Conformational analysis and selective hydrolysis of 2,5-disubstituted-1,3-dioxane-2-carboxylic acid esters

5-Alkyl-2-methyl-2-carbomethoxy-1,3-dioxanes were found to have a cis preferential configuration in the equilibrium state, and the ester hydrolysis rate of the trans-isomers was faster than that of the cis-isomers. Conformational analysis and charge calculation of the carbomethoxy group in both dioxanes elucidated this selectivity.     

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.     

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 1,3,2-dioxathiane and its oxides

Computer simulation of the routes of conformational isomerization of 1,3,2-dioxathiane and its Soxides by nonempirical quantum-chemical method RHF/6-31G(d) revealed the main and local minima and transition states of this process. It was shown that the barrier of ring inversion is reduced in going from 1,3,2-dioxathiane to its oxides. The established ΔG ⁰ (300 K) value of S=O group in cyclic sulfite (−15.0 kJ mol⁻¹) is in good agreement with the experimental data.     

Conformational analysis—CXXIII: Carboxylic acids and esters in force field calculations

Force field calculations have been extended to include carboxylic acids and esters. Necessary parameters were chosen mainly by fitting to available experimental data on small molecules. A few key facts are not known experimentally, and these were found by carrying out ab initio (STO-3G) calculations. Other molecules were then studied and structural predictions were made. It is predicted that in isobutyric acid a methyl group is twisted 15° from eclipsing the carbonyl oxygen in the ground state. The relative energies and torsional functions for cyclohexanecarboxylic acid are reported. Except for rather simple compounds, such as normal chains, the carboxyl is usually twisted with respect to the attached chain. Some conformations of lactones were also examined. For δ-valerolactone it is predicted that the boat conformation is more stable than the chair. Heats of formation of the compounds can be calculated with fair accuracy.     

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.     

Infrared spectra of heptafluorobutyric acid and some of its esters

Infrared spectra obtained for seven alkyl esters of heptafluorobutyric acid show that 18 vibrations of the CF₃CF₂CF₂CO₂ group have characteristic frequencies in these esters, with most having average deviations of only about 1 cm^?1. The relative intensities of the bands are also quite constant. The infrared spectrum obtained for heptafluorobutyric acid indicates that the acid is completely associated in the neat liquid.     

Reactions of 1,1-dialkylthiosemicarbazides with propiolic acid and its esters

The betaines 2-amino-4,4-dimethyl-²-1,3,4-thiadiazolin-4-io-5-acetates are formed in the reaction of 1,1-dimethylthiosemicarbazides with propiolic acid. 2-Amino-4,4-disubstituted-5-carboalkoxy-methyl-²-1,3,4-thiadiazolinium chlorides, the structure of which has been confirmed by X-ray crystallography, are formed by the reaction of 1,1-disubstituted thiosemicarbazides lower alkyl propiolates in the presence of hydrochloric acid.Translated from Khimiya Geterotsiklicheskikh Soedenenii, No. 12, pp. 1674–1679, 1992.     

Design, synthesis and in vitro evaluation of L-amino acid esters prodrugs of acyclic nucleoside phosphonates as anti-HBV agent

A series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates was synthesized and their anti-HBVactivity was evaluated in HepG2 2.2.15 cells. Compound 1d exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with EC50 and CC50 values of 0.207 mmol/L and 2530 mmol/L, respectively.     

Reaction of amino thiols with chloroacetic acid and its esters

The reaction of amino thiols with chloroacetic acid esters leads to the formation of amino mercapto esters, whereas 6-alkyl(alkoxy)-N-aryltetrahydro-1,4-thiazine-3-ones are formed in the reaction with chloroacetic acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 327–329, March, 1984.     

Conformational analysis: crystallographic,NMR, and molecular mechanics studies of flexible sulfonic esters

Two novel X-ray structures of the sulfonic ester derivatives 2-(6-iodo-1,3-benzodioxol-5-yl)ethyl 4-nitrobenzenesulfonate, 3, and 2-(6-iodo-1,3-benzodioxol-5-yl)ethyl 4-methylbenzenesulfonate, 4, have been obtained in a study aimed at analyzing the structures and conformations of sulfonic ester derivatives that are routinely used in alkaloid syntheses. The crystal structure of 4 is highly unusual, containing four independent molecules that belong to two distinct conformational types: (1) a hairpin conformation (stabilized mainly by intramolecular pi-stacking) and (2) a stepped conformation (stabilized mainly by intermolecular pi-stacking). Compound 3, on the other hand, crystallizes exclusively as the hairpin conformer. New MM+ force field parameters for sulfonic esters have been developed using the X-ray data, empirical rules, and DFT calculations to estimate the bond dipole parameters. Grid searches of conformational space for 3 and 4 using MM methods show that there are several gas-phase conformations within 5 kcal/mol of the global minimum and that the lowest energy conformations (by approximately 4.6 kcal/mol) are of the hairpin type. Analysis of the MM conformational energies suggests that the dominant intramolecular interaction stabilizing the hairpin conformations of 3 and 4 is van der Waals attraction. Moreover, the lattice energies for packing the hairpin conformations of 3 and 4 are approximately 4 kcal/mol more favorable than for the stepped conformations. Various intermolecular interactions contribute to the complexity of the observed crystal structures of 3 and 4, including electrostatic attraction between O and I atoms in neighboring molecules. Langevin dynamics (LD) simulations at several temperatures (6.0 ns, friction coefficient = 2.5 ps(-1)) indicate that the conformational exchange rates are approximately 10(10)-10(11) s(-1) over the temperature range 213-400 K, accounting for the temperature-independent (1)H NMR spectra of 3 and 4.     

Conformational analysis of asymmetric ethanes : Extraction of acyclic conformational ligand constants from time-averaged geminal fluorine anisochronism

The syntheses and ambient-temperature ¹⁹F NMR data are reported for 27 asymmetric ethanes of the general formula RCF₂CXYZ, including a complete series of 10 compounds with R = Cl and all combinations of the 5 ligands H, F, Cl, Br and Ph. Within the theoretical framework of a previously proposed heuristic mathematical model the geminal ¹⁹F chemical shift differences are fitted to chirality functions X = ?R (λx - λy) (λy - λz) (λz - λx) to yield acyclic conformational ligand constants λ and substituent parameters ?. It is demonstrated that the λ constants already reported for an analogous series of 10 compounds with R = Br are transferable to the Cl series with ?_Cl = 0.63 ± 0.07. Crude first approximations are also reported for the normalised (according to ?_Br = 1) ligand constants λ_Ch3, λ_OH, λ_OCH3 and λ₁ and for the substituent parameter λ_H. It is argued that the λ values thus ext play a role in the conformational analysis of asymmetric ethanes that is conceptually analogous to the conformational free energies in monosubstituted cyclohexanes.     

Conformational structure of esters of fluorinated acylpyruvic acids

Esters of fluorinated acylpyruvic acids were obtained for the first time. PMR and IR spectroscopy, dipole moment measurements, and quantum chemical calculations showed that these compounds exist as equilibrium mixtures of E and Z enolic isomers.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1410–1414, June, 1990.