Vollhardt  Capítulo 9 (Éters)
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Vollhardt Capítulo 9 (Éters)


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C H A P T E R
Further Reactions of
Alcohols and the
Chemistry of Ethers
N I N E
Do you remember the fi zzing that occurred when you (or your teacher) dropped a pellet of sodium into water? The violent reaction that you observed was due to the conver-
sion of the metal and water into NaOH and H2 gas. Alcohols, which 
can be regarded as \u201calkylated water\u201d (Section 8-2), undergo the 
same reaction, albeit less vigorously, to give NaOR and H2. This 
chapter will describe this and further transformations of the hydroxy 
substituent.
 Figure 9-1 depicts a variety of reaction modes available to alco-
hols. Usually at least one of the four bonds marked a, b, c, or d is 
cleaved. In Chapter 8 we learned that oxidation to aldehydes and 
ketones breaks bonds a and d. We found that the use of this reaction in combination with 
additions of organometallic reagents provides us with the means of preparing alcohols of 
considerable structural diversity.
 To further explore the reactions of alcohols, we start by reviewing their acidic and 
basic properties. Deprotonation at bond a furnishes alkoxides (Section 8-3), which are 
valuable both as strong bases and as nucleophiles (Section 7-8). Strong acids transform 
alcohols into alkyloxonium ions (Section 8-3), converting OH (a poor leaving group) into 
H2O (a good leaving group). Subsequently, bond b may break, thereby leading to substitu-
tion; or elimination can take place by cleavage of bonds b and c. We shall see that the 
carbocation intermediates arising from acid treatment of secondary and tertiary alcohols 
have a varied chemistry.
An introduction to the preparation of esters and their applications in synthesis is 
followed by the chemistry of ethers and sulfur compounds. Alcohols, ethers, and their 
sulfur analogs occur widely in nature and have numerous applications in industry and 
medicine.
Ethoxyethane (diethyl ether or 
simply \u201cether\u201d) was discovered 
as an anesthetic in 1846, 
prompting a newspaper 
headline exclaiming \u201cWe have 
conquered pain.\u201d The photo 
shows an ether inhaler from that 
period. It consists of a glass 
vessel that contains ether-
soaked sponges, connected to 
a facemask by tubing. Apart 
from its fl ammability, ether 
is fairly safe, but has the 
undesirable postanesthetic 
effects of headaches and 
nausea. It has been superseded 
by a host of more effective pain 
killing drugs, but is still popular 
in some developing nations.
O
334 C h a p t e r 9 F u r t h e r R e a c t i o n s o f A l c o h o l s a n d t h e C h e m i s t r y o f E t h e r s
9-1 Reactions of Alcohols with Base: Preparation of Alkoxides
As described in Section 8-3, alcohols can be both acids and bases. In this section, we shall 
review the methods by which the hydroxy group of alcohols is deprotonated to furnish their 
conjugate bases, the alkoxides.
Strong bases are needed to deprotonate alcohols completely
To remove a proton from the OH group of an alcohol (Figure 9-1, cleavage of bond a), we 
must use a base stronger than the alkoxide. Examples include lithium diisopropylamide (Sec-
tion 7-8), butyllithium (Section 8-7), and alkali metal hydrides (Section 8-6, Exercise 8-4), 
such as potassium hydride, KH. Such hydrides are particularly useful because the only by-
product of the reaction is hydrogen gas.
CH3OH
Three Ways of Making Methoxide from Methanol
pKa\ufffd15.5 pKa\ufffd 40
K \ufffd1024.5
Li\ufffd\ufffdNCH(CH3)2
CH(CH3)2
CH3OH CH3O\ufffdK\ufffdK\ufffdH\ufffd H H
CH3O\ufffdLi\ufffd\ufffd HNCH(CH3)2\ufffd
A
CH(CH3)2
A
O
CH3OH
K \ufffd1034.5
CH3CH2CH2CH2Li CH3O\ufffdLi\ufffd\ufffd
\ufffd \ufffd
CH3CH2CH2CH2H\ufffd
K \ufffd1022.5
pKa\ufffd15.5 pKa\ufffd 50
pKa\ufffd15.5 pKa\ufffd 38
Lithium diisopropylamide
Potassium
hydride
Butyllithium
A
OOC
A
A
OO OCH HO
H
A
OOC
A
A
OOCH O\ufffd
HDeprotonation
Substitution
Elimination
Oxidation
a
A
OOC
A
A
OO OCH HO
H
b
A
OOC
A
A
OO OCH HO
H
c
Alkoxide
A
OOC
A
A
OOCH X
H
Haloalkane and
other alkane
derivatives
Alkenes
A
OOC
A
A
OO OCH HO
H
d a
b
A
C
A
OO H
Aldehydes
and ketones
B
C
H
CH
H
E
E
C
O
CE N
Figure 9-1 Four typical reaction 
modes of alcohols. In each mode, 
one or more of the four bonds 
marked a \u2013 d are cleaved (wavy line 
denotes bond cleavage): (a) de-
protonation by base; (b) proton-
ation by acid followed by uni- or 
bimolecular substitution; (b, c) 
elimination; and (a, d) oxidation.
Sodium reacts with water vigor-
ously, releasing hydrogen gas.
 C h a p t e r 9 335
Alkali metals also deprotonate alcohols \u2014 but by reduction of H1
Another common way of obtaining alkoxides is by the reaction of alcohols with alkali 
 metals, such as lithium. Such metals reduce water \u2014 in some cases, violently \u2014 to yield alkali 
metal hydroxides and hydrogen gas. When the more reactive metals (sodium, potassium, 
and cesium) are exposed to water in air, the hydrogen generated can ignite spontaneously 
or even detonate.
H OH 2 M\ufffd\ufffdOH2 M (Li, Na, K, Cs) H2O \ufffd \ufffd2
The alkali metals act similarly on the alcohols to give alkoxides, but the transformation is 
less vigorous. Here are two examples.
2 CH3CH2O\ufffdNa\ufffd H22 Na2 CH3CH2OH \ufffd \ufffd
2 (CH3)3CO\ufffdK\ufffd H22 K2 (CH3)3COH \ufffd \ufffd
Alkoxides from Alcohols and Alkali Metals
The reactivity of the alcohols used in this process decreases with increasing substitution, 
methanol being most reactive and tertiary alcohols least reactive.
Relative Reactivity of ROH with Alkali Metals
R 5 CH3 . primary . secondary . tertiary
Decreasing reactivity
2-Methyl-2-propanol reacts so slowly that it can be used to safely destroy potassium resi-
dues in the laboratory.
What are alkoxides good for? We have already seen that they can be useful reagents in 
organic synthesis. For example, the reaction of hindered alkoxides with haloalkanes gives 
elimination.
K\ufffdBr\ufffdCH3CH2CH2CH2Br CH3CH2CH CH2 (CH3)3COH
(CH3)3CO\ufffdK\ufffd, (CH3)3COH 
E2
\ufffd \ufffdP
Less branched alkoxides attack primary haloalkanes by the SN2 reaction to give ethers. This 
method is described in Section 9-6.
In Summary A strong base will convert an alcohol into an alkoxide by an acid-base reac-
tion. The stronger the base, the more the equilibrium is displaced to the alkoxide side. Alkali 
metals react with alcohols by reduction to generate hydrogen gas and an alkoxide. This 
process is retarded by steric hindrance.
9-2 Reactions of Alcohols with Strong Acids: Alkyloxonium Ions 
in Substitution and Elimination Reactions of Alcohols
We have seen that heterolytic cleavage of the O \u2013 H bond in alcohols is readily achieved 
with strong bases. Can we break the C \u2013 O linkage (bond b, Figure 9-1) as easily? Yes, but 
now we need acid. Recall (Section 2-2) that water has a high pKa (15.7): It is a weak acid. 
Consequently, hydroxide, its conjugate base, is an exceedingly poor leaving group. For 
alcohols to undergo substitution or elimination reactions, the OH must fi rst be converted 
into a better leaving group.
9 - 2 R e a c t i o n s o f A l c o h o l s w i t h S t r o n g A c i d s
Exercise 9-1
We shall encounter later many reactions that require catalytic base, for example, catalytic sodium 
methoxide in methanol. Assume that you would like to make such a solution containing 10 mmol of 
NaOCH3 in 1 liter of CH3OH. Would it be all right simply to add 10 mmol of NaOH to the solvent? 
(Caution: Simply comparing pKa values (Table 2-2) is not enough. Hint: See Section 2-2.)
336 C h a p t e r 9 F u r t h e r R e a c t i o n s o f A l c o h o l s a n d t h e C h e m i s t r y o f E t h e r s
Haloalkanes from primary alcohols and HX: Water can be a 
leaving group in SN2 reactions
The simplest way of turning the hydroxy substituent in alcohols into a good leaving group 
is to protonate the oxygen to form an alkyloxonium ion. Recall (Section 8-3) that this 
process ties up one of the oxygen lone pairs by forming a bond to a proton. The positive 
charge therefore resides on the oxygen atom. Protonation changes OH from a bad leaving 
group into neutral water, a good leaving group.
This reaction is reversible and, under normal conditions, the equilibrium lies on the side 
of unprotonated