Synthesis of primary aromatic amides by aminocarbonylation of aryl halides using formamide as an ammonia synthon
Synthesis of primary aromatic amides by aminocarbonylation of aryl halides using formamide as an ammonia synthon
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DOI：
10.1021/jo015577t
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发表时间：
2001-06-15
影响因子：
3.6
通讯作者：
Indolese, AF
中科院分区：
文献类型：
--
作者：
Schnyder, A;Beller, M;Indolese, AF
以甲酰胺为胺源，通过钯催化的芳基卤化物的氨甲基化反应，高产率地(70-90%)合成了伯芳胺。这些反应需要钯催化剂和亲核的Lewis碱(如咪唑或4-二甲氨基)吡啶(DMAP)相结合。在温和的条件下(5bar，120℃)，用1mol%的钯-膦络合物将芳基、杂芳基和乙烯基溴化物和氯化物转化为伯胺。在二氧六环中，以三苯基膦为配体，DMAP为碱，得到了最好的反应结果。对于活化的芳基溴化物，膦与钯的比例为2：1就足够了，但活性较低的芳基溴化物或芳基氯化物需要配体与钯的比例达到8：1，才能稳定催化剂并实现完全转化。考察了催化剂、碱、溶剂、压力、温度等因素对反应的影响。通过对反应中间产物的分离和鉴定，可以阐明反应机理。另外，以N-甲基甲酰胺和N，N-二甲基甲酰胺为胺源，用相同的方法合成了甲胺和二甲胺。
Primary aromatic amides were prepared by a palladium-catalyzed aminocarbonylation reaction of aryl halides in high yields (70-90%) using formamide as the amine source. The reactions require a palladium catalyst in combination with a nucleophilic Lewis base such as imidazole or 4-(dimethylamino)pyridine (DMAP). Aryl, heteroaryl, and vinyl bromides and chlorides were converted to the primary amides under mild conditions (5 bar, 120 degreesC) using 1 mol % of a palladium-phosphine complex. Best results were obtained in dioxane using triphenylphosphine as the ligand and DMAP as the base. For activated aryl bromides, a phosphine-to-palladium ratio of 2:1 was sufficient, but less reactive aryl bromides or aryl chlorides required ligand-to-palladium ratios up to 8:1 in order to stabilize the catalyst and achieve full conversion. The influence of catalyst, base, solvent, pressure, and temperature was studied in detail. The mechanism of the reaction could be clarified by isolating and identifying the reaction intermediates. In addition, methylamides and dimethylamides were prepared by the same method using N-methylformamide and N,N-dimethylformamide as the amine source.