Preparation method of disulfide

Abstract

The invention provides a preparation method of disulfide, and belongs to the field of organic synthesis. The preparation method of the disulfide provided by the invention comprises the following step: in the presence of copper acetate, pyridine and a solvent, reacting aryl mercaptan to obtain the disulfide. According to the method, the disulfide can be prepared in a pure organic solvent system at a relatively high yield.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and more specifically to a method for preparing disulfides. Background Technology

[0002] Disulfide compounds have many industrial applications. For example, Chinese patent CN 114502158 A discloses that dimethyl 6,6'-dithioalkyldipyridinecarboxylate can be used as a synthetic intermediate for IRAK degradation agents.

[0003] While there are various methods for synthesizing disulfide compounds in the existing technology, they all have certain limitations.

[0004] Chinese patent CN 114502158 A discloses the preparation of 6,6'-dithionedidyldipyridinecarboxylate dimethyl ester using iodine as an initiator and 6-thioalkylpyridine-2-carboxylate as a raw material; however, the yield of this reaction is only 24%.

[0005] The paper "Simple and efficient oxidative transformation of thiols to disulfides using Cu(NO3)2·3H2O in H2O / AcOEt" (Monatsh Chem (2014) 145: 1151–1154) discloses another method for preparing disulfides, which uses nitrates as catalysts and ethyl acetate and water as solvents, and can produce disulfides in extremely high yields. However, due to the poor solubility of nitrates in organic solvents, some poorly water-soluble organic compounds cannot be prepared using this method. Summary of the Invention

[0006] This invention was made to solve the above-mentioned problems, and its purpose is to provide a method for preparing disulfides that is applicable to a wider range of organic substrates and can guarantee a high yield.

[0007] This invention provides a method for preparing disulfides, characterized by the following reaction formula:

[0008]

[0009] In the above formula, X is C or N, and R is a C1-C5 alkyl group.

[0010] Includes the following steps:

[0011] In the presence of copper acetate, pyridine, and a solvent, compound 1 reacts to give compound 2.

[0012] The method for preparing disulfides provided by this invention may also have the following characteristics: wherein X is N and R is methyl.

[0013] The method for preparing disulfides provided by the present invention may also have the following feature: wherein the solvent is selected from any one or more of 1,2-dichloroethane, tetrahydrofuran, toluene, 2-methyltetrahydrofuran, or acetone.

[0014] The method for preparing disulfides provided by the present invention may also have the following feature: wherein the molar ratio of copper acetate to compound 1 is (0.2-1):1.

[0015] The method for preparing disulfides provided by the present invention may also have the following feature: wherein the molar ratio of pyridine to compound 1 is (0.8-1.2):1.

[0016] The method for preparing disulfides provided by the present invention may also have the following feature: wherein the mass-volume ratio of compound 1 to solvent is 1g:(15-30)mL.

[0017] The method for preparing disulfides provided by this invention may also have the following characteristic: the reaction temperature is 60-100℃.

[0018] The method for preparing disulfides provided by this invention may also include the following steps:

[0019] Compound 1, copper acetate, and pyridine were added to a solvent, heated to 60-100℃, and reacted for 0.5-8 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered, and the filtrate was washed with citric acid solution, dried, and subjected to column chromatography to obtain compound 2.

[0020] The method for preparing disulfides provided by this invention may also have the following feature: wherein the citric acid solution is a 5-15 wt% aqueous solution of citric acid.

[0021] The role and effect of invention

[0022] According to the method for preparing disulfides of the present invention, because copper acetate is used as a catalyst and pyridine is added, the present invention can obtain disulfides in a high yield in a pure organic solvent system. Detailed Implementation

[0023] To make the technical means, creative features, objectives and effects of this invention easy to understand, the invention will be specifically described below in conjunction with embodiments.

[0024] In the following embodiments, unless otherwise stated, all chemical reagents used in each embodiment are commercially available products.

[0025] <Example 1>

[0026] A method for preparing disulfides

[0027] This embodiment provides a method for preparing disulfides, with the following reaction formula:

[0028]

[0029] Includes the following steps:

[0030] 10 g of compound 1a (59.1 mmol, 1.0 eq), 11.8 g of copper acetate (59.1 mmol, 1.0 eq), and 4.7 g of pyridine (59.1 mmol, 1.0 eq) were added to 200 mL of 1,2-dichloroethane. The mixture was heated to 80 °C and stirred for 30 min. After cooling to room temperature, the mixture was filtered. The filtrate was washed with 10 wt% citric acid aqueous solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and subjected to column chromatography to give 7.8 g of compound 2a, with a yield of 78.5%.

[0031] <Example 2>

[0032] Based on Example 1, this embodiment has screened some reaction conditions. The screening results are shown in Table 1. Except for the conditions listed in Table 1, the other reaction conditions are the same as those in Example 1.

[0033] Table 1 Screening of reaction conditions

[0034]

[0035]

[0036] As shown in the table above, even catalytic amounts of copper acetate (0.2–0.5 eq) catalyze the reaction well. However, surprisingly, if pyridine is replaced with 2,2-bipyridine, the reaction fails to proceed. Even more surprisingly, without the addition of copper acetate, the desired product is obtained in a yield of approximately 10%. The role and effect of the embodiments

[0037] According to the disulfide preparation method described in the above embodiments, because copper acetate is used as a catalyst and pyridine is added, the present invention can obtain disulfides in a yield of more than 75% in a 1,2-dichloroethane solvent system.

[0038] Furthermore, this application unexpectedly discovered that even a catalytic amount of copper acetate (0.2-0.5) eq could effectively catalyze the reaction and achieve a satisfactory yield of 66-72%.

[0039] The above embodiments are preferred embodiments of the present invention and are not intended to limit the scope of protection of the present invention.

Claims

1. A method for preparing a disulfide, characterized in that, The reaction formula is as follows: In the above formula, X is C or N, and R is a C1-C5 alkyl group. Includes the following steps: In the presence of copper acetate, pyridine, and a solvent, compound 1 reacts to give compound 2.

2. The method for preparing disulfides according to claim 1, characterized in that: in, X is N, and R is methyl.

3. The method for preparing disulfides according to claim 1, characterized in that: in, The solvent is selected from any one or more of 1,2-dichloroethane, tetrahydrofuran, toluene, 2-methyltetrahydrofuran, or acetone.

4. The method for preparing disulfides according to claim 1, characterized in that: in, The molar ratio of copper acetate to compound 1 is (0.2-1):

1.

5. The method for preparing disulfides according to claim 1, characterized in that: in, The molar ratio of pyridine to compound 1 is (0.8-1.2):

1.

6. The method for preparing disulfides according to claim 1, characterized in that, in, The mass-to-volume ratio of compound 1 to the solvent is 1 g: (15-30) mL.

7. The method for preparing disulfides according to claim 1, characterized in that, in, The reaction temperature is 60-100℃.

8. The method for preparing disulfides according to claim 1, characterized in that, Includes the following steps: Compound 1, copper acetate, and pyridine were added to a solvent, heated to 60-100℃, and reacted for 0.5-8 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered, and the filtrate was washed with citric acid solution, dried, and subjected to column chromatography to obtain compound 2.

9. The method for preparing disulfides according to claim 8, characterized in that, in, The citric acid solution is a 5-15 wt% aqueous solution of citric acid.

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