A simple method for preparing benzyl ether

Abstract

The present invention discloses a simple method for preparing benzyl ether using benzyl halide as a raw material in the presence of samarium metal, a small amount of iodine, and paraformaldehyde in N,N-dimethylacetamide. The benzyl halide and paraformaldehyde are added to the N,N-dimethylacetamide under stirring, followed by the addition of samarium metal powder and iodine. The reaction system is carried out under anhydrous conditions. Stirring is performed at 80°C until the reaction is complete. The resulting reaction mixture is subjected to solvent recovery. The crude product is separated and purified by column chromatography to obtain the benzyl ether in a yield of 60-90%.

Description

Technical Field

[0001] The invention belongs to the field of organic chemical synthesis, and particularly relates to a method for synthesizing benzyl ether from benzyl halide in one step by promoting the use of metal samarium in the presence of paraformaldehyde in N,N-dimethylacetamide. Background Art

[0002] Benzyl ether is a widely used fine chemical product and an important intermediate in organic synthesis and the production of fine chemicals such as pharmaceuticals, daily chemicals, and surfactants. Because it has a rose-like mushroom aroma and a woody-citrus aroma, it is often used in soaps, detergents, candies, baked goods, and chewing gum [Reference 1. He Jian; Sun Baoguo. Flavor Chemistry and Technology: Natural, Synthetic, and Blended Flavors. Beijing: Chemical Industry Press, 1995, 127-128]. In addition, it can also be used as a coating plasticizer and a modifier for rubber and latex [Reference 2. Wei Wende. Encyclopedia of Organic Chemical Raw Materials. Beijing: Chemical Industry Press, 1999, 555-559].

[0003] There are two main types of benzyl ether synthesis methods reported so far: the first type is the benzyl alcohol dehydration method. For example, the classic acid-catalyzed dehydration condensation method for benzyl alcohol to synthesize ethers [Reference 3. Zhou Keyan; Lv Junmin. Organic Chemistry Experiments. 2nd Edition. Beijing: Higher Education Press, 1984, 60]; the direct dehydration of benzyl alcohol to synthesize benzyl ethers under microwave irradiation [Reference 4. Li Pigao. Petrochemical Engineering, 2007, 36(5), 489-491], and the iodine-catalyzed dehydration method for benzyl alcohol [Reference 5. Jin Xueyong; Xia Min. Journal of Linyi Normal University, 2004, 26(6), 52-53], etc. The second type is the Williamson method for synthesizing ethers and its derivative technologies. For example, the traditional Williamson synthesis method [Reference 6. Gong, J.; Tadaatsu, J.; Shigeo G. Catal Today, 2003, 79-80, 471-478. Reference 7 Fan Nengting. Organic Synthesis Dictionary. Beijing: Beijing Institute of Technology Press, 1992, 270]; the Williamson method using phase transfer catalysis [Reference 8. Li Jiguo; Sun Shuguang; Zhang Zheng. Chemical Reagents, 1986, 8(6), 370-372]. In addition, the direct generation of benzyl ethers by benzyl halides under the action of strong bases and other reagents often undergoes hydrolysis during the process, which can also be regarded as a broad Williamson method [Reference 9. Jiang, Honglai; et al. China, CN105924328A2016-09-0].

[0004] These synthetic methods utilize different raw materials, methods, and reaction routes, requiring different conditions and environments. While they have applications in chemical production and organic synthesis, they also suffer from common limitations, including equipment corrosion, severe environmental pollution, high product costs, insufficient raw materials, and lengthy reaction steps, which increase process costs. Methods for synthesizing benzyl ethers using benzyl halides as single raw materials offer advantages such as simple procedures, minimal equipment requirements, and readily available raw materials. However, these methods typically require reagents such as strong bases and are carried out in aqueous media. The one-step synthesis of benzyl ethers from benzyl halides under anhydrous conditions has been rarely reported.

[0005] Samarium is a rare earth element. Since its introduction into organic synthesis in 1980 by French chemist Kagan, samarium diiodide has been widely used in organic synthesis. As a reductive coupling reagent, it can promote a wide range of chemical reactions and functional group transformations and has been successfully applied to the synthesis of numerous natural products [Reference 10. Szostak, M.; Fazakerley, N.J.; Parmar, D.; et al., Chemical Reviews, 2014, 114, 5959-6039]. However, samarium diiodide has some drawbacks in its use. For example, it is very sensitive to air, making long-term storage difficult and requiring it to be prepared on the spot. Furthermore, as a single-electron transfer reagent, samarium diiodide only utilizes one electron during use. These factors limit its application in large-scale preparations. In comparison, metallic samarium is more stable in air, easier to handle, relatively inexpensive, and allows for more efficient use of electrons. Therefore, the direct use of metallic samarium in organic synthesis holds greater promise. my country is rich in rare earth resources, with reserves ranking first in the world. The development and utilization of rare earth resources are of great significance.

[0006] The invention discloses a method for preparing a benzyl ether compound by using N,N-dimethylacetamide (DMA) as a solvent and using metal samarium in the presence of a small amount of iodine to directly promote the next step reaction of benzyl halide in the presence of paraformaldehyde in an anhydrous manner. This method has not been reported in domestic and foreign literature. Summary of the Invention

[0007] The purpose of the present invention is to provide a simple method for preparing benzyl ether under anhydrous conditions by using benzyl halide with N,N-dimethylacetamide as solvent in the presence of metal samarium, paraformaldehyde and a small amount of iodine.

[0008] The technical solutions of the present invention are as follows:

[0009] In the presence of a small amount of iodine, benzyl halide and paraformaldehyde are coupled to benzyl ether using samarium metal under mild conditions in N,N-dimethylacetamide. The general reaction formula is shown below:

[0010]

[0011] Where, X=Cl,Br,I

[0012] The technical solution of the present invention is as follows: benzyl halide and paraformaldehyde are added to N,N-dimethylacetamide that has been previously dehydrated and dried under stirring, and then samarium metal powder and iodine are added in sequence. The molar ratio of samarium powder is 0.5-5 times that of the benzyl halide; the molar ratio of paraformaldehyde is 0.5-5 times that of the benzyl halide; the molar ratio of iodine is 0.1-1 times that of samarium powder; and the molar ratio of N,N-dimethylacetamide is 5-50 times that of the benzyl halide. The reaction system is carried out under anhydrous conditions.

[0013] The temperature was slowly raised to 80°C with stirring until the reaction was complete. The obtained reaction mixture was subjected to solvent recovery, and the residue was post-treated and separated by chromatographic column to obtain pure benzyl ether with a yield of 60-90%.

[0014] The advantages and positive effects of the present invention are as follows: the present invention carries out the reaction under anhydrous conditions, and can synthesize benzyl ether from benzyl halide without an additional hydrolysis step, and has unique applicability, especially in anhydrous systems; the present invention has a simple synthesis route, and can obtain benzyl ether through a one-step reaction, with fewer operation steps and no need to separate intermediates, thereby greatly simplifying the operation requirements; the reaction conditions of the present invention are easy to achieve, and special requirements such as strong alkali, strong corrosion, light, and biocatalysis are avoided; the raw materials of the present invention are simple and easy to obtain, and only a single raw material, benzyl halide, is used, and the cost is low. It is a basic chemical product and is easy to obtain; the metal samarium used in the present invention is a rare earth metal, and my country's rare earth resources rank first in the world, so the effective development and utilization of rare earth metals is of great significance to my country; the solvent N,N-dimethylacetamide used in the present invention can be fully recycled and reused, thereby further reducing the reaction cost. DETAILED DESCRIPTION

[0015] The following synthetic examples are used to further illustrate the present invention but are not intended to limit the present invention.

[0016] Example 1

[0017] Benzyl bromide (0.5 mL) and paraformaldehyde (0.3 g) were mixed in pre-dried N,N-dimethylacetamide (5 mL) under magnetic stirring. Samarium powder (0.3 g, 2 mmol) and I2 (0.05 g, 0.2 mmol) were added sequentially under stirring. The temperature was slowly raised to 80°C and the reaction was continued for 4 h. Dilute hydrochloric acid (1 mol·L) was added to quench the reaction. -1 The reaction mixture was post-treated to obtain a crude product, which was then further purified by column chromatography to obtain benzyl ether in a yield of 83%.

[0018] Colorless oil: 1H NMR (500MHz, Chloroform-d) δ7.36 (m, 10H), 4.60 (s, 4H).

[0019] Example 2

[0020] According to the method of Example 1, benzyl chloride was used instead of benzyl bromide to obtain benzyl ether with a yield of 72%.

Claims

1. A simple method for synthesizing benzyl ether, the preparation process of which comprises the following steps: Benzyl halide and paraformaldehyde are mixed uniformly in N,N-dimethylacetamide that has been previously dehydrated and dried under stirring, and then metal samarium powder and iodine are added in sequence. The mixture is stirred at a certain temperature until the reaction is complete. The resulting reaction mixture is subjected to solvent recovery, and the residue is post-treated and separated by a chromatographic column to obtain pure benzyl ether.

2. a simple method for synthesizing benzyl ether according to claim 1, is characterized in that The molar ratio of samarium powder used is 0.5-5 times that of benzyl halide; the molar ratio of paraformaldehyde used is 0.5-5 times that of benzyl halide; the molar ratio of iodine used is 0.05-0.5 times that of samarium powder; and the molar ratio of N,N-dimethylacetamide used is 5-50 times that of benzyl halide.

3. A simple method for synthesizing benzyl ether according to claim 1, characterized in that The benzyl halide used is one or more of benzyl chloride, benzyl bromide and benzyl iodine.

4. A simple method for synthesizing benzyl ether according to claim 1, characterized in that The reaction is a one-pot anhydrous reaction, the reaction solvent can be recovered, and the reaction yield is 60-90%.

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