Regioselective synthesis of syn disubstituted dibenzo-30-crown-10 ethers

Article abstract of DOI:10.1016/j.tet.2009.01.039

A practical and regioselective synthetic method for the synthesis of syn substituted dibenzo-30-crown-10 ethers is reported. This novel methodology is reported with the syntheses of dibenzo crown ethers bearing nitro, formyl and carbomethoxy groups. The s

Full text of DOI:10.1016/j.tet.2009.01.039

Tetrahedron 65 (2009) 2285–2289
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Tetrahedron
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Regioselective synthesis of syn disubstituted dibenzo-30-crown-10 ethers
*
Piotr Pia˛tek , Aleksandra Litwin
Department of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
A practical and regioselective synthetic method for the synthesis of syn substituted dibenzo-30-crown-
10 ethers is reported. This novel methodology is reported with the syntheses of dibenzo crown ethers
bearing nitro, formyl and carbomethoxy groups. The synthesis of macrocyclization precursors was ac-
complished in three steps and featured an application of para-methoxybenzyl group (PMB) as protecting
group of phenol moiety that is orthogonal to NO2, CHO and COOMe groups. General non-high dilution
macrocyclization conditions have been developed that allow for the effective preparation of substituted
large crown ethers.
Received 4 November 2008
Received in revised form 17 December 2008
Accepted 9 January 2009
Available online 15 January 2009
Keywords:
Macrocycles
Crown compounds
Dibenzo-30-crown-10
Regioselectivity
Protecting groups
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
crown ethers are commercially available it is often applied for the
synthesis of disubstituted macrocycles. Unfortunately this method
The most recognizable member of crown ether family is un-
questionably 18-crown-6 and its benzo and dibenzo counterparts.
Their complexation properties are well documented and most
commonly studied.1 By comparison, comparatively less attention
has been paid to crown ethers possessing large macrorings.2 Those
crown ethers display interesting properties that can be employed in
variety of applications. Interestingly, very large crown ethers like
dibenzo-24-crown-8 and dibenzo-30-crown-10 exhibit, similarly
to dibenzo-18-crown-6, good selectivity for potassium cation.3 This
is a result of the ability of large, flexible crown ether to ‘wrap
around’ the metal cation, effectively enclosing it almost entirely
within an organic sheath. A similar binding mode is observed for
the natural potassium ionophores valinomycin and nonactin.4
Moreover, dibenzo-30-crown-10 encapsulates the flat bipyr-
idinium derived herbicide diquat.5 Furthermore, large crown ethers
effectively form interlocked structures like: pseudorotaxanes,6
rotaxanes,7 polyrotaxanes8 and canenanes.9 However, for the con-
struction of even more complex and functional supramolecular
architectures substituted crown ethers are required.10
leads to a mixtures of syn and anti regioisomers, which are, for large
dibenzo crown ethers, inseparable. Nevertheless, a mixture of iso-
mers is frequently used for the construction of supramolecular
structures.10a–d This leads inevitably to complications since posi-
tional isomers of crown ethers possess different complexing and
other physicochemical properties.
Another approach to disubstituted dibenzo crown ethers
employed mono O-substituted-4-substituted catechols as starting
materials for the regioselective synthesis of desired regioisomer of
the macrocycle.10f,12 Recently this method has been successfully
used in the construction of syn and anti isomers of di(carbome-
thoxybenzo)-24-crown-6 and di(carbomethoxybenzo)-30-crown-
10.13,14
Our interest in the preparation of substituted large crown ethers
was stimulated by the observation that, in the ‘wrap around’
complex of dibenzo-30-crown-10 with a potassium ion, aromatic
rings of the macrocycle are close to each other in near parallel
alignment.15 We envisioned that placing an anion binding group
(i.e., amide, urea or thiourea) on those aromatic rings would create
a molecular receptor that is able to bind simultaneously both cation
and anion (salt). Thus dibenzo-30-crown-10 substituted with
groups that are precursors of amine function are needed. In this
paper we report a synthetic strategy, which allows for the efficient
regioselective synthesis of syn disubstituted dibenzo-30-crown-10.
The preparation of three different syn disubstituted dibenzo-30-
crown-10 ethers bearing electron-withdrawing groups such as ni-
tro, formyl and carbomethoxy is described.
There are two main approaches for the synthesis of function-
alized dibenzo crown ethers. One is based on electrophilic aromatic
substitution of the catechol units of the parent macrocycle.10a–d,11
Since this strategy requires only one step and many of dibenzo
* Corresponding author. Tel.: þ48 22 822 0211x237; fax: þ48 22 822 5996.
E-mail address: ppiatek@chem.uw.edu.pl (P. Pia˛tek).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.039

2286
P. Pia˛tek, A. Litwin / Tetrahedron 65 (2009) 2285–2289
O
O
O
O
O
O
R
OH
OH
R
OH
R
O
O
R
TsO
OTs
PMBCl
(Pri)2NEt,
CHCl3, rt
K2CO3, DMF,
80 °C
OPMB
OPMB
PMBO
R = NO2
R = CHO
R = COOMe
1a R = NO2
1b R = CHO
50%
52%
2a R = NO2
2b R = CHO
88%
80%
1c R = COOMe 48%
2c R = COOMe 89%
TFA, CH2Cl2,
0 °C-rt
O
O
O
O
O
O
O
O
O
O
R
O
O
O
O
R
R
O
O
R
TsO
OTs
OH
HO
CsF, CH3CN,
65 °C
O
O
3a R = NO2
3b R = CHO
97%
98%
3c R = COOMe 86%
4a R = NO2
4b R = CHO
54%
46%
4c R = COOMe 45%
2. Results and discussion
for the synthesis of 1a due to reasonable yield of desired compound
and low yield of side products. The mono-PMB protected nitro-
catechol 1a was alkylated with tetraethyleneglycol bistosylate to
give the diprotected acyclic polyether 2a with a yield of 88%. The
acid mediated PMB group deprotection readily afforded diphenol
3a. With this product in hand we sought an efficient macro-
cyclization method. Two different approaches have been reported
for the synthesis of dibenzo-30-crown-10 and its substituted de-
rivatives.18 The Stoddart group employed NaH in THF under non-
high dilution conditions.5 Whereas very recently a high dilution
method for the preparation of di(carbomethoxybenzo)-30-crown-
10 has been reported.14 To avoid the high dilution method we
screened numerous conditions and found that using CsF in aceto-
nitrile allowed effective macrocyclization.19 Thus diphenol 3a was
reacted with tetraethyleneglycol bistosylate in the presence of CsF
to afford syn-di(nitrobenzo)-30-crown-10 ether in 54% yield. It is
important to note that chromatographic purification is not required
at any synthetic step leading to 4a.
The analogous protocol was applied for the preparation of syn-
di(formylbenzo)-30-crown-10 ether. Thus regioselective monop-
rotection of 4-formylcatechol afforded 1b (52%).20 The coupling of
1b with tetraethyleneglycol bistosylate lead to diprotected com-
pound 2b. Removal of PMB groups under an acidic condition gave
3b in nearly quantitative yield. In contrast, as reported in the lit-
erature, cleavage of benzyl groups from benzyl analogue of 3b leads
to the mixture of an aldehyde and alcohol.13 Thus the PMB pro-
tective group is superior compared to the benzyl group and allows
for the effective preparation of formyl groups containing precursors
of dibenzo crown ethers. Finally the cyclization reaction of 3b with
tetraethyleneglycol bistosylate afforded syn-di(formylbenzo)-30-
crown-10 ether 4b (46%).
It is known that catechols possessing an EWG group at the 4-
position could be O-alkylated predominantly at the 1-position.16
This regioselectivity is believed to be dictated by the stabilization of
the phenoxide ion in the position para to the EWG group. Using this
information Stoddart et al. recently reported that in the reaction of
triethyleneglycol bistosylate with 3,4-dihydroxybenzaldehyde only
one pure syn-isomer of the triethyleneglycol linked catechols is
formed.10f Macrocyclization of this product lead directly to syn-
di(formylbenzo)-24-crown-8. Attracted by this very short synthetic
pathway to substituted dibenzo crown ethers we reacted 4-nitro-
catechol with tetraethyleneglycol bistosylate in the presence of
K2CO3. Unfortunately, only 4-nitrobenzo-15-crown-5 was isolated
from the reaction mixture.
Therefore, we turned our attention to the longer approach,
which relied on the regioselective protection of one of hydroxyl
group of 4-substituted catechol. This methodology has been pre-
viously applied by various research groups for the preparation of
substituted crown ethers.5,13,14 Those research groups employ
benzyl group for the protection of 1-hydroxy group of catechol.
Although for our purpose the benzyl group was not a suitable
protecting group because for its deprotection, catalytic hydro-
genolysis is required. Under those conditions nitro as well as formyl
groups undergo reduction. Thus we sought an other protecting
group that could be cleaved by a non-reductive method. The para-
methoxybenzyl group (PMB) is a convenient alternative to the
benzyl group that could be deprotected under a variety of non-
reductive conditions.17 Thus, 4-nitrocatechol was reacted with
para-methoxybenzyl chloride in the presence of K2CO3 in actoni-
trile. Although, those conditions are most commonly employed in
benzyl monoprotection of catechol derivatives, in our case a com-
plicated mixture of isomeric monoprotected and diprotected
products was formed. From this mixture 38% of pure crystalline 1a
was isolated. In order to increase the yield of mono-PMB product
other reaction conditions were investigated. In particular, a variety
of bases including: Na2CO3, NaHCO3, Et3N, Pri2NEt, NaH, ButOH in
solvents like CH3CN, DMF, CH2Cl2, THF have been tested. Un-
fortunately we found that none of the tested conditions allow for
the synthesis of 1a with yields much exceeded 50%. The procedure
employing Pri2NEt as a base and CH2Cl2 as a solvent was selected
To compare the efficiency of our macrocyclization methodology
with the high dilution technique we attempted to prepare syn-
di(carbomethoxybenzo)-30-crown-10 the compound synthesized
very recently by the Huang group.14 Thus reaction of the 4-carbo-
methoxy catechol with PMBCl in the presence of Pri2NEt gave 1c.
Subsequent alkylation of free hydroxyl groups and removal of
protective groups afforded diphenol 3c. The macrocyclization of 3c
with tetraethyleneglycol bistosylate in the presence CsF in aceto-
nitrile furnished di(carbomethoxybenzo)-30-crown-10 in a 45%
yield. Although our macrocyclization method gave 4c in a yield,

P. Pia˛tek, A. Litwin / Tetrahedron 65 (2009) 2285–2289
2287
which is 10% lower than reported for high dilution conditions, it
does not require elongated syringe pump reagent addition.
7.45–7.34 (m, 4H), 7.05 (d, J¼8.0, 1H), 6.97–6.92 (m, 2H), 5.78 (s, 1H,
–OH), 5.13 (s, 2H, –CH2–), 3.84 (s, 3H, –OCH3).
4.1.3. 2-(4-Methoxybenzyloxy)-4-methoxycarbonylcatechol (1c)
The solvent was removed in vacuo to give the crude material,
which was purified by column chromatography (hexanes/CH2Cl2
1:4 then CH2Cl2) to give 1c as a white solid (48%). Mp¼119–121 ꢀC;
Rf (40% AcOEt/hexanes)¼0.44; 1H NMR (CDCl3) 7.61–7.56 (m, 2H),
7.36–7.32 (m, 2H), 6.96–6.90 (m, 3H), 5.79 (s, 1H, –OH), 5.07 (s, 2H,
3. Conclusions
We have presented a simple synthetic method for the synthesis
of syn disubstituted dibenzo-30-crown-10. The utility of this
method was confirmed by the preparation of dibenzo-30-crown-10
substituted by nitro, formyl and carbomethoxy groups. We have
demonstrated that application of PMB group for protection of
phenol moiety allows for the synthesis of dibenzo-30-crown-10
derivatives bearing groups susceptible to reductive conditions.
Moreover, we have successfully developed an effective non-high
dilution protocol for the macrocyclization reaction. This method-
ology should be of general utility for the preparation of other
substituted dibenzo crown ethers.
–CH2–), 3.87 (s, 1H, –OCH3), 3.82 (s, 1H, –OCH3 ); 13C NMR (CDCl3)
0
167.0 (C]O), 160.0, 149.9, 145.6, 129.9, 128.8, 127.8, 123.6, 122.9,
116.0, 114.4, 111.4, 71.1 (–CH2–), 55.5 (–CH3), 5.2 (–COOCH3).
4.2. General method for the alkylation of monoprotected 4-
substituted catechols
Monoprotected 4-substituted catechols 1a–c (3–13.2 mmol)
were dissolved in dry DMF (40–150 mL) in an oven-dried two neck
round bottom flask equipped with a dropping funnel and a reflux
condenser. To this solution, K2CO3 (9–39.6 mmol, 3 equiv) was
added followed by the addition of a solution of tetraethyleneglycol
bistosylate (1.5–6.6 mmol, 0.5 equiv) in dry DMF. The suspension
was then stirred at 80 ꢀC (oil bath temperature) overnight. DMF
was removed in vacuo and the residue was dissolved in CH2Cl2 and
washed with water. The aqueous layer was extracted twice witch
CH2Cl2. The combined organic layers were washed with brine, dried
over MgSO4, filtered through a cotton plug and concentrated. De-
tails of further product purification are described below.
4. Experimental section
General methods: 4-nitrocatechol, 3,4-dihydroxybenzaldehyde
and 3,4-dihydroxybenzoic acid were purchased from commercial
sources and used as received. All other commercially available re-
agents were also used as received. Solvents were purified and dried
prior to use following the guidelines of Perrin and Armarego.21
Methyl 3,4-dihydroxybenzoate and tetraethyleneglycol bistosylate
were prepared according to the literature.13,22 All reactions were
carried out under an argon atmosphere. Chromatographic
purification of products was accomplished using column chroma-
tography on Merck 60 silica gel 230–400 mesh. Thin layer chro-
matography (TLC) was done using Fluka silica gel matrix plates. The
1H and 13C NMR spectra were acquired with a Varian Unity Plus
200/50 MHz spectrometer. High resolution mass spectra (HRMS)
were obtained on a Micromass Quattro LC spectrometer. Melting
4.2.1. Tetraethyleneglycol bis[2-(4-methoxybenzyloxy)-5-
nitrobenzene] (2a)
The crude product was purified by crystallization from hot
CH2Cl2/Et2O 1:1 to afford 88% of the title compound as a light-
yellow solid. Mp¼108–110 ꢀC; Rf (50% AcOEt/hexanes)¼0.26; 1H
NMR (CDCl3) 7.85–7.77 (m, 4H), 7.34 (d, J¼8.8, 4H), 6.95–6.88 (m,
6H), 5.13 (s, 4H, –CH2–), 4.24–4.19 (m, 4H), 3.91–3.81 (m, 4H), 3.80
(s, 6H, –OCH3), 3.71–3.67 (m, 4H), 3.65–3.56 (m, 4H); 13C NMR
(CDCl3) 159.8, 154.4, 148.8, 141.6, 130.0, 129.3, 128.1, 127.9, 118.1,
114.2,112.5,109.0, 71.1 (2ꢁ–CH2–), 70.9, 69.6, 69.4, 55.4 (2ꢁ–OCH3).
HRMS (ESI): m/z calcd for C36H40N2O13Na 731.2428 found: 731.2424
[MþNa]þ.
points were measured with
uncorrected.
a Kofler instrument and are
4.1. General method for the regioselective monoprotection of
4-substituted catechols
To a mixture of 4-substituted catechol (6.4 mmol), N,N-diiso-
propylethylamine (1.3 mL, 9.6 mmol, 1.5 equiv) and tetrabutyl-
ammonium iodide (0.36 g, 0.96 mmol, 0.15 equiv) in 60 mL of
chloroform para-methoxybenzyl chloride (1.68 mL, 9.6 mmol
1.5 equiv) was added dropwise. The resulting mixture was stirred at
room temperature for 2 days. Products were purified as described
below.
4.2.2. Tetraethyleneglycol bis[2-(4-methoxybenzyloxy)-5-
formylbenzene] (2b)
The crude material was purified by column chromatography
(hexanes/AcOEt 1:1, then AcOEt) to give 2b as an oil, which solid-
ified upon standing (80%). Rf (80% AcOEt/hexanes)¼0.22; 1H NMR
(CDCl3) 9.81 (s, 2H, 2ꢁ–CHO), 7.42 (d, J¼1.2, 2H), 7.39–7.33 (m, 6H),
7.0 (d, J¼8.8, 2H), 6.91–6.87 (m, 4H), 5.12 (s, 4H, 2ꢁ–CH2–), 4.20 (t,
J¼4.8, 4H), 3.87 (t, J¼4.8, 4H), 3.70 (s, 6H, 2ꢁ–OCH3), 3.71–3.70 (m,
4H), 3.68–3.60 (m, 4H); 13C NMR (CDCl3) 191.1 (2ꢁ–CHO), 159.7,
154.4, 149.6, 130.4, 129.1, 128.4, 126.7, 114.2, 113.3, 112.1, 71.1, 70.9,
69.7, 69.0, 55.5 (2ꢁ–OCH3); HRMS (ESI): m/z calcd for C38H42O11Na:
697.2625; found: 697.2618 [MþNa]þ.
4.1.1. 2-(4-Methoxybenzyloxy)-4-nitrocatechol (1a)
The reaction mixture was diluted with 40 mL of hexanes and
filtered through short pad of silica gel (
f¼85 mm, 3 cm). The silica
gel was washed with CH2Cl2. The solvent was removed in vacuo to
give the crude material, which was crystallized from EtOH to give
the titled compound as yellow crystals (50%). Mp (EtOH)¼136–
138 ꢀC; Rf (40% AcOEt/hexanes)¼0.50; 1H NMR (CDCl3) 7.81–7.79
(m, 2H), 7.35 (d, J¼8.8, 2H), 7.0–6.92 (m, 3H), 5.90 (s, 1H, –OH), 5.14
(s, 1H, –CH2–), 3.83 (s, 1H, –CH3); 13C NMR (CDCl3) 160.4, 151.2,
146.02, 142.0, 130.1, 117.0, 114.5, 111.0, 110.5, 71.7 (–CH2–), 55.6
(–CH3); HRMS (ESI): m/z calcd for C14H13NO5Na: 298.0691; found:
298.0694 [MþNa]þ.
4.2.3. Tetraethyleneglycol bis[2-(4-methoxybenzyloxy)-5-
carbomethoxybenzene] (2c)
The crude material was purified by column chromatography
(hexanes/AcOEt 1:1) to give 2c as an oil, which solidified upon
standing (89%). Rf (60% hexanes/AcOEt)¼0.42; 1H NMR (CDCl3) 7.62
(dd, J¼8.2, 1.8, 4H), 7.57 (d, J¼1.8, 4H), 7.34 (d, J¼8.8, 4H), 6.93–6.86
(m, 6H), 5.08 (s, 4H, 2ꢁ–CH2–), 4.22–4.17 (m, 4H), 3.89–3.80 (m,
10H), 3.79 (s, 6H), 3.71–3.69 (m, 4H), 3.63–3.60 (m, 4H); 13C NMR
(CDCl3) 167.0 (2ꢁ–C]O), 159.6, 152.9, 148.6, 129.2, 128.7, 124.0,
123.1, 114.9, 114.1, 113.4, 71.1, 70.8, 69.7, 69.0, 55.5 (–OCH3), 52.0
4.1.2. 2-(4-Methoxybenzyloxy)-4-formylcatechol (1b)
The solvent was removed in vacuo to give the crude material,
which was purified by column chromatography (hexanes/CH2Cl2
1:4 then CH2Cl2) to give 1b as a white solid (52%). Mp¼124–127 ꢀC;
Rf (30% AcOEt/hexanes)¼0.57; 1H NMR (CDCl3) 9.840 (s, 1H, –CHO),

2288
P. Pia˛tek, A. Litwin / Tetrahedron 65 (2009) 2285–2289
(–COOCH3). HRMS (ESI): m/z calcd for C40H46O13Na: 757.2836;
found: 757.2829 [MþNa]þ.
148.6,142.1,118.2,111.7,108.7, 71.2, 70.9, 69.5, 68.0; HRMS (ESI): m/z
calcd for C28H38 N2O14Na: 649.2221; found: 649.2214 [MþNa]þ.
4.3. General method for the deprotection of monoprotected
tetraethyleneglycol derivatives
4.4.2. syn-Di(formylbenzo)-30-crown-10 ether (4b)
The crude material was purified by column chromatography
(acetone/hexanes/1:1, then 7:3) to give a white solid, which was
further purified by crystallization from EtOH to afford 4b in 46%
yield. Mp 123–124 ꢀC; Rf (80% acetone/hexanes)¼0.49; 1H NMR
(CDCl3) 9.82 (s, 2H, CHO), 7.43 (dd, J¼7.8, 1.8, 2H), 7.37 (d, J¼1.8, 2H),
6.94 (d, J¼8.0, 2H), 4.24–4.17 (m, 8H), 3.94–3.88 (m, 8H), 3.81–3.67
(m, 16H). 13C NMR (CDCl3) 191.0, 154.4, 149.3, 130.3, 126.9, 112.2,
111.4, 71.2, 71.1, 70.8, 69.6, 69.5, 69.2, 69.1. HRMS (ESI): m/z calcd for
C30H40O12Na: 615.2417; found: 615.2415 [MþNa]þ.
To the solution of 2a–c (1.2–5.2 mmol) in CH2Cl2 (3–10 mL)
cooled to 4 ꢀC trifluoroacetic acid (3–10 mL) was added. The cooling
bath was removed and the reaction mixture was stirred for 1 h. The
reaction mixture was then diluted with CH2Cl2 and water. The
aqueous layer was neutralized with 1 M NaOH, and the organic
phase was separated. The aqueous layer was extracted twice with
CH2Cl2. All combined organic extracts were dried (MgSO4), filtered
and concentrated. The obtained residue was redissolved in
hexanes/AcOEt 1:1 (40–100 mL) and filtered through short pad of
silica gel. The filtrate was discharged. Next the silica gel was washed
with acetone. The solvent was removed in vacuo to give diphenol of
type 3.
4.4.3. syn-Di(carbomethoxybenzo)-30-crown-10 ether (4c)
The crude material was purified by column chromatography
(CH2Cl2 then 2% MeOH/CH2Cl2) to give a white solid, which was
further purified by crystallization from EtOH to afford 4c in 45%
yield. Mp¼114–115 ꢀC; Rf (6% MeOH/CH2Cl2)¼0.32; 1H NMR
(CDCl3) 7.64 (dd, J¼8.2, 2.0, 2H), 7.52 (d, J¼2.0, 2H), 6.85 (d, J¼8.6,
2H), 4.21–4.16 (m, 8H), 3.92–3.78 (m,14H), 3.79–3.76 (m, 8H), 3.71–
3.69 (m, 8H); 13C NMR (CDCl3) 167.0 (2ꢁ–C]O), 153.0, 148.4, 124.1,
123.1, 114.6, 112.4, 71.2, 71.0, 70.9, 69.8, 69.6, 69.2, 69.0, 52.1
(–OCH3); HRMS (ESI): m/z calcd for C32H44 O14Na: 675.2629; found:
675.2237 [MþNa]þ.
4.3.1. Tetraethyleneglycol bis(2-hydroxy-5-nitrobenzene) (3a)
Yellow solid. Yield 97%. Mp¼81–82 ꢀC; Rf (80% acetone/
hexanes)¼0.90; 1H NMR (CDCl3) 8.59 (br s, –OH), 7.87 (dd, J¼8.2,
1.8, 2H), 7.79 (d, J¼1.8, 2H), 6.93 (d, J¼3.6, 2H), 4.26–4.25 (m, 4H),
3.91–3.89 (m, 4H), 3.77–3.72 (m, 8H); 13C NMR (CDCl3) 153.7, 145.9,
140.8, 119.8,115.4, 110.0, 70.7, 70.4, 69.6, 69.2, 60.7; HRMS (ESI): m/z
calcd for C20H24 N2O11Na: 491.1278; found: 491.1282 [MþNa]þ.
Acknowledgements
4.3.2. Tetraethyleneglycol bis(2-hydroxy-5-formylbenzene) (3b)
White solid. Yield 98%. Rf (AcOEt)¼0.25; 1H NMR (CDCl3) 9.79 (s,
2H, 2ꢁ–CHO), 8.44 (br s, 2H, 2ꢁ–OH), 7.44–7.40 (m, 4H), 7.0 (d,
J¼8.6, 2H), 4.27–4.23 (m, 4H), 3.92–3.88 (m, 4H), 3.76–3.69 (m, 8H);
13C NMR (CDCl3) 191.0 (2ꢁ–CHO), 153.6, 146.9, 130.2, 128.2, 115.9,
111.5, 70.4, 70.2, 69.3, 68.2; HRMS (ESI): m/z calcd for C22H26O9Na:
457.1475; found: 457.1475 [MþNa]þ.
Financial support from The State Committee for Scientific Re-
search (project T09A-012-030) is gratefully acknowledged.
References and notes
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4.3.3. Tetraethyleneglycol bis(2-hydroxy-5-carbomethoxy-
benzene) (3c)
White solid. Yield 86%. Mp 64–66 ꢀC (lit14 62–63 ꢀC); Rf (60%
AcOEt/hexanes)¼0.33; 1H NMR (CDCl3) 8.2 (br s, –OH), 7.58 (dd,
J¼8.2, 1.8, 2H, 2ꢁH5), 7.49 (d, J¼1.8, 2H), 6.85 (d, J¼8.2, 2H), 4.19–
4.14 (m, 4H), 3.84–3.79 (m, 4H), 3.82 (s, 6H, –OCH3), 3.66–3.3.65 (m,
8H); 13C NMR (CDCl3) 167.1 (2ꢁ–C]O), 151.9, 145.9, 125.2, 121.8,
115.6, 115.2, 70.5, 70.33, 69.4, 68.9, 52.1 (2ꢁ–OCH3).
4.4. General method for the crown ether formation
Diphenols 3a–c (0.85–3.5 mmol) were dissolved in dry aceto-
nitrile (50–150 mL) in an oven-dried two neck round bottom flask
equipped with a dropping funnel and a reflux condenser. To this
solution CsF (3.4–14 mmol, 4 equiv) was added followed by the
addition of a solution of tetraethyleneglycol bistosylate (0.85–
3.5 mmol, 1 equiv) in dry acetonitrile. The suspension was then
stirred at 65 ꢀC (oil bath temperature) for 3 days. The solution was
allowed to cool to room temperature and water was added to dis-
solve any solids. The solvent was removed in vacuo and the residue
was dissolved in CH2Cl2 and washed with water and saturated
sodium bicarbonate. The organic layer was dried over MgSO4, fil-
tered through a cotton plug and concentrated. Details of further
products purification are described below.
4.4.1. syn-Di(nitrobenzo)-30-crown-10 ether (4a)
The crude product was purified by crystallization from hot
AcOEt to afford 4a as a light-yellow solid. Yield 54%. Mp¼119–
123 ꢀC; Rf (80% acetone/hexanes)¼0.70; 1H NMR (CDCl3) 7.84–7.80
(m, 2H), 7.70–7.68 (m, 2H), 6.84 (dd, J¼8.9, 1.2, 2H), 4.02–4.14 (m,
8H,), 3.91–3.85 (m, 8H), 3.75–3.64 (m, 16H); 13C NMR (CDCl3) 154.5,
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