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Protonation of ninhydrin and indan-1,2,3-trione revisited: A combined theoretical and experimental study
Journal of Molecular Structure 1134 (2017) 1e5
Contents lists available at ScienceDirect
Journal of Molecular Structure journal homepage: http://www.elsevier.com/locate/molstruc
Protonation of ninhydrin and indan-1,2,3-trione revisited: A combined theoretical and experimental study George E. Salnikov a, b, Alexander M. Genaev a, *, Andrey V. Shernyukov a, Vyacheslav G. Shubin a a b
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Academician Lavrent'ev Ave. 9, Novosibirsk 630090, Russian Federation Novosibirsk State University, Pirogova St. 2, Novosibirsk, 630090, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history: Received 18 July 2016 Received in revised form 21 December 2016 Accepted 22 December 2016 Available online 23 December 2016
The literature data on protonation of indan-1,2,3-trione and ninhydrin (indantrione hydrate) in acidic media are inconsistent, formation of dications at pH 3 and very low extent of protonation in superacid CF3SO3H were claimed. Our combined theoretical (DFT, MP2, CCSD) and experimental (NMR) study has shown that indantrione undergoes single protonation in CF3SO3H resulting in monocation formation. In more strong superacid FSO3H-SbF5 dication is formed, but, contrary to the literary data, trication is not formed even in this superacid. Significant dependence of 13C NMR chemical shifts of indantrione on media acidity allows using this compound as a convenient indicator of acidity in a broad range, from H0 3 to 25. © 2016 Elsevier B.V. All rights reserved.
Keywords: Ninhydrin Superacid NMR Quantum chemistry calculations
1. Introduction Carbocation chemistry has been a hot research area for many years [1]. Among carbocations multiply charged cations as superelectrophilic species are of particular interest [2], they are capable to interact with weak nucleophiles. Acid-catalyzed condensation of ninhydrin with aromatic compounds [3e6] is a typical example. Data on structure of protonated forms of ninhydrin 1 and indan1,2,3-trione 2 (dehydrated ninhydrin, Scheme 1) are necessary for understanding the mechanism of these reactions. However, the available data on the matter are not certain. The authors of paper [7] interpreted data of 1H and 13C NMR spectroscopy obtained for solution of ninhydrin in superacid FSO3H-SbF5 as indicating the formation of trication 3 (Scheme 2), and according to authors' of article [8] assumption dication 4 can be formed even in weakly acidic solutions at pH 3. Recently indantrione 2 protonation was studied theoretically on the basis of approach described earlier [9]. It was found that protonation proceeds mainly on the oxygen atoms of the carbonyl groups 1 and 3 sequentially leading to monocation 5 and dication 4 [10]. On the other hand, the data presented in this work predict that in superacid CF3SO3H indantrione 2 must exist
* Corresponding author. E-mail address: [email protected] (A.M. Genaev). http://dx.doi.org/10.1016/j.molstruc.2016.12.057 0022-2860/© 2016 Elsevier B.V. All rights reserved.
mainly in nonprotonated form. To clarify the situation we have studied protonation of ninhydrin and indantrione in a broad range of acids, from CF3COOH to superacids. 2. Results and discussion 2.1. Ninhydrin and indan-1,2,3-trione in FSO3H-SbF5 The 1H NMR data show that nynhydrin 1 in FSO3H-SbF5/SO2ClF/ CD2Cl2 at low temperatures undergoes protonation resulting in dication 6 formation (Scheme 3, SI, supporting information, p. S2). Indicative are the two signals of the geminal hydroxy groups in the region between 5.5 and 6.0 ppm and the three signals of the protonated carbonyl groups in the region between 15.5 and 16.5 ppm (Fig. 1). According to quantum chemical calculations by DFT и MP2 methods (SI, p. S4) the most stable structures of dication 6 are EZ and ZZ conformers, their interconversion being slowed down. Upon increasing the temperature to 80 C dehydration occurs (Scheme 4), confirmed by increase of H3Oþ signal intensity. In 1H NMR spectrum of the particle formed (Fig. 2, SI, p. S5) at 100 C a signal of the protonated carbonyl groups at d 16.1 ppm is observed. 13 C NMR data (Table 1) show that the same particle is formed from ninhydrin 1 and indantrione 2 in FSO3H-SbF5 at room temperature. This particle was observed by the authors of [7] in FSO3H-SbF5/SO2 at 70 C, but the signal of protonated carbonyl groups in 1H NMR
2
G.E. Salnikov et al. / Journal of Molecular Structure 1134 (2017) 1e5
Scheme 1. Reversible dehydration of ninhydrin.
Scheme 2. Protonation of indan-1,2,3-trione.
spectrum was not detected obviously due to a rapid exchange with acidic medium. Indeed, we have found that upon increasing the temperature this signal broadens, almost merging at 80 C with base line (SI, p. S5). The authors of [7] came to conclusion that indantrione 2 undergoes triple protonation in FSO3H-SbF5/SO2 and the trication formed can be considered either a 5C-2p or a 9C-6p bridged Huckeloid system (Scheme 5). Aromatic stabilization is expected to facilitate triple protonation. Indeed, NICS calculations (Fig. 3) show that trication 3 is aromatic. However, DFT/PBE, MP2 and CCSD calculations (gas phase) indicate very low probability of trication 3 formation from dication 4 due to negative proton affinity of the latter (Fig. 3). PBE0/aug-ccpvtz calculations [10] show that the formation of trication 3 is also unfavorable in solution: the Gibbs free energy of dication 4 protonation in TfOH is 35.5 kcal/mol. It is natural to expect that protonation of indantrione 2 in FSO3H-SbF5 should lead to formation of dication 4, not trication 3. The experimental data we have obtained support this suggestion: only one signal in region of the protonated carbonyl groups in 1H NMR spectra at low temperatures is observed (Fig. 2), the intensity of this signal corresponds to 2H, as the most stable conformer of dication 4 has C2v symmetry (Fig. 3) while in case of trication 3 formation appearance of three low-field signals of equal intensity (1H each) would be expected. 13C NMR chemical shifts of indantrione 2 in FSO3H-SbF5 are in a good accordance with the calculated ones for dication 4 and do not correspond to trication 3 (Fig. 3, Table 2). So, we are coming to conclusion that indantrione 2 in FSO3H-SbF5 undergoes only double protonation resulting in dication 4 formation. In Ref. [8] the formation of the isomeric dication 7 (Fig. 3) as intermediate in acid-catalyzed condensations of ninhydrin with aromatic compounds was supposed. However, we believe that in FSO3H-SbF5 this dication is not the preferred isomer. According to quantum chemical calculations, dication 7 is 15.4 kcal/mol less stable than dication 4 in gas phase (CCSD/L1) and 9.9 kcal/mol less stable than dication 4 in CF3SO3H (DFT/PBE0/6-31þG**) [10]. Isomerization barrier of dication 7 into 4 is low: 6.8 kcal/mol (DFT/
Fig. 1. 1H NMR spectrum of dications 6 (¼OþH and C(OH)2 regions are shown) in FSO3H-SbF5/SO2ClF/CD2Cl2 at 110 C. Vertical numbers label integral intensities obtained from deconvolution of the overlapped peaks. Marked by asterisk is the signal of the ]OþH group of dication 4.
PBE/L1). Experimental data also reject the formation of dication 7 in FSO3H-SbF5. The 1H NMR spectrum at 100 C (Fig. 2) contains narrow signals of two pairs of chemically equivalent aromatic protons (H4,7 and H5,6) and exactly two chemically equivalent OHþ groups. This NMR spectrum unambiguously corresponds to the symmetrical structure of dication 4, with the complete signal assignment confirmed by 2D HMBC. On the contrary, the chemical structure of dication 7 is nonsymmetrical, it should give distinct signals of nonequivalent OHþ groups and aromatic protons, while proton exchange, if any, is too slow in the NMR time scale to ensure full signals averaging under these conditions. Furthermore, the calculated 13C NMR chemical shifts of hypothetical dication 7 also do not match the experimental ones (mean square deviation is 22.7 ppm vs. 5.2 ppm for dication 4, Table 2).
2.2. Indan-1,2,3-trione in CF3SO3H The results of quantum chemical calculations [10] claimed that although monoprotonated species can be formed from indan-1,2,3trione in CF3SO3H, the extent of protonation is very low. However, our experimental data do not support the conclusion on a low extent of protonation. On transition from CDCl3 to CF3SO3H-CD2Cl2 significant changes appear in the NMR spectra of indantrione 2: signals of the aromatic protons in 1H NMR spectra are downfielded by 0.5 ppm (SI, p. S7); the signal of C2 in the 13C NMR spectrum is displaced by 7 ppm to a high field, the other 13C NMR signals are downfielded by 7.6÷1 ppm (Table 1, SI, p. S6). Shift of the majority of signals to the low field is typical for protonation of organic compounds. Comparison of the experimental and calculated 13C NMR chemical shifts of the protonated forms (Table 2, SI, p. S8) shows that indan-1,2,3-trione in CF3SO3H must exist mainly in the monoprotonated form 5. Formation of the alternative monoprotonated form 8 (Fig. 3) is hardly probable. According to quantum chemical calculations, it is significantly less stable (by 11.2 kcal/mol
Scheme 3. Protonation of ninhydrin.
G.E. Salnikov et al. / Journal of Molecular Structure 1134 (2017) 1e5
3
Scheme 4. Pathways to dication 4.
Table 2 Mean square deviations (ppm) between the experimental and calculated 13C NMR chemical shifts of indantrione 2 and its protonated forms 5, 8, 4, 7, 3 in specified media. Calculated chemical shift values of C1,3, C4,7, C5,6, C3a,7a are mutually averaged.
Fig. 2. 1H NMR spectrum of dication 4 in FSO3H-SbF5/SO2ClF/CD2Cl2 at 100 C. Vertical numbers label integral intensities. Table 1 13 C NMR chemical shifts of indantrione 2. Media (temperature, C)
CDCl3 (60 ) DMSO-d6 (24 ) CF3SO3H/CD2Cl2 (22 ) FSO3H-SbF5/SO2 (70 ) [7] FSO3H-SbF5 (22 ) FSO3H-SbF5/SO2ClF/CD2Cl2 (100 )
C1,3
C2
C4,7
C5,6
C3a,7a
181.6 183.7 188.1 191.3 192.3 192.5
192.4 186.8 185.4 172.0 171.1 171.3
125.3 124.0 129.9 136.4 137.2 138.8
138.0 136.7 145.5 153.5 154.3 155.5
142.0 140.1 142.9 138.7 139.2 139.2
Scheme 5. Mesomeric structures of trication 3.
Media
2
Z-5
8
ZZ-4
ZE-7
ZZE-3
CDCl3 CF3SO3H FSO3H-SbF5
3.0 8.5 17.1
8.2 6.6 10.4
18.3 21.6 28.1
17.9 12.9 5.2
19.2 19.3 22.7
23.3 20.6 19.3
in gas phase and 9.0 kcal/mol in CF3SO3H [10]). Its calculated chemical shifts fit the experimental ones also much worse (mean square deviation is 21.6 ppm for form 8 vs. 6.6 ppm for form 5). 2.3. Coupling constants 13C-1H and 13C-13C in neutral and protonated forms of ninhydrin and indan-1,2,3-trione Coupling constants are important parameters for studies of chemical structure and stereochemistry in organic compounds. One-bond couplings 1JCH are known to increase on addition of an electronegative substituent or placing a positive charge, presumably due to increase of the s-character of the corresponding CHbond. Indeed, both coupling constants 1J4CH and 1J5CH (Table 3), while showing low sensitivity to solvent change and transition from indantrione to ninhydrin, increase significantly on protonation in CF3SO3H and even more in FSO3H-SbF5. Quantum chemical (SOPPA) calculations reproduce this tendency. It is worth to note that most close to the experimental values of 1JCH measured in the solution of indantrione in CF3SO3H are calculated constants of monocations Z-5 and 8 (accuracy being better than 3 Hz), and to that measured in the solution in FSO3H-SbF5 e calculated constants of dications ZZ-4 and ZE-7 (Fig. 3). The calculated values of 1JCH in hypothetical trication ZZE-3 exceed the experimental ones too
Fig. 3. The results of quantum chemical calculations (CCSD/L1). The most stable conformers of the protonated forms of indantrione 2 are shown. The proton affinity values are shown under the arrows. 13C and 1H (in parentheses) chemical shifts are calculated by the DFT/PBE0/IGLO-II method. NICS(1) values (ppm) calculated by the DFT/PBE/L22 method are shown centered within cycles.
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G.E. Salnikov et al. / Journal of Molecular Structure 1134 (2017) 1e5
Table 3 Experimental and calculated (SOPPA/MP2) coupling constants nJCC and 1JCH (Hz). Calculated coupling constants for monocations Z-5 and 8, dication ZE-7, and trication ZZE-3 are averaged according to the symmetry of their carbon cores. Experimental couplings nJCC of indantrione 2 in CDCl3 are not available because of low solubility. 1
1
J1,2
J1,7a
1
1
2
3
J3a,4
J4,5
J2,3a
J3a,6
1
J4CH
1
J5CH
Experimental (media) Indantrione 2 (CDCl3) Indantrione 2 (DMSO-d6) Ninhydrin 1 (DMSO-d6) Monocation 5 (CF3SO3H) Dication 4 (FSO3H-SbF5) Calculated Indantrione 2 Indantrione 2 þ DMSO Ninhydrin 1 Monocation Z-5 Monocation 8 Dication ZZ-4 Dication ZE-7
56.7 56.4 50.6 56
55.5 50.7 58.7 63
59.3 58.7 58.1 59
55.6 55.5 55.7 53
18.5 16.9 16.6 11
8.9 8.5 7.8
170 168.5 167.3 174.6 182
164 164.7 165.0 169.3 176
52.7 57.5 57.0 51.0 38.1 51.8 43.8
51.8 54.9 51.8 58.9 63.8 64.7 69.1
60.1 61.5 60.7 59.5 60.8 60.5 59.8
58.5 59.0 58.2 56.1 56.8 52.0 53.4
18.5 18.3 16.9 16.1 21.6 9.7 19.1
9.0 9.1 8.5 7.8 8.1 7.1 4.9
167.1 167.2 166.6 177.1 175.1 184.8 188.1
161.6 162.3 161.1 171.9 170.8 183.1 182.9
Trication ZZE-3
55.2
67.1
60.2
49.6
13.0
4.4
193.0
195.0
much, thus rejecting the assumption on the possibility of trication formation. Some 13Ce13C coupling constants are sensitive to protonation of indantrione as well. Most pronounced is increase of the one-bond coupling 1J1,7a and decrease of the long-range coupling 2J2,3a upon transition from indantrione to monocation and dication, adequately reproduced by SOPPA calculations (Table 3). As with 1 JCH, calculated nJCC of hypothetical trication fit the experimental values unsatisfactorily. The values of 1J1,2, 1J1,7a, 2J2,3a, very different for the hypothetical isomers of the monocation (Z-5 or 8) and dication (ZZ-4 or ZE-7), allow to distinguish the primary isomer in the each pair and confirm the formation of monocation Z-5 and dication ZZ-4, correspondingly. Calculated coupling constants in the free indantrione are not sufficiently close to the experimental values measured in the DMSO-d6 solution. To reproduce them better, the geometry optimized model complex of indantrione with one DMSO molecule was used for SOPPA calculation (Table 3, SI, p. S9). 2.4. Indan-1,2,3-trione as acidity indicator Significant dependence of 13C NMR chemical shifts of indantrione 2 on media acidity (SI, p. S6) allows using this compound as a convenient acidity indicator. Most sensitive is the difference between chemical shifts of C2 and C5,6, its dependence on acidity is smooth and monotonic (Fig. 4). Advantages of indan-1,2,3-trione as an acidity indicator: - it covers a wide range of acidity (H0 3 ÷ 25) - it can be easily obtained from ninhydrin by keeping the latter at 120 C or sublimation in vacuum. - it is readily soluble in acids, the concentration of the resulting solutions is quite enough for a fast 13C NMR spectra registration. 3. Conclusions Our data obtained by NMR in combination with the results of quantum chemical calculations shed a bright light on chemical behavior of ninhydrin and indan-1,2,3-trione in acidic media. The conclusions on the matter based solely on experimental or theoretical data available in chemical literature (formation of trication in FSO3H-SbF5 [7] and exclusively low extent of protonation in CF3SO3H [10] respectively) have been disproved. In FSO3H-SbF5 dication is formed; in CF3SO3H the extent of protonation of indan1,2,3-trione is very high, monocation being formed. This demonstrates fruitfulness of such a combined experimental and
Fig. 4. Calibration curve of indan-1,2,3-trione as H0 indicator.
theoretical approach for reliable determination of chemical structures. 4. Experimental 4.1. General methods and materials NMR spectra were obtained at the Chemical Service Center of Siberian Branch of the Russian Academy of Sciences on Bruker AV600 and AV-400. Residual proton and carbon signals of CD2Cl2 (dH 5.33 ppm, dC 53.6 ppm), CDCl3 (dH 7.24 ppm, dC 76.9 ppm) or Me4NþBF 4 (dH 3.19 ppm, dC 56.5 ppm) were used as internal standards. Doubly distilled FSO3H (b.p. 158e161 C), freshly distilled SbF5, CF3SO3H (from ABCR), distilled CF3COOH, H2SO4 d20 1.82 (92%) were used. CD2Cl2 and CDCl3 were drained by 4 Å molecular sieves. SO2ClF was prepared by the method of Woyski [11]. Indan-1,2,3trione was prepared from ninhydrin (“zur Analyse” from VEB LABORCHEMIE APOLDA) by vacuum sublimation (1 mm Hg, 120 C) [12]. 4.2. Protonation of ninhydrin Suspension of ninhydrin 1 (20 mg, 0.112 mmol) in 0.12 mL of
G.E. Salnikov et al. / Journal of Molecular Structure 1134 (2017) 1e5
CD2Cl2 was added to solution of FSO3H-SbF5 (1:1 m/m, 355 mg, 1.1 mmol) in 0.25 mL of SO2ClF placed into NMR tube at 95 C (acetone e liquid N2 bath) and was mixed by glass stick. 4.3. Protonation of indan-1,2,3-trione Indantrione 2 (20e130 mg, 0.12e0.8 mmol) was placed in NMR tube, 0.4 mL of acid was added. In the cases of FSO3H, CF3SO3H and CF3COOH 0.1 mL of CD2Cl2 was added for deuterium lock and as internal standard. In the cases when CD2Cl2 is not soluble (H2SO4) or reacts with acid (FSO3H-SbF5) Me4NþBF 4 was used as internal standard. The content of NMR tube was mixed by shaking at ambient temperature or in warm water bath. According to NMR spectra, the protonation products composition depends on the acidic system only and not on the initial indantrione concentration. 4.4. Quantum chemical calculations The geometry parameters of ninhydrin, indan-1,2,3-trione and their protonated forms were optimized by DFT/PBE [13], riMP2 and CCSD methods (Priroda program [14], L1 basis L01 [15], cc-pVDZ analog). Cluster of the Information Computation Center, Novosibirsk State University (http://www.nusc.ru/) was used. Chemical shifts (DFT/PBE0/IGLO-II) and spin-spin coupling constants (SOPPA [16], locally dense basis: cc-pVDZ-Cs for carbon atoms, aug-ccpVTZ-J without d-functions for protons, cc-pVDZ for oxygen atoms) were calculated by Dalton program [17]. Acknowledgements G.E. Salnikov and A.M. Genaev gratefully acknowledge financial support from the RSF (grant 16-13-10151). Prof. V. G. Shubin is
5
grateful to the Chemistry and Material Science Department of the Russian Academy of Sciences (project no. 5.1.4) for financial support of his work. Appendix A. Supplementary data Supplementary data related to this article can be found at http:// dx.doi.org/10.1016/j.molstruc.2016.12.057. References [1] R.R. Naredla, D.A. Klumpp, Chem. Rev. 113 (2013) 6905e6948. [2] G.A. Olah, D.A. Klumpp, Superelectrophiles and Their Chemistry, J. Wiley & Sons, New York, 2008. [3] D.A. Klumpp, S. Fredrick, S. Lau, K.K. Jin, R. Bau, G.K.S. Prakash, G.A. Olah, J. Org. Chem. 64 (1999), 5152e5155 and references cited therein. [4] H.N. Song, H.J. Lee, M.R. Seong, K.S. Jung, J.N. Kim, Synth. Commun. 30 (2000) 1057e1066. [5] S.K. Kundu, S. Das, A. Pramanik, Ind. J. Chem. 43B (2004) 2212e2216. [6] A. Kundu, A. Pramanik, Mol. Divers. (2016), http://dx.doi.org/10.1007/s11030016-9661-3. [7] D. Bruck, A. Dagan, M. Rabinovitz, Tetrahedron Lett. 20 (1978) 1791e1794. [8] A.M.C. Herath, R.M.G. Rajapakse, V. Karunarathne, A. Wicramasinghe, Electrochim. Acta 51 (2006) 2890e2897. [9] A.L. Lira, M.G. Zolotukhin, L. Fomina, S. Fomine, Macromol. Theory Simul. 16 (2007) 227e239. [10] D.R. Nieto, M.G. Zolotukhin, L. Fomina, S. Fomine, J. Phys. Org. Chem. 23 (2010) 878e884. [11] M.M. Woyski, J. Am. Chem. Soc. 72 (1950) 919e921. [12] T. Itoh, J. Tatsugi, H. Tomioka, Bull. Chem. Soc. Jpn. 82 (2009) 475e481. [13] J.P. Perdew, K. Burke, M. Ernzerhof, Phys. Rev. Lett. 77 (1996) 3865e3868. [14] (a) D.N. Laikov, Chem. Phys. Lett. 281 (1997) 151e156; (b) D.N. Laikov, Y.A. Ustynyuk, Russ. Chem. Bull. 54 (2005) 820e826. [15] D.N. Laikov, Chem. Phys. Lett. 416 (2005) 116e120. [16] H. Kjær, S.P.A. Sauer, J. Kongsted, J. Chem. Phys. 133 (2010), 144106. [17] Release 2.0, DALTON, a Molecular Electronic Structure Program, 2005. see, http://www.kjemi.uio.no/software/dalton/dalton.html.
Contents lists available at ScienceDirect
Journal of Molecular Structure journal homepage: http://www.elsevier.com/locate/molstruc
Protonation of ninhydrin and indan-1,2,3-trione revisited: A combined theoretical and experimental study George E. Salnikov a, b, Alexander M. Genaev a, *, Andrey V. Shernyukov a, Vyacheslav G. Shubin a a b
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Academician Lavrent'ev Ave. 9, Novosibirsk 630090, Russian Federation Novosibirsk State University, Pirogova St. 2, Novosibirsk, 630090, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history: Received 18 July 2016 Received in revised form 21 December 2016 Accepted 22 December 2016 Available online 23 December 2016
The literature data on protonation of indan-1,2,3-trione and ninhydrin (indantrione hydrate) in acidic media are inconsistent, formation of dications at pH 3 and very low extent of protonation in superacid CF3SO3H were claimed. Our combined theoretical (DFT, MP2, CCSD) and experimental (NMR) study has shown that indantrione undergoes single protonation in CF3SO3H resulting in monocation formation. In more strong superacid FSO3H-SbF5 dication is formed, but, contrary to the literary data, trication is not formed even in this superacid. Significant dependence of 13C NMR chemical shifts of indantrione on media acidity allows using this compound as a convenient indicator of acidity in a broad range, from H0 3 to 25. © 2016 Elsevier B.V. All rights reserved.
Keywords: Ninhydrin Superacid NMR Quantum chemistry calculations
1. Introduction Carbocation chemistry has been a hot research area for many years [1]. Among carbocations multiply charged cations as superelectrophilic species are of particular interest [2], they are capable to interact with weak nucleophiles. Acid-catalyzed condensation of ninhydrin with aromatic compounds [3e6] is a typical example. Data on structure of protonated forms of ninhydrin 1 and indan1,2,3-trione 2 (dehydrated ninhydrin, Scheme 1) are necessary for understanding the mechanism of these reactions. However, the available data on the matter are not certain. The authors of paper [7] interpreted data of 1H and 13C NMR spectroscopy obtained for solution of ninhydrin in superacid FSO3H-SbF5 as indicating the formation of trication 3 (Scheme 2), and according to authors' of article [8] assumption dication 4 can be formed even in weakly acidic solutions at pH 3. Recently indantrione 2 protonation was studied theoretically on the basis of approach described earlier [9]. It was found that protonation proceeds mainly on the oxygen atoms of the carbonyl groups 1 and 3 sequentially leading to monocation 5 and dication 4 [10]. On the other hand, the data presented in this work predict that in superacid CF3SO3H indantrione 2 must exist
* Corresponding author. E-mail address: [email protected] (A.M. Genaev). http://dx.doi.org/10.1016/j.molstruc.2016.12.057 0022-2860/© 2016 Elsevier B.V. All rights reserved.
mainly in nonprotonated form. To clarify the situation we have studied protonation of ninhydrin and indantrione in a broad range of acids, from CF3COOH to superacids. 2. Results and discussion 2.1. Ninhydrin and indan-1,2,3-trione in FSO3H-SbF5 The 1H NMR data show that nynhydrin 1 in FSO3H-SbF5/SO2ClF/ CD2Cl2 at low temperatures undergoes protonation resulting in dication 6 formation (Scheme 3, SI, supporting information, p. S2). Indicative are the two signals of the geminal hydroxy groups in the region between 5.5 and 6.0 ppm and the three signals of the protonated carbonyl groups in the region between 15.5 and 16.5 ppm (Fig. 1). According to quantum chemical calculations by DFT и MP2 methods (SI, p. S4) the most stable structures of dication 6 are EZ and ZZ conformers, their interconversion being slowed down. Upon increasing the temperature to 80 C dehydration occurs (Scheme 4), confirmed by increase of H3Oþ signal intensity. In 1H NMR spectrum of the particle formed (Fig. 2, SI, p. S5) at 100 C a signal of the protonated carbonyl groups at d 16.1 ppm is observed. 13 C NMR data (Table 1) show that the same particle is formed from ninhydrin 1 and indantrione 2 in FSO3H-SbF5 at room temperature. This particle was observed by the authors of [7] in FSO3H-SbF5/SO2 at 70 C, but the signal of protonated carbonyl groups in 1H NMR
2
G.E. Salnikov et al. / Journal of Molecular Structure 1134 (2017) 1e5
Scheme 1. Reversible dehydration of ninhydrin.
Scheme 2. Protonation of indan-1,2,3-trione.
spectrum was not detected obviously due to a rapid exchange with acidic medium. Indeed, we have found that upon increasing the temperature this signal broadens, almost merging at 80 C with base line (SI, p. S5). The authors of [7] came to conclusion that indantrione 2 undergoes triple protonation in FSO3H-SbF5/SO2 and the trication formed can be considered either a 5C-2p or a 9C-6p bridged Huckeloid system (Scheme 5). Aromatic stabilization is expected to facilitate triple protonation. Indeed, NICS calculations (Fig. 3) show that trication 3 is aromatic. However, DFT/PBE, MP2 and CCSD calculations (gas phase) indicate very low probability of trication 3 formation from dication 4 due to negative proton affinity of the latter (Fig. 3). PBE0/aug-ccpvtz calculations [10] show that the formation of trication 3 is also unfavorable in solution: the Gibbs free energy of dication 4 protonation in TfOH is 35.5 kcal/mol. It is natural to expect that protonation of indantrione 2 in FSO3H-SbF5 should lead to formation of dication 4, not trication 3. The experimental data we have obtained support this suggestion: only one signal in region of the protonated carbonyl groups in 1H NMR spectra at low temperatures is observed (Fig. 2), the intensity of this signal corresponds to 2H, as the most stable conformer of dication 4 has C2v symmetry (Fig. 3) while in case of trication 3 formation appearance of three low-field signals of equal intensity (1H each) would be expected. 13C NMR chemical shifts of indantrione 2 in FSO3H-SbF5 are in a good accordance with the calculated ones for dication 4 and do not correspond to trication 3 (Fig. 3, Table 2). So, we are coming to conclusion that indantrione 2 in FSO3H-SbF5 undergoes only double protonation resulting in dication 4 formation. In Ref. [8] the formation of the isomeric dication 7 (Fig. 3) as intermediate in acid-catalyzed condensations of ninhydrin with aromatic compounds was supposed. However, we believe that in FSO3H-SbF5 this dication is not the preferred isomer. According to quantum chemical calculations, dication 7 is 15.4 kcal/mol less stable than dication 4 in gas phase (CCSD/L1) and 9.9 kcal/mol less stable than dication 4 in CF3SO3H (DFT/PBE0/6-31þG**) [10]. Isomerization barrier of dication 7 into 4 is low: 6.8 kcal/mol (DFT/
Fig. 1. 1H NMR spectrum of dications 6 (¼OþH and C(OH)2 regions are shown) in FSO3H-SbF5/SO2ClF/CD2Cl2 at 110 C. Vertical numbers label integral intensities obtained from deconvolution of the overlapped peaks. Marked by asterisk is the signal of the ]OþH group of dication 4.
PBE/L1). Experimental data also reject the formation of dication 7 in FSO3H-SbF5. The 1H NMR spectrum at 100 C (Fig. 2) contains narrow signals of two pairs of chemically equivalent aromatic protons (H4,7 and H5,6) and exactly two chemically equivalent OHþ groups. This NMR spectrum unambiguously corresponds to the symmetrical structure of dication 4, with the complete signal assignment confirmed by 2D HMBC. On the contrary, the chemical structure of dication 7 is nonsymmetrical, it should give distinct signals of nonequivalent OHþ groups and aromatic protons, while proton exchange, if any, is too slow in the NMR time scale to ensure full signals averaging under these conditions. Furthermore, the calculated 13C NMR chemical shifts of hypothetical dication 7 also do not match the experimental ones (mean square deviation is 22.7 ppm vs. 5.2 ppm for dication 4, Table 2).
2.2. Indan-1,2,3-trione in CF3SO3H The results of quantum chemical calculations [10] claimed that although monoprotonated species can be formed from indan-1,2,3trione in CF3SO3H, the extent of protonation is very low. However, our experimental data do not support the conclusion on a low extent of protonation. On transition from CDCl3 to CF3SO3H-CD2Cl2 significant changes appear in the NMR spectra of indantrione 2: signals of the aromatic protons in 1H NMR spectra are downfielded by 0.5 ppm (SI, p. S7); the signal of C2 in the 13C NMR spectrum is displaced by 7 ppm to a high field, the other 13C NMR signals are downfielded by 7.6÷1 ppm (Table 1, SI, p. S6). Shift of the majority of signals to the low field is typical for protonation of organic compounds. Comparison of the experimental and calculated 13C NMR chemical shifts of the protonated forms (Table 2, SI, p. S8) shows that indan-1,2,3-trione in CF3SO3H must exist mainly in the monoprotonated form 5. Formation of the alternative monoprotonated form 8 (Fig. 3) is hardly probable. According to quantum chemical calculations, it is significantly less stable (by 11.2 kcal/mol
Scheme 3. Protonation of ninhydrin.
G.E. Salnikov et al. / Journal of Molecular Structure 1134 (2017) 1e5
3
Scheme 4. Pathways to dication 4.
Table 2 Mean square deviations (ppm) between the experimental and calculated 13C NMR chemical shifts of indantrione 2 and its protonated forms 5, 8, 4, 7, 3 in specified media. Calculated chemical shift values of C1,3, C4,7, C5,6, C3a,7a are mutually averaged.
Fig. 2. 1H NMR spectrum of dication 4 in FSO3H-SbF5/SO2ClF/CD2Cl2 at 100 C. Vertical numbers label integral intensities. Table 1 13 C NMR chemical shifts of indantrione 2. Media (temperature, C)
CDCl3 (60 ) DMSO-d6 (24 ) CF3SO3H/CD2Cl2 (22 ) FSO3H-SbF5/SO2 (70 ) [7] FSO3H-SbF5 (22 ) FSO3H-SbF5/SO2ClF/CD2Cl2 (100 )
C1,3
C2
C4,7
C5,6
C3a,7a
181.6 183.7 188.1 191.3 192.3 192.5
192.4 186.8 185.4 172.0 171.1 171.3
125.3 124.0 129.9 136.4 137.2 138.8
138.0 136.7 145.5 153.5 154.3 155.5
142.0 140.1 142.9 138.7 139.2 139.2
Scheme 5. Mesomeric structures of trication 3.
Media
2
Z-5
8
ZZ-4
ZE-7
ZZE-3
CDCl3 CF3SO3H FSO3H-SbF5
3.0 8.5 17.1
8.2 6.6 10.4
18.3 21.6 28.1
17.9 12.9 5.2
19.2 19.3 22.7
23.3 20.6 19.3
in gas phase and 9.0 kcal/mol in CF3SO3H [10]). Its calculated chemical shifts fit the experimental ones also much worse (mean square deviation is 21.6 ppm for form 8 vs. 6.6 ppm for form 5). 2.3. Coupling constants 13C-1H and 13C-13C in neutral and protonated forms of ninhydrin and indan-1,2,3-trione Coupling constants are important parameters for studies of chemical structure and stereochemistry in organic compounds. One-bond couplings 1JCH are known to increase on addition of an electronegative substituent or placing a positive charge, presumably due to increase of the s-character of the corresponding CHbond. Indeed, both coupling constants 1J4CH and 1J5CH (Table 3), while showing low sensitivity to solvent change and transition from indantrione to ninhydrin, increase significantly on protonation in CF3SO3H and even more in FSO3H-SbF5. Quantum chemical (SOPPA) calculations reproduce this tendency. It is worth to note that most close to the experimental values of 1JCH measured in the solution of indantrione in CF3SO3H are calculated constants of monocations Z-5 and 8 (accuracy being better than 3 Hz), and to that measured in the solution in FSO3H-SbF5 e calculated constants of dications ZZ-4 and ZE-7 (Fig. 3). The calculated values of 1JCH in hypothetical trication ZZE-3 exceed the experimental ones too
Fig. 3. The results of quantum chemical calculations (CCSD/L1). The most stable conformers of the protonated forms of indantrione 2 are shown. The proton affinity values are shown under the arrows. 13C and 1H (in parentheses) chemical shifts are calculated by the DFT/PBE0/IGLO-II method. NICS(1) values (ppm) calculated by the DFT/PBE/L22 method are shown centered within cycles.
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G.E. Salnikov et al. / Journal of Molecular Structure 1134 (2017) 1e5
Table 3 Experimental and calculated (SOPPA/MP2) coupling constants nJCC and 1JCH (Hz). Calculated coupling constants for monocations Z-5 and 8, dication ZE-7, and trication ZZE-3 are averaged according to the symmetry of their carbon cores. Experimental couplings nJCC of indantrione 2 in CDCl3 are not available because of low solubility. 1
1
J1,2
J1,7a
1
1
2
3
J3a,4
J4,5
J2,3a
J3a,6
1
J4CH
1
J5CH
Experimental (media) Indantrione 2 (CDCl3) Indantrione 2 (DMSO-d6) Ninhydrin 1 (DMSO-d6) Monocation 5 (CF3SO3H) Dication 4 (FSO3H-SbF5) Calculated Indantrione 2 Indantrione 2 þ DMSO Ninhydrin 1 Monocation Z-5 Monocation 8 Dication ZZ-4 Dication ZE-7
56.7 56.4 50.6 56
55.5 50.7 58.7 63
59.3 58.7 58.1 59
55.6 55.5 55.7 53
18.5 16.9 16.6 11
8.9 8.5 7.8
170 168.5 167.3 174.6 182
164 164.7 165.0 169.3 176
52.7 57.5 57.0 51.0 38.1 51.8 43.8
51.8 54.9 51.8 58.9 63.8 64.7 69.1
60.1 61.5 60.7 59.5 60.8 60.5 59.8
58.5 59.0 58.2 56.1 56.8 52.0 53.4
18.5 18.3 16.9 16.1 21.6 9.7 19.1
9.0 9.1 8.5 7.8 8.1 7.1 4.9
167.1 167.2 166.6 177.1 175.1 184.8 188.1
161.6 162.3 161.1 171.9 170.8 183.1 182.9
Trication ZZE-3
55.2
67.1
60.2
49.6
13.0
4.4
193.0
195.0
much, thus rejecting the assumption on the possibility of trication formation. Some 13Ce13C coupling constants are sensitive to protonation of indantrione as well. Most pronounced is increase of the one-bond coupling 1J1,7a and decrease of the long-range coupling 2J2,3a upon transition from indantrione to monocation and dication, adequately reproduced by SOPPA calculations (Table 3). As with 1 JCH, calculated nJCC of hypothetical trication fit the experimental values unsatisfactorily. The values of 1J1,2, 1J1,7a, 2J2,3a, very different for the hypothetical isomers of the monocation (Z-5 or 8) and dication (ZZ-4 or ZE-7), allow to distinguish the primary isomer in the each pair and confirm the formation of monocation Z-5 and dication ZZ-4, correspondingly. Calculated coupling constants in the free indantrione are not sufficiently close to the experimental values measured in the DMSO-d6 solution. To reproduce them better, the geometry optimized model complex of indantrione with one DMSO molecule was used for SOPPA calculation (Table 3, SI, p. S9). 2.4. Indan-1,2,3-trione as acidity indicator Significant dependence of 13C NMR chemical shifts of indantrione 2 on media acidity (SI, p. S6) allows using this compound as a convenient acidity indicator. Most sensitive is the difference between chemical shifts of C2 and C5,6, its dependence on acidity is smooth and monotonic (Fig. 4). Advantages of indan-1,2,3-trione as an acidity indicator: - it covers a wide range of acidity (H0 3 ÷ 25) - it can be easily obtained from ninhydrin by keeping the latter at 120 C or sublimation in vacuum. - it is readily soluble in acids, the concentration of the resulting solutions is quite enough for a fast 13C NMR spectra registration. 3. Conclusions Our data obtained by NMR in combination with the results of quantum chemical calculations shed a bright light on chemical behavior of ninhydrin and indan-1,2,3-trione in acidic media. The conclusions on the matter based solely on experimental or theoretical data available in chemical literature (formation of trication in FSO3H-SbF5 [7] and exclusively low extent of protonation in CF3SO3H [10] respectively) have been disproved. In FSO3H-SbF5 dication is formed; in CF3SO3H the extent of protonation of indan1,2,3-trione is very high, monocation being formed. This demonstrates fruitfulness of such a combined experimental and
Fig. 4. Calibration curve of indan-1,2,3-trione as H0 indicator.
theoretical approach for reliable determination of chemical structures. 4. Experimental 4.1. General methods and materials NMR spectra were obtained at the Chemical Service Center of Siberian Branch of the Russian Academy of Sciences on Bruker AV600 and AV-400. Residual proton and carbon signals of CD2Cl2 (dH 5.33 ppm, dC 53.6 ppm), CDCl3 (dH 7.24 ppm, dC 76.9 ppm) or Me4NþBF 4 (dH 3.19 ppm, dC 56.5 ppm) were used as internal standards. Doubly distilled FSO3H (b.p. 158e161 C), freshly distilled SbF5, CF3SO3H (from ABCR), distilled CF3COOH, H2SO4 d20 1.82 (92%) were used. CD2Cl2 and CDCl3 were drained by 4 Å molecular sieves. SO2ClF was prepared by the method of Woyski [11]. Indan-1,2,3trione was prepared from ninhydrin (“zur Analyse” from VEB LABORCHEMIE APOLDA) by vacuum sublimation (1 mm Hg, 120 C) [12]. 4.2. Protonation of ninhydrin Suspension of ninhydrin 1 (20 mg, 0.112 mmol) in 0.12 mL of
G.E. Salnikov et al. / Journal of Molecular Structure 1134 (2017) 1e5
CD2Cl2 was added to solution of FSO3H-SbF5 (1:1 m/m, 355 mg, 1.1 mmol) in 0.25 mL of SO2ClF placed into NMR tube at 95 C (acetone e liquid N2 bath) and was mixed by glass stick. 4.3. Protonation of indan-1,2,3-trione Indantrione 2 (20e130 mg, 0.12e0.8 mmol) was placed in NMR tube, 0.4 mL of acid was added. In the cases of FSO3H, CF3SO3H and CF3COOH 0.1 mL of CD2Cl2 was added for deuterium lock and as internal standard. In the cases when CD2Cl2 is not soluble (H2SO4) or reacts with acid (FSO3H-SbF5) Me4NþBF 4 was used as internal standard. The content of NMR tube was mixed by shaking at ambient temperature or in warm water bath. According to NMR spectra, the protonation products composition depends on the acidic system only and not on the initial indantrione concentration. 4.4. Quantum chemical calculations The geometry parameters of ninhydrin, indan-1,2,3-trione and their protonated forms were optimized by DFT/PBE [13], riMP2 and CCSD methods (Priroda program [14], L1 basis L01 [15], cc-pVDZ analog). Cluster of the Information Computation Center, Novosibirsk State University (http://www.nusc.ru/) was used. Chemical shifts (DFT/PBE0/IGLO-II) and spin-spin coupling constants (SOPPA [16], locally dense basis: cc-pVDZ-Cs for carbon atoms, aug-ccpVTZ-J without d-functions for protons, cc-pVDZ for oxygen atoms) were calculated by Dalton program [17]. Acknowledgements G.E. Salnikov and A.M. Genaev gratefully acknowledge financial support from the RSF (grant 16-13-10151). Prof. V. G. Shubin is
5
grateful to the Chemistry and Material Science Department of the Russian Academy of Sciences (project no. 5.1.4) for financial support of his work. Appendix A. Supplementary data Supplementary data related to this article can be found at http:// dx.doi.org/10.1016/j.molstruc.2016.12.057. References [1] R.R. Naredla, D.A. Klumpp, Chem. Rev. 113 (2013) 6905e6948. [2] G.A. Olah, D.A. Klumpp, Superelectrophiles and Their Chemistry, J. Wiley & Sons, New York, 2008. [3] D.A. Klumpp, S. Fredrick, S. Lau, K.K. Jin, R. Bau, G.K.S. Prakash, G.A. Olah, J. Org. Chem. 64 (1999), 5152e5155 and references cited therein. [4] H.N. Song, H.J. Lee, M.R. Seong, K.S. Jung, J.N. Kim, Synth. Commun. 30 (2000) 1057e1066. [5] S.K. Kundu, S. Das, A. Pramanik, Ind. J. Chem. 43B (2004) 2212e2216. [6] A. Kundu, A. Pramanik, Mol. Divers. (2016), http://dx.doi.org/10.1007/s11030016-9661-3. [7] D. Bruck, A. Dagan, M. Rabinovitz, Tetrahedron Lett. 20 (1978) 1791e1794. [8] A.M.C. Herath, R.M.G. Rajapakse, V. Karunarathne, A. Wicramasinghe, Electrochim. Acta 51 (2006) 2890e2897. [9] A.L. Lira, M.G. Zolotukhin, L. Fomina, S. Fomine, Macromol. Theory Simul. 16 (2007) 227e239. [10] D.R. Nieto, M.G. Zolotukhin, L. Fomina, S. Fomine, J. Phys. Org. Chem. 23 (2010) 878e884. [11] M.M. Woyski, J. Am. Chem. Soc. 72 (1950) 919e921. [12] T. Itoh, J. Tatsugi, H. Tomioka, Bull. Chem. Soc. Jpn. 82 (2009) 475e481. [13] J.P. Perdew, K. Burke, M. Ernzerhof, Phys. Rev. Lett. 77 (1996) 3865e3868. [14] (a) D.N. Laikov, Chem. Phys. Lett. 281 (1997) 151e156; (b) D.N. Laikov, Y.A. Ustynyuk, Russ. Chem. Bull. 54 (2005) 820e826. [15] D.N. Laikov, Chem. Phys. Lett. 416 (2005) 116e120. [16] H. Kjær, S.P.A. Sauer, J. Kongsted, J. Chem. Phys. 133 (2010), 144106. [17] Release 2.0, DALTON, a Molecular Electronic Structure Program, 2005. see, http://www.kjemi.uio.no/software/dalton/dalton.html.