Fatty acids in heterocyclic synthesis. Part XIV: Synthesis of surface active agents from some novel class of oxadiazole, thiadiazole and triazole derivatives having microbiological activities

Article abstract of DOI:10.1007/s11743-013-1530-9

Reaction of stearic acid with semicarbazide in refluxing POCl₃ afforded 2-amino-5-heptadecyl 1,3,4-oxadiazole. Acylation of the amino group with acetic anhydride, ethyl chloroacetate and chloroacetic acid gave amide and β-amino acid derivatives. These compounds were cyclized to imidazo[2,1-b]oxadiazole derivatives by two different techniques. Treating the starting oxadiazole compound with P₂S₅, hydroxyl amine and hydrazine hydrate in benzene afforded thiadiazole and triazole derivatives. Unexpectedly, triazolo[3,4-b][1,3,4]oxadiazole derivative was obtained when 1,3,4-oxadiazole derivative was refluxed with hydrazine hydrate in ethanol. The biological activities of the synthesized compounds were screened in vitro against some gram positive and gram negative bacteria and fungi. Addition of quantitative amount of propylene oxide units (3, 5, 7 mol) to the synthesized compounds afforded new nonionic surfactants. The physico-chemical and surface properties of the novel synthesized surfactants such as surface and interfacial tension, cloud point, wetting time, emulsion stability, foam height, CMC, resistance to hydrolysis and their biodegradability were investigated. In addition, surface parameters including effectiveness (π _CMC), efficiency (PC₂₀), maximum surface excess (Γ_max) and (A _min) were examined.

Full text of DOI:10.1007/s11743-013-1530-9

J Surfact Deterg (2014) 17:509–523
DOI 10.1007/s11743-013-1530-9
ORIGINAL ARTICLE
Fatty Acids in Heterocyclic Synthesis. Part XIV: Synthesis
of Surface Active Agents from Some Novel Class
of Oxadiazole, Thiadiazole and Triazole Derivatives
Having Microbiological Activities
•
Iman A. Gad El-Karim Mahasen S. Amine
•
•
Amal A. Mahmoud Alaa S. Gouda
Received: 17 March 2013 / Accepted: 29 August 2013 / Published online: 24 September 2013
Ó AOCS 2013
Abstract Reaction of stearic acid with semicarbazide in
refluxing POCl3 afforded 2-amino-5-heptadecyl 1,3,4-
oxadiazole. Acylation of the amino group with acetic
anhydride, ethyl chloroacetate and chloroacetic acid gave
amide and b-amino acid derivatives. These compounds
were cyclized to imidazo[2,1-b]oxadiazole derivatives by
two different techniques. Treating the starting oxadiazole
compound with P2S5, hydroxyl amine and hydrazine
hydrate in benzene afforded thiadiazole and triazole
derivatives. Unexpectedly, triazolo[3,4-b][1,3,4]oxadiazole
derivative was obtained when 1,3,4-oxadiazole derivative
was refluxed with hydrazine hydrate in ethanol. The bio-
logical activities of the synthesized compounds were
screened in vitro against some gram positive and gram
negative bacteria and fungi. Addition of quantitative
amount of propylene oxide units (3, 5, 7 mol) to the syn-
thesized compounds afforded new nonionic surfactants.
The physico-chemical and surface properties of the novel
synthesized surfactants such as surface and interfacial
tension, cloud point, wetting time, emulsion stability, foam
height, CMC, resistance to hydrolysis and their biode-
gradability were investigated. In addition, surface param-
eters including effectiveness (pCMC), efficiency (PC20),
maximum surface excess (Cmax) and (Amin) were examined.
Keywords Stearic acid ꢀ 2-Aminooxadiazole ꢀ
Nonionic surfactant ꢀ Antimicrobial ꢀ Triazolo[3,4-
b]oxadiazole ꢀ Imidazo[3,1-b]oxadiazole ꢀ
Thiadiazole ꢀ Triazole ꢀ Surface properties
Introduction
2-Amino oxadiazoles have a great importance in biological
and industrial applications. They have bactericidal, fungi-
cidal [1], herbicidal, and insecticidal activities [2]. In
addition, they are employed as anti-inflammatory [3],
analgesic [4], anticonvulsant, nervous system depressant
[5], antiallergic [6] and antiviral drugs [7]. Conjugated
systems of 2,5-disubstituted-[1,3,4]oxadiazoles often fluo-
resce, such a property makes them potentially useful as
laser dyes, optical brighteners, scintillators, luminescent
dyes and photosensitizing materials [8]. Having a long
alkyl chain (hydrophobic part) attached to the oxadiazole
nucleus increases their usefulness even further. Moreover,
the introduction of a quantitative amount of hydrophilic
part such as polyoxyethylene, or polyoxypropylene
increases the solubility of 1,3,4-oxadiazoles in water and
enhances the potential of their usage as nonionic surfac-
tants. Generally, surfactants are one of the most important
and widely used products in nearly every industrial sector.
The growing and diverse applications of nonionic surfac-
tants in therapy [9], industry [10], agriculture [11] and
housing [12] prompted us to continue our research program
on the utilization of fatty acids in heterocyclic synthesis, to
synthesize novel nonionic surfactants [13–17]. Herein, we
report the synthesis and some reactions of 2-amino-5-
heptadecyl[1,3,4]oxadiazole (1) and the physico-chemical
and surface properties of the novel synthesized surfactants.
Electronic supplementary material The online version of this
article (doi:10.1007/s11743-013-1530-9) contains supplementary
material, which is available to authorized users.
I. A. Gad El-Karim (&) ꢀ M. S. Amine ꢀ
A. A. Mahmoud ꢀ A. S. Gouda
Department of Chemistry, Faculty of Science, Benha University,
P.O.:13518, Benha, Egypt
e-mail: i.elkarim@gmail.com
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Experimental Protocols
hydrochloride (0.01 mol) in (20 mL) POCl3 was refluxed
for 8 h. The reaction mixture was concentrated, cooled, and
then poured onto ice while stirring. The produced solid was
filtered off and recrystallized from ethanol. Compound 1
was obtained as a pale yellow powder in 77 % yield, mp
102–104 °C. Anal. Calc. (%) for C19H37N3O: C; 70.54, H;
11.53, N; 12.99. Found: C; 70.23, H; 11.29, N; 12.81.
Synthesis of (4-chloro-benzylidene)-(5-heptadecyl-
Materials
Stearic acid (Chemajet Chemical Company, 99 % GPR),
semicarbazide hydrochloride (Winlab, 99 %), POCl3 (Alpha
Chemie, C98 %), 4-chlorobenzaldehyde [Fluka Chemika,
C98 % (NT), piperidine (Merck Schuchardt,[98 % (GC)],
acetic anhydride (Adwic, 98 %), ethyl chloroacetate (Loba
Chemie, [98 %), chloroacetic acid [Aldrich, 99 % (T)],
pyridine (LR) [SD Fine-Chem Limited, 99 % (GC)], glacial
acetic acid (S D Fine-Chem Limited, 99 %), phosphorous
pentasulfide (Sigma-Aldrich, 95 %), hydroxylamine
hydrochloride (Winlab, 98 %), hydrazine hydrate (Loba
Chemie, 80 %), benzene, toluene (Adwic), ethanol abs.
(Adwic, 99 %), methanol (S D Fine-Chem Limited, 99 %).
paraffin oil (Aldrich, dynamic viscosity; 110–230 mPa s,
density; 0.827–0.890 g/mL at 20 °C).
[1,3,4]oxadiazol-2-yl)-amine (2).
A
mixture of
1
(0.01 mol) and 4-chlorobenzaldehyde (0.01 mol) in etha-
nol (30 mL) in the presence of piperidine (0.5 mL) was
refluxed for 6 h. The reaction mixture was concentrated,
cooled and poured into ice-HCl. The obtained solid product
was filtered off, dried and recrystallized from ethanol.
Compound 2 was obtained as a white powder in 81 %
yield, mp 136–138 °C. Anal. Calc. (%) for C26H40ClN3O:
C; 70.01, H; 9.04, N; 9.42, Cl; 7.95. Found: C; 70.13, H;
9.29, N; 9.61, Cl; 8.05.
Synthesis of N-(5-heptadecyl-[1,3,4]oxadiazol-2-yl)-
acetamide (3). First, 0.01 mol of 1 was refluxed in 30 mL
of acetic anhydride for 3 h. The reaction mixture was
concentrated, poured into cold water (30 mL). The solid
product obtained was filtered off, dried and recrystallized
from acetic acid. Compound 3 was obtained as a deep
brown powder in 75 % yield, mp 85–87 °C. Anal. Calc.
(%) for C21H39N3O2: C; 69.00, H; 10.75, N; 11.49. Found:
C; 69.13, H; 10.29, N; 11.61.
Structure Confirmation
The structural assignments of new compounds are based on
1
their elemental analysis and spectral data (IR, H NMR,
13C NMR, and Mass spectra) (Full description of the
obtained data are presented in the supplementary material
section). All melting points are uncorrected and determined
by the open capillary method using a Gallenkamp melting
point apparatus.
Synthesis of 2-chloro-N-(5-heptadecyl-[1,3,4]oxadiazol-
2-yl)-acetamide (4). A mixture of 1 (0.01 mol) and ethyl
chloroacetate (0.01 mol) in ethanol (30 mL) was refluxed
for 8 h. The reaction mixture was concentrated and cooled.
The solid product was filtered off, dried and recrystallized
from ethanol. Compound 4 was obtained as a pale brown
powder in 85 % yield, mp 132–134 °C. Anal. Calc. (%) for
C21H38ClN3O2: C; 63.06, H; 9.58, N; 10.51, Cl; 8.86.
Found: C; 63.23, H; 10.19, N; 10.62, Cl; 8.65.
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-460?
1
(Japan). H- and 13C-NMR spectra were recorded in deu-
terated chloroform (CDCl3) or dimethyl sulfoxide (DMSO-
d6) as a solvent on a Varian Mercury VXR-300 spec-
trometer (200 MHz for 1H NMR and 75 MHz for 13C
NMR) using TMS as internal reference. Chemical shifts are
expressed in ppm. The mass spectra of compounds 1, 7, 11
and 12 were recorded on a Shimadzu GCMS-QP-1000EX
mass spectrophotometer and those of 2–6 and 8–10 were
recorded on a Shimadzu QP-2010 Plus mass spectropho-
tometer at 70 eV.
Synthesis
of
2-[(5-heptadecyl-[1,3,4]oxadiazol-2-
yl)amino]acetic acid (5). A mixture of 1 (0.01 mol) and
chloroacetic acid (0.01 mol) in benzene (30 mL) in the
presence of piperidine (0.5 mL) was refluxed for 7 h. The
reaction mixture was concentrated, cooled and poured into
ice-HCl. The solid product obtained was filtered off, dried
and recrystallized from benzene. Compound 5 was
obtained as a pale gray powder in 71 % yield, mp
126–128 °C. Anal. Calc. (%) for C21H39N3O3: C; 66.14, H;
10.24, N; 11.02 Found: C; 66.45, H; 10.51, N; 10.69.
Synthesis of 2-heptadecylimidazo[2,1-b][1,3,4]oxa-
diazol-6(5H)-one (6). Initially, 0.01 mol of 4 was refluxed
with benzene (30 mL) in the presence of pyridine (0.5 mL)
for 5 h or subjected to fusion in an oil bath at 170 °C for
2 h. The reaction mixture was concentrated, cooled and
poured into ice-HCl. The obtained solid product was fil-
tered off, dried and recrystallized from ethanol. Compound
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, Benha University, Egypt. Antibacterial and anti-
fungal activities were carried out in the Micro Analytical
Center, Faculty of Science, Cairo University.
Synthesis
Synthesis of 2-amino-5-heptadecyl-1,3,4-oxadiazole (1). A
mixture of stearic acid (0.01 mol) and semicarbazide
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511
6 was obtained as yellow powder in 70 % yield, mp
149–151 °C. Anal. Calc. (%) for C21H37N3O2: C; 69.38, H;
10.26, N; 11.56. Found: C; 69.55, H; 10.41, N; 11.68.
Synthesis of 2-heptadecylimidazo[2,1-b][1,3,4]oxa-
diazol-5(6H)-one (7). (0.01 mol) of 5 was refluxed in
(30 mL) glacial acetic acid containing sodium acetate
(0.01 mol) for 5 h or fused in an oil bath at 170 °C for 2 h.
The reaction mixture was concentrated, cooled and poured
into ice with stirring. The solid product obtained was fil-
tered off, washed several times with water and recrystal-
lized from ethanol. Compound 7 was obtained as a gray
powder in 68 % yield, mp 161–163 °C. Anal. Calc. (%) for
C21H37N3O2: C; 69.38, H; 10.26, N; 11.56. Found: C;
69.55, H; 10.41, N; 11.68.
Anal. Calc. (%) for C20H37N5O: C; 66.08, H; 10.26, N;
19.26. Found: C; 66.14, H; 10.31, N; 19.31.
Compound 12 was obtained as a pale yellow powder in
73 % yield, mp 98–100 °C. Anal. Calc. (%) for
C21H45N5O: C; 65.75, H; 11.82, N; 18.26. Found: C; 65.58,
H; 12.01, N; 18.39.
Antimicrobial Activities
The antimicrobial susceptibility or resistance profile of the
synthesized compounds was determined with the modified
Kirby-Bauer disc diffusion technique [18–21], using Mu-
eller–Hinton agar.
One hundred microliters of the test bacteria/fungi were
grown in 10 mL of fresh media until they reached a count
of approximately 108 cells/mL for bacteria and 105 cells/
mL for fungi. The microbial suspension (100 ll) was
spread onto agar plates that are relevant to the broth in
which they are maintained. Standard discs of Tetracycline
(Antibacterial agent), Amphotericin B (Antifungal agent)
were used as positive control for antimicrobial activity,
while filter discs impregnated with 10 ll of solvent (dis-
tilled water, chloroform, DMSO) were used as a negative
control. Blank paper discs (Schleicher and Schuell, Spain)
with a diameter of 8.0 mm were impregnated with 10 ll of
the tested concentration.
Synthesis of 2-amino-5-heptadecyl-1,3,4-thiadiazole (8).
A mixture of 1 (0.01 mol) and phosphorous pentasulfide
(0.02 mol) was refluxed in (30 mL) dry xylene until the
color changes into orange. The reaction mixture was
filtered while hot and the filtrate was left to cool at room
temperature. The obtained solid was filtered off, dried
and recrystallized from benzene. Compound 8 was
obtained as a yellow powder in 80 % yield, mp
110–112 °C. Anal. Calc. (%) for C19H37N3S: C; 67.20,
H; 10.98, N; 12.37, S; 9.44. Found: C; 66.91, H; 10.64,
N; 12.08, S; 9.13.
Synthesis of 3-amino-5-heptadecyl[1,2,4]triazol-4-ol
(9). A mixture of 1 (0.01 mol) and hydroxylamine hydro-
chloride (0.01 mol) was refluxed in (30 mL) pyridine for
4–5 h. The reaction mixture was cooled and poured into
ice-HCl. The solid product obtained was filtered off, dried
and recrystallized from benzene. Compound 9 was
obtained as a greenish black powder in 69 % yield, mp
104–106 °C. Anal. Calc. (%) for C19H38N4O: C; 67.41, H;
11.31, N; 16.55. Found: C; 67.53, H; 11.22, N; 16.78.
Synthesis of 5-heptadecyl[1,2,4]triazole-3,4-diamine
(10). A mixture of 1 (0.01 mol) and hydrazine hydrate
(0.01 mol) was refluxed in 30 mL of benzene for 6 h. The
reaction mixture was concentrated and cooled. The solid
was filtered off, dried and recrystallized from benzene.
Compound 10 was obtained as a yellowish brown powder
in 78 % yield, mp 94–96 °C. Anal. Calc. (%) for
C19H39N5: C; 67.61, H; 11.65, N; 20.75. Found: C; 67.54,
H; 11.41, N; 20.58.
When the filter paper disc impregnated with the tested
compound (of known concentration) was placed on agar,
the compound diffused from the disc into the agar in the
area around the disc. The solubility of the tested compound
and its molecular size determine the size of the area of its
infiltration around the disc. An organism that is susceptible
to the tested compound will not grow in the area around the
disc. The size of this inhibition zone is used as a measure of
the antimicrobial activity ‘‘A’’ of a tested compound at its
minimum inhibitory concentration (MIC). The observed
data on the antimicrobial activity of the compounds are
given in Table 1.
Preparation of Nonionic Surfactants
from the Synthesized Heterocyclic Compounds
Propoxylation (hydroxylation)
Synthesis of 6-heptadecyl[1,2,4]triazolo[3,4-b][1,3,4]
oxadiazol-3-amine (11) and ethyl-N-[amino(hydrazinylid-
ene)methyl]heptadecylhydrazonoate (12). A mixture of 1
(0.01 mol) and hydrazine hydrate (0.01 mol) was refluxed
in 30 mL of ethanol for 5–6 h. Compound 11 was obtained
directly on heating and separated, filtered off, dried and
recrystallized from acetic acid. While the filtrate was
concentrated, cooled then the solid 12 was filtered off,
dried and recrystallized from ethanol. Compound 11 was
obtained as a white powder in 69 % yield, mp 130–132 °C;
Following Morgos procedure [22], 0.5 wt% KOH solution
containing 0.01 mol of the synthesized compound was
stirred and heated to 70 °C while passing a slow stream of
nitrogen through the system to flush out oxygen. The
nitrogen stream was stopped and propylene oxide was
added drop-wise with continuous stirring and heating under
an efficient reflux system to retain the propylene oxide. The
reaction was conducted for different intervals of time
ranging from 1–10 h. The apparatus was then filled with
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Table 1 Antimicrobial activity of compounds 1–12
Sample
Inhibition zone diameter (mm/mg sample)
Escherichia coli G- Staphylococcus aureus G?
Aspergillus flavus Fungus
Candida albicans Fungus
MIC
–
A
MIC
–
A
MIC
–
A
MIC
–
A
Control: DMSO
0.0
0.0
0.0
0.0
Positive reference
Tetracycline
200
–
31
–
200
–
30
–
–
–
–
–
Amphotericin B
200
400
400
400
400
400
400
400
400
400
400
400
400
16
200
400
400
400
400
400
400
400
400
400
400
400
400
19
1
100
200
200
400
400
400
400
100
100
100
100
200
14
11
10
12
11
15
14
14
13
18
16
12
200
200
100
200
100
100
200
200
400
200
200
100
13
11
11
11
10
14
13
15
13
15
14
11
0.0
0.0
0.0
0.0
0.0
11
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
12
2
3
4
5
6
7
12
8
0.0
0.0
0.0
13
9
10
11
12
11
0.0
0.0
A = 0.0, Not active; A \ 7 mm, slightly active; A [ 15 mm, moderately active; A [ 20 mm, highly active
MIC minimum inhibitory, A antimicrobial activity of tested compounds; concentration
nitrogen and cooled. The reaction vessel was weighed. The
amount of reacted propylene oxide and the average degree
of propoxylation were determined from the increment in
the mass of the reaction mixture [23]. The selected average
numbers of moles, n, are 3, 5 and 7.
and the solution was allowed to cool down until it became
clear again. The process was repeated to check the repro-
ducibility of the recorded temperature.
Wetting Time
Surface Active Properties of Surfactants
Wetting time was measured by immersing a cotton skein
(1 g) in a 0.1 wt% solution of the prepared surfactants in
distilled water at 25 °C according to the Draves technique
[28]. The sinking time was measured in seconds.
Surface and Interfacial Tensions
Surface and interfacial tension measurements on I(a–c)–
IX(a–c) were carried out according to Findlay [24] with a
Kru¨ss tensiometer [25] (Kru¨ss GmbH, Hamburg, Instru-
ment Nr. K6) for different concentrations of the synthe-
sized surfactants (0.05–10-6 mol/L), using a platinum-
iridium ring at constant temperature (25 1 °C). Paraffin
oil was used for the interfacial tension measurements. The
tensiometer was calibrated using the method described in
ASTM Designation: D1331-01 [26].
Foaming Properties
Foam height was measured by the Ross Miles method [29].
In this procedure a given surfactant solution was allowed to
fall from a set height into the same surfactant solution in a
volumetric cylinder, hence creating foam. The height of the
foam was visually assessed.
Emulsion Stability
Cloud Point
The emulsifying property of the prepared surfactants was
determined as follows: In a 100-mL graduated stoppered
tube; an aqueous solution of the surfactant (10 mL,
20 mol) was mixed with light paraffin oil (6 mL). The
mixture was shaken vigorously by magnetic stirring
[Thermo scientific CimarecTM stirring hot plate, model
The cloud point is a measure of the inverse solubility of a
nonionic surface active agent. In a temperature-controlled
bath, a 1-wt% solution of the tested compound was grad-
ually heated until the clear or nearly clear solution became
definitely turbid [27]. The temperature was then recorded
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513
Minimum Surface Area (Amin
)
no: sp131320-30, estimated stirring speed (1,100 rpm)]
for 2 min at 25 °C. The tube was placed upright and the
separation of the formed emulsion was observed. The
time taken for the separation of (9 mL) of the aqueous
layer indicates the emulsion stability of the surfactant
[30].
Knowing Cmax, it is easy to calculate the effective area
occupied by each surfactant molecule adsorbed at the air/
water interface at surface saturation [35, 36]. The average
2
˚
area Amin (in A /mol) is given by Eq. (4):
ꢂ
1016
Amin
¼
ð4Þ
C
maxN
Critical Micelle Concentration (CMC) Measurements
where N Avogadro’s number 6.023 9 1023.
The critical micelle concentration (CMC) is the minimum
concentration at which surfactants molecules begin to form
micelles [31]. CMC values were obtained through a con-
ventional plot of the surface tension versus the logarithm of
concentration of surfactant. The CMC concentration cor-
responds to the point where the surfactant first shows the
lowest surface tension, and after which the surface tension
remains nearly constant.
Resistance to Hydrolysis
The resistance of a certain surfactant towards acid and base
hydrolysis was established by measuring the surface ten-
sion of that surfactant in acidic and alkaline media. Thus,
the surface tension of a 0.1 % solution of the surfactant in
5 % sulfuric acid or in 1 % sodium hydroxide was mea-
sured at room temperature after boiling for 30 and 60 min.
Effectiveness (pCMC
)
Biodegradability of the Synthesized Surfactants
The effectiveness of a certain surfactant pCMC is expressed
in terms of the decrease in the surface tension that is
induced by this surfactant at the critical micelle concen-
tration [32]. It is calculated from the difference between the
surface tension of pure water (c0) and the surface tension of
the surfactant solution at the critical micelle concentration
(cCMC), Eq. (1).
The biodegradation tests of the synthesized nonionic surfac-
tants were performed according to the River Water Die-Away
method [37]. The river water for testing was sampled from the
River Nile. In this test, a stirred solution containing the tested
surfactant (1,000 ppm) was incubated at 25 °C. Samples were
withdrawn daily, filtered using Whatman filter paper and the
surface tension was measured using a Du-Nouy tensiometer
(Kruss type K6). The process was repeated for 7 days. The
biodegradation percentage D% was calculated in terms of the
measured surface tension according to Eq. (5):
pCMC ¼ c0 ꢁ cCMC
ð1Þ
Efficiency (PC20)
Efficiency of a surfactant (PC20) is defined by the values of
the negative logarithm of the bulk concentration necessary
to reduce surface tension by 20 mN/m [33]. It can be cal-
culated from the following equation, Eq. (2).
D ¼ ½ðct ꢁ c0Þ=ðcbt ꢁ c0Þꢂ ꢃ 100
where ct surface tension at time t. c0 surface tension at time
zero (initial surface tension). cbt surface tension of the
blank experiment at time t.
ð5Þ
c ꢁ 20 ꢁ cCMC
PC20
¼
ꢁ log CCMC
ð2Þ
2:303nRT
where
R
universal gas constant 8.31 9 107 ergs
mol-1 K-1. T absolute temperature K.
Maximum Surface Excess Cmax
Results and discussion
In continuation of our research program on the utilization
of fatty acids in the synthesis of heterocyclic compounds as
precursors for novel nonionic surfactant [13–17], herein we
report the synthesis and some reactions of 2-amino-5-
heptadecyl[1,3,4]oxadiazole (1) (Scheme 1). Thus, the
reaction of stearic acid with semicarbazide hydrochloride
in refluxing POCl3 afforded 1 in good yield. Formation of 1
The values of the maximum surface excess Cmax
—
expressed in mol/cm2 were calculated from surface or
interfacial data by the use of Gibbs equation [34], Eq. (3):
ꢁ
ꢀ
ꢁ1
dc
Cmax
¼
RT
ð3Þ
2:303
d log C
T
was confirmed by spectroscopic tools, for instance, the
?
mass spectra showed [M ] at 323 (1.0 %).
˙
where dc surface pressure in mN/m. C surfactant concen-
tration. (dc/d logC)T is the slope of a plot of surface tension
versus concentration curves below CMC at constant
temperature.
Condensation of compound 1 with p-chlorobenzalde-
hyde produced a Schiff’s base, namely, (4-chloro-benzyl-
idene)-(5-heptadecyl-[1,3,4]oxadiazol-2-yl)-amine (2), while
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Scheme 1 Synthetic routes of compounds 1–12 and surfactants I–IX
(i) p-Chlorobenzaldehyde, ethanol, piperidine, reflux 6 h; (ii) acetic
anhydride, reflux 3 h; (iii) Cl–CH2COOEt, EtOH, reflux 8 h; (iv) Cl–
CH2COOH, benzene, piperidine, reflux 7 h; (v) benzene, pyridine,
reflux 5 h/or fusion in oil-bath for 2 h; (vi) AcOH, AcONa, reflux 5 h/
or fusion for 2 h in oil-bath; (vii) P2S5, dry xylene, reflux till orange
color; (viii) NH2OH.HCl, pyridine, reflux 4–5 h.; (ix) N2H4ꢀH2O,
benzene, reflux 6 h; (x) N2H4ꢀH2O, EtOH, reflux 5–6 h; (xi) n = 3, 5
and 7 mol of propylene oxide (P.O.)
?
?
˙
˙
acetylation of compound 1 with Ac2O produced N-(5-
heptadecyl[1,3,4]oxadiazol-2-yl)acetamide (3).
spectrum showed [M ] and [M ]?1 at 363 (0.68 %) and
364 (0.81 %), respectively.
Reaction of 2-amino oxadiazole 1 with ethyl chloro-
acetate in refluxing ethanol and with chloroacetic acid in
benzene in the presence of catalytic amount of piperi-
dine, produced 2-chloro-N-(5-heptadecyl[1,3,4]oxadiazol-
2-yl)acetamide (4) and 2-[(5-heptadecy[1,3,4]-oxadiazol-2-
yl) amino]acetic acid (5), respectively.
Cyclization of compound 5 using sodium acetate
in acetic acid afforded 2-heptadecyl- imidazo[2,1-
b][1,3,4]oxadiazol-5(6H)-one (7). The formation of 7
was evident from its IR which lacked any bands for the
carboxy hydroxyl group, and showed the expected mC=O
of unconjugated cyclic five membered ketone at
1
Furthermore, in order to increase the utility of oxadiaz-
oles, compounds 4 and 5 were subjected to cyclization. Thus,
cyclization of compound 4 either by fusion or refluxing in
benzene in the presence of pyridine produced 2-heptadecy-
limidazo[2,1-b][1,3,4]oxadiazol-6(5H)-one (6); the forma-
tion of which was confirmed by spectroscopic analysis. IR of
compound 6 lacked any mNH but showed mC=O of a-b
unsaturated five-membered ketone at 1,674 cm-1. The mass
1,681 cm-1. H NMR showed singlet band at 2.88 ppm
for cyclic CH2 moiety which supported the proposed
structure.
Substitution of the oxygen atom of oxadiazoles by a sulfur
or nitrogen atom represents a vital route to obtain thiadiazole
or triazole derivatives, respectively. Thus, when oxadiazole
1 was allowed to react with P2S5 in refluxing xylene,
2-amino-5-heptadecyl[1,3,4]-thiadiazole (8) was obtained.
123

J Surfact Deterg (2014) 17:509–523
515
Scheme 2 Proposed
mechanism for the formation of
compounds 11 and 12
The synthesis of compound 8 was previously achieved by the
reaction of thiosemicarbazide and stearic acid [38].
method [18–21] against Gram-negative bacteria, namely,
Escherichia coli, Gram-positive bacteria Staphylococcus
aureus and fungi namely, Aspergillus flavus and Candida
albicans. Tetracycline and Amphotericin B were taken as
positive references for antibacterial and antifungal agents,
respectively. The antimicrobial activity A of a tested
compound is determined at its minimum inhibitory con-
centration (MIC), i.e. at the lowest concentration of the
compound that completely inhibited visible growth of a
specific microorganism.
On the other hand, reaction of 1 with hydroxylamine
hydrochloride in pyridine afforded 3-amino-5-heptade-
cyl[1,2,4]triazol-4-ol (9). Similarly, oxadiazole 1 reacted
with hydrazine hydrate in refluxing benzene to give
5-heptadecyl [1,2,4]triazole 3,4-diamine (10).
Contrary to what was expected, carrying out the reaction
in boiling ethanol afforded two different compounds, none of
them being the expected triazole 10. These compounds were
identified as 6-heptadecyl[1,2,4]triazolo[3,4-b][1,3,4]oxa-
diazol-3-amine (11) and ethyl-N-[amino(hydrazinylid-
ene)methyl]heptadecylhydrazonoate (12). The mechanism
proposed to account for the formation of 11 and 12 involved
an initial nucleophilic attack of ethanol on the oxadiazole
nucleus followed either by cycloelimination [path a] with the
subsequent 1,3-dipolar cycloaddition of intermediate (I) to 1
leading to the formation of the thermodynamically more
stable triazole 11 rather than 5-heptadecyl[1,2,3]triazol-
o[5,1-b][1,3,4]oxadiazol-3-amine (13); or by ring opening
[path b] with the subsequent reaction with hydrazine to
produce (12) (Scheme 2). The formation of the isomeric
triazole (13) is ruled out since its formation necessitates 1,3-
dipolar cycloaddition of intermediate (I) with inverse electron
demand (Scheme 2), in addition, ab initio calculations at the
RHF/6-31G level indicated that the triazole 11 is more stable
than 13 by 22.24 kcal/mol. The structure of both compounds
was confirmed by spectroscopic analysis. Similar heterolytic
addition of low molecular weight alcohols to the C=N of oxa-
diazole has been reported for the photochemical reaction of
2-phenyl- and 2,5-diphenyl-1,3,4-oxadiazoles [39, 40].
As outlined in Table 1, the synthesized compounds
show varying degrees of inhibition against the tested
microorganisms. Thus, while 5-heptadecyl-[1, 3, 4]oxadi-
azole derivatives (1–5), 2-amino-5-heptadecyl[1,3,4]-thia-
diazole (8), 5-heptadecyl-[1,3,4]triazole derivative (9), and
hydrazinylidene hydrazonoate derivative (12) are inactive
toward the tested fungi, they have exhibited moderate
activity against both bacteria strains. On the other hand,
imidazo[2, 1-b][1,3,4]oxadiazolone derivatives (6,7) exhi-
bit moderate to high activity towards the tested bacteria
strains and exhibit good antifungal activity against Asper-
gillus flavus, while, 5-heptadecyl [1,2,4]triazole 3, 4-dia-
mine (10) reveals good activity toward both bacteria strains
and exhibits moderate antifungal activity against Candida
albicans. Triazolo[3,4-b][1,3,4]oxadiazole (11) is consid-
ered to be the most active compound in this series since it
shows good to very good activity against both bacterial and
fungal strains. These results are in agreement with previ-
ously reported results for oxadiazole, oxathiazole and tri-
azoles derivatives [41–44].
Nonionic Surfactants from Some Synthesized
Compounds
Antimicrobial Activities of the Synthesized Oxadiazole
Derivatives
Propoxylation of some of the new compounds (1, 3, 4, 5 and
8–12) with various quantities of propylene oxide (3, 5, and
7 mol) produced nonionic surfactants I(a–c)- IX(a–c), the
All the synthesized compounds (1–12) were screened
in vitro (using a modified Kirby-Bauer disc diffusion
123

516
J Surfact Deterg (2014) 17:509–523
structure of which was confirmed via IR and 1H-NMR
spectra. Thus, in addition to the original bands reported for
these compounds, IR spectrum showed a broad band in the
region (3,500–2,500) cm-1 (tOH) and two other bands in
the region (1,100–1,000) and (950–900) cm-1 for (tC–O–C
ether linkage of polypropoxy chain). The 1H-NMR spectrum
showed the protons of the propyleneoxy groups which appear
as broad multiple signals in the region (3.2–3.7) ppm. The
physical properties of these compounds are shown in Table 2.
surfactant molecules dissolve in water, they orientate
themselves in-between the water molecules and weaken the
hydrogen bond between them. This in turn decreases the
holding forces and lowers the surface and interfacial tension.
The extent by which the surfactant decreases the surface
tension depends on two competing forces. These are the
repulsion forces between water molecules and the hydro-
phobic part of the surfactant; and the attraction forces
between water molecules and the hydrophilic part of the
surfactant molecules. In the case at hand, the hydrophobic
part (heptadecyl side chain) is constant, while the hydro-
philic part changes as the number of the propylene oxide
units changes. Consequently, for a certain molecule, at a
certain concentration, while the abovementioned repulsive
force is unchanged, increasing the number of propylene
oxide units increases the attractive forces. As a consequence
and in accordance with the previously reported results [46],
the surface and interfacial tensions of the solution increases
by increasing the number of propylene oxide units
(n) included in the molecule, Table 3a. In addition, com-
paring structurally related surfactants I(a–c) and V(a–c)–VI
I(a–c) indicated that, at a certain (n) thiadiazole derivative
V(a–c) is slightly more effective in decreasing the surface
tension than oxadiazole I(a–c) and triazole derivatives
VII(a–c) and VI I(a–c). Within the oxadiazole derivatives
I(a–c)–IV(a–c), surfactants III(a–c) induce the highest
reduction in surface and interfacial tensions.
Surface Active Properties
The surface active properties of the prepared propoxylated
compounds I(a–c) to IX(a–c) were measured in a neutral
medium. The data obtained are outlined in Table 3a, b.
Surface and Interfacial Tensions
Surfactants are used in a large number of applications due to
their ability to alter the energy relationships at interfaces and
to lower the surface and interfacial tension [45]. As
Table 2 Physicochemical properties of the synthesized surfactants
Compd.
M. F.
M.wt
Color
Shape
Ia
C28H55N3O4
497
613
729
539
655
771
573
689
805
555
671
787
513
629
745
512
628
744
511
627
743
537
653
769
557
673
789
Yellow
Semi-solid
Semi-solid
Semi-solid
Powder
Ib
C34H67N3O6
C40H79N3O8
C30H57N3O5
C36H69N3O7
C42H81N3O9
C30H56N3O5Cl
C36H68N3O7Cl
C42H80N3O9Cl
C30H57N3O6
C36H69N3O8
C42H81N3O10
C28H55N3O3S
C34H67N3O5S
C40H79N3O7S
C28H56N4O4
C34H68N4O6
C40H80N4O8
C28H57N5O3
C34H69N5O5
C40H81N5O7
C29H55N5O4
C35H67N5O6
C41H79N5O8
C30H63N5O4
C36H75N5O6
C42H87N5O8
Yellow
Ic
Yellow
IIa
Black
Cloud Point
IIb
Black
Powder
IIc
Black
Powder
For nonionic surfactants, a common and characteristic
observation is that they exhibit a reverse solubility versus
temperature behavior in water, consequently their solutions
tend to become visibly turbid at a well-defined temperature.
This is known as the cloud point, above which the surfactant
solution phase separates into two phases. The cloud point is a
critical factor in the performance of nonionic surfactants;
generally, nonionic surfactants show optimal effectiveness
when used near or below their cloud point. In addition,
knowing the cloud point helps us to determine the storage
stability since storing at temperatures significantly higher
than the cloud point may result in phase separation and
instability. The cloud point depends on the chemical struc-
ture [47, 48]. For a given hydrophobic group the cloud point
is found to increase with increasing the length of the
hydrophilic moiety [49, 50]. As outlined in Table 3a, the
cloud point for the synthesized surfactants increases by
increasing the number of propylene oxide groups.
IIIa
IIIb
IIIc
IVa
IVb
IVc
Va
Brown
Semi-solid
Semi-solid
Semi-solid
Semi-solid
Semi-solid
Semi-solid
Powder
Brown
Brown
Dark-gray
Dark-gray
Dark-gray
Pale-yellow
Pale-yellow
Pale-yellow
Dark-green
Dark-green
Dark-green
Brown
Vb
Powder
Vc
Powder
VIa
VIb
VIc
VIIa
VIIb
VIIc
VIIIa
VIIIb
VIIIc
IXa
IXb
IXc
Semi-solid
Semi-solid
Semi-solid
Semi-solid
Semi-solid
Semi-solid
Powder
Brown
Brown
White
White
Powder
White
Powder
Wetting Time
Yellow
Semi-solid
Semi-solid
Semi-solid
Yellow
The degree of wetting is the resultant of two competing
forces. These are, adhesive forces between a liquid and
Yellow
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517
Table 3 Surface properties of some synthesized surfactants
Compd.
No. of
molesa
Surface tension
(mN/m) 0.1 wt%
Interfacial tension
(mN/m) 0.1 wt%
Cloud point
(°C) 1.0 wt%
Wetting time
(s) 0.1 wt%
Foam height
(mm) 1.0 wt%
Emulsion stability
(min) 20 mol
(a)
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
33
35
38
34
36
39
29
30
33
31
33
36
31
32
34
34
36
37
37
41
43
30
31
33
33
34
36
10
13
15
9
86
93
52
47
42
50
47
48
44
39
38
53
48
45
50
46
40
54
50
46
52
48
45
50
48
46
43
40
38
70
80
45
43
40
44
42
38
49
46
42
52
49
44
44
42
38
42
38
36
55
52
46
52
49
44
46
43
40
[100
82
100
50
II(a–c)
12
13
8
98
70
[100
81
90
III(a–c)
IV(a–c)
V(a–c)
90
10
13
11
14
16
10
12
14
12
14
16
13
15
16
11
13
15
10
12
13
95
100
120
100
120
150
60
[100
86
94
[100
85
90
80
[100
86
100
90
VI(a–c)
VII(a–c)
VIII(a–c)
IX(a–c)
95
110
120
90
[100
89
97
100
120
100
120
150
90
[100
88
96
[100
82
91
110
120
[100
2
Amin (A /mol)
No. of molesa
CMC (mmol/L)
cCMC (mN/m)
pCMC mN/m
PC20 (mmol/L)
Cmax (mol/cm2)
˚
Compd.
(b)
I(a–c)
3
5
7
3
5
7
3
5
7
3
5
7
3
5
7
3
5
7
3
5
7
5.0
34
38
2.30
2.11
2.00
2.00
1.92
1.70
2.51
2.41
2.27
3.19
3.02
2.72
2.40
2.25
2.05
2.70
2.35
1.96
1.85
1.23
1.09
0.99
1.89
2.27
0.95
1.82
2.19
0.84
1.62
1.97
0.98
1.88
2.26
0.80
1.55
1.89
0.97
1.85
2.23
1.14
2.15
2.57
1.66
0.88
0.73
1.73
0.91
0.75
1.97
1.02
0.84
1.65
0.87
0.72
2.06
1.07
0.87
1.70
0.89
0.74
1.44
0.77
0.64
7.8
37
35
10.0
10.0
12.0
19.9
3.1
39
33
II(a–c)
III(a–c)
IV(a–c)
V(a–c)
34.5
37.5
39
37.5
34.5
33
29
43
3.9
31
41
5.4
34
38
0.64
0.95
1.9
32
40
35.5
38
36.5
34
4.0
31
41
5.6
33
39
9.0
35
37
VI(a–c)
VII(a–c)
2.0
35
37
4.5
36.5
39
35.5
33
11.0
14.0
59.0
81.0
38
34
42
30
45
27
123

518
J Surfact Deterg (2014) 17:509–523
Table 3 continued
2
Amin (A /mol)
No. of molesa
CMC (mmol/L)
cCMC (mN/m)
pCMC mN/m
PC20 (mmol/L)
Cmax (mol/cm2)
˚
Compd.
VIII(a–c)
3
5
7
3
5
7
3.8
5.1
6.0
5.3
7.7
10.7
30
33
34
34
35
38
42
39
38
38
37
34
2.42
2.29
2.22
2.28
2.11
1.97
0.79
1.59
1.89
0.98
1.87
2.25
2.05
1.09
0.87
1.68
0.88
0.73
IX(a–c)
a
Number of propylene oxide units
solid that causes a liquid drop to spread across the surface;
and cohesive forces within the liquid which causes the drop
to ball up and avoid contact with the surface. Addition of
surfactants to water lowers the surface and interfacial
tension; this in turn lowers the contact angle between the
liquid–vapor interface and the solid–liquid interface;
resulting in more surface wetting. Consequently, surfac-
tants are commonly used as wetting agents. In the present
work, the efficiency of the synthesized surfactants as wet-
ting agents was measured in terms of wetting time
Table 4 Resistance of the synthesized surfactants towards acidic and alkaline hydrolysis
Compd
Surface tension
(mN/m) 0.1 wt
Surface tension of 0.1 % surfactant (stability to hydrolysis)
H2SO4 (5 %) 25 °C
After boiling (5 %)H2SO4
NaOH (1 %) 25 °C
After boiling (1 %NaOH)
30 min
60 min
30 min
60 min
Ia
33
35
38
34
36
39
29
30
33
31
33
36
31
32
34
34
36
37
37
41
43
30
31
33
33
34
36
34
36
38
35
37
39
30
31
34
32
35
37
33
34
36
35
36
39
39
41
44
31
32
33
34
35
38
34
37
39
36
37
39
31
33
34
33
36
38
33
34
36
35
37
40
40
43
46
33
32
34
36
36
41
36
40
40
38
38
42
34
34
36
34
36
40
36
35
38
37
40
41
43
44
46
34
34
37
37
39
42
33
36
38
34
37
39
29
30
33
31
33
37
32
32
34
34
37
38
37
41
43
30
32
34
33
34
37
34
36
38
35
37
40
30
30
33
31
34
37
32
33
35
34
37
38
38
41
44
30
33
35
33
35
37
34
37
38
35
37
40
30
31
34
31
34
38
33
33
35
35
37
39
38
42
44
31
33
35
34
35
37
Ib
Ic
IIa
IIb
IIc
IIIa
IIIb
IIIc
IVa
IVb
IVc
Va
Vb
Vc
VIa
VIb
VIc
VIIa
VIIb
VIIc
VIIIa
VIIIb
VIIIc
IXa
IXb
IXc
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J Surfact Deterg (2014) 17:509–523
519
according to Draves technique [28], which measures the
ability of a surfactant solution to displace air from a
weighted skein of cotton by spreading wetting. Shorter
wetting times indicate more efficient wetting. Surfactants
I(a–c) to IX(a–c) demonstrate varying wetting abilities
depending on the number of propylene oxide units
emulsion [53, 54]. Generally, the measured time ranged
between 36 and 55 min, thus, indicating moderate
emulsifying properties for the synthesized surfactants.
CMC Measurements
(n) (Table 3a). For
a
given surfactant, increasing
The CMC measures the efficiency of surfactants, it
indicates the amount of surfactant required to reach
maximum surface tension reduction. A surfactant having
a low CMC value enjoys excellent wetting, emulsifying,
solubilizing and detergency properties. Within a given
series of structurally related surfactants, factors that lead
to a decrease in the surface tension are expected to
decrease the CMC value. As outlined in Table 3a, b, the
surface tension, CMC values and the surface tension at
the critical micelle concentration (cCMC) measured for
I(a–c)–IX(a–c) increase as the propylene oxide units
increases. Within each series of surfactants, noting that
the hydrophobic part is unchanged, the smallest CMC
value is reached where n = 3, i.e., when the adhesive
force is at its least (Graphs of surface tension vs log of
concentration of added surfactant, used in the determi-
nation of the CMC are presented in the supplementary
material section). Previous reports agree with our results
[55].
(n) increases the adhesive forces relative to the cohesive
forces [51] with the concomitant decrease of wetting time.
Surfactants IIIc and IXc exhibited the shortest sinking
time, consequently, are the most efficient wetting agents
among the studied group. This may be attributed to the
increase in the adhesive forces due to the presence of
chlorine atom and ethoxy group in III and IX, respectively.
Foaming Properties
Foam consists of gas covered with thin liquid film. It is
thermodynamically unstable and tends to collapse to liquid
which is the lowest energy state. In solution, the presence
of a surfactant lowers the surface tension and eases foam
generation with simultaneous adsorption of the surfactant
molecules onto the interface between gas and liquid. The
adsorption of surfactant molecules at the foam walls
opposes their collapse. The foamability of the synthesized
surfactant was examined using the Ross Miles method [29].
As indicated in Table 3a, and in agreement with previous
reports [51–53], the foam height of the synthesized sur-
factants increases by increasing the propylene oxide units
per molecule of surfactant. These results suggest that
increasing the adhesive forces—brought upon by increas-
ing (n)- draws more surfactant to the interface which in
turn enhances the formation of foam.
Effectiveness (pCMC
)
The effectiveness of a surfactant (p) is measured by its
ability to induce the maximum reduction in the surface
tension. Since the CMC point presents the minimum
surfactant concentration needed to produce the maximum
reduction in surface tension; consequently, the effec-
tiveness of a surfactant (pCMC) can be measured from
the decrease in the surface tension of pure water (c0) that
is induced by this surfactant at the CMC [32]. Logically,
effectiveness of the prepared surfactants decreases as
(cCMC) increases, Table 3b.
Emulsion Stability
Emulsification is an important property of surfactants
that broadens their applications. For instance, tiny frag-
ments of oil suspended in pure water will spontaneously
assemble themselves into much larger masses. In the
presence of an appropriate surfactant, the interfacial
tension between the two immiscible liquids is reduced to
a sufficiently low value, thus, emulsification takes place
and permits stability of minute droplets of oil in the bulk
of water (or vice versa). The emulsifying power of the
prepared surfactants in terms of time needed for the
separation of 9 mL of the solution is presented in
Table 3a. In accordance with the interfacial tension
measurements (vide supra), the data show that, the sta-
bility of the formed emulsion decreases as the number of
propylene oxide units increases. Obviously, the solubility
of the surfactant in the oil phase decreases as the
hydrophilic part (n) increases, resulting in weaker
Efficiency (PC20)
In solution, surfactants lower the surface tension due to
their adsorption in between water molecules. Thus, the
performance of a surfactant can also be discussed in
terms of its efficiency of adsorption. This is usually
defined as the surfactant adsorption efficiency, which is
the concentration of a surfactant required to produce a
20 mN/m reduction in surface tension. It is designated
by PC20 and can be calculated by Eq. 2 (vide supra)
[33]. The larger PC20 the more efficiently the surfactant
is adsorbed at the interface and the more efficiently it
reduces surface tension. In accordance of the above
mentioned results, values of PC20 for the prepared
123

520
J Surfact Deterg (2014) 17:509–523
surfactants are found to decrease by increasing the
number of propylene oxide units (cf Table 3a, b).
increased by increasing the number of propylene oxide
units and ranged between 0.79 and 2.57 mol/cm2.
Maximum Surface Excess Cmax
Minimum Surface Area (Amin)
The extent of surfactant adsorption at a liquid surface is
expressed in terms of its surface excess concentration,
C. This is defined as the excess of surfactant present per
unit area of surface over what would be present if
uniform surfactant concentration existed right up to the
surface. Surface excess concentration Cmax, is related to
surface tension by the Gibbs equation, Eq. 3 [33] and
to its maximum surface concentration CMC, and
efficiency by the following equation (Eq. 6) by Rosen
[56].
The area per surfactant molecule Amin at the air/water
interface at surface saturation provides information about
the degree of packing and the orientation of the adsorbed
surfactant molecule [35, 36]. The calculated average areas
Amin are given in Table 3b. Within a series of surfactants,
increasing the number of propylene oxide units results in a
significant decrease in Amin. This indicates that higher
order of packing is induced upon increasing (n).
Resistance to Hydrolysis
ꢃ
ꢄ
CCMC
pCMC ¼ 20 þ 2:303nRTCmax log
ð6Þ
Surfactants are intensively used in the manufacture of
detergents, consequently, the stability of a certain surfactant
towards acids and bases is a crucial factor in its utilization.
Table 4 presents the results obtained from testing the
Cp ꢁ 20
The data obtained from applying Eq. 3 are presented in
Table 3b. It indicated that the maximum surface excess
Table 5 Biodegradability of the synthesized surfactants
Compd.
No. of molesa
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
63
55
47
51
46
41
49
46
41
53
49
46
53
48
45
56
53
51
50
46
41
51
46
42
54
51
47
67
64
58
62
54
52
58
51
52
69
62
55
66
60
50
68
62
60
60
54
52
62
55
54
61
60
58
75
69
66
77
68
65
67
58
56
74
67
57
75
68
62
79
69
66
77
68
65
78
69
66
73
77
66
84
80
77
84
71
67
75
69
67
83
78
66
85
78
74
86
85
84
84
71
67
86
73
69
81
84
78
92
88
45
94
84
81
82
76
72
97
85
76
95
91
83
96
94
93
94
84
80
93
85
80
90
91
85
–
–
–
–
–
–
–
–
–
91
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
91
94
–
II(a–c)
III(a–c)
IV(a–c)
V (a–c)
VI(a–c)
VII(a–c)
VIII(a–c)
IX(a–c)
a
91
88
87
84
83
–
92
89
–
–
93
–
–
–
–
95
93
–
91
90
–
–
92
Number of propylene oxide units
123

J Surfact Deterg (2014) 17:509–523
521
resistance of the synthesized surfactants towards acidic and
alkaline hydrolysis. In an acidic medium, compounds I(a–c)
to IX(a–c) show high stability when boiled for 30 min, but
they are less stable upon boiling for 60 min. On the other
hand, in an alkaline medium, the synthesized surfactants are
only slightly affected even after boiling for 60 min. There-
fore, we concluded that, it would be safe to use the synthe-
sized surfactants in the manufacture of detergents.
consequence, the synthesized compounds and surfactants
are safe for human beings as well as the environment. They
can be used in the manufacture of drugs, cosmetics, mod-
erate emulsifiers, wetting agents, textiles and dyes.
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position of full professor in organic chemistry at the Faculty of
Science, Benha University. Her research interests relate to the
synthesis of heterocyclic compounds of biological interest and using
fatty acids to synthesize heterocycles having surface and biological
properties.
properties of aryl alkyl surfactant solution. J Surf Deterg
9:245–248
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surfactants. Biodegradability of surfactants. Springer, The Neth-
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Amal A. Mahmoud is currently a professor of organic chemistry at
the Faculty of Science at Benha University, Egypt. She received her
M.Sc. and Ph.D. degrees from Zagazig University. Her research
interests relate to organic synthesis and polymeric surfactants having
heterocyclic moiety.
Author Biographies
Alaa S. Gouda is an associate lecturer at the department of Chemistry
in the Faculty of Science at Benha University, Egypt. He received his
B.Sc. in 2006 and M.Sc. in 2010 from the same university. His
research interests relate to the synthesis of heterocyclic compounds of
biological interest and using fatty acids for synthesizing heterocycles
having surface and biological activities.
Iman A. Gad El-Karim received her Ph.D. in organic chemistry
from the Imperial College of Science and Technology—London
University. Currently, she is an assistant professor of organic
chemistry at the Faculty of Science, Benha University, Egypt. Her
research interests relate to the synthesis of novel organic compounds
having biological activities, novel surfactants and theoretical organic
chemistry.
Mahasen S. Amine graduated from Ain Shams University, Egypt in
1973. She received her M.Sc. and Ph.D. degrees in 1983 and 1988
respectively from Ain Shams University. Since 1998 she has held the
123