23.7 Alkylation and Acylation Reactions of Amines 1131
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Part I: Carbonyl-Olefin Metathesis of Norbornene
Part I: Carbonyl-Olefin Metathesis of Norbornene Part II: Cyclopropenimine-Catalyzed Asymmetric Michael Reactions Zara Maxine Seibel Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2016 1 © 2016 Zara Maxine Seibel All Rights Reserved 2 ABSTRACT Part I: Carbonyl-Olefin Metathesis of Norbornene Part II: Cyclopropenimine-Catalyzed Asymmetric Michael Reactions Zara Maxine Seibel This thesis details progress towards the development of an organocatalytic carbonyl- olefin metathesis of norbornene. This transformation has not previously been done catalytically and has not been done in practical manner with stepwise or stoichiometric processes. Building on the previous work of the Lambert lab on the metathesis of cyclopropene and an aldehyde using a hydrazine catalyst, this work discusses efforts to expand to the less stained norbornene. Computational and experimental studies on the catalytic cycle are discussed, including detailed experimental work on how various factors affect the difficult cycloreversion step. The second portion of this thesis details the use of chiral cyclopropenimine bases as catalysts for asymmetric Michael reactions. The Lambert lab has previously developed chiral cyclopropenimine bases for glycine imine nucleophiles. The scope of these catalysts was expanded to include glycine imine derivatives in which the nitrogen atom was replaced with a carbon atom, and to include imines derived from other amino acids. i Table of Contents List of Abbreviations…………………………………………………………………………..iv Part I: Carbonyl-Olefin Metathesis…………………………………………………………… 1 Chapter 1 – Metathesis Reactions of Double Bonds………………………………………….. 1 Introduction………………………………………………………………………………. 1 Olefin Metathesis………………………………………………………………………… 2 Wittig Reaction…………………………………………………………………………... 6 Tebbe Olefination………………………………………………………………………... 9 Carbonyl-Olefin Metathesis……………………………………………………………. -
Open PS Thesis - Clara Capparelli
The Pennsylvania State University The Graduate School Department of Material Science and Engineering INFLUENCE OF CARBON SPACERS AND ALKYL PENDANT CHAINS ON THE STABILITY OF QUATERNARY AMMONIUM CATIONS FOR ANION EXCHANGE MEMBRANES A Thesis in Material Science and Engineering by Clara Capparelli 2015 Clara Capparelli Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Science August 2015 The thesis of Clara Capparelli was reviewed and approved* by the following: Michael A. Hickner Associate Professor of Materials Science and Engineering Thesis Advisor James Runt Professor of Polymer Science T.C. Mike Chung Professor of Material Science and Engineering Suzanne Mohney Professor of Material Science and Engineering and Electrical Engineering Chair, Intercollege Graduate Degree Program in Material Science and Engineering *Signatures are on file in the Graduate School iii ABSTRACT Proton and anion exchange membranes are of great importance in the function of fuel cells, one of the most promising technologies for renewable energy conversion. Proton exchange membrane fuel cells (PEMFC) have been studied extensively in the past couple of decades, and there have been tremendous advances in the development of these systems, especially in industries such as automotive and portable power. Anion exchange membranes (AEM) have caught the attention of scientists because they would allow for the development of fuel cells without costly precious metal catalysts, among other advantages. Efforts are being made in developing long-lived and high performance AEMs for fuel cell applications. Primarily, the focus in AEM research has been membrane stability. It has been observed that AEMs are not as stable as the state-of-the-art NAFION® PEM and demonstrations of cell performance beyond 1000 hours is rare. -
Amide Activation: an Emerging Tool for Chemoselective Synthesis
Featuring work from the research group of Professor As featured in: Nuno Maulide, University of Vienna, Vienna, Austria Amide activation: an emerging tool for chemoselective synthesis Let them stand out of the crowd – Amide activation enables the chemoselective modification of a large variety of molecules while leaving many other functional groups untouched, making it attractive for the synthesis of sophisticated targets. This issue features a review on this emerging field and its application in total synthesis. See Nuno Maulide et al., Chem. Soc. Rev., 2018, 47, 7899. rsc.li/chem-soc-rev Registered charity number: 207890 Chem Soc Rev View Article Online REVIEW ARTICLE View Journal | View Issue Amide activation: an emerging tool for chemoselective synthesis Cite this: Chem. Soc. Rev., 2018, 47,7899 Daniel Kaiser, Adriano Bauer, Miran Lemmerer and Nuno Maulide * It is textbook knowledge that carboxamides benefit from increased stabilisation of the electrophilic carbonyl carbon when compared to other carbonyl and carboxyl derivatives. This results in a considerably reduced reactivity towards nucleophiles. Accordingly, a perception has been developed of amides as significantly less useful functional handles than their ester and acid chloride counterparts. Received 27th April 2018 However, a significant body of research on the selective activation of amides to achieve powerful DOI: 10.1039/c8cs00335a transformations under mild conditions has emerged over the past decades. This review article aims at placing electrophilic amide activation in both a historical context and in that of natural product rsc.li/chem-soc-rev synthesis, highlighting the synthetic applications and the potential of this approach. Creative Commons Attribution 3.0 Unported Licence. -
Detection of Phenethylamine, Amphetamine, and Tryptamine Imine By-Products from an Acetone Extraction
Detection of Phenethylamine, Amphetamine, and Tryptamine Imine By-Products from an Acetone Extraction Mary A. Yohannan* and Arthur Berrier U.S. Department of Justice Drug Enforcement Administration Special Testing and Research Laboratory 22624 Dulles Summit Court Dulles, VA 20166 [email: mary.a.yohannan -at- usdoj.gov] ABSTRACT: The formation of imine by-products from phenethylamines, amphetamines, and tryptamines upon an acetone extraction is presented. These imine by-products were characterized using GC/MSD and exhibited preferential cleavage at the α-carbon of the alkyl chain. Further characterization of the imine by-products of phenethylamine and tryptamine was done using IR and NMR. KEYWORDS: phenethylamine, tryptamine, imine, acetone, schiff base, drug chemistry, forensic chemistry In most forensic laboratories, the solvents used to extract at the α-carbon on the alkyl chain. In addition to GC/MS, the drugs are chosen based upon their solubility properties and their imines formed from phenethylamine base and tryptamine base ability to not interact with the drug. In fact, there are very few were characterized by Fourier transform-infrared spectroscopy publications where a solvent used to extract a drug reacts with (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. the drug and forms by-products [1-3]. This laboratory recently discovered that an additional Experimental component was formed when acetone was used to extract a Solvents, Chemicals, and Materials sample containing a known tryptamine. Analysis by gas Acetone was ACS/HPLC grade from Burdick and Jackson chromatography/mass spectroscopy (GC/MS) of the acetone Laboratories (Muskegon, MI). Phenethylamine base and extract yielded an extra peak in the total ion chromatogram that tryptamine base were obtained from Sigma-Aldrich Chemicals was approximately half the abundance of the known tryptamine (Milwaukee, WI). -
6 Synthesis of N-Alkyl Amino Acids Luigi Aurelio and Andrew B
j245 6 Synthesis of N-Alkyl Amino Acids Luigi Aurelio and Andrew B. Hughes 6.1 Introduction Among the numerous reactions of nonribosomal peptide synthesis, N-methylation of amino acids is one of the common motifs. Consequently, the chemical research community interested in peptide synthesis and peptide modification has generated a sizeable body of literature focused on the synthesis of N-methyl amino acids (NMA). That literature is summarized herein. Alkyl groups substituted on to nitrogen larger than methyl are exceedingly rare among natural products. However, medicinal chemistry programs and peptide drug development projects are not limited to N-methylation. While being a much smaller body of research, there is a range of methods for the N-alkylation of amino acids and those reports are also covered in this chapter. The literature on N-alkyl, primarily N-methyl amino acids comes about due to the useful properties that the N-methyl group confers on peptides. N-Methylation increases lipophilicity, which has the effect of increasing solubility in nonaqueous solvents and improving membrane permeability. On balance this makes peptides more bioavailable and makes them better therapeutic candidates. One potential disadvantage is the methyl group removes the possibility of hydro- gen bonding and so binding events may be discouraged. It is notable though that the N-methyl group does not fundamentally alter the identity of the amino acid. Some medicinal chemists have taken advantage of this fact to deliberately discourage binding of certain peptides that can still participate in the general or partial chemistry of a peptide. A series of recent papers relating to Alzheimers disease by Doig et al. -
The Carcinogenicity of the O-Methoxy Derivatives of N-2-Fluorenylacetamide and of Related Compounds in the Rat
[CANCER RESEARCH 28, 234-244, February 1968] The Carcinogenicity of the o-Methoxy Derivatives of N-2-Fluorenylacetamide and of Related Compounds in the Rat H. R. Gutmann, S. B. Galitski, and W. A. Foley Laboratory ]or Cancer Research, Veterans Administration Hospital, and Department o] Biochemistry, University o] Minnesota, Minneapolis, Minnesota 55417 SUMMARY acetamide by the sequential reactions of deacetylation and oxidation. In order to test the idea that the lack of carcinogenicity of the o-amidofluorenols, N- (1-hydroxy-2-fluorenyl) acetamide and INTRODUCTION N-(3-hydroxy-2-fluorenyl)acetamide, is due to the hydrophilic phenolic hydroxyl group, the methylated derivatives, N-(1- Several model studies from this laboratory have shown that methoxy-2-fluorenyl)acetamide and N-(3-methoxy-2-fluorenyl) the o-quinone imines, 2-imino-l,2-fluorenoquinone and 2-imino- acetamide as well as the hydrochlorides of 1-methoxy-2-fluo- 2,3-fluorenoquinone, which are derived from the carcinogen renamine and 3-methoxy-2-fiuorenamine, were prepared, and N-2-fluorenylacetamide by the sequential enzymatic reactions their carcinogenicity was evaluated in the rat. N-(1-Methoxy- of hydroxylation, deacetylation, and oxidation (6, 10, 12, 27, 2-fluorenyl)acetamide and 1-methoxy-2-fluorenamine hydro- 34, 35), form stable adducts with a variety of proteins (17, 18). chloride, when administered orally to male rats for 5 months, However, the relevance of the binding of these o-quinone imines gave a tumor incidence of 27 and 50%, respectively. Approxi- to chemical carcinogenesis has remained obscure largely be- mately one-half of the lesions produced by either com- cause the o-amidofluorenols, 1-OH-AAF 2 and 3-OH-AAF pound were adenocarcinomas of the small intestine. -
Subject Index
455 Subject Index Aminohydroxylation, 364 a-Aminoketone, 281 4-Aminophenol, 18 A Aminothiophene, 158 Abnormal Claisen rearrangement, 1 a-Aminothiophenols, 184 Acrolein, 378 Ammonium ylide, 383 2-(Acylamino)-toluenes, 245 Angeli-Rimini hydroxamic acid Acylation, 100, 145, 200 synthesis, 9 Acyl azides, 98 ~-Anomer, 225 Acylium ion, 145, 149, 175, 177 Anomeric center, 211 a-Acyloxycarboxamides, 298 Anomeric effect, 135 a-Acyloxyketones, 17 ANRORC mechanism, 10 a-Acyloxythioethers, 327 Anthracenes, 51 Acyl transfer, 17, 42, 228, 298, 305, Anti-Markovnikov addition, 219 327,345 Amdt-Eistert homologation, 11 AIBN, 22, 23, 415 Aryl-acetylene, 66 Alder ene reaction, 2 Arylation, 253 Alder's endo rule, Ill 0-Aryliminoethers, 67 Aldol condensation, 3, 14, 26, 34, 2-Arylindoles, 38 69, 130, 147, 172, 305, Aryl migration, 31 340,396,412 Autoxidation, 69, 115, 118 Aldosylamine, 8 Auwers reaction, 13 Alkyl migration, 16, 132, 315, 443 Axial, 347 Alkylation, 144, 145 Azalactone, I 00 N-Aikylation, 162 Azides, 125, 330 Alkylidene carbene, 151 Azirine, 6, 7, 281 Allan-Robinson reaction, 4, 228 Azulene, 310 Allene, 119 1t-Allyl complex, 414 B Allylation, 213, 414 Baeyer-Drewson Allylstannane, 213 indigo synthesis, 14 Allylsilanes, 349 Baeyer-Villiger oxidation, 16, 53 Alper carbonylation, 6 Baker-Venkataraman Alpine-borane®, 262 rearrangement, 17 Aluminum phenolate, 149 Balz-Schiemann reaction, 354 Amadori rearrangement, 8 Bamberger rearrangement, 18 Amide acetal, 74 Bamford-Stevens reaction, 19 Amides, 28, 67,276,339, 356 Bargellini reaction, 20 Amidine, -
Solvating Alkylamine Hofmann Elimination in Zeolites Through Cooperative Adsorption Han Chen† and Omar A
Solvating Alkylamine Hofmann Elimination in Zeolites Through Cooperative Adsorption Han Chen† and Omar A. Abdelrahman †,‡* † Department of Chemical Engineering, University of Massachusetts Amherst, 686 N. Pleasant Street, Amherst, MA 01003, USA ‡ Catalysis Center for Energy Innovation, University of Delaware, 150 Academy Street, Newark, DE 19716, USA *Corresponding Author: [email protected] Abstract. A kinetic investigation of the vapor phase Hofmann elimination of tert-butylamine over H- ZSM-5 reveals a carbocation mediated E1-like mechanism, where isobutene and ammonia are exclusively produced over Brønsted acid sites. Hofmann elimination kinetics are found to be insensitive to Al content or siting, varying only with alkylamine carbocation stability (rtertiary > rsecondary > rprimary). Under conditions of complete tert-butylamine surface coverage, experimentally measurable apparent kinetics are directly equivalent to the intrinsic kinetics of the rate determining unimolecular surface elimination. The direct measurement of elementary step kinetics served as a water-free reactive probe, providing a direct measurement of the impact of water on solid Brønsted acid catalyzed chemistries at a microscopic level. Over a range of temperatures (453‒513 K) and tert-butylamine partial pressures (6.8×10-2‒6.8 kPa), water reversibly inhibits the rate of Hofmann elimination. Despite expected changes in aluminosilicate hydrophobicity, the water-induced inhibition is found to be insensitive to Al content, demonstrated to be due to one water molecule per Brønsted acid site. Regardless of the significant reduction in the rate of Hofmann elimination, kinetic interrogations and operando spectroscopic measurements reveal that the coverage of TBA adsorbed on H-ZSM-5 is unaltered in the presence of water. -
Synthesis and Characterization of Novel Imine-Linked Covalent Organic Frameworks
Synthesis and Characterization of Novel Imine-Linked Covalent Organic Frameworks THESIS Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University By Toni Beirl Graduate Program in Chemistry The Ohio State University 2015 Master's Examination Master's Examination Committee: Professor Psaras McGrier, Advisor Professor Jovica D. Badjic Copyrighted by Toni M.Beirl 2015 Abstract Covalent organic frameworks (COFs) are a class of porous crystalline materials composed of light elements (such as H, B, C, N, and O) that are linked by covalent bonds. The modular nature of COFs permits the integration of various π-conjugated molecular building blocks into highly ordered polymeric structures with low densities and high thermal stabilities making them suitable for applications related to energy storage and conversion, catalysis, and gas storage. Since a majority of the early examples of COFs contained boroxine or boronate esters linkages, many of these materials were often susceptible to hydrolysis when exposed to aqueous conditions resulting in decomposition of the framework. The recent discovery of imine-linked COFs has sparked the creation of COFs with superior chemical stability on account of an intramolecular hydrogen bond between the hydroxyl and imine functional groups, which enhances their stability in aqueous and acidic environments. Utilizing this feature, this thesis examines the synthesis and gas adsorption properties of novel imine-linked COFs that contain 1,3,5-tris(styryl)benzene and 1,3,5– tris(arylethynyl)benzene π-conjugated units. By creating analogs which were fluorescent in both solution and solid-state, studies were conducted to determine their ability to serve as chemical sensors for explosives. -
Organic Seminar Abstracts
L I B RA R.Y OF THE UN IVE.R.SITY Of ILLI NOIS 547 l£6s \ 954/55 PV Return this book on or before the Latest Date stamped below. University of Illinois Library Llf.1—H41 Digitized by the Internet Archive in 2012 with funding from University of Illinois Urbana-Champaign http://archive.org/details/organicsemi195455univ \7^ — SEMINAR TOPICS CHEMISTRY 435 I Semester 1954-55 The Quinolizinium Ion and Some of its Derivatives Harvey M. Loux, September 24 1 The Stereochemistry of Atropine and Cocaine Ho E . Knipmeyer, September 24 4 Recent Developments in the Chemistry of Cinnoline Derivatives Roger H. Kottke , October 1 8 Interpretation of Electrophiiic Aromatic Substitution and Solvolysis of Allylic and Benzhydryl Chlorides in Terms of Hyperconjugation Robert D. Stolow, October 1 11 The Decahydronaphtholic Acids and Their Relationship to the Decalols and the Decalylamines Robert J. Harder, October 8 14 Bis-Cyclopentadienyl Metal Compounds Edwin L. DeYoung, October 8 17 Ion-Pairs as Intermediates in Solvolysis Reactions Arthur H. Goldkamp, October 15 21 Synthesis of Morphine Mohan D. Nair, October 15 24 Structural and Geometrical Isomerism in the Oxidation of Azo Compounds D. F. Morrow, October 22 27 Stereochemical Aspects of Thermochromism John W. Johnson, Jr., October 22 30 A New Method for the Preparation of Olefins --The Pyrolysis of Sulfites F. M. Scheidt, October 29 33 Recent Studies of Macrocyclic Ring Systems: Cyclophanes Fred P. Hauck, Jr., October 29 36 Mechanism of the Para-Claisen Rearrangement Hugh H . Gibbs , November 5 40 A Proposed Mechanism for Basic c is -Dehydrohalogenat ion Robert M. -
A General N-Alkylation Platform Via Copper Metallaphotoredox and Silyl Radical Activation of Alkyl Halides
ll Article A general N-alkylation platform via copper metallaphotoredox and silyl radical activation of alkyl halides Nathan W. Dow, Albert Cabre´, David W.C. MacMillan [email protected] Highlights General, room temperature N- alkylation via copper metallaphotoredox catalysis Broad reactivity across diverse alkyl bromides, N-heterocycles, and pharmaceuticals Convenient approach to N- cyclopropylation using easily handled bromocyclopropane Readily extended to functionalization of unactivated secondary alkyl chlorides Traditional substitution reactions between nitrogen nucleophiles and alkyl halides feature well-established, substrate-dependent limitations and competing reaction pathways under thermally induced conditions. Herein, we report that a metallaphotoredox approach, utilizing a halogen abstraction-radical capture (HARC) mechanism, provides a valuable alternative to conventional N-alkylation. This visible-light-induced, copper-catalyzed protocol is successful for coupling >10 classes of N-nucleophiles with diverse primary, secondary, or tertiary alkyl bromides. Moreover, this open-shell platform alleviates outstanding N-alkylation challenges regarding regioselectivity, direct cyclopropylation, and secondary alkyl chloride functionalization. Dow et al., Chem 7,1–16 July 8, 2021 ª 2021 Elsevier Inc. https://doi.org/10.1016/j.chempr.2021.05.005 Please cite this article in press as: Dow et al., A general N-alkylation platform via copper metallaphotoredox and silyl radical activation of alkyl halides, Chem (2021), https://doi.org/10.1016/j.chempr.2021.05.005 -
Elimination Reactions Are Described
Introduction In this module, different types of elimination reactions are described. From a practical standpoint, elimination reactions widely used for the generation of double and triple bonds in compounds from a saturated precursor molecule. The presence of a good leaving group is a prerequisite in most elimination reactions. Traditional classification of elimination reactions, in terms of the molecularity of the reaction is employed. How the changes in the nature of the substrate as well as reaction conditions affect the mechanism of elimination are subsequently discussed. The stereochemical requirements for elimination in a given substrate and its consequence in the product stereochemistry is emphasized. ELIMINATION REACTIONS Objective and Outline beta-eliminations E1, E2 and E1cB mechanisms Stereochemical considerations of these reactions Examples of E1, E2 and E1cB reactions Alpha eliminations and generation of carbene I. Basics Elimination reactions involve the loss of fragments or groups from a molecule to generate multiple bonds. A generalized equation is shown below for 1,2-elimination wherein the X and Y from two adjacent carbon atoms are removed, elimination C C C C -XY X Y Three major types of elimination reactions are: α-elimination: two atoms or groups are removed from the same atom. It is also known as 1,1-elimination. H R R C X C + HX R Both H and X are removed from carbon atom here R Carbene β-elimination: loss of atoms or groups on adjacent atoms. It is also H H known as 1,2- elimination. R C C R R HC CH R X H γ-elimination: loss of atoms or groups from the 1st and 3rd positions as shown below.