Download PDF
Synlett
DOI: 10.1055/a-2604-4702
letter

Oxone-Mediated Mild Removal of an Azine Protecting/Directing Group for Applications in Organic Synthesis

Gokul Ganesan‡
a   National Center for Nanosciences and Nanotechnology, University of Mumbai, Vidyanagari, Mumbai 400098, Maharashtra, India
c   Department of Chemistry, Jai Hind College Autonomous, ‘A’ Road, Churchgate, Mumbai 400020, Maharashtra, India
,
Pownthurai Balasubramaniam‡
a   National Center for Nanosciences and Nanotechnology, University of Mumbai, Vidyanagari, Mumbai 400098, Maharashtra, India
,
Mukeshkumar Yadav‡
a   National Center for Nanosciences and Nanotechnology, University of Mumbai, Vidyanagari, Mumbai 400098, Maharashtra, India
,
Hardik Janwadkar
b   Department of Chemistry, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai 400019, India
,
Abhijit Papalkar
d   Department of Chemistry, Fergusson College, F.C. Road, Pune 411004, Maharashtra, India
,
Atul Chaskar∗
b   Department of Chemistry, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai 400019, India
› Author Affiliations
› Further Information
   Permissions and Reprints All articles of this category


Abstract

Azine derivatives of carbonyl compounds are used as protecting groups and have recently been utilized as directing groups in C–H activation. The stability of the azine functional group limits its application in areas where its subsequent removal is desirable. We herein report a mild and efficient method for removal of an azine group using Oxone as a green oxidant in the presence of an acetone/water solvent system. Carbonyl regeneration occurs in high yields from a range of aldazine and ketazine derivatives. A gram-scale synthesis and removal of the azine directing group from an ortho-functionalized azine are performed to extend the application of this methodology.

Key words

azines - oxidative deprotection - Oxone - directing groups - carbonyl compounds

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2604-4702.
  • Supporting Information


Publication History

Received: 02 February 2025

Accepted after revision: 08 May 2025

Accepted Manuscript online:
08 May 2025

Article published online:
03 July 2025

© 2025. Thieme. All rights reserved

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References and Notes

  • 1 Dickens TK, Warren SG. Chemistry of the Carbonyl Group: A Step-by-Step Approach to Understanding Organic Reaction Mechanisms. John Wiley & Sons; Hoboken: 2018
    Search in Google Scholar
  • 2 Safari J, Gandomi-Ravandi S. RSC Adv. 2014; 4: 46224
    Search in Google Scholar
  • 3 Chourasiya SS, Kathuria D, Wani AA, Bharatam PV. Org. Biomol. Chem. 2019; 17: 8486
    Search in Google Scholar
  • 4 Dascalu AE, Halgreen L, Torres-Huerta A, Valkenier H. Chem. Commun. 2022; 58: 11103
    Search in Google Scholar
  • 5 Shirini F, Mamaghani M, Rahmanzadeh A. ARKIVOC 2007; (i): 34
    Search in Google Scholar
  • 6 Dekova BY, Evers MJ, Christiaens LR, Guillaume MR. Bull. Soc. Chim. Belg. 1987; 96: 219
    Search in Google Scholar
  • 7 Mohammadpoor altork I, Pouranshirvani Sh. Synth. Commun. 1996; 26: 1
    Search in Google Scholar
  • 8 Paredes R, Bastos H, Montoya R, Chavez AL, Dolbier WR, Burkholder CR. Tetrahedron 1988; 44: 6821
    Search in Google Scholar
  • 9 Zolfigol MA, Poor-Baltork IM, Mirjalili BF, Shirini F, Salehzadeh S, Keypour H, Ghorbani-Choghamarani A, Zebarjadian MH, Mohammadi K, Hazar A. Phosphorus, Sulfur Silicon Relat. Elem. 2003; 178: 2735
    Search in Google Scholar
  • 10 Nanjundaswamy HM, Pasha MA. Synth. Commun. 2006; 36: 3161
    Search in Google Scholar
  • 11 Shirini F, Zolfigol MA, Safari A, Mohammadpoor-Baltork I, Mirjalili BF. Tetrahedron Lett. 2003; 44: 7463
    Search in Google Scholar
  • 12 Giurg M, Młochowski J. Synth. Commun. 1999; 29: 4307
    Search in Google Scholar
  • 13 Carmeli M, Rozen S. Tetrahedron Lett. 2006; 47: 763
    Search in Google Scholar
  • 14 Habibi D, Zolfigol MA, Faraji AR, Rahmani P. Monatsh. Chem. 2012; 143: 809
    Search in Google Scholar
  • 15 Mohammadpoor-Baltork I, Khodaei MM, Hajipour AR, Aslani E. Monatsh. Chem. 2003; 134: 539
    Search in Google Scholar
  • 16 Kumar H, Kaur B, Kumar B. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1991; 30: 869
    Search in Google Scholar
  • 17 Lim YG, Koo BT. Tetrahedron Lett. 2005; 46: 385
    Search in Google Scholar
  • 18 Yu Y, Kuai C, Chauvin R, Tian N, Ma S, Cui X. J. Org. Chem. 2017; 82: 8611
    Search in Google Scholar
  • 19 Wen J, Wu A, Wang M, Zhu J. J. Org. Chem. 2015; 80: 10457
    Search in Google Scholar
  • 20 Vu HM, Yong JY, Chen FW, Li XQ, Shi GQ. J. Org. Chem. 2020; 85: 4963
    Search in Google Scholar
  • 21 Mishra NK, Oh Y, Jeon M, Han S, Sharma S, Han SH, Um SH, Kim IS. Eur. J. Org. Chem. 2016; 4976
  • 22 Ban T, Vu HM, Zhang J, Yong JY, Liu Q, Li XQ. J. Org. Chem. 2022; 87: 5543
    Search in Google Scholar
  • 23 Wen J, Wu A, Miao Y, Zhu J. Tetrahedron Lett. 2015; 56: 5512
    Search in Google Scholar
  • 24 Kianmehr E, Seifinoferest B, Afaridoun H. Eur. J. Org. Chem. 2020; 4925
  • 25 Han W, Zhang G, Li G, Huang H. Org. Lett. 2014; 16: 3532
    Search in Google Scholar
  • 26 Deshmukh DS, Yadav PA, Bhanage BM. Org. Biomol. Chem. 2019; 17: 3489
    Search in Google Scholar
  • 27 Dönnecke D, Wunderle J, Imhof W. J. Organomet. Chem. 2004; 689: 585
    Search in Google Scholar
  • 28 Hussain H, Green IR, Ahmed I. Chem. Rev. 2013; 113: 3329
    Search in Google Scholar
  • 29 Azine Directing Group Removal; General Procedure A round-bottomed flask was charged with Oxone (1.74 g, 6 equiv) in H2O (7.5 mL). A solution of the corresponding azine-protected carbonyl substrate (0.95 mmol) in acetone (7.5 mL) was added dropwise to the flask and the resulting mixture was allowed to stir at room temperature until completion of reaction (monitored by TLC). The reaction was quenched by adding H2O (20 mL) and extracted using ethyl acetate. The organic layer was dried over sodium sulfate and evaporated under reduced pressure. The obtained product was dried under vacuum.
  • 30 3-(Trifluoromethyl)benzaldehyde (2i) Time required for conversion: 40 min. 1H NMR (400 MHz, CDCl3): δ = 10.00 (d, J = 1.0 Hz, 1 H), 8.06 (s, 1 H), 8.01 (d, J = 7.8 Hz, 1 H), 7.80 (d, J = 7.9 Hz, 1 H), 7.62 (t, J = 7.8 Hz, 1 H). 13C NMR (101 MHz, CDCl3): δ = 190.82, 136.82, 132.74, 130.69, 129.79, 126.23, 124.88, 122.14. MS (ESI): m/z = 174.03.
  • 31 3,4,5-Trimethoxyacetophenone (2o) Time required for conversion: 90 min. 1H NMR (400 MHz, DMSO-d6): δ = 7.24 (s, 2 H), 3.85 (s, 6 H), 3.73 (s, 3 H), 2.58 (s, 3 H). 13C NMR (101 MHz, DMSO-d6): δ = 197.04, 141.93, 132.32, 105.81, 60.24, 56.10, 26.69. MS (ESI): m/z = 210.07.
  • 32 Bigdeli MA, Nikje MM. A, Heravi MM. Phosphorus, Sulfur Silicon Relat. Elem. 2010; 177: 2309
    Search in Google Scholar