Synthesis and structural characterization

In order to achieve the formation of each orientational isomer, we designed axles 2a-c, functionalized with an alkyl substituent bearing a terminal bulky group that cannot slip through the calix[6]arene rims, and with another alkyl chain ending with an OH moiety. This latter head group neither hampers nor alters the threading process, and it is useful for the attachment of the second stopper upon insertion of dumbbells 2a-c into the wheel cavity. These axles were synthesized according to Scheme 4.1. Tosylate 4, obtained from the corresponding diol 3, was first reacted with diphenylacetyl chloride to insert the first stopper. The resulting product 5 was heated to reflux overnight with 4,4′-bipyridine in acetonitrile to give salt 6. Subsequent alkylation with

83 the OH-terminated tosylate 4 afforded the monostoppered axles 2a-c (see experimental for all characterization and synthetic details).

Scheme 4.1: Reagents and conditions: i) TsCl, NEt3, DMAP, CH2Cl2 rt, 3 h; ii) Ph2CHCOCl, THF rt, 12 h; iii) 4,4'-bipyridine, CH3CN reflux, 12 h; iv) CH3CN, reflux, 7 d.

Selective preparation of oriented assemblies from wheel 1 and axles 2a-c was possible because of the inherent complexing properties of 1, explained in detail in the introductive chapter. In fact, previously performed studies demonstrated the selective threading of OH-terminated bipyridinium-based axles from the upper rim of wheel 1.

Indeed, formation of hydrogen bonds between the ureido groups and the anions of the guest favour the insertion of the stoppered axle from the upper rim, whereas the methoxy groups, oriented inward the cavity in the NMR timescale, hamper the access of the dumbbell from the lower rim. For instance, in axle 2a, the diphenylacetic group prevents the threading of the shortest chain C3, and the univocal insertion of chain C12 from the upper rim of the wheel leads to the exclusive formation of pseudorotaxane P[12a] presenting the orientation depicted in Scheme 4.2. This peculiar property was exploited to obtain the desired oriented rotaxanes by a sequential threading-and-stoppering strategy. The same protocol was followed for all the rotaxanes. Wheel 1 was dissolved in toluene and equilibrated for two hours at room temperature with one equivalent of stoppered axle 2a-c. Upon formation of the oriented pseudorotaxane complexes P[12a], P[12b], and P[12c], indicated by the complete dissolution of the otherwise insoluble axle and by the appearance of a typical dark-red color of the resulting homogeneous solution, a slight excess of triethylamine and diphenylacetyl chloride was added. The mixture was then stirred at room temperature overnight¹³. After chromatographic separation, rotaxanes R[C₃C₁₂], R[C₆C₁₆], and R[C₁₆C₆] were isolated in 57, 43, and 40 % yield, respectively. The rotaxane R[C₁₂C₃] was obtained in very poor yield and was contaminated by several

13Both equilibration and stoppering reaction were performed at room temperature to avoid any possible scrambling of the axles into 1, and the consequent formation of mixtures of orientational isomers.

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by-products that prevented its full characterization and was therefore excluded from this study.

Scheme 4.2 Reagents and conditions: i)Toluene, rt, 3 h; ii) Ph2CHCOCl, NEt3, rt, 12 h.

The properties of these non-symmetric rotaxanes were compared with those of the corresponding symmetrical counterparts. R[C₃C₃], R[C₆C₆] and R[C₁₂C₁₂] are known compounds,¹² whereas R[C₁₆C₁₆] was synthesized by equilibrating wheel 1 and symmetrical axle 7 in toluene at room temperature and adding two equivalents of triethylamine and diphenylacetyl chloride (Scheme 4.3).

Scheme 4.3 Reagents and conditions: i) 4,4'-bipyridine, CH3CN reflux,7 d; ii) a) 1, toluene, rt, 3 h.

b) Ph2CHCOCl, NEt3, rt, 12 h.

85 Each synthesized rotaxane was analyzed by NMR techniques to gain information on the structure and the relative orientation of the components (see expanded regions in Figure 4.4 and Experimental for full characterization).

Significantly, in all the rotaxanes the wheel component 1 exhibits a conformational rearrangement typical of a rotaxane-type assembly. This is evidenced, for instance, by the ¹H NMR signal of the NH ureidic protons, involved in hydrogen bonds with anions of the guests, that are remarkably downfield shifted in comparison with the spectrum of free 1, and by the downfield shift endured by the peak attributed to the methoxy groups that, in the threaded form, are oriented outward the cavity. In the spectra of R[C3C12], R[C6C16] and R[C16C6], the methoxy groups of the wheel resonate as a sharp singlet at δ = 3.85, 3.86 and 3.80 ppm, respectively. The singlet shape of this signals is diagnostic for the presence of single orientational isomers. Indeed, the chemical shift of methoxy groups is remarkably affected by the proximity of the lower stopper of the axle, and consequently by the length of the lower alkyl chain of the dumbbell. In the presence of a mixture of orientational isomers, this signal would be split. The orientation of the axle into 1 also affects the chemical shift of several protons of the dumbbell component, especially the methyne protons α and α′ and the O-CH₂ protons 1 and 1′.

Figure 4.4 ¹H NMR spectra (300 MHz, C6D6, 3-6 ppm region) of symmetric and asymmetric rotaxanes. See drawing for labelling.

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Comparison of these signals with those found in the ¹H NMR spectra of the symmetrical rotaxanes R[C₃C₃], R[C₆C₆], R[C₁₂C₁₂] and R[C₁₆C₁₆] provided evidence for the relative orientation of the components. As an example, in R[C3C12], α and α′

protons resonate at δ = 5.30 and 5.07 ppm, respectively, in agreement with the presence of an upward C3 chain and a downward C12 chain. The absence of signals at δ = 5.56 ppm excluded the presence of the opposite orientational isomer with a C3 lower chain. As further evidence, the signal of O-CH2 protons (1) related to the upper chain of R[C3C12] was detected at 3.7 ppm, confirming the presence of a C3 upper chain. As shown in the symmetrical rotaxane R[C12C12], the same signal would be shifted to 4.2 ppm in the opposite orientational isomer with a C12 upper chain. In the same way, the signal of 1′ protons located at δ = 4.06 ppm was consistent with a C12 lower chain. In case of a C3 lower chain, this signal would be shifted to δ = 4.74 ppm.

Furthermore, the signals of # and § protons, as well as 2D NMR correlations (see Experimental), confirmed the relative orientation of the components. Similarly, the univocal orientation of R[C₆C₁₆] and R[C₁₆C₆] was established. Chemical shifts of the most significant and diagnostic signals are gathered in Table 4.1.

Rotaxane O-CH3 α α′ 1 1’ # §

R(C3C12) 3.85 5.30 5.07 3.6-3.8 4.06 3.60 3.60

R(C3C3) 3.7-3.9 5.34 5.56 3.7-4.0 4.74 3.50 3.6-3.7

R(C12C12) 3.90 5.09 5.09 4.1-4.2 4.1-4.2 3.75 3.90

R(C6C16) 3.86 5.13 5.07 4.03 4.03 3.70 3.7-3.8

R(C16C6) 3.80 5.06 5.10 4.02 4.33 3.70 3.70

R(C6C6) 3.84 5.16 5.17 4.08 4.38 3.60 3.70

R(C16C16) 3.86 5.07 5.07 4.03 4.03 3.7-3.8 3.7-3.8

Table 4.1 Chemical shifts (δ, ppm) of some of the most significant signals of synthesized symmetric and non-symmetric rotaxanes; ¹H NMR spectra are recorded in C6D6 at room temperature with a 300 MHz spectrometer.

The obtained rotaxanes were also analyzed via UV-Vis absorption measurements (Figure 4.5).

87 Figure 4.5 Absorption spectra of the rotaxanes in acetonitrile: R[C12C12] (green); R[C3C3] (black) and R[C3C12] (cyan); R[C6C6] (red) and R[C6C16] (pink); R[C16C16] (yellow, below the blue line) and R[C16C6] (blue).

In agreement with previous investigations, all the rotaxanes exhibited two main absorption bands: one, more intense and located in the UV region, ascribed to the absorption of the phenylureido moieties and the bipyridinium core, and a second weaker one around 460 nm, arisen from the charge transfer interaction. Both the energy and the absorption coefficient of this latter band are independent of the length of the axles, suggesting that the donor-acceptor electronic coupling, i.e. the extent of encapsulation of the bipyridinium core in the calixarene cavity, is similar for all the rotaxanes. On the other hand, the coefficient of the band in the UV region is not constant. In particular, rotaxanes bearing chains of the same lenght at the upper rim show comparable bands, thus meaning that the proximity of the stopper to the phenylureido moieties has an influence on their absorption.