Originally published as The last step in organic synthesis! How to purify the reactants? Post-treatment of organic synthesis In organic synthesis, the problem of post-processing is often ignored by most people, who think that as long as the right synthesis method is found, the synthesis task can be twice the result with half the effort. This is true. The correct synthesis method is important, but the task of organic synthesis is to get a fairly pure product. Any reaction without 100% yield is always accompanied by more or less side reactions. More or less impurities are produced, and after the reaction is completed, the great problem is to separate the pure product from the reaction mixture. The purpose of reprocessing is to accomplish this task in the best possible way. Post-treatment has different solutions according to the purpose of the reaction. If in the laboratory, only to publish papers, the purpose of obtaining pure compounds is to make various spectra, then the problem is simple. The method of obtaining pure compounds is nothing more than column, TLC, preparative chromatography and other methods, without considering too many problems, and the compounds obtained are relatively pure; If it is for the purpose of industrial production, then the problem is complex, try to use simple, low-cost methods, the one in the laboratory will not work, if you still use the method in the laboratory, the enterprise will lose money. The following is a brief introduction to some of the methods in the industry: “ The inspection criteria for the post-treatment process are as follows: Expand the full text (1) Whether the product is recycled to the maximum extent and the quality is guaranteed; (2) Whether raw materials, intermediates, solvents and valuable by-products are recycled to the maximum extent; (3) Whether the post-treatment steps, both in terms of process and equipment, are sufficiently simplified; (4) Whether the amount of "three wastes" is minimized. " Several common and practical methods of post-processing: (1) separation and purification of organic acid and alkaline compounds: Organic compounds with acid-base groups can lose protons to form ionic compounds, which have different physical and chemical properties from the original parent compounds. The alkaline compound is treat with an organic or inorganic acid to obtain an amine salt, and that acidic compound is treated with an organic or inorganic base to obtain a sodium salt or an organic salt. According to the acidity and alkalinity of organic compounds, acids are generally formic acid, acetic acid, hydrochloric acid, sulfuric acid and phosphoric acid. The alkali is triethylamine, sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, etc. In general, ionic compounds have great solubility in water, but little solubility in organic solvents, and activated carbon can only adsorb non-ionic impurities and pigments. Acidic and alkaline organic compounds can be purified by using the above properties. The above properties are not universal for all acid-base compounds. In general, the larger the proportion of the molecular weight of acid-base groups in the molecule to the molecular weight of the whole molecule, the greater the water solubility of ionic compounds. The more water-soluble groups such as hydroxyl groups in the molecule, the greater the water solubility. Therefore, the above properties are applicable to acid-base compounds with small molecules. For macromolecular compounds,wiped film distillation, the water solubility is significantly reduced. Acid-base groups include amino groups. Acidic group include amido, carboxyl, phenolic hydroxyl, sulfonamido, thiophenol, 1, 3-dicarbonyl compounds, and that like. It is worth noting that amino compounds are generally basic groups, but when strong electron-withdrawing groups are attached, they become acidic compounds, such as amido and sulfonamido compounds, which are easy to lose protons and form sodium salts under the action of alkali such as sodium hydroxide and potassium hydroxide. Neutralization and adsorption method: it is a method to recover and purify acid-base products by converting acid-base compounds into ionic compounds, dissolving them in water, adsorbing impurities with activated carbon and filtering to remove impurities and mechanical impurities that do not contain acid-base groups, and then adding acid-base neutralization to return to the parent molecular state. Because activated carbon does not adsorb ions,cbd centrifugal extractor, the product loss caused by activated carbon adsorption is negligible.
Neutralization extraction method: It is a common method in industrial processes and laboratories. It uses the characteristics that acid-base organic compounds are dissolved in water when they generate ions and the parent molecules are dissolved in organic solvents. By adding acids and bases, the parent compounds generate ions and dissolve in water to achieve phase transfer, and non-water-soluble organic solvents are used to extract non-acid-base impurities. Dissolving in an organic solvent to separate the impurities from the product. Salification method: for water-insoluble macromolecular organic ionic compounds, organic acidic and alkaline compounds can be salted and crystallized in the organic solvent, while non-salifying impurities remain in the organic solvent, thus realizing the separation of organic acidic and alkaline compounds from non-acidic and alkaline impurities. Acidic and alkaline organic impurities can be separated by recrystallizing the precipitated crystals. The salt of the organic acid and base compound of the macromolecule can also be washed by water to remove the impurities of the acid and base compound of the micromolecule which has been salted and has water solubility. In the case of water-soluble organic ionic compounds, impurities can be separated from the product by forming a salt in water, removing the water by azeotropic distillation or direct distillation, and thoroughly washing the residue several times with an organic solvent. The above three methods are not isolated. According to the nature of the compound and the requirements of the product quality standards, a combination of methods can be used to obtain products of considerable purity as far as possible. (2) Several special organic extraction solvents: N-butanol: Most small alcohols are water-soluble, such as methanol, ethanol, isopropanol, n-propanol, etc. Most high molecular weight alcohols are insoluble in water, but are lipophilic and soluble in organic solvents. However, the intermediate alcohol solvent, such as n-butanol, is a good solvent for machine extraction. N-butanol itself is insoluble in water, and it has the common characteristics of small molecular alcohol and large molecular alcohol. It can dissolve some polar compounds that can be dissolved by small molecular alcohols, while it is insoluble in water. Using this property, n-butanol can be used to extract polar reaction products from aqueous solutions. Butanone: Properties intermediate between small and large ketones. Unlike acetone, which is soluble in water, butanone is insoluble in water and can be used to extract the product from water. Butyl acetate: The property is between small molecule and macromolecule ester. Its solubility in water is very small, unlike ethyl acetate, which has a certain solubility in water. It can extract organic compounds from water, especially amino acid compounds. Therefore, it is commonly used in the antibiotic industry to extract cephalosporin, penicillin and other macromolecular compounds containing amino acids. Isopropyl ether and tert-butyl ether: The properties are between small molecular ether and large molecular ether, decarboxylation after extraction ,wiped film evaporator, the polarity of both is relatively small, similar to n-hexane and petroleum ether, and the solubility of both in water is small. Can be used as a crystallization solvent and an extraction solvent for molecules with very small polarity. It can also be used as a solvent for the crystallization and extraction of more polar compounds. (3) After the reaction Extraction should be used first to remove some impurities, which is based on the different solubility of impurities and products in different solvents. (4) washing off a part of alkaline impurities with aqueous solution of dilute acid For example, if the reactant is basic and the product is neutral, the basic reactant can be washed away with dilute acid. Uch as the acylation of amino compounds. (5) washing off a part of acidic impurities with dilute alkali aqueous solution If the reactant is acidic and the product is neutral, dilute alkali can be used to wash away the acidic reactant. Uch as esterification of carboxylic compounds. (6) washing off a part of water-soluble impurities with water For example, in the esterification reaction of a lower alcohol, the water-soluble reactant alcohol can be removed by washing with water. (7) If the product is to be crystallized from water And the solubility in the aqueous solution is large, so the method of adding inorganic salts such as sodium chloride, ammonium chloride and the like to reduce the solubility of the product in the aqueous solution, namely salting-out, can be tried. (8) Two immiscible organic solvents may sometimes be used as extractants. For example, when the reaction is carried out in chloroform, petroleum ether or n-hexane can be used as an extractant to remove a part of the impurities with small polarity, and conversely, chloroform extraction can be used to remove the impurities with large polarity. (9) Two mutually soluble solvents are sometimes variably incompatible with one another by addition of another substance. For example, in the case where water is used as a solvent, after the reaction is completed, inorganic salts such as sodium chloride and potassium chloride may be added to the system to saturate the water, and then acetone, ethanol, acetonitrile, and other solvents may be added to extract the product from the water.
(10) Method of crystallization and recrystallization: The basic principle is to use the similarity compatibility principle. Namely, the compound with strong polarity is recrystallized by using a polar solvent, and the compound with weak polarity is recrystallized by using a non-polar solvent. For compounds that are difficult to crystallize, such as oils and gels, the method of mixing solvents is sometimes used, but the combination of mixed solvents is very learned, and sometimes it can only be based on experience. Generally, polar solvent and non-polar solvent are collocated, and the collocation principle is to select the proportion of polar solvent and non-polar solvent according to the polarity of products and impurities. If the polarity of the product is large and the polarity of the impurity is small, the proportion of polar solvent in the solvent is greater than that of non-polar solvent; if the polarity of product is small and the polarity in the impurity is large, the proportion of non-polar solvent in the solvent is greater than that of polar solvent. Commonly used combinations are: alcohol-petroleum ether, acetone-petroleum ether, alcohol-n-hexane, acetone-n-hexane, etc. However, if the product is very impure or the nature of the impurity is extremely similar to that of the product, the cost of obtaining a pure compound is multiple recrystallizations, and sometimes multiple refinements. At this time, the impurities that are generally difficult to remove must be similar to the nature and polarity of the product. The removal of impurities can only be considered from the reaction. (11) Methods of steam distillation, vacuum distillation and rectification: This is a common method for purifying low melting point compounds. In general, the recovery rate of vacuum distillation is relatively low, because the concentration of the product is gradually reduced with the continuous evaporation of the product. In order to ensure that the saturated vapor pressure of the product is equal to the external pressure, the temperature must be continuously increased to increase the saturated vapor pressure. Obviously, the temperature can not be increased indefinitely, that is, the saturated vapor pressures of the products can not be zero, that is, the products can not be completely evaporated. A certain amount of product remains in the distillation equipment and is dissolved by the less volatile components in the equipment, as evidenced by a large amount of residue. Steam distillation provides near quantitative recovery of volatile low melting organic compounds. This is because during steam distillation, the sum of the saturated vapor pressure of all components in the kettle plus water is equal to the external pressure. Due to the existence of a large amount of water, the saturated vapor pressure has reached the external pressure at 100 ℃. Therefore, when the temperature is below 100 ℃, the product can be completely distilled out with the steam, and the recovery rate is close to complete. Steam distillation is particularly suitable for systems containing tar. Because the tar has two negative effects on the product recovery: one is that the tar can dissolve a part of the product so that it can not be distilled out due to the influence of the equilibrium relationship; the other is that the high boiling point of the tar makes the temperature too high during distillation so that the product continues to decompose. The steam distillation can recover the product from the tar nearly quantitatively, and avoids the overheating polymerization of the product in the distillation process, and the yield is increased by about 3-4% compared with the vacuum distillation. Although steam distillation can improve the recovery rate of volatile components, it is difficult to solve the problem of product purification, because volatile impurities are distilled out together with the product. At this time, the method of distillation can not only ensure the recovery rate of the product, but also ensure the quality of the product. It should be noted that steam distillation is only a special case of azeotropic distillation and other solvents may be used. Azeotropic distillation is not only suitable for product separation, but also suitable for dehydration of reaction system, solvent and product. Compared with the dehydration process of molecular sieve and inorganic salt, it has the advantages of simple equipment, easy operation and no consumption of other raw materials. For example, in the production of ammoximic acid, there are several polar groups such as amino and carboxyl in the molecule, which can form hydrogen bonds with water, alcohol and other molecules, so that there is a large amount of free and hydrogen-bonded water in the ammoximic acid. If the general vacuum drying method is used, it is not only time-consuming, but also easy to cause the decomposition of the product. At this time, azeotropic distillation can be used to remove the water molecules. The specific operation is to stir the ammoximic acid and methanol under reflux for several hours to remove water molecules and obtain anhydrous aminothiazolyloximic acid. For another example, when free or hydrogen-bonded methanol is present in the molecule, the methanol can be removed by refluxing with another solvent, such as n-hexane, petroleum ether, or the like. It can be seen that azeotropic distillation plays an important role in the separation process of organic synthesis. (12) Supramolecular method: The recognition of the molecule is used to purify the product.
(13) Method of decolorization: Activated carbon, silica gel, alumina, etc. Are generally used. Activated carbon adsorbs non-polar compounds and small molecular compounds, while silica gel and alumina adsorb polar and macromolecular compounds, such as tar. For the system with both polar and nonpolar impurities, the two should be combined at the same time. The system that is difficult to decolorize can be removed by silica gel and alumina. It is sometimes difficult to decolorize acidic and alkaline compounds. When acidic compounds are neutralized with alkali to form ionic compounds and dissolved in water for decolorization, in addition to decolorizing once to remove alkaline impurities under weak alkaline conditions, the system should be gradually neutralized to weak acidity, and then decolorized once to remove acidic impurities, so that the pigment can be completely removed. Similarly,wiped film distillation, when the alkaline compound is neutralized with acid until it is weakly alkaline and dissolved in water for decolorization, in addition to decolorizing once to remove acidic impurities under weakly acidic conditions, the system should be gradually neutralized to weakly alkaline and then decolorized once again to remove alkaline impurities. (Source: Internet) (Photo: Pixabay) Back to Sohu to see more Responsible Editor:. toptiontech.com
