Synthesis and biological evaluation of novel benzoquinones as potential antimicrobial agents

Article abstract of DOI:10.1007/s00044-012-0076-0

New series of 2,5-dihydroxyphenyl-1,3-thiazoles 4a-l was synthesized by reacting 2,5-dihydroxyphenacyl bromide with various 4-aryl thiosemicarbazones 3a-l that on oxidation with ferric chloride yielded the corresponding N ¹-substituted benzylid

Full text of DOI:10.1007/s00044-012-0076-0

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2013) 22:841–851
DOI 10.1007/s00044-012-0076-0
ORIGINAL RESEARCH
Synthesis and biological evaluation of novel benzoquinones
as potential antimicrobial agents
•
Ibrahim Chaaban El Sayeda M. El Khawass
•
•
Mona A. Mahran Heba A. Abd El Razik
•
•
Nehad S. El Salamouni Abeer E. Abdel Wahab
Received: 17 September 2011 / Accepted: 20 April 2012 / Published online: 13 May 2012
Ó Springer Science+Business Media, LLC 2012
Abstract New series of 2,5-dihydroxyphenyl-1,3-thiazoles
4a–l was synthesized by reacting 2,5-dihydroxyphenacyl
bromide with various 4-aryl thiosemicarbazones 3a–l that
on oxidation with ferric chloride yielded the corresponding
N1-substituted benzylidene-N2-[3-aryl-4-(1,4-benzoquinon-
2-yl)-1,3-thiazol-2-ylidene]hydrazines 5a–l. They were eval-
uated for antibacterial activity against Staphylococcus aureus
and Bacillus subtilis as Gram-positive bacteria, Escherichia
coli and Pseudomonas aeruginosa as Gram-negative bacteria.
They were also evaluated for their in vitro antifungal potential
against Candida albicans. Almost all tested compounds were
found to possess variable degrees of antimicrobial activity.
The obtained data revealed that compounds 4b–h and 5e, 5f
and 5l exhibited promising antimicrobial activity against the
testedorganismsofwhichcompound4b provedtobethemost
active.
Keywords Hydroquinones Á Benzoquinones Á Thiazoles Á
Antibacterial activity Á Antifungal activity
Introduction
The incidence of fungal and bacterial infections has dra-
matically increased. The widespread use of antifungal and
antibacterial drugs together with resistance of fungal and
bacterial infections to antimicrobial agents has led to
serious health hazards. This has initiated discovery and
modification of new antifungal and antibacterial drugs
(Parmar et al., 2011; Kaplancikli et al., 2004).
Hydroquinones and quinones are of current interest
because of their wide-spectrum bioactivity and chemo-
therapeutic value. Several quinone and hydroquinone
derivatives exhibit antibacterial and antifungal activities
(Tandon et al., 2005, 2006; Hammam et al., 2007; Batra et
al., 2008; Tandon et al., 2009; Ryu et al., 2009). In addi-
tion, several naturally occurring quinones and hydro-
quinones such as avarol, avarone, hydroxysesamone,
2,3-epoxysesamone, and newbouldiaquinone were reported
as potent antimicrobial agents (Cariello et al., 1982; Seibert
et al., 1985; Kondracki and Guyot, 1989; Feroj Hasan
et al., 2001; Machado et al., 2003; Eyong et al., 2006).
Furthermore, kalafungin, grantican B, nanaomycins, and
griseusins A and B are members of a family of naturally
occurring antibiotics containing a quinone ring (Johnson
and Dietz, 1968; Tsuji et al., 1976).
This study was presented in the International Conference on
Antimicrobial Research, Valladolid—Spain, November 3–5, 2010.
I. Chaaban Á E. S. M. El Khawass Á M. A. Mahran Á
H. A. Abd El Razik (&) Á N. S. El Salamouni
Department of Pharmaceutical Chemistry, Faculty of Pharmacy,
Alexandria University, Alexandria 21521, Egypt
e-mail: heba_attia75@yahoo.com
M. A. Mahran
Department of Pharmaceutical Chemistry, Faculty of Pharmacy,
King Abdulaziz University, Jeddah, Saudi Arabia
The 1,3-thiazole heterocycle is an interesting building
block in a variety of natural and synthetic compounds
found to possess good antibacterial potential (Sadek et al.,
2011). In addition, literature survey revealed that thiazole
ring systems have occupied a unique position in the design
and synthesis of novel biologically active agents with
A. E. Abdel Wahab
Medical Biotechnology Department, Genetic Engineering and
Biotechnology Research Institute (GEBRI), City for Scientific
Research and Technology Application (Previously Mubarak City
for Scientific Research and Technology Application),
Borg El-Arab, Alexandria, Egypt
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Med Chem Res (2013) 22:841–851
remarkable antimicrobial activity (Turan-Zitouni et al.,
2002; Ryu et al., 2003; Bonde and Gaikwad, 2004; Shih
and Ke, 2004; Bondock et al., 2007; Karegoudar et al.,
2008). In view of the aforementioned properties and as a
continuation of an ongoing program aiming at the synthesis
of new quinones and hydroquinones with antimicrobial
activity, in this article, we have reported the synthesis of
some new hydroquinones and benzoquinones connected to
thiazolines-bearing methoxy groups based on the fact that
incorporation of alkoxy substituents would result in
enhancement of several biological activities because of the
magnification of compound’s lipophilicity (Barboni et al.,
2006; Lin et al., 2005).
1a–d and the appropriate aryl thiosemicarbazide 2a–c in
ethanol while stirring at room temperature. It is to be noted
down that the thiosemicarbazones 3a–g and 3k were pre-
pared following previously published reaction conditions
ˇ
(Das and Rout, 1955; Tisler, 1956; Chaaban et al., 2006;
Cunha and da Silva, 2009; de Aquino et al., 2008). The
4-aryl-1-substituted benzylidene thiosemicarbazides 3a–
l were allowed to react with an equimolar amount of 2,5-
dihydroxyphenacyl bromide in 99.9 % ethanol in the pres-
ence of anhydrous sodium acetate to afford the target
thiazolines 4a–l. Oxidationof thelatter compounds with cold
20 % aqueous ferric chloride solution in dimethylformamide
afforded the corresponding quinones 5a–l.
Results and discussion
In vitro antibacterial and antifungal activities
Chemistry
Dimethylsulfoxide (DMSO) was used as blank and showed
no activity. All the newly synthesized compounds were
evaluated for their in vitro antibacterial activity against
Staphylococcus aureus and Bacillus subtilis as Gram-
positive bacteria, Escherichia coli and Pseudomonas
aeruginosa as Gram-negative bacteria. They were also
evaluated for their in vitro antifungal potential against
Candida albicans. Their inhibition zones were measured
by the cup-diffusion technique (Jain and Kar, 1971) and
further evaluation was carried out to determine their min-
imum inhibitory concentration (MIC) by the twofold serial
dilution method (Scott, 1989). Ampicillin was used as
standard antibacterial, while Clotrimazole was used as
antifungal reference.
Synthesis of the intermediates and target compounds was
accomplished according to the steps illustrated in Scheme 1.
Acetylation of hydroquinone with acetic anhydride in the
presence of drops of concentrated sulfuric acid afforded
hydroquinone diacetate (Prichard, 1948). It was then sub-
jected to Fries rearrangement using anhydrous aluminum
chloride at 160–165 °C yielding 2,5-dihydroxyacetophe-
none (Amin and Shah, 1948). 2,5-Dihydroxyphenacyl
bromide was prepared by reacting a suspension of 2,5-
dihydroxyacetophenone with freshly prepared cupric bro-
mide in ethyl acetate/chloroform mixture according to the
reported method (King and Ostrum, 1964). The thiosemi-
carbazone derivatives 3a–l were prepared by the condensa-
tion of equimolar amounts of the appropriate aldehyde
Antimicrobial screening of the thiazoline hydroquinones
4a–l and their corresponding quinone derivatives
R1
O
R1
H
H
N
H
N
Scheme 1 Synthesis of
intermediate and target
compounds
H
N
H
N
ethanol
rt
H
H2N
N
+
S
S
R2
R2
R
R
R3
1a-d
R3
3a-l
2a-c
OH
O
ethanol
NaOAc
Br
OH
R1
R1
R2
R3
R2
R3
O
O
OH
OH
S
S
N
N
FeCl3
N
N
R
N
N
4a-l
5a-l
R
R = H, CH3, Cl
R1 = H, OCH3
R2, R3 = H, OH, OCH3
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Med Chem Res (2013) 22:841–851
843
5a–l revealed that most of them possess potent antimicro-
bial activity, whereas few show antifungal potency.
antimicrobial activity, whereas its oxidation to 5k
increased the activity against P. aeruginosa to be equal to
that of Ampicillin. Finally, compound 4l (R = Cl, R1 = H,
R2 = OCH3, R3 = OH) showed moderate activity against
S. aureus and C. albicans, whereas oxidation to quinone 5l
increased the activity against B. subtilis, E. coli, and
C. albicans to about half that of references also activity
against P. aeruginosa increased to be equal to that of
Ampicillin, whereas activity against S. aureus was reduced
to its half.
Compound 4a (R, R1, R3 = H, R2 = OCH3) elicited
equipotent activity to Ampicillin against P. aeruginosa,
whereas its oxidation to the quinone 5a maintained same
activity against P. aeruginosa and increased activity
against E. coli. Compound 4b (R, R2 = H, R1, R3 =
OCH3) was almost equipotent to Ampicillin against
B. subtilis and E. coli as well as four times more potent
against P. aeruginosa. Oxidation of 4b to the correspond-
ing quinone 5b decreased the antimicrobial activity against
B. subtilis, E. coli, and P. aeruginosa. Furthermore, com-
pound 4c (R, R1 = H, R2 = OH, R3 = OCH3) revealed
nearly half the activity of reference drugs against S. aureus
and C. albicans, whereas it showed nearly equal activity
against E. coli and P. aeruginosa. Oxidation of 4c to the
corresponding quinone 5c reduced activity against all
organisms. The derivative 4d (R, R1 = H, R2 = OCH3,
R3 = OH) was equipotent to Ampicillin against B. subtilis
and had four times the activity against P. aeruginosa,
whereas oxidation to 5d reduced antimicrobial activity.
Furthermore, compound 4e (R = CH3, R1, R3 = H,
R2 = OCH3) was almost equipotent to Ampicillin against
Gram-negative bacteria, whereas its oxidation to the cor-
responding quinone 5e decreased the activity twice against
E. coli and increased it four times against P. aeruginosa.
Derivative 4f (R = CH3, R1, R3 = OCH3, R2 = H)
revealed almost half the activity against S. aureus and
E. coli, equal activity against B. subtilis and double the
activity against P. aeruginosa when compared with refer-
ence Ampicillin. Oxidation to quinone derivative 5f
maintained same activity against aforementioned Gram-
positive and Gram-negative organisms besides increasing
antifungal activity. Besides, compound 4g (R = CH3,
R1 = H, R2 = OH, R3 = OCH3) showed moderate activ-
ity against S. aureus and equal activity to Ampicillin
against P. aeruginosa, whereas its oxidation to 5g dimin-
ished activity against P. aeruginosa and maintained it
against S. aureus. The thiazoline 4h (R = CH3, R1 = H,
R2 = OCH3, R3 = OH) had about half the activity of
references against B. subtilis, E. coli, and C. albicans. It
also elicited twice the activity of Ampicillin against
P. aeruginosa. Converting to quinone 5h reduced the
antimicrobial activity against P. aeruginosa to be similar to
that of Ampicillin, whereas it diminished activity against
all other organisms. In addition, compounds 4i, 4j (R = Cl,
R1 = H, OCH3, R2 = OCH3, H, R3 = H, OCH3) revealed
about half the antimicrobial activity of Ampicillin against
E. coli as well as equal activity against P. aeruginosa,
whereas their oxidized forms 5i, 5j did not show any
antimicrobial activity except moderate activity for com-
pound 5j against S. aureus. Compound 4k (R = Cl,
R1 = H, R2 = OH, R3 = OCH3) did not exhibit any
The correlation between the activity of Ampicillin as
well as Clotrimazole and the most potent investigated
compounds against different tested organisms is illustrated
in the following figure:
400
350
300
250
200
150
100
50
Ampicillin
Clotrimazole
0
S. aureus
B. subtilis
E. coli
P. aeruginosa
C. albicans
Conclusion
The objective of this study was to synthesize and investi-
gate the antimicrobial activity of novel 2,5-dihydroxy-
phenyl-1,3-thiazoles and 1,4-benzoquinon-2-yl-1,3-thiazoles.
These compounds were subjected to in vitro antibacterial
and antifungal screening. The obtained data revealed that
ten compounds, namely 4b–4h and 5e, 5f, and 5l, exhibited
promising antimicrobial activity against tested organisms.
It is to be noted down that, among the tested hydroqui-
nones, compound 4b bearing two methoxy groups was
found to be the most potent member. It showed a broad
spectrum of antimicrobial activity with special high
activity against B. subtilis, E. coli, and P. aeruginosa. On
the other hand, compound 5f comprising two methoxy
groups was found to be the most potent member among the
benzoquinone series. Further investigation of such com-
pounds represents a fruitful matrix for the development of
more potent antimicrobial agents (Table 1).
Statistical analysis
As illustrated in Tables 2, 3, and 4, standard deviation
value was expressed in terms of SD. On the basis of
calculated value by Mann–Whitney test, it was observed
that differences less than 0.05 level were considered as
statistically significant.
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Med Chem Res (2013) 22:841–851
Experimental
Chemistry
apparatus and are all uncorrected. Infrared spectra (IR)
were recorded using KBr disks using a Perkin-Elmer 1430
1
Infrared spectrophotometer. H-NMR spectra were recor-
ded using a Jeol-NMR 500 MHZ spectrophotometer, in the
Faculty of Science, Alexandria University, and are reported
as d values (ppm) relative to tetramethylsilane as an
internal reference. 13C-NMR spectra were recorded using
JNM-LA 400 FT NMR system (400 MHz), Faculty of
Science, Assiut University. The type of signal was indi-
cated by one of the following letters: s = singlet,
d = doublet, t = triplet, q = quartet, and m = multiplet.
Mass spectra were run on a Finnigan mass spectrometer
model SSQ/7000 (70 eV) or on a gas chromatograph/mass
spectrometer Shimadzu GCMS-Qp2010 Plus (70 eV), in
the Faculty of Science, Cairo University. Elemental
microanalyses were performed at the microanalytical unit,
Faculty of Science, Cairo University or at Inspectorate
International Ltd., Jubail technical centre, Jubail labora-
tory, Saudi Arabia. Reactions’ progress was monitored by
thin-layer chromatography on silica gel (60 GF254, Merck)
using glass plates, and the spots were visualized by expo-
sure to iodine vapor or to UV-lamp at k 254 nm for few
seconds.
Melting points of synthesized compounds were determined
in open glass capillaries using a Griffin melting point
Table 1 The inhibition zones (IZ) in mm diameter
Comp. Gram-positive bacteria Gram-negative bacteria Fungi
no.
S. aureus B. subtilis E. coli P. aeruginosa C. albicans
4a
4b
4c
4d
4e
4f
14
16
15
16
15
14
15
16
15
13
16
14
15
14
15
14
16
16
14
15
14
14
16
13
15
15
16
15
13
17
15
14
14
15
16
14
15
15
15
15
14
15
15
14
15
14
14
14
14
18
14
24
15
17
14
14
14
18
15
13
16
14
15
14
16
14
15
14
16
13
16
14
14
16
15
12
16
14
16
13
12
16
14
14
15
14
14
16
15
14
15
14
16
16
15
14
12
14
15
14
15
14
12
14
15
13
14
12
15
15
12
14
14
13
15
15
14
14
15
15
4g
4h
4i
4j
4k
4l
5a
5b
5c
5d
5e
5f
General method for the preparation of 4-aryl-
1-substituted benzylidene thiosemicarbazides (3a–l)
A solution of the selected 4-aryl thiosemicarbazide
2a–c (5 mmol) in 99.9 % ethanol (20 ml) was gradually
added with stirring to a well-stirred solution of an equi-
molar amount of the selected aldehyde 1a–d (5 mmol) in
99.9 % ethanol (4 ml). The reaction mixture was stirred for
an additional hour and set aside at room temperature for an
overnight whereupon the products separated out. The
obtained products were filtered, washed with cold ethanol,
air dried, and crystallized from ethanol.
5g
5h
5i
5j
5k
5l
Table 2 Inhibition zones (IZ) in mm diameter
Organism
Inhibition zone (mm)
Compounds 4a–l
Min–Max
Significance (P)
Compounds 5a–l
Mean SD
Min–Max
Mean SD
Gram-positive bacteria
S. aureus
13–16
13–17
14.9 0.9
14.9 1.0
13–16
14–15
14.7 0.9
14.6 0.5
Z = 0.664 (0.507)
Z = 0.883 (0.377)
B. subtilis
Gram-negative bacteria
E. coli
13–24
12–16
15.8 3.1
14.3 1.5
13–16
14–16
14.8 1.1
14.8 0.8
Z = 0.482 (0.63)
Z = 0.785 (0.432)
P. aeruginosa
Fungi
C. albicans
12–15
13.7 1.2
12–15
14.3 0.9
Z = 1.346 (0.178)
SD standard deviation, Z Mann–Whitney test
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Med Chem Res (2013) 22:841–851
845
Table 3 Minimal inhibitory concentrations (MIC) in lg/ml
Organism
MIC (lg/ml)
Compounds 4a–l
Min–Max
Significance (P)
Compounds 5a–l
Mean SD
Min–Max
Mean SD
Gram-positive bacteria
S. aureus
12.5–100
12.5–50
45.8 29.4
38.5 17.2
12.5–100
12.5–100
53.1 31.1
65.6 32.5
Z = 0.608 (0.543)
Z = 1.093 (0.036)*
B. subtilis
Gram-negative bacteria
E. coli
12.5–100
12.5–100
40.6 31.1
47.9 28.6
25–100
58.3 32.6
65.6 32.5
Z = 1.563 (0.118)
Z = 1.357 (0.175)
P. aeruginosa
Fungi
12.5–100
C. albicans
12.5–100
52.1 32.3
12.5–100
51.0 26.4
Z = 0.093 (0.926)
SD standard deviation, Z Mann–Whitney test
* Significant at P B 0.05
Table 4 Minimal germicidal concentrations (MBC/MFC) in lg/ml
Organism
MBC/MFC (lg/ml)
Compounds 4a–l
Significance (P)
Compounds 5a–l
Min–Max
Mean SD
Min–Max
Mean SD
Gram-positive bacteria
S. aureus
25–100
25–100
58.3 26.8
47.9 19.8
25–100
25–100
60.4 24.9
72.9 29.1
Z = 0.302 (0.763)
Z = 2.145 (0.032)*
B. subtilis
Gram-negative bacteria
E. coli
25–100
25–100
56.3 28.5
58.3 26.8
50–100
25–100
66.7 24.6
72.9 29.1
Z = 1.18 (0.238)
Z = 1.242 (0.214)
P. aeruginosa
Fungi
C. albicans
25–100
62.5 29.2
25–100
64.6 27.1
Z = 0.258 (0.797)
SD standard deviation, Z Mann–Whitney test
* Significant at P B 0.05
1-(3-Hydroxy-4-methoxybenzylidene)-
1-(4-Methoxybenzylidene)-
4-(4-tolyl)thiosemicarbazide 3h
4-(4-chlorophenyl)thiosemicarbazide 3i
Yield 91 %. M.p. 184–186 °C. IR (KBr, t cm-1): 3517
(OH), 3308, 3151 (tNH), 1610 (C=N), 1543 (dNH), 1543,
1272, 1128, 981 (N–C=S thioamide I, II, III, IV bands),
1201, 1072 (C–O–C). 1H-NMR (CD3COCD3, d ppm):
2.36 (s, 3H, C6H4–CH3); 3.92 (s, 3H, OCH3); 6.85 (d, 1H,
J: 8.4 Hz, 3-hydroxy-4-methoxyphenyl-C5-H); 7.09 (dd,
1H, J: 8.4, 1.55 Hz, 3-hydroxy-4-methoxyphenyl-C6-H);
7.20 (d, 2H, J: 8.4 Hz, p-tolyl-C3,5-H); 7.37 (d, 1H,
J: 1.55 Hz, 3-hydroxy-4-methoxyphenyl-C2-H); 7.44 (d,
2H, J: 8.4 Hz, p-tolyl-C2,6-H); 7.92 (s, 1H, CH=N);
9.12, 9.84, 10.60 (three s, each 1H, 2NH and OH,
D2O-exch.). Anal. calcd. (%) for C16H17N3O2S: C 60.93,
Yield 87 %. M.p. 190–192 °C. IR (KBr, t cm-1): 3323,
3150 (tNH), 1605 (C=N), 1543 (dNH), 1543, 1273, 1168,
942 (N–C=S thioamide I, II, III, IV bands), 1247, 1076
(C–O–C). Anal. calcd. (%) for C15H14ClN3OS: C 56.33,
H 4.41, N 13.14. Found: C 56.52, H 4.60, N 13.28.
1-(2,5-Dimethoxybenzylidene)-
4-(4-chlorophenyl)thiosemicarbazide 3j
Yield 88 %. M.p. 188–190 °C. IR (KBr, t cm-1): 3279,
3111 (tNH), 1589 (C=N), 1543 (dNH), 1543, 1263, 1134,
962 (N–C=S thioamide I, II, III, IV bands), 1215, 1044
(C–O–C). Anal. calcd. (%) for C16H16ClN3O2S: C 54.93,
H 4.61, N 12.01. Found: C 54.57, H 4.20, N 11.48.
H
5.43,
N 13.32. Found: C 60.97, H 5.80, N
13.41.
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Med Chem Res (2013) 22:841–851
1-(3-Hydroxy-4-methoxybenzylidene)-
(OH), 1584 (C=N), 1265, 1121 (C–S–C), 1206, 1025
(C–O–C). Anal. calcd. (%) for C23H19N3O4S: C 63.73, H
4.42, N 9.69. Found: C 63.82, H 4.50, N 9.53.
4-(4-chlorophenyl)thiosemicarbazide 3l
Yield 99 %. M.p. 196–198 °C. IR (KBr, t cm-1): 3435
(OH), 3316, 3180 (tNH), 1603 (C=N), 1537 (dNH), 1581,
1276, 1154, 984 (N–C=S thioamide I, II, III, IV bands), 1247,
1051 (C–O–C). Anal. calcd. (%) for C15H14ClN3O2S:
C 53.65, H 4.20, N 12.51. Found: C 53.66, H 5.02, N 12.80.
N1-benzylidene-N2-[3-(3-hydroxy-4-methoxyphenyl)-
4-(2,5-dihydroxyphenyl)-1,3-thiazol-2-
ylidene]hydrazine 4d
Crystallized from ethanol. Yield 99 %. M.p. 162–164 °C.
IR (KBr, t cm-1): 3415 (OH), 1588 (C=N), 1266, 1178
(C–S–C), 1213, 1033 (C–O–C). Anal. calcd. (%) for
C23H19N3O4S: C 63.73, H 4.42, N 9.69. Found: C 63.03, H
4.00, N 9.55.
N1-substituted benzylidene-N2-[3-aryl-4-(2,
5-dihydroxyphenyl)-1,3-thiazol-2-ylidene]hydrazines
(4a–l)
A solution of 2,5-dihydroxyphenacyl bromide (1.39 g,
6 mmol) in 99.9 % ethanol (20 ml) was gradually added to
a suspension of the aryl thiosemicarbazones 3a–l (6 mmol)
in 99.9 % ethanol (20 ml) containing anhydrous sodium
acetate (0.49 g, 6 mmol). The reaction mixture was heated
under reflux for 18 h, concentrated, cooled, poured onto
crushed ice while stirring, and set aside for an overnight.
The formed precipitates were filtered, washed several times
with water, air dried, and crystallized.
N1-4-methylbenzylidene-N2-[3-(4-methoxyphenyl)-
4-(2,5-dihydroxyphenyl)-1,3-thiazol-2-ylidene]
hydrazine 4e
Crystallized from benzene. Yield 93 %. M.p. 172–174 °C.
IR (KBr, t cm-1): 3300 (OH), 1606 (C=N), 1244, 1168
(C–S–C), 1196, 1026 (C–O–C). Anal. calcd. (%) for
C24H21N3O3S: C 66.80, H 4.91, N 9.74. Found: C 66.75, H
4.99, N 9.60.
N1-benzylidene-N2-[3-(4-methoxyphenyl)-4-(2,
5-dihydroxyphenyl)-1,3-thiazol-2-ylidene]hydrazine 4a
N1-4-methylbenzylidene-N2-[3-(2,5-dimethoxyphenyl)-
4-(2,5-dihydroxyphenyl)-1,3-thiazol-2-ylidene]
hydrazine 4f
Crystallized from ethyl acetate. Yield 88 %. M.p.
212–214 °C. IR (KBr, t cm-1): 3288 (OH), 1603 (C=N),
1251, 1166 (C–S–C), 1219, 1029 (C–O–C). 1H-NMR
(DMSO-d6, dppm): 3.74 (s, 3H, OCH3); 6.33 (s, 1H, thiaz-
oline-C5-H); 6.41–6.49 (m, 3H, dihydroxyphenyl-C3,4,6-H);
6.94 (d, 2H, J: 8.4 Hz, methoxyphenyl-C3,5-H); 7.16–7.28
(m, 5H, phenyl-H); 7.58 (d, 2H, J: 8.4 Hz, methoxyphenyl-
C2,6-H); 8.04 (s, 1H, CH=N); 8.77, 8.87 (two s, each 1H,
OH, D2O-exch.). Anal. calcd. (%) for C23H19N3O3S: C
66.17, H 4.59, N 10.07. Found: C 66.48, H 4.64, N 10.17.
Crystallized from benzene. Yield 94 %. M.p. 172–174 °C.
IR (KBr, t cm-1): 3415 (OH), 1588 (C=N), 1266, 1178
(C–S–C), 1213, 1033 (C–O–C). 1H-NMR (DMSO-d6,
d ppm): 2.22 (s, 3H, C6H4–CH3); 3.70, 3.71 (two s, each
3H, OCH3); 6.33 (s, 1H, thiazoline-C5-H); 6.43–6.50 (m,
3H, dihydroxyphenyl-C3,4,6-H); 6.91 (dd, 1H, J: 9.2,
3.05 Hz, dimethoxyphenyl-C4-H); 6.95 (d, 1H, J: 9.2 Hz,
dimethoxyphenyl-C3-H); 7.04–7.10 (m, 4H, p-tolyl-H);
7.33 (d, 1H, J: 3.05 Hz, dimethoxyphenyl-C6-H); 8.23 (s,
1H, CH=N); 8.77, 8.87 (two s, each 1H, OH, D2O-exch.).
Anal. calcd. (%) for C25H23N3O4S: C 65.06, H 5.02, N
9.10. Found: C 64.90, H 5.10, N 9.10.
N1-benzylidene-N2-[3-(2,5-dimethoxyphenyl)-4-(2,
5-dihydroxyphenyl)-1,3-thiazol-2-ylidene]hydrazine 4b
Crystallized from ethyl acetate. Yield 97 %. M.p.
220–222 °C (with decomposition). IR (KBr, t cm-1): 3280
(OH), 1598 (C=N), 1271, 1160 (C–S–C), 1215, 1033 (C–
O–C). Anal. calcd. (%) for C24H21N3O4S: C 64.41, H 4.73,
N 9.39. Found: C 64.98, H 4.40, N 9.52.
N1-4-methylbenzylidene-N2-[3-(4-hydroxy-
3-methoxyphenyl)-4-(2,5-dihydroxyphenyl)-1,
3-thiazol-2-ylidene]hydrazine 4g
N1-benzylidene-N2-[3-(4-hydroxy-3-methoxyphenyl)-
4-(2,5-dihydroxyphenyl)-1,3-thiazol-2-ylidene]
hydrazine 4c
Crystallized from ethyl acetate. Yield 92 %. M.p.
240–242 °C. IR (KBr, t cm-1): 3371(OH), 1594 (C=N),
1272, 1116 (C–S–C), 1204, 1031 (C–O–C). Anal. calcd.
(%) for C24H21N3O4S: C 64.41, H 4.73, N 9.39. Found: C
64.77, H 4.46, N 9.35.
Crystallized from methylene chloride. Yield 96 %. M.p.
150–152 °C (with decomposition). IR (KBr, t cm-1): 3376
123

Med Chem Res (2013) 22:841–851
847
N1-4-methylbenzylidene-N2-[3-(3-hydroxy-
4-methoxyphenyl)-4-(2,5-dihydroxyphenyl)-1,
3-thiazol-2-ylidene]hydrazine 4h
1273, 1120 (C–S–C), 1203, 1027 (C–O–C). 1H-NMR
(CD3COCD3, d ppm): 3.86 (s, 3H, OCH3); 6.26 (s, 1H,
thiazoline-C5-H); 6.54 (d, 1H, J: 8.4 Hz, dihydroxyphenyl-
C3-H); 6.61 (dd, 1H, J: 8.4, 3.05 Hz, dihydroxyphenyl-C4-
H); 6.67 (d, 1H, J: 3.05 Hz, dihydroxyphenyl-C6-H); 6.82
(d, 1H, J: 8.4 Hz, 4-hydroxy-3-methoxyphenyl-C5-H);
7.12 (dd, 1H, J: 8.4, 1.55 Hz, 4-hydroxy-3-methoxy-
phenyl-C6-H); 7.26–7.31 (m, 4H, p-chlorophenyl-H); 7.37
(d, 1H, J: 1.55 Hz, 4-hydroxy-3-methoxyphenyl-C2-H);
8.00 (s, 1H, CH=N); 8.02, 8.04 (two s, each 1H, OH,
D2O-exch.). Anal. calcd. (%) for C23H18ClN3O4S: C
59.04, H 3.88, N 8.98. Found: C 59.00, H 3.80, N 9.20. EI
MS, m/z (%): 469 (31) (M?Á?2), 467 (56) (M?Á), 209
(100).
Crystallized from benzene. Yield 92 %. M.p. 240–242 °C.
IR (KBr, t cm-1): 3290 (OH), 1606 (C=N), 1269, 1121 (C–
S–C), 1205, 1022 (C–O–C). 1H-NMR (CD3COCD3, d ppm):
2.22 (s, 3H, C6H4–CH3); 3.74 (s, 3H, OCH3); 6.29 (s, 1H,
thiazoline-C5-H); 6.40–6.50 (m, 3H, dihydroxyphenyl-
C3,4,6-H); 6.88 (d, 1H, J: 8.4 Hz, 3-hydroxy-4-methoxy-
phenyl-C5-H); 7.02–7.08 (m, 4H, p-tolyl-H); 7.19 (dd, 1H, J:
8.4, 1.55 Hz, 3-hydroxy-4-methoxyphenyl-C6-H); 7.33 (d,
1H, J: 1.55 Hz, 3-hydroxy-4-methoxyphenyl-C2-H); 7.92 (s,
1H, CH=N); 8.76, 8.86, 9.17 (three s, each 1H, OH, D2O-
exch.). Anal. calcd. (%) for C24H21N3O4S: C 64.41, H 4.73,
N 9.39. Found: C 64.82, H 5.10, N 9.39.
N1-4-chlorobenzylidene-N2-[3-(3-hydroxy-
4-methoxyphenyl)-4-(2,5-dihydroxyphenyl)-1,
3-thiazol-2-ylidene]hydrazine 4l
N1-4-chlorobenzylidene-N2-[3-(4-methoxyphenyl)-
4-(2,5-dihydroxyphenyl)-1,3-thiazol-2-ylidene]
hydrazine 4i
Crystallized from methylene chloride. Yield 86 %. M.p.
162–164 °C. IR (KBr, t cm-1): 3267 (OH), 1605 (C=N),
1272, 1121 (C–S–C), 1211, 1020 (C–O–C). 1H-NMR
(CD3COCD3, d ppm): 3.83 (s, 3H, OCH3); 6.27 (s, 1H,
thiazoline-C5-H); 6.53 (d, 1H, J: 8.4 Hz, dihydroxyphenyl-
C3-H); 6.61 (dd, 1H, J: 8.4, 3.05 Hz, dihydroxyphenyl-C4-
H); 6.67 (d, 1H, J: 3.05 Hz, dihydroxyphenyl-C6-H); 6.93
(d, 1H, J: 8.4 Hz, 3-hydroxy-4-methoxyphenyl-C5-H);
7.06 (dd, 1H, J: 8.4, 2.3 Hz, 3-hydroxy-4-methoxyphenyl-
C6-H); 7.26-7.30 (m, 4H, p-chlorophenyl-H); 7.32 (d, 1H,
J: 2.3 Hz, 3-hydroxy-4-methoxyphenyl-C2-H); 7.84, 8.02
(two s, each 1H, OH, D2O-exch.); 7.79 (s, 1H, CH = N).
13C-NMR (DMSO-d6, d ppm): 55.6, 101, 111.8, 112.3,
116.1, 117.3, 118.1, 120.1, 128.1, 128.2, 128.8, 130, 131.6,
136.4, 137.1, 146.6, 147.6, 149.3, 149.4, 151.4, 168.2.
Anal. calcd. (%) for C23H18ClN3O4S: C 59.04, H 3.88, N
8.98. Found: C 58.99, H 3.80, N 8.90. EI MS, m/z (%): 469
(14.7) (M?Á?2), 467 (52.3) (M?Á), 209 (100).
Crystallized from ethyl acetate. Yield 99 %. M.p.
228–230 °C. (with decomposition). IR (KBr, t cm-1):
3286 (OH), 1604 (C=N), 1251, 1166 (C–S–C), 1219, 1024
(C–O–C). Anal. calcd. (%) for C23H18ClN3O3S: C 61.13, H
4.01, N 9.30. Found: C 61.80, H 3.91, N 9.43. EI MS, m/
z (%): 453 (30.6) (M?Á?2), 451 (76.4) (M?Á), 120 (100).
N1-4-chlorobenzylidene-N2-[3-(2,5-dimethoxyphenyl)-
4-(2,5-dihydroxyphenyl)-1,3-thiazol-
2-ylidene]hydrazine 4j
Crystallized from ethanol/water 9:1. Yield 85 %. M.p.
174–176 °C. IR (KBr, t cm-1): 3271 (OH), 1597 (C=N),
1269, 1160 (C–S–C), 1215, 1026 (C–O–C). 1H-NMR
(CD3COCD3, d ppm): 3.76, 3.77 (two s, each 3H, OCH3);
6.30 (s, 1H, thiazoline-C5-H); 6.54 (d, 1H, J: 9.2 Hz,
dihydroxyphenyl-C3-H); 6.62 (dd, 1H, J: 9.2, 3.05 Hz,
dihydroxyphenyl-C4-H); 6.68 (d, 1H, J: 3.05 Hz, dihy-
droxyphenyl-C6-H); 6.90 (dd, 1H, J: 9.2, 3.05 Hz, dime-
thoxyphenyl-C4-H); 6.93 (d, 1H, J: 9.2 Hz, dimethoxy-
phenyl-C3-H); 7.27–7.33 (m, 4H, p-chlorophenyl-H); 7.52
(d, 1H, J: 3.05 Hz, dimethoxyphenyl-C6-H); 8.03, 8.04 (two
s, each 1H, OH, D2O-exch.); 8.40 (s, 1H, CH=N). Anal.
calcd. (%) for C24H20ClN3O4SÁ‘H2O: C 58.71, H 4.31, N
8.56. Found: C 58.89, H 3.82, N 8.56.
N1-substituted benzylidene-N2-[3-aryl-4-(1,
4-benzoquinon-2-yl)-1,3-thiazol-2-ylidene]hydrazines
(5a–l)
A cold solution of the appropriate hydroquinone 4a–l
(1 mmol) in DMF (5 ml) was gradually treated with cold
20 % ferric chloride in water/DMF 1:1 (15 ml). Stirring
was continued for 30 min and then the reaction mixture
was diluted with water (30 ml) whereupon blue or green
precipitates were formed. The formed colored precipitates
were filtered, washed with water several times till free from
ferric ions, air dried, and crystallized from the proper sol-
vent as blue or green crystals.
N1-4-chlorobenzylidene-N2-[3-(4-hydroxy-
3-methoxyphenyl)-4-(2,5-dihydroxyphenyl)-1,
3-thiazol-2-ylidene]hydrazine 4k
Crystallized from methylene chloride. Yield 86 %. M.p.
186–188 °C. IR (KBr, t cm-1): 3384 (OH), 1596 (C=N),
123

848
Med Chem Res (2013) 22:841–851
N1-benzylidene-N2-[3-(4-methoxyphenyl)-4-(1,4-
benzoquinon-2-yl)-1,3-thiazol-2-ylidene]hydrazine 5a
1604 (C=N), 1296, 1164 (C–S–C), 1248, 1028 (C–O–C).
1H-NMR (CHCl3, d ppm): 2.34 (s, 3H, C6H4–CH3); 3.82
(s, 3H, OCH3); 6.65 (s, 1H, thiazoline-C5-H); 6.44 (d, 1H,
J: 2.3 Hz, benzoquinonyl-C6-H); 6.62-6.69 (m, 2H,
benzoquinonyl-C3,4-H); 6.88 (d, 2H, J: 8.4 Hz, methoxy-
phenyl-C3,5-H); 7.17 (d, 2H, J: 8.4 Hz, p-tolyl-C3,5-H);
7.20 (d, 2H, J: 8.4 Hz, p-tolyl-C2,6-H); 7.63 (d, 2H, J:
8.4 Hz, methoxyphenyl-C2,6-H); 8.18 (s, 1H, CH=N).
Anal. calcd. (%) for C24H19N3O3S: C 67.12, H 4.46, N
9.78. Found: C 66.85, H 4.32, N 9.54.
Crystallized from n-hexane. Yield 74 %. M.p. 110–112 °C.
IR (KBr, t cm-1): 1649 (C=O), 1608 (C=N), 1296, 1159
(C–S–C), 1215, 1072 (C–O–C). Anal. calcd. (%) for
C23H17N3O3S: C 66.49, H 4.12, N 10.11. Found: C 66.50,
H 4.21, N 10.14.
N1-benzylidene-N2-[3-(2,5-dimethoxyphenyl)-4-(1,4-
benzoquinon-2-yl)-1,3-thiazol-2-ylidene]hydrazine 5b
N1-4-methylbenzylidene-N2-[3-(2,5-dimethoxyphenyl)-
4-(1,4-benzoquinon-2-yl)-1,3-thiazol-2-
ylidene]hydrazine 5f
Crystallized from methanol. Yield 80 %. M.p. 164–166 °C
(with decomposition). IR (KBr, t cm-1): 1658 (C=O),
1597 (C=N), 1278, 1160 (C–S–C), 1215, 1041 (C–O–C).
1H-NMR (CH3COCH3, d ppm): 3.71 (s, 3H, OCH3); 6.69
(s, 1H, thiazoline-C5-H); 6.67 (d, 1H, J: 2.3 Hz, benzoqu-
inonyl-C6-H); 6.77 (d, 1H, J: 8.4 Hz, benzoquinonyl-C3-H);
6.90–6.98 (m, 3H, benzoquinonyl-C4-H and dimethoxy-
phenyl-C3,4-H); 7.27–7.35 (m, 3H, dimethoxyphenyl-C6-H
and phenyl-C2,6-H); 7.36–7.42 (m, 3H, phenyl-C3,4,5-H);
8.29 (s, 1H, CH=N). Anal. calcd. (%) for C24H19N3O4S: C
64.71, H 4.30, N 9.43. Found: C 64.91, H 4.22, N 9.22.
Crystallized from methanol. Yield 95 %. M.p.
188–190 °C (with decomposition). IR (KBr, t cm-1):
1654 (C=O), 1598 (C=N), 1262, 1163 (C–S–C), 1217,
1042 (C–O–C). 1H-NMR (CHCl3, d ppm): 2.35 (s, 3H,
C6H4–CH3); 3.75, 3.82 (two s, each 3H, OCH3); 6.46 (d,
1H, J: 2.3 Hz, benzoquinonyl-C6-H); 6.62 (s, 1H, thiaz-
oline-C5-H); 6.63-6.69 (m, 2H, benzoquinonyl-C3,4-H);
6.80 (d, 1H, J: 9.2 Hz, dimethoxyphenyl-C3-H); 6.87 (dd,
1H, J: 9.2, 3.05 Hz, dimethoxyphenyl-C4-H); 7.18 (d, 2H,
J: 8.4 Hz, p-tolyl-C3,5-H); 7.21 (d, 2H, J: 8.4 Hz, p-tolyl-
C2,6-H); 7.56 (d, 1H, J: 3.05 Hz, dimethoxyphenyl-C6-H);
8.64 (s, 1H, CH=N). Anal. calcd. (%) for C25H21N3O4SÁ‘
H2O: C 64.09, H 4.73, N 8.97. Found: C 64.22, H 4.48, N
9.54.
N1-benzylidene-N2-[3-(4-hydroxy-3-methoxyphenyl)-
4-(1,4-benzoquinon-2-yl)-1,3-thiazol-2-
ylidene]hydrazine 5c
Crystallized from benzene. Yield 85 %. M.p. 200 °C (with
decomposition). IR (KBr, t cm-1): 3309 (OH), 1652
(C=O), 1607 (C=N), 1276, 1167 (C–S–C), 1243, 1051 (C–
O–C). Anal. calcd. (%) for C23H17N3O4S: C 64.03, H 3.97,
N 9.74. Found: C 63.75, H 4.77, N 9.58.
N1-4-methylbenzylidene-N2-[3-(4-hydroxy-
3-methoxyphenyl)-4-(1,4-benzoquinon-2-yl)-1,
3-thiazol-2-ylidene]hydrazine 5g
N1-benzylidene-N2-[3-(3-hydroxy-4-methoxyphenyl)-
4-(1,4-benzoquinon-2-yl)-1,3-thiazol-2-
ylidene]hydrazine 5d
Crystallized from benzene. Yield 90 %. M.p. 88–90 °C
(with decomposition). IR (KBr, t cm-1): 3409 (OH), 1657
(C=O), 1589 (C=N), 1280, 1159 (C–S–C), 1230, 1058 (C–
O–C). Anal. calcd. (%) for C24H19N3O4S: C 64.71, H 4.30,
N 9.43. Found: C 64.70, H 4.38, N 8.90.
Crystallized from benzene. Yield 95 %. M.p. 180–182 °C
(with decomposition). IR (KBr, t cm-1): 3397 (OH), 1652
(C=O), 1596 (C=N), 1286, 1161 (C–S–C), 1231, 1072 (C–
O–C). Anal. calcd. (%) for C23H17N3O4S: C 64.03, H 3.97,
N 9.74. Found: C 64.06, H 3.62, N 9.21.
N1-4-methylbenzylidene-N2-[3-(3-hydroxy-
4-methoxyphenyl)-4-(1,4-benzoquinon-2-yl)-1,3-
thiazol-2-ylidene]hydrazine 5h
N1-4-methylbenzylidene-N2-[3-(4-methoxyphenyl)-
4-(1,4-benzoquinon-2-yl)-1,3-thiazol-2-
ylidene]hydrazine 5e
Crystallized from methanol. Yield 84 %. M.p. 200–202 °C
(with decomposition). IR (KBr, t cm-1): 3225 (OH), 1661
(C=O), 1606 (C=N), 1278, 1175 (C–S–C), 1246, 1071 (C–
O–C). Anal. calcd. (%) for C24H19N3O4S: C 64.71, H 4.30,
N 9.43. Found: C 64.50, H 4.20, N 9.15.
Crystallized from ethanol. Yield 84 %. M.p. 178–180 °C
(with decomposition). IR (KBr, t cm-1): 1665 (C=O),
123

Med Chem Res (2013) 22:841–851
849
N1-4-chlorobenzylidene-N2-[3-(4-methoxyphenyl)-
4-(1,4-benzoquinon-2-yl)-1,3-thiazol-2-
ylidene]hydrazine 5i
N1-4-chlorobenzylidene-N2-[3-(2,5-dimethoxyphenyl)-
4-(1,4-benzoquinon-2-yl)-1,3-thiazol-2-
ylidene]hydrazine 5j
Crystallized from ethanol. Yield 98 %. M.p. 188–190 °C (with
decomposition). IR (KBr, t cm-1): 1652 (C=O), 1608 (C=N),
1285, 1168 (C–S–C), 1244, 1030 (C–O–C). 1H-NMR (CHCl3,
d ppm): 3.83 (s, 3H, OCH3); 6.54 (d, 1H, J: 2.3 Hz, benzoqui-
nonyl-C6-H); 6.63 (s, 1H, thiazoline-C5-H); 6.63-6.73 (m, 2H,
benzoquinonyl-C3,4-H); 6.89 (d, 2H, J: 8.4 Hz, methoxyphenyl-
C3,5-H); 7.26 (d, 2H, J: 8.4 Hz, p-chlorophenyl-C2,6-H); 7.38 (d,
2H, J: 8.4 Hz, p-chlorophenyl-C3,5-H); 7.64 (d, 2H, J: 8.4 Hz,
methoxyphenyl-C2,6-H); 8.22 (s, 1H, CH=N). 13C-NMR
(DMSO-d6,d ppm): 55.3, 111.6, 114, 127.8, 129.1, 129.5, 129.6,
132.3, 132.6, 134, 135.9, 136.4, 136.5, 136.6, 153.76, 161.11,
167.76, 184.07, 186.40. Anal. calcd. (%) for C23H16ClN3O3SÁ‘
H2O: C 60.20, H 3.73, N 9.16. Found: C 60.24, H 3.56, N 9.05. EI
MS, m/z (%): 449 (79.5) (M?Á), 118 (100).
Crystallized from methanol. Yield 85 %. M.p. 170–172 °C
(with decomposition). IR (KBr, t cm-1): 1651 (C=O),
1580 (C=N), 1283, 1164 (C–S–C), 1260, 1041 (C–O–C).
Anal. calcd. (%) for C24H18ClN3O4S: C 60.06, H 3.78, N
8.76. Found: C 59.80, H 3.85, N 8.90.
N1-4-chlorobenzylidene-N2-[3-(4-hydroxy-3-
methoxyphenyl)-4-(1,4-benzoquinon-2-yl)-1,3-thiazol-
2-ylidene]hydrazine 5k
Crystallized from benzene. Yield 97 %. M.p. 164 °C (with
decomposition). IR (KBr, t cm-1): 3455 (OH), 1649
(C=O), 1596 (C=N), 1268, 1198 (C–S–C), 1250, 1034
Table 5 Minimal inhibitory concentrations (MIC) and minimal germicidal concentrations (MBC/MFC) of tested compounds in lg/ml
Comp. no.
Gram-positive bacteria
Gram-negative bacteria
Fungi
S. aureus
B. subtilis
E. coli
P. aeruginosa
C. albicans
MIC
MIC
MBC
MIC
MBC
MIC
MBC
MIC
MBC
MFC
4a
4b
4c
4d
4e
4f
50
50
50
25
100
50
25
50
50
100
100
50
50
50
50
50
50
50
25
50
100
100
50
100
50
–
50
50
25
50
50
25
50
50
25
50
50
50
50
12.5
50
12.5
12.5
50
12.5
50
25
12.5
100
50
50
25
50
12.5
100
100
50
25
12.5
50
25
50
12.5
50
25
100
100
50
50
12.5
25
25
50
12.5
25
12.5
50
25
50
25
50
4g
4h
4i
50
50
100
50
50
100
50
50
50
25
25
50
25
25
12.5
50
25
100
50
50
50
25
50
50
50
50
4j
50
50
25
50
50
50
50
100
100
50
4k
4l
50
50
50
100
100
25
100
100
50
100
100
50
100
100
50
100
25
25
50
100
50
5a
5b
5c
5d
5e
5f
50
50
50
50
50
50
50
50
50
50
50
50
50
25
50
100
100
50
100
50
100
50
100
100
12.5
25
100
100
25
25
50
50
100
50
100
50
100
50
50
25
50
12.5
25
12.5
100
50
25
25
50
50
25
50
5g
5h
5i
100
50
50
50
100
50
100
50
50
50
100
100
25
50
50
50
100
100
100
50
100
100
100
25
100
100
100
50
100
100
100
25
100
100
100
50
100
100
50
100
100
100
50
100
50
5j
5k
5l
100
50
50
50
12.5
–
25
A*
C**
5
12.5
–
–
10
–
50
–
–
–
–
–
–
–
–
–
5
–
* A Ampicillin trihydrate (Standard broad spectrum antibiotic)
** C Clotrimazole (Standard broad spectrum antifungal agent)
123

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Med Chem Res (2013) 22:841–851
Minimal germicidal concentration (MBC or MFC)
(C–O–C). Anal. calcd. (%) for C23H16ClN3O4S: C 59.29, H
3.46, N 9.02. Found: C 59.74, H 3.20, N 8.66.
measurement
MIC tests were extended to measure the MBC or MFC as
follows: A loopfull from the tube not showing visible
growth (MIC) was spread over a quarter of Mu¨ller–Hinton
agar plate. After incubation, 24 h for bacteria and 48 h for
fungi, the plates were examined for growth. Again, the tube
containing the lowest concentration of the test compound
that failed to yield growth on subculture plates was judged
to contain the MBC of that compound for the respective
test organism. The MBC/MFC values of the tested com-
pounds are listed in Table 5.
N1-4-chlorobenzylidene-N2-[3-(3-hydroxy-
4-methoxyphenyl)-4-(1,4-benzoquinon-2-yl)-1,
3-thiazol-2-ylidene]hydrazine 5l
Crystallized from methanol. Yield 91 %. M.p. 200 °C
(with decomposition). IR (KBr, t cm-1): 3238 (OH), 1659
(C=O), 1596 (C=N), 1277, 1168 (C–S–C), 1250, 1061
(C–O–C). Anal. calcd. (%) for C23H16ClN3O4SÁ‘H2O: C
58.17, H 3.61, N 8.85. Found: C 58.01, H 3.08, N 8.63.
Antimicrobial screening
References
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