Synthesis and Conformation of Substituted Chiral Binaphthyl-Azobenzene Cyclic Dyads with Chiroptical Switching Capabilities

Abstract

Optically active binaphthyl-azobenezene cyclic dyads were synthesized to develop a photochromic switching molecule. Azobenezene moieties were cis-trans isomerized by photoirradiation. As a reflection of the structural change, the specific optical rotation and circular dichroism underwent significant shifts. Under certain conditions, the positive-negative and zero-positive (or zero-negative) signals were reversed. Optical rotation may potentially be applied in noise-cancelling nondestructive photoswiches. The conformations were studied by experimental and theoretical methods. The results revealed that the helical chirality, (P) or (M), of the cis-azobenzene moiety was induced by intramolecular axial chirality. The twist direction depended on the axial chirality as well as the azobenzene linkage position to the binaphthyls, but was independent of the identity of substituted groups. 2,2’-Linked-(R)-binaphthyl was found to induce cis-(P)-azobenzene, whereas symmetrically 7,7’-linked-(R)-binaphthyl was found to induce cis-(M)-azobenzene.

1. Introduction

Molecular scaffolds designed for disparate purposes may be linked to enhance the properties of one component or to confer altogether new properties. Stimulus-driven chiroptical switches such as light-, electrically-, pH-, ion-, and temperature-driven switches have received a great deal of attention in the past decade [1,2,3,4,5,6,7,8,9,10,11]. Their high sensitivity and fast response are of great interest for molecular devices. These molecular switches are expected to find application in the fields of noise cancellation data storage, display instrument, and modulator.

Meanwhile, the axially chiral 1,1’-binaphthyl skeletons represented by BINOL [12,13] and BINAP [14,15] have a wide, flexible asymmetric field. Therefore, binaphthyl skeletons have made great contributions to the fields of catalytic asymmetric synthesis [14,15,16,17,18,19,20,21,22,23,24,25,26,27,28], specific molecular recognition [29,30,31,32,33,34,35,36,37,38,39,40,41], helical twisting of liquid crystals [42,43,44,45,46,47,48,49,50,51,52,53,54,55], and computational chemistry [56,57,58,59,60,61,62]. Azobenzenes are frequently used as photochromic components due to their switchable absorption spectra, fluorescence properties, and association constants [63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86]. The cis and trans forms of the azobenzene skeleton differ significantly in length. Therefore, it was thought that the combination of binaphthyls and azobenzenes may lead to novel molecular switches with optical properties that are derived from the chirality of the components.

Previously, Kawamoto et al. described a basic binaphthyl-azobenzene dyad 1 (Figure 1) and its enantiomer [87]. The azobenzene moiety of 1 was efficiently photoisomerized to yield switching behavior, as observed in the intensity of the circular dichroism (CD) and the helical twisting power (HTP) against liquid crystal materials.

Figure 1.

Photoisomerization of binaphthyl-azobenzene dyads 1.

We have continued this work to analyze the photoswitchable optical properties, including absorption, CD, and optical rotation, using substituted binaphthyl-azobenene dyads and their regioisomers [88,89]. Above all, we focused on the switching of the optical rotation, which can be detected at an unabsorbed wavelength, so that the target compounds did not degrade during measurements.

The cis-azobenzene isomers assume an inherent helicity, (P) or (M), caused by the steric hindrance of each of the two benzene rings (Figure 2). The properties of the helicity were not well understood with a notable exception [90], so we proceeded to investigate the twisting patterns of the cis-azobenzene moieties induced by intramolecular chirality transfer from the axial chirality of the binaphthyl units.

Figure 2.

Helicity of the cis-azobenzenes.

2. Results and Discussion

2.1. Binaphthyl-Azobenzene Cyclic Dyads

Binaphthyl-azobenzene cyclic dyads 2–8 used in this study are shown in Figure 3. Their binaphthyl moieties are the axially chiral parts, and the azobenzene moieties are the photochromic parts. Compounds 2–6 have various substituents – benzyloxy, hydroxy, methoxy, and diphenylmethoxy groups – at the 3,3’-positions of the 1,1’-binaphthyl moiety and are linked circulary to the azobenzene moiety at the 2,2’-positions. In contrast, compound 7 has dibenzyloxy groups at the 7,7’-positions, while compound 8 is substituted by 2,2’-dimethoxy groups and is linked to an azobenzene moiety through the 7,7’-positions.

Figure 3.

Opically active binaphthyl-azobenzene cyclic dyads 2–8.

2.2. Synthesis of 2–8

As shown in Scheme 1, 3,3’-disubstituted binaphthyl-azobenzene dyads (R)-2-6 were synthesized starting from optically active (R)-9 [91]. Tandem Williamson synthesis of diol (R)-9 and dibromide 10 afforded cyclic compound (R)-2 in 36% yield. Then debenzylation of (R)-2 with titanium tetrachloride [92,93,94] for 5 min gave (R)-3 in high yield (91%). Using a higher temperature, longer reaction time, or other Lewis acids (e.g. aluminum trichloride or niobium pentachloride) resulted in an extremely low yield (<5%). Additionally, generalized deprotection using palladium-activated carbon (Pd/C) and hydrogen was unsuccessful due to the concomitant reduction of the azobenzene moiety. (R)-4-6 were prepared in moderate yields by coupling (R)-3 with the appropriate halide. In the synthesis of (R)-4 and -5, excess methyl iodide (MeI) and α-bromodiphenylmethane were used, respectively. Although in the synthesis of nonsymmetrical (R)-6, 1.1 equivalents [based on (R)-3] of benzyl bromide were used for preferential monobenzylation, mixtures of desired (R)-6 (35%), unreacted (R)-3 (25%), and dibenzylated (R)-2 (29%) were obtained; they were easily separated by gel permeation chromatography (GPC). (R)-7 and -8 were synthesized by similar manner of synthesis of (R)-2 from 10 and binol (R)-11 [95,96] and -12 [97,98], respectively in moderate yield. Moreover, (S)-2 was prepared from (S)-9 and 10 using the foregoing procedure.

Scheme 1.

Synthetic route to (R)-2-8.

2.3. Photoswitching of Absorption, CD, and NMR Spectra

The change in absorption near 360 nm, which indicated a π−π* transition of the trans form, confirmed the cis-trans isomerization of the azobenzene moiety. The absorption regions of the binaphthyl moiety were below 350 nm [95,96,97,98,99,100]. Hence, every compounds efficiently photoisomerized. As an example, Figure 4c–d and Figure 5c–d show the change in the absorption spectrum of (R)-2 and (R)-7 after irradiation with 365 nm or 436 nm light, respectively. Irradiation at 365 nm caused trans→cis isomerization, whereas irradiation at 436 nm caused the reverse cis→trans isomerization. Both wavelengths gave the same cis-trans isomerization rates of 0.7–0.8 in all compounds. Figure 4a–b and Figure 5a–b show the CD spectra of (R)-2 and (R)-7 after photoirradiation, respectively. The split CD at a short wavelength (around 250 nm), which is attributed mainly to the ¹B_b transition moment of naphthalene rings, reflects the dihedral angle of two naphthalene rings of binaphthyl [101,102,103]. CD spectra of (R)-2 mean the dihedral angles are varied with the compounds and the isomerism. However, further investigation on the short wavelength side is extremely difficult because the azobenzene units also absorb in this region. Meanwhile, the positive/negative region appeared on the long wavelength (400–500 nm) and absorbed only an azobenzene moiety, n-π* band, of (R)-2. Additionally, about (R)-7, the negative/flat region appeared on same wavelength. Hence, we hypothesized that their cis-azobenzene moieties were preferentially-twisted as either (P) or (M) along with the chiral axis of the binaphthyls. This point is discussed later in detail (Section 2.6).

Figure 4.

(a, b) CD spectra of (R)-2. (c, d) Absorption spectra of (R)-2. After 365-nm irradiation (blue line), after 436-nm irradiation (red line). Conditions: 1,4-dioxane (1.0 × 10⁻⁵ M), 20 °C, light path length = 10 mm, irradiation wavelength = 365 nm (10 mW/cm², 100 s) and 436 nm (10 mW/cm², 100 s).

Figure 5.

(a, b) CD spectra of (R)-7. (c, d) Absorption spectra of (R)-7. After 365-nm irradiation (blue line), after 436-nm irradiation (red line). Conditions: 1,4-dioxane (1.0 × 10⁻⁵ M), 20 °C, light path length = 10 mm, irradiation wavelength = 365 nm (10 mW/cm², 100 s) and 436 nm (10 mW/cm², 100 s).

Next, the NMR spectra of the cis- and trans-forms were investigated. In compounds 2–8, isomerism resulted in a pronounced change in the signals of the protons of the binaphthyl parts and their substituents far from the light-driven parts. For example, the chemical shift and signal splitting pattern of the benzyl protons far from the light-driven part of (R)-2 in the ¹H-NMR differed vastly between the cis and trans forms because the signal of (R)-cis-2 appeared as a singlet (5.19 ppm), whereas that of (R)-trans-2 was an AB quartet (4.88 ppm, Δν_AB = 61.7 Hz, J_AB = 11.2 Hz) with Δδ of 0.3 ppm (Figure 6). Like in the examples above, the 3,3’-subsituents of binaphthyls played an important role in the overall conformation of these compounds.

Figure 6.

¹H-NMR spectra of the benzyl protons of (R)-2 after (a) 365 nm-irradiation, (b) 436 nm-irradiation. Conditions: CDCl₃, 1 × 10⁻³ M, 300 MHz, 22 °C, Irradiation: 365 nm (10 mW/cm², 500 s), 436 nm (10 mW/cm², 500 s) in an NMR test tube (ϕ = 5 mm).

2.4. Photoswiching of Optical Rotation

Isomerization also influenced the optical rotation. Table 1 shows the specific optical rotations at the sodium D-line, [α]_D, of (R)-2-8 after photoirradiation until the values were constant (500 seconds). Generally, [α]_D after 365-nm irradiation reflects the CD intensity and Cotton effect pattern at longer wavelengths. The cis-trans ratios were same as those shown in Table 1. The absolute values of [α]_D were lower than those of helicenes and other chiral metallic compounds [104,105,106], but were greater than general axially chiral binaphthyls. Furthermore, [α]_D of (R)-2, -4, and -5 resulted in a sign inversion; (R)-2 showed the largest change (ca. 1,000°). The absolute values of [α]_D of compound (R)-5 remained nearly constant, but the sign was reversed. From the result of (R)-6, both 3- and 3’-substitents, which are bulkier than the hydroxy group, are necessary to realize a sufficient sign inversion. [α]_D of (R)-7 is suited as a switch for zero-rotation/levo-rotation, although the values of (R)-8 remained relatively constant despite efficient isomerization. Hence, a selection of appropriate compounds could yield any type of sign-changing pattern. Moreover, absorption at the sodium D-line (589 nm) did not occur despite analysis at high concentrations and long path-lengths (Figure 7). Thus, target compounds did not degrade during measurement of [α]_D. Hence, a switch for large α adapted from these compounds should realize the development of nondestructive reading of memory devices [107,108,109].

Table 1.

[α]_D and cis-trans ratio after photoirradiation of (R)-2-8.

Compound	[α]D after 365 nm irradiation (deg)	[α]D after 436 nm irradiation (deg)	cis:trans after 365 nm irradiation	cis:trans after 436 nm irradiation
(R)-2	−314	+642	71:29	31:69
(R)-3	−427	−490	65:35	31:69
(R)-4	−370	+248	72:28	22:78
(R)-5	−252	+278	69:31	35:65
(R)-6	−415	−285	68:32	29:71
(R)-7	−544	−7	80:20	20:80
(R)-8	+358	+282	80:20	26:74

Conditions: chloroform, c = 0.10 g/dL, 20 °C, light path length = 10 cm, irradiation wavelength = 365 nm (10 mW/cm², 500 s) and 436 nm (10 mW/cm², 500 s)

Figure 7.

Absorption spectra of concentrated (R)-2 after photo-irradiation; after 365 nm-irradiation (blue line), after 436 nm-irradiation (red line). Conditions: CHCl₃, 0.0126 M (0.01 g/dL), light path length = 10 mm, 20 °C, Irradiation wavelength: 365 nm (10 mW/cm², 500 s), 436 nm (10 mW/cm², 500 s).

2.5. Thermodynamic Parameters of Trans to cis Isomerization Process

The thermodynamic parameters, including rate constants (k), enthalpy of activation (ΔH^‡), entropy of activation (ΔS^‡), and half-life (t_1/2) at 298 K of 2–8 for the cis to trans thermal isomerization were measured or calculated. These parameters were determined according to Eyring equation [110] as discussed in more detail below, and were first-order reactions. For the thermal cis-trans isomerization:

(1)

where [cis]_t and [cis]₀ are the concentrations of the cis-azobenzene at time t and time zero, respectively, and k is the rate constant for the thermal cis-trans isomerization. The first-order rate constant was determined by fitting the experimental data to the equation:

(2)

where A_t, A₀ and A_∞ are the absorbance at 365 nm at time t, time zero and infinite time, respectively.　The first order plots according to equation (2) for the cis-trans thermal isomerization at various temperatures and resulting rate constants are shown in Figure 8 and Table 2, respectively.

Figure 8.

First-order plots for cis to trans thermal isomerization of (R)-2-8. (a) 35 °C, (b) 45 °C, (c) 55 °C, (d) 65 °C.Conditions: 1,4-dioxane, 1.0 × 10⁻⁵ M.

Table 2.

Rate constants k (s⁻¹) of cis to trans isomerization of (R)-2-8.

Compound	k at 35 °C	k at 45 °C	k at 55 °C	k at 65 °C
(R)-2	4.7 × 10−6	9.8 × 10−6	4.0 × 10−5	1.1 × 10−4
(R)-3	5.9 × 10−6	1.8 × 10−5	5.0 × 10−5	1.4 × 10−4
(R)-4	5.0 × 10−6	1.1 × 10−5	4.6 × 10−5	1.1 × 10−4
(R)-5	3.4 × 10−6	1.8 × 10−5	3.1 × 10−5	8.1 × 10−5
(R)-6	5.7 × 10−6	1.3 × 10−5	2.9 × 10−5	8.5 × 10−5
(R)-7	8.2 × 10−6	2.7 × 10−5	4.5 × 10−5	1.4 × 10−4
(R)-8	5.2 × 10−6	1.4 × 10−5	4.2 × 10−5	1.2 × 10−4

Conditions: 1,4-dioxane, 1.0 × 10⁻⁵ M.

Furthermore thermodynamic parameters such as enthalpy of activation (ΔH^‡) and entropy of activation (ΔS^‡) were determined according to the Eyring equation:

(3)

where R, k_B, and h are gas constant, Boltzmann constant, and Planck’s constant, respectively. Substituting into equation (3):

(4)

Figure 9 shows Eyring plots for cis to trans thermal isomerization. The values of ΔH^‡ and ΔS^‡ were obtained from intersect and a slope, respectively, of the linear plot of ln(kh/k_BT) versus 1/T extrapolated to T → ∞ (Table 3).

Figure 9.

Eyring plots for cis to trans thermal isomerization of (R)-2-8.

Table 3.

Enthalpy of activation, entropy of activation, and half-life of (R)-2-8.

Compound	ΔH‡ (kcal/mol)	ΔS‡ (cal/mol·K)	t1/2 at 298 K (h)
(R)-2	22	−13	157
(R)-3	21	−14	120
(R)-4	22	−13	163
(R)-5	20	−17	148
(R)-6	18	−25	101
(R)-7	18	−23	61
(R)-8	21	−15	128

Conditions: 1,4-dioxane, 1.0 × 10⁻⁵ M.

Both ΔH^‡ and ΔS^‡ derived from the rate constants varied slightly for each compound. Although the isomer ratios differ slightly, it is more than probable that the isomerization mechanism is the same for all compounds. Furthermore, most of these compounds had the half-lives at 298 K longer than 100 h, which is extraordinary for azobenzene derivatives. These long lives provide practical advantages for future application.

2.6. Helical Chirality of cis-Azobenzenes

To confirm the hypothesis that the axial chirality of binaphthyl induces the helical chirality of cis-azobenzene (Figure 10), we calculated the optimized geometries and corresponding CD spectra of two diastereomers, the (P)- and (M)-forms at the azobenzene moiety.

Figure 10.

Structures of cis-(P)-azobenzene and cis-(M)-azobenzenelinked to a 1,1’-binaphthyl.

Figure 11a shows the optimized structures of (R)-cis-(P)- and (R)-cis-(M)-2 obtained by the DFT calculations at the B3LYP/6-31G(d) level [101]. Figure 11b shows the CD in the “azobenzene region” (350–600 nm) predicted using these optimized structures by TD-DFT methods at the B3LYP/6-31G(d) level. These results indicated that the (R)-cis-(P)-2 exhibited a negative Cotton effect pattern and (R)-cis-(M)-2 exhibited a positive Cotton effect pattern.

Figure 11.

(a) Optimized structures of (R)-cis-(P)-2 and (R)-cis-(M)-2 obtained by the DFT calculations at the B3LYP/6-31G(d) level under C₂ symmetry. (b) CD calculated by the TD-DFT method with the B3LYP/6-31G(d) level of (R)-cis-(P)-2 (red bar), (R)-cis-(M)-2 (yellow bar), and experimental CD of (R)-2 after 365-nm irradiation (blue line, 1 × 10⁻⁵ M in 1,4-dioxane, 20 °C).

The experimental CD indicated that the preferential configuration of (R)-cis-2 was the (P)-form. Using the same method, (R)-cis-7 was also determined to assume (P)-configuration (Figure 12). In contrast, (R)-cis-8 was determined to assume (M)-configuration (Figure 13). Additionally, the CDs of just the azobenzene moieties in cis-(P)- and cis-(M)-13 were calculated (Figure 14). Similar to (R)-cis-2 -7, and -8, cis-(P)-13 (cis-(M)-13) exhibited a negative (positive) Cotton effect. Therefore, the CD patterns described herein are derived from the innate CD of azobenzene itself and not from binaphthyl-related induced CD [112,113]. Most of the optimized structures were obtained by a calculation under C₂ symmetry. However, the obtained structure of (R)-cis-(M)-7 calculated under C₂ symmetry had an imaginary frequency. Hence, the symmetry was ignored during the optimization of (R)-cis-(M)-7. Additionally, some of the obtained structures using M06/6-31G(d) [114] were unacceptable as it was based on an imaginary frequency.

Figure 12.

(a) Optimized structures of (R)-cis-(P)-7 and (R)-cis-(M)-7 obtained by the DFT calculations at the B3LYP/6-31G(d) level. (b) CD calculated by the TD-DFT method with the B3LYP/6-31G(d) level of (R)-cis-(P)-7 (red bar), (R)-cis-(M)-7 (yellow bar), and experimental CD of (R)-7 after 365-nm irradiation (blue line, 1 × 10⁻⁵ M in 1,4-dioxane, 20 °C).

Figure 13.

(a) Optimized structures of (R)-cis-(P)-8 and (R)-cis-(M)-8 obtained by the DFT calculations at the B3LYP/6-31G(d) level under C₂ symmetry. (b) CD calculated by the TD-DFT method with the B3LYP/6-31G(d) level of (R)-cis-(P)-8 (red bar), (R)-cis-(M)-7 (yellow bar), and experimental CD of (R)-8 after 365-nm irradiation (blue line, 1 × 10⁻⁵ M in 1,4-dioxane, 20 °C).

Figure 14.

(a) Structures of cis-(P)-13 and cis-(M)-13. (b) CD calculated by the TD-DFT method with the B3LYP/6-31G(d) level of cis-(P)-13 (red bar), cis-(M)-13 (yellow bar).

Table 4, which shows the data regarding the asymmetry of the compounds (R)-2-8, (S)-2, and 13, illustrates three points regarding chirality: (1) (R)-2,2’-azobenzene-linked-binaphthyls induced (P)-azobenzene, (2) (S)-2,2’-analogues induced (M)-azobenzene, and (3) 7,7’-analogues acted as pseudo-enantiomers of 2,2’-analogues. A systematic and simple induction of asymmetrical cis-azobenzenes (Figure 15) was structured using common binaphthyl skeletons. These conformational results should assist in future studies on asymmetric azobenzenes.

Table 4.

Sign of experimental and calculated CD, and helical chirality of the cis-azobenzene moiety in 2–8 and 13.

Compound	Sign of Δε[a][b]
	Experimental	Calculated cis-(P)-form	Calculated cis-(M)-form	Chirality of cis-azobenzene[c]
(R)-2	–	–	+	(P)
(R)-3	–	–	+	(P)
(R)-4	–	–	+	(P)
(R)-5	–	–	+	(P)
(R)-6	–	–	+	(P)
(R)-7	–	–	+	(P)
(R)-8	+	–	+	(M)
(S)-2	+	–	+	(M)
1 3		–	+

[a] Sign of Δε at 350–600 nm; [b] Calculated using the TD-DFT method with B3LYP/6-31G(d); [c] These chiralities were determined by comparing the signs between the experimental and computed CD.

Figure 15.

Twisting pattern of cis-azobenzenes induced by axial chirality of binaphthyls.

3. Conclusions

Several axially chiral binaphthyl-azobenzene dyads with substituents were synthesized to examine their reversible photoisomerization and subsequent changes in optical properties. The chiroptical properties of the dyads, CD and optical rotation, changed dramatically. It is notable that reversible positive-negative and zero-positive (zero-negative) chiroptical signals were detected. Moreover, intramolecular chiral transfer from the chiral axis to the helix of the cis-azobenzene moiety was studied empirically and computationally. 2,2’-Linked-(R)-binaphthyl was found to induce cis-(P)-azobenzene, whereas the symmetrical 7,7’-linked-(R)-binaphthyl was found to induce cis-(M)-azobenzene without exception. These results may be useful in designing chiroptical switches as well as in the study of azobenene helicity. Additionally, this work provides a novel use for axially chiral binaphthyls. We are currently studying the development, conformation, and application of specific binaphthyl-azobenzene systems with interesting functions.