A method for preparing p-nitrobenzaldehyde from p-nitrobenzyl halide

Abstract

The present invention discloses a simple method for preparing p-nitrobenzylaldehyde in N,N-dimethylacetamide using p-nitrobenzyl halide and paraformaldehyde under the promotion of samarium metal and manganese chloride. The p-nitrobenzyl halide and paraformaldehyde are added to N,N-dimethylacetamide under stirring, followed by the addition of samarium metal powder and manganese chloride powder. The reaction system is carried out under anhydrous conditions. Stirring is continued at 80°C until the reaction is complete. The resulting reaction mixture is subjected to solvent recovery. The crude product is separated by column chromatography, the solvent is removed by distillation, and recrystallization is performed to obtain p-nitrobenzaldehyde in a yield of 60-70%.

Description

Technical Field

[0001] The invention belongs to the field of organic chemical synthesis, and particularly relates to a method for synthesizing p-nitrobenzaldehyde in one step by reacting p-nitrobenzyl halide and paraformaldehyde in N,N-dimethylacetamide under the catalysis of manganese salt promoted by a reducing reagent metal samarium. Background Art

[0002] p-Nitrobenzaldehyde is an important intermediate in organic synthesis and the production of fine chemicals such as medicines, dyes, and pesticides. It plays a particularly important role in pharmaceutical synthesis [Reference 1. Ji Lei. (2008). Study on the Synthesis of p-Nitrobenzaldehyde. (Doctoral dissertation), Nanjing University of Science and Technology]. In the doctoral dissertation cited above, several practical applications of p-nitrobenzaldehyde are listed, and traditional synthesis methods for the compound are elaborated in detail, including p-nitrotoluene oxidation, benzyl chloride nitration, hydrolysis, oxidation, etc., which can be found in detail. These synthesis methods use different raw materials, different methods, and different conditions and environments for the reaction routes. They have been widely used in fields such as chemical production and organic synthesis.

[0003] Due to the influence of the nitro group on the benzene ring, the preparation of p-nitrobenzaldehyde cannot usually be achieved by reduction methods using organometallic reagents or carboxylic acid derivatives. Starting from p-nitrobenzyl halide, p-nitrobenzaldehyde can be generated by oxidation, for example, using substituted morpholine nitrogen oxides [Reference 2. Tabata, Masayuki; et al. European Journal of Organic Chemistry (2014), 2014 (16), 3402-3410.], and hydrogen peroxide oxidation reaction under certain conditions [Reference 3. Russell, Glen A.; et al. Journal of Organic Chemistry (1979), 44 (22), 3990-3991]. The reaction conditions of these methods must be carried out in the presence of an oxidant. When reducing conditions or reagents are present in the synthesis route, the oxidation method cannot be used due to the presence of the nitro group. Under reducing conditions such as reducing agents, there are currently few documents that achieve the synthesis of p-nitrobenzyl halide into p-nitrobenzaldehyde.

[0004] 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 4. 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 generally 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 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.

[0005] The present invention discloses a method for preparing a p-nitrobenzaldehyde compound by directly promoting a one-step reaction between p-nitrobenzyl halide and paraformaldehyde using N,N-dimethylacetamide (DMA) as a solvent and a reducing reagent, metal samarium, in the presence of manganese chloride. This method has not been reported in domestic or foreign literature. Summary of the Invention

[0006] The object of the present invention is to provide a simple method for preparing p-nitrobenzaldehyde by using p-nitrobenzyl halide with N,N-dimethylacetamide as solvent under the promotion of metal samarium and manganese chloride.

[0007] The technical solutions of the present invention are as follows:

[0008] In the presence of manganese salt, samarium metal is used to reduce and couple p-nitrobenzyl halide and DMA under mild conditions to form p-nitrobenzaldehyde. The general reaction formula is shown below:

[0009]

[0010] Where, X=Cl,Br,I

[0011] The technical solution of the present invention is as follows: p-nitrobenzyl halide and paraformaldehyde are added to N,N-dimethylacetamide that has been previously dehydrated and dried under stirring, and then samarium metal powder and manganese chloride powder are added in sequence. The molar ratio of samarium powder is 0.5-5 times that of p-nitrobenzyl halide; the molar ratio of paraformaldehyde is 0.5-5 times that of p-nitrobenzyl halide; the molar ratio of manganese chloride is 0.1-1 times that of samarium powder; and the molar ratio of N,N-dimethylacetamide is 5-50 times that of p-nitrobenzyl halide. The reaction system is carried out under anhydrous conditions.

[0012] 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 a chromatographic column to obtain pure p-nitrobenzaldehyde with a yield of 60-70%.

[0013] The advantages and positive effects of the present invention are as follows: the present invention carries out the reaction in the presence of a reducing agent, and p-nitrobenzaldehyde can be synthesized from benzyl chloride without the need for additional addition of an oxidant, thus having unique applicability; the present invention has a simple synthesis route, and p-nitrobenzaldehyde can be obtained 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 oxidants, severe toxicity, light, and biocatalysis are avoided; the raw materials of the present invention are simple and easy to obtain, and the p-nitrobenzyl halide and manganese salt used are low-cost, basic chemical products, and easy to obtain, and the manganese salt is relatively environmentally friendly; the samarium metal 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

[0014] The following synthetic examples are used to further illustrate the present invention but are not intended to limit the present invention.

[0015] Example 1

[0016] Under nitrogen protection, samarium powder (0.3 g, 2 mmol), MnCl2 (0.13 g, 1 mmol), and N,N-dimethylacetamide (5 mL) were mixed, and p-nitrobenzyl bromide (0.43 g, 2 mmol) and paraformaldehyde (0.25 g, 2 mmol) were added with stirring. The temperature was slowly raised to 80°C and the reaction was allowed to proceed 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 p-nitrobenzaldehyde in a yield of 66%.

[0017] White solid; 106-107°C: 1H NMR (500MHz, Chloroform-d) δ10.16 (s, 1H), 8.40 (d, J = 8.6 Hz, 2H), 8.08 (d, J = 8.7 Hz, 2H).

[0018] Example 2

[0019] According to the method of Example 1, using p-nitrobenzyl chloride instead of p-nitrobenzyl bromide, p-nitrobenzaldehyde was obtained with a yield of 52%.

Claims

1. A method for synthesizing p-nitrobenzaldehyde, characterized in that In the presence of manganese chloride, samarium metal is used to promote the one-step reaction of p-nitrobenzyl halide and paraformaldehyde in N,N-dimethylacetamide to prepare p-nitrobenzaldehyde. The preparation process includes the following steps: p-nitrobenzyl halide and paraformaldehyde are uniformly mixed in N,N-dimethylacetamide that has been previously dehydrated and dried under stirring, and then metallic samarium powder and manganese chloride powder are added in sequence. The mixture is stirred at a certain temperature until the reaction is complete, and the resulting reaction mixture is solvent recovered. The residue is post-treated and separated by a chromatographic column to obtain pure p-nitrobenzaldehyde. The amount of samarium powder used is 0.5-5 times the molar ratio of the amount of benzyl halide; the amount of paraformaldehyde used is 0.5-5 times the molar ratio of the amount of p-nitrobenzyl halide; the amount of manganese chloride used is 0.1-1 times the molar ratio of the amount of samarium powder; and the amount of N,N-dimethylacetamide used is 5-50 times the mass of the p-nitrobenzyl halide.

2. A method for synthesizing p-nitrobenzaldehyde according to claim 1, characterized in that The p-nitrobenzyl halide used is selected from one or more of p-nitrobenzyl chloride, p-nitrobenzyl bromide and p-nitrobenzyl iodine.

3. A method for synthesizing p-nitrobenzaldehyde according to claim 1, characterized in that The reaction is a one-pot one-step reaction, the reaction solvent can be recovered, and the reaction yield is 60-70%.

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