The unexpected role of pyridine-2-carboxylic acid in manganese based oxidation catalysis with pyridin-2-yl based ligands

Article abstract of DOI:10.1039/c0dt00452a

A number of manganese-based catalysts employing ligands whose structures incorporate pyridyl groups have been reported previously to achieve both high turnover numbers and selectivity in the oxidation of alkenes and alcohols, using H₂O₂ as terminal oxidant. Here we report our recent finding that these ligands decompose in situ to pyridine-2-carboxylic acid and its derivatives, in the presence of a manganese source, H₂O ₂ and a base. Importantly, the decomposition occurs prior to the onset of catalysed oxidation of organic substrates. It is found that the pyridine-2-carboxylic acid formed, together with a manganese source, provides for the observed catalytic activity. The degradation of this series of pyridyl ligands to pyridine-2-carboxylic acid under reaction conditions is demonstrated by ¹H NMR spectroscopy. In all cases the activity and selectivity of the manganese/pyridyl containing ligand systems are identical to that observed with the corresponding number of equivalents of pyridine-2-carboxylic acid; except that, when pyridine-2-carboxylic acid is used directly, a lag phase is not observed and the efficiency in terms of the number of equivalents of H ₂O₂ required decreases from 6-8 equiv. with the pyridin-2-yl based ligands to 1-1.5 equiv. with pyridine-2-carboxylic acid.

Full text of DOI:10.1039/c0dt00452a

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HOT ARTICLE:
The unexpected role of pyridine-2-carboxylic acid in manganese based oxidation catalysis with
pyridin-2-yl based ligands
Dirk Pijper, Pattama Saisaha, Johannes W. de Boer, Rob Hoen, Christian Smit, Auke Meetsma,
Ronald Hage, Ruben P. van Summeren, Paul L. Alsters, Ben L. Feringa and Wesley R. Browne
Dalton Trans., 2010, DOI: 10.1039/C0DT00452A
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PAPER
www.rsc.org/dalton | Dalton Transactions
The unexpected role of pyridine-2-carboxylic acid in manganese based
oxidation catalysis with pyridin-2-yl based ligands†‡
Dirk Pijper,a Pattama Saisaha,a Johannes W. de Boer,b Rob Hoen,a Christian Smit,a Auke Meetsma,a
Ronald Hage,b Ruben P. van Summeren,c Paul L. Alsters,c Ben L. Feringaa and Wesley R. Browne*a
Received 10th May 2010, Accepted 10th June 2010
DOI: 10.1039/c0dt00452a
A number of manganese-based catalysts employing ligands whose structures incorporate pyridyl
groups have been reported previously to achieve both high turnover numbers and selectivity in the
oxidation of alkenes and alcohols, using H2O2 as terminal oxidant. Here we report our recent finding
that these ligands decompose in situ to pyridine-2-carboxylic acid and its derivatives, in the presence of
a manganese source, H2O2 and a base. Importantly, the decomposition occurs prior to the onset of
catalysed oxidation of organic substrates. It is found that the pyridine-2-carboxylic acid formed,
together with a manganese source, provides for the observed catalytic activity. The degradation of this
series of pyridyl ligands to pyridine-2-carboxylic acid under reaction conditions is demonstrated by 1H
NMR spectroscopy. In all cases the activity and selectivity of the manganese/pyridyl containing ligand
systems are identical to that observed with the corresponding number of equivalents of
pyridine-2-carboxylic acid; except that, when pyridine-2-carboxylic acid is used directly, a lag phase is
not observed and the efficiency in terms of the number of equivalents of H2O2 required decreases from
6–8 equiv. with the pyridin-2-yl based ligands to 1–1.5 equiv. with pyridine-2-carboxylic acid.
Introduction
The design of new ligands for 1st row transition metal oxidation
catalysts has been driven by the desire to reduce the reliance
on stoichiometric oxidants (e.g., MnO4 , OsO4, peracids etc.),1
-
and to replace 2nd and 3rd row transition metal based oxidation
catalysts.2,3 A key challenge this presents is to achieve high activity
while at the same time avoiding oxidative degradation of ligands
during catalysis. Indeed ligand stability has been a longstanding
issue in transition metal oxidation catalysis, as exemplified by the
design rules proposed by Collins as early as 1994.4,5
The focus on ligand stability is important since, although
ligand free oxidation catalysis can be achieved with manganese
as demonstrated by Burgess and co-workers,6 in order to control
reactivity and especially (enantio) selectivity then it is almost
certainly unavoidable that ligand metal complexes are employed.
Over the last decades many ligand systems have been developed
that have proven their effectiveness with iron and manganese
during oxidation catalysis, including the pyridyl based ligand
families (e.g., TPEN,20 BPMEN,7 TPA8 and N4Py,9 Fig. 1) and
the paradigm tmtacn ligand (where tmtacn is N,N¢,N¢¢-trimethyl-
Fig. 1 Examples of pyridyl and triazacyclononane based ligands em-
ployed in Fe and Mn based oxidation catalysis.
1,4,7-triazacylononane, Fig. 1),10 which has proven one of the
more effective ligands for manganese based oxidation catalysis.11
The stability of these systems have allowed for stereospecific C–H
activation,12 (enantioselective) epoxidation13,14 and (enantioselec-
tive) cis-dihydroxylation of alkenes,15–18 often with high turnover
numbers and efficiency in terminal oxidants, e.g., peracetic acid
and H2O2.
Nevertheless, many ligand systems that have been employed in
oxidation catalysis to date have been limited due to their propensity
to undergo oxidative degradation, as demonstrated for instance
by Banse, Girerd and coworkers19 for the TPEN20 class of ligands
(Fig. 1). Oxidative ligand degradation can be inhibited, as shown
by Banse and coworkers recently,21 through introduction of steric
hindrance in the TPEN ligand. Degradation via C–H abstraction
was reduced, an effect ascribed to inhibition of bimolecular
degradation pathways. Britovsek and coworkers22 have reported
also that catalytic activity and catalyst stability (with respect to
ligand dissociation) correlate in the non-heme iron catalyst family.
aStratingh Institute for Chemistry, Faculty of Mathematics and Natural
Sciences, University of Groningen, Nijenborgh 4, 9747AG, Groningen,
The Netherlands. E-mail: w.r.browne@rug.nl; Fax: 0031-50-363-4279;
Tel: 0031-50-363-4428
bRahu Catalytics BV, BioPartner Center Leiden, Wassenaarseweg 72, 2333,
AL Leiden, The Netherlands
cDSM Innovative Synthesis, PO Box 18, 6160 MD, Geleen, The Netherlands
† Based on the presentation given at Dalton Discussion No. 12, 13–15th
September 2010, Durham University, UK.
‡ Electronic supplementary information (ESI) available: Full synthesis
and characterisation of ligand, details for catalysis experiments and
ligand decomposition studies. CCDC reference number 768839. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/c0dt00452a
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Dalton Trans., 2010, 39, 10375–10381 | 10375
©

This may account for the stability observed in multidentate ligands
where ligand dissociation is of limited importance (vide supra).
These observations are important as the primary tools available
to tuning the catalytic activity and selectivity of transition metal
complexes is to change reactions conditions, in particular solvent,
co-catalysts and pH, and to vary the detailed structure of the
ligands—both of which can affect coordinative stability and ligand
robustness in addition to catalyst performance.
related ligands (4–7, 13–16, Fig. 3) we obtain essentially identical
reactivity and selectivity as that observed for the TPEN based
ligands reported previously.
This aspect is exemplified for instance by the oxidation catalyst
[MnIV2O3(tmtacn)2]2+. De Vos,11b,11d Berkessel,11e Lindsay Smith,23
Feringa15,17,18 and co-workers have demonstrated that varying
the solvent and co-catalyst employed has a profound effect
on its activity. For example tuning selectivity from selective
epoxidation to selective cis-dihydroxylation of alkenes.17 It has
been demonstrated by Feringa and co-workers that the complex
reacts with the carboxylic acid co-catalysts in situ, to complexes
of the type [MnIII2O(RCO2)2(tmtacn)2]2+ that are responsible for
the activity achieved.17,18 An alternative strategy taken recently
by Costas and co-workers is to tune reactivity by modifying the
tmtacn ligand with an additional pyridyl group (Pyr-Me2tacn,
Fig. 1).24 The catalysts formed by this complex with manganese24
and iron25 show markedly different reactivity and selectivity under
acidic conditions compared with [MnIV2O3(tmtacn)2]2+. In both
approaches the ligand itself has proven to be robust with catalyst
deactivation proceeding by ligand dissociation rather than ligand
oxidation.
Fig. 3 Ligands employed in the present study.
The key finding we report is that in all cases these ligands (2–7,
13–16) are highly unstable under the catalytic conditions employed
and undergo rapid decomposition, ultimately, to pyridine-2-
carboxylic acid. We show that the catalytic activity observed
for a wide range of pyridyl based ligands (2–7, 13–16) under
certain conditions is as a direct result of the pyridine-2-carboxylic
acid formed in situ. Unexpectedly, instead of leading to reduced
activity, oxidative ligand degradation allowed for the discovery of
a remarkably simple yet powerful four component catalytic system
for a wide range of oxidative transformations (i.e. pyridine-2-
carboxylic acid/MnII/NaOAc/carbonyl compound, Scheme 1).29
In general, most research effort has focused on this latter
approach, i.e. ligand modification, with attention being directed
especially towards the design of novel ligands based on pyridyl
metal binding moieties.26
Over a decade ago, we took such an approach by developing
a family of manganese complexes, with TPEN/TPTN type of
ligands (Fig. 1).27,28 Manganese complexes based on these pyridyl
ligands were indeed found to display high oxidation activity, both
in the epoxidation of alkenes27 and towards alcohol oxidation.28
An attractive feature of this type of ligands is that the synthetic
route allows for facile introduction of different groups both on the
central diamine unit or in replacing one or more of the pyridyl
rings.29 Although similar levels of activity could be achieved
compared with the tmtacn family of complexes, the manganese
catalysts based on these pyridyl containing ligands27 typically
require excess of oxidant (8–16 equiv. of H2O2) to overcome the
extensive catalase activity that follows addition of the H2O2 at the
start of the reaction.
Scheme 1 Alkene oxidation with H2O2. For the electron deficient alkene
diethyl fumarate full selectivity in favour of cis-dihydroxylation is observed
with ligands TPTN, 2–7 and pyridine-2-carboxylic acid (for which 0.3
mol% and only 1.5 equiv. of H2O2 was required for full conversion, vide
infra).
Results
An interesting question arises as to whether the intermediate
compounds 2 and 3 in the synthetic route to the TPEN type
ligands—i.e. intermediates containing an aminal ring motif (Fig.
2)— are also potential ligands in their own right.
Ligands 2–16 (Fig. 2 and 3) were prepared by standard methods
based on the procedure described by Mialane et al.30 and charac-
terised by NMR spectroscopy, elemental analysis and HRMS (see
ESI‡). TPTN (Fig. 1.) was described earlier.28
Catalytic activity of MnII with TPTN, 2 and 3
Previously we reported the activity of dinuclear MnII acetato
complexes of the TPTN ligand in the oxidation of alkenes27 and
benzyl alcohols.28 In the present study we have re-examined this
ligand together with the immediate synthetic precursors of TPEN
and TPTN, i.e. 2 and 3, respectively.
Fig. 2 Pyridine-2-carboxylic acid (1) and aminal ligands 2 and 3.
In the present contribution we describe the catalytic activity
observed with these aminal and other ligands with manganese
in the oxidation of alkenes. With these ligands and a series of
A typical example of the conditions used in the manganese
catalyzed oxidation reactions is shown in Scheme 1. The reaction
was found to proceed with conversion in acetone and butanone
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t
but not in acetonitrile or BuOH/H2O with TPTN, 2 and 3.
isolate the corresponding FeII complexes. Reaction of ligand 2
or 3 with one equivalent of FeII(ClO4)2 in methanol/acetontrile
lead over 30 min to 1 h to the appearance of an intense purple
coloration. Slow evaporation of solvent provided crystals of a
complex obtained from 3 suitable for single crystal structure
determination (see the experimental section, Fig. 4). From
X-ray crystallographic analysis together with elemental analysis
it is apparent that the central aminal ring of ligand 3 is opened
to release pyridin-2-carboxaldehyde (as a methoxy-hemiacetal)
followed by coordination of the ligand fragments to FeII. Attempts
to isolate MnII complexes of ligands 2 and 3 were unsuccessful to
date, however it should be noted that similar ligands have been
employed previously32 with MnII ions and in these cases the aminal
ring was found to be stable.
Furthermore, the addition of several equivalents of base, either
with the manganese source (e.g., MnII(OAc)2, or MnIII(OAc)3) or
as NaOAc, NaOH or Na2CO3 (when MnII(ClO4)2 is used) was
found to be essential. With other carboxylates such as sodium
trichloroacetate or benzoate the rate of reaction was substantially
decreased but full conversion was nevertheless achieved.
As noted earlier,27,28 the addition of at least 8 equiv. of H2O2
is required in order to obtain reasonable conversion of the
alkene substrates, due to the extensive disproportionation that is
observed initially upon addition of H2O2. The time dependence of
product formation/substrate consumption indicates a substantial
lag-time (~20–60 min) prior to the start of substrate conversion.
The addition of acid, e.g., acetic acid or trichloroacetic acid
suppressed catalase type activity completely, however in these
cases conversion of the substrate or even consumption of the
H2O2 was not observed. For diethyl fumarate full conversion to
the cis-diol product (d/l-diethyl tartrate) and for cis-cyclooctene
full conversion to a 1 : 6 mixture of cis-diol and epoxide product
was observed for TPTN, 2 and 3.
The identical reactivity and selectivity observed for TPTN and
ligands 2 and 3 was unexpected (vide infra). The observation of a
significant induction period during which extensive disproportion-
ation of H2O2 was observed prior to onset of substrate conversion
indicated that the formation of the active catalyst system was
slow. Mass spectral analysis of samples from the reaction mixture
using TPTN over the course of the catalyzed oxidation of alkenes
with H2O2, MnII and TPTN, indicated that TPTN undergoes
conversion to ligand 3 in this period.31
Fig. 4 Ortep representation of the iron complex isolated from the reaction
of FeII(ClO4)2 with ligand 3 in acetonitrile–methanol. Counter ions and
solvent of crystallisation are omitted for clarity.
Stability of ligands 2 and 3 in the presence of iron salts and under
acid and basic conditions
The stability of TPEN and TPTN with iron33 contrasts markedly
with the instability of their aminal precursors (e.g., 2 and 3).
This makes the observation of essentially identical reactivity and
selectivity with Mn/H2O2 all the more remarkable. A structure
activity study was therefore carried out to identify the key ligand
components required to achieve full activity.
The stability of TPEN and TPTN in the presence of iron and
manganese salts under non-oxidative conditions is evidenced by
the ability to prepare iron and manganese complexes from these
ligands (vide supra).19,20,27,28 However, for the ligands containing an
aminal motif, the stability is expected to be less. The stability of
1
ligand 2 was determined by H NMR spectroscopy under both
acidic and basic conditions in acetone and in the absence and
presence of H2O2.
Catalytic activity of MnII/ligand in relation to ligand structure
In the presence of excess trichloroacetic acid (4 equiv.) in acetone
ligand 2 was found to convert to a mixture of species within 2 h
both in the absence and presence of H2O2 (see ESI, Section 4a‡).
After 24 h, however, where only trichloroacetic acid was added,
The dependence of the observed reactivity and the structure
of the aminal ligand was investigated using a series of ligands
shown in Fig. 3. In this series of ligands the pyridyl groups were
systematically removed from the aminal ring and replaced with
other aromatic rings or else methyl groups. Furthermore the non-
cyclic ligands 13–16 (Fig. 3) were examined including ligands
containing the 6-methyl-pyridyl motif.
The catalytic activity of the series of aminal based ligands 2–12
in the oxidation of cis-cyclooctene was examined. Full conversion
with ligands 2–7, all of which contained at least one pyridin-
2-yl moiety, was observed with the cis-diol:epoxide ratio being
identical in all cases. By contrast ligands 8–12, which do not
contain a pyridine-2-yl unit, showed no activity in the oxidation
of cis-cyclooctene.
1
the H NMR spectrum recovered to show only absorptions due
to ligand 2. In the presence of H2O2 and trichloroacetic acid the
absorptions of 2 reappeared partially after 24 h (see ESI, Section
4b‡). This recovery of the original spectra with time is indicative of
partial hydrolysis under strongly acidic conditions, which reverses
as moisture from the air reduces the acidity of the solution.
In the presence of NaOH (4 equiv.) and/or H2O2 (8 equiv.)
1
ligand 2 was found to be stable with no change in the H NMR
spectrum over 24 h (see ESI, Section 4c/d‡). This indicates that
under the conditions relevant to the catalysed reactions, i.e. in
acetone/H2O with a base and H2O2, the aminal based ligands are
in fact stable to ring opening in the absence of metal ions.
An indication of the intrinsic instability of the aminal ligands
in the presence of metal ions was obtained during attempts to
The relative selectivity observed for four substrates with ligands
2–8 was examined (Table 1). The substrates chosen were diethyl
fumarate and n-butylacrylate, which are converted to the (cis-)diol
product exclusively, styrene, which shows an approximately equal
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Dalton Trans., 2010, 39, 10375–10381 | 10377
©

Table 1 Conversions and product distributions using ligands 2, 4, 7
and 8
What is certain, however, is that in the absence of a pyridin-2-yl
unit, activity is not observed. For ligands 13–15, which do not have
the aminal structural motif, essentially identical selectivity and
activity was observed in the oxidation of cis-cyclooctene compared
to ligand 2.
Substrate
Ligand
Conversiona
Product distributionb
2
4
7
8
100%
100%
100%
0%
cis-diol product only
(d/l-diethyl tartrate)
Ligand stability under reaction conditions
The stability of the ligands TPTN, 2, 3 and 4 under reaction
conditions was determined by H NMR spectroscopic analysis
2
4
7
8
82%
80%
75%
0%
1
diol product only
epoxide : diol 1 : 2
epoxide : diol 6 : 1
of the reaction mixture after catalysed oxidation of 2,3-dimethyl-
1
but-2-ene in acetone-d6. The H NMR spectrum of the diluted
reaction mixture was recorded 16 h after addition of H2O2 was
complete (Fig. 5).
2
4
7
8
25%
20%
22%
0%
2
4
7
8
100%
100%
95%
0%
yield of epoxide
79%c
2
13
48%c
15
100%
79%c
16
80%c
TPTN
58%c
a Reaction conditions: at 0 ◦C, substrate (1 M), Mn(ClO4)2·6H2O
(0.1 mM), ligand (0.1 mM), NaOAc (1.0 mM) in acetone with 8 equiv.
of H2O2. Conversion of substrate was determined by in situ Raman
spectroscopy by monitoring the decrease of the alkene stretching band
at ca. 1620 cm-1 with 1,2-dichlorobenzene as internal standard and
confirmed by H NMR spectroscopy, b Product yield was determined by
1
1H NMR spectroscopy. c Reaction conditions: at 0 ◦C, cis-cyclooctene
(1 M), Mn(OAc)3·2H2O (0.1 mM), ligand (0.1 mM) in acetone with 9.6
equiv. of H2O2. Conversion of substrate and yield of epoxide product was
determined by GC (diol not determined).
Fig. 5 1H NMR (400 MHz) spectra of the reaction mixture (Scheme 2)
with TPTN in acetone-d6 a) before and b) 16 h after addition of H2O2 and
c) pyridine-2-carboxylic acid (Scheme 2 and ESI‡ for details).
Due to the relatively low concentration of the ligand, the
spectrum is dominated by the absorptions of the substrate,
solvent and water. However, the absorptions corresponding to the
aromatic protons of the ligand are well-resolved.34 Fig. 5 shows
mixture of epoxide and cis-diol products and cis-cyclooctene,
which leads the epoxide product primarily but with a minor
amount of the cis-diol product also.
1
For ligand 8 no activity was observed for any of the substrates
examined. By contrast for ligands 2, 4 and 7 essentially identical
conversion and selectivity was observed for all substrates.
From Table 1 it is apparent that a minimum of one pyridine-2-yl
group is required in the structure of the ligand in order to obtain
substrate conversion, since for ligands 8–12, which lack a pyridin-
2-yl group in their structures, conversion is not observed. These
observations could be assigned to simply the denticity of the ligand
especially considering that in the presence of iron the aminal ring
is opened readily yielding ligands analogous to those shown in
Fig. 1. Furthermore, no significant effect of ligand structure on
conversion or product distributions are observed between ligands
2, 4 and 7. The instability of the aminal ring in the case of ligands 2,
3 and 7, could indicate that the loss of pyridine-2-carboxaldehyde
is the cause of the activity seen. However, for ligands 4–6 the
opening of the aminal ring does not lead immediately to free
pyridin-2-carboxaldehyde, yet full activity is nevertheless observed
for these ligands.
the H NMR spectrum of pyridine-2-carboxylic acid in acetone-
d6, together with the spectrum of the reaction mixture (Scheme
2) after 16 h where the ligand employed is TPTN. The spectrum
shows the ligand has decomposed to pyridine-2-carboxylic acid.
For ligands 2, 4 and 5 (see ESI‡) essentially the same effect was
observed with pyridine-2-carboxylic acid being detected (together
with benzoic and thiophene carboxylic acids, respectively) as the
principle aromatic component after oxidation reactions (see ESI‡).
Scheme 2 Conditions employed for studying ligand decomposition
during the oxidation of alkenes with H2O2 in acetone-d6.
Confirmation that the degradation products of the ligands, e.g.
7, were responsible for the catalytic activity observed was obtained
from the comparison of the oxidation of cis-cyclooctene and
diethyl fumarate where 8 and 4 equiv., respectively, of H2O2 were
Notably, the activity observed for ligands such as 13–15 (Fig. 3)
indicates that opening of aminal ring and/or facile loss of pyridine-
2-yl units from the ligand is not required to achieve full activity.
10378 | Dalton Trans., 2010, 39, 10375–10381
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©

added in a single addition or batchwise (see ESI‡). For both cis-
cyclooctene and diethyl fumarate, full conversion was observed
overnight when all the H2O2 was added at once. By contrast
addition of half of the H2O2 achieved only partial conversion
(<20%) overnight. Addition of the remaining H2O2 to these
reactions resulted in full conversion.
2–7 etc.) that, together with manganese ions, is responsible for the
catalytic activity observed.
C–H activation and alcohol oxidation with pyridine-2-carboxylic
acid/MnII/NaOAc
The ability of the system pyridine-2-carboxylic acid/MnII/NaOAc
to engage in oxidative degradation of the pyridyl ligands investi-
gated in the present study requires that the system can engage
in activation of C–H bonds and as well as in aryl-alcohol and
aldehyde oxidation. Although C–H activation35 is not observed
when alkene substrates are employed; for cyclooctane and tetra-
line, good conversion (>70%) and good selectivity to the mono-
ketone at (40–50%) is observed using both pyridin-2-carboxylic
acid or ligands 2–7. Furthermore, as for TPTN,28 toluene and
benzyl alcohol can be oxidised to benzaldehyde and eventually
benzoic acid with pyridine-2-carboxylic acid/MnII/NaOAc (see
ESI‡ for details).
Oxidation catalysis with pyridine-2-carboxylic acid/MnII
Recently, we reported a remarkably simple system capable of
efficient cis-dihydroxylation of electron deficient alkenes and
epoxidation of electron rich alkenes.29 This system comprises
of pyridine-2-carboxylic acid, a base (e.g., NaOH, or NaOAc)
and MnII source (typically at 0.1–0.3 mol%) in combination
with acetone and H2O2. The discovery of this system was as a
direct result of the mechanistic studies of the series of Mn/ligand
catalysts (Fig. 3) systems involving polypyridyl based ligands
reported here.
The observation of pyridine-2-carboxylic acid as the principle
decomposition product of ligands 1, 2, 4, 5 and TPTN indicates
that it may either be a manifestation of catalyst deactivation only
or that pyridine-2-carboxylic acid could in fact be responsible for
the catalytic activity observed. The observation that a lag period
is present after addition of H2O2 to the, e.g., 2/Mn catalysed
reactions, during which extensive disproportionation of H2O2 is
observed, followed by an second phase in which H2O2 is not
disproportionated and oxidation of substrates proceeds provides
a strong indication that decomposition products of the ligands are
responsible for catalysis.
The ability of pyridine-2-carboxylic acid together with MnII
to catalyse oxidation of alkenes was compared with that of
ligand 2 (Table 2). For three substrates used for comparison
identical results in terms of conversion and product formation
using either the aminal ligand or pyridine-2-carboxylic acid were
observed (Scheme 1, Table 2). Furthermore, whereas 4–8 equiv.
of H2O2 are required to achieve full conversion with the pyridyl
ligands, with pyridine-2-carboxylic acid the efficiency in oxidant
is substantially higher with only 1.5–2 equiv. of H2O2 required
for full conversion. These data provide compelling evidence that
under the reaction conditions, it is pyridine-2-carboxylic acid
rather than the pyridine-2-yl ligands (including TPTN, ligands
Discussion
In the present study we have shown that pyridin-2-yl ligands (2–
7, 13–16) undergo facile decomposition under mildly basic con-
ditions in acetone with Mn/H2O2 to yield pyridine-2-carboxylic
acids. It is apparent that the pyridine-2-carboxylic acid formed
by this ligand decomposition can fully account for the reactivity
observed towards oxidation of alkenes, alcohols and for the C–
H activation observed for ligands 2–7, 14, 15 and TPTN with
Mn/H2O2.
It is important to note that the conditions employed determine
the activity observed. For example under acidic conditions these
complexes show relatively little activity and especially those
ligands that do not incorporate an aminal ring motif are stable
towards decomposition. Furthermore, under mildly acidic condi-
tions (1–20 mol% acetic acid w.r.t. substrate) the reactivity of the
pyridine-2-carboxylic acid system is reduced considerably.29
For (chiral) ligand systems similar to those under consideration
in the present study, Stack and co-workers,36 have reported under
acidic conditions with peracetic acid and Costas and co-workers,24
with acetic acid/H2O2 that with MnII activity is observed which
cannot be ascribed to the formation of pyridine-2-carboxylic acids.
Furthermore, it is important to stress that in acetonitrile or other
non-ketone containing solvent systems, the system pyridine-2-
carboxylic acid/Mn/NaOAc is essentially inactive.29 The only, and
perhaps key, exception to this is that pyridine-2-carboxaldehyde
is oxidised readily to pyridine-2-carboxylic acid in acetonitrile in
the presence of Mn and H2O2.29 Hence, in these solvent systems
oxidative ligand degradation will lead to a suppression of activity,
as indeed has been noted by Banse, Girerd and co-workers for
TPEN.19
Table 2 Conversions and product distributions using aminal ligands 2 or
pyridine-2-carboxylic acid (1)
Substrate
Ligand
Conversiona
Product distributionb
2
1
100%
100%
cis-diol product
(d/l-diethyl tartrate)
2
1
20%
20%
cis-diol product
(meso-diethyl tartrate)
Notwithstanding this, it is clear that the methylene C–Hs of
pyridine-2-yl based ligands are susceptible to oxidation via C–H
activation as certainly occurs for the ligands (2–6) examined here.
In the case of the aminal based ligands the susceptibility to ring
opening and hydrolysis with a Lewis acidic metal could be viewed
as key to the in situ formation of pyridine-2-carboxylic acid. In the
case of ligands 4, 15 and TPTN, however, activity comparable to
that observed for an equivalent amount of pyridine-2-carboxylic
2
1
100%
100%
epoxide : cis-diol 6 : 1
a Conditions: 0.1 mol% Mn(ClO4)2. 6H2O, 0.1 mol% 2 or 0.3 mol%
pyridine-2-carboxylic acid, 1.0 mol% NaOAc and 8 equiv. H2O2 in acetone
at 20 ◦C. Conversion of substrate was determined by Raman spectroscopy
after 16 h. b Product yield and distribution were determined by 1H NMR
spectroscopy.
This journal is
The Royal Society of Chemistry 2010
Dalton Trans., 2010, 39, 10375–10381 | 10379
©

acid was observed (vide supra) and hence the opening of the aminal
ring is not an only factor.
omitted due to unreliability in their quantification by the GC
method used.
Caution. The drying or concentration of acetone solutions that
potentially contain hydrogen peroxide should be avoided. Prior to
drying or concentrating, because of the potential presence of H2O2
and other peroxides neutralisation on solid NaHSO3 or another
suitable reducing agent should be performed. When working with
H2O2, especially in acetone, suitable protective safeguards should
be in place at all times.39
Caution. Perchlorate salts are potentially explosive in combi-
nation with organic solids and solvents. In the present study
Mn(OAc)2, Mn(OAc)3 or MnSO4 were found to give essentially
identical reactivity and should be used above 2 gram reaction
scales.
Conclusions
In conclusion, we have found that for a class of ligands (2–
16 and TPTN) that feature ortho-pyridyl functionalities, which
have proven, when combined with manganese salts, to be active
oxidation catalysts in acetone using H2O2, it is actually the
pyridine-2-carboxylic acid formed in situ via decomposition of
the ligand under the oxidative conditions, that is responsible
for the observed catalytic activity. We have demonstrated the
degradation of the ligand to pyridine-2-carboxylic acid by 1H
NMR spectroscopy, and that replacement of ligand 2 by equivalent
amounts of pyridine-2-carboxylic acid in the oxidation reactions
results in identical activity and selectivity for a broad range of
substrates. The only notable difference being that with pyridine-
2-carboxylic acid much less H2O2 is required to achieve the same
levels of conversion.
Synthesis and characterisation of [Fe(N,N¢-Bis(pyridin-2-
ylmethyl)propane-1,3-diamine)(pryidyl-2-aldehyde-methoxy-
hemiacetal)](BF4)2·CH3CN
A solution of Fe(ClO4)2·H2O (0.15 g, 0.58 mmol) in acetonitrile
(2 mL) was added to a solution of ligand 3 (0.2 g, 0.58 mmol) in
methanol (4 mL) (Scheme 3). NaClO4 (0.14 g, 1.16 mmol) was
added to the mixture and the resulting solution was placed in
an EtOAc bath for three days changing colour from yellow to
intense purple within 1 h. The solvent was removed in vacuo and
the residue washed with Et2O and pentane to remove free ligand.
The residue was redissolved in a minimum of acetonitrile and
Ligand degradation is typically considered as a cause of catalyst
deactivation. The observation in this case is that in situ ligand
degradation to relatively simple compounds results in a highly
active oxidation system. This demonstrates the relevance of
mechanistic understanding of catalyzed reactions, not only in the
sense of elucidating catalytic cycles, but crucially in understanding
the catalytic system. For example, activity observed with the
ligand TPTN in acetonitrile with peracetic acid36 is due to very
different species than those involved in acetone with H2O2. This
includes the interplay of all of its components, as a whole through
speciation analysis. This is especially the case when understanding
the effect of variation in ligand structure on reactivity and
selectivity. Furthermore, it is an important consideration when
understanding how changes in solvent and additives tune the
reactivity of a particular system.
placed in an EtOAc bath yielding red coloured crystals (0.35 g, 0.52
2-
mmol, 89%). Elemental analysis calcd for C23H29.5Cl2FeN5.5O10
:
C 41.25%, H 4.44%, N 11.50%; found C 41.31%, H 4.51%, N
11.53%.
Experimental
All reagents are of commercial grade and used as received unless
stated otherwise. Hydrogen peroxide was used as received as a 50%
wt solution in water; note that the grade of H2O2 employed can
affect the reaction negatively where sequestrants are present as
stabilizers. Diethyl-2-methylfumarate37 was prepared by literature
procedures. NMR spectra were recorded at 1H-NMR (400.0 MHz)
and 13C-NMR (100.6 MHz). Chemical shifts are denoted relative
to the residual solvent absorption (1H: CDCl3 7.26 ppm; 13C:
CDCl3 77 ppm, acetone-d6 2.05 ppm).38 Raman spectra were
recorded using a fibre optic equipped dispersive Raman spectrom-
eter (785 nm, Perkin Elmer RamanFlex). Temperature was con-
trolled using a cuvette holder equipped with a custom made fibre
optic probe holder (Quantum Northwest). 1,2-Dichlorobenzene
was employed as internal standard for Raman spectroscopy.
GC analyses were performed on a Hewlett Packard 6890 Gas
Chromatograph equipped with an autosampler, using a HP-1
dimethyl polysiloxane column or a HP-5 5% phenylmethylsiloxane
column. Calibration was performed using authentic samples of the
alkenes and epoxides. Conversions, yields and turnover numbers
Scheme 3
X-Ray crystallography [C22H28FeN5O2]2+·2[ClO4]-·0.5(C2H3N),
Mr = 669.77, monoclinic, C2/c, a = 37.597(4), b = 9.1237(10),
◦
3
˚
˚
c = 16.3513(18) A, b = 102.216(1) , V = 5481.9(10) A , Z = 8,
Dx = 1.623 g cm-3, F(000) = 2768, m = 8.12 cm-1, l(Mo-Ka)
˚
= 0.71073 A, T = 100(1) K, 21142 reflections measured, GooF =
1.058, wR(F2) = 0.1118 for 5616 unique reflections and 397 param-
eters, and R(F) = 0.0444 for 4780 reflections obeying Fo ≥ 4.0 s(Fo)
criterion of observability. The asymmetric unit consists of four
moieties: a cationic Fe-complex, two perchlorate anions and an
half of an acetonitrile solvate molecule. The acetonitrile molecule
is located on a twofold axis. CCDC reference number 768839.‡
Acknowledgements
The authors acknowledge the Netherlands Organization for
Scientific Research (NWO, Project No. 700.57.428) VIDI (WRB,
PS) for financial support.
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©