Inorganic Chemistry
ARTICLE
6aꢀg at pH14 11.7 in methanol exhibited a sharp downward
reduced pressure overnight to give 0.45 g of the complex as white
powder in 77% yield. This procedure is similar to the one proposed
for the preparation of (μ-CF3SO3)2[Pd(dmba)]2;18 however,
NMR and HRMS analyses confirm the identity of the isolated
complex as the acetonitrile-containing complex. In our hands, all
attempts to prepare the (μ-CF3SO3)2[Pd(dmba)]2 dimer without
acetonitrile in the reaction mixture resulted in rapid formation of
palladium black.
s
s
break suggestive of a process where there is a change in rate
limiting step, implying the existence of one or more intermedi-
ates along the reaction pathway. The large negative βlg value
of ꢀ1.93 for the descending wing of the Brønsted plot is
conspicuously large for simple cleavage of the P-OAr bond as
it exceeds the theoretical βeq for transfer of the (MeO)2PdS
group between oxyanion nucleophiles.15
Pd(II)(2-(N,N-dimethylaminobenzylamine)-C1,N)(CH3CN)(triflate):
1H NMR (400.3 MHz, δ ppm, CD3OD, 25 °C): δ 7.04 (m, 1H), 6.97
(d, J = 7.3 Hz, 1H), 6.90 (m, 2H), 4.01 (s, 2H), 2.76 (s, 6H), 2.08
(br, 3H); 19F NMR (376.5 MHz, δ ppm, CD3OD, 25 °C): δ ꢀ81.1;
HRMS(ESI+ TOF in MeOH): calcd for C12H19N2OPd [Pd(II)(2-(N,
N-dimethylaminobenzylamine)-C1,N)(CH3CN)(HOMe)]: calcd m/z
313.0532 amu; found 313.0559 amu. mp 72ꢀ74 °C.
Herein we describe results of detailed kinetic studies of the
sspH/rate profiles for cleavage of 6aꢀg promoted by 5 which
indicate there are three changes in rate limiting step in passing
from the required active form 5a to products. This suggests
involvement of three essential forms of the palladacycle. These
are 5a and two subsequent complexes having the same stoichi-
ometry, namely, a first formed complex 5:(ꢀOCH3):6, and a
subsequent palladacycle-stabilized 5-coordinate thiophosphor-
ane intermediate, 7. The latter intermediate, never before
observed, is sufficiently stabilized to allow visualization by UV/
visible spectrophotometry and determination of the rate con-
stants for its equilibrium formation and breakdown. Finally, we
present a detailed analysis that shows that the original large nega-
tive coefficient for the steep wing of the Brønsted plot previously
reported13 results from a combination of an equilibrium process
(βeq = ꢀ1.04) between the starting materials and the thiopho-
sphorane intermediate, and the process involving subsequent
leaving group departure with a βlg value of ꢀ0.96.
2.2. Kinetics for Reactions Catalyzed by 5. The methanolyses
of phosphorothioate triesters 6aꢀg in the presence of 5 were monitored
by UV/vis spectrophotometry at 25.0 °C. In general, a UV-cell (1 cm
path length) was charged with 0.05 mM of substrate 6 and a 1ꢀ3 mM
buffer solution in anhydrous methanol. The latter were composed of
various ratios of HClO4 and amines (2,4,6-collidine (sspH = 7.8ꢀ8.5),
N-isopropylmorpholine (sspH = 8.5ꢀ9.0), 1-methylpiperidine (sspH =
9.4ꢀ9.7), 1-ethylpiperidine (sspH = 9.8ꢀ10.5), triethylamine (sspH =
10.9), and 2,2,6,6-tetramethylpiperidine (TMPP; sspH = 11.0ꢀ12.2)) to
maintain the desired sspH. No inhibition was observed with these buffers
between 0.4 and 5.0 mM. For reactions conducted at higher sspH values,
0.5ꢀ10 mM of NaOMe was introduced to maintain a constant [ꢀOMe].
Reactions were initiated by injecting the appropriate amount of catalyst
stock solution into the buffer/substrate mixture so that the final [5] =
0.08 mM in 2.5 mL of buffered methanol. The reaction progress was
followed by the appearance of the phenolic products at 393 (6a), 314 or
390 (6b), 320 or 400 (6c), 330 or 365 (6d), 284 or 292 (6e), 273 (6f),
and 292 nm (6g) depending on the sspH. Faster reactions were followed
to at least three half-times and fitting the abs. vs time traces to a standard
exponential model gave the pseudofirst order rate constants (kobs).
Slower processes were studied by initial rate methods. The second order
rate constants (k2cat) for the methanolysis of 6c promoted by 5 and 5b
(data shown in the Supporting Information, Figures S1 and S2) were
determined from fitting the plots of kobs vs [catalyst] to a linear
regression forcing the line through the origin. Reported rate constants
are the averages of duplicate runs. It is important to point out that when
the [catalyst] e [substrate], good first order behavior was found with full
release of the expected phenolic product at the end of the reaction,
indicating catalyst turnover with no observable product inhibition. This
is due to the fact that equilibrium binding of the catalyst and the
substrate/product is quite weak,13 and so the [catalyst] remains con-
stant, satisfying the pseudofirst order conditions. Stock solutions of 5b
(produced from 5c dissolved in methanol) where the palladacycle exists
with either a weakly associated acetonitrile or solvent, develop a light
brownish color (indicative of the formation of Pd nanoparticles or
palladium black) after two days at room temperature, even with limited
exposure to the atmosphere. Thus, these stock solutions were always
freshly prepared prior to the kinetic experiments. By contrast, stock
solutions of the pyridine-containing palladacycle 5 in neutral methanol
are relatively stable, with no signs of color change or loss of reactivity for
at least 10 days at room temperature.
2. EXPERIMENTAL SECTION
2.1.1. Materials and Methods. Sodium methoxide (0.5 M solu-
tion in methanol, titrated against N/50 Fisher Certified standard
aqueous HCl solution and found to be 0.49 M), tetrabutylammonium
hydroxide (1.0 M solution in methanol, titrated to be 1.05 M), Ag-
(CF3SO3) (99%+), Pd(Cl)2 (g99.9%), 4-(dimethylamino)pyridine
(DMAP, 99%), 2,4,6-collidine (99%), triethylamine (99%), and 2,2,6,6-
tetramethylpiperidine (99+%) were obtained from Aldrich. 1-Methyl-
piperidine (99%) and 1-ethylpiperidine (99%) were obtained from Alfa
Aesar and TCI America Laboratory Chemicals, respectively. HClO4
(70% aqueous solution, titrated to be 12.3 M) and N,N-dimethylbenzy-
lamine (dmba, 99%) were from Acros Organics. Anhydrous methanol
was supplied by EMD chemicals. Phosphorothioates 6aꢀg and catalyst
5 came from an earlier study.13 Caution! All these phosphorothioate
substrates are acetylcholinesterase inhibitors and should be handled with
great care.
+
The CH3OH2 concentrations were determined potentiometrically
using a combination glass electrode (Radiometer model XC100ꢀ111ꢀ
120ꢀ161) calibrated with Fisher certified standard aqueous buffers
(pH = 4.00 and 10.00) as describedin a previous paper.16 The sspH values14
in methanol were obtained by subtracting a correction constant of ꢀ2.2416
from the electrode readings with the autoprotolysis constant for meth-
s
s
anol taken as 10ꢀ16.77 M2. A listing of the pKa values of different sub-
stituted phenols in methanol can be found in a previous account.17
2.1.2. Preparation of Complex 5c. [Pd(II)(2-(N,N-dimethy-
laminobenzylamine)-C1,N)(CH3CN) (triflate)]. To a stirring solution
of 0.377 g (0.686 mmol) of (μ-Cl)2[Pd(dmba)]2 dimer in anhydrous
CH2Cl2 (20 mL) was slowly introduced Ag(CF3SO3) (0.355 g, 1.387
mmol) in anhydrous acetonitrile (2 mL). The mixture was allowed to stir
at room temperature for 5 min, and the white precipitate formed was
removed by filtration. The solvent was removed from the clear filtrate
under reduced pressure to yield a yellow solid. The solid was redissolved
in ∼1 mL of CH2Cl2, and the complex precipitated out of the solution as
a fluffy off-white powder upon the addition of ∼5 mL of pentane. This
was washed with 2 ꢁ 5 mL portions of pentane and then dried under
2.3. Initial Rate Determination for 5-Catalyzed Methano-
lyses of 6a and 6c. These were conducted in a UV-cell with TMPP
buffer (sspH = 11.6 ( 0.1) and substrates 6a or 6c (from 0.01ꢀ0.10 mM)
in anhydrous methanol. The reactions were initiated by adding aliquots
of a methanolic stock solution of 5 to the mixtures which, at this sspH,
instantly forms 5a so that the final [5a] and TMPP were 0.08 mM and
2 mM in 2.5 mL of methanol. The appearance of phenoxide products
was followed at 400 nm and the first 5ꢀ10% of the abs. vs time traces
7853
dx.doi.org/10.1021/ic201062h |Inorg. Chem. 2011, 50, 7852–7862