A kind of synthetic method of N-hydroxyphthalimide

Abstract

The invention discloses a method for synthesizing N-hydroxyphthalimide, which belongs to the field of chemical synthesis. In an organic solvent, phthalimide reacts with 60-75% hydrogen peroxide under the action of a catalyst, molybdenum vanadium oxide, to obtain N-hydroxyphthalimide. The preparation method of the invention has low cost, the catalyst can be recycled, the synthesis process is simple, no waste salt or waste brine is generated, and it is more environmentally friendly.

Description

Technical Field

[0001] The invention belongs to the field of chemical synthesis, and specifically relates to a method for synthesizing N-hydroxyphthalimide. 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 view of the shortcomings of the prior art in synthesizing N-hydroxyimide compounds, such as high cost, generation of solid waste salt and saline wastewater, and complex preparation process, the present invention aims to provide a clean method for synthesizing N-hydroxyimide compounds, which has the advantages of low cost, no generation of solid waste salt and saline wastewater, simple preparation process, and environmental protection.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0007] A method for synthesizing N-hydroxyphthalimide comprises the following steps: in an organic solvent, phthalimide is reacted with 60-75% hydrogen peroxide under the action of a catalyst, molybdenum vanadium oxide, to obtain N-hydroxyphthalimide.

[0008] Preferably, the molar ratio of molybdenum to vanadium in the molybdenum-vanadium oxide is 4 to 6:1.

[0009] Preferably, the molar ratio of hydrogen peroxide to phthalimide is 1.2-1.5:1.0.

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

[0011] Preferably, the reaction temperature of the synthesis method is 50°C to 80°C.

[0012] Preferably, hydrogen peroxide is slowly added to the organic solvent containing phthalamide. The "slowly" mentioned here is a method well known in the chemical field, such as slow dripping.

[0013] Preferably, the catalyst is molybdenum-vanadium oxide supported on mesoporous silica (ie, V2O5-MoO3 / m-SiO2) or molybdenum-vanadium oxide supported on mesoporous ceria (ie, V2O5-MoO3 / m-CeO2).

[0014]

[0015] Preferably, the loading amount of molybdenum-vanadium oxide in the catalyst is 10-20%; the loading amount here refers to the weight ratio of molybdenum-vanadium oxide to the mass ratio of mesoporous silica or mesoporous ceria.

[0016] The average pore diameter of the mesoporous silica or mesoporous cerium dioxide is 4-8 nm, and the average pore volume is 0.55-1.0 mL / g.

[0017] Preferably, when the catalyst is mesoporous ceria-supported molybdenum-vanadium oxide, the synthesis method of the catalyst is:

[0018] (1) Add triethylamine or triethylenetetramine to Ce(SO4)4 solution and stir to obtain a yellow solution;

[0019] (2) raising the temperature to 50-80° C., adding aqueous ammonia to the solution obtained in step (1) to carry out a reaction;

[0020] (3) filtering the intermediate product obtained in step (2), and then calcining at 400-500° C. for 2-6 hours to obtain mesoporous cerium dioxide;

[0021] (4) adding the mesoporous cerium dioxide obtained in step (3) to an aqueous solution of ammonium metavanadate and hydrated ammonium heptamolybdate, and evaporating the water at 50-80° C. to obtain an impregnated product;

[0022] (5) Calcine the impregnated material at 400-600°C for 2-6 hours to obtain a catalyst.

[0023] Preferably, the amount of the catalyst used is 8-15% by weight of phthalimide.

[0024] Beneficial effects:

[0025] (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.

[0026] (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.

[0027] (3) The preparation process does not use highly toxic raw materials (such as hydroxylamine hydrochloride), the by-product is H2O, and the production process is green and environmentally friendly. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 Example 4 Product NHPI HPLC Chromatogram

[0029] Figure 2 Example 4 Product NHPI Hydrogen Spectrum 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] The raw materials used in the examples were purchased from the market:

[0032] First, three catalysts were prepared: catalyst #1, catalyst #2 and catalyst #3.

[0033] Example 1

[0034] 1# Catalyst Preparation:

[0035] Preparation of m-CeO2: Add 0.3 mol triethylamine to 750 mL of 0.2 mol / L Ce(SO4)4 solution, stir vigorously until an orange solution is obtained, and add 110 mL of 25% ammonia water at 80°C. Then stir at 80°C for 12 h, filter, wash the filter cake with deionized water 5 times (200 mL of deionized water each time), and calcine the filter cake in air at 500°C for 2 h. 21.8 g of 526 m 2 / g, pore diameter of 4.2nm, and pore volume of 0.55mL / g of m-CeO2.

[0036] Preparation of V2O5-MoO3 / m-CeO2 catalyst: Add 0.0031mol ammonium metavanadate and 0.0018mol hydrated ammonium heptamolybdate to 30mL deionized water, and dissolve them by ultrasonication at room temperature for 10min. Add 20g of the prepared m-CeO2, and then ultrasonicate at 60℃ until the water is basically evaporated. The impregnated material is placed in a furnace and roasted at 500℃ for 4h to obtain 22.1g of V2O5-MoO3 / m-CeO2 catalyst. According to the feed amount, the active component loading is 10.5% (relative to the weight of the carrier m-CeO2), where Mo:V=4:1 (molar ratio). Named as catalyst #1.

[0037] Example 2

[0038] 2# Catalyst Preparation:

[0039] Preparation of m-CeO2: Add 0.35 mol of triethylenetetramine to 750 mL of 0.2 mol / L Ce(SO4)4 solution, stir vigorously until an orange solution is formed, and add 100 mL of 25% ammonia water at 50°C. Then stir at 65°C for 12 hours, filter, wash the filter cake with deionized water 6 times (200 mL of deionized water each time), and calcine the filter cake in air at 400°C for 6 hours. 22.3 g of m-CeO2 with a specific surface area of ​​568 m 2 / g, pore diameter of 5.8nm, and pore volume of 0.82mL / g of m-CeO2.

[0040] Preparation of V2O5-MoO3 / m-CeO2 catalyst: Add 0.00371mol ammonium metavanadate and 0.00262mol hydrated ammonium heptamolybdate to 30mL deionized water, and dissolve them by ultrasonication at room temperature for 10min. Add 20g of the prepared m-CeO2, and then ultrasonicate at 50℃ until the water is basically evaporated. Place the impregnated material in a furnace and roast it at 400℃ for 6h to obtain 23.2g of V2O5-MoO3 / m-CeO2 catalyst. According to the feed amount, the active component loading is 16% (relative to the weight of the carrier m-CeO2), where Mo:V=5:1 (molar ratio). Named as catalyst 2#.

[0041] Example 3

[0042] 3# Catalyst Preparation:

[0043] Preparation of m-CeO2: Add 0.35 mol triethylenetetramine and 15 g octadecyltrimethylammonium bromide to 750 mL 0.2 mol / L Ce(SO4)4 solution, stir vigorously until an orange solution is formed, and add 100 mL of 25% ammonia water at 80°C. Then stir at 50°C for 12 h, filter, wash the filter cake with deionized water 6 times (200 mL deionized water each time), and calcine the filter cake in air at 400°C for 4 h and 450°C for 4 h. 21.6 g of m-CeO2 with a specific surface area of ​​496 m 2 / g, average pore diameter of 7.9nm, and pore volume of 0.98mL / g of m-CeO2.

[0044] Preparation of V2O5-MoO3 / m-CeO2 catalyst: Add 0.00413mol of ammonium metavanadate and 0.00352mol of hydrated ammonium heptamolybdate to 30mL of deionized water, and dissolve them by ultrasonication at room temperature for 10min. Add 20g of the prepared m-CeO2, and then ultrasonicate at 80℃ until the water is basically evaporated. Place the impregnated material in a furnace and roast it at 600℃ for 2h to obtain 24.0g of V2O5-MoO3 / m-CeO2 catalyst. According to the feed amount, the active component loading is 20% (relative to the weight of the carrier m-CeO2), where Mo:V=6:1 (molar ratio). Named as catalyst 3#.

[0045] Example 4

[0046] Catalyst 1# catalyzes the oxidation of phthalimide by hydrogen peroxide to synthesize NHPI:

[0047] Add 30g phthalimide (0.2mol), 90g tert-butyl alcohol, and 4.5g 1# catalyst into the reaction bottle. Add 13.6g hydrogen peroxide (0.3mol) with a weight concentration of 75% at 50°C for 2h under sufficient stirring. After the addition is completed, continue to react at 50°C for 6h.

[0048] After the reaction is completed, the catalyst is filtered off and tert-butyl alcohol is recovered under reduced pressure. The by-product water is distilled off to obtain a solid crude product. The crude product is dissolved in 80 g 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 23.1 g of N-hydroxyphthalimide product, with a purity of 99.3% according to high pressure liquid chromatography analysis, and a product NHPI yield of 70.4%. 1 H-NMR (DMSO-d6) δ: 10.82 (s, 1H), 7.84 (s, 4H).

[0049] The HPLC chromatogram of the obtained product NHPI is as follows: Figure 1 As shown, the product NHPI hydrogen spectrum is as follows Figure 2 shown.

[0050] Example 5

[0051] Catalyst 2# catalyzes the oxidation of phthalimide with hydrogen peroxide to synthesize NHPI:

[0052] Add 30g phthalimide (0.2mol), 80g acetonitrile and 3.6g 2# catalyst into the reaction bottle. Add 13.6g hydrogen peroxide (0.28mol) with a weight concentration of 70% at 60°C for 3h under sufficient stirring. After the addition is completed, continue to react at 60°C for 8h.

[0053] After the reaction is completed, the catalyst is filtered off and the acetonitrile is recovered under reduced pressure. The by-product water is evaporated 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, and dried by rotary evaporation at room temperature to obtain 23.9g of N-hydroxyphthalimide product, with a purity of 99.2% according to high pressure liquid chromatography analysis and a product yield of 72.7%. 1 H-NMR (DMSO-d6) δ: 10.82 (s, 1H), 7.84 (s, 4H).

[0054] Example 6

[0055] Catalyst 3# catalyzes the oxidation of phthalimide by hydrogen peroxide to synthesize NHPI:

[0056] Add 30g of phthalimide (0.2mol), 100g of dioxane and 3.0g of catalyst #3 into the reaction bottle. Add 13.6g of 65% hydrogen peroxide (0.26mol) dropwise at 70°C for 4h under sufficient stirring. After the addition is complete, continue to react at 70°C for 5h.

[0057] After the reaction is completed, the catalyst is filtered off, and the dioxane is recovered by vacuum distillation, 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, and dried by rotary evaporation at room temperature to obtain 23.3g of N-hydroxyphthalimide product, with a purity of 99.3% according to high pressure liquid chromatography analysis, and a product yield of 71.0%. 1 H-NMR (DMSO-d6) δ: 10.82 (s, 1H), 7.84 (s, 4H).

[0058] Example 7

[0059] Catalyst 3# catalyzes the oxidation of phthalimide by hydrogen peroxide to synthesize NHPI:

[0060] Add 30g phthalimide (0.2mol), 90g ethylene glycol dimethyl ether, and 2.4g 3# catalyst into the reaction bottle. Under sufficient stirring, add 13.6g hydrogen peroxide (0.24mol) with a weight concentration of 60% at 80°C for 4h. After the addition is completed, continue to react at 80°C for 4h.

[0061] After the reaction is completed, the catalyst is filtered off and ethylene glycol dimethyl ether is recovered under reduced pressure. 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, and dried by rotary evaporation at room temperature to obtain 23.2g of NHPI 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).

[0062] Example 8

[0063] Catalyst 2# catalyzes the oxidation of phthalimide by hydrogen peroxide to synthesize NHPI:

[0064] 30 g of phthalimide (0.2 mol), 80 g of benzonitrile, and 4.5 g of catalyst #2 were added to the reaction flask. Under sufficient stirring, 12.7 g of 75% weight concentration hydrogen peroxide (0.28 mol) was added dropwise at 65° C. for 4 h. After the addition was completed, the reaction was continued at 65° C. for 7 h.

[0065] After the reaction is completed, the catalyst is filtered off, and water and benzonitrile are distilled off under reduced pressure to obtain a solid crude product. The crude product is dissolved in 80 g 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 24.7 g of NHPI product, with a purity of 99.3% according to high pressure liquid chromatography analysis, and a yield of NHPI product of 75.2%. 1 H-NMR (DMSO-d6) δ: 10.82 (s, 1H), 7.84 (s, 4H).

[0066] Comparative Example 1

[0067] N-hydroxyphthalimide was prepared according to the method described in Chinese patent CN1239715 (synthesis method of N-hydroxyphthalimide).

[0068] Dissolve 25.0 g of phthalic anhydride in 100 mL of hydrated organic solvent (containing 50% organic solvent C4H8O2, v / v), then add 13.0 g of hydroxylamine hydrochloride, and react at 85-90°C for 4 hours. After the reaction is completed, evaporate the organic solvent under reduced pressure and dry to obtain 24.7 g of white solid with a yield of 90%.

[0069] 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.

[0070] Comparative Example 2

[0071] N-hydroxyphthalimide was prepared according to the method described in Chinese patent CN105111128A (a method for preparing N-hydroxyphthalimide).

[0072] 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%.

[0073] 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.

[0074] By comparison with Comparative Examples 1 and 2, it can be seen that the technical method of the present invention uses V2O5-MoO3 / m-CeO2 as a catalyst and adopts a 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 during the preparation process, and highly toxic hydroxylamine hydrochloride is not used, and the by-product is H2O, and the production process is green and environmentally friendly.

Claims

1. A method for synthesizing N-hydroxyphthalimide, characterized in that: In an organic solvent, phthalimide reacts with 60-75% hydrogen peroxide under the action of a catalyst, molybdenum-vanadium oxide, to obtain N-hydroxyphthalimide; the catalyst is molybdenum-vanadium oxide supported by mesoporous cerium dioxide, and the weight loading amount of molybdenum-vanadium oxide in the catalyst is 10-20% of the mesoporous cerium dioxide; the average pore diameter of the mesoporous cerium dioxide is 4-8nm, and the average pore volume is 0.55-1.0mL / g; the molar ratio of molybdenum to vanadium in the molybdenum-vanadium oxide is 4-6:

1.

2. The synthesis method according to claim 1, characterized in that The molar ratio of hydrogen peroxide to phthalimide is 1.2-1.5:1.

0.

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

4. The synthesis method according to claim 1, characterized in that The reaction temperature of the synthesis method is 50°C to 80°C.

5. The synthesis method according to claim 1, characterized in that Hydrogen peroxide is slowly added to the organic solvent containing phthalamide.

6. The synthesis method according to claim 1, characterized in that The synthesis method of the catalyst is as follows: (1) adding triethylamine or triethylenetetramine to a Ce(SO4)4 solution and stirring to obtain a yellow solution; (2) heating to 50-80°C, adding aqueous ammonia to the solution obtained in step (1) for reaction; (3) filtering the intermediate product obtained in step (2), and then calcining at 400-500°C for 2-6h to obtain mesoporous cerium dioxide; (4) adding the mesoporous cerium dioxide obtained in step (3) to an aqueous solution of ammonium metavanadate and hydrated ammonium heptamolybdate, evaporating water at 50-80°C to obtain an impregnation; (5) calcining the impregnation at 400-600°C for 2-6h to obtain a catalyst.

7. The synthesis method according to any one of claims 1 to 6, characterized in that: The amount of the catalyst used is 8-15% of the weight of phthalimide.

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