Synthesis method of N-iodosuccinimide

Abstract

The invention relates to a green and economic synthesis method of N-iodosuccinimide, which comprises the following steps: dropwise adding a strong alkali solution into a succinimide saturated solution, keeping the pH value at 8-9, and obtaining a succinimide sodium salt reaction solution after 60 minutes; after iodination, inorganic iodide and N-iodosuccinimide are obtained, and filtrate can be reused. According to the process, a circulating mode is adopted, almost no three wastes are generated, the reaction condition is mild, the energy consumption is reduced, the requirement on reaction equipment is low, the safety of the process is improved, the reaction yield is high, the yield of succinimide salt is more than 99% after the process is applied, the yield of iodo is more than 95%, and the total yield is more than 94%.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for synthesizing N-iodosuccinimide. Background Art

[0002] N-iodosuccinimide, abbreviated as NIS, with CAS number 516-12-1, is a very important classic organic iodide reagent, most commonly used as an iodination reagent for the replacement of active α-hydrogen and aryl hydrogen. In recent years, with the expansion and deepening of research, NIS has not only found important applications in iodination reactions, but also has a wide range of applications in electrophilic cyclization, ring opening and expansion, protective agent removal, glycosidation, oxidation, polymerization, and other reactions. As the uses of NIS continue to be discovered, its synthesis and preparation methods have gradually become a research hotspot. How to achieve the green and efficient synthesis of NIS has become the main research content of this invention.

[0003] The chemical structural formula is:

[0004]

[0005] The mainstream synthesis processes of NIS reported so far are mainly the following:

[0006] The first method (Liu Zhendong et al., "Chemical Bulletin", Improvement of the Preparation Method of N-iodosuccinimide (NIS)) is to first use succinimide and silver oxide to prepare silver succinimide, and then iodinate the silver succinimide with refined iodine to obtain N-iodosuccinimide.

[0007] Ag+2HNO3(concentrated)=AgNO3+NO2+H2O

[0008] 2AgNO3+2NaOH=Ag2O+2NaNO3+H2O

[0009]

[0010] It is reported that the laboratory yield of this synthesis process is less than 85%, and concentrated nitric acid is used in the preparation of silver oxide, which produces nitrogen dioxide, polluting the environment and making post-processing difficult; the reflux reaction has high temperature and high energy consumption; the crystallization process of silver succinimide requires crystallization at room temperature overnight, which takes a long time; the use of precious metal silver is costly, and the by-product silver iodide is mainly used for artificial rainfall and has a small demand.

[0011] The second method is the use of chloro- or bromo-succinimide for iodination.

[0012]

[0013] The N-chlorosuccinimide process reportedly has a one-step yield of 89%, and the N-bromosuccinimide process has a one-step yield of 80%. However, both halogenated succinimides are inherently valuable and widely used. While the one-step yield of iodosuccinimide prepared from succinimide is high, the two-step yield is not significantly higher than the silver oxide process. Furthermore, both halogenation and iodination processes generate large amounts of waste salt and solid waste, requiring additional processing costs. Summary of the Invention

[0014] N-iodosuccinimide is an important organic iodide reagent that plays an irreplaceable role in many reactions. However, based on succinimide (succinimide) as the starting material, the two types of synthesis methods in the background art have unsatisfactory reaction yields and produce a lot of three wastes. In particular, the silver oxide process not only produces nitrogen oxides, but also the high price of metallic silver, making it unprofitable to use. In addition, the reaction conditions are also an important part to consider. The silver oxide process requires high-temperature reflux, which consumes a lot of energy.

[0015] The present invention aims to provide a green and economical method for synthesizing N-iodosuccinimide. The target product prepared by the method has high purity and yield, and the reaction efficiency is very high. Compared with the silver oxide method (which requires overnight crystallization at room temperature), the reaction time is shortened; the reaction conditions are mild, the energy consumption is low, the operation process is simple, the safety is high, and the production cost is lower; and high-value inorganic iodide is simultaneously produced as a by-product during the reaction process.

[0016] The specific technical contents of the present invention are as follows:

[0017]

[0018] A method for synthesizing N-iodosuccinimide as shown in the above formula comprises the following steps:

[0019] S1. Add succinimide finished product to 2.9-3.1 times the mass of water to prepare succinimide solution A;

[0020] S2. Solution B (a strong base solution at a molar ratio of 1-1.01) was added dropwise to solution A, and the pH was adjusted to 8-9. After stirring for 30 minutes, the pH was re-measured and remained unchanged to obtain reaction solution C;

[0021] S3. The reaction solution C was concentrated and filtered to obtain a solid D and a filtrate E. The solid D was dried and the filtrate was applied as a mother liquor to the next batch of reactions;

[0022] S4. Under light-shielding conditions, dissolve the iodine reagent G (0.95-1.02 times the molar amount of sodium succinimide) in an organic solvent F to obtain a solution G, and dissolve the solid D in an organic solvent F to obtain a solution H;

[0023] S5. Under light-proof conditions, at 0-10 ° C, solution H was added dropwise to solution G, stirring while adding dropwise for 30 min. After the addition, the reaction solution was stirred at 0-10 ° C for 2 h to obtain a reaction solution;

[0024] S6. Protect from light and filter the reaction solution I. The filter cake J is the inorganic iodide; the filtrate K is the product phase.

[0025] S7. Concentrate K in the dark until a large amount of solid precipitates, then cool and filter. Dry the filter cake L in a dark, vacuum-dry it to obtain the product NIS. Apply the filtrate M to the filtrate K.

[0026] See the process flow chart Figure 1 and Figure 2 .

[0027] The alkali in the strong alkali solution in S2 is selected from any one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium alkoxide, and potassium alkoxide.

[0028] The filtrate M in S7 is applied to the filtrate K in S6.

[0029] The filtrate in S3 was used as mother liquor in the next batch of reaction.

[0030] The organic solvent F in S4 is any one or more of dioxane, acetone, acetonitrile, dimethylformamide, dimethyl sulfoxide, ethyl acetate, anhydrous ethanol, methyl ethyl ketone, isopropanol, and tetrahydrofuran.

[0031] Steps S4, S5, S6, and S7 need to be protected from light.

[0032] The reaction temperature in S5 is 0-10°C.

[0033] The filter cake in S6 is potassium iodide or sodium iodide.

[0034] The filtrate M in S7 is a saturated solution of N-iodosuccinimide, which is applied to the next batch and continued to concentrate to improve the yield.

[0035] Beneficial effects of the present invention:

[0036] 1. The present invention uses cheap and readily available raw materials, thus reducing product costs;

[0037] 2. The process adopts a recycling method, which produces almost no three wastes. The iodide filter cake can be used as sodium iodide or potassium iodide products after drying, and all inspections are qualified;

[0038] 3. The reaction conditions are mild. The two reactions can be completed at room temperature and lower temperature respectively, which reduces energy consumption, reduces the requirements for reaction equipment, and improves process safety.

[0039] 4. The reaction yield is improved. After the filtrate is applied, the succinimide salt yield is over 99%, the iodine recovery rate is over 95%, and the total yield is over 94%;

[0040] 5. The traditional method of preparing NIS by reacting succinimide with silver oxide requires high temperature and long reflux reaction, and it must be placed in a dark place overnight, and the maximum yield is about 85%. However, this reaction is highly efficient, has a short reaction time, and is under milder conditions. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 This is a process flow chart of steps S1-S3 of the present invention;

[0042] Figure 2 This is a process flow chart of steps S4-S7 of the present invention. DETAILED DESCRIPTION

[0043] The present invention is further illustrated by the following examples. It should be correctly understood that the examples of the present invention are only used to illustrate the present invention, rather than to limit the present invention. Therefore, simple improvements to the present invention based on the method of the present invention fall within the scope of protection claimed by the present invention.

[0044] Reaction equation

[0045]

[0046] Example 1 (not applied)

[0047] 33 g of succinimide was added to 100 g of water to prepare a succinimide solution; 42 g of 32% sodium hydroxide solution was added dropwise to the solution at room temperature, and the pH was adjusted to 8-9. After stirring for 60 minutes, the pH was re-measured. If the pH remained unchanged, a succinimide sodium salt solution was obtained; the succinimide sodium salt solution was concentrated until a large amount of solid precipitated, then cooled and filtered, and the filter cake was dried to obtain 32.91 g of succinimide sodium salt. The yield of this step was about 80%; the filtrate was used as a mother liquor in the next batch reaction; under light-proof conditions, 128 g of dioxane was used to dissolve 67 g of refined iodine to obtain an iodine solution, and the iodine solution was used. 128 g of sodium succinimide was dissolved in dioxane to obtain a sodium succinimide solution; the sodium succinimide solution was added dropwise to the iodine solution at 0-10° C. in the dark, with stirring for 30 minutes. After the addition was complete, the solution was stirred at 0-10° C. for 2 hours; the reaction solution was filtered in the dark, and the filter cake containing inorganic iodide was dried and sent for inspection; the filtrate was concentrated in the dark until a large amount of solid precipitated, then cooled and filtered. The filter cake was dried in the dark under vacuum to obtain 45.15 g of product NIS. The NIS content was found to be 99.58%, resulting in a yield of 75%. The filtrate was used in the next batch of concentrated solution.

[0048] Example 2 application

[0049] 33 g of succinimide was added to 100 g of water to prepare a saturated solution of succinimide, and the sodium succinimide filtrate in Example 1 was added; 42 g of 32% sodium hydroxide solution was added dropwise to the solution, the pH was adjusted to 8-9, and the pH was repeated after stirring for 60 min. The pH remained unchanged to obtain a sodium succinimide solution; the sodium succinimide solution was concentrated to a large amount of solid precipitated, then cooled and filtered, and the filter cake was dried to obtain 40.77 g of sodium succinimide, with a yield of 99.1% in this step; the filtrate was used as a mother liquor in the next batch of reactions; under light-proof conditions, 128 g of dioxane was used to dissolve 83.76 g of refined iodine to obtain an iodine solution, which could not be completely dissolved and did not affect the reaction (the dissolved iodine was consumed while the solvent dissolved the iodine during the reaction). 45.57 g of sodium succinimide was dissolved in 128 g of dioxane to obtain a sodium succinimide solution; the sodium succinimide solution was added dropwise to the iodine solution at 0-10° C. in the dark, with stirring during the addition, for 30 minutes. After the addition was complete, the solution was stirred at 0-10° C. for 2 hours; the reaction solution was filtered in the dark, and the filter cake containing inorganic iodide was dried and sent for inspection; the filtrate was concentrated in the dark until a large amount of solid precipitated, then cooled and filtered. The filter cake was dried in the dark under vacuum to obtain 71.15 g of product NIS with an NIS content of 99.66% and a yield of 95%. The filtrate was used in the next batch of concentrated solution.

[0050] Example 3

[0051] 33 g of succinimide was added to 100 g of water to prepare a saturated succinimide solution; 37.7 g of 50% potassium hydroxide solution was added dropwise to the solution at room temperature, and the pH was adjusted to 8-9. After stirring for 60 minutes, the pH was re-measured. If the pH remained unchanged, a potassium succinimide solution was obtained; the potassium succinimide solution was concentrated until a large amount of solid precipitated, then cooled and filtered, and the filter cake was dried to obtain 38.69 g of potassium succinimide, with a yield of 83% in this step; the filtrate was used as a mother liquor in the next batch reaction; under light-proof conditions, 128 g of dioxane was used to dissolve 70.15 g of refined iodine to obtain an iodine solution, and 128 g of dioxane was used to dissolve the succinimide The potassium succinimide solution was obtained by adding potassium amine to the iodine solution; the potassium succinimide solution was added dropwise to the iodine solution at 0-10°C under light-proof conditions, with stirring during the addition, for 30 minutes, and after the addition was completed, the solution was stirred at 0-10°C for 2 hours; the reaction solution was filtered under light-proof conditions, and the filter cake containing inorganic iodide was dried and sent for inspection; the filtrate was concentrated in the dark until a large amount of solid precipitated, then cooled and filtered, and the filter cake was dried in the dark under vacuum to obtain 48.26 g of product NIS with an NIS content of 99.49%. The yield of this step was 77.22%, and the filtrate was used.

[0052] Example 4

[0053] 33 g of succinimide was added to 100 ml of methanol to prepare a saturated succinimide solution; 60 g of 30% sodium methoxide solution was added dropwise to the solution at room temperature and stirred for 60 min to obtain a sodium succinimide solution; the sodium succinimide solution was concentrated until a large amount of solid precipitated, then cooled and filtered, and the filter cake was dried to obtain 33.81 g of sodium succinimide, with a yield of 82.2% in this step; the filtrate was used as a mother liquor in the next batch of reactions; under light-proof conditions, 128 g of dioxane was used to dissolve 69.48 g of refined iodine to obtain an iodine solution, and 128 g of dioxane was used to dissolve sodium succinimide to obtain succinyl succinate. Sodium imide solution; under light-proof conditions, at 0-10°C, add the sodium succinimide solution dropwise to the iodine solution while stirring for 30 minutes. After the addition is complete, stir at 0-10°C for 2 hours; under light-proof conditions, filter the reaction solution, dry the filter cake containing inorganic iodide, and then send it for inspection; the filtrate is concentrated in the dark until a large amount of solid precipitates, then cooled and filtered, and the filter cake is dried in the dark under vacuum to obtain 47.1g of product NIS with an NIS content of 99.56%. The yield of this step is 76%, and the filtrate is used.

[0054] Finally, it should be noted that the above-described embodiments merely represent several implementation methods of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made by a person skilled in the art without departing from the spirit of the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the patent for this invention should be based on the appended claims.

Claims

1. A method for synthesizing N-iodosuccinimide, characterized in that: The following steps are involved: S1. Add succinimide finished product to 2.9-3.1 times the mass of water to form a saturated solution of succinimide; S2. A strong base solution was added dropwise to a saturated solution of succinimide, and the pH was adjusted to 8 to 9, with a molar ratio of succinimide to the strong base of 1 to 1.

01. The reaction was stirred for 60 minutes while maintaining the pH constant to obtain a sodium succinimide solution. S3. The sodium succinimide salt solution was concentrated and filtered to obtain solid sodium succinimide and the filtrate, and the solid sodium succinimide was dried; S4. Under light-shielding conditions, an iodine reagent was dissolved in an organic solvent F to obtain an iodine reagent solution G, wherein the iodine reagent was 0.95-1.02 times the molar amount of sodium succinimide, and the solid sodium succinimide obtained in S3 was dissolved in an organic solvent F to obtain a sodium succinimide solution H; S5. Under light-proof conditions, at -5 to 30 ° C, the sodium succinimide solution H was added dropwise to the iodine reagent solution G, with stirring while adding, and the addition was continued for 30 min. After the addition was completed, the reaction solution I was obtained by stirring at -5 to 30 ° C for 2 h; S6. Protect from light, filter the reaction solution I, filter cake J is inorganic iodide; filtrate K is the product phase; S7. Concentrate the filtrate K in the dark until a large amount of solid precipitates, then cool and filter to obtain filter cake L and filtrate M. The filter cake L is dried in a vacuum oven in the dark to obtain product NIS.

2. The method according to claim 1, characterized in that The alkali in the strong alkali solution in S2 is selected from any one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium alkoxide, and potassium alkoxide.

3. The method according to claim 1, characterized in that The filtrate M in S7 is applied to the filtrate K in S6.

4. The method according to claim 1, wherein The filtrate in S3 was used as mother liquor in the next batch of reaction.

5. The method according to claim 1, wherein The organic solvent F in S4 is any one or more of dioxane, acetone, acetonitrile, dimethylformamide, dimethyl sulfoxide, ethyl acetate, anhydrous ethanol, methyl ethyl ketone, isopropanol, and tetrahydrofuran.

6. The method according to claim 1, characterized in that Steps S4, S5, S6, and S7 need to be protected from light.

7. The method according to claim 1, characterized in that The reaction temperature in S5 is 0-10°C.

8. The method according to claim 1, characterized in that The filter cake in S6 is potassium iodide or sodium iodide.

9. The method according to claim 7, characterized in that The filtrate M in S7 is a saturated solution of N-iodosuccinimide, which is applied to the next batch and continued to concentrate to improve the yield.

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