A method for synthesizing N-hydroxyimide compounds

Abstract

The present invention relates to a method for synthesizing N-hydroxyimide compounds, which has the advantages of low cost, no solid waste salt, no generation of saline wastewater, simple preparation process and environmental protection. The technical scheme adopted by the present invention is to use high-concentration hydrogen peroxide as an oxidant, and under the action of a mesoporous titanium silicon molecular sieve supported iron oxide (Fe2O3 / Ti-Si-O) catalyst, oxidize the imide in a suitable solvent under suitable temperature and time conditions to form an N-hydroxyimide compound.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a method for synthesizing N-hydroxyimide compounds. Background Art

[0002] N-hydroxyimide compounds are an important class of chemical raw materials and functional chemicals, and are widely used in organic synthesis, industrial catalysis, and chemical energy storage. For example, N-hydroxyphthalimide is widely used in catalytic oxidation reactions to synthesize alcohols, acids, aldehydes, and peroxide compounds with high selectivity; N-hydroxypyrazine dicarboximide can be used to synthesize oxime compounds with anticancer and antiviral effects; N-hydroxysuccinimide can be used as an electrochemical electron conductor.

[0003] The traditional synthesis method of N-hydroxy imide is to conduct condensation reaction between dicarboxylic anhydride compounds and hydroxylamine hydrochloride under the action of an acid-binding agent to obtain the N-hydroxy imide product. For example, the synthesis method disclosed in Chinese patent CN1051170 (synthesis method of aminooxy fatty carboxylic acid) uses phthalic anhydride and hydroxylamine hydrochloride as raw materials, adds excessive sodium carbonate as an acid-binding agent, promotes the formation of N-hydroxyphthalimide, and the yield reaches 80-85%; the preparation process produces stoichiometric sodium chloride solid waste, and the water washing during product refining will produce a large amount of difficult-to-treat salt-containing wastewater. Chinese patent CN105111128A (a preparation method of N-hydroxyphthalimide) proposes to use triethylamine as an acid-binding agent to promote the formation of N-hydroxyphthalimide, and the yield reaches 90%. It also produces stoichiometric triethylamine hydrochloride solid waste, but it is easier to handle than the aforementioned NaCl solid waste, but the production cost increases.

[0004] In order to avoid the generation of "waste salt" and salt-containing wastewater, Chinese patent CN105348139A (Synthesis process of O-3-chloro-2-propenylhydroxylamine) proposes to use highly active phthaloyl chloride and hydroxylamine hydrochloride to react at low temperature in a dichloromethane medium to generate N-hydroxylamine phthalimide with a yield of 95%. The preparation process does not generate a large amount of solid waste (waste salt), but releases a large amount of HCl gas, and the raw material phthaloyl chloride is relatively expensive. Summary of the invention

[0005] In order to solve the above problems, the purpose of the present invention is to provide a clean method for synthesizing N-hydroxyimide compounds, which has the advantages of low cost, no solid waste salt and salt-containing wastewater, simple preparation process and environmental protection.

[0006] To achieve the above object, the technical solution adopted by the present invention is:

[0007] A method for synthesizing N-hydroxyimide compounds, using hydrogen peroxide with a mass concentration of not less than 50% as an oxidant, in the presence of Fe 2 O 3 / Ti-Si-O catalyst, the imide compounds are oxidized into N-hydroxyimide compounds in an organic solvent at a temperature of 45°C to 80°C. 2 O 3 / Ti-Si-O catalyst is a mesoporous titanium silicon molecular sieve supported iron oxide catalyst.

[0008]

[0009] Preferably, the reaction temperature is 55°C to 70°C.

[0010] Preferably, the organic solvent is selected from tert-butyl alcohol, acetonitrile, ethylene glycol dimethyl ether or diethylene glycol dimethyl ether.

[0011] Preferably, the imide compound is selected from the compound shown in formula I, 3,4-pyridinedicarboximide, 2,3-pyrazinedicarboximide, succinimide,

[0012]

[0013] Wherein, R is selected from halogen, hydroxyl, carboxyl or hydrogen.

[0014]

[0015] Preferably, the mass concentration of the hydrogen peroxide is 50% to 75%.

[0016] Preferably, the molar ratio of the hydrogen peroxide to the imide compound is selected from 1.35-1.65:1.0.

[0017] Preferably, Fe 2 O 3 The Ti-Si-O catalyst accounts for 9-15% of the weight of the imide compound.

[0018] Preferably, the average pore size of the Ti-Si-O is 4 to 9 nm; the molar ratio of titanium to silicon atoms is 2 to 4:100; Fe 2 O 3 The weight loading on Ti-Si-O is 5-12%. The loading is Fe 2 O 3 Mass / (Fe 2 O 3 / Ti-Si-O) mass.

[0019] Preferably, the average pore size of the Ti-Si-O is 4 to 7.9 nm;

[0020] Preferably, the specific steps of the synthesis method are:

[0021] (5) dissolving the imide compound in an organic solvent, and then adding a Fe2O3 / Ti-Si-O catalyst;

[0022] (6) Stir thoroughly, control the temperature, add hydrogen peroxide dropwise, and continue to control the temperature and react after the addition is complete;

[0023] (7) After the reaction is completed, the catalyst is removed by filtration, the solvent is recovered by distillation under reduced pressure, and the by-produced water is distilled off to obtain a solid crude product;

[0024] (8) The crude product is dissolved in ethanol at about 50°C to 80°C, cooled in an ice-water bath to crystallize, filtered, and dried by rotary evaporation at room temperature to obtain N-hydroxyimide compounds.

[0025] Preferably, in step (2), the hydrogen peroxide addition time is controlled within 2 to 4 hours, and after the addition is completed, the temperature is controlled to react for 4 to 10 hours.

[0026] Beneficial effects:

[0027] (1) The N-hydroxyimide compounds are synthesized by hydrogen peroxide catalytic oxidation method, which does not produce stoichiometric waste salt (solid waste) or a large amount of salt-containing wastewater, and the preparation process is clean and environmentally friendly.

[0028] (2) No stoichiometric acid-binding agent is added during the preparation process, and no complicated environmental treatment measures are required, so the preparation cost is low.

[0029] (3) The preparation process does not use highly toxic raw materials (such as hydroxylamine hydrochloride), and the by-product is H 2 O, so the production process has little harm to human body and environment and has the characteristics of green chemical process. DETAILED DESCRIPTION

[0030] The present invention can be further described by the following examples, which are intended to illustrate but not to limit the present invention. Any person skilled in the art will appreciate that these examples do not limit the present invention in any way and that appropriate modifications and data conversions may be made thereto without violating the spirit of the present invention and departing from the scope of the present invention.

[0031] Example 1

[0032] 1#Fe 2 O 3 / Ti-Si-O catalyst preparation:

[0033] After 46g of concentrated hydrochloric acid, 140g of water and 14g of glutaric acid were mixed to form a transparent solution, 41g of tetraethyl silicate and 1.5g of tetrabutyl titanate were added into the mixture within 2 hours under sufficient mechanical stirring. After the addition, the mixture was stirred for 12 hours, and the obtained sol was placed in an oven at 150°C for 12 hours to obtain a transparent dry glue. After the dry glue was ground, it was calcined at 500°C for 6 hours to obtain 11.6g of mesoporous titanium silicon molecular sieve (Ti-Si-O) with a specific surface area of ​​794m 2 / g, pore volume 0.83mL / g, average pore diameter 4.1nm, Ti:Si=2.2:100 (molar ratio).

[0034] 10 g of the prepared mesoporous Ti-Si-O molecular sieve was immersed in a solution of 6 g of ferric nitrate nonahydrate and 16 g of water, and ultrasonically treated at 60 °C until the water was basically evaporated; then baked at 120 °C for 4 h, and finally calcined at 500 °C for 2 h to obtain 11.2 g of Fe 2 O 3 / Ti-Si-O catalyst, where Fe 2 O 3 The weight loading is about 12% and the average pore size is 4.0nm. Labeled as 1#Fe 2 O 3 / Ti-Si-O catalyst.

[0035] Example 2

[0036] 2#Fe 2 O 3 / Ti-Si-O catalyst preparation:

[0037] Add 800g water, 46g concentrated HCl, 24g polyether P123 (template) and 28g n-butanol to the reaction bottle. After stirring at 35°C for 2h, add a mixture of 53g tetraethyl silicate and 2.6g tetrabutyl titanate dropwise in 1h. Then stir at 35°C for 4h and react at 100°C for 24h. Then filter, dry at 120°C, and calcine at 550°C for 6h to obtain 15.4g mesoporous Ti-Si-O molecular sieve with a specific surface area of ​​782.2m 2 / g, pore volume 1.1 mL / g, average pore diameter 5.6 nm, Ti:Si=3.1:100 (molar ratio).

[0038] Take 15g of the prepared mesoporous Ti-Si-O molecular sieve, immerse it in a solution formed by 6.2g of ferric nitrate nonahydrate and 20g of water, and treat it with ultrasound at 60℃ until the water is basically evaporated. Then bake it at 120℃ for 4h, and finally calcine it at 500℃ for 2h to obtain 15.9g Fe 2 O 3 / Ti-Si-O catalyst, where Fe 2 O 3The weight loading is about 8%, and the average pore size is 5.5nm. Labeled as 2#Fe 2 O 3 / Ti-Si-O catalyst.

[0039] Example 3

[0040] 3#Fe 2 O 3 / Ti-Si-O catalyst preparation:

[0041] Add 850g water, 50g concentrated HCl, 28g polyether F127 (template) and 40g mesitylene into the reaction bottle. After stirring at 35℃ for 2h, add a mixture of 53g tetraethyl silicate and 3.5g tetrabutyl titanate dropwise in 1h. Then stir at 35℃ for 4h and react at 100℃ for 24h. Then filter, dry at 120℃, and calcine at 550℃ for 6h to obtain 15.6g mesoporous Ti-Si-O molecular sieve with a specific surface area of ​​603.4m 2 / g, pore volume 1.2mL / g, average pore diameter 7.9nm, Ti:Si=4.0:100 (molar ratio).

[0042] Take 15g of the prepared mesoporous Ti-Si-O molecular sieve, immerse it in a solution formed by 3.9g of ferric nitrate nonahydrate and 20g of water, and treat it with ultrasound at 60℃ until the water is basically evaporated. Then bake it at 120℃ for 4h, and finally calcine it at 500℃ for 2h to obtain 15.5g Fe 2 O 3 / Ti-Si-O catalyst, where Fe 2 O 3 The weight loading is about 5%, and the average pore size is 7.9nm. Labeled as 3#Fe 2 O 3 / Ti-Si-O catalyst.

[0043] Example 4

[0044] 1#Fe 2 O 3 / Ti-Si-O catalyst catalyzes the oxidation of phthalimide with hydrogen peroxide to synthesize N-hydroxyphthalimide:

[0045]

[0046] Add 30g phthalimide (0.2mol), 90g acetonitrile, 2.4g 1#Fe 2 O 3 / Ti-Si-O catalyst, under sufficient stirring, at 45 ° C, 2 h add 15g of 75% weight concentration hydrogen peroxide (0.33mol), after the addition is completed, continue to react at 45 ° C for 10 h.

[0047] After the reaction, the catalyst was filtered off, acetonitrile was recovered by vacuum distillation, and the by-product water was distilled off to obtain a solid crude product. 80g of anhydrous ethanol was used to dissolve the crude product at 70°C, and then placed in an ice-water bath for cooling and crystallization, suction filtration, and rotary evaporation drying at room temperature to obtain 22.6g of N-hydroxyphthalimide product, with a purity of 99.6% according to high pressure liquid chromatography analysis, and a product yield of 69.0%. 1 H-NMR (DMSO-d6) δ: 10.82 (s, 1H), 7.84 (s, 4H).

[0048] Example 5

[0049] 2#Fe 2 O 3 / Ti-Si-O catalyst catalyzes the oxidation of phthalimide with hydrogen peroxide to synthesize N-hydroxyphthalimide:

[0050] Add 30g phthalimide (0.2mol), 90g ethylene glycol dimethyl ether, 3.6g 2#Fe 2 O 3 / Ti-Si-O catalyst, under sufficient stirring, 15.1g of 70% weight concentration hydrogen peroxide (0.31mol) was added dropwise at 55°C for 3h, and the reaction was continued at 55°C for 8h after the addition was completed.

[0051] After the reaction, the catalyst was filtered off, ethylene glycol dimethyl ether was recovered under reduced pressure, and the by-product water was distilled off to obtain a solid crude product. The crude product was dissolved in 80g of anhydrous ethanol at 70°C, then placed in an ice-water bath for cooling and crystallization, filtered, and dried by rotary evaporation at room temperature to obtain 23.2g of N-hydroxyphthalimide product, with a purity of 99.2% according to high pressure liquid chromatography analysis, and a product yield of 70.6%. 1 H-NMR (DMSO-d6) δ: 10.82 (s, 1H), 7.84 (s, 4H).

[0052] Example 6

[0053] 3#Fe 2 O 3 / Ti-Si-O catalyst catalyzes the oxidation of phthalimide with hydrogen peroxide to synthesize N-hydroxyphthalimide:

[0054] Add 30g phthalimide (0.2mol), 120g tert-butyl alcohol, 4.5g 3#Fe 2 O 3 / Ti-Si-O catalyst, under sufficient stirring, 16.5g of 60% weight concentration hydrogen peroxide (0.29mol) was added dropwise at 70℃ for 4h, and the reaction was continued at 70℃ for 6h after the addition was completed.

[0055] After the reaction is completed, the catalyst is filtered off, tert-butyl alcohol is recovered under reduced pressure, and the by-product water is distilled off to obtain a solid crude product. The crude product is dissolved in 80g of anhydrous ethanol at 70°C, then placed in an ice-water bath for cooling and crystallization, filtered with suction, and dried by rotary evaporation at room temperature to obtain 22.7g of N-hydroxyphthalimide product, with a purity of 99.3% according to high pressure liquid chromatography analysis, and a product yield of 69.1%, 1H-NMR (DMSO-d6) δ: 10.82 (s, 1H), 7.84 (s, 4H).

[0056] Example 7

[0057] 2#Fe 2 O 3 / Ti-Si-O catalyst catalyzes the oxidation of 3,4-pyridinedicarboximide with hydrogen peroxide to synthesize N-hydroxy-3,4-pyridinedicarboximide:

[0058]

[0059] Add 30g 3,4-pyridinedicarboximide (0.2mol), 90g diethylene glycol dimethyl ether, 3.6g 2#Fe 2 O 3 / Ti-Si-O catalyst, under sufficient stirring, 30.3g of 50% weight concentration hydrogen peroxide (0.27mol) was added dropwise at 80℃ for 4h, and the reaction was continued at 80℃ for 4h after the addition was completed.

[0060] After the reaction, the catalyst was filtered off, diethylene glycol dimethyl ether was recovered under reduced pressure, and the by-product water was distilled off to obtain a solid crude product. The crude product was dissolved in 80g of anhydrous ethanol at 70°C, then placed in an ice-water bath for cooling and crystallization, filtered, and dried by rotary evaporation at room temperature to obtain 21.4g of N-hydroxy-3,4-pyridinedicarboximide product, with a purity of 99.3% according to high pressure liquid chromatography analysis, and a product yield of 64.8%. 1 H-NMR (DMSO-d6) δ: 11.04 (s, 1H), 8.94 (m, 1H), 8.24 (m, 1H), 7.77 (m, 1H).

[0061] Example 8

[0062] 2#Fe 2 O 3 / Ti-Si-O catalyst catalyzes the oxidation of 2,3-pyrazinedicarboximide with hydrogen peroxide to synthesize N-hydroxy-2,3-pyrazinedicarboximide:

[0063]

[0064] Add 31g 2,3-pyrazinedicarboximide (0.2mol), 90g acetonitrile, 3.7g 2#Fe 2 O 3 / Ti-Si-O catalyst, under sufficient stirring, 30.3g of 50% weight concentration hydrogen peroxide (0.27mol) was added dropwise at 65°C for 3h, and the reaction was continued at 65°C for 8h after the addition was completed.

[0065] After the reaction was completed, the catalyst was filtered off, acetonitrile was recovered under reduced pressure, and the by-product water was distilled off to obtain a solid crude product. The crude product was dissolved in 80g of anhydrous ethanol at 70°C, then placed in an ice-water bath for cooling and crystallization, filtered, and dried by rotary evaporation at room temperature to obtain 20.9g of N-hydroxy-2,3-pyrazinedicarboximide product, with a purity of 98.5% according to high pressure liquid chromatography analysis, and a product yield of 62.4%. 1 H-NMR (DMSO-d6) δ: 11.28 (s, 1H), 8.95 (s, 2H).

[0066] Example 9

[0067] 1#Fe 2 O 3 / Ti-Si-O catalyst catalyzes the oxidation of 4-chlorophthalimide with hydrogen peroxide to synthesize N-hydroxy-4-chlorophthalimide:

[0068] Add 37g 4-chloro-o-dicarboximide (0.2mol), 90g acetonitrile, 3.4g 1#Fe 2 O 3 / Ti-Si-O catalyst, under sufficient stirring, 15.1g of 70% weight concentration hydrogen peroxide (0.31mol) was added dropwise at 65°C for 3h, and the reaction was continued at 65°C for 6h after the addition was completed.

[0069] After the reaction was completed, the catalyst was filtered off, acetonitrile was recovered under reduced pressure, and the by-product water was distilled off to obtain a solid crude product. The crude product was dissolved in 80g of anhydrous ethanol at 70°C, then placed in an ice-water bath for cooling and crystallization, filtered, and dried by rotary evaporation at room temperature to obtain 28.7g of N-hydroxy-4-chlorophthalimide product, with a purity of 99.1% according to high pressure liquid chromatography analysis, and a product yield of 72.0%. 1 H-NMR (DMSO-d6) δ: 10.89 (s, 1H), 8.84 (s, 1H), 8.26 (d, 1H), 8.17 (d, 1H).

[0070] Comparative Example 1

[0071] N-hydroxyphthalimide was prepared according to the method described in Chinese patent CN1239715 (synthesis method of N-hydroxyphthalimide).

[0072] Dissolve 25.0 g of phthalic anhydride in 100 mL of a hydrated organic solvent (containing organic solvent C 4 H 8 O 2 50%, v / v), then add 13.0g of hydroxylamine hydrochloride, react at 85-90°C for 4h. After the reaction is completed, evaporate the organic solvent under reduced pressure and dry to obtain 24.7g of white solid with a yield of 90%.

[0073] Comparative Example 1 uses highly toxic hydroxylamine hydrochloride as an acid-binding agent to promote the formation of N-hydroxyphthalimide. The production process is highly harmful to the human body and the environment and does not have the characteristics of a green chemical process.

[0074] Comparative Example 2

[0075] N-hydroxyphthalimide was prepared according to the method described in Chinese patent CN105111128A (a method for preparing N-hydroxyphthalimide).

[0076] 29.6 g of phthalic anhydride and 13.9 g of hydroxylamine hydrochloride were put into 200 mL of isopropanol, and 20.2 g of triethylamine was slowly added to the above solution within 30 min under room temperature and stirring conditions, and then reacted at 80°C for 1.5 h. After the reaction was completed, isopropanol and triethylamine were evaporated under reduced pressure, and then washed with water and dried at 60°C for 24 h to obtain 29.4 g of white solid N-hydroxyphthalimide with a yield of 90.1% and a purity of 98.6%.

[0077] Comparative Example 2 uses triethylamine as an acid-binding agent to promote the formation of N-hydroxyphthalimide, but produces stoichiometric triethylamine hydrochloride solid waste, which requires complex environmental protection treatment measures, so the preparation cost is high.

[0078] By comparing with Comparative Examples 1 and 2, it can be seen that the technical method of the present invention adopts hydrogen peroxide catalytic oxidation method to synthesize N-hydroxyimide compounds, does not produce stoichiometric waste salt (solid waste), and does not produce a large amount of salt-containing wastewater, and the preparation process is clean and environmentally friendly; no stoichiometric acid binding agent is added in the preparation process, and highly toxic hydroxylamine hydrochloride is not used, and the by-product is H 2 O, the production process has little harm to human body and environment, and has the characteristics of green chemical process.

Claims

1. A method for synthesizing N-hydroxyimide compounds, characterized in that: Using hydrogen peroxide with a mass concentration of not less than 50% as an oxidant, under the action of a Fe2O3 / Ti-Si-O catalyst, oxidizing the imide compound in an organic solvent at a temperature of 45°C to 80°C to form an N-hydroxyimide compound; The imide compound is selected from the compound shown in formula I, 3,4-pyridinedicarboximide or 2,3-pyrazinedicarboximide, Wherein, R is selected from halogen, hydroxyl, carboxyl or hydrogen, and the Fe2O3 / Ti-Si-O catalyst is a mesoporous titanium silicon molecular sieve loaded with iron oxide catalyst.

2. The synthesis method according to claim 1, characterized in that The reaction temperature is 55°C to 70°C.

3. The synthesis method according to claim 1, characterized in that The organic solvent is selected from tert-butyl alcohol, acetonitrile, ethylene glycol dimethyl ether or diethylene glycol dimethyl ether.

4. The synthesis method according to claim 1, characterized in that The mass concentration of the hydrogen peroxide is 50% to 75%.

5. The synthesis method according to claim 1, characterized in that The molar ratio of the hydrogen peroxide to the imide compound is selected from 1.35 to 1.65:1.

0.

6. The synthesis method according to claim 1, characterized in that The Fe2O3 / Ti-Si-O catalyst accounts for 9-15% of the weight of the imide compound.

7. The synthesis method according to claim 1, characterized in that The average pore size of the Ti-Si-O is 4-9 nm; the molar ratio of titanium to silicon atoms is 2-4:100; and the weight loading of Fe2O3 on the Ti-Si-O is 5-12%.

8. The synthesis method according to any one of claims 1 to 7, characterized in that: The specific steps of the synthesis method are: The imide compound is dissolved in an organic solvent, and then a Fe2O3 / Ti-Si-O catalyst is added; Stir thoroughly, control the temperature, add hydrogen peroxide dropwise, and continue to control the temperature and react after the addition is complete; After the reaction is completed, the catalyst is filtered off, the solvent is recovered by distillation under reduced pressure, and the by-produced water is distilled off to obtain a solid crude product; The crude product is dissolved in ethanol at about 50°C to 80°C, placed in an ice-water bath to cool and crystallize, filtered, and dried by rotary evaporation at room temperature to obtain N-hydroxyimide compounds.

9. The synthesis method according to claim 8, characterized in that In step (2), the hydrogen peroxide addition time is controlled within 2 to 4 hours, and after the addition is completed, the temperature is controlled to react for 4 to 10 hours.

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