Quantitative assessment of substituent effects on cation-π interactions using molecular electrostatic potential topography

A molecular electrostatic potential (MESP) topography based approach has been proposed to quantify the substituent effects on cation-π interactions in complexes of mono-, di-, tri-, and hexasubstituted benzenes with Li(+), Na(+), K(+), and NH(4)(+). The MESP minimum (V(min)) on the π-region of C(6)H(5)X showed strong linear dependency to the cation-π interaction energy, E(M(+)). Further, cation-π distance correlated well with V(min)-π distance. The difference between V(min) of C(6)H(5)X and C(6)H(6) (ΔV(min)) is proposed as a good parameter to quantify the substituent effect on cation-π interaction. Compared to benzene, electron-donating groups stabilize the di-, tri-, and hexasubstituted cation-π complexes while electron-withdrawing groups destabilize them. In multiple substituted complexes, E(M(+)) is almost equal (～95%) to the sum of the individual substituent contributions (E(M(+)) ≈ Σ(ΔE(M(+)))), suggesting that substituent effect on cation-π interactions is largely additive. The ΔV(min) of C(6)H(5)X systems and additivity feature have been used to make predictions on the interaction energies of 80 multiple substituted cation-π complexes with above 97% accuracy. The average mean absolute deviation of the V(min)-predicted interaction energy, E(M(+))(V) from the calculated E(M(+)) is -0.18 kcal/mol for Li(+), -0.09 kcal/mol for Na(+), -0.43 kcal/mol for K(+), and -0.67 kcal/mol for NH(4)(+), which emphasize the predictive power of V(min) as well as the additive feature of the substituent effect.     

烷基在针状焦形成中的作用

采用煤焦油沥青的甲苯可溶物和废聚苯乙烯共碳化制备针状焦,考察了中间相沥青中烷基含量对针状焦性能的影响。结果表明,通过添加废聚苯乙烯共碳化,中间相沥青中烷基的质量分数从12.0%增加到33.3%,可以制备出热膨胀系数更低、光学各向异性排列更好的针状焦。代表光学各向异性指数的两个量,在光学结构单元中,平行于热膨胀系数方向的轴向分矢量平均长度和光学结构单元的矢量平均长度,分别从20.8μm 和23.4μm增加到28.4μm和28.8μm,热膨胀系数从0.8×10^-6 /K降低到0.1×10^-6 /K。针状焦形成过程中中间相沥青的烷基含量增加使体系黏度降低,有利于光学各向异性相的融并和定向排列。烷基的增多在固化阶段产生足量的气体,在向外逸出过程中使融并中间相的芳香平面大分子沿轴向排列的更为规整。     

Revisiting Markovnikov addition to alkenes via molecular electrostatic potential

Molecular electrostatic potentials (MESP) surrounding the pi-region of several substituted ethylenes (CH(2)CHR) have been characterized by locating the most negative-valued point (V(min)) in that region. The substituents have been classified as electron donating and withdrawing on the basis of the increase or decrease in the negative character of V(min) in these systems as compared to ethylene. The values of V(min) show a good linear correlation with the Hammett sigma(p) constants, suggesting that the substituent electronic effects in substituted ethylenes and substituted benzenes are basically similar. With electron-donating substituents, the position of MESP minimum is closer to the unsubstituted carbon facilitating the pi-complex formation of it with HCl at this site. Such a regiospecific pi-complex formation is found to favor the formation of Markovnikov-type transition state for the addition of HCl to CH(2)CHR. For the electron-withdrawing substituents, the V(min) location is almost equidistant and farther from the ethylenic carbon atoms. This and the less negative V(min) values account for the less regiospecific CH(2)CHR...HCl pi-complexes as well as the transition states for the HCl addition to CH(2)CHR when R is an electron-withdrawing group. The interaction energy (E(int)) between CH(2)CHR and HCl for the formation of the CH(2)CHR...HCl pi-complex shows a good linear correlation with the corresponding V(min) value.     

Magnetic interactions in alkyl substituted cyclohexane diradical systems: a broken symmetry approach

Magnetic interactions in alkyl substituted cyclohexane diradical systems have been investigated within the framework of spin flip density functional theory. The investigations suggest a ferromagnetic interaction for both the alkyl substituted cyclohexane-1,3-diyls and cyclohexane-1,4-diyls. However, in the case of cyclohexane-1,3-diyls, the ferromagnetic interaction is much stronger than its 1,4 analogue. Interestingly, it has been observed that this interaction is reduced to almost half the value from the butyl to the decyl substituted unit relative to the lower homologues up to the propyl substituted unit in cyclohexane-1,3-diyls. On the other hand, in case of alkyl substituted cyclohexane-1,4-diyls, the ferromagnetic interaction for the higher homologues, i.e., butyl to decyl substituted units, substantially reduces to almost 5-6 times the value of its lower homologue (methyl and ethyl substituted unit). In both these cyclohexane diradical systems, beyond butyl substituted unit, a saturation effect in the magnetic coupling constant (J) value is observed. The rapid decrease followed by a saturation in the singlet-triplet gap and J as well may be explained by considering positive inductive effect of the alkyl substituent.     

Accurate prediction of cation-π interaction energy using substituent effects

Substituent effects on cation-π interactions have been quantified using a variety of Φ-X···M(+) complexes where Φ, X, and M(+) are the π-system, substituent, and cation, respectively. The cation-π interaction energy, E(M(+)), showed a strong linear correlation with the molecular electrostatic potential (MESP) based measure of the substituent effect, ΔV(min) (the difference between the MESP minimum (V(min)) on the π-region of a substituted system and the corresponding unsubstituted system). This linear relationship is E(M(+)) = C(M(+))(ΔV(min)) + E(M(+))' where C(M(+)) is the reaction constant and E(M(+))' is the cation-π interaction energy of the unsubstituted complex. This relationship is similar to the Hammett equation and its first term yields the substituent contribution of the cation-π interaction energy. Further, a linear correlation between C(M(+))() and E(M(+))()' has been established, which facilitates the prediction of C(M(+)) for unknown cations. Thus, a prediction of E(M(+)) for any Φ-X···M(+) complex is achieved by knowing the values of E(M(+))' and ΔV(min). The generality of the equation is tested for a variety of cations (Li(+), Na(+), K(+), Mg(+), BeCl(+), MgCl(+), CaCl(+), TiCl(3)(+), CrCl(2)(+), NiCl(+), Cu(+), ZnCl(+), NH(4)(+), CH(3)NH(3)(+), N(CH(3))(4)(+), C(NH(2))(3)(+)), substituents (N(CH(3))(2), NH(2), OCH(3), CH(3), OH, H, SCH(3), SH, CCH, F, Cl, COOH, CHO, CF(3), CN, NO(2)), and a large number of π-systems. The tested systems also include multiple substituted π-systems, viz. ethylene, acetylene, hexa-1,3,5-triene, benzene, naphthalene, indole, pyrrole, phenylalanine, tryptophan, tyrosine, azulene, pyrene, [6]-cyclacene, and corannulene and found that E(M)(+) follows the additivity of substituent effects. Further, the substituent effects on cationic sandwich complexes of the type C(6)H(6)···M(+)···C(6)H(5)X have been assessed and found that E(M(+)) can be predicted with 97.7% accuracy using the values of E(M(+))' and ΔV(min). All the Φ-X···M(+) systems showed good agreement between the calculated and predicted E(M(+))() values, suggesting that the ΔV(min) approach to substituent effect is accurate and useful for predicting the interactive behavior of substituted π-systems with cations.     

Predicting reduction potentials of 1,3,6‐triphenyl fulvenes using molecular electrostatic potential analysis of substituent effects

The influence of mono‐ and multiple substituent effect on the reduction potential (E⁰) of 1,3,6‐triphenyl fulvenes is investigated using B3LYP‐SMD/6‐311+G(d,p) level density functional theory. The molecular electrostatic potential (MESP) minimum at the fulvene π‐system (V_min) and the change in MESP at any of the fulvene carbon atoms (ΔV_C) for both neutral and reduced forms are used as excellent measures of substituent effect from the para and meta positions of the 1,3 and 6‐phenyl moieties. Substitution at 6‐phenyl para position has led to significant change in E⁰ than any other positions. By applying the additivity rule of substituent effects, an equation in ΔV_C is derived to predict E⁰ for multiply substituted fulvenes. Further, E⁰ is predicted for a set of 2000 hexa‐substituted fulvene derivatives where the substituents and their positions in the system are chosen in a random way. The calculated E⁰ agreed very well with the experimental E⁰ reported by Godman et al. Predicting E⁰ solely by substituent effect offers a simple and powerful way to select suitable combinations of substituents on fulvene system for light harvesting applications. © 2018 Wiley Periodicals, Inc.     

Isotope Effects in the Solvolysis of Sterically Hindered Arenesulfonyl Chlorides

Solvent isotope effects in the ethanolysis of sterically hindered arenesulfonyl chlorides ruled out a proton transfer in the rate‐determining step and agreed with a S_N2 mechanism involving at least a second solvent molecule in the transition state (TS). The lack of a secondary kinetic isotope effect in the o‐alkyl groups allows us to disregard the possible contribution of σ–π hyperconjugation. The measured activation parameters are consistent with a S_N2 mechanism involving the participation of solvent molecules in the TS, possibly forming a cyclic TS through a chain of solvent molecules.     

Gas Chromatographic Determination of O-Ethyl S-(N,N-Diisopropylamino) Ethyl Methylphosphonothiolate and O,O-Diisopropyl S-Benzyl Phosphorothiolate as Corresponding Phosphonofluoridate and Phosphorofluoridate

Abstract

A gas chromatographic method has been reported for the determination of phosphonothiolates and phosphorothiolates as corresponding phosphonofluoridates and phosphorofluoridates after reaction with AgF. The transformation reaction procedures and the chromatographic conditions were recommended for the model compounds, O-ethyl S-(N,N-diisopropylamino)ethyl methylphosphonothiolate (MESP) and O,O-diisopropyl S-benzyl phosphorothiolate (DPSP). The results obtained have shown that the recovery is 100+4.5% for determination of MESP in the range of 1.88-8.00 μg/ml (in benzene solution) and the relative standard deviations (RSD) are less than 2.12% for MESP and DPSP at the 3.18, 6.30 and 5.48 μg/ml level.     

Theoretical study on the transition state of oxaphosphetane formation between ethylidenetriphenylphosphorane and acetaldehyde

The MNDO MO calculations were carried out for the formation of oxaphosphetanes from substituted ylides and aldehydes (Equations 2–4). It was found that the reactions proceed through a nearly planar cyclic four-membered ring transition state (TS) in all cases studied and that phenyl substitution on phosphorus has little effect on the TS geometry. This finding is not in line with the TS models that have been proposed to explain the experimentally observed cis-selectivity.     

Chair/Twist-Boat Energy Gap in Monocyclic, Conformationally Unconstrained Polyalkylcyclohexanes

A conformational search procedure (HUNTER), in combination with the MM3(92) program, was used for the exploration of the conformational hypersurface of alkyl-substituted cyclohexanes and for the calculation of their chair/twist-boat (TB) energy gap. The systems studied were conformationally unconstrained polyalkylcyclohexanes (alkyl = methyl, ethyl, isopropyl, and tert-butyl) possessing either geminal and/or vicinal arrangements of the alkyl groups, but differing in the number of alkyl substituents and in their relative disposition (i.e., cis or trans). The calculations indicate that in 1,1,3,3,5,5-hexaisopropylcyclohexane the TB is the lowest energy form. Modification of the cis,trans relationship of vicinal alkyl groups changes the chair/TB energy gap, and in the minimum energy conformation of cis,trans,trans-1,2,3,4-tetraisopropylcyclohexane (23c) and cis,syn,cis-1,2,4,5-tetraisopropylcyclohexane (31c) the cyclohexyl ring adopts a TB conformation. The tetrasubstituted systems cis,syn,cis-1,2-diisopropyl-3,4-dimethylcyclohexane (46), cis,syn,cis-1,4-diisopropyl-2,5-dimethyl-cyclohexane (47), and cis,trans,trans-1,2-diisopropyl-3,4-dimethylcyclohexane (41) are the least crowded monocyclic unconstrained cyclohexanes found in which the TB conformation is of lower energy than the chair form. The present study indicates that two methyls and two isopropyl substituents are sufficient for stabilizing the TB form of a cyclohexyl ring relative to the chair form.     

Synthesis and NMR assignment of pentacycloundecane precursors of potential pharmaceutical agents

The synthesis and complete NMR elucidation of eight novel pentacycloundecane (PCU) derivatives are reported. These compounds are precursors in the synthesis of PCU‐based anti‐tuberculosis (TB) agents and potential human immunodeficiency virus (HIV) protease inhibitors. Two‐dimensional (2D) NMR techniques were used to assign the NMR spectra for these compounds. Substitution of the cage molecule at (C‐8/11) further complicates the assignment, since some of the substituted alkyl chain groups overlap with the cage proton signals. The side chain heteroatoms also introduce a rare through‐space deshielding effect to some of the carbon atoms of the cage skeleton. Ring strain in the rigid cage skeleton appears to induce drastic electronic changes in some parts of the cage framework. This observation is more dramatic for the C‐4 methylene group of the cage diols and the cage ethers. Copyright © 2010 John Wiley & Sons, Ltd.     

Investigation of steric and electronic effects in the copper-catalysed asymmetric oxidation of sulfides

Steric and electronic effects in the copper-catalysed asymmetric oxidation of aryl benzyl, aryl alkyl and alkyl benzyl sulfides have been investigated. The presence of an aryl group directly attached to the sulfur is essential to afford sulfoxides with high enantioselectivities, with up to 97% ee for 2-naphthyl benzyl sulfoxide, the highest enantioselectivity achieved to date for copper-catalysed asymmetric sulfoxidation. In contrast, the benzyl substituent can be replaced by sterically comparable groups with no effect on enantioselectivity. Copper-mediated oxidation of substituted aryl benzyl sulfides display modest steric and electronic effects resulting in comparable or lower enantioselectivities to those obtained with the unsubstituted benzyl phenyl sulfide.     

Lone-pair orbital interactions in polythiaadamantanes

The electronic structures of a series of polythiaadamantanes from thiaadamantane through 2,4,6,8,9,10-hexathiaadamantane (HTA) have been analyzed using density functional theory calculations in conjunction with Hückel and natural bond orbital analysis. The effects of multiple sulfur p-type lone-pair orbital interactions on ionization potentials, hole mobilities, and electronic coupling have been determined. An overall increase in the average energy of the lone-pair orbitals as the number of sulfur atoms increases is predicted, with the exact positioning of the HOMO depending on specific lone-pair interactions. Separation of through-bond (TB) and through-space (TS) interactions between intramolecular sulfur atoms has been performed using localized molecular orbitals and model systems based on interacting hydrogen sulfide molecules. TB interations were found to reduce orbital splitting, while TS interactions were found to increase orbital splitting. TS interactions were more or less constant from one polythiaadamantane to the next, and the contributions of TB effects to individual orbital energies vary depending on the relative orientation of sulfur atoms as determined by the sigma molecular framework. Electronic coupling between intermolecular sulfur lone-pair orbitals was determined by investigating unique dimer pairs observed in the crystal structure of HTA. Electronic coupling is not as strong as expected given the short intermolecular S-S distances observed in the crystal structure. In general, B3LYP/6-31G(d) and B3LYP/6-311+G(d,p) give very similar orbital energies and splittings.     

Effects of a flexible alkyl chain on a ligand for CuAAC reaction

Imidazole derivatives substituted by a normal alkyl group are shown to be efficient as a ligand for the copper(Ι)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. An alkyl chain on the imidazole ligands shows an efficient steric effect and benefits the reaction. Such functionalities of an alkyl chain allow a rapid CuAAC reaction of even a bulky alkyne, which has been difficult to perform under conventional conditions.     

Study of chemoselective asymmetric hydrogenation of (1-bromo-1-alkenyl)boronic esters with iridium–PˆN complexes

In this paper we report the first chemoselective asymmetric hydrogenation of (1-bromo-1-alkenyl)boronic esters, which constitutes a new route to (α-bromoalkyl)boronic esters. The study demonstrates that excellent chemoselectivities along with full conversions can be obtained for hydrogenation of alkyl substituted derivatives with iridium–PˆN complexes. Moreover, acyclic alkyl derivatives afford (α-bromoalkyl)boronic esters in good enantioselectivities ranging from 64 to 73% ee. A cyclic alkyl derivative was obtained only in a nearly racemic form. The (1-bromo-1-alkenyl)boronic esters appear to be less reactive towards homogenous hydrogenation conditions than their chloro analogues as demonstrated by the higher catalyst loadings required to achieve full conversions for alkyl derivatives and lower conversions observed for the aryl substituted derivatives.     

Molecular electrostatic potential for exploring π-conjugation: a density-functional investigation

Molecular electrostatic potentials (MESP) of the most common building blocks of organic π-conjugated systems, viz. ethylene, acetylene, benzene, furan, pyrrole, thiophene and phenylvinylene, are examined at the B3LYP/6-311++G(2d,2p) level. The topography of MESP is employed for mapping the strength of electronic conjugation between these building blocks. When electron-rich molecular regions are connected to each other, the MESP value of the corresponding conjugation critical point (CCP) is able to provide a quantitative measure of the strength of the conjugation. The systems with stronger conjugation are generally seen to possess a larger negative value of CCP and a smaller difference (ΔV(CM-CCP)) between the MESP values of respective conjugated minimum (CM) and the CCP, in agreement with the experimental as well as other theoretical results. The present MESP topography-based approach thus offers a measure of the quantitative strength of π-conjugation in molecules.     

Formation of Quaternary Stereogenic Centers by Copper‐Catalyzed Asymmetric Conjugate Addition Reactions of Alkenylaluminums to Trisubstituted Enones

Alkenylaluminums undergo asymmetric copper‐catalyzed conjugate addition (ACA) to β‐substituted enones allowing the formation of stereogenic all‐carbon quaternary centers. Phosphinamine–copper complexes proved to be particularly active and selective compared with phosphoramidite ligands. After extensive optimization, high enantioselectivities (up to 96 % ee) were obtained for the addition of alkenylalanes to β‐substituted enones. Two strategies for the generation of the requisite alkenylaluminums were explored allowing for the introduction of aryl‐ and alkyl‐substituted alkenyl nucleophiles. Moreover, alkyl‐substituted phosphinamine (SimplePhos) ligands were identified for the first time as highly efficient ligands for the Cu‐catalyzed ACA.     

Molecular electrostatic potential studies on antiepileptic drug: Troxidone

Ab initio SCF -MO -LCAO calculations of the molecular electrostatic potential (MEP ) have been carried out on a seven-member series related to the antiepileptic drug troxidone. The effect of the substituted alkyl groups on the bioactivity of these molecules is discussed. The substituted alkyl groups increase the negative potential found near the oxygen atoms in the molecular plane.     

Orientation in metal ammonia reductions

The unique orientation effects observed in the alkali metal-ammonia reactions of aromatic compounds are considered from a molecular orbital viewpoint. The Birch rule governing the reduction of substituted aromatics, the peculiar effect of substituents on the ease of hydrogenolysis of benzyl alcohols, the similar effect in the dealkylation and dearylation of alkyl aryl ethers and aryl ethers, the course of dealkoxylation of alkyl aryl ethers, are all found to be reasonably accommodated by molecular orbital theory.     

A DFT study of H-isomerisation in alkoxy-, alkylperoxy- and alkyl radicals: Some implications for radical chain reactions in polymer systems

Intramolecular 1-n H-shift (n = 2, 3… 7) reactions in alkoxy, alkyl and peroxy radicals were studied by density functional theory (DFT) at the B3LYP/6-311+G∗∗ level and compared with respective intermolecular H-transfers. It was found that starting from 1 to 3 H-shift the barrier heights stepwise decrease with increasing n reaching minimum for 1-5 and 1-6 H-shifts. This dependence can be ascribed to the decrease of the strain with increasing transition state (TS) ring size, which is minimal in six- and seven-member rings. The barrier heights of H-shifts in alkyl radicals are systematically larger than those in alkoxy radicals: the respective activation energies (E_a) of 1-5 and 1-6 H-shifts are about 59-67 kJ/mol for alkyl radical and 21-34 kJ/mol for alkoxy radicals. Further increase of the TS ring size in 1-7 H-shifts leads to the increase of the barrier to 44 kJ/mol in the hexyloxy radical and 84 kJ/mol for n-heptyl radical. We have also found that intermolecular H-transfer reactions in all three types of free radicals have smaller barriers than respective intramolecular 1-5 or 1-6 H-shifts by 4-25 kJ/mol. The mentioned difference can be explained in terms of enhanced nonbonding repulsion interaction in the cyclic TS structures compared to respective intermolecular TS. B3LYP/6-311+G∗∗ geometric parameters and imaginary frequencies for 1-n H-shifts TS are consistent with respective calculated barrier heights. Reactivity of some other radicals compared to alkoxy, peroxy and alkyl radicals as well as other factors influencing their reactivity (π-conjugation, steric effect and ring strain in cyclic TS, etc.) are also briefly discussed in relation to free radical reactions in polymer systems.