Physical Organic Research Articles

John D. Roberts (1918–2016)

John D. (Jack) Roberts, Institute Professor of Chemistry Emeritus at the California Institute of Technology died on October 29, 2016, at the age of 98. Roberts was one of the of the iconic figures in physical organic chemistry of the 20th century. His achievements included proving the occurrence of benzynes and nonclassical carbocations as reaction intermediates, and he was instrumental in establishing NMR spectroscopy as a standard analytical technique in organic chemistry.

John D. Roberts (1918–2016)

John D. (Jack) Roberts, Institute Professor of Chemistry Emeritus at the California Institute of Technology died on October 29, 2016, at the age of 98. Roberts was one of the of the iconic figures in physical organic chemistry of the 20th century. His achievements included proving the occurrence of benzynes and nonclassical carbocations as reaction intermediates, and he was instrumental in establishing NMR spectroscopy as a standard analytical technique in organic chemistry.

Adventures in Reactive Intermediate Chemistry: A Perspective and Retrospective.

I review aspects of my research on reactive intermediates, specifically the physical organic chemistry of carbenes and carbocations. The topics treated include carbenoids, carbenic philicity, absolute rates of carbene/alkene additions, the diazirine exchange reaction and derived carbenes, carbene equilibria, carbocations from diazotates, and carbocations from alkoxychlorocarbenes. The essay concludes with observations on the protean nature of physical organic chemistry.

Profile: Early Excellence in Physical Organic Chemistry

Profile: Early Excellence in Physical Organic Chemistry

Exploring the Gas Phase Synthesis of the Elusive Class of Boronyls and the Mechanism of Boronyl Radical Reactions under Single Collision Conditions.

Until recently, the chemistry of boronyl (BO), a diatomic radical isolectronic with the cyano (CN) species, has remained unknown. The boronyl group is characterized by a boron-oxygen multiple bond, and because of the inherent electron deficiency of the boron atom, boronyls (RBO) are highly reactive and typically only exist in their cyclotrimeric form (RBO)3. Due to their invaluable role as reactants, the isolation of the monomers in gas phase experiments has been extensively sought after by the organic synthesis and physical organic chemistry communities but never achieved. Besides the interests from a physical organic and synthetic point of view, boronyls also play a role as reaction intermediates in boron-assisted rocket propulsion systems. In this Account, we review recent experimental work in which gas phase organo boronyl monomers (RBO) are formed via bimolecular reactions of the boronyl radical (BO) with C2-C6 unsaturated hydrocarbons. The investigated hydrocarbons are widely exploited as fuels, and their reactions with boronyl radicals under single collision conditions lead to the formation of organo boronyls. Our studies also elucidate the mechanisms of their formation reactions thus furnishing a comprehension at the molecular level of this reaction class. The variety of the employed hydrocarbon substrates has allowed us to systematically classify the chemical behavior of the boronyl radicals. With the exception of the case of the dimethylacetylene reaction, the boron monoxide radical versus atomic hydrogen exchange mechanisms were always open leading to the formation of highly unsaturated organo boronyl monomers (RBO), which could be easily identified because they cannot trimerize under single collision conditions. Besides the hydrogen displacement pathway, methylacetylene, dimethylacetylene, and propylene, carrying one or two methyl groups, were also found to eliminate a methyl group. In all systems, the reactions were barrierless, indirect, and initiated by addition of the boron monoxide radical to the π electron density of the hydrocarbon molecule, with the radical center located at the boron atom of the BO radical, thus leading to doublet radical intermediates. These intermediates either decompose via hydrogen or methyl loss or isomerize prior to their decomposition via atomic hydrogen or migration of the BO moiety. A consistent trend suggests that all exit transition states are rather tight with those involved in the hydrogen atom loss depicting exit barriers of typically 25 to 35 kJ mol-1, whereas the methyl loss pathways are associated with tighter exit transition states located about 30-50 kJ mol-1 above the separated products. Further, the overall energetics suggest that those bimolecular reactions are exoergic by 40-90 kJ mol-1. These findings confirm that this reaction class leads to the formation of highly unsaturated organo boronyl molecules.

Control and Switching of Aromaticity in Various All-Aza-Expanded Porphyrins: Spectroscopic and Theoretical Analyses.

Modification of aromaticity is regarded as one of the most interesting and important research topics in the field of physical organic chemistry. Particularly, porphyrins and their analogues (porphyrinoids) are attractive molecules for exploring various types of aromaticity because most porphyrinoids exhibit circular conjugation pathways in their macrocyclic rings with various molecular structures. Aromaticity in porphyrinoids is significantly affected by structural modification, redox chemistry, NH tautomerization, and electronic states (singlet and triplet excited states). Conversely, aromaticity significantly affects the spectroscopic properties and chemical reactivities of porphyrinoids. In this context, considerable efforts have been devoted to understanding and controlling the aromaticity and antiaromaticity of porphyrinoids. Thus, a series of porphyrinoids are in the limelight, being expected to shed light on this field because they have some advantages to demonstrate the switching of aromaticity; it is possible to control the aromaticity by lowering the temperature, adding and removing the protons of expanded porphyrins, changing the chemical environment, and switching the electronic states (triplet and singlet excited states) by photoexcitation. In this regard, this Review describes the control of aromaticity in various expanded porphyrins from the spectroscopic point of view with assistance from theoretical calculations.

Heterolytic (2 e) vs Homolytic (1 e) Oxidation Reactivity: N-H versus C-H Switch in the Oxidation of Lactams by Dioxirans.

Dioxiranes are powerful oxidants that can act via two different mechanisms: 1) homolytic (H abstraction and oxygen rebound) and 2) heterolytic (electrophilic oxidation). So far, it has been reported that the nature of the substrate dictates the reaction mode independently from the dioxirane employed. Herein, we report an unprecedented case in which the nature of the dioxirane rules the oxidation chemoselectivity. In particular, a switch from C-H to N-H oxidation is observed in the oxidation of lactams moving from dimethyl dioxirane (DDO) to methyl(trifluoromethyl)dioxirane (TFDO). A physical organic chemistry study, which combines the oxidation with two other dioxiranes methyl(fluoromethyl)dioxirane, MFDO, and methyl(difluoromethyl)dioxirane, DFDO, with computational studies, points to a diverse ability of the dioxiranes to either stabilize the homo or the heterolytic pathway.

Advances in Soft Functional Materials Research

Advances in Soft Functional Materials Research

Guest Editorial, Petr Zuman 90th Birthday Issue

Guest Editorial, Petr Zuman 90th Birthday Issue

Profile: Early Excellence in Physical Organic Chemistry

Profile: Early Excellence in Physical Organic Chemistry

Physical Organic Chemistry: new Latin American Conference at Villa Carlos Paz, Córdoba, Argentina, 2015

Physical Organic Chemistry: new Latin American Conference at Villa Carlos Paz, Córdoba, Argentina, 2015

The Fluorine Gauche Effect: A Brief History

AbstractTransforming the fluorine gauche effect from an academic curiosity into a powerful acyclic conformational control strategy has enriched molecular design. This expansive approach to modulating structure has proven to be particularly valuable in the construction of functional small molecules, thereby finding application in diverse disciplines, ranging from therapeutic medicine to enantioselective catalysis. In contrast to the well‐established arsenal of conformational control tactics, in which conformer populations result from minimising nonbonding interactions, (e.g., A1,3‐ or A1,2‐strain), the fluorine gauche effect is attributable to stabilising interactions comprised of two components: stereoelectronic and electrostatic. Conformer populations are partially determined by favourable, hyperconjugative interactions involving proximal electron‐rich σ‐bonds, π‐systems, and nonbonding electron pairs with the antibonding orbital of the C−F σ‐bond: σ→σ*, π→σ*, and n→σ*, respectively. Electrostatic, charge‐dipole interactions (e.g., N+⋅⋅⋅Fδ−) also play a crucial role in stabilising what are often counter‐intuitive conformations. These noncovalent interactions, permissible on account of the low van der Waals radius and high electronegativity of the fluorine atom, render this effect fundamentally important and practically valuable in structural chemistry. In this contribution to the Rosarium Philosophorum in honour of Prof. Jack David Dunitz FRS, we endeavour to delineate, albeit in an abridged form, the evolution of the fluorine gauche effect from a fundamental spectroscopic study to a ubiquitous component of physical organic chemistry.

Profile: Early Excellence in Physical Organic Chemistry

Profile: Early Excellence in Physical Organic Chemistry

Minding the Gap: Synthetic Strategies for Tuning the Energy Gap in Conjugated Molecules

While structure–property relationships are commonly developed in applications of physical organic chemistry to real-world problems at the graduate level, they have not been generally emphasized in the undergraduate chemistry curriculum. For instance, the ability to modify the energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) in π-conjugated small molecules and polymers is of particular interest in the fields of polymer chemistry and materials science, where small-gap systems can function as semiconductors in electronic devices. In order to demonstrate a general strategy for tuning the HOMO–LUMO energy gap for π-conjugated materials, a new experiment was designed for the undergraduate organic laboratory course that combines synthesis with theoretical calculations for π-conjugated biphenyl systems with differing electronic properties to generate a simple structure–property study of functional group substitution on the biphenyl core. The synth...

Chemical applicability domain of the Local Lymph Node Assay (LLNA) for skin sensitisation potency. Part 2. The biological variability of the murine Local Lymph Node Assay (LLNA) for skin sensitisation

The Local Lymph Node Assay (LLNA) is the most common in vivo regulatory toxicology test for skin sensitisation, quantifying potency as the EC3, the concentration of chemical giving a threefold increase in thymidine uptake in the local lymph node. Existing LLNA data can, along with clinical data, provide useful comparator information on the potency of sensitisers. Understanding of the biological variability of data from LLNA studies is important for those developing non-animal based risk assessment approaches for skin allergy. Here an existing set of 94 EC3 values for 12 chemicals, all tested at least three times in the same vehicle have been analysed by calculating standard deviations (SD) for logEC3 values. The SDs range from 0.08 to 0.22. The overall SD for the 94 logEC3 values is 0.147. Thus the 95% confidence limits (2xSD) for LLNA EC3 values are within a factor of 2, comparable to those for physico-chemical measurements such as partition coefficients and solubility. The residual SDs of Quantitative Mechanistic Models (QMMs) based on physical organic chemistry parameters are similar to the overall SD of the LLNA, indicating that QMMs of this type are unlikely to be bettered for predictive accuracy.

Chemical applicability domain of the Local Lymph Node Assay (LLNA) for skin sensitization potency. Part 1. Underlying physical organic chemistry principles and the extent to which they are represented in the LLNA validation dataset

• Chemical mechanisms of skin sensitization are reviewed. • In vivo test methods including the LLNA are discussed. • Ranges of key physico-chemical parameters are extracted to characterise one type of applicability domain for the LLNA.

PROFILE: Early Excellence in Physical Organic Chemistry

PROFILE: Early Excellence in <i>Physical Organic Chemistry</i>

Analyzing the substitution effect on the CoMFA results within the framework of density functional theory (DFT)

Though QSAR was originally developed in the context of physical organic chemistry, it has been applied very extensively to chemicals (drugs) which act on biological systems, in this idea one of the most important QSAR methods is the 3D QSAR model. However, due to the complexity of understanding the results it is necessary to postulate new methodologies to highlight their physical-chemical meaning. In this sense, this work postulates new insights to understand the CoMFA results using molecular quantum similarity and chemical reactivity descriptors within the framework of density functional theory. To obtain these insights a simple theoretical scheme involving quantum similarity (overlap, coulomb operators, their euclidean distances) and chemical reactivity descriptors such as chemical potential (μ), hardness (ɳ), softness (S), electrophilicity (ω), and the Fukui functions, was used to understand the substitution effect. In this sense, this methodology can be applied to analyze the biological activity and the stabilization process in the non-covalent interactions on a particular molecular set taking a reference compound.

Optimizing the Interactions of Surfactants with Graphitic Surfaces and Clathrate Hydrates.

Surfactants are amphiphilic molecules active at the surface/interface and able to self-assemble. Because of these properties, surfactants have been extensively used as detergents, emulsifiers, foaming agents, and wetting agents. New perspectives have been opened by the exploitation of surfactants for their capacity to interact as well with simple molecules or surfaces. This feature article gives an overview of significant contributions in the panorama of the current research on surfactants, partly accomplished as well by our research group. We look at several recent applications (e.g., adsorption to graphitic surfaces and interactions with hydrate crystals) with the eye of physical organic chemists. We demonstrate that, from the detailed investigation of the forces involved in the interactions with hydrophobic surfaces, it is possible to optimize the design of the surfactant that is able to form a stable and unbundled carbon nanotube dispersion as well as the best exfoliating agent for graphitic surfaces. By studying the effect of different surfactants on the capacity to favor or disfavor the formation of a gas hydrate, it is possible to highlight the main features that a surfactant should possess in order to be devoted to that specific application.

Profile: early excellence in physical organic chemistry

Profile: early excellence in physical organic chemistry