Conformational analysis—VIII : 1H NMR conformational study of 5-methyl-, 2,5-dimethyl- and 2,2,5-trimethyl-4-oxo-1,3-dioxans

Substituent effects on ¹H chemical shifts of a large number of methyl-substituted 4-oxo-1,3-dioxans have been estimated and shown to be additive for compounds with a uniform half-chair conformation. The additivity rule fails, however, if the substitution pattern forces the ring into a non half-chair conformation. The ring conformations of 5-methyl-, cis- and trans-2,5-dimethyl- and 2,2,5- trimethyl-4-oxo-1,3-dioxans have been clarified by NMR and through acid-catalyzed equilibration of the epimeric 2,5-dimethyl derivatives.     

Ionisation and appearance potentials in the evaluation of nonbonded interactions—IV: Conformational effects in methyl-substituted 1,3-oxathianes

The ionization and appearance potentials for the molecular and [M ? Me]⁺ ions of several stereoisomeric methyl-1,3-oxathianes were measured. The differences between the ionisation and/or appearance potentials are shown to correlate well with the conformational energy differences in question.     

Properties and reactions of 1,3-oxathianes—II: Mass spectra of 1,3-oxathiane and its alkyl derivatives

The mass spectral fragmentation patterns of 1,3-oxathiane and several of its alkyl derivatives have been recorded. Of the nine possible modes of ring cleavage yielding fragments containing two to four atoms, only six modes were actually observed and, moreover, two of them clearly predominated. The modes of fragmentation of 1,3-oxathianes differ from those of 1,3-dioxanes, but resemble closely those observed for 1,3-oxathiolanes when the different ring sizes are taken into account.     

Conformational thermodynamic and kinetic parameters of methyl-substituted 1,3-butadienes

The s-trans/s-cis conformational equilibria of 10 methyl-substituted 1,3-butadienes [(E)- and (Z)-1,3-pentadiene; 2-methyl-1,3-butadiene; (E)-2-methyl-1,3-pentadiene; 2,3-dimethyl-1,3-butadiene; (E,E)-, (E,Z)-, and (Z,Z)-2,4-hexadiene; 2,5-dimethyl-2,4-hexadiene; and (E,E)-2,4-dimethyl-2,4-hexadiene] were explored by trapping high-temperature conformational equilibria by cryogenic deposition. The vapor state enthalpy differences of these s-trans/s-cis conformers, DeltaH(t equilibrium c), were determined by varying the equilibrating temperature and integrating the resulting matrix isolated IR spectra. The results obtained are in good agreement with ab initio calculations at the G3 level. From these thermodynamic parameters, methyl group nonbonded interactions in conjugated 1,3-butadienes were delineated. Rates of decay of s-cis conformers to their s-trans rotamers were obtained in the solid-state by warming up trapped high-temperature equilibrated samples formed from neat depositions. These data were analyzed in terms of dispersive kinetics with matrix site effects in the solid-state modeled by a Gaussian distribution of activation energies. The activation barriers thus obtained were compared with G3 calculations of the enthalpies of activation.     

Conformational analysis 29: Preparation and1H and13C NMR,FTIR, MS,and crystallographic conformational and configurational study of 3-Oxo-1,3-oxathiane and its monomethyl derivatives

3-Oxo-1,3-oxathiane (1) and its monomethyl derivatives were prepared by oxidation of the corresponding 1,3-oxathianes. The structural analysis was carried out by¹H and¹³C NMR, FTIR, and mass spectrometry. At 298 K compound1 was a 1 1 (at 173 K a 3 1) mixture of the SO(ax) and SO(eq) chair forms. The major oxidation products of methyl 1,3-oxathianes attained exclusively the SO(ax), Me(eq) chair forms except that of the 5-methyl derivative, which consisted of 7% of the SO(eq), Me(ax) chair conformation in CDCl₃ solution. The minor products of oxidation existed in anancomeric SO(eq), Me(eq) chair conformations. The oxidation of 2-methyl- 1,3-oxathiane, however, led to 3,3-dioxo derivative (6) in addition to thetrans [SO(eq)] monoxide. The crystal structures of6 andtrans-3-oxo-5-methyl-1,3-oxathiane were solved by X-ray diffractometry.     

A variable temperature 1H NMR and DFT study of procyanidin B2 conformational interchange

Two procyanidin B2 conformers were identified in a relative abundance ratio of approximately 3:1 at 298 K by ¹H NMR experiments in acetonitrile. The conformational interchange reactions between these two conformers are 1st order in both reactions, with ?G^? for forward and reverse of 57.12?±?5.62 and 54.56?±?5.48 kJ mol^?1, respectively. The experimentally obtained standard thermodynamic energies for this reaction are ΔH⁰_rxn (3.67?±?0.22 kJ mol^?1), ΔS⁰_rxn (4.05?±?1.57 kJ mol^?1 K^?1), and ΔH⁰_rxn (2.96?±?0.33 kJ.mol^?1). Conformational search results at the DFT (PBE, PBE-D2, and B3LYP with 6-311++g**) level of theory yielded four novel conformations, named fully compact (FC), partially compact (PC), partially extended (PE), and fully extended (FE). Although the FC conformer is electronically the most stable of the four as a result of extensive intramolecular non-covalent interactions, the PC and FE conformers are thermodynamically favored in a 5:1 ratio (B3LYP), with the FC and PE conformers present in negligible amounts at equilibrium. The DFT computed standard reaction energies using the B3LYP functional for the PC_major to FE_minor conformational interchange reaction compare exceptionally well with experimental data at 298 K: ?G⁰_rxn (3.86 kJ mol^?1), ΔH⁰_rxn (5.34 kJ mol^?1), and ?S⁰_rxn (4.97 kJ mol^?1 K^?1). It was found that inclusion of solvation energies is crucial to obtain accurate thermodynamic energies. The secondary equilibria found in chromatographic separations are predicted to be highly dependent on solvent polarity and temperature. Similar conformational diversity and hierarchies should exist for all non-rigid procyanidin oligomers and the unique chromatographic behavior of these compounds may be a result of conformational interchange.

     

A NMR investigation of proline and its derivatives. II—Conformational implications of the 1H NMR spectrum of L-proline at different pH

The 250 MHz ¹H NMR spectrum of L -proline is comprehensively analysed by computer simulation for different pH values. A fast endo–exo interconversion has already been proposed from chemical shift and coupling constant data. A critical comparison of the vicinal coupling constants leads to the conclusion that in basic solution the equilibrium is shifted towards a more endo conformation. The position of the carboxylic plane in the ring space is given by the relative intramolecular chemical shift of the geminal protons and by the typical patterns of the H_α multiplet. These results are applied to the analysis of the spectra of Pro? NH₂ and Ac? Pro? NH₂.     

Synthesis and NMR spectroscopic properties of some methyl-substituted 1-methyl-1,4-dihydropyridines

The synthesis and NMR spectroscopic properties of some methyl-substituted 1-methyl-1,4-dihydropyridines are described.     

Conformational analysis: XXI—1H NMR study of 4,5-dimethyl-, 2,4,5-trimethyl- and 2,2,4,5-tetramethyl-1,3-dithiolanes

The 60 MHz ¹H NMR spectra of seven differently substituted 4,5-dimethyl-1,3-dithiolanes have been recorded and analysed. Configurational assignments are made and conformational aspects are discussed in the light of the spectral parameters.     

A theoretical study of conformational properties of N-methyl azapeptide derivatives

The conformational properties of azapeptide derivatives, Ac-azaGly-NHMe (1), Ac-azaAla-NHMe (2), Ac-NMe-azaGly-NHMe (3), Ac-NMe-azaAla-NHMe (4), Ac-azaGly-NMe(2) (5), Ac-azaAla-NMe(2) (6), Ac-NMe-azaGly-NMe(2) (7), and Ac-NMe-azaAla-NMe(2) (8), were systematically examined by using ab initio MO and DFT methods. Structural perturbations in azapeptides resulting from cyclic substitution of a methyl group at three N-positions of an azaamino acid were studied on the basis of the structure of the simplest model azapeptide, 1. Potential energy surfaces were generated at the HF/6-31G level for 1-4 and at the HF/6-31G//HF/3-21G level for 5-8 by rotating two key dihedral angles (phi, psi) in increments of 30 degrees. The backbone (phi, psi) angles of the minima for 1-4 are observed at the i + 2 position to form the betaI(I')-, betaII(II')-, betaVI-turns or the polyproline II structure according to the orientation of the acetyl group and the positions of the N-methyl groups. Compounds 5-8 coupled to a secondary amine were found to preferentially adopt polyproline II, betaI(III)-turn, or alpha-helical structure or even extended conformations depending on the orientation of the acetyl group and the positions of the N-methyl groups. Furthermore, N-methyl groups, depending on their positions, were found to affect the orientation of the amide group in the lowest energy conformations, the pyramidality of the N2 atom, and the bond length in azapeptide derivatives. These unique theoretical conformations of N-methyl azapeptide derivatives could be utilized in the definite design of secondary structure for peptides and proteins, and in the development of new drugs and molecular machines.     

Synthesis and1H NMR study of some organotin derivatives of diethanolamines

A number of organotin derivatives of diethanolamines (stannocanes) R₂Sn(OCH₂CH₂)₂NR', O(SiMe₂CH₂)₂Sn(OCH₂CH₂)₂NR', and Sn[(OCH₂CH₂)₂NR']₂ (R = Ph,cyclo-Hex; R' = H, Me, Ph) were synthesized and studied by¹H NMR spectroscopy. The effect of steric factors on the ability of molecules of stannocanes to form associates in solutions is discussed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp.714–718, April, 1994.     

Configurational and conformational studies of N,N-dimethylpiperidinium derivatives by 13C and 1H NMR spectroscopy

The ¹³C and ¹H NMR spectra of a series of methiodides of mono- and di-C-methyl derivatives of 1-methyl-4-phenyl-4-piperidinols are reported and chemical shift data analysed in terms of configurations and conformations of isomeric sets. Results demondtrate the value of quaternary salt NMR data as an aid to configurational assignment, and the evaluation of non-bonded interactions governing conformational equilibria in piperidine derivatives.     

1H and 13C NMR study of dihydro derivatives of methylphenobarbital

Sodium borohydride reduction of methylphenobarbital leads to the formation of two different dihydroderivatives, reduced either in position 4 or position 6. The structures of the derivatives have been determined through analysis of the ¹H and ¹³C NMR spectra of phenobarbital, methylphenobarbital and their derivatives. Detailed interpretation of the spectra and the resulting spectral parameters indicate conformations where the hydroxyl groups are axial and trans to the ethyl group. In these configurations the phenyl ring becomes equatorial. The results also allow an unambiguous assignment of the resonances of the phenyl carbons 2′(6′) and 3′(5′) of phenobarbital and the carbonyl carbons 4 and 6 of methylphenobarbital, differing interpretations having been previously advanced in the literature.     

NMR experiments on acetals—56 : Conformational study of 1,3-dioxene

From the ¹H-NMR parameters, extracted from the spectra of 1,3-dioxene, 5-Me-1,3-diox-4-ene, 4,5-diMe-1,3-diox-4-ene and of 2,4,5-triMe-1,3-diox-4-ene, it follows that the preferred conformations are the 1,2-diplanar (sofa) C₂ form (Fig. 1B). The barrier to ring reversal in 5-Me-1,3-dioxene was found to be 7·2±0·2 kcal/mole at ?123° (in freon-21).     

Asymmetric reactions based on 1,3-oxathianes3̄: Secondary α-hydroxyacids,RCHOHCO2H and glycols RCHOHCH2OH

Reduction of the previously prepared¹ chiral 2-acyl-l,3-oxathianes derived from (+)-pulegone with various metal hydride combinations proceeds stereoselectively, with diastereomer excess (d.e.) of as much as 97% in the case of reduction of phenyl ketones with lithium tri-sec.butylborohydride. Lesser selectivity (maximum 82% d.e.) is achieved with primary or tertiary alkyl ketones: the predominant diastereomer is readily purified by chromatography. The major product in these cases is that predicted by Cram's chelate rule. The product ratio is reversed with diiasobutylaluminum hydride and also in the reduction of secondary alkyl ketones with lithium sec. butylborohydride, where stereoselectivity is low. The 2-hydroxyalkyl-l,3-oxathianes are cleaved to α-hydroxyaldehydes with N-chlorosuccinimide-silver nitrate and the aldehydes reduced to glycols, RCHOHCH₂OH with sodium borohydride with little or no racemization. Esters, RCHOHCO₂CH₃, are obtained in high enantiomeric purity by O-benzylating the 2-hydroxyalkyl-l,3-oxathianes prior to cleavage, oxidizing with sodium chlorite following cleavage, esterifying and debenzylating. A method for measuring the enantiomeric purity of glycols RCHOHCH₂OH by conversion to 2-phenyl-l,3-dioxolanes with benzaldehyde, followed by proton NMR analysis of the resulting 2-phenyl-4-alkyl-l,3-dioxolane diastereomer pair in the presence of a chiral europium shift reagent is described.