Catalytic oxidation of alcohols with novel non-heme N4-tetradentate manganese(ii) complexes

Article abstract of DOI:10.1039/c8dt03808b

We report the preparation and characterisation of a series of novel non-heme N₄-tetradentate Mn(OTf)₂ complexes of the type, [(L)MnOTf₂], where L = R,R and S,S enantiomers of BPMCN, its 6-methyl and 6-bromo derivatives as well as the novel ligand BMIMCN (BPMCN = N,N′-dimethyl-N,N′-bis(2-pyridylmethyl)-(R,R/S,S)-1,2-diaminocyclohexane, BMIMCN = N,N′-dimethyl-N,N′-bis(1-methyl-2-imidazolemethyl)-(R,R/S,S)-1,2-diaminocyclohexane). Solid state structural analysis of the BMIMCN-ligated Mn-triflate complexes (R,R-C4 and S,S-C4) revealed opposite helicity but identical metal site accessibility. This feature was exploited in the catalytic oxidation of primary and secondary alcohols, with hydrogen peroxide as oxidant and acetic acid as co-catalyst. Complexes R,R-C4 and S,S-C4 displayed the highest activity in benzyl alcohol oxidation, attributed to the electron-donating property of the BMIMCN ligand. Complex S,S-C4, displayed high activity for a variety of primary alcohol substrates, but the reaction suffered from reduced selectivity and side-reactions due to the presence of acetic acid. In contrast, secondary alcohol substrates could be oxidised to the corresponding ketone products in excellent isolated yields under mild reaction conditions and short reaction times.

Full text of DOI:10.1039/c8dt03808b

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Catalytic oxidation of alcohols with novel non-
heme N4-tetradentate manganese(II) complexes†
Cite this: Dalton Trans., 2018, 47,
16534
Vincent Vermaak,
Desmond A. Young and Andrew J. Swarts
*
We report the preparation and characterisation of a series of novel non-heme N4-tetradentate Mn(OTf)2
complexes of the type, [(L)MnOTf2], where L = R,R and S,S enantiomers of BPMCN, its 6-methyl and
6-bromo derivatives as well as the novel ligand BMIMCN (BPMCN = N,N’-dimethyl-N,N’-bis(2-pyridyl-
methyl)-(R,R/S,S)-1,2-diaminocyclohexane, BMIMCN
= N,N’-dimethyl-N,N’-bis(1-methyl-2-imidazole-
methyl)-(R,R/S,S)-1,2-diaminocyclohexane). Solid state structural analysis of the BMIMCN-ligated Mn-
triflate complexes (R,R-C4 and S,S-C4) revealed opposite helicity but identical metal site accessibility.
This feature was exploited in the catalytic oxidation of primary and secondary alcohols, with hydrogen
peroxide as oxidant and acetic acid as co-catalyst. Complexes R,R-C4 and S,S-C4 displayed the highest
activity in benzyl alcohol oxidation, attributed to the electron-donating property of the BMIMCN ligand.
Complex S,S-C4, displayed high activity for a variety of primary alcohol substrates, but the reaction
suffered from reduced selectivity and side-reactions due to the presence of acetic acid. In contrast, sec-
ondary alcohol substrates could be oxidised to the corresponding ketone products in excellent isolated
yields under mild reaction conditions and short reaction times.
Received 20th September 2018,
Accepted 31st October 2018
DOI: 10.1039/c8dt03808b
rsc.li/dalton
to their Fe(II)-counterparts.13,15,16 The only drawback is the
necessity of an excess co-catalyst,7,9,17 particularly a carboxylic
Introduction
The production of carbonyl compounds, i.e. aldehydes and acid such as acetic acid (AcOH), to facilitate catalyst acti-
ketones, has become an important research field in recent vation13 and suppress the disproportionation of H2O2.9
years due to their use in the pharmaceutical and perfume Although catalytic oxidation studies of alkanes and alkenes have
industry.1,2 Although several effective processes have been uti- been numerous, the catalytic oxidation of alcohols with non-
lised to produce them via the oxidation of alcohols, it requires heme Mn(II)-complexes has received little attention.3,11,17,18,19,20
the use of hazardous oxidisers (HNO3, KMnO4 and CrO3)3,4 In general, the reported activity and selectivity in alcohol oxi-
and expensive metals (Au, Pt and Cr).5,6 A greener alternative dation is low, facilitating a need for Mn(II)-complexes capable of
which utilises more benign conditions (lower temperatures catalysing alcohol oxidation with high activity and selectivity.
and pressures), a cheaper metal (Mn) and an environmentally Herein, we report our contribution to the development of novel
friendly oxidant (H2O2) has been found in the form of non- non-heme N4-tetradentate Mn(OTf)2 complexes, derived from the
heme manganese(II) complexes. The catalytic oxidation of R,R and S,S enantiomers of BPMCN and its 6-substituted deriva-
hydrocarbons with non-heme Mn(II)-complexes has received tives (R,R-C1–C3 and S,S-C1–C3, Scheme 1) as well as the novel
significant attention in the last few decades and has proved to BMIMCN ligand (R,R-C4 and S,S-C4, Scheme 1). Catalyst and
show high activity, selectivity and versatility towards various reaction parameter optimisation was accomplished with benzyl
alkane and alkene substrates.7–14 Classic N4-tetradentate alcohol (BnOH) as substrate, with H2O2 and AcOH serving as the
ligands which have been employed include TMTACN, BPMCN, oxidant and co-catalyst, respectively. Finally, the most active pre-
BQEN and TPA, with variations including the type of backbone catalysts, R,R-C4 and S,S-C4, were evaluated against a variety of
and substituents on the heterocyclic ring. Advantages of using primary and secondary alcohol substrates, thereby establishing
Mn(II)-complexes, is that they display higher activity compared the substrate scope of our catalyst system.
Research Focus Area for Chemical Resource Beneficiation, Catalysis & Synthesis
Experimental
General considerations
Group, North-West University, 11 Hofmann Street, Potchefstroom, 2531, South
Africa. E-mail: andrew.swarts@nwu.ac.za
†Electronic supplementary information (ESI) available. CCDC 1864576 and
All chemicals and reagents were obtained from commercial
sources and used as received. Catalytic experiments were con-
1864577. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c8dt03808b
16534 | Dalton Trans., 2018, 47, 16534–16542
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5.082 mmol) and glacial acetic acid (0.75 ml) was added to the
solution. The solution was stirred for 30 min after which
NaBH4 (73 mg, 1.923 mmol) was added portion wise. The reac-
tion mixture was stirred for 72 hours at ambient temperature
where after the MeCN was removed in vacuo. KOH (2 M) was
added to the oily residue to raise the pH of the solution above
10. The resulting aqueous solution was extracted with DCM
(3 × 10 ml portions), separated and the organic layer washed
with H2O (2 × 10 ml portions) and saturated NaCl solution (1 ×
10 ml portion). The organic layer was dried over Na2SO4 and
the solvent removed in vacuo to obtain a brown oil (114 mg;
77%). FT-IR (ATR, ν, cm−1): 3050, 2930, 2856, 2791, 1591, 1433,
1264, 732. 1H NMR (600 MHz, CDCl3, ppm) δ: 8.51 (d, J =
4.8 Hz, 2H), 7.60 (dd, J = 6.2, 1.6 Hz, 2H), 7.16–7.11 (m, 2H),
3.94 (d, J = 14.5 Hz, 2H), 3.82 (d, J = 14.6 Hz, 2H), 2.30 (s, 6H),
2.00 (dd, J = 10.6, 2.3 Hz, 2H), 1.85–1.70 (m, 2H), 1.34–1.27 (m,
2H), 1.23–1.12 (m, 2H). 13C NMR (151 MHz, CDCl3, ppm)
δ: 161.29, 148.63, 136.32, 122.92, 121.63, 64.53, 60.44, 36.68,
30.96, 25.84, 25.82. Experimental procedures for the prepa-
ration of R,R and S,S-L1–L4 provided in the ESI.†
Scheme 1 Synthesis of Mn(II)-triflate complexes, R,R-C1–C4. Complexes
S,S-C1–C4 prepared in an analogous fashion from the S,S-enantiomers.
ducted with 30% H2O2, containing an inhibitor to prevent dispro-
portionation, and stored in a refrigerator when not in use. FT-IR
spectra were recorded as neat samples on a BrukerAlpha-P range
infrared spectrometer equipped with an ATR accessory in the
range 400 cm−1 to 4000 cm−1. GC and GC-MS analysis were both
performed on an Agilent 6890 Series GC System equipped with a
HP-5 column: 30 m × 0.320 mm × 0.25 mm. Rinsing solutions
included MeCN (GC) or MeOH and DCM (GC-MS) with N2 (GC)
or He (GC-MS) serving as the carrier gas and biphenyl as an
Synthesis of [(R,R-L1)Mn(II)(OTf)2], R,R-C1
To a stirring solution of Mn(OTf)2 (165 mg, 0.443 mmol) in di-
chloromethane (2 ml) was added R,R-L1 (155 mg, 0.478 mmol)
in dichloromethane (2 ml). The reaction mixture was stirred
for 1 hour. After the allotted time, the pale yellow solution was
filtered to remove metallic manganese, the solvent reduced
and Et2O added. The pale-yellow/beige solid which formed was
washed with Et2O (2 × 20 ml portions), dried in vacuo to afford
a beige solid (146 mg, 46%). UV/vis, nm (ε, A/mol dm−3):
210.5 (3463), 263.5 (4082). Anal. calc. (found) for
MnC22N4O6H28F6S2: C 38.99 (39.53); H 4.17 (3.84); N 8.27
(8.47); S 9.47 (9.14). μeff = 5.553 BM (297 K, MeCN). APCI-MS
(m/z): 528.1214 [M − OTf]+. Experimental procedures for the
preparation of R,R-C2–C4 and S,S-C1–C4 provided in the ESI.†
1
internal standard. H and 13C {1H} NMR spectra were recorded
on a Bruker Ultrashield Plus (600 MHz and 151 MHz, respect-
ively) in 5 mm cylindrical glass tubes. Magnetic susceptibility
measurements were conducted using a Sherwood Scientific MK1
with sample tubes (4 mm diameter) containing 50 mM samples
in acetonitrile. UV-vis spectroscopic analysis was performed on a
Specord® s600 (AnalyticJena) at 298 K in 10 mm quartz cuvettes.
Elemental analysis was carried out by the University of KwaZulu-
Natal (UKZN) Mass Spectrometry Laboratory and the North-West
University (NWU) Potchefstroom Laboratory for Analytical
Services on a PerkinElmer 2400 Series II CHNS-O elemental
analyser. Melting point analysis was performed on a Buchi
Melting Point B-540. Catalytic reaction products were identified
and characterised by GC and GC-MS while the isolated secondary
X-ray crystal analysis
Single crystals of complexes R,R-C4 and S,S-C4 were mounted
on a nylon loop and centred in a stream of cold nitrogen at
173(2) and 200(2) K respectively. Crystal evaluation and data
collection were performed on a Bruker D8 Quest Eco diffract-
ometer with Mo Kα radiation (λ = 0.71073 Å). Data collection,
reduction and refinement were performed using SAINT24 and
SADABS,25 which forms part of the APEX3 software package.26
The structures were solved by direct methods and refined by
full-matrix least-squares on F2 using SHELX-201627 within the
X-Seed graphic user interface.28,29 All non-hydrogen atoms
were refined anisotropically and all hydrogen atoms were
placed using calculated positions and riding models.
1
alcohol oxidation products were confirmed with FT-IR, H and
13C {1H} NMR spectroscopy after isolation.
Non-heme N4-tetradentate ligands, R,R-L1–L4 and S,S-L1–L4
and Mn(OTf)2, R,R and S,S-C1–C4, complex synthesis
Resolution of the 1,2-diaminocyclohexane tartrate salt,
synthesis of the non-heme N4-tetradentate ligands and their
Mn(OTf)2 complexes was done using previously reported litera-
ture procedures.10,21–23
Screening of complexes in benzyl alcohol oxidation
The Mn(II)-complex (2 μmol) was dissolved in MeCN (1.225 ml)
along with BnOH (2 mmol) and AcOH (10 equivalents,
1.140 ml). Following dissolution, 4 equivalents (0.620 ml) of
Synthesis of N,N′-dimethyl-N,N′-bis(2-pyridylmethyl)-(R,R)-
1,2-diaminocyclohexane (R,R-BPMCN) (R,R-L1)
R,R-BPMCN-amine (136 mg, 0.4587 mmol) was dissolved in 30% H2O2 was added by syringe pump over a period of
MeCN (5 ml). Whilst stirring, 35% formaldehyde (436 mg, 30 minutes where after the reaction was stirred for an
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additional
5
minutes. Final concentrations: complex corresponding to [M − OTf]+, a common feature of these and
(0.620 mM), BnOH (620 mM), AcOH (6.2 M) and H2O2 (2.5 M) analogous manganese(II)-triflate complexes.8,9,20 Magnetic
The mixture was filtered through a silica plug and analysed by susceptibility values (μeff), recorded in acetonitrile solvent, were
GC employing biphenyl as an internal standard. All catalytic in the range 5.6–5.9 BM for both R,R and S,S configurations.
runs were done in duplicate and are reported as the average of The experimentally obtained values are in the range observed
these independent runs. Additional experimental details are for previously reported Mn(II) complexes.9,10,30 Finally, elemen-
provided in the ESI.†
tal analysis confirmed the bulk purity of the isolated complexes.
The solid state structures of R,R-C4 and S,S-C4 were unam-
biguously established by X-ray analysis. Suitable crystals were
grown by slow diffusion of diethyl ether into concentrated
acetonitrile solutions of the complexes. The ellipsoid diagrams
for R,R-C4 and S,S-C4 are shown in Fig. 1a and b respectively,
Results and discussion
Ligand and complex synthesis
The N4-tetradendate ligands, R,R-L1–L4 and S,S-L1–L4, were while crystallographic data and selected bond lengths and
prepared according to a reductive amination of the conden- angles appear in Tables S2 and S3.† For both complexes, the
sation products formed between various carboxaldehydes and coordination geometry about the metal centre is distorted
R,R or S,S-1,2-diaminocyclohexane tartrate salt (ESI, octahedral in which the respective ligands adopt a cis-α topo-
Scheme S1†). The ligands (R,R-L1–L4 and S,S-L1–L4) were iso- logy. Complexes R,R-C4 and S,S-C4 are enantiomers of each
lated as yellow or brown oils in good to excellent yields. All the other in the solid state, crystallising in the enantiomeric space
prepared ligands displayed solubility in polar protic and groups P41212 and P43212 respectively. In the case of R,R-C4
aprotic organic solvent and were insoluble in non-polar this results in a Δ helical chirality of the complex, whereas in
organic solvents and water. Spectroscopic characterisation by the case of S,S-C4 it results in a Λ helical chirality of the
FT-IR and NMR spectroscopy confirmed the formation of the complex. In both instances the nitrogen atoms of the
desired ligands. Finally, R,R-L1–L2 and S,S-L1–L2 (BPMCN N-methylimidazole moieties (N1 and N1′) are situated trans to
and BMPMCN) have been reported previously,12 whereas R,R- each other, whereas the aliphatic nitrogen atoms (N3 and N3′)
L3–L4 and S,S-L3–L4 (BBPCM and BMIMCN) are novel.
are situated cis to each other. A comparison of the Mn–N bond
The Mn(II)-triflate complexes, R,R-C1–C4 and S,S-C1–C4, lengths reflect the different chemical nature of the donor
were prepared by reacting Mn(OTf)2 with a slight excess of the atoms. In both cases, the Mn–N1 bond lengths are signifi-
corresponding ligand (Scheme 1 and Fig. S1†).
cantly shorter [∼2.143(6) Å] than the corresponding Mn–N3
The desired complexes were isolated, after reaction work- bond lengths [∼2.373(6) Å].
up, as pale-yellow/white or beige solids in moderate yields
In general, the Mn–N distances for complexes R,R-C4 and
ranging between 46–74% (see ESI†). Complexes R,R-C1–C4 and S,S-C4 are in the range observed for analogous high spin
S,S-C1–C4 were found to be fairly stable in air (up to one week) Mn(II) complexes with N4-tetradentate ligands reported in
and displayed solubility in polar organic solvents while being literature.10,31–35 As expected, comparative space-filling struc-
insoluble in ethers and alkanes. The complexes were character- tural analysis shows the same degree of accessibility of the
ised by a range of spectroscopic and analytical techniques. binding sites (represented by the triflate O-atoms) to the bulk
Analysis by APCI-MS showed characteristic mass fragments (Fig. 2a and b). This observation suggests that, all other factors
Fig. 1 Ellipsoid diagrams of (a) R,R-C4 and (b) S,S-C4 drawn at 50% probability.
16536 | Dalton Trans., 2018, 47, 16534–16542
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Fig. 2 Space-filling diagrams of (a) R,R-C4 and (b) S,S-C4. The trifluoromethanesulfonate groups and hydrogen atoms have been omitted for
clarity, but the O-atoms directly bound to the manganese centre have been retained. Colour code: grey (C), turquoise (Mn), blue (N) and red (O).
being equal, both R,R-C4 and S,S-C4 should display similar version of benzyl alcohol to benzaldehyde, confirming the
catalytic activity.
importance of using a ligated Mn(II) complex (Table 1, entry 7)
and AcOH as co-catalyst. No significant increase in conversion
was seen when the oxidant concentration was increased
(Table 1, entries 8 and 12).
Mn(II)-Catalysed benzyl alcohol oxidation
A series of control experiments were conducted prior to screen-
ing the complexes, R,R-C1–C4 and S,S-C1–C4 in benzyl alcohol
oxidation. Performing the oxidation reaction in the presence
Screening of complexes in benzyl alcohol oxidation
and absence of a manganese(II) salt, Mn(OTf)2 or MnCl2·4H2O, To evaluate the effect of ligand substituents and N-donors on
with 1.2 equivalents of hydrogen peroxide as oxidant showed activity, the complexes were subjected to oxidation of benzyl
no catalytic activity (Table 1, entries 1–3). The addition of 10 alcohol (BnOH) with H2O2 serving as the oxidant along with
equivalents of AcOH as co-catalyst in the presence of Mn(OTf)2 AcOH as co-catalyst (Scheme 2). Low conversions not exceed-
(Table 1, entry 4) or MnCl2·4H2O (Table 1, entry 5) resulted in ing 30% were observed for all the complexes (Fig. 3). The chir-
no improvement in conversion. These results established that ality of the complexes tested did not have any significant effect
the metal precursor, in the absence of ligand, or the oxidant on conversion which is attributed to the occurrence of
on its own does not catalyse the oxidation reaction.
dynamic interchangeability between different ligand topolo-
Employing complex R,R-C1 as catalyst, in the absence of gies (cis-α and cis-β) in solution, and the fact that the product
acetic acid, resulted in no conversion (Table 1, entry 6). On the formed is achiral. In addition, solid state structural analysis
other hand, the inclusion of acetic acid resulted in 19% con- confirms that the active site accessibility is the same in both
Table 1 Preliminary screening conditions for benzyl alcohol oxidation
Entry
Catalyst (mol%)
H2O2 (equivalents)
AcOH (equivalents)
Conversiona (%)
Aldehyde selectivity (%)
1
2
3
4
5
6
7
8
—
1.2
1.2
1.2
1.2
1.2
1.2
1.2
4.0
—
—
—
10
10
—
10
10
0.0
0.0
0.0
0.0
0.0
0.0
18.6
20.6
—
—
—
—
—
—
92
93
0.1 (Mn(OTf)2)
0.1 (MnCl2·4H2O)
0.1 (Mn(OTf)2)
0.1 (MnCl2·4H2O)
0.1 (R,R-C1)
0.1 (R,R-C1)
0.1 (R,R-C1)
Reaction conditions: A manganese salt or R,R-C1 (2 µmol) was dissolved in acetonitrile with benzyl alcohol (2 mmol) and AcOH (0 or 1.140 ml).
H2O2 (0.19 or 0.620 ml) was added by syringe pump over 30 min at 25 °C (total volume = 3.19 ml) and stirred for an additional 5 min.
a Conversions and aldehyde selectivity was determined by GC against an internal standard (biphenyl).
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Scheme 2 General procedure used for screening Mn(II)-complexes
against benzyl alcohol oxidation.
Fig. 4 Optimisation of catalyst concentration. Reaction conditions:
Complex S,S-C4 (0.1–1 mol%) in acetonitrile (1.225 ml) with BnOH
(0.8 mmol), AcOH (8 mmol) and H2O2 (3.2 mmol) at 298 K for 35 min.
All values are the average of a duplicate set of runs.
Fig. 3 Screening of Mn(II)-complexes R,R-C1–C4 and S,S-C1–C4.
Reaction conditions: A complex (0.1 mol%) was dissolved in acetonitrile
(1.225 ml) with BnOH (2 mmol), AcOH (20 mmol) and H2O2 (8 mmol) at
298 K for 35 min.
centage conversion of benzyl alcohol with a concomitant
decrease in benzaldehyde selectivity due to over-oxidation
(Fig. 4, ESI, Fig. S2 and S3†).3 In addition, increasing H2O2
and AcOH concentrations above 2 equivalents had no ben-
eficial effect on activity, likely due to active site saturation.38
configurations, which would preclude any differential effect on
activity.
Catalytic oxidation of primary alcohols
Higher benzyl alcohol conversions were observed for com-
plexes C1 and C4 (both R,R and S,S configurations) compared
to those which had methyl- (C2) and bromo-substituents (C3)
on the C6 position of the pyridine donor. This is due to the
substituents exerting a stronger steric rather than electronic
effect during the reaction and substituents in the 6-position
resulting in an elongation of the Mn–Npyridine bond.12 This
elongation leads to a reduction in the thermodynamic stability
of the active catalyst and potential demetallation.36 No signifi-
cant difference emerged when the methyl and bromo substi-
tuted complexes were compared to each other. The higher con-
versions for complex C4 compared to complex C1 can be attrib-
uted to its higher basicity (higher pKa value) resulting in a
stronger electron donor.37 This is advantageous to the stabilis-
ation of high valent manganese intermediate species and in
doing so increases its lifetime.16 The higher conversion may
also be attributed to a more facile approach of substrate to the
sterically accessible catalytic centre in complex C4 compared
to the bulkier C1.
After optimisation of reaction parameters, the following reac-
tion conditions were chosen to achieve high conversion but
minimize over-oxidation: 0.5 mol% S,S-C4, 4 equivalents of
H2O2 and 10 equivalents of AcOH. Under these conditions,
various primary alcohol substrates were evaluated to establish
the scope of Mn(II)-catalysed alcohol oxidation (Table 2). The
addition of electron-donating groups on the benzene ring, i.e.
amino (Table 2, entry 2), methoxy (Table 2, entry 3), resulted
in increased conversion.17 A drawback was the formation of
dimers from 2-aminobenzaldehyde as soon as it formed due to
self-condensation in the presence of a Mn(II)-complex and
dilute acidic solutions.39 Insertion of a para-hydroxy group
(Table 2, entry 4) resulted in a low conversion due to its lack of
solubility in MeCN, while the addition of an iodine group
(Table 2, entry 5) on the ortho-position decreased the conver-
sion, again illustrating the influence that steric pressure has
on catalytic activity. Increasing the aliphatic chain length by
employing 3-phenyl-1-propanol as substrate led to a 20%
increase in conversion, albeit with over-oxidation to the car-
boxylic acid (Table 2, entries 6 vs. entry 1). In contrast, employ-
ing 2-phenylethanol as substrate decreased the conversion
Optimisation of reaction parameters
After screening of the different complexes, complex S,S-C4 was (Table 2, entry 7 vs. entry 1). The α and β carbons in the
chosen for further optimisation of reaction parameters, i.e. alcohol are both activated which under catalytic conditions
catalyst, AcOH and H2O2 concentrations. From preliminary can generate α-ketoaldehydes or α-ketocarboxylic acids as pro-
studies, it was determined that temperature variation (−5 °C to ducts. These have the potential to ligate to the metal, resulting
25 °C) and reaction time (35 min to 190 min) had no beneficial in competitive inhibition and a decrease in conversion.40 Over-
effect on the oxidation of benzyl alcohol (ESI, Table S1†). The oxidation towards the carboxylic acid resulted in an esterifica-
latter observation may be attributed to catalyst decomposition. tion reaction with the alcohol substrate to produce phenethyl
The observed effect of variations in catalyst, H2O2 and AcOH phenylacetate as the product.
concentrations was found to be similar. An increase in the
Evaluation of cinnamyl alcohol (Table 2, entry 8) resulted in
concentration of each parameter led to an increase in the per- the epoxide as major product rather than an aldehyde or car-
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Table 2 Catalytic oxidation of primary alcohols with S,S-C4 a
Entry
1
Substrate
Major product
Conversionb/%
47
TONc
97
Aldehyde selectivity (%)
79
2
3
4
5
77
69
22
22
155
140
45
55
80
74
96
45
6
7
8
9
67
38
82
51
134
76
13
43
22
94
170
105
10
97
195
57
11
12
80
72
163
149
11
5
a Reaction conditions: Complex S,S-C4 (0.5 mol%) in acetonitrile with alcohol (0.8 mmol), AcOH (8 mmol) and H2O2 (3.2 mmol) at 298 K for
35 min. b Conversions were determined by GC against an internal standard (biphenyl). c Turnover number (TON) = mol substrate converted per
mol complex used.
boxylic acid which is attributed to the higher reactivity of non- sion. This is in contrast to previous studies where benzylic
heme Mn(II)-complexes towards alkene oxidation compared to alcohols were more reactive than their aliphatic counter-
alcohol oxidation.41 Insertion of a heteroatom into the phenyl parts.40,43 Both cyclohexanemethanol and 1-octanol, however,
ring had no significant effect on the conversion compared to over-oxidises to the carboxylic acid but contrary to a previous
benzyl alcohol (Table 2, entry 9 vs. entry 1). In contrast, a sig- study, a higher percentage 1-octanol was converted in our
nificant increase in conversion was observed when a furan study using a lower substrate concentration and much shorter
ring was used as the heterocycle due to the increased reactivity reaction time.18
of furan (Table 2, entry 10). Another problem was the rapid
decomposition of furfural in the presence of an acid, tran-
Catalytic oxidation of secondary alcohols
sition metal and H2O2 which explains the high percentage con- Due to the selectivity problems encountered during the oxi-
version.42 Maleic anhydride was observed as one of the dation of primary alcohols, it was decided to extend the study
decomposition products. High catalytic activity towards the towards secondary alcohol substrates (Table 3). The oxidation
oxidation of cyclic and linear aliphatic primary alcohols was of 2-octanol and 4-phenyl-2-butanol (Table 3, entries 1 and 2)
observed, in which 80% of the cyclohexanemethanol (Table 2, were conducted with both S,S-C4 and R,R-C4 as catalysts with
entry 11) and 72% of the 1-octanol (Table 2, entry 12) was con- identical results being obtained, providing further evidence
verted. Removing the aromaticity from the ring increases the that the configuration and ultimately topology of the complex
electron density at the α-carbon resulting in a higher conver- does not have an effect during alcohol oxidation. In general,
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Table 3 Catalytic oxidation of secondary alcoholsa
yields were obtained for the cyclic ketones due to a higher dis-
tribution of the ketones in the water phase compared to the
organic phase and high volatility.43 Other solvents, i.e. CHCl3
and Et2O, were also utilised for extraction and salting out
methods were employed but no improvement was seen.
Finally, a bicyclic aliphatic alcohol, i.e. isoborneol, was also
oxidized in near quantitative conversion and 86% isolated
yield (Table 3, entry 8). In the context of manganese(II)-cata-
lysed secondary oxidation, the reported catalytic activity (con-
versions and isolated yields) for the substrates in Table 3 are
comparable and in some cases better than literature pre-
cedent. Bhat et al. reported a Mn(II)/terpyridine-ligated com-
plexes, which with a catalyst concentration of 0.5 mol% was
capable of oxidising 2-phenylethanol and cyclohexanol to the
corresponding ketone in 11% and 38% GC yield respectively
vs. 10% and 84% isolated yield when employing our catalyst
system.44 Gao and co-workers reported a porphyrin-inspired
Mn(II) complex which operated as an alcohol oxidation catalyst
at a catalyst concentration of 1 mol%. Operating under these
conditions cyclohexanol and 2-octanol was oxidised to the
ketones in 38% and 25% GC yield respectively. In comparison
isolated yields of 10% and 51% were obtained for these sub-
strates when employing our catalyst system.45 Nam, Sun and
co-workers evaluated non-heme Mn(II) complexes, operating at
catalyst concentrations of 0.3 mol%, in the oxidation of sec-
ondary alcohols.46 Under these conditions 2-phenylethanol
and cyclohexanol were oxidised to the ketones in 93% and
86% isolated yield respectively. This example is the most
efficient Mn(II) catalyst for alcohol oxidation reported to date.
Our catalyst system also outperforms analogous Fe(II) catalyst
systems reported in literature. Sato and co-workers evaluated
iron-picolinate complexes as alcohol oxidation catalysts, oper-
ating at 5 mol% Fe. Under these conditions, their catalyst
oxidised 2-phenylethanol to 2-phenylethanone in 64% GC
yield (vs. 84% isolated yield for our catalyst system).47 Olivo
and co-workers applied an iron-base imine complex, with a
Entry Substrate
1
Major product
Isolated yieldb (%)
51 (81)
2
64 (68)
3*
4*
67 (70)
84 (100)
5*
6*
—
—
10 (96)
7*
8*
7 (87)
86 (>99)
a Reaction conditions: Complex R,R-C4 andS,S-C4 (0.5 mol%) in aceto-
nitrile with alcohol (0.8 mmol), AcOH (10 eq.) and H2O2 (4 eq.) at
298 K for 35 min. Conversions were determined by GC against an
internal standard (biphenyl). b Numbers in parentheses indicate the
average percentage substrate conversion from a duplicate set of runs.
For entries 3–8 the asterisk denotes that R,R-C4 was employed as cata-
lyst precursor.
excellent conversions and isolated yields were obtained for all catalyst concentration of 3 mol% and hydrogen peroxide as
the alcohols evaluated. Specifically, the addition of a methyl oxidant, to the oxidation of alcohols.48 Under their operating
group on the α-carbon had no effect on catalytic activity, conditions, 2-phenylethanol was oxidised to the ketone in 9%
evident when comparing 4-phenyl-2-butanol (Table 3, entry 1) GC yield. On the other hand, their catalyst system could
and 4-phenyl-1-butanol (Table 3, entry 2). In both instances oxidise cyclopentanol and cyclohexanol to the corresponding
comparable conversions and isolated yields were obtained. ketones in 54% and 70% GC yields respectively. Our Mn(II)
Employing 1-phenylethanol as substrate resulted in 100% con- complexes are outperformed by the current state of the art in
version and 84% isolated yield of acetophenone (Table 3, entry alcohol oxidation catalysis: a Cu(I)/ABNO (ABNO = 9-azabicyclo
4). The addition of a methyl group therefore, in this case, has [3.3.1]nonane N-oxyl,
a nitroxyl radical) catalyst system
an electron donating effect, increasing the oxidation reported by Stahl and co-workers.49 Operating at a copper con-
activity.11,20 In contrast, changing the methyl group on the centration of 5 mol%, 2-octanol and 4-phenyl-1-butanol could
α-carbon to a phenyl substituent resulted in no conversion, be oxidised to the ketone products in isolated yields of 96%
attributed to increased steric bulk hindering substrate and 95% respectively.
approach (Table 3, entry 5).17 In contrast, employing an ali-
phatic derivative such as 5-nonanol yielded the ketone product
in 67% isolated yield. This is significantly higher to that
Conclusions
reported in a previous study.43
Cyclic aliphatic alcohols, cyclohexanol and cyclopentanol, A series of R,R- and S,S-Mn(II) complexes, bearing BPMCN
were oxidised in good conversions of 96% and 87% respect- ligands and their derivatives (R,R-C1–C4 and S,S-C1–C4), were
ively (Table 3, entries 6 and 7). Unfortunately, very low isolated successfully applied as alcohol oxidation catalysts. In particu-
16540 | Dalton Trans., 2018, 47, 16534–16542
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Paper
lar, complexes bearing the novel BMIMCN ligand, R,R-C4 and 12 A. Murphy, A. Pace and T. D. P. Stack, Org. Lett., 2004,
S,S-C4, were found to be the most active. This highlighted the 6(18), 3119–3122.
stabilising effect that this ligand has on the catalytically active 13 O. Y. Lyakin, R. V. Ottenbacher, K. P. Bryliakov and
species. While high activity was observed for primary alcohol E. P. Talsi, ACS Catal., 2012, 2(6), 1196–1202.
oxidation, acid-mediated over-oxidation and side-reactions 14 R. V. Ottenbacher, D. G. Samsonenko, E. P. Talsi and
proved problematic. In contrast, secondary alcohols had no K. P. Bryliakov, Org. Lett., 2012, 14(17), 4310–4313.
such limitations and could be oxidised to the corresponding 15 M. Papastergiou, P. Stathi, E. R. Milaeva, Y. Deligiannakis
ketones in excellent isolated yields at short reaction times. and M. Louloudi, J. Catal., 2016, 341, 104–115.
Current work in our laboratory is directed toward elucidating 16 K. P. Bryliakov and E. P. Talsi, Coord. Chem. Rev., 2014, 276,
the mechanistic features of the oxidation reaction.
73–96.
17 D. Shen, C. Miao, D. Xu, C. Xia and W. Sun, Org. Lett.,
2015, 17(1), 54–57.
18 A. Berkessel and C. A. Sklorz, Tetrahedron Lett., 1999,
40(45), 7965–7968.
Conflicts of interest
There are no conflicts of interest to declare.
19 K. Nehru, S. J. Kim, I. Y. Kim, M. S. Seo, Y. Kim, S.-J. Kim,
J. Kim and W. Nam, Chem. Commun., 2007, (44), 4623–4625.
20 O. Cusso, I. Garcia-Bosch, D. Font, X. Ribas, J. Lloret-Fillol
and M. Costas, Org. Lett., 2013, 15(24), 6158–6161.
21 J. F. Larrow, E. N. Jacobsen, Y. Gao, Y. Hong, X. Nie and
C. M. Zepp, J. Org. Chem., 1994, 59(7), 1939–1942.
Acknowledgements
The work reported here is supported by the National Research
Foundation of South Africa, Unique Grant No. 99305 and 22 F. Galsbøl, P. Steenbøl and B. S. Sørensen, Acta Chem.
110694, North-West University Unique Grant No. P2A5B1 and Scand., 1972, 26(9), 3605–3611.
an Oppenheimer Memorial Trust Sabbatical Scholarship. Any 23 R. V. Ottenbacher, K. P. Bryliakov and E. P. Talsi, Inorg.
opinion, finding and conclusion or recommendation Chem., 2010, 49(18), 8620–8628.
expressed in this material is that of the author(s) and the NRF 24 SAINT, Version 8.38A, Bruker AXS Inc., 2017.
does not accept any liability in this regard. The infrastructure 25 G. Sheldrick, SADABS, Version 2012/1, Bruker AXS Inc.,
support provided by the Focus Area for Chemical Resource
2012.
Beneficiation (CRB) and in particular the Catalysis and 26 APEX3, Version 2017.3, Bruker AXS Inc., 2017.
Synthesis Research Group and Laboratory for Analytical 27 G. Sheldrick, Acta Crystallogr., Sect. C: Struct. Chem., 2015,
Services (LAS), at the NWU, is gratefully acknowledged. SASOL
71(1), 3–8.
postgraduate bursary support to VV is gratefully acknowledged. 28 L. J. Barbour, J. Supramol. Chem., 2001, 1(4), 189–191.
29 J. L. Atwood and L. J. Barbour, Cryst. Growth Des., 2003,
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30 R. Gopalan, Inorganic chemistry for undergraduates,
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