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DOI: 10.1055/s-0029-1219574
First InCl3-Catalyzed, Three-Component Coupling of Aldehydes, β-Naphthol, and 6-Amino-1,3-dimethyluracil to Functionalized Naphthopyranopyrimidines
Publication History
Publication Date:
05 March 2010 (online)
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Abstract
Indium(III) chloride was found to be a highly effective and efficient catalyst for the three-component, one-pot coupling of aldehydes, β-naphthol, and 6-amino-1,3-dimethyluracil under solvent-free conditions to give 8,10-dimethyl-12-aryl-12H-naphtho[1′,2′:5,6]pyrano[2,3-d]pyrimidine-9,11-diones in high yields for the first time. No co-catalyst or activator is required. Water and ammonia are the only byproducts in the reactions.
Key words
multicomponent reaction - one-pot synthesis - InCl3 - naphthopyranopyrimidine
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References and Notes
General Procedure
for Synthesis of 8,12-Dihydro-8,10-dimethyl-12-aryl-9
H
-naphtho[1′,2′:5,6]pyrano[2,3-
d
]pyrimidine-9,11-(10
H
)-dione (4)
The
aldehyde (1.0 mmol), 6-amino-1,3-dimethyluracil (1.2 mmol), and
2-naphthol (1.0 mmol) were ground in a mortar. The catalyst InCl3 (35
mol%) was added to the reaction mixture and further ground
nicely for additional 15 min. The whole reaction mixture was heated
in an oil bath at 120 ˚C for the stipulated period
of time (Table
[¹]
)
till the completion of the reaction (monitored by TLC). Water (50
mL) was added to the reaction mixture to remove unreacted reactants, and
the product was extracted with EtOAc (3 × 20
mL). The organic layer was dried over anhyd MgSO4, and
the solvent was evaporated under vacuum. The residue obtained was purified
by column chromatography on silica gel using EtOAc-n-hexane (1:4) to afford the pure desired
product. Finally the products were recrystallized from MeOH.
Spectral and Analytical Data of Some Newly Synthesized Compounds
12-(4-Methoxyphenyl)-8,12-dihydro-8,10-dimethyl-9
H
-naphtho[1′,2′:5,6]pyrano[2,3-
d
]pyrimidine-9,11-(10
H
)-dione (4d)
White
solid; R
f
= 0.40 (EtOAc-hexane,
1:4); mp 257-258 ˚C. IR (KBr): 3057,
2948, 1708, 1650, 1587, 1481
cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 8.03-7.93
(m, 3 H), 7.61-7.43 (m, 3 H), 7.24 (d, J = 7.8
Hz, 2 H), 6.74 (d, J = 7.8
Hz, 2 H), 5.61 (s, 1 H), 3.62 (s, 3 H), 3.50 (s, 3 H), 3.16 (s,
3 H). ¹³C NMR (75 MHz, DMSO-d
6): δ = 161.4, 157.7,
151.8, 150.1, 146.6, 135.9, 131.3, 130.3, 129.1, 128.9, 128.2, 127.0,
125.1, 123.4, 117.0, 116.3, 113.3, 90.9, 54.7, 34.7, 28.7, 27.7.
MS-FAB: m/z = 401 [M + H]+.
Anal. Calcd for C24H20N2O4:
C, 71.99; H, 5.03; N, 7.00. Found: C, 71.78; H, 4.91; N, 6.88.
12-(3-Hydroxyphenyl)-8,12-dihydro-8,10-dimethyl-9
H
-naphtho[1′,2′:5,6]pyrano[2,3-
d
]pyrimidine-9,11-(10
H
)-dione (4m)
White
solid; R
f
= 0.40 (EtOAc-hexane,
2:5); mp 293-294 ˚C. IR (KBr): 3409,
3054, 2951, 1708, 1642, 1590, 1478 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 7.95-7.82
(m, 3 H), 7.43-7.37 (m, 3 H), 7.09 (t, J = 8.1
Hz, 1 H), 6.90-6.88 (m, 2 H), 6.60 (d, J = 7.2
Hz, 1 H), 5.77 (s, 1 H), 5.23 (s, 1 H), 3.60 (s, 3 H), 3.33 (s,
3 H). ¹³C NMR (75 MHz, CDCl3): δ = 161.9,
155.6, 152.4, 150.6, 147.2, 145.5, 131.7, 130.9, 129.6, 129.5, 128.4,
127.5, 125.5, 123.9, 120.5, 116.2, 115.3, 113.9, 106.8, 91.3, 35.7,
29.0, 28.2. MS-FAB:
m/z = 387 [M + H]+.
Anal. Calcd for C23H18N2O4:
C, 71.49; H, 4.70; N, 7.25. Found: C, 71.41; H, 4.67; N, 7.12.
12-(5-Bromo-2-hydroxyphenyl)-8,12-dihydro-8,10-dimethyl-9
H
-naphtho[1′,2′:5,6]pyrano[2,3-
d
]pyrimidine-9,11-(10
H
)-dione (4o)
White
solid; R
f
= 0.40 (EtOAc-hexane,
2:3); mp 291-292 ˚C. IR (KBr): 3112,
2951, 2930, 1703, 1643, 1591, 1476 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 9.18
(s, 1 H), 8.25-8.03 (m, 4 H), 7.83-7.77 (m, 2
H), 7.65-7.45 (m, 3 H) 6.55 (s, 1 H), 3.68 (s, 3 H), 3.35
(s, 3 H). ¹³C NMR (75 MHz, DMSO-d
6): δ = 161.1,
153.8, 152.7, 150.0, 146.8, 132.9, 132.6, 131.1, 130.5, 130.3, 129.3,
128.5, 127.2, 125.2, 123.5, 118.1, 116.8, 116.3, 110.1, 88.6, 30.7,
28.9, 27.7. MS-FAB: m/z = 465 [M + H]+.
Anal. Calcd for C23H17BrN2O4:
C, 59.37; H, 3.68; N, 6.02. Found: C, 59.19; H, 3.58; N, 5.91.
12-(2-Hydroxy-5-nitrophenyl)-8,12-dihydro-8,10-dimethyl-9
H
-naphtho[1′,2′:5,6]pyrano[2,3-
d
]pyrimidine-9,11-(10
H
)-dione (4p)
Yellow
solid; R
f
= 0.40 (EtOAc-hexane,
2:3); mp 215-217 ˚C. IR (KBr): 3320,
2951, 2930, 1709, 1646, 1586, 1470 cm-¹. ¹H
NMR (300 MHz, DMSO-d
6): δ = 9.66
(s, 1 H), 8.16-8.09 (m, 2 H), 7.97-7.31 (m, 5
H), 6.91-6.88 (m, 2 H), 6.10 (s, 1 H), 3.50 (s, 3 H), 3.02
(s, 3 H). ¹³C NMR (75 MHz, DMSO-d
6): δ = 161.2,
153.9, 152.7, 150.2, 147.3, 133.1, 131.4, 129.8, 129.2, 128.4, 127.6,
125.9, 125.5, 123.4, 122.8, 122.3, 118.9, 117.3, 116.4, 87.6, 29.6,
29.2, 27.7. MS-FAB: m/z = 432 [M + H]+.
Anal. Calcd for C23H17N3O6: C,
64.04; H, 3.97; N, 9.74. Found: C, 63.91; H, 3.85; N, 9.72.
12-(3-Ethoxy-2-hydroxyphenyl)-8,12-dihydro-8,10-dimethyl-9
H
-naphtho[1′,2′:5,6]pyrano[2,3-
d
]pyrimidine-9,11-(10
H
)-dione (4r)
White
solid; R
f
= 0.40 (EtOAc-hexane,
3:7); mp 208-209 ˚C. IR (KBr): 3225,
3061, 2963, 2928, 1702, 1671, 1590, 1482 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 9.41
(s, 1 H), 7.69-7.67 (m, 2 H), 7.46-7.15 (m, 4
H), 6.87 (t, J = 7.8 Hz,
1 H), 6.77 (d, J = 8.1
Hz, 1 H), 6.42 (d, J = 7.5
Hz, 1 H), 6.03 (s, 1 H), 4.21-4.10 (m, 2 H), 3.68 (s, 3
H), 3.30 (s, 3 H), 1.56 (t, J = 6.9
Hz, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 162.1,
153.4, 153.1, 150.1, 147.4, 139.1, 132.0, 130.1, 129.6, 129.0, 126.1,
125.9, 125.4, 123.2, 123.0, 122.4, 122.1, 111.2, 90.2, 52.1, 31.0,
28.9, 27.7, 14.8. MS-FAB:
m/z = 431 [M + H]+.
Anal. Calcd for C25H22N2O5:
C, 69.76; H, 5.15; N, 6.51. Found: C, 69.69; H, 4.92; N, 6.32.