Oxidative Transformation of a Tetrathia S-Confused Isophlorin into Porphyrin Cation

Article abstract of DOI:10.1021/acs.orglett.7b02317

The synthesis and redox properties of first generation S-confused isophlorins are described. Despite structural resemblance to a confused porphyrin, spectroscopic and computational studies reveal weak paratropic ring current effects in these 20π macrocycles. They display redox properties atypical of parent tetrathia isophlorins. Experimental evidence supports the oxidation of an unstable 19π neutral radical, as a transient intermediate, for the formation of a unique 18π aromatic monocationic species. Spectroscopic and structural characterization revealed the substituent dependent macrocycle oxidation unfamiliar to the chemistry of antiaromatic isophlorinoids.

Full text of DOI:10.1021/acs.orglett.7b02317

Letter
pubs.acs.org/OrgLett
Oxidative Transformation of a Tetrathia S‑Confused Isophlorin into
Porphyrin Cation
Santosh P. Panchal and Venkataramanarao G. Anand*
Department of Chemistry, Indian Institute of Science Education and Research (IISER), Pune 411008, Maharashtra, India
S
* Supporting Information
ABSTRACT: The synthesis and redox properties of first generation S-
confused isophlorins are described. Despite structural resemblance to a
confused porphyrin, spectroscopic and computational studies reveal weak
paratropic ring current effects in these 20π macrocycles. They display
redox properties atypical of parent tetrathia isophlorins. Experimental
evidence supports the oxidation of an unstable 19π neutral radical, as a
transient intermediate, for the formation of a unique 18π aromatic
monocationic species. Spectroscopic and structural characterization
revealed the substituent dependent macrocycle oxidation unfamiliar to
the chemistry of antiaromatic isophlorinoids.
tructural isomers of porphyrin such as N-confused
S
porphyrin1 1 and neo-confused porphyrin2 2 have attracted
significant interest for the synthesis of porphyrinoid organo-
metallic complexes.3 Both 1 and 2 (Figure 1) represent
Figure 2. Illustrative representation of S-confused porphyrin (4a and
4b) and the proposed confused isophlorins (5 and 6).
oxidation by isoelectronic tetrathia porphycene6 illustrates a
solitary report on structure induced altered redox properties in
antiaromatic macrocycles. In this context, we report the
synthesis of a chlorinated derivative of S-confused 20π tetra-
thiaisophlorin 7a with unique redox property to yield an
aromatic porphyrin monocation upon its oxidation.
N-confused porphyrin 1 can be synthesized through a one-
pot synthesis with commercially available precursors such as
pyrrole and aryl aldehyde.7 A similar methodology failed to
yield 5 when thiophene was reacted with pentafluoro
benzaldehyde. Hence, an equimolar ratio of thiophene diol8 8
and a confused trithiophene9 9a were subjected to
condensation reaction in acidic medium under inert conditions
followed by oxidation with FeCl3 in ambient conditions10
(Scheme 1). The reaction mixture was passed through a short
pad of basic alumina and the solvent was evaporated under
reduced pressure. Silica gel column chromatography of the
residue with dichloromethane/n-hexane as eluent led to the
separation of a dark brown solid in 3.8% yields.
Figure 1. Structural illustration for N-confused porphyrin 1, neo-
confused porphyrin 2, and core-modified N-confused porphyrins 3a−
c.
isomeric porphyrin skeletons obtained by swapping the
positions of a carbon and nitrogen in a single pyrrole ring.
Confused porphyrin derivatives 3a−c have also been
synthesized by replacing a pyrrole by other heterocycles such
as thiophene/furan/selenophene to yield core-modified N-
confused porphyrins.4
Latos-Grazynski and co-workers5a reported a confused
porphyrin 4a in which a thiophene ring was inverted similar
to the confused pyrrole of 1. Its oxidation yielded an exocyclic
keto group on the α carbon of the confused thiophene, 4b, with
enhanced aromaticity (Figure 2). A similar observation has
been made with derivatives of N-confused porphyrins.5b,c
Replacing all the pyrrole units by thiophene in 1 should result
in the formation of a confused antiaromatic isophlorin, 5.
Unlike 4a, oxidation of 5 to the corresponding exocyclic CO
should ideally yield a 19π electron radical 6. By virtue of
antiaromatic property, the oxidation of 5 to its corresponding
18π macrocyclic dication, [5]2+ is a potential inhibitor to yield
the macrocyclic radicaloid 6. An apparent resistance to
In its high resolution mass spectrum (see the Supporting
Information, SI), the isolated product displayed an unexpected
Received: July 27, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b02317
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Organic Letters
Letter
and 44°(1)] above and below the mean macrocyclic plane of
the isophlorin. The coplanarity of the other two thiophene
units and a near orthogonal orientation of the meso
pentafluorophenyl rings with the macrocycle invoke a structural
resemblance of 7a to the earlier reported β-substituted tetrathia
isophlorins.11 Unsymmetrical connectivity of the confused
thiophene ring render a decreased macrocyclic symmetry in
comparison to the parent tetrathia isophlorin. This was further
Scheme 1. Synthesis of S-Confused Isophlorins 7a−b, (a)
BF3·OEt2, (b) FeCl3
1
reflected in the H NMR spectrum of 7a recorded at room
temperature (SI). Six of the macrocycle’s seven protons from
the thiophene rings resonate in the region between δ 6.7 to 6.2
ppm. A singlet corresponding to the β-CH, of the inverted
thiophene ring, in the macrocyclic core resonated at δ 9.4 ppm.
A significant downfield chemical shift for this proton is
attributed to the paratropic ring current effect as expected of
the 4nπ systems. However, these chemical shift values suggest
weak paratropic ring current effects in comparison to the
monopyrrole isophlorin.12 An estimated NICS(0)13 value of
+2.6 ppm buttress the feeble antiaromaticity of 7a. A similar 1H
NMR pattern was observed for 7b. This significant loss of
paratropic ring current effect is attributed to the reduced
overlap of π orbitals due to the 2,4 link of the thiophene in the
20π electronic framework. As isophlorin and its expanded
congeners are susceptible to two-electron oxidation,14 it was
envisaged that 7a−b would yield the corresponding 18π
dication upon ring oxidation by appropriate reagents. Meerwein
salt, [Et3O]+[SbCl6]−,15 was added to a dichloromethane
solution of 7a and stirred for 30 min followed by cooling.
The solution was layered with diethyl ether and maintained at
the same temperature for two more hours to yield a green
colored solution suggestive of the expected ring oxidation
(Scheme 2).
m/z value of 1077.8795 (anticipated for 5: C44H8F20S4;
1043.9189).
Its molecular structure determined from single crystal X-ray
diffraction studies (Figure 3a,c) revealed a chlorinated
Figure 3. ORTEP plot of 7a (a,c) and 7b (b,d). Top view (a,b) and
side view (c,d). Solvent molecules, meso substituents and hydrogen
atoms (in side view) are omitted for clarity. Thermal ellipsoids are
drawn at 50% probability.
Scheme 2. Two-Electron Oxidation of 7a to Monocationic
11 Using Meerwein Salt
derivative, 7a, of the expected confused thiophene isophlorin
(C44H7F20S4Cl; 1077.8800) in support of the mass spectro-
metric analysis. The formation of this confused isophlorin, 7a,
was successful only when FeCl3 was employed as the oxidizing
agent. Chlorination of 5 is contrary to the DDQ oxidation of a
similar confused thiophene ring during the synthesis of S-
confused porphyrin.5a Identification of a semiconjugated
macrocycle when DDQ was employed as the oxidizing agent
in the synthesis of 5, was suggestive of an unviable radical 6
(SI). Despite undergoing substitution under reaction con-
ditions 7a was found to be highly stable in ambient atmosphere.
Efforts to dechlorinate 7a to yield the desired 5 were futile. To
prevent the chlorination of confused thiophene ring, a similar
macrocycle was synthesized in 3.3% yields under similar
reaction conditions (SI) with methyl substituted thiophene, 7b.
An m/z value of 1057.9344 (Calcd C45H10F20S4; 1057.9346) in
its HR-MS spectrum established the composition of the
expected isophlorin with a methyl substituent on the confused
thiophene ring and its structure was confirmed from single
crystal X-ray diffraction analysis (Figure 3b,d).
However, mass spectrometric analysis of this green colored
solution displayed an unanticipated m/z value of 1058.9064
(SI). A similar product was identified from mass spectrometric
analysis upon oxidizing 7a by [NO]+[BF4]− and Br2. Usually,
such two-electron ring oxidation display m/2 value for the
dication species. Absence of such evidence strongly suggested a
structural modification to the macrocyclic skeleton upon
oxidation. Cooling the greenish solution to −70 °C yielded
dark green crystals. These crystals were stable under ambient
conditions and subjected to single crystal X-ray diffraction.
Molecular structure obtained from these green crystals revealed
the oxidation of C−Cl bond to CO on the α carbon of the
confused thiophene ring (Figure 4). IR spectrum (SI) of this
macrocycle displayed a carbonyl stretching frequency at
(1690−1650 cm−1) for the observed exocyclic CO in the
confused thiophene ring. This composition (Cald. for
[C44H7F20S4O]+: 1058.9060) of the macrocycle validates the
observed m/z value from mass spectrometry. In addition, the
macrocycle was associated with a [SbCl6]− counteranion,
In both the macrocycles 7a−b inversion of confused
thiophene ring forces the sulfur atom and its adjacent alpha
substitution to the macrocyclic periphery. Structural uniqueness
of 7b is highlighted by tilting of the confused thiophene and its
diagonal partner by [49.0°(9) and 56.7°(7)] on the same side
of the macrocycle. In 7a both, the confused thiophene ring and
its diagonally opposite thiophene ring were tilted by [44°(2)
B
DOI: 10.1021/acs.orglett.7b02317
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Organic Letters
Letter
dicationic species, as observed in expanded isophlorins.
Invariably, their stability within the limited time is sustained
by the absence of reactive functional groups. The distinct
changes in this irreversible redox process were monitored by
electronic spectroscopy (SI). 7a forms brownish colored
solutions in common organic solvents and displays an intense
absorption band at 412 nm (ε = 87 000). Addition of oxidizing
agent at room temperature did not induce any color change.
However, it displayed an uncharacteristic blue-shifted feature-
less absorption at 275 nm suggestive of a cation radical species
[7a]•+. Upon cooling in dry ice acetone bath, the brownish
solution turned green and its absorption was red-shifted by
more than 60 nm compared to 7a. The greenish monocationic
species 11 displayed a typical porphyrin like spectrum with
Soret-like absorption at 475 nm (ε = 67200) followed by low
energy absorptions between 600 and 720 nm. No low energy
absorptions were observed for the 20π isophlorin 7a.
Further support for this understanding came from the
unforeseen resistance of 7b toward two-electron oxidation
under similar conditions. Even though it displays a blue-shifted
featureless absorption (SI) akin to 7a upon oxidation, no
further reaction could be detected over long periods of time
either at room or at low temperatures. Mass spectrometric
analysis did not establish the expected two-electron oxidized
macrocycle, either. These observations establish the formation
of an uncharacteristic cation radical upon oxidation of a
confused isophlorin. Therefore, it can be considered that a
good leaving group, such as Cl−, in the macrocyclic cation
radical reacts with moisture leading to a highly unstable 19π
radical 6 which undergoes subsequent one-electron oxidation to
yield the 18π cationic species 11. The formation of the radical
cation [7a]+• was established through ESR spectroscopy (SI)
upon the addition of Meerwein salt at room temperature.
Hence path B (Scheme 3) seems to be the most appropriate
route for transmutation of 7a to the monocationic species 11.
Cyclic voltammetric studies revealed two irreversible oxidat
ions in support of the two electron oxidation of 7a to 11.
However, no reduction waves were observed for this macro-
cycle.
Figure 4. ORTEP plot of 11 (a) top view and (b) side view. Solvent
molecules, meso substituents and hydrogen atoms (in side view) are
omitted for clarity. Thermal ellipsoids are drawn at 50% probability.
suggesting oxidation of the macrocycle to a monocationic
species, 11.
However, the confused thiophene ring and its diagonally
opposite thiophene ring were found to deviate from the mean
macrocyclic plane by [16.7°(2) and 16.2°(3)] as observed in
1
the parent isophlorin 7a. A well resolved H NMR spectrum
(SI) of 11 recorded at room temperature displayed remarkable
upfield and downfield chemical shift values implying the
significant ring current effects upon oxidation. Even though the
number of signals remained the same as observed for 7a it
distinctly separated the hydrogen of the confused thiophene
ring from the other hydrogens of the macrocycle. Six doublets
corresponding to β-hydrogen atoms of the three normal
thiophene rings resonated in the downfield region between
10.3−9.3 ppm. The cross coupling of these doublets were
confirmed from 1H−1H COSY spectrum (SI). A solitary singlet
for the inner CH resonated at −3.7 ppm to demonstrate
substantial diatropic ring current effects for the oxidized
macrocycle. The calculated NICS(0) value of −12.9 ppm
lend further justification for the aromatic characteristics of 11.
Ring oxidation by two electrons should have ideally yielded 18π
dicationic species, [7a]2+. Isolation of the monocationic species
11 suggested either an unfavorable thermodynamic pathway to
yield [7a]2+ or the kinetic instability of the supposed cation
radical [7a]•+ as an oxidized intermediate.
Hence we could envisage two different pathways (Scheme 3)
for the oxidative transformation of 7a to 11. In path A, we
In summary, we have synthesized the first S-confused
tetrathia isophlorin. Unlike the parent isophlorin, the π circuit
of 20π confused isophlorin enigmatically dampens the
oxidation into its corresponding dication. Yet, it does display
irreversible two one-electron oxidations through atypical
neutral radical intermediate. An exocyclic CO on the
confused thiophene ring transforms the macrocycle into a
neutral and reactive 19π radical species, which is oxidized to an
unusual porphyrin-like monocation.
Scheme 3. Plausible Mechanisms for the Transformation 7a
into 11
a
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b02317.
a
Z = [Et3O]+[SbCl6]− ; X− = [SbCl6]−.
expect the hypothetical dication [7a]2+ to be highly reactive
with ambient moisture, resulting in the formation of 18π
monocation. In path B we suspect the formation of an unstable
monocation radical [7a]•+, which reacts with ambient moisture
to yield the 19π macrocyclic radical 6. Subsequent one-electron
oxidation of 6 should yield the 18π monocation 11. Formation
of a cation radical is a fleeting intermediate for the eventual
Detailed synthetic procedures and spectroscopic charac-
terization of compounds (PDF)
X-ray crystallographic data for compound 7a (CIF)
X-ray crystallographic data for compound 7b (CIF)
X-ray crystallographic data for compound 11 (CIF)
C
DOI: 10.1021/acs.orglett.7b02317
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Organic Letters
Letter
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: vg.anand@iiserpune.ac.in.
ORCID
Venkataramanarao G. Anand: 0000-0002-7110-7994
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
SPP thanks CSIR, New Delhi, India for a research fellowship.
VGA thanks DST, New Delhi, India for the Swarnajayanthi
Fellowship.
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