Acid-catalyzed condensation of 2,2′-diamino-1,1′-biaryls for the synthesis of benzo[c]carbazoles

Article abstract of DOI:10.1016/j.tetlet.2011.09.001

2,2′-Diamino-1,1′-biaryls were found to undergo ring-closure condensation reaction to afford benzo[c]carbazoles in good to excellent yield. Coupled with the synthesis of 2,2′-biaryldiamines from diaryl hydrazides via [3,3]-sigmatropic rearrangement, it constitutes a new efficient synthetic method for benzo[c]carbazoles and related compounds.

Full text of DOI:10.1016/j.tetlet.2011.09.001

Tetrahedron Letters 52 (2011) 6015–6017
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Acid-catalyzed condensation of 2,20-diamino-1,10-biaryls for the synthesis
of benzo[c]carbazoles
⇑
Byong-Yun Lim, Min-Kyung Choi, Cheon-Gyu Cho
Department of Chemistry and Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
2,20-Diamino-1,10-biaryls were found to undergo ring-closure condensation reaction to afford
benzo[c]carbazoles in good to excellent yield. Coupled with the synthesis of 2,20-biaryldiamines from dia-
ryl hydrazides via [3,3]-sigmatropic rearrangement, it constitutes a new efficient synthetic method for
benzo[c]carbazoles and related compounds.
Article history:
Received 28 July 2011
Revised 26 August 2011
Accepted 1 September 2011
Available online 5 September 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
2,20-Diamino-1,10-biaryls
Benzo[c]carbazole
Dibenzo[c,g]carbazole
[3,3]-Sigmatropic rearrangement
Tandem reaction
Benzo[c]carbazole, albeit rare in nature, is an important struc-
tural motif in medicinal and materials chemistry.1 Efforts have
thus been devoted toward developing general and efficient syn-
thetic methods. However, reported methods suffer from many
drawbacks including low functional group tolerance and selectiv-
ity, imposing limitations on the type and patterns of substituents,
as they require harsh reaction conditions, multiple steps, cumber-
some synthesis of reagents and/or substrates, or a photochemical
reaction setup.2 In connection to our interest on aryl hydrazide,3
we found that 1a and 2a can undergo acid-catalyzed [3,3]-
sigmatropic rearrangement to afford the corresponding diamines
(3a and 4a), along with small amount of carbazole byproducts
(5a and 6a),3a,3h similar to diaryl hydrazines 1a-H and 2a-H
(Scheme 1).4
Not knowing the intensive mechanistic studies conducted on
the similar reaction system in the literature (vide infra),4,5 we have
pondered over the condensation of 3a to 5a as possibly the most
direct synthetic approach to the benzo[c]carbazole (as well as to
dibenzo[c,g]carbazole 6a from 4a). However, a quick literature
survey told us otherwise. In the studies on the mechanism of the
acid-catalyzed rearrangement of 2,20-hydrazonaphthalene 2a-H,
Shine and coworkers reported that diamine 4a cannot cyclize into
carbazole 6a, based on the observation that the ratio of 2,20-
diamino-1,10-binaphthyl 4a to dibenzocarbazole 6a was consistent
and not affected by the extent of the reaction.5 In accordance with
the above, they concluded that the carbazole byproduct 6a was not
produced from 4a, but rather from 7 by following the path B as
suggested by earlier studies (Scheme 2).6 In essence, diamine 4a,
once formed, cannot go back to the imino form 7, at least under
the rearrangement conditions they used. This conceptual irrevers-
ibility of the path A was further corroborated by the work of
ˇ
´
Kocovsky and coworkers on the Cu(II)-mediated oxidative coupling
of 2-amino-naphthalene en route to 2,20-diamino-1,10-biaryls.7
Hence, no examples of attempts for the conversion of either 3 or
4 into the corresponding carbazoles exist in the literature.8 There-
fore, we decided to double check the credibility of the irreversibil-
ity of diamine 4a to imine 7 and eventually carbazole 6a. To this
end, 1-(o-aminophenyl)-2-naphthylamine 3a was subjected first
to the conditions that we used for the [3,3]-sigmatropic rearrange-
ment of diaryl hydrazide.3a,3h When heated in EtOH in the presence
of HCl (aq), 3a gave no noticeable change even after a day. How-
ever, a prolonged heating afforded the desired benzo[c]carbazole
H+
NH2
NH2
NZ
NH
NH
+
1: phenyl
3a: phenyl
4a: naphthyl
5a: phenyl
6a: naphthyl
1a: Z = Boc, 1a-H: Z = H
2: naphthyl
2a: Z = Boc, 2a-H: Z = H
⇑
Corresponding author.
E-mail address: ccho@hanyang.ac.kr (C.-G. Cho).
Scheme 1. Acid-catalyzed rearrangement reactions of diaryl hydrazide and diaryl
hydrazine.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.09.001

6016
B.-Y. Lim et al. / Tetrahedron Letters 52 (2011) 6015–6017
Table 2
Acid-catalyzed condensation of 3b-3i10
A
[H+]
NH2
NH2
NH
NH
NH
NH
H
X
R
R
0.4 M HCl (aq)
in 1,4-dioxane
NH2
NH2
NH
reflux
2a-H
7
4a
3
5
B
Entry
3
Time
5 (Yield)
1
2
3
4
5
6
7
8
3b: R = 5-Me
5
7
7
7
7
7
12
12
5b (93%)
5c (89%)
5d (91%)
5e (90%)
5f (94%)
5g (92%)
5h (trace)a
5i (trace)a
3c: R = 5-OMe
3d: R = 3-OMe
3e: R = 5-t-Bu
3f: R = 5-Ph
3g: R = 5-hexyl
3h: R = 5-CO2Me
3i: R = 5-COMe
NH2
- NH3
NH
H
NH
8
6a
a
SEM remained intact even after 12 days.
Scheme 2. Acid-catalyzed rearrangement of 2a-H: mechanistic pathway.
Table 3
Tandem rearrangement/condensation reactions11
5a (93% yield after 5 days, entry 1, Table 1). The reaction rate
increased in proportion to the reaction temperature, but not so
much to the amount of acid. The reaction was further optimized
by changing the solvent and the reaction temperature. Running
the reaction in acidic 1,4-dioxane (0.4 M HCl(aq)) under reflux con-
dition turned out to be the best, providing 5a in 93% yield after 8 h
(entry 9).
R
0.4 M HCl (aq)
in 1,4-dioxane
R
NBoc
NH
NH
reflux
1
5
The results shown in Table 1 clearly demonstrated that the path
A (Scheme 2) is reversible as opposed to the previous reports. It ap-
pears that, under the conditions employed in the literature (0 °C in
1% perchloric acid solution of H2O/1,4-dioxane, 2/3, v/v, for Shine’s
study),5a,5b the conversion of 2,20-diamino-1,10-binaphthyl to
dibenzo[c,g]carbazole would be too slow in the time frame, consid-
ering that our reaction of 3a to 5a takes 5 days even at an elevated
temperature (80 °C). In addition, their studies have effectively dis-
couraged any attempts to make benzo[c]carbazoles from 1,10-biar-
yl-2,20-diamines via condensation.
Entry
1
Time
5 (Yield)
1
2
3
4
5
6
7
8
9
1a (R@H)
1b (R = 5-Me)
8
8
8
8
8
8
8
12
12
5a (93%)
5b (93%)
5c (87%)
5d (85%)
5e (87%)
5f (91%)
5g (91%)
5h (trace)
5i (trace)
1c (R = 5-OMe)
1d (R = 3-OMe)
1e (R = 5-t-Bu)
1f (R = 5-Ph)
1g (R = 5-hexyl)
1h (R = 5-CO2Me)
1i (R = 5-COMe)
Various other 2,20-biaryldiamines 3b–3i were then prepared
and subjected to the condensation conditions to probe the scope.9
As shown in Table 2, the electronic nature of the substituent has a
critical effect on the reaction. While electron rich 2,20-biaryldiam-
ines (entries 1–6) afforded the corresponding benzo[c]carbazoles
in good to excellent yield, those with electron withdrawing group
(entries 7–8) gave no reaction and remained intact even after
12 days.
As the preceding [3,3]-sigmatropic rearrangement is also an
acid-catalyzed reaction, we combined it with the condensation
reaction so as to device
a one-pot synthetic protocol to
benzo[c]carbazoles from aryl hydrazides (Table 3). As expected,
diaryl hydrazides 1a–1g underwent [3,3]-sigmatropic rearrange-
ment and condensation reaction in a tandem fashion to afford
the corresponding benzo[c]carbazoles 5a–5g, when heated under
reflux in 1,4-dioxane (0.4 M HCl). Again, no reaction was observed
with the diaryl hydrazides bearing electron withdrawing group
(entries 8 and 9).
The ring closing condensation reaction was highly dependent
upon the type of aryl group. Under the same conditions, the con-
densation of 2,20-diamino-1,10-binaphthyl 4a was found to com-
plete within 3 h, affording dibenzo[c,g]carbazole 6a in 85% yield,
Table 1
Acid-catalyzed condensation of 3a
conditions
NH2
NH2
NH
R
R
R
R
3a
5a
0.4 M HCl (aq)
in 1,4-dioxane
Entry
Acid
Solvent/temp
Time
Yield
NH2
NH2
NH
R'
R'
1
2
3
4
5
6
7
8
9
0.4 M HCI
0.4 M HCI
0.4 M H2S04
6 M HCI
0.4 M HCI
0.4 M HCI
0.4 M HCI
0.4 M HCI
0.4 M HCI
EtOH, 78 °C
MeOH,64 °C
EtOH, 78 °C
EtOH, 78 °C
Isopropanol, 82 °C
tBuOH, 83 °C
n-Pentanol, 136 °C
Toluene, 110 °C
1,4-Dioxane, 100 °C
5 d
5 d
5 d
5 d
3 d
22 h
24 h
5 d
8 h
93%
89%
91%
92%
81%
76%
89%
45%
93%
reflux
R'
R'
3a
4a
9a
5 h
3 h
5 d
5a
6a
: R = H, R' = -CH=CH-
: R = R' = -CH=CH-
: R = R' = H
: 93%
: 85%
10a
: trace
Scheme 3. Condensation of 2,20-biaryldiamines.

B.-Y. Lim et al. / Tetrahedron Letters 52 (2011) 6015–6017
6017
whereas no reaction was observed with 2,20-biphenyl 9a even after
5 days (Scheme 3).
W. Synlett 2005, 127; (f) Smitrovich, J. H.; Davies, I. W. Org. Lett. 2004, 6, 533;
(g) Flanagan, S. R.; Harrowven, D. C.; Bradley, M. Tetrahedron Lett. 2003, 44,
1795; (h) Katrizky, A. R.; Wang, Z. J. Heterocycl. Chem. 1988, 25, 671; (i)
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2733; (j) Zander, M.; Franke, W. H. Chem. Ber. 1969, 102, 2728.
In summary, 2,20-diamino-1,10-biaryls were found to undergo
ring-closure condensation reaction to afford benzo[c]carbazoles,
contrary to the previous reports. Combined with the formation of
2,20-biaryldiamines from diaryl hydrazides via [3,3]-sigmatropic
rearrangement, it constitutes a new efficient synthetic method
for benzo[c]carbazoles and related compounds.
3. (a) Suh, S.-E.; Park, I.-K.; Lim, B.-Y. Eur. J. Org. Chem. 2011, 455; (b) Park, I.-K.;
Suh, S.-E.; Lim, B.-Y.; Cho, C.-G. Org. Lett. 2009, 11, 5454; (c) Lee, W.-J.; Kim, H.-
Y.; Cho, C.-G. Org. Lett. 2007, 9, 3185; (d) Kim, H.-Y.; Lee, W.-J.; Kang, H.-M.;
Cho, C.-G. Bull. Korean Chem. Soc. 2007, 28, 1821; (e) Kang, H.-M.; Kim, H.-Y.;
Jung, J.-W.; Cho, C.-G. J. Org. Chem. 2007, 72, 679; (f) Kang, H.-M.; Lim, Y.-K.;
Shin, I.-J.; Kim, H.-Y.; Cho, C.-G. Org. Lett. 2006, 8, 2047; (g) Lim, Y.-K.; Cho, C.-G.
Tetrahedron Lett. 2004, 45, 1857; (h) Lim, Y.-K.; Jung, J.-W.; Cho, C.-G. J. Org.
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Acknowledgment
This work was supported by the grant from Seoul R&BD Pro-
gram (PA100046M093212).
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Banthorpe, D. V. J. Chem. Soc. 1962, 2429.
Supplementary data
5. When heated at 80 °C, the proportion of 6a at low conversion was a little lower
than at high conversion, implying some thermal conversion (1–2%) of 4a into
6a. (a) Shine, H. J.; Gruszecka, E.; Subotkowski, W.; Brownawell, M.; Filippo, J.
S., Jr. J. Am. Chem. Soc. 1985, 107, 3218; (b) Shine, H. J.; Kupczyk-Subotkowska,
L.; Subotkowski, W. J. Am. Chem. Soc. 1985, 107, 6674.
Supplementary data (characterization of new benzo[c]carbaz-
oles by spectroscopic methods including IR, 1H, 13C NMR and
HRMS) associated with this article can be found, in the online ver-
sion, at doi:10.1016/j.tetlet.2011.09.001.
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fairly high reaction temperatures (>200 °C), resulting in the formation of
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9. For the preparation of diamine 3a–3j, see Ref. 3h.
10. Typical procedure, synthesis of benzo[c]carbazole 5a from 2,20-biaryldiamine
3a: To a sealed tube charged with 3a (100 mg, 0.43 mmol) was added 0.4 M
HCl in 1,4-dioxane (3 mL) at room temperature. The resulting mixture was
heated under reflux for 8 h. After completion of the reaction, mixture was
cooled to rt, neutralized with NaHCO3 (aq), and extracted with CH2Cl2 several
times. The combined organic solution was dried over Na2SO4, filtered,
concentrated, and purified by column chromatography (hexanes/CH2Cl2 = 1/
3) to afford 5a as a solid (87 mg, 93%).
11. Typical procedure, synthesis of benzo[c]carbazole 5a from diaryl hydrazide 1a:
To a sealed tube charged with 1a (100 mg, 0.30 mmol) was added 0.4 M HCl in
1,4-dioxane (3 mL) at room temperature. The resulting mixture was heated
under reflux for 8 h. After completion of the reaction, the reaction mixture was
cooled to rt, neutralized with NaHCO3 (aq), and extracted with CH2Cl2 several
times. The combined organic solution was dried over Na2SO4, filtered,
concentrated, and purified by column chromatography (hexanes/CH2Cl2 = 1/
3) to afford 5a (61 mg, 93%).
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