Iodine-catalyzed conjugate addition of indoles onto en-1,4-dione: A novel synthesis of 3-(1-(1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-ones as antibacterial and antifungal agents

Article abstract of DOI:10.1016/j.bmcl.2011.08.075

Indole and its derivatives undergo smooth conjugate addition onto en-1,4-dione derived from isatin and acetophenone, in the presence of a catalytic amount of molecular iodine in acetonitrile under mild conditions to afford a novel class of 3-(1-(1H-indol-

Full text of DOI:10.1016/j.bmcl.2011.08.075

Bioorganic & Medicinal Chemistry Letters 21 (2011) 6510–6514
Contents lists available at SciVerse ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Iodine-catalyzed conjugate addition of indoles onto en-1,4-dione: A novel
synthesis of 3-(1-(1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-ones
as antibacterial and antifungal agents
B.V. Subba Reddy a, , N. Rajeswari b, M. Sarangapani b, G. Roopa Reddy a, Ch. Madan a,
⇑
K. Pranay Kumar c, M. Srinivasa Rao c
a Organic Chemistry Division-1, Indian Institute of Chemical Technology, Hyderabad 500 007, India
b College of Pharmacy, Kakatiya University, Warangal, India
c Biology Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Indole and its derivatives undergo smooth conjugate addition onto en-1,4-dione derived from isatin and
acetophenone, in the presence of a catalytic amount of molecular iodine in acetonitrile under mild con-
ditions to afford a novel class of 3-(1-(1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-one derivatives in
good yields with high degree of 1,4-selectivity. Some of these compounds are found to exhibit modest
antibacterial and antifungal properties.
Received 22 November 2010
Revised 12 August 2011
Accepted 15 August 2011
Available online 22 August 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
en-1,4-Dione
Indoles
Molecular iodine
Antifungal
Antimicrobial activity
Indoles and its derivatives are found abundantly in nature and
are known to exhibit potent physiological properties.1 Therefore,
the synthesis and reactions of indoles have attracted great promi-
nence in organic synthesis.2,3 Substituted Indoles are capable of
binding to many receptors with high affinity. In particular, 3-substi-
tuted indoles are important building blocks for the synthesis of
many biologically active natural products.4 As a result, there is a
growing interest in the development of improved methods for the
synthesis of 3-substituted indoles.5 Among various transforma-
tions, Lewis acid catalyzed C–C bond forming reactions are of great
importance in Organic synthesis because of their high reactivity,
selectivity, and mild reaction conditions.6 Recently, molecular io-
dine has received considerable attention in organic synthesis
because of its high tolerance to air and moisture, low-cost, nontoxic
nature, and ready availability, affording the corresponding products
in excellent yields. The mild Lewis acidity associated with iodine
has led to its use in organic synthesis using catalytic to stoichiom-
etric amounts.7
H
N
O
O
O
O
10 mol% I2
CH3CN, r.t.
+
N
H
1
N
H
N
H
3a
2
Scheme 1. Preparation of 3-(1-(1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-
one.
tone derived from isatin and acetophenone using molecular iodine
as a novel catalyst. As a preliminary experiment, en-1,4-dione
(1) was treated with indole (2) in the presence of 10 mol % of
molecular iodine. The reaction proceeded smoothly in acetonitrile
at room temperature and the corresponding Michael adduct 3a
was obtained in 78% yield (Scheme 1).
This result provided the incentive for further study of reactions
with various indoles. Interestingly, substituted indoles such as
5-cyano-, 2-methyl-5-nitro-, 1-methyl-, 5-bromo-, 5-nitro-,
methyl 5-carboxylate, 2-methyl-, 5-chloro-, and 2-phenyl deriva-
tives reacted well with en-1,4-diketone to furnish the respective
3-(1-(1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-one deriva-
In continuation of our interest on the use of molecular iodine for
various transformations,8 we herein report for the first time, a di-
rect and metal-free conjugate addition of indoles onto en-1,4-dike-
⇑
Corresponding author.
E-mail address: basireddy@iict.res.in (B.V.S. Reddy).
0960-894X/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2011.08.075

B.V.S. Reddy et al. / Bioorg. Med. Chem. Lett. 21 (2011) 6510–6514
6511
Table 1
Conjugate addition of indoles onto en-1,4-diketones
Entry
Isatin
Indole
Producta
Time (h)
Yield (%)b
NH
O
N
H
a
12
78
O
O
N
H
O
N
H
NC
NH
NC
N
H
b
15
85
O
O
O
O
N
H
O
O
O
N
O
H
O2N
NH
Me
O
O2N
Me
N
H
c
22
84
N
H
N
H
O
Me
N
N
Me
d
18
85
N
H
O
N
O
H
Br
NH
Br
N
H
e
18
20
14
18
90
75
82
O
O
O
O
O
O
O
N
H
N
O
H
O2N
NH
O2N
N
H
f
O
N
H
N
H
O
MeO2C
NH
MeO2C
N
H
g
O
O
O
N
H
N
H
O
NH
Me
N
Me
H
h
90
O
N
H
N
O
H
(continued on next page)

6512
B.V.S. Reddy et al. / Bioorg. Med. Chem. Lett. 21 (2011) 6510–6514
Table 1 (continued)
Entry
Isatin
Indole
Producta
Time (h)
Yield (%)b
Cl
NH
Cl
N
H
i
18
88
O
O
O
N
H
O
O
N
H
O
NH
Ph
N
H
Ph
j
20
80
O
N
H
N
O
H
a
The products were characterized by NMR, IR, and mass spectroscopy.
Yield refers to pure products after chromatography.
b
tives in excellent yields (Table 1, entries b–j). Notably, electron-
deficient indoles such as 5-cyano-, 2-methyl-5-nitro-, 5-nitro-,
and 5-methoxycarbonyl derivatives participated efficiently in this
reaction under similar conditions (Table 1, entries b, c, f, and g).
Furthermore, N-methylindole also gave the desired product in
85% yield (Table 1, entry d). This method works well with both
electron rich as well as electron deficient indoles. The products
were characterized and confirmed by NMR, IR, and mass spectros-
copy. In all the cases, the reactions proceeded well at room temper-
ature affording the corresponding 1,4-adducts in excellent yields
with high 1,4-selectivity (Table 1). However, in the absence of
iodine, no reaction was observed even under reflux conditions. This
clearly indicates that molecular iodine is essential to facilitate the
reaction. The scope and generality of this process is illustrated with
respect to various indoles and en-1,4-diketone and the results are
presented in Table 1.9 The salient features of this method are high
1,4-selectivity, excellent yields, mild reaction conditions and low
cost of the catalyst.
Mechanistically, we assume that the reaction proceeds by the
activation of en-1,4-dione by molecular iodine. Subsequent attack
of indole on activated double bond would give the 1,4-addition
product. Due to steric hindrance at C2 position of enone, indole
selectively at C3 position of enone to give the desired product as
depicted in Scheme 2.
Other alternative pathway is that HI being produced by interac-
tion of iodine with NH could also catalyze the reaction. However,
the reaction was not so effective when a solution of 10 mol % of
HI was used as a catalyst. No electrophilic iodination was observed
under the reaction conditions.10 The reaction though proceeds
with protic acids such as KSF clay, the desired products were ob-
tained in low yields compared to molecular iodine. The efficacy
of various Lewis acids such as BiCl3, ZrCl4 and BF3ÁOEt2 was also
tested for this conversion. However, the reactions are not clean
and formed a mixture of products with other Lewis acids.
The minimum inhibitory concentrations (MIC) of various
synthetic compounds were tested against three representative
Gram-positive organisms viz. Bacillus subtilis (MTCC 441), Staphylo-
coccus aureus (MTCC 96), Staphylococcus epidermidis and Gram-
negative organisms viz. Escherichia coli (MTCC 443), Pseudomonas
a
H
N
b
N
H
3
2
O
O
I2
O
O
I2
a
O
O
CH3CN
N
H
N
H
N
H
b
NH
O
O
N
H
Scheme 2. A plausible reaction mechanism.
Table 2
Antimicrobial activity of compounds
MIC (lg/ml)
Compd code
B. subtilis
S. aureus
S. epidermidis
E. coli
P. aeruginosa
K. pneumoniae
3a
3b
3c
3d
3e
3f
3g
3h
75
150
150
150
150
75
150
150
150
150
1.562
6.25
75
150
150
150
150
150
75
37.5
18.75
75
150
150
150
150
150
150
150
150
75
150
150
150
150
150
150
150
150
150
150
12.5
6.25
9.375
150
150
150
150
150
150
150
150
150
150
150
150
6.25
3.125
18.75
18.75
9.375
18.75
18.75
9.375
9.375
12.5
3i
3j
75
3.125
3.125
Penicillin
Streptomycin
1.562
6.25
1.562

B.V.S. Reddy et al. / Bioorg. Med. Chem. Lett. 21 (2011) 6510–6514
6513
Table 3
Antifungal activity of compounds
Zone of inhibition in MM
Compd code
C. albicans
C. rugosa
S. cerevisiae
A. flavus
100
lg
150
lg
100
lg
150
lg
100
l
g
150
lg
100
lg
150 lg
3a
3b
3c
3d
3e
3f
3g
3h
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
11
8
0
10
0
0
10
9
13
12
21
16
11
0
16
15
0
15
13
17
17
0
0
0
0
0
0
0
0
0
0
22
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
25
0
0
0
0
0
0
0
0
0
0
3i
3j
0
0
23.5
Amphotericin-B (50)
aeruginosa (MTCC 741), and Klebsiella pneumoniae (MTCC 618) by
broth dilution method recommended by National Committee for
Clinical Laboratory (NCCL) standards (1).11 Standard antibacterial
agents like Penicillin and Streptomycin were also screened under
identical conditions for comparison. The minimum inhibitory con-
centration (MIC) values are presented in Table 2.
one derivatives by means of a conjugate addition of indoles onto
en-1,4-dione using a catalytic amount of molecular iodine under
mild conditions. This method is simple and convenient to prepare
a wide range of indolinone derivatives which are found to possess
interesting antibacterial properties.
All synthesized compounds were tested for in vitro antimicro-
bial activity. The MIC values of the compounds against pathogenic
bacteria are presented in Table 2. The experimental results of anti-
microbial activity indicated a variable degree of efficacy of the
compounds against different strains of bacteria. Compounds 3a,
Acknowledgments
Ch.M. and G.R.R. thank J.S. Yadav, Director, IICT, for the financial
assistance.
3f, 3i, and 3j showed very strong activity (9.375
3d, 3e, 3g, 3h showed significant activity against P. aeruginosa
(18.75 g/ml). However, the compounds are effective against P.
aeruginosa only. They did not show any considerable effect on
other strains (75–150 g/ml) as indicated in Table 2. The substitu-
tion at 5th position on indole moiety with NO2, and Cl and phenyl
group at 2nd position and unsubstituted indole have shown more
activity, when compared to methyl substitutions at 1st and 2nd
positions.
In vitro antifungal activity of the newly synthesized compounds
was studied against the fungal strains such as Candida albicans
(MTCC 227), Saccharomyces cerevisiae (MTCC 36), Rhizopus oryzae
(MTCC 262), Aspergillus niger (MTCC 282) by Agar Well Diffusion
Method (2). Agar well bioassay was employed for testing anti-
fungal activity.12 The ready-made Potato Dextrose Agar (PDA)
medium (Hi-media, 39 g) was suspended in distilled water
(1000 mL) and heated to boiling until it dissolved completely, the
medium and Petri dishes were autoclaved at pressure of 15 lb/inc
for 20 min. The medium was poured into sterile Petri dishes under
aseptic conditions in a laminar air flow chamber.
When the medium in the plates was solidified, 0.5 mL of (week
old) culture of test organism was inoculated and uniformly spread
over the agar surface with a sterile L-shaped rod. Solutions were
prepared by dissolving the compound in DMSO and different con-
centrations were made. After inoculation, the wells were scooped
out with 6 mm sterile cork borer and the lids of the dishes were re-
placed. To each well different concentrations of test solutions were
added. Controls were maintained. The treated samples and the
controls were kept at 27 °C for 48 h. Inhibition zones were mea-
sured and the diameter was calculated in millimeter. Three to four
replicates were maintained for each treatment.
l
g/mL), whereas
References and notes
1. (a) Sundberg, R. J. Indoles; Academic Press: San Diego, 1996; (b) Faulkner, D. J.
Nat. Prod. Rep. 2001, 18, 1; (c) Ninomiya, I. J. Nat. Prod. 1992, 55, 541.
2. (a) Bandini, M.; Melloni, A.; Umani-Ronchi, A. Angew. Chem., Int. Ed. 2004, 43,
550; (b) Austin, J. F.; MacMillan, D. W. C. J. Am. Chem. Soc. 2002, 124, 1172; (c)
Jensen, K. B.; Thorhange, J.; Hazel, R. G.; Jorgensen, K. A. Angew. Chem., Int. Ed.
2001, 40, 160.
3. (a) Srivastava, N.; Banik, B. K. J. Org. Chem. 2003, 68, 2109; (b) Bartoli, G.;
Bartolacci, M.; Bosco, M.; Foglia, G.; Giuliani, A.; Marcantoni, E.; Sambri, L.;
Torregiani, E. J. Org. Chem. 2003, 68, 4594.
4. (a) Yoshiaki, N.; Masato, Y.; Youichi, I.; Masnobu, H.; Sakae, U. J. Am. Chem. Soc.
2002, 124, 11846; (b) Wenkert, E.; Angell, E. C.; Ferreira, V. F.; Michelotti, E. L.;
Piettre, S. R.; Sheu, J. H.; Swindell, C. S. J. Org. Chem. 1986, 51, 2343.
5. (a) Campos, K. R.; Woo, J. C. S.; Lee, S.; Tillyer, R. D. Org. Lett. 2004, 6, 79; (b)
Hong, K. B.; Lee, C. W.; Yum, E. K. Tetrahedron Lett. 2004, 45, 693; (c) Kohling, P.;
Schmidt, A. M.; Eilbracht, P. Org. Lett. 2003, 5, 3213; (d) Yadav, J. S.; Abraham,
S.; Reddy, B. V. S.; Sabitha, G. Synthesis 2001, 2165; (e) Arcadi, A.; Bianchi, G.;
Chiarini, M.; Anniballe, G.; Marinelli, F. Synlett 2004, 944.
l
l
6. Kobayashi, S. Eur. J. Org. Chem. 1999, 15.
7. (a) Togo, H.; Iida, S. Synlett 2006, 2159; (b) Lin, X.-F.; Cui, S.-L.; Wang, Y.-G.
Tetrahedron Lett. 2006, 47, 4509; (c) Chen, W.-Y.; Lu, J. Synlett 2005, 1337; (d)
Royer, L.; De, S. K.; Gibbs, R. A. Tetrahedron Lett. 2005, 46, 4595; (f) Wang, S.-Y.
Synlett 2004, 2642; (g) Ko, S.; Sastry, M. N. V.; Lin, C.; Yao, C.-F. Tetrahedron Lett.
2005, 46, 5771.
8. Yadav, J. S.; Reddy, B. V. S.; Hashim, S. R. J. Chem. Soc., Perkin Trans. 1 2000,
3082; (b) Yadav, J. S.; Reddy, B. V. S.; Premalatha, K.; Swamy, T. Tetrahedron Lett.
2005, 46, 2687; (c) Yadav, J. S.; Reddy, B. V. S.; Sabitha, G.; Reddy, G. S. K. K.
Synthesis 2000, 1532; (d) Yadav, J. S.; Reddy, B. V. S.; Rao, C. V.; Chand, P. K.;
Prasad, A. R. Synlett 2001, 1638; (e) Yadav, J. S.; Reddy, B. V. S.; Reddy, M. S.;
Prasad, A. R. Tetrahedron Lett. 2002, 43, 9703.
9. General procedure: To
a stirred solution of en-1,4-diketone (1 mmol) in
acetonitrile (4 mL) were added molecular iodine (25.3 mg, 10 mol %) followed
by indole (1 mmol) at room temperature. The resulting mixture was stirred at
room temperature for the appropriate time (Table 1). After complete
conversion, as indicated by TLC, the reaction mixture was quenched by
saturated sodium thiosulphate solution (4 mL) and extracted with
dichloromethane (3 Â 10 mL). The combined organic layers were dried over
anhydrous Na2SO4 and concentrated in vacuo and purified by column
chromatography on silica gel (Merck, 60–120 mesh, ethyl acetate/hexane,
3:7) to afford the pure 3-(1-(1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-
one. Spectral data for the selected products:
3-(1-(1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-one
(300 MHz, CDCl3 + DMSO, 1:4): 4.10 (d, 1H, J = 3.5 Hz), 5.72 (d, 1H,
J = 3.5 Hz), 6.30 (d, 1H, J = 7.7 Hz), 6.66–6.82 (m, 2H), 6.90–7.40 (m, 6H),
7.41–7.45 (m, 1H), 7.50 (s, 1H), 7.84 (d, 2H, J = 8.3 Hz), 8.04 (s, 1H), 10.12 (br s,
1H, NH), 10.80 (br s, 1H, NH); 13C NMR (75 MHz, CDCl3 + DMSO, 1:4): d 193.2,
175.4, 140.1138.3, 132.7, 130.5, 125.1, 124.2, 122.7, 122.5, 122.2, 121.1, 120.9,
The antifungal activity was started with pathogenic fungi and
the results are given in Table 3. Amphotericin was used as a stan-
dard. The compounds showed significant artificial activity only
against Candida rugosa at 100 lg and 150 lg concentrations.
In summary, we have developed a novel method for the
synthesis of 3-(1-(1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-
(3a):
1H
NMR
d

6514
B.V.S. Reddy et al. / Bioorg. Med. Chem. Lett. 21 (2011) 6510–6514
119.6, 119.0, 109.2, 107.3, 101.2, 46.6, 44.7, 39.5, 37.7, 36.8, 36.3; IR (KBr):
3229, 2211, 1700, 1453 cmÀ1; ESI (MS): 367 (M+H).
m
CDCl3 + DMSO, 1:4): d 201.3, 178.1, 142.4, 136.9, 135.0, 132.7, 128.2, 127.9,
127.2, 126.2, 126.0, 123.9, 123.4, 121.0, 120.6, 112.1, 108.7, 101.8, 49.5, 47.3,
44.9, 40.0, 38.7, 37.9; IR (KBr):
3450, 1710, 1435 cmÀ1; ESI (MS): 412 (M+H).
Methyl 3-(2-oxo-1-(2-oxoindolin-3-yl)-2-phenylethyl)-1H-indole-5-carboxylate
(3g): White solid, mp 231–233 °C; 1H NMR (500 MHz, CDCl3 + DMSO, 1:4): d
3.92 (s, 3H), 4.29 (d, 1H, J = 4.1 Hz), 5.61 (d, 1H, J = 4.1 Hz), 6.62 (d, 1H,
J = 7.3 Hz), 6.73–6.79 (m, 1H), 6.94–7.04 (m, 2H), 7.12–7.16 (m, 1H), 7.25–7.47
(m, 4H), 7.68–7.76 (m, 1H), 7.95 (d, 2H, J = 8.3 Hz), 8.50 (s, 1H), 10.0–10.06 (br
s, 1H; NH), 10.81–10.85 (br s, 1H, NH); 13C NMR (75 MHz, CDCl3 + DMSO, 1:4):
d 197.4, 177.7, 167.2, 143.1, 138.5, 135.9, 132.9, 128.6, 128.4, 127.6, 127.5,
3-(2-Oxo-1-(2-oxoindolin-3-yl)-2-phenylethyl)-1H-indole-5-carbonitrile
(3b):
m
White solid, mp 120–122 °C; 1H NMR (300 MHz, CDCl3 + DMSO, 1:4): d 4.21
(d, 1H, J = 3.7 Hz), 5.66 (d, 1H, J = 3.7 Hz), 6.60 (d, 1H, J = 7.7 Hz), 6.75-6.85 (m,
2H), 6.99 (t, 1H, J = 7.1 Hz), 7.23–7.40 (m, 4H), 7.41–7.49 (m, 1H), 7.66 (s, 1H),
7.95 (d, 2H, J = 8.3 Hz), 8.17 (s, 1H), 10.12 (br s, 1H, NH), 11.0 (br s, 1H, NH); 13
C
NMR (75 MHz, CDCl3 + DMSO, 1:4): d 197.12, 177.9, 142.3, 136.9, 134.9, 132.1,
127.8, 127.7, 126.9, 126.5, 125.6, 123.8, 123.4, 120.5, 120.1, 111.8, 108.5, 101.5,
47.4, 45.4, 39.4, 39.1, 38.8; IR (KBr):
m
3255, 2222, 1700, 1468 cmÀ1; ESI (MS):
392 (M+H); 414 (M+Na); HRMS ESI(M+H): Calcd for C25H18N3O2 392.1386.
Found: 392.1399.
125.8, 125.4, 122.3, 121.9, 120.8, 120.6, 109.9, 109, 59.7, 47.1, 45.4; IR (KBr): m
3628, 1694, 1249, 1108 cmÀ1; ESI (MS): 425 (M+H); HRMS (M+H): m/z: Calcd
for C26H20N2O4: 425.1495. Found: 425.1498.
3-(1-(2-methyl-5-nitro-1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-one (3c):
1H NMR (300 MHz, CDCl3 + DMSO, 1:4): d 2.45 (s, 3H), 4.23 (d, 1H, J = 3.5 Hz),
5.67 (d, 1H, J = 3.5 Hz), 6.73–7.51 (m, 9H), 7.86 (d, 2H, J = 8.3 Hz), 8.21 (s, 1H),
10.14 (br s, 1H, NH), 11.08 (br s, 1H, NH); 13C NMR (75 MHz, CDCl3 + DMSO,
1:4): d 201.2, 178.7, 142.7, 137.3, 135.2, 132.5, 128.4, 128.1, 127.7, 126.9, 126.5,
124.7, 124.1, 121.5, 121.0, 112.5, 109.3, 102.7, 51.2, 49.7, 47.9, 45.8, 40.4, 39.1,
3-(1-(2-Methyl-1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-one (3h): 1H NMR
(300 MHz, CDCl3 + DMSO, 1:4): d 2.35 (s, 3H), 4.45 (d, 1H, J = 3.5 Hz), 5.27 (d,
1H, J = 3.5 Hz), 6.63 (d, 1H, J = 7.2 Hz), 6.72–7.53 (m, 6H), 7.62–7.73 (m, 2H),
7.78 (s, 1H), 7.84 (d, 2H, J = 8.1 Hz), 8.07 (s, 1H), 10.07 (br s, 1H, NH), 10.19 (br s,
1H; NH); 13C NMR (75 MHz, CDCl3 + DMSO, 1:4): d 192.1, 174.8, 139.3, 137.8,
132.1, 129.7, 124.9, 123.2, 123.0, 121.9, 121.3, 120.9, 119.7, 118.4, 118.0, 108.7,
38.8; IR (KBr):
m
3610, 2230, 1689, 1472 cmÀ1; ESI (MS): 426 (M+H).
3-(1-(1-Methyl-1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-one (3d): 1H NMR
(300 MHz, CDCl3 + DMSO, 1:4): d 3.92 (s, 3H), 4.16 (d, 1H, J = 3.6 Hz), 5.59 (d,
1H, J = 3.6 Hz), 6.52 (d, 1H, J = 7.4 Hz), 6.68–6.79 (m, 2H), 6.93 (t, 1H, J = 7.0 Hz),
7.16–7.34 (m, 5H), 7.38–7.45 (m, 1H), 7.60 (s, 1H), 7.84 (d, 2H, J = 8.3 Hz), 8.17
(s, 1H), 10.04 (br s, 1H, NH); 13C NMR (75 MHz, CDCl3 + DMSO, 1:4): d 192.4,
175.1, 139.6, 138.0, 132.5, 130.1, 125.0, 123.7, 123.2, 122.0, 121.7, 121.3, 119.9,
118.7, 118.6, 109.0, 106.6, 101.4, 50.7, 46.2, 43.9, 38.9, 37.4, 36.3, 36.0; IR (KBr):
106.1, 100.9, 50.3, 46.0, 43.3, 38.7, 37.2, 36.0, 35.8; IR (KBr):
m 3290, 1693,
1472 cmÀ1; ESI (MS): 381 (M+H).
3-(1-(5-Chloro-1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-one (3i): 1H NMR
(300 MHz, CDCl3 + DMSO, 1:4): d 4.16 (d, 1H, J = 4.1 Hz), 5.50 (d, 1H, J = 4.1 Hz),
6.49–6.54 (m, 2H), 6.69–7.46 (m, 9H), 7.82–7.90 (m, 2H), 9.90–10.04 (br s, 1H,
NH), 10.20–10.26 (br s, 1H, NH); 13C NMR (75 MHz,CDCl3 + DMSO, 1:4): d
196.7, 177.3, 142.7, 135.2, 134.0, 132.2, 128.1, 128.0, 127.8, 127.3, 127.0, 126.8,
m
3310, 1690, 1468 cmÀ1; ESI (MS): 381 (M+H).
124.6, 123.2, 121.0, 120.3, 113.2, 111.4, 108.7, 107.8, 46.9, 44.7; IR (KBr):
m
3-(1-(5-Bromo-1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-one (3e): Orange
color solid, mp 190–192 °C, 1H NMR (300 MHz, CDCl3 + DMSO, 1:4): d 4.22
(d, 1H, J = 4.1 Hz), 5.56 (d, 1H, J = 4.1 Hz), 6.57–6.66 (m, 2H), 6.76–7.53 (m, 9H),
7.88–8.05 (m, 2H), 10.0–10.07 (br s, 1H, NH), 10.45–10.53 (br s, 1H, NH); 13C
NMR (75 MHz, CDCl3 + DMSO, 1:4): d 197.4, 177.9, 143.0, 135.9, 134.6, 132.9,
128.6, 128.5, 128.0, 127.8, 127.6, 127.0, 125.4, 123.8, 121.3, 120.8, 113.6, 111.8,
3496, 1687, 1459, 731 cmÀ1; ESI (MS): 401 (M+H).
3-(2-Oxo-2-phenyl-1-(2-phenyl-1H-indol-3-yl)ethyl)indolin-2-one (3j): 1H NMR
(300 MHz, CDCl3 + DMSO, 1:4): d 4.43 (d, 1H, J = 4.3 Hz) 5.87 (d, 1H, J = 4.3 Hz),
6.82–7.93 (m, 17H), 8.0 (s, 1H), 10.16–10.22 (br s, 1H, NH), 10.93–11.04 (br s,
1H, NH); IR (KBr):
m
3625, 1690, 1457, 735 cmÀ1; ESI (MS): 443 (M+H).
10. (a) Banik, B. K.; Fernandez, M.; Alvarez, C. Tetrahedron Lett. 2005, 46, 2479; (b)
Lin, C.; Hsu, J.; Sastry, M. N. V.; Fang, H.; Tu, Z.; Liu, J.-T.; Yao, C.-F. Tetrahedron
2005, 61, 11751.
11. National Committee for Clinical Laboratory (NCCL), Methods for Dilution
Antimicrobial Susceptibility Tests for Bacteria, which Grows Aerobically, 5th
Ed, Approved Standard M7-A5, NCCLS, Villanova, PA, 2000.
12. Linday, M. E. Practical Introduction to Microbiology; London, E & F. N. Spon Ltd:
United Kingdom, 1962.
109.0, 108.2, 47.0, 45.2; IR (KBr): m
3296, 1687, 1465, 1332, 749 cmÀ1; ESI (MS):
445 (M+H); 467 (M+Na); HRMS (ESI) m/z: Calcd for C24H17N2O2NaBr, 467.0359
(M+Na). Found: 467.0371.
3-(1-(5-Nitro-1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-one (3f): 1H NMR
(300 MHz, CDCl3 + DMSO, 1:4):
d 4.28 (d, 1H, J = 3.9 Hz), 5.73 (d, 1H,
J = 3.9 Hz), 6.78-7.63 (m, 9H), 7.66 (s, 1H), 7.89 (d, 2H, J = 8.6 Hz), 8.21 (s,
1H), 10.14 (br s, 1H, NH), 11.08 (br s, 1H, NH); 13C NMR (75 MHz,