Furan ring-opening/indole ring-closure: Pictet-spengler-like reaction of 2-(o-aminophenyl)furans with aldehydes

Article abstract of DOI:10.1002/ejoc.200901241

A new simple approach to 3-(2-acylvinyl)-2-(hetero)arylindoles has been developed. The method is based on the acid-catalysed interaction of 2-(2-aminophenyl)furans with (hetero)aromatic aldehydes. The reactions proceed under very mild conditions and lead to indoles containing a reactive α,β-unsaturated ketone moiety, which is suitable for further transformations, in moderate to good yields.

Full text of DOI:10.1002/ejoc.200901241

FULL PAPER
DOI: 10.1002/ejoc.200901241
Furan Ring-Opening/Indole Ring-Closure: Pictet–Spengler-Like Reaction of
2-(o-Aminophenyl)furans with Aldehydes
Alexander V. Butin,*[a] Maxim G. Uchuskin,[a] Arkady S. Pilipenko,[a]
Fatima A. Tsiunchik,[a] Dmitry A. Cheshkov,[b] and Igor V. Trushkov[c]
Keywords: Aldehydes / Cyclization / Pictet–Spengler reaction / Synthetic methods / Heterocycles
A new simple approach to 3-(2-acylvinyl)-2-(hetero)aryl-
indoles has been developed. The method is based on the
acid-catalysed interaction of 2-(2-aminophenyl)furans with
(hetero)aromatic aldehydes. The reactions proceed under
very mild conditions and lead to indoles containing a reactive
α,β-unsaturated ketone moiety, which is suitable for further
transformations, in moderate to good yields.
clude the radical cyclization of N-(o-vinylaryl)-thioamides
(path c)[8] or aryl isocyanides (path d),[9] transition-metal-
catalysed interaction of a double or triple bond with ortho-
isocyanide or imine groups (path e),[10] intramolecular car-
bene insertion into the C–H bond of N-alkylanilines (path
f),[11] ring-closing metathesis (path g)[12] and the McMurry
reaction (path h)[13] among others.[14]
Introduction
For many years indoles have attracted unremitting atten-
tion due to the broad range of their biological activity.[1]
The numerous methods for indole synthesis have been dis-
cussed in multiple publications and summarized in a
number of books and reviews.[2] However, the preparation
of 2,3-disubstituted indoles is a challenge to organic chem-
ists, at least those indoles with substituents at the 2- and/or
3-positions that have reactive functional groups suitable for
further transformations. The synthesis of indoles by the for-
mation of the C2–C3 bond is a promising approach to the
solution of this problem. The first of these syntheses was
realized in 1886 when indole was obtained by the distil-
lation of N-acetyl-o-toluidine in the presence of zinc dust.[3]
This method is not preparative, however; Madelung later
demonstrated that the same transformation can be realized
by heating o-alkylanilides with a base at 400 °C.[4] For a
long time the Madelung reaction (path a in Scheme 1) was
the main route to the indole unit by C2–C3 bond formation
in spite of the incompatibility of many functional groups to
strong basic conditions.[5] An analogous cyclization reac-
tion proceeded when a benzylic carbanion was generated in
the ortho position to an imine or isocyanide group.[6] De-
protonation of N-alkylanilines bearing an ortho substituent
with an electrophilic α-carbon atom (Scheme 1, path b)
leads to indoles by a similar mechanism.[7] Other methods
for the synthesis of indoles by C2–C3 bond formation in-
Scheme 1.
However, a few reports describing the acid-catalysed C2–
C3 bond formation of indoles have been published.[15] The
electrophilic N=C+ or N–C+ moieties are usually the key
intermediates in these reactions.
Similarly, the Pictet–Spengler reaction and related pro-
cesses proceed through the formation of iminium ions. This
stimulated us to design a new approach to 2-arylindoles
bearing a 2-acylvinyl substituent at the C3 atom based on
the recyclization of 2-(2-aminophenyl)furans[15f] under
[a] Research Institute of Heterocyclic Chemistry, Kuban State
Technological University,
2 Moskovskaya st., Krasnodar 350072, Russian Federation
[b] State Scientific Research Institute of Chemistry and Technology
of Organoelement Compounds,
38 Entuziastov St., Moscow 111123, Russian Federation
[c] Department of Chemistry, M. V. Lomonosov Moscow State
University,
Leninskie gory 1/3, Moscow 119991, Russian Federation
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200901241.
920
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 920–926

Furan Ring-Opening/Indole Ring-Closure
Pictet–Spengler-like conditions. These compounds are Table 1. Optimization of the reaction conditions for the model re-
action of the Pictet–Spengler-like indole synthesis by the interac-
tion of 1a with 2a.
interesting both in themselves and as precursors to other
indoles (in the first place, by the modification of the α,β-
unsaturated ketone moiety) with a broad range of biological
activity. Herein we describe this new method of indole gen-
eration by C2–C3 bond formation. In contrast, the forma-
tion of the N–C2 bond is a key step in the previous furan-
to-indole recyclizations.[16]
Results and Discussion
Entry Solvent
Acid
T [°C] Time
Yield [%][a]
We first screened the reaction conditions for the model
reaction between 2-(5-methylfuran-2-yl)aniline (1a) and
benzaldehyde (2a). We found that the target indole 3a was
formed by heating at reflux a benzene solution of the start-
ing compounds with weak Brønsted acids such as Am-
berlyst-15 or CCl3CO2H. However, the yield of 3a was low
under these conditions. Thus, we tried to use acidic systems
that had been found to be effective in other furan recycliza-
tions: HClO4 in dioxane,[16e] HCl(g) in EtOH,[16f] aq. HCl/
AcOH[16h] and TsOH/C6H6.[17] Indeed, we obtained indole
3a in yields of 70–80% by using these acid catalysts. The
product structure was unambiguously proven by X-ray
analysis (Figure 1).[18]
1
2
3
4
5
6
7
8
9
C6H6
C6H6
C6H6
C6H6
C6H6
dioxane
dioxane
EtOH
EtOH
AcOH
AcOH
Amberlyst-15 reflux
24 h
8 h
8 h
20
15
20
77
79
15
72
76
70
78
74
Cl3CCOOH
TsOH·H2O
TsOH
reflux
reflux
reflux 9 min
30–35
30–35
reflux 1 min
30–35 1.5 h
reflux 3 min
30–35 1.5 h
reflux 1 min
TsOH
18 h
24 h
HClO4
HClO4
HCl
HCl
10
11
aq. HCl
aq. HCl
[a] Isolated yields.
A broad range of 2,3-disubstituted and 2,3,6-trisubsti-
tuted indoles were synthesized in 53–79% isolated yields
from various 2-furylanilines and substituted benzaldehydes
(Table 2) under the optimized reaction conditions (aq. HCl/
AcOH, 30–35 °C).
Table 2. Synthesis of 3-(2-acylvinyl)-2-arylindoles 3 from 2-(2-
furyl)anilines 1 and benzaldehydes 2.
Figure 1. Single-crystal X-ray structure of 3a.
The systems HCl(g)/EtOH and aq. HCl/AcOH were
found to be effective both under reflux and at room tem-
perature. The full conversion of the starting furan was
found to proceed after only 1–3 min at reflux. An increase
in the reaction time led to a decrease in the yield due to the
formation of a tar. In contrast, at room temperature the
reaction proceeded to completion after 18–24 h. Heating at
30–35 °C can be considered a good compromise between
these two limits as a similar yield can be obtained after
1.5 h. A good yield was also obtained when the reaction
was performed with anhydrous p-TsOH in C6H6. The use
of TsOH·H2O led, however, to a complex mixture of prod-
ucts. The results of the experiments performed to optimize
the reaction conditions are summarized in Table 1.
Entry Product
X
R
Y
Yield [%][a]
1
2
3
4
5
6
7
8
9
10
11
12
13
3a
3b
3c
3d
3e
3f
H
H
H
H
H
H
H
H
Me
Me
Me
Cl
Cl
Me
Me
Me
Me
Me
Me
Et
H
78
72
70
79
62
53
70
66
77
74
60
76
74
3,4-(MeO)2
4-F
4-O2N
3-O2N
2-O2N
2-HO-5-Cl
4-EtO
3,4-(MeO)2
4-Br
4-F
3,4-(MeO)2
4-O2N
3g
3h
3i
Et
Me
Me
Me
Me
Me
3j
3k
3l
3m
[a] Isolated yields.
Eur. J. Org. Chem. 2010, 920–926
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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A. V. Butin et al.
FULL PAPER
The lowest yield was observed with 2-nitrobenzaldehyde Table 3. Synthesis of indoles 3 from 1 and heteroarenecarbal-
dehydes 2.
(2f). This result cannot be explained by only the steric de-
mands of the ortho substituent as 5-chlorosalicylaldehyde
(2g) gave the corresponding indole in 70% yield. Moreover,
the reaction of 2-methoxynaphthalene-1-carbaldehyde (2j)
with 1e led to the indole 3n in 79% yield (Scheme 2).
Entry Product
X
R
Y
R1
Yield [%][a]
1
2
3
4
5
3o
3p
3q
3r
3s
Cl
H
H
Cl
H
Me
Me
Me
Me
Et
O
O
O
S
Me
2,4,6-Cl3C6H2
4-Me-2-O2NC6H3
H
80
75
65
75
43
S
NO2
[a] Isolated yields.
Scheme 2.
In contrast, pyridinecarbaldehydes failed to give the tar-
get indoles in this process. Similarly, acetaldehyde was not
found to be efficient in indole formation under these reac-
tion conditions, possibly due to the reversibility of the for-
mation of imine 4 and, as a result, competitive furan ring-
opening leading to various byproducts.
The possible mechanism of this reaction is given in
Scheme 3. The first step of the process is the formation of
the Schiff base 4. We isolated this intermediate when the
reaction was performed at a lower temperature as well as
when the starting compounds 1 and 2 were mixed in HCl-
free acetic acid. The protonation of 4 yields the acylimi-
nium ion 5, which attacks the C2 atom of the furan ring to
yield the cation 6. Subsequent furan ring-opening leads to
the indole 3.
Conclusions
A few approaches to 2-(hetero)arylindoles bearing an
α,β-unsaturated ketone moiety at the C3 position have pre-
viously been reported, namely, aldol condensation of in-
dole-3-carbaldehyde,[20] palladium-catalysed processes[21]
and Friedel–Crafts-like reactions.[22] We have developed a
new synthetic route to these compounds based on an acid-
catalysed imine formation/indole ring-closure/furan ring-
opening sequence. The synthesized compounds can be fur-
ther modified to give various bioactive compounds by sim-
ple procedures similar to the known transformations of
other 3-(2-acylvinyl)indoles.[23] The optimization of the re-
action conditions for the synthesis of the analogous 3-(2-
acylvinyl)-2-alkylindoles is under investigation.
Experimental Section
Scheme 3.
General: NMR spectra were recorded with a Bruker DPX 300
(300 MHz for 1H and 75 MHz for 13C NMR) spectrometer at room
temperature. The chemical shifts (δ) were measured in ppm with
respect to the solvent (CDCl3: 1H: δ = 7.26 ppm, 13C: δ =
77.13 ppm; [D6]DMSO: 1H: δ = 2.50 ppm, 13C: δ = 39.7 ppm).
Coupling constants (J) are given in Hz. The multiplicities of the
signals are described as follows: s = singlet, d = doublet, t = triplet,
q = quadruplet, m = multiplet, dd = double doublet, br. = broad-
ened. IR spectra were measured as KBr plates with InfraLUM FT-
02 and InfraLUM FT-801 instruments. Mass spectra were recorded
with a Kratos MS-30 instrument with 70 eV electron-impact ion-
ization at 200 °C. Melting points (uncorrected) were determined
in capillaries with an Electrothermal 9100 capillary melting-point
This kind of reactivity is specific to furan derivatives as
it is known that other 2-(heteroaryl)anilines react with alde-
hydes in the presence of acids by the common Pictet–Speng-
ler reaction to form quinoline derivatives annulated to the
corresponding heterocycles.[19]
We next studied the reactivity of heterocyclic aldehydes
and found that furfural and thiophene-2-carbaldehyde de-
rivatives reacted efficiently with 2-(2-furyl)anilines to yield
the corresponding 2-(heteroaryl)indoles in yields of 43–80%
(Table 3).
922
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 920–926

Furan Ring-Opening/Indole Ring-Closure
apparatus. Column chromatography was performed on silica gel
KSK (50–160 µm, LTD Sorbpolymer). The 2-(5-alkylfuran-2-yl)-
anilines 1 were prepared according to published procedures.[15f] All
the reactions were carried out by using freshly distilled and dry
solvents.
General Procedure for the Synthesis of Indoles 3:[24] 2-Furylaniline
1 (3 mmol) and aldehyde 2 (3 mmol) were mixed with a solution of
hydrochloric acid (0.01 mL) in acetic acid (5 mL). The resulting
mixture was stirred at 30–35 °C for 1.5 h, poured into H2O
(200 mL) and neutralized with NaHCO3. The resulting mixture was
extracted with ethyl acetate (3ϫ20 mL). The combined organic
fractions were dried with Na2SO4, treated with activated charcoal
and concentrated under reduced pressure. The residue was purified
by column chromatography on SiO2. Non-polar admixtures were
first removed by using a CH2Cl2/hexane (1:4) mixture followed by
product isolation with acetone as an eluent. Indoles 3 were purified
by recrystallization using the specified solvents.
(75 MHz, [D6]DMSO): δ = 27.9, 110.0, 112.5, 120.9, 121.7, 123.9,
124.0, 124.1 (2 C), 125.7, 130.5 (2 C), 135.8, 137.3, 137.4, 140.4,
147.2, 197.5 ppm. IR (KBr): ν = 3248, 1631, 1602, 1520, 861,
˜
745 cm–1. MS (EI, 70 eV): m/z (%) = 306 (2) [M]+, 217 (26), 109
(11), 63 (17), 43 (100). C18H14N2O3 (306.32): calcd. C 70.58, H
4.61, N 9.15; found C 70.47, H 4.51, N 9.31.
(3E)-4-[2-(3-Nitrophenyl)-1H-indol-3-yl]but-3-en-2-one (3e): Red so-
lid. Yield: 0.57 g, 62%. M.p. 227–228 °C (EtOH/acetone). 1H
3
NMR (300 MHz, [D6]DMSO): δ = 2.29 (s, 3 H, CH3), 6.92 (d, J
= 16.0 Hz, 1 H, =CH), 7.23–7.28 (m, 1 H, HAr), 7.29–7.35 (m, 1
H, HAr), 7.52–7.55 (m, 1 H, HAr), 7.72 (d, 3J = 16.0 Hz, 1 H, =CH),
7.88–7.94 (m, 1 H, HAr), 8.03–8.05 (m, 1 H, HAr), 8.07–8.11 (m, 1
H, HAr), 8.35–8.39 (m, 1 H, HAr), 8.44–8.45 (m, 1 H, HAr), 12.42
(s, 1 H, NH) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 27.8,
109.3, 112.4, 120.8, 121.6, 123.5, 123.6, 123.7, 123.8, 125.6, 130.6,
132.5, 135.8, 135.9, 137.0, 140.4, 148.1, 197.4 ppm. IR (KBr): ν =
˜
3238, 1631, 1610, 1523, 1452, 1349, 1255, 1231, 738 cm–1. MS (EI,
70 eV): m/z (%) = 306 (2) [M]+, 216 (37), 189 (14), 63 (19), 51 (15),
43 (100). C18H14N2O3 (306.32): calcd. C 70.58, H 4.61, N 9.15;
found C 70.64, H 4.56, N 9.27.
(3E)-4-(2-Phenyl-1H-indol-3-yl)but-3-en-2-one (3a): Brown-green
solid. Yield: 0.61 g, 78%. M.p. 224–225 °C (EtOH/acetone). 1H
3
NMR (300 MHz, [D6]DMSO): δ = 2.27 (s, 3 H, CH3), 6.90 (d, J
= 16.2 Hz, 1 H, =CH), 7.21–7.31 (m, 2 H, HAr), 7.49–7.67 (m, 6
(3E)-4-[2-(2-Nitrophenyl)-1H-indol-3-yl]but-3-en-2-one (3f): Red so-
lid. Yield: 0.49 g, 53%. M.p. 251–252 °C (EtOH/acetone). 1H
NMR (300 MHz, [D6]DMSO): δ = 2.20 (s, 3 H, CH3), 6.78 (d, J
H, HAr), 7.77 (d, 3J = 16.2 Hz, 1 H, =CH), 8.01–8.03 (m, 1 H,
Ar), 12.18 (s, 1 H, NH) ppm. 13C NMR (75 MHz, [D6]DMSO):
3
H
= 15.9 Hz, 1 H, =CH), 7.23–7.33 (m, 2 H, HAr), 7.36 (d, 3J =
15.9 Hz, 1 H, =CH), 7.47–7.50 (m, 1 H, HAr), 7.72–7.75 (m, 1 H,
HAr), 7.82–7.87 (m, 1 H, HAr), 7.91–7.97 (m, 1 H, HAr), 8.02–8.05
(m, 1 H, HAr), 8.24–8.27 (m, 1 H, HAr), 12.27 (s, 1 H, NH) ppm.
13C NMR (75 MHz, [D6]DMSO): δ = 28.0, 109.7, 112.3, 120.6,
121.5, 122.3, 123.3, 125.0, 125.2, 125.4, 131.1, 133.6, 133.7, 135.0,
δ = 28.0, 108.3, 112.2, 120.7, 121.4, 122.3, 123.1, 125.8, 129.0 (2
C), 129.1, 129.6 (2 C), 131.1, 136.8, 136.9, 143.9, 197.2 ppm. IR
(KBr): ν = 3215, 1600, 1570, 1451, 1426, 1269, 1231, 776, 738 cm–1.
˜
MS (EI, 70 eV): m/z (%) = 261 (45) [M]+, 246 (45), 218 (100), 217
(62), 189 (17), 108 (16). C18H15NO (261.33): calcd. C 82.73, H 5.79,
N 5.36; found C 82.58, H 5.75, N 5.22.
136.9, 139.3, 149.1, 197.1 ppm. IR (KBr): ν = 3201, 1613, 1524,
˜
(3E)-4-[2-(3,4-Dimethoxyphenyl)-1H-indol-3-yl]but-3-en-2-one (3b):
Yellow solid. Yield: 0.69 g, 72%. M.p. 215–216 °C (EtOH/acetone).
1H NMR (300 MHz, [D6]DMSO): δ = 2.27 (s, 3 H), 3.86 (s, 3 H,
OCH3), 3.87 (s, 3 H, OCH3), 6.85 (d, 3J = 16.2 Hz, 1 H, =CH),
7.14–7.28 (m, 5 H, HAr), 7.47–7.50 (m, 1 H, HAr), 7.83 (d, 3J =
16.2 Hz, 1 H, =CH), 7.96–7.99 (m, 1 H, HAr), 12.06 (s, 1 H, NH)
ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 27.8, 55.6 (2 C), 107.8,
111.9, 112.0, 112.6, 120.5, 121.3, 121.9, 122.4, 122.9, 123.3, 125.9,
1445, 783, 748, 699 cm–1. MS (EI, 70 eV): m/z (%) = 306 (2) [M]+,
218 (20), 76 (20), 63 (22), 51 (20), 43 (100). C18H14N2O3 (306.32):
calcd. C 70.58, H 4.61, N 9.15; found C 70.64, H 4.56, N 9.27.
(1E)-1-[2-(5-Chloro-2-hydroxyphenyl)-1H-indol-3-yl]pent-1-en-3-one
(3g): Brown solid. Yield: 0.68 g, 70%. M.p. 208–209 °C (EtOH/ace-
1
3
tone). H NMR (300 MHz, [D6]DMSO): δ = 1.02 (t, J = 7.4 Hz,
3
3
3 H, CH3), 2.60 (q, J = 7.4 Hz, 2 H, CH2), 6.84 (d, J = 15.9 Hz,
1 H, =CH), 7.08 (d, 3J = 8.7 Hz, 1 H, HAr), 7.18–7.28 (m, 2 H,
HAr), 7.33 (d, 4J = 2.4 Hz, 1 H, HAr), 7.41 (dd, 3J = 8.7, 4J =
136.7, 137.3, 144.2, 148.9, 149.7, 197.2 ppm. IR (KBr): ν = 3306,
˜
1587, 1282, 1247, 1181, 1134, 1021, 975 cm–1. MS (EI, 70 eV): m/z
(%) = 321 (100) [M]+, 306 (20), 290 (32), 278 (68), 263 (77), 247
(90), 233 (27), 45 (18). C20H19NO3 (321.38): calcd. C 74.75, H 5.96,
N 4.36; found C 74.78, H 6.01, N 4.20.
3
2.4 Hz, 1 H, HAr), 7.45–7.48 (m, 1 H, HAr), 7.58 (d, J = 15.9 Hz,
1 H, =CH), 7.99–8.01 (m, 1 H, HAr), 10.33 (s, 1 H, OH), 11.98 (s,
1 H, NH) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 8.5, 33.8,
109.5, 112.1, 117.8, 119.9, 120.2, 120.5, 121.1, 122.4, 122.7, 125.3,
(3E)-4-[2-(4-Fluorophenyl)-1H-indol-3-yl]but-3-en-2-one (3c): Yel-
low solid. Yield: 0.59 g, 70%. M.p. Ͼ250 °C (dec.; EtOH/acetone).
1H NMR (300 MHz, [D6]DMSO): δ = 2.26 (s, 3 H, CH3), 6.87 (d,
3J = 16.0 Hz, 1 H, =CH), 7.19–7.30 (m, 2 H, HAr), 7.43–7.51 (m,
3 H, HAr), 7.63–7.73 (m, 3 H, =CH + HAr), 7.99–8.02 (m, 1 H,
HAr), 12.18 (s, 1 H, NH) ppm. 13C NMR (75 MHz, [D6]DMSO):
130.2, 131.2, 136.1, 136.8, 140.1, 154.5, 199.7 ppm. IR (KBr): ν =
˜
3296, 1611, 1441, 1203, 1181, 749, 727 cm–1. MS (EI, 70 eV): m/z
(%) = 327/325 (1/3) [M]+, 233 (25), 204 (40), 117 (45), 102 (45), 88
(30), 75 (27), 63 (30), 57 (100). C19H16ClNO2 (325.80): calcd. C
70.05, H 4.95, N 4.30; found C 70.31, H 4.94, N 4.28.
2
δ = 27.9, 108.4, 112.2, 116.1 (d, JCF = 21.8 Hz, 2 C), 120.6, 121.4,
(1E)-1-[2-(4-Ethoxyphenyl)-1H-indol-3-yl]pent-1-en-3-one
(3h):
4
3
122.5, 123.1, 125.7, 127.5 (d, JCF = 3.0 Hz), 131.7 (d, JCF
=
Brown solid. Yield: 0.63 g, 66%. M.p. 135–136 °C (EtOH/acetone).
1
8.5 Hz, 2 C), 136.5, 136.7, 142.8, 162.6 (d, JCF = 246.9 Hz),
1H NMR (300 MHz, [D6]DMSO): δ = 1.03 (t, 3J = 7.5 Hz, 3 H,
197.2 ppm. IR (KBr): ν = 3234, 1602, 1572, 1457, 1267, 1232,
˜
3
3
CH3), 1.38 (t, J = 7.1 Hz, 3 H, CH3), 2.62 (q, J = 7.5 Hz, 2 H,
844 cm–1. MS (EI, 70 eV): m/z (%) = 279 (54) [M]+, 264 (68), 236
(100), 118 (18), 43 (18). C18H14FNO (279.32): calcd. C 77.40, H
5.05, N 5.01; found C 77.58, H 4.97, N 5.16.
3
3
CH2), 4.13 (q, J = 7.1 Hz, 2 H, CH2O), 6.90 (d, J = 15.9 Hz, 1
H, =CH), 7.15 (d, 3J = 8.7 Hz, 2 H, HAr), 7.18–7.27 (m, 2 H, HAr),
3
7.45–7.48 (m, 1 H, HAr), 7.53 (d, J = 8.7 Hz, 2 H, HAr), 7.76 (d,
(3E)-4-[2-(4-Nitrophenyl)-1H-indol-3-yl]but-3-en-2-one (3d): Red so-
3J = 15.9 Hz, 1 H, =CH), 7.97–8.00 (m, 1 H, HAr), 12.03 (s, 1 H,
lid. Yield: 0.73 g, 79%. M.p. 257–258 °C (EtOH/acetone). 1H
NH) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 8.5, 14.7, 33.7,
3
NMR (300 MHz, [D6]DMSO): δ = 2.30 (s, 3 H, CH3), 6.94 (d, J 63.3, 107.8, 112.0, 114.9 (2 C), 120.5, 120.7, 121.3, 122.8, 123.2,
= 15.9 Hz, 1 H, =CH), 7.23–7.28 (m, 1 H, HAr), 7.30–7.35 (m, 1
125.9, 130.9 (2 C), 135.9, 136.7, 144.2, 159.3, 199.7 ppm. IR (KBr):
H, HAr), 7.53–7.55 (m, 1 H, HAr), 7.73 (d, 3J = 15.9 Hz, 1 H, =CH),
ν = 3265, 1608, 1573, 1497, 1454, 1279, 1250, 1208, 1201, 1180,
˜
3
7.91 (d, J = 9.0 Hz, 2 H, HAr), 8.04–8.06 (m, 1 H, HAr), 8.45 (d,
1045 cm–1. MS (EI, 70 eV): m/z (%) = 319 (100) [M]+, 291 (25),
3J = 9.0 Hz, 2 H, HAr), 12.40 (s, 1 H, NH) ppm. 13C NMR
290 (76), 262 (71), 233 (59), 206 (41), 205 (52), 204 (94), 59 (21).
Eur. J. Org. Chem. 2010, 920–926
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
923

A. V. Butin et al.
FULL PAPER
C21H21NO2 (319.41): calcd. C 78.97, H 6.63, N 4.39; found C
79.08, H 6.48, N 4.24.
3
3
4
6.92 (d, J = 16.0 Hz, 1 H, =CH), 7.25 (dd, J = 8.7, J = 2.1 Hz,
4
3
1 H, HAr), 7.54 (d, J = 2.1 Hz, 1 H, HAr), 7.67 (d, J = 16.0 Hz,
3
3
1 H, =CH), 7.90 (d, J = 9.0 Hz, 2 H, HAr), 8.07 (d, J = 8.7 Hz,
1 H, HAr), 8.45 (d, 3J = 9.0 Hz, 2 H, HAr), 12.53 (s, 1 H, NH) ppm.
13C NMR (75 MHz, [D6]DMSO): δ = 27.9, 110.0, 111.9, 121.8,
122.3, 124.1 (2 C), 124.4, 124.6, 128.3, 130.4 (2 C), 135.1, 136.9,
(3E)-4-[2-(3,4-Dimethoxyphenyl)-6-methyl-1H-indol-3-yl]but-3-en-2-
one (3i): Yellow solid. Yield: 0.77 g, 77%. M.p. 216–217 °C (EtOH/
acetone). 1H NMR (300 MHz, [D6]DMSO): δ = 2.25 (s, 3 H, CH3),
2.44 (s, 3 H, CH3), 3.85 (s, 3 H, OCH3), 3.86 (s, 3 H, OCH3), 6.80
137.7, 140.9, 147.3, 197.4 ppm. IR (KBr): ν = 3277, 1630, 1606,
˜
3
3
4
(d, J = 15.9 Hz, 1 H, =CH), 7.04 (dd, J = 8.1, J = 1.2 Hz, 1 H,
1515, 1349, 1262, 1231, 857 cm–1. MS (EI, 70 eV): m/z (%) = 342/
340 (1/3) [M]+, 251 (24), 216 (25), 113 (22), 108 (40), 94 (26), 75
(31), 43 (100). C18H13ClN2O3 (340.77): calcd. C 63.44, H 3.85, N
8.22; found C 63.32, H 3.71, N 8.27.
3
HAr), 7.12–7.26 (m, 4 H, HAr), 7.79 (d, J = 15.9 Hz, 1 H, =CH),
7.84 (d, 3J = 8.4 Hz, 1 H, HAr), 11.91 (s, 1 H, NH) ppm. 13C NMR
(75 MHz, [D6]DMSO): δ = 21.3, 27.7, 55.6, 55.7, 107.8, 111.8,
111.9, 112.6, 120.2, 121.7, 122.3, 122.9, 123.5, 123.8, 132.2, 137.2,
137.4, 143.8, 148.6, 149.6, 197.2 ppm. IR (KBr): ν = 3208, 1605,
˜
(3E)-4-[2-(2-Ethoxy-1-naphthyl)-6-methoxy-1H-indol-3-yl]but-3-en-
2-one (3n): Yellow solid. Yield: 0.91 g, 79 %. M.p. 116–117 °C
1569, 1486, 1464, 1456, 1259, 1247, 1236, 1224, 1144, 1030,
816 cm–1. MS (EI, 70 eV): m/z (%) = 335 (74) [M]+, 320 (28), 292
(73), 277 (20), 262 (49), 261 (100), 246 (24), 218 (57), 217 (31), 204
(45), 191 (21), 101 (23), 83 (33), 43 (68). C21H21NO3 (335.41): calcd.
C 75.20, H 6.31, N 4.18; found C 75.42, H 6.27, N 4.02.
1
3
(EtOH/acetone). H NMR (300 MHz, [D6]DMSO): δ = 1.16 (t, J
= 6.9 Hz, 3 H, CH3), 2.08 (s, 3 H, CH3), 3.83 (s, 3 H, OCH3), 4.19
(q, 3J = 6.9 Hz, 2 H, CH2), 6.67 (d, 3J = 15.9 Hz, 1 H, =CH), 6.88
(dd, 3J = 8.6, 4J = 2.1 Hz, 1 H, HAr), 6.92 (d, 4J = 2.1 Hz, 1 H,
3
H
Ar), 7.19 (d, J = 15.9 Hz, 1 H, =CH), 7.23–7.28 (m, 1 H, HAr),
(3E)-4-[2-(4-Bromophenyl)-6-methyl-1H-indol-3-yl]but-3-en-2-one
(3j): Yellow solid. Yield: 0.79 g, 74 %. M.p. 266–267 °C (EtOH/
acetone). 1H NMR (300 MHz, [D6]DMSO): δ = 2.26 (s, 3 H, CH3),
3
7.38–7.45 (m, 2 H, HAr), 7.63 (d, J = 9.0 Hz, 1 H, HAr), 7.92 (d,
3J = 8.6 Hz, 1 H, HAr), 7.95–8.01 (m, 1 H, HAr), 8.15 (d, 3J =
9.0 Hz, 1 H, HAr), 11.89 (s, 1 H, NH) ppm. 13C NMR (75 MHz,
[D6]DMSO): δ = 14.8, 27.9, 55.3, 64.5, 95.1, 110.6, 110.7, 115.1,
119.6, 120.4, 121.0, 123.9, 124.2, 127.4, 128.2, 128.3, 128.4, 131.4,
3
3
2.44 (s, 3 H, CH3), 6.85 (d, J = 16.0 Hz, 1 H, =CH), 7.06 (dd, J
= 8.1, 4J = 1.5 Hz, 1 H, HAr), 7.28 (d, 4J = 1.5 Hz, 1 H, HAr),
7.55 (d, J = 8.4 Hz, 2 H, HAr), 7.67 (d, J = 16.0 Hz, 1 H, =CH),
3
3
3
3
133.8, 136.7, 138.2, 138.6, 154.9, 156.2, 196.8 ppm. IR (KBr): ν =
˜
7.79 (d, J = 8.4 Hz, 2 H, HAr), 7.87 (d, J = 8.1 Hz, 1 H, HAr),
12.06 (s, 1 H, NH) ppm. 13C NMR (75 MHz, [D6]DMSO): δ =
21.3, 27.9, 108.6, 112.0, 120.4, 122.5, 122.6, 123.1, 123.6, 130.3,
131.3 (2 C), 131.9 (2 C), 132.7, 136.5, 137.4, 141.9, 197.2 ppm. IR
3234, 1603, 1575, 1456, 1262, 1160, 809 cm–1. MS (EI, 70 eV): m/z
(%) = 385 (1) [M]+, 150 (5), 129 (5), 121 (7), 115 (8), 75 (10), 43
(100). C25H23NO3 (385.47): calcd. C 77.90, H 6.01, N 3.63; found
C 78.17, H 6.05, N 3.46.
(KBr): ν = 3261, 1611, 1453, 1273, 1000, 829 cm–1. MS (EI, 70 eV):
˜
m/z (%) = 356/354 (1/1) [M]+, 231 (33), 115 (22), 102 (13), 75 (14),
43 (100). C19H16BrNO (354.25): calcd. C 64.42, H 4.55, N 3.95;
found C 64.48, H 4.42, N 3.96.
(3E)-4-[6-Chloro-2-(5-methyl-2-furyl)-1H-indol-3-yl]but-3-en-2-one
(3o): Brown solid. Yield: 0.72 g, 80 %. M.p. 267–268 °C (EtOH/
acetone). 1H NMR (300 MHz, [D6]DMSO): δ = 2.34 (s, 3 H, CH3),
3
3
2.43 (s, 3 H, CH3), 6.39 (d, J = 3.3 Hz, 1 H, HFur), 6.80 (d, J =
(3E)-4-[2-(4-Fluorophenyl)-6-methyl-1H-indol-3-yl]but-3-en-2-one
(3k): Yellow solid. Yield: 0.53 g, 60%. M.p. Ͼ250 °C (dec.; EtOH/
acetone). 1H NMR (300 MHz, [D6]DMSO): δ = 2.25 (s, 3 H, CH3),
3
3
16.2 Hz, 1 H, =CH), 6.98 (d, J = 3.3 Hz, 1 H, HFur), 7.17 (dd, J
= 8.4, 4J = 2.1 Hz, 1 H, HInd), 7.43 (d, 4J = 2.1 Hz, 1 H, HInd),
7.93 (d, 3J = 8.7 Hz, 1 H, HInd), 8.17 (d, J = 16.2 Hz, 1 H, =CH),
3
3
3
2.43 (s, 3 H, CH3), 6.84 (d, J = 16.0 Hz, 1 H, =CH), 7.05 (dd, J
12.17 (s, 1 H, NH) ppm. 13C NMR (75 MHz, [D6]DMSO): δ =
4
= 8.1, J = 1.5 Hz, 1 H, HAr), 7.27 (m, 1 H, HAr), 7.42–7.49 (m, 2
H, HAr), 7.62–7.70 (m, 3 H, =CH + HAr), 7.87 (d, 3J = 8.1 Hz, 1 H,
13.5, 27.4, 107.4, 108.8, 111.4, 112.5, 121.5, 121.9, 123.5, 124.4,
HAr), 12.03 (s, 1 H, NH) ppm. 13C NMR (75 MHz, [D6]DMSO): δ
127.7, 133.3, 135.9, 137.7, 144.2, 154.1, 197.4 ppm. IR (KBr): ν =
˜
3250, 1634, 1600, 1569, 1265, 1234, 1169, 1006, 959 cm–1. MS (EI,
70 eV): m/z (%) = 301/299 (4/13) [M]+, 221 (35), 193 (13), 178 (13),
96 (15), 43 (100). C17H14ClNO2 (299.76): calcd. C 68.12, H 4.71,
N 4.67; found C 67.96, H 4.61, N 4.72.
2
= 21.3, 27.9, 108.4, 112.0, 116.0 (d, JCF = 21.7 Hz, 2 C), 120.4,
4
3
122.2, 123.1, 123.6, 127.6 (d, JCF = 3.1 Hz), 131.6 (d, JCF
=
8.5 Hz, 2 C), 132.5, 136.6, 137.2, 142.4, 162.5 (d, 1JCF = 247.0 Hz),
197.2 ppm. IR (KBr): ν = 3187, 1601, 1569, 1483, 1453, 1276, 1235,
˜
1162, 1001, 839 cm–1. MS (EI, 70 eV): m/z (%) = 293 (86) [M]+,
279 (26), 278 (56), 251 (78), 250 (100), 249 (37), 248 (34), 236 (25),
235 (76), 234 (36), 77 (24), 59 (48), 43 (61). C19H16FNO (293.34):
calcd. C 77.80, H 5.50, N 4.77; found C 77.76, H 5.32, N 4.89.
(3E)-4-{2-[5-(2,4,6-Trichlorophenyl)-2-furyl]-1H-indol-3-yl}but-3-en-
2-one (3p): Red solid. Yield: 0.97 g, 75%. M.p. 276–277 °C (EtOH/
dioxane). 1H NMR (300 MHz, [D6]DMSO): δ = 2.30 (s, 3 H, CH3),
3
3
6.86 (d, J = 16.2 Hz, 1 H, =CH), 7.04 (d, J = 3.6 Hz, 1 H, HFur),
7.18–7.23 (m, 1 H, HAr), 7.25–7.31 (m, 1 H, HAr), 7.27 (d, 3J =
3.6 Hz, 1 H, HFur), 7.47–7.49 (m, 1 H, HAr), 7.93 (s, 2 H, HAr),
(3E)-4-[6-Chloro-2-(3,4-dimethoxyphenyl)-1H-indol-3-yl]but-3-en-2-
one (3l): Yellow solid. Yield: 0.81 g, 76%. M.p. 237–238 °C (EtOH/
acetone). 1H NMR (300 MHz, [D6]DMSO): δ = 2.27 (s, 3 H, CH3),
3
7.96–7.98 (m, 1 H, HAr), 8.27 (d, J = 15.6 Hz, 1 H, =CH), 12.21
(s, 1 H, NH) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 27.3,
108.8, 111.7, 112.2, 115.3, 120.9, 121.6, 123.8, 123.9, 125.5, 127.3,
128.7 (2 C), 131.3, 135.5, 135.9 (2C), 136.3, 137.3, 146.9, 147.1,
3
3.86 (s, 6 H, OCH3), 6.84 (d, J = 16.2 Hz, 1 H, =CH), 7.13–7.23
(m, 4 H, HAr), 7.47 (d, 4J = 1.8 Hz, 1 H, HAr), 7.77 (d, 3J = 16.2 Hz,
1 H, =CH), 7.98 (d, 3J = 8.4 Hz, 1 H, HAr), 12.18 (s, 1 H, NH)
ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 27.8, 55.7 (2 C), 107.8,
111.5, 111.9, 112.5, 121.4, 121.8, 122.4, 122.6, 122.9, 124.7, 127.3,
197.4 ppm. IR (KBr): ν = 3208, 1623, 1599, 1573, 1455, 1265, 1237,
˜
735 cm–1. MS (EI, 70 eV): m/z (%) = 435/433/431/429 (2/15/44/44)
[M]+, 322 (86), 288 (73), 209 (61), 207 (100), 178 (32), 101 (38), 59
(52). C22H14Cl3NO2 (430.72): calcd. C 61.35, H 3.28, N 3.25; found
C 61.34, H 3.26, N 3.38.
136.5, 137.2, 144.8, 148.9, 149.8, 197.2 ppm. IR (KBr): ν = 3228,
˜
1611, 1455, 1255, 1237, 1026, 1003 cm–1. MS (EI, 70 eV): m/z (%)
= 357/355 (1/3) [M]+, 277 (5), 191 (6), 113 (5), 96 (6), 43 (100).
C20H18ClNO3 (355.82): calcd. C 67.51, H 5.10, N 3.94; found C
67.57, H 5.01, N 3.95.
(3E)-4-{2-[5-(4-Methyl-2-nitrophenyl)-2-furyl]-1H-indol-3-yl}but-3-
en-2-one (3q): Red solid. Yield: 0.75 g, 65%. M.p. 272–273 °C
1
(3E)-4-[6-Chloro-2-(4-nitrophenyl)-1H-indol-3-yl]but-3-en-2-one (EtOH/dioxane). H NMR (300 MHz, [D6]DMSO): δ = 2.34 (s, 3
(3m): Red solid. Yield: 0.75 g, 74%. M.p. Ͼ250 °C (dec.; EtOH/
H, CH3), 2.45 (s, 3 H, CH3), 6.85 (d, 3J = 16.2 Hz, 1 H, =CH),
acetone). 1H NMR (300 MHz, [D6]DMSO): δ = 2.30 (s, 3 H, CH3), 7.00 (d, J = 3.9 Hz, 1 H, HFur), 7.18–7.24 (m, 1 H, HAr), 7.22 (d,
3
924
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 920–926

Furan Ring-Opening/Indole Ring-Closure
3J = 3.9 Hz, 1 H, HFur), 7.26–7.32 (m, 1 H, HAr), 7.47–7.50 (m, 1 by column chromatography (eluent: CH2Cl2/hexane, 1:3). The title
3
4
H, HAr), 7.47–7.50 (m, 1 H, HAr), 7.65 (dd, J = 8.1, J = 1.8 Hz,
product was obtained as a yellow solid (0.62 g, 56%). M.p. 99–
4
3
1
1 H, HAr), 7.84 (d, J = 1.8 Hz, 1 H, HAr), 7.94 (d, J = 8.1 Hz, 1 100 °C. H NMR (300 MHz, CDCl3): δ = 2.35 (s, 3 H, CH3), 4.52
H, HAr), 7.96–7.97 (m, 1 H, HAr), 8.20 (d, 3J = 16.2 Hz, 1 H, =CH),
(d, 3J = 3.9 Hz, 2 H, CH2), 5.71 (br. t, 3J = 3.9 Hz, 1 H, NH), 6.09
12.20 (s, 1 H, NH) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = (d, J = 3.3 Hz, 1 H, HFur), 6.45 (m, 2 H, HAr + HFur), 6.71 (dd,
3
4
3
20.4, 27.1, 108.9, 111.8, 112.2, 112.8, 119.7, 120.9, 121.6, 123.9,
124.2, 124.4, 125.5, 128.9, 131.2, 133.4, 136.3, 137.4, 140.3, 146.8,
3J = 8.1, J = 2.1 Hz, 1 H, HAr), 7.34 (d, J = 8.1 Hz, 1 H, HAr),
7.53 (d, 3J = 8.7 Hz, 2 H, HAr), 8.21 (d, 3J = 8.7 Hz, 2 H, HAr
)
147.2, 149.0, 197.6 ppm. IR (KBr): ν = 3287, 1626, 1602, 1573,
ppm. 13C NMR (75 MHz, CDCl3): δ = 13.7, 47.2, 107.5, 108.1,
111.2, 115.1, 117.6, 123.9 (2 C), 127.5 (2 C), 128.6, 134.3, 144.5,
146.5, 147.2, 150.5, 151.6 ppm. MS (EI, 70 eV): m/z (%) = 344/342
(33/100) [M]+, 274/272 (19/57), 220 (56), 143 (90), 115 (63), 89 (83),
45 (46). C18H15ClN2O3 (342.78): calcd. C 63.07, H 4.41, N 8.17;
found C 63.28, H 4.28, N 8.14.
˜
1518, 1434, 1271, 1236 cm–1. MS (EI, 70 eV): m/z (%) = 386 (100)
[M]+, 357 (22), 356 (55), 327 (20), 268 (24), 254 (23), 225 (23), 210
(26), 184 (61), 182 (23), 167 (20), 166 (25), 154 (25), 101 (24), 43
(42). C23H18N2O4 (386.41): calcd. C 71.49, H 4.70, N 7.25; found
C 71.67, H 4.60, N 7.22.
(3E)-4-[6-Chloro-2-(2-thienyl)-1H-indol-3-yl]but-3-en-2-one
(3r): Supporting Information (see footnote on the first page of this arti-
Yellow solid. Yield: 0.68 g, 75%. M.p. 237–238 °C (EtOH/acetone).
cle): General experimental procedures for the synthesis of the in-
1H NMR (300 MHz, [D6]DMSO): δ = 2.32 (s, 3 H, CH3), 6.87 (d, doles and 1H and 13C NMR spectra of the synthesized compounds.
3J = 15.9 Hz, 1 H, =CH), 7.21 (dd, 3J = 8.7, 4J = 2.1 Hz, 1 H,
H
Ind), 7.33 (dd, 3J = 5.1, 3J = 3.6 Hz, 1 H, HTh), 7.47 (d, 4J =
3
2.1 Hz, 1 H, HInd), 7.56 (dd, 4J = 1.2, J = 3.6 Hz, 1 H, HTh), 7.87
Acknowledgments
4
3
3
(dd, J = 1.2, J = 5.1 Hz, 1 H, HTh), 7.96 (d, J = 15.9 Hz, 1 H,
3
We thank the Russian Foundation of Basic Research (grant nos. 07-
03-00352-a and 10-03-00254-a), the Federal Agency for Education
(Rosobrazovanie) (grant no. 2.1.1/4628), and the Bayer HealthCare
AG (Germany) for the financial support of this work. Dr. V. E.
Zavodnik is acknowledged for X-ray crystal-structure determi-
nation.
=CH), 7.98 (d, J = 8.7 Hz, 1 H, HInd), 12.29 (s, 1 H, NH) ppm.
13C NMR (75 MHz, [D6]DMSO): δ = 27.9, 108.7, 111.6, 121.6,
121.9, 123.7, 124.5, 127.9, 128.5, 128.7, 129.4, 131.4, 135.3, 137.3,
137.5, 197.3 ppm. IR (KBr): ν = 3258, 1628, 1602, 1263, 1238,
˜
706 cm–1. MS (EI, 70 eV): m/z (%) = 303/301 (2/7) [M]+, 223 (55),
112 (40), 87 (14), 75 (15), 63 (21), 43 (100). C16H12ClNOS (301.80):
calcd. C 63.68, H 4.01, N 4.64; found C 63.65, H 3.98, N 4.64.
[1] a) Alkaloids 2001, thematic volume 56; b) R. J. Sundberg, S. Q.
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(1E)-1-[2-(5-Nitro-2-thienyl)-1H-indol-3-yl]pent-1-en-3-one (3s): Vi-
olet solid. Yield: 0.42 g, 43%. M.p. 227–228 °C (EtOH/acetone).
1H NMR (300 MHz, [D6]DMSO): δ = 1.06 (t, 3J = 7.4 Hz, 3 H,
3
3
CH3), 2.74 (q, J = 7.4 Hz, 2 H, CH2), 7.05 (d, J = 15.9 Hz, 1 H,
=CH), 7.23–7.28 (m, 1 H, HInd), 7.33–7.38 (m, 1 H, HAr), 7.51–
3
3
7.53 (m, 1 H, HInd), 7.60 (d, J = 4.5 Hz, 1 H, HTh), 7.96 (d, J =
15.9 Hz, 1 H, =CH), 8.03–8.05 (m, 1 H, HInd), 8.30 (d, 3J = 4.5 Hz,
1 H, HTh), 12.47 (s, 1 H, NH) ppm. 13C NMR (75 MHz, [D6]-
DMSO): δ = 8.2, 33.9, 111.8, 112.4, 121.1, 121.9, 124.7, 124.8,
125.5, 127.2, 130.7, 132.6, 132.9, 137.4, 139.6, 150.9, 199.9 ppm.
IR (KBr): ν = 3240, 1627, 1612, 1452, 1423, 1334, 1193, 813, 745,
˜
730 cm–1. MS (EI, 70 eV): m/z (%) = 326 (60) [M]+, 297 (100), 294
(69), 251 (65), 239 (50), 235 (61), 222 (47), 208 (34), 178 (28), 59
(24). C17H14N2O3S (326.38): calcd. C 62.56, H 4.32, N 8.58; found
C 62.36, H 4.19, N 8.50.
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Taliani, C. La Motta, A. M. Marini, S. Salerno, M. Bellandi,
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5798–5806.
5-Chloro-2-(5-methyl-2-furyl)-N-(4-nitrobenzylidene)aniline
(4m):
Aniline 1c (500 mg, 2.4 mmol) and p-nitrobenzaldehyde (2d;
364 mg, 2.4 mmol) were dissolved in acetic acid (5 mL) and stirred
at room temperature for 2 h. The mixture was cooled to 5–7 °C,
and the residue was removed by filtration and recrystallized from
glacial acetic acid. The product 4m was isolated as a red solid
(0.59 g, 72%). M.p. 164–165 °C. IR (KBr): ν = 3440, 1634, 1601,
˜
1519, 1103, 1021, 908, 859, 769, 735, 686 cm–1. MS (EI, 70 eV): m/z
(%) = 342/340 (33/100) [M]+, 299/297 (17/51), 283/281 (14/42), 215
(16), 44 (19). C18H13ClN2O3 (340.77): calcd. C 63.44, H 3.85, N
8.22; found C 63.36, H 3.76, N 8.07. Owing to the instability of
4m in solution we failed to record its NMR spectra. To prove the
structure of 4m, it was reduced with NaBH4 and characterized as
the corresponding amine.
5-Chloro-2-(5-methyl-2-furyl)-N-(4-nitrobenzyl)aniline:
NaBH4
(0.25 g, 6.4 mmol) was added portionwise to a solution of 4m
(1.1 g, 3.2 mmol) in a mixture of ethanol (20 mL) and 1,4-dioxane
(10 mL) at room temperature. The resulting mixture was heated at
reflux for 10 min, poured into H2O (200 mL) and neutralized with
NH4Cl. The residue formed was removed by filtration and purified
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into indoles 3 are given in the Supporting Information.
Received: October 31, 2009
Published Online: January 4, 2010
926
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 920–926