The study of the three-component interaction between 1-ethyl-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide, heterylcarbaldehydes and active methylene nitriles

D. A. Lega, V. P. Chernykh, L. A. Shemchuk


Some peculiarities of the three-component interaction of 1-ethyl-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide with active methylene nitriles and heterylcarbaldehydes have been described in this article. It has been found that if malononitrile is used, the products of the three-component reaction are 2-amino-4-heteryl-3-cyano-6-ethyl-4,6-dihydropyrano[3,2-c][2,1]benzothiazine 5,5-dioxides irrespective of the heteryl fragment nature in the initial aldehyde. When using ethyl cyanoacetate (as the active methylene nitrile) in the three-component interaction instead malononitrile the reaction lost its selectivity. In this case, depending on the heterylcarbaldehyde, three different types of products were obtained, namely 2-amino-3-alkoxycarbonyl-4-heteryl-4H-pyranes (for pyridine-3-, pyridine-4-carbaldehydes and furan-2-carbaldehyde), thriethylammonium salt of bis(1-ethyl-1H-2,1-benzothiazin-2,2- dioxo-4-ol-3-yl)(2-thienyl)methane (for thiophen-2-carbaldehyde) or ethyl 2-cyano-3-(1H-indol-3-yl)acrylate (for indol-3-carbaldehyde). Formation of a stable triethylammonium salts was considered as the process competitive with formation of 2-amino-4H-pyranes. It has allowes to propose the modiŸed mechanism of 2-amino-4H-pyranes formation. This mechanism includes the stage of forming triethylammonium salts of bis-adducts. According to this mechanism 2-amino-3-ethoxycarbonyl-4-(2-thienyl)-4H-pyrane without any impurity of bis-adduct could be selectively obtained using the three-component interaction. Triethylammonium salts of bis-adducts were obtained by direct interaction of 1-ethyl-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide with heterylcarbaldehydes in the presence of equimolar amounts of triethylamine. It has been shown that the three-component interaction of  1-ethyl-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide with active methylene nitriles and heterylcarbaldehydes is a more  effective tool in order to obtain condensed 2-amino-4-heteryl-4H-pyranes compared to the stepwise approach.


2,1-benzothiazine 2,2-dioxide; heterylcarbaldehydes; active methylene nitriles; 4H-pyranes; three- component reaction; triethylammonium salts

Full Text:



Hicks J. L., Roark W. H. WO2004014388A1, 2004.

Hu Q.-Y., Ksander G. M. WO2008076860A1, 2008.

Nie H., Widdowson K. L. WO 9834929, 1998.

Catsoulacos P., Camoutsis C. J. Heterocycl. Chem., 1979, Vol. 23, No.8, pp.1503-1524.

Muegge I. Medicinal Research Reviews, 2003, Vol. 23, No.3, pp.302-321.

Supuran C. T., Casini A., Scozzafava A. Medicinal Research Reviews, 2003, Vol. 23, No.5, pp.535-558.

Hanson P. R., Probst D. A., Robinson R. E., Yau M. Tetrahedron Lett., 1999, Vol. 40, No.26, pp.4761-4764.

Moree W. J., van der Marel G. A., Liskamp R. M. J. Tetrahedron Lett., 1991, Vol. 32, No.3, pp.409-412.

Harmata M., Calkins N. L., Baughman R. G., Barnes C. L. J. Org. Chem., 2006, Vol. 71, No.9, pp.3650-3652.

Misu Y., Togo H. Org. Biomol. Chem., 2003, Vol. 1, No.8, pp.1342-1346.

Fairhurst J., Gallagher P. WO 2001087881, 2001.

Li W., Marlowe C. K., Scarborough R. M. WO 2001072725, 2001.

Yoakim C., O’Meara J., Simoneau B., Ogilie W. W., Deziel R. WO 2004026875, 2004.

Pieroni M., Sabatini S., Massari S., Kaatz G. W., Cecchetti V., Tabarrini O. Med. Chem. Commun., 2012, Vol. 3, No.9, pp.1092-1097.

Ukrainets I. V., Petrushova L. A., Dzyubenko S. P., Liu Y. Chem. Heterocycl. Compd. (N. Y., NY, U. S.), 2014, Vol. 50, No.4, pp.564-572.

Loev B., Kormendy M. F., Snader K. M. J. Org. Chem., 1966, Vol. 31, No.11, pp.3531-3534.

Lombardino J. G. J. Heterocycl. Chem., 1972, Vol. 9, No.2, pp.315-317.

Coppo F. T., Fawzi M. M. J. Heterocycl. Chem., 1998, Vol. 35, No.4, pp.983-987.

Shemchuk L. A., Lega D. A., Redkin R. G., Chernykh V. P., Shishkin O. V., Shishkina S. V. Tetrahedron, 2014, Vol. 70, No.44, pp.8348-8353.

Amirnejad M., Naimi-Jamal M. R., Tourani H., Ghafuri H. Monatsh. Chem., 2013, Vol. 144, No.8, pp.1219-1225.

Brahmachari G., Banerjee B. ACS Sustainable Chemistry & Engineering, 2013, Vol. 2, No.3, pp.411-422.

Shaterian H. R., Arman M., Rigi F. J. Mol. Liq., 2011, Vol. 158, No.2, pp.145-150.

Patel V. K., Sen D. J., Patel C. N. J. Chem. Pharm. Res., 2010, Vol. 2, No.2, pp.50-56.

Zanwar M. R., Raihan M. J., Gawande S. D., Kavala V., Janreddy D., Kuo C.-W., Ambre R., Yao C.-F. J. Org. Chem., 2012, Vol. 77, No.15, pp.6495-6504.

Redkin R. G., Shemchuk L. A., Chernykh V. P., Shishkin O. V., Shishkina S. V. Tetrahedron, 2007, Vol. 63, No.46, p.11444-11450.

GOST Style Citations

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Abbreviated key title: Ž. org. farm. hìm.

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)