Sulfur-containing polyethylene glycol derivatives, preparation methods thereof, and applications in selective oxidation of alcoholic hydroxyl groups

Abstract

The present invention discloses a class of sulfur-containing polyethylene glycol derivatives, a preparation method thereof, and an application thereof in the selective oxidation of alcoholic hydroxyl groups. The derivatives are bis-methylthio polyethylene glycol and bis-methylsulfinyl polyethylene glycol, which are polyethylene glycol-supported methylthio and methylsulfinyl groups. The bis-methylthio polyethylene glycol can replace dimethyl sulfide as an activator in the Corey-Kim oxidation, and an important intermediate compound 2'-benzyloxycarbonyl-4"-oxoazithromycin A for the synthesis of tulathromycin is obtained with a yield of 78.8%; and 2'-benzyloxycarbonyl-4"-oxoazithromycin A is obtained with a yield of 90.3%. 5-O-(tert-butyldiphenylsilyl)-23-oxonimoctine, an important intermediate compound in the synthesis of moxidectin, is prepared using bis(methylsulfinyl)polyethylene glycol (PEG) as an oxidant in the Swern oxidation, replacing dimethyl sulfoxide. The sulfur-containing PEG derivatives of the present invention are low-cost to prepare and can be used in Corey-Kim and Swern oxidations, avoiding the use or production of foul-smelling dimethyl sulfide and providing a green environment for these reactions.

Description

Technical Field

[0001] The invention belongs to the technical field of preparation of sulfur-containing polyethylene glycol derivatives and application thereof in the selective oxidation of alcohol hydroxyl groups, and particularly relates to the preparation of bismethylthio polyethylene glycol and bismethylsulfinyl polyethylene glycol, and application thereof in the selective oxidation of secondary alcohol hydroxyl groups to ketone carbonyl groups. Background Art

[0002] The selective oxidation of alcoholic hydroxyl groups to keto carbonyl groups is a common organic functional group transformation reaction with important applications in organic synthesis. This functional group transformation can be achieved via the Corey-Kim oxidation (Equation A) or the Swern oxidation (Equation B).

[0003]

[0004] In the Corey-Kim oxidation reaction, N-chlorosuccinimide is typically used as the oxidant, and dimethyl sulfide is used as the activator. The reaction is carried out at low temperatures, followed by hydrogen removal with triethylamine to produce a carbonyl compound. In the Swern oxidation reaction, dimethyl sulfoxide is used as the oxidant in the presence of oxalyl chloride at low temperatures. Dehydrogenation converts the alcoholic hydroxyl group to a ketone carbonyl group, while dimethyl sulfoxide is simultaneously reduced to dimethyl sulfide. Both the Corey-Kim and Swern oxidations involve the use or production of dimethyl sulfide, which has a significant negative impact on the reaction and production environment.

[0005] To avoid the use of dimethyl sulfide in Corey-Kim oxidation and the formation of dimethyl sulfide in Swern oxidation, previous researchers have conducted some research and achieved improved results. Hideo Togo et al. supported methylthio or methylsulfinyl groups on imidazolium-type ionic liquids. These functional ionic liquids replaced dimethyl sulfide or dimethyl sulfoxide, respectively, in the Corey-Kim oxidation or Swern oxidation of alcohols, avoiding the use of dimethyl sulfide or the formation of dimethyl sulfide, achieving good results [Efficient Swern oxidation and Corey-Kim oxidation with ion-supported methyl sulfoxides and methylsulfides. Tetrahedron 2012, 68, 6849-6855]. However, these ionic liquids have excellent water solubility, making it difficult to recover and reuse them after the reaction.

[0006] John C. Vederas et al. reported an odorless Swern oxidation method. This method first uses polyethylene glycol-2000 (PEG-2000) and 6-methylthiohexanoic acid (1) as raw materials. In the presence of condensing agents DCC and 4-dimethylaminopyridine (DMAP), a methylthio group is supported on the polyethylene glycol via an ester structural unit to obtain a methylthio polyethylene glycol derivative (2). The methylthio structural unit is then oxidized to a methylsulfinyl group using periodic acid as an oxidant to obtain a methylsulfinyl polyethylene glycol derivative (3). This derivative is used instead of dimethyl sulfoxide in the Swern oxidation, avoiding the production of dimethyl sulfide. After the Swern oxidation reaction, the methylthio polyethylene glycol derivative can be recovered by a simple method and oxidized to regenerate the methylsulfinyl polyethylene glycol derivative, thereby realizing the recycling and reuse of this polyethylene glycol derivative in the Swern oxidation reaction [Modification of the Swern oxidation: use of a soluble polymer-bound, recyclable and odorless sulfoxide. J. Org. Chem. 1998, 63, 2407-2409].

[0007]

[0008] Despite its many advantages, this method still suffers from two problems. First, the preparation of these sulfur-containing polyethylene glycol derivatives requires 6-methylthiohexanoic acid, which is expensive and difficult to purchase. Second, the methylthio and methylsulfinyl groups are linked to the polyethylene glycol via ester structural units, which are unstable and will hydrolyze under acidic or alkaline conditions. Summary of the Invention

[0009] In view of the shortcomings of using or producing malodorous dimethyl sulfide in the classic Corey-Kim oxidation and Swern oxidation reactions, and the problems existing in the preparation and use of reported sulfur-containing polyethylene glycol derivatives, the present invention provides a new class of sulfur-containing polyethylene glycol derivatives and a preparation method thereof, as well as their use in Corey-Kim oxidation and Swern oxidation reactions.

[0010] The sulfur-containing polyethylene glycol derivative provided by the present invention is bis(methylthio) polyethylene glycol or bis(methylsulfinyl) polyethylene glycol; wherein the structure of the bis(methylthio) polyethylene glycol is:

[0011]

[0012] The structure of the bis(methylsulfinyl)polyethylene glycol is:

[0013]

[0014] Wherein n is an integer from 40 to 100.

[0015] The synthetic route and specific preparation method of the sulfur-containing polyethylene glycol derivative of the present invention are as follows:

[0016]

[0017] Step 1: Dissolve polyethylene glycol, p-toluenesulfonyl chloride, and triethylamine in dichloromethane, and stir the mixture at room temperature for 4 to 12 hours; adjust the pH to 6 to 7 with hydrochloric acid, and separate the organic layer; dry the organic layer over anhydrous sodium sulfate, evaporate part of the dichloromethane, and add methyl tert-butyl ether to precipitate a solid; filter, and vacuum dry the filter cake to obtain bis-p-toluenesulfonyl polyethylene glycol.

[0018] Step 2: Dissolve bis-p-toluenesulfonyl polyethylene glycol in water, add a 20% sodium methyl mercaptan aqueous solution under stirring at room temperature, and react at room temperature for 24 to 48 hours; extract the reaction solution with dichloromethane, dry the organic phase with anhydrous sodium sulfate, evaporate part of the dichloromethane, add methyl tert-butyl ether to precipitate a solid; filter, and vacuum dry the filter cake to obtain bis-methylthio polyethylene glycol.

[0019] Step 3: dissolving bis(methylthio)polyethylene glycol in methanol or acetonitrile, adding a 30% mass concentration of hydrogen peroxide aqueous solution, reacting at 0-35° C. for 2-4 hours, adding a saturated sodium sulfite aqueous solution to quench the reaction, evaporating the methanol or acetonitrile, and extracting with dichloromethane; drying the dichloromethane phase over anhydrous sodium sulfate, evaporating a portion of the dichloromethane, adding methyl tert-butyl ether to precipitate a solid; and filtering, and vacuum drying the filter cake to obtain bis(methylsulfinyl)polyethylene glycol.

[0020] In the above step 1, the molar ratio of the polyethylene glycol, p-toluenesulfonyl chloride, and triethylamine is preferably 1:2-3:2-3.

[0021] In the above step 2, the molar ratio of the bis-p-toluenesulfonyl polyethylene glycol to sodium methyl mercaptan is preferably 1:2-4.

[0022] In the above step 3, the molar ratio of the bis(methylthio)polyethylene glycol to hydrogen peroxide is preferably 1:5-10.

[0023] The present invention also provides the use of the above-mentioned bis(methylthio)polyethylene glycol as an activator in the Corey-Kim oxidation reaction instead of dimethyl sulfide; the preparation of 2'-benzyloxycarbonyl-4"-oxoazithromycin A, an essential intermediate in the synthesis of tulathromycin, and the preparation of 5-O-(tert-butyldiphenylsilyl)-23-oxonimoctin, an essential intermediate in the synthesis of moxidectin, are used as examples to illustrate this use.

[0024]

[0025] The invention discloses an application of 2'-benzyloxycarbonyl-4"-oxoazithromycin A, an essential intermediate in the synthesis of tulathromycin, in Corey-Kim oxidation. The specific method comprises the following steps: dissolving N-chlorosuccinimide in dichloromethane and cooling the mixture to -30 to -60°C; adding bis(methylthio)polyethylene glycol; and stirring the mixture at the same temperature for 0.5 to 1.5 hours; then adding 2'-benzyloxycarbonylazithromycin A; and continuing the reaction at the same temperature for 1 to 5 hours; then adding 4-dimethylaminopyridine or triethylamine; and continuing the reaction at the same temperature. After reacting for 0.5 to 1 hour, the mixture is moved to room temperature and reacted for 0.5 to 2 hours; hydrochloric acid is added until the pH reaches 4 to 5, the layers are separated, and the pH value of the aqueous phase is adjusted to 8 to 9 with sodium hydroxide to precipitate a white solid; the solid is filtered out and separated and purified by silica gel column chromatography to obtain 2'-benzyloxycarbonyl-4"-oxoazithromycin A; the molar ratio of N-chlorosuccinimide, bismethylthiopolyethylene glycol, 2'-benzyloxycarbonylazithromycin A, and 4-dimethylaminopyridine or triethylamine used in the reaction is 2 to 5:2 to 5:1:2 to 5.

[0026] The invention discloses an application of 5-O-(tert-butyldiphenylsilyl)-23-oxonimoctine, an essential intermediate in the synthesis of moxidectin, in Corey-Kim oxidation. The specific method comprises the following steps: dissolving N-chlorosuccinimide in dichloromethane and cooling the mixture to -30 to -60°C; adding bis(methylthio)polyethylene glycol; and stirring the mixture at the same temperature for 0.5 to 1.5 hours; then adding 5-O-(tert-butyldiphenylsilyl)nimoctine; and continuing the reaction at the same temperature for 1 to 5 hours; then adding triethylamine; and continuing the reaction at the same temperature for 0.5 to 1 hour before transferring the mixture to room temperature for the reaction. The reaction mixture is stirred for 0.5 to 2 hours; the reaction solution is washed with hydrochloric acid, a saturated sodium chloride aqueous solution, and water, respectively, and the layers are separated. The organic phase is dried over anhydrous sodium sulfate, and a portion of dichloromethane is evaporated. Methyl tert-butyl ether is added to precipitate a solid, which is then filtered; the filtrate is evaporated to dryness, and the resulting residue is separated and purified by silica gel column chromatography to obtain 5-O-(tert-butyldiphenylsilyl)-23-oxonimoctin; the molar ratio of N-chlorosuccinimide, bismethylthiopolyethylene glycol, 5-O-(tert-butyldiphenylsilyl)nimoctin, and triethylamine used in the reaction is 2 to 5:2 to 5:1:2 to 6.

[0027] The present invention also provides the use of the above-mentioned bis(methylsulfinyl)polyethylene glycol as an oxidant in a Swern oxidation reaction instead of dimethyl sulfoxide, for example, in the synthesis of 2'-benzyloxycarbonyl-4"-oxoazithromycin A, an essential intermediate for the synthesis of tulathromycin, and 5-O-(tert-butyldiphenylsilyl)-23-oxonimoctin, an essential intermediate for the synthesis of moxidectin. This use is specifically illustrated using the preparation of 5-O-(tert-butyldiphenylsilyl)-23-oxonimoctin, an essential intermediate for the synthesis of moxidectin, as an example.

[0028]

[0029] The invention discloses an application of 5-O-(tert-butyldiphenylsilyl)-23-oxonimoctine, an essential intermediate in the synthesis of moxidectin, in a Swern oxidation process. The specific method comprises the following steps: dissolving bis(methylsulfinyl)polyethylene glycol in dichloromethane and cooling the mixture to -50 to -70°C; adding oxalyl chloride; and stirring the mixture at the same temperature for 0.5 to 1.5 hours; then adding 5-O-(tert-butyldiphenylsilyl)nimoctine; and continuing the reaction at the same temperature for 1 to 5 hours; then adding triethylamine; and continuing the reaction at the same temperature for 0.5 to 1 hour; and then transferring the mixture to room temperature for reaction. The reaction mixture is stirred for 0.5 to 2 hours; the reaction solution is washed with hydrochloric acid, a saturated sodium chloride aqueous solution, and water, respectively, and then dried over anhydrous sodium sulfate. A portion of the dichloromethane is evaporated, and methyl tert-butyl ether is added to precipitate a solid, which is then filtered; the filtrate is evaporated to dryness, and the resulting residue is separated and purified by silica gel column chromatography to obtain 5-O-(tert-butyldiphenylsilyl)-23-oxonimoctin; the molar ratio of bis(methylsulfinylpolyethylene glycol), oxalyl chloride, 5-O-(tert-butyldiphenylsilyl)nimoctin, and triethylamine used in the reaction is 3 to 6:3 to 6:1:4 to 10.

[0030] The beneficial effects of the present invention are as follows:

[0031] 1. Compared with the polyethylene glycol-supported thioether or supported methylsulfinyl group disclosed in the prior art, the bis(methylthio)polyethylene glycol and bis(methylsulfinyl)polyethylene glycol in the present invention do not have an ester structural unit that is prone to side reactions in the molecule, and are more stable during reaction and post-processing.

[0032] 2. Compared with the preparation process of sulfur-containing polyethylene glycol derivatives reported in the prior art, the preparation method of the sulfur-containing polyethylene glycol derivatives of the present invention is simpler, the required raw materials are easily purchased, and the cost is lower.

[0033] 3. The bis(methylthio)polyethylene glycol and bis(methylsulfinyl)polyethylene glycol of the present invention replace dimethyl sulfide in the classic Corey-Kim oxidation and dimethyl sulfoxide in the Swern oxidation reaction, respectively, thereby avoiding the use or production of dimethyl sulfide with a foul odor and making the reaction green and environmentally friendly. DETAILED DESCRIPTION

[0034] The present invention is further described in detail below with reference to the embodiments, but the protection scope of the present invention is not limited to these embodiments.

[0035] The 2'-benzyloxycarbonyl azithromycin A used in the examples was prepared according to the method disclosed in patent CN102295672A; the 5-O-(tert-butyldiphenylsilyl) nimoctin used in the examples was prepared according to the method disclosed in patent CN117924311A.

[0036] Example 1

[0037] Preparation of sulfur-containing polyethylene glycol derivatives

[0038]

[0039] Step 1: Place 32.75 g (16.37 mmol) of polyethylene glycol-2000, 8.74 g (45.84 mmol) of p-toluenesulfonyl chloride, 6.9 mL (49.11 mmol) of triethylamine, and 170 mL of dichloromethane in a flask and stir at room temperature for 12 hours. Add 20 mL of water and adjust the pH to 6-7 with 1 mol / L hydrochloric acid. Separate the layers, dry the organic layer over anhydrous sodium sulfate, partially remove the dichloromethane, and add methyl tert-butyl ether to precipitate a solid. Filter the mixture, and vacuum dry the filter cake to obtain 35.26 g of bis-p-toluenesulfonyl polyethylene glycol as a white solid, with a yield of 93.3%.

[0040] Step 2: 20.00 g (8.67 mmol) of bis-p-toluenesulfonyl polyethylene glycol, 12.19 g (34.68 mmol) of a 20% aqueous solution of sodium methyl mercaptan, and 15 mL of water were placed in a flask and stirred at room temperature for 48 h. The reaction solution was extracted with dichloromethane (25 mL × 2 times), the organic phase was dried over anhydrous sodium sulfate, and part of the dichloromethane was evaporated. Methyl tert-butyl ether was added to precipitate a solid. The filter cake was filtered and vacuum dried to obtain 16.22 g of a white solid bis(methylthio)polyethylene glycol A with a yield of 90.5%. The structural characterization data are as follows: 1 HNMR (600MHz, CDCl3) δ (ppm): 3.49-3.78 (m, 243H), 2.69 (t, J = 6.9Hz, 4H), 2.14 (s, 6H).

[0041] Step 3: 10.00 g (4.78 mmol) of bis(methylthio)polyethylene glycol A was placed in a flask, dissolved in 30 mL of methanol, cooled to 0°C, and 0.54 g (47.8 mmol) of a 30% aqueous hydrogen peroxide solution was added. The mixture was reacted at 0°C for 0.5 h, then transferred to room temperature and continued to react for 2.5 h. The reaction was quenched by adding a saturated aqueous sodium sulfite solution. The methanol was evaporated, and then extracted with dichloromethane. The dichloromethane phase was dried over anhydrous sodium sulfate, and part of the dichloromethane was evaporated. Methyl tert-butyl ether was added to precipitate a solid. The filter cake was filtered and vacuum dried to obtain 9.66 g of white bis(methylsulfinyl)polyethylene glycol A, with a yield of 95.2%. Its structural characterization data are as follows: 1 HNMR (600MHz, CDCl3) δ (ppm): 3.50-3.79 (m, 214H), 3.00-3.07 (m, 2H), 2.89-2.95 (m, 2H), 2.66 (s, 6H).

[0042] Example 2

[0043] Preparation of 2'-benzyloxycarbonyl-4"-oxoazithromycin A by Corey-Kim oxidation

[0044] Take 0.69g (5.18mmol) N-chlorosuccinimide and 35mL dichloromethane in a flask, stir and cool to -60℃, add 40mL dichloromethane solution containing 10.67g (5.18mmol) bis(methylthio)polyethylene glycol A, and react at -60℃ for 1h; then add 15mL dichloromethane solution containing 1.04g (1.15mmol) 2'-benzyloxycarbonylazithromycin A, and react at -60℃ for 2h; then add 10mL 0.70g (5.7 The reaction mixture was stirred for 24 hours at -60°C for 0.5 h, then at room temperature for 1.5 h. Hydrochloric acid was added to a pH of 4-5, the layers were separated, and the pH of the aqueous phase was adjusted to 8-9 with a 20% aqueous sodium hydroxide solution to precipitate a white solid. The solid was filtered and purified by silica gel column chromatography (using a mixture of methanol and dichloromethane in a volume ratio of 1:20 as the eluent) to obtain 0.79 g of 2'-benzyloxycarbonyl-4"-oxoazithromycin A as a white solid, in a yield of 78.8%.

[0045] The organic phase obtained by separation was washed with water and dried over anhydrous sodium sulfate. After part of the dichloromethane was evaporated, methyl tert-butyl ether was added to precipitate the solid, which was filtered to obtain 9.51 g of a white solid containing bis(methylthio)polyethylene glycol A for recycling.

[0046] Example 3

[0047] Preparation of 5-O-(tert-butyldiphenylsilyl)-23-oxonimoctin by Corey-Kim oxidation

[0048] 0.12 g (0.90 mmol) of N-chlorosuccinimide was placed in a flask, dissolved in 5 mL of dichloromethane, cooled to -50°C, and 7 mL of a dichloromethane solution containing 1.88 g (0.90 mmol) of bis(methylthiopolyethylene glycol) A was added, and the mixture was reacted at -50°C for 1.0 h. 3 mL of a dichloromethane solution containing 0.26 g (0.30 mmol) of 5-O-(tert-butyldiphenylsilyl) nimoctin was then added, and the reaction was continued at -50°C for 2.0 h. 3 mL of a dichloromethane solution containing 0.18 g (1.78 mmol) of triethylamine was then added, and the mixture was reacted at -50°C for 0.5 h, and then at room temperature for another 0.5 h. The reaction solution was washed sequentially with 15 mL of 1% hydrochloric acid, 15 mL of saturated sodium chloride solution, and 15 mL of water. The organic phase was dried over anhydrous sodium sulfate, and some dichloromethane was evaporated. Methyl tert-butyl ether was added to precipitate a solid. The mixture was filtered and the filtrate was evaporated to dryness to obtain a residue. The residue was purified by silica gel column chromatography (using dichloromethane as eluent) and then crystallized from acetonitrile to obtain 0.23 g of 5-O-(tert-butyldiphenylsilyl)-23-oxonimoctin, with a yield of 90.3%. The filter cake obtained by filtration was dried to obtain 1.63 g of a white solid containing bis(methylthiopolyethylene glycol A) for recycling.

[0049] Example 4

[0050] Preparation of 5-O-(tert-butyldiphenylsilyl)-23-oxonimoctin by Swern oxidation

[0051] 3.75 g (1.77 mmol) of bis(methylsulfinyl)polyethylene glycol A was dissolved in 10 mL of dichloromethane, cooled to -70°C, and 7 mL of a dichloromethane solution containing 0.22 g (1.73 mmol) of oxalyl chloride was added, and the mixture was reacted at -70°C for 1.0 h. 8 mL of a dichloromethane solution containing 0.26 g (0.30 mmol) of 5-O-(tert-butyldiphenylsilyl)nimoctin was then added, and the mixture was reacted at -70°C for 2.0 h. 5 mL of a dichloromethane solution containing 0.30 g (2.96 mmol) of triethylamine was then added, and the mixture was reacted at -70°C for 0.5 h, and then at room temperature for another 0.5 h. The reaction solution was washed sequentially with 15 mL of 1% hydrochloric acid, 15 mL of saturated sodium chloride solution, and 15 mL of water. The organic phase was dried over anhydrous sodium sulfate, and the dichloromethane was partially evaporated. Methyl tert-butyl ether was added to precipitate a solid. The mixture was filtered and the filtrate was evaporated to dryness. The resulting residue was purified by silica gel column chromatography (using dichloromethane as the eluent) to obtain 0.15 g of 5-O-(tert-butyldiphenylsilyl)-23-oxonimoctin, with a yield of 58.9%. The filter cake obtained by filtration was dried to obtain 3.54 g of a white solid containing bis(methylsulfinylpolyethylene glycol A) and bis(methylthiopolyethylene glycol A), which was recovered for reuse.

Claims

1. Use of bis(methylthio)polyethylene glycol as an activator in the Corey-Kim oxidation reaction, wherein the structure of the bis(methylthio)polyethylene glycol is: Wherein n is an integer from 40 to 100.

2. The use of bis(methylthio)polyethylene glycol according to claim 1 as an activator in a Corey-Kim oxidation reaction, characterized in that: The Corey-Kim oxidation reaction is to oxidize 2'-benzyloxycarbonyl azithromycin A to prepare 2'-benzyloxycarbonyl-4''-oxoazithromycin A or 5- O -(tert-butyldiphenylsilyl) nimoctin oxidation preparation 5- O -(tert-Butyldiphenylsilyl)-23-oxonimoctin.

3. The use of bis(methylthio)polyethylene glycol according to claim 1 as an activator in a Corey-Kim oxidation reaction, characterized in that: The preparation method of the bis(methylthio)polyethylene glycol comprises the following steps: Step 1: Dissolve polyethylene glycol, p-toluenesulfonyl chloride, and triethylamine in dichloromethane and react with stirring at room temperature for 4 to 12 hours; adjust the pH to 6 to 7 with hydrochloric acid, and separate the organic layer; dry the organic layer over anhydrous sodium sulfate, evaporate part of the dichloromethane, and add methyl tert-butyl ether to precipitate a solid; filter, and vacuum dry the filter cake to obtain bis-p-toluenesulfonyl polyethylene glycol having the following structural formula: Wherein n is an integer from 40 to 100; Step 2: Dissolve bis(p-toluenesulfonyl)polyethylene glycol in water, add a 20% sodium methyl mercaptan aqueous solution under stirring at room temperature, and react at room temperature for 24 to 48 hours; extract the reaction solution with dichloromethane, dry the organic phase with anhydrous sodium sulfate, evaporate part of the dichloromethane, add methyl tert-butyl ether to precipitate a solid; filter, and vacuum dry the filter cake to obtain bis(methylthio)polyethylene glycol.

4. Use of the bis(methylthio)polyethylene glycol according to claim 3 as an activator in the Corey-Kim oxidation reaction, characterized in that: In step 1, the molar ratio of the polyethylene glycol, p-toluenesulfonyl chloride, and triethylamine is 1:2-3:2-3.

5. Use of the bis(methylthio)polyethylene glycol according to claim 3 as an activator in the Corey-Kim oxidation reaction, characterized in that: In step 2, the molar ratio of the bis-p-toluenesulfonyl polyethylene glycol to sodium methyl mercaptan is 1:2-4.

6. Use of bis(methylsulfinyl)polyethylene glycol as an oxidant in a Swern oxidation reaction, wherein the structure of the bis(methylsulfinyl)polyethylene glycol is: Wherein n is an integer from 40 to 100.

7. Use of the bis(methylsulfinyl)polyethylene glycol according to claim 6 as an oxidant in a Swern oxidation reaction, characterized in that: The Swern oxidation reaction is the oxidation of 2'-benzyloxycarbonyl azithromycin A to prepare 2'-benzyloxycarbonyl-4''-oxoazithromycin A or 5- O -(tert-butyldiphenylsilyl) nimoctin oxidation preparation 5- O -(tert-Butyldiphenylsilyl)-23-oxonimoctin.

8. Use of the bis(methylsulfinyl)polyethylene glycol according to claim 6 as an oxidant in a Swern oxidation reaction, characterized in that: The preparation method of the bis(methylsulfinyl)polyethylene glycol comprises the following steps: dissolving the bis(methylthio)polyethylene glycol described in claim 1 in methanol or acetonitrile, adding a 30% mass concentration of hydrogen peroxide aqueous solution, reacting at 0-35° C. for 2-4 hours, adding a saturated sodium sulfite aqueous solution to quench the reaction, distilling off the methanol or acetonitrile, and extracting with dichloromethane; drying the dichloromethane phase over anhydrous sodium sulfate, distilling off part of the dichloromethane, adding methyl tert-butyl ether to precipitate a solid; and filtering, and vacuum drying the filter cake to obtain the bis(methylsulfinyl)polyethylene glycol.

9. Use of the bis(methylsulfinyl)polyethylene glycol according to claim 8 as an oxidant in a Swern oxidation reaction, characterized in that: The molar ratio of the bis(methylthio)polyethylene glycol to hydrogen peroxide is 1:5-10.

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