Dihydropyridines from dimethyl acetylenedicarboxylate and Schiff bases

Abstract

The product of the reaction between benzylidenemethylamine and dimethyl acetylenedicarboxylate has been identified as tetrarnethyl 1.6-dihydro-l -methyl-6-phenylpyridine-2,3,4,5-tetracarboxylate from degradative studies and physical data. Cinnarnylideneaniline similarly yields tetrarnethyl 1,6-dihydro-l -phenyl-6-styrylpyridine-2,3,4,5-tetracarboxylate.

Addition of dimethyl acetylenedicarboxylate to imino ethers. Trapping of a 1,4-dipolar intermediate

“…Upon addition of ether to the residue, a white solid precipitated out of solution. Recrystallization from methanol gave 548 mg (50%) of 2a: mp 144.5-146.5°; ir (CHCI3) 2950, 1750, 1725, 1600 cm"1; uv (ethanol) 215 nm (e 13,500), 278 (14,000), 345 (10,200); NMR (CCU) 1.50 (s, 9 H), 3.58 (s, 3 H), 3.67 (s, 6 H), 3.92 (s, 3 H), 5.43 (s, 1 H); mass spectrum (70 eV) m/e 399.1526 (caled for CigHssNOg, 399.1529); m/e (rel intensity) 399 (M+, 3), 369 (1), 368 (3), 354 (1), 241 (3, 240 (16, 313 (3, 298 (3), 286 (2), 285 (9), 284 (77), 266 (4), 253 (2), 252 (12), 251 (100), 237 (5), 224 (1), 205 (2), 194 (1), 178 (2), 167 (1), 166 (1), 151 (1) , 137 (1), 135 (2), 79 (1), 77 (1), 59 (5), 58 (1), 57 (30), 56 (2), 55 (2) , 45 (2), 44 (2), 42 (3), 41 (11), 39 (2).…”

“…Reaction of DMAD with lb. Following the procedure for la above, 392 mg (3.04 mmol) of lb and 470 mg (3.30 mmol) of DMAD in 10 ml of dichloromethane resulted in 460 mg (67%) of 2b: mp 155.5-156.5°; ir (CHCI3) 2950, 1740, 1680, 1595 cm"1; NMR (100 MHz) (CDC13) 1.46 (t, JAX = Jbx = 7.0 Hz, 3 ) (X part of ABX3), 1.54 (s, 9 H), 3.66 (s, 6 ), 3.71 (s, 3 H), 3.86 (s, 3 ), 4.07 (dq, JBX = 7.0, JAB = 9.5 Hz, 1 ) (B part of ABX3), 4.53 (dq, J ax = 7.0, Jab -9.5 Hz, 1 ) (A part of ABX3, AB spectrum obtained from time averaged computer technique), 5.66 (s, 1 H); mass spectrum (70 eV) m/e 413.1689 (caled for C19H27NO9, 413.1686); m/e (rel intensity) 413 (M+, 10), 382 (12), 355 (8), 354 (47), 326 (12), 299 (17), 298 (100), 267 (32), 266 (100), 238 (83), 206 (33), 178 (25), 59 (25)•, 57 (83), 41 (42).…”

“…Reaction of DMAD with 12. Following the procedure for 6a with the addition of 1 drop of ethyldiisopropylamine, 105 mg (0.83 mmol) of 12 and 120 mg (0.84 mmol) of DMAD yielded 58 mg (26%) of a 1:1 mixture of fumarate (13) and maleate (14) isomers: bp 100-110°(10-3 mm); ir (CCU) 2970,1740 (sh), 1725,1640,1620, 1440 cm"1; NMR (CCU) for 13 1.60 (s, 6 H), 1.68 (s, 3 H), 3.58 (s, 3 H), 3.68 (s, 6 ), 5.90 (s, 1 H) (assigned as fumarate isomer);38 for 14 1.60 (s, 6 ), 1.68 (s, 3H), 3.60 (s, 3 H), 3.74 (s, 3 ), 3.80 (s, 3 ), 5.13 (s, 1 H) (assigned as maleate isomer);38 mass spectrum (70 eV) m/e 269.1256 (caled for C13H19NO5, 269.1263); m/e (rel intensity) 269 (M+, 10), 254 (3), 239 (12), 222 (3), 210 (67), 194 (5), 183 (7), 179 (10), 178 (100), 151 (12), 150 (20), 97 (5), 96 (7), 95 (8), 69 (12), 68 (13), 67 (13), 59 (8), 55 (10), 53 (18), 44 (12), 43 (5), 42 (8), 41 (47), 40 (3), 39 (13).…”

“…Vacuum distillation afforded 376 mg (59% yield) of a mixture of products 31 (80%) and 32 (20%), bp 70-80°( 0.07 mm). Following the procedure above, but with excess DMAD, 375 mg (2.90 mmol) of lb and 831 mg (5.85 mmol) of DMAD gave 254 mg (29%) of product 33: bp 150-160°(0.3 mm); ir (neat and dilute CC14) 3220, 2940,1745-1730,1660,1598 cm'1; uv (ethanol) 229 nm (e 8200); NMR (CC14) 1.35 (s, 9 H), 3.64 (s, 6 H), 3.68 (s, 3 H), 3.74 (s, 3 ), 6.61 (s, 1 ), 9.0 (s, 1 H, NH); mass spectrum (70 eV) m/e 357.1425 (caled for CisHasNOg, 357.1424); m/e (rel intensity) 358 (7), 357 (M+, 40), 342 (5), 326 (7), 301 (14), 298 (3), 278 (5), 270 (7), 243 (10), 242 (100), 238 (18), 211 (8), 210 (82), 182 (5), 178 (15), 150 (7), 59 (12), 58 (3), 57 (25), 41 (18), 39 (3). Product 33 was independently synthesized by treating 210 mg (2.86 mmol) of tert-butylamine with 813 mg (5.70 mmol) of DMAD in dichloroethane at 90°for 16 hr.…”

“…[4][5][6] The geometry of 9 and the formation of both products 7 and 8 eliminate the possibility of an intramolecular proton abstraction. 2-Azetines are known to ring open readily.13-15•22-24•26 Analogously to 6, the azetine 12 gives esters 13 and 14 in 26% yield. The low yield can be attributed to steric hindrance by the 3-methyl substituent in the proton abstraction.…”