CN113387883A

CN113387883A - Catalytic synthesis method of 8-substituted quinoline compound

Info

Publication number: CN113387883A
Application number: CN202110728659.9A
Authority: CN
Inventors: 胡伟灿; 戚天杭; 王超洋; 戎舟挺
Original assignee: Zhejiang Wanli University
Current assignee: Zhejiang Wanli University
Priority date: 2021-06-29
Filing date: 2021-06-29
Publication date: 2021-09-14

Abstract

The invention discloses a catalytic synthesis method of an 8-substituted quinoline compound, which comprises the following steps: dissolving corresponding acetylene amine derivatives and quinoline-N-oxide in dichloromethane at normal temperature and normal pressure, wherein the molar volume ratio of the acetylene amine derivatives to the dichloromethane is 1:5 mmol/mL, and the molar ratio of the acetylene amine derivatives to the quinoline-N-oxide is 1: 2, obtaining a dichloromethane solution of reactants; adding bis (trifluoromethane) sulfonyl imide into the dichloromethane solution, wherein the molar usage of the bis (trifluoromethane) sulfonyl imide is 5% of the molar usage of the acetylene amine derivative respectively; then, the mixture was stirred at room temperature for 1 hour to react to produce an 8-substituted quinoline compound. The catalytic synthesis method of the 8-substituted quinoline compound does not need to use expensive and highly toxic precious metal complexes as catalysts, so that the method is low in cost, low in toxicity, free of metal residues, mild in reaction conditions, high in reaction speed and high in yield of 84.1-98.4%.

Description

Catalytic synthesis method of 8-substituted quinoline compound

Technical Field

The invention relates to a synthesis method of a compound, in particular to a catalytic synthesis method of an 8-substituted quinoline compound.

Background

The 8-substituted quinoline is an important heterocyclic compound, widely exists in natural products and medicines, and has important application in the fields of medicine, agricultural production, functional materials and organic synthesis. Therefore, the development of a practical and efficient method for synthesizing the 8-substituted quinoline compound has important practical significance and application value.

The existing synthesis method of 8-substituted quinoline is mainly realized by noble metal catalytic reaction, but the methods are greatly limited in practical application due to the problems of expensive noble metal catalyst, high toxicity, high reaction temperature, easy metal residue during separation and purification and the like. quinoline-N-oxide and ethyl acrylate as reported in the literature react for 12 hours at 100 ℃ under the catalysis of a noble metal rhodium complex by using copper acetate monohydrate and acetic acid as additives and 1, 2-dichloroethane as a solvent to generate 8-substituted quinoline with the yield of 74%.

Disclosure of Invention

The invention aims to solve the technical problem of providing a catalytic synthesis method of an 8-substituted quinoline compound, which has low cost, low toxicity, mild reaction conditions and no metal residue, aiming at the defects of the prior art.

The technical scheme adopted by the invention for solving the technical problems is as follows: a catalytic synthesis method of 8-substituted quinoline compounds comprises the following steps: dissolving an acetylenylamine derivative and a quinoline-N-oxide in dichloromethane at normal temperature and normal pressure, wherein the molar volume ratio of the acetylenylamine derivative to the dichloromethane is 1:5 mmol/mL, and the molar ratio of the acetylenylamine derivative to the quinoline-N-oxide is 1: 2, obtaining a dichloromethane solution of reactants; adding bis (trifluoromethane) sulfonyl imide into the dichloromethane solution, wherein the molar amount of the bis (trifluoromethane) sulfonyl imide is 5% of that of the acetylene amine derivative; and then stirring at room temperature for 1 hour, reacting for 20 minutes or 40 minutes, obtaining a lower yield, wherein the yield tends to be stable after more than 1 hour, and stirring and collecting for 1 hour is an optimal time point, so that the method is more energy-saving, environment-friendly, economical and practical in process. The 8-substituted quinoline compound is generated by reaction. The reaction equation is as follows:

。

wherein the acetenylamine derivative has a structure shown in a formula I, and the quinoline-N-oxide has a structure shown in a formula IIIII is 8-substituted quinoline generated by the reaction. In the formulae I, II and III, R₁Selected from the group consisting of methanesulfonyl, p-toluenesulfonyl, o-nitrobenzenesulfonyl, benzoyl, tert-butoxycarbonyl, R₂Selected from methyl, ethyl, propyl, allyl, benzyl, p-methylbenzyl, p-methoxybenzyl, p-chlorobenzyl, R₃Selected from hydrogen atom, chlorine atom, methyl and methoxyl.

Preferably, the stirring speed of the room-temperature stirring is 100-1000 r/min, the rotating speed is lower than 100 r/min or higher than 1000r/mi, and the yield is greatly reduced.

Compared with the prior art, the invention has the following advantages: the invention discloses a catalytic synthesis method of 8-substituted quinoline compounds, which is characterized in that cheap bis (trifluoromethane) sulfonyl imide is used as a catalyst at normal temperature and normal pressure to catalyze reaction of an acetylenylamine derivative and quinoline-N-oxide in a dichloromethane solvent to obtain the 8-substituted quinoline compounds, and the synthesis method does not need to use expensive and highly toxic noble metal complexes as the catalyst, so that the cost is low, the toxicity is low, no metal residue is generated, the reaction condition is mild, the reaction speed is high, and the yield can reach 84.1-98.4%.

Drawings

FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of Compound A prepared in example 1;

FIG. 2 is a NMR carbon spectrum of Compound A prepared in example 1.

Detailed Description

The invention is described in further detail below with reference to the accompanying examples.

A catalytic synthesis method of 8-substituted quinoline compounds comprises the following steps: dissolving an acetylenylamine derivative and a quinoline-N-oxide in dichloromethane at normal temperature and normal pressure, wherein the molar volume ratio of the acetylenylamine derivative to the dichloromethane is 1:5 mmol/mL, and the molar ratio of the acetylenylamine derivative to the quinoline-N-oxide is 1: 2, obtaining a dichloromethane solution of reactants; adding bis (trifluoromethane) sulfonyl imide into the dichloromethane solution, wherein the molar usage of the bis (trifluoromethane) sulfonyl imide is 5% of the molar usage of the acetylene amine derivative respectively; then stirring for 1 hour at room temperature to react to generate 8-substituted quinoline compounds; the reaction equation is as follows:

，

wherein, the acetenylamine derivative has a structure shown in a formula I, the quinoline-N-oxide has a structure shown in a formula II, and the formula III is 8-substituted quinoline generated by reaction; in the formulae I, II and III, R₁Selected from the group consisting of methanesulfonyl, p-toluenesulfonyl, o-nitrobenzenesulfonyl, benzoyl, tert-butoxycarbonyl, R₂Selected from methyl, ethyl, propyl, allyl, benzyl, p-methylbenzyl, p-methoxybenzyl, p-chlorobenzyl, R₃Selected from hydrogen atom, chlorine atom, methyl and methoxyl.

The stirring speed of the room-temperature stirring is 100-1000 r/min.

Example 1: dissolving 1 mmol of substrate 1 and 2 mmol of quinoline-N-oxide in 5 mL of dichloromethane at normal temperature and normal pressure to obtain a dichloromethane solution of a reactant; then adding 0.05 mmol of bis (trifluoromethanesulfonimide) into the dichloromethane solution; then, the mixture was stirred at a stirring rate of 100 r/min at room temperature for 1 hour to react and produce Compound A, and the yield thereof was 98.4% by silica gel column chromatography to obtain 261.6 mg of Compound A. The reaction formula for synthesizing compound a in example 1 using substrate 1 as a starting material is:

。

example 2: dissolving 5 mmol of substrate 2 and 10 mmol of quinoline-N-oxide in 25 mL of dichloromethane at normal temperature and normal pressure to obtain a dichloromethane solution of reactants; then adding 0.25 mmol of bis (trifluoromethanesulfonyl) imide into the dichloromethane solution; then, the mixture was stirred at a stirring rate of 300 r/min at room temperature for 1 hour to react and produce compound B, and 1.6 g of compound B was obtained by silica gel column chromatography, and the yield thereof was 84.1%. The reaction formula for synthesizing compound B in example 2 using substrate 2 as a starting material is:

。

example 3: dissolving 10 mmol of

substrate

3 and 20 mmol of quinoline-N-oxide in 50 mL of dichloromethane at normal temperature and normal pressure to obtain a dichloromethane solution of reactants; then adding 0.5 mmol of bis (trifluoromethanesulfonyl) imide into the dichloromethane solution; then, the mixture was stirred at a stirring rate of 500 r/min at room temperature for 1 hour to react and produce compound C, and 3.6 g of compound C was obtained by silica gel column chromatography, and the yield thereof was 88.0%. The reaction formula for synthesizing compound C in example 3 using substrate 3 as a starting material is:

。

example 4: dissolving 15 mmol of substrate 4 and 30 mmol of quinoline-N-oxide in 75 mL of dichloromethane at normal temperature and normal pressure to obtain a dichloromethane solution of a reactant; then adding 0.75 mmol of bis (trifluoromethanesulfonyl) imide into the dichloromethane solution; then, the mixture was stirred at a stirring rate of 700 r/min at room temperature for 1 hour to react and produce a compound D, and the compound D4.5 g was obtained by silica gel column chromatography, whereby the yield was 92.0%. The reaction formula for synthesizing compound D in example 4 using substrate 4 as a starting material is:

。

example 5: dissolving 20 mmol of substrate 5 and 40 mmol of quinoline-N-oxide in 100 mL of dichloromethane at normal temperature and normal pressure to obtain a dichloromethane solution of reactants; then adding 1 mmol of bis (trifluoromethanesulfonyl) imide into the dichloromethane solution; then, the mixture was stirred at 1000r/min at room temperature for 1 hour to give a compound E, and the compound E6.7 g was obtained by silica gel column chromatography, showing a yield of 94.1%. The reaction formula for synthesizing compound E in example 5 using substrate 5 as a starting material is:

。

prepared as in example 1The NMR spectrum of the 8-substituted quinoline A is shown in FIG. 1, and specific data are shown in the figure¹H NMR (400 MHz, CDCl₃) δ 8.85 – 8.77 (m, 1H), 8.16 (dt, J = 8.2, 1.3 Hz, 1H), 7.79 (dd, J = 8.2, 1.4 Hz, 1H), 7.66 (d, J = 7.0 Hz, 1H), 7.53 (dd, J = 8.2, 7.0 Hz, 1H), 7.41 (ddd, J = 8.3, 4.2, 0.9 Hz, 1H), 4.54 (s, 2H), 3.46 (d, J = 1.0 Hz, 3H), 3.40 (d, J = 0.9 Hz, 3H)。

The NMR spectrum of the 8-substituted quinoline A prepared in example 1 is shown in FIG. 2, and specific data are shown in the figure¹³C NMR (101 MHz, CDCl₃) δ 172.92, 149.43, 146.31, 136.49, 133.33, 130.87, 128.42, 127.68, 126.48, 121.30, 41.24, 39.20, 32.87。

Claims

1. A catalytic synthesis method of 8-substituted quinoline compounds is characterized by comprising the following steps: dissolving an acetylenylamine derivative and a quinoline-N-oxide in dichloromethane at normal temperature and normal pressure, wherein the molar volume ratio of the acetylenylamine derivative to the dichloromethane is 1:5 mmol/mL, and the molar ratio of the acetylenylamine derivative to the quinoline-N-oxide is 1: 2, obtaining a dichloromethane solution of reactants; adding bis (trifluoromethane) sulfonyl imide into the dichloromethane solution, wherein the molar usage of the bis (trifluoromethane) sulfonyl imide is 5% of the molar usage of the acetylene amine derivative respectively; then stirring for 1 hour at room temperature to react to generate 8-substituted quinoline compounds; the reaction equation is as follows:

2. The catalytic synthesis method of 8-substituted quinoline compounds according to claim 1, wherein the stirring rate of stirring at room temperature is 100-1000 r/min.