Synthesis, anticorrosion, antibacterial, and antifungal activity of new amphiphilic compounds possessing quinazolin-4(3H)-one scaffold

Article abstract of DOI:10.1007/s11172-020-3023-0

For the first time, quinazolin-4(3H)-one-based cationic surfactants were prepared and fully characterized by IR and NMR spectroscopic techniques and elemental analysis. Some of their physicochemical properties, such as density, critical micelle concentrat

Full text of DOI:10.1007/s11172-020-3023-0

Russian Chemical Bulletin, International Edition, Vol. 69, No. 11, pp. 2205—2214, November, 2020
2205
Synthesis, anticorrosion, antibacterial, and antifungal activity
of new amphiphilic compounds possessing quinazolin-4(3H)-one scaffold
S. Öztürk,a S. Okay,b,c and A. Yıldırıma
aDepartment of Chemistry, Bursa Uludağ University,
Bursa 16059, Turkey.
E-mail: serkanozturk@uludag.edu.tr
bDepartment of Biology, Çankırı Karatekin University,
Çankırı 18100, Turkey
cVaccine Institute, Hacettepe University,
Ankara 06230, Turkey
For the first time, quinazolin-4(3H)-one-based cationic surfactants were prepared and
fully characterized by IR and NMR spectroscopic techniques and elemental analysis. Some of
their physicochemical properties, such as density, critical micelle concentration, surface tension,
effectiveness in surface tension reduction, Gibbs free energy of micellization, foam and emul-
sion stability, and anticorrosion activity were determined. Antibacterial and antifungal activities
of the synthesized compounds were investigated. N,N-Dimethyl-N-{2-[(2-methyl-4-oxo-
quinazolin-3(4H)-yl)amino]-2-oxoethyl}tetradecan-1-aminium chloride (4a) showed the
highest antibacterial activity against five human pathogens. Antifungal activity against Candida
albicans was shown only by surfactant 4a.
Key words: anticorrosion activity, antibacterial activity, antifungal activity, heterocyclic
surfactants, quinazolin-4(3H)-one, Gibbs free energy of micellization.
Scheme 1
Nitrogen-containing heterocyclic compounds are an
important class of organic compounds due to their diverse
biological activities. The representatives of this class of
heterocycles are the derivatives of quinazolin-4(3H)-one
(also known as 4-oxo-quinazoline).1 The name quinazo-
line, earlier known as benzo-1,3-diazine, was first proposed
for this bicyclic compound by Weddige.2 The facile syn-
thesis of quinazolin-4(3H)-one by heating the starting
material anthranilic acid with excess formamide in an open
vessel at 120 C is known as Niementowski reaction3
(Scheme 1). Another procedure employed by Jiang and
co-workers4 involved the treatment of 5-chloroanthranilic
acid with acetic anhydride to afford the benzoxazinone in
76% yield. Subsequent stirring of benzoxazinone with
ammonium acetate at an elevated temperature afforded
6-chloro-2-methylquinazolin-4(3H)-one in 54% yield
(Scheme 2). Similar reaction was also performed in good
yields by Nouira et al.5 under microwave irradiation con-
ditions (200 W) over 10 min at 200 C. These findings
clearly indicate that significant advancement has been
made in recent years in the synthesis of these heterocyclic
compounds.
Scheme 2
i. Ac2O, reflux; ii. NH4OAc, 150 C, 0.5 h.
Heterocyclic compounds with quinazolin-4(3H)-one
skeleton garnered great interest because of their biological
activities, such as anticancer,6—8 antimicrobial,9—11 an-
tifungal,12 anti-inflammatory,11,13—15 analgesic,13—16
anticonvulsant,16,17 antitumor,18,19 antiviral,20,21 and
antibacterial13,14,22,23 properties.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2205—2214, November, 2020.
1066-5285/20/6911-2205 © 2020 Springer Science+Business Media LLC

Öztürk et al.
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Russ. Chem. Bull., Int. Ed., Vol. 69, No. 11, November, 2020
(s, 6 H, N+(CH3)2); 2.56 (s, 3 H, CCH3); 1.78 (quint, 2 H,
CH2CH2N+(CH3)2, J = 7.0 Hz); 1.59 (quint, 2 H, CH2CH2-
CH2N+(CH3)2, J = 7.0 Hz); 1.24—1.20 (m, 20 H, CH2); 0.83
(t, 3 H, CH2CH3), J = 7.0 Hz). 13C NMR,  165.39 (HNC=O);
160.45 (C=O in quinazolinone); 155.93 (N=C(CH3)N); 147.05
(1 C, Ar); 134.35 (1 C, Ar); 127.06 (1 C, Ar); 126.36 (1 C, Ar);
126.30 (1 C, Ar); 120.18 (1 C, Ar); 65.34 (C(O)CH2N+(CH3)2);
64.23 ((CH3)2N+CH2CH2); 56.89 (CCH3); 50.47 (C(O)CH2N+-
(CH3)2); 31.74—22.34 (11 C, CH2); 21.62 (CH2CH3); 14.38
(CH2CH3).
In recent years, studies have been carried out on the
synthesis of quinazolin-4(3H)-one derivatives containing
long alkyl chain. These quinazolinone derivatives have
found important applications in industrial areas as metal-
lic corrosion inhibitors24,25 and in pharmacology as anti-
microbial agents.26—29 In long chain quinazolinone de-
rivatives having antimicrobial activity, the long carbon
chain is bound to the quinazoline carbon atom located
between two nitrogen atoms.
N,N-Dimethyl-N-{2-oxo-2-[(4-oxo-2-phenylquinazolin-3(4H)-
yl)amino]ethyl}tetradecan-1-aminium chloride (4b). Yellow waxy
solid. Yield 98%. Found (%): C, 69.29; H, 8.48; N, 9.99.
C32H47ClN4O2. Calculated (%): C, 69.23; H, 8.53; N, 10.09.
IR, /cm–1: 3210 (N—H, amide), 3100 (CAr—H); 1686 (C=O,
cyclic amide); 1591 (C=O, amide). 1H NMR, : 8.12 (d, 1 H,
Ar, J = 7.8 Hz); 7.91 (t, 2 H, Ar, J = 7.7 Hz); 7.76 (d, 2 H,
Ho in Ph, J = 7.8 Hz); 7.69 (d, 1 H, Ar, J = 7.8 Hz); 7.62 (t, 1 H,
Ar, J = 7.7 Hz); 7.54 (t, 2 H, Hm in Ph, J = 7.7 Hz); 7.47 (t, 1 H,
Hp in Ph, J = 7.7 Hz); 5.65 (s, 1 H, HNC=O); 3.25 (s, 2 H,
C(O)CH2N+); 2.93 (t, 2 H, CH2CH2N+, J = 7.7 Hz); 2.48
(s, 6 H, CH3N+CH3); 1.75 (quint, 2 H, CH2CH2N+(CH3)2,
J = 7.0 Hz); 1.51 (quint, 2 H, CH2CH2CH2N+(CH3)2,
J = 7.0 Hz); 1.26—1.17 (m, 20 H, CH2), 0.83 (t, 3 H, CH2CH3,
J = 7.0 Hz). 13C NMR, : 164.91 (HNC=O); 159.33 (C=O in
quinazolinone); 155.90 (N=C(Ph)N); 146.95 (1 C, Ar); 139.69
(1 C, Ar); 129.31 (1 C, Cp in Ph); 128.99 (2 C, Cm in Ph); 128.42
(1 C, Cipso in Ph); 128.19 (2 C, Co in Ph); 128.01 (1 C, Ar);
127.41 (1 C, Ar); 126.99 (1 C, Ar); 121.10 (1 C, Ar); 65.05 (C(O)-
CH2N+(CH3)2); 60.99 ((CH3)2N+CH2CH2); 51.74 (C(O)-
CH2N+(CH3)2); 31.73—26.08 (11 C, CH2); 22.53 (CH2CH3);
14.39 (CH2CH3).
N,N-Dimethyl-N-{2-[(2-methyl-4-oxoquinazolin-3(4H)-yl)-
amino]-2-oxoethyl}hexadecan-1-aminium chloride (5a). Yellow
waxy solid. Yield 96%. Found (%): C, 66.79; H, 9.51; N, 10.69.
C29H49ClN4O2. Calculated (%): C, 66.83; H, 9.48; N, 10.75.
IR, max/cm–1: 3245 (N—H, amide); 1672 (C=O, cyclic amide);
1608 (C=O, amide). 1H NMR, : 8.08 (d, 1 H, Ar, J = 8.0 Hz);
7.84 (t, 1 H, Ar, J = 7.7 Hz); 7.75 (t, 1 H, Ar, J = 7.7 Hz); 7.58
(d, 1 H, Ar, J = 7.8 Hz); 5.80 (s, 1 H, HNC=O); 3.09 (s, 2 H,
C(O)CH2N+); 2.92 (t, 2 H, CH2CH2N+, J = 7.7 Hz); 2.66
(s, 6 H, N+(CH3)2); 2.57 (s, 3 H, CCH3); 1.78 (quint, 2 H,
CH2CH2N+(CH3)2, J = 7.0 Hz); 1.60 (quint, 2 H, CH2-
CH2CH2N+(CH3)2, J = 7.0 Hz); 1.26—1.18 (m, 24 H, CH2);
0.83 (t, 3 H, CH2CH3, J = 7.0 Hz). 13C NMR, : 165.50
(HNC=O); 160.45 (C=O in quinazolinone); 155.92 (N=C-
(CH3)N); 147.05 (1 C, Ar); 134.34 (1 C, Ar); 127.06 (1 C, Ar);
126.35 (1 C, Ar); 126.30 (1 C, Ar); 120.18 (1 C, Ar); 65.35 (C(O)-
CH2N+(CH3)2); 64.19 ((CH3)2N+CH2CH2); 56.87 (CCH3);
50.49 (C(O)CH2N+(CH3)2); 31.74—24.09 (13 C, CH2), 22.53
(CH2CH3); 14.38 (CH2CH3).
In the present study, quinazolin-4-one-derived cat-
ionic surfactants were synthesized and characterized using
Fourier transform infrared (FT-IR) and NMR spectro-
scopy. Antibacterial and antifungal activities of the syn-
thesized compounds were investigated.
Experimental
Reagents and solvents were purchased from Merck (Germany).
A Thermo Nicolet 6700 FT-IR spectrometer (USA) was used
for acquisition of the attenuated total reflectance FT-IR spectra.
The NMR spectra were measured on an A600a Agilent DD2
600 MHz NMR spectrometer (USA) in DMSO-d6 at working
frequencies of 600 (1H) and 150 MHz (13C). The elemental
analyzes were performed with a LECO CHNS-932 elemental
analyzer (USA).
2-Methyl-4H-benzo[d][3,1]oxazin-4-one (1a) used as the
starting material in the synthesis was purchased from Merck.
2-Phenyl-4H-benzo[d][3,1]oxazin-4-one (1b) was synthesized
from anthranilic acid as previously described.20 Synthesis of
3-amino-2-methylquinazolin-4(3H)-one (2a) and 3-amino-2-
phenylquinazolin-4(3H)-one (2b) were carried out according to
the earlier developed method.14,20
Synthesis of compounds 3a,b. A solution of 1 equiv. of amine
2a or 2b and 1.5 equiv. of chloroacetyl chloride in DMF was
refluxed for 6 h. After completion of the reaction, the reaction
mixture was cooled, treated with ice-cold water, the precipitate
obtained was collected by filtration, washed with water, dried,
and crystallized from ethanol to give 2-chloro-N-(2-methyl-4-
oxoquinazolin-3(4H)-yl)acetamide (3a) and 2-chloro-N-(4-oxo-
2-phenylquinazolin-3(4H)-yl)acetamide (3b). Physicochemical
and spectral properties of compounds 3a and 3b are in agreement
with those published earlier.30
Synthesis of surfactants 4a,b, and 5a,b (general procedure).
A mixture of 1 equiv. of compound 3a or 3b, 1 equiv. of long-
chain tertiary amine and EtOH were heated at 120 C for 48 h.
After completion of the reaction, the mixture was cooled and the
excess of solvent was removed under reduced pressure. The
residue was washed three times with diethyl ether—petroleum
ether (1 : 3).31 A yellow waxy products were obtained quantita-
tively in sufficient purity.
N,N-Dimethyl-N-{2-oxo-2-[(4-oxo-2-phenylquinazolin-
3(4H)-yl)amino]ethyl}hexadecan-1-aminium chloride (5b). Yellow
waxy solid. Yield 98%. Found (%): C, 70.10; H, 8.74; N, 9.55.
C34H51ClN4O2. Calculated (%): C, 70.02; H, 8.81; N, 9.61. IR,
max/cm–1: 3225 (N—H, amide); 3110 (CAr—H); 1687 (C=O,
cyclic amide); 1591 (C=O, amide). 1H NMR, : 8.16 (d, 1 H,
Ar, J =7.8 Hz); 7.91 (d, 2 H, Ho in Ph, J = 7.8 Hz); 7.73 (t, 1 H,
Ar, J = 7.7 Hz); 7.60 (d, 2 H, Ar, J = 7.8 Hz); 7.53 (t, 2 H,
N,N-Dimethyl-N-{2-[(2-methyl-4-oxoquinazolin-3(4H)-yl)
amino]-2-oxoethyl}tetradecan-1-aminium chloride (4a). Yellow
waxy solid. Yield 93%. Found (%): C, 65.69; H, 9.24; N, 11.31.
C
27H45ClN4O2. Calculated (%): C, 65.76; H, 9.20; N, 11.36.
IR, /cm–1: 3250 (N—H, amide); 1672 (C=O, cyclic amide);
1608 (C=O, amide). 1H NMR, : 8.08 (d, 1 H, Ar, J = 8.0 Hz);
7.84 (t, 1 H, Ar, J = 7.7 Hz); 7.76 (t, 1 H, Ar, J = 7.7 Hz); 7.58
(d, 1 H, Ar, J = 7.8 Hz); 5.80 (s, 1 H, HNC=O); 3.08 (s, 2 H,
C(O)CH2N+); 2.92 (t, 2 H, CH2CH2N+, J = 7.7 Hz); 2.66
H
m in Ph, J = 7.7 Hz); 7.45 (t, 1 H, Hp in Ph, J = 7.7 Hz); 5.69
(s, 1 H, HNC=O); 3.28 (s, 2 H, O=CCH2N+); 2.91 (t, 2 H,

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Russ. Chem. Bull., Int. Ed., Vol. 69, No. 11, November, 2020
2207
CH2CH2N+, J = 7.7 Hz); 2.48 (s, 6 H, N+(CH3)2); 1.77 (quint,
2 H, CH2CH2N+(CH3)2, J = 7.0 Hz); 1.51 (quint, 2 H,
CH2CH2CH2N+(CH3)2, J = 7.0 Hz); 1.25—1.15 (m, 24 H, CH2);
0.81 (t, 3 H, CH2CH3, J = 7.0 Hz). 13C NMR, : 164.83
(HNC=O); 159.28 (C=O in quinazolinone); 155.92 (N=C(Ph)N);
146.98 (1 C, Ar); 139.85 (1 C, Ar); 129.26 (1 C, Cp in Ph); 129.07
(2 C, Cm in Ph); 128.93 (1 C, Cipso in Ph); 128.33 (2 C, Co in
Ph); 128.13 (1 C, Ar); 127.40 (1 C, Ar); 126.95 (1 C, Ar); 121.13
(1 C, Ar); 65.07 (C(O)CH2N+(CH3)2); 61.09 ((CH3)2N+-
CH2CH2); 51.95 (C(O)CH2N+(CH3)2); 31.75—26.18 (13 C,
CH2); 22.55 (CH2CH2); 14.35 (CH2CH3).
Critical micelle concentration (CMC) the surfactants was
determined using the conductometric method. Conductivity
measurements were performed using a Thermo Scientific ORION
3 STAR digital conductometer (USA). The specific conductiv-
ity of the surfactant was measured by the step-by-step dilution-
extraction method. The CMC values were estimated from the
break point on the curve of electric conductivity versus surfactant
concentration.
HCl before the immersion test. Then the coupons were slightly
polished with paper tissue, washed with deionized water, and
dipped in acetone. The corrosion tests of compounds 4a,b and
5a,b were performed in 1.0 M HCl solution prepared from the
concentrated HCl (37%, Merck). The solutions of cationic sur-
factants with the concentration of 10, 25, 50, 100, and 250 ppm
prepared by dissolving the test surfactant in the acid solution,
were poured into 150-mL sealed glass bottles. The coupons were
immersed in these solutions without stirring for 24 h at room
temperature. After the test time, the coupons were removed,
rinsed with water, wiped with paper tissues, washed with acetone,
and dried to a constant weight in an oven at 40 C. Control tests
were performed in the same way without the inhibitors.
Antibacterial activity was tested on the human pathogens
extended-spectrum -lactamase (ESBL)-producing Escherichia
coli (ATCC 35218), methicillin-resistant Staphylococcus aureus
(clinical isolate), Klebsiella pneumoniae (ATCC 700603), Pseudo-
monas aeruginosa (ATCC 27853), and Enterococcus faecalis
(ATCC 291212). For the disk-diffusion assay, bacteria were grown
in nutrient broth (NB; LabM Limited, UK) at 37 C for 24 h
diluted in sterile saline (0.85% NaCl) solution to McFarland 0.5,
and spread on nutrient agar (NA; LabM Limited, UK) plates.
The surfactants (2 μg) dissolved in DMSO were added on blank
disks (Oxoid, UK) placed on bacteria. Erythromycin (15 μg) and
chloramphenicol (30 μg) disks (Oxoid, UK) were used as standard
antibiotics, and DMSO was used as a negative control. The plates
were incubated overnight at 37 C, and the diameters of zones
without bacterial growth around the disks were measured. All
samples were assayed in triplicates.
The minimum inhibitory concentration (MIC) assay was
performed using the same human pathogens grown in NB and
diluted to McFarland 0.5. Suspensions of bacteria (200 μL) of
were added to the wells of a 96-well plate, and serial two-fold
dilution of the surfactants from 20 to 0.625 g mL–1 concentra-
tion was performed. The plates were covered and incubated at
37 C for 24 h. The optical density (OD) of the bacterial growth
was measured at 630 nm using RT-2100C microplate reader
(Rayto, China). All samples were assayed in duplicates. The
lowest concentration providing an 80% growth reduction as
compared to negative control (DMSO) was accepted as MIC.38
Antifungal activity was tested on Candida albicans (ATCC
10231). The culture of C. albicans was prepared in potato dextrose
broth (PDB; Merck, Germany) at 37 C for 24 h. The culture
was diluted to McFarland 0.5 using sterile saline solution, and
spread on potato dextrose agar (PDA; Merck, Germany) plates.
The surfactants (2 μg) of dissolved in DMSO were added on
blank disks placed on C. albicans cells. The plates were incu-
bated overnight at 37 C, and the diameters of growth inhibition
zones around the disks were measured. Fluconazole (25 μg) was
used as a standard. All samples were assayed in triplicates.
Surface tension at the CMC. Surface tensions of the aqueous
solutions of the synthesized cationic surfactants was measured
by the capillary rise method.32,33 A capillary used for the mea-
surement is Na-heparinized micro hematocrit tube (NRIS, Soda
Lime glass, d = 1.0 mm, l = 75 mm). The related values were
measured at 20 C.
Foam properties. The following two parameters of the foam
properties were examined: the foam height and the foam stabil-
ity. The foam height was measured as previously described.34
Twenty-five mL of an aqueous solution of the surfactant at the
CMC was shaken vigorously for 10 s in a calibrated 100-mL glass
cylinder with a glass stopper. The length and diameter of the
cylinder used in the foam height measurements at 20 C were
18 and 2.2 cm, respectively. The solution was allowed to stand
for 30 s and then the foam height was measured. The foam stabil-
ity was determined by measurement of changes in the foam
volume after shaking the aqueous surfactant solutions (10 mL)
at the CMC for 30 s in the same glass cylinder used for foam
height measurements. Foam experiments were carried out at
20 C using ultrapure water (resistivity of 18.2 Mcm) which
was prepared using an Elga Purelab Option Q water purification
system. The measurement of foam volume of the surfactant solu-
tions was performed as described below. The glass cylinder was
sealed and vigorously shaken for 30 s and the initial measurement
was made immediately. The subsequent measurements of the
foam volumes were done 5 and 30 min after shaking.35 The
measurements were repeated twice for each surfactant.
Emulsion stability was determined by mixing the aqueous
solution of the surfactants with the mineral oil in a 100-mL
graduated cylinder with a plastic stopper. A 10 mL of aqueous
surfactant solution at the CMC was poured into a 100-mL cyl-
inder containing 10 mL of the mineral oil. The glass cylinder was
closed with stopper. The mixture was shaken by turning vigor-
ously the glass cylinder up and down for 30 s at constant speed
and then the time for the separation of 9 mL of clean surfactant
solution was noted.36
Results and Discussion
Synthesis of cationic surfactants was performed in three
steps (Scheme 3). In the first two steps, known N-amino-
substituted methyl- and phenylquinazolinones 2a,b and
the corresponding chloroacetamide derivatives 3a,b were
synthesized. In the third step, compounds 3a,b were re-
acted with tertiary amine containing 14 carbon atoms in
the long chain to give compounds 4a,b. The reaction of
Anticorrosion activity test in 1.0 M HCl solution. The corro-
sion test in acidic medium was performed using the coupons
made of cold-rolled low-carbon steel according to DIN EN
1013037 that contains 0.07% C, 0.35% Mn, 0.015% P, and 0.015% S.
Metal coupons cut into rectangular shapes of 0.12.25.0 cm in
thickness, width, and length, respectively, were immersed in 15%

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Russ. Chem. Bull., Int. Ed., Vol. 69, No. 11, November, 2020
Scheme 3
R = Me (a), Ph (b)
compounds 3a,b with the tertiary amine compound con-
taining 16 carbon atoms in the alkyl chain under similar
conditions gave compounds 5a,b. Newly synthesized
cationic surfactants (4a,b and 5a,b) were characterized
using FT-IR and 1H and 13C NMR spectroscopy. FT-IR
and 1H and 13C NMR spectra of compound 4a are shown
in Fig. 1 as an example.
Physicochemical properties of surfactants. Various
physicochemical parameters like density (), critical mi-
celle concentration, surface tension at the CMC (CMC),
surface effectiveness (CMC) and Gibbs free energy of
micellization (Gmic) were measured and/or calculated
for cationic surfactants (Table 1).
The CMC of the cationic surfactants were determined
by conductivity measurements. The CMC values were
determined from the break points in the plots of specific
conductivity versus surfactant concentration39 (Fig. 2). As
seen in Fig. 2, upon an increase in concentration conduc-
tivity also showed a linear increase and the concentration
at which the slope was changed were taken as CMC for
Table 1. Physicochemical properties of the cationic surfactants 4a,b and 5b
Compounda
ρb,c/g mL–1
CMCb•10–5/mol L–1
CMCb/dyn cm–1
CMC/dyn cm–1
Gmic/kJ mol–1
4a
4b
5b
1.0280
1.0283
1.1212
24.04
6.56
9.29
32.74
30.23
32.96
40.06
42.57
39.84
–20.30
–23.46
–22.62
a No measurements for compound 5a were performed.
b At 20 C.
c At CMC of the surfactant.

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Russ. Chem. Bull., Int. Ed., Vol. 69, No. 11, November, 2020
2209
/S cm–1
40
a
a
35
30
25
20
15
3500 3000 2500 2000 1500 1000 /cm–1
10
5
CMC = 24.04
b
5
10
15
20
25
C•105/mol L–1
/S cm–1
b
20
18
16
14
12
10
8
10
5
0

c
6
4
CMC = 6.56
8
10 C•105/mol L–1
2
2
4
6
/S cm–1
45
c
150
100
50
0

Fig. 1. The FT-IR (a), 1H (b) and 13C NMR (c) spectra of com-
pound 4a.
40
35
30
25
20
15
10
5
the synthesized surfactants. The CMC were found to
be equal 24.04•10–5 mol L–1 for compound 4a, and
6.56•10–5 mol L–1 for compound 4b, 9.29•10–5 mol L–1
for compound 5b. From these results, it can be concluded
that the micelles of these cationic surfactants are formed
at low concentrations. Comparing compounds 4a and 4b,
it was found that the CMC of compound 4b was lower
than that of compound 4a. It is notable that surfactants
4a and 4b contain the same carbon chains. The only dif-
ference between compounds 4a and 4b is that compound
4a has a methyl group in the quinazolinone ring and com-
pound 4b has a phenyl ring. The phenyl-substituted com-
pound 4b is more hydrophobic than the methyl-substituted
compound 4a. Note that an increase in the hydrophobic
character of the cationic surfactant leads to a decrease in
the critical micelle concentration. The phenyl group acts
as a hydrophobic unit since it is commonly admitted that
its contribution to the CMC is roughly equivalent to
CMC = 9.29
15
5
10
C•105/mol L–1
Fig. 2. Conductivity as a function of surfactant concentration for
the determination of critical micelle concentration of compounds
4a (a), 4b (b), and 5b (c).
3.5 methylene groups.40 In addition, the CMC value of
compound 5b was slightly higher than that of compound
4b, although the critical micelle concentrations were close
to each other. Compound 5b has a longer carbon chain
and should have a lower CMC value than compound 4b.

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We can explain this result as follows: the hydrophobic
chains in the surfactant molecule has little effect on CMC
when it reaches a certain length. This is because of the
tangling of the excessively long hydrophobic chains hin-
dered effective micellization and the long hydrophobic
chains also weaken the water solubility of surfactant. This
diminished the effect of the chain elongation.41
At the same time, the CMC of the surfactants reflects
the changes in the Gibbs free energy of micellization
(ΔGmic). As the critical micelle concentration of the sur-
factant decreases, the tendency of the substance to form
micelles increases. The ΔGmic value, which is calculated
by Eq. (1), proves this information.
the CMC and reflects the reduction in surface pressure
attained at the CMC. 31 The CMC value can be calculated
from the equation
CMC = 0 – CMC
,
(2)
where 0 is the surface tension of the solvent (for water at
20 C, 0 = 72.8 dyn cm–1), CMC is the surface tension
of solution at the CMC.
The calculated πCMC values or compounds 4a, 4b, and
5b were 40.06, 42.57, and 39.84 dyn cm–1, respectively.
These results indicate that the synthesized cationic
surfactants have the potential to reduce the surface ten-
sion in the aqueous system. It is known that the activity
of the surfactant increases with the increasing the CMC
values. Therefore, compound 4b with the highest CMC
value will show better surface activity than the other
surfactants.
The foam properties of the synthesized cationic sur-
factants were investigated as foam height, foamability
and foam stability (Table 2). These parameters of the
surfactants were studied in water at two concentrations,
namely, at the CMC and concentration higher than CMC
(1•10–3 mol L–1). The initial foam volume (V0, mL) was
reported as the foamability. The initial foam height strongly
depends on the concentration of the surfactants. At higher
concentration the greater foam volumes were obtained.35
When we compared the foam heights and foaming abilities
of the synthesized compounds, it appeared that the form-
ation of foam by compounds 4b and 5b with the phenyl
group at the quinazolinone ring is reduced. This can be
explained in terms of the micellar stability. In conventional
surfactants the very stable micelles cause poor foaming
ability, because rupture of micelles is too slow to generate
foam bubbles.43 Consequently, the foaming ability will be
ΔGmic (J mol–1) = RT ln(CMC),
(1)
where R — is the ideal gas constant, T is temperature (K).
The Gmic become more negative by increasing hydro-
phobic character of the surfactant.42 As shown in Table 1,
compound 4b having the lowest CMC value is more prone
to form the micelles than compound 4a, since its hydro-
phobic character is higher.
Surface tensions (CMC) of the synthesized surfactants
at the CMC were determined according to the capillary
rise method.32,33 The surface tensions were measured to
evaluate the surface activity of the aqueous solution of
cationic surfactant at the CMC. Among the synthesized
cationic surface-active compounds, the lowest surface
tension at the CMC was found for compound 4b. This
indicates that compound 4b exhibits better surface activ-
ity properties than the others.
The effectiveness in surface tension reduction (CMC
)
is also an important parameter to evaluate the surface
activity of the aqueous solution of surfactant at the CMC.
This parameter is closely related to the surface tension at
Table 2. Foam height (h), foam volume (V), and foam stability of the cationic surfactants 4a,b and 5a,b
Surfactant
h/mma
1.0•10–3 mol L–1 CMC
V/mLa
Foam stability (%)
1.0•10–3 mol L–1
CMC
after after after
5 mind 30 mine 5 minf 30 ming
initial
after 5 min
after 30 min
b
c
b
c
b
c
V0
V0
V1
V1
V2
V2
after
4a
4b
5a
5b
148
63
120
58
40
15
52
20
60
20
9
2
—
—
45
15
32
15
7
35
14
28
13
6
1
—
—
86.5
75.0
53.3
75.0
67.3
70.0
46.7
65.0
77.8
75.0
66.7
50.0
1.5
h
h
h
h
h
h
h
h
—
—
—
—
—
—
h
h
h
h
—
—
a At 20 C.
b Foam volume measured at the surfactant concentration of 1•10–3 mol L–1
.
c Foam volume measured at CMC.
d [V1b/V0b]•100%.
e [V2b/V0b]•100%.
f [V1c/V0c]•100%.
g [V2c/V0c]•100%.
h No foam formation.

Novel amphiphilic compounds
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 11, November, 2020
2211
Table 4. Corrosion inhibition efficiencies (IE (%)) cal-
culated for different concentrations of surfactants 4a,b
and 5a,b in 1.0 M HCl for 24 h at room temperature
poor due to the micellar stability. Thus, it can be concluded
that the micelle stability for the surface-active agents 4b
and 5b with the phenyl group at the quinazolinone ring is
higher than that of compounds 4a and 5a with the methyl
group at the heterocycle. The CMC and Gmic values
measured for the surfactants supported this result. In ad-
dition, due to very low h and V0 values, the surfactants 4b
and 5b are promising for oilfield wastewater treatment.44
Moreover, as seen in Table 2, there were no significant
changes between the foam stability measured 5 and 30 min
after foam formation. This means that the synthesized
surfactants form permanent foam.
Surfac- EI (%) at concentration of surfactant/ppm
tant
10
25
50
100
250
4a
4b
5a
5b
95.45
94.95
96.24
90.40
96.44
95.84
96.34
93.86
96.24
96.04
95.84
95.34
96.63
96.83
95.94
95.05
96.34
96.73
96.04
95.74
The emulsion stabilities of the synthesized cationic
surfactants were determined as the time required for the
breakdown of the emulsion formed between surfactant
solution and mineral oil. The emulsion stability of the
synthesized surfactants was also studied at two concentra-
tions (at the CMC and 1.0•10–3 mol L–1) (Table 3). As
seen from Table 3, emulsion stability directly depends on
the concentration. The emulsion stability of the surfactants
at the concentration of 1.0•10–3 mol L–1 was significantly
higher than that at the CMC. In addition, emulsion stabil-
ity was lower for the surfactants with the phenyl group at
the quinazolinone ring. As was mentioned above, the
phenyl-substituted compounds 4b and 5b are more hydro-
phobic than the methyl-substituted compounds 4a and 5a.
Higher hydrophobic character leads to lower water solu-
bility of the surfactant.41 In this way, the emulsion ability
is reduced. However, a comparison of the stability of
emulsion formed by compounds 4a to 5a and 4b to 5b
showed that compounds 5a and 5b with the longer al-
kyl groups produced more stable emulsions than com-
pounds 4a and 4b with shorter alkyl group. The reason for
this situation is the longer hydrophobic chain produces more
viscous solutions. The viscous solutions mitigate the
chances of diffusion. This is leading to increment in emul-
sion stability.45
inhibition capabilities of the synthesized compounds at
different concentrations are given as percentage inhibition
efficiencies (IE), which were calculated using equation
IE = [(W0 – W)/W0]•100 (%),
(3)
where W0 is the weight loss of the coupon in the
absence of an inhibitor, W is the weight loss of the cou-
pon in the same environment in the presence of an
inhibitor.
As seen in Table 4, the synthesized surfactants exhib-
ited excellent corrosion inhibition efficiency in 1.0 M HCl
solution over 24 h at room temperature. At selected concent-
rations, all surfactants exhibited similar inhibitory proper-
ties and it was observed that the inhibition efficiency in-
creased slightly with increasing the inhibitor concentration.
In the general structure of the synthesized cationic
surfactants, there is a long carbon chain that will keep the
water molecules away from the metal surface, the hetero-
atoms (N and O) that will provide adsorption to the metal
surface, and the quinazoline ring. In addition, a positively
charged nitrogen atom will provide solubility in acidic
aqueous medium. The possible inhibition mechanism for
the compounds is shown in Fig. 3. As seen in Fig. 3,
N and O heteroatoms are chemically adsorbed to the metal
surface and the positively charged nitrogen atom is ad-
sorbed by electrostatic interaction.
Antimicrobial activity. Quinazoline and quinazolinone
compounds attract attention in medicinal chemistry due
to their wide range of biological activities such as antibac-
terial, antifungal, antiviral, and antimalarial properties.46
In our study, the antibacterial activity of the synthesized
quinazoline derivatives 4a,b and 5a,b was evaluated via
disk-diffusion assay. According to the diameters of growth
inhibition zones, compound 4a showed the highest anti-
bacterial activity against all tested human pathogens (Table 5).
Compound 4a was found to be more effective against E. coli
and E. faecalis than erythromycin and chloramphenicol.
Compounds 4a,b and 5a,b were also tested for their
antifungal activity against C. albicans using disk-diffu-
sion assay, and only compound 4a showed 12-mm inhi-
bition zone, while fluconazole provided 26-mm inhibi-
tion zone.
Corrosion inhibition tests. Corrosion-inhibiting effi-
ciencies of the synthesized cationic surfactants were ex-
plored in the acidic medium (1.0 M HCl) using weight
loss measurements. Results of the corrosion inhibition
efficiency for the synthesized cationic surfactants at dif-
ferent concentrations are given in Table 4. Corrosion
Table 3. Emulsion stabilities of the cat-
ionic surfactants 4a,b and 5a,b at 20 C
Surfactant
Emulsion stability/s
1.0•10–3 mol L–1 CMC
4a
4b
5a
5b
1636
1185
1792
1468
382
23
—
42

Öztürk et al.
2212
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 11, November, 2020
The minimum inhibitory concentration (MIC) assay
gave results only for 2-methyl-substituted compounds 4a
and 5a (Table 6) because 2-phenyl-substituted compounds
4b and 5b produced self-turbidity therefore the optical
density of the bacteria could not be determined. The MIC
values of compound 4a against all tested human pathogens
were found to be lower than those of compound 5a.
Compound 4a possessed the lowest MIC against ESBL-
producing E. coli and the highest MIC against K. pneu-
moniae. Additionally, this cationic surfactant showed lower
MIC values than chloramphenicol against K. pneumoniae,
E. coli, and E. faecalis as well as the same MIC values
against P. aeruginosa and S. aureus. Compound 5a showed
higher MIC values against K. pneumoniae, P. aeruginosa,
and S. aureus than chloramphenicol, whereas these sub-
stances possessed the same MIC values against E. coli and
E. faecalis.
Chemisorption
Electrostaic
interaction
Our findings showed that surfactants 4a,b containing
14 carbon atoms in the alkyl chain were more effective
than compounds 5a,b with 16 carbon atoms, and the
2-methyl-substituted derivatives 4a, 5a showed higher
activity than 2-phenyl-substituted derivatives 4b, 5b. In
contrast to the reported data that methyl group at position
2 is essential for antimicrobial activity of quinazolinone
compounds46 and substitution in phenyl ring with methoxy
and methyl groups increased the antibacterial activity
of the 3-pyrimidine-1-yl quinazoline derivatives,47 the
Fig. 3. The possible corrosion inhibition mechanism for the
cationic surfactants.
Table 5. Antibacterial activity of compounds 4a,b and 5a,b against human pathogens
Compound
Mean diameter of the growth inhibition zone/mm
K. pneumoniae
E. coli
E. faecalis
P. aeruginosa
S. aureus
4a
4b
5a
5b
10.0 0.6
16.0
0
13.7 0.6
12.7 0.6
9.0 0.6
9.0 0.6
9.0 0.6
11.7 0.6
15.0 0.6
12.7 0.6
9.0 0.6
15.0 0.6
12.3 0.6
c
—
14.7 0.6
9.0 0.6
c
c
—
—
—
c
c
c
c
—
—
—
Chloramphenicol
Erythromycin
DMSOb
8.0 0.6
8.0 0.6
26.7 0.6
25.0 0.6
22.3 0.6
25.0 0.6
10.0 0.6
12.7 0.6
c
c
c
c
c
—
—
—
—
—
a Compounds 4a,b and 5a,b were tested in amount of 2 μg, erythromycin was used in amount
of 15 g and chloramphenicol was used in amount of 30 g.
b DMSO was added in amount of 10 L.
c No inhibition.
Table 6. Minimum inhibitory concentrations (g mL–1) of compounds 4b and 5b against
human pathogens
Compounda
K. pneumoniae E. coli
E. faecalis
P. aeruginosa S. aureus
4a
5a
5
1.25
10
2.5
10
10
2.5
10
2.5
20
20
10
Chloramphenicol
DMSO
10
2.5
2.5
b
b
b
b
b
—
—
—
—
—
a No measurements for compounds 4b and 5b were performed.
b No inhibition.

Novel amphiphilic compounds
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 11, November, 2020
2213
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than 2-methyl quinazolines was found by Abd-Elha-
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workers.49 Moreover, it have been shown that introduc-
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methyl increases the analgesic and anti-inflammatory
activities.14
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the synthesized cationic surfactants were investigated.
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Received October 10, 2019;
in revised form February 11, 2020;
accepted August 14, 2020