A method for preparing low-cost and high-quality cyanoimide-1,3-thiazolidine

Abstract

The invention belongs to the technical field of chemical organic synthesis, and relates to a method for preparing a low-cost high-quality cyano-1,3-thiazolidine. The present invention forms a "micro-nano" aqueous suspension of low-content dimethyl cyano-imide before the reaction by using a homogenization technique, so that the solid-liquid interface of the reaction process is greatly increased, and the reaction is carried out at a microscale, so that the reaction is more thorough, and impurities are more easily diffused into the mother liquor rather than into the product. The preparation method's process is simple and easy, the raw materials are cheap and easy to obtain, the reaction conditions are mild, and it is suitable for large-scale production.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical organic synthesis, and particularly relates to a method for preparing low-cost and high-quality cyanoimino-1,3-thiazolidine. Background Art

[0002] Cyanimido-1,3-thiazolidine is an important heterocyclic organic synthetic molecular building block and an important structural unit for the preparation of crop protection active ingredients (such as the insecticide thiacloprid) and pharmaceutical active ingredients, as well as optoelectronic materials.

[0003] At present, there is only one process route for the industrial production of cyano-1,3-thiazolidine, as described in the Chinese patent publications CN101801943A, CN1487926A and CN102399216A. All three use a process route of cyclizing N-cyano-S,S-dimethyl dithiocarbonate with cysteamine hydrochloride under alkaline conditions to generate thiazolidine. The process route is as follows:

[0004]

[0005] In this process, high-purity cysteamine hydrochloride and dimethyl cyanamide are used as the main raw materials. The Chinese patent publication number CN1487926A emphasizes the use of 99.5% cysteamine hydrochloride and dimethyl cyanamide; the Chinese patent publication number CN101801943A does not emphasize the purity and content of the raw materials, but based on the feed mass and molar amount, it can be inferred that the raw materials used are high-content raw materials; the Chinese patent publication number CN102399216A also mentions the use of chloroform extraction to obtain high-quality dimethyl cyanamide raw materials for the next step of synthesis.

[0006] The commercially available bulk cysteamine hydrochloride has a mass content of only 95%. The 99% mass content of cysteamine hydrochloride products need to be customized and the price is much higher than the 95% mass content of cysteamine hydrochloride products. The main specification of the commercially available dimethyl cyanamide products is a crude product with a mass content of 90%. To achieve the 99% specification, recrystallization and purification are required, resulting in a significant increase in the cost and selling price of high-content dimethyl cyanamide products; at the same time, since dimethyl cyanamide is a highly allergenic material, during the recrystallization process, especially when it involves the processing of powder materials, it is very easy to cause employees to be allergic due to dust inhalation or skin contact, and cause serious occupational diseases. In addition, if the allergy to dimethyl cyanamide is not treated in time, it can be fatal.

[0007] Therefore, there is an urgent need to develop a method for preparing cyanimido-1,3-thiazolidine with low cost and safety for workers. Summary of the invention

[0008] In view of the technical problems existing in the current production process, the present invention provides a low-cost and high-quality preparation method of cyanimido-1,3-thiazolidine. The preparation method has a simple and easy process, cheap and readily available raw materials, mild reaction conditions, and is suitable for large-scale production.

[0009] To achieve the above purpose, the present invention adopts the following technical solutions.

[0010] A method for preparing low-cost and high-quality cyanoimido-1,3-thiazolidine comprises the following steps:

[0011] Step 1, adding process water and 90% crude dimethyl cyanamide product by mass into a homogenizing reactor at one time, turning on a homogenizing pump to homogenize at a certain temperature until the reaction system is visually uniform and there are no particles visible to the naked eye. After the homogenization is completed, keep stirring for standby;

[0012] Step 2: Add process water and inorganic base into the cyclization reactor in sequence at room temperature, stir until fully dissolved, add 95% by weight cysteamine hydrochloride, and stir fully to fully release cysteamine;

[0013] Step 3, cooling the material in the cyclization reactor to the reaction temperature, opening the vacuum system, and dripping the suspension in the homogenizing reactor in step 1 at a controlled temperature, controlling the dripping speed to ensure that the vacuum degree is not less than 0.05 MPa; closing the dripping, keeping warm for 1 hour, and starting sampling to track the reaction of the raw materials until the reaction of the raw materials is complete; adding hydrochloric acid to adjust the pH value of the system to 6-7, filtering or centrifuging, washing the filter cake with process water, and drying to obtain the target product cyanimido-1,3-thiazolidine.

[0014] Furthermore, in step 1, the mass ratio of process water to 90% crude dimethyl cyanamide is 2.0-6.0:1, preferably 3-5:1, and particularly preferably 4:1.

[0015] Furthermore, in step 1, the temperature is 5-50°C, preferably 15-25°C; and the homogenization time is 0.5-1.5h.

[0016] Furthermore, in step 1, the homogenization method is in-kettle homogenization (a homogenizer is installed in the kettle) or external circulation homogenization (circulation through a pipeline homogenization pump).

[0017] Furthermore, in step 2, the inorganic base is one of metal hydroxide, metal carbonate or bicarbonate; preferably metal hydroxide, particularly preferably sodium hydroxide.

[0018] Furthermore, in step 2, the molar ratio of 95% by mass of cysteamine hydrochloride to 90% by mass of dimethyl cyanimidate in step 1 is 1.0-1.2:1, preferably 1.05-1.10:1, and particularly preferably 1:1.

[0019] Furthermore, in step 2, the mass ratio of process water to 95% by mass cysteamine hydrochloride is 2.0-4.0:1, preferably 3.0:1.

[0020] Furthermore, in step 2, the molar ratio of the inorganic base to 95% by mass of cysteamine hydrochloride is 1.0-1.2, preferably 1.0-1.1.

[0021] Furthermore, in step 2, the stirring time is 1-2h.

[0022] Furthermore, in step 3, the reaction temperature is 5-20°C, preferably 10-15°C.

[0023] Furthermore, step 1 and step 2 can be carried out in either a batch or continuous reaction manner.

[0024] Compared with the prior art, the beneficial effects of the present invention are as follows.

[0025] (1) The present invention analyzes the mechanism and finds that the reaction is a solid-liquid heterogeneous reaction process. The raw material dimethyl cyanimide is insoluble in water, and the product cyanimide-1,3-thiazolidine is also insoluble in water. The traditional reaction process easily contains impurities in the raw material dimethyl cyanimide or even unreacted dimethyl cyanimide raw material in the product, resulting in poor product quality and low content. The present invention uses homogenization technology to form dimethyl cyanimide into a "micro-nano-scale" aqueous suspension before the reaction, so that the solid-liquid interface in the reaction process is greatly increased, and the reaction is carried out at a microscale, so that the reaction is more thorough and impurities are more likely to diffuse into the mother liquor rather than into the product.

[0026] (2) The production cost is greatly reduced: The product of the present invention uses low-content dimethyl cyanimide and cysteamine hydrochloride as raw materials, which significantly reduces the cost. Only the methyl cyanimide needs to be pretreated to achieve the preparation of high-quality cyanimide-1,3-thiazolidine, and the product has good quality and high yield.

[0027] (3) Reduced safety and environmental risks: The raw material dimethyl cyanamide is a highly allergenic substance. This project avoids the use of high-content and fine powdered dimethyl cyanamide refined products and uses granular crude products instead, which greatly reduces safety, environmental protection and occupational health risks. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 Diagram of homogenization operation inside the reactor.

[0029] Figure 2 Reactor external circulation homogenization operation diagram. DETAILED DESCRIPTION

[0030] The following is an explanation of the embodiments of the present invention by specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The implementation conditions used in the embodiments can be further adjusted according to the different requirements of specific use, and the implementation conditions not specified are the conventional conditions of the industry.

[0031] A method for preparing low-cost and high-quality cyanoimido-1,3-thiazolidine comprises the following steps:

[0032] Step 1, adding process water and 90% crude dimethyl cyanamide product by mass into a homogenizing reactor at one time, turning on a homogenizing pump to homogenize at a certain temperature until the reaction system is visually uniform and there are no particles visible to the naked eye. After the homogenization is completed, keep stirring for standby;

[0033] Step 2: Add process water and inorganic base into the cyclization reactor in sequence at room temperature, stir until fully dissolved, add 95% by weight cysteamine hydrochloride, and stir fully to fully release cysteamine;

[0034] Step 3, cooling the material in the cyclization reactor to the reaction temperature, opening the vacuum system, and dripping the suspension in the homogenizing reactor in step 1 at a controlled temperature, controlling the dripping speed to ensure that the vacuum degree is not less than 0.05 MPa; closing the dripping, keeping warm for 1 hour, and starting sampling to track the reaction of the raw materials until the reaction of the raw materials is complete; adding hydrochloric acid to adjust the pH value of the system to 6-7, filtering or centrifuging, washing the filter cake with process water, and drying to obtain the target product cyanimido-1,3-thiazolidine.

[0035] Furthermore, in step 1, the mass ratio of process water to 90% crude dimethyl cyanamide is 2.0-6.0:1, preferably 3-5:1, and particularly preferably 4:1.

[0036] Furthermore, in step 1, the temperature is 5-50°C, preferably 15-25°C; and the homogenization time is 0.5-1.5h.

[0037] Furthermore, in step 1, the homogenization method is in-kettle homogenization (a homogenizer is installed in the kettle) or external circulation homogenization (circulation through a pipeline homogenization pump).

[0038] Furthermore, in step 1, the homogenizing pump is any type of homogenizer or homogenizing pump commonly sold on the market.

[0039] Furthermore, in step 2, the inorganic base is one of metal hydroxide, metal carbonate or bicarbonate; preferably metal hydroxide, particularly preferably sodium hydroxide.

[0040] Furthermore, in step 2, the molar ratio of 95% by mass of cysteamine hydrochloride to 90% by mass of dimethyl cyanimidate in step 1 is 1.0-1.2:1, preferably 1.05-1.10:1, and particularly preferably 1:1.

[0041] Furthermore, in step 2, the mass ratio of process water to 95% by mass cysteamine hydrochloride is 2.0-4.0:1, preferably 3.0:1.

[0042] Furthermore, in step 2, the molar ratio of the inorganic base to 95% by mass of cysteamine hydrochloride is 1.0-1.2, preferably 1.0-1.1.

[0043] Furthermore, in step 2, the stirring time is 1-2h.

[0044] Furthermore, in step 3, the reaction temperature is 5-20°C, preferably 10-15°C.

[0045] Furthermore, step 1 and step 2 can be carried out in either a batch or continuous reaction manner.

[0046] The present invention is further described below by way of examples, but the scope of the present invention is not limited thereto.

[0047] Embodiment 1:

[0048] 1. Add 1230kg of process water and 410kg of 90% crude dimethyl cyanamide into a 3000L homogenizing reactor at once, and control the temperature at 20℃. Figure 2 As shown, the external circulation homogenizing pump is turned on to perform external circulation homogenization for 1.0 h, until the reaction system appears to be a uniform slurry with no visible particles; after the homogenization is completed, the stirring state is maintained for standby use.

[0049] 2. At room temperature, add 1210 kg of process water and 110 kg of sodium hydroxide into a 5000 L cyclization reactor in sequence and stir until fully dissolved; add 303 kg of 95% cysteamine hydrochloride and stir for 1.5 hours.

[0050] 3. Cool the material in the cyclization reactor to 5°C, open the vacuum system, and drip the suspension in the homogenization reactor at a controlled temperature. Control the dripping speed to ensure that the vacuum degree is not less than 0.05MPa. Close the dripping, keep warm for 1h, and start sampling to track the raw material reaction until the raw material reaction is complete.

[0051] 4. Control the temperature and add hydrochloric acid to adjust the pH value of the system to 6.5, centrifuge, wash the filter cake with 500L of process water, and dry to obtain 301kg of cyanimido-1,3-thiazolidine. The purity was 99.1% by HPLC, the content was 98.0%, and the yield was 93%.

[0052] Embodiment 2:

[0053] 1. Add 1640 kg of process water and 410 kg of 90% crude dimethyl cyanamide into the homogenizing reactor at one time, and control the temperature at 5 °C. Figure 2 As shown, the external circulation homogenizing pump is turned on to perform external circulation homogenization for 1.0 h, until the reaction system appears to be a uniform slurry with no visible particles; after the homogenization is completed, the stirring state is maintained for standby use.

[0054] 2. At room temperature, add 606 kg of process water and 110 kg of sodium hydroxide into a 5000 L cyclization reactor in sequence and stir until fully dissolved; add 303 kg of 95% cysteamine hydrochloride and stir for 2 hours.

[0055] 3. Cool the material in the cyclization reactor to 20°C, open the vacuum system, and add the suspension in the homogenization reactor dropwise under temperature control. Control the dropping speed to ensure that the vacuum degree is not less than 0.05Mpa; close the dripping, keep warm for 1h, and start sampling to track the raw material reaction until the raw material reaction is completed.

[0056] 4. Control the temperature and add hydrochloric acid to adjust the pH value of the system to 6, centrifuge, wash the filter cake with 500L of process water, and dry to obtain 298kg of cyanimido-1,3-thiazolidine. The purity determined by HPLC is 99.2%, the content is 98.2%, and the yield is 91%.

[0057] Embodiment 3:

[0058] 1. Add 1230 kg of process water and 410 kg of 90% crude dimethyl cyanamide into the homogenizing reactor at one time, and control the temperature at 10 °C. Figure 1 As shown, the homogenizer in the reactor was turned on to homogenize for 1.0 h until the reaction system appeared to be a uniform slurry with no visible particles; after the homogenization was completed, the stirring state was maintained for standby use.

[0059] 2. At room temperature, add 909 kg of process water and 348 kg of potassium carbonate to a 5000 L cyclization reactor in sequence and stir until fully dissolved; add 303 kg of 95% cysteamine hydrochloride and stir for 1.5 h.

[0060] 3. Cool the material in the cyclization reactor to 10°C, open the vacuum system, and add the suspension in the homogenization reactor dropwise at a controlled temperature. Control the dropping speed to ensure that the vacuum degree is not less than 0.05Mpa; close the dripping, keep warm for 1h, and start sampling to track the raw material reaction until the raw material reaction is completed.

[0061] 4. Control the temperature and add hydrochloric acid to adjust the pH value of the system to 6-7, centrifuge, wash the filter cake with 500L of process water, and dry to obtain 295kg of cyanimido-1,3-thiazolidine. The purity was 99.0% by HPLC, the content was 98.1%, and the yield was 91%.

[0062] Embodiment 4:

[0063] 1. Add 2050 kg of process water and 410 kg of 90% crude dimethyl cyanamide into the homogenizing reactor at one time, and control the temperature at 40 °C. Figure 1 As shown, the homogenizer in the reactor was turned on to homogenize for 1.5 hours until the reaction system appeared to be a uniform slurry with no visible particles; after the homogenization was completed, the stirring state was maintained for standby use.

[0064] 2. At room temperature, add 909 kg of process water and 252 kg of sodium bicarbonate to a 5000 L cyclization reactor in sequence and stir until fully dissolved; add 318 kg of 95% cysteamine hydrochloride and stir for 1-2 hours.

[0065] 3. Cool the material in the cyclization reactor to 15°C, open the vacuum system, and add the suspension in the homogenization reactor dropwise at a controlled temperature. Control the dropping speed to ensure that the vacuum degree is not less than 0.05Mpa; close the dripping, keep warm for 1h, and start sampling to track the raw material reaction until the raw material reaction is completed.

[0066] 4. Control the temperature and add hydrochloric acid to adjust the pH value of the system to 6-7, centrifuge, wash the filter cake with 500L of process water, and dry to obtain 295kg of cyanimido-1,3-thiazolidine. The purity was 98.6% by HPLC, the content was 98.0%, and the yield was 91.5%.

[0067] Comparative Example 1:

[0068] Add 1500kg of deionized water and 265kg of sodium carbonate to a 3000L reactor, stir until fully dissolved, add 303kg of cysteamine hydrochloride (95%) into the reactor and stir until fully mixed, cool to 10 degrees, add 410kg of dimethyl cyanoimidate (90% commercially available, solid particles), and keep warm for 5 hours; during the reaction, keep vacuuming to extract the methyl mercaptan generated by the reaction to the waste gas treatment device. After the reaction is completed, add a certain amount of hydrochloric acid to adjust the pH to neutral. Filter to obtain 295kg (dry) cyanoimidate-1,3-thiazolidine, with a conversion rate of 96.5%, unreacted dimethyl cyanoimidate 3.5%, HPLC determination of purity of 95.5%, content of 93.4%, and yield of 86%.

[0069] The preparation method of this comparative example refers to CN101801943A, but dimethyl cyanimidate and cysteamine hydrochloride are consistent with the example.

[0070] Comparative Example 2:

[0071] Add 1500kg of deionized water and 112kg of sodium hydroxide to a 3000L reactor, stir until fully dissolved, add 303kg of cysteamine hydrochloride (95%) into the reactor and stir until fully mixed, cool to 0 degrees, add 408kg of dimethyl cyanoimidate (90% commercially available, solid particles), keep warm at 0-5℃ for 2h. Raise the temperature by 20℃, add a certain amount of hydrochloric acid to adjust the pH to 4.0, heat to 40℃ and mature for 2h. Cool to 20℃ for crystallization, filter and wash the filter cake to obtain 288kg (dry) cyanoimido-1,3-thiazolidine, HPLC determination of purity 94.5%, content 92.7%, yield 83%.

[0072] The preparation method of this comparative example refers to CN1487926A, but dimethyl cyanimidate and cysteamine hydrochloride are consistent with the example.

Claims

1. A method for preparing a low-cost and high-quality cyano-1,3-thiazolidine, characterized in that: The following steps are involved: Step 1, adding process water and 90% crude dimethyl cyanamide into a homogenizing reactor at once, turning on the homogenizing pump to homogenize at a temperature of 5-50° C. for 0.5-1.5 hours, until the reaction system is visually uniform and there are no particles visible to the naked eye. After the homogenization is completed, keep stirring for standby; Step 2: adding process water and inorganic base to the cyclization reactor in sequence at room temperature, stirring until fully dissolved, adding 95% by weight of cysteamine hydrochloride, and stirring fully to fully free the cysteamine; the inorganic base is one of a metal hydroxide, a metal carbonate or a bicarbonate, and the molar ratio of the 95% by weight of cysteamine hydrochloride to the 90% by weight of dimethyl cyanamide in step 1 is 1.0-1.2:1; Step 3, cooling the material in the cyclization reactor to the reaction temperature, the reaction temperature is 5-20°C, opening the vacuum system, controlling the temperature to drip the suspension in the homogenizing reactor in step 1, and controlling the dripping speed to ensure that the vacuum degree is not less than 0.05Mpa; closing the dripping, keeping warm for 1h, starting sampling to track the reaction of the raw materials until the reaction of the raw materials is complete; adding hydrochloric acid to adjust the pH value of the system to 6-7, filtering or centrifuging, washing the filter cake with process water, and drying to obtain the target product cyanimido-1,3-thiazolidine.

2. The method for preparing low-cost and high-quality cyanoimido-1,3-thiazolidine according to claim 1, characterized in that: In the step 1, the mass ratio of process water to crude dimethyl cyanamide having a mass content of 90% is 2.0-6.0:

1.

3. The method for preparing low-cost and high-quality cyanoimido-1,3-thiazolidine according to claim 1, characterized in that: In the step 1, the homogenization method is in-tank homogenization or external circulation homogenization.

4. The method for preparing low-cost and high-quality cyanoimido-1,3-thiazolidine according to claim 1, characterized in that: In the step 2, the mass ratio of process water to cysteamine hydrochloride having a mass content of 95% is 2.0-4.0:

1.

5. The method for preparing low-cost and high-quality cyanoimido-1,3-thiazolidine according to claim 1, characterized in that: In the step 2, the molar ratio of the inorganic base to 95% by mass of cysteamine hydrochloride is 1.0-1.

2.

6. The method for preparing low-cost and high-quality cyanoimido-1,3-thiazolidine according to claim 1, characterized in that: In the step 2, the stirring time is 1-2h.

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