Influence of Bond Fixation in Benzo-AnnulatedN-Salicylideneanilines and Theirortho-C(dO)X Derivatives

(X ) CH3, NH2, OCH3) on Tautomeric Equilibria in Solution

Ryszard Gawinecki,*,† Agnieszka Kuczek,† Erkki Kolehmainen,‡ Borys Osmiałowski,†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 JyVaskyla, Finland,

and Department of Chemistry, UniVersity of Warsaw, Pasteura 1, PL-02-093 Warsaw, Poland

gawiner@utp.edu.pl

ReceiVed March 22, 2007

1H, 13C, and 15N NMR spectra show that anortho-C(dO)X group present in the molecules ofN-salicylideneanthranilamide (X) NH2), methylN-salicylideneanthranilate (X) OCH3), N-salicylidene-o-aminoacetophenone (X) CH3), and their benzo analogues have only a minor effect on the tautomericOH/NH-equilibrium in solution. Only two of three possible tautomers were detected. Lability of theabsent 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-annulatedN-salicylideneanilines.The population of each species in the tautomeric mixture was found to be inversely proportional to itsenergy. Application of the geometry-based aromaticity index HOMA shows that the effectiveness of theπ-electron delocalization in different rings in the molecule depends mostly on the position of benzo-annulation. Both the NH‚‚‚O and N‚‚‚HO hydrogen bonds present in theNH and OH tautomers,respectively, increase the aromaticity of the quasirings H-O-CdC-CdN and OdC-CdC-N-H anddecrease the aromatic character of the fused benzene ring. These results seem to be reliable whenN-salicylideneanilines studied are compared with naphthalene and their benzo-annulated derivatives, i.e.,phenanthrene, anthracene, and triphenylene. An analysis of the effectiveness ofπ-electron delocalizationconfirms that in all cases studied, theOH form is more stable. Although the HOMA values and calculatedenergies are not a criterion that allows determination of the dominating tautomer, both of these parameterscorrectly 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 andC2-C3 bond lengths are different. The bonds in anthracene,phenanthrene, and in many other polycyclic benzenoid hydro-

carbons are also nonequivalent. Since addition to phenanthreneand its oxidation and reduction take place at the 9,10-positionsunder conditions at which the C1-C2 bonds in naphthaleneand anthracene are either inert or much less reactive, the C9-C10 bond in the former compound has much more olefiniccharacter than the latter bonds.1

Although there is only one vicinally disubstituted benzenederivative, two adjacent substituents in the naphthalene deriva-tive can occupy the 1/2, 2/1, or 2/3 positions. Further, thearomaticity of a substituted benzene ring is expected to be

* Author to whom correspondence should be addressed. Tel:+48 523749070, fax:+48 52 3749005.

† University of Technology and Life Sciences.‡ University of Jyvaskyla.§ University of Warsaw.

5598 J. Org. Chem.2007, 72, 5598-560710.1021/jo070454f CCC: $37.00 © 2007 American Chemical Society

Published on Web 06/23/2007

dependent on the character of the attached groups.2 The strengthof chelation in vicinally disubstituted naphthalene derivativesdepends on the multiplicity of the bond joining the ring carbonatoms holding the two substituents.3 Metal chelates derived from3-hydroxy-2-naphthaldehyde are less stable than those from its1,2- or 2,1-isomers.4 In naphthalene this behavior was attributedto the greater double bond character of the C1-C2 bond whencompared to the C2-C3 bond.4a Analysis of the ultravioletspectra of hydroxynaphthaldehydes supports this conclusion.5

IR spectra show that intramolecular hydrogen bonds in 1,2- and2,1-hydroxyformyl-, hydroxyacetyl-, and hydroxy(methoxycar-bonyl)naphthalenes are almost identical by strength6 and arestronger than those in 2,3-substituted isomers.6 Correspondinghydrogen bonds in 9,10-hydroxyformyl-, hydroxyacetyl-, andhydroxy(methoxycarbonyl)phenanthrenes were shown to be thestrongest interactions of this type yet encountered in simplearomatic compounds.7

Although aromaticity of the substituted benzene ring insalicyl- and 3-hydroxynaphthalene-2-carbaldehydes is relativelyhigh,8 the intramolecular hydrogen bond in these compoundsis weaker than that in the monoenol of malonaldehyde.8,9 Onthe other hand, the hydrogen bonds in 2-hydroxynaphthalene-1-carbaldehyde, 1-hydroxynaphthalene-2-carbaldehyde, and 10-hydroxyphenanthrene-9-carbaldehyde are much stronger thanthat in the monoenol of malonaldehyde.8,9 It is noteworthy thatthe HO-C-C-CdO fragment in these compounds is consider-ably more aromatic than those in salicyl- and 3-hydroxynaph-thalene-2-carbaldehydes.8,9 On the other hand, the substitutedbenzene ring in 2-hydroxynaphthalene-1-carbaldehyde, 1-hy-droxynaphthalene-2-carbaldehyde, and 10-hydroxyphenanthrene-9-carbaldehyde is less aromatic than those in salicyl- and3-hydroxynaphthalene-2-carbaldehydes.8,9

Chelation in the respectiveortho-disubstituted benzenes hasan intermediate strength between 1,2- (or 2,1-) and 2,3-disubstituted naphthalenes.6 On the basis of evidence derivedboth from chemical reactions and IR spectra, the highly olefinicnature of the C9-C10 bond in phenanthrene was confirmed.7

Wave numbers of the CdO stretching band,6,7 NMR chemicalshifts of the hydroxy H-atoms,10aand vicinal coupling constantsfor the hydrogens on two carbons of the bond (3JH,H)10b,c foro-hydroxy derivatives of formyl-, acetyl-, and methoxycarbo-nylbenzenes, naphthalenes, and phenanthrenes depend on mul-tiplicity of the bond joining the ring carbon atoms holding thesubstituents. On the other hand, not entirely concordant conclu-sions on the bond fixation in naphthalene can be drawn from a

comparison of melting points and critical solution temperaturesof the 1,2-, 2,1-, and 2,3-hydroxyacetylnaphthalenes,4b theacidities ofo-hydroxynaphthaldehydes11 ando-chloronaphthoicacids,12 and the measured bond lengths for the naphthalenederivatives.13

Since proton transfer in numerous aromatic systems involvesa migration of the double bond,14 one should observe greatchanges in the bond lengths for different tautomers. As aconsequence, some tautomers of certain aromatic compoundsmay lose their aromaticity. That is why studies on tautomerismmay tell much about bond fixation in aromatic compounds.

Several studies15 show that proton transfer inâ-amino-R,â-unsaturated carbonyl systems, shortly called enaminones, enablesthese compounds to equilibriate with enolimines and, sometimes,with ketiminones (Scheme 1).16 Both enaminone and enolimineforms can be stabilized by an intramolecular hydrogen bondnot only in the solid state but also in nonpolar solvents.15e

Although a N‚‚‚H-O intramolecular hydrogen bond isstronger than a N-H‚‚‚O hydrogen bond, tautomeric speciesstabilized by the latter interaction are usually of lower energy.17

(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, 3482-3512.

(4) (a) Calvin, M.; Melchior, N. C.J. Am. Chem. Soc.1948, 70, 3273-3275. (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, 5241-

5248.(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.

(11) Vargas, V.; Amigo, L.J. Chem. Soc., Perkin Trans. 22001, 1124-1129.

(12) Dziembowska, T.; Jagodzin´ska, E.; Rozwadowski, Z.; Kotfica, M.J. Mol. Struct.2001, 598, 229-234.

(13) Robertson, J. M.Proc. R. Soc. London1933, 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. 22000, 2185-2191. (b)Kolehmainen, E.; Os´miałowski, B.; Krygowski, T. M.; Kauppinen, R.;Nissinen, M.; Gawinecki, R.J. Chem. Soc., Perkin Trans. 22000, 1259-1266. (c) Gawinecki, R.; Kolehmainen, E.; Loghmani-Khouzani, H.;Osmiałowski, B.; Lovasz, T.; Rosa, P.Eur. J. Org. Chem.2006, 2817-2824. (d) Go´mez-Sa´nchez, A.; Paredes-Leo´n, R.; Campora, 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) Dabrowski, 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.Tetrahedron1968, 24, 5655-5664. (k) Dabrowski, 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.; VonPhilipsborn, W.Org. Magn. Reson.1981, 17, 306-310. (n) Kashima, Ch.;Yamamoto, M.; Sugiyama, N.J. Chem. Soc., C1970, 111-114. (o)Kashima, Ch.; Aoyama, H.; Yamamoto, Y.; Nishio, T.J. Chem. Soc., PerkinTrans. 21975, 665-670. (p) Zhuo, J.-C.Magn. Reson. Chem.1998, 36,565-572. (q) Fustero, S.; De la Torre, M. G.; Jofre´, V.; Carlon, 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.

SCHEME 1

Benzo-Annulated N-Salicylideneanilines

J. Org. Chem, Vol. 72, No. 15, 2007 5599

â-Amino-R,â-unsaturated carbonyl compounds are capable ofundergoing spontaneously conformational and configurationalisomerizations in solution.15f-q,18 Enaminone tautomers of3-aminoacroleins, which are stabilized by intramolecular hy-drogen bonds, and their open forms are favored in nonpolarand polar solvents, respectively.15d Benzo-annulation is knownto affect the stability of enaminones and their tautomers. Therelative energy of the tautomers was found to be governedmainly by a change in the degree of heterocycle aromaticityupon hydrogen transfer, but the strength of the intramolecularhydrogen bond provides also some contribution.19 Thus, onlyenolimine and ketiminone forms were detected when R1,R2 )benzo (Scheme 1).15aFurther, benzo-annulation of the pyridinering in molecules of these compounds at 3,4- and/or 5,6-positions 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, werefound to be in equilibrium with the usually less stable20

enolimine derivatives, i.e.,N-salicylideneamines.11,12,21 Polarsolvents, low temperatures, and benzo-annulation both inpositions 2,3 and 4,5 favor theNH form.21c,22TheNH tautomeris the only form present in the crystalline state ofN-(2-hydroxy-1-naphthylmethylidene)aniline21c and the major form detectedin solutions of N-(10-hydroxy-9-phenanthrylmethylidene)-aniline.20b The proton transfer betweenN-salicylideneanilinesand their enaminone tautomeric forms can take place not onlyin solution but also in the condensed phase.23 Since thecompound under such conditions represents a superposition ofthe OH andNH tautomers,24 each bond length measured is aweighted average of the corresponding bond lengths in thesespecies according to their molar ratios. It is therefore concludedthat the population of theNH tautomer increases with loweringthe temperature. Analysis of the molecular geometry shows thatthe enaminone has a zwitterionic character (it is predominantlyquinoid in the gas phase).17a,24bStabilization of theNH form in

the crystalline state results primarily from intermolecularhydrogen bonding.24b Changes in the population of theNH andOH tautomers in the crystalline state and in solution withvariation of temperature are responsible for the thermochromicproperties of numerous salicylideneanilines.17a,20a,24b

As suggested by Gilli et al.,25 Schiff bases derived fromaromatico-hydroxyaldehydes show synergism between strengthof the hydrogen bond and degree of delocalization ofπ electrons(however, no dependence between delocalization of theπelectrons and the H-bond strength was observed in the crystallinestate26). The composition of a tautomeric mixture depends onthe stability of the respective tautomers which, in turn, is relatedto the π-electron delocalization in the molecule and to thestrength of the intramolecular hydrogen bond15a,22a,25(N‚‚‚H-Ohydrogen bonds are stronger than N-H‚‚‚O bonds17b,c,24a).

Imines of salicylaldehyde are simple models of the respectivepyridoxal derivatives which play an important role in enzymatictransformations ofR-amino acids27 (all these compounds containthe hydroxy group in theortho position with respect to themethylideneamine function). The presence of an intramolecularhydrogen bond is essential for the enzymatic properties of Schiffbases of pyridoxal phosphate andR-amino acids. The proton-transfer process from oxygen to nitrogen atom in thesemolecules is the first step of the catalytic cycle.28 Sirtinol, 2-[(2-hydroxynaphthalen-1-ylmethylene)amino]-N-(1-phenylethyl)-benzamide, the best known inhibitor of the SIRT2 (silentinformation regulator) which deacetylatesR-tubulin and par-ticipates in controlling the mitotic exit in the cell cycle,29 isanother Schiff base of the same type, which additionally containsthe CONHCH(CH3)Ph group. Benzo-annulation is expected tohave a stabilizing effect on selected tautomers ofN-salicylide-neaniline. On the other hand,ortho-C(dO)X substituents in suchcompounds should enable the formation of additional tautomericspecies. Thus, it would be interesting to clarify how these twoeffects influence the tautomeric equilibria in solutions ofN-salicylideneanilines. Aims of the present paper are (i) to showhow the position of benzo-annulation inN-salicylideneanilineaffects the tautomeric equilibria in solution (one would askwhich tautomer, i.e., more or less aromatic, is more stable), and(ii) to clarify the capability of theo-carbonyl group in the“anilinic” benzene ring of these compounds to attract the acidicH-atom.

Results and Discussion

TheN-salicylideneanilines1-20presented in Scheme 2 wereobtained by simple condensation of the respective aldehyde withsubstituted anilines (see Experimental Section). Because of thehigh tendency of some compounds to hydrolyze, we were notable to prepare methylN-salicylideneanthranilate (11), N-salicylidene-o-aminoacetophenone (16, known compound30), and

(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. A2002, 106, 11956-11962.

(18) Dabrowski, J.Spectrochim. Acta1963, 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, 2442-

2446. (b) Alarco´n, S. H.; Olivieri, A. C.; Labadie, G. R.; Cravero, R. M.;Gonzales-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, 991-994. (d) Galic, N.; Cimerman, Z.; Tomis´ic, V. Anal. Chim. Acta1997, 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) Krol-Starzomska, I.; Rospenk, M.; Rozwadowski, Z.; Dzi-embowska, 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. 22000, 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.

(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.; Dziem-bowska, T.Tetrahedron1999, 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.Tetrahedron2005, 61, 145-154. (c) Spies, M. A.; Toney,M. D. Biochemistry2003, 42, 5099-5107. (d) Malashkevitch, V. N.; Toney,M. D.; Jansonius, J. N.Biochemistry1993, 32, 13451-13462. (e) Zhou,X.; Toney, M. D.Biochemistry1999, 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.

Gawinecki et al.

5600 J. Org. Chem., Vol. 72, No. 15, 2007

N-(3-hydroxy-2-naphthylmethylidene)-o-aminoacetophenone (18),even by modifying the preparative methods described in theExperimental Section as well as that described in the literature30

(the tendency of other compounds, e.g.,8, to react with tracesof water present in the NMR solvents is also noteworthy).Unfortunately, literature melting points of some methylN-salicylideneanthranilates, which were previously obtained fromthe respective aldehyde and methyl anthranilate,31 are notdisclosed. The formation of different polymorphic crystallineforms and liquid crystal properties of some compounds obtainedare probably responsible for the wide melting point ranges andtheir divergence with literature data (Experimental Section). TheNMR spectra, however, confirm that the compounds obtainedby us are those expected to be formed in reactions of aldehydeswith anilines.

In DMSO solution,N-salicylideneanthranilamide (OH form)is in equilibrium with the respectiveNH tautomer (Scheme 3,X ) NH2).32 One should realize, however, that another

enolimine form, i.e., theOH′ tautomer (Scheme 3), can alsocontribute to the tautomeric equilibrium. The tautomerism ofbenzo-annulatedN-salicylideneanthranilamides has not beenstudied earlier.

Tautomeric equilibria have not been studied either for alkylN-salicylideneanthranilates,21f N-salicylidene-o-aminoacetophe-nones,30 or their benzo analogues. These compounds and theirtautomers are in fact dibenzo derivatives ofcis,cis-bis(â-formylvinyl)amine {(2Z,6Z,4E-4-aza-7-hydroxyhepta-2,4,6-trienal} (A in Scheme 4), being found to be stabilized bybifurcated hydrogen bonds (no respective (2Z)-3-[((1Z)-3-oxoprop-1-enyl)-amino]prop-2-enal tautomeric form, denotedas B in Scheme 4, was detected in solution).33 On the otherhand, bis(o-formylphenyl)amine, which is also stabilized by abifurcated hydrogen bond,34 and N-salicylidene-o-amino-acetophenone are isomeric derivatives of bis(â-formylvinyl)-amine that differ from each other only by position of annulation.

The presence of additional functions in the molecule mayplay a crucial role in stabilization of the tautomers. X-ray studiesshow thatN-salicylideneanthranilic acid in the crystalline stateis an intermediate between the enolimine and enaminone form.35

The dimer formed is stabilized both by intra- and intermolecularhydrogen bonds. Only theOH form is present in solution (nodimerization takes place there).35

Although all three different tautomers presented in Scheme3 are stabilized by a bifurcated intramolecular hydrogen bondof RAHB type,36 their relative stability is not known. Becauseof bifurcation, both theNH andOH forms should be more stablethan those tautomers ofN-salicylideneaniline which are stabi-lized only by a single intramolecular hydrogen bond.

Multinuclear magnetic resonance spectroscopic techniqueshave provided an excellent tool to investigate tautomericequilibria quantitatively.15a,b,37It has been reported that proto-nation-caused chemical shift changes of the ring nitrogen atomin aza aromatic compounds are very large.38 Consequently,15NNMR spectroscopy provides valuable information on theirtautomerism.39 One should keep in mind that only one averagesignal for each nucleus appears in the NMR spectrum of

(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.

(32) Christie, R. M.; Moss, S.J. Chem. Soc., Perkin Trans. 11985,2779-2783.

(33) (a) Dabrowski, J.; Swistun, Z. J. Chem. Soc., B1971, 818-821.(b) Dabrowski, J.; Swistun, Z.Tetrahedron1973, 29, 2261-2267.

(34) Dabrowski, J.; Swistun, Z.; Dabrowska, U.; Sˆwistun, Z.Tetrahedron1973, 29, 2257-2260.

(35) Ligtenbarg, A. G. J.; Hage, R.; Meetsma, A.; Feringa, B. L.J. Chem.Soc., Perkin Trans. 21999, 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.

SCHEME 2 SCHEME 3

SCHEME 4

Benzo-Annulated N-Salicylideneanilines

J. Org. Chem, Vol. 72, No. 15, 2007 5601

tautomeric mixtures when the proton exchange between indi-vidual forms is fast on the NMR time-scale.37eThus, in the casewhen basic centers in the tautomers are the strongly electro-negative oxygen and nitrogen atoms, integration of the1H NMRsignals is useless for calculation of the contribution of the speciespresent in solution.

Since there is almost no influence of benzo-annulation onthe 13C chemical shift of carbonyl carbon atom C16 in the13CNMR spectra of amide (6-10), ester (12-15), and ketone (17,19, and20) derivatives ofN-salicylideneanilines (Table 1), theOH′ tautomeric form (Scheme 3) seems to be absent in solution(the carbonyl13C chemical shifts for the compounds studied,shown in Table 1, are typical for the primary amides, esters,

and ketones40). This conclusion is also verified by the narrowrange of the15N chemical shift (from-270.9 to-262.1 ppm)of the amide nitrogen atom for compounds6-10. Both 15Nchemical shifts and1JNH (from -89.5 to-88.0 Hz) for thesecompounds are typical for primary amides.40b

The 1H NMR signal of H7 ofN-salicylideneanilines1-20can be seen atδ ) 8.72-9.64 and 8.13-9.31 ppm in DMSO-d6 and CDCl3, respectively (Table 1). It is a singlet forcompounds1, 3, 6, 8, and 13. Splitting due to considerablecontribution of theNH tautomer transforms this signal to adoublet (sometimes to a broadened singlet). The3J(H7,H8)coupling constants, equal to 5.2-12.1 Hz, are typical forenaminones22a). The1H NMR signals of the acidic H-atom H8/H15 of N-salicylideneanilines1-20, seen atδ ) 12.13-15.76and 12.19-15.48 ppm in DMSO-d6 and CDCl3, respectively(Table 1), is upfield shifted as compared with that of therespective H-atom in the1H NMR spectra ofcis,cis-bis(â-acylvinyl)amines.33a Its multiplicity is of the same type as thatof H7 (coupling constantsJ is equal to 5.2-12.0 and 6.5-12.0Hz in DMSO-d6 and CDCl3, respectively). Significant upfieldshift of this signal in the spectra of compounds1, 3, 6, 8, and13, as compared to other compounds studied, suggests anincreasing amount of theOH form15j,22a(the broadened singletof the hydroxy H-atom ofN-(3-hydroxy-4-pyridinemethylidene)-aniline in CDCl3, which contains exclusively theOH form,appears atδ ) 12.76 ppm27b). Splitting of the H8 signal provesthat theNH form is present in solution. If one assumes that forthe pureNH form 1JNH ) 89 Hz, the tautomeric equilibriumconstant in solution of9 (1JNH ) 74 Hz) can be calculated fromequationKT ) [89 - 1J(H,N)]/1J(H,N).22c KT is equal to 0.20which shows that there exists 83% of theNH form in DMSOsolution of9.

The signal of N8 in the15N NMR spectra ofN-salicylide-neanilines1, 3, 6, 8, and13 can be seen betweenδ ) -78.0and-85.3 ppm, both in DMSO-d6 and CDCl3 (Table 1). Thesevalues are typical for theOH form41 (the chemical shift of N8in the NMR spectrum ofN-(3-hydroxy-4-pyridinemethylidene)-aniline is-67.5 ppm27b). The multiplicity of this signal (singlet)confirms that theOH form is the major contributor in solutionsof these compounds.41,42 On the other hand, in the15N NMRspectra ofN-salicylideneanilines2, 4, 5, 7, 9, 10, 12, 14, 15,

(37) (a) Witanowski, M.; Stefaniak, L.; Webb, G. A.Ann. Rep. NMRSpectrosc.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)Osmiałowski, B.; Kolehmainen, E.; Gawinecki, R.Chem.-Eur. J. 2003,9, 2710-2716. (j) Gawinecki, R.; Kolehmainen, E.; Kuczek, A.; Pihlaja,K.; Osmiałowski, B.J. Phys. Org. Chem.2005, 18, 737-742.

(38) Levy, G. C.; Lichter R. L.Nitrogen-15 Nuclear Magnetic ResonanceSpectroscopy; 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.Spectrophoto-metric Identification of Organic Compounds, 5th ed.; Wiley: New York,1991; pp 183 and 185. (b) Berger, S.; Braun, S.; Kalinowski, H.-O.NMRSpectroscopy 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. 21990, 203-207.

(42) Schilf, W.; Kamien´ski, B.; Dziembowska, T.J. Mol. Struct.2002,602-603, 41-47.

TABLE 1. Selected1H, 13C, and 15N NMR Chemical Shifts (δ) andCoupling Constants (Hz) (in parentheses) ofN-Salicylideneanilines1-20 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 13.08 159.22 118.04 162.42 - -85.38.63 13.27 161.14 117.23 162.63 - -85.0

2 9.64 15.76 170.95 108.37 155.24 - -158.3(5.2) (5.2)9.31 15.48 170.81 108.75 154.40 - -150.0

3 9.13 12.58 156.03 121.39 163.18 - -78.48.80 12.74 156.73 121.22 162.51 - -78.5

4 8.95 14.86 173.50 110.30 156.56 - -189.7(6.6) (6.4)8.48 14.88 172.34 110.92 156.09 - -173.7(8.2) (8.2)

5 9.31 15.06 179.91 104.77 148.08 - -234.2(11.5) (11.5) (-83.5)8.84 14.84 181.23 105.63 146.36 - -235.4(11.3) (11.0) (-85.1)

6 8.86 12.49 159.95 119.66 162.96 168.85-85.3(8.7) (8.7)8.60 12.19 160.75 119.04 165.28 168.29-85.4

7 9.42 14.32 171.98 108.78 153.96 169.01c8 9.02 12.13 155.86 122.01 162.92 168.88-79.09 8.72 14.49 176.31 110.79 153.43 168.93-214.5

(10.0) (10.1) (-74.0)10 9.03 14.72 180.30 105.94 145.65 169.04-245.1

(12.0) (12.1)12 9.42 15.18 174.33 108.86 152.48 166.08-184.9

(7.1) (7.1)9.06 15.22 176.40 109.27 149.63 166.43-192.3(7.5) (7.1) (-71.0)

13 9.03 12.40 152.41 118.77 165.89 165.89d8.70 12.53 156.67 119.23 162.81 166.49-78.0

14 8.79 14.63 178.02 111.01 152.41 165.89-233.3(10.5) (10.5) (-78.0)8.13 14.75 179.08 111.69 150.12 166.49-221.3(9.9) (9.5) (-78.0)

15 9.10 14.86 181.07 106.58 144.95 165.94-250.5(11.8) (11.8) (-92.0)8.72 14.87 182.80 107.87 141.97 166.63-250.5(11.9) (12.0) (-93.0)

17 9.35 15.00 175.00 108.86 151.81 200.02-191.5(7.7) (7.7)9.07 15.05 175.03 109.38 150.85 199.64-182.6(6.5) (6.5)

19 8.72 14.59 178.54 111.05 151.82 200.14-229.7(10.6) (10.9)8.59 14.77 178.70 111.85 150.12 199.66-219.9(8.0) (8.0)

20 9.06 14.86 180.86 106.71 144.73 200.13-248.8(12.1) (12.0) (-91.0)8.72 15.02 182.59 108.11 141.79 199.62-251.7(11.9) (11.4) (-92.3)

a Doublet or broadened singlet;3J(1H,1H) values are given in parentheses.b 1J(1H,15N) values are given in parentheses.c Not observed.d Insufficientsolubility.

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5602 J. Org. Chem., Vol. 72, No. 15, 2007

17, 19, and20 the15NH signal can be seen betweenδ ) -158.3and-250.5 ppm in DMSO-d6 and between-150.0 and-251.7ppm in CDCl3 (Table 1), which shows that bothOH andNHforms are present in their solutions.1JN8/H8 values change from-92 to -39 Hz for the latter compounds.

C7 in the13C NMR spectra ofN-salicylideneanilines1-20resonates in the ranges ofδ ) 144.73-163.18 and 141.79-162.63 ppm in DMSO-d6 and CDCl3, respectively (Table 1)(the13C chemical shift of C7 ofN-(3-hydroxy-4-pyridinemeth-ylidene)aniline is 160.9 ppm27b). A comparison with the datain Table 1 shows that solutions of compounds1, 3, 6, 8, and13 contain an increasing amount of theOH tautomer.

The signal of C1 for salicylideneanilines1, 3, 6, 8, and13can be seen in the ranges ofδ ) 152.41-159.95 and 150.11-161.14 ppm in DMSO-d6 and CDCl3, respectively (Table 1).The13C chemical shift of C1 is believed to be the most sensitiveparameter depending on the relative population of the tau-tomers.43 Increasing amount of theNH tautomer (compounds2, 4, 5, 7, 9, 10, 12, 14, 15, 17, 19, and20) shifts this signal toδ ) 170.95-181.07 and 170.81-182.80 ppm in DMSO-d6 andCDCl3, respectively (Table 1).21c,44,45The 13C chemical shiftsof C1 for the neatOH andNH forms,δ ) 155 and 180 ppm,respectively43,44 were earlier selected for use in calculation oftautomeric constants in solutions ofN-salicylideneanilines. Since

for 13 δ(C1) < 155 ppm and for15 δ(C1) > 180 ppm inDMSO-d6 and CDCl3, values of 150 and 183 ppm, respectively,were used by us to calculateKT ) [NH]/[OH] ) [δ(C1) -150 ppm]/[183 ppm- δ(C1)] (Table 1).

Another method to calculate the equilibrium constants is touse the one-bond nitrogen-H-atom coupling constants. Amountsof the NH form, being equal to [1JNH/(-96 Hz)] × 100%21b

and shown in Table 2, do not deviate significantly from thosebased on the13C chemical shift of C1. Although the protonexchange between theOH andNH forms is fast on the NMRtime-scale, changes in the composition of the tautomeric mixturealso affect other spectral parameters, i.e., the chemical shifts ofH7, H8/15, C6, C7, and N8 and the3JH7/H8 coupling constants22a

(see also Table 1). Although the amount of theNH form ofN-(2-hydroxy-1-naphthylmethylidene)aniline2 found in CDCl3,shown in Table 2, is comparable to that calculated by Alarco´net 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 containusually slightly more of theNH form than DMSO solutions.This shows that stabilization of theNH tautomer in the dipolar,hydrogen-bond acceptor solvent DMSO46 is more effective thanin the less polar, weak hydrogen-bond donor chloroform46 (lessstable N...H-O hydrogen bonds are usually stronger thanN-H‚‚‚O ones17b,c,24a).

The bond lengths of tautomeric forms were used to estimatethe geometry-based aromaticity index HOMA (Harmonic Oscil-lator Model of Aromaticity)47 as defined in eq 1:

wheren represents the total number of bonds in the molecule,Ri is a normalization constant (for CC, CO, and CN bondsRCC

) 257.7,RCO ) 157.38, andRCN ) 93.52, respectively), fixedto give HOMA ) 0 for a model nonaromatic system, e.g., theKekule structure of benzene, and HOMA) 1 for the systemwith all bonds equal to the optimal valueRopt,i, assumed to berealized for fully aromatic systems. For C-C bonds,Ropt,C-C

) 138.8 pm, for CN bondsRopt,C-N ) 133.4 pm and for C-Ois Ropt,C-O ) 126.5 pm. The higher the HOMA value, the more“aromatic” is the ring in question, and hence the moredelocalized theπ-electrons of the system.

The position of the hydrogen atom in H-bonded fragmentsof compounds1-20 determines theπ-electron delocalizationin all rings present in the molecule. This aspect is discussednow in more detail. Table 3 contains HOMA values forindividual rings and quasirings except the cases where aspontaneous proton transfer in3NH, 8NH, and18NH duringthe geometry optimization precludes calculation of the HOMAvalues for these forms (extremely unstable species are automati-cally transformed into more stable systems in the Gaussianprocedure of geometry optimization). As seen from the data inTable 3, the HOMA values for ring A vary in a substantial rangefrom -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, butit still ranges from 0.29 for18OH with COMe as substituent atring E to 0.66 for15OH with CO2Me as substituent at ring E.(43) Alarcon, S. H.; Olivieri, A. C.; Sanz, D.; Claramunt, R. M.; Elguero,

J. J. Mol. Struct.2004, 705, 1-9.(44) Alarcon, S. H.; Olivieri, A. C.; Gonza´les-Sierra, M.J. Chem. Soc.,

Perkin Trans. 21994, 1067-1070.(45) Alarcon, S. H.; Olivieri, A. C.; Nordon, A.; Harris, R. H.J. Chem.

Soc., Perkin Trans. 21996, 2293-2296.

(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.

TABLE 2. Tautomeric Equilibrium Constants (KT ) [NH]/[OH] )[δ(C1) - 150 ppm]/[183 ppm- δ(C1)]) and Percentages of the NHForms Present in the Equilibrium Mixture of Compounds 1-20Dissolved in DMSO-d6 and CDCl3 (in italic), at 303 K

no. KT NH form (%)a

1 0.39 280.51 34

2 1.74 63.51.71 63

3 0.22 180.26 20

4 2.47 712.10 77.5

5 9.68 90.5 (87.0)17.64 95 (88.6)

6 0.43 300.48 33

7 1.99 76.58 0.22 189 3.93 79.5 (77.1)10 11.22 9212 2.81 73.5

4.00 80 (74.0)13 0.08 7.5

0.00 014 5.63 85 (81.3)

7.42 88 (81.3)15 10.60 91.5 (95.8)

164 100 (96.9)17 3.13 76

3.14 7619 6.40 86.5

6.67 8720 14.42 93.5 (94.8)

79.49 99 (96.1)

a Data based on1JNH values are given in parentheses. HOMA ) 1 -1

n∑j)1

n

Ri(Ropt,i - Rj)2 (1)

Benzo-Annulated N-Salicylideneanilines

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

These substantial changes need an interpretation. There is adramatic difference in value of the mean HOMA forOH forms(HOMA ) 0.65) andNH forms (HOMA ) 0.05). Followingthe canonical structures shown in the tautomerization reaction(Scheme 2), theNH tautomer is characterized by anortho-quinoid form of ring A. This is supported by short C-O bondsfor all systems with NH‚‚‚O hydrogen bonding: the mean CObond length is 124.6 pm (Table 4). Following a well-knownobservation that any doubly bonded link of the substituent tothe aromatic moiety decreases the aromaticity of the ring,48 onecan see that the NH‚‚‚O hydrogen bond increases the aromaticity

of quasiring Q (mean HOMA 0.65 forOH forms and 0.62 forNH forms) and decreases aromatic character of ring A. Anotheraspect of the low aromaticity of ring A becomes moreunderstandable if the systems with quasirings are grouped in away to resemble benzenoid hydrocarbons. In the case ofcompounds5, 10, 15, and20 the system built up of rings A, B,C, and quasiring Q simulate triphenylene (three CH units inthe molecule were replaced by the N‚‚‚H‚‚‚O moiety). Thecentral ring in triphenylene has HOMA) 0.11, whereas themean HOMAs (ring A) for theOH andNH forms are equal to0.34 and-0.22, respectively. Thus, compounds5, 10, 15, and20 are similar to triphenylene. Obviously, for NH systems thelowering of HOMA in ring A is enhanced by the above-mentioned influence of the quinoidal structure because ofshortening of the C-O bonds. However, a general view is inline with recent studies ofπ-electron systems in which theCHCHCH fragment in triphenylene was replaced by OHO8,9

or OLiO.9,49 In the case ofOH forms, this effect is weaker, butstill observable; the mean HOMA for ring A is 0.34, which iscloser to the value observed in triphenylene for the central ring(0.11) than a typical value for the peripheral rings B, C, D, orE (∼0.9).

For 2, 7, 12, and17 as well as4, 9, 14, and19 somewhatsimilar observations are found. In these cases the molecules are

(48) Cyranski, M. K.; Krygowski, T. M.; Wisiorowski, M.; van EikemaHommes, N. J. R.; Schleyer, P. v. R.Angew. Chem., Int. Ed. 1998, 37,177-180.

(49) Krygowski, T. M.; Zachara, J. E.; Moszyn´ski, R. J. Chem. Inf.Model.2005, 45, 1837-1841.

TABLE 3. HOMA Values for N-Salicylideneanilines 1-20 andTheir Tautomersa

ring

no./form R A B C D E Q Q′

1OH H 0.92 - - - 0.98 0.47 -1NH H 0.44 - - - 0.98 0.59 -2OH H 0.65 0.83 - - 0.98 0.58 -2NH H 0.12 0.90 - - 0.98 0.61 -3OH H 0.74 - - 0.76 0.98 0.31 -4OH H 0.70 - 0.83 - 0.98 0.59 -4NH H 0.14 - 0.92 - 0.98 0.63 -5OH H 0.35 0.88 0.90 - 0.98 0.63 -5NH H -0.15 0.91 0.94 - 0.98 0.70 -6OH CONH2 0.91 - - - 0.95 0.50 -0.126NH CONH2 0.22 - - - 0.91 0.47 -0.047OH CONH2 0.63 0.83 - - 0.95 0.60 -0.117NH CONH2 0.01 0.91 - - 0.94 0.54 -0.078OH CONH2 0.74 - - 0.75 0.96 0.33 -0.129OH CONH2 0.68 - 0.84 - 0.95 0.62 -0.119NH CONH2 0.02 - 0.93 - 0.94 0.54 -0.0110OH CONH2 0.33 0.88 0.90 - 0.95 0.67 -0.1010NH CONH2 -0.19 0.92 0.94 - 0.94 0.60 0.0011OH CO2Me 0.92 - - - 0.95 0.48 0.0511NH CO2Me 0.28 - - - 0.94 0.50 0.1112OH CO2Me 0.64 0.83 - - 0.94 0.60 0.0412NH CO2Me -0.02 0.91 - - 0.93 0.51 0.1313OH CO2Me 0.75 - - 0.76 0.95 0.32 0.0513NH CO2Me 0.37 - - 0.49 0.95 0.47 0.0514OH CO2Me 0.69 - 0.84 - 0.94 0.62 0.0314NH CO2Me 0.01 - 0.93 - 0.93 0.53 0.1415OH CO2Me 0.34 0.88 0.90 - 0.94 0.66 0.0415NH CO2Me -0.26 0.94 0.92 - 0.93 0.59 0.1416OH COMe 0.92 - - - 0.94 0.48 -0.0516NH COMe 0.24 - - - 0.92 0.48 0.0217OH COMe 0.64 0.83 - - 0.93 0.58 -0.0217NH COMe -0.06 0.91 - - 0.91 0.48 0.0418OH COMe 0.74 - - 0.75 0.94 0.29 -0.0219OH COMe 0.69 - 0.83 - 0.93 0.59 -0.0419NH COMe 0.00 - 0.93 - 0.91 0.52 0.0920OH COMe 0.34 0.88 0.90 - 0.93 0.65 -0.0320NH COMe -0.28 0.92 0.94 - 0.91 0.58 0.09

a HOMA values for extremely unstable forms (3NH, 8NH, and18NH)are lacking (see Discussion).

TABLE 4. Selected Calculated (DFT(B3LYP)/6-31G(2d,p)) BondLengths [pm] as Well as Bond and Interplanar Anglesa [deg] inN-Salicylideneanilines 1-20 and Their Tautomers

no./form C7-N8 C1-O15 C7N8C9 C7N8C9C14 C9C10C16O17

1OH 129.0 133.6 121.18 35.67 -1NH 132.9 126.2 128.64 0.03 -2OH 129.6 132.9 121.13 -35.02 -2NH 133.5 125.6 127.69 -14.35 -3OH 128.8 134.0 121.19 -35.53 -4OH 129.4 133.1 121.44 -33.99 -4NH 133.6 125.2 128.30 -7.81 -5OH 129.8 132.6 121.33 34.51 -5NH 133.8 125.2 128.24 0.13 -6OH 128.8 133.1 122.03 37.06 -40.036NH 133.5 125.3 126.08 22.21 32.197OH 129.4 132.4 121.71 36.76 -39.357NH 134.4 124.6 125.62 -18.01 -29.928OH 128.6 133.6 121.92 36.38 -39.899OH 129.2 132.5 122.24 35.41 -39.819NH 134.5 124.0 125.95 -13.83 -24.6510OH 129.6 132.0 121.79 36.51 -39.6710NH 134.8 123.9 125.60 -15.00 -22.9611OH 128.8 133.4 121.13 45.44 8.1011NH 134.1 124.6 124.82 23.63 -8.6412OH 129.4 132.6 120.94 -43.31 3.5512NH 134.6 124.2 124.71 22.22 -7.5313OH 128.6 133.8 121.07 46.39 10.2913NH 132.9 125.9 124.54 28.98 -8.4014OH 129.2 132.6 121.51 40.29 -10.7014NH 134.7 124.0 125.03 20.27 -7.4515OH 129.7 132.1 121.20 40.49 -11.1515NH 134.9 123.9 124.74 21.08 -7.1816OH 128.9 133.5 120.57 -45.98 -12.1316NH 134.3 124.5 124.79 -22.01 7.7217OH 129.3 132.7 121.02 -46.69 5.7117NH 134.9 124.2 124.77 -20.24 -9.2718OH 128.5 134.0 121.82 -50.44 -16.7319OH 129.2 132.9 120.98 -45.94 -7.9919NH 134.8 123.8 125.17 -19.59 7.0020OH 129.6 132.2 121.01 -44.44 -2.4720NH 135.0 123.7 124.86 -20.52 6.99

a Data for extremely unstable forms (3NH, 8NH, and18NH) are lacking(see Discussion).

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

built up of rings A, B, and Q (2, 7, 12, and17) and A, C, andQ (4, 9, 14, and19). All these compounds resemble phenan-threne in which CHCHCH is replaced by an OHN fragment.The low value of HOMA for ring A in theNH forms (0.01 for2, 7, 12, and17, and 0.04 for4, 9, 14, and19) is again due toa substantial shortening of the C-O bond associated with anincreased contribution of the quinoid-like canonical structurefor NH forms. On the other hand, this effect is much weaker inOH forms. Thus, HOMA for ring A is 0.64 for2, 7, 12, and17, and 0.69 for4, 9, 14, and19. However, an analogy of theabove-discussed moieties to phenanthrene is obvious: theHOMA value for the central ring in phenanthrene (0.47) andHOMA values for A ring in these compounds are closer to thisvalue than to the usual HOMA values for the peripheral rings(∼0.9).

In compounds3, 8, 13, and18as well as6, 11, and16, whereinteresting moieties are built up of A, D, Q and A and Q rings,respectively, the influence of the quinoid-like structure forsystems with a NH‚‚‚O hydrogen bond is obvious, i.e., theHOMA values for ring A are low (0.37 and 0.30, respectively).However, forOH tautomers HOMA varies between 0.7 and0.9, imitating the values for a typical polyacene.

The intramolecular hydrogen bond in salicyl- and 3-hydroxy-naphthalene-2-carbaldehydes is weaker as that the monoenolof malonaldehyde, but the aromaticity of the benzene ring thatannulates this system in salicyl- and 3-hydroxynaphthalene-2-carbaldehydes is relatively high.8,9 On the other hand, althoughthe RAHB hydrogen bond in theOH forms2, 4, and5 is strong,the aromaticity of the benzene ring A in these tautomers isrelatively low (similar relations were observed for 2-hydroxy-naphthalene-1-carbaldehyde, 1-hydroxynaphthalene-2-carbal-dehyde, and 10-hydroxyphenanthrene-9-carbaldehyde8,9). Thequasiring Q′ is not aromatic inOH tautomers6-20; therespective HOMA values are low which shows that theintramolecular hydrogen bond between H8 and the carbonyloxygen in R5 is not formed.

It is well-known that the “anilinic” benzene ring in ben-zylideneanilines is considerably twisted with respect to theazomethine moiety (there is no conjugation between these twomoieties).50 The constancy of the HOMA values for ring E inthe OH and NH tautomers (Table 3) suggests that, despiteinvolving the lone electron pair on nitrogen atom in theintramolecular hydrogen bond, this ring is also considerablytwisted in compounds1-20. Calculations (Table 4) show thatthis is the case mainly for theOH tautomers.

N-Salicylideneaniline andN-(2-hydroxy-3-naphthylmethylide-ne)aniline resemble 2-phenacylpyridine and 3-phenacylisoquino-line (solutions and gas phase of all these compounds containthe enolimine forms15a-c,37f,g,i,51). On the other hand, theenaminone form is present in solution ofN-(2-hydroxy-1-naphthylmethylidene)aniline,N-(1-hydroxy-2-naphthyl-methyl-idene)aniline,N-(10-hydroxy-9-phenanthrylmethylidene)aniline,1-phenacylisoquinoline, 2-phenacylquinoline, and 6-phenacyl-phenanthridine.15c AlthoughN-salicylidene derivatives ofortho-C(dO)X substituted anilines are structurally similar to therespective derivatives of dibenzo-cis,cis-bis(â-formylvinyl)-

amine, only the former compounds in solution are in equilibriumwith the respective tautomeric monoenol form.

Geometry optimization shows that the C1-O15 bond lengthsin theOH andNH forms change form 132.0 to 134.0 pm andfrom 123.7 to 126.2 pm, respectively (Table 4). N8 and H15are located very close to each other in5OH (158.7 pm), whichshows that from this point of view5OH resembles5NH. Onthe other hand, the distance N8‚‚‚H15 in 3OH, 8OH, 13OH,and 18OH is usually above 178 pm, which is typical for theOH form. Since O15 and H8 are located very close to eachother in 1NH (161.2 pm),1NH again very much resembles1OH. On the other hand, the O15‚‚‚H8 distance in9NH, 10NH,14NH, 15NH, 19NH, and20NH is usually close to 192 pm(these are the typicalNH forms).

Values of the C7N8C9 bond angle (Table 4) in theOH(120.57- 122.24 deg) andNH forms (124.554- 128.64 deg)prove that these tautomers contain the pyridine-like and pyrrole-like sp2 hybridized N8. One can expect that the “anilinic”benzene ring in theNH forms to almost coplanar with the C7N8-(H8)C9 moiety. Indeed, the C7N8C9C14 angles in thesetautomers are not large (Table 4).

The C1C6C7N8 interplanar angles change from-5.30°(15OH) to 6.94° (20OH) for the OH forms and fromca -9°(10NH, 20NH) to 8.29° (15NH) for the NH forms (Table 4).Twisting around the C1-C6 bond is less significant: theO15C1C6C7 interplanar angle is equal to-1.96-1.11° for theOH forms and-11.85 (15NH) -ca 13° (10NH and20NH) fortheNH forms. The values of both C1C6C7N8 and O15C1C6C7angles prove that the quasiring Q in these tautomers is relativelyplanar. The C9C10C16O17 values (Table 4) show that sub-stituent C(dO)X is significantly twisted with respect to thebenzene ring (this especially refers to the CONH2 group inOHforms).

Calculated energies (Table 5) show that in vacuum, andespecially in DMSO solution, theNH form is more stable thantheOH form only for 10, 15, and20. Indeed, the percentage ofNH form in solutions of these derivatives of 10-hydroxyphenan-threne-9-carbaldehyde is the highest. In other cases theOH formis more stable: this refers especially to the 3-hydroxynaphtha-lene-2-carbaldehyde derivatives3, 8, and 18 (their solutionscontain only a minimum amount of theNH form). Moreover,it can be seen that dissolution in DMSO stabilizes bothNHand OH tautomers (Table 5). One should keep in mind thatearlier estimates11,12,20,21have shown that theNH forms, i.e.,2-[(phenylamino)methylene]cyclohexa-3,5-dien-1-ones, are morestable than theOH forms, i.e.,N-salicylideneamines.

The energies of the tautomers are expected to be related tothe composition of the tautomeric mixture. Indeed, there is alinear relationship between the percentage ofNH form in DMSOsolution (Table 2) and the relative energy of this tautomer (Table5) in DMSO solution [NH(%) ) 1.60Erel + 86.45, correlationcoefficient r ) 0.974 for 17 data points].

Analysis of the NMR spectra has shown that theOH′ form(Scheme 3) is not present in solution. This finding was alsoproved by theoretical calculations: a spontaneous proton transferobserved during their geometry optimization results in formationof the more stableOH andNH forms.

Conclusions

Enolimines are the products of proton transfer inâ-amino-R,â-unsaturated carbonyl systems, shortly called enaminones.2-[(Phenylamino)methylene]cyclohexa-3,5-dien-1-one (being in

(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.

Benzo-Annulated N-Salicylideneanilines

J. Org. Chem, Vol. 72, No. 15, 2007 5605

fact a benzo-annulatedâ-aminoacroleine) is the tautomer ofN-salicylideneaniline (these species are shortly calledNH andOH forms, respectively). Althoughortho-C(dO)X groups intheir molecules should enable the formation of additionaltautomers stabilized by bifurcated intramolecular hydrogenbonds,1H, 13C, and15N NMR spectra show that such speciesare not present in solution of the parentN-salicylidene-ortho-C(dO)X-anilines and their various benzo-annulated derivatives.The stabilization of theNH tautomer in the dipolar, hydrogen-bond acceptor solvent DMSO is more effective than in the lesspolar, weak hydrogen-bond donor chloroform. The values ofthe geometry based aromaticity index HOMA (HarmonicOscillator Model of Aromaticity) show thatπ-elektron delo-calization in the individual rings of the molecule is affected byformation of the quinoid structure for tautomers that contain aNH‚‚‚O intramolecular hydrogen bond. The moderate aromaticcharacter of the quasiring in bothOH and NH tautomers forall compounds studied proves that both N‚‚‚H-O and N-H‚‚‚Ohydrogen bonds in these forms are strong. On the other hand,low HOMA values for another quasiring in the molecule showthat there is only one intramolecular hydrogen bond in bothOH andNH tautomers (there is no bifurcation). Since the Schiff

bases studied and the respectiveortho-hydroxyaldehydes areisoelectronic compounds, benzo-annulation affects similarly theiraromatic character. High HOMA values show that in all casesstudied theOH form is more stable. Calculated energies supportthe validity of this conclusion: theNH form has a lower energyonly in two cases. Thus, it is obvious that neither HOMA valuesnor calculated energies are the absolute criterion, that allowsdetermine the dominating tautomer. On the other hand, boththese parameters correctly show the trend of changes inmolecular topology on tautomeric preferences.

Experimental Section

Salicylaldehyde and 2-hydroxynaphthalene-1-carbaldehyde werecommercial products. Synthetic methods for 1-hydroxynaphthalene-2-carbaldehyde52 (mp 52-54 °C, lit. mp 57-58 °C,53 54 °C,54 53-55 °C,52 58-59 °C,55 53.2-54.2°C6), and 3-hydroxynaphthalene-2-carbaldehyde56 (mp 97.5-99.5°C, lit. mp 99-100°C,53,57100-102°C,58 97-98°C,4a96.3-96.8°C,6 98-99°C56) were previouslydescribed. 10-Hydroxyphenanthrene-9-carbaldehyde (mp 134-137°C, lit. mp 133 °C,54 136.7-137.5 °C,7 127-128 °C20b) wasobtained6 from 9-methoxyphenanthrene, which, in turn, wasprepared 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) andaniline, anthranilamide, methyl anthranilate, oro-aminoacetophe-none (4 mmol) in 96% ethanol (10 mL) was left for few hours atroom temperature (0.5-1 h reflux was necessary for reactions withmethyl anthranilate ando-aminoacetophenone). The crude productprecipitated from the reaction mixture was recrystallized from 96%ethanol. Mp’s (°C) of the obtained crystalline Schiff bases are asfollows: 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.Tetrahedron1975, 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, 789-

793.(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.Tetrahedron1957, 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.Gaussian03, revision D.01; Gaussian, Inc.: Wallingford, CT, 2004.

TABLE 5. Calculated Energies in Vacuum and in DMSO Solution(in italics) for N-Salicylideneanilines 1-20 and Their Tautomers

no.Eabs(NH)a

[Hartree]Eabs(OH)a

[Hartree]Erel(OH)b,c

[kJ/mol]

1 -630.425434 -630.440640 -39.93-630.440351 -630.452028 -30.66

2 -783.694263 -783.701409 -18.76-783.708911 -783.713746 -12.70

3 d -783.701158 --783.714867 -

4 -783.699504 -783.705308 -15.24-783.714495 -783.717902 -8.95

5 -936.967001 -936.968937 -5.08-936.982248 -936.982419 -0.45

6 -798.780660 -798.796139 -40.64-798.806872 -798.818874 -31.51

7 -952.050447 -952.057213 -17.77-952.076160 -952.080862 -12.35

8 d -952.056498 --952.081684 -

9 -952.055869 -952.061248 -14.12-952.081683 -952.085013 -8.74

10 -1105.325079 -1105.325085 -0.02-1105.351003 -1105.349747 3.30

11 -857.827859 -857.842969 -39.67-857.845396 -857.856877 -30.14

12 -1011.098385 -1011.103649 -13.82-1011.115558 -1011.118600 -7.99

13 -1011.078852 -1011.103633 -65.06-1011.100646 -1011.119888 -50.52

14 -1011.103858 -1011.107452 -9.44-1011.121218 -1011.122601 -3.63

15 -1164.373033 -1164.371307 4.53-1164.390653 -1164.387337 8.71

16 -782.731164 -782.746034 -39.04-782.749180 -782.760558 -29.87

17 -936.001586 -936.006963 -14.12-936.019143 -936.022526 -8.88

18 d -936.006754 --936.023689 -

19 -936.007471 -936.010729 -8.55-936.025283 -936.026388 -2.90

20 -1089.276794 -1089.274495 6.04-1089.294838 -1089.291068 9.90

a Absolute.b Relative.c Positive and negative value of Erel show that theNH andOH form is more stable, respectively.d Data for extremely unstableforms (3NH, 8NH and18NH) are lacking (see Discussion).

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5606 J. Org. Chem., Vol. 72, No. 15, 2007

decomp62), 7 (194-196 (202/decomp32), 8 (160-165), 9 (222-226),10 (236-237),12 (95-96), 13 (93-97), 14 (166-168),15(204-205), 17 (179-182.5),19 (148-150) and20 (229-231).Satisfactory analytical data ((0.3% for C, H, and N) were obtainedfor all new compounds.

The conditions for recording the NMR spectra were describedearlier.15c

Calculations have been performed with the Gaussian 03 softwarepackage.63 Each tautomer has been optimized with a DFT(B3LYP)/6-31G(2d,p) level of theory. Vibrational frequencies were calculatedat the same level to make sure that the geometry is in a minimum(no imaginary frequencies). The relative energies for tautomericforms 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 theAcademic Computer Centre CYFRONET, AGH Cracow, forsupply of computer time and programs, and to Ministry ofHigher Education for grant N204 121 32/3121.

Supporting Information Available: Molecular modeling co-ordinates and NMR spectra of compounds8-10, 12-15, 17, 19,20. This material is available free of charge via the Internet athttp://pubs.acs.org.

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