Application of Organolithium and Related Reagents in Synthesis; Part 17: Synthesis of Azaisoindolo[2,1-a]quinoline Derivatives

Methods for the construction of [1,2]isoindolo-condensed benzazepines, benzazocines, quinolines, and isoquinolines. 2. Isoindoloquinolines, isoindoloisoquinolines. (Review)

“…An intramolecular Friedel-Crafts reaction with 2-aryl-2,3-dihydro-3-oxo-1H-isoindolo-1-acetyl chlorides 6 leads to isoindolo[2,1-a]quinolines and their aza analogs 7 [1,3]. The starting compounds for the synthesis of the acetyl chlorides 6a-f are N-arylphthalimides 3a-f, which are converted into the required acid _______ * Compounds 6f-j were not isolated in the individual form.…”

“…chlorides 6 by successive sodium borohydride reduction, the action of the Wittig reagent, and the action of thionyl chloride [1]. The starting compounds for the synthesis of the aza derivatives 6g-j are picoline and isonicotine anilides 3g-j, the reaction of which with butyllithium and DMF gives the intermediate 2-aryl-3-hydroxy-2,3-dihydroazaisoindol-1-ones 4g-j [3]. Isoindolo[2,1-a]quinolines can be obtained in one stage from 2-aryl-3-hydroxyisoindol-1-ones 10 [4].…”

A simple and convenient one-pot synthesis of substituted isoindolin-1-ones via lithiation, substitution and cyclization of N'-benzyl-N,N-dimethylureas

“…Several traditional methods are available for the synthesis of isoindolinones [ 16 – 25 ], based on the use of Grignard reagents [ 26 ], Diels–Alder reactions [ 27 ], Wittig reagents [ 28 ], reduction processes [ 29 – 30 ], rearrangement processes [ 31 ] and photochemical reactions [ 32 – 33 ]. However, such methods generally require multiple reaction steps and are unsatisfactory both in yield and generality.…”

Novel Approach to Isoindolo[2,1-a]quinolines: Synthesis of 1- and 3-Halo-Substituted 11-Oxo-5,6,6a,11-tetrahydroisoindolo[2,1-a]quinoline-10-carboxylic Acids

“…Only a few synthetic approaches to isoindolo[2,1-a]quinolines have been reported. [1][2][3][4][5][6][7][8][9][10][11][12][13] As a rule they require poorly available starting materials and involve a multi-step synthesis. Polycyclic nitrogen heterocycles with isoindolo[2,1-a]quinoline moiety have been shown to have important biological properties.…”

“…12d([M + ] (for 35 Cl), 1), 310(6), 304(13), 260(5), 246(20), 206 (100), 190(5), 138(10), 121(10), 111(8), 103 (8), 99 915), 91 (12), 77(11), 55(7), 44(11), 39(10), 28(14) 12e([M + ] (for 79 Br), 7), 348 98), 310(13), 292(9), 250 (100), 190 (32), 170(7), 155(13), 121 (46), 91 (35), 77 (39), 55 (25), 39 (44) 12f ([M + ], 3), 288 (14), 244 (5), 230 (24), 190 (100), 122 (13), 103 (7), 99 (12), 95 (7), 77 (8), 55 (6), 44 (6), 39 (7), 27 (5) 12g ([M + ], 12), 396 (13), 352 (10), 338 (20), 298 (100), 219 (6), 203 (12), 171 (28), 142 (5), 121 (37), 91 (26), 77 (22), 55 (13), 39 (15) 14a ([M + ] (for 35 Cl), 90), 326 (47), 308 (18), 297 (100), 282 (26), 266 (6), 252 (11), 238 (6), 217 (9), 178 (5), 141 (10), (10), 108 (9), 102 (6), 44 (13), 36 (7), 28 (12) 14b ([M + ] (for 79 Br), 31), 370 (11), 354 (5), 341 (51), 326 (18), 297 (24), 276 (6), 262 (11), 247 (14), 232 (36), 217 (39) 14c ([M + ], 88), 310 (42), 292 (18), 281 (100), 266 (30), 250 (11), 236 (16), 222 (13), 162 (6), 133 (13), 117 (6), 44 (7), 28 (6)14d ([M + ] (for 35 Cl), 13), 306 (59), 297 (100), 282 (10), 262 (45), 254 (26), 241 (10), 232 (10), 217 (23), 204 (14), 190 (12), 178 (23), 164 (16), 151 (12), 141 (26), 123 (24), 115 (57), 102 (48), 96 (25), 89 (42), 82 (6), 73 (39), 63 (29), 55 (8), 51 (27), 44 (55), 39 (34) 14e ([M + -44] (for 81 Br), 2), 306 (100), 262 (3), 217 (1), 109 (2), 95 (2), 81 (2), 69 (4), 43 (4) 14f ([M + ], 7), 310 (6), 281 (100), 266 (15), 238 (8), 226 (6), 197 (7), 170 (5), 128 (10), 115 (7), 77 (6) 14g ([M + ], 100), 418 (27), 389 (52), 374 (9), 262 (6), 232 (7), 217 (8), 204 (5), 128 (3), 115 (6), 109 (4), 77 (2), 44 (2) 15a, 16a ([M + ] (for 35 Cl), 28), 311 (6), 294 (4), 283 (100), 268 (25), 254 (9), 232 (7), 217 (5), 204 (13), 178 (9), 164 (11), 151 (8), 140 (4), 128 (6), 115 (16), 102 (31), 89 (20), 75 (30), 63 (15), 51 (16), 39 (17) 15b, 16b ([M + ] (for 79 Br), 66), 371 (69), 356 (7), 329 (100), 312 (13), 298 (7), 284 (15), 248 (19), 232 (23), 217 (9), 204 (33), (6), 146 (5), 129 (4), 115 (9), 102 (19), 77 (9), 51 (4), 39 (3) 15c, 16c ([M + ]; 63), 296 (5), 279 (9), 267 (100), 252 (26), 238 (11), 222 (21), 178 (5), 162 (6), 146 (6), 101 (5), 75 (5), 44 (6) 15d, 16d ([M + ] (for 35 Cl), 42), 312 (10), 294 (6), 283 (100), 268 (18), 232 (8), 204 (11), 194 (6), 178 (7), 164 (9), 151 (7), 134 (9), 123 (8), 109 (9), 102 (38), 96 (11), 89 (13), 82 (13), 75 (18), 63 (11), 58 (29), 51 (13), 36 (19) 15e, 16e ([M + ] (for 79 Br), 19), 327 (10), 292 (100), 248 (13), 204 (8), 115 (7), 89 (7), 77 (9), 63 (6), 51 (7), 39 (8) 15f, 16f ([M + ], 23), 267 (100), 238 (7), 224 (14), 222 (11), 162 (6), 133 (4), 44 (7), 28 (4) 15g, 16g ([M + ], 100), 375 (60), 248 (11), 232 (6), 204 (10), 128 (7), 102 (6), 44 (6), 41 (7) Mass Spectral Data of Compounds 11, 12, and 14-17 (EI, 70 eV) (continued) Product m/z, rel. intensity (%) The intramolecular cyclization of isoindolones 11a-f and 12a-f leading to isoindolo[2,1-a]quinoline-10-carboxylic acids 14a-f, 15a-f and 16a-f was carried out at 125-155°C in the presence of concentrated ortho-p...…”