Heterocyclisierungen, XII. Synthese von Benzimidazo[1,2‐a]‐s‐triazinen

Abstract

zP)-S-MazinesThe base-catalyzed reaction of 2-guanidinobenzimidazole (7) with benzoyl and ethoxycarbonyl isothiocyanate (2a, b) leads via the formation of instable intermediates 8, 9, 11 and elimination of HSCN in the side chain to the hitherto unknown 2-aminobenzimidazo[l,2-a]-s-triazines 10 and 13, resp. The latter is also formed by the reaction of 7 with benzoyl or ethoxycarbonyl isocyanate (2c, d) via the adducts 12, 14 and formal elimination of benzamide or urethane, resp. Under similar conditions, 2-aminobenzimidazole (15) reacts via the adducts 16,18 to give the 0x0-or dioxo-benzimidazo-triazines 17, 19.2-Aminoazole 1 kondensieren mit knzoyl-bzw. Athoxycarbonyliso(thio)cyanaten 2 uber die Harnstoffderivate 3 zu Azolo-s-triazinen mit Briickenkopf-Stickstoff 4 bzw. 5 (Gleichung 1)2). Bei den elektronenarmen Verbindungen Aminotriazol, -tetrazol und -benzimidazol jedoch wird die Heterocyclisierung mit zweidhnigen Isothiocyanaten durch HSCN-Eliminierung verdrangt, wobei die Benzamino-bzw.(Athoxycarbony1arnino)azole 6 gebildet werden 2). Der Mechanismus der HSCNEliminierung wurde als Umacylierung geklart (Reaktion 2)3).Im folgenden wurde anstelle von Aminoazolen 2-Guanidinobenzimidazol (7) mit Benzoyl-und khoxycarbonylisothiocyanat (2a, b) urngesetzt : Durch die Verllngerung der Seitenkette sollte fur die prirnar zu erwartenden Thiocarbarnoylguanidine dieser Reihe selbst nach Abspaltung von HSCN noch die Moglichkeit eines Sechsringschlusses zu einem tricyclischen Bruckenkopfstickstoff-System gegeben sein.

Synthesis of 2‐amino‐s‐triazino[1,2‐a]benzimidazoles as potential antifolates from 2‐guanidino‐ and 2‐guanidino‐5‐methylbenzimidazoles

“…The satisfied purity of the samples was achieved by careful washing with ethanol (acetone) that confirmed by nmr spectral data and elemental analyses. General Procedure for Preparation of 2-Benzimidazolylguanidines (5).…”

“…mp >360° [5,8,10], mp > 300° [11]); ir (potassium bromide): NH 3415, NH 3219, NH 3123, 2997, 2886, 2800, C=O 1717, NH 2 1616, 1601, 1526, 1457, 1405, 736 cm -1 ; 1 H nmr (dimethyl sulfoxide-d 6 ): δ 7.19 (br s, 1H, NH 2 , deuterium oxideexchangeable), 7.25 (td,1H,J = 7.7,1.1 Hz),7.34 (td,1H,J = 7.7,1.5 Hz),7.42 (d,1H,J = 7.2 Hz),8.09 (d,1H,J = 7.5 Hz), 12.20 (br s, 1H, NH, deuterium oxideexchangeable); 13 C nmr (dimethyl sulfoxide-d 6 ): δ 112.6 (C-6), 113.9 (C-9), 121.8 (C-7), 124.7 (C-8), 126.6 (C-5a), 133.1 (C-9a), 150.3 (C-10a), 153.7 (CO), 162.9 (C-2). Anal.…”

“…The synthesis of the 2-amino-s-triazino [1,2-a]benzimidazoles has been achieved through the ring closure of 2guanidinobenzimidazoles [4][5][6][7][8][9][10][11][12][13]. To date, only a limited number of reports [8,9,12] have discussed the ring closure of unsymmetrical 2-guanidinobenzimidazoles, with respect to 5-methyl-2-guanidinobenzimidazole (5b).…”

“…The synthesized 2-guanidinobenzimidazoles (5) were then cyclized using different reagents to give 2amino-s-triazino [1,2-a]benzimidazoles with different substitutions at position 4 (Scheme 1). The structures of the synthesized 2-amino- [1,3,5]triazino [1,2-a]benzimidazoles (6)(7)(8)(9)(10)(11) were elucidated with the help of ir and nmr spectral and elemental analyses. The ratios of the isomeric products (6-11b,c) prepared from 5b were determined, without separation of mixtures, using nmr spectroscopic techniques.…”

“…Refluxing of 2-guanidinobenzimidazoles (5) in acetone under piperidine catalysis led to the formation of 2-amino-3,4-dihydros-triazino [1,2-a]benzimidazoles (9) with two geminal methyl groups. Cycloadditions of these carbonyl reagents to 5b did not show regioselectivity and gave the isomeric compounds 7-9b and 7-9c in equal or almost equal proportion ( Table 1).…”