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14.8 Ester Hydrolysis 14,7 Thioesters

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445 CHAPTERl4 Acidsand TheirDerivatives 14,7Thioesters AIM: To write on equotion for the formotion of o thioester. The carboxylic esters we have seen so far are oxyestersbecause their car- Focus boxyl groups contain two oxygen atoms. In thioesters, the oxygen in the Thioesters are biologically C-O-C link of an oxyesteris replacedby sulfur: important. .o o / / R-C or RCOOR R-C or RCOSR \ -R S-R Oxyester Thioester Thioesters can be prepared in the same way as oxyesters.A thiol is used instead of an alcohol: o / R-C + RS-H .+ R-c/ + H-oH t* OH Carboxylicacid Thiol Thioester Water If an acid anhydride is used in the esterification of a thiol, the process is an acylation: rAcvl qroup //o (-" R-C \ro .roH \ + RS-H + R-C + R-C t* *-to \ 'o Acidanhydride Thiol Thioester Carboxylic acid Certain thioesters have biological significance. They transfer acyl groups during the qmthesis and degradation of such substancesas carbo- hydrates, amino acids, and fatty acids. Acetyl coenzyme A is the most important acyl transfer agent in lMng organisms. This compound is the thioester of acetic acid and a thiol, coenz\rmeA: o o / // CH3-C. + HSCoA +CH3-C + HrO \ t OH aoo Acetic acid CoenzyrneA Aceryl coenzymeA Water 14.8 Esterhydrolysis AIM: To write an equotionfor the acid' or bose-catolyzed hydrolysisof on ester. Estersmay be hydrolyzed to their component acids and If an ester is heated with water for severalhours, usually very little happens. alcohols. In strong acid solutions, however, ester hydrolysis is rapid becauseit is cat- I4.8 EsterHydrolysis 447 alyzed by hydro gen ions : o o tl H- tl cH3-c-ocH2cH3 + H-OH cH3-c-OH + HOCH2CHS Ethyl acetate Aceticacid Ethanol Sincethis hydrolysis processis reversible,a large excessof water pushes the reaction to completion. Soap is made by the alkaline hy- An aqueous solution of sodium hydroxide or potassium hydroxide also drolysis of naturally occurring can be used to hydrolyze esters.Since many estersdo not dissolve in water, triglycerides (triesters of glycerol a solvent such as ethanol is added to make the solution homogeneous.The and fatty acids). The process of reaction mixture is usuallyheated. All the ester is converted to products. At making soap is called saponifica- the end of the reaction. the carboxvlic acid is in solution as its sodium or (Latin): tion after sapon soap. potassium salt: Once hydrolyzed, the fatty acid salts are purified, dried, and o o shaped into bars. Additional NaoH il ingredients such as dyes for coloq cH3-e-ocH2cH3 + NaoH , cH3-c-O Na- * HOCH2CH3 perfume for odor, and antiseptics Ethyl acetate Sodium Sodiumacetate Ethanol may be added to the soap. hydroxide If the reaction mixture is acidified, the carboxylic acid is formed: o o il cH3-c-o-Na* + HCI -------CH3-C-OH + NaCl Sodium acetate Acetic acid EXAMPTEI4.6 Hydrolysisof an ester Write the structure and name the products of the acid-catalyzedhydrolysis of isobutyl propanoate. sotuTroN The ester is hydrolyzed to an alcohol and an acid: cH3cH2coocH2cHCH3+ H2o -I9! cn.cH2cooH + HOCH2CHCH3 J". J", The alkyl part of the narne, isobutyl,comes from the alcohol, isobutyl alco- hol The acidts propynotc acid. ,,: PRACTICEEXERCISE t4.9 ' oftheexpectedproducts. ,. (a) cH3cH2coocH2cH3+ NaoH to' ."..oo-O +KoH 448 CHAPTER14 Acidsand Their Derivatives 14.9 Phosphoricocids, anhydrides, ond esfers AIMS: To nome ond drow structuresof the voriousforms of phosphoricocid ond phosphateesfers' To write equotions for the hydrolysisof phosphoricocid onhydrides.To describeo phosphorylgroup ond write on equotion showingo phosphorylotionreoction. Recall that phosphorus is one of the important elements found in the Focus human body. This phosphorus is present as phosphate ions, as phosphoric The chemistry of carboxylic acid anhydrides,and as phosphateesters. andphosphoric acids is similar. Phosphoric acid is a moderately strong acid' It differs from carboxylic acids becauseit contains three ionizable protons; a carboxyl function con- tains only one. The various degreesof ionization are o o o o HO-P-OH HO-P-O HO-P-O o-P-o- I I I I OH OH o- o- Predominant About equal This form speciesat amounts of these tlvo predominates pH values forms exist at pH values lessthan 2 at pH 7.0 greater than I 1 As shornm,the ionization state varies with the pH of the solution. AtpH 7.0' the singly and doubly charged phosphate ions are present in about equal amounts. In biochemistry the sy'rnbolP; (inorganic phosphate) is often used to represent all possible ionization states of phosphoric acid in solu- tion at pH 7.0. Anhydrides of phosphoric acid Like carboxylic acids, phosphoric acid can be dehydrated to form the anhy- dride. Unlike carboxylic acids, however, phosphoric acid can form more than one anhydride bond due to its multiple hydroxyl groups. The simplest anhydride of phosphoric acid is pyrophosphoric acid. The various ionized forms of pyrophosphoric acid (diphosphate ions) at pH 7.0 are often abbre- viated PP; (inorganic pyrophosphate): Anhydride tTr1l."'j'"lo o o oo il tl II t"ut, HO-P-OH + HO-P-OH Ho-ir-o-ir-oH + H2o II OH OH OH OH Twomolecules of Pyrophosphoricacid phosphoricacid Pyrophosphoric acid can react with yet another molecule of phosphoric 14.9 PhosphoricAcids, Anhydrides, and Esters 449 acid by elimination of water to form triphosphoric acid. Triphosphoric acid is sometimes representedin its various ionized forms (triphosphate ions) at pH 7.0 as PPP;(inorganic triphosphate): Adrydride functional groups ooo ooo llllrl H"ut, lltl HO-P-O-P-OH + HO-P-OH Ho-ir-o-p-o-i-o" + H2o lll OH OH OH oH oH d" Pyrophosphoric Phosphoric Triphosphoric acid acid acid Pyrophosphoric acid and triphosphoric acid are the major anhydrides of phosphoric acid. Remember that phosphoric acid anhydrides contain two functional groups: the anhydride and hydroxyl groups. Both these func- tional groups are important in the reactions we will be discussing. Esters of phosphoric acid Phosphate esters are important Just as carboxylic acids and alcohols react to form carboxylic acid esters, intermediates in many metabolic phosphoric acid can react with alcohols to form phosphate esters.Because pathways. In Chapter 24, for ex- phosphoric acid has three hydroxyl groups, one, two, or all three of these ample, we will seethat the ester groups can be esterified to form monoesters, diesters, or triesters. This is glyceraldehyde-3-phosphate plays shovrmfor the reaction of phosphoric acid with methanol. an important role in the energy- producing breakdown of glucose. oo Ho-i-oH + cH3oH----- Ho-+-ocH3 + H-oH lr OH OH Monomethyl phosphate oo iltl HO-P-OH + 2CH.OH- HO-Y-OCH3 + 2H2O rl oH ocH3 Dimethyl phosphate o o II HO-P-OH + 3CH3OH- CH:O-P-OCH3 + 3H2O oH ocH3 Trimethyl phosphate The hydroxyl groups of phosphoric acid anhydrides may form esters with alcohols without breaking the anhydride bond. The following exam- ple shows a monoester, although more than one hydroxyl group could be 450 CHAPTER14 Acids and Their Derivatives esterified. Again, the methyl estersare used as typical examples: ooooo illlllllll HO-P-O-P-OCH3 HO-P-O-P-O-P-OCH3 tl ttl OH OH OH OH OH Monomethyl ester of Monomethyl ester of pyrophosphoric acid triphosphoric acid Ilydrolysis and phosphorylation We have seen that acetic anhydride can undergo cleavage by water in hydrolysis to form acetic acid (seeSec. 14.5) or react with alcohols to form esters in acylation (see Sec. 14.6).Phosphoric acid anhydrides can do the same. Upon hydrolysis, phosphoric acid anhydrides are converted back to phosphoric acid: 'is5#"' I- oo o/ o llll /ll HO-P-O-P-OH + H-OH ----_ HO-P-OH + HO-P-OH ll OH OH OH OH Pyrophosphoricacid Two moleculesof phosphoricdcid ooo o ililll HO-P-O-P-O-P-OH * HrO + 3HO-i-OH tll I OH OH OH OH Triphosphoricacid Three molecules ofphosphoric acid We can consider the hydrolysis of phosphoric acid anhydrides as the transfer of a phosphoryl grouir (-PO3H2) to water, just as the hydrolysis of acetic anhydride is a transfer of an acetyl group to water. And just as the transfer of an aceryl group to an alcohol or other functional group is called acetylation, transfer of aphosphoryl group to an alcohol or otherfunctional group is called phosphorylation. Here are two typical phosphorylation reactions: PhosphoryI I SIOUD oo o l- o illl |/ ll HO-P-O-P-OH + H-OCH3 - HO-P-OCH3 + HO-B-OH tl ll OH OH OH OH Pyrophosphoric acid Methanol Monomethyl Phosphoric phosphate acid ooo ooo illlll rrllll HO-P-O-P-O-P-OH + H-OCH: -_ HO-P-OCH3 + HO-P=O-P-OH tll I II OH OH OH OH OH OH Triphosphoric Methanol Monomethyl Pyrophosphoric l acid phosphate acid 14.10Esters of Nitricand NitrousAcids 451 Phosphorylation reactions of this type are enormously important in biochemistry. Adenosine triphosphate (ATP), a monoester of triphos- phoric acid, is nature's universal phosphorylating agent. The ATP in living systems is used to phosphorylate water, sugars, proteins, and nucleic acids.Transfers of energy in living organismscome from these phospho- rylation reactions. PRACTICEEXERCISE I4.IO Explain what is meant by the term phosphorylation. 14.10Esters of nitric ond nitrousocids AIM: To state the nomesond usesof importont estersof nitrous ond nitric ocids. Alcohols react with nitric acid (HNO3) and nitrous acid (HNOz) to produce Focus the alkyl nitrates and alkyl nitrites, respectively. Glycerol and nitric acid Nitrous and nitric acids form produce the ester glyceryl trinitrate, more commonly called nitroglycerin. important esters. /o CH,O-H HO N CH,O-N/ It\ lzo l) CHO-H + HO-N + [to-^o + 3H-oH \o \ 'o o o / / cH2o-H HO-N cH2o-N\ \o Glycerol Three molecules GlyceryI trinitrate Water ofnitric acid (nitroglycerin) Alfred Nobel (1833-1896)con- Nitroglycerin is an unstable, shock-sensitive,explosive, pale yellow liquid.
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  • THIOL OXIDATION a Slippery Slope the Oxidation of Thiols — Molecules RSH Oxidation May Proceed Too Predominates

    THIOL OXIDATION a Slippery Slope the Oxidation of Thiols — Molecules RSH Oxidation May Proceed Too Predominates

    RESEARCH HIGHLIGHTS Nature Reviews Chemistry | Published online 25 Jan 2017; doi:10.1038/s41570-016-0013 THIOL OXIDATION A slippery slope The oxidation of thiols — molecules RSH oxidation may proceed too predominates. Here, the maximum of the form RSH — can afford quickly for intermediates like RSOH rate constants indicate the order − − − These are many products. From least to most to be spotted and may also afford of reactivity: RSO > RS >> RSO2 . common oxidized, these include disulfides intractable mixtures. Addressing When the reactions are carried out (RSSR), as well as sulfenic (RSOH), the first problem, Chauvin and Pratt in methanol-d , the obtained kinetic reactions, 1 sulfinic (RSO2H) and sulfonic slowed the reactions down by using isotope effect values (kH/kD) are all but have (RSO3H) acids. Such chemistry “very sterically bulky thiols, whose in the range 1.1–1.2, indicating that historically is pervasive in nature, in which corresponding sulfenic acids were no acidic proton is transferred in the been very disulfide bonds between cysteine known to be isolable but were yet rate-determining step. Rather, the residues stabilize protein structures, to be thoroughly explored in terms oxidations involve a specific base- difficult to and where thiols and thiolates often of reactivity”. The second problem catalysed mechanism wherein an study undergo oxidation by H2O2 or O2 in was tackled by modifying the model acid–base equilibrium precedes the order to protect important biological system, 9-mercaptotriptycene, by rate-determining nucleophilic attack − − − structures from damage. Among including a fluorine substituent to of RS , RSO or RSO2 on H2O2. the oxidation products, sulfenic serve as a spectroscopic handle.
  • Hydrolysis and Atmospheric Oxidation Reactions of Perfluorinated Carboxylic Acid Precursors

    Hydrolysis and Atmospheric Oxidation Reactions of Perfluorinated Carboxylic Acid Precursors

    Hydrolysis and Atmospheric Oxidation Reactions of Perfluorinated Carboxylic Acid Precursors by Derek A. Jackson A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Graduate Department of Chemistry University of Toronto © Copyright by Derek A. Jackson 2013 Hydrolysis and Atmospheric Oxidation Reactions of Perfluorinated Carboxylic Acid Precursors Derek Andrew Jackson Doctor of Philosophy Department of Chemistry University of Toronto 2013 Abstract This dissertation explores a number of different environmentally relevant reactions that lead to the production of perfluorocarboxylic acids (PFCAs), a family of environmental pollutants that does not undergo any further degradation pathways. The compound perfluoro-2-methyl-3-pentanone (PFMP) is a new fire fighting fluid developed by 3M that is designed as a Halon replacement. The environment fate of PFMP with regards to direct photolysis, abiotic hydrolysis and hydration was determined using a combination of laboratory experiments and computational modeling. PFMP was found to undergo direct photolysis giving a lifetime of 4-14 days depending on latitude and time of year. Offline samples confirmed PFCA products and a mechanism was proposed. Polyfluorinated amides (PFAMs) are a class of chemicals produced as byproducts of polyfluorinated sulfonamide synthesis via electrochemical fluorination (ECF). Using synthesized standards of four model compounds, PFAMs were detected and quantified in a variety of legacy commercial materials synthesized by ECF. PFAMs were hypothesized to undergo biological hydrolysis reactions, suggesting their importance as historical PFOA precursors. ii The PFAMs were also investigated with regards to their environmental fate upon atmospheric oxidation. Using a smog chamber, the kinetics and degradation mechanisms of N- ethylperfluorobutyramide (EtFBA) were elucidated.