Computational study on the synthesis of 1-phenyl-3,4-dihydro-β-carboline: T3P®-promoted one-pot formation from tryptamine vs. POCl3-mediated ring closure of Nb-benzoyltryptamine. The first DFT investigation of the Bischler-Napieralski reaction

Péter Ábrányi-Balogh, Balázs Volk, G. Keglevich, Mátyás Milen

Research output: Article

2 Citations (Scopus)

Abstract

Previously a novel and efficient one-pot method has been developed for the synthesis of 1-substituted-3,4-dihydro-β-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 β-carboline ring, including a detailed discussion of the effect of the T3P® reagent. In order to compare the innovative T3P®-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® reagent are sufficient for the two consecutive reaction steps and a parallelism is shown between the energetics of the T3P®-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®-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.

Original languageEnglish
Pages (from-to)48-60
Number of pages13
JournalComputational and Theoretical Chemistry
Volume1097
DOIs
Publication statusPublished - dec. 1 2016

Fingerprint

tryptamines
Carbolines
Discrete Fourier transforms
closures
Acylation
acylation
rings
synthesis
reagents
Benzoic Acid
Carboxylic Acids
Energy storage
adenosine triphosphate
benzoic acid
energy storage
Adenosine Triphosphate
History
reaction time
carboxylic acids
Molecules

ASJC Scopus subject areas

  • Biochemistry
  • Condensed Matter Physics
  • Physical and Theoretical Chemistry

Cite this

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title = "Computational study on the synthesis of 1-phenyl-3,4-dihydro-β-carboline: T3P{\circledR}-promoted one-pot formation from tryptamine vs. POCl3-mediated ring closure of Nb-benzoyltryptamine. The first DFT investigation of the Bischler-Napieralski reaction",
abstract = "Previously a novel and efficient one-pot method has been developed for the synthesis of 1-substituted-3,4-dihydro-β-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 β-carboline ring, including a detailed discussion of the effect of the T3P{\circledR} reagent. In order to compare the innovative T3P{\circledR}-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{\circledR} reagent are sufficient for the two consecutive reaction steps and a parallelism is shown between the energetics of the T3P{\circledR}-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{\circledR}-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.",
keywords = "Bischler-Napieralski reaction, Quantum chemical calculations, Reaction mechanism, T3P{\circledR}, β-Carbolines",
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T1 - Computational study on the synthesis of 1-phenyl-3,4-dihydro-β-carboline

T2 - T3P®-promoted one-pot formation from tryptamine vs. POCl3-mediated ring closure of Nb-benzoyltryptamine. The first DFT investigation of the Bischler-Napieralski reaction

AU - Ábrányi-Balogh, Péter

AU - Volk, Balázs

AU - Keglevich, G.

AU - Milen, Mátyás

PY - 2016/12/1

Y1 - 2016/12/1

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AB - Previously a novel and efficient one-pot method has been developed for the synthesis of 1-substituted-3,4-dihydro-β-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 β-carboline ring, including a detailed discussion of the effect of the T3P® reagent. In order to compare the innovative T3P®-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® reagent are sufficient for the two consecutive reaction steps and a parallelism is shown between the energetics of the T3P®-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®-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.

KW - Bischler-Napieralski reaction

KW - Quantum chemical calculations

KW - Reaction mechanism

KW - T3P®

KW - β-Carbolines

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