CN110305016B

CN110305016B - One-step preparation of 4-hydroxybenzyl benzaldehyde carbonate

Info

Publication number: CN110305016B
Application number: CN201910739119.3A
Authority: CN
Inventors: 齐燕; 刘永军
Original assignee: Qingdao University of Science and Technology
Current assignee: Qingdao University of Science and Technology
Priority date: 2019-08-13
Filing date: 2019-08-13
Publication date: 2021-08-31
Anticipated expiration: 2039-08-13
Also published as: CN110305016A

Abstract

The invention discloses a simple method for preparing 4-hydroxybenzyl benzaldehyde carbonate in N, N-dimethylformamide by using halobenzene and carbonic acid diester under the promotion of metal samarium and cuprous iodide. Mixing and dissolving halobenzene and carbonic diester in N, N-dimethylformamide under stirring, and then sequentially adding metal samarium powder and cuprous iodide powder. The reaction system is carried out under anhydrous conditions. Stirring at room temperature until the reaction is complete. The solvent was recovered from the reaction mixture. Separating the crude product by column chromatography to obtain 4-hydroxybenzyl benzaldehyde carbonate, and recrystallizing to obtain pure product with yield of 70-90%.

Description

One-step preparation of 4-hydroxybenzyl benzaldehyde carbonate

Technical Field

The invention belongs to the field of organic chemical synthesis, and particularly relates to a method for synthesizing 4-hydroxybenzyl benzaldehyde carbonate in one step in N, N-dimethylformamide by using cuprous salt as a catalyst from halogenated benzene and carbonic diester.

Background

4-hydroxybenzaldehyde carbonate (I, see the following formula: the same below) is actually 4-hydroxybenzaldehyde (II) protected by carbonate, which is easily converted into 4-hydroxybenzaldehyde as a precursor of 4-hydroxybenzaldehyde by simple hydrolysis, an Organic synthesis and pharmaceutical synthesis intermediate [ document 1.Jeffery Regier, Robert Maillet, Yuri Bolshan, European Journal of Organic Chemistry,2019(13), 2390-; reference 2 Yuri Yamazaki, Makiko Sumikura, Yurika Masuda, et al Bioorganic & Medicinal Chemistry 2012,20(14), 4279-. What is more important, 4-hydroxybenzyl benzoic acid (II-a), 4-hydroxybenzyl benzyl alcohol (II-b), 4-benzoylbenzoic acid (II-c), 4-benzoylbenzyl alcohol (II-d) and 4-benzoylbenzaldehyde (II-e) series of compounds can be prepared very conveniently by using 4-hydroxybenzyl benzaldehyde as a precursor raw material, and these compounds are important intermediates widely used in the field of synthetic chemistry for various purposes [ document 3.Bacani, Genesis M.et al. PCT int.appl., 2018112382,21Jun, 2018; document 4, Harindran Suhana, Muhammad Aliyu Idris, Indian Journal of Chemistry, Section B, Organic Chemistry containing Medicinal Chemistry,2019,58B (3), 416-.

As for the synthesis method of 4-hydroxybenzaldehyde (II), there are mainly addition reaction of Grignard reagent or organolithium reagent with terephthalaldehyde and its monoacetal [ document 5.Regier, Jeffery et al, European Journal of Organic Chemistry,2019(13), 2390-; nagaki, Aiichiro et al Chemistry Letters,2018,47(1),71-73, coupling p-halobenzaldehyde and its analogous compounds with benzaldehyde facilitated by lithium reagents [ document 6.Uemura, Minoru et al, Tetrahedron,2006,62(15), 3523-; document 7.Azzena, Ugo et al tetrahedron,2005,61(13), 3177-. In these methods, there are some problems such as expensive reagents or difficulty in handling air-sensitive reagents, severe reaction conditions, many by-products, low yield, etc.

Samarium is one of rare earth elements. Since the first introduction of samarium diiodide into organic synthesis by the french chemist Kagan in 1980, samarium reagents have been widely used in organic synthesis to promote various types of Chemical reactions and functional group transformations, and have been successfully used in the synthesis of various natural products [ document 9.m.szostak, n.j.fazakerley, d.parmar, d.j.procter, Chemical Reviews,2014, 114,5959-6039 ]. However, samarium diiodide has some disadvantages in use, such as sensitivity to air, difficulty in long-term storage, and generally in-situ preparation at present. On the other hand, samarium diiodide is used as a single electron transfer reagent, and only one electron is utilized in the using process. These limit their use to large scale production. In comparison, samarium is stable in air, easy to operate, relatively cheap, and has more electrons available for effective use. Therefore, the metal samarium is directly used for organic synthesis, and has better prospect. China has abundant rare earth resources, which account for more than 90% of the world reserves, and the development and utilization of the rare earth resources have great significance.

The invention discloses a method for preparing 4-hydroxybenzyl benzaldehyde carbonate (I) by directly promoting one-step reaction of halogenated benzene, carbonate and DMF by using N, N-Dimethylformamide (DMF) as a solvent in the presence of cuprous iodide, wherein the method is not reported in domestic and foreign documents.

Disclosure of Invention

The invention aims to provide a simple method for preparing 4-hydroxybenzyl benzaldehyde carbonate by using halobenzene, DMF and carbonic diester under the promotion of metal samarium and cuprous iodide.

The technical scheme of the invention is as follows:

reducing and coupling halogeno benzene, DMF and carbonic diester into 4-hydroxybenzyl benzaldehyde carbonate at room temperature by using samarium under the existence of cuprous salt, wherein the reaction formula is shown as the following formula:

in the formula, X is preferably Br, I; r is preferably CH₃，C₂H₅。

The technical scheme of the invention is as follows: mixing and dissolving halogenated benzene and carbonic diester in N, N-dimethylformamide dehydrated and dried in advance under stirring, and then sequentially adding metal samarium powder and cuprous iodide powder. Wherein the use amount of the carbonic diester is 0.5 to 5 times of the mole ratio of the use amount of the halogenated benzene; the dosage of the samarium powder is 0.5 to 5 times of the molar ratio of the dosage of the carbonic diester; the dosage of cuprous iodide is 0.5-5 times of the molar ratio of the dosage of samarium powder; the dosage of the N, N-dimethylformamide is 10-100 times of the mass of the carbonic diester; the reaction system is carried out under anhydrous conditions.

Stirring at room temperature until the reaction is complete. Recovering solvent from the obtained reaction mixture, post-treating the residue, and separating with chromatographic column to obtain 4-hydroxybenzyl benzaldehyde carbonate with yield of 60-90%.

The invention has the advantages and positive effects that: the synthetic route is simple and efficient, the 4-hydroxybenzyl benzaldehyde carbonate can be obtained by one-step reaction, the operation steps are few, an intermediate is not required to be separated, and the operation requirement is greatly simplified; the reaction condition of the invention is easy to realize, and the invention can be directly operated in the air, thereby avoiding the special requirements of no oxygen, low temperature, high temperature, illumination, biological catalysis and the like; the product obtained by the invention is the 4-hydroxybenzyl benzaldehyde protected by the carbonic ester, and the step of protecting in advance can be avoided when further carrying out oxidation reaction and the like to prepare other derivative products; the raw materials are simple and easy to obtain, and the carbonic diester and the halogenated benzene are basic chemical products and are easy to obtain; the metal samarium used in the invention is rare earth metal, and the rare earth resource in China accounts for more than 90 percent of the world, so the effective development and utilization of the rare earth metal have great significance to China; the 4-hydroxybenzyl benzaldehyde carbonate synthesized by the method has high yield, simple post-treatment process and easy separation during the post-treatment of the product; the solvent N, N-dimethylformamide used in the invention can be fully recycled, and thus the reaction cost is further reduced.

Detailed Description

The following synthetic examples serve to further illustrate the invention, but are not meant to limit the invention.

Example 1

0.3g of freshly prepared samarium powder and 0.04g of cuprous iodide were sequentially added to the reaction vessel, followed by 10mL of N, N-dimethylformamide previously dehydrated and dried, and magnetically stirred. 0.2mL of bromobenzene and 3mL of dimethyl carbonate were added. The reaction solution darkens within 2h and continues to react for 8 h. 5mL of dilute hydrochloric acid (2 mol. L) was added^-1) The reaction was terminated, and the reaction mixture was worked up to give a crude product, which was then further purified by a column chromatography to give 4-hydroxybenzyl benzaldehyde methyl carbonate in 83% yield.

White solid, m.p.87-89 ℃,¹H NMR(500MHz,CDCl₃)δ10.00(s,1H),7.87(d,J ＝8.0Hz,2H),7.55(d,J＝8.0Hz,2H),7.36(m,J＝4.1Hz,5H),6.73(s,1H),3.81(s, 3H).¹³C NMR(125MHz,CDCl₃)δ191.74(s),155.01(s),146.22(s),138.73(s), 136.03(s),130.05(s),128.75(d,J＝20.8Hz),127.25(d,J＝15.3Hz),80.21(s), 55.14(s).

example 2

Using iodobenzene instead of bromobenzene, 4-hydroxybenzyl benzaldehyde methyl carbonate was obtained in 81% yield as in example 1.

Example 3

Using diethyl carbonate instead of dimethyl carbonate, 4-hydroxybenzaldehyde ethyl carbonate was obtained in 72% yield according to the procedure of example 1.

Claims

1. A simple method for synthesizing 4-hydroxybenzyl benzaldehyde carbonate is characterized in that in the presence of cuprous iodide, samarium is used for promoting halobenzene and carbonic diester to react in one step in N, N-dimethylformamide to prepare the 4-hydroxybenzyl benzaldehyde carbonate, and the preparation process comprises the following steps:

mixing and dissolving halobenzene and carbonic diester in N, N-dimethylformamide dehydrated and dried in advance under the stirring at room temperature, then sequentially adding metal samarium powder and cuprous iodide powder, stirring at room temperature until the reaction is complete, recovering the solvent from the obtained reaction mixed solution, and after carrying out post-treatment on the residue, carrying out chromatographic column separation to obtain a pure 4-hydroxybenzyl benzaldehyde carbonate product.

2. The simplified process for the synthesis of 4-hydroxybenzaldehyde carbonates according to claim 1, characterized in that the carbonic acid diester used is in a molar ratio of 0.5 to 5 times the amount of halogenobenzene; the dosage of samarium powder is 0.5 to 5 times of the molar ratio of the dosage of halobenzene; the dosage of cuprous iodide is 0.5-5 times of the molar ratio of the dosage of samarium powder; the dosage of the N, N-dimethylformamide is 10-100 times of the mass of the halobenzene.

3. The simplified process for synthesizing 4-hydroxybenzaldehyde carbonate according to claim 1, wherein the carbonic acid diester used is one or more of dimethyl carbonate and diethyl carbonate.

4. The method as claimed in claim 1, wherein the halobenzene is one or more of chlorobenzene, bromobenzene and iodobenzene.

5. The simple process for synthesizing 4-hydroxybenzyl benzaldehyde carbonate according to claim 1, wherein the reaction process is a one-pot one-step reaction, the reaction temperature is room temperature, the reaction solvent can be recovered, and the reaction yield is 60-90%.