Synthesis and Crystal Structure of a Novel Glycoluril Molecular Scaffold

Article abstract of DOI:10.1007/s10870-016-0646-y

Abstract: A novel glycoluril scaffold 1, namely 1,6-(1,2-xylylene)-3,4-(1,3-dimetheneyl-hexahydropyrimidine)tetrahydroimidazo[4,5-d]imidazole-2,5(1H,3H)-dione, was synthesized by the Mannich reaction of 1,6-(1,2-xylylene)tetrahydroimidazo[4,5-d]imidazole-2,5(1H,3H)-dione 5 with propanediamine and paraformaldehyde. The yielded product 1 was confirmed with IR, NMR, EI-MS. X-ray crystallographic technique was also conducted and the result showed the crystal belongs to monoclinic system, space group P2₁/c with unit cell parameters a?=?10.6892(11)??, b?=?12.1226(9)??, c?=?13.7822(13)??, α?=?90°, β?=?112.620(4)°,γ?=?90°, V?=?1648.5(3)??³, Z?=?4, D_c?=?1.428, M_r?=?354.41, μ?=?0.098?mm^?1, F(000)?=?752, R₁?=?0.0522 and wR₂?=?0.1138. Graphical Abstract: A novel molecular scaffold, containing a heterocyclic ring instead of an aromatic ring, was synthesized by the Mannich reaction based on glycoluril.[Figure not available: see fulltext.]

Full text of DOI:10.1007/s10870-016-0646-y

J Chem Crystallogr
DOI 10.1007/s10870-016-0646-y
BRIEF COMMUNICATION
Synthesis and Crystal Structure of a Novel Glycoluril Molecular
Scaffold
Zhi-guo Wang1 Wei Yu1 He-qi Zheng1 Zhi-gang Wang1
•
•
•
Received: 7 October 2015 / Accepted: 24 March 2016
Ó Springer Science+Business Media New York 2016
Abstract A novel glycoluril scaffold 1, namely 1,6-(1,2-
xylylene)-3,4-(1,3-dimetheneyl-hexahydropyrimidine)te-
trahydroimidazo[4,5-d]imidazole-2,5(1H,3H)-dione, was
synthesized by the Mannich reaction of 1,6-(1,2-xy-
lylene)tetrahydroimidazo[4,5-d]imidazole-2,5(1H,3H)-dione
5 with propanediamine and paraformaldehyde. The yielded
product 1 was confirmed with IR, NMR, EI-MS. X-ray
crystallographic technique was also conducted and the result
showed the crystal belongs to monoclinic system, space
˚
group P21/c with unit cell parameters a = 10.6892(11) A,
˚
˚
b = 12.1226(9) A, c = 13.7822(13) A, a = 90°, b =
3
˚
112.620(4)°,c = 90°, V = 1648.5(3) A , Z = 4, Dc =
, F(000) = 752,
1.428, Mr = 354.41, l = 0.098 mm-1
R1 = 0.0522 and wR2 = 0.1138.
Graphical Abstract A novel molecular scaffold, con-
taining a heterocyclic ring instead of an aromatic ring, was
synthesized by the Mannich reaction based on glycoluril.
Keywords Synthesis Á Crystal structure Á Glycoluril
Introduction
Glycoluril and its derivatives, due to their precaved structure
and special bonding vector information, are widely used as
an important building blocks for supramolecular chemistry,
for example, molecular scaffold [1], molecular clips [2–4]
and molecular baskets [5], molecular bowls [6], molecular
capsules [7–9], and the cucurbit[n]uril family of macrocy-
cles [10–14]. Among these versatile structures, glycoluril-
derived clips and scaffolds attracted much interest due to
their fuctions acting as excellent receptors [15–18]. As our
purpose to obtain some new artificial receptors, a novel
glycouril molecular scaffold, modified from molecular clip
using a heterocyclic ring instead of an aromatic ring, was
synthesized and its structure were reported here.
& Zhi-guo Wang
chwangzg@aliyun.com
1
Hubei Key Laboratory of Mine Environmental Pollution
Control & Remediation, School of Chemistry and Chemical
Engineering, HuBei Polytechnic University,
Huangshi 435003, Hubei, People’s Republic of China
123

J Chem Crystallogr
X-ray Crystal Structure Determination
Experimental
The colorless single crystal was cultured from a solution of
methanol by slow evaporation at room temperature.
A single crystal of approximate dimensions 0.40 mm 9
0.31 mm 9 0.30 mm was used. X-ray diffraction data
were collected at 173(2) K on a Bruker Smart-1000CCD
diffractometer, using graphite monochromatized Mo
The melting point was determined with XT4A
micromelting point apparatus. Infrared spectra was recor-
ded as KBr pollets on a PE-983 spectrometer. The 1H NMR
and 13C NMR were measured on a Bruker Avance 300
spectrometer with TMS as internal reference and DMSO-
D6 as solvent. MS was obtained with Finnigan Trace MS
instrument using EI method.
˚
Karadiation (k = 0.71073 A). A total of 3739 independent
reflections were collected in the range of 3.071° \ h \
27.489° by x scan mode. The crystal data, data collection,
and refinement parameters for 1 were presented in Table 1.
The structure was solved by direct methods using the
program SHELXS-97 [22]. Refinements were done by the
full-matrix least-squares on F2 using SHELXL-97. Non-
hydrogen atoms were refined with anisotropic displacement
parameters. Figure 1 was drawn by using the program
OLEX2 [23], Figs. 2 and 3 were drawn by using the pro-
gram Mercury [24].
Synthesis of the Title Compound
The title compound was prepared according to Scheme 1.
Compounds 2 [19], 3 [20], 4, 5 [21] were synthesized
according to the literature method.
Preparation of 1
A suspension of 0.49 g of compound 5 (2.0 mmol) in
0.5 mL of 37 % aqueous formaldehyde (6.2 mmol) and
30 mL of methanol in a 100-mL flask was brought to reflux
in an oil bath with magnetic stirring. To this mixture was
added slowly a solution of 0.14 g of propanediamine
(2.0 mmol) in 20 mL of methanol dropwise, and refluxing
was then continued overnight. The reaction mixture was
cooled to room temperature, and unreacted compound 5
(0.10 g) was removed by filtration. After rotary evapora-
tion the residue was chromatographed (SiO2, methanol/
ethyl acetate 1:2) to yield 1 (0.29 g, 42 %) as a white solid.
M.p. 240–242 °C. IR (KBr, cm-1): 3025w, 2912 m,
Results and Discussion
Selected bond distances and bond angles are listed in
Table 2. Selected torsion angle are given in Table 3. An
OLEX2 view of the molecule with the atomic numbering
(thermal ellipsoids drawn at 50 % probability) is shown in
Fig. 1.
The bond distances and bond angles of the title com-
pound are in good agreement with the corresponding val-
ues obtained in case of related glycoluril derivatives [25–
27]. Two imidazole rings which belong to the gly-
colurilskeleton both have certain torsion and are nonplanar.
The distance between the two carbonyl oxygens
1
1709 s, 1650 s, 1608 s, 1456 s, 1120 s, 740 s. H NMR
(300 MHz, DMSO-D6): d7.30–7.20(m, 4H), 5.64(d,
J = 8.0 Hz, 1H), 5.32(d, J = 7.9 Hz, 1H), 4.60–4.52(m,
6H), 4.10–4.00(m, 3H), 3.81(d, J = 11.4 Hz, 1H), 2.70–
2.49(m, 4H). 13C NMR (75 MHz, CDCl3):d156.8, 137.9,
129.2, 127.6, 76.6, 69.4, 68.0, 64.0, 46.7, 45.1. EI-MS: m/z
355 (100, [M?1]?).
˚
C(12)=O(1)ÁÁÁO(2)=C(8) is 5.848(2) A. The six-member
heterocyclic ring (N5–C10–N6–C16–C17–C18) adopts a
stable chair conformation. The dihedral angle between the
plane A (N5–N6–C17) and plane B (C10–C16–C18) is
0.68°. The angle between the benzene ring plane and the
.
KCNO
Br2
(1) NaN3
(2) PPh3
(3) HCl
NH2 HCl
NHCONH2
NHCONH2
Br
Br
.
NH2 HCl
H2O
3
4
2
O
O
H2N
NH2
N
N
NH
NH
N
N
N
N
glyoxal
HCl
N
N
paraformaldehyde
O
1
O
5
Scheme 1 Preparation of the title compound
123

J Chem Crystallogr
Table 1 Crystal data, summary
of data collection and structure
refinement
CCDC No.
1426236
18H22N6O2
Empirical formula
Formula weight
Crystal system
Space group
C
354.41
Monoclinic
P21/c
˚
a = 10.6892(1) A
Cell dimensions
˚
b = 12.1226(9) A
˚
c = 13.7822(1) A
b = 112.620(4)°
1648.5(3)
3
˚
Volume (A )
Z
4
Density (calculated) (Mg/m3)
Absorption coefficient (mm-1
F000
1.428
)
0.098
752
Index ranges
-13 B h B 13
-15 B k B 15
-17 B l B 17
11,421
Reflections collected
Independent reflections
Absorption correction
3739 (Rint = 0.0264)
Semi-empirical from equivalents
1.0000 and 0.8889
Full-matrix least-squares on F2
3739/0/235
Max. and min. transmission coefficients
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
1.163
Final R indices [I [ 2r(I)]
R indices (all data)
R1 = 0.0484, wR2 = 0.1117
R1 = 0.0522, wR2 = 0.1138
n/a
Extinction coefficient
Largest diff. peak and hole, e (A-3
)
0.249 and -0.219
Fig. 2 The dimeric aggregates via C—H…p hydrogen bond. Sym-
metry code: 1 - x, 1 - y, 1 - z
Fig. 1 Molecular structure of the title compound
cavity, which may be suitable for binding some small guest
by hydrogen bond.
plane A (C16–C17–C18), plane B (C16–C18–N5–N6) is
54.70° and 10.83° respectively. The distance between the
benzene ring centroid and six-member heterocyclic ring
Viewed from Fig. 2, dimeric aggregates are formed
through C18—H18BÁÁÁp hydrogen bond. The distance
˚
centroid is 6.078 A. The glycoluril scaffold has a rigid
123

J Chem Crystallogr
Fig. 3 The packing
arrangement viewed down the
b-axis. Hydrogen bonds are
shown by dashed lines
˚
between the hydrogen atom 18B and the centroid of the
˚
aromatic ring is 3.506 A, and the bond angle of the C18—
Table 2 Selected bond lengths (A) and angles (°) for non-hydrogen
atoms
H18BÁÁÁp hydrogen bond is 140.72°. p–p stacking inter-
actions is not found in the crystal structure.
O1–C12
1.2207(18)
1.2248(18)
1.3714(18)
1.4589(18)
1.4469(18)
1.3634(19)
1.387(2)
C10–N5–C18
C11–N5–C10
C11–N5–C18
C9–N6–C10
C9–N6–C16
C10–N6–C16
C2–C1–C6
111.16(13)
117.50(13)
116.13(13)
118.51(12)
116.21(12)
100.49(13)
119.61(13)
119.55(13)
125.79(14)
126.03(14)
108.14(12)
113.31(11)
O2–C8
The packing arrangement viewed down the b-axis is
show in Fig. 3. The title compound assembles to a two-
dimensional chain structure by intermolecular hydrogen
N1–C12
N1–C13
N1–C14
˚
bond C14—H14ÁÁÁO2 [2.594(3) A, 143.4°] with symmetry
N2–C8
code -x, 1 - y, -z.
C1–C2
In conclusion, a novel glycoluril molecular scaffold was
synthesized by the Mannich reaction of 5 with propanedi-
amine and paraformaldehyde. The glycoluril scaffold has a
rigid cavity, may be suitable for binding some small guest
by hydrogen bond. Futher studies on its molecular recog-
nition are in progress.
C14–C15
C14–N1–C13
C8–N2–C7
C8–N2–C7
C14–N2–C7
1.5501(19)
122.08(11)
122.56(12)
112.82(11)
122.56(12)
C2–C1–C13
O1–C12–N1
O1–C12–N4
N1–C12–N4
N1–C13–C1
Table 3 Selected torsion
angles (°) for non-hydrogen
atoms
N1–C14–C15–N3
N2–C14–C15–N3
N2–C14–C15–N4
N6–C16–C17–C18
C1–C6–C7–N2
C4–C5–C6–C7
122.17(11)
2.30(13)
C11–N4–C12–N1
C11–N4–C15–C14
C11–N5–C10–N6
C11–N5–C18–C17
C12–N1–C13–C1
C12–N4–C15–N3
C12–N4–C15–C14
C13–N1–C12–O1
C15–N3–C8–N2
C15–N3–C9–N6
C15–N4–C11–N5
C16–C17–C18–N5
170.17(12)
-172.60(13)
-85.15(17)
88.89(17)
-81.65(17)
-111.45(13)
0.38(15)
-117.61(11)
-49.98(18)
62.88(18)
-179.81(13)
-116.77(15)
-167.10(12)
52.33(17)
C5–C6–C7–N2
C7–N2–C8–N3
C7–N2–C14–N1
C7–N2–C14–C15
C8–N2–C7–C6
C8–N3–C15–C14
-17.8(2)
4.76(15)
164.38(12)
86.31(17)
81.13(18)
-83.91(18)
48.70(18)
-4.36(14)
123

J Chem Crystallogr
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