Showing papers on "Steric effects published in 1998"

Reactivity of Monolayer-Protected Gold Cluster Molecules: Steric Effects

Abstract: The steric environment of alkanethiolate ligand shells of monolayer-protected gold cluster (MPCs) molecules has been investigated in three ways. First, the SN2 reactivity of ω-bromoalkanethiolate-functionalized MPCs with primary amines has been shown to respond to the steric bulk of the incoming nucleophile (rates of n-propylamine> isopropylamine> tert-butylamine), and to the relative chain lengths of ω-bromoalkanethiolate and surrounding alkanethiolate chains (rates of C12:C12Br > C12:C8Br > C12:C3Br). Also, unlike 2D-SAMs, ω-bromo-functionalized MPCs and primary alkyl halide monomers (RBr) have comparable SN2 reactivities. These results are significant in that little previously was known about the chemical reactivities of the monolayers on MPCs, and in that the poly-functional ω-bromoalkanethiolate MPCs are shown to be highly reactive, i.e., as many as 20 SN2 displacements occur per cluster molecule. Second, steric aspects of alkanethiolate monolayers on Au clusters are shown to affect the rate of cyani...

Molecular Mechanisms Controlling the Self-Assembly Process of Polyelectrolyte Multilayers

Abstract: The distance dependent interaction between polyelectrolyte-covered mica surfaces in aqueous solution was investigated with the surface forces apparatus. We find the following: (i) The surface charge changes sign, when an oppositely charged polyelectrolyte from a concentrated polyelectrolyte solution is adsorbed. (ii) Tails and loops of the adsorbed polyions dangle into the bulk phase, inducing a small steric force. If polycations and poyanions are adsorbed on top of each other, a strong short range attractive force is seen due to ion-pair formation after crossing a large repulsive electrostatic/steric barrier. (iii) Obviously, after polyelectrolyte adsorption, there are still nonoccupied binding places (point charges) on the substrate. We show that these adsorption properties regulate the build-up of polyelectrolyte multilayers: Ion pairs between oppositely charged polyion segments and the substrate are formed, until the surface charge is inversed. The electrostatic barrier limits the adsorbed amount, g...

Rational Design of Benzyl-Type Protecting Groups Allows Sequential Deprotection of Hydroxyl Groups by Catalytic Hydrogenolysis

Abstract: Benzyl protection of a hydroxyl group is one of the most frequently used procedures in synthesis because of the mild conditions involved in its removal by catalytic hydrogenolysis.1-3 The synthesis of polyhydroxylated compounds often requires orthogonal protecting strategies to distinguish between hydroxyl groups. It would be highly desirable to develop a range of benzyl-type protecting groups with different reactivities that can be sequentially removed via catalytic hydrogenolysis. This requires a detailed understanding of the mechanism of the cleavage of the benzyl oxygen bond by the palladium hydrogen species. Recently, we have determined the amphipolar nature of the palladium hydrogen bond (modes a, Mδ+ Hδ-, or b, MδHδ+) in both homogeneous4 and heterogeneous5 hydrogenation of alkenes. This has led us to test whether the electronic properties of the aromatic group can influence the rate of cleavage, which should in turn guide the development of hydroxyl protecting groups with different reactivities. The results in Table 1 show that the rate of debenzylation can be dramatically affected by the electronic properties of the aromatic ring. The substitution of the electron-withdrawing trifluoromethyl group onto the aromatic ring severely retards debenzylation under 1 atm of hydrogen. In contrast, there is considerable acceleration by electrondonating substituents, which suggests that the benzylic carbon bears a partial positive charge in the transition state. The hydrogenolysis of benzyl alcohols carried out in acetic acid has shown that protonation of the hydroxyl group is essential for the cleavage of the carbon-oxygen bond.6 Under the neutral conditions in our study, the reaction may occur by protonation of the benzyl oxygen atom, through the operation of mode b, MδHδ+, to give a positively charged benzylic carbon. Alternativly, it is possible that palladium could act as a Lewis acid and coordinate to the benzyl oxygen atom to promote the same electron-deficient transition state (mode a, Mδ+ Hδ-). The large difference in reactivity within this range of substituted benzyl groups suggests that they can be sequentially deprotected, therefore proving useful in multistep synthesis. To test the synthetic application of these groups, competition experiments were conducted on model systems with two differently substituted benzyl groups attached to ethanediol (Scheme 1a). Surprisingly, the benzyl group was cleaved first in competition with any of the substituted benzyl groups. This phenomenon has been observed with the 4-methoxybenzyl group (PMB); however, no explanation was proposed.7,8 The results with the linker experiments (Scheme 1a) seem to contradict those obtained when only one benzyl group is involved (Table 1). Surface scientists have determined that the aromatic ring lies flat on the metal surface for optimal coordination.9,10 It is possible that substitution on the aromatic ring could have an adverse steric effect that would interfere with the planar geometry required for effective binding and thus reduce its affinity for the metal surface. The linker experiments show that the limited number of active sites on the palladium surface could lead to a competition for adsorption sites between substituted and unsubstituted benzyl groups. This may explain why the least substituted benzyl group, although not electronically favored, can still be preferentially cleaved. It is clear that for the rational design of selective benzyl type protecting groups both electronic factors and adsorption must be taken into account. For synthetic purposes, it would be desirable to find a more labile group than the benzyl group for protection of the hydroxyl functionality. We anticipated that the 2-naphthylmethyl (NAP) group would fulfill these criteria: it is electron rich and should have a (1) Greene, T. W.; Wuts, P. G. M. In Protective Groups in Organic Synthesis; John Wiley & Sons, Inc.: New York, 1991. (2) (a) Czernecki, S.; Georgoulis, C.; Provelenghiou, C. Tetrahedron Lett. 1976, 3535. (b) Iverson T.; Bundle K. R. J. Chem. Soc., Chem. Commun., 1981, 1240. (3) Czech, B. P.; Bartsch, R. A. J. Org. Chem. 1984, 49, 4076. (4) Yu, J.; Spencer, J. B. J. Am. Chem. Soc. 1997, 119, 5257. (5) Yu, J.; Spencer, J. B. J. Org. Chem. 1997, 62, 8618. (6) Kieboom, A. P. G.; De Kreuk, J. F.; Van Berkum, H. J. Catal. 1971, 20, 58. (7) Srikrishna, A.; Viswajanani, J. A.; Sattigeri, J. A.; Vijaykumar, D. J. Org. Chem. 1995, 60, 5961. (8) Sajiki, H.; Kuno, H.; Hirota, K. Tetrahedron Lett. 1997, 38, 399. (9) Lin, R. F.; Koestner, R. J.; Van Hove, M. A.; Somorjai, G. A. Surf. Sci. 1983, 161. (10) Held, G.; Bessent, M. P.; Titmuss, S.; King, D. A. J. Chem. Phys. 1996, 11305. Table 1a

Systematic Variation of Bidentate Ligands Used in Aryl Halide Amination. Unexpected Effects of Steric, Electronic, and Geometric Perturbations

Abstract: This paper presents effects of varying bidentate phosphine steric properties, electronic properties, and bite angle on product ratios in the amination of aryl bromides. Comparisons of the ratios of...

Ab Initio Calculations on CO2 Binding to Carbonyl Groups

Abstract: Ab initio molecular orbital calculations were performed at the SCF and MP2 levels, using a 6-31G basis set, for complexes of CO2 with carbonyl compounds. The specific interaction between CO2 and the carbonyl oxygen can be described as a Lewis acid−base reaction. Two different geometries, one having C2v symmetry and the other having Cs symmetry, were studied. The Cs symmetry was found to yield stronger binding of the CO2 complexes. The degeneracy of the ν2 bending mode in free CO2 was lifted when the CO2 was bound. The calculated ν2 splittings at the SCF level, using a 6-31G basis set, were comparable to literature values determined by IR spectroscopy of CO2-impregnated polymers. When steric hindrance was present, the binding energy of CO2 to carbonyls was reduced, resulting in lower ν2 splittings. The interaction energy between benzene and CO2 was determined to be much lower than that associated with a carbonyl oxygen and CO2. The preference of CO2 for the carbonyl group over the benzene ring, along with ...

Synthesis of Optically Active α-Hydroxy Carbonyl Compounds by the Catalytic, Enantioselective Oxidation of Silyl Enol Ethers and Ketene Acetals with (Salen)manganese(III) Complexes

Abstract: A set of silyl enol ethers and ketene acetals 1a−h with α- and/or β-phenyl as well as alkyl substituents of different steric bulk has been submitted to the enantioselective catalytic oxidation by chiral (salen)MnIII complexes 3. Highest conversions and best enantioselectivities have been obtained with bleach rather than iodosobenzene as oxygen source for the active oxo−metal species. With regard to substrate structure, ee values up to 89% have been achieved for enol ethers with short and unbranched alkyl substituents at the siloxy position. While β-phenyl groups are beneficial for enantiofacial control, phenyl substituents α to the siloxy functionality result in lower ee values, while the diphenyl-substituted derivative 1d displays the lowest stereoselectivity. The fact that β- versus α-phenyl substituents exhibit not only differences in the magnitude but also in the sense (opposite absolute product configuration) of the stereoselectivity may be utilized as a valuable mechanistic probe to assess steric an...

To Bend or Not To Bend: Dilemma of the Edge-Sharing Binuclear Square Planar Complexes of d8 Transition Metal Ions

Abstract: The binuclear complexes of d8 transition metal ions of type [L2M(μ-XRn)2ML2] (n = 0 to 2) show a wide variety of bending angles between the coordination planes of the two metal atoms. A theoretical and structural analysis of those compounds with unsubstituted bridges, [L2M(μ-X)2ML2], tries to unravel the factors that determine the degree of bending of such compounds. A rationale is given for the structures of 139 crystallographically independent molecules. A driving force for bending of the molecules is the attractive metal···metal interaction that results from donor−acceptor interactions between the dz2 and pz orbitals of the two metal atoms and is modulated by the nature of (a) the metal atom, (b) the terminal ligands, and (c) the bridging atoms. In all cases the energy difference between the planar and the bent form is within the 10 kcal/mol range, and steric effects seem to be important in preventing bending only for the bulkiest terminal ligands. For the studied bridging atoms, the stability of the b...

Ethene−Norbornene Copolymerization with Homogeneous Metallocene and Half-Sandwich Catalysts: Kinetics and Relationships between Catalyst Structure and Polymer Structure. 4. Development of Molecular Weights

Abstract: The molecular weights of ethene−norbornene copolymers, produced with various metallocene− and amidocyclopentadienyl−methylaluminoxane (MAO) catalysts, have been determined by high-temperature gel-permeation chromatography: with one exception, increasing molecular weights were found with an increasing norbornene content in the copolymer. This observation is due to the fact that the β-hydride elimination process is not possible in the case of norbornene, because of special steric conditions of the cis-2,3-exo inserted norbornene; other possible termination reactions are discussed, considering the specialties of the norbornene. The effect of the catalyst structure on the molecular weights is discussed in terms of steric and electronic factors of the different ligands: sterically less hindered ligands produce ethene−norbornene copolymers with relatively low molecular weights; ligands with a larger extension and electron-pushing effect such as the fluorenyl ligand, induced the formation of high molecular wei...

Reactivity of niobium clusters with nitrogen and deuterium

Abstract: Absolute rate coefficients are reported for reactions of Nbn clusters (n=2–20) with D2 and N2 at 280, 300, and 370 K. Most clusters are highly reactive but there are conspicuous exceptions at n=8, 10, and 16 for both D2 and N2. The origin of this trend in reactivity with cluster size and the reason why D2 and N2 show similar trends are discussed. Density functional theory (DFT) electronic structure calculations have been used to investigate the details of the reactions for the smallest clusters Nb2 and Nb8 with H2 and N2. The steric and electronic requirements for dissociation of H2 and N2 are described in terms of frontier orbital interactions. The main conclusion from the DFT calculations is that complete dissociation of H2 or N2 requires charge transfer by transit of an avoided crossing between neutral and ionic potentials. This idea is extended to larger clusters by using a simple charge transfer model that predicts an inverse correlation between reactivity and an appropriately defined effective ionization potential. Such a correlation is observed and indicates that the effective ionization potential is the dominant influence on reactivity.

Computational Evidence of the Importance of Substituent Bulk on Agostic Interactions in Ir(H)2(PtBu2Ph)2

Abstract: While Ir(H)2(PtBu2Ph)2+ has been shown experimentally to have two agostic tBu groups, ab initio B3LYP calculations on IrH2[P(Et)H2]2+ show that the CH3 group of the phosphine ligand does not form any agostic bond with the strongly electron-deficient (14-valence electron) metal. In contrast, integrated molecular mechanics/molecular orbital (IMOMM) calculations on the full complex Ir(H)2(PtBu2Ph)2+ duplicate the experimentally observed agostic interaction. Thus, at least in this case, the agostic interaction is due in part to the trapping of a C−H bond in the vicinity of the metal by the steric effects of the other groups of the bulky phosphine. This necessity of steric “constraint” identifies an additional influential factor for the agostic interaction.

Structure and Base Pairing Properties of a Replicable Nonpolar Isostere for Deoxyadenosine.

Abstract: We report the synthesis, structure, and pairing properties in DNA of an isostere for deoxyadenosine which lacks all hydrogen-bonding functionality on the Watson-Crick pairing edge. A deoxyribo-nucleoside derivative of 4-methylbenzimidazole (1), which was recently shown to be inserted into DNA by Klenow DNA polymerase (Morales, J. C.; Kool, E. T. Nature Struct. Biol.1998, 5, 950), is prepared from 1-chloro-2-deoxy-3,5-bis-O-p-toluoyl-α-D-erythro-pentofuranose. The X-ray crystal structure of the nucleoside confirms that the compound is a close steric match for deoxyadenosine (2), although the methylbenzimidazole base is in the syn glycosidic orientation in the crystal. In D(2)O solution, 1H NMR studies show that 1 and 2 have similar (60% vs 70% S) sugar conformations and anti glycosidic orientations. Compound 1 is incorporated into a 12mer oligodeoxynucleotide and its base pairing properties in duplexes assessed by thermal denaturation. The results show that 1 has low affinity for the four natural bases but displays a stronger preference for being situated opposite a nonpolar difluorotoluene nucleoside analogue of thymine (3). The structural similarities of 1 and 2, combined with recent polymerase studies, add support to the hypothesis that steric complementarity plays an important role in base pair replication by polymerase enzymes and that Watson-Crick hydrogen bonds are not absolute requirements. Compound 1 should have significant utility as a probe of the importance of electrostatic effects in protein-DNA and protein-nucleotide binding as well as in DNA replication.

Catalytic Asymmetric Epoxidation of Aldehydes. Optimization, Mechanism, and Discovery of Stereoelectronic Control Involving a Combination of Anomeric and Cieplak Effects in Sulfur Ylide Epoxidations with Chiral 1,3-Oxathianes

Abstract: A range of 1,3-oxathianes based on camphorsulfonic acid have been prepared and tested in the catalytic asymmetric epoxidation of carbonyl compounds. It was found that the 1,3-oxathiane derived from acetaldehyde 5b gave the highest yield and enantioselectivity in the epoxidation process. The enantioselectivity was independent of the solvent and metal catalyst used (although yields were dependent on both). The optimum conditions were applied to a range of aldehydes, and good enantioselectivities and diastereoselectivities were observed. The origin of the enantioselectivity was probed, and in particular the role of the oxygen of the 1,3-oxathiane was investigated. Thus, the sulfur and carbon analogues of the camphorsulfonic acid based 1,3-oxathiane (derived from formaldehyde) were prepared (i.e., 1,3-dithiane and thiane analogues). With this series of analogues the steric effects are minimized so that the electronic effects can be investigated. The series of compounds was reacted in the catalytic cycle with ...

Replication of non-hydrogen bonded bases by dna polymerases : a mechanism for steric matching

Abstract: Recent experiments have presented evidence that Watson–Crick hydrogen bonds in a base pair are not absolute requirements for efficient synthesis of that pair by DNA polymerase enzymes. Here we examine quantitative steady-state kinetic data from several published studies involving poorly hydrogen-bonding DNA base analogues and adducts, and analyze the results in terms of solvation, hydrogen bonding, and steric effects. We propose a mechanism that can explain the surprising lack of hydrogen-bonding requirement accompanied by significant selectivity in pairing. This hypothesis makes use of steric matching, enforced both by the tightly confined polymerase active site and by the DNA backbone, as a chief factor determining nucleotide selection during DNA synthesis. The results also suggest that hydrogen bonds from bases to water (solvation) may be important in increasing the effective size of DNA bases, which may help prevent misinsertion of small bases opposite each other. © 1998 John Wiley & Sons, Inc. Biopoly 48: 3–17, 1998

Theoretical Studies of Steric Effects on Intraligand Electron Delocalization: Implications for the Temporal Evolution of MLCT Excited States

Abstract: The effect of steric bulk on electron delocalization in 4-arylpyridines has been studied by computational methods. Ab initio (HF, UHF, ROHF, MP2, UMP2, and ROMP2) as well as density functional theory (USVWN and UB-LYP) approaches were applied to a series of molecules and their corresponding anions. These molecules are put forth as models for the ground and MLCT excited states of three polypyridyl ligands that were the subject of a recent report on the effects of sterics and delocalization on the photophysics of several Ru II complexes (Damrauer, et al. J. Am. Chem. Soc.1997, 119, 8253). The present study finds that, in the series 4-phenylpyridine, 4-(o-tolyl)pyridine, and 4-(2,6-dimethylphenyl)pyridine, the steric effect of the ortho-methyl groups serves to increase the dihedral angle between the pyridyl and phenyl rings of the neutral compounds from ca. 45° in the case of 4-phenylpyridine to ca. 65° and 90° in the mono- and dimethylated compounds, respectively. These results are generally consistent with the single-crystal X-ray structures of the three corresponding bipyridines, also reported herein. Upon one-electron reduction, calculations on all three model ligands reveal a preference for a coplanar structure, with the optimized geometries reflecting a balance between an energetic stabilization gained via conjugation in the planar form and unfavorable steric interactions between the methyl group(s) of the 4-aryl substituent and the pyridyl protons ortho to the central C-C bond. Calculated dihedral angles were 0°,25°, and45° for 4-phenyl-, 4-(o-tolyl)-, and 4-(2,6dimethyl)pyridine, respectively. Finally, a simulation of the Franck -Condon state evolution of MLCT states of molecules containing the bipyridyl analogues of the three models was carried out by computing singlepoint energies of each compound as its monoanion in the optimized neutral geometry. Comparison of these energies with those of the fully optimized anions revealed effective reorganization energies of 4 -7 kcal/mol for 4-phenylpyridine, 4-7 kcal/mol for 4-(o-tolyl)pyridine, and ca. 6 kcal/mol for 4-(2,6-dimethylphenyl)pyridine. The implications of these results as they pertain to ultrafast spectroscopic studies of MLCT excitedstate evolution in the corresponding Ru II bipyridyl complexes are discussed.

Intra- and intermolecular hydrogen bonding of 2-methoxyethanol and 2-butoxyethanol in n-hexane

Abstract: Glycol−ether compounds such as 2-methoxyethanol (CH3OCH2CH2OH) and 2-butoxyethanol [CH3(CH2)3OCH2CH2OH] form both intra- and intermolecular hydrogen bonds. Using Fourier transform infrared spectroscopy, we have measured extent of intra- and intermolecular hydrogen bonding in these compounds dissolved in n-hexane at varying concentrations and temperatures. Intramolecular hydrogen bonds are present at all conditions, whereas intermolecular bonds appear at higher concentrations. Using lattice-fluid-hydrogen-bonding theory, equilibrium constants for the formation of intra- and intermolecular hydrogen bonds are determined. The results show that the equilibrium constant for intermolecular bond formation is approximately 6 times the intramolecular equilibrium constant for 2-methoxyethanol systems at 35 °C. Experiments at higher temperature, 45 °C, with 2-methoxyethanol show less hydrogen bonding as expected due to higher thermal energy. Due to steric hindrance, 2-butoxyethanol has a lower degree of hydrogen bond...

Theoretical Prediction and Experimental Tests of Conformational Switches in Transition States of Diels−Alder and 1,3-Dipolar Cycloadditions to Enol Ethers

Abstract: Transition structures for the cycloadditions of butadiene, acrolein, nitrosoethylene, and methylenenitrone to 1-butene, silyl vinyl ether, and methyl vinyl ether have been located using ab initio RHF theory with the 3-21G basis set and with density functional theory using the Becke3LYP functional and the 6-31G* basis set. The computational results show that there is a switch in the conformation of the enol ether from syn (COCC = 0°), which is favored by 2.3 kcal/mol in the reactant, to anti (COCC = 180°), which is favored by 1.2−6.6 kcal/mol in the various transition structures studied here. The results are consistent with the experimental stereoselectivities in reactions of chiral enol ethers observed by Denmark and Reissig. The preference of the anti conformation in the transition structures is due primarily to electrostatic effects and, to a lesser extent, steric effects. The preference is predicted to be influenced significantly by polar solvents. The magnitude of this preference was calculated theore...

Hydrogen-bond basicity pkhb scale of six-membered aromatic n-heterocycles

Abstract: Using 4-fluorophenol as a reference hydrogen-bond donor, equilibrium constants, Kf, for the formation of 1∶1 hydrogen-bonded complexes have been obtained by FTIR spectrometry for 65 six-membered N-heteroaromatics of widely differing structures, in CCl4 at 298 K The pKHB scale shows that most Nsp2 bases are weaker hydrogen-bond bases than many oxygen bases This scale extends from the hypobasic pentafluoropyridine, illustrating the electron-withdrawing field effect of fluoro substituents, to push–pull 4-NR2-pyridines, illustrating the resonance effect of the 4-NR2 substituents which donate electrons in the order NH2 < piperidino < NMe2 < NEt2 < pyrrolidino A spectroscopic scale is constructed from the IR frequency shift Δν(OH) of methanol hydrogen-bonded to N-heteroaromatics The thermodynamic pKHB scale correlates with the Δν(OH) scale, but 2-substituted pyridines deviate markedly These deviations are attributed to, and allow the semi-quantitative determination of: (i) steric effects, most important in 7,8-benzoquinoline; (ii) lone pair–lone pair repulsions, most important in 1,2-diazines; and (iii) lone pair–bond pair repulsions, most important in 2,6-difluoropyridine IR spectra show the fixation of 4-fluorophenol to the nitrile nitrogen of 2-, 3- and 4-cyanopyridines, to the carbonyl oxygen of 3-COOMe, 3-COPh and 4-COMe-pyridines, and to the ether oxygen of 2-methoxypyridine, in addition to the fixation to the pyridine nitrogen A cyclic complex, with both NH· · ·O and OH· · ·N hydrogen bonds, is formed with 2-amino- and 2-methylamino-pyridines

Proximate Nitroxide Ligands in the Coordination Spheres of Manganese(II) and Nickel(II) Ions. Precursors for High-Dimensional Molecular Magnetic Materials.

Abstract: The chelating nitroxide ligands 2-(2-pyridyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazolyl-3-oxide-1-oxy (NITPy, 1), 2-(2-imidazolyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazolyl-3-oxide-1-oxy (NITImH, 2), and 2-(2-benzimidazolyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazolyl-3-oxide-1-oxy (NITBzImH, 3) and some of their transition metal complexes (Mn(II), Ni(II), Zn(II)) have been prepared and characterized by X-ray diffraction techniques and magnetic susceptibility measurements. All complexes are four- (or three-) spin systems where the metal coordination sphere is free of ancillary ligands because of the chelate effect which enforces the coordination of the oxyl group. The fac or mer nature of these species depends on the metal ions and on the steric demand of the ligand. It has been found that crystal packing is an important driving force toward the fac modification when steric requirements are not important. Crystal packing is probably also the cause of the noncentrosymmetric space group observed for the derivatives of NITPy. For the Zn(II) complex of NITImH, a moderate inter-nitroxide interaction within the metal coordination sphere of -14 cm(-)(1) is estimated. However, due to the modification of the spin distribution upon complexation, this interaction does not play a major role in the other complexes, where strong antiferromagnetic metal-nitroxide interactions (H = -2JS(i).S(j), -111 < J < -53 cm(-)(1)) are operative. The derivatives of NITImH are precursors of extended species which would be obtained by deprotonation of the ligand.

Using Hydrogen Bonding to Control Carbamate C-N Rotamer Equilibria.

Abstract: In chloroform solution, the syn/anti rotamer ratios for N-(2-pyridyl)carbamates, 3, and N-phenylcarbamates, 4, are close to 0.05. Addition of the double hydrogen bonding acetic acid moderately stabilizes the syn rotamer of 4, but has no measurable effect on the syn/anti ratio for 3. Conversely, the hydrogen bond donor-acceptor-donor triad in 2,6-bis(octylamido)pyridine, 1, strongly stabilizes the syn rotamer of 3, but has no effect on the syn/anti ratio for 4. The K(a) for syn-3:1 is 10(3)-10(4) times higher than the K(a) for anti-3:1. This implies that the alkoxy oxygen in anti-3 is a much poorer hydrogen bond acceptor than the carbonyl oxygen in syn-3, most likely because of a combination of steric and electrostatic factors.

Structure and molecular interactions of anti-thyroid drugs. Part 3.1 Methimazole: a diiodine sponge

Abstract: The anti-thyroid drug methimazole functions as a diiodine sponge. Its thione tautomer forms with diiodine a very stable electron donor–acceptor complex (Kf = 36 600 l mol–1 in CCl4), stabilized in a more polar medium (Kf = 92 400 l mol–1 in CH2Cl2). Two stereoisomeric complexes, one planar on the non-bonding sulfur lone pair and the other perpendicular on the sulfur π electrons, are found in solution to be under steric control. The position of the charge-transfer band of many diiodine complexes of thioamides and thioureas allows the prediction of their geometry. The sulfur–iodine coordination is assisted by intramolecular hydrogen bonding NH· · ·I. This iodine amphoterism is explained by the anisotropy of its electrostatic potential surface. Hard and soft acid–base chemistry might explain the two mechanisms of action of anti-thyroid drugs, the inhibition of thyroid peroxidase via coordination to the hard heme group and the trapping of oxidized iodides via complexation of soft iodinated Lewis acids.

Conformational Analysis (ab Initio HF/3-21G*) and Optical Properties of Symmetrically Disubstituted Terthiophenes

Abstract: We report a conformational analysis of several substituted terthiophenes using ab initio calculations performed at the HF/3-21G* level. Geometries of terthiophenes having methoxy substituents in 3,3‘‘ positions (DMOTT), methyl groups in the same positions (DMTT), and ethyl substituents in 3‘,4‘ positions (DETT) are compared with that of the unsubstituted molecule (TT). For all these symmetrical molecules, it is observed that the two dihedral angles are independent of each other. The most stable conformation of TT is found for dihedral angles θ = φ = 147.2°, whereas three maxima are located at 0°, 90°, and 180°. The insertion of methoxy groups in 3,3‘‘ positions favors a more planar conformation with a higher rotational barrier at 90°. This behavior is explained by the electron donor properties of the methoxy groups. By contrast, the addition of two methyl groups at the same positions induces a twisting in the molecule which is caused by the steric hindrance between the methyl substituents and the sulfur a...

Controlling the Frequency of Macrocyclic Ring Rotation in Benzylic Amide [2]Catenanes

Abstract: A combination of variable-temperature 1H NMR spectroscopy and molecular mechanics calculations have been used to probe the factors that determine the rate of macrocyclic ring rotation in benzylic amide [2]catenanes. The results show that the interlocked macrocycle dynamics are governed by a delicate combination of steric effects, intricate inter-macrocyclic arrays of hydrogen bonds, π−π stacking, and T herringbone-type interactions. A cascade of hydrogen-bond ruptures and formations is the principal event during circumvolution (complete rotation of one macrocyclic ring about the other) but is accompanied by a series of cooperative conformational and co-conformational rearrangements that help to stabilize the energy of the molecule. The experimental picture is consistent both when activation energies are measured from the coalescence of NMR signals and when rate constants are directly measured by spin polarization transfer by selective inversion recovery (SPT-SIR) methods. The nature of the circumrotationa...

Stereoselective Alkylations in Rigid Systems. Effect of Remote Substituents on π-Facial Additions to Lactam Enolates. Stereoelectronic and Steric Effects

Abstract: A series of chiral bicyclic lactams has been studied by both experiment and ab initio molecular orbital calculations. The facial selectivity of the alkylation of their enolates shows a high degree of endo or exo entry, depending upon certain substituents and their positions in the lactams. The suggested reasons for the exo or endo selectivity for alkylation were determined to be purely electronic or purely steric in certain instances. The results of the selectivity study now allow the asymmetric synthesis of various ketones, acids, and pyrrolidines in either enantiomeric form based on the choice of lactam employed.

Strong Trans Influence Methoxymethyl Ligand in B(12) Cobaloxime and Imine/Oxime Model Complexes: Structural, Spectroscopic, and Molecular Mechanics Investigations

Abstract: The CH(2)OCH(3) ligand has a large trans influence comparable to that of bulky alkyl groups but lacks the complication of marked steric effects. However, crystals of model complexes with this ligand have proved difficult to obtain. The crystal structures of the cobaloximes reported here, Me(3)BzmCo(DH)(2)CH(2)OCH(3).0.6CH(3)OH (1) and 4-MepyCo(DH)(2)CH(2)OCH(3) (2) [DH = monoanion of dimethylglyoxime, Me(3)Bzm = 1,5,6-trimethylbenzimidazole, and 4-Mepy = 4-methylpyridine], triple the number of cobaloxime structures with CH(2)OCH(3). Also, these are the first structures in this class of models with an N-donor planar heterocyclic axial donor ligand, L. The planes of the Me(3)Bzm and 4-Mepy ligands are almost perpendicular to the respective planes of the four equatorial DH nitrogen donors and bisect the (O(-))N-Co-N(OH) angles. The Co-N(L) bond distances average 2.096(2) A, confirming the strong trans influence of CH(2)OCH(3). Geometry optimization via molecular mechanics using MacroModel 5.0 and an AMBER-type force field was applied to both cobaloxime-type and imine/oxime-type B(12) models. In our initial work with some imine/oxime models, the calculated structures did not compare well to the solid-state structures. Therefore, adjustments to the force field were evaluated. The major adjustment that improved the fit of the computed and experimental structures was an approximately 10% reduction of the van der Waals (vdw) parameters for both the N donors and the C(sp(2)) atoms linked to the N donors; this adjustment may reflect the electron-withdrawing effect of the metal center. Analysis of (1)H-(13)C coupling constants of Me(3)Bzm lends support to the concept that the atoms in the ligands were modified, but only slightly, by the metal center. To reproduce the dependence of geometric features on the trans influence, different force field parameters for L-Co bonds were used for compounds with weak (Cl) and those with strong (CH(2)OCH(3)) trans influence ligands. These small modifications allowed us to model the structural features of both classes of models well.

Synthesis and Properties of Octaethylporphinato(arenethiolato)iron(III) Complexes with Intramolecular NH···S Hydrogen Bond: Chemical Function of the Hydrogen Bond

Abstract: Iron(III) porphinate complexes of arenethiolate having single or double NH···S hydrogen bonds at the axial position, [FeIII(OEP){S-2,6-(RCONH)2C6H3}] (R = CF3 (1), CH3 (2)) or [FeIII(OEP)(S-2-RCONHC6H4)] (R = CF3 (3), CH3 (4), t-Bu (5)), were synthesized as models of P-450 and chloroperoxidase. The presence of an NH···S hydrogen bond in these complexes is confirmed by their crystal structures in the solid state, the IR shift of the amide NH band and the direct through-bond contact-shift of the amide 2H NMR signal in benzene. The NH···S hydrogen bond elongates the Fe−S bond distance, stabilizes the Fe(III) state, protects the complexes from decomposition by air and moisture, and shifts the redox to more positive potentials. These functions by the hydrogen bond are more significant than the effect of steric hindrance.