An Isosteric Triaza Analogue of a Polycyclic Aromatic Hydrocarbon Monkey Saddle

Article abstract of DOI:10.1002/chem.202002826

Since a few years, the interest in negatively-curved fused polycyclic aromatic hydrocarbons (PAHs) has significantly increased. Recently, the first chiral negatively-curved PAH with the topology of a monkey saddle was introduced. Herein the synthesis of its triaza congener is reported. The influence of this CH?N exchange on photophysical and electrochemical properties is studied as well as the isomerization process of the enantiomers. The aza analogue has a significantly higher inversion barrier, which makes it easier to handle at room temperature. All experimental results are underpinned by theoretical DFT calculations.

Full text of DOI:10.1002/chem.202002826

Accepted Article
Accepted Article
Title: An Isosteric Triaza Analogue of a Polycyclic Aromatic
Hydrocarbon Monkey Saddle
Authors: Michael Mastalerz, Tobias Kirschbaum, and Frank Rominger
This manuscript has been accepted after peer review and appears as an
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To be cited as: Chem. Eur. J. 10.1002/chem.202002826
Link to VoR: https://doi.org/10.1002/chem.202002826
01/2020

10.1002/chem.202002826
Chemistry - A European Journal
COMMUNICATION
An Isosteric Triaza Analogue of a Polycyclic Aromatic
Hydrocarbon Monkey Saddle
Tobias Kirschbaum,[a] Frank Rominger,[a] and Michael Mastalerz*[a]
Dedicated to Prof. Dr. Günter Helmchen on the occasion of his 80th birthday
[a]
M. Sc. T. Kirschbaum, Dr. F. Rominger, Prof. Dr. M. Mastalerz
Organisch-Chemisches Institut
Ruprecht-Karls-Universität Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg. Germany
E-mail: michael.mastalerz@oci.uni-heidelberg.de
Supporting information for this article is given via a link at the end of the document.
Abstract: Since a few years, the interest in negatively curved fused
polycyclic aromatic hydrocarbons (PAHs) has significantly increased.
Recently, the first chiral negatively curved PAH with the topology of a
monkey saddle was introduced. Herein the synthesis of its triaza
congener is reported. The influence of this CH↔N exchange on
photophysical and electrochemical properties is studied as well as
isomerization process of the enantiomers. The aza analogue has a
significantly higher inversion barrier, which makes it easier to handle
at room temperature. All experimental results are underpinned by
theoretical DFT calculations.
examples of positively curved buckybowls and related structures,
containing N-heterocyclic subunits.[15, 17] Most of these structures
include pyrrole rings and therefore it is not surprising that for the
majority of those structures no isosterical pure CH-analogues are
known to compare properties, such it is e.g. the case for planar
acenes and heteroacenes.[18] A rare exception is the couple
19]
sumanene-triazasumanene,[17q,
whereas
isosteric
azacorannulenes seem not to be stable and decompose to other
products, accompanied by the loss of curvature.[17b, 20] To the best
of our knowledge, for negatively curved PAHs, no such isosteric
couple was described to date.
The interest in curved polycyclic aromatic hydrocarbons (PAHs)
has increased significantly in the last years.[1] One can distinguish
between positively and negatively curved PAHs. The positively
curved PAHs, such as fullerenes, corannulene or other
buckybowls, usually contain one or more pentagonal besides
hexagonal rings.[2],[3] In contrast, those PAHs with a negative
curvature are generated by the incorporation of heptagonal or
octagonal rings.[1c, 4],[5],[6] The simplest negatively curved PAH is
[7]-circulene, which were first time synthesized in 1988 by
Yamamoto et al.[7] The next higher homologue with negative
curvature, the [8]-circulene was not synthesized yet, but in 2013
a larger derivative, the tetrabenzo[8]circulene was presented.[5b-d]
Since then the field experienced a real renaissance.[1] Contorted
PAHs are more soluble than their comparable planar congeners,
because packing of those molecules by tight π-stacking is largely
reduced to the intrinsic curvature. Furthermore, photophysical
and electrochemical properties of contorted PAHs are different
than those of planar compounds, and significantly depending on
the degree of contortion.[8],[9] Last but not least, such as planar
PAHs are molecular precise cutout structures of graphene,
curved PAHs are cutout structures of three-dimensional
conjugated PAHs, such as Mackay crystals,[10] with distinguished
new materials properties.[11] Similar as smaller planar PAHs can
be reacted in a controlled manner to larger ones or graphene
nanoribbons (GNRs),[12] contorted PAHs in principle can be
reacted to curved fully conjugated PAH cages or even to well-
ordered crystals. No doubt, these goals are synthetically quite
challenging, but offer the exploration of new types of conjugated
molecules and materials with yet unprecedented properties.[13]
In contrast to planar PAHs, contorted PAHs with N-
heterocyclic units are much rarer.[14],[15],[16] There have been a few
Figure 1. Comparison of DFT calculated molecular orbitals (B3LYP/6-
311G(d,p)) of monkey saddle PAH 1 and aza-monkey saddle PAH 2.
Recently we introduced the first monkey saddle shaped
PAH 1 (we will abbreviate this compound as CH-MS 1), which is
4a, 4j-l]
conformationally[1c,
stable at ambient conditions.[21] This
monkey saddle PAH consists besides seven hexagons, of three
1
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pentagonal and three octagonal rings. Among all possible
isosteric C3-symmetric triaza monkey saddle PAHs (for detailed
analysis of frontier molecular orbital energies, see Supporting
Information), the largest difference in stabilization of HOMO and
LUMO energies is found for the aza monkey saddle 2 (we will
abbreviate this compound as aza-MS 2), where the nitrogen is
part of the eight membered ring (Figure 1). In contrast to 1, the
LUMO for 2 is lowered about -0.48 eV from -1.90 eV to -2.38 eV
and the HOMO from -5.23 eV to -5.64 eV. Note that for 1, two
energetically degenerated HOMOs and one HOMO-1 are
calculated, whereas for aza-MS 2, this situation switches: Here
we have only one HOMO and two degenerated HOMO-1 levels (-
5.71 eV). By calculations of the AICD-plot and NICS values it is
suggested that ring currents of several rings change only marginal
and thus the overall stability of aza-MS 2 is comparable to that of
the hydrocarbon congener 1 (see Table S2 and Fig. S36 in the
Supporting Information).
space group P21/c. Most interesting is the comparison of the
degree of contortion with that of the CH-MS 1.[21] The angle
between the unsubstituted rings and the central one is between
41.9º and 48.1º. Between the hexyloxy substituted rings and the
central ring the angles are between 29.0º and 36.4º.These values
are very similar to the ones observed for the hydrocarbon monkey
saddle 1 (40.6 to 52.9º and 28.1 to 33.6º). This extraordinary
structural similarity predestines this pair of compounds to study
the isosterical exchange of one CH unit by nitrogen on molecular
properties for negatively contorted PAHs.
a)
b)
Aza-MS 2 was synthesized in two steps from bromotruxene 3[21]
(Scheme 1), which was oxidized with oxygen in the presence of
K2CO3 in DMF to the corresponding truxenone 4 (62% yield).[22]
The second and final step was a cross-coupling with the HCl salt
of aniline boronic acid 5, followed by treatment with acetic acid
c)
d)
o
(10 vol%) in CHCl3 at 80 C to give the title compound 2 after
column chromatography as a bright orange powder in 47%
isolated yield (over both steps). Aza-MS 2 was fully characterized
(for details, see Supporting Information). Besides NMR spectra,
the MALDI TOF MS gave the information of a successful
formation of 2 by a fitting peak at m/z = 904.4482 [M+H]+. In the
IR spectrum no stretching band for a C=O is found, instead a clear
band at 1645 cm-1 was detected, which is in the typical range of
C=N imine vibrations.
Figure 2. Single-crystal X-ray structures of a) bromotruxenone 4 and b-d) aza-
MS 2. In a, only the (M,M,M)- enantiomer and in b) and c) only the (Sa,Sa,Sa)-
enantiomer is depicted. d) packing of aza-MS 2 in the unit cell. (Sa,Sa,Sa)
enantiomers are displayed in yellow and (Ra,Ra,Ra) in blue. In all structures,
solvent molecules and hydrogen atoms are omitted as well as the
hexyloxychains reduced to the first carbon connected to oxygen for clarity.
120
100
80
60
40
20
0
250
300
350
400
450
500
550
600
650
700
wavelength [nm]
Scheme 1. Synthesis of aza monkey saddle PAH 2. a) O2, K2CO3, DMF, 40 oC,
96 h; b) 5 mol% Pd2dba3, 20 mol% H(tBu)3PBF4, 21 equiv. K2CO3, THF/H2O
(1:1 v/v), 80 oC, 48 h; c) 10 vol% AcOH, CHCl3, 80 oC, 18 h.
Figure 3. Comparison of UV/vis of CH-MS 1 (black) and aza-MS 2 (blue) in
CH2Cl2, before and after addition of TFA (1 grey; red 2).
The UV/vis spectrum in CH2Cl2 of the aza-MS 2 is a bit less
pronounced than the one of CH-MS 1 (Figure 3). It shows three
maxima at λ1 = 273 nm (ε1 = 63516 M-1 cm-1), λ2 = 316 nm (ε2 =
26900 M-1 cm-1), and λ3 = 414 nm (ε3 = 13631 M-1 cm-1). The onset
From both, bromotruxenone 4 and the aza-MS 2 single crystals of
high quality were obtained (Fig. 2). Bromotruxenone 4 crystallized
in the orthorhombic space group Pbca. Due to steric repulsion of
the bromo and the carbonyl oxo atoms (average dBr-O = 3.03 Å)
the molecule is triply helically twisted out of plain about 47º. Both
(M,M,M) and (P,P,P) enantiomers are found. The aza-MS 2
crystallized as racemic crystal with both enantiomers (Ra,Ra,Ra)
and (Sa,Sa,Sa) found in the asymmetric unit of the monoclinic
is in comparison to 1 slightly bathochromically shifted to λonset
520 nm, which corresponds to an optical bandgap of Egap,opt = 2.4
eV, which is negligible smaller than for 1 (Egap,opt = 2.5 eV; λonset
=
=
490 nm) and follows the trend of the DFT calculation (see above).
In a mixture of DCM/TFA, the solution of MS 2 became pale red
2
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10.1002/chem.202002826
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and showed a broadening of the longest wavelength peak shifting
bathochromic to an onset at λonset = 710 nm, which can be
explained by protonation of the three sp2-hybridized nitrogens of
the azocine rings. The protonation is reversible. By addition of an
excess of triethylamine the spectrum matches the original one
(see Supporting Information). As expected, the addition of TFA
has no effect to the adsorption spectrum of CH-MS 1.
(Ra,Ra,Ra)
(Sa,Sa,Sa)
100
50
0
Both monkey saddle PAHs were compared by cyclovoltammetry
under the same conditions (for details see Supporting
Information). The CH-MS 1 shows an irreversible oxidation at
+0.65 V, whereas the aza-MS 2 is oxidized at higher potentials
(+0.85 V). This corresponds to ionization potentials of -5.45 eV (1)
and -5.65 eV (2) and matches the trend of the DFT calculated
stabilization of the HOMO. The first reduction potential of CH-MS
1 is found at -1.8 V (electron affinity = -3.0 eV) and that of the aza-
MS 2 at -1.5 V (-3.3 eV). The electrochemical band gaps of
Egap,CV= 2.5 eV (1) and Egap,CV = 2.4 eV (2) are the same as the
optical ones.
-50
-100
200
250
300
350
400
450
500
550
600
wavelength [nm]
Figure 5. CD spectra of the enantiopure aza-MS 2 (n-heptane, (Ra,Ra,Ra):
25 µM, (Sa,Sa,Sa): 21 µM). Assignment of absolute stereochemistry according
to TD-DFT calculations (Supporting Information).
The event of racemisation of the aza-MS 2 was also investigated
by DFT calculations (Fig. 6) and compared to that of the CH-MS
1. As for 1, it also is most likely a step-wise mechanism via several
twisted transition states rather than via a planar one (not depicted).
Starting from enantiopure (Sa,Sa,Sa)-2 the first transition state to
intermediate (Sa,Sa,Ra)-2 is with 103 kJ·mol-1 nearly the same as
calculated for CH-MS 1. In comparison to (Sa,Sa,Ra)-1 the
intermediate (Sa,Sa,Ra)-2 is destabilized by 15 kJ·mol-1. The
second transition state from (Sa,Sa,Ra)-2 to (Ra,Ra,Sa)-2 is with
112 kJ·mol-1 the highest maximum on the reaction coordinate and
fits very well to the one calculated by time- and temperature
dependent CD spectroscopy (1136 kJ·mol-1); once more
underpinning the stepwise mechanism). The higher inversion
barrier is best explained by the repulsion of the N and O electron
lone pairs of aza-MS 2 being greater than between the more
delocalized σ-electrons of the isosteric CH-bond in MS 1.
To our delight the racemic aza-MS 2 could be separated by chiral
column chromatography using a Chiralpak IETM column (based on
amylose tris (3,5-dichlorophenylcarbamate)) and n-heptane/i-
PrOH (70:30) as eluent (Figure 4). Circular dichroism UV/vis
spectra of both separated enantiomers are mirror-imaged (Figure
5) showing a Cotton effect that is a bit less pronounced as it was
reported for 1.[21] The g-values of 3.41×10-3 (290 nm), -2.70×10-3
(343 nm) and -2.52×10-3 (360 nm) for 2 are in the same order of
magnitude than the ones found for the pure hydrocarbon CH-MS
1. By TD-DFT (BHandHLYP/6-311-G(d,p) is assumed that the red
graph of the CD-spectrum is of the enantiomer (Sa,Sa,Sa)-2 and
the black one of the opposite enantiomer (Ra,Ra,Ra)-2.[23]
6.4 min
49.9%
10.4 min
50.1%
(Ra,Ra,Ra)
(Sa,Sa,Sa)
10.3 min
(Sa,Sa,Sa)
6.6 min
(Ra,Ra,Ra)
5
6
7
8
9
10
11
12
13
retention time [min]
Figure 4. Analytical chiral HPLC traces (IE column, n-heptane/i-PrOH 70:30
v/v,1 mL min-1of racemic 2 (top) and separated enantiomers (middle and
bottom). The assignment is based on TD-DFT calculations of the corresponding
CD spectra (see Fig. 5).
Figure 6. Comparison of reaction paths and calculated barriers (DFT,B3LYP/6-
311G(d,p)) for the stereochemical bowl-to-bowl inversion. black: aza-MS 2; red:
CH-MS 1.
With enantiopure aza-MS 2 in hand the inversion barrier was
calculated by kinetic measurements of CD spectra at various
temperatures (for details, see Supporting Information). With EA =
1136 kJ·mol-1 the barrier is higher than previously found for the
CH-MS 1 (EA = 1044 kJ·mol-1). The difference of +9 kJ·mol-1 has
a significant effect on the half-life times t1/2 for the interconversion,
shifting from 6.90.4 seconds to 7.70.1 hours at 70 ºC.
In conclusion, a chiral negatively curved nitrogen containing PAH
with the shape of a monkey saddle was synthesized in just two
steps from bromotruxene 3. The isosteric substitution of the CH
unit of the inherent three cyclooctatetraene rings of CH-MS 1 by
nitrogen in aza-MS 2 had the effect of energetically stabilization
of the frontier molecular orbitals by about -0.4 eV; a common trend
reported for isosteric pairs of PAHs/aza-PAHs.[18a] The
3
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10.1002/chem.202002826
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stabilization was reflected by higher oxidation and reduction
potentials, measured by CV. What clearly distinguishes this
negatively curved pair of PAH/ aza-PAH from planar ones is the
intrinsic chirality and thus allowed us to study the effect of isosteric
exchange of CH-units by nitrogen on the inversion barrier for
racemisation. The experimentally determined barrier for the aza-
MS 2 was with EA = 113 kJ·mol-1 about 10 kJ·mol-1 higher than
previously reported for CH-MS 1.[21] This prolongs the half-time
stability e.g. at 70 oC from a few seconds to several hours. This is
very important for the further use of derivatives of aza-MS 2 as
enantiopure chiral reactant towards the synthesis of Mackay-type
cage structures[13] - which is ongoing in our laboratories.
Table 1. Comparison of key-data of monkey saddle PAH 1 and aza monkey saddle PAH 2.
b]
b]
Cmpd
ELUMO,DFT
[eV]
EHOMO,DFT
a]
EIP,CV
[eV]
EEA,CV
[eV]
Egap,CV
[eV]
λmax
[nm]
λonset
[nm]
Egap,opt
[eV]
EA,rac, DFT
[kJ·mol-1]
EA,rac, exp
[kJ·mol-1]
t1/2 @70 oC
[eV]
CH-MS 1
aza-MS 2
-1.90
-2.38
-5.23
-5.65
-5.45
-5.65
-3.0
-3.3
2.5
2.4
280
273
490
520
2.5
2.4
102
112
1044 6
1136
6.90.4 s
7.70.1 h
[a] B3LYP/6-311G(d,p). [b] 1mM in DCM; scan speed: 100 mV s-1; Fc/Fc+ was used as internal reference.[24] ECV = -(Eonset + 5.1 eV).
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Acknowledgements
[5]
The authors are grateful for funding this project (TP-A04) by
Deutsche
Forschungsgemeinschaft
(DFG)
within
the
collaborative research center SFB 1249 on “N-heteropolycycles
as functional materials”. Support by the state of Baden-
Württemberg through bwHPC and the DFG through grant no INST
40/467-1 FUGG (JUSTUS cluster) is acknowledged.
[6]
[7]
[8]
[9]
Keywords: polycyclic aromatic hydrocarbons • azocine • N-
heteroarenes • negative curvature • monkey saddle • chirality
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10.1002/chem.202002826
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Isosteric exchange of CH↔N in a chiral monkey saddle makes the difference, increasing the conformational stability and significantly
reduces the frequency of the bowl-to-bowl-inversion.
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