Synthesis and characterization of cannabimimetic aminoalkylindole based 5-(4-alkyl-1-naphthoylamino)-1,3,4-thiadiazole-2-sulfonamides

Article abstract of DOI:10.1002/hc.20738

A novel series of cannabimimetic aminoalkylindole-based sulfonamide derivatives was synthesized. These new compounds were synthesized by reacting acyl chlorides of naphthoic acids with deacetylated acetazolamide in the presence of N-ethyl-morpholine to give structures incorporating 1-naphthoyl groups of cannabimimetic aminoalkylindoles and a five-membered heteroring typical of antiglaucoma sulfa drugs. The synthesized compounds were characterized using standard techniques. Photoluminescence of these derivatives was also studied, where more electron-donating groups on the aromatic ring at the para-position caused an increase in the intensity of the main peaks and shifts to higher emission wavelengths.

Full text of DOI:10.1002/hc.20738

Heteroatom Chemistry
Volume 22, Number 6, 2011
Synthesis and Characterization of
Cannabimimetic Aminoalkylindole Based
5-(4-Alkyl-1-naphthoylamino)-1,3,4-
Thiadiazole-2-Sulfonamides
Gulay Zengin,1 Zehra Nalbantbasi,2 Huseyin Zengin,1
and Hasan Turkmen3
1Department of Chemistry, Faculty of Science and Literature, Gaziantep University, Gaziantep,
27310, Turkey
2Department of Chemistry, Faculty of Science and Literature, Kahramanmaras Sutcu Imam
University, Kahramanmaras, 46100, Turkey
3Department of Chemistry, Faculty of Science and Literature, Harran University, Sanliurfa,
63300, Turkey
Received 25 March 2011; revised 24 May 2011
INTRODUCTION
ABSTRACT: A novel series of cannabimimetic
aminoalkylindole-based sulfonamide derivatives was
Cannabis sativa L. has long been used for medicinal
synthesized. These new compounds were synthe-
sized by reacting acyl chlorides of naphthoic acids
with deacetylated acetazolamide in the presence of
N-ethyl-morpholine to give structures incorporating
1-naphthoyl groups of cannabimimetic aminoalkylin-
doles and a five-membered heteroring typical of
antiglaucoma sulfa drugs. The synthesized com-
pounds were characterized using standard techniques.
and recreational purposes. ꢀ9-Tetrahydrocanna-
binol (ꢀ9-THC, Fig. 1) is the major psychoactive
component of marijuana and was first identified by
Gaoni and Mechoulam in 1964 [1]. Since the charac-
terization of THC many cannabinoids, that is, com-
pounds related to THC, and their metabolites have
been synthesized. The discovery of the cannabinoid
receptors CB1 [2], and CB2 receptors [3–5], has ad-
vanced the understanding of the manner in which
cannabinoids interact with biological systems.
Photoluminescence of these derivatives was also stud-
ied, where more electron-donating groups on the aro-
matic ring at the para-position caused an increase in
Cannabinoids exhibit a wide range of biological
properties, including analgesic, antiinflammatory,
the intensity of the main peaks and shifts to higher
ꢀ
C
emission wavelengths.
2011 Wiley Periodicals, Inc.
antiemetic, anticonvulsive, and anticancer proper-
ties. Studies into the action of cannabinoids have
strongly implicated the presence of a cannabinoid re-
ceptor located mainly in the central nervous system
(CNS) and several peripheral tissues, and is known
as the CB1 cannabinoid receptor [2]. This recep-
tor is the major target for psychoactivity; however,
the newly discovered ocular CB1 cannabinoid recep-
tor prompted research and development of novel
Heteroatom Chem 22:707–714, 2011; View this article on-
line at wileyonlinelibrary.com. DOI 10.1002/hc.20738
Correspondence to: G. Zengin; e-mail: gzengin@gantep.edu.tr.
2011 Wiley Periodicals, Inc.
c
ꢀ
707

708 Zengin et al.
FIGURE 2 Structure of acetazolamide (1).
(AAIs) as structure–activity relationships (SAR) [22].
They revealed that a 1-naphthoyl substituent pro-
vided potent CB1 cannabinoid activity. Now, as a re-
sult of work on cannabimimetic indoles lacking car-
bonyl groups, the naphthyl group with its lipophilic
and bulky character has been shown to interact
with the CB1 receptor primarily by aromatic stack-
ing [23,24]. Furthermore, a 1-naphthyl group of sul-
fonamide cannabinoids showed an increased affinity
for the CB2 receptor [20]. In addition, the heteror-
ing indole of AAIs has been replaced by the optimal
five-membered thiadiazole ring for potent CB2 affin-
ity [21]. Also, receptor docking and mutation stud-
ies identified a pharmacophore crucial for receptor-
ligand interaction by hydrogen bonding between the
carbonyl group of the cannabinoid ligand and a ly-
sine on transmembrane helix (TMH) 3 of the CB1
receptor [25,26].
As a consequence, the naphthyl group, thiadia-
zole function, and carbonyl group form structural
features in the design of the cannabinoids presented
herein. Whereas sulfonamides are known to have
antibacterial properties playing an important role
in chemotherapy [27,28], these new compounds
presented in this study may also have potential
as antimicrobials. These new cannabimimetic
FIGURE 1 Structure of ꢀ9-THC.
ophthalmic cannabinoid drugs to act specifically via
the cannabinoid receptors of the eye [6–8]. The sec-
ond cannabinoid receptor, the CB2 receptor, discov-
ered in 1993, is found to be associated with the im-
mune system, and is primarily located in the spleen,
tonsils, and immune cells [3–5].
Cannabinoid research extends out into modify-
ing the structure of cannabinoids, as well as in de-
veloping compounds structurally diverse from the
classical dibenzopyran structure. Recently, there has
been a burst of interest in the development of oph-
thalmic cannabinoid research with the discovery of
the ocular cannabinoid receptor in particular for
the treatment and management of glaucoma. Glau-
coma is an ophthalmic disorder characterized by
an increase in intraocular pressure (IOP), result-
ing in damage to the optic disk. It causes visual
disturbances and is one of the leading causes of
irreversible blindness. Although the use of sulfon-
amides as antiglaucoma agents has already been ini-
tiated [9–11], Kaur and coworkers have presented a
review of acetazolamides, members of the sulfon-
amide drug types, as topical glaucoma therapeu-
tics and offer promising areas for future investiga-
tion [12]. Kaur in earlier studies investigated various
ophthalmic preparations of acetazolamide [13]; the
structure of acetazolamide (1) is shown in Fig. 2. Re-
cently, several workers studied acetazolamide and its
analogues as chitinase inhibitors and presented an
interesting report on their SAR [14]. Other workers
developed numerous aroyl acetazolamide and sufon-
amide derivatives as carbonic anhydrase inhibitors,
where such were applied as potential gastric drugs
[15], tumor suppressants [16–18], and for the treat-
ment of glaucoma [19]. Ohta and coworkers studied
sulfonamide derivatives as new CB2 cannabinoid ag-
onists [20], and later imine derivatives based on five-
membered heterocycles as cannabinoids with anal-
gesic action [21].
AAI-based
5-(4-alkyl-1-naphthoylamino)-1,3,4-
thiadiazole-2-sulfonamides were characterized and
evaluated for antimicrobial properties. The results
of these investigations may offer further insight into
the treatment of glaucoma and reveal promising
impetus for antibiotic developments.
RESULTS AND DISCUSSION
Chemistry
In previous work, some 1-alkyl-3-(1-naphthoyl)
indoles were synthesized for cannabinoid activity
at the cannabinoid CB1 and CB2 receptors, where
1-naphthoyl groups were incorporated into these
structures [29]. Studies herein on the synthesis
of novel cannabimimetic AAI-based 5-(4-alkyl-1-
naphthoylamino)-1,3,4-thiadiazole-2-sulfonamides
are presented. 4-Methyl-1-naphthoic acid (2) is
commercially available, whereas 4-ethyl-, 4-propyl-,
The Winthrop group detailed the structural re-
quirements of cannabimimetic aminoalkylindoles
Heteroatom Chemistry DOI 10.1002/hc

5-(4-Alkyl-1-naphthoylamino)-1,3,4-Thiadiazole-2-Sulfonamides 709
SCHEME 1 Synthesis of 5-(4-alkyl-1-naphthoylamino)-1,3,4-thiadiazole-2-sulfonamides.
and 4-butyl- analogues of 4-alkyl-1-naphthoic acid
(3-5) were synthesized following the procedure
described in a previous paper [29]. Scheme 1 illus-
trates the synthesis of cannabimimetic AAI-based
5-(4-alkyl-1-naphthoylamino)-1,3,4-thiadiazole-2-
sulfonamides. Acetazolamide (1) was deacetylated
with concentrated hydrochloric acid to give 5-
amino-1,3,4-thiadiazole-2-sulfonamide (10) [30].
1-Naphthoic acids were converted to the acyl
chloride by refluxing with oxalyl chloride and sub-
sequent coupling with deacetylated acetazolamide
in the presence of N-ethyl-morpholine (NEM) gave
5-(4-alkyl-1-naphthoylamino)-1,3,4-thiadiazole-2-
sulfonamides 11–14.
tributed over sterilized petri dishes having a di-
ameter of 9 cm, (15 mL) after injecting cultures
(0.1 mL) of bacteria and yeast (105/mL for bacte-
ria and 104/mL for yeast), ensuring homogeneous
distribution of the food medium over the petri
dishes. Sterile filter paper disks (6 mm) injected
with 10 μL solutions in dichloromethane (80 μg/
disk) at a concentration of 8.0 mg/mL were placed
on the surface of the solid agar medium and were
slightly pressed. Petri dishes prepared as described
above were kept at 4◦C for 2 h to enable prediffu-
sion of the samples into the agar, and subsequently
samples inoculated with bacteria were incubated at
37 0.1◦C for 24 h and those with yeast were incu-
bated at 25◦C for 24 h. The inhibition zones formed
on the medium were measured and recorded in mm.
These studies were performed in triplicate. Strepto-
mycin was used as the standard antibiotic for the
evaluation of antimicrobial activity.
Determination of Antimicrobial Activity
The agar diffusion method using sterile filter paper
disks was used for the screening of antibacterial
and antifungal activities of synthesized 5-(4-alkyl-1-
naphthoylamino)-1,3,4-thiadiazole-2-sulfonamides
[31]. Inhibition zones formed on Mueller Hinton
Agar (MHA) and Sabourand Dextrose Agar (SDA)
(measured in mm) were evaluated. Experiments
were performed in triplicate, and the developing
inhibition zones were compared with those of
the reference parent compound, 5-amino-1,3,4-
thiadiazole-2-sulfonamide. The following collection
of microbes was used: three Gram-positive (Bacillus
cereus EU, Bacillus megaterium DSM 32, Enterococ-
cus faecalis A10), one Gram-negative (Escherichia
coli DM), and one yeast (Saccharomyces cere-
visiae). All microorganisms were provided by the
Microbiology Laboratory Culture Collection, the
Department of Biology, Kahramanmaras Sutcu
Imam University, Turkey.
Antimicrobial Studies
The test solutions were prepared in dichloro-
methane. The inhibition zones on the medium
were measured and recorded in mm. The results
of the antimicrobial activities are summarized in
Table 1.
The synthesized compounds were found to have
interesting antimicrobial activity inhibition zones
ranging in size from 12 to 32 mm. The antimicro-
bial activity observed for all synthesized compounds
and the standard streptomycin were in general
greater than the reference compound 5-amino-1,3,4-
thiadiazole-2-sulfonamide (10). Synthesized com-
pounds exhibited in general higher activity against
the Gram-positive bacteria than the Gram-negative
bacteria. Derivatives 13 and 14 both showed much
greater activity than the reference compound 10 and
the standard streptomycin. The reference precursor
compound10 revealed minimal antimicrobial activ-
ity against all bacteria. Streptomycin had greater
All the bacteria mentioned above were incu-
bated at 37
0.1◦C for 24 h by inoculation into
Nutrient Broth (Difco), and the yeast studied were
incubated at 25◦C in Sabouraud Dextrose Broth
(SDB) (Difco) for 24 h. MHA (Oxoid) and SDA ster-
ilized in a flask and cooled to 40–45◦C were dis-
Heteroatom Chemistry DOI 10.1002/hc

710 Zengin et al.
TABLE 1 Antimicrobial Activity Data and Selected Physicochemical Properties for 5-Amino-1,3,4-Thiadiazole-2-Sulfonamide
and 5-(4-Alkyl-1-naphthoylamino)-1,3,4-Thiadiazole-2-Sulfonamides
Microorganismc
B. megaterium E. fecalis
Physicochemical Properties
´3
´3
˚
Entitya,b
B. cereus
E. coli
MW
MV (A )
MR (A )
logP
˚
Streptomycind
14
10
–
12
30
32
17
10
–
14
20
24
15
8
–
–
16
28
9
12
–
–
14
20
NA
NA
NA
47.78
94.57
99.18
103.78
108.38
NA
10
11
12
13
14
222.24
348.39
362.42
376.45
390.47
571.79
880.20
890.36
989.30
996.75
0.44
1.82
2.22
2.62
3.01
aEntity refers to compounds.
bConcentration: 80 μg/ per disk.
cMicroorganism inhibition zone, mm; – denotes no activity; S. cereviciae (not shown here) was also used; however, all entities showed no
antifungal activity against S. Cerevisiae.
dStandard compound.
activity than derivatives 11 and 12. Only derivative
11 showed no activity against all bacteria whereas
derivative 12 only showed activity against Bacillus
cereus and Bacillus megaterium. In addition, no ac-
tivity was observed against the yeast (Saccharomyces
cerevisiae).
A comparison of the antibacterial activity of
the 5-(4-alkyl-1-naphthoylamino)-1,3,4-thiadiazole-
2-sulfonamides 11–14 revealed that the longer the
chain length of the 4-alkyl group, the greater the
activity; thus, activity decreased with decreasing
chain length. As the chain length decreases, activ-
ity is lost, primarily for Enterococcus faecalis and
Escherichia coli bacteria and lost completely for
the smallest molecule having a 4-methyl group. The
chain length plays a significant role in the antimicro-
bial activities of these 5-(4-alkyl-1-naphthoylamino)-
1,3,4-thiadiazole-2-sulfonamides.
to 5-(4-butyl-1-naphthoylamino)-1,3,4-thiadiazole-
2-sulfonamide. The antimicrobial activity for these
synthesized compounds showed a similar trend,
where antimicrobial activity was the lowest for
5-(4-methyl-1-naphthoylamino)-1,3,4-thiadiazole-2-
sulfonamide and the highest for 5-(4-butyl-1-naph-
thoylamino)-1,3,4-thiadiazole-2-sulfonamide. The
results showed there was a dependency between
biological activity and lipophilicity, where an-
timicrobial activity increased with increasing
lipophilicity. In addition, antimicrobial activity
increased with increasing MV, indicating that both
the 4-alkyl group and naphthoyl group appear to
play a dominating role on antimicrobial activity.
MR, as with lipophilicity, is also a molecular de-
scriptor used to relate chemical structure to observe
behavior. It can be seen from Table 1 that MR
increased with increasing lipophilicity, and, thus,
antimicrobial activity increased with increasing
MR.
The increasing chain length of the 4-alkyl group
of the synthesized compounds together with the
naphthoyl groups make these compounds highly
lipophilic, and therefore can greatly influence their
antimicrobial activity. In addition, all the synthe-
sized compounds possess carbonyl groups; thus,
possible hydrogen bonding with the active cell com-
ponents may be influential for the antimicrobial ac-
tivity, resulting in the interference and disruption of
normal cell processes.
Structure–Activity Relationships
Lipophilicity of compounds has an important effect
on their biological activity [32,33]. It is expressed
as logP, the octanol/water partition coefficient, and
high values indicate good permeation of compounds
through lipid layers of cell membranes. The predic-
tion of lipophilicity and other physicochemical prop-
erties such as molecular weight (MW), molecular
volume (MV), and molecular refractivity (MR) for
11–14 and the parent compound 10 was calculated
using HyperChem software in an attempt to corre-
late physicochemical properties of the compounds
with their antimicrobial activity [34]. The physico-
chemical properties MW, MV, MR, and logP of the
compounds are presented in Table 1.
Fluorescence Measurements
Absorption and photoluminescence spectra were
studied for 5-amino-1,3,4-thiadiazole-2-sulfonamide
Lipophilicity increased from 5-(4-methyl-
1-naphthoylamino)-1,3,4-thiadiazole-2-sulfonamide
(10)
and
5-(4-alkyl-1-naphthoylamino)-1,3,4-
(11–14) solutions,
thiadiazole-2-sulfonamide
Heteroatom Chemistry DOI 10.1002/hc

5-(4-Alkyl-1-naphthoylamino)-1,3,4-Thiadiazole-2-Sulfonamides 711
excited at 261 nm. The most striking feature was
that these compounds gave an intense emission
upon irradiation by UV light. The photolumines-
cence spectra of these compounds in CHCl3 are
shown in Fig. 3. Maximum luminescent intensity
was observed at 378 nm and the full width at half
maximum was 102 nm for compound 10. Com-
pound 10 exhibited a photoluminescence quantum
yield of 30% and a long excited-state lifetime of 2.84
ns. The photoluminescence intensity of peaks and
the quantum yields of the synthesized compounds
5-(4-alkyl-1-naphthoylamino)-1,3,4-thiadiazole-2-
sulfonamides (11–14) increased compared to that
of compound 10 due to the formation of larger
cyclic molecular structures. Also, the addition
of more electron-donating groups via the 4-alkyl
group onto ring at para-position of derivatives
caused an increase in intensity of main peaks and
shifted to the higher emission wavelengths. High
quantum yield is due to the extensive π-electron
delocalization in the large molecular structure.
Thus, it is evident that the fluorescence emission
intensity of the compound increases with more π
bonds in larger compounds or with the formation of
an electron-rich cyclic molecule. This electron-rich
cyclic molecule increases electron delocalization
and/or energy transfer from the excited state of
the 5-(4-alkyl-1-naphthoylamino)-1,3,4-thiadiazole-
2-sulfonamides, thus increasing the nonradiated
transition of the 5-(4-alkyl-1-naphthoylamino)-
1,3,4-thiadiazole-2-sulfonamides excited state, and
increasing the fluorescence emission.
The photoluminescence data for 5-amino-
1,3,4-thiadiazole-2-sulfonamide (10) and 5-(4-alkyl-
1-naphthoylamino)-1,3,4-thiadiazole-2-sulfonamides
11–14 are summarized in Table 2. The photolumi-
nescent properties of these compounds may indicate
great potential for numerous optical applications
and for medicinal biomarkers.
To conclude,
a
series of 5-(4-alkyl-1-
naphthoylamino)-1,3,4-thiadiazole-2-sulfonamides
was obtained where these structures combined the
1-naphthoyl groups of AAI with a five-membered
thiadiazole moiety typical of heterocyclic sulfon-
amide antiglaucoma agents. These new derivatives
prepared were tested for antimicrobial activity. It
was noted that the chain length and the naphthoyl
group of these 5-(4-alkyl-1-naphthoylamino)-
1,3,4-thiadiazole-2-sulfonamides appears to play
a dominating role on their antimicrobial activity.
Furthermore, these compounds possess carbonyl
functional groups, allowing for possible hydrogen
bonding with the active cell components, being
influential for antimicrobial activity, and resulting
in the interference and disruption of normal cell
processes. The fluorescence emission intensity
of the synthesized compounds increased with
the increasing π bonds as for larger compounds
or with the formation of an electron-rich cyclic
molecule.
FIGURE 3 Photoluminescence spectra of 5-amino-1,3,4-thiadiazole-2-sulfonamide (10) and 5-(4-alkyl-1-naphthoylamino)-
1,3,4-thiadiazole-2-sulfonamides 11-14 in CHCl3; samples were excited at 261 nm.
Heteroatom Chemistry DOI 10.1002/hc

712 Zengin et al.
TABLE 2 Photoluminescence Data for 5-(4-Alkyl-1-naphthoylamino)-1,3,4-Thiadiazole-2-Sulfonamides
Entity
λmaxEx (nm)
In Ex
λ
maxEm (nm)
In Em
φ (%)
f
τ (ns)
f
10
11
12
13
14
258 (221; 235; 291)
271 (220; 236; 254)
275 (220; 236; 255)
279 (222; 237; 255)
281 (225; 241; 259)
489
578
621
664
713
378 (352; 405)
484
572
614
656
704
30
35
37
39
41
2.84
3.26
3.45
3.64
3.84
403 (353; 381; 436)
406 (354; 381; 435)
408 (354; 385; 436)
411 (354; 384; 442)
λmax E x: maximum excitation wavelength; In Ex: maximum excitation intensity.
λmax E m: maximum emission wavelength; In Em: maximum emission intensity.
φf: quantum yield; τf : excited-state lifetime.
EXPERIMENTAL
General
photoluminescence quantum efficiencies of the
4-alkyl-1-naphthoylacetazolamide derivatives were
calculated using 9,10-diphenylanthracene as the
standard [35].
Commercially available and/or reagent grade sol-
vents and reagents purchased from Sigma-Aldrich,
Germany, or Merck, Germany were used with-
out purification unless otherwise stated. Column
chromatography was carried out using silica gel
(Merck, Kiesegel 60, 230-240 mesh). Analytical thin-
layer chromatography (tlc) was performed using
aluminum-coated Merck, Kieselgel 60 F254 plates.
All reactions were carried out under an atmo-
sphere of nitrogen gas. Reaction temperatures were
measured either externally, or by a thermometer in-
serted into the reaction mixture. Melting points were
recorded using an Electrothermal 9200 apparatus
and were determined using sealed capillaries and are
reported uncorrected. NMR spectra were recorded
on a Varian Mercury Plus 300 MHz, using CDCl3 as
the solvent. The NMR chemical shifts are presented
in parts per million (ppm), relative to the tetra-
methylsilane (TMS) (δ = 0), the internal standard.
The products obtained were investigated by GC–
MS (Agilent Technologies 6890N Network GC Sys-
tem coupled with Agilent Technologies 5975C VL
MSD MS). Elemental analyses for carbon, hydro-
gen, and nitrogen sulfur were performed using a
Thermo Scientific FLASH 2000 CHNS Organic El-
emental Analyzer.
5-(4-Methyl-1-naphthoylamino)-1,3,4-Thiadia-
zole-2-Sulfonamide (11). 5-(4-Methyl-1-naphthoy-
lamino)-1,3,4-thiadiazole-2-sulfonamide (11) was
prepared using the following typical procedure: To
a solution of 0.20 g (1.07 mmol) of 4-methyl-1-
naphthoic acid (2) in 5.0 mL of dichloromethane
at 0◦C, 0.45 mL (5.37 mmol) of oxalyl chloride
was added dropwise over 5 min. The resulting mix-
ture was allowed to warm to room temperature
and stirred for 1 h. The mixture was then heated
at reflux for 1 h. After cooling to room tempera-
ture, the solvent and excess oxalyl chloride were re-
moved by evaporation in vacuo to leave a residue.
The residue was dissolved in 6.0 mL of THF. The
resulting mixture was placed in an ice bath and
after chilling for several minutes a preprepared
mixture of 0.21 g (1.18 mmol) of 5-amino-1,3,4-
thiadiazole-2-sulfonamide (9) and 0.20 mL of NEM
(1.61 mmol) in 6.0 mL of THF was added drop-
wise. The resulting reaction mixture was allowed
to stir overnight at 0◦C. After warming to room
temperature, the white precipitate of NEM.HCl salt
was filtered out. THF was removed by evaporation
in vacuo to leave a residue. The residue was dissolved
in ethyl acetate. The organic extract was washed with
3 M hydrochloric acid and then saturated sodium bi-
carbonate solution and finally with brine. The extract
was dried (MgSO4) and concentrated by evaporation
in vacuo to give a residue. The crude product was
purified by column chromatography (hexane/diethyl
ether 9/1 v/v) to afford the product as a yellow solid,
yield: 70%; mp 41–42◦C; UV–vis (CH2Cl2) λmax: 207,
219, 240, 314 nm; IR (KBr): 3390, 3262, 2968, 2934,
1703, 1682, 1163, 1067, 849, 749 cm−1; 1H NMR
(300 MHz, CDCl3): δ 2.80 (s, 3H), 5.00 (s, 1H), 6.98 (s,
2H), 7.40 (d, J = 7.3 Hz, 1H), 7.53–7.61 (m, 2H), 8.20
(d, J = 8.3 Hz, 1H), 8.38 (d, J = 8.2 Hz, 1H), 9.20 (d,
FT-IR spectra were obtained using
a
PerkinElmer Spectrum 100 FT-IR Spectrome-
ter equipped with a Universal ATR Sampling
Accessory. The UV–vis spectra were recorded from
from 190 to 1100 nm on a PG Instruments Ltd T80
+ UV–vis Spectrometer. The single-photon fluo-
rescence spectra were collected on a PerkinElmer
LS55 luminescence spectrometer. All the sam-
ples were prepared in spectrophotometric grade
CHCl3 and analyzed in a 1 cm optical path quartz
cuvette. The solution concentration of the com-
pounds in CHCl3 was 1.0 × 10−5 mol L−1 and the
samples were excited at 261 nm wavelength. The
Heteroatom Chemistry DOI 10.1002/hc

5-(4-Alkyl-1-naphthoylamino)-1,3,4-Thiadiazole-2-Sulfonamides 713
J = 8.1 Hz, 1H); Anal. Calcd. for C14H12N4O3S2: C,
48.26; H, 3.47; N, 16.08; S, 18.41. Found: C, 48.38;
H, 3.51; N, 16.40; S, 18.55.
of Biology at Kahramanmaras Sutcu Imam Univer-
sity for his help in determining the biological activ-
ity. Also, the authors would like to thank the De-
partments of Chemistry at Gaziantep University and
Kahramanmaras Sutcu Imam University. We would
like to thank Prof. Mustafa Kucukislamoglu from
Sakarya University for the NMR spectral analysis.
5-(4-Ethyl-1-naphthoylamino)-1,3,4-Thiadiazole-
2-Sulfonamide (12). 4-Ethyl-1-naphthoic acid (3)
was used as the starting compound and the reaction
was carried out as described above. Yellow solid,
yield: 65%; mp 46-47◦C; UV–vis (CH2Cl2) λmax: 207,
219, 242, 316 nm; IR (KBr): 3360, 3200, 2958, 2924,
1723, 1683, 1122, 1067, 849, 749 cm−1; 1H NMR (300
MHz, CDCl3): δ 1.35–1.42, (t, J = 7.3, 3H), 3.20 (q,
J = 7.4 Hz, 2H), 5.00 (s, 1H), 7.00 (s, 2H), 7.41 (d,
J = 7.2 Hz, 1H), 7.60–7.71 (m, 2H), 8.25 (d, J = 8.2
Hz, 1H), 8.39 (d, J = 8.1 Hz, 1H), 9.22 (d, J = 8.1
Hz, 1H); Anal. Calcd. for C15H14N4O3S2: C, 49.71; H,
3.89; N, 15.46; S, 17.70. Found: C, 48.84; H, 3.92; N,
15.60; S, 17.81.
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(13).
4-Propyl-1-naphthoic
acid (4) was used as the starting compound and
the reaction was carried out as described above.
Yellow solid, yield: 65%; mp 80–81◦C; UV–vis
(CH2Cl2) λmax: 209, 219, 246, 320 nm; IR (KBr):
3360 (NH2), 3200, 2958, 2928, 1729, 1670, 1137,
1041, 849, 750 cm−1; H NMR (300 MHz, CDCl3): δ
1
1.20 (t, J = 7.2 Hz, 3H), 1.35–1.42 (m, 2H), 3.15 (t,
J = 7.4 Hz, 2H), 5.02 (s, 1H), 7.00 (s, 2H), 7.40 (d,
J = 7.1 Hz, 1H), 7.52–7.64 (m, 2H), 8.15 (d, J = 8.1
Hz, 1H), 8.30 (d, J = 8.2 Hz, 1H), 9.10 (d, J = 8.2
Hz, 1H); Anal. Calcd. for C16H16N4O3S2: C, 51.05; H,
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2-Sulfonamide (14). 4-Butyl-1-naphthoic acid (5)
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was carried out as described above. Yellow solid,
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1723, 1672, 1120, 1071, 848, 745 cm−1; 1H NMR (300
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ACKNOWLEDGMENTS
The authors wish to thank KSU for the financial sup-
port (KSU BAP 2008/2-5M). The authors are very
grateful to Prof. Metin Dıg˘rak from the Department
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