Conjugation and hyperconjugation in conformational analysis of cyclohexene derivatives containing an exocyclic double bond

The equilibrium geometry, ring-inversion pathway barriers for analogues of cyclohexene with an exocyclic double bond have been studied using the MP2/6-311 G(d,p) level of theory. The equilibrium conformation of the ring depends on conjugation between the endocyclic and exocyclic double bonds. Interactions between conjugated double bonds include the pi-pi conjugation and interactions between the lone pair of the heteroatom of the exocyclic double bond and the sigma-antibonding orbital of the endocyclic single bond. In the case of the tetrahydrocycles with double bonds separated by a methylene group the balance between the pi --> sigma* hyperconjugation interactions between the exocyclic double bond and the neighboring methylene group and the n --> sigma* interaction between the lone pair of the heteroatom and the sigma-antibonding orbitals of the C(sp(2))-C(sp(3)) bond determine the geometrical parameters of the ring. The character of the potential-energy surface around the saddle point depends on the position of the exocyclic double bond and the orientation of the hydrogen atom attached to the heteroatom of the V group of the periodic table in the tetrahydrocycles with double bonds separated by a methylene group.     

Multistep conformational interconversion mechanism of cyclododecane. A simple and fast analysis using potential energy curves

An ab initio and Density Functional Theory (DFT) study of the conformational properties of cyclododecane was carried out. The energetically preferred equilibrium structures, their relative stability, and some of the transition state (TS) structures involved in the conformational interconversion pathways were analyzed from RHF/6‐31G(d), B3LYP/6‐31G(d,p) and B3LYP/6311++G(d,p) calculations. Aug‐cc‐pVDZ//B3LYP/6311++G(d,p) single point calculations predict that the multistep conformational interconversion mechanism requires 11.07 kcal/mol, which is in agreement with the available experimental data. These results allow us to form a concise idea about the internal intricacies of the preferred forms of cyclododecane, describing the conformations as well as the conformational interconversion processes in the conformational potential energy hypersurface. Our results indicated that performing an exhaustive analysis of the potential energy curves connecting the most representative conformations is a valid alternate tool to determine the principal conformational interconversion paths for cyclododecane. This methodology represents a satisfactory first approximation for the conformational analysis of medium‐ and large‐size flexible cyclic compounds. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012     

Strain energy minimization study of the mechanism of,and the barrier to,conformational interconversion in five-membered diamine chelate rings

The method of Lagrangian multipliers is used to constrain torsion angles during molecular mechanics refinement for the purpose of plotting strain energy against a reaction coordinate. A complete two-dimensional analysis of the conformational interconversion from δ- to λ-[Co(ethane-1,2-diamine) (NH₃)₄]³⁺ reveals a mechanism in which the transition state geometry has an envelope conformation and an inversion barrier of 15.7 kJ mol^?1. Substitution at the carbon atoms, variation of the metal-nitrogen distance, and replacement of the amine ligands with bidentate amines only slightly alters the inversion barrier. Substitution at the nitrogen atoms of the bidentate ligand increases the inversion barrier significantly to 24.6 kJ mol^?1 for (N,N,N′,N′-tetramethylethane-1,2-diamine) [(NH₃)₄]³⁺.     

Eight-membered-ring solid-state conformational interconversion via the atom-flip mechanism, a CPMAS 13C NMR and crystallographic stereochemical study

Nefopam methohalide (chloride, bromide, and iodide) medium-ring quaternary ammonium salts of the non-narcotic analgesic tertiary amine drug give crystals belonging to the identical monoclinic P2(1)/c space group, and all of these pseudopolymorphs exhibit the same packing motif. A singular boat-boat (BB) more compact conformation is observed in the nefopam methochloride crystal. Larger halide anions (bromide and iodide) increase the void distance between the 2(1)-screw axis related adjacent ammonium cations to accommodate void-size dependent equilibrium quantities of the twist-chair-chair (TCC) more extended conformation. The BB:TCC occupancy factors are 0.961(5):0.039(5) [193 K], 0.780(5):0.220(5) [293 K], and 0.755(6):0.245(6) [343 K] for the methobromide crystal, while values of 0.657(5):0.343(5) [193 K] and 0.592(7):0.408(7) [293 K] were measured for the methiodide. Above a minimum of ca. 2.53 A, the occupancy factors were found to be linearly correlated to the intermolecular (TCC)Me(eq)-H...H-Me(ax)(TCC) distance between abutting methyl group protons in 2(1)-screw axis related neighbors. Temperature-dependent occupancy factors for the two conformers are interpreted in terms of a medium ring atom-flip facile interconversion between the two low energy conformations in crystals containing the appropriate size intercation void. A BB/TCC atom-flip interconversion in the methochloride unit cell would result in van der Waals interactions due to an estimated 2.31 A close intermolecular (TCC)Me(eq)-H...H-Me(ax)(TCC) distance between adjacent 2(1)-screw symmetry ammonium cations. The 203 K low-temperature CPMAS 13C NMR spectrum of the methiodide salt showed two slow exchange limit (SEL) delta 57.91 [BB] and delta 63.10 [TCC] OCH2CH2N peaks. A variable low-temperature CPMAS NMR investigation of the solid methiodide showed complex dynamic behavior that cannot be interpreted solely on the basis of an atom-flip conformational interconversion. Local magnetic fields from the gem-dimethyl rapidly rotating proton magnetic dipoles provide a distance-dependent T1 relaxation mechanism for neighboring carbons in the solid-state.     

Synthesis of triaza-2- cyclohexene derivatives

Di- and trialkyl derivatives of 1,3,4-triaza-2-cyclohexene were synthesized by reaction of N,N'-dimethylethyleneaminohydrazine with monocarboxylic acid and their anhydrides, esters, amides, and hydrazides. Alkyl derivatives of ,-bis [2-(1,3,4-triaza-2-cyclohexenyl)]alkanes were obtained as a result of the reaction of N,N'-dimethylethyleneaminohydrazine with dicarboxylic acids and their derivatives. 1-Ammo-1,3,4-triaza-2-cyclohexene derivatives were obtained from ethylenedihydrazine and monocarboxylic acid esters.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 127–129, January, 1977.     

Computer simulation of conformational movement based on interconversion phenomena

A computer method has been developed which is an alternative to molecular dynamics in the sense that it pictures conformational motion. It simulates propagation in conformational movement based on conformational interconversion phenomena. The method starts with the knowledge of the topology of the conformational potential energy hyper-surface, which is described by the minima and the transition states. The topology is obtained by the recently described software . The simulation of conformational motion is based on the Boltzmann statistics of movement between the minima and the transition states at a given temperature. The method is illustrated for methyl--glucopyranoside and - -galNAc(1-3)[- -Fuc(1-2)]Gal-O-Me molecules. Conformational transitions of hydroxyl groups as well as glycosidic linkages are discussed.     

Kinetics and mechanism of the hydrogenation of cyclohexene

The rate of hydrogenation of cyclohexene, catalyzed by CoH₃(PPh₃)₃, has been measured under various conditions and, based on these data, a mechanism has been postulated. For the individual steps of the mechanism enthalpy and entropy differences have been determined. The interpretation of these parameters gives evidence for a more detailed mechanism, in which solvent molecules play an important part as “stand-in” for ligands, dissociated from the catalyst species.     

Infrared-induced conformational interconversion in carboxylic acids isolated in low-temperature rare-gas matrices

An overview of our recent studies dealing with infrared-induced conformational interconversion of carboxylic acids isolated in rare-gas matrices is presented. Extensive rotational photoisomerization studies have been performed on formic acid, which is the simplest organic acid enabling this kind of processes. Formic acid has two conformers and interconversion between them can be induced by vibrational excitation. As such, it is an ideal model system to study the conformational dynamics of the carboxylic group. Formic acid molecules were found to be isolated in different local environments within the rare-gas matrices, as shown by the site splitting of the vibrational bands. Narrowband tunable infrared (IR) radiation was used to induce site-selective isomerization processes. The induced changes in the IR absorption spectra allowed for a detailed analysis of the vibrational properties of both conformers of formic acid isolated in solid argon. In particular, derived from the intermode coupling constants the local environment was shown to affects the intramolecular potential energy surface. Tunneling is involved in the rotamerization of formic acid, with the tunneling rate being affected by the local environment. Additionally, formic acid exhibits isomer-selective photodissociation where narrowband IR excitation can control the conformer-dependent photodissociation channels. Tunable IR radiation was also used to promote rotamerization in a series of matrix-isolated dicarboxylic acids (ethanedioic, propanedioic, and 2-butenedioic acids) by exciting the first overtone of the OH stretching mode or a suitable combination mode at similar energies. Efficient isomerization involving rotation around the CO bond was observed in most cases whereas the internal rotation around the CC bond was found to be constrained for ethanedioic and (Z)-2-butenedioic acids.     

Synthesis of bisalkylthio derivatives of cyclopentene and cyclohexene

Conclusions Alkyl mercaptans react with-chlorocyclopentanone and-chlorocyclohexanone to give the corresponding 1,2-bisalkylthiocyclenes.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1161–1162, May, 1984.     

The synthesis and properties of some mesomorphic cyclohexene derivatives

This paper describes the synthesis and mesomorphic properties of some new liquid crystalline cyclohexene derivatives.     

Synthesis and inhibition properties of conformational probes for the mutase-catalyzed UDP-galactopyranose/furanose interconversion

UDP-galactose mutase is a flavoenzyme that catalyzes the isomerization of UDP-galactopyranose into UDP-galactofuranose, a key step in the biosynthesis of important bacterial oligosaccharides. Several mechanisms for this unique ring-contraction have been proposed, one of them involving a putative 1,4-anhydrogalactopyranose as an intermediate in the reaction. The purpose of this study was to probe the mutase binding site with conformationally restricted analogues of its substrate. Thus, we describe the straightforward synthesis of two C-glycosidic UDP-galactose derivatives: analogue 1, presenting a galactose moiety locked in a bicyclic (1,4)B boat conformation, and UDP-C-Galf 2, where the galactose residue is locked in the conformation of the mutase substrate. The two molecules were found to be inhibitors of UDP-galactose mutase at levels depending on the redox state of the enzyme. Strong inhibition of the native enzyme, but a low one of the reduced mutase, were observed with UDP-C-Galf 2, whereas 1 displayed intermediate inhibition levels under both native and reducing conditions. These data provide evidence of a significant conformational difference of the mutase binding pocket in the reduced enzyme and in the native one, the enzyme switching from a low Galf-affinity state (reduced enzyme) to a very strong one (native enzyme). It is remarkable that the mutase binds the boat-locked analogue 1 with similar affinities in both its conformational states. These results support a mechanism involving the formation of 1,4-anhydrogalactopyranose as a low-energy intermediate. An alternative explanation would be that the distortion of the galactose moiety during the cycle contraction transiently brings the carbohydrate into a conformation close to a (1,4)B boat.     

On the mechanism of liquid phase halogenation of adamantane derivatives

The novel mechanistic representation of adamantane derivatives halogenation process is introduced.     

Organocatalytic domino reactions: synthesis of densely functionalized cyclohexene derivatives

A highly enantioselective domino reaction of α,β-unsaturated aldehydes and 4-acetyl-5-oxohexanal catalyzed by a chiral secondary amine catalyst has been developed, providing an efficient synthetic approach for the synthesis of densely functionalized chiral cyclohexene derivatives with high yields (up to 96%) and enantioselectivities (up to 97% ee) under mild conditions.     

Formation of dihydroperoxide derivatives during the oxidation of cyclohexene and tetralin by dioxygen

¹H- and¹³C-NMR investigations revealed that prolonged oxidation of unsubstituted cyclohexene and tetralin, containing symmetrical and weak allylic and benzylic CH bonds, results in the formation of both mono- and dihydroperoxo derivatives.     

Multistep mechanism of conformational transitions in metallatranes

The results of an investigation of the spin-spin coupling constants of the protons in the OCH₂CH₂N fragments of asymmetric derivatives of metallatranes and the two-dimensional ¹H NMR (NOESY) spectra of 1-substituted 3,6,10-trimethylsilatranes provide evidence in support of a multistep exchange mechanism for conformational transitions, rather than the synchronous conversion of metallatranes in solution.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 129–133, January, 1987.