Ninhydrin reaction with phenylethylamine: unavoidable by-products

Abstract

Ninhydrin and phenylethylamine reacted to form a complex mixture from which four products were isolated: a benzo-fused spiroheterocyclic and a pyrrole product resulting from tricomponent condensation between ninhydrin, phenylethylamine and phenylacetaldehyde produced in situ, a 2-amino-1,3-indandione dimerisation-dehydrogenation product and a Schiff base. This article analyses these compounds’ structure and proposes reaction mechanisms contributing to knowledge regarding ninhydrin and phenylethylamine chemical reactivity.

Graphic abstract

Ninhydrin and phenylethylamine reacted to form a benzo-fused spiroheterocyclic, a pyrrole, a 2-amino-1,3-indandione dimerisation-dehydrogenation product and a Schiff base.

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References

  1. 1.

    Ziarani G M, Lashgari N, Azimian F, Kruger H G and Gholamzadeha P 2015 Ninhydrin in synthesis of heterocyclic compounds ARKIVOC. 6 1

    Google Scholar 

  2. 2.

    McCaldin D 1960 The chemistry of ninhydrin Chem. Rev. 60 39

    CAS  Article  Google Scholar 

  3. 3.

    Omar M A, Hammad M A, Nagy D M and Aly A A 2015 Development of spectrofluorimetric method for determination of certain aminoglycoside drugs in dosage forms and human plasma through condensation with ninhydrin and phenyl acetaldehyde Spectrochim. Acta Part A 136 1760

    CAS  Article  Google Scholar 

  4. 4.

    Weigele M, Blount J F, Tengi J P, Czajkowski R C and Leimgruber W 1972 Fluorogenic ninhydrin reaction. Structure of the fluorescent principle J. Am. Chem. Soc. 94 4052

    Article  Google Scholar 

  5. 5.

    Quevedo-Acosta Y, Pérez-Redondo A and Quevedo R 2015 An unexpected route for the synthesis of a new spiroheterocyclic system from ninhydrin Tetrahedron Lett. 56 5309

    CAS  Google Scholar 

  6. 6.

    Sarkar S, Osisioma O, Karney W, Abe M and Gudmundsdottir D 2016 Using molecular architecture to control the reactivity of a triplet vinylnitrene J. Am. Chem. Soc. 138 14905

    CAS  Article  Google Scholar 

  7. 7.

    Wittmann H, Müller A and Ziegler E 1970 New reagents for the detection of amino acids by paper chromatography, VI Concerning the “Ninhydrin reaction” Monatsh. für Chem. 101 1388

    CAS  Article  Google Scholar 

  8. 8.

    Song H N, Lee H J, Kim H R, Ryu E K and Kim J N 1999 Friedel–Crafts type reactions of some activated cyclic ketones with phenol derivatives Synth. Commun. 29 3303

    CAS  Article  Google Scholar 

  9. 9.

    Araya-Maturana R, Pessoa-Mahana H and Weiss-López B 2008 Very long-range correlations (nJC,H n > 3) in HMBC spectra Nat. Prod. Commun. 3 445

    CAS  Google Scholar 

  10. 10.

    Williamson D S, Smith R A, Nagel D L and Cohen S M 1989 Phase-sensitive heteronuclear multiple-bond correlation in the presence of modest homonuclear coupling Application to distamycin A J. Magn. Reson. 82 605

    CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank the Universidad Nacional de Colombia (DIB Research Project No. 37398) for providing financial support. On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Correspondence to Rodolfo Quevedo.

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Gonzalez-Oñate, A., Quevedo, R. Ninhydrin reaction with phenylethylamine: unavoidable by-products. J Chem Sci 132, 49 (2020). https://doi.org/10.1007/s12039-020-1751-1

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Keywords

  • Ninhydrin
  • phenylethylamine
  • phenylacetaldehyde
  • Schiff base