Synthese chiraler Barbiturat‐Mannichbasen

Abstract

810,760cm-'.-1H-NMR/60MHz(CDC13-100 %): G(ppm) = 12.50(s, lH, OH, austauschbar), 7.38 (s, 5H, aromat.), 7.12 (s, 4H, aromat.), 7.0-6.5 (bs, lH, OH, austauschbar), 6.52 (d, 1H,J=2Hz,H-4),4.60(d,1H,J=8Hz,H-7),4.14und4.11(2~q,2H,J=7Hz,-O-C~-CH~), 3.72 (dd, lH, J = 8/2Hz, H-7a), 1.20 (t, 3H, J = 7Hz, -O-CH,-C&). -MS (80eV, 160"): m/z= 424/422 (38/100 %, Durch Kondensation von Monoalkylmalonestern sowie von 2-Chlorcarbonyl-2-phenylketen mit N,N'-disubstituierten Harnstoffen wurden die 1,3,5-trisubstituierten Barbitursauren 1 synthetisiert, die nach verschiedenen Verfahren in die chiralen Barbiturat-Mannichbasen 5-7 verwandelt wurden. Die besten Ausbeuten ergab die Umsetzung der Barbitursauren 1 mit den Methyleniminiumchloriden 2-4 in siedendem Acetonitril. Zahlreiche Versuche zur Spaltung der Barbiturat-Mannichbasen 5-7 in die Enantiomere verliefen erfolglos. + ) Herrn Prof. Dr. Woldemar Schneider, Freiburg, mit den besten Wunschen zum 65. Geburtstag gewidmet. 03656233/84/0909-0789 $ 0?.50/0 6 Verlag Chemie GmbH, Weinheim 1984 I-CyclohexyE-3.5-dimethylbarbitursiiure (lax) Aus 70 g (0,4 mol) Methylmalonester und 63 g (0,4 mol) N-Cyclohexyl-N'-methylharnstoff 61 g (83 % d. Th.) lax, Schmp. 83". IR (KBr) 2950,2880 (CH), 1680 (CO) cm-l. NMR (CDCI,): 6 (ppm) = 4 3 (m; l H , alicycl.), 3,95 (4; lH, heterocycl.), 3,3 (s; 3H, NCH,), 2,6-1,0 (m; 10H, alicycl.), 1,55 (d; 3H, CCH,). Cl,Hl,N,O, (238,3) Ber. C 60,5 H 7,61 N 11,8 Gef. C 60.2 H 7,52 N 11.9. -Cyclohexyf-5-ethyl-3-methylbarbitursaure (lbx)Aus 75 g (0.4 mol) Ethylmalonester und 63 g (0,4 mol) N-Cyclohexyl-N'-methylharnstoff 81 g (86 %

Photo-Mediated Decarboxylative Giese-Type Reaction Using Organic Pyrimidopteridine Photoredox Catalysts

“…The tri-substituted barbiturate 29, a class of molecules with high pharmaceutical value, was directly obtained from diester 8ab and N,N′-dimethyl urea. 44 Furthermore, we performed a six-fold scale-up (3.0 mmol) of the parent photo-mediated coupling using 1-adamantanecarboxylic acid (6a) and dimethyl maleate (7a). The corresponding product 8fa was isolated in 45% yield after irradiation for 24 h. This significant decline in yield from 82% to 45% is likely attributed to the inferior penetration of light caused by an increased path length of light in the big-scale setup.…”

“…Moreover, the concerted alkylation and lactonization of 8fa with methyl magnesium bromide gave access to a 5,5′-disubstituted lactone 28 in 87% yield. The tri-substituted barbiturate 29 , a class of molecules with high pharmaceutical value, was directly obtained from diester 8ab and N,N′ -dimethyl urea . Furthermore, we performed a six-fold scale-up (3.0 mmol) of the parent photo-mediated coupling using 1-adamantanecarboxylic acid ( 6a ) and dimethyl maleate ( 7a ).…”