Synlett 2020; 31(06): 632-634
DOI: 10.1055/s-0039-1690828
cluster
© Georg Thieme Verlag Stuttgart · New York

1,2,4-Triphenylpyrroles: Synthesis, Structure and Luminescence Properties

Joana R. M. Ferreira
a   QOPNA, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal   Email: sguieu@ua.pt
,
Raquel Nunes da Silva 
a   QOPNA, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal   Email: sguieu@ua.pt
b   Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal
,
João Rocha
c   CICECO, Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
,
Artur M. S. Silva 
a   QOPNA, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal   Email: sguieu@ua.pt
,
Samuel Guieu∗
a   QOPNA, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal   Email: sguieu@ua.pt
c   CICECO, Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
› Author AffiliationsThanks are due to the University of Aveiro, FCT/MEC for financial support to the QOPNA research Unit (FCT UID/QUI/00062/2019), CICECO–Aveiro Institute of Materials (FCT Ref. UID/CTM/50011/2019), financed by national funds through FCT/MEC, and also to the Portuguese NMR Network. This work was also supported by the Integrated Programme of SR&TD ‘pAGE – Protein Aggregation Across the Lifespan’ (reference CENTRO-01-0145-FEDER-000003), co-funded by the Centro 2020 program, Portugal 2020, and the European Union, through the European Regional Development Fund.
Further Information

Publication History

Received: 07 January 2020

Accepted after revision: 31 January 2020

Publication Date:
13 February 2020 (online)

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Abstract

Pyrroles are widely found in natural products and play an important role in biological processes. Certain pyrrole derivatives are fluorescent and may be used as molecular probes or biomarkers in the diagnosis of diseases, such as Alzheimer’s or Parkinson’s. Herein is reported the synthesis of five new pyrrole derivatives bearing phenyl rings on positions 1, 2, and 4, with electron-donating groups at the periphery. The introduction of more or stronger electron-donating groups red-shifts and increases the efficiency of the fluorescence emission.

Key words

triphenylpyrroles - Nef reaction - Paal–Knorr reaction - fluorescence - crystal structure

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1690828.
  • Supporting Information
 

  • References and Notes

  • 1 Gholap SS. Eur. J. Med. Chem. 2016; 110: 13
    CrossrefPubMed
  • 2 Kaur R, Rani V, Abbot V, Kapoor Y, Konar D, Kumar K. J. Pharm. Chem. Chem. Sci. 2017; 1: 17
  • 3 Fleming CL, Ashton TD, Gaur V, McGee SL, Pfeffer FM. J. Med. Chem. 2014; 57: 1132
    CrossrefPubMed
  • 4 Idhayadhulla A, Surendra Kumar R, Jamal A, Nasser A. J. Mex. Chem. Soc. 2011; 55: 218
  • 5 Eakin AE, Green O, Hales N, Walkup GK, Bist S, Singh A, Mullen G, Bryant J, Embrey K, Gao N, Breeze A, Timms D, Andrews B, Uria-Nickelsen M, Demeritt J, Loch JT. III, Hull K, Blodgett A, Illingworth RN, Prince B, Boriack-Sjodin PA, Hauck S, MacPherson LJ, Ni H, Sherer B. Antimicrob. Agents Chemother. 2012; 56: 1240
    CrossrefPubMed
  • 6 Pagadala LR, Mukkara LD, Singireddi S, Singh A, Thummaluru VR, Jagarlamudi PS, Guttala RS, Perumal Y, Dharmarajan S, Upadhyayula SM, Ummanni R, Basireddy VS. R, Ravirala N. Eur. J. Med. Chem. 2014; 84: 118
    CrossrefPubMed
  • 7 Rane RA, Naphade SS, Bangalore PK, Palkar MB, Shaikh MS, Karpoormath R. Bioorg. Med. Chem. Lett. 2014; 24: 3079
    CrossrefPubMed
  • 8 He X.-Y, Lu L, Qiu J, Zou P, Yu F, Jiang X.-K, Li L, Jiang S, Liu S, Xie L. Bioorg. Med. Chem. 2013; 21: 7539
    CrossrefPubMed
  • 9 Lee H, Lee J, Lee S, Shin Y, Jung W, Kim J.-H, Park K, Kim K, Cho HS, Ro S, Lee S, Jeong SW, Choi T, Chung H.-H, Koh JS. Bioorg. Med. Chem. Lett. 2001; 11: 3069
    CrossrefPubMed
  • 10 Hall MJ, McDonnell SO, Killoran J, O’Shea DF. J. Org. Chem. 2005; 70: 5571
    CrossrefPubMed
  • 11 Kikuchi K, Hibi S, Yoshimura H, Tokuhara N, Tai K, Hida T, Yamauchi T, Nagai M. J. Med. Chem. 2000; 43: 409
    CrossrefPubMed
  • 12 Cardona F, Rocha J, Silva AM. S, Guieu S. Dyes Pigm. 2014; 111: 16
    Crossref
  • 13 Guieu S, Cardona F, Rocha J, Silva AM. S. New J. Chem. 2014; 38: 5411
    Crossref
  • 14 Hong Y, Lam JW. Y, Tang BZ. Chem. Soc. Rev. 2011; 40: 5361
    CrossrefPubMed
  • 15 Luo J, Xie Z, Lam JW. Y, Cheng L, Chen H, Qiu C, Kwok HS, Zhan X, Liu Y, Zhu D, Tang BZ. Chem. Commun. 2001; 1740
    PubMed
  • 16 Guieu S, Rocha J, Silva AM. S. Tetrahedron 2013; 69: 9329
    Crossref
  • 17 Vaz PA. A. M, Rocha J, Silva AM. S, Guieu S. New J. Chem. 2016; 40: 8198
    Crossref
  • 18 Guieu S. Quimica (Lisboa, Port.) 2018; 42: 97
  • 19 Guieu S, Cardona F, Rocha J, Silva AM. S. Chem. Eur. J. 2018; 24: 17262
    CrossrefPubMed
  • 20 Guieu S, Rocha J, Silva AM. S. Tetrahedron Lett. 2013; 54: 2870
    Crossref
  • 21 Guieu S, Pinto J, Silva VL. M, Rocha J, Silva AM. S. Eur. J. Org. Chem. 2015; 3423
  • 22 Würthner F, Kaiser TE, Saha-Möller CR. Angew. Chem. Int. Ed. 2011; 50: 3376
    CrossrefPubMed
  • 23 Kim E, Lee Y, Lee S, Park SB. Acc. Chem. Res. 2015; 48: 538
    CrossrefPubMed
  • 24 Feng X, Tong B, Shen J, Shi J, Han T, Chen L, Zhi J, Lu P, Ma Y, Dong Y. J. Phys. Chem. B 2010; 114: 16731
    CrossrefPubMed
  • 25 Lei Y, Liu Q, Dong L, Cai Z, Shi J, Zhi J, Tong B, Dong Y. Chem. Eur. J. 2018; 24: 14269
    CrossrefPubMed
  • 26 1,2,4-Triphenylpyrroles 4a–e; General Procedure The appropriate nitro ketone 2a–c (1 equiv) was dissolved in a mixture of MeOH (8 mL) and THF (12 mL) then KOH (1 equiv) was added. The mixture was stirred for 2 h. The solution, cooled in ice, was added dropwise to an ice-cold solution of concd H2SO4 (4 mL ) in MeOH (10 mL), and the mixture was stirred for ~1 h at rt. Half of the solvent was removed under reduced pressure and the mixture was poured in ice–water. The product was extracted with CH2Cl2 and the organic layer was dried (Na2SO4) and concentrated to dryness to give compound 3a–c, which was used in the following step without purification. The appropriate amine (1 equiv) was added to a solution of the acetal 3a–c (1 equiv) in MeOH (5 mL), and the resulting solution was stirred for 24 h at rt. During this time a precipitate formed. H2O was then added, and the product was extracted with CH2Cl2. The organic phase was dried (Na2SO4) and concentrated under reduced pressure. The crude product was purified by flash column chromatography (silica gel).
  • 27 1,2,4-Tris(4-methoxyphenyl)-1H-pyrrole (4c)Yellow–brown oil; yield: 23 mg (0.06 mmol, 11%). 1H NMR (300 MHz, CDCl3): δ = 7.50 (d, J = 8.8 Hz, 2 H), 7.15–7.08 (m, 4 H), 7.07 (d, J = 2.0 Hz, 1 H), 6.91 (d, J = 8.8 Hz, 2 H), 6.85 (d, J = 9.0 Hz, 2 H), 6.77 (d, J = 8.9 Hz, 2 H), 6.58 (d, J = 2.0 Hz, 1 H), 3.82 (s, 3 H), 3.81 (s, 3 H), 3.77 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 158.4, 158.3, 158.0, 134.7, 133.8, 129.7, 128.3, 127.1, 126.3, 125.6, 124.9, 119.8, 114.3, 114.3, 113.7, 107.3, 55.6, 55.4, 55.3. ESI(+)–HRMS: m/z [M + H]+ calcd for C25H24NO3: 386.1751; found: 386.1743 (–1.99 ppm).
  • 28 CCDC 1879235 contains the supplementary crystallographic data for compound 4b. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
  • 29 Allen FH, Kennard O, Watson DG, Brammer L, Orpen AG, Taylor R. J. Chem. Soc., Perkin Trans. 2 1987; S1