Intramolecular hydrogen bonding and tautomerism in schiff bases: Synthesis, spectroscopic and theoretical studies of n-(2,2'-methylenebis(4-methoxyphenyl) salicylidene and n-(2,2'-methylenebis(4-methoxyphenyl)-2-oxonaphthalidene- methylamine

Article abstract of DOI:10.14233/ajchem.2014.16725

The new Schiff bases (4 and 5) were synthesized respectively from the reaction of 2,2'-methylenebis(4-aminomethoxybenzene) (3) with salicylaldehyde and 2-hydroxy-1-naphthaldehyde. The products have been characterized by elemental analysis, FTIR, UV-visibl

Full text of DOI:10.14233/ajchem.2014.16725

Asian Journal of Chemistry; Vol. 26, No. 9 (2014), 2759-2767
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.16725
Intramolecular Hydrogen Bonding and Tautomerism in Schiff Bases: Synthesis, Spectroscopic
and Theoretical Studies of N-(2,2'-Methylenebis(4-methoxyphenyl)salicylidene and
N-(2,2'-Methylenebis(4-methoxyphenyl)-2-oxonaphthalidene-methylamine
HAKAN DAL
Department of Chemistry, Faculty of Science, Anadolu University, 26470 Yenibaglar, Eskisehir, Turkey
Corresponding author: Fax: +90 222 3204910; Tel: +90 222 3350580; E-mail: hakandal@anadolu.edu.tr
Received: 20 November 2013;
Accepted: 20 February 2014;
Published online: 28 April 2014;
AJC-15115
The new Schiff bases (4 and 5) were synthesized respectively from the reaction of 2,2'-methylenebis(4-aminomethoxybenzene) (3) with
salicylaldehyde and 2-hydroxy-1-naphthaldehyde. The products have been characterized by elemental analysis, FTIR, UV-visible and
NMR techniques. The tautomeric equilibria of 2-hydroxy Schiff bases were investigated in polar, non-polar, acidic and basic media by
using UV-visible absorption spectra. Compound 4 is in, predominantly, phenol-imine (O-H···N) form, whereas compound (5) is in
tautomeric equilibria (phenol-imine, O-H···N and keto-amine, O···H-N forms) in polar and non-polar solvents, as supported by 1H NMR
and UV-visible data. All of the NMR assignments were made using 1H, 13C NMR and aided by 2D COSY, NOESY, HETCOR and HMBC
heteronuclear correlation techniques. In addititon, theoretical calculations have been carried out PM6 methods in the MOPAC2009 and
Marvinbeans-5_3_01-windows programs. The heat of formation (∆Hf), enthalpy (∆H), entropy (∆S) Gibbs free energy (∆G), conformations
and tautomers of the synthesized compounds are estimated by using MOPAC2009 (PM6) program.
Keywords: Schiff bases, Tautomerism, Hetcor, HMBC, UV-visible, Theoretical calculation.
UV-visible10,13,14, 15N NMR17,20,24, 1H NMR 17,18,21-23, 13C NMR16,18-
INTRODUCTION
20,24 and X-ray crystallography techniques5,10,11,19,22,24 in solution
Schiff bases and their metal complexes have attracted
and in solid state. On the other hand, experimental results are
more attention due to their pharmacological properties as anti-
supported by theoretical calculations on the tautomeric forms
bacterial, antifungal, anticancer and antiviral agents1-6. Photo-
of the ortho-hydroxy Schiff bases25-28
.
chromism is another characteristic of these materials leading
to its application in various areas such as electronic display
systems, optical switching devices, information storage and
optical computers7-9.
In this study, we report (i) the synthesis of compounds 3,
4 and 5 (Fig. 1), (ii) spectroscopic characterizations of the new
compounds (4 and 5) in order to establish the hydrogen bonding
and tautomerism and (iii) theoretical calculations. In addition,
total assignments of 1H and 13C NMR spectra for the structure
are unambiguously made with the help of H-H correlation
spectroscopy (H-H COSY), as well as heteronuclear chemical
shift correlation (HETCOR) and heteronuclear multiple-bond
correlation (HMBC).
In view of the importance and also the usefulness of these
compounds, the chemists are prompted to generate the deri-
vatives by introducing different substituents. The presence of
ortho hydroxy group, for instance, has been regarded as one
of the important elements which favours for the existence of
intramolecular hydrogen bonding (O-H···N and O···H-N) and
also the tautomerism which accounts for the formation of either
phenol-imine or keto-amine tautomers10-12. In 2-hydroxy Schiff
bases strong hydrogen bonds between the OH groups and the
imine nitrogens are formed. In some instances, the hydrogen
atom of the OH is completely transferred to the imine nitrogen,
causing photochromism10,13. In other words, phenol-imine
keto amine equilibrium shifts predominantly to the
EXPERIMENTAL
2-Hydroxybenzaldehyde, 2-hydroxy-1-naphthaldehyde,
4-nitrophenol, hydrazine hydrate (95 %), NaH, Pd-C (5 %)
and iodomethane were purchased from Fluka and used without
further purification. Benzene, methanol, THF and DMSO were
used by redistallated. Melting points were measured on a Sanyo
Gallenkamp apparatus using a capillary tube. Elemental analyses
(C, H and N) were performed using a Vario EL III CHNS
elemental analyzer. UV-visible spectra were measured with
keto-amine side10,13-16,19,20. This type of tautomerism in 2-
hydroxy Schiff bases have been investigated using IR10,17,21-23
,

2760 Dal
Asian J. Chem.
OCH
OCH
OCH
OCH
OH
NO
OH
NO
3
3
3
3
1) NaH
Pd/ C
NH2NH2.H2O
2) CH3I/ DMSO
NO
NO
NH
NH
2
2
2
2
2
2
(1)
(2)
(3)
OCH
OCH
N
3
3
OCH
OCH
3
3
CH
2
CH
2
salicylaldehyde/MeOH
N
N
H
O
H
O
N
HC
CH
H
O
HC
CH
H
O
OCH
OCH
3
3
(4-e)
(4-k)
OCH
OCH
3
3
OCH
OCH
NH
NH
3
3
2
2
CH
2
CH
2
(3)
2-hydroxy-1-naphthaldehyde/MeOH
N
H
N
N
H
N
H
O
HC
CH
H
O
HC
CH
O
O
(5-e)
(5-k)
Fig. 1. Synthesis of compound 3, 4 and 5 (e: Phenol-imine, k: Keto-amine)
Shimadzu 3150 spectrophotometer using 1 cm Quartz cell.
1H and 13C NMR, COSY, HMBC and HETCOR spectra were
obtained on a Bruker 500 MHz Ultrashield Spectrometer
equipped with a 5 mm PABBO BB-inverse gradient probe.
The concentration of solute compounds was ca. 150 mg in
1 mL CDCl3 and DMSO-d6. Standard Bruker pulse programs29
were used in the experiments. FTIR spectra were recorded on
a Perkin Elmer Spectrum 100 FTIR spectrometer in KBr discs.
The CS Chemoffice30 and the MOPAC200931 programs were
used for the calculation of the physicochemical properties of
the molecules. All the molecules were drawn by the CS
ChemDraw and then minimized by the MM2 method in the
CS Chem 3D program. Their theoretical calculations in aqueous
phase was carried out using the new semiempirical PM6
quantum chemical methods in the MOPAC2009 program.
2,2'-Methylenebis(4-nitrophenol) (1): 2,2'-Methylenebis (4-
nitrophenol) was prepared according to the published procedure26.
2,2'-Methylenebis(4-nitromethoxy benzene) (2): The
reaction of 1 (5.32 g; 18 mmol) and NaH (1.44 g, 24 mmol) in
THF produced sodium[2,2'-methylenebis(4-nitrophenolate)].
A solution of sodium[2,2'-methylenebis(4-nitrophenolate)]
(3.34 g; 10 mmol) used as prepared in DMSO (100 mL) and
then iodomethane (2.84 g; 20 mmol) was added dropwise to
this solution with stirring. The reaction mixture was maintained
at reflux for 8 h and then cooled to room temperature, forming
a yellow precipate.
The yellow residue was filtered and washed with water
(50 mL). The white-yellow solid was dried under vacuo, yield
3.88 g (67 %), m.p. 186 °C. Elemental analysis calcd. for
C15H14N2O6: C, 56.60; H, 4.43; N, 8.80. Found: C, 56.51; H, 3.72;
N, 8.60. IR (KBr, νmax, cm-1): Ar-H(asym.) 3070 w, Ar-H(sym.) 3027
w, C=C 1589 vs, NO2 1517 s, 1343 vs, C-O-(arom.) 1268 s.
2,2'-Methylenebis(4-aminomethoxy benzene) (3): To
the mixture of 2,2'-methylenebis(4-nitromethoxybenzene) (2)
(5.01 g; 15 mmol) and Pd-C catalyst (0.25 g) in dry ethanol
(150 mL), hiydrazine hydrate (5 mL) was added dropwise with
stirring. The mixture was maintained at reflux for 10 h and
then allowed to an ambient temperature. The reaction mixture
was filtrated and the solvent was removed. The crude white-
solid product was crystallized in ethanol.Yield 2.30 g, (57 %),
m.p. 128 °C. Elemental analysis calcd. for C15H18N2O2: C,
69.74; H, 7.02; N, 10.84. Found: C, 69.72; H, 6.47; N, 10.79
IR (KBr, νmax, cm-1): NH2 3400 m, Ar-H(sym.) 3030 w, 3000 w,
Ar-H(asym.) 3080 w, C=C 1600 vs, C-O-(arom.) 1234 s.
N-[2,2'-Methylenebis(methoxyphenyl)]salicylidene (4):
A solution of 2,2'-methylenebis(4-aminomethoxybenzene) (3)
(2.58 g; 10 mmol) and 2-hydroxybenzaldehyde (10 mmol,
1.1 mL) in methanol on the ice bath was stirred for 4 h. The
precipitated solid was filtrated and then it was recrystallized
from methanol. Yield 3.50 g (75%), m.p. 182 °C. Elemental
analysis calcd. for C29H26N2O4: C, 74.66; H, 5.62; N, 6, Found:
C, 75.32; H, 5.43; N, 6.15. IR (KBr, νmax, cm-1) NH 3435 s,

Vol. 26, No. 9 (2014)
Intramolecular Hydrogen Bonding and Tautomerism in Schiff Bases 2761
Ar-H(asym.) 3056 w, Ar-H(sym.) 3010 w, C=N 1620 vs, C=C 1598
vs, C-O-(arom.) 1252 s. ESI-MS: 467 [M + H]+.
4000-3500 cm-1 region was not observed in the IR spectrum
for compound (5). This observation implies that the H atom
from the O-H group in compound migrates to azomethine N
atom via keto-amine form (N-H···O) intramolecular hydrogen
bonding in the solid state.
N-[2,2'-Methylenebis(methoxyphenyl]-2-oxonaphtha-
lidenemethylamine (5): A solution of 2,2'-methylenebis(4-
amino methoxybenzene) (3) (2.58 g; 10 mmol) and 2-hydroxy-
1-naphthaldehyde (1.72 g; 10 mmol) in methanol on the ice
bath was stirred for 5 h. The precipitated solid was filtrated
and then it was recrystallized from methanol. Yields 4.10 g
(72 %), m.p. 193 °C. Elemental analysis calcd. for C37H30N2O4:
C, 78.43; H, 5.34; N, 4.94, Found: C, 78.70; H, 4.92; N, 5.33.
IR (KBr, νmax, cm-1) NH 3435 s, Ar-H(asym.) 3046 w, Ar-H(sym.)
3023 w, C=N 1623 vs, C=C 1564 vs, C-O-(arom.) 1250 s. ESI-
MS: 567.1 [M + H]+.
UV-visible studies: The Schiff bases show absorption
in the range greater than 400 nm in polar and nonpolar
solvents10,13,19,28. The UV-visible spectra of the compounds (4
and 5) were found to be useful in understanding the degree of
stabilization upon these series of phenol-imine and keto-amine
tautomers10,11
.
The UV-visible spectra of the compounds (4 and 5) were
studied in polar and non-polar solvents in both acidic
(CF3COOH) and basic (NEt3) media. In solutions, the expected
tautomeric species are illustrated in Fig. 2 and the calculated
keto-amine forms are given in Table-1, which are estimated
from the following equations: A2/A1 = x/(100-x) where,
A1 = the absorbance of the phenol-imine tautomer (π→π*),
A2 = the absorbance of the keto-amine tautomer (n→π*),
x = the percentage of keto-amine tautomer. The electronic
absorbtion spectra of compound 5 displays four mean bands
(Fig. 3). The first (210-234 nm) and the second (240-281 nm)
bands are assigned to the π→π* transitions of aromatic rings.
The third band (301-334 nm) also indicates π→π* transitions
RESULTS AND DISCUSSION
The FTIR spectra of compounds 2-5 exhibit two medium
intensity absorptions at 3077-3060 and 3030-3000 cm-1 attri-
buted to the asymmetric and symmetric stretching vibrations
of the aromatic C-H bonds. The characteristic ν(NH2) (3400
and 3211 cm-1) stretching bands of compound 3 disappear in
the spectra of compounds 4 and 5.
The characteristic ν(C=N) absorption bands were observed
at 1620 and 1623 cm-1 for compounds (4) and (5). The observa-
tion of aromatic ν(C-O) at 1305 cm-1 and the O-H stretch at
H
O
H
N
N
H
C
H H
O O
C
H
N
N
H
C
H H
O O
C
N
N
H
C
C
H
O
H
(D)
(A)
(C)
phenol-imine / phenol-imine
O-H---N /--
phenol-imine / phenol-imine
O-H---N / O-H---N
E form / E form
phenol-imine / keto-amine
O-H---N / O---H-N
E form / --
E form / Z form
H
H
O
H
O
O
N
N
H
N
N
H
N
N
H
C
C
H H
O O
C
H
O
C
C
C
H
H
H
(E)
(B)
(F)
phenol-imine / phenol-imine
-- / --
keto-amine / keto-amine
O---H-N / O---H-N
-- / --
phenol-imine / keto-amine
-- / O---H-N
Z form / Z form
Z form / --
OCH3
OCH3
CH2
: Naphthaldimine
Fig. 2. Expected tautomeric species of 4 and 5 in solutions

2762 Dal
Comp.
Asian J. Chem.
TABLE-1
EFFECTS OF SOLVENT, ACIDIC AND BASIC MEDIA ON THE UV SPECTRA OF COMPOUNDS (4) AND (5)
λ, nm (ε, M-1cm-1)
Keto-amine isomer (%)
Solvent
Solvent Acidic Basic
media mediaa mediab
Solvent media
354.0(34760)
352.0(38400)
355.0(40960)
Acidic mediaa
Basic mediab
DMSO
324.5(22800), 282.0(16160) Not measured
327.5(16120), 282.0(13080) 354.0(60920)
397.5(60960), 277.0(47280) 353.5(50400), 299.0(41240)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
EtOH
(4) CHCl3
Benzene
354.5(41840), 276.5(25120) 400.0(56040), 279.0(35240) 353.5(46440)
Not measured 352.0(31240)
447.5(21760), 395.0(29280) 355.5(25760), 316.0(31720) Not measured
341.5(20440), 327.5(22600) 282.5(19960)
Cyclohexane 352.0(36080)
-
49.0
DMSO
468.0(27000), 449.0(31040)
363.0(21640), 340.0(21680) 357.5(10720), 317.5(15040) 394.0(20600), 340.0(15480)
324.5(23560) 273.5(13440) 326.0(16680)
449.0(30040), 390.5(37840) 444.5(69320), 378.0(31520) 449.5(30720), 386.0(47160) 52.0
340.0(28040), 325.0(30920) 340.0(35440), 325.0(39120)
389.0(34440), 342.0(20400) 442.5(57400), 377.5(27080) 386.5(42400), 342.0(24200)
467.0(14240), 449.0(16400) 59.0
-
47.0
EtOH
(5)
69.0
68.0
-
51.0
CHCl3
-
-
-
-
Benzene
326.0(20680), 275.5(19760) 276.0(21920)
384.5(36400), 340.0(21880) Not measured
Cyclohexane 323.5(21960)
326.0(23760)
385.5(55640),340.5(32680)
324.5(32200)
A2/A1=x/(100–x) where, A1 = The absorbance of the phenol-imine isomer (π-π*); A2= The absorbance of the keto-amine isomer (n-π*); x = The
percentage of keto-amine isomer. aCF3COOH, b(C2H5)3N
2.0
1.5
1.0
0.5
0
2.0
1.5
1.0
0.5
0
2.0
1.5
1.0
0.5
0
(a)
(b)
(c)
270
400
Wavelength (nm)
500
600
270
400
Wavelength (nm)
500
600
270
400
Wavelength (nm)
500
600
Fig. 3. UV-visible spectra of compound 5. DMSO , ethanol , chloroform , benzene , cyclohexane . (a) pure solvent, (b) acidic (CF3COOH) and
(c) basic (NEt3) solutions
1
of aromatic rings and appears to be splitted two bands in the
spectrum of compound 5 where the C=N groups are involved
in intramolecular hydrogen bonds. The bands at 325-396 nm
can be assigned to an intramolecular π→π* transitions of the
C=N groups. The Schiff bases show absorptions n→π* in the
lists complete H and 13C NMR assignments in CDCl3 for
compounds 4 and 5. The expected tautomeric species and
geometric isomers (E and Z) of the Schiff bases compounds
1
(4 and 5) in solutions are depicted in Fig. 2. The H signals
were assigned on the basis of chemical shifts, multiplicities
and coupling constants. In the solution, the compounds have
symmetric structures according to 1H NMR spectra.
range greater than 400 nm in polar and non-polar solvents23,28
.
It should be pointed out that the new band belongs to the keto-
amine form of the Schiff bases with OH group in ortho position
to the imine group11,14. The band is observed at > 400 nm
in pure solvents (DMSO, EtOH and CHCl3), in CHCl3 and
benzene in acidic media and in basic media of solvents EtOH
and CHCl3 for compound 5. Whereas this band is not observed
for compound 4 in all of the solutions indicating that the only
phenol-imine tautomers are present in the solutions. The keto-
amine isomer ratios of compound 5 are given in Table-1. The
results imply that the solvent polarities and the addition of
CF3COOH are considerably effective on the tautomeric equilibria.
NMR Studies: Proton magnetic resonance spectroscopy
is a helpful tool for the identification of organic compounds
in conjunction with other spectrometric information. Table-2
The peaks at 7.10 (d, 2H), 7.03 ppm (d, 2H), 7.20 ppm
(dd, 2H), 7.38-7.33 ppm (m, 2H) and 6.90-6.96 ppm (m, 2H)
are assigned to be Ha, Hb, Hc, Hd-Hf and He-Hg, respectively,
for 4 and 7.17 (d, 2H), 6.98 ppm (d, 2H), 7.27 ppm (dd, 2H),
7.72 ppm (d, 2H), 7.33 (td, 2H), 7.51 (td, 2H), 8.06 (dd, 2H),
7.08 (d, 2H) and 7.77 (d, 2H) are assigned to be Ha, Hb, Hc,
Hd, He, Hf, Hg, Hh and Hi respectively, for compound 5, which
have H-H correlation in H-H COSY and NOESY spectra (Figs.
4 and 5). The signals at δ = 13.21 ppm (s, 2H) for compound
4 and at δ = 15.55 ppm (d, 2H) for compound 5 which can not
been found any proton-proton correlative signal in H-H COSY
spectrum and any proton-carbon signal in HETCOR spectrum
(Fig. 6), are assigned to the proton of hydroxy groups. Assign-

Vol. 26, No. 9 (2014)
Intramolecular Hydrogen Bonding and Tautomerism in Schiff Bases 2763
TABLE-2
1H NMR AND 13C NMR SPECTRAL DATA IN CDCL3. CHEMICAL SHIFTS (δ) ARE REPORTED IN ppm,
AND s: SINGLET, d: DOUBLET, dd: DOUBLE DOUBLET, m: MULTIPLIED, t: TRIPLET
CH3
CH3
O
O
CH3
CH3
3
Hb
4
O
O
2
3
5
Hb
4
2
1
Ha
Hc
6
N
5
N
HC
CH Hd
13
1
Hc
Ha
6
7
12
14
OH HO
He
8
N
N
HC
CH
7
15
9
Hf
Hi
11
16
12
OH HO
Hd
11
He
10
Hh Hg
8
(5)
9
Hg
10
Hf
(4)
Compound
4
5
Ha
Hb
Hc
Hd
He
Hf
Hg
Hh
7.10 (d, 2H), [4JHa-Hc= 2.63 Hz]
7.17 (d, 2H), [4JHa-Hc = 2.71 Hz]
7.03 (d, 2H), [3JHb-Hc= 8.38 Hz]
6.98 (d, 2H), [3JHb-Hc = 8.68 Hz]
7.20(dd, 2H),[3JHc-Hb= 8.38 Hz, 4JHc-Ha= 2.63 Hz]
7.27 (dd, 2H), [3JHc-Hb = 8.68 Hz, JHc-Ha = 2.71 Hz]
4
7.38-7.33 (m, 2H)
6.90-6.96 (m, 2H)
7.38-7.33 (m, 2H)
6.90-6.96 (m, 2H)
-
-
7.72 (d, 2H), [3JHd-He = 7.52 Hz]
7.33 (td, 2H), [3JHe-Hdf = 7.45 Hz, 4JHe-Hg = 1.11 Hz]
7.51 (t, 2H), [3JHf-Heg = 7.15 Hz]
8.06 (dd, 2H), [3JHg-Hf = 8.44 Hz, JHg-He = 1.09 Hz]
4
7.08 (d, 2H), [3JHh-Hi = 9.16 Hz]
Hi
7.77 (d, 2H), [3JHi-Hh = 9.16 Hz]
CH
CH2
CH3
OH
C1
C2
C3
C4
C5
C6
C7
C8
C9
C10
C11
C12
C13
C14
C15
C16
CH
CH2
CH3
8.57 (s, 2H)
4.05 (s, 2H)
3.90 (s, 6H)
13.21 (s, 2H)
123.3
132.6
156.9
117.1
119.8
131.8
119.5
161.0
118.9
131.9
110.9
129.8
-
9.32 (d, 2H), [3JCH-NH = 4.5 Hz]
4.12 (s, 2H)
3.96 (s, 6H)
15.55 (d, 2H)
122.8
130.0
156.6
111.2
118.7
137.9
108.7
170.1
136.2
122.3
127.2
133.2
129.3
123.3
127.9
-
-
-
118.9
153.4
30.1
55.9
160.3
30.0
55.8
s, singlet; d, doublet; dd, doublet of doublet; t, triplet; m, multiplet
ments of the protons and carbons were made by two dimen-
sional heteronuclear-correlated experiments (HETCOR) using
delay values which corresponds to 1J(C, H), HMBC using delay
values which corresponds to 2J(C, H) or 3J(C, H) between the
carbons and protons (Fig. 7, Table-3). The signals appeared
as a singlet at δ = 8.57 ppm for compound 4 and doublet 9.32
ppm (d, 2H, 3JCHNH = 4.5 Hz) for compound 5 can be ascribed
to CH=N. The singlets (CHN and OH) are observed for
compound 4 in CDCl3 and DMSO show the existence of only
phenol-imine tautomer (E/E isomer in Fig. 2, form A). The
doublets (CHN and OH) are observed for compound 5 indicate
keto-amine tautomer (N-H···O, hydrogen bond) present in the
solution (Fig. 2, form B, Fig. 8). A singlet assignable to the
chemically and magnetically equivalent protons in methoxy
group of phenyl ring were observed at δ = 3.90 ppm for
compound 4 and δ = 3.96 ppm for compound 5. The singlets
are observed at δ = 4.05 and δ = 4.12 ppm for the Ar-CH2-Ar
protons of compounds 4 and 5, indicated that they are equi-
valent. Ha-Hi protons are easily distinguishable and assignable
by using HMBC methods (Table-3, Fig. 7).
All of the possible carbon peaks are observed from the
proton decoupled 13C NMR spectra of compounds 4 and 5. As
expected, the compounds seem to have symmetric molecular
structures in solution (Table-2). The assignments of aromatic
carbon atoms were done in the first step by one-bond proton-
carbon correlations observed in HETCOR spectra (protonated
carbon atoms) and in the second step by long range correlations
found HMBC spectra. Assignments of the protonated carbons
were made by two dimensional heteronuclear-corre lated
experiments (Figs. 6 and 7) using delay values which corres-
pond to 1J(C, H). As an example, only the HETCOR spectrum
of compound 5 is depicted in Fig. 6.

2764 Dal
Asian J. Chem.
TABLE-3
2D COSY AND NOESY (1H-1H CORRELATION), HETCOR AND HMBC (1H-13C CORRELATION) FOR COMPOUND 5
HETCOR (COSY)
1J
HMBC [J(C,H)]
NOESY
intraJ
Atom
2J
3J
4J
intraJ
Ha
Hb
Hc
Hd
He
Hf
Hg
Hh
Hi
C1
-
C3, C5
C2, C6
C3
-
-
-
C12
-
C15
C6, C14, C16
-
C1
-
-
C15
-
-
C7, C10
C16
-
CH
-
-
-
CH
C16
C7
Hh, Ha, CH
Ha, He, Hc
Hb, Hg, CH
He, Hf,
Hb, Hc, Hd, Hf CH
Hd, He
Hc
Ha, Hd, Hi
Hh
C4 (Hc)
C5 (Hb)
C8 (He, Hf)
C9 (Hd,Hf)
C10 (Hg,He)
C11 (Hf)
C12 (Hi)
C13 (Hh)
CH
C3
C6
C16
C10
-
C15
C15
C14
C7
-
C8, C10
C15
CH
Ha, Hc, He
Intra; intramolecular interaction
C13 C8C10C9C1C12
C11
C4
CH
Hg
Hi Hd
Hf
He Hc Ha Hh Hb
C5
ppm
ppm
6.5
6.9
7.0
7.1
Hb
Hh
Ha
7.0
7.5
8.0
8.5
9.0
9.5
7.2
7.3
7.4
7.5
7.6
7.7
7.8
7.9
8.0.
8.1
Hc
He
Hf
Hd
Hi
Hg
CH
8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9
ppm
165 160 155 150 145 140 135 130 125 120 115 110
ppm
Fig. 4. COSY spectrum of compound 5
Hg
Hi Hd HfHeHcHaHhHb
Fig. 6. HETCOR spectrum of compound 5
CH
The signals at δ 122.8, 111.2, 118.7, 170.1, 136.2, 122.3,
127.2, 133.2, 129.3, 153.4, 30.1 and 55.9 ppm assign them to
C1, C4, C5, C8, C9, C10 C11, C12, C13, CH, CH2 and CH3
carbon atoms (Table-2). In compound 5, the absence of any
contours at δ 130, 156.6, 137.9, 108.7 and 170.1 ppm assign
them to the C2, C3, C6 C7 and C8 carbon atoms, respectively.
On the other hand, the nonprotonated carbons C2, C3, C6 C7
and C14 of compound 5 were also determined using delays in
the two dimensional HMBC experiment to emphasize the long
range coupling, either 2J(C,H) or 3J(C,H) between the carbons
and protons (Fig. 7, Table-3).
Theoretical calculation: Theoretical calculations are
carried out using PM6 methods in the MOPAC200930. Initial
estimates for the geometries of all are obtained by a molecular
mechanics program (ChemBioOffice Ultra 2010 forWindows)
followed by full optimization of all geometrical variables (bond
lengths, bond angles and dihedral angles), without any symmetry
constraint31.
ppm
7.0
7.2
7.4
7.6
7.8
8.0
8.2
8.4
8.6
8.8
9.0
9.2
9.4
The results of theoretical calculations for compounds 4
and 5 are listed in the Tables 4-6.
ppm
9.6 9.4 9.2 9.0 8.8 8.6 8.4 8.2 8.0 7.8 7.6 7.4 7.2 7.0
Fig. 5. NOESY spectrum of compound 5

Vol. 26, No. 9 (2014)
Intramolecular Hydrogen Bonding and Tautomerism in Schiff Bases 2765
(a)
(b)
8.4 8.3 8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9
9.60 9.55 9.50 9.45 9.40 9.35 9.30 9.25
15.6
16.0
15.8
Fig. 8. 1H-NMR spectra of compound 5 at δ 6.8-16.2 ppm, (a) in CDCl3 and (b) in DMSO
CH
Hg Hi Hd He HcHaHh Hb
Tautomer calculation: The effects of the solvents on
Hf
tautomer equilibria have been examined by the calculatins.
Though, it is found out that the experimental results of com-
pound 4 have not been shown the tautomer, it has shown that
solvents other than water the phenol-imine and keto-amine
tautomer equilibrium in theoretical calculation. It was found
to be the predominant form of keto-amine for compound 5 in
theoretical calculations (Table-4, Fig. 1).
Isomer calculation: All forms of the isomers in Fig. 2
have been studied for different solvent phases (H2O, DMSO,
EtOH, CHCl3, benzene, cyclohexane) (Tables 5 and 6). The
stable isomer forms have been determined by ∆Gf energies.
The isomers listed in accordance with ∆Gf stabilities in all
solvent phases (Table-6). It is observed that stabilities of the
ppm
C7
C4
110
120
130
140
150
160
170
ppm
C5
C11
C12
C1
C15
C2
C9
C10
C8
C16
C6
C13
CH
C3
C14
9.69.4 9.2 9.08.88.68.48.28.07.8 7.67.47.27.06.8
Fig. 7. HMBC spectrum of compound 5
TABLE-4
PM6 CALCULATION OF TAUTOMERIC EQUILIBRIUM CONSTANTS pKT IN LIQUID PHASE
Compound
∆Hf
∆H
∆S
∆Gfa
∆Gb
δ∆Gfc
KT
pKT
d
e
H2O
-120.728
37.567
-91.898
-102.557
DMSO
4e
4k
5e
5k
-53.484
98.466
-19.221
-31.329
21528.572
20657.504
24933.050
24601.233
225.651
204.358
243.882
239.020
-45.715
-40.241
-47.744
-46.627
158.295
-10.659
6.57E+07
-7.820
4e
4k
5e
5k
-52.702
-63.651
-21.670
-41.350
21719.700
21529.600
25196.000
24690.500
223.544
223.129
254.051
244.233
-119.318
-130.144
-97.377
-114.131
EtOH
-44.896
-44.963
-50.511
-48.091
-10.826
-16.754
8.72E+07
1.94E+12
-7.940
-12.280
4e
4k
5e
5k
-52.117
-62.715
-21.050
-40.515
21692.729
21510.285
25181.279
24686.990
223.264
222.947
254.177
244.186
-118.650
-129.153
-96.795
-113.282
CHCl3
-44.840
-44.928
-50.563
-48.080
-10.504
-16.488
5.06E+07
1.24E+12
-7.700
-12.093
4e
4k
5e
5k
-47.678
-55.762
-16.331
-34.256
21542.510
21398.700
25007.170
24664.190
225.439
222.067
251.586
245.957
-114.859
-121.938
-91.304
-107.551
Benzene
-110.252
-115.984
-85.796
-101.475
Cyclohexane
-108.627
-113.721
-84.477
-45.638
-44.777
-49.965
-48.631
-7.079
1.55E+05
8.27E+11
-5.190
-16.248
-11.910
-42.949
-48.624
-11.273
-27.713
21414.968
21309.743
24852.617
24658.970
225.848
226.040
250.076
247.525
-45.888
-46.050
-49.670
-49.103
-5.732
4e
4k
5e
5k
1.60E+04
3.16E+11
-4.200
-15.680
-11.500
4e
4k
5e
5k
-41.910
-47.098
-10.158
-26.295
21390.137
21273.996
24821.584
24608.234
223.884
223.568
249.394
249.612
-45.327
-45.349
-49.498
-49.776
-5.094
5.44E+03
7.65E+11
-3.730
-16.202
-11.880
-100.679
δ∆
a∆Gf = ∆Hf - T∆S; b∆G = ∆H - T∆S; cδ∆Gf = ∆Gf(k) - ∆Gf(e); dKTf = e(- Gf/RT); epKT(f) = -log KTf; R = 1.987 × 10-3 kcal/mol K and T= 298 K

2766 Dal
Asian J. Chem.
TABLE-5
with decreasing solvent polarity (H2O > DMSO > EtOH >
CHCl3 > benzene > cyclohexane) (Table-6). It was mentioned
before that the phenol-imine and keto-amine equilibrium of
compound 5 shifts to keto-amine form (Table-4). The B isomer
written keto-amine/keto-amine on both sides of the compound
forms the most stable isomer compound 5. Besides, B has two
H-bondings. C and F isomers which are the phenol-imine/
keto-amine forms of compound 5 are, respectively in second
and third place in stability order. C isomer having two H-
bondings is more stable than F isomer. On the other hand, two
H-bondings having phenol-imine/phenol-imine on both sides
in isomer A has been observed for compound 5 and it is
rationale to be in fourth place in stability. Though, the molecule
is in phenol-imine/phenol-imine structure in isomer D, isomer
has one H-bonding and this causes the less stability.Although,
the molecule is again in phenol-imine/phenol-imine structure
in E isomer form, it has been determined as the least stable
isomer since it does not have the H-bonding (Table-6).
PM6 CALCULATION OF THE TAUTOMERIC SPECIES OF
COMPOUND 5 MOLECULES IN LIQUID PHASE
Compd.
∆Hf
∆H
∆S
∆Gf
∆G
H2O
-23.872 24971.278 248.4773 -97.918
-41.818 24816.816 246.9922 -115.422 -48.787
-49.075
A
B
C
D
E
F
-32.7
-23.73
50.945
24877.329 248.1514 -106.649 -49.072
25025.802 248.9132 -97.906
26098.676 259.7981 -26.475
-49.150
-51.321
-33.552 24695.657 240.9281 -105.349 -47.101
DMSO
-23.557 24917.415 248.592
-41.425 24787.696 247.050
-32.386 25072.149 250.703
-23.380 24964.903 247.160
26079.158 258.706
-33.239 24698.025 241.084
EtOH
-97.637
-115.046 -48.833
-107.095 -49.637
-97.034
-25.728
-105.082 -47.145
-49.163
A
B
C
D
E
F
-48.689
-51.015
51.366
-22.951 24898.449 248.242
-40.585 24786.514 248.009
-31.677 25055.435 250.913
-22.612 24961.330 247.201
26068.051 258.933
-32.557 24691.892 241.318
CHCl3
-96.927 -49.078
-114.492 -49.120
-106.449 -49.717
-96.278
-24.874
-104.470 -47.221
A
B
C
D
E
F
Conclusion
The absorption band at 400 nm belongs to the keto-amine
form of the Schiff bases. The keto-amine tautomer was always
observed when the Schiff base was derived from 1-hydroxy
naphthaldehyde and aromatic amine. Whereas, in Schiff bases
derived from salicylaldehyde and aromatic amine the keto-
amine form was not observed in polar and non-polar solvents,
but it was observed in acidic media13,15. Compounds 4 and 5
were in tautomeric equilibria (enol-imine, O-H···N keto-amine,
O···H-N forms) in solvents, acidic chloroform and benzene
solutions and basic dimethyl sulfoxide, chloroform and
benzene. 1H NMR data for compounds 4 and 5 show that the
tautomeric equilibria favors the phenol-imine and keto-amine
forms, respectively, in CDCl3 and DMSO (Fig. 8).
Both of the compounds 4 and 5, appear to be the tetra-
dentate ligands, having two N and two O donor atoms, for
transition metal cations. They can produce coloured complex
dye in solutions and solid state. Preliminary results obtained
from the reaction of compound 4 and Ni(II) cation can prove
this proposal. On the other hand, compounds 4 and 5 illustrated
significant antifungal activities against tested yeast strains. But,
in general they were inactive against bacteria in exception of
S. aureus for compound 5. Consequently, for developing new
antifungal agents both of the compounds could be lead for
further studies.
-48.705
-51.094
52.288
-18.361 24815.974 248.596
-34.276 24736.642 249.497
-26.329 24923.163 251.687
-16.790 24991.491 247.513
26021.752 263.418
-27.385 24632.318 242.751
Benzene
-92.443 -49.266
-108.626 -49.613
-101.332 -50.080
-90.549
-19.145
-99.725
A
B
C
D
E
F
-48.767
-52.477
-47.707
59.354
-13.468 24712.820 247.165
-27.672 24671.921 249.785
-20.606 24681.141 249.480
-10.592 24902.684 250.996
25956.210 264.629
-20.674 24541.178 243.075
Cyclohexane
-87.123
-102.108 -49.764
-94.951
-85.389
-11.849
-93.110
-48.942
A
B
C
D
E
F
-49.664
-49.894
-52.903
-47.895
67.010
-12.392 24677.381 248.301
-26.236 24640.812 250.668
-19.446 24732.339 250.943
24892.044 249.221
25926.437 264.835
-20.674 24541.178 243.075
-86.386
-100.935 -50.058
-94.227
-83.506
-10.215
-93.110
-49.316
A
B
C
D
E
F
-50.049
-49.376
-52.994
-47.895
-9.238
68.706
a∆Gf = ∆Hf - T∆S; b∆G = ∆H - T∆S
In the theoretical calculations, the effects of the solvent
on tautomer equilibria and isomer stabilities have been investi-
gated. Except the water phase, compound 4 shows the phenol-
imine and keto-amine tautomer equilibria. Compound 5 has
the keto-amine tautomer, predominantly in the equilibria accor-
isomers in all solvents have been in the same parallels. The
declining stability of isomer forms in the the same solvent
was determined as B > C > F > A > D > E. According to the
solvent effect, the stability exhibits the decrease in parallel
TABLE 6
GIBB’S FREE ENERGIES FOR THE TAUTOMERIC SPECIES OF COMPOUND 5 IN SOLUTIONS
Compound
H2O
Compound
DMSO
Compound
EtOH
Compound
CHCl3
Compound
Benzene
Compound
∆Gf
∆Gf
∆Gf
∆Gf
∆Gf
∆Gf
Cyclohexane
B
C
F
A
D
E
-115.422
-106.649
-105.349
-97.918
-97.906
-26.475
B
C
F
A
D
E
-115.046
-107.095
-105.082
-97.637
-97.034
-25.728
B
C
F
A
D
E
-114.492
-106.449
-104.47
-96.927
-96.278
-24.874
B
C
F
A
D
E
-108.626
-101.332
-99.725
-92.443
-90.549
-19.145
B
C
F
A
D
E
-102.108
-94.951
-93.110
-87.123
-85.389
-11.849
B
C
F
A
D
E
-100.935
-94.227
-93.11
-86.386
-83.506
-10.215

Vol. 26, No. 9 (2014)
Intramolecular Hydrogen Bonding and Tautomerism in Schiff Bases 2767
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