Ab initio and DFT study of molecular structure and tautomerism of 2-amino-2-imidazoline, 2-amino-2-oxazoline and 2-amino-2-thiazoline

Remko, Milan; Walsh, Owen A.; Richards, W. Graham

doi:10.1016/s0009-2614(01)00104-x

Cited by 34 publications

(7 citation statements)

References 25 publications

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“…In our proposed mechanism ( Figure 4 ), the reaction generates a monourea 3 or bis-urea 4 , which slowly cyclize to form the nucleophilic 2-iminooxazolidines 5 and 6 . These intermediates likely exist as a mixture of tautomers and stereoisomers 53 but react further to form macrocycles only in the Z configurations, which allow for a stabilizing intramolecular hydrogen bond in the final product. 54 Macrocycle 1 is produced by the homocoupling of 5 , while its isomer 2 results from the addition of 6 to a second equivalent of diisocyanate.…”

Section: Resultsmentioning

confidence: 99%

High-Yielding Flow Synthesis of a Macrocyclic Molecular Hinge

et al. 2021

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Many molecular machines are built from modular components with well-defined motile capabilities, such as axles and wheels. Hinges are particularly useful, as they provide the minimum flexibility needed for a simple and pronounced conformational change. Compounds with multiple stable conformers are common, but molecular hinges almost exclusively operate via dihedral rotations rather than truly hinge-like clamping mechanisms. An ideal molecular hinge would better reproduce the behavior of hinged devices, such as gates and tweezers, while remaining soluble, scalable, and synthetically versatile. Herein, we describe two isomeric macrocycles with clamp-like open and closed geometries, which crystallize as separate polymorphs but interconvert freely in solution. An unusual one-pot addition cyclization reaction was used to produce the macrocycles on a multigram scale from inexpensive reagents, without supramolecular templating or high-dilution conditions. Using mechanistic information from NMR kinetic studies and at-line mass spectrometry, we developed a semicontinuous flow synthesis with maximum conversions of 85–93% and over 80% selectivity for a single isomer. The macrocycles feature voids that are sterically protected from guests, including reactive species such as fluoride ions, and could therefore serve as chemically inert hinges for adaptive supramolecular receptors and flexible porous materials.

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Section: Resultsmentioning

confidence: 99%

High-Yielding Flow Synthesis of a Macrocyclic Molecular Hinge

et al. 2021

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“…For example, the energy differences between IA and IB, IIA and IIB, and IIIA and IIIB are 2.82, 1.73, and 0.94 kJ/mol, respectively. Of course, placing such a system with different H-bonding strength into a cavity within a dielectric medium does not represent the realistic situation in the biological medium as suggested by Ramek et al, the more extensive theoretical investigations on glycine amide in aqueous solution are in progress.…”

Section: Resultsmentioning

confidence: 99%

Conformational Study of Glycine Amide Using Density Functional Theory

2003

J. Phys. Chem. A

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Seven stable stationary points, corresponding to three pairs of mirror-image conformers and one C s symmetry conformer, have been located on the potential energy surface (PES) of neutral glycine amide at the B3LYP/ 6-311++G** level of theory. Accurate geometric structures, relative stabilities, and harmonic vibrational frequencies have been investigated. More importantly, the intramolecular H-bond formed from the amide to the amine plays a key role in stabilizing the global minimum, as observed in alanine amide and has been discussed qualitatively from the viewpoint of the structures, charge distributions, and vibrational analyses. As an important supplement in property for glycine amide, other property parameters, such as gas-phase basicity (GB), proton affinity (PA), and ionization potential (IP), have been predicted. The Boltzmann equilibrium distributions for the seven conformers have also been discussed qualitatively through the calculations of Gibbs free energy at various temperatures. At room temperature, the equilibrium compositions are mainly composed of conformers I and II exclusively, i.e., about 75.02% and 23.28%, respectively. As a tentative study, the conformational behaviors in aqueous solution have been explored using the Onsager model within the self-consistent reaction field (SCRF) method at the same level employed in the gas phase. Computational results indicate that the global minimum should be conformer I regardless of whether in the gas phase or in aqueous solution, which is different from the previous theoretical reports. Moreover, the consistent results in relative energy using higher-level computations, including the MP2, MP3, MP4SDQ, and CCSD(T) methods employing the Dunning's correlation consistent basis set aug-cc-PVDZ, indicate that the B3LYP/6-311++G** level of theory may be applied to the analogous systems.

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“…In our proposed mechanism (Figure 4), the reaction generates a mono-urea 3 or bis-urea 4, which slowly cyclize to form the nucleophilic 2iminooxazolidines 5 and 6. These intermediates likely exist as a mixture of tautomers and stereoisomers 58 but react further to form macrocycles only in the Z configurations, which allow for a stabilizing intramolecular hydrogen bond in the final product. 59 Macrocycle 1 is produced by the homocoupling of 5, while its isomer 2 results from the addition of 6 to a second equivalent of diisocyanate.…”

Section: Synthesis and Characterizationmentioning

confidence: 99%

High Yielding Flow Synthesis of a Macrocyclic Molecular Hinge

Jones

Cook

Marquez-Gamez

et al. 2021

Preprint

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Many molecular machines are built from modular components with well-defined motile capabilities, such as axles and wheels. Hinges are particularly useful, as they provide the minimum flexibility needed for a simple and pronounced conformational change. Compounds with multiple stable conformers are common, but molecular hinges almost exclusively operate via dihedral rotations rather than truly hinge-like clamping mechanisms. An ideal molecular hinge would better reproduce the behavior of hinged devices, such as gates and tweezers, while remaining soluble, scalable and synthetically versatile. Herein, we describe two isomeric macrocycles with clamp-like open and closed geometries, which crystallize as separate polymorphs but interconvert freely in solution. An unusual one-pot addition cyclization reaction was used to produce the macrocycles on a multigram scale from inexpensive reagents, without supramolecular templating or high-dilution conditions. Using mechanistic information from NMR kinetic studies and at-line mass spectrometry, we developed a semi-continuous flow synthesis with maximum conversions of 85-93% and over 80% selectivity for a single isomer. The macrocycles feature voids that are sterically protected from guests, including reactive species such as fluoride ions, and could therefore serve as chemically inert hinges for adaptive supramolecular receptors and flexible porous materials.

show abstract

Ab initio and DFT study of molecular structure and tautomerism of 2-amino-2-imidazoline, 2-amino-2-oxazoline and 2-amino-2-thiazoline

Cited by 34 publications

References 25 publications

High-Yielding Flow Synthesis of a Macrocyclic Molecular Hinge

High-Yielding Flow Synthesis of a Macrocyclic Molecular Hinge

Conformational Study of Glycine Amide Using Density Functional Theory

High Yielding Flow Synthesis of a Macrocyclic Molecular Hinge

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