Preparation method of intermediate 1, 3, 5-tribromobenzene of 1, 3, 5-trimethoxybenzene

Abstract

The invention relates to a preparation method of 1, 3, 5-tribromobenzene as an intermediate of 1, 3, 5-trimethoxybenzene, which is characterized by comprising the following steps: mixing 2, 4, 6-tribromoaniline (TBA) with a diazotization reagent in a proper solvent to react for 8-48 hours at 20-65 DEG C, and purifying to obtain 1, 3, 5-tribromobenzene (TBB); the diazotization reagent is sodium nitrite; the solvent is one or more of methanol, toluene, ethanol and isopropanol. The method has the advantages that the use amount of a solvent in a synthesis process is changed for the first time, the 1, 3, 5-trimethoxybenzene intermediate TBB is synthesized, 2, 4, 6-tribromoaniline is used as a raw material, and the intermediate TBB is obtained by removing amino through the action of a diazotization reagent; the method is reasonable, simple, easy to operate and high in yield, and the purity meets the quality research requirement.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical synthesis, and particularly relates to a method for preparing 1,3,5-tribromobenzene, an intermediate of 1,3,5-trimethoxybenzene. Background Art

[0002] 1,3,5-Trimethoxybenzene (TMB) is a white crystalline powder, insoluble in water, and an important organic synthesis intermediate. It is mainly used in the fields of pharmaceutical manufacturing and pesticide synthesis. It is an important raw material for the synthesis of buflomedil, a new dilation drug for peripheral vascular disorders. The structural formula of 1,3,5-trimethoxybenzene is shown below: .

[0003] At present, how to simply and effectively prepare 1,3,5-tribromobenzene (TBB), an intermediate of 1,3,5-trimethoxybenzene, is a research topic. Summary of the invention

[0004] In order to solve the above technical problems, the present invention proposes a method for preparing 1,3,5-tribromobenzene, an intermediate of 1,3,5-trimethoxybenzene, which has an ingenious design, a reasonable and perfect process, and optimizes the synthesis method of TBB, an intermediate of 1,3,5-trimethoxybenzene (TMB).

[0005] The technical solution of the present invention: A method for preparing 1,3,5-tribromobenzene, an intermediate of 1,3,5-trimethoxybenzene, characterized in that 2,4,6-tribromoaniline (TBA) is mixed with a diazotizing agent in a suitable solvent for reaction, reacted at 20-65° C. for 8-48 hours, and purified to obtain 1,3,5-tribromobenzene (TBB); ; The diazotizing agent is sodium nitrite; the solvent is one or more of methanol, toluene, ethanol and isopropanol.

[0006] The reaction temperature is 20°C to 65°C; the reaction time is 8 hours to 48 hours.

[0007] The solvent is preferably methanol.

[0008] The reaction temperature is preferably 55-57°C.

[0009] The reaction time is preferably 10 hours.

[0010] The invention has the advantages that the amount of solvent used in the synthesis process is changed for the first time, and the 1,3,5-trimethoxybenzene intermediate TBB is synthesized. 2,4,6-tribromoaniline is used as a raw material, and the amino group is removed through the action of a diazotization reagent to obtain the intermediate TBB. The method is reasonable, simple, easy to operate, high in yield, and the purity meets the quality research requirements. DETAILED DESCRIPTION

[0011] All features disclosed in this specification, or all steps in the methods or processes disclosed, except for mutually exclusive features and / or steps, can be combined in any way. Example

[0012] Synthesis of 1,3,5-tribromobenzene (TBB): .

[0013] Take 70g methanol, add 26.1g TBA (total weight 87%), 0.12g anhydrous copper sulfate, and finally add the remaining 3.9g TBA (total weight 13%) (the order of feeding cannot be changed). Slowly add 9.78g concentrated sulfuric acid at room temperature, and keep warm for 1h. Heat to 55℃, add 6.66g sodium nitrite in batches, and take 5h. Keep warm for 3h. Distill 13.5g fraction at normal pressure. Add 21.6g water, and distill more than 31.5g fraction at normal pressure. Add 21.6g water, slowly cool to 20~30℃, and filter. Add 38.7g water to the filter cake, beat at room temperature for 1h, and filter. Add 22.86g methanol to the filter cake, beat at 30℃ for 2h, cool to 20℃, beat for 1h, and filter. After drying, 27 g of the product was obtained with a yield of 94.4% and a purity of 99.62% (HPLC, calculated by area normalization method). Example

[0014] Take 100g methanol, add 26.1g TBA (total weight 87%), 0.12g anhydrous copper sulfate, and finally add the remaining 3.9g TBA (total weight 13%) (the order of feeding cannot be changed). Slowly add 9.78g concentrated sulfuric acid at room temperature, and keep warm for 1h. Heat to 55℃, add 6.66g sodium nitrite in batches, and take 5h. Keep warm for 3h. Distill 13.5g fraction at normal pressure. Add 21.6g water, and distill more than 31.5g fraction at normal pressure. Add 21.6g water, slowly cool to 20~30℃, and filter. Add 38.7g water to the filter cake, beat at room temperature for 1h, and filter. Add 22.86g methanol to the filter cake, beat at 30℃ for 2h, cool to 20℃, beat for 1h, and filter. After drying, 27 g of the product was obtained with a yield of 94.4% and a purity of 99.62% (HPLC, calculated by area normalization method).

Claims

1. A method for preparing 1,3,5-tribromobenzene, an intermediate of 1,3,5-trimethoxybenzene, characterized in that: 2,4,6-tribromoaniline (TBA) is mixed with a diazotizing agent in a suitable solvent for reaction at 20-65°C for 8-48 hours, and 1,3,5-tribromobenzene (TBB) is obtained after purification; ； The diazotizing agent is sodium nitrite; the solvent is one or more of methanol, toluene, ethanol and isopropanol.

2. The method for preparing 1,3,5-tribromobenzene, an intermediate of 1,3,5-trimethoxybenzene according to claim 1, characterized in that: The reaction temperature is 20°C to 65°C; the reaction time is 8 hours to 48 hours.

3. The method for preparing 1,3,5-tribromobenzene, an intermediate of 1,3,5-trimethoxybenzene according to claim 1, characterized in that: The solvent is methanol.

4. The method for preparing 1,3,5-tribromobenzene, an intermediate of 1,3,5-trimethoxybenzene according to claim 1, characterized in that: The reaction temperature is 55-57°C.

5. The method for preparing 1,3,5-tribromobenzene, an intermediate of 1,3,5-trimethoxybenzene according to claim 1, characterized in that: The reaction time required is 10 hours.

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