Synthesis 2013; 45(4): 448-451
DOI: 10.1055/s-0032-1317933
practical synthetic procedures
© Georg Thieme Verlag Stuttgart · New York

N-Nitroso Group-Assisted Nucleophilic Aromatic Substitution of 6-Chloro­pyrimidines: A Facile and Efficient Synthesis of Pyrimidine-4,6- and -2,4-­diamines

Virginija Jakubkiene
Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, 03225 Vilnius, Lithuania   Fax: +370(5)2330987   Email: inga.cikotiene@chf.vu.lt
,
Justinas Zurba
Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, 03225 Vilnius, Lithuania   Fax: +370(5)2330987   Email: inga.cikotiene@chf.vu.lt
,
Inga Cikotiene*
Department of Organic Chemistry, Faculty of Chemistry, Vilnius University, Naugarduko 24, 03225 Vilnius, Lithuania   Fax: +370(5)2330987   Email: inga.cikotiene@chf.vu.lt
› Author Affiliations
Further Information

Publication History

Received: 19 October 2012

Accepted after revision: 28 November 2012

Publication Date:
21 December 2012 (online)


Abstract

An N-nitroso group was used to activate chloropyrimidines toward nucleophilic substitution by amines. This permitted a simple, one-pot, high-yielding synthesis of pyrimidine-4,6- and -2,4-diamines.

Supporting Information

 
  • References

    • 1a Brown DJ, Evans RF, Cowden WB, Fenn MD. The Pyrimidines . Wiley; New York: 1994
    • 1b Undheim K, Benneche T In Comprehensive Heterocyclic Chemistry II . Katritzky AR, Rees CW, Scriven EF. Pergamon; Oxford: 1996
    • 2a Hitchings GH. Angew. Chem., Int. Ed. Engl. 1989; 28: 879
    • 2b Hitchings GH. Rev. Port. Farm. 1991; 41: 21
    • 2c Sirawaraporn W, Sertsrivanich R, Booth RG, Hansch C, Neal RA, Santi DV. Mol. Biochem. Parasitol. 1988; 31: 79
    • 2d Deng X, Okram B, Ding Q, Zhang J, Choi Y, Adrián FJ, Wojciechowski A, Zhang G, Che J, Bursulaya B, Cowan-Jacob SW, Rummel G, Sim T, Gray NS. J. Med. Chem. 2010; 53: 6934
    • 2e William AD, Lee AC.-H, Goh KC, Blanchard S, Poulsen A, Teo E, Nagaraj H, Lee CP, Wang H, Williams M, Sun ET, Hu C, Jayaraman R, Pasha MK, Ethirajulu K, Wood JM, Dymock BW. J. Med. Chem. 2012; 55: 169
    • 2f Lagoja IM. Chemistry & Biodiversity 2005; 2: 1
    • 2g Cheng CC, Roth B. Prog. Med. Chem. 1982; 19: 267
    • 2h Rewcastle GW, Denny WA, Showalter HD. H. Curr. Org. Chem. 2000; 4: 679
    • 2i Arvanitis AG, Gilligan PJ, Chorvat RJ, Cheeseman RS, Christos TE, Bakthavatchalam R, Beck JP, Cocuzza AJ, Hobbs FW, Wilde RG, Arnold C, Chidester D, Curry M, He L, Hollis A, Klaczkiewicz J, Krenitsky PJ, Rescinito JP, Scholfield E, Culp S, De Souza EB, Fitzgerald L, Grigoriadis D, Tam SW, Wong YN, Huang S.-M, Shen HL. J. Med. Chem. 1999; 42: 805
    • 2j Kinnamon KE, Engle RR, Poon BT, Ellis WY, McCall JW, Dzimianski MT. Ann. Trop. Med. Parasitol. 1999; 93: 851
    • 3a Wang LX, Wang DX, Huang ZT, Wang MX. J. Org. Chem. 2010; 75: 741
    • 3b Samson D, Daltrozzo E. Helv. Chim. Acta 2011; 94: 46
    • 4a Whitehead CW, Traverso JJ. J. Am. Chem. Soc. 1958; 80: 2185
    • 4b Rose FL, Swain G. J. Chem. Soc. 1945; 689
    • 4c Muller J.-C, Ramuz H. Helv. Chim. Acta 1982; 65: 1445
    • 5a Whitehead CW, Traverso JJ. J. Am. Chem. Soc. 1960; 82: 3971
    • 5b Andersen DL, Chang CH, Falsey JR, Frohn MJ, Hong F.-T, Liao H, Liu L, Lopez P, Retz DM, Rishton GM, Rzasa RM, Siegmund A, Tadesse S, Tamayo N, Tegley CM. US 2006069110, 2006
    • 6a Maggiolo A, Phillips AP, Hitchings GH. J. Am. Chem. Soc. 1951; 73: 106
    • 6b Guillier F, Roussel P, Moser H, Kane P, Bradley M. Chem. Eur. J. 1999; 5: 3450
    • 6c Mousseau JJ, Xing L, Tang N, Cuccia LA. Chem. Eur. J. 2009; 15: 10030
    • 7a Wang K, Wu L, Qin Z, Yan X, Li X, Chen H, Zhang P, Zhang J. Bioorg. Med. Chem. Lett. 2011; 21: 916
    • 7b Luo G, Chen L, Poindexter GS. Tetrahedron Lett. 2002; 43: 5739
    • 7c Mihovilovic M, Schnuerch M, Koley M, Hilber K, Koenig X. WO 2011079343, 2011
    • 7d Samadi A, Silva D, Chioua M, do Carmo Carreiras M, Marco-Contelles J. Synth. Commun. 2011; 41: 2859
    • 8a Maltese M. J. Org. Chem. 1995; 60: 2436
    • 8b Lawson JE, Dennis RD. US 4021562, 1977
  • 9 Jakubkienė V, Čikotienė I. Tetrahedron 2012; 68: 2294

    • Aromatic amines show very poor reactivity in nucleophilic substitution reactions with nonactivated chloropyrimidines; see:
    • 10a Guillier F, Roussel P, Moser H, Kane P, Bradley M. Chem. Eur. J. 1999; 5: 3450
    • 10b Barillari C, Barlocco D, Raveglia LF. Eur. J. Org. Chem. 2001; 4737
    • 11a Marquais-Bienewald S, Holzl W, Preuss A, Mehlin A. US 2006188453, 2006
    • 11b Gunar VJ, Ovechkina LF, Arutyunyan EA, Mikhailopulo JA, Zavyalov SI, Kulaeva ON. Izv. Akad. Nauk SSSR, Ser. Khim. 1969; 2772
  • 12 Kano S, Tanaka Y, Sugino E, Shibuya S, Hibino S. Synthesis 1980; 741
  • 13 Cho BP, Blankenship LR, Moody JD, Doerge DR, Beland FA, Culp SJ. Tetrahedron 2000; 53: 7379