416
Y.K. Tyagi et al. / European Journal of Medicinal Chemistry 40 (2005) 413–420
spectrum C-2 appeared at d 157.05 and three other carbonyl
appeared at d 166.21, 167.12 and 167.25 for carbonyl car-
bons. Finally, the MS peak at m/z 232 supported by its struc-
ture. The IR spectrum of compound 15 showed two charac-
teristic absorptions at 1788 and 1740 cm–1 for two carbonyl
groups. The 1H NMR spectrum showed characteristic singlet
of 4-methyl coumarins appeared at d 6.10 for C-3H proton
and finally the structure was confirmed by its 13C NMR spec-
trum, C-2 appeared at d 156.90 and other two carbonyl car-
bons appeared at d 167.10, 167.61.
3.1.4. 5-N-acetyl-6-acetoxy-4-methylcoumarin 9
Yield: 2.25 g (78%). m.p.: 170–172 °C; UV (MeOH): kmax
285, 253 nm; IR (KBr): Vmax 3230, 3087, 3006, 2367, 1771,
1734, 1649, 1566, 1527, 1443, 1372, 1273, 1115, 1059, 1017,
1
974, 947, 721, 523, and 431 cm–1; H NMR (60 MHz,
CDCl3): d 2.11 (3H, s, CH3-CO), 2.22 (3H, s, 3H, s, NH-
COCH3), 2.40 (3H, s, C-4 CH3), 6.01 (1H, s, C-3H), 7.01
(1H, d, J = 8.4 Hz, C-7H) 7.12 (1H, d, J = 8.4 Hz, C-8H);
13C NMR (75,5 MHz, CDCl3): d 18.76, 20.18 and 20.75
(C-6OCOCH3, C-5NHCOCH3 and C-4CH3), 114.38,
115.16 and 116.73 (C-7, C-8, C-3), 124.06 and 125.90 (C-10,
C-9), 142.22 (C-4), 149.62 and 150.62 (C-5, C-6), 157.10
(C-2, C=O), 166.50 and 167.65 (C-5, C-6, 2xC=O); EIMS,
m/z (rel. int.) 276 [M + 1] (8%), 233 (43%), 215 (100%), 162
(62%) 134 (30%), 106 (18%), 89 (10%), 79 (26%), 53 (20%),
43 (100%).
3.1. Chemistry
The synthesis of the novel compounds is outlined in
Scheme 1. The preparation of derivatives of nitro and amino
coumarins is based on the methodology used by Kaufman et
al. [12] with some modifications. The sequence of reactions
started from compound 2. Basic nitration of 2a–c afforded
the nitro derivatives 4, 5, 10 and 14, compounds 10 and
14 were treated with acetic anhydride/pyridine (Ac2O/Py) to
obtain the compounds 11 and 15, respectively, in quantitative
yield. On the other hand, according to Kaufman et al. amino
derivatives 6, 7 and 12 were prepared by the reduction of
respective nitro derivatives 4, 5 and 10 with the concentrated
ammonium hydroxide and sodium hydrosulfite, after stirring
the reaction mixture for 90 min. The compounds 8, 9 and
13 were obtained by treating 6, 7 and 12 with Ac2O/Py mix-
ture at 25 °C. The spectral data of all the novel compounds
are given below.
3.1.5. 5,7-Dinitro-6-acetoxy-4-methylcoumarin 11
Yield 5.04 g (87%). m.p.: 205 °C; UV (MeOH): kmax 268,
208; IR (Nujol): Vmax 2922, 1803, 1765, 1743, 1532, 1463,
1412, 1375, 1340, 1311, 1222, 1190, 1053, 975, 892; 1H NMR
(300 MHz, CDCl3): d 2.38 (6H, s, 3H each, CH3 and
OCOCH3), 6.56 (1H, s, C-3H) and 8.24 (1H, s, C-8H); 13
C
NMR (75,5 MHz, CDCl3): d 18.27 and 20.27 (C-4CH3 and
C-6COCH3), 116.08 and 116.94 (C-3, C-8), 122.20 and
123.00 (C-9, C-10), 133.31 (C-4), 142.08, 146.82 and 150.69
(C-5, C-7, C-6), 156.56 (C-2, C=O), 167.02 (C-6, C=O).
3.1.6. 5,7-Diamino-6-hydroxy-4-methylcoumarin 12
Yield 1.62 g (70%). m.p.: >260 °C; UV: MeOH kmax 311,
258, 240; IR (Nujol): Vmax 3433, 3353, 2925, 1737, 1633,
1552, 1461, 1377, 1292, 1243, 1142, 1084, 922, 853, 757,
691, 54 cm–1; 1H NMR (300 MHz, DMSO-d6): d 2.58 (3H, s,
C-4, CH3), 6.41 (1H, s, C-3H), 9.50 (1H, s, C-8H); 13C NMR
(75,5 MHz, DMSO-d6): d 18.25, (C-4CH3), 115.35 and
117.59 (C-3) and (C-8), 121.22 and 122.70 (C-9 and C-10),
133.31(C-4), 141.68, 145.42 and 147.42 (C-5, C-7 and C-6),
158. 06 (C-2, C=O); EIMS, m/z (rel. int.): 206 [M+] (4%),
191 (100%), 162 (59%), 148 (14%), 134 (18%), 128 (8%),
58 (100%) 53 (18%).
3.1.1. 4-Methyl coumarin derivatives
All synthesized compounds are 4-methyl coumarin deriva-
tives and there is no as such novel 4-methyl coumarin deriva-
tives for spectral data except given below.
3.1.2. 7,8-Dihydroxy-4-methylcoumarin DHMC, 2a
The structure of DHMC was confirmed as per reported
spectral data [11] and the structure of DAMC was confirmed
by spectral data reported earlier [16].
3.1.7. 5,7-N-diacetyl-6-acetoxy-4-methylcoumarin 13
Yield 1.29 g (40%). m.p.: > 260 °C; UV (MeOH): kmax
330, 298, 214 nm; IR (KBr): Vmax 3342, 3243, 2931, 1740,
1701, 1665, 1615, 1574, 1462, 1371, 1251, 1197, 1099, 1072,
3.1.3. 8-N-acetyl-7-acetoxy-4-methylcoumarin 8
Yield: 2.01 g (70% yield). m.p.: 185–187 °C; UV: kmax
276, 215.; IR (Nujol): Vmax 3230, 2928, 1906, 1769, 1735,
1658, 1606, 1566, 1529, 1462, 1373, 1354, 1233, 1115, 1060,
947, 858, 720, 640, 523 cm–1; 1H NMR (300 MHz, DMSO-
d6): d 2.21 (3H, s, OCOCH3), 2.30 (3H, s, NHCOCH3), 2.42
(3H, s, C-4 CH3), 6.30 (1H, s, C-3H),7.21 (1H, d, C-5H) 7.42
(1H, d, C-6H); 13C NMR (75 MHz, DMSO-d6): d 20.80,
22.23 and 22.80 (C-7OCOCH3, C-8NHCOCH3, and
C-4CH3,), 116.43, 117.20 and 118.78 (C-5, C-6, C-3),
126.10 and 127.95 (C-10, C-9), 144.27 (C-4), 151.67 and
152.66 (C-8, C-7), 159.08 (C-2, C=O), 168.55 and 169.70
(C-8 and C-7, 2XC=O); EIMS: m/z (rel. int.) 276 [M + 1]
(10%), 233 (45%), 215 (100%), 162 (62%), 134 (32%), 106
(22%), 89 (13%), 77 (30%), 58 (32%), 43 (100%).
1
942, 865, 693, 596, 456 cm-1. H NMR (60 MHz, DMSO-
d6): d 2.29 (3H, s, OCOCH3), 2.40 (6H, s, NHCOCH3), 2.49
(3H, s, C-4 CH3), 6.30 (1H, s, C-3H), and 8.23 (1H, s, C-8H);
13C NMR (75,5 MHz, DMSO-d6): d 18.79, 19.72, 20.43 and
22.01 (C-4CH3, C-5NHCOCH3, C-7NHCOCH3 and
C-6OCOCH3), 111.54 and 113.20 (C-8, C-3), 125.56 and
126.15 (C-10, C-9), 133.04 (C-4), 149.50, 149.95 and 150.25
(C-5, C-7, C-6), 157.05 (C-2, C=O), 166.21, 167.12 and
167.25 (C-5, C-7, C-6, 3xC=O). EIMS m/z (rel. int.) 332 [M+]
(100%), 299 (71%), 268 (4%), 255 (8%), 199 (6%), 143
(19%), 129 (6%), 87 (76%), 74 (100%), 69 (21%), 57 (28%),
43 (45%).