CN111116466B - Catalytic synthesis method of polysubstituted quinoline derivative - Google Patents
Catalytic synthesis method of polysubstituted quinoline derivative Download PDFInfo
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- CN111116466B CN111116466B CN201911154685.4A CN201911154685A CN111116466B CN 111116466 B CN111116466 B CN 111116466B CN 201911154685 A CN201911154685 A CN 201911154685A CN 111116466 B CN111116466 B CN 111116466B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
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Abstract
The invention discloses a catalytic synthesis method of polysubstituted quinoline derivatives, which comprises the following steps: dissolving aryl propargyl substituted aniline in toluene at normal pressure, wherein the molar volume ratio of the aryl propargyl substituted aniline to the toluene is 1; adding zinc iodide into the toluene solution to obtain a mixed solution, wherein the molar amount of the zinc iodide is 10% of that of the aryl propargyl substituted aniline; and then heating the mixed solution to 100 ℃, stirring the mixed solution at constant temperature of 100 ℃ for 12 hours, and reacting to generate the polysubstituted quinoline derivative. The catalytic synthesis method of the polysubstituted quinoline derivative disclosed by the invention has the advantages of low cost and high yield, and the cost of the catalyst for preparing 1g of polysubstituted quinoline derivative is reduced by 3 orders of magnitude compared with the existing synthesis method using the rhodium complex as the catalyst, and the yield is improved to 90.5-96.2%.
Description
Technical Field
The invention relates to a synthesis method of a compound, in particular to a catalytic synthesis method of a polysubstituted quinoline derivative.
Background
Polysubstituted quinoline derivatives widely exist in natural products and medical molecules, and are receiving attention due to their excellent antimalarial, antiepileptic, antitumor and other activities. Quinoline derivatives are contained in very low amounts in plants and are currently mainly obtained by chemical synthesis. The traditional quinoline synthesis method is mainly obtained by reacting aniline with corresponding reagents under the condition of strong acid, and has the defects of violent reaction conditions and low yield. Although the yield of the method for synthesizing the polysubstituted quinoline derivative by using the noble metal catalyst is high, the preparation cost of the noble metal catalyst is high because the noble metal catalyst is expensive. Noble metal rhodium catalysts as reported in the literature can convert 2-ethynylaniline and benzaldehyde into the quinoline derivative 2-phenylquinoline at room temperature in 81% yield using acetone as a solvent. The cost of the catalyst per 1g of 2-phenylquinoline prepared is 700 yuan, depending on the market price of the rhodium catalyst.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a low-cost and high-yield catalytic synthesis method of polysubstituted quinoline derivatives aiming at the defects of the prior art, wherein the cost of the catalyst for preparing 1g of polysubstituted quinoline derivatives is reduced by 3 orders of magnitude compared with the cost of the conventional synthesis method using rhodium complexes as catalysts, and the yield is improved to 90.5-96.2%.
The technical scheme adopted by the invention for solving the technical problems is as follows: a catalytic synthesis method of polysubstituted quinoline derivatives comprises the following steps: dissolving aryl propargyl substituted aniline in toluene under normal pressure, wherein the molar volume ratio of the aryl propargyl substituted aniline to the toluene is 1; adding zinc iodide into the toluene solution to obtain a mixed solution, wherein the molar amount of the zinc iodide is 10% of that of the arylpropargyl substituted aniline; and then heating the mixed solution to 100 ℃, stirring at constant temperature of 100 ℃ for 12 hours, and reacting to generate the polysubstituted quinoline derivative.
Preferably, the stirring speed of stirring at constant temperature of 100 ℃ is 300 to 1000r/min.
Compared with the prior art, the invention has the following advantages: the invention discloses a catalytic synthesis method of polysubstituted quinoline derivatives, which is characterized in that the polysubstituted quinoline derivatives are synthesized by taking aryl propargyl substituted aniline as a raw material in a toluene solvent under normal pressure by using cheap zinc iodide as a catalyst, the synthesis method has low cost and high yield, the cost of the catalyst for preparing 1g of polysubstituted quinoline derivatives is reduced by 3 orders of magnitude compared with the existing synthesis method taking a rhodium complex as a catalyst, and the yield is improved to 90.5-96.2%.
Drawings
FIG. 1 is a NMR spectrum of 4-phenylquinoline derivative 2a prepared in example 1;
FIG. 2 is a NMR carbon spectrum of 4-phenylquinoline derivative 2a prepared in example 1.
Detailed Description
The invention is described in further detail below with reference to the following examples of the drawings.
Example 1: dissolving 10mmol of phenyl propargyl substituted aniline 1a in 10mL of toluene under normal pressure to obtain a toluene solution of phenyl propargyl substituted aniline 1 a; then adding 1.0mmol of zinc iodide into the toluene solution to obtain a mixed solution; then, the mixed solution was heated to 100 ℃ and stirred at a stirring rate of 600r/min at a constant temperature of 100 ℃ for 12 hours to react and produce 4-phenylquinoline derivative 2a, and the 4-phenylquinoline derivative 2a was obtained in an amount of 3.8g by silica gel column chromatography, showing a yield of 90.5%. In example 1, the reaction formula for synthesizing the 4-phenylquinoline derivative 2a using phenyl propargyl substituted aniline 1a as a raw material is as follows:
through calculation, in example 1, the cost of the catalyst required for preparing 1g of the 4-phenylquinoline derivative 2a is only 0.6 yuan, which is reduced by 3 orders of magnitude compared with the existing synthesis method using rhodium complex as the catalyst.
The NMR chart of 4-phenylquinoline derivative 2a prepared in example 1 is shown in FIG. 1, which contains specific data 1 H NMR(400MHz,CDCl 3 )δ7.37-7.30(m,2H),7.08-7.00(m,4H),6.90(d,J＝8.0Hz,2H),6.53-6.48(m,2H),6.25(d,J＝2.5Hz,1H),5.39(t,J＝5.0Hz,1H),4.35(d,J＝5.1Hz,2H),3.84(s,3H),3.23(s,3H),2.14(s,3H).
The NMR spectrum of 4-phenylquinoline derivative 2a prepared in example 1 is shown in FIG. 2, and specific data are shown in FIG. 2 13 C NMR(101MHz,CDCl 3 )δ160.06,157.01,143.34,140.74,138.96,137.24,136.47,129.13,127.44,126.91,126.43,126.23,120.10,113.51,103.48,98.58,55.69,55.20,45.62,21.33.
Example 2: 20mmol of tolylpropargyl-substituted aniline 1b were dissolved in 20mL of toluene under normal pressure to give a toluene solution of tolylpropargyl-substituted aniline 1 b; adding 2.0mmol of zinc iodide into the toluene solution to obtain a mixed solution; then, the mixed solution was heated to 100 ℃ and stirred at a stirring rate of 500r/min at a constant temperature of 100 ℃ for 12 hours to react and produce 4-tolylquinoline derivative 2b, and silica gel column chromatography was performed to give 8.3g of 4-tolylquinoline derivative 2b, with a yield of 95.3%.
The reaction formula for synthesizing the 4-tolylquinoline derivative 2b using tolylpropargyl-substituted aniline 1b as a starting material in example 2 is:
through calculation, in example 2, the cost of the catalyst required for preparing 1g of the 4-tolylquinoline derivative 2b is only 0.57 yuan, which is reduced by 3 orders of magnitude compared with the existing synthesis method using rhodium complex as the catalyst.
Example 3: dissolving 40mmol of methoxyphenyl propargyl substituted aniline 1c in 40mL of toluene under normal pressure to obtain a toluene solution of methoxyphenyl propargyl substituted aniline 1 c; adding 4.0mmol of zinc iodide into the toluene solution to obtain a mixed solution; then, the mixed solution was heated to 100 ℃ and stirred at a stirring rate of 800r/min at a constant temperature of 100 ℃ for 12 hours to react and produce 4-methoxyphenyl quinoline derivative 2c, and silica gel column chromatography was performed to obtain 16.5g of 4-methoxyphenyl quinoline derivative 2c, with a yield of 91.6%.
In example 3, the reaction formula for synthesizing the 4-methoxyphenyl quinoline derivative 2c by using methoxyphenyl propargyl substituted aniline 1c as a raw material is as follows:
through calculation, in example 3, the cost of the catalyst required for preparing 1g of the 4-methoxyphenyl quinoline derivative 2c is only 0.55 yuan, which is reduced by 3 orders of magnitude compared with the existing synthesis method using rhodium complex as the catalyst.
Example 4: dissolving 80mmol of chlorophenylpropargyl substituted aniline 1d in 80mL of toluene under normal pressure to obtain a toluene solution of the chlorophenylpropargyl substituted aniline 1 d; adding 8.0mmol of zinc iodide into the toluene solution to obtain a mixed solution; then, the mixed solution was heated to 100 ℃ and stirred at a stirring rate of 400r/min at a constant temperature of 100 ℃ for 12 hours to react and produce 4-chlorophenyl quinoline derivative 2d, and silica gel column chromatography was performed to obtain 35.1g of 4-chlorophenyl quinoline derivative 2d, with a yield of 96.2%. In example 4, the formula for synthesizing the 4-chlorophenyl quinoline derivative 2d using chlorophenyl propargyl substituted aniline 1d as a starting material is:
through calculation, in example 4, the cost of the catalyst required for preparing 1g of the 4-chlorophenyl quinoline derivative 2d is only 0.55 yuan, which is reduced by 3 orders of magnitude compared with the existing synthesis method using rhodium complex as the catalyst.
Example 5: dissolving 100mmol of bromophenylpropargyl-substituted aniline 1e in 100mL of toluene under normal pressure to obtain a toluene solution of bromophenylpropargyl-substituted aniline 1 e; then adding 10.0mmol of zinc iodide into the toluene solution to obtain a mixed solution; then, the mixed solution is heated to 100 ℃, stirred at the stirring speed of 1000r/min and the constant temperature of 100 ℃ for 12 hours, 4-bromophenyl quinoline derivative 2e is generated through reaction, and the 4-bromophenyl quinoline derivative 2e is obtained by silica gel column chromatography and is 46.3g, and the yield is 92.5%. In example 5, the reaction formula for synthesizing 4-bromophenylquinoline derivative 2e using bromophenylpropargyl-substituted aniline 1e as a raw material is as follows:
by calculation, in example 5, the cost of the catalyst required for preparing 1g of the 4-bromophenylquinoline derivative 2e is only 0.51 yuan, which is reduced by 3 orders of magnitude compared with the existing synthesis method using iridium catalyst as catalyst.
Claims (2)
1. The catalytic synthesis method of the polysubstituted quinoline derivative is characterized by comprising the following steps: dissolving aryl propargyl substituted aniline in toluene at normal pressure, wherein the molar volume ratio of the aryl propargyl substituted aniline to the toluene is 1; adding zinc iodide into the toluene solution to obtain a mixed solution, wherein the molar amount of the zinc iodide is 10% of that of the aryl propargyl substituted aniline; then, heating the mixed solution to 100 ℃, stirring at constant temperature of 100 ℃ for 12 hours, and reacting to generate a polysubstituted quinoline derivative; the aryl propargyl substituted aniline is phenyl propargyl substituted aniline, tolyl propargyl substituted aniline, methoxyphenyl propargyl substituted aniline, chlorophenyl propargyl substituted aniline or bromophenyl propargyl substituted aniline, and the chemical structural formulas are respectively
2. The catalytic synthesis method of polysubstituted quinoline derivatives according to claim 1, wherein the stirring rate at constant temperature of 100 ℃ is 300-1000 r/min.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107739333A (en) * | 2017-11-14 | 2018-02-27 | 大连理工大学 | A kind of preparation method of green quinoline compound |
| CN109651228A (en) * | 2019-01-07 | 2019-04-19 | 浙江万里学院 | A kind of process for catalytic synthesis of N- p-toluenesulfonyl -2- substituent indole compound |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107739333A (en) * | 2017-11-14 | 2018-02-27 | 大连理工大学 | A kind of preparation method of green quinoline compound |
| CN109651228A (en) * | 2019-01-07 | 2019-04-19 | 浙江万里学院 | A kind of process for catalytic synthesis of N- p-toluenesulfonyl -2- substituent indole compound |
Non-Patent Citations (2)
| Title |
|---|
| Metal Triflate-Catalyzed Regio- and Stereoselective Friedel–Crafts Alkenylation of Arenes with Alkynes in an Ionic Liquid: Scope and Mechanism;Mi Young Yoon，等;《Adv. Synth. Catal.》;20071231;1725-1737 * |
| Preparation of 3‑Iodoquinolines from N‑Tosyl-2-propynylamines with Diaryliodonium Triflate and N‑Iodosuccinimide;Teppei Sasaki，等;《J. Org. Chem.》;20170718;11727-11734 * |
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