Mixing equipment for pharmaceuticals and pesticides

In industries such as fine chemicals, pharmaceuticals, and pesticides, there are various types of unit operations involved, each with its own characteristics. Conventional physical processes such as distillation, cooling, dissolution, concentration, and some kinetically controlled homogeneous reactions are not controlled by stirring. General stirring equipment (such as standard enamel kettles) can meet process requirements, and the focus of design is more on energy consumption and purchase costs.

However, the stirring equipment for most unit operation processes still requires professional design, including continuous nitrification, chlorination, addition, condensation, substitution, fluorination, acylation, sulfonation, ammonolysis, oxidation, extraction, crystallization, hydrolysis, water washing, etc. How to grasp the core issues of each process for targeted stirrer design depends on long-term engineering experience and rich professional knowledge. The original view of these agitators is not only an equipment issue, but more of a process issue. Only by being familiar with the process, grasping the essence of the problem, and matching the chemical characteristics of the reaction with the transfer characteristics of the reactor, can the process effect be maximized.

◇Continuous nitrification reaction

Taking the multi reactor series continuous mixed acid nitration process of benzene, chlorobenzene, and toluene as an example, the number of reactors in series, single reactor volume, aspect ratio, built-in heat exchange tubes, type of agitator, circulation rate, shear rate, flow pattern, and other parameters are designed based on reaction kinetics in order to achieve ideal residence time distribution and conversion rate. In addition, the design of the agitator also needs to consider: 1. The heat transfer capacity corresponding to the conversion rate, which depends on the heat transfer coefficient at the same heat transfer area and reaction temperature, and the height of the heat transfer coefficient is closely related to the design of the agitator; 2. The size of the shear amount is too large, which leads to high energy consumption and difficulties in the subsequent oil-water separation process. The shear amount is too small, which directly affects the dispersion degree of the water oil phase and reduces the reaction rate.

◇chlorination

The chlorination of organic compounds (such as aromatic hydrocarbons and heterocyclic compounds) is mostly carried out using a single pot intermittent operation method. Due to the existence of multi-stage chlorination reactions and the small difference in activation energy between each reaction, it is difficult to coordinate the conversion rate of raw materials, the selectivity of target products, the utilization rate of chlorine qi, and reaction time.

Optimizing the mixer and increasing the aspect ratio of the reactor are effective methods to improve the dispersion of chlorine gas and accelerate the reaction. Extending the residence time of chlorine gas can also improve its utilization rate to some extent. However, more than 10% of chlorine gas may still be wasted.

The stirred reactor designed by Yuanzheng Company with double kettle series intermittent operation can effectively solve these problems:

1. The first and last reactors can be carried out under different reaction conditions, providing the possibility of improving selectivity;

2. The first kettle does not pursue the utilization rate of chlorine, which can improve the chlorine flow rate, shorten the reaction time, and increase the conversion rate;

After the first reactor reaction is completed, the concentration of raw materials in the final reactor is still high, making it difficult for chlorine to overflow and increasing the utilization rate of chlorine to over 99%.

Of course, this process can also adopt a three pot continuous process to increase production capacity and simplify operation.

In short, whether it is a single pot intermittent, double pot intermittent, or three pot continuous process, the reasonable design of the agitator is crucial.

◇oxidation reaction

The reaction using pure oxygen oxidation should use a self-priming stirred reactor, as detailed in "Liquid phase catalytic hydrogenation and other gas-liquid reaction technologies and equipment". Unlike catalytic hydrogenation, oxygen purity is generally not as high as hydrogen, and self-priming oxidation reactors still need to be continuously vented with a small flow rate to avoid inert gas enrichment. Of course, there are also some large reactors with low raw material concentration, low oxygen consumption, and low reaction pressure that use a combination of turbine blades and multi-layer wide blade axial flow blades, such as the 80m3 reactor for oxygen oxidation of glyphosate to produce glyphosate.

Self suction stirred reactors are not suitable for air oxidation reactors because high concentrations of nitrogen in the air quickly accumulate in the gas phase space, and nitrogen is mainly circulated between the gas and liquid phases, causing the oxidation reaction to terminate quickly. Therefore, the air oxidation reactor should adopt a multi-layer stirred reactor with a large aspect ratio. As for the design of the mixer, it is closely related to factors such as system viscosity, ventilation rate, reaction pressure, difficulty in recovering solvents from exhaust gas, and oxygen concentration requirements in exhaust gas.

◇Quick response

For some reactions with fast reaction rates, in order to control the reaction rate, reaction temperature, and impurity content, one of the reaction materials is added dropwise (or flow) to make the reaction relatively mild. This method is very effective, but there are still drawbacks:

When the dropwise addition of components occupies a high volume percentage, the reactor material level changes greatly, and the flow situation at the liquid level dropwise addition position also changes greatly. The diffusion speed of the raw material concentration decreases with the increase of the liquid level;

When the circulation capacity of the mixer is insufficient, the concentration of the raw materials at the drip position is too high, the local reaction rate is too fast, and the reaction is prone to forming hot spots. Local overheating makes it difficult to control the side reactions.

3. Some reactions are fast, and in the later stage of dropwise addition, the viscosity of the system increases due to the precipitation of products. At this time, the components added dropwise are more difficult to diffuse, especially in pseudoplastic fluids.

The original design of these fast reaction stirrers has its own unique features, and the main idea is how to use reasonable design to quickly disperse the added components and eliminate the hot spots of the reaction. At the same time, it is necessary to optimize the drip location and drip method, and for some fast reactions, the initial concentration of the drip components needs to be diluted in advance.

◇crystallization

Crystallization is the process of solute precipitation from a solution, and there are two methods: evaporation concentration crystallization and cooling crystallization.

In the fields of fine chemicals, pharmaceuticals, pesticides, etc., crystallization is not only a means of separating solutes from solutions, but also an important method of purification, which greatly increases the difficulty of designing crystallization kettles.

So, the design of the stirring crystallization kettle should consider multiple factors:

1. Sufficient circulation capacity to maintain particle suspension, solute concentration uniformity, and temperature uniformity;

2. Low shear capacity, reducing damage to crystal form;

3. Improve the smoothness of the inner wall and components of the kettle, and reduce the sticking of the kettle material;

When it is impossible to avoid sticking to the kettle, scraping and stirring can be considered;

5. Reduce the temperature difference in heat transfer, keep the solution at a lower supersaturation, increase the ratio of crystal growth rate to nucleation rate, and obtain larger and more complete crystals with higher product purity.

◇Liquid-liquid dispersion

Liquid liquid dispersion exists in many process engineering, such as hydrolysis, extraction, water washing, etc. The purpose of stirring is to evenly disperse the dispersed phase in the continuous phase as small droplets as possible, increasing the mass transfer area and shortening the operating time.

High shear turbine blades are commonly used in liquid-liquid dispersion agitators, and mature methods have been developed to calculate the critical speed at which the two-phase interface disappears, the interfacial area between the two phases, and the size of dispersed droplets. The density difference, viscosity difference, and interfacial tension between the two phases are the three important parameters of ZUI.

The liquid-liquid dispersion agitator designed according to the above method operates at a speed much higher than the critical speed, and its energy consumption is often relatively high, especially for equipment with a large aspect ratio and volume. The setting of multi-layer shear blades further increases energy consumption.

The original design of the liquid-liquid dispersion mixer pays great attention to energy consumption while ensuring process efficiency. Using a layer of high-speed turbine blades with a smaller diameter and placing them near the interface is a method that is both energy-saving and ensures process efficiency. When the length to diameter ratio of the equipment is large, a layer of axial flow blades can be installed in the continuous phase to compensate for the defect that the turbine blades cannot affect the entire liquid phase, and the energy consumption of axial flow blades is only 10% to 20% of that of turbine blades.

◇Solid-liquid suspension

There are two situations in solid-liquid suspension that require special design: one is slurry suspension with high solid content, and general axial flow impellers will fail. The original SP306 arc blade propeller was specifically developed for this process and is suitable for systems with solid content up to 35%~65%, especially when the suspension has a certain viscosity due to small solid particles. It can also be used in the presence of a small amount of gas. The suspension of another type of metal powder, such as iron powder reduction process, reduction process using skeleton nickel as catalyst, dehydrogenation process using copper as catalyst, production process of organic tin, etc., is difficult due to the huge density difference between metal and liquid phase, and the agitator is also prone to wear or corrosion. Most types of agitators in the original SP series can adapt to this situation as long as they are designed reasonably. If necessary, surface hardening, lining and other measures can be taken on the blades to prevent wear and corrosion.