6-vinylaniline.
2. The preparation method according to claim 1, wherein the ratio of the first compound, the elemental iodine and the organic solvent is (0.2-10) mmol: (0.1-5) mmol: (2-50) ml.
3. The method according to claim 1, wherein the organic solvent is a dimethylsulfoxide solution.
4. The method according to claim 1, wherein the bottom end of the reactor is immersed in a silicone oil bath, and the height of the silicone oil is higher than the liquid level in the reactor.
5. The preparation method according to claim 1, wherein the purity of the iodine is not less than 99.5%; the purity of the organic solvent is not less than 99.5%.
6. The method of claim 1, wherein: the magnetic stirring speed is 100-600 rpm.
7. The process according to claim 1, wherein the reaction is terminated by adding water.
8. The preparation method according to claim 1, wherein the purification method comprises extracting with an organic solvent, combining the obtained organic phases, distilling under reduced pressure to obtain a crude product, and separating and purifying by column chromatography to obtain the indoloquinoline compounds.
9. An indoloquinoline compound characterized by being prepared by the method according to any one of claims 1 to 8.
10. The use of the indoloquinoline compound of claim 9 in the fields of drug synthesis, pesticide synthesis, and paint dye synthesis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110572773.7A CN113336749B (en) | 2021-05-25 | 2021-05-25 | Preparation method of indoloquinoline compound |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110572773.7A CN113336749B (en) | 2021-05-25 | 2021-05-25 | Preparation method of indoloquinoline compound |
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| Publication Number | Publication Date |
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| CN113336749A true CN113336749A (en) | 2021-09-03 |
| CN113336749B CN113336749B (en) | 2022-04-29 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114232013A (en) * | 2021-11-12 | 2022-03-25 | 华南理工大学 | Method for synthesizing indoloquinoline compound under electrochemical condition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103497211A (en) * | 2013-10-15 | 2014-01-08 | 中国海洋大学 | Indoloquinoline derivative and preparation method and application thereof |
-
2021
- 2021-05-25 CN CN202110572773.7A patent/CN113336749B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103497211A (en) * | 2013-10-15 | 2014-01-08 | 中国海洋大学 | Indoloquinoline derivative and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| KAZUHIRO KOBAYASHI ET AL.: "1H-indole Derivatives by Iodine-Mediated Cyclization of 2-(Arylamino)styrene Derivatives", 《BULL. CHEM. SOC. JPN.》 * |
| SHAUKAT ALI ET AL.: "One-Pot Access to Indolo[2,3-b]quinolines by Electrophile-Triggered Cross-Amination/Friedel−Crafts Alkylation of Indoles with 1-(2-Tosylaminophenyl)ketones", 《THE JOURNAL OF ORGANIC CHEMISTRY》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114232013A (en) * | 2021-11-12 | 2022-03-25 | 华南理工大学 | Method for synthesizing indoloquinoline compound under electrochemical condition |
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| CN113336749B (en) | 2022-04-29 |
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Effective date of registration: 20240823 Address after: 430073 No. 666, Gaoxin Avenue, East Lake Development Zone, Wuhan, Hubei Province Patentee after: WUHAN INNERSE PHARMACEUTICAL Inc. Country or region after: China Address before: 430068 No. 28 Nanli Road, Hongshan District, Wuhan City, Hubei Province Patentee before: HUBEI University OF TECHNOLOGY Country or region before: China |
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