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Aminomethylation of morpholinium and N-methylmorpholinium 3,5-dicyano-4,4-dimethyl-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolates

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Chemistry of Heterocyclic Compounds Aims and scope

The structure of reaction products obtained from 3,5-dicyano-4,4-dimethyl-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolates, primary amines, and formaldehyde substantially depends on the nature of counter-ion (morpholinium or N-methylmorpholinium), as well as on the primary amine structure and the ratio of reactants. Aminomethylation of these thiolates with highly nucleophilic amines RCH2NH2 and excess formalin (2 equiv and more) produced 7-RCH2-9,9-dimethyl-2-oxo-4-thioxo-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarbonitrile salts, which gave the respective bispidines upon acidification. Performing this reaction with aromatic amines in the case of N-methylmorpholinium 3,5-dicyano-4,4-dimethyl-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolate led to analogous bispidines, while the morpholinium salt gave 3-aryl-8,8-dimethyl-7-[(morpholin-4-yl)methyl]-6-oxo-3,4,7,8-tetrahydro-2H,6H-pyrido[2,1-b][1,3,5]thiadiazine-7,9-dicarbonitriles. The treatment of thiolates with 1 equiv of НСНО and 1 equiv of RCH2NH2 led to 7-RCH2-4-amino-9,9-dimethyl-2-oxo-6-thioxo-3,7-diazabicyclo[3.3.1]non-3-ene-1-carbonitriles. The molecular and crystal structures of key compounds were studied in detail by X-ray structural analysis.

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Notes

  1. This assumption was confirmed during the private communication with the authors of works:1 , 2 instead of 37% formalin, HCHO solution with lower concentration with a density of d ~ 1.01 g/ml, obtained by separation of the paraformaldehyde from formalin stored in the cold, was used.

  2. Here and further an asterix in 13С APT and DEPT-135 NMR spectra indicates opposite phase signals. The assignment of signals was based on 1H–13C HMBC spectra (see the Supplementary information).

  3. Error in the calculation was made in the paper:1 40 mmol of 37% formalin (d 1.1 g / ml) correspond to the volume of 3.0 ml instead of 3.6 ml as the authors indicated. However, in general it does not change the picture as a reproduction of the method with specified amount, as well as with a greater excess of HCHO, leads to the same result.

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The authors I. S. Bushmarinov and A. O. Dmitrienko would like to acknowledge the financial support received from the Russian Science Foundation (grant 14-13-00884).

The authors express their gratitude to the late professor Dr. Chem. Oleg V. Shishkin (29.07.1966–17.07.2014) and his colleagues (Scientific-Technological Complex ''Institute of Single Crystals'', Kharkiv, Ukraine) for X-ray structural studies of compound 4а.

The authors also appreciate the assistance from Candidate of Chemical Sciences A. V. Mazepa (A. V. Bogatsky Physical Chemistry Institute, Odessa, Ukraine) for the recording of mass spectra (EI, FAB), as well as A. Yu. Kostyuk (Scientific Production Company Mikrokhim Ltd., Rubezhnoye, Ukraine) for recording the IR spectra.

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Authors and Affiliations

  1. Kuban State University, 149 Stavropol’skaya St, Krasnodar, 350040, Russia

    Victor V. Dotsenko, Konstantin А. Frolov & Sergey G. Krivokolysko

  2. Federal State Unitary Enterprise “ IREA”, Bogorodsky val 3, 107076, Moscow, Russia

    Elena A. Chigorina

  3. L. M. Litvinenko Institute of Physical-Organic Chemistry and Coal Chemistry, 70 R. Luxemburg St, Donetsk, 83114, Ukraine

    Tatyana M. Pekhtereva & Sergey Yu. Suykov

  4. Institute of Organic Chemistry II, University of Erlangen-Nürnberg, 42 Henkestr, Erlangen, 91054, Germany

    Elena S. Papayanina

  5. A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilova St, Moscow, 117813, Russia

    Artem О. Dmitrienko & Ivan S. Bushmarinov

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  1. Victor V. Dotsenko
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  2. Konstantin А. Frolov
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  9. Ivan S. Bushmarinov
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Correspondence to Victor V. Dotsenko.

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Translated from Khimiya Geterotsiklicheskikh Soedinenii, 2016, 52(2), 116–127

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Dotsenko, V.V., Frolov, K.А., Krivokolysko, S.G. et al. Aminomethylation of morpholinium and N-methylmorpholinium 3,5-dicyano-4,4-dimethyl-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolates. Chem Heterocycl Comp 52, 116–127 (2016). https://doi.org/10.1007/s10593-016-1843-5

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