2
378 Singh et al.
Asian J. Chem.
-
1
by 2 mL of pyridine, the mixture was kept on ice bath and
then cold 2 mL of acetyl chloride was added in mixture. Conc.
Cl 16.60 (16.52), O 29.40 (29.81).FTIR(KBr, νmax, cm ): 3236
(C-H str. arom. ring), 3300 (O-H str.), 1454 (C=C str. arom.
ring), 1300 (C-C str.), 1233 (C-H bend.), 890 (O-H bend.),
800-500 (=C-H bend.). MS: m/z 214.00 (100.0 %), 216.00
(32.0 %), 215.01 (10.0 %), 217.00 (3.2 %), 216.01 (1.3 %).
Synthesis of 5-chloro-2-(1H-indol-2-yl)benzoic acid (3b):
In this method, 5-chloro-2-(1H-indol-2-yl)benzoic acid (3b)
was prepared by Shaikh et al. method [18]. The mixture of
compound 2b (0.01 mol), phenylhydrazene (0.01 mol) and
12 mL of ethanol was refluxed for 2-3 h at 25-30 ºC, cooled at
H
2
SO (0.1 mL) was added and the mixture was stirred and poured
4
into 15 mL of distilled water. The reaction mixture was heated
at 60 ºC till dissolution then kept on ice bath till crystals were
formed. The crystals were filtered, washed with cold water and
recrystallized with ethanol to get fine crystals of 2-acetoxy-
benzoic acid (2a). Yield: 59.23 % (180 g), m.w. C
50 ºC, R : 0.5. Elemental analysis calcd. (found) (%): C 60.00
60.00); H 4.46 (4.48), O 35.54 (35.52). FTIR (KBr, νmax, cm ):
238 =C-H str. arom. ring) , 3100-2500 (OH str. COOH), 1658
C=O str. COCH ), 1612 (C=O str. COOH), 1483 (C=C str. arom.
9 8 4
H O , m.p.
1
(
f
-1
3
room temperature and poured into 8 mL conc. H
2
SO . The
4
(
3
reaction mixture was then heated, stirred for 20-30 min and
then poured into 20 mL of ice cold water to get solid product.
The crystals were filtered, dried and recrystallized with methanol.
NCl, m.p. 170 ºC, R :
0.82. Elemental analysis calcd. (found) (%): C 66.80 (66.30);
H 4.60 (3.71), N 5.90 (5.16), Cl 11.35 (13.0), O 11.35 (11.78).
FTIR(KBr, νmax, cm ): 3449 (NH str. -NH=N-) 2607, 2488, 2360
(Ar overtones), 2889 (C-H str. arom. ring), 1604 (C=C str. arom.
ring), 688, 742 (C-H bend. arom. bend.). MS: m/z 210.12 (100.0
%), 211.12 (15.1 %), 212.12 (1.1 %).
ring), 1440 (C-H bend. arom. ring), 1296 (OH bend. carbonyl ).
MS: m/z 180.04 (100.0 %), 181.05 (10.0 %), 182.05 (1.3 %).
Synthesis of 2-(1H-indol-2-yl)benzoic acid (3a): In this
method, 2-(1H-indol-2-yl)benzoic acid (3a) was prepared by
Shaikh et al. method [18]. The mixture of compound 2a (0.01
mol) and phenylhydrazene (0.01 mol) and 12 mL of ethanol
was taken in round bottom flask. The reaction mixture was reflu-
xed for 2-3 h at 25-30 ºC, cooled at room temperature and poured
Yield: 50.00 % (272.5 g), m.w. C15
H
11
O
2
f
-1
into 8 mL conc. H
2
SO . The mixture was then heated and stirred
4
for 20-30 min and poured into 20 mL of ice cold water to get
solid product. The crystals were filtered, dried and recrystall-
Molecular docking study: The molecular docking calcu-
lations was carried out usingArgusLab software. The molecular
docking studies revealed that ligand of respective synthesized
compounds 2a-b and 3a-b had been found docked successfully
with H-bonding on the binding site (amino acids) of 3JUS (Figs.
1-4) and 3UPI protein (Figs. 5-8), selected from pdb. The best
ligand pose energies had been quite remarkable in case of 3JUS
as listed in Table-1. The best ligand pose energies had also
been quite remarkable in case of 3UPI (Table-2).
ized with methanol. Yield: 38.81 % (273 g), m.w. C15
m.p. 170 ºC, R : 0.9. Elemental analysis calcd. (found) (%): C
5.80 (75.90); H 4.60 (4.60), N 5.90 (5.90), O 13.35 (13.40).
H
11
2
O N,
f
7
-1
FTIR(KBr, νmax, cm ): 3438 (NH str. -NH=N-) 2607, 2488, 2360
Ar overtones), 2889 (C-H str. arom. ring), 1604 (C=C str. arom.
ring), 688, 742 (C-H bend. arom. bend.). MS: m/z 210.12 (100.0
(
%
), 211.12 (15.1 %), 212.12 (1.1 %).
Synthesis of 5-chloro-2-acetoxybenzoic acid (2b): 5-
RESULTS AND DISCUSSION
Chloro-2-hydroxybenzoic (0.02 mol), 2 mL of pyridine and 4
mL of toluene were heated till dissolution in 100 mL beaker.
Then 2 mL of cold acetyl chloride was added followed by the
The interesting outcome of this work is the synthesis of
indoles through salicylic acid followed by cyclization (Scheme-I).
Though, low yield has been a matter of concern. As shown in
the highlighted case studies, molecular docking has been able
to identify promising compounds that might represent future
solutions in critical areas of human health. The compounds,
2-(1H-indol-2-yl)benzoic acid (3a) and 5-chloro-2-(1H-indol-
2-yl)benzoic acid (3b) showed promising activity of varying
degree. The compound 3a had been found docked with binding
amino acids such as 752 GLY:coil, 580 THR:alpha helix etc.
addition of 0.1 mL of conc. H
2
SO . The reaction mixture was
4
stirred and poured into 15 mL of distilled water. It was then
heated at 60 ºC till dissolution got completed and mixture was
kept on ice bath to get crystals. The crystals were filtered, washed
and dried. The recrystallization with ethanol yielded pure
crystals of 5-chloro-2-acetoxybenzoic acid (2b). Yield: 95.60
%
(214.5 g), m.w. C
H
9 7
4
O Cl, m.p. 80 ºC, R
f
: 0.9. Elemental
analysis calcd. (found) (%): C 50.48 (50.38), H 3.53 (3.29),
Fig. 1. Molecular docking of colour ribbon as chain position and render protein as cartoon ribbon for compound 2a with 3JUS