Preparation method of alpha-(2,4-dichlorophenyl)-1h-imidazole-1-ethanol

Abstract

The invention discloses a preparation method of alpha-(2,4-dichlorophenyl)-1h-imidazole-1-ethanol, and belongs to the technical field of organic synthesis. The method comprises the following steps that 1-(2,4-dichlorophenyl)-2-chloroethanol and imidazole are used as raw materials, hexafluoroisopropanol is used as a solvent, an inorganic carrier KOH / A12O3 is used as an alkaline catalyst, and through N-alkylation reaction, filtering, rotary evaporation, neutralization, filtering and recrystallization, the alpha-(2,4-dichlorophenyl)-1h-imidazole-1-ethanol is obtained. According to the preparationmethod of the alpha-(2,4-dichlorophenyl)-1h-imidazole-1-ethanol, reaction conditions are mild, reaction time is short, the solvent is easy to recover, the catalyst and the imidazole which does not participate in the reaction completely can be recycled, and the preparation method of the alpha-(2,4-dichlorophenyl)-1h-imidazole-1-ethanol is a green technology for synthesizing the alpha-(2,4-dichlorophenyl)-1h-imidazole-1-ethanol.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a preparation method of imidazole ethanol. Background technique [0002] Imidazole ethanol, the chemical name is a-(2,4-dichlorophenyl)-1H-imidazole-1-ethanol, and the English name is alpha-(2,4-Dichlorophenyl)-1H-imidazole-1-ethanol. White to pink crystal, insoluble in water, soluble in ethanol and other organic solvents, is an important intermediate for the synthesis of imidazole antifungal drugs such as econazole, miconazole and fruit preservatives. [0003] The synthetic method of imidazole ethanol has multiple, and the production technology commonly used in industry is as follows at present: Wang Yu etc. obtain imidazole ethanol with 2,4-dichlorophenyl oxirane and imidazole reaction under alkaline conditions, and the reaction used There are many reagents, which cause more pollution of three wastes; Wang Minghui et al. use tetrabutylammonium bromide (TB...

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Problems solved by technology

[0003] The synthetic method of imidazole ethanol has multiple, and the production technology commonly used in industry is as follows at present: Wang Yu etc. obtain imidazole ethanol with 2,4-dichlorophenyl oxirane and imidazole reaction under alkaline conditions, and the reaction used There are many reagents, which cause more pollution of three wastes; Wang Minghui et al. use tetrabutylammonium bromide (TBAB), polyethylene glycol 400 (PEG400) as catalyst, tetrahydrofuran (THF) or acetone as organic solvent, by reducing product and imidazole Carry out N-alkylation reaction in the presence of sodium hydroxide (NaOH) to synthesize imidazole ethanol, because THF is easy to become peroxide during storage, long-term exposure will cause great damage to the blood, cause chronic poisoning, and cause Neurasthenic Syndrome; Liao Yongwei et al. used tetrabutylammonium bromide as a catalyst, N,N-dimethylformamide (DMF) as an organic solvent, and synthesized it by N-alkylation reaction of reduced product and imidazole in the presence of NaOH Imidazole ethanol, the imidazole ethanol obtained by this process has a low melting point, only 113-114.5°C. In addition, DMF is unstable in the presence of NaOH strong base (especially at high temperature), and is easily hydrolyzed into formic acid and dimethylamine, resulting in DMF Recycling is difficult, and the price of DMF is expensive, which affects the quality of the product and also increases the cost of synthesis; Li Jinmei et al. use reducing substances and imidazole as raw materials, use DMF or toluene as solvents, and use powdered sodium hydroxide or powdered potassium hydroxide or The lye is used as a catalyst, and benzyltriethylammonium chloride (TEBA) or organic ammonium or tetrabutylammonium iodide or PEG600 is used as a phase transfer catalyst to carry out N-alkylation reaction to synthesize imidazole ethanol, and the reaction time of this process is long , the reaction temperature is high, the operation is complicated, and energy is wasted

[0004] Although the above-mentioned imidazole ethanol synthesis has been improved to a certain extent, the reaction is generally carried out in an aqueous alkali solution, and the yield is low. Since condensation in an aqueous solution is a liquid-liquid heterogeneous catalytic reaction, in order to increase the yield, a phase transfer catalyst is added. The cost of phase transfer catalyst is high, it cannot be recycled and reused, and it will also pollute the environment; in addition, increasing the temperature can increase the yield, but as the reaction temperature increases, the side reactions also increase, affecting the increase in yield; reaction The imidazoles used in the production process are expensive, excessive use, can not be recycled, pollute the environment and also increase the cost

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