CN111978249B - Preparation method of 3-sulfonyl quinoline compound - Google Patents
Preparation method of 3-sulfonyl quinoline compound Download PDFInfo
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Abstract
The invention relates to the technical field of organic synthesis, in particular to a preparation method of a 3-sulfonyl quinoline compound. Diiodine pentoxide is used as an initiator, tert-butyl peroxide is used as an oxidant, and an alkynyl imine compound and a sulfonyl hydrazine compound are mixed to carry out cyclization reaction to obtain the 3-sulfonyl quinoline compound. The preparation method of the 3-sulfonyl quinoline compound has the characteristics of easy operation, simple and convenient post-treatment, strong substrate designability and the like, can design and synthesize the compound with the required structure according to actual needs, and has strong practicability. Meanwhile, the compound prepared by the method has good physiological activity, can be used as a raw material to synthesize a series of heterocyclic compounds, and has higher economic value.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of a 3-sulfonyl quinoline compound.
Background
The quinoline compound is an important intermediate for organic synthesis, is one of common structural units in natural products, has multiple important physiological activities, and has great development and application value in the fields of biotechnology, medicine and pesticide development (document I: metal-free domino one-pot protocols for quinoline synthesis, J.B.Bharate, R.A.Vishwakarma and S.B.Bharate, RSC adv.2015, 42020-42053; document II: cu-catalyzed deoxygenative C2-sulfonylation reaction of quinoline N-oxides with sodium sulfinate, B.Du, P.Qian, Y.Wang, H.Mei, J.Han, Y.Pan, org.Lett.2016,18, 4144-4147). The preparation method of the 3-sulfonyl quinoline compounds is less reported in literature.
At present, a known method for synthesizing 3-sulfonyl quinoline compounds is to directly oxidize 3-mercapto quinoline compounds by using strong oxidants (such as m-chloroperoxybenzoic acid, hydrogen peroxide and the like), and the method is as follows:
the method needs strong oxidant, can generate equivalent by-products such as salt, is not suitable for industrial large-scale application, and also has a great pressure on environmental protection. Therefore, a method for preparing 3-sulfonyl quinoline compounds in an environment-friendly and efficient manner is needed.
Disclosure of Invention
Aiming at the defects existing in the prior art, the invention aims to provide a preparation method of 3-sulfonyl quinoline compounds. The preparation method utilizes a one-pot method, has higher atomic economy, meets the requirement of green chemistry, is easy to operate and realize industrialization, and the compound prepared by the method has simple preparation process, low cost and higher economic value.
The technical scheme adopted by the invention for achieving the purpose is as follows: a preparation method of 3-sulfonyl quinoline compounds uses diiodide as an initiator and tert-butyl peroxide as an oxidant, and takes cyclization reaction by mixing an alkynyl imine compound with a sulfonyl hydrazine compound to obtain the 3-sulfonyl quinoline compounds.
Further, the structure of the 3-sulfonyl quinoline compound is shown as a formula I; the structure of the alkynyl imine compound is shown as a formula II: the structure of the sulfonyl hydrazide compound is shown as a formula III:
wherein:
R 1 one selected from hydrogen, halogen or C1-C5 alkyl;
R 2 one selected from aryl, heteroaryl or C1-C5 alkyl;
R 3 one selected from aryl, C1-C5 alkyl or hydrogen;
R 4 selected from one of aryl or heteroaryl.
Further, said R 1 One selected from hydrogen, p-chloro or p-methyl;
said R is 2 One selected from phenyl, thienyl or cyclopropyl;
said R is 3 One selected from phenyl, tert-butyl or hydrogen;
said R is 4 Selected from one of phenyl or thienyl.
Further, the preparation method comprises the following steps:
(1) At a certain temperature, adding an alkynyl imine compound, a sulfonyl hydrazine compound and an organic solvent into a test tube reactor, and then adding diiodide pentoxide and tert-butyl peroxide, stirring to promote the reaction;
(2) After the reaction was completed, the reaction was quenched with saturated aqueous ammonium chloride solution, the organic phase was separated, the aqueous phase was extracted three times with diethyl ether, the organic phases were combined, dried over anhydrous sodium sulfate, desolventized, and purified with petroleum ether: eluting with ethyl acetate=3:1, and performing column chromatography to obtain white solid, namely the target product.
Further, the organic solvent is one of tetrahydrofuran, acetonitrile or 1, 2-dichloroethane.
Further, the alkynylimine compounds: sulfonyl hydrazide compound: diiodo pentoxide: the molar ratio of the tert-butyl peroxy alcohol is 1:1.2-1.5:1:2.5-3.0.
Further, the reaction temperature is 60-80 ℃ and the reaction time is 8-12 hours.
Further, the preparation method specifically comprises the following steps:
taking a 25mL test tube reactor, adding 0.5mmol of alkynyl imine, 0.6mmol of sulfonyl hydrazine and 5mL of acetonitrile, adding 0.5mmol of diiodine pentoxide and 2.5mmol of tert-butyl peroxide into the reaction system, and stirring for 8 hours; the progress of the reaction was checked by TLC for petroleum ether: ethyl acetate=3:1; after the reaction was completed, the reaction was quenched with 20mL of saturated aqueous ammonium chloride solution, the organic phase was separated, the aqueous phase was extracted three times with 50mL of diethyl ether each time, the organic phases were combined, dried over anhydrous sodium sulfate, desolventized, and petroleum ether was used: eluting with ethyl acetate=3:1, and performing column chromatography to obtain white solid, namely the target product.
Further, the reaction mechanism of the preparation reaction is as follows:
firstly, diiodide is a free radical initiator, the positive pentavalent iodine in diiodide has strong oxidizing property, and simultaneously, under the action of diiodide, sulfonyl hydrazine releases a molecule of nitrogen to generate sulfonyl free radicals in one step due to the existence of peroxy-tert-butyl alcohol, and diiodide is reduced into iodine simple substance;
then, the sulfonyl radical attacks the alkyne bond of the alkynyl imine compound and carries out cyclization reaction to obtain a cyclic intermediate; after the intermediate passes through a single electron transfer process, under the condition of water participation, the 3-sulfonyl quinoline compound is finally obtained.
The preparation method of the 3-sulfonyl quinoline compound has the beneficial effects that:
the compound provided by the invention is prepared by a one-pot method, is easy to operate, simple and convenient in post-treatment, and strong in substrate designability, and can be designed and synthesized into a compound with a required structure according to actual needs, so that the practicability is high. Meanwhile, the compound prepared by the method can be used as an important raw material for synthesizing some heterocyclic compounds, and has higher economic value. Has higher atomic economy, meets the requirement of green chemistry and is easy to realize industrialization. In addition, the invention also provides the compound prepared by the method, which has simple preparation process, low cost and higher economic value.
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FIG. 1 is a schematic flow chart of a reaction mechanism of an embodiment of the invention.
Detailed Description
The invention will be described in further detail with reference to the accompanying drawings and specific examples;
example 1:
a preparation method of 3-sulfonyl quinoline compounds uses diiodide as an initiator and tert-butyl peroxide as an oxidant, and takes cyclization reaction by mixing an alkynyl imine compound with a sulfonyl hydrazine compound to obtain the 3-sulfonyl quinoline compounds.
The structure of the 3-sulfonyl quinoline compound is shown as a formula I; the structure of the alkynyl imine compound is shown as a formula II: the structure of the sulfonyl hydrazide compound is shown as a formula III:
wherein:
R 1 one selected from hydrogen, p-chloro or p-methyl;
R 2 one selected from phenyl, thienyl or cyclopropyl;
R 3 one selected from phenyl, tert-butyl or hydrogen;
R 4 selected from one of phenyl or thienyl.
The preparation method comprises the following steps:
(1) At a certain temperature, adding an alkynyl imine compound, a sulfonyl hydrazine compound and an organic solvent into a test tube reactor, and then adding diiodide pentoxide and tert-butyl peroxide, stirring to promote the reaction;
(2) After the reaction was completed, the reaction was quenched with saturated aqueous ammonium chloride solution, the organic phase was separated, the aqueous phase was extracted three times with diethyl ether, the organic phases were combined, dried over anhydrous sodium sulfate, desolventized, and purified with petroleum ether: eluting with ethyl acetate=3:1, and performing column chromatography to obtain white solid, namely the target product.
The organic solvent is one of tetrahydrofuran, acetonitrile or 1, 2-dichloroethane. The organic solvent is a solvent having a good solubility for the reaction substrate.
The alkynyl imine compound: sulfonyl hydrazide compound: diiodo pentoxide: the molar ratio of the tert-butyl peroxy alcohol is 1:1.2-1.5:1:2.5-3.0. The raw materials are saved, and the reaction is ensured to be completely carried out.
The reaction temperature is 60-80 ℃ and the reaction time is 8-12 hours. The reaction time is too long to increase the reaction cost, and on the contrary, the completion of the reaction is difficult to ensure. In the actual reaction process, the real-time monitoring of whether the reaction is complete or not can be performed by thin layer chromatography.
In the preparation method, the required raw materials are all existing compounds, and can be prepared by adopting commercial products or the existing method. For example, the alkynyl imine can be prepared by the existing method, namely, the chloro imine and the terminal alkyne are coupled under the action of cuprous iodide and alkali, which are all the prior art; the sulfonyl hydrazides, diiodium pentoxide and tert-butyl peroxy alcohol are commercially available.
The reaction mechanism of the preparation reaction is shown in figure 1:
firstly, diiodide is a free radical initiator, the positive pentavalent iodine in diiodide has strong oxidizing property, and simultaneously, under the action of diiodide, sulfonyl hydrazine releases a molecule of nitrogen to generate sulfonyl free radicals in one step due to the existence of peroxy-tert-butyl alcohol, and diiodide is reduced into iodine simple substance;
then, the sulfonyl radical attacks the alkyne bond of the alkynyl imine compound and carries out cyclization reaction to obtain a cyclic intermediate; after the intermediate passes through a single electron transfer process, under the condition of water participation, the 3-sulfonyl quinoline compound is finally obtained.
The preparation method specifically comprises the following steps:
a25 mL test tube reactor was taken and added with 0.5mmol of alkynyl imine, 0.6mmol of sulfonyl hydrazide and 5mL of acetonitrile. To the reaction system, 0.5mmol of diiodo pentoxide and 2.5mmol of t-butyl peroxide were added at 70℃and stirred for 8 hours. The progress of the reaction was checked by TLC (petroleum ether: ethyl acetate=3:1). After completion of the reaction, the reaction was quenched with 20mL of saturated aqueous ammonium chloride, the organic phase was separated, the aqueous phase was extracted three times with diethyl ether (50 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, desolventized, and petroleum ether was used: eluting with ethyl acetate=3:1, and performing column chromatography to obtain white solid, namely the target product. The reaction process is shown in the following formula:
example 2:
a25 mL test tube reactor was taken and added with 0.5mmol of alkynyl imine, 0.6mmol of sulfonyl hydrazide and 5mL of acetonitrile. To the reaction system, 0.5mmol of diiodo pentoxide and 2.5mmol of t-butyl peroxide were added at 70℃and stirred for 8 hours. The progress of the reaction was checked by TLC (petroleum ether: ethyl acetate=3:1). After completion of the reaction, the reaction was quenched with 20mL of saturated aqueous ammonium chloride, the organic phase was separated, the aqueous phase was extracted three times with diethyl ether (50 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, desolventized, and petroleum ether was used: eluting with ethyl acetate=3:1, and performing column chromatography to obtain a white solid, namely the 3-sulfonyl quinoline compound, wherein the yield is as follows: 74, the structural formula is as follows:
nuclear magnetic resonance of% 1 HNMR and 13 c NMR) detection data were:
1 H NMR(500MHz,CDCl 3 )δ8.19(d,J＝8.0Hz,1H),8.05–7.94(m,5H),7.76–7.71(m,3H),7.59–7.55(m,2H),7.54–7.49(m,3H),7.48–7.46(m,1H),7.45–7.41(m,2H),7.37–7.34(m,2H)；
13 C NMR(126MHz,CDCl 3 )δ159.0,149.8,146.4,141.8,140.9,138.1,133.7,129.8,129.6,129.5,129.4,129.3,128.7,128.6,128.5,128.3,128.0,127.9,127.4,126.4,118.6。
example 3:
a25 mL test tube reactor was taken and added with 0.5mmol of alkynyl imine, 0.6mmol of sulfonyl hydrazide and 5mL of acetonitrile. To the reaction system, 0.5mmol of diiodo pentoxide and 2.5mmol of t-butyl peroxide were added at 70℃and stirred for 8 hours. The progress of the reaction was checked by TLC (petroleum ether: ethyl acetate=3:1). After completion of the reaction, the reaction was quenched with 20mL of saturated aqueous ammonium chloride, the organic phase was separated, the aqueous phase was extracted three times with diethyl ether (50 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, desolventized, and petroleum ether was used: eluting with ethyl acetate=3:1, and performing column chromatography to obtain a white solid, namely the 3-sulfonyl quinoline compound, wherein the yield is as follows: 71, the structural formula is as follows:
nuclear magnetic resonance of% 1 HNMR and 13 c NMR) detection data were:
1 H NMR(500MHz,CDCl 3 )δ8.09(d,J＝9.0Hz,1H),7.95–7.84(m,5H),7.76–7.69(m,2H),7.61–7.52(m,4H),7.52–7.46(m,3H),7.37–7.32(m,2H),7.15(s,1H)；
13 C NMR(126MHz,CDCl 3 )δ157.9,149.1,144.9,141.8,140.9,138.3,137.5,133.7,132.2,129.8,129.5,129.3,129.2,128.6,128.5,128.4,128.2,128.0,127.9,125.1,118.6。
example 4:
a25 mL test tube reactor was taken and added with 0.5mmol of alkynyl imine, 0.6mmol of sulfonyl hydrazide and 5mL of acetonitrile. To the reaction system, 0.5mmol of diiodo pentoxide and 2.5mmol of t-butyl peroxide were added at 70℃and stirred for 8 hours. The progress of the reaction was checked by TLC (petroleum ether: ethyl acetate=3:1). After completion of the reaction, the reaction was quenched with 20mL of saturated aqueous ammonium chloride, the organic phase was separated, the aqueous phase was extracted three times with diethyl ether (50 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, desolventized, and petroleum ether was used: eluting with ethyl acetate=3:1, and performing column chromatography to obtain a white solid, namely the 3-sulfonyl quinoline compound, wherein the yield is as follows: 78, the structural formula is as follows:
nuclear magnetic resonance of% 1 HNMR and 13 c NMR) detection data were:
1 H NMR(500MHz,CDCl 3 )δ8.06(d,J＝9.0Hz,1H),7.88–7.76(m,5H),7.64(d,J＝7.0Hz,2H),7.59–7.52(m,4H),7.50–7.43(m,3H),7.28(d,J＝7.0Hz,2H),7.14(s,1H),2.40(s,3H)；
13 C NMR(126MHz,CDCl 3 )δ161.0,154.0,145.5,143.8,142.4,141.8,137.4,133.7,132.4,129.6,129.4,129.2,129.1,128.7,128.5,128.4,128.2,128.0,127.4,125.6,21.8。
example 5:
a25 mL test tube reactor was taken and added with 0.5mmol of alkynyl imine, 0.6mmol of sulfonyl hydrazide and 5mL of acetonitrile. To the reaction system, 0.5mmol of diiodo pentoxide and 2.5mmol of t-butyl peroxide were added at 70℃and stirred for 8 hours. The progress of the reaction was checked by TLC (petroleum ether: ethyl acetate=3:1). After completion of the reaction, the reaction was quenched with 20mL of saturated aqueous ammonium chloride, the organic phase was separated, the aqueous phase was extracted three times with diethyl ether (50 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, desolventized, and petroleum ether was used: eluting with ethyl acetate=3:1, and performing column chromatography to obtain a white solid, namely the 3-sulfonyl quinoline compound, wherein the yield is as follows: 85, the structural formula is as follows:
nuclear magnetic resonance of% 1 HNMR and 13 c NMR) detection data were:
1 H NMR(500MHz,CDCl 3 )δ8.16(d,J＝8.0Hz,1H),8.05–7.94(m,5H),7.89(d,J＝3.0Hz,1H),7.71(dd,J＝11.0,4.0Hz,1H),7.59–7.53(m,3H),7.51(d,J＝5.0Hz,1H),7.36(dd,J＝13.0,7.0Hz,2H),7.30–7.26(m,2H),7.15(dd,J＝5.0,4.0Hz,1H)；
13 C NMR(126MHz,CDCl 3 )δ155.5,154.5,146.8,145.2,142.5,141.8,133.7,130.3,130.1,129.6,129.2,129.1,128.7,128.5,128.3,128.1,127.4,127.3,126.9,126.8。
example 6:
a25 mL test tube reactor was taken and added with 0.5mmol of alkynyl imine, 0.6mmol of sulfonyl hydrazide and 5mL of acetonitrile. To the reaction system, 0.5mmol of diiodo pentoxide and 2.5mmol of t-butyl peroxide were added at 70℃and stirred for 8 hours. The progress of the reaction was checked by TLC (petroleum ether: ethyl acetate=3:1). After completion of the reaction, the reaction was quenched with 20mL of saturated aqueous ammonium chloride, the organic phase was separated, the aqueous phase was extracted three times with diethyl ether (50 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, desolventized, and petroleum ether was used: eluting with ethyl acetate=3:1, and performing column chromatography to obtain a white solid, namely the 3-sulfonyl quinoline compound, wherein the yield is as follows: 76, the structural formula is as follows:
nuclear magnetic resonance of% 1 H NMR 13 C NMR) detection data were:
1 H NMR(500MHz,CDCl 3 )δ8.53(d,J＝9.0Hz,1H),8.12(d,J＝8.0Hz,1H),7.95–7.84(m,5H),7.74–7.68(m,1H),7.65(dd,J＝8.0,1.0Hz,2H),7.61–7.55(m,1H),7.47(m,3H),2.13(m,1H),1.45–1.39(m,2H),0.92(m,2H)；
13 C NMR(126MHz,CDCl 3 )δ159.2,148.1,146.4,141.7,141.2,133.8,130.1,129.6,129.4,129.3,129.1,128.5,128.3,128.0,126.7,124.6,122.2,15.0,10.1。
example 7:
a25 mL test tube reactor was taken and added with 0.5mmol of alkynyl imine, 0.6mmol of sulfonyl hydrazide and 5mL of acetonitrile. To the reaction system, 0.5mmol of diiodo pentoxide and 2.5mmol of t-butyl peroxide were added at 70℃and stirred for 8 hours. The progress of the reaction was checked by TLC (petroleum ether: ethyl acetate=3:1). After completion of the reaction, the reaction was quenched with 20mL of saturated aqueous ammonium chloride, the organic phase was separated, the aqueous phase was extracted three times with diethyl ether (50 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, desolventized, and petroleum ether was used: eluting with ethyl acetate=3:1, and performing column chromatography to obtain a white solid, namely the 3-sulfonyl quinoline compound, wherein the yield is as follows: 63, the structural formula is as follows:
nuclear magnetic resonance of% 1 HNMR and 13 c NMR) detection data were:
1 H NMR(500MHz,CDCl 3 )δ8.42(d,J＝9.0Hz,1H),8.13–8.04(m,5H),7.99(d,J＝8.0Hz,1H),7.78–7.69(m,3H),7.63(t,J＝8.0Hz,1H),7.50(d,J＝7.0Hz,2H),7.47(t,J＝8.0Hz,1H),1.72(s,9H)；
13 C NMR(126MHz,CDCl 3 )δ165.2,152.7,145.5,141.8,133.7,131.2,129.7,129.5,129.3,128.9,128.7,128.1,127.9,127.6,125.8,124.1,41.3,30.1。
example 8:
a25 mL test tube reactor was taken and added with 0.5mmol of alkynyl imine, 0.6mmol of sulfonyl hydrazide and 5mL of acetonitrile. To the reaction system, 0.5mmol of diiodo pentoxide and 2.5mmol of t-butyl peroxide were added at 70℃and stirred for 8 hours. The progress of the reaction was checked by TLC (petroleum ether: ethyl acetate=3:1). After completion of the reaction, the reaction was quenched with 20mL of saturated aqueous ammonium chloride, the organic phase was separated, the aqueous phase was extracted three times with diethyl ether (50 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, desolventized, and petroleum ether was used: eluting with ethyl acetate=3:1, and performing column chromatography to obtain a white solid, namely the 3-sulfonyl quinoline compound, wherein the yield is as follows: 79, its structural formula is as follows:
nuclear magnetic resonance of% 1 H NMR 13 C NMR) detection data were:
1 H NMR(500MHz,CDCl 3 )δ8.87(s,1H),8.18(d,J＝8.0Hz,1H),7.75(dd,J＝11.0,4.0Hz,2H),7.66–7.61(m,2H),7.55(m,3H),7.49–7.42(m,4H),7.35(d,J＝7.0Hz,2H)；
13 C NMR(126MHz,CDCl 3 )δ157.4,150.0,146.3,142.5,137.9,134.0,130.1,129.7,129.5,129.3,129.2,128.9,128.6,128.1,127.8,127.7,126.5。
example 9:
a25 mL test tube reactor was taken and added with 0.5mmol of alkynyl imine, 0.6mmol of sulfonyl hydrazide and 5mL of acetonitrile. To the reaction system, 0.5mmol of diiodo pentoxide and 2.5mmol of t-butyl peroxide were added at 70℃and stirred for 8 hours. The progress of the reaction was checked by TLC (petroleum ether: ethyl acetate=3:1). After completion of the reaction, the reaction was quenched with 20mL of saturated aqueous ammonium chloride, the organic phase was separated, the aqueous phase was extracted three times with diethyl ether (50 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, desolventized, and petroleum ether was used: eluting with ethyl acetate=3:1, and performing column chromatography to obtain a white solid, namely the 3-sulfonyl quinoline compound, wherein the yield is as follows: 82, the structural formula is as follows:
nuclear magnetic resonance of% 1 H NMR 13 C NMR) detection data were:
1 H NMR(500MHz,CDCl 3 )δ8.12(d,J＝8.0Hz,1H),8.03–7.91(m,5H),7.87(d,J＝3.0Hz,1H),7.66(dd,J＝11.0,4.0Hz,1H),7.57–7.52(m,3H),7.47(d,J＝5.0Hz,2H),7.30–7.26(m,4H)；
13 C NMR(126MHz,CDCl 3 )δ154.3,153.1,145.7,144.1,141.4,140.7,132.6,131.3,130.8,129.6,129.0,128.9,127.8,127.4,127.2,127.0,126.6,126.3,125.1,121.7。
the above embodiments are only for illustrating the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the content of the present invention and implement the same, and are not intended to limit the scope of the present invention. All equivalent changes or modifications made in accordance with the essence of the present invention are intended to be included within the scope of the present invention.
Claims (7)
1. A preparation method of a 3-sulfonyl quinoline compound is characterized by comprising the following steps: taking diiodide as an initiator and tert-butyl peroxide as an oxidant, mixing an alkynyl imine compound with a sulfonyl hydrazine compound to perform cyclization reaction to obtain a 3-sulfonyl quinoline compound,
the structure of the 3-sulfonyl quinoline compound is shown as a formula I; the structure of the alkynyl imine compound is shown as a formula II: the structure of the sulfonyl hydrazide compound is shown as a formula III:
wherein:
said R is 1 One selected from hydrogen, p-chloro or p-methyl;
said R is 2 One selected from phenyl, thienyl or cyclopropyl;
said R is 3 One selected from phenyl, tert-butyl or hydrogen;
said R is 4 Selected from one of phenyl or thienyl.
2. The method for preparing 3-sulfonyl quinoline compound according to claim 1, wherein the method comprises the following steps:
(1) At a certain temperature, adding an alkynyl imine compound, a sulfonyl hydrazine compound and an organic solvent into a test tube reactor, and then adding diiodide pentoxide and tert-butyl peroxide, stirring to promote the reaction;
(2) After the reaction was completed, the reaction was quenched with saturated aqueous ammonium chloride solution, the organic phase was separated, the aqueous phase was extracted three times with diethyl ether, the organic phases were combined, dried over anhydrous sodium sulfate, desolventized, and purified with petroleum ether: eluting with ethyl acetate=3:1, and performing column chromatography to obtain white solid, namely the target product.
3. The method for preparing 3-sulfonyl quinoline compound according to claim 2, wherein the method comprises the following steps: the organic solvent is one of tetrahydrofuran, acetonitrile or 1, 2-dichloroethane.
4. The method for preparing 3-sulfonyl quinoline compound according to claim 2, wherein the method comprises the following steps: the alkynyl imine compound: sulfonyl hydrazide compound: diiodo pentoxide: the molar ratio of the tert-butyl peroxy alcohol is 1:1.2-1.5:1:2.5-3.0.
5. The method for preparing 3-sulfonyl quinoline compound according to claim 2, wherein the method comprises the following steps: the reaction temperature is 60-80 ℃ and the reaction time is 8-12 hours.
6. The preparation method of the 3-sulfonyl quinoline compound according to claim 2, wherein the preparation method specifically comprises the following steps:
taking a 25mL test tube reactor, adding 0.5mmol of alkynyl imine, 0.6mmol of sulfonyl hydrazine and 5mL of acetonitrile, adding 0.5mmol of diiodine pentoxide and 2.5mmol of tert-butyl peroxide into the reaction system, and stirring for 8 hours; the progress of the reaction was checked by TLC for petroleum ether: ethyl acetate=3:1; after the reaction was completed, the reaction was quenched with 20mL of saturated aqueous ammonium chloride solution, the organic phase was separated, the aqueous phase was extracted three times with 50mL of diethyl ether each time, the organic phases were combined, dried over anhydrous sodium sulfate, desolventized, and petroleum ether was used: eluting with ethyl acetate=3:1, and performing column chromatography to obtain white solid, namely the target product.
7. The method for producing 3-sulfonylquinoline compounds according to any one of claims 1 to 6, wherein the reaction mechanism of the production reaction is:
firstly, diiodide is a free radical initiator, the positive pentavalent iodine in diiodide has strong oxidizing property, and simultaneously, under the action of diiodide, sulfonyl hydrazine releases a molecule of nitrogen to generate sulfonyl free radicals in one step due to the existence of peroxy-tert-butyl alcohol, and diiodide is reduced into iodine simple substance;
then, the sulfonyl radical attacks the alkyne bond of the alkynyl imine compound and carries out cyclization reaction to obtain a cyclic intermediate; after the intermediate passes through a single electron transfer process, under the condition of water participation, the 3-sulfonyl quinoline compound is finally obtained.
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| Continuous Flow as Enabling Technology: Synthesis of Heteroaromatic Sulfinates as Bench Stable Cross-Coupling Partners;Fabio Lima等;《Organic Letters》;第22卷(第15期);第6082-6085页 * |
| I2O5 promoted iodosulfenylation of indoles under metal-free conditions;Wangyang Wang等;《Tetrahedron Letters》;第60卷;第1891-1894页 * |
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