The alkyl group is a –I + R substituent

Electronic substituent effects are usually classified as inductive (through s-bonds) and resonance effects (via p-bonds). The alkyl group has been usually regarded as a s-electron donor substituent (+I effect, according to the Ingold''s classification). However, a s-withdrawing, p-donor effect (–I + R pattern) allows explaining the actual electron-withdrawing behavior of alkyl groups when bound to sp3 carbon atoms as well as their well-known electron-releasing properties when attached to sp2 or sp atoms. Alkyl substitution effects on several molecular properties (dipole moments, NMR, IR, and UV spectra, reactivity in gas phase and solution) are discussed. Los efectos electrónicos del sustituyente se clasifican habitualmente como inductivos (a través de enlaces s) o de resonancia (mediante enlaces p). El grupo alquilo ha sido considerado habitualmente como un sustituyente dador de densidad electrónica s (+I, según la clasificación de Ingold). Sin embargo, un patrón s-aceptor p-dador (–I + R) permite explicar el comportamiento real de los grupos alquilo como atractores de electrones cuando están unidos a átomos de carbono sp3, así como sus conocidas propiedades dadoras de electrones cuando están unidos a átomos sp2 o sp. Se discuten los efectos de sustitución del grupo alquilo en varias propiedades moleculares (momentos dipolares, espectros de RMN, IR y UV, reactividad en fase gas y disolución)

The synthesis and chemistry of Quinolino(7,8-h)quinoline derivatives : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Chemistry at Massey University, Manawatu, New Zealand

Proton sponges are a class of neutral organic superbases. Quinolino[7,8-h]quinoline (QQ) is one such molecule. Structurally it has two closely positioned nitrogen atoms which cause a destabilising lone electron overlap which manifests as a helical torsional twist that can be relieved by monoprotonation or complexation. These compounds are highly basic and are chelators that can accommodate a variety of ion sizes. Exploration of the structural properties of QQ provides an avenue for non-symmetric compound synthesis. Research interest arose in developing original synthetic pathways and exploring the chemistry of this QQ moiety, and its potential uses. This work primarily focussed on the development of methods towards new derivatives containing the QQ core structure, of which several were developed. Exploration of their properties as bases was begun in the context of both experimental measurements and theoretical calculations, allowing some to be classified as superbases. Computational analysis also gave insight into structural changes taking place during the protonation process. Potential uses of QQ derivatives as chelators for metals were examined. An X-ray crystal structure of a beryllium containing 4,9-dihydroxyquinolino[7,8-h]quinoline was achieved, the 7th reported ion to be chelated by a QQ compound

Stereoelectronics of Carboxylate-Imidazolium Hydrogen Bonds in Models of the Aspartate-Histidine Couple in Serine Proteases.

The geometry of the carboxylate-imidazolium hydrogen bond in the crystalline state and the effect of microenvironment are investigated in models of the aspartate-histidine (Asp-His) couple. Synthetic methods leading to the preparation of intramolecular models, possessing syn and anti-oriented hydrogen bonds, also are described. A single-pot procedure has been developed for converting phenoxyacetonitriles into their respective benzimidazole derivative in higher yields than the traditional two step procedure. An efficient single-pot procedure also has been developed for converting benzofuran to its acetylene derivative, 2-acetoxyphenylacetylene. This method involves in situ acetylation of the unstable phenol intermediate. Nine intermolecular imidazolium-benzoate couples have been prepared and their structures analyzed by single crystal X-ray crystallography. The structure of an intramolecular model also has been determined by single crystal X-ray crystallography. The orientation of all the imidazolium hydrogen bonds is syn relative to the carboxylate. Furthermore, syn hydrogen bonds are shorter than anti hydrogen bonds. The strength of the hydrogen bond increases as $\Delta$pK\sb{\rm a} between the donor and acceptor decreases. The basicity of the carboxylate is governed by the number of hydrogen bonds accepted by it: successive hydrogen bonding to carboxylate decreases its basicity. Consequently, correlations of hydrogen-bond strength and basicity (pK\sb{a} and PA) of carboxylates are more reliable when carboxylates accept equal number of hydrogen bonds. Stereoelectronics of syn hydrogen bonding to carboxylates are affected by the presence of strong and geometrically constrained anti hydrogen bonding. With respect to the plane of the carboxylate, syn hydrogen bonding lies (1) within 10\sp\circ in the absence of anti hydrogen bonding, (2) out-of-plane (30-35\sp\circ) in the presence of one anti hydrogen bond, and (3) within 10\sp\circ in the presence of two anti hydrogen bonds. Out-of-plane distortion in the presence of an anti-oriented hydrogen bond suggests a catalytic role for the anti-oriented Ser-214 side-chain in serine proteases

Inducing a pH-dependent conformational response by competitive binding to Zn2+ of a series of chiral ligands of disparate basicity

Molecules that change shape in response to environmental conditions are central to biological molecular communication devices and their synthetic chemical analogues. Here we report a molecular system in which a series of chiral anionic ligands of differing basicity are selectively protonated according to the pH of the medium. A cationic circular dichroism (CD) reporter complex responds to anion binding by selecting one of two alternative enantiomeric conformations. Exploiting the principle that less basic anions have, in general, weaker electrostatic interactions than more basic anions, a set of three chiral acids with large (>5 unit) pK(a) differences and differing configurations were sequentially deprotonated in acetonitrile by addition of base, allowing the most basic anion in the mixture at any time to bind to the reporter complex. A characteristic CD output resulted, which changed in sign as the next-most basic anion was revealed by the next deprotonation in the series. Four cycles of switching between three ligand-bound states were achieved with minimal changes in signal magnitude, by alternating addition of base and acid. The pH-dependent conformational response was used to transduce a signal by appending to the binding site a 2-aminoisobutyric acid (Aib) oligomer, whose M or P helical conformation depended on the chirality of the bound ligand, and was reported by a remote (13)C-labelled NMR reporter group. The multicomponent system thus converts a pH signal into a programmable conformational response which induces a remote spectroscopic effect

Design of Alcohol Substitution and Higher-Order Superbases with Cyclopropenium Ions

This thesis employs cyclopropenium ions as central design elements in a novel catalytic nucleophilic substitution of alcohols and in the preparation and study of a number of extremely strong organic bases. The first chapter describes the use of diphenylcyclopropenone as a catalyst for the substitution of a range of alcohols with sulfonic acids that proceeds with inversion of stereochemistry. The other reagents needed are methanesulfonic anhydride and a simple amine base. The process relies on the concept of cyclopropenium activation developed by the Lambert group. The catalyst is the only material not removed from the product by aqueous workup, and a protocol for its conversion into a water-soluble derivative is outlined. A stoichiometric procedure for more sterically demanding substrates is also detailed. The second chapter outlines the preparation of six new classes of higher-order superbases by novel and robust methods. Five members incorporate the cyclopropenimine function, a superbase recently introduced by the Lambert group. Systematic structure-basicity relationships reveal fundamental electronic properties of guanidines, phosphazenes, and cyclopropenimines. Molecular structures show a number of organizational elements that could assist in the design of next-generation higher-order superbases. Predictive effects of structure on both stability and selectivity between Brønsted basic and nucleophilic behavior are explained. Finally, the first direct neutral Brønsted base catalysis of the relatively non-acidic α-aryl ester pronucleophile class is described, alluding to the increased number of useful and widely available types of starting materials that can be engaged directly by this reaction mode