Lecture 13 Electrophilic Aromatic Substitution I 5.1 Principles
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A Facile Procedure for the Generation of Dichlorocarbene from the Reaction of Carbon Tetrachloride and Magnesium Using Ultrasonic Irradiation
Molecules 2003, 8, 608-613 molecules ISSN 1420-3049 http://www.mdpi.org A Facile Procedure for the Generation of Dichlorocarbene from the Reaction of Carbon Tetrachloride and Magnesium using Ultrasonic Irradiation Haixia Lin *, Mingfa Yang, Peigang Huang and Weiguo Cao Department of Chemistry, Shanghai University, Shanghai, 200436, P.R. China *Author to whom correspondence should be addressed: e-mail [email protected] Received: 7 April 2003; in revised form: 7 July 2003 / Accepted: 20 July 2003 / Published: 31 July 2003 Abstract: An improved method for the generation of dichlorocarbene was developed that utilizes ultrasound in the reaction of carbon tetrachloride with magnesium. High yields of gem-dichlorocyclopropane derivatives can be obtained in the presence of olefins by this method. Keywords: Dichlorocarbene; gem-dichlorocyclopropanes; ultrasonic irradiation; olefin addition; magnesium Introduction Gem-dichlorocyclopropanes are valuable intermediates in organic synthesis [1,2]. They are typically prepared by the addition of dichlorocarbene to olefins under phase-transfer catalysis conditions [3-5]. Sonochemical generation of dichlorocarbene has also been reported [6-8]. The reactions of dichlorocarbene with olefins in solid-liquid two-phase systems using ultrasonication usually afford high yields of double-bond addition products. In addition, excellent yields of diadducts have been obtained from dienes and dichlorocarbene under ultrasonication and phase-transfer catalyst [9]. Molecules 2003, 8 609 Previously, we reported a novel route for the generation of dichlorocarbene by the reaction of carbon tetrachloride with magnesium in a neutral medium and hypothesized that the mechanism of these reactions might involve a single electron transfer [10]. However, these reactions suffered from several experimental drawbacks: some of the major ones being the sudden exotherm that occurs after an unpredictable induction period, foaming, and in some cases, the use of iodine as the activating agent. -
Recent Advances in Titanium Radical Redox Catalysis
JOCSynopsis Cite This: J. Org. Chem. 2019, 84, 14369−14380 pubs.acs.org/joc Recent Advances in Titanium Radical Redox Catalysis Terry McCallum, Xiangyu Wu, and Song Lin* Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States ABSTRACT: New catalytic strategies that leverage single-electron redox events have provided chemists with useful tools for solving synthetic problems. In this context, Ti offers opportunities that are complementary to late transition metals for reaction discovery. Following foundational work on epoxide reductive functionalization, recent methodological advances have significantly expanded the repertoire of Ti radical chemistry. This Synopsis summarizes recent developments in the burgeoning area of Ti radical catalysis with a focus on innovative catalytic strategies such as radical redox-relay and dual catalysis. 1. INTRODUCTION a green chemistry perspective, the abundance and low toxicity of Ti make its complexes highly attractive as reagents and Radical-based chemistry has long been a cornerstone of 5 1 catalysts in organic synthesis. synthetic organic chemistry. The high reactivity of organic IV/III radicals has made possible myriad new reactions that cannot be A classic example of Ti -mediated reactivity is the reductive ring opening of epoxides. This process preferentially readily achieved using two-electron chemistry. However, the − high reactivity of organic radicals is a double-edged sword, as cleaves and functionalizes the more substituted C O bond, the selectivity of these fleeting intermediates can be difficult to providing complementary regioselectivity to Lewis acid control in the presence of multiple chemotypes. In addition, promoted epoxide reactions. The synthetic value of Ti redox catalysis has been highlighted by their many uses in total catalyst-controlled regio- and stereoselective reactions involv- 6−10 ing free-radical intermediates remain limited,2 and the synthesis (Scheme 1). -
Chloroform 18.08.2020.Pdf
Chloroform Chloroform, or trichloromethane, is an organic compound with formula CHCl3. It is a colorless, sweet-smelling, dense liquid that is produced on a large scale as a precursor to PTFE. It is also a precursor to various refrigerants. It is one of the four chloromethanes and a trihalomethane. It is a powerful anesthetic, euphoriant, anxiolytic and sedative when inhaled or ingested. Formula: CHCl₃ IUPAC ID: Trichloromethane Molar mass: 119.38 g/mol Boiling point: 61.2 °C Density: 1.49 g/cm³ Melting point: -63.5 °C The molecule adopts a tetrahedral molecular geometry with C3v symmetry. Chloroform volatilizes readily from soil and surface water and undergoes degradation in air to produce phosgene, dichloromethane, formyl chloride, carbon monoxide, carbon dioxide, and hydrogen chloride. Its half-life in air ranges from 55 to 620 days. Biodegradation in water and soil is slow. Chloroform does not significantly bioaccumulate in aquatic organisms. Production:- In industry production, chloroform is produced by heating a mixture of chlorine and either chloromethane (CH3Cl) or methane (CH4). At 400–500 °C, a free radical halogenation occurs, converting these precursors to progressively more chlorinated compounds: CH4 + Cl2 → CH3Cl + HCl CH3Cl + Cl2 → CH2Cl2 + HCl CH2Cl2 + Cl2 → CHCl3 + HCl Chloroform undergoes further chlorination to yield carbon tetrachloride (CCl4): CHCl3 + Cl2 → CCl4 + HCl The output of this process is a mixture of the four chloromethanes (chloromethane, dichloromethane, chloroform, and carbon tetrachloride), which can then be separated by distillation. Chloroform may also be produced on a small scale via the haloform reaction between acetone and sodium hypochlorite: 3 NaClO + (CH3)2CO → CHCl3 + 2 NaOH + CH3COONa Deuterochloroform[ Deuterated chloroform is an isotopologue of chloroform with a single deuterium atom. -
Asymmetric Lewis Acid Catalysis Directed by Octahedral Rhodium Centrochirality† Cite This: Chem
Chemical Science View Article Online EDGE ARTICLE View Journal | View Issue Asymmetric Lewis acid catalysis directed by octahedral rhodium centrochirality† Cite this: Chem. Sci.,2015,6,1094 Chuanyong Wang,‡a Liang-An Chen,‡b Haohua Huo,a Xiaodong Shen,a Klaus Harms,a Lei Gongb and Eric Meggers*ab A rhodium-based asymmetric catalyst is introduced which derives its optical activity from octahedral centrochirality. Besides providing the exclusive source of chirality, the rhodium center serves as a Lewis acid by activating 2-acyl imidazoles through two point binding and enabling a very effective asymmetric induction mediated by the propeller-like C2-symmetrical ligand sphere. Applications to asymmetric Michael additions (electrophile activation) as well as asymmetric a-aminations (nucleophile activation) Received 9th October 2014 are disclosed, for which the rhodium catalyst is found to be overall superior to its iridium congener. Due Accepted 7th November 2014 to its straightforward proline-mediated synthesis, high catalytic activity (catalyst loadings down to 0.1 DOI: 10.1039/c4sc03101f mol%), and tolerance towards moisture and air, this novel class of chiral-at-rhodium catalysts will likely www.rsc.org/chemicalscience to become of widespread use as chiral Lewis acid catalysts for a large variety of asymmetric transformations. Creative Commons Attribution 3.0 Unported Licence. Lewis acids are capable of activating a large variety of carbon- now wish to report for the rst time that rhodium can also serve heteroatom and carbon–carbon bond forming reactions and as the combined source of centrochirality and Lewis acidity in chiral Lewis acids have therefore become indispensable tools substitutionally labile octahedral metal complexes. -
Methionine Aminopeptidase Emerging Role in Angiogenesis
Chapter 2 Methionine Aminopeptidase Emerging role in angiogenesis Joseph A. Vetro1, Benjamin Dummitt2, and Yie-Hwa Chang2 1Department of Pharmaceutical Chemistry, University of Kansas, 2095 Constant Ave., Lawrence, KS 66047, USA. 2Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University Health Sciences Center, 1402 S. Grand Blvd., St. Louis, MO 63104, USA. Abstract: Angiogenesis, the formation of new blood vessels from existing vasculature, is a key factor in a number of vascular-related pathologies such as the metastasis and growth of solid tumors. Thus, the inhibition of angiogenesis has great potential as a therapeutic modality in the treatment of cancer and other vascular-related diseases. Recent evidence suggests that the inhibition of mammalian methionine aminopeptidase type 2 (MetAP2) catalytic activity in vascular endothelial cells plays an essential role in the pharmacological activity of the most potent small molecule angiogenesis inhibitors discovered to date, the fumagillin class. Methionine aminopeptidase (MetAP, EC 3.4.11.18) catalyzes the non-processive, co-translational hydrolysis of initiator N-terminal methionine when the second residue of the nascent polypeptide is small and uncharged. Initiator Met removal is a ubiquitous and essential modification. Indirect evidence suggests that removal of initiator Met by MetAP is important for the normal function of many proteins involved in DNA repair, signal transduction, cell transformation, secretory vesicle trafficking, and viral capsid assembly and infection. Currently, much effort is focused on understanding the essential nature of methionine aminopeptidase activity and elucidating the role of methionine aminopeptidase type 2 catalytic activity in angiogenesis. In this chapter, we give an overview of the MetAP proteins, outline the importance of initiator Met hydrolysis, and discuss the possible mechanism(s) through which MetAP2 inhibition by the fumagillin class of angiogenesis inhibitors leads to cytostatic growth arrest in vascular endothelial cells. -
Research in the Department of Homogeneous Catalysis
Homogeneous Catalysis – Overview Research in the Department of Homogeneous Catalysis Researchers in our department continue focusing on the development of new catalysis concepts within the areas of organocatalysis and transition metal catalysis. We explore new catalysts, expand the substrate scope of certain catalytic reactions, apply asymmetric catalysis in natural product and pharmaceutical synthesis, and study mechanisms of homogenous catalytic reactions (B. List, K.-R. Pörschke, M. Klußmann, N. Maulide). Since leadership of the department of homogenous catalysis was taken over by Professor Benjamin List in 2005, it has grown significantly from ca. 15 members to currently > 50 members, including the groups of Professor K.-R. Pörschke, who has been a group leader at the institute since two decades now, Dr. M. Klußmann (group leader since 2007), and now also of Dr. N. Maulide, who has joined the department in 2009. The group of Professor List primarily advances enantioselective organocatalysis as a fundamental approach complementing the already more advanced fields of biocatalysis and transition metal catalysis. The List group has a profound interest in developing “new reactions”, designs and identifies new principles for the development of organocatalysts, expands the scope of already developed catalysts such as proline, uses organocatalysis in the synthesis of natural products and pharmaceuticals, and also investigates the mechanism by which organocatalysts activate their substrates. Furthermore, in 2005 the group has first conceptualized and then significantly advanced another approach to asymmetric catalysis, asymmetric counteranion directed catalysis (ACDC). Initially, merely an idea, this approach has progressed within the department but now also at other institutions around the globe, into a truly general strategy for asymmetric synthesis and has found utility in organocatalysis but also in transition metal catalysis and Lewis acid catalysis. -
Gas-Solid Alkali Destruction of Volatile Chlorocarbons
LA-13042-MS Gas-Solid Alkali Destruction of Volatile Chlorocarbons c£lVi •% to BO Los Alamos NATIONAL LABORATORY Los Alamos National Laboratory is operated by the University of California for the United States Department of Energy under contract W-7405-ENG-36- An Affirmative Action/Equal Opportunity Employer This report was prepared as an account of work sponsored by an agency of the United States Government. Neither The Regents of the University of California, the United States Government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise, does not necessarily constitute or imply its endorsement, recommendation, or favoring by The Regents of the University of California, the United States Government, or any agency thereof. The views and opinions of authors expressed herein do not necessarily state or reflect those of The Regents of the University of California, the United States Government, or any agency thereof. The Los Alamos National Laboratory strongly supports academic freedom and a researcher's right to publish; therefore, the Laboratory as an institution does not endorse the viewpoint of a publication or guarantee its technical correctness. DISCLAIMER Portions of this document may be illegible in electronic image products. Images are produced from the best aTaiiable original document. LA-13042-MS UC-901 Issued: December 1995 Gas-Solid Alkali Destruction of Volatile Chlorocarbons Jerry Foropoulos, Jr. -
Reactions of Aromatic Compounds Just Like an Alkene, Benzene Has Clouds of Electrons Above and Below Its Sigma Bond Framework
Reactions of Aromatic Compounds Just like an alkene, benzene has clouds of electrons above and below its sigma bond framework. Although the electrons are in a stable aromatic system, they are still available for reaction with strong electrophiles. This generates a carbocation which is resonance stabilized (but not aromatic). This cation is called a sigma complex because the electrophile is joined to the benzene ring through a new sigma bond. The sigma complex (also called an arenium ion) is not aromatic since it contains an sp3 carbon (which disrupts the required loop of p orbitals). Ch17 Reactions of Aromatic Compounds (landscape).docx Page1 The loss of aromaticity required to form the sigma complex explains the highly endothermic nature of the first step. (That is why we require strong electrophiles for reaction). The sigma complex wishes to regain its aromaticity, and it may do so by either a reversal of the first step (i.e. regenerate the starting material) or by loss of the proton on the sp3 carbon (leading to a substitution product). When a reaction proceeds this way, it is electrophilic aromatic substitution. There are a wide variety of electrophiles that can be introduced into a benzene ring in this way, and so electrophilic aromatic substitution is a very important method for the synthesis of substituted aromatic compounds. Ch17 Reactions of Aromatic Compounds (landscape).docx Page2 Bromination of Benzene Bromination follows the same general mechanism for the electrophilic aromatic substitution (EAS). Bromine itself is not electrophilic enough to react with benzene. But the addition of a strong Lewis acid (electron pair acceptor), such as FeBr3, catalyses the reaction, and leads to the substitution product. -
L. Lewis Acid Catalysis
L. LEWIS ACID CATALYSIS Background Twenty amino acids is not enough. The breadth of chemistry handled by enzymes requires that additional chemical species be employed in catalysis. So-called cofactors are non-amino acid components of enzymes that may be either associated or bonded to proteins and contribute to rate acceleration. Roughly one-third of all enzymes studied to date employ metal ion cofactors. Metal cations can play one of two roles; they may act as Lewis acids or as redox reagents. As Lewis acids, they function in a role similar to general acids, stabilizing negative charge in the enzyme active site. This chapter will focus on Lewis acid catalysis in reactions that employ water as a nucleophile. Lewis acid catalysis can be observed to play a role in either (a) activating water as a nucleophile or (b) activating the electrophile for nucleophilic attack. Activation of Water as a Nucleophile As noted earlier, water is a poor nucleophile due to the build up of positive charge on the oxygen that accompanies attack upon an electrophile. General base catalysis overcomes that issue by promoting deprotonation of the water molecule as it attacks. Another approach is to stabilize the hydroxide ion within the enzyme active site. While the metal ion itself is a Lewis acid (electron pair acceptor), the hydrated metal ion is a Bronsted acid (a proton donor) according to Equation L.1. n+ (n-1)+ + M(H2O)6 ⇔ M(H2O)5(OH) + H Eq L.1 In this instance Lewis acidity and Bronsted acidity are linked. The capacity of the metal cation to stabilize negative charge from a hydroxide (hydroxo in inorganic-speak) ligand is a reflection of the Lewis acidity of the cation. -
Bulky Aluminum Lewis Acids As Novel Efficient and Chemoselective
Erschienen in: Synlett ; 1999 (1999), 5. - S. 584-586 https://dx.doi.org/10.1055/s-1999-2667 584 Bulky Aluminum Lewis Acids as Novel Efficient and Chemoselective Catalysts for the Allylation of Aldehydes Andreas Marx, Hisashi Yamamoto* Graduate School of Engineering, Nagoya University, CREST, Chikusa, Nagoya 464-8603, Japan Fax +81(52)789-3222; E-mail: [email protected] position of the bulky phenol ligands resulted in further ac- Abstract: Bulky aluminum Lewis acids such as MAD and MABR celeration of the rate. Thus, methylaluminum bis(4-bro- are introduced as new efficient catalysts in substoichiometric 8,9 amounts for the allylation of aldehydes with allyltributylstannane. mo-2,6-di-tert-butyl-phenoxide) (MABR) performed In addition, chemoselective allylation of a less hindered or aromatic the reaction between 1 and 2 to yield the desired product aldehyde was achieved with catalytic amounts of the carbonyl re- 3 in excellent yield (93%) within 1 h at -20 °C (Table 1, ceptor aluminum tris(2,6-diphenyl-phenoxide) (ATPH). Entry 5). It turned out that MABR is the reagent of choice Keywords: allylation, allyltributylstannane, Lewis acid catalysis, for the catalytic allylation of aldehydes with allyltributyl- MABR, ATPH stannane. It is noteworthy that aluminum tris(2,6-diphe- nylphenoxide) (ATPH)8,9 which is known to complex carbonyl functionalities very tightly due to its bowl-like The Lewis acid promoted allylation of aldehydes using shape11 is capable of promoting catalytic allylation of ben- allystannanes or their less reactive counterparts allylsi- zaldehyde as well (Table 1, Entry 6). Bulkiness of the phe- lanes is a versatile synthetic tool.1 Numerous Lewis acids noxide ligands in the organoaluminum Lewis acids seems ◊ to be a prerequisite for catalytic activity and efficiency. -
Post Translational Modification Significance
Post Translational Modification Significance numismatically.Depositional Rustie Vaughan never theologizes desulphurating tarnal. so denominationally or cross-index any whaups dumpishly. Brandon spiralling Senescence is related to the widespread purge of SUMO protein. The conjoint triad feature is sequence information for proteins. Although here we used sublethal antibiotics to isolate these phenotypic variants, colony size variation has been observed in mycobacteria in a variety of conditions. Moreover, three other modifications have been demonstrated to be required after fusion for modulation of RT activity. Ann Acad Med Singapore. Eukaryotic nuclei has no longer residency time points out the building allosteric effectors to toxic can occur on prevention and control by comparing prepubertal to cell motility. Epigenetic Determinants of Cancer. Protein modifications in parallel workstations and significant roles of significance of the scope of silos used for the polypeptide chain decides about posttranslational modifications mediate signaling? Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow. Reversible PTMs are particularly relevant signaling events because to offer the thrill the possibility to dynamically modulate protein activity in text response to environmental cues or internal stimuli. To borrow significant progress has been death in identifying PTMs on cardiac. The Garcia Lab has developed arguably the best precision mass spectrometry based platform for detecting and quantifying the combinatorial histone PTM code. Several PTMs, most noticeably phosphorylation, are known to directly affect metabolic enzyme activity and this aspect will be the main focus of this review. These software programs facilitate peak detection and matching, data alignment, normalization and statistical analysis. Drugs targeting an being of RNA biology we recruit to as fair-transcriptional control. -
Formaldehyde Treatment of Proteins Enhances Proteolytic Degradation by the Endo-Lysosomal Protease Cathepsin S
www.nature.com/scientificreports OPEN Formaldehyde treatment of proteins enhances proteolytic degradation by the endo‑lysosomal protease cathepsin S Thomas J. M. Michiels1,2, Hugo D. Meiring2, Wim Jiskoot1, Gideon F. A. Kersten1,2 & Bernard Metz2* Enzymatic degradation of protein antigens by endo‑lysosomal proteases in antigen‑presenting cells is crucial for achieving cellular immunity. Structural changes caused by vaccine production process steps, such as formaldehyde inactivation, could afect the sensitivity of the antigen to lysosomal proteases. The aim of this study was to assess the efect of the formaldehyde detoxifcation process on the enzymatic proteolysis of antigens by studying model proteins. Bovine serum albumin, β-lactoglobulin A and cytochrome c were treated with various concentrations of isotopically labelled formaldehyde and glycine, and subjected to proteolytic digestion by cathepsin S, an important endo-lysosomal endoprotease. Degradation products were analysed by mass spectrometry and size exclusion chromatography. The most abundant modifcation sites were identifed by their characteristic MS doublets. Unexpectedly, all studied proteins showed faster proteolytic degradation upon treatment with higher formaldehyde concentrations. This efect was observed both in the absence and presence of glycine, an often-used excipient during inactivation to prevent intermolecular crosslinking. Overall, subjecting proteins to formaldehyde or formaldehyde/glycine treatment results in changes in proteolysis rates, leading to an enhanced degradation speed. This accelerated degradation could have consequences for the immunogenicity and the efcacy of vaccine products containing formaldehyde- inactivated antigens. Enzymatic degradation of antigens is a crucial step in the process of acquiring cellular immunity, e.g., through the induction of antigen specifc T-helper cells or cytotoxic T-cells.