Computational study on the synthesis of 1-phenyl-3,4-dihydro-beta-carboline T3P (R)-promoted one-pot formation from tryptamine vs. POCl3-mediated ring closure of N-b-benzoyltryptamine. The first DFT investigation of the Bischler-Napieralski reaction

作者：Abranyi Balogh Peter^*; Volk Balazs; Keglevich Gyorgy; Milen Matyas

来源：Computational and Theoretical Chemistry, 2016, 1097: 48-60.

DOI：10.1016/j.comptc.2016.10.008

• beta-Carbolines
• Bischler-Napieralski reaction
• T3P (R)
• Reaction mechanism
• Quantum chemical calculations

Previously a novel and efficient one-pot method has been developed for the synthesis of 1-substituted-3,4-dihydro-beta-carbolines starting from tryptamine and a wide variety of carboxylic acids. The first reaction step was the acylation of tryptamine leading to the corresponding acyltryptamines, followed by a ring-closure step affording the tricyclic target molecules. In the present paper, possible mechanisms are proposed for the acylation of tryptamine with benzoic acid and for the closure of the beta-carboline ring, including a detailed discussion of the effect of the T3P (R) reagent. In order to compare the innovative T3P (R)-promoted method with the traditional POCl3-promoted one, mechanistic computations have been performed for both methods. The computed mechanistic pathways explain why less than two equivalents of the T3P (R) reagent are sufficient for the two consecutive reaction steps and a parallelism is shown between the energetics of the T3P (R)-disruption and the biological energy storage of ATP. It can also be understood, why a higher temperature and a longer reaction time are required for the T3P (R)-promoted synthesis. Although the history of the Bischler-Napieralski reaction goes back more than 120 years, it is the first time that the reaction is studied by DFT quantum chemical calculations.

• 出版日期2016-12-1