A new synthetic strategy to prepare throne and calix diastereoisomers of parallel tris-Trger's bases

Article abstract of DOI:10.1080/10610278.2011.632822

The calix diastereoisomers of the parallel tris-Trger's base (tris-TB) derivatives were suggested as potential cavitands in 2002, and the first members of this cavitand family were introduced in 2007. The synthetic strategy enabling the preparation of nap

Full text of DOI:10.1080/10610278.2011.632822

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A new synthetic strategy to prepare throne and calix
diastereoisomers of parallel tris-Tröger's bases
Martin Havlík a , Bohumil Dolenský a , Jiří Kessler a , Ivana Císařová b & Vladimír Král a
a Department of Analytical Chemistry, Institute of Chemical Technology, Prague, Czech
Republic
b Department of Inorganic Chemistry, Charles University, Prague, Czech Republic
Version of record first published: 28 Nov 2011
To cite this article: Martin Havlík, Bohumil Dolenský, Jiří Kessler, Ivana Císařová & Vladimír Král (2012): A new synthetic
strategy to prepare throne and calix diastereoisomers of parallel tris-Tröger's bases, Supramolecular Chemistry, 24:2, 127-134
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Supramolecular Chemistry
Vol. 24, No. 2, February 2012, 127–134
¨
A new synthetic strategy to prepare throne and calix diastereoisomers of parallel tris-Troger’s
bases
a
Martin Havlık *, Bohumil Dolensky , Jirı Kessler , Ivana Cısarova and Vladimır Kral
a
a
b
a
´
´
ˇ´
´ ˇ
´
´
´
aDepartment of Analytical Chemistry, Institute of Chemical Technology, Prague, Czech Republic; bDepartment of Inorganic Chemistry,
Charles University, Prague, Czech Republic
(Received 30 June 2011; final version received 13 October 2011)
¨
The calix diastereoisomers of the parallel tris-Troger’s base (tris-TB) derivatives were suggested as potential cavitands in
2002, and the first members of this cavitand family were introduced in 2007. The synthetic strategy enabling the preparation
of naphthalene and anthracene derivatives of parallel tris-TBs, i.e. preparation without any reduction step, is introduced.
Naphthalene calix-tris-TB derivative having a cavity volume of about 0.113 nm3 (65% of a-CD cavity) is prepared by
isomerisation in various acid conditions.
¨
Keywords: parallel tris-Troger’s base; diastereoisomerisation; cavitand
Introduction
More than 120 years ago, Troger prepared an unknown
derivatives (5). The key to the success is the preparation of
hexaamine intermediate 2 without using any reduction
step, since it is expected to be unstable in reduction
condition (5a).
¨
compound with basic character, today known as Troger’s
¨
base (TB) (1). TB derivatives are compounds containing
two aromatic systems annelated by 1,5-diazabicy-
clo[3.3.1]nonane (TB unit). The molecular features of TB
derivatives (C2 symmetry, concave V-shape and chirality)
predestine them to be building blocks for molecular
architecture (2). We have recently published a new type of
cavitand based on parallel tris-TB derivatives (3).
The preparation starts from mesitylene (Scheme 1).
Nitration of mesitylene followed by reduction gave
triamine 5 (6). The following reaction of triamine 5 with
di-tert-butyl dicarbonate (Boc2O) provided triamine 4.
The radical bromination gave the key tribromide 3 in 61%.
It is worth mentioning that two atropoisomers (symmetric
1
and unsymmetric) were observed in H NMR spectra of
both triamine 4 and tribromide 3, wherein the averaged
spectrum is observed above 508C.
Parallel tris-TBs include three TB units annelated to a
single arene (e.g. benzene). These compounds have two
diastereoisomers: non-cavity throne-tris-TB and calix-tris-
TB having a cavity compartment (Figure 1). Tris-TB
diastereoisomers can be interconverted to each other in
acid medium; thus, the cavity can be created or disposed
by a change in pH. This unique property differes calix-tris-
TBs from other known cavitands, such as cyclodextrins,
calixarenes, resorcinarenes, cucurbiturils and so on (4).
At present, we introduce a new synthetic method for
the preparation of tris-TBs derivative from naphthalene
and anthracene, their isomerisation under various acid
conditions and a molecular modelling study of calix-tris-
TB cavitands.
We alsotried an alternative way for preparing tribromide
3. Triamine 4 was treated with Boc2O (4-dimethylamino-
pyridine – DMAP as catalyst is required) to form fully
protected triamine 7. The following radical bromination of
triamine 7 gave tribromide 8. Tribromide 3 was obtained by
partial deprotection of tribromide 8 by the treatment with
trifluoroacetic acid (TFA). This latter synthetic method gave
lower overall yield (44%), but isolation and purification of
product are easier and more suitable for upscaling.
The treatment of tribromide 3 with arylamines
(Scheme 2) in the presence of K2CO3 produced
hexaamines 2 (41% yield of 2a and 20% yield of 2b).
Slightly better yields were obtained by the reaction
without K2CO3 (50% yield of 2a and 34% yield of 2b).
Surprisingly, analogous treatment of tribromide 8 with
arylamines gave no corresponding hexaamines; the steric
restraint of tert-butoxycarbonyl groups could be the
reason. Using stronger base and higher temperature gave a
mixture of unidentified compounds.
Results and discussion
Preparation
We established the preparation of parallel tris-TB
derivatives 1 based on the synthetic protocol, which
¨
were successful in the preparation of bis-Troger’s (bis-TB)
*Corresponding author. Email: havlikm@vscht.cz
ISSN 1061-0278 print/ISSN 1029-0478 online
q 2012 Taylor & Francis
http://dx.doi.org/10.1080/10610278.2011.632822
http://www.tandfonline.com

´
M. Havlık et al.
128
yield. On the other hand, tris-TB 1b is formed in only 26%
yield, and is followed by several unidentified compounds.
As was expected, formation of only throne-tris-TBs was
observed (3).
Suitable single crystal of throne-1a for single-crystal
X-ray diffraction was obtained by crystallisation from the
mixture of dichloromethane and methanol (Figure 2 left).
The crystal packing uncovered short contacts between two
molecules of throne-1a (Figure 2 right). The naphthalene
plane of one molecule is coplanar with the naphthalene
plane of the second molecule (p-p interaction, distance
of planes is 0.35 nm); in addition, a naphthalene hydrogen
atom of one molecule interacts with central benzene of the
second molecule (CH-p interaction, distance is 0.25 nm).
Diastereoisomerisation study
There are only a few studies dealing with diastereoisome-
risation of oligo-TB derivatives (7). A significant effect of
HCl was observed on the equilibrium ratio of diastereoi-
somers. The presence of HCl or NH4Cl increases yields of
cavity-like diastereoisomers in case of both bis-TBs and
linear tris-TBs. It was assumed that there is an interaction
between chloride anion and both aromatic sidewalls of
oligo-TBs. We therefore examined an effect of anions in
the acid medium on the throne-1a : calix-1a ratio.
Figure 1. Diastereoisomers of tris-TB 1a. (a) the structure and
optimised geometry of throne-1a and (b) the structure and
optimised geometry of calix-1a.
The final treatment of hexaamines 2 with paraformal-
dehyde in TFA produced corresponding tris-TBs 1
(Scheme 2). Tris-TB 1a was formed in excellent 88%
The diastereoisomerisation study (Scheme 3) was
performed at 608C with throne-1a, wherein neat TFA, or
1:1 mixture of TFA with 35% aq. HCl, 48% aq. HBr, 57%
Br
Boc
Boc
HN
H
N
H
N
HN
NH2
H2N
Boc2O
82%
Boc
Boc
NBS, AIBN, IR
61%
Br
NH
NH
Br
NH2
Boc
Boc
5
4
3
1. FHNO3, H2SO4
6, 95%
5, 72%
Boc2O, DMAP 71%
TFA 83%
2. SnCl2.2H2O, HCl
Br
Boc
Boc
N
Boc
N
Boc
N
N
Boc
Br
Boc
Boc
Boc
NBS, AIBN, IR
75%
N
N
Br
Boc
Boc
Mesitylene
Boc
Boc
7
8
Scheme 1. Preparation of tribromide 3.

Supramolecular Chemistry
129
R
Br
NH
Boc
HN
Boc
H
N
H
N
R =
HN
Boc
R-NH2
Boc
R
a, napht-2-yl
b, anthracen-2-yl
H
N
Br
R
NH
Br
NH
HN
Boc
Boc
3
2a (50%)
2b (34%)
(CH2O)n
TFA
(CH2O)n
TFA
N
N
N
N
N
N
N
N
N
N
N
N
Throne-1a
Throne-1b
88%
26%
Scheme 2. Synthesis of tris-TB 1a and 1b.
aq. HI, or 85% aq. H3PO4 was used. TFA was used to
maintain the solubility of throne-1a. The ratio of
diastereoisomers was followed by HPLC analysis
(Table 1). In all cases, the equilibrium was reached in
4 days. The treatment in TFA with 57% aq. HI led to
throne-1a decomposition. For preparative scale, diaster-
eoisomerisation of throne-1a in the mixture of TFA and
48% aq. HBr was chosen. In accordance with the previous
study, calix-1a was obtained in 4% yield.
Molecular modelling
Finally, we tried to estimate a cavity volume of calix-1a,
calix-1b and calix-9 (a benzene tris-TB derivative). The
molecular geometry of calix diastereoisomers was
optimised on DFT-level using B3LYP functional with 6–
31 g
basis set and dispersion correction (8). The cavity
**
of calix diastereoisomers was approximated by a truncated
cone, whose top radius was determined as a radius of the
Figure 2. The X-ray crystal structure of throne-1a (left), short contacts between two molecules of throne-1a (right).

´
M. Havlık et al.
130
N
N
N
N
N
N
H+
N
N
N
N
N
N
Throne-1a
Calix-1a
Scheme 3. Diastereoisomerisation of tris-TB 1a.
described circle defined by the upper carbon atoms of the
cavity sidewalls. The cone height was measured as a
distance between the plane of bottom benzene and the
plane of the upper carbon atoms of the cavity sidewalls
(Figure 3). All the measurements were lowered by 0.16 nm
(a van der Waals radius) and the volume was calculated
(Table 2). The cavity volume of calix-1a is 65% of a-CD
cavity, whereas calix-1b cavity is 124% of a-CD and 82%
of b-CD.
temperature (23–258C) in CDCl3 or DMSO-d6. Chemical
shifts (d) are presented in ppm and, coupling constants (J) in
Hz. The program MestReNova v. 6.02 was used for workup
of NMR spectra. Mass spectra were obtained by
electrospray ionisation (ESIþ) with a VG Analytical
ZAB-EQ spectrometer. HPLC (LC 5000 HPLC) was used
for the determination of ratio of diastereoisomers of tris-TB
1a. The program Gaussian 09 was used for the quantum
chemical calculations of molecules. The UCSF Chimera v.
1.5.3 was used to generate 3D model of molecules, and this
model was processed in Blender 2.5 to obtain cavity
˚
visualisation. Silica (32–63 D, 60 A) was used for column
chromatography.
Conclusion
In conclusion, we presented a new synthetic method for
the preparation of tris-TB derivatives resulting in
naphthalene throne-1a in 88% yield and anthracene
throne-1b in 26% yield. We found a slight influence of the
used acid on the diastereoisomerisation ratio of calix-1a
and throne-1a. We isolated a new cavitand, calix-1a,
having a cavity volume of about 0.113 nm3 (65% of a-CD
cavity). We demonstrated that tris-TB cavitands having a
deep-wall cavity can be prepared.
Preparations of triamines 4 and 7
Mesitylene (8.6 g, 71.6 mmol) was added to the nitration
mixture (42 ml of sulphuric acid and 21 ml of fuming nitric
acid), and the reaction mixture was stirred and kept under
08C in water cooling bath for 2 h. The reaction mixture was
then poured onto ice. Precipitated solid was filtered off,
washed with water and methanol and dried in vacuo to
obtain 17.4 g (95.3%) of 1,3,5-trinitromesitylene (6).
Compound 6 (3.0 g, 11.8 mmol) was treated with SnCl2·2-
H2O (31.8 g, 140.9 mmol) in concentrated HCl (300 ml) at
1058C for 5 h. The solution was carefully alkalinised at 08C
by concentrated aq. NH3 and extracted with dichloro-
methane. The organic parts were extracted by water, dried
over Na2SO4 and evaporated to dryness in vacuo to obtain
1.4 g (72.1%) of triamine 5. Triamine 5 (2.0 g, 12.1 mmol)
Experimental part
Measurements and materials
All chemicals were purchased from Sigma-Aldrich Co. and
TCI Europe N. V. and used without further purification.
NMR spectra were recorded on Varian Gemini 300 HC
(300.077 MHz for H and 75.460 MHz for 13C) at room
1
Table 1. Results of isomerisation study of tris-TB 1a.
608C
Ratio of diastereoisomers depending on the time of throne-1a : calix-1a
Acid medium
TFA
TFA : HCl
TFA : HBr
TFA : H3PO4
2 h
4 h
6 h
24 h
4 days
7 days
99.7 : 0.3
99.8 : 0.2
99.7 : 0.3
99.5 : 0.5
99.3 : 0.7
99.6 : 0.4
99.3 : 0.7
99.2 : 0.8
98.7 : 1.3
98.7 : 1.3
98.6 : 1.4
97.8 : 2.2
98.0 : 2.0
98.4 : 1.6
97.0 : 3.0
97.1 : 2.9
97.9 : 2.1
97.2 : 2.7
96.4 : 3.6
96.4 : 3.6
97.9 : 2.1
97.4 : 2.6
96.4 : 3.6
96.3 : 3.7

Supramolecular Chemistry
131
Figure 3. Optimised geometry of calix-tris-TB derivatives. The calculated cavity volume is indicated by a purple cone.
was treated with Boc2O (10.6 g, 48.6 mmol) in THF
(100 ml) at reflux for 2 days. The reaction mixture was
evaporated to dryness in vacuo, and the residue was
separated by column chromatography (dichloromethane/
methanol 95:5) to obtain 4.6 g (81.6%) of triamine 4.
Triamine 4 (3.0 g, 6.4 mmol) was treated with Boc2O (6.3 g,
28.9 mmol) and DMAP (37.0 mg, 0.3 mmol) in THF
(150 ml) at reflux for overnight. The reaction mixture was
evaporated to dryness in vacuo and triamine 7 was obtained
and purified by crystallisation from dichloromethane/petrol
ether 3.5 g (70.9%). 1,3,5-trinitromesitylene (6): 1H NMR
(CDCl3): d2.27 (9H, s). 13C APT NMR (CDCl3): d150.51
(C), 124.50 (C), 13.34 (CH3). 2,4,6-trimethylbenzene-
APT NMR (CDCl3): d151.17 (C), 135.80 (C), 133.85 (C),
82.37 (C), 28.04 (CH3), 13.20 (CH3). HR-MS (ESIþ) for
C39H63N3O12Na [M þ Na]þ calculated: 788.4304, found:
788.4285.
Preparations of tribromides 3 and 8
2,4,6-Tris(bromomethyl)-N1,N3,N5-tris(tert-
butoxycarbonyl)-2,4,6-trimethylbenzene-1,3,5-triamine
(3)
Procedure I. Triamine 4 (0.25 g, 0.54mmol) was treated
with N-bromosuccinimide (NBS, 0.35g, 1.97mmol) and
a,a0-azo-bis-isobutyronitrile (AIBN, 0.03g) in CCl4 (60 ml)
under irradiation bythe IRlampfor 5 h. Thereactionmixture
was evaporated to dryness in vacuo, and the residue was
separated by column chromatography (dichloromethane/
diethylether 3:1) to obtain 0.23g (61.0%) of tribromide 3.
1H NMR (DMSO-d6, 508C): d8.86 (3H, bs), 4.56 (6H, s),
1.46 (27H, s). 13C APT NMR (DMSO-d6): d153.69 (C),
137.37(C), 133.41(C), 79.18 (C), 28.21 (CH3), 25.75 (CH2).
HRMS (ESIþ): for C24H36Br3N3O6Na [M þ Na]þ calcu-
lated: 727.9985, 724.0026, 722.0046, found: 727.9978,
724.0022, 722.0046.
1
1,3,5-triamine (5): H NMR (DMSO-d6): d3.94 (6H, bs),
1.79 (9H, s). 13C APT NMR (DMSO-d6): d141.45 (C),
95.83 (C), 11.07 (CH3). N 1,N 3,N 5-tris(tert-butoxycarbo-
1
nyl)-2,4,6-trimethylbenzene-1,3,5-triamine (4): H NMR
(CDCl3, 508C): d5.83 (3H, bs), 2.17 (9H, s), 1.48 (27H, s).
13C APT NMR (CDCl3): d153.98 (C), 133.50 (C), 132.32
(C), 79.85 (C), 28.48 (CH3), 14.02 (CH3). HR-MS (ESIþ)
for C24H39N3O6Na [M þ Na]þ calculated: 488.2731,
found: 488.2724. N 1,N 1,N 3,N 3,N 5,N 5-hexakis(tert-
butoxycarbonyl)-2,4,6-trimethylbenzene-1,3,5-triamine
1
(7): H NMR (CDCl3): d2.02 (9H, s), 1.39 (54H, s). 13C
Table 2. Cavity parameters for calix-tris-TBs and cyclodextrins (4a).
c
b
a
N
N
calix-9
calix-1a
calix-1b
a-CD
b-CD
g-CD
a [nm]
b [nm]
c [nm]
h [nm]
0.63
–
–
0.26
0.053
0.65
0.74
–
0.45
0.113
0.65
0.74
0.89
0.64
0.215
0.47–0.53
0.60–0.65
0.75–0.83
0.79
0.174
0.79
0.262
0.79
0.427
V [nm3]

´
M. Havlık et al.
132
Procedure II. Tribromide 8 (0.50 g, 0.50 mmol) was
dissolved in dichloromethane (250 ml) and TFA (1 ml) was
added. The reaction mixture was monitored by TLC
analysis (toluene:ethyl acetate 5:1). The reaction mixture
was alkalinised by concentrated aq. NH3 (1 ml) in water
(250 ml). The organic part was extracted by water, dried
over Na2SO4 and dried in vacuo. Tribromide 3 was
obtained and purified by crystallisation from THF/petrol
ether 0.29 g (82.8%).
in 40ml of DMF at 508C for 2 h. The reaction mixture was
evaporated to dryness in vacuo, and the residue was
separated by column chromatography (toluene:ethyl acetate
1
5:1) to obtain 74mg (20.0%) of hexaamine 2b. H NMR
(CDCl3): d8.29 (3H, s), 8.19 (3H, s), 7.94 (3H, d, J ¼ 7.1),
7.91 (3H, d, J ¼ 7.1), 7.83 (3H, d, J ¼ 8.9), 7.47 – 7.30 (9H,
m), 7.16 (3H, bs), 7.05 (3H, d, J ¼ 8.9), 4.65 (3H, bs), 4.39
(6H, s), 1.34 (27H, s). 13C APT NMR (CDCl3): d155.44 (C),
145.70 (C), 137.23 (C), 133.43 (C), 132.54 (C), 130.35 (C),
129.98 (C), 129.47 (CH), 128.37 (CH), 128.11 (C), 127.62
(CH), 126.31(CH), 125.52(CH), 124.07(CH), 123.24(CH),
121.10 (CH), 104.36 (CH), 81.20 (C), 43.50 (CH2), 28.26
(CH3). HR-MS (ESIþ) for C66H67N6O6 [M þ H]þ calcu-
lated: 1039.5117, found: 1039.5149.
2,4,6-Tris(bromomethyl)-N1,N1,N3,N3,N5,N5-hexakis(tert-
butoxycarbonyl)-2,4,6-trimethylbenzene-1,3,5-triamine (8)
Triamine 7 (0.50 g, 0.65 mmol) was treated with N-
bromosuccinimide (NBS, 0.42g, 2.36mmol) and a,a0-azo-
bis-isobutyronitrile (AIBN, 0.03g) in CCl4 (60 ml) under
irradiation by an IR lamp for 5 h. The reaction mixture was
evaporated to dryness in vacuo, and the residue was
separated by column chromatography (dichloromethane/
diethylether 25:1) to obtain 0.49g (74.9%) of tribromide 8.
1H NMR (CDCl3): d4.33 (6H, s), 1.45 (54H, s). 13C APT
NMR (CDCl3): d150.20 (C), 139.40 (C), 135.23 (C), 84.14
(C), 28.08 (CH3), 23.38 (CH2). HR-MS (ESIþ): for
C39H60Br3N3O12Na [M þ Na]þ calculated: 1024.1599,
1026.1578, 1027.1612, found: 1024.1598, 1026.1577,
1027.1598.
Procedure II
N1,N3,N5-tris(tert-butoxycarbonyl)-2,4,6-tris((naphtha-
len-2-ylamino)methyl)benzene-1,3,5-triamine(2a). Tribro-
mide
3
(350 mg, 498 mmol) was treated with
2-aminonaphthalene (430mg, 3003mmol) in 50ml of THF
at 508C for 5 h. The reaction mixture was alkalinised by
concentrated aq. NH3 (1 ml) in water (250ml). Chloroform
(50 ml) wasadded, organic partwas extractedbywater, dried
over Na2SO4, evaporated to dryness invacuo and the residue
was separated by column chromatography (toluene:ethyl
acetate 5:1) to obtain 222 mg (50.1%) of hexaamine 2a.
Preparation of hexaamines 2
N1,N3,N5-tris(tert-butoxycarbonyl)-2,4,6-tris((anthracen-
2-ylamino)methyl)benzene-1,3,5-triamine (2b). Tribro-
mide 3 (350 g, 498 mmol) was treated with 2-aminoan-
thracene (580 mg, 3001 mmol) in 50 ml of THF at 508C for
5 h. The reaction mixture was alkalinised by concentrated
aq. NH3 (1 ml) in water (250 ml). Chloroform (50 ml) was
added, organic part was extracted by water, dried over
Na2SO4, evaporated to dryness in vacuo and the residue
was separated by column chromatography (toluene:ethyl
acetate 5:1) to obtain 176 mg (34.0%) of hexaamine 2b.
Procedure I
N1,N3,N5-tris(tert-butoxycarbonyl)-2,4,6-tris((naphtha-
len-2-ylamino)methyl)benzene-1,3,5-triamine
(2a).
Tribromide 3 (250 mg, 356 mmol) was treated with 2-
aminonaphthalene (310 mg, 2165 mmol) and K2CO3
(110 mg, 796 mmol) in 40 ml of DMF at 508C for 2 h. The
reaction mixture was evaporated to dryness in vacuo, and
the residue was separated by column chromatography
(toluene:ethyl acetate 5:1) to obtain 130 mg (41.1%)
of hexaamine 2a. 1H NMR (CDCl3): d7.73 (3H, d, J ¼ 7.5),
7.70 (3H, d, J ¼ 8.8), 7.69 (3H, d, J ¼ 7.5), 7.49 (3H, bs),
7.42 (3H, dt, J ¼ 7.5, J ¼ 1.2), 7.27 (3H, dt, J ¼ 7.5,
J ¼ 1.2), 7.12 (3H, d, J ¼ 2.2), 7.05 (3H, dd, J ¼ 8.8,
J ¼ 2.2), 4.60 (3H, bs), 4.34 (6H, s), 1.37 (27H, s). 13C APT
NMR (CDCl3): d155.36 (C), 146.52 (C), 137.17 (C),
135.08 (C), 129.90 (C), 129.04 (CH), 128.53 (C), 127.79
(CH), 126.49 (CH), 126.36 (CH), 122.85 (CH), 119.21
(CH), 107.48 (CH), 81.04 (C), 44.03 (CH2), 28.31 (CH3).
HR-MS (ESIþ) for C54H61N6O6 [M þ H]þ calculated:
889.4647, found: 889.4636.
Preparation of tris-TB 1
Throne-1a. Hexaamine 2a (100 mg, 112 mmol) was
dissolved in 10 ml of TFA, and 64 mg of paraformaldehyde
(1332 mmol of CH2O equiv.) was added. The reaction
mixture was stirred at room temperature for overnight. The
reaction mixture was diluted with ice water, alkalinised by
concentrated aq. NH3 and extracted with dichloromethane.
The organic parts were extracted by water, dried over
Na2SO4, evaporated to dryness in vacuo and the residue
was separated by column chromatography (toluene:ace-
tone 3:1) to obtain 65 mg (87.5%) of throne-1a. 1H NMR
(CDCl3): d7.88–7.18 (18H, m), 4.90–4.51 (9H, m), 4.42–
3.92 (9H, m). 13C APT NMR (CDCl3): d145.49 (C),
145.37 (C), 145.10 (C), 144.71 (C), 144.67 (C), 144.50
N1,N3,N5-tris(tert-butoxycarbonyl)-2,4,6-tris((anthracen-
2-ylamino)methyl)benzene-1,3,5-triamine (2b). Tribro-
mide 3 (250g, 356 mmol) was treated with 2-aminoanthra-
cene (420mg, 2173mmol) and K2CO3 (110mg, 796 mmol)

Supramolecular Chemistry
133
(C), 131.48 (C), 131.32 (C), 131.00 (C), 130.93 (C),
130.87 (C), 130.71 (C), 128.79 (CH), 128.63 (CH), 128.53
(CH), 127.96 (CH), 127.94 (CH), 127.79 (CH), 126.63
(CH), 126.53 (CH), 126.35 (CH), 125.12 (CH), 124.90
(CH), 124.83 (CH), 124.73 (CH), 124.64 (CH), 124.14
(CH), 121.41 (C), 121.35 (C), 121.33 (C), 121.20 (CH),
121.14 (CH), 120.78 (CH), 119.13 (C), 118.32 (C), 118.20
(C), 66.90 (CH2), 66.85 (CH2), 66.68 (CH2), 55.31 (CH2),
54.22 (CH2), 54.18 (CH2), 53.94 (CH2), 53.03 (CH2),
53.01 (CH2). HR-MS (ESIþ) for C45H37N6 [M þ H]þ
calculated: 661.3074, found: 661.3077.
67.11 (CH2), 67.01 (CH2), 66.81 (CH2), 54.71 (CH2),
54.20 (CH2), 53.37 (CH2), 53.55 (CH2), 53.33 (CH2),
53.24 (CH2). HR-MS (ESIþ) for C57H43N6 [M þ H]þ
calculated: 811.3544., found: 811.3541.
X-ray crystallographic analysis of throne-1a
Suitable single crystal of throne-1a for single-crystal X-ray
diffraction was obtained by crystallisation from the mixture
of dichloromethane and methanol. The intensity data were
collected using a Bruker APEX-II CCD diffractometer.
Crystal data: C45H36N6·2(CH2Cl2), Mr ¼ 830.65, crystal
size: 0.58 £ 0.45 £ 0.37mm, colourless prism, triclinic,
Calix-1a. Throne-1a (100 mg, 151 mmol) was dis-
solved in acid mixture (5 ml of TFA and 5 ml of HBr). The
reaction mixture was stirred at 608C for 5 days. The
reaction mixture was diluted with ice water, alkalinised by
concentrated aq. NH3 and extracted with dichloromethane.
The organic parts were extracted by water, dried over
Na2SO4, evaporated to dryness in vacuo and the residue
was separated by column chromatography (toluene:ace-
tone 3:1) to obtain 4.0 mg (4.0%) of calix-1a and 94.8 mg
˚
space group: P-1 (No. 2), a ¼ 10.2949 (5) A, b ¼ 13.8180
˚
˚
(7) A, c ¼ 15.2560 (7) A, a ¼ 110.341 (2)8, b ¼ 102.153
3
˚
(2)8, g ¼ 94.045 (2)8, V ¼ 1964.70 (16) A , Z ¼ 2,
F000 ¼ 864, Dx ¼ 1.404 mg m 23, l ¼ 0.71073 A [Mo,
˚
Ka], u ¼ 2.2–27.58, m ¼ 0.35mm21, T ¼ 150 (2) K. Data
collection and refinement details: 66073 measured reflec-
tions, 9025 independent reflections, Rint ¼ 0.030, 7147
reflections with I . 2s(I), umax ¼ 27.58, umin ¼ 1.58,
R[F 2 . 2s(F 2)] ¼ 0.057, wR(F 2) ¼ 0.167, w ¼ 1/
[s2(Fo2) þ (0.091P)2 þ 1.2586P] where P ¼ (Fo2 þ 2F2c)/3,
1
(94.8%) of starting throne-1a. H NMR (CDCl3): d7.63
(3H, d, J ¼ 8.8), 7.59 (3H, dd, J ¼ 7.9, J ¼ 1.4), 7.38 (3H,
d, J ¼ 8.8), 7.33 (3H, dd, J ¼ 8.3, J ¼ 1.3), 7.29-7.15 (6H,
m), 4.82 (3H, d, J ¼ 17.5), 4.80 (3H, d, J ¼ 16.8), 4.58
(3H, d, J ¼ 17.5), 4.36 (3H, d, J ¼ 12.8), 4.32 (3H, d,
J ¼ 12.8), 3.99 (3H, d, J ¼ 16.8). 13C APT NMR (CDCl3):
d145.41 (C), 144.80 (C), 131.22 (C), 130.98 (C), 128.53
(CH), 127.98 (CH), 126.38 (CH), 124.63 (CH), 124.30
(CH), 121.20 (C), 120.98 (CH), 120.55 (C), 66.47 (CH2),
55.17 (CH2), 53.15 (CH2). HRMS (ESIþ) for C45H37N6
[M þ H]þ calculated: 661.3074, found: 661.3081.
-3
˚
S ¼ 1.07, (D/s)max ¼ 0.002, Drmax ¼ 0.84 eA ,
Drmin ¼ 20.86eA23. The contributions of the disordered
˚
second molecule of dichloromethanewere removed from the
diffraction data with PLATON/SQUEEZE procedure to
improve the precision of the main molecule (9). The number
of electrons removed from the voids was estimated as 97,
which corresponds to the two molecules of dichloromethane
in the unit cell. Crystallographic data for the structural
analysis have been deposited at the Cambridge Crystal-
lographic Data Centre (CCDC No. 847361). These data can
be obtained free of charge from the director, CCDC (http://
www.ccdc.cam.ac.uk/conts/retrieving.html).
Throne-1b. Hexaamine 2b (55 mg, 53 mmol) was
dissolved in 10 ml of TFA, and 30 mg of paraformaldehyde
(624 mmol of CH2O equiv.) was added. The reaction
mixture was stirred at room temperature for overnight. The
reaction mixture was diluted with ice water, alkalinised by
concentrated aq. NH3 and extracted with dichloromethane.
The organic parts were extracted by water, dried over
Na2SO4, evaporated to dryness in vacuo and the residue
was separated by column chromatography (toluene:ace-
tone 3:1) to obtain 11 mg (25.6%) of throne-1b. 1H NMR
(CDCl3): d8.35 (1H, s), 8.21–7.19 (23H, m), 5.01–4.56
(9H, m), 4.50–4.04 (9H, m). 13C APT NMR (CDCl3):
d144.87 (C), 144.79 (C), 144.77 (C), 144.72 (C), 144.45
(C), 144.29 (C), 132.07 (C), 131.91 (2 £ C), 130.92 (C),
130.75 (C), 130.71 (C), 129.93 (2 £ C), 129.76 (C), 129.59
(2 £ C), 129.55 (C), 128.38 (2 £ CH), 128.20 (2 £ CH),
128.14 (CH), 128.08 (CH), 128.02 (2 £ CH), 127.95 (CH),
127.29 (CH), 127.19 (CH), 126.97 (CH), 125.92 (CH),
125.71 (CH), 125.64 (CH), 125.37 (CH), 125.18 (CH),
125.09 (CH), 124.99 (CH), 124.95 (CH), 124.35 (CH),
120.45 (C), 120.42 (C), 120.39 (C), 119.12 (CH), 119.10
(C), 119.06 (CH), 118.87 (CH), 118.34 (C), 118.32 (C),
Diastereoisomerisation studies of tris-TB 1a
Throne-1a (5.0 mg, 7.6 mmol) was dissolved in 5 ml of
acid. The reaction mixture was stirred at 608C for 7 days
and samples (0.2 ml) were obtained in time intervals. The
sample was alkalinised by concentrated aq. NH3 and
extracted with dichloromethane. The organic parts were
dried over Na2SO4 and analysed by HPLC. The ratios of
diastereoisomers of tris-TB 1a and conditions (acid,
reaction time) are listed in Table 1.
Supplementary data
Supplementary data (1H and 13C APT NMR spectra) for all
presented compounds can be found in the online version.
Acknowledgement
This work was supported by the Grant Agency of the Czech
Republic (P207/11/P121).

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M. Havlık et al.
134
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(5) (a) Havlık, M.; Kral, V.; Dolensky, B. Collect. Czech. Chem.
References
´
Commun. 2007, 72, 392–402. (b) Havlık, M.; Kral, V.;
´
¨
(1) Troger, J. J. Prakt. Chem. 1887, 36, 225–245.
´
Kaplanek, R.; Dolensky, B. Org. Lett. 2008, 10, 4767–4769.
´
´
´
´
(2) (a) Dolensky, B.; Elguero, J.; Kral, V.; Pardo, C.; Valık, M.
Adv. Heterocycl. Chem. 2007, 93, 1–56. (b)Sergeyev, S. Helv.
Chim. Acta 2009, 92, 415–444.
(6) Risch, N. Chem. Ber. 1985, 118, 4849–4856.
´
ˇ ´
(7) (a) Valık, M.; Matejka, P.; Herdtweck, E.; Kral, V.;
´
(3) (a) Valık, M.; Dolensky, B.; Petrıckova H.; Kral, V. Collect.
Czech. Chem. Commun. 2002, 67, 609–621. (b) Valık, M.;
´
ˇ´ˇ
´
´
´
Dolensky, B. Collect. Czech. Chem. Commun. 2006, 71,
1278–1302. (b) Mas, T.; Pardo, C.; Elguero, J. Arkivoc 2004,
iv, 86–93. (c) Artacho, J.; Nilsson, P.; Bergquist, K.-E.;
´
ˇ
´
Cejka, J.; Havlık, M.; Kral, V.; Dolensky, B. Chem. Commun.
2007, 37, 3835–3837.
´
´
¨
Wendt, O.F.; Warnmark, K. Chem. Eur. J. 2006, 12, 2692–
2701. (d) Hansson, A.; Wixe, T.; Bergquist, K.-E.;
(4) (a) Szejtli, J. Chem. Rev. 1998, 98, 1743–1753. (b) Del Valle,
E.M.M. Proc. Biochem. 2004, 39, 1033–1046. (c) Sliwa, W.;
Kozlowski, C. Calixarenes and Resorcinarenes. Synthesis,
Properties and Applications, Wiley-VCH: Weinheim, 2009,
pp 1–316. (d) Lagona, J.; Mukhopadhyay, P.; Chakrabarti,
S.; Isaacs L. Angew. Chem. Int. Ed. 2005, 44, 4844–4870.
¨
Warnmark, K. Org. Lett. 2005, 7, 2019–2022.
(8) (a) Becke, A.D. J. Chem. Phys. 1993, 98, 5648–5652. (b)
Grimme, S.J. Comp. Chem. 2006, 27, 1787–1799.
(9) Spek, A.L. Acta Cryst. 2009, D65, 148–155.