Elsevier

Tetrahedron Letters

Volume 61, Issue 37, 10 September 2020, 152231
Tetrahedron Letters

Catalytic efficiency of β-cyclodextrin hydrate-chemoselective reaction of indoles with aldehydes in aqueous medium

https://doi.org/10.1016/j.tetlet.2020.152231Get rights and content

Highlights

  • Metal-free aqueous phase catalysis with high atom economy.

  • Tolerance of various sensitive moieties under eco-compatible condition.

  • Recyclable, stable and sustainable catalytic system.

  • Excellent chemoselectivity as well as gram scale applicability.

  • Generation of water as the sole and innocuous side-product.

Abstract

The catalytic efficiency of β-cyclodextrin hydrate has been investigated towards the eco-compatible synthesis of bis-(indolyl)methanes in aqueous medium by the chemoselective reaction of indoles with differently substituted aryl and alkyl aldehydes under mild reaction conditions. The catalytic attributes of β-cyclodextrin hydrate were also demonstrated through molecular docking and DFT studies. Reactions were slower in D2O than in H2O. Aryl and alkyl ketones remained unaffected under the present condition. Excellent chemoselectivity has been established through intermolecular as well as intramolecular competition experiments. Calculation of Green Chemistry Metrices showed high atom economy and small E-factor for the reaction.

Introduction

Cyclodextrins (CDs) are a family of macrocyclic oligosaccharides linked together by α-1,4 glucopyranose subunits and produced enzymatically from starch. β-Cyclodextrin (β-CD) consists of seven d-glucopyranose units forming a cyclic, hollow cone-shaped cavity and possessing hydrophilic exterior due to upper and lower rims decorated with hydroxyl groups as well as hydrophobic internal pocket that embrace substrates selectively [1] through inclusion complexes. But, β-Cyclodextrin hydrate (β-CDH) contains exchangeable hydrogen atoms [2] associated with protonic conductivity which is similar to that of hydrated proteins. The water molecules are present inside and outside of β-CD hydrate (β-CDH) provides an efficient path for the extended movement of protons which is also responsible for the protonic conductivity via a concerted and co-operative translocation of protons through the so-called flip-flop hydrogen bond [3]. The catalytic applications [4] of CDs for the synthesis of biologically important compounds have been reported. But surprisingly the catalytic attributes of β-cyclodextrin hydrate, which behaves differently from β-cyclodextrin, have not been explored much after the maiden report from our group [5].

Friedel-Crafts reaction is one of the cornerstone reactions for fundamental carbon–carbon (Csingle bondC) bond formation and construction of important classes of building blocks [6]. Bis-(indolyl)methanes (BIMs) are prominent and privileged structural motif in bioactive metabolites as well as compounds of both terrestrial and marine origin [7]. A broad range of biologically and pharmacologically active compounds, such as anticancer [8a], antitumor [8b], antifungal [8c], and HIV-1 integrase inhibitor [8d] also carry this structural unit. Therefore, various synthetic strategies such as solid acids [9a,9b], Lewis acids [9](c), [9](d), [9](e), [9](f), hetero-polyacids [9g], ionic liquids [9](h), [9](i), and many other transition metal-free protocols [9](j), [9](k), [9](l), [9](m), [9](n), [9](o), [9](p), [9](q) have been developed during the last few years. Several homogeneous and heterogeneous systems, such as Fe [10a], Cu [10b], Zn [10c], Ag [10d], Sc [10e], Mo [10f], Pd [10g], Nb [10h], Ni-Dy complex [10i], and Dy(OTf)3-ILs [10j], were also reported for the similar transformations. Even though these reported protocols are satisfactory, but they also suffer from certain disadvantages such as high temperature [[9], [9](a), [10](g)], long reaction time [9](p), [9](q), [10](c), [10](g), [10](i), [10](j), harsh reaction condition [10g], use of expensive metal catalysts [10](e), [10](f), [10](g), [10](h), [10](i), [10](j), limitation in gram scale production [9](a), [10](a), [10](d), [10](h), [10](i), [10](j), insufficient recovery of catalyst [10](b), [10](d), [10](e), [10](g), [10](i), lack of chemoselectivity [9](a), [9](h), [9](m), [9](n), [10](a), [10](d), [10](f), [10](j), [10](k), and involvement of organic solvents [9](e), [9](g), [10](b), [10](d), [10](e), [10](g), [10](k) having poor scope to recover and recycle. Therefore, an operationally simple, catalytically efficient, and eco-compatible protocol for the chemoselective synthesis of bis-(indolyl)methanes through the three component reaction [11] involving indoles [12] is of great demand from the standpoint of sustainability. The use of β-cyclodextrin hydrate (β- CD hydrate) as a mildly acidic, efficient and recyclable catalyst during an organic reaction in aqueous medium has been reported [5] for the first time from our group. In continuation of our investigations in this direction we report herein the synthesis of bis-(indolyl)methanes using β-CD hydrate as an eco-friendly catalyst through chemoselective Friedel-Crafts alkylation of substituted indoles with differently substituted aromatic and aliphatic aldehydes in aqueous medium where the assistive role of water molecules present inside the cavity of β-CD hydrate was established.

Section snippets

Results and discussion

We initiated our experiments by investigating the Friedel-Crafts alkylation reaction between 2-methylindole 1a (1 mmol) with 4-methoxybenzaldehyde 2a (0.5 mmol) in water at 60 °C in the presence of different catalysts with the variation of reaction time and catalyst loading to obtain the corresponding bis-(indolyl)methanes 3a (Table 1).

As shown in Table 1, the reaction did not occur at all in the absence of any catalyst (Entry 1), the unreacted substrates were isolated intact. The reaction was

Conclusion

Catalytic efficiency of β-cyclodextrin hydrate has been investigated towards the synthesis of bis-(indol-3-yl)-methanes through the Friedel-Crafts alkylation reaction of indoles with aryl, heteroaryl as well as alkyl aldehydes under mild reaction condition. This newly developed atom-economical protocol shows good chemoselectivity which has been substantiated through intermolecular as well as intramolecular competition experiments. Practical synthetic utility was also demonstrated by gram scale

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

Financial assistance from RUSA 2-Programme and UGC-CAS-II programme in Chemistry at Jadavpur University are gratefully acknowledged. S. N. thanks DST, INSPIRE, New Delhi for senior research fellowship. Thanks to Mr. N. Dutta of IACS and Mr. R. Biswas of JU for necessary assistance.

References (15)

  • M.G. Usha et al.

    J. Mol. Biol.

    (1989)
  • B. Madhav et al.

    Tetrahedron Lett.

    (2012)
    S. Noel et al.

    Catal. Today.

    (2014)
    F. Hapiot et al.

    Catal

    Sci. Technol.

    (2014)
    A. Kumar et al.

    Green Chem.

    (2015)
    V.V. Shinde et al.

    Catal. Commun.

    (2018)
  • A. Ghatak et al.

    Adv. Synth. Catal.

    (2016)
  • C. Grosso et al.

    Eur. J. Med. Chem.

    (2015)
    D. Li et al.

    Org. Lett.

    (2016)
    C.M. Bernt et al.

    Catal

    Sci. Technol.

    (2016)
    A. Srivastava et al.

    RSC Adv.

    (2016)
  • S.R. Mendes et al.

    Tetrahedron Lett.

    (2012)
    M. Esmaielpour et al.

    J. Chem. Sci.

    (2017)
    K.A. Shaikh et al.

    Res. J. Pharm. Biol. Chem. Sci.

    (2010)
    S.A. Sadaphal et al.

    Bulletin of the Catalysis Scoeity of India

    (2008)
    A. Swetha et al.

    Tetrahedron Lett.

    (2015)
    Z. Wu et al.

    Green Chem.

    (2019)
    K. Selvakumar et al.

    Synth. Commun.

    (2017)
    P.H. Tran et al.

    Asian, J. Org. Chem.

    (2018)
    M. Dabiri et al.

    J. Iran. Chem. Soc.

    (2007)
    R.G. Vaghei et al.

    J. Braz. Chem. Soc.

    (2010)
    K. Sujatha et al.

    Indian. J. Chem.

    (2009)
    A. Hasaninejad et al.V.D. Patil et al.

    Syn. Commun.

    (2011)
    G. Gao et al.

    ChemistrySelect.

    (2017)
    D.Z. Xu et al.

    Synthesis

    (2016)
    D. Sun et al.

    Chin. J. Chem.

    (2015)
    Y. Fu et al.

    RSC Adv.

    (2020)
  • Q. Wang et al.

    Polym. Chem.-UK

    (2013)
  • A. Anagnostopoulou et al.

    IEEE Trans. Electr. Insul.

    (1992)
There are more references available in the full text version of this article.

Cited by (10)

  • The maiden comprehensive report on emerging trend towards metal free synthesis of biologically potent 2H-Chromenes

    2022, Tetrahedron
    Citation Excerpt :

    In recent years water has emerged as a versatile solvent for organic chemistry as it is not only inexpensive but also environmentally benign [44–48]. Cyclic oligosaccharides like cyclodextrins and crown ethers having hydrophobic cavities are well established as supramolecular catalysts in water as they can form reversible host-guest complexes [49]. An eco-compatible aqueous phase supramolecular catalysis by β-cyclodextrin hydrate was accomplished by Ghatak et al. in 2016.

  • An eco-friendly, one pot synthesis of tri-substituted imidazoles in aqueous medium catalyzed by RGO supported Au nano-catalyst and computational studies

    2021, Journal of Molecular Structure
    Citation Excerpt :

    The geometrical structure of the singlet ground state (S0) were optimized using the density functional theory (DFT) method at the RB3LYP levels of theory [33] using 6–311 g basis set for C, H, O atoms in solution phase. The absorption spectral properties of the compound 5 based on the optimized ground state geometry structure was computed using the time dependent density functional theory (TDDFT) [34] approach in dichloromethane solution associated with the conductor-like polarizable continuum model (CPCM) [35]. All the calculations were performed using the Gaussian 09 W software package [36].

View all citing articles on Scopus
View full text