INTERNAL-ROTATION AROUND SINGLE BONDS AND CONFORMATIONAL PREFERENCES IN HETEROCYCLIC-ANALOGS OF BENZYL METHYL SULFOXIDE STUDIED WITH NMR TECHNIQUES

The conformational equilibrium related to the internal rotation processes occurring in sulphoxides of the type ArCH2SOCH3 (where Ar=2-thienyl, 2-furyl, 2-pyridinyl and (3-methyl)2-pyridinyl rings) were studied with H-1 and C-13 NMR spectroscopy. Proton chemical shifts and long-range coupling constants (n)J(H, H) were obtained from the iterative analysis of the multiplets and were employed, together with C-13 chemical shifts, long-range (n)J(C, H) and relaxation parameters (NOE and non-selective T-1 values) to obtain stereochemical relationships between the protons present in these molecules. Conformational predictions at a qualitative level were also derived from total molecular energies calculated with the semi-empirical AM1/MNDO method as a function of internal coordinates. The different approaches converged to indicate that the heterocyclic rings adopt an average orientation similar to the perpendicular orientation of the phenyl ring in benzyl methyl sulphoxide and, as regards rotation around the CH2-S bond, the prevalent conformer shows that the methyl group is symmetrically oriented with respect to the methylenic protons, The barriers for internal rotation are rather low and the equilibrium between conformers is dependent on the medium properties. Attempts to obtain conformational results were performed for the molecule of omeprazole, an antiulcer drug which contains the ArCH2SO-R moiety (Ar and R are substituted 2-pyridinyl and 2-benzimidazolyl groups, respectively). With respect to the other compounds examined, the orientation of the Ar ring does not significantly differ and the benzimidazole ring seems to prefer an orientation stereochemically equivalent to that of the methyl group

Electron Transfer in the Reactions of Organic Trichloromethyl Derivatives with Iron(II) Chloride

Reduction of trichloromethyl derivatives RCCl3 [1, R = Ph;2, R = PhC(O); 3, R = EtOC(O)] with iron(II) chloride in acetonitrile, has been studied in order to examine the mechanism of the electron transfer (ET) process and the reactions of the radicals formed. Substrates 1-3 afforded different product compositions and the cause was identified as differences in the reactivity of radicals which is substantially of two types: reductive coupling and proton abstraction after further reduction to a carbanion coordinated to the metal ion. Compound 1 gave only coupling products, compound 2 only hydrogenated products and compound 3 a mixture of coupling and hydrogenated products depending on experimental conditions. Proton abstraction by the carbanion was found to occur from water molecules, which should be present in the coordination shell of the metal ion, and not from the solvent. The different behaviour of compounds 1-3 is attributed to the presence of substituents which are able to stabilize the radical and carbanionic intermediates. Rate constants at different temperatures were measured and the activation parameters calculated. The three substrates differ only slightly in reaction rates, in the order 1 > 2 > 3. Activation enthalpies are very close to each other and this agrees with the almost equal values of C-Cl bond dissociation energies of compounds 1-3, empirically determined. Large, negative entropies of activation were found, suggesting that an ordered activation complex should be formed in order that electron transfer from the metal ion to the organic halide can take place

Long-range 13C-1H Spin-Spin Coupling Constants in the Conformational Analysis of Formil Derivatives of Furan and Thiophene, Magn. Reson. Chem., 25, 804-810

The long-range 13C-1H Constants were employed in the conformational analysis of formil derivatives of furan and thiophen

CONFORMATIONAL PREFERENCE OF THE METHYLSULFINYL GROUP BONDED TO THE FURAN AND THIOPHENE RINGS - A THEORETICAL APPROACH

The ground state conformations and transition states for conformer interconversion in the two isomers of the of furan (1 and 2) and thiophene (3 and 4) were identified through a theoretical approach based on ab-initio molecular orbital calculations. Two minima and two transition states were found in the potential energy profiles for all the molecules, but the behaviour of 2-methylsulphinyl furan (1) differs somewhat from that of the other compounds. The minima correspond to the two orientations of the S-O bond with respect to the heterocyclic heteroatom X (X = O or S), labelled X,O-cis an X,O-trans. The conformer having the S-O bond oriented s-cis with respect to the internal double bond with higher pi density (X,O-cis for the 3-methylsulphinyl derivatives and X,O-trans for the 2-methylsulphinyl derivatives) has a twist angle phi (between the S-O bond and the heterocyclic ring) of a few degrees. Larger distortions are present in the conformers with opposite orientation of the S-O bond, and the twist angle has the highest value (phi = 62.8-degrees) in compound 1. The transition states correspond to the methyl group being nearly coplanar with the heterocyclic ring and this situation seems to be due mostly to a loss of pi electron delocalization. More complex is the transition state situation for compound 1, since a barrier in the potential energy for internal rotation is imposed also by the repulsion between the heterocyclic and sulphinyl oxygen atoms. The conformer populations were estimated from the potential energ

Conformational Behaviour of Organic carbonyl Compounds. Part 2. Aldehydes and Acetyl Derivatives of Condensed Aromatic Hydrocarbons

The relative conformer stability in a number of acetyl and formyl derivatives of condensed hydrocarbons has been determined by the lanthanide induced shift (LIS) method and by simulating the experimental chemical shifts. For the aldehyde of naphtalene the conformational results were confirmed by examining the nmr spectra of model compounds with known probable conformation. In condensed hydrocarbons containing carbonyl substituents the behviour found may be substantially related to three distinct situations, those comparable to the alpha- and beta -positions of naphtalene and overcrowded positions comparable to position 4 in phenanthrene. Calculation of the conformational behaviour by the semi-empirical methods provide qualitative correct results only for systems where steric interactions are small

Conformational Behaviour of Organic carbonyl Compounds. Part 2. Aldehydes and Acetyl Derivatives of Condensed Aromatic Hydrocarbons

The relative conformer stability in a number of acetyl and formyl derivatives of condensed hydrocarbons has been determined by the lanthanide induced shift (LIS) method and by simulating the experimental chemical shifts. For the aldehyde of naphtalene the conformational results were confirmed by examining the nmr spectra of model compounds with known probable conformation. In condensed hydrocarbons containing carbonyl substituents the behviour found may be substantially related to three distinct situations, those comparable to the alpha- and beta -positions of naphtalene and overcrowded positions comparable to position 4 in phenanthrene. Calculation of the conformational behaviour by the semi-empirical methods provide qualitative correct results only for systems where steric interactions are small

A 1H NMR Spectra of the 2-Trifluoroacetyl Derivatives of Benzo[b]furan and Benzo[b]thiophene

Proton magnetic resonance spectroscopy of title compounds were carefully examined