CN110156675B - Synthesis method of quinoline compound containing sulfonyl - Google Patents
Synthesis method of quinoline compound containing sulfonyl Download PDFInfo
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- CN110156675B CN110156675B CN201910560700.9A CN201910560700A CN110156675B CN 110156675 B CN110156675 B CN 110156675B CN 201910560700 A CN201910560700 A CN 201910560700A CN 110156675 B CN110156675 B CN 110156675B
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- C07—ORGANIC CHEMISTRY
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- 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
- C07D215/12—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 substituted hydrocarbon radicals attached to ring carbon atoms
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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
- C07D215/18—Halogen atoms or nitro radicals
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Abstract
The invention provides a method for synthesizing a quinoline compound containing sulfonyl, which belongs to the field of organic synthesis, can complete reaction only under the action of a visible light catalyst without using a metal catalyst, and has the advantages of simple reaction system, no need of heating for the reaction and high reaction yield. The technical scheme comprises the steps of respectively adding quinoline compounds and sulfonyl chloride compounds into a reactor, and reacting for 4-12 hours at room temperature under the illumination condition of white LED (light-emitting diode) light under the action of a photocatalyst and acetone serving as a solvent; and after the reaction is finished, performing column chromatography separation to obtain the quinoline compound containing sulfonyl. The synthesis method provided by the invention provides an optimal alternative solution for efficiently synthesizing the quinoline compound containing the sulfonyl group.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a method for synthesizing a quinoline compound containing sulfonyl.
Background
The quinoline compounds containing sulfonyl group have various biological activities, have achieved satisfactory multifaceted effects in recent years, and are more and more valued by chemical researchers all over the world. Currently, a currently available preparation method of quinoline compounds containing sulfonyl groups is to react quinoline compounds with sodium benzenesulfonate in the presence of an iodine catalyst and an oxidant at a high temperature to obtain quinoline compounds (chem.
However, in the above preparation process, not only the catalyst is used in the reaction system, but also high temperature heating is required to make the environment unfriendly, the yield of the obtained product is not ideal, and the like. Therefore, the method provided at present is not economical and is not the optimal solution in experimental synthesis of the quinoline compounds containing sulfonyl groups.
Disclosure of Invention
The invention provides a method for synthesizing a quinoline compound containing sulfonyl, which can complete reaction only under the action of a visible light catalyst without using a metal catalyst, has a simple reaction system, does not need heating in the reaction, has high reaction yield and provides an optimal alternative solution for efficiently synthesizing the quinoline compound containing sulfonyl.
In order to achieve the above object, the present invention provides a method for synthesizing a quinoline compound containing a sulfonyl group, which is characterized by comprising the following steps:
respectively adding quinoline compounds and sulfonyl chloride compounds into a reactor, and reacting for 4-12 hours at room temperature under the illumination condition of white LED (light-emitting diode) light under the action of a photocatalyst and acetone serving as a solvent;
and after the reaction is finished, performing column chromatography separation to obtain the quinoline compound containing sulfonyl.
Preferably, the quinoline compound has the following structural formula (A):
wherein R is1Is selected from-CH3，R2Selected from-H, -Cl, -CH3Any one of, -F and-Br.
Preferably, the sulfonyl chloride compound is any one of benzene sulfonyl chloride, p-methyl benzene sulfonyl chloride or methyl sulfonyl chloride.
Preferably, the quinoline compound containing sulfonyl has the following structural formula (B):
wherein R is2Selected from-H, -Cl, -CH3Any one of-F and-Br, R3Any one selected from-H, phenyl and tolyl.
Preferably, the millimole ratio of the quinoline compound to the sulfonyl chloride compound is 1 (1-1.1).
Preferably, the photoinitiator is benzophenone.
Preferably, the millimolar ratio of benzophenone to quinoline compound added is 0.1: 1.
Preferably, the chromatographic column used in the column chromatography is a silica gel column, and the eluent used is a mixed solvent of ethyl acetate and petroleum ether, and the volume ratio of the ethyl acetate to the petroleum ether is 1:5-2: 1.
Compared with the prior art, the invention has the advantages and positive effects that:
the synthesis method provided by the invention takes quinoline compounds and sulfonyl chloride compounds as basic raw materials, and can complete the reaction only by using a visible-light-driven photocatalyst under the condition of no metal residue. The synthesis method has the advantages of simple reaction system, no need of heating for reaction, operation under room temperature condition and LED lamp illumination condition, high yield of the product obtained by the reaction, and providing an optimal alternative solution for efficiently synthesizing the quinoline compound containing sulfonyl.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The embodiment of the invention provides a method for synthesizing a quinoline compound, which comprises the following steps:
s1: respectively adding quinoline compounds and sulfonyl chloride compounds into a reactor, and reacting for 4-12 hours at room temperature under the illumination condition of white LED (light-emitting diode) light under the action of a photocatalyst and acetone serving as a solvent;
in the step, quinoline compounds and sulfonyl chloride compounds are utilized to synthesize quinoline compounds containing sulfonyl groups, specifically, benzophenone is excited under the condition of illumination to become oxygen free radicals, then hydrogen atoms at the benzyl position of the quinoline compounds are captured to generate carbon free radicals, and the carbon free radicals are reacted with the sulfonyl chloride to generate target products. It should be noted here that the reaction in this step does not need to be heated, and the reaction is performed at room temperature, and the amount of benzophenone which is preferable as the visible light catalyst is extremely low, and the reaction time is short; in addition, the method has good selectivity, and the product yield can reach 97%. In a preferred embodiment, the LED lamp used is 8W. It is understood that the reaction time set in this step is set according to the reaction temperature and the intensity of the lamp light, and those skilled in the art can adjust the reaction time according to the actual needs as long as the reaction is ensured to be sufficient.
S2: and after the reaction is finished, performing column chromatography separation to obtain the quinoline compound containing sulfonyl.
In a preferred embodiment, the quinoline compound has the following structural formula (A):
wherein R is1Is selected from-CH3，R2Selected from-H, -Cl, -CH3Any one of, -F and-Br.
In a preferred embodiment, the sulfonyl chloride compound is any one of benzene sulfonyl chloride, p-methyl benzene sulfonyl chloride or methyl sulfonyl chloride.
In a preferred embodiment, the quinoline compound containing sulfonyl group has the following structural formula (B):
wherein R is2Selected from-H, -Cl, -CH3Any one of-F and-Br, R3Any one selected from-H, phenyl and tolyl.
The specific structural formula of the sulfonyl group-containing quinoline compound used in the above embodiment is specifically defined, and it is understood that the sulfonyl group-containing quinoline compound defined in this embodiment uses quinoline as a parent nucleus, and a branched structure in a compound obtained from the sulfonyl group-containing quinoline compound is relatively simple, but the sulfonyl group-containing quinoline compound formed by a branched structure having a relatively complex structure is not excluded in this embodiment.
In a preferred embodiment, the millimole ratio of the quinoline compound to the sulfonyl chloride compound is 1 (1-1.1). In a preferred embodiment, the molar ratio of added benzophenone to added quinoline compound is 0.1: 1.
In the above examples, specific ratios of quinoline compound, sulfonyl chloride compound and benzophenone are given, wherein, in order to obtain the mother core structure of the expected compound accurately, the ratio of quinoline compound and sulfonyl chloride compound is set based on the requirement of reaction mechanism, the dosage of the catalyst is extremely low, and the addition amount of the solvent is relatively excessive to ensure sufficient reaction.
In a preferred embodiment, the chromatographic column used in the column chromatography is a silica gel column, and the eluent used is a mixed solvent of ethyl acetate and petroleum ether, and the volume ratio of the ethyl acetate to the petroleum ether is 1:5-2: 1. In this example, the product obtained by the reaction was subjected to gradient elution using a silica gel column to isolate the desired synthetic product. In this embodiment, gradient elution is performed by using a mixed solvent of ethyl acetate and petroleum ether in a volume ratio of 1:5 to 2:1, according to the principle of similar phase solubility and considering the polarity of the synthesized product, and within this range, the skilled person can adjust the gradient elution according to the actual situation.
In order to more clearly and specifically describe the synthesis method of the quinoline compound containing sulfonyl group provided in the embodiments of the present invention, the following description is given with reference to specific embodiments.
Example 1
Respectively adding into the reactor
1mmol, 1mmol of benzenesulfonyl chloride, 0.1mmol of benzophenone and 2ml of acetone, reacting for 4 hours at room temperature under the illumination condition of white 8W LED lamp, and performing column chromatography separation after the reaction is finished to obtain a target compound C1:
the white solid powder was subjected to nuclear magnetic spectrum analysis, and the data were as follows:
1H NMR(500MHz,CDCl3)δ8.06(d,J＝8.4Hz,1H),7.75(d,J＝8.5Hz,1H),7.71(d,J＝8.1Hz,1H),7.62–7.53(m,3H),7.46(t,J＝9.8Hz,3H),7.30(t,J＝7.8Hz,2H),4.67(s,2H)；
13C NMR(126MHz,CDCl3)δ149.25s,147.80,138.30,136.97,133.82,129.93,129.11,128.97,128.52,127.61,127.36,127.21,122.76,65.14；
after identification, the spectral data correspond to the structural formula, and the synthesized 2- ((phenylsulfonyl) methyl) quinoline is proved to be in 97% yield.
Example 2
Respectively adding into the reactor
1mmol, 1.1mmol of benzenesulfonyl chloride, 0.1mmol of benzophenone and 2ml of acetone, reacting for 6 hours at room temperature under the illumination condition of white 8W LED lamp, and performing column chromatography separation after the reaction is finished to obtain a target compound C2:
the white solid powder was subjected to nuclear magnetic spectrum analysis, and the data were as follows:
1H NMR(500MHz,CDCl3)δ8.04(d,J＝8.4Hz,1H),7.73(s,1H),7.65(d,J＝8.7Hz,1H),7.59(d,J＝7.9Hz,2H),7.49(dd,J＝15.2,7.9Hz,2H),7.39(d,J＝8.7Hz,1H),7.34(t,J＝7.6Hz,2H),4.63(s,2H)；
13C NMR(126MHz,CDCl3)δ150.44,148.13,138.20,136.72,135.76,133.96,129.05,128.85,128.47,128.26,128.18,125.68,122.96,65.12；
after identification, the spectral data correspond to the structural formula, which confirms that 7-chloro-2- (phenylsulfonyl) methyl) quinoline is synthesized with a yield of 92%.
Example 3
Respectively adding into the reactor
1mmol, 1.1mmol of benzenesulfonyl chloride, 0.1mmol of benzophenone and 2ml of acetone, reacting for 12 hours at room temperature under the illumination condition of white 8W LED lamp, and performing column chromatography separation after the reaction is finished to obtain a target compound C3:
the above yellow solid powder was subjected to nuclear magnetic spectrum analysis, and the data were as follows:
1H NMR(500MHz,CDCl3)δ8.08(d,J＝8.4Hz,1H),7.74(d,J＝8.6Hz,1H),7.68(d,J＝7.7Hz,2H),7.64–7.48(m,4H),7.42(t,J＝7.5Hz,2H),4.74(s,2H),2.54(s,3H).
13C NMR(126MHz,CDCl3)δ148.21,146.47,138.26,137.22,136.23,133.77,132.22,128.93,128.82,128.55,127.41,126.40,122.73,65.20,21.63；
after identification, the spectral data correspond to the structural formula, which proves that the synthesized quinoline is 6-methyl-2- ((phenylsulfonyl) methyl) quinoline with the yield of 91%.
Example 4
Respectively adding into the reactor
1mmol, 1mmol of p-toluenesulfonyl chloride, 0.1mmol of benzophenone and 2ml of acetone, reacting for 4 hours at room temperature under the illumination condition of white 8W LED lamp, and performing column chromatography separation after the reaction is finished to obtain a target compound C4:
the white solid powder was subjected to nuclear magnetic spectrum analysis, and the data were as follows:
1H NMR(500MHz,CDCl3)δ8.16(d,J＝8.3Hz,1H),7.88(d,J＝8.5Hz,1H),7.82(d,J＝8.1Hz,1H),7.68(t,J＝7.6Hz,1H),7.56(t,J＝9.5Hz,4H),7.21(d,J＝7.7Hz,2H),4.73(s,2H),2.39(s,3H)；
13C NMR(126MHz,CDCl3)δ149.40,147.87,144.83,136.87,135.46,129.85,129.62,129.20,128.52,127.61,127.37,127.14,122.75,65.32,21.63；
after identification, the spectral data correspond to the structural formula, which confirms that 2- (tosylmethyl) quinoline is synthesized with a yield of 95%.
Example 5
Respectively adding into the reactor
1mmol, 1mmol of p-toluenesulfonyl chloride, 0.1mmol of benzophenone and 2ml of acetone, reacting for 4 hours at room temperature under the illumination condition of white 8W LED lamp, and performing column chromatography separation after the reaction is finished to obtain a target compound C5:
the white solid powder was subjected to nuclear magnetic spectrum analysis, and the data were as follows:
1H NMR(500MHz,CDCl3)δ8.10(d,J＝8.4Hz,1H),7.98–7.79(m,1H),7.65–7.51(m,3H),7.44(t,J＝9.8Hz,2H),7.21(d,J＝7.7Hz,2H),4.70(s,2H),2.39(s,3H)；
13C NMR(126MHz,CDCl3)δ161.70,159.71,148.80(d,J＝2.8Hz),144.95(d,J＝12.9Hz),136.18(d,J＝5.5Hz),135.44,131.80(d,J＝9.2Hz),129.64,128.50,128.06(d,J＝10.1Hz),123.48,120.26,120.05,110.70,110.53,65.17,21.63；
after identification, the spectral data corresponded to the structural formula, demonstrating that 6-fluoro-2- (tosylmethyl) quinoline was synthesized in 96% yield.
Example 6
Respectively adding into the reactor
P-methylbenzenesulfonyl chloride1mmol, 0.1mmol of benzophenone and 2ml of acetone, reacting for 5 hours at room temperature under the illumination condition of white 8W LED lamp, and performing column chromatography separation after the reaction is finished to obtain a target compound C6:
the above yellow solid powder was subjected to nuclear magnetic spectrum analysis, and the data were as follows:
1H NMR(500MHz,CDCl3)δ8.06(d,J＝8.4Hz,1H),7.96(s,1H),7.73(s,2H),7.57(dd,J＝16.5,8.1Hz,3H),7.21(d,J＝7.7Hz,2H),4.70(s,2H),2.39(s,3H)；
13C NMR(126MHz,CDCl3)δ149.92,146.39,144.94,135.81,135.36,133.33,130.92,129.66,129.63,128.48,128.40,123.62,121.10,65.22,21.65；
after identification, the spectral data correspond to the structural formula, which proves that 6-bromo-2- (tosylmethyl) quinoline is synthesized with a yield of 96%.
Example 7
Respectively adding into the reactor
1mmol, 1mmol of methylsulfonyl chloride, 0.1mmol of benzophenone and 2ml of acetone, reacting for 5 hours at room temperature under the illumination condition of white 8W LED lamp, and performing column chromatography separation after the reaction is finished to obtain a target compound C7:
the white solid powder was subjected to nuclear magnetic spectrum analysis, and the data were as follows:
1H NMR(500MHz,DMSO)δ8.48(d,J＝8.4Hz,1H),8.15–8.00(m,2H),7.69(d,J＝8.6Hz,2H),4.89(s,2H),3.13(s,3H)；
13C NMR(126MHz,DMSO)δ152.70,148.03,137.57,135.06,130.45,128.14,127.83,126.15,124.36,62.39,41.23；
after identification, the spectral data corresponded to the structural formula, demonstrating that 7-chloro-2- ((methanesulfonyl) methyl) quinoline was synthesized in 93% yield.
Claims (4)
1. The method for synthesizing the quinoline compound containing the sulfonyl is characterized by comprising the following steps of:
respectively adding quinoline compounds and sulfonyl chloride compounds into a reactor, and reacting for 4-12 hours at room temperature under the illumination condition of white LED (light-emitting diode) light under the action of a photocatalyst benzophenone and a solvent acetone;
after the reaction is finished, carrying out column chromatographic separation to obtain a quinoline compound containing sulfonyl;
the structural formula of the quinoline compound is (A):
wherein R is1Is selected from-CH3，R2Selected from-H, -Cl, -CH3Any one of-F and-Br;
the sulfonyl chloride compound is any one of benzene sulfonyl chloride, p-methyl benzene sulfonyl chloride or methyl sulfonyl chloride;
the structural formula of the quinoline compound containing sulfonyl is (B):
wherein R is2Selected from-H, -Cl, -CH3Any one of-F and-Br, R3Any one selected from-H, phenyl and tolyl.
2. The synthesis method according to claim 1, wherein the millimolar ratio of the quinoline compound to the sulfonyl chloride compound is 1 (1-1.1).
3. The synthesis method according to claim 1, wherein the millimolar ratio of benzophenone to quinoline compound added is 0.1: 1.
4. The synthesis method according to claim 1, wherein the column used in the column chromatography is a silica gel column, and the eluent used is a mixed solvent of ethyl acetate and petroleum ether, and the volume ratio of the ethyl acetate to the petroleum ether is 1:5-2: 1.
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Non-Patent Citations (2)
| Title |
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| "Efficient 2-sulfolmethyl quinoline formation from 2-methylquinolines and sodium sulfinates under transition-metal free conditions";Xiao, Fuhong , et al.,;《Chemical Communications》;20141118;第51卷(第4期);652-654 * |
| "PREFERRED CARBON VS. NITROGEN SULFONYLATION ON β-CARBOLINES";L. Hazai, et al.;《SYNTHETIC COMMUNICATIONS》;20061109;第31卷(第6期);919-927 * |
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