High-regioselectivity bromination method for phenol compounds

A phenolic compound, high-regional technology, applied in the field of high-regional selective bromination of phenolic compounds, can solve the problems of inconvenient recovery, unsatisfactory reaction yield, low selectivity, etc., to reduce the cost of separation and purification, and the raw material is suitable The effect of wide range and simple reaction system

Active Publication Date: 2019-05-17
XINYANG NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Brominated phenol can undergo Heck reaction, Suzuki coupling reaction, Ullmann coupling reaction, etc., and can be further converted into structural units with more complex and diverse structures. However, the bromination reaction of phenol still has low regioselectivity and unsatisfactory reaction yields. However, there is still an urgent need to develop a highly regioselective phenol bromination reaction method, etc.
[0003] The synthesis methods reported in the literature mainly include: (1) The electrophilic substitution reaction of aromatic rings between phenol and bromine electrophiles (such as: liquid bromine, nitrogen-bromobutadiene amine imine, etc.) occurs, but usually 2-bromine Phenol, a mixture of 4-bromophenol and 2,-4-dibromophenol, low selectivity, difficult separation and purification ( Org. Biomol. Chem., 2003, 1, 2506; Tetrahedron ,2010, 66,6928; J. Org. Chem. , 2018, 83, 930); (2) phenol reacts with bromide (such as potassium bromid

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Embodiment 1 phenol and bromotrimethylsilane prepare 4-bromophenol

[0020] Phenol (47.0 mg, 0.50 mmol), bromotrimethylsilane (84.2 mg, 0.55 mmol, 1.1 equiv.), bis-(4-chlorophenyl) sulfoxide (148.5 mg, 0.55 mol) and acetonitrile (1.0 mL), then evacuated, under nitrogen protection, and reacted at 25 °C for 6 h. After the completion of the reaction monitored by GC-MS, filter and wash the filter cake with a small amount of cold acetonitrile, and recover the filter cake as bis-(4-chlorophenyl)sulfide. Add 1M sodium hydroxide (0.6 mL) to the filtrate, then transfer to a separatory funnel and extract with ethyl acetate 5 mL*3, combine the organic layers, spin dry and combine with the filter cake bis-(4-chlorophenyl) obtained above The thioether is combined, that is, a mixture of bis-(4-chlorophenyl)sulfoxide (residue from the reaction) and bis-(4-chlorophenyl)sulfide (reaction product), and then the mixture is completely converted to di- (4-Chlorophenyl) sulfoxide can be us...

Embodiment 2

[0024] Embodiment 2 phenol and bromotrimethylsilane prepare 4-bromophenol

[0025] Phenol (47.0 mg, 0.50 mmol), bromotrimethylsilane (84.2 mg, 0.55 mmol, 1.1 equiv.), bis-(4-methylphenyl) sulfoxide (126.5 mg, 0.55 mol ) and acetonitrile (1.0 mL), then evacuated, under nitrogen protection, and reacted at 25°C for 6 h. After the completion of the reaction was monitored by GC-MS, 1M sodium hydroxide (0.6mL) was added to the solution, then transferred to a separatory funnel and extracted with ethyl acetate 5 mL*3, the organic layers were combined, and the obtained filter cake di-(4 -Tolyl)sulfide and bis-(4-tolyl)sulfoxide (residue from the reaction). The mixture was then completely converted to bis-(4-tolyl)sulfoxide by oxidation, which could be used as an activator in the next bromination reaction of phenolic compounds (90% overall recovery). Add 1M dilute hydrochloric acid to the extracted aqueous phase to adjust the pH to 1, then add 5 mL*3 ethyl acetate again for extraction...

Embodiment 3

[0028] Embodiment 3 phenol and bromotrimethylsilane prepare 4-bromophenol

[0029] Phenol (47.0 mg, 0.50 mmol), bromotrimethylsilane (84.2 mg, 0.55 mmol, 1.1 equiv.), bis-(4-chlorophenyl) sulfoxide (148.5 mg, 0.55 mol) and acetonitrile (1.0 mL), then evacuated, under nitrogen protection, and reacted at 25 °C for 6 h. After the completion of the reaction was monitored by GC-MS, the product was separated and purified by column chromatography (petroleum ether / ethyl acetate = 30 / 1). The separation yield was 90% (selectivity 97 / 3).

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PUM

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Abstract

The invention discloses a high-regioselectivity bromination method for phenol compounds. According to the high-regioselectivity bromination method, bromotrimethylsilane serving as a bromination reagent, aryl sulfoxide serving as an activating agent and the phenol compounds are stirred and react for 1-12 hours at the temperature of 0-50 DEG C in a solvent and under the nitrogen atmosphere, thus high-regioselectivity bromination of the phenol compounds is achieved, and bromophenol compounds are obtained by separating and purifying through filtering, extraction or column chromatography methods. The high-regioselectivity bromination method adopts the aryl sulfoxide as the activating agent, the sulfoxide substituent group is large, on the one hand, regioselectivity of a phenol compound bromination reaction is high, when the hydroxyl para-position of the phenol compounds has no substituent group, a product of para-bromination is obtained in a regioselectivity mode, however when the hydroxylpara-position of the phenol compounds has the substituent group, a product of ortho-bromination is obtained in a regioselectivity mode, on the other hand, by-products can be simultaneously recycled byseparating and purifying through the filtering and extraction methods, and the separating and purifying costs are lowered compared with the column chromatography.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a method for highly regioselective bromination of phenolic compounds. Background technique [0002] Phenols are important synthetic intermediates and are widely used in organic synthesis. At the same time, there are also structural units of phenolic compounds in many active pharmaceutical molecules, so it is of great value to carry out research on the synthesis of phenol derivatives. Brominated phenol can undergo Heck reaction, Suzuki coupling reaction, Ullmann coupling reaction, etc., and can be further converted into structural units with more complex and diverse structures. However, the bromination reaction of phenol still has low regioselectivity and unsatisfactory reaction yields. However, there is still an urgent need to develop a highly regioselective phenol bromination reaction method. [0003] The synthesis methods reported in the literature main...

Claims

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Application Information

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IPC IPC(8): C07C37/62C07C39/27C07C41/22C07C43/253C07C231/12C07C233/25C07C67/307C07C69/84C07C39/38C07C45/63C07C47/565
Inventor 马献涛于静江梦园唐林周秋菊
Owner XINYANG NORMAL UNIVERSITY
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