Formation of Macrocyclic Ethers
J . Org. Chem., Vol. 63, No. 20, 1998 6819
(Z)-8-Hyd r oxy-3,6-d ioxa octyl 3-(Eth oxyca r bon yl)p r o-
p en oa te. A solution of (Z)-3-(ethoxycarbonyl)propenoyl chlo-
ride35 (0.11 mol) in THF (150 mL) was added to a stirred
mixture of triethylene glycol (33.0 g, 0.22 mol) and pyridine
(9.5 g, 0.12 mol) in THF (100 mL) under nitrogen. The solution
was stirred for 16 h, filtered, washed with ether, and concen-
trated. The residue was worked up and chromatographed
(ether/methanol, 95/5) as described for 5-hydroxy-3-oxapentyl
acrylate to afford (Z)-8-hydroxy-3,6-dioxaoctyl 3-(ethoxycar-
bonyl)propenoate (11.5 g, 38%) as an oil: 1H NMR δ 1.15 (3H,
t, J ) 7.1 Hz), 3.12 (1H, s), 3.43-3.61 (10H, m), 4.09 (2H, q, J
) 7.1 Hz), 4.19 (2H, t, J ) 4.8 Hz), 6.12 and 6.15 (2H, AB
system, J AB ) 11.9 Hz); 13C NMR δ 13.7, 60.9, 61.2, 63.8, 68.4,
69.9, 70.2, 72.3, 129.2, 129.9, 164.9.
) 7.0 Hz), 3.40 (2H, q, J ) 7.0 Hz), 3.46-3.55 (4H, m), 3.62
(2H, t, J ) 4.7 Hz), 4.19 (2H, t, J ) 4.7 Hz), 5.71 (1H, dd, J )
10.3, 1.5 Hz), 6.03 (1H, dd, J ) 17.4, 10.3 Hz), 6.30 (1H, dd, J
) 17.4, 1.5 Hz); 13C NMR δ 14.9, 63.4, 66.3, 68.8, 69.6, 70.4,
128.1, 130.7, 165.8. Anal. Calcd for C9H16O4: C, 57.43; H,
8.57. Found: C, 57.09; H, 8.68.
Similar methods were used for the preparation of the
following. 3,6,9-tr ioxa u n d ecyl a cr yla te (5c)40 (60%). Anal.
Calcd for C11H20O5: C, 56.88; H, 8.68. Found: C, 56.97; H,
8.78%. 3,6,9,12-Tetr a oxa tetr a d ecyl a cr yla te (5d ) (40%).
Anal. Calcd for C13H24O6: C, 56.51; H, 8.75. Found: C, 56.91;
H, 8.56. 3,6,9,12,15-P en ta oxa h ep ta d ecyl a cr yla te (5e)
(43%). Anal. Calcd for C15H28O7: C, 56.23; H, 8.81. Found:
C, 56.02; H, 8.71. 3,6,9,12,15,18-Hexa oxa eicosa n yl a cr y-
la te (5f) (50%). Anal. Calcd for C17H32O8: C, 56.03; H, 8.85.
Found: C, 56.25; H, 8.69. 3,6-Dioxa octyl 2-m eth ylp r op e-
n oa te (9a )41 (50%). Anal. Calcd for C10H18O4: C, 59.39; H,
8.97. Found: C, 59.50; H, 8.63. (E)-3,6-Dioxa octyl bu t-2-
en oa te (9b) (30%), prepared with potassium carbonate instead
of triethylamine. Anal. Calcd for C10H18O4: C, 59.39; H, 8.97.
Found: C, 59.32; H, 8.81. (Z)-3,6-Dioxa octyl 3-(eth oxyca r -
bon yl)p r op en oa te (9c) (50%). Anal. Calcd for C12H20O6: C,
55.37; H, 7.75. Found: C, 55.12; H, 7.70. (E)-3,6-Dioxa octyl
3-(eth oxyca r bon yl)p r op en oa te (9d ) (50%). Anal. Calcd for
(Z)-8-(Mesyloxy)-3,6-d ioxa oct yl 3-(et h oxyca r b on yl)-
p r op en oa te was prepared as described above for 5-(mesy-
loxy)-3-oxapentyl acrylate.
(Z)-8-Iod o-3,6-d ioxa oct yl 3-(et h oxyca r b on yl)p r op e-
n oa te (2c) was prepared from (Z)-8-(mesyloxy)-3,6-dioxaoctyl
3-(ethoxycarbonyl)propenoate as described for 5-iodo-3-oxap-
entyl acrylate (1a ) (60%). Anal. Calcd for C12H19IO6: C, 37.32;
H, 4.96; I, 32.86. Found: C, 37.21; H, 4.72; I, 33.03.
3,6,9-Tr ioxa u n d eca n -1-ol. A mixture of ethyl iodide (7.8
g, 0.05 mol), triethylene glycol (15 g, 0.1 mol), and ground
potassium hydroxide (3.1 g, 0.055 mol) in THF (100 mL) was
stirred for 4 h at room temperature, and the solvent was then
removed under reduced pressure. The residue was dissolved
in the minimum amount of water and extracted with CH2Cl2.
The combined organic phases were washed with 5% aqueous
hydrochloric acid and brine and dried. After concentration of
the solution, the residue was purified by chromatography
(ether/methanol, 96:4) to afford 3,6,9-trioxaundecan-1-ol38 (5.3
g, 60%). 1H NMR δ 1.06 (3H, t, J ) 7.1 Hz), 3.20 (1H, s), 3.37
(2H, q, J ) 7.1 Hz), 3.44-3.72 (12H, m).
C
12H20O6: C, 55.37; H, 7.75. Found: C, 55.50; H, 7.60. (E)-
3,6-Dioxa octyl 3-p h en ylp r op en oa te (9e) (40%). Anal. Cal-
cd for C15H20O4: C, 68.16; H, 7.63. Found: C, 67.94; H, 7.68.
Eth yl 2-Meth ylen e-4,7,10-tr ioxa d od eca n oa te. Triethy-
lamine (3.6 g, 36 mmol) was added to a solution of ethyl
2-(bromomethyl)propenoate36 (5.8 g, 30 mmol) and 3,6-diox-
aoctan-1-ol (4.8 g, 36 mmol) in CH2Cl2 at 0 °C. The mixture
was then warmed to room temperature, stirred for 30 min,
and finally heated to reflux for 24 h. This solution was then
washed with 5% aqueous hydrochloric acid and brine, dried,
and concentrated. Chromatography of the residue afforded
ethyl 2-methylene-4,7,10-trioxadodecanoate: 1H NMR δ 1.09
(3H, t, J ) 7.0 Hz), 1.18 (3H, t, J ) 7.2 Hz), 3.41 (2H, t, J )
7.0 Hz), 3.47-3.56 (8H, m), 4.10 (2H, q, J ) 7.2 Hz), 4.12 (2H,
t, J ) 1.5 Hz), 5.78 (1H, q, J ) 1.5 Hz), 6.17 (1H, q, J ) 1.5
Hz); 13C NMR δ 13.9, 14.9, 60.4, 66.4, 69.0, 69.6, 70.0, 70.3,
70.5, 125.2, 137.1, 165.5. Anal. Calcd for C12H22O5: C, 58.52;
H, 9.00. Found: C, 58.47; H, 9.04.
Deter m in a tion of Cycliza tion Kin etics. A solution of
the iodo compound (0.50 mmol) and a suitable GC reference
compound (0.35 mmol) in benzene was made up to 5.0 mL in
a standard flask, and a sample (1.0 mL) was placed in a
Schlenk tube. A 0.10 M solution of Bu3SnH in benzene was
similarly prepared, and a 1.0 mL sample in a small tube was
carefully placed in the Schlenk tube. The contents of the
Schlenk tube were degassed by three freeze-thaw cycles,
heated to the desired temperature for 5 min, and then mixed.
After a suitable time (10-60 min) the mixture was analyzed
by GC. Reactions at different concentrations were conducted
by appropriate accurate dilution of the reactant solutions.
Similar methods were used for the preparation of 3,6,9,12-
tetr a oxa tetr a d eca n -1-ol38 (65%) and 3,6,9,12,15-p en ta oxa -
h ep ta d eca n -1-ol39 (50%).
3,6,9,12,15,18-H exa oxa eicosa n -1-ol.39
A solution of
3,6,9,12-tetraoxa-12-(2-tetrahydropyranyl)dodecan-1-ol3 (8.3 g,
30 mmol), 1-chloro-3,6-dioxaoctane (4.6 g, 30 mmol) and
ground potassium hydroxide (1.7 g, 30 mmol) was heated to
90 °C. When the reaction was complete (GC), acetone (100
mL) was added, and the mixture was filtered and concentrated.
Chromatography of the residue gave 1,4,7,10,13,16,19-hep-
taoxa-1-(2-tetrahydropyranyl)heneicosane (4.5 g, 38%): 1H
NMR δ 1.08 (3H, t, J ) 7.0 Hz), 1.36-1.72 (6H, m), 3.39 (2H,
q, J ) 7.0 Hz), 3.43-3.55 (24H, m), 3.58-3.70 (2H, m), 4.45
(1H, t, J ) 3.4 Hz); 13C NMR δ 14.9, 18.9, 24.9, 30.0, 61.5,
66.0, 66.2, 69.9, 70.0, 98.5.
A solution of the foregoing THP ether (2.0 g, 5 mmol) and
p-toluenesulfonic acid (0.9 g, 5 mmol) in methanol (35 mL) was
heated at 70 °C for 12 h. The solvent was then removed under
reduced pressure, and the residual 3,6,9,12,15,18-hexaoxa-
icosan-1-ol was used without purification: 1H NMR δ 1.10 (3H,
t, J ) 7.0 Hz), 3.10 (1H, s), 3.45-3.68 (24H, m), 3.38 (2H, q, J
) 7.0 Hz); 13C NMR δ 14.9, 61.7, 66.1, 69.8, 69.9, 70.1, 70.2.
3,6-Dioxa octyl Acr yla te (5b). Treatment of 3,6-dioxaoc-
tan-1-ol with 1.0 molar equiv of acryloyl chloride (2.7 g, 30
mmol) and 1.1 equiv of triethylamine in dry THF for 16 h gave
the crude ester, which was dissolved in CH2Cl2, successively
washed with 5% aqueous hydrochloric acid, 5% aqueous
NaHCO3, and brine, and dried. The solvent was removed
under reduced pressure, and the residue was chromatographed
over silica gel (ether/pentane, 40:60) to afford 3,6-dioxaoctyl
acrylate (60%) as a pale yellow oil: 1H NMR δ 1.08 (3H, t, J
Ack n ow led gm en t. We gratefully acknowledge the
CNRS and Aquitaine for a BDI Scholarship to A.P.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectral data for compounds 5c-f and 9a -e (2 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
J O980259O
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