Schnyder A, Beller M, Mehltretter G, Nsenda T, Studer M, Indolese A F
Solvias AG, Klybeckstrasse 191, CH-4002 Basel, Switzerland.
J Org Chem. 2001 Jun 15;66(12):4311-5. doi: 10.1021/jo015577t.
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 degrees C) 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.
以甲酰胺为胺源，通过钯催化芳基卤化物的氨羰基化反应，以高产率（70 - 90%）制备了伯芳酰胺。该反应需要钯催化剂与亲核路易斯碱（如咪唑或4 - （二甲基氨基）吡啶（DMAP））结合使用。芳基、杂芳基以及乙烯基溴化物和氯化物在温和条件（5巴，120℃）下，使用1 mol%的钯 - 膦配合物可转化为伯酰胺。在二氧六环中使用三苯基膦作为配体、DMAP作为碱可获得最佳结果。对于活性芳基溴化物，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高达8:1，以稳定催化剂并实现完全转化。详细研究了催化剂、碱、溶剂、压力和温度的影响。通过分离和鉴定反应中间体，阐明了反应机理。此外，使用N - 甲基甲酰胺和N，N - 二甲基甲酰胺作为胺源，通过相同方法制备了甲基酰胺和二甲基酰胺。
