Download PDF
Synlett 2006(19): 3237-3242  
DOI: 10.1055/s-2006-951562
LETTER
© Georg Thieme Verlag Stuttgart · New York

Regioselective Palladium-Catalyzed Arylation and Heteroarylation of ­Imidazo[1,2-a]pyridines

Jamal Koubachia,b, Saïd El Kazzoulia,b, Sabine Berteina-Raboin*a, Abderrahim Mouaddibb, Gérald Guillaumeta
a Institut de Chimie Organique et Analytique, UMR CNRS 6005, Université d’Orléans, BP 6759, 45067 Orléans Cedex 2, France
e-Mail: sabine.berteina@univ-orleans.fr;
b Faculté des Sciences et Techniques de Beni-Mellal, Université Caddi-Ayyad, BP 523, 23000 Beni-Mellal, Morocco
Further Information

Publication History

Received 26 July 2006
Publication Date:
23 November 2006 (online)

    Permissions and Reprints All articles of this category

Abstract

Palladium-catalyzed direct arylation and heteroarylation of imidazo[1,2-a]pyridines at the 3-position are described. The optimization of the reaction in conventional heating and the adaptation under microwaves irradiation is reported. The compatibility of the synthesis with the presence of bromo or chloro substituents in the 6-position was investigated.

Key words

palladium-catalyzed coupling - arylation - heteroarylation - imidazo[1,2-a]pyridines - microwave irradiation

23

Procedure for Synthesis of 6-Chloro-3- m -tolyl-imidazo[1,2- a ]pyridine 2 under Coventional Heating:
A mixture of 3-bromotoluene (0.12 mL, 0.98 mmol), 6-chloroimidazo[1,2-a]pyridine (0.1 g, 0.66 mmol), K2CO3 (0.18 g, 1.3 mmol), PPh3 (0.0073 g, 0.033 mmol) and Pd(OAc)2 (0.017 g, 0.063 mmol) in 1,4-dioxane (2 mL) was heated to 100 °C. The reaction was stirred for 48 h, and then the mixture was cooled to r.t. and extracted with CH2Cl2 (3 ×). The combined organic layer was dried over MgSO4 and concentrated under vacuum. The residue was purified by column chromatography on silica gel (EtOAc-PE) to give 6-chloro-3-m-tolylimidazo[1,2-a]pyridine(2) as an oil (146 mg, 92% yield). 1H NMR (250 MHz, CDCl3): δ = 2.45 (s, 3 H, CH3), 7.16 (dd, J = 1.9, 9.4 Hz, 1 H), 7.26 (d, J = 7.5 Hz, 1 H), 7.33 (m, 2 H), 7.43 (t, J = 7.5, 8.2 Hz, 1 H), 7.62 (d, J = 9.4 Hz, 1 H), 7.63 (s, 1 H), 8.34 (d, J = 1.9 Hz, 1 H). 13C NMR (62.5 MHz, CDCl3): δ = 22.1, 119.2, 121.6, 122.0, 125.7, 126.2, 129.2, 129.44 (2 × CH), 129.9 (2 × CH), 130.1, 133.9, 139.9.

26

Procedure for Synthesis of 6-Chloro-3- m -tolyl-imidazo[1,2- a ]pyridine 2 under Microwave Irradiation: The 6-chloroimidazo[1,2-a]pyridine (0.1 g, 0.66 mmol) was dissolved in 1,4-dioxane-EtOH (1.5 mL; 2:1) in a microwave vial equipped with a stir bar. 3-Bromotoluene (0.12 mL, 0.98 mmol), K2CO3 (0.18 g, 1.3 mmol), PPh3 (0.0073 g, 0.033 mmol) and Pd(OAc)2 (0.017 g, 0.063 mmol) were added under argon and subjected to microwave irradiation for 1 h at 130 °C with stirring. The reaction vessel was allowed to cool to r.t. and was diluted with CH2Cl2 (15 mL). The mixture was extracted with CH2Cl2 (3 ×). The combined organic layer was dried over MgSO4 and concentrated under vacuum. The crude material thus obtained was purified by column chromatography on silica gel (EtOAc-PE) to give 6-chloro-3-m-tolylimidazo[1,2-a]pyridine(2) as an oil (148 mg, 93% yield).