Impact of reaction products on the Grignard reaction with silanes and ketones

Article abstract of DOI:10.1016/j.jorganchem.2006.06.012

Grignard reactions with alkoxysilanes or carbonyl compounds produce alkoxymagnesium halides as by-products. Kinetic measurements for reactions of silanes and of a ketone were performed with Grignard reagents, enriched in alkoxymagnesium halides and taken in a great excess. The alkoxide-type reaction products complex tightly with Grignard reagents and enhance in this way their nucleophilicity, thus accelerating the reaction. However, alkoxides branched at α-C atom exert an unfavorable steric hindrance to reaction resulting in a decrease in the reaction rate.

Full text of DOI:10.1016/j.jorganchem.2006.06.012

Journal of Organometallic Chemistry 691 (2006) 4076–4079
www.elsevier.com/locate/jorganchem
Impact of reaction products on the Grignard reaction with silanes
and ketones
1
*
Dmitri Panov, Ants Tuulmets , Binh T. Nguyen
Institute of Organic and Bioorganic Chemistry, University of Tartu, Tartu 51014, Estonia
Received 21 February 2006; received in revised form 2 June 2006; accepted 9 June 2006
Available online 18 June 2006
Abstract
Grignard reactions with alkoxysilanes or carbonyl compounds produce alkoxymagnesium halides as by-products. Kinetic measure-
ments for reactions of silanes and of a ketone were performed with Grignard reagents, enriched in alkoxymagnesium halides and taken in
a great excess.
The alkoxide-type reaction products complex tightly with Grignard reagents and enhance in this way their nucleophilicity, thus accel-
erating the reaction. However, alkoxides branched at a-C atom exert an unfavorable steric hindrance to reaction resulting in a decrease in
the reaction rate.
ꢀ
2006 Published by Elsevier B.V.
Keywords: Grignard reaction; Ketones; Kinetics; Magnesiumalkoxides; Silanes
1
. Introduction
obtained at the expense of the ‘‘normal reaction’’, i.e., of
the Grignard addition. Additions of alkoxymagnesium
bromides or alkylmagnesium alkoxides imitating the reac-
tion products enhanced largely the relative yield of side
reactions, above all that of the reduction reaction. How-
ever, it has been noted [3] that the unbranched alkoholates
favored the addition reaction while a-branched alkoholates
gave rise to reduction of the ketone.
Based on their kinetic investigations Ashby et al. [4,10,11]
have shown that the product, alkoxymagnesium halide com-
plexes with the Grignard reagent tightly and the equilibrium
lies far toward the complex. The same proved to be valid for
alkylmagnesium alkoxides. The branched alkoxide ligands
derived from the Grignard addition to ketones caused a con-
siderable decrease in the reaction rate [4,10].
While the impact of alkoxides on the Grignard reaction
with silanes has been almost not investigated so far, also a
number of inconsistencies remain concerning the reaction
with ketones. Among others, relations between the addition
and reduction reactions require a further rationalization.
By reason of recent revival of our interest in the Grig-
nard reaction with silanes [12–14], we have addressed also
the role of the reaction products in the reaction. We found
Experiments with a great excess of a Grignard reagent
preclude the influence of reaction products. Under the pre-
parative conditions, with small or no excess of Grignard
reagent, the products accumulated during the reaction
can have a certain impact on the results.
Formerly we found that ethoxymagnesium chloride
increased the rate of the coupling reaction between ethyl-
magnesium chloride and ethyltriethoxysilane [1]. In con-
trast to this, some alkoxymagnesium bromides, e.g., the
reaction products, suppressed the rate of the Grignard
reaction with ketones [2–4]. In parallel to the kinetic
results, it has been signaled in numerous works [2,3,5–9]
that with ketones the relative amount of reduction
increases readily as the reaction proceeds. By the end of
the reaction a higher yield of reduction product was
*
Corresponding author.
E-mail addresses: dmitri.panov@ut.ee (D. Panov), ants.tuulmets@
ut.ee (A. Tuulmets).
1
Present address: Dow Corning Corporation. Midland, MI 48686-0995,
USA.
0
022-328X/$ - see front matter ꢀ 2006 Published by Elsevier B.V.
doi:10.1016/j.jorganchem.2006.06.012

D. Panov et al. / Journal of Organometallic Chemistry 691 (2006) 4076–4079
4077
that magnesium chloride from the coupling of organomag-
nesium chloride with chlorosilanes (Eq. (1)) had no effect
on the reaction. This was not the case for alkoxymagne-
sium chlorides from reactions with alkoxysilanes (Eq. (2)).
The products of the reaction with diisopropyl ketone
1
13
were identified by their H NMR, C NMR, and mass
spectra. Contribution of the enolization reaction was
negligible.
RMgCl þ MeSiCl ! MeRSiCl þ MgCl
ð1Þ
ð2Þ
3
2
2
3. Results and discussion
RMgCl þ SiðOEtÞ ! RSiðOEtÞ þ EtOMgCl
4
3
We involved our former kinetic results for the reaction
of ethyltriethoxysilane with ethylmagnesium chloride [1]
obtained by a thermographic method. As is seen from
Table 1, the limit rate constant is k = 0.036 s , indicat-
ing a rate enhancement
The experimental method of this work consisted in prep-
aration of Grignard reagents (n-butylmagnesium chloride
in diethyl ether) with variable content of alkoxymagnesium
chlorides and in determination of the rate constants and
products ratios for the reactions with silanes and with a
ketone. A great excess of modified Grignard reagent over
silanes and over the ketone was used to avoid possible con-
tribution of secondary reaction products. The alcohols
used for the production of the alkoxymagnesium moieties
in Grignard reagents were methanol, ethanol, isopropanol,
ꢀ1
1
Cl
EtMgCl + EtOMgCl
Et Mg
Mg Cl
ð3Þ
O
Et
by ethoxymagnesium chloride. Assuming a complete com-
plexation of the reagents according to [4,11], (Eq. (3)) the
rate constant can be calculated as
2
-butanol, and 2-methyl-2-butanol.
2
. Experimental
k
calc ¼ M
f
k
0
þ M
C
1
k ;
The experiments were carried out under dry argon in a
where M and M are the molar fractions of free and com-
f C
thermostated 100 mL double-necked round-bottom flask
equipped with a thermometer and a magnetic stirrer. The
n-BuMgCl/ROMgCl reagents were prepared adding calcu-
lated amounts of dry alkohols to n-butylmagnesium chloride
solution in diethyl ether. To start the reaction, calculated
amount of silane (providing a 10–20-fold excess of the Grig-
nard reagent) was injected into the flask. Samples were taken
by a syringe through the rubber septum and quenched with
ice-cold water (in case of the ethoxysilane) or with dry etha-
nol containing pyridine (in case of the chlorosilane thus pro-
viding ethoxysilanes). The organic layer was separated,
dried, and analyzed for ethoxysilanes by use of GLC.
The fast reactions were investigated in a thermostatic
flask equipped with a stirrer and a thermistor. The therm-
istor was connected through a bridge circuit to a recording
potentiometer. To a 15 mL sample of the Grignard reagent
was added 0.05 mL of ketone (providing a 20-fold excess of
the Grignard reagent), and the temperature change of the
reaction solution was recorded as a plot of temperature
vs. time. Use of a differential method for calculation of rate
constants [14] eliminated the contribution of heat exchange
with the reaction vessel.
plexed ethylmagnesium chloride, respectively. A good
accordance between the observed and calculated rate con-
stants (Table 1) proves the assumption of complete com-
plexation of the reagents. The nucleophilic ethoxy group
bound with the magnesium center evidently enhances the
nucleophilicity of the Grignard reagent thus accelerating
the reaction. This provides a more straightforward expla-
nation of the results than speculations presented in the pre-
vious paper [1].
A similar experiment with n-butylmagnesium chloride (a
GLC method) gave results (Fig. 1) supporting the conclu-
sions above.
Extension of the investigation to alkoxides other than
ethoxymagnesium chloride revealed a large contribution
of relatively fast replacement reactions at the silicon center
resulting in a set of competing and consecutive reactions
which made practically impossible to follow the kinetics
of the target reaction. However, from the initial periods
of the reactions with i-PrOMgCl/BuMgCl reagent, rate
constants were estimated. It appears that the effect of this
ligand is reverse to that of the ethoxy group (Fig. 1).
Check experiments using GLC indicated that the con-
secutive formation of triethylethoxysilane in kinetic mea-
surements of the reaction between ethylmagnesium
chloride reagents and ethyltriethoxysilane could be ignored
at least during first three half-lives used for calculation of
rate constants.
Table 1
ꢀ1
Pseudo-first order rate constants (s ) for the reaction of ethyltriethox-
ysilane (initial concentration 0.024 M) with ethylmagnesium chloride
(
3
1 M) in the presence of ethoxymagnesium chloride in diethyl ether at
0 ꢁC
EtOMgCl/EtMgCl
k
exp
k
calc
In reactions of tetraethoxysilane formation of dibutyl-
diethoxysilane was present, however, the reaction was
followed by consumption of the initial reagent
tetraethoxysilane with a great excess of the Grignard
reagent. Under these conditions kinetics of the reaction
obeyed the pseudo-first order law during five half-lives.
0
0
0
0.73
0
1
0.018
0.024
0.030
0.031
0.034
0.035
–
.30
.50
0.023
0.027
0.031
0.035
0.036
.98
.26

4078
D. Panov et al. / Journal of Organometallic Chemistry 691 (2006) 4076–4079
4
3
2
1
0
.5
4
The reaction with diisopropyl ketone implicates the
competing addition and reduction reactions. After working
up the reaction product mixture, the molar ratios of prod-
ucts, 2-methyl-3-isopropylheptane-3-ol (from the addition
reaction), and 2,4-dimethylpentane-3-ol (from the reduc-
tion reaction), respectively, were determined by GLC mea-
surements. The results are presented in Table 2 together
with relevant rate constants. Partial rate constants for com-
peting addition and reduction reactions were calculated
from the overall rate constants using the molar ratio of
the reaction products (second column in Table 1). It is seen
that alkoxy ligands not only affect the rate of the reaction
but also the ratio of the products. In the presence of meth-
oxymagnesium chloride both addition and reduction reac-
tions are accelerated while tert-pentoxymagnesium chloride
suppresses the rates of the reactions. The effect of the
ligands upon the addition reaction is considerably stronger
than for the reduction reaction. However, the effects are
similar with those obtained from the reactions with silanes.
Our experimental results lead to some general conclu-
sions. Grignard reagents, when the halogen is chlorine,
are predominantly dimeric in diethyl ether over a wide con-
centration range, particularly at the 0.5 M concentration
.5
3
.5
2
.5
1
.5
0
0
0.2
0.4
0.6
0.8
1
1.2
ROMgCl/BuMgCl
3
ꢀ1
Fig. 1. Pseudo-first order rate constants (k · 10 , s ) for the reaction of
n-butylmagnesium chloride (0.5 M) with tetraethoxysilane in the presence
of ethoxymagnesium chloride (r) or isopropoxymagnesium chloride at
20 ꢁC (j).
Similar complications were met when chlorosilanes were
introduced. Replacement of chlorine atoms by the alkoxy
group appeared to be competing with or even dominating
over the Grignard reaction under the conditions of our
experiment. However, qualitatively, it appeared to us that
the additions of methanol to the initial Grignard reagent
accelerated the reaction. To rationalize the matter, the
reaction with a ketone was subjected to the investigation.
Results of a kinetic investigation of the reaction between
n-butylmagnesium chloride in a great excess and diisopro-
pyl ketone are presented in Fig. 2. Methoxy- and ethoxy-
magnesium chlorides showed an accelerating effect while
isopropoxy- and other branched alkoxymagnesium chlo-
rides suppressed the reaction rate. These results are qualita-
tively the same as observed for the reaction with silanes.
[
11,15,16]. Therefore, the complexation with an alkoxy-
magnesium chloride involves a ligand replacement at the
magnesium atom (cf. Structures I and II).
Cl
Cl
R Mg
Mg
R
R Mg
Mg Cl
Cl
I
O
II R'
It is obvious that the donating ligand at the magnesium
atom, a solvent molecule or other, polarizes the C–Mg
bond, increasing the nucleophilicity of the C-atom. It is
also obvious that an increase in steric hindrance causes a
decrease in donating ability of the ligand regardless of its
Broensted basicity. In this context, the alkoxides should
0
0
0
0
0
0
0
0
0
0
0
0
.55
.50
.45
.40
.35
.30
.25
.20
.15
.10
.05
.00
ꢀ
ꢀ
ꢀ
arrange in the sequence RCH O > R CHO > R CO .
2
2
3
However, it should be noted that the branching at the
a-C atom actually operates in the b-position relative to
the Mg-center, thus reducing the steric requirements of
the ligand. As to the basicity/nucleophilicity of the alkox-
ides, the sequence arising from hydrogen-bond-donating
systems cannot be applied and probably the gas-phase
basicities should be considered [17] thus resulting in the
same sequence as above.
MeOMgCl
EtOMgCl
s-BuOMgCl
i-PrOMgCl
t-PentOMgCl
Table 2
a
Products ratios for the reaction of diisopropyl ketone with Grignard
reagents, and relevant rate constants
ꢀ1
Reagent
Red/add k (s
)
k
Add
k
Red
0
.00
0.25
0.50
0.75
1.00
1.25
1.50
0
0
0
.5 M BuMgCl/0.5 M MeOMgCl
.5 M BuMgCl
.5 M BuMgCl/0.5 M t-PentOMgCl 0.73
0.18
0.30
0.50
0.137
0.021
0.424 0.076
0.105 0.032
0.012 0.009
ROMgCl/n-BuMgCl
Fig. 2. Rate constants for the reaction of diisopropyl ketone with 0.5 M n-
BuMgCl in diethyl ether at 20 ꢁC vs. the relative content of alkoxymag-
nesium chloride in the reagent.
a
In product determinations 0.1 equiv. of the ketone relative to the
Grignard reagent was used.

D. Panov et al. / Journal of Organometallic Chemistry 691 (2006) 4076–4079
4079
At the same time all the alkoxides under consideration,
highly branched ones included, appear to complex almost
completely with the Grignard reagent thus being better
donors than the Cl-atom in the bridge position (cf struc-
tures I and II) and consequently should always accelerate
the reaction in comparison with the uncomplexed Grignard
reagent instead of suppressing the reaction rate. However,
in Table 2 the ordinary butylmagnesium chloride takes an
intermediate position between the alkoxy complexes as to
the reaction rate or to the reduction/addition ratio. It fol-
lows inevitably that the course of the reaction cannot be
determined exclusively by donating properties of the alkox-
ide ligands. On the contrary, their steric effects must be lar-
gely superimposed upon the reactivity.
to reactions resulting eventually in a decrease in the reac-
tion rate. As the Grignard addition reaction with ketones
is more susceptible to steric effects than the reduction, in
case of carbonyl compounds the ratio Red/Add increases
with an increase in steric requirements of alkoxides.
Acknowledgements
This work was financially supported by the Dow Corn-
ing Corporation (Midland, USA) and the Estonian Science
Foundation (Grant No. 6512).
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