Difunctional 28-Membered Cyclic Arylene Ethers

Full text of DOI:10.1021/jo970954g

J . Org. Chem. 1997, 62, 7503-7506
7503
Sch em e 1
Difu n ction a l 28-Mem ber ed Cyclic Ar ylen e
Eth er s
Harry W. Gibson,* Devdatt S. Nagvekar, and
Donghang Xie
Department of Chemistry, Virginia Polytechnic Institute and
State University, Blacksburg, Virginia 24061
Received May 30, 1997
In tr od u ction
We have prepared a number of mono- and difunctional
derivatives of bis(m-phenylene)crown ethers.1 We have
also synthesized nonfunctionalized arylene ether mac-
rocycles.2 For example, 40-membered cyclic arylene ether
disulfone 1a was synthesized starting from bisphenol-A
and bis(p-fluorophenyl) sulfone;2a,b sulfone ketone 1b and
sulfone phosphine oxide 1c were made analogously.2b,f,g
These macrocycles are building blocks for supramolecular
chemistry.3
Sch em e 2
Herein we describe the synthesis and characterization
of functionalized cyclic arylene ethers in order to provide
reactive macrocycles with high thermal stabilities.
Resu lts a n d Discu ssion
The syntheses of 28-membered cyclic arylene ether
diesters 6 and 7 were accomplished via a two-step method
(Scheme 1). Bis[p-(3-carbomethoxy-5-hydroxyphenoxy)-
phenyl] sulfone (4) was made in 49% yield by nucleophilic
aromatic substitution of bis(p-fluorophenyl) sulfone (3)
1
using excess methyl 3,5-dihydroxybenzoate (2). The H
NMR and FAB mass spectra were consistent with the
(1) (a) Delaviz, Y.; Gibson, H. W. Polymer Commun. 1991, 32, 103.
(b) Delaviz, Y.; Gibson, H. W. Org. Prep. Proc. Int. 1991, 23, 382. (c)
Delaviz, Y.; Shen, Y. X.; Gibson, H. W. Polymer 1992, 33, 212. (d)
Delaviz, Y.; Gibson, H. W. Macromolecules 1992, 25, 18. (e) Gibson,
H. W.; Delaviz, Y. Polymer 1994, 34, 1109. (f) Delaviz, Y.; Merola, J .
S.; Berg, M. A. G.; Gibson, H. W. J . Org. Chem. 1995, 60, 516. (g)
Nagvekar, D.; Gibson, H. W. Org. Prep. Proc. Int. 1997, 29, 237. (h)
Nagvekar, D. S.; Gibson, H. W. Org. Prep. Proc. Int. 1997, 29, 234. (i)
Nagvekar, D. S.; Yamaguchi, N.; Wang, F.; Bryant, W. S.; Gibson, H.
W. J . Org. Chem. 1997, 61, 4798. (j) Nagvekar, D. S.; Gibson, H. W.
Can. J . Chem., in press.
(2) (a) Ganguly, S.; Gibson, H. W. Macromolecules 1993, 26, 2408.
(b) Xie, D.; Gibson, H. W. Macromol. Chem. Phys. 1996, 197, 2133. (c)
Chen, M.; Gibson, H. W. Macromol. Chem. Phys. 1996, 197, 4069. (d)
Chen, M.; Gibson, H. W. Macromolecules 1996, 29, 5502. (e) Chen, M.;
Gibson, H. W. Macromolecules 1997, 30, 2516. (f) Xie, D.; Gibson, H.
W. Am Chem. Soc. Div. Polym. Chem., Polym. Prepr. 1994, 35, 401.
(g) Xie, D.; Gibson, H. W. Macromolecules 1997, 30, 4814-4827.
(3) Lehn, J .-M. Supramolecular Chemistry; VCH Publishers, Inc.:
New York, 1995. Cram, D. J .; Cram, J . M. Container Molecules and
Their Guests; Royal Society of Chemistry: Cambridge, U.K., 1994.
Vo¨gtle, F. Supramolecular Chemistry; J ohn Wiley & Sons: New York,
1991. Gibson, H. W.; Bheda, M. C.; Engen, P. T. Prog. Polym. Sci. 1994,
19, 843. Amabalino, D. B.; Stoddart, J . F. Chem. Rev. 1995, 95, 2725.
Gibson, H. W. In Large Ring Molecules; Semlyen, J . A., Ed.; J ohn Wiley
& Sons: New York, 1996; pp 191-262.
structure of 4. This compound exhibited a broad soften-
ing range; attempts to crystallize 4 were futile.
4 was also synthesized via the bis(benzyl ether) 10
(Scheme 2). Methyl 3-(benzyloxy)-5-hydroxybenzoate (8)
and bis(p-chlorophenyl) sulfone (9) yielded 10 (5%) along
with the byproducts methyl 3-(benzyloxy)-5-methoxyben-
zoate (11) and p-[3-carbomethoxy-5-(benzyloxy)phenoxy]-
phenyl p-chlorophenyl sulfone (12) in 25% and 16%
yields, respectively. 11 probably arose by transesterifi-
S0022-3263(97)00954-7 CCC: $14.00 © 1997 American Chemical Society

7504 J . Org. Chem., Vol. 62, No. 21, 1997
Notes
F igu r e 2. 1H NMR spectrum (400 MHz) of 7 in CDCl3.
F igu r e 1. 1H NMR spectrum (400 MHz) of 6 in CDCl3.
cation of 8, the carboxylate ion serving as a leaving group.
12 represents conversion of only one of the two halide
groups of 9 to the desired phenoxy derivative, probably
because of the low reactivity of the dichloride 9 and
depletion of 8 by its side reaction to form 11. However,
10 was successfully converted (88%) to 4 by hydrogenoly-
sis.
The syntheses of macrocycles 6 and 7 were accom-
plished via 1 + 1 condensation of bisphenol 4 with bis(p-
fluorophenyl) sulfone (3) or 4,4′-difluorobenzophenone (5),
respectively, by aromatic nucleophilic substitution reac-
tions using a syringe pump to maintain psuedo-high-
dilution conditions4 (Scheme 1). These macrocycles were
obtained in low yields (19% and 10%, respectively) as
compared to 1a (67%) and 1b (68%) made under identical
conditions.2f,g The lower yields in case of 6 and 7 are
probably a direct result of the lower nucleophilicity of
the phenolates of linear precursor 4 because of the
electron-withdrawing carbomethoxy groups and the
smaller, more strained rings of 6 and 7 relative to 1a ,b.
Low reactivity was evident from the significant amounts
of starting materials which were identified during the
purification process. Transetherification is also a com-
mon side reaction during aromatic nucleophilic substitu-
tion reactions on activated dihalides.5
F igu r e 3. FAB mass spectrum of 6 in 3-nitrobenzyl alcohol
matrix.
The proton NMR spectrum of 6 (Figure 1), apart from
a sharp singlet due to the methyl protons, also contains
one triplet (Ha) and three doublets (Hb, H1, and H2),
consistent with the symmetrical nature of the macrocycle
6. The proton NMR spectrum of macrocycle 7 (Figure 2)
contains four doublets (H1-H4), the most downfield one
of which is appropriate for the aromatic proton next to
the sulfone linkage (H4), and three sets of triplets (Ha-
Hc), consistent with the unsymmetrical nature of the
macrocycle. The 13C NMR spectrum of 6 contained 10
signals and that of 7 indicated 17 nonequivalent carbons,
consistent with the structures of the macrocycles.
Figures 3 and 4 show the FAB mass spectra of
macrocycles 6 and 7, respectively. In each case the
F igu r e 4. FAB mass spectrum of 7 in 3-nitrobenzyl alcohol/
glycerol/trifluoroacetic acid matrix.
parent ion corresponds to the mass of the pseudomolecu-
lar ion (M + H)+, and a sodium complex ion is also
observed. In the case of 6 the Na complex ion is observed
at m/z 787.9; the loss of a methyl fragment from the
pseudomolecular ion (m/z 764.9) yields m/z 749 with a
relative intensity of 15%, and loss of methanol from the
pseudomolecular ion is also evident (m/z 732.9, 22). For
7 the sodium complex ion appears at m/z 763.4; loss of
(4) Knops, P.; Sendhoff, N.; Mekelburger, H.-B.; Vo¨gtle, F. Top. Curr.
Chem. 1991, 161, 1. Dietrich, B.; Viout, P.; Lehn, J .-M. Macrocyclic
Chemistry; VCH Publishers, Inc.: New York, 1993.
(5) Rose, J . B. Polymer 1974, 15, 456.

Notes
J . Org. Chem., Vol. 62, No. 21, 1997 7505
Cyclo[oxy-1,4-p h en ylen esu lfon yl-1,4-p h en ylen eoxy-5-
(m e t h oxyca r b on yl)-1,3-p h e n yle n e oxy-1,4-b e n zoyl-1,4-
p h en ylen eoxy-5-(m eth oxyca r bon yl)-1,3-p h en ylen e] (7). A
solution of 4 (1.10 g, 2.00 mmol) and 5 (436 mg, 2.00 mmol) in
DMAc (25 mL) was injected into a refluxing suspension of DMAc
(400 mL), toluene (240 mL), and K2CO3 (416 mg, 3.01 mmol) at
the rate of 1.0 mL/h. The suspension was mechanically stirred
and purged with N2. H2O generated was azeotroped by toluene
into a Dean-Stark trap. After injection, the reaction was
allowed to continue for 12 h. After cooling, the mixture was
filtered and solvent was evaporated; the resultant brown liquid
was then precipitated into aq HCl. The crude solid was filtered.
Pure 7 (143 mg, 9.8%, mp 342.0-344.6 °C) was obtained by flash
silica gel column chromatography using CHCl3/EtOAc (20:1) as
the solvent system. 1H NMR (CDCl3) δ (ppm): 3.96 (s, 6H), 6.83
(t, J ) 2.2 Hz, 2H), 6.88 (d, J ) 8.8 Hz, 4H), 7.07 (d, J ) 8.8 Hz,
4H), 7.62 (t, J ) 2.2 Hz, 2H), 7.78 (d, J ) 8.8 Hz, 4H), 7.83 (m,
6H) (Figure 2). 13C NMR (CDCl3) δ (ppm): 52.71, 115.42, 115.85,
118.00, 118.94, 119.02, 129.96, 132.37, 133.18, 134.37, 135.36,
154.23, 157.58, 159.15, 162.18, 165.26, 193.56 (17 peaks as
required). MS (FAB) m/z [rel int.]: 729.4 [(M + H)+, 100], 667.3
[(M + H)+ - 2 × OCH3, 3], 531.3 [(M + H)+ - C14H14O, 15]
(Figure 4). HRFAB calcd for C41H30SO11 [M + H]+ m/z 729.1430,
found 729.1425 (error 0.7 ppm).
two methoxy fragments from the pseudomolecular ion
(m/z 729.4) yields m/z 667.3 (3); the peak at m/z 531
corresponds to the loss of two methyl groups and a
C6H4OC6H4 unit. The high-resolution mass spectra of 6
and 7 confirm their structures.
Both macrocycles exhibited good thermal stability by
thermogravimetric analysis (TGA) under nitrogen: 453
and 405 °C for 6 and 7, respectively.
Con clu sion s
Two new 28-membered cyclic arylene ether diesters
were synthesized via a two-step approach. The linear
precursor 4 synthesized in the first step was cyclized with
either bis(p-fluorophenyl) sulfone (3) or 4,4′-difluoroben-
zophenone (5) to give macrocycle 6 or 7 in 19% and 10%
yields, respectively. These are building blocks for su-
pramolecular chemistry, including polyrotaxanes.3
Exp er im en ta l Section
Meth yl 3-(Ben zyloxy)-5-h yd r oxyben zoa te (8). A mixture
of 29.76 g (177 mmol) of 2, 9.07 g (375 mmol) of NaH, and 350
mL of DMF was stirred at 110 °C for 5 h and then cooled to rt.
A solution of 18.6 mL (156 mmol) of benzyl bromide in 5 mL of
DMF was added via syringe pump at a rate of 1 mL/h. After
addition the mixture was stirred at rt for 3 days, the DMF was
removed by rotary evaporation, and the residue was extracted
with Et2O. Evaporation of the extract gave 40.9 g of a gummy,
light brown product. Trituration with CH2Cl2 (DCM) produced
8.01 g of a light yellow solid, which was the starting 2; the filtrate
was evaporated to produce a gummy material. Silica gel
chromatography using DCM gave the dibenzyl ether [12.4 g,
28%, mp 65.1-67.6 °C (lit.6 mp 65.1-67.6 °C)] as the first
fraction, a mixture as the second fraction, and the third eluted
fraction as pure 8 (14.5 g, 43%), mp 96.2-97.6 °C (lit.6 mp 97-
98 °C). IR (KBr) cm-1: 3376 (br, OH), 1715 (CdO), 1602 (CdC).
1H NMR (acetone-d6) δ (ppm): 3.85 (s, 3H), 5.14 (s, 2H), 6.74 (t,
J ) 2.2 Hz, 1H), 7.1-7.4 (m, 5H), 7.51 (m, 2H, J ) 2.2 Hz), 8.84
(s, 1H).
Bis[p -[3-(b en zyloxy)-5-ca r b om et h oxyp h en oxy]p h en yl]
Su lfon e (10). A mixture of 10.40 g (75.2 mmol) of K2CO3, 16.25
g (63.0 mmol) of 8, 400 mL of DMAC, and 250 mL of toluene
was stirred for 25 h under reflux (oil bath at 140 °C) while H2O
was removed by azeotropic distillation into a Dean-Stark trap.
The toluene was then completely removed, and the oil bath
temperature was increased to 190 °C. 9 (8.96 g, 31.2 mmol) was
added all at once, and the reaction was continued for 24 h.
DMAc was then removed on a rotary evaporator, and the residue
was diluted with DCM and filtered through Celite. Evaporation
Ma ter ia ls a n d Mea su r em en ts. These have been previously
reported.1f,i Mass spectra (MS) were measured at the Nebraska
Center for Mass Spectrometry, Department of Chemistry,
University of Nebraska, Lincoln, NE, and the Washington
University Mass Spectrometry Resource in St. Louis, MO;
HRFAB, high-resolution FAB. TGA was performed at 10 °C/
min.
Bis[p-(3-ca r bom eth oxy-5-h yd r oxyp h en oxy)p h en yl] Su l-
fon e (4). K2CO3 (48.45 g, 350.6 mmol) was added to a solution
of 21d,j (53.09 g, 315.7 mmol) in a mixture of DMAc (250 mL)
and toluene (170 mL). The suspension was mechanically stirred
and purged with N2 while heating in an oil bath whose
temperature was 170 °C. H2O generated was azeotroped by
toluene into a Dean-Stark trap. After refluxing for 15 h most
of the toluene was removed and then 3 (4.10 g, 16.1 mmol) was
added. The reaction was allowed to continue for 20 h (oil bath
at 140 °C). After cooling, the mixture was filtered and solvent
was evaporated. The resultant brown liquid was precipitated
into aq HCl. The solution was decanted to recover oily material.
The oil was boiled in water to remove excess 2. After decantation
the oil was dissolved in CHCl3. Pure 4, 4.35 g (49%), “mp” 77.4-
88.3 °C, was obtained by flash silica gel column chromatography
with CHCl3/EtOAc (20:1) as the solvent system. 1H NMR
(CDCl3) δ (ppm): 3.82 (s, 6H), 6.79 (t, J ) 2.2 Hz, 2H), 7.04 (dd,
J ) 2.2, 1.2 Hz, 2H), 7.19 (d, J ) 9.0 Hz, 4H), 7.26 (dd, J ) 2.2,
1.2 Hz, 2H), 7.97 (d, J ) 9.0 Hz, 4H), 10.28 (s, 2H). 13C NMR
(CDCl3) δ (ppm): 52.35, 110.84, 111.79, 112.70, 118.45, 129.95,
132.35, 135.62, 155.87, 159.28, 160.81, 165.39 (12 peaks as
required). MS (FAB) m/z [assignment, rel int.]: 551.3 [(M +
H)+, 32], 519.3 [(M - OCH3)+, 84], 400.3 [(M + H)+ - C8H7O3,
7.3], 337.2 [100]. HRFAB calcd for C28H24SO10 [M + H]+ m/z
551.1012, found 551.1023 (error 2.0 ppm).
of the solvent left
a gummy residue. TLC indicated four
products. Flash column chromatography with 4:1 hexane/EtOAc
yielded as the fourth fraction pure 10, as a glassy solid (1.11 g,
4.9%). IR (KBr) cm-1: 1722 (CdO), 1582 (CdC), 1330 (asymm
SO2), 1151 (symm SO2). 1H NMR (CDCl3) δ (ppm): 3.89 (s, 6H),
5.09 (s, 4H), 6.84 (t, J ) 2.3 Hz, 2H), 7.03 (d, J ) 8.8 Hz, 4H),
7.30 (m, 2H), 7.4 (m, 10H), 7.51 (m, 2H), 7.88 (d, J ) 8.8 Hz,
Cyclobis[oxy-1,4-p h en ylen esu lfon yl-1,4-p h en ylen eoxy-
5-(m eth oxyca r bon yl)-1,3-p h en ylen e] (6). A solution of 4
(1.008 g, 1.825 mmol) and 3 (464 mg, 1.83 mmol) in DMAc (20
mL) was injected into a refluxing suspension of DMAc (400 mL),
toluene (240 mL), and K2CO3 (410 mg, 3.00 mmol) at the rate of
1.0 mL/h. The suspension was mechanically stirred and purged
with N2. H2O generated was azeotroped by toluene into a Dean-
Stark trap. After injection, the reaction was allowed to continue
for 12 h. After cooling, the mixture was filtered and solvent was
evaporated; the resultant brown liquid was precipitated into aq
HCl. The crude solid was filtered. Pure 6 (270 mg, 19.3%, mp
347-349 °C) was obtained by flash silica gel column chroma-
tography using CHCl3/EtOAc (20:1) as the solvent system and
recrystallization from CHCl3. 1H NMR (CDCl3) δ (ppm): 3.86
(s, 6H), 6.68 (t, J ) 2.2 Hz, 2H), 6.97 (d, J ) 9.0 Hz, 8H), 7.72
(d, J ) 2.2 Hz, 4H), 7.88 (d, J ) 9.0 Hz, 8H) (Figure 1). 13C
NMR (CDCl3) δ (ppm): 52.75, 115.18, 117.72, 119.01, 130.11,
134.52, 136.49, 155.87, 160.87, 165.11 (10 peaks as required).
MS (FAB) m/z [rel int.]: 787.9 [(M + Na)+, 9], 764.9 [(M + H)+,
100], 749.0 [(M + H)+ - CH3, 15], 732.9 [(M - OCH3)+, 22]
4H). Anal. Calcd for
Found: C, 66.92; H, 4.78.
C42H34SO10‚H2O: C, 67.37; H, 4.85.
Meth yl 3-(Ben zyloxy)-5-m eth oxyben zoa te (11). 11 was
obtained as an oil (4.2 g, 25%) (lit.7 mp 46.5-47.0 °C) as the
first fraction from the chromatography above. IR (neat) cm-1
:
3090-3003 (dCH), 2844 (CH), 1722 (CdO), 1596 (CdC), 1237
(asymm COC), 1058 (symm COC). 1H NMR (CDCl3) δ (ppm):
3.82 (s, 3H), 3.91 (s, 3H), 5.08 (s, 2H), 6.73 (t, J ) 2.3 Hz, 1H),
7.20 (t, J ) 2.3 Hz, 1H), 7.28 (t, J ) 2.3 Hz, 1H), 7.38 (m, 5H).
p-[3-(Ben zyloxy)-5-car bom eth oxyph en oxy]ph en yl p-Ch lo-
r op h en yl Su lfon e (12). 12 was obtained as an amorphous
yellow solid, “mp” 56-88 °C (1.57 g, 16%), as the second fraction
from the above chromatography. IR (neat) cm-1: 1722 (CdO),
(6) Schwender, C. F.; Pike, R. E.; Shavel, J ., J r. J . Med. Chem. 1975,
18, 211.
(7) Cannon, J . R.; Chow, P. W.; Fuller, M. W.; Hamilton, B. H.;
Metcalf, B. W.; Power, A. J . Aust. J . Chem. 1973, 26, 2257.
(Figure 3). HRFAB calcd for
765.1100, found 765.1117 (error 2.1 ppm).
C
40H29S2O12 [M + H]+ m/z

7506 J . Org. Chem., Vol. 62, No. 21, 1997
Notes
1582 (CdC), 1330 (asymm SO2), 1151 (symm SO2). 1H NMR
(CDCl3) δ (ppm): 3.90 (s, 3H), 5.09 (s, 2H), 6.84 (t, J ) 2.3 Hz,
1H), 7.03 (d, J ) 8.8 Hz, 2H), 7.20-7.45 (m, 6H), 7.48 (d, J )
8.8 Hz, 4H), 7.52 (m, 1H), 7.87 (d, J ) 8.6, 2H). MS (FAB, NaI)
m/z {rel. int.}: 853.3 {[M(35Cl) + 2Na + 2NaI]+, 0.8}, 705.4
{[M(37Cl) + 2Na + NaI]+, 6}, 703.4 {[M(35Cl) + 2Na + NaI]+,
14}, 682.9 {[M(37Cl) + Na + NaI]+, 5}, 680.9 {[M(35Cl) + Na +
NaI]+, 12}, 533.0 {[M(37Cl) + Na]+, 12}, 531.0 {[M(35Cl) + Na]+,
28}, 501.0 {[M(37Cl) + Na - 2O]+, 1}, 499.0 {[M(35Cl) + Na -
2O]+, 6}, 477.8 {[M(37Cl) - 2O]+, 3}, 475.8 {[M(35Cl) - 2O]+, 7},
348.9 {[M(35Cl) + Na - 2O - COOCH3 - CH2C6H5]+, 13}, 327.3
{[M(37Cl) - 2O - COOCH3 - CH2C6H5]+, 14}, 325.3 {[M(35Cl)
- 2O - COOCH3 - CH2C6H5]+, 28}, 199.0 {37}, 176.0 {100}.
HRFAB calcd for C27H22ClSO6 [M + H]+ m/z 509.0825, found
509.0808 (error 3.2 ppm).
After filtration of the catalyst the solution was concentrated and
subjected to silica gel column chromatography using ether to
afford 4 as a colorless solid, 380 mg (88%), “mp” 77.7-84.9 °C,
identical in all respects to the sample described above.
Ack n ow led gm en t. We acknowledge support from
NSF (DMR93-20196, CHE95-21738) for the work de-
scribed here. Partial support was also provided by the
NSF Science & Technology Center for High Performance
Polymeric Adhesives and Composites (Grant DMR91-
2004). MS were provided by the Nebraska Center for
Mass Spectrometry, Department of Chemistry, Univer-
sity of Nebraska, and by the Washington University
Mass Spectrometry Resource, an NIH Research Re-
source (Grant P41RR0954).
Bis[p-(3-ca r bom eth oxy-5-h yd r oxyp h en oxy)p h en yl] Su l-
fon e (4). A mixture of 570 mg (0.78 mmol) of 10, 30 mg of Pd/
C, and 15 mL of EtOAc was exposed to 60 psi of H2 for 30 min.
J O970954G