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

• Published in: Chemistry of heterocyclic compounds (New York, N.Y. 1965) N.Y. 1965), 2016-02, Vol.52 (2), p.116-127
• Main Authors: Dotsenko, Victor V., Frolov, Konstantin А., Krivokolysko, Sergey G., Chigorina, Elena A., Pekhtereva, Tatyana M., Suykov, Sergey Yu, Papayanina, Elena S., Dmitrienko, Artem О., Bushmarinov, Ivan S.
• Format: Article
• Language: English
• Subjects: Aromatic amines; Bisphenol-A; Chemistry; Chemistry and Materials Science; Formaldehyde; Organic Chemistry; Pharmacy
• ISSN: 0009-3122; 1573-8353
• DOI: 10.1007/s10593-016-1843-5

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 RCH 2 NH 2 and excess formalin (2 equiv and more) produced 7-RCH 2 -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-2 H ,6 H -pyrido[2,1- b ][1,3,5]thiadiazine-7,9-dicarbonitriles. The treatment of thiolates with 1 equiv of НСНО and 1 equiv of RCH 2 NH 2 led to 7-RCH 2 -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.