Metal halide hydrates as lewis acid catalysts for the conjugated Friedel-Crafts reactions of indoles and activated olefins

Article abstract of DOI:10.1590/S0103-50532011000400003

Metal halide hydrates such as SnCl₂·2H₂O, MnCl₂·4H₂O, SrCl₂·6H ₂O, CrCl₂·6H₂O, CoCl₂· 6H₂O e CeCl₃·7H₂O were investigated as mild Lewis acids catalysts for the conjugate Friedel-Crafts reaction between indoles and activated olefins. The reactions were carried out with aliphatic unsaturated ketones over a period of days at room temperature, while chalcones reacted only under reflux conditions. The reactions with nitrostyrenes were either performed in solvent or under solventless conditions. In all cases reasonable to good yields were obtained. ?2011 Sociedade Brasileira de Qui?mica.

Full text of DOI:10.1590/S0103-50532011000400003

J. Braz. Chem. Soc., Vol. 22, No. 4, 623-636, 2011.
Printed in Brazil - ©2011 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Article
A
Metal Halide Hydrates as Lewis Acid Catalysts for the Conjugated Friedel-Crafts
Reactions of Indoles and Activated Olefins
Cristiane S. Schwalm, Marco Antonio Ceschi and Dennis Russowsky*
Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500,
91501-970 Porto Alegre-RS, Brazil
O uso de haletos metálicos hidratados, tais como, SnCl2·2H2O, MnCl2·4H2O, SrCl2·6H2O,
CrCl2·6H2O, CoCl2·6H2O e CeCl3·7H2O como catalisadores ácidos de Lewis foi investigado nas
reações conjugadas tipo Friedel-Crafts entre indóis e olefinas ativadas. A utilização de enonas
alifáticas forneceu as respectivas b-indolilcetonas à temperatura ambiente em longos tempos de
reação, enquanto que nas reações com chalconas foi necessário o uso de condições de refluxo
em isopropanol. As reações dos indóis com nitroestirenos foram efetuadas tanto em fase líquida
como em condições sem solvente. Em todos os casos estudados foram obtidos rendimentos de
razoáveis a bons.
Metal halide hydrates such as SnCl2·2H2O, MnCl2·4H2O, SrCl2·6H2O, CrCl2·6H2O, CoCl2·6H2O
e CeCl3·7H2O were investigated as mild Lewis acids catalysts for the conjugate Friedel-Crafts
reaction between indoles and activated olefins. The reactions were carried out with aliphatic
unsaturated ketones over a period of days at room temperature, while chalcones reacted only
under reflux conditions. The reactions with nitrostyrenes were either performed in solvent or under
solventless conditions. In all cases reasonable to good yields were obtained.
Keywords: Friedel-Crafts, indoles, activated olefins, metal halide hydrates, Lewis acids,
Michael addition
Introduction
low yields, complex handling procedures and problematic
side reactions, such as dimerization and polymerization.12
On the other hand, the employment of suitable metal
halides such as InCl3,13 InBr3,14 SmI3,15 GaI3,16 SbCl3,17
The investigation of synthetic methodologies for the
preparation of 3-substituted indole derivatives has been
a continuous challenge in the chemistry of heterocyclic
compounds.1-3
The C3 alkylation reaction of indoles through the
conjugated Friedel-Crafts (CFC) reaction has received much
attention in the last decade.4-6 Not only they allow access
to advanced building blocks in the synthesis of natural
compounds, but also their diverse biological properties of
derivatives have pharmaceutical applications.7-11
Over the past few years a range of methods for the
preparation of b-indolylketones by CFC reaction of indoles
with a,b-unsaturated ketones has appeared in the literature
in which both Brønsted or Lewis acidic catalysts have
successfully been employed. However, in the curse of
Brønsted acid catalysis, many procedures involve strong
acidic conditions, expensive reagents, longer reaction times,
18
ScCl3,18 AlCl3,19 ZrCl4,20 and HfCl4 as Lewis acid
catalysts have attracted attention due to their ability to
efficiently activate the a,b-unsaturated carbonyl system
for the CFC reaction. However, many of them are
moisture sensitive needing a careful handling and the
achievement of a substitute is welcome.Additionally, others
environmentally-benign, oxygen and/or moisture tolerant
Lewis acids such as Yb(OTf)3,7 Sc(OTf)3,21 Bi(OTf)3,22
23
Hf(OTf)4,21 and Zr(OTf)4 have been applied to this
transformation, but they are expensive.
A few previous uses of metal salt hydrates such as:
NaAuCl4·2H2O,24 ZrOCl2·8H2O,25 RuCl3·nH2O26 and
Fe(BF4)2·6H2O27 have been reported.
As a part of our ongoing investigation searching for
moisture compatible Lewis acids, including their use
in protic solvents, for the synthesis of small molecules
of biological interest,28-36 we decide to investigate the
*e-mail: dennis@iq.ufrgs.br

624
Metal Halide Hydrates as Lewis Acid Catalysts for the Conjugated Friedel-Crafts Reactions of Indoles
J. Braz. Chem. Soc.
metal halide hydrates as a potential catalysts for the CFC
reaction. We have earlier demonstrated the successful use of
SnCl2·2H2O as an alcoholic compatible Lewis acid catalyst
for the multicomponent dihydropyrimidinone synthesis.37
The Lewis acidity of SnCl2·2H2O has been reported by
others in different reactions types.38-40
Although the hydrogen Brønsted acid catalysis has been
suggestedbySpencerasthemainprocesswhenametalhalide
is used as a Lewis catalyst in aqueous (or protic alcoholic)
solvents,41 other authors postulated the water-tolerance of
many metal halides. Kobayashi suggests that the certain
metal halides are able to complex with the electrophile before
the hydrolysis occurs. These characteristics depends on the
hydrolysis constant (Kh) within a certain range and a high
water-exchange rate constant (WERC).42 On the other hand,
Fringuelli et al.43 report the use ofAlCl3, TiCl4, and SnCl4 as
the Lewis acids catalysts in aqueous solvent. Although the
authors agree with the fast hydrolysis of metal salts, they
affirm that the hydrated metal cation remains as the effective
species as Lewis acid catalyst.
different alcoholic solvents, temperatures and catalyst
loading. In all experiments the desired b-indolylketone 3a
was obtained in good yield (Scheme 1).
As shown in Table 1, the yield of the product 3a was
quite good when the reaction was carried out in i-PrOH
at room temperature. The reaction proceeded cleanly46 as
observed by comparative TLC and i-PrOH was chosen as
the default solvent for the other reactions (c.f. entries 1-3).
Table 1. Synthesis of b-indolylketone 3a under different conditions
Lewis Acid
(equiv.)
time
(h)
Yield
(%)
entry
Solvent Temperature
•
1
SnCl2 2H2O (0.1) MeOH
r. t.
r. t.
96
96
96
96
96
120
120
120
3
82
88
96
97
90
93
70
79
98
98
98
•
2
SnCl2 2H2O (0.1)
EtOH
•
3
SnCl2 2H2O (0.1) i-PrOH
r. t.
•
4
SnCl2 2H2O (0.2) i-PrOH
r. t.
•
5
SnCl2 2H2O (0.5) i-PrOH
r. t.
•
6
MnCl2 4H2O (0.1) i-PrOH
r. t.
•
7
SrCl2 6H2O (0.1) i-PrOH
r. t.
Recent studies of Lindstrom44 show that the water tightly
coordinated to the metal halide become more labile upon
complexation of an organic ligand (electrophile), leading
to a higher rate of exchange with substrate molecules and
consequently to higher reaction rates.
•
8
CoCl2 6H2O (0.1) i-PrOH
r. t.
•
9
SnCl2 2H2O (0.1) i-PrOH
reflux
reflux
reflux
•
10
11
CoCl2 6H2O (0.1) i-PrOH
5
•
CrCl3 6H2O (0.1) i-PrOH
5
The SnCl2·2H2O was employed as a Lewis acid catalyst
in the esterification of oleic acid. The authors proved
the ethanol-compatibility of the catalyst as a Lewis acid
through the recovery of SnCl2·2H2O and verified that the
catalytic activity of the recovered SnCl2·2H2O remains
unaltered in successive reactions with oleic acid.45
Based on these previous studies, we report in this paper,
our efforts to apply a series of metal halide hydrates such as:
SnCl2·2H2O, MnCl2·4H2O, SrCl2·6H2O, CoCl2·6H2O and
CrCl3·6H2O as Lewis acid catalysts for the CFC reaction
of indoles and activated olefins, carried out in benign
alcoholic solvents.
For the SnCl2·2H2O, the increase of the catalyst loading
did not improve the yields and the catalytic amount of
10 mol% was chosen as the default load of the catalyst
(entries 3, 4 and 5, respectively).
Although long reaction times were required, in
general, reasonable to good yields were observed when
MnCl2·4H2O, SrCl2·6H2O, CoCl2·6H2O were used as
catalysts in experiments carried out at room temperature
(entries 6, 7 and 8). On the other hand, shorter reaction
times of 3-5 h and refluxing conditions were enough
to complete the consumption of the reagents when
SnCl2·2H2O, CoCl2·6H2O and CrCl2·6H2O were used
(entries 9, 10 and 11, respectively).
Results and Discussion
Due to the easy availability, good stability and low cost,
SnCl2·2H2O was chosen as the default catalyst. Its use as
a Lewis acid catalyst in the reaction of indoles 1a-c and
ketones 2a-e afforded the respective b-indolylketones 3b-m
in reasonable to good yields (Scheme 2). The results are
summarized in the Table 2.
Reactions of indoles with alkylidene-alkylketones
In our first experiment, we investigated the use of
various metal halide hydrates as Lewis acid catalysts in
the reaction of indole (1a) and 4-hexen-3-one (2a) under
As can be observed, the yields of adducts 3 were high,
except for the cases where cyclohexenone was used as the
Michael acceptor in the reactions with indole 1a (entries 4
and 9, respectively). In both cases, we were able to isolate
variable amounts of two other side products, which showed
a strong absorption in UV-light (254 nm).
Me
O
Metal Halide
Hydrate
+
Me
Me
N
N
O
Alcoholic
Solvent
H
H
Me
1a
2a
3a
Scheme 1. Synthesis of b-indolylketone 3a.

Vol. 22, No. 4, 2011
Schwalm et al.
625
•
Table 2. Synthesis b-Indolylketones 3b-m under SnCl2 2H2O catalyst at room temperature
R3
R2
O
R1
R1
O
R4
SnCl2 2H2O
+
R3
R4
N
H
R2
N
i-PrOH, r. t.
2a-e
H
3b-m
1a-c
Indole
R1
a,b-Unsaturated ketone
entry
time (h)
Product
Yield (%)
R2
H
R3
R4
Et
1
1a
1a
1a
1a
1b
1b
1b
1b
1b
1c
1c
1c
H
2a
H
C5H11
48
96
78
72
96
96
96
72
32
72
48
48
3b
3c
3d
3e
3f
96
96
96
40
98
80
90
95
41
88
97
81
2
H
H
2b
2c
2d
2e
2a
2b
2c
2d
2e
2a
2c
Me
3
H
H
cyclopentenone
cyclohexenone
Me
4
H
H
5
MeO
MeO
MeO
MeO
MeO
H
H
Et
Et
6
H
H
3g
3h
3i
7
H
C5H11
Me
8
H
cyclopentenone
cyclohexenone
Me
9
H
3j
10
11
12
Me
Me
Me
Et
Et
3k
3l
H
H
H
cyclopentenone
3m
We believe that the side products are generated
by a second attack of an indole molecule to the initial
b-indolylketone formed. Alternatively, a third molecule
of indole could be added to the bis-indolyl adduct 3n and
3o to form the tris-indolyl adduct 3p and 3q, respectively,
as reported recently by Shi et al.23 (Figure 1).
All of the yields refer to isolated products after
purification by column chromatography and the 1H NMR,
13C NMR and IR spectral data were in accordance with the
proposed structures.
Table 3). On the other hand, the use of reflux conditions
led to the formation of the desired adduct 3r after 5 h in
good yield (entry 4). Other catalysts such as MnCl2·4H2O,
SrCl2·6H2O, CoCl2·6H2O and CeCl3·7H2O were also
effective (entries 5 and 8).
The chalcones 2f-i were reacted under the previous
reaction conditions and the b-indolylchalcones 3r-z were
obtained in reasonable to good yields after purification
by column chromatography (entries 9-15). The lower
reactivity of chalcones may be attributed to their inferior
electrophilicity as well as the increase of steric hindrance
at the b-position of the ketone.
Reactions of indoles with arylidene-phenylketones
Next, we investigated the conjugated Friedel-Crafts
reaction of indoles 1a-c with chalcones47 2f-i in presence
of SnCl2·2H2O as the catalyst and i-PrOH as the solvent
(Scheme 2).
In contrast with alkylidene-alkylketones, the chalcone
2f was not reactive with indole 1a at room temperature over
144 h, even at 50 mol% catalyst loading (cf. entries 1-3,
Reactions of indoles with nitrostyrenes
Due to the success of previous experiments we
decided to investigate the CFC reactions of indoles 1a-c
with nitroolefins 4a-g. The nitroolefins are recognized
as excellent Michael aceptors48,49 and their derivatives
are important intermediates in organic synthesis
H
N
H
N
N H
O
OH
Indolyl Ketones
3e R = H
3j R = OMe
Bis-Indolyl adducts
Tris-Indolyl adducts
N
N
H
N
H
3n R = H
3p R = H
H
3o R = OMe
3q R = OMe
Figure 1. The possible structures of bis- and tris-indolyl adducts.

626
Metal Halide Hydrates as Lewis Acid Catalysts for the Conjugated Friedel-Crafts Reactions of Indoles
J. Braz. Chem. Soc.
Ar
O
R1
O
R1
Catalyst
10 mol%
+
Ar
N
R2
i-PrOH
N
R2
H
2f-i
1a-c
3n-v
H
Scheme 2. Conjugated Friedel-Crafts reaction of indoles 1a-c with chalcones 2f-i.
Table 3. Synthesis of b-indolylketones 3r-z via Scheme 2
Indole
Olefin
entry
Catalyst (equiv.)
Temperature
time (h)
3 / Yield (%)
R1
H
R2
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Ar
•
1
Ph
SnCl2 2H2O (0.1)
r. t.
144
144
144
5
3r / -
3r / -
•
2
H
Ph
Ph
SnCl2 2H2O (0.2)
r. t.
•
3
H
SnCl2 2H2O (0.5)
r. t.
3r / -
•
4
H
Ph
SnCl2 2H2O (0.1)
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
3r / 96
3r / 60
3r / 60
3r / 85
3r / 98
3s / 60
3t / 80
3u / 74
3v / 96
3w / 70
3x / 95
3y / 92
3z / 87
•
5
H
Ph
MnCl2 4H2O (0.1)
8
•
6
H
Ph
SrCl2 6H2O (0.1)
5
•
7
H
Ph
CoCl2 6H2O (0.1)
5
•
8
H
Ph
CeCl3 7H2O (0.1)
5
•
9
H
1-naftyl
4-MeO-C6H4
2-thienyl
Ph
SnCl2 2H2O (0.1)
5
•
10
11
12
13
14
15
16
H
SnCl2 2H2O (0.1)
5
•
H
SnCl2 2H2O (0.1)
5
•
MeO
MeO
MeO
MeO
H
SnCl2 2H2O (0.1)
5
•
1-naftyl
4-MeO-C6H4
2-thienyl
Ph
SnCl2 2H2O (0.1)
5
•
SnCl2 2H2O (0.1)
5
•
SnCl2 2H2O (0.1)
5
•
SnCl2 2H2O (0.1)
5
due to the synthetic versatility of the nitro-group as
precursor of other organic functionalities.50-52 First, we
investigated the reaction of indole 1a wiyh nitrostyrene
4a carried out under the reactions conditions described
above (i-PrOH, room temperature and 10 mol% of
SnCl2·2H2O). Unfortunately, no product was formed
even after 6 days. A second experiment was carried out
under reflux conditions over 5 h and total consumption
of the starting materials was observed. The TLC
analysis revealed the presence of very polar mixture of
byproducts53 which were not identified. After purification
by chromatography, product 5a was obtained in only
54% yield (Scheme 3).
The reaction was carried out in i-PrOH under reflux
conditions for 2 h, when total consumption of the starting
material was observed by TLC. After purification by
chromatography, the nitro-adduct 5a was isolated in 95%
yield (Table 4, entry 1).
At this point we decided to investigate a set of different
solvents. The experiments were carried out in polar protic
•
Table 4. Synthesis of adduct 5a promoted by CoCl2 6H2O under different
solvents
Ph
NO2
CoCl2 6H2O
+
NO2
Solvent
Reflux
N
N
5a
H
4a
H
1a
With the aim of improving the chemo-selectivity of
the reaction and the yields of the products, the catalyst
was changed to CoCl2·6H2O, which had been successfully
applied previously (see Table 1 entry 10 and Table 3,
entry 7, respectively).
time
(h)
Yield
(%)
entry
Catalyst
Solvent
Temperature
•
1
2
3
4
5
6
7
CoCl2 6H2O
i-PrOH
MeOH
EtOH
THF
2
reflux
reflux
reflux
reflux
reflux
reflux
reflux
95
72
73
58
55
0
•
CoCl2 6H2O
2
•
CoCl2 6H2O
2
Ph
•
CoCl2 6H2O
2
SnCl2 2H2O
10 mol%
NO2
•
CoCl2 6H2O
CH3CN
CH2Cl2
C6H6
2
+
NO2
Isopropanol
Reflux
N
N
•
5a
H
4a
CoCl2 6H2O
2
H
1a
•
CoCl2 6H2O
2
71
Scheme3. ConjugatedFriedel-Craftsreactionofindolewithnitrostyrene4a.

Vol. 22, No. 4, 2011
Schwalm et al.
627
Table 5. Synthesis of adduct 5a under different catalysts in solventless
conditions
solvents such as MeOH and EtOH; polar non protic
solvents such as THF, CH3CN and CH2Cl2 and in the non
polar non protic solvent such as C6H6. The results are
shown in Table 4.
As can be seen, the best result was achieved when the
reaction was carried out under reflux of i-PrOH (Table 4,
entry 1). On the other hand, the reaction did not proceed in
CH2Cl2 (entry 6). It should be noted that the yield of product
5a in the reaction performed in C6H6 was similar to those
obtained in MeOH or EtOH (entries 7, 2 and 3, respectively).
Ph
Catalyst
NO2
10 mol%
+
NO2
Solventless
100 oC
N
N
5a
H
4a
H
1a
Entry
Catalyst
Condition
time
(h)
Temp.
(°C)
Yield
(%)
•
1
2
3
4
5
6
7
CoCl2 6H2O solventless
0,25
0,50
0,50
2
100
100
100
100
100
100
100
97
81
93
95
95
96
57
•
CrCl3 6H2O solventless
•
CeCl3 7H2O solventless
•
MnCl2 4H2O solventless
Solventless CFC reactions of indoles with nitrostyrenes
•
NiCl2 6H2O solventless
8
•
SrCl2 6H2O solventless
12
Due to the constant search for environmentally-friendly
protocols that avoid the collateral production of wastes
in the synthetic organic chemistry, many efforts have
been made to develop organic reactions in solventless
conditions.54-56
Therefore, we decided to investigate the viability of
CFC reaction of indoles and nitrostyrenes catalyzed by
metal halide hydrates under solventless conditions. The
results are summarized in Table 5.
The best result was achieved when CoCl2·6H2O was
employed over 15 min at 100 °C (entry 1). Good yields
were also achieved with CrCl3·6H2O and CeCl3·7H2O with
little increase of the reaction times (entries 2 and 3). The
employment of MnCl2·4H2O, NiCl2·6H2O or SrCl2·6H2O
showed lower activity and an increase of the reaction time
was needed to complete the consumption of the reagents
(entries 4-6, respectively). In presence of SnCl2·2H2O, even
over prolonged time, poor yield was obtained (entry 7).
To explore the generality of the solventless conjugated
Friedel-Crafts reaction, we synthesized a set of nitrostyrene
derivatives through a methodology reported in the
literature.57 Reaction of nitromethane with various aromatic
aldehydes in the presence of ammonium acetate under
heating (Scheme 4) afforded the respective nitroolefins
4a-g in 65-89% yields, after recrystallization (Figure 2).
The solventless CFC reactions were carried out under
the same conditions disclosed above and afforded the
respective nitro adducts 5b-q. The results are summarized
in Table 6.
•
SnCl2 2H2O solventless
120
In general, all reactions afforded the nitro-adducts in
good yields. The reactivity of the nitroolefin 4d was lower
for both indoles 1a and 1b (entries 3 and 10, respectively).
This may be due to the strong electron releasing effect of the
N,N-dimethyl group attached at 4-position of the aromatic
ring.Also, the steric hindrance caused by the bulky naphtyl
group could be responsible for de increase of the reaction
times with the indoles 1a and 1c and the nitroolefin 4f
(entry 5 and 15, respectively).
O
AcONH4
NO2
CH3NO2
+
R
R
H
6a-g
4a-g
7
Scheme 4. Synthesis of nitroolefins 4a-g.
Synthesis of b-carboline derivative via Pictet-Spengler
reaction
To demonstrate the synthetic utility of the nitro adduct
intermediate 5a we performed the transformation of
the nitro group into an amino group by reduction in the
presence of NH4OAc and catalytic amounts of Pd/C.58
The triptamine derivative 8 was obtained in 90% yield as
a crude product.
After the treatment of compound 8 with benzaldehyde
under the Pictet-Spengler reaction conditions, the
NO2
NO2
NO2
NO2
Me
N
MeO
F
4d 89%
4c 65%
4b 84%
4a 86%
Me
NO2
MeO
NO2
NO2
S
MeO
4g 73%
4e 80%
4f 81%
Figure 2. Structures of nitroolefins 4a-g.

628
Metal Halide Hydrates as Lewis Acid Catalysts for the Conjugated Friedel-Crafts Reactions of Indoles
J. Braz. Chem. Soc.
Table 6. Synthesis of adduct 5b-q by CFC reaction under solventless conditions
Ar
R1
R1
NO2
CoCl2 6H2O
10 mol%
NO2
+
Ar
Solventless
100 °C
N
H
R2
N
H
R2
5b-q
4a-g
1a-c
entry
Indole
R1
Nitroolefin
time (min)
Product
Yield (%)
R2
Ar
1
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
1b
1c
1c
1c
H
H
H
4b
4c
4d
4e
4f
4-MeO-C6H4
4-F-C6H4
15
15
60
15
30
15
15
15
15
30
15
15
15
15
30
15
5b
5c
5d
5e
5f
92
97
98
90
97
98
95
86
96
87
98
98
93
94
93
98
2
H
3
H
H
4-N,N(Me)2-C6H4
3,4-(MeO)-C6H3
1-naphtyl
4
H
H
5
H
H
6
H
H
4g
4a
4b
4c
4d
4e
4f
2-thienyl
5g
5h
5i
7
MeO
MeO
MeO
MeO
MeO
MeO
MeO
H
H
Ph
8
H
4-MeO-C6H4
4-F-C6H4
9
H
5j
br.
10
11
12
13
14
15
16
H
4-N,N(Me)2-C6H4
3,4-(MeO)-C6H3
1-naphtyl
5k
5l
H
H
5m
5n
5o
5p
5q
H
4g
4a
4f
2-thienyl
Me
Me
Me
Ph
H
1-naphtyl
H
4g
2-thienyl
Ph
Ph
Ph
Ph
Pd/C
NH4OAc
PhCHO
+
N
N
H
NO2
TFA
r.t.; 72 h
NH2
MeOH
r.t.; Overnight
N
H
H
N
H
N
H
N
H
5a
8
9-trans
9-cis
Scheme 5. Synthesis of 1,2,3,4-tetrahydro-b-carbolines.
b-Carboline derivative 9 was isolated as a diastereomeric
mixture of 87:13 ratios. After purification by
chromatography, the compound 9-trans was isolated in
70% yield. The relative trans configuration of the major
distereoisomer was inferred by comparison of the 1H NMR
data with the reported literature (Scheme 5).59
SnCl2·2H2O, MnCl2·4H2O, CrCl2·6H2O, CoCl2·6H2O were
all effective.
Chalcones as Michael acceptors afforded the desired
adducts only under refluxing conditions using SnCl2·2H2O
as catalysts.
For the reaction with of nitroolefins, refluxing conditions
are imperative under the liquid phase. Here, the alcoholic
i-PrOH was superior. On the other hand, SnCl2·2H2O leads
to the formation of several byproducts and therefore it was
abandoned. The best results were achieved in the presence
of CoCl2·6H2O. These reactions were also investigated
in the absence of solvents under 100 °C. The metal
halide hydrates CoCl2·6H2O, CrCl3·6H2O, CeCl3·7H2O,
MnCl2·4H2O, NiCl2·6H2O and SrCl2·6H2O were all
effective in the reaction, but with different reaction times.
The CoCl2·6H2O, CrCl3·6H2O and CeCl3·7H2O were the
most effective catalysts. In summary, we have demonstrated
the use of cheaper and easy to handle metal halide hydrates
Conclusions
We have demonstrated that many metal halides hydrates
are able to catalyze the conjugate Friedel-Crafts reaction
of indoles and activated olefins in good to excellent yields.
The alcoholic solvents were superior and i-PrOH was found
to be the best choice.
For the reactions with aliphatic enones longer reaction
times were needed for those reaction carried out at
room temperature, whereas shorter times were observed
under refluxing conditions. The metal halide hydrates

Vol. 22, No. 4, 2011
Schwalm et al.
629
as Lewis acids catalysts in the conjugated Friedel-Crafts
reaction under enviromentally benign alcoholic solvents or
under eco-friendly solventless protocols.
1-(1H-Indol-3-yl)pentan-3-one (3b):61 96%, brown
solid, mp 86-87 °C; 1H NMR (300 MHz, CDCl3) d 8.20
(br s, 1H), 7.56 (d, J 7.8 Hz, 1H), 7.27 (d, J 8.1Hz, 1H),
7.20-7.05 (m, 2H), 6.89 (d, J 1.8 Hz, 1H), 3.03 (t, J 7.2
Hz, 2H), 2.77 (t, J 7.2 Hz, 2H), 2.26 (q, J 7.5 Hz, 2H),
1.01 (t, J 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 211.8,
136.2, 127.0, 121.8, 121.5, 119.0, 118.5, 114.9, 111.2,
42.7, 35.9, 19.3, 7.7; IR nmax/cm-1 (KBr) 3323 (NH), 1704
(C=O), 1458, 736.
Experimental
All reactions were carried out under air. The chalcones47
(2f-i) and the nitrostyrenes57 (4a-g) were prepared according
to the literature. All other reagents and solvents were
purchased from commercial suppliers and used without
further purification except hexane which was distilled prior
to use. The 1H and 13C NMR spectra were recorded in CDCl3
on aVarianVNMRS spectrometer at 300 MHz and 75 MHz,
respectively. The chemical shifts (d) are reported in ppm
relative to TMS (0.00 ppm) for 1H NMR and to the central
line of CDCl3 (77.0 ppm) for 13C NMR. Coupling constants
J are reported in Hertz (Hz). IR spectra were recorded on
a FTIR-Varian 640-IR spectrometer. Melting points were
measured on an Olympus BX41 microscope equipped
with a Mettler-Toledo FP82HT hot stage (Mettler-Toledo
FP90 controller) and are uncorrected. Reactions were
monitored using thin layer chromatography (TLC) carried
out on Merck silica gel 60 F254 precoated aluminium plates.
The visualization was achieved under UV light (254 nm)
or staining with I2. Chromatographic separations were
achieved on silica gel columns (70-230 mesh, Aldrich)
using gradient of hexanes/ethyl acetate as eluent.
4-(1H-Indol-3-yl)nonan-2-one (3c):60 96%, viscous
brown oil; 1H NMR (300 MHz, CDCl3) d 8.09 (br s, 1H),
7.64 (d, J 7.8 Hz, 1H), 7.31 (d, J 7.8 Hz, 1H), 7.21-7.05
(m, 2H), 6.91 (d, J 2.4 Hz, 1H), 3.43 (m, 1H), 2.88 (dd,
J 15.9 and 7.5 Hz, 1H), 2.78 (dd, J 15.9 and 6.9 Hz, 1H),
2.00 (s, 3H), 1.62-1.82 (m, 2H), 1.23 (br s, 6H), 0.81 (br
s, 3H); 13C NMR (75 MHz, CDCl3) d 209.2, 136.5, 126.5,
121.8, 121.2, 119.2, 119.1, 118.8, 111.3, 50.2, 35.8, 32.9,
31.8, 30.4, 27.2, 22.5, 14.0; IR nmax/cm-1 (neat, film) 3412
(NH), 2956, 2928, 2856, 1707 (C=O), 1458, 1357, 742 .
3-(1H-Indol-3-yl)-cyclopentanone ( 3 d ):61 96%,
viscous brown oil; 1H NMR (300 MHz, CDCl3) d 8.34 (br
s, 1H), 7.60 (d, J 7.8 Hz, 1H), 7.32 (dd, J 7.8 and 0.9 Hz,
1H), 7.19 (dt, J 7.5 and 1.2 Hz, 1H), 7.12 (dt, J 7.5 and
1.2 Hz, 1H), 6.88 (d, J 1.8 Hz, 1H), 3.65 (m, 1H), 2.72 (dd,
J 18.0 and 7.2 Hz, 1H), 2.65-2.17 (m, 4H), 2.17-1.98 (m,
1H); 13C NMR (75 MHz, CDCl3) d 220.0, 136.6, 126.5,
122.1, 120.0, 119.2, 118.9, 118.2, 111.3, 45.2, 38.1, 33.6,
29.7; IR nmax/cm-1 (neat, film) 3410 (NH), 1734 (C=O),
1458, 1401, 1230, 1169, 744.
General procedure for the synthesis of b-indolylketones
3a-m
In a 25 mL round-bottom flask, equipped with magnetic
stirrer were added the indoles 1a-c (1.0 mmol), the
a,b-unsaturated ketones 2a-e (1.1 mmol) and SnCl2·2H2O
(0.1mmol)ini-PrOH(2mL).Thereactionmixturewasstirred
at room temperature for the appropriate time shown in the
Table 2. After the completion of the reaction, monitored by
TLC, the solvent was removed under vacuum and the crude
products3a-mwerepurifiedbycolumnchromatographyusing
a gradient of hexanes/ethyl acetate as eluent.
3-(1H-Indol-3-yl)-cyclohexenone (3e):60 40%, viscous
brown oil; 1H NMR (300 MHz, CDCl3) d 8.18 (br s, 1H),
7.61 (d, J 7.8 Hz, 1H), 7.34 (d, J 8.1 Hz, 1H), 7.20 (t,
J 7.5 Hz, 1H), 7.11 (t, J 7.5 Hz, 1H), 6.94 (d, J 1.5 Hz,
1H), 3.43 (m, 1H), 2.92-2.72 (m, 1H), 2.72-2.57 (m, 1H),
2.57-2.33 (m, 2H), 2.33-2.16 (m, 1H), 2.16-1.62 (m, 3H);
13C NMR (75 MHz, CDCl3) d 212.1, 136.4, 126.0, 122.1,
120.4,119.5,119.2,118.9,111.3,48.0,41.5,35.9,31.6,24.8;
IR nmax/cm-1 (neat, film) 3411 (NH), 2971, 1705 (C=O),
1458, 1375, 1354, 1340, 743.
5-(1H-Indol-3-yl)hexan-3-one (3a):60 96%, viscous
brown oil; 1H NMR (300 MHz, CDCl3) d 8.25 (br s, 1H),
7.63 (m, 1H), 7.28 (m, 1H), 7.18-7.04 (m, 2H), 6.82 (s,
1H), 3.62 (m, 1H), 2.86 (dd, J 15.9 and 6.3 Hz, 1H), 2.64
(dd, J 15.9 and 8.1 Hz, 1H), 2.31 (q, J 7.2 Hz, 2H), 1.34 (d,
J 6,9 Hz, 3H), 0.96 (t, J 7.2 Hz, 3H); 13C NMR (75 MHz,
CDCl3) d 211.8, 136.4, 126.0, 121.7, 120.5, 120.2, 118.9,
118.9, 111.3, 50.1, 36.3, 26.9, 21.1, 7,6; IR nmax/cm-1 (neat,
film) 3411 (NH), 2971, 1705 (C=O), 1458, 1375, 1354,
1341, 743.
5-(5-Methoxy-1H-indol-3-yl)hexan-3-one (3f):62 98%,
viscous brown oil; 1H NMR (300 MHz, CDCl3) d 8.29 (br
s, 1H), 7.16 (d, J 8.7 Hz, 1H), 7.06 (d, J 2.1 Hz, 1H), 6.86
(d, J 2.1 Hz, 1H), 6.83 (dd, J 8.7 and 2.1 Hz, 1H), 3.84 (s,
3H), 3.59 (m, 1H), 2.86 (dd, J 15.9 and 6.0 Hz, 1H), 2.65
(dd, J 15.9 and 8.4 Hz, 1H), 2.32 (q, J 7.2 Hz, 2H), 1.34 (d,
J 6.9 Hz, 3H), 0,98 (t, J 7.2 Hz, 3H); 13C NMR (75 MHz,
CDCl3) d 211.6; 153.5, 131.6, 126.4; 121.0; 120.4, 112.0,

630
Metal Halide Hydrates as Lewis Acid Catalysts for the Conjugated Friedel-Crafts Reactions of Indoles
J. Braz. Chem. Soc.
111.7, 100.9, 55.8, 50.0, 36.3, 26.8, 21.1, 7.5; IR nmax/cm-1
(neat, film) 3407 (NH), 3383, 2964, 1705 (C=O).
1H), 7.59 (m, 1H), 7.17-7.10 (m, 1H), 7.09-6.98 (m, 2H),
3.55 (m, 1H), 2.97 (dd, J 15.6 and 7.8 Hz), 2.76 (dd, J 15.6
and 7.2 Hz), 2.32-2.21 (m, 5H), 1.39 (d, J 7.2 Hz, 3H), 0.87
(d, J 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 211.8, 135.4,
130.4, 126.8, 120.3, 118.7, 118.6, 114.6, 110.5, 49.1, 36.5,
27.1, 21.0, 11.6, 7.5; IR nmax/cm-1 (neat, film) 3400 (NH),
2969, 2933, 1705 (C=O), 1461, 742. HRMS (ESI+, m/Na+)
Found: 252.13575. Calc. for C15H19ON/Na+: 252.13589.
1-(5-Methoxy-1H-indol-3-yl)-pentan-3-one (3g):
1
80%, brown solid, mp 94-95 °C; H NMR (300 MHz,
CDCl3) d 7.89 (br s, 1H), 7.24 (d, J 8.7 Hz, 1H), 7.02 (d,
J 2.4 Hz, 1H), 6.96 (d, J 2.4 Hz, 1H), 6.85 (dd, J 8.7 and
2.4 Hz, 1H), 3.87 (s, 3H), 3.02 (t, J 7.5 Hz, 2H), 2.81 (t,
J 7.5 Hz, 2H), 2.42 (q, J 7.2 Hz, 2H), 1.05 (t, J 7.2 Hz,
3H); 13C NMR (75 MHz, CDCl3) d 211.5, 153.9, 131.4,
127.6, 122.2, 115.1, 112.2, 111.8, 100.6, 56.0, 42.6, 36.1,
19.4, 7.8; IR nmax/cm-1 (KBr) 3340 (NH), 1704 (C=O),
1487, 1456, 1211, 1173, 806. HRMS(ESI+, m/Na+) Found:
254.11510. Calc. for C14H17O2N/Na+: 254.11515.
1-(2-Methyl-1H-indol-3-yl)pentan-3-one (3l): 97%,
viscous brown oil;1H NMR (300 MHz, CDCl3) d 7.91 (br
s, 1H), 7.44 (m, 1H), 7.20-6.94 (m, 3H), 2.95 (t, J 7.2 Hz,
2H), 2.68 (t, J 7.2 Hz, 2H), 2.35-2.20 (m, 5H), 0.97 (t,
J 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 211.9, 135.1,
131.1, 128.0, 120.6, 118.8, 117.5, 110.3, 110.0, 42.7, 36.1,
18.4, 11.2, 7.6; IR nmax/cm-1 (neat, film) 3400 (NH), 2975,
2936, 2919, 1708 (C=O), 1462, 742. HRMS (ESI+, m/Na+)
Found: 238.12015. Calc. for C14H17ON/Na+: 238.12024.
4-(5-Methoxy-1H-indol-3-yl)-nonan-2-one (3h):60
90%, viscous brown oil; 1H NMR (300 MHz, CDCl3) d 8.35
(br s, 1H), 7.16 (d, J 8.7 Hz, 1H), 7.08 (d, J 2.4Hz, 1H), 6.87
(d, J 2.4Hz, 1H), 6.82 (dd, J 8.7 and 2.4 Hz, 1H), 3.85 (s,
3H), 3.42 (m, 1H), 2.85 (dd, J 15.9 and 7.5 Hz, 1H), 2.76
(dd, J 15.9 and 6.9 Hz, 1H), 2.00 (s, 3H), 1.60-1.80 (m, 2H),
1.38-1,07 (br s, 6H), 0.81 (br s, 3H); 13C NMR (75 MHz,
CDCl3) d 209.3, 153.4, 131.7, 126.8, 122.0, 118.3, 111.9,
111.5, 101.2, 55.8, 50.0, 35.7, 32.6, 31.7, 30.3, 27.1, 22.4,
13.9; IR nmax/cm-1 (neat, film) 3408 (NH), 2954, 2929, 1707
(C=O), 1484, 1457, 1215.
3-(2-Methyl-1H-indol-3-yl)-cyclopentanone (3m):46
81%, yellow solid; mp 135-136 °C; 1H NMR (300 MHz,
CDCl3) d 7.98 (br s, 1H), 7.53 (d, J 7.5 Hz, 1H), 7.28 (d,
J 7.8 Hz, 1H), 7.23-7.00 (m, 2H), 3.59 (m, 1H), 2.87-2.20
(m, 10H); 13C NMR (75 MHz, CDCl3) d 219.8, 135.5,
130.9, 126.7, 120.9, 119.1, 118.6, 111.8, 110.7, 44.3, 39.4,
34.5, 29.7, 12.1; IR nmax/cm-1 (KBr) 3342 (NH), 2961, 2897,
1729 (C=O), 1461, 1231, 1137, 743.
3-(5-Methoxy-1H-indol-3-yl)-cyclopentanone (3i):
1
viscous brown oil, 95%; H NMR (300 MHz, CDCl3) d
General procedure for the synthesis of b-indolylchalcones
3r-z
8.45 (br s, 1H), 7.21 (d, J 8.7 Hz, 1H), 7.05 (d, J 2.4 Hz,
1H), 6.88 (d, J 2.1 Hz, 1H), 6.87 (dd, J 8.7 and 2.1 Hz, 1H),
3.85 (s, 3H), 3.62 (m, 1H), 2.72 (dd, J 18.0 and 7.2 Hz, 1H),
2.55-2.22 (m, 4H), 2.15-1.98 (m, 1H); 13C NMR (75 MHz,
CDCl3) d 219.8, 153.5, 131.7, 126.8, 120.8, 117.7, 112.0,
111.9, 100.9, 55.8, 45.1, 37.9, 33.4, 29.5; IR nmax/cm-1
(neat, film) 3408 (NH), 1736 (C=O), 1485, 1457, 1440,
1212, 1167.
In a 25 mL round-bottom flask, equipped with a reflux
condenser and magnetic stirrer were added the indoles
1a-c (1.0 mmol), the chalcones 2f-i (1.1 mmol), and
SnCl2·2H2O (0.1 mmol) in i-PrOH (2 mL). The reaction
mixture was heated to reflux and stirred for the appropriate
time showed in the Table 3. After the completion of the
reaction, monitored byTLC, the solvent was removed under
vaccum and the crude products3r-z were purified by column
chromatography using hexanes/ethyl acetate as eluant.
3-(5-Methoxy-1H-indol-3-yl)-cyclohexanone (3j):58
41%, viscous brown oil,; H NMR (300 MHz, CDCl3)
1
d 8.11 (br s, 1H), 7.24 (d, J 8.7, 1H), 7.03 (d, J 2.4 Hz, 1H),
6.95 (d, J 2.1 Hz, 1H), 6.94 (dd, J 8.7 and 2.4 Hz, 1H),
3.84 (s, 3H), 3.39 (m, 1H), 2.86-2.73 (m, 1H), 2.63-2.51
(m, 1H), 2.51-2.33 (m, 2H), 2.33-2.20 (m, 1H), 2.13-1.73
(m, 3H); 13C NMR (75 MHz, CDCl3) d 212.0, 153.8, 131.6,
126.4, 121.2, 119.2, 112.2, 112.0, 110.9, 56.0, 48.0, 41.5,
35.8, 31.5, 24.9; IR nmax/cm-1 (neat, film) 3406 (NH), 2360,
1701 (C=O), 1484, 1456, 1216, 1171.
3-(1H-Indol-3-yl)-1,3-diphenylpropan-1-one (3r):64
96%,brownish solid, mp 130-131 °C; 1H NMR (300 MHz,
CDCl3) d 8.03 (br s, 1H), 7.91 (d, J 7.5 Hz, 2H), 7.51 (t,
J 7.2 Hz, 1H), 7.46-7.06 (m, 10H), 6.99 (t, J 7.2 Hz, 1H),
6.90 (s, 1H), 5.05 (m, 1H), 3.80 (dd, J 16.8 and 6.9 Hz,
1H), 3.70 (dd, J 16.8 and 7.8 Hz, 1H); 13C NMR (75 MHz,
CDCl3,) d 198.7, 144.2, 137.0, 136.6, 133.0, 128.5, 128.4,
128.1, 127.8, 126.5, 126.2, 122.0, 121.4, 119.4, 119.3,
119.1, 111.1, 45.2, 38.2; IR nmax/cm-1 (KBr) 3411 (NH),
1681 (C=O), 1456, 1448, 745, 700.
5-(2-Methyl-1H-indol-3-yl)-hexan-3-one (3k): 88%,
viscous brown oil; 1H NMR (300 MHz, CDCl3) d 7.96 (br. s,

Vol. 22, No. 4, 2011
Schwalm et al.
631
3-(1H-Indol-3-yl)-3-(naphthalen-1-yl)-1-phenyl-
propan -1-one (3s): 60%, brownish solid, mp 97-98 °C;
1H NMR (300 MHz, CDCl3) d 8.29 (m, 1H), 7.96-
7.80 (m, 4H), 7.68 (d, J 7.5 Hz, 1H), 7.54-7.17 (m,
9H), 7.09 (m, 1H), 6.96 (m, 1H), 6.70 (s, 1H), 5.92
(m, 1H), 3.94 (dd, J 17.4 and 7.8 Hz, 1H), 3.73 (dd,
J 17.4 and 6.3 Hz, 1H); 13C NMR (75 MHz, CDCl3,) d
198.5, 139.9, 137.0, 136.6, 134.0, 133.1, 131.4, 128.8,
128.6, 128.0, 127.0, 126.6, 126.1, 125.5, 125.3, 124.4,
123.6, 122.2, 122.0, 119.4, 119.3, 118.9, 111.2, 44.6,
33.2; IR nmax/cm-1 (KBr) 3412 (NH), 3055, 1681 (C=O),
1596, 1448, 1337, 1269, 780, 743; HRMS (ESI+, m/Na+)
Found: 398.15161.Calc. for C27H21ON/Na+: 398.15154.
7.94 (d, J 7.8 Hz, 2H), 7.90-7.78 (m, 2H), 7.70 (d, J 6.9 Hz,
1H), 7.58-7.29 (m, 7H), 7.15 (d, J 9.0 Hz, 1H), 6.85 (d,
J 2.1 Hz, 1H), 6.82-6.74 (m, 2H), 5.88 (m, 1H), 3.95 (dd,
J 17.4 and 7.8 Hz, 1H), 3.79 (dd, J 17.4 and 6.3 Hz, 1H),
3.66 (s, 3H); 13C NMR (75 MHz, CDCl3) d 198.5, 153.8,
139.8, 137.1, 134.1, 133.1, 131.8, 131.5, 128.6, 128.5,
128.1, 127.1, 127.0, 126.1, 125.5, 125.3, 124.3, 123.6,
122.9, 118.8, 112.2, 111.8, 101.3; 55.8, 44.6, 33.2; IR
n
max/cm-1 (KBr) 3412 (NH), 1680 (C=O), 1484, 1212,
780; HRMS (ESI+, m/Na+) Found: 428.16208. Calc. for
C28H23O2N/Na+: 428.16210.
3-(5-Methoxy-1H-indol-3-yl)-3-(4-methoxyphenyl)-1-
phenylpropan-1-one (3x): 95%, brown solid, mp 70-71 °C;
1H NMR (300 MHz, CDCl3) d 8.02 (br s, 1H), 7.91 (d,
J 7.8Hz, 2H), 7.52 (t, J 7.8 Hz, 1H), 7.40 (t, J 7.5 Hz,
2H), 7.24 (d, J 8.7 Hz, 2H), 7.14 (d, J 8.7Hz, 1H), 6.90 (s,
1H), 6.83 (d, J 2.1 Hz, 1H), 6.77 (d, J 8.4 Hz, 3H), 4.95
(t, J 7.2 Hz, 1H), 3.81-3.61 (m, 8H); 13C NMR (75 MHz,
CDCl3) d 198.9, 157.9, 153.6, 137.1, 136.2, 133.0, 131.7,
128.7, 128.5, 128.0, 126.9, 122.1, 119.1, 113.7, 112.0,
111.8, 101.4, 55.7, 55.1, 45.2, 37.4; IR nmax/cm-1 (KBr)
3400 (NH), 2929, 1683 (C=O), 1509, 1485, 1247, 1212,
1175, 1033; HRMS (ESI+, m/ Na+) Found: 408.15689. Calc.
for C25H23O3N/Na+: 408.15702.
3-(1H-Indol-3-yl)-3-(4-methoxyphenyl)-1-phenyl-
propan-1-one (3t):64 80%, brownish solid, mp 114-115 °C;
1H NMR (300 MHz, CDCl3) d 8.00 (br s, 1H), 7.92
(d, J 7.8 Hz, 2H), 7.53 (t, J 7.5 Hz, 1H), 7.47-7.36 (m,
3H), 7.29 (d, J 7.8 Hz, 1H), 7.25 (d, J 8.4 Hz, 2H),
7.13 (t, J 7.5 Hz, 1H), 7.00 (t, J 7.5, 1H), 6.95 (d,
J 1.5 Hz, 1H), 6.78 (d, J 8.4 Hz, 2H), 5.01 (t, J 6.9 Hz, 1H),
3.83-3.63 (m, 5H); d 13C NMR (75 MHz, CDCl3,) 198.8,
157.9, 137.1, 136.6, 136.3, 133.0, 128.7, 128.5, 128.1,
126.5, 122.0, 121.3, 119.5, 119.3, 113.7, 111.1, 55.1, 45.3,
37.4; IR nmax/cm-1 (KBr) 3420 (NH), 1670 (C=O), 1510,
1249, 1177, 1031, 746.
3-(5-Methoxy-1H-indol-3-yl)-1-phenyl-3-(thiophen-
3-(1H-Indol-3-yl)-1-phenyl-3-(thiophen-2-yl)-propan-
1-one (3u):65 74%, brown solid, mp 153-154 °C; 1H NMR
(300 MHz, CDCl3) d 8.02 (br s, 1H), 7.93 (d, J 8.1 Hz,
2H), 7.53 (t, J 7.5 Hz, 2H), 7.42 (t, J 7.5 Hz, 2H), 7.31 (d,
J 8.1 Hz, 1H), 7.20-7.00 (m, 4H), 6.95-6.83 (m, 2H), 5.36
(t, J 7.2 Hz, 1H), 3.83 (d, J 7.2 Hz, 2H); 13C NMR (75 MHz,
CDCl3,) d 198.1, 148.7, 137.0, 136.5, 133.1, 128.6, 128.1,
126.5, 126.2, 124.2, 123.4, 122.2, 121.6, 119.5, 119.4,
119.0, 111.2, 46.1, 33.5; IR nmax/cm-1 (KBr) 3409 (NH),
3057, 1682 (C=O), 1268, 743, 689.
2-yl)propan-1-one (3y): 92%, pale yellow solid,
mp 153-154 °C; H NMR (300 MHz, CDCl3) d 7.98-
1
7.88 (m, 3H), 7.54 (m, 1H), 7.43 (m, 2H), 7.21 (d,
J 8.7 Hz, 1H), 7.10 (m, 1H), 7.04 (d, J 2.4 Hz, 1H), 6.95
(d, J 2.4 Hz, 1H), 6.94-6.85 (m, 2H), 6.83 (dd, J 8.7 and
2.4 Hz, 1H), 5.32 (m, 1H), 3.82-3.75 (m, 5H); 13C NMR
(75 MHz, CDCl3) d 198.1, 153.9, 148.7, 137.0, 133.1,
131.6, 128.6, 128.1, 126.7, 126.5, 124.2, 123.5, 122.3,
118.8, 112.3, 111.9, 101.3, 55.9, 46.0, 33.4; IR nmax/cm-1
(KBr) 3382 (NH), 1680 (C=O), 1485, 1438, 1213, 1171,
732; HRMS (ESI+, m/Na+) Found: 384.10283. Calc. for
C22H19O2N/Na+: 384.10287.
3-(5-Methoxy-1H-indol-3-yl)-1,3-diphenylpropan-1-
1
one (3v):66 96%, yellow solid, mp 136-137 °C; H NMR
(300 MHz, CDCl3) d 8.02 (br s, 1H), 7.92 (d, J 7.2 Hz,
2H), 7.6-7.1 (m, 9H), 6.92 (d, J 1.5 Hz, 1H), 6.85-6.73 (m,
2H), 5.00 (m, 1H), 3.84-3.64 (m, 5H); 13C NMR (75 MHz,
CDCl3) d 198.7, 153.7, 144.1, 137.1, 133.0, 131.7, 128.5,
128.4, 128.1, 127.8, 127.0, 126.2, 122.2, 118.8, 112.1,
111.8, 101.4, 55.7, 45.1, 38.2; IR nmax/cm-1 (KBr) 3366
(NH), 1679 (C=O), 1485, 1457, 1448, 1214, 1170, 723.
3-(2-Methyl-1H-indol-3-yl)-1,3-diphenylpropan-
1-one (3z):46 96%, brownish solid, mp 130-131 °C;
1H NMR (300 MHz, CDCl3) d 8.03 (br s, 1H), 7.91 (d,
J 7.5 Hz, 2H), 7.51 (t, J 7.2 Hz, 1H), 7.46-7.06 (m, 10H),
6.99 (t, J 7.2 Hz, 1H), 6.90 (s, 1H), 5.05 (m, 1H), 3.80
(dd, J 16.8 and 6.9 Hz, 1H), 3.70 (dd, J 16.8 and 7.8 Hz,
1H); 13C NMR (75 MHz, CDCl3) d 198.7, 144.2, 137.0,
136.6, 133.0, 128.5, 128.4, 128.1, 127.8, 126.5, 126.2,
122.0, 121.4, 119.4, 119.3, 119.1, 111.1, 45.2, 38.2; IR
3-(5-Methoxy-1H-indol-3-yl)-3-(naphthalen-1-yl)-1-
phenylpropan-1-one (3w): 95%, pale brown solid, mp 156-
157 °C; 1H NMR (300 MHz, CDCl3) d 8.35-8.26 (m, 1H),
n
max/cm-1 (KBr) 3411 (NH), 1681 (C=O), 1456, 1448,
745, 700.

632
Metal Halide Hydrates as Lewis Acid Catalysts for the Conjugated Friedel-Crafts Reactions of Indoles
J. Braz. Chem. Soc.
Procedure for the synthesis of nitro-adducts 5a in i-PrOH
J 12.6 and 7.5 Hz, 1H), 4.89 (dd, J 12.6 and 8.7 Hz, 1H);
13C NMR (75 MHz, CDCl3) d 162.1 (d, J 245 Hz), 136.5,
134.9 (d, J 3 Hz), 129.3 (d, J 8 Hz), 125.9, 122.8, 121.4,
120.0, 118.8, 115.8 (d, J 21 Hz), 114.2, 111.4, 79.5, 40.8;
IR nmax/cm-1 (KBr) 3371 (NH), 1542, 1508, 1430, 1378,
1224, 748.
In a 25 mL round botton flask equipped with a reflux
condenser, and magnetic stirrer was added the indole
1a (1.0 mmol), the nitroolefin 4a (1.1 mmol), and the
CoCl2·6H2O (0.1 mmol) in i-PrOH (2 mL). The reaction
mixture was heated to reflux temperature of i-PrOH and
stirredfor2h.Afterthecompletionofthereaction, monitored
by TLC, the solvent was removed under vaccum and the
crude product 5a was purified by column chromatography
usingamixtureofhexanes/ethylacetate70:30(v/v)aseluent.
4 - ( 1 - ( 1 H - I n d o l - 3 - y l ) - 2 - n i t ro e t h y l ) - N , N -
dimethylaniline (5d):68 98%, pink solid, mp 131-133 °C;
1H NMR (300 MHz, CDCl3) d 8.09 (br s, 1H); 7.46 (d,
J 8.1 Hz, 1H); 7.35 (d, J 8.1 Hz, 1H); 7.24-7.00 (m, 5H);
6.71 (d, J 8.4 Hz, 2H); 5.10 (m, 1H); 5.03 (dd, J 11.7 and
7.5 Hz, 1H); 4.88 (dd, J 11.7 and 8.4 Hz, 1H); 2.92 (s,
6H); 13C NMR (75 MHz, CDCl3) d 149.8; 136.5; 128.4;
126.7; 126.2; 122.5; 121.4; 119.8; 119.1; 115.1; 112.7;
111.3; 79.9; 40.8; 40.5; IR nmax/cm-1 (KBr) 3434 (NH),
2916, 1611, 1519, 1379, 817, 743.
3-(2-Nitro-1-phenylethyl)-1H-indole (5a):62 97%,
brownish solid, mp 99-100 °C; 1H NMR (300 MHz, CDCl3)
d 7.84 (br s, 1H), 7.37 (d, J 8.1 Hz, 1H), 7.25-7.05 (m, 7H),
7.00 (t, J 7.2 Hz, 1H), 6.72 (d, J 1.8 Hz, 1H), 5.08 (m, 1H),
4.87 (dd, J 12.3 and 7.5 Hz, 1H), 4.76 (dd, J 12.3 and 8.4
Hz, 1H); 13C NMR (75 MHz, CDCl3) d 139.1, 136.2, 128.7,
127.6, 127.3, 125.8, 122.3, 121.5, 119.6, 118.6, 113.7,
111.3, 79.3, 41.3; IR nmax/cm-1 (KBr) 3401 (NH), 3052,
1536, 1455, 1424, 1377, 1097, 750, 704.
3-(1-(3,4-Dimethoxyphenyl)-2-nitroethyl)-1H-indole
o
1
(5e):69 90%, orange solid, mp 79-80 C; H NMR
(300 MHz, CDCl3) d 8.27 (br s, 1H), 7.43 (d, J 7.8 Hz,
1H), 7.28 (d, J 8.1 Hz, 1H), 7.16 (t, J 7.5 Hz, 1H), 7.05
(t, J 7.5 Hz, 1H), 6.93 (s, 1H), 6.87-6.80 (m, 2H), 6.76 (d,
J 8.1 Hz, 1H), 5.11 (m, 1H), 5.00 (dd, J 12.3 and 7.5 Hz,
1H), 4.87 (dd, J 12.3 and 8.4 Hz, 1H), 3.79 (s, 3H), 3.76
(s, 3H); 13C NMR (75 MHz, CDCl3) d 149.0, 148.2, 136.4,
131.7, 125.9, 122.4, 121.5, 119.7, 119.6, 118.7, 114.2,
111.4, 111.3, 111.1, 79.6, 55.7, 41.1; IR nmax/cm-1 (KBr)
3405 (NH), 1549, 1515, 1262, 1141, 1023, 745.
General procedure for the synthesis of nitro-adducts 5b-q
under solventless conditions
In a 25 mL round-botton flask equiped with a reflux
condenser, and magnetic stirrer, were added the indoles
1a-c (1.0 mmol), the nitroolefins 4b-g (1.1 mmol) and
CoCl2·6H2O (0.1 mmol). The reactional flask was placed
in a 100 °C pre-heated silicone oil bath and was stirred
for the appropriate time showed in the Table 6. After the
completion of the reaction, monitored by TLC, the crude
product 5b-q were purified by column chromatography
using a mixture of hexanes/ethyl acetate.
3-(1-(Naphthalen-1-yl)-2-nitroethyl)-1H-indole (5f):67
97%, redish solid, mp 140-142 °C; 1H NMR (300 MHz,
CDCl3) d 8.27 (d, J 8.4 Hz), 8.05 (br s, 1H, NH), 7.91-
7.86 (m, 1H), 7.82-7.74 (m, 1H), 7.59-7.32 (m, 6H), 7.23-
7.15 (m, 1H), 7.09-6.97 (m, 2H), 6.07 (m, 1H), 5.12 (dd,
J 12.9 and 8.1 Hz, 1H), 5.07 (dd, J 12.9 and 7.2 Hz, 1H);
13C NMR (75 MHz, CDCl3) d 136.6, 134.6, 134.2, 131.1,
129.1, 128.3, 126.8, 126.1, 125.9, 125.3, 124.6, 122.7,
122.6, 120.0, 118.8, 114.3, 111.4, 78.5, 37.0; IR nmax/cm-1
(KBr) 3420 (NH), 1545, 1509, 1458, 1381, 796, 777, 743.
3-(1-(4-Methoxyphenyl)-2-nitroethyl)-1H-indole (5b):67
92%, brownish solid, mp 146-147 °C; 1H NMR (300 MHz,
CDCl3) d 8.10 (br s, 1H), 7.43 (d, J 8.1 Hz, 1H), 7.35 (d,
J 8.1 Hz, 1H), 7.24 (d, J 8.4 Hz, 2H), 7.19 (t, J 7.5 Hz,
1H), 7.07 (t, J 7.5 Hz, 1H), 7.01 (d, J 1.5 Hz, 1H), 6.84 (d,
J 8.4 Hz, 2H), 5.14 (m, 1H), 5.04 (dd, J 12.3 and 7.5 Hz,
1H), 4.89 (dd, J 12.3 and 8.4 Hz, 1H), 3.77 (s, 3H);
13C NMR (75 MHz, CDCl3) d 158.8, 136.5, 131.2, 128.8,
126.1, 122.6, 121.4, 119.9, 119.0, 114.8, 114.3, 111.3, 79.7,
55.2, 40.8; IR nmax/cm-1 (KBr) 3379 (NH), 1547, 1511,
1463, 1422, 1377, 1245, 1029, 750.
3-(2-Nitro-1-(thiophen-2-yl)ethyl)-1H-indole (5g):69
1
98%, brown solid, mp 86-87 °C; H NMR (300 MHz,
CDCl3) d 8.03 (br s, 1H), 7.49 (d, J 8.1 Hz, 1H), 7.29
(d, J 8.1 Hz, 1H), 7.22-7.05 (m, 3H), 6.98 (d, J 2.7 Hz,
1H), 6.96-6.87 (m, 2H), 5.42 (m, J 7.8 Hz, 1H), 4.99 (dd,
J 12.3 and 8.1 Hz, 1H), 4.92 (dd, J 12.3 and 8.1 Hz, 1H);
13C NMR (75 MHz, CDCl3) d 142.8, 136.2, 126.9, 125.5,
125.1, 124.8, 122.5, 121.9, 119.9, 118.6, 113.6, 111.5,
79.8, 36.7; IR nmax/cm-1 (KBr) 3416 (NH), 1550, 1455,
1433, 1418, 1377, 747, 720.
3-(1-(4-Fluorophenyl)-2-nitroethyl)-1H-indole (5c):67
1
97%, orange solid, mp 77-78 °C; H NMR (300 MHz,
CDCl3) d 8.10 (br s, 1H), 7.39 (d, J 7.8 Hz, 1H), 7.37-
7.16 (m, 4H), 7.11-6.95 (m, 4H), 5.16 (m, 1H), 5.04 (dd,

Vol. 22, No. 4, 2011
Schwalm et al.
633
5-Methoxy-3-(2-nitro-1-phenylethyl)-1H-indole (5h):67
95%, brownish solid, mp 130-131 °C; 1H NMR (300 MHz,
CDCl3) d 8.02 (br s, 1H), 7.32-7.15 (m, 6H), 6.93 (s, 1H),
6.86-6.80 (m, 2H), 5.11 (m, 1H), 5.00 (dd, J 12.3 and
7.5 Hz, 1H), 4.89 (dd, J 12.3 and 8.4 Hz, 1H), 3.75 (s, 3H);
13C NMR (75 MHz, CDCl3) d 154.0, 139.1, 131.5, 128.8,
127.7, 127.5, 126.5, 122.3, 113.9, 112.6, 112.1, 100.7, 79.4,
55.8, 41.4; IR nmax/cm-1 (KBr) 3447 (NH), 1548, 1482,
1453, 1440, 1379, 1209, 1177.
CDCl3) d 153.9, 149.0, 148.1, 131.6, 131.5, 126.4, 122.2,
119.6, 113.8, 112.3, 112.1, 111.2, 111.1, 100.7, 79.5, 55.7,
55.7, 55.6, 41.1; IR nmax/cm-1 (KBr) 3436 (NH), 2955,
2931, 2830, 1544, 1510, 1259, 1020. HRMS (ESI+, m/Na+)
Found: 379.12635. Calc. for C19H20O5N2/Na+: 379.12644.
5-Methoxy-3-(1-(naphthalen-1-yl)-2-nitroethyl)-1H-
1
indole (5m): 98%, brown solid, mp 76-77 °C. H NMR
(300 MHz, CDCl3) d 8.25 (d, J 8.1 Hz, 1H), 7.97 (br s, 1H),
7.92-7.74 (m, 2H), 7.58-7.17 (m, 5H), 6.95-6.81 (m, 3H),
6.00 (t, J 7.8 Hz, 1H), 5.08 (d, J 7.8 Hz, 2H), 3.71 (s, 3H);
13C NMR (75 MHz, CDCl3) d 154.2, 134.6, 134.2, 131.7,
131.2, 129.1, 128.3, 126.8, 126.6, 125.9, 125.3, 124.5,
123.3, 122.7, 114.0, 112.7, 112.1, 100.7, 78.5, 55.8, 37.0;
IR nmax/cm-1 (KBr) 3420 (NH), 1549, 1484, 1457, 1437,
1376, 1213, 800.
5-Methoxy-3-(1-(4-methoxyphenyl)-2-nitroethyl)-1H-
indole (5i): 86%, pale yellow solid, mp 141-142 °C; 1H NMR
(300 MHz, CDCl3) d 8.00 (br s, 1H), 7.28-7.21 (m, 3H), 6.99
(d, J 2.1 Hz, 1H), 6.88-6.82 (m, 4H), 5.09 (m, 1H), 5.02 (dd,
J 11.7 and 7.2 Hz, 1H), 4.88 (dd, J 11.7 and 7.8 Hz, 1H),
13
3.77 (s, 6H); C NMR (75 MHz, CDCl3) d 158.9, 154.2,
131.6, 131.1, 128.8, 126.6, 122.1, 114.4, 114.3, 112.7, 112.1,
100.9, 79.7, 55.8, 55.2, 40.8; IR nmax/cm-1 (KBr) 3434 (NH),
2959, 1545, 1513, 1480, 1456, 1247, 1208.
5-Methoxy-3-(2-nitro-1-(thiophen-2-yl)ethyl)-1H-
indole (5n): 93%, greenish brown solid, mp 83-85 °C;
1H NMR (300 MHz, CDCl3) d 8.15 (br s, 1H), 7.26-7.20
(m, 2H), 7.06-6.89 (m, 5H), 5.45 (m, 1H), 5.04 (dd,
J 12.6 and 7.5 Hz, 1H), 4.99 (dd, J 12.6 and 8.1 Hz,
1H), 3.85 (s, 3H); 13C NMR (75 MHz, CDCl3) d 154.1,
142.9, 131.4, 126.9, 126.1, 125.1, 124.8, 113.5, 112.6,
112.2, 100.6, 79.9, 55.8, 36.8; IR nmax/cm-1 (KBr) 3336
(NH), 2929, 2829, 1551, 1489, 1436, 1376, 1214, 716;
HRMS (ESI+, m/ Na+) Found: 325.06167. Calc. for
C15H14O3N2S/Na+: 325.06174.
3-(1-(4-Fluorophenyl)-2-nitroethyl)-5-methoxy-1H-
indole (5j): 96%, brown solid, mp 102-103 °C; 1H NMR
(300 MHz, CDCl3) d 8.11 (br s, 1H); 7.28-7.20 (m, 2H),
7.17 (d, J 8.7 Hz, 1H), 7.00-6.88 (m, 3H), 6.83 (dd, J 8.7
and 2.4 Hz, 1H), 6.78 (d, J 2.1 Hz, 1H), 5.08 (m, 1H), 4.97
(dd, J 12.3 and 7.5 Hz, 1H), 4.83 (dd, J 12.3 and 8.4 Hz,
1H), 3.74 (s, 3H); 13C NMR (75 MHz, CDCl3) d 161.9 (d,
J 2.4 Hz), 154.0, 134.8 (d, J 3 Hz), 131.5, 129.3 (d, J 8 Hz),
126.3, 122.1, 115.7 (d, J 21 Hz), 113.6, 112.6, 112.2, 100.7,
79.4, 55.7, 40.7; IR nmax/cm-1 (KBr) 3434 (NH), 1551, 1509,
1482, 1454, 1439, 1377, 1226, 1207, 808.
2-Methyl-3-(2-nitro-1-phenylethyl)-1H-indole (5o):67
94%, pale pink solid, mp 102-103 °C; 1H NMR (300 MHz,
CDCl3) d 7.80 (br s, 1H), 7.35 (d, J 7.8 Hz, 1H), 7.32-7.16
(m, 6H), 7.08 (m, 1H), 7.00 (m, 1H), 5.23-5.04 (m, 3H),
2.28 (s, 3H); 13C NMR (75 MHz, CDCl3) d 139.5, 135.3,
132.8, 128.7; 127.2, 127.0, 126.8, 121.2, 119.6, 118.5,
110.7, 108.7, 78.6, 40.4, 11.8; IR nmax/cm-1 (KBr) 3403
(NH), 1550, 1459, 1428, 1377, 743, 700.
4-(1-(5-Methoxy-1H-indol-3-yl)-2-nitroethyl)-N,N-
dimethylaniline (5k): 87%, pink solid, mp 134-135 °C;
1H NMR (300 MHz, CDCl3) d 7.99 (br s, 1H), 7.23 (d,
J 8.1 Hz, 1H), 7.21-7.14 (m, 2H), 6.96 (d, J 2.4 Hz,
1H), 6.87 (d, J 2.4 Hz, 1H), 6.83 (dd, J 8.7 and 2.4 Hz,
1H), 6.68 (d, J 9 Hz, 2H), 5.07-4.95 (m, 2H), 4.92-4.80
(m, 1H), 3.77 (s, 3H), 2.90 (s, 6H); 13C NMR (75 MHz,
CDCl3) d 154.0, 149.7, 131.6, 128.4, 126.9, 126.6, 122.2,
114.7, 112.9, 112.5, 112.0, 101.0, 79.8, 55.8, 40.7, 40.6;
IR nmax/cm-1 (KBr) 3408 (NH), 1616, 1541, 1524, 1484,
1376, 1210, 1201. HRMS (ESI+) Found: 340.16545.
Calc. for C19H21O3N3: 340.16557.
2-Methyl-3-(1-(naphthalen-1-yl)-2-nitroethyl)-1H-
indole (5p): 94%, pale yellow solid, mp 150-151 °C;
1H NMR (300 MHz, CDCl3) d 8.11 (m, 1H), 7.89-7.82
(m, 2H), 7.79 (d, J 8.1 Hz, 1H), 7.60 (d, J 7.2 Hz, 1H),
7.55 (d, J 7.2 Hz, 1H), 7.52-7.39 (m, 3H), 7.28-7.21 (m,
1H), 7.15-7.03 (m, 2H), 5.92 (m, 1H), 5.25 (dd, J 12.9 and
6.9 Hz, 1H), 5.19 (dd, J 12.9 and 8.7 Hz, 1H), 2.27 (s, 3H);
13C NMR (75 MHz, CDCl3) d 135.3, 134.5, 134.1, 132.9,
131.3, 129.1, 128.3, 127.3, 126.6, 125.8, 125.1, 124.3,
123.0, 121.4, 119.8, 118.4, 110.7, 108.3, 78.0, 37.4, 12.3;
IR nmax/cm-1 (KBr) 3415, 3348, 2921, 2870, 1453, 903,
742; HRMS (ESI+, m/Na+) Found: 353.12611. Calc.for
C21H18O2N2/Na+: 353.12605.
3-(1-(3,4-Dimethoxyphenyl)-2-nitroethyl)-5-methoxy-
1H-indole (5l): 98%, brownish solid, mp 131-132 °C;
1H NMR (300 MHz, CDCl3) d 8.31 (br s, 1H), 7.15 (d,
J 8.7 Hz, 1H), 6.94-6.74 (m, 6H), 5.06 (m, 1H), 4.98 (dd,
J 11.7 and 7.2 Hz, 1H), 4.86 (dd, J 11.7 and 8.4 Hz, 1H),
3.79 (s, 3H), 3.76 (s, 3H), 3.75 (s, 3H); 13C NMR (75 MHz,

634
Metal Halide Hydrates as Lewis Acid Catalysts for the Conjugated Friedel-Crafts Reactions of Indoles
J. Braz. Chem. Soc.
2-Methyl-3-(2-nitro-1-(thiophen-2-yl)ethyl)-1H-indole
filtered and the solvent evaporated under vacuum. The 1H
NMR analysis of the crude product showed a mixture of
two diastereoisomers in 87:13 ratio. The 1,4-trans relative
configuration for the major isomer was assumed based on
literature data. The crude product was purified by column
chromatography using a mixture of hexanes/ethyl acetate
75:25 (v/v) as eluent. After purification only the major
isomer was observed in the 1H NMR spectra.
1
(5q): 98%, greenish brown solid, mp 89-91 °C H NMR
(300 MHz, CDCl3) d 7.75 (br s, 1H); 7.32 (d, J 7.8 Hz,
1H), 7.16-6.95 (m, 4H), 6.87-6.80 (m, 2H), 5.29 (dd, J 9.0
and 6.6 Hz, 1H), 5.10 (dd, J 12.3 and 6.6 Hz, 1H), 4.99
(dd, J 12.3 and 9.0 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 143.2, 135.2, 133.0, 126.7, 126.1, 124.6, 124.2, 121.1,
119.5, 118.4, 110.7, 108.1, 78.7, 36.4, 11.4; IR nmax/cm-1
(neat, film) 3404 (NH), 1551, 1460, 1427, 1378, 745,
702; HRMS (ESI+, m/Na+) Found: 309.06671. Calc. for
C15H14O2N2S/Na+: 309.06682.
trans-1,4-Diphenyl-2,3,4,9-tetrahydro-1H-
pyrido[3,4-b] indole (9-trans):59 70%, pale brown solid,
mp 184-185 °C; 1H NMR (300 MHz, CDCl3) d 7.70 (br s,
1H), 7.40-7.21 (m, 10 H), 7.18 (d, J 8.1 Hz, 1H), 7.06 (m,
1H), 6.90-6.78 (m, 2H), 5.25 (s, 1H), 4.37 (m, 1H), 3.53
(dd, J 12.6 and 5.1 Hz, 1H), 3.02 (dd, J 12.6 and 8.7 Hz,
1H), 1.91 (br s, 1H); 13C NMR (75 MHz, CDCl3) d 143.0,
141.4, 135.9, 135.8, 128.9, 128.6, 128.4, 128.3, 126.7,
126.5, 121.5, 119.8, 119.3, 112.5, 110.7, 58.2, 52.9, 41.7;
IR nmax/cm-1 (KBr) 3405, 3319, 3052, 3019, 2952, 2811,
1451, 1273, 750, 697.
Preparation of the triptamine derivative 8
To a stirred solution of compound 5a (266.3 mg,
1 mmol) in CH3OH (5 mL) were sequentially added Pd/C
10% (52mg) and HCOONH4 (315.3 mg, 5 mmol). The
reaction mixture was stirred at room temperature overnight.
The reaction mixture was filtered on a celite pad, washed
several times with CH3OH and the solvent removed on
a rotatory evaporator. To the white residue was added
saturated Na2CO3(aq) until pH 8 was reached and then
the aqueous mixture was extracted twice with EtOAc.
The combined organic phases were dried over MgSO4,
filtered and the solvent removed under vacuum, affording
compound 8. The crude product was used in the next step
without further purification.
Supplementary Information
1
The spectroscopic H NMR, 13C NMR, IR data as
well as the HRMS of selected compounds are provided as
supplementary information and available free of charge at
http:// jbcs.sbq.org.br, as PDF file.
2-(1H-Indol-3-yl)-2-phenylethanamine (8):58 90%, pale
brown solid, mp 129-130 °C. 1H NMR (300 MHz, CDCl3)
d 8.33 (br s, 1H), 7.45 (d, J 7.8 Hz, 1H), 7.35-7.10 (m, 7H),
7.02 (t, J 7.5 Hz, 2H), 4.25 (m, 1H), 3.42 (dd, J 12.6 and
7.2 Hz, 1H), 3.27 (dd, J 12.6 and 7.8 Hz, 1H), 1.71 (br s,
2H); 13C NMR (75 MHz, CDCl3) d 142.9, 136.5, 128.5,
128.1, 127.0, 126.4, 122.1, 121.3, 119.4, 119.3, 117.4,
111.1, 47.1, 46.7; IR nmax/cm-1 (KBr) 3415, 3348, 2921,
2870, 1453, 903, 742.
Acknowledgments
The authors thank the Conselho Nacional de
Desenvolvimento Científico e Tecnológico (CNPq)
for the financial support (D. R., Grant Universal
No.484615/2007-6).C.S.S.acknowledgestheCoordenação
deAperfeiçoamento de Pessoal de Nível Superior (CAPES)
for the graduate fellowship. We would like to thank Prof.
Dr. Marcos N. Eberlin and MSc Clécio F. Klitzke from
the Thomson Mass Spectrometry Laboratory of Instituto
de Química-UNICAMP, for the HRMS analysis, and also
Prof. Dr. Luiz Carlos Dias for his generosity reading and
suggesting improvements to this work.
Preparation of b-carboline derivative 9
To a suspension of MgSO4 (240 mg) and compound
8 (70.9 mg, 0.3 mmol) in CH2Cl2 (2 mL) was added
benzaldehyde (37 mL, 0.36 mmol, 1.2 equiv.) at room
temperature and the mixture was stirred at room temperature
for 1 h. The suspension was cooled to 0 °C and TFA (45 mL
0.6 mmol, 2.0 equiv.) was slowly added. The reaction
was stirred at room temperature for 72 h. The reaction
was quenched by addition of sat. NaHCO3 at 0 °C until
pH 8 was reached. After filtration over celite, the filtrate
was extracted with CH2Cl2. The combined organic layers
were washed with brine, dried over anhydrous MgSO4,
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Submitted: July 31, 2010
Published online: November 23, 2010

J. Braz. Chem. Soc., Vol. 22, No. 4, S1-S35, 2011.
Printed in Brazil - ©2011 Sociedade Brasileira de Química
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Supplementary Information
SI
Metal Halide Hydrates as Lewis Acid Catalysts for the Conjugated Friedel-Crafts
Reactions of Indoles and Activated Olefins
Cristiane S. Schwalm, Marco Antonio Ceschi and Dennis Russowsky*
Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500,
91501-970 Porto Alegre-RS, Brazil
Figure S1. 1H NMR (CDCl3) of compound 3f.
*e-mail: dennis@iq.ufrgs.br

S2
Metal Halide Hydrates as Lewis Acid Catalysts for the Conjugated Friedel-Crafts Reactions
J. Braz. Chem. Soc.
Figure S2. 13C NMR (CDCl3) of compound 3f.
Figure S3. IR (neat) of compound 3f.

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Figure S4. 1H NMR (CDCl3) of compound 3g
Figure S5. 13C NMR (CDCl3) of compound 3g

S4
Metal Halide Hydrates as Lewis Acid Catalysts for the Conjugated Friedel-Crafts Reactions
J. Braz. Chem. Soc.
Figure S6. IR (KBr) of compound 3g.
Figure S7. 1H NMR (CDCl3) of compound 3i.

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Figure S8. 13C NMR (CDCl3) of compound 3i
Figure S9. IR (neat) of compound 3i.

S6
Metal Halide Hydrates as Lewis Acid Catalysts for the Conjugated Friedel-Crafts Reactions
J. Braz. Chem. Soc.
Figure S10. 1H NMR (CDCl3) of compound 3k.
Figure S11. 13C NMR (CDCl3) of compound 3k.

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Figure S12. IR (neat) of compound 3k.
Figure S13. 1H NMR (CDCl3) of compound 3l.

S8
Metal Halide Hydrates as Lewis Acid Catalysts for the Conjugated Friedel-Crafts Reactions
J. Braz. Chem. Soc.
Figure S14. 13C NMR (CDCl3) of compound 3l.
Figure S15. IR (neat) of compound 3l.

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Figure S16. 1H NMR (CDCl3) of compound 3s.
Figure S17. 13C NMR (CDCl3) of compound 3s.

S10
Metal Halide Hydrates as Lewis Acid Catalysts for the Conjugated Friedel-Crafts Reactions
J. Braz. Chem. Soc.
Figure S18. IR (KBr) of compound 3s.
Figure S19. 1H NMR (CDCl3) of compound 3w.

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Figure S20. 13C NMR (CDCl3) of compound 3w.
Figure S21. IR (KBr) of compound 3w.

S12
Metal Halide Hydrates as Lewis Acid Catalysts for the Conjugated Friedel-Crafts Reactions
J. Braz. Chem. Soc.
Figure S22.1H NMR (CDCl3) of compound 3x.
Figure S23. 13C NMR (CDCl3) of compound 3x.

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Figure S24. IR (KBr) of compound 3x.
Figure S25. 1H NMR (CDCl3) of compound 3y.

S14
Metal Halide Hydrates as Lewis Acid Catalysts for the Conjugated Friedel-Crafts Reactions
J. Braz. Chem. Soc.
Figure S26. 13C NMR (CDCl3) of compound 3y.
Figure S27. IR (KBr) of compound 3y.

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Figure S28. 1H NMR (CDCl3) of compound 5i.
Figure S29. 13C NMR (CDCl3) of compound 5i.

S16
Metal Halide Hydrates as Lewis Acid Catalysts for the Conjugated Friedel-Crafts Reactions
J. Braz. Chem. Soc.
Figure S30. IR (KBr) of compound 5i.
Figure S31. 1H NMR (CDCl3) of compound 5j.