Vollhardt  Capítulo 8 (Álcoois)
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Vollhardt Capítulo 8 (Álcoois)


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(a) CH3CH2CCH(CH3)2
O
B
 (b) 
H
CHO
 (c) CH3CH2 CH3
O
In Summary Reductions of aldehydes and ketones by hydride reagents constitute general 
syntheses of primary and secondary alcohols, respectively. The reverse reactions, oxidations 
of primary alcohols to aldehydes and secondary alcohols to ketones, are achieved with 
chromium(VI) reagents. Use of pyridinium chlorochromate (PCC) prevents overoxidation 
of primary alcohols to carboxylic acids.
8-7 Organometallic Reagents: Sources of Nucleophilic 
Carbon for Alcohol Synthesis
The reduction of aldehydes and ketones with hydride reagents is a useful way of synthesiz-
ing alcohols. This approach would be even more powerful if, instead of hydride, we could 
use a source of nucleophilic carbon. Attack by a carbon nucleophile on a carbonyl group 
would give an alcohol and simultaneously form a carbon \u2013 carbon bond. This kind of 
reaction \u2014 adding carbon atoms to a molecule \u2014 is of fundamental practical importance for 
synthesizing new compounds from simpler reactants.
To achieve such transformations, we need to fi nd a way of making carbon-based nucleo-
philes, R:2. This section describes how to reach this goal. Metals, particularly lithium and 
magnesium, act on haloalkanes to generate new compounds, called organometallic reagents, 
in which a carbon atom of an organic group is bound to a metal. These species are strong 
bases and good nucleophiles and as such are extremely useful in organic syntheses.
Alkyllithium and alkylmagnesium reagents are prepared 
from haloalkanes
Organometallic compounds of lithium and magnesium are most conveniently prepared by 
direct reaction of a haloalkane with the metal suspended in ethoxyethane (diethyl ether) or 
oxacyclopentane (tetrahydrofuran, THF). The reactivity of the haloalkanes increases in the 
order Cl , Br , I; the relatively unreactive fl uorides are not normally used as starting 
Sequence of events during the 
preparation of a Grignard reagent. 
From top to bottom: magnesium 
chips submerged in ether; begin-
ning of Grignard reagent forma-
tion, after addition of the organic 
halide; reaction mixture showing 
increasing dissolution of magne-
sium; the fi nal reagent solution, 
ready for further transformation.
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 C h a p t e r 8 305
materials in these reactions. Organomagnesium compounds, RMgX, are also called Grignard 
reagents, named after their discoverer, F. A. Victor Grignard.*
Alkyllithium Synthesis
 (CH3CH2)2O, 082108CCH3Br 1 2 Li uuuuuuuy CH3Li 1 LiBr
Methyl-
 lithium
HE
DG
Mg
HH3C
H3C
C
I
HE
DG
HH3C
H3C
C
MgI
THF, 20°C
\ufffd
1-Methylethyl-
magnesium iodide
Alkylmagnesium (Grignard) Synthesis
Alkyllithium compounds and Grignard reagents are rarely isolated; they are formed in 
solution and used immediately in the desired reaction. Sensitive to air and moisture, they 
must be prepared and handled under rigorously air- and water-free conditions. Simple 
examples, such as methyllithium, methylmagnesium bromide, butyllithium, and others, are 
commercially available.
The formulas RLi and RMgX oversimplify the true structures of these reagents. Thus, 
as written, the metal ions are highly electron defi cient. To make up the desired electron 
octet, they function as Lewis acids (Section 2-2) and attach themselves to the Lewis basic 
solvent molecules. For example, alkylmagnesium halides are stabilized by bonding to two 
ether molecules. The solvent is said to be coordinated to the metal. This coordination is 
rarely shown in equations, but it is crucial for the formation of the Grignard species.
OR X Mg\ufffd
Grignard Reagents Are Coordinated to Solvent
(CH )3CH O2 2 Mg\u2248
X
\ufffd
½
ý
k
O
)R
O
The alkylmetal bond is strongly polar
Alkyllithium and alkylmagnesium reagents have strongly polarized carbon \u2013 metal bonds; 
the strongly electropositive metal (Table 1-2) is the positive end of the dipole, as shown in 
the margin for CH3Li and CH3MgCl. The degree of polarization is sometimes referred to 
as \u201cpercentage of ionic bond character.\u201d The carbon \u2013 lithium bond, for example, has about 
40% ionic character and the carbon \u2013 magnesium bond 35%. Such systems react chemically 
as if they contained a negatively charged carbon. To symbolize this behavior, we can show 
the carbon \u2013 metal bond with a resonance form that places the full negative charge on the 
carbon atom: a carbanion. Carbanions, R2, are related to alkyl radicals, R. (Section 3-2), 
and carbocations, R1 (Section 7-5), by successive removal of one electron. Because of 
charge repulsion, the carbon in carbanions assumes sp3 hybridization and a tetrahedral 
structure (Exercise 1-16).
*Professor François Auguste Victor Grignard (1871 \u2013 1935), University of Lyon, France, Nobel Prize 1912 
(chemistry).
ANIM
ATION ANIMATED MECHANISM: 
 Formation of Grignard 
reagent from 1-bromobutane
REACTION
8 - 7 O r g a n o m e t a l l i c R e a g e n t s a n d A l c o h o l S y n t h e s i s
Methyllithium
Methylmagnesium
chloride
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306 C h a p t e r 8 H y d r o x y F u n c t i o n a l G r o u p : A l c o h o l s
A
A
OO MC
\ufffd\ufffd \ufffd\ufffd A
A
O M
Polarized Charge separated
Carbon\u2013Metal Bond
in Alkyllithium and Alkylmagnesium Compounds
C \ufffd \ufffd
M \ufffd metal
Carbanion
The preparation of alkylmetals from haloalkanes illustrates an important principle in 
synthetic organic chemistry: reverse polarization. In a haloalkane, the presence of the 
electronegative halogen turns the carbon into an electrophilic center. Upon treatment with 
a metal, the Cd1\u2013 Xd2 unit is converted into Cd2 \u2013 Md1. In other words, the direction of 
polarization is reversed. Reaction with a metal (metallation) has turned an electrophilic 
carbon into a nucleophilic center.
The alkyl group in alkylmetals is strongly basic
Carbanions are very strong bases. In fact, alkylmetals are much more basic than are amides 
or alkoxides, because carbon is considerably less electronegative than either nitrogen or 
oxygen (Table 1-2) and much less capable of supporting a negative charge. Recall (Table 2-2, 
Section 2-2) that alkanes are extremely weak acids: The pKa of methane is estimated to be 50. 
It is not surprising, therefore, that carbanions are such strong bases: They are, after all, the 
conjugate bases of alkanes. Their basicity makes organometallic reagents moisture sensitive 
and incompatible with OH or similarly acidic functional groups. Therefore, it is impossible 
to make organolithium or Grignard species from haloalcohols or halocarboxylic acids. On 
the other hand, such alkylmetals can be used as effi cient bases to turn alcohols into their 
corresponding alkoxides (see Section 8-3). The by-product is an alkane. The outcome of 
this transformation is predictable on purely electrostatic grounds.
Alkoxide Formation with Methyllithium
\ufffd\ufffd \ufffd\ufffd\ufffd\ufffd \ufffd\ufffd
H(CH3)3COO Li\ufffd(CH3)3CO\ufffdLi CH3O H CH3O\ufffd \ufffd
1,1-Dimethylethanol
(tert-Butylalcohol)
pKa \ufffd 18
Methyllithium Lithium tert-butoxide Methane
pKa \ufffd 50
Similarly, organometals hydrolyze with water \u2014 often violently \u2014 to produce a metal 
hydroxide and alkane.
Hydrolysis of an Organometallic Reagent
\ufffdCH3CH2CHCH2CH2MgBr HOH \ufffdCH3CH2CHCH2CH2H BrMgOH
100%
3-Methylpentylmagnesium
bromide
3-Methylpentane
A
CH3
A
CH3
The sequence Grignard (or alkyllithium) formation, also called metallation, followed by 
hydrolysis converts a haloalkane into an alkane. A more direct way of achieving the same 
goal is the reaction of a haloalkane with the powerful hydride donor lithium aluminum 
hydride, an SN2 displacement of halide by H
2. The less reactive NaBH4 is incapable of 
performing this substitution.
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