Application of 4-benzyloxybenzaldehyde_Kain Industrial Additive

Background and overview^[1][4]

4-Benzyloxybenzaldehyde can be used as an intermediate for pharmaceutical and chemical synthesis. Benzyloxybenzaldehyde is not only a key compound in the synthesis of pectin series drugs, but also an important intermediate in organic synthesis and pharmaceutical industry [1. This compound is an intermediate in the synthesis of the cholesterol absorption inhibitor etimibe (for the treatment of hyperlipidemia). It is also an intermediate in the synthesis of Atenolol, Ifenprodil, Ritodrine, and Bufenol. It is an important raw material for drugs such as Buphenine and Isoxsuprine. At the same time, drugs prepared from this compound can be used to prevent and treat rice blast, wheat scab and other fungi and to kill oncomelania and other snails. The experimental results are very good. It is a highly efficient, low-toxic, broad-spectrum and environmentally compatible drug. Better medicine. The synthesis and process improvement of similar compounds are based on the traditional solvent method, using tetrabutylammonium chloride as the phase transfer catalyst, maintaining alkaline conditions and refluxing for more than 12 hours, and the product yield is about 32% to 71%. There are many impurities, the separation is troublesome, the operation is complicated, and the reaction conditions are difficult to control.

Apply^[1-3]

4-Benzyloxybenzaldehyde can be used as an intermediate for pharmaceutical and chemical synthesis. Examples of its application are as follows:

1. Preparation of 4-benzyloxybenzyl alcohol. 4-Benzyloxybenzyl alcohol is an important organic synthesis intermediate in the pesticide and pharmaceutical industries and is widely used in the pesticide, pharmaceutical and chemical industries. Currently, although there are a variety of industrial methods for synthesizing 4-benzyloxybenzyl alcohol, most of them have the disadvantages of higher costs or lower yields. How to provide a 4-benzyloxy benzyl alcohol with a simple route and high yield? The preparation method of benzyl alcohol is a technical problem that needs to be solved by those skilled in the art. Some studies have provided a method for preparing 4-benzyloxybenzyl alcohol with a simple route and high yield. The specific steps are: A. Add an appropriate amount of dimethylformamide, p-fluorobenzaldehyde, phenol, inorganic Alkali and cuprous salt are stirred and heated, and the temperature is controlled at 100°C to 150°C for reaction. After the reaction is complete, it is cooled to room temperature, filtered to remove the inorganic salt, and then dimethylformamide is recovered. The obtained 4-benzyloxybenzaldehyde is added Dissolve in methanol; B. Add the methanol solution of 4-benzyloxybenzaldehyde and the catalyst into the pressure kettle, control the temperature at 50°C to 70°C, introduce hydrogen for reaction, keep the hydrogen pressure above 5kg/cm2, and the reaction is complete After cooling to room temperature, the catalyst was removed by filtration under anaerobic conditions, methanol was recovered, and the remaining product was cooled and crystallized to obtain 4-benzyloxybenzyl alcohol.

2. Preparation of 3-(4-benzyloxyphenyl)-1-phenyl-3-(p-tolylthio)propan-1-one. This method uses 4-benzyloxybenzaldehyde, acetophenone and 4-methylthiophenol as synthetic raw materials, dissolves them with slight heat, uses zirconium chloride as a catalyst, and performs a condensation reaction at room temperature to prepare 3-( 4-Benzyloxyphenyl)-1-phenyl-3-(p-tolylthio)propan-1-one, its reaction formula is as follows:

It mainly includes the following steps: (1) Add 4-benzyloxybenzaldehyde, acetophenone and 4-methylthiophenol into a dry three-neck flask, stir the mixture to dissolve, then add zirconium chloride, Stir for 1-2 hours and follow the reaction with TLC; (2) When the reaction is completed, add deionized water for shaking and washing, and a light yellow solid will precipitate; (3) Filter out the solid crude product and recrystallize it with absolute ethanol to obtain 3- (4-Benzyloxyphenyl)-1-phenyl-3-(p-tolylthio)propan-1-one. The mass ratio of the reaction raw materials 4-benzyloxybenzaldehyde, acetophenone and 4-methylthiophenol is: 210-220:120-130:120-130; the amount of catalyst zirconium chloride added is The total mass of the material and its mass ratio are: 1:0.07-0.08.

3. Preparation of meso-tetrakis (4-benzyloxyphenyl) porphyrin. Porphyrin compounds have unique structures and properties and have broad application prospects in anti-cancer drugs, catalytic oxidation, optoelectronic materials, analytical chemistry, simulated photochemistry, etc. Chinese and foreign researchers have conducted extensive and in-depth research on them and achieved many scientific research results. . The specific steps are: add 20ml propionic acid, 20ml nitrobenzene and 30ml glacial acetic acid into a 250ml three-necked flask, stir mechanically, heat to 128°C and reflux, add 4.25g (20mmol) of 4-benzyloxybenzaldehyde dropwise in 20ml within 10 minutes. A solution of propionic acid, and then a solution of 1.4 ml of pyrrole (20 mmol) dissolved in 20 ml of glacial acetic acid was added dropwise within 10 min, and heated to reflux for 40 min to obtain a purple-black solution. After the solution is cooled, evaporate nearly half of the solvent under reduced pressure, add an equal amount of methanol to the remaining mother liquor, refrigerate overnight, and filter to obtain a bright purple solid. Wash with methanol and water until the filtrate is colorless, and use methylene chloride as the eluent. Silica gel column chromatography was performed to collect the first purple-red color band and dried under vacuum to obtain 1.24g of bright purple crystal meso-tetrakis (4-benzyloxyphenyl) porphyrin (1) (yield 24%).

Preparation ^{[1, 3-4]}

Method 1: Add an appropriate amount of dimethylformamide, p-fluorobenzaldehyde, phenol, inorganic alkali and cuprous salt into the reaction kettle, stir and heat up, and control the temperature at 100°C to 150°C for reaction. After the reaction is complete Cool to room temperature, filter to remove inorganic salts, and then recover dimethylformamide to obtain 4-benzyloxybenzaldehyde.

Method 2: Put 5g (41mmol) of p-hydroxybenzaldehyde and 11.3g of potassium carbonate into a three-necked flask, add 25ml of N,N-dimethylformamide (DMF), stir for 15min to form a suspension, and add benzyl chloride dropwise 5.7g (45mmol), react at room temperature for 6-8 hours, follow the reaction with TLC to the end, pour into the ice-water mixture and immediately precipitate a large amount of solid, filter with suction, wash with water several times, and dry to obtain an off-white solid 4-benzyloxy 8.13g of benzaldehyde (4) (yield 94%).

Method 3: In the reaction flask�Add 1.342g (0.011mol) hydroxybenzaldehyde, 0.59g (0.0105mol) KOH and 10mLDMF in sequence, stir evenly and then add 1.265g (0.01mol) benzyl chloride. React under microwave radiation of a certain power, and visually monitor the amount of target substance produced by combining with TLC (the target substance is too little or carbonized and not separated). It should be completed. After the reaction solution is cooled to room temperature, dissolve it with 30 ml of methylene chloride, and then use Wash with 20% NaOH solution to remove excess phenol, and then wash with distilled water until neutral. The organic phase was dried with anhydrous Na2SO4 overnight and then filtered. The solvent was evaporated to obtain a crude product, which was then recrystallized with an alcohol-water mixed solvent, suction filtered, and dried naturally, then placed in a CaCl2 dryer to dry the product.

Main reference materials

[1] CN201610772408.X Preparation method of 4-benzyloxybenzyl alcohol

[2] CN201510497453.4 A synthesis method of 3-(4-benzyloxyphenyl)-1-phenyl-3-(p-tolylthio)propane-1-one

[3] CN201110251732.4 Synthesis methods of three novel porphyrin compounds containing benzyloxy groups

[4] Optimize the reaction conditions for the synthesis of benzyloxybenzaldehyde