Tetranitroresorcin[4]arene: synthesis and structure of a new stereoisomer

Article abstract of DOI:10.1016/j.tetlet.2009.10.075

The direct reaction between 2-nitroresorcinol and acetaldehyde in alkaline medium yields tetranitro-C₁-resorcin[4]arene in a moderate 8.2% overall yield which was characterized by single crystal X-ray crystallography, ¹H NMR spectros

Full text of DOI:10.1016/j.tetlet.2009.10.075

Tetrahedron Letters 50 (2009) 7369–7373
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Tetrahedron Letters
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Tetranitroresorcin[4]arene: synthesis and structure of a new stereoisomer
*
N. Kodiah Beyeh, Kari Rissanen
NanoScience Center, Department of Chemistry, University of Jyväskylä, PO Box 35, 40014 Jyväskylä, Finland
a r t i c l e i n f o
a b s t r a c t
Article history:
The direct reaction between 2-nitroresorcinol and acetaldehyde in alkaline medium yields tetranitro-C1-
resorcin[4]arene in a moderate 8.2% overall yield which was characterized by single crystal X-ray crys-
tallography, 1H NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS). In solution
and in the solid state, the product adopts a unique, thermally stable and unprecedented rcct-boat
conformation.
Received 25 August 2009
Revised 5 October 2009
Accepted 16 October 2009
Available online 22 October 2009
Ó 2009 Elsevier Ltd. All rights reserved.
The Cx-resorcin[4]arenes (x ꢀ 1) are typically prepared under
reflux conditions in alcoholic acidic medium of resorcinol and ali-
phatic or aromatic aldehydes.1 Substitution of resorcinol at posi-
tion 2 with an electron-withdrawing group such as a nitro group
deactivates the phenyl ring and it is generally accepted1 that the
acid and Lewis acid-catalyzed condensation reactions do not lead
to the cyclic oligomers due to the effective quenching of the reac-
tion after the formation of the dimer 1 (Scheme 1). Yet, under alka-
line conditions from 0 °C to room temperature, it has been shown
that the more reactive paraformaldehyde and 2-nitroresorcinol do
form a cyclic tetramer in high yield.2
A series of new structures that adopt specific geometry and
shapes have been reported previously. Amongst these compounds
are resorcin[4]arenes and pyrogall[4]arenes1 which usually adopt
the crown conformation and act as hosts for a range of guest spe-
cies.3 Resorcin[4]arenes also act as building blocks in the synthesis
of a wide variety of materials such as metal complexing agents4
and have been useful hosts for open inclusion complexes,5a–f di-
mers,5g,h hexamers5i–k and tubular assemblies.5l
same oligomers, but in slightly lower yields. In all cases, an in-
crease in temperature to 100 °C did not improve the yield.
The 1H NMR spectrum of the crude product in DMSO-d6 at
303 K confirmed a mixture of the dimer and the three cyclic oligo-
mers, the tetramer 2 being most abundant as highlighted in Figure
1. To shed light on the nature of the complexity of the reaction
products, an electrospray ionization mass spectrometric (ESI-MS)
study was performed, the result of which showed the mixture to
consist of the dimer 1 and cyclic oligomers, that is, tetramer 2, pen-
tamer 3 and hexamer 4 (Fig. 2, bottom). The measured isotope pat-
tern of the cyclic oligomers is in line with the calculated pattern on
the basis of natural abundance.
Further purification of the reaction product via flash chroma-
tography led to the isolation of the cyclic tetramer 2 in an 8.2%
overall yield. The larger cyclic oligomers could not be isolated from
the mixture. The ESI mass spectrum and the elemental analysis of
the isolated cyclic tetramer 2 confirmed the compound to be pure
and showed neither the presence of dimer 1 nor any of the larger
cyclic oligomers 3 and 4 (Fig. 2, top). The measured isotope pattern
of the cyclic tetramer 2 is in line with the calculated pattern. The
1H NMR spectrum in CDCl3 at 303 K showed a complicated set of
signals for such a simple compound. A temperature-dependent
Several conformations1,3 with different arrangements of the ben-
zene rings and R groups on the methine bridges with respect to one
another, and to the macrocycle plane are known for resorcin[4]are-
nes. These include crown, boat, chair, diamond and saddle. Unusual
resorcin[4]arene and pyrogall[4]arene conformations such as the
rarely observed rcct-diamond isomer of C1-resorcin[4]arene6a and
the C4t-pyrogall[4]arene (4t = tert-butyl) in the rcct-crown confor-
mation6b have been reported.
Careful tuning of the direct reaction between acetaldehyde and
2-nitroresorcinol under alkaline (NaOH/H2O) conditions, resulted
in the formation of a mixture of the dimer 1 and cyclic oligomers
2, 3 and 4 (Scheme 1). Using either Ca(OH)2 or K2CO3 instead of
NaOH resulted in similar mixtures containing the dimer and the
* Corresponding author. Tel.: +358 14 260 2672; fax: +358 14 260 2651.
E-mail address: kari.t.rissanen@jyu.fi (K. Rissanen).
Scheme 1. Synthesis and isolation of tetranitro-C1-resorcin[4]arene 2.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.10.075

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N. K. Beyeh, K. Rissanen / Tetrahedron Letters 50 (2009) 7369–7373
Figure 1. 1H NMR of the product mixture containing 1, 2, 3 and 4, signals of 2 are highlighted.
Figure 2. ESI-MS spectra of (top) tetranitro-C1-resorcin[4]arene 2 (inset: calculated and experimental isotope patterns of 2), and (bottom) the mixture of cyclic tetrameric 2,
pentameric 3 and hexameric 4 oligomers.
1H NMR measurement was then carried out to study the conforma-
tional dynamics of 2 and similarly a 1H1H COSY 2D NMR spectrum
was recorded to study the interactions between the protons. The
temperature-dependent 1H NMR shows that 2 possesses a stable
conformation between 223 and 323 K. At 253 K, for example
(Fig. 3), 4 equiv singlets were observed for the hydroxy groups be-
tween 11.0 and 11.3 ppm. There was slight overlapping of these
protons at 223 K. These peaks shifted up-field on increasing the
temperature with no overlapping. Two singlets were evident for
the aromatic hydrogens between 7.7 and 6.5 ppm which were rel-
atively constant at all temperatures. Three quartets for the CH pro-
tons were apparent between 4.6 and 5.3 ppm in a statistical 1:2:1
ratio. The smaller signals broadened at lower temperature and one
of them eventually overlapped with the larger signal at higher
temperatures. Similarly, three doublets in a statistical 1:2:1 ratio
were observed between 0.9 and 1.7 ppm for the CH3 protons. These

N. K. Beyeh, K. Rissanen / Tetrahedron Letters 50 (2009) 7369–7373
7371
Figure 3. 1H NMR of 2 at 253 K. Four singlets for the hydroxy groups, two singlets for the aromatic protons, three quartets for the CH protons in a statistical 1:2:1 ratio, and
similarly three doublets for the CH3 protons in a statistical 1:2:1 ratio.
Figure 4. 1H NMR temperature-dependent measurements on tetranitro-C1-resorcinarene 2 from 223 to 323 K.

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N. K. Beyeh, K. Rissanen / Tetrahedron Letters 50 (2009) 7369–7373
signals were relatively constant and a slight overlap of two of these
resonances at higher temperature was observed. The complete set
of 1H NMR spectra from 223 K to 323 K is shown in Figure 4. The
same phenomenon was apparent with the aromatic and aliphatic
protons in DMSO-d6, even at higher temperatures. The hydroxy
protons appeared as one broad peak in DMSO-d6. A similar pattern
was also observed in the 13C NMR spectrum in CDCl3.
asymmetric rcct-boat stereoisomer. By careful application and tun-
ing of the known procedures to reactions or conditions reported to
be unsuccessful can lead to the synthesis and isolation of interest-
ing novel compounds. Our results show that there are probably
many unprecedented resorcin[4]arene conformations to be discov-
ered and this could help in the design of novel molecular
architectures.
Fortunately, single crystals of tetranitro-C1-resorcin[4]arene 2
suitable for X-ray analysis were obtained via slow evaporation
from acetone. The X-ray structure confirmed an unprecedented
new stereoisomer for the resorcin[4]arene and pyrogall[4]arene
family which fully explains the rather strange 1H NMR spectra ob-
tained. The asymmetric nature of 2 is manifested by the low sym-
metry of the unit cell (triclinic) and the conformation can be
described as rcct-boat ( Fig. 5), being clearly different from the
rcct-diamond6a C1-resorcin[4]arene and the rcct-crown6b C4t-pyro-
gall[4]arene conformations. All the hydroxy hydrogens are hydro-
gen bonded to the nitro group oxygens, thus disrupting the normal
circular hydrogen bonding system observed in rccc resorcin[4]are-
nes.1,2,4,5 The 1H NMR spectrum is consistent with the syn–syn–
syn–anti configuration of the methyl groups. The two parallel nitro-
benzene rings are twisted towards each other, the contact
(O10AÁ Á ÁN23 distance) between the nitro groups is only 2.99 Å,
and is slightly shorter than the sum of the van der Waals radii of
the O and N atoms (3.07 Å). The angles between the nitrobenzene
rings and the plane defined by the four methane carbons, 73.3° and
83.3° and À24.7° and À4.2°, deviate significantly from the regular
boat conformation where the angles are 90° and 0°. The probable
cause of this distortion is the steric repulsion caused by the anti-
methyl group [C(29)].
To a solution of 2-nitroresorcinol (5.0 g, 0.0322 mol) in H2O
(100 ml) and NaOH (2.6 g, 0.0645 mol) at 0 °C, acetaldehyde
(1.42 g, 0.0322 mol) was added in one portion. The mixture was
maintained at 0 °C for 2 h with stirring under an N2 atmosphere.
After stirring for 24 h at 60 °C, the dark-coloured mixture was
cooled to 0 °C before being neutralized with HCl (0.2 mol). A red
precipitate was separated from the aqueous medium and was fil-
tered, washed with H2O to eliminate HCl and NaCl and dried. The
reddish solid obtained was recrystallized from MeOH (ꢁ50 ml).
The recrystallized product was further purified via column chro-
matography (eluent: CH2Cl2/MeOH, 95:5) to give 4.08 g of a mix-
ture of the dimer 1, and tetramer 2, pentamer 3 and hexamer 4.
This mixture was subjected to further purification via flash chro-
matography (eluent: CH2Cl2/hexane, 40–20% gradient) which re-
sulted in a partial extraction of tetramer 2 (0.48 g, to give an
overall 8.2% yield) as a reddish powder. Mp >300 °C, (found C,
43.06; H, 3.52; N, 5.83; C32H28N4O16Á1.5CHCl3Á1.5H2O requires C,
43.23; H, 3.52; N, 6.02). [C32H28N4O16 requires 724.604; ESI-TOF
MS [MÀH]À found 723.02]. 1H NMR (500 MHz, CDCl3, 50 °C) d:
11.10, 11.03, 11.00, 10.97 (s, 8H, Ar–OH), 7.53, 6.75 (s, 4H, Ar–H),
5.23, 4.78 (q, 4H, J 7.2 Hz, CH), 1.59, 1.55, 1.16 (d, 12H, J 7.3 Hz,
CH3); 13C NMR (126 MHz, CDCl3, 30 °C,) d:152.1, 152.0, 151.8,
151.6 (Ar–C–OH) 135.0, 134.6 (Ar–C–H) 124.8, 124.5, 124.0,
123.8, 123.7, 123.3 (Ar–C–C/Ar–C–N), 31.3, 29.7, 27.3 (C–H) 20.5,
20.2, 19.1 (C–H3).
In conclusion, we have presented here the first example of a di-
rect synthesis of a tetranitro-Calkyl-resorcin[4]arene from 2-nitr-
oresorcinol and acetaldehyde under alkaline conditions. The 1H
NMR studies and X-ray structure of the tetranitro-C1-resor-
cin[4]arene 2 confirm a unique, thermally stable and completely
Suitable single crystals for X-ray analysis were obtained by slow
evaporation of tetranitro-C1-resorcinarene 2 from acetone. Crystal
data C32H28N4O16Á2C3H6O, red prisms 0.3 Â 0.2 Â 0.1 mm, Bruker–
Nonius Kappa APEXII diffractometer, Mr = 840.74, Dcalcd = 1.448 Mg/
m3, triclinic, P1, Z = 2, MoK radiation [k = 0.71073 Å], a =
ꢀ
a
12.9107(3), b = 13.2590(3), c = 13.5419(4) Å,
70.667(2),
= 63.052(2)°Å, V = 1928.55(8) Å3,
T = 173.0(1) K, 21,883 measured reflections, 6716 independent,
4650 reflections with I > 2
(I), hmax = 25°, refinement on F2, 571
a
= 74.086(2), b =
c
l
= 0.12 mmÀ1
,
r
parameters, Rint = 0.042, R = 0.064 [F2 > 2 (F2)], wR(F2) = 0.178,
r
S = 1.02,
Dq
max = 0.78 e ÅÀ3 and
Dq
min = À0.39 e ÅÀ3
.
Crystallographic data (excluding structure factors) for the struc-
tures in this Letter have been deposited with the Cambridge Crys-
tallographic Data Centre as supplementary publication no. 725579.
Copies of the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax: +44-(0)1223-
336033 or e-mail: deposit@ccdc.cam.ac.uk).
Acknowledgements
We gratefully acknowledge the Academy of Finland (Proj. No.
212588) and the University of Jyväskylä for financial support.
Dipl.-chem. Dominik Weimann, Freie Universität Berlin, Germany,
is thanked for the HPLC separation experiments.
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