PDF herunterladen
Synlett 2020; 31(16): 1603-1607
DOI: 10.1055/s-0040-1707901
letter
© Georg Thieme Verlag Stuttgart · New York

Decarboxylative Bromination of Heteroarenes: Initial Mechanistic Insights

Pritesh R. Patel
a   School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, WV1 1LY, UK
,
Scott H. Henderson
b   Sussex Drug Discovery Centre, University of Sussex, Brighton, BN1 9RH, UK
,
Mark S. Roe
c   School of Life Sciences, University of Sussex, Brighton, BN1 9RH, UK
,
Mark A. Honey  ∗
d   School of Science, Faculty of Engineering and Science, University of Greenwich, Chatham, Kent, ME4 4TB, UK   eMail: m.a.honey@gre.ac.uk
› InstitutsangabenBiotechnology and Biological Sciences Research Council (BB/L017105/1).
Weitere Informationen

Publikationsverlauf

Received: 11. Juni 2020

Accepted after revision: 30. Juni 2020

Publikationsdatum:
17. Juli 2020 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik


Abstract

After an initial report from our laboratory describing metal-free decarboxylative halogenation of various azaheteroarenes, we set out to investigate the possible mechanism by which this chemistry occurs. Evidence from this mechanistic investigation suggests that this chemistry occurs via a radical pathway, with 1H NMR studies suggesting that the acidic substrates activate NBS.

Key words

decarboxylation - halogenation - reaction mechanism - bromosuccinimide - azahetarenes

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1707901.
  • Supporting Information
 

  • References and Notes

  • 1 Pozharskii AF, Soldatenkov AT, Katritzky AR. Heterocycles in Life and Society: An Introduction to Heterocyclic Chemistry, Biochemistry and Applications, 2nd ed. Wiley; Chichester: 2011
    CrossrefSuche in Google Scholar
  • 2 Heterocyclic Chemistry in Drug Discovery. Li JJ. Wiley; Hoboken: 2013
    Suche in Google Scholar
  • 3 Pathak TP, Miller SJ. J. Am. Chem. Soc. 2012; 134: 6120
    CrossrefPubMedSuche in Google Scholar
  • 4 Chung W.-J, Vanderwal CD. Angew. Chem. Int. Ed. 2016; 55: 4396
    CrossrefPubMedSuche in Google Scholar
  • 5 Bacsa I, Herman BE, Jójárt R, Herman KS, Wölfling J, Schneider G, Varga M, Tömböly C, Rižne TL, Szécsi M, Mernyák EJ. Enzyme Inhib. Med. Chem. 2018; 33: 1271
    CrossrefPubMedSuche in Google Scholar
  • 6 Mallinger A, Schiemann L, Rink C, Sejberg J, Honey MA, Czodrowski P, Stubbs M, Poeschke O, Busch M, Schneider R, Schwarz D, Musil D, Burke R, Urbahns K, Workman P, Wienke D, Clarke PA, Raynaud FI, Eccles SA, Esdar C, Rohdich F, Blagg J. ACS Med. Chem. Lett. 2016; 7: 573
    CrossrefPubMedSuche in Google Scholar
  • 7 Li F, Hu Y, Wang Y, Ma C, Wang J. J. Med. Chem. 2017; 60: 1580
    CrossrefPubMedSuche in Google Scholar
  • 8 Li J. J.; In Name Reactions; Springer, Berlin, 2009; 298; DOI: 10.1007/978-3-642-01053-8_131
  • 9 Fu Z, Li Z, Song Y, Yang R, Liu Y, Cai H. J. Org. Chem. 2016; 81: 2794
    CrossrefPubMedSuche in Google Scholar
  • 10 Jiang Q, Li H, Zhang X, Xu B, Su W. Org. Lett. 2018; 20: 2424
    CrossrefPubMedSuche in Google Scholar
  • 11 Hammamoto H, Umemoto H, Umemoto M, Ohta C, Fujita E, Nakamura A, Maegawa T, Miki Y. Heterocycles 2015; 91: 561
    CrossrefSuche in Google Scholar
  • 12 Perry GJ. P, Quibell JM, Panigrahi A, Larrosa I. J. Am. Chem. Soc. 2017; 139: 11527
    CrossrefPubMedSuche in Google Scholar
  • 13 Quibell JM, Perry GJ. P, Cannas DM, Larrosa I. Chem. Sci. 2018; 9: 3860
    CrossrefPubMedSuche in Google Scholar
  • 14 Henderson SH, West RA, Ward SE, Honey MA. R. Soc. Open Sci. 2019; 5: 180333
    CrossrefPubMedSuche in Google Scholar
  • 15 Bromination of Azahetarenecarboxylic Acids; General Procedure The appropriate carboxylic acid (0.280 mmol) was dissolved in the solvent (1.5 mL) and NBS (0.280 mmol) was added. The vessel was sealed and the mixture was stirred at rt for 16 h. H2O (10 mL) was added and the organic material was extracted with EtOAc (2 × 4 mL). The organic layers were combined, dried (MgSO4), filtered, and concentrated under reduced pressure. The crude residue was purified by chromatography (silica gel, EtOAc–PE or CH2Cl2–MeOH).
  • 16 3-Bromo-1H-indazole (Table [1], Entry 1) Colourless solid; yield: 36 mg (67%); mp 145–150 °C (Lit.14 142–143 °C). 1H NMR (400 MHz, CDCl3): δ = 1.57 (br s, 1 H, NH), 7.58 (m, 2 H, ArH), 7.39 (m, 1 H, ArH), 7.17 (m, 1 H, ArH). 13C NMR (100 MHz, CDCl3): δ = 141.3, 128.3, 123.1, 122.6, 121.9, 120.2, 110.7. HRMS (ESI): m/z [M + H]+ calcd for C7H6BrN2: 196.9709; found: 196.9717.
  • 17 Tanner DD, Ruo TC. S, Takiguchi H, Guillaume A, Reed DW, Setiloane BP, Tan SL, Meintzer CP. J. Org. Chem. 1983; 48: 2743
    CrossrefSuche in Google Scholar
  • 18 CCDC 1913779 contains the supplementary crystallographic data for 3-bromopyrazolo[1,5-b]pyridazine (Figure 1). The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
  • 19 Shimizu S, Imamura Y, Ueki T. Org. Process Res. Dev. 2014; 18: 354
    CrossrefSuche in Google Scholar
  • 20 Prakash GK. S, Mathew T, Hoole D, Esteves PM, Wang Q, Rasul G, Olah GA. J. Am. Chem. Soc. 2004; 126: 15770
    CrossrefPubMedSuche in Google Scholar
  • 21 Xue H, Tan H, Wei D, Wei Y, Lin S, Liang F, Zhao B. RSC Adv. 2013; 3: 5382
    CrossrefSuche in Google Scholar