Lacunar derivatives of dibenzotetraaza[14]annulene: Synthesis and crystal structure of new receptors produced via bis-alkylation of the macrocyclic precursor

Article abstract of DOI:10.1016/j.tet.2011.02.010

The bis(2-hydroxybenzoyl) derivative of dibenzotetraaza[14]annulene was employed as a substrate for producing new lacunar-type receptors. Alkylation of both phenolic OH groups using aliphatic dibromides and ditosylates efficiently leads to the expected br

Full text of DOI:10.1016/j.tet.2011.02.010

Tetrahedron 67 (2011) 2623e2632
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Lacunar derivatives of dibenzotetraaza[14]annulene: synthesis and crystal
structure of new receptors produced via bis-alkylation of the macrocyclic
precursor
a
a
a,
ꢀ b
*
ꢀ
Jaros1aw Grolik , Krzysztof Zwolinski , Les1aw Sieron , Julita Eilmes
a
ꢀ
Department of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland
Institute of General and Ecological Chemistry, Technical University of Łodz, Zeromskiego 116, 90-924 Łodz, Poland
b
_
ꢀ ꢀ
ꢀ ꢀ
a r t i c l e i n f o
a b s t r a c t
Article history:
The bis(2-hydroxybenzoyl) derivative of dibenzotetraaza[14]annulene was employed as a substrate for
producing new lacunar-type receptors. Alkylation of both phenolic OH groups using aliphatic dibromides
and ditosylates efficiently leads to the expected bridged products without recourse to a high dilution
procedure. Four new dibenzotetraaza[14]annulene-based lacunar receptors, and one unbridged open-
chain bis-octoxy analogue have been synthesized. Synthetic procedures, analytical and spectroscopic
characterization are reported. Conformations of the macrocyclic rings in the products as well as non-
covalent interactions are discussed on the basis of their crystal structures.
Received 28 October 2010
Received in revised form 13 January 2011
Accepted 1 February 2011
Available online 1 March 2011
Keywords:
Dibenzotetraaza[14]annulene
Lacunar macrocycle
Bis-alkylation
Ó 2011 Elsevier Ltd. All rights reserved.
Crystal structure
Non-covalent interactions
1. Introduction
serve as steric protection of the coordination axial sites preventing
autooxidation, which is known to occur through peroxo-dimeric
Lacunar macrocycles belong to the superstructured systems
containing a protected cavity in the vicinity of the metal co-
ordination site. They are produced by the modification of the
macrocyclic ligands through constructing bridges, which span
distant points on the macrocyclic core and are suspended above
a metal ion site. Since the bridging reactions with use of long di-
functional linkers often lead to more thermodynamically favour-
able oligomers and polymers, lacunar compounds are usually
synthesized using high dilution techniques.
Earlier studies on lacunar compounds and on similar more
complex superstructured systems were mainly focused on de-
rivatives of porphyrin,1 cyclidenes2 and of some Schiff-base com-
plexes.3 They were undertaken in the search for synthetic models of
natural heme proteins and resulted in preparation of efficient Co(II)
and Fe(II) reversible oxygen carriers.4
forms. They also allow controlling the hosteguest complexation,
important for enzyme-type catalytic activity, by suitable choice of
the cavity shape, size and binding properties.
In our previous paper6 we showed that dibenzotetraaza[14]
annulene 1 may be employed for efficient preparation of lacunar
macrocyclic receptors by formation of ester linkages involving OH
groups of the precursor 1. We also discussed the crystal structures
of the products pointing out important spatial relationships in the
molecules and suggesting the possible influence of non-covalent
self-assembling interactions on the relatively high yield of the
lacunization reaction.
In line with these results we report here the preparation and
crystal structures of new bridged receptors produced via alkylation
of OH groups of the ligands 1 and 2. The new products 3e7 con-
sidered in this paper are shown in Scheme 1. The bridging poly-
methylene chains in 4e6 contain five and 10 members; the product
7 has also a p-phenylene moiety built into the bridging tetraethoxy
linker. An open-chain analogue 3, bearing two pendant octoxy
substituents was also synthesized.
They were also employed to mimic catalytic properties of nat-
urally occurring metalloenzymes, such as monooxygenase cyto-
chrome P-450.5 The bridges designed for heme-protein models
Conformations of the macrocyclic core are discussed and non-
covalent interactions are examined based on the crystal structures
of the products 3e7.
* Corresponding author. Tel.: þ48 12 6632294; fax: þ48 12 6340515; e-mail
address: jeilmes@chemia.uj.edu.pl (J. Eilmes).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.02.010

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J. Grolik et al. / Tetrahedron 67 (2011) 2623e2632
OH
O
R
R
N
N
N
N
R
R
H
H
R=H
1
2
R=Cl
O
HO
Ts(OCH2CH2)2O(C6H4)O(CH2CH2O)2Ts
Br(CH2)7CH3
Br(CH2)5Br
Br(CH2)10Br
a
a
22
22
25
21
O
b
22
25
23
24
22
25
21
O
b
23
24
21
O
21
O
23
24
23
24
c
20
19
20
19
O
d
d
O
O
20
19
20
19
O
a
O
25
e
7
f
c
7
b
c
6
7
8
8
7
6
8
g
6
6
O
8
4
1
10
9
e
5 N
N
4
10
d
h
4
10
11
12
4
1
10
13
3
R
5 N
N9
e
R
R
11
12
5 N
N9
c
3
2
N 9
f
5 N
H
H
11
12
H
H
3
2
3
2
11
12
H
H
H
H
18 N
N14
R
2
18N
N14
13
18N
N14
13
1
O
16
18 N
N14
13
b
1
15
15
17
15
17
15
16
17
17
16
16
O
O
O
a
O
O
O
O
O
O
7
R=H
5
6
4
3
R=Cl
Scheme 1.
2. Results and discussion
2.1. Synthesis
formed by the bridges are therefore relatively large although the
linkers are fairly flexible.
The crystal structure revealing details of the spatial arrange-
ment within the hydroxybenzoyl parts of 1 has been reported
previously.8 Fig. 1 shows that the conformations of the molecules
3e7 depend significantly on the size and structure of the bridging
moieties and of the pending substituents introduced to the struc-
ture of 1.
The shape of the molecule 7 suggests attractive interactions
between the main macrocycle and a rigid p-phenylene ring in-
corporated into the bridge. A deformation of the macrocyclic core
occurs in 4, which have the shortest pentamethylene bridge,
whereas the open-chain bis-octoxy derivative 3 shows the more
relaxed conformation with the aliphatic chains folded above and
below the main macrocycle. Detailed discussion on the crystal
structure and on non-covalent interactions in the molecules 3e7
are given in Section 2.2.
The lacunar derivatives 4e7 were synthesized by bis-alkylation
of 1 and 2 with corresponding dibromides and ditosylates (Scheme
1). By varying the lengths of the reacting difunctional alkylating
reagents we have found that polymethylene chains shorter than
five members were too short to span the two bridging oxygen
positions in hydroxybenzoyl substituents of the precursors 1 and 2.
When dibromobutane and dibromopropane were used as alkylat-
ing reagents, the reaction led to corresponding 1:2 products, as
already reported.7
Although dibenzotetraaza[14]annulenes 1 and 2 are essentially
planar, causing lacunization to be less favourable, in our experi-
ments bridge closure across the whole molecule appeared rela-
tively facile. Reasonable yields of the bridged bis-alkylated
products, ranging from 64 to 83%, have been obtained without
recourse to a high dilution procedure. It seems that the 2-hydroxy-
benzoyl substituents of 1 and 2, freely rotating along CeC bonds,
offer favourable steric exposure of reacting OH centres and facili-
tate closure of the bridge. Moreover, as can be seen in the crystal
structures of the products 3e7, the phenyl rings in these moieties,
linked through ether oxygens to the polymethylene chains, are
almost perpendicular to the N4 plane (Fig. 1). As rigid parts of the
bridging linkers, they act as risers, which lift the bridge above the
coordination plane and prevent it from collapsing. The cavities
2.2. Crystallography
Crystal data and other parameters related to data collection for
all structures are summarized in Table 1. Molecular structures of the
products 3e7 are shown in Fig. 1.
2.2.1. Compound 3. Compound 3 (Fig. 2) crystallizes in the triclinic
Pꢀ1 space group with one half of the molecule in the asymmetric
part of the unit cell. The central 14-membered ring has a planar

J. Grolik et al. / Tetrahedron 67 (2011) 2623e2632
2625
Fig. 1. Two perpendicular views of the main molecules 3, 4, 5, 6 and 7.

2626
J. Grolik et al. / Tetrahedron 67 (2011) 2623e2632
Table 1
Crystal data and structural refinement details for 3, 4, 5, 6 and 7
3
4
5
6
7
Empirical formula
Formula weight
Crystal system
Space group
C48H56N4O4
752.97
Triclinic
Pꢀ1
C37H32N4O4 / CH2Cl2
681.59
Triclinic
Pꢀ1
C42H42N4O4
666.80
Triclinic
Pꢀ1
C42H38Cl4N4O4
804.56
Monoclinic
P21/n
15.7820 (7)
10.8248 (5)
22.3016 (10)
90
97.180 (1)
90
C46H42N4O8 / C3H7NO
Orthorhombic
Pccn
21.3884 (8)
13.6839 (5)
14.6694 (5)
90
ꢁ
a (A)
9.1198 (3)
9.2980 (3)
12.2327 (4)
82.174 (1)
81.287 (1)
77.132 (1)
993.90 (6), 1
1.258
8.4151 (3)
12.4787 (4)
16.1717 (5)
85.811 (1)
79.751 (1)
73.950 (1)
1605.44 (9), 2
1.410
10.9759 (2)
11.3673 (2)
14.7317 (3)
110.092 (1)
98.169 (1)
101.586 (1)
1645.88 (6), 2
1.345
ꢁ
b (A)
ꢁ
c (A)
a
b
g
(ꢁ)
(ꢁ)
(ꢁ)
90
90
3
ꢁ
V (A ), Z
3780.1 (3), 4
1.414
1672
4293.4 (3), 4
1.318
1800
dcalcd (g/cm3)
F (000)
404
712
708
Temperature (K)
100
Mo K
0.080
1.7e25.0
100
Mo K
0.252
1.7e25.0
90
Mo K
0.087
1.5e25.0
95
Mo K
0.363
1.5e25.0
92
Mo K
0.092
1.8e25.0
ꢁ
Radiation type, wavelength (A)
a
, 0.71073
a
, 0.71073
a
, 0.71073
a
, 0.71073
a, 0.71073
m
(mmꢀ1
)
Theta range (ꢁ)
Limiting indices, h, k, l
ꢀ10/10, ꢀ11/11,
ꢀ10/10, ꢀ14/14,
ꢀ13/13, ꢀ13/13,
ꢀ18/18, ꢀ12/12,
ꢀ25/25,
ꢀ14/14
ꢀ19/19
ꢀ17/17
ꢀ26/26
ꢀ16/16, ꢀ17/17
Reflections collected
Unique reflections
19,151
35,838
42,085
53,432
58,811
3777 [Rint¼0.024]
100.0%
3495 [Rint¼0.015]
5635 [Rint¼0.018]
5786 [Rint¼0.021]
6653 [Rint¼0.025]
Completeness to
q
¼25.00ꢁ
99.9%
99.9%
100.0%
100.0%
Data/restraints/parameters
3495/0/259
1.031
5635/0/442
1.040
5786/0/460
1.053
6653/0/495
1.070
3777/0/367
1.088
Goodness-of-fit on F2
Final R indices [I>2
Final R indices [all data]
Largest diff. peak and hole (e A
s
(I)]
R¼0.0303, wR2¼0.0822
R¼0.0316, wR2¼0.0833
0.25, ꢀ0.17
R¼0.0280, wR2¼0.0733
R¼0.0301, wR2¼0.0746
0.26, ꢀ0.33
R¼0.0302, wR2¼0.0808
R¼0.0322, wR2¼0.0822
0.24, ꢀ0.20
R¼0.0285, wR2¼0.0747
R¼0.0330, wR2¼0.0775
0.95, ꢀ0.37
R¼0.0475, wR2¼0.1411
R¼0.0516, wR2¼0.1450
0.46, ꢀ0.35
ꢁꢀ3
)
Compound 3: weight¼1/[
Compound 4: weight¼1/[
Compound 5: weight¼1/[
Compound 6: weight¼1/[
Compound 7: weight¼1/[
s
s
s
s
s
2(Fo2)þ(0.0424P)2þ0.3259P] where P¼(Fo2þ2F2c)/3.
2(Fo2)þ(0.0359P)2þ0.7614P] where P¼(Fo2þ2F2c)/3.
2(Fo2)þ(0.0413P)2þ0.5876P] where P¼(Fo2þ2F2c)/3.
2(Fo2)þ(0.0368P)2þ1.8719P] where P¼(Fo2þ2F2c)/3.
2(Fo2)þ(0.0881P)2þ2.3554P] where P¼(Fo2þ2F2c)/3.
Fig. 2. An ORTEP view of 3 with numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. Unlabelled atoms are related to labelled atoms by the symmetry
code ꢀxþ1, ꢀyþ1, ꢀzþ2. Hydrogen atoms are drawn with an arbitrary radius.
ꢁ
conformation and lies across the centre of inversion. The macro-
cyclic ring is, however, not planar, and its distortion from planarity
is up to 0.128 (1) A for the N1 atom.
contact with C(17)/centroid distance of 3.6315 (12)
A
and
C19eH19A/C1xꢀ1, y, z distance of 2.990 A. Consequently, the chains
can adopt a nearly planar fully extended anti-periplanar confor-
mation with torsion angles of C17eC18eC19eC20¼177.0 (1),
C18eC19eC20eC21¼176.4 (1), C19eC20eC21eC22¼178.8 (1),
C20eC21eC22eC23¼176.7 (1) andC21eC22eC23eC24¼177.3 (1)ꢁ.
Moreover, the plane formed by aliphatic carbons is almost parallel
ꢁ
ꢁ
The ring has two open aliphatic chains folded above and below
the adjacent tetraaza macroring with an approximate distance of
ꢁ
3.7 A. There are no significant CeH/
p chain-plane interactions,
except the weak intermolecular C(17)eH(17B)/C(2e7)xꢀ1, y, z ring

J. Grolik et al. / Tetrahedron 67 (2011) 2623e2632
2627
to the tetraaza one with the dihedral angle between them of 3.37
(7)ꢁ. The dihedral angle between planes of benzoyl and tetraaza
rings is 63.03 (2)ꢁ.
2.2.2. Compound 4. The lacunar compound 4 (Fig. 4) crystallizes in
the triclinic Pꢀ1 space group and contains two macrocyclic mole-
cules and two dichloromethane solvent molecules in the asym-
metric part of the unit cell.
The aliphatic chain in 4 is distinctly folded above the tetraaza
ring and adopts a conformation defined by six torsion angles:
C16eO2eC17eC18¼178.5 (1), O2eC17eC18eC19¼78.2 (1),
C17eC18eC19eC20¼e158.2 (1), C18eC19eC20eC21¼e161.4 (1),
C19eC20eC21eO3¼ꢀ169.7 (1) and C20eC21eO3eC22¼179.7 (1),
which corresponds to descriptors þap/þsc/ꢀap/þap/ꢀap/þap.
A short 5-carbon-membered aliphatic chain causes tension in
the molecule and a deformation of the tetraaza macroring from
planarity. In effect the ring adopts a significantly basket-like shaped
As for intermolecular interactions, the molecules of the macro-
cycle have carbonyl oxygen atoms able to form hydrogen bonds. Since
the only hydrogen donors accessible for intermolecular interactions
are carbon atoms, weak CeH/O hydrogen bonds can be utilized to
assemble the molecules. The carbonyl oxygens from the keto groups
form here bifurcated hydrogen bonding with H(1) and H(3) atoms of
the tetraazamacrocycles, assembling neighbouring molecules into
coplanar chains (Table 2, Fig. 3). There is no evidence of significant
p/p interactions between benzene rings in the structure.
conformation. The minimal distance between aliphatic chain and
Table 2
ꢁ
ꢁ
ꢁ
Close contacts of hydrogen bond type [A,
]
the tetraaza ring of CeH/
nificant interactions.
p¼3.4 A is, however, too long for sig-
DeH/A
H/A
D/A
DeH/A
The carbonyl oxygens from the keto groups form different in-
3
C(3)eH(3)/O(1)ꢀ1þx, 1þy, z
C(17)eH(17B)/Cg(1)
Cg(1)¼centroid C(2e7)
2.58
2.86
3.4948 (13)
3.6315 (12)
163
135
termolecular CeH/O hydrogen bonding. The O(1) atom interacts
with H(5)3ꢀx,ꢀy, 1ꢀz of benzene ring with distance of 2.57 A, and the
ꢁ
O(4) atom is involved in bifurcated hydrogen bonding with H(1)
and H(32) atoms of the tetraazamacrocycle and benzene rings,
4
respectively (Table 2).
C(1)eH(1)/O(4)3ꢀx, ꢀy, ꢀz
C(5)eH(5)/O(1)3ꢀx, ꢀy, 1ꢀz
C(32)eH(32)/O(4)2ꢀx, ꢀy, ꢀz
2.50
2.57
2.47
3.420 (2)
3.173 (2)
3.300 (2)
162
122
146
ꢁ
The intermolecular
p
/p
contact of 3.7555 (7) A between C
(2e7) and C(31e36)1þx, y, z benzene rings is also observed.
5
2.2.3. Compounds 5 and 6. The lacunar compound 5 and its chloro-
substituted analogue 6 contain 10-carbon-membered aliphatic
chains (Figs. 5 and 6), thus the molecules can be more relaxed
than 4.
The overall conformation of the aliphatic chains is defined by 11
torsion angles with descriptors corresponding to the atom order
from C(16) to C(27) of ap/sc/ac/ap/ap/ap/ap/ap/sc/sc/sc and ap/sc/
ap/ap/ap/ap/ap/ap/sc/ac/ap for 5 and 6, respectively.
C(3)eH(3)/O(1)x, 1þy, z
C(18)eH(18B)/O(4)1ꢀx, 1ꢀy, 2ꢀz
C(40)eH(40)/O(4)x,ꢀ1þy, z
C(42)eH(42)/O(4)x, ꢀ1þy, z
C(17)eH(17A)/Cg(1)1ꢀx, ꢀy, 2ꢀz
C(24)eH(24A)/Cg(2)1ꢀx, ꢀy, 2ꢀz
2.36
2.56
2.40
2.57
2.90
2.96
3.3084 (15)
3.4350 (15)
3.3265 (15)
3.5098 (14)
3.7054 (13)
3.7891 (14)
172
147
165
173
139
141
Cg(1)¼centroid C(36e41); Cg(2)¼centroid C(11e16)
6
C(15)eH(15)/O(5)1/2þx, 3/2ꢀy, 1/2þz
C(23)eH(23B)/O(6)
2.44
2.59
2.41
3.186 (2)
3.211 (2)
3.000 (2)
135
121
120
A slight slope of the C18eC25 fragment of the aliphatic chain
plane in respect to 14-membered macrocyclic tetraaza plane of
about 22ꢁ in 5 arises probably from attractive intramolecular
C(31)eH(31)/O(10)ꢀ1/2þx, 1/2ꢀy, ꢀ1/2þz
C
sp3eH/p contacts with the NeC and CeC bonds of the tetraaza
7
ꢁ
ring: C(19)eH(19B)/[N2eC8]mid-point of 2.88 A and C(23)eH
(23A)/[C34eC35]mid-point of 2.86 A.
C(4)eH(4)/O(1)1ꢀx, 1/2þy, 1/2ꢀz
C(15)eH(15)/O(1)1ꢀx, ꢀy, ꢀz
C(18)eH(18B)/O(4)
2.33 (2)
2.59 (2)
2.29 (2)
2.66 (2)
2.77
3.230 (2)
3.526 (2)
3.044 (3)
3.543 (2)
3.724 (4)
165 (2)
ꢁ
154.4 (17)
127.9 (17)
149.5 (16)
164
In 6 the analogous fragment of the aliphatic chain is almost
C(5)eH(5)/Cg(1)1ꢀx, 1/2þy, 1/2ꢀz
C(32)eH(32A)/Cg(1)ꢀ1/2þx, 1/2þy, 1ꢀz
Cg(1)¼centroid C(11e16)
perpendicular (86ꢁ) to the macrocyclic tetraaza plane. Moreover,
the aliphatic chain is shifted aside by about 2 A with respect to the
macroring centre. Consequently, there are three intramolecular
ꢁ
Fig. 3. A perspective view of two neighbouring molecules of 3 connected by bifurcated CeH/O hydrogen bonds.

2628
J. Grolik et al. / Tetrahedron 67 (2011) 2623e2632
Fig. 4. An ORTEP view of main molecule of 4 with numbering scheme. displacement. ellipsoids are drawn at the 30% probability level. Hydrogen atoms are drawn with an arbitrary
radius. The dichloromethane molecule has been omitted.
Fig. 5. ORTEP views of 5 and 6 with numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. Hydrogen atoms are drawn with an arbitrary radius.
contacts of the type Csp3eH/[NeC]mid-point, ranging from 2.86 to
one half of the dimethylformamide solvent molecule in the asym-
metric part of the unit cell.
The benzene ring located in the middle of a lacunar chain causes
an attractive intramolecular interaction, approaching the centre of
the tetraaza ring.
ꢁ
ꢁ
3.08 A, below the 3.14 A limit, which can be considered still as an
attractive interaction.9
A near-parallel arrangement of the aliphatic chain with respect
to the tetraaza plane in 5 induces macroring deformation, which is
not observed in 6. This dependence has been previously reported in
lacunar-type derivatives of dibenzotetraaza[14]annulene.6
The dihedral angles between planes of benzoyl and tetraaza
rings [C(11e16) and C(27e32)] in 5 of 66.50 (3) and 61.72 (2)ꢁ are
more equalized than the respective angles of 54.71 (4) and 77.18
(3)ꢁ in 6.
The distances between the neighbouring symmetry-
1/2ꢀy,
related parallel benzene ring and N(1)eN(2)eN(1)3/2ꢀx,
ze
ꢁ
N(2)3/2ꢀx, 1/2ꢀy, z planes are 3.584 A (intramolecular) and 3.751 A
(intermolecular). The conformation of the tetraaza ring becomes
significantly basket shaped. Its bending, described by dihedral an-
gle between two NeCeCeCeN planes, is 47.2ꢁ.
ꢁ
The molecules assemble into columns oriented along the c-axis
(Fig. 8). The adjacent columns are connected together by C(4)eH
2.2.4. Compound 7. Compound 7 (Fig. 7) crystallizes in the ortho-
rhombic Pccn space group with one half of the main molecule and
(4)/O(1)carbonyl, C(15)eH(15)/O(1)carbonyl and C(5)eH(15)/C

J. Grolik et al. / Tetrahedron 67 (2011) 2623e2632
2629
Fig. 6. ORTEP views of 5 and 6 with numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. Hydrogen atoms are drawn with an arbitrary radius.
Fig. 7. An ORTEP view of main molecule of 7 with numbering scheme. Displacement ellipsoids are drawn at the 30% probability level. Hydrogen atoms are drawn with an arbitrary
radius. The dimethylformamide molecule has been omitted.
(11e16) interactions. Between these columns channels are formed
inside, which solvent dimethylformamide molecules are located
(Fig. 8b).
Table 3. The hydrogen bonds are relatively long [ranging from
1.98 to 2.07 A] with small DeH/A angles [range: 133e138 ].
ꢁ
ꢁ
3. Conclusions
2.2.5. N4 planesegeometry of the hydrogen bonds. The positions of
the hydrogen atoms connected to the nitrogen atoms and par-
ticipating in the intermolecular hydrogen bonds were located
from the experimental difference electron density maps.
Details of hydrogen bonds present in the structures are given in
The bis-alkylation of the phenolic OH groups in dibenzotetraaza
[14]annulene ligands 1 and 2 using aliphatic dibromides or dito-
sylates allowed the synthesis of new lacunar receptors in respect-
able yields. The crystal structures show that the conformations of

2630
J. Grolik et al. / Tetrahedron 67 (2011) 2623e2632
Fig. 8. (a) A mutual orientation of the neighbouring molecules of 7. (b) The crystal packing of 7, showing molecules with channels running along c-axis.
1,5-Dibromopentane and 1,10-dibromodecane were purchased
Table 3
from commercial sources (SigmaeAldrich) and were used as re-
ꢁ
ꢁ
Intermolecular hydrogen-bonding geometry [A and
]
ceived. Solvents were dried using standard methods and were
freshly distilled before use. Elemental analyses were performed on
a Euro-EA (EuroVector) microanalyzer. 1H and 13C NMR spectra
were run on a Bruker AMX (500 MHz) spectrometer. Chemical
DeH/A
DeH
H/A
D/A
DeH/A
3
N(1)eH(1N)/N(2)1ꢀx, 1ꢀy, 2ꢀz
0.88 (1) 2.05 (1) 2.7516 (12) 136.3 (12)
4
shifts (d) are expressed in parts per million and J values in hertz.
Signal multiplicities are denoted as s (singlet), d (doublet), t (trip-
let), q (quartet) and m (multiplet). ESI and MALDI-TOF mass spectra
were taken on Esquire 3000 and Bruker Reflex IV spectrometers,
respectively. The IR spectra were recorded in KBr with a Bruker IFS
48 spectrophotometer. Melting points were measured using
a Boethius apparatus and are uncorrected.
N(1)eH(1N)/N(3)
N(4)eH(4N)/N(2)
5
0.87 (1) 2.00 (2) 2.6933 (16) 136.5 (14)
0.86 (1) 1.98 (2) 2.6810 (16) 138.0 (15)
N(1)eH(1N)/N(3)
N(4)eH(4N)/N(2)
6
0.90 (2) 2.03 (2) 2.7446 (13) 135.6 (14)
0.87 (2) 2.04 (1) 2.7381 (13) 136.1 (13)
4.2. Syntheses
N(1)eH(1N)/N(3)
N(4)eH(4N)/N(2)
7
0.90 (2) 2.07 (2) 2.7583 (17) 133.3 (16)
0.88 (2) 2.06 (2) 2.7579 (17) 135.2 (16)
4.2.1. 2,3,11,12-Tetrachloro-7,16-bis(2-hydroxybenzoyl)-5,14-dihy-
drodibenzo[b,i][1,4,8,11]tetraazacyclotetradecine (2). A solution of
4,5-dichloro-o-phenylenediamine (0.0354 g, 0.2 mmol) in dime-
thylformamide (1 mL) was added to the solution prepared by dis-
solving3-formylchromone(0.348g, 0.2mmol)indimethylformamide
(1 mL). The reaction mixture was stirred for 30 min at room temper-
ature. The orange-red microcrystalline product was collected by fil-
tration, washed with ethanol (15 mL) and dried under vacuum. The
fairly insoluble 2 was next used without further purification.
N(1)eH(1N)/ N(2)3/2ꢀx, 1/2ꢀy, z 0.81 (2) 2.00 (2)
2.662 (2)
137.8 (18)
the macrocyclic ring in the products are remarkably influenced by
the size and structure of the bridging linkers. A number of non-
covalent intra- and inter-molecular interactions were identified in
the crystal structures of the products.
The results reported here and in the previous paper6 show that
the 7,16-bis(2-hydroxybenzoyl) derivative of dibenzotetraaza[14]
annulene ligand can be very useful as a substrate for the prepara-
tion of various purpose-designed superstructured macrocycles,
important in the study of molecular recognition processes.
Orange-red powder, yield 32.5 mg (48.7%), mp>260 ꢁC. 1H NMR
(500 MHz; DMF-d7;
d
ppm): 7.07 (d, J¼8.4 Hz, 2H, H22), 7.48 (dd,
J¼8.4, 8.4 Hz, 2H, H23), 7.81 (s, 4H, H1,4,10,13), 7.87 (d, J¼7.75 Hz, 2H,
H
25), 8.75 (d, J¼6.4 Hz, 4H, H6,8,15,17), 10.94 (s, 2H, C21O-H), 14.21 (t,
J¼6.75 Hz, 2H, H5,14); 13C NMR (HSQC; DMF-d7;
d
ppm): 117 (C22);
118 (C1,4,10,13); 122 (C22); 123 (C23); 127 (C25); 154 (C6,8,15,17); IR
(ATR) nmax (cmꢀ1): 3063, 1632, 1557, 1477; MALDI-MS (m/z): 665.3
Mþ1 (C32H20Cl4N4O4). Anal. Calcd for C32H20Cl4N4O4: C, 57.68; H,
3.03; N, 8.41. Found: C, 57.51; H, 3.19; N, 8.54%.
4. Experimental
4.1. General
The macrocyclic substrate 7,16-bis(2-hydroxybenzoyl)-5,14-
dihydrodibenzo[b,i][1,4,8,11]tetraazacyclotetradecine (1) was pre-
pared by the procedures described earlier.10 1,4-Bis[2-(2-hydroxy-
ethoxy)ethoxy]benzene bis(4-methylbenzenesulfonate) was syn
thesized according to the reported procedure.11
4.2.2. Compounds 3e7 (general procedure). A reaction mixture
consisting of the substrate 1 or 2 (0.19 mmol), anhydrous potassium
carbonate (0.5 g) and the corresponding dibromide or tosylate
(0.3 mmol) in anhydrous dimethylformamide (75 mL) was heated
with stirring for 5 h at 80 ꢁC. It was next cooled to room

J. Grolik et al. / Tetrahedron 67 (2011) 2623e2632
2631
temperature and transferred to a separatory funnel. The mixture
was partitioned between chloroform (2ꢂ100 mL) and water
(2ꢂ100 mL). The combined organic solutions were washed with
water (3ꢂ100 mL), dried over anhydrous magnesium sulfate and
evaporated to dryness in a rotary evaporator. The residue was
chromatographed on a column of silica gel. The main orange frac-
tion was collected, concentrated to a small volume and left aside for
crystallization.
104.2 111.6 111.9 113.8 116.5121.5128.7 129.9 130.0 132.3 136.0 152.6
(C1e4,5a,9a,10e13,14a,18a,20e25), 155.9 (C6,8,15,17); 197.1 (C19); IR (KBr) nmax
(cmꢀ1): 3102, 3073, 3003, 2922, 2850, 1657, 1614, 1561; MALDI-MS
(m/z): 802.14 Mþ1 (C42H38Cl4N4O4). Anal. Calcd for C42H38Cl4N4O4: C,
62.70; H, 4.76; N, 6.96. Found: C, 62.54; H, 4.67; N, 6.88%.
4.2.2.5. Lacunar compound 7. Eluent: chloroform. Orange crys-
tals, yield 0.097 (66%). Crystals suitable for X-ray measurements
were prepared by slow diffusion of water into the solution of 7 in
4.2.2.1. 7,16-Bis[2-(octoxy)benzoyl]-5,14-dihydrodibenzo[b,i]
[1,4,8,11]tetraazacyclotetradecine (3). Eluent: dichloromethane. Red
crystals, yield 0.126 g (89%), mp¼135e136 ꢁC. Crystals suitable for
X-ray measurements were prepared by slow diffusion of diethyl
ether into the solution of 3 in dimethylformamide. 1H NMR
dimethylformamide. 1H NMR (500 MHz; CDCl3;
d ppm): 3.79 (s, 8H,
H
H
H
b,c), 3.90 4.22 (m, 4þ4H, Ha,d), 6.34 (s, 4H, Hf), 6.90e7.20 (m, 12H,
1e4,10e13), 7.36 (d, J¼8.0 Hz, 2H, H25), 7.48 (dd, J¼7.5, J¼7.5 Hz, 2H,
24), 7.26 (dd, J¼1.6, J¼7.6 Hz, 2H, H25), 7.41 (ddd, J¼7.6, 7.6, 1.6 Hz,
2H, H23), 8.53 (s, 4H, H6,8,15,17), 14.19 (t, J¼6.3 Hz, 2H, H5,14); 13C NMR
(500 MHz; CDCl3;
d
ppm): 0.75 (t, J¼6.9 Hz, 6H, Hh),1.0e1.2 (m,16H,
(125 MHz; CDCl3; d
ppm): 67.7, 68.6, 69.3, 69.9 (Caed); 110.3, 111.7,
H
deg), 1.29 (m, 4H, Hc), 1.65 (m, 4H, Hb), 3.98 (t, J¼6.4 Hz, 4H, Ha),
114.7, 115.1, 115.3, 115.9, 121.2, 126.4, 129.1, 129.6, 130.9, 137.3, 152.4,
153.3 (C 1e4,10e13,20e25,e,f),155.2 (C6,8,15,17); 192.9 (C19); IR (HCB) nmax
(cmꢀ1): 3440, 3060, 2926, 2875, 2856, 1670, 1645, 1597; ESI-MS (m/
z): 779.4 Mþ1 (C46H43N4O8). Anal. Calcd for C46H42N4O8: C, 70.94; H,
5.44; N, 7.19. Found: C, 70.63; H, 5.31; N, 7.02%.
6.98 (d, J¼8.3 Hz, 2H, H22), 7.05 (ddd, J¼0.6, 7.4, 8.3 Hz, 6H, H24),
7.07 (dd, J¼3.4, 6.1 Hz, 4H, H2,3,11,12), 7.16 (dd, J¼3.4, 6.1 Hz, 4H,
H
1,4,10,13), 7.38 (dd, J¼7.4,1.8 Hz 2H, H22), 7.43 (ddd, J¼1.8, 7.4, 7.4 Hz,
6H, H24), 8.58 (s, 4H, H6,8,15,17), 14.41 (br s, 2H, H5,14); 13C NMR
(125 MHz; CDCl3;
d
ppm): 13.9 (Cc); 22.5 25.9 29.1 29.2 (Cceg), 31.7
(Cd), 68.7 (Ca), 110.7 (C20), 112.3 (C22), 115.3 (C1,4,10,13), 120.9 (C24),
126.3 (C2,3,11,12), 129.5, 129.6, 131.2 (C7,16,23,25), 137.1 (C5a,9a,14a,18a),
152.8 (C 6,8,15,17), 155.9 (C21), 193.0 (C19); IR (HCB) nmax(cmꢀ1): 3462,
3064, 2928, 2852, 1652, 1593, 1562; MALDI-MS (m/z): 752.35 Mþ
(C48H56N4O4). Anal. Calcd for C48H56N4O4: C, 76.56; H, 7.50; N, 7.44.
Found: C, 76.41; H, 7.37; N, 7.40%.
5. Crystallography
Structures of the compounds 3, 4, 5, 6 and 7 were determined by
single-crystal X-ray diffraction. Intensity data were collected using
a Bruker AXS Smart APEX-II CCD 3-circle diffractometer with
MonoCap capillary and graphite-monochromated Mo K
a
radiation
¼0.71073 A, 50 kV, 32 mA) at 92e100 K. 2700 frames were
measured at 0.3ꢁ
-scans. Data collection and data reduction were
ꢁ
(l
4.2.2.2. Lacunar compound 4. Eluent: chloroform. Orange crys-
tals, yield 0.080 g (71%), mp>260 ꢁC. Crystals suitable for X-ray
measurements were grown from dichloromethane. 1H NMR
u
done with the SMART12 and SAINT-PLUS programs.13
The structures were solved by direct methods by using the
SHELXS-97 program.14 All non-hydrogen atoms were refined an-
isotropically by full-matrix least-squares based on F2 using the
SHELXL-97 program,14 and the complete set of reflections. The final
geometrical calculations were carried out with the PLATON pro-
gram.15 The relevant crystal data and experimental details are
summarized in Table 1. Except for freely refined nitrogen-con-
nected hydrogens, hydrogen atoms were placed in calculated po-
sitions and refined using a riding model.
(300 MHz, CDCl3, d
ppm): 1.24 (m, 2H, Hc), 1.53 (m, 4H, Hb), 3.74 (t,
4H, 3J¼6.4 Hz, Ha), 6.88 (dd, J¼0.6, 8.3 Hz, 2H, H22), 7.09e7.18 (m,
10H, H1e4,10e13,24), 7.42, (ddd, J¼1.8, 7.4, 9.2 Hz, 2H, H23), 7.57 (dd,
J¼1.7, 7.5 Hz, 2H, H25), 8.43 (d, J¼6.5 Hz, 4H, H6,8,15,17), 14.35 (t,
J¼6.5 Hz, 2H, HeN5,14); 13C NMR (75 MHz, CDCl3,
d
ppm): 21.6 (Cc),
29.8 (Cb), 68.5 (Ca), 111.4, 113.3, 116.2, 121.7, 126.5, 129.7, 130.4, 131.9,
138.0, 153.8, 156.5, 192.6 (C19); IR (KBr) nmax (cmꢀ1): 3457, 3061,
2945, 2869, 1646, 1613, 1597. ESI-MS (m/z): 597.4 (Mþ1)þ, 681,5
(MþCH2Cl2)þ. Anal. Calcd for C37H32N4O4. CH2Cl2: C, 66.96; H, 5.03;
N, 8.22. Found: C, 66.96; H, 4.99; N, 8.21%.
Figures were drawn using the Mercury16 and SHELXTL13
programs.
4.2.2.3. Lacunar compound 5. Eluent: chloroform. Red crystals,
yield 0.105 g (83%), mp¼298e300 ꢁC. Crystals suitable to X-ray
measurements were grown from chloroform. 1H NMR (300 MHz;
6. Crystallographic data
Crystallographic data for the structures reported in this paper
have been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication no. CCDC 798422 (compound
3), CCDC 798423 (compound 4), CCDC 798424 (compound 5), CCDC
798425 (compound 6), CCDC 798426 (compound 7). Copies of the
data can be obtained free of charge on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK (fax: (þ44) 1223 336 033;
e-mail: deposit@ccdc.cam.ac.uk).
CDCl3;
d
ppm): 0.97 (m, 4H, He), 1.08 (m, 4H, Hd), 1.23 (m, 4H, Hc),
1.59 (m, 4H, Hb), 3.96 (t, J¼5.3 Hz, 4H, Ha), 6.97 (d, J¼8.6 Hz, 2H,
H
H
22), 7.05e7.12 (m, 6H, H2,3,11,12,24), 7.16 (dd, J¼3.4, 6.1 Hz, 4H,
1,4,10,13), 7.30e7.50 (m, 4H, H23,25), 8.47 (s, 4H, H6,8,15,17), 14.30 (t,
J¼6.75 Hz, 2H, H5,14); 13C NMR (75 MHz; CDCl3;
d
ppm): 26.7 (Cc),
29.8, 29.9 (Cb,e), 30.3 (Cd), 68.6 (Ca), 110.9 (C20), 111.7 (C22), 114.8
(C1,4,10,13), 121.8 (C24), 126.2 (C2,3,11,12), 129.5 (C7,16), 129.7 (C25), 131.5
(C23), 136.3 (C5a,9a,14a,18a), 152.3 (C6,8,15,17), 155.9 (C21), 193.1 (C19); IR
(KBr) nmax(cmꢀ1): 3462, 3064, 2928, 2852, 1652, 1593, 1562;
MALDI-MS (m/z): 666.34 Mþ (C42H42N4O4). Anal. Calcd for
C42H42N4O4: C, 75.65; H, 6.35; N, 8.40. Found: C, 75.54; H, 6.31; N,
8.32%.
Acknowledgements
The research was carried out with the equipment purchased
thanks to the financial support of the European Regional De-
velopment Fund in the framework of the Polish Innovation
Economy Operational Program (contract no. POIG.02.01.00-12-
023/08).
4.2.2.4. Lacunar compound 6. Eluent: chloroform. Orange-red
crystals, yield 0.089 g (64%), mp>270 ꢁC. Crystals suitable to X-ray
measurements were grown from chloroform. 1H NMR (300 MHz;
CDCl3; d
ppm): 0.99 (m, 4H, He),1.11 (m, 4H, Hd),1.21 (m, 4H, Hc),1.63
(m, 4H, Hb), 3.95 (t, J¼5.3 Hz, 4H, Hc), 6.99 (d, J¼8.6 Hz, 2H, H22), 7.11
Supplementary data
(dd, J¼5.7, 5.7 Hz, 2H, H24), 7.21 (s, 4H, H1,4,10,13), 7.45e7.55 (m, 4H,
H
23,25), 8.45 (d, J¼6.6 Hz, 4H, H6,8,15,17), 14.13 (t, J¼6.75 Hz, 2H, H5,14);
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2011.02.010.
13CNMR(75MHz;CDCl3; ppm):26.829.8,29.930.3(Cbee),68.9(Ca),
d

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J. Grolik et al. / Tetrahedron 67 (2011) 2623e2632
5. (a) Feiters, M. C.; Rowan, A. E.; Nolte, R. J. M. Chem. Soc. Rev. 2000, 29, 375; (b)
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