4-Dimethylaminopyridine [Overview]
4-Dimethylamino-pyridine (English name 4-dimethylamino-pyridine, referred to as DMAP) is an efficient catalyst with fast reaction speed, mild reaction conditions, high reaction yield, wide range of solvent selection, and low catalyst dosage. and many other advantages. It is widely used in fine chemicals, chemical pharmaceuticals, biochemicals, pesticides and other industries.
4-Dimethylaminopyridine [Physical and Chemical Properties]
DMAP is a colorless crystal with a melting point of 112~113°C (recrystallized from ethyl acetate or diisopropyl ether). It is easily soluble in methanol, ethyl acetate, chloroform, dichloromethane, and 1,2-dichloroethane. , acetone, acetic acid, slightly soluble in cold hexane, cyclohexane and water. DMAP solution or emulsion applied to rabbit skin will cause necrosis and severe burns to the mucous membrane of the rabbit eye. Care should be taken to avoid contact with the skin. If it is accidentally touched, it can be washed with dilute acid.
4-Dimethylaminopyridine [Preparation method]
1. Bipyridinium salt method This method uses pyridine and thionyl chloride as raw materials to first prepare the intermediate 4-(4-pyridyl)pyridinium chloride hydrochloride, and then mix it with dimethylamine (hereinafter referred to as DMA) Or dimethylformamide (hereinafter referred to as DMF) reaction to prepare DMAP. At present, this method is commonly used in domestic production, but it always has the disadvantages of low yield, inconvenient operation, high pollution, and large amounts of three wastes. The reaction formula is as follows:
Figure 1 is the reaction equation of the bispyridinium salt method
2. R-pyridone method: DMAP is prepared by using r-pyridone as raw material and reacting with hexamethylphosphoric triamide (HMPT) at 220°C for 3 to 4 hours. The preparation of r-pyridone, the main raw material of this method, requires diethyl oxalate and acetone to undergo condensation, hydrolysis, ammoniation, decarboxylation and other steps. The process flow is complex and the overall yield is low. The reaction formula is as follows:
Figure 2 is the reaction equation of r-pyridone method
3.4-Chloropyridine method uses 4-chloropyridine as raw material and reacts with DMA to prepare DMAP. The process flow is short and easy to operate, but the main raw material 4-chloropyridine is expensive and difficult to source. The reaction formula is as follows:
Figure 3 shows the reaction equation of the 4-chloropyridine method
4.4-pyridine sulfonic acid method uses 4-pyridine sulfonic acid as raw material and reacts with dimethylamine in the presence of zinc chloride to prepare DMAP. This method also has the disadvantages of difficult source of raw materials, high price and low yield. The reaction formula is as follows:
Figure 4 is the reaction equation of the 4-pyridinesulfonic acid method
5.4-Phenoxypyridine method: DMAP is prepared by reacting 4-phenoxypyridine with dimethylamine at 200~210℃ in the presence of HBr. This method has difficult sources of raw materials, harsh reaction conditions, and is difficult to industrialize. The reaction formula is as follows:
Figure 5 is the reaction equation of the 4-phenoxypyridine method
6.4-Trimethylsiloxypyridine method uses 4-trimethylsiloxypyridine as raw material, HgCl2 as catalyst, and reacts with dimethylamine to obtain DMAP. The main disadvantages of this method are the difficulty in sourcing raw materials, large catalyst pollution, and difficulty in treatment. The reaction formula is as follows:
Figure 6 is the reaction equation of the 4-trimethylsiloxypyridine method
7.4-Aminopyridine method uses 4-aminopyridine as raw material and reacts with dimethyl sulfate to obtain DMAP. This method is simple to operate, but the synthesis yield is very low, and 4-aminopyridine is expensive, so it is not suitable for industrial production. The reaction formula is as follows:
Figure 7 is the reaction equation of the 4-aminopyridine method
8. The 4-cyanopyridine method uses 4-cyanopyridine as the main raw material. It is first quaternized with 2-vinylpyridine, then reacted with dimethylamine, and finally treated with alkali to obtain high yield and high purity DMAP. The unreacted raw material 2-vinylpyridine is circulated in the device.
4-Dimethylaminopyridine【Application】
DMAP, as a catalyst, can be used in the following types of reactions:
Di-tert-butylpyridine
1. Acylation reaction DMAP can not only catalyze the acylation reaction of simple reactants, but also significantly improve the reaction rate and yield of the acylation reaction of some alcohols and phenols with high steric hindrance and low activity. DMAP can be used as a catalyst. The yield of many acylation reactions can reach more than 90%, and the reaction conditions are mild and can be realized at room temperature.
2. Esterification reaction The esterification reaction of carboxylic acid and alcohol needs to be carried out at a higher temperature. Under the action of DMAP catalyst, it can be carried out quickly at room temperature. For example, the esterification reaction of amino acids needs to be carried out at high temperatures, but racemization products are easily obtained at high temperatures. When DMAP is added, not only is esterification rapid at low temperature, but also the racemization of raw materials and products during the reaction process is avoided, greatly improving the reaction yield.
3. Etherification reaction of alcohol and phenol DMAP can also be used to catalyze the etherification reaction of alcohol and phenol. For example, DMAP is used as a catalyst to catalyze the reaction between alcohol and trityl group., and at the same time, it can shorten the reaction time, reduce by-products, and reduce production costs. Using DMAP or a composite catalyst system containing DMAP can significantly improve the product purity and production efficiency of the phosphorylation process. DMAP not only has a significant catalytic effect on phosphorylation, but also has significant catalytic activity on the synthesis of pyrethroids from chrysanthrin chloride.
4-Dimethylaminopyridine [Main Reference Materials]
[1]Guo Yufeng, Li Jingyin, Li Shufang, Li Min. Catalysis of 4-dimethylaminopyridine[J]. Chemical Reagents, 2001(06):338-339+352.
[2]Liu Shanhe. Synthesis of 4-dimethylaminopyridine[J]. Fine Chemicals, 2014, 31(09):1165-1168.
[3] Sun Jiguo, Zhou Zicheng, Xia Lingyuan. Application of 4-dimethylaminopyridine (DMAP) in pharmaceutical synthesis [J]. Journal of Cangzhou Normal University, 2014, 30(01): 49-53.
[4] Duan Xiangsheng, Zeng Wenping, Nie Ping. Synthesis and application of 4-dimethylaminopyridine [J]. Fine Chemical Intermediates, 2001(05):5-8.
[5]Cao Zhiyong, Wu Guanghua. Application of 4-dimethylaminopyridine (DMAP) in pharmaceutical synthesis [J]. Fine Chemical Raw Materials and Intermediates, 2010(03):10-12.
[6] Fan Xiaozhen, Liu Fang. Application of 4-dimethylaminopyridine in the synthesis of fine chemicals [J]. Journal of Cangzhou Normal University, 2017, 33(02):18-23.
[7] Fan Xiaozhen, Xu Xi. Application of 4-dimethylaminopyridine in pesticide synthesis[J]. Journal of Cangzhou Normal University, 2015, 31(01):42-46.
