2(1H)-Quinolones are classified as aromatic heterocycles.With regard to reactions of 2(1H)-quinolones, substitution reactions [1][2][3][4][5][6][7][8] have been widely reported, but little attention has been focused on addition reactions. Diels-Alder (DA) reaction of 2(1H)-quinolones with diene afforded the phenanthridones in one pot. Recently, Weltin verified the ability of the 6(5H)-phenanthridones to inhibit poly(ADP-ribose)-polymerase (PARP) activity in lymphoma cells. [9][10][11][12] Furthermore, Cheng reported that 8,9-dimethoxyphenanthridinium salts (A, Chart 1) possess activity against leukemias P388. 13)We reported the synthesis of functionalized phenanthridones by novel DA reaction of 1-methyl-2(1H)-quinolones having an electron-withdrawing group (such as methoxycarbonyl, acetyl, cyano) at the 4-or 3-position that acts as a dienophlie.14-17) It is well known that the nitro group function as a leaving group and a strong electron-withdrawing group. Herein, we report the synthesis of 6(5H)-phenanthridones by DA reaction of 3-nitro-2(1H)-quinolones under atmospheric and high pressure (AP and HP) conditions, and we investigate of the reactivity of the 2(1H)-quinolones using molecular orbital (MO) calculation.DA Reaction Firstly, DA reactions of 3-nitro-(1a) and 3,6-dinitro-1-methyl-2(1H)-quinolones (1b) 18,19) with 1,3-butadienes (2a, b) were investigated under AP and HP conditions, as shown in Table 1 and Chart 1. DA reactions of 1a, b with 1-methoxy-1,3-butadiene (2a) were carried out at 180°C for 5 d in o-xylene (entries 1, 4), and gave 6(5H)-phenanthridones (3a, 20) 83%; 3b, 68%), respectively. The same reaction of 3a at 160°C for 3 d (entry 2), also afforded 3a (63%). On the other hand, DA reaction of 1a with 2a was performed under HP conditions (10 kbar) at 90°C for 2 d (entry 3), and gave endo-DA adduct (4a, 57%) and exo-DA adduct (4b, 20%), respectively. Heating of 4a, b at 180°C in sealed tube produced 3a (67%, 64%, respetively) aromatized by elimination of hydrogen and nitrogen dioxide (HNO 2 ), followed by release of MeOH. These facts indicated that 3a, b resulted from release of HNO 2 and MeOH of corresponding DA adducts (such as 4a) under AP conditions. Furthermore, DA reactions of 1a with 2,3-dimethoxy-1,3-butadiene (2b) at 180°C under AP condition gave 1-methyl-8,9-dimethoxy-6(5H)-phenanthridone (6a 3) ; 31%, 45%, entries 5, 6) which was the synthetic intermediate for A possessing a bioactivity. DA reactions of 1b with 2b at 180°C afforded 1-methyl-8,9-dimethoxy-2-nitro-6(5H)-phenanthridone (6b; 17%, 13%, entries 7, 8) in poor yields. But, DA reactions of 1a, b with 2b under HP condition (10 kbar) at 90°C for 2 d afforded DA adducts (5a, 57%; 5b, 55%, entries 9, 10) in reasonable yields. Heating of 5a, b at 180°C produced 6a (48%) and 6b (40%) aromatized by release of HNO 2 , followed by dehydrogenation, respectively. The stereochemistries of the group at C-7 in 4a, b were determined by nuclear Overhauser effect (NOE) measurement of 1 H-NMR spectra. The spectrum of 4a indicated a correlatio...
1(2H)-Isoquinolone derivatives are classified as aromatic heterocycles. Substitution reactions 1,2) of 1(2H)-isoquinolone derivatives have been reported, however, little attention has been focused on addition reactions. Dyke et al. reported a Diels-Alder (DA) reaction of 2-methyl-1(2H)-isoquinolone derivatives as the diene.3) To the best of our knowledge, however, there have been no reports of a DA reaction of 1(2H)-isoquinolones acting as dienophiles. DA reaction of 1(2H)-isoquinolone derivatives with dienes afforded phenanthridones. A number of Amaryllidaceae alkaloids contain phenanthridine skeletons, and are thought to be potentially valuable synthetic intermediates. Moreover, these alkaloids may possess novel pharmacological activities. 8) Herein, we report a novel Diels-Alder reaction of 4-nitro-1(2H)-isoquinolones acting as the dienophile. This Diels-Alder reaction is a novel synthetic methodology employing the phenanthridine skeleton. Examination of the regioselectivity of 4-nitro-1(2H)-isoquinolones 9) with 1-methoxy-3-silyloxy-1,3-butadienes using molecular orbital (MO) calculations is also discussed in the current work.DA Reaction of 4-Nitro-1(2H)-isoquinolones First, DA reactions of 2-methyl-(1a) 9) and 2-unsubstituted-1(2H)-isoquinolones (1b) 9) bearing a nitro group at the 4-position with 1-methoxy-1,3-butadienes (2a-c) were examined under atmospheric pressure conditions, as shown in Table 1 (entries 1-8) and Chart 1. Reaction of 1a with 1-methoxy-1,3-butadiene (2a) gave the 6-methyl-5(6H)-phenanthridone (4a 10) : 59%; entry 1 and 26%; entry 2) at 180°C for 3 d in 1,2-dimethoxyethane (DME) and o-xylene (pathway A). Reaction of 1b with 2a gave 5(6H)-phenanthridone ( 4b 11) : 82%; entry 3) at 160°C for 3 d in DME in high yield. Reaction of 1a with 1-methoxy-3-trimethylsilyloxy-1,3-butadiene (2b: TMS) was carried out in o-xylene and reaction mixture was treated with trifluoroacetic acid (TFA) to give 8-hydroxy-6-methyl-5(6H)-phenanthridone ( 5a 12) : 72%; entry 4) as a single product (pathway B). However, in DME, reaction of 1a with 2b (entry 5) gave 5a (63%) and 8-methoxy-6-methyl-5(6H)-phenanthridone ( 7a 13) : 7%). Further, reaction of 1a with 1-methoxy-3-t-butyldimethyl-silyloxy-1,3-butadiene (2c: TBS) in DME (entry 6) gave 5a (52%), 7a (2%) and 8-tbutyldimethylsilyloxy-6-methyl-5(6H)-phenanthridone (6a: 29%) in total 83% yield. Moreover, reaction of 1b with 2b gave 8-hydroxy-5(6H)-phenanthridone (5b 14) : 75%; entry 7), whereas reaction of 1b with 2c gave 5b (37%) and 6b (6%) in DME (entry 8). Next, reaction of 1a, b with symmetric dienes (2d, e) were subsequently investigated as shown in Table 1 (entries 9-12) and Chart 1. The reaction of 1a with 2,3-dimethyl-1,3-butadiene (2d) afforded 6,8,9-trimethyl-5(6H)-phenanthridone (8a: 18%; entry 9 and 36%; entry 10) at 180°C for 3 d in o-xylene and DME (pathway C). But, the reaction of 1a with 2d did not give 8,9-dimethyl-5(6H)-phenanthridone (8b), and 1b was recovered. Further, the re- February 2006Chem. Pharm. Bull. 54(2) 209-212 (2006) 209 ...
Phenanthridine derivatives R 0440Novel Diels-Alder Reaction of 4-Nitro-1(2H)-isoquinolones. -The novel Diels-Alder reaction of 4-Nitro-1(2H)-isoquinolones (I) with butadiene derivatives (II), (IV) or (VII) yields phenanthridone derivatives. -(FUJITA*, R.; WAKAYANAGI, S.; WAKAMATSU, H.; MATSUZAKI, H.; Chem. Pharm. Bull. 54 (2006) 2, 209-212; Tohoku Pharm. Univ., Aoba, Sendai 981, Japan; Eng.) -M. Bohle 28-137
Synthesis of 5(6H)-Phenanthridones Using Diels-Alder Reaction of 3-Nitro--2(1H)-quinolones Acting as Dienophiles. -The Diels-Alder reaction of quinolones of type (I) or (IX) yielding phenanthridone derivatives is studied. -(FUJITA*, R.; YOSHISUJI, T.; WAKAYANAGI, S.; WAKAMATSU, H.; MATSUZAKI, H.; Chem. Pharm. Bull. 54 (2006) 2, 204-208; Tohoku Pharm. Univ., Aoba, Sendai 981, Japan; Eng.) -M. Bohle 28-136
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.