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Home , Pyrophosphoric acid, Thioester, Thiol, Triphosphoric acid

445 CHAPTERl4 Acidsand TheirDerivatives

14,7Thioesters AIM: To write on equotion for the formotion of o .

The carboxylic we have seen so far are oxyestersbecause their car- Focus boxyl groups contain two atoms. In , the oxygen in the Thioesters are biologically C-O-C link of an oxyesteris replacedby : 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 is used instead of an : o / R-C + RS-H .+ R-c/ + H-oH t* OH Carboxylicacid Thiol Thioester Water If an 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 Certain thioesters have biological significance. They transfer acyl groups during the qmthesis and degradation of such substancesas carbo- hydrates, amino , and fatty acids. Acetyl 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 . Estersmay be hydrolyzed to their component acids and If an ester is heated with water for severalhours, usually very little happens. . In strong acid solutions, however, ester hydrolysis is rapid becauseit is cat- I4.8 EsterHydrolysis 447

alyzed by hydro gen : o o tl H- tl cH3-c-ocH2cH3 + H-OH cH3-c-OH + HOCH2CHS Ethyl acetate Aceticacid Sincethis hydrolysis processis reversible,a large excessof water pushes the reaction to completion. Soap is made by the alkaline hy- An aqueous solution of 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 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 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 , 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 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 is one of the important elements found in the Focus human body. This phosphorus is present as ions, as phosphoric The chemistry of carboxylic acid anhydrides,and as phosphateesters. andphosphoric acids is similar. 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 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 . The various ionized forms of pyrophosphoric acid (diphosphate ions) at pH 7.0 are often abbre- viated PP; (inorganic ):

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 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 . 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 to water. And just as the transfer of an aceryl group to an alcohol or other 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. (ATP), a monoester of triphos- phoric acid, is nature's universal phosphorylating agent. The ATP in living systems is used to phosphorylate water, sugars, , 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 and , 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. ducted experiments to stabilize It was first made in 1846 by the Italian chemist Ascanio Sobrero nitroglycerin on a lake barge. This (fBfZ-lBBB).The Swedishchemist Alfred Nobel (1833-1896)perfected its came after the factory in which he synthesis in the mid-l9th century and devised a safe method for handling manufacturedn itroglycerin was it. Nobel mixed nitroglycerin with kieselghur;a claylike absorbent material. destroyed in an explosion and he The result was dynamite, an explosive that is not sensitive to shock. Since was forbidden by the Swedish its development, dlmamite has been important in the construction of government to rebuild. Upon his death, he left the bulk of his for- canals, dams, and roads. It also has played a major role in warfare. tune to establish the Nobel prizes. Nitroglycerin and isoamyl nitrite, an ester of nitrous acid, have been used as drugs for over a hundred years.

CHa. CHCH2CH2-O-N:O CH. Isoamyl nitrite Both these esters,when inhaled or taken as tablets, produce immediate relaxation of the smooth muscles of the body and expansion of the blood 452 CHAPTER14 Acidsand Their Derivatives

vessels.They are used to treat people with angina pectoris-chest pains caused by an insufficient supply of oxygen to the heart muscle. Isoamyl nitrite is also the active ingredient in the widely abused drug called "poppers."

$$Jr# ffi&ffiY Carboxylic acids (RCOzH)contain the carboxyl func- drides, formed by the dehydration of carboxylic tional group (-CO2H). Fatty acids (straight-chain acids, form esterswhen they react with an alcohol or saturated and unsaturated aliphatic carboxylic a , as in the preparation of aspirin. Estersalso acids) are widely distributed in nature, as are many can be prepared by the reaction of a carboxylic acid other carboxylic acids.Benzoic acid is the parent aro- and an alcohol. Many naturally occurring esters matic carboxylic acid. Fatty acids containing up to impart pleasant and flavors to fruits. Poly- four are completely soluble in water. Car- esters (pol1'rnericesters) can be made into synthetic boxylic acids of higher molar mass are less soluble, fibers. Esters can be converted to the component but they tend to form monomolecular layers at water carboxylic acid and alcohol by hydrolysis in acidic or surfacesand micelles within water. Carboxylic acids basic solution. Certain thioesters,especially esters are weak acids and ionize only to a slight extent in of the thiol coen4rme A, are biologically important. water. The acidity increasesif the acid molecules Esters and anhydrides of phosphoric acid are also contain electron-withdrawing . Like biologically important as agents that can transfer other acids, carboxylic acids can be neutralized by phosphoryl groups (-PO3H). AIB an ester of the basesto give salts. Soapsare the salts of phosphoric anhydride triphosphoric acid, is the long-chain carboxylic acids. Detergents are often major phosphorylating agent of living cells. Estersof alkali metal salts of sulfonic acids (RSO.3H).Car- inorganic acids such as nitric and nitrous acids have boxylic acids may be prepared by either the oxidation such varied applications as explosives (nitroglyc- of primary alcohols or the oxidation of . erin) and medications for the relief of angina pec- Anhydrides (RCO2COR)and esters (RCOzR)are toris (isoamyl nitrite). important derivatives of carboxylic acids. Anhy- str#e#€&#Y#tr ffi€&€39*Hg Hereare the reactionsof carboxylicacids and inorganicacids and their derivativesdescribed in this chapter.

CarboxylicAcids l. Preparationof carboxylicacids:

HO o I oddation Oxidation, R-C-OH ' n-c-u n_t_OH I H

Primary alcohol Carboxylic acid 2. Neutralization of carboxylic acids: o o R-C-OH + OH ------R-C-O + H-OH

LarDoxyrc Base Carboxylate Water acid