445
l4 Acidsand TheirDerivatives
CHAPTER
14,7Thioesters
AIM: To write on equotionfor the formotion of o thioester.
Focus
Thioesters are biologically
important.
The carboxylic esters we have seen so far are oxyestersbecause their carboxyl groups contain two oxygen atoms. In thioesters, the oxygen in the
link of an oxyesteris replacedby sulfur:
C-O-C
R-C
/
.o
or RCOOR
R-C
-R
\
/
o
or
RCOSR
S-R
Thioester
Oxyester
Thioesters can be prepared in the sameway as oxyesters.A thiol is used
instead of an alcohol:
R-C
o
/
+ RS-H
.+
OH
Thiol
Carboxylicacid
R-c/
t*
+ H-oH
Water
Thioester
If an acid anhydride is used in the esterification of a thiol, the processis an
acylation:
R-C
\ro
+ RS-H +
\
*-to
rAcvl qroup
(-"
//o
R-C
t*
+
R-C
\
'o
Thiol
Acidanhydride
Thioester
.roH
Carboxylic acid
Certain thioesters have biological significance. They transfer acyl
groups during the qmthesis and degradation of such substancesas carbohydrates, 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:
/
CH3-C.
\
o
+
HSCoA
OH
Acetic acid
CoenzyrneA
+CH3-C
//
t
o
+
HrO
aoo
Aceryl coenzymeA
Water
14.8 Esterhydrolysis
Estersmay be hydrolyzed to
their component acids and
alcohols.
AIM: To write an equotionfor the acid' or bose-catolyzed
hydrolysisof on ester.
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 ions :
o
tl
cH3-c-ocH2cH3
+ H-OH
H-
o
tl
cH3-c-OH
Soap is made by the alkaline hydrolysis of naturally occurring
triglycerides (triesters of glycerol
and fatty acids). The process of
making soap is called saponification after sapon (Latin): soap.
Once hydrolyzed, the fatty acid
salts are purified, dried, and
shaped into bars. Additional
ingredients such as dyes for coloq
perfume for odor, and antiseptics
may be added to the soap.
+ HOCH2CHS
Aceticacid
Ethyl acetate
Ethanol
Sincethis hydrolysis processis reversible,a large excessof water pushes the
reaction to completion.
An aqueous solution of sodium hydroxide or potassium hydroxide also
can be used to hydrolyze esters.Sincemany estersdo not dissolve in water,
a solvent such as ethanol is added to make the solution homogeneous.The
reaction mixture is usuallyheated. All the ester is converted to products. At
the end of the reaction. the carboxvlic acid is in solution as its sodium or
potassium salt:
o
cH3-e-ocH2cH3
Ethyl acetate
+
NaoH
NaoH
o
il
, cH3-c-O
Na- * HOCH2CH3
Sodiumacetate
Sodium
hydroxide
Ethanol
If the reaction mixture is acidified, the carboxylic acid is formed:
o
o
il
+ HCI -------CH3-C-OH
cH3-c-o-Na*
Sodium acetate
E X A M P T EI 4 . 6
+ NaCl
Acetic acid
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:
+ H2o -I9!
cH3cH2coocH2cHCH3
J".
cn.cH2cooH + HOCH2CHCH3
J",
The alkyl part of the narne, isobutyl,comes from the alcohol, isobutyl alcohol The acidts propynotc acid.
t4.9
EXERCISE
,,: PRACTICE
'
,.
oftheexpectedproducts.
(a) cH3cH2coocH2cH3+ NaoH
to'
."..oo-O
+KoH
448
14 Acidsand Their Derivatives
CHAPTER
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.
Focus
The chemistry of carboxylic
andphosphoric acids is similar.
Recall that phosphorus is one of the important elements found in the
human body. This phosphorus is present as phosphate ions, as phosphoric
acid anhydrides,and as phosphateesters.
Phosphoric acid is a moderately strong acid' It differs from carboxylic
acids becauseit contains three ionizable protons; a carboxyl function contains only one. The various degreesof ionization are
HO-P-OH
HO-P-O
HO-P-O
I
I
I
o-
OH
OH
o
o-P-oI
o-
o
o
o
This form
predominates
at pH values
greater than I 1
About equal
amounts of these tlvo
forms exist
at pH 7.0
Predominant
speciesat
pH values
lessthan 2
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 solution at pH 7.0.
Anhydrides
of phosphoric
acid
Like carboxylic acids,phosphoric acid can be dehydrated to form the anhydride. 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 abbreviated PP; (inorganic pyrophosphate):
Anhydride
o
II
HO-P-OH
OH
tTr1l."'j'"lo
oo
o
+ HO-P-OH
OH
Twomoleculesof
phosphoricacid
t"ut,
il
tl
Ho-ir-o-ir-oH
II
OH
+ H2o
OH
acid
Pyrophosphoric
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
llllrl
HO-P-O-P-OH
lll
OH
+ HO-P-OH
OH
Pyrophosphoric
acid
ooo
lltl
H"ut,Ho-ir-o-p-o-i-o"
oH
OH
Phosphoric
acid
oH
+ H2o
d"
Triphosphoric 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 functional groups are important in the reactions we will be discussing.
Esters of phosphoric acid
Phosphate esters are important
intermediates in many metabolic
pathways. In Chapter 24, for example, we will seethat the ester
glyceraldehyde-3-phosphate plays
an important role in the energyproducing breakdown of glucose.
Just as carboxylic acids and alcohols react to form carboxylic acid esters,
phosphoric acid can react with alcohols to form phosphate esters.Because
phosphoric acid has three hydroxyl groups, one, two, or all three of these
groups can be esterified to form monoesters, diesters, or triesters. This is
shovrmfor the reaction of phosphoric acid with methanol.
oo
Ho-i-oH
lr
+ cH3oH----- Ho-+-ocH3 + H-oH
OH
OH
Monomethyl
phosphate
oo
iltl
HO-P-OH
rl
oH
+ 2CH.OH-
HO-Y-OCH3 + 2H2O
ocH3
Dimethyl
phosphate
o
II
HO-P-OH
oH
o
+ 3CH3OH-
CH:O-P-OCH3 + 3H2O
ocH3
Trimethyl
phosphate
The hydroxyl groups of phosphoric acid anhydrides may form esters
with alcohols without breaking the anhydride bond. The following example shows a monoester, although more than one hydroxyl group could be
450
14 Acids and Their Derivatives
CHAPTER
esterified. Again, the methyl estersare used as typical examples:
ooooo
illlllllll
HO-P-O-P-OCH3
tl
OH
HO-P-O-P-O-P-OCH3
ttl
OH
OH
Monomethyl ester of
triphosphoric acid
Monomethyl ester of
pyrophosphoric acid
Ilydrolysis
OH
OH
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
llll
+ H-OH
HO-P-O-P-OH
OH
o/
/ll
----_ HO-P-OH
+ HO-P-OH
ll
OH
OH
OH
Two moleculesof phosphoricdcid
Pyrophosphoricacid
ooo
ililll
HO-P-O-P-O-P-OH
tll
OH
o
OH
o
* HrO +
3HO-i-OH
I
OH
OH
Three molecules
ofphosphoric acid
Triphosphoricacid
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
o l-
oo
illl
HO-P-O-P-OH
tl
OH
OH
OH
Triphosphoric
acid
HO-P-OCH3
ll
OH
OH
Pyrophosphoric acid
ooo
illlll
HO-P-O-P-O-P-OH
tll
+ H-OCH3 -
|/
Monomethyl
phosphate
Methanol
o
ll
+ HO-B-OH
OH
Phosphoric
acid
ooo
+ H-OCH:
OH
Methanol
-_
rrllll
HO-P-OCH3
+ HO-P=O-P-OH
OH
OH
I
Monomethyl
phosphate
I I
OH
Pyrophosphoric
acid
l
of Nitricand NitrousAcids
14.10Esters
451
Phosphorylation reactions of this type are enormously important in
biochemistry. Adenosine triphosphate (ATP), a monoester of triphosphoric acid, is nature's universal phosphorylating agent. The ATP in living
systems is used to phosphorylate water, sugars, proteins, and nucleic
acids.Transfersof energy in living organisms come from these phosphorylation reactions.
PRACTICE
EXERCISE
I4.IO
Explain what is meant by the term phosphorylation.
14.10Estersof nitric ond nitrousocids
AIM: To state the nomesond usesof importont estersof nitrous
ond nitric ocids.
Focus
Nitrous and nitric acids form
important esters.
Alcohols react with nitric acid (HNO3) and nitrous acid (HNOz) to produce
the alkyl nitrates and alkyl nitrites, respectively. Glycerol and nitric acid
produce the ester glyceryl trinitrate, more commonly called nitroglycerin.
CH,O-H
HO
t\
I
lzo
+
CHO-H
cH2o-H
Glycerol
Alfred Nobel (1833-1896)conducted experiments to stabilize
nitroglycerin on a lake barge. This
came after the factory in which he
manufacturedn itroglycerin was
destroyed in an explosion and he
was forbidden by the Swedish
government to rebuild. Upon his
death, he left the bulk of his fortune to establish the Nobel prizes.
N
HO-N
HO-N
/o
\o
o
CH,O-N/
+
/
\o
Three molecules
ofnitric acid
l)
[to-^o
cH2o-N\
\ 'o
/
+ 3H-oH
o
GlyceryI trinitrate
(nitroglycerin)
Water
Nitroglycerin is an unstable, shock-sensitive,explosive,pale yellow liquid.
It was first made in 1846 by the Italian chemist Ascanio Sobrero
(fBfZ-lBBB).The Swedishchemist Alfred Nobel (1833-1896)perfected its
synthesis in the mid-l9th century and devised a safe method for handling
it. Nobel mixed nitroglycerin with kieselghur;a claylike absorbent material.
The result was dynamite, an explosive that is not sensitive to shock. Since
its development, dlmamite has been important in the construction of
canals,dams, and roads. It also has played a major role in warfare.
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
14 AcidsandTheirDerivatives
CHAPTER
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 functional group (-CO2H). Fatty acids (straight-chain
saturated and unsaturated aliphatic carboxylic
acids) are widely distributed in nature, as are many
other carboxylic acids.Benzoic acid is the parent aromatic carboxylic acid. Fatty acids containing up to
four carbons are completely soluble in water. Carboxylic acids of higher molar mass are less soluble,
but they tend to form monomolecular layers at water
surfacesand micelles within water. Carboxylic acids
are weak acids and ionize only to a slight extent in
water. The acidity increasesif the acid molecules
contain electron-withdrawing substituents. Like
other acids, carboxylic acids can be neutralized by
basesto give salts. Soapsare the alkali metal salts of
long-chain carboxylic acids. Detergents are often
Caralkali metal salts of sulfonic acids (RSO.3H).
boxylic acids may be preparedby either the oxidation
of primary alcohols or the oxidation of aldehydes.
Anhydrides (RCO2COR)and esters (RCOzR)are
important derivatives of carboxylic acids. Anhy-
drides, formed by the dehydration of carboxylic
acids,form esterswhen they react with an alcohol or
a phenol, as in the preparation of aspirin. Estersalso
can be prepared by the reaction of a carboxylic acid
and an alcohol. Many naturally occurring esters
impart pleasant odors and flavors to fruits. Polyesters (pol1'rnericesters)can be made into synthetic
fibers. Esters can be converted to the component
carboxylic acid and alcohol by hydrolysis in acidic or
basic solution. Certain thioesters,especiallyesters
of the thiol coen4rme A, are biologically important.
Esters and anhydrides of phosphoric acid are also
biologically important as agents that can transfer
phosphoryl groups (-PO3H). AIB an ester of the
phosphoric anhydride triphosphoric acid, is the
major phosphorylating agent of living cells.Estersof
inorganic acids such as nitric and nitrous acids have
such varied applications as explosives (nitroglycerin) and medications for the relief of angina pectoris (isoamyl nitrite).
#tr ffi€&€39*Hg
str#e#€&#Y
Herearethe reactionsof carboxylicacidsand inorganicacidsand
their derivativesdescribedin this chapter.
Acids
Carboxylic
l. Preparation
of carboxylicacids:
o
HO
I
oddation'
n-c-u
R-C-OH
Oxidation,
n_t_OH
I
H
Carboxylic acid
Aldehyde
Primary alcohol
2. Neutralization of carboxylic acids:
o
o
R-C-OH
LarDoxyrc
acid
+ OH
Base
------ R-C-O
+ H-OH
Carboxylate
ion
Water