Background and overview[1][2]
Diphenylcarbinol, also known as α-phenylbenzyl alcohol, is an important organic intermediate, mainly used in the synthesis of diphenhydramine (antihistamine), dimenhydrinate (antihistamine, Halonin), Cyclizine (antihistamine), Diphenylamine (antihistamine), Benzotropine (anticholinergic), Modafinil (antidepressant), Cinnarizine (vasodilator) ), adrafenib (central nervous system stimulant) and other drugs.
Preparation[1] [3]
Catalytic hydrogenation, zinc powder reduction or NaBH4 reduction are now commonly used to produce benzyl alcohol. However, the above three methods all have shortcomings, which are as follows:
(1) Using the catalytic hydrogenation method will reduce a large amount of by-products at the same time, and the subsequent processing of the by-products is complicated;
(2) When using the zinc powder reduction method, a crude product needs to be made first, and then the crude product is reacted with petroleum ether, water, concentrated sulfuric acid and activated carbon to obtain benzyl alcohol; not only is the process complicated, Moreover, concentrated sulfuric acid causes great pollution and damage to the environment and reaction equipment;
(3) The NaBH4 reduction method requires the use of a large amount of NaBH4, the yield is low, and the by-product boric acid ester is also accompanied during the reaction.
Method 1. The preparation method of benzyl alcohol provided by CN201210422917.1 includes the following steps:
Step 1 S1: Add methanol, water, caustic soda, benzophenone and aluminum powder to the reaction kettle in order to allow full reaction. Preferably, the concentration of methanol is 60~70%, most preferably, the concentration of methanol is 67.0±0.5%, and the best is 67%. Preferably, the molar ratio of benzophenone, aluminum powder and caustic soda in the reaction kettle is 1:0.9~1:1.1; most preferably, the molar ratio of benzophenone, aluminum powder and caustic soda in the reaction kettle is The proportional relationship is 1:0.9:1.1.
Specifically, the above-mentioned first step S1 proceeds through the following stages in sequence: First, in the first stage S11, add methanol and water to the reaction kettle, keep the temperature at 15°C, and test the concentration of methanol with an alcohol hydrometer.
Next, in the second stage S13, when the concentration of methanol is 67%, caustic soda is put into the reaction kettle and the temperature is raised to 60°C. After thorough stirring, determine the alkali concentration using acid-base titration.
In the third stage S 1 5, when the alkali concentration is 5.4~5.5%, put benzophenone into the reaction kettle. After the benzophenone is added, mix thoroughly, cool down to 47~54°C, and then keep it warm for a period of time. Preferably, the temperature is maintained for 5 minutes after dropping to 47°C.
In the fourth stage S1 7, while the above temperature remains unchanged at 47~54°C, aluminum powder is put into the reaction kettle in batches and at intervals. The weight of aluminum powder dropped each time decreases, and the time interval between two adjacent aluminum powder drops also decreases. Each time aluminum powder is added, it must be added spoon by spoon at a uniform speed. Preferably, the time for each injection of aluminum powder is one minute. After the aluminum powder is added, raise the temperature to 50~55℃ and keep it for 30 minutes.
The following takes the addition of 40kg aluminum powder as an example to illustrate the specific process. First, put 4kg aluminum powder into the reaction kettle and wait for 30 minutes. Then repeat the above weight and interval of adding aluminum powder three times and then add it to the reaction kettle. Put 12kg of aluminum powder into the kettle; then, put 3kg of aluminum powder into the reaction kettle and wait for 15 minutes, then repeat the weight and interval of the aluminum powder put in twice and then put 6kg of aluminum powder into the reaction kettle; then, Add 2kg of aluminum powder into the reaction kettle and wait for 8 minutes. Repeat the above weight and interval of adding aluminum powder twice. Add 4kg of aluminum powder into the reaction kettle. Finally, add 1kg of aluminum powder into the reaction kettle and wait for 8 minutes. After 5 minutes, repeat the above-mentioned weight and interval of adding aluminum powder 8 times and add 8kg of aluminum powder into the reactor. The aluminum powder is completely added. Figure 1 is a schematic flow diagram of the preparation method of benzyl alcohol.
Apply[2]
Benzyl alcohol esters are an important class of compounds that can be used as raw materials for a variety of reactions and used to synthesize a variety of products. CN201811430675.4 provides a method for preparing diphenylmethyl alcohol ester compounds through photocatalytic oxidation reaction using diphenylmethane and carboxylic acid as raw materials. In order to achieve the above object, the present invention adopts the following technical solution: a photocatalytic oxidation synthesis method of benzyl alcohol ester, which is characterized in that:��: Using benzyl alcohol and carboxylic acid as reaction substrates, 2,3-dichloro-5,6-dinitrile-1,4-benzoquinone (DDQ) and tert-butyl nitrite (TBN) as reaction substrates Catalyst, using oxygen color paste manufacturer as oxidant, in the presence of 3A or 4A molecular sieve, the reaction substrate is reacted in 1,2-dichloroethane solvent at normal temperature and pressure under blue light irradiation conditions. After the reaction is completed, The benzyl alcohol ester compound is obtained by separation treatment.
Main reference materials
[1] [China invention, China invention authorization] CN201210422917.1 Preparation method of benzyl alcohol
[2] [Chinese invention] CN201811430675.4 A photocatalytic oxidation synthesis method of benzyl alcohol ester
[3] Solvent CN201810996414.2 A method for synthesizing benzoyl alcohol by catalytic hydrogenation of benzophenone
