Chemistry and Photochemistry of 2, 6-Bis (2-hydroxybenzilidene

Article pubs.acs.org/JPCA

Chemistry and Photochemistry of 2,6-Bis(2hydroxybenzilidene)cyclohexanone. An Example of a Compound Following the Anthocyanins Network of Chemical Reactions Artur J. Moro,† Ana-Maria Pana,‡ Liliana Cseh,*,‡ Otilia Costisor,‡ Jorge Parola,† L. Cunha-Silva,§ Rakesh Puttreddy,∥ Kari Rissanen,∥ and Fernando Pina*,† †

REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Monte de Caparica, Portugal ‡ Institute of Chemistry Timisoara of Romanian Academy, 24 MihaiViteazul Bvd, 300223 Timisoara, Romania § REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007 Porto, Portugal ∥ Department of Chemistry, Nanoscience Center, University of Jyväskylä, 40014 Jyväskylä, Finland S Supporting Information *

ABSTRACT: The kinetics and thermodynamics of the 2,6bis(2-hydroxybenzilidene)cyclohexanone chemical reactions network was studied at different pH values using NMR, UV−vis, continuous irradiation, and flash photolysis. The chemical behavior of the system partially resembles anthocyanins and their analogue compounds. 2,6-Bis(2hydroxybenzilidene)cyclohexanone exhibits a slow color change from yellow to red styrylflavylium under extreme acidic conditions. The rate constant for this process (5 × 10−5 s−1) is pH independent and controlled by the cis−trans isomerization barrier. However, the interesting feature is the appearance of the colorless compound, 7,8-dihydro-6H-chromeno[3,2-d]xanthene, isolated from solutions of acid to neutral range, characterized by 1H NMR and single crystal X-ray diffraction. Light absorption by 2,6-bis(2-hydroxybenzilidene)cyclohexanone solutions immediately after preparation exclusively results in cis-isomer as photoproduct, which via hemiketal formation yields (i) red styrylflavylium by dehydration under extremely acidic solutions (pH < 1) and (ii) colorless 7,8-dihydro6H-chromeno[3,2-d]xanthene by cyclization in solutions of acid to neutral range.

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INTRODUCTION

hemiketal is in fast equilibrium with cis-chalcone, Cc (usually in the subseconds lifetime), and the (final) equilibrium is reached upon formation of trans-chalcone through the isomerization. One interesting property of flavylium related compounds is the possibility of achieving photochromism from irradiation of the trans-chalcone form. It was reported that besides flavylium derivatives, some families of structurally related compounds follow an identical network of chemical reactions as the one shown in Scheme 1. It is the case of the so-called styrylflavylium and naphthoflavylium, Scheme 2.6−8 In the frame of our research to identify the anthocyanins’ network of chemical reactions in other types of compounds with the aim of discover new photochromic systems, it was reported that 2,2′-dihydroxychalcones have the ability to form flavylium cations through the same mechanisms. The transchalcone isomerizes to the cis-chalcone, this one closes the ring

Flavylium derivatives are an important family of compounds that comprise anthocyanins and other natural derivatives, as well as a variety of synthetic ones. Existence of a common chemical reaction network is the remarkable feature in these compounds, one such example for malvidin-3-glucoside (oenin) is shown in Scheme 1.1−3 The flavylium cation is stable only at very acidic pH values. Raising the pH leads to the formation of the quinoidal base via proton transfer in competition with hydration of the flavylium cation to originate the hemiketal. The former reaction is by far the fastest of the network and by consequence the quinoidal base is formed immediately after a direct pH jump, here on defined as the addition of base to equilibrated solutions of the flavylium cation at very low pH values. As shown by Brouillard and Dubois,4,5 the quinoidal base does not react in acidic to neutral medium. Consequently, the fraction of flavylium cation that is available to form hemiketal and allow the system to go forward (up to trans-chalcone, Ct) decreases with increasing pH. Quinoidal base is thus a kinetic product that retards the formation of the final equilibrium. On the other hand, the © 2014 American Chemical Society

Received: June 5, 2014 Revised: July 23, 2014 Published: July 24, 2014 6208

dx.doi.org/10.1021/jp505533b | J. Phys. Chem. A 2014, 118, 6208−6215

The Journal of Physical Chemistry A

Article

Scheme 1. Network of Chemical Reactions of Anthocyanins, As Exemplified for Oenin

Scheme 2. Flavylium Derived and Flavylium Analogue Compounds Following the Same Network of Chemical Reactions

Scheme 3. Formation of Two Flavylium Cations (Marked in Red and Blue) from Asymmetric 2,2′-Dihydroxychalcones, through the Same Mechanism as the One Followed by Anthocyanins and Related Compounds7

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to give hemiketal, which dehydrates, leading to the flavylium cation. In the case of asymmetric 2,2′-dihydroxychalcones, two different flavylium compounds are obtained, Scheme 3.7 Besides the mechanism shown in Scheme 1 (identical to anthocyanins), kinetic evidence for the coexistence of an alternative mechanism which involves the formation of a ketal intermediate was achieved.7,9 This intermediate (not isolated) was proposed to explain the interconversion of the two styrylflavylium isomers. Very recently some of us reported evidence for the formation of flavylium cation from 2,6-bis(2-hydroxybenzilidene)cyclohexanone (hereafter referred to as DHCH), Scheme 4.10

temperature and by consequence the compound can be stocked at higher pH values. In contrast, solutions of the compound DHCH in methanol/ water (1:1) are not stable and in a slow process evolve to a colorless species according to spectral modifications shown in Figure 1B. The process takes place at the same rate within a pH range of 4.2 < pH < 6.4. The spectral changes indicate that the trans-chalcone leads to a product lacking of absorption in the visible, suggesting a disruption of the π−π* conjugation of the aromatic rings. This behavior has been observed in the flavylium reaction network for the hemiketal species. Regarding the kinetic process, its rate is relatively low and pH independent, compatible with a kinetic step controlled by the cis−trans isomerization. The formation of the colorless product in the reaction network supports the kinetics reported in Figure 1B and was followed by 1H NMR. The assignment of the peaks to the structure of the Ct form of DHCH, Scheme 5, was previously reported.10 Evolution of the NMR spectra over long periods of time (up to 2 weeks) is shown in Figure 2. During this period, the solution evolves from yellow to colorless, hailing crystals suitable for single crystal X-ray analysis. Redissolution of the crystals in CD3OD yielded spectrum (7) which, by comparison with spectrum (6), proves that the crystals represent the thermodynamic product of the system under these conditions. The analysis of the 13C NMR spectrum (see Supporting Information, Figure S3) shows only 10 signals, a clear indication that the structure is very symmetric. Full characterization and assignment of 1H and 13C signals was achieved with HSQC and HMBC spectra (Table S1, Supporting Information) and allowed us to identify a spiropyrane-like structure linked by a propyl bridge, 7,8dihydro-6H-chromeno[3,2-d]xanthene (Figure 3), henceforth named B−B. The crystal structure of B−B solved in the orthorhombic space group Pbcn lies on 2-fold axis supporting our 1H NMR and 13C NMR spectra assignment. As shown in Figure 3, the benzopyrans are connected at carbon C9 in near tetrahedral

Scheme 4. Chemical Structure of 2,6-Bis(2hydroxybenzilidene)cyclohexanone (DHCH)

This compound is a symmetric 2,2′-dihydroxychalcone with the two α carbons adjacent to the ketone linked by an aliphatic bridge that confers more rigidity to the structure. The aim of this work is to study the kinetics and thermodynamics of the chemical reaction network for DHCH, particularly the isolation and characterization of the ketal intermediate, to confirm the existence of spironaphthopyranes as intermediates in the chemistry of 2,2′-dihydroxychalcones, thereby linking the two families of compounds.

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RESULTS AND DISCUSSION The absorption spectra of DHCH as a function of pH, Figure 1A, is compatible with a diprotic acid with acidity constants equal to pKCt/Ct− = 9.4 and pKCt−/Ct2− = 10.9. As observed in other polyphenols, the successive deprotonation gives rise to a red shift of the absorption bands. The solutions at basic pH values are stable for long time periods (weeks) at room

Figure 1. (A) Titration of the trans-chalcones of DHCH in basic medium, methanol/water (1:1), 0.05 mM. (B) Spectral variations of the compound DHCH 0.1 mM, upon dissolution in methanol/water (1:1) (natural pH = 6.5). The value of the rate constant in the range 4.2 < pH < 6.4 is the same within the experimental error. 6210



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Figure 2. NMR spectra of DHCH in CD3OD upon dissolution and followed over time: (1) 5 min, (2) 7 h, (3) 15 h, (4) 43 h, (5) 94 h, and (6) 2 weeks after dissolution. Spectrum (7) corresponds to the 1H NMR of crystals of B−B.

propylene [110.9(1)°] bridge of previously reported spiro aromatic pyrans.12 The benzene and the pyran ring are nearly coplanar with a nonbonded O1−O1′ distance of ca. 2.317 Å. Furthermore, the bond lengths and bond angles around the spiro-carbon C9 of B−B are similar to the values reported for spirobinapthopyran molecule with propylene bridge.12 Solutions of B−B (equilibrated at natural pH) were submitted to pH jumps to the basic (up to pH = 12) and acid regions (up to [H3O+] = 2 M). Although in basic to acid medium B−B is stable, in very acidic conditions it is rapidly transformed into a flavylium cation via formation of hemiketal B (Scheme 5). The absorption spectra taken 2 min upon the pH jumps from B−B at natural pH to lower pH values are represented in Figure 4. The pH dependence of the absorbance at 504 nm in the inset of Figure 4 is compatible with a single acid−base equilibrium with apparent pK′a= 0.3. The kinetic process for the transformation of B−B into the flavylium cation was studied as a function of pH and is reported in Figure 5. The rate constants follow a first-order kinetic process and have peculiar pH dependence as shown in Figure 5B. At lower pH values there is a direct proportionality between the value of the rate constant and the proton concentration, whereas at higher pH values the rate of flavylium cation formation increases with decreasing proton concentration. To clarify this question, a solution of DHCH was brought to pH = 0.3 and irradiated at 366 nm. An aliquot was kept in the dark and used as reference. Though the solution in the dark

Figure 3. Crystal structure of B−B with selected atom labeling. Selected bond lengths (Å) and bond angles (deg): C1−O1 = 1.3811(15), C9−O9 = 1.4368(14), O1−C9−O1′ = 107.48(14), O1− C9−C8′ = 107.03(6), O1−C9−C8 = 112.50(6), C8−C9−C8 = 110.35(15).

geometry [τ4 = 0.95]11 and are linked by a propylene chain at C8 and C8′. The twist at the spiro-carbon C9 is a commonly observed phenomena with C8−C9−C8′ angles being characteristic of the alkylene chain. Hence, the C8−C9−C8′ [110.35(15)°] angles in B−B fall between the ethylene [104.3(2)°] and butylene [118.2(3)°] and are similar to the 6211



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Scheme 5. Proposed Kinetic Scheme for the DHCH Network of Chemical Reactions

slowly evolves to flavylium cation with a rate constant of 7 × 10−5 s−1 at pH = 0.5 (in good agreement with the thermal rate constant in Figure 1B for the cis−trans isomerization barrier), the flavylium cation is formed after a few seconds of irradiation, Figure 6A. Moreover, by irradiating a fresh solution of DHCH at natural pH, the photoproduct exhibits the same absorption spectrum of the cyclic ketal B−B, Figure 6B. This result is compatible with a photochemical overcoming of the cis−trans isomerization barrier and supports that the rate-determining step of the flavylium formation from DHCH is the cis−trans isomerization. Additional information was obtained by means of flash photolysis experiments, Figure 7. In these experiments, freshly prepared solutions of DHCH are submitted to a flash and the absorbance is monitored at two wavelengths where flavylium cation (500 nm) and trans-chalcone (360 nm) absorb. Based on the experimental data regarding flavylium compounds and according to other results reported in literature13,14 concerning the photoinduced cis−trans isomerization, it is reasonable to consider that Cc is formed immediately after the flash. According to Figure 7 two successive kinetic processes take place after the flash. The bleaching of the absorption at 360 nm can in principle be attributed to the disappearance of Cc. This process is

Figure 4. Spectral variations observed upon pH jumps from equilibrated solutions of 0.1 mM B−B in water/methanol (1:1) at natural pH to lower pH values. The spectra were collected 2 min after the mixing. No significant changes on the absorption spectra were observed after 1 day.

Figure 5. (A) Trace for the flavylium formation upon a pH jump of B−B at natural pH to pH = 0.6. (B) Representation of the observed rate constants for AH+ appearance from B−B as a function of pH as determined upon pH jumps (●) and from flash photolysis of Ct (○). Fitting was achieved with eq A6 for Ka < 10−4 M, Kh = 3.3 × 10−3 M, k−b < 0.001 s−1, kb/k−h < 3 × 10−4, kH−b = 0.065 M−1 s−1, kHb = 0.05 M−1 s−1. 6212



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Figure 6. (A) Spectral variations upon irradiation of DHCH at 365 nm, 0.05 mM pH = 0, reaction quantum yield, Φ = 0.31. (B) The same at natural pH, Φ = 0.43. I0 = 2.6 × 10−7 einstein min−1.

Figure 7. (A) Flash photolysis of DHCH at pH = 1.49. In both cases the process is biexponential. Fitting was achieved for the rate constants 0.46 and 0.06 s−1. (B) pH dependence of the faster rate constant. Fitting was achieved for 0.06 + 20[H+] s−1. The slowest process is fitted according to the right branch of Figure 5B.

formation of B−B from B. One significant aspect is the coincidence of the slowest process of the flash photolysis with the right branch of the kinetic step represented in Figure 5B. In other words, the disappearance of the flavylium cation during the slowest kinetic step of the flash photolysis to form B−B is the same as the appearance of flavylium cation from B−B upon a pH jump. These results can be interpreted if the following sequence of reactions is considered AH+ ⇌ B (Cc) ⇌ B−B. A kinetic expression can be deduced considering the steady state hypothesis for the species B (Cc), eq 1 (see Supporting Inofrmation for detailed description).

biexponential. At the same time, the trace at 500 nm reveals the appearance of flavylium cation followed by its disappearance. Both traces (at 500 and 360 nm) can be fitted with the same two rate constants. These results can be interpreted by considering that in the fast process flavylium is formed from Cc via B. The question is which of these two steps, tautomerization or hydration, is the rate-determining step. Representation of the pH dependence of the faster process of the flash photolysis is shown in Figure 7B. In the case of a ratedetermining step by tautomerization, the pH dependence would be due to the acidic catalysis, whereas in the case of hydration, the rate would be controlled by the term k−h[H+]. The data shown above suggest that the process is controlled by the hydration reaction. Fitting can be achieved for kh = 0.06 s−1 and k−h = 20 M−1 s−1, leading to the respective equilibrium constant Kh= 3.3 × 10−3 M. At this point the species AH+, B, and Cc are in pseudoequilibrium. The subsequent disappearance of the flavylium cation can be explained if a new (and slower) channel appears. A possible explanation is the

kobs =

[H+] K [H+] + K a h

+ (k −b + k −Hb[H+])[H+]

[H+] +

k b + k bH[H+] k −h

(1)

The data reported in Figure 5B can be fitted with the equilibrium and rate constants shown in Table 1. 6213



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Table 1. Rate and Equilibrium Constants of DHCH Network pKa >4

Kh (M) −3

3.3 × 10

kh (s−1) 0.065

a

k−h (M−1 s−1) a

20

kb/k−h (M)

kb (s−1)

k−b s−1(s−1)

KbH (M−1 s−1)

k‑bH (M−1 s−1)

Chemistry and Photochemistry of 2, 6-Bis (2-hydroxybenzilidene

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