A methyl sulfide derivative, and a preparation method and application thereof

Abstract

The application discloses a methyl sulfonate derivative and a preparation method and application thereof. The preparation method comprises the following steps: (1) adding carboxylic acid, dimethyl sulfoxide (DMSO) and potassium fluoride (KF) into a pressure-resistant reaction bottle, and heating at 180 DEG C for 6 hours through an oil bath; (2) after the reaction is completed, the obtained substance is extracted with ethyl acetate for three times, the organic layer is washed with water for two times in sequence, the washed organic layer is dried with anhydrous sodium sulfate, filtration is conducted, and a filtrate is obtained; (3) the obtained filtrate is concentrated under reduced pressure, the concentrated residue is separated and purified by using a silica gel column chromatography, and the methyl sulfonate derivative is obtained. The preparation method directly uses KF to catalyze the reaction of carboxylic acid and DMSO, does not need to use complex substrates, noble metal catalysts and phosphorus ligands, and has the advantages of simple operation, greenness, low cost and high yield (up to 92%).

Description

Technical Field

[0001] This invention belongs to the field of compound synthesis technology, specifically relating to a methyl thioester derivative, its preparation method, and its application. Background Technology

[0002] Methylthioesters are widely found in pharmaceuticals and natural products and have attracted considerable attention due to their unique biological properties. Methylthioesters are typically synthesized via a multi-step process using methanethiol / sodium methylsulfate and acyl compounds. This method utilizes toxic, malodorous, and difficult-to-manage methanethiol / sodium methylsulfate, and is also environmentally unfriendly, severely limiting the industrial production of methylthioesters. In recent years, some new methods have been reported, such as:

[0003] (a) Preparation of methyl thioesters by palladium-catalyzed thiocarbonylation of aryl halides / aryl diazonium salts / amines with 4-methylthio-2-butanone and carbon monoxide (Chem. Sci., 2020, 11, 2187; J. Org. Chem., 2021, 86, 8797).

[0004] (b) Preparation of methyl thioesters by nickel and iridium-catalyzed radical thioesterification of carboxylic acids with dimethyl disulfide (Nat. Synth., 2023, 1).

[0005] However, these methods use toxic gases like carbon monoxide, precious metals like palladium or nickel and iridium, and require sulfur precursors such as 4-methylthio-2-butanone or dimethyl disulfide, as well as transition metal catalysts that are difficult to handle. Therefore, developing a green, simple, low-cost, and efficient method for preparing methyl thioesters is essential. Summary of the Invention

[0006] The purpose of this invention is to provide a novel method for preparing methyl thioester derivatives. This method directly uses KF catalysis to react carboxylic acids and DMSO, without the need for complex substrates, noble metal catalysts, and phosphorus ligands. It has the advantages of being simple to operate, green, low in cost, and high in yield (up to 92%).

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0008] The methyl thioester derivatives of this invention have the structure shown in the following general formula 1:

[0009]

[0010] Where R is phenyl, substituted phenyl, naphthyl, pyridyl, quinolinyl, substituted furanyl, or thiazolyl.

[0011] The methyl thioester derivatives of this invention, in their general structural formula, include, but are not limited to, the following structures:

[0012]

[0013] Wherein, 2a is phenyl, 2b-2m is substituted phenyl, and 2n-2r are naphthyl, pyridyl, quinolinyl, substituted furanyl, and thiazolyl, respectively.

[0014] The method for preparing the methyl thioester derivatives of the present invention includes the following steps:

[0015] (1) Add carboxylic acid, dimethyl sulfoxide (DMSO) and potassium fluoride (KF) to a pressure-resistant reaction flask, and heat in an oil bath at 170-190℃ for 5.5-6.5 h;

[0016] (2) After the reaction is complete, extract the substance obtained after the reaction with ethyl acetate 2 to 4 times. Wash the organic layer with water 1 to 3 times in sequence. Dry the washed organic layer with anhydrous sodium sulfate and filter to obtain the filtrate.

[0017] (3) The filtrate obtained by vacuum concentration is then purified by silica gel column chromatography to obtain methyl thioester derivatives.

[0018] Preferably, the preparation method of the methyl thioester derivatives of the present invention includes the following steps:

[0019] (1) Add carboxylic acid, dimethyl sulfoxide (DMSO) and potassium fluoride (KF) to a pressure-resistant reaction flask, and heat in an oil bath at 180°C for 6 hours;

[0020] (2) After the reaction is complete, the substance obtained after the reaction is extracted with ethyl acetate three times. The organic layer is washed with water twice in sequence. The washed organic layer is dried with anhydrous sodium sulfate and filtered to obtain the filtrate.

[0021] (3) The filtrate obtained by vacuum concentration is then purified by silica gel column chromatography to obtain methyl thioester derivatives.

[0022] The reduced pressure concentration is achieved by rotary evaporation.

[0023] The carboxylic acid described in this invention can be any of the aromatic carboxylic acids.

[0024] The ratio of carboxylic acid, dimethyl sulfoxide and potassium fluoride in this invention is: n(carboxylic acid):V(DMSO):n(KF)=0.3mmol:2mL:0.06mmol.

[0025] The oil described in this invention is dimethyl silicone oil.

[0026] The eluent for silica gel column chromatography described in this invention is petroleum ether / ethyl acetate, with a volume ratio of 10 to 30:1.

[0027] Preferably, the eluent for silica gel column chromatography of the present invention is petroleum ether / ethyl acetate, with a volume ratio of 15 to 25:1.

[0028] More preferably, the eluent for silica gel column chromatography of the present invention is petroleum ether / ethyl acetate, with a volume ratio of 20:1.

[0029] Beneficial effects:

[0030] 1. The method of this invention can directly use KF to catalyze the reaction of carboxylic acids and DMSO without the need for complex substrates, noble metal catalysts and phosphorus ligands. It has the advantages of simple operation, green operation, low cost and high yield (up to 92%), and provides a new method for the preparation of methyl thioester derivatives. Attached Figure Description

[0031] Figure 1 Compound 2a 1 H NMR spectrum

[0032] Figure 2 Compound 2a 13 C NMR spectrum

[0033] Figure 3 Compound 2b 1 H NMR spectrum

[0034] Figure 4 Compound 2b 13 C NMR spectrum

[0035] Figure 5 Compound 2c 1 H NMR spectrum

[0036] Figure 6 Compound 2c 13 C NMR spectrum

[0037] Figure 7 : Compound 2d 1 H NMR spectrum

[0038] Figure 8 : Compound 2d 13 C NMR spectrum

[0039] Figure 9 : compound 2e 1 H NMR spectrum

[0040] Figure 10 : compound 2e 13 C NMR spectrum

[0041] Figure 11 : compound 2f 1H NMR spectrum

[0042] Figure 12 : compound 2f 13 C NMR spectrum

[0043] Figure 13 2g of compound 1 H NMR spectrum

[0044] Figure 14 2g of compound 13 C NMR spectrum

[0045] Figure 15 : Compound 2h 1 H NMR spectrum

[0046] Figure 16 : Compound 2h 13 C NMR spectrum

[0047] Figure 17 Compound 2i 1 H NMR spectrum

[0048] Figure 18 Compound 2i 13 C NMR spectrum

[0049] Figure 19 : compound 2j 1 H NMR spectrum

[0050] Figure 20 : compound 2j 13 C NMR spectrum

[0051] Figure 21 : Compound 2k 1 H NMR spectrum

[0052] Figure 22 : Compound 2k 13 C NMR spectrum

[0053] Figure 23 Compound 2l 1 H NMR spectrum

[0054] Figure 24 Compound 2l 13 C NMR spectrum

[0055] Figure 25 Compound 2m 1 H NMR spectrum

[0056] Figure 26 Compound 2m 13 C NMR spectrum

[0057] Figure 27 : compound 2n 1 H NMR spectrum

[0058] Figure 28 : compound 2n 13 C NMR spectrum

[0059] Figure 29 : compound 2o 1 H NMR spectrum

[0060] Figure 30 : compound 2o 13 C NMR spectrum

[0061] Figure 31 : Compound 2p 1 H NMR spectrum

[0062] Figure 32 : Compound 2p 13 C NMR spectrum

[0063] Figure 33 : compound 2q 1 H NMR spectrum

[0064] Figure 34 : compound 2q 13 C NMR spectrum

[0065] Figure 35 : compound 2r 1 H NMR spectrum

[0066] Figure 36 : compound 2r 13 C NMR spectrum Detailed Implementation

[0067] The technical solution of the present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0068] Example 1: A method for preparing a methyl thioester derivative

[0069] 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF were added to a 5 mL pressure-resistant reaction flask, and the mixture was heated in an oil bath at 180 °C for 6 h. After the reaction, the mixture was extracted three times with 100 mL of ethyl acetate, and the organic layer was washed twice with tap water. The washed organic layer was then dried with anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (20:1) to obtain methyl thioester compound 2a with a yield of 87%.

[0070] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2a) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ8.00–7.99 (dd, J=8.4, 1.3Hz, 2H), 7.61–7.58 (t, J=7.4Hz, 1H), 7.49–7.47 (m, 2H), 2.51 (s, 3H). 13 C NMR (151MHz, CDCl3) δ192.51,137.08,133.28,128.62,127.14,11.73.

[0071] Example 2: A method for preparing a methyl thioester derivative

[0072] Add 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF to a 5 mL pressure-resistant reaction flask, and react in an oil bath at 180 °C for 6 h. After the reaction, extract twice with 100 mL of ethyl acetate, wash the organic layer once with tap water, dry the washed organic layer with anhydrous sodium sulfate, and filter. Concentrate the filtrate under reduced pressure, and then purify the residue by silica gel column chromatography (20:1) to obtain methyl thioester compound 2b; yield 80%.

[0073] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2b) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ7.61–7.59 (d, J=7.7Hz, 1H), 7.49–7.48 (dd, J=2.7, 1.6Hz, 2H), 7.39–7.35 (t,J=8.0Hz,2H),7.14–7.12(ddd,J=8.2,2.6,0.9Hz,3H),3.88–3.87(s,8H),2.49–2.49(s,7H). 13 C NMR (151MHz, CDCl3) δ192.41,159.75,138.41,129.63,119.75,119.67,111.44,55.48,11.82.

[0074] Example 3: A method for preparing a methyl thioester derivative

[0075] Add 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF to a 5 mL pressure-resistant reaction flask, and react in an oil bath at 180 °C for 6 h. After the reaction, extract twice with 100 mL of ethyl acetate, wash the organic layer twice with tap water, dry the washed organic layer with anhydrous sodium sulfate, and filter. Concentrate the filtrate under reduced pressure, and then purify the residue by silica gel column chromatography (30:1) to obtain methyl thioester compound 2c; yield 70%.

[0076] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2c) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ7.14–7.13 (d, J=2.3Hz, 2H), 6.68–6.67 (t, J=2.3Hz, 1H), 3.86 (s, 6H), 2.49 (s, 2H). 13 C NMR (151MHz, CDCl3) δ192.42,160.81,139.01,105.65,104.87,55.63,11.91.

[0077] Example 4: A method for preparing a methyl thioester derivative

[0078] Add 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF to a 5 mL pressure-resistant reaction flask, and react in an oil bath at 180 °C for 6 h. After the reaction, extract three times with 100 mL of ethyl acetate, wash the organic layer twice with tap water, dry the washed organic layer with anhydrous sodium sulfate, and filter. Concentrate the filtrate under reduced pressure, and then purify the residue by silica gel column chromatography (25:1) to obtain methyl thioester compound 2d; yield 46%.

[0079] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2d) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ7.64–7.62(dd,J=8.2,1.8Hz,1H),7.45–7.44(d,J=1.8Hz,1H),6.87–6.86(d,J=8.2Hz,1H),6.07(s,2H),2.47(s,3H). 13 C NMR (151MHz, CDCl3) δ190.77,151.93,148.04,131.64,123.18,108.04,107.18,101.94,11.82.

[0080] Example 5: A method for preparing a methyl thioester derivative

[0081] Add 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF to a 5 mL pressure-resistant reaction flask, and react in an oil bath at 180 °C for 6 h. After the reaction, extract three times with 100 mL of ethyl acetate, wash the organic layer twice with tap water, dry the washed organic layer with anhydrous sodium sulfate, and filter. Concentrate the filtrate under reduced pressure, and then purify the residue by silica gel column chromatography (25:1) to obtain methyl thioester compound 2e; yield 92%.

[0082] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2e) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ7.81–7.78(m,1H),7.41–7.39(d,J=7.6Hz,1H),7.37–7.33(t,J=7.8Hz,1H),2.49–2.49(s,3H),2.43–2.43(s,3H). 13 C NMR (151MHz, CDCl3) δ192.66,138.49,137.11,134.05,128.49,127.60,124.37,21.32,11.73.

[0083] Example 6: A method for preparing a methyl thioester derivative

[0084] Add 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF to a 5 mL pressure-resistant reaction flask, and react in an oil bath at 180 °C for 6 h. After the reaction, extract three times with 100 mL of ethyl acetate, wash the organic layer twice with tap water, dry the washed organic layer with anhydrous sodium sulfate, and filter. Concentrate the filtrate under reduced pressure, and then purify the residue by silica gel column chromatography (25:1) to obtain methyl thioester compound 2f; yield 88%.

[0085] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2f) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ7.90–7.88(d,J=8.3Hz,2H),7.27–7.26(d,J=8.0Hz,2H),2.49(s,3H),2.43(s,3H). 13C NMR (151MHz, CDCl3) δ192.10,144.11,134.57,129.27,127.20,21.67,11.64.

[0086] Example 7: A method for preparing a methyl thioester derivative

[0087] Add 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF to a 5 mL pressure-resistant reaction flask, and heat in an oil bath at 180 °C for 6 h. After the reaction, extract three times with 100 mL of ethyl acetate, wash the organic layer twice with tap water, dry the washed organic layer with anhydrous sodium sulfate, and filter. Concentrate the filtrate under reduced pressure, and then purify the residue by silica gel column chromatography (25:1) to obtain 2 g of methyl thioester compounds; yield 79%.

[0088] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2g) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ7.92–7.91(d,J=8.3Hz,2H),7.30–7.28(d,J=8.7Hz,2H),2.74–2.71(q,J=7.6Hz,2H),2.49(s,3H),1.29–1.27(t,J=7.6Hz,3H). 13 C NMR (151MHz, CDCl3) δ192.13,150.29,134.78,128.10,127.31,28.97,15.19,11.65.

[0089] Example 8: A method for preparing a methyl thioester derivative

[0090] Add 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF to a 5 mL pressure-resistant reaction flask, and react in an oil bath at 180 °C for 6 h. After the reaction, extract three times with 100 mL of ethyl acetate, wash the organic layer twice with tap water, dry the washed organic layer with anhydrous sodium sulfate, and filter. Concentrate the filtrate under reduced pressure, and then purify the residue by silica gel column chromatography (10:1) to obtain methyl thioester compounds for 2 h; yield 72%.

[0091] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2h) 1 H NMR and 13 The C NMR detection data are as follows: 1H NMR(600MHz, CDCl3)δ8.08–8.06(d,J=8.4Hz,2H),7.70–7.69(d,J=8.5Hz,2H),7.65 –7.64(d,J=7.0Hz,2H),7.51–7.48(t,J=7.7Hz,2H),7.44–7.42(m,1H),2.53(s,3H). 13 C NMR (151MHz, CDCl3) δ192.01,146.05,139.84,135.79,128.98,128.27,127.70,127.27,11.76.

[0092] Example 9: A method for preparing a methyl thioester derivative

[0093] Add 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF to a 5 mL pressure-resistant reaction flask, and heat in an oil bath at 180 °C for 6 h. After the reaction, extract three times with 100 mL of ethyl acetate, wash the organic layer twice with tap water, dry the washed organic layer with anhydrous sodium sulfate, and filter. Concentrate the filtrate under reduced pressure, and then purify the residue by silica gel column chromatography (25:1) to obtain methyl thioester compound 2i; yield 66%.

[0094] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2i) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ7.85–7.83 (d, J=8.7Hz, 2H), 6.66–6.65 (d, J=8.7Hz, 2H), 2.45 (s, 3H). 13 C NMR (151MHz, CDCl3) δ190.56,151.29,129.49,127.44,113.77,11.45.

[0095] Example 10: A method for preparing a methyl thioester derivative

[0096] 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF were added to a 5 mL pressure-resistant reaction flask, and the mixture was heated in an oil bath at 180 °C for 6 h. After the reaction, the mixture was extracted three times with 100 mL of ethyl acetate, and the organic layer was washed twice with tap water. The washed organic layer was then dried with anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (25:1) to obtain methyl thioester compound 2j; yield 42%.

[0097] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2j) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ8.11(s,1H),7.92–7.91(d,J=7.8Hz,1H),7.72–7.71(d,J=7.9Hz,1H),7.37–7.34(t,J=7.9Hz,1H),2.51(s,4H). 13 C NMR (151MHz, CDCl3) δ191.17,138.74,136.11,130.19,130.09,125.72,122.86,11.87.

[0098] Example 11: A method for preparing a methyl thioester derivative

[0099] Add 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF to a 5 mL pressure-resistant reaction flask, and react in an oil bath at 180 °C for 6 h. After the reaction, extract three times with 100 mL of ethyl acetate, wash the organic layer twice with tap water, dry the washed organic layer with anhydrous sodium sulfate, and filter. Concentrate the filtrate under reduced pressure, and then purify the residue by silica gel column chromatography (25:1) to obtain methyl thioester compound 2K; yield 75%.

[0100] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2k) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ8.09–8.06 (d, J=8.5Hz, 1H), 7.80–7.77 (d, J=8.5Hz, 1H), 2.55–2.55 (s, 2H). 13 C NMR (151MHz, CDCl3) δ191.16,140.11,132.53,127.60,117.86,116.58,12.01.

[0101] Example 12: A method for preparing a methyl thioester derivative

[0102] Add 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF to a 5 mL pressure-resistant reaction flask, and react in an oil bath at 180 °C for 6 h. After the reaction, extract three times with 100 mL of ethyl acetate, wash the organic layer twice with tap water, dry the washed organic layer with anhydrous sodium sulfate, and filter. Concentrate the filtrate under reduced pressure, and then purify the residue by silica gel column chromatography (25:1) to obtain 2 l of methyl thioester compounds; yield 52%.

[0103] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2l) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ8.83–8.81(s,1H),8.47–8.43(m,2H),8.32–8.28(d,J=7.7Hz,1H),7.74–7.67(t,J=8.0Hz,2H),2.57–2.57(s,5H). 13 C NMR (151MHz, CDCl3) δ190.44,138.32,132.64,129.89,127.49,122.16,12.03.

[0104] Example 13: A method for preparing a methyl thioester derivative

[0105] Add 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF to a 5 mL pressure-resistant reaction flask, and react in an oil bath at 180 °C for 6 h. After the reaction, extract three times with 100 mL of ethyl acetate, wash the organic layer twice with tap water, dry the washed organic layer with anhydrous sodium sulfate, and filter. Concentrate the filtrate under reduced pressure, and then purify the residue by silica gel column chromatography (25:1) to obtain 2 m of methyl thioester compounds; yield 65%.

[0106] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2m) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ10.12(s,1H),8.14–8.13(d,J=8.3Hz,2H),8.00–7.99(d,J=8.4Hz,2H),2.55(s,3H). 13 C NMR (151MHz, CDCl3) δ191.82,191.46,141.35,139.26,129.85,127.72,12.00.

[0107] Example 14: A method for preparing a methyl thioester derivative

[0108] Add 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF to a 5 mL pressure-resistant reaction flask, and react in an oil bath at 180 °C for 6 h. After the reaction, extract three times with 100 mL of ethyl acetate, wash the organic layer twice with tap water, dry the washed organic layer with anhydrous sodium sulfate, and filter. Concentrate the filtrate under reduced pressure, and then purify the residue by silica gel column chromatography (25:1) to obtain methyl thioester compound 2n; yield 71%.

[0109] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2n) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ8.56 (s, 1H), 8.03–7.99 (m, 2H), 7.92–7.89 (t, J = 8.8Hz, 2H), 7. 64–7.61(dd,J=8.1,6.7Hz,1H),7.60–7.57(ddd,J=8.1,6.9,1.3Hz,1H),2.56(s,3H). 13 C NMR (151MHz, CDCl3) δ192.43,135.75,134.38,132.48,129.58,128.49,128.46,128.43,127.82,126.91,123.14,11.87.

[0110] Example 15: A method for preparing a methyl thioester derivative

[0111] Add 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF to a 5 mL pressure-resistant reaction flask, and react in an oil bath at 180 °C for 6 h. After the reaction, extract three times with 100 mL of ethyl acetate, wash the organic layer twice with tap water, dry the washed organic layer with anhydrous sodium sulfate, and filter. Concentrate the filtrate under reduced pressure, and then purify the residue by silica gel column chromatography (25:1) to obtain methyl thioester compound 20; yield 58%.

[0112] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2o) 1 H NMR and 13 The C NMR detection data are as follows: 1H NMR(600MHz, CDCl3)δ9.21–9.20(d,J=2.0Hz,1H),8.82–8.81(dd,J=4.8,1.7Hz,1H),8.25–8 .23(ddd,J=8.0,2.3,1.7Hz,1H),7.45–7.42(ddd,J=8.0,4.8,0.9Hz,1H),2.55–2.54(s,3H). 13 C NMR (151MHz, CDCl3) δ191.01,153.73,148.44,134.47,132.63,123.56,11.71.

[0113] Example 16: A method for preparing a methyl thioester derivative

[0114] Add 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF to a 5 mL pressure-resistant reaction flask, and heat in an oil bath at 180 °C for 6 h. After the reaction, extract three times with 100 mL of ethyl acetate, wash the organic layer twice with tap water, dry the washed organic layer with anhydrous sodium sulfate, and filter. Concentrate the filtrate under reduced pressure, and then purify the residue by silica gel column chromatography (25:1) to obtain methyl thioester compound 2p; yield 42%.

[0115] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2p) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ8.34–8.32(d,J=8.5Hz,1H),8.28–8.26(d,J=8.5Hz,1H),8.09–8.08(d,J=8. 4Hz,1H),7.92–7.90(d,J=8.2Hz,1H),7.84–7.81(m,1H),7.70–7.67(t,J=7.5Hz,1H),2.52(s,3H). 13 C NMR (151MHz, CDCl3) δ194.72,151.62,147.13,137.47,130.46,130.35,130.16,128.69,127.72,117.00,11.73.

[0116] Example 17: A method for preparing a methyl thioester derivative

[0117] 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF were added to a 5 mL pressure-resistant reaction flask, and the mixture was heated in an oil bath at 180 °C for 6 h. After the reaction, the mixture was extracted three times with 100 mL of ethyl acetate, and the organic layer was washed twice with tap water. The washed organic layer was then dried with anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (25:1) to obtain methyl thioester compound 2q; yield 49%.

[0118] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2q) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ7.14–7.11 (d, J=3.5Hz, 1H), 6.17–6.15 (dd, J=3.4, 1.0Hz, 1H), 2.45–2.45 (s, 3H), 2.41–2.40 (s, 1H). 13 C NMR (151MHz, CDCl3) δ180.42,157.30,149.64,117.02,108.87,14.04,10.71.

[0119] Example 18: A method for preparing a methyl thioester derivative

[0120] Add 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF to a 5 mL pressure-resistant reaction flask, and react in an oil bath at 180 °C for 6 h. After the reaction, extract three times with 100 mL of ethyl acetate, wash the organic layer twice with tap water, dry the washed organic layer with anhydrous sodium sulfate, and filter. Concentrate the filtrate under reduced pressure, and then purify the residue by silica gel column chromatography (25:1) to obtain methyl thioester compound 2r; yield 60%.

[0121] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2r) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ7.82–7.81(dd,J=3.8,1.1Hz,1H),7.64–7.63(dd,J=4.9,1.2Hz,1H),7.14–7.13(dd,J=4.9,3.8Hz,1H),2.51(s,3H). 13 C NMR (151MHz, CDCl3) δ184.49,142.08,132.45,130.89,127.89,11.77.

[0122] To further verify the feasibility and effectiveness of the present invention and to select the optimal solution, the inventors conducted a series of experiments, as follows:

[0123] 1. Main Instruments and Materials

[0124] INOVA 600MHz NMR spectrometer (TMS internal standard), Varian Technologies China Co., Ltd.;

[0125] DMSO, Bailingwei Reagent Co., Ltd.;

[0126] Carboxylic acids, Bailingwei Reagent Co., Ltd.;

[0127] Thin-layer chromatography silica gel plates, Qingdao Marine Chemical Plant.

[0128] 2. Experiment

[0129] We selected carboxylic acid (0.3 mmol) and DMSO (2 mL) as substrates, and reacted them in an oil bath at 180 °C for 6 h. We optimized the catalyst (0.06 mmol), and the results are shown in Table 1. Table 1 shows that the highest yield was achieved with KF catalyst.

[0130] Table 1 Optimization of Reaction Conditions

[0131]

[0132] 0.3 mmol of carboxylic acid, 2 mL of DMSO, and 0.06 mmol of KF were added to a 5 mL pressure-resistant reaction flask, and the mixture was heated in an oil bath at 180 °C for 6 h. After the reaction, the mixture was extracted three times with 100 mL of ethyl acetate, and the organic layer was washed twice with tap water. The washed organic layer was then dried with anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (20:1) to obtain methyl thioester compound 2a with a yield of 87%.

[0133] Nuclear magnetic resonance (NMR) of the prepared methyl thioester derivative (2a) 1 H NMR and 13 The C NMR detection data are as follows: 1 H NMR (600MHz, CDCl3) δ8.00–7.99 (dd, J=8.4, 1.3Hz, 2H), 7.61–7.58 (t, J=7.4Hz, 1H), 7.49–7.47 (m, 2H), 2.51 (s, 3H). 13 C NMR (151MHz, CDCl3) δ192.51,137.08,133.28,128.62,127.14,11.73.

[0134] Although the present invention has been described in detail above with general descriptions, specific embodiments, and experiments, modifications or improvements can be made to it, which will be obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.

Claims

1. A method for preparing a methyl thioester derivative, the structure of which is shown in general formula 1 below: ， Its features are, Includes the following steps: (1) Add carboxylic acid, dimethyl sulfoxide (DMSO) and potassium fluoride (KF) to a pressure-resistant reaction flask, and heat in an oil bath at 170-190℃ for 5.5-6.5 h; (2) After the reaction is complete, extract the substance obtained after the reaction with ethyl acetate 2 to 4 times. Wash the organic layer with water 1 to 3 times in sequence. Dry the washed organic layer with anhydrous sodium sulfate and filter to obtain the filtrate. (3) The filtrate obtained by vacuum concentration was then purified by silica gel column chromatography to obtain methyl thioester derivatives. The methyl thioester derivatives are selected from the following structures: 。 2. The preparation method according to claim 1, characterized in that, Includes the following steps: (1) Add carboxylic acid, dimethyl sulfoxide (DMSO) and potassium fluoride (KF) to a pressure-resistant reaction flask, and heat in an oil bath at 180°C for 6 hours; (2) After the reaction is complete, the substance obtained after the reaction is extracted with ethyl acetate three times. The organic layer is washed with water twice in sequence. The washed organic layer is dried with anhydrous sodium sulfate and filtered to obtain the filtrate. (3) The filtrate obtained by vacuum concentration is then purified by silica gel column chromatography to obtain methyl thioester derivatives.

3. The preparation method according to any one of claims 1 or 2, characterized in that, The ratio of the carboxylic acid, dimethyl sulfoxide, and potassium fluoride is: n(carboxylic acid):V(DMSO):n(KF) = 0.3mmol:2mL:0.06mmol.

4. The preparation method according to any one of claims 1 or 2, characterized in that, The oil is dimethyl silicone oil.

5. The preparation method according to any one of claims 1 or 2, characterized in that, The eluent for the silica gel column chromatography is petroleum ether / ethyl acetate, with a volume ratio of 10 to 30:

1.

6. The preparation method according to claim 5, characterized in that, The eluent for the silica gel column chromatography is petroleum ether / ethyl acetate, with a volume ratio of 15–25:

1.

7. The preparation method according to claim 6, characterized in that, The eluent for the silica gel column chromatography was petroleum ether / ethyl acetate, with a volume ratio of 20:1.

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