Kinetics of Aqueous Media Reactions via Ab Initio Enhanced Molecular Dynamics: The Case of Urea Decomposition

Polino, Daniela; Parrinello, Michele

doi:10.1021/acs.jpcb.9b05271

Cited by 16 publications

(15 citation statements)

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“…Both the isocyanate and hydrolysis reaction mechanisms (Reactions B and C and Scheme 1 ) involve water. Water is obviously important for hydrolysis, and water is known to favor the formation of isocyanic acid and ammonia because of its assistance to the proton transfer between the amines of the urea [ 67 ]. The moderate dependence on water content indicates that water does promote the reaction, but it is not a requirement (as it would be for hydrolysis), consistent with an isocyanic acid intermediate as the dominant reaction mechanism under our experimental conditions.…”

Section: Resultsmentioning

confidence: 99%

“…This carbamic acid can either react with an amino group to form ureido or decompose to NH 3 and CO 2 . Under our reaction conditions, ureido formation is expected to proceed predominantly through an isocyanic acid intermediate formed in situ from the decomposition of urea ( Scheme 1 b) [ 21 , 67 , 68 ].…”

Section: Introductionmentioning

confidence: 99%

“…The reaction can follow two mechanisms: in situ formation of isocyanic acid or urea hydrolysis. The isocyanate route (Scheme 1b) is considered to be the dominant mechanism when the reaction is carried out without catalysts [67,68]. The presence of water promotes Reaction B (Scheme 1b), via in situ formation of isocyanic acid (HNCO), through a hydrogen-shuttling mechanism, where the water assists the urea decomposition and favors the proton transfer between its two amino groups, promoting the formation of HNCO and NH 3 [20,67,68].…”

Section: Introductionmentioning

confidence: 99%

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Ureido Functionalization through Amine-Urea Transamidation under Mild Reaction Conditions

Guerrero‐Alburquerque

Zhao

Rentsch

et al. 2021

Polymers

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Ureido-functionalized compounds play an indispensable role in important biochemical processes, as well as chemical synthesis and production. Isocyanates, and KOCN in particular, are the preferred reagents for the ureido functionalization of amine-bearing compounds. In this study, we evaluate the potential of urea as a reagent to graft ureido groups onto amines at relatively low temperatures (<100 °C) in aqueous media. Urea is an inexpensive, non-toxic and biocompatible potential alternative to KOCN for ureido functionalization. From as early as 1864, urea was the go-to reagent for polyurea polycondensation, before falling into disuse after the advent of isocyanate chemistry. We systematically re-investigate the advantages and disadvantages of urea for amine transamidation. High ureido-functionalization conversion was obtained for a wide range of substrates, including primary and secondary amines and amino acids. Reaction times are nearly independent of substrate and pH, but excess urea is required for practically feasible reaction rates. Near full conversion of amines into ureido can be achieved within 10 h at 90 °C and within 24 h at 80 °C, and much slower reaction rates were determined at lower temperatures. The importance of the urea/amine ratio and the temperature dependence of the reaction rates indicate that urea decomposition into an isocyanic acid or a carbamate intermediate is the rate-limiting step. The presence of water leads to a modest increase in reaction rates, but the full conversion of amino groups into ureido groups is also possible in the absence of water in neat alcohol, consistent with a reaction mechanism mediated by an isocyanic acid intermediate (where the water assists in the proton transfer). Hence, the reaction with urea avoids the use of toxic isocyanate reagents by in situ generation of the reactive isocyanate intermediate, but the requirement to separate the excess urea from the reaction product remains a major disadvantage.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ureido Functionalization through Amine-Urea Transamidation under Mild Reaction Conditions

Guerrero‐Alburquerque

Zhao

Rentsch

et al. 2021

Polymers

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“…[1,2,3,4,5,6,7,8,9,10,11,12,13] Following Dewyer et al [12] these methods can be categorized into four categories: 1) encoding mechanistic steps, 2) generate transition state (TS) guesses, 3) generate intermediates using graph theory, and 4) generate driving coordinates. Recently, quantum chemical meta-dynamics based approaches [14,10,9,13,11] has emerged as a fifth category. Most of these approaches are rather computationally expensive so they have generally been applied to relatively small molecules with less than ten heavy atoms.…”

Section: Introductionmentioning

confidence: 99%

Fast and Automated Identification of Reactions with Low Barriers: The Decomposition of 3-Hydroperoxypropanal

Rasmussen¹,

Madsen²,

Jensen

2021

Preprint

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We show how fast semiempirical QM methods can be used to significantly decrease the computational expense for automated reaction mechanism discovery, using two different method for generating reaction products: graph-based systematic enumeration of all possible products and the meta-dynamics approach by Grimme (J. Chem. Theory. Comput. 2019Comput. , 15, 2847. We test the two approaches on the low-barrier reactions of 3-hydroperoxypropanal, which have been studied by a large variety of reaction discovery approaches and therefore provides a good benchmark. By using PM3 and GFN2-xTB for reaction energy and barrier screening the systematic approach identifies 64 reactions (out of 27,577 possible reactions) for DFT refinement, which in turn identifies the three reactions with lowest barriers plus a previously undiscovered reaction. With optimized hyperparameters meta-dynamics followed by PM3/GFN2-xTB-based screening identifies 15 reactions for DFT refinement, which in turn identifies the three reactions with lowest barrier. The number of DFT refinements can be further reduced to as little as six for both approaches by first verifying the transition states with GFN1-xTB. The main conclusion is that the semiempirical methods are accurate and fast enough to automatically identify promising candidates for DFT refinement for the low barrier reactions of 3-hydroperoxypropanal in about 15-30 minutes using relatively modest computational resources.

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“…However, several very promising methodologies have been developed to automate the discovery of reaction mechanisms using QM. [1,2,3,4,5,6,7,8,9,10,11,12,13] Following Dewyer et al [12] these methods can be categorized into four categories: 1) encoding mechanistic steps, 2) generate transition state (TS) guesses, 3) generate intermediates using graph theory, and 4) generate driving coordinates. Recently, quantum chemical meta-dynamics based approaches [14,10,9,13,11] has emerged as a fifth category.…”

Section: Introductionmentioning

confidence: 99%

Fast and Automated Identification of Reactions with Low Barriers: The Decomposition of 3-Hydroperoxypropanal

Rasmussen¹,

Madsen²,

Jensen

2021

Preprint

View full text Add to dashboard Cite

We show how fast semiempirical QM methods can be used to significantly decrease the CPU requirements for automated reaction mechanism discovery, using two different method for generating reaction products: graph-based systematic enumeration of all possible products and the meta-dynamics approach by Grimme (J. Chem. Theory. Comput. 2019, 15, 2847). We test the two approaches on the low-barrier reactions of 3-hydroperoxypropanal, which have been studied by a large variety of reaction discovery approaches and therefore provides a good benchmark. By using PM3 and GFN2-xTB for reaction energy and barrier screening the systematic approach identifies 64 reactions (out of 27,577 possible reactions) for DFT refinement, which in turn identifies the three reactions with lowest barriers plus a previously undiscovered reaction. With optimised hyperparameters meta-dynamics followed by PM3/GFN2-xTB-based screening identifies 15 reactions for DFT refinement, which in turn identifies the three reactions with lowest barrier. The number of DFT refinements can be further reduced to as little as six for both approaches by first verifying the transition states with GFN1-xTB. The main conclusion is that the semiempirical methods are accurate and fast enough to automatically identify promising candidates for DFT refinement for the low barrier reactions of 3-hydroperoxypropanal in about 15-30 minutes using relatively modest computational resources.

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Kinetics of Aqueous Media Reactions via Ab Initio Enhanced Molecular Dynamics: The Case of Urea Decomposition

Cited by 16 publications

References 46 publications

Ureido Functionalization through Amine-Urea Transamidation under Mild Reaction Conditions

Ureido Functionalization through Amine-Urea Transamidation under Mild Reaction Conditions

Fast and Automated Identification of Reactions with Low Barriers: The Decomposition of 3-Hydroperoxypropanal

Fast and Automated Identification of Reactions with Low Barriers: The Decomposition of 3-Hydroperoxypropanal

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