Synthesis and Studies of Stable Nonaromatic Dithia Pyribenzihexaphyrins

Article abstract of DOI:10.1021/acs.joc.1c00439

We report here one of the rare examples of expanded hexaphyrins named as dithia pyribenzihexaphyrin macrocycles containing six-membered rings such as pyridine and p-phenylene along with five-membered heterocycles such as pyrrole and thiophene as a part of a macrocyclic frame. Trifluoroacetic acid catalyzed [3 + 3] condensation of equimolar mixture of [10,10′-bis(p-tert-butyl phenyl)hydroxymethyl]-1,3-bis(2-thienyl)pyridine diol (2,6-pyri diol) and 1,4-bis(phenyl(1H-pyrrol-2-yl)methyl)benzene (p-benzidipyrrane) in CH2Cl2 followed by oxidation with DDQ afforded stable nonaromatic dithia 2,6-pyri-para-benzihexapyrins 1 and 2 in 6-8% yields. The macrocycles were characterized by high-resolution mass spectroscopy and 1D and 2D NMR spectroscopy. NMR studies revealed the nonaromatic nature of dithia 2,6-pyri-p-benzihexaphyrins and indicated that the para-phenylene ring prefers to be in quininoid form rather than in benzenoid form. The macrocycles displayed sharp absorption bands in the region of ～380-500 nm and a broad band at ～700 nm, reflecting their nonaromatic nature. Upon protonation, these macrocycles showed NIR absorption properties. The redox studies of macrocycles indicated their electron-deficient nature. The DFT/TD-DFT studies are in line with the experimental observations.

Full text of DOI:10.1021/acs.joc.1c00439

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Synthesis and Studies of Stable Nonaromatic Dithia
Pyribenzihexaphyrins
Nisha Rawat, Avisikta Sinha, Dijo Prasannan, and Mangalampalli Ravikanth*
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ABSTRACT: We report here one of the rare examples of
expanded hexaphyrins named as dithia pyribenzihexaphyrin
macrocycles containing six-membered rings such as pyridine and
p-phenylene along with five-membered heterocycles such as pyrrole
and thiophene as a part of a macrocyclic frame. Trifluoroacetic acid
catalyzed [3 + 3] condensation of equimolar mixture of [10,10′-
bis(p-tert-butyl phenyl)hydroxymethyl]-1,3-bis(2-thienyl)pyridine
diol (2,6-pyri diol) and 1,4-bis(phenyl(1H-pyrrol-2-yl)methyl)-
benzene (p-benzidipyrrane) in CH2Cl2 followed by oxidation with
DDQ afforded stable nonaromatic dithia 2,6-pyri-para-benzihex-
apyrins 1 and 2 in 6−8% yields. The macrocycles were
characterized by high-resolution mass spectroscopy and 1D and
2D NMR spectroscopy. NMR studies revealed the nonaromatic nature of dithia 2,6-pyri-p-benzihexaphyrins and indicated that the
para-phenylene ring prefers to be in quininoid form rather than in benzenoid form. The macrocycles displayed sharp absorption
bands in the region of ∼380−500 nm and a broad band at ∼700 nm, reflecting their nonaromatic nature. Upon protonation, these
macrocycles showed NIR absorption properties. The redox studies of macrocycles indicated their electron-deficient nature. The
DFT/TD-DFT studies are in line with the experimental observations.
delocalization of electrons with the rest of the porphyrin
system, whereas, in p-benziporphyrins, the p-phenylene unit
participates in the π-delocalization with the rest of the
porphyrin system. Lash’s1,2,9,21,22b and Latos-Grazynski’-
s5−8,11,12,22a research groups and others10,12,17,19,20,23,24 have
extensively investigated the synthesis, properties, and coordi-
nation chemistry of m- and p-benziporphyrins. However, the
reports on benzene-containing expanded porphyrinoids are
relatively few to understand their physico-chemical and
coordination properties.5,6,9,12,16−20,24,25 The expanded m-
benziporphyrinoid such as 1 was synthesized over a sequence
of steps and showed its ability to act as a ligand to form
organometallic complexes24 (Chart 1).
We recently reported the synthesis of stable nonaromatic
[28π] dithia m-benzihexaphyrins (1.0.0.1.1.1) 2 and explored
their spectral and redox properties.16 We also reported the
synthesis of pyridine analogue of dithia m-benzihexaphyrins
such as macrocycle 3 by replacing the benzene ring of dithia m-
benzihexaphyrins 2 with 2,6-pyridine ring.26 During the course
INTRODUCTION
■
One of the most attractive modifications of porphyrinoids is
the replacement of five-membered pyrrole ring(s) with six-
membered benzene, and the resulted benziporphyrinoids are
known to exhibit intriguing spectroscopic, structural, and
chemical properties.1−5 Benziporphyrinoids can form stable
organometallic complexes and have been shown to have
applications in various fields including the development of
chemical sensors and molecular recognition studies.6−8 The
characteristics of benziporphyrinoids may vary from non-
aromatic9,10 to highly aromatic5 systems, and in a few cases,
antiaromatic11,12 structures are formed. Thus, benziporphyr-
inoids received a lot of attention since the aromaticity of these
systems has several interesting aspects, and most notably, di-p-
benzihexaphyrin is the first example of a Huckel−Mobius
aromaticity switch.12−15 In benziporphyrinoids, the benzene
unit is connected with the rest of the porphyrinoid system
either via its 1,3-positions10,16 (meta-benziporphyrinoids) or
1,4-positions5,12,17,18 (para-benziporphyrinoids). The proper-
ties of m-benziporphyrinoids and p-benziporphyrinoids are
very different from each other.3,6 The studies indicated that
simple m-benziporphyrins are nonaromatic but can be
converted into aromatic systems by suitable modifications/
substitutions on the m-phenylene subunit,19 whereas p-
benziporphyrins exhibit diatropic ring current and show
more aromatic features.20 This is because, in m-benziporphyr-
ins, the m-phenylene unit does not participate in the π
Received: February 22, 2021
Published: April 26, 2021
https://doi.org/10.1021/acs.joc.1c00439
© 2021 American Chemical Society
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Chart 1. Structures of Benzihexaphyrin Analogues
Scheme 1. Synthesis of 2,6-Pyri-dithia-p-benzihexaphyrins 4 and 5
of this chemistry, we realized that it is interesting to synthesize
hexaphyrins in which both benzene and pyridine units are part
of the macrocyclic framework along with other five-membered
heterocycles. The macrocycles consisting of different five and
six membered heterocycles as a part of macrocyclic framework
are very useful as ligands for selective formation of complexes
with guest molecules, anions, or metal ions besides their
potential applications in fields such as NIR dyes, magnetic
there is only one report on porphyrinoid that contains both
pyridine and m-phenylene rings along with other five-
membered heterocycles as a part of the macrocyclic frame-
work.31 Herein, we report our successful synthesis of two
examples of pyridine-incorporated dithia 2,6-pyri-p-benzihex-
aphyrins 4 and 5 (Chart 1) under [3 + 3] condensation
reaction conditions using readily available precursors. Although
macrocycles 4 and 5 are quite stable, our attempts failed when
we used the other meso-aryl substituents such as anisyl, 2,4,6-
trimethylphenyl groups adjacent to the para-phenylene
materials, nonlinear optical materials, and so on.21,23,27−30
perusal of literature revealed that, to the best of our knowledge,
A
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1
Figure 1. Comparison of H NMR spectra of compounds 3 and 4 in CDCl3 at room temperature (25 °C).
moiety20 of hexaphyrin macrocycle. Our attempts to prepare
the analogous dithia pyri m-benziporphyrins 6 were also
unsuccessful because of their inherent unstable nature. Thus,
the dithia 2,6-pyri-p-benzihexaphyrins 4 and 5 reported here
are the only stable macrocycles that contain both pyridine and
p-phenylene rings in their macrocyclic framework and
thoroughly characterized by 1D and 2D NMR, absorption,
electrochemical, and density functional theory (DFT) studies.
Our studies supported the nonaromatic nature of dithia 2,6-
pyri-p-benzihexaphyrins 4 and 5 like macrocycle 3. However,
the electronic properties are quite altered when the pyrrole
ring of macrocycle 3 was replaced with p-phenylene ring in
macrocycles 4 and 5 as reflected from their spectral and
electrochemical properties.
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in open air
for 30 min at room temperature. The TLC analysis showed
only one major spot corresponding to the desired macrocycles
4/5 as judged by high-resolution mass spectroscopy (HR-MS)
analysis. The crude reaction mixture after the removal of the
solvent was column chromatographed on basic alumina using
petroleum ether/ethyl acetate (85:15) as an eluent to yield
dithia 2,6-pyri-p-benzihexaphyrins, 4 and 5, as green solids in
6−8% yields (Scheme 1). The reaction conditions were varied
with different equivalents of TFA, BF3·OEt2, and PTSA.
However, no significant improvement of the yields of the dithia
2,6-pyri-p-benzihexaphyrins 4 and 5 were observed. Further-
more, when we used other meso-aryl-substituted p-benzidi-
pyrranes such as anisyl and 2,4,6-trimethylphenyl-substituted
p-benzidipyrranes for [3 + 3] condensation with m-pyri diol 8
under similar reaction conditions, the stable dithia 2,6-pyri-p-
benzihexaphyrins were not formed. We also attempted the [3 +
3] condensation of 2,6-pyri diol 8 with m-benzidipyrranes 10a/
10b under various reaction conditions but failed to obtain
dithia 2,6-pyri-m-benzihexaphyrins 6 because of the inherent
unstable nature of macrocycles. Both the macrocycles 4 and 5
were freely soluble in common organic solvents. The formation
of 2,6-pyri-dithia-p-benzihexaphyrins 4 and 5 was initially
confirmed by the corresponding molecular ion in the HR-MS
(Figures S4 and S7).
RESULTS AND DISCUSSION
■
The target macrocycles 4 and 5 were synthesized as shown in
Scheme 1. The desired precursor, 10,10′-bis(p-tert-butyl
phenyl)hydroxymethyl]-1,3-bis(2-thienyl)pyridine diol26 (2,6-
pyri diol) 8 (Figures S1−S3), was prepared in two steps
starting with commercially available 2,6-dibromopyridine.
Suzuki coupling of 2,6-dibromopyridine with 4 equiv of 2-
thiophene boronic acid afforded 2,6-bis(dithienyl)pyridine 7.
The compound 7 was treated with n-BuLi in THF, followed by
4-tert-butylbenzaldehyde, and column chromatographic purifi-
cation yielded 2,6-pyri diol 8 in 72% yield. The other
precursors, 1,4-bis(aryl(1H-pyrrol-2-yl)methyl)benzene (p-
benzidipyrrane) 9a/9b and 1,3-bis(aryl(1H-pyrrol-2-yl)-
methyl)benzene (m-benzidipyrrane) 10a/10b, were synthe-
sized by following the reported synthetic procedures.20 The
2,6-pyridine-incorporated dithia 2,6-pyri-p-benzihexaphyrins 4
and 5 were synthesized by the [3 + 3] condensation of
equimolar mixture of 2,6-pyri diol 8 and appropriate p-
benzidipyrrane, 9a/9b, in the presence of 1 equiv of
trifluoroacetic acid (TFA) in dichloromethane under an inert
atmosphere for 1.5 h, followed by oxidation with 2.5 equiv of
The 1D and 2D NMR spectroscopic techniques were used
to characterize the 2,6-pyri-dithia-p-benzihexaphyrins 4 and 5.
1
Figure 1 displays the comparison of the partial H NMR
spectrum of compounds 4 and 3. All the resonances with
1
integrated intensities in the H NMR spectra of 4 and 5 were
identified and assigned based on their location, integration,
coupling constants, and proton−proton correlations observed
1
1
in H−1H COSY and H−1H NOESY NMR spectra (Figures
S11 and S12, respectively). The number of resonances in the
1H NMR spectra of macrocycles 4 and 5 is exactly the same as
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Table 1. Comparison of H NMR, Absorption, and Electrochemical Data of Compounds 4 and 5 with 3
1H NMR (δ in pm)
λabs, nm (log εmax
)
reduction (V)
oxidation (V)
compound
2,6-pyridine type a
protons type b
8.43
(I)
(II)
(III)
(I)
(II)
(I)
(II)
(III)
1.38
3
8.13
8.05
8.06
406 (4.2)
439 (4.4)
385 (4.7)
337 (4.6)
390 (4.7)
348 (4.5)
496 (4.5)
540 (4.5)
492 (4.8)
483 (4.7)
492 (4.8)
484 (4.6)
813 (4.0)
990 (4.0)
707 (4.2)
1037 (3.8)
706 (4.2)
1040 (4.2)
−0.61
−0.92
−0.76
−0.71
0.70
1.14
3.2H2+
4
7.93
7.93
−0.54
−0.50
0.80
0.80
0.99
1.10
1.24
1.26
4.2H2+
5
5.2H2+
Figure 2. (a) Comparison of the normalized absorption spectra of compounds 3 and 4 in CHCl3, (b) comparison of the normalized absorption
spectra of compounds 3.2H2+ and 4.2H2+ recorded in CHCl3, (c) change in the absorption spectra of 1 (1 × 10−5 M) upon the systematic addition
of (1 × 10−3 M) TFA (0−10 equiv) recorded in CHCl3, and (d) comparison of cyclic voltammogram (red and blue solid lines) of compounds 3
and 4, respectively, and differential pulse voltammograms (dotted black lines) recorded in dry dichloromethane with 0.1 M TBAP as a supporting
electrolyte and a saturated calomel electrode (SCE) as the reference electrode at a scan rate of 50 mV/s.
expected on the basis of their molecular structures and
symmetric nature.
cross-peak correlation with the type n protons resonance at
7.24 ppm. The H NMR spectrum revealed the presence of
1
All the proton resonances for pyrrole, thiophene, pyridine,
and benzene moieties in the macrocycle 4 appeared in the
region of 6.40−8.05 ppm, indicating the nonaromatic nature16
of compound 4. The triplet at 7.91 ppm due to type a protons
on the 2,6-pyridine ring of the macrocycle 4 showed cross-peak
correlation with type b protons of the 2,6-pyridine ring protons
at 8.05 ppm which appeared as a doublet. The pyridine type b
protons showed NOE correlation with the doublet at 7.76
ppm, which was due to type c protons of the thiophene ring.
The type c protons are cross-peak correlated with type d
protons resonance at 7.24 ppm, confirming the type c and type
d protons of the thiophene ring. The type d protons at 7.24
ppm of the thiophene ring show NOE correlation with type p
protons of the tert-butyl phenyl ring at 7.50 ppm. The type p
(7.50 ppm) protons are NOE correlated with type e protons of
pyrrole ring resonance at 6.93 ppm which in turn is cross-peak
correlated with type f proton resonance at 6.38 ppm. The type
f protons at 6.38 ppm are NOE correlated with type m proton
resonance at 7.37 ppm of the tolyl group which in turn was in
two types of protons for the benzene ring. The inner protons,
type h appeared as a doublet at 6.93 ppm, and are more upfield
than the outer protons type g, which appeared as a singlet at
7.62 ppm. The type m proton showed NOE correlation with
type g and type h protons clearly confirming the structure. The
absence of a −NH proton also reveals that the macrocycle has
a structure with a “quinonoid” form rather than benzenoid. To
understand the alteration in electronic properties when the
pyrrole ring in macrocycle 3 is replaced with the p-phenylene
1
ring in macrocycle 4, we compared the H NMR spectra of
macrocycle 3 and 4 in the selected region as shown in Figure 1.
As clear from the Figure 1, all the outer ring protons of
macrocycle 4 experienced upfield shifts compared to macro-
cycle 3. For example, the pyridine protons (type a and type b)
which appeared as resonances at 8.13 and 8.43 ppm in
macrocycle 3 experienced upfield shifts in macrocycle 4 and
appeared at 7.93 and 8.05 ppm, respectively. Similarly, the
pyrrole ring protons (type e and type f) which appeared at 7.07
and 6.82 ppm in macrocycle 3 were upfield shifted to 6.93 and
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Figure 3. Optimized geometries of compound 4: (a) top view and (b) side view; compound 3: (c) top view and (d) side view. The phenyl rings
are omitted for clarity in the side view.
6.38 ppm, respectively, in macrocycle 4. The thiophene
protons (type c and type d) also shifted to upfield in
macrocycle 4 compared to macrocycle 3. All these changes in
the chemical shifts of various protons of macrocycle clearly
supports the alteration in ring current upon replacing the five-
membered pyrrole ring in macrocycle 3 with six-membered p-
phenylene ring in macrocycle 4.
macrocycle 4.2H2+, the peak intensity at 385 nm was decreased
and blue-shifted to 337 nm; the intensity of the peak at 492 nm
was also decreased and blue-sifted to 483 nm along with the
appearance of a new shoulder band at 443 nm and the peak at
707 nm was diminished gradually and a new broad band
appeared in the NIR region with peak maxima at 1037 nm
along with two clear isosbestic points at 597 and 820 nm
supporting the formation of protonated macrocycle 4.2H2+.
The redox properties of compounds 4 and 5 along with 3
were probed using cyclic and differential pulse voltammetry
(DPV) at a scan rate of 50 mV/s using tetra-n-butylammonium
perchlorate as the supporting electrolyte and SCE as the
reference electrode (Figure S15). All the potentials were
calibrated by using ferrocene as an external standard and
comparison of reduction waves of compound 3 and 4 is shown
in Figure 2d. Similar to recently reported dithia 2,6-
pyrihexaphyrin 3,26 the compound 4 showed three irreversible
oxidations (0.80, 0.99, and 1.24 V) and two reversible
reduction peaks at −0.76 and −0.54 V (Table 1). Thus, the
redox data indicates that the macrocycles 4 and 5 were easier
to reduce than that of previously reported dithia 2,6-
pyrihexaphyrin26 3 (−0.92 and −0.61 V) supporting their
electron-deficient nature.
Theoretical Studies. The ground-state geometry opti-
mization at the DFT level and nucleus-independent chemical
shifts (NICS)32 calculations for compound 4 were performed
by using the B3LYP/6-31G (d, p) level to probe into the
structural, spectral, and the electrochemical properties. Figure
3 presents the optimized geometries of the macrocycles 3 and
4. It is clearly visible from Figure 3 that the macrocycles 3 and
4 adopt a highly distorted saddle-shaped conformation. This
feature supports the nonplanar geometry of macrocycles 3 and
4. The highly contorted structure of macrocycle 4 was very
well evident from the angle of deviations of the heterocycle and
benzene rings present inside the macrocyclic core. In
macrocycle 4, the pyridine unit (ring a) was found to be
Absorption and Electrochemical Properties. The
absorption spectra of macrocycles 4 and 5 and their
protonated derivatives 4.2H2+ and 5.2H2+ were recorded in
chloroform and compared with macrocycle 3 and its
protonated derivative 3.2H2+ (Table 1). The comparison of
absorption spectra of 3 and 4 is presented in Figure 2a and the
protonated derivatives 3.2H2+ and 4.2H2+ in Figure 2b (Table
1). Due to their nonaromatic characteristic, 2,6-pyri-dithia-p-
benzihexaphyrins 4 and 5 showed two sharp absorptions in the
region of 380−500 nm and a broad band at ∼700 nm (Figure
2). The absorption spectral pattern of macrocycles 4 and 5
resembles closely to that of dithia 2,6-pyrihexaphyrin macro-
cycle26 3 with changes in their peak maxima. Upon
protonation of macrocycles 4 and 5 with TFA, the intensity
of the broad band at ∼700 nm was decreased along with the
appearance of a new broad band at 1030 nm due to the
formation of protonated derivatives 4.2H2+ and 5.2H2+. These
absorption features were also similar to that of the protonated
derivative 3.2H2+ with significant shifts in their absorption
peak maxima.26 All these absorption spectral shifts support the
alteration of electronic properties in dithia 2,6-pyri-p-
benzihexaphyrins 4 and 5 compared to dithia 2,6-pyrihex-
aphyrin 3.
We also carried out the systematic protonation studies by
the addition of increasing equivalents of TFA to macrocycle 4
in CHCl3 as shown in Figure 2c. Upon increasing addition of
TFA (0−10 equiv) to compound 4 in chloroform, the color of
the solution was changed from green to red due to the
formation of protonated macrocycle 4.2H2+. In protonated
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deviated by an angle of 50.02° w.r.t the “mean plane” defined
by the four meso carbon atoms (C9, C14, C21, and C26). The
two thiophene rings (ring b and ring c) connected at the 2,5
position of “ring a” exhibits almost a similar magnitude of
deviation wherein the thiophene ring (ring b) bends away from
the “mean plane” by an angle of 35.55° and the other
thiophene ring (ring c) by an angle of 36.26° (Table 2). A
located at a distance of 3.121 Å which is greater than that
observed for macrocycle 4. Similarly, the nitrogen atoms of the
pyrrole rings N2, N3, and N4 were also deviated to a greater
extent in macrocycle 3, which further supports the enhanced
nonplanarity and distortion of macrocycle 3 compared to
macrocycle 4.
The close bond length analysis indicates that the C16−C17
(1.365 Å) and C19−C20 (1.359 Å) bond lengths of the p-
phenylene ring (f) were relatively shorter as opposed to those
of C15−C16, C17−C18, C18−C19, and C20−C15 (1.446
0.02 Å), which displayed almost a single-bond characteristic.
This feature of nonequivalent bond lengths in the p-phenylene
ring of macrocycle 4 is very much unlike free benzene which
shows identical bond lengths (1.40 Å). These values clearly
indicate that the double bond characteristic exists between
C16−C17 and C19−C20, whereas C15−C16, C17−C18,
C18−C19, and C20−C15 are nearly single bond in nature.
However, the C−C and C−N bond lengths in pyridine (ring
a) and pyrrole (ring d and ring e) in macrocycle 4 were
comparable to the bond lengths in free pyrrole and pyridine.
The bond length equalization of the p-phenylene ring is one of
the parameters that defines its aromaticity. Thus, the absence
of equal bond length of the p-phenylene ring inside the
macrocyclic core clearly highlights its nonaromatic character-
istic. On the contrary, for macrocycle 3, the C−C and C−N
bond lengths of the pyrrole moiety (rings d, e, and f) were
slightly elongated as compared to free pyrrole, whereas for the
pyridine ring, the bond lengths were almost comparable.
The analysis of the selected Frontier molecular orbital
reveals that for compound 4, the highest occupied molecular
orbital (HOMO) represents nonuniform distribution of orbital
density, which is mostly focused on the benzidipyrrane moiety
with very less orbital density on the meso substituents, whereas
lowest unoccupied molecular orbital (LUMO) presents a very
uniform distribution of orbital density throughout the
macrocyclic framework, leaving no electron density on the
meso aryl substituents. Figure 4 illustrates the comparison of
orbital energies of HOMO and LUMO along with their band
gap (expressed in eV) for macrocycles 3 and 4. Macrocycle 3
also exhibits similar orbital density distribution in HOMO and
Table 2. Comparison of Various Bond Angles
deviation from the mean plane compound 3 (deg) compound 4 (deg)
ring a
ring b
ring c
ring d
ring e
ring f
51.28
46.13
52.45
41.43
56.58
24.18
50.02
35.55
36.26
34.38
35.41
18.6
similar trend in the angle of deviation was displayed by the two
pyrrole rings (ring d and e) which were oriented below the
“mean plane”. Among all the rings which were a part of the
macrocycle, the deviation exerted by the phenylene ring (ring
f) was found to be the least (18.6°).
In macrocycle 3, where the five-membered pyrrole ring (ring
f) is present in the place of a six-membered phenylene ring
(ring f), the overall distortion in the macrocycle markedly
increases which is reflected in the increased angle deviation of
all the rings w.r.t the “mean plane” defined by the four meso
carbon atoms (C9, C14, C19, and C24) (Table 2). The
pyrrole ring (ring f) was deviated by an angle of 24° w.r.t
“mean plane” as a result of which the benzidipyrrane half of the
molecule adopts an oval shape. The nitrogen atoms (N2 and
N3) of the pyrrole ring in the macrocycle 4 were situated at a
distance of 0.138 Å and 0.131 Å, respectively, whereas the
nitrogen atom (N1) of the pyridine ring was placed at a
distance of 2.280 Å from the “mean plane”. The sulfur atoms of
the thiophene rings were located at a distance of 1.205 Å,
whereas the C atoms of the benzene ring (ring f) displayed
little to almost no deviation (0.679−0.89 Å). On the other
hand, in macrocycle 3, the N atom of the pyridine ring was
Figure 4. (a) Energy-level diagram (selected FMOs) of compounds 4 and 3 calculated by the B3LYP/6−31g(d, p) method and (b) calculated
excitations (blue vertical lines) and experimental UV/vis absorption spectra (black line) for compound 4 (ε in M−1 cm−1).
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LUMO to macrocycle 4. The very even distribution of orbital
density throughout the macrocyclic core over the heterocyclic
and p-phenylene rings for compound 4 via the meso sp2 carbon
atoms support the effective π overlap along the predicted
conjugation pathway.
As clearly shown in Figure 4, the presence of a six-
membered p-phenylene ring in the place of a five-membered
pyrrole ring in macrocycle 4 stabilizes the LUMO because of
which the HOMO−LUMO band gap also undergoes a notable
decrease from ΔE = 1.8053 eV in macrocycle26 3 to ΔE =
1.5367 eV in macrocycle 4, but both these macrocycles show
comparable absorption features. The HOMO−LUMO gap
(1.5367 eV) in macrocycle 4 matches well with the
experimentally computed value from the cyclic voltammetric
study (Table S1). Thus, the spectral and electrochemical
properties predicted by DFT are consistent with the
experimental data.
that for rings consisting of localized single and double bonds,
very small and negative HOMA values are obtained, suggesting
its nonaromatic nature.38,39
Thus, the spectral and electrochemical properties predicted
by DFT agreed closely with the experimental data. In short, the
absence of bond length equalization, low-field 1H NMR shifts,
small NICS values, and nonplanar structure40 undoubtedly
supports the nonaromatic nature of macrocycle 4.
CONCLUSIONS
■
In summary, we have successfully synthesized the stable
nonaromatic 2,6-pyri-dithia-p-benzihexaphyrins 4 and 5 using-
[3 + 3] condensation reaction with the readily available
precursors. To the best of our knowledge, compounds 4 and 5
represent one of the limited examples of the pyridine-
incorporated dithia para-benzihexaphyrins. The nonaromatic
features of the macrocycles were revealed by absorption and
NMR studies. The experimental results were further supported
by DFT studies. We anticipate that the presence of pyridine/
pyrrole nitrogens, p-phenylene carbons, and thiophene sulfurs
would help to form interesting coordination compounds and
such studies are underway.
Furthermore, the TD-DFT studies were also performed to
predict the oscillator strength and excitation energies of the
first S0−Sn transitions. The calculated vertical excitation
energies for macrocycle 4 fairly matched with their respective
experimental data both in position and in relative intensity. In
the case of compound 4 (Figure 4b), the absorption/
excitations around the region of 390−410 and ∼500 nm
with large oscillator strengths originating mainly from HOMO
− 1 → LUMO + 1 and HOMO − 1 → LUMO transitions,
respectively, while the broad band of low intensity in the
region of 700−900 nm arises from the HOMO → LUMO
transition. However, for macrocycle26 3, the HOMO →
LUMO + 2 transitions were responsible for the sharp intense
band around 410 nm and the low energy charge transfer band
was mainly a consequence of the HOMO → LUMO
transitions. Upon protonation, the HOMO−LUMO band
gap for both the compounds 3.2H2+ and 4.2H2+ showed a
significant decrease in energy (ΔE = 1.2263 eV for 4.2H2+ and
1.4829 eV for 3.2H2+) as compared to their corresponding free
bases 4 and 3, respectively, which justifies the observed
bathochromic shifts in the absorption spectra (Figure S18).
The 1H chemical shifts of compound 4 were simulated using
the gauge-including atomic orbital method at the B3LYP/6-
EXPERIMENTAL SECTION
■
General Experimental Section. All the chemicals used for the
synthesis were of reagent grade unless otherwise specified. Boron
trifluoride diethyl etherate (BF3·OEt2), TFA, and 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone (DDQ) obtained from Sigma-Aldrich were
used as such. All other chemicals used for the synthesis were of
reagent grade unless otherwise specified. The 2,6-pyri diol 8 (10,10′-
Bis[4-(tert-butyl)phenyl]-1,3-bis(2-thienyl)-pyridinediol) was pre-
pared by following our reported procedure.26 Solvents such as
petroleum ether (60−80 °C), ethyl acetate, and dichloromethane
purchased from Merck, India, were used without further purification.
Column chromatography was performed on basic alumina (80−200
mesh). 1H (1D and 2D) and 13C{1H} NMR spectra were recorded on
a Bruker 400 and 500 MHz FT-NMR spectrometer in CDCl3 using
tetramethylsilane as the internal reference. The 13C{1H} NMR
frequencies are 125.77 and 100.06 MHz for 500 and 400 MHz
instruments, respectively. Structural assignments were made with
additional information from 1H−1H COSY and 1H−1H NOESY
experiments. The high-resolution mass spectroscopy (HR-MS)
spectra were recorded with a Bruker maXis Impact and QTof micro
mass spectrometer using positive mode ESI methods in acetonitrile or
methanol. UV−visible absorption spectra were recorded on a Cary
Series UV−vis−NIR and a UV 3600 Shimadzu spectrophotometer.
The stock solutions of the compounds (5 × 10−4 M) were prepared
using HPLC-grade chloroform. Cyclic voltammetric studies were
carried out with a BAS electrochemical system utilizing the three-
electrode configuration consisting of glassy carbon (working
electrode), platinum wire (auxiliary electrode), and saturated calomel
(reference electrode) electrodes. The concentrations of the samples
were maintained as 0.01 M containing tetrabutylammonium
perchlorate (TBAP) as the supporting electrolyte (0.1 M) in
dichloromethane at 25 °C under an argon atmosphere at a scan
rate of 50 mV/s. The half-wave potentials measured using DPV were
calculated manually by taking the average of the cathodic and anodic
peak potentials. All the potentials were calibrated by using ferrocene
as an external standard, taking E1/2 (Fc/Fc+) = 0.42 V versus SCE.
All the theoretical calculations utilized 6-31g(d,p) level of theory
and were performed using the Gaussian09 package. The ground-state
geometry optimization, NICS,32 and AICD calculations for the
compounds 4 and 5 were performed at the DFT level using Becke’s
three-parameter functional combined with the Lee−Yang−Parr
exchange correlation functional (B3LYP).
1
311G(d,p) level. The H chemical shift values were calculated
with reference to CHCl3 (7.26 ppm). The simulated 1H NMR
was qualitatively in good agreement with the experimentally
recorded 1H NMR spectrum in CDCl3 (Figure 1). The
experimental and theoretical chemical shifts are presented in
the Supporting Information (Tables S2 and S3), for example,
the para-phenylene protons of macrocycle 4, the type h and
type g observed at 6.93 and 7.62 ppm in the 1H NMR
spectrum appeared at 7.03 and 7.26, respectively, in the
theoretically computed spectrum.
For the quantitative evaluation of aromaticity, the NICS33
and harmonic oscillator model of aromaticity (HOMA)34
values were calculated for macrocycle 4. The isotropic NICS
(NICS(0)iso) and the zz component of the shielding tensor
(NICS(0)zz) values in the S0 state for the compound 4 are
−0.6220 and +4.5369, respectively, suggesting its nonaromatic
nature.35−38 Thus, the molecule lacks both local and ground-
state global aromaticity. The HOMA indices were calculated39
along various π-conjugation paths using the optimized
structure for macrocycle 4. The HOMA factor is 0 for a
model nonaromatic ring and 1 for a system where there is
complete delocalization. The HOMA values of macrocycle 4
range from −0.26 to 0.47 (Figure S19). It has been reported
Compound 4. To a solution of 1,3-bis(2-thienyl)-pyridinediol26
(100 mg, 0.176 mmol) and 1,4-bis(p-tolyl(2-pyrolyl)methyl)
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The Journal of Organic Chemistry
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Article
benzene20 (73.36 mg, 0.176 mmol) dissolved in 200 mL of CH2Cl2
under an inert atmosphere, TFA (13 μL, 0.176 mmol) was added and
stirred for 1.5 h. DDQ (99.95 mg, 0.440 mmol) was then added to the
reaction mixture and stirred for an additional 0.5 h in open air. The
solvent was removed under reduced pressure, and the crude
compound was subjected to basic alumina column chromatography.
The desired product was isolated using petroleum ether/ethyl acetate
(85:15) as a green solid in 8% yield (14 mg); mp > 300 °C; 1H NMR
(400 MHz, CDCl3): δ 8.05 (d, J = 7.8 Hz, 2H), 7.93 (t, 1H), 7.76 (d,
J = 4.2 Hz, 2H), 7.62 (s, 2H), 7.50 (s, 8H), 7.37 (d, J = 7.9 Hz, 4H),
7.24 (d, J = 4.2 Hz, 6H), 6.93 (d, J = 4.5 Hz, 4H), 6.38 (d, J = 4.6 Hz,
2H), 2.44 (s, 6H), 1.42 (s, 18H); 13C{1H} NMR (101 MHz, CDCl3):
δ 169.6, 154.5, 153.5, 151.9, 144.2, 142.5, 138.4, 137.6, 137.1, 137.0,
135.7, 134.2, 132.6, 132.1, 131.7, 130.9, 129.7, 128.5, 126.0, 125.2,
124.5, 118.16, 34.8, 31.4, 21.4; UV−vis: CHCl3, λmax/nm (log ε)
385(4.7), 492(4.8), 707(4.2); HR-MS (ESI-TOF) m/z: [M + H]+
calcd for C65H56N3S2, 942.3919; found, 942.3910.
(2) Lash, T. D. Benziporphyrins, a Unique Platform for Exploring
the Aromatic Characteristics of Porphyrinoid Systems. Org. Biomol.
Chem. 2015, 13, 7846−7878.
́ ́
(3) Step̧ ien, M.; Latos-Grazynski, L. Benziporphyrins: Exploring
Arene Chemistry in a Macrocyclic Environment. Acc. Chem. Res.
2005, 38, 88−98.
(4) Lash, T. D. Carbaporphyrinoid Systems. Chem. Rev. 2017, 117,
2313−2446.
́ ́
(5) Step̧ ien, M.; Latos-Grazynski, L. Tetraphenyl-p-Benziporphyrin:
A Carbaporphyrinoid with Two Linked Carbon Atoms in the
Coordination Core. J. Am. Chem. Soc. 2002, 124, 3838−3839.
́ ́
(6) Step̧ ien, M.; Latos-Grazynski, L.; Szterenberg, L.; Panek, J.;
Latajka, Z. Cadmium(II) and Nickel(II) Complexes of Benziporphyr-
ins. A Study of Weak Intramolecular Metal-Arene Interactions. J. Am.
Chem. Soc. 2004, 126, 4566−4580.
́
(7) Idec, A.; Pawlicki, M.; Latos-Grazynski, L. Ruthenium(II) and
̇
Ruthenium(III) Complexes of p-Benziporphyrin: Merging Equatorial
and Axial Organometallic Coordination. Inorg. Chem. 2017, 56,
10337−10352.
Compound 5. Green solid. Yield 6% (10 mg)); mp > 300 °C; 1H
NMR (400 MHz, CDCl3): δ 8.06 (d, J = 7.8 Hz, 2H), 7.93 (t, 1H),
7.77 (d, J = 4.1 Hz, 2H), 7.67 (s, 2H), 7.50 (s, 8H), 7.47−7.40 (m,
10H), 7.25 (d, 2H), 6.95−6.87 (m, 4H), 6.35 (d, J = 4.6 Hz, 2H),
1.42 (s, 18H); 13C{1H} NMR (101 MHz, CDCl3): δ 169.4, 154.5,
153.6, 151.9, 151.5, 144.1, 142.8, 141.4, 137.0, 136.3, 135.8, 135.4,
134.3, 132.4, 132.1, 131.6, 130.9, 127.9, 127.7, 125.3, 124.5, 118.2,
34.8, 31.4; UV−vis: CHCl3, λmax/nm (log ε) 390(4.7), 492(4.8), 706
(4.2); HR-MS (ESI-TOF) m/z: [M + H]+ calcd for C63H52N3S2,
914.3597; found, 914.3592.
́
(8) Hurej, K.; Pawlicki, M.; Latos-Grazynski, L. Rhodium-Induced
̇
Reversible C−C Bond Cleavage: Transformations of Rhodium(III)
22-Alkyl-m -benziporphyrins. Chem.Eur. J. 2018, 24, 115−126.
(9) Lash, T. D.; Toney, A. M.; Castans, K. M.; Ferrence, G. M.
Synthesis of Benziporphyrins and Heterobenziporphyrins and an
Assessment of the Diatropic Characteristics of the Protonated Species.
J. Org. Chem. 2013, 78, 9143−9152.
(10) Berlin, K.; Breitmaier, E. Benziporphyrin, a Benzene-
Containing, Nonaromatic Porphyrin Analogue. Angew. Chem., Int.
Ed. Engl. 1994, 33, 1246−1247.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00439.
■
sı
́
(11) Idec, A.; Pawlicki, M.; Latos-Grazynski, L. Three-Stage
̇
Aromaticity Switching in Boron(III) and Phosphorus(V) N-Fused p
-Benziporphyrin. Chem.Eur. J. 2019, 25, 200−204.
́ ́
(12) Step̧ ien, M.; Szyszko, B.; Latos-Grazynski, L. Steric Control in
the Synthesis of P-Benziporphyrins. Formation of a Doubly n-
Confused Benzihexaphyrin Macrocycle. Org. Lett. 2009, 11, 3930−
3933.
HR-MS, 1H, 13C{1H}, 2D NMR, absorption and
electrochemical data, and DFT studies (PDF)
́
́
̇
nski, L.; Sprutta, N.; Chwalisz, P.;
(13) Stępien, M.; Latos-Grazy
Szterenberg, L. Expanded Porphyrin with a Split Personality: A
AUTHOR INFORMATION
Corresponding Author
Mangalampalli Ravikanth − Indian Institute of Technology,
Mumbai 400076, India; orcid.org/0000-0003-0193-
6081; Phone: 91-22-5767176; Email: ravikanth@
chem.iitb.ac.in; Fax: 91-22-5723480
■
Hu
8019.
(14) Szyszko, B.; Sprutta, N.; Chwalisz, P.; Stępien, M.; Latos-
̈
ckel−Mobius Aromaticity Switch. Angew. Chem. 2007, 119, 8015−
̈
́
́
Grazynski, L. Huckel and Mobius Expandedpara-Benziporphyrins:
̇ ̈
̈
Synthesis and Aromaticity Switching. Chem.Eur. J. 2014, 20, 1985−
1997.
Authors
̈
(15) Yoon, Z. S.; Osuka, A.; Kim, D. Mobius aromaticity and
antiaromaticity in expanded porphyrins. Nat. Chem. 2009, 1, 113−
Nisha Rawat − Indian Institute of Technology, Mumbai
400076, India
Avisikta Sinha − Indian Institute of Technology, Mumbai
400076, India
Dijo Prasannan − Indian Institute of Technology, Mumbai
400076, India
122.
(16) Kumar, S.; Ravikanth, M. Synthesis of Stable [28π] m-
Benzihexaphyrins (1.0.0.1.1.1). J. Org. Chem. 2017, 82, 12359−12365.
(17) Sreedhar Reddy, J.; Anand, V. G. π-Conjugated macrocycles
from thiophenes and benzenes. Chem. Commun. 2008, 1326−1328.
(18) Jeong, S.-D.; Park, K. J.; Kim, H.-J.; Lee, C.-H. Meso-
Alkylidenyl-Thia(p-Benzi)Porphyrins and Their Unusual Protonation
Selectivity. Chem. Commun. 2009, 5877−5879.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00439
(19) Sengupta, R.; Thorat, K. G.; Ravikanth, M. Effects of Core
Modification on Electronic Properties of Para-Benziporphyrins. Inorg.
Chem. 2019, 58, 12069−12082.
Notes
The authors declare no competing financial interest.
(20) Sengupta, R.; Thorat, K. G.; Ravikanth, M. Synthesis of
Nonaromatic and Aromatic Dithia Benzisapphyrins. J. Org. Chem.
2018, 83, 11794−11803.
ACKNOWLEDGMENTS
■
M.R. acknowledges the financial support from Science &
Engineering Research Board (SERB), Govt. of India. N.R.
thanks University Grants Commission, Govt. of India; A.S. and
D.P. thanks IIT Bombay for the Institute Fellowship.
(21) Lash, T. D.; Chaney, S. T. Oxypyriporphyrin, the First Fully
Aromatic Porphyrinoid Macrocycle with a Pyridine Subunit. Chem.
Eur. J. 1996, 2, 994−998.
́
́
(22) (a) Mysliborski, R.; Latos-Grazynski, L. Carbaporphyrinoids
Containing a Pyridine Moiety: 3-Aza-Meta-Benziporphyrin and 24-
Thia-3-Aza-Meta-Benziporphyrin. Eur. J. Org. Chem. 2005, 5039−
5048. (b) Lash, T. D.; Pokharel, K.; Yant, V. R.; Ferrence, G. M.;
Ferrence, G. M. Aromatic and Nonaromatic Pyriporphyrins†. Org.
Lett. 2007, 9, 2863−2866.
REFERENCES
■
(1) Lash, T. D. Recent Advances on the Synthesis and Chemistry of
Carbaporphyrins and Related Porphyrinoid Systems. Eur. J. Org.
Chem. 2007, 5461−5481.
6672
https://doi.org/10.1021/acs.joc.1c00439
J. Org. Chem. 2021, 86, 6665−6673

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(23) Das, M.; Chitranshi, S.; Murugavel, M.; Adinarayana, B.;
Suresh, C. H.; Srinivasan, A. Isosmaragdyrin with an N3C2 core:
stabilization of Rh(i) and organo-Pt(ii) complexes. Chem. Commun.
2020, 56, 3551−3554.
(24) Setsune, J.-i.; Toda, M.; Yoshida, T.; Imamura, K.; Watanabe,
K. The Synthesis and Dynamic Structures of Multinuclear Complexes
of Large Porphyrinoids Expanded by Phenylene and Thienylene
Spacers. Chem.Eur. J. 2015, 21, 12715−12727.
(25) Hong, S.-J.; Dutta, R.; Kumar, R.; He, Q.; Lynch, V. M.; Sessler,
J. L.; Lee, C.-H. meso-Alkylidenyl dibenzihexaphyrins: synthesis and
protonation studies. Chem. Commun. 2019, 55, 9693−9696.
(26) Rawat, N.; Thorat, K. G.; Kumar, S.; Ravikanth, M. Synthesis of
Expanded Hetero 2,6-Pyrihexaphyrins. Eur. J. Org. Chem. 2020, 736−
743.
(27) Das, B.; McPherson, J. N.; Colbran, S. B. Oligomers and
macrocycles with [m]pyridine[n]pyrrole (m + n ≥ 3) domains:
Formation and applications of anion, guest molecule and metal ion
complexes. Coord. Chem. Rev. 2018, 363, 29−56.
(28) Mori, D.; Yoneda, T.; Suzuki, M.; Hoshino, T.; Neya, S. meso
-Diketopyripentaphyrin and Diketopyrihexaphyrin as Macrocyclic
Tripyrrinone Ligands for Ni II Ions. Chem.Asian J. 2019, 14,
4169−4173.
(29) Sim, E.-K.; Jeong, S.-D.; Yoon, D.-W.; Hong, S.-J.; Kang, Y.;
Lee, C.-H. Porphyrins Bearing Stablemeso-Alkylidenyl Double Bonds.
A New Family of Nonplanar Porphyrinoids. Org. Lett. 2006, 8, 3355−
3358.
(30) Neya, S.; Suzuki, M.; Mochizuki, T.; Hoshino, T.; Kawaguchi,
A. T. Porphyrinoid Aromaticity Induced by the Interaction between
Oxidized and Reduced Pyridine Subunits. Eur. J. Org. Chem. 2015,
3824−3829.
(31) Setsune, J.-I.; Watanabe, K. Cryptand-like Porphyrinoid
Assembled with Three Dipyrrylpyridine Chains: Synthesis, Structure,
and Homotropic Positive Allosteric Binding of Carboxylic Acids. J.
Am. Chem. Soc. 2008, 130, 2404−2405.
(32) Stanger, A. Nucleus-Independent Chemical Shifts (NICS):
Distance Dependence and Revised Criteria for Aromaticity and
Antiaromaticity. J. Org. Chem. 2006, 71, 883−893.
(33) Chen, Z.; Wannere, C. S.; Corminboeuf, C.; Puchta, R.;
Schleyer, P. v. R. Nucleus-Independent Chemical Shifts (NICS) as an
Aromaticity Criterion. Chem. Rev. 2005, 105, 3842−3888.
(34) Krygowski, T. M.; Szatylowicz, H.; Stasyuk, O. A.;
Dominikowska, J.; Palusiak, M. Aromaticity from the Viewpoint of
Molecular Geometry: Application to Planar Systems. Chem. Rev.
2014, 114, 6383−6422.
(35) Peeks, M. D.; Gong, J. Q.; McLoughlin, K.; Kobatake, T.;
Haver, R.; Herz, L. M.; Anderson, H. L. Aromaticity and
Antiaromaticity in the Excited States of Porphyrin Nanorings. J.
Phys. Chem. Lett. 2019, 10, 2017−2022.
(36) Mills, N. S.; Llagostera, K. B. Summation of Nucleus
Independent Chemical Shifts as a Measure of Aromaticity. J. Org.
Chem. 2007, 72, 9163−9169.
(37) Schleyer, P. V. R.; Maerker, C.; Dransfeld, A.; Jiao, H.; Van
Eikema Hommes, N. J. R. Nucleus-Independent Chemical Shifts: A
Simple and Efficient Aromaticity Probe. J. Am. Chem. Soc. 1996, 118,
6317−6318.
(38) Lu, X.; Gopalakrishna, T. Y.; Phan, H.; Herng, T. S.; Jiang, Q.;
Liu, C.; Li, G.; Ding, J.; Wu, J. Global Aromaticity in Macrocyclic
Cyclopenta-Fused Tetraphenanthrenylene Tetraradicaloid and Its
Charged Species. Angew. Chem. 2018, 130, 13236−13240.
(39) Fliegl, H.; Sundholm, D.; Taubert, S.; Pichierri, F. Aromatic
Pathways in Twisted Hexaphyrins. J. Phys. Chem. A 2010, 114, 7153−
7161.
(40) Huang, W.; Sergeeva, A. P.; Zhai, H.-J.; Averkiev, B. B.; Wang,
L.-S.; Boldyrev, A. I. A concentric planar doubly π-aromatic B19−
cluster. Nat. Chem. 2010, 2, 202−206.
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https://doi.org/10.1021/acs.joc.1c00439
J. Org. Chem. 2021, 86, 6665−6673