Synthesis of Unsymmetrical Heterobenzisapphyrins

Article abstract of DOI:10.1021/acs.joc.8b02616

Two examples of highly unsymmetrical heterobenzisapphyrins containing one benzene, two pyrroles, one furan, and one thiophene ring connected via four meso-carbons and one direct bond were prepared over a sequence of five steps in 8-9% yields. The X-ray st

Full text of DOI:10.1021/acs.joc.8b02616

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Synthesis of Unsymmetrical Heterobenzisapphyrins
Sunit Kumar, Kishor Gulab Thorat, and Mangalampalli Ravikanth
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02616 • Publication Date (Web): 30 Nov 2018
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Synthesis of Unsymmetrical Heterobenzisapphyrins
Sunit Kumar, Kishor G. Thorat and Mangalampalli Ravikanth*
Indian Institute of Technology, Powai, Mumbai, 400076, India
Fax: 91-22-5723480; Tel: 91-22-5767176
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ABSTRACT: Two examples of highly unsymmetrical heterobenzisapphyrins containing one benzene, two pyrroles, one furan and
one thiophene rings connected via four meso carbons and one direct bond were prepared over a sequence of five steps in 8-9% yields.
The X-ray structure revealed that the furan ring was inverted from the macrocyclic framework and the macrocycle was nearly planar.
Spectral and electrochemical studies indicated that the macrocycle was nonaromatic in nature due to lack of conjugation.
Sapphyrins are 22π electron aromatic macrocycles
containing five pyrrole rings connected via four meso-carbons
and one direct pyrrole-pyrrole link. Sapphyrins were
serendipitously discovered by R. B. Woodward and co-workers
during their early investigations into the total synthesis of
Vitamin B12.1 Although some initial synthetic reports were
available on sapphyrins, these pentapyrrolic macrocycles have
received tremendous attention only after their accidental
discovery as good receptors for anions by Sessler and co-
workers.2 Thus, Sessler and co-workers in early 1990’s revived
the interest on sapphyrin macrocycles and showed their potential
applications in viral photoeradication,3 as photosensitizers in
photodynamic therapy,4 in anion binding/sensing,5 ligand for
metal coordination and in material science.6 Over the years, new
analogues of sapphyrins such as heterosapphyrins resulted from
the replacement of one or more pyrrole rings with thiophene,
furan, selenophene; N- or X-confused heterosapphyrins in which
pyrrole or heterocycle is inverted were synthesized and their
properties were studied.7 Carbasapphyrins in which one or two
pyrrole rings are replaced by carbacycles;8 polycyclic aromatic
moieties embedded sapphyrins such as biphenyl sapphyrins and
phenanthrene sapphyrins9 and so on were prepared and explored
their properties and applications in various fields.8 Interestingly,
among carbasapphyrins, the reports on phenylene containing
sapphyrins are very rare though significant amount of work has
been done on benzene containing porphyrins.10 The benzene
containing porphyrin analogues have been used to understand
aromaticity and conjugation since the characteristics of these
macrocycles vary from nonaromatic to highly aromatic and few
examples of antiaromatic structures are also known.11 The
benzene containing porphyrinoids readily forms organometallic
derivatives and can be used as chemical sensors and also in
molecular recognition studies.12 To date there are only limited
heterosapphyrins are required to understand their physico-
chemical and coordination properties. In this paper, we report
two examples of highly unsymmetrical heterobenzisapphyrins
1a and 1b containing one benzene, one thiophene, one furan and
two pyrroles connected via four meso-carbons and one direct
benzene-thiophene link which involves multistep synthesis as
depicted in Scheme 1. The single crystal structure analysis of
one of the heterobenzisapphyrins 1b revealed that the furan ring
was inverted from the macrocyclic framework and the spectral
and electrochemical studies supported the nonaromatic nature of
the heterobenzisapphyrins 1a and 1b.
The unsymmetrical heterobenzisapphyrins 1a and 1b were
synthesized as shown in Scheme 1. m-Bromobenzaldehyde was
reacted with thiophene 2-boronic acid under Suzuki coupling
reaction conditions (Experimental Section), followed by silica
gel column chromatographic purification afforded m-
thienylbenzaldehyde 2 as a yellow oily liquid in 78% yield. The
compound 2 was subjected to Grignard reaction by treating it
with ArMgBr in THF followed by column chromatographic
purification to afford the corresponding mono-carbinol 3a/3b as
a white solid in 50-53% yields. The appropriate mono-carbinol
3a/3b was treated first with 1.2 equivalents of n-BuLi followed
by the addition of 1.2 equivalents of 4-methyl benzaldehyde in
dry THF at 0° C. After workup, the crude compound was
subjected to silica gel column chromatographic purification and
afforded the respective dicarbinols 4a/4b as pale white solids in
45-53% yields. The dicarbinols 4a/4b were treated with excess
pyrrole in 1,2-dichloroethane in the presence of catalytic amount
.
of BF3 OEt2 and the resulting crude compounds were purified by
silica gel column chromatography to afford the respective pure
tetrapyranes 5a/5b as pale yellow oily pastes in 56-63% yields
(Scheme 1).
reports
available
on benzene containing expanded
porphyrinoids. However, more examples on benzene containing
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Scheme 1: Synthesis of Heterobenzisapphyrins (1a/1b).
(Scheme 1). The crude reaction mixtures were subjected to
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alumina column chromatography and the major brown band was
collected to afford the desired heterobenzisapphyrins 1a/ 1b as
brown solids in 8-9% yields. Attempts to condense the 5a/5b
with other thiophene/selenophene diols to obtain the
corresponding unsymmetrical heterobenzisapphyrins were
unsuccessful.
The heterobenzisapphyrins 1a/ 1b were
characterized by HR-MS, 1D/2D NMR spectroscopy and X-ray
crystallography. The respective molecular ion peak in HR-MS
confirmed the identities of heterobenzisapphyrins 1a and 1b.
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1
1
The H and H-1H COSY NMR spectra of macrocycle 1a are
shown in Figure 1. The macrocycle showed more number of
resonances due to its asymmetric nature and the X-ray structure
also showed that the furan ring was inverted from the
macrocyclic framework (Figure 2). Thus, we identified and
assigned all resonances based on location, integration, coupling
constant and cross peak correlations in COSY and NOESY
1
spectra. In the H NMR spectrum of macrocycle 1a, the anisyl -
OCH3 protons (type I) appeared as a singlet resonance at 3.91
ppm showed NOE correlation with a doublet at 7.20 ppm which
we identified as type l protons of meso-anisyl group. The
multiplet in the region of 7.35-7.38 ppm was assigned to type m
protons of meso-anisyl group based on its cross peak correlation
with type l protons. The inner -CH proton of the o-phenylene unit
was observed as broad singlet at 8.16 ppm. The doublet at 7.85
ppm was assigned to type b proton of m-phenylene unit based on
its NOE correlation with type m proton. The type b proton
showed cross peak correlation with type c proton of m-phenylene
unit which appeared along with type m protons as a multiplet in
the region of 7.35-7.38 ppm. The type d proton of m-phenylene
was also identified based on its cross peak correlation with type c
proton and it appeared as a multiplet in the region of 7.14-7.16
ppm. The type II -CH3 protons of meso-tolyl group appeared as a
singlet at 2.49 ppm and showed NOE correlation with a doublet
at 7.31 ppm (type n) which in turn showed cross peak correlation
with type o protons which appeared as a multiplet in the region
of 7.48-7.52 ppm. The type f proton of thiophene which appeared
as a doublet at 7.07 ppm was identified based on NOE
correlation with type o protons. The type e proton appeared as
multiplet in the region of 7.48-7.52 ppm along with type o
protons which was identified since it showed cross peak
correlation with type f protons. The two doublets at 6.91 ppm and
6.97 ppm were identified as type g and type h protons of pyrrole
I ring based on their cross peak correlations. The pyrrole II ring
J protons appeared as a doublet at 6.88 ppm whereas the type k
protons appeared as a multiplet along with type d protons. The
inverted furan ring type i and type i’ protons appeared as two sets
of doublets at 7.24 and 7.41 ppm, respectively were also
identified based on similar correlations in 2D NMR spectra. The
other meso-tolyl protons were also similarly identified and
assigned. Similarly, all the resonances in compound 1b were
also identified and assigned using 1D and 2D NMR
spectroscopy. Thus, although the benzisapphyrin macrocycles 1a
and 1b were asymmetric, 1D and 2D NMR spectroscopy was
very useful in deducing the molecular structure of macrocycles.
Figure 1: 1D and 2D NMR spectra for compound 1a recorded in
CDCl3 at room temperature.
The
other
required
intermediate,
2,5-bis(p-
tolyl)hydroxymethylfuran 6, was prepared by using reported
method.13 The unsymmetrical heterobenzisapphyrins 1a/1b were
synthesized by 1:1 condensation of appropriate tetrapyrrane
(5a/5b)and furan dicarbinol 6 in CH2Cl2 in the presence of
catalytic amount of TFA at room temperature for 1 h under an
inert atmosphere followed by oxidation with 2,3-dichloro-1,4-
benzoquinone (DDQ) in open air for an additional 30 min.
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We
obtained
the
molecular
structure
of
and
2×10-2 M), change in the color of the solution was noticed from
green to yellow and the absorption bands experienced
bathochromic shifts (456 to 486 and 683 to 948 nm) with clear
isosbestic points (360, 423, 466 and 770 nm) as shown in Figure
3. Compound 1b and its dicationic species 1b.2H2+ also showed
similar absorption features (Figure S31). The systematic
heterobenzisapphyrin 1b as shown in Figure
crystallographic data are given in Tables S1 & S2. Suitable
single crystals of compound 1b was obtained by slow
evaporation of chloroform/pet-ether solution
2
at room
temperature over a period of one week and the macrocycle
crystallizes in a orthorhombic system with a Fdd2 space group.
The crystal structure revealed that the macrocycle core hetero
atoms and benzene inner carbon atom (N1, N2, S1, O1 and C6)
were almost in the plane whereas the two pyrrole rings, furan,
thiophene and benzene rings were deviated alternately in upward
and downward directions with dihedral angles of 6.87°, 15.57°,
30.92°, 11.65° and 14.80° with respect to the mean plane (C11-
C16-C21-C26). The furan ring was found inverted from
macrocyclic framework to get relief from electrostatic repulsions
between electron lone pairs on N1, N2 and O1. The phenylene
moiety in macrocycle 1b retained its benzene like features as
seen from analysis of C-C bond lengths within the ring
(1.360(16) to 1.411(14) Å) except C4-C5 bond (1.429(15) Å)
possessing single bond characteristic features indicates absence
of conjugation. However, remaining C-C, C-S, C-O and C-N
bond lengths in the rest of the macrocyclic core other than the m-
phenylene ring displays typical conjugated bond behavior within
the macrocycle. All the meso substituents in 1b were arranged in
orthogonal fashion with respect to the palne of the macrocycle. .
Overall, the crystal structure analysis revealed that the
heterobenzisapphyrin 1b adopts almost planar geometry with
inversion of furan ring towards macrocyclic framework and also
supported nonaromatic character due to lack of conjugation.
1
protonation studies was also followed by H NMR spectroscopy
which showed the upfield shifts of all benzene, pyrrole, furan,
and thiophene protons along with appearance of two inner -NH
protons at 8.96 and 11.34 ppm due to formation of 1a.2H2+
(Figure S32 and S33). The redox properties of 1a/1b were
investigated by cyclic voltammetry and differential pulse
voltammetry in CH2Cl2 containing TBAP (0.1 M) as supporting
electrolyte. The cyclic voltamograms along with differential
pulse voltamograms of 1a and 1b are shown in Figure 4.
Macrocycles 1a and 1b exhibit three irreversible oxidations, one
reversible reduction and one irreversible reduction. For example,
the heterobenzisapphyrin macrocycle 1a showed three
irreversible oxidations at 0.89, 1.15 and 1.41 V; one reversible
reduction at -0.68 V and one irreversible reduction at -1.53 V.
The ease of reduction of macrocycles 1a/1b supports the electron
deficient nature of heterobenzisapphyrins. Also, these
macrocycle were found to be difficult to oxidize compared to
hetero- m-benzisapphyrins reported by our group.10b
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Figure 3: Change in the absorption spectra of 1a (2×10-5 M)
upon the systematic addition of (2×10-2 M) trifluoroacetic acid in
CHCl3 at room temperature.
Figure 2: X-ray structure of heterobenzisapphyrin 1b with 50%
thermal ellipsoid probability (a) front view and (b) side view. All
the meso-aryl groups and hydrogen atoms are omitted for clarity.
Further, the density functional theory (DFT) calculations were
carried out for 1b and its di-protonated form 1b.2H2+ to
understand the changes in structural, spectral and
electrochemical properties of 1b before and after protonation.
The S0 (ground) state optimized geometries are presented in
We
have
studied
the
absorption
properties
of
heterobenzisapphyrins 1a/1b and their diprotonated forms
1a.2H2+/1b.2H2+ which were generated by addition of excess
amounts of TFA (Figure S31). The absorption spectra of 1a upon
systematic addition of TFA to generate its protonated derivative
1a.2H2+ is shown in Figure 3. The absorption spectrum of 1a
showed one broad absorption band at 683 nm and two relatively
sharp bands at 456 nm and 393 nm. The unsymmetrical
heterobenzisapphyrins 1a and 1b were found to show blue
shifted absorption maxima compared to our recently reported
hetero- m-benzisapphyrins.10b Upon protonation of 1a (2×10-5 M)
by systematically increasing the addition of TFA (0-3.0 equiv.
Figure S35. The DFT study showed very similar structure for 1b
as obtained by X-ray and predicted more distorted structure for
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Computational details: DFT calculations for the compound 1b
-1.53
-1.53
and its diprotonated form 1b.2H2+ in unrestricted mode were
-0.66
-0.68
performed using Gaussian 09 program package15 as described
previously.14
1.47
0.92
0.89
1.20
1b
1a
3-(Thiophen-2-yl)benzaldehyde (2): Thiophene-2-boronic acid
(5.19 g, 40.54 mol) was added to the solution of 3-
bromobenzaldehyde (5.00 g, 27.02 mmol) and Pd(PPh3)4 (312
mg, 2.70 mmol) in 50 mL 1,2-dimethoxyethane under nitrogen
atmosphere at room temperature. Subsequently, aqueous solution
of sodium carbonate (20 mL, 2 M) was added to the reaction.
The resulting mixture was heated at reflux for 12 h, with
vigorous stirring under nitrogen atmosphere. Then the reaction
mixture was allowed to cool to room temperature and poured
into water, and extracted with diethyl ether. The combined
organic layers were washed with water, brine and dried over
sodium sulfate. The crude product obtained after removal of
solvent was subjected to silica gel column chromatography using
a petroleum ether/ethyl acetate (95:5) solvent mixture afforded
3-(thiophen-2-yl)benzaldehyde 2 as pale yellow oily liquid (4.10
g, 78% yield). 1H NMR (400 MHz, CDCl3): 7.10 (dd, J = 3.6 Hz,
1H), 7.35 (dd, J = 3.6 Hz, 1H), 7.40 (dd, J = 3.6 Hz, 1H), 7.55 (t,
J = 7.6 Hz, 1H), 7.77-7.80 (m, 1H), 7.85-7.88 (m, 1H), 8.10 (t, J
= 1.6 Hz, 1H), 10.06 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3):
δ = 124.2, 125.9, 126.8, 128.4, 128.8, 129.8, 131.7, 135.6, 137.1,
142.8, 192.2 ppm; HRMS (ESI-TOF) m/z: [M-H]+ calcd for
C11H7OS 187.0212, found 187.0203.
1.41
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1.15
1.5
1.0
0.5
0.0
-0.5 -1.0 -1.5
E/V vs SCE
Figure 4: Comparison of cyclic voltamograms of compound 1a
(black line) and compound 1b (red line) and the differential pulse
voltammogram (dotted blue line) recorded in CH2Cl2 with 0.1 M
TBAP as the supporting electrolyte at a scan rate of 50 mVs-1.
its di-protonated form 1b.2H2+. The optimized geometry of the
compound 1b.2H2+ indicated that the heterocyclic rings were
deviated more from the plane of macrocycle compared to its non-
protonated form 1b. Analysis of selected frontier molecular
orbitals (FMOs) of the compounds 1b and 1b.2H2+ suggested
that the HOMOs in both were localized mainly on furan ring and
meso substituents adjacent to the furan ring (Figure S36). The
LUMOs were distributed essentially all over the macrocyclic
core leaving no orbital densities on meso substituents. In
1b.2H2+, the FMOs were stabilized to greater extent and there
was decrease in band gap suggesting formation of electron
deficient species and supports the bathochromic shift in
absorption upon protonation of 1b.
(4-Methoxyphenyl)(3-(thiophen-2-yl)phenyl)methanol 3a: 3-
(thiophen-2-yl)benzaldehyde 2 (2.00 g, 10.62 mmol) was
dissolved in dry degassed THF (100 mL) and the freshly
prepared PhMgBr (17.1 mL of a 3M solution in Et2O, 53.12
mmol) was added to the reaction mixture and the resulting
mixture was stirred for 8 h at room temperature. The reaction
mixture was slowly quenched with NH4Cl and extracted with
diethyl ether. The extracts were washed twice with water, dried
over sodium sulfate and the solvent was removed under reduced
pressure. The crude compound was purified by silica gel column
chromatography using petroleum ether/ethyl acetate (85:15). The
evaporation of solvent on rotary evaporator under reduced
pressure gave the desired compound (4-methoxyphenyl)(3-
(thiophen-2-yl)phenyl)methanol 3a as white solid (1.60 g, 50 %
In conclusion, we have synthesized two examples of new
highly unsymmetrical heterobenzisapphyrins over a sequence of
steps. The heterobenzisapphyrins reported here are quite
different in structure and properties compared to some known
heterobenzisapphyrins.10 The crystal structure revealed that the
heterobenzisapphyrin adopts almost planar conformation with
inversion of furan ring from the macrocyclic framework. The
NMR and absorption studies support the asymmetric and
nonaromatic nature of the macrocycles. The redox studies
indicated the macrocycles were electron-deficient.
1
yield). mp: 105-107 °C; H NMR (400 MHz, CDCl3): 2.16 (d, J
= 3.2 Hz, 1H), 3.72 (s, 3H), 5.76 (d, J = 2.4 Hz, 1H), 6.15 (d, J =
8.4 Hz, 2H), 6.99 (dd, J = 3.6 Hz, 1H), 7.18-7.28 (m, 6H), 7.42-
7.44 (m, 1H), 7.58 (bs, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ
= 29.8, 55.4, 75.8, 114.1, 123.4, 124.0, 125.0, 125.2, 125.7,
128.1, 128.2, 129.1, 134.7, 136.1, 144.4, 144.8, 159.3 ppm;
HRMS (ESI-TOF) m/z: [M-OH]+ calcd for C18H15OS 279.0838,
found 279.0834.
Experimental Section
General Experimental. 3-bromobenzaldehyde, thiophene,
pyrrole, trimethylborate, BF3·OEt2, trifluoroacetic acid (TFA)
and 2, 3-dichloro-5, 6-dicyano-1,4-benzoquinone (DDQ) were
used as obtained from Sigma-Aldrich. All other chemicals used
for the synthesis were reagent grade unless otherwise specified..
The spectral, electrochemical and X ray single crystal structure
analyses were performed as previously described.14 For UV-vis,
the solution for all compounds (2×10-5 M) were prepared by
using spectroscopic grade CHCl3 solvent.The X-ray data for
compound 1b (CCDC 1871885) can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Phenyl(3-(thiophen-2-yl)phenyl)methanol (3b): Phenyl(3-
(thiophen-2-yl)phenyl)methanol 3b was prepared by following
the same procedure as given for compound 3a by using 3-
(thiophen-2-yl)benzaldehyde 2 (2.00 g, 0.472 mmol) and
PhMgBr (17.1 mL of a 3M solution in Et2O, 53.12 mmol). The
crude compound was purified by silica gel column
chromatography and obtained the desired compound 3b using
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petroleum ether/ ethyl acetate (90:10) as white solid (1.50 g, 53
% yield). mp: 100-102 °C; H NMR (500 MHz, CDCl3): 2.25
tolyl)methanol 4a (1.00 g, 2.40 mmol) and pyrrole (1.61 g, 24.01
mmol) in 1,2-dichloroethane (150 mL) under nitrogen, after 15
min. BF3·OEt2 (68.15 mg, 0.48 mmol) was added and the
resulting mixture was stirred under reflux for 6 h. The solution
was cooled to room temperature and the solvent was evaporated
on a rotatory evaporator. The product was purified by silica gel
column chromatography by eluting with a mixture of pet
ether/ethyl acetate in a ratio of 85:15. Evaporation of the product
fractions gave the benzitetrapyrrane 5a as a pale-colored oil
1
(bs, 1H), 5.88 (s, 1H), 7.06 (dd, J = 3.6 Hz, 1H), 7.26-7.31 (m,
4H), 7.33-7.36 (t, 3H), 7.40-7.42 (m, 2H), 7.51-7.52 (m, 1H),
7.66 (t, J = 1.7 Hz, 1H); 13C{1H} NMR (125 MHz, CDCl3): δ =
76.3, 123.4, 124.2, 125.1, 125.4, 125.8, 126.7, 128.1, 128.7,
129.2, 134.8, 143.8, 143.7, 144.4, 144.6 ppm; HRMS (ESI-TOF)
m/z: [M-OH]+ calcd for C17H13S 249.0732, found 249.0732.
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(5-(3-(Hydroxy(4-methoxyphenyl)methyl)phenyl)thiophen-2-
yl)(p-tolyl)methanol 4a: A sample of benzene thia mono-ol 3a
(1 g, 3.37 mmol) in 30 mL of diethyl ether in a three neck round
bottom flask under N2 atmosphere was cooled to -10 °C.
Tetramethylethylenediamine (TMEDA) (0.98 g, 1.26 mL, 8.43
mmol) and n-butyl lithium (5.27 mL, 1.6 M solution in hexane)
were added to the stirred solution. The resulting mixture was
vigorously stirred at 0° C for 1.5 h. Then, to the reaction mixture,
an ice cold solution of p-tolulaldehyde (0.80 mL, 6.74 mmol) in
dry THF (40mL) was added and stirring was continued for an
additional 15 min at 0 ºC. The reaction was quenched by adding
an ice-cold NH4Cl solution (50 mL, ca. 1 M). The organic layer
was diluted with diethyl ether and washed 2-3 times with water,
brine and dried over anhydrous sodium sulfate. The crude
compound obtained after removal of solvent was subjected to
silica gel column chromatography using petroleum ether/ethyl
acetate (70:30) afforded 4a as a white solid (0.75 g, 53 % yield).
mp: 114-116 °C; 1H NMR (500 MHz, CDCl3): 2.27 (bs, 1H),
2.38 (s, 3H), 2.48 (bs, 1H), 3.81 (s, 3H), 5.82 (s, 1H), 6.01 (s,
1H), 6.85-6.89 (m, 3H), 7.15 (d, J = 3.6 Hz, 1H), 7.20 (d, J = 7.9
Hz, 2H), 7.25-7.34 (m, 4H), 7.37 (d, J = 7.9 Hz, 2H), 7.46-7.47
(m, 1H), 7.60 (bs, 1H); 13C{1H} NMR (125 MHz, CDCl3): δ =
21.2, 21.3, 55.4, 60.5, 72.6, 114.1, 122.9, 123.7, 124.9, 125.6,
125.8, 126.4, 128.1, 129.1, 129.4, 134.6, 136.0, 138.0, 140.2,
144.3, 144.8, 147.9, 153.3 ppm; HRMS (ESI-TOF) m/z: [M-
OH]+ calcd for C26H23O2S 399.1413, found 399.1414.
1
(0.70 g, 56% yield) that was stored in the freezer. H NMR (500
MHz, CDCl3): 2.37 (s, 3H), 3.81 (s, 3H), 5.43 (s, 1H), 5.62 (s,
1H), 5.83 (bs, 1H), 6.00 (bs, 1H), 6.17-6.20 (m, 2H), 6.72 (bs,
2H), 6.73 (d, J = 3.5 Hz, 1H), 6.88 (d, J = 8.5 Hz, 2H), 7.06-7.21
(m, 8H), 7.27-7.30 (m, 1H), 7.40-7.43 (m, 2H), 7.83 (bs, 1H),
7.95 (bs, 1H); 13C{1H} NMR (125 MHz, CDCl3): δ = 21.2, 45.8,
49.8, 55.4, 107.6, 108.0, 108.4, 108.5, 113.0, 114.0, 117.3, 117.4,
122.8, 124.0, 126.1, 126.8, 127.8, 128.4, 129.1, 129.5, 129.9,
131.4, 133.2, 133.8, 134.7, 135.0, 136.9, 139.7, 143.3, 144.1,
146.9, 158.5 ppm; HRMS (ESI-TOF) m/z: [M+K]+ calcd for
C34H30N2OSK 553.1710, found 553.1715.
2-((3-(5-((1H-Pyrrol-2-yl)(p-tolyl)methyl)thiophen-2-
yl)phenyl)(phenyl)methyl)-1H-pyrrole
(5b);
The
benzitetrapyrrane 5b was prepared by following the same
procedure as given for compound 5a by using (3-(5-(hydroxy(p-
tolyl)methyl)thiophen-2-yl)phenyl)(phenyl)methanol 4b (1.00 g,
2.59 mmol), pyrrole (1.74 g, 25.87 mmol), and BF3·OEt2 (73.44
mg, 0.51 mmol). The crude compound was purified by alumina
column chromatography and obtained the desired compound 5b
using petroleum ether/ ethyl acetate (90:10) as pale-colored oil
1
(0.80 g, 63% yield). H NMR (400 MHz, CDCl3): 2.34 (s, 3H),
5.45 (s, 1H), 5.60 (s, 1H), 5.81 (bs, 1H), 5.97 (bs, 1H), 6.14-
6.16 (m, 2H), 6.71 (bs, 2H), 6.73 (dd, J = 3.6 Hz, 1H), 7.03-7.05
(m, 1H), 7.08 (d, J = 3.6 Hz, 1H), 7.12-7.25 (m, 8H), 7.28-7.32
(m, 3H), 7.38-7.41(m, 2H), 7.81 (bs, 1H), 7.92 (bs, 1H); 13C{1H}
NMR (100 MHz, CDCl3): δ = 21.2, 45.6, 50.55, 107.5, 108.0,
108.3, 108.4, 117.2, 122.6, 124.0, 126.0, 126.7, 127.7, 128.2,
128.5, 128.8, 129.0, 129.3, 133.0, 133.2, 134.6, 136.8, 139.6,
142.7, 143.2, 143.6, 146.8 ppm; HRMS (ESI-TOF) m/z: [M+H]+
calcd for C33H29N2S 485.2046, found 485.2051.
(3-(5-(Hydroxy(p-tolyl)methyl)thiophen-2-
yl)phenyl)(phenyl)methanol 4b: Compound 4b was prepared
by following the same procedure as given for compound 4a by
using phenyl(3-(thiophen-2-yl)phenyl)methanol 3b (1.00 g, 3.35
mmol), tetramethylethylenediamine (TMEDA) (1.09 g, 1.40 mL,
9.38 mmol), n-butyl lithium (5.86 mL of 1.6 M solution in
hexane) and p-tolualdehyde (0.90 mL 7.5 mmol). The crude
compound was purified by silica gel column chromatography
and obtained the desired compound 4b using petroleum ether/
ethyl acetate (75:25) as a white solid (0.80 g, 45% yield). mp:
Compound 1a: A sample of benzitetrapyrrane 5a (100 mg, 0.19
mmol) and furan-2,5-diylbis(p-tolylmethanol) 6 (64 mg, 0.19
mmol) were dissolved in 70 mL of CH2Cl2 under nitrogen
atmosphere. Then to this was added 10 µL of TFA (0.02 mmol)
and the reaction mixture was allowed to stir at room temperature
for 1 h. After 1h, DDQ (107 mg, 0.24 mmol) was added and the
reaction mixture was stirred in open air for additional 30 min.
The solvent was removed under reduced pressure and the crude
compound was purified by basic alumina column
chromatography using petroleum ether/ ethyl acetate (85:15)
afforded 1a as a dark green colored solid (12 mg, 8 % yield). mp:
1
110-112 °C H NMR (400 MHz, CDCl3): 2.29 (bs, 1H), 2.36 (s,
3H), 2.42 (bs, 1H), 5.84 (s, 1H), 5.99 (s, 1H), 6.83 (dd, J = 3.7
Hz, 1H), 7.12 (d, J = 3.7 Hz, 1H), 7.18 (d, J = 7.8 Hz, 2H), 7.23-
7.39 (m, 9H), 7.43-7.46 (m, 1H), 7.60 (t, J = 1.6 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3): δ = 21.3, 72.6, 76.3, 122.9,
123.9, 125.0, 125.8, 125.9, 126.4, 127.8, 129.1, 129.4, 134.7,
138.0, 140.2, 143.7, 144.2, 144.6, 148.0 ppm; HRMS (ESI-TOF)
m/z: [M-OH]+ calcd for C25H21OS 369.1308, found 369.1308.
1
decomposes at ∼120 °C; H NMR (500 MHz, CDCl3): δ = 2.38
(s, 3H, -CH3), 2.40 (s, 3H, -CH3), 2.49 (s, 3H, -CH3), 3.91 (s, 3H,
-OCH3), 6.88 (d, J = 4.5 Hz, 2H, β-Py), 6.91 (d, J = 4.0 Hz, 2H,
β-Py), 6.97 (d, J = 4.0 Hz, 2H, β-Py), 7.07 (d, J = 8.7 Hz, 2H,
Ar), 7.07 (d, J = 5.4 Hz, 2H, β-Th), 7.14-7.16 (m, 3H, β-Py and
Phenylene), 7.18-7.22 (m, 5H, β-Oxa, Ar), 7.31 (d, J = 8.7 Hz,
2-((3-(5-((1H-Pyrrol-2-yl)(p-tolyl)methyl)thiophen-2-
yl)phenyl)(phenyl)methyl)-1H-pyrrole 5a: To a solution of (5-
(3-(hydroxy(4-methoxyphenyl)methyl)phenyl)thiophen-2-yl)(p-
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2
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2H, Ar), 7.35-7.38 (m, 3H, Phenylene and Ar), 7.41 (d, J = 4.1
4
5
6
7
8
9
Hz, 2H, β-Oxa), 7.49-7.55 (m, 7H, β-Thia, and Ar), 7.85-7.86
(m, 1H, Phenylene), 8.16 (bs, 1H, Phenylene); 13C{1H} NMR
(100 MHz, CDCl3): δ = 21.5, 29.8, 55.6, 113.1, 114.1, 115.7,
124.0, 124.3, 127.6, 128.5, 128.7, 129.0, 129.1, 129.2, 129.5,
130.0, 130.3, 130.5, 130.8, 131.3, 132.4, 132.5, 133.8, 134.2,
134.3, 134.5, 135.1, 135.2, 135.3, 135.6, 137.0, 137.1, 137.3,
138.9, 139.5, 142.2, 142.7, 146.7, 151.5, 154.3, 155.27, 160.2,
12.5, 164.0, 168.0, 172.8 ppm; UV-Vis (in CHCl3, λmax/nm, log
ε) = 275 (4.7), 454 (4.7) and 673 (4.1); HRMS (ESI-TOF) m/z:
[M+H]+ calcd for C54H41N2O2S 781.2883, found 781.2884.
REFERENCES
1. (a) Bauer, V. J.; Clive, D. L. J.; Dolphin, D.; Paine III, J. B.;
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Woodward, R. B. Sapphyrins: Novel Aromatic Pentapyrrolic
Macrocycles. J. Am. Chem. Soc. 1983, 105, 6430-6435.
(b)Woodward, R. B. Aromaticity: An International Symposium
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Compound 1b: Compound 1b was prepared by following the
same procedure as given for compound 1a by using
benzitetrapyrrane 5b (100 mg, 0.20 mmol), furan-2,5-diylbis(p-
tolylmethanol) 6 (64 mg, 0.20 mmol), TFA (0.01 mL, 0.02
mmol) and DDQ (107 mg, 0.24 mmol). The crude compound
was purified by alumina column chromatography and obtained
the desired compound 1a using petroleum ether/ ethyl acetate
(90:10) as dark green colored solid (14 mg, 9 % yield). mp:
1
decomposes at ∼120 °C; H NMR (500 MHz, CDCl3): δ = 2.38
(s, 3H, -CH3), 2.40 (s, 3H, -CH3), 2.49 (s, 3H, -CH3), 6.87 (d, J =
4.6 Hz, 2H, β-Py), 6.92 (d, J = 4.4 Hz, 2H, β-Py), 6.98 (d, J = 4.4
Hz, 2H, β-Py), 7.06 (d, J = 4.6 Hz, 2H, β-Py), 7.12-7.15 (m, 3H,
β-Th and Phenylene), 7.19-7.24 (m, 5H, β-Oxa, Ar), 7.31-7.38
(m, 4H, β-Th, Phenylene and Ar), 7.43-7.55 (m, 12H, β-Oxa, and
Ar), 7.87-7.89 (m, 1H, Phenylene), 8.29 (bs, 1H, Phenylene);
13C{1H} NMR (100 MHz, CDCl3): δ = 21.5, 29.8, 114.1, 116.0,
123.8, 124.3, 127.6, 127.7, 128.4, 128.6, 128.7, 129.0, 129.1,
129.2, 130.2, 130.4, 130.5, 130.9, 131.3, 132.1, 132.4, 134.2,
134.3, 135.2, 135.3, 135.8, 137.2, 137.3, 137.4, 138.9, 139.1,
142.0, 142.3, 142.7, 146.0, 151.5, 154.7, 155.1, 163.9, 168.0,
173.3 ppm; UV-Vis (in CHCl3, λmax/nm, log ε) = 275 (4.5), 454
(4.7), 673 (4.1) and 941 (3.4); HRMS (ESI-TOF) m/z: [M+H]+
calcd for C53H39N2OS 751.2778, found 751.2773.
6.
Sessler, J. L.; Tomat, E. Transition-Metal Complexes
ASSOCIATED CONTENT
Supporting Information
of Expanded Porphyrins. Acc. Chem. Res. 2007, 40, 371-379.
7. Chatterjee, T.; Srinivasan, A.; Ravikanth, M.; Chandrashekar,
T. K. Smaragdyrins and Sapphyrins Analogues. Chem. Rev.
2017, 117, 3329-3376.
8. Richter, D. T.; Lash, T. D. Synthesis of Sapphyrins,
Heterosapphyrins, and Carbasapphyrins by
Supporting information for this article is available at http://
pubs.acs.org. It contains characterization data (including HRMS,
1H, and 13C NMR spectra) for all the reported compounds,
absorption and crystallographic data.
a “4 + 1”
approach. J. Org. Chem. 2004, 69, 8842-8850.
AUTHOR INFORMATION
9. Szyszko, B.; Malecki, M.; Berlicka, A.; Bialek, M. J.;
Bialonska, A.; Kupietz, K.; Pacholska-Dudziak, E.; Latos
Grażyński, L. Incorporation of a Phenanthrene Subunit into a
Corresponding Author
*E-mail: ravikanth@chem.iitb.ac.in
Sapphyrin
Framework:
Synthesis
of
Expanded
Notes
Aceneporphyrinoids. Chem. - Eur. J. 2016, 22, 7602-7608.
10. (a) Jeong, S.-D.; Sessler, J. L.; Lynch, V.; Lee, C. –H. Dithia-
The authors declare no competing financial interest.
benzisapphyrin:ꢀ
A
Core-Modified Sapphyrin Bearing
ACKNOWLEDGMENTS
Exocyclic Double Bonds at the meso-positions. J. Am. Chem.
Soc. 2008, 130, 390-391. (b) Sengupta, R.; Thorat, K. G.;
Ravikanth, M. Synthesis of Nonaromatic and Aromatic
Dithia Benzisapphyrins. J. Org. Chem. 2018, 83, 11794-
11803.
This paper is dedicated to Professor C. P. Rao, IIT Bombay.
M.R. thanks the Department of Science and Technology, Govt.
of India (File No. EMR/2015/002196 to M. R), S. K. thanks the
UGC (Ref. No. 23/12/2012(ii)EU-V) for fellowship and K.G.T.
thanks the IIT Bombay India for an Institute Postdoctoral
Fellowship.
11. Lash, T. D. Benziporphyrins, a unique platform for exploring
the aromatic characteristics of porphyrinoid systems. Org.
Biomol. Chem. 2015, 13, 7846-7878.
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