ORGANIC
LETTERS
2003
Vol. 5, No. 7
979-982
Novel Route to Azobenzenes via
Pd-Catalyzed Coupling Reactions of Aryl
Hydrazides with Aryl Halides, Followed
by Direct Oxidations†
Young-Kwan Lim, Kang-Sang Lee, and Cheon-Gyu Cho*
Department of Chemistry, Hanyang UniVersity, Seoul 133-791, Korea
Received November 20, 2002
ABSTRACT
N-Boc aryl hydrazines undergo Pd-catalyzed coupling reactions with aryl halides to provide N-Boc diaryl hydrazines in excellent yields. The
resulting N-Boc diaryl hydrazines were directly oxidized with NBS/pyridine in CH Cl2 at room temperature to the azobenzenes.
2
Due to their characteristic color and photoresponsive proper-
ties, azobenzenes have gained much interest over the past
years. Various types of azobenzenes were prepared and
studied for their possible applications in the area of nonlinear
optics, optical storage media, chemosensors, and photo-
chemical switches.1 Diazo bonds in azobenzenes undergo
reversible cis-trans isomerizations, causing changes of
molecular geometry when subjected to visible light. Also
investigated was their potential use as a diagnostic probe
for the visualization of amyloid plaques in the brains of
mentally deteriorating patients for a definite diagnosis of
Alzheimer’s disease.2
Azobenzenes are commonly prepared from aromatic
amines via formation of diazonium ion, followed by diazo
coupling with arylamine or alcohol.3 Less commonly used,
but often more effective, is the coupling of nitroso arene
with arylamine.4 Symmetrical azobenzenes can be prepared
from either direct reduction of nitroarene or oxidation of
aromatic amine.5 In general, the starting arylamines or
alcohols need to be readily available and also sufficiently
soluble in acidic media.
Adopting well-developed transition metal-catalyzed ami-
nation reactions, we hypothesized a new approach for those
compounds starting from a hydrazine and more readily
available aryl halides. In principle, consecutive couplings of
a hydrazine6 with two molecules of aryl halides, followed
† Dedicated to Professor Gary H. Posner on the occasion of his 60th
birthday.
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Org. Lett. 2002, 4, 3603. (c) Wang, S.; Advincula, R. C. Org. Lett. 2001,
3, 3831. (d) DiCesare, N.; Lakowicz, J. R. Org. Lett. 2001, 3, 3891. (e)
Harvey, A. J.; Abell, A. D. Tetrahedron 2000, 56, 9763. (f) Burland, D.
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ReV. 1989, 89, 1915.
(3) For review of azo dyes, see: (a) Zollinger, H. Diazo Chemistry I.
Aromatic and Heteroaromatic Compounds; VCH: New York, 1994. (b)
Hegarty, A. F. In The Chemistry of Diazonium and Diazo Groups; Patai,
S., Ed.; Wiley: New York, 1978; Part 2, pp 545-551. (c) The Chemistry
of Synthetic Dyes; Venkataraman, K., Ed.; Academic Press: New York,
1970; Vols. 1-7.
(4) (a) Davey, M. H.; Lee, V. Y.; Miller, R. D.; Marks, T. J. J. Org.
Chem. 1999, 64, 4976. (b) Szele, I.; Zollinger, H. Top. Curr. Chem. 1983,
112, 1.
(5) (a) Wada, S.; Urano, M.; Suzuki, H. J. Org. Chem. 2002, 67, 8254.
(b) Leyva, E.; Platz, M. S.; Persy, G.; Wirz, J. J. Am. Chem. Soc. 1986,
108, 3783.
(2) (a) Zhen, W.; Han, H.; Anguiano, M.; Lemere, C.; Cho, C.-G.;
Lansbury, P. T. Jr. J. Med. Chem. 1999, 42, 2805-2815. (b) Han, H.; Cho,
C.-G.; Lansbury, P. T. Jr. J. Am. Chem. Soc. 1995, 118, 4506.
(6) Song, J. J.; Yee, N. K. Org. Lett. 2000, 2, 519.
10.1021/ol027311u CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/12/2003