CN117105790A - Method for preparing p-nitrobenzaldehyde from p-nitrobenzyl halide - Google Patents
Method for preparing p-nitrobenzaldehyde from p-nitrobenzyl halide Download PDFInfo
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- CN117105790A CN117105790A CN202311047606.6A CN202311047606A CN117105790A CN 117105790 A CN117105790 A CN 117105790A CN 202311047606 A CN202311047606 A CN 202311047606A CN 117105790 A CN117105790 A CN 117105790A
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- nitrobenzaldehyde
- nitrobenzyl
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- halide
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- BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 title claims abstract description 24
- -1 p-nitrobenzyl halide Chemical class 0.000 title claims abstract description 22
- 238000000034 method Methods 0.000 title claims abstract description 13
- KZUNJOHGWZRPMI-UHFFFAOYSA-N samarium atom Chemical compound [Sm] KZUNJOHGWZRPMI-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 16
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229910052751 metal Inorganic materials 0.000 claims abstract description 11
- 239000002184 metal Substances 0.000 claims abstract description 11
- 229930040373 Paraformaldehyde Natural products 0.000 claims abstract description 10
- 229910052772 Samarium Inorganic materials 0.000 claims abstract description 10
- 229920002866 paraformaldehyde Polymers 0.000 claims abstract description 10
- 229910021380 Manganese Chloride Inorganic materials 0.000 claims abstract description 9
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 claims abstract description 9
- 229940099607 manganese chloride Drugs 0.000 claims abstract description 9
- 235000002867 manganese chloride Nutrition 0.000 claims abstract description 9
- 239000011565 manganese chloride Substances 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims abstract description 7
- 239000000843 powder Substances 0.000 claims abstract description 3
- 238000005580 one pot reaction Methods 0.000 claims description 5
- 230000002194 synthesizing effect Effects 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 4
- VOLRSQPSJGXRNJ-UHFFFAOYSA-N 4-nitrobenzyl bromide Chemical compound [O-][N+](=O)C1=CC=C(CBr)C=C1 VOLRSQPSJGXRNJ-UHFFFAOYSA-N 0.000 claims description 3
- KGCNHWXDPDPSBV-UHFFFAOYSA-N p-nitrobenzyl chloride Chemical compound [O-][N+](=O)C1=CC=C(CCl)C=C1 KGCNHWXDPDPSBV-UHFFFAOYSA-N 0.000 claims description 2
- 230000001737 promoting effect Effects 0.000 claims description 2
- INKNHBKFSPIMKS-UHFFFAOYSA-N 1-(iodomethyl)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(CI)C=C1 INKNHBKFSPIMKS-UHFFFAOYSA-N 0.000 claims 1
- 239000007810 chemical reaction solvent Substances 0.000 claims 1
- 239000011259 mixed solution Substances 0.000 claims 1
- 239000011541 reaction mixture Substances 0.000 abstract description 3
- 239000012043 crude product Substances 0.000 abstract description 2
- 238000011084 recovery Methods 0.000 abstract description 2
- 238000004440 column chromatography Methods 0.000 abstract 1
- 238000001953 recrystallisation Methods 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 229910052761 rare earth metal Inorganic materials 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 150000002910 rare earth metals Chemical class 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 4
- UAWABSHMGXMCRK-UHFFFAOYSA-L samarium(ii) iodide Chemical compound I[Sm]I UAWABSHMGXMCRK-UHFFFAOYSA-L 0.000 description 4
- 150000002696 manganese Chemical class 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000006578 reductive coupling reaction Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- ZPTVNYMJQHSSEA-UHFFFAOYSA-N 4-nitrotoluene Chemical compound CC1=CC=C([N+]([O-])=O)C=C1 ZPTVNYMJQHSSEA-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000012824 chemical production Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-O morpholinium Chemical class [H+].C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-O 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000027756 respiratory electron transport chain Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/10—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of rare earths
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/06—Halogens; Compounds thereof
- B01J27/08—Halides
- B01J27/10—Chlorides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a simple method for preparing p-nitrobenzaldehyde by using p-nitrobenzyl halide and paraformaldehyde in N, N-dimethylacetamide under the promotion of metal samarium and manganese chloride. Adding p-nitrobenzyl halide and paraformaldehyde into N, N-dimethylacetamide under stirring, and then sequentially adding metal samarium powder and manganese chloride powder. The reaction system is carried out under anhydrous conditions. Stirring at 80 ℃ until the reaction is complete. The obtained reaction mixture was subjected to solvent recovery. The crude product is separated by column chromatography and distilled to remove the solvent for recrystallization to obtain the p-nitrobenzaldehyde with the yield of 60-70 percent.
Description
Technical Field
The invention belongs to the field of organic chemical synthesis, and in particular relates to a method for synthesizing p-nitrobenzaldehyde in N, N-dimethylacetamide by using a reducing reagent, namely metal samarium to promote lower manganese salt to catalyze p-nitrobenzyl halide and paraformaldehyde in one step.
Background
P-nitrobenzaldehyde is an important intermediate for organic synthesis and preparation of fine chemicals such as medicines, dyes, pesticides, etc., and plays a very important role in the synthesis of medicines in particular [ document 1. Ji Lei (2008) & p-nitrobenzaldehyde synthesis process research (Doctoral dissertation) & Nanjing university ]. In the doctor's theory cited above, the practical application of p-nitrobenzaldehyde is listed, and the conventional synthesis method of the compound is described in detail, including p-nitrotoluene oxidation, benzyl chloride nitration, hydrolysis, oxidation, etc., and specific reference is made thereto. The synthetic methods have different raw materials, different methods, different applicable conditions and environments of reaction routes, and are widely applied to the fields of chemical production, organic synthesis and the like.
The preparation of p-nitrobenzaldehyde is generally not possible by the reduction of organometallic reagents or carboxylic acid derivatives due to the effect of the nitro group on the benzene ring. From p-nitrobenzyl halides, p-nitrobenzaldehyde can be produced by oxidation, for example with substituted morpholinium oxynitrides [ document 2.Tabata, masayuki; european Journal of Organic Chemistry (2014), 2014 (16), 3402-3410 ], and hydrogen peroxide under certain conditions to perform an oxidation reaction [ document 3.Russell, glen A.; journal of Organic Chemistry (1979), 44 (22), 3990-3991]. The reaction conditions of these processes must be carried out in the presence of oxidizing agents, which cannot be used due to the presence of nitro groups when reducing conditions or reagents are present in the synthetic route. Under the reducing conditions of reducing agents and the like, the synthesis of p-nitrobenzaldehyde by using p-nitrobenzyl halide is rarely realized in literature at present.
Samarium is one of rare earth elements. Samarium diiodide has been very widely used in organic synthesis since its first introduction into organic synthesis by Kagan, a french chemist, 1980 as a reductive coupling reagent which promotes various types of chemical reactions and functional group conversions, and has been successfully applied to the synthesis of various natural products [ document 4. Szostank, m.; fazakerley, n.j.; parmar, d.; et al, chemical Reviews (2014), 114,5959-6039]. However, samarium diiodide has some disadvantages in use, such as being very sensitive to air, so that long-term storage is difficult, and the samarium diiodide is generally prepared on the spot. On the other hand, samarium diiodide is used as a single electron transfer reagent, and only one electron is utilized during use. These limit their use in large scale preparations. In contrast, the samarium metal is stable in air, easy to operate, relatively inexpensive, and more electrons can be effectively utilized. Therefore, the direct application of the samarium metal to organic synthesis has better prospect. The rare earth resources are abundant in China, account for more than 90% of world reserves, and the development and utilization of the rare earth resources have great significance.
The invention discloses a method for preparing a p-nitrobenzaldehyde compound by directly promoting one-step reaction of p-nitrobenzyl halide and paraformaldehyde by using a reducing reagent, namely samarium, in the presence of manganese chloride by taking N, N-Dimethylacetamide (DMA) as a solvent.
Disclosure of Invention
The invention aims to provide a simple method for preparing p-nitrobenzaldehyde by using p-nitrobenzyl halide and N, N-dimethylacetamide as a solvent under the promotion of metal samarium and manganese chloride.
The technical scheme of the invention is as follows:
in the presence of manganese salt, the p-nitrobenzyl halide and DMA are subjected to reductive coupling to p-nitrobenzaldehyde under mild conditions by using samarium metal, and the reaction general formula is shown as follows:
wherein X=Cl, br, I
The technical scheme of the invention is as follows: adding p-nitrobenzyl halide and paraformaldehyde into N, N-dimethylacetamide which is dehydrated and dried in advance under stirring, and then sequentially adding metal samarium powder and manganese chloride powder. Wherein the dosage of samarium powder is 0.5-5 times of the molar ratio of the dosage of the p-nitrobenzyl halide; the dosage of paraformaldehyde is 0.5-5 times of the molar ratio of the dosage of the p-nitrobenzyl halide; the manganese chloride dosage is 0.1-1 times of the samarium powder dosage in terms of molar ratio; the dosage of the N, N-dimethylacetamide is 5-50 times of the mass of the p-nitrobenzyl halide; the reaction system is carried out under anhydrous conditions.
Slowly heating to 80 ℃ and stirring until the reaction is complete. The obtained reaction mixture is subjected to solvent recovery, and after the residue is subjected to post-treatment, the pure p-nitrobenzaldehyde is obtained through chromatographic column separation, and the yield is 60-70%.
The invention has the advantages and positive effects that: the invention reacts in the presence of the reducing agent, and the p-nitrobenzaldehyde can be synthesized from benzyl chloride without adding an oxidant, so that the invention has unique applicability; the invention has simple synthetic route, can obtain the p-nitrobenzaldehyde by one-step reaction, has few operation steps, does not need to separate intermediates, and greatly simplifies the operation requirement; the reaction condition of the invention is easy to realize, and the special requirements of strong oxidant, severe toxicity, illumination, biocatalysis and the like are avoided; the raw materials of the invention are simple and easy to obtain, the used p-nitrobenzyl halide and manganese salt have low cost, are all basic chemical products, are easy to obtain, and are relatively friendly to the environment; the samarium metal is rare earth metal, and the rare earth resource of China occupies the first place of the world, so that the effective development and utilization of the rare earth metal has great significance to China; the solvent N, N-dimethylacetamide used in the invention can be fully recovered and reused, and thus the reaction cost is further reduced.
Detailed Description
The following synthesis examples serve to further illustrate the invention but are not meant to limit it.
Example 1
Samarium powder (0.3 g,2 mmol) and MnCl are added under the protection of nitrogen 2 (0.13 g,1 mmol) and N, N-dimethylacetamide (5 mL) were mixed and para-nitrobenzyl bromide (0.43 g,2 mmol) was added with stirring, paraformaldehyde (0.25 g,2 mmol). Slowly heating to 80 ℃ for reaction for 4 hours. Quenching with dilute hydrochloric acid (1 mol. L) -1 10 mL). The reaction mixture was post-treated to give a crude product, which was further purified by chromatography to give p-nitrobenzaldehyde in 66% yield.
White solid; 106-107℃: 1 H NMR(500MHz,Chloroform-d)δ10.16(s,1H),8.40(d,J＝8.6Hz,2H),8.08(d,J＝8.7Hz,2H).
example 2
The p-nitrobenzaldehyde was obtained in 52% yield as in example 1 using p-nitrobenzyl chloride instead of p-nitrobenzyl bromide.
Claims (4)
1. A simple method for synthesizing p-nitrobenzaldehyde is characterized in that in the presence of manganese chloride, metal samarium is used for promoting one-step reaction of p-nitrobenzyl halide and paraformaldehyde in N, N-dimethylacetamide to prepare the p-nitrobenzaldehyde, and the preparation process comprises the following steps:
the p-nitrobenzyl halide and the paraformaldehyde are uniformly mixed in N, N-dimethylacetamide which is dehydrated and dried in advance under stirring, and then the metal samarium powder and the manganese chloride powder are sequentially added. Stirring at a certain temperature until the reaction is complete. And (3) recovering the solvent of the obtained reaction mixed solution, and separating the residue by a chromatographic column after post-treatment to obtain the pure p-nitrobenzaldehyde.
2. The simple method for synthesizing p-nitrobenzaldehyde according to claim 1, wherein the dosage of samarium powder is 0.5-5 times of the molar ratio of benzyl halide; the dosage of paraformaldehyde is 0.5-5 times of the molar ratio of the dosage of the p-nitrobenzyl halide; the manganese chloride dosage is 0.1-1 times of the samarium powder dosage in terms of molar ratio; the dosage of the N, N-dimethylacetamide is 5-50 times of the mass of the p-nitrobenzyl halide.
3. The simple process for synthesizing p-nitrobenzaldehyde according to claim 1, wherein the p-nitrobenzyl halide is one or more of p-nitrobenzyl chloride, p-nitrobenzyl bromide and p-nitrobenzyl iodide.
4. The simple method for synthesizing p-nitrobenzaldehyde according to claim 1, wherein the reaction is a one-pot one-step reaction, the reaction solvent can be recovered, and the reaction yield is 60-70%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311047606.6A CN117105790A (en) | 2023-08-19 | 2023-08-19 | Method for preparing p-nitrobenzaldehyde from p-nitrobenzyl halide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311047606.6A CN117105790A (en) | 2023-08-19 | 2023-08-19 | Method for preparing p-nitrobenzaldehyde from p-nitrobenzyl halide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117105790A true CN117105790A (en) | 2023-11-24 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311047606.6A Pending CN117105790A (en) | 2023-08-19 | 2023-08-19 | Method for preparing p-nitrobenzaldehyde from p-nitrobenzyl halide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117105790A (en) |
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2023
- 2023-08-19 CN CN202311047606.6A patent/CN117105790A/en active Pending
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