Gold-catalyzed sequential alkyne activation: One-pot synthesis of NH-carbazoles via cascade hydroarylation of alkyne/6-endo-dig carbocyclization reactions

Article abstract of DOI:10.1021/jo400799b

A simple and efficient one-pot protocol for the synthesis of NH-carbazoles has been described. The strategy comprises a one-pot reaction involving the treatment of 2-alkynyl indoles with arylacetylenes in the presence of an Au-Ag combination catalyst. The salient feature of the strategy involves sequential activation of terminal and internal alkynes leading to the cascade hydroarylation of terminal alkynes and 6-endo-dig carbocyclization reactions. The generality of the method has been demonstrated by using a series of 2-alkynyl indoles and arylacetylenes.

Full text of DOI:10.1021/jo400799b

Note
pubs.acs.org/joc
Gold-Catalyzed Sequential Alkyne Activation: One-Pot Synthesis of
NH-Carbazoles via Cascade Hydroarylation of Alkyne/6-Endo-Dig
Carbocyclization Reactions
Srinivas Samala,† Anil K. Mandadapu,† Mohammad Saifuddin,† and Bijoy Kundu*,†,‡,§
‡
†Medicinal and Process Chemistry Division and Sophisticated Analytical Instrumental Facility, CSIR-Central Drug Research
Institute, Lucknow 226001, India
§Academy of Scientific and Innovative Research, New Delhi 110001, India
S
* Supporting Information
ABSTRACT: A simple and efficient one-pot protocol for the
synthesis of NH-carbazoles has been described. The strategy
comprises a one-pot reaction involving the treatment of 2-
alkynyl indoles with arylacetylenes in the presence of an Au−
Ag combination catalyst. The salient feature of the strategy
involves sequential activation of terminal and internal alkynes
leading to the cascade hydroarylation of terminal alkynes and
6-endo-dig carbocyclization reactions. The generality of the
method has been demonstrated by using a series of 2-alkynyl
indoles and arylacetylenes.
In recent years, the gold-catalyzed reactions1 involving the
addition of a wide variety of nucleophiles (C/N/O) to a
terminal or internal alkyne in an intramolecular or intermo-
lecular format has offered opportunities for the development of
new methodologies for the synthesis of N-heterocycles in a
one-pot procedure. Nitrogen heterocycles are structural
constituents of many natural products, medicinally important
compounds,2 and organic materials.3 Among them, carbazoles
are an important class of heteroaromatic compounds present in
many bioactive natural products (carbazomycins/mahanim-
bine4), pharmaceuticals,5 and materials,6 and they possess a
broad spectrum of biological activities.7 Therefore, synthesis of
carbazoles has remained a subject of intense investigation in
recent years.8 However, despite being an attractive synthetic
target, a one-pot synthesis of NH-carbazoles from readily
available materials is scarcely available.9 Strategies for the
multistep synthesis reported in the literature suffer from
drawbacks such as low yields and poor generality.10
In a continuation of our efforts on the one-pot synthesis of
diverse heterocycles from 2-alkynyl indoles,11 which acts as a
combined source for both a nucleophile (indole) and an
electrophile (an internal alkyne), we embarked on yet another
application involving the construction of 2,4 -substituted NH-
carbazoles by treating the 2-alkynyl indole with a terminal aryl
alkyne. We envisioned that initially the terminal alkyne may
undergo hydroarylation12 with 2-alkynyl indole via metal-
catalyzed activation to form an enyne intermediate, which may
then undergo intramolecular carbocyclization to afford NH-
carbazoles. For the metal catalyzed activation of the terminal
alkyne, we proposed the use of Au(I) salts, as they have been
widely used to promote cyclization,13 cycloaddition,14 cyclo-
isomerization,15 and rearrangements.16
In our initial experiments, treatment of 2-alkynyl indole 1a
with a terminal alkyne 2a in the presence of 5 mol % of either
AuClPPh3 or AuCl3 as a catalyst was unsuccessful (entries 1
and 2). This prompted us to carry out the desired cyclization by
employing a catalytic combination of Au(I) and Ag(I) salts. In
recent years, gold-catalyzed reactions in the presence of Ag(I)
salts have been demonstrated to promote intramolecular
cyclization involving an alkyne and a nucleophile via an
efficient cationic gold species.1 Accordingly, the 2-alkynyl
indole 1a was treated with the terminal alkyne 2a in DCE at 90
°C in the presence of 5 mol % AuClPPh3/AgSbF6. After
overnight stirring, a new product was isolated in 45% yield with
a molecular weight of 319.1 Da (entry 3, Table 1). The
structure of the product was elucidated by NMR studies that
led to its identification as 2,4-diphenyl-9H-carbazole 3aa.
Once the structure was determined, we then proceeded to
optimize the reaction conditions with a view to enhance the
yield of 3aa, and the results have been summarized in Table 1.
Switching to other solvents such as toluene and acetonitrile
(ACN) in the presence of 5 mol % catalyst loading afforded 3aa
in 55% and 42% isolated yield, respectively (entries 4 and 5).
However, increasing the catalyst loading to 15 mol % in toluene
afforded 3aa in an improved yield of 71% (entry 6). Replacing
Au(I) with Au(III) catalyst furnished 3aa in reduced yields
(entries 7 and 8), thereby suggesting that in comparison to
Au(III), the Au(I) catalyst produced better results. These
Received: April 22, 2013
Revised: June 11, 2013
Accepted: June 17, 2013
© XXXX American Chemical Society
A
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Table 1. Optimization of the Reaction Condition for the Synthesis of 3aa
a
entry
catalyst/solvent
temp (°C)
time (h)
yield (%)
b
1
5 mol % AuClPPh3, DCE
90
90
10
10
10
10
10
10
12
10
24
16
16
24
9.5
9
NR
b
2
5 mol % AuCl3, DCE
NR
3
5 mol % AuClPPh3/AgSbF6, DCE
5 mol % AuClPPh3/AgSbF6, toluene
5 mol % AuClPPh3/AgSbF6, ACN
15 mol % AuClPPh3/AgSbF6, toluene
5 mol % AuCl3/AgOTf, DCE
5 mol % AuCl3/AgOTf, toluene
5 mol % AuCl3/AgSbF6, toluene
5 mol % AuClPPh3/AgOTf, toluene
15 mol % AuClPPh3/AgOTf, toluene
5 mol % AuClPPh3/AgNO3, toluene
10 mol % InCl3, DCE
90
45
55
42
71
35
41
4
110
85
5
6
110
90
7
8
110
110
110
110
110
90
b
9
NR
10
11
12
13
14
15
16
17
45
52
b
NR
41
47
15 mol % InCl3, toluene
90
b
5 mol % PdCl2(PPh3)2, PPh3, toluene
5 mol % Pd2(dba)3, toluene
110
110
110
24
24
24
NR
b
NR
b
5 mol % AgSbF6, toluene
NR
a
b
Isolated yield. NR = no reaction.
Figure 1. Plausible mechanism for the synthesis of 3aa.
findings are in accordance with the observation reported earlier
by Toste et al.17 Further, replacing AuClPPh3 with 5 mol % of
the combination of AuCl3/AgSbF6 failed to afford the desired
product (entry 9, Table 1). We next examined the reaction
conditions by replacing AgSbF6 with other Ag salts. Employing
5 and 15 mol % AgOTf furnished 3aa in 45% and 52% isolated
yields (entries 10 and 11), whereas AgNO3 failed to afford 3aa
(entry 12). Replacing Au(I) catalyst with InCl3 furnished 3aa in
moderate yields (entries 13 and 14), whereas employing Pd
catalysts failed to even promote the formation of 3aa (entries
15 and 16). Controlled experiments without the addition of Au
catalysts failed to furnish 3aa (entry 17). Thus, among the
many reaction conditions screened, 15 mol % AuClPPh3/
AgSbF6 in toluene was found to be the optimal conditions for
the synthesis of NH-carbazoles in one-pot (entry 6, in bold).
A plausible mechanism for the formation of 3aa via the
AuClPPh3/AgSbF6 catalyzed reaction is depicted in Figure 1.
Initially, a cationic Au complex obtained18 from mixing
B
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Note
a
Table 2. Substrate Scope for the Gold Catalyzed One-Pot Synthesis of Carbazoles 3
entry
1
2
time (h)
3
yield (%)
1
1a
1a
1a
1a
1b
1b
1b
1c
1c
1c
1c
1c
1c
1d
1d
1d
1e
1e
1e
1f
2a
2b
2c
2d
2a
2b
2c
2a
2b
2c
2d
2e
2f
8
7.5
8
3aa
3ab
3ac
3ad
3ba
3bb
3bc
3ca
3cb
3cc
3cd
3ce
3cf
71
70
66
72
70
76
71
78
69
74
70
58
52
60
53
50
67
65
68
75
70
68
72
56
2
3
4
7
5
8
6
6.5
7
7
8
8.5
7.5
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
7
15
24
9.5
8.5
9
2a
2b
2c
2a
2b
2d
2a
2c
2a
2a
2e
3da
3db
3dc
3ea
3eb
3ed
3fa
8.5
8
8
6.5
6
1f
3fc
1g
1h
1h
6.5
7
3ga
3ha
3he
16
a
Reaction conditions: 1 equiv of 1, 1.2 equiv of 2, 5 mL of toluene, and 15 mol % of AuClPPh3/AgSbF6
AuClPPh3 and AgSbF6 in a 1:1 ratio activates the terminal
alkyne 2a, which is then followed by its hydroarylation with 1a
to afford a C-3 alkenylated indole intermediate II. The metal
present in II subsequently coordinates with the internal alkyne
present at the C-2 position of the indole to afford intermediate
III. This in turn activates the alkyne toward intramolecular
nucleophilic attack by the alkenyl carbon (at the C-3 position of
the indole) via 6-endo-dig carbocyclization mode to furnish
intermediate IV. Later on, further protodemetalation affords
3aa with the regeneration of catalyst. Having established the
optimized conditions for the synthesis of NH-carbazoles, we
next explored the reaction of a variety of substituted 2-alkynyl
indoles 1a−h and phenylacetylenes 2a−f to examine the scope
and limitations of the cascade hydroarylation−6-endo-dig
carbocyclization reactions. The R3 in 2 (Table 2) represents
substitution on the terminal aryl alkyne comprising electron-
donating and -withdrawing substituents, whereas the R2 in 1
represents substitution on internal alkynes linked to the C-2 of
the indole and comprises both aliphatic and aromatic moieties.
The R1 in 1 represents substitution on the aromatic ring and
comprises either a 5-Cl group or H.
The results demonstrated that a wide range of terminal
alkynes bearing both electron-withdrawing and electron-
donating groups (R3) were found to be suitable substrates for
the cyclization and gave the corresponding products in
moderate to excellent yields. For example, terminal alkynes
bearing t-butyl, methyl, or methoxyl substituents provided the
desired products in good yields (3ab, 3ac, 3ad, and 3cc).
Terminal alkynes containing a halogen atom (F) or electron-
withdrawing substituents (CN) as R3 also underwent the
cyclization smoothly to afford the corresponding product in
moderate yields (3he, 3ce, and 3cf). The moderate yield may
be attributed to the poor π-coordination between the gold
catalyst and alkynes bearing either halogen or electron-
withdrawing groups, thereby leading to the weak activation of
alkynes toward nucleophilic attack. Similarly, in the internal
alkynes 2, the presence of an aromatic ring as R2 furnished
products in good yields, whereas the presence of aliphatic
C
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Note
128.6, 127.8, 127.7, 127.4, 125.9, 122.9, 122.6, 121.0, 120.3, 119.4,
110.6, 108.1. HRMS (MALDI-TOF/TOF): calcd for C24H17N [M+•],
319.1355; found, 319.1352.
substitutents (n-butyl and cyclohexenyl) gave corresponding
products in moderate yields. Introduction of the 5-Cl group,
instead of the 5-H group, in the aromatic ring of the indole had
no effect on the yield of the corresponding 3. Replacing
phenylacetylenes 2 with aliphatic terminal alkynes failed to give
desired products. All 24 NH-carbazoles with diverse sub-
stitutions (R1, R2, and R3) were synthesized in isolated yields
ranging from 50 to 78% (Table 2).
In conclusion, we have developed an efficient gold catalyzed
annulation reaction that allows the assembly of NH-carbazoles
from two readily accessible building blocks, 2-alkynyl indoles
and terminal alkynes, in moderate to good yields. The strategy
involves tandem gold-catalyzed reactions leading to two C−C
bonds forming via sequential hydroarylaion of the alkyne and 6-
endo-dig carbocyclization. The methodology allows direct
synthesis of NH-carbazoles with three-point diversity.
4-(4-(tert-Butyl)phenyl)-2-phenyl-9H-carbazole (3ab). Pale yellow
solid. Rf = 0.42 (10:90 ethyl acetate/hexane). Yield: 70% (0.242 g).
Mp: 203−205 °C. FT-IR (KBr): 3397, 2932, 1600, 1403, 1321, 832
1
cm−1. H NMR (300 MHz, CDCl3): δ 8.16 (s, 1H), 7.72 (d, J = 7.6
Hz, 2H), 7.65−7.55 (m, 6H), 7.49−7.33 (m, 6H), 7.02 (t, J = 6.8 Hz,
1H), 1.46 (s, 9H). 13C NMR (75 MHz, CDCl3): δ 150.8, 141.8, 140.7,
140.3, 139.1, 138.3, 138.1, 129.1, 129.0, 127.7, 127.3, 125.9, 125.5,
123.0, 122.7, 121.2, 120.3, 119.3, 110.6, 107.9, 34.9, 31.7. HRMS
(ESI): calcd for C28H26N [M + H], 376.2065; found, 376.2055.
2-Phenyl-4-(p-tolyl)-9H-carbazole (3ac). White solid. Rf = 0.44
(10:90 ethyl acetate/hexane). Yield: 66% (0.202 g). Mp: 133−135 °C.
1
FT-IR (KBr): 3417, 2922, 1601, 1453, 1411, 1322 cm−1. H NMR
(300 MHz, CDCl3): δ 8.19 (s, 1H), 7.71 (d, J = 7.1 Hz, 2H), 7.60−
7.55 (m, 4H), 7.48−7.36 (m, 8H), 7.00 (t, J = 6.9 Hz, 1H), 2.49 (s,
3H). 13C NMR (75 MHz, CDCl3): δ 141.8, 140.7, 140.4, 139.2, 138.4,
138.1, 137.5, 129.4, 129.3, 129.0, 127.7, 127.3, 125.8, 123.1, 122.7,
121.1, 120.3, 119.4, 110.6, 107.9, 21.5. HRMS (ESI): calcd for
C25H20N [M + H], 334.1596; found, 334.1593.
EXPERIMENTAL SECTION
■
I. General Information and Methods. All reagents and solvents
were purchased from commercial sources and used without
purification. NMR spectra were recorded with 300 and 400 MHz
spectrometers for 1H NMR and 75 and 100 MHz for 13C NMR.
Chemical shifts (δ) are given in parts per million relative to the
residual signals of tetramethylsilane in CDCl3 or deuterated solvent
4-(4-Methoxyphenyl)-2-phenyl-9H-carbazole (3ad). White solid.
Rf = 0.48 (10:90 ethyl acetate/hexane). Yield: 72% (0.231 g). Mp:
121−123 °C. FT-IR (KBr): 3397, 2923, 1606, 1451, 1320, 748 cm−1.
1H NMR (300 MHz, CDCl3): δ 8.17 (s, 1H), 7.69 (d, J = 7.6 Hz, 2H),
7.61−7.55 (m, 4H), 7.44 (t, J = 7.3 Hz, 2H), 7.35 (d, J = 4.6 Hz, 4H),
7.07 (d, J = 8.2 Hz, 2H), 7.00 (t, J = 7.5 Hz, 1H), 3.91 (s, 3H). 13C
NMR (75 MHz, CDCl3): δ 159.4, 141.8, 140.7, 140.4, 139.2, 137.8,
133.8, 130.8, 130.5, 129.0, 127.7, 127.3, 125.8, 123.1, 122.6, 121.1,
120.4, 119.4, 114.1, 113.9, 110.6, 107.9, 55.6. HRMS (MALDI-TOF/
TOF): calcd for C25H19NO [M+•], 349.1461; found, 349.1474.
4-Phenyl-2-(p-tolyl)-9H-carbazole (3ba). White solid. Rf = 0.46
(10:90 ethyl acetate/hexane). Yield: 70% (0.214 g). Mp: 131−133 °C.
1
CDCl3 for H and 13C NMR. Multiplicities are reported as follows:
singlet (s), doublet (d), doublet of doublets (dd), doublet of triplets
(dt), triplet (t), quartet (q), multiplet (m). High resolution mass
spectra were taken with a 3000 mass spectrometer and MALDI-TOF/
TOF Analyzer. Column chromatography was performed using silica
gel (100−200 mesh) as the stationary phase. All reactions were
monitored by thin layer chromatography (TLC). The purity and
characterization of these compounds were further established using
HR/EI mass spectroscopy. Melting points were measured on a
capillary melting point apparatus and are uncorrected.
II. Synthesis of 2-Ethynyl-1H-indoles 1a−h. Starting materials
1a−h were prepared according to the literature procedure.19 The
characterization data of compounds 1a−f and 1h were reported
previously by us.11
1
FT-IR (KBr): 3434, 2923, 1606, 1454, 1320 cm−1. H NMR (300
MHz, CDCl3): δ 8.21 (s, 1H), 7.71 (d, J = 6.6 Hz, 2H), 7.65 (d, J = 8.5
Hz, 3H), 7.59−7.51, (m, 5H), 7.44−7.34 (m, 3H), 7.29 (d, J = 9.7 Hz,
1H), 7.02 (t, J = 7.0 Hz, 1H), 2.44 (s, 3H). 13C NMR (75 MHz,
CDCl3): δ 141.5, 140.7, 140.4, 139.2, 138.8, 138.1, 137.2, 129.7, 129.4,
128.6, 127.8, 127.5, 125.8, 123.0, 122.5, 120.9, 120.1, 119.4, 114.3,
110.6, 107.9, 21.3. HRMS (ESI): calcd for C25H20N [M + H],
334.1596; found, 334.1591.
2-((4-(tert-Butyl)phenyl)ethynyl)-5-chloro-1H-indole (1g). Yellow
solid. Rf = 0.58 (10:90 ethyl acetate/hexane). Yield: 67% (0.661 g).
Mp: 158−160 °C. FT-IR (KBr): 3028, 2964, 1648, 1534, 1458 cm−1.
1H NMR (300 MHz, CDCl3): δ 8.10 (s, 1H), 7.46−7.35 (m, 5H),
4-(4-(tert-Butyl)phenyl)-2-(p-tolyl)-9H-carbazole (3bb). White
solid. Rf = 0.46 (10:90 ethyl acetate/hexane). Yield: 76% (0.272 g).
Mp: 198−200 °C. FT-IR (KBr): 3400, 2955, 1606, 1457, 1325, 1115
1
cm−1. H NMR (300 MHz, CDCl3): δ 8.17 (s, 1H), 7.63−7.53 (m,
6.94 (s, 1H), 6.77 (s, 1H), 6.68 (d, J = 0.9 Hz, 1H), 1.32 (s, 9H). 13
C
8H), 7.42−7.31 (m, 3H), 7.27−7.25 (m, 2H), 7.00 (t, J = 7.1 Hz, 1H),
2.40 (s, 3H), 1.44 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 150.8,
140.8, 140.4, 139.2, 138.9, 138.4, 138.1, 137.1, 129.7, 129.1, 127.5,
125.8, 125.5, 123.2, 122.7, 121.1, 120.2, 119.3, 110.5, 107.7, 34.9, 31.7,
21.3. HRMS (ESI): calcd for C29H28N [M + H], 390.2222; found,
390.2220.
NMR (75 MHz, CDCl3): δ 151.8, 146.4, 143.8, 131.4, 131.2, 125.6,
121.9, 119.9, 117.7, 108.9, 100.9, 92.5, 81.4, 34.9, 31.3. HRMS (ESI):
calcd for C20H19ClN [M + H], 308.1206; found, 308.1214.
III. Typical Procedure for the Synthesis of NH-Carbazoles. A
50 mL round-bottom flask equipped with a magnetic stir bar was
charged with the 2-alkynyl indole 1a−h (1.0 equiv), phenylacetylenes
2a−f (1.2 equiv), and 10 mL of freshly dried toluene. The resulting
solution was purged with N2 for 10 min followed by the addition of
Au(PPh3)Cl (0.15 mmol) and AgSbF6 (0.15 mmol) under the N2
atmosphere. The reaction mixture was transferred to an oil bath and
continued to stir at 110 °C. After being allowed to stir vigorously for
the appropriate time, the reaction mixture was removed from the oil
bath and cooled to room temperature and filtered through a bed of
Celite-R, diluted with water (50 mL), and extracted with ethyl acetate
(3 × 30 mL). The resulting organic solution was washed with brine
(25 mL), dried over anhydrous Na2SO4, filtered, and concentrated in
vacuo. The resulting residue was purified by silica gel flash column
chromatography using EtOAc/hexane as the eluent to afford 3.
Characterization Data of All Final Compounds (3aa−3he). 2,4-
Diphenyl-9H-carbazole (3aa). Gray solid. Rf = 0.48 (10:90 ethyl
acetate/hexane). Yield: 71% (0.208 g). Mp: 170−172 °C. FT-IR
(KBr): 3399, 2927, 1613, 1324, 755 cm−1. 1H NMR (300 MHz,
CDCl3): δ 8.20 (s, 1H), 7.74−7.68 (m, 4H), 7.63 (s, 1H), 7.55−7.44
(m, 6H), 7.41−7.36 (m, 4H), 7.00 (t, J = 7.8 Hz, 1H). 13C NMR (75
MHz, CDCl3): δ 141.7, 141.3, 140.7, 140.3, 139.2, 138.1, 129.4, 129.0,
2,4-di-p-Tolyl-9H-carbazole (3bc). White solid. Rf = 0.42 (10:90
ethyl acetate/hexane). Yield: 71% (0.227 g). Mp: 140−142 °C. FT-IR
1
(KBr): 3392, 2942, 1604, 1455, 1273 cm−1. H NMR (300 MHz,
CDCl3): δ 8.11 (s, 1H), 7.61−7.53 (m, 6H), 7.35−7.32 (m, 5H), 7.25
(d, J = 8.9 Hz, 2H), 7.01−6.96 (m, 1H), 2.48 (s, 3H), 2.40 (s, 3H).
13C NMR (75 MHz, CDCl3): δ 140.7, 140.3, 139.1, 138.9, 138.4,
137.4, 137.1, 129.7, 129.4, 129.3, 127.5, 125.7, 123.1, 122.6, 120.9,
120.1, 119.3, 110.6, 107.7, 21.6, 21.3. HRMS (ESI): calcd for C26H22N
[M + H], 348.1752; found, 348.1741.
2-(4-(tert-Butyl)phenyl)-4-phenyl-9H-carbazole (3ca). White
solid. Rf = 0.51 (10:90 ethyl acetate/hexane). Yield: 78% (0.269 g).
Mp: 178−180 °C. FT-IR (KBr): 3404, 2928, 1606, 1456, 1396, 1322
1
cm−1. H NMR (300 MHz, CDCl3): δ 8.18 (s, 1H), 7.69−7.64 (m,
4H), 7.61 (d, J = 1.3 Hz, 1H), 7.56−7.47 (m, 6H), 7.42−7.33 (m,
3H), 6.98 (t, J = 6.9 Hz, 1H), 1.37 (s, 9H). 13C NMR (75 MHz,
CDCl3): δ 150.4, 141.5, 140.7, 140.3, 139.1, 138.8, 138.0, 129.4, 128.6,
127.8, 127.3, 126.0, 125.8, 123.0, 122.5, 121.0, 120.1, 119.3, 110.6,
107.9, 34.7, 31.6. HRMS (MALDI-TOF/TOF): calcd for C28H25N
[M+•], 375.1981; found, 375.1987.
D
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The Journal of Organic Chemistry
Note
2,4-bis(4-(tert-Butyl)phenyl)-9H-carbazole (3cb). White solid. Rf =
0.50 (10:90 ethyl acetate/hexane). Yield: 69% (0.274 g). Mp: 198−
128.9, 125.3, 125.2, 123.3, 122.5, 122.3, 119.0, 118.9, 110.3, 109.0,
36.2, 34.8, 34.1, 31.6, 22.6, 14.1. HRMS (ESI): calcd for C26H30N [M
+ H], 356.2378; found, 356.2348.
1
200 °C. FT-IR (KBr): 3393, 2942, 1606, 1458, 1382, 1270 cm−1. H
NMR (300 MHz, CDCl3): δ 8.17 (s, 1H), 7.66 (s, 1H), 7.64 (s, 2H),
7.60 (d, J = 4.7 Hz, 2H), 7.56 (s, 2H), 7.53 (s, 1H), 7.47 (d, J = 8.3
Hz, 2H), 7.41−7.36 (m, 3H), 7.00 (t, J = 6.9 Hz, 1H), 1.44 (s, 9H),
1.37 (s, 9H). 13C NMR (75 MHz, CDCl3): δ 150.7, 150.5, 140.8,
140.3, 139.0, 138.9, 138.4, 138.0, 129.0, 127.3, 125.9, 125.7, 125.5,
123.1, 122.6, 121.1, 120.1, 119.3, 110.5, 107.7, 34.9, 34.7, 31.7, 31.6.
HRMS (MALDI-TOF/TOF): calcd for C32H33N [M+•], 431.2613;
found, 431.2603.
2-(4-(tert-Butyl)phenyl)-4-(p-tolyl)-9H-carbazole (3cc). Pale yel-
low solid. Rf = 0.46 (10:90 ethyl acetate/hexane). Yield: 74% (0.265
g). Mp: 174−176 °C. FT-IR (KBr): 3391, 2920, 1606, 1450, 1278,
1140 cm−1. 1H NMR (300 MHz, CDCl3): δ 8.17 (s, 1H), 7.65 (d, J =
8.3 Hz, 2H), 7.59−7.54 (m, 4H), 7.48 (d, J = 8.3 Hz, 2H), 7.39−7.33
(m, 5H), 6.99 (t, J = 7.1 Hz, 1H), 2.49 (s, 3H), 1.37 (s, 9H). 13C NMR
(100 MHz, CDCl3): δ 150.3, 140.6, 140.2, 139.0, 138.8, 138.4, 137.9,
137.3, 129.3, 129.2, 127.2, 125.8, 125.6, 123.0, 122.5, 120.9, 120.0,
119.2, 110.5, 107.7, 34.7, 31.5, 21.5. HRMS (ESI): calcd for C29H28N
[M + H], 390.2222; found, 390.2223.
2-Butyl-4-(p-tolyl)-9H-carbazole (3dc). Black liquid. Rf = 0.54
(10:90 ethyl acetate/hexane). Yield: 50% (0.144 g). FT-IR (neat):
3394, 2923, 1602, 1466, 1246, 1175 cm−1. 1H NMR (300 MHz,
CDCl3): δ 7.99 (s, 1H), 7.53−7.50 (m, 3H), 7.30−7.19 (m, 4H), 7.05
(s, 1H), 6.96−6.92 (m, 2H), 2.73 (t, J = 7.6 Hz, 2H), 2.45 (s, 3H),
1.72−1.64 (m, 2H), 1.42−1.35 (m, 2H), 0.93 (t, J = 7.2 Hz, 3H). 13C
NMR (75 MHz, CDCl3): δ 141.2, 140.5, 140.0, 138.7, 137.5, 137.2,
129.4, 129.2, 128.6, 125.2, 123.3, 122.3, 119.0, 118.9, 110.5, 109.1,
36.2, 34.2, 22.7, 21.5, 14.2. HRMS (ESI): calcd for C23H24N [M + H],
314.1909; found, 314.1896.
2-(Cyclohex-1-en-1-yl)-4-phenyl-9H-carbazole (3ea). Pale yellow
solid. Rf = 0.5 (10:90 ethyl acetate/hexane). Yield: 67% (0.199 g). Mp:
134−136 °C. FT-IR (KBr): 3398, 2925, 1602, 1461, 1246, 1172 cm−1.
1H NMR (300 MHz, CDCl3): δ 8.09 (s, 1H), 7.63 (d, J = 7.2 Hz, 2H),
7.53−7.44 (m, 4H), 7.40 (s, 1H), 7.36 (s, 1H), 7.30 (t, J = 7.0 Hz,
1H), 7.18 (s, 1H), 6.95 (t, J = 7.1 Hz, 1H), 6.26 (s, 1H), 2.53 (s, 2H),
2.24 (d, J = 3.0 Hz, 2H), 1.84−1.80 (m, 2H), 1.69 (d, J = 5.1 Hz, 2H).
13C NMR (75 MHz, CDCl3): δ 141.7, 140.9, 140.5, 140.3, 137.4,
2-(4-(tert-Butyl)phenyl)-4-(4-methoxyphenyl)-9H-carbazole
(3cd). Pale yellow solid. Rf = 0.52 (10:90 ethyl acetate/hexane). Yield:
70% (0.261 g). Mp: 182−184 °C. FT-IR (KBr): 3394, 2923, 1602,
137.0, 129.4, 128.6, 127.6, 125.5, 125.4, 123.2, 122.3, 119.2, 119.1,
110.5, 106.0, 34.0, 32.1, 22.5, 14.3. HRMS (MALDI-TOF/TOF):
calcd for C24H21N [M+•], 323.1668; found, 323.1666.
1
1455, 1320. H NMR (300 MHz, CDCl3): δ 8.17 (s, 1H), 7.66 (s,
4-(4-(tert-Butyl)phenyl)-2-(cyclohex-1-en-1-yl)-9H-carbazole
(3eb). Pale yellow solid. Rf = 0.44 (10:90 ethyl acetate/hexane). Yield:
65% (0.227 g). Mp: 161−163 °C. FT-IR (KBr): 3395, 2928, 1602,
1466, 1246, 1155 cm−1. 1H NMR (300 MHz, CDCl3): δ 8.07 (s, 1H),
7.59−7.51 (m, 5H), 7.37−7.30 (m, 3H), 7.19 (s, 1H), 6.97 (t, J = 7.5
Hz, 1H), 6.25 (s, 1H), 2.52 (s, 2H), 2.24 (s, 2H), 1.80 (d, J = 5.1 Hz,
2H), 1.69 (d, J = 5.4 Hz, 2H), 1.43 (s, 9H). 13C NMR (75 MHz,
CDCl3): δ 150.6, 140.9, 140.5, 140.3, 138.7, 137.4, 137.1, 129.0, 128.5,
125.7, 125.4, 125.3, 123.3, 122.5, 119.8, 119.2, 119.1, 114.3, 110.5,
105.8, 34.9. 31.7, 28.0, 26.2, 23.4, 22.5. HRMS (MALDI-TOF/TOF):
calcd for C28H29N [M+•], 379.2294; found, 379.2292.
1H), 7.63 (s, 1H), 7.61 (s, 1H), 7.58 (d, J = 3.3 Hz, 2H), 7.54 (s, 1H),
7.48 (d, J = 8.3 Hz, 2H), 7.41−7.34 (m, 3H), 7.07 (d, J = 8.6 Hz, 2H),
7.00 (t, J = 6.9 Hz, 1H), 3.92 (s, 3H), 1.37 (s, 9H). 13C NMR (75
MHz, CDCl3): δ 159.4, 150.4, 140.8, 140.4, 139.1, 138.9, 137.7, 133.9,
130.5, 127.3, 125.9, 125.7, 123.2, 122.5, 121.0, 120.3, 119.3, 114.1,
110.6, 107.7, 55.6, 34.7, 31.6. HRMS (ESI): calcd for C29H28NO [M +
H], 406.2171; found, 406.2146.
2-(4-(tert-Butyl)phenyl)-4-(4-fluorophenyl)-9H-carbazole (3ce).
Gray solid. Rf = 0.54 (10:90 ethyl acetate/hexane). Yield: 58%
(0.210 g). Mp: 176−178 °C. FT-IR (KBr): 3345, 2920, 1608, 1450,
1
1278 cm−1. H NMR (400 MHz, CDCl3): δ 8.11 (s, 1H), 7.58−7.53
2-(Cyclohex-1-en-1-yl)-4-(4-methoxyphenyl)-9H-carbazole (3ed).
Pale yellow solid. Rf = 0.52 (10:90 ethyl acetate/hexane). Yield: 68%
(0.221 g). Mp: 143−145 °C. FT-IR (KBr): 3391, 2925, 1603, 1461,
(m, 5H), 7.42−7.37 (m, 3H), 7.33 (d, J = 7.7 Hz, 1H), 7.29−7.25 (m,
1H), 7.17−7.13 (m, 3H), 6.93 (t, J = 7.2 Hz, 1H), 1.30 (s, 9H). 13C
NMR (75 MHz, CDCl3): δ 150.5, 140.7, 140.4, 139.2, 138.7, 137.4,
136.9, 131.1, 131.0, 127.3, 126.0, 125.9, 122.9, 122.3, 121.0, 120.1,
119.5, 115.7, 115.4, 110.7, 108.1, 34.8, 31.6. HRMS (MALDI-TOF/
TOF): calcd for C28H24FN [M+•], 393.1887; found, 393.1868.
4-(2-(4-(tert-Butyl)phenyl)-9H-carbazol-4-yl)benzonitrile (3cf).
Gray solid. Rf = 0.58 (10:90 ethyl acetate/hexane). Yield: 52%
(0.191 g). Mp: 172−174 °C. FT-IR (KBr): 3391, 2920, 2240, 1600,
1450, 1290 cm−1. 1H NMR (400 MHz, CDCl3): δ 8.36 (s, 1H), 7.85−
7.79 (m, 3H), 7.67−7.63 (m, 3H), 7.50 (d, J = 8.2 Hz, 2H), 7.45−7.38
(m, 4H), 7.31 (s, 1H), 7.02 (t, J = 7.4 Hz, 1H), 1.38 (s, 9H). 13C NMR
(75 MHz, CDCl3): δ 150.7, 146.4, 140.8, 140.4, 139.2, 138.4, 135.7,
132.7, 132.5, 130.3, 128.9, 127.3, 126.2, 126.0, 122.3, 122.0, 120.7,
119.6, 119.5, 119.2, 111.5, 111.0, 109.0, 34.8, 31.6. HRMS (MALDI-
TOF/TOF): calcd for C29H24N2 [M+•], 400.1934; found, 400.1927.
2-Butyl-4-phenyl-9H-carbazole (3da). Black liquid. Rf = 0.42
(10:90 ethyl acetate/hexane). Yield: 60% (0.165 g). FT-IR (neat):
3385, 2927, 1600, 1461, 1251, 1172 cm−1. 1H NMR (300 MHz,
CDCl3): δ 8.06 (s, 1H), 7.63 (d, J = 7.2 Hz, 2H), 7.53−7.44 (m, 4H),
7.36 (d, J = 7.9 Hz, 1H), 7.32−7.27 (m, 1H), 7.20 (s, 1H), 6.94 (t, J =
6.8 Hz, 2H), 2.78 (t, J = 7.5 Hz, 2H), 1.75−1.65 (m, 2H), 1.27 (d, J =
10.3 Hz, 2H), 0.94 (t, J = 7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ
141.7, 141.3, 140.6, 140.1, 137.6, 129.5, 128.6, 127.7, 125.4, 124.3,
123.8, 123.3, 122.4, 122.3, 119.2, 119.0, 110.6, 109.4, 36.4, 34.3, 22.8,
14.3. HRMS (MALDI-TOF/TOF): calcd for C22H21N [M+•],
299.1668; found, 299.1666.
1
1245, 1172 cm−1. H NMR (300 MHz, CDCl3): δ 8.07 (s, 1H), 7.56
(d, J = 7.9 Hz, 2H), 7.50 (d, J = 7.8 Hz, 1H), 7.37 (d, J = 4.9 Hz, 2H),
7.31 (t, J = 7.4 Hz, 1H), 7.16 (s, 1H), 7.05 (t, J = 7.9 Hz, 2H), 6.97 (t,
J = 7.6 Hz, 1H), 6.26 (s, 1H), 3.92 (s, 3H), 2.53 (s, 2H), 2.24 (s, 2H),
1.82 (d, J = 4.9 Hz, 2H), 1.70 (d, J = 5.2 Hz, 2H). 13C NMR (75 MHz,
CDCl3): δ 159.3, 140.9, 140.5, 140.3, 137.1, 137.0, 134.1, 130.5, 125.4,
125.3, 123.3, 122.3, 119.9, 119.2, 119.1, 114.0, 110.5, 105.7, 55.6, 28.0,
26.2, 23.4, 22.5. HRMS (ESI): calcd for C25H24NO [M + H],
354.1858; found, 354.1832.
6-Chloro-2,4-diphenyl-9H-carbazole (3fa). Pale yellow solid. Rf =
0.5 (10:90 ethyl acetate/hexane). Yield: 75% (0.210 g). Mp: 181−183
°C. FT-IR (KBr): 3381, 2935, 1605, 1390, 1278, 1150 cm−1. 1H NMR
(300 MHz, CDCl3): δ 8.25 (s, 1H), 7.71 (d, J = 7.6 Hz, 2H), 7.65 (d, J
= 7.0 Hz, 2H), 7.61 (s, 1H), 7.55 (d, J = 7.6 Hz, 3H), 7.49−7.45 (m,
3H), 7.38 (s, 2H), 7.32 (d, J = 2.8 Hz, 2H). 13C NMR (75 MHz,
CDCl3): δ 141.5, 141.2, 140.7, 139.9, 138.6, 138.3, 129.2, 129.0, 128.8,
128.2, 127.7, 127.6, 126.0, 124.7, 124.1, 122.1, 121.4, 119.5, 111.5,
108.3. HRMS (ESI): calcd for C24H17ClN [M + H], 354.1050; found,
354.1041.
6-Chloro-2-phenyl-4-(p-tolyl)-9H-carbazole (3fc). Pale brown
solid. Rf = 0.56 (10:90 ethyl acetate/hexane). Yield: 70% (0.204 g).
Mp: 178−180 °C. FT-IR (KBr): 3395, 2920, 1607, 1400, 1251, 1145
1
cm−1. H NMR (300 MHz, CDCl3): δ 8.21 (s, 1H), 7.69 (d, J = 7.2
Hz, 2H), 7.57−7.53 (m, 4H), 7.45 (t, J = 7.1 Hz, 2H), 7.37−7.34 (m,
4H), 7.30 (s, 2H), 2.50 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 141.6,
141.3, 139.9, 138.6, 138.4, 137.9, 137.8, 129.5, 129.1, 129.0, 127.7,
127.5, 125.9, 124.7, 124.3, 122.2, 121.5, 119.5, 111.5, 108.1, 21.6.
HRMS (MALDI-TOF/TOF): calcd for C25H18ClN [M+•], 367.1122;
found, 367.1125.
2-(4-(tert-Butyl)phenyl)-6-chloro-4-phenyl-9H-carbazole (3ga).
Gray solid. Rf = 0.52 (10:90 ethyl acetate/hexane). Yield: 68%
(0.221 g). Mp: 152−154 °C. FT-IR (KBr): 3386, 2925, 1607, 1461,
2-Butyl-4-(4-(tert-butyl)phenyl)-9H-carbazole (3db). Black liquid.
Rf = 0.46 (10:90 ethyl acetate/hexane). Yield: 53% (0.173 g). FT-IR
(neat): 3382, 2925, 1606, 1456, 1212, 841 cm−1. 1H NMR (300 MHz,
CDCl3): δ 8.02 (s, 1H), 7.59−7.50 (m, 5H), 7.37−7.27 (m, 2H), 7.18
(s, 1H), 6.99−6.95 (m, 2H), 2.77 (t, J = 7.6 Hz, 2H), 1.75−1.65 (m,
2H), 1.43 (s, 9H), 1.41−1.37 (m, 2H), 0.94 (t, J = 7.2 Hz, 3H). 13C
NMR (75 MHz, CDCl3): δ 150.4, 141.1, 140.5, 139.9, 138.5, 137.5,
E
dx.doi.org/10.1021/jo400799b | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
1252, 1165 cm−1. 1H NMR (300 MHz, CDCl3): δ 8.18 (s, 1H), 7.62−
7.54 (m, 5H), 7.42−7.28 (m, 5H), 7.07 (d, J = 7.9 Hz, 2H), 7.02−6.91
(m, 2H), 1.26 (s, 9H). 13C NMR (75 MHz, CDCl3): δ 150.4, 141.0,
140.6, 139.6, 138.4, 138.0, 130.3, 129.5, 129.0, 128.6, 127.9, 127.3,
127.1, 125.8, 125.7, 124.5, 124.0, 121.9, 121.1, 119.1, 113.8, 111.3,
107.8, 34.6, 31.3. HRMS (MALDI-TOF/TOF): calcd for C28H24ClN
[M+•], 409.1591; found, 409.1606.
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6-Chloro-4-phenyl-2-(p-tolyl)-9H-carbazole (3ha). Gray solid. Rf =
0.48 (10:90 ethyl acetate/hexane). Yield: 72% (0.210 g). Mp: 182−
1
184 °C. FT-IR (KBr): 3395, 2925, 1600, 1464, 1246, 1172 cm−1. H
(7) Knolker, H. J.; Reddy, K. R. Chem. Rev. 2002, 102, 4303−4428.
NMR (300 MHz, CDCl3): δ 8.16 (s, 1H), 7.64−7.52 (m, 10H), 7.43
(s, 1H), 7.35 (s, 1H), 7.25 (d, J = 7.7 Hz, 2H), 2.40 (s, 3H). 13C NMR
(75 MHz, CDCl3): δ 141.3, 140.8, 139.9, 138.7, 138.6, 138.3, 137.4,
129.8, 129.2, 128.8, 128.1, 127.5, 125.9, 124.7, 124.2, 122.1, 121.2,
119.3, 111.5, 108.0, 21.3. HRMS (MALDI-TOF/TOF): calcd for
C25H18ClN [M+•], 367.1122; found, 367.1123.
6-Chloro-4-(4-fluorophenyl)-2-(p-tolyl)-9H-carbazole (3he). Gray
solid. Rf = 0.54 (10:90 ethyl acetate/hexane). Yield: 56% (0.171 g).
Mp: 178−180 °C. FT-IR (KBr): 3392, 2920, 1607, 1455, 1195 cm−1.
1H NMR (400 MHz, CDCl3): δ 8.23 (s, 1H), 7.59 (d, J = 8.3 Hz, 5H),
7.41 (s, 1H), 7.31 (s, 3H), 7.28−7.24 (m, 4H), 2.41 (s, 3H). 13C NMR
(75 MHz, CDCl3): δ 141.3, 139.9, 138.6, 138.5, 137.5, 137.1, 136.8,
130.9, 130.8, 129.8, 127.5, 126.0, 124.8, 124.0, 121.8, 121.3, 119.2,
115.9, 115.6, 111.6, 108.2, 21.3. HRMS (MALDI-TOF/TOF): calcd
for C25H17ClFN [M+•], 385.1028; found, 385.1043.
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ASSOCIATED CONTENT
■
S
* Supporting Information
1
Copies of H and 13C NMR spectra of all final compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: b_kundu@cdri.res.in, bijoy_kundu@yahoo.com.
Phone: +91 522 2612411-18. Fax: +91 522 2623405.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
S.S., A.K.M., and M.S. are thankful to CSIR, New Delhi, India,
for financial support. The authors also thank SAIF, CDRI, India
for providing analytical data.
REFERENCES
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dx.doi.org/10.1021/jo400799b | J. Org. Chem. XXXX, XXX, XXX−XXX