Protonation Dependent Topological Dichotomy of Core Modified Hexaphyrins: Synthesis, Characterization, and Excited State Dynamics

Article abstract of DOI:10.1021/acs.joc.6b02576

Two hitherto unknown core modified hexaphyrin analogues have been synthesized and characterized where the conformational dynamics of these macrocycles in the free base form is achieved by the rotation of thienothiophene units. Further unique property of t

Full text of DOI:10.1021/acs.joc.6b02576

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Article
Protonation Dependent Topological Dichotomy of Core modified
Hexaphyrins: Synthesis, Characterization and Excited State Dynamics
Abhijit Mallick, Juwon Oh, Marcin A. Majewski, Marcin St#pie#, Dongho Kim, and Harapriya Rath
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 15 Dec 2016
Downloaded from http://pubs.acs.org on December 16, 2016
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Protonation Dependent Topological Dichotomy of
Core Modified Hexaphyrins: Synthesis,
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Characterization and Excited State Dynamics
Ϯa
‡a
§
§
‡
Abhijit Mallick, Juwon Oh, Marcin A. Majewski, Marcin Stępień, * Dongho Kim * and
Harapriya Rath Ϯ*
Ϯ
Department of Inorganic Chemistry, Indian Association for the Cultivation of Science,
2A/2B Raja S. C. Mullick Road, Jadavpur, Kolkata 700032(India)
‡
Department of Chemistry, Yonsei University, Seodaemun-gu, Seoul 120-749 (Korea)
§
Wydział Chemii, Uniwersytet Wrocławski, ul. F. Joliot-Curie 14, 50-383 Wrocław, Poland
a
Contributed equally
ichr@iacs.res.in
dongho@yonsei.ac.kr
marcin.stepien@chem.uni.wroc.pl
ABSTRACT
Two hitherto unknown core modified hexaphyrin analogues have been synthesized and
characterized where the conformational dynamics of these macrocycles in the free base form
is achieved by the rotation of thienothiophene units. Further unique property of these
macrocycles is the Hückel-Möbius topological switching. The thermodynamic equilibrium
and kinetics of the interconversion leading to Hückel-Möbius switches has been triggered by
external stimuli such as protonation and/or temperature. We have provided a thorough
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solution-state spectroscopic characterization, solid-state structural evidence combined with
in-depth theoretical calculations to investigate the crucial factors involved in such
interconversion between Hückel and Möbius topologies for these hexaphyrins which will be
useful in designing future new members to expanded porphyrin chemistry.
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INTRODUCTION
The rational design and synthesis of discrete and pre-organized molecular systems with
1
defined topology are of interest due to their ion binding properties and conformational
flexibility and allows one to explore uncharted frontiers in chemistry, biology and other
related areas. Recent years have witnessed a renaissance of interest from synthetic chemists
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in arriving at structurally nontrivial aromatic molecules with nonorientable (Möbius-band) π
surfaces.2e The molecular-orbital description of Möbius aromaticity predicts that singlet
annulenes with 4n electrons are aromatic systems in twisted conformations (with an odd
number of half-twists) where the p orbitals lie on the surface of a Möbius strip, whereas
singlet [4n+2] Möbius molecules would be antiaromatic (the opposite of the Hückel rule).2
Porphyrins and expanded porphyrins serve as a benchmark for extreme manifestations of
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aromaticity, antiaromaticity, pseudo aromaticity, and Möbius aromaticity. Because of their
large conformational flexibility, expanded porphyrins are the best platforms to adopt a
Möbius topology since the large strain induced by the molecular twist is dissipated across the
whole macrocyclic ring system. Thus the initial finding of a Möbius porphyrinoid, A,D-di-p-
benziporphyrin,4a was followed by subsequent reports on other Möbius aromatic
porphyrinoids containing [24] or larger electronic conjugation pathways, which were
stabilized and controlled by various factors, such as metal coordination, temperature, solvent
4
effects, protonation equilibria, and peripheral substitution. Much progress has been made in
these endeavors but much remains unexplored. Hence there is an upsurge in demand for new
synthetic expanded porphyrins for an in-depth study of aromaticity and -conjugation. From
literature reports, it is inferable that in sharp contrast to topographically flat fully conjugated
expanded porphyrins, the propensity of figure-eight twisted geometries towards
conformational fluxionality leads to topological switching from one conformation to another
depending upon the protonation state and metallation.5,6a So far, multi-level switching
behavior in a single macrocyclic entity has not been reported in all-pyrrole expanded
porphyrins 4g and their heterologues containing O, S, Se or Te. 4h, 4i, 6a Experimental
realization of new conformationally flexible expanded porphyrins might provide model
systems for investigating the key issue of topologically controlled aromaticity switching.
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Chart 1. Conformations of 6-H
2
and 7-H discussed in the paper. π-conjugation and NH
2
protons pattern are not shown for clarity
RESULTS AND DISCUSSION
Here we report the successful synthesis of two [32]π heteroannulenes 6-H
2
and 7-H
2
(Scheme
1
). These systems are (1.1.1.1.1.1) hexaphyrin analogues containing two thieno[3,2-
6
b]thiophene subunits (henceforth designated as TT) and six meso bridges, and differ in their
meso substituents adjacent to the TT units (tolyl vs. mesityl). The above design was chosen
with the aim of creating conformationally flexible systems that might exhibit three distinct π-
conjugation topologies depending upon the external stimuli. In an initial step leading to target
macrocycles, thieno[3,2-b]thiophene 1 was synthesized following a literature report.7
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Because the steric bulk of the meso-aryl substituents play a decisive influence on the
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efficiency of macrocyclization, two different tripyrrane analogues 4 and 5 were synthesized
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in two steps from 1 (Scheme S1). The rational synthesis of macrocycles 6-H
2
and 7-H
2
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entailed a mild protic acid-catalyzed condensation of either 4 or 5 with
6
pentafluorobenzaldehyde followed by oxidation with chloranil under reflux. The addition of
0
.1 equivalent of p-toluene sulfonic acid gave the best yield for macrocycles 6-H
2
and 7-H
2
.
Column chromatographic separation over basic alumina followed by repeated silica gel (200-
400 mesh) chromatographic separation yielded the macrocycles 6-H
2
and 7-H in 6% and 8%
2
yields, respectively, as dark green solids.
Scheme1.
Synthesis of macrocycles 6-H
2
, 7-H . Reagents and conditions: i) pyrrole (50
2
equiv), trifluoro acetic acid (1 equiv); ii) pentafluorobenzaldehyde, cat. PTSA, chloranil (2.5
equiv)
The new macrocycles were thoroughly characterized via spectroscopic and single crystal
X-ray diffraction analyses. Macrocycles 6-H
2
and 7-H showed the parent ion peaks at m/z
2
1
416.464 and 1304.156 respectively, under positive ionization in MALDI-TOF mass
spectrometry (Figure S6, S7), thus confirming their elemental composition.
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The expanded macrocycles 6-H
2
and 7-H were anticipated to show considerable
2
conformational flexibility, as previously observed for various expanded porphyrinoids. 4, 5, 6
In both molecules, the structure bears a formal resemblance to A, D-di-p-benzihexaphyrin, 4a,
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because of the presence of two quasi-linear subunits (TT vs. p-phenylene) in the macrocycle.
On the basis of this similarity, a range of conformers were considered for the present ring
systems, to facilitate further analysis. The lower symmetry of the rotatable TT fragments
produces a larger number of distinct conformations that need to be considered, and we found
3
e
it advantageous to classify these structures using the previously reported binary system. In
particular, there are three distinct arrangements of the TT units in the figure-eight Hückel
structure (denoted T2, because of the corresponding linking number Lk = 2).3e,4c In these
arrangements, labeled 0, 96, and 2145 in Chart 1, the non-hydrogen atom framework can
have the limiting point symmetry D
2
, C
2
and D , respectively. Likewise two distinct Möbius
2
T1 structures, 1 and 97, each of C
1
symmetry, can be considered. The symmetry of these
conformations can be further lowered by protonation. In parallel with the spectroscopic work,
we used DFT calculations to systematically analyze the geometries and relative energies for
different protonation states of the above skeletal structures. Relevant results of this analysis
are discussed below (for complete computational data, see the Supporting information).
We have carried out thorough NMR studies in the free base as well as in the protonated
state in order to investigate the relationship between solution-state dynamic conformational
changes and aromaticity in 6-H
2
and 7-H
2
. Dynamic NMR studies support the premise that
depending on the relative orientation of TT units at the crossing point, there are two T2 type
conformers in the free base form of the macrocycle 6-H
2
(Chart 1). The temperature-
1
dependent behavior of the H NMR spectra of free base 6-H
2
in CD Cl indicates an effective
2
2
D symmetry, which is inferred from the equivalence of all mesityl groups and the non-
2
equivalence of mesityl o-Me signals. This symmetry is consistent with a figure-eight Hückel
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structure that does not untwist on the NMR time scale, while undergoing a rapid NH proton
transfer even at 175 K (Figure 1). Below 250 K, decoalescence of the peak at 18.12 ppm
takes place, indicating two forms with different populations (the peaks at 17.75 and 18.61
ppm for major and minor species, respectively). The population of minor form decreases
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upon decreasing temperature (from 0.20 at 220 K to 0.15 at 175 K). The H NMR spectrum
of the major conformer is similar to that at high-temperature spectrum and only a very weak
ROE is observed between NH and TT protons at 190 K, representing the D
(Figure S30). These features are consistent with the orientation of TT units found in the 0
conformation of 6-H (Chart 1). This assignment is further supported by DFT calculations,
which predict the lowest energy for the 37,41H-0-6-H structure (Figure 2, Table 1). In the
2
symmetry
2
2
spectrum of the minor conformer, the peaks at 18.61 ppm (NH) and 9.96 ppm (TT) have
equal integral intensities and show a strong dipolar contact in the ROESY spectrum (Figure
S30). These features correspond to the C
TT subunits is rotated by 180° relative to its position in the 0 structure (Figure 2). The
remaining signals of 96-6-H were difficult to assign because of extensive overlap with the
spectrum of major conformer (in particular, the other TT signal of 96-6-H overlaps
2
-symmetrical conformer 96, in which one of the
2
2
precisely with the TT line of 0-6-H
2
). In accord with the experiment, DFT calculations
predict 38,42H-96-6-H
2
as the second most stable structure (relative ΔG0298 of 0.36
kcal/mol, Table 1).
The T2 topology of the π system in the 0-6-H
2
and 96-6-H conformers corresponds to
2
two half-twists and an orientable surface. For a [32]annulenoid circuit, this topology is
1
expected to produce a Hückel-antiaromatic 4n system. The H chemical shifts are indicative
of a moderate paratropic ring current. At 190 K in DCM-d
by the low-field positions of the inner NHs (17.76 and 18.60 ppm for 0-6-H
and of the unique TT proton of 96-6-H residing in the cavity (9.96 ppm). Outer protons
2
, the paratropicity is demonstrated
2
and 96-6-H ),
2
2
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attached to the macrocycle are moderately affected by the ring current effect (β-CHs in the
5.8–6.2 ppm range). Finally in the Mes substituents, the endo o-Me groups (3.27 ppm in 0-
6
-H
2
) are deshielded relative to those in 5-mesityldipyrrin (2.10 ppm), a feature previously
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shown to indicate paratropicity. 4b
Name[a]
Neutral
Topology and
protonation
SCF E[b]
a.u.
E
[c]
ZPV[d]
a.u.
min. freq.
[e]
ΔG[f]
a.u.
ΔGrel[g]
kcal/mol
rel
–
1
kcal/mol
cm
f_0000_37_41x
f_0000_37_42
f_0001_37_41
f_0001_38_41
f_0096_37_41a
f_0096_37_42
f_0096_38_41
f_0096_38_42a
f_0097_37_41
f_0097_37_42
f_0097_38_41
f_0097_38_42
f_2145_37_41a
f_2145_37_42
Monocations
f_0000
f_0001_37_38_41
f_0001_37_38_42
f_0001_37_41_42
f_0001_38_41_42
f_0096_37_38_41
f_0096_37_38_42
f_0097_37_38_41
f_0097_37_38_42
f_0097_37_41_42
f_0097_38_41_42
f_2145
37,41H-0 -5959.772214
37,42H-0 -5959.755199
37,41H-1 -5959.757331
38,41H-0 -5959.750163
37,41H-96 -5959.769891
37,42H-96 -5959.753658
38,41H-96 -5959.757720
38,42H-96 -5959.769882
37,41H-97 -5959.754737
37,42H-97 -5959.757553
38,41H-97 -5959.753262
38,42H-97 -5959.757536
37,41H-2145 -5959.767270
37,42H-2145 -5959.753887
0.00 1.240085
10.68 1.239838
9.34 1.240305
13.84 1.240189
1.46 1.239991
11.64 1.240012
9.09 1.240223
1.46 1.239894
10.97 1.240038
9.20 1.240140
11.89 1.240297
9.21 1.240427
3.10 1.239846
11.50 1.239799
10.48 -5958.668453
10.24 -5958.648461
8.31 -5958.655465
6.72 -5958.650246
10.60 -5958.666208
8.84 -5958.648597
9.86 -5958.651024
7.42 -5958.667879
3.49 -5958.654846
7.21 -5958.656100
7.39 -5958.653315
7.86 -5958.655437
10.26 -5958.665594
5.80 -5958.651880
0.00
12.55
8.15
11.43
1.41
12.46
10.94
0.36
8.54
7.75
9.50
8.17
1.79
10.40
37,38,41H-0 -5960.217048
37,38,41H-1 -5960.204840
37,38,42H-1 -5960.210743
37,41,42H-1 -5960.207898
38,41,42H-1 -5960.205744
37,38,41H-96 -5960.216025
37,38,42H-96 -5960.214118
37,38,41H-97 -5960.207275
37,38,42H-97 -5960.211155
37,41,42H-97 -5960.208800
38,41,42H-97 -5960.207787
37,38,41H-2145 -5960.212983
0.00 1.254180
7.66 1.254197
3.96 1.254142
5.74 1.254125
7.09 1.254662
0.64 1.254055
1.84 1.253815
6.13 1.254465
3.70 1.254076
5.18 1.253957
5.81 1.254977
2.55 1.254012
9.54 -5959.096765
7.96 -5959.088483
8.88 -5959.094168
7.86 -5959.091944
7.13 -5959.088943
10.39 -5959.098015
9.61 -5959.096644
7.53 -5959.090403
8.20 -5959.095982
7.70 -5959.093433
7.52 -5959.091205
8.82 -5959.098463
1.07
6.26
2.70
4.09
5.97
0.28
1.14
5.06
1.56
3.16
4.55
0.00
Dications
f_0000a
f_0001
f_0096a
f_0097
f_0455
f_2145
37,38,41,42H-0 -5960.648235
-1 -5960.648777
1.00 1.268539
0.66 1.268982
16.41 1.268563
0.00 1.269557
1.45 1.269560
2.44 1.268316
7.85 -5959.514542
7.80 -5959.516470
10.86 -5959.485483
7.74 -5959.516608
8.58 -5959.514093
6.82 -5959.515649
1.30
0.09
19.53
0.00
1.58
0.60
-96 -5960.623683
-97 -5960.649831
-455 -5960.647519
-2145 -5960.645949
Table 1. Computational data for 6-H and its cations.
2
[a] Dataset name (.pdb files). [b] PCM(DCM)/KMLYP/6-31G(d,p) energies for optimized
geometries. [c] Relative energies (separately for each protonation level). [d] Zero-point
vibrational energy. [e] lowest vibrational frequency. [f] Gibbs free energy. [g] Relative Gibbs
free energies (separately for each protonation level).
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1
Figure 1.
Selected regions of variable temperature H NMR spectra of 6-H
2
(CD Cl2,
2
600 MHz)
Importantly, the chemical shift pattern observed for the major form is in good quantitative
agreement with GIAO shieldings calculated for the DFT model of 37,41H-0-6-H at the
2
KMLYP/6-31G(d,p) level of theory (Figure S31). In the present work, it was not possible to
provide complete signal assignment for all species. The completeness of the assignment was
limited in several cases by signal overlap and line broadening.
1
Variable-temperature H NMR measurements performed for 7-H
2
revealed a similar
conformational exchange between the 0 and 96 structures with moderate paratropic ring
current. However, at room temperature, single o-Tol and m-Tol signals were observed,
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corresponding to rapid exchange between the endo and exo positions in the Tol substituents
(
Figures S32, S33). This effect could be caused either by rapid rotation of the Tol groups or
by inversion of the figure-eight twist of the macrocycle. The former explanation is in line
with the reduced steric hindrance of the Tol groups in 7-H . As the rigidity of the macrocycle
should not be significantly affected by the difference of substituents, the barrier to inversion
is expected to be similar in 6-H and 7-H
Single crystals suitable for X-ray diffraction were obtained by slow diffusion of
methanol into toluene solutions of 6-H and 7-H . In the free-base form, macrocycles 6-H
and 7-H (Figures 3a and S58) were each observed to adopt the twisted Hückel 0
conformation prevalent in solution. In the structure of 6-H , the dihedral angle for pyrrolic
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
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0
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0
1
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0
1
2
3
4
5
6
7
8
9
0
2
2
2
.
2
2
2
2
2
ring is 32.66°, for pyrrolenic ring is 24.57° and for thienothiophene moiety is 11.24° with
respect to the mean plane containing the six meso carbons. The distance between the
centroids of the TT units in 6-H
The acid-base chemistry of 6-H
spectrophotometric titrations with trifluoroacetic acid (TFAH) performed in 1, 2-
dichloroethane (DCE, Figure 4). The free base forms of 6-H and 7-H showed major
absorption bands at 320, 517 and 658 nm for 6-H and at 357, 511 and 683 nm for 7-H ,
2
and 7-H
2
were 3.80 Å and 3.78Å respectively.
2
and 7-H was initially investigated using
2
2
2
2
2
respectively, with absorption tailing over 1400 nm. The latter feature is characteristic of
1
antiaromatic porphyrinoids, in line with the observation of T2-type conformers by H NMR
spectroscopy. Both compounds turned out to be relatively weak bases and required a large
excess of acid to undergo protonation. For each species, two well-defined protonation-related
events with two isosbestic points were observed (Figure 4). For 6-H
2
, the two stepwise
, the two
spectral changes exhibit isosbestic points at 547 and 617 nm whereas for 7-H
2
isosbestic points at 543 and 612 nm respectively upon the two stepwise spectral changes. In
the first event, occurring at ca. 20 equiv of TFAH, a species with a broad, strongly NIR-
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shifted Q-like band was observed, with a maximum at 1500 nm and 1700 nm for 6-H and 7-
2
2
H , respectively. For each system, the Soret-like maximum was also red-shifted from ca. 500
2+
]2+
to 600 nm. The calculation results for protonated planar [455-6-H
4
] and [455-7-H
4
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with B3LYP/6-31g** show the forbidden transitions in the NIR region around 1600 nm
(Table S1, Table S2). However, the experimental data show the conspicuous absorption
bands at 1600~1800 nm. Such inconsistency can be attributed to the hydrogen bond
interactions between pyrrolic protons and TFA counter anions. Because 20 equivalents of
TFA are added for changing to [455-6-H
4
]2+ and [455-7-H ]2+, the hydrogen bond
4
interaction may trigger distortion of planar structures and molecular complexes of [455-6-
2+
H
4
] and [455-7-H
]2+ with TFA counter anions which can lead to the intensified lowest
4
absorption bands in the NIR region. In the calculation based on the core macrocycle of
]2+ and [455-7-H ]2+, the forbidden transitions in the NIR region exhibited
[
455-6-H
4
4
increased oscillator strengths when the TFA counter anions are calculated together (Figure
S55). Thus, it is expected that the hydrogen bonding interactions and formation of molecular
complexes lead to the enhanced absorption bands in 1600-1800 nm. An additional reaction
with TFAH could be induced by using a very large excess of acid (300 to 500 equiv). The
resulting absorption spectra were characterized by a major Q-like absorption in the 900-1200
nm range. In addition, fluorescence emission was observed in the NIR region at this stage of
titration (Figure S26). The addition of triethylamine restored quantitatively the free base
forms 6-H
2
and 7-H (Figure S27), indicating the reversibility of the entire acid-induced
2
reaction sequence. Spectrophotometric TFAH titrations of 6-H
2
and 7-H in dichloromethane
2
provided very similar results.
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Figure 2
DFT-optimized geometries for selected conformers and tautomers of 6-H and
2
2
+
[6-H
4
] . Gibbs free energies (PCM(DCM)/KMLYP/6-31G(d,p), kcal/mol, 298 K) are given
relative to 37,41H-0-6-H
2
(for free bases), and relative to [97-6-H
4
]2+ (for dications).
To gain deeper insight into the change of aromaticity by protonation, we investigated
their excited state dynamics by fs-transient absorption (TA) measurements. In line with the
1
changes in the absorption and H NMR spectra of 6-H
2
and 7-H
2
by protonation, their TA
and 7-H
the TA spectra showed the ground state bleaching (GSB) bands at 520 and 512 nm and the
broad excited state absorption (ESA) bands over 550 and 535 nm for 6-H and 7-H
respectively. These TA spectra decayed with two time constants of 0.5 and 15 ps for 6-H and
.4 and 15 ps for 7-H . The rapid and relatively slow decays in the order of fs and tens of ps
suggest the presence of optically dark state typically, which are observed in the TA spectra of
spectra also showed drastic spectral changes (Figures 5 and S28). For free base 6-H
2
2
,
2
2
,
2
0
2
1
0
antiaromatic porphyrinoids. In accordance with the absorption spectra of 6-H
2
and 7-H
2
with 20 equiv. of TFA, their TA spectra also showed red-shifted GSB and ESA bands. The
decay of TA spectra were fitted with the two time constants of 0.2 and 13 ps for 6-H 2+
2+. Compared to the free base forms, the acceleration of fast time
4
and
0
.1 and 14 ps for 7-H
4
constants are attributable to the more effective π-conjugation with enhanced antiaromaticity
on the planar geometries. On the other hand, 6-H and 7-H with 500 equiv. of TFA displayed
2
2
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the typical features of aromatic porphyrinoids in the TA spectra containing strong GSB band
1
0
with weak ESA bands. Moreover, the excited state lifetimes were significantly increased.
Along with their absorption spectra, these observations suggest the Möbius aromatic
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2
+
2+
character of protonated 6-H
4
and 7-H
4
under excess acid condition. Interestingly, in the
comparative analysis between the TA spectra of protonated 6-H 2+
and 7-H
2+
under excess
4
4
acid condition, the clearer TA spectra and longer excited state lifetime were observed for
2+. These differences can also be explained on the basis that the mesityl
protonated 6-H
4
substituents of 6-H
2
induce more rigidity compared to tolyl substituents of 7-H .
2
1
To elucidate the conformational changes attendant upon TFAH addition, H NMR
spectra were recorded for 6-H under diverse sets of conditions involving changes of solvent
(DCM-d , 1,2-DCE-d , acetone-d ), acid concentration (up to ca. 1000 equiv), and
temperature. Upon addition of excess trifluoroacetic acid (19 equiv, as 1% solution in DCM-
2
2
4
6
d
2
, room temperature), dramatic changes in the spectral pattern were observed, consistent
with the formation of a dicationic species, 6-H 2+
(Figures S35-S38).
4
The occurrence of ring inversion was inferred from the observation of two sets of
correlations in 2D COSY spectra (Figure S37), one between a pair of doublets at 16.3–16.9
ppm and another between a pair of doublets at 3.7–3.8 ppm, both corresponding to β-CH
protons of pyrrole rings. The distinction between the inverted pyrrole and non-inverted
1
pyrrole ring β-CH protons was further based on 2D NOESY spectra (Figure S38). The H
2+
NMR spectrum of 6-H
4
at 278 K (Figure 6) showed an NH signal at 22.65 ppm, identified
by D
2
O exchange experiments (Figure S39), which is assumed to correspond to the non-
inverted pyrroles. The NH signal of the inverted pyrrole ring is likely broadened by hydrogen
bonding and could not be located in the spectrum. The spatial proximity between o-methyl
protons of one set of Mes groups (2.04 ppm) with adjacent β-CH protons of the noninverted
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pyrrole ring (3.78 ppm) and outer β-CH proton of the thiophene ring (6.94 ppm) produced the
expected dipolar contacts in the NOESY spectrum, providing unequivocal assignment of the
three signals. Consequently, the signals at 16.37 and 16.90 ppm were assigned to inner β-CH
protons of the inverted pyrrole ring. The peak at 15.31 ppm, which showed no correlation
with any other peak in either COSY or NOESY spectra, was proposed to correspond to the
inner β-CH proton of thiophene. The two distinct singlets at 6.29 ppm and 6.39 ppm have
been assigned to the m-CH protons of two different meso-mesityl rings based on correlations
that each signal shows to o-methyl and p-methyl signals in the 2D COSY spectra (Figure
S37). The observation of inner NH signals at 22.65 ppm is a diagnostic feature of a paratropic
ring current, which is further manifested in the respectively upfield and downfield shifts of
other inner and outer protons attached to the macrocycle. These spectral features could be
rationalized in terms of double pyrrole ring inversion, leading to a quasi-planar conformer
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
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2
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0
1
2
3
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5
6
7
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9
0
[455-6-H
]2+ (Chart 1, Figure 2). An exactly similar NMR spectral pattern has been
4
observed upon addition of excess trifluoroacetic acid (19 equiv, as 1% solution in CDCl
3
,
room temperature), for 7-H
2
consistent with the formation of a dicationic species, 7-H 2+
4
(
Figures S40-S42). Thus, a quasi-planar conformer [455-7-H
4
]2+ with two pyrrole ring
inversion can also be envisaged for 7-H 2+.
4
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Figure 3.
X-ray crystal structure of 6-H in (a) free base, (b) protonated form (a, b: plane
2
view, a′, b′: side view). The thermal ellipsoids were scaled to the 50% probability level.
Further support for the feasibility of the 455 conformer was obtained from an X-ray
crystallographic
][CF CO ·[CF
CF
analysis.
COOH]
Single
crystals
of
a
trifluoroacetate
salt
[6-
H
4
3
2
]
2
3
4
were obtained by diffusion of hexane into the
. The solid-state geometry of 6-H 2+
was quasi-
3
COOH/dichloromethane solution of 6-H
2
4
planar (Figure 3b). There is one centrosymmetric dication in the unit cell, and it is hydrogen-
bonded to two dihydrogen tris(trifluoroacetate) assemblies via the NH hydrogens of inverted
pyrroles (Figure S56). The inverted pyrrole rings deviated more strongly from the mean plane
containing the six meso carbons compared to the noninverted pyrrole rings (13.32° vs. 8.56°).
The largest tilt was however exhibited by the TT units (38.28°).
Interestingly, when a smaller amount of acid (ca. 1 equiv) is addded to the DCM-d
2
1
solution of 6-H
2
, the H NMR spectrum becomes broadened but the positions of peaks remain
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virtually unaltered. Likewise, the initial changes of optical absorption spectra are
insignificant, indicating that the initial figure-eight conformers 6-H are relatively weak bases.
2
The formation of the 455 dication requires a double pyrrole ring inversion and is apparently
0
1
2
3
4
5
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7
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0
not instantaneous. The rate of ring inversion is accelerated by temperature and by the
increasing acid concentration. When a solution of 6-H
equiv of TFAH and immediately cooled down to 210 K, a spectrum with effective D
symmetry was observed (Figure S43), which was clearly distinct from the spectrum of the
455 dication. Conversion of the D intermediate into the 455 species was however
observed when the sample was left to stand at room temperature.
2
in DCM-d was treated with ca. 35
2
2

2
Figure 4.
UV-Vis-NIR absorption spectra of (a) 6-H
2
and (b) 7-H upon TFAH titration
2
in 1, 2-dichloroethane.
The transient low-temperature spectrum showed moderate diatropic characteristics,
1
which could be inferred from H shift values, and was thus assumed to correspond to Möbius-
type T1 conformations (1 and 97) in the limit of fast rotation of TT units. Specifically, the
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β-CH signals were shifted to 7.30 and 7.19 ppm, whereas a broadened peak, assigned as the
TT signal, was found at 5.23 ppm. The latter shift, which is dynamically averaged over four
non-equivalent sites that are present in stationary T1 structures, is consistent with the upfield
relocation previously observed in the symmetry-averaged spectra of A, D-di-p-
benziporphyrin.4a, b The Me-o-Mes signals in the 1/97 species resonate at 2.89 and 0.40 ppm.
While the available 2D NMR data (Figure S44) were insufficient to assign these two peaks,
they are expected to correspond respectively to exo and endo positions, in line with the
previously established shielding effects in A, D-di-p-benziporphyrin.4a, b
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It should be noted that the protonation status of the transient species discussed above
could not be determined at 210 K, but the formation of the dication is considered probable in
the presence of a large acid excess. Below 210 K, the spectrum underwent decoalescence,
consistent with the expected lower symmetries of stationary conformers, but significant line
broadening precluded more detailed analysis of these complex spectral patterns. Stepwise
low-temperature titration of 6-H
considerable complexity, and apparently lower symmetry. DFT-derived ΔG0298 energies
]2+ and [97-6-H ]2+ were very similar (0.09 and 0.00 kcal/mol),
2
with TFA produced intermediate spectral patterns of
calculated for [1-6-H
4
4
indicating that the two conformers may coexist in solution at experimentally available
temperatures. The energy of the quasi-planar 455 system was slightly higher (1.58
kcal/mol). It should be noted, however, that in these calculations, hydrogen-bonded
interactions with carboxylate anions and acid molecules were not included. Such interactions
are expected to be important, especially at high acid concentrations, and have been shown
4
previously to affect the conformational dynamics of expanded porphyrins. Overall, the
above experimental and theoretical data indicate that the T2-type free base of 6-H does not
2
undergo ring inversion when protonated at low temperatures, and the limiting species
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6
generated under excess acid conditions is most likely a mixture of Möbius aromatic [1-6-
2
+
H
4
] and [97-6-H
]2+ dications.
4
0
1
2
3
4
5
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7
8
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1
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7
8
9
0
1
2
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4
5
6
7
8
9
0
Figure 5. fs-Transient absorption spectra and decay profiles (inset) of 6-H with (a) 0, (b) 20
2
and (c) 500 equiv. of TFAH in 1,2-dichloroethane.
1H NMR spectra of [6-H
more than 300 equiv) were found to reveal an effective D
consistent with a diatropic ring current. Such a spectrum was observed in 1, 2-DCE-d
K (Figure S45), when the sample of 6-H was treated with ca. 120 equiv of TFAH. When the
]2+ obtained in the presence of a very large excess of TFAH
symmetry and chemical shifts
at 273
4
(
2
4
2
amount of acid was gradually increased to ca. 1000 equiv the spectrum became sharper. The
1H shifts underwent only minor changes of chemical shifts, likely resulting from interactions
with excess TFAH (final values: β-H 7.21 and 7.15 ppm, TT 5.99 ppm, NH 5.84 ppm). A
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sharp, high symmetry spectrum, with similar shifts (β-H 7.53 and 7.09 ppm, TT 6.37 ppm,
NH not observed, o-Mes 2.85, 0.60, m-Mes 7.20, 6.62, p-Mes 2.23 ppm, Figure S47) was
also observed in acetone-d in the presence of TFAH (ca. 20% v/v). The associated electronic
6
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absorption spectrum was however different in comparison with the DCE experiment: while
the position of the Soret band was preserved, the Q bands were observed in the 800–1000 nm
range in the acetone solution (Figure S24). In acetone-d
6
, exchange cross-peaks between endo
]2+ in the ROESY spectrum
and exo positions of the Mes group were observed for [6-H
4
(Figure S49), indicating a slow untwisting of the figure-eight structure. On lowering the
temperature, gradual line broadening was observed, but the symmetry of the spectrum
remained unchanged down to 170 K.
1
]2+ observed in the presence of a large acid excess is
The H NMR spectrum of [6-H
4
very similar to that observed for the transient 1/97 conformer generated at low temperature,
and it is tempting to suggest that the conformation of the high excess acid species might in
1
fact be the same. While such an interpretation is most likely, it should be noticed that the H
NMR spectrum is in all cases being observed in the limit of fast exchange, and exact
structures of these conformers are not accessible. In particular, the conformational changes
induced at different acid concentrations may involve not only rotations of TT units (which
generate the 0, 1, 96, 97, 2145 conformers, and are sufficient to induce topology switching)
but also additional twists of the macrocycle near pyrrole rings. As long as such a twist does
not lead to a complete inversion of the figure-eight structure, a D
2
symmetric spectrum is
1
expected in the fast exchange limit. Nevertheless, the symmetry-averaged H shifts observed
at high acid concentrations are consistent with a moderately diatropic structure, as indicated
by the downfield positions of β-H signals (δ > 7 ppm), and the unusually upfield position of
the TT signal. The latter change is similar to that observed for the p-phenylene signal in the
1
4a
H NMR spectrum of A,D-di-p-benzihexaphyrin , and may thus indicate a Möbius-type T1
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1
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2
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2
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2
2
2
2
2
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5
5
5
5
5
6
1
]2+ measured in
conformer. In line with the latter conjecture, the H NMR shifts of [6-H
4
acetone-d
6
are in a semi-quantitative yet still remarkably good agreement with the D
2
-
]2+ (Figure
averaged GIAO shieldings calculated for the lowest-energy dication 97-[6-H
4
0
1
2
3
4
5
6
7
8
9
0
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7
8
9
0
S50). In particular, the calculation correctly reproduces the downfield relocations of β-H
signals and the upfield position of TT (7.02 ppm), relative to the T2 free base.
The conformational change observed at different acid concentrations is most likely
2
+
promoted by association of TFA anions and TFAH molecules to the [6-H ] , in analogy to
4
the behavior observed for A,D-di-p-benziporphyrin in the presence of dichloroacetic acid.4b
However, since the present system is observed only in the fast exchange limit, the exchange
between bulk and associated acid molecules and anions results in the complete loss of any
1
structural information related to the acid binding and symmetry averaging of the H NMR
2
+
spectral pattern of [6-H ] .
4
In different solvents and at different acid concentrations, the stationary geometries are
likely to differ because of hydrogen-bonded interactions with TFAH molecules. Acid
4b
association in solution was previously demonstrated for A,D-di-p-benzihexaphyrin as well
4
as for other porphyrinoid systems. Association with TFAH is expected to be significantly
stronger in DCE (and DCM) than in acetone, because of the higher polarity of the latter
2
+
solvent, and may explain why the absorption spectrum of [6-H ] in acetone is different.
4
2+
Figure 6.
1H NMR spectrum of protonated 6-H
4
in CD
2
Cl at 278 K.
2
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Scheme 2.
Acid-base and conformational behavior of 6-H in 1, 2- DCE.
2
The conformational behavior of 6-H
summarized in Scheme 2. When the protonation is performed at low temperatures (below ca.
73 K with rapid acid addition), the figure-eight twist of the macrocycle is preserved, and the
2
in DCE at various acid concentrations is
2
system goes from the T2 free base structure (the 0/96 equilibrium mixture) via an
unspecified mixture of T2 and T1 conformations at the monocation level to the predominantly
T1-type dication. The spectral symmetry of this species and its diatropic character are
retained over a wide range of acid concentrations, implying that the conformation is
preserved. However, extensive association with acid molecules is indirectly observed above
1
00 equiv of TFAH. When 6-H
2
is titrated at room temperature, the dication undergoes
]2+
double pyrrole inversion in the initial titration phase, to yield the quasi-planar [455-6-H
4
species. The latter conformer is stable up to ca. 20 equiv of TFAH, but it reverts to the figure-
2
+
eight Möbius structure [1/97-6-H
4
] , when more acid is added. A qualitatively similar
behavior was observed for 7-H upon titration with TFAH in dichloromethane-d
2
2
(Figure
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6
S51), but the system was less amenable to 2D spectral analysis (Figure S53). A spectrum
2
+
clearly corresponding to the T2 conformer [455-7-H ] was observed at intermediate acid
4
concentrations. In the presence of a large excess of TFAH, the appearance of the spectrum
0
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indicated the presence of multiple forms. The major species observed at 263−243 K (Figure
S52) could however be identified as a D -symmetric diatropic structure β-pyrroles: 8.06, 7.96
2
ppm, TT 5.87 ppm, Figure S54). In particular, this species features a single set of signals
corresponding to a slowly rotating Tol substituent (ortho 8.13, 6.21 ppm, meta 7.28, 7.11
ppm, p-Me 2.33 ppm). This result is again consistent with the prevalence of a Möbius species
at high acid concentrations proposed above for 7-H on the basis of TA spectroscopy.
2
CONCLUSION
In conclusion, the present manuscript provides many insights into the conformational
behavior of a highly twisted fused [32] heteroannulene associated with various topologies.
Excellent agreement between the theoretically determined properties and the experimental
spectroscopic measurements are key to the evidence of weak twisted-Hückel antiaromatic,
strongly Hückel antiaromatic and Möbius aromatic states respectively upon stepwise
protonation. Our results are in accordance with the fact that protonation disrupts
intramolecular H-bonding thereby leading to topological dichotomy in order for the
macrocycle to gain aromatic stabilization energy. Further development of dynamic
heteroannulenes is currently under progress in our laboratory.
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EXPERIMENTAL SECTION
Materials and Methods:
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Electronic absorption spectra were measured with a UV-vis-NIR spectrophotometer, and
1
13
variable temperature UV-vis-NIR were carried out in cryostat. H, and C NMR spectra were
1
13
recorded on a spectrometer (operating as 600.17 MHz for H and 150.91 MHz for C) using
1
the residual solvents as the internal references for H [(CHCl
3
(δ = 7.26 ppm), CH
2
Cl (δ =
2
5.32 ppm), Acetone (δ = 2.04 ppm) and DCE (δ = 3.72 ppm)].
High-resolution electrospray ionization time-of-flight mass spectroscopy (HR-ESI-TOF MS)
was conducted by using the positive mode for an acetonitrile solution of samples. All
solvents and chemicals were of reagent grade quality, obtained commercially and used
without further purification except as noted. For spectral measurements, anhydrous
dichloromethane was obtained by refluxing and distillation over CaH
obtained by refluxing and distillation over pressed Sodium metal. Thin layer chromatography
TLC) was carried out on alumina sheets coated with silica gel 60 F254 and gravity column
2
. Dry THF was
(
chromatography were performed using Silica Gel 230-400 mesh.
X-Ray structure determination
Crystallographic data were collected at 100 K by using graphite-monochromated Mo-Kα (λ =
0
.71073Å). The structures were solved by SHELX-2014 using SHELXTL suite of
programme. The final refinement of the structure was carried out using least-squares method
2
on F using SHELXL-2014. The final refinement of the solved structure converged at the R
value of 0.0856 (I>2σ (I)) for free base form of 6-H
2
and R value of 0.0737 (I>2σ (I)) for
2
+
protonated form of 6-H
4
and R value of 0.0677 (I>2σ (I)) for free base 7-H . All non-
2
hydrogen atoms were refined anisotropically. All the hydrogen atoms were located from
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difference Fourier maps. For protonated 6-H
4
2+, ALERT 2A, 2B arises from potentially
disordered solvent molecules. We tried to fix by using PART command, however atomic
displacement values didn’t reduce.
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Femtosecond transient absorption measurements
The femtosecond transient absorption (fs-TA) spectra were measured with a spectrometer
consisting of two independently tunable homemade optical parametric amplifiers (OPSs)
pumped by a regeneratively amplified Ti: sapphire laser system operating at a repetition rate
of 1 kHz and an optical detection system.
Theoretical Calculation
Density functional theory (DFT) calculations were performed using Gaussian 09.11 DFT
geometry optimizations were carried out in unconstrained C symmetry, using molecular
1
mechanics or semiempirical models as starting geometries. DFT geometries were refined to
meet standard convergence criteria, and the existence of a local minimum was verified by a
normal mode frequency calculation. DFT calculations were performed using the KMLYP
1
2
functional
and the 6-31G (d, p) basis set. PCM solvation (dichloromethane
parameterization) was included in all calculations. NMR chemical shifts were calculated
using the GIAO/KMLYP/6-31G (d, p) level of theory. The absolute shielding of TMS
calculated at the KMLYP level of theory was 31.946 ppm. Electronic absorption spectra were
calculated using time-dependent DFT in the Tamm–Dancoff approximation, using the
B3LYP functional and dichloromethane solvation. Up to 50 transitions were calculated,
providing full coverage of the NIR and visible regions.
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SYNTHESIS
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60
Thieno[3,2-b]thiophene (1): This was synthesized as reported in literature.
1
Yield: 60 %. Colourless crystalline solid. M.p. 53-58 C. H NMR (300 MHz, CDCl
3
): 
1
3
[
ppm]: 7.26-7.28 (d, 2H, J = 4.8 Hz); 7.38-7.40 (d, 2H, J = 5 Hz). C NMR (75 MHz, CDCl ,
3
300K,  [ppm]): 119.6, 127.6, 139.7. HR-ESI-TOF MS (m/z): Found 162.9631 [M+Na]+
+
(
Calcd. 162.9647 for C
H
6 4
S
2
Na ). Anal. Calcd for C
6
H
4
2
S : C, 51.39; H, 2.88. Found: C,
5
1.41; H, 2.90.
(
2, 5-Bis (mesitylhydroxymethyl)-thieno [3, 2-b]thiophene
(2): To a 250 mL round-bottomed flask equipped with a magnetic bar, thieno [3, 2-b]
thiophene 5 (1 g, 7.13 mmol) was placed followed by dry THF (40 mL). The reaction
mixture was stirred under inert atmosphere. N, N, N′, N′-Tetramethyl ethylenediamine (3.2
mL, 0.021 mol) was added followed by stirring for half an hour at room temperature.
Afterward n-BuLi in hexane (1.6 M) (13.04 mL, 0.021 mol) was added through rubber septa
drop wise, yellow turbidity started forming. The reaction mixture was stirred at room
o
temperature for 2 hours and then heated to 66 C for 1 hour. The reaction mixture was
brought room temperature after which it was brought to ice cold temperature. At ice cold
temperature, Mesitaldehyde (2.62 mL, 0.017 mol) in dry THF (40 mL) was then added drop
wise to the reaction mixture, the reaction mixture was stirred for 2 hours. The reaction
mixture was quenched by saturated NH Cl (aq) solution, product was extracted by diethyl
4
ether, dried over Na
2
SO
4
. The crude product was precipitated out by hexane and purified by
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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5
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5
5
6
silica gel column chromatography using ethyl acetate-hexane (1:4) solution. The solvent was
evaporated and light yellow solid was obtained.
1
Yield 2.09 g (67%). M.p. 156 C. H NMR (500 MHz, CDCl3, 300K,  [ppm]): 2.28 (s,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
6
H); 2.33 (s, 12H); 6.46 (s, 2H); 6.71 (s, 2H); 6.87 (s, 4H); CNMR (125 MHz, CDCl
3
,
300K,  [ppm]): 20.6, 29.8, 69.8, 116.4, 130.2, 135.3, 137.0, 137.9, 138.3, 148.8. HR-ESI-
+
+
TOF MS (m/z): Found 459.1430 [M+Na] (Calcd. 459.1423 for [C26
H
28
O
2
S Na] ). Anal.
2
Calcd for C26 : C, 71.52; H, 6.46. Found: C, 71.50; H, 6.44.
H
28
O S
2 2
(2,5-Bis(tolylhydroxymethyl)-thieno[3,2-b]thiophene (3):To
a 250 mL round-bottomed flask equipped with a magnetic bar, thieno[3,2-b]thiophene 5 (1 g,
.13mmol) was placed followed by dry THF (40 mL). The reaction mixture was stirred
7
under inert atmosphere. N, N, N′, N′-Tetramethyl ethylenediamine (3.2 mL, 0.021 mol) was
added followed by stirring for half an hour at room temperature. Afterward n-BuLi in hexane
(
1.6 M) (13.04 mL, 0.021 mol) was added through rubber septa drop wise, yellow turbidity
started forming. The reaction mixture was stirred at room temperature for 2 hours and then
o
heated to 66 C for 1hour. The reaction mixture was brought room temperature after which it
was brought to ice cold temperature. At ice cold temperature, p-tolylaldehyde (2 mL, 0.017
mol) in dry THF (40 mL) was then added drop wise to the reaction mixture, the reaction
mixture was stirred for 2 hours. The reaction mixture was quenched by saturated NH
4
Cl (aq)
solution, product was extracted by diethyl ether, dried over Na SO . The crude product was
2
4
precipitate out by hexane and purified by silica gel column chromatography using ethyl
acetate-hexane (1:4) solution. The solvent was evaporated and light yellow solid was
obtained.
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5
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7
8
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1
Yield 2.09 g (77.5%). M.p. 135 C. H NMR (500 MHz, CDCl
3
, 300K,  [ppm]): 2.35 (s,
3
3
6H); 6.02 (s, 2H); 6.97 (s, 2H); 7.17-7.18 (d, 4H, J = 8 Hz); 7.33-7.34 (d, 4H, J = 8 Hz).
13CNMR (125 MHz, CDCl
, 300K,  [ppm]): 29.8, 73.1, 117.5, 126.4, 129.3, 138.1, 138.3,
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
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44
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46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
+
139.6, 150.1. HR-ESI-TOF MS (m/z): Found 403.0793 [M+Na] (Calcd. 403.0797 for
+
[C
22
H
20
O
2
S
2
Na] ). Anal. Calcd for C22
H
20
O
2
S : C, 69.44; H, 5.30. Found: C, 69.46; H, 5.32.
2
2
-(mesityl (1H-pyrrole-2-yl) methyl) thieno[3, 2-
b]thiophene-5-yl) methyl)-1H-pyrrole (4): Compound 2 (1g, 2.29 mmol) was dissolved in
pyrrole (15 mL, 0.19 mol). The solution was stirred for 45 minutes under nitrogen
atmosphere at room temperature. Trifluoroacetic acid (0.05 mL, 0.22 mmol) was added and
stirred for 1hour. The reaction mixture was quenched by dichloromethane; product was
neutralized by NaOH (aq) solution, extracted by dichloromethane, dried over Na
2
SO and
4
dried in rotary evaporator to give yellow oil. The crude product was purified by silica gel
chromatography using 10% ethylacetate-hexane mixture. Compound 4 was obtained as light
yellow foam.
1
Yield 0.702 g (57%). H NMR (500 MHz, CDCl
3
, 300K,  [ppm]): 2.03 (s, 6H, -Me); 2.29-
2
.35 (s, 12H, -Me); 4.24 (s, 2H,-CH); 6.03 (br, 1H, β-H of pyrrole); 6.13 (s, 1H, β-H of
thienothiophene); 6.23 (d, 1H, J = 4.5 Hz, β-H of pyrrole); 6.30 (d, 1H, J = 4.5 Hz, β-H of
pyrrole); 6.54 (br, 1H, β-H of pyrrole); 6.69 (s, 1H, β-H of thienothiophene); 6.70-6.71 (m,
1
H, β-H of pyrrole), 6.72-6.73 (m, 1H, β-H of pyrrole); 6.86 (s, 2H, Mesityl-CH); 6.92 (s,
1
3
2H, Mesityl-CH); 7.99 (br, 1H, -NH); 8.50 (br, 1H, -NH). CNMR (125 MHz, CDCl ,
3
3
00K,  [ppm]): 20.1, 20.7, 20.9, 21.1, 30.8, 41.2, 107.4, 108.5, 109.2, 109.4, 117.0, 117.4,
1
18.9, 124.7, 126.3, 129.2, 130.6, 133.3, 134.0, 135.9, 136.4, 136.5, 136.8, 137.0, 137.1,
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2
2
2
2
2
2
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4
4
4
4
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5
5
5
5
5
5
5
5
5
6
+
1
37.2, 137.5, 145.5. HR-ESI-TOF MS (m/z): Found 534.2145 [M ] (Calcd. 534.2163 for
[C
34
H
34
N
2
S
2
]+). Anal. Calcd for C34
H
34
N
2
S : C, 76.36; H, 6.41, N, 5.24. Found: C, 76.39; H,
2
6
.45; N, 5.20.
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8
9
0
2
-(tolyl (1H-pyrrole-2-yl) methyl) thieno[3, 2-b]thiophene-5-
yl) methyl)-1H-pyrrole (5): Following the synthetic procedure described for 4, 5 was
obtained starting from 3.
1
Yield 0.895 g (81%). H NMR (500 MHz, CDCl
3
, 300K,  [ppm]): 2. 38 (s, 6H, -Me); 5.63
(s, 2H, -CH); 5.97 (br, 2H, β-H of pyrrole); 6.86 (s, 2H, β-H of thienothiophene); 6.69 (d, 2H,
J = 4.5 Hz, β-H of pyrrole); 6.70 (d, 2H, J = 4.5 Hz, β-H of pyrrole); 7.16 (d, 4H, J = 10 Hz,
1
3
CH–Tolyl); 7.12 (d, 4H, J = 10 Hz, CH–Tolyl); 7.91 (br, 2H, -NH). CNMR (125 MHz,
CDCl
3
, 300K,  [ppm]): 21.2, 46.5, 107.8, 108.6, 117.3, 118.4, 128.4, 129.4, 132.9, 137.0,
+
1
37.8, 139.5, 148.7. HR-ESI-TOF MS (m/z): Found 478.1567 [M ] (Calcd. 478.1537 for
[C30
H
26
N
2
S
2
]+). Anal. Calcd for C30
H
26
N
2
S : C, 75.28; H, 5.47; N, 5.85. Found: C, 75.29; H,
2
5
.49; N, 5.84.
General synthetic procedure of Compound 6-H
condition a solution of 534mg of compound 4 (1mmol) and pentafluorobenzaldehyde
0.12mL, 1mmol) in 250 mL dry dichloromethane was stirred for 30 minutes. Afterward,
2
: Under nitrogen atmosphere and in dark
(
catalytic amount of p-TSA (95mg) was added to the reaction mixture and stirred at RT for 90
minutes. Then chloranil (490mg, 1.99 mmol) was added and opened to air and the mixture
was refluxed for another 1 hour. The solvent was removed under reduced pressure and
compound was filtered by basic alumina followed by repeated silica gel column
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chromatography with the mixture of 40% dichloromethane - hexane solution. After
recrystallization, the title compound was yielded as dark red crystal.
Yield.~85mg (~6%). M.p.>350 °C. MALDI-TOF MS (m/z): Found 1416.3415 (Calcd.
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19
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26
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43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
]+). UV-VIS (CH
-1
-1
3
1
5
6
416.3385 for [C82
H
58
F
10
N
4
S
4
2
Cl
2
, λ [nm], (ϵ [M cm x10 ]), 298K):
17(43.79); 658 (8.56). Anal. Calcd for C82
9.48; H, 4.15; N, 3.93.
H
58
F
10
N S
4 4
: C, 69.47; H, 4.12; N, 3.95. Found: C,
1H NMR (600 MHz, CD
Cl
, 193 K,  [ppm], TMS): 1.45 (s, exo-o-Mes), 2.41 (s, p-CH );
2
2
3
3.27 (s, endo- o-Mes); 5.81 (brs, pyrrole -H); 6.62 (brs, pyrrole -H) ;6,87 (brs, exo-m-
Mes); 7.20 (s, -CH TT); 7.47 (brs, endo-m-Mes)); 9.96 (s, TT -H <96>); 17.75 (brs, s,
<0>NH); 18.61 (s, <96>NH).
1H NMR (600 MHz, 1% CF
s, p-CH ); 1.86 (s, p-CH ); 2.04 (s, o-CH
4.2, 1H, pyrrole -H); 6.29 (s, -CH mesityl); 6.39 (s, -CH mesityl); 6.94 (s, TT -H); 16.37
brs, pyrrole -H); 16.90 (brs, pyrrole -H); 17.21 (s, TT -H); 22.52 (s, -NH).
COOH/CD
Cl
3
2
2
, 273 K,  [ppm], TMS): 1.70 (s, o-CH ); 1.81
3
(
3
3
3
); 3.78 (d, J = 3.5, 1H, pyrrole -H) ; 3.88 (d, J
=
(
General synthetic procedure of Compound 7-H : Under nitrogen atmosphere and in dark
2
condition a solution of 478 mg of compound 5 (1mmol) and pentafluorobenzaldehyde (0.12
mL, 1mmol) in 250 mL dry dichloromethane was stirred for 30 minutes. Afterward, catalytic
amount of p-TSA (95 mg) was added to the reaction mixture and stirred at RT for 90 minutes.
Then chloranil (490 mg, 1.99 mmol) was added and opened to air and the mixture was
refluxed for another 1 hour. The solvent was removed under reduced pressure and compound
was filtered by basic alumina followed by repeated silica gel column chromatography with
the mixture of 40% dichloromethane - hexane solution. After recrystallization, the title
compound was yielded as dark red crystal.
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