Synthesis and NMR spectral assignments of indol-3-yl pyridines through one-pot multi-component reaction

Article abstract of DOI:10.1002/mrc.2616

Asimple protocol for the efficient preparation of 6-(ferrocene-1-yl)-2- (indol-3-yl)pyridine and 2-(1H-indol-3-yl)-6-(2-thienyl)pyridine derivatives has been achieved through multi-component reaction, and these compounds were thoroughly characterised by 2

Full text of DOI:10.1002/mrc.2616

Spectral Assignments and Reference Data
Received: 21 December 2009
Revised: 17 April 2010
Accepted: 20 April 2010
Published online in Wiley Interscience: 17 May 2010
(www.interscience.com) DOI 10.1002/mrc.2616
Synthesis and NMR spectral assignments
of indol-3-yl pyridines through one-pot
multi-component reaction
Prakasam Thirumurugan,a A. Nandakumar,a Neelakandan Vidhya
Lakshmi,a B. V. N. Phani Kumarb and Paramasivan T. Perumala∗
Asimple protocol for the efficient preparation of 6-(ferrocene-1-yl)-2-(indol-3-yl)pyridine and 2-(1H-indol-3-yl)-6-(2-
thienyl)pyridine derivatives has been achieved through multi-component reaction, and these compounds were thoroughly
c
characterised by 2D NMR spectral techniques. Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: 1H NMR; 13C NMR; 2D NMR; indol-3-yl pyridines; 3-cyanoacetyl indoles
Introduction
distinct peaks appearing in the region of δ = 68.4, 70.0, 71.1,
and 82.5 ppm correspond to ferrocenyl ring carbons in the
13C NMR spectrum and the aromatic carbons appeared in the
region of δ = 112.0–162.7 ppm. The mass spectrum displayed
the molecular ion [M + H]+ peak at m/z 494.20 (Scheme 1)
The structure of compounds 6A–F was confirmed through
spectral and elemental analysis. In the IR spectrum of compound
6B, absorptions at wave numbers 3314 and 2214 cm−1 confirmed
the presence of –NH and –C N functionalities. The 1H NMR
spectrum exhibited a broad singlet at δ = 11.83 ppm (D2O
exchangeable) for –NH protons and a sharp distinguishable
singlet at δ = 2.38 ppm for methyl protons. Aromatic protons
were seen in the region of δ = 7.22–8.51 ppm. A characteristic
peak at δ = 21.4 ppm in the 13C NMR spectrum confirmed the
presence of methyl carbon. The cyano group attached carbon
showed a characteristic peak at δ = 100.7 ppm. The mass
spectrum displayed the molecular ion [M + H]+ peak at m/z
392.27 (Scheme 2).
Due to the vast medicinal applications of the substituted
pyridine derivatives, it is worthwhile to characterise these
compounds with the aid of 1D and 2D NMR spectral studies
such as 1H–1H COSY, HETCOR, HSQC, and HMBC. In order to assign
a chemical shift value to each proton and carbon, atom numbering
was assigned to all derivatives of compounds 4A–E and6A– F.
The chemical shift value of each proton assigned to compounds
4A–E is summarised in Table 1. Noticeable differences in chemical
shiftvaluesduetothesubstituentspresentinthecompound4A–E
wereobserved.TheHETCORandHSQCcorrelationspectragavethe
The structural diversity and biological importance of nitrogen
containing heterocycles have made them attractive targets for
synthesis over many years. They are found in various natural
products and have been identified as products of chemical
and biological importance.[1,2] 3-Substituted indole scaffolds are
found in a number of biologically active compounds especially
with anticancer, antitumour,[3] anti-inflammatory, hypoglycemic,
analgesic, and antipyretic activities.[4] On the other hand, pyridine
substructure is one of the most important heterocycles found
in natural products, pharmaceuticals, and functional materials.[5]
Pyridine derivatives containing multi-functional groups such as
streptonigrin, streptonigrone, and lavendamycin are reported as
anticancer drugs, and cerivastatin is reported as the HMG-CoA
enzyme inhibitors.[6]
The wide-ranging biological activity associated with 3-
substituted indoles and pyridines derivatives, both naturally
occurring and synthetic, ensures that the synthesis of this im-
portant ring system remains a topic of current interest.[7–10]
As part of our ongoing research on the development of novel
synthetic routes for the synthesis of biologically active hetero-
cyclic compounds[11–13] herein, we report the synthesis,[14] 1H
and 13C NMR spectral assignment of 6-(ferrocene-1-yl)-2-(indol-
3-yl)pyridine and (1H-indol-3-yl)-6-(2-thienyl)pyridine derivatives
through 2D NMR spectral techniques in solution.
Results and Discussion
The structure of compounds 4A–E was established based on
the detailed spectroscopic studies, and the elemental analysis as
exemplified for compound 4B as follows: stretching frequencies
at 3416 and 2246 cm−1 in the IR spectrum confirm the presence
of –NH and –C N functional groups. The 1H NMR spectrum
showed chemical shift of δ = 11.14 ppm (brs, D2O exchangeable)
which corresponds to –NH proton, and the aromatic protons
resonated in the region of δ = 7.23–8.70 ppm. The three sharp
∗
Correspondence to: Paramasivan T. Perumal, Organic Chemistry Division,
Central Leather Research Institute, Adyar, Chennai 600 020, India.
E-mail: ptperumal@gmail.com
a
Organic Chemistry Division, Central Leather Research Institute, Adyar, Chennai
600 020, India
b
Chemical Physics Division, Central Leather Research Institute, Adyar, Chennai
600 020, India
c
Magn. Reson. Chem. 2010, 48, 554–561
Copyright ꢀ 2010 John Wiley & Sons, Ltd.

Spectral assignments and reference data
R1
4d
R2
4e
O
4c
4b
4f
CN
O
CHO
4a
4
3a
NH4OAC
NC
5
6
3
Fe
+
+
2d
2g
6b
6d
MeOH,Reflux
2c
6a
2i
R2
2
2e
2f
N
1
6c
N
R1
H
6e
Fe
2b
N
2h
2a
H
1A-E
2
3
4A-E
6f
6f
6f
6f
6f
Aldehydes
R1
H
R2
H
Producta
4A
Time(h)
Yield(%)b
72
1A
1B
1C
6.0
6.5
7.5
7.0
7.5
CH3
Br
4B
4C
4D
4E
76
70
74
75
H
H
1D
1E
F
H
H
NO2
aThe products were characterized by NMR, IR, MASS and elemental analysis.
b Isolated yield.
Scheme 1. Synthesis of 6-(ferrocene-1-yl)-2-(indol-3-yl)pyridine derivative 4A–E from various aldehydes.
1
same information about H–13C correlation connected through
one bond, whereas the HMBC correlation spectrum contained the
information on the 1H–13C correlation connected through two
and three bonds. By combining the HETCOR/HSQC and HMBC
correlation spectra, the 13C chemical shifts for all compounds were
assignedandaresummarisedinTables 2and3(seethesupporting
information).
ring protons appeared at δ = 8.70 and 7.23 ppm and the aromatic
protons were observed at δ = 7.36 and 7.56 ppm.
From the proton assignments in Table 1 and the HETCOR/HSQC
spectra, the chemical shift of carbons was assigned based on their
one-bond coupling with hydrogen. The remaining quaternary
carbon signals were assigned through HMBC spectra. In a similar
fashion, the NMR structural assignments were made for the
compounds 6A–F based on the 2D NMR spectral studies. The
proton chemical shift and coupling constant data are documented
in Table 4. The carbon chemical shifts and HMBC correlations of
compounds(6A–F)aresummarisedinTables 5and6,respectively.
Finally, we have carried out 15N NMR spectral studies on com-
pounds4A–Eand6A–F;however,wewereabletoobserve15Nsig-
nalforthecompound6Bonly.Thedistinctsingletappearingatδ =
−126.69 ppm corresponds to indole –NH nitrogen in the 15N NMR
spectrum (with reference to nitromethane), whereas the other
nitrogens were not observed owing to their long relaxation times.
Based on the detailed 2D NMR spectral studies, the structural
assignments were made for the compounds 4A–E as exemplified
for compound 4B as follows: From the literature, the peaks
appearingatδ = 5.11, 4.54and4.13 ppmcorrespondtoferrocenyl
ring protons. The effect of pyridine ring was manifested by distinct
chemical shifts of ferrocene ring protons δ = 5.11 and 4.54 ppm.
The observation of sharp singlet at 4.13 ppm can be recognised
as the cyclopentadiene ring, connected only to the iron atom. A
broad distinguishable singlet appearing at δ = 11.77 ppm with
D2O exchange corresponds to the indolyl –NH proton. The peaks
at δ = 8.39 and 7.51 ppm did not show any cross-correlation
in the aromatic region of H–1H COSY spectrum. Based on the
1
Conclusions
splitting pattern, the proton chemical shifts were assigned as H-2b
(δ = 8.39 ppm) and H-5 (δ = 7.51 ppm). Based on the cross-peak
In summary, we have demonstrated a simple method for
the synthesis of indol-3-yl pyridine derivatives through multi-
component reaction employing structurally diverse aldehydes
with 3-cyanoacetyl indole and 2-acetyl thiophene (or) 1-acetyl
1
correlations in H–1H COSY spectrum, splitting pattern, integral
values, and coupling constants in the 1H NMR spectrum, the
indolyl ring and phenyl ring protons were assigned. The indolyl
c
Magn. Reson. Chem. 2010, 48, 554–561
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/mrc

P. Thirumurugan et al.
R1
4d
4e
4f
4c
4b
CN
O
CHO
R1
4a
4
NH4OAC
NC
+
5
+
R2
S
3
6c
S
MeOH,Reflux
2d
2g
O
6b
6d
6e
2c
2i
N
H
2e
2f
2
N
6
1
2b
6a
R2
2h
N
H
2a
6A-F
1A-D
5A-B
2
Producta
Time(h)
6.0
R1
H
R2
H
Yield(%)b
72
Aldehydes
1A
6A
6B
6C
6D
6E
6F
1B
1C
1D
1A
1B
CH3
H
H
6.5
7.5
6.5
7.0
7.5
76
70
71
74
75
OMe
F
H
H
Br
Br
CH3
aThe products were characterized by NMR, IR, MASS and elemental analysis.
bIsolated yield.
Scheme 2. Synthesis of 6-(indol-3-yl)-(2-thienyl)pyridine derivative 6A–F from various aldehydes.
ferrocene. 1H and 13C NMR chemical shift values for the newly
synthesised indol-3-yl pyridine derivatives were assigned using
2D NMR techniques.
16,384/32,768, number of scans 8/200, acquisition time 1.3/0.83 s,
relaxation delay 5/2 s, and 90◦ pulse width 12.5/10.2 µs. The
experimental parameters chosen for 15N NMR were as follows:
spectral width 600 ppm, number of data points 16,384, number
scan 1000, acquisition time 0.54 s, relaxation delay 5 s and 90◦
pulsewidth25.4 µs. Exponentialmultiplicationwasappliedbefore
Fourier transformation in both cases.
1H–1H COSY: COSY spectra were obtained using the gradient
version of dqf cosy pulse sequence of the JEOL-Delta software. The
spectra resulted from 1024 (F2) × 256 (F1) data matrix size with
one scan per t1 increment. A spectral width of 15 ppm was used in
both F1 and F2 dimensions.
1H–13C HETCOR: HETCOR spectra were recorded using the
standard hector pulse program of the JEOL-Delta software. The
acquisition parameters were as follows: spectra resulted from
1024 × 128 data matrix size with eight scans per t1 increment.
A spectra width of 180 ppm in F2 and 15 ppm in F1 was
recorded.
1H–13C HSQC: The one-bond correlation of 1H and 13C was
tracked using the phase sensitive HSQC pulse sequence of the
JEOL-Delta software. The experiments were optimised for the
one-bond coupling constant (1JCH) as 140 Hz. The spectra were
obtained from 1024 × 256 data matrix size with four scans per t1
increment. A spectral width of 15 ppm in F2 and 180 ppm in F1
was recorded.
Experimental
General
All the substituted aldehydes, 1-acetyl ferrocene, 2-acetyl thio-
phene, indole, and DMSO-d6 were purchased from Aldrich Chemi-
cals. Acetic anhydride and other reagents were procured from S. D.
Fine Chemicals Ltd. (India), and were used as received. IR spectra
were taken as KBr pellets for solids on a Perkin Elmer spectrum RXI
FT-IR.
All NMR experiments were made on a JEOL ECA-500 MHz
high resolution FT-NMR spectrometer operating at frequencies
500.16 MHz (1H), 125.77 (13C), and 50.68 (15N). An amount of
30 mg of compounds was dissolved in 0.7 ml of DMSO-d6.
Tetramethylsilane was used an internal reference standard for
the assignment of 1H and 13C chemical shifts. 15N chemical shifts
weregivenwithreferencetonitromethaneasaninternalstandard.
All the NMR spectra were recorded at 298 K. JEOL-Delta software
package (version 4.3.6) was used for the purpose of NMR pulse
sequences and data processing.
The experimental parameters chosen for 1D 1H/13C NMR were
as follows: spectral width 15/250 ppm, number of data points
c
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Magn. Reson. Chem. 2010, 48, 554–561

Spectral assignments and reference data
c
Magn. Reson. Chem. 2010, 48, 554–561
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
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P. Thirumurugan et al.
Table 2. 13C chemical shifts of compound 4A–E in DMSO-d6
Entry
2
3
4
5
6
4
2b
2c
2d
2e
2f
2g
2h
2i
4A
4B
4C
4D
4E
163.0
162.7
163.2
163.0
162.3
99.7
99.1
99.2
99.3
99.0
154.3
154.2
153.1
154.3
151.9
116.0
115.5
116.1
116.3
116.0
157.5
157.7
157.5
157.5
157.5
154.3
154.2
153.1
154.3
151.9
129.7
128.3
128.9
128.9
128.6
114.8
113.8
113.5
113.6
113.4
122.8
122.5
122.2
122.2
122.2
123.2
122.6
123.8
122.9
122.9
121.5
120.9
121.3
121.2
121.2
111.5
112.0
112.6
112.6
112.4
136.3
136.7
136.7
136.8
136.7
126.8
126.9
126.9
126.9
126.8
Entry
3a
4a
4b
4c
4d
6a
6b/6e
6c/6d
6fꢁ
4A
4B
4C
4D
4E
119.8
120.0
119.9
119.6
119.5
137.5
134.6
136.9
137.5
139.0
128.7
129.5
131.6
129.4
128.9
128.7
132.2
129.2
127.6
139.6
123.8
130.1
124.1
82.4
82.5
82.5
82.6
82.3
71.2
71.4
71.7
71.6
71.6
68.5
68.4
68.8
68.6
68.8
70.1
70.0
70.3
70.3
70.2
124.5/135.9
148.3/130.7
Table 3. 1H chemical shift and HMBC correlation of compounds 4A–E in DMSO-d6
Entry
4A
4B
4C
4D
4E
Proton
δ1H
m
δ1H
HMBC
δ1H
HMBC
δ1H
HMBC
δ1H
11.79
HMBC
2a
11.77
–
11.14
–
11.78
8.33–8.34
8.51
–
11.76
8.31–8.33
8.51
–
–
2b
8.32–8.33
8.52–8.53
7.15–7.24
2c,2h,2i
2e,2h,2i
–
8.39–8.40
8.70
2c,2h,2i
2e,2h,2i
–
2c,2h,2i
2e,2h
2c,2h,2i
2e
8.35–8.36
8.53–8.53
7.21–7.26
2c,2h,2i
2e
2d
2e
7.23–7.31
7.15–7.24
2i 2g,2h
7.15–7.24
2g,2i 2h
2d 2g
2f
2g
7.15–7.24
7.50–7.56
7.50–7.56
7.50–7.56
7.71–7.73
5.21
2h,2i
4c,4d
4b
7.23–7.31
7.56–7.58
7.36–7.38
–
–
4,4d,4c
4b, 4a
–
7.44–7.51
7.44–7.51
7.74–7.76
–
2e,2i
4, 4a
4b, 4d
–
7.15–7.24
7.41–7.52
7.72–7.78
–
–
4c
7.52–7.61
6.47–6.52, 8.12
6.47–6.52
7.52–7.61
7.88
2f,2h,2i
4,4c
–
4b
4c
4a,4b,4d
–
4d
4b
–
5
3,4,6,6a
6a,6c
6a,6b
–
7.51
3,4
7.66–7.68
5.19
3, 4
7.41–7.52
5.21
3,4
3
6b/6e
6c/6d
6fꢁ
5.11
6a,6c
6a,6b
–
6a,6c
6a,6b
–
6a,6c
6a,6b
5.23
6a,6c
6a,6b
5.47
4.54
4.56
4.57
4.60
4.11
4.13
4.10
4.10
4.12
1H–13C HMBC: The gradient version of HMBC experiments
were recorded in order to sketch the long-range (two and three
bonds) 1H–13C correlations. The long-range coupling constant
(nJCH) optimised was 8 Hz. The spectra resulted from 2048 × 256
data matrix size with eight scans per t1 increment. A spectral width
of 15 ppm in F2 and 180 ppm in F1 was recorded.
the reaction as monitored by TLC, the reaction mixture was poured
into water and extracted with ethyl acetate. The organic layer
was dried over sodium sulfate and concentrated under vacuum.
The crude product was chromatographed, and the appropriate
isolated yield of the pure product is shown in Table 1.
1
2D correlation spectra were recorded in order to track H–1H
6-(Ferrocene-1-yl)-2-(1H-indol-3-yl)-4-(phenyl)nicotinonitrile (4A)
and 1H–13C correlations. A relaxation delay of 1.5 s was used in all
the 2D experiments.
Deep red colour semisolid; Rf 0.38 (20% AcOEt/petroleum ether);
IR (KBr): 1170, 1247, 1445, 1521, 2227, 3421 cm−1; MS (EI):
m/z = 480.20 [M+ + H+]; Anal. Calcd for C30H21FeN3: C 75.17, H
4.42, N 8.77. Found: C 75.06, H 4.43, N 8.79.
Mass spectra were recorded with Thermo Finnigan mass
spectrometer using an electrospray ionisation method. Melting
points were determined in capillary tubes and are uncorrected.
Analytical TLC was performed on precoated plastic sheets of silica
gel G/UV-254 of 0.2 mm thickness (Macherey-Nagel, Germany).
Elemental analysis data were recorded using Thermo Finnigan
FLASH EA 1112 CHN instrument.
6-(Ferrocene-1-yl)-2-(1H-indol-3-yl)-4-(4-
methylphenyl)nicotinonitrile (4B)
Deep red colour semisolid; Rf 0.42 (20% AcOEt/petroleum ether);
IR (KBr): 1119, 1223, 1435, 1526, 1559, 3325 cm−1; MS (EI):
m/z = 494.20 [M+ + H+]; Anal. Calcd for C31H23FeN3: C 75.47, H
4.70, N 8.52. Found: C 75.37, H 4.71, N 8.54.
General procedure for the synthesis of 6-(ferrocene-1-yl)-2-
(indol-3-yl)pyridine derivatives (4A–E)
A mixture of 1-acetyl ferrocene (1 mmol), aldehyde (1 mmol), and
ammonium acetate in methanol was refluxed. After the complete
disappearance of the starting materials (monitored by TLC), 3-
cyanoacetyl indole was added and the reflux was continued for
appropriate time mentioned as in Table 1. After the completion of
6-(Ferrocene-1-yl)-2-(1H-indol-3-yl)-4-(4-
bromophenyl)nicotinonitrile (4C)
Deep red colour semisolid; Rf 0.51 (20% AcOEt/petroleum ether);
IR (KBr): 1168, 1252, 1454, 1642, 2236, 3427 cm−1; MS (EI): m/z =
c
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Magn. Reson. Chem. 2010, 48, 554–561

Spectral assignments and reference data
c
Magn. Reson. Chem. 2010, 48, 554–561
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
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P. Thirumurugan et al.
Table 5. 13C chemical shift of compounds 6A–F in DMSO-d6
Entry
2
3
4
5
6
2b
2c
2d
2e
2f
2g
2h
2i
6A
6B
6C
6D
6E
6F
157.8
157.8
161.0
164.5
157.8
157.8
100.8
100.7
100.6
100.8
101.2
101.1
154.5
154.2
155.1
157.7
153.1
153.0
114.9
114.9
114.7
114.9
114.5
112.8
155.5
155.4
161.1
162.5
155.5
155.4
129.3
129.5
129.3
129.3
129.2
129.3
113.0
113.0
113.0
112.9
112.8
114.3
128.9
128.9
128.7
128.9
129.2
129.1
123.0
123.0
123.0
123.1
123.0
122.9
121.4
121.3
121.3
121.4
121.5
121.4
112.6
112.6
112.6
112.6
112.6
112.6
136.3
136.8
136.9
136.9
136.9
136.7
126.6
126.6
126.6
126.6
126.5
126.5
Entry
3a
4a
4b
4c
4d
6b
6c
6d
6e
6A
6B
6C
6D
6E
6F
119.5
144.2
140.1
144.2
144.1
145.9
140.0
129.4
129.8
130.9
129.2
129.3
114.8
130.2
142.2
154.1
137.3
134.2
131.5
133.6
117.6
117.4
122.3
122.3
122.3
122.3
122.1
122.1
129.3
129.8
129.5
129.5
132.8
132.8
131.7
131.4
130.7
131.7
137.1
134.1
119.7
119.8
119.5
119.4
119.5
131.8 (d, JC2 –F = 38.3 Hz)
116.1 (d, JC1 –F = 85.9 Hz)
154.2 (d, JC1 –F = 85.9 Hz)
129.3
129.2
129.1
129.7
130.2
145.8
Table 6. 1H chemical shift and HMBC correlation in DMSO-d6 of compounds 6A–F
Entry
6A
6B
6C
6D
6E
6F
Proton
δ1H
HMBC
δ1H
HMBC
δ1H
HMBC
δ1H
HMBC
–
δ1H
11.85
HMBC
2c,2h,2i
δ1H
HMBC
2a
2b
2d
2e
2f
11.83
8.40
8.12
–
2c,2h,2i
–
11.83
8.39
8.10
2b,2c,2h
11.82
8.37
8.08
–
11.84
8.37
11.83
–
2c,2h,2i
2c,2h,2i
2c,2h,2i 8.38–8.42 2c,2h,2i 8.37–8.39
2h,2i
–
–
8.08
–
7.85
7.24–7.27
7.24–7.27
7.52
–
2d
7.79
7.21–7.28
7.21–7.28
7.52
–
7.22–7.24
7.22–7.24
7.57
2i
7.22–7.24
7.22–7.24
7.52
–
7.20–7.23
2i
7.19–7.24
2g,2i
–
2g,2h
2f,2h,2i
4c,4d
4b
–
7.20–7.23 2e,2g,2h 7.19–7.24
2h
2g
–
2g
4b
4c
4d
5
2f,2i
7.51
7.69
2e,2i
7.77–7.83
7.77–7.83
7.39
–
2f,2h,2i
4,4c
–
2f,2i
7.73
7.62
4,4a,4c
4
4c
7.66
7.52
4,4a,4c
7.57
7.36
4b, –CH3
7.01
–
4a,4b,4d
7.52
7.27
–
–
7.57
4b
–
–
–
–
–
–
3,4a,6b
–
7.52
–
–
7.90
3,4,6,6b
6b
7.86
3,4,6b
7.84
3,4a,6
7.87
7.79
3,4a,6
–
7.71
3,6
–
6c
6d
6e
8.52
8.51
–
–
–
8.49
–
–
–
8.49
8.38–8.42
7.24–7.27
–
8.34
7.22–7.74
7.81
6c
7.22–7.24
7.81
7.20–7.23
7.79
7.19–7.24
7.52
6c
6c
7.21–7.28
–
–
6d
6c
–
–
558.07 [M+ + H+]; Anal. Calcd for C30H20BrFeN3: C 64.54, H 3.61, N
disappearance of starting materials (monitored by TLC), 3-
cyanoacetyl indole was added and the reflux was continued for
appropriate time mentioned as in Table 2. After the completion
of the reaction (as monitored by TLC), the solid was filtered and
then dried. The crude solid was recrystallised with ethanol and
appropriate isolated yield was shown in Table 2.
7.53. Found: C 64.62, H 3.60, N 7.55.
6-(Ferrocene-1-yl)-2-(1H-indol-3-yl)-4-(4-fluorophenyl)nicotinonitrile
(4D)
Deep red colour semisolid; Rf 0.56 (20% AcOEt/petroleum ether);
IR (KBr): 1142, 1348, 1567, 1638, 2236, 3422 cm−1; MS (EI):
m/z = 498.07 [M+ + H+]; Anal. Calcd for C30H20FFeN3: C 72.45, H
4.05, N 8.45. Found: C 72.56, H 4.06, N 8.43.
2-(1H-indol-3-yl)-4-phenyl-6-(2-thienyl)nicotinonitrile (6A)
Yellowsolid;mp248–250 ◦C;Rf 0.37(20%AcOEt/petroleumether);
IR (KBr): 1136, 1231, 1566, 2216, 3302 cm−1; MS (EI): m/z = 378.27
[M+ + H+]; C24H15N3S. Anal. Calcd. for C24H15N3S: C 76.37, H 4.01,
N 11.13. Found: C 76.20, H 4.00, N 11.16.
6-(Ferrocene-1-yl)-2-(1H-indol-3-yl)-4-(3-nitrophenyl)nicotinonitrile
(4E)
Deep red colour semisolid; Rf 0.45 (20% AcOEt/petroleum ether);
IR (KBr): 1052, 1246, 1451, 1621, 2238, 3452 cm−1; MS (EI):
m/z = 526.13 [M+ + H+]; Anal. Calcd for C30H20FeN4O: C 68.72, H
3.84, N 10.68. Found: C 68.63, H 3.85, N 10.65.
2-(1H-indol-3-yl)-4-(4-methylphenyl)-6-(2-thienyl)nicotinonitrile
(6B)
General procedure for the synthesis of 2-(indol-3-yl)-6-(2-
thienyl)pyridine derivatives (6A–F)
Yellowsolid;mp283–285 ◦C;Rf 0.40(20%AcOEt/petroleumether);
IR (KBr): 1528, 1652, 2214, 2930, 3314 cm−1; MS (EI): m/z = 392.27
[M+ + H+]; C25H17N3S. Anal. Calcd for C25H17N3S: C 76.70, H 4.38,
N 10.73. Found: C 76.82, H 4.36, N 10.70.
A mixture of 2-acetyl thiophene (1 mmol), aldehyde (1 mmol), and
ammonium acetate in MeOH was refluxed. After the complete
c
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Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2010, 48, 554–561

Spectral assignments and reference data
2-(1H-indol-3-yl)-4-(4-methoxylphenyl)-6-(2-thienyl)nicotinonitrile
(6C)
Supporting information
Supporting information may be found in the online version of this
article.
Yellow solid; mp 218–220 ◦C; Rf 0.29 (20% AcOEt/petroleum
ether); IR (KBr): 1248, 1516, 1635, 2370, 2918, 3309 cm−1; MS (EI):
m/z = 408.20[M+ +H+];C25H17N3OS.Anal.CalcdforC25H17N3OS:
C 73.69, H 4.21, N 10.31. Found: C 73.54, H 4.20, N 10.34.
References
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4-(4-Fluorophenyl)-2-(1H-indol-3-yl)-6-(2-thienyl)nicotinonitrile (6D)
Yellow solid; mp 288–290 ◦C; Rf 0.46 (20% AcOEt/petroleum
ether); IR (KBr): 1025, 1428, 1620, 2369, 2922, 3304 cm−1; MS (EI):
m/z = 396.33 [M+ + H+]; C24H14FN3S. Anal. Calcd for C24H14FN3S:
C 72.89, H 3.57, N 10.63. Found: C 72.75, H 3.56, N 10.66.
6-(5-Bromo-2-thienyl)-2-(1H-indol-3-yl)-4-phenylnicotinonitrile (6E)
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M. D. Hill, O. K. Ahmad, J. Am. Chem. Soc. 2007, 129, 10096.
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(b) M. A. A. Radwan, E. A. Ragab, N. M. Sabrya, S. M. El-Shenawyc,
Bioorg. Med. Chem. 2007, 15, 3832.
Yellowsolid;mp208–210◦C;Rf 0.37(20%AcOEt/petroleumether);
IR (KBr): 1421, 1623, 2210, 3413 cm−1; MS (EI): m/z = 456.13 [M+ +
H+]; C24H14BrN3S. Anal. Calcd for C24H14N3BrS: C 63.16, H 3.09, N
9.21. Found: C 63.08, H 3.10, N 9.24.
[9] T. A. Abdallah, J. Heterocyclic Chem. 2007, 44, 961.
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19, 3611; (b) P. Thirumurugan, A. Nandakumar, D. Muralidharan,
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6-(5-Bromo-2-thienyl)-2-(1H-indol-3-yl)-4-(4-
methylphenyl)nicotinonitrile (6F)
Yellowsolid;mp234–236◦C;Rf 0.34(20%AcOEt/petroleumether);
IR (KBr): 1528, 1652, 2214, 2930, 3314 cm−1; MS (EI): m/z = 470.20
[M+ + H+]; C25H16BrN3S. Anal. Calcd for C25H16BrN3S: C 63.83, H
3.43, N 8.93. Found: C 63.93, H 3.42, N 8.95.
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Acknowledgment
The authors P. Thirumurugan and A. Nandakumar thank the
Council of Scientific and Industrial Research, New Delhi, India, for
the research fellowship.
c
Magn. Reson. Chem. 2010, 48, 554–561
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
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