Synthesis, characterization, and in vitro antimicrobial activity of methyleneamine-linked bis-heterocycles

Article abstract of DOI:10.1002/jhet.1674

A new class of methyleneamine-linked bis-heterocycles that exhibit antimicrobial activity was synthesized. Bromination of 1 followed by condensation with thiourea gave 3. The reaction of 3 with propargyl bromide in dry toluene under inert atmosphere led t

Full text of DOI:10.1002/jhet.1674

May 2013
Synthesis, Characterization, and In Vitro Antimicrobial Activity of
727
Methyleneamine-Linked Bis-heterocycles
A. Babulreddy, R. V. Hymavathi, Md. Manzoor Hussain, and G. Narayana Swamy *
1
,3
2
3
3
1
Department of Molecular Science and Technology, Ajou University, San 5, Woncheon-dong, Yeongtong, Suwon 443-749,
South Korea
2
Department of Bio-Chemistry, Sri Krishnadevaraya University, Anantapur 515003, Andhra Pradesh, India
3
Department of Chemistry, Sri Krishnadevaraya University, Anantapur 515003, Andhra Pradesh, India
*
E-mail: narayanaswamy.golla@gmail.com
Received August 20, 2011
DOI 10.1002/jhet.1674
Published online in Wiley Online Library (wileyonlinelibrary.com).
A new class of methyleneamine-linked bis-heterocycles that exhibit antimicrobial activity was synthesized.
Bromination of 1 followed by condensation with thiourea gave 3. The reaction of 3 with propargyl bromide
in dry toluene under inert atmosphere led to the formation of 4. Its subsequent reaction with different nitrile
oxides using CuSO .5H O–sodiumascorbate system in a 2:1 mixture of water and tert-butyl alcohol yielded
4
2
the title compounds 6a–l in good yields. The identities of these compounds were confirmed following elemental
1
13
analysis, IR, H, C NMR, and mass spectral studies. All the title compounds exhibited pronounced in vitro
antibacterial and antifungal activities.
J. Heterocyclic Chem., 50, 727 (2013).
INTRODUCTION
[12], antibacterial [13], and immunomodulating activities
[14], and have also been used as dyes, electric-insulating
The development of simple, facile, and efficient synthetic
methods for synthesis of five-membered heterocycles from
readily available reagents is one of the major challenges in
organic synthesis. Among five-membered heterocycles,
isoxazole and thiazoles represent a class of compounds of
great importance in biological chemistry. Bis-heterocyclic
compounds with suitable alkyl spacer constitute an impor-
tant class and have been under study for various types of
activities, preferably antitumor [1] and antimicrobial [2],
based on the DNA-binding affinity and enzyme-inhibiting
actions. For instance, isoxazole-containing natural and
non-natural compounds are interesting because of their
biological activities [3] as fungicides [4], herbicides [5],
or as nicotinic acetylcholine receptor ligands [6], and also
isoxazoles have long been targeted in synthetic investiga-
tions for their known biological activities and pharmacolog-
ical properties, which includes hypoglycemic[7], analgesic
oils, and high-temperature lubricants [15–24]. Thiazole
derivatives were gaining synthetic interest in recent years
due to their broad spectrum of biological activities, and
molecules containing thiazole ring system are extensively
found in the field of agrochemicals [25], such as commer-
cial agricultural fungicides trifluzamide and ethaboxam
[26]. Because of its low toxicity, excellent biological
activity, as well as ready access of diverse derivatives, this
class of N-heterocyclic derivatives is widely studied [27].
Hence, it is thought that a worthwhile program would be
required to prepare molecules having both isoxazole and
thiazole rings through the most popular method following
1,3-dipolar cycloaddition reaction of nitrile oxides with
terminal alkynes [28]. There are several reports in the
literature for the synthesis of various combinations of bis-
heterocycles, but no reports are available for the synthesis
of bis-heterocycles encompassing isoxazole and thiazole
moieties. We, therefore, followed a convenient and
[8], anti-inflammatory [9,10], antiviral [11], antitubulin
©
2013 HeteroCorporation

7
28
A. Babulreddy, R. V. Hymavathi, M. Hussain, and G. Narayana Swamy
Vol 50
(
15 mL) was added drop-wise during 20 min. Stirring was
regiocontrolled approach for the synthesis of this new class of
isoxazole-based bis-heterocycles.
continued for about 24 h. The separated solid was filtered and
recrystallized from 95% ethanol to furnish (2) at a yield of 86%.
To this intermediate (4 g, 0.017 mol) in ethanol (30 mL),
thiourea (2 g, 0.026 mol) was added and refluxed for 8 h, and
the reaction progress was monitored by TLC. The solvent was
evaporated under reduced pressure, and the solid was
recrystallized from 95% ethanol to obtain sharp crystals of (3)
(79%). To a solution of (3) (2 g, 0.0069 mol) in dry toluene
RESULTS AND DISCUSSION
Bromination of the ketone 1 followed by condensation
with thiourea in ethanol or methanol gave rise to the 4,5-
diaryl-2-amino-thiazole derivatives 3. Reaction of 3 with
propargyl bromide at room temperature under dry and inert
conditions in the presence of potassium carbonate afforded
the corresponding N-substituted propargyl amines 4.
Further reaction of 4 with different nitrile oxides 5 using
(
10 mL), a cooled solution of propargyl bromide (0.99 g,
0
2
.0083 mol) was added drop-wise in the presence of K CO3
(
1.15 g, 0.0083 mol) under nitrogen atmosphere. The reaction
ꢀ
mixture was refluxed on water bath at 110 C for 8 h, and the
reaction progress was monitored by TLC. The toluene and
propargyl bromide were removed by distillation, and the residue
was washed with sodium bicarbonate (5% w/v) followed by
cold water. The crude product was dried and recrystallized from
95% ethanol to obtain crystals of (4) (89%).
CuSO .5H O–sodiumascorbate system in a 2:1 mixture of
4
2
water and tert-butyl alcohol led to the formation of 6a–l in
good yields. The reactions were monitored by thin layer
chromatography (TLC; EOAc : hexane, 1:4). The chemical
structures of 6a–l were confirmed by elemental analysis
To a well-stirred solution of 4 (1 g, 0.003 mol), in 5 mL of
tertiary butanol and water mixture (2:1), copper sulfate
1
13
and spectral data (IR, H, C NMR, and mass spectra).
(
1
0.004 mol) and sodium ascorbate (0.28 mol) were added. After
5 min, aromatic nitrile oxides (5) (0.055 mmol) was added to
Characteristic IR absorption bands were observed for C–N,
N–O, C═N, C–S, and NH at 1037–1089, 1415–1477,
the aforementioned reaction mixture and stirred for 17–34 h.
The reaction progress was monitored by TLC. The resulting
mixture was diluted with water and extracted with ethyl acetate
(2 Â 20 mL). The organic layer was dried over anhydrous sodium
sulfate and evaporated under reduced pressure to afford a crude
product that upon recrystallization using EtOAc/hexane (1:4)
yielded title compounds 6a–l.
À1
1
518–1547, 719–774, and 3342–3392 cm , respectively [29].
The aromatic hydrogens resonated as multiplets at d 7.02–8.05.
Under the optimized conditions, a variety of substituents,
aromatic compounds, were readily used in this transformation.
Both electron-rich and electron-poor aromatic groups were
tolerated in 1,3-dipolar cycloaddition reaction. Generally, the
reaction was highly dependent on both electronic and steric
effects. An evident steric effect was observed when we com-
pared the yield of simple nitrile oxides with that of substituted
nitrile oxides (entries 1–12). On whole, the better yields were
obtained with simple nitrile oxides in a short period (entry 1).
But interestingly, aromatic nitrile oxides bearing electron-
[
4-(4-Chlorophenyl)-5-phenyl-thiazol-2-yl]-(3-phenyl-isoxazol-
À1
5
2
ylmethyl)-amine (6a). Semi solid; IR n (cm ): 3360, 3032,
983, 2852, 2365, 2342, 1632, 1537, 1467, 1330, 1269, 1121,
1
949, 851, 728; H NMR (400 MHz, CDCl ): d 7.19–7.81
(m, 14H), 6.84 (s, 1H), 4.72 (s, 2H), 4.06 (br s, 1H); C NMR
3
13
(
75 MHz, CDCl ) 173.19, 162.91, 155.23, 152.00, 148.71,
3
1
1
4
7
9
47.32, 136.91, 133.83, 131.35, 129.80, 129.31, 129.01, 128.59,
+
28.00, 127.03, 103.23, 106.06, 53.81; MS (EI) m/z: (M + 1)
withdrawing substituent, such as Cl, F, and NO group at
2
3
44; Anal. Calcd. for C25H18ClN OS: C, 67.64; H, 4.09; Cl,
.99; N, 9.47; S, 7.22. Found: C, 67.71; H, 4.03; Cl, 7.91; N,
.56; S, 7.28.
p-position afforded the product in prolonged period (6f, 6i,
and 6j; Table 1). The formation of 3,5-disubstituted isoxa-
zole has been unequivocally established through the charac-
teristic chemical shift value of the isoxazole proton 4-CH at d
[4-(4-Chlorophenyl)-5-phenyl-thiazol-2-yl]-(3-p-tolyl-isoxazol-
À1
5
2
ylmethyl)-amine (6b). Oil; IR n (cm ): 3278, 3132, 2923, 2853,
1
337, 1736, 1672, 1531, 1333, 1268, 1023, 844, 778, 672; H
6
7
.90–7.05 in contrast to the appearance of 3-Ch signal at d
.50–7.75 in the case of 4,5-disubstituted isoxazoles [29]
NMR (400 MHz, CDCl ): d 7.02–7.84 (m, 13H), 6.92 (s, 1H),
3
13
4
.68 (s, 2H), 4.09 (br s, 1H), 2.37 (s, 3H); C NMR (75MHz,
CDCl ) 175.03, 164.95, 161.09, 155.28, 152.30, 147.11, 146.72,
138.11, 133.71, 130.35, 129.80, 129.54, 129.36, 128.59, 128.07,
3
EXPERIMENTAL
+
1
27.93, 104.83, 53.43, 21.96; MS (EI) m/z: (M + 1) 458; Anal.
Column chromatography was carried out on silica gel. All
Calcd. for C H ClN OS: C, 68.19; H, 4.40; Cl, 7.74; N, 9.18;
26
20
3
melting points were determined in open capillary tubes on Mel-Temp
apparatus (Laboratory Devices, Cambridge, MA, USA) and are
S, 7.00. Found: C, 68.22; H, 4.39; Cl, 7.71; N, 9.25; S, 7.08.
[
4-(4-Chlorophenyl)-5-phenyl-thiazol-2-yl]-(3-o-tolyl-isoxazol-
À1
À1
uncorrected. Infrared spectra (υmax in cm ) were recorded as KBr
5
1
ylmethyl)-amine (6c). Oil; IR n (cm ): 3287, 3136, 2923, 2365,
677, 1534, 1476, 1349, 1276, 1175, 848, 779; H NMR
1
1
pellets on a Perkin-Elmer 283 double-beam spectrophotometer. H and
1
3
C NMR spectra were recorded on ABX 400 MHz spectrophotometer
(
(
400MHz, CDCL ): d 7.12–7.91 (m, 13H), 6.98 (s, 1H), 4.69
s, 2H), 4.14 (br s, 1H), 2.42 (s, 3H); C NMR (75MHz,
3
1
13
operating at 400 MHz for H NMR, and 75 MHz for C NMR
using CDCl as solvent. The H and C NMR chemical shifts were
13
1
13
3
3
CDCl ) 175.13, 165.01, 161.29, 155.23, 151.99, 148.12, 146.77,
referenced to tetra methyl silane (TMS).
Typical experimental procedure
1
1
38.12, 133.78, 130.31, 128.99, 129.44, 128.97, 128.19, 128.01,
27.93, 105.83, 53.42, 21.98; MS (EI) m/z: (M + 1) 458; Anal.
+
[
4-(4-Substituted phenyl)-5-(4-substituted phenyl)-thiazol-2-
Calcd. for C H ClN OS: C, 68.19; H, 4.40; Cl, 7.74; N, 9.18;
26 20 3
yl]-(3-substituted phenyl isoxazole-5-ylmethyl)-amine 6a–l. To
a well-stirred solution of ketone 1 (8 g, 0.035 mol) in acetic acid
S, 7.00. Found: C, 68.29; H, 4.38; Cl, 7.74; N, 9.24; S, 7.18.
[4-(4-Chlorophenyl)-5-phenyl-thiazol-2-yl]-(3-m-tolyl-isoxazol-
À1
(
70 mL), a solution of bromine (5.57 g, 0.035 mol) in acetic acid
5ylmethyl)-amine (6d). Oil; IR n (cm ): 3285, 3134, 2925, 2361,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2013
Synthesis, Characterization, and In Vitro Antimicrobial Activity of Methyleneamine-Linked
729
Bis-heterocycles
Table 1
Synthesis of isoxazole-based and thiazole-based novel unsymmetrical bis-heterocycles.
b
Reaction yield
a
Entry
1
N-substituted propargylamine
Nitrile oxide
Bis-heterocycle
Time (h)
17
%
94
2
3
4
5
25
28
22
25
91
86
79
91
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

7
30
A. Babulreddy, R. V. Hymavathi, M. Hussain, and G. Narayana Swamy
Vol 50
Table 1
Continued)
(
b
Reaction yield
a
Entry
6
N-substituted propargylamine
Nitrile oxide
Bis-heterocycle
Time (h)
31
%
87
7
27
84
8
22
79
9
32
34
29
83
82
81
10
11
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2013
Synthesis, Characterization, and In Vitro Antimicrobial Activity of Methyleneamine-Linked
731
Bis-heterocycles
Table 1
Continued)
(
b
Reaction yield
a
Entry
N-substituted propargylamine
Nitrile oxide
Bis-heterocycle
Time (h) %
12
22
79
a
1
13
All products were characterized by IR, H NMR, C NMR, and mass spectrometry.
b
Yields obtained after column chromatography.
1
1
(
(
678, 1536, 1473, 1344, 1276, 1178, 846, 774; H NMR
400 MHz, CDCl ): d 7.15–7.92 (m, 13H), 6.99 (s, 1H), 4.70
s, 2H), 4.16 (br s, 1H), 2.34 (s, 3H); C NMR (75 MHz,
[4-(4-Chlorophenyl)-5-phenyl-thiazol-2-yl]-[3-(3-chlorophenyl)-
isoxazol-5ylmethyl]-amine (6h). Semi solid; IR n (cm ): 3352
À1
3
13
3094, 2926, 2858, 2334, 1773, 1589, 1448, 1342, 1259, 1115,
1
CDCl ) 175.15, 164.91, 161.22, 155.24, 151.95, 148.92, 146.70,
38.16, 133.88, 130.91, 128.09, 129.45, 128.97, 128.19, 128.01,
27.93, 105.83, 53.42, 20.99; MS (EI) m/z: (M + 1) 458; Anal.
1025, 872, 751, 673; H NMR (400 MHz, CDCl ): d 7.12–7.90
3
3
13
1
1
(m, 13H), 7.00 (s, 1H), 4.72 (s, 2H), 4.18 (br s, 1H): C NMR
+
(75 MHz, CDCl ) 175.13, 163.47, 161.49, 158.07, 155.49, 153.29,
3
Calcd. for C H ClN OS: C, 68.15; H, 4.40; Cl, 7.74; N, 9.18;
146.99, 137.97, 135.29, 133.45, 132. 55, 129.88, 129.54, 129.31,
26
20
3
S, 7.00. Found: C, 68.31; H, 4.15; Cl, 7.71; N, 9.26; S, 7.12.
127.19, 126.08, 119.06, 108.95, 102.82, 55.41, 52.82; MS (EI) m/z:
+
[
4-(4-Chlorophenyl)-5-phenyl-thiazol-2-yl]-[3-(4-methoxyphenyl)-
(M + 1) 478; Anal. Calcd. for C H Cl N OS: C, 62.77; H, 3.58;
25
17
2 3
À1
isoxazol-5ylmethyl]-amine (6e). Oil; IR n (cm ): 3348, 3072,
Cl, 14.82; N, 8.78; S, 6.70. Found: C, 62.77; H, 3.51; Cl, 14.90; N,
8.87; S, 6.62.
1
2
994, 2360, 1654, 1578, 1438, 1367, 1281, 1105, 876, 745; H
NMR (400MHz, CDCl ): d 6.98–7.83 (m, 13H), 6.84 (s, 1H),
[4-(4-Chlorophenyl)-5-phenyl-thiazol-2-yl]-[3-(4-fluorophenyl)-
3
13
ꢀ
4
.76 (s, 2H), 4.11 (br s, 1H), 3.49 (s, 3H): C NMR (75 MHz,
CDCl ) 176.19, 163.63, 161.56, 158.26, 155.03, 153.36, 146.78,
38.56, 135.74, 133.46, 132. 05, 129.87, 129.49, 129.01, 128.42,
28.00, 119.67, 108.43, 101.73, 56.82, 53.81; MS (EI) m/z:
isoxazol-5ylmethyl]-amine (6i). Yellow solid; mp 212–213 C; IR n
À1
3
(cm ): 3342 3044, 2936, 2872,1602, 1534, 1458, 1386, 1280,
1
1
1
1175, 1031, 816, 757, 678; H NMR (400 MHz, CDCl3):
d 7.14–7.97 (m, 13H), 6.99 (s, 1H), 4.67 (s, 2H), 4.08 (br s,
+
13
(M + 1) 474; Anal. Calcd. for C26
3 2
H20ClN O S: C, 65.88; H,
3
1H); C NMR (75 MHz, CDCl ) 176.00, 163.09, 161.40,
4
7
.25; Cl, 7.48; N, 8.87; S, 6.77. Found: C, 67.93; H, 4.23; Cl,
.42; N, 8.82; S, 6.82.
159.00, 155.45, 153.76, 147.91, 138.97, 136.24, 134.66,
132.15, 129.97, 129.81, 129.23, 128.19, 126.43, 119.14,
108.86, 103.86, 55.28, 53.87; MS (EI) m/z: (M + 1) 462;
+
[
4-(4-Chlorophenyl)-5-phenyl-thiazol-2-yl]-[3-(4-chlorophenyl)-
ꢀ
isoxazol-5ylmethyl]-amine (6f). Solid; mp 196–197.5 C; IR n
Anal. Calcd. for C H ClFN OS: C, 65.00; H, 3.71; Cl, 7.67;
2
5
17
3
À1
(cm ): 3342 3072, 2923, 2853, 2337, 1771, 1598, 1457, 1343,
F, 4.11; N, 9.10; S, 6.94. Found: C, 65.13; H, 3.78; Cl, 7.87;
F, 4.16; N, 9.23; S, 6.88.
1
3
1258, 1105, 1021, 876, 750, 672; H NMR (400 MHz, CDCl ): d
7
.14–7.97 (m, 13H), 6.92 (s, 1H), 4.68 (s, 2H), 4.10 (br s, 1H);
[4-(4-Chlorophenyl)-5-phenyl-thiazol-2-yl]-[3-(4-nitrophenyl)-
1
3
À1
C NMR (75 MHz, CDCl ) 175.19, 163.45, 161.41, 158.00,
isoxazol-5ylmethyl]-amine (6j). Oil; IR n (cm ): 3342, 2936,
3
1
1
5
55.43, 153.27, 146.91, 137.97, 135.24, 133.46, 132. 05, 129.87,
2853, 2361, 1764, 1599, 1532, 1458, 1402, 1343, 1258, 1125,
1
29.49, 129.21, 127.09, 126.03, 119.04, 108.93, 102.86, 55.22,
1021, 858, 801, 750, 672; H NMR (400 MHz, CDCL
3
): d 7.21–
+
13
2.81; MS (EI) m/z: (M +1) 478; Anal. Calcd. for
7.96 (m, 13H), 7.01 (s, 1H), 4.72 (s, 2H), 4.14 (br s, 1H);
C
C H Cl N OS: C, 62.77; H, 3.58; Cl, 14.82; N, 8.78; S, 6.70.
NMR (75MHz, CDCl ) 176.01, 163.19, 162.45, 159.06, 154.45,
3
25
17
2 3
Found: C, 62.93; H, 3.34; Cl, 14.92; N, 8.82; S, 6.82.
153.71, 147.67, 137.92, 136.24, 133.76, 132.25, 129.91, 129.81,
[
4-(4-Chlorophenyl)-5-phenyl-thiazol-2-yl]-[3-(2-chlorophenyl)-
129.23, 128.19, 126.43, 119.14, 109.86, 104.86, 54.84, 52.87;
+
ꢀ
isoxazol-5ylmethyl]-amine (6g). Solid; mp 142–144 C; IR n
cm ): 3345 3074, 2927, 2856, 2338, 1775, 1594, 1456, 1345,
257, 1109, 1023, 875, 757, 674; H NMR (400 MHz, CDCl ): d
MS (EI) m/z: (M +1) 489; Anal. Calcd. for C25H17ClN O S: C,
4 3
À1
(
1
61.41; H, 3.50; Cl, 7.27; N, 11.46; S, 6.56. Found: C, 61.48; H,
3.58; Cl, 7.24; N, 11.53; S, 6.81.
1
3
7
.11–7.95 (m, 13H), 6.98 (s, 1H), 4.71 (s, 2H), 4.15 (br s, 1H);
[4-(4-Chlorophenyl)-5-phenyl-thiazol-2-yl]-(3-(2-nitrophenyl)-
isoxazol-5ylmethyl)-amine (6k). Oil; IR n (cm ): 3392, 3063,
1
3
À1
3
C NMR (75 MHz, CDCl ) 175.18, 163.55, 161.47, 158.01,
1
1
5
55.51, 153.17, 146.95, 137.98, 135.23, 133.46, 132. 05, 129.87,
2963, 2857, 2360, 1602, 1517, 1438, 1363, 1280, 1122, 1030,
1
29.49, 129.25, 127.19, 126.08, 119.14, 108.92, 102.14, 55.54,
841, 738, 644; H NMR (400 MHz, CDCl
3
): d 7.02–7.79
+
13
2.83; MS (EI) m/z: (M +1) 478; Anal. Calcd. for
(m, 14H), 6.89 (s, 1H), 4.78 (s, 2H), 4.11 (br s, 1H); C NMR
C H Cl N OS: C, 62.77; H, 3.58; Cl, 14.82; N, 8.78; S, 6.70.
(75 MHz, CDCl ) 172.99, 163.65, 154.23, 153.60, 148.73,
25
17
2
3
3
Found: C, 62.82; H, 3.58; Cl, 14.76; N, 8.88; S, 6.71.
147.82, 135.82, 134.81, 131.35, 129.84, 129.39, 129.00, 128.69,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

7
32
A. Babulreddy, R. V. Hymavathi, M. Hussain, and G. Narayana Swamy
Vol 50
Table 2
Antibacterial activity (minimum inhibition concentration; MIC) of 6a–l.
À1
Antibacterial activity (MIC, mg mL
)
Compound
P. aeruginosa
S. aureus
E. coli
S. faecalis
P. acnes
6
a
b
c
d
e
f
85
75
55
75
20
10
14
20
—
50
50
55
12
90
75
40
50
20
15
14
18
50
50
—
25
12
85
75
38
55
18
15
14
20
80
—
80
40
12
80
75
75
80
20
15
15
20
75
25
90
90
12
90
75
75
40
23
10
14
20
75
25
75
80
12
6
6
6
6
6
6
6
6
6
6
6
g
h
i
j
k
l
Ciprofloxacin
1
28.11, 127.03, 103.23, 106.06, 53.81, 51.04; MS (EI) m/z:
dilution method [30]. DMF was used as a blank and ciprofloxacin
as standard, and the results are presented in Table 2.
+
(M + 1) 489; Anal. Calcd. for C25
4 3
H17ClN O S: C, 61.41; H,
3
7
.50; Cl, 7.27; N, 11.46; S, 6.56. Found: C, 61.45; H, 3.54; Cl,
.28; N, 11.52; S, 6.76
An examination of the data reveals that all the compounds
À1
showed antibacterial activity ranging from 20 to 90 mg mL
.
[
4-(4-Chlorophenyl)-5-phenyl-thiazol-2-yl]-(3-(3-nitrophenyl)-
The compounds 6e–h were highly active against all the five
organisms employed. Compound 6l was highly active against P.
aeruginosa, E. coli, and S. aureus and the compound 6j against
E. coli, P. acnes, and S. faecalis. The results clearly indicate that
the presence of methoxy/chloro group at the phenyl ring increases
the antibacterial activity. The activity, however, was the maxi-
mum for a compound with two chloro groups.
À1
isoxazol-5ylmethyl)-amine (6l). Oil; IR n (cm ): 3402, 3069,
2
8
974, 2847, 2351, 1612, 1527, 1439, 1391, 1284, 1126, 1038,
1
43, 743, 649; H NMR (400 MHz, CDCl ): d 7.00–7.79
3
13
(
m, 13H), 6.89 (s, 1H), 4.65 (s, 2H), 4.03 (br s, 1H); C NMR
(
75 MHz, CDCl ) 174.39, 164.81, 161.23, 155.87, 151.93,
3
1
1
47.76, 146.37, 138.91, 134.93, 129.99, 129.82, 129.64, 129.26,
28.79, 128.27, 127.43, 104.93, 53.13, 22.01; MS (EI) m/z:
+
Antifungal activity. The compounds 6a–l were screened also
for their antifungal activity (Table 3) against Candida albicans
and Aspergillus niger using fungicide clotrimazole in DMF as
the standard [31]. All the compounds exhibited moderate to
high antifungal activity when compared with that of the
reference compound. Most of the compounds exerted high
activity against the tested fungi.
(
M + 1) 489; Anal. Calcd. for C H ClN O S: C, 61.41; H,
2
5
17
4 3
3
7
.50; Cl, 7.27; N, 11.46; S, 6.56. Found: C, 61.41; H, 3.49; Cl,
.16; N, 11.38; S, 6.42.
Antibacterial activity. The compounds 6a–l were screened for
their antibacterial activity against human pathogenic bacteria such as
Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli,
Streptococcus faecalis, and Propionibacterium acnes. The
minimum inhibition concentration was determined using the tube
Acknowledgment. The authors are thankful to the University
Grant Commission, New Delhi for financial help.
Table 3
Antifungal activity of 6a–l.
Zone of inhibition (in mm)
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