CN113387843B - Method for synthesizing O-methyl isourea hydrogen sulfate - Google Patents
Method for synthesizing O-methyl isourea hydrogen sulfate Download PDFInfo
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- CN113387843B CN113387843B CN202110405720.6A CN202110405720A CN113387843B CN 113387843 B CN113387843 B CN 113387843B CN 202110405720 A CN202110405720 A CN 202110405720A CN 113387843 B CN113387843 B CN 113387843B
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Abstract
The invention discloses a method for synthesizing O-methyl isourea hydrogen sulfate, belonging to the technical field of organic synthesis. The methylation reaction is carried out in the ultrasonic reaction kettle, and the ultrasonic generator intermittently works according to the specific frequency, so that the reaction time is shortened, the reaction temperature is reduced, and the product yield is improved. The methylation reaction related to the patent is carried out by adopting an ultrasonic reaction kettle, and is a new green synthesis technology with safety and environmental protection.
Description
Technical Field
The invention relates to a method for synthesizing O-methylisourea hydrogen sulfate, belonging to the technical field of organic synthesis.
Background
The O-methylisourea bisulphate belongs to pesticide intermediates, and is mainly used as an intermediate for preparing clothianidin (clothianidin) and dinotefuran (dinotefuran) with insecticidal activity.
One synthetic route for O-methylisourea hydrogen sulfate is: dimethyl sulfate and urea are used as reaction raw materials, the reaction is carried out for 50 minutes at 100 ℃ to generate O-methyl isourea sulfate, after the reaction is stopped, the O-methyl isourea sulfate is pressed into a salt forming kettle, concentrated sulfuric acid and water are sequentially added for hydrolysis, and methanol is used for recrystallization. The yield of the two-step reaction is 55% and the yield of the crystal is 50%. The method has high temperature in the reaction process, and the dimethyl sulfate belongs to a highly toxic product, so that great potential safety hazard is easily caused by careless operation.
Urea and dimethyl sulfate are difficult to react at normal temperature, once the temperature is raised to react, the temperature of a reaction system is rapidly raised, potential safety hazards are caused, and byproducts are easily generated at high temperature, so that the yield of O-methyl isourea methyl sulfate is reduced.
Disclosure of Invention
[ problem ] to
The invention aims to solve the technical problems that the existing method for preparing O-methyl isourea hydrogen sulfate has high temperature and long reaction time, so that the yield is low, the dimethyl sulfate methylation process has potential safety hazards and the like.
[ solution ]
The invention provides a method for synthesizing O-methylisourea hydrogen sulfate, which comprises the following steps: step 1, dimethyl sulfate, urea and an inorganic base catalyst react under the ultrasonic condition to obtain reaction liquid containing O-methylisourea methyl sulfate; step 2, hydrolyzing the reaction solution containing O-methylisourea methyl sulfate by acid under the ultrasonic condition to prepare O-methylisourea hydrogen sulfate,
preferably, the inorganic base catalyst is any one or more of sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide or potassium bicarbonate.
Preferably, the acid is a 10-49% by mass aqueous solution of sulfuric acid.
Preferably, the volume ratio of the O-methylisourea methyl sulfate-containing reaction liquid to the acid is 1: (1-3).
Preferably, the molar ratio of dimethyl sulfate, urea and catalyst is (1.0-4.0): 1: (0.01-0.5).
Preferably, in step 1, the reaction temperature is 40 ℃ to 80 ℃, more preferably, the reaction temperature is 50 ℃ to 55 ℃.
Preferably, the ultrasonic wave conditions are that the ultrasonic wave power is 500w-550w and the ultrasonic wave frequency is 20kHz-25kHz.
Preferably, step 1 further comprises the following steps: dimethyl sulfate, urea and a catalyst are added into a reaction vessel with an ultrasonic device, under the protection of inert gas and under the condition of intermittent ultrasonic reaction, the reaction temperature is controlled to be 50-55 ℃, the intermittent ultrasonic reaction condition is that the reaction time is m minutes, the ultrasonic device pauses for q minutes every p minutes when the ultrasonic device works within 0-n minutes after the reaction starts, the ultrasonic device pauses for u minutes and v minutes when the ultrasonic device works within n-m minutes, m is more than or equal to 20 and less than or equal to 30, m/2 is more than or equal to 0 and less than or equal to 1, q is more than 0 and less than or equal to 1, u is more than 0 and less than or equal to 2, and v is more than or equal to 0 and less than or equal to 1.
More preferably, n is more than 5 m/2, p is more than 0.5 p 1, u is more than 0.5 u 2.
Preferably, the reaction vessel comprises: a reaction cavity is formed in the kettle body; the ultrasonic generator is arranged at the bottom of the kettle body and is used for emitting ultrasonic waves into the reaction cavity during reaction; the charging pipeline is provided with a charging valve, is arranged on the upper side of the kettle body and is communicated with the reaction cavity; the discharging channel is provided with a discharging valve, is arranged at the lower side of the kettle body and is communicated with the reaction cavity; the exhaust pipeline is arranged at the top of the kettle body and is communicated with the reaction cavity; and a circulation channel disposed in the reaction cavity.
More preferably, the ultrasonic generator has an ultrasonic horn for adjusting the operating frequency of the ultrasonic generator.
More preferably, the volume of the reaction cavity is 1L to 100L.
Preferably, step 2 further comprises the following steps: adding acid into O-methyl isourea methyl sulfate, hydrolyzing at 20-25 ℃, cooling to 0-5 ℃ after the reaction is finished, standing for 8-10 h, filtering to obtain a crude O-methyl isourea hydrogen sulfate product, and recrystallizing with a recrystallization agent to obtain the O-methyl isourea hydrogen sulfate. The ultrasonic reaction in the step 2 adopts intermittent ultrasonic reaction conditions, the reaction time is m minutes, the ultrasonic device pauses for q minutes every p minutes when working within 0-n minutes after the reaction starts, the ultrasonic device pauses for v minutes every u minutes when working within n-m minutes, m is more than or equal to 20 and less than or equal to 30, m/2 is more than or equal to n, p is more than or equal to 1 and more than 0 and less than or equal to 1, u is more than 0 and less than or equal to 2, and v is more than 0 and less than or equal to 1. More preferably, n is more than 5 m/2, p is more than 0.5 p 1, u is more than 0.5 u 2.
Preferably, the recrystallization agent is any one or more of methanol, ethanol, n-propanol, isopropanol, n-butanol, t-butanol, tetrahydrofuran, acetonitrile, t-butyl methyl ether, or acetone.
More preferably, the recrystallization agent includes at least one alcoholic solvent and one non-alcoholic solvent.
More preferably, the recrystallization agent consists of an alcoholic solvent and t-butyl methyl ether.
More preferably, the recrystallization agent is ethanol or ethanol and tert-butyl methyl ether in a volume ratio of (5-15): 1.
[ advantageous effects ]
According to the method for synthesizing the O-methylisourea hydrogen sulfate, urea and dimethyl sulfate are used as raw materials, the reaction is carried out under the ultrasonic condition, and the ultrasonic cavitation phenomenon is utilized, so that cavitation bubbles collapse to generate local high-temperature, high-pressure and strong shock waves and jet flow, and the reaction is promoted, therefore, the method not only can ensure that the total yield of the O-methylisourea methyl sulfate reaches more than 70%, but also can ensure that the product purity reaches more than 96%, and can directly participate in the subsequent reaction without further treatment.
Drawings
FIG. 1 is a schematic structural view of an ultrasonic reactor used in the examples of the present application;
FIG. 2 is a high performance liquid chromatogram of O-methylisourea hydrogen sulfate obtained in example 10 of the present application;
FIG. 3 is a high performance liquid chromatogram of O-methylisourea hydrogen sulfate obtained in example 11 of the present application.
Detailed Description
In order to make the technical means, the creation features, the achievement purposes and the effects of the invention easy to understand, the invention is specifically described below by combining the embodiment and the attached drawings.
In the following examples, the purity of O-methylisourea hydrogen sulfate was determined by HPLC analysis as follows:
the instrument comprises the following steps: agilent 1100, chromatography column: BDS C18.6 x 250mm,5 μm; mobile phase A: water, mobile phase B: methanol (HPLC grade), flow rate: 1.0mL/min, wavelength: 270nm (254 nm as auxiliary), column temperature: 30 ℃, sample introduction: 10 mu L of the solution; elution time: and (3) 30min. Solvent and diluent: 1:9, preparing a methanol aqueous solution, a sample and a reference substance: precisely weighing a proper amount of the test sample or the reference sample, wherein the concentration of the prepared solution is 0.2mg/mL. The gradient elution procedure is shown in table 1:
TABLE 1 gradient elution schedule
| Time (min) | A(％) | B(％) |
| 0 | 95 | 5 |
| 5 | 90 | 10 |
| 10 | 85 | 15 |
| 15 | 80 | 20 |
| 20 | 10 | 90 |
| 25 | 95 | 5 |
| 30 | 95 | 5 |
The ultrasonic reactor used in the following examples is constructed as shown in FIG. 1.
As shown in fig. 1, an ultrasonic reactor 100 used in the following examples includes: the device comprises a kettle body 10, an ultrasonic generator 20, a feeding pipeline 30, a discharging pipeline 40, an exhaust pipeline 50, a circulating pipeline 60, a stirring device (not shown in the figure) and a temperature control device (not shown in the figure).
The kettle body 10 is cylindrical, and a cylindrical reaction cavity for containing reaction liquid is arranged in the kettle body, and the reaction cavity can be communicated with the outside through a feeding pipeline 30, a discharging pipeline 40, an exhaust pipeline 50 and a circulating pipeline 60. Scales are arranged on the inner wall of the kettle body 10, so that the volume of the materials in the reaction cavity can be conveniently judged.
The ultrasonic generator 20 is installed at the bottom of the kettle 10, is located outside the reaction cavity, and is used for generating ultrasonic waves to act on a reaction system located in the reaction cavity. The ultrasonic generator 20 used in the embodiments described below also has an ultrasonic horn for adjusting the power of the ultrasonic generator 20.
The charging conduit 30 sets up the upside at the cauldron body 10, is linked together with the reaction cavity, is provided with the charging valve on the charging conduit 30, and this charging valve is used for controlling the reaction cavity and passes through charging conduit 30 and external connected state, when needs are to the interpolation material in the reaction cavity, thereby makes the reaction cavity pass through charging conduit 30 and external intercommunication through the state of adjusting the charging valve to make the material pass through during charging conduit 30 gets into the reaction cavity. In the following examples, the filling valve is a ball valve.
The discharge pipeline 40 sets up the downside at the cauldron body 10, is linked together with the reaction cavity, is provided with the bleeder valve on the discharge pipeline 40, and this bleeder valve is used for controlling the reaction cavity and passes through discharge pipeline 40 and external communicating state, when the material is derived from the reaction cavity to needs, thereby makes the reaction cavity pass through charging pipeline 30 and external intercommunication through the state of adjusting the charging valve to make the material flow out through discharge pipeline 40 in following the reaction cavity. In the embodiments described below, the discharge valve is a ball valve.
The exhaust pipeline 50 is arranged at the top of the kettle body, is communicated with the reaction cavity and is used for conveniently replacing gas in the reaction cavity.
The circulating pipeline 60 is circumferentially arranged on the inner wall of the kettle body 10 and is used for introducing condensed water into the circulating pipeline 60 when the circulating condensation is needed.
The stirring device is arranged in the reaction cavity and used for stirring the materials in the reaction cavity.
The temperature control device is used for reacting the temperature of the materials in the cavity. The temperature control device in the embodiment can be directly adjusted at the temperature of-20 ℃ to 150 ℃.
Example 1
The method for synthesizing O-methylisourea hydrogen sulfate provided by the embodiment comprises the following steps:
step 1, adding 1 part by mole of dimethyl sulfate into an ultrasonic reaction kettle, adding 1 part by mole of urea and 0.03 part by mole of sodium carbonate into the ultrasonic reaction kettle, then sequentially adding 1 part by mole of urea and 0.03 part by mole of sodium carbonate, introducing nitrogen for protection, starting an ultrasonic generator, controlling the power of the ultrasonic generator to be 550W and the frequency to be 25kHz, controlling the temperature in the reaction kettle to be 50-55 ℃, controlling the total reaction time to be 27min, recording the time when the temperature in the reaction kettle rises from room temperature to 50-55 ℃ as 0 th minute, intermittently operating the ultrasonic generator in the whole reaction time process, pausing for 1min during the 0-14 min, operating the ultrasonic generator for 1min, pausing for 1min from the 15-27 min, pausing for 2min during operating the ultrasonic generator for 2min, and reacting to obtain a reaction liquid containing O-methylisourea methyl sulfate, wherein the reaction liquid is a thick liquid;
step 2, determining the volume of the reaction liquid containing O-methylisourea methyl sulfate, adding 10% of dilute sulfuric acid into a reaction cavity through a feeding channel, wherein the volume ratio of the added dilute sulfuric acid to the reaction liquid containing O-methylisourea methyl sulfate is 3.
Example 2
The method for synthesizing O-methylisourea hydrogen sulfate provided by the embodiment comprises the following steps:
step 1, adding 2 parts by mole of dimethyl sulfate into an ultrasonic reaction kettle, adding urea and sodium carbonate into the ultrasonic reaction kettle, sequentially adding 1 part by mole of urea and 0.03 part by mole of sodium carbonate, introducing nitrogen for protection, starting an ultrasonic generator, controlling the power of the ultrasonic generator to be 550W and the frequency to be 25kHz, controlling the temperature in the reaction kettle to be 50-55 ℃, controlling the total reaction time to be 27min, recording the time when the temperature in the reaction kettle rises from room temperature to 50-55 ℃ as 0 th minute, intermittently operating the ultrasonic generator in the whole reaction time process, pausing for 1min during the 0-14 min of the operation of the ultrasonic generator, pausing for 1min from the 15-27 min of the operation of the ultrasonic generator for 2min, and reacting to obtain a reaction liquid containing O-methylisourea methyl sulfate, wherein the reaction liquid is a thick liquid;
step 2, determining the volume of the reaction liquid containing O-methylisourea methyl sulfate, adding 10% dilute sulfuric acid by mass fraction into a reaction cavity through a feeding channel, wherein the volume ratio of the added dilute sulfuric acid to the reaction liquid containing O-methylisourea methyl sulfate is 3.
Example 3
The method for synthesizing O-methylisourea hydrogen sulfate provided by the embodiment comprises the following steps:
step 1, adding 3 parts by mole of dimethyl sulfate into an ultrasonic reaction kettle, adding 1 part by mole of urea and 0.03 part by mole of sodium carbonate into the ultrasonic reaction kettle, introducing nitrogen for protection, starting an ultrasonic generator, controlling the power of the ultrasonic generator to be 550W and the frequency to be 25kHz, controlling the temperature in the reaction kettle to be 50-55 ℃, controlling the total reaction time to be 27min, recording the time when the temperature in the reaction kettle rises from room temperature to 50-55 ℃ as 0 th minute, intermittently operating the ultrasonic generator in the whole reaction time process, pausing for 1min when the ultrasonic generator operates for 0-14 min, pausing for 1min when the ultrasonic generator operates for 2min when the temperature in the reaction kettle rises from room temperature to 15-27 min, and reacting to obtain a reaction liquid containing O-methylisourea methyl sulfate, wherein the reaction liquid is a thick liquid;
step 2, determining the volume of the reaction liquid containing O-methylisourea methyl sulfate, adding 10% dilute sulfuric acid by mass fraction into a reaction cavity through a feeding channel, wherein the volume ratio of the added dilute sulfuric acid to the reaction liquid containing O-methylisourea methyl sulfate is 3.
Example 4
The method for synthesizing O-methylisourea hydrogen sulfate provided by the embodiment comprises the following steps:
step 1, adding 3 parts by mole of dimethyl sulfate into an ultrasonic reaction kettle, adding 1 part by mole of urea and 0.15 part by mole of sodium carbonate into the ultrasonic reaction kettle, introducing nitrogen for protection, starting an ultrasonic generator, controlling the power of the ultrasonic generator to be 550W and the frequency to be 25kHz, controlling the temperature in the reaction kettle to be 50-55 ℃, controlling the total reaction time to be 27min, recording the time when the temperature in the reaction kettle rises from room temperature to 50-55 ℃ as 0 th minute, intermittently operating the ultrasonic generator in the whole reaction time process, pausing for 1min when the ultrasonic generator operates for 0-14 min, pausing for 1min when the ultrasonic generator operates for 2min when the temperature in the reaction kettle rises from room temperature to 15-27 min, and reacting to obtain a reaction liquid containing O-methylisourea methyl sulfate, wherein the reaction liquid is a thick liquid;
step 2, determining the volume of the reaction liquid containing O-methylisourea methyl sulfate, adding 10% dilute sulfuric acid by mass fraction into a reaction cavity through a feeding channel, wherein the volume ratio of the added dilute sulfuric acid to the reaction liquid containing O-methylisourea methyl sulfate is 3.
Example 5
The method for synthesizing O-methylisourea hydrogen sulfate provided by the embodiment comprises the following steps:
step 1, adding 2 parts by mole of dimethyl sulfate into an ultrasonic reaction kettle, adding urea and sodium carbonate into the ultrasonic reaction kettle, sequentially adding 1 part by mole of urea and 0.03 part by mole of potassium carbonate, introducing nitrogen for protection, starting an ultrasonic generator, controlling the power of the ultrasonic generator to be 550W and the frequency to be 25kHz, controlling the temperature in the reaction kettle to be 50-55 ℃, controlling the total reaction time to be 27min, recording the time when the temperature in the reaction kettle rises from room temperature to 50-55 ℃ as 0 th minute, intermittently operating the ultrasonic generator in the whole reaction time process, pausing for 1min during the 0-14 min of the operation of the ultrasonic generator, pausing for 1min from the 15-27 min of the operation of the ultrasonic generator for 2min, and reacting to obtain a reaction liquid containing O-methylisourea methyl sulfate, wherein the reaction liquid is a thick liquid;
step 2, determining the volume of the reaction liquid containing O-methylisourea methyl sulfate, adding 10% dilute sulfuric acid by mass fraction into a reaction cavity through a feeding channel, wherein the volume ratio of the added dilute sulfuric acid to the reaction liquid containing O-methylisourea methyl sulfate is 3.
Example 6
The method for synthesizing O-methylisourea hydrogen sulfate provided by the embodiment comprises the following steps:
step 1, adding 2 parts by mole of dimethyl sulfate into an ultrasonic reaction kettle, adding 1 part by mole of urea and 0.03 part by mole of cesium carbonate into the ultrasonic reaction kettle, introducing nitrogen for protection, starting an ultrasonic generator, controlling the power of the ultrasonic generator to be 550W and the frequency to be 25kHz, controlling the temperature in the reaction kettle to be 50-55 ℃, controlling the total reaction time to be 27min, recording the time when the temperature in the reaction kettle rises from room temperature to 50-55 ℃ as 0 th minute, intermittently operating the ultrasonic generator in the whole reaction time process, pausing for 1min when the ultrasonic generator operates for 0-14 min, pausing for 1min when the ultrasonic generator operates for 15-27 min, pausing for 1min when the ultrasonic generator operates for 2min when the ultrasonic generator operates for 15-27 min, and reacting to obtain a reaction solution containing O-methylisourea methyl sulfate, which is a thick liquid;
step 2, determining the volume of the reaction liquid containing O-methylisourea methyl sulfate, adding 10% of dilute sulfuric acid into a reaction cavity through a feeding channel, wherein the volume ratio of the added dilute sulfuric acid to the reaction liquid containing O-methylisourea methyl sulfate is 3.
Example 7
The method for synthesizing O-methylisourea hydrogen sulfate provided by the embodiment comprises the following steps:
step 1, adding 2 parts by mole of dimethyl sulfate into an ultrasonic reaction kettle, adding urea and sodium carbonate into the ultrasonic reaction kettle, sequentially adding 1 part by mole of urea and 0.03 part by mole of sodium carbonate, introducing nitrogen for protection, starting the ultrasonic generator, controlling the power of the ultrasonic generator to be 550W and the frequency to be 25kHz, controlling the temperature in the reaction kettle to be 50-55 ℃, controlling the total reaction time to be 27min, and continuously operating the ultrasonic generator during the reaction period to obtain a reaction liquid containing O-methyl isourea methyl sulfate as a thick liquid;
step 2, determining the volume of the reaction liquid containing O-methylisourea methyl sulfate, adding dilute sulfuric acid with the mass fraction of 10% into the reaction cavity through a feeding channel, wherein the volume ratio of the added dilute sulfuric acid to the reaction liquid containing O-methylisourea methyl sulfate is 3.
Example 8
The method for synthesizing O-methylisourea hydrogen sulfate provided by the embodiment comprises the following steps:
step 1, adding 2 parts by mole of dimethyl sulfate into an ultrasonic reaction kettle, adding urea and sodium carbonate into the ultrasonic reaction kettle, sequentially adding 1 part by mole of urea and 0.03 part by mole of sodium carbonate, introducing nitrogen for protection, starting an ultrasonic generator, controlling the power of the ultrasonic generator to be 550W and the frequency to be 25kHz, controlling the temperature in the reaction kettle to be 50-55 ℃, controlling the total reaction time to be 27min, recording the time when the temperature in the reaction kettle rises from room temperature to 50-55 ℃ as 0 th minute, intermittently operating the ultrasonic generator in the whole reaction time process, pausing for 1min during the 0-14 min of the operation of the ultrasonic generator, pausing for 1min from the 15-27 min of the operation of the ultrasonic generator for 2min, and reacting to obtain a reaction liquid containing O-methylisourea methyl sulfate, wherein the reaction liquid is a thick liquid;
step 2, determining the volume of the reaction liquid containing O-methylisourea methyl sulfate, adding 10% dilute sulfuric acid by mass fraction into a reaction cavity through a feeding channel, wherein the volume ratio of the added dilute sulfuric acid to the reaction liquid containing O-methylisourea methyl sulfate is 3.
Example 9
The method for synthesizing O-methylisourea hydrogen sulfate provided by the embodiment comprises the following steps:
step 1, adding 2 parts by mole of dimethyl sulfate into an ultrasonic reaction kettle, adding urea and sodium carbonate into the ultrasonic reaction kettle, sequentially adding 1 part by mole of urea and 0.03 part by mole of sodium carbonate, introducing nitrogen for protection, starting an ultrasonic generator, controlling the power of the ultrasonic generator to be 550W and the frequency to be 25kHz, controlling the temperature in the reaction kettle to be 50-55 ℃, controlling the total reaction time to be 27min, recording the time when the temperature in the reaction kettle rises from room temperature to 50-55 ℃ as 0 th minute, intermittently operating the ultrasonic generator in the whole reaction time process, pausing for 1min during the 0-14 min of the operation of the ultrasonic generator, pausing for 1min from the 15-27 min of the operation of the ultrasonic generator for 2min, and reacting to obtain a reaction liquid containing O-methylisourea methyl sulfate, wherein the reaction liquid is a thick liquid;
step 2, determining the volume of the reaction liquid containing O-methylisourea methyl sulfate, adding 10% dilute sulfuric acid by mass fraction into a reaction cavity through a feeding channel, wherein the volume ratio of the added dilute sulfuric acid to the reaction liquid containing O-methylisourea methyl sulfate is 3.
Example 10
The method for synthesizing O-methylisourea hydrogen sulfate provided by the embodiment comprises the following steps:
step 1, adding 2 parts by mole of dimethyl sulfate into an ultrasonic reaction kettle, adding urea and sodium carbonate into the ultrasonic reaction kettle, sequentially adding 1 part by mole of urea and 0.03 part by mole of sodium carbonate, introducing nitrogen for protection, starting an ultrasonic generator, controlling the power of the ultrasonic generator to be 550W and the frequency to be 25kHz, controlling the temperature in the reaction kettle to be 50-55 ℃, controlling the total reaction time to be 27min, recording the time when the temperature in the reaction kettle rises from room temperature to 50-55 ℃ as 0 th minute, intermittently operating the ultrasonic generator in the whole reaction time process, pausing for 1min during the 0-14 min of the operation of the ultrasonic generator, pausing for 1min from the 15-27 min of the operation of the ultrasonic generator for 2min, and reacting to obtain a reaction liquid containing O-methylisourea methyl sulfate, wherein the reaction liquid is a thick liquid;
step 2, determining the volume of the reaction liquid containing O-methylisourea methyl sulfate, adding 10% dilute sulfuric acid by mass fraction into a reaction cavity through a feeding channel, wherein the volume ratio of the added dilute sulfuric acid to the reaction liquid containing O-methylisourea methyl sulfate is 3.
FIG. 2 is a high performance liquid chromatogram of O-methylisourea hydrogen sulfate obtained in example 10 of the present application.
As is clear from FIG. 2, the purity of O-methylisourea hydrogen sulfate obtained in this example was 98.7%.
Example 11
The method for synthesizing O-methylisourea hydrogen sulfate provided by the embodiment comprises the following steps:
step 1, adding 2 parts by mole of dimethyl sulfate into an ultrasonic reaction kettle, adding urea and sodium carbonate into the ultrasonic reaction kettle, sequentially adding 1 part by mole of urea and 0.03 part by mole of sodium carbonate, introducing nitrogen for protection, starting an ultrasonic generator, controlling the power of the ultrasonic generator to be 550W and the frequency to be 25kHz, controlling the temperature in the reaction kettle to be 50-55 ℃, controlling the total reaction time to be 27min, recording the time when the temperature in the reaction kettle rises from room temperature to 50-55 ℃ as 0 th minute, intermittently operating the ultrasonic generator in the whole reaction time process, pausing for 1min during the 0-14 min of the operation of the ultrasonic generator, pausing for 1min from the 15-27 min of the operation of the ultrasonic generator for 2min, and reacting to obtain a reaction liquid containing O-methylisourea methyl sulfate, wherein the reaction liquid is a thick liquid;
step 2, determining the volume of the reaction liquid containing O-methylisourea methyl sulfate, adding 10% dilute sulfuric acid by mass fraction into a reaction cavity through a feeding channel, wherein the volume ratio of the added dilute sulfuric acid to the reaction liquid containing O-methylisourea methyl sulfate is 3.
FIG. 3 is a high performance liquid chromatogram of O-methylisourea hydrogen sulfate obtained in example 11 of the present application.
As is clear from FIG. 3, the purity of O-methylisourea hydrogen sulfate obtained in this example was 98.4%.
Comparative example 1
The method for synthesizing O-methylisourea hydrogen sulfate provided by the comparative example comprises the following steps:
step 1, adding 2 parts by mole of dimethyl sulfate into an ultrasonic reactor, adding urea and sodium carbonate into a conventional reaction kettle, sequentially adding 1 part by mole of urea and 0.03 part by mole of sodium carbonate, introducing nitrogen for protection, controlling the temperature in the reaction kettle at 100-105 ℃, controlling the total reaction time to be 2 hours, and reacting to obtain a reaction liquid containing O-methyl isourea methyl sulfate, wherein the reaction liquid is a thick liquid;
step 2, determining the volume of the reaction liquid containing O-methylisourea methyl sulfate, adding dilute sulfuric acid with the mass fraction of 10%, controlling the volume ratio of the added dilute sulfuric acid to the reaction liquid containing O-methylisourea methyl sulfate to be 3, controlling the reaction temperature to be 70 ℃ for hydrolysis, controlling the reaction time to be 3h, after the reaction is finished, cooling the collected materials to-5 ℃, standing for 8 hours, performing suction filtration, taking the solid, and recrystallizing the obtained solid by using methanol to obtain the target product O-methylisourea hydrogen sulfate, wherein the total yield is 50.5% by urea, and the purity reaches 92.4%.
Comparative example 2
The method for synthesizing O-methylisourea hydrogen sulfate provided by the comparative example comprises the following steps:
step 1, adding 3 parts by mole of dimethyl sulfate into an ultrasonic reaction kettle, adding urea and sodium carbonate into the ultrasonic reaction kettle, sequentially adding 1 part by mole of urea and 0.03 part by mole of sodium carbonate, introducing nitrogen for protection, controlling the temperature in the reaction kettle at 100-105 ℃, controlling the total reaction time to be 2 hours, and reacting to obtain a reaction solution containing O-methyl isourea methyl sulfate, wherein the reaction solution is a thick liquid;
step 2, determining the volume of the reaction liquid containing O-methylisourea methyl sulfate, adding dilute sulfuric acid with the mass fraction of 10%, controlling the volume ratio of the added dilute sulfuric acid to the reaction liquid containing O-methylisourea methyl sulfate to be 3, controlling the reaction temperature to be 70 ℃ for hydrolysis, controlling the reaction time to be 3h, after the reaction is finished, cooling the collected materials to-5 ℃, standing for 8 hours, performing suction filtration, taking the solid, and recrystallizing the obtained solid by using methanol to obtain the target product O-methylisourea hydrogen sulfate, wherein the total yield is 53.7% by urea, and the purity reaches 92.8%.
Effects and effects of the embodiments
According to the method for synthesizing the O-methylisourea hydrogen sulfate provided by the embodiment, due to the fact that the ultrasonic waves are creatively used for promoting the reaction, the reaction temperature can be reduced from about 100 ℃ to 50-55 ℃, the side reaction can be reduced and the yield can be improved due to the reduction of the reaction temperature, the reaction can be safer, and the yield of the product can be improved by more than 90%.
Furthermore, since a small amount of t-butyl methyl ether is added to the recrystallization agent, the purity of the product can be effectively improved while the yield is kept almost not lowered.
Furthermore, because a specially-made reaction kettle is used as a reaction container, an automatic continuous production flow can be realized in the reaction process, and the products can be automatically and continuously fed, reacted and collected, so that the whole reaction efficiency is improved.
Although the present invention has been described with reference to the preferred embodiments, it should be understood that various changes and modifications can be made therein by those skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.
Claims (7)
1. A method for synthesizing O-methylisourea hydrogen sulfate is characterized by comprising the following steps:
step 1, dimethyl sulfate, urea and a catalyst react in a reaction container with an ultrasonic device to obtain reaction liquid containing O-methylisourea methyl sulfate; the catalyst is sodium carbonate; the ultrasonic power of the ultrasonic device is 500w-550w, and the ultrasonic frequency is 20kHz-25kHz; controlling the reaction temperature at 50-55 ℃, the reaction time at m minutes, pausing for q minutes every time an ultrasonic device works for p minutes within 0-n minutes after the reaction starts, pausing for v minutes every time the ultrasonic device works for u minutes within n-m minutes, wherein m is more than or equal to 20 and less than or equal to 30, n is more than or equal to 5 and less than or equal to m/2, p is more than or equal to 0.5 and less than or equal to 1, q is more than 0 and less than or equal to 1, u is more than or equal to 0.5 and less than or equal to 2, and v is more than 0 and less than or equal to 1;
step 2, hydrolyzing the reaction solution containing O-methylisourea methyl sulfate by acid under the ultrasonic condition to prepare O-methylisourea hydrogen sulfate; the ultrasonic wave adopts intermittent ultrasonic wave, the reaction time is m minutes, the ultrasonic device pauses for q minutes every p minutes when the ultrasonic device works within 0-n minutes after the reaction starts, the ultrasonic device pauses for v minutes every u minutes when the ultrasonic device works within n-m minutes, m is more than or equal to 20 and less than or equal to 30, n is more than or equal to 5 and less than or equal to m/2, p is more than or equal to 0.5 and less than or equal to 1, q is more than 0 and less than or equal to 1, u is more than or equal to 0.5 and less than or equal to 2, and v is more than 0 and less than or equal to 1.
2. A method of synthesizing O-methylisourea hydrogen sulfate according to claim 1, characterized in that: wherein, the acid adopted by the acid hydrolysis in the step 2 is a sulfuric acid aqueous solution with the mass fraction of 10% -49%.
3. A method of synthesizing O-methylisourea hydrogen sulfate according to claim 2, characterized in that:
wherein the volume ratio of the reaction liquid containing O-methylisourea methyl sulfate to the acid in the step 2 is 1: (1-3).
4. A method of synthesizing O-methylisourea hydrogen sulfate according to claim 1, characterized in that:
wherein the molar ratio of the dimethyl sulfate to the urea to the catalyst is (1.0-4.0): 1: (0.01-0.5).
5. A method of synthesizing O-methylisourea hydrogen sulfate according to claim 1, characterized in that:
wherein the reaction vessel comprises:
a reaction cavity is formed in the kettle body;
the ultrasonic generator is arranged at the bottom of the kettle body and is used for emitting ultrasonic waves into the reaction cavity during reaction;
the feeding pipeline is provided with a feeding valve, is arranged on the upper side of the kettle body and is communicated with the reaction cavity;
the discharging channel is provided with a discharging valve, is arranged at the lower side of the kettle body and is communicated with the reaction cavity;
the exhaust pipeline is arranged at the top of the kettle body and is communicated with the reaction cavity; and
and the circulating channel is arranged in the reaction cavity.
6. A method of synthesizing O-methylisourea hydrogen sulfate according to claim 1, characterized in that:
wherein, the step 2 also comprises the following steps:
adding acid into O-methyl isourea methyl sulfate, hydrolyzing at 20-25 ℃, cooling to 0-5 ℃ after the reaction is finished, standing for 8-10 h, filtering to obtain a crude O-methyl isourea hydrogen sulfate product, and recrystallizing the crude O-methyl isourea hydrogen sulfate product by using a recrystallization agent to obtain the O-methyl isourea hydrogen sulfate.
7. The method for synthesizing O-methylisourea hydrogen sulfate according to claim 6, characterized in that:
wherein the recrystallization agent is any one or more of methanol, ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, tetrahydrofuran, acetonitrile, tert-butyl methyl ether or acetone.
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| US3931316A (en) * | 1974-08-10 | 1976-01-06 | Suddeutsche Kalkstickstoff-Werke Ag | Method of preparing O-methyl-isourea hydrogen sulfate and O-methyl-isourea sulfate from cyanamide |
| KR100584629B1 (en) * | 1997-12-24 | 2006-05-30 | 스미카 다케다 노야쿠 가부시키가이샤 | Method for producing isoureas |
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| WO2004067500A1 (en) * | 2003-01-29 | 2004-08-12 | Nippon Carbide Kogyo Kabushiki Kaisha | Novel o-isopropylisourea salts and process for the production thereof |
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