Jan-Feb 2001
Crown Type Macrocycles from a Polyether with 4-Pyrone Subunit
305
Werner Löwe* and Stefanie A. Brätter
Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany
Joachim Buddrus
Institut für Spektroskopie und Angewandte Spektroskopie, Bunsen-Kirchhoff-Str. 11, 44139 Dortmund, Germany
Received February 9, 2000
Our aim to enlarge the ring of the crown type compound 1, using the two component dilution principle,
leads to hitherto unknown macrocycles 6 and 7.
J. Heterocyclic Chem., 38, 305 (2001).
The synthesis is described according to Yamamoto et
al. as follows [1]: The crown type compound 1 which is
synthesized from 2,6-bis(bromomoethyl)-4-pyrone and
obtained on a Finnigan MAT Bremen CH-7A spectrometer and
Finnigan MAT Bremen CH-5DF. FAB spectra were determined
on a CH-5-DF-MAT-Varian (80 eV). Elemental analyses were
performed by the Institut für Pharmazie Analytical Service
Laboratory.
1
,5-bis(hydroxyphenoxy)-3-oxapentane [2], was treated
with phosphorous pentasulfide in benzene followed by
an excess of methyl iodide to afford the corresponding
pyrylium compound 3. This salt was hydrolyzed with
potassium carbonate in aqueous methanol solution to
give the ring-opened diketone 4. This diketone was with-
out isolation desulfurized with Raney nickel in ethanol
followed by aqeous titanium trichloride to provide the
macrocyclus 5 and the diasteromeric diol 6. Compound
2,9,12,15,22-Pentaoxa[2.7]-o-cyclo[2]-(2,6)-pyranophan-
28-thione (2).
To crown type compound 1 [1] (2 g, 4.873 mmoles) in dry
benzene (100 ml) phosphorous pentasulfide (1.12 g,
5.06 mmoles) was added, and the mixture was heated to reflux
for 1 hour. After cooling the mixture was filtered and the solution
was removed by evaporation at room temperature. The residue
was purified by column chromatography (silica gel, ethyl
acetate). Pure fractions were combined and concentrated. Red
crystals were obtained from ethyl acetate/n-hexane, yield 1.5 g
5
could not be isolated because a transformation to the
cyclohexanone compound 7 takes place on account of an
excess of potassium carbonate.
-1 1
(
72%), mp 162 °C; ir (potassium bromide): ν 1648, 1256 cm ; H
Compound 6 is obtained as a 1:1 mixture of diastere-
nmr (deuteriochloroform): δ 3.93-3.95 (m, 4H), 4.19-4.21 (m, 4H),
1
3
1
omers as can be seen from the C nmr spectrum, in which
4.92 (s, 4H), 6.92-7.05 (m, 8H), 7.30 (s, 2H); H nmr (deuterio-
1
all signals are split into two lines. Interestingly, the H nmr
acetonitrile): δ 3.86-3.87 (m, 4H), 4.13-4.14 (m, 4H), 4.87 (s, 4H),
+
6
.95-7.05 (m, 8H), 7.30 (s, 2H); EI-ms: m/z 426 (M ).
spectrum displays two signals for the OH protons at 2.87
and 3.12 ppm; one signal belonging to one diastereomer
and the other to the second diastereomer.
Anal. Calcd. for C23H22O S (426.49): C, 64.77; H, 5.20.
6
Found: C, 64.63; H, 5.34.
The constitution follows from DEPT-135 °C 13C nmr
spectrum. To determine the con-figuration at the
cyclohexanone ring of compound 7, several NOE
experiments were performed. Irradiation of HC causes
2,9,12,15,22-Pentaoxa[2.7]-o-cyclo-[2]-28-methylthio-(2,6)-
pyrylophanium Iodide (3).
An excess of methyl iodide (2 ml, 32.06 mmoles) was added
to a mixture of 2 (1.5 g, 3.527 mmoles) in dry ethyl acetate
(70 ml) and heated to reflux for 90 minutes. The mixture was
filtered and the solvent was evaporated at room temperature to
give 1.66 g (83%) of a red solid, which was diluted with
acetonitrile (5 ml) and filtered again. The red crystals were
dried at 70 °C for 24 hours. Yield 1.56 g (78%), mp 122 °C; ir
signal enhancement of both HD and H , but not H .
B
A
Therefore, HC must be equatorial. Irradiation of HD
results in signal enhancement of H and H , but not of
C
B
H . The OH group is also equatorial. These results are
A
only in accord with the depicted conformation, thus the
compound 7 has the cis-configuration (O-Ar and OHD
on the same side).
-
1
(
potassium bromide): ν 1633, 1254 cm ; uv (dichloro-
1
methane): 328 nm; H nmr (deuterioacetonitrile): δ 2.87
(s, 3H), 3.69-3.71 (m, 4H), 4.10-4.12 (m, 4H), 5.31 (s, 4H),
6
.94-7.17 (m, 8H), 8.00 (s, 2H).
Anal. Calcd. for C H IO S⋅2H O (604.46): C, 47.69; H,
2
4
25
6
2
EXPERIMENTAL
4
4
.84. Found: C, 47.94; H, 4.64.
,8-Dihydroxy-2,10,17,20,23-pentaoxa[9.7]-o-cyclophane (6)
Melting points were determined on a Linström apparatus and
are uncorrected. The uv spectrum was obtained on a HP 8451A
Diode Array Spectrophotometer. The ir spectra were recorded on
1
7,22
(
mixture of diastereomers), and 17-Hydroxy[0
][7.9]-
o-cyclophan-21-one (7).
1
13
a Perkin-Elmer 297 spectrometer. The H nmr and the C nmr
spectra were recorded on a Bruker AC 300 and a Bruker
AVANCECPX400spectrometerrespectively.Massspectrawere
A mixture of 3 (1.5 g, 2.64 mmoles), potassium carbonate
(411 mg, 2.98 mmoles) and aqueous methanol (20 ml, 50%) was
stirred first at 0 °C for 30 minutes and then 1 hour at room
Arquet
