Synthesis 2005(6): 915-924  
DOI: 10.1055/s-2005-861844
PAPER
© Georg Thieme Verlag Stuttgart · New York

Regioselective Preparation of Pyridin-2-yl Ureas from 2-Chloropyridines Catalyzed by Pd(0)

Antonio Abad*, Consuelo Agulló*, Ana Carmen Cuñat, Cristina Vilanova
Departamento de Química Orgánica, Facultad de Químicas, Universidad de Valencia, C/ Dr. Moliner 50, 46100 Burjassot, Valencia, Spain
Fax: +34(96)3544328; e-Mail: [email protected]; e-Mail: [email protected];
Further Information

Publication History

Received 17 November 2004
Publication Date:
10 March 2005 (online)

Abstract

The palladium-catalyzed ureidation reaction of 2-chloropyridines can be regioselectively performed in good yield, with both aryl and aliphatic ureas, using xantphos as the ligand, Pd(OAc)2 as the source of palladium, NaOt-Bu/H2O or NaOH/H2O as the base, and dioxane as the solvent

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18

A preliminary account of this work was presented at the XXIX Reunión Bienal de la Real Sociedad Española de Química, July 7-11, 2003, Madrid, Spain (abstr. no. S1P1001).

21

Other minor side-products observed with long reaction times were pyridin-2-ylamine and N,N′-dipyridin-2-yl urea, probably originating, as shown by independent control experiments, from disproportionation of the initially formed pyridin-2-yl urea 3a.

25

In fact, reaction of 3-chloropyridine with aniline [Pd(OAc)2 (3 mol%), xantphos (6 mol%), NaOt-Bu (1.4 equiv), H2O (1.4 equiv), dioxane, 100 °C, 19 h] gave a 66% yield of N-phenyl-N′(pyridin-3-yl)amine(7b).

26

Appropriate experimental controls showed that nearly 70-80% of the urea 3c was transformed into a mixture of disproportionated products, mainly aniline, diphenylurea and 4-aminopyridine, when treated under the coupling reaction conditions (as in entry 6 of Table [1] , but omitting the phenylurea) for 17 h.

27

See ref. [7a] for a detailed discussion of the mechanism of palladium-catalyzed amination and related C-N bond-forming reactions.