Design and synthesis of a novel banana-shaped functional molecule via double cross-coupling

Article abstract of DOI:10.3390/molecules24040698

A novel banana-shaped molecule using 2,8-Dimethyl-6H,12H-5,11-methanodibenzo [b,f] [1,5]diazocine (Tr?ger’s base) as bent-core was synthesized via double Carbon-Carbon cross-coupling reaction. The double Sonogashira cross-coupling reaction was optimized by using Pd(PPh₃)₂Cl₂ as catalyst, CuI as cocatalyst and diisopropylamine as base in place of triethylamine. The structure of this compound was confirmed by ¹H-NMR, ¹³C-NMR, Fourier transform infrared (FT-IR) spectroscopy and mass spectrometry.

Full text of DOI:10.3390/molecules24040698

molecules
Article
Design and Synthesis of a Novel Banana-Shaped
Functional Molecule via Double Cross-Coupling
Bingchuan Yang 1,2,3,*, Guodong Shen 1, Xianqiang Huang 1 and Rutao Liu 2,
*
1
School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252000, China;
shenguodong@lcu.edu.cn (G.S.); hxq@lcu.edu.cn (X.H.)
School of Environmental Science and Engineering, Shandong University, Jinan 250100, China
The Department of Chemistry, University of South Florida, 4202 East Fowler Avenue, Tampa, FL 33620, USA
Correspondence: bingchuan@mail.usf.edu (B.Y.); rutaoliu@sdu.edu.cn (R.L.);
Tel.: +1-813-613-5202 (B.Y.); +86-1380-531-5917 (R.L.)
2
3
*
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
Academic Editors: Artur M. S. Silva and Maria Manuel Marques
Received: 4 January 2019; Accepted: 12 February 2019; Published: 15 February 2019
ꢀꢁꢂꢃꢄꢅꢆ
Abstract: A novel banana-shaped molecule using 2,8-Dimethyl-6H,12H-5,11-methanodibenzo [b,f]
[1,5]diazocine (Tröger’s base) as bent-core was synthesized via double Carbon-Carbon cross-coupling
reaction. The double Sonogashira cross-coupling reaction was optimized by using Pd(PPh3)2Cl2 as
catalyst, CuI as cocatalyst and diisopropylamine as base in place of triethylamine. The structure of this
compound was confirmed by 1H-NMR, 13C-NMR, Fourier transform infrared (FT-IR) spectroscopy
and mass spectrometry.
Keywords: bent-core; Tröger’s base; double Sonogashira coupling
1. Introduction
Molecules bearing bent-cores have attracted extensive worldwide attention due to their
outstanding properties. Some of these molecules have potential applications in asymmetric
catalysis [
molecules have rigid
special structure, the molecules can pack closely and align in the direction of bending [
banana-shaped molecules with bent-cores and flexible tails can exhibit a variety of novel characteristics
involving chirality, polarity, and liquid crystalline (LC) features [ 12]. Especially when bent-core
1,
2
], and others have been wildly used in molecular recognition [
shape, which will induce intermolecular polarity. Also because of their
]. As a result,
3–6]. Banana-shaped
Λ
7
8–
is constructed in the liquid crystal molecules, this special bent shape promotes molecules packed in
polar [3] and tilted [13] ways to form chiral lamellar phases such as the B2 and B7 [14–16].
Bent-core liquid crystal molecules also have nonlinear optical properties due to their unique shape
and polar character, which have attracted considerable interest. What is more, polar characters
of bent-shaped molecules were also used to develop ferroelectric switches or anti-ferroelectric
materials [17].
This special usages have drawn great interest from not only scientific researchers but also
industrial designers. Based on these fused properties, liquid crystals have been widely used in
one-dimensional conductors, photoconductors, light emitting diodes, photovoltaic solar cells, and gas
sensors [18–21].
We have been focusing on the development of facile syntheses of heterocyclic systems [22–26]
Herein, we choose bent-shaped 5,6,11,12-tetrahydrodibenzo[b,f] [1,5]diazocines (Tröger’s base like)
as the bent-core to design and synthesize a novel banana-shaped molecule (Scheme 1). Tröger’s
base was first synthesized by Tröger in 1887 [27], and its space structure is just similar to the letter
of the Greek alphabet
and rigid C2 symmetry property [28
Λ
. It has recently received renewed interest due to its inherent chirality
39]. Tröger’s base is a rigid and curved molecule due to
–
Molecules 2019, 24, 698; doi:10.3390/molecules24040698
www.mdpi.com/journal/molecules

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its bridgehead stereogenic nitrogen atoms. A methylene strap connects the two chiral nitrogen
atoms together, which is very suitable for the construction of liquid crystalline materials. To the
different substituted groups, the dihedral angle between two benzene rings in Tröger’s base changes
from 90◦ to 100◦. For example, the dihedral angle between two aromatic rings in (5S,11S)-2,8-
dibromo-6H,12H-5,11-ethanodibenzo[b,f] [1,5]diazocine is 94.5◦ [40], and the dihedral angle between
two aromatic rings 1,2,3,4,7,8,9,10-octafluoro-6H,12H-5,11-methanodibenzo[b,f][1,5]-diazocine is
98.4◦ [41].
Scheme 1. Retrosynthetic Analysis of target molecule A.
Tröger’s base has been constructed as a bent-core to bind different functional groups without
ruining their original properties. And Tröger’s base can be used as molecular clefts because the
bicyclic skeleton forces the molecule in a rigid locked conformation with the benzene rings in
proximity. In supramolecular chemistry, Tröger’s base has been explored for the recognition of aliphatic
dicarboxylic acids and enzyme inhibitors [42
Tröger’s base was also used in DNA intercalation and acted as ligands in asymmetric synthesis [48].
What is more, this -shaped twisted configuration is theoretically disadvantageous for the formation
of close stacking, which may lead to fluorescence quenching in the solid state. But recent study
revealed that the -shaped Tröger’s base scaffolds can express aggregation-induced emission (AIE)
properties [49,50].
–45]. Enantiomerically enriched [46,47] analogues of
Λ
π–π
Λ
2. Experimental Section
2.1. General
All chemicals purchased were used without purification. THF of analytical grade and de-ionized
1
water were used throughout the experiment as solvents. H-NMR spectra were recorded on a Bruker
Advance 400 (400 MHz) or 300 (300 MHz) spectrometer, using CDCl3 as solvent and tetramethylsilane
(TMS) as internal standard. 13C-NMR spectra were recorded on a Bruker Advance 100 (100 MHz) or
75 (75 MHz) spectrometer, using CDCl3 as solvent and tetramethylsilane (TMS) as internal standard.
HRMS spectra were determined on a Q-TOF6510 spectrograph (Agilent). Supplementary Materials:
Representative experimental procedures, spectral data of compounds 3–8. This material is available
free of charge via the internet.
2.2. Experimental Procedure for the Preparation of
2,8-Dibromo-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine (2)
To a stirred mixture of the 4-bromoaniline (1) (3.44 g, 30 mmol), paraformaldehyde (5.40 g,
60 mmol) was added with TFA (100 mL; 1.3 mol), the mixture was stirred for 168 h at room temperature
Then, TFA was removed in vacuo, water (100 mL) was added followed by the addition of saturated
aqueous NH3 solution (100 mL). The aqueous layer was extracted with dichloromethane (3
The combined organic layers were dried (MgSO4), filtered, concentrated in vacuo and purified by
×
50 mL).

Molecules 2019, 24, 698
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flash chromatography on silica gel to gain the product
2
(PE:EtOAc = 20:1, 3.363 g, 88%). As shown in
1
Figure 1. H-NMR (DMSO, TMS, 400 MHz): 4.08 (d, J = 16.8 Hz, 1H), 4.2 (s, 1H), 4.62 (d, J = 16.8 Hz,
1H), 6.87 (d, J = 8.48 Hz, 1H), 7.23 (d, J = 8.08 Hz, 1H), 7.46 (d, J = 8.56 Hz, 1H). 13C-NMR (CDCl3, TMS,
100 MHz): 58.3, 66.7, 116.8, 126.7, 129.7, 129.7, 130.6, 146.8.
Figure 1. Ball-and-Stick model of compound 8.
2.3. Experimental Procedure for the Preparation of
2,8-Bis((trimethylsilyl)ethynyl)-6,12-dihydro-5,11-methanodiben-zo[b,f][1,5]diazocine (3)
A Schlenk tube containing 2,8-dibromo-6,12-dihydro-5,11-methanodibenzo [b,f][1,5] diazocine (2)
(0.38 g, 1 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.07 g, 0.1 mmol), copper(I) iodide
(0.012 g, 0.06 mmol), triphenylphosphine (0.052 g, 0.2 mmol) was degassed on a vacuum line by
repeatedly alternating between an argon atmosphere and vacuum. Then diisopropylamine (30 mL)
was added dropwisely. Finally, a solution of trimethylsilylacetylene (0.53 mL, 3 mmol) was added
dropwise and the mixture was stirred at 50 ◦C for 11 h. After that the mixture was filtered through a
pad of celite and dichloromethane (30 mL) was used to wash the additional product through the celite
pad. The filtrate was evaporated to dryness and purified by flash chromatography on silica gel to gain
1
the product
3
(PE:EtOAc = 6:1, 0.250 g, 60%).As shown in Figure 2. H-NMR (CDCl3, 300 MHz)
δ
0.20
(s, 18H), 4.10 (d, J =16.8 Hz, 2H), 4.27 (s, 2H), 4.62 (d, J =16.8 Hz, 2H), 7.01 (d, J = 8.4 Hz, 4H), 7.24 (dd,
J = 8.7, 2.4 Hz, 2H). 13C-NMR (CDCl3, TMS, 100 MHz): 0.00, 58.5, 66.8, 93.4, 104.8, 118.6, 124.8, 127.7,
130.7, 131.0, 148.3.
Figure 2. The optimized structure of 8 calculated by Gaussian 09 program using the B3LYP method
with the 6-31G + (d,p) basis set [51].
2.4. Experimental Procedure for the Preparation of
2,8-Diethynyl-6,12-dihydro-5,11-methanodibenzo[b,f][1,5]diazoci-ne (4)
2,8-bis((trimethylsilyl)ethynyl)-6,12-dihydro-5,11-methanodi- benzo[b,f][1,5] diazocine (0.150 g,
0.362 mmol) was dissolved in THF/MeOH (VTHF:VMeOH = 1:1) 50 mL and potassium carbonate was
added (0.333 g, 2.461 mmol). The mixture was stirred for 5 h, filtered, concentrated in vacuo and
purified by flash chromatography on silica gel to gain the product 4 (PE:EtOAc = 6:1, 0.092 g, 95%). As
1
shown in Figure 3. H-NMR (CDCl3, 300 MHz)
δ 2.97 (s, 2H), 4.13 (d, J = 16.8 Hz, 2H), 4.29 (s, 2H),

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4.65 (d, J = 16.8 Hz, 2H), 7.07 (d, J = 8.1 Hz, 4H), 7.24 (dd, J = 8.1 Hz, 1.5 Hz, 2H); 13C-NMR (CDCl3,
300 MHz) δ 58.4, 66.7, 76.5, 76.6, 77.0, 77.5, 83.3, 117.6, 125.0, 127.8, 130.9, 131.2, 148.5.
-1.491905 eV
LUMO
ΔE = 5.718146 eV
HOMO
-7.210052 eV
Figure 3. HOMO/LUMO imagines of 8 calculated by Gaussian 09 program using the B3LYP method
with the 6-31G + (d,p) basis set [51].
2.5. Experimental Procedure for the Preparation of 4-(Methoxycarbonyl)phenyl-4-iodobenzoate (7)
One equivalent of p-Iodobenzoic acid ( ) (0.250 g, 1 mmol), methyl 4-hydroxybenzoate (6) (0.152 g,
5
1 mmol), DCC (0.206 g, 1 mmol) and DMAP (0.025 g, 0.2 mmol) were dissolved in dimethyl carbonate
(DMC) 30 mL and stirred at room temperature for 10 h. The whole mixture was filtered and the filtrate
was distilled by vacuum. The crude product was purified by flash chromatography on silica gel to
1
gain the product 7 (PE:EtOAc = 6:1, 0.308 g, 80%). H-NMR (CDCl3, 400 MHz)
δ 3.93 (s, 6H), 4.73
(d, J = 16.8 Hz, 2H), 7.29 (d, J = 8.7 Hz, 2H), 7.89 (s, 4H), 8.12 (d, J = 8.7 Hz, 2H); 13C-NMR (CDCl3,
400 MHz) δ 52.2, 102.0, 121.7, 128.0, 128.6, 131.3, 131.6, 138.1, 154.4, 164.2, 166.3.
2.6. Experimental Procedure for the Preparation of
Bis(4-(methoxycarbonyl)phenyl)4,40-((6,12-dihydro-5,11-methano-dibenzo[b,f][1,5]diazocine-2,8-diyl)bis
(ethyne-2,1-diyl))diben-zoate (8)
A Schlenk tube containing 2,8-diethynyl-6,12-dihydro-5,11-methanodibenzo[b,f][1,5]diazocine
(97 mg, 0.36 mmol), 4-(methoxycarbonyl)phenyl 4-iodobenzoate (276 mg, 0.72 mmol),
dichlorobis(triphenylphosphine)palladium(II) (25 mg, 0.036 mmol), copper(I) iodide (3 mg,
0.018 mmol), triphenylphosphine (19 mg, 0.072 mmol) and dry triethylamine (20 mL) was degassed
on a vacuum line by repeatedly alternating between an argon atmosphere and vacuum. The reaction
◦
mixture was stirred at 50 C for 18 h. The reaction mixture was then filtered and evaporated to dryness.
The product was purified by column chromatography on silica gel using CHCl3:EtOAc = 15:1 as the
◦
eluent to gain the product 8 (141 mg, 50%). white solid; m.p. 210 C. IR (KBr),
2202, 1733, 1713, 1600, 1506. H-NMR (CDCl3, 400 MHz)
ν
(cm−1): 2946, 2900,
max
1
δ 3.93 (s, 6H), 4.22 (d, J = 16.8 Hz, 2H), 4.35 (s,
2H), 4.73 (d, J = 16.8 Hz, 2H), 7.15 (d, J = 9.8 Hz, 4H), 7.30 (d, J = 8.1 Hz, 2H), 7.39 (dd, J = 8.3, 1.7 Hz,
2H), 7.60 (d, J = 8.5 Hz, 4H), 8.14 (t, J = 9.8 Hz, 14.1 Hz, 8H); 13C-NMR (CDCl3, 400 MHz)
δ
52.2, 58.5,
66.8, 88.0, 92.9, 118.0, 121.7, 125.2, 127.9, 128.0, 128.2, 129.1, 130.2, 130.6, 131.0, 131.3, 131.6, 148.8, 154.5,
164.1, 166.3; HRMS (EI): Calcd for C49H34N2O8, 779.2388; found, 779.2383.
2.7. Theoretical Study
Computational methods. All calculations were conducted using the B3LYP functional (Gaussian
09, Revision B. 01.; Gaussian, Inc.: Wallingford, 2009) combined with the 6-31+(d,p) basis set,
as implemented in Gaussian 09 software package (Gaussian 09, Revision B. 01.; Gaussian, Inc.:
Wallingford, 2009). Vibrational analyses at the same level of theory were also carried out to confirm all

Molecules 2019, 24, 698
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stationary points as minima (zero imaginary frequencies) or first-order saddle points (one imaginary
frequency) and to provide free energies at 298.15 K.
3. Results and Discussion
As shown in Scheme 2, starting from 4-bromoaniline
by condensation of with paraformaldehyde in trifluoroacetic acid (TFA) according to the procedure
described in Scheme 1. Tröger’s base derivative could react with trimethylsilylacetylene (TMSA)
smoothly to get high yield product under the common conditions of Sonogashira cross-coupling
reaction by using Pd(PPh3)2Cl2 as catalyst, CuI as cocatalyst and diisopropylamine as base in place of
triethylamine. Then the trimethylsilyl groups of was removed to obtain the product in excellent
yield under the conditions of K2CO3 as the base and VTHF:VMeOH = 1:1 as solvent. Intermediate
1, rac-(
±
)-Tröger’s base 2 was synthesized
1
2
3
3
4
7
was obtained from p-iodobenzoic acid and Methyl 4-hydroxybenzoate under the conditions of
0
N,N -dicyclohexylcarbodiimide (DCC) as dehydrant and 4-dimethylaminopyridine (DMAP) as catalyst
in the solvent of dimethyl carbonate (DMC). At the end, the intermediate
target molecule 14] in high yield under the conditions of PdCl2(PPh3)2 and CuI as cocatalyst and
triethylamine as base.
7 could react with 3, to obtain
8
[
Scheme 2. Synthesis of Tröger’s base like derivative.
We slightly modified the Sonogashira cross-coupling reaction conditions by using
diisopropylamine as base instead of triethylamine, and the reaction temperature changed from
room temperature to 50 ◦C improving the yield of 2,8-dibromo-6,12-dihydro-5,11-methano-
dibenzo[b,f][1,5]diazocine
6
to 60% successfully. Finally, the target molecule was obtained in 26%
overall yield in five steps.
To understand the structure changes of
8. We carried out density functional theory (DFT)
calculation by Gaussian 09 program using the B3LYP method with the 6-31G + (d,p) basis set.
The optimized structure shown in Figures 1 and 2 has a clear bent-core configuration, however
the tails of the molecule are not flexible enough. The HOMO-LUMO energy gap of compound
8 is
5.718146 eV (Figure 3). Electron cloud transferred from the Tröger’s base like core to the benzene rings
when the molecule excitated from HOMO to LUMO. According to the research results, this molecule
has potential application in liquid crystal field and further study will be conducted.

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4. Conclusions
In summary, we have designed and synthesized a novel banana-shaped molecule based on
Tröger’s base via double Sonogashira cross-coupling reaction. The chemical structures have been
1
characterized by H-NMR, 13C-NMR, Fourier transform infrared (FT-IR) spectroscopy and mass
spectrometry. Theoretical study was also conducted by Gaussian 09 program, and we confirmed that
the molecule has a bent-core structure. In the future, we will use this method to obtain a series of these
bent-core compounds. Further studies on its applications in the photology are currently in progress.
Supplementary Materials: Representative experimental procedures, spectral data of compounds 3–8. This
material is available free of charge via the internet.
Author Contributions: Investigation, B.Y.; Methodology, B.Y.; Project administration, X.H.; Supervision, R.L.;
Writing-original draft, G.S.
Funding: We are grateful to National Science Foundation of China (No. 51378306, 21402079) and Liaocheng
University fund (318051515, 201610447013) for financial support of this research.
Conflicts of Interest: The authors declare no conflicts of interest.
Date Availability: The data used to support the findings of this study are available from the corresponding author
upon request.
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Sample Availability: Samples of the compounds 3–8 are available from the authors.
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