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Study On The Bromination Of Aromatic Ring And Benzylic ?-H

Posted on:2018-01-12Degree:MasterType:Thesis
Country:ChinaCandidate:Y F ChenFull Text:PDF
GTID:2321330518975101Subject:Organic Chemistry
Abstract/Summary:PDF Full Text Request
The bromination of aromatic ring and benzylic a-H is one of the most basic synthetic reactions and has an extremely important application in the synthesis of pharmaceuticals and natural products.Although the bromination of aromatic compounds has been reported a lot,an economical,efficient,highly selective,safe and environmentally bromination process is still an important goal in the field of pharmaceutical production.In this paper,with NaBrO3-NaBr-H2SO4 as bromination reagent,the bromination of aromatic rings and benzylic a-H was investigated.And the research results were applied to the synthesis of two important pharmaceutical intermediates.The paper is divided into the following three parts.Firstly,the bromination of aromatic ring and benzylic a-H was investigated:The conditions of electrophilic bromination reaction on aromatic ring were optimized with NaBrO3-NaBr-H2SO4 as bromination reagent.The results showe that the electron donative substituents on the aromatic ring are favorable for the electrophilic bromination reaction,and the reaction has excellent selectivity,it can be controlled well in the monobromo-or dibromo stage.However,when the aromatic ring has an electron-withdrawing substituent,the electrophilic bromination rate is slowed down and the yield is reduced.The bromination of benzylic a-H was also achieved by the addition of radical initiators and optimization of the reation conditions.Even for the toluene with an electron donative group(eg,1-methoxy-4-methylbenzene),the bromination of benzylic a-H can still give an ideal yield.Then one pot reaction of aromation ring and benzylic bromation was achieved,which provided a simple and safe method for the synthesis of polybrominated aromatic compounds.Secondly,the syntheis of 4-(methylsulfonyl)benzaldehyde(an important intermediate of thiamphenicol)was conducted.With NaBrO3-HBr-H2SO4 as bromination reagent,azobisisobutyronitrile and dibenzoyl peroxide as radical initiators and 1,2-dichloroethane as solvent,the 1-(dibromomethyl)-4-(methylsulfonyl)benzene was obtained by the benzylic bromination of 1-methyl-4-(methylsulfonyl)benzene.Then,1-(dibromomethyl)-4-(methylsulfonyl)benzene was hydrolyzed to give 4-(methylsulfonyl)benzaldehyde in 28%hydrobromic acid,the total yield was up to 76%.It provided a simple,safe and lower cost process for the industrial production of 4-(methylsulfonyl)benzaldehyde.Thirdly,the preparation of 1-bromo-2-bromomethyl-4,5-dimethoxybenzene(an important intermediate of pinaverium bromide)was studied.With NaBrO3-NaBr-H2SO4 as bromination reagent,2,2'-azobis-(2,4-dimethylvaleronitrile)as radical initiators and carbon tetrachloride as the solvent,1-bromo-2-bromomethyl-4.5-dimethoxybenzene was prepared in high yield by the one pot bromination of 3,4-dimethoxytoluene.The advantages of this method are the use of cheap and easily available materials,simple and safe operation.
Keywords/Search Tags:Bromination, 4-(Methylsulfonyl)benzaldehyde, Thiamphenicol, Pinaverium bromide, Pharmaceutical intermediates
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