Iron complexes with nitrogen bidentate ligands as green catalysts for alcohol oxidation

Article abstract of DOI:10.1016/j.molcata.2016.05.023

The iron(II) complexes [Fe(N-N)₃](OTf)₂ (N-N = 2,2′- bipyridine, 1,10-phenanthroline and substituted derivatives) were employed as catalyst precursors for the oxidation of primary and secondary alcohols, including glycerol. The single-crystal structure of [Fe(bipy)₃](OTf)₂ was determined by X-ray crystallography.The catalytic reactions were performed using either H₂O₂ or tert-butilhydroperoxide (TBHP) as oxidating agent, in mild experimental conditions: with all catalysts employed, secondary alcohols were oxidized to the corresponding ketones with up to 100% yields, whereas other substrates gave lower conversions. Indications on the nature of the catalytically active species, which is probably formed via dissociation of a nitrogen ligand from the iron center, were obtained from NMR and ESI-MS spectra.

Full text of DOI:10.1016/j.molcata.2016.05.023

Accepted Manuscript
Title: Iron complexes with nitrogen bidentate ligands as green
catalysts for alcohol oxidation
Author: Jennifer E. Ch a` vez Corrado Crotti Ennio Zangrando
Erica Farnetti
PII:
S1381-1169(16)30205-9
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcata.2016.05.023
MOLCAA 9898
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Journal of Molecular Catalysis A: Chemical
Received date:
Revised date:
Accepted date:
20-4-2016
13-5-2016
23-5-2016
Please cite this article as: Jennifer E.Ch a` vez, Corrado Crotti, Ennio Zangrando,
Erica Farnetti, Iron complexes with nitrogen bidentate ligands as green
catalysts for alcohol oxidation, Journal of Molecular Catalysis A: Chemical
http://dx.doi.org/10.1016/j.molcata.2016.05.023
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Iron complexes with nitrogen bidentate ligands as green catalysts
for alcohol oxidation
a
b
a
a,b
Jennifer E. Chàvez , Corrado Crotti , Ennio Zangrando and Erica Farnetti*
a
Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Trieste, Via L. Giorgieri 1, 34127 Trieste (Italy).
CNR – Istituto Struttura della Materia, Unità Operativa di Supporto di Trieste, S.R.14, Km163.5, 34149 Basovizza, Trieste (Italy).
b
*
Corresponding author. Phone: +39-040-5583938; Fax: +39-040-5583903.
E-mail address: farnetti@units.it. (E. Farnetti)
1

Graphical abstract
The iron(II) complexes [Fe(N-N) ](OTf) (N-N = 2,2’- bipyridine, 1,10-phenanthroline and substituted
3
2
derivatives) behave as catalyst precursors for the oxidation of primary and secondary alcohols, using
either H O or tert-butilhydroperoxide as oxidating agent in mild experimental conditions.
2
2
2

Highlights



Iron complexes with bipyridines or phenanthrolines catalyse oxidation of alcohols.
The reactions employ either H O or tert-butilhydroperoxide (TBHP) as oxidant.
2
2
NMR studies gave indications on the nature of the catalytically active species.
3

Abstract
The iron(II) complexes [Fe(N-N) ](OTf) (N-N = 2,2’- bipyridine, 1,10-phenanthroline and substituted derivatives) were
3
2
employed as catalyst precursors for the oxidation of primary and secondary alcohols, including glycerol. The single-crystal
structure of [Fe(bipy) ](OTf) was determined by X-ray crystallography.The catalytic reactions were performed using either
3
2
H O or tert-butilhydroperoxide (TBHP) as oxidating agent, in mild experimental conditions: with all catalysts employed,
2
2
secondary alcohols were oxidized to the corresponding ketones with up to 100% yields, whereas other substrates gave lower
conversions. Indications on the nature of the catalytically active species, which is probably formed via dissociation of a nitrogen
ligand from the iron center, were obtained from NMR and ESI-MS spectra.
Keywords
Iron catalysts, nitrogen ligands, oxidation, alcohols, glycerol.
4

Introduction
The recent development of transition-metal promoted organic synthesis has largely focussed on the replacement of catalysts
based on precious metals with first row transition-metal compounds. The urgency towards this target lies on the limited
availability as well as high price of platinum group metals on one hand and on their relevant toxicity on the other. Among the
possible candidates, iron has been emerging as the most attractive substitute due to its large availability, moderate price and low
toxicity; last but not least, iron compounds are environmentally benign [1]. The enormous increase of research on iron-based
catalysis is witnessed by a growing number of publications, among which some very recent examples concern olefin
hydrogenation [2] and epoxidation [3], reduction of carboxylic acid derivatives [4], amination of alcohols [5], alkynes
trimerization [6] and diazidation of olefins [7].
Since iron catalysts have a relevant role in biological redox systems, it is not surprising that the most important iron-promoted
processes so far developed include oxidation reactions [8]. In particular, regarding the oxidation of alcohols to carbonyl
compounds, which is a fundamental transformation in organic synthesis, iron-based catalysts are promising substitutes for the
traditional stoichiometric methods on one hand, and precious metal promoted oxidation on the other. Use of iron catalysts in
association with green oxidants such as peroxides, the reduced products of which (alcohols or water) are generally non-toxic [9],
is expected to provide highly sustainable oxidation processes.
Apart from early reports of alcohol oxidation catalyzed by iron salts [10], which proved sometimes effective but often poorly
selective, more recent papers describe the use of very efficient catalysts based on the association of iron with various polydentate
nitrogen-donor ligands [11] including porphyrines [12]. In contrast, examples of alcohol oxidation catalyzed by iron complexes
with bidentate ligands with either N or N,O donor atoms are less common [13].
We became interested in the development of iron-based oxidation catalysts which should combine appreciable catalytic activity
and selectivity with simple and low-cost catalyst synthesis: in other words, catalyst precursors having cheap, ready available
coordinated ligands. In addition, use of Fe(II) low spin complexes would offer the opportunity of gaining information on the
evolution of the catalytically active species by means of NMR studies. In fact, the mechanistic details of iron-promoted
oxidations are still unclear, in spite of recent efforts to shed light on this subject [14].
A further reason which called our attention towards alcohol oxidation lies in our interest on selective glycerol oxidation, a
process of high applicative importance: after developing iridium-based catalysts for the conversion of glycerol to
dihydroxyacetone, we recently reported the first example of such reaction promoted by an iron catalyst, i.e. [Fe(BPA) (OTf) ]
2
2
(BPA=bis(2-pyridinylmethyl)amine) [15].
In the following we describe our results in the oxidation of primary and secondary alcohols, including glycerol, catalyzed by iron
complexes with 1,10-phenanthroline, 2,2’- bipyridine and substituted derivatives, using either hydrogen peroxide or TBHP as
oxidant in very mild reaction conditions.
2. Experimental section
2
.1. General
All the chemicals were reagent grade and were used as received from the commercial suppliers, with the exception of
naphthalene, used as GC standard, which was recrystallized from ethanol.
2
.2. Instrumental
1H and 13C NMR spectra were recorded either on a Varian 500 spectrometer operating at 500 MHz and 125.68 MHz,
respectively, or on a Jeol EX400 spectrometer operating at 400 MHz and 100.4 MHz, respectively; chemical shifts were
measured relative to the residual solvent signal. Resonances were assigned with reference to COSY and HSQC spectra.
ESI-MS spectra were obtained by an ion-trap instrument (ESI-MS Bruker Esquire 4000) equipped with an electrospray ion
source. The instrument performed with 10.0 psi nebulizer pressure, end-plate offset -500 V, capillary 4000 V and capillary exit at
-
1
1
13.3 V. The drying gas (N ) flow was 5 L min and the spectral range was from m/z = 100 to 1200.
2
1
The chemical yields of the catalytic reactions were determined by integration of the H NMR signals and/or by GC analysis on an
Agilent 6850 instrument with helium as carrier gas and a TCD detector.
2
.3. Synthesis of the iron complexes
Synthesis of [Fe(bipy) ](OTf) (1)
3
2
A round-bottomed flask was charged with acetonitrile (3 mL) and Fe(OTf) (0.56 mmol), the yellow solution so obtained
2
immediately turned dark red upon addition of bipy (1.12 mmol). The reaction mixture was stirred at r.t. for 30 min and then
5

concentrated to 1/3 of the initial volume. Addition of diethylether caused precipitation of a dark red solid, which was filtered and
1
washed with ether. Yield 73%. H NMR (CD CN, 25°C): δ 8.56 (d, 2H, H and H ), 8.13 (t, 2H, H and H ), 7.42 (m, 4H, H
3
3
3’
4
4’
5
1
3
and H , H and H ). C NMR (CD CN, 25°C): δ 160.0 (C and C ), 155.0 (C and C ), 139.5 (C and C ), 128.3 (C and C ),
5
’
6
6’
3
2
2’
6
6’
4
4’
5
5’
1
24.8 (C and C ).
3 3’
Synthesis of [Fe(phen) ](OTf) (2)
Same procedure as for 1 but with ligand phen. Yield 71%. H NMR (CD CN, 25°C): δ 8.65 (d, 2H, H +H ), 8.29 (s, 2H, H +H ),
3
2
1
3
2
9
5
6
1
3
7
.69 (d, 2H, H +H ), 7.63 (dd, 2H, H +H ). C NMR (CD CN, 25°C): δ 156.2 (C +C ), 149.7 (C-N quat.), 137.4 (C +C ), 130.5
4 7 3 8 3 4 7 2 9
(
C quat.), 128.1 (C +C ); 126.0 (C +C ).
5 6 3 8
Synthesis of [Fe(DMbipy) ](OTf) (3)
Same procedure as for 1 but with ligand DMbipy (DMbipy = 4,4’-dimethyl-2,2’-bipyridine). Yield 80%. H NMR (CD CN,
3
2
1
3
1
3
2
5°C): δ 8.38 (s, 2H, H and H ), 7.21 (br, 4H, H and H , H and H ), 2.59 (s, 6H, Me). C NMR (CD CN, 25°C): δ 158.9 (C
3 3’ 5 5’ 6 6’ 3 2
and C or C and C ), 153.3 (C and C or C and C ), 151.2 (C and C or C and C ), 128.3 (C and C or C and C ), 124.7
2
’
4
4’
5
5’
6
6’
2
2’
4
4’
5
5’
6
6’
(
C and C ), 20.3 (Me).
3 3’
Synthesis of [Fe(DMphen) ](OTf) (4)
Same procedure as for 1 but with ligand DMphen (DMphen = 4,7-dimethyl-1,10 phenanthroline). Yield 75%. H NMR (CD CN,
3
2
1
3
1
3
2
5°C): δ 8.38 (s, 2H, H +H ), 7.51 (s, 2H, H +H ), 7.44 (s, 2H, H +H ), 2.89 (s, 6H, Me). C NMR (CD CN, 25°C): δ 156.2
2 9 5 6 3 8 3
(
C +C ), 150.4 (C quat.), 148.6 (C quat.), 131.1 (C quat.), 127.5 (C +C ), 125.5 (C +C ), 18.9 (Me).
5 6 3 8 2 9
2
.4. X-ray crystal structure analysis
Data collection of 1 was performed at the X-ray diffraction beamline (XRD1) of the Elettra Synchrotron of Trieste (Italy), with a
Pilatus 2M image plate detector. The experiment was performed at 100 K (nitrogen stream supplied by an Oxford Cryostream
7
00) with a monochromatic wavelength of 0.700 Å through the rotating crystal method. The diffraction data were indexed,
integrated and scaled using program XDS [16]. The structure was solved by direct methods using SIR2014 [17]. Fourier analysis
2
and refinement with the full-matrix least-squares method based on F were performed with SHELXL-2014 [18]. One triflate
anion was found disordered over two positions with refined occupancies of 0.850(3)/0.150(3), sharing one oxygen atom.
Hydrogen atoms were placed at calculated positions with isotropic U factors equal to 1.2 times the equivalent U factor of the
bonded atom.
Crystallographic data: C H F FeN O S , M = 822.54, monoclinic, space group C2/c, a = 36.417(3), b = 11.123(2), c =
3
2
24
6
6
6 2
3
3
-1
1
2
7.554(3) Å, β= 111.83(3)°, V = 6601(2) Å , Z = 8, Dc = 1.655 g/cm , ( Mo-K) = 0.674 mm , F(000) = 3344, θ range = 1.19 -
8.23°. Final R1 = 0.0624, wR2 = 0.1671, S = 1.073 for 508 parameters and 15945 reflections, 8154 unique [R(int) = 0.0279], of
which 7795 with I > 2(I), max positive and negative peaks in ΔF map 1.787, -1.512 e. Å . CCDC reference number 1473638.
-
3
2
.4. Procedure for the catalytic reactions
Oxidation of alcohols catalyzed by Fe(OTf) /N-N “in situ”.
2
A round-bottomed flask was charged with the solvent (3.0 mL), Fe(OTf) (0.050 mmol) and the nitrogen ligand (0.10 mmol).
2
After addition of the substrate (2.5 mmol), the oxidant was added dropwise under stirring, at r.t.. After the desired time the
reaction mixture was cooled at -18°C and subsequently analized by GC and/or NMR.
Oxidation of alcohols catalyzed by [Fe(N-N) ](OTf) .
3
2
In a round-bottomed flask the solvent (3.0 mL) and the catalyst precursor [Fe(N-N) ](OTf) (0.050 mmol) were introduced,
3
2
followed by the substrate (2.5 mmol). For reactions performed at temperatures higher than r.t., the resulting solution was heated
in a thermostatted bath to the desired temperature. Slow addition of the oxidant was then carried out under stirring. After the
desired time the reaction mixture was cooled at -18°C and subsequently analized by GC and/or NMR.
Oxidation of glycerol catalyzed by [Fe(N-N) ](OTf) .
3
2
Glycerol (2.5 mmol) was introduced into a round-bottomed flask, followed by the solvent (3.0 mL) and the iron catalyst (0.050
mmol). For reactions performed at temperatures higher than r.t., the resulting solution was heated in a thermostatted bath to the
desired temperature. The oxidant was then added dropwise under vigorous stirring. After the appropriate time the reaction
mixture was cooled at -18°C and subsequently analized by GC and/or NMR.
2
.5. Analysis of the reaction mixtures
1
13
Qualitative analysis was accomplished by H and C NMR; the resonances were compared with those of authentic samples
6

obtained either by conventional routes or by commercial suppliers. Quantitative evaluation of product distributions was
1
performed by integration of H NMR signals (in this case the catalytic reactions were performed in a deuterated solvent:
acetonitrile-d , acetone-d or D O) and/or by GC with naphthalene as the internal standard.
3
6
2
3. Results and discussion
3
.1. Synthesis and characterization of the iron precursors.
The oxidation reactions were initially carried out by employing a catalytic system prepared in situ from Fe(OTf) (OTf =
2
CF SO ) and two equivalents of 2,2’-bipyridine (bipy) and using 1-phenylethanol as substrate. Oxidant (H O ) and solvent
3
3
2
2
(acetonitrile) were chosen in agreement with Green Chemistry principles: the latter (classified as “usable” solvent) was selected
after exclusion of all “preferred” ones [19] due to poor solubility of reagents and/or competition with substrate. A first series of
test reactions thus performed gave promising results, i.e. acetophenone was formed in appreciable yield as the only reaction
product: these findings prompted us to isolate the Fe/N-N complex which behaved as catalyst precursor. Therefore, Fe(OTf)2
was treated on a preparative scale with 2 equivalents of bipy in acetonitrile at r.t., giving a purple-red solution from which, upon
1
addition of diethylether, a dark red solid (1) was isolated. The H NMR spectrum of this product in CD CN only showed three
3
1
3
resonances, a doublet at δ 8.56, a triplet at δ 8.13 and a rather broad signal at δ 7.42 of area 1:1:2, respectively. The C NMR
spectrum was accordingly simple, as it consisted of five signals at δ 160.0, 155.0, 139.5, 128.3 e 124.8.
In order to unambiguously characterize compound 1 suitable crystals were grown by slow diffusion of n-hexane into a
concentrated solution of 1 in acetonitrile. As shown in Figure 1, in spite of the stoichiometry employed (bipy/Fe=2) the resulting
complex was [Fe(bipy) ](OTf) , a well-known compound previously prepared by a different procedure [20]. The octahedral
3
2
complex presents Fe-N bond distances in the range 1.959(2) - 1.973(2) Å, in agreement with values measured in the numerous
2
+
reported [Fe(bipy)3] derivatives having different counterions.
Figure 1. Asymmetric unit of complex 1 (Ortep drawing, 50% probability ellipsoid). Coordination bond distances (Å) Fe-N(1) =
1
.973(2), Fe-N(2) = 1.960(2), Fe-N(3) = 1.965(2), Fe-N(4) = 1.959(2), Fe-N(5) = 1.965(2), Fe-N(6) = 1.9598(19).
By the same procedure three more iron complexes were synthesized (see Scheme 1), each one having a different coordinated
nitrogen ligand: thus, compounds [Fe(phen) ](OTf) (phen = 1,10-phenanthroline) (2), [Fe(DMbipy) ](OTf) (DMbipy = 4,4’-
3
2
3
2
dimethyl-2,2’-bipyridine ) (3) and [Fe(DMphen) ](OTf) (DMphen = 4,7-dimethyl-1,10-phenanthroline) (4) were obtained and
3
2
characterized on the basis of their NMR spectra (see Experimental Section).
Scheme 1. Synthesis of iron precursors.
7

3
.2. Oxidation of 1-phenylethanol (PE) with H O catalyzed by [Fe(N-N) ](OTf) .
2 2 3 2
Using compound 1 as catalyst precursor, oxidation of PE with hydrogen peroxide was performed in acetonitrile solution. The
results reported in Table 1 (entries 1-4) show that the yield of acetophenone after 30 min increased by increasing the reaction
temperature, ranging from 17% at 25 °C to 66% at 70 °C. After 30 min the conversion no longer increased. However, after 1h a
second addition of hydrogen peroxide promoted the overall conversion to a final 85%. (Table 1, entry 5).
Catalytic reactions carried out using 2, 3 or 4 as catalyst precursor under the same experimental condition gave similar results
(see Table 1, entries 6-9). Therefore, in the process under investigation the different properties of the nitrogen ligands in terms of
donor abilities [21] do not appear to influence the catalytic performance of the active species.
In all catalytic reactions above described the final conversion was attained within 30 min from the addition of H O : such
2
2
findings were ascribed to the well-known iron-catalyzed hydrogen peroxide decomposition [22]. With the aim of discouraging
such decomposition, another series of catalytic tests was performed in a different reaction medium: thus, acetonitrile was
replaced by acetone, which is known to have a beneficial effect on oxidations with H O as it stabilizes the peroxide releasing it
2
2
gradually [23]. As a matter of fact, at r.t. if on one hand after short reaction times the same conversions were obtained in acetone
and acetonitrile (compare entries 10 with 6 and 13 with 1 in Table 1), on the other hand the oxidation performed in acetone
proceeded for longer reaction times (Table 1, entries 11 and 14); also in this case, further addition of H O gave new impulse to
2
2
the catalytic reaction (Table 1, entries 12 and 15). However, when higher reaction temperatures were employed no beneficial
effect of using acetone was observed (Table 1, entries 16 and 17).
8

a
Table 1. Oxidation of 1-phenylethanol (PE) to acetophenone with H O catalyzed by [Fe(L) ](OTf) .
2
2
3
2
Entry
L
T (C°)
solvent
t (min)
[H O ]/[sub]
Yield (%)
17
2
2
1
bipy
25
CH CN
30
2
3
2
3
4
5
6
7
8
9
“
40
55
70
55
25
55
55
“
“
“
“
“
“
“
30
30
2
47
55
66
85
16
50
48
“
2
“
30
2
2 + 2
2
“
phen
“
120
30
30
2
DMPhen
30
2
DMBipy
phen
55
25
“
30
2
2
39
16
1
0
acetone
0.5
1
1
1
2
“
“
“
“
“
“
24
48
“
38
61
2 + 2
1
1
1
1
1
3
4
5
6
7
bipy
25
“
“
“
“
“
“
0.5
24
48
0.5
24
2
15
37
60
34
34
“
“
“
“
“
2 + 2
2
“
50
“
“
a
-2
Experimental conditions: [Fe]= 1.7×10 M; [sub]/[Fe]= 50; H O (aq) 30%.
2
2
9

3
.3. Oxidation of 1-phenylethanol with TBHP.
A series of catalytic reactions was performed using tert-butylhydroperoxide (TBHP) in place of H O : such replacement proved
2
2
beneficial to the outcome of the reactions. In the presence of complex 1 at 55 °C the reaction yields after 30 min with H O and
2
2
TBHP were 55% and 79%, respectively. Moreover, at 25 °C with all catalytic precursors 1-4 the reactions performed with TBHP
produced acetophenone with conversions around 80% after 2h (Table 2, entries 1, 3, 5, and 7) whereas in all cases 100%
conversion was achieved after 24h (Table 2, entries 2, 4, 6, and 8). Replacement of acetonitrile with acetone as reaction medium
caused no significant differences in the final conversion. Thus, with the catalytic systems under investigation TBHP behaved as a
more efficient oxidant than hydrogen peroxide, giving complete conversion at r.t., in contrast with lower yields obtained with
H O even at higher temperatures. In our previous studies on iron-promoted oxidation [15] we had found a reverse trend, as
2
2
hydrogen peroxide behaved as more efficient oxidant.
1
0

a
Table 2. Oxidation of 1-phenylethanol (PE) to acetophenone with TBHP catalyzed by [Fe(L) ](OTf) .
3
2
Entry
L
[L]/[Fe(L )(OTf) ]
t (h)
[sub]/[Fe]
Yield (%)
3
2
1
2
3
4
5
6
7
8
bipy
-
2
50
80
100
84
“
-
-
-
-
-
-
-
-
-
-
-
-
24
2
“
phen
“
“
24
2
“
100
89
DMBipy
“
“
24
2
“
“
100
78
DMPhen
“
24
24
24
24
24
24
“
100
85
b
9
bipy
“
1
1
1
1
0
1
2
3
“
“
“
“
100
250
50 + 50
3x50
100
90
100
100
1
1
1
4
5
6
“
“
-
24
2
4x50
50
90
6
3
3
phen
2
“
4
a
-2
b
Experimental conditions: [Fe]= 1.7×10 M; TBHP(aq) 70%; [TBHP]/[sub]= 2; T=25 °C. [TBHP]/[sub]= 1.
1
1

Use of a single equivalent of TBHP also gave conversions above 80% (Table 2, entry 9). Notably, even at increased [sub]/[Fe]
ratios conversions of 90% or higher were obtained (Table 2, entries 10, 11).
The stability of the catalyst was then examined, by adding new loads of both substrate and TBHP after complete oxidation of the
initial amount of PE: after two such additions complete oxidation was again observed, and even a forth load of substrate and
oxidant gave formation of acetophenone in 90% yield (see Table 2 entries 2 and 12-14).
Interestingly, when the catalytic reaction with complex 1 was repeated in the presence of 3 equivalents of added bipy we
observed a dramatic drop in acetophenone yield (6 % in 2h); an analogous reaction carried out with compound 2 and added phen
gave the same result (compare entries 1 with 15 and 3 with 16 in Table 2). These findings indicate that the catalytically active
species is formed via dissociation of one nitrogen chelating ligand from the iron center: such process is depressed by the presence
of added ligand, with consequent loss of catalytic activity.
3
.4. Oxidation of primary and secondary alcohols catalyzed by [Fe(bipy) ](OTf) .
3 2
The substrate scope of the catalytic reactions in the presence of complex 1 was examined with a series of primary and secondary
alcohols, as well as an unsaturated alcohol and a diol. In this investigation both hydrogen peroxide and TBHP were tested as
oxidating agents. A selection of the results is reported in Table 3: the catalytic system was effective for oxidation of nearly all
examined substrates. First of all, a comparison between oxidation of the model secondary and primary alcohols, i.e. PE and
benzyl alcohol, shows that with the latter substrate – which was oxidized to benzaldehyde - the extent of oxidation was lower,
independently on the choice of the oxidant (compare entries 1 and 2, 3 and 4 in Table 3). On the other hand, a catalytic reaction
performed by using an equimolar mixture of these two compounds showed no substrate selectivity, as in the final reaction
mixture both acetophenone and benzaldehyde were present in an approximate 2:1 ratio.
1
2

a
Table 3. Oxidation of alcohols catalyzed by [Fe(bipy) ](OTf) .
3
2
Entry
Substrate
Product
Yield (%)
OH
O
b
1
55
b
OH
O
2
35
OH
O
3
4
100
OH
O
52
49
66
OH
O
5
6
MeO
MeO
OH
O
O
OH
7
8
9
2
OH
OH
O
52
55
O
1
1
0
1
OH
O
2
O
OH
47
O
O
OH
OH
+
c
1
2
23
O
OH
a
-2
b
Experimental conditions: [Fe]= 1.7×10 M; [sub]/[Fe]= 50; ox= TBHP(aq) 70%; [ox]/[sub]= 2; T= 25 °C; t= 24h. T= 55 °C;
c
ox= H O (aq) 30%; t= 30 min; yields 11% ketoalcohol and 12% diketone.
2
2
1
3

Aliphatic primary alcohols were oxidized only in traces to the corresponding aldehydes, whereas an allylic alcohol (cinnamyl
alcohol) was converted to the corresponding unsaturated aldehyde (cinnamaldehyde) with appreciable yield (see Table 3 entries
7
, 10 and 6, respectively).
Aliphatic secondary alcohols (2-butanol, cyclopentanol and cyclohexanol) were oxidized to the corresponding ketones with
comparable yields (Table 3, entries 8, 9, and 11); finally, 2,3-butandiol was converted to a 1:1 mixture of the corresponding
ketoalcohol and diketone (Table 3 entry 12).
3
.5. Oxidation of glycerol catalyzed by [Fe(bipy) ](OTf) .
3 2
As already mentioned in the Introduction, the selective oxidation of glycerol is a process of extremely high importance, all the
possible products being of interest from an industrial point of view. The first step of this process is the oxidation of either one
primary hydroxyl group to give glyceraldehyde or the secondary hydroxyl group forming dihydroxyacetone (DHA) (see Scheme
2
), the latter product being the most desirable one in terms of commercial value. We recently showed that iron can catalyze this
process with selective formation of DHA, as proved by the results obtained with [Fe(BPA) (OTf) ] (BPA = bis(2-
2
2
pyridinylmethyl)amine ) [15].
The results discussed in the previous paragraph indicate a preference of the catalytic systems under investigation towards
oxidation of secondary alcohols in comparison to primary ones: thus, compounds 1-4 appeared potentially suitable catalysts for
the selective oxidation of glycerol to DHA.
Therefore, we carried out a series of reactions with complexes 1-4 as catalyst precursors and glycerol as substrate. (see selected
results in Table 4). The final reaction mixtures using acetonitrile as solvent and either hydrogen peroxide or TBHP as oxidant
contained DHA as the main product albeit in yields not exceeding 4%, along with traces of other products (glyceraldehyde,
glycolic acid) (see entries 1-5 in Table 4).
Scheme 2. Products of glycerol oxidation.
Other catalytic tests were performed using water in place of acetonitrile as reaction medium, in association with H O as
2
2
oxidating agent: such modification caused an increase of the overall conversion, however the major product was now formic acid
FA), with yields of DHA not exceeding 5% (Table 4, entries 6 and 7). At variance, reactions carried out in water with TBHP
(
gave lower yields in both FA and DHA (Table 4, entry 8). Notably, FA is a valuable product both as as hydrogen carrier [24] and
as convenient source of C1 raw material for the chemical industry [25]; formation of FA as the main product of iron-caralyzed
oxidation of glycerol was very recently reported by our group [26].
In conclusion, association of iron(II) with bipy, phen or their substituted derivatives does not produce efficient catalysts for the
selective oxidation of glycerol to DHA, in contrast to that of ligand BPA.
1
4

a
Table 4. Oxidation of glycerol catalyzed by [Fe(bipy) ](OTf) .
3
2
DHA
yield (%)
FA
yield (%)
Entry
Solvent
T ( C°)
t (h)
Oxidant
[ox]/[sub]
1
2
CH CN
25
55
24
H O
2
2
2
1
0
0
3
2
2
“
0.5
H O
2
2
3
4
“
“
25
55
24
TBHP
TBHP
2
2
2
3
0
0
0.5
5
6
7
8
“
70
70
70
70
2
2
2
2
TBHP
H O
2
1
2
2
4
5
4
2
0
22
49
6
H O
2
2
2
“
“
H O
2
2
TBHP
a
-2
Experimental conditions: [Fe]= 1.7×10 M; [sub]/[Fe]= 50; oxidant: H O (aq) 30% or TBHP (aq) 70%; DHA=
2
2
dihydroxyacetone; FA= formic acid.
1
5

3
.5. NMR and ESI-MS studies of the oxidation of PE catalyzed by [Fe(bipy) ](OTf) .
3 2
With the aim of following the evolution of the iron precursors in the course of the catalytic process, the NMR spectra of samples
prepared for this purpose were recorded before, during and after completion of the oxidation reaction.
In a first experiment we followed the oxidation of cyclohexanol with TBHP in the presence of complex 1: the starting solution
was prepared in CD CN with a lower substrate concentration ([sub]/[Fe]=10) than that usually employed, in order to identify
3
more clearly the resonances of the iron complexes (the same reason motivated the choice of a substrate which has no resonances
in the aromatic region). The NMR spectra of the solution were recorded in three moments, with reference to addition of TBHP:
(i) before the addition, (ii) 1h after the addition and (iii) 24h after the addition (the sample was stored at -18°C overnight).
1
13
H and C NMR spectra of sample (i) displayed the resonances of complex 1 and those of the substrate, whereas the absence of
signals assignable to cyclohexanone indicated that no aerobic oxidation had taken place. In sample (ii) the catalytic reaction was
1
underway, the H NMR spectrum showed very broad signals attributable to the presence of paramagnetic iron intermediates.
1
Finally, in the H NMR spectrum of sample (iii) rather narrow signals were once more observed, indicating that no
paramagnetic species were present in significative amount: besides the signals of cyclohexanone the spectrum comprised those of
complex 1, accompanied by smaller resonances at δ 8.86, 8.52, 8.43 and 7.90, referable to a new iron/bipy compound (5) (see
Figure 2), which we were unable to identify due to its very low concentration.
In order to gain further indications on the evolution of the iron precursor we acquired the ESI-MS spectra of samples (i) and (iii).
2
+
The mass spectrum of sample (i) showed a major peak at m/z 184, assignable to Fe(bipy) , accompanied by a smaller signal at
2
2
+
+
m/z 262 correspondent to Fe(bipy)3 ; a very small peak at m/z 361 assignable to Fe(bipy)(OTf) was also present. Sample (iii),
obtained at the end of the catalytic reaction, had MS signals identical to those observed for sample (i), but for the absence of the
2
+
peak of Fe(bipy)3 at m/z 262. Notably, in both samples no other signals assignable to further iron complexes were detected.
When the same NMR analysis above described was repeated using the same three-steps procedure, but in the presence of added
bipy ([bipy]/[1]=3), the spectra of samples (i) and (iii) showed a single notable difference, i.e. the absence in the final solution of
the signals of the new iron species 5.
1
Figure 2. Region of aromatic protons of H NMR spectrum (CD CN) of the final reaction mixture of oxidation of cyclohexanol
3
catalyzed by 1.
1
6

These findings, in association with the results of the catalytic reactions discussed in the previous paragraph, support the
hypothesis of dissociation of one bipy from complex 1 to give the catalytically active species, to which the iron species 5 present
in the final solution is probably related. Conversely, in the presence of free bipy the dissociation of one ligand from the iron
center is repressed, resulting in nearly complete suppression of the catalytic activity (see Table 2, entry 15) and in the consequent
absence of complex 5 in the final reaction mixture. As a matter of fact, formation of the catalyst via dissociation of a nitrogen
chelating ligand from the precursor was previously proposed in iron-catalyzed processes [27].
With regard to the nature of the catalytically active species, the very broad signals observed in the NMR spectra 1h after addition
of the peroxide suggest the formation of paramagnetic iron species in higher oxidation state. It is well known that in oxidation
reactions the presence of iron in association with H O may give rise to the classical free radical mechanism, with indiscriminate,
2
2
poorly selective reactivity, as opposed to metal-based mechanism, i.e. the desirable catalysis. When iron complexes with nitrogen
polydentate ligands are used as catalysts, such reactions are believed to occur via a metal-based mechanism, whereas hydroxyl
radicals do not seem to be involved [11a-b, 14a, 20, 28]. According to mechanistic studies, initial reaction of the iron precursor
with hydrogen peroxide gives an iron-peroxo, which in turn is transformed into a Fe(IV) or Fe(V)=O complex, the likely
catalytically active species. Support to this hypothesis was provided by trapping high-valent iron-oxo intermediates at low
temperature [29].
4. Conclusions
The iron compounds 1-4 with coordinated bipy, phen or substituted derivatives proved to be efficient catalysts for the oxidation
of primary and secondary alcohols with hydrogen peroxide or TBHP. Although the ability of iron complexes to catalyze this
reaction has been well documented, the present work introduces as catalyst precursors well characterized compounds in which
with iron is associated to simple nitrogen bidentate ligands, at variance with most examples of iron oxidation catalysts previously
reported with coordinated polydentate ligands which must be synthesized by a multi-step procedure. In spite of the preferred
oxidation of secondary alcohols observed, selective oxidation of glycerol to DHA was not attained. The evolution of the iron
precursor in the course of the catalytic reaction, monitored by NMR and ESI-MS, provided support to the hypothesis of
formation of the catalytically active species via dissociation of one nitrogen ligand. Notably, the catalytic reactions here
described are all examples of sustainable processes in terms of choice of catalyst (both metal and ligand), nature of oxidant and
solvent as well as experimental conditions.
Acknowledgements
Financial support from the University of Trieste (FRA 2014) is gratefully acknowledged.
1
7

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1
8

Captions to Figures and Schemes.
Figure 1. Asymmetric unit of complex 1 (Ortep drawing, 50% probability ellipsoid). Coordination bond distances (Å) Fe-N(1) =
1
.973(2), Fe-N(2) = 1.960(2), Fe-N(3) = 1.965(2), Fe-N(4) = 1.959(2), Fe-N(5) = 1.965(2), Fe-N(6) = 1.9598(19).
Scheme 1. Synthesis of iron precursors.
Scheme 2. Products of glycerol oxidation.
1
Figure 2. H NMR spectrum (CD CN) of the final reaction mixture of oxidation of cyclohexanol catalyzed by 1.
3
1
9