A method for the preparation of a thiosulfonate in an aqueous phase based on a sulfinic acid

Abstract

The application provides a preparation method of sulfonic acid ester in a sulfonic acid water phase, and belongs to the technical field of organic synthesis. The specific preparation method is as follows: aromatic sulfonic acid is added into water without catalyst and redox reagent, and sulfonic acid ester can be obtained by reacting for 2 hours at a temperature of 100 DEG C or above. The method has the advantages of simple raw material, high yield, mild reaction condition, easy control, less waste, and good social value and industrialization prospect.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of organic synthesis, and particularly relates to a preparation method of thiosulfonate in water phase based on sulfinic acid. BACKGROUND

[0002] Thiosulfonate compounds are an important class of sulfur-containing organic compounds, which have shown wide application prospects in many fields such as organic synthesis, polymers, medicines, pesticides and the like, and have unique biological and chemical activities. Therefore, thiosulfonate compounds have been concerned and developed in the field of organic synthesis chemistry research.

[0003] So far, the known synthesis methods of thiosulfonate compounds mainly include the following methods (such as Figure 1 ):However, most of these methods need additional equivalent oxidizing and reducing reagents, or use relatively expensive or odorant reagents. At the same time, these reactions are generally carried out in organic solvents such as acetonitrile, N,N-dimethylformamide and the like, which are not green synthesis in the synthesis. Therefore, it is very valuable to develop a green synthesis of thiosulfonate which can be applied in industry. SUMMARY

[0004] To solve the above technical problems, the present application provides a preparation method of thiosulfonate in water phase based on sulfinic acid. The present application uses water as a solvent and a promoter, and uses aromatic sulfinic acid as a starting material to synthesize the target product thiosulfonate. The present application uses aromatic sulfinic acid as a sulfur source, and various substituents can be connected to the benzene ring in the aromatic sulfinic acid. Without additional catalysts or redox reagents, the construction of the target product thiosulfonate can be realized in water by heating. The reaction conditions of the method of the present application are simple and mild, the operation is convenient, and the method has wide adaptability and is very suitable for large-scale production in industry.

[0005] To achieve the above purpose, the present application provides a preparation method of thiosulfonate in water phase based on sulfinic acid, which comprises the following steps: under the condition of no catalyst and no redox reagent, aromatic sulfinic acid is added to water, and reaction is carried out at a temperature of 100 DEG C or higher, so that thiosulfonate can be obtained.

[0006] Further, the structural formula of thiosulfonate is as follows:

[0007]

[0008] R is a substituted or unsubstituted C1-C3 alkyl, a halogen group, a nitro group, a methoxy group or a phenyl group, and is preferably a methyl group, a chlorine group, a bromine group, an iodine group, a fluorine group, a nitro group, a methoxy group, a trifluoromethyl group or a phenyl group.

[0009] ​Further, the present application uses aromatic sulfinic acid as raw material to synthesize thiosulfonate in water, and the reaction route is as follows:

[0010]

[0011] R is substituted or unsubstituted C1-C3 alkyl, halogen group, nitro group, methoxy group or phenyl group, preferably methyl, chlorine, bromine, iodine, fluorine, nitro group, methoxy group, trifluoromethyl or phenyl.

[0012] In the present application, the substitution on the benzene ring of aromatic sulfinic acid can be ortho, meta or para.

[0013] Further, the reaction temperature is 100-150 DEG C.

[0014] Further, the reaction temperature is 120 DEG C.

[0015] Further, the reaction time is 2 hours.

[0016] Further, the structural formula of the aromatic sulfinic acid is as follows:

[0017]

[0018] R is substituted or unsubstituted C1-C3 alkyl, halogen group, nitro group, methoxy group or phenyl group.

[0019] Further, R in the aromatic sulfinic acid is methyl, chlorine, bromine, iodine, fluorine, nitro group, methoxy group, trifluoromethyl or phenyl.

[0020] Further, the aromatic sulfinic acid is p-toluenesulfinic acid, p-chlorobenzenesulfinic acid, benzenesulfinic acid, o-chlorobenzenesulfinic acid, naphthalenesulfinic acid, p-trifluoromethylbenzenesulfinic acid, p-bromobenzenesulfinic acid sodium or p-methoxybenzenesulfinic acid.

[0021] The reaction mechanism of the present application is as follows (taking p-chlorobenzenesulfinic acid as an example):

[0022]

[0023] Compared with the prior art, the present application has the following advantages and technical effects:

[0024] The present application provides a method for preparing thiosulfonate compound with green efficiency and low cost, which does not need to add catalyst and redox reagent, and uses cheap and easily available, green and pollution-free water as reaction solvent to prepare thiosulfonate compound with high yield under mild conditions. BRIEF DESCRIPTION OF DRAWINGS

[0025] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an undue limitation of the invention. In the drawings:

[0026] Figure 1 This refers to the existing methods for synthesizing thiosulfonates;

[0027] Figure 2 The product obtained in Example 1 of this invention 1 HNMR;

[0028] Figure 3 The product obtained in Example 1 of this invention 13 CNMR;

[0029] Figure 4 The product obtained in Example 2 of this invention 1 HNMR;

[0030] Figure 5 The product obtained in Example 2 of this invention 13 CNMR. Detailed Implementation

[0031] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0032] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0033] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0034] Many modifications and variations of the described implementations of the present application can be made without departing from its spirit or scope, as will be apparent to those skilled in the art. Other implementations of the present application will be apparent to those skilled in the art from the foregoing description. The scope of the present application is to be limited only by the claims.

[0035] As used herein, the terms "comprises", "comprising", "includes", "including", "has", "having", "contains", "containing", or variations thereof, are intended to be open-ended terms that mean inclusion, but not limited to, the listed material or step.

[0036] The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and raw materials described are all commercially available or prepared according to known methods unless otherwise specified.

[0037] In the embodiments of the present application, the type of water is not limited, and pure water, distilled water or deionized water can be used.

[0038] Example 1

[0039] 10 mmol (1.56 g) of p-toluenesulfinic acid was weighed, 20 mL of distilled water was added, and the reaction was carried out at 120°C for 2 hours. After the reaction was completed, water and ethyl acetate were added for extraction, the water layer was separated, the organic phase was combined, and anhydrous sodium sulfate was added for drying, followed by column chromatography separation. The collected components were analyzed by thin layer chromatography to determine that they were all target products. The components containing the products were combined, concentrated to dryness by rotary evaporation, weighed, and the yield was calculated. The yield was 88%, and the purity was 99%. The obtained product (S-p-tolyl-4-methylbenzenesulfinate, SRN number 8680081) had the following spectral data: 1 HNMR see Figure 2 , 13 CNMR see Figure 3 , the nuclear magnetic data are as follows:1H NMR (400 MHz, Chloroform-d) δ 7.52-7.42 (m, 2H), 7.30-7.19 (m, 4H), 7.16 (d, J = 7.9 Hz, 2H), 2.44 (s, 3H), 2.39 (s, 3H).13C NMR (101 MHz, Chloroform-d) δ 144.72, 142.17, 140.57, 136.62, 130.33, 129.49, 127.72, 124.70, 21.78, 21.60.

[0040] Example 2

[0041] Take 10 mmol (1.75 g) of p-chlorobenzenesulfinic acid, add 20 mL of distilled water, and react at 120°C for 2 hours. After the reaction is complete, add water and ethyl acetate to extract, separate the water layer, combine the organic phase, dry it over anhydrous sodium sulfate, and then perform column chromatography separation. The collected components are analyzed by thin layer chromatography to determine that they are all target products. The components containing the products are combined, concentrated to dryness by rotary evaporation, weighed, and the yield is calculated. The yield is 69%, and the purity is 98%. The obtained product (S-4-chlorophenyl-4-chlorophenyl sulfide, SRN number 157982) has the following nuclear magnetic data: 1 HNMR see Figure 4 , 13 CNMR see Figure 5 , and the nuclear magnetic data are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.60-7.47 (m, 2H), 7.45-7.39 (m, 2H), 7.38-7.33 (m, 2H), 7.33-7.28 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 141.42, 140.69, 138.69, 137.82, 130.05, 129.41, 129.06, 126.14.

[0042] Example 3

[0043] Take 10 mmol (1.42 g) of benzenesulfinic acid, add 20 mL of distilled water, and react at 120°C for 2 hours. After the reaction is complete, add water and ethyl acetate to extract, separate the water layer, combine the organic phase, dry it over anhydrous sodium sulfate, and then perform column chromatography separation. The collected components are analyzed by thin layer chromatography to determine that they are all target products. The components containing the products are combined, concentrated to dryness by rotary evaporation, weighed, and the yield is calculated. The yield is 83%, and the nuclear magnetic data of the obtained product are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.56 (dd, J = 8.4, 2.9 Hz, 3H), 7.53-7.28 (m, 7H). 13 C NMR (101 MHz, Chloroform-d) δ 143.00, 136.70, 133.77, 131.55, 129.56, 128.92, 127.91, 127.65.

[0044] Example 4

[0045] Take 10 mmol (1.75 g) of o-chlorobenzenesulfinic acid, add 20 mL of distilled water, and react at 120°C for 2 hours. After the reaction is complete, add water and ethyl acetate to extract, separate the water layer, combine the organic phase, dry with anhydrous sodium sulfate, and then perform column chromatography separation. The collected components are analyzed by thin layer chromatography to determine that they are all target products. The components containing the products are combined, concentrated to dryness by rotary evaporation, weighed, and the yield is calculated. The yield is 69%, and the nuclear magnetic resonance data of the product obtained is as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.57 (dd, J = 7.8, 1.6 Hz, 1H), 7.53-7.41 (m, 3H), 7.35-7.25 (m, 2H), 7.25-7.12 (m, 2H). 13 CNMR (101 MHz, Chloroform-d) δ 140.51, 140.10, 134.87, 133.25, 133.13, 132.59, 131.17, 130.40, 127.81, 126.89, 126.74.

[0046] Example 5

[0047] Take 10 mmol (1.75 g) of o-chlorobenzenesulfinic acid, add 20 mL of distilled water, and react at 120°C for 2 hours. After the reaction is complete, add water and ethyl acetate to extract, separate the water layer, combine the organic phase, dry with anhydrous sodium sulfate, and then perform column chromatography separation. The collected components are analyzed by thin layer chromatography to determine that they are all target products. The components containing the products are combined, concentrated to dryness by rotary evaporation, weighed, and the yield is calculated. The yield is 69%, and the nuclear magnetic resonance data of the product obtained is as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.97 (d, J = 1.9 Hz, 1H), 7.91 (dd, J = 8.8, 3.3 Hz, 2H), 7.85 (dd, J = 5.1, 3.2 Hz, 2H), 7.75 (d, J = 8.5 Hz, 1H), 7.71-7.65 (m, 3H), 7.63-7.46 (m, 4H), 7.37 (dd, J = 8.6, 1.8 Hz, 1H). 13 CNMR (101 MHz, Chloroform-d) δ 139.67, 137.73, 135.14, 134.13, 133.28, 131.86, 131.62, 129.47, 129.44, 129.37, 129.35, 129.16, 128.42, 128.29, 127.92, 127.76, 127.72, 126.95, 125.18, 122.43.

[0048] Example 6

[0049] Weigh 10 mmol (2.10 g) of p-trifluoromethylbenzenesulfinic acid, add 20 mL of distilled water, and react at 120°C for 2 hours. After the reaction is complete, add water and ethyl acetate to extract, separate the aqueous layer, combine the organic phase, dry over anhydrous sodium sulfate, and then perform column chromatography to separate. The collected fractions are analyzed by thin layer chromatography to determine that they are all target products, the fractions containing the product are combined, concentrated to dryness by rotary evaporation, weighed, and the yield is calculated. The yield is 51%, and the nuclear magnetic resonance data of the obtained product are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.79-7.69 (m, 4H), 7.65 (d, J = 8.2 Hz, 2H), 7.54 (d, J = 8.1 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 146.20, 136.86, 135.82, 135.49, 133.92, 133.59, 131.71, 128.07, 126.71, 126.67, 126.64, 126.60, 126.51, 126.47, 126.44, 126.40, 124.82, 124.40, 122.11, 121.68.

[0050] Example 7

[0051] Weigh 10 mmol (2.19 g) of p-bromobenzenesulfinic acid, add 20 mL of distilled water, and react at 120°C for 2 hours. After the reaction is complete, add water and ethyl acetate to extract, separate the aqueous layer, combine the organic phase, dry over anhydrous sodium sulfate, and then perform column chromatography to separate. The collected fractions are analyzed by thin layer chromatography to determine that they are all target products, the fractions containing the product are combined, concentrated to dryness by rotary evaporation, weighed, and the yield is calculated. The yield is 54%, and the nuclear magnetic resonance data of the obtained product are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.69-7.57 (m, 2H), 7.55-7.48 (m, 2H), 7.48-7.40 (m, 2H), 7.29-7.20 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 141.88, 137.86, 132.95, 132.31, 129.22, 128.97, 127.05, 126.62.

[0052] Example 8

[0053] Take 10 mmol (1.72 g) of p-methoxybenzenesulfinic acid, add 20 mL of distilled water, and react at 120°C for 2 hours. After the reaction is complete, add water and ethyl acetate to extract, separate the aqueous layer, combine the organic phase, dry with anhydrous sodium sulfate, and then perform column chromatography separation. The collected components are analyzed by thin layer chromatography to determine that they are all target products. The components containing the products are combined, concentrated to dryness by rotary evaporation, weighed, and the yield is calculated. The yield is 69%. The nuclear magnetic resonance data of the obtained product are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.63-7.40 (m, 2H), 7.39-7.15 (m, 2H), 7.02-6.72 (m, 4H), 3.88 (s, 3H), 3.84 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 163.61, 162.28, 138.45, 134.90, 129.97, 118.93, 115.00, 113.92, 55.82, 55.57.

[0054] Example 9

[0055] Take 10 mmol (1.56 g) of p-toluenesulfinic acid, add 20 mL of distilled water, and react at 100°C for 2 hours. After the reaction is complete, add water and ethyl acetate to extract, separate the aqueous layer, combine the organic phase, dry with anhydrous sodium sulfate, and then perform column chromatography separation. The collected components are analyzed by thin layer chromatography to determine that they are all target products. The components containing the products are combined, concentrated to dryness by rotary evaporation, weighed, and the yield is calculated. The yield is 79%.

[0056] Example 10

[0057] Take 10 mmol (1.56 g) of p-toluenesulfinic acid, add 20 mL of distilled water, and react at 140°C for 2 hours. After the reaction is complete, add water and ethyl acetate to extract, separate the aqueous layer, combine the organic phase, dry with anhydrous sodium sulfate, and then perform column chromatography separation. The collected components are analyzed by thin layer chromatography to determine that they are all target products. The components containing the products are combined, concentrated to dryness by rotary evaporation, weighed, and the yield is calculated. The yield is 85%.

[0058] From Examples 1, 9-10, it can be seen that the yield of the product is the highest at a temperature of 120°C. If the temperature is higher, part of the diphenyl sulfide is generated, which reduces the yield of the product.

[0059] Comparative Example 1

[0060] Take 10 mmol (1.56 g) of p-toluenesulfinic acid, add 20 mL of distilled water, and react at 80°C for 2 hours. After the reaction is complete, add water and ethyl acetate to extract, separate the aqueous layer, combine the organic phase, and track the reaction by thin layer chromatography. Only the starting material is present, and no product is generated. The yield is 0%. At lower temperatures, the reaction cannot proceed.

[0061] The above merely describes the preferred embodiments of the present application, but the protection scope of the present application is not limited thereto. Any changes or substitutions within the technical scope disclosed by the present application can be easily conceived by those skilled in the art, and should be encompassed within the protection scope of the present application. Therefore, the protection scope of the present application should be subject to the protection scope of the claims.

Claims

1. A process for the preparation of a thiosulfinic ester in an aqueous phase based on a sulfinic acid, characterized in that, comprising the step of adding an aromatic sulfinic acid to water in the absence of a catalyst and an oxidation-reduction reagent and reacting at a temperature of 120°C for 2 hours to obtain a thiosulfonate; The sulfonic acid ester has a structural formula of , The aromatic sulfinic acid has a structural formula of , the aromatic sulfinic acid is selected from the group consisting of p-toluenesulfinic acid, p-chlorobenzenesulfinic acid, benzenesulfinic acid, o-chlorobenzenesulfinic acid, naphthalenesulfinic acid, p-trifluoromethylbenzenesulfinic acid, sodium p-bromobenzenesulfinic acid or p-methoxybenzenesulfinic acid.

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