Vollhardt  Capítulo 6 (Haloalcanos)
36 pág.

Vollhardt Capítulo 6 (Haloalcanos)


DisciplinaQuímica Orgânica II1.672 materiais36.225 seguidores
Pré-visualização16 páginas
the previously mentioned SN2 option. In this example, the internal displacement 
produces two species (the cyclic product and chloride ion) from one, giving rise to an increase in 
energy dispersal and therefore a favorable entropy change.
Table 6-7
Relative Rates of Reaction of 
Various Nucleophiles with 
Iodomethane in Methanol 
(Protic Solvent)
 Relative
Nucleophile rate
CH3OH 1
NO3
2 ,32
F2 500
 O
 B
CH3CO
2 20,000
Cl2 23,500
(CH3CH2)2S 219,000
NH3 316,000
CH3SCH3 347,000
N3
2 603,000
Br2 617,000
CH3O
2 1,950,000
CH3SeCH3 2,090,000
CN2 5,010,000
(CH3CH2)3As 7,940,000
I2 26,300,000
HS2 100,000,000
In
cr
ea
si
ng
 n
uc
le
o
p
hi
lic
it
y
6 - 8 S t r u c t u r e a n d S N 2 R e a c t i v i t y : T h e N u c l e o p h i l e
Try It Yourself
Gentle warming of a solution of 5-chloro-1-pentanamine, Cl(CH2)5NH2, in ethoxyethane (diethyl-
ether, CH3CH2OCH2CH3) solvent causes precipitation of a white solid. This solid is found to be 
a salt. Suggest a structure for this compound and explain its formation.
3157T_ch06_215-250.indd Page 239 4/18/09 7:53:35 AM user-s1723157T_ch06_215-250.indd Page 239 4/18/09 7:53:35 AM user-s172 /Users/user-s172/Desktop/Tempwork/Don'tDelete_Job/FREE036:Vollhardt/FREE036-/Users/user-s172/Desktop/Tempwork/Don'tDelete_Job/FREE036:V
Admin
Highlight
Admin
Rectangle
Admin
Highlight
Admin
Highlight
Admin
Highlight
240 C h a p t e r 6 P r o p e r t i e s a n d R e a c t i o n s o f H a l o a l k a n e s
of a range of nucleophiles relative to that of the very weakly nucleophilic methanol (arbi-
trarily set at 1). We can confi rm the validity of the conclusions of this section by inspecting 
the various entries. The use of aprotic solvents improves nucleophilicity, especially of 
smaller anions, by eliminating hydrogen bonding.
6-9 Structure and SN2 Reactivity: The Substrate
Finally, does the structure of the alkyl portion of the substrate, particularly in the vicinity 
of the atom bearing the leaving group, affect the rate of nucleophilic attack? Once again, 
we can get a sense of comparative reactivities by looking at relative rates of reaction. Let 
us examine the kinetic data that have been obtained.
Branching at the reacting carbon decreases the rate 
of the SN2 reaction
What happens if we successively replace each of the hydrogens in a halomethane with a methyl 
group? Will this affect the rate of its SN2 reactions? In other words, what are the relative 
bimolecular nucleophilic reactivities of methyl, primary, secondary, and tertiary halides? Kinetic 
experiments show that reactivities decrease rapidly in the order shown in Table 6-8.
We can fi nd an explanation by comparing the transition states for these four substitu-
tions. Figure 6-8A shows this structure for the reaction of chloromethane with hydroxide 
ion. The carbon is surrounded by the incoming nucleophile, the outgoing leaving group, 
and three substituents (all hydrogen in this case). Although the presence of these fi ve groups 
increases the crowding about the carbon relative to that in the starting halomethane, the 
hydrogens do not give rise to serious steric interactions with the nucleophile because of 
their small size. However, replacement of one hydrogen by a methyl group, as in a halo-
ethane, creates substantial steric repulsion with the incoming nucleophile, thereby raising 
the transition-state energy (Figure 6-8B). This effect signifi cantly retards nucleophilic attack. 
If we continue to replace hydrogen atoms with methyl groups, we fi nd that steric hindrance 
to nucleophilic attack increases dramatically. The two methyl groups in the secondary sub-
strate severely shield the backside of the carbon attached to the leaving group; the rate of 
reaction diminishes considerably (Figure 6-8C and Table 6-8). Finally, in the tertiary sub-
strate, in which a third methyl group is present, access to the backside of the halide-bearing 
carbon is entirely blocked (Figure 6-8D); the transition state for SN2 substitution is energetically 
MODEL BUILDING
Table 6-8
Relative Rates of SN2 
Reaction of Branched 
Bromoalkanes with Iodide
Bromoalkane Rate
CH3Br 145
CH3CH2Br 1
CH3CHBr
CH3
A
 0.0078
CH3CBr
CH3
CH3
A
A
 NegligibleIn
cr
ea
si
ng
 s
iz
e 
o
f 
R
D
ec
re
as
in
g 
re
ac
tiv
ity
in
 S
N
2 
re
ac
tio
n
Figure 6-8 Transition states 
for SN2 reactions of hydroxide 
ion with
(A) chloromethane,
(B) chloroethane,
(C) 2-chloropropane, and
(D) 2-chloro-2-methylpropane.
H H
H
C
H
H H
TertiarySecondaryPrimaryMethyl
DCBA
O Cl O Cl O Cl O Cl
(No SN2 reaction; too much
steric hindrance)
(Slow reaction: hydrogens on
two methyl groups interfere)
\u2021\u2212 \u2021\u2212
Cl C
C
H H
\u2021\u2212
Cl
H H
H
\u2021\u2212
C
C
H
\u2021\u2212
ClHO HO HO HO
H3C
H H
H
\u2021\u2212
C
C
\u2021\u2212
Cl
H3C CH3
3157T_ch06_215-250.indd Page 240 4/18/09 7:53:41 AM user-s1723157T_ch06_215-250.indd Page 240 4/18/09 7:53:41 AM user-s172 /Users/user-s172/Desktop/Tempwork/Don'tDelete_Job/FREE036:Vollhardt/FREE036-/Users/user-s172/Desktop/Tempwork/Don'tDelete_Job/FREE036:V
Admin
Highlight
Admin
Highlight
Admin
Highlight
Admin
Rectangle
Admin
Rectangle
Admin
Highlight
Admin
Highlight
 C h a p t e r 6 241
inaccessible, and displacement of a tertiary haloalkane by this mechanism is not observed. To 
summarize, as we successively replace the hydrogens of a halomethane by methyl groups (or 
alkyl groups in general), SN2 reactivity decreases in the following order:
Relative SN2 Displacement Reactivity of Haloalkanes
Methyl . primary . secondary .. tertiary
 Fast Slower Very slow Not at all
Increasing SN2 reactivity
Exercise 6-27
Predict the relative rates of the SN2 reaction of cyanide with these pairs of substrates.
(a) 
Br Br CH3
and (b) CH3CH2CBr
CH3
CH3
CH3CH2CH2Brand
A
A
The Dilemma of Bromomethane: Highly Useful but Also Highly Toxic
Bromomethane, CH3Br, is a substance with numerous uses. 
Easy and inexpensive to prepare, it is employed as an insect 
fumigant for large storage spaces such as warehouses and 
railroad boxcars. It is also effective in eradicating insect 
infestations in soil and around several major crops, including 
potatoes and tomatoes. Not surprisingly, it owes part of its 
value to its high toxicity, which can be attributed largely to 
its SN2 reactivity. The chemistry of life is highly dependent 
on several classes of molecules containing nucleophilic 
groups such as amines ( \u2013 NH2 and related functions) and 
thiols ( \u2013 SH). The biochemical roles of these substituents 
are many and varied, as well as being critical to the survival 
of living organisms. Highly reactive electrophiles such as 
bromo methane wreak havoc on this biochemistry by indis-
criminately alkylating such nucleophilic atoms, that is, reacting 
through the SN2 mechanism to attach alkyl groups (in this 
case, a methyl group) to them (see, for example, the reaction 
below). Some of these processes can generate HBr as a by-
product, which amplifi es the danger posed by this material 
to living systems.
The toxicity of bromomethane is not limited to insects. 
Human exposure is known to cause numerous health prob-
lems: Direct contact causes burns to the skin; chronic 
 exposure leads to kidney, liver, and central nervous system 
damage; and inhalation of high concentrations can lead to 
the destruction of lung tissue, to pulmonary edema, and 
to death. The limit set for bromomethane exposure in the 
workplace is a concentration of 20 parts per million of 
 bromomethane vapor in ambient air. As is the case for so 
many substances that have been found to be useful in large-
scale applications in our society, bromomethane\u2019s toxicity 
poses a dilemma that requires the most responsible control of 
its use. The resolution between the issues of utility and safety 
does not always come easily, and the costs \u2014 human, envi-
ronmental, and economic \u2014 must be assessed most carefully.
\ufffdR CH3
CH3
BrHO OO R CH3 HBrSO O\ufffd \ufffdR S\ufffd HO O \ufffd
\ufffd
\ufffd
\ufffd
\ufffdS
A
Br \ufffd
Plant pathologist Frank Westerlund
Matheus
Matheus fez um comentário
tem respostas??
0 aprovações
Carregar mais