Vollhardt  Capítulo 7 (Haloalcanos 2)
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Vollhardt Capítulo 7 (Haloalcanos 2)


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C H A P T E R
Further Reactions
of Haloalkanes
S E V E N
We have learned that the SN2 displacement process is an important reaction pathway for haloalkanes. But is it the only mechanism for 
displacement available? Or are there other, fundamen-
tally different types of transformations that haloal-
kanes undergo? In this chapter, we shall see that 
haloalkanes can indeed follow reaction pathways other 
than SN2 displacement, especially if the haloalkanes 
are tertiary or secondary. In fact, bimolecular substitu-
tion is only one of four possible modes of reaction. 
The other three modes are unimolecular substitution 
and two types of elimination processes. The elimina-
tion processes give rise to double bonds through loss 
of HX and serve as our introduction into the prepara-
tion of multiply bonded organic compounds.
7-1 Solvolysis of Tertiary and Secondary Haloalkanes
We have learned that the rate of the SN2 reaction diminishes drastically when the reacting 
center changes from primary to secondary to tertiary. These observations, however, pertain 
only to bimolecular substitution. Secondary and tertiary halides do undergo substitution, 
but by another mechanism. In fact, these substrates transform readily, even in the presence 
of weak nucleophiles, to give substitution products.
For example, when 2-bromo-2-methylpropane (tert-butyl bromide) is mixed with water, it 
is rapidly converted into 2-methyl-2-propanol (tert-butyl alcohol) and hydrogen bromide. Water 
is the nucleophile here, even though it is poor in this capacity. Such a transformation, in which 
a substrate undergoes substitution by solvent molecules, is called solvolysis, such as methano-
lysis, ethanolysis, and so on. When the solvent is water, the term hydrolysis is applied.
[ ]
\u161
CH3
Poor nucleophile
yet fast reaction!
CH3
H OH
Relatively fast
2-Bromo-2-methylpropane
(tert-Butyl bromide)
2-Methyl-2-propanol
(tert-Butyl alcohol)
An Example of Solvolysis: Hydrolysis
CH3CBr \ufffd HBr\ufffd
A
A
CH3
CH3
CH3COH
A
A
O
\u161
\u161 \u161
\u161
\u161
\u161
\u161
\u161
\u161
Medicinal chemists use many 
reactions to explore structure-
activity relationships in 
physio logically active compounds. 
Above, the bromocyclohexyl 
substituent to a b-lactam is 
converted to a cyclohexenyl 
group by elimination of HBr. 
b-Lactams are four-membered 
ring amides featured in the 
structure of many antibiotics, such 
as penicillin and cephalosporin, 
and their modifi cation is essential 
in combating drug resistance. 
The photo shows Petri dish 
cultures of two strains of 
Staphylococcus aureus bacteria 
(opaque and grey), an organism 
that causes boils, abscesses, 
and urinary tract infections. At 
left, one bacterial strain shows 
sensitivity to penicillin (white 
pellet) as indicated by the clear 
zone of inhibited growth around 
it. At right, a second strain of 
bacteria shows resistance to 
the drug and its growth is not 
inhibited.
Unimolecular Substitution and 
Pathways of Elimination
:Base
O
ON N
Br
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252 C h a p t e r 7 F u r t h e r R e a c t i o n s o f H a l o a l k a n e s
2-Bromopropane is hydrolyzed similarly, albeit much more slowly, whereas 1-bromopropane, 
bromoethane, and bromomethane are unchanged under these conditions.
CH3
H
H OH
Relatively slow
2-Bromopropane
(Isopropyl bromide)
2-Propanol
(Isopropyl alcohol)
Hydrolysis of a Secondary Haloalkane
CH3CBr \ufffd HBr\ufffd
A
A
CH3
H
CH3COH
A
A
O\u161
\u161\u161
\u161
\u161
\u161
\u161
\u161\u161\u161
Solvolysis also takes place in alcohol solvents.
CH3
CH3OH
Solvent
CH3
2-Chloro-
2-methylpropane
2-Methoxy-
2-methylpropane
Solvolysis of 2-Chloro-2-methylpropane in Methanol
CH3CCl \ufffd HCl\ufffd
A
A
CH3
CH3
CH3COCH3
A
A
\u161
\u161
\u161\u161
\u161
\u161
\u161
\u161
\u161
\u161
Solvolysis\u2014the
solvent is also
the nucleophile
The relative rates of reaction of 2-bromopropane and 2-bromo-2-methylpropane with 
water to give the corresponding alcohols are shown in Table 7-1 and are compared with 
the corresponding rates of hydrolysis of their unbranched counterparts. Although the process 
gives the products expected from an SN2 reaction, the order of reactivity is reversed from 
that found under typical SN2 conditions. Thus, primary halides are very slow in their reac-
tions with water, secondary halides are more reactive, and tertiary halides are about 1 mil-
lion times as fast as primary ones.
These observations suggest that the mechanism of solvolysis of secondary and, espe-
cially, tertiary haloalkanes must be different from that of bimolecular substitution. To under-
stand the details of this transformation, we shall use the same methods that we used to study 
the SN2 process: kinetics, stereochemistry, and the effect of substrate structure and solvent 
on reaction rates.
Reminder
Nucleophile: red
Electrophile: blue
Leaving group: green
REACTION
Methyl and Primary 
Haloalkanes: 
Unreactive in Solvolysis
CH3Br
CH3CH2Br
CH3CH2CH2Br
Essentially no reaction with H2O 
at room temperature
7-2 Unimolecular Nucleophilic Substitution
In this section, we shall learn about a new pathway for nucleophilic substitution. Recall that 
the SN2 reaction
\u2022 Has second-order kinetics
\u2022 Generates products stereospecifi cally with inversion of confi guration
\u2022 Is fastest with halomethanes and successively slower with primary and secondary 
halides
\u2022 Does not take place with tertiary substrates at all
Exercise 7-1
Whereas compound A (shown in the margin) is completely stable in ethanol, B is rapidly converted 
into another compound. Explain.
Br
B
H3C A AA A
A
H3C CH2Br
Table 7-1
Relative Reactivities of 
Various Bromoalkanes 
with Water
 Relative
Bromoalkane rate
CH3Br 1
CH3CH2Br 1
(CH3)2CHBr 12
(CH3)3CBr 1.2 3 10
6
In
cr
ea
si
ng
 r
ea
ct
iv
ity
in
 s
ol
vo
ly
si
s
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Podemos inferir que o carbocátion não seria estabilizado, e que portanto a sobstituição ou não ocorre, ou ocorre em Sn2 (eliminação E1 ou E2 ainda não foi tratada).
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Mesmo que a água não seja um bom nucleófilo, ela ainda pode reagir com tais compostos pois o carbocárion formado é melhor estabilizado, fazendo com que, portanto, possa ser realizada uma Sn1
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A possúi:nullnull1. impedimento estérico.nullnull2. carbono primário ligado ao grupo de partidanullnullnullnull...enquanto B:nullnull1. é um carbono terceario, e, portanto, forma um carbocárion mais estabilizado no caso da saída do bromo.nullnull2. não sofre tamanho impedimento estérico.
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 C h a p t e r 7 253
In contrast, solvolyses
\u2022 Follow a fi rst-order rate law
\u2022 Are not stereospecifi c
\u2022 Are characterized by the opposite order of reactivity
Let us see how these fi ndings can be accommodated mechanistically.
Solvolysis follows \ufb01 rst-order kinetics
In Chapter 6, the kinetics of reaction between halomethanes and nucleophiles revealed a 
bimolecular transition state: The rate of the SN2 reaction is proportional to the concentration 
of both ingredients. Similar studies have been carried out by varying the concentrations of 
2-bromo-2-methylpropane and water in formic acid (a polar solvent of very low nucleophi-
licity) and measuring the rates of solvolysis. The results of these experiments show that the 
rate of hydrolysis of the bromide is proportional to the concentration of only the starting 
halide, not the water.
Rate 5 k[(CH3)3CBr] mol L
21 s21
What does this observation mean? First, it is clear that the haloalkane has to undergo 
some transformation on its own before anything else takes place. Second, because the fi nal 
product contains a hydroxy group, water (or, in general, any nucleophile) must enter the 
reaction, but at a later stage and not in a way that will affect the rate law. The only way 
to explain this behavior is to postulate that any steps that follow the initial reaction of the 
halide are relatively fast. In other words, the observed rate is that of the slowest step in 
the sequence: the rate-determining step. It follows that only those species