Effect of solvent on the dimerization of the ansa-molybdocene catalyst [C2Me4Cp2Mo(OH)(OH2)][OTs]

Article abstract of DOI:10.1021/om8000907

The monomer-dimer equilibrium behavior of the [ansa-C₂Me ₄Cp₂Mo(OH)(OH₂)] [OTs] and [ansa-C ₂Me₄Cp₂Mo(μ-OH)]₂[OTs] ₂ complexes was explored in a variety of solvents. Only the monomer was detected spectroscopically in water, aqueous terahydrofuran, aqueous acetone, or aqueous dimethylsulfoxide, while appreciable dimerization was noted in aqueous solutions containing 50% ethanol or methanol. Several equilibrium constants (K_eq) were estimated. In water, K_eq ≥ 2 M at 25°C. In ethanol at 25°C, K_eq is on the order of 10 ^-2 M. In methanol at 25°C, K_eq ≈ 10^-6 M. The strong dependence of the monomer-dimer equilibrium on the solvent medium does not correlate with solvent polarity, hydrogen-bonding ability, or solvent basicity. These findings illustrate that catalyst dimerization can be suppressed more effectively by solvent choice than by electronic or steric modification of the Cp ligands. Because only the monomer is catalytically active, the effect of the monomer-dimer equilibrium on molybdocene-catalyzed nitrile hydration rates was investigated. Using 0.58 mM molybdocene in water, the rate of 3-hydroxypropionitrile hydration decreased in the order [Cp₂Mo(OH) (OH₂)] [OTs] > [ansa-C₂Me₄Cp ₂Mo(OH)(OH₂)][OTs] ～ [Cp′₂Mo(OH) (OH₂)][OTs] (Cp′ = η⁵-C₅H ₄Me). Using 2.8 mM molybdocene in water, the rate of 3-hydroxypropionitrile hydration catalyzed by [Cp₂Mo(OH)(OH ₂)I[OTs] is equal to that catalyzed by [Cp′₂Mo(OH) (OH₂)][OTs]. These trends demonstrate that (1) an effective method for increasing the rate of catalysis using Cp₂Mo(OH)(OH ₂)⁺ is to suppress its dimerization and (2) the effect of catalyst dimerization becomes more significant with increasing catalyst concentrations due to a concomitant increase in the percentage of [Cp ₂Mo(μ-OH)]₂²⁺ present in solution.

Full text of DOI:10.1021/om8000907

2608
Organometallics 2008, 27, 2608–2613
Effect of Solvent on the Dimerization of the ansa-Molybdocene
Catalyst [C2Me4Cp2Mo(OH)(OH2)][OTs]
Takiya J. Ahmed and David R. Tyler*
Department of Chemistry, UniVersity of Oregon, Eugene, Oregon 97403
ReceiVed January 31, 2008
The monomer-dimer equilibrium behavior of the [ansa-C2Me4Cp2Mo(OH)(OH2)][OTs] and [ansa-
C2Me4Cp2Mo(µ-OH)]2[OTs]2 complexes was explored in a variety of solvents. Only the monomer was
detected spectroscopically in water, aqueous terahydrofuran, aqueous acetone, or aqueous dimethylsul-
foxide, while appreciable dimerization was noted in aqueous solutions containing 50% ethanol or methanol.
Several equilibrium constants (Keq) were estimated. In water, Keq g 2 M at 25 °C. In ethanol at 25 °C,
Keq is on the order of 10-2 M. In methanol at 25 °C, Keq ≈ 10-6 M. The strong dependence of the
monomer-dimer equilibrium on the solvent medium does not correlate with solvent polarity, hydrogen-
bonding ability, or solvent basicity. These findings illustrate that catalyst dimerization can be suppressed
more effectively by solvent choice than by electronic or steric modification of the Cp ligands. Because
only the monomer is catalytically active, the effect of the monomer-dimer equilibrium on molybdocene-
catalyzed nitrile hydration rates was investigated. Using 0.58 mM molybdocene in water, the rate of
3-hydroxypropionitrile hydration decreased in the order [Cp2Mo(OH)(OH2)][OTs] > [ansa-C2Me4Cp2Mo-
(OH)(OH2)][OTs] ∼ [Cp′2Mo(OH)(OH2)][OTs] (Cp′ ) η5-C5H4Me). Using 2.8 mM molybdocene in water,
the rate of 3-hydroxypropionitrile hydration catalyzed by [Cp2Mo(OH)(OH2)][OTs] is equal to that
catalyzed by [Cp′2Mo(OH)(OH2)][OTs]. These trends demonstrate that (1) an effective method for
increasing the rate of catalysis using Cp2Mo(OH)(OH2)+ is to suppress its dimerization and (2) the effect
of catalyst dimerization becomes more significant with increasing catalyst concentrations due to a
2+
concomitant increase in the percentage of [Cp2Mo(µ-OH)]2 present in solution.
Introduction
The monomeric Cp′2Mo(OH)(OH2)+ (Cp′ ) C5H5 or C5H4-
Me) complexes are excellent Lewis acids that facilitate the
hydrolysis of coordinated nitriles and esters by intramolecular
nucleophilic attack of the hydroxo ligand (Figure 1).1–7 The rate
accelerations achieved for nitrile hydration and ester hydrolysis
reactions using the Cp(′)2Mo(OH)(OH2)+ complexes range from
modest to stellar (101-107 times). In an effort to increase the
practical utility of molybdocenes by modulating the electronics
of the catalyst, the catalytic activity of the ansa-molybdocene
C2Me4Cp2Mo(OH)(OH2)+ (1) was explored.1 The tetrameth-
ylethylene ansa-bridge did lead to an increase in the Lewis
acidity of the Mo center;8–10 however, the increased Lewis
acidity did not lead to faster reactivity. Specifically, the rate
Figure 1. Intramolecular attack of the hydroxo ligand on a substrate
coordinated to Cp(′)2Mo(OH)(OH2)+.
constants for ansa-C2Me4Cp2Mo(OH)(OH2)+-promoted nitrile
hydration, phosphate ester hydrolysis, and carboxylic ester
hydrolysis were shown to be 2-10 times smaller than the rate
constants obtained using the Cp2Mo(OH)(OH2)+ complex. This
result demonstrated that altering the electron density on the Mo
center oppositely affects the reactivity of the bound substrate
and the bound nucleophile. Although the catalytic activity of
the ansa-C2Me4Cp2Mo(OH)(OH2)+ complex was disappointing,
intriguing differences were noted in the synthesis and equilib-
rium behavior of the ansa-C2Me4Cp2Mo(OH)(OH2)+ and non-
ansa complexes.
* Corresponding author. E-mail: dtyler@uoregon.edu.
(1) Ahmed, T. J.; Zakharov, L. N.; Tyler, D. R. Organometallics 2007,
26, 5179–5187.
(2) Breno, K. L.; Ahmed, T. J.; Pluth, M. D.; Balzarek, C.; Tyler, D. R.
Coord. Chem. ReV. 2006, 250, 1141–1151.
Previous reports showed that the Cp(′)2Mo(OH)(OH2)+
species are in equilibrium with the hydroxo-bridged dimer
[Cp(′)2Mo(µ-OH)]22+, eg 1.1,11 When R ) H, Keq is (2.7 (
0.1) × 10-4 M in MOPS-buffered D2O (0.13 M, pD 6.8) at 25
°C. The addition of one methyl group to each Cp ring increased
the equilibrium constant by 2 orders of magnitude to (2.5 (
0.1) × 10-2 M. The large increase in Keq in the latter species
was attributed primarily to the decrease in the Lewis acidity of
the metal center of the Cp′Mo2+ unit (leading to weaker
(3) Breno, K. L.; Pluth, M. D.; Landorf, C. W.; Tyler, D. R. Organo-
metallics 2004, 23, 1738–1746.
(4) Breno, K. L.; Pluth, M. D.; Tyler, D. R. Organometallics 2003, 22,
1203–1211.
(5) Kuo, L. Y.; Barnes, L. A. Inorg. Chem. 1999, 38, 814–817.
(6) Kuo, L. Y.; Blum, A. P.; Sabat, M. Inorg. Chem. 2005, 44, 5537–
5541.
(7) Kuo, L. Y.; Perera, N. M. Inorg. Chem. 2000, 39, 2103–2106.
(8) Zachmanoglou, C. E.; Docrat, A.; Bridgewater, B. M.; Parkin, G.;
Brandow, C. G.; Bercaw, J. E.; Jardine, C. N.; Lyall, M.; Green, J. C.;
Keister, J. B. J. Am. Chem. Soc. 2002, 124, 9525–9546.
(9) Pons, V.; Conway, S. L. J.; Green, M. L. H.; Green, J. C.; Herbert,
B. J.; Heinekey, D. M. Inorg. Chem. 2004, 43, 3475–3483.
(10) Janak, K. E.; Shin, J. H.; Parkin, G. J. Am. Chem. Soc. 2004, 126,
13054–13070.
(11) Balzarek, C.; Weakley, T. J. R.; Kuo, L. Y.; Tyler, D. R.
Organometallics 2000, 19, 2927–2931.
10.1021/om8000907 CCC: $40.75
2008 American Chemical Society
Publication on Web 05/02/2008

Dimerization of an ansa-Molybdocene Catalyst
Organometallics, Vol. 27, No. 11, 2008 2609
pump-thaw cycles. All catalyst mixtures were prepared in J-Young
tubes or 9 in. NMR tubes that were subsequently flame-sealed
to prevent oxidation. The compounds [ansa-C2Me4Cp2Mo-
(OH)(OH2)][OTs],1 [C2Me4Cp2Mo(µ-OH)]2][OTs]2,1 [Cp′2Mo(µ-
15
OH)]2[OTs]2,14 and [Cp2Mo(µ-OH)]2[OTs]2 were prepared as
previously described. Nitrile hydration kinetics were modeled using
an iterative fitting program, GIT,16,17 and the following equations.
Mo-OH bonds in the dimeric structure) and to unfavorable
steric interactions between the Cp′ methyl substituents upon
dimerization. On the basis of the results obtained for the
Cp′2Mo(OH)(OH2)+ complex, we originally postulated that the
equilibrium for ansa-C2Me4Cp2Mo(OH)(OH2)+ would lie in
kapp
catalyst + nitrile
8 catalyst + amide
(2)
(3)
(4)
k2
2+
favor of the dimeric [C2Me4Cp2Mo(µ-OH)]2 species due to
catalyst + amide
9
8 catalyst + amide-d2
the fixed position of the rings and the increased Lewis acidity
2+
of the complex. Surprisingly, no [ansa-C2Me4Cp2Mo(µ-OH)]2
k3
was detected by 1H NMR spectroscopy in pure or buffered water
solutions of ansa-C2Me4Cp2Mo(OH)(OH2)+.1 This result was
puzzling because [ansa-C2Me4Cp2Mo(OH)(OH2)][OTs] crystal-
lizes as [ansa-C2Me4Cp2Mo(µ-OH)]2[OTs]2 from a supersatu-
rated solution in water.
catalyst + amide - d2
98 catalyst + amide
A representative GIT fit is shown in Figure 4. The apparent second-
order rate constants, kapp, obtained for nitrile hydration were used
to calculate rates and turnover frequencies. The rate constants
obtained for the H/D exchange of the R-hydrogens1 (k2 and k3) are
reported in the Supporting Information.
Investigation of Solvent Effects on the Behavior of C2Me4-
Cp2Mo(OH)(OH2)+. Crystalline [C2Me4Cp2Mo(µ-OH)]2]2+ (0.0045
g) was allowed to hydrolyze in D2O (1.50 mL) at 70 °C for 3 h.
Then 250 µL of deuterated acetone, methanol, ethanol, dimethyl
sulfoxide, or tetrahydrofuran was added to a 250 µL aliquot of the
hydrolyzed solution in a J-Young tube and mixed. The resulting
mixture was monitored by 1H NMR spectroscopy until it remained
unchanged for at least 10 h.
Nitrile Hydration. Stock solutions of C2Me4Cp2Mo(OH)(OH2)+,
Cp2Mo(OH)(OH2)+, and Cp′2Mo(OH)(OH2)+ were prepared by
dissolving the respective dimers in 0.13 M MOPS-buffered D2O.
The catalyst concentrations were confirmed using tetrabutylammo-
nium tetrafluoroborate as an internal standard. In an NMR tube, 7
µL of 3-hydroxypropionitrile was added to 0.500 mL of catalyst
solution. The tube was then heated to 80 °C for 14 days. Addition
of 3-HPN caused the stock solution of [Cp′2Mo(OH)(OH2)][OTs]
The extent of the monomer-dimer equilibrium has practical
consequences. For example, the tendency of molybdocenes to
dimerize may adversely affect the rates achieved by (CpR)2Mo-
(OH)(OH2)+-promoted reactions.12,13 As mentioned above,
although the Cp2Mo(OH)(OH2)+ complex appeared to be the
most reactive toward intramolecular nucleophilic attack, this
complex also has the greatest tendency to dimerize, giving rise
2+
to large amounts of the catalytically inactive [Cp2Mo(µ-OH)]2
.
1
to turn pink, while the other two solutions remained yellow. H
As a result, the rate of reaction per molybdenum center obtained
using the Cp2Mo(OH)(OH2)+ complex may actually be smaller
than that obtained for slightly less reactive molybdocene
complexes (i.e., ansa-C2Me4Cp2(OH)(OH2)+ and Cp′2Mo(OH)-
(OH2)+), which have a lesser tendency to dimerize. This result
suggests that suppressing catalyst dimerization may be a more
effective method of achieving faster rates than tuning the
electrophilicity of the metal center. Furthermore, if catalyst
dimerization does have a significant effect on the rate of
molybdocene-promoted reactions, it is expected to be most
significant in the molybdocene-catalyzed hydration of nitriles
where the difference in the rate constants for the variously
substituted molybdocenes is marginal.1
NMR spectroscopy (D2O) was used to monitor the disappearance
of 3-hydroxypropionitrile at 3.78 ppm (t, J ) 6.0 Hz, 2H,
HOCH2CH2CN) and 2.67 ppm (t, J ) 6.0 Hz, 2H, HOCH2CH2CN)
and the appearance of 3-hydroxypropionamide at 3.76 ppm (t, J )
6.0 Hz, 2H, HOCH2CH2CONH2) and 2.45 ppm (t, J ) 6.0 Hz,
2H, HOCH2CH2CONH2).
Results and Discussion
Investigation of the Equilibrium Behavior of ansa-C2-
Me4Cp2Mo(OH)(OH2)+. The ansa-C2Me4Cp2Mo(OH)(OH2)+
monomer exhibits hydrolytic behavior both similar to and
distinct from the non-ansa Cp(′)2Mo(OH)(OH2)+ monomers.
An important similarity is that the ansa-C2Me4Cp2Mo-
(OH)(OH2)+ monomer crystallizes as the ansa-[C2Me4Cp2Mo(µ-
In this paper, we explore the factors that control the
monomer-dimer equilibrium for ansa-C2Me4Cp2Mo(OH)-
(OH2)+. In addition, the consequences of dimer formation with
respect to the catalytic hydration activity of water-soluble
molybdocene complexes are discussed.
2+
OH)]22+ dimer. In addition, the ansa-[C2Me4Cp2Mo(µ-OH)]2
dimer dissolves in water to give the ansa-C2Me4Cp2Mo-
(OH)(OH2)+ monomer (Figure 2). This behavior is also
observed for the non-ansa complexes and is described by eq 1.
However, the behavior of the ansa-molybdocene differs from
that of the non-ansa complexes in two important ways. First,
Experimental Section
General Procedures. All experiments were performed under a
nitrogen atmosphere using standard glovebox techniques. Solvents
were prepared by purging with nitrogen or using three freeze-
(14) Balzarek, C.; Tyler, D. R. Angew. Chem., Int. Ed. 1999, 38, 2406–
2408.
(15) Ren, J. G.; Tomita, H.; Minato, M.; Osakada, K.; Ito, T. Chem.
Lett. 1994, 637–40.
(12) Hegg, E. L.; Mortimore, S. H.; Cheung, C. L.; Huyett, J. E.; Powell,
D. R.; Burstyn, J. N. Inorg. Chem. 1999, 38, 2961–2968.
(16) Stabler, R. N.; Chesick, J. P. Int. J. Chem. Kinet. 1978, 10, 461–9.
(17) Weigert, F. J. Comput. Chem. 1987, 11, 273–80.
(13) Deal, K. A.; Burstyn, J. N. Inorg. Chem. 1996, 35, 2792–8.

2610 Organometallics, Vol. 27, No. 11, 2008
Ahmed and Tyler
1
Figure 2. Stacked H NMR spectra showing the hydrolysis of [C2Me4Cp2Mo(µ-OH)]2[OTs]2 to [C2Me4Cp2Mo(µ-OH)]2[OTs]2 in D2O.
(From bottom to top: 0 h, 23 h, 84 h, 96 h, 108 h, and 168 h.) D ) [C2Me4Cp2Mo(µ-OH)]22+, M ) [C2Me4Cp2Mo(OH)(OH2)]+.
1
Figure 3. Aromatic region of H NMR spectra of ansa-C2Me4Cp2Mo(OH)(OH2)+ dissolved in 1:1 mixtures of (a) D2O/C2D5OD and (b)
D2O/CD3OD. D ) [ansa-C2Me4Cp2Mo(µ -OH)]22+, M ) [ansa-C2Me4Cp2Mo(OH)(OH2)]+, A ) [ansa-C2Me4Cp2Mo(OH)(X)]+ or [ansa-
C2Me4Cp2Mo(X)2], where X ) OC2D5 or OCD3.
the [Cp(′)2Mo(µ-OH)]22+ dimers dissolve readily in water, yet
species are in equilibrium; however, dehydration of [ansa-
C2Me4Cp2Mo(OH)(OH2)][OTs] upon crystallization to give
[ansa-C2Me4Cp2Mo(µ-OH)]2[OTs]2 cannot be ruled out. Dimer-
ization of ansa-C2Me4Cp2Mo(OH)(OH2)+ was observed in
2+
the ansa-[C2Me4Cp2Mo(µ-OH)]2
dimer is only sparingly
soluble in H2O (<1 mM). Furthermore, as shown in Figure 2,
the small amount of ansa-[C2Me4Cp2Mo(µ-OH)]22+ dimer that
does dissolve slowly hydrolyzes over hours to the ansa-
C2Me4Cp2Mo(OH)(OH2)+ monomer. Second, hydrolysis of the
ansa-dimerappearstoproceedtocompletion.No[C2Me4Cp2Mo(µ-
aqueous alcoholic solutions to give a mixture of the [ansa-
2+
C2Me4Cp2Mo(µ-OH)]2
dimer and the ansa-C2Me4Cp2-
Mo(OH)(OH2)+ monomer, which indicates that the monomer
and dimer are in equilibrium (eq 5), and the equilbrium has a
strong solvent dependence. This observation led us to further
investigate the behavior of the ansa-complexes in organic
solvent mixtures.
2+
1
OH)]2 is detectable in the aromatic region of the H NMR
spectrum once hydrolysis is complete at 25 °C or at elevated
temperatures.18
2+
Because [ansa-C2Me4Cp2Mo(µ-OH)]2 was not detectable
in solutions of the ansa-C2Me4Cp2Mo(OH)(OH2)+ monomer
in water, it was unclear whether the [ansa-C2Me4Cp2Mo(µ-
2+
OH)]2 and ansa-C2Me4Cp2Mo(OH)(OH2)+ species were in
an equilibrium analogous to eq 1. Crystallization of [ansa-
C2Me4Cp2Mo(µ-OH)]2[OTs]2 from supersaturated solutions of
[ansa-C2Me4Cp2Mo(OH)(OH2)][OTs] suggests that the two
(18) Note that the other spectroscopic handles in the [ansa-C2Me4Cp2Mo-
(µ-OH)]22+ species, namely, the methyl substituents on the bridging atoms,
could not be used to detect the dimer because they resonate at the same
frequency as in the ansa-C2Me4Cp2Mo(OH)(OH2)+ monomer in D2O.

Dimerization of an ansa-Molybdocene Catalyst
Organometallics, Vol. 27, No. 11, 2008 2611
To explore the behavior of the ansa-C2Me4Cp2Mo-
(OH)(OH2)+ complex in various solvent mixtures, aqueous
solutions containing only ansa-C2Me4Cp2Mo(OH)(OH2)+ (as
1
indicated by the H NMR spectra) were diluted with water-
miscible organic solvents. Addition of an equal volume of
methanol or ethanol to an aqueous solution of the monomeric
species resulted in a mixture of ansa-C2Me4Cp2Mo(OH)-
(OH2)+, [C2Me4Cp2Mo(µ-OH)]22+, and a third ansa-molyb-
docene species assigned to [ansa-C2Me4Cp2Mo(OH)(X)]+ or
[ansa-C2Me4Cp2Mo(X)2], where X ) OCD3 or OC2D5,
respectively (Figure 3). (The resonances for these latter
species, labeled A in Figure 3, have been observed before.1
Because the A resonances are always observed upon addition
of an alcohol to ansa-C2Me4Cp2Mo(OH)(OH2)+, assignment
to
the
[ansa-C2Me4Cp2Mo(OH)(X)]+
or
[ansa-
C2Me4Cp2Mo(X)2] species is logically suggested.1 Further-
Figure 4. Graph of concentration versus time and the GIT fit for
the ansa-C2Me4Cp2Mo(OH)(OH2)+-catalyzed hydration of 3-hy-
droxypropionitrile.
more, the alkoxide ligands may bridge the ansa-
C2Me4Cp2Mo2+ fragments, leading to the formation of [ansa-
2+
C2Me4Cp2Mo(µ-X)]2
instead of [ansa-C2Me4Cp2Mo(µ-
2+
OH)]2
or to an equilibrium mixture of both species.
termined by sterics or electronics. The ansa-linkage mini-
mizes, if not eliminates, steric interactions between the Cp
rings on different Mo centers. Moreover, the increased
electrophilicity of the ansa-C2Me4Cp2Mo2+ cation should
promote dimerization of the monomer. This statement is
based on the equilibrium data previously measured for the
non-ansa complexes, which showed more favorable dimer-
ization of the relatively electrophilic Cp complexes compared
with the Cp′ species due to a larger enthalpic gain achieved
Assignment of the dimeric species formed in aqueous alcohol
2+
as [ansa-C2Me4Cp2Mo(µ-OH)]2
instead of [ansa-
2+
C2Me4Cp2Mo(µ-X)]2 was based on excellent agreement
1
2+
with the H NMR spectrum of [C2Me4Cp2Mo(µ-OH)]2 in
pure water.) Note that, for the experiment depicted in Figure
3, 76% of the ansa-C2Me4Cp2Mo(OH)(OH2)+ monomer is
converted to the [ansa-C2Me4Cp2Mo(µ-OH)]22+ dimer in the
presence of methanol, while only 7% dimerized in the
solution containing aqueous ethanol. In contrast, no dimer
was observed on addition of an equal volume of THF, DMSO,
or acetone to an aqueous solution of ansa-C2Me4Cp2Mo(OH)-
2+
upon formation of the Mo-OH bonds in [Cp2Mo(µ-OH)]2
2+
compared to [Cp′2Mo(µ-OH)]2 (∆H° ) 6.2 ( 0.5 and 1.5
( 0.1 kcal/mol for Cp and Cp′, respectively, in eq 1). Because
the absence of dimerization noted for the ansa-
C2Me4Cp2Mo(OH)(OH2)+ monomer cannot be attributed to
the steric or electronic effects of the ligand, it is suggested
that the equilibrium established by the ansa-molybdocenes
is largely determined by the ability of the chosen medium to
solvate either the ansa-monomer or -dimer species. Effective
solvation of the ansa-dimer is likely dependent on the solvent
polarity, dielectric constant, hydrogen-bonding ability, and/
or solvent basicity; however, no correlation could be made
between the estimated Keq values and any one of these factors
(see Supporting Information).
2+
(OH2)+. In fact, crystals of [ansa-C2Me4Cp2Mo(µ-OH)]2
are immediately dissolved and completely hydrolyzed to the
monomer in slightly wet DMSO or THF, as shown by the
appearance of resonances at 7.0 and 6.2 ppm in the 1H NMR
spectra, which demonstrates that ansa-C2Me4Cp2Mo(OH)-
(OH2)+ is the preferred species in these wet solvents as well
as in water,; that is, the monomer is more stable than the
dimer in these solvents. Such stabilization of the monomeric
species is unprecedented using the non-ansa molybdocenes.
2+
Note that both non-ansa [Cp(′)2Mo(µ-OH)]2 dimers are
more stable than their respective Cp(′)2Mo(OH)(OH2)+
monomers (as indicated by the equilibrium constants, see the
Introduction) under all aqueous conditions examined thus
far.1,11 On the basis of the available spectroscopic data, as
well as the limit of detection for a 600 MHz NMR
spectrometer, Keq g 2 M for eq 5 in water (25 °C, pD 6.8),
which is 4 orders of magnitude greater than the Keq found
for [Cp2Mo(µ-OH)]22+. In contrast, Keq is approximately 9
× 10-2 and 7 × 10-6 M at 25 °C in ethanol and methanol,
respectively, based on the ratio of monomer to dimer present
in the 50% aqueous solutions previously discussed.19
The large differences in the estimated equilibrium constants
for eq 5 illustrate that the equilibrium established by the
tetramethylethylene-bridged ansa-molybdocenes is not de-
The strong solvent dependence of Keq in the ansa-complexes
is consistent with prior observations noted in the synthesis of
the ansa-C2Me4Cp2Mo(OH)(OH2)+ monomer.1 The Cp(′)2Mo-
(OH)(OH2)+ catalystsareaccessedbyhydrolysisofthe[Cp(′)2Mo-
2+
(µ-OH)]2 dimers, which are prepared by reaction of the
respective molybdocene dihydride with p-toluene sulfonic acid
in aqueous acetone (eq 6).14,15In contrast, reaction of the
(19) The Keq values in the aqueous methanol and ethanol solutions were
determined using an activity of 1 for H2O rather than using the molar
concentration of water. This was done to facilitate comparisons with the
Keq values for the non-ansa complexes obtained in dilute aqueous solution,
for which a value of 1 was used for the activity of water. If the molar
concentration of water is used instead of an activity of 1, then the Keq values
for the non-ansa complexes are (8.8 ( 0.3) × 10-8 and (8.1 ( 0.3) ×
10-6 M-1 for Cp and Cp′, respectively. Using the molar concentration of
water for the equilbrium constants measured for the ansa-bridged species,
Keq is at least 7 × 10-4 M-1 in dilute water and approximately 1 × 10-4
and 9 × 10-9 M-1 in aqueous ethanol and methanol, respectively.
analogous tetramethylethylene-bridged ansa-molybdocene di-
hydride with tosic acid did not give the [ansa-C2Me4Cp2Mo(µ-
OH)]2 dimer. Instead, the monomeric ansa-C2Me4Cp2Mo-
2+

2612 Organometallics, Vol. 27, No. 11, 2008
Ahmed and Tyler
Table 1. Comparison of Kinetic Data Obtained for the Hydration of
0.060 M 3-Hydroxypropionitrile at 80 °C Using a Total Mo
Concentration of 0.58 mM in 0.13 M MOPS-Buffered D2O
Table 2. Comparison of Kinetic Data Obtained for the Hydration of
0.26 M 3-Hydroxypropionitrile at 80 °C Using a Total Mo
Concentration of 2.8 mM in 0.13 M MOPS-Buffered D2O
TOF
TOF
[monomer]
(mM)
rate
(mol amide/mol
[monomer]
(mM)
rate
(mol amide/mol
ligand
(M s-1 × 108) monomer · s × 105)
ligand(s)
(M s-1 × 106)
monomer · s × 104)
{C2Me4(C5H4)2}
(C5H5)2
(C5H4Me)2
0.58
0.39
0.56
3.2 ( 0.2
3.9 ( 0.3
3.0 ( 0.2
5.6 ( 0.3
10 ( 1
5.4 ( 0.4
(C5H5)2
(C5H4Me)2
1.1
2.5
1.3 ( 0.1
1.3 ( 0.2
12 ( 1
5.3 ( 0.4
plex. Note that an equilibrium mixture of Cp2Mo(OH)(OH2)+
containing a 0.58 mM concentration of the Cp2Mo2+ unit
contains only 17% of the dimeric [Cp2Mo(µ-OH)]2 species
(OH)(OH2)+ species (eq 7) precipitates from this reaction
because, as this work has demonstrated, it is the thermodynami-
cally favored product in aqueous acetone.
2+
at 80 °C. To test whether dimerization affects the reaction rate
at higher concentrations of molybdocene, where the percentage
of dimer in solution is higher, a second comparison was made
using a total molybdenum concentration of 2.8 mM of the non-
ansa Cp′2Mo(OH)(OH2)+ and Cp2Mo(OH)(OH2)+ catalysts,
which contain approximately 6% [Cp′2Mo(µ-OH)2]22+ and 30%
[Cp2Mo(µ-OH)2]22+, respectively. The results are shown in
Table 2. Note that the rate of Cp′2Mo(OH)(OH2)+-catalyzed
HPN hydration is virtually identical to the rate obtained using
the Cp2Mo(OH)(OH2)+ catalyst when the concentrations of
catalyst and the associated dimer are increased. These data
indicate that a significant reduction in catalyst dimerization does
counterbalance the slight, yet significant, activity loss exhibited
by the Cp′2Mo(OH)(OH2)+ complex. It may be inferred by
comparison of this trend with that obtained at lower concentra-
tions of catalyst that the effect of dimerization will continue to
increase with increasing catalyst concentration.
A comparison of the turnover frequencies in Table 2 indicates
that the Cp2Mo(OH)(OH2)+ monomer is 2 times more reactive
than the Cp′2Mo(OH)(OH2)+ monomer toward the hydration
of 3-HPN. Data reported previously1 found that the rate
constants for these reactions are the same within error. The
discrepancy can be attributed to a difference in the concentration
of total molybdenum and substrate concentration for the two
Effect of Molybdocene Dimerization on the Rate of
Catalytic Nitrile Hydration. To investigate the impact of
catalyst dimerization on the rate of nitrile hydration, rates for the
Cp′2Mo(OH)(OH2)+- and Cp2Mo(OH)(OH2)+-catalyzed hydra-
tion of 3-hydroxypropionitrile (3-HPN) were compared to those
obtained with the ansa-C2Me4Cp2Mo(OH)(OH2)+ catalyst. The
experimental plan was for each reaction to be performed using
identical concentrations of nitrile and total Mo. Therefore, if
dimerization of the non-ansa molybdocenes has a significant
effect on the reaction rates, the rates will decrease with
increasing dimer formation in the order ansa-C2Me4-
Cp2Mo(OH)(OH2)+ > Cp′2Mo(OH)(OH2)+ > Cp2Mo(OH)-
(OH2)+ due to a decrease in the concentration of the active
monomer. (To summarize why this ordering is predicted: no
[ansa-C2Me4Cp2Mo(µ-OH)]22+ is observed in solutions of ansa-
C2Me4Cp2Mo(OH)(OH2)+ at any temperature. In the case of
the Cp′-containing molecule, the [Cp′2Mo(µ-OH)2]2+ dimer is
slightly more stable than Cp′2Mo(OH)(OH2)+ (eq 2, ∆Go )
2.2 kcal/mol at pH 7.2, 25 °C), and consequently only a small
amount of dimerization is observed in aqueous solution.
Appreciable catalyst dimerization is observed only for the
Cp2Mo(OH)(OH2)+ catalyst.) Because of the low solubility of
the ansa-C2Me4Cp2Mo(OH)(OH2)+ complex in water (<5 mM),
nitrile hydration was carried out using a total Mo concentration
of 0.58 mM in 0.13 M MOPS buffer. The resulting concentration
of monomer and the kinetic data for the three catalysts are
compared in Table 1. A sample kinetic trace and the calculated
sets of experiments, because both parameters affect kapp
.
Although the trends reported herein are slightly different, all
of the data show that Cp2Mo(OH)(OH2)+ is more reactive than
the Cp-substituted molybdocene complexes. In summary of this
section, the dimerization of molybdocene complexes does not
have an appreciable effect on the rate of nitrile hydration at
low catalyst concentration. However, at high concentrations, the
percentage of dimer present in solution becomes significant and
the net rate of hydration may be affected.
Summary
2+
The [Cp(′)2Mo(µ-OH)]2 dimers are more thermodynami-
cally stable than two Cp(′)2Mo(OH)(OH2)+ molecules (∆Go )
2.2 and 4.9 kcal/mol for Cp and Cp′, respectively, at 25 °C) in
water. A consequence of this dimer stability is that a significant
fraction of the catalytically active Cp′2Mo(OH)(OH2)+ monomer
is inactive because it is tied up in dimeric form. In contrast,
the experiments reported herein demonstrate that the mon-
omeric ansa-C2Me4Cp2Mo(OH)(OH2)+ complex is significantly
fit are shown in Figure 4. The second-order rate constants (kapp
)
for nitrile hydration and the first-order rate constants for H-D
exchange (k2 and k3) are found in the Supporting Information.
Comparison of the turnover frequencies in Table 1 shows
that Cp2Mo(OH)(OH2)+ is almost twice as reactive as the ansa-
C2Me4Cp2Mo(OH)(OH2)+ and Cp′2Mo(OH)(OH2)+ complexes.
However, because of the increased amount of dimer in solution
for the Cp2Mo(OH)(OH2)+ complex, the net reaction rate is
only 22% and 30% faster than the rates for the ansa-
C2Me4Cp2Mo(OH)(OH2)+ and Cp′2Mo(OH)(OH2)+ catalysts,
respectively. These data show that a small increase in reaction
rate can be achieved by suppressing catalyst dimerization using
the slightly less reactive ansa-C2Me4Cp2Mo(OH)(OH2)+ com-
2+
more stable than the [ansa-C2Me4Cp2Mo(µ-OH)]2 dimer in
water, as well as in aqueous mixtures of THF, DMSO, and
acetone. Experiments showed that the destabilization of ansa-
2+
[C2Me4Cp2Mo(µ-OH)]2 relative to the monomer is due to
solvation changes. Specifically, because the ansa-dimer crystal-
lizes from aqueous solution at low concentration, it is suggested
that in water the dimer is solvated more poorly than the
monomer. However, the ansa-dimer is soluble in DMSO and
THF, and it is unclear whether the energy of monomer or dimer

Dimerization of an ansa-Molybdocene Catalyst
Organometallics, Vol. 27, No. 11, 2008 2613
Supporting Information Available: All rate constants (kapp, k2,
and k3) obtained for catalysis experiments reported in Tables 1 and
2. A table of solvent properties (i.e., dielectric constants, pKa values,
etc.) for solvents used in this study. This material is available free
of charge via the Internet at http://pubs.acs.org.
is most affected by solvation in these solvents. Overall, these
results show that careful solvent selection is an effective method
of suppressing catalyst dimerization, which can lead to faster
rates of catalytic hydration.
Acknowledgment. We thank the NSF for funding through
NSF-CHE-0452004. T.J.A. would also like to acknowledge
a Haugland Fellowship for partial support.
OM8000907