【作者】 林霞；

【导师】 肖孝辉；

【作者基本信息】 浙江师范大学 ， 有机化学， 2021， 硕士

【摘要】 含溴有机化合物广泛应用于医药、农药以及各类助剂,也是重要的有机合成中间体。常用的溴试剂包括液溴、N-溴代丁二酰亚胺（NBS）、1,3-二溴-5,5-二甲基海因（DBDMH）等。由于液溴毒性和腐蚀性大,NBS、DBDMH等溴试剂使用成本高,因此,发展一种安全、经济的含溴有机化合物的制备工艺依然是工业化生产研究的重要课题之一。本文主要探讨通过氧化剂氧化溴负离子原位形成的溴制备4-溴-N,N-二甲基苯胺、邻二溴代物、（1-溴乙基）苯、（1,1-二溴乙基）苯、（1,1,2-三溴乙基）苯等重要中间体的工艺。1、4-溴-N,N-二甲基苯胺的制备工艺研究:发现以乙酸乙酯与水组成的双相体系为溶剂,在过量的酸作用下,双氧水氧化溴化钠原位形成的溴可以选择性地与N,N-二甲基苯胺反应得到4-溴-N,N-二甲基苯胺,优化反应条件后将该反应放大至1 mol（121 g）,4-溴-N,N-二甲基苯胺的产率可达88%。该方法具有过程操作简单、安全,选择性高,放大稳定性好等优点。2、邻二溴代物的制备工艺研究:在硫酸作用下,NaBrO₃与Na Br反应原位形成的溴可以与烯烃（炔烃）进行亲电加成反应,得到邻二溴代物,反应选择性好,底物适用范围宽;以（E）-2,3-二溴-2-丁烯-1,4-二醇的制备为例,进行了放大实验（1.2 mol,103 g）,产物收率稳定,重现性好,说明该反应该工艺具有较好的产业化前景。3、乙基苯侧链C-H溴代产物的制备工艺研究:在引发剂作用下,NaBrO₃、NaBr与H₂SO₄反应原位生成的溴可以与乙基苯侧链C-H进行自由基取代反应,通过控制NaBrO₃、Na Br和H₂SO₄的用量,可以选择性地得到（1-溴乙基）苯、（1,1-二溴乙基）苯和（1,1,2-三溴乙基）苯;所得溴代产物在碱的作用下消除可以分别得到乙烯基苯、乙炔基苯和（2-溴乙炔基）苯;（1,1-二溴乙基）苯和（1,1,2-三溴乙基）苯在40%氢溴酸中水解可以得到相应的苯乙酮和α-溴代苯乙酮。以3-硝基乙基苯为原料,通过溴代反应制备得到（1,1-二溴乙基）-3-硝基苯,然后在碱的作用下消除得到1-乙炔基-3硝基苯,反应放大至0.9 mol（136.5 g）的投料量,两步反应总收率达到77%。更多还原

【Abstract】 Organic compounds containing bromine element are widely used in medicine,pesticides and all kinds of industrial additives,and are also important intermediates in organic synthesis.Commonly used bromination reagents include bromine,N-bromosuccinimide（NBS）,1,3-dibromo-5,5-dimethylhydantoin（DBDMH）,etc.Because of the high toxicity and corrosion of bromine and the high cost of bromination reagents such as NBS and DBDMH,it is very important to develop a safe and economical process for the organic compounds containing bromine element.The preparation of 4-bromo-N,N-dimethylaniline,1,2-dibromoalkanes,1,2-dibromoalkenes,（1-bromoethyl）benzene,（1,1-dibromoethyl）benzene and（1,1,2-tribromoethyl）benzene were described in this paper.Firstly,the preparation of 4-bromo-N,N-dimethylaniline was investigated.With the mixture of ethyl acetate and water as solvent,the 4-bromo-N,N-dimethylaniline can be prepared by the reaction of N,N-dimethylaniline with bromine which was formed in situ via the REDOX reaction of Na Br,H₂O₂and excess acid.Under optimized conditions,the yield of 4-bromo-N,N-dimethylaniline reached 88%when the reaction was amplified to 1 mol（121 g）.This method has the advantages of simple operation,safety,high selectivity and good process stability.Secondly,the preparation of 1,2-dibromoalkanes（or 1,2-dibromoalkenes）were studied.In the presence of H₂SO₄,1,2-dibromoalkanes（or 1,2-dibromoalkenes）were obtained by the electrophilic addition recation of alkenes（or alkynes）with the bromine formed in situ via the REDOX reaction of NaBrand NaBrO₃.The reaction has good selectivity and wide application range.The amplification experiment of（E）-2,3-dibromo-2-butene-1,4-diol（1.2 mol,103 g）proved that the reproducibility of the process was good and the yield was stable,it shows that the process has a good industrialization prospect.Thirdly,the synthesis of（1-bromoethyl）benzene、（1,1-dibromoethyl）benzene and（1,1,2-tribromoethy）benzene were studied.In the presence of AIBN,the bromine generated in-situ by the reaction of NaBrO₃,NaBrand H₂SO₄can react with ethylbenzene.By controlling the dosage of NaBrO₃-Na Br-H₂SO₄,（1-bromoethyl）benzene,（1,1-dibromoethyl）benzene and（1,1,2-tribromoethyl）benzene can be selectively obtained.The brominated products can be eliminated by alkali to give vinylbenzene,ethynylbenzene and（2-bromoethynyl）benzene,respectively.Hydrolysis of（1,1-dibromoethyl）benzene and（1,1,2-tribromoethyl）benzene in 40%hydrobromic acid yields the corresponding acetophenone andα-bromoacetophenone.Using 3-nitroethylbenzene（0.9 mol,136.5 g）as raw material,the total yield of1-ethyny-3-nitrobenzene was 77%after bromination and elimination reaction.更多还原