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Synlett 2016; 27(16): 2384-2390
DOI: 10.1055/s-0035-1562614
letter
© Georg Thieme Verlag Stuttgart · New York

A Catalyst-Free One-Pot Protocol for the Construction of Substituted Isoindolinones under Sustainable Conditions

Koneni V. Sashidhara*
a   Medicinal and Process Chemistry Division, CSIR - Central Drug Research Institute, Lucknow, 226 031, India   eMail: sashidhar123@gmail.com   eMail: kv_sashidhara@cdri.res.in
,
L. Ravithej Singh
a   Medicinal and Process Chemistry Division, CSIR - Central Drug Research Institute, Lucknow, 226 031, India   eMail: sashidhar123@gmail.com   eMail: kv_sashidhara@cdri.res.in
,
Gopala Reddy Palnati
a   Medicinal and Process Chemistry Division, CSIR - Central Drug Research Institute, Lucknow, 226 031, India   eMail: sashidhar123@gmail.com   eMail: kv_sashidhara@cdri.res.in
,
Srinivasa Rao Avula
a   Medicinal and Process Chemistry Division, CSIR - Central Drug Research Institute, Lucknow, 226 031, India   eMail: sashidhar123@gmail.com   eMail: kv_sashidhara@cdri.res.in
,
Ruchir Kant
b   Molecular and Structural Biology Division, CSIR - Central Drug Research Institute, Lucknow, 226 031, India
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 17. Mai 2016

Accepted after revision: 22. Juli 2016

Publikationsdatum:
08. August 2016 (online)

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Abstract

An operationally simple, one-pot, catalyst-free method was developed for the synthesis of pharmaceutically important substituted isoindolinones by a three-component reaction of 2-formylbenzoic acid, a primary amine, and a 1,3-dione in ethanol under dielectric heating.

Key words

isoindolinones - medicinal chemistry - multicomponent reaction - formylbenzoic acid - amines - diones

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1562614.
  • Supporting Information
 

  • References and Notes

  • 3 Yoo KD, Park ES, Lim Y, Kang SI, Yoo SH, Won HH, Kim YH, Yoo ID, Yoo HS, Hong JT, Yun YP. J. Pharm. Sci. 2012; 118: 171
    CrossrefSuche in Google Scholar
  • 4 Selvakumar J, Ramanathan CR. Org. Biomol. Chem. 2011; 9: 7643
    CrossrefPubMedSuche in Google Scholar
  • 5 Takahashi I, Kawakami T, Hirano E, Yokota H, Kitajima H. Synlett 1996; 353
    Thieme Connect
    • 6a Badros AZ. N. Engl. J. Med. 2012; 366: 1836
      CrossrefSuche in Google Scholar
    • 6b McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, Giralt S, Stadtmauer EA, Weisdorf DJ, Vij R, Moreb JS, Callander NS, Van Besien K, Gentile T, Isola L, Maziarz RT, Gabriel DA, Bashey A, Landau H, Martin T, Qazilbash MH, Levitan D, McClune B, Schlossman R, Hars V, Postiglione J, Jiang C, Bennett E, Barry S, Bressler L, Kelly M, Seiler M, Rosenbaum C, Hari P, Pasquini MC, Horowitz MM, Shea TC, Devine SM, Anderson KC, Linker C. N. Engl. J. Med. 2012; 366: 1770
      CrossrefSuche in Google Scholar
  • 7 Shin H.-S, Oh J.-A. J. Sep. Sci. 2012; 35: 541
    CrossrefSuche in Google Scholar
  • 9 Beak P, Kerrick ST, Gallagher DJ. J. Am. Chem. Soc. 1993; 115: 10628
    CrossrefSuche in Google Scholar
  • 10 Tyagi V, Khan S, Chauhan PM. S. Synlett 2013; 24: 645
    Thieme ConnectSuche in Google Scholar
  • 14 Kappe CO, Dallinger D. Nat. Rev. Drug Discov. 2006; 5: 51
    CrossrefSuche in Google Scholar
  • 19 3-(2-Hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-2-(4-tolyl)isoindolin-1-one (10a); Typical Procedure A mixture of 2-formylbenzoic acid (7; 1.0 mmol), p-toluidine (8a; 1.0 mmol), and dimedone (9b; 1.0 mmol) in EtOH (1 mL) was stirred for 1 min and then subjected to microwave irradiation at 90 °C for 15 min. When the reaction was complete, the mixture was filtered and the product was dried to give a white solid; yield: 0.333 g (0.92 mmol, 92%); mp 264–266 °C; IR (KBr): 3404, 2922, 1622, 1206, 1095 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.72 (d, J = 7.4 Hz, 1 H), 7.44 (t, J = 7.4 Hz, 1 H), 7.35 (t, J = 7.4 Hz, 1 H), 7.28 (d, J = 7.8 Hz, 2 H), 7.21 (d, J = 7.4 Hz, 1 H), 7.04 (d, J = 7.9 Hz, 2 H), 6.43 (s, 1 H), 2.27 (d, J = 16.6 Hz, 1 H), 2.20 (s, 3 H), 2.09 (d, J = 16.6 Hz, 1 H), 2.01 (d, J = 16.8 Hz, 1 H), 1.84 (d, J = 16.9 Hz, 1 H), 0.89 (s, 3 H), 0.49 (s, 3 H). 13C NMR (75 MHz, pyridine-d 5): δ = 190.2, 183.6, 169.4, 148.0, 138.2, 135.4, 134.9, 133.1, 130.6, 129.0, 124.4, 123.8, 123.6, 111.1, 57.6, 49.2, 47.9, 33.2, 29.7, 28.6, 22.0. HRMS (ESI): m/z [M + H]+ calcd for C23H24NO3: 362.1751; found: 362.1730.
  • 20 CCDC 1460875 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
  • 21 Isoindolo[1,2-b][1,3]benzothiazol-11(4bH)-one (11); Typical Procedure A mixture of 2-formylbenzoic acid (7, 1.0 mmol) and 2-aminobenzenethiol (1.0 mmol) in EtOH (1 mL) was stirred for 1 min then subjected to microwave irradiation at 90 °C for 15 min. When the reaction was complete (TLC), the excess EtOH was evaporated under reduced pressure and the residue was purified by column chromatography [silica gel, MeOH–CH2Cl2 (2:98)] to give a white solid; yield: 0.200 g (0.84 mmol, 84%); mp 173–175 °C. IR (KBr): 3404, 2922, 1622, 1206, 1095 cm–1; 1H NMR (300 MHz, CDCl3): δ = 7.94 (d, J = 7.3 Hz, 1 H), 7.68–7.63 (m, 2 H), 7.60–7.53 (m, 2 H), 7.22–7.16 (m, 2 H), 7.11–7.06 (m, 1 H), 6.99 (s, 1 H). 13C NMR (75 MHz, CDCl3): δ = 168.5, 143.1, 136.6, 135.9, 133.2, 132.7, 129.9, 125.9, 125.9, 125.2, 123.6, 123.1, 118.5, 69.2. HRMS (ESI): m/z [M + H]+ calcd for C14H10NOS: 240.0478; found: 240.0474.