Mechanistic Inferences Derived from Competitive Catalytic Reactions
COMMUNICATIONS
Scheme 4 (for aniline-based amines) and major-minor Materials
kinetics as in scenario II in Scheme 3 and Scheme 4
Anhydrous toluene was purchased from Aldrich and stored
over molecular sieves. The sodium tert-butoxide (Aldrich)
was stored in a glove box and vacuum-dried prior to use;
the benzophenone hydrazone (Acros) was stored in a fridge
and used without further purification. Tridecane (Aldrich),
palladium acetate (Sigma–Aldrich) and Binap (Aldrich)
were used as received.
(for aliphatic amines).[10] Since they did not report ac-
tivities for the separate reactions, it is difficult to dis-
cern if any of their examples correspond to the “mo-
nopolizing” system of scenario III that characterizes
the competitive reaction of hydrazone amines studied
here.
We may generalize this discussion to highlight im-
plications for other types of competitive reactions, the
most common example being given by kinetic resolu-
tions. In such a case we should consider that the selec-
tivity factor may depend not solely on the relative
ratio of the first-order rate constants, as typically de-
rived for kinetic resolutions.[11] This has implications
for the study of kinetic resolutions where strongly dif-
ferentiated binding can lead to high selectivity in a
competitive reaction network, as was recently dis-
cussed by Lloyd-Jones and Blackmond[12] in the con-
text of the kinetic resolution of azlactones via hydrol-
ysis studied by Tokunaga and coworkers[13]. Indeed,
this concept may be used as a principle for the design
Standard Conditions
In the competitive reaction the palladium acetate (10.1 mg,
0,045 mmol), binap (38.4 mg, 0.06 mmol), sodium tert-butox-
ide (269 mg, 2.8 mmol), benzophenone hydrazone (244.9 mg,
1.25 mmol), hexylamine (129.7 mg, 1.28 mmol), tridecane
(149.6 mg, 0.811 mmol) as the internal standard, were added
together to the reaction vessel, which was then placed in the
calorimeter and heated to 908C. Thermically equilibrated 3-
bromobenzotrifluoride (524.6 mg, 2.33 mmol) was injected
to the thermically equilibrated reaction mixture after
60 min. The final conversion was measured by GC on a
quenched sample.
and mechanistic diagnosis of efficient catalysts for ki- Sampling Experiment
netic resolutions.[14,15]
A sampling experiment was performed to verify that the
In conclusion, these findings suggest that a caution-
ary note is appropriate when either separate or com-
petitive reactions are used alone in a mechanistic
study, as in the separate investigation of single enan-
tiomer reactions to simplify the study of catalytic ki-
netic resolutions, or when competitive catalytic reac-
tions are employed to construct a Hammett plot. Our
results demonstrate that experimental trends as well
as mechanistic conclusions drawn from study of the
competitive reactions may not be in accord with those
obtained from the reactions studied separately. Com-
bining study of separate and parallel reactions may,
however, lead to important mechanistic insights. This
work reveals how the comparison of results from sep-
arate and competitive reactions provides kinetic and
mechanistic information about relative binding and
reactivity of intermediate species that would not be
conversion calculated from the calorimetric data was equal
to the conversion calculated from GC. Samples were taken
at regular intervals, quenched in water/toluene mixture at
ambient temperature and analyzed by GC.
For the benzophenone reaction the conversion was calcu-
lated from the equation:
For the hexylamine reaction the equation was:
The conversion of the halide was the sum of these two
accessible from study of the individual catalytic reac- conversions:
tions alone.
Supporting Information
Experimental Section
Full details of of the NMR and mass spectroscopic experi-
ments are given in the Supporting Information
Instrumentation
Reactions were carried out in an Omnical Insight CPR 220
reaction calorimeter, in which the instantaneous enthalpy
balance around the vessel was continuously monitored. The
sample vessel was a 15-mL septum-cap vial, and the volume
of the reactive solution was approximately 5 mL. The data
were then manipulated using the ꢁReaction progress kinetic
analysisꢂ technique as described in Ref.[4]
Acknowledgements
DGB, JSM and ACFacknowledge a CASE award and finan-
cial support from Syngenta. DGB holds a Royal Society of
Chemistry Wolfson Research Merit Award.
Adv. Synth. Catal. 2008, 350, 1007 – 1012
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1011