One-step synthesis method of catechinic aldehyde

Abstract

The invention relates to a one-step synthesis method of catechin. In particular to a synthetic method of 3, 4-dihydroxy benzaldehyde (catechinic aldehyde) which is an important drug and perfume intermediate. According to the invention, catechol is taken as a main raw material, and is reacted with phosphorus oxychloride (POCl3) and dimethylformamide (DMF), so that the product catechin is obtained through one-step aldehyde group addition. The method is simple in step, high in product yield and low in production cost, and has remarkable advantages in industry.

Description

Technical Field

[0001] The invention relates to the field of organic synthesis, and in particular to a one-step synthesis method of catechin aldehyde. Background Art

[0002] Catechinaldehyde is an important intermediate for the synthesis of drugs and spices. As a drug, it can treat diabetic complications. The source of catechinaldehyde in my country mainly relies on imports. There are many methods reported in the literature on the synthesis of catechinaldehyde. The most widely used method is to use catechol as the starting material, methylate it to generate o-methoxyphenol, and then react with glyoxylic acid through condensation and oxidative decarboxylation to generate 3-methoxy-4-hydroxybenzaldehyde, and finally hydrolyze the methyl group at the 3rd position to generate catechinaldehyde. This route is more complicated, and the methyl introduced from the raw material is eventually hydrolyzed, which is equivalent to adding an extra reaction step and increasing the cost. Using copper chloride as the oxidant, the condensation product of catechol and glyoxylic acid is oxidized to catechinaldehyde, and the oxidation yield is about 67.3%, but the amount of copper chloride used is 6 times that of the reactant, the cost is high, and it is difficult to recycle and reuse, which is easy to cause pollution. Summary of the invention

[0003] In order to solve the above technical problems, the present invention provides a one-step synthesis method of catechin aldehyde. The present invention uses catechol as a raw material, reacts with POCl3 and DMF, and obtains the product catechin aldehyde by one step.

[0004] Among them, the specific reaction and reaction conditions are as follows:

[0005]

[0006] Catechol:DMF=1:1-3 (mol), POCl3:DMF=1:1-3 (mol), reaction time 1-5h, reaction temperature 5-100°C.

[0007] The technical solution of the present invention is as follows:

[0008] A one-step synthesis method of catechin aldehyde comprises the following steps: mixing catechol and phosphorus oxychloride (POCl3), dropping dimethylformamide (DMF), then, reacting at a temperature of 5-100°C for a reaction time of 1-5h, and obtaining catechin aldehyde after the reaction is complete;

[0009] Wherein, the molar ratio of catechol, phosphorus oxychloride (POCl3) and dimethylformamide (DMF) is 1:1:1-3.

[0010] Preferably, the reaction temperature is between 20-60°C.

[0011] Preferably, catechol:POCl3:DMF=1:1:2 (mol).

[0012] Beneficial Effects

[0013] The invention uses catechol as a raw material, and reacts with POCl3 and DMF to obtain an aldehyde group in one step to obtain a product. The process is simple, the yield is high, the manufacturing cost is low, and the product has significant advantages in industry.

[0014] Compared with the defects of the prior art such as complex reactions and many by-products, the synthesis method of the present invention has fewer by-products and a one-step synthesis, which not only reduces the cost but is also pollution-free and more environmentally friendly and feasible. DETAILED DESCRIPTION

[0015] The principles and features of the present invention are described below. The examples given are only used to explain the present invention and are not used to limit the scope of the present invention.

[0016] Example 1

[0017] Weigh 15g of catechol and 30mL of DMF and add them into a 250mL three-necked flask, add 23mL of POCl3 dropwise at 0℃ for 1h, heat to 40℃ for reaction for 2h, then heat to 60℃ for reaction for 3h, pour into ice water, add 10w% NaOH aqueous solution to adjust the pH of the solution to neutral, filter, wash with water, and dry to obtain 16.7g of white solid catechin aldehyde with a yield of 89.0%.

[0018] Example 2

[0019] Weigh 15g of catechol and 30mL of DMF and add them into a 250mL three-necked flask, add 23mL of POCl3 dropwise at 5℃ for 1h, heat to 50℃ for reaction for 2h, then heat to 80℃ for reaction for 2h, pour into ice water, add 10w% NaOH aqueous solution to adjust the pH of the solution to neutral, filter, wash with water, and dry to obtain 16.0g of white solid catechin aldehyde with a yield of 85.3%.

[0020] Example 3

[0021] Add 10mL of dichloromethane (DCM) and 7.2g of POCl3 to a three-necked flask in sequence, then drop the pre-mixed 2.7mL of DMF + 10mL of dichloroethane mixture into the three-necked flask at 10°C and within 45min to obtain reagent A; mix 5.0g of catechol and 10mL of dichloroethane to obtain reagent B; drop reagent A into reagent B for 40min, keep the temperature at 5°C, after the drop is complete, raise the temperature to 25°C and continue the reaction for 1.5h to obtain product C; drop product C into 50mL of water for 35min, keep the temperature at 10°C to obtain product D. Add 20mL of dichloroethane to extract and separate D to obtain 5.7g of catechin aldehyde with a yield of 92%.

[0022] Example 4

[0023] Add 10mL of dichloroethane and 7.5g of POCl3 to a three-necked flask in sequence, then drop the pre-mixed 3.0mL of DMF+10mL of dichloroethane mixture into the three-necked flask at 10°C and within 45min to obtain reagent A; mix 5.0g of catechol and 10mL of dichloroethane to obtain reagent B; drop reagent A into reagent B for 40min, keep the temperature at 5°C, after the drop is complete, raise the temperature to 40°C and continue the reaction for 1.5h to obtain product C; drop product C into 50mL of water for 35min, keep the temperature at 10°C to obtain product D. Add 20mL of dichloroethane to extract and separate D to obtain 5.8g of catechin aldehyde with a yield of 94%.

[0024] The above test data show that the present invention uses catechol as a raw material, and obtains a product by reacting with POCl3 and DMF in one step to form an aldehyde group, which has simple steps, high yield and low manufacturing cost. Moreover, compared with the defects of the prior art such as complex reaction and many by-products, the synthesis method of the present invention has few by-products and one-step synthesis, which not only reduces the cost, but also is pollution-free, more green and feasible, and has significant advantages in industry.

[0025] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A one-step synthesis method of catechin aldehyde, characterized in that: Catechol and phosphorus oxychloride (POCl3) are mixed, dimethylformamide (DMF) is added dropwise, and then the reaction temperature is 5-100°C, the reaction time is 1-5h, and catechol aldehyde is obtained after the reaction is complete; Among them, the molar ratio of catechol, phosphorus oxychloride (POCl3) and dimethylformamide (DMF) is 1:1:1~3.

2. The synthesis method according to claim 1, characterized in that: The reaction temperature is between 20-60°C.

3. The synthesis method according to claim 1, characterized in that: The molar ratio of catechol:POCl3:DMF is 1:1:2.

Images