Selective Route to Coumalate Derivatives
mated from the peak areas, based on the GC internal standard
technique. The solvent was removed under reduced pressure, and
the residue was neutralized with sodium hydrogen carbonate and
then extracted with ethyl acetate (50 mL). Product 7 was isolated
by column chromatography (SiO2; hexane/ethyl acetate, 5:1) in 89%
yield [121 mg; Equation (4)].
Conclusions
We have developed a novel selective route to coumalate
derivatives and 1,3,5-triacetylbenzene from easily available
acetals by choosing either d-block Lewis acids or lantha-
nide chlorides.
1
Compound 6b: Yield: 87% (317 mg). H NMR (270 MHz, CDCl3):
δ = 7.70 (d, J = 10 Hz, 1 H, 5-H), 6.04 (d, J = 10 Hz, 1 H, 6-H),
4.18 (q, J = 7 Hz, 2 H, -CO2-CH2-CH3), 2.52 (s, 3 H, -CH3), 1.23
(t, J = 7 Hz, 3 H, -CO2-CH2-CH3) ppm. 13C NMR (67.5 MHz,
CDCl3): δ = 13.86 (CH3), 20.05 (CH3), 61.03 (CH2), 108.83 (C),
111.75 (CH), 143.60 (CH), 160.09 (C), 163.48 (C), 170.65 (C) ppm.
Experimental Section
General: All starting materials were commercially available and
used
without
any
purification.
Heteropolyacid
(H4PMo11VO40·13H2O) was prepared according to a literature pro-
cedure.[13] Compounds 2,[6] 3,[7] 6a,[14] and 7[10a] were reported pre-
viously.
IR (neat): ν = 778, 852, 1017, 1084, 1175, 1317, 1553, 1628, 1735,
˜
2979 cm–1. GC–MS (EI): m/z (%) = 182 (89) [M]+, 137 (74), 126
(81), 43 (100). C9H10O4 (182.18): calcd. C 59.34, H 5.53; found C
59.07, H 5.81.
Typical Reaction Procedure for the Formation of Ethyl Coumalate:
FeCl3·6H2O (81 mg, 0.30 mmol, 15 mol-%) was added to 1a
(380 mg, 2 mmol) in a mixed solvent of ethanol (1 mL) and acetic
acid (8 mL) in open air. The reaction mixture was stirred at 90 °C
for 6 h. After the reaction was complete, GC and GC–MS analyses
were performed. The conversions and yields of products were esti-
mated from the peak areas, based on the GC internal standard
technique. The solvent was removed under reduced pressure, the
residue was neutralized with sodium hydrogen carbonate and then
extracted with ethyl acetate (50 mL). Product 2 was isolated by col-
umn chromatography (SiO2; hexane/ethyl acetate, 5:1) in 88% yield
(148 mg; Table 1, Entry 1).
Compound 6c: Yield: 85% (334 mg). M.p. 49–50 °C. 1H NMR
(270 MHz, CDCl3): δ = 7.81 (d, J = 10 Hz, 1 H, 5-H), 6.17 (d, J
= 10 Hz, 1 H, 6-H), 4.30 (q, J = 7 Hz, 2 H, -CO2-CH2-CH3), 3.03
(q, J = 7 Hz, 2 H, -CH2-CH3), 1.35 (t, J = 7 Hz, 3 H, -CH3), 1.27
(t, J = 7 Hz, 3 H, -CH3) ppm. 13C NMR (67.5 MHz, CDCl3): δ =
11.63 (CH3), 14.03 (CH3), 26.69 (CH2), 61.37 (CH2), 108.37 (C),
112.02 (CH), 144.06 (CH), 160.72 (C), 163.71 (C), 175.35 (C) ppm.
IR (neat): ν = 774, 1050, 1095, 1186, 1272, 1618, 1712, 1774, 2976,
˜
3107 cm–1. GC–MS (EI): m/z (%) = 196 (38) [M]+, 168 (20), 150
(59), 139 (100). HRMS (EI): calcd. for C10H12O4 196.0736; found
196.0732.
One-Pot Synthesis of Ethyl Coumalate (2) from Ethyl Acrylate (4)
Compound 6d: Yield: 57% (173 mg). M.p. 62–64 °C. 1H NMR
(270 MHz, CDCl3): δ = 7.66 (d, J = 10 Hz, 1 H, 5-H), 6.16 (d, J
= 10 Hz, 1 H, 6-H), 2.55 (s, 3 H, -CH3), 2.40 (s, 3 H, -CO2-CH3)
ppm. 13C NMR (67.5 MHz, CDCl3): δ = 20.85 (CH3), 29.21 (CH3),
112.12 (CH), 116.16 (C), 143.22 (CH), 160.10 (C), 170.42 (C),
in the Presence of Pd(OAc)2/HPMoV/FeCl3:
A mixture of
Pd(OAc)2 (22 mg, 0.1 mmol, 5 mol-%), H4PMo11VO40·13H2O
(HPMo11V; 35 mg, 17 µmol, 0.85 mol-%) and FeCl3·6H2O (81 mg,
0.30 mmol, 15 mol-%) was added to ethyl acrylate (200 mg,
2 mmol) in a mixed solvent of ethanol (1 mL) and acetic acid
(8 mL) under an atmosphere of O2 (1 atm). The reaction mixture
was stirred at 90 °C for 6 h. The conversions and yields of products
were estimated from the peak areas, based on the GC internal stan-
dard technique. The solvent was removed under reduced pressure,
and the residue was neutralized with sodium hydrogen carbonate
and then extracted with ethyl acetate (50 mL). Product 2 was iso-
lated by column chromatography (SiO2; hexane/ethyl acetate, 5:1)
in 65% yield [109 mg; Equation (2)].
194.83 (C) ppm. IR (neat): ν = 581, 951, 1202, 1297, 1363, 1605,
˜
1684, 1737, 3078, 2918 cm–1. GC–MS (EI): m/z (%) = 152 (78)
[M]+, 137 (48), 109 (100), 95 (83). HRMS (EI): calcd. for C8H8O3
152.0473; found 152.0478.
1
Compound 6e: Yield: 65% (234 mg). H NMR (270 MHz, CDCl3):
δ = 7.67 (d, J = 10 Hz, 1 H, 5-H), 6.14 (d, J = 10 Hz, 1 H, 6-H),
2.86 (q, J = 7 Hz, 2 H, -CO-CH2-CH3), 2.71 (q, J = 7 Hz, 2 H, -
CH2-CH3), 1.21 (t, J = 7 Hz, 3 H, -CO-CH2-CH3), 1.09 (t, J =
7 Hz, 3 H, -CH2-CH3) ppm. 13C NMR (67.5 MHz, CDCl3): δ =
7.68 (CH3), 11.41 (CH3), 26.57 (CH2), 34.06 (CH2), 111.91 (CH),
115.22 (C), 142.79 (CH), 160.13 (C), 173.91 (C), 197.75 (C) ppm.
Reaction of Ethyl 3,3-Diethoxypropionate (1a) with Methyl Aceto-
acetic Acid (5a) in the Presence FeCl3: To a solution of FeCl3·6H2O
(81 mg, 0.30 mmol, 15 mol-%) and 5a (1160 mg, 10 mmol) in a
mixed solvent of ethanol (0.5 mL) and acetic acid (8 mL) was
added a solution of 1a (380 mg, 2 mmol) in ethanol (0.5 mL) over
a period of 3 h by using a syringe pump in open air, and the mix-
ture was stirred at 90 °C for an additional 12 h. After the reaction
was complete, GC and GC–MS analyses were performed. The con-
versions and yields of products were estimated from the peak areas,
based on the GC internal standard technique. The solvent was re-
moved under reduced pressure, and the residue was neutralized
with sodium hydrogen carbonate and then extracted with ethyl ace-
tate (50 mL). Product 6a was isolated by Kugelrohr distillation and
column chromatography (SiO2; hexane/ethyl acetate, 5:1) in 95%
yield (319 mg; Table 2, Entry 2).
IR (neat): ν = 807, 938, 1058, 1215, 1455, 1542, 1612, 1746, 2937,
˜
2980 cm–1. GC–MS (EI): m/z (%) = 180 (42) [M]+, 151 (100), 95
(66), 57 (36). HRMS (EI): calcd. for C10H12O3180.0786; found
180.0789.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures and 1H and 13C NMR spectroscopic
data for 2, 3, 5, 6, and 7.
Acknowledgments
Reaction of 4,4-Dimethoxy-2-butanone (1b) in the Presence of AlCl3:
AlCl3 (45 mg, 0.3 mmol, 15 mol-%) was added to 1b (264 mg,
2 mmol) in a mixed solvent of ethanol (1 mL) and acetic acid
(8 mL) in open air. The reaction mixture was stirred at 60 °C for
15 h. After the reaction was complete, GC and GC–MS analyses
were performed. The conversions and yields of products were esti-
This work was supported by a Grant-in-Aid for Scientific Research
on Priority Areas “Advanced Molecular Transformation of Carbon
Resources” from the Ministry of Education, Culture, Sports, Sci-
ence and Technology, Japan, “High-Tech Research Center” Project
for Private Universities: matching fund subsidy from the Ministry
of Education, Culture, Sports, Science and Technology, 2005–2009.
Eur. J. Org. Chem. 2009, 4067–4072
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4071