CN112500346B

CN112500346B - Synthesis method of 5, 6-dihydrobenzo [ c ] acridine

Info

Publication number: CN112500346B
Application number: CN202011524108.2A
Authority: CN
Inventors: 谢艳军; 王晶晶; 阳海; 易兵
Original assignee: Hunan Institute of Engineering
Current assignee: Hunan Institute of Engineering
Priority date: 2020-12-12
Filing date: 2020-12-12
Publication date: 2022-03-01
Anticipated expiration: 2040-12-12
Also published as: CN112500346A

Abstract

The invention relates to a synthetic method of 5, 6-dihydrobenzo [ c ] acridine. The invention converts 1-tetralone oxime ester and o-fluorine or o-chlorobenzaldehyde into 5, 6-dihydrobenzo [ c ] acridine under the catalysis of copper and in air atmosphere, and the prepared product has stable structure and excellent chemical property. The reaction raw materials of the synthesis method are cheap and easy to obtain, and do not need to be pretreated, and the atom economy of the reaction is high; the reaction only needs to use a cheap copper catalyst, so that raw materials are saved, and the reaction cost is reduced; the whole reaction system is simple, the reaction condition is mild, reaction equipment is less, the experimental operation is simple and convenient, and the material source is wide.

Description

Synthesis method of 5, 6-dihydrobenzo [ c ] acridine

Technical Field

The invention relates to a method for synthesizing 5, 6-dihydrobenzo [ c ] acridine, belonging to the technical field of organic compound synthesis.

Background

Acridine is an important nitrogen-containing aromatic heterocyclic compound, and a nitrogen heterocyclic compound is indispensable for clinically important medicaments, is widely applied to organic synthesis, and has extremely high application value in the fields of medicines, materials and the like.

Disclosure of Invention

Therefore, the invention aims to provide a method for synthesizing 5, 6-dihydrobenzo [ c ] acridine, which has the advantages of simple reaction conditions and convenient operation.

The invention provides 5, 6-dihydrobenzo [ c ] acridine compounds, the structural formula of which is formula I:

the invention also provides a synthesis method for synthesizing 5, 6-dihydrobenzo [ c ] acridine, which is obtained by heating and stirring 1-tetralone oxime ester and o-halobenzaldehyde in a pot under the combined action of an additive, a catalyst, a ligand and an organic solvent for reaction.

Further, the additive is one of sodium bisulfite, sodium thiosulfate, sodium dithionate and potassium bisulfite, and sodium bisulfite is preferred.

Further, the catalyst is one of cuprous chloride, cuprous bromide, cuprous iodide, cupric chloride, cupric bromide and cupric acetate, and is preferably cuprous chloride.

Further, the ligand is one of 2, 2 '-bipyridine, 2' -biquinoline, 1, 10-phenanthroline, 2, 9-dimethyl-1, 10-phenanthroline and 2, 9-di-tert-butyl-1, 10-phenanthroline, and 1, 10-phenanthroline is preferred.

Further, the solvent is one of 1, 2-dichloroethane, 1, 2, 2-tetrachloroethane, chlorobenzene, toluene, N-dimethylformamide and dimethyl sulfoxide, and 1, 2-dichloroethane is preferred.

Furthermore, the mol ratio of the o-fluorobenzaldehyde to the 1-tetralone oxime ester to the additive to the catalyst to the ligand is 1: 1-1.5: 0.1-0.2: 0.5-2, wherein the preferable ratio is 1: 1.5: 0.15: 1.

Further, the reaction temperature is 120-160 ℃, preferably 130 ℃.

Further, the 1-tetralone oxime ester has a structural formula II:

further, the structure formula of the o-halobenzaldehyde is III:

the technical scheme of the invention has the following advantages:

the invention converts 1-tetralone oxime ester compounds and o-fluorine or o-chlorobenzaldehyde into 5, 6-dihydrobenzo [ c ] acridine under the catalysis of copper catalysts in the air atmosphere, and the prepared product has stable structure; the reaction raw materials are cheap and easy to obtain, the process is scientific and reasonable, the operation is easy, the reaction steps are few, and the required equipment is few; the method has the characteristics of simple reaction system, mild reaction conditions, high product utilization value, expected market commercialization prospect and the like.

Drawings

To demonstrate the products of the invention, the invention provides the nuclear magnetic hydrogen and carbon spectra of example 1.

FIG. 1 is a nuclear magnetic hydrogen spectrum of the product of example 1.

FIG. 2 is a nuclear magnetic carbon spectrum of the product of example 1.

FIG. 3 is a reaction equation of the synthesis reaction of the present invention.

Detailed Description

The present invention will now be described in further detail with reference to the accompanying drawings.

The reaction equation is:

example 1

A method for synthesizing 5, 6-dihydrobenzo [ c ] acridine comprises the following steps:

the method comprises the following steps:

step 1: adding 1-tetralone oxime ester, o-fluorobenzaldehyde, an additive, a ligand, a catalyst and an organic solvent into a reaction vessel;

step 2: heating the reaction vessel by using an oil bath pan;

and step 3: and after the reaction is finished, performing column chromatography purification to obtain a product.

Table 1: the molar ratios of o-halobenzaldehyde, 1-tetralone oxime ester, catalyst, ligand and additive, reaction temperature and reaction time in examples 1 to 10

Is the mol ratio of o-fluorobenzaldehyde, ketoxime ester compounds, catalyst, ligand and additive

The conversion rate of the substance in the reaction vessel after the step 3 was measured and nuclear magnetic resonance was performed, and the results of the example were as follows:

the nuclear magnetic data for the products of examples 1-10 are as follows:

¹H NMR(400MHz，CDCl₃)δ8.56(dd，J＝7.7，1.5Hz，1H)，8.13(d，J＝8.5Hz，1H)，7.84(s，1H)，7.68 (dd，J＝8.1，1.4Hz，1H)，7.61(ddd，J＝8.4，6.8，1.5Hz，1H)，7.46-7.37(m，2H)，7.34(td，J＝7.4，1.5Hz， 1H)，7.25-7.20(m，1H)，3.05(dd，J＝8.5，5.3Hz，2H)，2.95(dd，J＝8.4，5.3Hz，2H)；¹³C NMR(100MHz， CDCl₃)δ153.3，147.4，139.4，134.5，133.7，130.5，129.6，129.2，128.6，127.9，127.7，127.2，126.9，126.0， 28.7，28.3.

TABLE 2 yield and product structure of the reactions of examples 1-10

In light of the foregoing description of the preferred embodiment of the present invention, many modifications and variations will be apparent to those skilled in the art without departing from the spirit and scope of the invention. The technical scope of the present invention is not limited to the content of the specification, and must be determined according to the scope of the claims.

Claims

1. A synthetic method for synthesizing 5, 6-dihydrobenzo [ c ] acridine is characterized in that 1-tetralone oxime ester and o-halobenzaldehyde are heated and stirred to react under the combined action of an additive, a catalyst, a ligand and an organic solvent to obtain the compound under the reaction condition;

a 5, 6-dihydrobenzo [ c ] acridine compound having the structural formula I:

the structural formula of the 1-tetralone oxime ester is II:

the structural formula of the o-halobenzaldehyde is III:

wherein

The ligand is one of 2, 2 '-bipyridyl, 2' -biquinoline, 1, 10-phenanthroline, 2, 9-dimethyl-1, 10-phenanthroline and 2, 9-di-tert-butyl-1, 10-phenanthroline.

2. The method of claim 1, wherein the catalyst is one of cuprous chloride, cuprous bromide, cuprous iodide, cupric chloride, cupric bromide, and cupric acetate.

3. The method of claim 1, wherein the additive is one of sodium bisulfite, sodium thiosulfate, sodium dithionate, potassium bisulfite.

4. The method of claim 1, wherein the solvent is one of 1, 2-dichloroethane, 1, 2, 2-tetrachloroethane, chlorobenzene, toluene, N-dimethylformamide, and dimethylsulfoxide.

5. The method of claim 1, wherein the molar ratio of the o-halobenzaldehyde, the 1-tetralone oxime ester, the catalyst, the ligand and the additive is 1: 1 to 1.5: 0.1 to 0.2: 0.5 to 2.

6. The method according to claim 1, wherein the reaction temperature is 120 to 160 ℃.