DOCSLIB.ORG

Synthesis and Reactions = R-Br in Our Course)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Synthesis and Reactions = R-Br in Our Course) Chem 201/Beauchamp Reactions and Mechanisms Worksheet 1 Starting organic compounds Br Br Br Br CH4 1o given 1o given o 1 given rearrangement example R-X Compounds (synthesis and reactions = R-Br in our course) 1. Make other R-Br compounds (nine examples for us, 3 primary examples given above and six more made below) a. R-Br from alkanes using free radical substitution (three part sequence: 1. Initiation 2. Propagation (2 steps) 3. termination 1. initiation - high energy photon ruptures the weakest bond (= halogen bond = homolytic cleavage) atoms bond energy Br-Br 46 3 Br h sp H3C-H 105 Br Br Br sp3 1o C-H 98 sp3 2o C-H 95 sp3 3o C-H 92 2a. propagation (step 1) - bromine atom abstracts H from weakest C-H bond and makes an H-Br bond sp3 C-Br 68 H-Br 88 H2 CH2 C Br H Br H3C H3C H 2b. propagation (step 2) - carbon free radical abstracts Br atom from bromine molecule and makes a C-Br bond CH Br H2 2 C H3C Br H3C Br Br 3. termination - two reactive free radicals find one another and combine H2 C CH CH2 H C 3 2 H C C H3C 3 CH3 H2 H2 C CH2 Br H C Br H3C 3 Other R-Br to make from our starting alkanes. Six possible RBr from our starting alkanes plus three primary RBr are given = 9 total. CH3 Br CH3 H CH3 H C Br 2 3 C C H C H C CH 3 H3C Br CH 3 H3C Br H C Br C Br 3 H2 Br h Br2 h Br 2 Br2 h Br 2 h 2 h Br2 h CH4 shown above There is no easy way to make a primary R-Br compound in our course yet (from our given starting structures). Three examples are provided above until we can do this. (Not in 201) y:\files\classes\201\201 Organic Reactions Worksheets.doc Chem 201/Beauchamp Reactions and Mechanisms Worksheet 2 In our course we will propose dibromoalkanes from ethane, propane and butane by using 2 equivalents of Br2/h. We will use these to make alkynes (ethyne, propyne and but-1-yne) Br Br Br Br Br CH C H3C C 1. 3 eqs. NaNR2 H C Br H C CH 1. 3 eqs. NaNR C CH3 3 2. workup 3 3 2 H 2. workup 2 1. 3 eqs. NaNR2 2 eqs. 2 eqs. 2. workup h h 2 eqs. Br2 Br h 2 Br2 b. Make R-Br from alcohols (reaction with HBr, SN2 at methyl and primary ROH, SN1 at secondary and tertiary ROH) SN2 reactions with with methyl and primary alcohols and H-Br (steps = 1. protonaton 2. SN2 reaction with bromide, with water leaving group) H2 Br H H2 C C H H Br H H H3C O H C O Br CH 3 2 O H C H 3 SN1 reactions with secondary and tertiary alcohols and H-Br (steps = 1. protonaton 2. water leaving group forms carbocation 3. bromide adds) CH3 CH3 H H H C H H Br H Br C H H3C O Br H3C O C C H3C CH3 H H3C CH3 SN1 reactions with rearrangement to more stable carbocation H H H H O H H O H2 H Br H H C C H2 O C C H2 H3C C CH3 C C H2 H2 H3C C CH3 C C H3C C CH3 H3C H H3C C CH3 H3C H H3C H (2S,3R) achiral (2S,3R) rearrangement CH3 (2S) to more stable carbocation Br add nucleophile (both sides) Later we will introduce a sequence to avoid H2 H2 C C rearrangements in situations like this. carbocation lose beta H+ + H3C C CH3 1. Ts-Cl / pyridine reactions (R ) (either side) 2. NaBr rearrange achiral H3C Br y:\files\classes\201\201 Organic Reactions Worksheets.doc Chem 201/Beauchamp Reactions and Mechanisms Worksheet 3 Examples of other R-Br to make from alcohols. There will be more possibilities as we progreas through organic chemistry. H 2 H2 H2 H2 H C C H H 3 C C H H3C C H 2 C O C H H3C C O CH O H2 H3C Br H2 H3C O CH3 SN2 S 2 SN2 SN2 N SN2 H H H 2 2 H2 H2 H2 C H H3C C H C C H H C C H H C O 3 3 H3C O C O H C C O CH O H 3 2 H2 shown above CH3 CH CH3 3 CH3 Br H3C CH H3C CH C H3C Br C Br H C Br H2 3 S 1 SN1 N SN1 SN1 CH CH3 3 CH3 O H3C H CH H H3C CH H C H C O H3C O H3C O H2 shown above c. Make R-Br from alkenes and H-Br (addition reactions – Markovnikov addition = form most stable carbocation) Addition reaction of H-Br to alkene - 1. form the most stable carbocation 2. add bromide (possible rearrangements) H Br H3C CH2 C C H Br Br CH H3C CH3 H C CH Make the most stable carbocation 3 3 H (rearrangements are possible) Alkene addition reactions with rearrangement to more stable carbocation. H H2 H H Br H2 H2 H2 C C C C H2 H2 C C C C H3C C CH2 H3C C CH3 H3C C CH3 H3C C CH3 H3C H CH Br H3C H 3 H3C Br (3R) rearrangement (3S) achiral achiral to more stable carbocation Other R-Br to make from alkenes Br CH CH3 3 CH3 H2 H C C 3 CH H3C CH C H3C Br C Br H3C Br H3C Br H2 HBr HBr HBr HBr HBr H H CH3 CH 2 C H3C C H2C C H3C CH2 C CH2 H2 shown above H3C CH2 y:\files\classes\201\201 Organic Reactions Worksheets.doc Chem 201/Beauchamp Reactions and Mechanisms Worksheet 4 d. Make RBr2 from alkanes + Br2/hυ (2x free radical substitution) or use Br2 + alkenes (addition reactions with Br2, forms bromonium bridge followed by anti attack of bromide at more + carbon). Addition reaction of Br-Br to alkene - 1. forms a bridging bromonium cation 2. adds bromide anti to bridge H Br H H CH2 C C Br Br Br C Br H CH2 H C anti attack at H H Br 2 bromonium bridge is more + carbon the most stable cation can be used to make alkynes Addition reaction of Br-Br to alkene - 1. forms a bridging bromonium cation 2. adds bromide anti to bridge H Br H H3C CH2 C C Br Br Br C Br H3C CH2 H C C anti attack at 3 H H more + carbon Br 2 bromonium bridge is the most stable cation can be used to make alkynes Addition reaction of Br-Br to alkene - 1. forms a bridging bromonium cation 2. adds bromide anti to bridge H H H2 Br C CH2 H C C Br Br 3 H C C Br H3C C Br 3 C CH2 H C C 2 anti attack at H2 H2 H more + carbon Br bromonium bridge is the most stable cation can be used to make alkynes Double E2 reaction to make alkynes: Use RBr2 + 3 equivalents NaNR2 Double elimination reaction (E2) forms alkynes using NaNR2 as the base. The acidity of sp C-H uses a third equivalent of the base and can form a terminal acetylide which is either protonated in a workup step or reacted further with an electrophile (2. methyl or primary RBr or 2. carbonyl compound or 2. epoxide) R H Na NH Na Na NH2 2 C Br R C H C further H2N H C C H C C reactions Br C R possible H H Br Na R H R = H, CH3 or CH3CH2 from our starting materials Na H H H H C O C Na H C C C H H C O C C H3C C R R H C 2. workup H C C H 3 H2 H2 C H2 C C Br C C CH3 H3C Br R C Na Na R 2. SN2 y:\files\classes\201\201 Organic Reactions Worksheets.doc Chem 201/Beauchamp Reactions and Mechanisms Worksheet 5 H H H H O H O H C O O C O C C H C CH3 H H C CH R H C 3 Na 3 C C 2. carbonyl R 3. workup addition Na R Na C H H H2 H C 2 O O C O C R C CH C CH O H2O Na C H H C 2. epoxide Na R CH R CH3 opening 3 3. workup Na Zipper reaction – moves internal alkynes to a terminal position, forming terminal acetylide The zipper reaction changes a linear internal alkyne into a terminal acetylide that can be made into a terminal alkyne (2. simple workup) or reacted with one of our three common electrophiles (2. methyl or primary RBr) or (2. aldehyde or ketone 3. workup) or (2. epoxide 3. workup). The steps of the zipper reaction are similar to the steps of tautomers in base: 1. proton off, 2. resonance, 3. proton on. This continues until the terminal alkyne is formed. Loss of the sp C-H forms the most stable anion and the reaction stops there until one of the workup possiblities completes the reaction. H H2 C CH C 2 CH2 C H N R C C C H3C H C C C C H3C H C R 3 H3C H N R H N R R N R R protonate H H R C o H C Me or 1 C C C H3C C RBr C C H3C H C C C aldehyde 3 H C C 3 C or ketone H2 H N R H2 H H epoxide R 2.
Load more

Recommended publications
  • The Reaction of Aminonitriles with Aminothiols: a Way to Thiol-Containing Peptides and Nitrogen Heterocycles in the Primitive Earth Ocean
    life Article The Reaction of Aminonitriles with Aminothiols: A Way to Thiol-Containing Peptides and Nitrogen Heterocycles in the Primitive Earth Ocean Ibrahim Shalayel , Seydou Coulibaly, Kieu Dung Ly, Anne Milet and Yannick Vallée * Univ. Grenoble Alpes, CNRS, Département de Chimie Moléculaire, Campus, F-38058 Grenoble, France; [email protected] (I.S.); [email protected] (S.C.); [email protected] (K.D.L.); [email protected] (A.M.) * Correspondence: [email protected] Received: 28 September 2018; Accepted: 18 October 2018; Published: 19 October 2018 Abstract: The Strecker reaction of aldehydes with ammonia and hydrogen cyanide first leads to α-aminonitriles, which are then hydrolyzed to α-amino acids. However, before reacting with water, these aminonitriles can be trapped by aminothiols, such as cysteine or homocysteine, to give 5- or 6-membered ring heterocycles, which in turn are hydrolyzed to dipeptides. We propose that this two-step process enabled the formation of thiol-containing dipeptides in the primitive ocean. These small peptides are able to promote the formation of other peptide bonds and of heterocyclic molecules. Theoretical calculations support our experimental results. They predict that α-aminonitriles should be more reactive than other nitriles, and that imidazoles should be formed from transiently formed amidinonitriles. Overall, this set of reactions delineates a possible early stage of the development of organic chemistry, hence of life, on Earth dominated by nitriles and thiol-rich peptides (TRP). Keywords: origin of life; prebiotic chemistry; thiol-rich peptides; cysteine; aminonitriles; imidazoles 1. Introduction In ribosomes, peptide bonds are formed by the reaction of the amine group of an amino acid with an ester function.
    [Show full text]
  • Recent Advances in Titanium Radical Redox Catalysis
    JOCSynopsis Cite This: J. Org. Chem. 2019, 84, 14369−14380 pubs.acs.org/joc Recent Advances in Titanium Radical Redox Catalysis Terry McCallum, Xiangyu Wu, and Song Lin* Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States ABSTRACT: New catalytic strategies that leverage single-electron redox events have provided chemists with useful tools for solving synthetic problems. In this context, Ti offers opportunities that are complementary to late transition metals for reaction discovery. Following foundational work on epoxide reductive functionalization, recent methodological advances have significantly expanded the repertoire of Ti radical chemistry. This Synopsis summarizes recent developments in the burgeoning area of Ti radical catalysis with a focus on innovative catalytic strategies such as radical redox-relay and dual catalysis. 1. INTRODUCTION a green chemistry perspective, the abundance and low toxicity of Ti make its complexes highly attractive as reagents and Radical-based chemistry has long been a cornerstone of 5 1 catalysts in organic synthesis. synthetic organic chemistry. The high reactivity of organic IV/III radicals has made possible myriad new reactions that cannot be A classic example of Ti -mediated reactivity is the reductive ring opening of epoxides. This process preferentially readily achieved using two-electron chemistry. However, the − high reactivity of organic radicals is a double-edged sword, as cleaves and functionalizes the more substituted C O bond, the selectivity of these fleeting intermediates can be difficult to providing complementary regioselectivity to Lewis acid control in the presence of multiple chemotypes. In addition, promoted epoxide reactions. The synthetic value of Ti redox catalysis has been highlighted by their many uses in total catalyst-controlled regio- and stereoselective reactions involv- 6−10 ing free-radical intermediates remain limited,2 and the synthesis (Scheme 1).
    [Show full text]
  • Hydrogen Atom Transfer-Mediated Cyclisations of Nitriles
    Hydrogen Atom Transfer-Mediated Cyclisations of Nitriles Oliver J. Turner,*[a,b] John A. Murphy,*[b] David. J. Hirst[a] and Eric P. A. Talbot*[a]† Abstract: Hydrogen atom transfer-mediated intramolecular C-C coupling reactions between alkenes and nitriles, using PhSiH3 and catalytic Fe(acac)3, are described. This introduces a new strategic bond disconnection for ring-closing reactions, forming ketones via imine intermediates. Of note is the scope of the reaction, including formation of sterically hindered ketones, spirocycles and fused cyclic systems. In the early 1960s, Kwiatek and Seyler first reported the use of metal hydrides as catalysts in the hydrogenation of α,β- unsaturated compounds.[1,2] The discovery by Halpern,[3] later elegantly developed by Norton,[4] that metal-hydride hydrogen atom transfer (HAT) proceeded by a free-radical mechanism opened the door to a wide range of alkene hydrofunctionalisation reactions. But it was the pioneering work by Mukaiyama[5] on the catalytic hydration of alkenes, using Co(acac)2 and oxygen, that sparked wider interest in the field of alkene hydrofunctionalisation. As a result, there now exists an extensive ‘toolkit’ for the addition of hydrogen and a functional group to an alkene with Markovnikov selectivity and high chemo-selectivity using cobalt, manganese and iron complexes.[6,7] Efforts have also been made to extend HAT methodologies to C-C bond formation, both in an intra- and intermolecular fashion: Baran’s group developed a general C-C coupling reaction, utilising electron-deficient alkenes as capable radical acceptors (Scheme 1ai).[8–10] Hydropyridylation of alkenes by intramolecular Minisci reaction was recently demonstrated by Starr,[11] which allows for the formation of structures such as Scheme 1.
    [Show full text]
  • Nitrile Synthesis with Aldoxime Dehydratases: a Biocatalytic Platform with Applications in Asymmetric Synthesis, Bulk Chemicals, and Biorefineries
    molecules Review Nitrile Synthesis with Aldoxime Dehydratases: A Biocatalytic Platform with Applications in Asymmetric Synthesis, Bulk Chemicals, and Biorefineries Pablo Domínguez de María Sustainable Momentum, SL, Av. Ansite 3, 4–6, 35011 Las Palmas de Gran Canaria, Canary Islands, Spain; [email protected]; Tel.: +34-6-0956-5237 Abstract: Nitriles comprise a broad group of chemicals that are currently being industrially produced and used in fine chemicals and pharmaceuticals, as well as in bulk applications, polymer chemistry, solvents, etc. Aldoxime dehydratases catalyze the cyanide-free synthesis of nitriles starting from aldoximes under mild conditions, holding potential to become sustainable alternatives for industrial processes. Different aldoxime dehydratases accept a broad range of aldoximes with impressive high substrate loadings of up to >1 Kg L−1 and can efficiently catalyze the reaction in aqueous media as well as in non-aqueous systems, such as organic solvents and solvent-free (neat substrates). This paper provides an overview of the recent developments in this field with emphasis on strategies that may be of relevance for industry and sustainability. When possible, potential links to biorefineries and to the use of biogenic raw materials are discussed. Keywords: biocatalysis; green chemistry; nitriles; aldoxime dehydratases; sustainability Citation: Domínguez de María, P. Nitrile Synthesis with Aldoxime Dehydratases: A Biocatalytic Platform with Applications in Asymmetric Synthesis, Bulk 1. Aldoxime Dehydratases as Biocatalysts for the Cyanide-Free Synthesis of Nitriles Chemicals, and Biorefineries. Nitriles comprise an important group of chemicals that are widely spread in industry Molecules 2021, 26, 4466. in a broad range of sectors, being used as products, solvents, polymers, commodities, or https://doi.org/10.3390/ as starting materials for the production of other chemicals such as amines, amides, etc.
    [Show full text]
  • Unusual Regioselectivity in the Opening of Epoxides by Carboxylic Acid Enediolates
    Molecules 2008, 13, 1303-1311 manuscripts; DOI: 10.3390/molecules13061303 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.org/molecules Communication Unusual Regioselectivity in the Opening of Epoxides by Carboxylic Acid Enediolates Luis R. Domingo, Salvador Gil, Margarita Parra* and José Segura Department of Organic Chemistry, Universitat de València, Dr. Moliner 50, 46100 Burjassot, Spain. Fax +34(9)63543831; E-mails: [email protected]; [email protected]; [email protected] * Author to whom correspondence should be addressed; E-mail: [email protected] Received: 29 May 2008; in revised form: 5 June 2008 / Accepted: 6 June 2008 / Published: 9 June 2008 Abstract: Addition of carboxylic acid dianions appears to be a potential alternative to the use of aluminium enolates for nucleophilic ring opening of epoxides. These conditions require the use of a sub-stoichiometric amount of amine (10% mol) for dianion generation and the previous activation of the epoxide with LiCl. Yields are good, with high regioselectivity, but the use of styrene oxide led, unexpectedly, to a mixture resulting from the attack on both the primary and secondary carbon atoms. Generally, a low diastereoselectivity is seen on attack at the primary center, however only one diastereoisomer was obtained from attack to the secondary carbon of the styrene oxide. Keywords: Lactones, lithium chloride, nucleophilic addition, regioselectivity, diastereoselectivity. Introduction Epoxides have been recognized among the most versatile compounds in organic synthesis, not only as final products [1] but as key intermediates for further manipulations. Accordingly, new synthetic developments are continuously being published [2]. Due to its high ring strain (around 27 Kcal/mol) its ring-opening, particularly with carbon-based nucleophiles, is a highly valuable synthetic strategy Molecules 2008, 13 1304 [3].
    [Show full text]
  • Highly Efficient Epoxidation of Olefins with Hydrogen Peroxide Oxidant Using Modified Silver Polyoxometalate Catalysts
    African Journal of Pure and Applied Chemistry Vol. 7(2), pp. 50-55, February 2013 Available online at http://www.academicjournals.org/AJPAC DOI: 10.5897/AJPAC12.060 ISSN 1996 - 0840 ©2013 Academic Journals Full Length Research Paper Highly efficient epoxidation of olefins with hydrogen peroxide oxidant using modified silver polyoxometalate catalysts Emmanuel Tebandeke 1*, Henry Ssekaalo 1 and Ola F. Wendt 2 1Department of Chemistry, Makerere University, P. O. Box 7062 Kampala, Uganda. 2Organic Chemistry, Department of Chemistry, Lund University, P. O. Box 124, 221 00 Lund, Sweden. Accepted 31 January, 2013 The catalytic epoxidation of olefins is an important reaction in chemical industry since epoxides are versatile and important intermediates in the synthesis of fine chemicals and pharmaceuticals. The current epoxidation procedures often use stoichiometric organic and sometimes toxic inorganic oxidants that are less favourable from an environmental and economical point of view. In contrast to such processes, catalytic epoxidation processes employing H2O2 oxidant are preferred for green processing. Herein is reported a highly efficient green process for the epoxidation of olefins using H2O2 oxidant and modified silver polyoxometalate catalysts at 65°C. The preparation and activity of the catalysts are described. The method enjoys >90% conversion and ≥99% selectivity to the epoxide for a variety of cyclic and linear olefins including terminal ones. The catalysts are easily recovered by filtration and are reusable several times. Key words: Epoxidation, olefins, hydrogen peroxide, polyoxometalate, silver catalysts. INTRODUCTION The catalytic epoxidation of olefins is very important in compared to organic peroxides and peracids (Jones, the chemical industry since epoxides are versatile and 1999; Lane and Burgess, 2003).
    [Show full text]
  • Reduction of Organic Functional Groups Using Hypophosphites Rim Mouselmani
    Reduction of Organic Functional Groups Using Hypophosphites Rim Mouselmani To cite this version: Rim Mouselmani. Reduction of Organic Functional Groups Using Hypophosphites. Other. Univer- sité de Lyon; École Doctorale des Sciences et de Technologie (Beyrouth), 2018. English. NNT : 2018LYSE1241. tel-02147583v2 HAL Id: tel-02147583 https://tel.archives-ouvertes.fr/tel-02147583v2 Submitted on 5 Jun 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THESE de DOCTORAT DE L’UNIVERSITE DE LYON EN COTUTELLE AVEC L'UNIVERSITÉ LIBANAISE opérée au sein de l’Université Claude Bernard Lyon 1 École Doctorale de Chimie-École Doctorale des Sciences et Technologies Discipline : Chimie Soutenue publiquement le 07/11/2018, par Rim MOUSELMANI Reduction of Organic Functional Groups Using Hypophosphites Devant le jury composé de Mme. Micheline DRAYE Université Savoie Mont Blanc Rapporteure M. Mohammad ELDAKDOUKI Université Arabe de Beyrouth Rapporteur Mme. Emmanuelle SCHULZ Université Paris 11 examinatrice M. Abderrahmane AMGOUNE Université Lyon 1 Président M. Mahmoud FARAJ Université Internationale Libanaise examinateur Mme. Estelle MÉTAY Université Lyon 1 Directrice de thèse M. Ali HACHEM Université Libanaise Directeur de thèse M. Marc LEMAIRE Université Lyon 1 Membre invité M.
    [Show full text]
  • Part I. the Total Synthesis Of
    AN ABSTRACT OF THE THESIS OF Lester Percy Joseph Burton forthe degree of Doctor of Philosophy in Chemistry presentedon March 20, 1981. Title: Part 1 - The Total Synthesis of (±)-Cinnamodialand Related Drimane Sesquiterpenes Part 2 - Photochemical Activation ofthe Carboxyl Group Via NAcy1-2-thionothiazolidines Abstract approved: Redacted for privacy DT. James D. White Part I A total synthesis of the insect antifeedant(±)-cinnamodial ( ) and of the related drimanesesquiterpenes (±)-isodrimenin (67) and (±)-fragrolide (72)are described from the diene diester 49. Hydro- boration of 49 provided the C-6oxygenation and the trans ring junction in the form of alcohol 61. To confirm the stereoselectivity of the hydroboration, 61 was convertedto both (t)-isodrimenin (67) and (±)-fragrolide (72) in 3 steps. A diisobutylaluminum hydride reduction of 61 followed by a pyridiniumchlorochromate oxidation and treatment with lead tetraacetate yielded the dihydrodiacetoxyfuran102. The base induced elimination of acetic acid preceded theepoxidation and provided 106 which contains the desired hydroxy dialdehydefunctionality of cinnamodial in a protected form. The epoxide 106 was opened with methanol to yield the acetal 112. Reduction, hydrolysis and acetylation of 112 yielded (t)- cinnamodial in 19% overall yield. Part II - Various N- acyl- 2- thionothiazolidineswere prepared and photo- lysed in the presence of ethanol to provide the corresponding ethyl esters. The photochemical activation of the carboxyl function via these derivatives appears, for practical purposes, to be restricted tocases where a-keto hydrogen abstraction and subsequent ketene formation is favored by acyl substitution. Part 1 The Total Synthesis of (±)-Cinnamodial and Related Drimane Sesquiterpenes. Part 2 Photochemical Activation of the Carboxyl Group via N-Acy1-2-thionothiazolidines.
    [Show full text]
  • Synthesis of Densely Substituted Pyridine Derivatives from Nitriles by a Non-Classical [4+2] Cycloaddition/1,5-Hydrogen Shift Strategy
    Synthesis of densely substituted pyridine derivatives from nitriles by a non-classical [4+2] cycloaddition/1,5-hydrogen shift strategy Wanqing Wu ( [email protected] ) South China University of Technology https://orcid.org/0000-0001-5151-7788 Dandan He South China University of Technology Kanghui Duan South China University of Technology Yang Zhou South China University of Technology Meng Li South China University of Technology Huanfeng Jiang South China University of Technology Article Keywords: pyridine derivatives, organic synthesis, medicinal chemistry. Posted Date: March 3rd, 2021 DOI: https://doi.org/10.21203/rs.3.rs-258126/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/18 Abstract A novel strategy has been established to assemble an array of densely substituted pyridine derivatives from nitriles and o-substituted aryl alkynes or 1-methyl-1,3-enynes via a non-classical [4 + 2] cycloaddition along with 1,5-hydrogen shift process. The well-balanced anities of two different alkali metal salts enable the C(sp3)-H bond activation as well as the excellent chemo- and regioselectivities. This protocol offers a new guide to construct pyridine frameworks from nitriles with sp3-carbon pronucleophiles, and shows potential applications in organic synthesis and medicinal chemistry. Introduction Compounds containing pyridine core structures, not only widely exist in natural products, pharmaceuticals, and functional materials,1–7 but also serve as useful and valuable building blocks for metal ligands.8,9 For instance, pyridine derivative Actos I10 is a famous drug for the treatment of type 2 diabetes; Bi-(or tri-)pyridines II11–15 are often used as ligands in metal-catalyzed reactions; Kv1.5 antagonist III16 and alkaloid papaverine IV17 are two representative isoquinolines as a promising atrial- selective agent and a smooth muscle relaxant, respectively (Fig.
    [Show full text]
  • Epoxidation of Olefins Using Molecular Oxygen
    Epoxidation of Olefins Using Molecular Oxygen Zhongxing Huang Sep 16th, 2015 1 Major Challenge in Catalysis Key points . Low temperature . Selective May 31st, 1993, C&EN News. 2 Most Ancient Chemistry-Oxygenase Monooxygenase catalyzes the incorporation of one atom of oxygen into the product Iron-Containing Enzymes, RSC Publishing, 2011. 3 Most Ancient Chemistry-Oxygenase Dioxygenase incorporates both oxygen atoms into the product Shen, B.; Gould, S. J. Biochemistry 1991, 30, 8936. Gould, S. J.; Kirchmeier, M. J.; LaFever, R. E. J. Am. Chem. Soc. 1996, 118, 7663. 4 Most Ancient Chemistry-Oxygenase Monooxygenase catalyzes the incorporation of one atom of oxygen into the product . Ideal system should avoid use of reductants Dioxygenase incorporates both oxygen atoms into the product 5 Most Ancient Chemistry-Oxygenase Monooxygenase catalyzes the incorporation of one atom of oxygen into the product . Ideal system should avoid use of reductants Dioxygenase incorporates both oxygen atoms into the product Ideal Dioxygenase incorporates both oxygen atoms into the epoxide 6 Most Ancient Chemistry-Oxygenase Monooxygenase catalyzes the incorporation of one atom of oxygen into the product . Ideal system should avoid use of reductants Dioxygenase incorporates both oxygen atoms into the product Ideal Dioxygenase incorporates both oxygen atoms into the epoxide 7 Industrial Process- EO and PO . Top chemicals produced in US (2004,103 ton) 1 sulfuric acid 35954 2 nitrogen 30543 3 ethylene 25682 4 oxygen 25568 5 propylene 15345 6 chlorine 12166 7 ethylene dichloride 12163 8 phosphoric acid 11463 9 ammonia 10762 10 sodium hydroxide 9508 11 benzene 7675 12 nitric acid 6703 13 ammonium nitrate 6021 14 ethylbenzene 5779 15 urea 5755 16 styrene 5394 17 hydrochloric acid 5012 18 ethylene oxide 3772 19 cumene 3736 20 ammonium sulfate 2643 8 Industrial Process- EO and PO .
    [Show full text]
  • Microflex Gloves Chemical Compatibility Chart
    1 1 1 2 2 3 1 CAUTION (LATEX): This product contains natural rubber 2 CAUTION (NITRILE: MEDICAL GRADE): Components used 3 CAUTION (NITRILE: NON-MEDICAL GRADE)): These latex (latex) which may cause allergic reactions. Safe use in making these gloves may cause allergic reactions in gloves are for non-medical use only. They may NOT be of this glove by or on latex sensitized individuals has not some users. Follow your institution’s policies for use. worn for barrier protection in medical or healthcare been established. applications. Please select other gloves for these applications. Components used in making these gloves may cause allergic reactions in some users. Follow your institution’s policies for use. For single use only. NeoPro® Chemicals NeoPro®EC Ethanol ■NBT Ethanolamine (99%) ■NBT Ether ■2 Ethidium bromide (1%) ■NBT Ethyl acetate ■1 Formaldehyde (37%) ■NBT Formamide ■NBT Gluteraldehyde (50%) ■NBT Test Method Description: The test method uses analytical Guanidine hydrochloride ■NBT equipment to determine the concentration of and the time at which (50% ■0 the challenge chemical permeates through the glove film. The Hydrochloric acid ) liquid challenge chemical is collected in a liquid miscible chemical Isopropanol ■NBT (collection media). Data is collected in three separate cells; each cell Methanol ■NBT is compared to a blank cell which uses the same collection media as both the challenge and Methyl ethyl ketone ■0 collection chemical. Methyl methacrylate (33%) ■0 Cautionary Information: These glove recommendations are offered as a guide and for reference Nitric acid (50%) ■NBT purposes only. The barrier properties of each glove type may be affected by differences in material Periodic acid (50%) ■NBT thickness, chemical concentration, temperature, and length of exposure to chemicals.
    [Show full text]
  • KIMBERLY-CLARK* Nitrile Glove Chemical Resistance Guide the Science of Protection
    KIMBERLY-CLARK* Nitrile Glove Chemical Resistance Guide The Science of Protection. Permeation Time Permeation Rate Color Code Chemical Name (minutes) (pg/cm2/min) Concentration Rating ASTM F739-99A ASTM F739-99A Acetaldehyde <1 353 99.5% Acetic Acid 5 482 99.7% Use the color code rating system below with the chart at right to determine the Acetone 1 466 99.5% Acetonitrile 1 329 99% chemical compatibility for incidental exposure. Acrylic Acid 1 57.8 99% Ammonium Hydroxide 7 395 30% Amyl Acetate 4 261 99% GREEN Analine 7 74.7 99.5% Benzaldehyde 78 0.57 99.5% The results for this specific chemical suggest that the glove A glove/chemical combination receives a GREEN Benzene <1 627 99.8% rating if: Benzyl Alcohol 5 86.8 99% would provide an adequate barrier for use in most applications. • The permeation breakthrough time is excellent n-Butanol 10 5.99 99.8% or good and the chemical has high volatility. Butyl Acetate 3 233 99% OR Carbon Disulfide 2 3.81 99% • The permeation breakthrough time is excellent Carbon Tetrachloride 5 48.9 99.5% Chloroform 1 958 99% and the chemical has low volatility. Citric Acid >480 Not Detected 50% Cyclohexane >480 Not Detected 99.7% Cyclohexanol 112 1.18 99% YELLOW Cyclohexanone 1 787 99.8% d-Limonene 107 0.157 97% The results require additional consideration to determine A glove/chemical combination receives a YELLOW n-Dibutyl Phthalate >480 Not Detected 99% rating if: 1,2-Dichlorobenzene <1 1179 99% suitability for use. • Any glove/chemical combination does not Dichloromethane 1 2006 99.9% meet either set of conditions required for Diesel Fuel, mixture 160 0.63 Mixture a GREEN or RED rating.
    [Show full text]