A method for synthesizing aldehydes by silver catalysis under the promotion of metal samarium

Abstract

The present invention discloses a simple method for preparing aldehydes using a halogenated hydrocarbon in N,N-dimethylformamide under the promotion of samarium metal and a silver salt. The halogenated hydrocarbon is added to N,N-dimethylformamide under stirring, followed by the addition of samarium metal powder and silver salt powder. The reaction system is carried out under anhydrous conditions. Stirring is continued at room temperature until the reaction is complete. The resulting reaction mixture is subjected to solvent recovery. The crude product is separated by column chromatography, and the solvent is removed by distillation to obtain the aldehyde in a yield of 60-95%.

Description

Technical Field

[0001] The invention belongs to the field of organic chemical synthesis, and particularly relates to a method for synthesizing aldehydes in one step from halogenated hydrocarbons in N,N-dimethylformamide using silver salt catalysis promoted by metal samarium. Background Art

[0002] Aldehyde compounds have a wide range of applications, whether as solvents, fine chemical products, basic chemical raw materials or organic synthesis reagents. For example, they have extremely important applications in the field of organic synthesis. It is an important method to obtain alcohol structures through catalytic hydrogenation or addition with organometallic reagents. Aldehydes can be reduced to amine compounds through amination [Reference 1. Cantu, DC; Padmaperuma, AB; Nguyen, M.-T.; et al, ACS Catal. 2018, 8(8), 7645-7658l; Reference 2. Irrgang, T.; Kempe, R., Chem. Rev. 2020, 120(17), 9583-9674]. Aldehyde compounds are also widely used in chiral synthesis [Reference 3. Marcum, JS; Meek, SJ, J. Am. Chem. Soc. 2022, 144(42), 19231-19237]. In addition, aldehydes can also be used to prepare alkenes through decarbonylation reactions [Reference 4. Ainembabazi, D.; Reid, C.; Chen, A.; et al, J. Am. Chem. Soc. 2020, 142(2), 696-699].

[0003] There are many methods for preparing aldehyde compounds. Among them, the method of preparing aldehydes by oxidation of alcohol compounds was discovered very early and is still widely studied and applied [Reference 5. Yan, Q.; Fang, Y.C.; Jia, Y.X.; et al., New J. Chem. 2017, 41(6), 2372-2377; Reference 6. Wang, L.-Y.; Li, J.; Lv, Y.; et al., J. Organomet. Chem. 2011, 696(20), 3257-3263]. This method requires equipment with oxidation resistance and usually produces a large amount of industrial waste. Relatively speaking, the formylation strategy of olefins is a relatively common process for preparing aldehyde compounds in chemical production. This method uses transition metal catalysis to formylate olefins with carbon monoxide and hydrogen to produce aldehydes with an additional carbon atom [for example, document 7. Fleischer, I.; Wu, L.; Profir, I.; et al Chem. Eur. J. 2013, 19 (32), 10589-10594]. This process method has less waste discharge during the reaction process, but requires the use of synthesis gas (CO / H2) for gas-phase reaction at a high pressure, which has high requirements for equipment, and the chemical selectivity and regioselectivity of the obtained product are also difficult to control. In addition, aldehydes can also be prepared by the reduction of carboxylic acid derivatives [document 8. Rysak, V.; Descamps-Mandine, A.; Simon, P.; et al, Catal. Sci. Technol. 2018, 8 (14), 3504-3512], etc. These synthetic methods have different raw materials, different methods, and different conditions and environments for the reaction routes. They have been widely used in chemical production and organic synthesis.

[0004] Starting from halogenated hydrocarbons, the reaction of butyl lithium with N,N-disubstituted formamides in the presence of butyl lithium to prepare aldehyde compounds is a relatively unique method. This method involves lithium-halogen exchange between butyl lithium and halogenated hydrocarbons, and further formylation reaction with disubstituted formamides, thereby directly forming an aldehyde group at the halogen position [Reference 9. Gallou, Fabrice; Haenggi, Ruedi; Hirt, Hans; et al, Tetrahedron Lett., 2008, 49(34), 5024-5027]. Since halogenated hydrocarbons are commonly used basic raw materials for organic synthesis, this method has great potential value in application. However, since butyl lithium is extremely sensitive to air and moisture, it is an extremely flammable and explosive dangerous reagent, and the reaction process often requires low temperature, generally at -78°C or lower, resulting in stringent requirements for both the reaction operation process and the storage of reagents, making it difficult to scale up the reaction. Therefore, this method is currently generally only used in laboratory synthesis. Our previous research has found that under the catalysis of cuprous iodide, using halogenated hydrocarbons as raw materials and N,N-methylformamide (DMF) as solvent, with the help of metal samarium reduction, aldehyde compounds can be obtained in high yield under mild conditions [Reference 10. Xiao, S.; Liu, C.; Song, B., et al, Chem. Commun. 2021, 57(50), 6169–6172]. In contrast, this method has mild operating conditions, easy-to-use and easy-to-store reagents, high yield, and good prospects for large-scale preparation. However, this method also has obvious limitations. On the one hand, this method is mainly suitable for the preparation of aromatic aldehydes from halogenated aromatic hydrocarbons and cannot synthesize aliphatic aldehydes, which greatly limits the scope of practical application; on the other hand, the amount of cuprous iodide used is large (molar ratio not less than 10%), and the iodide is relatively expensive, which limits its large-scale use. In addition, the required reaction time is long, at least 4 hours or more, which increases the process cost.

[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. It can facilitate a wide range of chemical reactions and functional group transformations, and has been successfully applied to the synthesis of numerous natural products [Reference 11. Szostak, M.; Fazakerley, N.J.; Parmar, D.; et al., Chem. Rev. 2014, 114, 5959-6039]. However, samarium diiodide has several drawbacks. For example, it is very sensitive to air, making long-term storage difficult and requiring immediate preparation. 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 has rich rare earth resources, accounting for more than 90% of the world's reserves. The development and utilization of rare earth resources is of great significance.

[0006] The present invention discloses a method for preparing aldehyde compounds by using N,N-dimethylformamide (DMF) as a solvent and using metal samarium to directly promote the one-step reaction of halogenated hydrocarbons (including halogenated aliphatic hydrocarbons and halogenated aromatic hydrocarbons) and DMF in the presence of silver bromide (or potassium bromide and silver nitrate). This method has not been reported in domestic and foreign literature. Summary of the Invention

[0007] The object of the present invention is to provide a simple method for preparing aldehyde by using halogenated hydrocarbons in DMF as solvent under the promotion of metal samarium and silver salt.

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

[0009] In the presence of silver salt, samarium metal is used to reduce and couple halogenated hydrocarbons and DMF to aldehydes under mild conditions. The general reaction formula is shown below:

[0010]

[0011] In the formula, X is preferably Br, I; R is preferably alkyl, phenyl; and the silver salt is preferably silver bromide, silver nitrate + sodium bromide, or silver acetate.

[0012] The technical solution of the present invention is as follows: a halogenated hydrocarbon is added to N,N-dimethylformamide that has been previously dehydrated and dried under stirring, and then freshly prepared metal samarium powder and silver salt powder are added in sequence. The molar ratio of the samarium powder is 0.5-5 times that of the halogenated hydrocarbon; the molar ratio of the silver bromide is 0.01-0.05 times that of the samarium powder; and the molar ratio of the N,N-dimethylformamide is 5-50 times that of the halogenated hydrocarbon. The reaction system is carried out under anhydrous conditions.

[0013] The reaction mixture is stirred at room temperature until the reaction is complete. The solvent is recovered from the obtained reaction mixture, and the residue is post-treated and separated by a chromatographic column to obtain the pure aldehyde with a yield of 60-90%.

[0014] The advantages and positive effects of the present invention are as follows: the product obtained by the present invention has a wide range of types and can be used for the synthesis of various aldehyde structures; the synthesis route of the present invention is simple and efficient, and aldehyde can be obtained through a one-step reaction, with fewer operation steps and no need to separate intermediates, which greatly simplifies the operation requirements; the reaction conditions of the present invention are easy to achieve, and the operation can be directly carried out in air, avoiding special requirements such as oxygen-free, low temperature, high temperature, light, and biocatalysis; the raw materials of the present invention are simple and easy to obtain, and the halogenated hydrocarbons used are low in cost and are basic chemical products; the amount of the catalyst silver salt used in the present invention is very small, and only 1% is required to achieve the reaction; 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 aldehyde compounds synthesized by the present invention have a high yield, a simple post-treatment process, and the products are easy to separate during post-treatment; the solvent N,N-dimethylformamide 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] Add 0.3g of freshly prepared samarium metal powder and 0.01g of silver bromide to the reaction vessel in sequence, then add 5mL of anhydrous N,N-dimethylformamide and stir magnetically. Add 0.2mL of bromobenzene. The reaction solution will turn darker in color within 1h at room temperature. Continue the reaction for 2h. Add 5mL of dilute hydrochloric acid (2mol·L -1 ) to terminate the reaction, and the reaction mixture was post-treated to obtain a crude product, which was then further purified by column chromatography to obtain benzaldehyde with a yield of 89%.

[0018] Colorless oil; 1 HNMR(500MHz,Chloroform-d)δ10.02(s,1H),7.88(m,2H),7.63(m,1H),7.53(m,2H)ppm; 13 CNMR(125MHz,Chloroform-d)δ192.4,136.4,134.4,129.7,129.0ppm.

[0019] Example 2

[0020] According to the method of Example 1, sodium bromide and silver nitrate were used instead of silver bromide (equimolar amounts) to obtain benzaldehyde with a yield of 87%.

[0021] Example 3

[0022] According to the method of Example 1, silver acetate was used instead of silver bromide (equimolar amount) to obtain benzaldehyde with a yield of 86%.

[0023] Example 4

[0024] According to the method of Example 1, benzyl bromide was used instead of bromobenzene to obtain phenylacetaldehyde with a yield of 81%.

[0025] Colorless oil; 1 H NMR (500MHz, Chloroform-d) δ9.75 (t, J = 2.5 Hz, 1H), 7.39-7.22 (m, 5 H), 3.69 (d, J = 2.5 Hz, 2 H) ppm; 13 C NMR (125 MHz, Chloroform-d): δ 199.5, 131.8, 129.6, 129.0, 127.4, 50.6 ppm.

Claims

1. A method for synthesizing aldehydes, characterized in that In the presence of silver salt, samarium metal is used to promote the one-step reaction of halogenated hydrocarbons in N,N-dimethylformamide to prepare aldehydes. The preparation process includes the following steps: The halogenated hydrocarbon is mixed uniformly in N,N-dimethylformamide that has been previously dehydrated and dried under stirring at room temperature, and then freshly prepared metal samarium powder and silver salt powder are added in sequence, and stirred at room 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 a pure aldehyde. The halogenated hydrocarbon used is selected from halogenated aliphatic hydrocarbons and halogenated aromatic hydrocarbons; and the silver salt used is selected from silver bromide, silver nitrate + sodium bromide, and silver acetate.

2. A method for synthesizing aldehyde according to claim 1, characterized in that The molar ratio of the samarium powder used is 0.5-5 times that of the halogenated hydrocarbon; the molar ratio of the silver salt used is 0.01-0.05 times that of the samarium powder; and the molar ratio of the N,N-dimethylformamide used is 5-50 times that of the halogenated hydrocarbon.

3. A method for synthesizing aldehyde according to claim 1, characterized in that The halogenated hydrocarbons used are one or more of chlorinated hydrocarbons, brominated hydrocarbons and iodinated hydrocarbons.

4. A method for synthesizing aldehyde according to claim 1, characterized in that The reaction temperature is room temperature, the reaction is a one-pot one-step reaction, the reaction solvent can be recovered, and the reaction yield is 60-90%.

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