P-S bond scission by bis(cyclopentadienyl)molybdenum(IV) dichloride, Cp2MoCl2(aq): First documented example of an organometallic complex hydrolyzing thiophosphinates

Article abstract of DOI:10.1021/ic050819j

Thiophosphinate hydrolysis involving P-S bond scission is desirable for the degradation of organophosphate neurotoxins, and we report the first case for such a hydrolytic process by an organometallic compound. The metallocene, bis(cyclopentadienyl)molybdenum(IV) dichloride, Cp₂MoCl₂ (Cp - η⁵-C₅H₅), hydrolyzes a variety of thioaryl diphenylphosphinates in an aqueous THF solution. P-S scission of p-methoxythiophenyl diphenylphosphinate has a 500-fold rate of acceleration in the presence of Cp₂MoCl₂(aq) with activation parameters of 20(3) kcal mol^-1 and -15(3) cal mol^-1 K^-1 for ΔH? and ΔS?, respectively. These activation parameters and the rate acceleration are consistent with an intermolecular hydrolytic process in which the Cp₂Mo serves as a Lewis acid to activate the phosphinate for nucleophilic attack. Furthermore, ρ = 2.3 (25°C) which indicates a single nonconcerted mechanism in which the rate determining step is the nucleophilic attack on the activated phosphinate.

Full text of DOI:10.1021/ic050819j

Inorg. Chem. 2005, 44, 5537−5541
P−S Bond Scission by Bis(cyclopentadienyl)molybdenum(IV) Dichloride,
Cp2MoCl2(aq): First Documented Example of an Organometallic
Complex Hydrolyzing Thiophosphinates
Louis Y. Kuo,*,† Angela P. Blum,† and Michal Sabat‡
Department of Chemistry, Lewis & Clark College, Portland, Oregon 97219, and the Department
of Chemistry, UniVersity of Virginia, CharlottesVille, Virginia 22904
Received May 20, 2005
Thiophosphinate hydrolysis involving P−S bond scission is desirable for the degradation of organophosphate
neurotoxins, and we report the first case for such a hydrolytic process by an organometallic compound. The
metallocene, bis(cyclopentadienyl)molybdenum(IV) dichloride, Cp2MoCl2 (Cp ) η5-C5H5), hydrolyzes a variety of
thioaryl diphenylphosphinates in an aqueous THF solution. P
−
S scission of p-methoxythiophenyl diphenylphosphinate
1
has a 500-fold rate of acceleration in the presence of Cp2MoCl2(aq) with activation parameters of 20(3) kcal mol-
1
1
and
are consistent with an intermolecular hydrolytic process in which the Cp2Mo serves as a Lewis acid to activate the
phosphinate for nucleophilic attack. Furthermore, F ) 2.3 (25 C) which indicates a single nonconcerted mechanism
in which the rate determining step is the nucleophilic attack on the activated phosphinate.
− ∆ ∆
15(3) cal mol- K- for H‡ and S‡, respectively. These activation parameters and the rate acceleration
°
Introduction
necessitates the use of model compounds such as phosphi-
nates [R2P(O)‚OR′], thiophosphinates [R2P(O)‚SR′], phospho-
nothioate [RP(O)‚(OR′)SR′′], and thiophosphate esters [R2P-
(S)‚OR′]. In studies with model compounds, oxone8 and
micellar iodoso- and iodoxybenzoates9 degraded organo-
phosphorus molecules, and selective P-S fission was seen
for phosphonothioate degradation.
We report the first case of thiophosphinate hydrolysis by
an organometallic compound, which may open up a new
class of reagents for the degradation of organophosphorus
neurotoxins. The metallocene bis(cyclopentadienyl)molyb-
denum(IV) dichloride10 (Cp2MoCl2: Cp ) η5-C5H5) was
chosen because of its water solubility and aqueous proper-
ties.11 Structurally, Cp2MoCl2 resembles a clamshell where
The degradation of organophosphate toxins is a national
security goal because of the threat of chemical warfare agents
and the 1997 Chemical Weapons Convention treaty.1 Nerve
agents such as fluorophosphonates are readily hydrolyzed
in alkaline solution through P-F cleavage, whereas P-S
bond cleavage for nerve agents such as VX is more difficult.2
Alkaline hydrolysis of VX in 0.1 M aqueous NaOH results
in both P-S (87%) and P-O (13%) cleavage.3 However,
P-O cleavage yields a phosphonothioate ion that is nearly
as toxic as the parent VX molecule.4 Therefore, there is a
major incentive to find reactions that cleave the P-S bond
of phosphonothioates through perhydrolytic5,6 and aqueous7
pathways. The high toxicity of organophosphorus neurotoxins
* To whom correspondence should be addressed. E-mail: kuo@lclark.edu.
† Lewis & Clark College.
(6) (a) Yang, Y.-C.; Szafraniec, L. L.; Beaudry, W. T.; Bunton, C. A. J.
Org. Chem. 1993, 58, 6964. (b) Yang, Y.-C.; Berg, F. J.; Szafreniec,
L. L.; Beaudry, W. T.; Bunton, C. A.; Kumar, A. J. Chem. Soc. Perkin
Trans. 1997, 2, 607.
(7) Yang, Y.-C.; Szafraniec, L. L.; Beaudry, W. T.; Rohrbaugh, D. K.;
Procell, L. R.; Samuel, J. B. J. Org. Chem. 1996, 61, 8407.
(8) Blasko, A.; Bunton, C. A.; Kumar, A. J. Phys. Org. Chem. 1997, 10,
427.
(9) (a) Moss, R. A.; Morales-Rojas, H.; Zhang, H.; Park, B. D. Langmuir
1999, 15, 2738. (b) Blasko, A.; Bunton, C. A.; Hong, Y. S.; Mhala,
M. M.; Moffatt, J. R.; Wright, S. J. Phys. Org. Chem. 1991, 4, 618.
(c) Moss, R. A.; Ragunathan, K. G. Langmuir 1999, 15, 107.
(10) Cooper, R. L.; Green, M. L. H. J. Chem. Soc. A 1967, 1155.
(11) Kuo, L. Y.; Sabat, M.; Kanatzidis, M. G.; Tipton, A. L.; Marks, T. J.
J. Am. Chem. Soc. 1991, 113, 9027.
‡ University of Virginia.
(1) Conference on Disarmament. The Convention on the Prohibition of
the Development, Production, Stockpiling and Use of Chemical
Weapons on Their Destruction; Geneva, August 1992, CD/1170.
(2) Yang, Y.-C. Acc. Chem. Res. 1999, 32, 109.
(3) Yang, Y.-C.; Baker, J. A.; Ward, J. R. Chem. ReV. 1992, 92, 1729.
(4) (a) Epstein, J.; Callahan, J. J.; Bauer, V. E. Phosphorus 1974, 4, 157.
(b) Yang, Y.-C.; Szafraniec, L. L.; Beaudry, W. T.; Rohrbaugh, D.
K. J. Am. Chem. Soc. 1990, 112, 6621.
(5) (a) Kennedy, R. J.; Stock, A. M. J. Org. Chem. 1960, 25, 1901. (b)
Zhu, W.; Ford, W. T. J. Org. Chem. 1991, 56, 7022. (c) Webb, K. S.
Tetrahedron Lett. 1994, 35, 3457. (d) Bunton, C. A.; Foroudian, H.
J.; Kumar, A. J. Chem. Soc. Perkin Trans. 1995, 2, 33.
10.1021/ic050819j CCC: $30.25
Published on Web 06/24/2005
© 2005 American Chemical Society
Inorganic Chemistry, Vol. 44, No. 15, 2005 5537

Kuo et al.
Figure 1. 31P NMR stacked plot of the hydrolysis of I by Cp2MoCl2., monitoring the P-S scission of I (4 mM) by Cp2MoCl2 (33 mM) in a D2O/THF (1:2)
solution at 30 °C with 41 mM MOPS at pH 5.0. Each spectrum is separated by a seven minute time interval. The asterisked signal at 41.9 ppm (*) is the
starting material (I), while the signal at 21.0 ppm (b) is the diphenylphosphoric acid product. A trace signal at 38.5 (9) is attributable to an adduct formed
between Cp2MoCl2 and diphenylphosphoric acid.
and used without further purification. The thioaryl diphenylphos-
phinates were prepared according to the procedure of Blasko and
co-workers.8 Manipulations with Cp2MoCl2 were done in an
Innovative Technology System One Glovebox or with standard
Schlenk techniques. All solvents used in the hydrolysis studies were
purged with N2 for >10 min, and the reported pH readings in D2O
are uncorrected. Stock solutions of Cp2MoCl2 in D2O containing
41 mM MOPS were made and adjusted to pH 4.5 with concentrated
HCl or NaOH prior to kinetic measurements. The hydrolysis
reactions, which were followed by 31P NMR, were initiated by
adding a degassed THF solution of the thioaryl diphenylphosphinate
to the aqueous Cp2MoCl2 so that their final concentrations were 4
and 33 mM, respectively.
After it sat for more than a week, the reaction of Cp2MoCl2 with
p-methoxythiophenyl diphenylphosphinate (I) in the NMR tube
yielded yellow needles that were washed with a 1:1 ether/hexane
mixture. The compound Cp2Mo(S-C6H4-OCH3)2 crystallizes in the
monoclinic space group C2/c with a ) 21.983(2) Å, b ) 6.8325-
(5) Å, c ) 13.883(1) Å, â ) 96.509(2)°, and Z ) 4 at 153(2) K.
Data collection was done on a Bruker SMART APEX CCD
diffractometer with 13991 reflections (crystal size ) 0.27 × 0.22
× 0.18 mm). The structure was solved by direct methods with the
SHELXTL package (Sheldrick, G. M. SHELXTL-97, version 5.10;
Bruker AXS, Madison, WI 53719). The final refinement converged
to R ) 4.13%. Further details on the crystallographic collection
are included in the Supporting Information material.
both cyclopentadienyl ligands flank a pseudotetrahedral Mo-
(IV) coordinated to two chlorides.12 In water, the cyclopen-
tadienyl rings remain bound to the tetrahedral Mo(IV) center
even at neutral pH. Meanwhile, both chlorides rapidly
hydrolyze off (τ1/2 ≈ 20 min) to form aquated species with
pKa values at 5.5 and 8.5.11 These aqueous properties and
the diamagnetic d2 molybdenum center make this metal-
locene amenable for observing phosphinate hydrolysis with
NMR methods.
The Cp2MoCl2(aq) complex has been found to hydrolyze
activated13 and inactivated14 phosphate esters with rate
accelerations of 107 to 108. It was postulated that the
mechanism proceeds through intramolecular attack on the
phosphate by a Cp2Mo-bound hydroxide. We also showed
that the same metallocene hydrolyzes the thiophosphate ester
parathion through nucleophilic attack by a water solvent
molecule at the R carbon of the ethyl group.15 The Cp2Mo
center serves as a coordinating Lewis acid that activates the
thiophosphate for this intermolecular process with up to a
103 rate acceleration. Herein, we extend the well-known Cp2-
Mo16 coordination chemistry toward aqueous P-S scission
transformation for the long-term goal of determining which
factors promote phosphonothioate hydrolysis.
Materials and Methods
Results and Discussion
1
31P and H NMR spectra were obtained on a Bruker Avance-
We set out to see if the molybdocene complex could
promote P-S cleavage of thiophosphinates, such as I, to
yield diphenylphosphonic acid and p-methoxythiophenol.
The addition of THF to buffered (pH 4.5) aqueous solutions
of Cp2MoCl2 (33 mM) solubilized the diphenylarylthiophos-
phinate (4 mM), which was monitored with 31P NMR
spectroscopy. Figure 1 clearly shows the disappearance of
the starting thiophosphinate (41.8 ppm) and the appearance
of a new upfield peak at 21.0 ppm that was diphenylphos-
phonic acid as identified through authentic addition. In
addition, a signal at 38.5 ppm is seen in trace amounts which
increases when we add a 1:1 adduct of diphenylphosphonic
acid and Cp2MoCl2(aq).
300 at 121 and 300 MHz, respectively, and the phosphorus spectra
were acquired using inverse-gated decoupling with a delay of ∼4
T1. The Cp2MoCl2 compound was obtained from Strem Chemical
Co. (Newburyport, MA), and all reagents for the synthesis of the
thiol phosphinates were purchased from Aldrich (Milwaukee, WI)
(12) Prout, C. K.; Cameron, T. S.; Forder, R. A.; Critchley, S. R.; Denton,
B.; Rees, G. V. Acta Crystallogr. 1974, B30, 2290.
(13) Kuo, L. Y.; Kuhn, S. Inorg. Chem. 1995, 34, 5341.
(14) Kuo, L. Y.; Barnes, L. A. Inorg. Chem. 1999, 38, 814.
(15) Kuo, L. Y.; Perera, N. Inorg. Chem. 2000, 39, 2103.
(16) (a) Gore, E.; Green, M. L. H.; Harriss, M. G.; Lindsell, W. E.; Shaw,
H. J. Chem. Soc. A 1969, 1981. (b) Harriss, M. G.; Green, M. L. H.;
Lindsell J. Chem. Soc. A 1969, 1453. (c) Green, M. L. H.; Lindsell,
W. E. J. Chem. Soc. A 1967, 1455.
5538 Inorganic Chemistry, Vol. 44, No. 15, 2005

Organometallic Complex Hydrolyzing Thiophosphinates
Figure 2. Crystal structure of Cp2Mo(S-C6H4-pOCH3)2 (II). Thermal
ellipsoids represent 30% probabilities. Crystals were formed from the
reaction of I with Cp2MoCl2 that was left in the NMR tube to settle for
more than a week. Major geometrical parameters of II are as follows: Mo-
S1 ) 2.4775(6) Å, average Mo-C ) 2.32(5) Å, and S-Mo-S ) 77.72-
(3)°.
Therefore, both peaks, at 21.0 and 38.5 ppm, indicate the
appearance of diphenylphosphonic acid as one of the prod-
ucts in the reaction of I with Cp2MoCl2. As was the case
with phosphate triester hydrolysis (parathion and paraoxon)
by Cp2MoCl2(aq),15 we were unable to unequivocally es-
tablish from NMR alone the presence of a putative Cp2Mo-
phosphinate intermediate. The other major product is p-meth-
oxythiophenol, which was confirmed (1H NMR) with authen-
tic addition to the final product mixture. The net reaction
for this process at pH 4.5 can then be summarized with eq 1.
Figure 3. Arrhenius plot of the hydrolysis of I by Cp2MoCl2. Activation
energy parameters were measured as ∆H‡ ) 20(3) kcal/mol and ∆S‡
)
15(3) eu in the conditions described in the Experimental Section.
similar phenyl orientation relative to the metallocene equato-
rial plane in a Cp2Mo(NH3)(SC6H5)+ structure in which
extended HMO and steric energy calculations were used to
account for the thiophenyl geometry.21
The disappearance of I followed first-order kinetics with
a rate constant of 0.30 h-1 (50 °C) at pH 4.5. When the
identical reaction was carried out in the absence of Cp2-
MoCl2, the rate constant was 6.0 × 10-4 h-1, which
represents a 500-fold rate acceleration with the molybdocene
compound. The reaction was first order in I, and solubility
issues in an aqueous THF solution precluded the determi-
nation of the reaction order of the Cp2MoCl2(aq) concentra-
tion. The rates of hydrolysis by Cp2MoCl2 reach a maximum
at pH 6 and then drop in the alkaline range. It is interesting
to note that this rate acceleration is close to the ∼103 rate
acceleration observed when the phosphate triester, parathion,
is hydrolyzed by Cp2MoCl2(aq).15
The well-behaved kinetics of thiophosphinate hydrolysis
prompted us to look at its temperature and leaving group
dependencies to gain insight into the transition state for this
process. The Arrhenius plot (Figure 3) of the hydrolysis of
I by Cp2MoCl2 gives a ∆S‡ value of -15(3) eu in the 20-
60 °C temperature range, indicative of an ordered transition
state consistent with an intermolecular process.
Prior measurements of alkylthiol dialkylphosphinate hy-
drolysis in alkaline solution yielded a ∆S‡ value of -41 to
-49 eu.22 The higher ∆S‡ value for the Cp2Mo-promoted
process is consistent with the notion that the cyclopentadienyl
ligand provides a more disordered transition state (i.e., free
rotation about the centroid-Mo bond) than a simple hy-
droxide attack on the thiophosphinate functionality. This
implies that coordination of the Cp2Mo fragment to the
phosphinate is part of the transition state.
The thiophenol product in eq 1 coordinates to Cp2Mo and
precipitates nicely in the NMR tube to form X-ray quality
crystals of a bis(p-methoxythiophenol) adduct (II). X-ray
diffraction reveals that single crystals of II are composed of
well-separated and discrete Cp2Mo(S-C6H4-pOCH3)2 mol-
ecules in which the Mo(IV) ion adopts the familiar “clam-
shell” geometry found in other Cp2MoLn complexes.17 This
geometry is unexceptional with regard to the average Mo-C
bond distance (2.32(5) Å), and the Mo-S distance (2.4775-
(6) Å) is similar to that of other Cp2Mo derivatives containing
S-bonded ligands.18 Even the S-Mo-S angle of 77.72(3)°
is within the predicted L-M-L angle of ∼78° calculated
for bent d2 Cp2ML2 complexes.19 The orientation of the two
phenyl rings lie almost in the S-Mo-S plane (Figure 2)
with a dihedral angle of 38.4°, which is consistent with the
crystal structure of the Cp2Ti(SPh)2 complex in which the
two phenyl rings point in almost opposite directions with
one ring above and the other below the S-Ti-S plane.20
Furthermore, Calhorda and co-workers have also seen a
(17) (a) Calhorda, M. J.; de C. T. Carrondo, M. A. A. F.; De Costa, R. G.;
Dias, A. R.; Duarte, M. T. L. S.; Hursthouse, M. B. J. Organomet.
Chem. 1987, 320, 53. (b) Silavwe, N. D.; Chiang, M. Y.; Tyler, D. R.
Inorg. Chem. 1985, 24, 4219. (c) Prout, C. K.; Critchley, S. R.;
Cannillo, E.; Tazzoli, V. Acta Crystallogr. 1977 B33, 456. (d) Prout,
C. K.; Couldwell, M. D.; Forder, R. A. Acta Crystallogr. 1977, B33,
218. (e) Prout, C. K.; Allison, G. B.; Delbaere, L. T. J.; Gore, E. S.
Acta Crystallogr. 1972, B28, 3043.
(18) (a) de C. T. Carrondo, M. A. A. F.; Matias, P. M.; Jeffrey, G. A. Acta
Crystallogr. 1984, C40, 932. (b) Block, H. D.; Allman, R. Cryst. Struct.
Commun. 1975, 4, 53. (c) Knox, J. R.; Prout, C. K. Acta Crystallogr.
1969, B25, 2013. (d) Kutoglu, A.; Kopf, H. J. Organomet. Chem. 1970,
25, 455. (e) Knox, J. R.; Prout, C. K. Acta Crystallogr. 1969, B25,
2482.
In previous studies of Cp2MoCl2-promoted hydrolysis of
activated phosphate diesters, the ∆S‡ was measured to be
(21) Calhorda, M. J.; de C. T. Carrondo, M. A. A. F.; Garcia, M. H.;
Hursthouse, M. B. J. Organomet. Chem. 1988, 342, 209.
(22) Cook, R. D.; Farah, A.; Ghawi, L.; Itani, A.; Rahil, Can. J. Chem.
1986, 67, 1630.
(19) Lauher, J. W.; Hoffman, R. J. Am. Chem. Soc. 1976, 98, 1729.
(20) Muller, E. G.; Watkins, S. F.; Dahl, L. J. Organomet. Chem. 1976,
111, 73.
Inorganic Chemistry, Vol. 44, No. 15, 2005 5539

Kuo et al.
Scheme 1
0.0 eu,13 which was attributable to an intramolecular process.
Moreover, phosphate hydrolysis reactions promoted by metal
complexes have yielded rate accelerations of >107 and 102
for intramolecular and intermolecular processes, respec-
tively.23 The 102 rate acceleration and the negative ∆S‡ for
the Cp2MoCl2-promoted hydrolysis of I is consistent with a
bimolecular process in which the Cp2Mo serves to activate
the thiol phosphinate for nucleophilic attack. Molecular
orbital calculations have suggested that the PdO group exists
primarily in the dipolar form with a highly negative charge
on the phosphinyl oxygen atom.24 Coordination of the Cp2-
Mo2+ group to the phosphinyl oxygen would increase the
electrophilicity at the phosphorus atom for nucleophilic
attack.
Figure 4. Linear free-energy relationship of thiophophosphinate hydrolysis
by Cp2MoCl2. Hydrolysis reactions were carried out at 20 °C under the
conditions described in the Experimental Section. The F value was measured
to be 2.3.
The thiophenolate leaving group prompted us to make
several aryl derivatives of I at the para position which would
allow us to probe the sensitivity of the P-S scission toward
electronic effects as well as reveal possible mechanistic
pathways. A number of hydrolysis studies have already been
done with thioaryl phosphinates22,25 and aryl phosphinates.26
A mechanism involving direct displacement (SN2(P)) results
in a large rate difference between the phosphinate and
thiophosphinate hydrolysis, and the rates themselves would
correlate with Hammett’s σ-. Alternatively, in a reaction that
goes through an intermediate, the rate determining step for
both substrates would be the formation of the intermediate
(Scheme 1) because the leaving groups are less basic than
hydroxide. This leads to a relatively small difference in the
rates of thiophosphinates and phosphinates, and the rates of
hydrolysis correlate with the Hammett’s σ constants.25
In Figure 4, there is linear free energy relationship between
the Hammett’s σ constant for the substituent on the leaving
group and the rate of hydrolysis.
Scheme 2
with σ constants.25,26 Thiophosphinate hydrolysis studies by
hydroxide give a F (25 °C) value of 1.46.25 Cook and co-
workers have listed an array of F values (25 °C) for the
alkaline hydrolysis of phosphinates and thiol phosphinates
in various solvents (no metal ions), and the highest value
recorded is 2.2 for a phosphinate.25 The measured F in thiol
phosphinate hydrolysis by Cp2MoCl2 has a value of 2.3 (25
°C) in Figure 4. This indicates that, in the organometallic
system, the hydrolytic process is more sensitive to electronic
effects, which may result from the unique role of the metal
in promoting the P-S fission process.
Dunn and Buncel have proposed a mechanism for the
metal ion-catalyzed nucleophilic displacement of p-nitro-
phenyl diphenylphosphinate by ethoxide, which resembles
the intermediate pathway depicted in Scheme 2 (R )
4-nitrobenzene, X ) O, and nucleophile ) ethoxide).27 In
their proposal, monovalent metal ions (K+, Na+, and Li+)
serve two roles, association of the phosphinyl oxygen that
enhances the phosphorus nucleophilicity and formation of
metal-ethoxide ion pairs that catalyzes the ethoxide nucleo-
philic attack on the phosphinate. By microscopic reversibility
it is possible that the metal ion could coordinate to a leaving
group, which in this case would be a tight ion pair between
an oxophilic alkali metal ion and the oxygen atom of
ethoxide.
Besides indicating a single mechanism for the P-S
scission process, the correlation with σ (R ) 0.993) instead
of σ- (see Supporting Information) is consistent with a
process which goes through an intermediate as shown in
Scheme 1 where M ) MoCp2. With the exception of aryl
dimethylphosphinate, all prior phosphinate and thiophosphi-
nate hydrolysis studies under alkaline conditions correlate
(23) Kim, J. H.; Chin, J. J. Am. Chem. Soc. 1992, 114, 9792.
(24) (a) Streitwieser, A.; Rajca, A.; McDowell, R. S.; Glaser, R. J. Am.
Chem. Soc. 1987, 109, 4184. (b) Rajca, A.; Rice, J. E.; Streitwieser,
A.; Schaefer, H. F.; McDowell, R. S.; Glaser, R. J. Am. Chem. Soc.
1987, 109, 4189. (c) Schmidt, M. W.; Gordon, M. S. J. Am. Chem.
Soc. 1985, 107, 1922.
(25) Cook, R. D.; Rahhal-Arabi, L. Tetrahedron Lett. 1985, 26, 3147.
(26) (a) Zhdankovich, E. L.; Eliseeva, G. D.; Baranskii, V. A.; Istomin, B.
I.; Voronkov, M. G. IzV. Akad. Nauk, Ser. Khim. 1983, 5, 1020. (b)
Istomin, B. I.; Eliseeva, G. D.; Kalabina, A. V. Zh. Obshch. Khim.
1980, 50, 1186. (c) Eliseeva, G. D.; Istomin, B. I.; Kalabina, A. V.
Zh. Obshch. Khim. 1980, 50, 1901. (d) Eliseeva, G. D.; Istomin, B.
I.; Kalabina, A. V. Zh. Obshch. Khim. 1978, 48, 1901.
This mechanism prompts us to ask if Cp2Mo coordination
to the sulfur leaving group plays a part in the P-S scission
chemistry especially in light of the fact that compound II
(27) Dunn, E. J.; Buncel, E. Can. J. Chem. 1989, 67, 1440.
5540 Inorganic Chemistry, Vol. 44, No. 15, 2005

Organometallic Complex Hydrolyzing Thiophosphinates
was one of the main products in the hydrolysis reaction and
that Cp2Mo coordination to sulfur-containing molecules is
well-known.18 Various ortho-substituted thiophenyl diphe-
nylphosphinates were made to sterically encumber possible
Cp2Mo coordination to the sulfur leaving group. These
derivatives were 2-methylthiophenyl and 2,6-dimethylth-
iophenyl diphenylphosphinate, and their rates of hydrolysis
by Cp2MoCl2 were measured relative to p-methylthiophenyl
diphenylphosphinate. The measured first-order hydrolysis
rates shows a drop of 2-3 in the rates of P-S scission by
Cp2MoCl2 when 2-methylthiophenyl and 2,6-dimethylth-
iophenyl diphenylphosphinate were hydrolyzed.
This drop in P-S scission rates with sterically encumbered
leaving groups becomes insignificant in light of the fact that
2-methylthiophenyl diphenylphosphinate by itself undergoes
P-S cleavage 2-3 times slower than the p-methylthiophenyl
derivative. The drop in the rate of hydrolysis may be an
inherit property caused by the steric hindrance of the five-
coordinate phosphorus intermediate of the ortho-substituted
thiol phosphinates.28 This suggests that metal coordination
to the leaving group (Scheme 2) either does not take place
or plays a minor role in P-S hydrolysis. Consistent with
this notion is the recent report by Tyler and co-workers who
showed that the hydrolysis of carboxylic esters by (MeCp)2-
Mo(OH)(OH2)2+ displayed no Mo(IV) coordination to the
alkoxide leaving group.29 The Mo-S bond strength in Cp2-
Mo complexes is reported to be 20-25 kcal/mol weaker than
the corresponding Mo-O bond;30 this further underscores
the fact that the Mo(IV) coordination to the sulfur leaving
group is not critical to the hydrolysis of thiol phosphinates.
Instead, the key pathway for the thiophosphinate hydrolysis
proceeds through Scheme 1 where M ) MoCp2.
Conclusion
We have shown the first case of an organometallic
complex that hydrolyzes thiol phosphinates through P-S
scission. Kinetics data are consistent with a mechanism that
involves intermolecular nucleophilic attack to form a five-
coordinate intermediate, which is the rate determining step,
followed by expulsion of the thiophenolate leaving group.
This mechanistic hypothesis is in accordance with the prior
phosphinate hydrolysis studies in alkaline solution. The rate
accelerations of the thiophosphinates by Cp2MoCl2 are
proposed to come from the binding of the phosphinyl oxygen
to the Mo(IV) center to increase the electrophilicity of the
phosphorus center for nucleophilic attack. These initial
findings lead us to examine the hydrolysis of phosphono-
thioates that have both thiolate and alkoxide leaving groups,
as means to see the viability of Cp2MoCl2 and its derivatives
as reagents to degrade organophosphorus neurotoxins.
Acknowledgment. A.P.B. and L.Y.K acknowledge the
financial support of Research Corporation and NSF-RUI for
this work, and the authors thank Dan Denevan (University
of Florida) for many helpful discussions and recommenda-
tions.
Supporting Information Available: X-ray crystallographic files
in CIF format for the structure determination of Cp2Mo(S-C6H4-
pOCH3)2 (II) and a graph of the absence of a correlation of the
rate of hydrolysis with σ-. This material is available free of charge
via the Internet at http://pubs.acs.org.
IC050819J
(28) Istomin, B. I.; Eliseeva, G. D., A. V. Zh. Obshch. Khim. 1981, 2063,
1186.
(30) Calhorda, M. J.; de C. T. Carrondo, M. A. A. F.; Dias, A. R.;
Domingos, A. M. T. S.; Martinho Simoes, J. A.; Teixeira, C.
Organometallics 1986, 5, 660.
(29) Brenno, K. L.; Pluth, M. D.; Landorf, C. W.; Tyler, D. R. Organo-
metallics 2004, 23, 1738.
Inorganic Chemistry, Vol. 44, No. 15, 2005 5541