Center for Molecular Modeling - C. Stevens

Direct Aminolysis of Methyl Esters With Ammonia in Continuous Flow Through Bayesian Optimization

leen — Tue, 13 May 2025 09:53:17 +0000

B. Vandekerckhove, S. Desimpel, B. Ruttens, M. Bocus, W. Temmerman, B. Metten, V. Van Speybroeck, T. Heugebaert, C. Stevens

Reaction Chemistry & Engineering

10, 1887-1896

2025

Abstract

Amides play a crucial role in the pharmaceutical, animal health and agrochemical industry. Despite the availability of various catalytic systems and coupling reagents, many methods suffered from long reaction times and poor atom economy. The direct synthesis of primary amides remained particularly challenging due to the limited availability of suitable nitrogen sources. In this study, continuous flow technology was explored as a process-intensification approach for the direct amidation of methyl esters to produce primary amides. Methanolic ammonia was employed as a nitrogen source to enhance process efficiency while circumventing the limitations of aqueous ammonia and the hazards of gaseous ammonia. Seventeen substrates were screened to assess their aminolysis reactivity under these conditions. As a proof of concept, methyl picolinate was selected for continuous flow optimization using Bayesian Optimization. Therefore, a custom-designed high-pressure, high-temperature continuous flow reactor was utilized to achieve efficient, safe and scalable synthesis (200 °C, 50 bar).

DOI

https://doi.org/10.1039/D5RE00163C

Private attachment

d5re00163c.pdf

The application of porous organic polymers as metal free photocatalysts in organic synthesis

leen — Tue, 19 Mar 2024 07:46:25 +0000

M. Debruyne, P. Van der Voort, V. Van Speybroeck, C. Stevens

Chemistry - A European Journal

2024

Abstract

Concerns about increasing greenhouse gas emissions and their effect on our environment highlight the urgent need for new sustainable technologies. Visible light photocatalysis allows the clean and selective generation of reactive intermediates under mild conditions. The more widespread adoption of the current generation of photocatalysts, particularly those using precious metals, is hampered by drawbacks such as their cost, toxicity, difficult separation, and limited recyclability. This is driving the search for alternatives, such as porous organic polymers (POPs). This new class of materials is made entirely from organic building blocks, can possess high surface area and stability, and has a controllable composition and functionality. This review focuses on the application of POPs as photocatalysts in organic synthesis. For each reaction type, a representative material is discussed, with special attention to the mechanism of the reaction. Additionally, an overview is given, comparing POPs with other classes of photocatalysts, and critical conclusions and future perspectives are provided on this important field.

DOI

http://dx.doi.org/10.1002/chem.202400311

Private attachment

The application of porous organic polymers as metal free photocatalysts in.pdf

Development of porous organic polymers as metal free photocatalysts for the aromatization of N-heterocycles

leen — Thu, 07 Dec 2023 07:12:22 +0000

M. Debruyne, N. Raeymackers, H. Vrielinck, S. Radhakrishnan, E. Breynaert, M. Delaey, A. Laemont, K. Leus, J. Everaert, H. Rijckaert, D. Poelman, R. Morent, N. De Geyter, P. Van der Voort, V. Van Speybroeck, C. Stevens, T.S.A Heugebaert

ChemCatChem

2024

Abstract

Porous organic polymers (POPs), and especially covalent triazine frameworks (CTFs), are being developed as the next generation of metal-free heterogeneous photocatalysts. However, many of the current synthetic routes to obtain these photoactive POPs require expensive monomers and rely on precious metal catalysts, thus hindering their widespread implementation. In this work, a range of POPs was synthesized from simple unfunctionalized aromatic building blocks, through Lewis acidcatalyzed polymerization. The obtained materials were applied, for the first time, as heterogeneous photocatalysts for the aromatization of N-heterocycles. With the use of the most active material, denoted as CTF-Pyr, which consists of photoactive pyrene and triazine moieties, a wide range of pyridines, dihydroquinoline-5-ones, tetrahydroacridine-1,8-diones and pyrazoles were obtained in excellent yields (70-99%). Moreover, these reactions were carried out under very mild conditions using air and at room temperature, highlighting the potential of these materials as catalysts for green transformations.

DOI

https://doi.org/10.1002/cctc.202301205

Private attachment

Development of porous organic polymers as metal free photocatalysts for the aromatization.pdf

Covalent Organic Framework supported Palladium Catalysts

leen — Mon, 26 Sep 2022 08:50:12 +0000

H. Salemi, M. Debruyne, V. Van Speybroeck, P. Van der Voort, M. D'Hooghe, C. Stevens

Journal of Materials Chemistry A

10, 39, 20707-20729

2022

Abstract

Covalent organic frameworks (COFs), as highly porous crystalline structures, are newly emerging materials designed with tuneable features. They have a high potential to be a host to immobilize metal catalysts. The unique property of these materials, such as their high surface area, oriented channels, and heteroatom enrichment, make them promising materials to improve some disadvantages of heterogeneous metal catalysts. In this review, the fabrication and application of Pd anchored COFs as one of the most critical transition-metal catalysts that play a crucial role in a wide range of reactions is summarized.

DOI

https://doi.org/10.1039/D2TA05234B

Private attachment

340-2022-JChemMatA-COF-Pd catalyst.pdf

Porous organic polymers as metal free heterogeneous organocatalysts

leen — Tue, 07 Dec 2021 09:49:31 +0000

M. Debruyne, V. Van Speybroeck, P. Van der Voort, C. Stevens

Green Chemistry

Volume 23, Issue 19, Page 7361-7434

2021

Abstract

Efficient catalysis is essential from a green chemistry perspective. Porous organic polymers (POPs) have recently emerged as highly effective materials for catalytic applications. POPs possess controllable compositions and functionalities, high surface areas and can be very stable. In this review we focus on the application of POPs as metal free heterogeneous organocatalysts, a booming field in green chemistry. Acid, base, combined acid-base and hydrogen bonding catalysis are addressed. In addition, chiral catalysis and CO2 utilization with POPs are discussed. The aim is to provide a comprehensive overview of the field, exploring all different types of POPs as metal free catalysts. Special attention is given to the synthesis conditions to provide the reader with more insight into the construction of these types of materials.

DOI

10.1039/d1gc02319e

Private attachment

d1gc02319e_compressed.pdf

Synthesis of Nitrile-Functionalized Polydentate N-Heterocycles as Building Blocks for Covalent Triazine Frameworks

leen — Tue, 07 Dec 2021 09:35:38 +0000

J. Everaert, M. Debruyne, F. Vandenbussche, K. Van Hecke, T.S.A Heugebaert, P. Van der Voort, V. Van Speybroeck, C. Stevens

Synthesis-Stuttgart

2021

Abstract

Covalent triazine frameworks (CTFs) based on polydentate ligands are highly promising supports to anchor catalytic metal complexes. The modular nature of CTFs allows to tailor the composition, structure, and function to its specific application. Access to a broad range of chelating building blocks is therefore essential. In this respect, we extended the current available set of CTF building blocks with new nitrile-functionalized N-heterocyclic ligands. This paper presents the synthesis of the six ligands which vary in the extent of the aromatic system and the denticity. The new building blocks may help in a rational design of enhanced support materials in catalysis.

DOI

http://dx.doi.org/10.1055/a-1626-5749

Private attachment

a-1626-5749.pdf

Unexpected formation of 2,2-dichloro-N-(chloromethyl)acetamides during attempted Staudinger 2,2-dichloro-β-lactam synthesis

leen — Thu, 14 Oct 2021 12:42:00 +0000

S. Deketelaere, E. Van den Broeck, L. Cools, D. Deturck, H. Naeyaert, K. Van Hecke, C. Stevens, V. Van Speybroeck, M. D'Hooghe

European Journal of Organic Chemistry

2021, 42, 5823-5830

2021

Abstract

In the quest for 3,3-dichloro-β-lactam building blocks, the serendipitous formation of 2,2-dichloro-N-(chloromethyl)acetamides was observed. This peculiar reactivity was investigated in detail, both experimentally and computationally by means of Density Functional Theory (DFT) calculations. 2,2-Dichloro-N-(chloromethyl)acetamides were thus shown to be formed experimentally through reaction of 2,2-dichloroacetyl chloride with glyceraldehyde-derived imines, i. e. (2,2-dimethyl-1,3-dioxolan-4-yl)methanimines, bearing aromatic N-substituents, in the presence as well as in the absence of a base. Deployment of aliphatic imines, however, resulted in complex reaction mixtures, pointing to the importance of a stabilizing aromatic substituent at nitrogen. The DFT results indicate that the substituents can alter the governing equilibria on the one hand and intrinsic barrier heights for the different routes on the other hand, showing that these are controlling the reaction outcome. Furthermore, the 2,2-dichloro-N-(chloromethyl)acetamides proved to be rather unstable in solution and thus difficult to isolate. Nonetheless, their molecular structure was confirmed by means of NMR analysis of several purified analogs and X-ray study of a 4-methoxyphenyl derivative.

DOI

http://dx.doi.org/10.1002/ejoc.202100975

Private attachment

European J Organic Chem - 2021 - Deketelaere - Unexpected Formation of 2 2%u2010Dichloro%u2010N%u2010 chloromethyl acetamides during.pdf

Elucidating the promotional effect of a covalent triazine framework in aerobic oxidation

samuel — Mon, 06 Apr 2020 08:30:23 +0000

S. Abednatanzi, P. Gohari Derakhshandeh, P. Tack, F. Muniz-Miranda, Y-Y Liu, J. Everaert, M. Meledina, F. Vanden Bussche, L. Vincze, C. Stevens, V. Van Speybroeck, H. Vrielinck, F. Callens, K. Leus, P. Van der Voort

Applied Catalysis B: Environmental

269, 118769

2020

DOI

http://dx.doi.org/10.1016/j.apcatb.2020.118769

Private attachment

1-s2.0-S0926337320301843-main.pdf

Electronic properties of heterogenized Ru(II) polypyridyl photoredox complexes on covalent triazine frameworks

kurt — Wed, 13 Mar 2019 07:02:04 +0000

A. De Vos, K. Lejaeghere, F. Muniz-Miranda, C. Stevens, P. Van der Voort, V. Van Speybroeck

Journal of Materials Chemistry A

7, 8433-8442

2019

Abstract

Ru(II) polypyridyl complexes have been successful for a wide range of photoredox applications thanks to their efficient light-induced metal-to-ligand charge transfer. Using the computational framework of density-functional theory, we report how these complexes can be anchored onto covalent triazine frameworks while maintaining their favorable electronic properties. We moreover show that variation of the nitrogen content of the framework linkers or complex ligands endows the heterogenized catalyst with a unique versatility, spanning a wide range of absorption characteristics and redox potentials. By judiciously choosing the catalyst building blocks, it is even possible to selectively guide the charge transfer toward either the scaffold or the accessible pore sites. Rational design of sustainable and efficient photocatalysts thus comes within reach.

DOI

http://dx.doi.org/10.1039/C9TA00573K

Private attachment

C9TA00573K.pdf

Immobilization of Ir(I) complex on Covalent Triazine Frameworks for C-H Borylation Reactions: A Combined Experimental and Computational Study

wim — Mon, 03 Dec 2018 11:17:40 +0000

N. Tahir, F. Muniz-Miranda, J. Everaert, P. Tack, T.S.A Heugebaert, K. Leus, L. Vincze, C. Stevens, V. Van Speybroeck, P. Van der Voort

Journal of Catalysis

371, 135-143

2019

Abstract

Metal-modified covalent triazine frameworks (CTFs) have attracted considerable attention in heterogeneous catalysis due to their strong nitrogen-metal interactions exhibiting superior activity, stability and hence recyclability. Herein, we report on a post-metalation of a bipyridine-based CTFs with an Ir(I) complex for CH borylation of aromatic compounds. Physical characterization of the Ir(I)-based bipyCTF catalyst in combination with density functional theory (DFT) calculations exhibit a high stabilization energy of the Ir-bipy moiety in the frameworks in the presence of B2Pin2. By using B2Pin2 as a boron source, Ir(I)@bipyCTF efficiently catalyzed the CH borylation of various aromatic compounds with excellent activity and good recyclability. In addition, XAS analysis of the Ir(I)@bipyCTF gave clear evidence for the coordination environment of the Ir.

DOI

http://dx.doi.org/10.1016/j.jcat.2019.01.030