Nitrogen Inversion Barriers Research Articles

The interrelation between the structural, electronic and energy parameters of nitrogen inversion in ammonia derivatives

The structural, electronic and energy parameters in the ground and transition states of inversion of the amines H2NXHn (XHn=CH3, NH2, OH, F, SiH3, PH2, SH, and Cl) have been calculated by using DFT (PBE96/def2-tzvpp) method. It was established that the increase of electronegativity of the substituents (the X atoms within the same period) leads to stabilization of the ground and transition states of the molecules. The increase in the inversion barriers is due to relative stabilization of the ground states, but not due to relative destabilization of the transition states. The inversion barriers rise with a decrease in conformational energies of the substituents, sums of valence angles at the nitrogen atoms, negative charges on them, energies of the nitrogen lone pairs and with an increase in s-character and population of the nitrogen lone pairs and difference between the energies of the nitrogen lone pairs in the ground and transition states. The main parameters that allow predicting the change of the nitrogen inversion barriers, independently of the type or volume of the XHn substituent, are s-character of the nitrogen lone pairs and difference between the energies of the nitrogen lone pairs. In all other cases, the correlations were found only for the amines containing the elements of the same period at the nitrogen atom. All structural and electronic parameters of amines containing the Х atoms from the second period are more sensitive to the changes of the ХНn substituents than the parameters of amines containing the Х atoms from the third period.

N-derivatives of formaldimines: the reason for the high nitrogen inversion barriers in N-methyl- and N-chloroimines

The energy and electronic parameters of the nitrogen inversion in imines Н 2 С=NХН n (ХН n = СН 3 , NH 2 , OH, F, SiH 3 , PH 2 , SH, Cl) have been calculated with the DFT method (B3LYP 6-311+G(d,p)) in terms of natural bond orbital. It has been established that the interactions of the nitrogen lone pair (LP) with the bond orbitals at the imino carbon atom are practically independent of the X atom and contribute to the decrease of the inversion barriers (Δ Е і ≠ ). While nN®σ * X–H , nN«σ X–H and nN«nX interactions substantially depend on the heteroatom type and promote the increase in the Δ Е і ≠ values with the rise in electronegativity of the X atom. The contribution of the interactions of the nitrogen LP with the Rydberg orbitals of the C=N–X group atoms is small and they cannot be the main reason of the decrease in the Δ Е і ≠ values when X atoms of the second period are replaced by atoms of the third period of the same group. The interactions of the LP of the X atoms and the X–H bond orbitals with the C=N bond orbitals have the main influence on the inversion barriers. The contribution of nX®π * C=N interactions to the Δ Е і ≠ values is dominant. The main reason of the “anomalous” inversion barriers of N-methyl- and N-chloroformaldimines is the destabilization of inversion transition states because of the reduction in the energies of σ X–H ®π * C=N and nX→π * C=N interactions and the rise in the energies of nN«nСl interactions. The contributions of electronegativity of ХН n substituents and energies of intramolecular interactions to the Δ Е і ≠ values have been determined.

Mixed dysprosium-lanthanide nitride clusterfullerenes DyM2N@C80-Ih and Dy2MN@C80-Ih (M = Gd, Er, Tm, and Lu): synthesis, molecular structure, and quantum motion of the endohedral nitrogen atom.

Systematic exploration of the synthesis of mixed-metal Dy-M nitride clusterfullerenes (NCFs, M = Gd, Er, Tm, Lu) is performed, and the impact of the second metal on the relative yield is evaluated. We demonstrate that the ionic radius of the metal appears to be the main factor allowing explanation of the relative yields in Dy-M mixed-metal systems with M = Sc, Lu, Er, and Gd. At the same time, Dy-Tm NCFs show anomalously low yields, which is not consistent with the relatively small ionic radius of Tm3+ but can be explained by the high third ionization potential of Tm. Complete separation of Dy-Gd and Dy-Er, as well as partial separation of Dy-Lu M3N@C80 nitride clusterfullerenes, is accomplished by recycling HPLC. The molecular structures of DyGd2N@C80 and DyEr2N@C80 are analyzed by means of single-crystal X-ray diffraction. A remarkable ordering of mixed-metal nitride clusters is found despite similar size and electronic properties of the metals. Possible pyramidalization of the nitride clusters in these and other nitride clusterfullerenes is critically analyzed with the help of DFT calculations and reconstruction of the nitrogen inversion barrier in M3N@C80 molecules is performed. Although a double-well potential with a pyramidal cluster structure is found to be common for most of them, the small size of the inversion barrier often leads to an apparent planar structure of the cluster. This situation is found for those M3N@C80 molecules in which the energy of the lowest vibrational level exceeds that of the inversion barrier, including Dy3N@C80 and DyEr2N@C80. The genuine pyramidal structure can be observed by X-ray diffraction only when the lowest vibrational level is below the inversion barrier, such as those found in Gd3N@C80 and DyGd2N@C80. The quantum nature of molecular vibrations becomes especially apparent when the size of the inversion barrier is comparable to the energy of the lowest vibrational levels.

Six‐Membered Cyclic Nitroso Acetals: Synthesis and Studies of the Nitrogen Inversion Process of N‐Silyloxy‐3,6‐dihydro‐2H‐1,2‐oxazines

Silyl nitronates undergo rhodium‐catalyzed formal [3+3]‐cycloaddition with enol diazoacetates to form N‐silyloxy‐3,6‐dihydro‐2H‐1,2‐oxazines. The scope of the reaction and the extent of the major side process were evaluated. A mechanistic scheme was proposed. The nitrogen inversion barrier in the obtained nitroso acetals was estimated based on both quantum calculations and kinetic measurements.

Nitrogen Stereodynamics and Complexation Phenomena as Key Factors in the Deprotonative Dynamic Resolution of Alkylideneaziridines: A Spectroscopic and Computational Study

The present work is aimed at shedding light on the origin of the stereoselectivity observed in the reactions of chiral heterosubstituted organolithiums, generated by lithiation of alkylideneaziridines. Factors such as the nitrogen inversion barrier, the stereochemistry at the nitrogen atom, the substitution pattern of the alkylideneaziridines, and the reaction conditions are taken into consideration. The interplay between nitrogen stereodynamics and complexation phenomena seems to be crucial in determining the stereochemical outcome of the lithiation/trapping sequence. The findings were rationalized by a synergistic use of NMR experiments, run on the lithiated intermediates, alongside computational data. It has been demonstrated that, in such systems, the stereochemistry-determining step is the deprotonation reaction, and a model based on a deprotonative dynamic resolution has been proposed. Such findings could find application in dynamic systems other than aziridines.

Chiral 1,2-dialkenyl diaziridines: synthesis, enantioselective separation, and nitrogen inversion barriers.

trans-1,2-Disubstituted diaziridines form stable enantiomers at ambient conditions because of the two stereogenic pyramidal nitrogen atoms. Functionalized trans-1,2-disubstituted diaziridines can be utilized as a chiral switching moiety between two enantiomeric states in more complex molecular structures. However, the synthesis of functionalized diaziridines is quite challenging, because of the limited tolerance of reaction conditions that can be applied. Here we present a strategy to make trans-1,2-disubstituted diaziridines accessible as versatile building blocks in C-C-bond formations, i.e., the Heck reaction, and therefore introducing aryl substituents. The synthesis of trans-1,2-dialkenyl diaziridines with terminal alkenyl substituents and their stereodynamic properties are described.

Light-driven molecular motors: imines as four-step or two-step unidirectional rotors.

Chiral N-alkyl imines undergo unidirectional rotation induced by light and heat, thus providing a new class of molecular motors. Depending on the conformational flexibility of the stator part (the carbonyl residue) and the nitrogen inversion barrier of the rotor part (the amine residue) in the molecule, the operation mode of the motor can be controlled as either a four- or a two-step cycling motion of the rotor part.

Stereoselective Amine Addition to Six‐Membered Cyclic Nitronates Promoted by Silyl Triflate

AbstractSix‐membered cyclic nitronates couple with amines or their N‐silyl derivatives in a diastereoselective fashion to give 3‐amino‐substituted nitroso acetals in 53–89 % yield through silyl triflate electrophilic catalysis. Stereodifferentiation of this process is determined by thermodynamic control, which is realized due to reversibility of amine addition and a decreased nitrogen inversion barrier in the resulting nitroso acetals. Selected chemical transformations of nitroso acetals were examined.

Nitrogen Inversion Barriers Affect the N‐Oxidation of Tertiary Alkylamines by Cytochromes P450

Calculations: Cytochrome P450 enzymes facilitate a number of chemically different reactions. For example, amines can be either N-dealkylated or N-oxidized, but it is complex to rationalize which of these competing reactions occurs. It is shown that the barrier for inversion of the alkylamine nitrogen atom seems to be of vital importance for the amount of N-oxidized product formed relative to dealkylation and hydroxylation products.

Nitrogen Inversion Barriers Affect the N‐Oxidation of Tertiary Alkylamines by Cytochromes P450

Nitrogen Inversion Barriers Affect the N‐Oxidation of Tertiary Alkylamines by Cytochromes P450

Nitrogen Dynamics and Reactivity of Chiral Aziridines: Generation of Configurationally Stable Aziridinyllithium Compounds

Diastereomeric oxazolinylaziridines (R,R)-9 and (R,S)-9 have been regioselectively lithiated at the α-position with respect to the oxazolinyl ring. The resulting aziridinyllithium compounds proved to be chemically and configurationally stable under the experimental conditions used, thus furnishing, upon trapping with electrophiles, chiral 2,2-disubstituted aziridines, in contrast to the corresponding α-lithiated oxazolinyloxiranes that have been reported to be chemically stable but configurationally unstable. This peculiar behavior of the nitrogen-bearing heterocycle has been rationalized on the basis of DFT calculations and the observed dynamics of the aziridine nitrogen atom. The DFT analysis allowed the disclosure of a solvent-dependent differing stability of diastereomeric lithiated aziridines (R,R)-9-Li and (R,S)-9-Li, suggesting η(3)-coordinated oxazolinylaziridinyllithium compounds as likely intermediates. Such intermediates could be the result of a dynamically controlled lithiation that relies on the preliminary formation of a complex between the lithiating agent and the oxazolinyl ring. According to this model, the competing complexation of the lithiating agent by the lone pair of electrons on the aziridine nitrogen would cause addition to the oxazoline C=N bond, thus ending up with the formation of oxazolidines, which are precursors of useful chiral ketoaziridines. The proposed model has been also supported by estimating the nitrogen inversion barrier by dynamic NMR spectroscopic experiments.

ChemInform Abstract: Electronic Control of Stereoselectivity in the Chlorination of 1,4- Dihydro-1,4-iminonaphthalenes (7-Azabenzonorbornadienes) with N- Chlorosuccinimide.

Abstract Chlorination of a range of secondary amines based on the 1,4-dihydro-1,4-iminonaphthalene (7-azabenzonorbornadiene) ring system is described. At low temperatures, the ratio of syn- and anti- N-chloroamines formed under conditions of kinetic control can be determined; this ratio is shown to be influenced substantially by variation in the electronic character of the aryl ring. At higher temperatures, inversion at nitrogen leads to different (thermodynamic) invertomer ratios which also vary as a function of substitution. Substituents in the aryl ring and in the bicyclic skeleton also influence the nitrogen inversion barrier.

Conformational analysis and inversion process in some perhydrodipyrido[1,2‐b;1′2′‐e]‐1,4,2,5‐ dioxadiazines

AbstractThe stereoselectivity in the cyclodimerization of several six‐membered cyclic nitrones has been investigated. The configurational/conformational analysis of the dimers (i.e. perhydrodipyrido[1,2‐b;1′2′‐e]‐1,4,2,5‐dioxadiazines) has been carried out by NMR spectroscopy. The NMR spectra of the dimers at lower temperatures indicated the presence of either a single or two invertomer(s). The nitrogen inversion barriers are determined using complete line–shape analysis. The invertomer ratios have been used to estimate the relative energies associated with the cis and trans ring fusion in these tricycles. A mechanistic rationale for the observed stereochemistry of the dimerization process has been presented. Copyright © 2009 John Wiley & Sons, Ltd.

The effect of spiroadamantane substitution on the conformational preferences of N-Me pyrrolidine and N-Me piperidine: a description based on dynamic NMR spectroscopy and ab initio correlated calculations

Dynamic NMR spectroscopy and ab initio correlated calculations revealed that the attachment of a spiroadamantane entity at the C-2 position of N-methylpyrrolidine or N-methylpiperidine induces a severe steric crowding around nitrogen, which changes the conformational space of the heterocycle resulting in: (a) the complete destabilization of the N-Me(eq) conformer in spiranic structures; in contrast the N-Me(eq) conformer corresponds to the global minimum in N-methylpyrrolidine or N-methylpiperidine. The spiroadamantane structure raises the energy of the equatorial conformer because of the severe van der Waals repulsion between the N-Me(eq) group and adamantane C–H bonds. (b) The interconversion between the only populated enantiomeric N-Me(ax) conformers ax→[eq]→ax′; the interconversion eq→ax between N-Me(eq) and N-Me(ax) conformers, which are both populated, is observed in N-methylpyrrolidine or N-methylpiperidine. (c) The raising of ring and nitrogen inversion barriers ax→ts by ∼4–6 kcal mol −1. The dynamic NMR study provides evidence that the most important process required for the enantiomerization between the axial N-Me conformers in spiropiperidine 4 and spiropyrrolidine 5 are different, i.e., a nitrogen inversion in 5 (9.10 kcal mol −1) and a ring inversion in 4 (15.2 kcal mol −1). While an enantiomerization interconverts N-Me axial conformers in spiropiperidine 5 and spiropyrrolidine 4, substitution of the pyrrolidine ring of 5 with a C-Me group effects a diastereomerization between two N-Me axial conformers and reduces effectively the nitrogen inversion barrier according to the protonation experiments and the calculations. In general, all the calculations levels used, i.e., the MM3, B3LYP/6-31+G ∗∗ and MP2/6-311++G ∗∗//B3LYP/6-31+G ∗∗, predict correctly the different stability of the local minima; however only MP2/6-311++G ∗∗//B3LYP/6-31+G ∗∗ was found to be reliable for the calculation of the nitrogen inversion barriers.

A study of conformational behaviour in some hexahydro-2H-isoxazolo[2,3-a]pyridines

A study of the effects of substituents on the conformational behaviour of a series of hexahydro- 2H-isoxazolo(2,3-a)pyridines (a 6/5 fused ring system), prepared via nitrone cycloaddition reaction of 4-butyloxycarbonyl-3,4,5,6-tetrahydropyridine-1-oxide with mono- and disubstituted alkenes, has been carried out. Some of these bicyclic cycloaddition products show the presence of two isomers (cis-and trans-fused system), equilibrating via relatively slow nitrogen inversion process, while the rest exist solely as the trans-invertomer. Stereochemistry of the ring fusion was determined by NMR spectral analyses. The effect of substituents and solvents - CDCl3 toluene-d6, and CD3OD - on the population ratio of the invertomers and inversion barriers has been investigated. The nitrogen inversion barriers, determined using complete line-shape analysis, are in the range 62.1-72.3 kJ mol -1 .

Synthesis and stereochemical analysis of some norephedrine‐derived isoxazolidines

AbstractThe diastereoselectivity in the cycloaddition reactions of several mono‐ and disubstituted alkenes with a (‐)norephedrine‐derived methylenenitrone has been investigated. The stereochemical analysis of the addition products (i.e., isoxazolidines) has been carried out by X‐ray, NMR, and chemical conversions. The NMR spectra of the isoxazolidines at low temperatures indicated the presence of either a single or a predominant invertomer. The stereochemistry of the invertomers and nitrogen inversion barriers are determined using complete line‐shape analysis and their dependence on solvent is discussed. Copyright © 2008 John Wiley & Sons, Ltd.

Study of inversion isomerism in some 4,5- cis-substituted-2-isoxazolidineethanols by NMR spectroscopy

A series of β-phenyl-2-isoxazolidineethanols having cis-disposed substituents at C(4) and C(5) has been prepared by asymmetric nitrone cycloaddition reactions and their NMR spectra recorded over a wide range of temperatures. The spectra in CDCl 3 at low temperatures indicate the presence of two interconverting invertomers for some of the tri-substituted isoxazolidines. The effect of H-bonding – intramolecular in CDCl 3 and intermolecular in CD 3OD – on the population ratio of the nitrogen invertomers has been investigated. The nitrogen inversion barriers are determined using complete line-shape analysis, and their dependence on solvent is discussed.

Conformational analysis, NMR properties and nitrogen inversion of N-substituted 1,3-oxazines

The conformational preference of a set of selected N-substituted oxazines has been investigated at the MP2/6-311+G(d,p) and B3LYP/6-311+G(d,p) levels of theory. From the ΔG0 calculated values, it can be concluded that when the substituent is methyl, ethyl and propyl the axial conformation is preferred in the gas phase. When the substituent is isopropyl or tert-butyl the equatorial conformer is the most abundant in the gas phase. This situation does not change in solution provided the solvent has very low polarity as Cl4C, in good agreement with the experimental findings. However, when the polarity of the solvent increases, the stabilization of the equatorial conformer is quite significant, due to its large dipole moment, and it becomes the dominant form in CHCl3 and CH2Cl2solvents. Quite importantly, the percentage of axial conformer obtained from the values of the 1H chemical shift are in good agreement with the percentage obtained from the calculated free energy. The nitrogen inversion barrier of N-substituted 1,3-oxazines decreases with the size of the substituent. The largest substituent stabilizes the nitrogen lone-pair to the greatest extent in the transition state and is the one that least interacts with the ring when it becomes planar.

2-Isoxazolidineethanols: An NMR study of the effect of intramolecular H-bonding on the population of nitrogen invertomers and inversion process

A series of ( βR, 5R)- and ( βR, 5S)-2,5-disubstituted isoxazolidines: 5-(substituent)-β-phenyl-2-isoxazolidineethanols, have been prepared by asymmetric nitrone cycloaddition reactions and their NMR spectra recorded over a wide range of temperatures. The spectra at low temperatures indicate the presence of the ( βR, 5S) diasteromer almost exclusively as a single invertomer having trans disposition of the substituents at N(2) and C(5), while the ( βR, 5R) diasteromer remained as a mixture of two interconverting invertomers in deuterated chloroform. The effect of H-bonding – intramolecular in CDCl 3 and intermolecular in CD 3OD – on the population ratio of the invertomers and nitrogen inversion process has been investigated. The nitrogen inversion barriers are determined using complete line-shape analysis, and their dependence on solvent is discussed. Due to steric factor the trans-invertomers are found to be more stable than their cis counterparts.

Computational Study of Urea and Its Homologue Glycinamide: Conformations, Rotational Barriers, and Relative Interactions with Sodium Chloride

Conformational behaviors of urea and glycinamide have been investigated using the B3LYP functional with the 6-311+G* and 6-311+G** basis sets. Urea monomers have nonplanar minima at all the levels studied, even in the aqueous phase. In the case of glycinamide, the intramolecular hydrogen bond formed from the amide to the amine is important for stabilizing the global minimum. Bond rotations and nitrogen inversion barriers for glycinamide conformations have also been reported. The DFT calculated results suggest that urea conformers interact preferentially with the {111} surface of sodium chloride and such interactions can be responsible for the change in the habit of sodium chloride. Glycinamide conformers have a lower affinity toward the {111} surface of sodium chloride in water. The pyramidality of nitrogens in urea conformers does not influence the relative trends of interaction energies with sodium chloride surfaces. The mode of interactions predicted at the LDA/PWC/DND level for urea and glycinamide with sodium chloride for both slab and cluster models shows that the amide functionality (-CONH2) interacts with both Na(+) and Cl(-) ions on the {100} surface; however, the carbonyl oxygen of these additives predominantly interacts with the sodium ions on the {111} surface.