Synthesis of new metalloporphyrin derivatives from [5,10,15,20-tetrakis (pentafluorophenyl)porphyrin] and 4-mercaptobenzoic acid for homogeneous and heterogeneous catalysis

Article abstract of DOI:10.1016/j.apcata.2014.12.048

Synthetic metalloporphyrins are catalysts that can efficiently insert oxygen and other atoms such as nitrogen and sulfur in hydrocarbons and in a wide variety of other organic compounds. This work reports on a synthetic strategy to prepare new metalloporphyrins via structural modification of [5,10,15,20-tetrakis (pentafluorophenyl)porphyrin], or [H₂(TPFPP)], with 4-mercaptobenzoic acid; it also describes their characterization and catalytic activity. The substituent groups present in the structure of the resulting porphyrins furnished structured solids, which could potentially serve as catalysts in heterogeneous medium. Investigation of the catalytic activity of the new derivatives in the oxidation of (Z)-cyclooctene, cyclohexane, and heptane, under homogeneous conditions, and in the oxidation of (Z)-cyclooctene, in heterogeneous medium, proved that the new metalloporphyrins constituted excellent catalysts for (Z)-cyclooctene epoxidation. As for alkane oxidation, they selectively gave the corresponding alcohol in good yields.

Full text of DOI:10.1016/j.apcata.2014.12.048

Accepted Manuscript
Title: Synthesis of new metalloporphyrin derivatives from
[5,10,15,20-tetrakis (pentafluorophenyl)porphyrin] and
4-mercaptobenzoic acid for homogeneous and heterogeneous
catalysis
´
˜
Author: Kelly A.D.deF. Castro MarioM.Q. Simo es Maria da
´
Grac¸a P.M.S. Neves JoseA.S. Cavaleiro Ronny R. Ribeiro
Fernando Wypych Shirley Nakagaki
PII:
S0926-860X(14)00810-2
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.apcata.2014.12.048
APCATA 15187
To appear in:
Applied Catalysis A: General
Received date:
Revised date:
Accepted date:
7-11-2014
18-12-2014
25-12-2014
˜
Please cite this article as: K.A.D.F. Castro, M.M.Q. Simo es, M.G.P.M.S. Neves,
J.A.S. Cavaleiro, R.R. Ribeiro, F. Wypych, S. Nakagaki, Synthesis of new
metalloporphyrin derivatives from [5,10,15,20-tetrakis (pentafluorophenyl)porphyrin]
and 4-mercaptobenzoic acid for homogeneous and heterogeneous catalysis, Applied
Catalysis A, General (2015), http://dx.doi.org/10.1016/j.apcata.2014.12.048
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Highlights
Synthesis of new metalloporphyrin derivatives from [5,10,15,20-tetrakis
(pentafluorophenyl)porphyrin] and 4-mercaptobenzoic acid for homogeneous
and heterogeneous catalysis
1- Porphyrins preparation via [H2(TFPP)] structural modification with mercaptobenzoic
acid.
2- The substituent groups in the new porphyrins furnished structured solids.
3- New insoluble metalloporphyrins derivatives as catalysts in heterogeneous medium.
4- New metalloporphyrin derivatives as catalyst in the oxidation of alkenes and
alkanes.
5- New insoluble metalloporphyrin catalyst and its reuse capacity in oxidation reaction.
Page 1 of 49

Manuscript before reviewer’s suggestions
Synthesis of new metalloporphyrin derivatives from [5,10,15,20-tetrakis
(pentafluorophenyl)porphyrin] and 4-mercaptobenzoic acid for homogeneous
and heterogeneous catalysis
Kelly A. D. de F. Castro1,2, Mário M. Q. Simões2, Maria da Graça P. M. S. Neves2,*,
José A. S. Cavaleiro2, Ronny R. Ribeiro1, Fernando Wypych1, Shirley Nakagaki1,*
1Laboratório de Química Bioinorgânica e Catálise; Universidade Federal do Paraná
(UFPR), CP 19081, CEP 81531-990, Curitiba, Paraná, Brazil.
2Department of Chemistry and QOPNA, University of Aveiro, 3810-193 Aveiro,
Portugal.
* Corresponding authors: e-mail address: shirleyn@ufpr.br; gneves@ua.pt
Abstract
Inspired by the efficiency and selectivity of the reactions catalyzed by cytochrome P-
450, in recent years researchers have made great efforts to develop synthetic routes
that afford new porphyrins with different structures. Synthetic metalloporphyrins are
catalysts that can efficiently insert oxygen and other atoms such as nitrogen and sulfur
in hydrocarbons and in a wide variety of other organic compounds. Several studies
have shown that second-generation metalloporphyrins, which bear electronegative
and/or bulky substituents at the meso positions of the porphyrin ring, are more robust
and resist to prevent degradation during catalytic essays. This work reports on a
synthetic strategy to prepare new metalloporphyrins via structural modification of
[5,10,15,20-tetrakis (pentafluorophenyl) porphyrin], or [H2(TPFPP)], with 4-
Page 2 of 49

mercaptobenzoic acid; it also describes their characterization and catalytic activity.
The substituent groups present in the structure of the resulting porphyrins furnished
structured solids, which could potentially serve as catalysts in heterogeneous medium.
Investigation of the catalytic activity of the new derivatives in the oxidation of (Z)-
cyclooctene, cyclohexane, and heptane, under homogeneous conditions, and in the
oxidation of (Z)-cyclooctene, in heterogeneous medium, proved that the new
metalloporphyrins constituted excellent catalysts for (Z)-cyclooctene epoxidation. As
for alkane oxidation, they selectively gave the corresponding alcohol in good yields.
Keywords: porphyrin, 4-mercaptobenzoic acid, nucleophilic substitution,
homogeneous and heterogeneous catalysis, oxidation.
Page 3 of 49

1. Introduction
The use of synthetic macrocycles as catalysts in oxidation reactions has
generated great interest in bioinorganic chemistry [1,2], mainly when it comes to
modeling the proven catalytic ability of biological systems like cytochrome P-450 and
lignin peroxidases [3,4]. Researchers have successfully modulated the high
selectivity and chemical efficiency of catalytic systems based on these two heme
proteins they used synthetic metalloporphyrins bearing both simple and more
sophisticated structures [5-16]. They have developed these synthetic catalytic
systems [1,5,17,18] aiming to obtain complexes that can effectively generate
compounds in much the same way as cytochrome P-450 enzymes do. Examples of
such compounds are industrially important products like epoxides, alcohols, and
acids; compounds of pharmaceutical interest, namely specific isomers with
pharmacological activity, and high-purity precursors; and metabolites and drug
analogs. To obtain the desired catalytic selectivity for certain products, high degree of
sophistication may be necessary during the design of specific catalysts [1,17].
Work developed over the last 20 years has shown that catalysts based on
Fe(III) and Mn(III) complexes of synthetic meso-tetraarylporphyrins are the most
efficient and selective for oxidation reactions. The stereo-electronic features of the
substituents present in the aryl groups of these complexes exert an important effect
on the lifetime and reactivity of the active catalytic species in solution. These
substituents can inhibit the formation of dimeric species and prevent the auto-
oxidative destruction that inactivates the catalyst [5,12,19-23]. In fact, extensive
investigations have revealed that complexes of halogenated meso-
Page 4 of 49

tetraarylporphyrins are more robust and resistant to degradation by free radical attack
than those containing electron-donating substituents. These systems constitute
effective catalysts for the oxidative insertion of oxygen in organic compounds, namely
hydrocarbons; they can also transfer an oxygen atom to sulfur- and nitrogen-
containing substrates with great efficacy [3,24-30]. Additionally, the pharmaceutical
industry has explored these systems to prepare oxidized metabolites from drugs [3].
In particular, the complexes of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin,
[H2(TPFPP)], an excellent template for further functionalization with nucleophiles [31-
33], have found promising applications in catalysis [8,9,11,13,15,19,34] and in other
areas [36-40]. It is easy to prepare catalytically active polymeric metalloporphyrins by
reacting [H2(TPFPP)] or the corresponding metal complexes with polyethylene glycol
in the presence of sodium hydride using toluene as solvent [41]. The same template
[H2(TPFPP)] has been used to obtain derivatives with adequate amphiphilicity for
application as photosensitizers that can photodynamically inactivate microorganisms
[42,43].
Recently, we have reported that metalloporphyrins with appended ethylene
glycol substituents efficiently catalyze (Z)-cyclooctene and cyclohexane oxidation
under homogeneous and heterogeneous conditions [34].
Considering our research interest in the synthesis of efficient catalysts based
on [H2(TPFPP)] functionalization, here we report on the synthesis and catalytic
activity of new metalloporphyrins obtained by structural modification of [H2(TPFPP)]
with 4-mercaptobenzoic acid. Depending on the number of para-fluorophenyl
substituents that 4-mercaptobenzoic acid replaces during the synthesis, further metal
insertion into the porphyrin complex will afford structured solids that are insoluble in
Page 5 of 49

most of the tested solvents. We investigated the catalytic activity of the synthesized
metallocomplexes in (Z)-cyclooctene, cyclohexane, and heptane oxidation under
homogeneous and heterogeneous catalytic conditions. We also assessed
solid/heterogeneous catalysts recovery and reuse in the case that (Z)-cyclooctene
was the substrate.
2. Experimental section
All the chemicals used in this study were purchased from Aldrich, Sigma, or
Merck and were of analytical grade. Iodosylbenzene (PhIO) was synthesized by
hydrolysis of iodosylbenzenediacetate [44], and the obtained solid was carefully dried
under reduced pressure and kept at 5 °C.
2.1. Synthesis of metalloporphyrins (see Figure 1 for abbreviations)
The synthesis of the new metalloporphyrins involved three steps:
(i) Synthesis of Porphyrin P1: the porphyrin ligand was prepared as described in the
literature [45,46].
(ii) Synthesis of the free-base porphyrins P2, P3, P4, P5, and P6 from reaction of 4-
mercaptobenzoic acid with porphyrin P1 (Figure 1): In a round-bottom flask, 0.4 mmol
of 4-mercaptobenzoic acid was dissolved in 15 mL of DMF containing 0.5 mL of
pyridine. The reaction mixture was kept under magnetic stirring at room temperature
for 30 min. Porphyrin P1 (0.1 mmol) was added, and the reaction mixture was kept
under magnetic stirring for 3 h and monitored by TLC. Then, the solvent was
evaporated under reduced pressure, and the crude solid was purified by preparative
Page 6 of 49

TLC (thin-layer chromatography - silica was the stationary phase, and
chloroform/methanol (9:1 v/v) was the mobile phase). In this process, several
fractions were separated and numbered from 1 to 5.
The first fraction was identified as porphyrin P2 (19% yield), m.p. > 300 °C. 1H
NMR: H ppm (CD3OD) 9.20 (broad, 8H, H-), 8.07 (d, J = 9 Hz, 2H, S-C6H4-CO2H),
19
and 7.66 (d, J = 9 Hz, 2H, S-C6H4-CO2H). F NMR: F ppm (CD3OD) -188.35 to -
188.17 (m, 6F, F-meta), -178.57 (t, J = 20.0 Hz, 3F, F-para), -163.67 (dd, J = 7.5 and
22.8 Hz, 6F, F-ortho), -162.80 (dd, J = 12.3 and 24.3 Hz, 2F, F-meta), and -158.51
(dd, J = 12.3 and 24.3 Hz, 2F, F-ortho). UV–VIS (CHCl3) λmax, nm (log ): 414 (5.20),
506 (4.08), 584 (3.90). HRMS (FAB+) m/z: calcd for C51H16F19N4O2S (M+H)+:
1109.0685; found: 1109.0667. The second and third fractions were identified as
1
porphyrins P3 and P4. Porphyrin P3 (17% yield), m.p. > 300 °C. H NMR: H ppm
(CD3OD): 9.18 (broad, 8H, H-), 8.08 (d, J = 8.4 Hz, 4H, S-C6H4-CO2H), and 7.67 (d,
J = 8.4 Hz, 4H, S-C6H4-CO2H). 19F NMR: F ppm (CD3OD) -188.67 to -188.49 (m, 4F,
F-meta), -179.01 (t, J = 20.4 Hz, 2F, F-para), -163.73 (dd, J = 7.8 and 23.0 Hz, 4F, F-
ortho), -162.89 (dd, J = 12.2 and 24.4 Hz, 4F, F-meta), and -158.68 (dd, J = 12.2 and
24.4 Hz, 4F, F-ortho). UV–vis (CHCl3) λmax, nm (log ): 412 (5.24), 506 (4.06), 584
(3.90). HRMS (FAB+) m/z: calcd for C58H21F18N4O4S2 (M+H)+: 1243.0711; found:
1243.0696. Porphyrin P4 (12% yield), m.p. > 300 °C. 1H NMR: H ppm (CD3OD): 9.18
(broad, 8H, H-), 8.08 (d, J = 8.2 Hz, 4H, S-C6H4-CO2H), and 7.67 (d, J = 8.2 Hz, 4H,
S-C6H4-CO2H). 19F NMR: F ppm (CD3OD) -190.20 to -190.03 (m, 4F, F-meta), -
180.54 (t, J = 20.2 Hz, 2F, F-para), -165.27 (dd, J = 7.3 and 22.6 Hz, 4F, F-ortho), -
164.41 (dd, J = 12.3 and 24.5 Hz, 4F, F-meta), and -158.68 (dd, J = 12.3 and 24.5
Page 7 of 49

Hz, 4F, F-ortho). UV–vis (CHCl3) λmax, nm (log ): 412 (5.22), 506 (4.08), 582 (3.66).
HRMS (FAB+) m/z: calcd for C58H21F18N4O4S2 (M+H)+: 1243.0711; found: 1243.0675.
1
The fourth fraction was identified as porphyrin P5 (37% yield), m.p. > 300 °C. H
NMR: H ppm (CD3OD): 9.24 (broad, 8H, H-), 8.16 (d, J = 8.4 Hz, 6H, S-C6H4-
CO2H), and 7.75 (d, J = 8.4 Hz, 6H, S-C6H4-CO2H). 19F NMR: F ppm (CD3OD) -
190.19 to -190.02 (m, 2F, F-meta), -180.53 (t, J = 20.4Hz, 1F, F-para), -165.25 (dd, J
= 7.6 and 22.6 Hz, 2F, F-ortho), -164.40 to 164.21 (m, 4F, F-meta), and -160.20 (dd,
J = 12.3 e 24.7 Hz, 4F, F-ortho). UV–VIS (CH3OH) λmax, nm (log ): 410 (5.16), 504
(4.13), 582 (3.65). HRMS (FAB+) m/z: calcd for C65H26F17N4O6S3 (M+H)+: 1377.0738;
found: 1377.0737. The protons signal relative to N-H was not observed, due to their
replacement by deuterium from deuterated methanol in porphyrins P2-P6. Finally, the
1
fifth fraction was identified as porphyrin P6 (3.1% yield), m.p. > 300 °C, H NMR: H
ppm (Acetone-d6) 9.46 (broad, 8H, H-), 8.14 (d, J = 8.4 Hz, 8H, S-C6H4-CO2H),
7.82 (d, J = 8.3 Hz, 8H, S-C6H4-CO2H), and -2.87 (s, 2H, NH). 19F NMR: F ppm
(Acetone-d6) -162.02 (dd, J = 11.9 and 24.7 Hz, 8F, F-meta), and -157.70 (dd, J =
11.9 and 24.7 Hz, 8F, F-ortho). UV–VIS (Acetone) λmax, nm (log ): 412 (5.14), 504
(4.07), 582 (3.57). HRMS (FAB+) m/z: calcd for C72H31F16N4O8S4 (M+H)+: 1511.0764;
found: 1511.0752.
The reaction yields described above were obtained after 3 h of reaction; when
the reaction conducted under the same conditions was stopped after 1 h, the yield of
porphyrin P2 was higher 33.6%; porphyrins P3 and P4 were isolated in yields ranging
from ca. 15 to 25%. To optimize the formation of porphyrin P6, the reaction was
performed as described previously, but 0.72 mmol of 4-mercaptobenzoic acid, 15 mL
Page 8 of 49

of DMF, 4.0 mL of pyridine, and 0.102 mmol of porphyrin P1 were used instead. After
48 h of reaction, porphyrin P6 was isolated in 96% yield.
(iii) Preparation of manganese, iron, and copper porphyrins (MPx): To insert a metal
into the free-base porphyrins P1, P2, and P6, a modification of the conventional
method described by Kobayashi47 was employed. To obtain the iron complexes, the
reactions were carried out using acetic acid (P1) or DMF (P2 and P6) as solvent,
iron(II) chloride, and sodium acetate (to aid deprotonation). The reactions were
performed under reflux in argon atmosphere for 24 h, to yield FeP1, FeP2, and FeP6
(confirmed by the observation of the characteristic bands by UV-VIS analyses), The
argon atmosphere was removed and solution reaction was kept under magnetic
stirring at reflux system to ensure the total oxidation of Fe (II) to Fe (III).
To achieve the manganese complexes, manganese(II) acetate was used in the
same solvents used for iron(III) metallation process. The reaction was conducted for 8
h, to afford MnP1, MnP2, and MnP6. The oxidation of Mn(II) to Mn(III) was also
performed in air as described for FeP.
Copper was also inserted into porphyrins P1 and P6, using copper(II) acetate,
DMF as solvent, and reaction time of 3 h, to give CuP1 and CuP6. After metal
insertion, the solvents were removed under vacuum. The resulting solids were
thoroughly washed with water, to remove excess metal salts. The complexes were
purified by column chromatography using dichloromethane as eluent. The
preparation of CuP2 was not performed in this stage, since the material amount (free
base porphyrin) was insufficient.
Page 9 of 49

During metal insertion into porphyrin P6, the corresponding metalloporphyrins
(MnP6, FeP6, and CuP6) precipitated, and the resulting crude solids were insoluble
in all the tested solvents. The other synthesized metalloporphyrins (CuP1, FeP1,
FeP2, MnP1, and MnP2) behaved differently and the crude solids were soluble in
different solvents and were purified by column chromatography.
2.2. Catalytic oxidation reactions
The following procedure was adopted to assess the oxidation of different
substrates catalyzed by the previously prepared metalloporphyrins: about 1.0 mg of
the metalloporphyrin was weighed in a 2-mL thermostatic glass reactor tube
equipped with a magnetic stirrer. The reactor tube was placed inside a dark recipient,
and iodosylbenzene was added, to obtain a 1:10 catalyst/oxidant molar ratio. The
reactor was degassed with argon for 15 min, which was followed by addition of the
solvent (acetonitrile, 400 L) and the substrate ((Z)-cyclooctene, cyclohexane, or
heptane). The oxidation reactions were carried out under magnetic stirring for 1 h or
24 h. (Z)-Cyclooctene had been previously purified by column chromatography on an
alumina micro column. The reactions were quenched by addition of sodium sulfite
saturated solution (approximately 0.1 mol/L), to eliminate excess PhIO. The reaction
mixture was transferred to a volumetric flask, and aliquots were analyzed by gas
chromatography after addition of the internal standard (a solution of 99.9% octan-1-ol
in acetonitrile 1.0 x 10-2 mol/L). When the catalyst used in the reaction was insoluble
(FeP6, MnP6, and CuP6), the solid catalyst was washed several times with methanol
and acetonitrile after the reaction, to extract any reaction products that might have
Page 10 of 49

adsorbed onto the solid. The washing solutions were added to the previously
separated reaction supernatant, and the contents of these combined solutions were
analyzed by gas chromatography, also using octan-1-ol as internal standard. The
product yields were based on the amount of PhIO added to the reactions. The molar
ratio 1:10 catalyst/oxidant was estimated based on molecular mass of MP including
the insoluble solids catalysts. Control experiments were also carried out in the
absence of MPx using the methodology described above.
The insoluble solids FeP6, MnP6, and CuP6 were recovered after the first use
and washed with water, methanol, acetonitrile, and dichloromethane, dried at 55 °C
for 48 h, and reused in further reactions. The resulting washing solutions of all the
recovered catalysts were analyzed by UV-VIS spectroscopy, to investigate the
presence of metalloporphyrin in any of the washing solutions of these solid catalysts.
Characterization Techniques
Electronic spectra (UV-VIS) were obtained on a Cary-Varian and Shimadzu UV-
2501PC spectrophotometer, in the 350-700 nm range. Spectra of the solid samples
were recorded in a 0.1 cm path length quartz cell (Hellma) in nujol mull. Transmission
Fourier Transform Infrared (FTIR) spectra were registered on an FT Mattson 7000
galaxy spectrophotometer in the 400-4000 cm-1 range, using KBr pellets. KBr was
ground with a small amount of the solid to be analyzed, and the spectra were collected
1
19
with a resolution of 4 cm-1 and accumulation of 64 scans. H and F NMR spectra
were recorded on a Bruker Avance 300 spectrometer at 300.13 and 282.38 MHz,
respectively. Deuterated methanol, acetone, and chloroform were used as solvents;
TMS ( 0 ppm) was the internal standard. The chemical shifts are reported in ppm (),
Page 11 of 49

and the coupling constants (J) are given in Hz. Mass spectra were acquired on a 4800
Proteomics Analyzer mass spectrometer (MALDI TOF/TOF), and HRMS were
recorded on VG AutoSpec Q and M mass spectrometers. Electron paramagnetic
resonance (EPR) measurements of the powder materials were accomplished on an
EPR BRUKER EMX microX spectrometer (frequency X, band 9.5 GHz), at room
temperature and 77 K (using liquid N2), using perpendicular microwave polarization X-
band. Analyses at 77 K parallel microwave polarization X-band EPR experiments were
conducted on a Bruker Elexsys E500 spectrometer equipped with a Bruker
ER4116DM dual mode resonator. Products from the catalytic oxidation reactions were
quantified using a gas chromatograph Agilent 6850 (FID detector) equipped with a DB-
WAX capillary column (J&W Scientific). Quantitative analysis was accomplished by the
internal standard method.
3. Results and discussion
3.1. Synthesis of porphyrin derivatives P2-P6 from the reaction of P1 with 4-
mercaptobenzoic acid
The synthesis of the free-base porphyrins P2-P6 (Figure 1) relied on the well-
established reactivity of the p-fluorine atoms in the presence of nucleophiles [48,49].
Sulfur-containing derivatives like thiols constitute excellent nucleophiles for this type
of functionalization. Indeed, the first synthesis reported in the 1990s involved the
reaction between the zinc(II) complex of [H2(TPFPP)] with butane-1-thiol, to give the
corresponding tetra-substituted metalloporphyrin in 85% yield [28,51].
Here, it was reacted porphyrin P1 with 4-mercaptobenzoic acid (MERC)
previously treated with pyridine in DMF, at room temperature. The yields of mono-
Page 12 of 49

(P2), di- (P3 and P4), tri- (P5), and tetra- (P6) substituted porphyrins (Figure 1)
depended on the reaction time and on the amount of 4-mercaptobenzoic acid.
After 1 h of reaction, a MERC/P1 molar ratio of 4:1 preferentially afforded the
mono-substituted porphyrin P2 (34% yield), along with porphyrins P3 and P4 in yields
ranging from 15 to 25% and unreacted porphyrin P1 (20%). Under the same
conditions but using a reaction time of 3 h, it was possible to isolate all the porphyrins
as a complex mixture of P2, P3, P4, P5, and P6 in 19%, 17%, 12%, 37%, and 3%
yield, respectively. It was successfully optimized the formation of the tetra-substituted
porphyrin P6 to 96% yield by performing the reaction in the presence of large excess
of 4-mercaptobenzoic acid (0.7 mmol) relative to the amount of porphyrin P1 (0.1
mmol), using 4.0 mL of pyridine and extending the reaction time to 48 h.
After purification by preparative TLC, all the new compounds was
1
characterized by UV–VIS and FTIR spectroscopies, H and 19F NMR, and high-
resolution mass spectrometry (HRMS, FAB+) (see experimental part and Supporting
information-Figures S1- S12). As expected, the less polar fraction (higher Rf)
corresponded to the mono-substituted derivative P2, which bore a single MERC
group. The two fractions that came just behind and had very close Rf referred to the
di-substituted derivatives P3 and P4, followed by the tri-substituted P5, and finally by
the most polar fraction, the tetra-substituted P6. The attribution of P3 (trans) and P4
(cis) was made in accordance with the expected polarity [34].
Page 13 of 49

F
F
F
F
F
F
F
F
F
F
F
F
F
NH N
N HN
F
F
F
F
F
F
F
P1
P2- R1 = SC6H4COOH; R2= R3 = R4 = F
P3- R1 = R3 = SC6H4COOH; R2 = R4 = F
+
HO
O
*
SH
P4-
=
SC H COOH
= F
; R2 = R3
R1 R4
=
6 4
P5- R1 = R3 = R4 = SC6H4COOH; R2 = F
P6- R1 = R2 = R3 = R4 = SC6H4COOH
3 h
1 h
48 h
R4
R4
F
F
F
F
F
F
F
F
F
F
F
F
F
F
F
F
F
F
F
F
F
F
F
NH N
N HN
NH N
N HN
R4
R1
R3
R1
R3
F
F
F
F
F
F
F
F
F
F
F
F
F
F
F
F
F
F
F
F
NH N
N HN
R1
R3
R2
R2
F
P2 P3
P4
,
and
P2 P3 P4 P5 P6
and
,
,
,
F
F
F
F
R2
P6
* pretreated with pyridine for 30 min. at room temperature
Figure 1. Schematic representation of the reactions between porphyrin P1 and 4-
mercaptobenzoic acid (MERC), to obtain the derivatives P2 - P6.
1
The H NMR spectra of the new porphyrins showed the appearance of two
characteristic signals in the aromatic region: in the region of δ 7.65-7.68 ppm shaped
doublet (J = 8.4 Hz, 2H) and one doublet in the region of δ 8.05 to 8.08 ppm (J = 8.4
Page 14 of 49

Hz, 2H), corresponding to resonance of protons S-R and R-CH=CH-CO2H,
respectively. This is a direct evidence of MERC presence in the derived products.
The new porphyrins P2-P6 exhibited the typical FTIR bands of free-base
porphyrins, in addition to the bands characteristic of MERC binding to porphyrin P1 at
3438 cm-1 (OH stretching) and at 1694 and 1486 cm-1 (C=O stretching) (Supporting
information-Figure S11).
The UV–VIS spectra of porphyrins P2-P6 presented slightly broader bands as
compared with the bands observed for porphyrin P1, attributed to the presence of the
new substituents (Supporting information-Figure S12). The highly successful “four-
orbital” model explains the origin and the number of bands observed in the spectra of
the free-base porphyrins [52]: changes in the porphyrin ring can affect the UV–VIS
absorption spectrum, so the broadened Soret band of the new compounds (P2-P6)
may stem from greater interaction of the substituted phenyl groups with the porphyrin
ring and/or from some intermolecular aggregation.
3.2. Preparation of manganese, iron, and copper porphyrins (MPx)
To obtain the Fe(III) and Mn(III) complexes of porphyrins P2 and P6 and the
Cu(II) complex of P6 for further use in the catalytic studies, we treated the free bases
with the appropriate iron(II), manganese(II), or copper(II) salts under conventional
conditions. As expected, the free-base porphyrin P2 afforded the corresponding
complexes FeP2 and MnP2 (Figure 2), which were soluble in most organic solvents
(FeP2 (C51H13F19FeN4O2S): UV–VIS (CH3OH) max, nm: 412, 506 and 584;
MALDI (TOF/TOF) (m/z):1161.9 [M+H]+ and HRMS (FAB+) (m/z): 1161.9800
Page 15 of 49

corresponding
to
the
calculated
formula
C51H13F19FeN4O2S.
MnP2
(C51H13F19MnN4O2S): UV–VIS (CH3OH) max, nm: 460 and 556; ESI-MS m/z: calcd
for C51H13F19MnN4O2S (M-2H): 1158.99; found: 1158.99 - Supporting information -
Figures S13, S14 and S15). The displacement of Soret band and the reduction of
number of Q-bands resulted from alteration in the microsymmetry of the porphyrin
macrocycle from D4h to D2h, a consequence of the presence of the Fe(III) or Mn(III)
ion in the porphyrin core. This symmetry chance can be explained by the orbitals
analysis as described by Goutermann [52].
A different situation emerged in the case of porphyrin P6. For the three metal
ions used in this work, metal insertion into porphyrin P6 culminated in precipitation of
the resulting metalloporphyrin at the end of the reaction, which constituted an
unexpected outcome indeed, metalloporphyrins do not generally precipitate in the
solvent where the free-base is soluble [47]. However, the solids originating from
metal insertion into porphyrin P6 (FeP6, MnP6, and CuP6) exhibited a different
solubility pattern from that of free-base P6: they were all only slightly soluble in
solvents where the free-base P6 was very soluble (e.g., DMF, THF, and acetone) as
well as in other tested solvents (CHCl3, CH2Cl2, CH3OH, toluene, ethanol,
acetonitrile, and H2O). Compared with P6 and MP2, the low solubility of MP6
suggested formation of a structured solid as in the case of solids known as metal
organic frameworks (MOFs) [53].
Page 16 of 49

R4
F
F
F
F
3+
FeP1 -
MnP1-
F
R1 = R2= R3 = R4 = ; M = Fe
F
F
F
F
F
F
F
F
3+
= = F
R1 R2= R3 = R4 ; M = Mn
L
N
N
N
N
CuP1- R1 = R2= R3 = R4 = F; M = Cu2+
R3
R1
M
3+
FeP2 -
SC H COOH
=
= F
; M = Fe
R1 =
; R2 = R3 R4
6
4
3+
FeP6 -
=
=
SC H COOH
; M = Fe
R1 R2 = R3 R4 =
6
4
MnP2 - R1 = SC6H4COOH; R2 = R3 = R4 = F; M = Mn3+
F
F
F
F
3+
MnP6 -
CuP6 -
=
SC H COOH
; M = Mn
R1 = R2 = R3 R4 =
6
4
2+
=
=
SC H COOH
R1 R2 = R3 R4 = ; M = Cu
6 4
R2
Figure 2. Schematic representation of iron(III), manganese(III), and copper(II) porphyrins,
where L represents the counter-ion (chloride or acetate) for FeP and MnP, respectively. For
simplification purposes the counter-ion was omitted on the name of all compounds used in
this work.
MOFs are solids that originate from binding between organic or inorganic
molecules and metal clusters, which results in a robust and often nanoporous bi- or
tridimensional supramolecular structure [12,54]. Supramolecular systems based on
porphyrins can display various kinds of interactions: a ligand group can interconnect
the macrocycles (van der Waals interactions), or one donor atom present in the
metalloporphyrin can bind to the metal center of another metalloporphyrin [12].
The assumption that a structured solid arose during metal insertion into
porphyrin P6 relied on the fact that the porphyrin structure contained carboxylic acid
groups. Suslick et al. [55] reported that porphyrins displaying peripheral carboxylic
groups favor the formation structured solid via coordination of the carboxyl groups
with the metal ions, to give rise to bi-and tridimensional structures of the solid. In a
Page 17 of 49

similar way, porphyrins containing terephthalic acid as substituents in the porphyrin
ring tended to form structured solid [56].
UV–VIS, FTIR, and EPR spectroscopies as well as mass spectra (Figures
S14, S15, S16 and S17-Supporting information) helped to characterize the prepared
metalloporphyrins. Compared with data obtained for the free-base porphyrins, the
UV–VIS spectra of the metalloporphyrins confirmed insertion of the three different
metal ions into porphyrin P6 (Supporting information-Figures S12 and S13). Figure 3
depicts the UV–VIS spectra of solid MP6 and includes the spectrum of porphyrin P6
for comparison (in Nujol mull). The spectrum of free-base P6 (Figure 3a) displayed
Soret band in the region of 400 nm as well as the typical Q bands in the visible
region, as expected for this free-base porphyrin [31]. The insoluble MP6 presented a
reduced number of bands in the visible region (from three to one, as expected), in
addition to the typical Soret band of each complex. For FeP6 and CuP6, the Soret
band did not shift significantly. As expected, Mn(III) ion insertion into the free-base
porphyrin elicited a large bathochromic shift of the Soret band [52,57,58]. In other
words, the UV–VIS spectra of the solids MP6 presented the typical bands of
metalloporphyrins, attesting that the insoluble solids (FeP6, MnP6, and CuP6) really
referred to metallated P6. The synthesized MP6 probably consisted of structured
solids containing metalloporphyrins as building blocks. However, despite the
evidence obtained from the UV–VIS spectra and the solubility behavior, it is difficult
to safely infer any structural or chemical information about the solids obtained from
metal insertion into porphyrin P6.
Page 18 of 49

(d)
(c)
(b)
(a)
400
500
600
700
800
Wavelength (nm)
Figure 3. UV–VIS spectra of the solid samples dispersed in Nujol mull: (a) Free-base
porphyrin P6, (b) FeP6, (c) MnP6, and (d) CuP6.
The EPR spectra showed that the iron porphyrins (FeP2 and FeP6, Figure 4)
displayed signals characteristic of high-spin Fe(III), S = 5/2, in the region of axial
symmetry g// = 6.0, as well as a signal with low intensity in the region of g = 4.3, typical
of rhombic symmetry [59-61].
g = 4.23
(a)
g = 5.83
g = 4.23
(b)
g = 5.84
1000
1200
1400
1600
1800
2000
Magnetic Field (Gauss)
Figure 4. EPR spectra in solid sample at room temperature: (a) FeP2 and (b) FeP6.
Page 19 of 49

The perpendicular microwave polarization X-band EPR analysis of the MnP2
compound was EPR silent (Figure not shown) but the solid MnP6 revealed a broad
isotropic signal in the region of g = 2.0, which can correspond to the presence of Mn(II)
species. In this case, the Mn(II) ion, a system with five electrons in an environment of
D4h symmetry, is expected to exist. This system is paramagnetic and EPR active [62]
(Supporting information- Figure S17).
Considering that the metal in MnP2 (Soret band at 460 nm) and MnP6 must be
Mn(III), as inferred from the UV–VIS spectrum (Figure 3c), these metalloporphyrin
should not have presented any EPR signals; that is, it should be EPR silent on
perpendicular microwave polarization X-band EPR [63]. This absence of signal was
observed for the MnP2 EPR analysis but nevertheless, as described in the previous
paragraph, an EPR signal emerged at g = 2.0 (Figure S17) for the solid MnP6, which
could refer to the existence of Mn(II) ions that probably acted as coordinative ions for
the peripheral acid groups present in the ring of porphyrin P6. This coordination should
generate and stabilize the structured solid MnP6 [12].
To confirm the presence of Mn(III) in MnP2 and MnP6 by EPR, it was used the
non-conventional polarization of the microwave field, parallel to the external magnetic
field. This technique shows signals corresponding to forbidden transitions; i. e.,
transitions with |ΔmS| > 1 [63,64]. The Zero Field interaction (ZF) present in the Mn(III)
(S = 2) magnetic system causes the spin-related energy level to split into three levels.
These levels correspond to the effective spin angular momenta of S = 2, S = 1, and S
= 0, separated by -6D, 3D, and 6D related to the energy barycenter, respectively, for
Page 20 of 49

positive values of the Zero Field Splitting parameter, D, which is a measure of the
intensity of the ZF interaction.
Application of the parallel microwave polarization technique to MnP2 and the
solid MnP6 evidenced the transition mS = -2 → mS = +2 in the lowest-energy spin
level, S = 2. The transition corresponded to |ΔmS| = 4 and occurred around g ~ 8.9
(750 G), as expected (Figure 5).
(a)
(b)
|mS| = 4, Mn(III)
|mS| = 4, Mn(III)
250
500
750
1000
1250
1500
1750
2000
250
500
750
1000
1250
1500
1750
2000
Magnetic Field (Gauss)
Magnetic Field (Gauss)
Figure 5. EPR spectra in the polarization parallel to the magnetization axis of the solid MnP
samples at 77 K: (a) MnP2 and (b) MnP6.
Both MnP2 and MnP6 exhibited a signal at g ≃ 8.9, ascribed to a transition
with |ΔmS| = 4, related to the presence of Mn(III) species (Figure 5). This suggested
that both complexes contained Mn(III), which probably inserted in the inner core of
porphyrins P2 and P6. The presence of this signal and also the intense signal
Page 21 of 49

associated with Mn(II) present in the perpendicular spectrum of solid MnP6 (Figure
S17) suggested that the Mn(II) ion might play a structuring function in the
metalloporphyrin Mn(III)P6, to give structured solid MnP6, which is responsible by the
high insolubility of this solid in comparison to MnP2.
The Cu2+ ion presents a d9 electronic configuration with one unpaired electron.
This makes the EPR technique a valuable tool to investigate copper complexes [65].
The EPR spectrum of Cu(II) provides valuable information regarding the oxidation
state, binder type, and symmetry of copper compounds. Cu(II) is an S=1/2 system,
but 63Cu and 65Cu nuclei have a nuclear spin of I=3/2, which gives rise to the
hyperfine splitting between the unpaired electron and the nucleus itself. Thus, the
EPR spectrum of a Cu(II) complex consists of four lines with large g in the region of
2.0 [65,66]. The EPR spectrum of solid CuP6 (Figure 6a) presented the characteristic
anisotropic signal for Cu(II), S = 3/2, in axial symmetry in the region around g = 2.0.
To investigate the solubilization behavior of the insoluble solid CuP6, we
dissolved a sample of this solid in a solution of acetic acid (2 mol/L) and evaporated it
to dryness, to obtain another solid, designated CuP6-d. The EPR spectrum of CuP6-
d (Figure 6b) displayed the typical EPR pattern of Cu(II), accompanied by a multiple
line pattern in the perpendicular region of the spectrum. The latter pattern is
characteristic of super-hyperfine interaction of the copper ion unpaired electron with
four magnetically equivalent 14N nucleus (I=1). The appearance of these signals in
the EPR spectrum of the solid CuP6-d suggested that the previously structured solid
CuP6 probably broke in the presence of acid. This might have occurred via a
protonation process or de-coordination of metal ions, to give CuP6 in solution as well
as free copper ion and copper ion coordinated to acetate ions.
Page 22 of 49

Interestingly, CuP6-d was very soluble in acetone, in contrast to solid CuP6
(analyzed by EPR as illustrated in Figure 6a), which only became soluble in acetone
after being solubilized in acetic acid.
(a)
(b)
2500
3000
3500
4000
Magnetic Field (Gauss)
Figure 6. EPR spectra of solid samples at 77 K: (a) solid CuP6 and (b) solid resulting from
CuP6 dissolution with acetic acid solution (2 mol/L), after evaporation of the acid solution
(designated solid CuP6-d).
The EPR spectrum of CuP6-d dissolved in acetone, recorded in frozen solution
(at 77 K) conditions (Figure 7a), provided better resolution of the typical Cu(II) lines of
the hyperfine and super hyperfine interaction of this ion with the four nitrogen
coordinative ligands of the porphyrin macrocycle. Table 1 compiles the EPR
parameters obtained by simulating the experimental spectrum (Figure 7b) using the
Page 23 of 49

Easyspin software package [67]. These values agreed with those obtained for
metalloporphyrins with D4h symmetry (square planar) around the Cu(II) ion, as
expected.
Figure 7. (a) EPR spectrum of the frozen solution (at 77 K) of the solid CuP6-d in acetone.
(b) Simulation of the EPR spectrum.
Table 1: Spin Hamiltonian parameters for the X-band EPR spectral simulationsa conducted
for CuP6 dissolved in acetic acid solution (2 mol/L), dried, and redissolved in acetone (frozen
solution EPR spectrum at 77 K) (Figure 7b).
Main direction
g tensor
A tensor [MHz]
63, 65Cu
14N
Page 24 of 49

Perpendicular
Parallel
2.05044
2.20124
58.0625
599.479
45.3597
52.0477
aThe EPR parameters listed in the table were obtained by simulating the experimental spectrum at
77K in acetone solution using the Easyspin pack software.
The diffractogram of the starting salt Cu(OAc)2 resembled the diffraction pattern
reported in the literature [68]. The PXRD pattern of CuP6 (Figure 8b) was different
from the diffraction pattern of the starting material. An intense peak arose at 2 =
13.26◦, corresponding to a distance of 6.7 Å (001). Another peak appeared at 2 =
26.64◦, relative to a short distance (around 3.35 Å) (002). Moreover, diffraction peaks
emerged between 5-10º (2), as observed for other MOFs [69,70].
Resolvation and drying under vacuum helped to investigate the robustness of
the material [69]. First, re-exposure of the CuP6 powder to DMF induced resolvation.
Then, exhaustive drying of CuP6 under vacuum at room temperature eliminated
traces of the solvent DMF. Next, analysis of the resulting solid by PXRD (Figure 8c)
did not evidence any significant modifications. In fact, CuP6 retained its crystallinity,
which was consistent with the crystallinity of fresh CuP6 and was characteristic of
materials with good gas-occlusion properties [70].
Overall, the solid compounds resulting from iron, copper, and manganese
insertion into porphyrin P6 were highly insoluble. Elemental analysis of solids FeP6,
MnP6, and CuP6 were not consistent with the structure expected for molecular MP6
complexes. The solubility of the resulting solid complexes in acidic medium suggested
a break in their structure, as evidenced by detection of free tetra-substituted MP6 in
solution (structure confirmed by mass spectra (ESI-MS) as opposed to a
Page 25 of 49

supramolecular structure containing MP6 building blocks connected by metal ions
coordinated to the donor atoms of the meso-aryl substituents (Figure S17-Supporting
information). Additionally, the EPR spectrum for compound MnP6 corroborated the
presence of manganese in different oxidation state. This indicated that Mn(III)
porphyrins constituted building blocks of the solid, and that Mn(II) species probably
acted as construction units.
(c)
(b)
(a)
5
10
15
20
25
30
35
40
2  (Degree)
Figure 8. PXRD patterns of the solid CuP6 indicate that crystallinity is maintained in the
absence of guest molecules. (a) Cu(AcO)2, (b) CuP6, and (c) CuP6 after drying for 2 h and
redissolution.
3.3. Catalytic oxidation reactions
The catalytic efficiency of MPx was evaluated under homogeneous (FeP2 and
MnP2) and heterogeneous (FeP6, MnP6, and CuP6) conditions, in the oxidation of
(Z)-cyclooctene, cyclohexane, and heptane. To assess whether the presence of
Page 26 of 49

MERC groups affected the well-known catalytic ability of metallocomplexes of the
starting porphyrin P1, we also report results obtained with FeP1, MnP1, and CuP1
[5,71-73].
To simplify the discussion and for comparison purposes, the results concerning
each substrate was showed separately,. All the catalytic studies were conducted
under similar reaction conditions for both the homogeneous and the heterogeneous
catalytic systems.
(Z)-Cyclooctene
(Z)-Cyclooctene is a substrate that is easy to oxidize in reactions catalyzed by
metalloporphyrins [74]. The corresponding epoxide emerges as a single product. This
behavior is usually justified by the higher stability of the intermediate involved in the
formation of the epoxide as compared with the intermediate leading to the eight-
membered allyl radical ring [2,75,76]. The proton abstraction from the allyllic position
of cis-cyclooctene generates a less stable radical than proton abstraction from the
vinyllic position. The allylic radical acquires an unfavorable configuration due trans
interactions that can occur between the hydrogen atoms. To maintain the
unsaturation and the radical structure in the same plane, the chain of allylic radical
becomes distorted and, thus, less stable.
Table 2 summarizes the catalytic results obtained in the epoxidation of (Z)-
cyclooctene in the presence of MP2 (FeP2, MnP2), MP6 (FeP6, MnP6, and CuP6),
and MP1 (FeP1, MnP1, CuP1). This same table compiles the recycling studies
carried out with the series of insoluble solids MP6.
Page 27 of 49

The catalytic tests confirmed the expected efficiency of MP1 [31,72,76] in the
oxidation of (Z)-cyclooctene. The epoxide yields decreased in the following order:
FeP1 ~ MnP1 > CuP1.
The epoxide yield obtained in the presence of FeP2 was similar to that
observed for FeP1 (Table 2, run 4 versus run 1), which suggested that substitution of
one of the electronegative p-fluorine atom by the bulky MERC group did not affect the
stability of the porphyrin core [5] and still favored the formation of the active catalytic
species [2]. The high stability of FeP2 in solution probably stemmed from the
presence of the acid group, which may have facilitated bi-molecular interactions.
Table 2: (Z)-cyclooctene oxidation by PhIO catalyzed by MPx in
homogeneousa and heterogeneousb media.
Catalyst
Run
Epoxide yield (%)c
FeP1a
MnP1a
CuP1a
FeP2a
FeP6b
1
2
100
98
80
97
75
67
67
63
63
58
3
4
5
FeP6b first reuse
FeP6b second reuse
FeP6b third reuse
FeP6b fourth reuse
FeP6b fifth reuse
6
7
8
9
10
Page 28 of 49

MnP2a
11
12
13
14
15
16
17
18
19
20
21
22
23
24
77
54
56
53
58
56
57
60
55
52
51
50
41
12
MnP6b
MnP6b first reuse
MnP6b second reuse
MnP6b third reuse
MnP6b fourth reuse
MnP6b fifth reuse
CuP6b
CuP6b first reuse
CuP6b second reuse
CuP6b third reuse
CuP6b fourth reuse
CuP6b fifth reuse
PhIOd
a,bThe cyclooctene oxide yield was calculated on the basis of the amount of PhIO
used in each reaction. The catalytic results represent an average of at least
duplicate reactions. MPx/PhIO/(Z)-cyclooctene molar ratio = 1:10:1000. Reaction
time: 1 h. cCyclooctene oxide. dcontrol reaction with no catalyst addition.
The results clearly showed the role that the metal played in the catalytic
efficiency of this series of MPx. For the mono-substituted metalloporphyrin series,
FeP2 performed better than MnP2 (97% versus 77 % epoxide yield, runs 4 and 12,
respectively), which indicated that the iron catalytic species was more stable than the
manganese one.
Page 29 of 49