Fatty acids in heterocyclic synthesis part xii: Synthesis of surfactants from pyrazole, isoxazole, pyrimidine and triazine, incorporating the 1,3,4-thiadiazole moiety having dyeing and antimicrobial activities

Article abstract of DOI:10.1007/s11743-011-1301-4

The titled compounds were prepared from 2-amino-5-heptadecyl[1,3,4] thiadiazole (1). Diazotization of (1) produced (2) which was coupled with active methylene compounds and gave azo = hydrazono derivatives (3A, 3B) _a-d. It was found that there

Full text of DOI:10.1007/s11743-011-1301-4

J Surfact Deterg (2012) 15:179–190
DOI 10.1007/s11743-011-1301-4
ORIGINAL ARTICLE
Fatty Acids in Heterocyclic Synthesis
Part XII: Synthesis of Surfactants from Pyrazole, Isoxazole,
Pyrimidine and Triazine, Incorporating the 1,3,4-Thiadiazole
Moiety Having Dyeing and Antimicrobial Activities
•
Mahasen S. Amine Amal A. Mahmoud
•
•
Samy K. Badr Alaa S. Gouda
Received: 20 May 2011 / Accepted: 1 August 2011 / Published online: 20 September 2011
Ó AOCS 2011
Abstract The titled compounds were prepared from
2-amino-5-heptadecyl[1,3,4]thiadiazole (1). Diazotization
of (1) produced (2) which was coupled with active meth-
ylene compounds and gave azo ꢀ hydrazono derivatives
(3A, 3B)a–d. It was found that there is regio-specificity for
addition of different nucleophiles to these tautomers; thus,
nitrogen nucleophiles such as hydrazine hydrate, hydrox-
ylamine hydrochloride and thiourea were reacted via Azo
tautomer (3A) to yield pyrazole, isoxazole and pyrimidine
respectively (5-7), while carbon nucleophiles as phenyl-
isocyanate was reacted via the hydrazono tautomer (3B)
and produced triazine derivatives (4). Additionally, the
diazonium chloride (2) was coupled with alkaline 2-naph-
thol and produced 2-(5-heptadecyl-[1,3,4]thiadiazol-2-yl)
-1,2-dihydro-3-oxa-1,2-diaza-cyclopenta[a]naphthalene (8).
UV–visible spectra of the synthesized colored compounds
toxicity to human beings and the environment owing to
their high solubility and good biodegradability.
Keywords Dyes ꢀ Antiprotozoal ꢀ Antibacterial ꢀ Stearic
acid ꢀ 2-Aminothiadiazole ꢀ Pyrazol-ylazo-thiadiazole ꢀ
Azo-hydrazono tautomerism ꢀ Regiospecificity
Introduction
Five-membered, hetero-aromatic compounds containing
imine (–C=N–) groups, such as imidazole [1], thiazole [2],
triazole [3], oxadiazole [4], and thiadiazole [5–7] have long
been of interest as luminophores for optical application and
for dyeing, owing to their electron accepting nature [8].
1,3,4-Thiadiazoles were reported as being highly anti-
inflammatory [9], anti-microbial [10], pesticidal [11], as
having antiparasitic properties [12], and as being anticancer
[13] and anticonvulsant agents [14–16]. Additionally, it is
well known that some functionalized hydrazono deriva-
tives present trypanocidal activity [17, 18]. Compounds
containing 1,3,4-thiadiazole and hydrazone in one mole-
cule are framework to act the structure pattern of lead-
compound as a radical scavenger group [19–22].
(2-8) showed k
at 374–398 nm, while screening these
max
compounds in vitro against micro-organisms (including
structure-activity relationship SAR study) revealed high
antibacterial and moderate antifungal activities. Propoxy-
lation of compounds 1, 3, 5, 6, 7 and 8 with 3, 5, 7 mol of
propylene oxide produced nonionic surfactants I(a–c)–
IX(a–c) having surface active properties so, it is clear that
the tested surfactants can be used in the manufacture of
dyes, drugs, cosmetics, emulsifiers, pesticides, luminphores
for optical applications and many other industries with low
Chemistry
In continuation to our research program on the develop-
ment of new effective, cheap and safe biologically active
heterocyclic compounds having surface active properties
[23–30], herein we report the synthesis of pyrazole, isox-
azole, pyrimidine and triazine from a simple starting
material stearic acid. The versatile 2-amino-5-heptadecyl-
1,3,4-thiadiazole [28] (1) was prepared by refluxing stearic
M. S. Amine (&) ꢀ A. A. Mahmoud ꢀ S. K. Badr ꢀ A. S. Gouda
Department of Chemistry, Faculty of Science, Benha University,
P.O. 13518, Benha, Egypt
e-mail: d.ala85@yahoo.com
A. S. Gouda
e-mail: alaa.mohamed@fsc.bu.edu.eg
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Scheme 1 Synthesis of (5-
heptadecyl-[1,3,4]thiadiazol-2-
ylazo/hydrazono) derivatives
N
N
N
N
NaNO2/HCl/AcOH
0 -5 0C
N H 2
N
N C l
S
1
R
R
S
2
R=C 17H35
NaOAc
X
3
a
b
c
X
Y
H2
C
C2H5OH
CH3CO COOEt
CN COOEt
Y
0-5 0
C
N
N
N
N
COOEt COOEt
CH3CO CH3CO
X
X
N
N
d
C
Y
R
N
S
C H
R
N
H
S
Y
(3A)a-d
(3B)a-d
acid and thiosemicarbazide in boiling POCl3. Diazotization
of (1) with sodium nitrite and HCl/AcOH produced 5-hep-
tadecyl-[1,3,4]thiadiazole-2-diazonium chloride (2) which
was coupled smoothly with active methylene compounds as
ethyl acetoacetate, ethyl cyanoacetate, diethylmalonate and
acetylacetone via an electrophilic substitution reaction to
afford azo (3A) ꢀ hydrazono (3B) tautomers (3a–d) in a
good yield (Scheme 1). These compounds can be used in
dyeing and as an antiprotozoal agent [22].
N
N
N
N
COOEt
N
COCH3
N
H
N
C
R
N
S
R
S
- H+, + H+
C
H
COCH3
C
C
O
+
O
N
O
C
N
OC2H5
Ph
Ph
N
N
N
N
N
COCH3
O
N
COCH3
- EtOH
R
N
R
N
C
C
S
S
O
O
N
C
O
NH
Ph
Characteristic bands in IR spectra for 3a revealed two
carbonyl groups of the ester and ketone at 1742 and
1718 cm-1 respectively, for 3b strong absorption at
2264 cm-1 for mC:N. For 3c one strong band at 1742 cm-1
for two carbonyls of the ester, and for 3d one carbonyl of
the ketone at 1693 cm-1. For all compounds (3a-d) there
are weak and broad bands (3434–3277) cm-1 may be
attributed to mNH, mOH. Also, 13C-NMR shows a signal for
C=N of the hydrazono tautomer at 133 ppm and another
one at 85 ppm of the azo tautomer.
Ph
OC2H5
4
Scheme 2 Synthesis of 6-acetyl-2-(5-heptadecyl-[1,3,4]thiadiazol-
2-yl)-4-phenyl-2H-[1,2,4] triazine-3,5-dione
reacted via the azo tautomer (3Aa) to produce 4-(5-heptade-
cyl-[1,3,4]thiadiazol-2-ylazo)-5-methyl-2H-pyrazol-3-ol (5),
4-(5-heptadecyl-[1,3,4]thiadiazol-2-ylazo)-3-methyl-iso-
xazol-5-ol (6), and 5-(5-heptadecyl-[1,3,4]thiadiazol-
2-ylazo)-2-mercapto-6-methyl-pyrimidin-4-ol (7) respec-
tively (Schemes 3 and 4). (These compounds containing the
azo function can be utilized as dyeing materials). The mech-
anisms are as follows:
The mass spectrum of (3a–d) also proved this tautom-
X
?
erism, which showed [M -azo group (
(
)]
)],
N
N
CH
Y
X
?
and [M -imino group (
The IR spectrum of pyrazole (5) showed three bands at
3300, 3220 and 3120 cm-1 attributable to OH ꢀ NH (tau-
tomeric form), the mass spectrum showed (M?-H2O at 430,
1.3%), IR spectra for isoxazole (6) showed mOH at 3325 cm-1
(
)]
)] for all the prepared
N
C
Y
compounds (3a–d).
,
It was found that the electrophilic reagent reacted regio-
specifically with these tautomers thus, phenylisocyanate was
reacted via the hydrazone tautomer 3Ba to produce the highly
substituted triazine, 6-acetyl-2-(5-heptadecyl-[1,3,4]thia-
diazol-2-yl)-4-phenyl-2H-[1,2,4]-triazine-3,5-dione (4). The
13C-NMR showed d ppm at 100.5, 155.5, 158.9 for the 3C of
isoxazole ring. The mass spectrum showed (M?= 449, 0.9).
The IR spectrum of pyrimidine (7) showed mOH, NH ‘s at 3380,
3277 and 3176 cm-1, mC=S at 1080 cm-1 and denoted a car-
bonyl group. 13C NMR showed d ppm at 183.1 for C–OH,
180.4 for C=S. The mass spectrum showed a molecular ion
peak at (M? = 492, 4.4%). Coupling the diazonium salt (2)
with an alkaline solution of 2-naphthol produced 2-(5-hepta-
decyl- [1,3,4]thiadiazol-2-yl)-1,2-dihydro-3-oxa-1,2-diaza-
cyclopenta[a]naphthalene (8).
IR spectrum showed a sharp band for mC=O’S at 1705 cm-1
,
and 13C-NMR showed d ppm at 143.8, 155.6 for cyclic
(2C=O) and 198.5 for ketonic (C=O) besides the other signals
of aliphatic and aromatic carbon. Mass spectrum (M?-
2 = 551, 4.6%) and M?-triazine moiety m/z = 324, 5.2%).
The mechanism of the reaction is as follows (Scheme 2).
Nucleophilic reagents were reacted regiospecifically
with the azo tautomer, thus nitrogen nucleophiles such as
hydrazine, hydroxylamine hydrochloride and thiourea were
The IR spectra of compound (8) showed mNH at
3228 cm-1, the mass spectrum showed (M? at 494, 0.5%)
(Scheme 5).
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J Surfact Deterg (2012) 15:179–190
181
N
N
Scheme 3 Synthesis of 4-(5-
heptadecyl-[1,3,4]thiadiazol-
2-ylazo)-5-methyl-2H-pyrazol-
3-ol, and 4-(5-heptadecyl-
[1,3,4]thiadiazol-2-ylazo)-
3-methyl-isoxazol-5-ol
N
N
COOEt
+
NH2-XH
COOEt
N
N
O
CH
R
N
CH
S
R
N
S
C
X
C
O
H3C
N
H2
CH3
R = C17H35
-H2O
- H,+ H
N
N
N
N
O
C
OH
- C2H5OH
- H,+ H
OC2H5
XH
N
N
N
R
X
S
N
CH
R
S
C
H3C
N
N
H3C
5, 6
5; x= NH
6; x= O
O
N
N
N
N
C
OEt
H2N
COOEt
N
N
O
HC
R
N
S
CH
R
N
S
C
O
+
C
S
C
S
N
H 2
CH3
H3C
N
C
NH
S
H2N
O
C
N
N
N
O
-H + ,+H +
OEt
-H2O
N
C
OEt
N
CH
R
N
H2N
C
CH
R
N
S
NH
C
2
S
N
HO
C
C
S
H
N
CH3
H3C
- C2H5OH
N
N
N
N
OH
OH
N
N
R
NH
R
S
N
N
S
N
H3C
H3C
N
SH
N
S
7
Scheme 4 Synthesis of 5-(5-heptadecyl-[1,3,4]thiadiazol-2-ylazo)-2-mercapto-6-methyl-pyrimidin-4-ol
Electronic Absorption Spectra
absorption value. The second band observed within
wavelength range 290–310 nm, is attributed to the excita-
tion of p electron within the –N=N– and that –C=N– bonds
of 1,3,4-thiadiazole moiety of the molecule [31, 32].
The third band was mostly observed within the visible
range 374–398 nm, this band may be assigned to electronic
transition arising from charged transfer (CT) originating
from the electron rich –N=N– group toward the electron
poor heterocyclic thiadiazole moiety, i.e. due to the tran-
sition within the whole molecule (intramolecular charge
transfer).
Non-conjugated 1,3,4-thiadiazole had no selective absorp-
tion above 220 nm, but conjugated substituted 2-amino-
1,3,4-thiadiazole with lone pair caused bathochromic
shifts. Band assignment of the absorption spectra of the
prepared compounds were investigated by recording their
spectra in chloroform at 25 °C (cf. Table 1; Fig. 1).
The first absorption was observed within wavelength
range 248–264 nm, it may be assigned to local p ? p*
electronic transition and it was characterized by high
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N
N
.
n P.O
I(a-c)
IX(a-c)
R
NH2
S
1
i
N
N
N
N
N
N
- H+, + H+
vii
R
N
NH
S
R
S
N
N
N
N
Cl
R
S
O
3
a
b
c
X
Y
HO
2
X
Y
CH3CO COOEt
CN COOEt
H2C
ii
8
COOEt COOEt
CH3CO CH3CO
N
N
II(a-c) n P.O.
III(a-c)
N
N
d
X
C
N
X
CH
N
R
N
IV(a-c)
S
R
N
N
H
S
Y
V(a-c)
Y
(3 A)a-d
(3 B)a-d
N
N
N
COOEt
COOEt
CH
COCH3
N
N
C
R
N
H
S
R
N
S
COCH3
3a B
R = C17H35
3a A
v
iv
vi
iii
N
N
OH
O
N
N
OH
N
N
R
N
S
N
R
NH
S
N
H3C
N
H3C
N
N
O
6
N
N
OH
5
N
N
VII(a-c)
COCH3
O
R
N
N
VI(a-c)
S
R
NH n P.O.
S
S
N
VIII(a-c)
H3C
N
7
Ph
4
Scheme 5 Synthetic routes of non-condensed thiadiazoles. Condi-
tions: (i) NaNO2/HCl, stirring at 0–5 °C 2 h (ii) EtOH, AcONa,
stirring at rt for 12 h (iii) PhNCO, dioxane, Et3N, reflux 5 h (iv)
N2H4.H2O, dioxane, reflux 6 h; (v) NH2OH.HCl, dioxane, AcONa,
reflux for 6 h (vi) (NH2)2CS, EtONa, EtOH, reflux 7 h (vii)
2-naphthol in 10% NaOH solution, stirring at 0–5 °C for 0.5 h
Biological Activity1
Some of the synthesized compounds were screened in vitro
against some bacteria, namely Escherichia coli and
Staphylococcus aureus, and some fungi, namely Aspergil-
lus flavus and Candida albicans. Tetracycline and
Amphotericin B were taken as positive references for
antibacterial and antifungal agents respectively.
Table 1 kmax values for synthesized compounds
Compound
k1 (nm)
k2 (nm)
k3 (nm)
1
3
4
5
6
7
8
252
256
264
252
248
254
248
–
310
306
306
306
306
290
–
376
374
376
378
376
398
The results are tabulated in Table 2, which shows that
the samples have high antibacterial and moderate anti-
fungal activities on the tested micro-organisms.
1
Antibacterial and antifungal activity was investigated at the Micro
Analytical Center, Faculty of Science, Cairo University using
a modified Kirby–Bauer disc diffusion method [33, 34]
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183
2.5
(1)
(3)
(4)
(5)
(6)
(7)
(8)
2.0
1.5
1.0
0.5
0.0
250
300
350
400
450
500
550
Wavelength, nm
Fig. 1 UV–Vis absorption spectra of some synthesized compounds
(1 9 10-5 M) in CHCl3 at 25 °C
Structure-Activity Relationship (SAR) of Some
Synthesized Thiadiazole Derivatives
As a part of our study on the effect of the synthesized thia-
diazole derivatives on the microorganisms (bacteria & fungi),
a structure-activity relationships (SAR) study was performed.
Herein, we focused on the effect of a certain substituent
on the biological activity of the 2-aminothiadiazole (1).
Also, the effect of construction of other heterocyclic ring
condensed to the thiadiazole ring on the biological activity
was also studied. Two bacteria strains [Escherichia coli
(Gram-negative) & Staphylococcus aureus (Gram-posi-
tive)] and two fungi strains (Aspergillus flavus and Can-
dida albicans) were selected to study these effects.
Introduction of a diazo group into the starting material
has only a slight effect on the antibacterial activity (com-
pound 3a).
Introduction of a non-condensed triazine ring (in com-
pound 4) in the thiadiazole diminished activity against both
bacterial strains and showed a good activity against Asper-
gillus flavus. Furthermore, addition of a pyrazole or isoxazole
ring in a non-condensed way to thiadiazole (compounds 5 and
6) demonstrated excellent antibacterial activity. Isoxazole
derivatives (compound 6) exhibited only moderate antifungal
activity against Candida albicans.
Thiadiazolylpyrimidine (compound 7) showed antibac-
terial and antifungal activities similar to the aminothi-
adiazole derivative (compound 1).
Nonionic Surfactants from Some Synthesized
Heterocyclic Compounds
The built up surfactant molecules contain heterocyclic
thiadiazole are most important class of surface active
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J Surfact Deterg (2012) 15:179–190
agents containing a heterocyclic moiety due to their dual
characteristics, one due to conflict between the affinity of
the hydrophobic and hydrophilic structure shows surface
active properties and a second one that is due to the het-
erocyclic moiety confirmed with aid of a hydrophilic
moiety (propylene oxide) give biological activity.
easily. The biodegradation of these compounds depends
mainly on the propylene oxide chain length due to the same
hydrophobic part. The results showed that in the first day
40–50% of the surfactants was biodegradable, after that
they later decreased until the 6th day by which time they
had disappeared. It means that these compounds are safe
for human beings as well as the environment.
Propoxylation of some of the new compounds (1, 3(a–d)
,
5, 6, 7, and 8) with various quantities of propylene oxide
(3, 5, and 7 mol) produced nonionic surfactants I(a–c)–
IX(a–c), the structure of which was confirmed via IR [35]
Experimental Protocols
1
and H-NMR spectra. IR-spectra showed a broad band in
the region of (3500–2500) cm-1 (mOH) and two other bands
in the regions (1100–1000) and (950–900) cm-1 for (mC–
O–C ether linkage of the polypropoxy chain) besides the
original bands of these compounds.1H-NMR spectra
showed the protons of the propyleneoxy groups which
appear as broad multiple signals in the region of (3.2–3.7)
ppm in addition to other signals of these compounds.
The surface active properties of the prepared propoxy-
lated compounds I(a–c)–IX(a–c) were measured in a
neutral medium by traditional procedures to evaluate the
possible utilization of these compounds in various indus-
trial fields.
The structural assignments of new compounds are based on
1
their elemental analysis and spectral data (IR, H NMR,
13C NMR, Mass spectra).
All melting points are uncorrected and were determined
by the open capillary method using a Gallen Kamp melting
point apparatus.
IR-Spectra (KBr disk) of the synthesized compounds
were recorded on FT/IR-BRUKER, Vector 22 (Germany),
JASCO FT/IR-4100 (Japan), and JASCO FT/IR-
1
460?(Japan) instruments. H- and 13C-NMR spectra were
recorded in deuterated chloroform (CDCl3) or dimethyl-
sulfoxide (DMSO-d6) as a solvent on a Varian Mercury
VXR-300 spectrometer (300 MHz for 1H NMR and
75 MHz for 13C NMR) using TMS as internal reference
and chemical shifts are expressed in d(ppm). The mass
spectra were recorded on a Shimadzu GCMS-QP-1000EX
mass spectrophotometer at 70 eV. The electronic absorp-
tion spectra were recorded on a UV/Vis spectrophotometer,
JASCO, Model V-350 (Japan), 200–900 nm.
The surface and interfacial tension were determined
according to Findly [36]. The resulting data in (Table 3)
show that the surface and interfacial tensions increased
upon increasing the number of propylene oxide units added
to the molecule [37]. All these compounds show high cloud
points, when in hot water, which increased with an
increasing number of moles of propylene oxide [38].
Also, the synthesized compounds exhibited efficient
wetting properties—wetting time decreased with an
increasing number of propylene oxide units. Emulsion
stability decreased with an increasing number of propylene
oxide units [39], while the foam height increases [40].
Thus, the surface active properties were independent of
heterocyclic thiadiazole but dependent on the hydrophobic
(C18) and hydrophilic (propylene oxide units) properties,
however, heterocyclic thiadiazole revealed biological
activities of the synthesized molecules, i.e., these com-
pounds are used as effective emulsifying agents in many
fields, such as cosmetics, formulations, pesticides, dyes,
textiles, etc.
Homogeneity of all compounds synthesized was
checked by TLC. All the synthesized compounds gave
satisfactory elemental analyses. Surface active properties
were carried out at the Chemistry Department, Faculty of
Science, at Benha University, Egypt.
Synthesis of 2-Amino-5-heptadecyl-[1,3,4]thiadiazole
(1)
It was prepared according to our procedure reported in Ref.
[28].
General Procedure for Synthesis of (5-Heptadecyl-
[1,3,4]thiadiazol-2-ylazo/Hydrazono) Derivatives (3a-d)
Biodegradability of the Synthesized Surfactants
To evaluate how environmentally friendly the compounds
are, the biodegradability of the synthesized compounds was
evaluated, determined by a die-away test, followed by
surface tension measurements [41]. The biodegradability
data are given in (Table 4), within the experimental accu-
racy, all the prepared nonionic surfactants seem to degrade
A solution of 1 (0.01 mol) in concentrated hydrochloric
acid (20 mL) and (10 mL) water was treated with a cold
saturated solution of sodium nitrite (0.7 gm) for 1 h with
o
stirring and cooling at 0–5 C for 2 h. The clear diazonium
salt solution (2) was then added dropwise to a solution of
ethyl acetoacetate, ethyl cyanoacetate, diethylmalonate and
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185
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J Surfact Deterg (2012) 15:179–190
Table 4 Biodegradability of the synthesized surfactants
Compd.
No of moles
1st day
2nd day
3rd day
4th day
5th day
6th day
7th day
I(a–c)
3
5
7
3
5
7
3
5
7
3
5
7
3
5
7
3
5
7
3
5
7
3
5
7
3
5
7
53
48
45
51
46
41
48
45
41
52
49
44
60
57
54
55
53
50
46
43
41
50
46
41
63
55
47
66
60
50
60
54
52
57
51
52
68
62
55
69
64
61
67
62
60
57
51
50
60
54
52
67
64
58
75
68
62
77
68
65
67
58
56
74
66
57
77
76
73
78
69
66
67
85
56
77
68
65
75
69
66
85
78
74
84
71
67
75
69
67
83
78
66
85
81
79
86
85
82
75
69
67
84
71
67
84
80
77
95
91
83
91
84
79
82
76
72
97
84
75
90
88
90
94
92
90
82
77
72
94
84
80
92
88
45
–
–
–
–
–
–
–
93
–
II(a–c)
91
88
86
84
83
–
III(a–c)
IV(a–c)
V (a–c)
VI(a–c)
VII(a–c)
VIII(a–c)
IX(a–c)
–
–
90
–
90
87
96
–
–
–
–
–
–
–
–
–
–
–
–
–
88
84
85
–
–
–
90
–
91
89
–
–
–
–
92
92
–
–
acetylacetone (0.01 mol) in ethanol (50 mL) containing
sodium acetate (1 gm) at 0–5 °C. The pH of the coupling
mixture, in each case, was maintained at 5–6 through the
coupling process by adding sodium acetate. After the
complete addition of the diazonium salt, the reaction
mixture was stirred at room temperature over night. The
precipitated products separated upon dilution with cold
water (50 mL) and they were filtered off, washed with
water several times, dried and recrystallized from ethanol.
Compound 3a was obtained as yellowish brown powder
in 77% yield, M.P. 80–82 °C; IR(KBr) m (cm-1): 3434
(NH), 2985, 2938 (aliphatic CH stretching), 1742, 1718
206, 177 (2C=O), 168, 173 (2C=N), 133.3 (C=N hydrazono
tautomer), 85.6 (–CH–N=N azo tautomer), 61 (CH2 ethoxy),
14.1 (CH3 ethoxy), 25.2 (CH3C=O), beside sp3 carbons of
aliphatic side chain 14.1 (terminal CH3), 22.7, 28.5, 29.3(2C),
29.6 (10C), 30.9, 31.9; MS m/z [% rel.int.]: 482 (M? ?2,
2.86), 353(16.84), 312(13.37), 115(63.37), 57(100). Anal.
Calcd. (%) for C22H38N4SO: C; 64.98, H; 9.42, N; 13.78, S;
7.89. Found: C; 64.86, H; 9.23, N; 13.64, S; 7.60.
Compound 3b was obtained as pale yellow crystals in
64% yield, M.P. 95–97 °C; IR(KBr) m (cm-1): 3277 (NH),
2984, 2938 (aliphatic CH stretching), 2264 (C : N), 1746
(C=O), and 1516 (C=N stretching); 1H-NMR spectrum
(CDCl3) showed signals at d; 5.2 (s,H,NH) which disap-
peared on addition of D2O, 3.5 (q, 2H, CH2 ethoxy), 3.1
(t, 3H, CH3 ethoxy), 1.2–1.6 (m, 32H, 16CH2 of alkyl
chain), 0.9 (t, 3H, terminal CH3), MS m/z [% rel.int.]: 464
(M? ?1, 3.60), 268(9.10), 312(13.37), 115(84.80), 57(100).
Anal. Calcd. (%) for C24H41N5O2S: C; 62.17, H; 8.91, N;
15.10, S; 6.92. Found: C; 62.34, H; 9.03, N; 15.35, S; 7.04.
1
(2C=O), and 1647 (C=N stretching); H-NMR spectrum
(DMSO-d6) showed signals at d; 4.7 (s,H,NH) which dis-
appeared on addition of D2O, 3.8 (q, 2H, CH2 ethoxy), 3.2
(t, 3H, CH3 ethoxy), 2.9 (s, 3H, CH3C=O), 1.2–1.6 (m,
32H, 16CH2 of alkyl chain), 0.9 (t, 3H, terminal CH3, 2.9
(s, 2H, CH2CN), 1.6–1.2 (m, 32H, 16CH2 of alkyl chain),
0.9 (t, 3H, terminal CH3); 13C NMR (DMSO-d6) d (ppm):
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J Surfact Deterg (2012) 15:179–190
187
Compound 3c was obtained as yellow powder in 71%
yield, M.P. 70–72 °C; IR(KBr) m (cm-1): 3261 (NH), 2985,
2938 (aliphatic CH stretching), 1742 (2C=O sharp), and
1626 (C=N stretching); the 1H-NMR spectrum (DMSO-d6 )
showed signals at d; 4.3 (s,H,NH) which disappeared on
addition of D2O, 3.3 (q, 4H, 2CH2 ethoxy), 3.1 (t, 6H,
2CH3 ethoxy), 1.2–1.6 (m, 32H, 16CH2 of alkyl chain), 0.9
(t, 3H, terminal CH3), MS m/z [% rel.int.]: 508 (M? -2,
0.05), 311(26.98), 128(45.68), 115(100). Anal. Calcd. (%)
for C26H46N4O4S: C; 61.14, H; 9.08, N; 10.97, S; 6.28.
Found: C; 61.22, H; 9.23, N; 10.66, S; 6.45.
Synthesis of 4-(5-Heptadecyl-[1,3,4]thiadiazol-2-ylazo)-
5-methyl-2H-pyrazol-3-ol (5)
Equimolar amounts (0.005 mol) of 3a and hydrazine
hydrate in 30 mL of 1,4-dioxane were heated under reflux
for 6 h. The reaction mixture was concentrated and then
triturated with ethanol. The solid produced was filtered off,
dried and recrystallized from ethanol. Compound 5 was
obtained as dark green crystals in 70% yield, M.P.
101–103 °C; IR(KBr) m (cm-1): 3300 (OH), 3220–3120
(NH), 2920, 2850 (aliphatic CH stretching), 1663 (C=N
stretching); the 1H-NMR spectrum (DMSO-d6) showed
signals at d; 6.99 (s, 1H, OH) which disappeared on
addition of D2O, 4.7 (s,H,NH) which disappeared on
addition of D2O, 2.8 (s, 3H, CH3-C=N), 1.2–1.6 (m, 32H,
16CH2 of alkyl chain), 0.88 (t, 3H, CH3); 13C NMR
(DMSO-d6) d (ppm):) 177, 168, 142 (3C=N), 164 (C–OH),
101.4 (= C–N=N– of pyrazole ring), 12.2 (CH3C=N),
beside sp3 carbons of aliphatic side chain 14.1 (terminal
CH3), 22.7, 28.5, 29.3(2C), 29.6 (10C), 30.9, 31.9; MS m/
z [% rel.int.]: 430 (M? -H2O, 1.3), 323 (19.3), 295 (92.4),
134 (100). Anal. Calcd. (%) for C23H40N6OS: C; 61.57, H;
8.99, N; 18.73, S; 7.15. Found: C; 61.68, H; 8.91, N; 18.88,
S; 7.23.
Compound 3d was obtained as brownish yellow crystals
in 69% yield, M.P. 82–84 °C; IR(KBr) m (cm-1): 3177
(NH), 2919, 2850 (aliphatic CH stretching), 1693 (2C=O
1
sharp), and 1577 (C=N stretching); the H-NMR spectrum
(CDCl3) showed signals at d; 4.9 (s,H,NH) which disap-
peared on addition of D2O, 2.9 (s, 6H, 2CH3C=O), 1.2–1.6
(m, 32H, 16CH2 of alkyl chain), 0.9 (t, 3H, terminal CH3),
MS m/z [% rel.int.]: 450 (M?, 0.04), 134(24.63),
115(46.67), 88(100). Anal. Calcd. (%) for C24H42N4O2S:
C; 63.96, H; 9.39, N; 12.43, S; 7.11. Found: C; 64.07, H;
9.33, N; 12.55, S; 7.23.
Synthesis of 6-Acetyl-2-(5-heptadecyl-[1,3,4]thiadiazol-
2-yl)-4-phenyl-2H-[1,2,4]triazine-3,5-dione (4)
Synthesis of 4-(5-Heptadecyl-[1,3,4]thiadiazol-2-ylazo)-
3-methyl-isoxazol-5-ol (6)
To a mixture of equimolar amounts (0.01 mol) 3a and
phenyl isocyanate in 30 mL of 1,4-dioxane, a catalytic
amount of triethylamine (0.5 mL) was added. The reaction
mixture was heated under reflux for 5 h, concentrated,
cooled at room temperature, poured onto cold water
(50 mL) and neutralized with diluted HCl. The solid
product that formed was collected by filtration, dried and
recrystallized from 1,4-dioxane. Compound 4 was obtained
as a brownish yellow powder in 68% yield, M.P. 89–91 °C;
IR(KBr) m (cm-1): 2920, 2851 (aliphatic CH stretching),
Equimolar amounts (0.005 mol) of 3a and hydroxylamine
hydrochloride in 30 mL of 1,4-dioxane containing sodium
acetate (0.006 mol) was refluxed for 6 h. The reaction
mixture was concentrated, cooled and then poured into cold
water. The solid produced was filtered off, dried and
recrystallized from acetic acid. Compound 6 was obtained
as a pale green powder in 79% yield, M.P. 90–92 °C; IR
(KBr) m (cm-1): 3325 (OH), 2920, 2850 (aliphatic CH
1
1
1705 (C=O), and 1596 (C=N stretching); H-NMR spec-
stretching) and 1597 (C=N–O sharp); H-NMR spectrum
trum (DMSO-d6) showed signals at d; 6.6–7.3 (m, 5H,
aromatic CH), 2.7 (s, 3H, CH3-C=O), 1.2-1.6 (m, 32H,
16CH2 of alkyl chain), 0.88 (t, 3H, CH3); 13C NMR
(DMSO-d6) d (ppm): 198.5 (C=O ketonic), 173, 168
(2C=O cyclic), 155, 143, 137 (3C=N), 128.0 (3C), 128.9
(2C), 135 (aromatic CH), 26.4(CH3C=O), beside sp3 car-
bons of the aliphatic side chain 14.1 (terminal CH3), 22.7,
28.5, 29.3(2C), 29.6 (10C), 30.9, 31.9; MS m/z [% rel.int.]:
551 (M? -2, 4.6), 353(31.3), 141(88.7), 115(100). Anal.
Calcd. (%) for C30H43N5O3S : C; 65.07, H; 7.83, N; 12.65,
S; 5.79. Found: C; 65.26, H; 8.02, N; 12.97, S;5.98.
(DMSO-d6) showed signals at d; 4.02 (s, 1H, OH) which
disappeared on addition of D2O, 2.16 (s, 3H, CH3C=N),
1.2–1.6 (m, 32H, 16CH2 of alkyl chain), 0.88 (t, 3H, CH3);
13C NMR (DMSO-d6) d (ppm): 206, 177 (2C=O), 171,
168, 155 (3C=N), 158.9 (C–OH), 100.5 (= C–N=N– of
isoxazole ring), 10.0 (CH3C=N), beside sp3 carbons of
aliphatic side chain 14.1 (terminal CH3), 22.7, 28.5,
29.3(2C), 29.6 (10C), 30.9, 31.9; MS m/z [% rel.int.]: 449
(M?, 0.9), 353(19.4), 312(17.6), 115(100). Anal. Calcd.
(%) for C23H39N5O2S: C; 61.44, H; 8.74, N; 15.58, S; 7.13.
Found: C; 61.67, H; 8.89, N; 15.79, S; 7.19.
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J Surfact Deterg (2012) 15:179–190
Synthesis of 5-(5-heptadecyl-[1,3,4]thiadiazol-2-ylazo)-
2-mercapto-6-methyl-pyrimidin-4-ol (7)
Preparation of Nonionic Surfactants
from the Synthesized Heterocyclic Compounds
To a solution of 3a (0.005 mol) in 40 mL of ethanolic
sodium ethoxide solution (0.005 mol) of thiourea was
added. The reaction mixture was boiled under reflux for
7 h, concentrated and the residue was triturated with
cold water. The solid was collected by filtration, dried
and recrystallized from ethanol. Compound 7 was
obtained as a pale yellow powder in 74% yield, M.P.
98–100 °C; IR(KBr) m (cm-1): 3380 (OH), 3277–3176
(NH), 2919, 2850 (aliphatic CH stretching), 2682 (SH),
Propoxylation (Hydroxylation)
The hydrophobe of the synthesized compounds containing
0.5% KOH was stirred and heated to 70 °C while passing a
slow stream of nitrogen through the system to flush out
oxygen. Nitrogen addition was stopped and propylene
oxide added dropwise with continuous stirring and heating
under an efficient reflux system to retain propylene oxide.
The reactions were conducted for different intervals of time
ranging from 1 to 10 h. the apparatus was then filled with
nitrogen, cooled and reaction vessel weighed. The amount
of propylene oxide which was reacted and the average
degree of propoxylation were determined through the
increment in mass of the reaction mixture (increase in
weight of the mixture after the addition of propylene oxide
is the average amount of propoxylation) [42]. The selected
average numbers of moles, n, were 3, 5 and 7.
1
1614 (C=N stretching), 1080 (C=S); H-NMR spectrum
(DMSO-d6) showed signals at d; 5.56 (s, 1H, OH) which
disappeared on addition of D2O, 4.9 (s,H,NH) which
disappeared on addition of D2O, 2.12 (s, 3H, CH3-C=N),
1.2–1.6 (m, 32H, 16CH2 of alkyl chain), 0.88 (t, 3H,
CH3); 13C NMR (DMSO-d6) d (ppm): 183.1 (C–OH),
180.4 (C=S), 168, 173, 164 (3C=N), 58.3 (= C–N=N– of
pyrimidine ring), 17.8 (CH3C=N), beside sp3 carbons of
aliphatic side chain 14.1 (terminal CH3), 22.7, 28.5,
29.3(2C), 29.6 (10C), 30.9, 31.9; MS m/z [% rel.int.]:
492 (M??2, 4.4), 239(11.6), 128(44.4), 115(100). Anal.
Calcd. (%) for C24H40N6OS2: C; 58.50, H; 8.18, N;
17.06, S; 13.02. Found: C; 58.71, H; 8.29, N; 17.15,
S;13.14.
Surface Active Properties of Surfactants
Surface and Interfacial Tensions [43]
Surface tension and interfacial tension were measured
using a Du-Nouy tensiometer (Kru¨ss type 8451), for vari-
ous concentrations of the synthesized surfactants
(0.05–10-6 mol/L) and at 25 °C.
Synthesis of 2-(5-Heptadecyl-[1,3,4]thiadiazol-2-yl)-1,2-
dihydro-3-oxa-1,2-diaza-cyclopenta[a]naphthalene (8)
A solution of 1 (0.01 mol) in concentrated hydrochloric
acid (20 mL) and (10 mL) water was treated with a cold
saturated solution of sodium nitrite (0.7 gm) through 1 h
with stirring and cooling at 0–5 °C for 2 h to form the
diazonium salt (2). An alkaline solution of 2-naphthol
(prepared by dissolving 1.44 gm in 30 mL of 10% NaOH)
was added to the diazonium salt dropwise with continuous
stirring for half an hour. A brown solid product was
obtained, filtered off, dried and recrystallized from ethanol.
Compound 8 was obtained as a yellowish orange powder in
79% yield, M.P. 88–90 °C; IR(KBr) m (cm-1): 3380 (OH),
3043 (aromatic CH), 2920, 2850 (aliphatic CH stretching),
Cloud Point
The cloud point, a measure of inverse solubility charac-
teristic of nonionic surface active agents, was determined
by the gradual heating of a solution in a controlled tem-
perature bath, by determining the temperature at which the
clear or nearly clear solutions become definitely turbid.
Cooling the solutions until they become clear again,
allowed us to check the reproducibility of this temperature
[44].
1
1600 (N=N); H-NMR spectrum (CDCl3) showed signals
at d; 6.7–7.2 (m, 6H, 6H aromatic), 5.56 (s, 1H, OH) which
disappeared on addition of D2O, 1.2–1.6 (m, 32H, 16CH2
of alkyl chain), 0.9 (t, 3H, CH3); MS m/z [% rel.int.]: 491
(M? -3, 0.5), 239 (13.10), 115(39.20), 59 (100). Anal.
Calcd. (%) for C29H42N4OS: C; 70.40, H; 8.56, N; 11.32,
S; 6.48. Found: C; 70.55, H; 8.88, N; 11.54, S; 6.77.
Wetting Time
The wetting power of the tested surfactants were deter-
mined by immersing a sample of cotton fabric in a 1.0 wt%
aqueous solution of the surfactants and measuring the
sinking time in second [45].
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J Surfact Deterg (2012) 15:179–190
189
6. Hegmann T, Neumann B, Wolf R (2005) Liquid crystalline
paracyclophanes and ansa compounds-series of polyether mac-
rocycles incorporating diacetylene, phenyl, biphenyl, p-terphenyl
and 2,5-diphenyl-1,3,4-thiadiazole rigid cores. J Mater Chem
15:1025–1034
Foaming Properties
The foamability was measured by the Ross-Miles method
[46]. The foam production for a 1.0 wt% solution was
measured by the foam height initially produced.
7. Rees CW, Sivadasan S (2002) Synthesis of 1,3,4-thiadiazole
oligomers. J Chem Soc Perkin Trans 1:1543–1547
8. Tao Y, Xu Q, Lu J, Yang X (2010) The synthesis, electro-
chemical and fluorescent properties of monomers and polymers
containing 2,5-diphenyl-1,3,4-thiadiazole. Dyes and Pigments
84:153–158
Emulsion Stability
9. Aamir M, Kumar S (2007) Synthesis and evaluation of anti-
inflammatory, analgesic, ulcerogenic and lipid peroxidation
properties of ibuprofen derivatives. Acta Pharm 57:31–45
10. Radwan MA, Ragal EA, Sabry NM, El-Shenawy SM (2007)
Synthesis and biological evaluation of new 3-substituted Indole
derivatives as potential anti-inflammatory and analgesic. Bioorg
Med Chem 15:3832–3841
The emulsion was prepared from 10 mL of a 20 mmol
aqueous solution of surfactant and 5 mL of toluene at
40 °C. The emulsifying capacity was taken as the time it
took for an aqueous volume separating from the layer to
reach 9 mL counting from the moment of shaking [47].
11. Ahmed SM, Ahmed F, Osman SM (1985) Preparation and
characterization of derivatives of isoricinoleic acid and their
antimicrobial activity. J Am Oil Chem Soc 62:1578–1580
12. Al-Qahtani A, Siddiqui YM (2009) Inhibition of growth of
Leishmania donovani promastigotes by newly synthesized
1,3,4-thiadiazole analogs. J Saudi Pharm Soc 16:227–232
13. Bayrak H, Demirbas A, Karaoglu SA, Demirbas N (2009) Syn-
thesis of some new 1,2,4-triazoles, their Mannich and Schiff
bases and evaluation of their antimicrobial activities. Eur J Med
Chem 44:1057–1066
Biodegradability
Samples which were taken daily or more frequently and
these were filtered through filter paper before measuring
the surface tension. Surface tension measurements were
made periodically (each day) on each sample during the
degradation test [48]. The biodegradation percentage (D)
for each sample was calculated using the following
equation.
14. Almasirad A, Tabatabai SA, Faizi M (2004) Synthesis and anti-
convulsant activity of new 2-substituted-5-[2-(2-fluorophen-
oxy)phenyl]-1,3,4-oxadiazoles and 1,2,4-triazoles. Bioorg Med
Chem 14:6057–6059
D ¼ ½ct ꢁ c0=cbt ꢁ c0ꢂ ꢃ 100
15. Rauf A, Sharma S, Gangal S (2008) One-pot synthesis, antibac-
terial and antifungal activities of novel 2,5-disubstituted-1,3,
4-oxadiazoles. Chin Chem Lett 19:5–8
where ct = Surface tension at time t.
c0 = Surface tension at time zero (initial S.T).
cbt = Surface tension of the blank experiment at time
t (without sample).
16. Oruc EE, Rallas S (2004) 1,3,4-thiadiazole derivatives. Synthesis,
structure elucidation, and structure-antituberculosis activity
relationship investigation. J Med Chem 47:6760–6767
17. Cerecetto H, Dimaio R (2000) Synthesis and antitrypanosomal
evaluation of E-isomers of 5-nitro-2-furaldehyde and 5-nitro-
thiophene-2-carboxaldehyde semicarbazone derivatives. Struc-
ture–activity relationships. Eur J Med Chem 35:343–350
18. Cerecetto H, Dimaio R (2004) Design, synthesis and biological
evaluation of new potent 5-nitrofuryl derivatives as anti-trypan-
osoma cruzi agents. Studies of trypanothione binding site of
trypanothione reductase as target for rational design. Eur J Med
Chem 39:421–431
References
1. Yamamoto T, Uemura T, Tanimoto A (2003) Synthesis and
chemical properties of p-conjugated poly(imidazole-2,5-diyl)s.
Macromolecules 36:1047–1053
2. Yamamoto T, Arai M, Sasaki S (2003) Copolymers of thiophene
and thiazole regioregulation in synthesis, stacking structure, and
optical properties. Macromolecules 36:7986–7993
19. Carvalho SA, Silva EF (2004) Synthesis and antitrypanosomal
profile of new functionalized 1,3,4-thiadiazole-2-arylhydrazone
derivatives, designed as non-mutagenic megazol analogues.
Bioorg Med Chem Lett 14:5967–5970
20. Mahy PJ, Gaspard S, Mansuy D (1993) Phenylhydrazones as new
good substrates for the dioxygenase and peroxidase reactions of
prostaglandin synthase: Formation of iron(III)-.sigma.-phenyl
complexes. BioChem 32:4014–4021
21. Prusis P, Dambrava M, Andrianov V (2004) Synthesis and
quantitative structure-activity relationship of hydrazones of
N-amino-N‘-hydroxyguanidine as electron acceptors for xanthine
oxidase. J Med Chem 47:3105–3110
3. Yasuda T, Imase T, Sasaki S (2005) Synthesis, solid structure,
and optical properties of new thiophene-based alternating p-conju-
gated copolymers containing 4-alkyl-1,2,4-triazole or 1,3,4-thiadi-
azole unit as the partner unit. Macromolecules 38:1500–1503
4. Liou G, Hsiao S, Chen W (2006) A new class of high Tg and
organosoluble aromatic poly(amine-1,3,4-oxadiazole)s contain-
ing donor and acceptor moieties for blue-light-emitting materials.
Macromolecules 39:6036–6045
22. Carvalho SA, Lopes FA (2008) Studies toward the structural
optimizations of new brazillizone related trypanocidal 1,3,
4-thiadiazole-2-arylhydrazone derivatives. Bioorg Med Chem
16:413–421
23. Amine MS, Eissa AMF, Elsawy AA, Shaaban AF, El Sayed R
(2004) New heterocycles having double characters as
5. Yasuda T, Imase T, Nakamura Y (2005) New alternative donor-
acceptor arranged poly(aryleneethynylene)s and their related
compounds composed of five-membered electron-accepting
1,3,4-thiadiazole, 1,2,4-triazole, or 3,4-dinitrothiophene units:
synthesis, packing structure, and optical properties. Macromole-
cules 38:4687–4697
123

190
J Surfact Deterg (2012) 15:179–190
antimicrobial and surface active agents. Part 1: nonionic com-
pounds from fatty acid isothiocyanate. Grasas
55:370–377
39. Takeshi H (1970) Studies of ester containing surfactant: prepa-
ration and properties of sodium sulphalkanoates. Bull Chem Soc
43:2236–2239
y Aceites
24. Amine MS, Eissa AMF, El Sawy AA, Shabaan AF, El-sayed R
(2003) New heterocycles having double characters as antimi-
crobial and surface active agents. Part 2: Anionic compounds
from fatty acid isothiocyanate. Chem Indian J 1:313–319
25. Amine MS, Eissa AMF, Elsawy AA, Shaaban AF, El Sayed R
(2004) New heterocycles having double characters as antimi-
crobial and surface active agents. Part 3: Non-ionic compounds
from fatty acid hydrazide. OLAJ Szappan Kozmetika 53:124–128
26. Amine MS, Aly AA, El-Sayed R (2006) Synthesis and surface active
properties of condensed and non-condensed quinazoline derivatives
of industrial applications. Indian J Chem 45B:1020–1027
27. Amine MS, Hebash KA, Ahmed MHM, El-Sheikh AA (2006)
New heterocyclic having double characters as antimicrobial and
surface active agents. Part 5: new quinazoline derivatives from
stearic acid. OLAJ Szappan Kozmetika 55:121–125
28. Amine MS, Ahmed MHM, Hebash KA, El-Sheikh AA (2007)
New heterocycles having double characters as antimicrobial and
surface active agents. Part 6: Novel thiadiazole from stearic acid.
OLAJ Szappan Kozmetika 56:57–61
29. Amine MS, Ahmed MHM, Hebash KA, El-Sheikh AA (2010)
Utilization of stearic acid in heterocyclic synthesis part 8 : syn-
thesis of some new thiadiazoles and triazoles of industrial
applications. OLAJ Szappan Kozmetika 59:30–34
40. Seong KT, Toshiyaki K, Toshikozu NH, Ikeda JI (1996) Surface-
active properties of novel cationic surfactants with two alkyl
chains and two ammonio groups.
73:907–911
J Am Oil Chem Soc
41. Eter ET, Richard RE, David A (1974) Biodegradable surfactants
derived from corn starch. J Am Oil Chem Soc 51:486–494
42. Eissa AMF (2007) Synthesis and evaluation of some surface
active agents from long chain fatty amine. Grasas y Aceites
58:379–389
43. Wiel JK, Smith FD, Stirton AJ, Bistine RG (1963) Long chain
alkanesulphonates and 1-hydroxy-2-alkanesulphonates: Structure
and property relations. J Am Oil Chem Soc 40:538–541
44. Durham K (1961) Properties of detergent solutions-amphipathy
and adsorption. Surf Activity Deterg 1:1–28
45. Draves CZ, Clarkson R (1931) A new method for the evaluation
of wetting agents. J Am Dye Stuff Report 20:201
46. Ross J, Milles GD (1941) Apparatus for comparison of foaming
properties of soaps and detergents. Oil Soap 18:99–102
47. Scholnick F, Linfield WM (1977) Lactose-derived surfactants
(III): fatty esters of oxyalkylated lactitol. J Am Oil Chem Soc
54:430–435
48. Falbe J (1986) Surfactants for consumer. 4:139–141
30. Amine MS, Ahmed MHM, Hebash KA, El-Sheikh AA (2010)
Utilization of fatty acids in heterocyclic synthesis part 9 : dual
activity of novel triazoles as antimicrobial and surface active
agents. OLAJ Szappan Kozmetika 59:49–55
Author Biographies
Mahasen Saad Amine received her B.Sc. and M.Sc. degrees from
Ain Shams University, and her Ph.D. degree from Zagazig University
in Egypt. She is a professor of organic chemistry at the Faculty of
Science at Benha University. Her research interests are in organic
synthesis, particularly surfactants with a heterocyclic moiety.
31. Kornis G (1996) 1,3,4-Thiadiazoles, Comprehensive Heterocy-
clic Chemistry. In: Katritzky AR, Rees CW (eds) vol 4. Perg-
amon, Oxford pp 387–407
32. Koutentis PA, Constantinides CP (2008) 1,3,4-Thiadiazoles,
Comprehensive Heterocyclic Chemistry. In: Katritzky AR (eds)
vol 5. Pergamon, Oxford pp 573–600
Amal Ahmed Mahmoud is a professor of organic chemistry at the
Faculty of Science at Benha University in Egypt. She received her
M.Sc. and Ph.D. degrees from Zagazig University. Her research
interest is in the field of organic synthesis, particularly polymeric
surfactants having a heterocyclic moiety.
33. Bauer AW, Kirby WM, Sherris C, Turck M (1966) Antibiotic
susceptibility testing by a standardized single disk method. Am J
Clinical Pathology 45:493–496
34. Pfaller MA, Burmeister L, Bartlett MA, Rinaldi MG (1988)
Multicenter evaluation of four methods of yeast inoculum prep-
aration. J Clin Microbiol 26:1437–1441
35. Ahmed MMH, Sallay P, Rusznak I, Farkas L (1996) Determi-
nation of the average ethoxylation degree. Tenside Surf Det
33:410–411
36. Findly A (1963) Practical physical chemistry, 6th edn. Longman,
London, pp 1040–1069
Samy Khodary Badr is a lecturer in organic chemistry at the Faculty
of Science at Benha University in Egypt. He received his M.Sc. and
Ph.D. degrees from Zagazig University. His research is in the field of
polymeric surfactants having heterocyclic moieties and applied
organic chemistry.
37. Chlebicki J, Sokołowski A (1991) Adsorption of n-alkylthiooli-
gooxypropylene glycols at aqueous solution-air interface. Colloids
Surf 56:251–261
38. Ahmed MHM (2004) Preparation and surface active properties of
novel succinic acid based surfactants. OLAJ Szappan Kozmetika
53:23–28
Alaa Salah Gouda is a teaching assistant at the Faculty of Science at
Benha University in Egypt. He received his B.Sc. and M.Sc. degrees
from Benha University. He is working in the field of organic synthesis
and synthetic surfactants having a heterocyclic moiety.
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