CN113387870A - Synthesis method of N-hydroxyphthalimide - Google Patents
Synthesis method of N-hydroxyphthalimide Download PDFInfo
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- CN113387870A CN113387870A CN202110689059.6A CN202110689059A CN113387870A CN 113387870 A CN113387870 A CN 113387870A CN 202110689059 A CN202110689059 A CN 202110689059A CN 113387870 A CN113387870 A CN 113387870A
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- hydroxyphthalimide
- phthalic anhydride
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
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Abstract
The invention discloses a synthetic method of N-hydroxyphthalimide, which comprises the following steps: the method comprises the steps of taking phthalic anhydride and hydroxylamine hydrochloride as raw materials, carrying out reflux dehydration and dehydrochlorination reaction in a high-boiling point inert solvent, and obtaining the N-hydroxyphthalimide with high yield by simple filtration after the reaction is finished. The molar yield of the invention can reach more than 98 percent, and the product purity can reach more than 99 percent. Compared with the prior art, the invention has the following beneficial effects: the invention uses the high boiling point inert solvent to replace the traditional water or dioxane aqueous solution as the solvent, thereby avoiding a large amount of waste water generated by the reaction, directly applying the reaction solvent without recovery treatment, reducing the production management cost, reducing the pollution discharge, improving the production efficiency, simultaneously improving the conversion rate and realizing the saving of the atom utilization rate.
Description
Technical Field
The invention relates to a synthetic method of N-hydroxyphthalimide.
Background
N-hydroxyphthalimide, the molecular structural formula is:
n-hydroxyphthalimide, also known as N-hydroxymethylphthalimide, is known under the trade name NOP. N-hydroxyphthalimides are important intermediates for amikacin and are also important oxidation catalysts.
The existing synthesis method of N-hydroxyphthalimide is mainly obtained by reacting phthalic anhydride with hydroxylamine hydrochloride. CN1051170A discloses that phthalic anhydride and hydroxylamine hydrochloride react in water to give the product with a yield of 80-85%. In practice, the reaction is carried out in two steps, the first step is to neutralize hydroxylamine hydrochloride with sodium carbonate to obtain free hydroxylamine, and the second step is to ring-close the free hydroxylamine and phthalic anhydride to obtain the product. The method of CN1051170A can generate a large amount of salt-containing wastewater and is seriously polluted. Patent CN1073989C of Guangzhou chemical research of Chinese academy discloses that phthalic anhydride and hydroxylamine hydrochloride react in a composite solvent of dioxane and water, and a product with the purity of 97 percent can be obtained with the yield of 95 percent without adding alkaline substances such as sodium carbonate and the like to free hydroxylamine. The method of CN1073989C has high atom utilization rate, but generates a large amount of water-containing dioxane which needs rectification, recovery and reuse because of azeotropy with water. The process has the defects of high equipment investment, high recovery cost, low recovery utilization rate and the like.
Disclosure of Invention
The invention aims to provide a method for synthesizing N-hydroxyphthalimide, which adopts phthalic anhydride and hydroxylamine hydrochloride as raw materials, and performs reflux dehydration dehydrochlorination reaction in a high-boiling point inert solvent, and the N-hydroxyphthalimide is obtained with high yield by simple filtration after the reaction is finished. The hydrogen hydride removed from the reaction is absorbed to prepare industrial hydrochloric acid, and the filtered filtrate can be used for the next batch of production without any treatment. The process is simple to operate, safe and easy to control, realizes zero emission, and represents a sustainable development direction of clean production.
The invention aims to realize the synthesis method of N-hydroxyphthalimide by the following technical scheme, and the molecular structural formula of the compound is as follows:
the synthesis method takes phthalic anhydride and hydroxylamine hydrochloride as raw materials, reflux dehydration and dehydrochlorination are carried out in a high-boiling point inert solvent, and after the reaction is finished, the N-hydroxyphthalimide is obtained with high yield through simple filtration. The molar yield of the invention can reach more than 98 percent, and the product purity can reach more than 99 percent.
Compared with the prior art, the invention has the following beneficial effects: the invention uses the high boiling point inert solvent to replace the traditional water or dioxane aqueous solution as the solvent, thereby avoiding a large amount of waste water generated by the reaction, directly applying the reaction solvent without recovery treatment, reducing the production management cost, reducing the pollution discharge, improving the production efficiency, simultaneously improving the conversion rate and realizing the saving of the atom utilization rate.
Detailed Description
The invention is further illustrated by the following examples of embodiments.
A synthetic method of N-hydroxyphthalimide is disclosed, the molecular structural formula of the compound is as follows:
the synthesis method takes phthalic anhydride and hydroxylamine hydrochloride as raw materials, and the product can be obtained by reflux reaction in a high-boiling point inert solvent. Further, the reaction temperature is 140 to 250 ℃, and the reaction time is 5 to 12 hours.
Further, the high-boiling point inert solvent is n-butanol, glycerol or o-dichlorobenzene. The mass of the solvent is 5-10 times of that of the phthalic anhydride.
Further, the molar ratio of phthalic anhydride to hydroxylamine hydrochloride is (0.9-1): 1.
The reaction equation is as follows:
considering that after the phthalic anhydride is excessive, unreacted phthalic anhydride is dissolved in the mother liquor, and the product is unqualified due to the long-term application of the mother liquor. The invention can be separated out along with the product, thereby causing material waste. The invention selects the excess of hydroxylamine hydrochloride, so that the excess hydroxylamine hydrochloride can be separated out along with the product. Finally, the filter cake is simply washed by water to remove the excessive hydroxylamine hydrochloride.
During the specific operation, firstly, measured phthalic anhydride, hydroxylamine hydrochloride and a solvent are put into a reactor, stirred and heated to reflux, the temperature is kept for a period of time for reaction, the temperature is cooled to room temperature, discharging and filtering are carried out, the next batch of materials are used for the filtrate, and a filter cake is washed by water and dried to obtain a finished product.
Example 1
50g (0.34mol) of phthalic anhydride, 25g (0.36mol) of hydroxylamine hydrochloride and 250g of n-butanol were placed in a 1000ml four-necked flask equipped with a mechanical stirrer, a thermometer, a reflux condenser, a tail gas absorption column and an electric jacket, and the heating was started with the stirring started.
When the temperature rises to 123 ℃, the lower end of the reflux condenser is provided with liquid drops for refluxing. Starting the timing and heat preservation. The reaction was incubated for 12 hours. And cooling to room temperature. Filtration and washing of the filter cake with water followed by drying gave 19g of a pale yellow powder. The content of liquid chromatography was 97.11%, and the molar yield was 34.28% based on phthalic anhydride.
Example 2
50g (0.34mol) of phthalic anhydride, 25g (0.36mol) of hydroxylamine hydrochloride and 250g of glycerol were placed in a 1000ml four-necked flask equipped with a mechanical stirrer, a thermometer, a reflux condenser, a tail gas absorption column and an electric jacket, and heating was started with stirring.
When the temperature rises to 200 ℃, the temperature is kept by timing. The reaction was incubated for 12 hours. And cooling to room temperature. Filtration and washing of the filter cake with water followed by drying gave 54.5g of a pale yellow powder. The content of liquid chromatography is 99.15%, calculated by phthalic anhydride, the molar yield is 98.34%.
Example 3
In a 1000ml four-necked flask equipped with a mechanical stirrer, a thermometer, a reflux condenser, a tail gas absorption column and an electric jacket, 50g (0.34mol) of phthalic anhydride, 25g (0.36mol) of hydroxylamine hydrochloride and 250g of o-dichlorobenzene were charged, and the heating was started with the stirring turned on.
When the temperature rises to 182 ℃, the lower end of the reflux condenser has liquid drops to reflux. Starting the timing and heat preservation. The reaction was incubated for 12 hours. And cooling to room temperature. Filtration and washing of the filter cake with water followed by drying gave 38.3g of a pale yellow powder. The liquid chromatography content was 98.07% with a molar yield of 69.11% based on phthalic anhydride.
Example 4
Adding 140kg (950mol) of phthalic anhydride, 69.5kg (1000mol) of hydroxylamine hydrochloride and 980kg of glycerol into a 3000L enamel reaction kettle which is provided with a mechanical stirring device, a thermometer, a 25 square graphite reflux condenser and a tail gas absorption tower, starting stirring, and introducing high-temperature heat conduction oil into a jacket for heating.
When the temperature rises to 200 ℃, the reaction is kept for 10 hours and then cooled to room temperature. Discharging the materials into a centrifuge for centrifugation. The centrifugal filter cake is washed by tap water for 5 minutes, the materials are dried by double-cone rotation and vacuum, and 151kg is obtained by discharging and weighing. The liquid chromatography content was 99.69%, calculated as phthalimide, in a molar yield of 97.51%.
Claims (4)
1. A synthetic method of N-hydroxyphthalimide is disclosed, the molecular structural formula of the compound is as follows:
the method is characterized in that phthalic anhydride and hydroxylamine hydrochloride are used as raw materials, and a product can be obtained by reflux reaction in a high-boiling point inert solvent;
the reaction equation of the synthesis method is as follows:
2. the method for synthesizing N-hydroxyphthalimide according to claim 1, wherein the inert solvent with high boiling point is N-butanol, glycerol or o-dichlorobenzene. The mass of the solvent is 5-10 times of that of the phthalic anhydride.
3. The method for synthesizing N-hydroxyphthalimide according to claim 1, wherein the molar ratio of phthalic anhydride to hydroxylamine hydrochloride is (0.9-1): 1.
4. The method for synthesizing N-hydroxyphthalimide according to claim 1, wherein the reaction temperature is 140 to 250 ℃ and the reaction time is 5 to 12 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110689059.6A CN113387870A (en) | 2021-06-22 | 2021-06-22 | Synthesis method of N-hydroxyphthalimide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110689059.6A CN113387870A (en) | 2021-06-22 | 2021-06-22 | Synthesis method of N-hydroxyphthalimide |
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| CN113387870A true CN113387870A (en) | 2021-09-14 |
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| CN202110689059.6A Pending CN113387870A (en) | 2021-06-22 | 2021-06-22 | Synthesis method of N-hydroxyphthalimide |
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| CN (1) | CN113387870A (en) |
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2021
- 2021-06-22 CN CN202110689059.6A patent/CN113387870A/en active Pending
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Inventor after: Zou Congwei Inventor after: Zhang Yan Inventor after: Li Fu Inventor after: Li Ming Inventor after: Zhang Rongcui Inventor after: Niu Wei Inventor before: Zhang Yan Inventor before: Zou Congwei Inventor before: Li Fu Inventor before: Li Ming Inventor before: Zhang Rongcui Inventor before: Niu Wei |
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