CONTINUOUS-FLOW SYNTHESIS METHOD OF 13C-UREA

Abstract

A continuous-flow synthesis method of .sup.13C-urea, including: (S1) mixing sulphur and a methanol solution containing NH.sub.3 in a feed kettle to obtain a slurry; or mixing ammonia gas, sulphur and methanol in a feed kettle to obtain a slurry; (S2) feeding the slurry into a mixing unit; and feeding .sup.13CO into the mixing unit to obtain a three-phase mixture; (S3) mixing the three-phase mixture in the mixing unit evenly; feeding the three-phase mixture into a continuous-flow reactor for reaction to obtain a reaction product; and (S4) feeding the reaction product into a gas-liquid separator for gas-liquid separation, and collecting a liquid phase as a crude product solution; and subjecting the liquid phase to purification to obtain the .sup.13C-urea.

Claims

1. A continuous-flow synthesis method of .sup.13C-urea, comprising: (S1) mixing sulphur and a methanol solution containing NH.sub.3 in a feed kettle to obtain a slurry; or mixing ammonia gas (NH.sub.3), sulphur and methanol in a feed kettle to obtain a slurry; (S2) feeding the slurry into a mixing unit; and feeding .sup.13CO into the mixing unit to obtain a three-phase mixture; (S3) mixing the three-phase mixture in the mixing unit evenly; and feeding the three-phase mixture into a continuous-flow reactor for reaction to obtain a reaction product; and (S4) feeding the reaction product into a gas-liquid separator for gas-liquid separation, and collecting a liquid phase; subjecting the liquid phase to purification to obtain the .sup.13C-urea.

2. The continuous-flow synthesis method of claim 1, wherein a molar ratio of the sulphur to NH.sub.3 to .sup.13CO is (1-5):(2-50):1.

3. The continuous-flow synthesis method of claim 1, wherein the continuous-flow reactor is controlled to 0-5 MPa and 50-150° C.

4. The continuous-flow synthesis method of claim 1, wherein in step (S2), a flow rate of the slurry is 0.001-10 L/min; and a flow rate of the .sup.13CO is 0.001-100 L/min.

5. The continuous-flow synthesis method of claim 1, wherein a residence time of the three-phase mixture in the continuous-flow reactor is 1-120 min.

6. The continuous-flow synthesis method of claim 1, wherein in step (S4), the purification is performed through steps of: subjecting the liquid phase to rotary evaporation in a rotary evaporator, dissolving with an alcohol or water, and vacuum filtration to collect a filtrate; and drying the filtrate to obtain the .sup.13C-urea.

7. The continuous-flow synthesis method of claim 6, wherein a purity of the .sup.13C-urea after purification is 99%.

8. The continuous-flow synthesis method of claim 1, wherein a .sup.13CO conversion rate is 95-100%; and a .sup.13C-urea yield is 90-95%.

9. The continuous-flow synthesis method of claim 1, wherein a heat exchange medium of the continuous-flow reactor is heat-conducting oil or a water-based heat-conducting medium; and the water-based heat-conducting medium is water, a 1,2-ethanediol binary aqueous solution or a 1,2-propanediol binary aqueous solution.

10. The continuous-flow synthesis method of claim 1, wherein the slurry is fed by a feed pump into the mixing unit; the .sup.13CO passes through a pressure reducing valve to enter the mixing unit, wherein a flow of the .sup.13CO is controlled by a flow controller; and the reaction product flowing out from the continuous-flow reactor enters the gas-liquid separator through a back pressure valve.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The drawings needed in the description of the embodiments of the disclosure or the prior art will be briefly described below to explain technical solutions of the embodiments of the present disclosure or the prior art more clearly. Obviously, presented in the accompany drawings are merely some embodiments of the present disclosure, and other drawings can be obtained by those skilled in the art based on the drawings provided herein without paying creative effort.

[0031] This FIGURE is a flow chart of a continuous-flow synthesis method of .sup.13C-urea according to an embodiment of the present disclosure.

[0032] Implementation, features and advantages will be further illustrated below with reference to the accompany drawing and embodiments.

DETAILED DESCRIPTION OF EMBODIMENTS

[0033] Technical solutions of the present disclosure will be clearly and completely described below with reference to the embodiments and accompanying drawings. Obviously, described below are merely some embodiments of this disclosure, and are not intended to limit the disclosure. Other embodiments obtained by those skilled in the art based on the embodiments provided herein without paying any creative effort should fall within the scope of the present disclosure.

[0034] Unless otherwise specified, the materials and reagents in the following embodiments are available commercially, and the experiments are performed by conventional methods. For the quantitative analysis, three replicates are performed, and the results are expressed as mean or mean±standard deviation.

[0035] As used herein, the “and/or” includes three solutions, for example, “A and/or B” includes A, B and a combination thereof. Additionally, technical solutions of various embodiments can be combined on the premise that the combined technical solution can be implemented by those skilled in the art. When the combination of technical solutions is contradictory or cannot be implemented, such a combination does not exist, and does not fall within the scope of the present disclosure.

[0036] Described herein was a continuous-flow synthesis method of .sup.13C-urea, including steps of:

[0037] (S1) mixing sulphur and a methanol solution containing NH.sub.3 in a feed kettle to obtain a slurry; or mixing ammonia gas (NH.sub.3), sulphur and methanol in a feed kettle to obtain a slurry;

[0038] (S2) feeding the slurry into a mixing unit; and feeding .sup.13CO into the mixing unit to obtain a three-phase mixture;

[0039] (S3) mixing the three-phase mixture in the mixing unit evenly; and feeding the three-phase mixture into a continuous-flow reactor for reaction to obtain a reaction product; and

[0040] (S4) feeding the reaction product into a gas-liquid separator for gas-liquid separation, and collecting a liquid phase; subjecting the liquid phase to purification to obtain the .sup.13C-urea.

[0041] By replacing a kettle reactor with the continuous-flow reactor, a reaction time of continuous-flow synthesis is reduced from hours to minutes, significantly developing the reaction rate. In addition, the raw materials react in the continuous-flow reactor, contributing to a full contact therebetween. Particularly, the continuous-flow synthesis method using the continuous-flow reactor does not require gas compression into the reactor as opposed to the traditional kettle reactor reaction, shorting a process time, and improving a reaction efficiency.

[0042] Since a gas-phase raw material in the continuous-flow synthesis method is .sup.13CO, the pressure in the continuous-flow reactor keeps constant during reaction and will not affect the reaction. To the contrary, regarding the reaction in the kettle reactor, .sup.13CO therein will be consumed constantly, therefore, it is difficult to maintain the initial pressure in the reactor at the later stage of the reaction, resulting in reaction rate decreases and affecting the reaction efficiency.

[0043] In an embodiment, a molar ratio of the sulphur to NH.sub.3 to .sup.13CO is (1-5):(2-50):1.

[0044] In an embodiment, the continuous-flow reactor is controlled to 0-5 MPa and 50-150° C.

[0045] In an embodiment, in step (S2), a flow rate of the slurry is 0.001-10 L/min; and a flow rate of the .sup.13CO is 0.001-100 L/min.

[0046] In an embodiment, a residence time of the three-phase mixture in the continuous-flow reactor is 1-120 min.

[0047] By using the above-mentioned technology solutions, the reaction time will be greatly reduced compared with traditional kettle-reactor reaction.

[0048] In an embodiment, in step (S4), the purification is performed through the following steps.

[0049] The liquid phase is subjected to rotary evaporation in a rotary evaporator, dissolving with an alcohol or water, and vacuum filtration to collect a filtrate. Then the filtrate is dried to obtain the .sup.13C-urea.

[0050] In an embodiment, a purity of the .sup.13C-urea after purification is 99%.

[0051] By using the above-mentioned technology solutions, the product yield is high.

[0052] In an embodiment, a .sup.13CO conversion rate is 95-100%; and a .sup.13C-urea yield is 90-95%.

[0053] In an embodiment, a heat exchange medium of the continuous-flow reactor is heat-conducting oil or a water-based heat-conducting medium; and the water-based heat-conducting medium is water, a 1,2-ethanediol binary aqueous solution or a 1,2-propanediol binary aqueous solution.

[0054] In an embodiment, the slurry is fed by a feed pump into the mixing unit; the .sup.13CO passes through a pressure reducing valve to enter the mixing unit, wherein a flow of the .sup.13CO is controlled by a flow controller; and the reaction product flowing out from the continuous-flow reactor enters the gas-liquid separator through a back pressure valve.

[0055] By using the above-mentioned technology solutions, the flow of the slurry and that of .sup.13CO can be precisely controlled, thereby precisely controlling a reaction process.

[0056] In an embodiment, the continuous-flow synthesis method further includes a step of gas leak detection. The .sup.13C-urea is synthesized in an operating room, which is kept in negative pressure by using an evacuating device. The evacuating device is communicated with an evacuating pipe. The operating room and the evacuating pipe are respectively provided with an ammonia sensing probe, a carbon monoxide sensing probe, and a hydrogen sulfide sensing probe. When levels of ammonia and/or carbon monoxide and/or hydrogen sulfide exceed a preset value, it indicates a possible gas leak. Since ammonia, carbon monoxide and hydrogen sulfide are hazardous to the health of operators, the system will give an alarm or a corresponding valve is immediately closed. The operators need to monitor and repair the pipe before continuing with the urea synthesis process.

[0057] The above-mentioned technology solutions can protect the operator from being damaged ammonia, carbon monoxide and hydrogen sulfide.

[0058] In summary, by means of the continuous-flow reactor, the continuous-flow synthesis method provided herein has novelty, simple operation, high product quality and yield, thereby leading to low cost and less pollution. By means of the continuous-flow reactor, the cost is greatly reduced. This application has simple operation, relatively mild reaction conditions, and relatively low pollution. The continuous-flow synthesis method provided herein effectively overcomes the defects of existing reactions that cannot be produced on a larger scale, facilitating large-scale production and improving quality and yield of the .sup.13C-urea.

EXAMPLE 1

[0059] (S1) 71.4 g of sulphur, 1200 mL of a methanol solution containing 7 mol/L of NH.sub.3 and 1000 mL of methanol were fed into a feed kettle, and then mixed to obtain a slurry.

[0060] (S2) The slurry was fed by a feed pump into a mixing unit, to which .sup.13CO was fed after passing through a pressure reducing valve, so as to obtain a three-phase mixture, where a flow rate of the .sup.13CO was controlled at 0.1 L/min by a flow controller, and a flow rate of the slurry was 40 mL/min.

[0061] (S3) The three-phase mixture was mixed evenly in the mixing unit, fed into a continuous-flow reactor, and reacted at 130° C. and 3 MPa for 20 min to obtain a reaction product.

[0062] (S4) The reaction product was cooled by a cooling coil in an ice-water bath, and then flowed out of the continuous-flow reactor as a brown liquid to enter a gas-liquid separator for separation. A liquid phase was collected as a crude product solution, and subjected to rotary evaporation in a rotary evaporator, dissolving with water and vacuum filtration to collect a filtrate. The filtrate was dried to obtain .sup.13C-urea. The gas phase generated from the gas-liquid separation was discharged and absorbed with a NaOH solution.

[0063] Examples 2-5 were performed according to the steps of Example 1. The amounts of raw materials and the reaction parameters of Examples 2-5 were shown in Table 1.

TABLE-US-00001 TABLE 1 Amounts of raw materials and reaction parameters of Examples 1-5 Exam- Exam- Exam- Exam- Exam- ple 1 ple 2 ple 3 ple 4 ple 5 Sulphur/g 71.4 7.4 357 1071 3570 Volume of the NH.sub.3- 1200 120 4000 12000 40000 containing methanol solution/mL Concentration of 7 7 7 7 7 NH.sub.3 in the methanol solution/mol .Math. L.sup.−1 Volume of ethanol 1000 100 21000 63000 210000 solution/mL Flow rate of slurry/ 40 4 200 600 2000 mL .Math. min.sup.−1 Flow rate of .sup.13CO/ 0.1 0.01 1 3 15 L .Math. min.sup.−1 Reaction 130 110 100 120 110 temperature/° C. Pressure/MPa 3 1 1 1 1 Residence time/min 20 20 40 40 40 .sup.13C-urea yields and .sup.13CO conversion rates of Examples 1-5 were shown in Table 2.

TABLE-US-00002 TABLE 2 .sup.13C-urea yields and .sup.13CO conversion rates of Examples 1-5 Exam- Exam- Exam- Exam- Exam- ple 1 ple 2 ple 3 ple 4 ple 5 .sup.13C-urea yield/% 92.3 90.1 94.1 91.7 90.8 .sup.13CO conversion rate/% 100 98 100 98 96

[0064] Comparative Examples 1-2 were performed basically according to the steps of Example 1.

[0065] Regarding Comparative Example 1, a slurry obtained in step (S1) and .sup.13CO were directly fed into the continuous-flow reactor for reaction.

[0066] Regarding Comparative Example 2, it was free from addition of 1000 mL of methanol in step (S1).

[0067] .sup.13C-urea yields and .sup.13CO conversion rates of Comparative Examples 1-2 are shown in Table 3.

TABLE-US-00003 TABLE 3 .sup.13C-urea yields and .sup.13CO conversion rates of Comparative Examples 1-2 Comparative Comparative Example 1 Example 2 .sup.13C-urea yield/% 79.6 89.4 .sup.13CO conversion rate/% 87 92

[0068] Technical solutions of various embodiments can be combined on the premise that the combined technical solution can be implemented by those skilled in the art. When the combination of technical solutions is contradictory or cannot be implemented, such a combination does not exist, and does not fall within the scope of the present disclosure.

[0069] Described above are only some embodiments of the present disclosure, which are not intended to limit the disclosure. Any variations and modifications made by those of ordinary skilled in the art without departing from the spirit of the disclosure should fall within the scope of the disclosure defined by the appended claims.