Month 2018
Design, Synthesis and Computational studies of novel Carbazole N-phenylacetamide
hybrids as potent Anti-bacterial, Anti-inflammatory and Antioxidant agents
tested compounds, 3a, 3e, 3g, 3h, and 3i exhibited
antibacterial activity with MICs ranging from 2.0 to
109.9, 110.0, 114.9, 119.8, 120.1, 120.8, 124.4, 125.1, 126.0,
1
M
26.7, 128.6, 134.4, 137.4, 138.9, 140.6, 170.2, 175.4, EI-MS:
+
·
2 2 3
m/z 455; Anal. Calcd for C24H20Cl N O (%), Calcd: C,
0.25 μg/mL. Compounds 3a, 3b, 3g, and 3i showed
6
3.31; H, 4.43; N, 6.15; found: C, 63.30; H, 4.41; N, 6.14;
excellent anti-inflammatory activity. Compound 3f
showed excellent antioxidant activity and remaining
derivatives have shown moderate activity. These results
will help succeeding generation in design and discovery
of potent antimicrobial drugs taking into account of
this work.
Methyl 2-(6-chloro-9-(2-(2-chlorophenylamino)-2-oxoethyl)-
9
H-carbazol-2-yl)propanoate (3c).
As light yellow powder,
ꢀ1
Yield 77%; m.p: 230–232°C; IR (KBr) cm 3416.25 (-NH)
1
1
677.29 (C¼O ester) and 1660.01 (C¼O amide); H-NMR
(400 MHz, CDCl , TMS) δ (ppm): 9.86 (s, 1H, -NH), 7.82–
.72 (m, 10H, Ar-H), 5.82 (s, 2H, -NCH ), 3.66 (q, 1H, C -H),
3
8
2
2
14
13
.72 (s, 3H, C -H ester), 1.56 (d, 3H, C -H); C-NMR
17
15
(
100 MHz, CDCl
3
) δ (ppm): 18.5, 45.1, 51.9, 57.2, 109.7,
1
1
1
12.5, 117.9, 119.5, 123.2, 123.4, 123.5, 123.9, 124.2, 124.9,
EXPERIMENTAL SECTION
25.4, 127.5, 128.9, 129.2, 131.3, 135.8, 137.7, 140.1, 169.5,
+
·
74.9, EI-MS: M m/z 455; Anal. Calcd for C H Cl N O
2 2 3
24
20
Chemistry.
Melting points were determined with open
capillary method on a Buchi apparatus and are uncorrected. IR
spectra were recorded on a Nicolet 5700 FT-IR instrument
(
%), Calcd: C, 63.31; H, 4.43; N, 6.15; found: C, 63.28; H,
4
.42; N, 6.13;
Methyl 2-(6-chloro-9-(2-(3-chlorophenylamino)-2-oxoethyl)-
1
13
(
Nicolet, Madison, WI, USA) as using KBr pellets. H and
NMR spectra were recorded on Bruker 400 MHz Spectrometer
using CDCl as solvent and TMS as an internal standard and
chemical shifts were reported as δ values (ppm). Mass spectra
were recorded using Shimadzu GCMSQP2010S. The elemental
analysis was carried out using Hereaus CHN rapid analyzer.
Purity of the compound was checked by TLC. All the chemicals
purchased were of analytical grade and were used without
further purification unless otherwise stated.
C
9H-carbazol-2-yl)propanoate (3d).
This compound is
obtained as buff color and Yield 87%; m.p: 215–217°C; IR
ꢀ1
3
(
(
8
KBr) cm 3417.36 (-NH) 1678.32 (C¼O ester) and 1659.26
1
C¼O amide); H-NMR (400 MHz, CDCl
3
, TMS) δ (ppm):
.72 (s, 1H, -NH), 7.50–8.43 (m, 10H, Ar-H), 5.52 (s, 2H, -
2
NCH ), 3.35 (q, 1H, C14-H), 2.42 (s, 3H, C17-H ester), 1.51 (d,
13
15 3
3
5
1
H, C -H); C-NMR (100 MHz, CDCl ) δ (ppm): 18.7, 45.7,
2.9, 55.2, 109.7, 112.5, 117.5, 117.9, 118.50, 119.50, 122.8,
23.2, 123.4, 123.5, 123.9, 125.4, 130.3, 133.0, 135.8, 137.7,
+
·
General procedure for the synthesis of title compounds.
The substituted methyl 2-(6-chloro-9-(2-oxo-2-(phenylamino)
ethyl)-9H-carbazol-2-yl)propanoate were synthesized by
condensation of substituted 2-chloro-N-phenylacetamide 1(a–c)
140.1, 140.1, 169.5, 174.9, EI-MS: M m/z 455; Anal. Calcd
for C H Cl N O (%), Calcd: C, 63.31; H, 4.43; N, 6.15;
found: C, 63.29; H, 4.41; N, 6.14;
24
20
2 2 3
Methyl 2-(9-(2-(4-bromophenylamino)-2-oxoethyl)-6-chloro-
(
3 to 5 equiv) with methyl 2-(6-chloro-9H-carbazol-2-yl)
9H-carbazol-2-yl)propanoate (3e).
powder, Yield 71%; m.p: 198–200°C; 3416.11 (-NH) 1688.37
As a light brown color
propanoate (2) (0.05 M) in anhydrous Cs CO (5 equiv) using
2
3
1
acetonitrile as the solvent [15]. The mixture was refluxed for
about 5 h. After completion of the reaction being cooled to
room temperature, the mixture was filtered. EtOAc and H
were added to the filtrate. After separation, the organic phase
(C¼O ester) and 1657.17 (C¼O amide); H-NMR (400 MHz,
CDCl , TMS) δ (ppm): 8.70 (s, 1H, -NH), 7.19–8.30 (m, 10H,
3
2
O
Ar-H), 5.94 (s, 2H, -NCH ), 3.75 (q, 1H, C -H), 2.53 (s, 3H,
C -H ester), 1.50 (d, 3H, C -H); C-NMR (100 MHz,
17 15
2
14
13
was dried over MgSO and concentrated in vacuo. The residue
was purified by column chromatography(Cy/EtOAc) to provide
the title compound.
CDCl ) δ (ppm): 18.5, 45.1, 51.9, 57.2, 109.7, 112.5, 115.2,
4
3
117.9, 119.5, 120.7, 123.2, 123.4, 123.5, 123.9, 125.4, 130.6,
+
·
135.8, 137.7, 138.4, 140.1, 169.5, 174.9, EI-MS: M m/z 499;
Anal. Calcd for C H BrClN O (%), Calcd: C, 57.68; H, 4.03;
Methyl
2-(6-chloro-9-(2-(4-methoxyphenylamino)-2-
24
20
2 3
oxoethyl)-9H-carbazol-2-yl)propanoate (3a). This compound
is obtained as a light green color and Yield 84%; m.p: 210–
N, 5.61; found: C, 57.66; H, 4.02; N, 5.60;
Methyl 2-(9-(2-(3-bromophenylamino)-2-oxoethyl)-6-chloro-
ꢀ
1
2
12°C; IR (KBr) cm 3418.29 (-NH) 1676.18 (C¼O ester)
9H-carbazol-2-yl)propanoate (3f).
As a brown color solid,
1
ꢀ1
and 1654.54 (C¼O amide); H-NMR (400 MHz, CDCl
δ (ppm): 8.30 (s, 1H, -NH), 7.15–7.35 (m, 10H, Ar-H), 4.46 (s,
H, -NCH ), 3.79 (q, 1H, C -H), 3.76 (s, 3H, C -OCH ), 3.69
3
, TMS)
Yield 80%; m.p: 220–222°C; IR (KBr) cm 3419.12 (-NH)
1
1681.52 (C¼O ester) and 1659.31 (C¼O amide); H-NMR
2
(400 MHz, CDCl , TMS) δ (ppm): 8.62 (s, 1H, -NH), 7.19–
2
15
4
3
3
1
3
(s, 3H, C -H ester), 1.56 (d, 3H, C -H); C-NMR (100 MHz,
8.30 (m, 10H, Ar-H), 5.90 (s, 2H, -NCH ), 3.62 (q, 1H, C -H),
1
8
16
2
14
13
CDCl
3
) δ (ppm): 18.7, 31.0, 45.6, 53.81, 55.5, 109.8, 111.7,
2.58 (s, 3H, C -H ester), 1.51 (d, 3H, C -H); C-NMR
17 15
1
1
4
5
14.8, 119.6, 120.0, 120.6, 124.2, 124.9, 125.9, 126.6, 128.4,
(100 MHz, CDCl ) δ (ppm): 18.5, 45.1, 51.9, 57.2, 109.7,
112.5, 117.9, 118.1, 119.5, 121.6, 122.05, 123.2, 123.4, 123.5,
3
+
·
34.2, 137.3, 137.4, 140.4, 156.6, 172.8, 178.5,EI-MS: M m/z
50; Anal. Calcd for C H ClN O (%), Calcd: C, 66.59; H,
2
5
23
2
4
123.9, 125.4, 126.0, 131.2, 135.8, 137.7, 140.1, 141.1, 169.5,
+
·
.14; N, 6.21; found: C, 66.58; H, 5.13; N, 6.19;
174.9, EI-MS: M m/z 499; Anal. Calcd for C H BrClN O
24 20 2 3
Methyl 2-(6-chloro-9-(2-(4-chlorophenylamino)-2-oxoethyl)-
(%), Calcd: C, 57.68; H, 4.03; N, 5.61; found: C, 57.67; H,
4.03; N, 5.60;
9
H-carbazol-2-yl)propanoate (3b).
Yield 87%; m.p: 221–225°C; IR (KBr) cm 3415.93 (-NH)
As buff color powder,
ꢀ
1
Methyl
2-(6-chloro-9-(2-(2,6-dimethylphenylamino)-2-
As a colorless
1
1
(
8
2
(
682.21 (C¼O ester) and 1659.33 (C¼O amide); H-NMR
oxoethyl)-9H-carbazol-2-yl)propanoate (3g).
powder, Yield 69%; m.p: 247–249°C; IR (KBr) cm 3416.23
ꢀ
1
400 MHz, CDCl , TMS) δ (ppm): 9.06 (s, 1H, -NH), 7.77–
3
1
.61 (m, 10H, Ar-H), 5.75 (s, 2H, -NCH ), 3.59 (q, 1H, C -H),
(-NH) 1677.35 (C¼O ester) and 1650.48 (C¼O amide); H-
2
14
1
3
.66 (s, 3H, C17-H ester), 1.50 (d, 3H, C15-H); C-NMR
) δ (ppm): 18.8, 45.7, 53.9, 55.7, 107.1,
3
NMR (400 MHz, CDCl , TMS) δ (ppm): 9.43 (s, 1H, -NH),
100 MHz, CDCl
3
2
7.02–7.24 (m, 9H, Ar-H), 5.81 (s, 2H, -NCH ), 4.37 (q, 1H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet