WO2021179921A2 - 一种采用连续釜式反应器制备咪唑的方法 - Google Patents
一种采用连续釜式反应器制备咪唑的方法 Download PDFInfo
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- the invention belongs to the technical field of organic compound synthesis, and specifically relates to a method for preparing imidazole by adopting a continuous tank reactor.
- Imidazole is mainly used as raw materials for pharmaceuticals and pesticides. It is one of the main raw materials for azoles, econazoles, ketoconazoles, clotrimazoles and other drugs. It is also widely used as a preservative for fruits and vegetables and as a ring Oxygen resin curing agent, the amount of which accounts for more than 90%, is a very important organic synthesis intermediate.
- the domestic and foreign industrial production methods of imidazole mainly use ⁇ -dicarbonyl compound (glyoxal), ammonia and aldehyde as raw materials, and form imidazole ring through condensation reaction.
- the reaction is usually carried out in an indirect tank reactor.
- the method of dripping is adopted: under continuous stirring, the mixed solution of glyoxal and formaldehyde is slowly dripped into the ammonia source solution for several hours or longer, and the temperature is continued after the dripping is completed. It takes dozens of hours to complete the reaction; the traditional batch process has the disadvantages of high production cost, many by-products and low safety.
- Patent CN109422693A discloses a method for continuously preparing imidazole using microreaction technology, which uses continuous flow of microchannel reaction to prepare imidazole, but it is easy to block the microchannel tube because the imidazole reaction will produce some solid insoluble particles; secondly, the patented reaction temperature A large amount of by-products are produced above 100°C, which is not conducive to the subsequent concentration and rectification of imidazole; the second patent reaction is a pressure reaction which is not conducive to safe production.
- the invention provides a method for continuously synthesizing imidazole by adopting a continuous tank reactor.
- the present invention proposes a simple and efficient continuous tank reactor, and provides a continuous imidazole preparation with high yield, few by-products, simple equipment operation and high safety method.
- Feeding start the continuous tank reactor and stir, control the flow rate of the first feed liquid to be 1mL/min ⁇ 100mL/min and control the flow rate of the second feed liquid to be 1mL/min ⁇ 300mL/min and enter the reactor at the same time, so that It is fully reacted, and the residence time of the material in the reactor is controlled to be 5-10h;
- step S3 The reaction liquid obtained in step S2 flows into the concentration tank through the overflow of the continuous tank reactor, and the reaction liquid is collected and concentrated and rectified to obtain the imidazole product.
- the second feed liquid further includes a catalyst
- the catalyst is one or more of ammonium chloride, ammonium acetate, ammonium carbonate, ammonium bicarbonate, ammonium sulfate, ammonium phosphate, or ammonium nitrate.
- the addition of catalyst can significantly increase the reaction rate.
- ammonia source is preferably ammonia water, and can also be ammonium acetate, ammonium bicarbonate, ammonium carbonate, ammonium chloride or ammonium sulfate.
- the mass fractions of the formaldehyde solution and the glyoxal solution are both 10%-50%, preferably the formaldehyde concentration is 37%, preferably the glyoxal concentration is 40%, and the molar ratio of formaldehyde and glyoxal is The ratio is 1:1 to 1:2, the mass fraction of the aqueous ammonia solution is 10% to 25%, and the molar ratio of the catalyst to the ammonia water is 0:10 to 1:40.
- reaction temperature in the step S2 is controlled at 40-90°C.
- the stirring speed in the step S2 is 50-300 r/min.
- a forced pump circulation device is connected to the outside of the continuous tank reactor, and the mass transfer and heat transfer of the reaction medium are enhanced by the externally reinforced pump circulation device, so as to better promote the progress of the reaction.
- the continuous tank reactor has an unprecedented improvement in reaction efficiency.
- the traditional tank-type batch reaction leads to too long reaction time (about 30-35 hours) without in-depth study of the imidazole reaction kinetics. Therefore, by optimizing the reaction, it is found that the residence time of the reaction is only 5-10 hours, which increases the efficiency several times.
- the continuous tank reactor used in the reaction adopts the reactor commonly used in the prior art, and mainly includes a reaction sleeve, a heat exchange interlayer, a constant speed stirring device, an external heat exchange tube, a cooling and heating integrated device, and a reaction sleeve setting Two feed inlets, two heat exchange ports and one overflow outlet, and the heat exchange interlayer is connected with the integrated cooling and heating device.
- the present invention provides a new process for preparing imidazole by a continuous method. Compared with the existing batch reaction technology, it has the following significant advantages:
- the present invention adopts a continuous tank reactor to prepare imidazole, which can effectively reduce the exothermic phenomenon in the reaction process by accurately controlling the flow rate and residence time, improve safety performance, and improve reaction efficiency.
- reaction technology of the present invention for preparing imidazole in the continuous tank reactor enables continuous production of imidazole, which not only reduces or even avoids the content of by-product urotropine, but also has stable product quality, yield and production efficiency (Yield increased by 7-10%, purity>99%) is improved, thus laying the foundation for the industrialization of technology.
- S2 feed Set the first feed liquid mixed aldehyde solution according to the feed flow rate of 11ml/min through the peristaltic pump, and set the second feed liquid ammonia catalyst solution at the feed flow rate of 15ml/min to set the reaction
- the temperature is 55°C
- the stirring speed is 100r/min
- the residence time of the material is controlled to be 8.5h to make it fully react.
- step S3 reaction post-processing: the reaction liquid of step S2 flows into the concentration kettle through the overflow, and the reaction liquid is collected and concentrated and rectified to obtain the imidazole product. After detection and analysis by gas chromatography, the yield of imidazole is calculated to be 80% and the purity is >99%.
- S2 feed Set the first feed liquid mixed aldehyde solution according to the feed flow rate of 8ml/min through the peristaltic pump, and set the second feed liquid ammonia and catalyst solution at the feed flow rate of 10ml/min.
- the reaction temperature is 65°C
- the stirring speed is 80r/min
- the residence time of the material is controlled for 6h to make it fully react.
- reaction liquid flows into the concentration kettle through the overflow, and the reaction liquid is collected and rectified to obtain the imidazole product.
- the yield of imidazole is calculated to be 88%, and the purity is >99%.
- S2 Feeding mode Set the first feed liquid mixed aldehyde solution at a feed flow rate of 9ml/min through a peristaltic pump, and set the second feed liquid ammonia and catalyst solution at a feed flow rate of 12ml/min.
- the reaction temperature is set to 85°C
- the stirring speed is 100r/min
- the residence time of the material is controlled to be 5h to make it fully react.
- reaction liquid flows into the concentration kettle through the overflow, and the reaction liquid is collected and concentrated and rectified to obtain the imidazole product. After detection and analysis by gas chromatography, the yield of the imidazole is calculated to be 81% and the purity is >99%.
- S2 feed Set the first feed liquid mixed aldehyde solution according to the feed flow rate of 10ml/min through the peristaltic pump, and set the second feed liquid ammonia and catalyst solution at the feed flow rate of 15ml/min.
- the reaction temperature is 75°C
- the stirring speed is 80r/min
- the residence time of the material is controlled for 10h to make it fully react.
- reaction liquid flows into the concentration kettle through the overflow, and the reaction liquid is collected and concentrated and rectified to obtain imidazole products. After gas chromatography detection and analysis, the yield of imidazole is calculated to be 84%, and the purity is >99%.
- S2 feed Set the first feed liquid mixed aldehyde solution at a feed flow rate of 15ml/min through a peristaltic pump, and set the second feed liquid ammonia and catalyst solution at a feed flow rate of 22ml/min.
- the reaction temperature is 70°C
- the stirring speed is 60r/min
- the residence time of the material is controlled to be 9.5h to make it fully react.
- reaction liquid flows into the concentration kettle through the overflow, and the reaction liquid is collected and concentrated and rectified to obtain the imidazole product.
- the yield of imidazole is calculated to be 85%, and the purity is >99%.
- the method of preparing imidazole by continuous kettle is compared with the traditional batch method for preparing imidazole using parallel conditions. It is found that the yield of imidazole products prepared by continuous kettle is higher than that of imidazole prepared by batch method under the same conditions, and the yields are both Correspondingly, Example 1 and Comparative Example 1 did not add a catalyst, and the continuous production mode increased the yield by 8% compared with the batch production mode. Although the catalyst was added in Examples 2-5 and Comparative Example 2-5, the yield It also increased by 7-10%, which is extremely important for industrial production. To the inventor’s surprise, not only the yield has been greatly improved, but the quality of the product has also been improved.
- the content of imidazole prepared by continuous kettle exceeds 99%.
- the inventor believes that it is possible The reason is that in traditional reactions, a large amount of materials participate in the reaction and generate a large amount of heat, which makes the unit time exothermic violently, provides an environment for side reactions, and reduces the yield; while the continuous tank reactor can realize the material per unit time. Effective mixing and effective heat transfer reduce or even avoid side reactions, thereby improving yield and quality.
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Description
本发明属于有机化合物合成技术领域，具体涉及一种采用连续釜式反应器制备咪唑的方法。
咪唑，主要用作医药原料和农药原料，是唑类、益康唑类、酮康唑类、克霉唑类等药物的主要原料之一，另外还广泛的用于果蔬防腐剂，用作环氧树脂固化剂，用量占90％以上，是非常重要的有机合成中间体。
目前国内外工业生产咪唑的方法主要是采用α-二羰基化合物(乙二醛)、氨和醛为原料，经过缩合反应形成咪唑环，反应通常在间接釜式反应器进行。在间歇釜式反应器内采用滴加的方式进行：在持续搅拌下，将乙二醛和甲醛混合溶液在数小时或更长时间内缓慢滴加到氨源溶液中，滴加完成后继续保温数十小时使反应完全；传统间歇工艺存在生产成本高，副产物多以及安全性低的缺点。反应过程间歇式操作使得整个工艺过程效率偏低，釜内反应体系停留时间以及温度分布范围宽，收率普遍较低，钱永等(化工中间体，2012,09(4):49-52)提到咪唑的合成收率一般不超过50～60％。
反应如下式：
专利CN109422693A公开了一种利用微反应技术连续制备咪唑的方法，利用微通道反应连续流制备咪唑，但是其易堵住微通道管，因为咪唑反应会产生一些固体不溶物颗粒；其次专利的反应温度超过100℃产生大量的副产物，不利于后面咪唑浓缩精馏分离；再次专利反应为压力反应不利于安全生产。
迄今为止，尚未见以连续釜式反应器进行咪唑合成的报道。本发明提供一种采用连续釜式反应器连续合成咪唑的方法。
发明内容
针对现有间歇咪唑制备工艺存在的问题，本发明提出了一种简易高效的连续釜式反应器，并提供了收率较高、副产物少、设备操作简单、安全性高的连续化咪唑制备方法。
本发明的上述目的通过如下技术方案实现：
采用连续釜式反应器制备咪唑的方法，其特征在于，步骤如下：
S1、混醛和氨水物料的配制：将甲醛溶液和乙二醛溶液按照比例进行混合作为第一进料液，将氨源溶液作为第二进料液，待用；
S2、进料：开启连续釜式反应器搅拌，控制第一进料液流速为1mL/min～100mL/min和控制第二进料液流速为1mL/min～300mL/min同时进入反应器，使其充分反应，控制物料在反应器中的停留时间为5-10h；
S3、步骤S2得到的反应液通过连续釜式反应器溢流口流入浓缩釜中，收集反应液浓缩精馏得咪唑产品。
进一步的，所述第二进料液还包括催化剂，所述催化剂为氯化铵、醋酸铵、碳酸铵、碳酸氢铵、硫酸铵、磷酸铵或硝酸铵中的一种或几种。加入催化剂可明显提高反应速率。
进一步的，所述氨源优选氨水，还可以是醋酸铵、碳酸氢铵、碳酸铵、氯化铵或硫酸铵。
进一步的，所述步骤S1中甲醛溶液和乙二醛溶液的质量分数均为10％～50％，优选甲醛浓度为37％，优选乙二醛浓度为40％，甲醛与乙二醛的摩尔配比为1:1～1:2，氨水溶液的质量分数为10％～25％，催化剂与氨水的摩尔配比为0:10～1:40。
进一步的，所述步骤S2中反应温度控制在40～90℃。
进一步的，所述步骤S2中搅拌速度为50-300r/min。
进一步的，所述连续釜式反应器外连接有强制泵循环装置，通过外加强制泵循环装置增强反应介质的传质和传热，更好的促进反应的进行。这样连续釜式反应器在反应效率上得到空前提升。传统釜式间歇反应在没有深入研究咪唑反应动力学下导致反应时间过长(约30-35小时)，因此通过优化反应发现反应的停留时间仅仅为5-10小时，效率提升数倍。
反应中所用到的连续釜式反应器采用现有技术中常用的反应器，主要包括包括反应套筒、换热夹层、定速搅拌装置、外部换热管、冷热一体装置，反应套筒设置两个进料入口、两个换热口以及一个溢料出口，换热夹层与冷热一体装置相连。
本发明提供了连续法制备咪唑的新工艺，与现有间歇反应技术相比较，具有如下显著优势：
1)本发明采用连续釜式反应器制备咪唑，可以通过精准的控制流速及停留时间，有效减少反应过程中放热现象，提高安全性能，提高反应效率。
2)本发明在该连续釜式反应器内制备咪唑的反应技术，使得咪唑制备实现连续化生产，不仅减少甚至避免了副产物乌洛托品的含量，而且产品质量稳定，收率和生产效率(收率提高7-10个百分点，纯度>99％)得到提高，从而为技术的工业化奠定了基础。
为了使本发明所要解决的技术问题及有益效果更佳清楚明白，以下结合具体实施例，对本发明作进一步详细说明。另外，本发明的实施例，可以理解是示例性的，不能理解为对本发明的限制，本领域的技术人员在本发明的范围内可以对下述实施例进行变化、修改、替换和变型。
实施例1 采用连续釜式反应器制备咪唑的方法
S1混醛和氨水物料的配制：将质量分数35％的甲醛溶液和质量分数39％的乙二醛溶液按照摩尔比n(甲醛)：n(乙二醛)＝1:1.0进行混合，配制质量分数为17％的氨水溶液，不加催化剂，待用。
S2进料：通过蠕动泵将第一进料液混醛溶液按照进料流速11ml/min进行设定，将第二进料液氨水催化剂溶液按照进料流速15ml/min进行设定，设定反应温度为55℃，搅拌速度为100r/min，控制物料停留时间8.5h使其充分反应。
S3反应后处理：步骤S2的反应液通过溢流口流入浓缩釜中，收集反应液浓缩精馏得咪唑产品，经气相色谱检测分析，计算咪唑收率80％，纯度＞99％。
实施例2 采用连续釜式反应器制备咪唑的方法
S1混醛和氨水物料的配制：将质量分数37％的甲醛溶液和质量分数41％的乙二醛溶液按照摩尔比n(甲醛)：n(乙二醛)＝1:1.2进行混合，将质量分数为15％的氨水溶液和催化剂氯化铵按照摩尔比n(催化剂)：n(氨水)＝1:25进行混合，待用。
S2进料：通过蠕动泵将第一进料液混醛溶液按照进料流速8ml/min进行设定，将第二进料液氨水和催化剂溶液按照进料流速10ml/min进行设定，设定反应温度为65℃，搅拌速度为80r/min，控制物料停留时间6h使其充分反应。
S3反应后处理：反应液通过溢流口流入浓缩釜中，收集反应液浓缩精馏得咪唑产品，经气相色谱检测分析，计算咪唑收率88％，纯度＞99％。
实施例3 采用连续釜式反应器制备咪唑的方法
S1混醛和氨水物料的配制：将质量分数34％的甲醛溶液和质量分数35％的乙二醛溶液按照摩尔比n(甲醛)：n(乙二醛)＝1:1.4进行混合，将质量分数为18％的氨水溶液和催化剂醋酸铵按照摩尔比n(催化剂)：n(氨水)＝1:21进行混合，待用。
S2进料方式：通过蠕动泵将第一进料液混醛溶液按照进料流速9ml/min进行设定，将第二进料液氨水和催化剂溶液按照进料流速12ml/min进行设定，设定反应温度为85℃，搅拌速度为100r/min，控制物料停留时间5h，使其充分反应。
S3反应后处理：反应液通过溢流口流入浓缩釜中，收集反应液浓缩精馏得咪唑产品，经气相色谱检测分析，计算咪唑收率为81％，纯度＞99％。
实施例4 采用连续釜式反应器制备咪唑的方法
S1混醛和氨水物料的配制：将质量分数37％的甲醛溶液和质量分数41％的乙二醛溶液按照摩尔比n(甲醛)：n(乙二醛)＝1:1.3进行混合，将质量分数为19％的氨水溶液和催化剂氯化铵按照摩尔比n(催化剂)：n(氨水)＝1:23进行混合，待用。
S2进料：通过蠕动泵将第一进料液混醛溶液按照进料流速10ml/min进行设定，将第二进料液氨水和催化剂溶液按照进料流速15ml/min进行设定，设定反应温度为75℃，搅拌速度为80r/min，控制物料停留时间10h使其充分反应。
S3反应后处理：反应液通过溢流口流入浓缩釜中，收集反应液浓缩精馏得咪唑产品，经气相色谱检测分析，计算咪唑收率84％，纯度＞99％。
实施例5 采用连续釜式反应器制备咪唑的方法
S1混醛和氨水物料的配制：将质量分数32％的甲醛溶液和质量分数37％的乙二醛溶液按照摩尔比n(甲醛)：n(乙二醛)＝1:1.7进行混合，将质量分数为15％的氨水溶液和催化剂氯化铵按照摩尔比n(催化剂)：n(氨水)＝1:22进行混合，待用。
S2进料：通过蠕动泵将第一进料液混醛溶液按照进料流速15ml/min进行设定，将第二进料液氨水和催化剂溶液按照进料流速22ml/min进行设定，设定反应温度为70℃，搅拌速度为60r/min，控制物料停留时间9.5h使其充分反应。
S3反应后处理：反应液通过溢流口流入浓缩釜中，收集反应液浓缩精馏得咪唑产品，经气相色谱检测分析，计算咪唑收率85％，纯度＞99％。
对比例1 采用环合釜间歇制备咪唑的方法
1)混醛和氨水物料的配制：将质量分数35％的甲醛溶液103.6g和质量分数39％的乙二醛179.7g溶液按照摩尔比n(甲醛)：n(乙二醛)＝1:1.0进行混合，配制质量分数为17％的氨水溶液301.8g，不加催化剂，待用。
2)进料：将混醛溶液置于环合釜中，设定釜温为55℃，在此条件下滴加17％的氨水溶液，搅拌速度为100r/min，滴加完毕，控制物料反应时间8.5h使其充分反应。
3)反应后处理：待反应完毕，将反应液浓缩精馏得咪唑产品，经气相色谱检测分析，计算咪唑收率72％，纯度＞96％。
对比例2 采用环合釜间歇制备咪唑的方法
1)混醛和氨水物料的配制：将质量分数37％的甲醛溶液103.6g和质量分数41％的乙二醛216.8g溶液按照摩尔比n(甲醛)：n(乙二醛)＝1:1.2进行混合，将质量分数为15％的氨水溶液318.3g和摩尔比n：(氯化铵)：n(氨水)＝1:22的催化剂进行混合，待用。
2)进料：将混醛溶液置于环合釜中，设定釜温为65℃，在此条件下滴加15％的氨水和氯化铵混合液，搅拌速度为80r/min，滴加完毕，控制物料反应时间6h，使其充分反应。
3)反应后处理：待反应完毕，将反应液浓缩精馏得咪唑产品，经气相色谱检测分析，计算咪唑收率80％，纯度＞96％。
对比例3 采用环合釜间歇制备咪唑的方法
1)混醛和氨水物料的配制：将质量分数34％的甲醛溶液103.6g和质量分数35％的乙二醛272.3g溶液按照摩尔比n(甲醛)：n(乙二醛)＝1:1.4进行混合，将质量分数为18％的氨水溶液365.6g和摩尔比n：(氯化铵)：n(氨水)＝1:21的催化剂进行混合，待用。
2)进料：将混醛溶液置于环合釜中，设定釜温为85℃，在此条件下滴加18％的氨水和氯化铵混合液，搅拌速度为100r/min，滴加完毕，控制物料反应时间5h，使其充分反应。
3)反应后处理：待反应完毕，将反应液浓缩精馏得咪唑产品，经气相色谱检测分析，计算咪唑收率72％，纯度＞96％。
对比例4 采用环合釜间歇制备咪唑的方法
1)混醛和氨水物料的配制：将质量分数37％的甲醛溶液103.6g和质量分数48％的乙二醛234.9g溶液按照摩尔比n(甲醛)：n(乙二醛)＝1:1.3进行混合，将质量分数为19％的氨水溶液365.5g和摩尔比n：(氯化铵)：n(氨水)＝1:23的催化剂进行混合，待用。
2)进料：将混醛溶液置于环合釜中，设定釜温为75℃，在此条件下滴加19％的氨水和氯化铵混合液，搅拌速度为80r/min，滴加完毕，控制物料反应时间10h，使其充分反应。
3)反应后处理：待反应完毕，将反应液浓缩精馏得咪唑产品，经气相色谱检测分析，计算咪唑收率74％，纯度＞96％。
对比例5 采用环合釜间歇制备咪唑的方法
1)混醛和氨水物料的配制：将质量分数32％的甲醛溶液103.6g和质量分数35％的乙二醛294.4g溶液按照摩尔比n(甲醛)：n(乙二醛)＝1:1.7进行混合，将质量分数为19％的氨水溶液375.3g和摩尔比n：(氯化铵)：n(氨水)＝1:23的催化剂进行混合，待用。
2)进料：将混醛溶液置于环合釜中，设定釜温为75℃，在此条件下滴加19％的氨水和氯化铵混合液，搅拌速度为80r/min，滴加完毕，控制物料反应时间10h，使其充分反应。
3)反应后处理：待反应完毕，将反应液浓缩精馏得咪唑产品，经气相色谱检测分析，计算咪唑收率78％，纯度＞96％。
上述实施例、对比例产品收率及纯度等参数总结如下表：
-表示未加催化剂
发明中，采用连续釜制备咪唑方法与传统间歇式制备咪唑用了相平行的条件做了对比，发现用连续釜制备的咪唑产品收率都高于相同条件下间歇方式制备的咪唑，收率都相应地提高，实施例1与对比例1都没有加入催化剂，连续生产方式比间歇生产方式收率提高了8％；实施例2-5与对比例2-5虽然都加入了催化剂，但是收率同样提高了7-10个百分点，这对于工业生产中具有极其重要的意义。令发明人惊喜的是，不仅收率获得了大幅度提高，产品的质量也得到了提升，相对于传统方式的96％含量，通过连续釜制备的咪唑含量都超过了99％，发明人认为可能的原因是传统反应中，大量的物料参与反应，产生大量的热量，使得单位时间放热剧烈，为副反应提供了环境，降低了收率；而采用连续釜反应器，可以实现物料单位时间的有效混合和有效传热，减小甚至避免了副反应的发生，从而提高了收率及品质。
在本说明书的描述中，参考术语“一个实施例”、“一些实施例”、“示例”、“对比例”等的描述意指结合该实施例或对比例描述的具体特征、结构、材料或者特点包含于本发明的至少一个实施例或对比例中。在本说明书中，对上述术语的示意性表述不必须针对的是相同的实施例或对比例。而且，描述的具体特征、结构、材料或者特点可以在任一个或多个实施例或对比例中以合适的方式结合。
Claims (7)
- 一种采用连续釜式反应器制备咪唑的方法，其特征在于，步骤如下：S1、混醛和氨水物料的配制：将甲醛溶液和乙二醛溶液按照比例进行混合作为第一进料液，将氨源溶液作为第二进料液，待用；S2、进料：开启连续釜式反应器搅拌，控制第一进料液流速为1mL/min～100mL/min和控制第二进料液流速为1mL/min～300mL/min同时进入反应器，使其充分反应，控制物料停留时间为5-10h；S3、步骤S2得到的反应液通过连续釜式反应器溢流口流入浓缩釜中，收集反应液浓缩精馏得咪唑产品。
- 根据权利要求1所述的方法，其特征在于，所述第二进料液还包括催化剂，所述催化剂为氯化铵、醋酸铵、碳酸铵、碳酸氢铵、硫酸铵、磷酸铵或硝酸铵中的一种或几种。
- 根据权利要求2所述的方法，其特征在于，所述氨源为氨水。
- 根据权利要求3所述的方法，其特征在于，所述步骤S1中甲醛溶液和乙二醛溶液的质量分数均为10％～50％，甲醛与乙二醛的摩尔配比为1:1～1:2，氨水溶液的质量分数为10％～25％，催化剂与氨水的摩尔配比为0:10～1:40。
- 根据权利要求1所述的方法，其特征在于，所述步骤S2中反应温度控制在40～90℃。
- 根据权利要求1所述的方法，其特征在于，所述步骤S2中搅拌速度为50-300r/min。
- 根据权利要求1所述的方法，其特征在于，所述连续釜式反应器外连接有强制泵循环装置。
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