Spectroscopic and Computational Study of Hydrate vs. Hemiacetal Equilibria in 6,7-Epoxy-6,7-Dihydroquinoline-5,8-Dione

Abstract

The hydration of carbonyl compounds and the formation of hemiacetals have been a topic of interest in organic chemistry. Hydration plays an important role in biological processes. Quinoline derivatives are also biologically active molecules with many applications. Equilibrium between 6,7-epoxy-6,7-dihydroquinoline-5,8-dione and its hydrate or hemiacetal form was investigated in aqueous and alcoholic solutions by NMR spectroscopy. Interestingly, no equilibrium was detected for the hydrocarbon counterpart. It was presumed that the existence of this equilibrium is highly dependent on the electronic structure of the molecule. To further understand the difference in reactivity to such systems, density functional theory (DFT) calculations were performed.

Keywords

• Quinoline
• Quinone
• Hydration
• Hemiacetal

6,7-Epoksi-6,7-Dihidrokinolin-5,8-Dion'da Hidrat ve Hemiasetal Dengelerinin Spektroskopik ve Hesaplamalı Çalışması

Abstract

Karbonil bileşiklerinin hidratasyonu ve hemiasetallerin oluşumu organik kimyada ilgi çekici bir konu olmuştur. Hidratasyon biyolojik işlemlerde özellikle de ilaç salınımında önemli bir rol oynar. Kinolin türevleri de birçok uygulama alanına sahiptir ve çok geniş spektrumda biyolojik olarak aktif moleküllerdir. Bir kinolin türevi olan 6,7-epoksi-6,7-dihidrokinolin-5,8-dion ile hidrat veya hemiasetal formu arasındaki denge, sulu ve alkollü çözeltilerde NMR spektroskopisi ile incelendi. İlginç bir şekilde, hidrokarbon analoğu için bir denge tespit edilmedi. Bu dengenin varlığının molekülün elektronik yapısına (azot atomu molekülün elektronik yapısını değiştirdiğinden) büyük ölçüde bağlı olduğu varsayıldı. Bu tür sistemlere karşı reaktiflikteki farkı daha iyi anlamak için yoğunluk fonksiyonel teorisi (DFT) hesaplamaları yapıldı.

Keywords

• Kinolin
• Kinon
• Hidratasyon
• Hemiasetal

References

1. [1] Greenziad, P., Luz, Z., Samuel, D. 1967. A Nuclear Magnetic Resonance Study of The Reversible Hydration of Aliphatic Aldehydes and Ketones. I. Oxygen-17 and Proton Spectra and Equilibrium Constants. Journal of the American Chemical Society, 89, 749-756.
2. [2] Hilal, S. H., Bornander, L. L., Carreira, L. A. 2005. Hydration Equilibrium Constants of Aldehydes, Ketones and Quinazolines. QSAR & Combinatorial Science, 24, 631−638 and references therein.
3. [3] Spink, E., Hewage, C., Malthouse, J. P. 2007. Determination of the Structure of Tetrahedral Transition State Analogues Bound at the Active Site of Chymotrypsin using 18O and 2H Isotope Shifts in the 13C NMR Spectra of Glyoxal Inhibitors. Biochemistry, 46, 12868−12874. [4] Huang, S., Miller, A. K., Wu, W. 2009. Substantial Formation of Hydrates and Hemiacetals from Pyridinium Ketones. Tetrahedron Letters, 50, 6584−6585.
4. [5] Drahonovsky, D., Lehn, J-M. 2009. Hemiacetals in Dynamic Covalent Chemistry: Formation, Exchange, Selection, and Modulation Processes. The Journal of Organic Chemistry, 74, 8428−8432.
5. [6] Martinez, J. M. L., Romasanta, P. N., Chattah, A. K., Buldain, G. Y. 2010. NMR Characterization of Hydrate and Aldehyde Forms of Imidazole-2-carboxaldehyde and Derivatives. The Journal of Organic Chemistry, 75, 3208−3213.
6. [7] Wang, B., Cao, Z. Hydration of Carbonyl Groups: The Labile H3O+ Ion as an Intermediate Modulated by the Surrounding Water Molecules. Angewandte Chemie International Edition, 2011, 123, 3266−3270.
7. [8] Schmidt, A-K. C., Stark, C. B. W. 2011. TPAP-Catalyzed Direct Oxidation of Primary Alcohols to Carboxylic Acids Through Stabilized Aldehyde Hydrates. Organic Letters, 13, 4164−4167.
8. [9] Rypkema, H. A., Sinha, A., Francisco, J. S. 2015. Carboxylic acid catalyzed hydration of acetaldehyde. The Journal of Physical Chemistry A, 119 (19), 4581−4588.

9. [10] Crespi, A. F., Vega, D., Chattah, A. N., Monti, G. A., Buldain, G. Y., Lazaro-Martinez, J. M. 2016. gem-Diol and Hemiacetal Forms in Formylpyridine and Vitamin-B6-Related Compounds: Solid-State NMR and Single-Crystal X-ray Diffraction Studies. The Journal of Physical Chemistry A, 120 (39), 7778−7785.
10. [11] Guthrie, J. P. 1975. Carbonyl Addition Reactions: Factors Affecting the Hydrate–Hemiacetal and Hemiacetal–Acetal Equilibrium Constants. Canadian Journal of Chemistry, 53, 898−906.
11. [12] Khankari, R. K., Grant, D. J. W. 1995. Pharmaceutical Hydrates. Thermochimica Acta, 248, 61-79.
12. [13] Guthrie, J. P. 2000. Hydration of Carbonyl Compounds, an Analysis in Terms of Multidimensional Marcus Theory. Journal of the American Chemical Society, 122, 5529−5538.
13. [14] You, L., Anslyn, E. V. 2009. Secondary alcohol Hemiacetal Formation: An in Situ Carbonyl Activation Strategy. Organic Letters, 11, 5126−5129.
14. [15] Poteet, S. A., McDonnell, F. M. 2013. Water Detection by “turn on” Fluorescence of the Quinone-Containing Complexes [Ru(phen)2(1,10-phenanthroline-5,6-dione)2+] and [Ru(phenanthroline-5,6-dione)3]2+.Dalton Transactions, 42, 13305-13307.
15. [16] Thangavel, A., Elder, I. A., Sotiriou-Leventis. C., Daves, R. 2013. Breaking aggregation and Driving the keto-to-gem-Diol Equilibrium of the N,N′-Dimethyl-2,6-diaza-9,10-Anthraquinonediium Dication to the Keto Form by Intercalation in Cucurbit[7]uril. The Journal of Organic Chemistry, 78, 8297-8304.
16. [17] Seradj, H., Cai, W., Erasga, N. O., Chenault, V. D., Knuckles, A. K., Ragains, J. R., Behforouz, M. 2004. Total Synthesis of Novel 6-Substituted Lavendamycin Antitumor Agents. Organic Letters, 6, 473-476.
17. [18] Baba, A., Kawamura, N., Makino, H., Ohta, Y., Taketomi, S., Sohda, T. 1996. Studies on Disease-Modifying Antirheumatic Drugs:  Synthesis of Novel Quinoline and Quinazoline Derivatives and their anti-Inflammatory Effect. Journal of Medicinal Chemistry, 39, 5176-5182.
18. [19] Prajapati, S. M., Patel, K. D., Vekariya, R-H., Panchala, S. N., Patel, H. D. 2014. Recent Advances in the Synthesis of Quinolines: A Review. RSC Advances, 4, 24463-24476.
19. [20] Thivaios, I., Kakogianni, S., Bokias, G. 2016. A Library of Quinoline-Labeled Water Soluble Copolymers with pH-Tunable Fluorescence Response in the Acidic pH Region. Macromolecules, 49, 3526-3534.
20. [21] Mlochowski, J., Kloc, K., Piatkowska, J. 1982. Oxides of Heterocyclic Quinones. N-Oxides and Epoxides of Quinoline- and Isoquinoline-5,8-dione. Heterocycles, 19, 1889-1894.
21. [22] Zhao, Y., Truhlar, D. G. 2008. The M06 Suite of Density Functionals for Main Group Thermochemistry, Thermochemical Kinetics, Noncovalent Interactions, Excited States, and Transition Elements: Two New Functionals and Systematic Testing of Four M06-Class Functionals and 12 Other Functionals. Theoretical Chemistry Accounts, 120, 215-241.
22. [23] Frisch, M. J.; Trucks, G. W., Schlegel, H. B., et al. 2010. Gaussian 09, Revision B.01. Gaussian, Inc., Wallingford CT.
23. [24] Legault, C. Y. 2009. CYLview, 1.0b; Université de Sherbrooke, Sherbrooke, Queb́ec, Canada.
24. [25] Philips, J. J., Hudspeth, M. A., Browne, Jr. P. M., et al. 2010. Basis Set Dependence of Atomic Spin Populations. Chemical Physics Letters, 495, 146−150 and references therein.
25. [26] Becke, A. D. 1993. Density‐Functional Thermochemistry. III. The Role of Exact Exchange. The Journal of Chemical Physics, 98, 5648−5652.
26. [27] Becke, A. D. 1998. A New Mixing of Hartree–Fock and Local Density‐Functional Theories. The Journal of Chemical Physics, 98, 1372−1377.
27. [28] Lee, C., Yang, W., Parr, R. G. 1988. Development of the Colle-Salvetti Correlation-Energy Formula into a Functional of the Electron Density. Physical Review B, 37, 785−789.
28. [29] Perdew, J. P., Wang, Y. 1992. Accurate and Simple Analytic Representation of the Electron-Gas Correlation Energy. Physical Review B. 45, 13244-13249.
29. [30] Chai, J. D., Head-Gordon M. 2008. Long-Range Corrected Hybrid Density Functionals with Damped Atom–Atom Dispersion Corrections. Physical Chemistry Chemical Physics, 10: 6615–6620.