Chinese Chemical Letters  2015, Vol.26 Issue (07):885-888   PDF    
A switchable bistable [2]rotaxane based on phosphine oxide functional group
Shuang-Jin Zhanga, Qi Wangb, Ming Chengb, Xiao-Hong Qiana, Yang Yanga , Ju-Li Jiangb , Le-Yong Wangb    
a School of Petrochemical Engineering, Changzhou University, Changzhou 213164, China;
b Key Laboratory of Mesoscopic Chemistry of MOE, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China
Abstract: A switchable bistable rotaxane based phosphine oxide functional group-containingmacrocycle has been constructed successfully, in which the macrocycle can be easily switched between dibenzylammonium and triazole recognition sites by using the simple base/acid stimuli.
Key words: Rotaxane     Molecular shuttle     Phosphine oxide functional group     Macrocycle    
1. Introduction

Mechanically interlocked molecules (MIMs) [1],in particular rotaxanes and catenanes,have grown to an unprecedented level in the past few decades,not only for their intriguing architectures and topologies but also for their potential applications in molecular machines [2]. Among these artificial molecular systems,rotaxane based molecular shuttles,in which the ring component can be switched between different,well-separated recognition sites on the dumbbell-shaped component in response to external stimuli, have attracted much attention and shown potential applicability in molecular switches and machines because of their adjustable physical and chemical properties [3].

In 2011,Li and co-workers synthesized a multistable molecular rotaxane with three successive movement processes driven by acid/base stimuli,which are all accompanied with fluorescent responses [4]. In 2012,a switchable three-station [2]rotaxane was developed by Chiu's group,where the macrocycle can be easily switched between different binding sites by addition of acid/base, metal ions or anions [5]. In 2013,Liu and co-workers constructed a switchable double-leg molecular elevator containing one acceptor and one donor on its top and bottom,in which the reversible elevator movement could be controlled upon the addition of base and acid [6]. As shown above,the shuttling motion of the macrocycle between different recognition sites driving by base/ acid responsiveness played an important role in the fabrication of functional molecular machines.

Phosphine oxide functional group is an important unit in coordination chemistry and organometallic catalysis [7],which has been widely employed for constructing interlocked structures due to its good hydrogen bonding acceptor properties [8]. Recently,our group has developed a switchable three-station molecular shuttle using phosphine oxide as a recognition site where the macrocycle can be selectively and readily shuttled between these three different binding stations by addition of base/acid or by addition/ removal of acetate anions [8c]. Herein,we report a novel macrocycle bearing phosphine oxide functional group would afford potential binding sites for guests due to its unique property as an excellent hydrogen bonding acceptor. On the basis of the macrocycle,we design and construct a switchable bistable molecular shuttle containing two well-separated recognition sites, namely dibenzylammonium (DBA+) and triazole stations in the dumbbell-shaped molecule,in which the shuttling motion of the macrocycle between two different states can be obtained by using base/acid stimuli (Scheme 1).

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Scheme 1.The shuttling motion of the macrocycle along the rotaxane thread.
2. Experimental

All reactions were performed in atmosphere unless noted. The commercially available reagents and solvents were either employed as purchased or dried according to procedures described in the literature. Compounds 5 [9],7 [10],8 [11],9 [12],and 10 [13] were prepared by preciously published literature procedures. NMR spectra were recorded on a Bruker DPX 300 MHz or 400 MHz spectrometer and the chemical shifts (δ) were expressed in ppm and J values were given in Hz. Low-resolution electrospray ionization mass spectra (LR-ESI-MS) were obtained on Finnigan MatTSQ 7000 instruments.

Preparation of [1-H][PF6] (Scheme 2): A mixture of 3 (0.29 g, 0.48 mmol),4 (0.26 g,0.48 mmol),and [Cu(MeCN)4]PF6 (0.27 g, 0.72 mmol) was stirred in dry CH2Cl2 (70 mL) at room temperature under argon for 2 h. A solution of stopper compound 5 (0.33 g, 0.96 mmol) in dry CH2Cl2 (20 mL) was added and stirred for another 48 h under argon. The solvent was removed after filtration, and the crude product was subjected to silica-gel column chromatography (CH2Cl2/MeOH,200:1,v/v) to afford desired [2]rotaxane [1-H][PF6] as a white solid (0.12 g,17%). Mp 88-90℃. 1H NMR (400 MHz,CD3CN,298 K) δ: 8.46 (s,2H),7.75 (s,1H),7.52- 7.29 (m,27H),7.01 (t,2H,J = 7.9 Hz),6.97 (d,2H,J = 8.7 Hz),6.61- 6.58 (m,2H),6.57-6.55 (m,2H),6.50 (br s,1H),6.49-6.48 (m,3H), 6.42-6.41 (m,2H),6.26 (d,2H,J = 2.2 Hz),5.36 (s,2H),5.11 (s, 2H),5.02 (s,4H),4.93 (s,4H),4.37-4.31 (m,4H),3.86-3.76 (m,2H), 3.76-3.61 (m,6H),3.55-3.44 (m,12H),3.40-3.55 (m,2H), 3.24-3.18 (m,2H); 13C NMR (100 MHz,CD3CN,298 K): δ 160.8, 160.6,159.6,158.1 (d,J = 2.7 Hz),138.5,137.5,137.4,135.3,133.5 (d,J = 8.8 Hz),132.9,132.7 (d,J = 2.3 Hz),131.1 (d,J = 9.3 Hz),130.5 (d,J = 2.0 Hz),130.2,129.2,129.1 (d,J = 2.2 Hz),128.6 (d, J = 2.6 Hz),128.3,128.0,124.6,123.0 (d,J = 5.9 Hz),116.8 (d, J = 3.9 Hz),115.5,113.5 (d,J = 2.6 Hz),110.5,107.7,102.3,101.8, 72.0,71.6,71.1,70.4,70.3,68.5,65.8,61.9,54.0,52.2,51.8,36.5 (d, J = 62.3 Hz); 31P NMR (160 MHz,CD3CN): δ 37.05 (s); LR-ESI-MS: m/z calcd. for [M-PF6]+ C82H86N4O12P+,1349.60,found 1349.40 (Fig. 1).

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Fig. 1.LR-ESI-MS spectrum of [1-H][PF6].

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Scheme 2.Synthesis of the molecular shuttle [1-H][PF6].

Preparation of 6 (Scheme 3) [14]: A solution of 8 (1.90 g, 5.97 mmol) and 7 (1.36 g,8.45 mmol) in dry MeOH (120 mL) was heated under reflux until completion of the aldehyde (monitored by 1H NMR). The reaction mixture was then cooled to 0℃,and then NaBH4 (2.26 g,59.7 mmol) was added in several portions cautiously. The resulting solution was warmed to room temperature gradually and then stirred overnight before being concentrated under reduced pressure. The residue was dissolved in CH2Cl2(150 mL),washed with H2O (2 × 50 mL) and brine (50 mL),the organic phase was dried over anhydrous Na2SO4 and filtered. The solvent was then removed to provide a yellow viscous oil,which was purified by silica-gel column chromatography (CH2Cl2/CH3OH, 100:1,v/v) to afford 6 as a colorless viscous oil (2.30 g,83%). 1H NMR (300 MHz,CDCl3,298 K): δ 7.46-7.29 (m,10H),7.25 (d,2H, J = 8.7 Hz),6.93 (d,2H,J = 8.7 Hz),6.61 (d,2H,J = 2.2 Hz),6.52 (t, 1H,J = 2.2 Hz),5.03 (s,4H),4.68 (d,2H,J = 2.4 Hz),3.73 (s,2H),3.72 (s,2H),2.51 (t,1H,J = 2.4 Hz); 13C NMR (75 MHz,CDCl3,298 K): δ 160.2,156.7,143.1,137.1,133.5,129.5,128.7,128.1,127.7,114.9, 107.3,100.8,78.9,75.7,70.1,55.9,53.2,52.5; LR-ESI-MS: m/z calcd. for [M+H]+ C31H30NO3+,464.22,found 464.20.

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Scheme 3.Synthesis of the dumbbell-shaped thread [2-H][PF6].

Preparation of 3 (Scheme 3) [14]: A solution of 6 (2.30 g, 4.96 mmol) in CH3OH (40 mL) was stirred at room temperature. Concentrated HCl was added to the previous solution dropwise in order to adjust pH < 2,and the resulting solution was stirred for 1 h. After removal of the solvent,the residue was suspended in acetone (40 mL),followed by addition of excess NH4PF6 (2.53 g, 15.5 mmol) aqueous solution,and the mixture was stirred for 4 h at room temperature. The reaction mixture was then concentrated under reduced pressure. The residue was diluted with purified water (100 mL) and extracted with CH2Cl2 (2 × 150 mL). The organic layers were combined,dried over anhydrous Na2SO4,and concentrated to obtain the target 3 (2.77 g,92%) as a white solid. Mp: 109-111℃. 1H NMR (400 MHz,CDCl3,298 K): δ 7.40-7.35 (m,10H),7.22 (d,2H,J = 8.7 Hz),6.91 (d,2H,J = 8.7 Hz),6.62-6.61 (m,1H),6.59 (d,2H,J = 2.0 Hz),5.01 (s,4H),4.57 (d,2H,J = 2.4 Hz), 3.95 (s,2H),3.94 (s,2H),2.48 (t,1H,J = 2.4 Hz); 13C NMR (75 MHz, CDCl3,298 K): δ 160.6,158.6,136.5,132.0,131.4,128.6,128.1, 127.6,122.7,115.6,108.5,104.1,78.1,76.1,70.1,55.7,51.3,50.7; LR-ESI-MS: m/z calcd. for [M-PF6]+ C31H30NO3+,464.22,found 464.20.

Preparation of [2-H][PF6] (Scheme 3): A mixture of 3 (0.21 g, 0.34 mmol),[Cu(MeCN)4]PF6 (0.18 g,0.48 mmol) and 5 (0.23 g, 0.67 mmol) was stirred in dry CH2Cl2 (50 mL) at room temperature under nitrogen for 24 h. After filtration,the filtrate was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography (CH2Cl2/CH3OH,100:1,v/v) to give desired [2-H][PF6] as a white solid (0.20 g,64%). Mp 73-75℃. 1H NMR (400 MHz,CD3CN,298 K): δ 7.83 (s,1H),7.44-7.32 (m, 22H),7.04 (d,2H,J = 7.6 Hz),6.66 (brs,2H),6.64 (brs,1H),6.57 (t, 1H,J = 2.1 Hz),6.51 (d,2H,J = 2.1 Hz),5.45 (s,2H),5.15 (s,2H),5.07 (s,4H),5.02 (s,4H),3.98 (brs,4H); 13C NMR (75 MHz,CD3CN, 298 K): δ 160.3,158.7,143.6,138.0,137.0,136.1,131.1,129.6, 128.6,128.0,127.8,126.0,124.1,115.0,108.4,107.2,102.1,101.7, 69.8,61.4,53.5,51.4,51.2; LR-ESI-MS: m/z calcd. for [M-PF6]+ C52H49N4O5+,809.37,found 809.40.

Preparation of 4 (Scheme 4): A high dilute mixture of 9 (0.50 g, 1.48 mmol),K2CO3 (2.04 g,14.8 mmol) and n-Bu4NI (0.04 g, 0.11 mmol) was stirred in dry CH3CN (350 mL) at 80℃ under argon,then a dilute solution of compound 10 (0.81 g,1.48 mmol) in dry CH3CN (60 mL) was added to the solution very slowly and stirredforanother3daysunderargon.Afterremovalofthesolvent, the residue was dissolved in CH2Cl2 (150 mL),washed with H2O (2 × 50 mL),the organic phase was dried over anhydrous Na2SO4 and filtered. The solvent was removed under reduced pressure,and then the crude product was purified by silica-gel column chromatography (CH2Cl2/MeOH,50:1,v/v) to afford 4 as a white solid (0.45 g,56%). Mp 46-49℃. 1H NMR (400 MHz,CD3CN, 298 K): δ 7.68-7.66 (m,2H),7.54-7.45 (m,3H),7.08 (t,2H, J = 7.9 Hz),6.85 (m,2H),6.73 (d,2H,J = 8.2 Hz),6.61 (d,2H, J = 7.4 Hz),4.05 (t,4H,J = 4.7 Hz),3.76-3.73 (m,4H),3.63-3.61 (m, 12H),3.31 (d,4H,2J(H,P) = 13.0 Hz); 13C NMR (75 MHz,CD3CN, 298 K): δ 159.1 (d,J = 2.5 Hz),134.5 (d,J = 8.0 Hz),133.5,132.6, 132.3 (d,J = 2.7 Hz),131.5 (d,J = 8.8 Hz),129.8 (d,J = 2.3 Hz),129.0 (d,J = 11.3 Hz),122.9 (d,J = 5.5 Hz),117.0 (d,J = 4.9 Hz),113.3 (d, J = 2.7 Hz),71.0,70.9 (d,J = 4.7 Hz),69.7,67.8,37.4 (d,J = 63.3 Hz); 31P NMR (160 MHz,CD3CN): δ 33.23 (s); LR-ESI-MS: m/z calcd. for [M+H]+ C30H38O7P+,541.59,found541.25;[M+NH4]+ C30H41NO7P+, 558.26,found 558.25.

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Scheme 4.Synthesis of the macrocycle 4.
3. Results and discussion

Compound 3 was synthesized from 7 and 8 as starting materials in good yield similar to the reported procedure [14]. Compound 4 was synthesized in one step from 9 and 10 in 56% yield using the pseudo-high-dilution technique. The novel macrocycle 4 bearing phosphine oxide functional group would afford potential binding sites for guests. And then,based on the recognition motif between 3 and 4,the novel [2]rotaxane was obtained in 17% yield by employing "threading-followed-by-stoppering" protocol,and the widely used CuAAC "click" reaction was used to introduce the stoppers owing to the mild condition and high efficiency of the "click" reaction [15].

The structure of molecular shuttle [1-H][PF6] was confirmed through the comparison of the 1H NMR spectra of [1-H][PF6], dumbbell-shaped thread [2-H][PF6],and the phosphine oxidecontaining macrocycle 4. As shown in Fig. 2,peaks corresponding to protons He,Hf of the macrocycle in rotaxane shifted upfield (ΔHe = -0.06 and ΔHf = -0.44,respectively) compared with those of free macrocycle 4. Moreover,the signals of protons Ha and Ha' adjacent to the DBA+ site in [1-H][PF6] moved downfield remarkably (ΔHa ≈ ΔHa' = 0.36) and separated into multiplet, which indicated the threading of the DBA+ group into the macrocycle,while peaks for triazole proton Hc and protons Hb and Hd neighboring the triazole unit in rotaxane shifted upfield slightly (ΔHc = -0.08,ΔHb = -0.04,and ΔHd = -0.09) with respect to the free dumbbell [2-H][PF6]. The result showed that the triazole unit could be another potential binding site for the macrocycle 4,and the ring shuttled between DBA+ station and triazole unit,with the vast majority of its time spent around the DBA+ site [16].

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Fig. 2.Partial 1H NMR spectra (400 MHz, CD3CN, 298 K) of (a) macrocycle 4, (b) molecular shuttle [1-H][PF6], and (c) dumbbell-shaped thread [2-H][PF6].

Subsequently,the base/acid controlled shuttling motion of the macrocycle in molecular shuttle [1-H][PF6] between the DBA+ and triazole stations was investigated by 1H NMR (Fig. 3). Upon addition of 2 equiv. of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to the CD3CN solution of rotaxane [1-H][PF6],the obvious changes were found in the 1H NMR spectra as the DBA+ moiety deprotonated. The protons Ha and Ha' adjacent to the DBA+ station moved upfield significantly (ΔHa = Ha' = -0.72) because of the deprotonation and the movement of the macrocycle; the evident downfield shifts of the triazole proton Hc and protons Hb and Hd adjacent to the triazole unit (ΔHc = 0.93,ΔHb = 0.23,and ΔHd = 0.22) were detected,indicating the complexation occurred between the macrocycle 4 and the triazole station. All of the above evidence confirmed that the macrocycle had moved to the triazole station from the original DBA+ station. Furthermore,upon addition of 4 equiv. of trifluoroacetic acid (TFA) to the sample treated by the base,the [2]rotaxane with the macrocycle at the DBA+ station was reformed again,and a similar spectrum to that of the original molecular shuttle [1-H][PF6] was obtained. The above results demonstrate clearly that the reversible switching of the molecular shuttle [1-H][PF6] can be easily realized by base/ acid control.

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Fig. 3.Partial 1H NMR spectra (400 MHz, CD3CN, 298 K) of [1-H][PF6] (a) the original spectrum, (b) after addition of 2.0 equiv. DBU, and (c) further addition of 4.0 equiv. of TFA.
4. Conclusion

In conclusion,we synthesize successfully a novel macrocycle containing phosphine oxide functional group,and more importantly,a base/acid responsive bistable rotaxane-type molecular shuttle based on this macrocycle was constructed successfully. The shuttling motion process of the macrocycle between the DBA+ site and the triazole site in the dumbbell-shaped molecule can be achieved via de/reprotonation easily. We will try to fabricate the novel supramolecular catalyst based on the switchable bistable [2]rotaxane,in which the DBA+ and triazole stations could be expected to be used as the catalytic sites.

Acknowledgment

We gratefully thank the financial support of the National Natural Science Foundation of China (Nos. 21472088 and 91227106).

References
[1] (a) B. Champin, P. Mobian, J.P. Sauvage, Transition metal complexes as molecular machine prototypes, Chem. Soc. Rev. 36 (2007) 358–366; (b) W. Zhou, S. Zhang, G. Li, et al., Fluorescent alteration on a bistable molecular shuttle, Chem. Phys. Chem. 10 (2009) 2066–2072; (c) X. Ma, H. Tian, Bright functional rotaxanes, Chem. Soc. Rev. 39 (2010) 70–80; (d) S.Y. Dong, J.Y. Yuan, F.H. Huang, A pillar[5]arene/imidazolium [2]rotaxane: solvent-and thermo-driven molecular motions and supramolecular gel formation, Chem. Sci. 5 (2014) 247–252; (e) M. Liu, S. Li, M. Hu, F. Wang, F. Huang, Selectivity algorithm for the formation of two cryptand/paraquat catenanes, Org. Lett. 12 (2010) 760–763; (f) P. Wei, X. Yan, J. Li, et al., Novel [2]rotaxanes based on the recognition of pillar[5]arenes to an alkane functionalized with triazole moieties, Tetrahedron 68 (2012) 9179–9185; (g) M. Xue, Y. Yang, X. Chi, X. Yan, F. Huang, Development of pseudorotaxanes and rotaxanes: from synthesis to stimuli-responsive motions to applications, Chem. Rev. (2015), http://dx.doi.org/10.1021/cr5005869.
[2] (a) D.H. Qu, H. Tian, Novel and efficient templates for assembly of rotaxanes and catenanes, Chem. Sci. 2 (2011) 1011–1015; (b) Z. Zhang, C. Han, G. Yu, F. Huang, A solvent-driven molecular spring, Chem. Sci. 3 (2012) 3026–3031; (c) X. Han, F. Hu, H. Ge, S. Liu, J. Yin, The application of templated-directed directed clipping approach in constructing mechanically interlocked molecules based on N-hetero hetero crown ethers, Prog. Chem. 6 (2015), http://dx.doi.org/ 10.7536/PC150129.
[3] (a) K.D. Zhang, X. Zhao, G.T. Wang, et al., Foldamer-tuned switching kinetics and metastability of [2]rotaxanes, Angew. Chem. Int. Ed. 50 (2011) 9866–9870; (b) Z. Meng, J.F. Xiang, C.F. Chen, Tristable [n]rotaxanes: from molecular shuttle to molecular cable car, Chem. Sci. 5 (2014) 1520–1525; (c) H. Wang, Z.J. Zhang, H.Y. Zhang, Y. Liu, Synthesis of a bistable [3]rotaxane and its pH-controlled intramolecular charge-transfer behavior, Chin. Chem. Lett. 24 (2013) 563–567; (d) Z. Yang, X. Liu, S. Zhao, J. He, Chemically driven [2]rotaxane molecular shuttles, Prog. Chem. 26 (2014) 1899–1913; (e) L.H. Wang, Z.J. Zhang, H.Y. Zhang, H.L. Wu, Y. Liu, A twin-axial[5]pseudorotaxane based on cucurbit[8]uril and a-cyclodextrin, Chin. Chem. Lett. 24 (2013) 949–952.
[4] Y. Zhao, Y. Li, S.W. Lai, et al., Construction of a functional [2]rotaxane with multilevel fluorescence responses, Org. Biomol. Chem. 9 (2011) 7500–7503.
[5] Y.C. You, M.C. Tzeng, C.C. Lai, S.H. Chiu, Using oppositely charged ions to operate a three-station [2]rotaxane in two different switching modes, Org. Lett. 14 (2012) 1046–1049.
[6] Z.J. Zhang, M. Han, H.Y. Zhang, Y. Liu, A double-leg donor–acceptor molecular elevator: new insight into controlling the distance of two platforms, Org. Lett. 15 (2013) 1698–1701.
[7] V.V. Grushin, Mixed phosphine–phosphine oxide ligands, Chem. Rev. 104 (2004) 1629–1662.
[8] (a) A. Theil, C. Mauve, M.T. Adeline, A. Marinetti, J.P. Sauvage, Phosphoruscontaining [2]catenanes as an example of interlocking chiral structures, Angew. Chem. Int. Ed. 45 (2006) 2104–2107; (b) R. Ahmed, A. Altieri, D.M. D'Souza, et al., Phosphorus-based functional groups as hydrogen bonding templates for rotaxane formation, J. Am. Chem. Soc. 133 (2011) 12304–12310; (c) L. Liu, Y. Liu, P. Liu, et al., Phosphine oxide functional group based three-station molecular shuttle, Chem. Sci. 4 (2013) 1701–1706.
[9] M. Malkoch, K. Schleicher, E. Drockenmuller, et al., Structurally diverse dendritic libraries: a highly efficient functionalization approach using click chemistry, Macromolecules 38 (2005) 3663–3678.
[10] Z.J. Zhang, H.Y. Zhang, H. Wang, Y. Liu, A twin-axial hetero[7]rotaxane, Angew. Chem. Int. Ed. 50 (2011) 10834–10838.
[11] B.T.V. Srinivas, A.R. Maadhur, S. Bojja, Total synthesis of racemic, natural (+) and unnatural (-) scorzocreticin, Tetrahedron 70 (2014) 8161–8167.
[12] Q. Wang, M. Cheng, S. Xiong, et al., P5O functional group-containing cryptands: from supramolecular complexes to poly[2]pseudorotaxanes, Chem. Commun. 51 (2015) 2667–2670.
[13] L.Z. Liu, C.H. He, L. Yang, et al., Novel C1-symmetric chiral crown ethers bearing rosin acids groups: synthesis and enantiomeric recognition for ammonium salts, Tetrahedron 70 (2014) 9545–9553.
[14] Z. Xu, Preparation of supramolecular structures with polymer attached, Faming Zhuanli Shenqing (2014), CN 103665388 A 20140326.
[15] (a) Z.G. Luo, Y. Zhao, F. Xu, et al., Synthesis and thermal properties of novel calix[4]arene derivatives containing 1,2,3-triazole moiety via K2CO3-catalyzed 1,3-dipolar cycloaddition reaction, Chin. Chem. Lett. 25 (2014) 1346–1348; (b) B.T. Zhao, X.M. Zhu, X.H. Chen, Z.N. Yan, W.M. Zhu, Novel clicked tetrathiafulvalene-calix[4]arene assemblies: synthesis and intermolecular electron transfer toward p-chloranil, Chin. Chem. Lett. 24 (2013) 573–577.
[16] H.P. Jacquot de Rouville, J. Iehl, C.J. Bruns, et al., A neutral naphthalene diimide[2]rotaxane, Org. Lett. 14 (2012) 5188–5191.