A method for synthesizing 9,10-dihydroacridine

Abstract

The present invention discloses a method for synthesizing 9,10-dihydroacridine. This synthesis method uses aniline and o-bromobenzyl alcohol as raw materials, and obtains the final product 9,10-dihydroacridine through a one-pot, two-step reaction. The method of the present invention has the advantages of cheap and easily available raw materials, convenient production, and easy purification, and can be developed into an industrial production method.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for synthesizing 9,10-dihydroacridine. Background Art

[0002] 9,10-Dihydroacridine is a key intermediate frequently used in drug development, chemical industry and optoelectronic materials. However, there are few reports on the synthesis of 9,10-dihydroacridine, and the raw materials are either expensive or the reactions are complicated, which cannot meet the needs of industrial production.

[0003] Therefore, developing a new synthesis method for 9,10-dihydroacridine is of great significance for realizing the industrial production of 9,10-dihydroacridine. Summary of the invention

[0004] The technical problem solved by the invention is to provide a method for synthesizing 9,10-dihydroacridine. The method of the invention has the advantages of cheap and readily available raw materials, convenient production, environmental protection, safety and easy purification.

[0005] In order to solve the above technical problems, the present invention adopts the following technical solution: a synthesis method of 9,10-dihydroacridine, wherein the reaction formula adopted in the synthesis method is:

[0006]

[0007] The synthesis method comprises the steps of:

[0008] (1) In an inert gas environment, in a solvent 1, aniline and o-bromobenzyl alcohol are heated to react in the presence of a catalyst, copper iodide (CuI), and a ligand, L-proline, to prepare an intermediate;

[0009] (2) The intermediate is added with solvent 2 and reacted under the action of aluminum chloride to obtain the final product 9,10-dihydroacridine.

[0010] As an embodiment of the present invention, the molar equivalent ratio of aniline to o-bromobenzyl alcohol, cuprous iodide, L-proline and aluminum chloride is 1:(1-1.5):(0.2-0.5):(0.2-0.5):(1-2).

[0011] Preferably, the molar equivalent ratio of aniline to o-bromobenzyl alcohol, cuprous iodide, L-proline and aluminum chloride is 1:1.2:0.3:0.3:1.3.

[0012] As an embodiment of the present invention, the solvent 1 is selected from any one of dimethyl sulfoxide, N,N-dimethylformamide, and N,N-dimethylacetamide; and the solvent 2 is selected from 1,2-dichloroethane and carbon tetrachloride.

[0013] Preferably, the solvent 1 is dimethyl sulfoxide; and the solvent 2 is carbon tetrachloride.

[0014] As an embodiment of the present invention, in step (1), the reaction temperature is 120-150°C; in step (2), the reaction temperature is 60-90°C.

[0015] Preferably, in step (1), the reaction temperature is 130°C; and in step (2), the reaction temperature is 90°C.

[0016] As an embodiment of the present invention, the inert gas is nitrogen.

[0017] The beneficial effects of the present invention are as follows: the present invention provides a new method for synthesizing 9,10-dihydroacridine, using cheap and readily available aniline and o-bromobenzyl alcohol as raw materials, and obtaining the final product 9,10-dihydroacridine through a one-pot method and two-step reaction. The method of the present invention has the advantages of cheap and readily available raw materials, convenient production, and easy purification, and can be developed into an industrial production method. DETAILED DESCRIPTION

[0018] The technical solution of the present invention is described in detail below through embodiments.

[0019] Example 1

[0020] This embodiment provides a method for synthesizing 9,10-dihydroacridine. Under a nitrogen atmosphere, 0.93 g of aniline is added to a three-necked flask, and then 2.25 g of o-bromobenzyl alcohol is added, followed by 10 ml of dimethyl sulfoxide (DMSO), and then 0.57 g of cuprous iodide and 0.35 g of L-proline are added under nitrogen protection while stirring, and the addition is slowly heated to 130 degrees and reacted for 10 hours. The reaction is monitored by TLC, and the reaction is complete, and then the reaction solution is cooled to room temperature and filtered. The filtrate is diluted with 100 ml of ethyl acetate, then washed with saturated brine, the organic phase is dried, and then spin-dried to obtain a crude intermediate. The crude product does not need to be purified, but is directly dissolved in a carbon tetrachloride solution, and then 1.73 g of aluminum chloride is added in batches under an ice bath, and then heated to 90 degrees and reacted for 8 hours. The reaction is complete under TLC monitoring. Then filter, pour the filtrate into 250 ml of glacial sodium carbonate aqueous solution, separate the liquids, extract the aqueous phase with dichloromethane, combine the organic phases, wash with saturated salt water solution, dry the organic phase, spin dry, and then add it to 10 ml of n-hexane for recrystallization to obtain 1.68 g of product 9,10-dihydroacridine with a yield of 92.8%. The NMR of 9,10-dihydroacridine is:

[0021] 1 H NMR (CDCl 3): δ7.16-7.12(m,4H),6.89(t,J=7.4Hz 2H),6.71(d,J=7.9Hz,2H),5.95(br,1H),4.11(s,2H).

[0022] During the research process, the following experiments were also conducted. The preparation steps were referred to Example 1, and different reagent amounts and solvents were selected, as shown in Table 1 below.

[0023] Table 1

[0024]

[0025] The above descriptions are merely embodiments of the present invention and are not intended to limit the patent scope of the present invention. Any equivalent transformations made using the contents of the present invention specification, or directly or indirectly applied in other related technical fields, are included in the patent protection scope of the present invention.

Claims

1. A method for synthesizing 9,10-dihydroacridine, characterized in that, the reaction formula adopted by the synthesis method is: The synthesis method comprises the steps: (1) Under an inert gas atmosphere, in solvent 1, aniline and o-bromobenzyl alcohol are heated and reacted under the action of a catalyst cuprous iodide and an L-proline ligand to prepare an intermediate; (2) The intermediate is added to solvent 2 and reacted under the action of aluminum trichloride to obtain the final product 9,10-dihydroacridine; The molar equivalent ratio of aniline to o-bromobenzyl alcohol, cuprous iodide, L-proline, and aluminum trichloride = 1:(1 - 1.5):(0.2 - 0.5):(0.2 - 0.5):(1 - 2); The solvent 1 is selected from any one of dimethyl sulfoxide, N,N-dimethylformamide, and N,N-dimethylacetamide; the solvent 2 is selected from 1,2-dichloroethane and carbon tetrachloride.

2. The synthesis method according to claim 1, characterized in that, the molar equivalent ratio of aniline to o-bromobenzyl alcohol, cuprous iodide, L-proline, and aluminum trichloride = 1:1.2:0.3:0.3:1.

3.

3. The synthesis method according to claim 1, characterized in that, the solvent 1 is dimethyl sulfoxide; the solvent 2 is carbon tetrachloride.

4. The synthesis method according to claim 1, characterized in that, in step (1), the reaction temperature is 120 - 150 °C; in step (2), the reaction temperature is 60 - 90 °C.

5. The synthesis method according to claim 4, characterized in that, in step (1), the reaction temperature is 130 °C; in step (2), the reaction temperature is 90 °C.

6. The synthesis method according to claim 1, characterized in that, the inert gas is nitrogen.

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