Notes
J . Org. Chem., Vol. 62, No. 5, 1997 1551
Ta ble 1. Cop p er -Dia m in e-Ca ta lyzed Rea ction of 4-Meth oxystyr en e (2) w ith Ca r bon Tetr a ch lor id e
ratio (%)b
2
CCl4
(mol)
Cu(I) Cl
mol
time
(h)
conversion
(%)
total (3 +4)
yield (%)
a
entry
(mol)
diamine (mol)
3
4
1
2
3
4
5
6
0.13
0.065
0.13
0.065
0.05
0.065
0.49
0.25
0.49
0.25
0.16
0.25
0.0045
0.0045
0.0045
0.0023
0.008
TMEDA (0.014)
TMPDA (0.014)
TMBDA (0.014)
2,2-Bipy(0.014)
pyridine(0.016)
TMPDA(0.014)
1.5
2.0
3.0
5.5
6.0
2.0
99.6
99.5
23.0
11.0
54.0
100.0
73
82
9
1
19
70
13
13
3
1
7
86
95
12
2
26
94
c
0.0045
24
a
TMEDA ) N,N,N′,N′-Tetramethyl-1,2-ethylenediamine; TMPDA ) N,N,N′,N′-Tetramethyl-1,3-propanediamine; TMBDA ) N,N,N′,N′-
Tetramethyl-1,4-butanediamine, 2,2-bipypridyl. Yields were calculated by GC using response factor analysis. c CuCl2 was used in this
b
reaction.
Reaction of a mixture of 3 and 4 with 2 equiv of
-ethylhexyl alcohol (EHA) in the presence of a catalytic
amount of p-toluenesulfonic acid (p-TsOH) afforded 1 in
0% yield. Purification via distillation afforded pure 1
in 57% yield. In another experiment, the hydrolysis and
esterification of a mixture of 3 and 4 was repeated in the
absence of p-TsOH. In this experiment, 1 was isolated
in 61% yield. In a one-pot reaction avoiding isolation of
intermediate coupling products (3 and 4), 1 was isolated
in 58% yield.
hydrogenation and dehydration. 4-Methoxycinnamic acid was
purchased from Aldrich Chemical Co.
2
2
-Eth ylh exyl 4-Meth oxycin n a m a te (1) fr om 2. A solution
of 2 (17.4 g, 0.13 mol), CCl
(75 g, 0.49 mol), Cu(I)Cl (0.9 g, 0.009
mol), and TMPDA (3.5 g, 0.027 mol) was stirred at reflux for
4
.5 h. The reaction mixture was then filtered, washed with CCl ,
4
6
3
and concentrated in vacuo (∼5 mm Hg, 25 °C). The resulting
amine-free mixture of 3 and 4 was then added to 2-ethyl-1-
hexanol (33.8 g, 0.26 mol), water (2.3 g, 0.13 mol), and p-
toluenesulfonic acid (0.26 g, 0.0013 mol) and stirred at 120 °C
for 1 h. GC response factor analysis of a sample of the reaction
mixture indicated an overall yield of 64%. Vacuum distillation
afforded pure 1 (38.0 g, 62% yield); bp 160 °C at 0.05 mm of Hg;
Attempted purification of a mixture containing 3 and
, via vacuum distillation at 130-200 °C, led to complete
4
9
1
lit. bp 185-195 °C at 1.0 mmHg. H NMR δ: 7.64 (d, 1 H, J )
conversion of 3 to 4, compound 4 being the only volatile
product collected. The reaction of 4 with EHA in the
presence of 1 equiv of water and catalytic amount of
p-TsOH afforded 1 in 80% yield.
Hydrolysis of a mixture of 3 and 4 in acetic acid, in
the presence of p-TsOH, proceeded with complete conver-
sion and afforded 4-methoxycinnamic acid in only 15%
yield.
16 Hz), 7.19 (AA’BB’ quartet, 4 H, aromatic), 6.32 (d, 1H, J )
1
3
16 Hz), 4.11 (d, 2 H), 3.83 (s, 3 H), 1.41-0.87 (m, 15 H);
C
NMR δ: 167.6, 161.5, 144.2, 129.7, 127.4, 116.0, 114.4, 66.8, 55.3,
3
8.9, 30.4, 28.9, 23.8, 22.8, 13.8, 10.9 ppm. The product was
identical to an authentic sample of 1 made via esterification of
commercial 4-methoxycinnamic acid with 2-ethylhexanol.
1
,1,1,-Tr ich lor o-3-(4′-m eth oxyp h en yl)-2-p r op en e (4). A
reaction mixture containing 3 (69.8 wt %) and 4 (23.7 wt %) was
placed in a flask equipped with a simple distillation setup. The
mixture was heated to 200 °C, and 4 was distilled, bp 130 °C at
1
,1,1,3-Tetr a ch lor o-3-(4′-a cetoxyp h en yl)p r op a n e
7). We have also evaluated copper/diamine-catalyzed
addition of CCl
to 4-acetoxystyrene (6) in the presence
0
%
.5 mmHg. GC analysis of the distillate showed it to be 83 wt
(
1
pure. H NMR δ: 7.15 (AA’BB’ quartet, 4 H, aromatic), 6.37
4
13
(
d, 1H, J ) 10 Hz), 5.74 (d,1 H, J ) 10 Hz), 3.82 (s, 3H);
C
of catalytic amount of TMEDA. The corresponding
addition product, 1,1,1,3-tetrachloro-3-(4′-acetoxyphenyl)-
propane (7), was isolated in 93% yield. Surprisingly,
formation of HCl elimination product, i.e., 1,1,1-trichloro-
NMR δ: 160.2, 130.8, 129.7, 128.4, 123.9, 114.5, 58.3, 55.3 ppm;
IR νmax: 2833 (m), 1607 (vs), 1509 (vs), 1460 (s), 1252 (vs), 1030
-
1
(vs), 826 (vs) and 625 (vs) cm . MS: (mlz, relative intensity)
+
2
1
50 (M , 12), 215 (100), 213 (42), 179 (55), 177 (22), 145 (20),
01 (15).
3
-(4′-acetoxyphenyl)-2-propene was not observed in this
Syn th esis of 1 fr om 4. A distilled sample of 4 (10 g, 0.04
reaction. The reaction of 7 with ethyl alcohol led to the
formation of ethyl 4-hydroxycinnamate (10) along with
some decomposition products. The acetate group of
compound 7 underwent complete hydrolysis during this
transformation.
mol), 2-ethyl-1-hexanol (10.4 g, 0.08 mol), water (0.7 g, 0.04 mol),
and p-TsOH (0.076 g) were stirred at 120 °C for 50 min. GC
response factor analysis of a sample of the reaction mixture
indicated 1 was formed in 80% yield.
4
-Meth oxycin n a m ic Acid (5). A mixture of 3 and 4 (15:
1
,1,1,3-Tetr ach lor o-3-(4′-ch lor oph en yl)pr opan e (9).
Copper-diamine-catalyzed reaction of 4-chlorostyrene (8)
with CCl as described above proceeded at a much slower
85) (5.0 g, ∼0.02 mol), acetic acid (25 mL), p-TsOH (0.035 g),
and water (0.4 mL) was stirred at reflux for 1.5 h. The solvent
2 2
was evaporated, the product dissolved in CH Cl (150 mL), and
4
5
extracted with 10% KOH (2 × 100 mL). The aqueous layer
rate as compared to 2 and 6. The reaction went to
completion in ∼7 h. Compound 9 failed to react with
ethanol in the presence of a catalytic amount of p-TsOH,
and after several hours at reflux, only starting material
was recovered.
was combined and acidified with dilute HCl. The precipitated
solid was collected by filtration, washed with water, and dried
to afford 5 as a white solid (0.52 g, 15% yield). Mp 169-173 °C,
mixed melting point with an authentic sample (Aldrich) 173-
1
76 °C.
,1,1,3-Tetr a ch lor o-3-(4′-a cetoxyp h en yl)p r op a n e (7). A
solution of 6 (8.1 g, 0.05 mol), CCl (25 g, 0.162 mol), CuCl (0.2
g, 0.002 mol), and TMEDA (0.46 g, 0.004 mol) was stirred at
reflux for 1.5 h. The reaction mixture was extracted with CCl
1
4
Exp er im en ta l Section
4
Melting points were determined on a Mel-Temp melting point
1
13
and methylene chloride, filtered, and concentrated in vacuo to
afford a green solid. GC analysis of this solid indicated that 7
had been formed with 99% selectivity, and the product was
apparatus. H and C NMR spectra were recorded on a 200
MHz and a 400 MHz spectrometer. The chemical shifts are
reported on δ scale. The coupling constants are reported in
hertz. IR spectra were recorded on a FT-IR spectrometer. GC
analyses were done on gas chromatograph equipped with a 30
meter DB-1, 1.0 µm column with 0.32 i.d. GC/MS spectra were
obtained on a benchtop instrument equipped with a mass
selective detector. Mass spectra were obtained on a EI-CI
spectrometer system. 4-Methoxystyrene, 4-acetoxystyrene, and
4
isolated in 93% yield. Recrystallization with CCl afforded white
1
crystals: mp 71 °C; H NMR δ: 7.26 (q, 4 H, aromatic), 5.30 (t,
1
1
H), 3.55 (m, 2H), 2.30 (s, 3 H); 13C NMR δ: 169.2, 150.9, 137.9,
28.5, 122.1, 96.1, 62.7, 57.5, 21.0 ppm; MS: (chemical ionization
(9) (a) Schudel, P.; Schwarzenbach, R.; Gozenbach, H. U.S. Patent,
4
-chlorostyrene were either purchased from Aldrich Chemical
4713473, 1987. (b) The Merck Index, 12th ed. Merck & Co., Inc.:
Co. or synthesized from the corresponding acetophenonones via
Rahway, NJ , 1996; p 1163.