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Differences in the crystal forms of compounds directly affect their stability, the rate of absorption, hygroscopicity, purity, and so on. Do anyone have any insights on this topic? The general principles for selecting crystallization solvents and the methods for determining crystalline purity. General principle for selecting a crystallization solvent: the component to be separated should have high solubility at high temperatures and low solubility at low temperatures ; Impurities are either insoluble in both hot and cold conditions or readily soluble in both. The boiling point should be appropriate, neither too high nor too low; for example, ether is not suitable for use. Alternatively, a method for determining crystalline purity can be employed by taking advantage of the differences in solubility of substances and impurities in different solvents: uniform physicochemical properties ; Melting distance of solid compounds ≤ 2℃ ; A single spot is observed on TLC or PC development ; HPLC or GC analysis shows a single peak. Modern crystallography mainly includes the following branches: (1) Crystallogeny: the study of the processes and mechanisms underlying the formation, growth, and transformation of natural and artificial crystals, as well as the factors that control and influence them. (2) Geometrical crystallography: Studies the shapes of the geometric polyhedra on the surface of crystals and the patterns among them. (3) Crystallology: The study of the regularity in the arrangement of particles within a crystal’s internal structure, as well as the imperfections in crystal structures. (4) Crystallochemistry: The study of the regularities governing the chemical composition and crystal structure of crystals, as well as the relationships between these aspects and the physical and chemical properties of crystals. (5) Crystallophysics: The study of the various physical properties of crystals and the mechanisms behind their formation. Regarding solvents: they are key to the preparation of crystals. In addition to what Yang Dongyu mentioned, when making a choice, it is possible to test the solubility using small amounts of various solvents, both when the material is cold and when it is hot. Ethanol is generally the preferred choice. Additionally, it is advisable to choose a single solvent whenever possible; this also helps to address the issue of recycling mother liquor on a large scale, thereby reducing costs. In research, mixed solvents generally yield better results. Safety is also a factor, as is low cost. Crystallization conditions: mainly refer to temperature, pressure, and whether stirring is used, etc. Temperature is very important; generally we use low-temperature refrigeration, but sometimes high temperature is also needed for preservation! This mainly requires understanding the relationship of its solubility to determine the crystallization temperature. Stirring is also a factor that affects both the crystal form and the rate of crystallization. Determination of crystalline purity: All are standard conventional methods. However, for certain products, experience can be used as a guide when producing them in large quantities. For example, after multiple recrystallizations of a sample, if the desired crystal form appears, and based on previous test results, the purity should be quite high – one can verify this by using HPLC. Additionally, the conditions for gradual temperature reduction have a significant impact on the crystal form and yield. Another factor is the timing of adding seed crystals: if they are added too early, the crystals that form are usually finer in size ; If it is added late, crystal nuclei may already have formed in the solution, resulting in crystals that could contain impurities. The recrystallization method takes advantage of the different solubilities of the various components in a solid mixture in a certain solvent to separate them from one another. The simple procedure for recrystallization involves first dissolving the impure solid in an appropriate hot solvent to obtain a nearly saturated solution. The insoluble impurities are removed by filtration while the solution is still hot. The filtrate is then cooled to allow crystals to precipitate from the supersaturated solution, with the soluble impurities remaining in the mother liquor. The crystals are separated from the mother liquor through vacuum filtration, dried, and their melting point is determined. If the purity still does not meet the requirements, recrystallization can be repeated until the desired purity is achieved. Regarding the selection of solvent, choosing an appropriate solvent is of great importance for the success of recrystallization. A good solvent must meet the following conditions: 1. It should not react chemically with the substance to be purified; 2. It should be able to dissolve a large amount of the substance to be purified at higher temperatures, but only a small amount at room temperature or lower temperatures ; 3. The solubility of the impurities is either very high or very low; in the former case, the impurities remain in the mother liquor, while in the latter case, they are removed during filtration while the mixture is still hot ; 4. The boiling point of the solvent should not be too low, nor too high. When the boiling point of the solvent is too low, the temperature difference between the solution preparation and cooling crystallization steps is small, resulting in little change in the solubility of the compound and thus affecting the yield. Moreover, working with solvents of low boiling points is also inconvenient. The boiling point of the solvent is too high, making it difficult to remove the solvent adhering to the crystal surface. 5. It can produce good crystals. When several solvents are suitable, the best one should be selected based on factors such as the recovery rate of crystallization, the ease of operation, the toxicity and flammability of the solvent, and its cost. Regarding the precipitation of crystals: After the filtrate obtained through filtration is cooled, crystals will precipitate. By rapidly cooling the solution with cold water or ice water and stirring it vigorously, crystals with very small particles can be obtained; if the hot solution is allowed to cool slowly at room temperature, uniform and larger crystals can be formed. If crystals do not precipitate even after the solution has cooled, the container wall below the liquid level can be rubbed with glass, more solute can be added, or the temperature of the solution can be lowered further (by using ice water or other freezing solutions). If no crystals form and an oily substance remains after the solution is cooled, it can be reheated until a clear hot solution is obtained; thereafter, it is allowed to cool naturally while stirring the solution continuously with a glass rod, rubbing against the container walls, or adding seeds to accelerate the formation of crystals. If oil-like substances continue to emerge, stir vigorously immediately to disperse the oil droplets. The crystallization process is indeed a field of study; in China, the leading expert in this area is Academician Wang Jingkang from the School of Chemical Engineering at Tianjin University. There are many theoretical books on this subject, but when it comes to each specific type of substance or individual substance, they are not entirely the same. The common aspects may be theoretical, while discussions on the crystallization processes specific to each type of compound might be most helpful to everyone. The selection of solvent (single or mixed), crystallization temperature, stirring speed, stirring method, choice of supersaturation level, crystal growth time, as well as the method and rate of adding the solvent, etc. Additionally, during the processes of dissolution, crystallization, and crystal growth, the aforementioned parameters such as temperature, stirring speed, time, and addition method and rate vary as well. So with all these factors coming together, it seems even more difficult. Generally speaking, the main conditions should be selected first to enable the crystallization process to proceed and yield crystals, after which those conditions can be optimized. Pilot testing and production can only proceed once the conditions are met. If it is theoretical research, the focus might be different. In the case of applied research, it is relatively easy to choose a solvent; the key issue is whether this solvent can be used to reach a supersaturated state, and whether it is feasible to control the range of supersaturation. If the supersaturation point is difficult to determine, or if the degree of supersaturation is not sufficient, it is hard to induce crystallization, let alone promote crystal growth. At this point, it may be necessary to consider composite solvents in order to adjust the supersaturation range. So I think the most important part of the crystallization process is the crystal precipitation process, and it is at this stage that controlling various conditions is of utmost importance. Control the crystallization process well; about 60% of the crystallization is completed. The crystal growth process is relatively easier to control; it mainly involves adhering to the optimized parameters and maintaining the right conditions, so there are generally no major issues. Problems also rarely arise during the scaling up process. If conducting fundamental research where the physical properties are not yet well understood, studying the crystallization process may require a significant amount of time and effort. But once the whole process is understood, it is still very valuable.