Influence of Bond Fixation in Benzo-Annulated N-Salicylideneanilines

Influence of Bond Fixation in Benzo-Annulated N-Salicylideneanilines and Their ortho-C(dO)X Derivatives (X ) CH3, NH2, OCH3) on Tautomeric Equilibria in Solution Ryszard Gawinecki,*,† Agnieszka Kuczek,† Erkki Kolehmainen,‡ Borys Os´miałowski,† Tadeusz M. Krygowski,§ and Reijo Kauppinen‡ Department of Chemistry, UniVersity of Technology and Life Sciences, Seminaryjna 3, PL-85-326, Bydgoszcz, Poland, Department of Chemistry, P.O. Box 35, FIN-40014, UniVersity of JyVa¨skyla¨, Finland, and Department of Chemistry, UniVersity of Warsaw, Pasteura 1, PL-02-093 Warsaw, Poland [email protected] ReceiVed March 22, 2007

1

H, 13C, and 15N NMR spectra show that an ortho-C(dO)X group present in the molecules of N-salicylideneanthranilamide (X ) NH2), methyl N-salicylideneanthranilate (X ) OCH3), N-salicylideneo-aminoacetophenone (X ) CH3), and their benzo analogues have only a minor effect on the tautomeric OH/NH-equilibrium in solution. Only two of three possible tautomers were detected. Lability of the absent form was proved by theoretical calculations. Calculated energies show that the enolimino form (OH) is less stable than the enaminone (NH) form only for dibenzo-annulated N-salicylideneanilines. The population of each species in the tautomeric mixture was found to be inversely proportional to its energy. Application of the geometry-based aromaticity index HOMA shows that the effectiveness of the π-electron delocalization in different rings in the molecule depends mostly on the position of benzoannulation. Both the NH‚‚‚O and N‚‚‚HO hydrogen bonds present in the NH and OH tautomers, respectively, increase the aromaticity of the quasirings H-O-CdC-CdN and OdC-CdC-N-H and decrease the aromatic character of the fused benzene ring. These results seem to be reliable when N-salicylideneanilines studied are compared with naphthalene and their benzo-annulated derivatives, i.e., phenanthrene, anthracene, and triphenylene. An analysis of the effectiveness of π-electron delocalization confirms that in all cases studied, the OH form is more stable. Although the HOMA values and calculated energies are not a criterion that allows determination of the dominating tautomer, both of these parameters correctly show the effect of changes in the molecular topology on tautomeric preferences.

Introduction Although all C-C bonds in benzene (D6h symmetry group) are equivalent, in naphthalene (D2h symmetry) the C1-C2 and C2-C3 bond lengths are different. The bonds in anthracene, phenanthrene, and in many other polycyclic benzenoid hydro* Author to whom correspondence should be addressed. Tel: +48 52 3749070, fax: +48 52 3749005. † University of Technology and Life Sciences. ‡ University of Jyva ¨ skyla¨. § University of Warsaw.

carbons are also nonequivalent. Since addition to phenanthrene and its oxidation and reduction take place at the 9,10-positions under conditions at which the C1-C2 bonds in naphthalene and anthracene are either inert or much less reactive, the C9C10 bond in the former compound has much more olefinic character than the latter bonds.1 Although there is only one vicinally disubstituted benzene derivative, two adjacent substituents in the naphthalene derivative can occupy the 1/2, 2/1, or 2/3 positions. Further, the aromaticity of a substituted benzene ring is expected to be 10.1021/jo070454f CCC: $37.00 © 2007 American Chemical Society

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Benzo-Annulated N-Salicylideneanilines

dependent on the character of the attached groups.2 The strength of chelation in vicinally disubstituted naphthalene derivatives depends on the multiplicity of the bond joining the ring carbon atoms holding the two substituents.3 Metal chelates derived from 3-hydroxy-2-naphthaldehyde are less stable than those from its 1,2- or 2,1-isomers.4 In naphthalene this behavior was attributed to the greater double bond character of the C1-C2 bond when compared to the C2-C3 bond.4a Analysis of the ultraviolet spectra of hydroxynaphthaldehydes supports this conclusion.5 IR spectra show that intramolecular hydrogen bonds in 1,2- and 2,1-hydroxyformyl-, hydroxyacetyl-, and hydroxy(methoxycarbonyl)naphthalenes are almost identical by strength6 and are stronger than those in 2,3-substituted isomers.6 Corresponding hydrogen bonds in 9,10-hydroxyformyl-, hydroxyacetyl-, and hydroxy(methoxycarbonyl)phenanthrenes were shown to be the strongest interactions of this type yet encountered in simple aromatic compounds.7 Although aromaticity of the substituted benzene ring in salicyl- and 3-hydroxynaphthalene-2-carbaldehydes is relatively high,8 the intramolecular hydrogen bond in these compounds is weaker than that in the monoenol of malonaldehyde.8,9 On the other hand, the hydrogen bonds in 2-hydroxynaphthalene1-carbaldehyde, 1-hydroxynaphthalene-2-carbaldehyde, and 10hydroxyphenanthrene-9-carbaldehyde are much stronger than that in the monoenol of malonaldehyde.8,9 It is noteworthy that the HO-C-C-CdO fragment in these compounds is considerably more aromatic than those in salicyl- and 3-hydroxynaphthalene-2-carbaldehydes.8,9 On the other hand, the substituted benzene ring in 2-hydroxynaphthalene-1-carbaldehyde, 1-hydroxynaphthalene-2-carbaldehyde, and 10-hydroxyphenanthrene9-carbaldehyde is less aromatic than those in salicyl- and 3-hydroxynaphthalene-2-carbaldehydes.8,9 Chelation in the respective ortho-disubstituted benzenes has an intermediate strength between 1,2- (or 2,1-) and 2,3disubstituted naphthalenes.6 On the basis of evidence derived both from chemical reactions and IR spectra, the highly olefinic nature of the C9-C10 bond in phenanthrene was confirmed.7 Wave numbers of the CdO stretching band,6,7 NMR chemical shifts of the hydroxy H-atoms,10a and vicinal coupling constants for the hydrogens on two carbons of the bond (3JH,H)10b,c for o-hydroxy derivatives of formyl-, acetyl-, and methoxycarbonylbenzenes, naphthalenes, and phenanthrenes depend on multiplicity of the bond joining the ring carbon atoms holding the substituents. On the other hand, not entirely concordant conclusions on the bond fixation in naphthalene can be drawn from a (1) (a) Efros, L. S.; Usp. Khim. 1960, 29, 162-186. (b) Dias, J. R. J. Chem. Inf. Model. 2005, 45, 562-571. (c) Dias, J. R. J. Chem. Inf. Model. 2006, 46, 788-800. (2) Krygowski, T. M.; Ste¸ pien´, B. T.; Cyranski, M. K.; Ejsmont, K. J. Phys. Org. Chem. 2005, 18, 886-891. (3) Krygowski, T. M.; Ste¸ pien´, B. T. Chem. ReV. 2005, 105, 34823512. (4) (a) Calvin, M.; Melchior, N. C. J. Am. Chem. Soc. 1948, 70, 32733275. (b) Baker, W.; Carruthers, G. N. J. Chem. Soc. 1937, 479-483. (5) Hodnett, E. M.; Tai, J. J. Med. Chem. 1971, 14, 1115-1116. (6) Hunsberger, I. M. J. Am. Chem. Soc. 1950, 72, 5626-5635. (7) Hunsberger, I. M.; Ketcham, R.; Gutowsky, H. S. J. Am. Chem. Soc. 1952, 74, 4839-4845. (8) Palusiak, M.; Simon, S.; Sola`, M. J. Org. Chem., 2006, 71, 52415248. (9) Krygowski, T. M.; Zachara, J. E.; Os´miałowski, B.; Gawinecki, R. J. Org. Chem. 2006, 71, 7678-7682. (10) (a) Porte, A. L.; Gutowsky, H. S.; Hunsberger, I. M. J. Am. Chem. Soc., 1960, 82, 5057-5063. (b) Jonathan, N.; Gordon, S.; Dailey, B. P. J. Chem. Phys. 1962, 36, 2443-2448. (c) Cooper, M. A.; Manatt, S. L. J. Am. Chem. Soc. 1969, 91, 6325-6333.

SCHEME 1

comparison of melting points and critical solution temperatures of the 1,2-, 2,1-, and 2,3-hydroxyacetylnaphthalenes,4b the acidities of o-hydroxynaphthaldehydes11 and o-chloronaphthoic acids,12 and the measured bond lengths for the naphthalene derivatives.13 Since proton transfer in numerous aromatic systems involves a migration of the double bond,14 one should observe great changes in the bond lengths for different tautomers. As a consequence, some tautomers of certain aromatic compounds may lose their aromaticity. That is why studies on tautomerism may tell much about bond fixation in aromatic compounds. Several studies15 show that proton transfer in β-amino-R,βunsaturated carbonyl systems, shortly called enaminones, enables these compounds to equilibriate with enolimines and, sometimes, with ketiminones (Scheme 1).16 Both enaminone and enolimine forms can be stabilized by an intramolecular hydrogen bond not only in the solid state but also in nonpolar solvents.15e Although a N‚‚‚H-O intramolecular hydrogen bond is stronger than a N-H‚‚‚O hydrogen bond, tautomeric species stabilized by the latter interaction are usually of lower energy.17 (11) Vargas, V.; Amigo, L. J. Chem. Soc., Perkin Trans. 2 2001, 11241129. (12) Dziembowska, T.; Jagodzin´ska, E.; Rozwadowski, Z.; Kotfica, M. J. Mol. Struct. 2001, 598, 229-234. (13) Robertson, J. M. Proc. R. Soc. London 1933, A142, 674-688. (14) Raczyn´ska, E. D.; Kosin´ska, W.; Os´miałowski, B.; Gawinecki, R. Chem. ReV. 2005, 105, 3561-3612. (15) (a) Kolehmainen, E.; Os´miałowski, B.; Nissinen, M.; Kauppinen, R.; Gawinecki, R. J. Chem. Soc., Perkin Trans. 2 2000, 2185-2191. (b) Kolehmainen, E.; Os´miałowski, B.; Krygowski, T. M.; Kauppinen, R.; Nissinen, M.; Gawinecki, R. J. Chem. Soc., Perkin Trans. 2 2000, 12591266. (c) Gawinecki, R.; Kolehmainen, E.; Loghmani-Khouzani, H.; Os´miałowski, B.; Lova´sz, T.; Rosa, P. Eur. J. Org. Chem. 2006, 28172824. (d) Go´mez-Sa´nchez, A.; Paredes-Leo´n, R.; Ca´mpora, J. Magn. Reson. Chem. 1998, 36, 154-162. (e) Weinstein, J.; Wyman, M. J. Org. Chem. 1958, 23, 1618-1622. (f) Dudek, G. O.; Volpp, G. P. J. Am. Chem. Soc. 1963, 85, 2697-2702. (g) Da¸ browski, J.; Kamien´ska-Trela, K. Spectrochim. Acta 1966, 22, 211-220. (h) Da¸ browski, J.; Da¸ browska, U. Chem. Ber. 1968, 101, 2365-2374. (i) Kania, L.; Kamien´ska-Trela, K.; Witanowski, M. J. Mol. Struct. 1983, 102, 1-17. (j) Brown, N. M. D.; Nonhebel, D. C. Tetrahedron 1968, 24, 5655-5664. (k) Da¸ browski, J.; Kamien´ska-Trela, K. J. Am. Chem. Soc. 1976, 98, 2826-2834. (l) Czerwiska, E.; Kozerski, L.; Boksa, J. Org. Magn. Reson. 1976, 8, 345-349. (m) Kozerski, L.; Von Philipsborn, W. Org. Magn. Reson. 1981, 17, 306-310. (n) Kashima, Ch.; Yamamoto, M.; Sugiyama, N. J. Chem. Soc., C 1970, 111-114. (o) Kashima, Ch.; Aoyama, H.; Yamamoto, Y.; Nishio, T. J. Chem. Soc., Perkin Trans. 2 1975, 665-670. (p) Zhuo, J.-C. Magn. Reson. Chem. 1998, 36, 565-572. (q) Fustero, S.; De la Torre, M. G.; Jofre´, V.; Carlo´n, R. P.; Navarro, A.; Fuentes, A. S. J. Org. Chem. 1998, 63, 8825-8836. (16) Edwards, W. G. H.; Petrov, V. J. Chem. Soc. 1954, 2853-2860.

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β-Amino-R,β-unsaturated carbonyl compounds are capable of undergoing spontaneously conformational and configurational isomerizations in solution.15f-q,18 Enaminone tautomers of 3-aminoacroleins, which are stabilized by intramolecular hydrogen bonds, and their open forms are favored in nonpolar and polar solvents, respectively.15d Benzo-annulation is known to affect the stability of enaminones and their tautomers. The relative energy of the tautomers was found to be governed mainly by a change in the degree of heterocycle aromaticity upon hydrogen transfer, but the strength of the intramolecular hydrogen bond provides also some contribution.19 Thus, only enolimine and ketiminone forms were detected when R1,R2 ) benzo (Scheme 1).15a Further, benzo-annulation of the pyridine ring in molecules of these compounds at 3,4- and/or 5,6positions stabilizes the enaminone tautomer (NH form).14,15b,c In solution, numerous 3,4-benzo-annulated enaminones, i.e., 2-[(phenylamino)methylene]-cyclohexa-3,5-dien-1-ones, were found to be in equilibrium with the usually less stable20 enolimine derivatives, i.e., N-salicylideneamines.11,12,21 Polar solvents, low temperatures, and benzo-annulation both in positions 2,3 and 4,5 favor the NH form.21c,22 The NH tautomer is the only form present in the crystalline state of N-(2-hydroxy1-naphthylmethylidene)aniline21c and the major form detected in solutions of N-(10-hydroxy-9-phenanthrylmethylidene)aniline.20b The proton transfer between N-salicylideneanilines and their enaminone tautomeric forms can take place not only in solution but also in the condensed phase.23 Since the compound under such conditions represents a superposition of the OH and NH tautomers,24 each bond length measured is a weighted average of the corresponding bond lengths in these species according to their molar ratios. It is therefore concluded that the population of the NH tautomer increases with lowering the temperature. Analysis of the molecular geometry shows that the enaminone has a zwitterionic character (it is predominantly quinoid in the gas phase).17a,24b Stabilization of the NH form in (17) (a) Ogawa, K.; Harada, J. J. Mol. Struct. 2003, 647, 211-216. (b) Buemi, G.; Zuccarello, F.; Venuvanalingam, P.; Ramalingam, M. Theor. Chem. Acc. 2000, 104, 226-234. (c) Rybarczyk-Pirek, A.; Grabowski, S. J.; Małecka, M.; Nawrot-Modranka, J. J. Phys. Chem. A 2002, 106, 1195611962. (18) Da¸ browski, J. Spectrochim. Acta 1963, 19, 475-496. (19) Zubatyuk, R. I.; Volovenko, Y. M.; Shishkin, O. V.; Gorb, L.; Leszczyn´ski, J. J. Org. Chem. 2007, 72, 725-735. (20) (a) Cohen, M. D.; Schmidt, G. M. J. J. Phys. Chem. 1962, 66, 24422446. (b) Alarco´n, S. H.; Olivieri, A. C.; Labadie, G. R.; Cravero, R. M.; Gonza´les-Sierra, M. Tert. 1995, 51, 4619-4626. (21) (a) Ferna´ndez-G., J. M.; del Rio-Portilla, F.; Quiroz-Garcı´a, B.; Toscano, R. A.; Salcedo, R. J. Mol. Struct. 2001, 561, 197-207. (b) Sitkowski, J.; Stefaniak, L.; Dziembowska, T.; Grech, E.; Jagodzin´ska, E.; Webb, G. A. J. Mol. Struct. 1996, 381, 177-180. (c) Salman, S. R.; Lindon, J. C.; Farrant, R. D.; Carpenter, T. A. Magn. Reson. Chem. 1993, 31, 991994. (d) Galic´, N.; Cimerman, Z.; Tomis´ic´, V. Anal. Chim. Acta 1997, 343, 135-143. (e) Nazir, H.; Yildiz, M.; Yilmaz, H.; Tahir, M. N.; U ¨ lku¨, D. J. Mol. Struct. 2000, 524, 241-250. (f) Becker, R. S.; Richey, W. F. J. Am. Chem. Soc. 1967, 89, 1298-1302. (g) Hansen, P. E.; Sitkowski, J.; Stefaniak, L.; Rozwadowski, Z.; Dziembowska, T. Ber. Bunsen-Ges. Phys. Chem. 1998, 102, 410-413. (h) Dziembowska, T. Pol. J. Chem. 1998, 72, 193-203. (i) Kro´l-Starzomska, I.; Rospenk, M.; Rozwadowski, Z.; Dziembowska, T. Pol. J. Chem. 2000, 74, 1441-1446. (22) (a) Zhuo, J.-C. Magn. Reson. Chem. 1999, 37, 259-268. (b) Antonov, L.; Fabian, W. M. F.; Nedeltcheva, D.; Kamounah, F. S. J. Chem. Soc., Perkin Trans. 2 2000, 1173-1179. (c) Dudek, G. O.; Dudek, E. P. J. Am. Chem. Soc. 1966, 88, 2407-2412. (d) Joshi, H.; Kamounah, F. S.; van der Zwan, G.; Gooijer, C.; Antonov, L. J. Chem. Soc., Perkin Trans. 2 2001, 2303-2308. (23) Elmali, A.; Kabak, M.; Kavlakoglu, E.; Elerman, Y.; Durlu, T. N. J. Mol. Struct. 1999, 510, 207-214. (24) (a) Sobczyk, L.; Grabowski, S. J.; Krygowski, T. M. Chem. ReV. 2005, 105, 3513-3560. (b) Ogawa, K.; Kasahara, Y.; Ohtani, Y.; Harada, J. J. Am. Chem. Soc. 1998, 120, 7107-2412.

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the crystalline state results primarily from intermolecular hydrogen bonding.24b Changes in the population of the NH and OH tautomers in the crystalline state and in solution with variation of temperature are responsible for the thermochromic properties of numerous salicylideneanilines.17a,20a,24b As suggested by Gilli et al.,25 Schiff bases derived from aromatic o-hydroxyaldehydes show synergism between strength of the hydrogen bond and degree of delocalization of π electrons (however, no dependence between delocalization of the π electrons and the H-bond strength was observed in the crystalline state26). The composition of a tautomeric mixture depends on the stability of the respective tautomers which, in turn, is related to the π-electron delocalization in the molecule and to the strength of the intramolecular hydrogen bond15a,22a,25 (N‚‚‚H-O hydrogen bonds are stronger than N-H‚‚‚O bonds17b,c,24a). Imines of salicylaldehyde are simple models of the respective pyridoxal derivatives which play an important role in enzymatic transformations of R-amino acids27 (all these compounds contain the hydroxy group in the ortho position with respect to the methylideneamine function). The presence of an intramolecular hydrogen bond is essential for the enzymatic properties of Schiff bases of pyridoxal phosphate and R-amino acids. The protontransfer process from oxygen to nitrogen atom in these molecules is the first step of the catalytic cycle.28 Sirtinol, 2-[(2hydroxynaphthalen-1-ylmethylene)amino]-N-(1-phenylethyl)benzamide, the best known inhibitor of the SIRT2 (silent information regulator) which deacetylates R-tubulin and participates in controlling the mitotic exit in the cell cycle,29 is another Schiff base of the same type, which additionally contains the CONHCH(CH3)Ph group. Benzo-annulation is expected to have a stabilizing effect on selected tautomers of N-salicylideneaniline. On the other hand, ortho-C(dO)X substituents in such compounds should enable the formation of additional tautomeric species. Thus, it would be interesting to clarify how these two effects influence the tautomeric equilibria in solutions of N-salicylideneanilines. Aims of the present paper are (i) to show how the position of benzo-annulation in N-salicylideneaniline affects the tautomeric equilibria in solution (one would ask which tautomer, i.e., more or less aromatic, is more stable), and (ii) to clarify the capability of the o-carbonyl group in the “anilinic” benzene ring of these compounds to attract the acidic H-atom. Results and Discussion The N-salicylideneanilines 1-20 presented in Scheme 2 were obtained by simple condensation of the respective aldehyde with substituted anilines (see Experimental Section). Because of the high tendency of some compounds to hydrolyze, we were not able to prepare methyl N-salicylideneanthranilate (11), Nsalicylidene-o-aminoacetophenone (16, known compound30), and (25) Gilli, P.; Bertolasi, V.; Ferretti, V.; Gilli, G. J. Am. Chem. Soc. 2000, 122, 10405-10417. (26) Krygowski, T. M.; Ste¸ pien´, B.; Anulewicz-Ostrowska, R.; Dziembowska, T. Tetrahedron 1999, 55, 5457-5464. (27) (a) Sharif, Sh.; Denisov, G. S.; Toney, M. D.; Limbach, H.-H. J. Am. Chem. Soc. 2006, 128, 3375-3387. (b) Sanz, D.; Perona, A.; Claramunt, R. M.; Elguero, J. Tetrahedron 2005, 61, 145-154. (c) Spies, M. A.; Toney, M. D. Biochemistry 2003, 42, 5099-5107. (d) Malashkevitch, V. N.; Toney, M. D.; Jansonius, J. N. Biochemistry 1993, 32, 13451-13462. (e) Zhou, X.; Toney, M. D. Biochemistry 1999, 38, 311-320. (28) Christen, P., Metzler, P. E., Eds, Transaminases; Wiley: New York, 2005. (29) North, B. J.; Marshall, B. L.; Borra, M. T.; Denu, J. M.; Verdin, E. Mol. Cell 2003, 11, 437-444.

Benzo-Annulated N-Salicylideneanilines SCHEME 2

SCHEME 3

SCHEME 4

N-(3-hydroxy-2-naphthylmethylidene)-o-aminoacetophenone (18), even by modifying the preparative methods described in the Experimental Section as well as that described in the literature30 (the tendency of other compounds, e.g., 8, to react with traces of water present in the NMR solvents is also noteworthy). Unfortunately, literature melting points of some methyl Nsalicylideneanthranilates, which were previously obtained from the respective aldehyde and methyl anthranilate,31 are not disclosed. The formation of different polymorphic crystalline forms and liquid crystal properties of some compounds obtained are probably responsible for the wide melting point ranges and their divergence with literature data (Experimental Section). The NMR spectra, however, confirm that the compounds obtained by us are those expected to be formed in reactions of aldehydes with anilines. In DMSO solution, N-salicylideneanthranilamide (OH form) is in equilibrium with the respective NH tautomer (Scheme 3, X ) NH2).32 One should realize, however, that another (30) Melhior, N. C. J. Am. Chem. Soc. 1949, 71, 3647-3651. (31) Kulkarni, V. H.; Prabhakar, B. K.; Patil, B. R. Monatsh. Chem. 1977, 108, 1305-1312.

enolimine form, i.e., the OH′ tautomer (Scheme 3), can also contribute to the tautomeric equilibrium. The tautomerism of benzo-annulated N-salicylideneanthranilamides has not been studied earlier. Tautomeric equilibria have not been studied either for alkyl N-salicylideneanthranilates,21f N-salicylidene-o-aminoacetophenones,30 or their benzo analogues. These compounds and their tautomers are in fact dibenzo derivatives of cis,cis-bis(βformylvinyl)amine {(2Z,6Z,4E-4-aza-7-hydroxyhepta-2,4,6trienal} (A in Scheme 4), being found to be stabilized by bifurcated hydrogen bonds (no respective (2Z)-3-[((1Z)-3oxoprop-1-enyl)-amino]prop-2-enal tautomeric form, denoted as B in Scheme 4, was detected in solution).33 On the other hand, bis(o-formylphenyl)amine, which is also stabilized by a bifurcated hydrogen bond,34 and N-salicylidene-o-aminoacetophenone are isomeric derivatives of bis(β-formylvinyl)amine that differ from each other only by position of annulation. The presence of additional functions in the molecule may play a crucial role in stabilization of the tautomers. X-ray studies show that N-salicylideneanthranilic acid in the crystalline state is an intermediate between the enolimine and enaminone form.35 The dimer formed is stabilized both by intra- and intermolecular hydrogen bonds. Only the OH form is present in solution (no dimerization takes place there).35 Although all three different tautomers presented in Scheme 3 are stabilized by a bifurcated intramolecular hydrogen bond of RAHB type,36 their relative stability is not known. Because of bifurcation, both the NH and OH forms should be more stable than those tautomers of N-salicylideneaniline which are stabilized only by a single intramolecular hydrogen bond. Multinuclear magnetic resonance spectroscopic techniques have provided an excellent tool to investigate tautomeric equilibria quantitatively.15a,b,37 It has been reported that protonation-caused chemical shift changes of the ring nitrogen atom in aza aromatic compounds are very large.38 Consequently, 15N NMR spectroscopy provides valuable information on their tautomerism.39 One should keep in mind that only one average signal for each nucleus appears in the NMR spectrum of (32) Christie, R. M.; Moss, S. J. Chem. Soc., Perkin Trans. 1 1985, 2779-2783. (33) (a) Da¸ browski, J.; Sˆ wistun, Z. J. Chem. Soc., B 1971, 818-821. (b) Da¸ browski, J.; Sˆ wistun, Z. Tetrahedron 1973, 29, 2261-2267. (34) Da¸ browski, J.; Sˆ wistun, Z.; Da¸ browska, U.; Sˆ wistun, Z. Tetrahedron 1973, 29, 2257-2260. (35) Ligtenbarg, A. G. J.; Hage, R.; Meetsma, A.; Feringa, B. L. J. Chem. Soc., Perkin Trans. 2 1999, 807-812. (36) (a) Gilli, G.; Bellucci, F.; Ferretti, V.; Bertolasi, V. J. Am. Chem. Soc. 1989, 111, 1023-1028. (b) Bertolasi, V.; Gilli, P.; Ferretti, V.; Gilli, G. J. Am. Chem. Soc. 1991, 113, 4917-4925. (c) Gilli, P.; Bertolasi, V.; Ferretti, V.; Gilli, G. J. Am. Chem. Soc. 1994, 116, 909-915. (d) Bertolasi, V.; Gilli, P.; Ferretti, V.; Gilli, G. Chem.-Eur. J. 1996, 2, 925-934.

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Gawinecki et al. TABLE 1. Selected 1H, 13C, and 15N NMR Chemical Shifts (δ) and Coupling Constants (Hz) (in parentheses) of N-Salicylideneanilines 1-20 and Their Tautomers for 0.1-0.2 M Solutions in DMSO-d6 and CDCl3 (italic) at 303 K no.

H7a

H8/H15a

C1

C6

C7

C16

N8b

1

8.95 8.63 9.64 (5.2) 9.31 9.13 8.80 8.95 (6.6) 8.48 (8.2) 9.31 (11.5) 8.84 (11.3) 8.86 (8.7) 8.60 9.42 9.02 8.72 (10.0) 9.03 (12.0) 9.42 (7.1) 9.06 (7.5) 9.03 8.70 8.79 (10.5) 8.13 (9.9) 9.10 (11.8) 8.72 (11.9) 9.35 (7.7) 9.07 (6.5) 8.72 (10.6) 8.59 (8.0) 9.06 (12.1) 8.72 (11.9)

13.08 13.27 15.76 (5.2) 15.48 12.58 12.74 14.86 (6.4) 14.88 (8.2) 15.06 (11.5) 14.84 (11.0) 12.49 (8.7) 12.19 14.32 12.13 14.49 (10.1) 14.72 (12.1) 15.18 (7.1) 15.22 (7.1) 12.40 12.53 14.63 (10.5) 14.75 (9.5) 14.86 (11.8) 14.87 (12.0) 15.00 (7.7) 15.05 (6.5) 14.59 (10.9) 14.77 (8.0) 14.86 (12.0) 15.02 (11.4)

159.22 161.14 170.95

118.04 117.23 108.37

162.42 162.63 155.24

-

-85.3 -85.0 -158.3

170.81 156.03 156.73 173.50

108.75 121.39 121.22 110.30

154.40 163.18 162.51 156.56

-

-150.0 -78.4 -78.5 -189.7

172.34

110.92

156.09

-

-173.7

179.91

104.77

148.08

-

181.23

105.63

146.36

-

159.95

119.66

162.96

168.85

-234.2 (-83.5) -235.4 (-85.1) -85.3

160.75 171.98 155.86 176.31

119.04 108.78 122.01 110.79

165.28 153.96 162.92 153.43

168.29 169.01 168.88 168.93

180.30

105.94

145.65

169.04

-85.4 c -79.0 -214.5 (-74.0) -245.1

174.33

108.86

152.48

166.08

-184.9

176.40

109.27

149.63

166.43

152.41 156.67 178.02

118.77 119.23 111.01

165.89 162.81 152.41

165.89 166.49 165.89

179.08

111.69

150.12

166.49

181.07

106.58

144.95

165.94

182.80

107.87

141.97

166.63

175.00

108.86

151.81

200.02

-192.3 (-71.0) d -78.0 -233.3 (-78.0) -221.3 (-78.0) -250.5 (-92.0) -250.5 (-93.0) -191.5

175.03

109.38

150.85

199.64

-182.6

178.54

111.05

151.82

200.14

-229.7

178.70

111.85

150.12

199.66

-219.9

180.86

106.71

144.73

200.13

182.59

108.11

141.79

199.62

-248.8 (-91.0) -251.7 (-92.3)

2 3 4

5

6 7 8 9 10 12

13 14

15

17

19

20

a

Doublet or broadened singlet; 3J(1H,1H) values are given in parentheses. values are given in parentheses. c Not observed. d Insufficient solubility.

b 1J(1H,15N)

tautomeric mixtures when the proton exchange between individual forms is fast on the NMR time-scale.37e Thus, in the case when basic centers in the tautomers are the strongly electronegative oxygen and nitrogen atoms, integration of the 1H NMR signals is useless for calculation of the contribution of the species present in solution. Since there is almost no influence of benzo-annulation on the 13C chemical shift of carbonyl carbon atom C16 in the 13C NMR spectra of amide (6-10), ester (12-15), and ketone (17, 19, and 20) derivatives of N-salicylideneanilines (Table 1), the OH′ tautomeric form (Scheme 3) seems to be absent in solution (the carbonyl 13C chemical shifts for the compounds studied, shown in Table 1, are typical for the primary amides, esters, 5602 J. Org. Chem., Vol. 72, No. 15, 2007

and ketones40). This conclusion is also verified by the narrow range of the 15N chemical shift (from -270.9 to -262.1 ppm) of the amide nitrogen atom for compounds 6-10. Both 15N chemical shifts and 1JNH (from -89.5 to -88.0 Hz) for these compounds are typical for primary amides.40b The 1H NMR signal of H7 of N-salicylideneanilines 1-20 can be seen at δ ) 8.72-9.64 and 8.13-9.31 ppm in DMSOd6 and CDCl3, respectively (Table 1). It is a singlet for compounds 1, 3, 6, 8, and 13. Splitting due to considerable contribution of the NH tautomer transforms this signal to a doublet (sometimes to a broadened singlet). The 3J(H7,H8) coupling constants, equal to 5.2-12.1 Hz, are typical for enaminones22a). The 1H NMR signals of the acidic H-atom H8/ H15 of N-salicylideneanilines 1-20, seen at δ ) 12.13-15.76 and 12.19-15.48 ppm in DMSO-d6 and CDCl3, respectively (Table 1), is upfield shifted as compared with that of the respective H-atom in the 1H NMR spectra of cis,cis-bis(βacylvinyl)amines.33a Its multiplicity is of the same type as that of H7 (coupling constants J is equal to 5.2-12.0 and 6.5-12.0 Hz in DMSO-d6 and CDCl3, respectively). Significant upfield shift of this signal in the spectra of compounds 1, 3, 6, 8, and 13, as compared to other compounds studied, suggests an increasing amount of the OH form15j,22a (the broadened singlet of the hydroxy H-atom of N-(3-hydroxy-4-pyridinemethylidene)aniline in CDCl3, which contains exclusively the OH form, appears at δ ) 12.76 ppm27b). Splitting of the H8 signal proves that the NH form is present in solution. If one assumes that for the pure NH form 1JNH ) 89 Hz, the tautomeric equilibrium constant in solution of 9 (1JNH ) 74 Hz) can be calculated from equation KT ) [89 - 1J(H,N)]/1J(H,N).22c KT is equal to 0.20 which shows that there exists 83% of the NH form in DMSO solution of 9. The signal of N8 in the 15N NMR spectra of N-salicylideneanilines 1, 3, 6, 8, and 13 can be seen between δ ) -78.0 and -85.3 ppm, both in DMSO-d6 and CDCl3 (Table 1). These values are typical for the OH form41 (the chemical shift of N8 in the NMR spectrum of N-(3-hydroxy-4-pyridinemethylidene)aniline is -67.5 ppm27b). The multiplicity of this signal (singlet) confirms that the OH form is the major contributor in solutions of these compounds.41,42 On the other hand, in the 15N NMR spectra of N-salicylideneanilines 2, 4, 5, 7, 9, 10, 12, 14, 15, (37) (a) Witanowski, M.; Stefaniak, L.; Webb, G. A. Ann. Rep. NMR Spectrosc. 1977, 7, 117-244. (b) 1981, 11B, 1- 493. (c) 1986, 18, 1-761. (d) Dobrowolski, P.; Kamieski, B.; Sitkowski, J.; Stefaniak L.; Chun, Y. Bull. Acad. Polon. Sci., Ser. Sci. Chim. 1988, 36, 203-207. (e) Gawinecki, R.; Kolehmainen, E.; Rasaa, D. J. Phys. Org. Chem. 1995, 8, 689-695. (f) Gawinecki, R.; Os´miałowski, B.; Kolehmainen, E.; Kauppinen, R. J. Phys. Org. Chem. 2001, 14, 201-204. (g) Os´miałowski, B.; Kolehmainen, E.; Nissinen, M.; Krygowski, T. M.; Gawinecki, R. J. Org. Chem. 2002, 67, 3339-3345. (h) Os´miałowski, B.; Laihia, K.; Virtanen, E.; Nissinen, M.; Kolehmainen, E.; Gawinecki, R. J. Mol. Struct. 2003, 654, 61-69. (i) Os´miałowski, B.; Kolehmainen, E.; Gawinecki, R. Chem.-Eur. J. 2003, 9, 2710-2716. (j) Gawinecki, R.; Kolehmainen, E.; Kuczek, A.; Pihlaja, K.; Os´miałowski, B. J. Phys. Org. Chem. 2005, 18, 737-742. (38) Levy, G. C.; Lichter R. L. Nitrogen-15 Nuclear Magnetic Resonance Spectroscopy; Wiley: New York, 1979; p 80. (39) (a) Stefaniak, L. Org. Magn. Reson. 1979, 12, 379-382. (b) Stefaniak, L.; Witanowski M.; Webb, G. A. Polish J. Chem. 1981, 55, 1441-1444. (c) Llor, J.; Lopez-Mayorga; Munoz, L. Magn. Reson. Chem. 1993, 31, 552-556. (40) (a) Silverstein, R. M.; Bassler, G. C.; Morrill, T. C. Spectrophotometric Identification of Organic Compounds, 5th ed.; Wiley: New York, 1991; pp 183 and 185. (b) Berger, S.; Braun, S.; Kalinowski, H.-O. NMR Spectroscopy of Non-Metallic Elements; John Wiley: Chichester, 1997. (41) Connor, J. A.; Kennedy, R. J.; Dawes, H. M.; Horsthame, M. B.; Walker, N. P. C. J. Chem. Soc., Perkin Trans. 2 1990, 203-207. (42) Schilf, W.; Kamien´ski, B.; Dziembowska, T. J. Mol. Struct. 2002, 602-603, 41-47.

Benzo-Annulated N-Salicylideneanilines TABLE 2. Tautomeric Equilibrium Constants (KT ) [NH]/[OH] ) [δ(C1) - 150 ppm]/[183 ppm - δ(C1)]) and Percentages of the NH Forms Present in the Equilibrium Mixture of Compounds 1-20 Dissolved in DMSO-d6 and CDCl3 (in italic), at 303 K no.

KT

NH form (%)a

1

0.39 0.51 1.74 1.71 0.22 0.26 2.47 2.10 9.68 17.64 0.43 0.48 1.99 0.22 3.93 11.22 2.81 4.00 0.08 0.00 5.63 7.42 10.60 164 3.13 3.14 6.40 6.67 14.42 79.49

28 34 63.5 63 18 20 71 77.5 90.5 (87.0) 95 (88.6) 30 33 76.5 18 79.5 (77.1) 92 73.5 80 (74.0) 7.5 0 85 (81.3) 88 (81.3) 91.5 (95.8) 100 (96.9) 76 76 86.5 87 93.5 (94.8) 99 (96.1)

2 3 4 5 6 7 8 9 10 12 13 14 15 17 19 20 a

Data based on 1JNH values are given in parentheses.

17, 19, and 20 the 15NH signal can be seen between δ ) -158.3 and -250.5 ppm in DMSO-d6 and between -150.0 and -251.7 ppm in CDCl3 (Table 1), which shows that both OH and NH forms are present in their solutions. 1JN8/H8 values change from -92 to -39 Hz for the latter compounds. C7 in the 13C NMR spectra of N-salicylideneanilines 1-20 resonates in the ranges of δ ) 144.73-163.18 and 141.79162.63 ppm in DMSO-d6 and CDCl3, respectively (Table 1) (the 13C chemical shift of C7 of N-(3-hydroxy-4-pyridinemethylidene)aniline is 160.9 ppm27b). A comparison with the data in Table 1 shows that solutions of compounds 1, 3, 6, 8, and 13 contain an increasing amount of the OH tautomer. The signal of C1 for salicylideneanilines 1, 3, 6, 8, and 13 can be seen in the ranges of δ ) 152.41-159.95 and 150.11161.14 ppm in DMSO-d6 and CDCl3, respectively (Table 1). The 13C chemical shift of C1 is believed to be the most sensitive parameter depending on the relative population of the tautomers.43 Increasing amount of the NH tautomer (compounds 2, 4, 5, 7, 9, 10, 12, 14, 15, 17, 19, and 20) shifts this signal to δ ) 170.95-181.07 and 170.81-182.80 ppm in DMSO-d6 and CDCl3, respectively (Table 1).21c,44,45 The 13C chemical shifts of C1 for the neat OH and NH forms, δ ) 155 and 180 ppm, respectively43,44 were earlier selected for use in calculation of tautomeric constants in solutions of N-salicylideneanilines. Since (43) Alarco´n, S. H.; Olivieri, A. C.; Sanz, D.; Claramunt, R. M.; Elguero, J. J. Mol. Struct. 2004, 705, 1-9. (44) Alarco´n, S. H.; Olivieri, A. C.; Gonza´les-Sierra, M. J. Chem. Soc., Perkin Trans. 2 1994, 1067-1070. (45) Alarco´n, S. H.; Olivieri, A. C.; Nordon, A.; Harris, R. H. J. Chem. Soc., Perkin Trans. 2 1996, 2293-2296.

for 13 δ(C1) < 155 ppm and for 15 δ(C1) > 180 ppm in DMSO-d6 and CDCl3, values of 150 and 183 ppm, respectively, were used by us to calculate KT ) [NH]/[OH] ) [δ(C1) 150 ppm]/[183 ppm - δ(C1)] (Table 1). Another method to calculate the equilibrium constants is to use the one-bond nitrogen-H-atom coupling constants. Amounts of the NH form, being equal to [1JNH/(-96 Hz)] × 100%21b and shown in Table 2, do not deviate significantly from those based on the 13C chemical shift of C1. Although the proton exchange between the OH and NH forms is fast on the NMR time-scale, changes in the composition of the tautomeric mixture also affect other spectral parameters, i.e., the chemical shifts of H7, H8/15, C6, C7, and N8 and the 3JH7/H8 coupling constants22a (see also Table 1). Although the amount of the NH form of N-(2-hydroxy-1-naphthylmethylidene)aniline 2 found in CDCl3, shown in Table 2, is comparable to that calculated by Alarco´n et al.,44 it is considerably higher than that found by Zhuo22a (chemical shifts of C1 were used in these evaluation procedures). The data in Table 2 show that chloroform solutions contain usually slightly more of the NH form than DMSO solutions. This shows that stabilization of the NH tautomer in the dipolar, hydrogen-bond acceptor solvent DMSO46 is more effective than in the less polar, weak hydrogen-bond donor chloroform46 (less stable N...H-O hydrogen bonds are usually stronger than N-H‚‚‚O ones17b,c,24a). The bond lengths of tautomeric forms were used to estimate the geometry-based aromaticity index HOMA (Harmonic Oscillator Model of Aromaticity)47 as defined in eq 1:

HOMA ) 1 -

1

n

∑ Ri(Ropt,i - Rj)2 n j)1

(1)

where n represents the total number of bonds in the molecule, Ri is a normalization constant (for CC, CO, and CN bonds RCC ) 257.7, RCO ) 157.38, and RCN ) 93.52, respectively), fixed to give HOMA ) 0 for a model nonaromatic system, e.g., the Kekule´ structure of benzene, and HOMA ) 1 for the system with all bonds equal to the optimal value Ropt,i, assumed to be realized for fully aromatic systems. For C-C bonds, Ropt,C-C ) 138.8 pm, for CN bonds Ropt,C-N ) 133.4 pm and for C-O is Ropt,C-O ) 126.5 pm. The higher the HOMA value, the more “aromatic” is the ring in question, and hence the more delocalized the π-electrons of the system. The position of the hydrogen atom in H-bonded fragments of compounds 1-20 determines the π-electron delocalization in all rings present in the molecule. This aspect is discussed now in more detail. Table 3 contains HOMA values for individual rings and quasirings except the cases where a spontaneous proton transfer in 3NH, 8NH, and 18NH during the geometry optimization precludes calculation of the HOMA values for these forms (extremely unstable species are automatically transformed into more stable systems in the Gaussian procedure of geometry optimization). As seen from the data in Table 3, the HOMA values for ring A vary in a substantial range from -0.28 (20NH with COMe as substituent in ring E) to 0.92 (for 1OH and 11OH with CO2Me as substituent at ring E). Variation in HOMA for the quasiring Q is less significant, but it still ranges from 0.29 for 18OH with COMe as substituent at ring E to 0.66 for 15OH with CO2Me as substituent at ring E. (46) Reichardt, Ch. SolVent and SolVent Effects in Organic Chemistry, 3rd ed.; Wiley-VCH: Weinheim, 2003. (47) Krygowski, T. M. J. Chem. Inf. Comput. Sci. 1993, 33, 70-78.

J. Org. Chem, Vol. 72, No. 15, 2007 5603

Gawinecki et al. TABLE 3. HOMA Values for N-Salicylideneanilines 1-20 and

TABLE 4. Selected Calculated (DFT(B3LYP)/6-31G(2d,p)) Bond

Their Tautomersa

Lengths [pm] as Well as Bond and Interplanar Anglesa [deg] in N-Salicylideneanilines 1-20 and Their Tautomers no./form C7-N8 C1-O15 C7N8C9 C7N8C9C14 C9C10C16O17

ring no./form

R

A

B

C

D

E

Q

Q′

1OH 1NH 2OH 2NH 3OH 4OH 4NH 5OH 5NH 6OH 6NH 7OH 7NH 8OH 9OH 9NH 10OH 10NH 11OH 11NH 12OH 12NH 13OH 13NH 14OH 14NH 15OH 15NH 16OH 16NH 17OH 17NH 18OH 19OH 19NH 20OH 20NH

H H H H H H H H H CONH2 CONH2 CONH2 CONH2 CONH2 CONH2 CONH2 CONH2 CONH2 CO2Me CO2Me CO2Me CO2Me CO2Me CO2Me CO2Me CO2Me CO2Me CO2Me COMe COMe COMe COMe COMe COMe COMe COMe COMe

0.92 0.44 0.65 0.12 0.74 0.70 0.14 0.35 -0.15 0.91 0.22 0.63 0.01 0.74 0.68 0.02 0.33 -0.19 0.92 0.28 0.64 -0.02 0.75 0.37 0.69 0.01 0.34 -0.26 0.92 0.24 0.64 -0.06 0.74 0.69 0.00 0.34 -0.28

0.83 0.90 0.88 0.91 0.83 0.91 0.88 0.92 0.83 0.91 0.88 0.94 0.83 0.91 0.88 0.92

0.83 0.92 0.90 0.94 0.84 0.93 0.90 0.94 0.84 0.93 0.90 0.92 0.83 0.93 0.90 0.94

0.76 0.75 0.76 0.49 0.75 -

0.98 0.98 0.98 0.98 0.98 0.98 0.98 0.98 0.98 0.95 0.91 0.95 0.94 0.96 0.95 0.94 0.95 0.94 0.95 0.94 0.94 0.93 0.95 0.95 0.94 0.93 0.94 0.93 0.94 0.92 0.93 0.91 0.94 0.93 0.91 0.93 0.91

0.47 0.59 0.58 0.61 0.31 0.59 0.63 0.63 0.70 0.50 0.47 0.60 0.54 0.33 0.62 0.54 0.67 0.60 0.48 0.50 0.60 0.51 0.32 0.47 0.62 0.53 0.66 0.59 0.48 0.48 0.58 0.48 0.29 0.59 0.52 0.65 0.58

-0.12 -0.04 -0.11 -0.07 -0.12 -0.11 -0.01 -0.10 0.00 0.05 0.11 0.04 0.13 0.05 0.05 0.03 0.14 0.04 0.14 -0.05 0.02 -0.02 0.04 -0.02 -0.04 0.09 -0.03 0.09

a HOMA values for extremely unstable forms (3NH, 8NH, and 18NH) are lacking (see Discussion).

These substantial changes need an interpretation. There is a dramatic difference in value of the mean HOMA for OH forms (HOMA ) 0.65) and NH forms (HOMA ) 0.05). Following the canonical structures shown in the tautomerization reaction (Scheme 2), the NH tautomer is characterized by an orthoquinoid form of ring A. This is supported by short C-O bonds for all systems with NH‚‚‚O hydrogen bonding: the mean CO bond length is 124.6 pm (Table 4). Following a well-known observation that any doubly bonded link of the substituent to the aromatic moiety decreases the aromaticity of the ring,48 one can see that the NH‚‚‚O hydrogen bond increases the aromaticity (48) Cyran´ski, M. K.; Krygowski, T. M.; Wisiorowski, M.; van Eikema Hommes, N. J. R.; Schleyer, P. v. R. Angew. Chem., Int. Ed. 1998, 37, 177-180.

5604 J. Org. Chem., Vol. 72, No. 15, 2007

1OH 1NH 2OH 2NH 3OH 4OH 4NH 5OH 5NH 6OH 6NH 7OH 7NH 8OH 9OH 9NH 10OH 10NH 11OH 11NH 12OH 12NH 13OH 13NH 14OH 14NH 15OH 15NH 16OH 16NH 17OH 17NH 18OH 19OH 19NH 20OH 20NH

129.0 132.9 129.6 133.5 128.8 129.4 133.6 129.8 133.8 128.8 133.5 129.4 134.4 128.6 129.2 134.5 129.6 134.8 128.8 134.1 129.4 134.6 128.6 132.9 129.2 134.7 129.7 134.9 128.9 134.3 129.3 134.9 128.5 129.2 134.8 129.6 135.0

133.6 126.2 132.9 125.6 134.0 133.1 125.2 132.6 125.2 133.1 125.3 132.4 124.6 133.6 132.5 124.0 132.0 123.9 133.4 124.6 132.6 124.2 133.8 125.9 132.6 124.0 132.1 123.9 133.5 124.5 132.7 124.2 134.0 132.9 123.8 132.2 123.7

121.18 128.64 121.13 127.69 121.19 121.44 128.30 121.33 128.24 122.03 126.08 121.71 125.62 121.92 122.24 125.95 121.79 125.60 121.13 124.82 120.94 124.71 121.07 124.54 121.51 125.03 121.20 124.74 120.57 124.79 121.02 124.77 121.82 120.98 125.17 121.01 124.86

35.67 0.03 -35.02 -14.35 -35.53 -33.99 -7.81 34.51 0.13 37.06 22.21 36.76 -18.01 36.38 35.41 -13.83 36.51 -15.00 45.44 23.63 -43.31 22.22 46.39 28.98 40.29 20.27 40.49 21.08 -45.98 -22.01 -46.69 -20.24 -50.44 -45.94 -19.59 -44.44 -20.52

-40.03 32.19 -39.35 -29.92 -39.89 -39.81 -24.65 -39.67 -22.96 8.10 -8.64 3.55 -7.53 10.29 -8.40 -10.70 -7.45 -11.15 -7.18 -12.13 7.72 5.71 -9.27 -16.73 -7.99 7.00 -2.47 6.99

a Data for extremely unstable forms (3NH, 8NH, and 18NH) are lacking (see Discussion).

of quasiring Q (mean HOMA 0.65 for OH forms and 0.62 for NH forms) and decreases aromatic character of ring A. Another aspect of the low aromaticity of ring A becomes more understandable if the systems with quasirings are grouped in a way to resemble benzenoid hydrocarbons. In the case of compounds 5, 10, 15, and 20 the system built up of rings A, B, C, and quasiring Q simulate triphenylene (three CH units in the molecule were replaced by the N‚‚‚H‚‚‚O moiety). The central ring in triphenylene has HOMA ) 0.11, whereas the mean HOMAs (ring A) for the OH and NH forms are equal to 0.34 and -0.22, respectively. Thus, compounds 5, 10, 15, and 20 are similar to triphenylene. Obviously, for NH systems the lowering of HOMA in ring A is enhanced by the abovementioned influence of the quinoidal structure because of shortening of the C-O bonds. However, a general view is in line with recent studies of π-electron systems in which the CHCHCH fragment in triphenylene was replaced by OHO8,9 or OLiO.9,49 In the case of OH forms, this effect is weaker, but still observable; the mean HOMA for ring A is 0.34, which is closer to the value observed in triphenylene for the central ring (0.11) than a typical value for the peripheral rings B, C, D, or E (∼0.9). For 2, 7, 12, and 17 as well as 4, 9, 14, and 19 somewhat similar observations are found. In these cases the molecules are (49) Krygowski, T. M.; Zachara, J. E.; Moszyn´ski, R. J. Chem. Inf. Model. 2005, 45, 1837-1841.

Benzo-Annulated N-Salicylideneanilines

built up of rings A, B, and Q (2, 7, 12, and 17) and A, C, and Q (4, 9, 14, and 19). All these compounds resemble phenanthrene in which CHCHCH is replaced by an OHN fragment. The low value of HOMA for ring A in the NH forms (0.01 for 2, 7, 12, and 17, and 0.04 for 4, 9, 14, and 19) is again due to a substantial shortening of the C-O bond associated with an increased contribution of the quinoid-like canonical structure for NH forms. On the other hand, this effect is much weaker in OH forms. Thus, HOMA for ring A is 0.64 for 2, 7, 12, and 17, and 0.69 for 4, 9, 14, and 19. However, an analogy of the above-discussed moieties to phenanthrene is obvious: the HOMA value for the central ring in phenanthrene (0.47) and HOMA values for A ring in these compounds are closer to this value than to the usual HOMA values for the peripheral rings (∼0.9). In compounds 3, 8, 13, and 18 as well as 6, 11, and 16, where interesting moieties are built up of A, D, Q and A and Q rings, respectively, the influence of the quinoid-like structure for systems with a NH‚‚‚O hydrogen bond is obvious, i.e., the HOMA values for ring A are low (0.37 and 0.30, respectively). However, for OH tautomers HOMA varies between 0.7 and 0.9, imitating the values for a typical polyacene. The intramolecular hydrogen bond in salicyl- and 3-hydroxynaphthalene-2-carbaldehydes is weaker as that the monoenol of malonaldehyde, but the aromaticity of the benzene ring that annulates this system in salicyl- and 3-hydroxynaphthalene-2carbaldehydes is relatively high.8,9 On the other hand, although the RAHB hydrogen bond in the OH forms 2, 4, and 5 is strong, the aromaticity of the benzene ring A in these tautomers is relatively low (similar relations were observed for 2-hydroxynaphthalene-1-carbaldehyde, 1-hydroxynaphthalene-2-carbaldehyde, and 10-hydroxyphenanthrene-9-carbaldehyde8,9). The quasiring Q′ is not aromatic in OH tautomers 6-20; the respective HOMA values are low which shows that the intramolecular hydrogen bond between H8 and the carbonyl oxygen in R5 is not formed. It is well-known that the “anilinic” benzene ring in benzylideneanilines is considerably twisted with respect to the azomethine moiety (there is no conjugation between these two moieties).50 The constancy of the HOMA values for ring E in the OH and NH tautomers (Table 3) suggests that, despite involving the lone electron pair on nitrogen atom in the intramolecular hydrogen bond, this ring is also considerably twisted in compounds 1-20. Calculations (Table 4) show that this is the case mainly for the OH tautomers. N-Salicylideneaniline and N-(2-hydroxy-3-naphthylmethylidene)aniline resemble 2-phenacylpyridine and 3-phenacylisoquinoline (solutions and gas phase of all these compounds contain the enolimine forms15a-c,37f,g,i,51). On the other hand, the enaminone form is present in solution of N-(2-hydroxy-1naphthylmethylidene)aniline, N-(1-hydroxy-2-naphthyl-methylidene)aniline, N-(10-hydroxy-9-phenanthrylmethylidene)aniline, 1-phenacylisoquinoline, 2-phenacylquinoline, and 6-phenacylphenanthridine.15c Although N-salicylidene derivatives of orthoC(dO)X substituted anilines are structurally similar to the respective derivatives of dibenzo-cis,cis-bis(β-formylvinyl)-

amine, only the former compounds in solution are in equilibrium with the respective tautomeric monoenol form. Geometry optimization shows that the C1-O15 bond lengths in the OH and NH forms change form 132.0 to 134.0 pm and from 123.7 to 126.2 pm, respectively (Table 4). N8 and H15 are located very close to each other in 5OH (158.7 pm), which shows that from this point of view 5OH resembles 5NH. On the other hand, the distance N8‚‚‚H15 in 3OH, 8OH, 13OH, and 18OH is usually above 178 pm, which is typical for the OH form. Since O15 and H8 are located very close to each other in 1NH (161.2 pm), 1NH again very much resembles 1OH. On the other hand, the O15‚‚‚H8 distance in 9NH, 10NH, 14NH, 15NH, 19NH, and 20NH is usually close to 192 pm (these are the typical NH forms). Values of the C7N8C9 bond angle (Table 4) in the OH (120.57 - 122.24 deg) and NH forms (124.554 - 128.64 deg) prove that these tautomers contain the pyridine-like and pyrrolelike sp2 hybridized N8. One can expect that the “anilinic” benzene ring in the NH forms to almost coplanar with the C7N8(H8)C9 moiety. Indeed, the C7N8C9C14 angles in these tautomers are not large (Table 4). The C1C6C7N8 interplanar angles change from -5.30° (15OH) to 6.94° (20OH) for the OH forms and from ca -9° (10NH, 20NH) to 8.29° (15NH) for the NH forms (Table 4). Twisting around the C1-C6 bond is less significant: the O15C1C6C7 interplanar angle is equal to -1.96-1.11° for the OH forms and -11.85 (15NH) -ca 13° (10NH and 20NH) for the NH forms. The values of both C1C6C7N8 and O15C1C6C7 angles prove that the quasiring Q in these tautomers is relatively planar. The C9C10C16O17 values (Table 4) show that substituent C(dO)X is significantly twisted with respect to the benzene ring (this especially refers to the CONH2 group in OH forms). Calculated energies (Table 5) show that in vacuum, and especially in DMSO solution, the NH form is more stable than the OH form only for 10, 15, and 20. Indeed, the percentage of NH form in solutions of these derivatives of 10-hydroxyphenanthrene-9-carbaldehyde is the highest. In other cases the OH form is more stable: this refers especially to the 3-hydroxynaphthalene-2-carbaldehyde derivatives 3, 8, and 18 (their solutions contain only a minimum amount of the NH form). Moreover, it can be seen that dissolution in DMSO stabilizes both NH and OH tautomers (Table 5). One should keep in mind that earlier estimates11,12,20,21 have shown that the NH forms, i.e., 2-[(phenylamino)methylene]cyclohexa-3,5-dien-1-ones, are more stable than the OH forms, i.e., N-salicylideneamines. The energies of the tautomers are expected to be related to the composition of the tautomeric mixture. Indeed, there is a linear relationship between the percentage of NH form in DMSO solution (Table 2) and the relative energy of this tautomer (Table 5) in DMSO solution [NH(%) ) 1.60Erel + 86.45, correlation coefficient r ) 0.974 for 17 data points]. Analysis of the NMR spectra has shown that the OH′ form (Scheme 3) is not present in solution. This finding was also proved by theoretical calculations: a spontaneous proton transfer observed during their geometry optimization results in formation of the more stable OH and NH forms.

(50) (a) Ebara, N. Bull. Chem. Soc. Jpn. 1960, 33, 534-539. (b) 1960, 33, 540-543. (c) Scheuer-Lamalle, B.; Durocher, G. Can. J. Spectrosc. 1976, 21, 165-171. (d) Ezumi, K.; Nakai, H.; Sakata, S.; Nishikida, K.; Shiro, M.; Kubota, T. Chem. Lett. 1974, 1393-1398. (51) Martiskainen, O.; Gawinecki, R.; Os´miałowski, B.; Pihlaja, K. Eur. J. Mass Spectrom. 2006, 12, 25-29.

Conclusions Enolimines are the products of proton transfer in β-aminoR,β-unsaturated carbonyl systems, shortly called enaminones. 2-[(Phenylamino)methylene]cyclohexa-3,5-dien-1-one (being in J. Org. Chem, Vol. 72, No. 15, 2007 5605

Gawinecki et al. TABLE 5. Calculated Energies in Vacuum and in DMSO Solution (in italics) for N-Salicylideneanilines 1-20 and Their Tautomers no. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Eabs(NH)a [Hartree]

Eabs(OH)a [Hartree]

Erel(OH)b,c [kJ/mol]

-630.425434 -630.440351 -783.694263 -783.708911 d

-630.440640 -630.452028 -783.701409 -783.713746 -783.701158 -783.714867 -783.705308 -783.717902 -936.968937 -936.982419 -798.796139 -798.818874 -952.057213 -952.080862 -952.056498 -952.081684 -952.061248 -952.085013 -1105.325085 -1105.349747 -857.842969 -857.856877 -1011.103649 -1011.118600 -1011.103633 -1011.119888 -1011.107452 -1011.122601 -1164.371307 -1164.387337 -782.746034 -782.760558 -936.006963 -936.022526 -936.006754 -936.023689 -936.010729 -936.026388 -1089.274495 -1089.291068

-39.93 -30.66 -18.76 -12.70 -15.24 -8.95 -5.08 -0.45 -40.64 -31.51 -17.77 -12.35 -14.12 -8.74 -0.02 3.30 -39.67 -30.14 -13.82 -7.99 -65.06 -50.52 -9.44 -3.63 4.53 8.71 -39.04 -29.87 -14.12 -8.88 -8.55 -2.90 6.04 9.90

-783.699504 -783.714495 -936.967001 -936.982248 -798.780660 -798.806872 -952.050447 -952.076160 d -952.055869 -952.081683 -1105.325079 -1105.351003 -857.827859 -857.845396 -1011.098385 -1011.115558 -1011.078852 -1011.100646 -1011.103858 -1011.121218 -1164.373033 -1164.390653 -782.731164 -782.749180 -936.001586 -936.019143 d -936.007471 -936.025283 -1089.276794 -1089.294838

a Absolute. b Relative. c Positive and negative value of E show that the rel NH and OH form is more stable, respectively. d Data for extremely unstable forms (3NH, 8NH and 18NH) are lacking (see Discussion).

fact a benzo-annulated β-aminoacroleine) is the tautomer of N-salicylideneaniline (these species are shortly called NH and OH forms, respectively). Although ortho-C(dO)X groups in their molecules should enable the formation of additional tautomers stabilized by bifurcated intramolecular hydrogen bonds, 1H, 13C, and 15N NMR spectra show that such species are not present in solution of the parent N-salicylidene-orthoC(dO)X-anilines and their various benzo-annulated derivatives. The stabilization of the NH tautomer in the dipolar, hydrogenbond acceptor solvent DMSO is more effective than in the less polar, weak hydrogen-bond donor chloroform. The values of the geometry based aromaticity index HOMA (Harmonic Oscillator Model of Aromaticity) show that π-elektron delocalization in the individual rings of the molecule is affected by formation of the quinoid structure for tautomers that contain a NH‚‚‚O intramolecular hydrogen bond. The moderate aromatic character of the quasiring in both OH and NH tautomers for all compounds studied proves that both N‚‚‚H-O and N-H‚‚‚O hydrogen bonds in these forms are strong. On the other hand, low HOMA values for another quasiring in the molecule show that there is only one intramolecular hydrogen bond in both OH and NH tautomers (there is no bifurcation). Since the Schiff 5606 J. Org. Chem., Vol. 72, No. 15, 2007

bases studied and the respective ortho-hydroxyaldehydes are isoelectronic compounds, benzo-annulation affects similarly their aromatic character. High HOMA values show that in all cases studied the OH form is more stable. Calculated energies support the validity of this conclusion: the NH form has a lower energy only in two cases. Thus, it is obvious that neither HOMA values nor calculated energies are the absolute criterion, that allows determine the dominating tautomer. On the other hand, both these parameters correctly show the trend of changes in molecular topology on tautomeric preferences. Experimental Section Salicylaldehyde and 2-hydroxynaphthalene-1-carbaldehyde were commercial products. Synthetic methods for 1-hydroxynaphthalene2-carbaldehyde52 (mp 52-54 °C, lit. mp 57-58 °C,53 54 °C,54 5355 °C,52 58-59 °C,55 53.2-54.2 °C6), and 3-hydroxynaphthalene2-carbaldehyde56 (mp 97.5-99.5 °C, lit. mp 99-100 °C,53,57 100102 °C,58 97-98 °C,4a 96.3-96.8 °C,6 98-99 °C56) were previously described. 10-Hydroxyphenanthrene-9-carbaldehyde (mp 134-137 °C, lit. mp 133 °C,54 136.7-137.5 °C,7 127-128 °C20b) was obtained6 from 9-methoxyphenanthrene, which, in turn, was prepared from 9-bromophenanthrene.59 (Benzo)salicylidene Derivatives of Aniline, Anthranilamide, Methyl Anthranilate and o-Aminoacetophenone (1-15, 17, 19, and 20). A solution of (benzo)hydroxybenzaldehyde (4 mmol) and aniline, anthranilamide, methyl anthranilate, or o-aminoacetophenone (4 mmol) in 96% ethanol (10 mL) was left for few hours at room temperature (0.5-1 h reflux was necessary for reactions with methyl anthranilate and o-aminoacetophenone). The crude product precipitated from the reaction mixture was recrystallized from 96% ethanol. Mp’s (°C) of the obtained crystalline Schiff bases are as follows: 1 (49-50, lit. 49.6-50.022a), 2 (42-45, lit. 91.5-92.3,22a 10060), 3 (163-164, lit. 157-158,57 160-16261), 4 (67-68, lit. 9660), 5 (142-144, lit. 133-13420b), 6 (160-165/decomp, lit. 165/ (52) Hamada, Ch. J. Chem. Soc. Jpn., Pure Chem. Sect. 1952, 73, 47; Chem. Abstr. 1953, 47, 995a. (53) Narasimhan, N. S.; Mali, R. S. Tetrahedron 1975, 31, 1005-1009. (54) Ziegler, G.; Haug, E.; Frey, W.; Kantlehner, W. Z. Naturforsch. 2001, B56, 1178-1187. (55) Shoesmith, J. B.; Haldane, J. J. Chem. Soc. 1924, 125, 2405-2407. (56) Khorana, M. L.; Pandit, S. Y. J. Indian Chem. Soc. 1963, 40, 789793. (57) Przhiyalgovskaya, N. M.; Lavrishcheva, L. N.; Mondodoev, G. T.; Belov, V. N. Zh. Obshch. Khim. 1961, 31, 2321-2325. (58) Coll, G.; Morey, J.; Costa, A.; Saa´, J. M. J. Org. Chem. 1988, 53, 5345-5348. (59) Bacon, R. G. R.; Rennison, S. C. Chem. Ind. (London) 1966, 812. (60) Matskevich, T. N.; Shanter, L. A.; Shanter, Yu. A.; Trailina, Ye. P.; Savich, I. A.; Spitsyn, I. Dokl. Akad. Nauk SSSR, Ser. Khim. 1972, 205, 593-595. (61) Fernandez-G., J. M.; Enriquez, R. G.; Reynolds, W. F.; Yu, M. Magn. Reson. Chem. 1994, 32, 180-181. (62) (a) Smith, T. A. K.; Stephen, H. Tetrahedron 1957, 1, 38-44. (b) Pater, R. J. Heterocycl. Chem. 1971, 8, 699-702. (63) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, revision D.01; Gaussian, Inc.: Wallingford, CT, 2004.

Benzo-Annulated N-Salicylideneanilines decomp62), 7 (194-196 (202/decomp32), 8 (160-165), 9 (222226), 10 (236-237), 12 (95-96), 13 (93-97), 14 (166-168), 15 (204-205), 17 (179-182.5), 19 (148-150) and 20 (229-231). Satisfactory analytical data ((0.3% for C, H, and N) were obtained for all new compounds. The conditions for recording the NMR spectra were described earlier.15c Calculations have been performed with the Gaussian 03 software package.63 Each tautomer has been optimized with a DFT(B3LYP)/ 6-31G(2d,p) level of theory. Vibrational frequencies were calculated at the same level to make sure that the geometry is in a minimum (no imaginary frequencies). The relative energies for tautomeric forms both in vacuum and in solution (PCM model of solvation)

have been calculated with MP2/6-31G(2df,2p) level of theory (single point calculations).

Acknowledgment. We are very much indebted to the Academic Computer Centre CYFRONET, AGH Cracow, for supply of computer time and programs, and to Ministry of Higher Education for grant N204 121 32/3121. Supporting Information Available: Molecular modeling coordinates and NMR spectra of compounds 8-10, 12-15, 17, 19, 20. This material is available free of charge via the Internet at http://pubs.acs.org. JO070454F

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