Influence of bond fixation in benzo-annulated N-salicylideneanilines and their ortho-C(=O)X derivatives (X = CH3, NH2, OCH 3) on tautomeric equilibria in solution

Article abstract of DOI:10.1021/jo070454f

(Chemical Equation Presented) ¹H, ¹³C, and ¹⁵N NMR spectra show that an ortho-C(=O)X group present in the molecules of N-salicylideneanthranilamide (X = NH₂), methyl N-salicylideneanthranilate (X = OCH₃), N-salicylidene-o- 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-C=C-C=N and O=C-C=C-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.

Full text of DOI:10.1021/jo070454f

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
gawiner@utp.edu.pl
ReceiVed March 22, 2007
1H, 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-salicylidene-
o-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 benzo-
annulation. 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
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 C9-
C10 bond in the former compound has much more olefinic
character than the latter bonds.1
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-
Although there is only one vicinally disubstituted benzene
derivative, two adjacent substituents in the naphthalene deriva-
tive can occupy the 1/2, 2/1, or 2/3 positions. Further, the
aromaticity of a substituted benzene ring is expected to be
* 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.
10.1021/jo070454f CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/23/2007
5598
J. Org. Chem. 2007, 72, 5598-5607

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(methoxycar-
bonyl)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
SCHEME 1
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-hydroxynaphthalene-
1-carbaldehyde, 1-hydroxynaphthalene-2-carbaldehyde, and 10-
hydroxyphenanthrene-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 consider-
ably more aromatic than those in salicyl- and 3-hydroxynaph-
thalene-2-carbaldehydes.8,9 On the other hand, the substituted
benzene ring in 2-hydroxynaphthalene-1-carbaldehyde, 1-hy-
droxynaphthalene-2-carbaldehyde, and 10-hydroxyphenanthrene-
9-carbaldehyde is less aromatic than those in salicyl- and
3-hydroxynaphthalene-2-carbaldehydes.8,9
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 â-amino-R,â-
unsaturated 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
Chelation in the respective ortho-disubstituted benzenes has
an intermediate strength between 1,2- (or 2,1-) and 2,3-
disubstituted 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
10b,c
for the hydrogens on two carbons of the bond (3JH,H
)
for
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1129.
o-hydroxy derivatives of formyl-, acetyl-, and methoxycarbo-
nylbenzenes, naphthalenes, and phenanthrenes depend on mul-
tiplicity of the bond joining the ring carbon atoms holding the
substituents. On the other hand, not entirely concordant conclu-
sions on the bond fixation in naphthalene can be drawn from a
(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.
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J. Org. Chem, Vol. 72, No. 15, 2007 5599

Gawinecki et al.
â-Amino-R,â-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 hy-
drogen 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 5,6-
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, 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-hydroxy-
1-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
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 proton-
transfer process from oxygen to nitrogen atom in these
molecules 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 (silent
information regulator) which deacetylates R-tubulin and par-
ticipates 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-salicylide-
neaniline. 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.
(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, 11956-
11962.
(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, 2442-
2446. (b) Alarco´n, S. H.; Olivieri, A. C.; Labadie, G. R.; Cravero, R. M.;
Gonza´les-Sierra, M. Tert. 1995, 51, 4619-4626.
Results and Discussion
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Toscano, R. A.; Salcedo, R. J. Mol. Struct. 2001, 561, 197-207. (b)
Sitkowski, J.; Stefaniak, L.; Dziembowska, T.; Grech, E.; Jagodzin´ska, E.;
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J. C.; Farrant, R. D.; Carpenter, T. A. Magn. Reson. Chem. 1993, 31, 991-
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Mol. Struct. 2000, 524, 241-250. (f) Becker, R. S.; Richey, W. F. J. Am.
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embowska, T. Pol. J. Chem. 2000, 74, 1441-1446.
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Antonov, L.; Fabian, W. M. F.; Nedeltcheva, D.; Kamounah, F. S. J. Chem.
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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), N-
salicylidene-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.; Dziem-
bowska, 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.
(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,
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5600 J. Org. Chem., Vol. 72, No. 15, 2007

Benzo-Annulated N-Salicylideneanilines
SCHEME 2
SCHEME 3
SCHEME 4
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-aminoacetophe-
nones,30 or their benzo analogues. These compounds and their
tautomers are in fact dibenzo derivatives of cis,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 by
bifurcated hydrogen bonds (no respective (2Z)-3-[((1Z)-3-
oxoprop-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-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 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 stabi-
lized only by a single intramolecular hydrogen bond.
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 N-
salicylideneanthranilates, 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.
Multinuclear magnetic resonance spectroscopic techniques
have provided an excellent tool to investigate tautomeric
equilibria quantitatively.15a,b,37 It has been reported that proto-
nation-caused chemical shift changes of the ring nitrogen atom
in aza aromatic compounds are very large.38 Consequently, 15
N
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.; Sˆwistun, Z. J. Chem. Soc., B 1971, 818-821.
(b) Da¸browski, J.; Sˆwistun, Z. Tetrahedron 1973, 29, 2261-2267.
(34) Da¸browski, J.; Sˆwistun, Z.; Da¸browska, U.; Sˆwistun, 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.
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.
J. Org. Chem, Vol. 72, No. 15, 2007 5601

Gawinecki et al.
1
TABLE 1. Selected H, 13C, and 15N NMR Chemical Shifts (δ) and
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
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
1
chemical shifts and JNH (from -89.5 to -88.0 Hz) for these
no.
H7a
H8/H15a
C1
C6
C7
C16
N8b
compounds are typical for primary amides.40b
1
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)
13.08
13.27
15.76
(5.2)
15.48
12.58
12.74
14.86
(6.4)
159.22 118.04 162.42
161.14 117.23 162.63
170.95 108.37 155.24
-
-
-
-85.3
-85.0
-158.3
The H 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 DMSO-
d6 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
2
170.81 108.75 154.40
156.03 121.39 163.18
156.73 121.22 162.51
173.50 110.30 156.56
-
-
-
-
-150.0
-78.4
-78.5
-189.7
3
4
3
doublet (sometimes to a broadened singlet). The J(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(â-
acylvinyl)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
14.88
(8.2)
172.34 110.92 156.09
179.91 104.77 148.08
181.23 105.63 146.36
-
-
-
-173.7
5
6
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)
-234.2
(-83.5)
-235.4
(-85.1)
159.95 119.66 162.96 168.85 -85.3
160.75 119.04 165.28 168.29 -85.4
171.98 108.78 153.96 169.01
7
8
9
c
155.86 122.01 162.92 168.88 -79.0
176.31 110.79 153.43 168.93 -214.5
(-74.0)
10 9.03
(12.0)
12 9.42
(7.1)
180.30 105.94 145.65 169.04 -245.1
174.33 108.86 152.48 166.08 -184.9
9.06
(7.5)
15.22
(7.1)
176.40 109.27 149.63 166.43 -192.3
(-71.0)
1
the pure NH form JNH ) 89 Hz, the tautomeric equilibrium
13 9.03
8.70
14 8.79
(10.5)
8.13
12.40
12.53
14.63
(10.5)
14.75
(9.5)
14.86
(11.8)
14.87
(12.0)
15.00
(7.7)
152.41 118.77 165.89 165.89
d
constant in solution of 9 (1JNH ) 74 Hz) can be calculated from
156.67 119.23 162.81 166.49 -78.0
178.02 111.01 152.41 165.89 -233.3
(-78.0)
1
equation KT ) [89 - J(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.
179.08 111.69 150.12 166.49 -221.3
(-78.0)
The signal of N8 in the 15N NMR spectra of N-salicylide-
neanilines 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,
(9.9)
15 9.10
(11.8)
8.72
(11.9)
17 9.35
(7.7)
181.07 106.58 144.95 165.94 -250.5
(-92.0)
182.80 107.87 141.97 166.63 -250.5
(-93.0)
175.00 108.86 151.81 200.02 -191.5
9.07
(6.5)
19 8.72
(10.6)
8.59
15.05
(6.5)
14.59
(10.9)
14.77
(8.0)
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
(8.0)
(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. Spectrophoto-
metric 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.
20 9.06
(12.1)
8.72
14.86
(12.0)
15.02
(11.4)
180.86 106.71 144.73 200.13 -248.8
(-91.0)
182.59 108.11 141.79 199.62 -251.7
(-92.3)
(11.9)
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 Insufficient
solubility.
tautomeric mixtures when the proton exchange between indi-
vidual forms is fast on the NMR time-scale.37e Thus, in the case
when basic centers in the tautomers are the strongly electro-
negative 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 13
C
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

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
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).
no.
KT
NH form (%)a
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).
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
28
34
63.5
63
18
20
71
77.5
90.5 (87.0)
95 (88.6)
30
33
76.5
2
3
4
5
6
7
8
9
10
12
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)
13
14
15
17
19
20
164
3.13
3.14
6.40
6.67
The bond lengths of tautomeric forms were used to estimate
the geometry-based aromaticity index HOMA (Harmonic Oscil-
lator Model of Aromaticity)47 as defined in eq 1:
14.42
79.49
n
1
R (Ropt,i - Rj)2
(1)
a Data based on JNH values are given in parentheses.
1
HOMA ) 1 -
∑
i
n j)1
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 141.79-
162.63 ppm in DMSO-d6 and CDCl3, respectively (Table 1)
(the 13C chemical shift of C7 of N-(3-hydroxy-4-pyridinemeth-
ylidene)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 150.11-
161.14 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 tau-
tomers.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
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 automati-
cally 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.
(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.
(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.
(45) Alarco´n, S. H.; Olivieri, A. C.; Nordon, A.; Harris, R. H. J. Chem.
Soc., Perkin Trans. 2 1996, 2293-2296.
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
Lengths [pm] as Well as Bond and Interplanar Anglesa [deg] in
N-Salicylideneanilines 1-20 and Their Tautomers
Their Tautomersa
no./form C7-N8 C1-O15 C7N8C9 C7N8C9C14 C9C10C16O17
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
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
0.92
0.44
0.65 0.83
0.12 0.90
0.74
0.70
0.14
-
-
-
0.98 0.47
0.98 0.59
0.98 0.58
0.98 0.61
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
0.76 0.98 0.31
-
0.83
0.92
0.98 0.59
0.98 0.63
0.98 0.63
0.98 0.70
0.95 0.50 -0.12
0.91 0.47 -0.04
0.95 0.60 -0.11
0.94 0.54 -0.07
-8.64
3.55
-
-
-
-
-
-
-
0.35 0.88 0.90
-7.53
10.29
-8.40
-10.70
-7.45
-11.15
-7.18
-12.13
7.72
-0.15 0.91 0.94
0.91
0.22
0.63 0.83
0.01 0.91
0.74
0.68
0.02
CONH2
CONH2
CONH2
CONH2
CONH2
CONH2
CONH2
CONH2
-
-
-
-
-
-
-
-
-
-
0.75 0.96 0.33 -0.12
0.84
0.93
-
0.95 0.62 -0.11
0.94 0.54 -0.01
0.95 0.67 -0.10
0.94 0.60
0.95 0.48
0.94 0.50
0.94 0.60
0.93 0.51
-
-
-
-
-
-
-
5.71
0.33 0.88 0.90
-9.27
-16.73
-7.99
7.00
-2.47
6.99
CONH2 -0.19 0.92 0.94
0.00
0.05
0.11
0.04
0.13
0.05
0.05
0.03
0.14
0.04
0.14
CO2Me
CO2Me
CO2Me
0.92
0.28
0.64 0.83
-
-
-
-
-
-
-
-
CO2Me -0.02 0.91
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
0.75
0.37
0.69
0.01
-
-
-
-
0.76 0.95 0.32
0.49 0.95 0.47
-
a Data for extremely unstable forms (3NH, 8NH, and 18NH) are lacking
(see Discussion).
0.84
0.93
0.94 0.62
0.93 0.53
0.94 0.66
0.93 0.59
0.94 0.48 -0.05
0.92 0.48 0.02
0.93 0.58 -0.02
0.91 0.48 0.04
-
-
-
-
-
-
-
0.34 0.88 0.90
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 above-
mentioned 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).
CO2Me -0.26 0.94 0.92
COMe
COMe
COMe
COMe
COMe
COMe
COMe
COMe
COMe
0.92
0.24
0.64 0.83
-
-
-
-
-
-
-
-0.06 0.91
0.74
0.69
0.00
-
-
-
0.75 0.94 0.29 -0.02
0.93 0.59 -0.04
0.91 0.52 0.09
0.93 0.65 -0.03
0.91 0.58 0.09
0.83
0.93
-
-
-
-
0.34 0.88 0.90
-0.28 0.92 0.94
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 ortho-
quinoid 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
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
(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.
(49) Krygowski, T. M.; Zachara, J. E.; Moszyn´ski, R. J. Chem. Inf.
Model. 2005, 45, 1837-1841.
5604 J. Org. Chem., Vol. 72, No. 15, 2007

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 phenan-
threne 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).
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 pyrrole-
like 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 sub-
stituent 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-hydroxyphenan-
threne-9-carbaldehyde is the highest. In other cases the OH form
is more stable: this refers especially to the 3-hydroxynaphtha-
lene-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].
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-hydroxy-
naphthalene-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-2-
carbaldehydes 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-hydroxy-
naphthalene-1-carbaldehyde, 1-hydroxynaphthalene-2-carbal-
dehyde, 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 ben-
zylideneanilines 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-naphthylmethylide-
ne)aniline resemble 2-phenacylpyridine and 3-phenacylisoquino-
line (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-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 Although N-salicylidene derivatives of ortho-
C(dO)X substituted anilines are structurally similar to the
respective derivatives of dibenzo-cis,cis-bis(â-formylvinyl)-
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 â-amino-
R,â-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
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.
(in italics) for N-Salicylideneanilines 1-20 and Their Tautomers
E
abs(NH)a
E
abs(OH)a
E
rel(OH)b,c
no.
[Hartree]
[Hartree]
[kJ/mol]
1
-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
-
2
3
-
4
-783.699504
-783.714495
-936.967001
-936.982248
-798.780660
-798.806872
-952.050447
-952.076160
d
-15.24
-8.95
-5.08
-0.45
-40.64
-31.51
-17.77
-12.35
-
5
Experimental Section
6
Salicylaldehyde and 2-hydroxynaphthalene-1-carbaldehyde were
commercial 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,53,57 100-
102 °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-aminoacetophe-
none (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/
7
8
-
9
-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
-14.12
-8.74
-0.02
3.30
10
11
12
13
14
15
16
17
18
19
20
-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
-
-
-936.007471
-936.025283
-1089.276794
-1089.294838
-8.55
-2.90
6.04
(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, 789-
793.
9.90
a Absolute. b Relative. c Positive and negative value of Erel show that the
NH and OH form is more stable, respectively. d Data for extremely unstable
forms (3NH, 8NH and 18NH) are lacking (see Discussion).
(57) Przhiyalgovskaya, N. M.; Lavrishcheva, L. N.; Mondodoev, G. T.;
Belov, V. N. Zh. Obshch. Khim. 1961, 31, 2321-2325.
fact a benzo-annulated â-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
(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.
1
bonds, H, 13C, and 15N NMR spectra show that such species
are not present in solution of the parent N-salicylidene-ortho-
C(dO)X-anilines and their various benzo-annulated derivatives.
The stabilization of the NH tautomer in the dipolar, hydrogen-
bond 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 delo-
calization 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

Benzo-Annulated N-Salicylideneanilines
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) and 20 (229-231).
Satisfactory analytical data ((0.3% for C, H, and N) were obtained
for all new compounds.
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.
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)
Supporting Information Available: Molecular modeling co-
ordinates 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
J. Org. Chem, Vol. 72, No. 15, 2007 5607