Tetronamides as latent acyclic vinylogous amides in formal aza-[3 + 3] cycloaddition reactions with alpha,beta-unsaturated iminium salts. An unexpected rearrangement and an approach to synthesis of substituted piperidines

A detailed account regarding formal aza-[3 + 3] cycloaddition reactions of tetronamides with alpha,beta-unsaturated iminium salts is described here. This investigation uncovers regioisomeric cycloadducts that were not found in previous studies involving this formal cycloaddition and an unexpected rearrangement that led to pyridines and dihydropyridines. Both stereochemical and regiochemical issues raised in this study provide further mechanistic insights into this cycloaddition. With careful control of reaction temperatures, the desired formal cycloadducts are obtained. Ensuing transformation of these cycloadducts into functionalized piperidines establishes the concept of employing tetronamides as latent acyclic vinylogous amides for the formal aza-[3 + 3] cycloaddition.     

General formula to calculate formal unsaturation of chemical compounds

Based on graph theory fundamentals, a general formula to calculate formal unsaturation of chemical compounds that contain atoms of any valence is deduced, and the mathematical meaning of this widely used chemical concept is shown.     

CHEMLEARN: microcomputer-based training for CHEMLINE, an alternative to formal classroom training

CHEMLINE (CHEMical Dictionary OnLINE), the National Library of Medicine's online chemical dictionary file, is primarily used by librarians and information scientists to enhance the retrieval of bibliographic information associated with chemical substances. This paper will discuss CHEMLEARN, a microcomputer-based training program designed to provide inexpensive, easily accessible self-instruction as an alternative to formal classroom training in the use of CHEMLINE. CHEMLEARN allows novice users to learn at their own pace and with considerable program feedback. In addition, it provides the skilled searcher with a way to reinforce or recall previously learned search techniques without incurring online charges. CHEMLEARN may be used in place of formal training or as a precursor to or a refresher following formal training.     

On the relation between a common gauge origin formulation and the GIAO formulation of the NMR shielding tensor

In this article the formal equivalence between the “gauge including atomic orbitals” (GIAO) and the simpler common gauge (cg) formulations of the nuclear magnetic resonance (NMR) shielding tensor is proven. To be able to give this proof, one has to assume exactly solved zeroth order quantum mechanical equations and complete basis sets. The proof of the equivalence has been known in the literature for some time (e.g. S.T. Epstein `The variation method in quantum chemistry', Academic Press, 1974). However, our approach has the advantage that, by comparing the GIAO and cg methods, it provides insight into the para- and diamagnetic contributions of the shielding. Thus, it yields justification for qualitative analysis schemes that have been used to explain trends in chemical shifts. Our formal proof is based on density functional theory. However, it is argued that very similar arguments should apply to other levels of theory as well. Received: 25 June 2002 / Accepted: 18 July 2002 / Published online: 15 October 2002 Acknowledgments. The author would like to acknowledge Tom Ziegler, Calgary, for numerous discussions on the subject. The reviewer is acknowledged for the insightful and detailed comments. Correspondence to: G. Schreckenbach e-mail: schrecke@alcor.concordia.ca     

Molecular beams and chemical dynamics at surfaces

The use of molecular beams to study chemical dynamics at surfaces is outlined. The techniques is briefly introduced and its applications are given in a few areas. Scattering experiments give detailed information about the first steps toward a chemical reaction at a surface. Beams with enhanced population of specific quantum states make an even more detailed analysis possible. Adsorption at surfaces can be studied very well using beam methods, especially in the case of activated processes. Beams can be used to grow novel structures. Beams allow the study of chemical reactions at surfaces, and in particular those where product are directly ejected into the gas phase, or where reactions take place upon impact. Finally the study of liquid surfaces is briefly introduced.     

Synthesis of endotoxic principle of bacterial lipopolysaccharide and its recognition by the innate immune systems of hosts

A new stage of endotoxin research was brought about by structure elucidation and chemical synthesis of lipid A, the lipophilic partial structure of the lipopolysaccharide (LPS) of Gram-negative bacteria. Synthetic lipid A exhibited full endotoxic activity, which gave unequivocal evidence for the concept that lipid A is the active entity of endotoxin. Various lipid A analogues, as well as their radiolabeled derivatives and more complex partial structures of LPS, were also synthesized. By the use of these synthetic homogeneous preparations, not only simple studies on structure-activity relationships but precise and detailed analyses became possible on how this typical bacterial component is recognized by the innate immune receptor complex of mammalian cells.     

Computer-Assisted Solution of Chemical Problems—The Historical Development and the Present State of the Art of a New Discipline of Chemistry

The topic of this article is the development and the present state of the art of computer chemistry, the computer-assisted solution of chemical problems. Initially the problems in computer chemistry were confined to structure elucidation on the basis of spectroscopic data, then programs for synthesis design based on libraries of reaction data for relatively narrow classes of target compounds were developed, and now computer programs for the solution of a great variety of chemical problems are available or are under development. Previously it was an achievement when any solution of a chemical problem could be generated by computer assistance. Today, the main task is the efficient, transparent, and non-arbitrary selection of meaningful results from the immense set of potential solutions—that also may contain innovative proposals. Chemistry has two aspects, constitutional chemistry and stereochemistry, which are interrelated, but still require different approaches. As a result, about twenty years ago, an algebraic model of the logical structure of chemistry was presented that consisted of two parts: the constitution-oriented algebra of be- and r-matrices, and the theory of the stereochemistry of the chemical identity group. New chemical definitions, concepts, and perspectives are characteristic of this logic-oriented model, as well as the direct mathematical representation of chemical processes. This model enables the implementation of formal reaction generators that can produce conceivable solutions to chemical problems—including unprecedented solutions—without detailed empirical chemical information. New formal selection procedures for computer-generated chemical information are also possible through the above model. It is expedient to combine these with interactive methods of selection. In this review, the Munich project is presented and discussed in detail. It encompasses the further development and implementation of the mathematical model of the logical structure of chemistry as well as the experimental verification of the computer-generated results. The article concludes with a review of new reactions, reagents, and reaction mechanisms that have been found with the PC-programs IGOR and RAIN.     

Evaluation of canonical and microcanonical nonadiabatic reaction rate constants by using the Zhu-Nakamura formulas

We consider a problem of calculating both thermal and microcanonical rate constants for nonadiabatic chemical reactions. Instead of using the conventional transition state theory, we use a generalized seam surface and introduce a concept of a coordinate dependent effective nonadiabatic transition probability based on the Zhu-Nakamura theory which can treat the nonadiabatic tunneling properly. The present approach can be combined with Monte Carlo method so as to be applicable to chemical reactions in complicated systems. The method is demonstrated to work well in wide energy and temperature range. Numerical tests also show that it is very essential for accurate evaluation of the thermal rate constant to use the generalized seam surface and take into account the nonadiabatic tunneling effect.     

Recurrent approximation of densities and refractive indices of the homologs of different series

The mathematic relations used in chemistry describe the processes with participation of various substances and the variations in the properties of chemical compounds. For the problems of the second type especially widely appearing in organic chemistry, introduction of concept of the chemical domains of definition of such relations, i.e. the scope of molecular structures in the domain for which application of these relations provides the maximum accuracy of obtained estimates, is expedient. By examples of some physical and chemical constants, including chromatography retention indices it, is shown that increase in the accuracy of the calculation equations can be reached not due to their complication, but by ascertaining definition of the chemical domains of their application. On the other hand, examples are demonstrated where the variation in the chemical domains of definition while the equations themselves remain unchanged open principally new opportunities of their application. Unlike mathematic domains of definition, their chemical equivalents cannot be revealed by the formal analysis of mathematic formulas. Solution of such problems, as a rule, requires computational checking of their applicability for compounds belonging to various groups.     

Surface‐Assisted Cyclodehydrogenation; Break the Symmetry,Enhance the Selectivity

Selectivity in chemical reactions is a major objective in industrial processes to minimize spurious byproducts and to save scarce resources. In homogeneous catalysis the most important factor which determines selectivity is structural symmetry. However, a transfer of the symmetry concept to heterogeneous catalysis still requires a detailed comprehension of the underlying processes. Here, we investigate a ring‐closing reaction in surface‐confined meso‐substituted porphyrin molecules by scanning tunneling microscopy, temperature‐programmed desorption, and computational modeling. The identification of reaction intermediates enables us to analyze the reaction pathway and to conclude that the symmetry of the porphyrin core is of pivotal importance regarding product yields.     

Communic acids: occurrence, properties and use as chirons for the synthesis of bioactive compounds

Communic acids are diterpenes with labdane skeletons found in many plant species, mainly conifers, predominating in the genus Juniperus (fam. Cupresaceae). In this review we briefly describe their distribution and different biological activities (anti- bacterial, antitumoral, hypolipidemic, relaxing smooth muscle, etc.). This paper also includes a detailed explanation of their use as chiral building blocks for the synthesis of bioactive natural products. Among other uses, communic acids have proven useful as chirons for the synthesis of quassinoids (formal), abietane antioxidants, ambrox and other perfume fixatives, podolactone herbicides, etc., featuring shorter and more efficient processes.     

Thermal,three-carbon + two-atom cycloaddition of cyclopropenone ketals with carbon-heteroatom double bonds: Butenolide,furan, and γ-keto ester preparation.

A preliminary study of the thermal reaction of cyclopropenone ketals with carbon-heteroatom double bonds is detailed. The reaction with aldehyde and keto carbonyls provide butenolide ortho esters, the product of a formal three-carbon + two-atom cycloaddition of the cyclopropenone ketal across the carbon-oxygen double bond.     

Automatic kinetic model generation and selection based on concentration versus time curves

The goal of the paper is to automatize the construction and parameterization of kinetic reaction mechanisms that can describe a set of experimentally measured concentration versus time curves. Using the framework and theorems of formal reaction kinetics, first, we build a set of possible mechanisms with a given number of measured and unmeasured (real or fictitious) species and reaction steps that fulfill some chemically reasonable requirements. Then we fit all the corresponding mass-action kinetic models and offer the best one to the chemist to help explain the underlying chemical phenomenon or to use it for predictions. We demonstrate the use of the method via two simple examples: on an artificial, simulated set of data and on a small real-life data set. The method can also be used to do a kind of lumping to generate a model that can reproduce the simulation results of a detailed mechanism with less species and thereby can largely accelerate spatially inhomogeneous simulations.     

Analysis of corrosion processes at the surface of diamond-like carbon protected zinc selenide waveguides

A detailed surface analytical study on the corrosion behavior of unprotected and diamond-like carbon (DLC)-coated mid-infrared (MIR) waveguides used in remote sensing applications at strongly oxidizing conditions is presented. High-quality DLC films, with a thickness of 100 nm serving as MIR-transparent corrosion barrier, have been produced at the surface of zinc selenide (ZnSe) attenuated total reflection waveguides via pulsed laser deposition techniques. IR microscopy and atomic force microscopy are applied to investigate the chemical inertness of DLC-based membranes against aqueous solutions of hydrogen peroxide. These stability studies show that uncoated ZnSe waveguides are subject to severe chemical surface modifications, while DLC-protected waveguides maintain their optical properties and chemical integrity. In situ studies on the corrosion behavior by a recently developed approach combining scanning electrochemical microscopy (SECM) with Au/Hg amalgam ultramicroelectrodes in a scanning stripping voltammetry experiment provides additional insight into the mechanisms of the corrosion process. It is demonstrated that the combination of surface analytical techniques and, in particular, the innovative application of SECM with amalgam electrodes provides superior information on corrosion processes at the surface of optical waveguides. This detailed study confirms the efficiency of protective DLC coatings deposited onto IR-transparent optical waveguides, rendering this novel concept ideal for sensing applications in harsh environments.     

On Electrostatics,Covalency, and Chemical Dashes: Physical Interactions versus Chemical Bonds

The increasing availability of real-space interaction energies between quantum atoms or fragments that provide a chemically intuitive decomposition of intrinsic bond energies into electrostatic and covalent terms [see, for instance, Chem. Eur. J. 2018 , 24, 9101] provides evidence for differences between the physicist's concept of interaction and the chemist's concept of a bond. Herein, it is argued that, for the former, all types of interactions are treated equally, whereas, for the latter, only the covalent short-range interactions have actually been used to build intuition about chemical graphs and chemical bonds. This has led to the bonding role of long-range Coulombic terms in molecular chemistry being overlooked. Simultaneously, blind consideration of electrostatic terms in chemical bonding parlance may lead to confusion. The relationship between these concepts is examined herein, and some notes of caution on how to merge them are proposed.     

Oxidative Prins-pinacol tandem process mediated by a hypervalent iodine reagent: scope, limitations, and applications

An oxidative Prins-pinacol tandem process mediated by a hypervalent iodine reagent has been developed. This oxidative version of the famous tandem process fits within the concept of "aromatic ring umpolung" and allows the stereoselective transformation of simple phenols into highly elaborated spirocyclic dienone cores containing several quaternary carbon centers. The scope and the limitations of this process, including the study of its stereoselectivity, are described in this article. As a direct application of this stereoselective process, we describe the formal synthesis of (-)-platensimycin, an important antibiotic agent.     

Synthesis and chemical characterisation of target identification reagents based on an inhibitor of human cell invasion by the parasite Toxoplasma gondii

The use of phenotype-based screens as an approach for identifying novel small molecule tools is reliant on successful protein target identification strategies. Here we report on the synthesis and chemical characterisation of a novel reagent for protein target identification based on a small molecule inhibitor of human cell invasion by the parasite Toxoplasma gondii. A detailed (1)H NMR study and biological testing confirmed that incorporation of an amino-containing functional group into the aryl ring of this inhibitor was possible without loss of biological activity. Interesting chemical reactivity differences were identified resulting from incorporation of the new substituent. The amine functionality was then used to prepare a biotinylated reagent that is central to our current protein target identification studies with this inhibitor.     

Structured system in chemistry: comparison with mechanics and biology

The fundamental concept of structured chemical system has been introduced and analysed in this paper. This concept, as in biology but not in physics, is very important in chemistry. In fact, the main chemical concepts (molecule and compound) have been identified as systemic concepts and their use in chemical explanation can only be justified in this approach. The fundamental concept of “environment” has been considered and then the system concept in mechanics, chemistry and biology. The differences and the analogies between the use of the systemic approach in these disciplines have been analyzed and correlated to the general problem of reductionism and complexity perspectives. The inanimate–animate dichotomy can be reconsidered in this new approach. Since the chemical systemic concepts of molecule and compound can be dated to the nineteenth century, chemistry can be considered the first true systemic science and its historical evolution can be a model for other sciences (such as the humanities) where the systemic concepts are important.     

Theoretical investigation of the sulphur K-LL auger energies and chemical shifts in a series of sulphur compounds

Two series of investigations are reported on LL double-hole states of molecules containing sulphur. First the results on the LL double ionization potentials and K-LL Auger energies of H₂S and SO₂ show that the use of a frozen-orbital approximation is preferable to SCF methods for calculation of chemical shifts in K-LL Auger energies and LL ionization potentials. Secondly chemical shifts of K-LL Auger energies of a series of model molecules H₂S, H₂SO₄, H₄SO₂ and H₂SO₂ are correlated with the formal oxidation state of sulphur. This correlation gives a shift of 12 eV in Auger energy per formal charge on sulphur.     

A formal [3 + 3] cycloaddition reaction. Improved reactivity using alpha,beta-unsaturated iminium salts and evidence for reversibility of 6pi-electron electrocyclic ring closure of 1-oxatrienes

A detailed account regarding a formal [3 + 3] cycloaddition method using 4-hydroxy-2-pyrones and 1,3-diketones is described here. This formal cycloaddition reaction or annulation reaction is synthetically useful for constructing 2H-pyranyl heterocycles. The usage of alpha,beta-unsaturated iminium salts is significant in controlling competing reaction pathways to give exclusively 2H-pyrans. Most significantly, experimental evidence is provided to support the mechanism of this reaction that involves a sequential Knoevenagel condensation and a reversible 6pi-electron electrocyclic ring-closure of 1-oxatrienes.