Method for preparing pharmaceutical grade dicyandiamide by urea pyrolysis

Abstract

The application belongs to the technical field of medical chemistry synthesis, and particularly relates to a method for preparing medical-grade dicyandiamide by urea pyrolysis. The method comprises a process for preparing a hydrogen-containing intermediate and a process for preparing dicyandiamide from the hydrogen-containing intermediate. The process for preparing the hydrogen-containing intermediate comprises continuously co-feeding urea and alkaline earth metal oxide into a dynamic sealing reaction system at a molar ratio of 2.05:1.00 to 2.15:1.00, sequentially passing through three thermal zone reactions, and obtaining a cyanogen-containing intermediate. Experiments show that reasonable molar ratio control combined with three thermal zone reactions can reduce side reactions and impurity accumulation caused by feeding imbalance, and reduce the risk of melamine generation from the source. When the molar ratio of urea and alkaline earth metal oxide is 2.10:1.00, the purity of the obtained dicyandiamide is 99.88%, the melamine content is less than 0.01%, and the heavy metal content is 2g / 100g, all of which meet the quality requirements of medical grade.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical chemical synthesis technology, specifically relating to a method for preparing pharmaceutical-grade dicyandiamide by urea pyrolysis. Background Technology

[0002] Dicyandiamide (DCDA) is a key precursor to an active pharmaceutical ingredient (API), an important intermediate in fine chemicals and pharmaceuticals, and a crucial precursor for the preparation of drugs such as metformin hydrochloride. Current technologies for preparing dicyandiamide via urea pyrolysis typically involve urea thermal decomposition, formation of a cyanide-containing intermediate, subsequent hydrolysis and dimerization, and then crystallization and purification to obtain the target product.

[0003] Existing publicly available routes mainly focus on urea cracking, polymerization, and crystallization. However, impurities and other factors generated during urea cracking can easily lead to low purity of the prepared dicyandiamide, which cannot meet the purity requirements for pharmaceutical grade. Summary of the Invention

[0004] Based on this, this application provides a method for preparing pharmaceutical-grade dicyandiamide by urea pyrolysis, in order to solve the technical problem that the dicyandiamide prepared in the prior art has low purity and cannot meet the purity requirements of pharmaceutical grade.

[0005] The technical solution to the above-mentioned technical problems in this application is as follows: A method for preparing pharmaceutical-grade dicyandiamide by urea pyrolysis includes a process for preparing a hydrogen-containing intermediate and a process for preparing dicyandiamide from the hydrogen-containing intermediate. The process for preparing the hydrogen-containing intermediate includes: continuously co-feeding urea and alkaline earth metal oxide into a dynamically sealed reaction system at a molar ratio of 2.05:1.00 to 2.15:1.00, sequentially passing them through a first hot zone at a temperature of 180°C to 220°C and a residence time of 15 to 30 min; a second hot zone at a temperature of 300°C to 350°C and a residence time of 45 to 90 min; and a third hot zone at a temperature of 580°C to 620°C and a residence time of 20 to 40 min, to obtain a cyanide-containing intermediate.

[0006] Preferably, in the above method for preparing pharmaceutical-grade dicyandiamide by pyrolysis of urea, the alkaline earth metal oxide includes at least one of beryllium oxide, magnesium oxide, calcium oxide, strontium oxide, and barium oxide.

[0007] Preferably, in the above method for preparing pharmaceutical-grade dicyandiamide by urea pyrolysis, the process of preparing dicyandiamide from the hydrogen-containing intermediate includes the following steps: The cyanide-containing intermediate was hydrolyzed to obtain monocyanamide; The monocyanamide was subjected to a dimerization reaction to obtain crude dicyanamide; The crude dicyandiamide was dissolved, filtered, and recrystallized to obtain the finished dicyandiamide.

[0008] Preferably, in the above method for preparing pharmaceutical-grade dicyandiamide by pyrolysis of urea, the specified pressure is 0.1 to 0.3 MPa.

[0009] Preferably, in the above method for preparing pharmaceutical-grade dicyandiamide by urea pyrolysis, the dimerization process uses a buffer system to maintain the pH of the dimerization reaction system between 8.8 and 9.2, and forces a continuous cooling gradient of 1.5°C to 2.5°C / min.

[0010] Preferably, in the above method for preparing pharmaceutical-grade dicyandiamide by pyrolysis of urea, the filtration is performed using a polyethersulfone membrane with a pore size ≤ 0.22 μm for purification.

[0011] Preferably, in the above method for preparing pharmaceutical-grade dicyandiamide by pyrolysis of urea, the process of preparing the hydrogen-containing intermediate includes: continuously feeding urea, alkaline earth metal oxide and scale inhibitor into a dynamic sealed continuous rotary kiln for pyrolysis reaction, wherein the scale inhibitor accounts for 0.1% to 5% of the weight of the alkaline earth metal oxide.

[0012] Preferably, in the above method for preparing pharmaceutical-grade dicyandiamide by urea pyrolysis, the scale inhibitor dopant includes either silicon dioxide or titanium dioxide.

[0013] Preferably, in the above method for preparing pharmaceutical-grade dicyandiamide by urea pyrolysis, the scale inhibitor is a mixture of silicon dioxide and titanium dioxide, wherein the mass ratio of silicon dioxide to titanium dioxide is (1:10) to (10:1).

[0014] Compared with the prior art, this application has at least the following advantages: This application discloses a method for preparing pharmaceutical-grade dicyandiamide by pyrolysis of urea, comprising continuously co-feeding urea and alkaline earth metal oxide into a dynamic sealed reaction system at a molar ratio of 2.05:1.00 to 2.15:1.00, and sequentially passing them through a first hot zone at a temperature of 180°C to 220°C and a residence time of 15 to 30 min; a second hot zone at a temperature of 300°C to 350°C and a residence time of 45 to 90 min; and a third hot zone at a temperature of 580°C to 620°C and a residence time of 20 to 40 min, to obtain a cyanide-containing intermediate. Experiments show that reasonable molar ratio control, combined with the reaction in the three hot zones, can reduce side reactions and impurity accumulation caused by feed imbalance, thereby reducing the risk of melamine formation from the source. In particular, when the molar ratio of urea to alkaline earth metal oxide is 2.10:1.00, the purity of the obtained dicyandiamide is 99.88%, the melamine content is <0.01%, and the heavy metal content is 2g / 100g, all of which meet the pharmaceutical grade quality requirements. Attached Figure Description

[0015] Figure 1This is a process flow diagram for preparing pharmaceutical-grade dicyandiamide by pyrolysis of urea in Experimental Example 1 of this application.

[0016] Figure 2 This is a schematic diagram of the dimerization reaction section and the continuous cooling control unit.

[0017] Figure 3 This is a schematic diagram of the preparation of pharmaceutical-grade dicyandiamide by urea pyrolysis in Experimental Example 2 of this application.

[0018] Figure 4 A schematic diagram of a dynamic sealing continuous rotary kiln and its three-temperature zone layout.

[0019] Figure 5 This is a schematic diagram of the preparation of pharmaceutical-grade dicyandiamide by pyrolysis of urea in Experimental Example 3 of this application.

[0020] Figure 6 This is a schematic diagram of the raw material mixing and pyrolysis reaction system in Experiment Example 3 of this application. Detailed Implementation

[0021] It should be noted that, unless otherwise specified, the embodiments and features described in the embodiments of the present invention can be combined with each other. The technical solutions of the present invention will be further described below with reference to the accompanying drawings of the embodiments of the present invention. The present invention is not limited to the following specific embodiments.

[0022] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in this specification is for the purpose of describing particular embodiments only and is not intended to be limiting of this application. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0023] Please see Figures 1 to 6 In one specific embodiment of this application, a method for preparing pharmaceutical-grade dicyandiamide by urea pyrolysis includes a process for preparing a hydrogen-containing intermediate and a process for preparing dicyandiamide from the hydrogen-containing intermediate. The process for preparing the hydrogen-containing intermediate includes: continuously co-feeding urea and alkaline earth metal oxide into a dynamic sealed reaction system at a molar ratio of 2.05:1.00 to 2.15:1.00, sequentially passing through a first hot zone at a temperature of 180°C to 220°C and a residence time of 15 to 30 min; a second hot zone at a temperature of 300°C to 350°C and a residence time of 45 to 90 min; and a third hot zone at a temperature of 580°C to 620°C and a residence time of 20 to 40 min, to obtain a cyanic intermediate, which is an isocyanate melt.

[0024] When the molar ratio of urea to alkaline earth metal oxides is too low, insufficient urea leads to incomplete conversion of alkaline earth metal oxides and abnormal alkalinity in the system. When the molar ratio of urea to alkaline earth metal oxides is too high, excessive decomposition byproducts are introduced, increasing the risk of impurities such as biuret, triuret, and melamine.

[0025] The dynamic sealed reaction system is a dynamic sealed continuous rotary kiln equipped with an inert gas mechanical purging seal (to maintain a slight positive pressure) and internal spiral baffles (to ensure uniform thermal residence time). The primary pyrolysis of the mixture of urea and alkaline earth metal oxides takes place in this dynamic sealed continuous rotary kiln equipped with an inert gas (nitrogen) purging seal. Three independent hot zones allow the urea thermal decomposition, intermediate conversion, and high-temperature solid-phase reaction to proceed in an orderly and continuous manner at different temperature stages. The first hot zone (180°C to 220°C) is the urea melting and initial decomposition stage: this temperature range is slightly above the melting point of urea (approximately 133°C), primarily used to promote the conversion of solid urea to a molten state and initiate thermal decomposition, initially releasing ammonia (NH3) and isocyanate (HNCO). Maintaining a temperature below 220℃ helps maintain a stable initial decomposition rate, preventing side reactions (such as excessive biuret or cyanuric acid formation) caused by localized overheating before the material is fully mixed with the alkaline earth metal oxides. Setting a shorter time (15 to 30 minutes) also effectively prevents the formation of byproducts such as biuret or cyanuric acid due to prolonged residence before the material is uniformly mixed. The second thermal zone (300℃ to 350℃) is the gas-solid contact and intermediate conversion stage: this temperature zone is the core reaction section for achieving high yields. A large amount of HNCO gas is generated in this stage, and it undergoes chemical adsorption and conversion with the solid alkaline earth metal oxides. In conjunction with a positive pressure environment of 0.1 to 0.3 MPa, the thermodynamic conditions in this temperature zone help overcome gas film resistance, promoting the diffusion of HNCO into the solid matrix and its reaction, effectively reducing the volatilization and escape loss of intermediate gases. The gas-solid phase diffusion reaction is usually the rate-limiting step in this type of pyrolysis process. Therefore, setting the residence time in this zone to the maximum (45 to 90 minutes) has sufficient thermodynamic and kinetic basis and is a necessary condition to ensure high yield. The third hot zone (580℃ to 620℃) is the high-temperature solid-state transformation and stabilization stage: the intermediates generated in the early stage complete the final solid-state lattice recombination and complete transformation at this high temperature, generating the target pyrolysis product. 580℃ to 620℃ can ensure complete conversion in reaction kinetics. Setting 620℃ as the upper limit aims to avoid deep thermal degradation and carbonization of materials at excessively high temperatures, or irreversible high-temperature thermal stress damage to the inner wall of the equipment and the internal spiral baffle. Setting a shorter time (20 to 40 minutes) can ensure complete conversion and prevent equipment damage due to long-term high-temperature thermal stress. Compared to conventional two-stage direct heating, the three-stage temperature control of 180-220℃, 300-350℃, and 580-620℃ in this invention avoids the violent pyrolysis of urea at 300℃ and the large-scale escape of isocyanate, alleviates thermal agglomeration, and improves the final yield.

[0026] Experiments show that strict control of the molar ratio can reduce side reactions and impurity accumulation caused by feed imbalance, thereby reducing the risk of melamine formation at the source. In particular, when the molar ratio of urea to alkaline earth metal oxide is 2.10:1.00, the purity of dicyandiamide is 99.88%, the impurity content is as low as <0.01%, and the heavy metal content is 2g / 100g, all exceeding pharmaceutical-grade requirements (purity 99.80%, heavy metal content ≤10g / 100g, melamine ≤0.01g / 100g). Therefore, the molar ratio of urea to alkaline earth metal oxide is 1.90:1.00 to 2.10:1.00, preferably 2.05:1.00 to 2.15:1.00. Preferably, the alkaline earth metal oxide includes any one of beryllium oxide (BeO), magnesium oxide (MgO), calcium oxide (CaO), strontium oxide (SrO), and barium oxide (BaO), with calcium oxide being preferred in this application.

[0027] Preferably, the pressure in the dynamically sealed reaction system is 0.1 to 0.3 MPa. Gas-film resistance is the rate-limiting step in urea pyrolysis. In this application, a micro-positive pressure of 0.01 to 0.3 MPa is maintained in the dynamically sealed continuous rotary kiln, that is, a micro-positive pressure of 0.01 to 0.3 MPa is maintained in the dynamically sealed continuous rotary kiln by purging with inert gas. This pressure helps to reduce the escape of volatile isocyanate (HNCO) during pyrolysis and promotes its further reaction with the solid matrix (alkaline earth metal oxide matrix), thereby improving feedstock utilization and dicyandiamide yield. Preferably, a micro-positive pressure of 0.1 to 0.3 MPa is maintained in the dynamically sealed continuous rotary kiln by introducing inert gas. Experiments show that under 0 MPa (normal pressure), HNCO volatilization and loss are severe, and the dicyandiamide yield is only 68.0%; a slight positive pressure of 0.2 MPa provides the thermodynamic driving force to overcome the gas film resistance, and the yield of the obtained dicyandiamide is increased to 93.5% while ensuring its purity of 99.88%.

[0028] In a preferred embodiment, the process of preparing dicyandiamide from the hydrogen-containing intermediate includes: hydrolyzing the cyanide-containing intermediate to obtain monocyanamide; and subjecting the monocyanamide to a dimerization reaction to obtain crude dicyandiamide. If the pH is not controlled stably or the cooling rate is not reasonable during the dimerization stage, the content of toxic melamine byproducts can easily increase, making it difficult for the product to meet pharmaceutical grade requirements. Therefore, a buffer system is used in the dimerization process to strictly maintain the pH in the dimerization system between 8.8 and 9.2, preferably 9.0, and a continuous cooling gradient of 1.5°C to 2.5°C / min is forcibly implemented, which helps to stabilize the dimerization process and inhibit the generation of melamine byproducts.

[0029] The crude dicyandiamide was dissolved, filtered, and recrystallized to obtain the finished dicyandiamide.

[0030] The solvent used to dissolve the crude dicyandiamide includes a mixture of water and ethanol, preferably with a water-to-ethanol volume ratio of 80:20. Filtration is performed using a submicron membrane, preferably a polyethersulfone (PES) membrane with a pore size of 0.22 μm or smaller, which helps remove submicron particulate impurities and some trace contaminants, further improving product purity.

[0031] In a preferred embodiment, the process for preparing the hydrogen-containing intermediate includes: continuously co-feeding urea, alkaline earth metal oxide, and scale inhibitor dopant into a dynamically sealed continuous rotary kiln for pyrolysis reaction, wherein the scale inhibitor dopant accounts for 0.1% to 5% of the weight of the alkaline earth metal oxide, preferably 0.6% to 1.8%. Further, the scale inhibitor dopant includes either silicon dioxide or titanium dioxide. Further, the scale inhibitor dopant is a mixture of silicon dioxide and titanium dioxide, with a mass ratio of silicon dioxide to titanium dioxide of 1:10 to 10:1. The silicon dioxide and titanium dioxide are preferably nanoscale products.

[0032] Introducing a scale inhibitor into the reaction system can alter the surface tension of the isocyanate melt, thereby improving the surface properties and rheological state of the intermediate melt. This reduces material adhesion and aggregation on the reactor wall, lowers the risk of scaling and clogging, and may even eliminate scale buildup on the reactor wall, improving the stability of continuous production. In a preferred embodiment, the mass ratio of silicon dioxide to titanium dioxide in the scale inhibitor is 1:10 to 10:1. Experiments show that without the addition of a scale inhibitor, equipment clogging and poor material discharge occur after one month of continuous operation, accompanied by severe localized overheating and material thermal degradation. The rotary kiln was initially classified as Grade III (severe scaling), impacting normal production. However, after adding a single scale inhibitor (silica or titanium dioxide), the scaling in the kiln decreased from Grade III (severe) to Grade II (moderate scaling), indicating that the addition of the scale inhibitor improved the scaling on the reactor wall. When a mixture of silica and titanium dioxide was used as the scale inhibitor, material adhesion to the reactor wall was significantly reduced, and the system maintained a relatively stable discharge state. No obvious thermal agglomeration or equipment blockage was observed, and after one month of continuous operation, the scaling level dropped to Grade I or even disappeared. In particular, when the silica to titanium dioxide mass ratio was 5:1, no scaling was observed on the inner wall of the reactor after one month of continuous operation, demonstrating that the scale inhibitor at this parameter could eliminate scaling on the reactor wall.

[0033] It is worth noting that the process temperature and process time involved in the above embodiments are all temperatures or times used in the experiment. Any reasonable adjustments made by those skilled in the art based on the process temperature and process time provided by the present invention, within the error range, should be included within the protection scope of the present invention.

[0034] The technical solution and effects of the present invention will be further illustrated below through specific embodiments.

[0035] It should be noted that in the embodiments of the present invention, all raw materials and reagents are commercially available and can be used without further purification.

[0036] The yield calculation formula and related parameters for dicyandiamide (DCDA) samples are explained below: (1) Core calculation formula The yield of dicyandiamide was determined using the following formula: Yield (%) = Actual product mass ÷ Theoretical product mass × 100% Actual product quality = Crude product quality × Purity (%) (2) Detailed definitions and parameters of each term in the formula To ensure accuracy, the terms in the formula are based on the following technical parameters: Theoretical product mass: This value is calculated based on stoichiometry and mainly refers to the amount of alkaline earth metal oxides (such as calcium oxide CaO) added.

[0037] Key ratio: When calculating the theoretical value, the present invention sets the optimal molar ratio of urea to alkaline earth metal oxide to be 2.05:1.00 to 2.15:1.00 (preferably 2.10:1.00).

[0038] Reaction pathway: The theoretical yield needs to consider the complete chemical transformation process from "urea pyrolysis to generate cyanide-containing intermediates" to "intermediate hydrolysis to generate monocyanamide", and then to "monocyanamide dimerization to generate dicyanamide".

[0039] Crude product quality: refers to the quality of unpurified dicyandiamide obtained directly after dimerization.

[0040] Purity (%): Obtained by purity testing of the obtained sample (e.g., HPLC determination).

[0041] 1. Experimental Example 1 A mixture of urea and CaO in the molar ratios shown in Table 1 was fed into a dynamically sealed rotary kiln. The pressure in the continuously sealed rotary kiln was maintained at 0.2 MPa by nitrogen purging. The mixture was passed sequentially through the first hot zone (200°C, 20 min), the second hot zone (320°C, 70 min), and the third hot zone (600°C, 30 min) to obtain a cyanide-containing intermediate. The cyanide-containing intermediate was hydrolyzed and then fed into a dimerization reactor for dimerization. During the dimerization process, the pH was maintained at 9.0 using a buffer system, and the temperature was lowered from 80°C to 20°C at a rate of 2.0°C / min to obtain crude dicyandiamide. The crude dicyandiamide was purified by filtration through a water-ethanol mixture with a volume ratio of 80:20 and a 0.22 μm polyethersulfone membrane to obtain the finished dicyandiamide.

[0042] 2. Comparative Example A mixture of urea and CaO in a molar ratio of 2.10:1.00 was fed into a dynamically sealed rotary kiln. The pressure in the continuously sealed rotary kiln was maintained at 0.2 MPa by purging with nitrogen. The mixture was heated to 320°C and held for 70 min, then heated to 600°C and held for 30 min, yielding a cyanide-containing intermediate. The cyanide-containing intermediate was hydrolyzed and fed into a dimerization reactor for dimerization. During dimerization, a buffer system was used to maintain the pH at 9.0, and the temperature was lowered from 80°C to 20°C at a rate of 2.0°C / min to obtain crude dicyandiamide. The crude dicyandiamide was purified by filtration through a water-ethanol mixture with a volume ratio of 80:20 and a 0.22 μm polyethersulfone membrane to obtain the finished dicyandiamide.

[0043] The purity of each dicyandiamide sample was tested, and its yield and melamine impurity content were calculated. The results are shown in Table 1.

[0044] Table 1. Yield and purity of each sample

[0045] As shown in Table 1, with other process conditions unchanged, changing the molar ratio of urea to CaO significantly affects the melamine impurity content in the product. In Sample 1, when the molar ratio of urea to CaO was 1.90:1.00, insufficient urea led to incomplete CaO conversion, and excessive unreacted alkaline residues affected the pH in the buffer system, increasing the difficulty of maintaining pH, and the melamine impurity content was relatively high. In Sample 2, when the molar ratio of urea to CaO was 2.10:1.00, the melamine impurity content was <0.01%, the heavy metal content was 2 g / 100 g, and the purity of the dicyandiamide sample reached 99.88% while the yield remained at a high level. In Sample 3, when the molar ratio of urea to CaO was 2.30:1.00, excessive urea decomposition led to uncontrollable ammonia pressure peaks in the dynamically sealed continuous rotary kiln, posing a risk of seal blowout, and resulting in complex and excessively high impurity composition in the final product, especially excessively high melamine content. A urea to CaO molar ratio below 2.05:1.00 will lead to incomplete CaO conversion and alkaline residue; a ratio above 2.15:1.00 will cause ammonia pressure peaks and increase impurities such as melamine.

[0046] Meanwhile, the setting of different heat zones also significantly affects the content of melamine impurities in the product. The comparative sample, which was reacted using two heat zones, had a higher content of melamine impurities. It is evident that a suitable molar ratio of urea to alkaline earth metal oxides and appropriate heat zone settings work together to have a positive synergistic effect on reducing the impurity content and improving the purity of dicyandiamide products.

[0047] 3. Experimental Example 2 The preparation method of dicyandiamide is the same as that of sample 2 in Experimental Example 1, except that the pressure in the dynamic sealed continuous rotary kiln is maintained at the pressure shown in Table 2 by nitrogen purging.

[0048] The purity of each dicyandiamide sample was tested, and its yield and melamine impurity content were calculated. The results are shown in Table 2.

[0049] Table 2. Yields and purity of each sample in Experiment Example 2

[0050] As can be seen from Table 2, changing the pressure in the rotary kiln has a significant impact on the dicyandiamide yield while keeping other process conditions constant. Sample 4 was produced under standard 0 MPa (atmospheric pressure), meaning the rotary kiln was unsealed. A large amount of HNCO gas volatilized and escaped, causing severe scaling and clogging of the reactor. The final product, dicyandiamide, had a low yield of only 68.0%, and the required purity (>99.5%) for API grade DCDA was not met. Sample 5, produced under a positive pressure of 0.1 MPa in the rotary kiln, initially suppressed HNCO gas volatilization, resulting in a dicyandiamide yield higher than Sample 4, exceeding 80%. Sample 2, produced under a rotary kiln pressure of 0.2 MPa, achieved a dicyandiamide yield as high as 93.5%. As the pressure in the rotary kiln increased (Sample 6, produced at 0.3 MPa), the dicyandiamide yield decreased compared to Sample 2, but still remained above 80%. These data demonstrate that a positive pressure environment plays a crucial role in suppressing the volatilization of the intermediate isocyanate (HNCO) and improving the dicyandiamide yield. Meanwhile, all samples produced under pressure of 0.1-0.3 MPa maintained a purity of 99.88%, and the melamine impurity content was extremely low (<0.01%), fully complying with pharmaceutical-grade API standards.

[0051] 4. Experimental Example 3 The preparation method of dicyandiamide is the same as that of sample 2 in Experiment 1, except that a scale inhibitor dopant accounting for 1.2% of the CaO mass is added to the raw material. The types and amounts of scale inhibitor dopant are shown in Table 4. Meanwhile, the preparation method of sample 2 is used as a control group.

[0052] After one month of system operation, the scaling condition on the rotary kiln wall was inspected using an ultrasonic thickness gauge combined with visual inspection and photography. The scaling condition was classified into four levels based on the coverage area and thickness of the scale layer, as follows: Table 3. Evaluation Table of Scaling Level on Rotary Kiln Inner Wall

[0053] Table 4. Detection data of each sample in Experiment Example 3 and scaling level of the rotary kiln inner wall.

[0054] Please refer to the table above. Samples 7 to 11 were prepared by adding scale inhibitors to the raw materials for dicyandiamide preparation. Compared to Sample 2, which did not contain scale inhibitors, the addition of scale inhibitors did not adversely affect the yield and purity of dicyandiamide, and the content of melamine impurities remained at an extremely low level. However, during the preparation of Sample 2, the isocyanate-containing intermediates exhibited a strong tendency to adhere and aggregate under high-temperature conditions (i.e., thermal agglomeration). Hard scale rapidly formed on the reactor wall, and after one month of continuous operation, equipment blockage and poor discharge occurred, accompanied by severe local overheating and material thermal degradation. The rotary kiln's scaling level was Class III severe scaling. Long-term operation would block the reactor, not only affecting normal production but also increasing equipment maintenance costs and service life.

[0055] Samples 7 and 8 represent the cases where a single scale inhibitor was added. It can be seen that, under the action of the scale inhibitor, the scaling condition inside the rotary kiln decreased from the original severe (Level III) scaling to moderate (Level II) scaling. Although the scaling condition was improved compared to Sample 2, it still could not meet the expectations for normal production. Samples 9 to 11 represent the cases where a mixture of silica and titanium dioxide was used as the scale inhibitor. During continuous operation, the scale inhibitor helped improve the surface properties and rheological state of the intermediate melt, thereby reducing the agglomeration and adhesion of the intermediate. The adhesion of materials to the reactor wall was significantly reduced, and the system was able to maintain a relatively stable discharge state. No obvious thermal agglomeration or equipment blockage was observed. The overall scaling condition of the rotary kiln inner wall was good, especially Sample 10, with a silica to titanium dioxide mass ratio of 5:1. The system showed no scaling after one month of operation, ensuring normal production, while reducing equipment maintenance costs and extending service life.

[0056] The above embodiments merely illustrate several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

Claims

1. A method for preparing pharmaceutical-grade dicyandiamide by urea pyrolysis, characterized in that, This includes the process of preparing a cyanide-containing intermediate and the process of preparing dicyandiamide from the cyanide-containing intermediate, wherein the process of preparing the cyanide-containing intermediate includes: Urea and alkaline earth metal oxide are continuously co-fed into a dynamic sealed reaction system at a molar ratio of 2.10:1.00, sequentially passing through a first hot zone (temperature 180°C to 220°C, residence time 15 to 30 min), a second hot zone (temperature 300°C to 350°C, residence time 45 to 90 min), and a third hot zone (temperature 580°C to 620°C, residence time 20 to 40 min) to obtain a cyanide-containing intermediate. The alkaline earth metal oxide is calcium oxide. The pressure in the dynamic sealed reaction system is 0.1 to 0.3 MPa.

2. The method for preparing pharmaceutical-grade dicyandiamide by urea pyrolysis as described in claim 1, characterized in that, The process of preparing dicyandiamide from a cyanide-containing intermediate includes the following steps: The cyanide-containing intermediate was hydrolyzed to obtain monocyanamide; The monocyanamide was subjected to a dimerization reaction to obtain crude dicyanamide; The crude dicyandiamide was dissolved, filtered, and recrystallized to obtain the finished dicyandiamide.

3. The method for preparing pharmaceutical-grade dicyandiamide by urea pyrolysis as described in claim 2, characterized in that, The dimerization process uses a buffer system to maintain the pH of the dimerization reaction system between 8.8 and 9.2 and forces a continuous cooling gradient of 1.5°C to 2.5°C / min.

4. The method for preparing pharmaceutical-grade dicyandiamide by urea pyrolysis as described in claim 3, characterized in that, The filtration process uses a polyethersulfone membrane with a pore size ≤ 0.22 μm for purification.

5. The method for preparing pharmaceutical-grade dicyandiamide by urea pyrolysis as described in claim 1, characterized in that, The process for preparing the cyanide-containing intermediate includes: continuously feeding urea, alkaline earth metal oxide and scale inhibitor into a dynamic sealed continuous rotary kiln for pyrolysis reaction, wherein the scale inhibitor accounts for 0.1% to 5% of the weight of the alkaline earth metal oxide.

6. The method for preparing pharmaceutical-grade dicyandiamide by urea pyrolysis as described in claim 5, characterized in that, The scale inhibitor dopant includes at least one of silicon dioxide and titanium dioxide.

7. The method for preparing pharmaceutical-grade dicyandiamide by urea pyrolysis as described in claim 6, characterized in that, The scale inhibitor is a mixture of silicon dioxide and titanium dioxide, wherein the mass ratio of silicon dioxide to titanium dioxide is 1:10 to 10:1.

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