Synthesis method of cyclic disulfide

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthetic method of cyclic disulfide. According to the synthetic method of the cyclic disulfide compound, dihalogenated alkane is used as a reactant, 4, 4 '-disulfanediyl bis (4-methylpentane-2-ketone) is used as a disulfide transfer reagent, and the cyclic disulfide compound is obtained under the alkaline condition. The synthesis method provided by the invention has the advantages of mild conditions, no need of additional metal and green and efficient reaction.

Description

[0001] This invention belongs to the field of organic synthesis technology and relates to a method for synthesizing cyclic disulfides. Background Technology

[0002] Cyclic disulfides are an important form of sulfur, widely distributed in proteins, natural products, pharmacologically active compounds, and materials science. Examples include lipoic acid (Int. J. Pharm. 2022, 627, 122201), which has antioxidant properties, and nereistoxin (4-N,N-dimethylamino-1,2-dithiapentane), a neurotoxin secreted by the spider nereis that is toxic to rice stem borers (Pest. Biochem. Physiol. 1975, 5, 253).

[0003] Given the importance and unique advantages of cyclic disulfide structures in pharmaceuticals and other bioactive compounds, developing universal methods for preparing cyclic disulfides suitable for synthetic purposes has been a research hotspot. Currently, typical methods for preparing acyclic disulfides are relatively mature, but the construction of cyclic disulfides remains highly challenging due to the high reactivity of sulfur-sulfur bonds. Currently, the preparation of cyclic disulfides mainly involves two routes: First, using highly reactive sodium disulfide (such as Na₂S₂ obtained from the reaction of sodium sulfide and sulfur) or tetrathiotungstate to directly convert dihalides or di-toluenesulfonates. However, this method suffers from poor selectivity and limited substrate applicability (Acta Chemica Scandinavica B. 1988, 42, 620; J. Heterocyclic Chem. 2007, 44, 521). Second, while cyclic polysulfides can be synthesized through the oxidative coupling reaction of thiols, the coupling side reactions are difficult to avoid, leading to a complex synthetic process. Functional group transfer reagents have become very popular, providing alternative retrosynthetic routes for the construction of polysulfides under mild conditions and significantly influencing reaction design in modern organic chemistry. In recent years, researchers including Harpp (J. Org. Chem. 1982, 47, 2785), Nicolaou (J. Am. Chem. Soc. 2015, 137, 8716), Jiang (Org. Chem. Front. 2021, 8, 1275), Pratt (ACS Catal. 2023, 13, 13912), Wang (ACS Catal. 2019, 9, 11426), and Xu (Org. The research teams of Wang (Angew. Chem. Int. Ed. 2023, 62, e202302199), Xian (Org. Lett. 2016, 18, 904, Studer Nat. Commun. 2022, 13, 3886) and Shang (Angew. Chem. Int. Ed. 2024, 63, e202314790) have made significant contributions. Their developed one-sided disulfide reagents have been widely applied to the synthesis of asymmetric disulfides through methods such as nucleophilic / electrophilic substitution, radical reactions, or metal / photocatalytic coupling. Progress has also been made in bilateral disulfidation reactions, for example, with reagents designed by Jiang's team based on the difference in dissociation energy of SO(N) / S-SO2R bonds (Nat. Commun. 2020, 11, 4170; Angew. Chem. Int. Ed. 2024, 63, e202408158), Fukuzawa's team using the strategy of SN bond differentiation (Angew. Chem. Int. Ed. 2023, 62, e202219156), and our team using C(sp...3 The “shearing and splicing” process of the )-SS motif demonstrates a nucleophilic bilateral disulfide reagent (DSMO) (Angew. Chem. Int. Ed. 2023, 62, e202302861) that enables the construction of straight-chain disulfide compounds. However, the synthesis of cyclic disulfides via intermolecular perthiotransfer reagents remains challenging.

[0004] Alkyl halides are an important class of organic synthetic intermediates and indispensable starting materials in many organic synthetic reactions. The synthesis of cyclic disulfides from alkyl halides under mild conditions is undoubtedly a rapid and efficient method for constructing these compounds. To address the shortcomings of current methods for cyclic disulfide synthesis, this patent aims to provide a simple method for preparing cyclic disulfides using a nucleophilic disulfide transfer reagent. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the prior art and provide a method for synthesizing cyclic disulfides, using 4,4'-dithionidinedimethylbis(4-methylpentane-2-one) as a disulfide transfer reagent and dihaloalkanes as reactants to generate cyclic disulfides through nucleophilic substitution reactions.

[0006] To achieve the above objectives, the present invention is implemented using the following technical solution:

[0007] This invention provides a method for synthesizing cyclic disulfides, comprising the following steps:

[0008] Using 4,4'-dithionidinedimethylbis(4-methylpentane-2-one) as a disulfide transfer reagent and dihaloalkanes as reactants, a nucleophilic substitution reaction occurs under basic conditions to generate cyclic disulfides.

[0009] The structural formula of the 4,4'-dithionylbis(4-methylpentan-2-one) disulfide transfer reagent is as follows:

[0010]

[0011] The structural formula of the dihaloalkane is as follows:

[0012]

[0013] Where: X 1 Independently selected from Cl, Br, I, and OMs;

[0014] X 2 Independently selected from Cl, Br, I, and OMs;

[0015] R 1 Independently selected from hydrogen, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, cyclopentyl, cyclohexyl,

[0016] R 2 Independently selected from hydrogen, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, cyclopentyl, cyclohexyl,

[0017] R 3 Independently selected from hydrogen, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, cyclopentyl, cyclohexyl,

[0018] The structural formula of the cyclic disulfide is as follows:

[0019]

[0020] Furthermore, the synthetic route for the cyclic disulfide is as follows:

[0021]

[0022] The reaction is carried out in the presence of an alkaline substance, which is an organic or inorganic base. The base is selected from any one or a combination of several of the following: sodium bicarbonate, potassium phosphate, cesium carbonate, potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, triethylamine, N,N-diisopropylethylamine, 2,6-dimethylpyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene, sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium tert-butoxide, potassium tert-butoxide, and sodium hydride. Preferably, the base is cesium carbonate.

[0023] Furthermore, the solvent is selected from one or any combination of dimethyl sulfoxide, N,N-dimethylformamide, 1,4-dioxane, tetrahydrofuran, ethyl acetate, dichloromethane, 1,2-dichloroethane, toluene, ethylbenzene, methanol, ethanol, and tert-butanol, with methanol being the preferred solvent.

[0024] Furthermore, the temperature is selected from 0 to 120°C, and preferably from 30 to 60°C.

[0025] Furthermore, the reaction time is selected from 1 to 24 hours, and the preferred reaction time is 10 hours.

[0026] Further, the molar ratio of 4,4'-dithionide dimethylbis(4-methylpentane-2-one) to dihaloalkanes is 1 to 3; preferably, the equivalent ratio is 1.5:1.

[0027] Further, the molar ratio of 4,4'-dithionedidylobis(4-methylpentane-2-one) to the base is 1 to 3, and the preferred equivalent ratio is 1:2.

[0028] Further, the solvent volume is 0.01-1M (relative to dihaloalkanes), preferably 0.2M.

[0029] Detailed Implementation of Examples

[0030] Table 1 shows the structures and yields of some representative target compounds.

[0031]

[0032]

[0033] Example 1: Compound 1 – A stir bar and cesium carbonate (0.6 mmol, 3.0 equiv.) were added to a 15 mL reaction tube, followed by three nitrogen purgings. Then, under nitrogen conditions, 4,4'-dithionidinediylbis(4-methylpentane-2-one) (0.3 mmol, 1.5 equiv.), 2-(4-propylcyclohexyl)propane-1,3-dimethyldimethylsulfonate (0.2 mmol, 1.0 equiv.), and methanol (4.0 mL) were added sequentially. The reaction was then stirred at 30 °C for 10 h. After the reaction was completed, the mixture was cooled to room temperature, extracted with water and ethyl acetate, and the organic phase was collected. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography to obtain the target compound 1 in 73% yield. 1 H NMR (600MHz, cdcl3)δ

[0034] 4.86–4.76(m,1H),4.71(s,1H),3.86(t,J=9.9Hz,1H),3.55–3.51(m,1H),3.28(s,1H),3.23(dd,J=11.8,5.6H z,1H),3.14(dd,J=11.8,3.5Hz,1H),1.85–1.79(m,1H),1.72(t,J=11.2Hz,1H),1.56(dd,J=34.2,11.3Hz,5H). 13 C NMR (151MHz, cdcl3) δ98.39,81.47,62.76,45.03,43.68,30.74,25.29,19.41.

[0035] Example 2: Compound 2 – A stir bar and cesium carbonate (0.6 mmol, 3.0 equiv.) were added to a 15 mL reaction tube, followed by three nitrogen purgings. Then, under nitrogen conditions, 4,4'-dithionidinediylbis(4-methylpentane-2-one) (0.3 mmol, 1.5 equiv.), 4-phenylbutane-1,3-dimethyldimethylsulfonate (0.2 mmol, 1.0 equiv.), and methanol (4.0 mL) were added sequentially. The reaction was then stirred at 30 °C for 10 h. After the reaction was completed, the mixture was cooled to room temperature, extracted with water and ethyl acetate, and the organic phase was collected. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography to obtain the target compound 2 in 79% yield. 1 H NMR(600MHz,cdcl3)δ7.31(t,J=7.1Hz,2H),7.23(t,J=6.5Hz,3H),3.91–3.81(m,1H),3.27–3.20(m,1H ),3.18–3.11(m,1H),2.99(d,J=7.3Hz,2H),2.41(dd,J=12.4,6.1Hz,1H),2.03(dd,J=12.9,6.6Hz,1H). 13 C NMR (151MHz, cdcl3) δ139.53,126.65,57.48,40.91,39.64,38.38.

[0036] Example 3: Compound 3 – A stir bar and cesium carbonate (0.6 mmol, 3.0 equiv.) were added to a 15 mL reaction tube, followed by three nitrogen purgings. Then, under nitrogen conditions, 4,4'-dithionidinediylbis(4-methylpentane-2-one) (0.3 mmol, 1.5 equiv.), 4-phenylpentane-1,3-dimethyldimethylsulfonate (0.2 mmol, 1.0 equiv.), and methanol (4.0 mL) were added sequentially. The reaction was then stirred at 30 °C for 10 h. After the reaction was completed, the mixture was cooled to room temperature, extracted with water and ethyl acetate, and the organic phase was collected. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography to obtain the target compound 3 in 75% yield. 1H NMR (600MHz, CDCl3) δ7.31(t,J=7.4Hz,2H),7.24(d,J=7.3Hz,3H),3.83(dd,J=15.7,8.2Hz,1H),3.28–3.10(m,2H ), 2.95 (dd, J = 8.9, 7.2Hz, 1H), 2.57 (dd, J = 12.0, 5.7Hz, 1H), 2.02 (dd, J = 12.8, 7.4Hz, 1H), 1.40 (d, J = 6.9Hz, 3H). 13 C NMR (151MHz, cdcl3) δ145.35,128.45,127.22,126.88,63.33,44.86,39.40,38.25,21.21.

[0037] Example 4: Compound 4 – A stir bar and cesium carbonate (0.6 mmol, 3.0 equiv.) were added to a 15 mL reaction tube, followed by three nitrogen purgings. Then, under nitrogen conditions, 4,4'-dithionidinediylbis(4-methylpentan-2-one) (0.3 mmol, 1.5 equiv.), ((1,3-dibromoprop-2-yl)oxy)methylbenzene (0.2 mmol, 1.0 equiv.), and methanol (4.0 mL) were added sequentially. The reaction was then stirred at 60 °C for 10 h. After the reaction was completed, the mixture was cooled to room temperature, extracted with water and ethyl acetate, and the organic phase was collected. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography to obtain the target compound 4 in 68% yield. 1 H NMR (600MHz, CDCl3) δ7.35 (q, J = 7.4Hz, 4H), 7.31 (d, J = 7.1Hz, 1H), 4.58 (s, 2H), 4.57 (d, J = 4.3Hz, 1H), 3.22 (s, 4H). 13 C NMR (151MHz, CDCl3) δ137.51,128.51,127.92,127.72,83.61,71.75,43.97.

[0038] Example 5: Compound 5 – A stir bar and cesium carbonate (0.6 mmol, 3.0 equiv.) were added to a 15 mL reaction tube, followed by three nitrogen purgings. Then, under nitrogen conditions, 4,4'-dithionidinediylbis(4-methylpentan-2-one) (0.3 mmol, 1.5 equiv.), 2-((1,3-dibromoprop-2-yl)oxy)tetrahydro-2H-pyran (0.2 mmol, 1.0 equiv.), and methanol (4.0 mL) were added sequentially. The reaction was then stirred at 60 °C for 10 h. After the reaction was complete, the mixture was cooled to room temperature, extracted with water and ethyl acetate, and the organic phase was collected. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography to obtain the target compound 5 in 74% yield. 1 H NMR(600MHz,cdcl3)δ4.86–4.76(m,1H),4.71(s,1H),3.86(t,J=9.9Hz,1H),3.55–3.51(m,1H),3.28(s,1H),3.23(dd,J= 11.8,5.6Hz,1H),3.14(dd,J=11.8,3.5Hz,1H),1.85–1.79(m,1H),1.72(t,J=11.2Hz,1H),1.56(dd,J=34.2,11.3Hz,5H). 13 C NMR (151MHz, cdcl3) δ98.39,81.47,62.76,45.03,43.68,30.74,25.29,19.41.

[0039] Example 6: Compound 6 – A stir bar and cesium carbonate (0.6 mmol, 3.0 equiv.) were added to a 15 mL reaction tube, followed by three nitrogen purgings. Then, under nitrogen conditions, 4,4'-dithionidinediylbis(4-methylpentane-2-one) (0.3 mmol, 1.5 equiv.), 2-ethylhexane-1,3-dimethyldimethylsulfonate or 4-iodo-3-(iodomethyl)heptane (0.2 mmol, 1.0 equiv.), and methanol (4.0 mL) were added sequentially. The reaction was then stirred at 30 °C for 10 h. After the reaction was completed, the mixture was cooled to room temperature, extracted with water and ethyl acetate, and the organic phase was collected. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was then purified by column chromatography to obtain the target compound 6 in yield of 81% or 78%. 1H NMR (600MHz, CDCl3) δ3.26 (dd, J=11.3, 6.2Hz, 1H), 3.18 (dt, J=9.7, 4.8Hz, 1H), 2.86 (dd, J=11.3, 6.4Hz,1H),2.10–2.01(m,1H),1.69–1.47(m,4H),1.45–1.34(m,2H),0.95(dt,J=23.3,7.4Hz,6H). 13 C HMRδ60.80,55.00,44.56,37.81,26.58,22.32,13.87,12.68.

[0040] Example 7: Compound 7 – A stir bar and cesium carbonate (0.6 mmol, 3.0 equiv.) were added to a 15 mL reaction tube, followed by three nitrogen purgings. Then, under nitrogen conditions, 4,4'-dithionidinediylbis(4-methylpentane-2-one) (0.3 mmol, 1.5 equiv.), 2-(4-methoxybenzyl)butane-1,3-dimethyldimethylsulfonate (0.2 mmol, 1.0 equiv.), and methanol (4.0 mL) were added sequentially. The reaction was then stirred at 30 °C for 10 h. After the reaction was completed, the mixture was cooled to room temperature, extracted with water and ethyl acetate, and the organic phase was collected. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography to obtain the target compound 7 in 65% yield. 1 H NMR(600MHz,cdcl3)δ7.11(d,J=7.8Hz,2H),6.84(d,J=8.0Hz,2H),3.79(s,3H),3.67(s,1H),3.19–3 .11(m,1H),2.91–2.84(m,1H),2.78(d,J=12.6Hz,2H),2.68(d,J=8.7Hz,1H),1.41(d,J=6.6Hz,3H). 13 CNMR(151MHz,cdcl3)δ158.21,131.88,129.59,114.04,55.22,54.08,51.55,39.52,34.19,15.41.

[0041] Example 8: Compound 8 – A stir bar and cesium carbonate (0.6 mmol, 3.0 equiv.) were added to a 15 mL reaction tube, followed by three nitrogen purgings. Then, under nitrogen conditions, 4,4'-dithionididiylbis(4-methylpentan-2-one) (0.3 mmol, 1.5 equiv.), 5,5-bis(bromomethyl)-2,2-dimethyl-1,3-dioxane (0.2 mmol, 1.0 equiv.), and methanol (4.0 mL) were added sequentially. The reaction was then stirred at 30 °C for 10 h. After the reaction was complete, the mixture was cooled to room temperature, extracted with water and ethyl acetate, and the organic phase was collected. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography to obtain the target compound 8 in 81% yield. 1 H NMR(600MHz,cdcl3)δ3.78(s,4H),3.00(s,4H),1.43(s,6H). 13 C NMR (151MHz, cdcl3) δ98.41,66.97,50.30,45.04,23.64.

[0042] Example 9: Compound 9 – A stir bar and cesium carbonate (0.6 mmol, 3.0 equiv.) were added to a 15 mL reaction tube, followed by three nitrogen purgings. Then, under nitrogen conditions, 4,4'-dithionididiylbis(4-methylpentane-2-one) (0.3 mmol, 1.5 equiv.), 5,5-bis(bromomethyl)-2-(4-bromophenyl)-1,3-dioxane (0.2 mmol, 1.0 equiv.), and methanol (4.0 mL) were added sequentially. The reaction was then stirred at 30 °C for 10 h. After the reaction was complete, the mixture was cooled to room temperature, extracted with water and ethyl acetate, and the organic phase was collected. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography to obtain the target compound 9 in 80% yield. 1 HNMR(600MHz,cdcl3)δ7.51(d,J=8.2Hz,2H),7.35(d,J=8.4Hz,2H),5.45(s,1 H), 4.10 (d, J = 11.0Hz, 2H), 3.86 (d, J = 11.0Hz, 2H), 3.44 (s, 2H), 2.69 (s, 2H). 13 C NMR (151MHz, cdcl3) δ136.62,131.45,127.78,123.20,101.15,73.81,50.13,47.33,42.64.

[0043] Example 10: Compound 10 – A stir bar and cesium carbonate (0.6 mmol, 3.0 equiv.) were added to a 15 mL reaction tube, followed by three nitrogen purgings. Then, under nitrogen conditions, 4,4'-dithiodiylbis(4-methylpentan-2-one) (0.3 mmol, 1.5 equiv.), 3,3-bis(bromomethyl)-3,4-dihydro-2H-thieno[3,4-b][1,4]dioxane (0.2 mmol, 1.0 equiv.), and methanol (4.0 mL) were added sequentially. The reaction was then stirred at 60 °C for 10 h. After the reaction was completed, the mixture was cooled to room temperature, extracted with water and ethyl acetate, and the organic phase was collected. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain the crude product. The crude product was then purified by column chromatography to obtain the target compound 10 in 78% yield. 1 H NMR (600MHz, cdcl3) δ6.49 (d, J = 4.5 Hz, 2H), 4.10 (d, J = 4.5 Hz, 4H), 3.61 (d, J = 4.5 Hz, 4H). 13 CNMR(151MHz,cdcl3)δ148.63,105.73,74.14,46.16,34.41.

[0044] Example 11: Compound 11 – A stir bar and cesium carbonate (0.6 mmol, 3.0 equiv.) were added to a 15 mL reaction tube, followed by three nitrogen purgings. Then, under nitrogen conditions, 4,4'-dithionidinediylbis(4-methylpentan-2-one) (0.3 mmol, 1.5 equiv.), 1,1-dibromo-2,2-bis(chloromethyl)cyclopropane (0.2 mmol, 1.0 equiv.), and methanol (4.0 mL) were added sequentially. The reaction was then stirred at 60 °C for 10 h. After the reaction was completed, the mixture was cooled to room temperature, extracted with water and ethyl acetate, and the organic phase was collected. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography to obtain the target compound 11 in 78% yield. 1 H NMR (600MHz, CDCl3) δ3.64 (d, J = 11.9 Hz, 2H), 3.11 (d, J = 11.9 Hz, 2H), 1.92 (s, 2H). 13 C NMR (151MHz, CDCl3) δ47.67, 36.21, 32.84.

[0045] Example 12: Compound 12 – A stir bar and cesium carbonate (0.6 mmol, 3.0 equiv.) were added to a 15 mL reaction tube, followed by three nitrogen purgings. Then, under nitrogen conditions, 4,4'-dithionidinediylbis(4-methylpentane-2-one) (0.3 mmol, 1.5 equiv.), 2,2-bis(bromomethyl)propane-1,3-diol (0.2 mmol, 1.0 equiv.), and methanol (4.0 mL) were added sequentially. The reaction was then stirred at 60 °C for 10 h. After the reaction was complete, the mixture was cooled to room temperature, extracted with water and ethyl acetate, and the organic phase was collected. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure to obtain the crude product. This crude product was then purified by column chromatography to obtain the target compound 12 in 65% yield. 1 H NMR (600MHz, DMSO) δ4.84 (s, 2H), 3.39 (d, J = 5.3Hz, 4H), 2.88 (s, 4H). 13 C NMR (151MHz, DMSO) δ62.96, 58.66, 43.65.

[0046] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any simple modifications, equivalent changes, and alterations made to the above embodiments without departing from the technical essence of the present invention shall still fall within the scope of the technical solution of the present invention.

Claims

1. A method for synthesizing cyclic disulfides, characterized in that, Using 4,4'-dithionidinedimethylbis(4-methylpentan-2-one) as a disulfide transfer reagent and dihaloalkanes as reactants, cyclic disulfides are generated through nucleophilic substitution reactions; The structural formula of the 4,4'-dithionylbis(4-methylpentan-2-one) disulfide transfer reagent is as follows: The structural formula of the dihaloalkane is as follows: Where: X 1 Independently selected from Cl, Br, I, and OMs; X 2 Independently selected from Cl, Br, I, and OMs; R 1 Independently selected from hydrogen, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, cyclopentyl, cyclohexyl, R 2 Independently selected from hydrogen, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, cyclopentyl, cyclohexyl, R 3 Independently selected from hydrogen, methyl, ethyl, n-propyl, sec-propyl, n-butyl, sec-butyl, isobutyl, cyclopentyl, cyclohexyl, The structural formula of the method for synthesizing the cyclic disulfide is as follows:

2. The method for synthesizing cyclic disulfides according to claim 1, characterized in that, The synthetic route is as follows:

3. The method for synthesizing cyclic disulfides as described in claim 2, characterized in that, The base in the synthesis reaction is any one or a combination of several of the following: sodium bicarbonate, potassium phosphate, cesium carbonate, potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, triethylamine, N,N-diisopropylethylamine, 2,6-dimethylpyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene, sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium tert-butoxide, potassium tert-butoxide, and sodium hydride.

4. The method for synthesizing cyclic disulfides as described in claim 2, characterized in that, The solvent used in the synthesis reaction is one or any combination of dimethyl sulfoxide, N,N-dimethylformamide, 1,4-dioxane, tetrahydrofuran, ethyl acetate, dichloromethane, 1,2-dichloroethane, toluene, ethylbenzene, methanol, ethanol, and tert-butanol.

5. The method for synthesizing cyclic disulfides as described in claim 2, characterized in that, The reaction temperature in the synthesis reaction is 0–120 °C.

6. The method for synthesizing cyclic disulfides as described in claim 2, characterized in that, The reaction time in the synthesis reaction is 1 to 24 hours.

7. The method for synthesizing cyclic disulfides as described in claim 2, characterized in that, The molar ratio of 4,4'-dithionedidylbis(4-methylpentan-2-one) to dihaloalkanes in the general formula is 1 to 3; the molar ratio of 4,4'-dithionedidylbis(4-methylpentan-2-one) to base is 1 to 3, and the solvent volume is 0.01 to 1 M (relative to dihaloalkanes).

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