N-杂环卡宾催化芳香醛与芳香卤代物亲核酰基化反应研究
发布时间：2018-09-01 15:09
【摘要】：二苯甲酮类化合物是一类重要的精细化学品和有机合成中间体。传统的二苯甲酮类化合物主要由亲电酰基化反应和过渡金属催化偶联反应合成,反应底物受到一定的限制,且需要使用大量的路易斯酸或者过渡金属配合物作为催化剂,对环境污染严重。N-杂环卡宾作为一种有机小分子催化剂,能够催化芳香醛与芳香卤代物的亲核酰基化反应,为合成二苯甲酮类化合物提供了一条新的途径。合成了两种类型的N-杂环卡宾前体:咪唑类卡宾前体和噻唑类卡宾前体。其中,咪唑类卡宾前体根据所含阴离子不同分为四氟硼酸盐类和六氟磷酸盐类两种类型。利用红外光谱、核磁共振氢谱等技术对合成的N-杂环卡宾前体进行结构确定。将合成的N-杂环卡宾用于催化单取代芳香醛与对氟硝基苯的亲核酰基化反应。使用对氟苯甲醛与对氟硝基苯作为模型反应底物,对卡宾前体种类、时间、温度、催化剂用量等因素进行优化,确定了反应的最佳条件:以1-丁基-3-甲基咪唑四氟硼酸盐为卡宾前体,反应时间为1 h,反应温度为0℃,DMF为溶剂,催化剂用量为反应物用量的20 mmol%。考察了反应物上不同取代基团对反应的影响;同时,考察了咪唑类卡宾前体的循环使用情况。将合成的N-杂环卡宾用于催化单或双卤代芳香醛与3,4-二氟硝基苯的亲核酰基化反应。使用2-氟苯甲醛与3,4-二氟硝基苯作为模型反应底物,对卡宾前体种类、时间、温度、催化剂用量等条件进行优化,确定了反应的最佳条件:以1-丁基-3-甲基咪唑四氟硼酸盐为卡宾前体,反应时间为1 h,反应温度为0℃,DMF为溶剂,催化剂用量为反应物用量的20 mmol%。在最佳条件下,催化2-氟苯甲醛、2,4-二氟苯甲醛、2,5-二氟苯甲醛、2,6-二氟苯甲醛分别与3,4-二氟硝基苯反应,反应产率分别为76%、42%、42%和32%。氧杂蒽酮是一类重要的具有生物活性的天然产物。本文提供了一条合成氧杂蒽酮的新思路:首先N-杂环卡宾催化邻甲氧基苯甲醛与3,4-二氟硝基苯的亲核酰基化反应,生成邻位含有甲氧基的二苯甲酮;然后含甲氧基的二苯甲酮发生去甲基化反应,将二苯甲酮的甲氧基转化为羟基;最后发生分子内环化反应生成氧杂蒽酮。使用1,3-二甲基咪唑碘盐作为卡宾前体,分别催化2-甲氧基苯甲醛、2,4-二甲氧基苯甲醛、2,6-二甲氧基苯甲醛和2-甲氧基-5-溴苯甲醛与3,4-二氟硝基苯的反应,反应产率分别为63%、75%、42%和65%。对4-硝基-2'-甲氧基-2-氟二苯甲酮、4-硝基-2',4'-甲氧基-2-氟二苯甲酮和4-硝基-2'-甲氧基-2-氟-5'-溴二苯甲酮进行脱甲基化处理,反应产率分别为52%、85%和60%。在碳酸铯的作用下,脱甲基化的产物4-硝基-2'-羟基-2-氟-二苯甲酮、4-硝基-2'-羟基-2-氟二苯甲酮、4'-硝基-2-羟基'-2-氟-5-溴二苯甲酮发生成环反应,得到相应的氧杂蒽酮,反应产率均在92%左右。
[Abstract]:Benzophenone compounds are an important class of fine chemicals and organic synthesis intermediates. The traditional benzophenone compounds are mainly synthesized by electrophilic acylation reaction and transition metal catalyzed coupling reaction. The reaction substrate is limited and a large number of Lewis acid or transition metal complexes are used as catalysts. N-heterocyclic carbene, as a small organic catalyst, can catalyze the nucleophilic acylation of aromatic aldehydes with aromatic halides, which provides a new way for the synthesis of benzophenone compounds. Two types of N- heterocyclic carbene precursors were synthesized: imidazole carbene precursors and thiazole carbenes precursors. Among them, imidazole carbene precursors are divided into tetrafluoroborate salt and hexafluorophosphate salt according to the anions contained. The structure of the synthesized N- heterocyclic carbene precursor was determined by infrared spectroscopy and nuclear magnetic resonance spectroscopy. The synthesized N-heterocyclic carbene was used to catalyze the nucleophilic acylation of monosubstituted aromatic aldehydes with p-fluoronitrobenzene. Using p-fluorobenzaldehyde and p-fluoronitrobenzene as the model substrate, the kinds of carbene precursors, time, temperature, amount of catalyst and other factors were optimized. The optimum reaction conditions were determined as follows: 1 Ding Ji 3 methyl imidazolium tetrafluoroborate was used as carbene precursor, the reaction time was 1 h, the reaction temperature was 0 鈩，
本文编号：2217570
[Abstract]:Benzophenone compounds are an important class of fine chemicals and organic synthesis intermediates. The traditional benzophenone compounds are mainly synthesized by electrophilic acylation reaction and transition metal catalyzed coupling reaction. The reaction substrate is limited and a large number of Lewis acid or transition metal complexes are used as catalysts. N-heterocyclic carbene, as a small organic catalyst, can catalyze the nucleophilic acylation of aromatic aldehydes with aromatic halides, which provides a new way for the synthesis of benzophenone compounds. Two types of N- heterocyclic carbene precursors were synthesized: imidazole carbene precursors and thiazole carbenes precursors. Among them, imidazole carbene precursors are divided into tetrafluoroborate salt and hexafluorophosphate salt according to the anions contained. The structure of the synthesized N- heterocyclic carbene precursor was determined by infrared spectroscopy and nuclear magnetic resonance spectroscopy. The synthesized N-heterocyclic carbene was used to catalyze the nucleophilic acylation of monosubstituted aromatic aldehydes with p-fluoronitrobenzene. Using p-fluorobenzaldehyde and p-fluoronitrobenzene as the model substrate, the kinds of carbene precursors, time, temperature, amount of catalyst and other factors were optimized. The optimum reaction conditions were determined as follows: 1 Ding Ji 3 methyl imidazolium tetrafluoroborate was used as carbene precursor, the reaction time was 1 h, the reaction temperature was 0 鈩，
本文编号：2217570
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