The uses and preparation methods of acetanilide_Kain Industrial Additives

Overview^[1-2]

Acetanilide is also known as N-phenylacetamide and acetaminophen, commonly known as antipyretic ice. Those crystallized from water are orthogonal white scaly shiny crystals or white crystalline powder. There is a burning smell. It is slightly soluble in benzene, xylene, toluene, acetone, ether and dioxane, but insoluble in petroleum ether. Chloroacetaldehyde hydrate can enhance the solubility of this product in water.

Purpose^[1]

Acetanilide can be used as a raw material for veterinary drugs (including fish) to prepare the intermediates chloroacetanilide and p-aminobenzene sulfonamide, and to further produce “sulfadimethoxypyrimidine” and “sulfa-methoxypyrimidine” “pyrimidine”, “sulfamethoxypyridazine”, “sulfathiazole”, “sulfamethylpyrimidine”, “sulfamethoxythiazole” and other drugs; used as raw materials for the pesticide herbicide “Huangcaoling”; dye vinyl sulfonyl It is a raw material for reactive dyes (reactive black 5, orange 16, yellow 13), fluorescent dyes, disperse dyes (disperse orange 10, 6), etc.; it is also used as a stabilizer for hydrogen peroxide; a raw material for organic synthesis; a raw material for sulfonamide drugs; Synthetic camphor raw material; cellulose ester coating additive.

Preparation method^[3]

1. Preparation of acetanilide by fractionation method

This method uses a fractionation device to prepare acetanilide. Add the reactants into the round-bottom flask one by one, then connect it to the fractionating column, insert a thermometer at the mouth of the column, and collect the steamed water and acetic acid in a conical flask. During heating, the thermometer reading is maintained at 110°C. When the reaction is completed, Pour the reactant into a beaker filled with cold water while it is hot, then cool it and let it stand for suction filtration to obtain the crude product which is recrystallized with water. Finally, use the weighing method to calculate the yield of the dried product. It was found through experiments that the yield of acetanilide prepared by fractional distillation is 20.7%, which is not high. Although the fractionation column in the device can remove the generated water from it, the fractionation column is not processed according to special experimental conditions, so it cannot absolutely follow the experimental intention. In addition, in the reaction system, due to the high reaction temperature, the general fractionation column It is difficult to fractionate the correct proportion of water and acetic acid within the specified time, which leads to an imbalance in the proportion of reactants, reducing the yield and even the experiment fails. In this reaction, aniline is easily oxidized, so the product is mostly light brown and yellow and becomes lumpy. It needs to be continuously recrystallized, which reduces the yield of acetanilide. Aniline is a toxic chemical. If the temperature is too high during the fractionation process, the excess mixed steam will not be liquefied and volatilized, which can cause harm to the environment and people. In addition, incomplete conversion of aniline is difficult to recover.

2. Preparation of acetanilide by reflux method

The reflux method uses a reflux device to synthesize acetanilide. Add the reactants into the round-bottomed flask one by one, install a straight condenser tube, heat to reflux over low heat. After the reaction is completed, pour the reactants into a beaker filled with water while stirring, cool and let stand for suction filtration, and repeat. For crystallization, the reactants can also be poured into ice water while hot, and cooled in it for a certain period of time to lower the temperature, thereby increasing the yield of acetanilide. This reaction uses aniline and excess glacial acetic acid to reflux to synthesize acetanilide, but it requires a long time to reflux, the yield is not high, and the product quality is not good. In the industrial preparation process, it needs to be heated for more than 6 to 8 hours. It can also be synthesized by refluxing an appropriate amount of aniline, acetic anhydride, glacial acetic acid and a small amount of zinc powder. In addition, aniline, glacial acetic acid and acetic anhydride can be refluxed together to prepare acetanilide. Both reflux methods use acetic anhydride as the acylating agent, which makes the reaction difficult to control and costly.

3. Radio frequency radiation synthesis method

The radio frequency radiation synthesis method uses parallel air capacitive coupling of radio frequency high-intensity electric fields to provide energy. When the reactants are placed in an electric field, the thermal effect can provide the activation energy required during the reaction, causing the molecules to be excited, thereby increasing the activity of the reactants. Radiofrequency radiation can heat the reactants inside and outside at the same time, and the temperature rises evenly without violent boiling. This heating accelerates the movement of molecules and increases the chances of collisions between molecules, which increases the reaction rate. In 1998, she used radiofrequency radiation to synthesize acetanilide. She used orthogonal design and uniform design respectively.Using the central design method, aniline and glacial acetic acid were used as raw materials to synthesize acetanilide, and possible influencing factors in the experiment were discussed. From the results, we can see that the yields obtained by these three methods are 53.9%, 47.1%, and 57.2% respectively. Although the yields of traditional synthesis methods cannot be obtained, radio frequency radiation has the advantages of non-pollution and safety in organic synthesis, so it It plays a special role in organic synthesis.

4. Synthesis of acetanilide by trace and semi-trace methods

In the traditional synthesis of acetanilide, the amount of reagents used is large and the reaction time is long. Since aniline is toxic, if the temperature is too high during fractionation, the excess mixed steam will not be liquefied and volatilized, which will cause harm to the environment and people. , In addition, the incompletely converted aniline after the experiment is difficult to recycle and will also cause harm to the environment and people. The micro- and semi-micro methods reduce the amount of reagents used in the experiment to micro and semi-micro amounts before conducting the reaction. This method reduces the amount of reaction reagents, shortens the reaction time, and reduces experimental expenses and environmental pollution.

5. Some other synthesis methods

First, react equal moles of hydrochloric acid with aniline to form chlorinated aniline, then add acetic anhydride, then add sodium acetate solution and stir. This method cannot react directly with acetic anhydride because the aniline cation generated when hydrochloric acid reacts with aniline lacks nucleophilicity. Sodium acetate must be added to increase the pH value of the solution, so that the cationic aniline ions become free aniline before the reaction can occur. This method consumes a large amount of sodium acetate, resulting in a waste of time and reagents and increasing industrialization costs. Aniline, acetyl chloride, and triethylamine are stirred together at room temperature to form acetanilide. This method is short in time and has a low reaction temperature, but acetyl chloride is expensive and prone to hydrolysis reactions with many by-products, making the reaction difficult to control and affecting the yield.