DOCSLIB.ORG

Development of Methods for Regioselective Introduction of Difluoromethylene Unit Using Difluorocarbene

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Development of Methods for Regioselective Introduction of Difluoromethylene Unit Using Difluorocarbene Development of Methods for Regioselective Introduction of Difluoromethylene Unit Using Difluorocarbene Ryo Takayama February 2018 1 Development of Methods for Regioselective Introduction of Difluoromethylene Unit Using Difluorocarbene Ryo Takayama Doctoral Program in Chemistry Submitted to the Graduate School of Pure and Applied Sciences in Partial Fulfillment of the Requirements For the Degree of Doctor of Philosophy in Science at the University of Tsukuba 2 Contents Chapter 1. General Introduction Chapter 2. Introduction of Difluoromethylene Unit into Thiocarbonyl Compounds 2-1. S-Selective Difluoromethylation of Thiocarbonyl Compounds 2-1-1. Introduction 2-1-2. Synthesis of S-Difluoromethyl Thioimidates 2-1-3. Mechanistic Study 2-1-4. Comparison with the Reported Methods for the Generation of Difluorocarbene 2-1-5. Conclusion 2-2. Difluoromethylidenation of Dithioesters: Synthesis of Sulfur-Substituted Difluoroalkenes 2-2-1. Introduction 2-2-2. Synthesis of Sulfanylated Difluoroalkenes 2-2-3. Mechanistic Study 2-2-4. Comparison with the Reported Methods for the Generation of Difluorocarbene 2-2-5. Conclusion 2-3. Experimental Section 2-4. References 3 Chapter 3. Introduction of Difluoromethylene Unit into Dienol Silyl Ethers 3-1. Regioselective Difluorocyclopropanation of Dienol Silyl Ethers 3-1-1. Introduction 3-1-2. Regioselective Difluorocyclopropanation: Synthesis of Vinylated Difluorocyclopropanes 3-1-3. Conclusion 3-2. Metal-Free Synthesis of α,α-Difluorocyclopentanone Derivatives via Regioselective Difluorocyclopropanation/VCP Rearrangement of Dienol Silyl Ethers 3-2-1. Introduction 3-2-2. Metal-Free Synthesis of 5,5-Difluorocyclopent-1-en-1yl Silyl Ethers 3-2-3. Advantages of the Organocatalytic Synthesis 3-2-4. Conclusion 3-3. Synthesis of Fluorinated Cyclopentenones via Regioselective Difluorocyclopropanation of Dienol Silyl Ethers 3-3-1. Introduction 3-3-2. Preparation of 1-Fluorovinyl Vinyl Ketones 3-3-3. Fluorine-Directed and Fluorine-Activated Nazarov Cyclization: Regioselective Synthesis of α-Fluorocyclopentenones 3-3-4. Effect of Fluorine Substituent in Nazarov Cyclization 3-3-5. Conclusion 3-4. Experimental Section 3-5. References Chapter 4. Conclusions List of Publications Acknowledgement 4 Chapter 1. General Introduction 1-1. Biologically Useful Properties of Fluorine Compared with fluorine-free compounds, organofluorine compounds often exhibit unique behavior due to specific properties of fluorine substituents. For example, organofluorine compounds have weak intermolecular forces, generated by electronic polarization of molecules, because C–F bond is stable and electronic polarization is hardly to generate due to the strong electronegativity of fluorine. Because of this behavior, compounds with fluorine atoms have low boiling points. In addition, due to the strong electron-withdrawing property of fluorine, fluorine interacts with positive species such as a proton. Furthermore, being the second smallest substituent next to hydrogen, fluorine has been recognized as a mimic of hydrogen. Thus, organofluorine compounds are considered to be important in pharmaceutical, agrochemical, and functional material sciences. Among fluorinated compounds, difluoromethylene (-CF2-) or difluoromethylidene (=CF2) group containing compounds have attracted particular attention in the fields of pharmaceuticals and agrochemicals. For example, Flomoxef bearing a difluoromethylsulfanyl group exhibits antimicrobial activity (Figure 1).[1] Difluoroalkene 1 shows anticancer activity and dermatological activity, while difluorocyclohexanone 2 exhibits antimalarial activity.[2,3] Figure 1. Bioactive Compounds Bearing the Difluoromethylene or Difluoromethylidene Moiety 5 1-2. Synthetically Useful Properties of Fluorine From a synthetic point of view, there are several useful properties in fluorinated compounds. A fluorine substituent acts as an electron-withdrawing group because fluorine atom is most electronegative. When a fluorine atom is connected to a π-system, it can also act as an electron- donating group. This is because fluorine is on the same row as that of carbon in the periodical table, and thus donation of lone pairs of fluorine atom occurs efficiently. Because of this property, a fluorine substituent generally stabilizes an anion, whereas it destabilizes the anion at the α-position connected to a π-system. Likewise, it stabilizes the α-cation and destabilizes the β-cation (Figure 2). Figure 2. Properties of Fluorine Substituents. 1-3. Fluorine Installation Methods There are roughly two methods for the synthesis of difluoromethylene compounds. They are (i) direct introduction of fluorine substituents and (ii) introduction of building blocks containing fluorine substituents. As the background of this thesis, examples of these strategies are provided below. Although fluorine molecule (F2) or xenon difluoride (XeF2) had been used as electrophilic agent for direct fluorination, recently more stable, storable, and easily handled agents have been developed. For example, N-fluoropyridinium salt 3, chloromethyl-4-fluoro-1,4-diazoniumbicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor™), and N-fluorobenzenesulfonimide (NFSI) are widely used as electrophilic fluorinating agents (eq. 1–3, Scheme 1).[4–6] In these reactions, nucleophiles, such as 6 dienyl ester, enol, and vinyllithium, attack the electrophilic fluorine equivalents mentioned above. Scheme 1. Electrophilic Fluorine Introduction Apart from electrophilic fluorination, fluorination proceeds via nucleophilic attack of a fluoride ion to electrophilic substances. Pyridinium fluoride, potassium (alkali metal) fluoride, and N,N- diethylaminosulfur trifluoride (DAST) are often selected as the reagents (eq. 4–6, Scheme 2).[7–9] 7 Scheme 2. Nucleophilic Fluorine Introduction Although these direct nucleophilic and electrophilic fluorination methods are widely used, they suffer from drawbacks relating to the requirements of time-consuming processes (carbon-skeleton construction and fluorine installation) as well as the use of expensive fluorinating reagents. Introduction of a difluoromethylene unit using building blocks is useful, because diverse building blocks with a difluoromethylene unit have been developed until now. There are three kinds of one-carbon difluoromethylene sources: difluorocarbene, difluoromethyl cation (equivalent), difluoromethyl anion (equivalent), and difluoromethyl radical. Difluorocarbene, generated from chlorodifluoromethane and sodium hydroxide, reacts with indole to give 1-difluoromethylindole in 50% yield (eq. 7, Scheme 3).[10] On treatment with sulfonium salt 4, which acts as difluoromethyl cation equivalent, sodium p-toluenesulfonate provides difluoromethyl p-toluenesulfonate in 77% yield (eq. 8).[11] When benzaldehyde is treated with difluoromethyl phenyl sulfone, nucleophilic attack of difluoro(phenylsulfonyl)methide proceeds to give alcohol 5 in 65% yield (eq. 9).[12] 1- Pentene reacts with dibromodifluoromethane in the presence of a catalytic amount of copper(I) chloride to afford the radical addition product 6 in 57% yield (eq. 10).[13] 8 Scheme 3. Introduction of a Difluoromethylene Unit Using One-carbon Building Blocks There are several two- or more-carbon building blocks that allow to introduce a difluoromethylene or difluoromethylidene unit. For example, when benzaldehyde is treated with ethyl bromodifluoroacetate in the presence of zinc metal, the Reformatsky reaction proceeds, which allows installation of a carbonylated difluoromethylene unit (C2 unit introduction, eq. 11, Scheme 4).[14] Difluorovinylborane 7, generated from 2,2,2-trifluoroethyl tosylate, reacts with benzoyl chloride in the presence of a cupper salt to afford difluorovinylated ketone 8 in 78% yield (C2 unit introduction, [15] eq. 12). When 2-phenyl(trifluoromethyl)propene is treated with butyllithium, SN2’-type reaction proceeds to afford disubstituted difluoroalkene 9 in 93% yield (C3 unit introduction, eq. 13).[16] The difluorinated diene 11, prepared from trifluoromethyl ketone 10, reacts with benzaldehyde or 9 benzylideneaniline to produce the ring-fluorinated heterocycles 12 and 13 in 64% and 60% yields, respectively (C4 unit introduction, eq. 14 and 15).[17] Scheme 4. Introduction of Difluoromethylene Units Using Two- or More-carbon Building Blocks As shown above, the methods using fluorinated building blocks are of use because introduction of fluorine substituents and construction of carbon skeleton are carried out at the same time. I have focused on fluorinated one-carbon building blocks, especially the simplest difluorocarbene, which 10 can be applied to the synthesis of various difluoromethyl, difluoromethylene and difluoromethylidene compounds. Among one-carbon building blocks, difluorocarbene has particularly high and versatile reactivities. In spite of the merits, difluorocarbene has not been used widely, because the conditions for its generation are too severe to apply to a wide variety of compounds. Treatment of phenol with chlorodifluoromethane in the presence of excess amounts of sodium hydroxide afforded difluoromethoxybenzene in 65% yield (eq. 16, Scheme 5).[18] First, deprotonation of chlorodifluoromethane proceeds by sodium hydroxide. Then α-elimination of the generated chlorodifluoromethyl anion proceeds to form difluorocarbene. Finally, phenoxide, generated from phenol and sodium hydroxide, reacts with the generated difluorocarbene and protonation affords the difluoromethylated compound. This method requires the strong base. There is a reductive
Load more

Recommended publications
  • Selective Syntheses of Difluoromethylene Compounds Via Difluorocarbene Catalyses
    Selective Syntheses of Difluoromethylene Compounds via Difluorocarbene Catalyses 著者 青野 竜也 内容記述 この博士論文は全文公表に適さないやむを得ない事 由があり要約のみを公表していましたが、解消した ため、2017年10月2日に全文を公表しました。 year 2016 その他のタイトル ジフルオロカルベンを用いた触媒反応によるジフル オロメチレン化合物の選択的合成 学位授与大学 筑波大学 (University of Tsukuba) 学位授与年度 2015 報告番号 12102甲第7642号 URL http://hdl.handle.net/2241/00144162 Selective Syntheses of Difluoromethylene Compounds via Difluorocarbene Catalyses Tatsuya Aono February 2016 Selective Syntheses of Difluoromethylene Compounds via Difluorocarbene Catalyses Tatsuya Aono Doctoral Program in Chemistry Submitted to the Graduate School of Pure and Applied Sciences in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Science at the University of Tsukuba Contents Chapter 1 General Introduction 1 Chapter 2 O-Selective Difluoromethylation of Amides with Free Difluorocarbene 20 2.1. Introduction 21 2.2. Synthesis of Difluoromethyl Imidates 24 2.3. Mechanistic Considerations on O-Selective Difluoromethylation of Amides 31 2.4. Conclusion 33 2.5. Experimental Section 34 2.6. Reference 38 Chapter 3 Regioselective Syntheses of gem-Difluorocyclopentanone Derivatives with Transition Metal Difluorocarbene Complexes 39 3.1. Introduction 40 3.2. Domino Difluorocyclopropanation/Ring Expansion with Nickel Difluorocarbene Complex 45 3.3. [4 + 1] Cycloaddition with Copper Difluorocarbene Complex 58 3.4. Conclusion 66 3.5. Experimental Section 67 3.6. Reference 101 Chapter 4 Conclusion 104 List of Publications 105 Acknowledgement 106 Chapter 1 1. General Introduction Organofluorine compounds often exhibit unique properties and behaviors in comparison with nonfluorinated parent compounds, playing important roles as pharmaceuticals and agrochemicals. Because of the high bond dissociation energy of C–F bonds, organofluorine compounds are resistant to heat and chemicals, and stable to metabolism. In addition, organofluorine compounds have high lipophilicity.
    [Show full text]
  • Silylation and Characterization of of Piroxicam with Some Silylating Reagents
    Silylation and characterization of of piroxicam with some silylating reagents Mohammad Galehassadi ( [email protected] ) Azarbaijan Shahid Madani University Somayeh Jodeiri Azarbaijan Shahid Madani University Research Article Keywords: Piroxicam, Silyl ether, Organosilicon, Drug delivery, Lipophilic Posted Date: March 22nd, 2021 DOI: https://doi.org/10.21203/rs.3.rs-345479/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Silylation and characterization of of piroxicam with some silylating reagents Mohammad. galehassadi, *, a Somayeh Jodeiri a Department of Chemistry, Azarbaijan Shahid Madani University, Tabriz, Iran; e-mail: Email:[email protected] Tel: +984134327541 Mobile: +989144055400 Abstract: In this work, we synthesized some organosilicon derivatives of piroxicam. Due to the some properties of organosilicon compounds, including increased lipophilicity and thermal stabilization and prodrug for drugs, some silyl ethers of this drug were synthesized and characterized..Increasing of the lipophilic properties of this drug can be very important in the rate of absorption and its effectiveness. Graphic abstract: Keywords: Piroxicam, Silyl ether, Organosilicon, Drug delivery, Lipophilic 1.Introduction: Piroxicam is a painkiller and its main use is to reduce or stop pain. In osteoarthritis, this drug has anti-inflammatory effects. This drug is used to treat many diseases such as headache and toothache, leg pain and piroxicam reduces the production of prostaglandins by controlling cyclooxygenase, thus showing its effectiveness in reducing and eliminating pain. It is also used to relieve joint, bone and muscle pain. It is even used to control gout and menstrual cramps. It binds to a large amount of protein and is metabolized in the liver and then excreted in the urine.
    [Show full text]
  • Silyl Ketone Chemistry. Preparation and Reactions of Silyl Allenol Ethers. Diels-Alder Reactions of Siloxy Vinylallenes Leading to Sesquiterpenes2
    J. Am. Chem. SOC.1986, 108, 7791-7800 7791 pyrany1oxy)dodecanoic acid, 1.38 1 g (3.15 mmol) of GPC-CdCIz, 0.854 product mixture was then filtered and concentrated under reduced g (7.0 mmol) of 4-(dimethylamino)pyridine, and 1.648 g (8.0 mmol) of pressure. The residue was dissolved in 5 mL of solvent B and passed dicyclohexylcarbodiimide was suspended in 15 mL of dry dichloro- through a 1.2 X 1.5 cm AG MP-50 cation-exchange column in order to methane and stirred under nitrogen in the dark for 40 h. After removal remove 4-(dimethylamino)pyridine. The filtrate was concentrated under of solvent in vacuo, the residue was dissolved in 50 mL of CH30H/H20 reduced pressure, dissolved in a minimum volume of absolute ethanol, (95/5, v/v) and stirred in the presence of 8.0 g of AG MP-50 (23 OC, and then concentrated again. Chromatographic purification of the res- 2 h) to allow for complete deprotection of the hydroxyl groups (monitored idue on a silica gel column (0.9 X 6 cm), eluting first with solvent A and by thin-layer chromatography)." The resin was then removed by fil- then with solvent C (compound 1 elutes on silica as a single yellow band), tration and the solution concentrated under reduced pressure. The crude afforded, after drying [IO h, 22 OC (0.05 mm)], 0.055 g (90%) of 1 as product (2.75 g). obtained after drying [12 h, 23 OC (0.05 mm)], was a yellow solid: R 0.45 (solvent C); IR (KBr) ucz0 1732, uN(cH3)3 970, then subjected to chromatographic purification by using a 30-g (4 X 4 1050, 1090cm-'; I' H NMR (CDCI,) 6 1.25 (s 28 H, CH2), 1.40-2.05 (m, cm) silica gel column, eluting with solvents A and C, to yield 0.990 g 20 H, lipoic-CH,, CH2CH20,CH2CH,C02), 2.3 (t.
    [Show full text]
  • Activation of Silicon Bonds by Fluoride Ion in the Organic Synthesis in the New Millennium: a Review
    Activation of Silicon Bonds by Fluoride Ion in the Organic Synthesis in the New Millennium: A Review Edgars Abele Latvian Institute of Organic Synthesis, 21 Aizkraukles Street, Riga LV-1006, Latvia E-mail: [email protected] ABSTRACT Recent advances in the fluoride ion mediated reactions of Si-Η, Si-C, Si-O, Si-N, Si-P bonds containing silanes are described. Application of silicon bonds activation by fluoride ion in the syntheses of different types of organic compounds is discussed. A new mechanism, based on quantum chemical calculations, is presented. The literature data published from January 2001 to December 2004 are included in this review. CONTENTS Page 1. INTRODUCTION 45 2. HYDROSILANES 46 3. Si-C BOND 49 3.1. Vinyl and Allyl Silanes 49 3.2. Aryl Silanes 52 3.3. Subsituted Alkylsilanes 54 3.4. Fluoroalkyl Silanes 56 3.5. Other Silanes Containing Si-C Bond 58 4. Si-N BOND 58 5. Si-O BOND 60 6. Si-P BOND 66 7. CONCLUSIONS 66 8. REFERENCES 67 1. INTRODUCTION Reactions of organosilicon compounds catalyzed by nucleophiles have been under extensive study for more than twenty-five years. In this field two excellent reviews were published 11,21. Recently a monograph dedicated to hypervalent organosilicon compounds was also published /3/. There are also two reviews on 45 Vol. 28, No. 2, 2005 Activation of Silicon Bonds by Fluoride Ion in the Organic Synthesis in the New Millenium: A Review fluoride mediated reactions of fluorinated silanes /4/. Two recent reviews are dedicated to fluoride ion activation of silicon bonds in the presence of transition metal catalysts 151.
    [Show full text]
  • The Synthesis of N-Substituted Ferrocenes and C–H Activation
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Publikationsserver der RWTH Aachen University The Synthesis of N -Substituted Ferrocenes and C–H Activation Towards the Synthesis of Organosilanols Salih Oz¸cubuk¸cu¨ Dissertation The Synthesis of N -Substituted Ferrocenes and C–H Activation Towards the Synthesis of Organosilanols Von der Fakult¨at f¨ur Mathematik, Informatik und Naturwissenschaften der Rheinisch-Westf¨alischen Technischen Hochschule Aachen zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigte Dissertation vorgelegt von Master of Science Salih Oz¸cubuk¸cu¨ aus Gaziantep (T¨urkei) Berichter: Universit¨atsprofessor Dr. Carsten Bolm Universit¨atsprofessor Dr. Dieter Enders Tag der m¨undlichen Pr¨ufung: 22 Januar 2007 Diese Dissertation ist auf den Internetseiten der Hochschulbibliothek online verf¨ugbar. For everybody The work presented in this thesis was carried out at the Institute of Organic Chemistry of the RWTH-Aachen University, under the supervision of Prof. Dr. Carsten Bolm between January 2003 and July 2006. I would like to thank Prof. Dr. Carsten Bolm for giving me the opportunity to work on this exciting research topic, excellent conditions and support in his research group. I would like to thank Prof. Dr. Dieter Enders for his kind assumption of the co-reference. Parts of this work have already been published or submitted: ’Organosilanols as Catalysts in Asymmetric Aryl Transfer Reactions’ Oz¸cubuk¸cu,¨ S.; Schmidt, F.; Bolm, C. Org. Lett. 2005, 7, 1407. (This article has been highlighted in Synfact 2005, 0, 41.) ’A General and Efficient Synthesis of Nitrogen-Substituted Ferrocenes’ Oz¸cubuk¸cu,¨ S.; Scmitt, E.; Leifert, A.; Bolm, C.; Synthesis 2007, 389.
    [Show full text]
  • Copyrighted Material
    525 Index a alcohol racemization 356, 357 acetophenone 50–53, 293, 344, 348, 443 alkali metals 398 acetoxycyclization, of 1,6-enyne 76 alkaline earth metals 398 acetylacetone 48 N-alkenyl-substituted N,S-HC ligands 349 A3 coupling reactions 231, 232 3-alkyl-3-aryloxindoles 58 acrylonitriles 69, 211, 212, 310, 348 alkyl bis(trimethylsilyloxy) methyl silanes 122 activation period 123–125 – Tamao-Kumada oxidation of 122 active species 123 2-alkylpyrrolidyl-derived formamidinium acyclic alkane 62 precursors 516 acyclic aminocarbenes 499 alkyl silyl-fluorides 209 – ligands 503 alkyl-substituted esters 210 – metalation routes 500 N-alkyl substituted NHC class 119 acyclic aminocarbene species 499 alkynes acyclic carbene chemistry 500, 516–520 – boration of 225 acyclic carbene complexes – borocarboxylation 233, 234 – in Suzuki–Miyaura crosscoupling 505 – hydrocarboxylation 234, 235 acyclic carbene–metal complexes 505 – metal-catalyzed hydrosilylation of 132 acyclic carbenes – semihydrogenation 232, 233 – characteristic feature of 503 allenes 77 – donor abilities 502 – synthesis, mechanisms 203 – ligands 502 3-allyl-3-aryl oxindoles 60 –– decomposition routes 504 allylbenzene 345 –– donor ability 502, 503 – cross-metathesis (CM) reactions of –– metalation routes of 500 510 –– structural properties 503 allylic alkylations 509 – stabilized, by lateral enamines 518 allylic benzimidate acyclic carbone ligand 519 – aza-Claisen rearrangement of 514 – in gold-catalyzed rearrangements 520 allylic substitution 220 acyclic diaminocarbenes (ADCs) 4, 5, 499
    [Show full text]
  • IAEA TECDOC SERIES Production and Quality Control of Fluorine-18 Labelled Radiopharmaceuticals
    IAEA-TECDOC-1968 IAEA-TECDOC-1968 IAEA TECDOC SERIES Production and Quality Control of Fluorine-18 Labelled Radiopharmaceuticals IAEA-TECDOC-1968 Production and Quality Control of Fluorine-18 Labelled Radiopharmaceuticals International Atomic Energy Agency Vienna @ PRODUCTION AND QUALITY CONTROL OF FLUORINE-18 LABELLED RADIOPHARMACEUTICALS The following States are Members of the International Atomic Energy Agency: AFGHANISTAN GEORGIA OMAN ALBANIA GERMANY PAKISTAN ALGERIA GHANA PALAU ANGOLA GREECE PANAMA ANTIGUA AND BARBUDA GRENADA PAPUA NEW GUINEA ARGENTINA GUATEMALA PARAGUAY ARMENIA GUYANA PERU AUSTRALIA HAITI PHILIPPINES AUSTRIA HOLY SEE POLAND AZERBAIJAN HONDURAS PORTUGAL BAHAMAS HUNGARY QATAR BAHRAIN ICELAND REPUBLIC OF MOLDOVA BANGLADESH INDIA ROMANIA BARBADOS INDONESIA RUSSIAN FEDERATION BELARUS IRAN, ISLAMIC REPUBLIC OF RWANDA BELGIUM IRAQ SAINT LUCIA BELIZE IRELAND SAINT VINCENT AND BENIN ISRAEL THE GRENADINES BOLIVIA, PLURINATIONAL ITALY SAMOA STATE OF JAMAICA SAN MARINO BOSNIA AND HERZEGOVINA JAPAN SAUDI ARABIA BOTSWANA JORDAN SENEGAL BRAZIL KAZAKHSTAN SERBIA BRUNEI DARUSSALAM KENYA SEYCHELLES BULGARIA KOREA, REPUBLIC OF SIERRA LEONE BURKINA FASO KUWAIT SINGAPORE BURUNDI KYRGYZSTAN SLOVAKIA CAMBODIA LAO PEOPLE’S DEMOCRATIC SLOVENIA CAMEROON REPUBLIC SOUTH AFRICA CANADA LATVIA SPAIN CENTRAL AFRICAN LEBANON SRI LANKA REPUBLIC LESOTHO SUDAN CHAD LIBERIA SWEDEN CHILE LIBYA CHINA LIECHTENSTEIN SWITZERLAND COLOMBIA LITHUANIA SYRIAN ARAB REPUBLIC COMOROS LUXEMBOURG TAJIKISTAN CONGO MADAGASCAR THAILAND COSTA RICA MALAWI TOGO CÔTE D’IVOIRE
    [Show full text]
  • US2979539.Pdf
    2,979,539 United States Patent Office Patented Apr. 11, 1961 2 fluoride, vinylidene chloride, vinyl chloride, 1,1-difluoro dichloroethylene, propene, ethylene, 3,3,4,4,4-pentafluoro 2,979,539 buetene-1, perfluoropropene, and hexafluorobutene-1. DFLUOROCAR BENE FREE RADCALS IN THE Generally the ethylenes are preferred, particularly the SYNTHESS OF FLUORNATED OLEFNC COM fluorinated ethylenes. The use of tetrafluoroethylene in POUNDS this process, producing perfluoropropene, constitutes a Louis A. Errede, St. Paul, and Wesley R. Peterson, North particularly preferred embodiment. It may also be desir Oaks, Minn, assignors to Minnesota Mining and Man able to use other perhalogenated ethylenes, such as tri ufacturing Company, St. Paul, Minn., a corporation of fluorochloroethylene, as a reactant. Delaware - 0 Any method can be employed to produce the difluoro carbene radical, providing the free radical is available Filed Jan. 6, 1959, Ser, No. 785,246 for the addition reaction. Such methods include the 7 Claims. (CI. 260-653.3) production of difluorocarbene during the pyrolysis of CHCIF, as described in U.S. 2,551,573. It is also pos - This invention relates to a process for the manufacture 15 sible to obtain the difluorocarbene free radical during of unsaturated fluorine-containing compounds. In one the pyrolysis of tetrafluoroethylene at temperatures above aspect, this invention relates to the addition of a difluoro 750° C. However, for the purposes of this invention, carbene radical to an ethylenically unsaturated compound the method of producing difluorocarbene is not critical. to produce higher molecular weight fluorine-containing Because of the relatively short life of the difluoro compounds.
    [Show full text]
  • Preparation of Perfluorinated Ionomers
    PREPARATION OF PERFLUORINATED IONOMERS FOR FUEL CELL APPLICATIONS by TODD STEPHEN SAYLER JOSEPH S. THRASHER, COMMITTEE CHAIR RICHARD E. FERNANDEZ, Ph.D. ANTHONY J. ARDUENGO, Ph.D. MARTIN G. BAKKER, Ph.D. KEVIN H. SHAUGHNESSY, Ph.D. DARRYL D. DESMARTEAU, Ph.D. A DISSERTATION Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Chemistry in the Graduate School of The University of Alabama TUSCALOOSA, ALABAMA 2012 Copyright Todd Stephen Sayler 2012 ALL RIGHTS RESERVED ABSTRACT One of the major issues with the current membrane technology for polymer electrolyte membrane fuel cells is the low conductivity seen at low relative humidity. This dissertation discloses the preparation of perfluorinated polymers with higher densities of acid sites and higher conductivities to overcome this issue. These materials are prepared using a system designed to safely synthesize and polymerize tetrafluoroethylene (TFE) on a hundred gram scale. The copolymerization of TFE and perfluoro-2-(2-fluorosulfonylethoxy) propyl vinyl ether (PSEPVE) to prepare materials with varying ratios of the two monomers was carried out by solution, bulk, and emulsion polymerization techniques. Additionally, the homopolymer of PSEPVE has been prepared and characterized by MALDI-TOF mass spectrometry, which shows the low molecular weight distribution seen in other similar materials in the literature is due to a high rate of β-scission termination. Spectroscopic measurements and thermal analysis were carried out on these samples to obtain better characterization than was currently available. Producing polymers with a higher amount of PSEPVE, and thus higher density of acid sites, leads to the materials becoming water soluble after hydrolysis.
    [Show full text]
  • Cycloaddition Reactions of Ni(0) Difluorocarbene Complexes: Investigating the Formation of Various Perfluorometallacycles
    Cycloaddition Reactions of Ni(0) Difluorocarbene Complexes: Investigating the Formation of Various Perfluorometallacycles Alexandra Rochon Thesis submitted in partial fulfillment of the requirements for the Master’s degree in Chemistry Department of Chemistry and Biomolecular Sciences Faculty of Science University of Ottawa © Alexandra Rochon, Ottawa, Canada, 2019 Abstract Formation of carbon–fluorine and carbon–fluoroalkyl bonds via transition metal complexes represents an efficient synthetic route towards a wide array of valuable fluorinated organic compounds and fluorinated metallacycles offer a potentially green and atom economical pathway towards these functionalized fluorocarbons. This thesis is focused on cycloaddition reactions of Ni=CF2 complexes with fluoroalkenes (FAs) and acetylenes. Cycloaddition reactions of the FAs vinylidene fluoride (CF2=CH2) and perfluoro(methyl vinyl ether) [CF2=CF(OCF3)] with the electron-rich Ni(0) fluorocarbene, Ni=CF2[P(OMe)3](dppe) affords stable metallacyclobutane complexes, likely through a 1,4-diradical mechanism previously investigated for analogous reactions using computational chemistry. With CF2=CHF (TrFE), however, the observed products are the C3 alkene E-CHF=CF(CF3) and the metallacyclopentane complex, Ni(C4H2F6)(dppe), derived from oxidative coupling of two additional equivalents of TrFE. It is proposed that the instability of the initially formed metallacyclobutane gives rise to a 2,1-F shift, yielding the C3 alkene complex. Reaction of the latter with excess TrFE then liberates the C3 alkene, forming the TrFE alkene complex followed by the observed metallacyclopentane product. In the reaction of 1a with chlorotrifluoroethylene (CF2=CFCl) a single regioisomer of the metallacyclobutane is observed, but reacts further in THF solvent via α-Cl migration to Ni, affording the tetrafluoroallyl complex, NiCl(CF2CF=CFH), in which one F has been replaced by a hydrogen.
    [Show full text]
  • Transcription 12.02.10A
    Lecture 10A • 02/10/12 Protecting groups I want to show you another common protecting group used for alcohols. It’s the formation of what are known as silyl ethers. The version that your text has is the TMS ether. Don’t get that confused with tetramethylsilane, which is our standard that we use in NMR; this is trimethylsilyl; this is very close in form. What it is – trimethylsilyl chloride is the reagent that’s generally used. When you react it with an alcohol, the silicon-chlorine bond is active enough that you’re able to do an Sn2-style reaction, even is you just have the neutral alcohol. You might notice that there’s a whole bunch of alkyl groups on the silicon; how can you do an Sn2 with something that’s got that much steric hinderance? Silicon’s larger enough that you don’t have the same form of steric crowding, so this reaction is able to take place. We have the regular form of deprotonation step afterwards. If it weren’t for the fact that we have a silicon there instead of a carbon, this would just be a regular old ether, but that’s why this is called a silyl ether. That somes from the fact that SiH4 is called silane. The -ane is actually used for other atoms besides carbon. You can have phosphane, silane – usually means add hydrogens to that particular element. Silicon can take four just like carbon because it’s in the same column of the periodic table as carbon. This particular protecting group is very widely used, but it has certain drawbacks, in that it very easily reacts in both acidic and basic media.
    [Show full text]
  • 1 Difluoromethylation and Difluoroalkylation of (Hetero) Arenes
    3 1 Difluoromethylation and Difluoroalkylation of (Hetero) Arenes: Access to Ar(Het)–CF2H and Ar(Het)–CF2R Yu‐Lan Xiao and Xingang Zhang Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai Institute of Organic Chemistry, Center for Excellence in Molecular Synthesis, CAS Key Laboratory of Organofluorine Chemistry, 345 Lingling Road, Shanghai 200032, China 1.1 ­Introduction The difluoromethylation of arenes has been given increasing attention due to the unique properties of the difluoromethyl group (CF2H), which is considered as a bioisostere of hydroxyl and thiol groups and also as a lipophilic hydrogen bond donor [1]. Thus, the incorporation of CF2H into an aromatic ring has become an important strategy in medicinal chemistry [2]. Conventional method for the syn- thesis of difluoromethylated arenes relies on the deoxyfluorination of aromatic aldehydes with diethylaminosulfur trifluoride (DAST) [3]. However, this method has a modest functional group tolerance and high cost. Transition‐metal‐cata- lyzed cross‐coupling difluoromethylation is one of the most efficient strategies to access this class of compounds. Over the past few years, impressive achieve- ments have been made in this field [4]. In this chapter, we describe three modes of difluoromethylation of aromatics: nucleophilic difluoromethylation, catalytic metal difluorocarbene‐involved coupling reaction (MeDIC), and radical difluoromethylation. 1.2 ­Difluoromethylation of (Hetero)aromatics 1.2.1 Transition‐Metal‐Mediated/Catalyzed Nucleophilic Difluoromethylation of (Hetero)aromatics Copper is the first transition metal that has been used for mediating nucleophilic difluoromethylation of (hetero)aromatics. In 1990, Burton et al. synthesized the first difluoromethyl copper complex by metathesis reaction between [Cd(CF2H)2] and CuBr [5].
    [Show full text]