Amination of Aryl Chlorides
FULL PAPER
ucts leads to a new anionic catalytic species that makes the
secondary cycle gain importance with time. For this reason,
both cycles appear to be linked throughout the reaction
progress in a cooperative way: the rate decrease of the regu-
lar neutral cycle as conversion increases is compensated by
the secondary anionic cycle.
It is believed that both cycles 1 and 2 involve mononu-
clear Pd species; these species could not be identified be-
cause of their exceptionally high reactivity. Deduced from
3
1
the P NMR spectroscopic and X-ray diffraction studies re-
ported here, one of the two Pd atoms of 1 is easily lost upon
addition of NaOtBu—the base used in stoichiometric quan-
tities in the catalytic process and a key element for the out-
standing reactivity of 1 in amination reactions.
The stability of the catalyst has been also addressed. It
has been found that in the absence of substrates to process,
the active catalytic species readily experiences cyclopallada-
tion with geometrically available CÀH bonds in the phos-
Figure 9. Components analysis of the reaction rate. Inset: expansion of
the profiles at higher conversion (conversion increases from right to left).
cycle 2 exceeds that operating in cycle 1. Nonetheless, both
cycles contribute similarly to the overall reaction rate be-
cause cycle 2 is intrinsically slower than cycle 1, which can
seen from the rate constants for the irreversible reaction
phine ligand. This could be a common mechanism of decom-
position for Pd–monophosphine ligand complexes.
Although detailed structural information on catalytically
active species derived from 1 could not be obtained, our
work provides valuable information and guidelines for fur-
ther studies (e.g. by computational means). Our results also
bear implications for further improvements to the valuable
aromatic amination reaction by suppression of product in-
hibition in the primary catalytic cycle and the slower, yet
active, secondary cycle. It is likely that secondary anionic
catalytic cycles also operate in other amination reactions
catalyzed by palladium complexes. These slower, yet impor-
tant, catalytic reaction pathways were apparently unnoticed
in previous kinetic studies that focused only on initial rates
of reaction.
À1
À1
steps (k =30.8 versus k =0.33m min ).
12
22
Although anionic cycles based on chloride binding are
[32]
usually faster than neutral mechanisms, it seems that in
this particular case only the oxidative addition is accelerat-
ed. This would lead to an overall slower secondary cycle
that would eventually predominate due to the increasing
concentration of chloride ions. To confirm this hypothesis,
sodium chloride (10 mol% with respect to 2) was added at
the beginning of the reaction and a marked decrease in the
rate of product formation was observed. Moreover, almost
total inhibition was observed when tetrabutylammonium
chloride (a fully soluble source of chloride anions) was used
as an additive (see the Supporting Information for details).
To discount any effect due to the tetrabutylammonium
Experimental Section
[33]
cation,
an additional experiment was performed in the
Typical kinetic experiment: Reagents and precatalyst 1 were stored in a
glovebox, and anhydrous solvents were used. Reactions were carried out
in a jacketed, three-necked, heart-shaped glass reactor thermostatized at
presence of lithium chloride (20 mol%), which is more solu-
ble in THF. Inhibition was again observed; conversion after
[34–36]
1
h decreased from 54% (control experiment) to 34%.
2
58C. Measurements were taken with an in situ ReactIR apparatus
Thus, these results strongly indicate that the interaction of
chloride anions with the catalyst leads to an alternative,
slower mechanism, which is in full agreement with the kinet-
ic studies reported above.
equipped with a diamond probe immersed in the reaction mixture. A
À1
representative signal corresponding to product formation ( n˜ =1611 cm
)
was tracked. The reaction vessel was heated at 1108C for 1 h under a ni-
trogen flow, then cooled to 408C and the background IR spectrum was
collected. Sodium tert-butoxide (534 mg, 5.56 mmol) and catalyst
16.6 mg, 0.0278 mmol) were introduced. The vessel was simultaneously
purged with nitrogen and cooled to 258C. A solution of 2 (329 mL,
.78 mmol) and 3 (328 mg, 3.06 mmol) in anhydrous THF (5 mL) was
1
(
2
Conclusion
added by syringe under vigorous stirring (1000 rpm). Recording of the IR
spectra was started immediately after the addition.
The amination of p-chlorotoluene (2) with p-toluidine (3) in
the presence of the dinuclear palladium complex 1 involves
a complex mechanistic scenario. According to the kinetic
analysis, the reaction is subject to product inhibition and
two distinct catalytic cycles are involved in the overall proc-
ess. The two cycles contribute differently to the formation of
the final product. Additionally, their contributions change
continuously as the reaction progresses. The appearance of
chloride anions in the medium as one of the reaction prod-
Acknowledgements
This work was funded by MINECO (grants CTQ2008–00947/BQU and
CTQ2012–38594-C02–01), DEC (Grant 2009SGR623), and the ICIQ
Foundation. C.J. thanks MICINN for a Ramꢇn y Cajal contract. We
thank Profs. V. Grushin and R. Martin (ICIQ) for helpful discussions,
technical assistance, and the generous gift of reagents.
Chem. Eur. J. 2012, 18, 16510 – 16516
ꢅ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
16515