A method for synthesizing alpha-alkoxyl p-chlorobenzyl phosphate

Abstract

The application provides a synthesis method of alpha-alkoxyl p-chlorobenzyl phosphate. The synthesis method adopts p-chlorobenzylidene dichloride (I) and phosphite (II) as raw materials, and alpha-alkoxyl p-chlorobenzyl phosphate (III) is obtained through one-step condensation under the condition of sodium alcoholate. The process method has the advantages of cheap and easily available raw materials, high yield, low cost, mild reaction condition and suitability for industrial scale production.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and specifically to a method for synthesizing α-alkoxy-p-chlorobenzyl phosphate. Background Technology

[0002] α-Alkoxy-p-chlorobenzyl phosphate is an important intermediate in the synthesis of the fungicide cyproconazole, and its molecular structure is shown below:

[0003]

[0004] Existing intermediate synthesis processes suffer from numerous problems, including complex procedures, the scarcity and unavailability of raw materials or intermediates, high raw material costs, and difficulties in industrial-scale production. For example, the synthesis methods reported in patents CN106279264 and CN106279275, which use p-chlorobenzaldehyde dimethyl acetal and triethyl phosphite or dimethyl diphosphate as raw materials, suffer from issues such as the difficulty in obtaining raw materials and demanding catalyst preparation conditions. The preparation of p-chlorobenzaldehyde dimethyl acetal involves dehydrating p-chlorobenzaldehyde and methanol under reflux dehydration conditions, which is costly, energy-intensive, and ultimately results in high product costs.

[0005] Therefore, the focus of research in this field is to find a simple and smooth process for synthesizing α-alkoxy-p-chlorobenzyl phosphate that uses inexpensive and readily available raw materials, has low cost, and is suitable for industrial-scale production. Summary of the Invention

[0006] The purpose of this invention is to overcome the above-mentioned shortcomings and, based on existing technology, provide a method for synthesizing α-alkoxy-p-chlorobenzyl phosphate. This method uses inexpensive and readily available raw materials, has low cost, and operates under mild reaction conditions. Compared with other reported synthesis methods, this invention uses p-chlorobenzyl dichloride and phosphite as raw materials. The raw materials are inexpensive and readily available; p-chlorobenzaldehyde is obtained by hydrolyzing p-chlorobenzyl dichloride. The synthesis method of this invention directly uses p-chlorobenzyl dichloride as a raw material, eliminating the need for the hydrolysis of p-chlorobenzyl dichloride to prepare aldehydes, followed by reflux dehydration to prepare acetals, etc., greatly reducing raw material costs and simplifying the process, making it suitable for industrial-scale production.

[0007] This invention provides a method for synthesizing α-alkoxy-p-chlorobenzyl phosphate, characterized in that the method uses p-chlorobenzylidene dichloro(I) and phosphite (II) as raw materials, and condenses them in one step under sodium alkoxide conditions to obtain α-alkoxy-p-chlorobenzyl phosphate (III). The synthetic route is as follows:

[0008]

[0009] In the formula, R1 is methyl or ethyl; R2 is a C1-C4 alkyl group.

[0010] According to the above synthesis method, R1 is methyl or ethyl, preferably methyl.

[0011] According to the above synthesis method, R2 is a C1-C4 alkyl group, preferably methyl or ethyl.

[0012] According to the above synthesis method, the sodium alkoxide mentioned in the condensation reaction is sodium methoxide or sodium ethoxide, more preferably sodium methoxide.

[0013] According to the above synthesis method, the solvent for the condensation reaction is selected from one or more of methanol, ethanol, n-propanol, isopropanol, and n-butanol, or a mixture of one or more of the aforementioned solvents with a non-polar solvent such as benzene, toluene, or xylene, with methanol being preferred.

[0014] According to the above synthesis method, in the condensation reaction, the molar ratio of p-chlorobenzyl dichloro, phosphite and sodium alkoxide is 1.0:1.0–1.3:2.0–3.0; the reaction temperature is 0℃–50℃, preferably the molar ratio is 1.0:1.0:2.0, and the reaction temperature is preferably 0–10℃.

[0015] Compared with the synthesis processes provided in the prior art, the production process described in this invention has the following advantages:

[0016] 1) Using p-chlorobenzyl dichloro and phosphite as raw materials, condensation under sodium alkoxide conditions yields α-alkoxy p-chlorobenzyl phosphate with the structure of formula (Ⅲ), which greatly reduces raw material costs and simplifies the process.

[0017] 2) The reaction conditions of this invention are mild and suitable for industrial-scale production. Attached Figure Description

[0018] Figure 1 This is a synthetic route diagram of the α-alkoxy-p-chlorobenzyl phosphate of the present invention. Detailed Implementation

[0019] The production process described in this invention will be further described below with reference to specific implementation examples to better understand this invention.

[0020] Example 1

[0021] In a reaction flask, 50.0 g (0.25 mol) of p-chlorobenzyl dichlorophosphate and 27.5 g (0.25 mol) of dimethyl phosphite, along with 150 g of methanol as solvent, were added. The temperature was controlled at 0-10 °C. Sodium methoxide (13.5 g (0.50 mol) was added in portions. After the addition was complete, the mixture was stirred at 0-10 °C for 2 hours. The reaction solution was then subjected to simple post-treatment, filtration, and solvent removal to obtain 65.5 g of α-methoxy-p-chlorobenzyl phosphate with a purity of 96.5% and a yield of 95.6%.

[0022] Example 2

[0023] In a reaction flask, 50.0 g (0.25 mol) of p-chlorobenzyl dichlorophosphate and 34.5 g (0.25 mol) of diethyl phosphite, along with 150 g of methanol as solvent, were added. The temperature was controlled at 0-10 °C. Sodium methoxide (13.5 g (0.50 mol) was added in portions. After the addition was complete, the mixture was stirred at 0-10 °C for 2 h. The reaction solution was then subjected to simple post-treatment, filtration, and solvent removal to obtain 72.4 g of α-methoxy-p-chlorobenzyl phosphate with a purity of 96.1% and a yield of 95.2%.

[0024] Example 3

[0025] In a reaction flask, p-chlorobenzyl dichlorophosphate (50.0 g, 0.25 mol) and dimethyl phosphite (27.5 g, 0.25 mol), along with 150 g of methanol solvent, were added. The temperature was controlled at 0-10 °C. Sodium ethoxide (34.0 g, 0.50 mol) was added in portions. After the addition was complete, the mixture was stirred at 0-10 °C for 2 h. The reaction solution was then subjected to simple post-treatment, filtration, and solvent removal to obtain 68.9 g of α-ethoxy-p-chlorobenzyl phosphate with a purity of 96.2% and a yield of 95.3%.

[0026] Example 4

[0027] In a reaction flask, 50.0 g (0.25 mol) of p-chlorobenzyl dichlorophosphate and 27.5 g (0.25 mol) of dimethyl phosphite were added, along with 75 g of methanol and 75 g of toluene as solvents. The temperature was controlled at 0-10 °C. Sodium methoxide (13.5 g (0.50 mol) was added in portions. After the addition was complete, the mixture was stirred at 0-10 °C for 2 h. The reaction solution was then subjected to simple post-treatment, filtration, and solvent removal to obtain 65.7 g of α-methoxy-p-chlorobenzyl phosphate with a purity of 96.0% and a yield of 95.5%.

[0028] The specific embodiments of the present invention have been described in detail above, but they are merely examples, and the present invention is not limited to the specific embodiments described above. Any equivalent modifications and substitutions to the present invention are also within the scope of the present invention.

Claims

1. A method for synthesizing α-alkoxy-p-chlorobenzyl phosphate, characterized in that, This synthetic method uses p-chlorobenzyl dichloro(I) and phosphite (II) as raw materials, and condenses them in one step under sodium alkoxide conditions to obtain α-alkoxy-p-chlorobenzyl phosphate (III). In the condensation reaction, the molar ratio of p-chlorobenzyl dichloro, phosphite, and sodium alkoxide is 1.0:1.0:2.0; the reaction temperature is 0℃-50℃, and the synthetic route is as follows: In the formula, R1 is methyl or ethyl; R2 is a C1-C4 alkyl group.

2. The synthesis method according to claim 1, characterized in that, R1 is a methyl group.

3. The synthesis method according to claim 1, characterized in that, R2 is methyl or ethyl.

4. The synthesis method according to claim 3, characterized in that, The sodium alkoxide mentioned in the condensation reaction is sodium methoxide.

5. The synthesis method according to claim 1, characterized in that, The solvent for the condensation reaction is selected from one or more of methanol, ethanol, n-propanol, isopropanol, and n-butanol, or a mixture of one or more of the aforementioned solvents with a nonpolar solvent such as benzene, toluene, or xylene.

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