Overview of the preparation of (S)-4-hydroxyethylpyridine
Pyridine pesticides, as the world’s fourth-generation new pesticides, have obvious advantages. Pesticides containing pyridine rings are not only highly efficient, low-toxic, and long-lasting, but also have good environmental compatibility with humans and organisms. They are in line with the development requirements and trends of pesticides, and pyridine and its derivatives are important intermediates for synthesizing pesticides and medicines. body. New compounds obtained by replacing benzene rings with pyridine often have higher biological activity or lower toxicity. In recent years, people have used various heterocycles, especially pyridine groups, to replace benzene rings or benzene rings in existing molecular structures. It is to introduce other groups into known molecules containing pyridine groups for derivatization, in order to obtain compounds with new activities. As a widely used fine chemical product, (S)-4-hydroxyethylpyridine can synthesize vinylpyridine and many other fine organic chemical intermediates. It has a wide range of applications in polymer materials, surfactants, medicines, pesticides, etc. purpose and has high development value.
Preparation of (S)-4-hydroxyethylpyridine
At present, it can be divided into two different technical routes according to different synthesis processes: one is to react under high temperature and high pressure, and 4-methylpyridine and formaldehyde are liquid-phase catalyzed to obtain (S)-4-hydroxyethylpyridine; The second is to improve the process so that methylpyridine and formaldehyde react under normal pressure. Based on domestic and foreign patent information and existing research literature on ethanolic pyridine series products, the synthesis of (S)-4-hydroxyethylpyridine mainly uses carboxylic acids as catalysts. The reaction under high pressure is prone to side reactions and the product is not easy to preserve. Features.
Specific steps:
Method 1:
Equip a 250mL four-necked flask with a mechanical stirrer (or magnet), a spherical condenser tube and a thermometer. Add 93.0g (1mol) 4-methylpyridine, 6.0g paraformaldehyde, 3.0g triethylamine, 4.5g water (when examining the influence of different proportions of raw materials, the amount of catalyst and solvent, the amount of 4-methylpyridine constant). Heat the oil bath at 130°C and maintain the reaction at 100~108°C for 40h. After the reaction is completed, the reaction solution is distilled under reduced pressure (0~0.01MPa) at 90°C for 6 hours, excess 4-methylpyridine and water are recovered (recyclable), and the residue in the four-neck bottle is collected to obtain (S)- 4-Hydroxyethylpyridine product (if the purity is not enough, it can be washed with an appropriate amount of water and then distilled under reduced pressure) 8.2g, with a single-pass yield of 85.2% (based on the consumed 4-methylpyridine). Tested by gas chromatography and moisture tester, the product contains 99.3% main content and 0.025% moisture.
Experimental principle for the preparation of (S)-4-hydroxyethylpyridine
This reaction is a typical nucleophilic addition reaction. 4-methylpyridine is used as a nucleophile to react with formaldehyde in the lithium carbonate addition reaction. This reaction can use acids and bases as catalysts. It may be that under alkaline conditions, the carbanion generated by α-H of 4-methylpyridine under the action of a strong base has the following resonance structure. The electronegativity of N is greater than that of C. The negative charge is on N, and the resonance mode is more stable. The anion at the α position of 4-methylpyridine is more stable than the anion at the α position of 3-methylpyridine, and is less alkaline, while the conjugate acid is more acidic. In this case, it will be easier to react with formaldehyde; while the O in formaldehyde Slightly electronegative, under acidic conditions, it is easy to form C positive ions with H+ first, and then react with 4-methylpyridine. Therefore, both acidic and alkaline catalysts can promote the reaction. On the other hand, this reaction is a reversible reaction, and many factors during the reaction process will affect the reaction balance. This reaction is an endothermic reaction, and increasing the temperature is beneficial to the progress of the reaction. Due to the participation of water and the sublimation of paraformaldehyde in the reaction, it is difficult to increase the temperature after reaching the azeotropic point. Therefore, the oil bath temperature is generally controlled between 120~130°C, and the actual reaction temperature is generally around 100~108°C.
Method 2:
Preparation of (S)-4-hydroxyethylpyridine (1) Synthesis of (S)-4-hydroxyethylpyridine
Add a certain amount of 4-methylpyridine and paraformaldehyde into the synthesis kettle, and carry out the reaction at normal pressure and temperature of 105-110°C for 45-70 hours. The conversion rate is 40-60%. The crude synthetic product enters the recovery kettle first. , turn on the steam heating of the recovery kettle jacket, control the temperature at 114-116°C for condensation recovery, and remove the generated 2-hydroxyethylpyridine.�Picoline product kettle, unreacted 2-methylpyridine and paraformaldehyde are withdrawn into the condensation kettle and recycled until the reaction efficiency reaches 95%. The recovery process of 2-hydroxyethylpyridine will volatilize to produce 2-methylpyridine and 2-hydroxyethylpyridine. After condensation with three-stage circulating water and deep condensation and liquefaction with cold brine, they are stored in the tail gas recovery tank. The remaining non-condensable gas is adsorbed by activated carbon. Device handling
Preparation of (S)-4-hydroxyethylpyridine (2) Dehydration reaction
Add dehydrating agent NaOH, polymerization inhibitor TBC and water into the dehydration kettle, stir and gradually heat up to 180°C, add (S)-4-hydroxyethylpyridine dropwise, under the condition of dehydrating agent NaOH, 4-hydroxyethylpyridine The dehydration of (S)-4-hydroxyethylpyridine produces 4-vinylpyridine and water. The polymerization inhibitor TBC prevents the self-polymerization of (S)-4-hydroxyethylpyridine. The dehydration reaction efficiency is calculated as 80%. The kettle liquid is mainly 4-vinylpyridine and ( S)-4-hydroxyethylpyridine mixed liquid is condensed with three-stage circulating water and deeply condensed and liquefied with cold brine before being removed from the distillation kettle.
Preparation of (S)-4-hydroxyethylpyridine (3) Refined distillation
The kettle liquid in the rectifying kettle first undergoes 100°C vacuum distillation to distill out the waste water, then passes through 117°C vacuum distillation to evaporate and collect (S)-4-hydroxyethylpyridine, and finally passes through 170°C vacuum distillation. Distill (S)-4-hydroxyethylpyridine to obtain the finished product. During the crude product recovery and product receiving process, volatile materials are condensed by three-stage circulating water and deeply condensed with cold brine, and then stored in recovery tanks for use.
