High-regioselectivity bromination method for phenol compounds

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...

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 bromide, ammonium bromide, etc.) under the action of excess oxidant ( J. Org. Chem. , 1999, 64, 1191; J. Org. Chem., 2002,67 , 4487; Tetrahedron Lett. , 2008, 49 1729)

Since the reaction mechanism is that bromide and oxidant are converted into bromine electrophile in the reaction system and then participate in the reaction, the above problems still exist and the use of excessive oxidant leads to many by-products and great environmental pollution.

In 2017, Togni reported the regioselective bromination reaction of phenolic compounds using trimethylbromosilane as bromination reagent and dimethyl sulfoxide as activator, but the selectivity of the reaction was not high (88 / 12 ), separation and purification are difficult, and the by-product of the reaction, dimethyl sulfide, has a di-odor smell, which is inconvenient to recycle

Therefore, due to the limitation of the mechanism, the existing methods still have many shortcomings, which need to be improved urgently.