2,2′-Spirobis[chromene] Derivatives Chemistry ... - ACS Publications

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2,2′-Spirobis[chromene] Derivatives Chemistry and Their Relation with the Multistate System of Anthocyanins Artur J. Moro,† A. Jorge Parola,† Fernando Pina,*,† Ana-Maria Pana,‡ Valentin Badea,§ Iulia Pausescu,‡ Sergiu Shova,∥ and Liliana Cseh*,‡

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LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal ‡ Institute of Chemistry Timisoara of Romanian Academy, 24 M. Viteazu Bvd, 300223 Timisoara, Romania § Faculty of Industrial Chemistry and Environmental Engineering, University Politehnica Timisoara, 6 V. Parvan Bvd, 300223 Timisoara, Romania ∥ Petru Poni Institute of Macromolecular Chemistry, Inorganic Chemistry, 41A Aleea Gr. Ghica Voda, 700487 Iasi, Romania S Supporting Information *

ABSTRACT: The chemistry of 2,2′-spirobis[chromene] derivatives is intimately related to the one of anthocyanins and similar compounds. The 2,2′-spirobis[chromene] species plays a central role in the network of chemical reactions connecting two different flavylium-based multistate systems. In the present work, a new asymmetric 2,2′-spirobis[chromene] intermediate possessing a constrained propylenic bridge between carbons 3 and 3′ was isolated and its role as a pivot in the anthocyanins-type multistate of chemical reactions was investigated by the conjugation of absorption spectroscopy, stopped-flow, NMR, and X-ray crystallography. It was confirmed that the propylenic bridge is essential to stabilize the spirobis[chromene] species. Furthermore, under acidic conditions, two cis−trans styrylflavylium isomers were identified, which could be interconverted directly into one another with light. This is the first report of styrylflavylium cations with photoisomerization on the styryl moiety.

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INTRODUCTION Nature selected the multistate of species resulting from anthocyanins to confer color to most flowers and fruits.1 The multistate is constituted by a pH dependent sequence of chemical reactions that in moderately acidic medium involves five different chemical species, as exemplified for malvidin-3-Oglucoside (oenin), Scheme 1.2,3 At sufficiently acidic medium the red flavylium cation, AH+, is the dominant species (Chatelier’s principle), and thus anthocyanins (and related compounds)4 are generally stored in vitro in their flavylium form at pH < 1. The multistate system is studied by following the reactions that take place upon addition of base (direct pH jumps). After a direct pH jump, if the pH is sufficiently high, two parallel reactions may occur, (i) proton transfer to form the quinoidal base, A, (ii) hydration in position 2 leading to hemiketal, B. Proton transfer is, by far, the fastest reaction of the multistate and consequently, A is formed during the mixing time of the solutions. In all the subsequent kinetic processes, AH+/A behave as a single species. After the breakthrough of Brouillard and Dubois,5 who discovered that in acidic medium A does not react, it was clear that this latter species is a kinetic product that may form B only via AH+. The hemiketal could also open its ring, yielding cis-chalcone, which in turn, can isomerize to the trans-chalcone. The kinetic © 2017 American Chemical Society

processes and the pH dependent mole fraction distribution of the different species are dramatically dependent on the nature and position of the substituents. Related to the flavylium cation are the so-called styrylflavylium compounds (2-styryl-1-benzopyrylium derivatives) that follow exactly the same multistate.2 In theory, each of the species could have a cis−trans isomerization in the pendent styryl arm (that includes ring B) although, to our knowledge, no experimental evidence for this possibility has been found so far.6 Introduction of a hydroxyl group in position 2′ of ring B of a styrylflavylium, as shown in Scheme 2, increases the number of species since there are two possibilities of forming cis-chalcone and closing the ring, leading to different styrylflavylium isomers. A particularly interesting mechanistic aspect was the previously reported kinetic evidence for a transient intermediate, the 2,2′spirobis[chromene] species, that links both flavylium systems, as represented in Scheme 2.6 The development of multistate/ multiresponsive systems, i.e., molecular reaction networks with several species which can be interconverted by different external stimuli such as light, heat, ions, or electrons (each Received: March 17, 2017 Published: April 25, 2017 5301

DOI: 10.1021/acs.joc.7b00634 J. Org. Chem. 2017, 82, 5301−5309

Article

The Journal of Organic Chemistry Scheme 1. Multistate of Chemical Reactions of Malvidin-3-O-glucoside (oenin) in Water

In spite of the numerous reported synthesis of 2,2′spirobis[chromene] derivatives,10−13 in particular a few possessing hydroxyl substituents,14,15 no studies in water or water−organic solvent mixtures have been reported, except the examples given in Schemes 26 and 3a.16 The question is that the study of the anthocyanin type multistate that are intrinsic of 2,2′-spirobis[chromene] derivatives can only be highlighted in the presence of water. In the work reported in Scheme 2, the asymmetric 2,2′-spirobis[chromen]-7-ol intermediate was not isolated nor its absorption spectrum obtained due to the transient nature of this species in the presence of water. Recently, we were able to isolate and obtain a crystal structure of a similar (but symmetric) 2,2′-spirobis[chromen] form, represented in Scheme 3a, and studied the respective anthocyanin-type multistate of chemical reactions.16 The propylenic bridge linking positions 3 and 3′ could be the key factor to favor the isolation of the 2,2′-spirobis[chromene] intermediate whenever water is present as solvent or cosolvent. Based on these evidence we synthesized the asymmetric bis2,2′-dihydroxychalcone similar to the one in Scheme 2 (CtCt, Scheme 3b) but possessing a propylenic bridge, with the aim of isolating the corresponding asymmetric 2,2′-spirobis[chromene] intermediate and study the respective multistate of chemical reactions.

Scheme 2. Asymmetric 2,2′-Spirobis[chromen]-7-ol Ketal Intermediate (Bottom) and Chalcone (Top) Connect Two Different Styrylflavylium Isomers: 2-(2,4-Dihydroxystyryl)1-benzopyrylium (Blue) and 7-Hydroxy-2-(2-hydroxystyryl)1-benzopyrylium (Red)

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RESULTS AND DISCUSSION

Scheme 4 summarizes all possible interconversion pathways of the multistate of species taking place from the central spiro compound, including the photochemistry of the flavylium cations. The scheme is based on previous experience accumulated for the flavylium compounds in particular the so-called styrylflavylium cations,2 as well as the most recent proposal6 and finally isolation and identification16 of a 2,2′spirobis[chromene] intermediate for these type of compounds. In Scheme 4, the spiro intermediate due to its asymmetry (in contrast with the spiro in Scheme 3a)16 may in theory give two different hemiketal compounds or quinoidal bases leading to flavylium cations or chalcones, respectively, in acidic or moderately acid to basic solutions. In addition there is the possibility of the existence of a cis−trans isomerization of the pendent arm in each of the isomers due to the restraint for the

state is a thermodynamic or kinetically trapped frame of the equilibria network), is a key point to systems chemistry with potential applications in several fields, namely molecular-level computing.7−9

Scheme 3. (a) Symmetric 2,2′-Spirobis[chromene] Ketal Intermediate 7,8-Dihydro-6H-chromeno[3,2-d]xanthene16 and (b) Transformation of the Asymmetric Chalcone (2E,6E)-2-(2,4-Dihydroxybenzylidene)-6-(2hydroxybenzylidene)cyclohexanone in the Corresponding Asymmetric 2,2′-Spirobis[chromene] Derivative 7,8-Dihydro-6Hchromeno[3,2-d]xanthen-2-ol

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Scheme 4. All Possible Pathways and Species of the Multistate that Can Be Originated from the Spiro Compound in Acid to Neutral Solutionsa

a Four horizontal anthocyanin type multistate can in theory be operated. Differently from previous results reported for the analog 2,2′-spirobis[chromene] intermediate lacking the 3,3′ propylenic bridge, no experimental evidence was achieved in the present work for the multistate in gray.

CD3OD:DClO4 95:5, v/v) is a mixture of a major species (FL2) and a minor species of the initial flavylium (FL1), respectively 83 and 17%. The equilibrated solution of the compound at pH = 1.1 was irradiated with a series of cutoff filters from 280 to 515 nm, see Supporting Information, and the fraction of FL1 formation at longer wavelengths becomes smaller. In other words, shifting the irradiation wavelength to higher values permits to FL1 formed by irradiation of FL2 compete more efficiently for the irradiation light. This leads to an increase of the reverse photochemical reaction that converts FL1 in FL2, giving a photostationary state with less FL1. The quantum yield for the conversion of FL1 into FL2 is 0.065. Conversely the spiro form is photochemically stable in this mixture of solvents. The question that we have to answer regards the structures of the two flavylium cations. Are they cis−trans isomers on the pendent arm (the two flavylium cations in red or the two in

pendent arm rotation caused by the bridge. In this work, in contrast with the equivalent compound lacking the bridge,6 we did not get experimental evidence in Scheme 4 for the sequence of reactions in gray. Flavylium Interconversion. Stopped-flow measurements carried out by mixing the spiro compound dissolved in ethanol/ water (1:4) with ethanol/0.2 M HCl (1:4) show the appearance of an absorption spectrum characteristic of a flavylium cation (FL1), Figure 1a. The process can be fitted with a monoexponential of lifetime 0.23 s−1. A similar experiment that followed in a common spectrophotometer shows the time evolution of this flavylium cation, taking place according to a monoexponential with rate constant 4 × 10−4 s−1 to another absorption band with maximum at 500 nm compatible with the conversion of the initial flavylium compound to another flavylium species (FL2). The NMR data (see below) proved that the equilibrium (in 5303


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Figure 1. (a) Stopped-flow measurements carried out by mixing the spiro compound dissolved in ethanol/water (1:4) with ethanol/0.2 M HCl (1:4); fitting was achieved with a monoexponential with rate constant 0.23 s−1. (b) Identical experiment followed by a common spectrophotometer. Initial absorbance maximum 550 nm; final 500 nm. The kinetics is fitted with a monoexponential with rate constant 4 × 10−4 s−1. (c) Irradiation of the compound FL2 at pH = 1.1 (obtained in Figure 1b) with a cutoff filter of 435 nm leads to the initial compound FL1.

Figure 2. X-ray structure of FL2 cation with atom labeling scheme and thermal ellipsoids at 30% probability level (left), and the respective 3D architecture from a fragment of crystal packing viewed along the a axis; π−π stacked aromatic rings are highlighted in orange (right).

Several 1H NMR spectra were run at 298 K until the equilibrium was reached (Figure S9, Supporting Information). In the equilibrated sample, COSY, 13C, HSQC, HMBC, and NOESY spectra were run allowing full assignment of 1H and 13 C assignments for each species (Figures S10−S14 and Table S2, Supporting Information). The 1 H NMR spectrum shows two sets of peaks corresponding to ca. 17% of the initial compound and 83% of the new compound formed upon thermal equilibration at 298 K. The initial spectrum and that of the new compound show exactly the same pattern: two singlets assigned to protons 5 and 14 (see Table S2 for structures); one ABCD set corresponding to four consecutive protons in the same aromatic ring; an ACD set corresponding to three protons in relative positions 1, 2, and 4 in the same aromatic ring and a set of aliphatic protons corresponding to the propylene bridge. This would be compatible with two structural isomeric flavylium cations (red and gray colors in Scheme 4) but also with two geometric cis-trans isomers of the same structural isomer (FL1 and FL2 in Scheme 4 and in Table S2 of the Supporting Information). The singlet at the lowest field was assigned to H5 on both isomers on the basis of the expected lowest electron density on this position and in accordance with many published flavylium derivatives.2 The COSY spectra

gray in Scheme 4) or two isomers having a different pattern of hydroxyl substitution (flavylium cations in red and gray in Scheme 4), as reported in for the analogous compound lacking the propylenic bridge6 (Scheme 2)? In previous work, a similar flavylium cation interconversion was observed but it was unequivocally shown that both flavylium cations had a different substitution pattern of the hydroxyl groups (see Scheme 2).6 Moreover, in both flavylium cations the styryl double bond was in the trans configuration, as indicated by the high coupling constants between protons α and β.6 In the present compound, the lack of proton α due the presence of the propylenic bridge precludes this analysis and other arguments are needed to identify the species involved. The NMR results and the crystal structure as well as the kinetic behavior together proved that FL2 is the trans isomer and FL1 the cis. NMR and Crystal Structure of FL2. A sample for NMR was prepared by dissolving the synthesized 2,2′-spirobis[chromene] 5a,6,7,8,8a,9-hexahydro-5H-chromeno[3,2-d]xanthen-2-ol in 700 μL of CD3OD followed by addition of 40 μL of 68% (w/w) DClO4. A red-violet color developed upon addition of acid (FL1) that changed to red over time (FL2), in consonance with the observed spectral data in Figure 1b where a blue shift is observed on going from FL1 to FL2. 5304


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Figure 3. Spectral variations of equilibrated solutions of the compound in the pH range (a) 1 < pH < 5.4; (b) 5.4 < pH < 13; (c) mole fraction distribution of the several species, (○) 580 nm, (●) 500 nm, (■) 300 nm. Fitting was achieved for the following pKas: 2.4. 10.1, 12.3.

Figure 4. (a) Absorption variations after a direct pH jump from pH = 1.0 to 6.4; red line corresponds to ca. 60 ms; (b) kinetics of the process followed at 520 nm. The system at this stage reached the equilibrium. The faster rate constant is an estimation because it is based in two points only; (c) kinetic scheme upon a direct pH jump to pH = 6.4.

consisting of FL2 cations, ClO4− anions and cocrystallized water molecules in 1:1:1 ratio. The charge balance and the composition of the crystal are in agreement with the formation of species FL2ClO4·H2O. The structure of FL2 cation is shown in Figure 2, while the bond lengths and angles are summarized in Table S4 (Supporting Information). The analysis of the crystal packing revealed a three-dimensional supramolecular network which is formed due to O−H···O intermolecular hydrogen bonding and π−π stacking interactions. The centroidto-centroid distance between adjacent aromatic rings is of 3.616(7) Å with shift distance of 0.986(7) Å. A view of the crystal structure packing is shown in Figure 2b. This 3D architecture shows the presence of quite large channels (14.0 × 5.7 Å) running along a crystallographic axis, which accommodate out-of-sphere anions and disordered cocrystallized water molecules. The Equilibrium. The absorption spectra of equilibrated solutions of the compound are shown in Figure 3. According to Figure 3a, equilibrated solutions of the compound between 1 < pH < 5.4 are compatible with an equilibrium involving the flavylium cations and a species not absorbing in the visible with

allowed the establishment of scalar connections inside each proton set. Full assignment of 1H and 13C peaks with identification of the structures was made on the basis of the HMBC and NOESY spectra. The predominant isomer was assigned to structure FL2 in Scheme 4 (and in Table S1) on the basis of the following: (i) from HMBC spectra scalar connections H5 < > C7, H7 < > C5, H14 < > C16, and H16 < > C14 define the position of the rings with ABCD and ACD sets relative to the pyrylium ring; (ii) in NOESY spectra spatial connections between H5 < > H7 and H14 < > H16 confirm this hypothesis. The minor isomer could be assigned to structure FL1 on the basis of similar observed connections: (i) HMBC spectra scalar connections H14 < > C16 and H16 < > C14; (ii) NOESY spectra spatial connection H14 < > H16. This proves that the two compounds are cis-trans isomers of the same structural isomer. X-ray single crystal diffraction of an isolated flavylium confirms that the trans isomer is the predominant species in the equilibrium. Monocrystals suitable for X-ray diffraction were isolated from the NMR tube under acidic conditions. According to single crystal X-ray diffraction the crystal has an ionic structure 5305


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Figure 5. (a) Spectral variations after a direct pH jump from 1 to 1.95; (b) spectral decomposition was achieved combining the individual spectra of FL1, FL2, and spiro with a contribution of 34, 5, and 61% for each of the species, respectively. The system at this stage reached the equilibrium; (c) kinetic scheme upon a direct pH jump to 1.95.

can be decomposed with a contribution of trans-quinoidal base and spiro. The formation of the spiro from the cis-quinoidal base is expected, because this base exhibits the right conformation to close the ring (process (ii) in Figure 4c). Moreover, it is in accordance with the fact that dissolution of the spiro compound in acidic medium gives FL1 very fast. The third and slower process could be attributed to the formation of more spiro compound from trans quinoidal base via cis quinoidal base, a process that should be controlled by the trans to cis isomerization of the bases (process (iii) in Figure 4c). No significant kinetic spectral modifications occur in longer time scales. Figure 4c summarizes this kinetic process. A similar pH jump to pH = 1.95 is represented in Figure 5. The initial absorption can be fitted with the contribution of FL2 together with the spiro form. This can be explained by considering that all FL1 was very rapidly transformed in spiro, most probably via cis quinoidal base. The kinetic process leads to a mixture of spiro, FL1 (major), and FL2 (minor) and no significant further spectral changes have been observed after several hours. This permits to conclude that the kinetic process is due to the conversion of FL2 into spiro in principle via FL1 and the respective quinoidal base. At this pH value, an equilibrium between these two forms is reached in accordance to the data of Figure 2b. The kinetic scheme is summarized in Figure 5c. More information can be achieved by performing reverse pH jumps. Figure 6a shows the spectral variations accompanying a reverse pH jump from pH = 12 to 5.1. Two consecutive first order processes take place. The system was analyzed through two consecutive kinetic processes R → I → P. The first absorption immediately after the pH jump is compatible with trans-chalcone obtained by protonation (during the mixing time of the stopped flow) of the ionized trans-chalcone, the equilibrium species at pH = 12.0. The first kinetic step corresponds to the formation of a species absorbing in the visible which, by its position, could be attributed to a transquinoidal base, the same species of the intermediate shown in Figure 2a. The rate-determining step of this process (i) could be assigned to the trans to cis isomerization step. On the other hand the second process that leads to the spiro occurs with a rate constant of 0.16 s−1. This last process could be attributed to the trans to cis isomerization of the quinoidal base (ii).

a spectrum similar to the one of the spiro compound reported in a previous paper.16 In the interval 5.4 < pH < 13 in Figure 3b, it is observed the large pH range of stabilization of the spiro species. Increasing the pH, a slight red shift of the spiro absorption band is compatible with the deprotonation of the phenol substituent. At more basic pH values, an isosbestic point (315 nm) and the shape and position of the spectra indicate the existence of one species in equilibrium with the ionized spiro. As in previous flavylium and styrylflavylium multistates this can be attributed to the ionized chalcones, Ct2− and Ct3−. The small absorption in the visible accompanying the formation of spiro and ionized spiro can be attributed to a small fraction of quinoidal bases and their deprotonated forms. The species present under basic conditions were characterized by NMR, by preparing a sample of the compound in CD3OD with addition of 40 μL of NaOD (40% w/w in D2O) and sonication for 10 min at 40 °C. The NMR spectra (Figures S15−S19 and Table S3, Supporting Information) can be attributed to fully (Ct3−) or partially (Ct2−) unprotonated forms (Scheme S1, Supporting Information). 13C NMR contains a signal at 192.3 ppm and several signals approximately 170−175 ppm corresponding to carbon from CO and respectively from C−O−. The presence of several signal to approximately 170−175 and 131 ppm suggest a mixture of Ct3− and Ct2− forms. The carbon from 180 ppm can be attributed to ethyl acetate in basic condition used on column chromatography (see Supporting Information for more details). Direct pH Jumps. The direct pH jump from an equilibrated solution at pH = 1 to 6.4 followed by stopped flow, is shown in Figure 4. The process is biexponential. At this pH value both cis (minor) and trans-quinoidal (major) bases should be formed during the mixing time of the stopped flow, from the respective flavylium cations (process (i) in Figure 4c). Considering that FL1 is red-shifted in comparison with FL2, it is reasonable to consider that the red-shifted absorption band observed immediately after the pH jump is due to the cisquinoidal base (minor) and that the blue-shifted band corresponds to the trans-quinoidal base (major). The fast disappearance of the cis-quinoidal base without interfering significantly with the disappearance of the trans-quinoidal base leads to the traced line absorption band. This last absorption 5306


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Figure 6. (a) Spectral variations after a reverse pH jump from 12 to 5.1; kobs1 = 0.11 s−1; kobs2 = 0.16 s−1; (b) the same to pH = 1.2; kobs1 = 0.023 s−1; (c) proposed pathways for the reverse pH jump from 12 to 5.1.

The reverse pH jumps to pH = 1.2, Figure 6b, leads immediately to the trans-chalcone that evolves in a few seconds to FL1 in a similar behavior as the one reported in Figure 1. This experimental result indicates that this pathway changes with the pH. Recently, we reported that the trans to cis isomerization is catalyzed by the proton in acidic medium.17 A similar acid catalysis of the cis−trans isomerization is thus expected to occur in the present system, inducing a new pathway as the one in black of Scheme 5. The spectral variations accompanying a direct pH jump from pH = 1.0 to 12.9 are represented in Figure 7. The global process is compatible with formation of the two ionized bases during the mixing time of the stopped flow (as kinetic products) followed by their transformation into the ionized CtCt species.

The ionized bases are obtained during the mixing time of the stopped flow. In flavylium and styrylflavylium compounds the quinoidal bases are kinetic products that retard the formation of the trans-chalcones. The present process is much faster and thus should take place through the spiro intermediate, or through the direct attack of the hydroxyl to the (ionized) quinoidal base. One possible explanation for the biexponential nature of the kinetics is to attribute the faster step to the conversion of the ionized quinoidal base of FL1 and the slowest to the conversion of the ionized quinoidal base of FL2 or directly by hydroxyl attack or upon isomerization through the ionized spiro form.

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CONCLUSIONS Through this work the intimate relation between 2,2′spirobis[chromene] derivatives and anthocyanins was unequiv5307


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The Journal of Organic Chemistry Scheme 5. Possible Pathway for the Formation of FL1, Immediately after a pH Jump from 12 to 1.2

purified by column chromatography using a mixture of hexane:ethyl acetate (5:2) as eluent. Yield: 0.43 g (1.4 mmol) 70%. Anal. Calcd for C20H16O3 (304.35): C, 78.93; H, 5.30. Found: C, 79.18; H, 5.46%. The full assignment of 1H and 13C NMR data for 7,8-dihydro-6Hchromeno[3,2-d]xanthen-2-ol in DMSO-d6 and CD3OD (Bruker AVANCE III 500 MHz spectrometer, 298.0 K, 500 Hz and 125 MHz, respectively) is reported in Table S1 in Supporting Information. Solution Studies. Direct pH jumps were carried out by addition of 1 mL of flavylium cation at pH = 1 to a cuvette (1 cm optical path length) containing 1 mL of 0.1 M NaOH and 1 mL of universal buffer previously adjusted at the desired pH with concentrated HCl. Reverse pH jumps were performed through the addition of HCl to solutions equilibrated or pseudoequilibrated (i.e., before significant formation of trans-chalcone) at slightly acidic or neutral pH values. UV/vis absorption spectra were recorded on a Varian Cary 100 Bio or 5000 spectrophotometer. The stopped-flow experiments were conducted on an Applied Photophysics SX20 stopped-flow spectrometer equipped with a photodiode array detector. Direct pH jumps investigated by stopped-flow were carried out by charging one syringe (6 mL) with flavylium cation solution at pH = 1 and the other syringe with 4 mL of universal buffer at the desired pH and 2 mL of 0.3 M NaOH. The analyzed solutions were recovered and the pH was measured with a glass electrode. Experiments under continuous irradiation were conducted using a xenon lamp (excitation band isolated with a monochromator). The solutions were irradiated in a quartz cuvette (path length = 1 cm) with magnetic stirring. The absorption spectra were registered before irradiation and at selected time points of irradiation period. The incident light intensity was measured by ferrioxalate actinometry.18 All curve-fitting procedures were carried out using the solver program from Microsoft Excel.

Figure 7. Spectral variations after a direct pH jump to 12.9. The process is biexponential with rate constants 1.4 s−1 and 0.07 s−1.

ocally proved. Anthocyanins are ubiquitous in nature and play important roles in food and human health. The fact that 2,2′spirobis[chromene] derivatives are related with anthocyanins opens the possibility of using a bioinspired strategy to produce new compounds and explore their properties in fields where the physical−chemical properties of anthocyanins have been explored. The bridge connecting positions 3 and 3′ of the 2,2′-spirobis[chromene] seems to prevent the formation of isomers exhibiting a different pattern of substitution by one side, but allow the isomerization of the pendent arm of the flavylium cation by the other.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b00634. X-ray crystallography data of FL2 perchlorate salt (CIF) NMR characterization of 7,8-dihydro-6H-chromeno[3,2d]xanthen-2-ol (spiro compound), structural identification of FL1 and FL2 upon full assignment of 1H and 13C NMR spectra under acidic conditions, NMR spectra under basic conditions, and irradiations with cutoff filters (PDF)

EXPERIMENTAL SECTION

Synthesis of 7,8-Dihydro-6H-chromeno[3,2-d]xanthen-2-ol. 2-(2-hydroxybenzylidene)cyclohexanone (0.4 g, 2 mmol) was dissolved into 50 mL of ethanol while stirring. Then 0.28 g (2 mmol) of 2,4-dihydroxybenzaldehyde was added and stirred until total dissolution. Over this mixture, gaseous HCl was gently passed (generated by adding 30 mL of conc. H2SO4 over 20 g of NaCl) for about 1 h. The mixture was then stirred for another 2 h and the reaction was quenched by addition of 30 mL of distilled water. A purple precipitate was isolated by filtration. The spiro form was 5308


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AUTHOR INFORMATION

Corresponding Authors

*[email protected]. *[email protected] ORCID

A. Jorge Parola: 0000-0002-1333-9076 Fernando Pina: 0000-0001-8529-6848 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the Associated Laboratory for Sustainable ChemistryClean Processes and Technologies LAQV-REQUIMTE. The latter is financed by national funds from FCT/MEC (UID/QUI/50006/2013) and cofinanced by the ERD under the PT2020 Partnership Agreement (POCI-010145-FEDER-007265). FCT/MEC is also acknowledged through the National Portuguese NMR Network RECI/BBBBQB/0230/2012, A.M. gratefully acknowledges a postdoctoral grant from FCT/MEC SFRH/BPD/69210/2010. The Romanian ICT is also acknowledged for the financial support of the Romanian Academy, Project 4.1 and Prof. S. Shova is acknowledged for the infrastructure used in this work through POSCCE-O 2.2.1, SMIS-CSNR 13984-901, No. 257/ 28.09.2010 Project, CERNESIM.

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REFERENCES

(1) Flavonoids, Chemistry, Biochemistry and Applications; Andersen, Ø.; Markham, K. R., Eds.; Taylors & Francis: N. Y, 2006. (2) Pina, F.; Melo, M. J.; Laia, C. A. T.; Parola, A. J.; Lima, J. C. Chem. Soc. Rev. 2012, 41, 869−908. (3) Brouillard, R.; Lang, J. Can. J. Chem. 1990, 68, 755−761. (4) McClelland, R. A.; Gedge, S. J. Am. Chem. Soc. 1980, 102, 5838− 5848. (5) Brouillard, R.; Dubois, J.-E. J. Am. Chem. Soc. 1977, 99, 1359− 1364. (6) Petrov, V.; Parola, A. J.; Pina, F. J. Phys. Chem. A 2012, 116, 8107−8118. (7) Pina, F.; Parola, J.; Gomes, R.; Maestri, M.; Balzani, V. Molecular Switches, 2nd ed.; Feringa, B. L., Browne, W. R., Eds.; Wiley-VCH: Weinheim, 2011; Vol. 1, Ch. 6, pp 181−226. (8) Andreasson, J.; Pischel, U. Chem. Soc. Rev. 2010, 39, 174−188. (9) Mattia, E.; Otto, S. Nat. Nanotechnol. 2015, 10, 111−119. (10) Chen, X.; Wang, S. Synlett 2015, 26, 2042−2046. (11) McCurdy, A.; Kawaoka, A. M.; Thai, H.; Yoon, S. C. Tetrahedron Lett. 2001, 42, 7763−7766. (12) Salama, T. A.; Ismail, M. A.; Khalil, A.-G. M.; Elmorsy, S. S. Arkivoc 2012, No. ix, 424−253. (13) Lu, N. T.; Nguyen, N.; McCurdy, A.; Kumar, S. J. Org. Chem. 2005, 70, 9067−9070. (14) Sugden, S.; Wilkins, H. J. Chem. Soc. 1927, 0, 139−147. (15) Karrer, P.; Fatzer, W. Helv. Chim. Acta 1942, 25, 1138−1142. (16) Moro, A. J.; Pana, A.-M.; Cseh, L.; Costisor, O.; Parola, A. J.; Cunha-Silva, L.; Puttreddy, R.; Rissanen, K.; Pina, F. J. Phys. Chem. A 2014, 118, 6208−6215. (17) Avó, J.; Petrov, V.; Basílio, N.; Parola, A. J.; Pina, F. Dyes Pigm. 2016, 135, 86−93. (18) Hatchard, C. G.; Parker, C. A. Proc. R. Soc. London, Ser. A 1956, 235, 518−536.

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