Microwave-assisted solid-acid-catalyzed friedel-crafts alkylation and electrophilic annulation of indoles using alcohols as alkylating agents

Article abstract of DOI:10.1055/s-0029-1217052

Alcohols are considered environmentally benign alkylating agents since the only by-product generated in their reactions is water. Herein, we report a microwave-assisted Friedel-Crafts alkylation and electrophilic annulation of indoles using alcohols as al

Full text of DOI:10.1055/s-0029-1217052

4010
PAPER
Microwave-Assisted Solid-Acid-Catalyzed Friedel–Crafts Alkylation and
Electrophilic Annulation of Indoles Using Alcohols as Alkylating Agents
M
icrowave-Assist
d
e
d
Friedel–C
i
rafts
A
t
lkylatio
y
n/Annulatio
a
n of Indoles Kulkarni, Phong Quang, Béla Török*
Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd., Boston, MA 02125, USA
Fax +1(617)2876030; E-mail: bela.torok@umb.edu
Received 29 April 2009; revised 29 July 2009
The application of solid-acid catalysis to replace harmful
Abstract: Alcohols are considered environmentally benign alkylat-
ing agents since the only by-product generated in their reactions is
water. Herein, we report a microwave-assisted Friedel–Crafts alky-
lation and electrophilic annulation of indoles using alcohols as alky-
mineral acids is a rapidly growing area in organic synthe-
sis. Solid acids such as natural or modified clays, metal
oxides, zeolites, acidic ion-exchange resins have been
lating agents. Alkylation of indoles using tert-butyl alcohol gives 3- widely explored to develop greener synthetic methods.7
substituted tert-butylindoles. A domino electrophilic annulation/
Friedel–Crafts alkylations using alcohols as electrophiles
aromatization of indoles using hexane-2,5-diol results in the forma-
have also been reported with solid-acid catalysts such as
tion of substituted carbazoles. The reaction is catalyzed by a strong,
modified K-108 and anionic clays.9 The catalyst of choice
solid-acid catalyst montmorillonite K-10. The products were ob-
in this work is montmorillonite K-10. It offers a range of
tained in good yields and high selectivities.
advantages over liquid acids. It is a noncorrosive, inex-
Key words: alkylation, carbazoles, indole, tert-butyl alcohol, hex-
pensive, and easily reusable stable solid. Most important-
ane-2,5-diol, montmorillonite K-10, microwave heating, annulation
ly, it is commercially available and can be used without
any pretreatment. These benefits along with physical
characterization of K-10 have been discussed in several
The indole scaffold is prominent among numerous natural
reviews.6,7,10 It is also an excellent catalyst for microwave-
products and biologically active compounds.1 Therefore,
assisted organic synthesis (MAOS).10
synthesis and functionalization of indoles have attracted
considerable attention over the years.2 The Friedel–Crafts
alkylation is extensively used in the chemical industry to
produce a vast array of products.3 It is one of the most fun-
damental C–C bond-forming reactions and has been ex-
plored widely for the functionalization of indoles.4,5
Although very effective, the traditional Friedel–Crafts
chemistry does not conform to the ever stricter contempo-
rary environmental regulations. Thus, the design and de-
velopment of eco-friendly methods for such
transformations is of paramount importance.6 There are
numerous studies, which address the role of the catalyst,
and describe the use of environmentally benign, solid
Brønsted or Lewis acid catalysts.6 The majority of these
studies still rely on popular alkyl halides as alkylating
agents. These reactants, while very reactive and conve-
nient to use, produce corrosive and harmful hydrogen ha-
logenides as by-products and thus cannot be considered as
sustainable reagents. To replace these alkylating agents in
the design of eco-friendly processes, one can consider al-
ternatives. While alcohols are less reactive than alkyl ha-
lides in electrophilic substitutions, they have a long shelf-
life and produce water as the only by-product after alkyla-
tion. Recently, a few methods have been reported for
alkylation of indoles using alcohols.5 However, the use of
expensive, toxic, nonrecyclable, or moisture-sensitive re-
agents and catalysts does not make these methods attrac-
tive for large-scale synthesis.
In order to continue our efforts towards developing green-
er protocols for synthesis, herein we report the application
of alcohols as alkylating agents in a solid-acid-catalyzed
Friedel–Crafts alkylation of indoles (Scheme 1). The re-
actions were carried out in a CEM Discover microwave
reactor and, for comparison, in a pressure vessel under
conventional heating. The reaction of indole and tert-bu-
tyl alcohol under solvent-free conditions11 served as a
probe. Optimization reactions were carried out to study
the effect of catalyst, temperature and time. The results
are presented in Table 1. Initial results indicated that high-
er molar amount (1.5 equiv) of tert-butyl alcohol gave op-
timum yields. The reaction could be completed under
mild conditions in a matter of minutes. We have observed
the formation of two major products; the expected 3-sub-
stituted product 1 and 1,3-disubstituted indole 2. The best
selectivity for product 1 was observed at 130 °C after 10
minutes (Table 1, entry 2). Both longer reaction times and
higher temperatures increased the formation of the 1,3-di-
alkylated product 2 (entries 3, 4, and 5). Different acid-
t-Bu
R
t-BuOH
N
R
H
K-10
MW
N
H
R
hexane-2,5-diol
N
SYNTHESIS 2009, No. 23, pp 4010–4014
x
x.
x
x
.
2
0
0
9
H
Advanced online publication: 19.10.2009
DOI: 10.1055/s-0029-1217052; Art ID: M02409SS
© Georg Thieme Verlag Stuttgart · New York
Scheme 1 Montmorillonite K-10 catalyzed Friedel–Crafts alkyla-
tion of indoles using tert-butyl alcohol and hexane-2,5-diol

PAPER
Microwave-Assisted Friedel–Crafts Alkylation/Annulation of Indoles
4011
Table 2 Microwave-Assisted Alkylation of Indolesa
Table 1 Effect of Experimental Variables on the Alkylation of In-
dole Using tert-Butyl Alcohola
R1
R1
t-Bu
t-Bu
K-10
MW
t-Bu
t-BuOH
+
catalyst
N
N
N
H
N
+
H
H
MW
N
H
t-Bu
+
1
t-BuOH
1
2
Entry
R1
Temp (°C) Time (min) Yield (%)b,c
Entry Catalyst
Conditions Temp
(°C)
Time Yield
(min) (%)b 1/2
1
2
3
4
5
6
7
8
H
130
130
130
130
130
130
130
130
10
10
10
15
15
10
8
86/62
91/68
85/73
77/63
78/67
67/50
68/52
66/47
1
2
3
4
5
6
7
8
9
K-10
K-10
K-10
K-10
K-10
MWc
MWc
MWc
MWc
MWc
MWc
MWc
CHd
120
130
130
140
150
130
130
130
80
10
10
15
10
10
10
10
60
60
35/0
Cl
86/7
NO2
CN
80/15
62/31
42/55
3/10
CO2Me
OMe
OH
H3[PW12O40]
H3[PMo12O40]
K-10
10/0
Me
8
a Indole (1 mmol) and t-BuOH (1.5 mmol) were used.
36/25
34/53
b GC yields.
HCl
CHd
c Isolated yields.
a Indole (1 mmol) and t-BuOH (1.5 mmol) were used.
b GC yields.
pounds. In the intramolecular pathway, the reacting moi-
eties can undergo cyclization due to the closed spatial
arrangement. On the contrary, in intermolecular reactions,
the bidentate nature of electrophiles may lead to side reac-
tions. However, the substantially higher reactivity of N-
heterocycles such as indoles make the use of a bifunction-
al electrophile appealing.
c Microwave heating.
d Conventional heating.
catalysts were screened (entries 6, 7, and 9) and K-10 was
found to show the best performance in the alkylation of in-
dole. To determine the beneficial effect of microwaves, a
reaction under conventional heating conditions was also
carried out. Conventional heating resulted in significantly
longer reaction time at 130 °C with reduced yield and se-
lectivity (entry 8).
Our previous investigations have shown that electrophilic
annulation can be used to build indoles or carbazoles in
one-pot domino reactions.12 Carbazoles, which are ubi-
quitous in biologically active natural products13 and mate-
rial science,14 have been a target of interest for synthetic
chemists.12,15
To explore the scope of our approach, we used a variety
of substituted indoles. Table 2 summarizes the results of
the tert-butylation reactions. Almost all indoles gave the
corresponding alkylated products in good yields. It is
worth mentioning that the conversion of the starting ma-
terials is close to complete and the decrease in yield is usu-
ally due to the formation of the dialkylated products.
Indoles with electron-withdrawing groups gave better
yields as compared to those with electron-donating
groups. This behavior can be accounted for by the fact that
the first alkylation significantly increases the already high
reactivity of indoles and therefore indoles with electron-
donating groups readily undergo a second alkylation un-
like those with electron-withdrawing groups. Reaction
times were further optimized in the case of some indoles
(Table 2, entries 4, 5, 7, and 8).
To explore the possibility of the use of a diol as an alky-
lating agent, the reaction of indole and hexane-2,5-diol
was tested under the previously optimized conditions (130
°C, 10 min). The results are summarized in Table 3. How-
ever, no reaction was observed under these experimental
conditions most likely due to the lower reactivity of sec-
ondary alcohol as compared to tertiary alcohol. Upon
increasing the temperature, the formation of tetrahydro-
carbazole 3 was observed at 140 °C. Interestingly, the ar-
omatic product 4 also formed in 11% yield.
While the oxidative aromatization via dehydrogenation in
the presence of K-1016 is not unprecedented, it raised the
opportunity to synthesize carbazoles in a one-pot domino
approach. The best selectivity for the formation of carba-
zole was observed at 160 °C (Table 3, entry 4). Further in-
crease in temperature resulted in decomposition of the
product even at reduced reaction time (entry 5). For com-
parison, the test reaction was also carried out without sol-
vent in a pressure vessel by conventional heating. As
The fact that first alkylation increases the reactivity of in-
doles triggered the possibility of using a diol, which can
act as a bifunctional electrophile. Intermolecular or in-
tramolecular Friedel–Crafts cyclizations with bidentate
electrophiles can lead to biologically important com-
Synthesis 2009, No. 23, 4010–4014 © Thieme Stuttgart · New York

4012
A. Kulkarni et al.
PAPER
Table 3 Effect of Experimental Variables on the Synthesis of 1,4-
Table 4 Microwave-Assisted Synthesis of Substituted Carbazolesa
Dimethylcarbazolea
R2
R2
OH
OH
K-10
R3
R3
+
+
MW
N
R1
N
N
R1
OH
N
OH
H
H
4
4
Entry
R1
R2
R3
Temp
(°C)
Time Yield
(h)
(%)b,c
96/83
83/72
65/52
78/68
77/70
87/79
82/75
71/59
70/62
cat.
MW
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
H
Me
H
H
H
H
Me
H
H
H
H
H
160
160
160
170
160
170
160
160
170
1
N
H
Cl
1
3
Br
1
Entry
Catalyst
Conditions Temp
(°C)
Time
(h)
Yield
H
0.5
1
(%)b 3/4
Me
CO2Me
NO2
OMe
H
1
2
3
4
5
6
K-10
K-10
K-10
K-10
K-10
K-10
MWc
MWc
MWc
MWc
MWc
CHd
130
140
150
160
170
160
1
1
0/0
0.5
1
82/11
22/63
0/96
1
1
1
0.5
0.5
16
0/82
a Indole (1 mmol) and hexane-2,5-diol (1.5 mmol) were used.
b GC yields.
22/56
c Isolated yields.
a Indole (1 mmol) and hexane-2,5-diol (1.5 mmol) were used.
b GC yields.
c Microwave heating.
last step the tetrahydrocarbazole intermediate underwent
an oxidative aromatization producing the corresponding
carbazole.
d Conventional heating.
expected, even after 16 hours of heating, the formation of
carbazole was only 56% (entry 6).
In conclusion, we have successfully applied alcohols as
alkylating agents in the Friedel–Crafts alkylation of in-
doles. The K-10 catalyzed, microwave-assisted method
provides products in good yields and high selectivities in
short reaction times as compared to conventional heating.
The approach was also extended to the synthesis of di-
methylcarbazoles by a domino reaction of indole and hex-
ane-2,5-diol. Solid-acid catalysis, use of diol as an
alkylating agent, and microwave-assisted synthesis make
the approach attractive for environmentally benign syn-
thesis design.
We decided to test the scope of our approach by applying
a variety of substituted indoles. The results are tabulated
in Table 4. Various substituted indoles readily underwent
annulation/oxidative aromatization with hexane-2,5-diol
to form corresponding dimethylcarbazoles. As indicated,
the reaction conditions can tolerate various functional
groups such as alkyl, alkoxy, carbmethoxy, nitro and
halogens. 6-Methyl, 5-carboxymethyl, and N-methylin-
doles required higher reaction temperature (Table 4, en-
tries 4, 6, and 9).
Indoles, t-BuOH, hexane-2,5-diol, and montmorillonite K-10 were
purchased from Aldrich and were used without further purification
or pretreatment. The reactions were carried out at constant temper-
ature in a Discover Benchmate microwave reactor with continuous
stirring. The temperature was measured and controlled by a built-in
infrared detector. The 1H, and 13C NMR spectra were recorded on a
300 MHz Varian NMR spectrometer, in CDCl3. TMS, or the resid-
ual solvent signal was used as internal reference. The MS identifi-
cation of the products have been carried out by an Agilent 6850 GC
& 5973 MS system (70 eV electron impact ionization) using a 30 m
long DB-5 type column (J & W Scientific). The melting points are
uncorrected and were recorded on a MEL-TEMP apparatus.
Scheme 2 shows the proposed mechanism for the synthe-
sis of 1,4-dimethylcarbazole from indole and hexane-2,5-
diol. In the first step, hexane-2,5-diol is protonated by K-
10. This is followed by condensation of the protonated
species to form 2,5-dimethyltetrahydrofuran.17 2,5-Di-
methyltetrahydrofuran is protonated again facilitating nu-
cleophilic attack by C-3 of indole, which upon opening
leads first to alkylation of indole. This is followed by a
second nucleophilic attack by indole to form a cyclic tet-
rahydrocarbazole intermediate.18 We have reported earlier
that, mostly under microwave-assisted conditions, K-10
was able to execute aerobic oxidative dehydrogenation,
including amine oxidation19 or oxidative aromatization.16
This is exactly what we have observed here as well. In the
All products were characterized by mass spectrometry, 1H, and 13
C
NMR spectroscopy. The obtained spectra were in agreement with
the expected structures and in case of known compounds with the
Synthesis 2009, No. 23, 4010–4014 © Thieme Stuttgart · New York

PAPER
Microwave-Assisted Friedel–Crafts Alkylation/Annulation of Indoles
4013
OH
OH2
H
– H2O
– H
O
OH
OH
H
H
HO
OH2
OH
N
N
H
H
N
H
– H2O
– 2 H2
– H
N
H
N
N
H
H
H
Scheme 2 Proposed mechanism for the synthesis of 1,4-dimethylcarbazole from indole and hexane-2,5-diol
literature data. Here, the spectral data and other characterization are
only listed for the previously unknown compounds.
3-tert-Butyl-(1H)-indole-5-carbonitrile (Table 2, Entry 4)
Colorless crystals; mp 117–118 °C.
1H NMR (300.1 MHz, CDCl3): d = 8.31 (br s, 1 H), 8.09 (s, 1 H),
7.33 (m, 2 H), 6.99 (d, J = 2.4 Hz, 1 H), 1.36 (s, 9 H).
13C NMR (75.5 MHz, CDCl3): d = 138.8, 127.6, 126.8, 125.6,
124.2, 121.4, 116.8, 112.1, 101.5, 31.5, 30.6.
MS: m/z (%) = 198 (M+, 19), 183 (100), 168 (7), 155 (16), 143 (10),
127 (4), 116 (4), 101 (2).
Alkylation of Indoles Using tert-Butyl Alcohol; General Proce-
dure
The appropriate indole (1 mmol) and t-BuOH (111 mg, 1.5 mmol)
were dissolved in CH2Cl2 (10 mL). Montmorillonite K-10 (500 mg)
was added and the mixture stirred at r.t. for 2 min. The solvent was
evaporated under vacuum. The dry mixture was then transferred to
a reaction vial and placed into the cavity of the microwave reactor.
The mixture was irradiated at the desired temperature for a preset
time at atmospheric pressure in an open system. The progress of the
reaction was monitored by GC-MS. After the completion of the re-
action, the product was dissolved in CH2Cl2 (3 mL) and the catalyst
removed by filtration. The solvent was evaporated under vacuum.
The crude products were purified by flash chromatography (98:2
hexane–EtOAc) (Table 2).
Methyl 3-tert-Butyl-(1H)-indole-5-carboxylate (Table 2, Entry
5)
Colorless crystals; mp 118–119 °C.
1H NMR (300.1 MHz, CDCl3): d = 8.59 (s, 1 H), 8.22 (br s, 1 H),
7.88 (dd, J = 8.7, 1.5 Hz, 1 H), 7.35 (d, J = 8.8 Hz, 1 H), 6.99 (d,
J = 2.4 Hz, 1 H), 3.94 (s, 3 H), 1.47 (s, 9 H).
13C NMR (75.5 MHz, CDCl3): d = 168.6, 140.2, 128.3, 125.6,
124.3, 123.0, 120.9, 117.1, 111.1, 52.0, 31.7, 31.0.
3-tert-Butyl-5-chloro-(1H)-indole (Table 2, Entry 2)
Colorless oil.
MS: m/z (%) = 231 (M+, 23), 216 (100), 200 (7), 184 (11), 168 (2),
157 (12), 143 (9), 128 (5), 115 (5), 99 (2).
1H NMR (300.1 MHz, CDCl3): d = 7.79 (br s, 1 H), 7.77 (s, 1 H),
7.21 (d, J = 8.4 Hz, 1 H), 7.10 (dd, J = 8.4, 2.1 Hz, 1 H), 6.90 (d,
J = 2.4 Hz, 1 H), 1.41 (s, 9 H).
3-tert-Butyl-5-methoxy-(1H)-indole (Table 2, Entry 6)
Brown oil.
13C NMR (75.5 MHz, CDCl3): d = 135.4, 126.8, 126.5, 124.3,
1H NMR (300.1 MHz, CDCl3): d = 7.77 (br s, 1 H), 7.26 (d, J = 2.1
Hz, 1 H), 7.22 (d, J = 8.7 Hz, 1 H), 6.89 (d, J = 2.4 Hz, 1 H), 6.84
(dd, J = 8.7, 2.4 Hz, 1 H), 3.87 (s, 3 H), 1.43 (s, 9 H).
13C NMR (75.5 MHz, CDCl3): d = 153.1, 132.4, 126.2, 120.2,
111.8, 111.1, 103.8, 102.1, 56.0, 31.4, 30.5.
121.6, 120.6, 120.5, 112.1, 31.4, 30.6.
MS: m/z (%) = 207 (M+, 24), 192 (100), 177 (8), 157 (21), 141 (7),
128 (5), 117 (6), 102 (4).
3-tert-Butyl-5-nitro-(1H)-indole (Table 2, Entry 3)
Yellow crystals; mp 122–123 °C.
MS: m/z (%) = 203 (M+, 23), 188 (100), 173 (11), 157 (6), 145 (10),
130 (6), 115 (7), 104 (4).
1H NMR (300.1 MHz, CDCl3): d = 8.79 (d, J = 1.8 Hz, 1 H), 8.62
(br s, 1 H), 8.09 (dd, J = 9.0, 2.1 Hz, 1 H), 7.41 (d, J = 9 Hz, 1 H),
7.12 (d, J = 2.4 Hz, 1 H), 1.47 (s, 9 H).
3-tert-Butyl-(1H)-indol-5-ol (Table 2, Entry 7)
Brown oil.
13C NMR (75.5 MHz, CDCl3): d = 140.7, 140.3, 129.2, 125.1,
1H NMR (300.1 MHz, CDCl3): d = 7.75 (br s, 1 H), 7.23 (d, J = 2.4
Hz, 1 H), 7.19 (d, J = 8.7 Hz, 1 H), 6.90 (d, J = 2.7 Hz, 1 H), 6.74
(dd, J = 8.7, 2.4 Hz, 1 H), 4.73 (s, 1 H), 1.41 (s, 9 H).
122.5, 118.4, 117.1, 111.2, 31.5, 30.7
MS: m/z (%) = 218 (M+, 22), 203 (100), 187 (8), 170 (4), 157 (41),
142 (9), 128 (11), 115 (10), 102 (4).
Synthesis 2009, No. 23, 4010–4014 © Thieme Stuttgart · New York

4014
A. Kulkarni et al.
PAPER
13C NMR (75.5 MHz, CDCl3): d = 148.4, 132.4, 126.4, 126.0,
M.; Prakash, G. K. S. Catal. Lett. 1996, 42, 5.
120.4, 111.7, 111.1, 105.9, 31.4, 30.5.
(g) Beregszászi, T.; Török, B.; Molnár, Á.; Olah, G. A.;
Prakash, G. K. S. Catal. Lett. 1997, 48, 83. (h) Török, B.;
Kiricsi, I.; Molnár, Á.; Olah, G. A. J. Catal. 2000, 193, 132.
(i) Olah, G. A.; Török, B.; Joschek, J. P.; Bucsi, I.; Estevez,
P. M.; Rasul, G.; Prakash, G. K. S. J. Am. Chem. Soc. 2002,
124, 11379.
MS: m/z (%) = 189 (M+, 29), 174 (100), 159 (8), 145 (6), 133 (7),
118 (2), 104 (3).
3-tert-Butyl-5-methyl-(1H)-indole (Table 2, Entry 8)
Colorless crystals; mp 53–54 °C.
1H NMR (300.1 MHz, CDCl3): d = 7.74 (br s, 1 H), 7.59 (s, 1 H),
7.24 (d, J = 8.1 Hz, 1 H), 6.99 (dd, J = 8.2, 1.2 Hz, 1 H), 6.89 (d,
J = 2.1 Hz, 1 H), 2.47 (s, 3 H), 1.44 (s, 9 H).
13C NMR (75.5 MHz, CDCl3): d = 135.4, 127.8, 126.2, 126.0,
122.9, 120.9, 119.3, 110.9, 31.5, 30.6, 21.7.
MS: m/z (%) = 187 (M+, 24), 172 (100), 157 (10), 144 (7), 130 (7),
117 (5), 102 (3).
(4) (a) Chung, J. Y. L.; Dormer, P. G.; Variankaval, N.; Ball, R.
G.; Tsou, N. N. Org. Lett. 2008, 10, 3037. (b) Sui, Y.; Liu,
L.; Zhao, J.; Wang, D.; Chen, Y. Tetrahedron 2007, 63,
5173. (c) Lu, S.; Du, D.; Xu, J. Org. Lett. 2006, 8, 2115.
(d) Li, D.; Guo, Y.; Ding, Y.; Xiao, W. Chem. Commun.
2006, 799. (e) Jia, Y.; Zhu, S.; Yang, Y.; Zhou, Q. J. Org.
Chem. 2006, 71, 75.
(5) (a) Yadav, J. S.; Subba Reddy, B. V.; Rao, K. V. R.;
Narayan Kumar, G. G. K. S. Tetrahedron Lett. 2007, 48,
5573. (b) Jana, U.; Maiti, S.; Biswas, S. Tetrahedron Lett.
2007, 48, 7160. (c) Whitney, S.; Grigg, R.; Derrick, A.;
Keep, A. Org. Lett. 2007, 9, 3299. (d) Matsuzawa, H.;
Kanao, K.; Miyake, Y.; Nishibayashi, Y. Org. Lett. 2007, 9,
5561.
(6) Dasgupta, S.; Török, B. Curr. Org. Synth. 2008, 5, 321.
(7) (a) Corma, A. Chem. Rev. 1995, 95, 559. (b) Gates, B. C.
Catalysis by Solid Acids, In Encyclopedia of Catalysis, Vol.
2; Horváth, I., Ed.; Wiley: New York, 2003, 104. (c) Yip,
A. C. K.; Lam, F. L. Y.; Hu, X. J. Chem. Commun. 2005,
3218. (d) Varma, R. S. Tetrahedron 2002, 58, 1235.
(8) Yadav, G. D.; Kamble, S. B. Ind. Eng. Chem. Res. 2009, 48,
in press; DOI: 10.1021/ie800737v.
(9) Velu, S.; Swamy, C. S. Res. Chem. Intermed. 2000, 26, 295.
(10) (a) Balogh, M.; Laszlo, P. Organic Chemistry Using Clays;
Springer-Verlag: Berlin, 1993. (b) Kappe, C. O.; Stadler, A.
Microwaves in Organic and Medicinal Chemistry; Wiley-
VCH: Weinheim, 2005. (c) Li, A.; Li, T.; Ding, T. Chem.
Commun. 1997, 1389. (d) Polshettiwar, V.; Varma, R. S.
Acc. Chem. Res. 2008, 41, 629. (e) Dasgupta, S.; Török, B.
Org. Prep. Proced. Int. 2008, 40, 1.
Substituted Carbazoles; General Procedure
The same procedure described above was applied using appropriate
indole (1 mmol) and hexane-2,5-diol (177 mg, 1.5 mmol). The
crude products were purified by flash chromatography (95:5 hex-
ane–EtOAc). The spectra of the isolated products were in agree-
ment with the literature data12 (Table 4).
1,4-Dimethyl-6-nitro-(9H)-carbazole (Table 4, Entry 7)
Yellow crystals; mp 170–172 °C.
1H NMR (300.1 MHz, CDCl3): d = 9.06 (d, J = 2.1 Hz, 1 H), 8.46
(br s, 1 H), 8.36 (dd, J = 8.8, 1.5 Hz, 1 H), 7.50 (d, J = 8.4 Hz, 1 H),
7.24 (d, J = 7.5 Hz, 1 H), 7.05 (d, J = 7.5 Hz, 1 H), 2.89 (s, 3 H),
2.57 (s, 3 H).
13C NMR (75.5 MHz, CDCl3): d = 139.2, 138.1, 131.0, 127.9,
127.1, 125.9, 125.2, 122.5, 121.6, 119.2, 118.1, 110.0, 20.3, 16.7.
MS: m/z (%) = 240 (M+, 100), 225 (10), 210 (24), 194 (45), 178
(12), 167 (14), 152 (12), 115 (7), 96 (10).
References
(11) While a minimal amount of solvent was used during the
sample preparation and product isolation, the reaction itself
occurred under solvent-free conditions. Thus, the complete
process is not solvent-free.
(12) Abid, M.; Spaeth, A.; Török, B. Adv. Synth. Catal. 2006,
348, 2191.
(1) (a) Gribble, G. W. J. Chem. Soc., Perkin Trans. 1 2000,
1045. (b) Nobuyoshi, A.; Akihiko, O.; Chikara, M.; Tatsuya,
T.; Masami, O.; Hiromitsu, S. J. Med. Chem. 1999, 42,
2946. (c) Török, M.; Abid, M.; Mhadgut, S. C.; Török, B.
Biochemistry 2006, 45, 5377.
(13) Knöler, H. J.; Reddy, K. R. Chem. Rev. 2002, 102, 4303.
(14) Iraqi, A.; Wataru, I. Chem. Mater. 2004, 16, 442.
(15) (a) Knölker, H. J. Curr. Org. Synth. 2004, 1, 309. (b) Sanz,
R.; Escribano, J.; Pedrosa, M. R.; Aguado, R.; Arnàiz, F. J.
Adv. Synth. Catal. 2007, 349, 713.
(2) (a) Cacchi, B.; Fabrizi, G. Chem. Rev. 2005, 105, 2873.
(b) Török, B.; Abid, M.; London, G.; Esquibel, J.; Török,
M.; Mhadgut, S. C.; Yan, P.; Prakash, G. K. S. Angew.
Chem. Int. Ed. 2005, 44, 3086. (c) Abid, M.; Teixeira, L.;
Török, B. Org. Lett. 2008, 10, 933.
(16) (a) Kulkarni, A.; Abid, M.; Török, B.; Huang, X.
Tetrahedron Lett. 2009, 50, 1791. (b) De Paolis, O.;
Teixeira, L.; Török, B. Tetrahedron Lett. 2009, 50, 2939.
(17) Török, B.; Bucsi, I.; Beregszászi, T.; Kapocsi, I.; Molnár, Á.
J. Mol. Catal. A: Chem. 1996, 107, 305.
(18) (a) Molnár, Á.; Török, B.; Bucsi, I.; Földvári, A. Top. Catal.
1998, 6, 9. (b) Molnár, Á.; Ledneczki, I.; Bucsi, I.; Bartók,
M. Catal. Lett. 2003, 89, 1. (c) Ledneczki, I.; Forgo, P.;
Molnár, Á. Catal. Lett. 2007, 119, 296.
(3) (a) Heaney, H. In Comprehensive Organic Synthesis, Vol.
2; Trost, B. M.; Fleming, I., Eds.; Pergamon: Oxford, 1991,
733. (b) Heaney, H. In Comprehensive Organic Synthesis,
Vol. 2; Trost, B. M.; Fleming, I., Eds.; Pergamon: Oxford,
1991, 753. (c) Olah, G. A.; Krishnamurti, R.; Prakash, G. K.
S. In Comprehensive Organic Synthesis, Vol. 1; Trost, B.
M.; Fleming, I., Eds.; Pergamon: Oxford, 1991, 293.
(d) Yonezawa, N.; Hino, T.; Ikeda, T. Recent Res. Dev.
Synth. Org. Chem. 1998, 1, 213. (e) Friedel–Crafts and
Related Reactions; Olah, G. A., Ed.; Wiley: New York,
1963–1965. (f) Olah, G. A.; Török, B.; Shamma, T.; Török,
(19) Landge, S.; Atanassova, V.; Thimmaiah, M.; Török, B.
Tetrahedron Lett. 2007, 48, 5161.
Synthesis 2009, No. 23, 4010–4014 © Thieme Stuttgart · New York