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mL). The DCM was evaporated under reduced pressure and the
crude of reaction such obtained was puried by column chro-
matography (28% EtOAc/hexane) to afford the angular
compound 37 (22 mg, 18.5%) as a yellow solid and the linear
isomer 38 (19 mg, 16%) as a yellow solid.
7,8-Dimethoxy-3-(methoxymethyl)-4-(4-methoxyphenyl)-1-
methyl-1H-naphtho[1,2-d]imidazole-2,6,9(3H)-trione (37). Mp
145–147 ꢁC. Rf ¼ 0.5 (28% EtOAc/hexane). IR (neat, n/cmꢀ1):
2922, 2852, 1720, 1664, 1623, 1611, 1514, 1455, 1379, 1342,
1284, 1242, 1242, 1081, 1047, 1028, 964, 811, 756, 698. 1H NMR
(500 MHz, CDCl3) d 7.75 (s, 1H), 7.30 (d, J ¼ 8.6 Hz, 2H), 6.98 (d, J
¼ 8.6 Hz, 2H), 4.84 (s, 2H), 4.12 (s, 3H), 4.09 (s, 3H), 3.87 (s, 3H),
3.72 (s, 3H), 3.03 (s, 3H). 13C NMR (126 MHz, CDCl3): d 181.4,
181.0, 160.1, 156.9, 148.3, 146.3, 132.3, 131.3, 130.5, 129.3,
128.8, 125.5, 125.1, 114.5, 113.8, 72.5, 61.5, 61.4, 56.2, 55.5, 34.3.
HRMS (ESI+): m/z calcd for C23H23N2O7 [M + H]+ ¼ 439.1505,
found 439.1487.
6,7-Dimethoxy-3-(methoxymethyl)-4-(4-methoxyphenyl)-1-
methyl-1H-naphtho[2,3-d]imidazole-2,5,8(3H)-trione (38). Mp
191–193 ꢁC. Rf ¼ 0.5 (60% EtOAc/hexane). IR (neat, n/cmꢀ1):
2939, 2836, 1707, 1664, 1654, 1611, 1600, 1514, 1469, 1454,
1382, 1340, 1282, 1241, 1178, 1123, 1080, 1045, 1027, 958, 908,
828, 812, 755. 1H NMR (500 MHz, CDCl3): d 7.77 (s, 1H), 7.15 (d,
J ¼ 8.6 Hz, 2H), 6.98 (d, J ¼ 8.6 Hz, 2H), 4.46 (s, 2H), 4.05 (s, 3H),
3.96 (s, 3H), 3.88 (s, 3H), 3.53 (s, 3H), 3.02 (s, 3H). 13C NMR (126
MHz, CDCl3): d 182.0, 181.6, 159.5, 155.4, 148.3, 145.4, 134.2,
131.4, 130.0, 128.2, 127.4, 126.0, 124.1, 113.8, 105.4, 72.0, 61.4,
61.4, 55.9, 55.4, 27.8. HRMS (ESI+): m/z calcd for C23H23N2O7 [M
+ H]+ ¼ 439.1505, found 439.1501.
Sequence followed in Scheme 9
6-Bromo-3-(methoxymethyl)-4-(4-methoxyphenyl)-1-methyl-
1,3-dihydro-2H-benzo[d]imidazol-2-one (35). A dried 100 mL
two-necked round bottom was charged with 6-bromo-4-(4-
methoxyphenyl)-1-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-
one 21 (1.76 g, 5.3162 mmol) and 50 mL dry dimethylacetamide.
To the reaction mixture was added Cs2CO3 (8.6 g, 26.581 mmol,
5.0 equiv.), followed by addition of MOM-Cl (2.0 mL,
26.581 mmol, 5.0 equiv.) dropwise at room temperature and
ꢁ
stirred at 50 C for 12 h. The reaction mixture was quenched
with H2O and extracted with EtOAc (200 mL). The organic layers
were collected and dried over Na2SO4, concentrated under
reduced pressure. The resulted crude was puried by column
chromatography (27% EtOAc/hexane) to afford the MOM-
protected compound 35 (1.44 g, 72%) as pale white solid. Mp
144–146 ꢁC. Rf ¼ 0.5 (50% EtOAc/hexane). IR (neat, n/cmꢀ1):
3056, 2996, 2938, 2855, 1700, 1604, 1515, 1449, 1372, 1289,
1
1246, 1172, 1087, 1066, 1021, 955, 910, 826, 753, 696. H NMR
(500 MHz, CDCl3): d 7.30 (d, J ¼ 8.6 Hz, 1H), 7.09 (d, J ¼ 1.8 Hz,
1H), 7.05 (d, J ¼ 1.8 Hz, 1H), 6.95 (d, J ¼ 8.6 Hz, 1H), 4.80 (s, 1H),
3.85 (s, 2H), 3.42 (s, 2H), 3.03 (s, 2H). 13C NMR (126 MHz,
CDCl3): d 159.7, 155.2, 132.2, 130.7, 129.2, 127.3, 127.1, 125.1,
114.3, 113.6, 109.7, 72.2, 55.9, 55.5, 27.5. HRMS (ESI+): m/z calcd
for C17H18BrN2O3 [M + H]+ ¼ 377.0501, found 377.0496.
Metal–halogen exchange and 1,2 addition of compound (36).
A ame-dried 250 mL two-neck round-bottom ask was charged
with MOM-protected benzimidazolone 35 (0.33 g, 0.8776 mmol)
dissolved in dry THF (30 mL) and stirred at ꢀ78 ꢁC (acetone/dry
ice bath). Aerwards it was added 1.6 M solution of n-BuLi in
hexane (1.4 mL, 2.1941 mmol, 2.5 equiv.) drop wise. The clear
solution was stirred at ꢀ78 ꢁC temperature for additional 15
Removal of MOM-group from kealiiquinone analogous
minutes, then
a solution of dimethylsquarate (0.1 g,
7,8-Dimethoxy-4-(4-methoxyphenyl)-1-methyl-1H-naphtho
[1,2-d]imidazole-2,6,9(3H)-trione (39). To a 25 mL of two-necked
round bottom ask was charged with 7,8-dimethoxy-3-
(methoxymethyl)-4-(4-methoxyphenyl)-1-methyl-1H-naphtho
[1,2-d]imidazole-2,6,9(3H)-trione 37 (9 mg, 0.0205 mmol) and
was dissolved in triuoroacetic acid (3 mL). The reaction
mixture was stirred at 60 ꢁC for 20 h and it was neutralized with
20 mL of sat. NaHCO3 solution followed by extracted with EtOAc
(30 mL). The organic layer was dried over Na2SO4, concentrated
under reduced pressure. The crude was puried by crystalliza-
tion method (EtOAc/hexane 1 : 2) to afford angular isomer of
kealiiquinone 39 (6 mg, 82%) as light red solid. Mp > 300 ꢁC. Rf
¼ 0.4 (50% EtOAc/hexane). IR (neat, n/cmꢀ1): 3159, 2953, 2921,
2851, 1708, 1665, 1646, 1623, 1515, 1460, 1377, 1330, 1249,
0.7021 mmol, 0.6 equiv.) in dry THF (3 mL) was added drop-wise
to the reaction mixture, and the stirring was continued at
ꢀ78 ꢁC for 30 minutes. The reaction was quenched by addition
of saturated NH4Cl solution (10 mL) and stirred for 10 minutes
allowing to reach room temperature. The layers were separated,
and the aqueous layer was extracted with EtOAc (100 mL). The
combined organic layers were dried over Na2SO4 and concen-
trated under reduced pressure to give crude material. The
resulted crude was puried by column chromatography (75%
EtOAc/hexane) to furnish the intermediate 36 (0.15 g, 61%) as
white sponge like solid. Mp 60–62 ꢁC. Rf ¼ 0.3 (75% EtOAc/
hexane). IR (neat, n/cmꢀ1): 3308, 2932, 2838, 1771, 1687, 1611,
1514, 1459, 1338, 1242, 1175, 1087, 1053, 1056, 982, 833, 758,
690. 1H NMR (500 MHz, CDCl3): d 7.32 (d, J ¼ 8.6 Hz, 2H), 7.22
(d, J ¼ 1.7 Hz, 1H), 7.01 (d, J ¼ 1.7 Hz, 1H), 6.96 (d, J ¼ 8.7 Hz,
2H), 4.82 (s, 2H), 4.10 (s, 3H), 4.02 (s, 3H), 3.86 (s, 3H), 3.46 (s,
3H), 3.39 (s, 1H), 3.03 (s, 3H). HRMS (ESI+): m/z calcd for
1
1195, 1104, 1059, 1031, 962, 908, 829, 735. H NMR (500 MHz,
CDCl3): d 8.16 (s, 1H), 7.93 (s, 1H), 7.46 (d, J ¼ 8.6 Hz, 2H), 7.06
(d, J ¼ 8.6 Hz, 2H), 4.13 (s, 3H), 4.10 (s, 3H), 3.89 (s, 3H), 3.75 (s,
3H). HRMS (ESI): m/z calcd for C21H19N2O6 [M + H]+ ¼ 395.1243,
found 395.1238.
C
23H25N2O7 [M + H]+ ¼ 441.1662, found 441.1658.
Thermolysis of 36. A ame dried 20 mL glass vial was charged
with the intermediate 36 (0.14 g). Without the addition of
solvent, the vial was placed in a preheated oil bath for 1 hour in
which temperature was previously adjusted and xed at 160 ꢁC.
Aer this period, the vial was removed from the hot bath
allowed to reach room temperature and dissolved in DCM (20
Kealiiquinone
6,7-Dimethoxy-4-(4-methoxyphenyl)-1-methyl-1H-naphtho
[2,3-d]imidazole-2,5,8(3H)-trione (1). To a 25 mL two-necked
round bottom ask was charged with 7,8-dimethoxy-3-
(methoxymethyl)-4-(4-methoxyphenyl)-1-methyl-1H-naphtho
30774 | RSC Adv., 2018, 8, 30761–30776
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