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DOI: 10.1055/s-0029-1220068
Synthesis of Chromeno[3,4-b]pyrrol-4(3H)-ones by Cyclocondensation of 1,3-Bis(trimethylsilyloxy)buta-1,3-dienes with 4-Chloro-3-nitrocoumarin
Publication History
Publication Date:
25 May 2010 (online)
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Abstract
The reaction of 4-chloro-3-nitrocoumarin with 1,3-bis(silyloxy)buta-1,3-dienes and subsequent reductive cyclization provides a convenient synthesis of a variety of chromeno[3,4-b]pyrrol-4(3H)-ones.
Key words
cyclization - coumarin - heterocycles - silyl enol ethers - pyrroles
-
1a
Kennedy RO.Thorenes RD. Coumarins: Biology, Applications, Mode of Action Wiley; Chichester: 1997. - For reviews, see:
-
1b
Yu DL.Suzuki M.Xie L.Morris-Natschke SL.Lee KH. Med. Res. Rev. 2003, 23: 322 -
1c
Fylaktakidou KC.Hadjipavlou-Litina DJ.Litines KE.Nicolaides DN. Curr. Pharm. Res. 2004, 10: 3813 -
1d
Borges F.Roleira F.Mihazes N.Santana L.Uriarte E. Curr. Med. Chem. 2005, 12: 887 - 2
Chen L.Xu MH. Adv. Synth. Catal. 2009, 351: 2005 ; and references 2-5 cited therein - 3 For a review, see:
Langer P. Synthesis 2002, 441
References and Notes
General Procedure
for the Synthesis of Compounds 5a-k
To a
stirred CH2Cl2 solution (2 mL/1 mmol
of starting materials) of 4-chloro-3-nitrocoumarin 3 (1.0
equiv) and 1,3-bis(silyl enol ethers) 4 (1.1
equiv) was added TiCl4 (1.1 equiv) at -78 ˚C
under an argon atmosphere. The temperature of the reaction mixture
was allowed to rise to 20 ˚C in the period of
12 h. To the solution was added HCl (10%, 20 mL), and the
mixture was extracted with CH2Cl2 (3 Ž 20
mL). The combined organic layers were dried (Na2SO4),
filtered, and the filtrate was concentrated under reduced pressure.
The residue was purified by column chromatography (silica gel, heptanes-EtOAc)
to give 5a-k.
Methyl 4-(3-Nitro-2-oxo-2 H -chromen-4-yl)-3-oxopentanoate (5b) Starting with 3 (0.338 g, 1.5 mmol) and 4b (0.453 g, 1.65 mmol), 5b was isolated by column chromatography (silica gel, heptanes-EtOAc) as a yellow solid (0.324 g, 68%); mp 135-137 ˚C. R f = 0.21 (heptanes-EtOAc, 4:1). ¹H NMR (250 MHz, CDCl3): d = 1.60 (d, ³ J = 7.0 Hz, 3 H, CH3), 3.35 (d, ² J = 16.0 Hz, 1 H, CH2), 3.50 (d, ² J = 16.0 Hz, 1 H, CH2), 3.61 (s, 3 H, OCH3), 4.00 (q, ³ J = 7.0 Hz, 1 H, CH), 7.30-7.42 (m, 2 H, CHAr), 7.51-7.54 (m, 1 H, CHAr), 7.61-7.66 (m, 1 H, CHAr). ¹³C NMR (75 MHz, CDCl3): d = 15.0 (CH3), 47.0 (CH2), 48.2 (CH), 52.7 (OCH3), 115.3 (CAr), 118.3, 126.0, 126.9 (CHAr), 128.0 (CAr), 134.4 (CHAr), 144.3 (CAr), 152.6 (CO), 152.7 (CAr), 166.4, 198.4 (CO). IR (neat): 3117 (w), 3079 (w), 3045 (w), 2992 (w), 2962 (w), 2929 (w), 1732 (s), 1704 (s), 1605 (m), 1536 (s), 1436 (m), 1362 (m), 1323 (m), 1282 (s), 1155 (m), 1070 (m), 1030 (m), 989 (s), 872 (m), 835 (m), 767 (s), 693 (m), 657 (m), 580 (m), 547 (m) cm-¹. ESI-MS: m/z calcd for C15H13NNaO7 [M + Na]+: 342.0584; found: 342.0591. Anal. Calcd for: C15H13NNaO7: 56.43; H, 4.08; N, 4.39. Found: C, 56.94; H, 4.36; N, 4.21.
6
Methyl 4-(3-Nitro-2-oxo-2
H
-chromen-4-yl)-3-oxohexanoate
(5c)
Starting with 3 (0.338
g, 1.5 mmol) and 4c (0.476 g, 1.65 mmol), 5c was isolated by column chromatography
(silica gel, heptanes-EtOAc) as a yellow solid (0.288 g,
58%); mp 99-100 ˚C. R
f
= 0.32 (heptanes-EtOAc, 4:1). ¹H
NMR (250 MHz, CDCl3): δ = 0.86
(t, ³
J = 7.5
Hz, 3 H, CH2CH
3),
1.81-1.97 (m, 1 H, CHCH
2CH3),
2.31-2.45 (m, 1 H, CHCH
2CH3), 3.35
(d, ²
J = 16.1
Hz, 1 H, CH2), 3.54 (d, ²
J = 16.1 Hz,
1 H, CH2), 3.59 (s, 3 H, OCH3), 3.67-3.78
(m, 1 H, CH), 7.28-7.41 (m, 2 H, CHAr), 7.59-7.66
(m, 2 H, CHAr). ¹³C NMR
(75 MHz, CDCl3): δ = 12.1
(CH3), 22.9, 47.4 (CH2), 52.6 (OCH3),
56.0 (CH), 115.5 (CAr), 118.2, 126.0, 127.2 (CHAr), 128.1
(CAr), 134.4 (CHAr), 142.8 (CAr),
152.6 (CO), 152.7 (CAr), 166.4, 198.1 (CO). IR (neat):
2975 (w), 2957 (w), 2923 (w), 2877 (w), 1737 (s), 1719 (s), 1605
(m), 1544 (s), 1436 (m), 1362 (m), 1327 (m), 1245 (s), 1148 (s),
1069 (m), 1047 (m), 994 (m), 899 (m), 837 (m), 774 (m), 755 (s),
656 (s), 590 (m), 561 (m), 533 (m) cm-¹.
ESI-MS: m/z calcd for C16H16NO7 [M + H]+:
334.09213; found: 334.09214. Anal. Calcd for C16H15NO7:
C, 57.66; H, 4.51; N, 4.20. Found: C, 57.52; H, 4.50; N, 4.16.
General Procedure for the Synthesis of Chromeno[3,4- b ]pyrrol-4(3 H )-ones 6a-k In a 50 mL one-neck round Schlenk flask under a flow of dry argon were placed 1.0 mmol of coumpound 5 and 0.05 g of Pd/C (10%). Afterwards, 25 mL of dry degassed MeOH was added. The system was washed three times with H2. The hydrogenation was conducted with the help of a glass burette under atmospheric pressure. After 3 equiv of H2 was consumed, the mixture was stirred for 3 d at 20 ˚C (TLC control). The reaction mixture was filtered through a Celite pad (2-3 cm). The Celite was washed 3 times with MeOH. The solvent of the filtrate was removed under reduced pressure. The residue was purified by preparative chromatography (silica gel, heptanes-EtOAc).
8
Methyl 2-{3,4-Dihydro-1-methyl-4-oxochromeno[3,4-
b
]pyrrol-2-yl}acetate
(6b)
Starting with 5b (0.100
g, 0.31 mmol), 6b was isolated (0.043 g,
51%) by column chromatography (silica gel, heptanes-EtOAc)
as a white solid; mp 211-213 ˚C. R
f
= 0.21 (heptanes-EtOAc, 1:1). ¹H
NMR (250 MHz, CDCl3): δ = 2.36
(s, 3 H, CH3), 3.70 (s, 3 H, OCH3), 3.77 (s,
2 H, CH2), 7.23-7.37 (m, 3 H, CHAr),
7.87-7.90 (m, 1 H, CHAr), 10.26 (s, 1 H, NH). ¹³C
NMR (75 MHz, CDCl3): δ = 11.0 (CH3),
31.3 (CH2), 52.6 (OCH3), 113.5, 116.2 (CAr),
117.5 (CHAr), 119.1 (CAr), 123.3, 124.2, 127.3
(CHAr), 127.5 (CAr), 132.1, 151.3 (CAr),
155.5, 169.9 (CO). IR (neat): 3220 (m), 2953 (w), 2919 (m), 2851
(w), 1730 (m), 1692 (s), 1592 (m), 1504 (m), 1428 (m), 1340 (m),
1276 (s), 1199 (s), 1170 (m), 1147 (s), 1110 (m), 1043 (m), 998
(m), 981 (s), 894 (m), 812 (m), 749 (s), 737 (s), 660 (m), 621 (m),
567 (m), 536 (m). GC-MS (EI, 70 eV): m/z (%) = 271
(60)[M]+, 212 (100), 198 (3),
184 (7), 128 (5). cm-¹. HRMS (EI): m/z calcd for C15H14NO4 [M + H]+:
272.0917; found: 272.0923.
Methyl 2-{1-Ethyl-3,4-dihydro-4-oxochromeno[3,4-
b
]pyrrol-2-yl}acetate
(6c)
Starting with 5c (0.100
g, 0.31 mmol), 6c was isolated (0.060 g,
67%) by column chromatography (silica gel, heptanes-EtOAc)
as a white solid; mp 199-201 ˚C. R
f
= 0.22
(heptanes-EtOAc, 1:1). ¹H
NMR (250 MHz, CDCl3): δ = 1.19
(t, ³
J = 7.5
Hz, 3 H, CH2CH
3),
2.79 (q, ³
J = 7.6
Hz, 2 H, CH
2CH3),
3.68 (s, 3 H, OCH3), 3.78 (s, 2 H, CH2), 7.21-7.38
(m, 3 H, CHAr), 7.82-7.85 (m, 1 H, CHAr),
10.44 (s, 1 H, NH). ¹³C NMR (75 MHz,
CDCl3): δ = 14.8
(CH3), 18.3, 31.3 (CH2), 52.6 (OCH3),
116.3 (CAr), 117.6 (CHAr), 118.8, 120.4 (CAr),
123.3, 124.3 (CHAr), 126.8 (CAr), 127.3 (CHAr), 132.0,
151.2 (CAr), 155.6, 170.0 (CO). IR (neat): 3218 (w), 2966
(w), 2951 (w), 2931 (w), 2875 (w), 1738 (m), 1681 (s), 1674 (s),
1610 (m), 1555 (m), 1456 (m), 1424 (m), 1301 (m), 1253 (m), 1230
(m), 1148 (s), 1114 (m), 1013 (s), 984 (s), 850 (m), 739 (s), 713
(s), 659 (m), 631 (s), 586 (m), 546 (w) cm-¹.
GC-MS (EI, 70 eV): m/z (%) = 285
(100) [M]+, 270 (39), 238
(7), 226 (82), 212 (42), 182 (8), 167 (10). HRMS (EI): m/z calcd for C16H16NO4 [M + H]+:
286.1074; found: 286.1076.