Lim Felicia Phei Lin, Tan Lin Yuing, Tiekink Edward R T, Dolzhenko Anton V
School of Pharmacy, Monash University Malaysia Jalan Lagoon Selatan, Bandar Sunway Selangor Darul Ehsan 47500 Malaysia
Research Centre for Crystalline Materials, School of Science and Technology, Sunway University Bandar Sunway Selangor Darul Ehsan 47500 Malaysia.
RSC Adv. 2018 Jun 19;8(40):22351-22360. doi: 10.1039/c8ra04576c.
Two complementary pathways for the preparation of -substituted 3-(5-amino-1-1,2,4-triazol-3-yl)propanamides (5) were proposed and successfully realized in the synthesis of 20 representative examples. These methods use the same types of starting materials . succinic anhydride, aminoguanidine hydrochloride, and a variety of amines. The choice of the pathway and sequence of the introduction of reagents to the reaction depended on the amine nucleophilicity. The first pathway started with the preparation of -guanidinosuccinimide, which then reacted with amines under microwave irradiation to afford 5. The desired products were successfully obtained in the reaction with aliphatic amines (primary and secondary) a nucleophilic opening of the succinimide ring and the subsequent recyclization of the 1,2,4-triazole ring. This approach however failed when less nucleophilic aromatic amines were used. Therefore, an alternative pathway, with the initial preparation of -arylsuccinimides and their subsequent reaction with aminoguanidine hydrochloride under microwave irradiation, was applied. The annular prototropic tautomerism in the prepared 1,2,4-triazoles 5 was studied using NMR spectroscopy and X-ray crystallography.
提出了两种互补的方法来制备β-取代的3-(5-氨基-1,2,4-三唑-3-基)丙酰胺(5)，并在20个代表性实例的合成中成功实现。这些方法使用相同类型的起始原料，即琥珀酸酐、氨基胍盐酸盐和各种胺。反应中试剂引入的途径和顺序的选择取决于胺的亲核性。第一种方法是先制备β-胍基琥珀酰亚胺，然后在微波辐射下与胺反应得到5。与脂肪族胺（伯胺和仲胺）反应时成功得到了所需产物，这是通过琥珀酰亚胺环的亲核开环以及随后1,2,4-三唑环的环化实现的。然而，当使用亲核性较弱的芳香族胺时，这种方法失败了。因此，采用了另一种方法，即先制备β-芳基琥珀酰亚胺，然后在微波辐射下与氨基胍盐酸盐反应。使用核磁共振光谱和X射线晶体学研究了所制备的1,2,4-三唑5中的环状质子互变异构。
