CN110981702B - Efficient synthesis method of 2, 3-dibromophenol or derivatives thereof - Google Patents

Abstract

The invention relates to a high-efficiency synthesis method of 2,3-dibromophenol or a derivative thereof. The method comprises the following steps: adding o-dibromobenzene or o-dibromobenzene derivative and tert-butanol peroxy to water, and adding copper The catalyst is then reacted at room temperature for 6-12 hours to obtain 2,3-dibromophenol or 2,3-dibromophenol derivatives through separation and purification. Compared with the prior art, the synthesis process of the invention is simple and green, has excellent selectivity and high yield, and is simple in post-reaction treatment, and uses water as a solvent for environmental protection and safety. The present invention has great application potential in the synthesis of medicines, natural products and the like.

Description

A kind of efficient synthesis method of 2,3-dibromophenol or its derivative

technical field

The invention belongs to the technical field of synthetic chemistry, and relates to an efficient synthesis method of 2,3-dibromophenol or a derivative thereof.

Background technique

Phenolic compounds containing halogen substituents are important intermediates in organic synthesis and pharmaceuticals, and are widely used in the synthesis of fine chemicals such as medicines and pesticides. Among them, 2,3-dibromophenol and its derivatives are important intermediates for the preparation of α-amino acid derivatives and antispasmodic drugs. At present, there are mainly two kinds of synthetic methods of 2,3-dibromophenol: the first method is reported by Sanz et al. to use m-bromophenol as raw material, and obtain the target compound through four-step reaction (J Org Chem, 2005, 70, 6548). ), but in this synthetic route, raw material is expensive, route is longer and yield is lower, is not suitable for suitability for suitability for industrialized production; The second method is that Fujimoto et al. report with ortho-dibromobenzene as raw material, with trifluoroacetic acid and triethyl The target compound can be obtained by amine action (Tetrahedron, 1996, 52, 3889), but this method has poor selectivity for hydroxylation, a large number of by-products are generated, the post-treatment is complicated and the yield is low, and it is not suitable for industrial production. In addition, the indirect method of preparing its boronic acid derivatives through halogenated compounds and then oxidizing them into the corresponding phenolic compounds has also been developed, but the yield of the boronic acid derivatives in the first step is low, and the reaction raw materials More expensive.

With the development of green synthetic chemistry, how to realize the more efficient synthesis of 2,3-dibromophenol and its derivatives has gradually attracted extensive attention, which has very important research significance.

SUMMARY OF THE INVENTION

The purpose of the present invention is to provide a high-efficiency synthesis method of 2,3-dibromophenol or its derivative in order to overcome the defects of the above-mentioned prior art. The method uses water as a solvent, the synthesis process is simple and green, and has excellent selectivity and higher yields.

The object of the present invention can be realized through the following technical solutions:

A kind of efficient synthesis method of 2,3-dibromophenol or its derivative, the method is: adding o-dibromobenzene or o-dibromobenzene derivative, peroxy tert-butanol ( ^tBuOOH ) into water, and adding Copper catalyst, then react at room temperature for 6-12 hours, and then 2,3-dibromophenol or 2,3-dibromophenol derivatives can be obtained through separation and purification.

Further, described ortho-dibromobenzene derivative comprises 4-methyl ortho-dibromobenzene, 4-methoxy ortho-dibromobenzene, 4-nitro ortho-dibromobenzene or 4-dimethylamino ortho-dibromobenzene A type of benzene.

Further, the copper catalyst is copper acetylacetonate (Cu(acac) ₂ ).

Further, the molar ratio of described ortho-dibromobenzene or ortho-dibromobenzene derivative, tert-butanol peroxy, and copper catalyst is 1.0:(1.2-1.5):(0.05-0.10).

Further, 0.4-0.6 mmol of ortho-dibromobenzene or ortho-dibromobenzene derivative is added per 1 mL of water.

As a preferred technical solution, when synthesizing 2,3-dibromophenol, the molar ratio of the o-dibromobenzene, peroxy tert-butanol and copper catalyst is 1.0:1.4:0.10, and 0.5mmol of o-dibromobenzene is added to every 1mL of water. Dibromobenzene, the reaction time was 12 hours.

As a preferred technical solution, when synthesizing 2,3-dibromophenol derivatives, the molar ratio of the ortho-dibromobenzene derivatives, peroxy tert-butanol and copper catalyst is 1.0:1.3:0.10, and every 1 mL of water 0.5 mmol of o-dibromobenzene was added, and the reaction time was 6 hours.

Further, the separation and purification process is as follows: after the reaction is completed, the reaction solution is concentrated and then separated by column chromatography.

In the present invention, under the condition that copper catalyst Cu(acac) ₂ exists, o-dibromobenzene and peroxy tert-butanol ^tBuOOH are added to water, reacted at room temperature for 6-12 hours, and separated and purified to obtain 2,3-dibromophenol or its derivatives. The synthesis process of the invention is simple and green, has excellent selectivity and high yield, and is simple in post-reaction treatment.

Compared with the prior art, the present invention has the following characteristics:

1) The synthesis method of the present invention is simple and green, uses cheap and readily available raw materials and catalysts, has excellent selectivity and high yield, and has great application potential in the synthesis of medicines, natural products and the like.

2) The reaction conditions of the present invention are mild, the post-reaction treatment is simple, and the corresponding product can be obtained in high yield in a one-pot method at room temperature.

3) The present invention uses water as a solvent, which is environmentally friendly and green.

Detailed ways

The present invention will be described in detail below with reference to specific embodiments. This embodiment is implemented on the premise of the technical solution of the present invention, and provides a detailed implementation manner and a specific operation process, but the protection scope of the present invention is not limited to the following embodiments.

Example 1:

In the reaction tube, add o-dibromobenzene (1.0mmol), ^tBuOOH (1.5mmol), Cu(acac) ₂ (0.05mmol) successively, then add solvent water 2mL, react at room temperature for 6 hours, and concentrate the reaction solution after the reaction finishes, The corresponding product was obtained by column chromatography in an isolated yield of 88%. ¹ H NMR (400MHz, CDCl ₃ ): δ 7.21 (dd, J=7.2, 1.5Hz, 1H), 7.11 (t, J=7.5Hz, 1H), 6.97 (dd, J=7.8, 1.5Hz, 1H) ), 5.67(s, 1H). HRMS theoretical value for C ₆ H ₄ Br ₂ O (M) ⁺ : 251.8608, actual measured value: 251.8611.

Example 2:

In the reaction tube, add o-dibromobenzene (1.0mmol), ^tBuOOH (1.2mmol), Cu(acac) ₂ (0.08mmol), then add solvent water 2mL, react at room temperature for 8 hours, and concentrate the reaction solution after the reaction finishes, The corresponding product was obtained by column chromatography in an isolated yield of 90%. ¹ H NMR (400MHz, CDCl ₃ ): δ 7.21 (dd, J=7.2, 1.5Hz, 1H), 7.11 (t, J=7.5Hz, 1H), 6.97 (dd, J=7.8, 1.5Hz, 1H) ), 5.67(s, 1H). HRMS theoretical value for C ₆ H ₄ Br ₂ O (M) ⁺ : 251.8608, actual measured value: 251.8612.

Example 3:

In the reaction tube, add o-dibromobenzene (1.0mmol), ^tBuOOH (1.4mmol), Cu(acac) ₂ (0.10mmol), then add solvent water 2mL, react at room temperature for 12 hours, and concentrate the reaction solution after the reaction ends, The corresponding product was obtained by column chromatography in an isolated yield of 95%. ¹ H NMR (400MHz, CDCl ₃ ): δ 7.21 (dd, J=7.2, 1.5Hz, 1H), 7.11 (t, J=7.5Hz, 1H), 6.97 (dd, J=7.8, 1.5Hz, 1H) ), 5.67(s, 1H). HRMS theoretical value for C ₆ H ₄ Br ₂ O (M) ⁺ : 251.8608, actual measured value: 251.8605.

Example 4:

In the reaction tube, 4-methyl-o-dibromobenzene (1.0mmol), ^tBuOOH (1.5mmol), Cu(acac) ₂ (0.06mmol), and 2mL of solvent water were added successively, and the reaction was carried out at room temperature for 10 hours. After the reaction was completed The reaction solution was concentrated, and the corresponding product was obtained by column chromatography, and the isolated yield was 93%. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.23(s,1H), 7.16(s,1H), 5.72(s,1H), 2.23(s,3H). HRMS theoretical value for _C7H6Br2O (M ⁾⁺ _{: 265.8765} , actual value: 265.8768.

Example 5:

In the reaction tube, add 4-methoxy-o-dibromobenzene (1.0mmol), ^tBuOOH (1.2mmol), Cu(acac) ₂ (0.08mmol), then add solvent water 2mL, and react at room temperature for 8 hours, and the reaction ends Then, the reaction solution was concentrated, and the corresponding product was obtained by column chromatography, and the isolated yield was 91%. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.29 (s, 1H), 7.20 (s, 1H), 5.76 (s, 1H), 3.52 (s, 3H). _HRMS theoretical value for _C7H6Br2O2 (M ⁾⁺ _{: 281.8714} , actual value: 281.8716.

Example 6:

4-Nitro-o-dibromobenzene (1.0mmol), ^tBuOOH (1.3mmol), Cu(acac) ₂ (0.10mmol), 2mL of solvent water were added successively in the reaction tube, and the reaction was carried out at room temperature for 6 hours. The reaction solution was concentrated, and the corresponding product was obtained by column chromatography, and the isolated yield was 96%. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.37 (s, 1H), 7.17 (s, 1H), 5.84 (s, 1H). HRMS theoretical value for _C6H3Br2NO3 ( _M ⁾⁺ _{: 296.8459} , actual value: 296.8463.

Example 7:

4-dimethylamino-o-dibromobenzene (1.0 mmol), ^tBuOOH (1.2 mmol), Cu(acac) ₂ (0.10 mmol), 2 mL of solvent water were added successively to the reaction tube, and the reaction was carried out at room temperature for 12 hours. After the end, the reaction solution was concentrated, and the corresponding product was obtained by column chromatography, and the isolated yield was 93%. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.25 (s, 1H), 7.18 (s, 1H), 5.75 (s, 1H), 2.36 (s, 6H). HRMS theoretical value for _C8H9Br2NO (M ⁾⁺ _{: 294.9030} , actual measured value: 294.9026.

The foregoing description of the embodiments is provided to facilitate understanding and use of the invention by those of ordinary skill in the art. It will be apparent to those skilled in the art that various modifications to these embodiments can be readily made, and the generic principles described herein can be applied to other embodiments without inventive step. Therefore, the present invention is not limited to the above-mentioned embodiments, and improvements and modifications made by those skilled in the art according to the disclosure of the present invention without departing from the scope of the present invention should all fall within the protection scope of the present invention.

Claims (6)

1. a synthetic method of 2,3-dibromophenol or its derivative, is characterized in that, the method is: adding o-dibromobenzene or o-dibromobenzene derivative, tert-butanol peroxy to water, and Add copper catalyst, then react at room temperature for 6-12 hours to obtain 2,3-dibromophenol or 2,3-dibromophenol derivatives after separation and purification; Described ortho-dibromobenzene derivatives include 4-methyl ortho-dibromobenzene, 4-methoxy ortho-dibromobenzene, 4-nitro-ortho-dibromobenzene or 4-dimethylamino ortho-dibromobenzene. A sort of; The copper catalyst is copper acetylacetonate. 2. the synthetic method of a kind of 2,3-dibromophenol or its derivative according to claim 1, is characterized in that, described o-dibromobenzene or o-dibromobenzene derivative, peroxy tert-butanol The molar ratio of the copper catalyst is 1.0:(1.2-1.5):(0.05-0.10). 3. the synthetic method of a kind of 2,3-dibromophenol or its derivative according to claim 2, is characterized in that, every 1mL water adds 0.4-0.6mmol o-dibromobenzene or o-dibromobenzene derivative. 4. the synthetic method of a kind of 2,3-dibromophenol or its derivative according to claim 3, is characterized in that, when synthesizing 2,3-dibromophenol, described o-dibromobenzene, per The molar ratio of oxy-tert-butanol and the copper catalyst was 1.0:1.4:0.10, and 0.5 mmol of o-dibromobenzene was added per 1 mL of water, and the reaction time was 12 hours. 5. the synthetic method of a kind of 2,3-dibromophenol or its derivative according to claim 3, is characterized in that, when synthesizing 2,3-dibromophenol derivative, described o-dibromobenzene The molar ratio of derivative, peroxy tert-butanol and copper catalyst was 1.0:1.3:0.10, 0.5 mmol of o-dibromobenzene derivative was added per 1 mL of water, and the reaction time was 6 hours. 6. the synthetic method of a kind of 2,3-dibromophenol or its derivative according to claim 1, is characterized in that, described separation and purification process is: after reaction finishes, concentrate reaction solution, carry out column chromatography again separation.