Synthesis of "calixarene-like" N,N-ditosyldiaza[3.3](1,4) naphthalenophanes

Article abstract of DOI:10.1039/b717797f

A series of new tetrahomodiazacalix[2]naphthalenes, containing 2,3-dialkoxy-substituted naphthalene units, have been synthesized and some of their properties are reported. All of the newly-synthesized macrocycles were highly symmetrical and conformational

Full text of DOI:10.1039/b717797f

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PAPER
www.rsc.org/njc | New Journal of Chemistry
Synthesis of ‘‘calixarene-like’’ N,N-ditosyldiaza[3.3](1,4)-
naphthalenophanesw
Huu-Anh Tran, Julie Collins and Paris E. Georghiou*
Received (in Gainesville, FL, USA) 16th November 2007, Accepted 11th January 2008
First published as an Advance Article on the web 12th February 2008
DOI: 10.1039/b717797f
A series of new tetrahomodiazacalix[2]naphthalenes, containing 2,3-dialkoxy-substituted
naphthalene units, have been synthesized and some of their properties are reported. All of the
newly-synthesized macrocycles were highly symmetrical and conformationally rigid and revealed
‘‘calixarene-like’’ 1,3- alternate type structures.
PCC-mediated oxidation of 1,4-bis(hydroxymethyl)-2,3-di-
Introduction
methoxynaphthalene (14)12 derived via a three-step sequence
from 2,3-dihydroxynaphthalene (11) afforded pure dialdehyde
15 in near-quantitative yields (Scheme 1). By comparison, the
direct diformylation of 2,3-dimethoxynaphthalene (12a) via a
dilithiation reaction14,15 afforded 15 in only at best, 10%
yields. Demethylation of intermediate 15 with BBr3 in DCM
at room temperature gave dialdehyde 16 in 73–100% yields
(Scheme 1). Our procedure proved to be more reproducible16
than that described by Reinhoudt.17 Application of the
Skattebøl formylation procedure,18 failed to give 16 directly
from 11.
There are several examples of homoazacalixarenes such as
1a–4 (Fig. 1) which have been reported by various research
groups.1–11 These compounds belong to a class of macrocyclic-
ring expanded calixarenes in which the methylene bridges are
partly, or completely, replaced by ÀCH2NRCH2À groups
(R = H, alkyl, benzyl, tosyl, etc.). Such homoazacalixarenes
are of considerable interest because they have been shown to
be moderate receptors for various guests such as alkali-metal
2+ 2,3
ions,2 UO2
,
Zn2+ 4 Co3+ 4 Nd3+ 5 Yb3+ 6
, , , , ammonium
anion7 and various fluorescent molecules.8,9 In general, these
homoaza calixarene analogues were prepared via Schiff base
intermediates,10 or via N-alkylation of the corresponding
precursors.1–9,11
The bis(methylamino) intermediates 19a–d were synthesized
from the corresponding bis(bromomethyl)naphthalenes 13a–d
via two-step Gabriel reactions (Scheme 2). Firstly, treatment of
each of the 2,3-dialkoxynaphthalenes 13a–d with potassium
phthalimide (17) in refluxing DMF afforded the corresponding
1,4-bis(N-phthalimidomethyl)-2,3-dialkoxynaphthalenes 18a–d,
each in high yields (70–93%). Subsequent treatment of each of
18a–d in the presence of hydrazine in refluxing methanol
produced the corresponding products 19a–d in 65–100%
yields. In the case of 18b, using ethanol as solvent resulted in
a lower yield (63%) of 19 than that obtained with methanol
which was quantitative.
To date, however, there have been no reports dealing with
analogous homoazacalixnaphthalenes and/or their deriva-
tives. In order to expand the known class of homohetero-
bridged isocalixnaphthalenes beyond the known homoxa-
(5 and 6)12 and homothia- (7 and 8)13 analogues, the synthesis
of the analogous N-substituted homoazaisocalixnaphthalenes
9a–d were undertaken (Fig. 2). Notably, CPK models sug-
gested that the N-tosyl side-arm substituents could efficiently
reduce the flexibility of compounds 9a–d and that these newly-
synthesized calixnaphthalenes 9a–d might serve as potentially
useful receptors for binding studies with neutral or ionic guest
species.
The Schiff-base approach was then first attempted using
Kuhnert’s procedure without using
a cationic template
(Scheme 3).15 However, none of the desired product was
obtained either at ambient temperature, or upon heating at
reflux for different reaction times, solutions of dialdehyde 15
and bis(aminomethyl)naphthalene 19a in either DCM, aceto-
nitrile19 or benzene. Employing MacLachlan’s acetonitrile–
chloroform conditions20 gave an unidentified resinous mixture
which was not soluble in most of the common organic solvents
and could not be characterized.
Results and discussion
In order to synthesize the target homoazaisocalixnaphthalenes
9a–d and 10a–d, we first attempted to employ the Schiff-base
approach involving the condensation between dialdehyde 15
or 16, with 1,4-bis(aminomethyl)-2,3-dimethoxynaphthalene
19a. These precursors were derived from 2,3-dihydroxy-
naphthalene (11) as shown below in Schemes 1 and 2, respec-
tively.
The condensation of 1,4-diformyl-2,3-dihydroxynaphtha-
lene (16) and 1,4-bis(aminomethyl)-2,3-dimethoxynaphthalene
(19a) (Scheme 3) was also attempted in several solvent condi-
tions (CH2Cl2,15 CH3CN,19 1 : 1 CH3CN–CHCl3,16b,20,21 or
1 : 1 MeOH–CH3CN17). In all cases, solutions of 16 were
either added dropwise, to solutions of 19a in the same solvent,
or vice versa, or using a two-syringe pump in order to add both
reactant solutions at the same rate. These reactions were
conducted at either room temperature (3–14 d) or at reflux
Department of Chemistry, Memorial University of Newfoundland, St.
John’s, NL, Canada A1B 3X7. E-mail: parisg@mun.ca
w Electronic supplementary information (ESI) available: General
experimental methods and spectra of all new compounds. See DOI:
10.1039/b717797f
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Fig. 1
(2–4 h). Under the conditions employed, the starting materials
TEA–pyridine23 however failed to produce any of the desired
products 24a–d. Nevertheless, when Hart’s protocol24 using a
two-phase system consisting of aqueous NaOH and DCM was
employed, compounds 24a–d were produced in 73–83% yields.
The coupling reactions between intermediates 13a–d and
24a–d, respectively, in DMF in the presence of Cs2CO3 however,
surprisingly produced 9a–d as the only products (Scheme 5).
None of the expected [2 + 2], coupling products e.g. 10a–d (or
higher), as were observed previously in the synthesis of homo-
oxa-5a–d or homothiocalixnaphthalenes 7a–d, were formed.
Examination of CPK models suggested that due to steric strain,
the desired [2 + 2] coupling products 10a–d were expected to be
more favorably formed over the [1 + 1] products, namely N,N-
ditosyldiaza[3.3](1,4)naphthaleneophanes (9a–d). Nevertheless,
(+)-APCI MS analysis all showed the correct molecular ion
peaks of 9a–d, respectively, at m/z 767.0, 823.3, 879.5, and 935.4
with 100% relative intensities.
were completely consumed. The products however were not
soluble in the common organic solvents and thus could not be
characterized. Similarly, attempts using Ba(CF3SO2)2 or
Ba(SCN)2 as the source of the Ba2+ template to prepare the
Schiff bases 20 or 21, following Reinhoudt’s protocol,17 in a
variety of solvents (CH2Cl2,15 CH3CN,19 1 : 1 CH3CN–
CHCl3,16b,20,21 1 : 1 MeOH–CH3CN17) at either room tem-
perature (1–3 d) or reflux temperatures (1–4 h), gave brown or
orange precipitates which were not soluble in most common
organic solvents and could not be characterized. No further
attempts were therefore carried out using this Schiff-base
approach.
An alternate approach using Anslyn’s procedure9 in which
1,4-bis(bromomethyl)-2,3-diethoxynaphthalene (13b)12 was
added to the mixture of 1,4-bis(aminomethyl)-2,3-dimethoxy-
naphthalene (19b) and TEA in DCM at room temperature
(Scheme 4) also gave only an intractable resinous mixture. The
expected cyclization, therefore, failed to form desired cyclic
products, e.g. 22b and 23b.
All of these newly-synthesized macrocyclic compounds 9a–d
had relatively simple ambient-temperature 1H NMR spectra
which indicated that they were highly symmetrical. The brid-
ging methylene groups of 9a–d were slightly more shielded in
‘‘Calixarene-like’’ N,N-ditosyldiaza[3.3](1,4)-
1
the following order: 9a 4 9b 4 9c 4 9d. Noticeably, the H
naphthalenophanes 9a–d
NMR spectra for compounds 9a–d all revealed AB-type
doublets of doublets for their bridging methylene groups, at
d 4.19 and 5.29 ppm; 4.13 and 5.24 ppm; 4.11 and 5.23 ppm;
and 4.09 and 5.23 ppm, respectively, thus indicating that
compounds 9a–d are conformationally rigid. This observation
is consistent with other [3.3](1,4)naphthaleneophanes.25
The formation of 9a was confirmed by its X-ray structure
(Fig. 3).26 The X-ray structure of 9c was also obtained, but
only for reference, because of its much lower refinement,27
Since both Anslyn’s procedure and the Schiff base approach
failed to give the desired precursors for 9a–d and/or 10a–d, a
different strategy (Scheme 5) involving coupling of
1,4-bis(bromomethyl)-2,3-dialkoxynaphthalenes (13a–d) and
1,4-bis(p-tolylsulfonylaminomethyl)-2,3-dialkoxynaphthalenes
(24a–d) was evaluated.22 The attempted ditosylation of 19a–d
by TsCl (Scheme 5) under various conditions using organic
bases such as TEA–THF,22 pyridine–THF or DCM,23 or neat
Fig. 2
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Scheme 1
Scheme 2
although for both 9a and 9c, molecular mechanics calcula-
tions28 suggested the same ‘‘1,3-alternate’’-type conformers29
as minimum energy conformers (see Fig. 3).
compounds and C60 and C70 in either toluene, or carbon disulfide
solutions, as monitored by both colour changes or by complexa-
1
tion-induced chemical shifts in their H NMR spectra, failed to
Pappalardo and co-workers30 previously found that the cou-
pling reaction between 1,4-bis(chloromethyl)-2,3,5,6-tetramethyl-
benzene (25) and monosodium p-toluenesulfonamide (26) also
formed only the [1 + 1] coupling product, 27. This product was
formed in 15% yield along with the substitution product 1,4-
bis(tosylaminomethyl)durene (28) in 36% yield (Scheme 6).
reveal any evidence for any such complexation.
Conclusions
In summary, both the N-alkylation and cyclic Schiff base
approaches failed to afford the desired precursors for synthesis
of homoazaisocalixnaphthalenes 9a–d and 10a–d but
instead give resinous intractable products or no reaction.
The coupling between 1,4-bis(p-tolylsulfonylaminomethyl)-
2,3-dialkoxynaphthalenes (13a–d) and 1,4-bis(bromomethyl)-
2,3-dialkoxynaphthalenes (24a–d), respectively, gave a series
Complexation with C60- or C70-fullerene guests
Molecular mechanics simulations suggested that both C60- or
C70-fullerene could potentially form inclusion complexes with
9a–d. Disappointingly, however, complexation tests with these
Scheme 3
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Scheme 4
of new corresponding N,N-ditosyldiaza[3.3](1,4)naphthale-
neophanes (9a–d) (or ‘‘tetrahomodiazaisocalix[2]naphtha-
lenes’’), respectively, in reasonable yields (29–48%) for such
TMEDA (3.0 mL, 20 mmol) in anhydrous Et2O (25 mL) at
0 1C was added dropwise 1.6 M n-BuLi in hexane (13 mL,
20 mmol), and the reaction mixture was then heated at reflux
for a further 10 h and cooled to room temperature. To the
reaction mixture DMF (1.6 mL, 20 mmol) was added drop-
wise, and the mixture was stirred for a further 30 min. Cool
water (20 mL) was added to the mixture, followed by aqueous
3 M HCl (4.0 mL). The mixture was extracted with Et2O (3 Â
40 mL). The organic layers were combined, washed with brine
(1 Â 40 mL), dried over MgSO4 and filtered. After the solvent
was removed under reduced pressure, the resulting residue was
purified by chromatography (2 : 98 EtOAc–hexane) to yield 15
(0.10 g, 10%) having identical characterization data to those
obtained from procedure 1.
1
macrocyclizations. The H NMR spectra of all of the macro-
cycles obtained showed clearly that they were highly symme-
trical and also conformationally rigid and thus could provide a
new series of pre-organized molecular scaffolds. The X-ray
crystal structures of 9a and 9c also revealed that the 1,3-
alternate conformations are most likely the dominant ones.
Complexation studies to evaluate the binding properties of
these new tetrahomodiazaisocalix[2]naphthalenes with neutral
fullerene guests failed to reveal any such binding. Nevertheless,
an extensive study employing various metal and transition-metal
ions4–6,31 will be undertaken and if any significant binding
properties are observed these will reported upon in due course.
1,4-Diformyl-2,3-dihydroxynaphthalene (16)
To a stirred solution of 15 (1.12 g, 4.50 mmol) in dry DCM (45
mL) was added dropwise a solution of BBr3 (1.7 mL, 18 mmol)
in dry DCM (17 mL) over 1 h. The reaction mixture was
stirred for a further 5 h, and cold water (100 mL) was then
added at 0 1C. The mixture was acidified with aqueous 6 M
HCl until pH reached 1–2, extracted with CHCl3 (3 Â 60 mL),
dried over anhydrous MgSO4 and filtered. After the solvent
was removed under reduced pressure, the residue was dried
over night on a vacuum pump to yield crude product (0.99 g,
100%), which was purified by chromatography (2 : 8 EtOA-
c–hexane) to yield 16 (0.72 g, 73%) as a yellow solid: mp
205 1C (decomp.) [lit.16b 4180 1C (decomp.)]; 1H NMR
d 7.58–7.60 (m, 2H), 8.39–8.41 (m, 2H), 10.9 (s, 2H), 13.0 (s,
2H, disappears upon D2O addition); 13C NMR d 115.6, 120.2,
126.4, 127.0, 155.2, 194.6; GCMS m/z (%) 216 (M+, 100),
188 (100).
Experimental
1,4-Diformyl-2,3-dimethoxynaphthalene (15)
Procedure 1: oxidation of 1,4-bis(hydroxylmethyl)-2,3-di-
methoxynaphthalene (14). To a stirred suspension of PCC
(1.86 g, 3.72 mmol) and 3 A molecular sieves (2.8 g) in CHCl3
(30 mL) at room temperature was added a solution of 1412
(0.51 g, 2.0 mmol) in CHCl3 (100 mL). The reaction mixture
was stirred for a further 3 h, filtered through a Florisils pad,
and then the residue was washed with CHCl3 (3 Â 30 mL). The
organic layer was dried over anhydrous MgSO4 and filtered.
After the solvent was removed under reduced pressure, the
crude product was purified by chromatography (1 : 9 EtOAc–
hexane) to yield 15 (0.46 g, 92%) as a yellow solid: mp 100–
101 1C (acetone–hexane) (lit.16b 101–102 1C); 1H NMR d 4.11
(s, 6H), 7.60–7.62 (m, 2H), 9.02–9.04 (m, 2H), 10.8 (s, 2H); 13
C
NMR d 63.2, 125.1, 128.2, 128.8, 129.0, 158.4, 192.2; GCMS
m/z (%) 244 (M+, 85), 229 (30), 169 (65), 102 (100).
1,4-Bis(N-phthalimidomethyl)-2,3-dimethoxynaphthalene (18a).
General procedure
Procedure 2: Direct diformylation of 2,3-dimethoxynaphtha-
To a stirred solution of crude 13a (3.74 g, 10.0 mmol) in DMF
(100 mL), was added potassium phthalimide (17) (4.07 g,
lene (12a). To a stirred solution of 12a (0.75 g, 4.00 mmol) and
Scheme 5
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APCI MS m/z (%) 535.1 (M+, 70), 388.1 (100), calc.: 534.37
for C32H26N2O6.
1,4-Bis(N-phthalimidomethyl)-2,3-di-n-propoxynaphthalene
(18c)
Using the general procedure for 18a, the reaction of the crude
13c (3.44 g, 8.00 mmol) and 17 (3.16 g, 17.1 mmol) gave crude
product (4.20 g, 93%) as a yellow powder, which was purified
by chromatography (DCM) to yield 18c (3.12 g, 69%) as a
light yellow powder: mp 193–195 1C; 1H NMR d 1.07 (t, J =
7.5 Hz, 6H), 1.87–1.94 (m, 4H), 4.24 (t, J = 6.5 Hz, 4H), 5.39
(s, 4H), 7.34–7.35 (m, 2H), 7.64–7.66 (m, 4H), 7.76–7.78 (m,
4H), 7.99–8.01 (m, 2H); 13C NMR d 10.8, 23.8, 34.1, 75.3,
123.4, 124.0, 124.3, 125.5, 129.5, 132.2, 134.0, 151.5, 168.3;
(+)-APCI MS m/z (%) 563.1 (M+, 40), 416.1 (100), calc.:
562.62 for C34H30N2O6.
1,4-Bis(N-phthalimidomethyl)-2,3-di-n-butoxynaphthalene
(18d)
Using the general procedure for 18a, the reaction of the crude
13d (5.50 g, 12.0 mmol) and 17 (4.89 g, 26.4 mmol) gave crude
product (6.77 g, 95%) as a yellow powder, which was purified
by chromatography (DCM) to yield 18d (4.96 g, 70%) as a
light yellow powder: mp 184–185 1C; 1H NMR d 0.99 (t, J =
7.4 Hz, 6H), 1.49–1.57 (m, 4H), 1.83–1.89 (m, 4H), 4.28 (t, J =
6.7 Hz, 4H), 5.38 (s, 4H), 7.33–7.35 (m, 2H), 7.63–7.65 (m,
4H), 7.76–7.77 (m, 4H), 7.99–8.00 (m, 2H); 13C NMR d 14.3,
19.6, 32.7, 34.0, 73.7, 123.4, 124.0, 124.3, 125.5, 129.5, 132.2,
134.0, 151.6, 168.3; (+)-APCI MS m/z (%) 591.1 (M+, 70),
444.2 (100), calc.: 590.68 for C36H34N2O6.
Fig. 3 ORTEP representation of 9a (top) showing its ‘‘1,3-alternate’’
conformation (solvent molecules were removed for clarity) identical
with its computer-generated lowest energy conformer (bottom).
22.0 mmol). The reaction mixture was heated at reflux
(153–160 1C) with stirring for 3.5 h, cooled to room tempera-
ture and then poured into cold water (500 mL). The resulting
precipitate was filtered and dried at 60 1C to afford crude
product (4.20 g, 83%) as a light yellow powder, which was
purified by chromatography (5 : 95 EtOAc–DCM) to yield 18a
(3.34 g, 66%) as also a light yellow powder: mp 270–272 1C;
1H NMR d 4.09 (s, 6H), 5.37 (s, 4H), 7.37–7.39 (m, 2H),
7.64–7.66 (m, 4H), 7.77–7.78 (m, 4H), 8.06–8.08 (m, 2H); 13C
NMR d 33.8, 61.0, 123.4, 124.0, 124.4, 125.7, 129.5, 132.2,
134.1, 152.0, 168.4; (+)-APCI MS m/z (%) 507.0 (M+, 40),
360.1 (100), calc.: 506.51 for C30H22N2O6.
1,4-Bis(aminomethyl)-2,3-dimethoxynaphthalene (19a). General
procedure
The suspension of 18a (3.04 g, 6.00 mmol) and hydrate
hydrazine (2.4 mL, 48 mmol) in MeOH (85 mL) was heated
at reflux with stirring for 4 h. After the solvent was removed
under reduced pressure, the residue was dissolved in distilled
water (50 mL) and extracted with CHCl3 (3 Â 50 mL). The
organic layers were combined, washed with distilled water (2 Â
50 mL), brine (1 Â 50 mL), dried over anhydrous MgSO4 and
filtered. After the solvent was removed under reduced pres-
sure, the residue was dried overnight on a vacuum pump, to
yield 19a (1.29 g, 88%) as a yellow oily liquid: 1H NMR d 1.59
(s, br, 4H, disappears upon D2O addition), 3.96 (s, 6H), 4.29
(s, 4H), 7.47–7.50 (m, 2H), 8.05–8.07 (m, 2H); 13C NMR d
36.7, 61.5, 124.1, 125.6, 130.0, 130.9, 150.0; GCMS m/z (%)
246 (M+, 45), 202 (95), 171 (70), 128 (60), 115 (100).
1,4-Bis(N-phthalimidomethyl)-2,3-diethoxynaphthalene (18b)
Using the general procedure for 18a, the reaction of the crude
13b (2.81 g, 6.99 mmol) and 17 (2.76 g, 14.9 mmol) gave the
crude product (3.11 g, 83%) as a light yellow powder, which
was purified by chromatography (3 : 7 EtOAc–hexane) to yield
18b (2.94 g, 79%) as a colourless powder: mp 238–240 1C; 1H
NMR d 1.46 (t, J = 7.1 Hz, 6H), 4.34 (q, J = 7.1 Hz, 4H),
5.38 (s, 4H), 7.36–7.38 (m, 2H), 7.64–7.65 (m, 4H), 7.76–7.78
(m, 4H), 8.03–8.05 (m, 2H); 13C NMR d 16.0, 34.1, 69.4, 123.3,
124.1, 124.3, 125.6, 129.5, 132.2, 134.0, 151.3, 168.3; (+)-
Scheme 6
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1,4-Bis(aminomethyl)-2,3-diethoxynaphthalene (19b)
2,3-Diethoxy-1,4-bis(p-tolylsulfonylaminomethyl)naphthalene
(24b). General procedure
Procedure 1. Using the general procedure for 19a, the
reaction of 18b (3.21 g, 6.00 mmol) and H2NNH2 (2.4 mL,
1
48 mmol) gave 19b (1.65 g, 100%) as a yellow oily liquid: H
To a stirred solution of 19b (1.75 g, 6.37 mmol) in DCM (2.0
mL) at room temperature was added an aqueous solution of
0.3 M NaOH (63.0 mL, 19.0 mmol). The reaction mixture was
stirred for another 10 min, and a solution of TsCl (3.65 g,
19.1 mmol) in DCM (75 mL) was added dropwise over 30 min
at room temperature. The reaction mixture was stirred for a
further 40 h. The organic layer was separated, and the aqueous
layer was extracted with CHCl3 (3 Â 50 mL). The organic
layers were combined, washed with water (2 Â 50 mL), brine
(1 Â 50 mL), dried over MgSO4 and filtered. After the solvent
was removed under reduced pressure, the resulting residue was
purified by chromatography (2 : 98 EtOAc–DCM) to yield 24b
(2.88 g, 77%) as a colourless powder: mp 210–211 1C; 1H
NMR d 1.23 (t, J = 7.0 Hz, 6H) 2.41 (s, 6H), 3.89–3.94 (q, J =
7.1 Hz, 4H), 4.51 (d, J = 5.3 Hz, 4H), 4.64 (t, J = 4.8 Hz, 2 H,
disappears upon D2O addition) 7.23 (d, J = 8.0 Hz, 4H),
7.40–7.42 (m, 2H), 7.72 (d, J = 7.7 Hz, 4H) 7.77–7.79 (m, 2H);
13C NMR d 15.9, 21.7, 38.6, 70.0, 124.0, 125.2, 126.4, 127.5,
129.6, 129.8, 136.7, 143.7, 149.9; (À)-APCI MS m/z (%) 581.1
([M À 1]À, 100), calc.: 582.7 for C30H34N2O6S2.
NMR d 1.46 (t, J = 7.1 Hz, 6H), 1.54 (s, br, 4H, disappears
upon D2O addition), 4.14 (q, J = 7.0 Hz, 4H), 4.30 (s, 4H),
7.47–7.49 (m, 2H), 8.05–8.07 (m, 2H); 13C NMR d 16.1, 37.0,
69.9, 124.2, 125.5, 130.0, 131.1, 149.2; GCMS m/z (%) 274
(M+, 45), 257 (20), 201 (100), 184 (40), 115 (100).
Procedure 2. Using 95% EtOH as solvent instead of MeOH
afforded 19b (63%) having identical characterization data to
those obtained by procedure 1.
1,4-Bis(aminomethyl)-2,3-di-n-propoxynaphthalene (19c)
Using the general procedure for 19a, the reaction of 18c
(2.25 g, 4.00 mmol) and H2NNH2 (1.6 mL, 32 mmol) gave
19c (1.21 g, 100%) as a yellow semisolid: mp 50–51 1C; 1H
NMR d 1.10 (t, J = 7.3, 6H), 1.59 (s, br, 4H, disappears upon
D2O addition), 1.84–1.91 (m, 4H), 4.02 (t, J = 6.8 Hz, 4H),
4.29 (s, 4H), 7.47–7.49 (m, 2H), 8.05–8.07 (m, 2H); 13C NMR
d 10.8, 23.9, 37.0, 76.1, 124.2, 125.5, 130.0, 131.1, 149.5;
GCMS m/z (%) 302 (M+, 60), 257 (20), 226 (60), 215 (100),
200 (63), 184 (45), 128 (50), 115 (60).
2,3-Di-n-propoxy-1,4-bis(p-tolylsulfonylaminomethyl)-
naphthalene (24c)
Using the general procedure for 24b, the crude product from
the reaction of 19c (0.50 g, 1.65 mmol) with TsCl (0.94 g, 2.0
mmol) was purified by chromatography (2 : 98 EtOAc–DCM)
to yield 24c (0.83 g, 83%) as a colourless powder: mp 199–
1,4-Bis(aminomethyl)-2,3-di-n-butoxynaphthalene (19d)
1
200 1C; H NMR d 0.91 (t, J = 7.2 Hz, 6H), 1.58–1.65 (m,
Using the general procedure for 19a, the reaction of 18d
4H), 2.41 (s, 6H), 3.78 (t, J = 6.7 Hz, 4H), 4.51 (d, J = 5.5 Hz,
4H), 4.62 (t, J = 5.8 Hz, 2H, disappears upon D2O addition),
7.22 (d, J = 8.1 Hz, 4H), 7.41–7.43 (m, 2H), 7.72 (d, J = 8.1
Hz, 4H), 7.79–7.81 (m, 2H); 13C NMR d 10.6, 21.7, 23.6, 38.5,
76.1, 124.0, 125.0, 126.4, 127.5, 129.6, 129.8, 136.7, 143.7,
150.1; (À)-APCI MS m/z (%) 609.1 ([M À 1À], 100), calc.:
610.8 for C32H38N2O6S2.
(2.95 g, 5.00 mmol) and H2NNH2 (2.0 mL, 40 mmol) gave
1
19d (1.08 g, 65%) as a light yellow liquid: H NMR d 1.01 (t,
J = 7.4 Hz, 6H), 1.51 (s, br, 4H, disappears upon D2O
addition), 1.53–1.60 (m, 4H), 1.80–1.86 (m, 4H), 4.06 (t, J =
6.7 Hz, 4H), 4.29 (s, 4H), 7.47–7.49 (m, 2H), 8.06–8.08 (m,
2H); 13C NMR d 14.2, 19.6, 32.8, 37.0, 74.4, 124.3, 125.5,
130.0, 131.1, 149.5; GCMS m/z (%) 330 (M+, 60), 285 (20),
240 (84), 229 (100), 184 (65), 128 (67), 115 (60).
2,3-Di-n-butoxy-1,4-bis(p-tolylsulfonylaminomethyl)-
naphthalene (24d)
2,3-Diethoxy-1,4-bis(p-tolylsulfonylaminomethyl)naphthalene
Using the general procedure for 24b, the crude product from
the reaction of 19d (0.83 g, 2.5 mmol) with TsCl (0.30 g, 7.5
mmol) was purified by chromatography (5 : 95 EtOAc–DCM)
to yield 24d (1.17 g, 73%) as a colourless powder: mp 190–
(24a). General procedure
To a stirred solution of 19a (0.25 g, 1.0 mmol) in DCM (1 mL)
at room temperature was added an aqueous solution of 0.2 M
NaOH (10 mL, 2.00 mmol). The reaction mixture was stirred
at room temperature a further 10 min, and a solution of TsCl
(0.39 g, 2.00 mmol) in DCM (9 mL) was added dropwise over
20 min. The reaction mixture was stirred for another 20 h, and
water (100 mL) was added to the mixture. The resulting
precipitate was filtered off, washed several times with DCM
and dried at 50 1C to afford 24a (0.44 g, 80%) as a light yellow
powder: mp 4257 1C (decomp.); 1H NMR d 2.42 (s, 6H), 3.65
(s, 6H), 4.32 (d, J = 5.3 Hz, 4H), 7.43 (d, J = 8.0 Hz, 4H),
7.46–7.48 (m, 2H), 7.76 (d, J = 8.7 Hz, 4H), 7.80 (t, J = 5.4
Hz, 2H, disappears upon D2O addition), 7.95–7.97 (m, 2H);
13C NMR d 21.0, 37.1, 60.8, 124.4, 124.5, 125.4, 126.7, 129.3,
129.6, 137.0, 142.7, 150.3; (À)-APCI MS m/z (%) 553.0
(M+, 100), calc.: 554.67 for C28H30N2O6S2.
1
192 1C; H NMR d 0.92 (t, J = 7.4 Hz, 6H), 1.30–1.37 (m,
4H), 1.54–1.60 (m, 5H, overlap with HOD signal), 2.41 (s,
6H), 3.82 (t, J = 6.8 Hz, 4H), 4.50 (d, J = 6.4 Hz, 4H), 4.63 (t,
J = 5.9 Hz, 2H, disappears upon D2O addition), 7.23 (d, J =
8.5 Hz, 4H), 7.41–7.43 (m, 2H), 7.72 (d, J = 8.6 Hz, 4H),
7.81–7.83 (m, 2H); 13C NMR d 14.2, 19.4, 21.7, 32.5, 38.6,
74.4, 124.0, 125.0, 126.4, 127.5, 129.6, 129.8, 136.7, 143.6,
150.1; (À)-APCI MS m/z (%) 637.2 ([M À 1]À, 100), calc.:
638.2 for C34H42N2O6S2.
Bis(N-tosylamide)azaisocalix[2]-2,3-dimethoxynaphthalene
(9a). General procedure
To a suspension of Cs2CO3 (0.36 g, 1.1 mmol) in dry DMF
(5 mL) was added dropwise a solution of 13a (187 mg,
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1180 | New J. Chem., 2008, 32, 1175–1182

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0.500 mmol) and 24a (277 mg, 0.500 mmol) in dry DMF (15
mL) at room temperature over 5 h using a syringe pump. The
reaction mixture was stirred for a further 40 h at room
temperature. After the solvent was removed under reduced
pressure, to the resulting residue was added distilled water (30
mL), and the mixture was extracted with CHCl3 (3 Â 30 mL).
The organic layer was combined, washed with distilled water
(2 Â 40 mL) and brine (1 Â 40 mL), dried over MgSO4 and
filtered. After the solvent was removed under reduced pres-
sure, the residue was purified by chromatography (DCM) to
yield 9a (0.14 g, 37%) as a light yellow powder: mp 4290 1C
(m, 2H); 13C NMR d 14.2, 19.6, 21.8, 32.7, 46.3, 74.8, 122.7,
125.0, 125.3, 128.0, 130.0, 130.3, 133.8, 143.8, 149.1; (+)-
APCI MS m/z (%) 935.4 (M+, 100), calc.: 935.3 for
C54H66N2O8S2.
Acknowledgements
This research was supported by the Natural Sciences and
Research Council of Canada (NSERC) and the Department
of Chemistry, Memorial University of Newfoundland.
1
(CHCl3–acetone) (decomp.); H NMR d 2.56 (s, 3H), 3.64 (s,
References
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7.01–7.03 (m, 2H), 7.49 (d, J = 7.5 Hz, 2H), 7.94 (d, J = 7.5
Hz, 2H), 8.05–8.08 (m, 2H); 13C NMR d 21.9, 45.9, 63.1,
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Using the general procedure for 9a, the coupling reaction
between 13b (0.20 g, 0.50 mmol) and 24b (0.29 g, 0.50 mmol)
gave the crude product, which was purified by chromatogra-
phy (DCM) to yield 9b (0.12 g, 29%) as a light yellow powder:
mp 4260 1C (CHCl3–acetone) (decomp.); 1H NMR d 1.18 (t,
J = 7.3 Hz, 6H), 2.55 (s, 3H), 3.69–3.75 (m, 2H), 3.87–3.92 (m,
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8.99–7.00 (m, 2H), 7.49 (d, J = 7.2 Hz, 2H), 7.93 (d, J = 8.0
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122.8, 125.0, 125.3, 128.1, 130.0, 130.3, 134.1, 144.0, 148.9;
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Bis(N-tosylamide)azaisocalix[2]-2,3-dipropoxynaphthalene (9c)
Using the general procedure for 9a, the coupling reaction
between 13c (0.21 mg, 0.50 mmol) and 24c (0.31 g, 0.50 mmol)
gave the crude product, which was purified by chromatogra-
phy (DCM) to give 9c (0.21 g, 48%) as a colourless powder:
mp 4280 1C (CHCl3–CH3CN) (decomp.); 1H NMR d 0.88 (t,
J = 7.5 Hz, 6H), 1.55–1.65 (m, 4H), 2.53 (s, 3H), 3.50–3.55 (m,
2H), 3.79–3.83 (m, 2H), 4.11 (d, J = 13.4 Hz, 2H), 5.23 (d,
J = 13.4 Hz, 2H), 6.99–7.01 (m, 2H), 7.47 (d, J = 8.8 Hz, 2H),
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21.8, 23.7, 46.3, 76.6, 122.7, 125.0, 125.3, 128.0, 129.9, 130.3,
133.8, 143.9, 149.0; (+)-APCI MS m/z (%) 879.5 (M+, 100),
calc.: 879.1 for C50H58N2O8S2.
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Using the general procedure for 9a, the coupling reaction
between 13d (0.23 g, 0.50 mmol) and 24d (0.32 g, 0.50 mmol)
gave the crude product, which was purified by chromatogra-
phy (1 : 9 EtOAc–hexane) to yield 9d (0.15 g, 31%) as a
colourless powder: mp 4290 1C (CHCl3–CH3CN) (decomp.);
1H NMR d 0.89 (t, J = 7.3 Hz, 6H), 1.26–1.34 (m, 2H),
1.36–1.43 (m, 2H) 1.47–1.52 (m, 2H), 1.55–1.62 (m, 2H), 2.54
(s, 3H), 3.52–3.57 (m, 2H), 3.81–3.85 (m, 2H), 4.09 (d, J =
13.3 Hz, 2H), 5.23 (d, J = 13.7 Hz, 2H), 6.99–7.01 (m, 2H),
7.48 (d, J = 8.7 Hz, 2H), 7.92 (d, J = 7.9 Hz, 2H), 7.98–8.00
ꢀc
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(I 4 2s(I)), R1 = 0.0795, wR2 = 0.2094 (observed), R1
=
0.0860, wR2 = 0.2094 (all reflections). CCDC reference number
673893. For crystallographic data in CIF or other electronic
format see DOI: 10.1039/b717797f.
27. The X-ray crystal structure of 9c was also obtained but with a
very low refinement (mainly due to the disorder inherent in the
propyl groups), with two extra crossing C–C bonds in its
structure.
28. Computer-assisted molecular modeling were conducted using
Spartan’04, V1.0.3, from Wavefunction, Inc., Irvine, CA, USA.
Calculations at the MP3 level of theory were conducted o the
optimized geometry of the host and/or complexes which were
obtained through molecular mechanics (MMFF94) conforma-
tional searches.
29. In this paper, ‘‘1,3-alternate’’ conformations of the syn (1,4)cyclo-
phanes refer to conformations in which two naphthyl sub-units
and two phenyl sub-units are oriented in opposite directions.
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26. X-Ray crystallographic data for 9a: C45.50H45.50Cl10.50N2O8S2,
ꢀ
1184.75, primitive triclinic cell, P1 (no. 2),
Mr
12.9568(11),
=
a
a
=
=
b
=
14.4422(14),
c
=
15.5453(12) A,
92.4503(16), b = 103.0694(12), g = 112.024(2)1, V = 2600.5(4) A3,
Z = 2; 31 107 independent reflections, 13 377 were observed
ꢀc
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2008
1182 | New J. Chem., 2008, 32, 1175–1182