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

Antonio Abad; Consuelo Agulló; Ana Carmen Cuñat; Cristina Vilanova

doi:10.1055/s-2005-861844

Subscribe to RSS

Please copy the URL and add it into your RSS Feed Reader.

https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000084.xml

Share / Bookmark

Facebook X Linkedin Weibo

Download PDF

Synthesis 2005(6): 915-924
DOI: 10.1055/s-2005-861844

PAPER

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: antonio.abad@uv.es; e-Mail: consuelo.agullo@uv.es;

Further Information

Publication History

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

Abstract
Full Text
References

Permissions and Reprints All articles of this category

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

Key words

palladium - catalysis - cross-coupling - pyridines - ureidation

References

For example, see:
1a Dahl BH, Christophersen P, Engsig MT, Karsdal MA, and Foged NT. inventors; PCT Int. Appl. WO, 2004022529.

Google Scholar
1b Taylor CP, Price C, and Weber ML. inventors; US Patent, 6133299.

Google Scholar
1c Michael RP. Scandra JL. Charles PT. Fred MH. David LM. J. Med. Chem. 1990, 33: 54

Google Scholar
1d Henrie RN. inventors; PCT Int. Appl., WO 8702665.

Google Scholar
2a Honma T. Hayashi K. Aoyama T. Hashimoto N. Machida T. Fukasawa K. Iwama T. Ikeura C. Ikuta M. Suzuki-Takashashi I. Iwasawa Y. Hayama T. Nishimura S. Morishima H. J. Med. Chem. 2001, 44: 4515

Crossref Google Scholar
2b Honma T. Yoshizumi T. Hashimoto N. Hayashi K. Kawanishi N. Fukasawa K. Takai T. Ikeura C. Ikuta M. Suzuki-Takashashi I. Hayama T. Nishimura S. Morishima H. J. Med. Chem. 2001, 44: 4628

Crossref Google Scholar
3 Chieng C.-H. Leung M.-K. Su J.-K. Li G.-H. Liu Y.-H. Wang Y. J. Org. Chem. 2004, 69: 1866

Crossref Google Scholar
4 Yabuuchi K. Marfo-Owusu E. Kato T. Org. Biomol. Chem. 2003, 1: 3464

Crossref Google Scholar
5a Ling G. Chen J. Lu S. J. Chem. Res., Synop. 2003, 442

Crossref Google Scholar
5b Chen J. Ling G. Lu S. Tetrahedron 2003, 59: 8251 ; and references cited therein

Crossref Google Scholar
6 For a detailed recompilation of general procedures for synthesis of ureas, see: Gabriele B. Salerno G. Mancuso R. Costa M. J. Org. Chem. 2004, 69: 4741 ; and references cited therein

Crossref Google Scholar
7a Hartwig JF. Angew. Chem. Int. Ed. 1998, 37: 2046

Crossref Google Scholar
7b Wolfe JP. Wagaw S. Marcoux JF. Buchwald SL. Acc. Chem. Res. 1998, 31: 805

Crossref Google Scholar
8 Yin J. Buchwald SL. J. Am. Chem. Soc. 2002, 124: 6043

Crossref PubMed Google Scholar
9 Rivas FM. Giessert AJ. Diver ST. J. Org. Chem. 2002, 67: 1708

Crossref Google Scholar
10 Hartwig JF. Kawatsura M. Hauck SI. Shaughnessy KHM. Alcaraz-Roman L. J. Org. Chem. 1999, 64: 5575

Crossref PubMed Google Scholar
11 Shakespeare WC. Tetrahedron Lett. 1999, 40: 2035

Crossref Google Scholar
12 Bolm C. Hildebrand JP. J. Org. Chem. 2000, 65: 168

Google Scholar
13a Artamkina GA. Sergeev AG. Beletskaya IP. Tetrahedron Lett. 2001, 42: 4381

Google Scholar
13b Artamkina GA. Sergeev AG. Beletskaya IP. Zh. Org. Khim. 2002, 38: 563

Google Scholar
14 Sergeev AG. Artamkina GA. Beletskaya IP. Tetrahedron Lett. 2003, 44: 4719

Crossref Google Scholar
15 Ferraccioli R. Carenzi D. Synthesis 2003, 1383

Article in Thieme Connect Google Scholar
For additional examples of palladium-catalyzed C-N bond forming reactions, basically amination reactions, involving chloropyridines, see:
16a Arterburn JB. Corona C. Rao KV. Carlson KE. Katzenellenbogen JA. J. Org. Chem. 2003, 68: 7063

Crossref PubMed Google Scholar
16b Urgaonkar S. Nagarajan M. Verkade JG. Org. Lett. 2003, 5: 815

Crossref PubMed Google Scholar
16c Maes BUW. Loones KTJ. Lemière GLF. Dommisse RA. Synlett 2003, 1822

Crossref PubMed Google Scholar
16d Viciu MS. Kelly RA. Stevens D. Naud F. Studer M. Nolan S. Org. Lett. 2003, 5: 1479

Crossref PubMed Google Scholar
16e Burton G. Cao P. Li G. Rivero R. Org. Lett. 2003, 5: 4373

Crossref PubMed Google Scholar
16f Huang X. Anderson KW. Zim D. Jiang L. Klapars A. Buchwald SL. J. Am. Chem. Soc. 2003, 125: 6653

Crossref PubMed Google Scholar
16g Urgaonkar S. Xu J.-H. Verkade JG. J. Org. Chem. 2003, 68: 8416

Crossref PubMed Google Scholar
16h Viciu MS. Kissling RM. Stevens ED. Nolan SP. Org. Lett. 2002, 4: 2229

Crossref PubMed Google Scholar
16i Grasa GA. Viciu MS. Huang J. Nolan SP. J. Org. Chem. 2001, 66: 7729

Crossref PubMed Google Scholar
16j Huang X. Buchwald SL. Org. Lett. 2001, 3: 3417

Crossref PubMed Google Scholar
16k Harris MC. Buchwald SL. J. Org. Chem. 2000, 65: 5327

Crossref PubMed Google Scholar
16l Stauffer SR. Lee S. Stambuli JP. Hauck SI. Hartwig JF. Org. Lett. 2000, 2: 1423

Crossref PubMed Google Scholar
16m Wagaw S. Buchwald SL. J. Org. Chem. 1996, 61: 7240

Crossref PubMed Google Scholar
17 Abad A, Agulló C, Cuñat AC, Jiménez R, Navarro I, and Vilanova C. inventors; ES Patent, Appl. 200201347.
19 Argabright PA. Phillips BL. J. Heterocycl. Chem. 1970, 7: 999

Crossref Google Scholar
20 Takuzo H. Chem. Pharm. Bull. 1981, 29: 3706

Crossref Google Scholar
22 For the beneficial influence of water in related Pd-catalyzed reactions, see: Yin J. Zhao MM. Huffman MA. McNamara JM. Org. Lett. 2002, 4: 3481

Crossref Google Scholar
23 Arterburn JB. Rao KV. Ramdas R. Dible BR. Org. Lett. 2001, 3: 1351

Crossref Google Scholar
24 Prashad M. Mak XY. Liu Y. Repic O. J. Org. Chem. 2003, 68: 1163

Crossref PubMed Google Scholar
28 The related palladium-catalyzed amination reaction of some of these dichloropyridines has been previously studied, see: Joncker THM. Maes BUW. Lemière GLF. Dommisse R. Tetrahedron 2001, 57: 7027

Crossref Google Scholar
29 Danuta R. Spectrosc. Lett. 1993, 26: 227

Crossref Google Scholar
30 ScorŢanu E. Hitruc EG. Caraculacu AA. Eur. Polym. J. 2003, 39: 1051

Google Scholar
31a Cava MP. Bhattacharyya NK. J. Org. Chem. 1958, 23: 1287

Google Scholar
31b Mougin F. Mougin O. Trecourt F. Godard A. Queguiner G. Tetrahedron Lett. 1996, 37: 6696

Google Scholar
32 Ife RJ. Catchpole KW. Durant GJ. Ganellin CR. Harvey CA. Meeson ML. Ewen DAA. Parson ME. Slingsby BP. Theobald CJ. Eur. J. Med. Chem. 1989, 24: 249

Crossref Google Scholar
33 Kranenburg M. van der Burgt YEM. Kamer PCJ. van Leeuwen PWNM. Organometallics 1995, 14: 3081

Crossref Google Scholar
34 Chen J. Lu S. Appl. Catal., A 2004, 261: 199

Crossref Google Scholar
35 Chien C.-H. Leung M.-K. Su J.-K. Li G.-H. Liu Y.-H. Wang Y. J. Org. Chem. 2004, 69: 1866

Crossref Google Scholar
36 Meigh J.-P. Álvarez M. Joule JA. J. Chem. Soc., Perkin Trans. 1 2001, 2012

Crossref Google Scholar
37 Takeda M, Inage M, Wada HI, Tamaki H, and Ochiai T. inventors; Eur Patent, 268229.
38a The ABX systems were analyzed by the method of the effective Larmor frequencies, see: Günther H. NMR Spectroscopy, An Introduction John Wiley and Sons; New York: 1980. Chap V. p.160-170

Google Scholar
38b In addition, the gNMR computer program was also used: Budzelaar PHM. gNMR Computer Program Cherwell Scientific Publishing; Oxford UK: 2000.

Google Scholar

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.