Keto-enol tautomerism in asymmetric Schiff bases derived from p-phenylenediamine

Article abstract of DOI:10.1016/j.molstruc.2010.09.034

Reaction of dehydroacetic acid and p-phenylenediamine afforded a monosubstituted Schiff base, I, with the other amino group free. In further reactions with various salicylaldehyde derivatives, I served as a precursor for synthesis of asymmetric bis-Schiff bases. The synthesized compounds are thus comprised of two subunits, dehydroacetic (dha) and salicylidene (sal), which are bridged by the phenylene linker. All products were investigated by means of elemental analysis, FT-IR and NMR spectroscopy, thermal methods, powder X-ray diffraction and, when possible, by single crystal X-ray crystallography. Structural and spectroscopic studies revealed that in the bis-products, the dha subunit adopts the keto-amino tautomeric form, while the sal subunit adopts the enol-imino form. Tautomeric forms were not affected if a methoxo group was introduced on the salicylidene ring. Both tautomeric subunits are stabilized by strong resonance-assisted hydrogen bonds, RAHB. The two subunits of the prepared bis-Schiff bases predominantly retain in solution the same tautomeric forms as found in the solid state.

Full text of DOI:10.1016/j.molstruc.2010.09.034

Journal of Molecular Structure 984 (2010) 232–239
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Keto–enol tautomerism in asymmetric Schiff bases derived from
p-phenylenediamine
⇑
ˇ
´
ˇ ´
´
´
Krunoslav Uzarevic , Mirta Rubcic, Vladimir Stilinovic, Branko Kaitner, Marina Cindric
Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia
a r t i c l e i n f o
a b s t r a c t
Article history:
Reaction of dehydroacetic acid and p-phenylenediamine afforded a monosubstituted Schiff base, I, with
the other amino group free. In further reactions with various salicylaldehyde derivatives, I served as a
precursor for synthesis of asymmetric bis-Schiff bases. The synthesized compounds are thus comprised
of two subunits, dehydroacetic (dha) and salicylidene (sal), which are bridged by the phenylene linker.
All products were investigated by means of elemental analysis, FT-IR and NMR spectroscopy, thermal
methods, powder X-ray diffraction and, when possible, by single crystal X-ray crystallography. Structural
and spectroscopic studies revealed that in the bis-products, the dha subunit adopts the keto–amino tau-
tomeric form, while the sal subunit adopts the enol–imino form. Tautomeric forms were not affected if a
methoxo group was introduced on the salicylidene ring. Both tautomeric subunits are stabilized by strong
resonance-assisted hydrogen bonds, RAHB. The two subunits of the prepared bis-Schiff bases predomi-
nantly retain in solution the same tautomeric forms as found in the solid state.
Received 19 July 2010
Received in revised form 21 September
2010
Accepted 23 September 2010
Available online 29 September 2010
Keywords:
Dehydroacetic acid
Keto–enol tautomerism
Asymmetric Schiff bases
Resonance-assisted hydrogen bond
Crystal engineering
Ó 2010 Elsevier B.V. All rights reserved.
1. Introduction
Symmetric bis-Schiff bases of salicylaldehyde derivatives and
p-phenylenediamine are well described in the literature. CSD search
Schiff bases derived from aromatic o-hydroxyaldehydes are
well known models for the study of keto–enol tautomerism as well
as proton transfer mechanisms [1–4]. Proton transfer equilibrium
is considered to have a major impact on the physicochemical prop-
erties of these compounds (e.g. thermochromism and photochro-
mism) [5–7]. Molecular structures of such molecules are
characterized by strong intramolecular NAHÁ Á ÁO or OAHÁ Á ÁN reso-
nance-assisted hydrogen bonds, RAHB [8,9]. Consequently, part of
the molecule that is involved in RAHB assumes an almost planar
conformation. Since the proton is positioned between oxygen
and nitrogen atoms involved in RAHB, the prototropy in these sys-
tems is considered to be facilitated. On the molecular level, posi-
tion of the proton designates the nature of the donor
functionality, which consequently determines the reactivity of
the compound and has an influence on intermolecular forces stabi-
lizing the crystal structure. While contributing factors, such as sub-
stituents, solvent and molecular conformation, on the occurrence
of either keto–amino or enol–imino tautomer, were widely studied
by various techniques in solution and in the solid state [10–14], the
available information for Schiff bases constituted of both a keto–
amino and an enol–imino tautomeric moieties is still rather scarce
[15–19].
[20] revealed that these compounds crystallise predominately in the
enol–imino tautomeric form. However, the tautomeric form can be
altered by introduction of electron withdrawing/donating substitu-
ent(s) on the salicylidene ring [21]. Dehydroacetic acid, dha (3-acet-
yl-4-hydroxy-6-methyl-2H-pyran-2-one), a heterocyclic compound
often used in organic synthesis and pharmaceutical industry [22], is
known to adopt almost exclusively keto–amino form in its Schiff
bases [23]. Intramolecular RAHB in these systems, based on a six
membered ring, is very strong and has great influence on reactivity
of themolecule[24–26]. Althoughspectroscopic investigations indi-
cate that dha-based Schiff bases containing both the keto–amino
and the enol–imino subunits exist in the solution, no structural
evidence of such structures was found so far [27].
Herein we report a simple two-step synthetic approach for the
preparation of asymmetric bis-Schiff bases derived from p-pheny-
lenediamine, dha and assorted salicylidene-based aldehydes: salicyl-
aldehyde, 3-methoxysalicylaldehyde, 4-methoxysalicylaldehyde and
5-methoxysalicylaldehyde. The first step is the synthesis of the dha-
monosubstituted amine, I, which acts as a precursor for the syntheses
of asymmetric Schiff bases in reactions with the corresponding alde-
hydes. The synthesized molecules are constituted from two subunits
on the opposite sides of the diamine, each adopting a different tauto-
meric form. In all cases, the dha subunit assumes the keto–aminotau-
tomeric form, whereas the sal subunit is found in the enol–imino
form. Spectroscopic and thermal properties were investigated for
the monosubstituted amine and for all bis-Schiff bases. Additionally,
⇑
Corresponding author. Tel.: +385 1 4606350; fax: +385 1 4606341.
ˇ
´
E-mail address: kruno@chem.pmf.hr (K. Uzarevic).
0022-2860/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2010.09.034

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K. Uzarevic et al. / Journal of Molecular Structure 984 (2010) 232–239
solid-state structures of the monosubstituted amine I, and its salicy-
2.2. Methods
lidene and 3-methoxysalicylidene derivatives were determined via
single crystal X-ray diffraction.
Elemental analyses were performed by Central Analytical Ser-
-
´
vice, Ruder Boškovic Institute, Zagreb. IR spectra were recorded
on PerkinElmer Spectrum RXI FT-IR spectrometer (KBr pellet tech-
nique, 4000–400 cmÀ1 range, 2 cmÀ1 step). Thermogravimetric
analyses were performed on a Mettler-Toledo TGA/SDTA851e ther-
mobalance using aluminium crucibles under nitrogen stream with
the heating rate of 5 °C minÀ1. The results were processed with the
Mettler STARe 9.01 software. DSC measurements were performed
in the temperature range of 25–400 °C, under the nitrogen stream,
on the Mettler-Toledo DSC823e calorimeter with STARe SW 9.01
(5 °C minÀ1). The one- and two-dimensional 1H and 13C NMR spec-
tra were recorded in acetonitrile-d3 (for I) and chloroform-d1 (for
II–V) with Bruker AV-600 spectrometer, 1H operating at
600.13 MHz and 13C at 150.90 MHz. The 1HA1H COSY spectra were
obtained in the magnitude mode with 2048 points in the F2 dimen-
sion and 512 increments in the F1 dimension. The 1HA13C HMQC
spectra were measured with one-bond C,H coupling value set to
145 Hz, using 2048 points in the F2 dimension and 256 increments
in the F1 dimension. The 1HA13C HMBC spectra were measured
with C,H coupling value set to 145 and 8 Hz using 2048 points in
the F2 dimension and 256 increments in the F1 dimension. All
two-dimensional experiments were performed by standard pulse
sequences using Bruker XWIN-NMR software Version 3.5. Waltz
16 modulation was used for proton decoupling. X-ray powder dif-
fraction patterns used for qualitative analysis of the samples were
2. Experimental section
2.1. Materials
Dehydroacetic acid, salicylaldehyde, 3-methoxysalicylaldehyde,
4-methoxysalicylaldehyde and 5-methoxysalicylaldehyde were
obtained from Sigma–Aldrich and used without further purifica-
tion. Para-phenylenediamine was obtained from Sigma–Aldrich
and recrystallised from hot ethanol before use. Solvents used in
syntheses (p.a. grade) were purchased from Kemika, Zagreb, and
distilled before use.
2.1.1. Synthesis of monosubstituted Schiff base (I)
1,4-Phenylenediamine was added in slight excess (0.81 g,
7.5 mmol) to a hot methanolic solution (10 mL) containing dehyd-
roacetic acid (0.85 g, 5.0 mmol). The reaction mixture was refluxed
and stirred for 1 h. After standing overnight, dark yellow prismatic
crystals of I were filtered off, washed with small amounts of cold
ethanol and dried under vacuum (1.10 g, 85%;).
Anal. Calcd. for C14H14N2O3 (I): C, 65.11; H, 5.46; N, 10.85%.
Found: C, 65.01; H, 5.32; N, 11.21%. IR (KBr)
3354(m), 1698(s), 1658(s), 1614(s), 1560(s).
m
(cmÀ1): 3466(m),
collected on a Philips PW 3710 diffractometer, CuKa radiation, flat
2.1.2. Syntheses of bis-Schiff bases (II–V)
plate sample on a zero background in Bragg–Brentano geometry,
tension 40 kV, current 40 mA. The patterns were collected in the
angle region between 4° and 40° (2h) with the step size of 0.02°
and 1.0 s counting per step.
The crystal and molecular structures of I, II, III and IIIÁMeCN were
determined by single crystal X-ray diffraction. The diffraction data
for I were collected at 113(2) K and for other crystals at room tem-
perature. Diffraction measurements were made on an Oxford Dif-
fraction Xcalibur Kappa CCD X-ray diffractometer with graphite-
I (0.52 g, 2 mmol) was dissolved in 5 mL of hot methanol, and
2 mmol of corresponding aldehyde [salicylaldehyde (II); 3-meth-
oxysalicylaldehyde (III); 4-methoxysalicylaldehyde (IV) and 5-
methoxysalicylaldehyde (V)] was added to the prepared solution.
Reaction mixture was stirred and refluxed for 2 h and left to stand
overnight. Pale yellow crystals of II (0.47 g, 65%) and III (0.58 g,
74%) were of satisfying quality for X-ray diffraction experiments.
Crystals of IV (0.25 g, 32%) and V (0.64 g, 82%) were inadequate
for structural investigations.
Anal. Calcd. for C21H18N2O4 (II): C, 69.60; H, 5.01; N, 7.73%.
Found: C, 69.24; H, 4.89; N, 7.52%. IR (KBr)
1699(s), 1654(s), 1616(m), 1599(m).
Anal. Calcd. for C22H20N2O5 (III): C, 67.34; H, 5.14; N, 7.14%.
Found: C, 67.02; H, 5.25; N, 7.20%. IR (KBr)
2592(m), 1695(s), 1663(m), 1612(s), 1559(s).
monochromated Mo K
were collected using the
a
(k = 0.71073 Å) radiation [28]. The data sets
scan mode over the 2h range up to 54°.
x
m
(cmÀ1): 3432(m),
The structures were solved by the direct methods and refined using
SHELXS and SHELXL programs [29]. The structural refinement was
performed on F2 using all data. The hydrogen atoms not participat-
ing in hydrogen bonding were placed in calculated positions and
treated as riding on their parent atoms [CAH = 0.93 Å and Ui-
so(H) = 1.2 Ueq(C); CAH = 0.97 Å and Uiso(H) = 1.2 Ueq(C)] and the
hydrogen atoms participating in the hydrogen bonding were located
from the electron difference map. All calculations were performed
and the drawings were prepared using WINGX crystallographic
suite of programs [30]. The crystal data are listed in Table 1. Further
details are available from the Cambridge Crystallographic Centre
with quotation numbers 784134–784137.
m
(cmÀ1): 3452(m),
Anal. Calcd. for C22H20N2O5 (IV): C, 67.34; H, 5.14; N, 7.14%.
Found: C, 67.12; H, 5.10; N, 7.12%. IR (KBr)
1695(s), 1654(m), 1618(s), 1576(m), 1559(m).
Anal. Calcd. for C22H20N2O5 (V): C, 67.34; H, 5.14; N, 7.14%.
Found: C, 67.32; H, 5.08; N, 7.05%. IR (KBr)
2919(w), 1694(s), 1618(m), 1575(s), 1555(m).
m
(cmÀ1): 3446(m),
m
(cmÀ1): 3447(m),
2.1.3. Polymorph screening experiments
Influence of the solvent on the occurrence of new polymorphic or
tautomeric speciesof the prepared bis-Schiff bases was investigated.
Compound I was readily soluble in acetonitrile and methanol, and
almost insoluble in the other non-protic solvents. On the other hand,
all prepared bis-Schiff bases were poorly soluble in protic solvents
(alcohols: methanol, ethanol, 1-propanol, 2-propanol, 1-butanol)
and displayed better solubility in dichloromethane and chloroform.
All collected samples were identical to their starting compounds
(confirmed by powder X-ray diffraction, PXRD). Only in the case of
III, crystallisation from acetonitrile yielded air-unstable crystals of
the acetonitrile solvate, IIIÁMeCN, suitable for structural investiga-
tions. Due to the acetonitrile egress from the structure, elemental
analyses for the desolvated IIIÁMeCN were in good agreement with
compound III.
3. Results and discussion
During our recent studies on intra- and intermolecular hydrogen
bonding patterns in Schiff bases derived from dha and o-phenylene-
diamine and their complexation abilities, two different products
have been obtained, a monosubstituted [22] and a bis-substituted
Schiff base [31]. It has been also established that the reaction can
be selectively directed towards the formation of exclusively one of
the two products by adjusting the reaction time and the tempera-
ture. Thus, the bis-Schiff base can only be obtained on a prolonged
reaction time and higher temperature of the reaction mixture. In or-
der to examine if the formation of the bis product was hindered by
sterical requirements of the two bulky substituents of dha, o-phen-
ylenediamine was replaced with its para isomer. Such reaction

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K. Uzarevic et al. / Journal of Molecular Structure 984 (2010) 232–239
234
Table 1
Crystal data and summary of experimental details for compounds I, II, III and IIIÁMeCN.
I
II
III
IIIÁMeCN
Molecular formula
Mr
Crystal system
Space group
C
14H14N2O3
C21H18N2O4
362.37
Triclinic
C22H20N2O5
392.37
Triclinic
C22H20N2O5ÁC2H3N
258.27
Monoclinic
C2/c
433.45
Monoclinic
P21/c
P1
P1
Crystal data
a (Å)
b (Å)
19.507(2)
9.705(1)
13.136(1)
90
101.54(1)
90
2436.7(4)
8
6.6680(3)
11.2487(8)
12.2850(7)
106.736(6)
94.698(4)
90.269(5)
879.07(9)
2
7.7440(5)
10.4490(6)
12.2822(9)
84.470(5)
75.329(6)
85.051(5)
955.0(1)
2
9.688(1)
31.927(2)
7.6838(8)
90
110.49 (1)
90
2226.1(4)
4
c (Å)
a
(°)
b (°)
c
(°)
V (Å3)
Z
qcalc (g cmÀ3
)
1.408
1.369
1.365
1.293
k (MoK ) (Å), graphite monochromator
0.71073
113(2)
0.71073
295(2)
0.71073
295(2)
0.71073
295(2)
a
T (K)
Crystal dimension (mm3)
0.22 Â 0.15 Â 0.11
0.74 Â 0.28 Â 0.08
0.13 Â 0.07 Â 0.06
0.42 Â 0.08 Â 0.07
l
(mmÀ1
)
0.101
0.096
0.098
0.092
F(0 0 0)
1088
380
412
912
h k l range
Number of measured reflections
Number of independent reflections
À24, 24; À11, 11; À16, 16
À7, 7; À13, 9; À14, 14
À9, 9; À11, 12; À14, 14
À12, 12; À40, 38; À9, 9
10,376
2386
6649
8051
15,284
4759
2970
3349
Number of reflections with I > 2
r(I)
1254
1794
1489
1985
Number of parameters
186
251
273
326
D
qmax
,
D
qmin (e ÅÀ3
)
0.247, À0.228
0.0540
0.1414
0.914
0.138, À0.143
0.135, À0.118
0.148, À0.173
0.0639
0.1371
0.914
R[F2 > 4
r
(F2)]
0.0661
0.0381
wR(F2)
0.1652
1.043
0.0832
0.791
Goodness-of-fit, S
yielded crystals of monosubstituted product I in high yield. This re-
sult strongly suggests that the sterical effects cannot account for the
somewhat more demanding synthesis of the bis-dha derivative of o-
phenylenediamine. On the other hand, I was recognized as poten-
tially good precursorfor the synthesisof asymmetric bis-Schiff bases
with adjustable functionalities on the opposite sides of the bridging
diamine. Reactions of I with salicylaldehyde, 3-methoxysalicylalde-
hyde, 4-methoxysalicylaldehyde and 5-methoxysalicylaldehyde in
methanol yielded pure phases of heterosubstituted bis-Schiff bases
possessing at the same time the keto–amino (dha subunit) and the
enol–imino (sal subunit) tautomeric fragments in the same mole-
cule (Scheme 1).
of C@O, C@C and C@N bonds included in RAHB, as was further con-
firmed by structural studies. The main difference in the spectra of
the prepared bis-Schiff bases is the disappearance of the two sharp
bands at ꢀ3400 cmÀ1, and the appearance of a broad medium
strong band at ꢀ3440 cmÀ1 (Fig. 1). This broadening can be as-
cribed to the existence of two RAHB systems, NAHÁ Á ÁO and
OAHÁ Á ÁN of the dha and of the sal subunits, respectively.
3.2. Thermal studies
Thermogravimetric measurement of IIIÁMeCN was primarily
conducted to establish the content of acetonitrile in the compound.
The first step in the thermogram is observed in the temperature
3.1. IR spectroscopy
IR spectrum of I exhibits two sharp bands at 3466 cmÀ1 and
3354 cmÀ1 assigned to NH2 stretching vibrations of the free amino
group. Since the bands are sharp, it can be assumed that they do
not participate in strong intermolecular hydrogen bonding. Strong
band at 1698 cmÀ1 corresponds to C@O vibration of the dha keto
group not involved in RAHB. Position of bands at 1658 cmÀ1
,
1614 cmÀ1 and 1560 cmÀ1 is consistent with the resonant nature
Fig. 1. IR spectra for I (red, top) and II (blue, bottom) in the range of 4000–
1500 cmÀ1. Bands important for discussion are denoted with an asterisk (Ã). (For
interpretation of the references to colour in this figure legend, the reader is referred
to the web version of this article.).
Scheme 1. Representation of bis-Schiff bases with carbon atom numbering.

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K. Uzarevic et al. / Journal of Molecular Structure 984 (2010) 232–239
Table 2
Hydrogen bonds in the crystal structures of mono and bis-substituted Schiff bases.
Hydrogen
bond
d(DAH)
(Å)
d(HÁ Á ÁA) d(DÁ Á ÁA)
Angle
Symmetry
(Å)
(Å)
(DAHÁ Á ÁA) operator
(°)
I
N1AH1Á Á ÁO3
0.99(3)
N2AH2AÁ Á ÁO3 0.93(3)
1.68(3)
2.23(3)
2.550(3)
3.127(3)
145(2)
165(2)
1/2 À x, À1/
2 + y, 1/2 À z
N2AH2BÁ Á ÁO1 0.95(4)
2.35(3)
3.180(3)
145(2)
À1/2 + x, 1/
2 + y, z
Fig. 2. ORTEP presentation of I; ellipsoids are drawn at the 50% probability level.
Hydrogen atoms are presented as spheres of arbitrary small radii; colour code:
carbon – grey; oxygen – red; nitrogen – blue; hydrogen – white. (For interpretation
of the references to colour in this figure legend, the reader is referred to the web
version of this article.).
II
O4AH2Á Á ÁN2
N1AH1Á Á ÁO3
N1AH1Á Á ÁO3
0.82
0.83(4)
0.83(4)
1.87
1.84(3)
2.61(5)
2.598(3)
2.561(3)
3.164(4) Å 126(4)
147
145(4)
1 À x, 1 À y,
1 À z
III
O4AH2Á Á ÁN2
0.96(2)
1.72(2)
2.587(2)
149(2)
147.7(17)
range 30.0–88.9 °C and is attributed to the loss of acetonitrile. The
mass loss in this step amounts to 9.55% and fits well with the cal-
culated value for the 1:1 solvate (III:acetonitrile = 1:1 ratio; 9.49%).
DSC curves for compounds II, IV, V and I are very similar. The first
thermal event is observed in all cases around 200 °C, and is assigned
to melting(Fig. S5, Supplementarydata). Additionally, all DSC curves
are characterized by a strong exotherm observed in the range be-
tween 240 °C and 260 °C. This exotherm is associated with the deg-
radation of the melt. Among the samples, I has the highest melting
point (210.8 °C, onset), while the melting points of bis-Schiff bases
indicate weaker intermolecular forces stabilizing their crystal struc-
tures (II – 191.2 °C; IV – 201.5 °C; V – 199.8 °C). The DSC curve of III
displays a couple of broad endotherms before melting (188.1 °C,
onset).
N1AH1Á Á ÁO3
0.927(17) 1.700(19) 2.532(2)
IIIÁMeCN
O4AH2Á Á ÁN2
N1AH1Á Á ÁO3
0.82
0.90(3)
1.89
1.73(3)
2.608(3)
2.546(3)
146
149(2)
3.3. Crystal structures
Crystal and molecular structures of compounds I, II and III, as
well as of the acetonitrile solvate of III, IIIÁMeCN, were determined
by single crystal X-ray diffraction.
Compound I crystallises in the monoclinic C2/c space group
with 8 molecules per unit cell. The molecules consist of two planar
cyclic fragments, i.e. the dha subunit and the phenylene ring
(Fig. 2). The dihedral angle between the two rings is 40.0°. The
dha subunit is in the keto–amino tautomeric form. The location
of the hydrogen atom at the nitrogen atom is determined both
from electron density map and the bond lengths (d(N1AC7) of
1.315(4) Å and d(C6AO3) of 1.270(3) Å). The secondary amino
and the keto groups are connected via an intramolecular hydrogen
bond (N1AH1Á Á ÁO3) of 2.550(3) Å (Table 2). The primary amino
group forms two hydrogen bonds with carbonyl oxygen atoms of
two neighbouring molecules (N2AH2AÁ Á ÁO3 of 3.127(3) Å, [1/
2 À x, À1/2 + y, 1/2 À z] and N2AH2BÁ Á ÁO1 of 3.180(3) Å, [À1/
2 + x, 1/2 + y, z]). These hydrogen bonds interconnect the molecules
into sheets parallel to the ab plane. The higher melting point of I in
comparison to other compounds can probably be attributed to this
hydrogen-bond network.
ꢀ
Compound II crystallises in the triclinic P1 space group with
two molecules per unit cell. The molecule consists of three cyclic
fragments, namely the dha and sal subunits and the phenylene lin-
ker. The dha and sal subunits are almost parallel, with the dihedral
angle of 6.2°, and the phenylene ring plane is at angles of 37.9° and
43.9° with dha and sal subunits respectively. As in compound I, the
dha subunit is in keto–amino tautomeric form. The equivalent
bond lengths are similar to those in I (d(N1AC7) of 1.318(4) Å
and d(O3AC6) of 1.254(3) Å). An intramolecular hydrogen bond
(N1AH1Á Á ÁO3) of 2.561(3) Å, analogous to that found in I, is present
in the dha subunit. The sal subunit is in the enol–imino tautomeric
form, i.e. the hydrogen atom is placed on the salicylidene oxygen
with the N2AC15 bond length of 1.271(4) Å and O4AC17 bond
Fig. 3. Electron difference maps for (a) the dha and (b) sal subunits of II showing
the location of the RAHB hydrogen atoms.

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K. Uzarevic et al. / Journal of Molecular Structure 984 (2010) 232–239
236
Fig. 4. Hydrogen-bonded dimers in the crystal structure of II. Hydrogen bonds are presented as dotted yellow lines. Colour code as in Fig. 2. (For interpretation of the
references to colour in this figure legend, the reader is referred to the web version of this article.).
Fig. 5. ORTEP presentation of bis-Schiff base of (a) II; (b) III; and (c) IIIÁMeCN (acetonitrile is omitted for clarity). Ellipsoids are drawn at the 50% probability level. Colour code
as in Fig. 2. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.).
length of 1.341(3) Å (Figs. 3 and 4). The phenol hydroxyl group par-
ticipates in an intramolecular hydrogen bond (O4AH2Á Á ÁN2) of
2.598(3) Å. The molecules are connected via longer hydrogen
bonds N1AH1Á Á ÁO3 of 3.164(4) Å [1 À x, 1 À y, 1 À z] into dimers
about inversion centres. These dimers are further connected by
lene ring (36.1° and 38.2°, respectively). The dha subunit remains in
the keto–amino (d(N1AC7) of 1.331(3) Å and d(O3AC6) of
1.258(3) Å), and the sal subunit in the enol–imino tautomeric form
(d(N2AC15) of 1.288(3) Å and d(C17AO4) of 1.359(3) Å). The intra-
molecular hydrogen bonding in III is equivalent to that in II with a
N1AH1Á Á ÁO3 of 2.532(2) Å in the dha subunit, and an O4AH2Á Á ÁN2
hydrogen bond of 2.587(2) Å in the sal subunit. Main difference in
the conformations of II and III is in the orientation of the dha and
sal subunits relatively to the bridging phenylene ring (clearly visible
from the orientation of the O3 and O4 atoms: II-anti and III-syn). The
molecules are connected by CAHÁ Á ÁO hydrogen bonds into chains
along the [0 À1 1] direction.
CAHÁ Á ÁO and CAHÁ Á Á
p interactions into chains along the a axis
(Table S1, Supplementary data).
ꢀ
Compound III crystallises in the triclinic P1 space group with two
molecules per unit cell. The addition of the methoxy substituent in
the position 3 of the sal subunit does not significantly alter the
molecular geometry (Fig. 5); the dha and sal subunits remain almost
parallel (dihedral angle of 3.9°) and at an angle to the central pheny-

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´
237
K. Uzarevic et al. / Journal of Molecular Structure 984 (2010) 232–239
1.286(4) Å and d(C17AO4) of 1.348(4) Å sal subunit) or in intramo-
lecular hydrogen bonding to that present in pure III (N1AH1Á Á ÁO3
of 2.546(3) Å in the dha subunit, and O4AH2Á Á ÁN2 hydrogen bond
of 2.608(3) Å in the sal subunit). The molecules are connected by
CAHÁ Á ÁO hydrogen bonds into pleated sheets parallel to the bc
plane. These sheets are further packed along the a direction leaving
channels along the c direction which are occupied by disordered
acetonitrile molecules (Fig. 7). Acetonitrile molecules are con-
nected to the molecules of III by weak hydrogen bonds.
3.4. Solution 1H and 13C NMR spectroscopy
Herein presented Schiff bases have been additionally investi-
gated by means of 1H and 13C NMR spectroscopy in order to estab-
lish the dominant tautomeric forms of the two subunits (sal and
dha) in solution. The solution structures as well as the 1H and
13C NMR assignments were confirmed by two-dimensional (COSY,
HMBC, HMQC) NMR spectroscopy. The NMR spectra for com-
pounds II–V were recorded in chloroform (CDCl3), whereas for
compound I the spectra were obtained in acetonitrile (CD3CN),
due to its poor solubility in chloroform. The relevant NMR data
are given in Table 3.
For all investigated Schiff bases, I–V, both 1H and 13C NMR spec-
tra display set of signals characteristic of the dehydroacetic moiety
[25,32]. It is evident from Table 3 that the chemical shifts for these
signals do not vary significantly, thus indicating that in all exam-
ined compounds the dha subunit retains the same tautomeric
form. The aromatic protons and carbon atoms belonging to the p-
phenylenediamine moiety, except for the compound I, are also
characterized by similar chemical shifts. The observed difference
for the compound I is addressed to the presence of the free NH2
moiety. Subsequently it influences chemical shifts, particularly
those of atoms of the p-phenylenediamine unit found in the ortho
and meta position with respect to the amino group (Table 3). How-
ever, the biggest difference in chemical shifts and multiplicities is
observed for the signals of atoms constituting sal moiety, which
is caused by the different position of the methoxo group on the sal-
icylidene ring.
Fig. 6. Structure overlay over dha subunits of (a) I and IIIÁMeCN; (b) III and
IIIÁMeCN and (c) all three structurally characterized bis-Schiff bases. Colour code:
orange – I, black – II, grey – III, red – IIIÁMeCN. (For interpretation of the references
to colour in this figure legend, the reader is referred to the web version of this
article.).
Crystallisation of III from acetonitrile afforded
a solvate,
IIIÁMeCN. The stoichiometry of the solvate is 1:1, as is shown both
by the structure determination and by the thermal analysis. The
differences in the molecular conformation to the molecule of III
are mostly related to the angles between the dha and sal subunits
and the plane of the phenylene linker (Fig. 6). There are no signif-
icant differences in the bond distances (d(N1AC7) of 1.333(4) Å
and d(O3AC6) of 1.266(3) Å in the dha subunit, d(N2AC15) of
The chemical shift of the carbon atom bearing an enol/keto
functionality is known to be a sensitive diagnostic tool for estab-
Fig. 7. The packing diagram of IIIÁMeCN viewed along the c axis. Acetonitrile molecules occupying channels along the c axis are shown as spacefill models.

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´
K. Uzarevic et al. / Journal of Molecular Structure 984 (2010) 232–239
238
Table 3
Assigned 1H and 13C chemical shifts (ppm, relative to TMS).
Compound
I
II
III
IV
V
Carbon
dC
dH
dC
dH
dC
dH
dC
dH
dC
dH
1
97.98
–
97.58
–
97.51
–
97.54
–
97.58
–
2
3
4
5
6
7
8
9
164.74
164.85
20.14
107.84
185.83
177.00
20.61
135.12
127.46
115.69
149.26
–
–
–
–
–
–
–
–
–
–
163.36
163.58
19.93
107.14
184.98
175.30
20.34
134.88
126.61
122.32
148.27
163.64
118.99
161.19
117.39
133.71
119.29
132.54
–
–
–
163.27
163.51
19.87
107.07
184.90
175.23
20.67
134.90
126.56
122.29
147.88
163.59
118.89
151.36
148.47
115.27
118.77
123.94
56.19
–
–
163.40
163.52
19.93
107.16
184.96
175.28
20.33
134.35
126.50
122.16
148.36
162.47
112.97
163.80
101.11
164.42
107.50
133.82
55.51
–
–
163.34
163.58
19.93
107.13
184.96
175.28
20.33
134.90
126.60
122.32
148.26
163.36
118.57
155.48
118.22
121.11
152.43
115.51
55.96
–
–
2.11 (s, 3H)
5.71 (s, 1H)
–
–
2.49 (s, 3H)
–
6.96 (d, 2H)
6.70 (d, 2H)
–
–
–
–
–
–
–
–
–
2.15 (s, 3H)
5.77 (s, 1H)
–
–
2.65 (s, 3H)
–
7.24 (d, 2H)
7.35 (d, 2H)
–
8.63 (s, 1H)
–
2.17 (s, 3H)
5.77 (s, 1H)
–
–
2.64 (s, 3H)
–
7.24 (d, 2H)
7.36 (d, 2H)
–
8.65 (s, 1H)
–
2.18 (s, 3H)
5.78 (s, 1H)
–
–
2.64 (s, 3H)
–
7.22 (d, 2H)
7.33 (d, 2H)
–
8.56 (s, 1H)
–
2.17 (s, 3H)
5.77 (s, 1H)
–
–
2.64 (s, 3H)
–
7.23 (d, 2H)
7.35 (d, 2H)
–
8.60 (s, 1H)
–
10, 14
11,13
12
15
16
17
18
19
20
21
22
–
–
–
–
–
7.04 (d, 1H)
7.40a (m)
6.96 (t, 1H)
7.40a (m)
–
6.52a (m)
–
6.97 (d, 1H)
7.03 (dd, 1H)
–
6.91 (d, 1H)
3.81 (s, 3H)
7.02 (d, 1H)
6.91 (t, 1H)
7.04 (d, 1H)
3.94 (s, 3H)
6.52a (m)
7.30 (d, 1H)
3.86 (s, 3H)
NH (dha)
NH2
OH (sal)
–
–
–
15.53 (s, 1H)
4.37 (s, 2H)
–
–
–
–
15.88 (s, 1H)
–
12.88 (s, 1H)
–
–
–
15.89 (s, 1H)
–
13.28 (s, 1H)
–
–
–
15.86 (s, 1H)
–
13.39 (s, 1H)
–
–
–
15.89 (s, 1H)
–
12.45 (s, 1H)
a
Multiplicities, when integrated, correspond to two hydrogen atoms.
lishing tautomeric equilibrium [33]. When the molecule is present
in the enol–imino form the chemical shift of such carbon atom is
usually found at ꢀ160 ppm. On the contrary, when the keto–amino
form is favoured, the C atom of the C@O group is found at
ꢀ180 ppm, due to a deshielding effect. Another valuable parameter
in distinguishing between tautomeric forms is considered to be the
signal of the hydrogen atom of the azomethine CH group (H15).
When the molecule is present in the enol–imino form, the corre-
sponding signal is a singlet. When the hydrogen atom is bound
to the adjacent nitrogen atom, i.e. in the keto–amino form, this sig-
nal is, due to the HANH coupling, split into a doublet [34].
13C NMR spectra of all investigated compounds are character-
ized by a signal at ꢀ185 ppm, assigned to the C6 atom of the dha
subunit (Table 3). Based on previous considerations, this clearly
indicates the existence of the dha moiety in the keto–amino form
in solution. This conclusion is further supported by the literature
data on tautomerism of dehydroacetic acid and its derivatives
[25,32,35]. On the other hand, for compounds II–V, a signal ad-
dressed to the C17 carbon atom of the sal subunit was found in
the range 151–164 ppm. Furthermore, the signal of the azomethine
CH group appears in 1H NMR spectra of II–V as a singlet. It can thus
be concluded that the sal subunit in all of the synthesized bis-
Schiff bases mainly adopts the enol–imino form. Singlets observed
in 1H NMR spectra at ꢀ15 ppm (I–V) and at ꢀ13 ppm (II–V) were
assigned to the NH and OH protons, respectively, and are consis-
tent with the resonant nature of the intramolecular hydrogen
bond.
by strong intramolecular NAHÁ Á ÁO or OAHÁ Á ÁN RAHB, which are
perceived in the solid state as well as in the solution. Asymmetric
ligands possessing both keto–amino and enol–imino subunits
within the same molecule represent interesting systems with po-
tential application as selective reagents in complexation processes
due to the divergence in the pK values of the amino and enol donor
functionalities. Also, a possibility to control the spatial arrange-
ment of strong hydrogen-bond donors and acceptors on the oppo-
site sides of a symmetric linker could allow the construction of
materials with tuneable properties, which is one of the goals of
crystal engineering. Our further investigations will be concentrated
in that direction.
Acknowledgments
This work was done with the financial support of the Ministry
of Science, Education and Sports of the Republic of Croatia (Grant
Nos. 119-1191342-1082 and 119-1193079-3069). We are grateful
to Dr. Ivan Halasz for helpful discussions.
Appendix A. Supplementary material
Thermogravimetric analysis of IIIÁMeCN; DSC curves for all
products; packing diagrams for crystal structures of all structurally
characterized products; Intermolecular CAHÁ Á ÁO interactions for I,
II, III and IIIÁMeCN forms. Supplementary data associated with this
article can be found, in the online version, at doi:10.1016/
j.molstruc.2010.09.034.
4. Conclusion
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