The Mannich reaction in the synthesis of N,S-containing heterocycles 3. Unexpected direction of the aminomethylation reaction of N-methylmorpholinium 1-amino-2,4-dicyano-4-ethoxycarbonyl-1,3-butadienethiolate. One stage cascade synthesis of new derivatives of pyrido[1,2-a][1,3,5]triazine

Abstract

Keywords: N-methylmorpholinium 1-amino-2,4-dicyano-4-ethoxycarbonyl-1,3-butadienethiolate, pyrido-[1,2-a][1,3,5]triazines, cascade heterocyclization, Mannich reaction, X-ray structural analysis.It is known from numerous literature data that the three-component Mannich cyclocondensation of a series of mercaptoazoles and -azines, formaldehyde, and primary amines serves as a convenient method of obtaining various heterocyclic systems annelated with the 1,3,5-thiadiazine ring [2][3][4][5][6][7][8][9][10][11]. Recently heterocyclization of a similar type was used successfully by us to obtain derivatives of pyrido-[2,1-b][1,3,5]thiadiazine [12,13]. Continuing investigations of polycomponent cascade reactions [14], we turned our attention to N-methylmorpholinium 1-amino-2,4-dicyano-4-ethoxycarbonyl-1,3-butadienethiolate (1) [15] as a promising subject for carrying out cascade heterocyclization under the conditions of the Mannich reaction. This diene is readily available and fairly stable. Even on boiling for 3 h it crystallizes out from _______ * For Part 2 see [1].

Synthesis of partially hydrogenated 1,3,5-thiadiazines by Mannich reaction

“…Chemistry of Heterocyclic Compounds 2015, 51 (2), [109][110][111][112][113][114][115][116][117][118][119][120][121][122][123][124][125][126][127] were observed, and the major products were dithiazines 20. Aniline and meta-substituted anilines under these conditions tended to form mixtures of compounds 13, 20, and 22 in various ratios (Scheme 5), with the fraction of dithiazines 20 increasing after longer reaction time; complete conversion of amine was achieved after 10 h. In general, it was noted 37а that 3,5-diaryl-substituted perhydro-1,3,5-thiadiazines were more stable than 3,5-dialkyl analogs, which readily disproportionated with the formation of dithiazines.…”

“…The reaction was sensitive both to the reactant ratio and reaction temperature, as well as the amount of catalyst used. Derivatives of perhydro-1,3,5-thiadiazine 38 could be Chemistry of Heterocyclic Compounds 2015, 51 (2), [109][110][111][112][113][114][115][116][117][118][119][120][121][122][123][124][125][126][127] obtained in up to 66% yield by heating (thio)urea with a mixture of CH 2 O and H 2 S (1 : 2 : 1 ratio) in the presence of n-BuONa (4 equiv) (Scheme 12). 43,84 It has been noted 43 that mostly macrocyclic condensation products were obtained under different conditions.…”

“…146,147 An unusual method for the construction of imidazo[1,5-c]-[1,3,5]thiadiazine system has been described. 148 (2), [109][110][111][112][113][114][115][116][117][118][119][120][121][122][123][124][125][126][127] Various S,N-binucleophilic compounds reacted with perfluoromethyleneimine 123; 151 the reaction can be considered as a special case of aminoalkylation. The reaction mechanism includes an attack by thiolate ion at the C=N bond of methyleneimine 123, elimination of F -ion with regenerating the С=N bond and subsequent N-aminoalkylation with cyclization.…”

“…Thus, tetrahydropyridine-2-thiolates 95 and 96 participated in Mannich reaction, forming the respective bispidines 97 and 98 (Scheme 38). [135][136][137] Chemistry of Heterocyclic Compounds 2015, 51 (2), [109][110][111][112][113][114][115][116][117][118][119][120][121][122][123][124][125][126][127] The Mannich reaction with thiolates 91 was studied in detail. The yields of products 19 were found to vary widely and substantially depended on the nature of primary amine and the structure of substituent at position 4 of the thiolate 91.…”

“…15 The most widely used compound of THTT series is 3,5-dimethyltetrahydro-1,3,5-thiadiazine-2-thione (5), known by the trade names Dazomet, Tiazone (in USSR), Basamid, Mylone, DMTT, and applied as highly potent soil fumigant, fungicide, herbicide, and powerful insecticide, as well as for the prevention of biofilm accumulation in paper industry. 16 Chemistry of Heterocyclic Compounds 2015, 51 (2), [109][110][111][112][113][114][115][116][117][118][119][120][121][122][123][124][125][126][127] Translated from Khimiya Geterotsiklicheskikh Soedinenii, 2015, 51 (2), [109][110][111][112][113][114][115][116][117][118][119][120][121][122][123][124][125][126][127] rapidly decomposes by forming MeNCS, MeNH 2 , СН 2 О, and Н 2 S, which provide for its fumigant activity. 18, 19 It has also been reported that thiazone 5 has ovicidal activity against...…”