C-scorpionate iron(II) complexes as highly selective catalysts for the hydrocarboxylation of cyclohexane

Article abstract of DOI:10.1016/j.ica.2019.02.035

The C-scorpionate iron(II) complexes [FeCl₂{κ³-HC(pz)₃}] (1) (pz = pyrazol-1-yl), Li[FeCl₂{κ³-SO₃C(pz)₃}] (2) and the new [FeCl₂{κ³-HOCH₂C(pz)₃}] (3) act as catalysts for the hydrocarboxylation of cyclohexane (with CO and H₂O) to cyclohexanecarboxylic acid in a remarkable yield (up to 60%) and under mild conditions. The catalysts selectivity for the acid can be tuned by CO pressure, catalyst amount and reaction temperature. Complex [FeCl₂{κ³-HC(pz)₃}] (1) provides the most effective catalyst requiring low CO pressure. This work constitutes an unprecedented use of iron complexes as catalysts for the hydrocarboxylation of alkanes.

Full text of DOI:10.1016/j.ica.2019.02.035

Accepted Manuscript
Research paper
C-scorpionate iron(II) complexes as highly selective catalysts for the hydrocar-
boxylation of cyclohexane
Inês A.S. Matias, Ana P.C. Ribeiro, Elisabete C.B.A. Alegria, Armando J.L.
Pombeiro, Luísa M.D.R.S. Martins
PII:
S0020-1693(19)30101-X
https://doi.org/10.1016/j.ica.2019.02.035
ICA 18798
DOI:
Reference:
To appear in:
Inorganica Chimica Acta
Received Date:
Revised Date:
Accepted Date:
18 January 2019
21 February 2019
24 February 2019
Please cite this article as: I.A.S. Matias, A.P.C. Ribeiro, E.C.B. Alegria, A.J.L. Pombeiro, L.M.D. Martins, C-
scorpionate iron(II) complexes as highly selective catalysts for the hydrocarboxylation of cyclohexane, Inorganica
Chimica Acta (2019), doi: https://doi.org/10.1016/j.ica.2019.02.035
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C-scorpionate iron(II) complexes as highly selective catalysts for the hydrocarboxylation
of cyclohexane
1
1
1,2
1
Inês A.S. Matias, Ana P.C. Ribeiro, Elisabete C.B.A. Alegria, Armando J.L. Pombeiro,
1
,*
Luísa M.D.R.S. Martins
1
Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Universidade de
Lisboa, Portugal.
2
Chemical Engineering Department, Instituto Superior de Engenharia de Lisboa, Instituto
Politécnico de Lisboa, Portugal.
*
Corresponding author. E-mail: luisammartins@tecnico.ulisboa.pt
This work is dedicated to Professor Malcolm Green as a recognition for his outstanding
achievements towards the development of Organometallic Chemistry.
Abstract
3
The C-scorpionate iron(II) complexes [FeCl { -HC(pz) }] (1) (pz = pyrazol-1-yl),
2
3
3
3
Li[FeCl { -SO C(pz) }] (2) and the new [FeCl { -HOCH C(pz) }] (3) act as catalysts for
2
3
3
2
2
3
the hydrocarboxylation of cyclohexane (with CO and H O) to cyclohexanecarboxylic acid in a
2
remarkable yield (up to 60 %) and under mild conditions. The catalysts selectivity for the acid
3
can be tuned by CO pressure, catalyst amount and reaction temperature. Complex [FeCl { -
2
HC(pz) }] (1) provides the most effective catalyst requiring low CO pressure. This work
3
constitutes an unprecedented use of iron complexes as catalysts for the hydrocarboxylation of
alkanes.
1

Keywords: hydrocarboxylation, iron, scorpionate, homogeneous catalysis, aqueous medium,
cyclohexane, carboxylic acid
1
. Introduction
Carboxylations provide industrial core processes to produce both bulk and fine
chemicals, with carbon monoxide being the most important C building block to yield
1
carboxylic acids. However, in view of the drawbacks of the current processes [1-4], alkane
carboxylation towards future sustainable carboxylic acids production appears as a very
promising approach.
Cyclohexane was chosen as model substrate due to the industrial significance of the
carboxylation main product, cyclohexanecarboxylic acid [4,5], used as flavoring agent and as
additive for paint, lubricating and rubber industries.
Carboxylation of cyclohexane to cyclohexanecarboxylic acid (4.3% yield relative to
substrate) was firstly reported [6-8] using a Pd(II) Cu(II) catalyst (TON, moles of product per
/
mole of catalyst, up to 20), CO (2.0 MPa) and peroxodisulfate in trifluoroacetic acid (TFA), at
8
0 °C for 20 h. The strongly acidic medium was needed due to the alkane inertness.
Improvement of cyclohexane carboxylation, namely avoiding the use of TFA, has been
achieved by some of us [9-13], reacting CO, water and peroxodisulfate in water/acetonitrile at
ca. 50 ºC and in the presence of copper [9,10] or gold [11,12] catalytic systems, and affording
up to 88% yield [11] of cyclohexanecarboxylic acid. In these reactions, water acts as a source
1
8
of the hydroxide moiety in the carboxylic acid group (-COOH), as proved by H O
2
experiments, and thus they were named as alkane hydrocarboxylations.[9] To our knowledge,
the current study concerns the first report dealing with hydrocarboxylation of alkanes catalyzed
by iron, although complexes with this metal are known to catalyse alkane carboxylation,
III
0
namely in the Gif systems, of the types Fe trispicolinate/P(OMe) /CO/H O and Fe /CO/O
2
3
2
2
[
14,15]. These earlier catalytic systems operate through a different mechanism from that
followed by the above hydrocarboxylation catalysts (see below).
2

Iron as catalyst is attractive since it is inexpensive, non-toxic and the most abundant
transition-metal. In pursuit of our interest [16-18] on the coordination chemistry of C-
scorpionate
type
hydrotris(pyrazolyl)methanes,
the
neutral
analogues
of
-
hydrotris(pyrazolyl)borates and also isoelectronic with cyclopentadienyl (Cp ) [19], as well as
on the catalytic ability of their metal complexes, herein i) we selected C-functionalized neutral
-
(
HOCH C(pz) ; pz = pyrazol-1-yl) and anionic (SO C(pz) ) tris(pyrazolyl)methanes, as well
2
3
3
3
as their precursor HC(pz) ; ii) studied their coordination behavior at an iron(II) center; and iii)
3
3
n-
compared the catalytic ability of the derived [FeCl { -RC(pz) }] (n = 0, R = H or CH OH; n
2
3
2
=
1, R = SO ) complexes to catalyze the mild hydrocarboxylation of cyclohexane.
3
2
. Experimental section
2
.1. Materials and methods
All operations were carried out in open air, unless stated otherwise. All reagents and
solvents were purchased from commercial sources and used as received, except the solvents for
the synthesis of C-scorpionate complexes, that were dried according to standard procedures.
3
HC(pz) (pz = pyrazoly-1-yl) [20], SO C(pz) [21], HOCH C(pz) [20], [FeCl { -HC(pz) }]
3
3
3
2
3
2
3
3
[
22] and Li[FeCl { -SO C(pz) }] [22] were prepared according to the literature and
2
3
3
characterized accordingly.
IR spectra were recorded on a Bruker Alpha Fourier transform infrared (FT-IR, 4000-
-1
-1
4
00 cm ) spectrometer in KBr pellets. Far infrared spectrum FIR (400–180 cm ) was recorded
1
13
on a Vertex 70 spectrophotometer in CsI pellets. H (300 MHz) and C (75.45 MHz) NMR
spectra were obtained at room temperature on a Bruker 300 MHz spectrometer using
tetramethylsilane [Si(CH ) ] as the internal reference.  values are in ppm and coupling
3
4
constants are in Hz; abbreviations: s = singlet, d = doublet, t = triplet. Elemental analyses were
carried out by the Microanalytical Service of the Instituto Superior Técnico. Electrospray mass
spectra (ESI-MS) were run with an ion-trap instrument (Varian 500-MS LC Ion Trap Mass
Spectrometer) equipped with an electrospray ion source.
GC analyses were performed on a Fisons Instruments GC 8000 series gas
chromatograph with a DB WAX (J&W) capillary column (P/N 122–7032; 30 m×0.25
3

mm×0.25 μm; helium was the carrier gas) and the Jasco-Borwin v.1.50 software. The
attribution of the GC peaks was performed by comparison with the chromatograms of pure
compounds. Quantification was achieved by the internal standard method that consists in
adding a known concentration of a known compound (in this case cycloheptanone) in the
reaction mixture to quantify the components of the sample. In some cases, carboxylation
products were also identified by GC-MS techniques using a Perkin-Elmer Clarus 600 gas
chromatograph, equipped with two capillary columns (SGE BPX5; 30 m x 0.32 mm x 25 mm),
one having an EI-MS (electron impact) detector and the other one with a FID detector. Helium
was used as the carrier gas. Reaction products were identified by comparison of their retention
times with known reference compounds, and by comparing their mass spectra to fragmentation
patterns obtained from the NIST spectral library stored in the computer software of the mass
spectrometer.
3
2
.2 Synthesis of FeCl { -HOCH C(pz) } (3)
2
2
3
To an ethanol (5 mL) solution of FeCl ·2H O (120 mg, 0.74 mmol) was added slowly
2
2
HOCH C(pz) (207 mg, 0.85 mmol) in ethanol (5 mL). A reddish solid precipitated and the
2
3
solution became almost colorless. The solid was filtered off, washed several times with ethanol
-1
and dried under vacuum; yield: 0.16 g (72%). IR ( in cm ): 3366 [m, (OH)], 1617, 1519 and
1
1

3
5
391 [s, (C=C), (N=C) and (N-C)], 361, 315 and 213 [w, (Fe-Cl)]. NMR: H (DMSO-d ),
6
3
8.98 s, 1H, HOCH (pz) , 7.65 d, 3H, J = 2.4, H(3) or H(5), HOCH C(pz) , 7.44 d,
2
3
HH
2
3
3
3
H, J = 2.1, H(5) or H(3), HOCH C(pz) , 6.38 t, 3H, J = 2.3, H(4), HOCH C(pz) ,
HH
2
3
HH
2
3
1
3
1
.87 s, br, 2H, HOCH (pz) . C- H(DMSO-d ,  in ppm, J in Hz),  142.2 s, C(3) and
2
3
6
C(5), HOCH C(pz) , 108.9 s, C(4), HOCH C(pz) , 86.3 s, HOCH C(pz) , 61.8 s,
2
3
2
3
2
3
13
HOCH C(pz) ; C (DMSO-d ,  in ppm, J in Hz),  142.2 [d, J =197.1, C(3) and C(5),
2
3
6
CH
HOCH C(pz) , 108.9
[d, J =183.8, C(4), HOCH C(pz) , 61.8 t, J =193.2,
2
3
CH
2
3
CH
+
+
+
HOCH C(pz) . ESI -MS: m/z 580 ([M-Cl+HOCH C(pz) ] ), 438 (M+pz , 403 (M-
2
3
2
3
+
+
+
+
+
Cl+pz ), 371 (M ), 336 (M-Cl ), 304 (M-pz ), 300 (M-2Cl ). Found: C, 35.94; H, 3.31;
N, 22.21 %. FeCl N OC H requires C, 35.61; H, 3.26; N, 22.65.
2
6
11 12
4

2
.3. Catalytic carboxylation of cyclohexane to cyclohexanecarboxylic acid
In typical experiments, the reaction mixtures were prepared as follows: to 1.0-8.0 μmol
of one of the complexes 1-3 contained in a 13.0ꢀmL stainless steel autoclave, equipped with a
Teflon-coated magnetic stirring bar, 1.50 mmol of K S O , 3.0 mL of H O, 3 mL of MeCN
2
2
8
2
(typical total solvent volume was 6.0 mL) and 1.00 mmol of cyclohexane were added. If used,
the C-radical trap CBrCl was applied in a stoichiometric amount relative to the substrate. Then
3
the autoclave was closed and flushed with N three times to remove the existing air and
2
pressurized with 2-40 atm (typically 2 atm) of CO. The reaction mixture was stirred for 3–10 h
(typically 6 h) at 30–80ꢀ°C (typically 50ꢀ°C) using a magnetic stirrer and an oil bath,
whereupon it was cooled in an ice bath, degassed and the contents were transferred to a
Schlenk flask. Diethyl ether (9.0–11.0 mL) and 90 μL of cycloheptanone (GC internal
standard) were added. The obtained mixture was vigorously stirred for 30 min, and the organic
layer was analyzed typically by GC.
Additional experiments were performed under typical reaction conditions in the
presence of the carbon-centered radical trap CBrCl (used in an equimolar amount relatively to
3
cyclohexane), revealing the full suppression of carboxylic acid formation.
3
. Results and discussion
3
.1. Syntheses and characterization
3
3
Complexes [FeCl { -HC(pz) }] (1) (pz = pyrazol-1-yl), Li[FeCl { -SO C(pz) }] (2)
2
3
2
3
3
3
and [FeCl { -HOCH C(pz) }] (3) were synthesized directly from the metal chloride,
2
2
3
FeCl ·2H O in an alkanol solvent (1 and 3) or water (2), in the presence of the appropriate
2
2
scorpionate,
pyrazolyl)methanesulfonate,
HOCH C(pz) (3) (Scheme 1). Although 1 and 2 were previously prepared [22], complex 3 is
hydrotris(1-pyrazolyl)methane,
HC(pz)3
(1),
lithium
tris(1-
Li[SO C(pz) ]
(2) or
2,2,2-tris(1-pyrazolyl)ethanol,
3
3
2
3
herein obtained and characterized for the first time.
5

FeCl . 2 H O
2
2
HC(pz)3
Li [SO C(pz) ]
HOCH C(pz)
3
3
2
3
1
EtOH, r.t.
H O, r.t.
2
EtOH, r.t.
Li
Cl
Cl
N
N
Cl
Cl
N
N
Cl
Cl
N
N
Fe
CH
Fe
C
SO3
Fe
C
OH
N
N
N
N
N
N
N
N
N
N
N
N
1
2
3
3
3
3
Scheme 1. Synthesis of [FeCl { -HC(pz) }] (1), Li[FeCl { -SO C(pz) }] (2) and [FeCl { -
2
3
2
3
3
2
HOCH C(pz) }] (3) (pz = pyrazol-1-yl).
2
3
All complexes were characterized by IR and NMR spectroscopies, ESI-MS and
elemental analysis. The structural properties of 1 and 2 are in accord with the reported
-1
ones.[22] The IR spectrum of 3 exhibits medium intensity bands in the 3430-3370 cm range,
assigned to (OH) of the ligated HOCH C(pz) [23-26], whereas the (C=C) and (C=N)
2
3
-1
bands of their pyrazolyl groups are observed at the usual range [16] of 1612-1510 cm . The
presence of the chloro ligands is confirmed by the corresponding IR (Fe-Cl) bands at 361, 315
-1
1
and 213 cm . The equivalence of the pyrazolyl groups of 3 in solution is indicated by both H
1
3
and C{1H} NMR spectra which display a single resonance for each type of protons or of
1
3
carbons, i.e. for the 3, 4 or 5 position in the ring. Moreover, in the C NMR spectra a single
+
resonance is observed for the ring carbons at positions 3 and 5. The ESI -MS of 3 exhibits the
+
molecular ion [M] , and the fragmentation pathways occur by cleavage of the Fe-ligand bonds
and rupture of bonds within the 2,2,2-tris(1-pyrazolyl)ethanol ligand. Hence, fragments such as
+
+
[
M-Cl] , [M-2Cl] , and those derived upon further loss of pyrazolyl and chlorines are detected.
Coupling of pyrazolyl or HOCH C(pz) with metal fragments has also been observed, e.g., [M-
2
3
+
+
+
Cl+ HOCH C(pz) ] , [M+pz] and [M-Cl+pz] .
2
3
6

3
.2 Catalytic activity of complexes 1-3 for the hydrocarboxylation of cyclohexane to
cyclohexanecarboxylic acid
The catalytic activity of the C-scorpionate Fe(II) complexes 1–3 for the mild
hydrocarboxylation of C alkanes into C carboxylic acids was tested using cyclohexane
n
n+1
(CyH) as substrate. The reactions were undertaken in stainless steel autoclaves, by reacting, at
typical temperatures of 30-80 ºC and in water/acetonitrile medium, cyclohexane, carbon
monoxide and potassium peroxodisulfate in the presence of 1-3 (Scheme 2). The obtained
results are presented in Table 1.
Scheme 2. Hydrocarboxylation of cyclohexane to cyclohexanecarboxylic acid catalyzed by the C-
scorpionate Fe(II) catalysts 1–3.
Compounds 1-3 were found to exhibit a remarkable catalytic behavior (Table 1) on the
selective production of cyclohexanecarboxylic acid from cyclohexane hydrocarboxylation.
Cyclohexanone was the only byproduct detected and in a low concentration at the optimized
reaction conditions (Table 1). In contrast to previous reported hydrocarboxylations [11,12], no
alcohol (cyclohexanol) was formed by the present iron catalytic systems.
3
Complex [FeCl { -HC(pz) }] (1), bearing the hydrotris(pyrazolyl)methane ligand,
2
3
provides the most effective catalyst leading to carboxylic acid yields up to ca. 59.8% (entry 3,
3
3
Table 1), requiring only 2 atm of CO. Follows Li[FeCl { -SO C(pz) }] (2) and [FeCl { -
2
3
3
2
HOCH C(pz) }] (3) (yields up to 52.8 and 41.9%, entries 13 and 23, respectively, Table 1),
2
3
indicating that the functionalization of hydrotris(pyrazol-1yl)methane, at the apical C with a
sulfonate group or a polar alcohol moiety does not improve the catalytic activity of the Fe(II)
complex for this reaction. Regarding the iron(II) precursor FeCl .2H O, 11.2% of yield was
2
2
obtained (entry 27, Table 1) indicating an important role of the C-scorpionate ligands at the
iron(II) centers. However, the C-scorpionate compounds, by themselves, are not able to
7

catalyze the hydrocarboxylation reaction (see e.g., entry 31 of Table 1 for HC(pz)3).
Experiments in the absence of a catalyst were also performed, at 50 ºC and 20 atm of CO
(entries 28-32, Table 1), yielding, after 6 h, a maximum of 10.3% of cyclohexanecarboxylic
acid (100% selectivity).
a
Table 1. Selected data for the hydrocarboxylation of cyclohexane catalyzed by the C-scorpionate
Fe(II) complexes 1-3.
b
d
Yield of products /%
Selectivity/%
Catalyst
T
Time
/h
P/ atm
e
Entry amount
TON
Cyclohexane
carboxylic
/
ºC
Cyclo-
hexanone
c
/
μmol
Total
acid/ketone
acid
3
[
FeCl { -HC(pz) }] (1)
2
3
4
8
8
8
5
7
4/56
0/20
7/13
5/15
1/49
0/30
1
2
3
4
5
6
7
8
9
1
2
4
8
4
4
4
4
4
4
50
50
50
50
30
80
50
50
50
50
2
2
6
6
9.9
12.6
10.2
8.7
22.5
51.1
68.5
57.4
44.8
48.6
44.1
33.4
52.9
11.0
113
128
86
40.9
59.8
48.8
22.6
34.2
42.4
31.1
42.5
10.4
2
6
2
6
8.6
36
2
6
22.2
14.4
1.7
56
2
6
61
9
6/4
3/7
20
40
2
6
55
9
6
2.3
42
8
0/20
10
3
10.4
0.6
66
9
5/5
1
0
2
14
3
Li[FeCl { -SO C(pz) }] (2)
2
3
3
4
8
5/55
0/20
1
1
1
1
1
1
1
1
1
2
3
4
5
6
7
8
1
2
4
4
4
4
4
4
50
50
50
30
80
50
50
50
2
2
6
6
4.1
5.1
1.4
9.2
45.9
17.7
67.1
56.6
60.6
35.3
18.0
17.7
5.7
7.1
9
8/2
2
6
52.8
31.9
45.7
18.3
13.4
0.9
53.7
45.3
48.6
28.3
14.3
14.2
7
6
1
0/30
2
6
13.4
2.9
9
4/6
2
6
5/35
20
40
2
6
10.0
0.9
9
4/6
6
00/0
10
14.2
0.0
3
[
FeCl { -HOCH C(pz) }] (3)
2
2
3
6
5
5
5
5/35
5/45
0/50
2/48
1
2
2
2
2
2
2
9
0
1
2
3
4
5
1
2
4
4
4
4
4
50
50
50
30
80
50
50
2
2
6
6
6
6
6
6
6
18.9
25.8
25.4
21.2
41.9
39.6
35.4
10.2
21.3
25.9
19.2
2.7
29.1
47.1
51.3
40.4
44.6
41.9
37.9
146
118
64
2
2
50
9
4/6
5/5
3/7
2
56
9
20
40
2.3
52
9
2.5
47
8

6
0/40
2
6
4
50
2
10
30.9
20.4
51.3
64
FeCl .2H O
2
2
5
1
1
1
1
1
6/44
00/0
00/0
00/0
00/0
00/0
2
2
2
3
3
7
8
9
0
1
4
0
0
0
0
8
50
50
50
30
80
50
2
6
6
6
6
6
6
11.2
0.8
0.0
0.0
0.0
0.0
0.0
20.0
2.6
15.0
2
2.6
10.3
2.9
-
-
20
20
20
20
10.3
2.9
-
10.1
10.5
10.1
10.5
-
f
3
2
6.6
a
Typical (unless stated otherwise) reaction conditions: cyclohexane (1.00 mmol), p(CO) = 2 atm,
b
K S O (1.50 mmol), H O (3.0 mL)/MeCN (3.0 mL) in an autoclave (13.0 mL capacity). Product yield
2
2
8
2
c
d
[
%] (moles of product/100 moles of cyclohexane). Cyclohexanecarboxylic acid + cyclohexanone
e
Percentage of each product in the overall products formed. Turnover number (TON) = mol of product
f
per mol of catalyst. Using HC(pz) as catalyst.
3
The effect of CO pressure on the yield of products was investigated for all catalysts, for
the purpose of optimizing the reaction conditions. The amount of carbon monoxide has a
relevant effect on the yield (Figure 1; entries 3, 7 and 8 for 1; entries 13, 16 and 17 for 2 and
entries 21, 24 and 25 for 3, Table 1) which gradually decreases with the CO pressure increase
up to 40 atm, at constant temperature (50 ºC), conceivably due to the deactivation of the
catalyst as a result of the formation of carbonyl complexes. In fact, the coordination
polyhedron of all C-scorpionate Fe(II) complexes 1-3 is a tetragonal pyramid (Scheme 1).
Thus, the iron atom has one empty coordination site that can be occupied by CO, what is
promoted by an increase in its pressure. Among the tested conditions, 2 atm of CO led to the
best hydrocarboxylation yields (e.g., in the presence of 1, an increase of the CO pressure from
2
to 20 and 40 atm results in a total yield drop from 68.5 to 44.1 and 37.9%, respectively), 10
times less than the required pressure for the reaction to occur appreciably in the absence of a
metal catalyst and leading to a 6 times higher yield of cyclohexanecarboxylic acid.
9

Figure 1. Effect of CO pressure on the total yield (cyclohexanecarboxylic acid and cyclohexanone)
in the system catalyzed by complexes 1-3 for the hydrocarboxylation of cyclohexane. Reaction conditions:
cyclohexane (0.5 mmol), catalyst (4 mol) 50 ºC, 6 h, in H O/MeCN.
2
An increase on the catalyst amount results in a total yield enhancement, e.g., for 1, from
2
2.5 to 68.5% upon changing the amount of catalyst from 1 to 4 mol (Figure 2; Table 1,
entries 1 to 3). The use of higher amounts of catalyst (e.g., 8 mol) does not appear to improve
the reaction throughput. In fact, although the cyclohexanone yield was maintained, a yield drop
for cyclohexanecarboxylic acid was observed (Figure 2; Table 1, entry 4). As expected, rising
the catalyst amount results in a corresponding decrease of TON (moles of product/moles of
catalyst) values (Table 1).
1
0

Figure 2. Dependence of cyclohexanecarboxylic acid and cyclohexanone yields on the amount of
3
[
FeCl { -HC(pz) }] (1). Reaction conditions: cyclohexane (0.5 mmol), 1-8 mol of 1, CO (2 atm), 6 h and
2
3
at 50 ºC in H O/MeCN.
2
Moreover, for 1 and 2, the increase of the catalyst amount led to higher selectivities to
3
the carboxylic acid formation. [FeCl { -HOCH C(pz) }] (3) did not follow such a behavior,
2
2
3
requiring also an increase on the CO pressure or on the reaction temperature to form selectively
the cyclohexane carboxylic acid (compare entries 21, 23 and 24, Table 1).
In this catalytic system the temperature has a major effect not only on the yield of the
carboxylation products but also in the selectivity. Thus, for all catalysts, it can be seen (Figure
3
) that when a lower temperature of 30 °C is used, not only a lower amount of cyclohexane
carboxylic acid and cyclohexanone is formed but also a lower selectivity is observed. For
example, in the presence of 1, a selectivity for cyclohexanecarboxylic acid [moles of acid/(100
moles of acid + ketone)] of 51, 87 and 70% is observed when the reaction is performed at 30,
5
0 and 80 ºC, respectively Figure 3a, Table 1).
1
1

(a)
(b)
(c)
Figure 3. Influence of temperature on the hydrocarboxylation products (cyclohexanecarboxylic acid
and cyclohexanone) of cyclohexane catalyzed by 1 (a), 2 (b) or 3 (c). Reaction conditions: cyclohexane (0.5
mmol), catalyst (4 mol), CO (2 atm), 6 h, in H O/MeCN.
2
In addition, the yield values of the present work are comparable to those reported
earlier for the efficient Cu-catalyzed hydrocarboxylations of cyclohexane in H O/MeCN
2
medium [27].
III
The abovementioned Gif catalytic systems for alkane carboxylation, Fe
0
trispicolinate/P(OMe) /CO/H O and Fe /CO/O , have a low activity, leading to yields of only
3
2
2
2
5
% and 0.03% respectively. [14,15]
According to previous studies [9-11] and experimental data (full suppression of
carboxylic acid formation for the reaction performed in the presence of the carbon-centered
radical trap CBrCl ), the hydrocarboxylation of cyclohexane is proposed to proceed via a free-
3
radical mechanism (Scheme 3) that involves the following main steps: i) formation of the
•−
cyclohexyl radical generated by H abstraction from cyclohexane by the sulfate radical SO4
produced by thermolysis of K S O ; ii) formation of the acyl radical from reaction of
2
2
8
cyclohexyl radical with CO; iii) oxidation of the acyl radical by Fe(III) species (previously
oxidized by K S O ) to the acyl cation and hydrolysis of the acyl cation to yield the
2
2
8
cyclohexanecarboxylic acid (metal assisted route a). Alternatively, a metal-free pathway (b)
2
-
can also operate, where the acyl radical is oxidized by S O .
2
8
This proposed mechanism, of a radical nature, is quite different from that suggested for
the abovementioned alkane carboxylation Gif systems, that do not operate via carbon radicals
[
14,15] and for which the hydroxylating role of water was not shown.
1
2

Scheme 3. Proposed simplified mechanism for the hydrocarboxylation of cyclohexane [9-11].
The cyclohexanone by-product is formed by a competing side reaction: oxidation
2
−
(
instead of hydrocarboxylation) of cyclohexane. The oxidizing agents are S O8 and O , and
2 2
the reaction is expected to occur via a radical mechanism, as reported previously [16,18,22] in
other cyclohexane oxidation reactions catalyzed by C-scorpionate iron complexes. The
.
cyclohexyl radical (Cy ), formed upon H abstraction from cyclohexane by the sulfate radical
•−
SO4 (produced by thermolysis of K S O ), undergoes fast reaction with O to form the
2
2
8
2
.
peroxyl radical (CyOO ), which decomposes to form cyclohexanone.
The formation of cyclohexanol is also expected to occur by the usual radical pathways
16,18,22]. However, in our case, the chosen catalyst, which also efficiently catalyzes [28,29]
[
the oxidation of alcohols, promotes the further oxidation of the formed cyclohexanol to the
only detected by-product, the cyclohexanone.
1
3

4
. Conclusions
In this work, the ability of Fe complexes to effectively catalyze the hydrocarboxylation
of alkanes has been proved. Moreover, the hydrocarboxylation can be performed under mild
conditions. In fact, the iron(II) scorpionate complexes [FeCl {HC(pz) }] (1) (pz = pyrazol-1-
2
3
yl), [FeCl {SO C(pz) }] (2) and the new [FeCl {HOCH C(pz) }] (3) act as active and selective
2
3
3
2
2
3
catalysts (total yields, after 6 h, up to 69% in the case of 1, selectivity for
cyclohexanecarboxylic acid up to 98%, in the case of 2) for the hydrocarboxylation of
cyclohexane, in the presence of carbon monoxide (2 atm), potassium peroxodisulfate in
aqueous/acetonitrile medium at a very mild temperature (50 ºC).
Therefore, this study contributes towards the development of more sustainable catalytic
synthetic protocols for the hydrocarboxylation of C alkanes into Cn+1 carboxylic acids, using
n
simple and inexpensive starting materials, and focusing on an abundant and environmentally
tolerable metal (iron).
Acknowledgments
Funding from FCT (Fundação para a Ciência e a Tecnologia, Portugal)
(UID/QUI/00100/2019, PTDC/QEQ-ERQ/1648/2014 and PTDC/QEQ-QIN/3967/2014
projects) are acknowledged.
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[
1
6




Homogeneous C-scorpionate Fe(II) complex catalyze cyclohexane hydrocarboxylation
Water acts as a source of the hydroxide moiety in the carboxylic acid group
Cyclohexanecarboxylic acid is selectively produced in good yield
1
7