DOCSLIB.ORG

(19) United States (12) Patent Application Publication (10) Pub

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(19) United States (12) Patent Application Publication (10) Pub US 20090069569Al (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0069569 A1 Nolan et al. (43) Pub. Date: Mar. 12, 2009 (54) CYCLOADDITION OF AZIDES AND Related US. Application Data ALKYNES (60) Provisional application No. 60/971,779, ?led on Sep. 12, 2007. (75) Inventors: Steven P. Nolan, Tarragona (ES); Silvia Diez-Gonzalez, Publication Classi?cation Barakaldo-Vizcaya (ES) (51) Int. C1. 0070 249/04 (2006.01) Correspondence Address: (52) us. c1. ...................................................... .. 548/255 McGLINCHEY STAFFORD, PLLC (57) ABSTRACT Attn: IP Group 301 Main Street, 14th Floor This invention provides a process Which comprises contact BATON ROUGE, LA 70802 (US) ing, in a reaction Zone, at least one organic aZide, at least one alkyne, and at least one N-heterocyclic carbene copper com pound in Which the ligands are either (i) a halide and an (73) Assignees: Institut Catala d’Investigacio N-heterocyclic carbene or (ii) tWo N-heterocyclic carbenes Quimica, Tarragona (ES); and a BF; or PF; anion, to form a l,2,3-triaZole in Which at Institucio Catalana de Recerca i least the l and 4 positions each has a substituent. The N-het Estudis Avancats, Barcelona (ES) erocyclic carbene either an imidaZol-2-ylidene in Which the l and the 3 positions each has a substituent Which has at least (21) Appl. No.: 12/209,323 one carbon atom, or a 4,5-dihydro-imidaZol-2-ylidene in Which the l and the 3 positions each has a substituent Which (22) Filed: Sep. 12, 2008 has at least one carbon atom. US 2009/0069569 A1 Mar. 12, 2009 CYCLOADDITION OF AZIDES AND triaZole in Which at least the 1 and 4 positions each has a ALKYNES substituent. The N-heterocyclic carbene is either an imidaZol 2-ylidene in Which the 1 and the 3 positions each has a REFERENCE TO RELATED APPLICATION substituent Which has at least one carbon atom, or a 4,5 [0001] This application claims priority from US. Applica dihydro-imidaZol-2-ylidene in Which the 1 and the 3 positions tion No. 60/971,779, ?led Sep. 12, 2007, the disclosure of each has a substituent Which has at least one carbon atom. Which is incorporated herein by reference. [0006] These and other features of this invention Will be still further apparent from the ensuing description and TECHNICAL FIELD appended claims. [0002] This invention relates to copper-catalyzed cycload FURTHER DETAILED DESCRIPTION OF THE dition of aZides and alkynes. INVENTION BACKGROUND [0007] Throughout this document, the term ‘reaction Zone’ [0003] Cycloaddition of aZides and alkynes to yield 1,2,3 means any place Where the organic aZide, alkyne, and catalyst triaZoles is a type of Huisgen cycloaddition. Most often, come together. As used throughout this document, the term catalytic systems enabling this transformation consist of a ‘catalyst’ refers to the N-heterocyclic carbene copper com copper(II) salt and a reducing agent. Metallic copper or cop pound, and the term ‘N-heterocyclic carbene copper com per clusters have also been employed. Copper(I) has also been pound’ means the copper(I) complexes in Which the ligands reported in the catalysis of this process. One report of copper are either (i) a halide and an N-heterocyclic carbene or (ii) tWo (I) catalyZed cycloaddition of aZides and terminal alkynes N-heterocyclic carbenes and a BF4_ or PE; anion. Through utilized cuprous halides in reactions in Which the alkyne Was out this document, the term “mol %” is used as an abbrevia on a support, but the reaction did not Work When both the tion for mole percent. aZide and the alkyne Were in solution; see Tomoe et al., .1. Org. [0008] The reaction in the processes of this invention can be Chem, 2002, 67, 3057-3064. Tomoe et al. reported that the represented by the folloWing equation: solution-phase reaction, using simple copper(I) salts in the presence of a nitrogen base, resulted in cross-coupling of the R N terminal alkynes, along With other by-products (J. Org. / \ Chem, 2002, 67, 3057-3064). Another report of copper(I) \N \N catalysis of cycloadditions of aZides and terminal alkynes employed copper(I) generated in situ from copper(II) salts, see Rostovtsev et al., Angew. Chemie Int. Ed. EngL, 2002,41, 2596-2599. In the above equation, When R":H, the alkyne is a terminal SUMMARY OF THE INVENTION alkyne. The reaction shoWn in the equation takes place in the [0004] Pursuant to this invention, cycloaddition of organic presence of a N-heterocyclic carbene copper compound in aZides and alkynes to form 1,2,3-triaZoles is provided. Sur Which the ligands are either (i) a halide and an N-heterocyclic prisingly, internal alkynes as Well as terminal alkynes can be carbene or (ii) tWo N-heterocyclic carbenes and a BF4_ or used to form such cycloaddition products. When a terminal PE; anion. A solvent is optional for the above reaction. The alkyne is used, a 1,4-substituted 1,2,3-triaZole is obtained, R, R', and R" groups, as Well as the N-heterocyclic carbene and When an internal alkyne is used, a 1,4,5-substituted 1,2, copper compounds, are as detailedbeloW. In the 1,2,3-triaZole 3-tr‘iaZole is obtained. To date, other regiochemistries have formed in the reaction, When the alkyne is a terminal alkyne, not been seen using this process, and very feW side products the 1 and 4 positions each has a substituent; the substituent at have been observed. The catalysts in the processes of this the 1 position (R) is from the aZide, and the substituent at the invention are copper(I) compounds in Which the ligands are 4 position (R') is from the terminal alkyne. For internal either (i) a halide and an N-heterocyclic carbene or (ii) tWo alkynes, in the 1,2,3-triaZole formed in the reaction, the 1, 4 N-heterocyclic carbenes and a BF4_ or PE; anion. The pro and 5 positions each has a substituent; the substituent at the 1 cesses of this invention are robust to many types of solvents, position (R) is from the aZide, and the substituents at the 4 (R') including Water, and the processes can be conducted in the and 5 (R") positions are from the internal alkyne. absence of ancillary solvent. Another advantage is that the [0009] The types of organic aZides employed in this inven presence of oxygen is not detrimental to the processes of this tion include alkyl aZides, ether aZides, aryl aZides, and aralkyl invention. The processes of this invention are considered to aZides. One or more functional groups, including cyano fall under the umbrella of “click” chemistry, reactions in groups and nitro groups, may be present in an aryl aZide, in an Which carbon-heteroatom-carbon links are made, With such aralkyl aZide, or in an alkyl aZide. The alkyl portion of the reactions being stereospeci?c, insensitive to oxygen and alkyl aZides can be a branched, straight chain, or cyclic group. Water, and able to produce high yields of the product. For Typically, the alkyl aZides have one to about ?fteen carbon further details on “click” chemistry, see Kolb et al., Angew. atoms, and preferably about three to about ten carbon atoms. Chemie Int. Ed. EngL, 2001, 40, 2004-2021. In the etheric portion of an ether aZide, there can be more than [0005] An embodiment of this invention is a process Which one ether linkage. Ether aZides generally have about three to comprises contacting, in a reaction Zone, at least one organic about ?fteen carbon atoms, and preferably about ?ve to about aZide, at least one alkyne, and at least one N-heterocyclic ten carbon atoms. Preferred types of aZides include aryl carbene copper compound in Which the ligands are either (i) aZides and aralkyl aZides. Mixtures of any tWo or more a halide and an N-heterocyclic carbene or (ii) tWo N-hetero organic aZides can be used, if desired. The use of mixtures of cyclic carbenes and a BF4_ or PE; anion, to form a 1,2,3 organic aZides Will yield a mixture of triaZoles. US 2009/0069569 A1 Mar. 12, 2009 [0010] Suitable alkyl aZides include, but are not limited to, the alkali metal aZide (e.g., about 1.01 to about 1.10 moles of methyl aZide, ethyl aZide, n-propyl aZide, isopropyl aZide, alkali metal aZide per mole of organic halide) is preferred. cyclopropyl aZide, 3-cyanopropyl aZide, n-butyl aZide, sec [0017] Both terminal alkynes and internal alkynes can be butyl aZide, tert-butyl aZide, cyclobutyl aZide, 4-cyanobutyl used in the practice of this invention; both types of alkyne can aZide, pentyl aZide, 3-cyanopentyl aZide, cyclopentyl aZide, 2,2-dimethylpropyl aZide, hexyl aZide, cyclohexyl aZide, contain functional groups. Suitable functional groups in these 4-cyanocyclohexyl aZide, methylcycxlohexyl aZide, heptyl alkynes include carbon-carbon double bonds, ether groups, aZide, octyl aZide, cyclooctyl aZide, nonyl aZide, and decyl ester groups, ketyl groups, hydroxyl groups, chlorine atoms, aZide. Preferred alkyl aZides include methyl aZide, 3-cyano ?uorine atoms, trihydrocarbylsilyl groups, nitrogen atoms propyl aZide, and heptyl aZide. It is noted that methyl aZide, (e.g., as amino groups), and the like. In the practice of this ethyl aZide, and n-propyl aZide are quite explosive, and thus invention, terminal alkynes typically have three to about care should be exercised in their handling. tWenty carbon atoms, and preferably about ?ve to about [0011] Examples of ether aZides that can be used in the tWelve carbon atoms. When expressed as RCECH, groups R practice of this invention include 3,3-dimethoxypropyl aZide, that may be part of a terminal alkyne in this invention include 3,3-diethoxypropyl aZide, 4-butyloxybutyl aZide, 4-propoxy alkyl groups (straight chain, cyclic, or, preferably, branched), pentyl aZide, 5-methoxyhexyl aZide, 4-(2 -tetrahydrofuranyl) alkenyl groups (straight chain, branched, or, preferably, butyl aZide, 2-[2-(1,3-dioxolanyl)]-ethyl aZide, 2-[2-(1,3-di cyclic), aryl groups, and silyl groups.
Load more

Recommended publications
  • Synthesis and Consecutive Reactions of Α-Azido Ketones: a Review
    Molecules 2015, 20, 14699-14745; doi:10.3390/molecules200814699 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Synthesis and Consecutive Reactions of α-Azido Ketones: A Review Sadia Faiz 1,†, Ameer Fawad Zahoor 1,*, Nasir Rasool 1,†, Muhammad Yousaf 1,†, Asim Mansha 1,†, Muhammad Zia-Ul-Haq 2,† and Hawa Z. E. Jaafar 3,* 1 Department of Chemistry, Government College University Faisalabad, Faisalabad-38000, Pakistan, E-Mails: [email protected] (S.F.); [email protected] (N.R.); [email protected] (M.Y.); [email protected] (A.M.) 2 Office of Research, Innovation and Commercialization, Lahore College for Women University, Lahore-54600, Pakistan; E-Mail: [email protected] 3 Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, Serdang-43400, Selangor, Malaysia † These authors contributed equally to this work. * Authors to whom correspondence should be addressed; E-Mails: [email protected] (A.F.Z.); [email protected] (H.Z.E.J.); Tel.: +92-333-6729186 (A.F.Z.); Fax: +92-41-9201032 (A.F.Z.). Academic Editors: Richard A. Bunce, Philippe Belmont and Wim Dehaen Received: 20 April 2015 / Accepted: 3 June 2015 / Published: 13 August 2015 Abstract: This review paper covers the major synthetic approaches attempted towards the synthesis of α-azido ketones, as well as the synthetic applications/consecutive reactions of α-azido ketones. Keywords: α-azido ketones; synthetic applications; heterocycles; click reactions; drugs; azides 1. Introduction α-Azido ketones are very versatile and valuable synthetic intermediates, known for their wide variety of applications, such as in amine, imine, oxazole, pyrazole, triazole, pyrimidine, pyrazine, and amide alkaloid formation, etc.
    [Show full text]
  • Tracking of Bacterial Metabolism with Azidated Precursors and Click- Chemistry”
    Tracking of bacterial metabolism with azidated precursors and click-chemistry Dissertation zur Erlangung des Doktorgrades der Naturwissenschaften vorgelegt beim Fachbereich für Biowissenschaften (15) der Johann Wolfang Goethe Universität in Frankfurt am Main von Alexander J. Pérez aus Nürnberg Frankfurt am Main 2015 Dekanin: Prof. Dr. Meike Piepenbring Gutachter: Prof. Dr. Helge B. Bode Zweitgutachter: Prof. Dr. Joachim W. Engels Datum der Disputation: 2 Danksagung Ich danke meinen Eltern für die stete und vielseitige Unterstützung, deren Umfang ich sehr zu schätzen weiß. Herrn Professor Dr. Helge B. Bode gilt mein besonderer Dank für die Übernahme als Doktorand und für die Gelegenheit meinen Horizont in diesen mich stets faszinierenden Themenbereich in dieser Tiefe erweitern zu lassen. Seine persönliche und fachliche Unterstützung bei der Projektwahl und der entsprechenden Umsetzung ist in dieser Form eine Seltenheit und ich bin mir dieser Tatsache voll bewusst. Gerade die zusätzlich erworbenen Kenntnisse im Bereich der Biologie, sowie der Wert interdisziplinärer Zusammenarbeit ist mir durch zahlreiche freundliche und wertvolle Mitglieder der Arbeitsgruppe bewusst geworden und viele zündenden Ideen wären ohne sie womöglich nie aufgekommen. Einen besonderen Dank möchte ich in diesem Kontext Wolfram Lorenzen und Sebastian Fuchs, die gerade in der Anfangszeit eine große Hilfe waren, ausdrücken. Dies gilt ebenso für die „N100-Crew“ und sämtliche Freunde, die in dieser Zeit zu mir standen und diesen Lebensabschnitt unvergesslich gemacht haben.
    [Show full text]
  • Triphenylphosphine Phenylimide 의 전기화학적인 환원 Electrochemical
    DAEHAN HWAHAK HWOEJEE (Journal of the Korean Chemical Society) Vol. 18, No. 5, 1974 Printed in Republic of Korea Triphenylphosphine Phenylimide 의 전기화학적인 환원 朴鍾民* , Wilson M. Gulick, Jr. 미국 후로리다주립대학교 화학과 (1974. 7. 13 접수 ) Electrochemical Reduction of Triphenylphosphine Phenylimide Chong Min *Pak and Wilson M. Gulick, Jr. Department of Chemistry^ Floridia State University^ Tallahassee, Florida 32306, U, S. A. 요 약 . Triphenylphosphine phenylimid合의 비수용액에서의 전기화학적인 환원반응을 polaro- graphy, cyclic voltammetry, controlled-potential coulometry 및 electron spin resonance 법 을 써 서 고 찰하였다 . 이 유기 인화합물은 cme-electon transfer 에 따라서 anion radical 형성되 나 순간일 뿐이 고 protonation 과 재차 one-electon reduction 결과 인과 질소사이의 이중결합이 끊어진다 . 그 결과 아 닐린이 주요 반응생성물로서 발견되었다 . 또 한편 동반하는 화학반응결과 생긴 주산물의 하나인 triphenylposphine oxide 의 환원결과 인과 페닐사이의 단일결합이 끊어지는 것도 관찰할 수 있었다 . Abstract. The electrochemical reduction of triphenylphosphine penylimide in nonaqueous media has been examined by polarography, cyclic voltammetry, controlled-potential coulometry and electron spin resonance spectroscopy. The reduction of tiiphe교 ylphosphine phenylimide proceeds by a one- electron transfer to form anion radical which undergoes both protonation and a second one-electron reduction followed by cleavage of the phosphorus-nitrogen double bond. Aniline is a major product. The cleavage of a phosphours-phenyl bond was also observed after reduction of triphenylphosphine oxide which is one of the major products of the chemical reaction which follow the primary process. synthesis and ligands in coordination chemistry. 1. Introduction The range of application of phosphorus com­ Phosphorus compounds have become increas­ pounds in modern technology is extremely broad ingly important as intermediates in organic and varied.
    [Show full text]
  • Mediated Azide-Alkyne Cycloaddition Reactions Using Chelating Azides Wendy S
    Florida State University Libraries Electronic Theses, Treatises and Dissertations The Graduate School 2012 Development of Copper(II)-Mediated Azide-Alkyne Cycloaddition Reactions Using Chelating Azides Wendy S. Brotherton Follow this and additional works at the FSU Digital Library. For more information, please contact [email protected] THE FLORIDA STATE UNIVERSITY COLLEGE OF ARTS AND SCIENCES DEVELOPMENT OF COPPER(II)-MEDIATED AZIDE-ALKYNE CYCLOADDITION REACTIONS USING CHELATING AZIDES By WENDY S. BROTHERTON A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy Degree Awarded: Spring Semester, 2012 Wendy S. Brotherton defended this dissertation on December 8, 2011. The members of the supervisory committee were: Lei Zhu Professor Directing Dissertation P. Bryant Chase University Representative Gregory B. Dudley Committee Member Igor V. Alabugin Committee Member Michael G. Roper Committee Member The Graduate School has verified and approved the above-named committee members, and certifies that the dissertation has been approved in accordance with university requirements. ii This manuscript is dedicated to my mother for all of her encouragement and sacrifices over the many years of my education. I would also like to dedicate this to my fiancé, Travis Ambrose, who has been so supportive and encouraging throughout this entire process. iii ACKNOWLEDGEMENTS I would like to thank Professor Lei Zhu for his guidance, support and assistance over the course of my graduate studies. I would like to express my gratitude to the past and present members of the Zhu group for their support and friendship over the years: Dr.
    [Show full text]
  • Synthetic Approaches to Heterocyclic Bicyclo[2.1.0]Pentanes
    SYNTHETIC APPROACHES TO HETEROCYCLIC BICYCLO[2.1.0]PENTANES Rabah N. Alsulami A THESIS Submitted to the Graduate College of Bowling Green State University in partial fulfillment of The requirements for the degree of MASTER OF SCIENCE August 2011 Committee: Thomas H. Kinstle (Advisor) Marshall Wilson Alexander N. Tarnovsky ABSTRACT Thomas H. Kinstle, Advisor Bicyclic systems such as bicyclo[2.1.0]pentanes and 5-oxabicyclo[2.1.0]pentanes are known to display a variety of unique chemical properties associated with their high strain energy. To the best of our knowledge, there were no reports regarding synthesis and investigation of 5- azabicyclo[2.1.0]pentanes. Therefore, the initial goal of this research was synthesis of 5-azabicyclo[2.1.0]pentane and investigation of its chemical properties. The cycloaddition reaction of azides (58, 59, 61) to olefins (54, 55) with further elimination of nitrogen was chosen as a synthetic method in order to obtain the compounds of interest. Starting olefins (3,3-dimethyl-1-cyclobutene-1-carboxylic acid (54) and methyl 3,3-dimethyl-1-cyclobutene-1-carboxylate (55) and azides phenyl azide (58), p- toluenesulfonyl azide (59), and picryl azide (61) were successfully synthesized and characterized by NMR spectroscopy and GCMS spectrometry. The addition reaction between azides and olefins was performed under various conditions, such as different solvents and temperature; however, according to NMR spectroscopy and GCMS spectrometry, olefins (54, 55) do not undergo cycloaddition reaction with azides (58, 59, 61). In order to investigate that behavior, cycloaddition reactions of more reactive olefins (66, 68) with azides (58, 59, 61) were performed under a variety of conditions.
    [Show full text]
  • Base-Catalyzed Synthesis of Aryl Amides from Aryl Azides and Aldehydes
    Electronic Supplementary Material (ESI) for Chemical Science. This journal is © The Royal Society of Chemistry 2015 SUPPORTING INFORMATION Base-Catalyzed Synthesis of Aryl Amides from Aryl Azides and Aldehydes Sheng Xie,aYang Zhang,a Olof Ramström,*,a and Mingdi Yan*,a,b aDepartment of Chemistry, KTH - Royal Institute of Technology, Teknikringen 36, S-10044 Stockholm, Sweden bDepartment of Chemistry, University of Massachusetts Lowell, 1 University Ave., Lowell, MA 01854, USA *E-mail: [email protected], [email protected] Table of Contents General procedures ................................................................................................................................... S1 Figure S1. 1H NMR spectra of model reaction ......................................................................................... S2 Figure S2. Azide decomposition temperatures ......................................................................................... S2 Table S1. Optimization of conditions for reaction of α-unsubstituted aldehyde with phenyl azide. ....... S3 Synthesis of azides .................................................................................................................................... S3 Synthesis of products ................................................................................................................................ S7 References .............................................................................................................................................. S16 Characterization
    [Show full text]
  • Hale Ronnie L 196812 Phd 326
    In presenting the dissertation as a partial fulfillment of the requirements for an advanced degree from the Georgia Institute of Technology, I agree that the Library of the Institute shall make it available for inspection and circulation in accordance with its regulations governing materials of this type. I agree that permission to copy from, or to publish from, this dissertation may be granted by the professor under whose direction it was written, or, in his absence, by the Dean of the Graduate Division when such copying or publication is solely for scholarly purposes and does not involve potential financial gain. It is under- stood that any copying from, or publication of, this dis- sertation which involves potential financial gain will not be allowed without written permission. 7/25/68 ,^; I lid PART I THE AZIDE-OLEFIN REACTION PART II STUDIES IN THE SYNTHESES OF EREMOPHILANE SESQUITERPENES A THESIS Presented to The Faculty of the Graduate Division by Ronnie Lee Hale In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the School of Chemistry Georgia Institute of Technology October, 1968 PART I THE AZIDE-OLEFIN REACTION PART II STUDIES IN THE SYNTHESES OF EREMOPHILANE SESQUITERPENES Approved: . A 4:Chlrmari (j im CJ Date approved by Chairman /11*-49 , 'TU11111[11.. ii ACKNOWLEDGEMENTS The author expresses gratitude to Dr. Leon H. Zalkow for his invaluable guidance and counsel during the course of this study and in preparation of this dissertation. The author also wishes to thank Drs. John R. Dyer and Drury S. Caine, III for serving as members of the read- ing committee.
    [Show full text]
  • Copper-Catalyzed Azide Alkyne Cycloaddition Polymer Networks
    COPPER-CATALYZED AZIDE ALKYNE CYCLOADDITION POLYMER NETWORKS by Abeer Ahmed Alzahrani M.S., Chemistry, King Abdul-Aziz University, 2005 B.S. Chemistry, University of Umm Al-Qura University, 2000 A thesis submitted to the Faculty of the Graduate School of the University of Colorado in partial fulfillment of the requirement for the degree of Doctor of Philosophy, Department of Department of Chemistry and Biochemistry, 2014 This thesis entitled: Copper-Catalyzed Azide Alkyne Cycloaddition Polymer Networks written by Abeer Ahmed Alzahrani has been approved for the Department of Chemistry and Biochemistry ___________________________ Christopher N. Bowman, PhD. Date____________ ___________________________ Jeffrey W. Stansbury, PhD. Date____________ Committee members: Christopher N. Bowman, Jeffrey W. Stansbury Devatha P Nair, Daniel L. Feldheim, and Wei Zhang The final copy of this thesis has been examined by The signatories, and we find that both the content and the form meet acceptable presentation standards of scholarly work in the above mentioned discipline. COPPER-CATALYZED AZIDE ALKYNE CYCLOADDITION POLYMER NETWORKS Alzahrani, Abeer Ahmed, Ph.D., Dept. of Department of Chemistry and Biochemistry Thesis directed by Patten Professor, Christopher N. Bowman Abstract The click reaction concept, introduced in 2001, has since spurred the rapid development and reexamination of efficient, high yield reactions which proceed rapidly under mild conditions. Prior to the discovery of facile copper catalysis in 2002, the thermally activated azide- alkyne or Huisgen cycloaddition reaction was largely ignored following its discovery in large part due to its slow kinetics, requirement for elevated temperature and limited selectivity. Now, arguably, the most prolific and capable of the click reactions, the copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction is extremely efficient and affords exquisite control of the reaction.
    [Show full text]
  • Phosphonamidate Peptide Synthesis by Staudinger Reactions of Silylated Phosphinic Acids Supporting Information
    Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2010 Phosphonamidate peptide synthesis by Staudinger reactions of silylated phosphinic acids and esters Ina Wilkening, Guiseppe del Signore and Christian P. R. Hackenberger Institute of Chemistry and Biochemistry Freie Universität Berlin Takustr. 3, 14195 Berlin Fax: +49-(0)30-838-52551 E-mail: [email protected] Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2010 Phosphonamidate peptide synthesis by Staudinger reactions of silylated phosphinic acids Supporting Information 1 GENERAL INFORMATION 3 2 SYNTHESIS OF ORGANIC COMPOUNDS 4 2.1 SYNTHESIS OF AZIDO COMPOUNDS 4 2.1.1 SYNTHESIS OF BENZYL AZIDE (9B) 4 2.1.2 SYNTHESIS OF PHENYLIC AZIDES 9A AND 9C-E 4 2.1.2.1 Phenyl azide (9a) 4 2.1.2.2 1-Azido-4-fluorobenzene (9c) 5 2.1.2.3 1-Azido-4-nitrobenzene (9d) 5 2.1.2.4 1-Azido-4-methoxybenzene (9e) 5 2.1.2.5 2-Azido-9H-fluorene (9g) 6 2.1.3 4-AZIDO BENZOIC ACID (9F) 6 2.2 SYNTHESIS OF PHOSPHINIC ESTERS 7 AND ACIDS 11 6 2.2.1 METHOD A: HEWITT REACTION 6 2.2.1.1 Methyl phenylphosphinate (7a) 7 2.2.1.2 Benzyl phenylphosphinate (7c) 7 2.2.1.3 Methyl octylphosphinate (7d) 8 2.2.2 SYNTHESIS OF 2-NITROBENZYL PHENYLPHOSPHINATE (7E) 8 2.2.3 SYNTHESIS OF OCTYL PHOSHINIC ACID (11B) 9 2.2.4 SYNTHESIS OF LEUCINE AND ALANIN PHOSPHINIC ACID DERIVATIVES 9 2.2.4.1 1-(Benzhydrylamino)-3-methylbutylphosphinic acid 9 2.2.4.2 1-amino-3-methylbutylphosphinic acid 10 2.2.4.3 1-(benzyloxycarbonylamino)-3-methylbutylphosphinic
    [Show full text]
  • The Synthesis and Characterisation of Halogen and Nitro Phenyl Azide
    Dissertation zur Erlangung des Dokorgrades der Fakultät für Chemie und Pharmazie der Ludwig-Maximilans-Universität München The synthesis and characterisation of halogen and nitro phenyl azide derivatives as highly energetic materials. von David Adam aus Glasgow , Schottland 2001 Index Acknowledgements 1 Abstract 3 1. Introduction 4 1.1 Azides 4 1.2 Nitro compounds 13 1.3 Nitrocarbons 16 1.4 Explosives 18 1.5 Theoretical Calculations 20 1.6 Pentazoles 23 2 Halogen substitued phenyl azides 27 2.1 2,4,6-tribromophenyl azide 27 2.2 2,4,6-trichlorophenyl azide 35 2.3 2,5,6-trichlorophenyl azide 42 2.4 2,4-dibromophenyl azide 43 2.5 2,4-dichlorophenyl azide 44 2.6 2,4,6-trifluorophenyl azide 44 2.7 2,3,4,5,6-pentafluorophenyl azide 47 2.8 2,6-diiodo-4-nitrophenyl azide 50 2.9 2,3,4,5,6-pentachlorophenyl azide 59 3. Nitro compounds 65 3.1 o-nitrophenyl azide 65 3.2 m-nitrophenyl azide 68 3.3 2,4-dinitrophenyl azide 70 3.4 2,4,6-trintrophenyl azide 72 3.5 1,3,5-triazido-2,4-dinitrobenzene 94 3.6 1,3,5-triazido-2,4,6-trinitrobenzene 100 3.7 hexakis (azidomethyl) benzene. 106 3.8 hexakis (methylnitrate) benzene 108 4. Decomposition and explosion experiments 111 4.1 Thermal decomposition of TNMA , DNTA and TNTA 111 4.2 Computational Aspects 118 4.3 Thermal decomposition of halogen substituted phenyl azides 121 4.4 Thermal decomposition of hexakis (azidomethyl) benzene 122 4.5 Drophammer Tests of TNMA, DNTA and TNTA 125 4.6 Calculation of the detonation velocity from molecular formula and structure for TNMA , DNTA and TNTA 133 4.7 Calculation of the detonation velocity from molecular formula and structure for a series of azido and nitro substituted benzenes 135 5 Calculation of compounds of the type C6 (NO2)6-n (N3)n 138 5.1 Structural discussion 144 5.2 Molecular structures 145 6.
    [Show full text]
  • Advancements in the Mechanistic Understanding of the Copper-Catalyzed Azide–Alkyne Cycloaddition
    Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition Regina Berg* and Bernd F. Straub* Review Open Access Address: Beilstein J. Org. Chem. 2013, 9, 2715–2750. Organisch-Chemisches Institut, Ruprecht-Karls-Universität doi:10.3762/bjoc.9.308 Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany Received: 09 August 2013 Email: Accepted: 30 October 2013 Regina Berg* - [email protected]; Bernd F. Straub* - Published: 02 December 2013 [email protected] Associate Editor: M. Rueping * Corresponding author © 2013 Berg and Straub; licensee Beilstein-Institut. Keywords: License and terms: see end of document. alkyne; azide; Click; copper; CuAAC; DFT study; Huisgen–Meldal–Sharpless cycloaddition; kinetics; reaction mechanism Abstract The copper-catalyzed azide–alkyne cycloaddition (CuAAC) is one of the most broadly applicable and easy-to-handle reactions in the arsenal of organic chemistry. However, the mechanistic understanding of this reaction has lagged behind the plethora of its applications for a long time. As reagent mixtures of copper salts and additives are commonly used in CuAAC reactions, the struc- ture of the catalytically active species itself has remained subject to speculation, which can be attributed to the multifaceted aggre- gation chemistry of copper(I) alkyne and acetylide complexes. Following an introductory section on common catalyst systems in CuAAC reactions, this review will highlight experimental and computational studies from early proposals to very recent and more sophisticated investigations, which deliver more detailed insights into the CuAAC’s catalytic cycle and the species involved. As diverging mechanistic views are presented in articles, books and online resources, we intend to present the research efforts in this field during the past decade and finally give an up-to-date picture of the currently accepted dinuclear mechanism of CuAAC.
    [Show full text]
  • Enthalpies of Vaporization of Organic and Organometallic Compounds, 1880–2002
    Enthalpies of Vaporization of Organic and Organometallic Compounds, 1880–2002 James S. Chickosa… Department of Chemistry, University of Missouri-St. Louis, St. Louis, Missouri 63121 William E. Acree, Jr.b… Department of Chemistry, University of North Texas, Denton, Texas 76203 ͑Received 17 June 2002; accepted 17 October 2002; published 21 April 2003͒ A compendium of vaporization enthalpies published within the period 1910–2002 is reported. A brief review of temperature adjustments of vaporization enthalpies from temperature of measurement to the standard reference temperature, 298.15 K, is included as are recently suggested reference materials. Vaporization enthalpies are included for organic, organo-metallic, and a few inorganic compounds. This compendium is the third in a series focusing on phase change enthalpies. Previous compendia focused on fusion and sublimation enthalpies. Sufficient data are presently available for many compounds that thermodynamic cycles can be constructed to evaluate the reliability of the measure- ments. A protocol for doing so is described. © 2003 American Institute of Physics. ͓DOI: 10.1063/1.1529214͔ Key words: compendium; enthalpies of condensation; evaporation; organic compounds; vaporization enthalpy. Contents inorganic compounds, 1880–2002. ............. 820 1. Introduction................................ 519 8. References to Tables 6 and 7.................. 853 2. Reference Materials for Vaporization Enthalpy Measurements.............................. 520 List of Figures 3. Heat Capacity Adjustments. ................. 520 1. A thermodynamic cycle for adjusting vaporization ϭ 4. Group Additivity Values for C (298.15 K) enthalpies to T 298.15 K.................... 521 pl 2. A hypothetical molecule illustrating the different Estimations................................ 521 hydrocarbon groups in estimating C ........... 523 5. A Thermochemical Cycle: Sublimation, p Vaporization, and Fusion Enthalpies...........
    [Show full text]