A facile one-pot synthesis and the crystal structure of a molecular clip derived from diphenylglycoluril

Article abstract of DOI:10.1007/s00706-007-0850-8

A facile procedure for the one-pot synthesis of a clip molecule via condensation of diphenylglycoluril, paraformaldehyde, and 4-dimethoxybenzene in the presence of methanesulfonic acid is described. The advantages of this method are mild conditions, single product formation and good yield. Especially, the procedure of the product purification is more simple and convenient. In addition, the clip molecule is characterized by X-ray crystal structure analysis, which shows different weak interactions forces compared to the structure reported previously.

Full text of DOI:10.1007/s00706-007-0850-8

Monatsh Chem 139, 949–952 (2008)
DOI 10.1007/s00706-007-0850-8
Printed in The Netherlands
A facile one-pot synthesis and the crystal structure of a molecular clip
derived from diphenylglycoluril
1
;2
1
2
Zhi-Guo Wang , Zi-Hua Wang , Lei Teng
1
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education,
Chemistry Department of Central China Normal University, Wuhan, China
2
School of Chemical and Materials Engineering, Huangshi Institute of Technology, Huangshi, China
Received 14 August 2007; Accepted 8 November 2007; Published online 26 June 2008
Springer-Verlag 2008
#
Abstract A facile procedure for the one-pot synthesis
of a clip molecule via condensation of diphenylgly-
coluril, paraformaldehyde, and 4-dimethoxybenzene
in the presence of methanesulfonic acid is described.
The advantages of this method are mild conditions,
single product formation and good yield. Especially,
the procedure of the product purification is more sim-
ple and convenient. In addition, the clip molecule
is characterized by X-ray crystal structure analysis,
which shows different weak interactions forces com-
pared to the structure reported previously.
gen bond, ꢀ–ꢀ stacking interactions, and a so-called
‘‘cavity effect’’ [2–5]. In addition, in the solid state,
the molecule can form head-to-head dimeric struc-
tures, in which the cavity of one molecule is filled by
one of the side-walls of its dimeric partner and vice-
versa [6–9]. This property was applied to create
well-defined nanosized materials [10–12]. Herein,
we report a facile procedure for the synthesis of this
molecule and different interactions forces in its crys-
tal structure.
Keywords One-pot synthesis; Crystal structure; Molecular
clip; Diphenylglycoluril.
Results and discussion
In our research, we need 4 as an intermediate to
synthesize other functional receptors. There are two
synthesis routes used to synthesize the compound.
Route I (Scheme 1, 1 ! 2 ! 4): diphenylglycoluril
Introduction
In 1987, Nolte et al. synthesized some organic recep-
tors based on diphenylglycoluril commonly referred
to as ‘‘molecular clips’’ [1], such as 4. This molecule
possesses a well-defined and rigid U-shaped cavity,
which is formed by the glycoluril framework and
two aromatic side walls. With its preorganized cleft,
it is a good receptor for a 1,3-dihydroxybenzene guest
molecule in a chloroform solution through hydro-
1
[13] was treated with paraformaldehyde and NaOH
in DMSO to yield tetrakis(hydroxymethyl) derivative
(85%) [14], the latter compound was reacted with
2
an excess of 1,4-dimethyoxybenzene in 1,2-di-
chloroethane using 4-methylbenzenesulfonic acid
as catalyst and gave 4 in 50% yields [1]. Route II
(
Scheme 1, 1 ! 3 ! 4): as preparation of 2, the re-
action mixture was adjusted to pH 1 with con-
centrated HCl, 1 was transformed to intermediate
cycloether 3 (40%) [13], which reacted with an
Correspondence: Zhi-Guo Wang, Key Laboratory of Pesticide
and Chemical Biology, Ministry of Education, Chemistry
Department of Central China Normal University, Wuhan
excess of 1,4-dimethoxybenzene in H SO or a
2
4
4
30079, China. E-mail: chwangzg@hsit.edu.cn
mixture of acetic anhydride and trifluoroacetic acid

9
50
Z.-G. Wang et al.
formation, and good yield. Especially, the proce-
dure of the product purification is more simple and
convenient.
In addition, we describe here the solid structure of
a new polymorph of 4 and compare it with Nolte’s
structure. The colorless single crystal of 4 was cul-
tured from a solution of chloroform by slow evap-
oration at room temperature. The X-ray crystal
structure of 4 is shown in Fig. 1 with 30% thermal
ellipsoids probability. The molecule possesses a C2
symmetry axis. The bond distances and bond angles
of the title compound are in good agreement with the
corresponding values obtained in case of related gly-
coluril derivatives [3]. The angle between the mean
Scheme 1
planes defined by the fused 2-imidazolidone rings is
ꢀ
to furnish 4 in 94, 96% yields [14]. As two steps
involved acidic conditions, we hoped to identify
an appropriate acid which would allow to per-
form the whole procedure as a one-pot synthesis
70.2 and the distance between the two carbonyl oxy-
gens amounts to 5.51A. The dihedral angle between
˚
ꢀ
the aromatic ring sides is 40.1 with the centers of the
˚
benzene rings 6.68 A apart.
(Scheme 1). In our study, several acid systems (H SO ,
HCl, CF COOH, CF SO H, CH SO H, and 4-
2 4
In the structure obtained by Nolte, the molecules
are arranged as consecutive head-to-head dimers
3
3
3
3
3
methylbenzenesulfonic acid) were tested and metha-
nesulfonic acid was proven to be most effective for
the reaction. In the presence of methanesulfonic ac-
id, we can obtain 4 in good yield (71%) (see experi-
ment section). In contrast to the previously reported
procedures our method does not require the purifi-
cation of intermediates. Moreover, the advantages
of this method are mild conditions, single product
(
Fig. 2a). Sheets of clips giving an interwoven net-
work (Fig. 2b) which is stabilized by ꢀ–ꢀ stacking
interactions between the clip layers [7].
Interestingly, we cannot find head-to-head dimers in
the crystal structure. In Fig. 3a, there are no direction-
specific interactions between the clipped molecules.
Instead, tail-to-tail dimers are formed, which are
linked by intermolecular hydrogen bond (Fig. 3b).
The intermolecular hydrogen bonds between atoms
are as follows: C(16)–H(16)ꢁ ꢁ ꢁO(3) has length
C1a
˚
ꢀ
.332(5) A and an angle of 157.4 , with symmetry
3
C2 C4 C5
C4a
C5a
code ꢂx, 1 ꢂ y, ꢂz.
0
1a
C1
In addition, ꢀ–ꢀ stacking interactions are also not
observed between the clip layers. These layers are
linked into an interwoven network by weak inter-
0
2
C3a
C2a
02a
C6 C301
C8
C8a
C6a
C7a
C7
03a
0
3
C9a
C10a
C10
C9
C19a
N1a
N2a
N1
C19
N2
C11a
C11
C13
C12
C12a
C13a
C17a
C14
C17
C16a
C15a
C14a
C16
C15
Fig. 1 The molecular structure of 4
Fig. 2 Part of the crystal structure of Nolte’s

A facile one-pot synthesis and the crystal structure of a molecular clip derived from diphenylglycoluril
951
Fig. 3 Part of the crystal structure of 4
5
7
,9,14,18-Tetrahydro-1,4,10,13-tetramethoxy-19,20-diphenyl-
H,16H-6,17:8,15-dimethanodibenzo[e,l][1,3,8,10]tetra-
azacyclotetradecine-7,16-dione (4)
A mixture of 2.94 g (diphenylglycoluril 10.0mmol), 1.5 g
3
(paraformaldehyde 50.0 mmol), and 1.3 cm (methanesulfonic
acid 20.0mmol) in 35cm 1,2-dichloroethane was heated at
reflux for 3 h under a Soxhlet apparatus filled with molecular
3
˚
sieves (4A). After cooling, 2.76 g (1,4-dimethoxybenzene
2
0.0mmol) was added and reflux was continued for 20 h. The
ꢀ
reaction mixture was stored overnight at ꢂ6 C, then the pre-
3
cipitate was filtered off, washed with 2ꢃ20cm EtOAc, and
dried in vacuo. Compound 4 (4.38 g, 71%) was obtained as a
ꢀ
1
white solid. Mp >300 C; H NMR (400MHz, CDCl3):
ꢁ
1
3
¼ 7.08 (s, 10H, ArH), 6.48 (s, 4H, ArH), 5.60 (d, J ¼
6.0Hz, 4H, NCH Ar), 3.76 (d, J ¼ 16.0Hz, 4H, NCH Ar),
2
2
þ
.72 (s, 12H, OMe); EI-MS: m=z ¼ 619 (26, [Mþ 1] ), 151
(100).
X-Ray crystallography
A single crystal of approximate dimensions 0.30 mmꢃ
0
collected at 292(2) K on a Bruker Smart-1000CCD dif-
.20mmꢃ0.20 mm was used. X-Ray diffraction data were
Fig. 4 Packing diagram of 4 viewed along the y-axis
fractometer, using graphite monochromatized Mo Kꢂ radia-
˚
tion (l ¼ 0.71073 A). The crystal belongs to monoclinic, space
group C2=c with a ¼ 19.677(2), b ¼ 12.2903(15), c ¼
3
molecular C–Hꢁ ꢁ ꢁꢀ interactions (Fig. 4). This inter-
˚
˚
1
D
3.9591(17)A, ꢃ ¼ 116.232(2), V ¼ 3028.1(6) A , Z ¼ 4,
3
ꢂ1
action, with the proton shared between C(1) and the
-electron system of the benzene ring C(12)–C(17), has
c
¼ 1.357 g=cm , ꢄ(MoK
ꢂ
) ¼ 0.094 mm , F(000)¼ 1304.
A total of 3126 reflections were collected in the range of
2
ꢀ
ꢀ
˚
ꢀ
.02<ꢅ<27.00 at room temperature, and 8778 were inde-
an Hꢁꢁ ꢁꢀ distance of 3.04 A and an angle of 167.8 ,
with symmetry code ꢂ1=2 þ x, 3=2 ꢂ y, ꢂ1=2 þ z.
pendent (Rint ¼ 0.0291), of which 3291 observed reflections
with I>2ꢆ(I) were used in the structure determination and
refinements. The structure was solved by direct methods using
the program SHELXS-97 [15]. Refinements were done by
2
Experimental
the full-matrix least-squares on F using SHELXL-97 [16].
Nonhydrogen atoms were refined with anisotropic displace-
ment parameters. All hydrogen atoms were located from a
difference Fourier map and refined without restrains. A full-
matrix least-squares refinement gave the final R ¼ 0.0529,
wR ¼ 0.1277. CCDC-626012 contains the supplementary
crystallographic data for this paper. These data can be obtained
free of charge at www.ccdc.cam.ac.uk=conts=retrieving.html
General
The melting point was determined with XT4A micromelting
1
point apparatus. The H NMR was recorded on a Mercury
Plus-400 spectrometer with TMS as internal reference and
CDCl as solvent. MS were obtained with Finnigan Trace
MS instrument using EI method.
3

9
52
Z.-G. Wang et al.
or from the Cambridge Crystallographic Data Centre (CCDC),
1
5. Reek JNH, Priem AH, Engelkamp H, Rowan AE,
Elemans JAWW, Nolte RJM (1997) J Am Chem Soc
119:9956
2 Union Road, Cambridge CB2 1EZ, UK; Fax: þ44(0)1223-
3
36033; e-mail: deposit@ccdc.cam.ac.uk.
6
. Holder SJ, Elemans JAWW, Barber a´ J, Rowan AE, Nolte
RJM (2000) Chem Commun:355
Acknowledgements
7. Holder SJ, Elemans JAWW, Donners JJJM, Boerakker
MJ, de Gelde R, Barber a´ J, Rowan AE, Nolte RJM (2001)
J Org Chem 66:391
The authors are grateful to Prof. An-Xin Wu for helpful dis-
cussions. This study was financially supported by National
Natural Science Foundation (No. 20672042), Innovative
Team and Key Project (No. Z2006zd02) of Huangshi
Institute of Technology.
8
. Elemans JAWW, Boerakker MJ, Holder SJ, Rowan AE,
Cho WD, Percec V, Nolte RJM (2002) Proc Natl Acad Sci
USA 99:5093
9
. Reek JNH, Elemans JAAW, de Gelder R, Beurskens
PT, Rowan AE, Nolte RJM (2003) Tetrahedron 59:
1
75
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