Unusual formation of novel highly substituted N-(3-indolyl)-imidazoles

Article abstract of DOI:10.1016/j.tet.2018.11.007

Treatment of 3-amidoindoles with phosphoryl chloride leads to a dimerization of the resulting iminochlorides to form tetrasubstituted imidazoles in moderate yield. One indole ring undergoes ring-opening to allow the formation of the imidazole ring. This s

Full text of DOI:10.1016/j.tet.2018.11.007

Accepted Manuscript
Unusual formation of novel highly substituted N-(3-indolyl)-imidazoles
Ji Qu, Mohan Bhadbhade, Naresh Kumar, David StC. Black
PII:
S0040-4020(18)31334-6
https://doi.org/10.1016/j.tet.2018.11.007
TET 29918
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 8 October 2018
Revised Date: 2 November 2018
Accepted Date: 5 November 2018
Please cite this article as: Qu J, Bhadbhade M, Kumar N, Black DS, Unusual formation of novel highly
substituted N-(3-indolyl)-imidazoles, Tetrahedron (2018), doi: https://doi.org/10.1016/j.tet.2018.11.007.
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Unusual formation of novel highly
substituted N-(3-indolyl)-imidazoles
Ji Qu, Mohan Bhadbhade, Naresh Kumar, David StC. Black*
O
R
N
Ph
H
O
HN
N
R
Ph
R
N
N
H
Ph
N
H
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Tetrahedron
1
Unusual formation of novel highly substituted N-(3-indolyl)-
imidazoles
Ji Qu, Mohan Bhadbhade, Naresh Kumar, David StC. Black*
School of Chemistry, The University of New South Wales, UNSW Sydney, NSW 2052, Australia
Abstract— . © 2018 Elsevier Science. All rights reserved Treatment of 3-amidoindoles with phosphoryl chloride leads to a dimerization
of the resulting iminochlorides to form tetrasubstituted imidazoles in moderate yield. One indole ring undergoes ring-opening to allow the
formation of the imidazole ring. This strategically simple synthesis considerably expands the scope of delivering N-indolylimidazoles.
Keywords: indoles, 3-aminoindoles, 3-amidoindoles, imidazoles, N-indolylimidazoles
1. Introduction
Imidazoles are commonly synthesized from 1,2-dicarbonyl
Me
compounds and aldehydes in the presence of ammonia.1,2
Me
O
HN
NOH
Ph
(i)
Tetraphenyl imidazoles can be synthesized from benzoin,
aniline and benzaldehydes,3 or from benzil, benzonitrile
and aniline or related primary amines.4-6
Ph
R
Me
Ph
N
H
N
H
a
b
c
d
e
f
3a
1
4-BrC6H4
4-ClC6H4
4-FC6H4
Although highly substituted imidazoles are well known in
the literature, compounds linking indole and imidazole
rings are not common. However, the indole-imidazole
structure features in some bioactive alkaloids.
Granulatimide and isogranulatimide, isolated from the
Brazilian ascidian Didemmum granulatum,7-9 are strong G2
checkpoint inhibitors,10 and have been synthesized.11 These
link the indole through C2 to the imidazole C4 and N1
respectively. The bicyclic peptide moroidin, which shows
potent inhibitory activity on tubulin assembly, has been
isolated from the seeds of Celosia argentea12 and the leaves
of Laportea moroides,13,14 and has also been synthesized.15
The linkage in this case is also from the indole C2 to the
imidazole N1. The nortopsentins and topsentins, isolated
from deep-sea sponges, and which show potent anti-cancer
activity, contain indole rings attached through their C3
positions to C2 and C4 positions of an imidazole ring. For
example, topsentin A has been isolated from Topsentia
(ii)
R
4-MeOC6H4
O
NH2
HN
(iii)
Ph
Ph
N
H
N
H
2
3b-f
(iv)
R
N
N
H
4
Scheme 1. Conditions: (i) conc. H2SO4, MeCN, 64%; (ii)
conc. H2SO4, 60%; (iii) RCOCl, 18-51%; (iv) P2O5, 26-
67%.
genitrix16 and nortopsentin
A
from Spongosorites
ruetzleri.17 The nortopsentins have also been synthesized.18
During the course of the investigation of this Bischler-
Napieralski cyclisation, the amides 3a-f were heated in
phosphoryl chloride for 3-5 h and unexpectedly gave the
imidazoles 5a-f in moderate yields (Scheme 2).
We now describe a completely new and unusual synthesis
of N-indolylimidazoles. We have previously reported the
synthesis of a range of 3-amido-2-arylindoles 3 from 2-
phenylindole-3-acetoxime 119.
The oxime 1 directly
underwent the Beckmann rearrangement to give the 3-
amidoindole 3a. It was also converted by treatment with
concentrated sulfuric acid into 3-amino-2-phenylindole 22,
which was then acylated with a range of benzoyl chlorides
to yield the 3-amidoindoles 3b-f. These amides were
subsequently converted into a range of indoloquinolines 4,
by heating them overnight with P2O5 in toluene (Scheme
1).

ACCEPTED MANUSCRIPT
2
Tetrahedron
A feasible mechanism of the reaction could involve an
O
intermolecular coupling of two imino chlorides. The
reaction of 3-amidoindoles with phosphoryl chloride would
be expected to give imino chlorides, which could undergo
dimerisation to form the imidazole ring (Scheme 3).
Formation of the aromatic imidazole ring would be
favoured and would result in the formation of a 2-
benzamido substituent at the imidazole C4 position.
R
N
Ph
H
O
HN
(i)
N
R
Ph
R
N
N
H
Ph
R
Yield %
_____________________
N
3a-f
H
a
b
c
d
e
f
Me
Ph
4-BrC6H4
4-ClC6H4
4-FC6H4
4-MeOC6H4
40
46
31
52
44
52
5a-f
R
NH
Cl
O
R
HN
Ph
N
N
Ph
R
Cl
N
H
N
Ph
H
3a-f
Scheme 2. Conditions: (i) POCl3, 110 ˚C, 3 h, 31-52%.
O
H2O
H
2. Results and Discussion
N
Ph
N
H
Ph
N
2.1. Synthesis of indolylimidazoles
N
Cl
R
R
Cl
R
N
R
N
The 3-amidoindoles 3a-f were dissolved in phosphoryl
chloride and heated under reflux for several hours and the
red solutions were neutralised with sodium hydroxide. The
yellow needle-like products were purified by
chromatography and recrystallisation. The 1H NMR
spectrum of compound 5b showed the amide NH signal at
δ 11.76 ppm, which indicated that the amide group was
different from that of the 3-amidoindole 3b. Also, the
integration of the protons in the aromatic region from 6.77-
8.62 ppm was doubled, and indicated the presence of four
aryl rings. The indolo-imidazole structure was confirmed
by an X-ray crystal structure of compound 5b (Figure 1).
Ph
Ph
N
N
H
H
5a-f
Scheme 3: Possible mechanism for the formation of
imidazoles 5a-f.
This simply-performed reaction represents a completely
new synthetic approach to imidazoles. Although it does not
allow wide scope, it should be adaptable to include amides
derived from indoles with 2-substituents other than phenyl,
and also with substituents in positions C4 to C7. It
inevitably leads to tetrasubstituted imidazoles and is
probably limited to amidoindoles.
Preliminary biological testing for the new indole-
imidazoles 5a-f indicates that they show antibacterial
activity against Staphylococcus aureus and weak activity
against Escherichia coli.
3. Conclusions
Treatment of 3-amidoindoles with phosphoryl chloride
leads to a dimerization of the resulting iminochlorides to
form tetrasubstituted imidazoles in moderate yield. One
indole ring undergoes ring-opening to allow the formation
of the imidazole ring. This strategically simple synthesis
considerably expands the scope of delivering N-
indolylimidazoles.
Figure 1. ORTEP diagram of the crystal structure of
compound 5b.
The new imidazole ring is fully substituted by an initial
indole substituent at N1, the aryl amide at C4, and the two
initial benzamide arene rings at C2 and C5. Also, while one
of the 2-phenylindole substituents remains intact, the other
indole ring has been opened to give an aryl amide.

ACCEPTED MANUSCRIPT
Tetrahedron
3
4. Experimental
4.1. General
spectrum (300 MHz, DMSO-d6): δ 2.07 (3H, s, Me), 2.48
(3H, s, Me), 7.11-7.19 (2H, m, ArH), 7.24-7.34 (8H, m,
ArH), 7.47-7.56 (5H, m, ArH), 8.01 (2H, d, J 7.8 Hz, ArH),
8.62 (1H, d, J 7.8 Hz, ArH), 12.09 (1H, s, NHCO), 12.79
(1H, br s, NH). 13C NMR (DMSO-d6, 75.5 MHz): δ 10.7
(Me), 13.1 (Me), 111.6 (Ar-CH), 117.6 (Ar-CH), 121.5
(Ar-CH), 123.2 (Ar-C), 123.7 (Ar-CH), 125.5 (3 x Ar-CH),
125.6 (Ar-C), 127.0 (Ar-C), 127.5 (3 x Ar-CH), 128.1 (Ar-
C), 128.3 (4 x Ar-CH), 128.7 (Ar-C), 129.4 (3 x Ar-CH),
129.7 (Ar-C), 131.2 (Ar-CH), 133.1 (Ar-C), 134.4 (Ar-C),
135.7 (Ar-C), 136.9 (Ar-C), 144.4 (C=N), 165.4 (CO).
HRMS (ESI+): found m/z 483.2179, [M+H+], C32H27N4O
requires 483.2185).
Melting points were measured using a Mel-Temp melting
point apparatus, and are uncorrected. Microanalyses were
performed on a Carlo Erba Elemental Analyser EA 1108 at
the Campbell Microanalytical Laboratory, University of
Otago, New Zealand. 1H and 13C NMR spectra were
obtained on a Bruker DPX300 (300 MHz) spectrometer.
Mass spectra were recorded on either a Bruker FT-ICR MS
(EI) or a Micromass ZQ2000 (ESI) at UNSW, or a
Shimadzu LCMS QP 8000 (ESI) at the University of
Otago, New Zealand. Infrared spectra were recorded with
a Thermo Nicolet 370 FTIR Spectrometer using KBr discs.
Ultraviolet-visible spectra were recorded using a Varian
Cary 100 Scan Spectrometer. Column chromatography was
carried out using Merck 230-400 mesh ASTM silica gel,
whilst preparative thin layer chromatography was
performed using Merck silica gel 7730 60GF254.
4.3.4. N-(2-(2,5-Diphenyl-1-(2-phenyl-1H-indol-3-yl)-
1H-imidazol-4-yl)phenyl) benzamide (5b)
This was prepared from 3-benzamido indole 3b (0.1 g, 0.6
mmol) in phosphoryl chloride (3mL) during 3 h to yield
indolylimidazole 5b (0.09 g, 46%) as a white solid. mp
287-289 °C. (found: C, 81.8; H, 5.2; N, 9.0. C42H30N4 O 0.5
H2O requires C, 81.9; H, 5.1; N, 9.0 %.) νmax (KBr): 3225,
1647, 1585, 1538, 1491, 1471, 1451, 1326, 1260, 744, 696
cm-1. λmax (MeOH): 226 nm (ε 82,700 cm-1M-1), 300
(33,800). 1H NMR spectrum (300 MHz, DMSO-d6): δ 6.78
(1H, t, J 7.4 Hz, ArH), 6.83-7.33 (20H, m, ArH), 7.34-7.38
(4H, m, ArH), 7.49 (1H, t, J 7.4 Hz, ArH), 7.98 (2H, d, J
7.4 Hz, ArH), 8.59 (1H, d, J 7.4 Hz, ArH), 11.76 (1H, s,
NHCO), 12.89 (1H, br s, NH). 13C NMR (DMSO-d6, 75.5
MHz): δ 109.2 (Ar-C), 112.3 (Ar-CH), 117.5 (Ar-CH),
121.2 (Ar-CH), 121.3 (Ar-CH), 122.0 (Ar-C), 123.2 (Ar-
CH), 125.9 (2 x Ar-CH), 126.1 (Ar-C), 127.5 (2 x Ar-CH),
127.7 (2 x Ar-CH), 127.9 (Ar-CH), 128.7 (8 x Ar-CH),
128.8 (Ar-CH), 129.0 (2 x Ar-CH), 129.3 (2 x Ar-CH),
129.8 (Ar-C), 130.1 (2 x Ar-C), 130.4 (2 x Ar-CH), 132.1
(Ar-CH), 133.6 (2 x Ar-C), 134.5 (Ar-C), 135.4 (Ar-C),
136.5 (Ar-C), 137.2 (Ar-C), 146.7 (C=N), 164.7 (CO).
HRMS (ESI+): found m/z 607.2493, [M+H+], C42H31N4O
requires 607.2498).
Crystallographic data for the structure of compound 5b
have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication no. CCDC
769425.
4.2. Synthesis of 3-amidoindoles
The 3-amidoindoles 5a-f have been reported in our
previous work.1
4.3.1. Synthesis of N-(3-indolyl)-imidazoles
4.3.2. General preparative method
The 3-amidoindole was dissolved in phosphoryl chloride
and heated at 110-120 C for 3-5 h. The resulting red
o
solution was poured into ice water, and neutralized with
2M sodium hydroxide solution. The mixture was allowed
to cool to room temperature with thorough stirring, then
extracted with ethyl acetate and dried over anhydrous
sodium sulfate. After concentration under reduced pressure,
the residue was purified by column chromatography and
eluted with dichloromethane/light petroleum (70:30) to
give the indolylimidazole. Recrystallization from ethanol
resulted in yellow needles.
4.3.5. N-(2-(2,5-bis(4-Bromophenyl)-1-(2-phenyl-1H-
indol-3-yl)-1H-imidazol-4-yl) phenyl)benzamide (5c)
This was prepared from 3-benzamidoindole 3c (0.1 g, 0.25
mmol) in phosphoryl chloride (3 mL) during 3.5 h to yield
indolylimidazole 5c (0.03 g, 31%) as a yellow solid. mp
165-168 °C. (found: C, 65.4; H, 4.2; N, 7.0. C42H28Br2N4O
0.5 H2O requires C, 65.2; H, 3.8; N, 7.2 %.) νmax (KBr):
3413, 3255, 1656, 1614, 1585, 1537, 1487, 1455, 1314,
1260, 1071, 1010, 966, 826, 745, 705, 693 cm-1. λmax
4.3.3. N-(2-(2,5-Dimethyl-1-(2-phenyl-1H-indol-3-yl)-
1H-imidazol-4-yl)phenyl) benzamide (5a)
This was prepared from indole-3-amide 3a (0.1 g, 0.4
mmol) in phosphoryl chloride (3 mL) during 3 h to yield
indolylimidazole 5a (0.04 g, 40%) as a brown solid. mp
268-270 °C. (found: C, 78.9; H, 5.5; N, 11.2. C32H26N4O
0.25 H2O requires C, 78.9; H, 5.6; N, 11.5 %.) νmax (KBr):
3185, 3059, 1649, 1618, 1584, 1545, 1521, 1455, 1399,
1327, 1262, 744, 693 cm-1. λmax (MeOH): 202 nm (ε
1
(MeOH): 229 nm (ε 92,400 cm-1M-1), 301 (48,300). H
NMR spectrum (300 MHz, DMSO-d6): δ 6.88-6.93 (2H, m,
ArH), 6.98-7.09 (5H, m, ArH), 7.10-7.33 (10H, m, ArH),
7.40 (4H, d, J 8.4 Hz, ArH), 7.51 (1H, t, J 7.6 Hz, ArH),
7.95 (2H, d, J 7.6 Hz, ArH), 8.50 (1H, d, J 7.6 Hz, ArH),
11.87 (1H, s, NHCO), 12.40 (1H, br s, NH). 13C NMR
(DMSO-d6, 75.5 MHz): δ 108.8 (Ar-C), 112.5 (Ar-CH),
161,300 cm-1M-1), 204 (160,700), 302 (44,000). H NMR
1

ACCEPTED MANUSCRIPT
4
Tetrahedron
117.4 (Ar-CH), 121.3 (Ar-CH), 121.8 (Ar-CH), 122.4 (Ar-
C), 123.5 (Ar-CH), 123.6 (Ar-CH), 125.8 (Ar-C), 125.9 (2
x Ar-CH), 127.5 (2 x Ar-CH), 128.2 (Ar-CH), 128.5 (Ar-
C), 128.7 (Ar-CH), 128.8 (Ar-C), 128.9 (2 x Ar-CH), 129.0
(Ar-C), 129.1 (Ar-C), 129.2 (Ar-CH), 129.3 (2 x Ar-CH),
129.4 (2 x Ar-CH), 131.6 (2 x Ar-CH), 131.7 (2 x Ar-CH),
132.2 (Ar-CH), 132.3 (2 x Ar-CH), 133.5 (Ar-C), 133.7
(Ar-C), 134.2 (Ar-C), 134.5 (Ar-C), 135.4 (Ar-C), 137.1
(Ar-C), 137.3 (Ar-C), 145.9 (C=N), 165.1 (CO). HRMS
(ESI+): found m/z 763.0703, [M+H+], C42H29Br2N4O
requires 763.0708).
126.0 (Ar-C), 126.1 (2 x Ar-CH), 126.5 (Ar-C), 126.6 (Ar-
C), 126.7 (Ar-C), 127.6 (2 x Ar-CH), 128.2 (Ar-CH), 128.9
(Ar-CH), 129.1 (3 x Ar-CH), 129.5 (2 x Ar-CH), 129.9
(Ar-C), 130.1 (Ar-CH), 130.2 (Ar-CH), 132.4 (Ar-CH),
132.5 (Ar-C), 132.8 (Ar-CH), 132.9 (Ar-CH), 133.8 (Ar-
C), 134.7 (Ar-C), 135.5 (Ar-C), 136.9 (Ar-C), 137.4 (Ar-
C), 146.1 (C=N), 164.9 (CO). HRMS (ESI+): found m/z
643.2304, [M+H+], C42H29F2N4O requires 643.2309).
4.3.8. N-(2-(2,5-bis(4-Methoxyphenyl)-1-(2-phenyl-1H-
indol-3-yl)-1H-imidazol-4-yl)phenyl)benzamide (5f)
4.3.6. N-(2-(2,5-bis(4-Chlorophenyl)-1-(2-phenyl-1H-
indol-3-yl)-1H-imidazol-4-yl) phenyl)benzamide (5d)
This was prepared from 3-benzamido indole 3f (0.1 g, 0.3
mmol) in phosphoryl chloride (3 mL) during 5 h to yield
indolylimidazole 5f (0.05 g, 52%) as a yellow solid. mp
175-178 °C. (found: C, 79.0; H, 5.4; N, 8.2. C44H34N4O3
0.25 H2O requires C, 78.7; H, 5.2; N, 8.3 %.) νmax (KBr):
3255, 3059, 1654, 1613, 1585, 1526, 1507, 1494, 1452,
1386, 1313, 1293, 1250, 1175, 833, 746, 706 cm-1. λmax
This was prepared from 3-benzamidoindole 3d (0.1 g, 0.29
mmol) in phosphoryl chloride (3 mL) during 3.5 h to yield
indolylimidazole 5d (0.05 g, 52%) as a yellow solid. mp
166-169 °C. (found: C, 74.9; H, 4.4; N, 8.2. C42H28Cl2N4O
requires C, 74.7; H, 4.2; N, 8.3 %.) νmax (KBr): 3260, 3060,
1655, 1617, 1586, 1537, 1489, 1451, 1410, 1313, 1259,
1091, 1014, 965, 830, 764, 745, 705, 693 cm-1. λmax
1
(MeOH): 229 nm (ε 61,000 cm-1M-1), 284 (21,900). H
NMR spectrum (300 MHz, DMSO-d6): δ 3.59 (3H, s,
OMe), 3.66 (3H, s, OMe), 6.20 (2H, d, J 8.4 Hz, ArH), 6.73
(2H, d, J 8.4 Hz, ArH), 6.79-6.90 (3H, m, ArH), 6.99-7.04
(2H, m, ArH), 7.12-7.34 (12H, m, ArH), 7.39 (1H, d, J 8.4
Hz, ArH), 7.52 (1H, t, J 8.4 Hz, ArH), 7.99 (2H, d, J 8.4
Hz, ArH), 8.59 (1H, d, J 8.4 Hz, ArH), 11.72 (1H, s,
NHCO), 12.92 (1H, br s, NH). 13C NMR (DMSO-d6, 75.5
MHz): δ 55.3 (OCH3), 55.5 (OCH3), 109.5, 112.4 (Ar-CH),
114.1 (4 x Ar-CH), 117.5 (Ar-CH), 121.2 (2 x Ar-CH),
122.1 (Ar-C), 122.2 (Ar-C), 122.3 (Ar-C), 123.2 (Ar-CH),
123.3 (Ar-CH), 125.9 (2 x Ar-CH), 126.4 (Ar-C), 127.5 (2
x Ar-CH), 127.7 (Ar-CH), 128.6 (Ar-CH), 128.7 (Ar-CH),
129.0 (2 x Ar-CH), 129.1 (2 x Ar-CH), 129.3 (2 x Ar-CH),
130.0 (Ar-C), 130.2 (Ar-CH), 131.8 (2 x Ar-CH), 132.2
(Ar-CH), 133.1 (Ar-C), 133.5 (Ar-C), 134.5 (Ar-C), 135.4
(Ar-C), 136.1 (Ar-C), 137.2 (Ar-C), 146.5 (PhOCH3),
159.4 (PhOCH3), 159.9 (C=N), 164.8(CO). HRMS (ESI+):
found m/z 667.2704, [M+H+], C44H35N4O3 requires
667.2709).
(MeOH): 229 nm (ε 100,600 cm-1M-1), 300 (63,700). H
1
NMR spectrum (300 MHz, DMSO-d6): δ 6.89-7.03 (5H, m,
ArH), 7.09-7.19 (5H, m, ArH), 7.21-7.33 (11H, m, ArH),
7.40 (1H, d, J 8.1 Hz, ArH), 7.52 (1H, t, J 7.3 Hz, ArH),
7.95 (2H, d, J 8.1 Hz, ArH), 8.51 (1H, d, J 8.1 Hz, ArH),
11.84 (1H, s, NHCO), 12.42 (1H, br s, NH). 13C NMR
(DMSO-d6, 75.5 MHz): δ 108.7 (Ar-C), 112.5 (Ar-CH),
117.4 (Ar-CH), 121.3 (Ar-CH), 121.7 (Ar-CH), 122.3 (Ar-
C), 123.5 (Ar-CH), 123.6 (Ar-CH), 125.7 (Ar-C), 126.0 (2
x Ar-CH), 127.5 (3 x Ar-CH), 128.2 (Ar-CH), 128.6 (Ar-
C), 128.7 (Ar-CH), 128.8 (4 x Ar-C), 128.9 (3 x Ar-CH),
129.2 (3 x Ar-CH), 129.4 (2 x Ar-CH), 129.9 (Ar-C), 132.2
(2 x Ar-CH), 132.4 (Ar-C), 133.7 (Ar-C), 134.1 (Ar-C),
134.6 (Ar-C), 135.3 (Ar-C), 137.2 (Ar-C), 137.2 (Ar-C),
145.9 (C=N), 164.7 (CO). HRMS (ESI+): found m/z
675.1713, [M+H+], C42H29Cl2N4O requires 675.1718).
4.3.7. N-(2-(2,5-bis(4-Fluorophenyl)-1-(2-phenyl-1H-
indol-3-yl)-1H-imidazol-4-yl) phenyl)benzamide (5e)
5. References
1. Grimmett, M. R. Science of Synthesis 2002, 12, 325-
528; Ed. Neier, R., Thieme, Stuttgart, Germany.
2. Xi, N.; Huang, Q.; Liu, L. Comprehensive Heterocyclic
Chemistry III 2008, 4, 143-365; Ed. Katritzky, A. R.;
Ramsden, C. A.; Scriven, E. F. V.; Taylor, R. J. K.; Vol.
Ed. Joule, J., Elsevier, Oxford, UK.
This was prepared from 3-benzamidoindole 3e (0.07 g, 0.2
mmol) in phosphoryl chloride (3 mL) during 5 h to yield
indolylimidazole 5e (0.03 g, 44%) as a yellow solid. mp
267-269 °C. (found: C, 75.6; H, 4.3; N, 8.4. C42H28F2N4O
1.25 H2O requires C, 75.8; H, 4.6; N, 8.4 %.) νmax (KBr):
3416, 3278, 1661, 1586, 1523, 1506, 1493, 1451, 1384,
1322, 1232, 1158, 837, 746, 693 cm-1. λmax (MeOH): 229
3. Kidwai, M.; Mothsra, P. Tetrahedron Lett. 2006, 47,
5029-5031.
1
nm (ε 100,000 cm-1M-1), 298 (54,100). H NMR spectrum
4. Radziszewski, Nature, 1882, 15, 1493.
5. Frantz, D. E.; Morency, L.; Soheili, A.; Murry, J. A.;
Grabowski, E. J. J.; Tillyer, R. D. Org. Lett. 2004, 6,
843-846.
6. Balalaie,S.; Hashemi, M. M.; Akhbari, M. Tetrahedron
Lett. 2003, 44, 1709-1711.
(300 MHz, DMSO-d6): δ 6.84-6.95 (3H, m, ArH), 6.98-
7.05 (6H, m, ArH), 7.07-7.17 (3H, m, ArH), 7.22-7.40
(10H, m, ArH), 7.51 (1H, t, J 7.1 Hz, ArH), 7.96 (2H, d, J
8.0 Hz, ArH), 8.56 (1H, d, J 8.0 Hz, ArH), 11.81 (1H, s,
NHCO), 12.49 (1H, br s, NH). 13C NMR (DMSO-d6, 75.5
MHz): δ 109.0 (Ar-C), 112.6 (Ar-CH), 115.8 (2 x Ar-CH),
116.1 (2 x Ar-CH), 117.6 (Ar-CH), 121.4 (Ar-CH), 121.7
(Ar-CH), 122.2 (Ar-C), 123.6 (2 x Ar-CH), 125.8 (Ar-C),
7. Vervoort, H. C.; Fenical, W.; Keifer, P. A. J. Nat. Prod.
1999, 62, 389-391.

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reductive
cyclisation
of
2-cyano-
arylideneanilines.21 This approach has been used in an
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