Asymmetric dithioalkane and preparation method thereof

Abstract

The invention discloses asymmetric dithioalkane and a preparation method thereof, the structural general formula of the asymmetric dithioalkane is # imgabs0 #, and R is an electron donating group or an electron withdrawing group; the preparation method comprises the following steps: (1) stirring a thiophenol raw material and an organic solvent for reaction; (2) adding into water, extracting, collecting, drying, and carrying out reduced pressure distillation; and (3) separating and purifying. The asymmetric dithioalkane shows better site selectivity and reaction activity, and the preparation method has the advantages of single substrate (thiophenol), mild reaction conditions (room temperature), no catalyst, no metal, no alkali, mild conditions (triggered by visible light), safe reaction route, environmental protection, simple conditions, simple operation (one-step synthesis) and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and more particularly to an asymmetric disulfane and a preparation method thereof. Background Art

[0002] As a core molecular skeleton, disulfane widely exists in various drugs, natural products, rubber additives, polymers, and bioactive molecules (as shown in Figure 1 ). At the same time, disulfane can also be used as a photocatalyst, hydrogen atom transfer (HAT) catalyst, cocatalyst or initiator in organic synthesis or polymerization reactions, such as cyclization, anti-Markovnikov addition, aromatic olefin carbonylation reaction, isomerization, etc. Therefore, the synthesis research of disulfane has always been the focus of organic sulfur chemistry.

[0003] As a kind of the above-mentioned disulfane, asymmetric disulfane has received more and more attention due to its asymmetric and variable structure, which endows it with more unique properties in many fields. So far, there are many different methods for preparing symmetrical disulfane, but due to the rapid thiol-disulfane exchange reaction, most of these methods are not applicable to the synthesis of asymmetric disulfane. For the synthesis of asymmetric disulfane, the main synthesis methods reported in the mature processes and literature include:

[0004] (1) Oxidation method: 1) Oxidizing mixed thiols with an excessive amount of oxidants (iodine, peroxide, dichlorodicyanoquinone, metal oxides, etc.) (Musiejuk M, Witt D. Recent developments in the synthesis of unsymmetrical disulfanes (disulfides). A review [J]. Organic Preparations and Procedures International, 2015, 47(2): 95-131.); 2) Base-catalyzed aerobic oxidation of different thiols: Different thiols achieve dehydrogenative cross-coupling under the catalysis of a base, thereby realizing the synthesis of asymmetric disulfane (Qiu X, Yang X, Zhang Y, et al. Efficient and practical synthesis of unsymmetrical disulfides via base-catalyzed aerobic oxidative dehydrogenative coupling of thiols [J]. Organic Chemistry Frontiers, 2019, 6(13): 2220-2225);

[0005] (2) Thiol and symmetrical disulfane exchange method: In the presence of catalysts such as rhodium metal, the synthesis of unsymmetrical disulfane is achieved by the exchange method of thiol and symmetrical disulfane (Musiejuk M, Witt D. Recent developments in the synthesis of unsymmetrical disulfanes (disulfides). A review [J]. Organic Preparations and Procedures International, 2015, 47(2): 95 - 131.);

[0006] (3) Thioalkylation - thiolysis of thiol: At low temperature, the synthesis of unsymmetrical disulfane is achieved by the thioalkylation of thiol with electrophilic sulfoxide derivatives, or by replacing the appropriate leaving group on the sulfoxide compound using thiol or thiolate anion through a nucleophilic SN2 reaction (Musiejuk M, Witt D. Recent developments in the synthesis of unsymmetrical disulfanes (disulfides). A review [J]. Organic Preparations and Procedures International, 2015, 47(2): 95 - 131.).

[0007] Summarizing the existing synthesis methods of unsymmetrical disulfides, it is not difficult to see that most of the above - mentioned relatively mature and widely used synthesis methods of unsymmetrical disulfane require various thiols or symmetrical disulfides as raw materials and are achieved under the intervention of conditions such as metals, oxidants or acids, bases, etc. Therefore, the existing problems are:

[0008] (1) The use of catalysts and oxidants (acids, bases, metal salts, etc.);

[0009] (2) The existence of a mixture of symmetrical disulfane and unsymmetrical disulfane, which is difficult to separate and purify;

[0010] (3) Harsh reaction conditions (low temperature, some nucleophilic reagent intermediates are cumbersome to prepare, toxic, expensive, and seriously corrode equipment), cumbersome operation, environmental pollution, etc.

[0011] Therefore, how to synthesize unsymmetrical disulfane under mild conditions (without catalysts, without metals, without bases) is an urgent problem to be solved by those skilled in the art. SUMMARY OF THE INVENTION

[0012] In view of this, the purpose of the present invention is to provide an unsymmetrical disulfane and its preparation method to solve the deficiencies in the prior art.

[0013] To achieve the above object, the present invention adopts the following technical solutions:

[0014] An asymmetric disulfide, with the structural general formula:

[0015] Wherein,

[0016] R is an electron-donating group or an electron-withdrawing group.

[0017] Further, the above electron-donating groups are Me, MeO or t-Bu; the electron-withdrawing groups are F, Cl or Br.

[0018] Further, the substitution mode of the above R is mono-substitution, di-substitution and tri-substitution.

[0019] Furthermore, the position of the above mono-substitution is ortho-position, meta-position and para-position; the positions of the di-substitution are 2,4-substitution, 2,5-substitution, 2,6-substitution, 3,4-substitution and 3,5-substitution; the position of the tri-substitution is 2,4,5-substitution.

[0020] Further, the above asymmetric disulfide is 1-(4-methyl-2-(p-methylthiophenyl)phenyl)-2-(p-tolyl)disulfide 1-(4-fluoro-2-(p-fluorothiophenyl)phenyl)-2-(p-fluorophenyl)disulfide 1-(2-methyl-6-(2-methylthiophenyl)phenyl)-2-(2-methylthiophenyl)disulfide 1-(2-methoxy-6-(2-methoxythiophenyl)phenyl)-2-(2-methoxythiophenyl)disulfide 1-(2-chloro-6-(2-chlorothiophenyl)phenyl)-2-(2-chlorothiophenyl)disulfide 1-(2-bromo-6-(2-bromothiophenyl)phenyl)-2-(2-bromothiophenyl)disulfide 1-(2,4-dimethyl-6-(2,4-dimethylthiophenyl)phenyl)-2-(2,4-dimethylphenyl)disulfide 1-(4-fluoro-6-chloro-2-(2-chloro-4-fluorothiophenyl)phenyl)-2-(2-chloro-4-fluorophenyl)disulfide 1-(4,6-dichloro-2-(2,4-dichlorothiophenyl)phenyl)-2-(2,4-dichlorophenyl)disulfide 1-(2,5-dimethyl-6-(2,5-dimethylthiophenyl)phenyl)-2-(2,5-dimethylphenyl)disulfide 1-(2,6-dimethyl-4-(2,6-dimethylthiophenyl)phenyl)-2-(2,6-dimethylphenyl)disulfide 1-(4,5-dichloro-2-(3,4-dichlorothiophenyl)phenyl)-2-(3,4-dichlorophenyl)disulfane 1-(3,5-dimethyl-2-(3,5-dimethylthiophenyl)phenyl)-2-(3,5-dimethylphenyl)disulfane 1-(3,4,6-trichloro-2-(2,4,5-trichlorothiophenyl)phenyl)-2-(2,4,5-trichlorophenyl)disulfane or 1-(2-thienyl)thiophen-2-yl disulfane

[0021]

[0022] A preparation method of the above-mentioned asymmetric disulfane, and the reaction formula is as follows:

[0023]

[0024] Specifically, it includes the following steps:

[0025] (1) Stir and react the thiophenol raw material and the organic solvent (monitor the reaction end point by TLC) to obtain a mixture;

[0026] (2) Add the mixture into water, extract it three times with dichloromethane, collect the organic phase, then dry it and distill off the organic solvent under reduced pressure to obtain a crude product;

[0027] (3) Separate and purify the crude product by silica gel column chromatography to obtain the asymmetric disulfane.

[0028] Furthermore, in the above step (1), the structural formula of the thiophenol raw material is: wherein, R is an electron-donating group or an electron-withdrawing group.

[0029] Furthermore, the above electron-donating group is Me, MeO or t-Bu; the electron-withdrawing group is F, Cl or Br.

[0030] Furthermore, the substitution mode of the above R is monosubstitution, disubstitution and trisubstitution.

[0031] Even further, the position of the above monosubstitution is ortho, meta and para; the positions of the disubstitution are 2,4-substitution, 2,5-substitution, 2,6-substitution, 3,4-substitution and 3,5-substitution; the position of the trisubstitution is 2,4,5-substitution.

[0032] Furthermore, in the above step (1), the thiophenol raw material is p-methylbenzenethiol p-fluorobenzenethiol 2-methylbenzenethiol 2-methoxybenzenethiol 2-chlorobenzenethiol 2-Bromobenzenethiol 2,4-Dimethylbenzenethiol 2-Chloro-4-fluorobenzenethiol 2,4-Dichlorobenzenethiol 2,5-Dimethylbenzenethiol 2,6-Dimethylbenzenethiol 3,4-Dichlorobenzenethiol 3,5-Dimethylbenzenethiol 2,4,5-Trichlorobenzenethiol and 2-Thiophenethiol

[0033] Furthermore, in the above step (1), the organic solvent is dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), ethanol (EtOH), 1,4-dioxane or ethyl acetate (EtOAc), preferably dimethyl sulfoxide (DMSO); the conditions for the stirring reaction are room temperature (30 °C) and light; the reaction concentration for the stirring reaction is 0.1 - 2.0 M, preferably 0.1 M, 0.2 M, 0.5 M, 1.0 M or 2.0 M, more preferably 0.5 M;; the reaction time for the stirring reaction is 27 - 36 h; the light source for the light is purple LED, blue LED, green LED, white LED or ambient light, preferably purple LED.

[0034] From the above technical solutions, it can be seen that compared with the prior art, the beneficial effects of the present invention are as follows:

[0035] 1. The asymmetric dithiane of the present invention exhibits good site selectivity and reactivity, that is, different asymmetric dithianes can be selectively generated according to different substituents. For example, when comparing Example 11 with other examples, when there is an ortho reaction site in the reaction, the ortho product is mainly formed; moreover, compared with the method of oxidizing mixed thiols in the prior art, the preparation method of the present invention is relatively controllable.

[0036] 2. The preparation method of the asymmetric dithiane of the present invention has the advantages of using a single substrate (benzenethiol), mild reaction conditions (room temperature), no catalyst, no metal, no base, mild conditions (initiated by visible light), safe and environmentally friendly reaction route, simple conditions, and easy operation (one-step synthesis). Brief Description of the Drawings

[0037] Figure 1 It is a structural formula diagram of dithiane as the core molecular skeleton;

[0038] Figure 2 It is a single crystal structure diagram of the product of Example 1. Detailed Description of the Invention

[0039] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0040] Example 1

[0041] 1-(4-Methyl-2-(p-methylthiophenyl)phenyl)-2-(p-tolyl)disulfane, the structural formula is:

[0042]

[0043] The preparation method of the above 1-(4-Methyl-2-(p-methylthiophenyl)phenyl)-2-(p-tolyl)disulfane specifically includes the following steps:

[0044] (1) Put p-methylthiophenol into a 10 mL round-bottom flask, inject the organic solvent dimethyl sulfoxide (DMSO) to make the system concentration 0.5 M, and then react under a purple LED at 30 °C and a wavelength of 396 nm for 27 h. Monitor the reaction end point by TLC to obtain a mixture;

[0045] (2) Add the mixture to water, extract it three times with dichloromethane first, collect the organic phase, then dry it and distill off the organic solvent under reduced pressure to obtain a crude product;

[0046] (3) Subject the crude product to silica gel column chromatography and elute it with an eluent (petroleum ether) to obtain a white solid, which is the product 1-(4-Methyl-2-(p-methylthiophenyl)phenyl)-2-(p-tolyl)disulfane.

[0047] Example 2

[0048] 1-(4-Fluoro-2-(p-fluorothiophenyl)phenyl)-2-(p-fluorophenyl)disulfane, the structural formula is:

[0049]

[0050] The preparation method of the above 1-(4-Fluoro-2-(p-fluorothiophenyl)phenyl)-2-(p-fluorophenyl)disulfane specifically includes the following steps:

[0051] (1) Put p-fluorothiophenol into a 10 mL round-bottom flask, inject the organic solvent dimethyl sulfoxide (DMSO) to make the system concentration 0.5 M, and then react under a purple LED at 30 °C and a wavelength of 396 nm for 27 h. Monitor the reaction end point by TLC to obtain a mixture;

[0052] (2) Add the mixture to water, extract it three times with dichloromethane, collect the organic phase, then dry it and remove the organic solvent by distillation under reduced pressure to obtain the crude product;

[0053] (3) Subject the crude product to silica gel column chromatography and elute it with an eluent (petroleum ether) to obtain a yellow oil, which is the product 1-(4-fluoro-2-(p-fluorothiophenyl)phenyl)-2-(p-fluorophenyl)disulfane.

[0054] Example 3

[0055] 1-(2-Methyl-6-(2-methylthiophenyl)phenyl)-2-(2-methylthiophenyl)disulfane, with the structural formula:

[0056]

[0057] The preparation method of the above 1-(2-methyl-6-(2-methylthiophenyl)phenyl)-2-(2-methylthiophenyl)disulfane specifically includes the following steps:

[0058] (1) Put p-2-methylthiophenol into a 10 mL round-bottom flask, inject the organic solvent dimethyl sulfoxide (DMSO) to make the system concentration 0.5 M, then react under a purple LED at 30 °C and a wavelength of 396 nm for 27 h, monitor the reaction end point by TLC to obtain a mixture;

[0059] (2) Add the mixture to water, extract it three times with dichloromethane, collect the organic phase, then dry it and remove the organic solvent by distillation under reduced pressure to obtain the crude product;

[0060] (3) Subject the crude product to silica gel column chromatography and elute it with an eluent (petroleum ether) to obtain a white solid, which is the product 1-(2-methyl-6-(2-methylthiophenyl)phenyl)-2-(2-methylthiophenyl)disulfane.

[0061] Example 4

[0062] 1-(2-Methoxy-6-(2-methoxythiophenyl)phenyl)-2-(2-methoxythiophenyl)disulfane, with the structural formula:

[0063]

[0064] The preparation method of the above 1-(2-methoxy-6-(2-methoxythiophenyl)phenyl)-2-(2-methoxythiophenyl)disulfane specifically includes the following steps:

[0065] (1) Put 2-methoxythiophenol Place it in a 10 mL round-bottom flask, and inject the organic solvent dimethyl sulfoxide (DMSO) to make the system concentration 0.5 M. Then react under a purple LED at 30 °C and a wavelength of 396 nm for 27 h, monitor the reaction end point by TLC to obtain a mixture;

[0066] (2) Add the mixture to water, extract it three times with dichloromethane first, collect the organic phase, then dry it and remove the organic solvent by distillation under reduced pressure to obtain a crude product;

[0067] (3) Subject the crude product to silica gel column chromatography and elute it with an eluent (petroleum ether / ethyl acetate (40 / 1, v / v)) to obtain a white solid, which is the product 1-(2-methoxy-6-(2-methoxythiophenyl)phenyl)-2-(2-methoxythiophenyl)disulfane.

[0068] Example 5

[0069] 1-(2-Chloro-6-(2-chlorothiophenyl)phenyl)-2-(2-chlorothiophenyl)disulfane, the structural formula is:

[0070]

[0071] The preparation method of the above 1-(2-chloro-6-(2-chlorothiophenyl)phenyl)-2-(2-chlorothiophenyl)disulfane specifically includes the following steps:

[0072] (1) Place 2-chlorobenzenethiol in a 10 mL round-bottom flask, inject the organic solvent dimethyl sulfoxide (DMSO) to make the system concentration 0.5 M. Then react under a purple LED at 30 °C and a wavelength of 396 nm for 27 h, monitor the reaction end point by TLC to obtain a mixture;

[0073] (2) Add the mixture to water, extract it three times with dichloromethane first, collect the organic phase, then dry it and remove the organic solvent by distillation under reduced pressure to obtain a crude product;

[0074] (3) Subject the crude product to silica gel column chromatography and elute it with an eluent (petroleum ether) to obtain a white solid, which is the product 1-(2-chloro-6-(2-chlorothiophenyl)phenyl)-2-(2-chlorothiophenyl)disulfane.

[0075] Example 6

[0076] 1-(2-Bromo-6-(2-bromothiophenyl)phenyl)-2-(2-bromothiophenyl)disulfane, the structural formula is:

[0077]

[0078] The preparation method of the above 1-(2-bromo-6-(2-bromothiophenyl)phenyl)-2-(2-bromothiophenyl)disulfane specifically includes the following steps:

[0079] (1) Put 2-bromobenzenethiol into a 10 mL round-bottom flask, inject the organic solvent dimethyl sulfoxide (DMSO) to make the system concentration 0.5 M, and then react under a purple LED at 30 °C and a wavelength of 396 nm for 29 h. Monitor the reaction end point by TLC to obtain a mixture;

[0080] (2) Add the mixture to water, extract it three times with dichloromethane, collect the organic phase, then dry it and distill off the organic solvent under reduced pressure to obtain a crude product;

[0081] (3) Subject the crude product to silica gel column chromatography and elute it with an eluent (petroleum ether) to obtain a white solid, which is the product 1-(2-bromo-6-(2-bromothiophenyl)phenyl)-2-(2-bromothiophenyl)disulfane.

[0082] Example 7

[0083] 1-(2,4-dimethyl-6-(2,4-dimethylthiophenyl)phenyl)-2-(2,4-dimethylphenyl)disulfane, the structural formula is:

[0084]

[0085] The preparation method of the above 1-(2,4-dimethyl-6-(2,4-dimethylthiophenyl)phenyl)-2-(2,4-dimethylphenyl)disulfane specifically includes the following steps:

[0086] (1) Put p-2,4-dimethylbenzenethiol into a 10 mL round-bottom flask, inject the organic solvent dimethyl sulfoxide (DMSO) to make the system concentration 0.5 M, and then react under a purple LED at 30 °C and a wavelength of 396 nm for 27 h. Monitor the reaction end point by TLC to obtain a mixture;

[0087] (2) Add the mixture to water, extract it three times with dichloromethane, collect the organic phase, then dry it and distill off the organic solvent under reduced pressure to obtain a crude product;

[0088] (3) Subject the crude product to silica gel column chromatography and elute it with an eluent (petroleum ether) to obtain a white solid, which is the product 1-(2,4-dimethyl-6-(2,4-dimethylthiophenyl)phenyl)-2-(2,4-dimethylphenyl)disulfane.

[0089] Example 8

[0090] 1-(4-Fluoro-6-chloro-2-(2-chloro-4-fluorothiophenyl)phenyl)-2-(2-chloro-4-fluorophenyl)disulfane, with the structural formula as follows:

[0091]

[0092] The preparation method of the above 1-(4-Fluoro-6-chloro-2-(2-chloro-4-fluorothiophenyl)phenyl)-2-(2-chloro-4-fluorophenyl)disulfane specifically includes the following steps:

[0093] (1) Put 2-chloro-4-fluorobenzenethiol into a 10 mL round-bottom flask, inject the organic solvent dimethyl sulfoxide (DMSO) to make the system concentration 0.5 M, then react under a purple LED at 30 °C and a wavelength of 396 nm for 28 h, monitor the reaction end point by TLC to obtain a mixture;

[0094] (2) Add the mixture to water, extract it three times with dichloromethane first, collect the organic phase, then dry it and distill off the organic solvent under reduced pressure to obtain a crude product;

[0095] (3) Subject the crude product to silica gel column chromatography and elute it with an eluent (petroleum ether) to obtain a white solid, which is the product 1-(4-Fluoro-6-chloro-2-(2-chloro-4-fluorothiophenyl)phenyl)-2-(2-chloro-4-fluorophenyl)disulfane.

[0096] Example 9

[0097] 1-(4,6-Dichloro-2-(2,4-dichlorothiophenyl)phenyl)-2-(2,4-dichlorophenyl)disulfane, with the structural formula as follows:

[0098]

[0099] The preparation method of the above 1-(4,6-Dichloro-2-(2,4-dichlorothiophenyl)phenyl)-2-(2,4-dichlorophenyl)disulfane specifically includes the following steps:

[0100] (1) Put 2,4-dichlorobenzenethiol into a 10 mL round-bottom flask, inject the organic solvent dimethyl sulfoxide (DMSO) to make the system concentration 0.5 M, then react under a purple LED at 30 °C and a wavelength of 396 nm for 30 h, monitor the reaction end point by TLC to obtain a mixture;

[0101] (2) Add the mixture to water, extract it three times with dichloromethane first, collect the organic phase, then dry it and distill off the organic solvent under reduced pressure to obtain a crude product;

[0102] (3) The crude product was subjected to silica gel column chromatography and eluted with an eluent (petroleum ether) to obtain a white solid, which was the product 1-(4,6-dichloro-2-(2,4-dichlorothiophenyl)phenyl)-2-(2,4-dichlorophenyl)disulfane.

[0103] Example 10

[0104] 1-(2,5-Dimethyl-6-(2,5-dimethylthiophenyl)phenyl)-2-(2,5-dimethylphenyl)disulfane, with the structural formula:

[0105]

[0106] The preparation method of the above 1-(2,5-dimethyl-6-(2,5-dimethylthiophenyl)phenyl)-2-(2,5-dimethylphenyl)disulfane specifically includes the following steps:

[0107] (1) 2,5-Dimethylbenzenethiol was put into a 10 mL round-bottom flask, and an organic solvent dimethyl sulfoxide (DMSO) was injected to make the system concentration 0.5 M. Then, the reaction was carried out under a purple LED at 30 °C and a wavelength of 396 nm for 30 h. The reaction end point was monitored by TLC to obtain a mixture.

[0108] (2) The mixture was added to water, extracted three times with dichloromethane, the organic phase was collected, then dried and the organic solvent was removed by reduced pressure distillation to obtain a crude product;

[0109] (3) The crude product was subjected to silica gel column chromatography and eluted with an eluent (petroleum ether) to obtain a white solid, which was the product 1-(2,5-dimethyl-6-(2,5-dimethylthiophenyl)phenyl)-2-(2,5-dimethylphenyl)disulfane.

[0110] Example 11

[0111] 1-(2,6-Dimethyl-4-(2,6-dimethylthiophenyl)phenyl)-2-(2,6-dimethylphenyl)disulfane, with the structural formula:

[0112]

[0113] The preparation method of the above 1-(2,6-dimethyl-4-(2,6-dimethylthiophenyl)phenyl)-2-(2,6-dimethylphenyl)disulfane specifically includes the following steps:

[0114] (1) 2,6-Dimethylbenzenethiol Put it into a 10 mL round-bottom flask, inject the organic solvent dimethyl sulfoxide (DMSO) to make the system concentration 0.5 M, then react under a purple LED at 30 °C and a wavelength of 396 nm for 32 h. Monitor the reaction end point by TLC to obtain a mixture;

[0115] (2) Add the mixture to water, extract it three times with dichloromethane first, collect the organic phase, then dry it and distill off the organic solvent under reduced pressure to obtain a crude product;

[0116] (3) Subject the crude product to silica gel column chromatography and elute it with an eluent (petroleum ether) to obtain a white solid, which is the product 1-(2,6-dimethyl-4-(2,6-dimethylthiophenyl)phenyl)-2-(2,6-dimethylphenyl)disulfane.

[0117] Example 12

[0118] 1-(4,5-dichloro-2-(3,4-dichlorothiophenyl)phenyl)-2-(3,4-dichlorophenyl)disulfane, and its structural formula is:

[0119]

[0120] The preparation method of the above 1-(4,5-dichloro-2-(3,4-dichlorothiophenyl)phenyl)-2-(3,4-dichlorophenyl)disulfane specifically includes the following steps:

[0121] (1) Put 3,4-dichlorobenzenethiol into a 10 mL round-bottom flask, inject the organic solvent dimethyl sulfoxide (DMSO) to make the system concentration 0.5 M, then react under a purple LED at 30 °C and a wavelength of 396 nm for 31 h. Monitor the reaction end point by TLC to obtain a mixture;

[0122] (2) Add the mixture to water, extract it three times with dichloromethane first, collect the organic phase, then dry it and distill off the organic solvent under reduced pressure to obtain a crude product;

[0123] (3) Subject the crude product to silica gel column chromatography and elute it with an eluent (petroleum ether) to obtain a white solid, which is the product 1-(4,5-dichloro-2-(3,4-dichlorothiophenyl)phenyl)-2-(3,4-dichlorophenyl)disulfane.

[0124] Example 13

[0125] 1-(3,5-dimethyl-2-(3,5-dimethylthiophenyl)phenyl)-2-(3,5-dimethylphenyl)disulfane, and its structural formula is:

[0126]

[0127] The preparation method of the above-mentioned 1-(3,5-dimethyl-2-(3,5-dimethylthiophenyl)phenyl)-2-(3,5-dimethylphenyl)disulfane specifically comprises the following steps:

[0128] (1) Put 3,5-dimethylbenzenethiol into a 10 mL round-bottom flask, inject the organic solvent dimethyl sulfoxide (DMSO) to make the system concentration 0.5 M, then react under a purple LED with a wavelength of 396 nm at 30 °C for 32 h, monitor the reaction end point by TLC to obtain a mixture;

[0129] (2) Add the mixture into water, extract it three times with dichloromethane first, collect the organic phase, then dry it and distill off the organic solvent under reduced pressure to obtain a crude product;

[0130] (3) Subject the crude product to silica gel column chromatography, elute it with an eluent (petroleum ether) to obtain a white solid, which is the product 1-(3,5-dimethyl-2-(3,5-dimethylthiophenyl)phenyl)-2-(3,5-dimethylphenyl)disulfane.

[0131] Example 14

[0132] 1-(3,4,6-trichloro-2-(2,4,5-trichlorothiophenyl)phenyl)-2-(2,4,5-trichlorophenyl)disulfane, the structural formula of which is:

[0133]

[0134] The preparation method of the above-mentioned 1-(3,4,6-trichloro-2-(2,4,5-trichlorothiophenyl)phenyl)-2-(2,4,5-trichlorophenyl)disulfane specifically comprises the following steps:

[0135] (1) Put 2,4,5-trichlorobenzenethiol into a 10 mL round-bottom flask, inject the organic solvent dimethyl sulfoxide (DMSO) to make the system concentration 0.5 M, then react under a purple LED with a wavelength of 396 nm at 30 °C for 30 h, monitor the reaction end point by TLC to obtain a mixture;

[0136] (2) Add the mixture into water, extract it three times with dichloromethane first, collect the organic phase, then dry it and distill off the organic solvent under reduced pressure to obtain a crude product;

[0137] (3) Subject the crude product to silica gel column chromatography, elute it with an eluent (petroleum ether) to obtain a white solid, which is the product 1-(3,4,6-trichloro-2-(2,4,5-trichlorothiophenyl)phenyl)-2-(2,4,5-trichlorophenyl)disulfane.

[0138] Example 15

[0139] 1-(2-Thienyl)thiophen-2-yl disulfide, with the structural formula:

[0140]

[0141] The preparation method of the above 1-(2-thienyl)thiophen-2-yl disulfide specifically includes the following steps:

[0142] (1) Put 2-mercaptothiophene into a 10 mL round-bottom flask, inject the organic solvent dimethyl sulfoxide (DMSO) to make the system concentration 0.5 M, and then react under a purple LED at 30 °C and a wavelength of 396 nm for 36 h. Monitor the reaction end point by TLC to obtain a mixture;

[0143] (2) Add the mixture to water, extract it three times with dichloromethane, collect the organic phase, then dry it and distill off the organic solvent under reduced pressure to obtain a crude product;

[0144] (3) Subject the crude product to silica gel column chromatography and elute it with an eluent (petroleum ether) to obtain a white solid, which is the product 1-(2-thienyl)thiophen-2-yl disulfide.

[0145] Performance test

[0146] 1. Yield

[0147] Respectively count the morphology and yield of the products in Examples 1-15. The results are shown in Table 1.

[0148] Table 1 Morphology and yield of the products in Examples 1-15

[0149]

[0150] As can be seen from Table 1, the morphology of the products prepared in Examples 1-15 meets the expectations and the yield is relatively high (up to 60%).

[0151] 2. 1 H NMR

[0152] Take the products prepared in Examples 1-15 respectively and conduct nuclear magnetic resonance ( 1 H NMR) detection. The results are shown in Table 2.

[0153] Table 2 1 H NMR of the products in Examples 1-15

[0154]

[0155]

[0156] As can be seen from Table 2, the products obtained in Examples 1-15 contain hydrogen element, and the environmental information of hydrogen atoms in the molecule based on the hydrogen nuclear magnetic resonance spectrum is given, including chemical shift, the number of hydrogen atoms, coupling constant and other information.

[0157] 3. 13 C NMR

[0158] Take the products obtained in Examples 1-15 respectively, and conduct carbon-13 nuclear magnetic resonance ( 13 C NMR) detection. The results are shown in Table 3.

[0159] Table 3 13 C NMR

[0160]

[0161]

[0162] As can be seen from Table 4, the products obtained in Examples 1-15 contain carbon element, and the environmental information of carbon atoms in the molecule based on the carbon nuclear magnetic resonance spectrum is given, including chemical shift, the number of carbon atoms, coupling constant and other information.

[0163] 4. HRMS

[0164] Take the products obtained in Examples 1-15 respectively, and conduct high resolution mass spectrometry (HRMS) detection. The results are shown in Table 4.

[0165] Table 4 HRMS of the products in Examples 1-15

[0166]

[0167]

[0168]

[0169] As can be seen from Table 4, through the high resolution mass spectrometry (HRMS) detection of the products obtained in Examples 1-15, the molecular structure of the target product is further confirmed.

[0170] 5. 19 F NMR

[0171] Take the products obtained in Examples 2 and 8 respectively, and conduct nuclear magnetic resonance fluorine spectrum ( 19 F NMR) detection. The results are shown in Table 5.

[0172] Table 5 19 F NMR

[0173]

[0174] As can be seen from Table 5, the products obtained in Example 2 and Example 8 contain fluorine elements, and the environmental information of fluorine atoms in the molecule based on the nuclear magnetic resonance fluorine spectrum is given, including chemical shift, the number of fluorine atoms, coupling constants and other information.

[0175] 6. Single crystal structure

[0176] The single crystal structure of the product of Example 1 is as Figure 2 shown.

[0177] As Figure 2 can be seen, the absolute structure of the product of Example 1 is further confirmed to be an asymmetric disulfide.

[0178] In summary: From Tables 1-5 and Figure 2 the data provided, the structure of the asymmetric disulfide is confirmed, further proving the synthetic method for preparing the asymmetric disulfide and the scope of thiophenol substrates applicable to this method.

[0179] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be obvious to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments shown herein, but will be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. An asymmetric disulfide, characterized in that, The general structural formula is: Among them, R is an electron-donating group or an electron-withdrawing group.

2. An asymmetric dithiane according to claim 1, characterized in that, The electron-donating group is Me, MeO or t-Bu; the electron-withdrawing group is F, Cl or Br.

3. An asymmetric disulfide according to claim 1, wherein The substitution pattern of R is mono-substitution, di-substitution and tri-substitution.

4. An asymmetric disulfide according to claim 3, characterized in that, The position of the mono-substitution is ortho, meta and para; the positions of the di-substitution are 2,4-substitution, 2,5-substitution, 2,6-substitution, 3,4-substitution and 3,5-substitution; the position of the tri-substitution is 2,4,5-substitution.

5. A method for preparing the asymmetric disulfide as claimed in claim 1, characterized in that, Specifically, it includes the following steps: (1) Stir and react a thiophenol raw material and an organic solvent to obtain a mixture. (2) Add the mixture to water, extract it three times with dichloromethane, collect the organic phase, then dry it and distill off the organic solvent under reduced pressure to obtain a crude product. (3) Separate and purify the crude product by silica gel column chromatography to obtain the asymmetric disulfide.

6. The preparation method of an asymmetric disulfide according to claim 5, characterized in that, In step (1), the structural formula of the thiophenol raw material is: wherein, R is an electron-donating group or an electron-withdrawing group.

7. The preparation method of an asymmetric disulfide according to claim 6, characterized in that, The electron-donating group is Me, MeO or t-Bu; the electron-withdrawing group is F, Cl or Br.

8. The preparation method of an asymmetric disulfide according to claim 6, wherein, The substitution pattern of R is mono-substitution, di-substitution and tri-substitution.

9. According to the preparation method of an asymmetric disulfide as claimed in claim 8, the position of the mono-substitution is ortho, meta and para; the positions of the di-substitution are 2,4-substitution, 2,5-substitution, 2,6-substitution, 3,4-substitution and 3,5-substitution; the position of the tri-substitution is 2,4,5-substitution.

10. The preparation method of an asymmetric disulfide according to claim 5, characterized in that, In step (1), the organic solvent is dimethyl sulfoxide, N,N-dimethylformamide, ethanol, 1,4-dioxane or ethyl acetate; the conditions for the stirring reaction are room temperature and light, the reaction concentration is 0.1-2.0 M, the reaction time is 27-36 h; the light source for the light is purple LED, blue LED, green LED, white LED or ambient light.

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