Process for the synthesis of quinoline-2-xanthate

Abstract

The application belongs to the field of organic synthesis, and particularly relates to a quinoline-2-xanthate synthesis method. A quinoline-2-xanthate is prepared by reacting a raw material of formula 1 and a raw material of formula 2 under the assistance of a sulfonic anhydride of formula 3. R8 is a phenyl group, a substituted phenyl group or an electron-withdrawing group substituted alkyl group. The solvent of the reaction stage is at least one of a halogenated alkane, THF, water, acetone and ethyl acetate. The application can realize the mild and efficient conversion of the quinoline-2-xanthate based on a brand-new principle based on the combination of the formula 3 and the solvent.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis and relates to a method for synthesizing quinoline-2-xanthate. Background Technology

[0002] Xanthate esters are widely used in pharmaceutical chemistry, agriculture, polymer chemistry, and environmental chemistry. Among them, aryl xanthate esters are important organic synthesis intermediates, capable of being efficiently converted into aryl thiols, thioethers, and sulfur-containing heterocyclic compounds. Traditional methods for synthesizing aryl xanthate esters mainly involve the reaction of aryl diazonium salts with potassium ethyl xanthate; however, aryl diazonium salts are unstable and potentially explosive, limiting the industrial application of this type of reaction. In recent years, transition metal-catalyzed carbon-halogen cross-coupling reactions of aryl halides with potassium ethyl xanthate have also been reported. However, most aryl xanthate esters exhibit extremely low stability at high temperatures and in the presence of alkali, readily converting further into the corresponding aryl thioether compounds. In 2022, Professor Wang Qingmin's research group at Nankai University developed a photocatalyst-free visible light-induced method for synthesizing aryl xanthate esters from dibenzothiophene onium salts with potassium ethyl xanthate (Org. Lett., 2022, 24, 8895-8900). Recently, Dmitry I. Bugaenko and colleagues reported a novel method for preparing various aryl xanthate esters by reacting potassium xanthate with diaryl thioonium salts under transition metal-free conditions (Org. Lett., 2023, 25, 272-276). Despite these promising achievements, both dibenzothioonium salts and diaryl thioonium salts are difficult to obtain, requiring complex multi-step synthetic processes. Most importantly, all reported aryl xanthate esters are primarily limited to functionalized phenyl xanthate esters, with few reports on the synthesis of heterocyclic-substituted xanthate esters.

[0003] Quinolines are an important class of nitrogen-containing heterocyclic compounds with excellent biological activities, including antitumor, antibacterial, antituberculosis, antimalarial, antioxidant, and anti-HIV effects. If active xanthate fragments can be introduced into the quinoline skeleton to prepare a series of quinoline derivatives, it is highly likely that some novel, highly active drug molecules can be obtained. Therefore, developing techniques for introducing xanthate fragments into quinoline heterocycles and preparing diverse xanthate compounds containing quinoline heterocycles meets the needs of new drug discovery. This is not only one of the current research hotspots and focuses in this field, but also the driving force behind the completion of this invention. Summary of the Invention

[0004] To address the lack of existing methods for synthesizing quinoline-2-xanthate, the present invention aims to provide a mild and high-conversion method for synthesizing quinoline-2-xanthate.

[0005] Quinoline-C2-H has low activity, making direct nucleophilic coupling with xanthate esters difficult, especially under mild conditions. To address this problem, the present invention provides the following solution:

[0006] A method for synthesizing quinoline-2-xanthate involves reacting the raw materials of formula 1 and formula 2 with the assistance of sulfonic anhydride of formula 3 to obtain the product of formula 4.

[0007]

[0008] R1 to R6 are individually H, halogens, C1 to C 10 Alkyl groups, C1-C 10 alkoxy, phenyl, cyano, and C1-C substituents 10 Alkyl groups; or adjacent groups therein cyclize to form a ring structure;

[0009] The R7 mentioned above is C1 to C1. 10 Alkyl, phenyl, C1-C with substituents 10 Alkyl or substituted formyl groups;

[0010] The M is H, Na, K or NH4;

[0011] R8 is a phenyl group, a phenyl group with a substituent, or an alkyl group substituted with an electron-withdrawing group;

[0012] The substituent is at least one selected from alkyl, alkoxy, phenyl, cycloyl, trifluoromethyl, nitro, ester, amide, and aminoacyl groups;

[0013] The solvent used in the reaction stage is at least one of the following: haloalkanes, THF, water, acetone, and ethyl acetate.

[0014] This invention innovatively provides a synthetic approach for quinoline-2-xanthate via electrophilic activation-nucleophilic addition-elimination. It innovatively utilizes a compound of formula 3 as a catalytic activator to pre-catalyze an electrophilic reaction of NO on the quinoline ring of formula 1, thereby improving the activity of C2-H. This facilitates the selective nucleophilic attack of C2-H by formula 2, while simultaneously achieving the elimination by formula 3. The method described in this invention does not require special metal coordinating raw materials, and features mild reaction conditions, high selectivity, and high conversion rate.

[0015] In this invention, Formula 1 can be any quinoline N oxide with H at the 2-position. Considering cost and availability, for example, in Formula 1, R1 to R6 can be individually H, a halogen, a C1-C6 alkyl group, or a C1-C6 alkoxy group.

[0016] In this invention, Formula 2 can be any desired xanthic acid and its salt. For example, in Formula 2, R7 is either a C1-C6 alkyl group or a C1-C6 alkyl group with a substituent. The substituent can be at least one of C1-C6 alkoxy groups, trifluoromethyl groups, halogens, three- to six-membered cycloalkyl groups, three- to six-membered heterocyclic cycloalkyl groups, five-membered heterocyclic aryl groups, phenyl groups, and six-membered heterocyclic aryl groups.

[0017] In this invention, the raw material of Formula 2 can be used in appropriate excess. For example, considering cost, the molar ratio of the raw material of Formula 1 to the raw material of Formula 2 is 1:1 to 2.5, preferably 1:1.1 to 1.8.

[0018] In this invention, the coordination of the activator of Formula 3 and the solvent in the reaction stage is key to achieving synergistic effects and improving the conversion of quinoline-2-xanthate. Studies have shown that, in Formula 3, the sulfonic anhydride constructed from aromatic or electron-withdrawing R8 structures unexpectedly exhibits superior activity compared to anhydrides and acyl chlorides of other structures, and can unexpectedly achieve highly efficient conversion of quinoline-2-xanthate.

[0019] Preferably, R8 is trifluoromethyl, phenyl, or a substituted phenyl group;

[0020] Preferably, the substituted phenyl group is a phenyl group having at least one substituent selected from C1-C6 alkyl, C1-C6 alkoxy, nitro, halogen, and trifluoromethyl.

[0021] In this invention, the molar ratio of the raw material of Formula 1 and the sulfonic anhydride of Formula 3 is 1:1 to 2.5, preferably 1:1.1 to 1.8.

[0022] In this invention, the combination of the solvent and Formula 3 can unexpectedly achieve synergy, which can unexpectedly improve the activity of C2-H, facilitate nucleophilic attack and dissociation of Formula 3, and thus unexpectedly improve the conversion rate of quinoline-2-xanthate.

[0023] The haloalkanes in the solvent are C1-C3 chloroalkanes with two or more chlorine substitutions;

[0024] Preferably, the solvent is at least one selected from dichloromethane, dichloroethane, and THF, and more preferably THF. In this invention, the use of THF as a solvent unexpectedly further synergizes with Formula 3, improving the reaction conversion rate.

[0025] In this invention, there are no special requirements for the temperature of the reaction stage. For example, the temperature of the reaction stage is above 10°C, and can be further 15 to 50°C. Considering the simplicity of the process, the temperature of the reaction stage can be directly room temperature.

[0026] In this invention, the reaction time can be determined using known central control detection methods, such as TLC or HPLC to monitor the conversion of reactants and products. Experiments have shown that the process described in this invention can generally complete the reaction within 60 minutes (e.g., 10–60 minutes).

[0027] In this invention, after the reaction is complete, the quinoline-2-xanthate can be obtained from the reaction system based on known principles and procedures. For example, after the reaction, extraction is performed using a non-water-soluble solvent, followed by concentration, to obtain crude quinoline-2-xanthate. The non-water-soluble solvent can be dichloromethane, dichloroethane, ethyl acetate, etc.

[0028] In this invention, a refined product can be obtained from a crude product using known methods. For example, crude quinoline-2-xanthate can be purified by chromatographic treatment to obtain a refined quinoline-2-xanthate product.

[0029] In this invention, as a typical example, the eluent in the chromatographic purification stage is a mixed solvent of petroleum ether / ethyl acetate with a volume ratio of 6 to 15:1.

[0030] In this invention, there are no special requirements for the reaction atmosphere; considering the simplicity of the process, an air atmosphere can be used.

[0031] Beneficial effects:

[0032] This invention innovatively provides a synthetic approach for quinoline-2-xanthate via electrophilic activation-nucleophilic addition-elimination. It innovatively utilizes a compound of formula 3 as a catalytic activator to pre-catalyze an electrophilic reaction of NO on the quinoline ring of formula 1, thereby improving the activity of C2-H. This facilitates the selective nucleophilic attack of C2-H by formula 2, while simultaneously achieving the elimination by formula 3. The method described in this invention does not require special metal coordinating raw materials, and features mild reaction conditions, high selectivity, and high conversion rate.

[0033] In this invention, using Ts2O as an activator and THF as a solvent unexpectedly exhibits a better synergistic effect, which can further improve the conversion effect of quinoline-2-xanthate under mild conditions. Attached Figure Description

[0034] Figure 1 The product prepared in Example 1 1 H-NMR spectrum;

[0035] Figure 2 The product prepared in Example 1 13 C-NMR spectrum; Detailed implementation method:

[0036] The method for synthesizing quinoline-2-xanthate according to the present invention involves dispersing quinoline N-oxide raw material of formula 1, xanthic acid and its salt raw material of formula 2, and sulfonic anhydride of formula 3 in a solvent and reacting them to obtain the product of formula 4.

[0037] In this invention, thanks to the combination of the activator of Formula 3 and the solvent, a mild conversion of quinoline-2-xanthate can be unexpectedly achieved based on a novel principle:

[0038] As a typical example, the reaction principle of the present invention is as follows:

[0039]

[0040] In the following cases, unless otherwise stated, the room temperature is 20–35°C.

[0041] Example 1:

[0042]

[0043] At room temperature, quinoline nitroxide compound (0.3 mmol), potassium ethyl xanthate (0.45 mmol), tetrahydrofuran (solvent, 3 mL), and p-toluenesulfonic anhydride (activator, Ts₂O, 0.45 mmol) were added sequentially to a 10 mL reaction tube equipped with a magnetic stirrer. The mixture was stirred at room temperature for about 30 min, and the reaction was monitored by TLC. After the reaction was completed, dichloromethane (10 mL) and deionized water (10 mL) were added to the reaction solution, mixed thoroughly, and the organic phase was extracted. The aqueous phase was extracted twice with dichloromethane (2 × 10 mL). The organic phases were combined, and the organic solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography with a silica gel size of 200-300 mesh and petroleum ether / ethyl acetate (10:1 v / v) as the eluent, yielding 62.0 mg of the target product, with a yield of 83%.

[0044] The NMR spectrum data of the obtained product are as follows:

[0045] 1 H NMR (400MHz, CDCl3) δ8.18(d,J=8.5Hz,1H),8.12(d,J=8.5Hz,1H),7.85(d,J=8.1Hz,1H),7.75(t,J=7 .6Hz,1H),7.69(d,J=8.5Hz,1H),7.61(t,J=7.5Hz,1H),4.63(q,J=7.1Hz,2H),1.32(t,J=7.1Hz,3H); 13C NMR (100MHz, CDCl3) δ210.5,153.0,148.3,137.0,130.2,129.5,127.8,127.6,127.3,127.2,70.3,13.5; HRMS (ESI): m / z[M+H] + calcdfor C 12 H 12 NOS2:250.0355; found:250.0358.

[0046] Based on Example 1, the following adjustments were made to Formula 3 and the solvent in the processing, with the following results:

[0047]

[0048]

[0049] a Conditions: 1a (0.1 mmol, 1 equiv.), 2a (0.15 mmol, 1.5 equiv.), surfactant (activator, 0.15 mmol, 1.5 equiv.), solvent (1 mL), rt, 0.5 h. b 3aa yield passed 1 Identified by ¹H NMR. PyBroP: Tripyrrylphosphonium hexafluorophosphate bromide.

[0050] As shown in the table above, the combination of Ts2O and THF can unexpectedly achieve a better synergistic effect, which helps to further improve the reaction conversion rate of quinoline-2-xanthate under mild conditions.

[0051] Example 2:

[0052]

[0053] At room temperature, 6-bromoquinoline nitroxide compound (0.3 mmol), potassium ethyl xanthate (0.45 mmol), tetrahydrofuran (solvent, 3 mL), and Ts₂O (activator, 0.45 mmol) were added sequentially to a 10 mL reaction tube equipped with a magnetic stirrer. The mixture was stirred at room temperature for about 30 min, and the reaction was monitored by TLC. After the reaction was completed, dichloromethane (10 mL) and deionized water (10 mL) were added to the reaction solution, mixed thoroughly, and the organic phase was extracted. The aqueous phase was extracted twice with dichloromethane (2 × 10 mL). The organic phases were combined, and the organic solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography with a silica gel size of 200-300 mesh and petroleum ether / ethyl acetate (10:1 v / v) as the eluent, yielding 72.6 mg of the target product, with a yield of 74%.

[0054] The NMR spectrum data of the obtained product are as follows:

[0055] 1 H NMR (400MHz, CDCl3) δ8.09(d,J=8.3Hz,1H),7.98(d,J=14.2Hz,2H),7.80(d,J= 8.8Hz,1H),7.71(d,J=8.3Hz,1H),4.63(q,J=6.4Hz,2H),1.33(t,J=6.6Hz,3H); 13 CNMR(100MHz, CDCl3)δ210.0,153.7,146.8,135.8,133.7,131.2,129.6,128.3,128.0,121.9,70.5,13.5; HRMS(ESI):m / z[M+H] + calcd for C 12 H 11 BrNOS2:327.9460; found:327.9461.

[0056] Example 3:

[0057]

[0058] At room temperature, 6-methoxyquinoline nitroxide compound (0.3 mmol), potassium ethyl xanthate (0.45 mmol), tetrahydrofuran (solvent, 3 mL), and Ts2O (activator, 0.45 mmol) were added sequentially to a 10 mL reaction tube equipped with a magnetic stirrer. The mixture was stirred at room temperature for about 30 min, and the reaction was monitored by TLC. After the reaction was completed, dichloromethane (10 mL) and deionized water (10 mL) were added to the reaction solution, mixed thoroughly, and the organic phase was extracted. The aqueous phase was extracted twice with dichloromethane (2 × 10 mL). The organic phases were combined, and the organic solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography with a silica gel size of 200-300 mesh and petroleum ether / ethyl acetate (4:1 v / v) as the eluent, yielding 61.1 mg of the target product, with a yield of 73%.

[0059] The NMR spectrum data of the obtained product are as follows:

[0060] 1H NMR (400MHz, CDCl3) δ8.06(d,J=8.5Hz,1H),8.00(d,J=9.2Hz,1H),7.61(d,J=8.5Hz,1H),7.38(dd, J=9.2,2.3Hz,1H),7.07(d,J=2.1Hz,1H),4.61(q,J=7.1Hz,2H),3.92(s,3H),1.30(t,J=7.1Hz,3H); 13 C NMR (100MHz, CDCl3) δ211.2,158.8,149.7,144.5,135.7,131.0,128.6,127.7,122.9,104.9,70.3,55.6,13.5; HRMS (ESI): m / z[M+H] + calcdfor C 13 H 14 NO22S2:280.0460; found:280.0463.

[0061] Example 4:

[0062]

[0063] At room temperature, 4-chloroquinoline nitroxide compound (0.3 mmol), potassium ethyl xanthate (0.45 mmol), tetrahydrofuran (solvent, 3 mL), and Ts₂O (activator, 0.45 mmol) were added sequentially to a 10 mL reaction tube equipped with a magnetic stirrer. The mixture was stirred at room temperature for about 30 min, and the reaction was monitored by TLC. After the reaction was completed, dichloromethane (10 mL) and deionized water (10 mL) were added to the reaction solution, mixed thoroughly, and the organic phase was extracted. The aqueous phase was extracted twice with dichloromethane (2 × 10 mL). The organic phases were combined, and the organic solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography with a silica gel size of 200-300 mesh and petroleum ether / ethyl acetate (4:1 v / v) as the eluent, yielding 57.7 mg of the target product, with a yield of 68%.

[0064] The NMR spectrum data of the obtained product are as follows:

[0065] 1 H NMR (400MHz, CDCl3) δ8.22(d,J=8.4Hz,1H),8.12(d,J=8.4Hz,1H),7.84–7.7 5(m,2H),7.69(t,J=7.6Hz,1H),4.64(q,J=7.1Hz,2H),1.35(t,J=7.1Hz,3H); 13C NMR (100MHz, CDCl3) δ209.3,152.8,148.7,142.9,131.0,129.8,128.7,126.7,125.5,124.0,70.5,13.5; HRMS (ESI): m / z[M+H] + calcd for C 12 H 11 ClNOS2:283.9965; found:283.9968.

[0066] Example 5:

[0067]

[0068] At room temperature, quinoline nitroxide compound (0.3 mmol), potassium butyl xanthate (0.45 mmol), tetrahydrofuran (solvent, 3 mL), and Ts₂O (activator, 0.45 mmol) were added sequentially to a 10 mL reaction tube equipped with a magnetic stirrer. The mixture was stirred at room temperature for about 30 min, and the reaction was monitored by TLC. After the reaction was completed, dichloromethane (10 mL) and deionized water (10 mL) were added to the reaction solution, mixed thoroughly, and the organic phase was extracted. The aqueous phase was extracted twice with dichloromethane (2 × 10 mL). The organic phases were combined, and the organic solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography with a silica gel size of 200-300 mesh and petroleum ether / ethyl acetate (10:1 v / v) as the eluent, yielding 60.7 mg of the target product, with a yield of 73%.

[0069] The NMR spectrum data of the obtained product are as follows:

[0070] 1 H NMR (400MHz, CDCl3) δ8.16(d,J=8.5Hz,1H),8.10(d,J=8.5Hz,1H),7.82(d,J=8.1Hz,1H),7.73(t,J=7.7Hz,1H),7.66(d, J=8.5Hz,1H),7.58(t,J=7.5Hz,1H),4.53(t,J=6.5Hz,2H),1.66–1.58(m,2H),1.29–1.18(m,2H),0.79(t,J=7.4Hz,3H); 13 C NMR (100MHz, CDCl3) δ210.3,152.8,148.2,136.9,130.1,129.4,127.7,127.5,127.2,127.0,74.1,29.8,18.8,13.4; HRMS (ESI): m / z[M+H] + calcd for C14 H 16 NOS2:278.0668; found:278.0671.

[0071] Example 6:

[0072]

[0073] At room temperature, quinoline nitroxide compound (0.3 mmol), potassium (2-ethoxy)-ethyl xanthate (0.45 mmol), tetrahydrofuran (solvent, 3 mL), and Ts2O (activator, 0.45 mmol) were added sequentially to a 10 mL reaction tube equipped with a magnetic stirrer. The mixture was stirred at room temperature for about 30 min, and the reaction was monitored by TLC. After the reaction was completed, dichloromethane (10 mL) and deionized water (10 mL) were added to the reaction solution, mixed thoroughly, and the organic phase was extracted. The aqueous phase was extracted twice with dichloromethane (2 × 10 mL). The organic phases were combined, and the organic solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography with a silica gel size of 200-300 mesh and petroleum ether / ethyl acetate (6:1 v / v) as the eluent. 58.9 mg of the target product was obtained, with a yield of 67%.

[0074] The NMR spectrum data of the obtained product are as follows:

[0075] 1 H NMR (400MHz, CDCl3) δ8.16(d,J=8.5Hz,1H),8.11(d,J=8.5Hz,1H),7.83(d,J=8.1Hz,1H),7.80–7.69(m,2H) ,7.60(t,J=7.5Hz,1H),4.77–4.61(m,2H),3.72–3.59(m,2H),3.36(q,J=7.0Hz,2H),1.08(t,J=7.0Hz,3H); 13 C NMR (100MHz, CDCl3) δ210.4,153.1,148.2,136.9,130.1,129.5,127.8,127.5,127.3,127.1,73.1,67.3,66.6,15.0; HRMS (ESI): m / z[M+H] + calcd for C 14 H 16 NO2S2:294.0617; found:294.0622.

[0076] Example 7:

[0077]

[0078] At room temperature, quinoline nitroxide compound (0.3 mmol), potassium (2-trifluoromethyl)-ethyl xanthate (0.45 mmol), tetrahydrofuran (solvent, 3 mL), and Ts2O (activator, 0.45 mmol) were added sequentially to a 10 mL reaction tube equipped with a magnetic stirrer. The mixture was stirred at room temperature for about 30 min, and the reaction was monitored by TLC. After the reaction was completed, dichloromethane (10 mL) and deionized water (10 mL) were added to the reaction solution, mixed thoroughly, and the organic phase was extracted. The aqueous phase was extracted twice with dichloromethane (2 × 10 mL). The organic phases were combined, and the organic solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography with a silica gel size of 200-300 mesh and petroleum ether / ethyl acetate (8:1 v / v) as the eluent, yielding 68.5 mg of the target product, with a yield of 72%.

[0079] The NMR spectrum data of the obtained product are as follows:

[0080] 1 H NMR (400MHz, CDCl3) δ8.20(d,J=8.5Hz,1H),8.13(d,J=8.5Hz,1H),7.86(d,J=8.1Hz,1H),7.77(t,J=7.7H z,1H),7.68(d,J=8.5Hz,1H),7.62(t,J=7.5Hz,1H),4.76(t,J=6.2Hz,2H),2.52(qt,J=10.7,6.3Hz,2H); 13 C NMR (100MHz, CDCl3) δ210.2,152.2,148.4,137.3,130.3,129.5,128.0,127.6,127.4,127.1,125.3(q,J C-F =275.2Hz), 65.9(q,J C-F =3.5Hz), 32.8(q,J C-F =29.6Hz); 19 FNMR(376MHz, CDCl3)δ-64.93; HRMS(ESI):m / z[M+H] + calcd for C 13 H 11 F3NOS2:318.0229; found:318.0236.

[0081] Example 8:

[0082]

[0083] At room temperature, quinoline nitroxide compound (0.3 mmol), potassium cyclobutyl xanthate (0.45 mmol), tetrahydrofuran (solvent, 3 mL), and Ts₂O (activator, 0.45 mmol) were added sequentially to a 10 mL reaction tube equipped with a magnetic stirrer. The mixture was stirred at room temperature for about 30 min, and the reaction was monitored by TLC. After the reaction was completed, dichloromethane (10 mL) and deionized water (10 mL) were added to the reaction solution, mixed thoroughly, and the organic phase was extracted. The aqueous phase was extracted twice with dichloromethane (2 × 10 mL). The organic phases were combined, and the organic solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography with a silica gel size of 200-300 mesh and petroleum ether / ethyl acetate (8:1 v / v) as the eluent, yielding 60.2 mg of the target product, with a yield of 73%.

[0084] The NMR spectrum data of the obtained product are as follows:

[0085] 1 H NMR (400MHz, CDCl3) δ8.18(d,J=8.5Hz,1H),8.12(d,J=8.5Hz,1H),7.84(d,J=8.1Hz,1H),7.77–7.66(m,2H),7.60 (t,J=7.5Hz,1H),5.55–5.46(m,1H),2.47–2.36(m,2H),5.55–5.46(m,2H),1.85–1.74(m,1H),1.66–1.55(m,1H); 13 C NMR (100MHz, CDCl3) δ208.8,153.2,148.2,136.9,130.1,129.5,127.8,127.5,127.2,127.1,77.8,29.9,13.5; HRMS (ESI): m / z[M+H] + calcd for C 14 H 14 NOS2:276.0511; found:276.0506.

[0086] Example 9:

[0087]

[0088] At room temperature, quinoline nitroxide compound (0.3 mmol), potassium (2-thienyl)-methylxanthate (0.45 mmol), tetrahydrofuran (solvent, 3 mL), and Ts2O (activator, 0.45 mmol) were added sequentially to a 10 mL reaction tube equipped with a magnetic stirrer. The mixture was stirred at room temperature for about 30 min, and the reaction was monitored by TLC. After the reaction was completed, dichloromethane (10 mL) and deionized water (10 mL) were added to the reaction solution, mixed thoroughly, and the organic phase was extracted. The aqueous phase was extracted twice with dichloromethane (2 × 10 mL). The organic phases were combined, and the organic solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography with a silica gel size of 200-300 mesh and petroleum ether / ethyl acetate (8:1 v / v) as the eluent, yielding 71.3 mg of the target product, with a yield of 75%.

[0089] The NMR spectrum data of the obtained product are as follows:

[0090] 1 H NMR (400MHz, CDCl3) δ8.19(d,J=8.5Hz,1H),8.10(d,J=8.5Hz,1H),7.85(d,J=8.1Hz,1H),7.75(t,J=8. 0Hz,2H),7.60(t,J=7.5Hz,1H),7.20(d,J=5.1Hz,1H),6.99(s,1H),6.91(t,J=4.1Hz,1H),4.47(s,2H); 13 C NMR (100MHz, CDCl3) δ186.9,151.3,148.5,138.6,137.2,130.3,129.4,127.8,127.6,127.5,127.3,127.0,126.4,125.7,29.7; HRMS (ESI): m / z[M+H] + calcd for C 15 H 12 NOS3:318.0076; found:318.0079.

Claims

1. A method for synthesizing quinoline-2-xanthate, characterized in that, The raw materials of Formula 1 and Formula 2 are reacted with the aid of sulfonic anhydride of Formula 3 to obtain the product of Formula 4. Formula 1 Formula 2 Formula 3 Formula 4 R1 to R6 are individually H, halogens, C1 to C6 alkyl groups, or C1 to C6 alkoxy groups; In Formula 2, R7 is a C1-C6 alkyl group or a C1-C6 alkyl group with a substituent; the substituent is at least one of C1-C6 alkoxy, trifluoromethyl, halogen, three- to six-membered cycloalkyl, three- to six-membered heterocyclic cycloalkyl, five-membered heterocyclic aryl, phenyl, and six-membered heterocyclic aryl. The M is H, Na, K or NH4; R8 is trifluoromethyl, phenyl, or substituted phenyl; the substituted phenyl is a phenyl with at least one substituent selected from C1-C6 alkyl, C1-C6 alkoxy, nitro, halogen, and trifluoromethyl. The solvent used in the reaction stage is at least one of the following: haloalkanes, THF, water, acetone, and ethyl acetate.

2. The method for synthesizing quinoline-2-xanthate as described in claim 1, characterized in that, The molar ratio of the raw materials in Formula 1 and Formula 2 is 1:1 to 2.

5.

3. The method for synthesizing quinoline-2-xanthate as described in claim 2, characterized in that, The molar ratio of the raw materials in Formula 1 and Formula 2 is 1:1.1~1.

8.

4. The method for synthesizing quinoline-2-xanthate as described in claim 1, characterized in that, The molar ratio of the raw material in Formula 1 and the sulfonic anhydride in Formula 3 is 1:1 to 2.

5.

5. The method for synthesizing quinoline-2-xanthate as described in claim 4, characterized in that, The molar ratio of the raw material in Formula 1 and the sulfonic anhydride in Formula 3 is 1:1.1~1.

8.

6. The method for synthesizing quinoline-2-xanthate as described in claim 1, characterized in that, The halogenated alkanes in the solvent are C1-C3 chloroalkanes with two or more chlorine substitutions.

7. The method for synthesizing quinoline-2-xanthate as described in claim 1, characterized in that, The solvent is at least one of dichloromethane, dichloroethane, and THF.

8. The method for synthesizing quinoline-2-xanthate as described in claim 1, characterized in that, The temperature during the reaction stage is 15~50℃.

9. The method for synthesizing quinoline-2-xanthate as described in claim 1, characterized in that, After the reaction was completed, the product was extracted with a non-water-soluble solvent and then concentrated to obtain crude quinoline-2-xanthate.

10. The method for synthesizing quinoline-2-xanthate as described in claim 9, characterized in that, The crude quinoline-2-xanthate was purified by chromatographic treatment to obtain the refined quinoline-2-xanthate. The eluent in the chromatographic purification stage is a mixture of petroleum ether and ethyl acetate with a volume ratio of 6 to 15:1.

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