Design and Synthesis of a Novel Banana-Shaped Functional Molecule via Double Cross-Coupling

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.


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 [1,2], and others have been wildly used in molecular recognition [3][4][5][6]. Banana-shaped molecules have rigid Λ shape, which will induce intermolecular polarity. Also because of their special structure, the molecules can pack closely and align in the direction of bending [7]. As a result, banana-shaped molecules with bent-cores and flexible tails can exhibit a variety of novel characteristics involving chirality, polarity, and liquid crystalline (LC) features [8][9][10][11][12]. Especially when bent-core 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][15][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][19][20][21].

General
All chemicals purchased were used without purification. THF of analytical grade and de-ionized water were used throughout the experiment as solvents. 1 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. 13 C-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. 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][43][44][45]. Enantiomerically enriched [46,47] analogues of Tröger's base was also used in DNA intercalation and acted as ligands in asymmetric synthesis [48]. What is more, this Λ-shaped twisted configuration is theoretically disadvantageous for the formation of π-π close stacking, which may lead to fluorescence quenching in the solid state. But recent study revealed that the Λ-shaped Tröger's base scaffolds can express aggregation-induced emission (AIE) properties [49,50].

General
All chemicals purchased were used without purification. THF of analytical grade and de-ionized water were used throughout the experiment as solvents. 1 H-NMR spectra were recorded on a Bruker Advance 400 (400 MHz) or 300 (300 MHz) spectrometer, using CDCl 3 as solvent and tetramethylsilane (TMS) as internal standard. 13 C-NMR spectra were recorded on a Bruker Advance 100 (100 MHz) or 75 (75 MHz) spectrometer, using CDCl 3 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.

Experimental Procedure for the Preparation of
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 NH 3 solution (100 mL). The aqueous layer was extracted with dichloromethane (3 × 50 mL). The combined organic layers were dried (MgSO 4 ), filtered, concentrated in vacuo and purified by flash chromatography on silica gel to gain the product 2 (PE:EtOAc = 20:1, 3.363 g, 88%). As shown in Figure 1. 1  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 × 50 mL). The combined organic layers were dried (MgSO4), filtered, concentrated in vacuo and purified by flash chromatography on silica gel to gain the product 2 (PE:EtOAc = 20:1, 3.363g, 88%). As shown in Figure 1. 1

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 stationary points as minima (zero imaginary frequencies) or first-order saddle points (one imaginary frequency) and to provide free energies at 298.15 K.

Results and Discussion
As shown in Scheme 2, starting from 4-bromoaniline 1, rac-(±)-Tröger's base 2 was synthesized by condensation of 1 with paraformaldehyde in trifluoroacetic acid (TFA) according to the procedure described in Scheme 1. Tröger's base derivative 2 could react with trimethylsilylacetylene (TMSA) smoothly to get high yield product 3 under the common conditions of Sonogashira cross-coupling reaction by using Pd(PPh 3 ) 2 Cl 2 as catalyst, CuI as cocatalyst and diisopropylamine as base in place of triethylamine. Then the trimethylsilyl groups of 3 was removed to obtain the product 4 in excellent yield under the conditions of K 2 CO 3 as the base and V THF :V MeOH = 1:1 as solvent. 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 Figure 1 and Figure 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. 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-methanodibenzo[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.

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 characterized by 1 H-NMR, 13 C-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.