The synthesis, characterization, acid dissociation, and theoretical calculation of several novel benzothiazole Schiff base derivatives

Article abstract of DOI:10.1021/je500679w

Schiff base derivatives of benzothiazoles were synthesized using substituted 2-aminobenzothiazoles and different substituted benzaldehydes. The structures of the synthesized Schiff bases were determined using Fourier transform infrared spectroscopy,

Full text of DOI:10.1021/je500679w

Article
pubs.acs.org/jced
The Synthesis, Characterization, Acid Dissociation, and Theoretical
Calculation of Several Novel Benzothiazole Schiff Base Derivatives
̈
Kamuran Gorgun, Handan Can Sakarya, and Mujgan Ozkutuk*
̈
̈
̈
̈
̈
Faculty of Arts and Science, Department of Chemistry, Eskisȩ hir Osmangazi University, 26470, Eskisȩ hir, Turkey
S
* Supporting Information
ABSTRACT: Schiff base derivatives of benzothiazoles were
synthesized using substituted 2-aminobenzothiazoles and different
substituted benzaldehydes. The structures of the synthesized
Schiff bases were determined using Fourier transform infrared
1
spectroscopy, H NMR, 13C NMR, and elemental analyses. The
acid dissociation behavior, which was visible in UV−visible
absorption spectra, of the 10 novel benzothiazole Schiff bases was
studied. The acidity constants (pKa), the structures, and the
protonation mechanisms of the studied molecules were obtained.
The substituent effect on both phenyl rings of these synthesized
benzothiazole Schiff base derivatives was observed, and the
experimentally calculated deprotonation values were between
11.47 and 8.91, and the protonation values were between 4.54 and 3.52. Also, the protonation sites of synthesized benzothiazole
1
Schiff base were investigated using H NMR and FT-IR. The theoretical calculations were performed with the CACHE
semiempirical method (AM1, PM3, and PM5). The best correlation between the experimental and theoretical pKa and acidity
values of the compounds was obtained using the PM5 calculation method.
ometry,25,26 and similar methodologies have been proposed for
the experimental determination of acid dissociation constants.
In general, UV−vis spectroscopic methods are highly sensitive
1. INTRODUCTION
Schiff bases are compounds that include the azomethine group
(CHN) in their structure, which is generally synthe-
sized by the condensation of primary amines and active
carbonyl groups. 1,3-Benzothiazole derivatives, in general,
demonstrate various pharmacological properties1 and are used
as anti-inflammatory,2 antitumor,3−5 analgesic,6 and antimicro-
bial7 agents. These derivatives also have liquid crystal8−10 and
photovoltaic application11,12 properties. Their biological activity
has an important role in several fields of chemistry and
biochemistry.13−16 In addition, different substituted forms of
the benzothiazole ring at the C-2 position have diversified
therapeutic application9 and anticancer effects.10 Therefore, we
synthesized various Schiff bases including the benzothiazole
nucleus. Because of increasing interest in Schiff bases, the
number of studies and publications regarding their chemical
behavior, specifically the pKa values, has considerably
increased.17−19 Understanding the pKa value of a compound
provides information on its distribution, transport behavior,
receptor-binding behavior, and mechanism of action in certain
pharmaceutical preparations. This knowledge is available in the
quantitative treatment of systems involving acid−base equilibria
in solution as well. Acid dissociation constants are values that
can describe a molecule’s physicochemical properties, partic-
ularly, the extent of ionization of its functional groups with
respect to pH. Thus, the acid−base properties of chemical
substances are able to suggest their toxicity, pharmaceutical
activity, and analytical roles. Capillary electrophoresis,20 UV−
vis absorption,21−23 fluorescence spectrophotometry,24 potenti-
(can detect substances at concentrations as low as 10−6 M) and
are therefore suitable for chemical equilibria studies, even
though they are more time-consuming than the other
aforementioned spectroscopic methods.27 Additionally, the
UV−vis spectroscopic method is very useful if a compound
has a low solubility or its pKa values are highly acidic or basic.
The aim of this work is to determine the acid−base
dissociation constants of novel benzothiazole Schiff bases using
the UV−vis spectroscopic method. In this study, we first
synthesized novel benzothiazole Schiff bases. Second, we
determined the pKa values of compounds 3a−j and their acid
dissociation constants to elucidate structure−reactivity relation-
ships, which were also compared with calculated pKa values.
These acidity constants were confirmed by the UV−vis
spectroscopic method.
2. CALCULATION METHODS
An Intel Pentium Pro 400 MHz computer was used for all
calculations. The initial data for geometry optimization (bond
lengths, bond angles, and dihedral angles) were estimated by a
molecular mechanics program (CS ChemOffice Pro for
Microsoft Windows). The relative stability of the investigated
Received: July 31, 2014
Accepted: January 28, 2015
© XXXX American Chemical Society
A
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Scheme 1. General Scheme of the Synthetic Procedure for Compounds 3a−j
compounds was calculated in the aqueous phase by the
semiempirical molecular orbital theory Austin Method One
(AM1),28 Parametric Method 3 (PM3),29,30 and parametric
method 5 (PM5),31 which are well suited for geometrical
optimizations. The calculations were performed using the
CACHE 6.1 software.32
3.2. The Determination of Acidity Constants. For
determining the acid dissociation constant “pKa”, the
spectrophotometric method is one of the most commonly
applied methods.33 This method is based on the measurement
of absorbance to determine the concentration ratio of
protonated/deprotonated forms. The pKa values can be
calculated using the curves in Figure 1. Calculations of half-
3. RESULTS AND DISCUSSION
The obtained experimental and computed data are discussed in
the following sections.
3.1. Synthesis and Characterization. Title compounds
3a−j were synthesized according to the process described in
Scheme 1. The structures of compounds 3a−j were established
using elemental analysis, Fourier transform infrared spectros-
1
copy (FT-IR), H NMR, and 13C NMR.
The FT-IR spectra of benzothiazole Schiff bases 3a−j exhibit
one characteristic band in the range of 1605−1615 cm−1, which
can be assigned to (−CHN−). The existence of the aromatic
rings was demonstrated by the following bands: aromatic
carbon-H stretching υC−H (3045−3040 cm−1) and phenyl
ring stretching υC−C (1575−1500 cm−1).
1
In the H NMR spectra of novel benzothiazole Schiff bases
3a−j, the chemical shift of the aromatic protons was observed
in the 6.90−8.74 ppm region of the spectrum. The hydroxyl
protons for compound 3d, 3e, 3g, 3h, and 3i (Scheme 1)
appeared as a broad signal between 9.90 and 10.6 ppm. A sharp
singlet was observed in the 9.0−9.34 ppm region of the
spectrum, which corresponds to the azomethine proton. In the
1H NMR spectrum of compound 3e, methyl protons were
observed at δ 2.40 ppm as singlets. The sharp singlet at δ 9.02−
9.45 ppm was assigned to the azomethine (−CHN−) group.
The doublets at δ 6.95 (d, 2H, J = 8.50 Hz), 7.3 (d, 1H, J = 8.11
Hz), 7.75 (d, 1H, J = 8.45 Hz), and 7.95 (d, 2H, J = 8.55 Hz)
indicated the H12, H14, H5, H4, H11, and H15 protons
(Scheme 1), respectively. The signals observed as a singlet at δ
7.80 ppm may be assigned to proton H7. Aromatic protons of
compounds 3a, 3b, 3c, 3d, 3f, 3g, 3h, 3i ,and 3h showed similar
characteristics as those discussed in compound 3e. In the 13C
NMR spectrum of 3e, carbon atoms of the phenyl and
benzothiazole ring were observed at δ (116.63, 122.27, 122.36,
126.37, 128.34, 133.08, 134.36, 135.07, 149.92, 163.24, and
171.41) ppm values. A downfield shift in peak position was
observed at δ 166.49 ppm, and this should be due to the
presence of a carbon atom which is double bonded to nitrogen
atoms. The methyl carbon atom has been also observed at δ
21.54 ppm.
Figure 1. UV−vis spectrum of compound 3e: ···, pH = 1; , pH = 7;
---, pH = 13.
protonation values were carried out as follows: the sigmoid
curve of optical density or extinction coefficients at the
analytical wavelength (λ) was first obtained (Figure 1).
As shown in Figure 2a, the plot of pH versus the molar
extinction coefficient affords a sigmoidal curve. Calculations of
half-proton-gain values were carried out as follows: the sigmoid
curve of absorbance or extinction coefficients at the analytical
wavelength (A, λ) was first obtained (Figure 1). The
absorbance of the fully protonated molecule (Aca, absorbance
of conjugated acid) and the pure free base (Afb, absorbance of
free base) at an acidity were then calculated by linear
extrapolation of the arms of the curve. Equation 1 provides
the ionization ratio where the Aobs (the observed absorbance)
was in turn converted into molar extinction εobs using Beers law
of A = εbc (b = cell width, cm; c = concentration, mol.dm3)
(Aobs − Afb)
(εobs − εfb)
[HX]
[X]
I =
=
=
(Aca − Aobs
)
(ε − εobs)
(1)
ca
A linear plot of log I against pH, using the values −1.0 < log I <
1.0, had slope m, yielded the half-proton gain value as pH1/2 at
log I = 0. The pKa values were calculated by using eq 2.
B
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Figure 2. (a) pH-λ334 nm plot for compound 3e; (b) pH as a function of log I (334 nm) plot for the deprotonation of compound 3e.
Figure 3. . (a) FT-IR spectrum of compound 3e. (b) 2150−1650 cm−1 region FT-IR spectrum of compound 3e: , neutral media; ···, acidic media;
---, basic media.
Table 1. UV-vis Spectral Data and the Acidity Constants, pKa1 Values, of the Studied Compounds (3d−i)
spectral maximum λ/nm
acidity measurement
a
b
c
d
e
compound
neutral (log εmax
)
anion (log εmax
)
λ /nm
H1/2
corr.
3d
3e
3g
3h
3i
265 (3.25)
273 (3.17)
275 (3.21)
271 (3.15)
304 (3.40)
334 (3.49)
336 (3.28)
334 (3.31)
301
334
336
334
334
8.91 0.02
9.02 0.09
9.10 0.05
11.47 0.08
10.15 0.03
0.99
0.98
0.99
0.99
0.99
269 (3.20)
334 (3.31)
a
b
c
d
Measured in pH = 7 buffer solution. Measured in pH = 14 buffer solution. The analytical wavelength for pKa determination. Half-protonation
e
values uncertainties refer to the standard error. Correlation for log I as a function of pH graph.
pKa = m·pH1x/2
Possible mechanisms of deprotonation and protonation of
the novel benzothiazole Schiff Base are depicted in Schemes 2
(2)
As an example, pH1/2 was determined to be 9.10 for 3e, which
was the same value as the pKa1 of 3e determined using eq 3 The
m values are irrelevant in the studied pH regions for this
compound (Figure 3). Therefore, the half-protonation gain
values should give pKa1 by using eq 3 for the pH = 7−14
region.
and 3.
The studies on these subject showed that the pKa value of the
thiazole ring is 4.51.34,35 This value is very close to the values of
the protonation given in Table 3. The novel benzothiazole
Schiff bases 3a−j protonation and deprotonation process are
shown in Schemes 2 and 3. When considering the structures of
the novel benzothiazole Schiff bases 3a−j, it can be concluded
that they include two protonation sites. The protonation site is
either the aza nitrogen atom of the benzothiazole ring or the
imine nitrogen atom (Schemes 2 and 3).
pKa = pH1x/2
(3)
The acidity constants of the deprotonated and protonated
species calculated from their UV−vis spectra are given in
Tables 1 and 2.
Deprotonation (pKa1 values): When the novel benzothiazole
Schiff bases were ordered according to increasing acidity for the
deprotonation process, the following pattern was observed:
C
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Table 2. UV−vis Spectral Data and the Acidity Constants, pKa2 Values, of the Studied Compounds (3a−j)
spectral maximum λ/nm
acidity measurement
a
b
c
d
e
f
compound
neutral (log εmax
)
monocation (log εmax
)
λ /nm
H1/2
m
pKa2
corr
3a
3b
3c
3d
3e
3f
264 (3.16)
267 (3.40)
264 (3.24)
265 (3.25)
273 (3.17)
271 (3.31)
275 (3.21)
271 (3.15)
269 (3.20)
269 (3.21)
290 (3.40)
290 (3.33)
283 (3.26)
290 (3.17)
283 (3.38)
286 (3.35)
286 (3.27)
293 (3.30)
289 (3.36)
287 (3.30)
290
290
283
290
290
293
286
293
289
3.80 0.05
4.16 0.03
4.70 0.09
4.18 0.06
4.18 0.01
4.79 0.08
4.38 0.09
4.21 0.07
4.41 0.11
5.12 0.09
1.06
0.99
0.80
1.01
1.00
0.54
0.99
1.08
1.01
0.85
4.03
4.12
3.76
4.22
4.18
3.52
4.33
4.54
4.45
4.35
0.99
0.99
0.98
0.99
0.99
0.99
0.99
0.99
0.99
0.99
3g
3h
3i
3j
293
a
b
c
d
Measured in pH = 7 buffer solution. Measured in pH = 1 buffer solution. The analytical wavelength for pKa determination. Half-protonation
e
f
value uncertainties refer to the standard error. Slopes of log I-pH plot. Correlation for log I as a function of pH graph.
Scheme 2. Possible Deprotonation Patterns for Compounds
3e, 3g, and 3i
Table 3. Acidity Constants (pKa2) of the Experimental and
Calculated Values of the Synthesized 2-Amino Benzothiazole
Schiff Base Derivatives
calculated pKa
compound process
AM1
PM3
PM5
experimental pKa2
3a ⇌ 3a_pb
3b ⇌ 3b_pb
3c ⇌ 3c_pb
3d_dp ⇌ 3d
3d ⇌ 3d_pb
3e_dp ⇌ 3e
3e ⇌ 3e_pb
3f ⇌ 3f_pb
3g_dp ⇌ 3g
3g ⇌ 3g_pb
3h_dp ⇌ 3h
3h ⇌ 3h_pb
3i_dp ⇌ 3i
3i ⇌ 3i_pb
3j ⇌ 3j_pb
6.152
8.651
8.859
26.858
6.160
21.439
6.905
6.725
21.392
8.523
24.352
4.981
21.384
6.826
2.932
12.563
16.254
16.160
33.185
16.160
28.222
16.396
16.446
28.652
16.250
31.716
14.777
29.505
15.014
16.169
0.714
2.399
4.363
18.099
2.337
11.832
4.204
3.611
14.249
4.755
17.343
2.912
13.114
4.098
2.051
4.03
4.12
3.76
8.91
4.22
9.02
4.18
3.52
9.10
4.33
11.47
4.54
10.15
4.45
4.35
Scheme 3. Possible Protonation Patterns for Compounds 3e,
3g, and 3i
the anion dp-1 leads to anion dp-2. Because the resonance
effect of the −OH group at the para position of the phenyl ring
increases the electron density of the imine nitrogen, the
basicities of compounds 3e, 3g, and 3i also increase.
Protonation (pKa2 values): When the synthesized novel
benzothiazole Schiff bases were ordered according to increasing
acidity power for the first protonation, the following pattern
was observed:
As shown in Scheme 3, the protonation sites associated with
the second acidity constant of these benzothiazole Schiff bases
are the imine nitrogen (ap) and the aza-nitrogen of
benzothiazole ring (bp). The protonation changes and the
second acidity constant (pKa2) of 3a to 3j may be associated
with the protonation of the aza-nitrogen atom of the
benzothiazole ring. Because the m values in the log I acidity
graphs are known and are approximately 0.5−1.0, we can
predict that the protonation site is the aza-nitrogen of
benzothiazole ring (bp), which is the Hammett base.36,37
As shown in Scheme 2, compounds 3e, 3g, and 3i can
undergo possible deprotonation when exposed to basic media.
Under these conditions, the deprotonation may occur from the
OH group attached to the phenyl ring and rearrangement of
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Figure 4. H NMR spectra of (a) neutral, (b) protonated compound 3e.
Benzothiazole Schiff base derivatives which are electron
donating or electron withdrawing groups can affect the pKa
values. A comparison of these pKa values shows, as expected, an
increase or decrease in acidity when the functional groups are
changed. Because −CH3 substituents in the benzothiazole ring
of Schiff bases do not have mesomeric effects and they
inductively donate electrons to the ring, these −CH3
substituents cause a decrease in acidity. For compound 3g,
the −CH3 substituent in the benzothiazole ring is near the
nitrogen atom, and it is hypothesized that this substituent
comparatively decreased the acidity of compound 3g. On the
other hand, −OCH3 substituents attached to the phenyl ring
mesomerically donate electrons to the ring and inductively
withdraw electrons; thus, the acidity of this compound
comparatively increases. In addition, because the −OH
substituent at the para position of the phenyl ring increases
the electron density of the imine nitrogen atom, it also causes
the comparative acidity of the compound to decrease and its
basicity to increase. Owing to the substituent effect, when
comparing −OCH3 and −OH groups at the para position of
the phenyl ring on compounds 3c, 3e, 3f, and 3g, it has been
observed that the −OCH3 group increased the acidity of the
compound comparatively. It has also been confirmed that the
compounds 3c and 3f are the most acidic compared to the
other studied compounds. Other observed behavior is depend-
ent on the substituent effect and position, as demonstrated in
compound 3b, where there is a −CH3 group present at the para
position of the phenyl ring. In comparison to the −OCH3
groups at the para position of the phenyl ring in compounds 3c
and 3f, the −CH3 group was observed to decrease the acidity of
the compound comparatively.
1
In this study, FT-IR and H NMR spectroscopic measure-
ments of the target compounds were taken in order to define
the protonation sites. For example, in both acidic and basic
media, FT-IR and 1H NMR spectroscopic data for the
compound 3e, were compared with the original data. The
original FT-IR spectrum of the 3e compound is given in Figure
3.
As shown in Figure 3a, dislocations in FT-IR peaks facilitate
forcasting the protonation sites in the compound 3e. Also, FT-
IR spectroscopy was used to elucidate the effect of protonation
of the aza nitrogen of the benzothiazole ring. As seen in the FT-
IR spectrum in Figure 3b, no frequency change was observed in
the imine group of the compound 3e after we added 0.1 M HCl
(∼1 mL). Thus, it can be said that no protonation occurred at
the imine nitrogen according to these data. While stretching of
|
−NC− group in neutral form was observed at 1698 cm−1, it
shifted to 1684 cm−1 in acidic form. This decrease in frequency
should be due to the increase in dipole property of the nitrogen
|
atom, originating from the protonation at the −NC− group
in the benzothiazole ring.38 Therefore, as seen in Figure 3b, the
+
|
band at 1684 cm−1 indicates the existence of the H−NC−
structure in the benzothiazole ring.
Additionally, when the compound 3e in Figure 4 was
protonated, the protonation site was determined by evaluating
E
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the shifts in peak locations in the H NMR spectroscopic
measurements.
values of computed pKa values, which were obtained using the
computed themodynamic values of related physical properties
(Supporting Information, Tables S1, S2, and S3), with that of
the experimentally obtained pKa values.
We have compared the chemical shifts of the neutral species
3e with those of the protonated compounds. There is no
indication that protonation occurs on the imine nitrogen of
1
4. CONCLUSION
compound 3e. In the H NMR spectrum of compound 3e in
neutral media, the imine proton appears at 9.0 ppm as a sharp
singlet. The chemical shifts of the imino hydrogen in acidic
media (0.1 M HCl) (at 9.7 ppm 3e) indicate that the imine
nitrogen of the benzothiazole ring protonated. The position of
this signal is largely dependent on the nature of the substituents
on the benzothiazole ring. The seven aromatic protons of the
compound 3e appear as six doublets and a singlet. These
doublets observed at chemical shift values of 6.95 ppm to 7.95
ppm and at δ 7.80 ppm as a singlet. In acidic media, the
chemical shift of the aromatic protons is observed in the 7.2
ppm to 7.7 ppm region of the spectrum. As seen in Figure 5, a
Novel benzothiazole Schiff base compounds were synthesized,
and successfully targeted compounds were characterized.
Acidity constants values of the benzothiazole Schiff bases
were determined via both UV−vis spectroscopic method and in
the aqueous phase using semiempirical AM1, PM3, and PM5
methods. The calculated pKa values were compared with
experimental pKa values. The best correlation between the
experimental and theoretical pKa and acidity values of the
compounds was obtained using the PM5 calculation method.
Also, in the newly synthesized benzothiazole Schiff base,
protonation locations were determined both experimentally
and theoretically. The most stable form was the aza-nitrogen of
the benzothiazole ring (pb) for all of the compounds when
considering their relative stability at PM5.
The compounds 3c, 3f, and 3j were synthesized according to
the given references,39−41 but with several changes, for example,
in reaction time, solvent type, and atmospheric pressure. In
short, a decrease in reaction time resulted in an increase in the
reaction yield. Moreover, the solvent used in this study was less
dangerous to the environment compared to the solvents used
in the previous studies.
1
Consequently, UV−vis, FT-IR, and H NMR spectroscopic
measurements along with semiempirical calculations exhibited
that protonations of the benzothiazole Schiff base compounds
occur at the nitrogen atom in the thiazole ring. Studied
spectroscopic measurements and theoretical data are quite
compatible with each other. We believe the determined pKa
values of the targeted compounds in this study would
contribute to the development of the pharmaceutical industry.
Figure 5. A graph of acid dissociation constants, pKa, against PM5
aqueous phase computed acid dissociation constants, pKa, for bp
protonation for 3a−3j (3c, 3i, and 3j removed).
ASSOCIATED CONTENT
* Supporting Information
■
S
graph search for a correlation between experimental pKa values
and the PM5, which gives better correlation coefficient values,
calculated pKa values elucidates that there is a good parallelism
between the computed and experimental values.
Materials and solution, general procedure for the synthesis of
Schiff bases, synthesis, the theoretically (AM1, PM3 and PM5)
calculated values (pKa1 and pKa2) of the acidity constant, Tables
S1, S2 and S3. This material is available free of charge via the
Internet at http://pubs.acs.org.
The acidity affects different substituents attached to phenyl
ring of the benzothiazole Schiff base. Therefore, Figure 5 is
shown in two different series: pKa < 3.5 and pKa > 3.5.
According to the series pKa < 3.5 in Figure 5, methyl and
hydroxyl substituents have reduced the acidity constant. As
shown in series pKa > 3.5 in Figure 5, while the methoxy group
attached to the phenyl ring of benzothiazole Schiff bases
increased the acidity, the hydroxyl group reduced the acidity.
Therefore, it was found to be in compliance with the 3g and 3f
compounds. Regression values in series I and II have shown
that the calculated pKa value determined is in compliance with
the experimental pKa.
Table 3 lists the data theoretically obtained using the acidity
constant experimental values (pKa2). In this study, the
correlations were done by comparing the experimental and
theoretical calculations. We have determined that the best
correlated result utilized the PM5 method.
AUTHOR INFORMATION
Corresponding Author
*Tel.: +90 222 239 3750. Fax: +90 222 2393578. E-mail:
mujgan@ogu.edu.tr.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was financially supported by the ‘‘Theoretical and
experimental studies on several analogues of benzothiazole
Schiff bases that are drug precursors’’ research project at
Eskisȩ hir Osmangazi University, Eskisȩ hir (200419032). The
authors would like to thank Asst. Prof. Dr. Halil Berber at the
Department of Chemistry, for supplying the CACHE program
and BIBAM at Anadolu University. This work is dedicated to
The structures of studied compounds indicates that the 10
compounds, 3a−3j, have two proton centers. Close values of
acid dissociation constants, pKa, allow us to evaluate the
mechanism of proton gain process by comparing the absolute
̈
̆
the memory of our colleague, Prof. Dr. Cemil Ogretir, who died
on January 19, 2011. We would like to thank the editor and
anonymous reviewers for their review of the manuscript.
F
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synthesized Schiff bases and their QSPR study. Spectrochim. Acta, Part
A 2010, 75, 340−346.
(19) Ouf, A.; Ali, M. S.; Saad, E. M.; Mostafa, S. I. pH-metric and
spectroscopic properties of new 4-hydroxysalicylidene-2-aminopyrimi-
dine Schiff-base transition metal complexes. J. Mol. Struct. 2010, 973,
69−75.
(20) Poole, S. K.; Patel, S.; Dehring, K.; Workman, H.; Poole, C. F.
Determination of acid dissociation constants by capillary electro-
phoresis. J. Chromatogr. A 2004, 1037, 445−454.
(21) Ogretir, C.; Berber, H.; Asutay, O. Spectroscopic determination
of acid dissociation constants of some imidazole derivatives. J. Chem.
Eng. Data 2001, 46, 1540−1543.
(22) Ogretir, C.; Yarligan, S.; Demirayak, S. Spectroscopic
determination of acid dissociation constants of some biologically
active 6-phenyl-4,5-dihydro-3(2H)-pyridazinone derivatives. J. Chem.
Eng. Data 2002, 47, 1396−1400.
(23) Ogretir, C.; Dal, H.; Berber, H.; Taktak, F. F. Spectroscopic
determination of acid dissociation constants of some pyridyl Shiff
bases. J. Chem. Eng. Data 2006, 51, 46−50.
(24) Bhatt, V. K.; Jee, R. D. Micro-ionization acidity constants for
tetracyclines from fluorescence measurements. Anal. Chim. Acta 1985,
167, 233−240.
(25) Abbaspour, A.; Kamyabi, M. A.; Khalafi-Nezhad, A.; Rad, M. N.
S. Acidity constants and thermodynamic parameters of some phenol
derivatives in methanol plus water systems using potentiometry and
spectrophotometry methods. J. Chem. Eng. Data 2003, 48, 911−915.
(26) Moghimi, A.; Alizadeh, R.; Shokrollahi, A.; Aghabozorg, H.;
Shamsipur, M.; Shockravi, A. First anionic 1,10-phenanthroline-2,9-
dicarboxylate containing metal complex obtained from a novel 1:1
proton-transfer compound: Synthesis, characterization, crystal struc-
ture, and solution studies. Inorg. Chem. 2003, 42, 1616−1624.
(27) Albert, A.; Serjant, E. P. The Determination of Ionisation
Constants; Chapman and Hall Ltd.: London, U.K, 1984.
(28) Dewar, M. J.; Zoebish, E. G.; Healy, E. F.; Stewart, J. J. P.
Development and use of quantum mechanical molecular models. 76.
AM1: a new general purpose quantum mechanical molecular model. J.
Am. Chem. Soc. 1985, 107, 3902−3909.
REFERENCES
■
(1) Rana, A.; Siddiqui, N.; Khan, S. A. Benzothiazoles: A new profile
of biological activities. Ind. J. Pharm. Sci. 2007, 69, 10−17.
(2) Ban, M.; Taguchi, H.; Katsushima, T.; Takahashi, M.; Shinoda,
K.; Watanabe, A.; Tominaga, T. Novel antiallergic and antiinflamma-
tory agents. Part I: Synthesis and pharmacology of glycolic amide
derivatives. Bioorgan. Med. Chem. 1998, 6, 1069−1076.
(3) Yoshida, M.; Hayakawa, I.; Hayashi, N.; Agatsuma, T.; Oda, Y.;
Tanzawa, F.; Iwasaki, S.; Koyama, K.; Furukawa, H.; Kurakata, S.;
Sugano, Y. Synthesis and biological evaluation of benzothiazole
derivatives as potent antitumor agents. Bioorg. Med. Chem. Lett. 2005,
15, 3328−3332.
(4) Bradshaw, T. D.; Westwell, A. D. Curr. Med. Chem. 2004, 11,
1009−1021.
(5) Easmon, J.; Heinisch, G.; Hofmann, J.; Langer, T.; Grunicke, H.
H.; Fink, J.; Purstinger, G. Thiazolyl and benzothiazolyl hydrazones
̈
derived from α-(N)-acetylpyridines and diazines: Synthesis, anti-
proliferative activity, and CoMFA studies. Eur. J. Med. Chem. 1997, 32,
397−408.
(6) Westaway, S. M.; Thompson, M.; Rami, H. K.; Stemp, G.;
Trouw, L. S.; Mitchell, D. J.; Seal, J. T.; Medhurst, S. J.; Lappin, S. C.;
Biggs, J.; Wright, J.; Arpino, S.; Jerman, J. C.; Cryan, J. E.; Holland, V.;
Winborn, K. Y.; Coleman, T.; Stevens, A. J.; Davis, J. B.; Gunthorpe,
M. J. Design and synthesis of 6-phenylnicotinamide derivatives as
antagonists of TRPV1. Bioorg. Med. Chem. Lett. 2008, 18, 5609−5613.
(7) Sharma, V.; K. V, S. Synthesis and biological activity of some 3,5-
diaryl-1-benzothiazolopyrazoline derivatives: Reaction of chalcones
with 2-hyrazinobenzothiazoles. Eur. J. Chem. 2009, 6, 348−356.
(8) Iwan, A.; Gorecki, L.; Pociecha, D. Liquid crystalline properties of
new unsymmetrical compounds with benzothiazole core detected by
TG/DSC-POM-XRD. J. Therm. Anal. Calorim. 2012, 110, 43−49.
(9) Iwan, A.; Palewicz, M.; Krompiec, M.; Grucela-Zajac, M.; Schab-
Balcerzak, E.; Sikora, A. Synthesis, materials characterization and
opto(electrical) properties of unsymmetrical azomethines with
benzothiazole core. Spectrochim Acta A 2012, 97, 546−555.
(10) Iwan, A.; Siwy, M.; Janeczek, H.; Rannou, P. Synthesis and
mesomorphism of 2,5-bis(3,4-bis(n-alkoxy)phenyl)thiazolo[5,4-d]-
thiazole tetracatenar liquid crystals. Phase Transit 2012, 85, 297−308.
(11) Iwan, A.; Schab-Balcerzak, E.; Grucela-Zajac, M.; Skorka, L.
Structural characterization, absorption and photoluminescence study
of symmetrical azomethines with long aliphatic chains. J. Mol. Struct.
2014, 1058, 130−135.
(29) Stewart, J. J. P. Optimization of parameters for semiempirical
methods. 1. Method. J. Comput. Chem. 1989, 10, 209−220.
(30) Stewart, J. J. P. Optimization of parameters for semiempirical
methods. 2. Applications. J. Comput. Chem. 1989, 10, 221−264.
(31) Stewart, J. J. P. Mopac 2002. Fujitsu Limited: Tokyo, Japan,
1999.
(12) Iwan, A.; Bartosz, B.; Tazbir, I.; Sikora, A.; Schab-Balcerzak, E.;
Grucela-Zajac, M.; Skork, Ł. Structural and electrical properties of
mixture based on P3HT:PCBM and low band gap naphthalene
diimide-imines. Synth. Met. 2014, 189, 183−192.
(13) Sabaa, M. W.; Mohamed, R. R.; Oraby, E. H. Vanillin-Schiff’s
bases as organic thermal stabilizers and co-stabilizers for rigid
poly(vinyl chloride). Eur. Polym. J. 2009, 45, 3072−3080.
(14) Kaya, I.; Yildirim, M.; Avci, A. Synthesis and characterization of
fluorescent polyphenol species derived from methyl substituted
aminopyridine based Schiff bases: The effect of substituent position
on optical, electrical, electrochemical, and fluorescence properties.
Synth. Met. 2010, 160, 911−920.
(15) Ramakrishna, D.; Bhat, B. R.; Karvembu, R. Catalytic oxidation
of alcohols by nickel(II) Schiff base complexes containing
triphenylphosphine in ionic liquid: An attempt towards green
oxidation process. Catal. Commun. 2010, 11, 498−501.
(32) FCS Inc. CAChe WorkSystem Pro, V.; FCS Inc 15244 NW Ed.:
GreenbrierParkway: Beaverton, OR, 2004.
(33) Ogretir, C.; Gorgun, K.; Ozkutuk, M.; Sakarya, H. C.
Determination and evaluation of acid dissociation constants of some
novel benzothiazole Schiff bases and their reduced analogs by
spectroscopy. Arkivoc 2009, 197−209.
(34) Duran, M.; Canbaz, M. C. pKa Determination of newly
synthesized N-(benzothiazole-2-yl)-2-(4,5-dimethyl-1-(phenylamino)-
1H-imidazol-2-ylthio)acetamide derivatives. Ind. Eng. Chem. Res. 2013,
52, 8355−8360.
(35) Albert, A.; Goldacre, R.; Phillips, J. The strength of heterocylic
bases. J. Chem. Soc. 1948, 2240−2249.
(36) Hammett, L. P.; Deyrup, A. J. A series of simple basic indicators.
I. The acidity functions of mixtures of sulfuric and perchloric acids
with water. J. Am. Chem. Soc. 1932, 54, 2721−2739.
(37) Jorgenson, M. J.; Hartter, D. R. A critical re-evaluation of the
hammett acidity function at moderate and high acid concentrations of
sulfuric acid. New H0 values based solely on a set of primary aniline
indicators. J. Am. Chem. Soc. 1963, 85, 878−883.
(38) Sathyanarayanmoorthi, V.; Karunathan, R.; Kannappan, V.
Molecular modeling and spectroscopic studies of benzothiazole. J.
Chem. 2013, 2013, 1−14.
(39) Vicini, P.; Geronikaki, A.; Incerti, M.; Busonera, B.; Poni, G.;
Cabras, C. A.; La Colla, P. Synthesis and biological evaluation of
benzo[d]isothiazole, benzothiazole and thiazole Schiff bases. Bioorg.
Med. Chem. 2003, 11, 4785−4789.
(16) Soltani, N.; Behpour, M.; Ghoreishi, S. M.; Naeimi, H.
Corrosion inhibition of mild steel in hydrochloric acid solution by
some double Schiff bases. Corros. Sci. 2010, 52, 1351−1361.
(17) Alizadeh, K.; Ghiasvand, A. R.; Borzoei, M.; Zohrevand, S.;
Rezaei, B.; Hashemi, P.; Shamsipur, M.; Maddah, B.; Morsali, A.;
Akhbari, K.; Yavari, I. Experimental and computational study on the
aqueous acidity constants of some new aminobenzoic acid
compounds. J. Mol. Liq. 2009, 149, 60−65.
(18) Hemmateenejad, B.; Emami, L.; Sharghi, H. Multi-wavelength
spectrophotometric determination of acidity constant of some newly
G
DOI: 10.1021/je500679w
J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Journal of Chemical & Engineering Data
Article
(40) Billman, J. H.; Diesing, A. C. Reduction of Schiff bases with
sodium borohydride. J. Org. Chem. 1957, 22, 1068.
(41) Davion, Y.; Guillaumet, G.; Leger, J. M.; Jarry, C.; Lesur, B.;
Merour, J. Y. Synthesis of substituted 1,4-benzoxazepin-3-one
derivatives. Heterocycles 2004, 63, 1093−1112.
H
DOI: 10.1021/je500679w
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