阅读说明：本技术 一种对称的含二硫键化合物的制备方法 (Preparation method of symmetrical disulfide bond-containing compound ) 是由 鹿永娜 李晓曼 程夏民 范佳丽 闫辉 单士权 于 2021-08-24 设计创作，主要内容包括：本发明公开了一种对称的含二硫键化合物的制备方法,该方法包括以下步骤：将原料与氧化剂加入到含有溶剂的反应瓶中,在23W～85W节能灯照射下反应12～24h,将反应产物提纯后得到对称的含二硫键化合物；其中,所述原料为硫醇或者硫酚；所述氧化剂为三氯溴甲烷,所述溶剂为四氢呋喃。本发明方法操作简单,产率高(70～90％),适用性广,原料廉价易得,为对称的含有二硫键化合物的合成和生产提供了一条更好的途径。(The invention discloses a preparation method of a symmetrical compound containing a disulfide bond, which comprises the following steps: adding raw materials and an oxidant into a reaction bottle containing a solvent, reacting for 12-24 hours under the irradiation of a 23-85W energy-saving lamp, and purifying a reaction product to obtain a symmetrical compound containing a disulfide bond; wherein the raw material is mercaptan or thiophenol; the oxidant is trichlorobromomethane, and the solvent is tetrahydrofuran. The method disclosed by the invention is simple to operate, high in yield (70-90%), wide in applicability and cheap and easily available in raw materials, and provides a better way for synthesis and production of symmetrical compounds containing disulfide bonds.)

1. A method for preparing a symmetric disulfide bond-containing compound, comprising the steps of: adding raw materials and an oxidant into a reaction bottle containing a solvent, reacting for 12-24 hours under the irradiation of a 23-85W energy-saving lamp, and purifying a reaction product to obtain a symmetrical compound containing a disulfide bond; wherein the raw material is mercaptan or thiophenol; the oxidant is trichlorobromomethane, and the solvent is tetrahydrofuran.

2. The method for preparing a symmetric disulfide bond-containing compound according to claim 1, wherein the molar volume ratio of the starting material, the oxidizing agent and the solvent is 0.4 mmol: 0.4-2.0 mmol: 1-10 mL.

3. The method of claim 1, wherein the purification is specifically: and concentrating the reaction product to remove the organic solvent, and separating and enriching the concentrated product by using a silica gel column chromatography to obtain a symmetrical compound containing the disulfide bond.

4. The method for preparing a symmetric disulfide bond-containing compound according to claim 1, wherein said thiol is any one of n-octyl thiol, p-methoxybenzyl thiol, p-cyanobenzyl thiol, o-bromobenzyl thiol, p-bromobenzyl thiol, and p-tert-butylbenzyl thiol;

the thiophenol is any one of o-hydroxyphenylthiophenol, p-hydroxyphenylthiophenol, o-methoxythiophenol, o-chlorophenylthiophenol, p-chlorophenylthiophenol, o-bromophenylthiol, m-bromophenylthiol, p-bromothiophenol, m-fluorophenylthiophenol, p-fluorophenylthiophenol, m-trifluoromethylthiophenol and o-carboxythiophenol.

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of a symmetrical disulfide bond-containing compound.

Background

Disulfide bonds, also known as S-S bonds, can be formed by oxidation of two-SH groups. Organic disulfides are a common moiety in organic compounds and are important in chemistry and biology. Disulfides have applications ranging from antioxidants, pharmaceuticals, pesticides to rubber vulcanization agents. Disulfides are also the basis for the production of many fine chemicals and pharmaceuticals, as well as for the production of vulcanization agents for vulcanized rubber on an industrial scale. In biological systems, disulfide bond formation is crucial for folding of many polypeptides and proteins, and has some influence on the formation of the three-dimensional structure of the protein molecule. Based on the symmetry of the product, the products are mainly classified into symmetric disulfide bond-containing compounds and asymmetric disulfide bond-containing compounds. At present, there are many methods for preparing symmetric disulfide bond-containing compounds, and specific synthetic methods are listed as follows:

(1) the disulfide compound is synthesized by using sulfonyl chloride in an aqueous medium at room temperature, and the reaction equation is as follows:

during the reaction, the mercaptan reacts with phenylsulfonyl chloride under alkali treatment to form a thiosulfonate intermediate, and reacts with another mercaptan molecule to form a disulfide compound. Aryl thiols with different functionalities also react well in yields of around 90% (see literature 1: H.Xiao, J.Chen, M.Liu, H.Wu and J.Ding, Phosphorus, Sulfur Silicon Relat. Elem.,2009,184,2553.).

(2) Using Fe (BTC: 1,3, 5-benzoate) as a suitable, reusable catalyst, O₂Oxidizing mercaptan or thiophenol by using an oxidizing agent, and performing coupling reaction to form a symmetrical disulfide bond-containing compound with the yield of 60-90% (see the document 2: A. Dhakshinamoorthy, M. Alvaro and H. Garcia, chem. Commun.,2010,46, 6476), wherein the reaction equation is as follows:

(3) maleic anhydride is used as a promoting medium, urea-hydrogen peroxide is used as an oxidizing agent, mercaptan or thiophenol is oxidized, a coupling reaction is carried out to form a symmetrical compound containing a disulfide bond, the yield is 65-95% (see the document 3: F. Hosseinpoor and H. Golchoubian, Catal. Lett.,2006,111,165.), and the reaction equation is as follows:

(4) using HNO₃Oxidizing mercaptan or thiophenol by using an oxidant, and performing a coupling reaction to form a symmetrical disulfide bond-containing compound with a yield of 67-90% (reference 4: A.K.Misra and G.Agnihotri, Synth.Commun.,2004,34,1079.), wherein the reaction equation is as follows:

the preparation of symmetrical disulfide-containing compounds by the above methods has various problems, for example, the raw materials or catalysts used are somewhat complicated, Fe (BTC: 1,3, 5-benzoate) is expensive and not easily available, HNO₃The operation of the acid is dangerous as a strong acid with strong oxidizing property, and the acid has great harm to human bodies and the environment.

Disclosure of Invention

The invention aims to provide a preparation method of a symmetrical compound containing a disulfide bond, and aims to overcome the defects of the prior art in the background technology.

The invention is realized by a method for preparing a symmetrical disulfide bond-containing compound, which comprises the following steps: adding raw materials and an oxidant into a reaction bottle containing a solvent, reacting for 12-24 hours under the irradiation of a 23-85W energy-saving lamp, and purifying a reaction product to obtain a symmetrical compound containing a disulfide bond; wherein the raw material is mercaptan or thiophenol; the oxidant is trichlorobromomethane, and the solvent is tetrahydrofuran.

Preferably, the molar volume ratio of the raw material, the oxidant and the solvent is 0.4 mmol: 0.4-2.0 mmol: 5-10 mL.

Preferably, the purification is specifically: and concentrating the reaction product to remove the organic solvent, and separating and enriching the concentrated product by using a silica gel column chromatography to obtain a symmetrical compound containing the disulfide bond.

Preferably, the thiol is any one of n-octyl thiol, p-methoxybenzyl thiol, p-cyanobenzyl thiol, o-bromobenzyl thiol, p-bromobenzyl thiol and p-tert-butylbenzyl thiol;

the thiophenol is any one of o-hydroxyphenylthiophenol, p-hydroxyphenylthiophenol, o-methoxythiophenol, o-chlorophenylthiophenol, p-chlorophenylthiophenol, o-bromophenylthiol, m-bromophenylthiol, p-bromothiophenol, m-fluorophenylthiophenol, p-fluorophenylthiophenol, m-trifluoromethylthiophenol and o-carboxythiophenol.

In order to overcome the defects and shortcomings of the prior art, the invention provides a preparation method of a symmetrical disulfide bond-containing compound, in the preparation method, mercaptan or thiophenol is used as a raw material, under the irradiation condition of a 23W energy-saving lamp, an oxidant trichlorobromomethane is used for inducing generation of disulfide bonds, and the chemical reaction equation of the synthetic process is as follows:

on the basis, the reaction product is purified to obtain the symmetrical compound containing the disulfide bond.

Compared with the defects and shortcomings of the prior art, the invention has the following beneficial effects: the method disclosed by the invention is simple to operate, high in yield (70-90%), wide in applicability and cheap and easily available in raw materials, and provides a better way for synthesis and production of symmetrical compounds containing disulfide bonds.

Drawings

FIG. 1 is a NMR spectrum of the product of the coupling reaction of example 1;

FIG. 2 is a NMR spectrum of the product of the coupling reaction of example 2;

FIG. 3 is a NMR spectrum of the product of the coupling reaction of example 3;

FIG. 4 is a NMR spectrum of the product of the coupling reaction of example 4;

FIG. 5 is a NMR spectrum of the product of the coupling reaction of example 5;

FIG. 6 is a NMR spectrum of the product of the coupling reaction of example 6;

FIG. 7 is a NMR spectrum of the product of the coupling reaction of example 7;

FIG. 8 is a NMR spectrum of the product of the coupling reaction of example 8;

FIG. 9 is a NMR spectrum of the product of the coupling reaction of example 9;

FIG. 10 is a NMR spectrum of the product of the coupling reaction of example 10;

FIG. 11 is a NMR spectrum of the product of the coupling reaction of example 11;

FIG. 12 is a NMR spectrum of the product of the coupling reaction of example 12;

FIG. 13 is a NMR spectrum of the product of the coupling reaction of example 13;

FIG. 14 is a NMR spectrum of the product of the coupling reaction of example 14;

FIG. 15 is a NMR spectrum of the product of the coupling reaction of example 15;

FIG. 16 is a NMR spectrum of the product of the coupling reaction of example 16;

FIG. 17 is a NMR spectrum of the product of the coupling reaction of example 17;

FIG. 18 is a NMR spectrum of the product of the coupling reaction of example 18.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

Example 1

59.4mg (0.4mmol) of n-octyl mercaptan and 237.9mg (1.2mmol) of trichlorobromomethane are added into a 10mL Schlenk container, then 2mL of tetrahydrofuran is added by a syringe, the mixture reacts for 16h under the irradiation of a 23W energy-saving lamp at room temperature, after the reaction is completed, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to obtain colorless liquid: 53.2mg, yield: 90 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 1.

The characterization data for this product are:¹H NMR(401MHz,CDCl₃)δ2.67(t,J＝7.28Hz,4H),1.70–1.63(m,4H),1.39–1.34(m,4H),1.31–1.27(m,16H),0.88(t,J＝6.76Hz,6H)。

example 2

50.4mg (0.4mmol) of o-hydroxyphenethiol and 237.9mg (1.2mmol) of trichlorobromomethane are added into a 10mL Schlenk container, then 2mL of tetrahydrofuran is added by a syringe, the mixture reacts for 10h under the irradiation of a 23W energy-saving lamp at room temperature, after the reaction is completed, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to obtain colorless liquid: 45.1mg, yield: 91 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 2.

The characterization data for this product are:¹H NMR(401MHz,Chloroform-d)δ7.35(td,J＝7.8,1.6Hz,2H),7.23(dd,J＝7.7,1.7Hz,2H),7.00(dd,J＝8.2,1.2Hz,2H),6.83(td,J＝7.6,1.3Hz,2H),6.26(s,2H)。

example 3

50.4mg (0.4mmol) of p-hydroxyphenylthiophenol and 237.9mg (1.2mmol) of trichlorobromomethane are added into a 10mL Schlenk vessel, then 2mL of tetrahydrofuran is added by a syringe, the reaction is carried out for 10h at room temperature under the irradiation of a 23W energy-saving lamp, after the reaction is completed, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to obtain a yellow solid: 47.5mg, yield: 85 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 3.

The characterization data for this product are:¹H NMR(401MHz,CDCl₃)δ7.05(d,J＝8.3Hz,4H),6.55(d,J＝8.4Hz,4H)。

example 4

56.1mg (0.4mmol) of o-methoxythiophenol and 237.9mg (1.2mmol) of trichlorobromomethane are introduced into a 10mL Schlenk vessel, 2mL of tetrahydrofuran are then introduced by means of a syringe, the reaction is carried out at room temperature for 12h under the irradiation of a 23W energy-saving lamp, after completion of the reaction, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to give a white solid: 50.8mg, yield: 91 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 4.

The characterization data for this product are:¹H NMR(401MHz,CDCl₃)δ7.53(dd,J＝7.8,1.5Hz,2H),7.19(dt,J＝7.6,1.3Hz,2H),6.91(t,J＝7.9Hz,2H),6.86(d,J＝8.1Hz,2H),3.90(s,6H)。

example 5

57.8mg (0.4mmol) of o-chlorothiophenol and 237.9mg (1.2mmol) of trichlorobromomethane are added into a 10mL Schlenk vessel, then 2mL of tetrahydrofuran is added by a syringe, the reaction is carried out for 12h at room temperature under the irradiation of a 23W energy-saving lamp, after the reaction is completed, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to obtain a white solid: 51mg, yield: 91 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 5.

The characterization data for this product are:¹H NMR(401MHz,DMSO-d₆)δ7.58(d,J＝7.9Hz,2H),7.55(d,J＝7.8Hz,2H),7.40(t,J＝7.6Hz,2H),7.33(t,J＝7.6Hz,2H)。

example 6

57.6mg (0.4mmol) of p-chlorothiophenol and 237.9mg (1.2mmol) of trichlorobromomethane are added into a 10mL Schlenk vessel, then 2mL of tetrahydrofuran is added by a syringe, the reaction is carried out for 12h at room temperature under the irradiation of a 23W energy-saving lamp, after the reaction is completed, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to obtain a white solid: 52.9mg, yield: 92.1 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 6.

The characterization data for this product are:¹H NMR(401MHz,DMSO-d₆)δ7.53(d,J＝8.8Hz,4H),7.45(d,J＝8.7Hz,4H)。

example 7

75.6mg (0.4mmol) of o-bromophenylthiol and 237.9mg (1.2mmol) of trichlorobromomethane are added into a 10mL Schlenk container, then 2mL of tetrahydrofuran is added by a syringe, the mixture reacts for 13h under the irradiation of a 23W energy-saving lamp at room temperature, after the reaction is completed, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to obtain a white solid: 71.8mg, yield: 96 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 7.

The characterization data for this product are:¹H NMR(401MHz,DMSO-d₆)δ7.65(d,J＝7.6Hz,2H),7.50(d,J＝7.9Hz,2H),7.38(t,J＝7.5Hz,2H),7.20(t,J＝7.3Hz,2H)。

example 8

75.8mg (0.4mmol) of m-bromophenylthiol and 237.9mg (1.2mmol) of trichlorobromomethane are added into a 10mL Schlenk container, then 2mL of tetrahydrofuran is added by a syringe, the mixture reacts for 12h under the irradiation of a 23W energy-saving lamp at room temperature, after the reaction is completed, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to obtain colorless liquid: 64.3mg, yield: 86 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 8.

The characterization data for this product are:¹H NMR(401MHz,DMSO-d₆)δ7.68(s,2H),7.52–7.47(m,4H),7.36–7.31(m,2H)。

example 9

75.6mg (0.4mmol) of p-bromothiophenol and 237.9mg (1.2mmol) of trichlorobromomethane are added into a 10mL Schlenk vessel, then 2mL of tetrahydrofuran is added by a syringe, the reaction is carried out for 12h at room temperature under the irradiation of a 23W energy-saving lamp, after the reaction is completed, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to obtain colorless liquid: 63.8mg, yield: 85 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 9.

The characterization data for this product are:¹H NMR(401MHz,DMSO-d₆)7.58(d,J＝8.7Hz,1H),7.45(d,J＝8.8Hz,1H)。

example 10

51.1mg (0.4mmol) of m-fluorobenzothiophenol and 237.9mg (1.2mmol) of trichlorobromomethane are added into a 10mL Schlenk container, then 2mL of tetrahydrofuran is added by a syringe, the mixture reacts for 12h under the irradiation of a 23W energy-saving lamp at room temperature, after the reaction is completed, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to obtain colorless liquid: 47.7mg, yield: 94 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 10.

The characterization data for this product are:¹H NMR(401MHz,DMSO-d₆)δ7.44–7.37(m,2H),7.34–7.32(m,4H),7.11–7.07(m,2H)。

example 11

51.2mg (0.4mmol) of p-fluorobenzothiophenol and 237.9mg (1.2mmol) of trichlorobromomethane are added into a 10mL Schlenk container, then 2mL of tetrahydrofuran is added by a syringe, the reaction is carried out for 12h at room temperature under the irradiation of a 23W energy-saving lamp, after the reaction is completed, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to obtain colorless liquid: 42.8mg, yield: 84 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 11.

The characterization data for this product are:¹H NMR(401MHz,CDCl₃)δ7.44(dd,J＝9.0,5.1Hz,4H),7.01(dd,J＝8.9,8.5Hz,4H)。

example 12

Adding 71.2mg (0.4mmol) of m-trifluorothiophenol and 0.4mmol of trichlorobromomethane into a 10mL Schlenk container, adding 1mL of tetrahydrofuran by using a syringe, reacting for 12h at room temperature under the irradiation of an 85W energy-saving lamp, concentrating to remove the solvent after the reaction is completed, and separating the crude product by silica gel column chromatography (eluent: petroleum ether) to obtain a white solid: 53.5mg, yield: 76 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 12.

The characterization data for this product are:¹H NMR(401MHz,CDCl₃)δ7.75(s,2H),7.66(d,J＝7.8Hz,2H),7.51(d,J＝7.8Hz,2H),7.45(t,J＝7.8Hz,2H)。

example 13

61.6mg (0.4mmol) of o-carboxythiophenol and 237.9mg (1.2mmol) of trichlorobromomethane are added into a 10mL Schlenk vessel, 10mL of tetrahydrofuran is added by a syringe, the reaction is carried out for 24h at room temperature under the irradiation of a 50W energy-saving lamp, after the reaction is completed, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to obtain a white solid: 57.0mg, yield: 93 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 13.

The characterization data for this product are:¹H NMR(401MHz,DMSO-d₆)δ8.02(d,J＝7.6Hz,2H),7.62(d,J＝8.0Hz,2H),7.53(t,J＝7.5Hz,2H),7.32(t,J＝7.2Hz,2H)。

example 14

61.5mg (0.4mmol) of p-methoxybenzyl mercaptan and 2.0mmol of trichlorobromomethane are added into a 10mL Schlenk container, then 2mL of tetrahydrofuran is added by a syringe, the reaction is carried out for 12h at room temperature under the irradiation of a 23W energy-saving lamp, after the reaction is completed, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to obtain a white solid: 56.9mg, yield: 93 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 14.

The characterization data for this product are:¹H NMR(401MHz,CDCl₃)δ7.17(d,J＝7.52Hz,4H),6.86(d,J＝7.44Hz,4H),3.80(s,6H),3.59(s,4H)。

example 15

59.6mg (0.4mmol) of p-cyanobenzyl mercaptan and 237.9mg (1.2mmol) of trichlorobromomethane are added into a 10mL Schlenk vessel, then 2mL of tetrahydrofuran is added by a syringe, the reaction is carried out for 12h at room temperature under the irradiation of a 23W energy-saving lamp, after the reaction is completed, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to obtain a white solid: 56.9mg, yield: 96 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 15.

The characterization data for this product are:¹H NMR(401MHz,CDCl₃)δ7.62(d,J＝8.20Hz,4H),7.32(d,J＝8.20Hz,4H),3.62(s,4H)。

example 16

81.2mg (0.4mmol) of o-bromobenzyl mercaptan and 237.9mg (1.2mmol) of trichlorobromomethane are added into a 10mL Schlenk vessel, then 2mL of tetrahydrofuran is added by a syringe, the reaction is carried out for 12h at room temperature under the irradiation of a 23W energy-saving lamp, after the reaction is completed, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to obtain a white solid: 64.2mg, yield: 80 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 16.

The characterization data for this product are:¹H NMR(401MHz,DMSO-d₆)δ7.62(d,J＝8.00Hz,2H),7.37(d,J＝4.16Hz,4H),7.27–7.22(m,2H),3.89(s,4H)。

example 17

81.1mg (0.4mmol) of p-bromobenzyl mercaptan and 237.9mg (1.2mmol) of trichlorobromomethane are introduced into a 10mL Schlenk vessel, then 2mL of tetrahydrofuran are introduced by a syringe, the reaction is carried out at room temperature for 12h under the irradiation of a 23W energy-saving lamp, after the reaction is completed, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to obtain a white solid: 64.7mg, yield: 81 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 17.

The characterization data for this product are:¹H NMR(401MHz,DMSO-d₆)δ7.53(d,J＝8.20Hz,4H),7.23(d,J＝8.12Hz,4H),3.76(s,4H)。

example 18

72.1mg (0.4mmol) of p-tert-butyl benzyl mercaptan and 237.9mg (1.2mmol) of trichlorobromomethane are added into a 10mL Schlenk vessel, then 2mL of tetrahydrofuran is added by a syringe, the reaction is carried out for 12h at room temperature under the irradiation of a 23W energy-saving lamp, after the reaction is completed, the solvent is removed by concentration, and the crude product is separated by silica gel column chromatography (eluent: petroleum ether) to obtain a white solid: 60.3mg, yield: 84 percent. The nuclear magnetic spectrum analysis of the reaction product is shown in FIG. 18.

The characterization data for this product are:¹H NMR(401MHz,CDCl₃)δ7.36(d,J＝8.04Hz,4H),7.18(d,J＝8.04Hz,4H),3.60(s,4H),1.32(s,18H)。

the above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.