Synthesis and chemistry of some new 2-mercaptoimidazole derivatives of possible antimicrobial activity

Article abstract of DOI:10.1080/10426500490262315

4,5-Diaryl-2,3-dihydro-2-mercaptoimidazoles (2a-e) were synthesized. They reacted with chloroacetic acid in gl. acetic acid / Ac₂O in presence of anhyd. sodium acetate afforded 5,6-diaryl-2,3-dihydroimidazo[2,1-b]thiazol-3- ones (3a-d). Also th

Full text of DOI:10.1080/10426500490262315

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Phosphorus, Sulfur, and Silicon and the Related
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SYNTHESIS AND CHEMISTRY OF SOME NEW 2-
MERCAPTOIMIDAZOLE DERIVATIVES OF POSSIBLE
ANTIMICROBIAL ACTIVITY
M. A. Salama a & L. A. Almotabacani b
a National Research Center, Dokki, Cairo, Egypt
b Girls College of Education, Riyadh, Saudi Arabia
Published online: 11 Aug 2010.
To cite this article: M. A. Salama & L. A. Almotabacani (2004) SYNTHESIS AND CHEMISTRY OF SOME NEW 2-
MERCAPTOIMIDAZOLE DERIVATIVES OF POSSIBLE ANTIMICROBIAL ACTIVITY, Phosphorus, Sulfur, and Silicon and the Related
Elements, 179:2, 305-319, DOI: 10.1080/10426500490262315
To link to this article: http://dx.doi.org/10.1080/10426500490262315
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Phosphorus, Sulfur, and Silicon, 179:305–319, 2004
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490262315
SYNTHESIS AND CHEMISTRY OF SOME NEW
2-MERCAPTOIMIDAZOLE DERIVATIVES OF
POSSIBLE ANTIMICROBIAL ACTIVITY
M. A. Salamaa and L. A. Almotabacanib
National Research Center, Dokki, Cairo, Egypt;a and
Girls College of Education, Riyadh, Saudi Arabiab
(Received April 21, 2003; accepted August 4, 2003)
4,5-Diaryl-2,3-dihydro-2-mercaptoimidazoles (2a–e) were synthe-
sized. They reacted with chloroacetic acid in gl. acetic acid/Ac2O in
presence of anhyd. sodium acetate afforded 5,6-diaryl-2,3-dihydro-
imidazo[2,1-b]thiazol-3-ones (3a–d). Also these compounds were
prepared by the action of chloroacetyl chloride on compounds (2)
in pyridine. Compounds (3a–d) on condensation with aromatic
aldehydes yield 2-arylmethylene-5,6-diaryl-2,3-dihydroimidazo[2,1-
b]-thiazol-3-ones (4a–q). The latter compounds were prepared directly
by the reaction of (2) with chloroacetic acid and the aromatic
aldehydes. Compounds (3a–d) coupled with aryldiazonium salts
in pyridine to give 2-arylhydrazono-5,6-diaryl-2,3-dihydroimidazo-
[2,1-b]thiazol-3-ones (5a–r). Also compounds (2) when reacted with
2 or 3-bromopropionic acid afford 2,3-di-hydro-5,6-diaryl-2-methy-
limidazo[2,1-b]thiazol-3-ones (6a–d) and 2,3-di-hydro-6,7-diaryl
imidazo-[2,1-b]-1,3-thiazin-4-ones (7a–d), respectively. Compounds (3,
6, and 7) have been cleaved by aromatic amines to give the correspond-
ing 2-(4ꢁ,5ꢁ-diaryl-2ꢁ,3ꢁ-dihydroimidazol-2ꢁ-yl)thioacetanilide (8a–f),
2-(2ꢁ,3ꢁ-dihydro-4ꢁ,5ꢁ-diaryl imidazol-2ꢁ-yl)thiopropionamide (9a–c),
and
3-(2ꢁ,3ꢁ-dihydro-4ꢁ,5ꢁ-diaryl-imidazol-2ꢁ-yl)thiopropionamide
(10a–d) respectively. All the prepared compounds show considerable
antimicrobial activity against bacteria, yeast, and fungi.
Keywords: 4,5-Diaryl-2-mercaptoimidazole derivatives
The chemistry of imidazole derivatives has received considerable at-
tention due to their biological activities.1−7 Accordingly, we have un-
dertaken the preparation of some new related derivatives for biological
evaluation.
Address correspondence to M. A. Salama, National Research Center, Dokki, Cairo,
Giza, Arab Republic of Egypt. E-mail: wagihhan@hotmail.com
305

306
M. A. Salama and L. A. Almotabacani
RESULTS AND DISCUSSION
Synthesis of new compounds were achieved by fusion of diaryl
benzoin8,9 with thiourea at 200◦C to give 2,3-dihydro-4,5-diaryl-2-
mercaptoimidazoles (2). The IR spectra of compounds (2) showed ab-
1
sorption bands arounds 3470-3080 cm−1. (cf. Table II). The H NMR
spectrum of (2a) [DMSO-d6] led to the following assignments: the
2NH protons as two broad singlets at δ = 9.36 and 9.26 (br., 2H,
2NH) and the aromatic protons as a multiplet (m, 8H, ArH’s) (cf.
Table II).
Compounds (2) were reacted with chlororacetic acid in acetic
acid/acetic anhydride in the presence of anhydrous sodium acetate
to produce 5,6-diaryl-2,3-dihydroimidazo[2,1-b]thiazol-3-ones (3); also
compounds (3) were prepared by the action of chloroacetyl chloride
on compounds (2) in presence of pyridine. The IR spectra of com-
pounds (3) showed the carbonyl absorption bands around 1700 cm−1
.
The 1H-NMR spectrum of compound (3a) [in DMSO-d6] showed a
methylene group as a singlet, (2H) at 3.25 ppm and the aromatic pro-
tons as a multiplet centred in the δ = 7.40-8.60 (m, 8H, ArH’s) (cf.
Table II).
The formulation of the cyclised products as (3) is favored over the
isomeric structures (3).10
Compounds (3) were condensed with aromatic aldehydes in acetic
acid/acetic anhydride mixture in the presence of anhydrous sodium
acetate to produce 2-arylmethylene-5,6-diaryl-2,3-dihydroimidazo[2,1-
b]-thiazol-3-ones (4a-q). The latter compounds were prepared directly
from (2) by the action of chloroacetic acid, aromatic aldehyde and
sodium acetate in acetic acid/acetic anhydride mixture. The reaction
product was found to be identical in all aspects (m.p., mixed m.p., and
IR) with (4). The IR spectra of compounds (4) showed carbonyl absorp-
tion around 1685–1700 cm−1. This shift to lower frequency is due to the
1
conjugation with the exocyclic double bond. The H-NMR spectrum of
(4a) [DMSO-d6] revealed the disappearance of the singlet at δ = 3.25
(compared with that of 3a) belonging to the activated methylene group,
besides the appearance of the expected signals at δ = 7.0–8.60 ppm
region (13H) for the aromatic protons and the benzylic proton (cf.
Table II).
Compounds (3) coupled with aryldiazonium salts in the presence of
pyridine to give 2-arylhydrazono-5,6-diaryl-2,3-dihydroimidazo[2,1-b]-
1
thiazol-3-ones (5). The presence of a peak at 2.70 and 3.70 pp in H-
NMR spectra, and the absence of NH-groups in compounds (5n) and
(5o) indicate that their coupling products exist in solution in the azo-
form11 (cf. Table II).

Mercaptoimidazole Derivatives
TABLE I Physical Data of Compounds 2–10
307
% Analysis (calcd./found)
Yield
(%)
Mol. form.
(mol. wt.)
m.p. ◦
Solvent
C
Comp.
Ar/Ar1
C
H
N
S
2a
o-C5H4N/
o-C5H4N
p-C5H4N/
p-C5H4N
p-C6H4F/
p-C6H4F
o-C6H4F/
C6H5
o-C4H3S/
o-C4H3S
o-C5H4N/
o-C5H4N
p-C6H4F/
p-C6H4F
o-C6H4F/
C6H5
o-C4H3S/
o-C4H3S
o-C5H4N/
o-C5H4N,
X = 4-Cl
o-C5H4N/
o-C5H4N,
X = 4-OMe
o-C5H4N/
o-C5H4N,
X = 2-NO2
o-C5H4N/
o-C5H4N,
X = 4-NO2
p-C6H4F/
p-C6H4F,
X = 4-Cl
p-C6H4F/
p-C6H4F,
X = 4-OMe
p-C6H4F/
p-C6H4F,
X = 2-NO2
p-C6H4F/
p-C6H4F,
X = 4-NO2
p-C6H4F/
p-C6H4F,
X = 4-Br
C6H5/
95
98
98
96
97
87
87
85
81
73
C13H10N4S
(254)
C13H10N4S
(254)
C13H10F2N2S
(288)
C13H11FN2S
(270)
C11H8N2S3
(264)
C15H10N4OS
(294)
C17H10F2N2OS
(328)
C17H11FN2OS
(310)
149
AcOH
215
DMF
150
AcOH
200
AcOH
95
AcOH
143
AcOH
108
EtOH/AcOH
90
64.41 3.93 22.04 12.59
61.82 3.90 22.00 12.35
61.41 3.93 21.04 12.59
62.50 3.97 21.90 12.72
2b
2c
2d
2e
3a
3b
3c
3d
4a
62.50 3.47
62.30 3.43
9.72 11.11
9.70 11.00
66.66 4.07 10.37 11.85
66.16 4.00 10.00 12.02
50.00 3.03 10.60 36.36
49.83 3.00 10.60 36.24
61.22 3.40 19.04 10.88
60.95 3.42 19.00 10.41
62.19 3.04
62.19 3.04
65.80 3.54
65.55 3.24
51.31 2.63
51.20 2.43
8.53
8.52
9.03 10.32
9.03 10.36
9.21
9.21
9.75
9.75
EtOH
240
AcOH
160
C13H8N2OS3
(304)
C22H13ClN4OS
(416.5)
31.57
31.57
7.68
63.38 3.12 13.44
63.05 3.12 13.43
AcOH
7.65
4b
4c
4d
4e
4f
69
56
75
85
76
71
87
80
87
75
C23H16N4O2S
(412)
280
AcOH
66.99 3.88 13.59
67.24 3.90 13.59
7.76
7.54
C22H13N5O3S
(427)
192
61.82 3.04 16.39
61.69 2.98 16.21
7.49
7.49
Benzene/pet.
ether 40–60◦C
172
C22H13N5O3S
(427)
61.82 3.04 16.39
61.69 2.98 16.21
7.49
7.49
CHCl3/pet.
ether 40–60◦C
C24H13ClF2N2OS 170
(450.5)
63.92 2.88
63.70 2.80
6.21
6.20
7.10
7.10
AcOH
C25H16F2N2O2S
(446)
150
EtOH
76.26 3.58
76.00 3.50
6.27
6.27
7.17
7.15
4g
4h
4i
C24H13F2N3O3S
(461)
110
62.47 2.81
62.47 2.97
9.11
9.11
6.94
6.82
CHCl3/pet.
ether 40–60◦C
235
C24H13F2N3O3S
(461)
62.47 2.81
62.47 2.60
9.11
9.00
6.94
6.72
CHCl3/pet.
ether 40–60◦C
C
24H13BrF2N2OS 158
58.19 2.62
57.87 2.42
5.65
5.65
6.46
6.73
(494.9)
CHCl3/pet.
ether 40–60◦C
160
4j
C24H14ClFN2OS
(432.5)
66.58 3.23
66.92 3.43
6.47
6.47
7.39
7.35
o-C6H4F,
X = 4-Cl
C6H5/
o-C6H4F,
X = 4-OMe
AcOH
4k
C
25H17FN2O2S
140
EtOH
70.09 3.97
70.00 3.90
6.54
6.54
7.47
7.32
(428)
(Continued on next page)

308
M. A. Salama and L. A. Almotabacani
TABLE I Physical Data of Compounds 2–10 (Continued)
% Analysis (calcd./found)
Yield
(%)
Mol. form.
(mol. wt.)
m.p. ◦
Solvent
C
Comp.
Ar/Ar1
C6H5/
C
H
N
S
4l
78
81
73
77
79
82
63
87
79
85
75
76
89
81
93
79
86
C24H14FN3O3S
(443)
120
MeOH
65.01 3.16
64.98 3.03
9.48
9.24
7.22
7.22
o-C6H4F,
X = 2-NO2
C6H5/
4m
4n
4o
4p
4q
5a
5b
5c
5d
5e
5f
C24H14FN3O3S
(443)
132
MeOH
65.01 3.16
65.01 2.98
9.48
9.41
7.22
7.00
o-C6H4F,
X = 4-NO2
o-C4H3S/
o-C4H3S
X = 4-Cl
o-C4H3S/
o-C4H3S,
X = 4-OMe
o-C4H3S/
o-C4H3S,
X = 2-NO2
o-C4H3S/
o-C4H3S,
X = 4-NO2
o-C5H4N/
o-C5H4N,
X = H
C20H11ClN2OS3
(426.5)
190
DMF
56.27 2.57
56.22 2.32
6.56 22.50
6.56 22.00
C21H14N2O2S3
(422)
245
DMF
59.71 3.31
59.21 2.28
6.63 22.74
6.92 22.93
C20H11N3O3S3
(437)
212
54.91 2.51
54.82 2.32
9.61
9.64
21.96
22.34
CHCl3/pet.
ether 40–60◦C
182
CHCl3/pet.
ether 40–60◦C
230
C20H11N3O3S3
(437)
54.91 2.51
54.91 2.45
9.61 21.96
9.48 22.73
C21H14ClN6O3S
(398)
63.31 3.51 21.10
63.00 3.50 21.00
8.04
8.31
AcOH
o-C5H4N/
o-C5H4N,
X = 4-NO2
o-C5H4N/
o-C5H4N,
X = 2-NO2
o-C5H4N/
o-C5H4N,
X = 4-Br
o-C5H4N/
o-C5H4N,
X = 4-Cl
o-C5H4F/
o-C5H4F,
X = H
C21H13N7O3S
(443)
118
AcOH
56.88 2.93 22.12
56.42 2.81 22.44
7.22
7.57
C21H13N7O3S
(443)
110
56.88 2.93 22.12
56.71 2.92 22.19
7.22
7.24
CHCl3/pet.
ether 40–60◦C
117
C21H13BrN6OS
(476.9)
52.84 2.72 17.61
52.95 2.77 17.94
6.71
6.79
AcOH
C21H13ClN6OS
(432.5)
276
AcOH
58.26 3.00 19.42
58.62 3.10 19.71
7.39
7.75
C23H14F2N4OS
(432)
108
63.88 3.24 12.96
63.95 3.31 13.24
7.40
7.76
CHCl3/pet.
ether 40–60◦C
98
5g
5h
5i
o-C5H4F/
o-C5H4F,
X = 4-NO2
o-C5H4F/
o-C5H4F,
X = 2-NO2
o-C5H4F/
o-C5H4F,
X = 4-Br
o-C5H4F/
o-C5H5,
C23H13F2N5OS
(477)
57.86 2.72 14.67
57.79 2.72 14.61
6.70
6.92
MeOH
C23H13F2N5OS
(477)
110
MeOH
57.86 2.72 14.67
57.52 2.70 14.65
6.70
6.96
C
23H13F2BrN4OS 128
54.02 2.54 10.96
53.87 2.78 10.89
6.26
6.54
(510.9)
MeOH
5j
C23H15FN4OS
(414)
112
AcOH
66.66 3.62 13.52
66.61 3.62 13.27
7.72
7.62
X = H
5k
o-C5H4F/
C5H5,
C23H14FN5O3S
(459)
190
60.13 3.05 15.25
59.86 3.00 15.25
6.97
6.81
Benzene/pet.
X = 4-NO2
ether 40–60◦C
(Continued on next page)

Mercaptoimidazole Derivatives
309
TABLE I Physical Data of Compounds 2–10 (Continued)
% Analysis (calcd./found)
Yield
(%)
Mol. form.
(mol. wt.)
m.p. ◦
Solvent
C
Comp.
Ar/Ar1
C
H
N
S
5l
o-C5H4F/
C5H5,
X = 2-NO2
o-C5H4F/
o-C5H5,
X = 4-Br
o-C4H3S/
o-C4H3S,
X = H
83
90
65
73
77
81
67
C23H14FN5O3S
(459)
190
60.13 3.05 15.25
60.34 3.22 15.18
6.97
6.99
Benzene/pet.
ether 40–60◦C
5m
5n
5o
5p
5q
5r
C23H14BrFN4O3S 147
(492.9)
55.99 2.84 11.36
56.17 2.89 11.36
6.49
6.75
MeOH
C19H12N4OS3
(408)
156
55.88 2.94 13.72 23.52
55.62 2.92 13.72 23.20
Benzene/pet.
ether 40–60◦C
163
CHCl3/pet.
ether 40–60◦C
108
CHCl3/pet.
ether 40–60◦C
175
Benzene/pet.
ether 40–60◦C
128
CHCl3/pet.
ether 40–60◦C
132
Pyridine
140
AcOH
83
EtOH
145
CHCl3
118
Pyridine
95
AcOH
o-C4H3S/
o-C4H3S,
X = 4-NO2
o-C4H3S/
o-C4H3S,
X = 2-NO2
o-C4H3S/
o-C4H3S,
X = 4-Br
o-C4H3S/
o-C4H3S,
X = 4-Cl
o-C5H4N/
o-C5H4N
p-C6H4F/
p-C6H4F
p-C6H4F/
C6H5
o-C4H3S/
o-C4H3S
o-C5H4N/
o-C5H4N
p-C6H4F/
p-C6H4F
p-C6H4F/
C6H5
C19H11N5O3S3
(453)
50.33 2.42 15.54 21.19
50.31 2.42 15.43 21.25
C19H11N5O3S3
(453)
50.33 2.42 15.54 21.19
50.48 2.51 15.45 21.23
C19H11BrN4OS3
(486.9)
46.82 2.25 11.50 19.71
46.75 2.25 11.35 19.50
C19H11ClN4OS3
(442.5)
51.52 2.48 12.65 21.69
51.80 2.34 12.63 21.87
6a
6b
6c
6d
7a
7b
7c
7d
65
91
89
76
57
82
74
69
C16H12N4OS
(308)
C18H12F2N2OS
(342)
C18H13FN2OS
(324)
C14H10N2OS3
(318)
C16H12N4OS
(308)
C18H12F2N2OS
(342)
C18H13FN2OS
(324)
C14H10N2OS3
(318)
62.33 3.89 18.18 10.38
62.17 3.85 18.16 10.71
63.15 3.50
63.11 3.51
66.66 4.01
66.94 3.97
52.83 3.14
52.94 3.21
8.18
8.24
8.64
8.51 10.13
8.80 30.18
8.78 30.00
9.35
9.30
9.87
62.33 3.89 18.18 10.38
62.00 3.71 18.20 10.87
63.15 3.50
63.00 3.71
66.66 4.01
66.96 3.89
52.83 3.14
52.71 3.31
8.18
8.42
8.64
8.51
8.80 30.18
8.71 30.43
9.35
9.31
9.87
9.91
97
EtOH
152
CHCl3/pet.
ether 40–60◦C
128
EtOH
95
o-C4H3S/
o-C4H3S
8a
8b
8c
o-C5H4N/
o-C5H4N
p-C6H4F/
p-C6H4F
p-C6H4F/
p-C6H4F,
4-NO2
89
98
92
C21H17N5OS
(387)
C23H17F2N3OS
(421)
C23H16F2N4O3S
(466)
65.11 4.39 18.08
64.86 4.31 18.00
8.26
8.45
7.60
7.51
6.86
6.89
65.55 4.03
65.50 3.85
9.97
9.72
AcOH
172
MeOH
59.22 3.43 12.01
59.00 3.41 12.37
8d
8e
p-C6H4F/
C6H5
p-C6H4F/
C6H5,4-NO2
93
88
C23H18FN3OS
(403)
C23H17FN4O3S
(448)
105
EtOH
178
68.48 4.46 10.42
68.91 4.53 10.41
61.60 3.79 12.50
61.42 3.71 12.30
7.94
8.12
7.14
7.14
AcOH
(Continued on next page)

310
M. A. Salama and L. A. Almotabacani
TABLE I Physical Data of Compounds 2–10 (Continued)
% Analysis (calcd./found)
Yield
(%)
Mol. form.
(mol. wt.)
m.p. ◦
Solvent
C
Comp.
Ar/Ar1
C
H
N
S
8f
o-C4H3S/
o-C4H3S
91
C19H15N3OS3
(397)
135
57.43
57.00
3.77
3.72
10.57
10.23
24.18
24.58
CHCl3/pet.
ether 40–60◦C
122
CHCl3/pet.
ether 40–60◦C
98
9a
o-C5H4N/
o-C5H4N
92
C22H19N5OS
(401)
65.83
65.55
4.73
4.71
17.45
17.09
7.98
7.67
9b
9c
p-C6H4F/
p-C6H4F
o-C6H4F/
C6H5
98
97
C24H19F2N3OS
(435)
C24H20FN3OS
(417)
66.20
66.00
69.06
69.04
4.36
4.32
4.79
4.78
9.65
9.63
10.07
10.00
7.35
7.35
7.67
7.83
AcOH
92
Benzene/pet.
ether 40–60◦C
210
CHCl3/pet.
ether 40–60◦C
110
AcOH
148
Benzene/pet.
ether 40–60◦C
135
10a
o-C5H4N/
o-C5H4N
89
C22H19N5OS
(401)
65.83
65.92
4.73
4.71
17.45
17.61
7.98
7.92
10b
10c
p-C6H4F/
p-C6H4F
o-C6H4F/
C6H5
97
93
C24H19F2N3OS
(435)
C24H20FN3OS
(417)
66.20
66.08
69.06
69.00
4.36
4.31
4.79
4.45
9.65
9.25
10.07
9.73
7.35
7.11
7.67
7.15
10d
o-C4H3S/
o-C4H3S
95
C20H17N3OS3
(411)
58.39
58.80
4.13
4.13
10.21
10.25
23.35
22.87
CHCl3/pet.
ether 40–60◦C
Compounds (2) was reacted with 2- or 3-bromopropanoic acid in
refluxing acetic acid/acetic anhydride mixture to produce 5,6-diaryl-
2,3-dihydro-2-methylimidazo[2,1-b]thiazol-3-ones (6) and 6,7-diaryl-
2,3-dihydroimidazo[2,1-b]-1,3-thiazin-4-ones (7) respectively. The IR
spectra of compounds (6) showed absorption around 1710–1750 cm−1
(C O) and the 1H-NMR spectrum of compound (6a) [DMSO-d6] showed
the following peaks in δ ppm: a doublet at δ 1.8 (3H) for the methyl
group, quartet at δ 2.3 (1H) for (CH) of the thiazole ring and a multiplet
at δ 7.30–8.70 region (8H) for the aromatic protons (cf. Table II).
The IR spectra of compounds (7) showed absorption band at
1700 cm−1 (C O) and the 1H-NMR spectrum of compound (7a) [DMSO-
d6 + CDCl3] showed the following assignments in δ ppm, a multiplet
centered at δ = 2.60–3.40 (4H, thiazin protons) and at δ 7.30–8.70 (m,
8H, Ar’s) (cf. Table II).
Compounds (3, 6, and 7) have been cleaved by aniline to give the cor-
responding
2-(4ꢁ,5ꢁ-diaryl-2ꢁ,3ꢁ-dihydroimidazol-2ꢁ-yl)thioacetanilide
(8), 2-(4ꢁ,5ꢁ-diaryl-2ꢁ,3ꢁ-dihydroimidazol-2ꢁ-yl)thiopropionamide (9), and
3-(4ꢁ,5ꢁ-diaryl-2ꢁ,3ꢁ-dihydroimidazol-2ꢁ-yl)thiopropionamide derivatives
(10) respectively. Compounds (8, 9, and 10) showed correct values in
elemental analyses as well as the expect IR peaks. 1H-NMR [DMSO-d6]

Mercaptoimidazole Derivatives
311
TABLE II IR and 1H-NMR Spectral Data of Compounds 3–10
1H-NMR
IR
Comp.
No.
ν [cm−1
]
Solvent
Aa
[δ ppm]
2a
3160, 3470
(br., NH),
9.36–9.56 (br., 2H, 2NH); 7.2–9.0 (m, 8H, ArH’s)
1260 (C S)
3150 (br., NH),
1220 (C S)
3080, 3120
(br., NH),
2b
2c
A
A
3.3 (br., 1H, NH), 5.6 (br., 1H, NH);
7.0–8.6 (m, 8H, ArH’s)
4.2 (s, 1H, NH), 5.9 (s, 1H, NH);
6.65–8.20 (m, 8H, ArH’s)
1260 (C S)
3100 (br., NH),
1220 (C S)
3080 (br., NH),
1220 (C S)
1710 (C O),
2925 (CH2)
1700 (C O),
2920 (CH2)
1700 (C O),
2930 (CH2)
1700 (C O),
2920 (CH2)
1700 (C O)
1675 (C O),
2910 (CH3)
1690 (C O)
1685 (C O)
1700 (C O)
1700 (C O),
2920 (CH3)
1740 (C O)
1740 (C O)
1680 (C O)
1730 (C O)
1700 (C O),
2940 (CH3)
1740 (C O)
1730 (C O)
1690 (C O)
2d
2e
3a
3b
3c
3d
A
A
A
A
A
A
43.10 (br., 1H, NH), 6.8–8.4 (m, 9H, ArH’s);
12.4 (br., 1H, NH)
3.3 (br., 2H, 2NH); 6.60–8.00 (m, 6H, Ar’H)
3.25 (s, 2H, CH2); 7.4–8.6 (m, 8H, ArH’s)
3.75 (s, 2H, CH2); 7.0–7.75 (m, 8H, ArH’s)
3.50 (s, 2H, CH2); 7.1–8.3 (m, 9H, ArH’s)
3.5 (s, 2H, CH2); 6.9–8.3 (m, 6H, thiophene
protons)
7.0–8.6 (m, 13H, Ar’s and benzilic proton)
3.8 (s, 3H, OCH3); 7.06–9.1 (m, 13H, ArH’s and
benzilic proton)
7.4–8.6 (m, 13H, ArH’s and and benzilic proton)
7.8–8.7 (m, 13H, ArH’s and benzilic proton)
6.8–8.0 (m, 13H, ArH’s and benzilic proton)
3.3 (s, 3H, OCH3); 7.1–7.9 (m, 13H, ArH’s and
benzilic proton)
6.9–8.2 (m, 13H, ArH’s and benzilic proton)
7.0–8.4 (m, 13H, ArH’s and benzilic proton)
7.1–8.0 (m, 13H, ArH’s and benzilic proton)
6.9–8.2 (m, 13H, ArH’s and benzilic proton)
3.8 (s, 3H, OCH3); 7.00–8.0 (m, 14H, ArH’s and
benzilic proton)
4a
4b
A
A
4c
4d
4e
4f
A
A
Bb
A
4g
4h
4i
4j
4k
A
B
B
A
A
4l
4m
4n
A
A
B
7.2–8.4 (m, 14H, ArH’s and benzilic proton)
6.09–8.0 (m, 14H, ArH’s and benzilic proton)
6.9–8.0 (m, 11H, ArH’s, thiophene protons and
benzilic proton)
4o
4p
4q
5a
1690 (C O),
2920 (OCH3)
1685 (C O)
A
A
B
A
3.9 (s, 3H, OCH3); 7.00–7.9 (m, 11H, ArH’s,
thiophene protns and benzilic proton)
7.1–8.2 (m, 11H, ArH’s, thiophene protns and
benzilic proton)
6.8–7.9 (m, 11H, ArH’s, thiophene protns and
benzilic proton)
1690 (C O)
1690 (C O),
7.0–8.5 (m, 13H, ArH’s); 9.4 (s, 1H, NH)
3100 (br., NH)
(Continued on next page)

312
M. A. Salama and L. A. Almotabacani
TABLE II IR and 1 H-NMR Spectral Data of Compounds 3–10 (Continued)
1H-NMR
IR
Comp.
No.
ν [cm−1
]
Solvent
A
[δ ppm]
5b
5c
5d
5e
5f
1680 (C O),
3250 (br., NH)
1680 (C O),
3150 (br., NH)
1680 (C O),
3280 (br., NH)
1685 (C O),
6.6–9.0 (m, 12H, ArH’s); 10.04 (s, 1H, NH)
A
A
6.6–9.4 (m, 12H, ArH’s); 11.8 (s, 1H, NH)
3.31 (s, 1H, NH); 6.6–8.7 (m, 12H, ArH’s)
6.8–8.2 (m, 12H, ArH’s); 10.4 (s, 1H, NH)
3.39 (br., 1H, NH); 6.6–7.8 (m, 13H, ArH’s)
3.2 (br., 1H, NH); 6.8–8.7 (m, 12H, ArH’s)
3.3 (br., 1H, NH); 6.6–8.0 (m, 12H, ArH’s)
A
3230 (br., NH)
1680 (br., C O),
3050 (br., NH)
1700 (br., C O),
3050 (br., NH)
1710 (br., C O),
3060 (br., NH)
1680 (br., C O),
3050 (br., NH)
1700 (br., C O),
3050 (br., NH)
1700 (br., C O),
3100 (br., NH)
1700 (br., C O),
3080 (br., NH)
1680 (br., C O),
3050 (br., NH)
1700 (br., C O)
A
5g
5h
5i
A
A
A
3.2 (br., 1H, NH); 6.9–7.8 (m, 12H, ArH’s);
9.4 (s, 1H, NH)
2.3 (br., 1H, NH); 6.8–7.8 (m, 14H, ArH’s)
5j
A
5k
5l
B
2.3 (br., 1H, NH); 6.6–7.8 (m, 13H, ArH’s)
2.3 (br., 1H, NH); 6.5–8.0 (m, 13H, ArH’s)
3.5 (br., 1H, NH); 6.6–7.8 (m, 13H, ArH’s)
B
5m
5n
5o
5p
5q
5r
6a
6b
6c
6d
7a
7b
A
A
2.7 (s, 1H, CH); 6.2–8.0 (m, 11H, ArH’s and
thiophene protons)
3.4 (s, 1H, CH); 6.8–8.5 (m, 10H, ArH’s and
thiophene protons)
3.85 (br., 1H, NH); 6.8–8.5 (m, 10H, ArH’s
and thiophene protons)
6.7–8.0 (m, 10H, ArH’s and thio-phene
protons); 8.7 (br., 1H, NH)
3.5 (br., 1H, NH); 6.7–8.9 (m, 10H, ArH’s and
thiophene protons)
1.8 (d, 3H, CH3); 2.3 (q, 1H, CH);
7.3–8.7 (m, 8H, ArH’s)
1.5 (d, 3H, CH3); 2.3 (q, 1H, CH);
6.6–8.4 (m, 8H, ArH’s)
1.7 (d, 3H, CH3); 2.3 (q, 1H, CH);
6.6–8.2 (m, 9H, ArH’s)
1700 (br., C O)
A
1700 (br., C O),
3090 (br., NH)
1650 (br., C O),
3100 (br., NH)
1685 (C O),
3150 (br., NH).
1710 (C O),
2910 (CH3)
1750 (C O),
2930 (CH3)
1710 (C O),
2920 (CH3)
B
B
A
B
A
A
1710 (C O),
2920 (CH3)
1700 (C O)
A
1.7 (d, 3H, CH3); 2.4 (q, 1H, CH);
6.8–8.2 (m, 6H, thiophene protones)
2.6–3.4 (m, 4H, thiazine protons);
7.3–8.7 (m, 8H, ArH’s)
3.9–4.5 (m, 4H, thiazine protons);
6.9–7.3 (m, 8H, ArH’s)
A+B
B
1700 (C O)
(Continued on next page)

Mercaptoimidazole Derivatives
313
TABLE II IR and 1 H-NMR Spectral Data of Compounds 3–10 (Continued)
1H-NMR
IR
Comp.
No.
ν [cm−1
]
Solvent
B
[δ ppm]
7c
7d
8a
1700 (C O)
1700 (C O)
1.8–3.3 (m, 4H, thiazine protons);
6.6–8.1 (m, 9H, ArH’s)
2.75 (m, 2H, thiazine protons);
6.5–8.0 (m, 6H, ArH’s)
1.8 (s, 1H, NH); 3.2 (s, 2H, CH2);
6.4–8.8 (m, 13H, ArH’s); 10.6 (s, 1H, NH)
B
A
1700 (C O), 3040
(NH), 3400 (NH),
2920 (CH2)
8b
8c
1680 (C O),
3090 (br., NH),
2916 (CH2)
1680 (C O),
3280 (NH),
B
A
B
A
B
A
B
B
A
B
B
A
3.6 (s, 1H, NH); 3.8 (s, 2H, CH2);
6.7–8.4 (m, 13H, ArH’s); 10.7 (s, 1H, NH)
3.4 (s, 1H, NH); 3.9 (s, 2H, CH2);
6.9–8.2 (m, 12H, ArH’s); 10.5 (s, 1H, NH)
2920 (CH2)
8d
1680 (C O), 3060
(NH), 3390 (br.,
NH), 2915 (CH2)
1680 (C O), 3100
(NH), 3280 (NH),
2920 (CH2)
1670 (C O), 3080
(NH), 3350 (NH),
2915 (CH2)
3.5 (s, 1H, NH); 4.0 (s, 2H, CH2);
6.8–8.0 (m, 14H, ArH’s); 10.2 (s, 1H, NH)
8e
2.5 (s, 1H, NH); 3.35 (s, 2H, CH2);
7.2–8.2 (m, 13H, ArH’s); 10.5 (s, 1H, NH)
8f
1.4 (s, 1H, NH); 1.9 (s, 1H, NH);
4.3 (s, 2H, CH2); 5.0–8.0 (m, 11H, ArH’s
and thiophene protons)
1.2 (d, 3H, CH3); 2.9 (s, 1H, NH);
3.5 (q, 1H, CH); 7.0–8.2 (m, 13H, ArH’s);
8.7 (s, 1H, NH)
1.6 (d, 3H, CH3); 2.6 (s, 1H, NH);
4.2 (q, 1H, CH); 6.8–7.5 (m, 13H, ArH’s);
8.1 (s, 1H, NH)
1.5 (d, 3H, CH3); 2.15 (s, 1H, NH); 4.25 (q,
1H, CH); 6.7–7.8 (m, 14H, ArH’s); 8.2 (s,
1H, NH)
9a
1630 (C O),
3060 (br., NH),
3400 (br., OH)
1740 (C O),
9b
3050 (br., NH)
9c
1740 (C O),
3060 (br., OH)
10a
10b
10c
10d
1690 (C O),
1.3 (s, 1H, NH); 2.5–3.6 (m, 4H, 2CH2);
6.5–7.8 (m, 13H, ArH’s); 8.7 (s, 1H, NH)
3060 (br., NH),
3400 (br., OH)
1700 (C O),
3040 (br., NH),
3400 (br., OH)
1715 (C O),
3060 (br., NH),
3400 (br., OH)
1680 (C O),
3040 (br., NH),
3400 (br., OH)
1.25 (s, 1H, NH); 2.1–3.0 (m, 4H, 2CH2);
6.7–8.0 (m, 13H, ArH’s); 8.4 (s, 1H, NH)
1.4 (s, 1H, NH); 3.2–3.9 (m, 4H, 2CH2);
6.7–7.8 (m, 14H, ArH’s); 9.0 (s, 1H, NH)
1.4 (s, 1H, NH); 3.0–3.7 (m, 4H, 2CH2);
6.8–7.8 (m, 11H, ArH’s); 8.0 (s, 1H, NH)
aA = DMSO-d6.
bB = CDCl3.

314
M. A. Salama and L. A. Almotabacani
of compound (8a) as an example, showed signals at δ 1.80 ppm (s, 1H,
NH), δ 3.20 ppm (s, 2H, CH2), δ 6.40-8.80 ppm (m, 13H, ArH’s), and δ
10.60 ppm (s, 1H, NH) (cf. Table II).
The structures of the new compounds were established by chemi-
1
cal analysis, mass spectra, H-NMR and IR spectra. Physical data of
compounds (2–20) are given in (Table I and II).
Antimicrobial Activity
The antimicrobial activity of the compounds considered was tested
on Bacillus subtilis, Staphylocoucus aureus, Escherichia Coli, Proteus
mirabilis, Candida albicans, and Aspergillus niger. The biological ac-
tivity was determined according to the cup plate method.12 The sensi-
tivity of microorganisms to the compound is identified in the following
manner:
(++++) = highly sensitive (inhibition zone > 15 mm);
(+++) = fairly sensitive (inhibition zone > 12 mm);
(++) = slightly sensitive (inhibition zone > 9 mm);
(+) = very slightly sensitive (inhibition zone > 6 mm).
It could be mentioned that, the most determined effect is brought
about by compounds 4i, 4o, 4f, 4r, 5d, 5i, 5j, 5k, 5o, 5p, 5r, 7d, 9a, and
10d (Table III).
EXPERIMENTAL
All melting points uncorrected. The 1H-NMR spectra were recorded
on a Varian 1H, Gemini 200 Spectrometer (National Research Centre,
Egypt) and chemical shifts were expressed as δ-value against TMS as
internal standard. The IR spectra (KBr) were recorded on a Perkin-
Elmer 1430 Spectrometer (Cairo Univesity). The mass spectra were
recorded on Finnigan SSQ 7000 Spectrometer. Microanalytical data
performed by the Microanalytical Center at the Faculty of Science, Cairo
University.
4,5-Diaryl-2,3-dihydro-2-mercaptoimidazoles 2a---e
Compounds 2 were prepared from disubstituted benzoin13−15 deriva-
1
tives, by fusion with thiourea at 200◦C.10 Physical data, IR, and H-
NMR spectra (Tables I and II).

315

316
M. A. Salama and L. A. Almotabacani
5,6-Diaryl-2,3-dihydro-2-mercaptoimidazo[2,1-b]thiazol-
3-ones 3a---d
Method A
A mixture of compounds 2 (0.01 mmol) and chloroacetic acid (0.01
mmol) and 2 g of fused anhyd. Sodium acetate in 15 mL of acetic acid
and 7 mL of acetic anhydride was refluxed for 3 h and left to cool. The
reaction mixture was poured onto water. The solid obtained was filtered
off and crystallized from the proper solvent (Tables I and II).
Method B
Chloroacetyl chloride (0.01 mmol), was added gradually while stir-
ring to a cooled solution of compound 2 (0.01 mmol) in 30 mL pyridine.
The reaction mixture was left while cooling for 1 h, then poured into
cold water, filtered and crystallised from the proper solvent (Tables I
and II).
2-Arylmethylene-5,6-diaryl-2,3-dihydroimidazo[2,1-b]-
thiazol-3-ones 4a---q
Method A
A mixture of compound 3 (0.01 mmol), aromatic aldehyde (0.01 mmol)
in a mixture of glacial acetic acid (20 mL) and acetic anhydride (10 mL)
in the presence of anhydrous sodium acetate was refluxed for 2 h. Af-
ter cooling, water was added and the precipitate was filered off and
crystallized from the proper solvent (Tables I and II).
Method B
A mixture of compounds 2 (0.01 mmol), chloroacetic acid (0.01 mmol),
aromatic aldehyde and 2 g of anhydrous sodium acetate in a mixture of
20 mL acetic acid/10 mL acetic anhydride was refluxed for 1 h. It was
cooled and then poured onto water. The solid obtained was filtered off
and crystallized from the proper solvent (Tables I and II).
2-Arylhydrazono-5,6-diaryl-2,3-dihydroimidazo[2,1-b]-
thiazol-3-ones 5a---r
The aromatic amine (0.01 mmol) was dissolved in 3 mL of conc. HCl acid
and 2 mL of water, cooled to –10◦C and treated with 0.07 g of sodium
nitrile in 3 mL of water. The diazotized amine was added gradually
while stirring to cold solution of compound 3 (0.01 mmol) in 15 mL of
pyridine. The reaction mixture was cooled for 30 min. The product was
filtered off and crystallized from the proper solvent (Tables I and II).

Mercaptoimidazole Derivatives
317
TABLE III Antimicrobial Screening for the Selected Compounds Against
Bacteria, Yeast and Fungi
B.
S.
E.
P.
C.
A.
Comp.
subtilis
aureus
coli
mirabilis
allbicans
niger
Controla
1c
2d
3a
3b
3c
4a
4d
4e
4f
4g
4h
4i
++++
+
+++++
+
+++
−
+++
−
++
+
++
+
+
+
−
−
+
+
++
+
++
+
+
+
++
+
++
+
−
−
+
+
−
−
+
+
++
++
++
+
++
++
++
+
++
++
+
++
++
+
++
++
++
++
+
++
++
++
++
+
+
+
++
++
++
+++
++
+++
++
+
++
++
++
+++
++
+++
++
+
+
+
+
+
++
+
++
+
+
+
4j
+
+
++
++
+
++
++
+
4k
4o
4p
4q
4r
5d
5f
5g
5h
5i
+
+
+
+
+
+
+
+
+
+
+++
+++
+++
++
++
+
+++
+++
+++
++
++
+
+
+
+
+
++
++
++
++
+++
++
++
++
++
++
+
++
++
++
++
+++
++
++
++
++
++
+
++
+
++
+
+
+
+
+
+
+
+++
+++
+++
++
+
+++
+++
+++
++
+
5j
5k
5l
+
+
++
+
+++
+
5n
5o
5p
5q
5r
6a
6b
6c
7a
7b
7c
7d
8b
8c
8d
8e
8f
9a
9b
10a
10d
+
+
++
+
++
+
+++
+++
+++
+++
++
+
+++
+++
+++
+++
++
+
+
+
+
+
+++
++
+
+++
++
+
++
++
−
++
++
−
++
++
+
++
++
+
+
+
+
+
++
−
++
−
++
+
++
+
+
+
−
−
+
+
++
++
+
++
++
+
+
+
+++
++
+
+++
++
+
++
−
++
−
+
+
−
−
+
+
+
+
−
−
+
+
+
+
+
+
+
+
+++
+
+++
+
++
−
++
−
+++
+
+++
+
+
+
−
−
+
+
++
++
+
+
+++
+++
aControl Ampicillin.

318
M. A. Salama and L. A. Almotabacani
5,6-Diaryl-2,3-dihydro-2-methylimidazo[2,1-b]-
thiazol-3-ones 6a---d
Compounds 6 were prepared by the same method used for compounds 3,
but by using 2-bromopropionic acid instead of chloroacetic acid (Tables I
and II).
6,7-Diaryl-1,3-thiazino[3,2-a]imidazol-4-ones 7a---d
Compounds 7 were prepared by the same method use for compounds 3
but by using 3-bromopropionic acid instead of chloroacetic acid (Tables I
and II).
2(4ꢀ ,5ꢀ -diaryl-2ꢀ ,3ꢀ -dihydroimidazo-2ꢀ -yl thio)acetanilide
Derivatives 8a---f
Compounds 3 (0.005 mmol) and (0.006 mmol) of the aromatic amine
were refluxed in 15 mL of ethanol for 2 h. The reaction mixture was
allowed to cool then poured into water. The solid product formed was
collected, washed with little ethanol and crystallized from the proper
solvent (Tables I and II).
2-(4ꢀ ,5ꢀ -Diaryl-2ꢀ ,3ꢀ -dihydroimidazol-2ꢀ -yl)-
thiopropionamide Derivatives 9a---c
Compounds 9 were prepared by the same method used for compounds
8 (Tables I and II).
3-(4ꢀ ,5ꢀ -Diaryl-2ꢀ ,3ꢀ -dihydroimidazol-2ꢀ -yl)-
thiopropionamide 10a---d
Compounds 10 were prepared by the same method used for compounds
8 (Table I and II).
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Mercaptoimidazole Derivatives
319
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