KetoâEnol Tautomerism of Phenindione and Its ... - ACS Publications

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Keto−Enol Tautomerism of Phenindione and Its Derivatives: An NMR and Density Functional Theory (DFT) Reinvestigation Mark V. Sigalov* Department of Chemistry, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 8410501, Israel S Supporting Information *

ABSTRACT: Keto−enol tautomerism of phenindione (2-phenyl-1,3-indandione) and of its 4-phenyl-substituted derivatives was reinvestigated by NMR, supported by density functional theory (DFT) quantum-mechanical calculations. The calculated data quantitatively confirmed the stabilization in DMSO solution of the enol form by a strong hydrogen bond. The symmetry of the NMR spectra of the enol forms was explained by a fast proton transfer between carbonyl oxygen atoms, which is facilitated by the formation of a strong ionic complex of the enol form and an anion. It was shown that keto−enol tautomerization also proceeds with the participation of a similar complex between an anion and the diketo form of 2-phenyl-1,3-indandione.

spectroscopy methods, and very little work has been done using NMR spectroscopy. Among the few studies that have been performed, a 13C NMR study of phenindione showed that 95% of the molecules exist as diketones in chloroform, whereas 75− 80% of the molecules are enolized in DMSO.17 In that study, 1 H NMR spectral patterns were not discussed, except for mentioning that the signals were “broad and poorly resolved”. Moreover, the significant characteristic signal of the hydrogenbonded OH was not observed, probably because lowtemperature spectra in other polar solvents were not recorded. This issue is very important because the driving force for enol formation in solution is generally accepted to be H-bond formation between enolic OH groups and solvent molecules.18 H bonds are usually postulated to be present in the solid state. According to X-ray data, in the black crystals of 2-[4(dimethylamino)phenyl]-1,3-indanedione the enol form coexists with the zwitterionic form of the molecule and these two tautomers are stabilized and bonded to each other by strong ionic O−···H···O hydrogen bonds (the O···O distance is 2.53 Å). In the case of derivative 3a (Scheme 1), despite the conclusion that the compound exists in the enol form, splitting of the protons of the naphthalene moiety in the 1H NMR spectrum was symmetrical.19 To explain this contradiction, the authors suggested that a fast 1,5-sigmatropic rearrangement occurs in this molecule, such that the acidic proton is transferred from one oxygen atom onto another. This very unlikely hypothesis was not employed later to explain the symmetrical 1H NMR spectrum of dimedone; rather, the formation of dimers (analogous to the acetic acid dimers,

Cyclic 1,3-diketones constitute an important class of organic compounds. Within this class, a major subclass comprises derivatives containing aromatic rings, such as 1,3-indandiones (1). These derivatives 1 (Scheme 1) have been known for more than a century1 and found numerous applications as drugs (anticoagulants, analgesics, anti-inflammatory medicines),2 reagents in analytical and forensic chemistry (ninhydrins),3 dyes (including near-infrared dyes) and pigments,4−7 semiconductors and photosemiconductors,8 and components of advanced materials.9−13 Overall, about 3000 relevant papers have been published since Hantzsch proposed, in 1913, the enol 1a to be the predominant form of phenindione (2-phenyl1,3-indandione 1, R = Ph) in polar solvents.14 On the other hand, the correct structures of the products of the simplest reaction of 1 (R = H)self-condensationwere established just recently.15 Despite ongoing interest in derivatives 1, only about 20 publications have related to derivatives 2; those publications, which are mostly patents, were published between 1957 and 2013. One of the most intriguing properties of 1, especially of those with R = Ar, is their polychromism in the solid state:16 the color of these compounds, depending on the solvent used for crystallization and the substituents on the Ar and phthaloyl rings, can vary from colorless to deep green. It is noteworthy that the colored forms often possess considerable electrical conductivity whose origin is not clear.8 It has been shown that the diketo forms 1 are colorless crystals, whereas the color of the highly colored compounds may be attributed to the formation of the enol forms 1a. It is currently accepted that most of the substituted colored 2-aryl-1,3-indandiones exist as enols. Reports concerning keto−enol equilibrium in 1,3-indandiones are based on the use of infrared and ultraviolet © XXXX American Chemical Society

Received: December 15, 2014 Revised: January 28, 2015

A

DOI: 10.1021/jp512461c J. Phys. Chem. A XXXX, XXX, XXX−XXX

Article

The Journal of Physical Chemistry A Scheme 1. 1,3-Indandione (1, R = H) and Its Analogs

Scheme 2. Postulated Intermolecular Proton Exchange in Dimedone Dimers

Scheme 3. Compounds Studied in This Work

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Scheme 2) with fast intermolecular proton exchange was offered as the explanation.20 However, in light of the steric interactions between the two C−H hydrogen atoms in the coplanar structure of the dimer, the above explanation, too, is rather doubtful, particularly since 2-aryl derivatives of 1,3-indandione also found to give symmetrical NMR spectra. This finding was one of the factors that encouraged undertaking this study. The present article reports the results of a detailed investigation of keto−enol tautomerism of 2-phenyl-1,3-indandione (4, Scheme 3), its 4′substituted derivatives (5 and 6), and its structural analog 1Hcyclopenta[b]naphthalene-1,3(2H)-dione (7) by NMR spectroscopy, supported by quantum mechanical, namely, density function theory (DFT) calculations. The calculations were applied also to the parent unsubstituted 1,3-indandione 1 (R = H) for the sake of comparison.

RESULTS AND DISCUSSION

NMR Spectra. In agreement with ref 17, the 1H NMR spectrum of 2-phenyl-1,3-indandione (4) in CDCl3 (Figure 1a) corresponds to 100% of the diketo tautomer, whereas the spectrum recorded in DMSO-d6 (Figure 1b) contains the broad signals of two compounds, with the content of the major compound being about 80%. The assignment of the peaks also corresponds to that given in ref 17. More specifically, the signals at 7.43 and 7.49 ppm (in DMSO-d6) may be assigned to the phthaloyl ring protons, the doublet at 7.88 ppm and the triplets at 7.37 and 7.20 ppm to the phenyl ring protons of the major compound, and the signals at 8.04 and 7.13 ppm (other signals overlap) to the phthaloyl ring protons and to the 4-H of the phenyl ring, respectively, of the minor component. These broad signals indicate an exchange process that is characterized by a moderate to fast rate on an NMR time scale. It is worth noting that solutions of 4 and of its analogs 5 and 6 are colorless or yellowish when the compounds are dissolved in B


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The Journal of Physical Chemistry A

Figure 1. Aromatic parts of the 1H NMR spectra of 4 in CDCl3 (a) and DMSO-d6 (b).

Figure 2. Aromatic part of the 2D NOESY spectrum for 4 in DMSO-d6 (cross-peaks are highlighted by red circles and correspond to similar protons in the exchanging components; see text for details).

Experimental evidence of a slow dynamic process was obtained from the 2D NOESY NMR spectrum of 4 in DMSO (Figure 2). This experiment unambiguously proves the chemical exchange between phthaloyl and phenyl protons of

CDCl3 or CD2Cl2 but dark red in DMSO solution. In contrast, the unsubstituted 1,3-indandione 1 does not show a change of color or a change in the NMR spectrum when it is dissolved in different solvents. C


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Figure 3. Aromatic parts of the 1H NMR spectra of 5 in the DMSO-d6/CD2Cl2 (1:1) mixture at (a) 290, (b) 260, (c) 240, and (d) 180 K.

methoxy derivative 5 in a mixture of DMSO and dichloromethane-d2 are evident in the spectra shown in Figure 3. At 290 K, the spectrum is more resolved and the concentration of the diketo form is higher (amounts about to 50%) than that in pure DMSO-d6. As can be seen in Figure 3, at low temperatures the symmetry of the spectrum becomes broken: the low-field multiplet of the indandione aromatic cycle at 7.3 ppm is well resolved at 290 K (Figure 3a), broadens at 260 K (Figure 3b), and then decoalesces at 240 K (Figure 3c) and at lower temperatures splits into two signals (Figure 3d). Simultaneously, the concentration of the diketo compound decreases and reaches 20% at 180 K. In addition, at 220 K a broad signal of the enol OH group (δ = 12.9 ppm) appears; this signal narrows at lower temperatures (inset, Figure 3d). The observation of an OH signal proves the structure of the enol form. These changes are reversible, as subsequent heating of the sample restores the original spectrum. Compound 4 undergoes similar changes with temperature. As mentioned above, in DMSO the p-nitro-substituted compound 6 consists solely of the enol component. Moreover, its spectrum in the mixture of solvents does not reveal any changes with temperature, and no OH signal appears, even at 180 K. The observed dynamic process that is related to the symmetry of the 1H and 13C NMR spectra in DMSO-d6 may be explained by interconversion of two equivalent enol forms due to proton exchange between the carbonyl oxygen atoms O-1

the major and minor components in equilibrium. Thus, the broad signal at 8.1 ppm, which belongs to the phthaloyl protons of the minor compound, has two cross-peaks with broadened signals (at 7.43 and 7.49 ppm) that are related to the similar protons of the major component; the doublet of phenyl ortho protons of the major component has cross-peaks with broad signal of low-intensity at 7.13 ppm of the minor species, whereas the two triplets at 7.37 and 7.20 ppm have cross-peaks between each other, confirming their assignment to the meta protons of the phenyl ring of both components. Other derivatives (5−7) show similar behavior in the two solvents, namely, 100% diketo form in CDCl3 and the presence of two species in equilibrium in DMSO-d6. The differences between derivatives 5 and 6 lie in the concentrations of the second component, which amount to 70% for 5 and 100% for 6 (for evaluation of the substituent dependence of this equilibrium, the same concentrations of the studied compounds (0.02 M) were taken). Compound 7 differs from the other two in that the concentration of the second component amounts to only 30%. It is worth noting that, in these experiments at ambient temperatures, the signal of the enolic OH was not observed. Recently, we have shown that these signals do become visible at low temperatures.21 For the measurements below the melting point of DMSO (290 K), dichloromethane-d2 was used as a cosolvent, which allowed the samples to be cooled from 290 K down to 180 K. The changes in the 1H NMR spectrum of the D


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Figure 4. 1H NMR spectra of the 2:1 mixture of (4) and its TBA salt in CDCl3 at (a) 295 and (b) 260 K. Nonoverlapping signals of the salt protons are marked with asterisks.

Figure 5. 1H NMR spectra in DMSO-d6: (a) pure 4, (b and c) first and second addition of the TBA salt of 4, and (d) pure TBA salt.

E


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Figure 6. 1H NMR spectra of 4 in DMSO-d6/CD2Cl2 at 200 K: (a) without and (b) with the addition of 0.02 equiv of the TBA salt.

their position in the spectrum of the pure salt in DMSO (Figure 5d), whereas the signals of the diketo form broaden and diminish but remain in the same place. Figure 6 shows the spectra of 4 recorded at 200 K in the absence (Figure 6a) or presence (Figure 6b) of a small amount of TBA salt. The following changes in the spectrum are caused by addition of the TBA salt: the signal of the indandione aromatic cycle at 7.3 ppm narrows; the OH signal becomes visible only at 180 K and is shifted to low field by 0.33 ppm relative to the measurement without salt addition (see below). These findings indicate that the enol−enol interconversion becomes much faster in the presence of the TBA salt, implying that the anion participates in this equilibrium as a catalyst. The reason for this catalytic activity may be the formation of an ionic complex between the enol and the anion, stabilized by a strong O−H···O− hydrogen bond. Fast proton transfer between oxygen atoms results in average spectra; this phenomenon explains the behavior of the enol signals in Figure 5b and 5c. The protons participating in the ionic hydrogen bond are characterized by a large 1H NMR chemical shift at 17−22 ppm. 23−28 Therefore, the increase in concentration of this complex in response to salt addition shifts the average OH signal toward a lower field. In contrast, the absence of significant spectral changes (except for slight broadening) with the addition of a TBA salt to the chloroform solution of 4 suggests that the diketo tautomer does not form a stable complex with the anion. Theoretical Calculations. Quantum mechanics (DFT) calculations were carried out to explain the NMR spectral behavior and evaluate the relative stability of the tautomeric

and O-3. The rate of exchange depends strongly on the ring substituents, being the highest in 6. From the temperature-dependent 1H NMR spectra of 4 (see Experimental and Calculation Details), the energy of activation of the exchange process at the coalescence temperature was estimated to be 9.6 kcal/mol. 2-Phenyl-1,3-indandione 4 is a C−H acid of moderate strength (pKa = 4.0922), implying the presence of considerable amounts of its anion in polar solvents, such as water, ethanol, or DMSO. The experimental evidence of this ionization was obtained by measuring the electric conductivity of a 0.1 M solution of 4 in DMSO as follows: molar conductivities (λ = χ/ 0.1) are Ph-indandione in DMSO 0.435 mS, Ph-indandione tetrabutyl ammonium (TBA) salt in DMSO 4.90 mS, and neat DMSO 0.35 μS. From these values one can conclude that approximately 9% of the compound was ionized. It is worth noting that the percentage of an anion in a solution will depend on the solute concentration and the polarity of the solvent. In particular, the mixture DMSO-d6/CD2Cl2 is less polar than neat DMSO, and therefore, the anion content in such a mixture will be even lower than that in DMSO. The role of anion in the keto−enol tautomerization and in the enol−enol interconversion may be revealed by the variation of its content in solution. The 1H NMR spectrum of a mixture of 4 and its TBA salt in CDCl3 at room temperature comprises the superposition of two separate spectra, but with slightly broadened signals (Figure 4a), which narrow at 260 K (Figure 4b). In contrast, when the TBA salt is added to a DMSO solution of 4 (Figure 5a−c), no new signals appear in the spectrum. Instead, the signals belonging to the enol form broaden and move toward F


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Table 1. Total Energies, Etotal, Zero-Point Corrected Total Energies, EZP, Free Energies of Complexation, G°, and Their Differences for Diketo-DMSO and Enol-DMSO Complexes Etotal, au (ΔE, kcal/mol)a DMSO 1 diketo complex enol complex 4 diketo complex complex enol complex complex

−1281.5411 −1281.5457 (1.7)

1:1 1:2

−1281.5411

1:1 1:2

−1281.5457

EZP, au

G°, au

−553.1945

−553.2228

−497.0305 −1050.23 −497.0127 −1050.2268

−497.064 −1050.2765 −497.0456 −1050.2725

−728.0538 −1281.2533 −1834.4534 −728.041 −1281.2583 −1834.4574

−728.0949 −1281.3073 −1834.5196 −728.0829 −1281.3094 1834.5209

−842.5770 −1395.7772 −842.5672 −1395.7815

−842.6225 −1395.8341 −842.6109 −1395.8375

−932.6112 −1485.8122 −932.6039 −1485.8207

−932.6570 −1485.8678 −932.649 −1485.8766

−650.6616 −1203.8611 −650.648 −1203.862

−650.6986 −1203.9104 −650.6845 −1203.910

ΔEZP, kcal/mol

ΔG°, kcal/mol

−3.1

6.5

−12.3

−2.6

−3.1 −6.6

6.5 13.1

−14.3 −17.2

−2.3 4.7

−3.6

7.0

−12.6

−2.4

−4.1

7.5

−14.0

−3.0

−3.1

6.9

−12.2

−1.7

(−2.9) 5 diketo complex 1:1 enol complex 1:1

a

−1396.0964 −1396.1008 (−2.8)

6 diketo complex enol complex

−1486.1016

7 diketo complex enol complex

−1204.1139

−1486.1102 (−5.4)

−1204.1154 (−0.9)

ΔE = Etotal(enol-DMSO) − Etotal(diketo-DMSO).

energies EZP, free energies of complexation G°, and their differences for diketo-DMSO and enol-DMSO complexes). In general, the experimental ratio of the enol form to the diketo form in DMSO is in agreement with calculated ΔEtotal values (Table 1). In addition, the complexes of the diketo form with DMSO, according to the positive values of their free energies, are not stable at room temperature. Thus, these calculated data confirm quantitatively the notion of enol stabilization by a hydrogen bond. It is worth noting that inclusion of a second solvent molecule results in a decrease of stabilization energy for both the diketo-DMSO complex and the enol-DMSO complex (Table 1). It is known29−31 that self-tautomerization of β-diketones to keto−enols via intramolecular proton transfer from carbon to oxygen is unfavorable due to a very high energetic barrier (up to 65 kcal/mol). Recently, it was shown32 that for 1,3-cyclohexanedione the formation of C−H···O hydrogen-bonded dimers of a diketo tautomer facilitates intermolecular proton transfer, thereby lowering the tautomerization barrier to 35−45 kcal/mol. The formation of a similar complex may be possible for unsubstituted 1,3-indandione 1 and for the naphthyl derivative 7, but it is sterically prohibited for 2-aryl derivatives 4-6.

forms of 2-aryl-1,3-indandiones and their complexes with solvent molecules and anions. Relative Stability of Tautomers and Their Complexes with DMSO. The parent unsubstituted 1,3-indandione molecule 1 is predicted to exist exclusively in the diketo form, which is lower in energy, namely, by 13.7 kcal/mol, than the enol form in the gas phase. This difference for optimization of 1 in DMSO as a solvent [polarizable continuum model (PCM)] decreases to 11.8 kcal/mol. Moreover, the complex of the diketo form of unsubstituted 1 with DMSO is still more stable (by 1.7 kcal/ mol) than the enol−DMSO complex. These data are in perfect agreement with the absence of color of the DMSO solution and with the 1H NMR experiment. Introduction of the 2-phenyl substituent decreases the energy gap between the tautomers, although the diketo tautomer of 4 is still more stable than its enol counterpart, both in the gas phase and in DMSO as a solvent (PCM) (by 6.5 and 5.7 kcal/mol, respectively). However, the complexation of the tautomers with one DMSO molecule in DMSO solution (PCM-SM model), both for 4 and for the other compounds 5−7, gives the reverse order of stability, i.e., the O−H···OS hydrogen-bonded complex of the enol form with DMSO becomes more stable than the C2− H···OS hydrogen-bonded diketo form−DMSO complex (see Table 1 for total energies Etotal, zero-point corrected total G


Article

The Journal of Physical Chemistry A Scheme 4. Complexes of Diketo and Enol Forms of 4 with Its Anion

symmetrical appearance of the 1H NMR spectra of enol tautomers. It should be noted that, in the case of proton exchange between two oxygen atoms, the starting and final species are identical, whereas the staring and final species for keto−enol tautomerization are not. The reaction pathways and transition states for both proton transfer processes were calculated for the example of compound 4 (Scheme 5). At first glance, the calculated energy of the transition state for enol-anion proton transfer (1.1 kcal/mol) is quite different from the experimental value of the above-mentioned enol−enol interconversion (9.6 kcal/mol). However, two points should be taken into account: (1) according to electrical conductivity measurements, the anion concentration in pure DMSO does not exceed 9%, and in the mixture DMSO-d6/ CD2Cl2 used for low-temperature measurements the concentration of the anion is even lower; (2) the enol tautomer forms rather strong complexes with DMSO, and their dissociation before subsequent complexation with the anion requires considerable additional energy. Thus, in light of these two factors the experimentally estimated energy of the enol−enol interconversion must be higher than the calculated energy. Similar considerations related to anion concentration are also relevant for diketo-anion complexes, i.e., the observed rate of the keto− enol tautomerization will be slower than that expected from the energy of the tautomerization transition state. Nevertheless, this energy is much lower than in the case of cyclohexanedione diketo dimers mentioned above.32 Experimental and Calculation Details. Compounds 4 and 6 were purchased from Aldrich and used without purification. The synthesis of compounds 5 and 7 was carried out according to previously described procedures.33,34 1H NMR spectra were recorded on a Bruker DMX-500 spectrometer at working frequencies of 500.13 (1H) MHz; 1H NMR chemical shifts are reported in parts per million relative to TMS.

As mentioned above, the dynamic behavior of the studied compounds in DMSO solution indicates the participation of anions in the exchange process. The addition of the TBA salt (Figure 4) leads to the following changes: (1) decrease in the concentration of the diketo form, i.e., facilitation of its transformation to a keto−enol tautomer, and (2) increase in the rate of proton exchange between its oxygen atoms. These features may easily be explained by the formation of two complexesan anion-diketo form and an anion-enol form. The DFT calculations show that the energy required for these transformations allows their observation at ambient or low temperatures. The optimized geometry of the complexes formed by an anion of 2-phenyl-1,3-indandione with the diketo and keto− enol forms is shown in Scheme 4. The first complex is stabilized by two C−H···O hydrogen bonds, with r(O···H) distances of 2.136 and 2.526 Å. The bond C2−H that participates in the hydrogen bond is elongated in the complex by 0.005 Å (1.103 Å, as compared with 1.098 Å in a diketone molecule). The second complex possesses a strong O−H···O bond (r(O···H) = 1.446 Å) According to the values of the total energy (Table 2), the enol-anion complexes are more stable than their diketo counterparts. The same conclusion follows from the consideration of their ZP-corrected energy and free energy of complexation ΔG°. The latter parameter has positive values for diketo complexes, indicating that, despite some ease of formation, diketo complexes are unstable at ambient temperatures. There are two ways in which the transformation of these complexes can take place: (a) a simple dissociation of the starting components and (b) a proton transfer from C-2 of the diketo form to a carbonyl oxygen of the anion, i.e., a diketo to keto−enol tautomerization. However, the existence of the strong hydrogen bond in the enol-anion complex implies a low barrier for the proton exchange between two oxygen atoms. As it was postulated above, this process is responsible for the H


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Table 2. Total Energies, Etotal, Zero-Point Corrected Total Energies, EZP, Free Energies of Complexation, G°, and Their Differences (ΔE) for Diketo-Anion and Enol-Anion Complexes Etotal, au (ΔE, kcal/mol)a 1 anion diketo complex enol complex 4 anion diketo complex enol complex 5 anion diketo complex enol complex 6 anion diketo complex enol complex 7 anion diketo complex enol complex a

EZP, au

G°, au

−496.5645 −497.0305

−496.5973 −497.0640

−497.0127 −993.5994

−497.0456 −993.6487

−727.5967 −728.0538 −1455.6634 −728.041 −1455.6670

−727.6360 −728.0949 −1455.7282 −728.0829 −1455.7338

−842.1257 −842.577 −1684.7082 −842.5672 −1684.7147

−842.1688 −842.6225 −1684.7783 −842.6109 −1684.7842

−932.1734 −932.6112 −1864.7904 −932.6039 −1864.7986

−932.2171 −932.6570 −1864.8620 −932.649 −1864.8703

−650.20 −650.6616

−650.236 −650.6986

650.648 −1300.8723

−650.6845 −1300.929

−993.8397 −993.8395 (0.1)

−1456.0654 −1456.0716 (−3.9)

−1685.1743 −1685.1810 (−4.2)

−1865.1969 −1865.2053 (−5.3)

−1301.1994 −1301.2056 (−3.9)

ΔEZP (kcal/mol)

ΔG° (kcal/mol)

−2.9

6.1

−13.9

−3.6

−8.1

1.7

−18.4

−9.3

−3.4

8.2

−13.7

−2.8

−8.8

2.4

−13.4

−2.6

−2.9

6.1

−15.2

−5.3

ΔE = Etotal(enol-anion) − Etotal(diketo-anion)

unsubstituted 1,3-indandione is the diketo form independent of the solvent, whereas keto−enol equilibrium in 2-phenyl-1,3indandione, its 4′-substituted derivatives, and its benzo-analog 1H-cyclopenta[b]naphthalene-1,3(2H)-dione was mainly governed by solvent properties. In CDCl3 all these compounds exist exclusively in the diketo form. The predominant tautomer for these compounds in DMSO solution is the keto−enol form. The nature of substituents plays a minor role, i.e., the content of enol increases in the order 4-MeO (70%) < H (80%) < 4NO2 (100%). The shift of equilibrium toward enol form in 2aryl-1,3-indandione derivatives with increasing medium polarity was explained by the formation of a hydrogen bond with the solvent molecules and confirmed quantitatively by DFT quantum-mechanical calculations. The measurements of electrical conductivity show a considerable extent of ionization of 2-phenyl-1,3-indandione in DMSO. The 1H NMR spectrum of the mixture of 2-phenyl1,3-indandione with its TBA salt in the solvent of low polarity (CDCl3, CD2Cl2) represents the superposition of the spectra of separate components indicating that interaction between them is negligible. On the contrary, in DMSO-d6 1H NMR shows the fast intermolecular proton exchange between the enol form and

Electrical conductivity was measured on a TH2300 conductometer. The energy of activation for intramolecular proton transfer was estimated at the coalescence temperature (250 K) using the Eyring equation ΔG⧧ = 4.57Tc{9.97 + log(Tc/Δν)}

Geometry optimization for compounds 4−7 and for their anions and complexes was performed by applying DFT using the B3LYP potential and 6-311g(d,p) basis set in the gas phase and in DMSO solution (IEFPCM model). No restrictions were imposed on the geometry optimization. All calculated minima were verified by frequency calculations; no imaginary frequencies were found, whereas all transition states were characterized by one strong imaginary frequency. Transition states were calculated by Berny optimization on the B3LYP/6311g(d,p) level. All computations were performed with the Gaussian 09 program package.35

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CONCLUSION Experimentally (NMR spectroscopy) and theoretically (DFT calculations) it was found that the most stable tautomer of I


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Scheme 5. Geometry and Energy of Transition States for (a) Keto−Enol Tautomerization and (b) Enol−Enol Proton Exchange

(7) Oparin, D.; Khodorkovsky, V. Synthesis of 1-H-Thiophthalylium Salts and their Electrophilic Characteristics. J. Org. Chem.USSR 1993, 29, 168−178. (8) Silins, E.; Taure, L. Mechanism of Charge Carrier Generation in Thin Layers of Molecular Associates. Phys. Status Solidi 1969, 32, 847−852. (9) Meshulam, G.; Berkovic, G.; Kotler, Z.; Ben-Asuly, A.; Mazor, R.; Shapiro, L.; Khodorkovsky, V. Measurement of the Second Order Optical Nonlinearity of 1-Dimensional and 2-Dimensional Organic Molecules. Ann. Isr. Phys.Soc. 2000, 14 (Electro-Optics and Microelectronics), 71−74. (10) Schwartz, H.; Mazor, R.; Khodorkovsky, V.; Shapiro, L.; Klug, J. T.; Kovalev, E.; Meshulam, G.; Berkovic, G.; Kotler, Z.; Efrima, S. Langmuir and Langmuir-Blodgett Films of NLO Active 2-(p-N-AlkylN-methylamino)benzylidene-1,3-indandione-p/A Curves, UV-Vis Spectra, and SHG Behavior. J. Phys. Chem. B 2001, 105, 5914−5921. (11) Gvishi, R.; Berkovic, G.; Kotler, Z.; Krief, P.; Becker, J. Y.; Sigalov, M.; Shapiro, L.; Khodorkovsky, V. New Two-Photon Fluorescent probe for Multiphoton Microscopy in Biological Media. Proc. SPIE-Int. Soc. Opt. Eng. 2003, 5036 (Photonics, Devices, and Systems II), 437−442. (12) Gvishi, R.; Berkovic, G.; Kotler, Z.; Krief, P.; Shapiro, L.; Klug, J. T.; Skorka, J.; Khodorkovsky, V. Studies of NewTwo-Photon Fluorescent Probes Suitable for Multiphoton Microscopy in Biological Settings. Proc. SPIE-Int. Soc. Opt. Eng. 2003, 5211 (NonlinearOptical Transmission and Multiphoton Processes in Organics), 82−90. (13) Acharya, S.; Krief, P.; Khodorkovsky, V.; Kotler, Z.; Berkovic, G.; Klug, J. T.; Efrima, S. Studies of Langmuir and Langmuir-Blodgett films of NLO-active Amphiphilic 1,3-Indanedione Derivatives. New J. Chem. 2005, 29, 1049−1057. (14) Hantzsch, A. Ü ber die Keto-Enol-Isomerie der Indandione und Oxindone Derivate. Justus Liebigs Annalen der Chemie 1913, 392, 286− 347. (15) Jacob, K.; Sigalov, M.; Becker, J. Y.; Ellern, A.; Khodorkovsky, V. Self-condensation of 1,3-Indandione: a Reinvestigation. Eur. J. Org. Chem. 2000, 2047−2055. (16) Neilands, O.; Balodis, K.; Kacens, J.; Kreicberga, J.; Medne, R.; Paulins, L.; Pukitis, G.; Khodorkovskii, V.; Edzina, A. From Deepcolored 2-Aryl-1,3-indandiones to Strong Electron Donors and Organic Superconductors. Latvijas PSR Zinatnu Akademijas Vestis, Kimijas Serija 1986, 64−79.

the anion. Lowering temperature results in slowing down of this exchange. The DFT calculations show that formation of a strong hydrogen-bonded complex between the anion and the enol form is responsible for the symmetry of 1H NMR spectra of studied compounds in DMSO and that the formation of similar complex between the anion and the diketo form facilitates the transformation of the diketo to the keto−enol tautomer.

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ASSOCIATED CONTENT

S Supporting Information *

Cartesian coordinates and total energies of tautomeric forms of compounds 1 and 4−7 and transition states for proton transfer in the complexes 4-diketo-anion and 4-enol-anion. This material is available free of charge via the Internet at http:// pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*Phone: 972-8-6479322. E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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