Ring transformation of condensed dihydro‐as‐triazines

Abstract

T h e 2-amino-as-triazino[6,5-c]quinoline as well as 3-aminopyrido[4,3-e]-as-triazine had previously been synthetized by BerCnyi (1) and Benko et a1 (2). In this paper, the ring transformation occuring in aqueous media of the dihydro intermediates and their salts, respectively appearing during the synthesis of 2-substitutedamino-as-triazino[6,5-c]quinolines, are reported.J. Ileterocyclic Chrm.. 18, 1537 (1981).In the course of preparation of our model compounds, 4-chloro-3-nitroquinoline (1) (3) was made to react with the appropriately substituted quanidine 2 and the intermediates obtained (3) were cyclized under alkaline conditions to yield as-triazino[6,5-c]quinoline-4-oxides (4).The reduction of the N-oxides 4a-h resulted in the required model compounds 5a-h which could only be isolated in the form of their salts. Without salt formation, the base underwent oxidation and the ring system became aromatic 6a-h. Scheme I

Preparation of substituted 1,3‐dihydro‐2H‐imidazo[4,5‐c]pyridin‐2‐ones

“…Preparation of Substituted 1, (5), 119 (10), 94 (5), 93 (22), 91 (8), 79 (10), 66 (7), 64 (15), 52 (6) 54 (d, 1H, H-5, J = 6.0 Hz), 8.61 (d,1H,J = 6.0 Hz),9.34 (s,1H,9.82 (br s,1H,NH) ppm; 13 C nmr (deuteriochloroform): δ 28. 5, 83.7, 113.6, 132.2, 142.8, 148.3, 151.6, 155.2 ppm; ir: (potassium (12), 140 (10), 139 (15), 135 (7), 121 (6), 119 (8), 93 (8), 91 (7), 79 (6), 66 (7), 64 (11), 59 (31), 58 (8), 57 (100), 56 (9), 55 (5), 52 (6) To a solution of 5 b (0.503 g, 2.24 mmol) in n-butylamine ( 1 2 mL) was added potassium permanganate (1.32 g, 8 . 3 8 mmol) and the mixture stirred vigorously at room temperature.…”

“…This gave 0.633 g of an oil, which was purified by flash chromatography (2 % acetone in dichloromethane) to give 0.189 g (>98 % pure by 1 : δ 13.9, 19. 8, 21.8, 31.1, 69.7, 94.2, 125.2, 141.0, 150.6, 152.0, 162.1 ppm; one (18), 211 (100), 208 (10), 206 (5), 198 (18), 193 (6), 192 (5), 181 (19), 168 (11), 167 (67), 166 (18), 163 (15), 122 (5), 121 (48), 120 (11), 119 (5), 106 (7), 94 (5), 93 (7), 92 (5), 67 (7), 45 (11), 43 (28) ppm; hrms: observed: M + 296.1478. Calculated for C 1 3 H 2 0 N 4 O 4 : 2 9 6 .…”

“…1 H nmr (deuteriochloroform): δ 0.97 (tr, 3H, CH 3 , J = 7.3 Hz), 1.37-1.49 (m, 2H, CH 2 ), 1.54 (s, 9H, 3 x CH 3 ), 1.59-1.68 (m, 2H, CH 2 ), 3.36 (br s, 2H, CH 2 ), 5.30 (br s, 1H, NH), 7.44 (s, 1H, H-3), 9.02 (s, 1H, H-6), 10.09 (br s, 1H, NH) ppm; 1 3 C nmr (dimethyl sulfoxide-d 6 ): δ 15. 1, 19.6, 27.7, 31.0, 83.1, 93.4, 124.8, 140.9, 150.5, 151.2, 161.9 ppm; one signal which was covered by dimethylsufoxide was observed at 42.5 ppm for a run in deuteriochloroform; ir: (potassium bromide) 3315 (m), (26), 254 (10), 238 (6), 237 (30), 225 (46), 212 (35), 211 (81), 210 (16), 208 (5), 198 (39), 194 (6), 193 (22), 192 (6), 182 (5), 181 (49), 168 (31), 167 (100), 163 (8), 154 (34), 152 (5), 151 (6), 150 (5), 149 (21), 147 (7), 139 (6), 137 (11), 135 (13), 124 (9), 122 (5), 121 (60), 120 (16), 119 (5), 106 (6), 94 (5), 93 (8), 81 (5), 67 (6), 57 (53), 56 (8), 55 (8), 52 (5) To a solution of 5 a ( 0 . 119 g, 0.60 mmol) in ethyl acetate ( 1 0 mL) was added 5% palladium on carbon (0.021 g) and the mixture stirred under hydrogen (10 bar) for 24 hours.…”

“…1, 116.6, 134.1, 136.7, 138.6, 139.9, 156.3 ppm; ir: (potassium A solution of 5c (0.657 g, 2.75 mmol) in methanol (20 mL) was treated in the same manner as described for reduction of 5a. 3, 81.5, 114.2, 131.8, 134.9, 140.7, 143.1, 152.5 (6), 153 (90), 136 (21), 135 (56), 110 (5), 109 (84), 108 (5), 107 (7), 97 (7), 95 (5), 85 (7), 83 (7), 82 (8), 81 (11), 80 (11), 71 (11), 69 (11), 67 (6), 59 (56), 57 (100), 56 (14), 55 (20), 54 (8) A solution of 6c (0.615 g, 1.98 mmol) in ethyl acetate (30 mL) was treated in the same manner as 5a. Evaporation of the solvent gave 0.385 g of a light purple oil (> 98% pure by 1 H nmr, 69% yield) which deteriorated quickly after isolation.…”

“…Only a few examples of imidazo [4,5-c]pyridin-2-ones with substituents on the pyridine ring are given in the literature. I m i d a z o [ 4 , 5 -c]pyridin-2-ones in which the pyridine moiety is part of a larger polycyclic skeleton such as quinolines and α-carbolines have been reported [11,12]. Va r i o u s l y substituted 4-hydroxy-3-nitropyridin-2-ones originating from cyclo additions of nitromalonesters and a ketimine have been used as substrates for preparation of i m i d a z o [ 4 , 5 -c]pyridin -2-ones [13,14].…”