Conversion of Acetates of Baylis-Hillman Adducts
J . Org. Chem., Vol. 64, No. 4, 1999 1199
of the corresponding Baylis-Hillman adducts with acetyl
chloride in the presence of pyridine at room temperature.
Meth yl 3-Hyd r oxy-2-m eth ylen e-3-(4-(tetr a d ecyloxy)-
p h en yl)p r op a n oa te (8). A mixture of 4-(tetradecyloxy)-
benzaldehyde (3.18 g, 10 mM), methyl acrylate (1.72 g, 20
mM), and DABCO (0.224 g, 2 mM) was allowed to stand at
room temperature for 20 days. The reaction mixture was
diluted with ether, washed successively with 2 N hydrochloric
acid, water, and a saturated aqueous sodium bicarbonate
solution, and dried over anhydrous Na2SO4. Evaporation of
the solvent followed by silica gel column chromatography (5%
EtOAc in hexanes) provided 8 as white solid.: yield 1.14 g (71%
based on 1.92 g of the recovered p-(tetradecyloxy)benzaldehyde,
i.e., 40% reaction); mp 72 °C; 1H NMR δ 0.89 (dist. t, 3H),
1.15-1.88 (m, 24H), 2.86 (d, 1H, J ) 5.2 Hz), 3.72 (s, 3H),
3.94 (t, 2H, J ) 6.6 Hz), 5.53 (d, 1H, J ) 5.0 Hz), 5.85 (s, 1H),
6.32 (s, 1H), 6.87 (d, 2H, J ) 8.2 Hz), 7.28 (d, 2H, J ) 8.2 Hz);
13C NMR δ 14.07, 22.69, 26.11, 29.37, 29.69, 31.95, 51.77,
68.14, 72.72, 114.52, 125.25, 127.92, 133.49, 142.59, 158.94,
g) in methanol (5 mL) at room temperature for 2 h. The
methanol was removed under reduced pressure, the residue
was diluted with water, acidified with dilute HCl, and ex-
tracted with ether, and the combined organic layer was dried
over anhydrous Na2SO4. Solvent was evaporated, and the
crude acid obtained was crystallized from ethyl acetate and
hexanes (1:1) to provide the acid 7a as colorless crystals: yield
0.599 g (74%); mp 81-83 °C {lit.10 mp 80-81 °C }; 1H NMR δ
2.14 (s, 3H), 7.25-7.62 (m, 5H), 7.83 (s, 1H), 11.35 (b, 1H);
13C NMR δ 13.70, 127.68, 128.47, 128.72, 129.88, 135.67,
141.17, 174.61; IR (KBr) 3350-2660, 1666, 1620 cm-1. Anal.
Calcd for C10H10O2: C, 74.05; H, 6.21. Found: C, 73.85; H,
6.21.
P r oced u r e B (P r oced u r e for On e-P ot Syn t h esis of
7a ). To a stirred solution of 5a (1.17 g, 5 mM) in tert-butyl
alcohol (5 mL) was added NaBH4 (0.19 g, 5 mM) at room
temperature. After 15 min, 85% KOH (1.00 g) in methanol (5
mL) was added and the stirring was continued for 2 h at room
temperature. Usual workup (as mentioned above) followed by
crystallization from ethyl acetate and hexanes (1:1) afforded
the pure acid 7a as colorless crystals: yield 0.615 g (76%).
166.80; IR (KBr) 3364, 1724 cm-1
.
ter t-Bu tyl 3-Hyd r oxy-2-m eth ylen e-3-(4-(m eth oxyca r -
bon yl)p h en yl)p r op a n oa te (9). This compound was prepared
from 4-(methoxycarbonyl)benzaldehyde (1.64 g, 10 mM) and
tert-butyl acrylate (1.538 g, 12 mM) in the presence of DABCO
(0.224 g, 2 mM) by following a procedure similar to that of 8.
Compounds 7b-f and 3 were synthesized according to both
the procedures A and B and the yields were comparable.
[E]-2-Meth yl-3-(4-m eth ylph en yl)pr op-2-en oic Acid (7b):
yield 72%; mp 165-167 °C {lit.10 mp 168-169 °C}; 1H NMR δ
2.16 (s, 3H), 2.39 (s, 3H), 7.23 (d, 2H, J ) 7.6 Hz), 7.36 (d, 2H,
J ) 7.6 Hz), 7.81(s, 1H); 13C NMR δ 13.75, 21.35, 126.62,
129.19, 129.96, 132.81, 138.94, 141.13, 174.28; IR (KBr) 3350-
2600, 1667, 1630 cm-1. Anal. Calcd for C11H12O2: C, 74.97; H,
6.86. Found: C, 74.62; H, 6.89.
1
9: reaction time 7 days; yield 2.10 g (72%); mp 68-70 °C; H
NMR δ 1.40 (s, 9H), 3.28 (m, 1H), 3.91 (s, 3H), 5.53 (d, 1H, J
) 6.2 Hz), 5.71 (s, 1H), 6.27 (s, 1H), 7.45 (d, 2H, J ) 8.0 Hz),
8.02 (d, 2H, J ) 8.0 Hz); 13C NMR δ 27.91, 52.03, 73.05, 81.84,
125.61, 126.51, 129.34, 129.60, 143.02, 146.93, 165.37, 166.92;
IR (KBr) 3304, 1716 cm-1
.
[E]-3-(4-Ch lor op h en yl)-2-m et h ylp r op -2-en oic
Acid
Met h yl 3-Acet oxy-2-m et h ylen e-3-(4-(t et r a d ecyloxy)-
p h en yl)p r op a n oa te (5g). To a solution of 8 (0.808 g, 2 mM)
and pyridine (0.316 g, 4 mM) in dry dichloromethane at 0 °C
was added acetyl chloride (0.314 g, 4 mM) slowly, and the
solution was stirred at room temperature for 1 h. The reaction
mixture was taken up in ether and washed successively with
a 2 N HCl solution, water, and a saturated aqueous NaHCO3
solution. The organic layer was dried over anhydrous Na2SO4.
Evaporation of the solvent followed by silica gel column
chromatography (2% EtOAc in hexanes) provided the pure
acetate 5g: yield 0.788 g (88%); mp 59 °C; 1H NMR δ 0.88
(dist. t, 3H), 1.12-1.87 (m, 24H), 2.09 (s, 3H), 3.70 (s, 3H),
3.93 (t, 2H, J ) 6.7 Hz), 5.87 (s, 1H), 6.37 (s, 1H), 6.63 (s, 1H),
6.85 (d, 2H, J ) 8.6 Hz), 7.28 (d, 2H, J ) 8.6 Hz); 13C NMR δ
14.07, 21.04, 22.67, 26.06, 29.37, 29.66, 31.92, 51.85, 68.00,
72.91, 114.42, 124.97, 129.09, 129.64, 139.96, 159.29, 165.44,
(7c): yield 73%; mp 168-169 °C {lit.10 mp 166-167 °C}; H
NMR δ 2.12 (d, 3H, J ) 1.4 Hz), 7.24-7.50 (m, 4H), 7.76 (s,
1H); 13C NMR δ 13.81, 128.24, 128.84, 131.15, 134.10, 134.82,
139.80, 173.69; IR (KBr) 3300-2600, 1672, 1625 cm-1. Anal.
Calcd for C10H9ClO2: C, 61.08; H, 4.61. Found: C, 61.42; H,
4.59.
1
[E]-2-Meth yl-3-(4-isop r op ylp h en yl)p r op -2-en oic Acid
(7d ): yield 70%; mp 89-90 °C {lit.10 mp 89-90 °C}; 1H NMR
δ 1.27 (d, 6H, J ) 6.8 Hz), 2.16 (s, 3H), 2.92 (m, 1H), 7.27 (d,
2H, J ) 8.0 Hz), 7.39 (d, 2H, J ) 8.0 Hz), 7.81(s, 1H); 13C NMR
δ 13.76, 23.82, 34.03, 126.58, 126.71, 130.15, 133.23, 141.18,
149.85, 174.72; IR (KBr) 3260-2650, 1678, 1622 cm-1. Anal.
Calcd for C13H16O2: C, 76.43; H, 7.89. Found: C, 76.85; H,
7.92.
[E]-3-(2,4-Dich lor op h en yl)-2-m eth ylp r op -2-en oic Acid
169.32; IR (KBr) 1741, 1716 cm-1
.
1
(7e): yield 75%; mp 143 °C {lit.10 mp 146-147 °C}; H NMR
ter t-Bu tyl 3-Acetoxy-2-m eth ylen e-3-(4-(m eth oxyca r bo-
n yl)p h en yl)p r op a n oa te (5h ). This compound was obtained
as a viscous liquid by the reaction of tert-butyl 3-hydroxy-2-
methylene-3-(4-(methoxycarbonyl)phenyl)propanoate (9) (1.46
g, 5 mM) with acetyl chloride (0.785 g, 10 mM) in the presence
of pyridine (0.95 g, 12 mM) in dichlormethane following a
procedure similar to that of 5g. 5h : yield 1.58 g (95%); 1H
NMR δ 1.37 (s, 9H), 2.11 (s, 3H), 3.91 (s, 3H), 5.76 (s, 1H),
6.35 (s, 1H), 6.68 (s, 1H), 7.44 (d, 2H, J ) 8.4 Hz), 8.01 (d, 2H,
J ) 8.0 Hz); 13C NMR δ 20.95, 27.85, 52.06, 72.80, 81.66,
125.34, 127.66, 129.64, 129.99, 140.59, 143.12, 163.86, 166.62,
δ 2.01 (d, 3H, J ) 1.5 Hz), 7.29 (m, 2H), 7.47 (s, 1H), 7.85 (s,
1H); 13C NMR δ 13.80, 127.02, 129.76, 130.43, 131.20, 132.76,
135.18, 137.08, 173.44; IR (KBr) 3350-2600, 1703, 1635 cm-1
.
Anal. Calcd for C10H8Cl2O2: C, 51.98; H, 3.49. Found: C, 51.62;
H, 3.48.
[E]-3-(Naph th -1-yl)-2-m eth ylpr op-2-en oic Acid (7f): yield
74%; mp 153 °C {lit.10 mp 155-156°C}; 1H NMR δ 1.97 (d, 3H,
J ) 1.5 Hz), 7.31-8.00 (m, 7H), 8.31 (s, 1H); 13C NMR δ 14.01,
124.66, 125.17, 126.25, 126.57, 126.81, 128.64, 128.99, 129.97,
131.58, 132.87, 133.58, 139.83, 174.10; IR (KBr) 3200-2650,
1684, 1618 cm-1. Anal. Calcd for C14H12O2: C, 79.22; H, 5.69.
Found: C, 78.92; H, 5.70.
169.25; IR (neat) 1740, 1724 cm-1
.
[E]-2-Meth yl-3-p h en ylp r op -2-en oic Acid (7a ) (P r oce-
d u r e A). To a solution of methyl 3-acetoxy-2-methylene-3-
phenylpropanoate (5a ) (1.17 g, 5 mM) in anhydrous tert-butyl
alcohol (5 mL) was added NaBH4 (0.19 g, 5 mM), and the
solution was stirred at room temperature for 15 min. tert-Butyl
alcohol was distilled off under reduced pressure, and the
residue was diluted with water and extracted with ether. The
ether layer was dried over anhydrous Na2SO4 and concen-
trated.8 The crude product was treated with 85% KOH (1.00
[E]-3-(4-(Tet r a d ecyloxy)p h en yl)-2-m et h ylp r op -2-en o-
ic Acid (3). This reaction was carried out on a 1 mM scale on
the acetate 5g with 1 mM of NaBH4. 3: yield 75%; mp 90 °C
1
{lit.1 mp 90-91 °C}; H NMR δ 0.87 (dist. t, 3H), 1.13-1.88
(m, 24H), 2.17 (s, 3H), 4.00 (t, 2H, J ) 6.5 Hz), 6.93 (d, 2H, J
) 8.2 Hz), 7.41 (d, 2H, J ) 8.2 Hz), 7.78 (s, 1H); 13C NMR δ
13.83, 14.17, 22.77, 26.13, 29.32, 29.46, 29.76, 32.02, 68.25,
114.62, 125.10, 128.15, 131.84, 140.99, 159.80, 174.49; IR
(CHCl3) 3610-2640, 1682, 1602 cm-1; MS m/z 374 (M+). Anal.
Calcd for C24H38O3: C, 76.96; H, 10.23. Found: C, 77.00; H,
10.25.
[E]-3-(4-(Met h oxyca r b on yl)p h en yl)-2-m et h ylp r op -2-
en oic Acid (4). A solution of crude tert-butyl 2-methyl-3-(4-
(methoxycarbonyl)phenyl)prop-2-enoate (6h ) [obtained by the
(9) The 1H NMR spectrum of the crude products (6a -f) indicated
the presence of 2-7% [Z]-isomer.
(10) Gensler, W. J .; Berman, E. J . Am. Chem. Soc. 1958, 80, 4949.
(11) Hoffmann, H. M. R.; Rabe, J . Angew. Chem., Int. Ed. Engl.
1983, 22, 795.