Palladium/P(t-Bu)3-catalyzed synthesis of N-aryl azoles and application to the synthesis of 4,4',4''-tris(N-azolyl)triphenylamines

Article abstract of DOI:10.1016/S0040-4039(99)02096-1

Palladium/P(t-Bu)₃ catalyzed the coupling of aryl halides with azoles such as pyrrole, indole, and carbazole, effectively. K₂CO₃ and Rb₂CO₃ worked very well as bases, whereas Cs₂CO₃ and t-BuONa gave only trace yields of products. Triazolyl compounds such as TCTA were also synthesized.

Full text of DOI:10.1016/S0040-4039(99)02096-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 481–483
Palladium/P(t-Bu)3-catalyzed synthesis of N-aryl azoles
and application to the synthesis of
4,40,400-tris(N-azolyl)triphenylamines
Makoto Watanabe,∗ Masakazu Nishiyama, Toshihide Yamamoto and Yasuyuki Koie
Yokkaichi Research Laboratory, Tosoh Corporation, 1-8 Kasumi, Yokkaichi, Mie 510-8540, Japan
Received 1 October 1999; revised 1 November 1999; accepted 2 November 1999
Abstract
Palladium/P(t-Bu)3 catalyzed the coupling of aryl halides with azoles such as pyrrole, indole, and carbazole,
effectively. K2CO3 and Rb2CO3 worked very well as bases, whereas Cs2CO3 and t-BuONa gave only trace yields
of products. Triazolyl compounds such as TCTA were also synthesized. © 2000 Elsevier Science Ltd. All rights
reserved.
Keywords: amination; palladium catalysts; phosphine; azoles; arylation.
N-Aryl azoles have attracted attention as hole transport molecules for organic light-emitting diodes
(LEDs)1 and biologically active compounds.2 N-Arylation of azole compounds was carried out by metal-
mediated reactions such as the Ullmann coupling,1,3 aromatic nucleophilic substitution using KF/Al2O3,4
Cr(CO)3 complexed haloarenes as substrates,2 and Pd- and Cu-catalyzed arylation.5 However, the
employment of aprotic polar solvents such as DMF and a stoichiometric amount of Cr(CO)3, and harsh
reaction conditions diminish the applicability of these methods, especially for large-scale production.
On the other hand, palladium/DPPF-catalyzed N-arylation of azoles with aryl bromides using Cs2CO3
or t-BuONa was recently reported.6 The reaction with electron-poor aryl bromides took place in the
presence of 1 mol% of Pd(OAc)2, whereas catalytic activity was low on reaction with bromobenzene and
electron-rich aryl bromides requiring 5 mol% of palladium.
We showed that palladium/P(t-Bu)3 was highly active and selective in N-arylation of amines with aryl
halides.7 We also disclosed tin-mediated synthesis of N-aryl azoles using the same catalyst.8 Although
high catalytic activity (0.25 mol% of Pd per halogen atom of aryl halides) and the synthesis of elaborate
N-aryl azoles were attained, the employment of a stoichiometric amount of a tin compound is a drawback.
We herein report highly efficient tin-free N-arylation of azoles with aryl halides using palladium and P(t-
Bu)3.
∗
Corresponding author. Tel: +81 593 63 1374; fax: +81 593 63 2641; e-mail: m_wata@tosoh.co.jp (M. Watanabe)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02096-1
tetl 16024

482
(1)
Table 1
Palladium-catalyzed synthesis of N-aryl azolesa
Palladium-catalyzed synthesis of N-aryl azoles is summarized in Eq. (1) and Table 1. Reaction of
bromobenzene with carbazole was examined with various kinds of bases. N-Phenylation proceeded using
carbonates, and the yields increased in the order of increase of basicity (runs 1–3). However, use of
Cs2CO3 gave no substantial amount of the product, nor did t-BuONa (runs 4 and 5). This outcome shows
a sharp contrast to DPPF-ligated palladium catalyst, which allows the use of Cs2CO3 and t-BuONa.6
In our catalytic system, K2CO3 and Rb2CO3 worked very well. The reason is still unclear but the

483
employment of the stronger bases may cause formation of a significant amount of metal carbazolyl,
which is assumed to deactivate the palladium catalyst. Although employing 1 equivalent of a base gave
an acceptable yield, the reaction was accelerated by using 3 equivalents of the base. N-Phenylation of
indole and pyrrole proceeded similarly (runs 6 and 7). Reactions of aryl halides bearing substituents with
azoles were investigated. Both electron-poor and -rich aryl halides were converted into N-aryl azoles in
good to high yields (runs 8–11). This electron-rich catalyst can also couple p-chlorobenzaldehyde with
carbazole (run 12).
As described above, K2CO3 and Rb2CO3 promoted good activity in this reaction and the use of K2CO3
is more preferable practically. Therefore, we examined the synthesis of triazole derivatives such as TCTA
in the presence of 3 mol% of Pd(OAc)2 and 9 equivalents of K2CO3 to aryl trihalide. Reactions of
3 equivalents of pyrrole and carbazole with tri(4-bromophenyl)amine were carried out in o-xylene at
120°C for 24 h to afford 4,40,400-tris(N-pyrrolyl)triphenylamine (TPTA, 1)9 in 65% yield and 4,40,400-
tris(N-carbazolyl)triphenylamine (TCTA, 2)1a,10 in 59% yield, respectively. Thus, the catalytic system
consisting of palladium and P(t-Bu)3 can provide a more efficient and practical synthetic method of
N-aryl azoles.
References
1. (a) Kuwabara, Y.; Ogawa, H.; Inada, H.; Noma, N.; Shirota, Y. Adv. Mater. 1994, 6, 677-679. (b) Hu, N.-X.; Xie, S.; Popovic,
Z.; Ong, B.; Hor, A.-M. J. Am. Chem. Soc. 1999, 121, 5097-5098.
2. Maiorana, S.; Baldoli, C.; Buttero, P. D.; Ciolo, M. D.; Papagni, A. Synthesis 1998, 735-738 and references cited therein.
3. Arylation of imidazoles was recently reported, see: Kiyomori, A.; Marcoux, J.-F.; Buchwald, S. L. Tetrahedron Lett. 1999,
40, 2657-2660.
4. Smith III, W. J.; Sawyer, J. S. Tetrahedron Lett. 1996, 37, 299-302.
5. Arylation of benzotriazole was reported, see: Beletskaya, I. P.; Davydov, D. V.; Moreno-Manas, M. Tetrahedron Lett. 1998,
39, 5617-5620.
6. Mann, G.; Hartwig, J. F.; Driver, M. S.; Rivas, C. F. J. Am. Chem. Soc. 1998, 120, 827-828.
7. (a) Palladium/P(t-Bu)3 highly repressed debromination of aryl bromides in the reaction with piperazine, see: Nishiyama, M.;
Yamamoto, T.; Koie, Y. Tetrahedron Lett. 1998, 39, 617-620. (b) Yamamoto, T.; Nishiyama, M.; Koie, Y. Tetrahedron Lett.
1998, 39, 2367-2370.
8. Watanabe, M.; Nishiyama, M.; Yamamoto, T.; Koie, Y. Speciality Chemicals 1998, 18, 445-450.
9. Compound 1 was isolated by column chromatography on SiO2 (hexane:AcOEt). 1H NMR (400 MHz, CDCl3): δ=6.32 (d,
J=2.0 Hz, 6H), 7.04 (d, J=2.0 Hz, 6H), 7.13 (d, J=6.1 Hz, 6H), 7.29 (d, J=6.1 Hz, 6H).
10. Compound 2 was isolated by reprecipitation from THF–MeOH. In Ref. 1a, 2 was prepared from triiodotriphenylamine with
carbazole by the Ullmann protocol.