Conformational preferences and internal rotation in alkyl- and phenyl-substituted thiourea derivatives

Potential energy surfaces (PES) for rotation about the N-C(sp(3)) or N-C(aryl) bond and energies of stationary points on PES for rotation about the C(sp(2))-N bond are reported for methylthiourea, ethylthiourea, isopropylthiourea, tert-butylthiourea, and phenylurea, using the MP2/aug-cc-pVDZ method. Analysis of alkylthioureas shows that conformations, with alkyl groups cis to the sulfur atom, are more stable (by 0.4-1.5 kcal/mol) than the trans forms. All minima adopt anti configurations with respect to nitrogen pyramidalization, whereas syn configurations are not stationary points on the MP2 potential surface. In contrast, analysis of phenylthiourea reveals that a trans isomer in a syn geometry is the global minimum, whereas a cis isomer in an anti geometry is a local minimum with a relative energy of 2.7 kcal/mol. Rotation about the C(sp(2))-N bond in alkyl and phenyl thioureas is slightly more hindered (9.1-10.2 kcal/mol) than the analogous motion in the unsubstituted molecule (8.6 kcal/mol). The maximum barriers to rotation for the methyl, ethyl, isopropyl, tert-butyl, and phenyl substituents are predicted to be 1.2, 8.9, 8.6, 5.3, and 0.9 kcal/mol, respectively. Corresponding PESs are consistent with the experimental dihedral angle distribution observed in crystal structures. The results of the electronic structure calculations are used to benchmark the performance of the MMFF94 force field. Systematic discrepancies between MMFF94 and MP2 results were improved by modification of selected torsion parameters and one of the van der Waals parameters for sulfur.     

Conformational analysis of 2-oxo-1,2,3,4,-tetrahydropyridine and its alkyl- and phenyl-substituted derivatives

The molecular geometries and inversion barriers of the rings in 2-oxo-1,2,3,4-tetrahydropyridine and its alkyl-substituted (Me, Et, Prⁱ, or Bu^t) and phenyl-substituted derivatives were calculated by the molecular mechanics method. The introduction of substituents has no substantial effect on the equilibrium conformation of the heterocycle (a distorted sofa). For 4-alkyl- and 3-alkyl-substituted derivatives (except for 4-Me and 4-Et derivatives), an axial orientation of the alkyl group is more favorable. The phenyl substituents have equatorial and axial orientations at postions 4 and 3, respectively. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1584–1586, September, 1997.     

Conformational populations and rotational barriers in esters

The $\text{trans}$ conformations of methyl, ethyl and isopropyl formate were shown to be present in equilibrium in a polar solvent with the $\text{cis}$ conformations to significant (> 1% 230 K) but much lower extents than for t-butyl formate; rotational barriers for the former compounds are greaters.     

Mass spectra of some alkyl- and phenyl-substituted thiazoles

The mass spectra of a number of alkyl- and methyl-phenyl-substituted thiazoles at various ionizing electron energies were studied. The predominant disintegration reactions are processes involving contraction of the starting ring to form charged sulfur-containing fragments and nitrogen-containing neutral particles. It was noted that the peaks of the (M-H)⁺and (M-CH₃)⁺ ions are of low intensity, that the probability of rearrangement processes with ring expansion is low, and that the position of the methyl groups has a pronounced effect on the disintegration of the molecules during electron impact.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1372–1377, October, 1971.     

Electronic absorption spectra of alkyl- and phenyl-substituted pyrylium salts

Absorption spectra in the region 220–400 mμ have been determined for alkyl- and phenyl-substituted pyrylium salts. Three bands are apparent, in the decreasing order of wavelength, x, y, and x′ bands. These bands are differently influenced by substitution in and γ positions. Relationships of these bands with transitions in other aromatic compounds are established, and the effect of heteroatom variation in the series III–VI on the spectrum is discussed.     

Synthesis of stereoisomeric alkyl- and phenyl-substituted 5-cyanopiperidine-3,4-diols

-Hydroxy--[N-(2-cyanoethyl)amino]ketones were obtained by the reaction of methyl- and phenyl-substituted 2-acyloxiranes with 3-alkylaminopropionitriles. Treatment of the products with sodium tert-butoxide gave stereoisomeric 5e-cyanopiperidine-3,4-diols, the three-dimensional structures of which were established by means of spectral data, as well as by means of isomerization and oxidation with periodic acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1207–1211, September, 1986.     

Synthesis of alkyl- and phenyl-substituted 4-aminomethyl-2-buten-4-olides

4-Aminomethyl-2-buten-4-olides, 5-hydroxy-5,6-dihydro-2-pyridone, and isomeric 8,9-dihydro-4-cyano-2-oxofuro[2,3-c]piperidines were obtained by the base-catalyzed cyclization of 5-amino-4-hydroxy-4-alkyl-2-pentenoic acid esters. 5-Di-methylamino-3-methyl-4-oxovaleric acid ester and 4-dimethylamino-2-buten-4-olide, respectively, were isolated by isomerization of 5-dimethylamino-3-methyl-4-hydroxy-2-pentenoic acid ester and 4-dimethylamino-2-penten-5-olide in the presence of sodium isopropoxide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1313–1319, October, 1987.     

Conformational analysis of 5,6-dihydropyrimidine and its derivatives

The equilibrium geometry and inversion barriers of 5,6-dihydropyrimidine, 6,7-dihydroazolopyrimidines with node nitrogen atoms and their alkyl (Me, Et, Prⁱ, Bu^t) and phenyl derivatives were calculated using a molecular mechanics approach. Annelation with azole cycles and the introduction of substituents have a slight effect on the equilibrium conformation of the dihydrocycle (distorted sofa). Alkyl substutuents at saturated carbons have an essentially equatorial orientation in 5,6-dihydropyridimine derivatives and are axial in the annelated analogs. On the other hand, the equatorial conformers are more stable in phenyl derivatives of dihydroazolopyrimidines. Factors determining the relative stability of conformers were analyzed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 487–491, March, 1995.     

Conformational analysis of furan and thiophen carbonyl derivatives

The 220 MHz NMR spectra of furan and thiophen carbonyl compounds were measured, and further investigated by benzene solvent shifts, induced chemical shifts by the lanthanide shift reagent Eu(FOD)₃; and by the Nuclear Overhauser effect.Two planar isomers of the furan derivatives exist in the ratio of ca. 1:1·05 ～ 1:1·18 (cis/trans), while the cis form of thiophen derivatives is favoured. Semi-empirical calculations (CNDO/2) are reported and the influence of sulfur 3d-orbitals are discussed.     

Conformational analysis of 3,4-dihydropyridine and its alkyl derivatives

The geometry of dihydropyridine and its alkyl derivatives was studied by the molecular mechanics method. The dihydrocycle was found to be mobile; however, substituents exert little effect on its distorted sofa conformation. The alkyl groups attached to the saturated carbon atoms occupy pseudo-equatorial position in monosubstituted and pseudo-axial positions in disubstituted 3,4-dihydropyridines. Unusually high barriers to inversion of the dihydrocycle were observed incis-3,4-dialkyl-3,4-dihydropyridines caused by the eclipse of the substituents in the transition state.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1009–1012, June, 1994.     

Resolution and rotational barriers of quinolinone and acridone sulfenamide derivatives: demonstration of the S-N chiral axis

Achiral (8a) and chiral (8b) N-(2,4-dinitrobenzenesulfenyl)acridone derivatives were synthesized. Addition of the chiral solvating agent (S)- 2,2,2-trifluro-1-(anthryl)ethanol to 8a rendered the enantiotopic groups on the acridone ring diastereotopic and anisochronous, thus allowing the estimation of a lower limit for the rotational barrier about the S-N bond (18.7 kcal mol(-)(1)) by NMR spectroscopy. 8b and the previously reported chiral sulfenamide 5 (Raban, M.; Martin, V. A.; Craine, L. J. Org. Chem. 1990, 55, 4311) were resolved on a Chiracel OD HPLC column. This constitutes the first resolution of stereostable enantiomers of a compound in which the chirality is due only to the presence of the S-N chiral axis. The rotational barriers of both compounds are nearly equal (22.7-22. 8 kcal mol(-)(1) at 303.7 K) and are the largest determined to date for the rotation about the S-N bond in sulfenamides. The relatively high enantiomerization barrier for 8b is remarkable since the peri positions are unsubstituted.     

Conformational analysis,barriers to internal rotation and vibrational assignment for dimethylethylamine

The IR (50–3500 cm^?1) and Raman (20–3500 cm^?1) spectra have been recorded for gaseous and solid dimethylethylamine. Additionally, the Raman spectrum of the liquid has been recorded and qualitative depolarization values have been obtained. Due to the fact that three distinct Raman lines disappear on going from the fluid phases to the solid state, it is concluded that the molecule exists as a mixture of the gauche and trans conformers in the fluid phases with the gauche conformer being more stable and the only one present in the spectra of the unannealed solid. From the temperature study of the Raman spectrum of the liquid a rough estimate of 3.9 kcal mol^?1 has been obtained for ΔH. Relying mainly on group frequencies and relative intensities of the IR and Raman lines, a complete vibrational assignment is proposed for the gauche conformer. The potential functions for the three methyl rotors have been obtained, and the barriers to internal rotation for the two CH₃ rotors attached to the nitrogen atom have been calculated to be 3.51 and 3.43 kcal mol^?1, whereas the barrier for the CH₃ rotor of the ethyl group has been calculated to be 3.71 kcal mol^?1. The asymmetric torsional mode for the gauche conformer has been observed in both the IR and Raman spectra of the gas at 105 cm^?1 with at least one hot band at a lower frequency. Since the corresponding mode has not been observed for the trans conformer, it is not possible to obtain the potential function for the asymmetric rotation although estimates on the magnitudes of some of the terms have been made. Significant changes occur in the low-frequency IR and Raman spectra of the solid with repeated annealing; several possible reasons for these changes are discussed and one possible explanation is that a conformational change is taking place in the solid where the trans form is stabilized by crystal packing forces. These results are compared to the corresponding quantities for some similar amines.     

Conformational analysis of gossypol and its derivatives by molecular mechanics

Conformations and inversion pathways leading to racemization of all the tautomers of gossypol, gossypolone, anhydrogossypol, and a diethylamine Schiff's base of gossypol were investigated with MM3(2000). All forms have hindered rotation because of clashes between the methyl carbon atom and oxygen-containing moieties ortho to the bond linking the two naphthalene rings. Inversion energies generally agree with available experimental data. Gossypol preferentially inverts in its dihemiacetal tautomeric form through the cis pathway (where similar groups clash). Gossypolone inverts more easily than gossypol, and preferentially through the trans pathway (where dissimilar groups clash) when one of its outer rings has an enol-keto group and the other has an aldehyde group. Anhydrogossypol racemizes through the cis pathway. The bridge bond and the ortho exo-cyclic bonds in all the structures bend from planarity, and the inner naphthalene rings pucker to accommodate the inversion. For gossypol, the transition is achieved through greater bending of the exo-cyclic bonds (up to 12°) and less distortion of the inner benzyl rings (q≤0.34 Å), (up to 12.7°) . For gossypolone the transition occurs with greater distortion of the inner benzyl rings (q≤0.63 Å) and less out-of-plane bending (up to 8.4°). By isolating individual clashes, their contribution to the overall barrier can be analyzed, as shown for the dialdehyde tautomer of gossypol.     

Methyl rotational barriers in amides and thioamides

The methyl rotational barriers for a series of N-methyl-substituted amides and thioamides have been calculated at the MP2/6-311+G** level. A comparison of the N-methylformamide and methyl formate barriers indicates that the H [bond] C(Me) [bond] N [bond] H eclipsed torsional arrangement destabilizes an amide by about 0.8 kcal/mol. A comparison of thioamides and amides showed the importance of steric repulsion between the sulfur and a methyl hydrogen in the Z-forms of the thioamides. The C [bond] N bond rotation transition states of the N,N-dimethyl amides have much larger methyl rotational barriers than found in the ground states. They can be attributed to the smaller CH(3)(-)N [bond] CH(3) bond angles in the transition states.     

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.     

Conformational analysis of 2-anthryl-ethylene derivatives: Photochemical and computational investigation

2-Anthrylethylene derivatives 1 E?C5 E and 1 Z are synthesized to study the cis-trans photoisomerization. Interestingly, unlike 9-anthrylethylene derivatives, 2-anthrylethylene derivatives 1 E to 5 E do not exhibit E(trans) to Z (cis) photoisomerization upon direct and triplet sensitization. One-way Z (cis) to E (trans) photoisomerization of 1 Z is found to be very efficient under direct and triplet sensitization conditions, demonstrating the involvement of both singlet and triplet states. 1 E?C5 E exhibits excitation wavelength dependent fluorescence indicating the existence of conformers (rotamers) at room temperature, which is confirmed by fluorescence lifetimes measurements of compounds 1 E and 2 E. Theoretical studies are carried out at DFT and ab initio methodology and the calculated relative energy difference of the conformers is very small; it ranges between 2.9 kJ·mol^?1 to 6.3 kJ·mol^?1 for both ground and excited states.     

Conformational energies and rotational barriers in 3-methyl-1-butene and 1-butene: An ab initio and molecular mechanics study

The calculated result obtained with MM2(87) for the rotation of the isopropyl group in 3-methyl-1-butene is not in agreement with experimental data. In order to reparametrize the C_sp2-C_sp3-C_sp-C_sp3 torsional angle, 3-methyl-1-butene and 1-butene have been studied by molecular mechanics (MM2(87)) and ab initio (MP2/6-31G* and MP3/6-31G*) calculations. The reparametrization of the torsional angle gives calculated results from MM2(87) in agreement with experimental data and ab initio calculations for both 3-methyl-1-butene and 1-butene. The calculated barriers for the rotation of alkyl groups in alkylbenzenes are improved with these new parameters.     

Calculation of rotational barriers in amorphous polymers

The Monte Carlo method was used for generation of amorphous polyethylene configurations on a diamond lattice. Chain building was performed on the tetrahedral lattice of edges 36, 62 and 43 Å with periodic boundary conditions imposed.32 chains were generated, each with a length of 100 CH₂-groups (resulting density = 0.81 g·cm⁻³). Small spherical volumes with a radius of 10 Å were chosen at random from the total volume for the calculation of rotational barriers. The rotating bond was chosen to be close to the center of this sphere. We employed the method of molecular mechanics in order to calculate the rotational barriers. The calculation was made for 578 rotating bonds and the obtained distribution of rotational barriers is approximated by the corresponding Γ-distribution.     

Molecular mechanics calculations of conjugated amides and an ab initio investigation of acrylamide and its β-amino derivative: Conformational analysis and rotational barriers

Conformations and rotational barriers in a series of conjugated primary and tertiary amides have been analyzed by a modified MM2(91) force field, which treats the amide nitrogen as part of the conjugated system by redefining the atom type for the nitrogen. Ab initio molecular orbital calculations at the MP2/6-31G* level have been performed on the stable conformers and transition structures of acrylamide and β-trans-aminoacrylamide. The results have been used, with published experimental and computational data, to generate parameters for the MM2 force field. The force field has been applied to various conjugated amides, such as reduced nicotinamide adenine dinucleotide (NADH) and NAD⁺ analogues, nicotinamide, urea, vinylogous urea derivatives, and nucleic acid bases. The fundamental difference between primary and tertiary conjugated amides with respect to both conformation and barrier is highlighted. © 1996 by John Wiley & Sons, Inc.