CN112457256A - Preparation method of DL-p-hydroxyphenylhydantoin - Google Patents
Preparation method of DL-p-hydroxyphenylhydantoin Download PDFInfo
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- CN112457256A CN112457256A CN202011309944.9A CN202011309944A CN112457256A CN 112457256 A CN112457256 A CN 112457256A CN 202011309944 A CN202011309944 A CN 202011309944A CN 112457256 A CN112457256 A CN 112457256A
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- hydroxyphenylhydantoin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
- C07D233/78—Radicals substituted by oxygen atoms
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Abstract
The invention discloses a preparation method of DL-p-hydroxyphenylhydantoin. Adding phenol, sulfuric acid with the mass concentration of 98% and water into a reaction kettle, catalyzing phenol para-activity by using a sulfuric acid aqueous solution with a certain concentration, heating, adding a catalyst with the total molar weight of 1/3, adding urea, preserving heat, and adding a certain amount of water; slowly dropwise adding a glyoxylic acid aqueous solution with the total molar weight of 1/3, after dropwise adding, adding a catalyst with the residual total molar weight of 2/3, after stirring to generate a turbid phenomenon, increasing the reaction temperature, dropwise adding a glyoxylic acid aqueous solution with the residual total molar weight of 2/3, after dropwise adding, keeping the temperature, cooling, keeping the temperature, and performing centrifugal suction filtration to keep a solid; and (5) overflowing hot water on the surface of the solid material for washing until the pH is neutral, and drying. The method improves the yield and purity of the product, reduces the content of phenol in the mother liquor, reduces the amount of wastewater, relieves the pressure of environmental protection, effectively inhibits the generation of maximum single impurities, and improves the yield and quality of the product.
Description
Technical Field
The invention relates to the technical field of DL-p-hydroxyphenylhydantoin, in particular to a preparation method of DL-p-hydroxyphenylhydantoin.
Background
At present, most of domestic DL-p-hydroxyphenylhydantoin production processes adopt a hydrochloric acid method synthesis process route, and the production processes have the following defects: 1. high-temperature reaction is needed in the production process, a large amount of harmful HCL gas is generated, the production equipment is corroded, and the maintenance cost is high. The environmental protection pressure is large due to the poor operating environment of workers. 2. Hydrogen chloride gas is easy to volatilize, so that the concentration of hydrochloric acid in reaction liquid is unstable, and the fluctuation of the content and the yield of the product is large. 3. The wastewater amount is large, and the subsequent wastewater treatment cost is high.
The patent reports that the p-hydroxy-phenyl-hydantoin can be synthesized by using a dilute sulfuric acid process instead of a hydrochloric acid process, the problems of low content, unstable yield and large wastewater amount are not solved, and the problems of prolonged process route, complex operation and the like can be caused because the market standard can be met through subsequent water washing pulping or organic solvent refining.
The concentration of the sulfuric acid is improved, the use amount of the sulfuric acid is reduced, the subsequent waste water amount is reduced, or the forward reaction is promoted by adding a catalyst, and the reduction of the generation of side reactions is the current domestic research direction. Many patents also mention that the reaction yield is improved by adding catalysts, such as solid acid, phase transfer catalyst, etc., which are only embodied in dilute sulfuric acid or dilute hydrochloric acid systems, and the problem of large amount of waste water is not solved fundamentally.
Disclosure of Invention
In order to solve the problems in the traditional production, the invention provides a preparation method of DL-p-hydroxyphenylhydantoin.
The invention provides the following technical scheme:
step 1, adding phenol, sulfuric acid with the mass concentration of 98% and a small amount of water into a reaction kettle according to the molar ratio, carrying out catalytic reaction for 1h at 45-50 ℃, taking a sulfuric acid aqueous solution with a certain concentration as a catalyst, slowly raising the temperature to control the reaction temperature to be 55-65 ℃, adding the catalyst with the total molar amount of 1/3, adding urea, preserving heat for 1h, and supplementing a certain amount of water after the heat preservation is finished;
step 2, slowly dropwise adding a glyoxylic acid aqueous solution with the total molar weight of 1/3 into the reaction liquid obtained in the step 1;
step 3, adding the catalyst with the total molar amount of 2/3 in the rest, stirring for 30min after the materials start to generate a turbid phenomenon, increasing the reaction temperature, controlling the temperature in the reaction kettle to be not less than 85 ℃, continuously and slowly adding the glyoxylic acid aqueous solution with the total molar amount of 2/3 in the rest, keeping the temperature for 1-2h after the dropwise addition is finished, cooling to 50 ℃, keeping the temperature for 30min, performing centrifugal filtration, and keeping the solid;
and 4, after centrifugal filtration is finished, overflowing prepared hot water with the temperature of not lower than 85 ℃ over the surface of the solid material for washing until the pH is neutral, and drying to obtain a finished product.
In the step 1, the molar ratio of the phenol to the urea to the sulfuric acid to the catalyst to the glyoxylic acid is (0.8-1.0) to (1.8-2.0) to (0.5-0.6) to (0.01-0.015) to (0.8-1.0).
In the step 1, the mass concentration of the sulfuric acid aqueous solution is 68-72% when catalyzing phenol.
In the step 1, after the urea is added, the water is added in an amount which is 0.15 to 0.2 times the weight of the 98 percent concentrated sulfuric acid.
In the step 2, the dropping time of the glyoxylic acid aqueous solution is controlled to be 2-3 h.
In the step 3, the dropping time of the glyoxylic acid aqueous solution is controlled to be 5-7 h.
The catalyst is one of dodecyl trimethyl ammonium bromide and hexadecyl trimethyl ammonium bromide.
The mass concentration of the glyoxylic acid aqueous solution in the steps 2 and 3 is 40-50%.
The standard of the finished product obtained in the step 4 is specifically as follows: drying at 80-90 deg.C until the water content is not higher than 0.5% and the content is not lower than 99.0%.
The invention has the beneficial effects that:
the invention improves the product yield and content, reduces the phenol content in the mother liquor, reduces the waste water amount and lightens the environmental protection pressure.
The invention synthesizes the p-hydroxy phenyl hydantoin by step catalysis through step temperature rise and step catalyst and glyoxylic acid, effectively inhibits the generation of maximum single impurity and improves the yield and content of the product.
The p-hydroxy phenyl hydantoin synthesized by the method has pure white color, the yield is 70-75% (based on glyoxylic acid), and the content is more than 99.0%.
Detailed Description
The invention is further described with reference to specific embodiments.
The embodiment of the invention is concretely as follows:
the first embodiment is as follows: adding 10 g of water into a 500ml three-necked bottle, dropwise adding 25 g of concentrated sulfuric acid, controlling the internal temperature to be 45 ℃, adding 47 g of phenol, stirring for 1h, heating to 55 ℃, adding 0.6 g of dodecyltrimethylammonium bromide, adding 60 g of urea, keeping the temperature for 1h, supplementing 4 g of water, controlling the internal temperature to be 55-60 ℃, dropwise adding 31 g of glyoxylic acid (mass fraction of 40%) within the internal temperature, dropwise adding for 2h, ending dropwise adding, adding 1.2 g of dodecyltrimethylammonium bromide, stirring for 20min, starting turbidity, keeping the temperature for 30min, heating to 85 ℃, dropwise adding 62 g of the remaining glyoxylic acid (mass fraction of 40%) within the temperature of 85 ℃, keeping the temperature for 2h after dropwise adding, cooling to 50 ℃, keeping the temperature for half an hour, centrifuging, extracting a solid material, washing to be neutral by using 85-degree hot water, drying the material at 85 ℃, and obtaining 70.3 g, 99.25% and 0.32% of a maximum single.
Example two: adding 10 g of water into a 500ml three-necked bottle, dropwise adding 25 g of concentrated sulfuric acid, controlling the internal temperature to be 45 ℃, adding 47 g of phenol, stirring for 1h, heating to 55 ℃, adding 0.7 g of hexadecyl trimethyl ammonium bromide, adding 60 g of urea, preserving heat for 1h, supplementing 4 g of water, controlling the internal temperature to be 55-60 ℃, dropwise adding 31 g of glyoxylic acid (mass fraction is 40%) in, dropwise adding for 2h, finishing dropwise adding, adding 1.4 g of hexadecyl trimethyl ammonium bromide, stirring for 20min, starting turbidity, preserving heat for 30min, heating to 85 ℃, dropwise adding 62 g of residual glyoxylic acid (mass fraction is 40%), preserving heat for 6h, cooling to 50 ℃, preserving heat for half an hour, centrifuging, extracting a solid material, washing to be neutral by using 85 ℃ hot water, drying the material at 85 ℃ to obtain 70.6 g of a product, the purity is 99.31%, and the maximum single impurity content is 0.30%.
Comparative example one: adding 10 g of water into a 500ml three-necked bottle, dropwise adding 25 g of concentrated sulfuric acid, controlling the internal temperature to be 45 ℃, adding 47 g of phenol, stirring for 1h, heating to 55 ℃, adding 60 g of urea, keeping the temperature for 1h, supplementing 4 g of water, controlling the internal temperature to be 55-60 ℃, dropwise adding 31 g of glyoxylic acid (with the mass fraction of 40%) while controlling the internal temperature to be 2h, finishing dropwise adding, stirring for 60min, starting turbidity, keeping the temperature for 30min, heating to 85 ℃, dropwise adding 62 g of residual glyoxylic acid (with the mass fraction of 40%) while keeping the temperature for 6h, keeping the temperature for 85 ℃ after dropwise adding is finished, cooling to 50 ℃, keeping the temperature for half an hour, centrifuging, extracting a solid material, washing to be neutral by using 85 ℃ hot water, drying the material at 85 ℃ to obtain 58.44 g of a product, the purity of 96..
Comparative example two: adding 10 g of water into a 500ml three-necked bottle, dropwise adding 25 g of concentrated sulfuric acid, controlling the internal temperature to be 45 ℃, adding 47 g of phenol, heating to 55 ℃, adding 60 g of urea, preserving heat for 1h, supplementing 4 g of water, controlling the internal temperature to be 55-60 ℃, dropwise adding 31 g of glyoxylic acid (mass fraction of 40%) within 2h, finishing dropwise adding, stirring for 60min, starting turbidity, preserving heat for 30min, heating to 85 ℃, dropwise adding 62 g of residual glyoxylic acid (mass fraction of 40%) within 6h, preserving heat for 2h at 85 ℃ after dropwise adding, cooling to 50 ℃, preserving heat for half an hour, centrifuging, extracting a solid material, washing to be neutral by using 85-DEG hot water, drying the material at 85 ℃ to obtain 63.23 g of a product, the purity is 95.55%, and the maximum single impurity content is 4.31%.
Therefore, the method improves the product yield and purity, reduces the content of phenol in the mother liquor, reduces the amount of wastewater, relieves the environmental protection pressure, effectively inhibits the generation of maximum single impurities, and improves the product yield and quality.
Claims (9)
1. A preparation method of DL-p-hydroxyphenylhydantoin is characterized in that: the method comprises the following steps:
step 1, adding phenol, sulfuric acid with the mass concentration of 98% and water into a reaction kettle according to the molar ratio, carrying out catalytic reaction for 1h at 45-50 ℃, raising the temperature to control the reaction temperature to be 55-65 ℃, adding a catalyst with the total molar amount of 1/3, adding urea, preserving heat for 1h, and supplementing a certain amount of water after the heat preservation is finished;
step 2, slowly dropwise adding a glyoxylic acid aqueous solution with the total molar weight of 1/3 into the reaction liquid obtained in the step 1;
step 3, adding the catalyst with the total molar amount of 2/3 in the rest, stirring for 30min after the materials start to generate a turbid phenomenon, increasing the reaction temperature, controlling the temperature in the reaction kettle to be not less than 85 ℃, continuously and slowly adding the glyoxylic acid aqueous solution with the total molar amount of 2/3 in the rest, keeping the temperature for 1-2h after the dropwise addition is finished, cooling to 50 ℃, keeping the temperature for 30min, performing centrifugal filtration, and keeping the solid;
and 4, after centrifugal filtration is finished, overflowing prepared hot water with the temperature of not lower than 85 ℃ over the surface of the solid material for washing until the pH is neutral, and drying to obtain a finished product.
2. The method for preparing DL-p-hydroxyphenylhydantoin according to claim 1, wherein the method comprises the following steps:
in the step 1, the molar ratio of the phenol to the urea to the sulfuric acid to the catalyst to the glyoxylic acid is (0.8-1.0) to (1.8-2.0) to (0.5-0.6) to (0.01-0.015) to (0.8-1.0).
3. The method for preparing DL-p-hydroxyphenylhydantoin according to claim 1, wherein the method comprises the following steps:
in the step 1, the mass concentration of the sulfuric acid aqueous solution is 68-72%.
4. The method for preparing DL-p-hydroxyphenylhydantoin according to claim 1, wherein the method comprises the following steps:
in the step 1, the water is supplemented by 0.15-0.2 times of the weight of 98% concentrated sulfuric acid.
5. The method for preparing DL-p-hydroxyphenylhydantoin according to claim 1, wherein the method comprises the following steps:
in the step 2, the dropping time of the glyoxylic acid aqueous solution is controlled to be 2-3 h.
6. The method for preparing DL-p-hydroxyphenylhydantoin according to claim 1, wherein the method comprises the following steps:
in the step 3, the dropping time of the glyoxylic acid aqueous solution is controlled to be 5-7 h.
7. The method for preparing DL-p-hydroxyphenylhydantoin according to claim 1, wherein the method comprises the following steps:
the catalyst is one of dodecyl trimethyl ammonium bromide and hexadecyl trimethyl ammonium bromide.
8. The method for preparing DL-p-hydroxyphenylhydantoin according to claim 1, wherein the method comprises the following steps:
the mass concentration of the glyoxylic acid aqueous solution in the steps 2 and 3 is 40-50%.
9. The method for preparing DL-p-hydroxyphenylhydantoin according to claim 1, wherein the method comprises the following steps:
the standard of the finished product obtained in the step 4 is specifically as follows: drying at 80-90 deg.C until the water content is not higher than 0.5% and the content is not lower than 99.0%.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0001319A1 (en) * | 1977-08-18 | 1979-04-04 | Beecham Group Plc | Process for the preparation of hydroxyphenyl hydantoin and of hydroxyphenyl glycine, and compounds thus obtained |
| CN107973753A (en) * | 2017-11-27 | 2018-05-01 | 天津市职业大学 | A kind of method of phase-transfer Wittig reaction 4-Hydroxyphenyl hydantoin |
| CN111807877A (en) * | 2020-07-09 | 2020-10-23 | 定陶三化药业有限公司 | DL-p-hydroxyphenylhydantoin and production process of urea sulfate/ammonium sulfate thereof |
-
2020
- 2020-11-20 CN CN202011309944.9A patent/CN112457256B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0001319A1 (en) * | 1977-08-18 | 1979-04-04 | Beecham Group Plc | Process for the preparation of hydroxyphenyl hydantoin and of hydroxyphenyl glycine, and compounds thus obtained |
| CN107973753A (en) * | 2017-11-27 | 2018-05-01 | 天津市职业大学 | A kind of method of phase-transfer Wittig reaction 4-Hydroxyphenyl hydantoin |
| CN111807877A (en) * | 2020-07-09 | 2020-10-23 | 定陶三化药业有限公司 | DL-p-hydroxyphenylhydantoin and production process of urea sulfate/ammonium sulfate thereof |
Non-Patent Citations (1)
| Title |
|---|
| 陈红飙等: "D/ L-对羟苯海因的"一锅法"合成", 《化学世界》 * |
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