The double N-arylation of primary amines: Toward multisubstituted carbazoles with unique optical properties

Article abstract of DOI:10.1002/anie.200250648

A powerful method: A variety of sterically crowded, substituted carbazoles have been prepared from anilines and biphenyl compounds (see scheme). The method enabled the preparation of 2,2′-dicarbazolyl-1,1′-biaryl compounds, which show excimer (or exciplex) emissions with significant solvent dependency.

Full text of DOI:10.1002/anie.200250648

Angewandte
Chemie
Synthesis of Carbazoles
The Double N-Arylation of Primary Amines:
Toward Multisubstituted Carbazoles with Unique
Optical Properties**
Kyoko Nozaki,* Keita Takahashi, Koji Nakano,
Tamejiro Hiyama, Hong-Zhi Tang, Michiya Fujiki,
Shigehiro Yamaguchi, and Kohei Tamao
Carbazole has been known as an important intermediate for
artificial dyes and has recently attracted much attention
because of its unique photophysical properties.[1] The intro-
duction of substituents onto carbazole is essential to optimize
its absorption, luminescence, and electronic properties.[2] For
the synthesis of multisubstituted carbazole derivatives, the
construction of the carbazole ring itself is highly desired.[3]
[*] Prof. Dr. K. Nozaki, K. Nakano
Department of Chemistry and Biotechnology
Graduate School of Engineering, The University of Tokyo
Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)
Fax: (+81)3-5841-7261
E-mail: nozaki@chembio.t.u-tokyo.ac.jp
Prof. Dr. K. Nozaki, Dr. S. Yamaguchi
PRESTO-JST (Japan)
JST, Hon-cho, Kawaguchi, Saitama 332-0012 (Japan)
K. Takahashi, Prof. Dr. T. Hiyama
Department of Material Chemistry
Graduate School of Engineering, Kyoto University
Yoshida, Sakyo-ku, Kyoto 606-8501 (Japan)
Dr. H.-Z. Tang, Prof. Dr. M. Fujiki
CREST-JST
JST, Hon-cho, Kawaguchi, Saitama 332-0012 (Japan)
Prof. Dr. M. Fujiki
Graduate School of Materials Science
Nara Institute of Science and Technology
Takayama, Ikoma, Nara 630-0101 (Japan)
Dr. S. Yamaguchi, Prof. Dr. K. Tamao
Institute for Chemical Research, Kyoto University
Uji, Kyoto 611-0011 (Japan)
[**] We thank the Ministry of Education, Culture, Sports, Science, and
Technology, Japan, for the Grants-in-Aid for COE Research on
Elements Science, No. 12CE2005.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2003, 42, 2051 – 2053
DOI: 10.1002/anie.200250648
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2051

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Table 1: Synthesis of carbazoles 3a–l and their fluorescence data.
The availability of substituted 2,2’-dihalobiphenyl com-
pounds[4] prompted us to study the double N-arylation
strategy to synthesize multisubstituted carbazoles as de-
scribed in Scheme 1. In contrast to conventional carbazole-
Entry
1
2
3
Yield [%][a]
lmax [nmÀ1] (ff)[b]
1
2
3
4
5
6
7
8
9
a
a
a
a
a
a
b
b
c
c
d
a
a
b
c
d
e
f
a
b
a
b
a
g
a
b
c
d
e
f
g
h
i
86A
90A
53A
76A
73A
67B
92A
88A
84C
8D
342 (0.23)
383 (0.18)
349 (0.42)
373 (0.18)
361 (0.20)
345 (0.19)
347 (0.21)
386 (0.24)
R2
R2
5
n
4
2
n
3
1
3
[Pd2(dba)3]
phosphane
4
6
X
R1 NH2
R1
N
8
+
X
base
6'
5'
[c]
5
–
–
[c]
6
10
11
12
j
k
l
3'
7
R2
4'
R2
n
n
28A
35A
347 (0.30)
[c]
2
1a: R1 = C6H5
X = Br; R n = H
3a-k
2a:
2b:
2c:
2d:
2e:
2f:
–
2
1b:R1 = 4-MeO-C6H4
1c: R1 = 4-NO2-C6H4
1d:R1 = n-C8H17
X = Br; R n = 5,5'-(MeO)2
[a] Reaction conditions A–D are noted as superscripts. Condition A: 1
(1.00 mmol), 2 (1.20 mmol), [Pd2(dba)3] (0.05 mmol), tBu3P
(0.20 mmol), NaOtBu(2.40 mmol), toluene (2 mL), 80 8C. Reaction
times are specified in the Supporting Information. Condition B: 1
(1.00 mmol), 2 (2.00 mmol), [Pd2(dba)3] (0.05 mmol), tBu3P
(0.20 mmol), NaOtBu(2.40 mmol), toluene (2 mL), 80 8C, 24 h, then
1008C, 24 h. Condition C: 1 (1.00 mmol), 2 (1.20 mmol), [Pd2(dba)3]
(0.05 mmol), (S)-binap (0.15 mmol), Cs2CO3 (2.80 mmol), toluene
(2 mL), 1008C, 72 h. Condition D: 1 (1.00 mmol), 2 (1.20 mmol),
[Pd2(dba)3] (0.05 mmol), 2-[di(tert-butyl)phosphanyl]biphenyl
(0.20 mmol), and K3PO4 (2.80 mmol), dimethoxyethane (2 mL), 1008C,
72 h. [b] Fluorescence spectra were measured in cyclohexane. [c] No
clear peaks were observed for 3i, 3j, 3l.
2
X = Br; R n = 4,4',5,5'-Me4
2
X = Br; R n = 4,4',5,5'-(MeO)4
2
X = I ; R n = 4,4'-(CF3)2
X = Br; R2n = 4,4'-(MeO)2
S
S
S
Br
+
NH2
N
Br
S
1a
2g
3l
Scheme 1. The double N-arylation of primary amines in the synthesis of
carbazoles (dba=trans,trans-dibenzylideneacetone).
ring construction strategies starting from ortho-aminobi-
phenyl compounds,[4b,5,6] the nitrogen atom comes from
primary amines in the present double N-arylation strategy.
Although the double arylation of primary amines was
successfully accomplished for the synthesis of triarylamines,
the method has not yet been applied to the synthesis of
carbazoles.[7] Herein we report that the present method is
especially effective for the synthesis of sterically crowded 2,2’-
dicarbazolyl-1,1’-biaryl compounds 5a and 5b, which could
not be synthesized by the simple arylation of carbazole
(Scheme 2). The unique optical properties of 5a and 5b are
also disclosed.
Based on the recent intensive studies on the catalytic N-
arylation of amines with organic halides,[8] [Pd2(dba)3]/tBu3P/
NaOtBu (condition A),[9] was first employed for our purpose.
Representative results are summarized in Table 1, which also
contains the fluorescence data of the resulting carbazoles
3a–l. The reaction was applicable to various dihalobiphenyl
compounds 2a–e (Table 1, entries 1–5). 4,4’-Dimethoxy-2,2’-
dibromobiphenyl (2 f) showed a lower reactivity and was used
in excess at a higher temperature (Table 1, entry 6, condi-
tion B). Substituted anilines can be employed. 4-Methoxyani-
line (1b) was preferable (Table 1, entries 7 and 8), whereas
the reaction was retarded with 4-nitroaniline (1c). In such a
case, a combination of binap[10] and Cs2CO3 was effective
(Table 1, entry 9, condition C). The reaction of 1c with 2b did
not proceed under conditions A, B, or C. The coupling
product was finally obtained in a small amount by using 2-
di(tert-butyl)phosphanylbiphenyl[11] and K3PO4 in DME
(Table 1, entry 10, condition D). A lower reactivity was
observed with the aliphatic amine 1d (Table 1, entry 11). A
dithienopyrrole, 3g, could be synthesized through double N-
arylation starting from bithiophene 2g (Table 1, entry 12).
The method is especially effective for sterically hindered
aryl amines as shown in Scheme 2. Starting from (S)-2,2’-
diamino-1,1’-binaphthyl (4a) and more than 2 molar amounts
of 2,2’-dibromobiphenyl (2a), N-arylation took place four
times per molecule of 4a to afford the desired chiral
dicarbazolylbinaphthyl 5a in 82% yield. Tri(tert-butyl)phos-
phane was the ligand of choice. Dicarbazolylbiphenyl 5b was
similarly prepared from 2,2’-diaminobiphenyl (4b) and 2a.
An alternative approach to 5 in which 2,2’-dibromo-1,1’-
binaphthyl (racemic, 6) or 2,2’-dibromobiphenyl (2a) were
treated with more than 2 molar amounts of carbazole failed.
A Pd/phosphane[12] catalyst gave a monocoupling product, 2-
carbazolyl-2’-bromobinaphthyl, in less than 8% yield from 6.
The use of a Ni or Cu catalyst resulted in no reaction.[13]
The fluorescence spectra of 5a and 5b both showed broad
peaks, suggesting the formation of intramolecular excimers
and/or exciplexes.[14,15] Furthermore, the fluorescence wave-
lengths of 5a and 5b significantly depend on the solvent
Scheme 2. Synthesis and optical properties of dicarbazolylbiaryl compounds 5a
and 5b. a) Reaction conditions: 4 (0.50 mmol), 2a (1.20 mmol), [Pd2(dba)3]
(0.050 mmol), tBu3P (0.20 mmol), NaOtBu(2.40 mmol), toluene (2.0 mL),
808C, 24 h. b) Fluorescence spectra were measured in cyclohexane (excited at
295 nm).
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Angewandte
Chemie
polarity.[16] When 5a was excited at 295 nm, the emission peak
underwent a red shift as the solvent polarity increased from
cyclohexane (dielectric constant 2.0) to chloroform (4.7), and
to acetonitrile (37.5) (Figure 1). This observation corresponds
to the energetic stabilization of the polar excimer (and/or
exciplex) by solvation.
estimated with reference to p-terphenyl (ff = 0.87 in cyclohexane
when excited at 265 nm)).
Received: November 27, 2002 [Z50648]
Keywords: biaryls · luminescence · nitrogen heterocycles ·
.
palladium
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In conclusion, we have presented a new strategy toward
carbazole synthesis. Dicarbazolylbiaryl compounds 5a and
5b, which could not be synthesized by other methods,
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Experimental Section
5a: A solution of tri(tert-butyl)phosphane (40 mg, 0.20 mmol) in
toluene (1.0 mL) was added to a mixture of 2a (374 mg, 1.20 mmol),
4a (142 mg, 0.50 mmol), sodium tert-butoxide (231 mg, 2.40 mmol),
and [Pd2(dba)3] (46 mg, 0.050 mmol) in toluene (1.0 mL). After
heating under argon at 808C for 24 h, the reaction mixture was
concentrated, and purification by silica-gel column chromatography
afforded 5a (240 mg, 82%) as colorless needles. M.p. 277.6–278.18C;
Rf = 0.38 (hexane/EtOAc = 5:1); [a]2D5 = À274.5 (c = 0.42, CHCl3);
> 99% ee (HPLC: Chiralcel OD, hexane/iPrOH = 99:1, tR = 7.9 min
1
(R), 10.4 min (S)); H NMR (200 MHz, CDCl3): d = 7.95 (d, 2H, J =
8.0 Hz), 7.88–7.78 (m, 6H), 7.68–7.51 (m, 6H), 7.14 (d, 2H, J =
8.8 Hz), 6.96 (dd, 2H, J = 7.2, 7.2 Hz), 6.85–6.60 (m, 6H), 6.45 (dd,
2H, J = 7.7, 7.7 Hz), 5.57 ppm (d, 2H, J = 8.2 Hz); 13C NMR
(50 MHz, CDCl3): d = 142.1, 140.8, 135.8, 134.3, 133.0, 131.4, 128.6,
128.1, 127.3, 126.7, 126.3, 125.4, 124.4, 123.7, 119.6, 119.5, 119.2, 118.8,
110.6, 110.2 ppm; MS (FAB+): m/z (%): 584 (148.7), 585 (122.4), 586
(44.6), 587 (12.4); HRMS (FAB+): calcd for C44H28N2: M+ 584.2252M,
found: m/z 584.2257; elemental analysis: calcd for 5a·CHCl3
(C45H29N2Cl3): C 76.76, H 4.15; found: C 76.82, H 4.14; absorption
(lmax nm (loge)): in cyclohexane: 341 (3.89), 294 (4.51), 229 (5.20); in
CHCl3: 343 (3.78), 305 (4.47), 297 (4.45); in CH3CN: 340 (4.01), 293
(4.48), 228 (5.20); emission: lmax nm in cyclohexane: 407 (ff = 0.21);
in CHCl3: 430 (ff = 0.18); in CH3CN: 442 (ff = 0.13) (quantum yields
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