Substituted thiadiazole, oxadiazole, triazole and triazinone as antimicrobial and surface activity compounds

Article abstract of DOI:10.1007/s11743-012-1368-6

Stearic acid (1) was utilized as a new cheap starting material in the manufacture of important biologically active heterocycles as thiadiazole, oxadiazole, triazole and triazinone derivatives (2-11) by treating with different nucleophiles. These heterocycles bears active hydrogen atom (SH, NH and NH₂) which could be propoxylated by different moles of propylene oxide (5, 10, 15 mol) to produce nonionic compounds (12-21)a-c having functions as surface and antimicrobial activities. The structural elucidation of these compounds is based on IR, ¹H NMR, ¹³C NMR and elemental analysis. The surface properties (surface and interfacial tension, cloud point, witting time, foaming properties and emulsion stability) and the biodegradability were screened beside these compounds have been tested for their antimicrobial activity. Graphical Abstract: Stearic acid 1 was utilized as a new cheap starting material in the manufacture of important biologically active heterocycles as thiadiazole, oxadiazole, triazole and triazinone derivatives by treating with different nucleophile at different reaction conditions.[Figure not available: see fulltext.]

Full text of DOI:10.1007/s11743-012-1368-6

J Surfact Deterg
DOI 10.1007/s11743-012-1368-6
ORIGINAL ARTICLE
Substituted Thiadiazole, Oxadiazole, Triazole and Triazinone
as Antimicrobial and Surface Activity Compounds
R. El-Sayed
Received: 15 November 2011 / Accepted: 16 May 2012
Ó AOCS 2012
Abstract Stearic acid (1) was utilized as a new cheap
starting material in the manufacture of important biologi-
cally active heterocycles as thiadiazole, oxadiazole, triazole
and triazinone derivatives (2–11) by treating with different
nucleophiles. These heterocycles bears active hydrogen
atom (SH, NH and NH2) which could be propoxylated by
different moles of propylene oxide (5, 10, 15 mol) to pro-
duce nonionic compounds (12–21)a–c having functions as
surface and antimicrobial activities. The structural eluci-
transformations starting from easily available fatty com-
pounds. Many fatty acids and their derivatives are known
for their antimicrobial [2] and antifungal activities [3].
Fatty acid hydrazide is an important starting material for a
wide range of derivatives used as pharmaceutical products
and surfactants [4]. The synthesis of interesting heterocy-
cles, such as 1,3,4-oxadiazoles are used as biologically
active compounds in medical science and agriculture [5].
Various 1,3,4-oxadiazoles show herbicidal effects, espe-
cially against broad leafed weeds and grasses in crops such
as rice and corn [6]. Also, 1,3,4-thiadiazoles were reported
as highly anti-inflammatory [7], anti-microbial [8], pesti-
cidal [9], antiparasitic property [10], anticancer [11], anti-
convulsant agents [12–14]. We were interested in the
synthesis of triazole, oxazole, thiadiazole, oxadiazole and
further N and O/S-containing heterocyclic fatty acid
derivatives in order to enlarge the variety of interesting
fatty compounds and to open up a new potential for
renewable raw materials as possible biologically active
compounds. In view of the above mentioned facts and in
continuation of our work on the syntheses of biologically
important heterocyclic compounds [15–18]. It was inter-
esting to prepare some biologically active heterocycles
(triazole, thiadiazole and oxadiazole) which constitute an
important class of organic compounds with diverse bio-
logical activities.
1
dation of these compounds is based on IR, H NMR, 13C
NMR and elemental analysis. The surface properties (sur-
face and interfacial tension, cloud point, witting time,
foaming properties and emulsion stability) and the biode-
gradability were screened beside these compounds have
been tested for their antimicrobial activity.
Keywords Synthesis Á Thiadiazole Á Oxadiazole Á
Triazole Á Antimicrobial and surface activities
Introduction
Our work on the synthesis of heterocyclic fatty compounds
is closely related to Sharpless’s click chemistry. Our idea
was to achieve access to pharmacologically interesting
compounds based on renewable raw materials that serve
as important feedstocks for the chemical industry with
regard to a sustainable development [1] through simple
Experimental Protocols
All melting points are uncorrected and determined by the
open capillary method using a Gallenkamp melting point
apparatus. IR spectra (KBr disk) of the synthesized com-
pounds were recorded on an FT/IR-BRUKER, Vector 22
(Germany), JASCO FT/IR-4100 (Japan), and JASCO FT/
R. El-Sayed (&)
Chemistry Department, College of Applied Sciences,
Umm Al-Qura University, PB 7296, P.O.: 712,
Makkah 21955, Saudi Arabia
e-mail: ref_at@hotmail.com
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J Surfact Deterg
IR-460? (Japan). 1H- and 13C-NMR spectra were recorded
in deuterated chloroform (CDCl3) or dimethyl sulfoxide
(DMSO-d6) as a solvent on a Varian Mercury VXR-300
clear solution, a solution of I2/KI was added till permanent
tinge of iodine persisted at room temperature. The mixture
was immediately refluxed and more I2/KI was added till a
permanent tinge was obtained. The mixture was then
cooled and poured into ice-cold water; the solid that sep-
arated was collected by filtration, washed with water and
with dilute thiosulfate solution and again with water. The
solid was dried and recrystallized from ethanol to give 4
(1.25 g; 62 %), mp 65–67 °C.; IR: 3,316, 3,144 (NH2),
1
spectrometer (300 MHz for H NMR and 75 MHz for 13C
NMR) using TMS as internal reference and chemical shifts
are expressed in d (ppm). All the synthesized compounds
gave satisfactory elemental analyses. Surface active prop-
erties were carried out at the Chemistry Department of the
Faculty of Applied Science, Umm Al-Qura University,
Saudi Arabia. Antibacterial and antifungal activity was
carried out in Micro Analytical Center, Faculty of Science,
Cairo University, Egypt.
1
1,612 (C=N), 1,166 and 715 (oxadiazole ring) cm-1. H
NMR (CDCl3): d 0.89 (t, 3H, terminal CH3), 1.24–2.15
(m, 32H, CH aliphatic), 6.67 (s, 2H, NH2 which disap-
peared on addition of D2O). 13C NMR (CDCl3): d 14.15,
20.95, 22.70, 24.12, 24.84, 25.57, 29.16, 29.37, 29.44, 29.47,
29.51, 29.59, 29.63, 29.66, 29.67, 29.70, 31.92, 153.48,
178.64. Anal. Calc. for C19H37N3O (323.52): C, 70.54; H,
11.53; N, 12.99. Found C, 70.51; H, 11.50; N, 12.96.
2-Stearoylhydrazinecarbothioamide (2)
A solution of stearic acid hydrazide 1 (2 g, 0.05 mol) in
ethanol (50 mL) to which mixed potassium thiocyanate
(0.1 mol) and hydrochloric acid 3 mL were added with
constant stirring for 2 h, the mixture was immediately
evaporated to dryness on a steam bath. On cooling, the
separated solid was filtered, washed with cold water, dried
and recrystallized from ethanol as white needles. (1.37 g;
73 %), mp 122–124 °C.; IR: 3,433, 3,279, 3,134 for pri-
mary and secondary amino group, 2,919, 2,850 (CH ali-
5-Heptadecyl-1,3,4-thiadiazol-2-amine (5)
Sulfuric acid (98 %; 10 mL) was added to the thiosemi-
carbazide 2 (1.5 g, 0.05 mol), and the mixture was stirred
for 24 h at room temperature. The mixture was then poured
onto crushed ice (200 g), neutralized with concentrated
ammonium hydroxide solution and stirred for 20 min. The
separated crude product was filtered, washed with water,
dried and recrystallized from aqueous ethanol to afford 5
(079 g; 52 %), mp 108–110 °C.; IR: 3,319, 3,188 (NH2),
phatic), 1,696 (CO) and 1,290 (C=S) cm-1 1H NMR
.
(CDCl3): d 0.89 (t, 3H, terminal CH3), 1.24–2.15 (m, 32H,
CH aliphatic), 7.40 (s, 1H, CONHNH), 8.98 (s, 2H, NH2),
10.29 (s, 1H, CONH). Anal. calc. for C19H39N3OS
(357.60): C, 63.82; H, 10.99; N, 11.75; S, 8.97. Found C,
63.87; H, 11.04; N, 11.71; S, 9.02.
1
1,603 (C=N) cm-1. H NMR (CDCl3): d 0.88 (t, 3H, ter-
minal CH3), 1.25–2.59 (m, 32H, CH aliphatic), 7.82 (S,
2H, NH2 which disappeared on addition of D2O). Anal.
Calc. for C19H37N3S (339.58): C; 67.20, H; 10.98, N;
12.37, S; 9.44. Found: C; 66.91, H; 10.67, N; 12.18, S;
9.23.
3-Heptadecyl-1H-1,2,4-triazole-5(4H)-thione (3)
A solution of thiosemicarbazide 2 (3 g, 0.01 mol) in eth-
anol (15 mL) and potassium hydroxide (10 %, 10 mL) was
refluxed for 7–8 h on a steam bath. It was cooled and
acidified with dilute HCl. The resulting solid was filtered,
dried and recrystallized from ethanol to yield 3 (2.15 g;
71 %), mp 91–93 °C.; IR: 3,421, 3,196 (NH), 2,919, 2,849
5-Heptadecyl-1,3,4-thiadiazol-2(3H)-one (6)
Sodium nitrite solution (10 %; 10 mL) was added dropwise
to an ice cooled suspension of 5 (0.95 g, 0.01 mol) and
hydrochloric acid (5 mL) in cold water (20 mL), with
continuous stirring over a period of 20 min. The temper-
ature was then allowed to rise to room temperature and the
mixture was heated to boiling for 10 min, cooled and
allowed to stand overnight. The separated crude product
was filtered, washed with water, dried and recrystallized
from ethanol to yield 6 (0.55 g; 58 %), mp 65–67 °C.; IR:
1
(CH aliphatic), 1,617 (C=N), 1,309 (C=S) cm-1; H NMR
(CDCl3): d 0.86 (t, 3H, terminal CH3), 1.26–1.86 (m, 32H,
CH aliphatic), 10.97 (s, 1H, NH), 13.98 (s, 1H, NH). 13C
NMR (DMSO-d6): d 13.70, 16.57, 22.31, 25.25, 28.45,
28.47, 28.52, 28.53, 28.58, 28.75, 28.84, 28.88, 29.02,
29.09, 31.31, 33.68, 39.07, 154.79, 175.22. Anal. Calc. for
C19H37N3S (339.58): C, 67.20; H, 10.98; N, 12.37; S, 9.44.
Found C, 67.27; H, 11.01; N, 12.35; S, 9.40.
3,271 (NH), 1,684 (CO), 1,611 (C=N) cm-1 13C NMR
.
5-Heptadecyl-1,3,4-oxadiazol-2-amine (4)
(CDCl3): d 14.15, 25.25, 28.45, 28.47, 28.52, 28.53, 28.58,
28.75, 28.84, 28.88, 29.02, 29.04, 29.09, 31.31, 33.68,
39.07, 31.92, 154.74, 175.22. Anal. Calc. for C19H36N2OS
(340.57): C, 67.01; H, 10.65; N, 8.23; S, 9.42. Found C,
67.23; H, 10.75; N, 8.03; S, 9.22.
A solution of thiosemicarbazide 2 (1.4 g, 0.01 mol) in
ethanol (15 mL) was added to a solution of sodium
hydroxide (5 N, 5 mL) with cooling and stirring. To this
123

J Surfact Deterg
N-phenyl-2-stearoylhydrazinecarbothioamide (7)
(415.68): C, 72.24; H, 9.94; N, 10.11; S, 7.71. Found C,
72.41; H, 10.11; N, 10.18; S, 7.88.
Equimolar quantities (1.7 g, 0.01 mol) of acid hydrazide 1
and phenyl isothiocyanate (0.01 mol) were dissolved in
absolute ethanol (25 mL) in a round-bottom flask. The
solution was refluxed for 3 h on a water bath. The solution
was concentrated under reduced pressure and the solid
separated was collected and recrystallized from ethanol to
give 7 (1.2 g; 70 %), mp 139–141 °C.; IR: 3,396, 3,221
5-Heptadecyl-N3-phenyl-4H-1,2,4-triazole-3,4-diamine
(10)
A mixture of 7 (1.3 g, 0.005 mol) and hydrazine hydrate
(0.025 mol) was refluxed in ethanol (20 mL) for 3 h. The
reaction mixture was cooled and poured over crushed ice.
The solid separated was filtered and recrystallized from
ethanol/water to get 10 (0.85 g; 65 %), mp 118–120 °C.;
IR: 3,241, 3,160 (NH), 3,052 (CH aromatic), 1,601 (C=N)
1
(NH), 1,676 (CO), 1,209 (C=S) cm-1. H NMR (CDCl3):
d 0.86 (t, 3H, terminal CH3), 1.19–2.47 (m, 32H, CH ali-
phatic), 4.59 (s, 1H, NH which disappeared on addition of
D2O), 7.31–7.33 (m, 5H, ArH), 7.59 (S, 1H, NH), 11.36
(S, 1H, NH). Anal. Calc. for C25H43N3OS (433.69): C,
69.23; H, 9.99; N, 9.69; S, 7.39. Found C, 69.38; H, 10.05;
N, 9.49; S, 7.43 %.
1
cm-1. H NMR (CDCl3): d 0.87 (t, 3H, terminal CH3),
1.21–2.97 (m, 32H, CH aliphatic), 5.02 (s, 1H, NH2 which
disappeared on addition of D2O). 7.17–7.63 (m, 5H, ArH),
10.08 (s, 1H, NH). Anal. Calc. for C25H43N5 (413.64): C,
72.59; H, 10.48; N, 16.93. Found C, 72.72; H, 10.64; N,
17.15.
3-Heptadecyl-4-phenyl-1H-1,2,4-triazole-5(4H)-thione
(8)
3-Heptadecyl-1,2-dihydro-1,2,4-triazin-5(6H)-one (11)
A solution of 7 (1.2 g, 0.01 mol) in ethanol (15 mL) was
added to a solution of sodium hydroxide (5 N, 5 mL) with
cooling and stirring. The reaction mixture was refluxed for
6–8 h. After completion, the reaction mixture was allowed
to cool, filtered and acidified with hydrochloric acid (2 M).
The precipitate obtained was filtered washed with water
and dried and recrystallized from ethanol to obtain 8
(0.82 g; 68 %), mp 85–87 °C.; IR: 3,228 (NH), 3,043 (CH
Acid hydrazide 1 (1.6 g, 0.01 mol) and chloroacetamide
(0.41 g, 0.01 mol) were refluxed in DMF (30 mL) for
26–30 h. After the completion of the reaction (monitored
by TLC), the reaction mixture was concentrated, cooled
and poured into ice-cold water (100 g). The desired triaz-
inone which separated out was filtered and dried. Further
purification by column chromatography over silica gel
using a petroleum ether-diethyl ether mixture as the eluent
afforded 11 (1.2 g; 75 %), mp, 144–146 °C.; IR: 3,454,
aromatic), 1,601 (C=N), 1,186 (C=S) cm-1 1H NMR
.
(CDCl3): d 0.86 (t, 3H, terminal CH3), 1.23–2.76 (m, 32H,
CH aliphatic), 11.99 (s, 1H, NH which disappeared on
addition of D2O), 7.29–7.57 (m, 5H, ArH). 13C NMR
(CDCl3): d 13.75, 24.66, 28.37, 28.48, 28.58, 28.66, 28.74,
28.84, 28.86, 28.86, 28.89, 28.91, 28.96, 28.99, 29.07,
31.30, 33.65, 33.70, 39.08, 116.69, 121.22, 128.42, 129.47,
154.74, 173.10. Anal. Calc. for C25H41N3S (415.68): C,
72.24; H, 9.94; N, 10.11; S, 7.71. Found C, 72.33; H,
10.02; N, 10.25; S, 7.83.
3,231 (NH), 1,687 (CO), 1,566 (C=N) cm-1 1H NMR
.
(CDCl3): d 0.85 (t, 3H, terminal CH3), 1.24–1.65 (m, 32H,
CH aliphatic), 2.15 (s, 2H, CH2 of triazinone ring), 3.89
(s, 1H, NH2), 6.67 (s, 1H, NH which disappeared on addition
of D2O). Anal. Calc. for C20H39N3O (337.54): C, 71.17;
H, 11.65; N, 12.45. Found C, 71.25; H, 11.74; N, 12.28.
Preparation of Nonionic Surfactants
(12–21a–c) from the Synthesized Compounds (2–11)
5-Heptadecyl-N-phenyl-1,3,4-thiadiazol-2-amine (9)
The terms of nonionic surfactants refers chiefly to poly-
oxypropylene derivatives, they are usually prepared by the
addition of different moles (n) of propylene oxide (n & 5,
10, 15 mol) to synthesized products (2–11) at any active
hydrogen atoms (NH, NH2, SH) using KOH as the catalyst.
The processes were completed as described in [19]. The
accurate amount of propylene oxide taken up and average
degree of propenoxylation (n) was determined from the
increased mass of the reaction mixture and confirmed by
spectroscopy. The structures of the synthesized nonionic
A solution of 7 (0.95 g, 0.005 mol) was added portionwise
to (25 mL) of concentrated sulfuric acid at 0 °C with
continuous stirring. The reaction mixture was stirred fur-
ther for 3 h at room temperature and then allowed to stand
overnight. Neutralization with diluted sodium hydroxide
precipitated a crude solid, which was filtered, and washed
with water. The crude product was then recrystallized from
DMF to furnish 9 (0.51 g; 53 %), mp 89–91 °C.; IR: 3,221
(NH), 1,601 (C=N) cm-1. 1H NMR (CDCl3): d 0.95 (t, 3H,
terminal CH3), 1.43–2.96 (m, 32H, CH aliphatic),
6.50–7.08 (m, 5H, ArH), 8.01 (s, 1H, NH which disap-
peared on addition of D2O). Anal. Calc. for C25H41N3S
1
surfactants were confirmed via IR and H-NMR spectra.
All IR spectra after the addition of the propylene oxide,
showed, two broad bands at 1,070 and 960 cm-1
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J Surfact Deterg
Scheme 1 Synthesis of
thiadiazole, oxadiazole, triazole
and triazinone derivatives
n P.O
N
N
14a-c
13a-c
O
NH2
R
15a-c
4
n P.O
NaOH
I / KI
n P.O
O
S
N
NH
H2SO4
NH4OH
N
N
KOH
H H
R C N N C NH2
N
H
S
R
EtOH
S
NH2
R
R
2
n P.O
12a-c
16a-c
5
3
i) NaNO2
ii) H2O
KSCN / HCl
O
ClCH2CONH2
DMF
O
H
n P.O
N
NH
O
N
R C N NH2
NH
S
N
H
R
1
6
11
n P.O
PhSCN
21a-c
O
S
NH2NH2
NaOH
N
N
N
NH
H H
H
R C N N C N Ph
R
N
NHPh
R
N
S
7
n P.O
NH2
Ph
H2SO4
N
8
10
17a-c
n P.O
N
n P.O
R
S
NHPh
18a-c
20a-c
9
n P.O
R = C17H35
n = 5, 10, 15 moles of propylene oxide
19a-c
characteristic for the mC–O–C ether linkage of polypro-
penoxy chain, beside the original bands of the compound
and 1H-NMR spectra after the addition of propylene oxide,
showed, the protons of propenoxy group were assigned as a
broad multiple signals in the region (3.1–3.9) ppm, beside
the other protons of the compound.
various concentration of the synthesized surfactants
(0.05–10-6 mol/L) and at 25 °C [21].
Cloud Point
The cloud point, measure as inverse solubility character-
istic of nonionic surface active agents, was determined by
gradual heating 1.0 % wt solution in a controlled temper-
ature bath recording the temperature at which the clear or
nearly clear solutions become definitely turbid. Cooling the
solutions until they become clear again confirmed the
reproducibility of this temperature [22].
Biological Activity
Antimicrobial activity of the prepared compounds was
tested via a modification of the cup-plate method [20].
The Surface Active Properties
Wetting Time
Surface and Interfacial Tensions
The wetting powers of the tested surfactants were deter-
mined by immersing a sample of cotton fabric in 1.0 wt
aqueous solution of the surfactants and measuring the
sinking time in seconds [23].
Surface tension and interfacial tension were measured
using a Du Nouy tensiometer (KRUSS type 8451), at
123

J Surfact Deterg
CH3
tension. Surface tension measurements were made peri-
odically (each day) on each sample during the degradation
test [25] Biodegradation percent (D) for each sample was
calculated using the following relation. D = [(ct - c0)/
(cbt - c0)] 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).
n P.O
KOH
N
N
N
N
(CH2-CHO)xH
CH3
N
R
S
R
S
NH2
(CH2-CHO)yH
5
15a, n = 5
b, n = 10
c, n = 15
n = x + y
N
N
N
N
n P.O
KOH
CH3
Ph
(CH2-CHO)xH
R
N
N
R
N
NHPh
Chemistry
CH3
(CH2-CHO)yH
CH3
Hz(OCH-CH2)
N
NH2
Stearohydrazide (1) used as a starting material, was con-
veniently prepared from stearic acid following the previ-
ously reported method [26]. The behavior of 1 toward some
nitrogen nucleophiles was investigated. Thus, the reaction
of 1 with potassium thiocyanate in methanol and hydro-
chloric acid afforded thiosemicarbazide derivative 2. The
latter compound proved to be a useful key intermediate in
the synthesis of several heterocyclic nuclei. Thus, when 2
was refluxed with potassium hydroxide in ethanol yielded
3-heptadecyl-1H-1,2,4-triazole-5(4H)-thione (3). Treat-
ment of 2 with potassium iodide and iodine in the presence
of sodium hydroxide furnished 5-heptadecyl-1,3,4-oxa-
diazol-2-amine (4). Also, cyclization of 2 in the presence of
conc. H2SO4 produced 5-heptadecyl-1,3,4-thiadiazol-2-
amine (5) which was treated with sodium nitrite in the
presence of hydrochloric acid to give 5-heptadecyl-1,3,4-
thiadiazol-2(3H)-one (6) (Scheme 1).
10
20a, n = 5
b, n = 10
c, n = 15
R = C17H35
n = x + y + z
Scheme 2 Synthesis of nonionic surfactants
Foaming Properties
The foam production for 1.0 wt solution was measured by
the foam height initially produced [24].
Emulsion Stability
The emulsion was prepared from 10 mL of a 20 mmol/L
aqueous solution of surfactant and 5 mL of toluene at 40 °C.
The emulsifying properties was determined by the time it took
for an aqueous volume separating from the layer to reach
9 mL counting from the moment of the cession shaking [24].
On the other hand, the reactivity of 1 towards phenyl
isothiocyanate under different reaction conditions was
investigated. Thus, the reaction of 1 with phenyl isothio-
cyanate in dry benzene under reflux gave the thiosemicar-
bazide derivative 7 which was subjected to intermolecular
cyclization in alkaline medium (2 M NaOH) followed by
acidification with HCl to give 1,2,4-triazole derivative 8.
Biodegradability
Samples which were taken daily or more frequently were
filtered through filter paper before measuring the surface
Table 1 Antimicrobial activity of some synthesized compounds
Sample
Inhibition zone diameter (mm/mg sample)
E. coli (G?)
MIC (lg)
S. aureus (G?)
A. flavus (fungus)
C. albicans (fungus)
A (mm)
MIC (lg)
A (mm)
MIC (lg)
A (mm)
MIC (lg)
A (mm)
3
200
100
100
200
400
200
200
200
400
200
27
13
14
19
30
19
20
20
25
29
200
100
200
100
200
200
200
100
100
200
22
0.0
11
12
22
16
14
15
21
26
400
200
400
200
400
400
200
400
400
–
20
13
400
200
400
100
200
400
100
400
400
–
18
0.0
0.0
10
4
5
0.0
6
11
22
12
8
20
10
15b
19c
0.0
0.0
20b
12
15
–
13
14
–
21c
Gentamycin
A antimicrobial activity of tested compounds, MIC minimum inhibitory concentration, 0.0 not active, A [ 7 mm slightly active, A [ 15 mm
moderately active, A [ 20 mm highly active
123

J Surfact Deterg
Also, cyclization of 7 in the presence of conc. H2SO4 gave
thiadiazole derivative 9. Moreover, treatment of 7 with
hydrazine hydrate afforded 1,2,4-triazole derivative 10. Of
particular interest, a cyclocondensation reaction of 1 with
chloroacetamide in DMF under reflux conditions gave
3-heptadecyl-1,2-dihydro-1,2,4-triazine-5(6H)-one (11).
active agents due to their dual characters, one due to
conflict between the affinity of the hydrophobic and
hydrophilic structure shows surface active properties and
another one that is due to the heterocyclic moiety con-
firmed with aid of a hydrophilic moiety (propylene oxide)
give its biological activity. Propoxylation of the new
compounds (2–11) with various quantities of propylene
oxide (5, 10, and 15 mol) produced nonionic surfactants
(12–21)a–c, respectively. The surface active properties of
the prepared propoxylated compounds (12–21)a–c were
measured in a neutral medium by traditional procedures to
evaluate the possible utilization of these compounds in
Conversion of the Prepared Compounds (2–11)
to Nonionic Surfactants (12–21)a–c
The built up surfactant molecules containing a heterocyclic
moiety provide us with a most important class of surface
Table 2 Surface properties of synthesized compounds
Sample
n
Surface tension
(mN/m) 0.1 m/l
Interfacial tension
(mN/m) 0.1 m/l
Cloud point
(°C)
Wetting
time (s)
Emulsion
stability (min)
Foam height
(mm)
12a
12b
12c
13a
13b
13c
14a
14b
14c
15a
15b
15c
16a
16b
16c
17a
17b
17c
18a
18b
18c
19a
19b
19c
20a
20b
20c
21a
21b
21c
5
33
35
36
29
31
33
34
34
35
30
31
33
32
34
36
33
35
37
30
31
34
32
36
40
32
34
37
31
34
38
11.0
11.5
12.0
10.0
11.0
13.0
9.5
86
[100
[100
77
55
47
35
59
45
35
58
47
36
45
36
25
54
43
30
53
41
30
61
45
36
52
45
37
62
45
37
62
50
32
105
90
100
115
120
115
154
182
105
119
140
120
148
188
135
165
200
125
140
150
95
10
15
5
82
115
105
82
10
15
5
93
[100
79
113
98
10
15
5
10.5
12.0
10.0
10.5
12.0
9.5
87
89
80
63
100
92
10
15
5
85
96
63
87
96
10
15
5
9.5
95
88
10.5
11.0
11.5
11.5
8.0
[100
87
88
103
96
10
15
5
95
[100
80
85
119
111
97
10
15
5
9.5
87
120
160
130
170
185
125
150
175
128
178
200
11.5
9.0
98
77
85
10
15
5
10.5
12.0
10.0
11.5
13.0
10.5
12.0
14.0
87
75
91
70
77
95
10
15
5
87
90
[100
74
84
94
10
15
86
90
[100
86
Surface and interfacial tensions = 0.1 dyne/cm, cloud point = 1 °C, foam height = 2 mm, wetting time = 1 s, emulsion = 30 s,
n moles of propylene oxide
123

J Surfact Deterg
various industrial fields. Scheme (2) shows the propen-
oxylation of compounds 5 and 10 as examples. The
structures of the synthesized chemicals are listed in
(Table 4).
Table 3 Biodegradability of some selected of prepared surfactants
Sample 1st day 2nd day 3rd day 4th day 5th day 6th day
12a
12b
12c
15a
15b
15c
17a
17b
17c
19a
19b
19c
21a
21b
21c
40
39
40
40
40
38
44
42
42
40
39
39
41
40
40
57
53
49
55
49
45
57
51
46
53
49
45
55
53
50
69
62
60
66
58
55
65
58
56
64
58
55
66
62
58
79
76
73
77
74
67
79
74
70
79
68
64
77
72
68
88
85
81
90
88
87
93
88
80
88
79
74
89
86
83
96
95
93
–
Biological Activity
95
92
–
Some of the synthesized compounds were screened in vitro
against some bacteria such as Escherichia coli, Staphylo-
coccus aureus and some fungi such as Aspergillus flavus
and Candida albicans. Gentamycin was taken as a positive
reference for antibacterial activity. The results are tabu-
lated in (Table 1), which shows that the samples have high
antibacterial and moderate antifungal activities on the
tested microorganisms. The results revealed that com-
pounds 3, 8, 21c were found to have an excellent anti-
bacterial activity against E. coli and S. aureus, while
compounds 6, 15b, 19c, 20b exhibited a moderate anti-
bacterial activity and compounds 4, 5 showed only a slight
antibacterial activity. Furthermore, compounds 3 and 8
were found to be excellent antifungals. Moreover, the
biological activities of some tested compounds after
propoxylation showed a greater variation than those with-
out propylene oxide.
93
91
93
90
89
–
93
91
The error of calculations was: biodegradation rate = 0.5 %
increasing numbers of propylene oxide units [31], while the
foam height is found to increase [32]. The surface active
properties were independent of the heterocyclic moiety but
dependent on the hydrophobic (C18) and hydrophilic
(propylene oxide) units; however, the heterocyclic moiety
reveals biological activities of the synthesized molecules,
i.e. these compounds are used as effective emulsifying
agents in many fields, such as cosmetics, formulations,
pesticides, dyes, textiles, etc.
Surface Active Properties
Nonionic surfactants are used in diverse applications, both
in industry and at home. Their moderate foaming and good
detergency are employed in a variety of ways in the leather
industry [27]. It is used to accelerate soaking, and liming is
improved by the addition of wetting agents [28]. In addi-
tion, nonionic surfactants are used extensively because of
their good detergency, easy rinsing and low foaming in the
cleaning of milk and beer bottles. The surface active and
related properties of the synthesized compounds including,
surface and interfacial tension, cloud point, wetting time,
foaming, and emulsification properties are given in
(Table 2).
Biodegradability
For keeping the environment free from pollution, the bio-
degradability of the synthesized compounds was evaluated,
which was determined by the die-away test, followed by
surface tension measurements [33]. The biodegradability
data are given (Table 3) within the experimental accuracy;
all the prepared nonionic surfactants seem to degrade
easily. Biodegradation of these compounds was found to
depend mainly on the propylene oxide chain length when
they had the same hydrophobic part. Also, the results
showed that on the first day 40–50 % of the surfactants was
biodegradable, and after that they disappeared completely
after 6 days, which means that these compounds are
safe for human beings as well as for the environment
(Table 4).
The data in Table 2 show that the surface and interfacial
tensions increased upon increasing the number of propyl-
ene oxide units added to the molecule [29]. All these
compounds show high cloud points, when in hot water,
which increased with an increasing number of moles
of propylene oxide [30]. Also, the synthesized com-
pounds exhibited efficient wetting properties that wetting
time decreased with increasing numbers of propylene
oxide units. Emulsion stability is found to decrease with
123

J Surfact Deterg
Table 4 The number of chemicals
123

J Surfact Deterg
related nitrogen heterocyclic ring systems. Grasas Aceites 59:
110–420
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¨
JO, Ru¨schgen KM, Schafer HJ, Schneider MP (2000) New syn-
R. El-Sayed graduated from the Faculty of Science, Benha University,
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main object of his work is the development of novel approaches for the
synthesis of heterocyclic compounds. He currently works as an
assistant professor in the Chemistry Department, College of Applied
Sciences, Umm Al-Qura University, Makkah, Saudi Arabia.
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123