Synthesis and Antibacterial Evaluation of Benzofuran Based Di-1,2,3-triazoles

Article abstract of DOI:10.1134/S1070363218070265

A series of novel benzofuran-1,2,3-triazole hybrid molecules are synthesized using the click chemistry approach. Structures of the synthesized compounds were assessed by IR, NMR, and mass spectroscopy. The tests of final products 10a–10l for their antibacterial activity demonstrate excellent to good activity against gram-positive and gram-negative bacteria.

Full text of DOI:10.1134/S1070363218070265

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 7, pp. 1515–1524. © Pleiades Publishing, Ltd., 2018.
Synthesis and Antibacterial Evaluation of Benzofuran
1
Based Di-1,2,3-triazoles
a
b
b
a
c
V. Sunitha *, A. Kishore Kumar , P. Shankaraiah , P. Jalapathi , and Ch. A. Lincoln
a
Department of Chemistry, University College of Science, Osmania University,
Saifabad, Hyderabad, Telangana, 500004 India
*
e-mail: vinalasunitha@gmail.com
b
3
Department of Humanities and Sciences, Vardhaman College of Engineering,
Shamshabad, Hyderabad, Telangana, 501218 India
Department of Chemistry, University College of Science, Osmania University,
Hyderabad, Telangana, 500007 India
Received May 30, 2018
Abstract—A series of novel benzofuran-1,2,3-triazole hybrid molecules are synthesized using the click
chemistry approach. Structures of the synthesized compounds were assessed by IR, NMR, and mass
spectroscopy. The tests of final products 10a–10l for their antibacterial activity demonstrate excellent to good
activity against gram-positive and gram-negative bacteria.
Keywords: benzofuran, 1,2,3-triazoles, click chemistry, antibacterial activity
DOI: 10.1134/S1070363218070265
INTRODUCTION
Encouraged by the biological activities of benzo-
furans and 1,2,3-triazoles we successfully synthesized
novel benzofuran based di-1,2,3-triazole compounds
10a–10l. Another objective of the current study was to
test antibacterial activity of benzofuran-1,2,3-triazole
hybrids 10a–10l with the ultimate aim of developing
novel potent antibacterial agents.
Benzofuran derivatives display potent biological
properties including analgesic [1], antihyperglycemic
2], antimicrobial [3], antiparasitic [4], antitumor, and
kinase inhibitor [5, 6] activities. Substituted benzo-
furans are used as fluorescent sensors [7], oxidants [8],
brightening agents, and some others [9].
[
RESULTS AND DISCUSSION
1
,2,3-Triazoles are important heterocyclic com-
pounds that received considerable attention due to
wide range of their applications in biochemical,
pharmaceutical and material sciences [10-17]. They
make attractive bridging units, since they are stable
under oxidative/reductive and metabolic degradation
conditions, and actively participate in dipole-dipole
interactions and hydrogen bonding [18]. These
moieties can be shaped into powerful pharmacophores
that can play an important role in bio-conjugation.
Copper(I) catalyzed synthesis of 1,4-disubstituted
{
6-[(1-[4-([1H-1,2,3-Triazol-4-yl]methoxy)phenyl]-
H-1,2,3-triazol-4-yl)methoxy]-3-methylbenzofuran-2-
yl}phenylmethanones 10a–10l were synthesized by a
-step protocol (Scheme 1). Formation of substituted
3-methyl-6-(prop-2-yn-1-yloxy)benzofuran-2-yl]-
1
6
[
phenylmethanone 5a–5c was readily achieved by
reacting 1-[2-hydroxy-4-(prop-2-yn-1-yloxy)phenyl]-
ethanone 3 with substituted phenacyl bromides 4a–4c
in base-mediated reaction. Structures of the com-
1
pounds 5a–5c were confirmed by H NMR spectra,
1
,2,3-triazoles [19] from terminal alkynes and azides
that demonstrated singlets at 2.61–2.63 ppm for three
protons suggesting the presence of the methyl group
and a doublet at 4.77–4.78 ppm assigned to two
protons and a triplet at 2.56–2.57 ppm assigned to the
single proton suggesting the presence of the O–CH
and ≡CH groups. In C NMR spectra of compounds
5a–5c, the carbonyl, ≡C, ≡CH, and O–CH carbons
became a common method for rapid synthesis of
organic and bioorganic compounds [20]. Therefore, the
well recognized click route [21] was applied in
generating 1,2,3-triazole derivatives.
2
1
3
1
The text was submitted by the authors in English.
2
1
515

1
516
SUNITHA et al.
Scheme 1. Synthesis of benzofuran based di-1,4-disubstituted 1,2,3-triazoles (10a–10l).
Me
Me
Br
AcOH, ZnCl2
O
O
o
1
3
20−140 C
K CO , acetone
reflux, 8 h, 92%
2
3
HO
OH
HO
OH
O
OH
0 min, 76%
1
2
3
O
Br
R
4
a−4c
R
N
Br
N
N
OH
HO
O
O
DMF, NaH
h,
room temperature
1
O
N3
Me
6
7
a−7c
.
CuSO4 5H O
2
sodium ascorbate
DMF + H O (1 : 1),
R
2
room temperature
R
Me
N
N
N
O
O
O
O
O
O
5
a−5c
O
Me
8a−8c
.
CuSO4 5H O
2
N −R1
sodium ascorbate
3
DMF + H O (1 : 1),
9
a−9d
2
room temperature
N
O
R
1
N
N
R
N
N
N
O
O
O
1
0a−10l
Me
R = H (5a), Br (5b), Cl (5c); R = H, R
1
= C
6
H
13 (10a), R = H, R
1
= C
8
H
17 (10b), R = H, R
= C (10g), R = Br, R
= p-ClC (10l).
1
= C
6
H
5
(10c), R= H, R
1
=
p-ClC (10d), R = Br, R = C 13 (10e), R = Br, R
6
H
4
1
6
H
1
= C 17 (10f), R = Br, R
8
H
1
6
H
1
5
1
= p-ClC (10h),
6 4
H
R = Cl, R = C 13 (10i), R = Cl, R = C 17 (10j), R = Cl, R
1
6
H
1
8
H
1
= C (10k), R = Cl, R
6
H
5
6 4
H
were recorded at 183.0–183.4, 77.9, 76.2, and 56.2, res-
4-Azidophenol 6 was synthesized from 4-amino-
pecttively. In IR spectra of compounds 5a–5c, a band
phenol using the diazotization reaction followed by
–
1
between 1640–1649 cm (C=O) and disappearance of
treatment with NaN . Using click chemistry substituted
3
–
1
the band at 3440–3411 cm (OH) confirmed forma-
{6-[(1-(4-hydroxyphenyl)-1H-1,2,3-triazol-4-yl)meth-
oxy]-3-methylbenzofuran-2-yl}phenylmethanones 7a–
tion of compounds 5a–5c.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 7 2018

SYNTHESIS AND ANTIBACTERIAL EVALUATION OF BENZOFURAN
Antibacterial activity of the compounds 10a–10l
1517
Zone of inhibition, mm
gram positive bacteria
MRSA
gram negative bacteria
Comp. no.
1
0a
0b
75
No activity
05
08
No activity
No activity
09
11
07
09
08
11
24
27
12
15
13
16
18
21
21
24
17
21
15
18
20
23
25
28
31
34
No activity No activity
No activity No activity
07
No activity
1
00
No activity
08
10
No activity
07
1
75
No activity No activity
No activity No activity
07
10
07
10
22
25
10
13
11
14
19
22
20
24
18
21
14
17
19
22
24
28
28
31
06
09
08
11
24
27
09
12
12
15
20
24
20
23
17
22
13
17
20
23
26
29
27
30
No activity
1
00
11
No activity
09
1
0c
75
09
08
12
25
28
11
13
13
16
19
22
23
26
17
20
15
18
20
23
26
29
31
33
No activity
No activity
08
1
00
12
No activity
23
No activity
26
10
1
0d
75
28
24
1
00
31
26
29
28
1
0e
75
10
11
11
09
1
00
13
14
14
12
1
0f
75
13
12
14
12
1
00
16
15
17
14
1
0g
0h
75
20
20
17
20
1
00
23
23
20
24
1
75
26
22
24
23
1
00
30
25
27
26
1
0i
75
18
20
16
20
1
00
21
23
19
23
1
0j
75
14
16
14
12
1
00
17
19
17
15
1
0k
75
22
21
22
20
1
00
25
24
26
23
1
0l
75
29
24
28
27
1
00
Zentamicin 75
00
32
27
31
31
27
30
31
29
1
30
33
33
31
1
7
c were synthesized by the cycloaddition reaction of a
substituted [3-methyl-6-(prop-2-yn-1-yloxy)benzo-furan-
-yl]phenylmethanone 5a–5c with 4-azido-phenol 6
characterized by IR, NMR and Mass spectral data. H
NMR spectra of compounds 7a–7c exhibited
characteristic singlets at 9.97–9.43, 5.34–5.32, and
2.61–2.57 ppm suggesting the presence of phenolic
2
which gave the corresponding 1,2,3-triazole deriva-
tives 7a–7c. Structures of the compounds 7a–7c were
1
3
OH, O–CH , and CH protons, respectively. In
C
2
3
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 7 2018

1
518
SUNITHA et al.
NMR spectra of compounds 7a–7c the signals of car-
pelleted in KBr. NMR spectra were measured for
bonyl, O–CH and CH carbons were recorded at 185.3–
CDCl solutions on a Bruker AV-400 and AV-300
2
3
3
1
83.1, 62.2–61.6 and 10.1–9.9 ppm respectively.
spectrometers using TMS as an internal standard. CHN
analysis was carried out on a Perkin Elmer Model
O-Propargylation of compounds 7a–7c was carried
2
400 CHNS elemental analyzer. Electron Spray
out by propargyl bromide and sodium hydride in dry
DMF under N atmosphere affording O-alkylated com-
pounds 8a–8c. The targeted regioselective benzofuran
based di-1,4-disubstituted 1,2,3-triazole derivatives
Ionization (ESI) mass spectra were recorded on a
QSTARXL hybrid MS system (Applied Bio Systems).
TLC was carried out on Merck TLC silica gel 60 F254
plates. The spots were visualized under UV light at
2
1
0a–10l were synthesized by the cycloaddition
reaction of different substituted {3-methyl-6-[(1-[4-
prop-2-yn-1-yloxy)phenyl]-1H-1,2,3-triazol-4-yl)-
2
54 nm or, alternatively, by staining with aqueous
basic potassium permanganate. Column chromato-
graphy was performed on a Merck silica gel 60A (100–
(
methoxy]benzofuran-2-yl}phenylmethanones 8a–8c
with an aromatic or aliphatic azide 9a–9d.
2
00 mesh).
Synthesis of 1-(2,4-dihydroxyphenyl)ethanone
2). A mixture of acetic acid (3 g, 0.05 mol) with
freshly fused zinc chloride (6.8 g, 0.05 mol) was
heated at 120°C for 30 min, then resorcinol (5.5 g,
.05 mol) was added. The reaction mixture was heated
at 140°C for 30 min. The process was monitored by
TLC. Upon completion of the reaction, the mixture
was cooled to room temperature, poured into ice cold
water (100 mL) and extracted with ethyl acetate (3×
50 mL). The combined organic layers were washed
Structures of the synthesized compounds were
elucidated from IR, NMR and Mass spectral data. In
IR spectra of the compounds 10a–10l the band at 1656–
(
–
1
1
1
639 cm indicated the presence of ketone. H NMR
0
spectra of compounds 10a–10l exhibited four singlets
at 8.14–8.10, 5.39–5.34, 5.28–5.24, and 2.68–2.66 ppm
that indicated the presence of triazole, CH and the
2
methyl group protons, respectively.
The newly synthesized benzofuran based di-1,4-
disubstituted 1,2,3-triazoles 10a–10l were tested for
their antibacterial activity in concentrations of 75 and
with 20% HCl (50 mL), saturated NaHCO (25 mL)
3
and brine (2×25 mL), dried over anhydrous sodium
sulphate, filtered and concentrated under reduced
pressure. The crude product was purified by column
chromatography using 100–200 mesh silica gel, eluted
by 10% ethyl acetate/pet ether to afford 1-(2,4-dihyd-
roxyphenyl)ethanone as reddish-brown needles. Yield
76%, mp 142–144°C [22].
1
00 μg/mL against four Gram positive bacteria (vize
Micrococcus luteus, Methcillin-resistant Staphylococcus
aureus, Bacillus subtilis, Bacillus cereus), and four
Gram negative bacteria (vize Pseudomonas aeruginosa,
Klebsiella pneumoniae, Escherichia coli, and Proteus
vulgaris) using Gentamycin sulphate as a standard
drug. The accumulated data demonstrated high
inhibitory effects of the products on growth of the
tested bacterial strains (see the table).
Synthesis of 1-[2-hydroxy-4-(prop-2-yn-1-yloxy)-
phenyl]ethanone (3). To a well-stirred mixture of
-(2,4-dihydroxyphenyl)ethanone 2 (3 g, 0.019 mol)
1
The compounds 10l, 10d, 10h, 10k, and 10g
demonstrated the highest activity (see the table). It is
noteworthy that the compounds with strong electron
withdrawing atoms like chloro and bromo groups on
phenyl ring attached to triazole may initiate the
antibacterial activity unlike aliphatic and phenyl
substituted triazoles.
dissolved in dry acetone with K CO (2.72 g, 0.019 mol),
2
3
propargyl bromide 80% in toluene (2.34 g, 0.019 mol)
was added dropwise. The reaction mixture was
refluxed for ca 8 h. Progress of the reaction was
monitored by TLC. Upon completion of the process,
the reaction mixture was cooled to room temperature
and acetone was evaporated under reduced pressure.
The mixture was diluted by water (50 mL) and
extracted with ethyl acetate (3×50 mL). The combined
organic layers were washed with brine (2×25 mL),
dried over anhydrous sodium sulphate, filtered, and
concentrated in vacuo. The crude product was purified
by column chromatography using 100–200 mesh silica
gel and 5% ethyl acetate in pet ether as an eluent to
afford 1-[2-hydroxy-4-(prop-2-yn-1-yloxy)phenyl]ethanone
EXPERIMENTAL
Commercially available reagents were used as
supplied, and all solvents were distilled prior to use.
All reactions were performed in an oven-dried
glassware. Melting points were measured in open
capillary tubes. IR spectra were recorded on a
Perkin−Elmer 337 spectrophotometer for solid samples
3
as white solid. Yield 92%, mp 196–198°C [22].
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 7 2018

SYNTHESIS AND ANTIBACTERIAL EVALUATION OF BENZOFURAN
1519
Synthesis of substituted [3-methyl-6-(prop-2-yn-
-yloxy)benzofuran-2-yl]phenylmethanones (5a–5c).
in 5 mL of aqueous DMF (50%) was added
CuSO ·5H O (5 mol %). This was followed by
1
4
2
A mixture of 1-[2-hydroxy-4-(prop-2-yn-1-yloxy)-
phenyl]ethanone 3 (2 g, 0.010 mol) with a substituted
phenacylbromide 4a–4c (0.010 mol) and K CO
addition of sodium ascorbate (10 mol %) and 4-azido-
phenol (1.2 equiv.). The reaction mixture was stirred
for 4 h at room temperature while monitoring by TLC.
After complete conversion of starting compounds, the
reaction mixture was poured over crushed ice, the
precipitate was filtered off, washed with water and
dried. The crude product was purified by washing with
ether to afford the corresponding benzofuran based
1,4-disubstituted 1,2,3-triazole analogue 7a–7c.
2
3
(
0.021 mol) was stirred in acetone (20 mL) at room
temperature for 20 h. Progress of the reaction was
monitored by TLC. After completion of the reaction,
the precipitate formed was filtered off and washed with
acetone (2 × 15 mL). The filtrate was concentrated and
the residue was purified by column chromatography
using 100–200 mesh silica gel and 10% ethyl acetate
in pet ether as an eluent to afford the corresponding
{
6-[(1-[4-Hydroxyphenyl]-1H-1,2,3-triazol-4-yl)-
methoxy]-3-methylbenzofuran-2-yl}phenylmethanone
7a). Yield 82%, grey solid, mp >300°C. IR spectrum,
substituted
[3-methyl-6-(prop-2-yn-1-yloxy)benzo-
(
furan-2-yl](phenyl)methanones 5a–5c in high yields.
–1
1
ν, cm : 3436, 1645. H NMR spectrum, δ, ppm: 9.43 s
1H), 8.10–8.02 m (3H), 7.64–7.58 m (2H), 7.56–7.50
m (3H), 7.42 s (1H), 7.21 d (J = 1.91 Hz, 1H), 7.06 d.d
J = 8.70, 2.06 Hz, 1H), 6.97 d (J = 8.84 Hz, 2H), 5.34
(
[3-Methyl-6-(prop-2-yn-1-yloxy)benzofuran-2-yl]-
phenylmethanone (5a). Yield 95%, white solid,
melting point matched with the reported earlier data
(
1
3
s (2H), 2.61 s (3H). C NMR spectrum, δ , ppm:
1
96–198°C [22].
4-Bromophenyl)[3-methyl-6-(prop-2-yn-1-yloxy)-
benzofuran-2-yl]methanone (5b). Yield 97%, white
C
1
1
85.3, 159.5, 158.1, 155.4, 148.1, 143.6, 137.9, 132.3,
29.4 (2C), 129.0, 128.2 (2C), 127.6, 123.0, 122.3
(
(
2C), 122.0, 121.5, 116.3 (2C), 114.0, 96.6, 62.2, 10.1.
–
1
solid, mp 178–180°C. IR spectrum, ν, cm : 1665
Found, %: C 70.33; H 4.48; N 9.63. C H N O .
2
5
19
3
4
1
(C=O). H NMR spectrum, δ, ppm: 7.99–7.94 m (2H),
Calculated, %: C 70.58; H 4.50; N 9.88. ESI+ mass
7
2
.69–7.65 m (2H), 7.62–7.58 m (1H), 7.12 d (J =
.16 Hz, 1H), 7.04 d.d (J = 8.68, 2.22 Hz, 1H), 4.78 d
+
spectrum: m/z: 426 [M + H] .
(
4-Bromophenyl){6-[(1-[4-hydroxyphenyl]-1H-
(
J = 2.41 Hz, 2H), 2.63 s (3H), 2.57 t (J = 2.39 Hz,
1
3
1,2,3-triazol-4-yl)methoxy]-3-methylbenzofuran-2-
1
1
1
H). C NMR spectrum, δ , ppm: 184.0, 159.0, 155.3,
C
yl}methanone (7b). Yield 85%, grey solid, mp >300°C.
48.0, 136.7, 131.5(2C), 131.2 (2C), 128.2, 127.4,
23.3, 122.1, 114.2, 96.8, 77.9, 76.2, 56.2, 10.2. Found,
–
1
1
IR spectrum, ν, cm : 3438, 1642. H NMR spectrum,
δ, ppm: 9.95 s (1H), 8.77 s (1H), 8.00 d (J = 8.57 Hz,
2H), 7.75 d (J = 8.71 Hz, 1H), 7.66 d.d (J = 8.64,
%
: C 61.66; H 3.51. C H BrO . Calculated, % C
19 13 3
+
6
1.81; H 3.55. ESI+ mass spectrum: m/z: 369 [M + H] .
4-Chlorophenyl)[3-methyl-6-(prop-2-yn-1-yloxy)-
benzofuran-2-yl]methanone (5c). Yield 90%, white
1
8
.66 Hz, 4H), 7.43 d (J = 2.00 Hz, 1H), 7.09 d.d. (J =
.71, 2.12 Hz, 1H), 6.95 d (J = 8.86 Hz, 2H), 5.33 s
(
1
3
(
2H), 2.59 s (3H). C NMR spectrum, δ , ppm: 184.0,
C
–
1
solid, mp 201-203°C. IR spectrum, ν, cm : 1669
1
1
59.5, 156.9, 155.3, 146.6, 137.5, 136.7, 131.5 (2C),
29.0, 128.7 (2C), 127.1, 122.7, 122.1, 122.0, 121.5
1
(
7
(
C=O). H NMR spectrum, δ, ppm: 8.07–8.02 m (2H),
.59 t (J = 6.74 Hz, 1H), 7.53–7.47 m (2H), 7.12 d
J = 2.13 Hz, 1H), 7.03 d.d (J = 8.72, 2.22 Hz, 1H),
(
2C), 116.4 (2C), 113.9, 96.7, 62.1, 10.0. Found, %: C
5
5
9.36; H 15.62; N 8.30. C H N O . Calculated, %: C
25 19 3 4
4
2
1
.78 d (J = 2.37 Hz, 2H), 2.63 s (3H), 2.57 t (J =
9.54; H 15.84; N 8.33. ESI+ mass spectrum: m/z: 505
1
3
+
.38 Hz, 1H). C NMR spectrum, δ , ppm: 183.9,
C
[M + H] .
59.0, 155.3, 148.1, 138.7, 136.2, 131.1 (2C), 128.6
(
4-Chlorophenyl){6-[(1-[4-hydroxyphenyl]-1H-
(
1
2C), 128.2, 123.3, 122.0, 114.2, 96.8, 77.9, 76.2, 56.2,
0.2. Found, %: C 70.03; H 3.98. C H ClO . Cal-
1
,2,3-triazol-4-yl)methoxy]-3-methylbenzofuran-2-
19
13
3
yl}methanone (7c). Yield 82%, grey solid, mp >300°C.
culated, %: C 70.27; H 4.03. ESI+ mass spectrum: m/z:
–
1
1
+
IR spectrum, ν, cm : 3441, 1641 (C=O). H NMR
spectrum, δ, ppm: 9.97 s (1H), 8.82 s (1H), 8.02 d
(J = 8.58 Hz, 2H), 7.79 d (J = 8.72 Hz, 1H), 7.67 d.d
(J = 8.64, 1.66 Hz, 4H), 7.50 d (J = 2.00 Hz, 1H), 7.11
d.d (J = 8.73, 2.12 Hz, 1H), 6.94 d (J = 8.88 Hz, 2H),
3
25 [M + H] .
Synthesis of substituted {6-[(1-[4-hydroxyphenyl]-
H-1,2,3-triazol-4-yl)methoxy]-3-methylbenzofuran-
-yl}phenylmethanones (7a–7c). To a solution of a
1
2
13
substituted [3-methyl-6-(prop-2-yn-1-yloxy)benzo-
5.32 s (2H), 2.57 s (3H). C NMR spectrum, δ , ppm:
C
furan-2-yl]phenylmethanone 5a–5c (500 mg, 1 equiv.)
183.1, 159.7, 157.8, 155.1, 147.1, 137.4, 136.2, 131.0
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 7 2018

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520
SUNITHA et al.
(
1
%
%
2C), 128.6, 128.5 (2C), 127.7, 122.9, 122.4, 122.1,
22.0 (2C), 116.0 (2C), 114.4, 96.6, 61.6, 9.9. Found,
(4-Chlorophenyl){3-methyl-6-[(1-[4-(prop-2-yn-
1-yloxy)phenyl]-1H-1,2,3-triazol-4-yl)methoxy]benzo-
furan-2-yl}methanone (8c). Yield 92%, white solid,
mp >300°C. IR spectrum, ν, cm : 1640 (C=O). H NMR
spectrum, δ, ppm: 8.16–8.08 m (2H), 8.05 s (1H), 7.77–
: C 65.05; H 7.65; N 9.03. C H ClN O . Calculated,
25 18 3 4
–1
1
: C 65.29; H 7.71; N 9.14. ESI+ mass spectrum:
+
m/z: 460 [M + H] .
7
1
.69 m (2H), 7.60–7.51 m (3H), 7.17 d (J = 2.12 Hz,
H), 7.15–7.10 m (2H), 7.08–7.04 m (1H), 5.36 s
Synthesis of substituted {3-methyl-6-[(1-[4-(prop-
-yn-1-yloxy)phenyl]-1H-1,2,3-triazol-4-yl)methoxy]-
2
(
2
2H), 4.77 d (J = 2.37 Hz, 2H), 2.63 s (3H), 2.58 t (J =
.37 Hz, 1H). Found, %: C 67.33; H 4.00; N 8.28.
C H ClN O . Calculated, %: C 67.54; H 4.05; N
benzofuran-2-yl}phenylmethanones (8a–8c). To a
well stirred mixture of a substituted {6-[(1-[4-hydroxy-
phenyl]-1H-1,2,3-triazol-4-yl)methoxy]-3-methylbenzo-
furan-2-yl}(phenyl)methanone 7a–7c (500 mg, 1 equiv.)
dissolved in dry DMF was added NaH (1 equiv.). Then
propargyl bromide 80% in toluene (1.2 equiv.) was
added drop wise and the reaction mixture was stirred
for ca 1 h at room temperature. Progress of the reaction
was monitored by TLC. The reaction mixture was
quenched with ice cooled water, the solid precipitate
was filtered off, washed with water and dried. The
crude product was purified by washing with hexane
and ether to afford the corresponding substituted
2
8
20
3
4
+
8
.44. ESI+ mass spectrum: m/z: 498 [M + H] .
Synthesis of {6-[(1-[4-([1-hexyl-1H-1,2,3-triazol-
4-yl]methoxy)phenyl]-1H-1,2,3-triazol-4-yl)methoxy]-
3-methylbenzofuran-2-yl}phenylmethanone (10a–10l).
To a well stirred solution of a substituted {3-methyl-6-
[(1-[4-(prop-2-yn-1-yloxy)phenyl]-1H-1,2,3-triazol-4-
yl)methoxy]benzofuran-2-yl}(phenyl)methanone (8a–
8c) (100 mg, 1 equiv.) in 5 mL of aqueous DMF (50%)
was added CuSO ·5H O (5 mol %) followed by
sodium ascorbate (10 mol %) and an azide (1.2 equiv.).
The reaction mixture was stirred for 4 h at room
temperature (monitored by TLC). After complete
conversion of starting compounds the reaction mixture
was poured over crushed ice. The solid precipitate was
filtered off, washed with water and dried. The crude
product was purified by washing with ether to afford
the corresponding 3-methyl-6-{[1-(4-[(1-phenyl-1H-
4
2
{
3-methyl-6-[(1-[4-(prop-2-yn-1-yloxy)phenyl]-1H-1,2,3-
triazol-4-yl)methoxy]benzofuran-2-yl}(phenyl)methanone
a–8c.
8
{
3-Methyl-6-[(1-[4-(prop-2-yn-1-yloxy)phenyl]-
1
H-1,2,3-triazol-4-yl)methoxy]benzofuran-2-yl}-
phenylmethanone (8a). Yield 95%, white solid, mp
–
1
1
>
300°C. IR spectrum, ν, cm : 1642 (C=O). H NMR
1
,2,3-triazol-4-yl]methoxy)phenyl]-1H-1,2,3-triazol-4-
spectrum, δ, ppm: 8.09–8.04 m (2H), 8.02 s (1H), 7.69–
.64 m (2H), 7.61–7.49 m (4H), 7.18 d (J = 2.11 Hz,
H), 7.14–7.09 m (2H), 7.08–7.03 m (1H), 5.35 s
yl)methoxy]benzofuran-2-yl}phenylmethanone 10a–10l.
7
1
(
2
1
1
1
5
{6-[(1-[4-([1-Hexyl-1H-1,2,3-triazol-4-yl]methoxy)-
phenyl]-1H-1,2,3-triazol-4-yl)methoxy]-3-methyl-
benzofuran-2-yl}phenylmethanone (10a). Yield 94%,
white solid, mp >300°C. IR spectrum, ν, cm : 1642
(C=O). H NMR spectrum, δ, ppm: 8.10 s (1H), 8.08–
8.02 s (3H), 7.67–7.62 m (2H), 7.55–7.44 m (4H), 7.22–
7.19 m (1H), 7.14–7.10 m (2H), 7.09–7.04 m (1H),
5.38 s (2H), 5.26 s (2H), 4.37 t (J = 7.27 Hz, 2H), 2.68
s (3H), 1.98–1.88 m (2H), 1.31 d (J = 10.93 Hz, 6H),
0
1
1
2H), 4.75 d (J = 2.39 Hz, 2H), 2.61 s (3H), 2.57 t (J =
1
3
.38 Hz, 1H). C NMR spectrum, δ , ppm: 185.4,
C
–
1
59.5, 157.7, 155.5, 148.3, 144.1, 138.0, 132.4, 131.0,
29.6 (2C), 128.3 (2C), 127.6, 123.2, 122.2 (2C),
22.0, 121.3, 115.8 (2C), 114.0, 96.7, 77.8, 76.2, 62.4,
6.1, 10.2. Found, %: C 72.35; H 4.43; N 9.01.
1
C H N O . Calculated, %: C 72.56; H 4.57; N 9.07.
2
8
21
3
4
+
ESI+ mass spectrum: m/z: 464 [M + H] .
4-Bromophenyl){3-methyl-6-[(1-[4-(prop-2-yn-
-yloxy)phenyl]-1H-1,2,3-triazol-4-yl)methoxy]benzo-
furan-2-yl}methanone (8b). Yield 86%, white solid,
13
.88 t (J = 6.86 Hz, 3H). C NMR spectrum, δ , ppm:
C
(
85.3, 159.4, 157.9, 155.4, 148.2, 144.3, 138.0, 132.3,
30.7, 129.7 (2C), 128.7 (2C), 127.6, 126.5, 125.8,
1
–
1
1
123.3, 122.3 (2C), 121.3, 119.6, 116.3, (2C), 114.1,
6.8, 62.6, 56.0, 50.5, 31.2, 30.1, 26.3, 22.3, 13.8, 10.2.
Found, %: C 68.96; H 5.77; N 14.18. C H N O .
mp >300°C. IR spectrum, ν, cm : 1643 (C=O). H
NMR spectrum, δ, ppm: 8.10–8.04 m (2H), 7.98 s
9
3
4
34
6
4
(
(
(
(
1H), 7.71–7.65 m (2H), 7.60–7.49 m (4H), 7.20 d
J = 2.14 Hz, 1H), 7.15–7.09 m (2H), 7.10–7.04 m
1H), 5.36 s (2H), 4.74 d (J = 2.36 Hz, 2H), 2.62 s
3H), 2.56 t (J = 2.37 Hz, 1H). Found, %: C 61.82; H
Calculated, %: C 69.14; H 5.80; N 14.23. ESI+ mass
spectrum: m/z: 591 [M + H] .
+
{3-Methyl-6-[(1-[4-([1-octyl-1H-1,2,3-triazol-4-
yl]methoxy)phenyl]-1H-1,2,3-triazol-4-yl)methoxy]-
benzofuran-2-yl}phenylmethanone (10b). Yield
3
.66; N 7.58. C H BrN O . Calculated, %: C 62.00;
28 20 3 4
+
H 3.72; N 7.75. ESI+ mass spectrum: m/z: 543 [M + H] .
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 7 2018

SYNTHESIS AND ANTIBACTERIAL EVALUATION OF BENZOFURAN
1521
–
1
9
1
8
5%, white solid, mp >300°C. IR spectrum, ν, cm :
ppm: 8.14 s (1H), 8.09–8.03 m (2H), 8.00 s (1H), 7.75
d (J = 8.71 Hz, 1H), 7.66 d.d (J = 8.64, 1.66 Hz, 4H),
7.43 d (J = 2.00 Hz, 1H), 7.09 d.d (J = 8.71, 2.12 Hz,
1H), 6.95 d (J = 8.86 Hz, 2H), 5.37 s (2H), 5.25 s
(2H), 4.36 t (J = 7.28 Hz, 2H), 2.66 s (3H), 1.99–1.87
1
640 (C=O). H NMR spectrum, δ, ppm: 8.12 s (1H),
.09–8.02 s (3H), 7.69–7.63 m (2H), 7.57–7.45 m
(
4H), 7.20–7.18 m (1H), 7.15–7.10 m (2H), 7.09–7.04
m (1H), 5.36 s (2H), 5.25 s (2H), 4.37 t (J = 6.48 Hz,
H), 2.67 s (3H), 1.99–1.84 m (2H), 1.39–1.18 m
10H), 0.96–0.79 m (3H). C NMR spectrum, δC,
ppm: 185.5, 159.7, 157.6, 155.7, 148.3, 144.5, 138.1,
32.5, 130.6, 129.8 (2C), 128.8 (2C), 127.8, 126.5,
25.8, 123.4, 122.4 (2C), 121.3, 119.7, 116.3, (2C),
14.1, 96.7, 62.6, 56.0, 50.5, 31.7, 30.2, 29.0, 28.9,
6.5, 22.6, 14.0, 10.1. Found, %: C 57.34; H 3.20; N
.96. C H N O . Calculated, %: C 57.44; H 3.28; N
2
(
m (2H), 1.33 d (J = 10.93 Hz, 6H), 0.89 t (J = 6.86
1
3
13
Hz, 3H). C NMR spectrum, δ , ppm: 184.9, 159.5,
C
157.8, 155.6, 148.5, 144.5, 135.1, 133.5 (2C), 131.4
(2C), 129.5, 128.6, 127.5, 126.3, 125.9, 123.5, 122.5
(2C), 121.3, 119.6, 116.5, (2C), 114.1, 96.7, 62.4,
56.1, 50.7, 31.1, 30.1, 26.3, 22.4, 13.7, 10.1. Found,
%: C 60.71; H 4.92; N 12.39. C H BrN O .
1
1
1
2
7
8
3
4
33
6
4
Calculated, %: C 60.99; H 4.97; N 12.55. ESI+ mass
3
6
38
6
4
+
+
.04. ESI+ mass spectrum: m/z: 619 [M + H] .
spectrum: m/z: 669 [M + H] .
(
4-Bromophenyl){3-methyl-6-[(1-[4-([1-octyl-1H-
{
3-Methyl-6-[(1-[4-([1-octyl-1H-1,2,3-triazol-4-
1
4
,2,3-triazol-4-yl]methoxy)phenyl]-1H-1,2,3-triazol-
-yl)methoxy]benzofuran-2-yl}methanone (10f).
yl]methoxy)phenyl]-1H-1,2,3-triazol-4-yl)methoxy]
benzofuran-2-yl}phenylmethanone (10c). Yield
0%, white solid, mp >300°C. IR spectrum, ν, cm :
–
1
Yield 93%, white solid, mp >300°C. IR spectrum, ν,
9
1
8
7
7
(
1
1
(
–
1
1
1
cm : 1656 (C=O). H NMR spectrum, δ, ppm: 8.12 s
1H), 8.08–8.02 m (2H), 8.01 s (1H), 7.77 d (J =
.71 Hz, 1H), 7.67 d.d (J = 8.66, 1.67 Hz, 4H), 7.45 d
J = 2.00 Hz, 1H), 7.10 d.d (J = 8.71, 2.12 Hz, 1H),
6.96 d (J = 8.86 Hz, 2H), 5.36 s (2H), 5.27 s (2H),
.35 t (J = 6.48 Hz, 2H), 2.68 s (3H), 1.98–1.85 m
643 (C=O). H NMR spectrum, δ, ppm: 8.12 s (1H),
(
8
(
.09–8.04 m (2H), 8.01 s (1H), 7.69–7.63 m (2H), 7.51–
.43 m (9H), 7.20–7.17 m (1H), 7.14–7.10 m (2H),
.08–7.04 m (1H), 5.38 s (2H), 5.26 s (2H), 2.68 s
3H). C NMR spectrum, δ , ppm: 185.4, 159.4, 157.8,
55.3, 148.1, 144.1, 138.0, 136.0 (2C), 132.3, 130.8,
29.5 (2C), 128.5 (2C), 127.6, 126.5, 125.9, 123.2, 122.2
2C), 122.0, 121.3, 120.8, 120.0 (2C), 119.6, 116.2, (2C),
14.1, 96.8, 62.6, 56.0, 10.2. Found, %: C 57.34; H 3.20;
N 7.96. C H N O . Calculated, %: C 57.44; H 3.28; N
13
C
4
(
1
3
2H), 1.38–1.17 m (10H), 0.98–0.79 m (3H). C NMR
spectrum, δ , ppm: 184.9, 159.5, 157.8, 155.6, 148.5,
C
1
1
44.5, 135.1, 133.5 (2C), 131.4 (2C), 129.5, 128.6,
27.5, 126.3, 125.9, 123.5, 122.5 (2C), 121.3, 119.6,
116.5, (2C), 114.1, 96.7, 62.5, 56.1, 50.6, 31.8, 30.3,
9.1, 28.8, 26.7, 22.6, 14.1, 10.2. Found, %: C 61.72;
H 5.29; N 11.95. C H BrN O . Calculated, %: C
1
34
26
6
4
+
8
.04. ESI+ mass spectrum: m/z: 583 [M + H] .
2
{6-[(1-[4-([1-(4-Chlorophenyl)-1H-1,2,3-triazol-4-
3
6
37
6
4
yl]methoxy)phenyl]-1H-1,2,3-triazol-4-yl)methoxy]-
-methylbenzofuran-2-yl}phenylmethanone (10d).
Yield 86%, white solid, mp >300°C. IR spectrum, ν,
61.98; H 5.35; N 12.05. ESI+ mass spectrum: m/z: 697
[M + H] .
+
3
(
4-Bromophenyl){3-methyl-6-[(1-[4-([1-octyl-1H-
–
1
1
cm : 1640 (C=O). H NMR spectrum, δ, ppm: 8.14 s
1
4
,2,3-triazol-4-yl]methoxy)phenyl]-1H-1,2,3-triazol-
-yl)methoxy]benzofuran-2-yl}methanone (10g).
(
(
1H), 8.08–8.03 m (2H), 8.02 s (1H), 7.69–7.63 m
2H), 7.57–7.48 m (9H), 7.14–7.10 m (2H), 7.08–7.04
Yield 88%, white solid, mp >300°C. IR spectrum, ν,
13
m (1H), 5.34 s (2H), 5.25 s (2H), 2.67 s (3H).
C
–1
1
cm : 1641 (C=O). H NMR spectrum, δ, ppm: 8.12 s
NMR spectrum, δ , ppm: 184.8, 158.9, 157.4, 154.9,
C
(
(
1H), 8.09–8.04 m (2H), 8.01 s (1H), 7.69–7.63 m
1
48.0, 144.2, 138.1, 135.8 (2C), 134.9, 130.5, 129.5
2H), 7.51–7.43 m (9H), 7.14–7.10 m (2H), 7.08–7.04
(
(
(
2C), 128.4 (2C), 127.6, 126.5, 125.7, 123.1, 122.3
2C), 122.1, 121.3, 120.8, 120.1 (2C), 119.7, 116.3,
2C), 114.2, 96.8, 62.7, 56.1, 10.1. Found, %: C 65.86;
13
m (1H), 5.38 s (2H), 5.26 s (2H), 2.68 s (3H).
C
NMR spectrum, δ , ppm: 185.5, 159.2, 157.5, 155.4,
C
148.3, 144.4, 138.1, 136.0, 132.3, 130.8, 133.4 (2C),
131.5 (2C), 129.5, 128.5 (2C), 127.6, 126.5, 125.9, 123.2,
122.2 (2C), 122.1, 121.3, 120.8, 120.1 (2C), 119.7, 116.2,
H 4.01; N 13.47. C H ClN O . Calculated, %: C 66.18;
3
4
25
6
4
+
H 4.08; N 13.62. ESI+ mass spectrum: m/z: 502 [M + H] .
(
3
3
2C), 114.1, 96.8, 62.6, 56.0, 10.1. Found, %: C 61.55; H
(
4-Bromophenyl){6-[(1-[4-([1-(4-chlorophenyl)-
.75; N 12.67. C H BrN O . Calculated, %: C 61.73; H
34 25 6 4
1
H-1,2,3-triazol-4-yl]methoxy)phenyl]-1H-1,2,3-tri-
azol-4-yl)methoxy]-3-methylbenzofuran-2-yl}metha-
+
.81; N 12.70. ESI+ mass spectrum: m/z 661 [M + H] .
none (10e). Yield 90%, white solid, mp >300°C. IR
spectrum, ν, cm : 1654 (C=O). H NMR spectrum, δ,
(4-Bromophenyl){6-[(1-[4-([1-(4-chlorophenyl)-
1H-1,2,3-triazol-4-yl]methoxy)phenyl]-1H-1,2,3-
–
1
1
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 7 2018

1
522
SUNITHA et al.
triazol-4-yl)methoxy]-3-methylbenzofuran-2-yl}-
12.55. C36
H37ClN O . Calculated, %: C 66.20; H 5.71;
6 4
+
methanone (10h). Yield 94%, white solid, mp >300°C.
N 12.87. ESI+ mass spectrum: m/z: 653 [M + H] .
–
1
1
IR spectrum, ν, cm : 1642 (C=O). H NMR spectrum,
δ, ppm: 8.14 s (1H), 8.10–8.04 m (2H), 8.03 s (1H),
(
4-Chlorophenyl){3-methyl-6-[(1-[4-([1-octyl-1H-
1,2,3-triazol-4-yl]methoxy)phenyl]-1H-1,2,3-triazol-
7
.67–7.61 m (4H), 7.58–7.49 m (6H), 7.19–7.14 m
4
-yl)methoxy]benzofuran-2-yl}methanone (10k).
(
2H), 7.10–7.05 m (1H), 5.37 s (2H), 5.25 s (2H), 2.66
Yield 84%, white solid, mp >300°C. IR spectrum, ν,
1
3
s (3H). C NMR spectrum, δ , ppm: 185.3, 158.9,
–1
1
C
cm : 1641 (C=O). H NMR spectrum, δ, ppm: 8.13 s
1
1
1
1
6
57.9, 155.6, 147.8, 144.6, 138.9, 136.1,134.3, 132.4,
30.6, 133.4 (2C), 131.5 (2C), 129.5, 128.8 (2C),
27.6, 126.5, 125.9, 123.2, 122.2 (2C), 122.1, 121.3,
20.8, 120.1 (2C), 119.7, 116.2, (2C), 114.3, 96.6,
2.6, 56.0, 10.1. Found, %: C 58.42; H 3.27; N 11.86.
(
(
1H), 8.10–8.05 m (2H), 8.02 s (1H), 7.67–7.62 m
2H), 7.52–7.43 m (9H), 7.15–7.10 m (2H), 7.09–7.03
13
m (1H), 5.37 s (2H), 5.27 s (2H), 2.67 s (3H). C NMR
spectrum, δ , ppm: 185.7, 159.4, 157.6, 155.7, 148.5,
C
144.6, 138.3, 136.1, 132.3, 130.8, 133.4 (2C), 131.5
C H BrClN O . Calculated, %: C 58.68; H 3.48; N
3
4
24
6
4
(2C), 129.5, 128.5 (2C), 127.6, 126.5, 125.9, 123.2,
+
1
2.08. ESI+ mass spectrum: m/z: 695 [M + H] .
1
1
6
22.2 (2C), 122.1, 121.3, 120.8, 120.1 (2C), 119.7,
16.2, (2C), 114.1, 96.8, 62.7, 56.1, 10.2. Found, %: C
5.91; H 5.70; N 13.45. C H ClN O . Calculated, %:
(
4-Chlorophenyl){6-[(1-[4-([1-(4-chlorophenyl)-
1
H-1,2,3-triazol-4-yl]methoxy)phenyl]-1H-1,2,3-
34 25
6
4
C 66.18; H 5.75; N 13.62. ESI+ mass spectrum: m/z:
triazol-4-yl)methoxy]-3-methylbenzofuran-2-yl}
+
6
17 [M + H] .
4-Chlorophenyl){6-[(1-[4-([1-(4-chlorophenyl)-
H-1,2,3-triazol-4-yl]methoxy)phenyl]-1H-1,2,3-
methanone (10i). Yield 95%, white solid, mp >300°C.
–
1
1
IR spectrum, ν, cm : 1639 (C=O). H NMR spectrum,
δ, ppm: 8.12 s (1H), 8.10–8.04 m (2H), 8.02 s (1H),
(
1
7
4
2
5
1
6
1
1
.76 d (J = 8.72 Hz, 1H), 7.67 d.d (J = 8.66, 1.66 Hz,
H), 7.46 d (J = 2.00 Hz, 1H), 7.09 d.d (J = 8.72,
.12 Hz, 1H), 6.97 d (J = 8.88 Hz, 2H), 5.38 s (2H),
.26 s (2H), 4.37 t (J = 7.28 Hz, 2H), 2.67 s (3H), 1.98–
.88 m (2H), 1.35 d (J = 10.93 Hz, 6H), 0.88 t (J =
triazol-4-yl)methoxy]-3-methylbenzofuran-2-yl}-
methanone (10l). Yield 88%, white solid, mp >300°C.
–
1
1
IR spectrum, ν, cm : 1639 (C=O). H NMR spectrum,
δ, ppm: 8.12 s (1H), 8.08–8.03 m (2H), 8.01 s (1H),
7
.68–7.62 m (4H), 7.57–7.46 m (6H), 7.17–7.16 m
13
.86 Hz, 3H). C NMR spectrum, δ , ppm: 185.4,
C
(2H), 7.11–7.06 m (1H), 5.36 s (2H), 5.24 s (2H), 2.67
13
59.7, 157.5, 155.8, 148.6, 144.7, 138.5, 131.4 (2C),
29.5, 128.6 (2C), 127.5, 126.3, 125.9, 123.5, 122.5
s (3H). C NMR spectrum, δ , ppm: 185.4, 158.7,
C
157.7, 155.7, 147.6, 144.6, 138.7, 136.2, 134.3, 132.4,
130.6, 133.4 (2C), 131.5 (2C), 129.5, 128.8 (2C), 127.6,
126.5, 125.9, 123.2, 122.2 (2C), 122.1, 121.3, 120.8,
(2C), 121.3, 119.6, 116.5, (2C), 114.1, 96.7, 62.4, 56.1,
5
6
0.6, 31.3, 30.2, 26.4, 22.6, 13.5, 10.2. Found, %: C
5.08; H 5.48; N 13.22. C H ClN O . Calculated, %:
34
33
6
4
120.1 (2C), 119.7, 116.2, (2C), 114.3, 96.6, 62.8 56.3,
0.2. Found, %: C 62.45; H 3.66; N 12.78.
C H Cl N O . Calculated, %: C 62.68; H 3.71; N
C 65.33; H 5.32; N 13.44. ESI+ mass spectrum: m/z:
1
+
625 [M + H] .
3
4
24
2
6
4
+
1
2.90. ESI+ mass spectrum: m/z: 652 [M + H] .
(
4-Chlorophenyl){3-methyl-6-[(1-[4-([1-octyl-1H-
1,2,3-triazol-4-yl]methoxy)phenyl]-1H-1,2,3-triazol-
Antibacterial activity. Bacterial strains. The gram-
4
-yl)methoxy]benzofuran-2-yl}methanone (10j).
positive strains Micrococcus luteus (ATCC 10240),
methicillin-resistant Staphylococcus aureus (MRSA,
NCTC 13616), Bacillus subtilis (ATCC 6633), and
Bacillus cereus (ATCC 14579) and the gram-negative
strains Pseudomonas aeruginosa (ATCC 27853),
Klebsiella pneumoniae (ATCC 43816), Escherichia
coli (ATCC 8739), and Proteus vulgaris (ATCC
13315) were purchased from the American Type
Culture Collection. Methicillin-resistant Staphylococcus
aureus was purchased from the Public Health England
Culture Collections. All bacterial strains, stored at
‒80°C, were streaked on Luria‒Bertani (LB) agar
plates (Hi-media Laboratories, Mumbai, India) and
incubated at 37°C for 20−24 h. A few isolated colonies
Yield 94%, white solid, mp >300°C. IR spectrum, ν,
–
1
1
cm : 1645 (C=O). H NMR spectrum, δ, ppm: 8.14 s
1H), 8.09–8.03 m (2H), 8.01 s (1H), 7.75 d (J = 8.74 Hz,
(
1
2
H), 7.64 d.d (J = 8.64, 1.68 Hz, 4H), 7.45 d (J =
.01 Hz, 1H), 7.10 d.d (J = 8.73, 2.11 Hz, 1H), 6.98 d
(
J = 8.89 Hz, 2H), 5.37 s (2H), 5.28 s (2H), 4.36 t (J =
6
1
.47 Hz, 2H), 2.67 s (3H), 1.98–1.86 m (2H), 1.38–
1
3
.18 m (10H), 0.98–0.79 m (3H). C NMR spectrum,
δC, ppm: 185.5, 159.8, 157.6, 155.9, 148.7, 144.8,
1
1
1
2
38.7, 131.5 (2C), 129.6, 128.7 (2C), 127.6, 126.4,
25.8, 123.5, 122.5 (2C), 121.3, 119.6, 116.5, (2C),
14.1, 96.7, 62.4, 56.2, 50.5, 31.7, 30.4, 29.3, 28.7,
6.7, 22.5, 14.2, 10.1. Found, %: C 66.01; H 5.66; N
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 7 2018

SYNTHESIS AND ANTIBACTERIAL EVALUATION OF BENZOFURAN
were selected from each plate and suspended in 5 mL
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