DOCSLIB.ORG

20. Phosphorus Chemistry

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
20. Phosphorus Chemistry Professor David L. Van Vranken Chemistry 201: Organic Reaction Mechanisms I Topic 20: Phosphorus Chemistry References: Literature cited Phosphorus Functional Groups ■ Here’s how to name phosphorus functional groups: R R R OR R OR O O R P P P R P P(III) R R OR O R phosphine phosphinite phosphonite phosphite (ester) O O O O R R R OR R OR O O P P P R P R P(V) R R OR O R phosphine oxide phosphinate phosphonate phosphate (ester) ■ Few of these functional groups are common. O O O H P N P HO OH O CH HO F 3 glyphosate sarin Phosphorus Functional Groups ■ pKas reveal the difference in basicity between trialkylphosphines and triarylphosphines Et Ph .. + + N N Ph2N Et Et Ph Ph resonance H H reduces l.p. basicity pKa 11 ~ -5 .. Bu Ph Ph P + + 2 P P not so much Bu Bu Ph Ph H H resonance pKa 9 3 ■ Trialkylphosphines are way more nucleophilic than triarylphosphines Bu Ph Bu P: Ph P: Bu Ph way more nucleophilic Howard ST, et al. Can. J. Chem. 1997, 75, 60. Allman, T.; Goel, R. G. Can. J. Chem. 1982, 60, 716.. POCl3 is a Very Reactive Electrophile ■ Old conditions for elimination of OH groups. Contrast the outcomes. SOCl Cl 2 pyridine OH POCl3 pyridine (solvent) ■ Phosphates don’t substitute very quickly, but Cl3P=O is special ■ Vilsmeier-Haack Reaction - amides attack Cl3P=O + NMe O Cl NMe 2 2 E.A.S. MeO + MeO H2O MeO H OMe OMe workup OMe POCl3 + DMF Mechanism for formation of the Vilsmeier reagent: : .. + + O O -O O NMe O NMe O O - + 2 O 2 P NMe P .. P P Cl 2 Cl Cl N Cl Cl Cl Cl Cl Cl Cl Cl :Cl- Phosphates as Leaving Groups and/or Electrophiles ■ Phosphates are good leaving groups. In biology magnesium-diphosphophate is the most common leaving group leaving group leaving group .. - O O O OR O O P P P nucleoside P P -O O O O -O O O R O O O O O Mg Mg ■ In acid-hydrolysis of trimethyl phosphate, C-O bond cleavage competes with P-O bond cleavage because phosphates are good leaving groups and it is difficult to attack a phosphate. O HCl O P HOCH H3CO OCH P 3 3 H3CO OH H3CO H2O H3CO - H + H + .. O O .. - HO OH P P CH3 H3CO OCH3 H3CO O H3CO H3CO Hydrolysis of Phosphites and Phosphates ■ Phosphites hydrolyze much faster than phosphates. phosphate phosphite O .. P P F. Westheimer RO OR RO OR RO RO JACS 1988, 181 Chem. Ber. 1960, 1220 HO- 1 1,000 H3O+ 1 1,000,000,000,000 ■ If you want to synthesize P-O bonds use phosphites, n ot phosphates because you can always oxidize a phosphite up to a phosphate later. Modern DNA synthesis is based on the chemistry of phosphites + acid. acid DMTO N DMTO N O NHBz N O NHBz N HN N N N N N N N O pKa 4.9 O NC P NC P O .. N + O .. O + OH 1 minute HN DNA DNA Letsinger, R. L. JACS 1976, 98, 3655. Caruthers,M. H. TL 1983, 24, 245. Mechanism: Fast Acid-Catalyzed Exchange at Phosphites ■ Recall dehydrobromination from sophomore organic chemistry. (cat HA) Br OH 3 OH 3 Br P P Br Br HO OH phosphorane tetrahedral intermediate intermediate don't draw one-step SN2 Nu O - H O: .. P C L.G. R P Br Br L.G. Nu Br ■ The mechanism involves protonation of the phosphite -A: H .. H A Br .. P P P + EtOH Br Br HO Br HO Br Br Br Br H -Br A .. H H O.. H EtO H H Et + + - + P P P : P Br Br Br O Br O Br Br Br Br Br Br P=O Bond Formation Drives Many Reactions ■ Mechanism for oxidation by I2 /H2O in DNA synthesis H B: H H2O: O O O R R B: R R R R P R P R P R P R P R .. + R + R R R I I I I ■ Phosphines oxidize easily .. O O - C O 89 kcal/mol O–O Clayden, et al. R P Ph3P=O 137 kcal/mol R P P + JCS 1960, 3284 R R R R R Bu3P=O 128 kcal/mol R R Bu3P fast, very air sensitive Ph3P slower ■ Convention: Draw P=O, but all the reactivity is best explained by +P—O– D. G. Gilheany “Structure and bonding in tertiary phosphine chalcogenides” Chemistry of Organophosphorus Compounds p. 1-52 Nucleophilicity of Phosphorus ■ Phosphites act as nucleophiles in the Michaelis-Arbuzov reaction; a phosphate acts as a leaving group. OEt O O O . ∆ P . P EtO OEt OEt EtO OEt EtO Br -Br: O O P EtO + OEt EtO Kosolapoff, G. M. Org. React. 1951, 6, 276. Michaelis, A.; Kaehne, R. Ber. 1898, 31, 1048. Arbuzov, A.E. J. Russ. Phys. Chem. Soc. 1906, 38, 687; Chem. Zentr. 1906, II, 1639. Ph3P=O as a Leaving Group ■ Appel reaction. Note attack at halogen in a Br-C bond and the ability of haloform anions to act as leaving groups. Br C—Br :PPh Br 3 3 Ph3P=O + Br3C—H O bromoform H - + : Br3C Br PPh3 -Br : Br Ph Ph PPh Ph O O - O: 3 P Ph P + Br + Ph Ph ■ Note the stability of haloform estimated anions and the ability to act as a cpd pKa (MeOH) leaving group. F3C-H 30.5 Cl3C-H 24.4 Br3C-H 22.7 Streitweiser, A.; et al. I3C-H 22.5 JACS1976, 5229 Ph3P=O as a Leaving Group ■ The Mitsunobu reaction for ”inversion" of alcohols N CO2Et EtO2C N Ar OH + Ph P: PPh 3 3 S 2 O N O O Ph3P=O + HO O .. H O O - N CO2Et Ar EtO2C N Ar H O. Mitsunobu Synthesis 1980, 1 D. L. Hughes Org. React. 1983, 29, 1. Mechanism depends on order of addition Varasi, M.; Walker, K. A. M.; Maddox, M. L. JOC 1987, 52, 4235. The Staudinger Reaction of Azides ■ Recall the stereoelectronics for anti addition to π*. .. antiperiplanar .. X -X ■ The Staudinger mechanism is easily understood if you draw the right resonance structure for N3. easily hydrolyzed R + .. - H2O :N N N: - Ph3P N Ph3P N: Ph3P O H2N + .. Ph3P: R R R -N2 .. .. N N N N Ph P :N R 3 + .. - Ph3P N R cis Gololobov, Y G.; Kasukhin, L. F. Tetrahedron 1992, 48, 1353. The Staudinger Reaction of Azides ■ The Staudinger ligation takes place under physiological conditions protein O pH 7 O OMe .. N N - H O .. N .. 2 H N reporter PPh2 + reporter P O Ph Ph O OMe .. N -N2 reporter +P - Ph2 Bertozzi, C. R.; et al. JACS 2005, 127, 2686. The Wittig Reaction - Review + ■ Makes C=C bonds from O PPh3 O PPh3 O PPh3 C=O : R' R - R' R R' R phosphonium ylide transition state draw as ■ Concerted [2+2], b u t th e C- concerted C bond forms slightly before the P- δ- H O CH3 H O C CH O bond. 1% 44% 3 bond bond .. R3P C H Restrepo-Cossio, A. A.; et al. P H + - Heteroat. Chem. 1997, 8, 557. δ+ R R ■ P=O elimination: above -20 °C if R = alkyl, O PPh3 O PPh3 < -20 °C below -20 °C if R = EWG CO2Et R CO2Et R ■ Making phosphonium ylides .. CH - .. Br- CH3 2 CH2 CH3-Br + n-BuLi + Ph P Ph P Ph P Ph Ph P Ph C H Ph Ph Ph 6 6 Ph ether, rt Ph Ph rt, 2 days pKa 18 this res. struct. not very useful.
Load more

Recommended publications
  • Synthetic Routes to Bromo-Terminated Phosphonate Films and Alkynyl Pyridine Compounds for Click Coupling
    University of Mary Washington Eagle Scholar Student Research Submissions Spring 5-7-2018 Synthetic Routes to Bromo-Terminated Phosphonate Films and Alkynyl Pyridine Compounds for Click Coupling Poornima Sunder Follow this and additional works at: https://scholar.umw.edu/student_research Part of the Biochemistry Commons Recommended Citation Sunder, Poornima, "Synthetic Routes to Bromo-Terminated Phosphonate Films and Alkynyl Pyridine Compounds for Click Coupling" (2018). Student Research Submissions. 226. https://scholar.umw.edu/student_research/226 This Honors Project is brought to you for free and open access by Eagle Scholar. It has been accepted for inclusion in Student Research Submissions by an authorized administrator of Eagle Scholar. For more information, please contact [email protected]. Synthetic Routes to Bromo-Terminated Phosphonate Films and Alkynyl Pyridine Compounds for Click Coupling Poornima Rachel Sunder Thesis submitted to the faculty of University of Mary Washington in partial fulfillment of the requirements for graduation with Honors in Chemistry (2018) ABSTRACT Click reactions are a highly versatile class of reactions that produce a diverse range of products. Copper-catalyzed azide-alkyne cycloaddition (CuAAC) click reactions require an azide and a terminal alkyne and produce a coupled product that is “clicked” through a triazole ring that can have a variety of substituents. In this work, bromo-terminated phosphonate films on copper oxide surfaces were explored as the platform for click coupling, as the terminal azide needed for the reaction can be generated through an in situ SN2 reaction with a terminal bromo group. The reactions were characterized using model reactions in solution before being conducted on modified copper oxide surfaces.
    [Show full text]
  • Catalytic Ethylene Dimerization and Oligomerization Speiser Et Al
    Acc. Chem. Res. 2005, 38, 784-793 reaktion)2 of ethylene, nickel salts could modify the nature Catalytic Ethylene Dimerization of the products from R-olefins to 1-butene. This phenom- and Oligomerization: Recent enon became known in the literature as ªthe nickel effectº1,3 and led to the discovery of the ªZiegler catalysisº4 Developments with Nickel and to the remarkable chemistry developed by Wilke and 5 others over decades. The selective synthesis of C4-C20 Complexes Containing linear R-olefins has become a topic of considerable P,N-Chelating Ligands interest in both academia and industry owing to their growing demand most notably as comonomers with ² ,² FREDY SPEISER, PIERRE BRAUNSTEIN,* AND ethylene [C4-C8 to yield branched linear low-density LUCIEN SAUSSINE³ polyethylene (LLDPE) with impressive rheological and Laboratoire de Chimie de Coordination (UMR 7513 CNRS), mechanical properties6], for the synthesis of poly-R-olefins Universite Louis Pasteur, 4 rue Blaise Pascal, F-67070 and synthetic lubricants (C ), as additives for high-density Strasbourg CeÂdex, France, and Institut Franc¸ais du PeÂtrole, 10 Direction Catalyse et SeÂparation, IFP-Lyon, BP 3, F-69390 polyethylene production and for the production of plas- 7-9 Vernaison, France ticizers (C6-C10) and surfactants (C12-C20). The annual 8 Received February 14, 2005 worldwide consumption of polyolefins is close to 10 tons. Because the demand for linear R-olefins is growing faster - × 6 ABSTRACT in the C4 C10 range (a ca. 2.5 10 tons/year market) than Catalytic ethylene oligomerization represents a topic of consider- in the C12+ range, the selective formation from ethylene able current academic and industrial interest, in particular for the of specific shorter chain R-olefins, which could circumvent R - production of linear -olefins in the C4 C10 range, whose demand the typical, broad Schulz-Flory distributions observed in is growing fast.
    [Show full text]
  • When Phosphosugars Meet Gold: Synthesis and Catalytic Activities of Phostones and Polyhydroxylated Phosphonite Au(I) Complexes
    Article When Phosphosugars Meet Gold: Synthesis and Catalytic Activities of Phostones and Polyhydroxylated Phosphonite Au(I) Complexes Gaëlle Malik, Angélique Ferry and Xavier Guinchard * Received: 23 September 2015 ; Accepted: 20 November 2015 ; Published: 27 November 2015 Academic Editor: Bimal Banik Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, 1 Avenue de la Terrasse, 91198 Gif sur Yvette cedex, France; [email protected] (G.M.); [email protected] (A.F.) * Correspondence: [email protected]; Tel.: +33-1-69-82-30-66 Abstract: The synthesis and characterization of P-chiral phosphonite-, phosphonate- and thiophosphonate-Au(I) complexes are reported. These novel ligands for Au(I) are based on glycomimetic phosphorus scaffolds, obtained from the chiral pool. The catalytic activities of these complexes are shown in the cyclization of allenols and the hydroamination of 2-(2-propynyl)aniline combined with an organocatalyzed reduction to the corresponding 2-phenyl tetrahydroquinoline. All described gold complexes present excellent catalytic activities. Keywords: gold catalysis; phosphosugars; catalysis; heterocycles; P-stereogeny 1. Introduction One of the major advances of the 21th century in organic chemistry is undoubtedly the increased importance of gold catalysis. Long believed to be useless for catalysis, gold complexes have emerged as powerful tools for the catalysis of myriads of reactions [1–9]. In particular, the gold tolerance towards air, moisture and numerous chemical functionalities renders the use of these catalysts very convenient. However, the bicoordinate linear geometry of gold(I) complexes makes the control of the asymmetry difficult, the chiral ligand being placed in a distal position to the reactive cationic center.
    [Show full text]
  • Phosphorus-Containing Amino Acids with a P–C Bond in the Side Chain Or a P–O, P–Sorp–N Bond: Cite This: RSC Adv., 2020, 10, 6678 from Synthesis to Applications
    RSC Advances View Article Online REVIEW View Journal | View Issue Phosphorus-containing amino acids with a P–C bond in the side chain or a P–O, P–SorP–N bond: Cite this: RSC Adv., 2020, 10, 6678 from synthesis to applications a b b Mathieu Arribat, Florine Cavelier * and Emmanuelle Remond´ * Since the discovery of (L)-phosphinothricin in the year 1970, the development of a-amino acids bearing a phosphorus group has been of renewed interest due to their diverse applications, including their use in [18F]-fluorolabeling, as fluorescent probes, as protecting groups and in the reversible immobilization of amino acids or peptide derivatives on carbon nanomaterials. Considerable progress has also been achieved in the field of antiviral agents, through the development of phosphoramidate prodrugs, which increase significantly the intracellular delivery of nucleoside monophosphate and monophosphonate analogues. This review aims to summarize the strategies reported in the literature for the synthesis of P(III), P(IV) and P(V) phosphorus-containing amino acids with P–C, P–O, P–SorP–N bonds in the side Received 2nd December 2019 Creative Commons Attribution-NonCommercial 3.0 Unported Licence. chains and their related applications, including their use in natural products, ligands for asymmetric Accepted 22nd January 2020 catalysis, peptidomimetics, therapeutic agents, chemical reagents, markers and nanomaterials. The DOI: 10.1039/c9ra10917j discussion is organized according to the position of the phosphorus atom linkage to the amino acid side rsc.li/rsc-advances chain, either in an a-, b-, g-ord-position or to a hydroxyl, thiol or amino group. 1. Introduction phosphinothricin has engendered the development of numerous drugs for neurodegenerative disease treatment.
    [Show full text]
  • Some Transition Metal Complexes of Trivalent Phosphorus Esters
    AN ABSTRACT OF THE THESIS OF HARRY VAUGHN STUDER for the MASTER OF SCIENCE (Name) (Degree) inCHEMISTRY (Inorganic) presented on ///( (Major) / (Date') Title: SOME TRANSITION METAL COMPLEXES OF TRIVALENT PHOSPHORUS ESTERS Redacted for Privacy Abstract approved: Dr. In T. Yoke r The ligands in the series EtnP(OEt)3_11, n = 0 - 3,all form pseudotetrahedral high-spin bis -complexes with cobalt (II) chloride. Magnetic, spectrophotometric, conductivity, and molecular weight data show that the phosphorus ester ligands (but not the phosphine) also form five-coordinate low-spin tris-complexes; these can be isolated with the phosphonite and phosphinite ligands, while the existence of the tris -phosphite is marginal.At cobalt (II) to phosphorus ester mole ratios of 1:2, a mixture of species is present in all cases.All are non-conducting in nitrobenzene. The ester complexes are much more susceptible to autoxidation than is the phosphine complex. Some Transition Metal Complexes of Trivalent Phosphorus Esters by Harry Vaughn Studer A THESIS submitted to Oregon State University in partial fulfillment of the requirements for the degree of Master of Science June 1972 APPROVED: Redacted for Privacy Profes of Chemi str y / in crge of major Redacted for Privacy Head of Department of Chemistry Redacted for Privacy Dean of Graduate School Date thesis is presented Typed by Donna Olson f arry Vatighn Studer ACKNOWLEDGEMENTS The author wishes to thank his research advisor, Dr. John T. Yoke, for his expert direction of this research, for his patience, and for the opportunity of learning through association with him. Acknowledgement is made to the donors of the Petroleum Re- search Fund, administered by the American Chemical Society, for the support of this work.
    [Show full text]
  • Asymmetric Synthesis of Organophosphates and Their
    ASYMMETRIC SYNTHESIS OF ORGANOPHOSPHATES AND THEIR DERIVATIVES Thesis Submitted to The College of Arts and Sciences of the UNIVERSITY OF DAYTON In Partial Fulfillment of the Requirements for The Degree of Master of Science in Chemistry By Batool J. Murtadha Dayton, Ohio May 2020 ASYMMETRIC SYNTHESIS OF ORGANOPHOSPHATES AND THEIR DERIVATIVES Name: Murtadha, Batool J. APPROVED BY: __________________________________ Jeremy Erb, Ph.D. Research Advisor Assistant Professor Department of Chemistry University of Dayton ___________________________________ Vladimir Benin, Ph.D. Professor of Chemistry Department of Chemistry University of Dayton ___________________________________ Justin C. Biffinger, Ph.D. Committee Member Assistant Professor Department of Chemistry University of Dayton ii © Copyright by Batool J. Murtadha All rights reserved 2020 iii ABSTRACT ASYMMETRIC SYNTHESIS OF ORGANOPHOSPHATES AND THEIR DERIVATIVES Name: Murtadha, Batool J. University of Dayton Advisor: Dr. Jeremy Erb Organophosphorus compounds (OPs) are widely used in the agricultural industry especially in the pesticide market. Phosphates play a huge role as biological compounds in the form of energy carrier compounds like ATP, and medicine as antivirals. OPs have become increasingly important as evidenced by the publication of new methods devoted to their uses and synthesis. These well-established studies lay the basis for industrial organic derivatives of phosphorus preparations. The current work explored methods of synthesizing chiral organophosphate triesters. We experimented with different processes roughly divided into either an electrophilic or nucleophilic strategy using chiral Lewis acids, organocatalysts (HyperBTM), activating agents, and chiral auxiliaries with the goal of control stereoselectivity. These methods were explored through the use of different starting materials like POCl3, triethyl phosphate, methyl phosphordichloradate, and PSCl3.
    [Show full text]
  • Qsar Analysis of the Chemical Hydrolysis of Organophosphorus Pesticides in Natural Waters
    QSAR ANALYSIS OF THE CHEMICAL HYDROLYSIS OF ORGANOPHOSPHORUS PESTICIDES IN NATURAL WATERS. by Kenneth K. Tanji Principal Investigator and Jonathan 1. Sullivan Graduate Research Assistant Department of Land, Air and Water Resources University of California, Davis Technical Completion Report Project Number W-843 August, 1995 University of California Water Resource Center The research leading to this report was supported by the University of California Water Resource Center as part of Water Resource Center Project W-843. Table of Contents Page Abstract 2 Problem and Research Objectives 3 Introduction 5 Theoretical Background 6 QSAR Methodology 7 Molecular Connectivity Theory 8 Organophosphorus Pesticides 12 Experimental Determination of Rates 15 Results and Discussion 17 Principal Findings and Significance 19 References 34 List of Tables Page Table 1. Statistical relationship between OP pesticides and first-order MC/'s. 30 Table 2. Inherent conditions of waters used in experimental work. 16 Table 3. Estimated half-lives for organophosphorus esters derived from model. 31 Table 4. Half-lives and first-order MCI' sfor model calibration data set. 31 Table 5. Experimental kinetic data for validation set compounds, Sacramento. 33 List of Figures Page Figure 1. Essential Features OfQSAR Modeling Methodology. 21 Figure 2. Regression plot for In hydrolysis rate vs. 1st order MCl' s. 22 Figure 3. a 3-D molecular model, a line-segment model and a graphical model. 23 Figure 4. Molecular connectivity index suborders. 24 Figure 5. Chlorpyrifos and its fourteen fourth order path/cluster fragments. 25 Figure 6. Abridged MClndex output. 26 Figure 7. Parent acids of most common organophosphorus pesticides. 12 Figure 8.
    [Show full text]
  • Applications of Boronic Acids in Organic Synthesis
    Applications of Boronic Acids in Organic Synthesis A dissertation presented by Pavel Starkov in partial fulfilment of the requirements for the award of the degree of DOCTOR OF PHILOSOPHY at UNIVERSITY COLLEGE LONDON Department of Chemistry Christopher Ingold Laboratories University College London 20 Gordon Street WC1H 0AJ London Declaration This dissertation is the result of my own work. Where information has been derived from other sources it has been clearly indicated so and acknowledged accordingly. /Pavel Starkov/ ii Abstract This thesis describes progress on the application of boronic acids and borate esters as catalysts and reagents in synthetic organic synthesis, focusing on two areas: one-pot enolate formation/aldol reactions and amide bond formation. Chapter 1 introduces the reader to boronic acids and derivatives thereof, their methods of preparation and their use in synthetic organic chemistry as reactants, reagents and catalysts. Chapter 2 covers current chemical methods and cellular alternatives for amide bond formation. Here, we also discuss our use of boron reagents for the activation of carboxylic acids as well as amides. Chapter 3 introduces a new concept in catalytic aldol reactions, i.e. an alternative strategy to access boron enolates in situ. The work covers successful demonstration of the feasibility of such an approach on an intramolecular system. A novel variation of aerobic Chan–Evans– Lam coupling, an intramolecular coupling of an aliphatic alcohol with a boronic acid using catalytic copper, is also introduced Chapter 4 builds on our observations on gold catalysis and especially that in relation to electrophilic halogenations. Chapter 5 contains full details of the experimental procedures.
    [Show full text]
  • Redox-Responsive Phosphonite Gold Complexes in Hydroamination Catalysis† Cite This: Chem
    Showcasing research from the groups of Jan Paradies As featured in: from the University of Paderborn and Frank Breher from the Karlsruhe Institute of Technology (KIT). Volume 55 Number 37 10 May 2019 Pages 5297–5396 Redox-responsive phosphonite gold complexes in ChemComm Chemical Communications hydroamination catalysis rsc.li/chemcomm Very high activities were observed in the redox-induced hydroamination of alkynes by employing a redox-active gold(I) complex featuring a phosphonite-based ligand. Very low catalyst loadings (down to 10 ppm) and very mild conditions (25 °C) were used. ISSN 1359-7345 COMMUNICATION Kotaro Satoh, Masami Kamigaito et al . Cooperative reduction of various RAFT polymer terminals using hydrosilane and thiol via polarity reversal catalysis See Jan Paradies, Frank Breher et al ., Chem . Commun ., 2019, 55 , 5323. rsc.li/chemcomm Registered charity number: 207890 ChemComm View Article Online COMMUNICATION View Journal | View Issue Redox-responsive phosphonite gold complexes in hydroamination catalysis† Cite this: Chem. Commun., 2019, 55,5323 Eva Deck,a Hanna E. Wagner,a Jan Paradies *b and Frank Breher *a Received 21st February 2019, Accepted 20th March 2019 DOI: 10.1039/c9cc01492f rsc.li/chemcomm Very high activities were observed in the redox-induced hydroamination important structural features of these ligands is the weak – of alkynes by employing a redox-active gold(I)complexfeaturingan for catalyst stability nonetheless crucial – arene p-interactions electron-deficient, terphenyl-substituted phosphonite-based ligand. with the metal centre. In recent years, elegant variations of The hydroamination proceeds roughly two-fold faster with the in situ Buchwald-type biaryl phosphines have been reported by various 7–10 Creative Commons Attribution 3.0 Unported Licence.
    [Show full text]
  • Metal Complexes As Catalysts for the Synthesis of Heterocycles
    METAL COMPLEXES AS CATALYSTS FOR THE SYNTHESIS OF HETEROCYCLES Steven Lal Department of Chemistry, Imperial College London A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Imperial College London May 2013 1 Declaration I certify that all the work in this thesis is solely my own, except where explicitly stated and appropriately referenced. No part of the thesis has been submitted previously for a degree at this, or any other, university. 2 Copyright Notice Imperial College of Science, Technology and Medicine Department Of Chemistry Metal Complexes as Catalysts for the Synthesis of Heterocycles © 2013 Steven Lal [email protected] The copyright of this thesis rests with the author and is made available under a Creative Commons Attribution Non-Commercial No Derivatives License. Researchers are free to copy, distribute or transmit the thesis on the condition that they attribute it, that they do not use it for commercial purposes and that they do not alter, transform or build upon it. For any reuse or redistribution, researchers must make clear to others the license terms of this work. Steven Lal Department of Chemistry Imperial College London Exhibition Road London SW7 2AZ UK www.imperial.ac.uk 3 Contents Abstract ...................................................................................................................................... 8 Acknowledgements .................................................................................................................
    [Show full text]
  • H-Phosphonates: Versatile Synthetic Precursors to Biologically Active Phosphorus Compounds*
    Pure Appl. Chem., Vol. 79, No. 12, pp. 2217–2227, 2007. doi:10.1351/pac200779122217 © 2007 IUPAC H-Phosphonates: Versatile synthetic precursors to biologically active phosphorus compounds* Adam Kraszewski1,‡ and Jacek Stawinski1,2,‡ 1Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland; 2Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, S-10691 Stockholm, Sweden Abstract: In this review, a short account of H-phosphonate chemistry and its application to the synthesis of biologically important phosphates and their analogs is given. Keywords: H-phosphonates; phosphate analogs; biological activity; nucleic acids; drugs. INTRODUCTION Located at the crossroad of various bioinformation exchange pathways, phosphorus-containing com- pounds play a key role in living organisms as carriers of genetic information and important signalling, regulatory, energy transfer, and structural compounds [1]. Due to this pivotal role, biologically impor- tant phosphorus compounds have become therapeutic targets in various modern medicinal techniques, such as antisense [2] and antigene [3] approaches to modulation gene expression, or a gene silencing technique using short interfering RNA (siRNA) [4]. To maximize the desired biological effect and to minimize cytotoxicity, a biologically active com- pound has to have very precisely adjusted chemical and pharmacokinetic properties. This can be achieved by, e.g., changing pKa values of the ionizeable functions, changing electronegativity of the substituents, their size, hydrophobicity, etc. These features can also influence transport of a drug across cell membranes, its preferential degradation in normal or activation in the neoplastic or virus-infected cells, and can contribute to the overall efficiency of the drug. A prominent example here are antiviral pronucleotides in which the phosphate moiety is masked with alkyl or aryl groups that are removed chemically and enzymatically in cells to produce an active antiviral nucleotide [5].
    [Show full text]
  • The Hydrolysis of Phosphinates and Phosphonates: a Review
    molecules Review The Hydrolysis of Phosphinates and Phosphonates: A Review Nikoletta Harsági and György Keglevich * Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1521 Budapest, Hungary; [email protected] * Correspondence: [email protected]; Tel.: +36-1-463-1111 (ext. 5883) Abstract: Phosphinic and phosphonic acids are useful intermediates and biologically active com- pounds which may be prepared from their esters, phosphinates and phosphonates, respectively, by hydrolysis or dealkylation. The hydrolysis may take place both under acidic and basic conditions, but the C-O bond may also be cleaved by trimethylsilyl halides. The hydrolysis of P-esters is a challenging task because, in most cases, the optimized reaction conditions have not yet been explored. Despite the importance of the hydrolysis of P-esters, this field has not yet been fully surveyed. In order to fill this gap, examples of acidic and alkaline hydrolysis, as well as the dealkylation of phosphinates and phosphonates, are summarized in this review. Keywords: hydrolysis; dealkylation; phosphinates; phosphonates; P-acids 1. Introduction Phosphinic and phosphonic acids are of great importance due to their biological activity (Figure1)[ 1]. Most of them are known as antibacterial agents [2,3]. Multidrug- resistant (MDR) and extensively drug-resistant (XDR) pathogens may cause major problems Citation: Harsági, N.; Keglevich, G. in the treatment of bacterial infections. However, Fosfomycin has remained active against The Hydrolysis of Phosphinates and both Gram-positive and Gram-negative MDR and XDR bacteria [2]. Acyclic nucleoside Phosphonates: A Review. Molecules phosphonic derivatives like Cidofovir, Adefovir and Tenofovir play an important role 2021, 26, 2840.
    [Show full text]