Addition of a Grignard Reagent to an Ester: Formation of a Tertiary Alcohol
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WO 2015/025175 Al 26 February 2015 (26.02.2015) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/025175 Al 26 February 2015 (26.02.2015) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C09K 5/06 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, PCT/GB2014/052580 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, 22 August 2014 (22.08.2014) KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (25) Filing Language: English OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (26) Publication Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (30) Priority Data: ZW. 13 15098.2 23 August 2013 (23.08.2013) GB (84) Designated States (unless otherwise indicated, for every (71) Applicant: SUNAMP LIMITED [GB/GB]; Unit 1, Satel kind of regional protection available): ARIPO (BW, GH, lite Place, Macmerry, Edinburgh EH33 1RY (GB). GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (72) Inventors: BISSELL, Andrew John; C/o SunAmp, Unit TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, 1, Satellite Place, Macmerry, Edinburgh EH33 1RY (GB). -
Copper(I) Complexes of P‐Stereogenic Josiphos and Related Ligands
Full Papers doi.org/10.1002/ejoc.202100146 Copper(I) Complexes of P-Stereogenic Josiphos and Related Ligands Ross A. Arthurs,[a] Alice C. Dean,[a] David L. Hughes,[a] and Christopher J. Richards*[a] Starting from (R)-Ugi’s amine, diastereoselective lithiation avoiding the isolation of air-sensitive phosphine intermediates. followed by Ar’PCl2 and then Ar’’MgBr led to the generation, as This protection methodology was also applied to the synthesis single diastereoisomers, of (R,Sp,Sphos) [Ar’=Ph, Ar’’=o-Tol] and of Josiphos/CuCl complexes derived from PCl3. In addition, (R,Sp,Rphos) [Ar’=o-Tol, Ar’’= Ph] PPFA ligand derivatives. Amine related bulky cobalt-sandwich complex-based derivatives were substitution of both with HPCy2 gave P-stereogenic Josiphos also obtained. Preliminary investigation revealed isolated CuCl ligands, and then addition of CuCl, the corresponding copper(I) complexes as competent catalyst precursors for enantioselec- complexes. The latter were also generated by using borane P tive conjugate addition reactions. and N protecting groups and in situ Cu(I) complexation, Introduction Although many ligands have been developed for application in asymmetric synthesis, relatively few have found widespread use. Of these so-called ‘privileged’ ligands,[1] one of the most successful class are the ferrocene-based Josiphos ligands A.[2] Numerous derivatives are known, obtained by varying the identity of R’ and R’’, and many are commercially available. This has aided the incorporation of A into many ligand screening exercises, often leading to a successful outcome.[3] In particular, in situ generated Josiphos-copper complexes have been applied Scheme 1. -
The Ozonolysis of Phenyl Grignard Reagent
University of Montana ScholarWorks at University of Montana Graduate Student Theses, Dissertations, & Professional Papers Graduate School 1971 The ozonolysis of phenyl Grignard reagent Gale Manning Sherrodd The University of Montana Follow this and additional works at: https://scholarworks.umt.edu/etd Let us know how access to this document benefits ou.y Recommended Citation Sherrodd, Gale Manning, "The ozonolysis of phenyl Grignard reagent" (1971). Graduate Student Theses, Dissertations, & Professional Papers. 8297. https://scholarworks.umt.edu/etd/8297 This Thesis is brought to you for free and open access by the Graduate School at ScholarWorks at University of Montana. It has been accepted for inclusion in Graduate Student Theses, Dissertations, & Professional Papers by an authorized administrator of ScholarWorks at University of Montana. For more information, please contact [email protected]. THE OZONOLYSIS OF PHENYL GRIGNARD REAGENT By Gale M. Sherrodd B.S., Rocky Mountain College, I969 Presented in partial fulfillment of the requirements for the degree of Master of Arts for Teachers UNIVERSITY OF MONTANA 1971 Approved by: Chairman, Board of Examiners De^ , Graduate *School / n ? / Date Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. UMI Number: EP39098 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. UMT DiMMtstion PuWiahing UMI EP39098 Published by ProQuest LLC (2013). Copyright in the Dissertation held by the Author. -
CF 7.4 V2.Indd
2007 VOLUME 7 NUMBER 4 Product Directory Grignard and Organozinc Reagents RIEKE® HIGHLY REACTIVE METALS GRIGNARD REAGENTS ORGANOZINC HALIDES DIALKYLMAGNESIUM AND DIALKYZINC REAGENTS 2-Pyridylzinc bromide: a shelf-stable 2-pyridyl anion equivalent; an important motif in many pharmacologically active molecules. sigma-aldrich.com 2 Table of Contents Sigma-Aldrich is committed to providing the most extensive portfolio of high-quality Grignard, organozinc, and other organometallic reagents, and we continually expand our product listing. Within each section of this directory, products are listed by increasing carbon content. Rieke® Highly Reactive Metals If viewing the electronic version simply select Grignard Reagents a category to jump to that section or activate Alkyl Alkenyl Alkynyl Aryl Heteroaryl your Adobe Bookmarks. You may also search by name, product number, molecular formula, Organozinc Halides or CAS registry number simply by using the “find” feature in Adobe (Ctrl+F in Windows or Alkyl Alkenyl Aryl Heteroaryl Introduction Command+F in a Mac environment). Dialkylmagnesium and Dialkylzinc Reagents If you are unable to find a reagent for your research “Please Bother Us” at [email protected], or contact your local Sigma-Aldrich office (see back cover). Foreword Reuben D. Rieke President and CEO, Rieke Metals, Inc. Professor Emeritus, University of Nebraska Lincoln, NE In the last 35 years, considerable research has been done in the area of generating reactive metals that can be used to synthesize novel organometallic reagents. In 1972, we reported a general approach for preparing highly reactive metal powders, relying on the reduction of metal salts with alkali metals in ethereal or hydrocarbon solvents. -
Grignard Reaction: Synthesis of Triphenylmethanol
*NOTE: Grignard reactions are very moisture sensitive, so all the glassware in the reaction (excluding the work-up) should be dried in an oven with a temperature of > 100oC overnight. The following items require oven drying. They should be placed in a 150mL beaker, all labeled with a permanent marker. 1. 5mL conical vial (AKA: Distillation receiver). 2. Magnetic spin vane. 3. Claisen head. 4. Three Pasteur pipettes. 5. Two 1-dram vials (Caps EXCLUDED). 6. One 2-dram vial (Caps EXCLUDED). 7. Glass stirring rod 8. Adaptor (19/22.14/20) Grignard Reaction: Synthesis of Triphenylmethanol Pre-Lab: In the “equations” section, besides the main equations, also: 1) draw the equation for the production of the byproduct, Biphenyl. 2) what other byproduct might occur in the reaction? Why? In the “observation” section, draw data tables in the corresponding places, each with 2 columns -- one for “prediction” (by answering the following questions) and one for actual drops or observation. 1) How many drops of bromobenzene should you add? 2) How many drops of ether will you add to flask 2? 3) 100 µL is approximately how many drops? 4) What are the four signs of a chemical reaction? (Think back to Chem. 110) 5) How do the signs of a chemical reaction apply to this lab? The Grignard reaction is a useful synthetic procedure for forming new carbon- carbon bonds. This organometallic chemical reaction involves alkyl- or aryl-magnesium halides, known as Grignard 1 reagents. Grignard reagents are formed via the action of an alkyl or aryl halide on magnesium metal. -
Experiment 12 Grignard Reaction; Preparation of Triphenylcarbinol
Experiment 12 Grignard Reaction; Preparation of Triphenylcarbinol In this experiment we will perform a Grignard addition to an ester. First we will form the Grignard reagent from magnesium and bromobenzene and then we will add it to methyl benzoate to produce triphenylcarbinol (also called triphenylmethanol). The overall sequence is shown in Figure 12.1 and the mechanism for the addition is shown in Figure 12.2. Figure 12.1 Grignard Addition to Methyl benzoate Br MgBr + Mg THF warm bromobenzene phenylmagnesium bromide O OMgBr OH C MgBr C C HCl OCH + MgBr(OH) 2 + 3 H2O methyl benzoate Triphenylcarbinol Since we are using an ester as our electrophile in this reaction, the nucleophilic Grignard reagent, prepared from the bromobenzene and magnesium, will add to the carbonyl two times to give the triphenyl adduct that on treatment with aqueous acid gives the free alcohol. Note that we have a ketone intermediate. This is even more reactive than the starting ester (why?) and reacts again with the Grignard reagent. Figure 12.2 Mechanism for Grignard Addition MgBr+ O O O OCH3 C C BrMg C OCH + -OCH 3 + 3 MgBr OH OMgBr HCl MgBr(OH) + C C H2O Physical Constants Compound Mol. Wt (g/mol) Density b.p. (°C) m.p. (°C) (g/mL) Bromobenzene 157.02 1.491 156 -31 Methyl benzoate 136.15 1.094 198-199 -12 Magnesium 24.31 1.740 - 648 Triphenylcarbinol 260.34 solid 360 160-163 Tetrahydrofuran (THF) 72.11 0.889 65-67 -108 Procedure: The set-up for this experiment is shown in Figure 12.3. -
University Microfilms, Inc., Ann Arbor, Michigan MONOMERIC ORGANOSILICON COMPOUNDS
This dissertation has been . micro&hned exactly as received 66-3860 CHAPMAN, Dwain R, 1929- MONOMERIC ORGANOSnJCON COMPOUNDS WITH POLYFUNCTIONAL GROUPS. Iowa State University of Science and Technology Ph.D., 1965 Chemistry, organic University Microfilms, Inc., Ann Arbor, Michigan MONOMERIC ORGANOSILICON COMPOUNDS . WITH POLYPUNCTIONAL GROUPS by Dwain R Chapman A Dissertation Submitted to the Graduate Faculty in Partial Fulfillment of The Requirements for the Degree of DOCTOR OF PHILOSOPHY Major Subject: Organic Chemistry Approved Signature was redacted for privacy. In Chai^ge of Major Work Signature was redacted for privacy. Head of Major Department Signature was redacted for privacy. Iowa State University Of Science and Technology Ames, Iowa 1965 11 TABLE OP CONTENTS' Page INTRODUCTION , 1 NOMENCLATURE 3• HISTORICAL 5 Cyclosilanes 5 Reactions of Cyclosilanes 6 Reactions of the Silicon-Silicon Bond 12 The Ultraviolet Absorption Properties 21 of Polysilanes Heterocyclic Polysilanes 23 . EXPERIMENTAL 28 Preparation of Cyclosilanes 30 Octaphenylcyclotetrasilane. 30 Decaphenylcyclopentasilane (Ila) 31 Dodecamethylcyclohexasilane 32 % Reactions of Octaphenylcyclotetrasilane 33 Octaphenylcyclotetrasilane with 33 , . phosphorus pentachloride In benzene 33 Tn xylene 33 Octaphenylcyclotetrasilane with 34 phosphorus trichloride (attempted). Octaphenylcyclotetrasilane with . 34 chlorine In carbon tetrachloride 34 In ether 34 In petroleum ether (b.p. 60-70 C) 36 In n-pentane 36 In ether containing hydroquinone ' 36 Ill Octaphenylcyclotetrasllane -
Nucl Ear Magnetic Resonance Spectroscopy. the Configurational Stability of Primary Grignard Reagents. Structure and Medium Effec
// lRepriatcd froo thc Jourad of tbc Aocrtc-' Chonicd Socicty, t?, {878 (1965).1 Nuclear MagneticResonance Spectroscopy. The ConfigurationalStability of Primary GrignardReagents. Structure and Medium Effects GeorgeM. Whitesidesand John D. Roberts IReprinted from the Journal of the American ChemicalSociety, 87,'1873 (196.j).I Copyright l9ti;i by the American Chemical Society and reprinted by permissionof the copyright owner NuclearMagnetic Resonance Spectroscopy. The ConfigurationalStability of Primary Gri-snard Reasents. Structureand Medium Effects' GeorgeM. Whitesidesand John D. Roberts Contribution lVo.3172 from the Gutes and Crellin Laboratories of Chemistry, Culifornia Instituteof Technology,Pasadena, CuliJ'orniu. ReceivedJanuarv 9, 1965 Qualitative and semiquontitative examination of the This observationsuggests that careful examination of lemperaturedependence of the RCH,:-Mg proton n.m.r. the spectrum oi this and related compounds in dif- spectra of several Grignard reagents indicates that the ferent solventsand at different concentrationsmight rate of inversiortat this center is relativel-v*insensitive to provide data pertinent to the mechanismof this in- the structurc of the group R. Secondar),Grignard re- version and to the nature o[ Grignard reagentsin ugentsinvert much more slowlv, if at all. The dependence solution. of the inversion rate of the primary orgonometallic Much of the modern work concernedwith the struc- compoundson solventcharacter and on added salts sug- ture of Grignard reagents has centered around at- gests that inversionproceeds br means of a mcchunism tempts to evaluate the importance of the so-called having kineric order greater than one. Schlenkequilibrium in describingthe Grignard reagent' In several well-known experiments, Dessy and co- workers examined the exchange reaction between Introduction labeledmagnesium bromide and diethyl-{and diphenyl- The precedingpaper2 presentedn.m.r. -
Schlenk Equilibrium in Toluene Solutions of Grignard Reagents
SCHLENK EQUILIBRIUM IN TOLUENE SOLUTIONS OF GRIGNARD REAGENTS Ants Tuulmets*, Marvi Mikk and Dmitri Panov Institute of Organic Chemistry, University of Tartu, Tartu, EE2400 Estonia Abstract Grignard reagents were prepared from η-butyl chloride, η-butyl bromide and bromobenzene in toluene in the presence of small amounts of diethyl ether. The reagents disproportionate according to the Schlenk equilibrium with the formation of a precipitate rich in magnesium halide. The supernatant solution comprises higly soluble complexes of the stoichiometry xR2Mg.yMgX2.zEt20 (x>y). The extent of side-reactions during the formation of these Grignard reagents increases in the order nBuCI<nBuBr<PhBr. Introduction Organomagnesium compounds can be prepared not only in conventional ethers but also in hydrocarbon media or without any solvent at all [1-5]. For many purposes the replacement of ethers by hydrocarbons of higher boiling point is expedient. The process in hydrocarbons is preferable, since the reaction medium is cheap, nonhygroscopic, and fire hazards are low. The use of unsolvated organomagnesium halides is limited to primary alkyl and aryl compounds. Branched chain primary, secondary, and tertiary alkyl halides, vinyl, allyl, and benzyl halides do not react under these conditions or produce Wurtz-type coupling products [2,6]. In the presence of one molar equivalent of complexing agents, e.g. ethers and tertiary amines, several organomagnesium compounds have been obtained in hydrocarbon media [5,7,8], Furthermore, alkylmagnesium bromide and chloride reagents in toluene containing less than one equivalent of diethyl ether have also been prepared [9-12]. Because the Grignard reagents in donor solvents are complexed at least with two solvent molecules per atom of magnesium, the reagents obtained in the presence of smaller amounts of donors should be considered as partially solvated. -
UNITED STATES PATENT OFFICE 2,677,686 PYRAZINEDERVATIVES and METHO) of PREPARING the SAME Victor K
Patented May 4, 1954 2,677,686 UNITED STATES PATENT OFFICE 2,677,686 PYRAZINEDERVATIVES AND METHO) OF PREPARING THE SAME Victor K. Smith, Jr., Feari River, and Samuel Kushner, Nanuet, N. Y., assignors to American Cyanamid Company, New York, N. Y., a corpo ration of Maine No Drawing. Application 5uly 22, 1952, Serial No. 300,336 8 Claims. (C. 260-250) 2 This invention relates to mono-substituted ous layer is extracted with a solvent, such as di pyrazine. More particularly, it relates to substi ethyl ether. The ether can be concentrated and tuted-2-carbonyl pyrazine. the desired compound crystallized out Or the The role of vitamins in nutrition is well known ether can be removed and the product distilled. i and assumes greater importance as new informa 5, The reaction of the present invention may be tion is made available concerning the particular carried out at a temperature of -10° to 15° C. function of each. Recently it has been found The reaction is complete in from about a few that folic acid was effective in curing macrocytic ininutes up to about tWO hours. anemias and other blood conditions. Also, Com The process of the present invention is de pounds which are folic acid antagonistS, Such as scribed in greater particularity by the following aninopterin, have been found useful in treating specific examples which are given by way of ill abnormal blood conditions such as leukemia. lustration and not limitation. it is well established that nicotinamide is an im Eacample 1 portant, vitamin of the B complex group and its deficiency is the specific cause of pelagira. -
Proceedings of the Indiana Academy of Science
The Solubility of Magnesium Bromide in Di-n-Butyl Ether John A. Ricketts and Paul Brown, DePauw University Rowley (1) has extensively investigated the solubility of magnesium bromide in diethyl ether, Et2 0, and has found that magnesium bromide forms a solid mono-, di-, and tri-etherate with transition temperatures of 12° C. (tri-etherate to di-etherate) and 22.6° C. (di-etherate to mono- etherate). This investigation measures the solubility of magnesium bro- 5° mide in di-n-butyl ether, Bu 2 0, in the temperature range of C. to 56° C. and also determines the chemical nature of the solid phase in equilibrium with the saturated solution of magnesium bromide in Bu 2 0. Experimental Solubility measurements were taken at approximately 5° C. inter- vals. Any of the fixed temperature points that were used were controlled to ± 0.02°C. Excess solid was added to 50 ml. of pure Bu 2 contained in a 100 ml. round-bottomed flask. All Bu 2 used in the experiments was purified by fractional distillation from sodium on to sodium and only the fraction which distilled in the temperature range 141-2° C. was used. The refractive index of the Bu>0 was measured as 1.3990 at 20° C. (lit. 1.3992). The vapor phase chromatogram of the liquid contained only a single peak. The flask was mounted in the constant temperature bath and the closed system stirred mechanically for a period of time ranging from 4 to 12 hours. Samples of the liquid phase were withdrawn, weighed, and analyzed, one sample for magnesium ion using EDTA with Erichrome Black T as indicator and another sample from the same flask for bromide ion by the Vohlhard method. -
Grignard Synthesis of Triphenylmethanol Reactions That Form Carbon-Carbon Bonds Are Among the Most Useful to the Synthetic Organic Chemist
1 Experiment 12: Grignard Synthesis of Triphenylmethanol Reactions that form carbon-carbon bonds are among the most useful to the synthetic organic chemist. In 1912, Victor Grignard received the Nobel prize in chemistry for his discovery of a new series of reactions that result in the formation of a carbon-carbon bond. A Grignard synthesis first involves the preparation of an organomagnesium reagent via the reaction of an alkyl bromide with magnesium metal: δ– δ+ R Br + Mg R MgBr The resulting “Grignard reagent” acts as both a good nucleophile and a strong base. Its nucleophilic character allows it to react with the electrophilic carbon in a carbonyl group, thus forming the carbon-carbon bond. Its basic property means that it will react with acidic compounds, such as carboxylic acids, phenols, thiols and even alcohols and water; therefore, reaction conditions must be free from acids and strictly anhydrous. Grignard reagents will also react with oxygen to form hydroperoxides, thus they are highly unstable when exposed to the atmosphere and are generally not isolated from solution. For a variety of reasons, anhydrous diethyl ether is the solvent of choice for carrying out a Grignard synthesis. Vapors from the highly volatile solvent help to prevent oxygen from reaching the reaction solution. In addition, evidence suggests that the ether molecules actually coordinate with and help stabilize the Grignard reagent: Et Et O R Mg Br O Et Et The magnesium metal used in the synthesis contains a layer of oxide on the surface that prevents it from reacting with the alkyl bromide. The pieces of metal must be gently scratched while in the ether solution to expose fresh surface area so that the reaction can commence.