Vollhardt  Capítulo 6 (Haloalcanos)
36 pág.

Vollhardt Capítulo 6 (Haloalcanos)

Disciplina:Química Orgânica II963 materiais31.941 seguidores
Pré-visualização16 páginas
to our original expectation!

Increasing basicity

F2 , Cl2 , Br2 , I2

Increasing nucleophilicity in aprotic solvents

Increasing polarizability improves nucleophilic power
The solvation effects just described should be very pronounced only for charged nucleophiles.
Nevertheless, the degree of nucleophilicity increases down the periodic table, even for uncharged
nucleophiles, for which solvent effects should be much less strong, for example, H2Se . H2S .
H2O, and PH3 . NH3. Therefore, there must be an additional factor that comes into play.

This factor is the polarizability of the nucleophile (Section 6-1). Larger elements have
larger, more diffuse, and more polarizable electron clouds. These electron clouds allow for
more effective orbital overlap in the SN2 transition state (Figure 6-7). The result is a lower
transition-state energy and faster nucleophilic substitution.

Table 6-6

 Solvent

 Relative rate
Formula Name Classifi cation (krel)

CH3OH Methanol Protic 1

HCONH2 Formamide Protic 12.5

HCONHCH3 N-Methylformamide Protic 45.3

HCON(CH3)2 N,N-Dimethylformamide Aprotic 1,200,000

Relative Rates of SN2 Reactions of lodomethane with Chloride
Ion in Various Solvents
 Solvent
CH3I 1 Cl

2 uvy CH3Cl 1 I
2

 krel

Large 5p orbital, polarized toward
electrophilic carbon center

sp3 hybrid back lobe

Small 2p orbital,
relatively nonpolarized

X F

A B

−

I
δ+ δ−δ−δ+

−

C XC

Figure 6-7 Comparison of I2 and F2 in the SN2 reaction. (A) In protic solvents the larger iodide is a
better nucleophile, in part because its polarizable 5p orbital is distorted toward the electrophilic carbon
atom. (B) The tight, less polarizable 2p orbital on fl uoride does not interact as effectively with the
 electrophilic carbon at a point along the reaction coordinate comparable to the one for (A).

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

ANIM
ATION ANIMATED MECHANISM:

Nucleophilic substitution (SN2)

3157T_ch06_215-250.indd Page 237 5/6/09 5:53:58 PM user-s1723157T_ch06_215-250.indd Page 237 5/6/09 5:53:58 PM user-s172 /Users/user-s172/Desktop/Tempwork/Don'tDelete_Job/FREE036:Vollhardt/FREE036-06/Users/user-s172/Desktop/Tempwork/Don'tDelete_Job/FREE036:Vollhardt/FREE

Admin
Highlight

Admin
Highlight

238 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

Sterically hindered nucleophiles are poorer reagents
We have seen that the bulk of the surrounding solvent may adversely affect the power of
a nucleophile, another example of steric hindrance (Section 2-8). Such hindrance may also
be built into the nucleophile itself in the form of bulky substituents. The effect on the rate
of reaction can be seen in Experiment 7.

Experiment 7

CH3I CH3OCH3� �

A

A
CH3CO � CH3OCCH3

CH3

CH3

A

A

CH3

CH3

CH3O �

CH3I �

� I �

�� I �

Fast

Slower

Conclusion. Sterically bulky nucleophiles react more slowly.

Exercise 6-24

Which of the two nucleophiles in the following pairs will react more rapidly with bromomethane?

(a)
A

CH3S�
CH3

CH3CHS�or (b)
A

(CH3)2NH (CH3CH)2NH
CH3

or

Exercise 6-25

Working with the Concepts: Suggesting a Reaction Product by
Mechanistic Reasoning

Treatment of 4-chloro-1-butanol, :Cl
..

. . CH2CH2CH2CH2O
..

. . H, with NaOH in DMF solvent leads to
rapid formation of a compound with the molecular formula C4H8O. Propose a structure for this
product and suggest a mechanism for its formation.
Strategy
Rather than immediately trying to fi gure out the structure of the product of the reaction, it is often
more productive to “think mechanistically” and consider the reaction pathways available. If the
fi rst pathway doesn’t work, try to refi ne the problem — what is the change that takes place in the
molecule, and how could this change come about?
Solution
• The most obvious mechanism to try is an SN2 trajectory for the substrate and hydroxide:

HO � HOCH2CH2CH2CH2OHClCH2HOCH2CH2CH2 �� OO Cl �

Unfortunately, the product in this equation cannot be correct, because its molecular formula is
C4H10O2, not C4H8O.
• Let’s consider another approach. The substrate has the molecular formula C4H9OCl. Therefore,
the change in its conversion to C4H8O is loss of one hydrogen and the chlorine — that is, a mole-
cule of the strong acid HCl. How could we effect this change?
• Hydroxide is a base as well as a nucleophile; therefore, a reasonable alternative to the (incorrect)
SN2 reaction above is an acid-base reaction with the most acidic hydrogen in the substrate:

HO � H � OCH2CH2CH2CH2ClCH2Cl �� O H2OOCH2CH2CH2

MODEL BUILDING

Exercise 6-23

Which species is more nucleophilic: (a) CH3SH or CH3SeH; (b) (CH3)2NH or (CH3)2PH?

3157T_ch06_215-250.indd Page 238 4/18/09 7:53:25 AM user-s1723157T_ch06_215-250.indd Page 238 4/18/09 7:53:25 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
Callout
Nucleófilos

Admin
Highlight

 C h a p t e r 6 239

Nucleophilic substitutions may be reversible
The halide ions Cl2, Br2, and I2 are both good nucleophiles and good leaving groups.
Therefore, their SN2 reactions are reversible. For example, in acetone, the reactions between
lithium chloride and primary bromo- and iodoalkanes form an equilibrium that lies on the
side of the chloroalkane products:

CH3CH2CH2CH2I LiCl� CH3CH2CH2CH2Cl LiI�
Acetone

This result correlates with the relative stabilities of the product and starting material, which
favor the chloroalkane. However, this equilibrium may be driven in the reverse direction
by a simple “trick”: Whereas all of the lithium halides are soluble in acetone, solubility of
the sodium halides decreases dramatically in the order NaI . NaBr . NaCl, the last being
virtually insoluble in this solvent. Indeed, the reaction between NaI and a primary or sec-
ondary chloroalkane in acetone is completely driven to the side of the iodoalkane (the
reverse of the reaction just shown) by the precipitation of NaCl:

CH3CH2CH2CH2Cl NaI� CH3CH2CH2CH2I NaClg
Insoluble
in acetone

�
Acetone

The direction of the equilibrium in reaction 3 of Table 6-3 may be manipulated in
exactly the same way. However, when the nucleophile in an SN2 reaction is a strong base
(e.g., HO2 or CH3O

2; see Table 6-4), it will be incapable of acting as a leaving group. In
such cases, Keq will be very large and displacement will essentially be an irreversible process
(Table 6-3, reactions 1 and 2).

In Summary Nucleophilicity is controlled by a number of factors. Increased negative
charge and progression from right to left and down (protic solvent) or up (aprotic solvent)
the periodic table generally increase nucleophilic power. Table 6-7 compares the reactivity

Exercise 6-26

The formula of the organic product of this transformation is C4H8OCl
2, only a chloride ion away

from the correct product. How can we induce chloride ion to leave without adding any external
species? By displacement using the nucleophilic negatively charged oxygen at the opposite end
of the molecule, forming a ring:

�
 O ClCH2CH2CH2CH2 �OOO Cl �

CH2

CH2H2C

H2C

O

Indeed, such intramolecular SN2 reactions are widely used for the synthesis of cyclic compounds.
 You may ask why this reaction proceeds as it does. There are two main reasons. First, Brønsted-
Lowry acid-base reactions — proton transfers from one basic atom to another — are generally faster
than other processes. So removal of a proton from the hydroxy group of the substrate by hydrox-
ide ion (second equation) is faster than that same hydroxide displacing chloride in an SN2 process
(fi rst equation). Second, reactions that form fi ve- and six-membered rings are generally favored,
both kinetically and thermodynamically, over mechanistically analogous processes between two
separate molecules. Thus, the internal displacement of chloride by alkoxide in the last equation is
preferred over
Matheus Vitor fez um comentário
  • tem respostas??
    0 aprovações
    Carregar mais