A rapid and efficient synthesis of benzimidazoles using hypervalent iodine as oxidant

Article abstract of DOI:10.1055/s-2007-965922

Various 2-arylbenzimidazoles were synthesized from phenylenediamines and aldehydes via a one-step process using hypervalent iodine as an oxidant. The salient features of this method include mild conditions, short reaction times (3-5 min), high yields, and simple procedure. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-965922

PAPER
675
A Rapid and Efficient Synthesis of Benzimidazoles Using Hypervalent Iodine
as Oxidant
S
ynthesisof Be
i
nzimid
-
azoles Hua Du, Yan-Guang Wang*
Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. of China
Fax +86(571)87951512; E-mail: orgwyg@zju.edu.cn
Received 16 October 2006; revised 5 December 2006
tuted with electron-donating groups and ortho-substituted
aldehydes gave poor yields.18
Abstract: Various 2-arylbenzimidazoles were synthesized from
phenylenediamines and aldehydes via a one-step process using hy-
pervalent iodine as an oxidant. The salient features of this method
include mild conditions, short reaction times (3–5 min), high yields,
and simple procedure.
Iodobenzene diacetate (IBD) as a general oxidizing re-
agent has been well demonstrated.19 Using iodine(III) re-
agents, oxidative rearrangement and cyclization of N-
substituted amidines to the synthesis of benzimidazoles
were reported in 1997,20 but in this article, the synthesis of
benzimidazoles was influenced by amidine substituents
and the leaving group. Jung and co-workers21 also report-
ed an approach to 2-pyridin-3-ylbenzimidazoles by con-
densation of 3-pyridinecarboxaldehyde with substituted
1,2-phenylenediamines following oxidative cyclization
with IBD. As an improvement of this method, we herein
report a rapid and general procedure for the construction
of 2-substituted benzimidazoles using IBD as an oxidant.
Key words: benzimidazoles, iodobenzene diacetate (IBD), oxida-
tions, o-phenylenediamines
Benzimidazoles are very useful building blocks for the de-
velopment of molecules that are important in medicinal
chemistry. Substituted benzimidazole derivatives have
found applications as diverse therapeutic agents, includ-
ing antiulcers, antihypertensives, antivirals, antifungals,
anticancers, and antihistaminics.1–3 Because of their im-
portance, the synthesis of substituted benzimidazoles has
become a focus of synthetic organic chemistry. There are
two general methods for the synthesis of 2-substituted
benzimidazoles. One is the coupling of phenylenedi-
The selected model reaction was carried out with o-phe-
nylenediamine (1a) (1.0 mmol) and benzaldehyde (2a)
(1.0 mmol) and IBD (1.5 mmol) at room temperature
(Table 1). We surprisingly found that the reaction was
very rapid (3–5 min) to afford 2-phenylbenzimidazole
(3a). Several organic solvents were tested (Table 1, en-
tries 1–7), and 1,4-dioxane gave the best yield (Table 1,
entry 4). Increasing the amount of IBD did not give better
yield (Table 1, entry 8), while decreasing the amount of
IBD resulted in a significant reduction of the yield
(Table 1, entries 9–12). It is interesting that 83% yield was
obtained even under solvent-free conditions (Table 1, en-
try 13).
4
amines with carboxylic acids or their derivatives (ni-
triles, imidates, or orthoesters),5 which often requires
strong acidic conditions, and sometimes combines with
very high temperature, or the use of microwave irradia-
tion.6 The other involves a two-step procedure that in-
cludes the oxidative cyclo-dehydrogenation of aniline
Schiff bases, which are often generated in situ from the
condensation of phenylenediamines and aldehydes. Vari-
ous oxidative reagents, such as nitrobenzene (high-boiling
oxidant/solvent),7 1,4-benzoquinone,8 DDQ,9 tetracyano-
ethylene,10 benzofuroxan,11 MnO2,12 Pb(OAc)4,13 Ox-
one,14 NaHSO3,15 and Na2S2O5,16 have been employed in
the two-step procedures. Partially because of the avail-
ability of a vast number of aldehydes, the two-step method
has been extensively used. However, most of these proce-
dures produce toxic or environmentally problematic by-
products, often require laborious workup and purifica-
tions (i.e., to remove quinones and related products), and/
or suffer from low isolation yields. Recently, Lin and co-
workers17 reported a synthesis of benzimidazoles using
oxygen as an oxidant. However, the reaction required a
high temperature (100 °C) and a prolonged reaction time
(~28 h). The I2/KI/K2CO3/H2O system was also developed
for the synthesis of benzimidazoles, but aldehydes substi-
To test the generality and versatility of this procedure in
the synthesis of substituted benzimidazoles, we examined
a number of substituted phenylenediamines 1 and aromat-
ic aldehydes 2 using the optimized conditions (Table 2).
As shown in Table 2, both electron-rich and electron-
deficient benzaldehydes gave 2-aryl-benzimidazoles in
good to excellent yields (Table 2, entries 1–13). Heteroar-
yl aldehydes such as 2-furyl, 2-thiophene, 2-pyrrolyl, and
2-pyridinylcarboxaldehydes also gave good yields
(Table 2, entries 14–17). It is noteworthy that the reac-
tions were complete in about 3–5 minutes in all cases.
Mechanistically, a plausible pathway for the formation of
benzimidazoles involves the formation of intermediate
Schiff’s bases A, which reacted with IBD to form the cy-
clic adduct B by intramolecular participation of o-amino
group. The elimination of iodobenzene and acetic acid af-
forded the 2-aryl-benzimidazoles (Scheme 1). In our reac-
tion, the resulting iodobenzene was determined by GC/
MS.
SYNTHESIS 2007, No. 5, pp 0675–0678
x
x
.
x
x
.2
0
0
7
Advanced online publication: 08.02.2007
DOI: 10.1055/s-2007-965922; Art ID: F17506SS
© Georg Thieme Verlag Stuttgart · New York

676
L.-H. Du, Y.-G. Wang
PAPER
Table 2 Synthesis of 2-Arylbenzimidazoles 3
Table 1 Effects of Solvent and IBD on the Reaction between
o-Phenylenediamine and Benzaldehyde
N
NH2
O
1.5 equiv IBD
R
Ar
O
R
+
dioxane
r.t., 3–5 min
H
Ar
N
H
NH2
N
NH2
IBD
H
+
r.t., 3–5 min
1
2
3
N
H
NH2
1a
2a
3a
Entry
R
Ar
Ph
Time
(min)
Product
Yield
(%)a
Entry
1
Solvent
MeOH
EtOH
IBD (mmol)
1.5
Yield (%)a
1
2
H
3
3
3
5
3a
3b
3c
3d
3e
3f
98
92
90
86
85
84
94
90
82
83
90
85
83
87
88
85
86
83
85
84
98
89
78
81
97
85
80
75
68
83
H
4-ClC6H4
2-ClC6H4
4-EtC6H4
2
1.5
3
H
3
MeCN
1.5
4
H
4
dioxane
DMF
1.5
5
H
4-MeOC6H4
2-MeOC6H4
4-BrC6H4
4-FC6H4
4-t-BuC6H4
2-MeC6H4
4-ClC6H4
Ph
5
5
3
3
5
5
5
5
5
3
3
3
3
5
1.5
6
H
6
CH2Cl2
THF
1.5
7
H
3g
3h
3i
7
1.5
8
H
8
dioxane
dioxane
dioxane
dioxane
dioxane
none
1.6
9
H
9
1.2
10
11
12
13
14
15
16
17
H
3j
10
11
12
13
1.0
Me
Me
MeO
H
3k
3l
0.8
0.5
Ph
3m
3n
3o
3p
3q
1.5
2-furyl
a Isolated yield.
H
2-thienyl
2-pyrrolyl
2-pyridyl
H
NH2
..
NH2
O
H
R
R
+
H
Ar
NH2
N
Ar
a Isolated yield.
A
Ph
I OAc
OAc
All chemicals were obtained from commercial suppliers and used
without further purification. Melting points are uncorrected. Flash
column chromatography was carried out on 300–400 mesh silica
gel. IR spectra were recorded on a PerkinElmer 983 FT-IR spec-
trometer. 1H NMR spectra were recorded on a Bruker Avance DMX
500 or 400 MHz instrument. GC-MS analyses were performed on a
HP-5973 spectrometer.
PhI
AcOH
AcOH
R
H
N
N
Ar
H
R
Ar
N
I
N
H
Ph
OAc
B
2-Arylbenzimidazoles 3; General Procedure
Scheme 1
To a solution of o-phenylenediamine 1 (108 mg, 1.0 mmol) and al-
dehyde 2 (1.0 mmol) in 1,4-dioxane (5 mL), was added iodoben-
zene diacetate (483 mg, 1.5 mmol). The mixture was well stirred at
r.t. for 3–5 min, and then concentrated in vacuo. The residue was
purified by silica gel column chromatography with EtOAc–hexane
(1:6) to afford pure benzimidazole 3 (Table 2).
In summary, we have developed a general and efficient
one-pot synthesis of 2-arylbenzimidazoles from phen-
ylenediamines and aromatic aldehydes using iodobenzene
diacetate as an oxidant. The mild reaction conditions, the
fast reaction times (3–5 min), the high yields as well as the
generality make our methodology a valid contribution to
the existing processes in the field of benzimidazole deriv-
atives synthesis. The synthetic applications of this method
are under investigation.
2-Phenylbenzimidazole (3a)
Mp 289–291 °C (Lit.22 mp 292 °C).
IR (KBr): 1621 (C=N), 3447 cm–1 (NH).
1H NMR (400 MHz, DMSO-d6): d = 12.93 (s, 1 H), 7.92 (d, J = 1.3
Hz, 2 H), 7.47 (m, 1 H), 7.22 (m, 4 H), 6.95 (m, 2 H).
MS (EI): m/z (%) = 194 (100, [M+]), 192 (25), 167 (8), 97 (10).
Synthesis 2007, No. 5, 675–678 © Thieme Stuttgart · New York

PAPER
Synthesis of Benzimidazoles
677
2-(4-Chlorophenyl)benzimidazole (3b)
Mp 292–294 °C (Lit.22 mp 294 °C).
2-(4-tert-Butylphenyl)benzimidazole (3i)
Mp 257–258 °C (Lit.26 mp 258 °C).
IR (KBr): 1624 (C=N), 3447 cm–1 (NH).
IR (KBr): 1626 (C=N), 3447 cm–1 (NH).
1H NMR (500 MHz, CDCl3): d = 12.93 (s, 1 H), 8.02 (d, J = 8.45
Hz, 2 H), 7.67 (t, J = 2.88 Hz, 2 H), 7.43 (d, J = 8.4 Hz, 2 H), 7.31
(q, J = 3.05 Hz, 2 H).
1H NMR (500 MHz, CDCl3): d = 12.98 (s, 1 H), 8.02 (d, J = 8.42
Hz, 2 H), 7.66 (d, J = 9.06 Hz, 2 H), 7.50 (d, J = 8.44 Hz, 2 H), 1.35
(s, 9 H).
MS (EI): m/z (%) = 228 (100, [M+]), 230 (20), 229 (15), 174 (25),
114 (9).
MS (EI): m/z (%) = 250 (100, [M+]), 251 (18), 192 (10).
2-(2-Methylphenyl)benzimidazole (3j)
Mp 199–200 °C (Lit.23 mp 198–200 °C).
2-(2-Chlorophenyl)benzimidazole (3c)
Mp 233–234 °C (Lit.22 mp 234 °C).
IR (KBr): 1624 (C=N), 3447 cm–1 (NH).
IR (KBr): 1620 (C=N), 3447 cm–1 (NH).
1H NMR (400 MHz, DMSO-d6): d = 12.81 (s, 1 H), 7.67–7.63 (m,
3 H), 7.37–7.27 (m, 5 H), 2.60 (s, 3 H).
1H NMR (500 MHz, CDCl3): d = 12.93 (s, 1 H), 8.44 (q, J = 3.10
Hz, 1 H), 7.71 (s, 2 H), 7.50 (t, J = 3.8 Hz, 1 H), 7.42 (m, 2 H), 7.33
(q, J = 3.05 Hz, 2 H).
MS (EI): m/z (%) = 208 (100, [M+]), 209 (25), 181 (40), 112 (10).
MS (EI): m/z (%) = 228 (100, [M+]), 230 (21), 229 (14), 174 (23),
114 (9).
2-(4-Chlorophenyl)-5-methylbenzimidazole (3k)
Mp 224–225 °C (Lit.25 mp 224 °C).
IR (KBr): 1621 (C=N), 3447 cm–1 (NH).
2-(4-Ethylphenyl)benzimidazole (3d)
Mp 143–145 °C (Lit.22 mp 145 °C).
1H NMR (500 MHz, CDCl3): d = 12.81 (s, 1 H), 8.02 (d, J = 8.45
Hz, 2 H), 7.67 (m, 4 H), 7.21 (d, J = 3.05 Hz, 1 H), 2.41 (s, 3 H).
IR (KBr): 1620 (C=N), 3447 cm–1 (NH).
MS (EI): m/z (%) = 242 (100, [M+]), 244 (25), 229 (14).
1H NMR (400 MHz, DMSO-d6): d = 12.80 (s, 1 H), 8.09 (d,
J = 8.40 Hz, 2 H), 7.64 (d, J = 8.80 Hz, 1 H), 7.51 (d, J = 8.4 Hz, 1
H), 7.39 (d, J = 8.00 Hz, 2 H), 7.18 (m, 2 H), 2.68 (d, J = 7.60 Hz,
2 H), 1.23 (t, J = 7.80 Hz, 3 H).
5-Methyl-2-phenylbenzimidazole (3l)
Mp 242–243 °C (Lit.26 mp 242–243 °C).
IR (KBr): 1623 (C=N), 3447 cm–1 (NH).
MS (EI): m/z (%) = 222 (100, [M+]), 223 (20), 207 (85), 103 (25).
1H NMR (500 MHz, CDCl3): d = 12.72 (s, 1 H), 8.12 (d, J = 7.51
Hz, 2 H), 7.48 (m, 4 H), 7.35 (s, 1 H), 7.01 (d, J = 8.1 Hz, 1 H), 2.40
(s, 3 H).
2-(4-Methoxyphenyl)benzimidazole (3e)
Mp 224–226 °C (Lit.22 mp 226 °C).
MS (EI): m/z (%) = 208 (100, [M+]), 209 (15), 129 (14).
IR (KBr): 1624 (C=N), 3447 cm–1 (NH).
1H NMR (400 MHz, DMSO-d6): d = 12.72 (s, 1 H), 8.11 (d,
J = 8.80 Hz, 2 H), 7.61 (d, J = 7.60 Hz, 1 H), 7.49 (d, J = 6.80 Hz,
1 H), 7.14 (m, 4 H), 3.84 (s, 3 H).
5-Methoxy-2-phenylbenzimidazole (3m)
Mp 143–145 °C (Lit.26 mp 143–144 °C).
IR (KBr): 1624 (C=N), 3447 cm–1 (NH).
MS (EI): m/z (%) = 224 (100, [M+]), 225 (20), 209 (45), 181 (40),
112 (10).
1H NMR (400 MHz, DMSO-d6): d = 12.72 (s, 1 H), 8.10 (d,
J = 8.01 Hz, 2 H), 7.45 (m, 4 H), 7.10 (s, 1 H), 6.82 (dd, J = 8.71,
2.01 Hz, 1 H), 3.78 (s, 3 H).
2-(2-Methoxyphenyl)benzimidazole (3f)
Mp 157–158 °C (Lit.23 mp 155–158 °C).
MS (EI): m/z (%) = 224 (100, [M+]), 225 (15), 207 (10), 103 (25).
IR (KBr): 1624 (C=N), 3447 cm–1 (NH).
2-(2-Furyl)benzimidazole (3n)
Mp 287–288 °C (Lit.22 mp 288 °C).
1H NMR (400 MHz, DMSO-d6): d = 12.11 (s, 1 H), 8.32 (m, 1 H),
7.62 (m, 2 H), 7.48 (m, 1 H), 7.18 (m, 4 H), 4.03 (s, 3 H).
IR (KBr): 1627 (C=N), 3447 cm–1 (NH).
MS (EI): m/z (%) = 224 (100, [M+]), 225 (20), 209 (45), 181 (40),
112 (10).
1H NMR (400 MHz, DMSO-d6): d = 12.91 (s, 1 H), 7.94 (d,
J = 1.20 Hz, 1 H), 7.55 (d, J = 1.50 Hz, 2H), 7.21–7.19 (m, 3 H),
6.74–6.72 (m, 1 H).
2-(4-Bromophenyl)benzimidazole (3g)
Mp 299–300 °C (Lit.14 mp 300 °C).
MS (EI): m/z (%) = 184 (100, [M+]), 185 (10), 155 (20), 129 (9).
IR (KBr): 1623 (C=N), 3447 cm–1 (NH).
2-(2-Thienyl)benzimidazole (3o)
Mp 330–332 °C (Lit.18 mp 330 °C).
1H NMR (500 MHz, DMSO-d6): d = 12.98 (s, 1 H), 8.11 (d,
J = 8.50 Hz, 2 H), 7.77 (d, J = 8.50 Hz, 2 H), 7.66 (s, 1 H), 7.54 (s,
1 H), 7.21 (s, 2 H).
IR (KBr): 1621 (C=N), 3447 cm–1 (NH).
1H NMR (400 MHz, DMSO-d6): d = 12.93 (s, 1 H), 7.82 (d, J = 2.6
Hz, 1 H), 7.73 (d, J = 3.2 Hz, 1 H), 7.58–7.51 (m, 2 H), 7.24–7.18
(m, 3 H).
MS (EI): m/z (%) = 272 (100, [M+]), 274 (90), 273 (10).
2-(4-Fluorophenyl)benzimidazole (3h)
Mp 250–251 °C (Lit.24 mp 247–248 °C).
MS (EI): m/z (%) = 200 (100, [M+]), 174 (10), 156 (15), 100 (10).
IR (KBr): 1624 (C=N), 3447 cm–1 (NH).
2-(2-Pyrrolyl)benzimidazole (3p)
Mp 273–275 °C (Lit.27 mp 274–275 °C).
1H NMR (500 MHz, CDCl3): d = 12.98 (s, 1 H), 8.04 (m, 2 H), 7.29
(m, 4 H), 7.19 (m, 2 H).
IR (KBr): 1624 (C=N), 3447 cm–1 (NH).
MS (EI): m/z (%) = 212 (100, [M+]), 211 (20), 213 (15).
Synthesis 2007, No. 5, 675–678 © Thieme Stuttgart · New York

678
L.-H. Du, Y.-G. Wang
PAPER
(6) (a) Bourgrin, K.; Loupy, A.; Soufiaoui, M. Tetrahedron
1H NMR (500 MHz, DMSO-d6): d = 12.91 (s, 1 H), 7.61 (d,
J = 1.61 Hz, 2 H), 7.20 (d, J = 1.53 Hz, 2 H), 6.52 (d, J = 1.50 Hz,
1 H), 6.05 (m, 2 H).
1998, 54, 8055. (b) Reddy, G. V.; Rao, V. V. V. N. S. R.;
Narsaiah, B.; Rao, P. S. Synth. Commun. 2002, 32, 2467.
(c) Ben-Alloum, A.; Bakkas, S.; Soufiaoui, M. Tetrahedron
Lett. 1998, 39, 4481.
MS (EI): m/z (%) = 183 (100, [M+]), 184 (11), 114 (25), 100 (5).
(7) (a) Dubey, P. K.; Ratnam, C. V. Indian J. Chem., Sect. B:
Org. Chem. Incl. Med. Chem. 1979, 18, 428. (b) Yadagiri,
B.; Lown, J. W. Synth. Commun. 1990, 20, 955. (c)Bathini,
Y.; Rao, K. E.; Shea, R. G.; Lown, J. W. Chem. Res. Toxicol.
1990, 3, 268. (d) Singh, M. P.; Joseph, T.; Kumar, S.;
Bathini, Y.; Lown, J. W. Chem. Res. Toxicol. 1992, 5, 597.
(e) Harapanhalli, R. S.; McLaughlin, L. W.; Howell, R. W.;
Rao, D. V.; Adelstein, S. J.; Kassis, A. I. J. Med. Chem.
1996, 39, 4804.
2-(2-Pyridyl)benzimidazole (3q)
Mp 218–219 °C (Lit.22 mp 218 °C).
IR (KBr): 1624 (C=N), 3447 cm–1 (NH).
1H NMR (500 MHz, DMSO-d6): d = 12.91 (s, 1 H), 8.48 (d,
J = 1.44 Hz, 1 H), 7.71 (m, 4 H), 7.35 (m, 1 H), 7.21 (d, J = 1.49
Hz, 2 H).
MS (EI): m/z (%) = 195 (M+, 100), 196 (11), 145 (15), 123 (9).
(8) (a) Verner, E.; Katz, B. A.; Spencer, J. R.; Allen, D.; Hataye,
J.; Hruzewicz, W.; Hui, H. C.; Kolesnikov, A.; Li, Y.;
Luong, C.; Martelli, A.; Radika, K.; Rai, R.; She, M.;
Shrader, W.; Sprengeler, P. A.; Trapp, S.; Wang, J.; Young,
W. B.; Mackman, R. L. J. Med. Chem. 2001, 44, 2753.
(b) Kumar, S.; Kansal, V.; Bhaduri, A. Indian J. Chem., Sect.
B: Org. Chem. Incl. Med. Chem. 1991, 20, 254.
(9) (a) vanden Eynde, J. J.; Delfosse, F.; Lor, P.; van Haverbeke,
Y. Tetrahedron 1995, 51, 5813. (b) Lee, K. J.; Janda, K. D.
Can. J. Chem. 2001, 79, 1556.
Acknowledgment
We thank the Specialized Research Fund for Doctoral Program of
Higher Education (20050335101), the Natural Science Foundation
of Zhejiang Province (R404109), as well as the Teaching and Re-
search Award Program for Outstanding Young Teachers in Higher
Education Institutions of MOE, P.R.C.
References
(10) Chikashita, H.; Nishida, S.; Miyazaki, M.; Morita, Y.; Itoh,
K. Bull. Chem. Soc. Jpn. 1987, 60, 737.
(1) (a) Erhardt, P. W. J. Med. Chem. 1987, 30, 231.
(b) Tomczuk, B. E.; Taylor, C. R. Jr.; Moses, L. M.;
Sutherland, D. B.; Lo, Y. S.; Johnson, D. N.; Kinnier, W. B.;
Kilpatrick, B. F. J. Med. Chem. 1991, 34, 2993. (c) Spasov,
A. A.; Yozhitsa, I. N.; Bugaeva, L. I.; Anisimova, V. A.
Pharm. Chem. J. 1999, 33, 232. (d) Preston, P. N. Chem.
Heterocycl. Compd. 1980, 40, 531. (e) Zimmer, C.;
Wahnert, U. Prog. Biophys. Mol. Biol. 1986, 47, 31.
(f) Gravatt, G. L.; Baguley, B. C.; Wilson, W. R.; Denny, W.
A. J. Med. Chem. 1994, 37, 4338. (g) Soderlind, K.-J.;
Gorodetsky, B.; Singh, A. K.; Bachur, N.; Miller, G. G.;
Lown, J. W. Anti-Cancer Drug Des. 1999, 14, 19.
(2) (a) Kim, J. S.; Gatto, B.; Yu, C.; Liu, A.; Liu, L. F.; LaVoie,
E. J. J. Med. Chem. 1996, 39, 992. (b) Chen, A. Y.; Yu, C.;
Gatto, B.; Liu, L. F. Proc. Natl. Acad. Sci. U.S.A. 1993, 90,
8131. (c) Woynarowski, J. M.; McHugh, M. M.; Sigmud, R.
D.; Beerman, T. A. Mol. Pharmacol. 1989, 35, 177.
(3) Roth, T.; Morningstar, M. L.; Boyer, P. L.; Hughes, S. H.;
Buckheit, R. W. Jr.; Michejda, C. J. J. Med. Chem. 1997, 40,
4199.
(4) (a) Grimmet, M. R. In Comprehensive Heterocyclic
Chemistry, Vol. 5; Katritzky, A. R.; Rees, C. W., Eds.;
Pergamon Press: Oxford, 1984, 457. (b) Wright, J. B. Chem.
Rev. 1951, 48, 397. (c) Middleton, R. W.; Wibberley, D. G.
J. Heterocycl. Chem. 1980, 17, 1757. (d) Hisano, T.;
Ichikawa, M.; Tsumoto, K.; Tasaki, M. Chem. Pharm. Bull.
1982, 30, 2996. (e) Geratz, J. D.; Stevens, F. M.; Polakoski,
K. L.; Parrish, R. F. Arch. Biochem. Biophys. 1979, 197, 551.
(5) (a) Czarny, A.; Wilson, W. D.; Boykin, D. W. J. Heterocycl.
Chem. 1996, 33, 1393. (b) Tidwell, R. R.; Geratz, J. D.;
Dann, O.; Volz, G.; Zeh, D.; Loewe, H. J. Med. Chem. 1978,
21, 613. (c) Fairley, T. A.; Tidwell, R. R.; Donkor, I.;
Naiman, N. A.; Ohemeng, K. A.; Lombardy, R. J.; Bentley,
J. A.; Cory, M. J. Med. Chem. 1993, 36, 1746.
(11) Patzold, F.; Zeuner, F.; Heyer, T. H.; Niclas, H. J. Synth.
Commun. 1992, 22, 281.
(12) Bhatnagar, I.; George, M. V. Tetrahedron 1968, 24, 1293.
(13) Stephens, F. F.; Bower, J. D. J. Chem. Soc. 1949, 2971.
(14) Beaulieu, P. L.; Haché, B.; von Moos, E. Synthesis 2003,
1683.
(15) (a) Weidner-Wells, M. A.; Ohemeng, K. A.; Nguyen, V. N.;
Fraga-Spano, S.; Macielag, M. J.; Werblood, H. M.; Foleno,
B. D.; Webb, G. C.; Barrett, J. F.; Hlasta, D. J. Bioorg. Med.
Chem. Lett. 2001, 11, 1545. (b) Austen, S. C.; Kane, J. M. J.
Heterocycl. Chem. 2001, 38, 979.
(16) Lombardy, R. L.; Tanious, F. A.; Ramachandran, K.;
Tidwell, R. R.; Wilson, W. D. J. Med. Chem. 1996, 39, 1452.
(17) Lin, S.; Yang, L. Tetrahedron Lett. 2005, 46, 4315.
(18) Gogoi, P.; Konwar, D. Tetrahedron Lett. 2006, 47, 79.
(19) (a) Stang, P. J.; Zhdankin, V. V. Chem. Rev. 1996, 1123.
(b) Togo, H.; Harda, Y.; Yokoyama, M. J. Org. Chem. 2000,
65, 926. (c) Ohno, M.; Oguri, I.; Eguchi, S. J. Org. Chem.
1999, 64, 8995. (d) Adam, W.; Hajra, S.; Herderich, M.;
Saha-Moeller, C. R. Org. Lett. 2000, 2, 2773. (e) Braun, N.
A.; Ousmer, M.; Bray, J. D.; Bouchu, D.; Peters, K.; Peters,
E.-M.; Ciufolini, M. A. J. Org. Chem. 2000, 65, 4397.
(f) Chen, D. W.; Chen, Z. C. Tetrahedron Lett. 1994, 35,
7637. (g) Varma, R. S.; Saini, R. K.; Prakash, O.
Tetrahedron Lett. 1997, 38, 2621.
(20) Ramsden, C. A.; Rose, H. L. J. Chem. Soc., Perkin Trans. 1
1997, 2319.
(21) Jung, M. H.; Park, J. M.; Lee, I. Y. C.; Ahn, M. J.
Heterocycl. Chem. 2003, 40, 37.
(22) Abdelkrim, B. A. Tetrahedron Lett. 2003, 44, 5935.
(23) Speier, G. J. Org. Chem. 1986, 51, 218.
(24) Bougrin, K.; Loupy, A.; Soufiaoui, M. Tetrahedron 1998,
54, 8055.
(25) Cohen, V. I. J. Heterocycl. Chem. 1979, 16, 13.
(26) Perry, R. J.; Wilson, B. D. J. Org. Chem. 1993, 58, 7016.
(27) George, B.; Papadopoulos, E. P. J. Org. Chem. 1977, 42,
441.
Synthesis 2007, No. 5, 675–678 © Thieme Stuttgart · New York