DOCSLIB.ORG

21.7 Hydrolysis of Carboxylic Acid Derivatives

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

21_BRCLoudon_pgs5-2.qxd 12/15/08 11:44 AM Page 1004 1004 CHAPTER 21 • THE CHEMISTRY OF CARBOXYLIC ACID DERIVATIVES substitution. Acyl substitution can be represented generally as follows, with E an elec- trophilic group and Y a nucleophilic group: = = O O S S R C X E Y R C Y E X (21.6) carboxylicL L acid+ L LanotherL + L derivative carboxylic acid derivative O an acyl group S R C X L L The term acyl substitution comes from the fact that substitution occurs at the carbonyl carbon of an acyl group. In other words, an acyl group is transferred in Eq. 21.6 between an X and a Y group. The group X might be the Cl of an acid chloride, the OR of an ester,L and soL on; this group is substitutedL by another groupL Y. This is precisely theL same type of reac- tion as esterification of carboxylic acids ( X L OH, E Y H OCH3; Sec. 20.8A). Acyl substitution reactions of carboxylic acidL derivatives= L areL the =majorL focus of this chapter. Although nitriles are not carbonyl compounds, the C'N bond behaves chemically much like a carbonyl group. For example, a typical reaction of nitriles is addition. Y RNC ' E Y RN"C A E (21.7) L 3+ L L 2 L (Compare this reaction with addition to the carbonyl group of an aldehyde or ketone.) Although the resulting addition products are stable in some cases, in most situations they react further. Like aldehydes and ketones, carboxylic acid derivatives undergo certain reactions involving the a-carbon. The a-carbon reactions of all carbonyl compounds are grouped together in Chapter 22. The reactivity of amides at nitrogen is discussed in Sec. 23.11D. 21.7 HYDROLYSIS OF CARBOXYLIC ACID DERIVATIVES All carboxylic acid derivatives have in common the fact that they undergo hydrolysis (a cleav- age reaction with water) to yield carboxylic acids. A. Hydrolysis of Esters Saponification of Esters One of the most important reactions of esters is the cleavage re- action with hydroxide ion to yield a carboxylate salt and an alcohol. The carboxylic acid itself is formed when a strong acid is subsequently added to the reaction mixture. O OCH3 O O_ Na| O OH C C C # % # % # % " " " 20% NaOH HCl OH (21.8) _ 5–10 min + %NO2 %NO2 %NO2 methyl 3-nitrobenzoateCH3OH 3-nitrobenzoic acid + (90–96% yield) 21_BRCLoudon_pgs5-2.qxd 12/15/08 11:44 AM Page 1005 21.7 HYDROLYSIS OF CARBOXYLIC ACID DERIVATIVES 1005 Ester hydrolysis in aqueous hydroxide is called saponification because it is used in the production of soaps from fats (Sec. 21.12B). Despite its association with fatty-acid esters, the term saponification can be used to refer to the hydrolysis in base of any carboxylic acid derivative. The mechanism of ester saponification involves the reaction of the nucleophilic hydroxide ion at the carbonyl carbon to give a tetrahedral addition intermediate from which an alkoxide ion is expelled. 1 1 1 1 O 1 O _ O S3 3 3 3 S3 3 R CO CH R" CO CH RCO H OCH (21.9a) 1 3 3 _ 3 LL1 LL1 LL1 + 3 1 OH "OH _ 1 3 1 tetrahedral3 addition intermediate The alkoxide ion, after expulsion as a leaving group (methoxide in Eq. 21.9a), reacts with the acid to give the carboxylate salt and the alcohol. 1 1 1 O O 1 S3 3 S3 3 RCO H _ OCH3 RCO _ H OCH3 (21.9b) LLL1 + 3 1 LL1 3 + L 1 pKa 4.5 pKa 15 = = The equilibrium in this reaction lies far to the right because the carboxylic acid is a much stronger acid than methanol. Le Chaˆtelier’s principle operates: The reaction in Eq. 21.9b removes the carboxylic acid from the equilibrium in Eq. 21.9a as its salt and thus drives the hydrolysis to completion. Hence, saponification is effectively irreversible. Although an excess of hydroxide ion is often used as a matter of convenience, many esters can be saponified with just one equivalent of _OH. Saponification can also be carried out in an alcohol solvent, even though an alcohol is one of the products of the reaction. If saponification were reversible, an alcohol could not be used as the solvent because the equilibrium would be driven toward start- ing materials. Acid-Catalyzed Ester Hydrolysis Because esterification of an acid with an alcohol is a reversible reaction (Sec. 20.8A), esters can be hydrolyzed to carboxylic acids in aqueous so- lutions of strong acids. In most cases, this reaction is slow and must be carried out with an ex- cess of water, in which most esters are insoluble. Saponification, followed by acidification, is a much more convenient method for hydrolysis of most esters because it is faster, it is irre- versible, and it can be carried out not only in water but also in a variety of solvents—even alcohols. As expected from the principle of microscopic reversibility (Sec. 4.9B), the mechanism of acid-catalyzed hydrolysis is the exact reverse of the mechanism of acid-catalyzed esterifica- tion (Sec. 20.8A). The ester is first protonated by the acid catalyst: 1 H OH| 2 1 L 1 H H H | 1 1 1 O 1 O O O % % % S3 3 S3 3 3 RCOCH3 R C OCH3 R "C OCH3 R "C A O|CH3 H2O LL1 LL1 LL| 1 L 1 + 1 (21.10a) 21_BRCLoudon_pgs5-2.qxd 12/15/08 11:44 AM Page 1006 1006 CHAPTER 21 • THE CHEMISTRY OF CARBOXYLIC ACID DERIVATIVES As in other acid-catalyzed reactions at the carbonyl group, protonation makes the carbonyl carbon more electrophilic by making the carbonyl oxygen a better acceptor of electrons. Water, acting as a nucleophile, reacts at the carbonyl carbon and then loses a proton to give the tetra- hedral addition intermediate: H O| OH OH S % 3 3 2 H2O 3 2 (21.10b) R C OCH3 R "C OCH3 2 3 R "C OCH3 H3O| LL LL LL + 2 OH2 | "OH "OH L 3 2 3 tetrahedral3 addition "H intermediate2 Protonation of the leaving oxygen converts it into a better leaving group. Loss of this group gives a protonated carboxylic acid, from which a proton is removed to give the carboxylic acid itself. OH OH H H OH| 2 R "C OCH3 L R "C" OCH3 L L H2O2 LL 2 | ""OH 2 2 OH 2 2 OH OH| OH OH 3 22S3 3 OH 3 2 ||2 R "COH R COH R "COHA 3 2 R "COA H3O LLL| 2 LLL2 LL2 L 2 + 2 2 CH3OH2 2 (21.10c) + 2 Let’s summarize the2 important differences between acid-catalyzed ester hydrolysis and ester saponification. First, in acid-catalyzed hydrolysis, the carbonyl carbon can react with the STUDY GUIDE LINK 21.3 relatively weak nucleophile water because the carbonyl oxygen is protonated. In base, the car- Mechanism of Ester Hydrolysis bonyl oxygen is not protonated; hence, a much stronger base than water—namely, hydroxide ion—is required to react at the carbonyl carbon. Second, acid catalyzes ester hydrolysis, but base is not a catalyst because it is consumed by the reaction in Eq. 21.9b. Finally, acid-cat- alyzed ester hydrolysis is reversible, but saponification is irreversible, again because of the Further Exploration 21.2 ionization in Eq. 21.9b. Cleavage of Tertiary Ester hydrolysis and saponification are both examples of acyl substitution (Sec. 21.6). Esters and Carbonless Carbon Paper Specifically, the mechanisms of these reactions are classified as nucleophilic acyl substitu- tion mechanisms. In a nucleophilic acyl substitution reaction, the substituting group reacts as a nucleophile at the carbonyl carbon. As in the reactions of aldehydes and ketones (Fig. 19.8, p. 909), nucleophiles approach the carbonyl carbon from above or below the plane of the car- bonyl group (Fig. 21.5), first interacting with the p* (antibonding) molecular orbital of the carbonyl group. As the result of this reaction, a tetrahedral addition intermediate is formed. The leaving group is expelled from this intermediate, departing from above or below the plane of the new carbonyl group. In saponification, the nucleophile is _OH, and in acid-catalyzed hydrolysis, the nucleophile is water; in both cases, the OR group of the ester is displaced. With the exception of the reactions of nitriles, most of Lthe reactions in the remainder of this chapter are nucleophilic acyl substitution reactions. They follow the same pattern as saponifi- cation, the only substantial difference being the identity of the nucleophiles and the leaving groups. 21_BRCLoudon_pgs5-2.qxd 12/15/08 11:44 AM Page 1007 21.7 HYDROLYSIS OF CARBOXYLIC ACID DERIVATIVES 1007 sp2-hybridized sp3-hybridized sp2-hybridized carbon carbon carbon ≈109Њ .. 1 .. ≈120Њ .. O.. R O.. ≈120Њ R´O C 1 Nuc Nuc _ Nuc 3 tetrahedral R´O addition intermediate Figure 21.5 The geometry of nucleophilic acyl substitution.The nucleophile (Nuc _) approaches the carbonyl 3 carbon above or below the carbonyl plane (gray) to form a tetrahedral intermediate.The leaving group (R O_) de- parts from above or below the plane of the newly formed carbonyl group (blue).The green arrows show the´ move- ment of the various groups. Hydrolysis and Formation of Lactones Because lactones are cyclic esters, they un- dergo the reactions of esters, including saponification. Saponification converts a lactone com- pletely into the carboxylate salt of the corresponding hydroxy acid. O O L L S L S C C O_ H2C O OH H2C L (21.11) _ L L + L H2C CH2 H2C CH2 OH L L L g-butyrolactone g-hydroxybutyrate Upon acidification, the hydroxy acid forms.
Recommended publications
  • The Reaction of Aminonitriles with Aminothiols: a Way to Thiol-Containing Peptides and Nitrogen Heterocycles in the Primitive Earth Ocean

    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.
  • Chemistry 0310 - Organic Chemistry 1 Chapter 6

    Chemistry 0310 - Organic Chemistry 1 Chapter 6

    Dr. Peter Wipf Chemistry 0310 - Organic Chemistry 1 Chapter 6. SN2 Reactions Nucleophilic substitution reactions occur when nucleophiles (electron-rich species) displace leaving groups on electrophiles (electron-poor species). The net result is the substitution of one group for another bonded to a carbon atom. Nucleophilicity is increased by a negative charge and an increase in the polarizability. The greater the size and the lower the electronegativity of an atom, the greater its polarizability. Leaving groups are stable species that can be detached with their bonding electrons from a molecule during reaction. Most good leaving groups are the conjugate bases of strong acids. Sulfonates (mesylates, tosylates, triflates, etc.) are popular leaving groups since they can be readily obtained from alcohols. Solvents also influence nucleophilicity. SN2 reactions are second-order reactions whose rates depend o the concentration of both the alkyl halide and the nucleophile. The transition state of the one-step SN2 process involves a trigonal bipyramidal carbon and results in an overall inversion of configuration. The order of reactivity of alkyl halides and alkyl sulfonates in SN2 reactions is CH3>1°>2°>3°. The activation energy, DG‡, determines the rate of a reaction: k = koexp(-DG‡/RT). The overall change in free energy, DG, determines the position of the thermodynamic equilibrium. A positive sign of DG is characteristic for an endergonic reaction, a negative DG is found for an exergonic process. The rate of a reaction can be measured and provides information about its mechanism. The reaction order is the sum of the exponents in the rate equation. Relative Leaving Group Abilities: Leaving Group Common Name krel AcO acetate 1 x 10-10 Cl chloride 0.0001 Br bromide 0.001 I iodide 0.01 O mesylate 1.00 H3C S O O O tosylate 0.70 H3C S O O O brosylate 2.62 Br S O O O nosylate 13 O2N S O O O fluorosulfate 29,000 F S O O O triflate 56,000 CF3 S O O O nonaflate 120,000 C4F9 S O O.
  • KINETICS of HYDROLYSIS of ACETIC ANHYDRIDE by IN-SITU FTIR SPECTROSCOPY an Experiment for the Undergraduate Laboratory

    KINETICS of HYDROLYSIS of ACETIC ANHYDRIDE by IN-SITU FTIR SPECTROSCOPY an Experiment for the Undergraduate Laboratory

    .tA... 5-4._l_a_b _o_r._a_t_o_r.:.y________ ) KINETICS OF HYDROLYSIS OF ACETIC ANHYDRIDE BY IN-SITU FTIR SPECTROSCOPY An Experiment for the Undergraduate Laboratory SHAKER HA.JI, CAN ERKEY University of Connecticut • Storrs, CT 06269-3222 he senior-level chemical engineering undergraduate laboratory course at the University of Connecticut con­ 2 T sists of two four-hour labs per week, during which groups of three to four students typically perform five ex­ Quite a few studies have been reported in the literature on the 2 periments during the course of the semester. Each experi­ kinetics of hydrolysis of acetic anhydride. [J, A,5l Eldridge and ment is studied for either one or two weeks, depending on its Piretl41 obtained the pseudo-first-order reaction rate constant complexity and the scale of the equipment. The students are using a batch reactor. To determine the acetic anhydride con­ given only the general goals for each experiment and are re­ centration, samples from the reactor were withdrawn into tared quired to define their own objectives, to develop an experi­ flasks containing 15-20 times the quantity of saturated aniline­ mental plan, to prepare a pre-lab report (including a discus­ water required to react with the sample. Since the anhydride sion of safety measures), to perform the experiments and ana­ rapidly acetylates the aniline, producing acetanilide and ace­ lyze the data, and to prepare group or individual written and/ tic acid, the samples were then titrated to determine the con­ or oral reports. centration of acetic acid. In another study, Shatyski and One or two of the experiments in this course involve reac­ Hanesianrsi determined the kinetics of the above reaction by tion kinetics.
  • Hydrogen Atom Transfer-Mediated Cyclisations of Nitriles

    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.
  • Nitrile Synthesis with Aldoxime Dehydratases: a Biocatalytic Platform with Applications in Asymmetric Synthesis, Bulk Chemicals, and Biorefineries

    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.
  • Recent Advances in the Direct Nucleophilic Substitution of Allylic

    Recent Advances in the Direct Nucleophilic Substitution of Allylic

    SHORT REVIEW ▌25 Recentshort review Advances in the Direct Nucleophilic Substitution of Allylic Alcohols through SN1-Type Reactions AlejandroSN1 Reactions of Allylic Alcohols Baeza,* Carmen Nájera* Departamento de Química Orgánica and Instituto de Síntesis Orgánica, University of Alicante, Apdo.99, 03080 Alicante, Spain Fax +34(965)903549; E-mail: [email protected]; E-mail: [email protected] Received: 03.10.2013; Accepted after revision: 06.11.2013 Abstract: Direct nucleophilic substitution reactions of allylic alco- hols are environmentally friendly, since they generate only water as a byproduct, allowing access to new allylic compounds. This reac- tion has, thus, attracted the interest of the chemical community and several strategies have been developed for its successful accom- plishment. This review gathers the latest advances in this methodol- ogy involving SN1-type reactions. 1 Introduction 2SN1-Type Direct Nucleophilic Substitution Reactions of Allylic Alcohols 2.1 Lewis Acids as Catalysts Alejandro Baeza was born in Alicante (Spain) in 1979. He studied 2.2 Brønsted Acids as Catalysts chemistry at the University of Alicante and he received his M.Sc. (2003) and Ph. D. degrees (2006) from here under the supervision of 2.3 Other Promoters Prof. José Miguel Sansano and Prof. Carmen Nájera. He was a post- 3 Conclusions and Outlook doctoral researcher in Prof. Pfaltz’s research group (2007–2010). In 2010 he returned to Alicante and joined the research group of Prof. Key words: S 1 reaction, allylic substitution, carbocations, allylic N Carmen Nájera. His main research interests focus on the development alcohols, green chemistry of new environmentally friendly methodologies, especially in asym- metric synthesis.
  • United States Patent Office Patented Nov

    United States Patent Office Patented Nov

    3,221,026 United States Patent Office Patented Nov. 30, 1965 2 3,221,026 prepared by reaction of a dicyanoketene acetal of the SALTS OF 1,1-DCYANO-2,2,2-TRIALKOXY formula ETHANES Owen W. Webster, Wilmington, Del, assignor to E. I. du Pont de Nemours and Company, Wilmington, Del., a corporation of Delaware No Drawing. Filed Feb. 13, 1962, Ser. No. 172,875 wherein R2 and R3 have the meanings defined above in the 2 Claims. (C. 260-340.9) general formula for the products of this invention, with This invention relates to salts of polycyano compounds, one molar equivalent of an alkali metal alkoxide of an and more particularly, to salts of polycyanopolyalkoxy alcohol having 1-8 carbon atoms at a temperature below ethanes and a process for their preparation. 10° C., and preferably at a temperature between 0 and The salts are derivatives of tetracyanoethylene which -80° C., in the presence of an inert reaction medium, is a very reactive compound that has received considerable e.g., an excess of the alcohol from which the alkoxide is study during the last few years. A large number of new 5 derived, or an ether such as diethyl ether, dioxane, tetra and valuable compounds have been prepared from it, and hydrofuran, ethylene glycol dimethyl ether and the like. now a new class of polycyano compounds is provided by As in the case of the reaction starting with tetracyano the present invention. ethylene, the reaction mixture in this case should also The novel compounds of this invention are salts of the be anhydrous to obtain the best results.
  • Leaving Group of Substrate Important

    Leaving Group of Substrate Important

    1 Recap... • Last two lectures we looked at substitution reactions • We found that there we two (extreme) mechanisms • SN1 H H H H H PhS R H R Br R SPh Br • And SN2 H H H H PhS + Br R Br PhS R • We looked at many of the factors that influenced which ..mechanism was operating... • Now we will turn our attention to elimination reactions 2 Elimination reactions NaOH NaOH or low Br H2O OH concentration • You have seen SN1 substitution • Reaction not sped up by altering nucleophile - it is not in RDS • In fact if we increase the amount / concentration of nucleophile we get the following... high O H + + + Br Br OH concentration H H • We observe an elimination reaction • Overall HBr is lost from the molecule • Isn't chemistry fun - these are the same conditions as substitution! • Next two lectures will look at the mechanisms for elimination • And how we control the nature of the reaction we observe... 3 Elimination, bimolecular E2 O H Br HO Br H H • E2 - Elimination bimolecular or 2nd order reaction • 2 molecules in the RDS or transition state H H H H H C H C H H C Br Br H O H C H O H C C H H H H C H C H H H • Two molecules in the rate determining step • So both the base and the substrate control the reaction • Both carbon skeleton & leaving group of substrate important In substitutions nucleophile acts as a nucleophile & attacks carbon In eliminations nucleophile acts as a base & attacks proton 4 Elimination, bimolecular E2: MO • Little confusing as need bonding & anti-bonding in same diagram! • Orbitals need to be parallel for maximum overlap
  • Citric Acid Cycle

    Citric Acid Cycle

    CHEM464 / Medh, J.D. The Citric Acid Cycle Citric Acid Cycle: Central Role in Catabolism • Stage II of catabolism involves the conversion of carbohydrates, fats and aminoacids into acetylCoA • In aerobic organisms, citric acid cycle makes up the final stage of catabolism when acetyl CoA is completely oxidized to CO2. • Also called Krebs cycle or tricarboxylic acid (TCA) cycle. • It is a central integrative pathway that harvests chemical energy from biological fuel in the form of electrons in NADH and FADH2 (oxidation is loss of electrons). • NADH and FADH2 transfer electrons via the electron transport chain to final electron acceptor, O2, to form H2O. Entry of Pyruvate into the TCA cycle • Pyruvate is formed in the cytosol as a product of glycolysis • For entry into the TCA cycle, it has to be converted to Acetyl CoA. • Oxidation of pyruvate to acetyl CoA is catalyzed by the pyruvate dehydrogenase complex in the mitochondria • Mitochondria consist of inner and outer membranes and the matrix • Enzymes of the PDH complex and the TCA cycle (except succinate dehydrogenase) are in the matrix • Pyruvate translocase is an antiporter present in the inner mitochondrial membrane that allows entry of a molecule of pyruvate in exchange for a hydroxide ion. 1 CHEM464 / Medh, J.D. The Citric Acid Cycle The Pyruvate Dehydrogenase (PDH) complex • The PDH complex consists of 3 enzymes. They are: pyruvate dehydrogenase (E1), Dihydrolipoyl transacetylase (E2) and dihydrolipoyl dehydrogenase (E3). • It has 5 cofactors: CoASH, NAD+, lipoamide, TPP and FAD. CoASH and NAD+ participate stoichiometrically in the reaction, the other 3 cofactors have catalytic functions.
  • Synthesis of Novel Single-Source Precursors for CVD of Mixed-Metal Tungsten Oxide

    Synthesis of Novel Single-Source Precursors for CVD of Mixed-Metal Tungsten Oxide

    Synthesis of novel single-source precursors for CVD of mixed-metal tungsten oxide Hamid Choujaa A thesis submitted for the degree of Doctor of Philosophy University of Bath Department of Chemistry March 2008 COPYRIGHT Attention is drawn to the fact that copyright of this thesis rests with its author. This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognize that its copyright rests with its author and that no quotation the thesis and no information derived from it may be published without the prior written consent of the author. This thesis may be made available for consultation within the University Library and may be photocopied or lent to other libraries for the purposes of consultation. TABLE OF CONTENTS Abstract ....................................................................................................................................... i Acknowledgements .................................................................................................................... iii Abbreviations and Acronyms .................................................................................................... iv 1. INTRODUCTION .................................................................................................................. 1 1.1 Generality about tungsten(VI) oxide ............................................................................. 1 1.1.1 The different lattice structures of tungsten oxide ........................................... 1 1.1.2 Electronic and
  • Carbonyl Chemistry I: Additions to Carbonyl Groups

    Carbonyl Chemistry I: Additions to Carbonyl Groups

    Paul Bracher Chem 30 – Section 4 Carbonyl Chemistry I: Additions to Carbonyl Groups Section Agenda 1) Lessons from Exam I, Course Feedbeck Mechanism on Web Site 2) Carbonyl Groups: Structure, Bonding, Molecular Orbitals, Geometry, Reactivity 3) Handout: In-Section Problem Set 4) Handout: In-Section Solution Set 5) Weekly Office Hours: Thursday, 3-4PM and 8-9PM, in Bauer Lobby Structure and Bonding · Carbonyl carbons are roughly sp2 hybridized Molecular Orbital Picture and planar with bond angles near 120 degrees bonding p orbital antibonding p* orbital · The C=O p bond is formed by the overlap of two unhybridized p orbitals. The bond is polarized due to the different electronegativities of carbon and oxygen. 105 o Resonance Model O O Bürgi-Dunitz angle · Another way to picture carbonyl groups is I II through an MO picture. Since the coefficient of · Resonance form II suggests that the carbon pO’s contribution is greater in pC=O, then atom is surrounded by less negative charge conservation of blending atomic orbitals into density than oxygen, rendering the carbon more molecular orbitals tells you that pC must be a electrophilic. larger contributor to the p*C=O orbital. · When reagents add to carbonyl double bonds, · The larger coefficient on oxygen in the filled the nucleophile attacks the carbon atom. orbital explains why the oxygen atom behaves as a Lewis base (it commonly complexes with · Due to the increased negative charge density Lewis acids). The larger coefficient on carbon on oxygen, Lewis acids (such as protons) in the empty antibonding orbital explains why it commonly complex with oxygen.
  • 8.6 Acidity of Alcohols and Thiols 355

    8.6 Acidity of Alcohols and Thiols 355

    08_BRCLoudon_pgs5-1.qxd 12/8/08 11:05 AM Page 355 8.6 ACIDITY OF ALCOHOLS AND THIOLS 355 ural barrier to the passage of ions. However, the hydrocarbon surface of nonactin allows it to enter readily into, and pass through, membranes. Because nonactin binds and thus transports ions, the ion balance crucial to proper cell function is upset, and the cell dies. Ion Channels Ion channels, or “ion gates,” provide passageways for ions into and out of cells. (Recall that ions are not soluble in membrane phospholipids.) The flow of ions is essen- tial for the transmission of nerve impulses and for other biological processes. A typical chan- nel is a large protein molecule imbedded in a cell membrane. Through various mechanisms, ion channels can be opened or closed to regulate the concentration of ions in the interior of the cell. Ions do not diffuse passively through an open channel; rather, an open channel contains regions that bind a specific ion. Such an ion is bound specifically within the channel at one side of the membrane and is somehow expelled from the channel on the other side. Remark- ably, the structures of the ion-binding regions of these channels have much in common with the structures of ionophores such as nonactin. The first X-ray crystal structure of a potassium- ion channel was determined in 1998 by a team of scientists at Rockefeller University led by Prof. Roderick MacKinnon (b. 1956), who shared the 2003 Nobel Prize in Chemistry for this work. The interior of the channel contains binding sites for two potassium ions; these sites are oxygen-rich, much like the interior of nonactin.