Syntheses and crystal structures of three electron poor N-vinyltheophylline derivatives

Article abstract of DOI:10.1007/s10870-011-0107-6

Protonation of the highly reactive 1:1 intermediates, produced in the reaction between triphenylphosphine and alkyl acetylenecarboxylates (or dialkyl acetylenedicarboxylates) by theophylline leads to vinyltriphenylphosphonium salts, which undergo Michael addition reaction with conjugate base to produce phosphorus ylides. Silica gel was found to catalyze conversion of the phosphorus ylides to electron-poor N-vinyl imidazoles in solvent-free conditions under thermal (90 °C, 1 h) conditions. The structures of these compounds were confirmed by IR, ¹H, and ¹³C NMR spectroscopy, and single crystal X-ray structure determination. The structural analysis of the products indicated that the reaction is completely regio- and stereoselective. Springer Science+Business Media, LLC 2011.

Full text of DOI:10.1007/s10870-011-0107-6

J Chem Crystallogr (2011) 41:1376–1385
DOI 10.1007/s10870-011-0107-6
ORIGINAL PAPER
Syntheses and Crystal Structures of Three Electron Poor
N-Vinyltheophylline Derivatives
•
Ali Ramazani Azam Farshadi Amir Mahyari
•
•
´
Katarzyna Slepokura Tadeusz Lis
•
•
Morteza Rouhani
Received: 3 February 2011 / Accepted: 15 April 2011 / Published online: 27 April 2011
ꢀ Springer Science+Business Media, LLC 2011
Abstract Protonation of the highly reactive 1:1 interme-
diates, produced in the reaction between triphenylphosphine
and alkyl acetylenecarboxylates (or dialkyl acetylenedi-
carboxylates) by theophylline leads to vinyltriphenylpho-
sphonium salts, which undergo Michael addition reaction
with conjugate base to produce phosphorus ylides. Silica gel
was found to catalyze conversion of the phosphorus ylides to
electron-poor N-vinyl imidazoles in solvent-free conditions
under thermal (90 ꢁC, 1 h) conditions. The structures of
these compounds were confirmed by IR, 1H, and 13C NMR
spectroscopy, and single crystal X-ray structure determina-
tion. The structural analysis of the products indicated that the
reaction is completely regio- and stereoselective.
N-ligands coordinating transition metals [1, 2]. The appli-
cation of imidazoles in medicinal chemistry [3] or
chemistry of natural products/alkaloids [4, 5] or of 1,
3-disubstituted imidazole salts as ionic liquids [6, 7] are
also well known.
1-Vinylimidazole is employed as a copolymer in the
production of cationic polymers for various uses. Alkyl-
imidazoles are used as hardeners for epoxy resins and for
polyurethanes [8]. Less important uses for alkyl- and ary-
limidazoles include photography and dyes.
b-Additions of nucleophiles to the vinyl group of vinylic
phosphonium salts leading to the formation of new alky-
lidenephosphoranes has attracted much attention as a very
convenient and synthetically useful method in organic
synthesis [9]. Organophosphorus compounds have been
extensively used in organic synthesis as useful reagents as
well as ligands of a number of transition metal catalysts
[10]. Phosphorus ylides are a class of special type of
zwitterions, which bear strongly nucleophilic electron rich
carbanions. The electron distribution around the P?–C-
bond and its consequent chemical implications had been
probed and assessed through theoretical, spectroscopic and
crystallographic investigations [9]. The nucleophilicity at
the ylidic carbon is a factor of essential mechanistic
importance in the use of these ylides as Wittig reagents.
Phosphorus ylides are important reagents in synthetic
organic chemistry, especially in the synthesis of naturally
occurring products, compounds with biological and phar-
macological activity [11]. These ylides are usually pre-
pared by treatment of a phosphonium salt with a base, and
phosphonium salts are usually obtained from a phosphine
and an alkyl halide. Phosphonium salts are also prepared by
Michael addition of phosphorus nucleophiles to activated
olefins and in other ways [12]. The phosphonium salts are
most often converted to the ylide by treatment with a strong
Keywords Silica gel ꢀ Theophylline ꢀ Acetylenic esters ꢀ
Vinyltriphenylphosphonium salts ꢀ Crystal structure ꢀ
N-Vinyl imidazole
Introduction
Imidazole chemistry currently attracts considerable atten-
tion, where the imidazole derivatives are widely applied as
A. Ramazani (&) ꢀ A. Farshadi ꢀ A. Mahyari
Chemistry Department, Zanjan University, PO Box 45195-313,
Zanjan, Iran
e-mail: aliramazani@gmail.com
´
K. Slepokura ꢀ T. Lis
Faculty of Chemistry, University of Wrocław, 14 Joliot-Curie
Street, 50-383 Wrocław, Poland
M. Rouhani
Young Researchers Club, Zanjan Branch, Islamic Azad
University, Zanjan, Iran
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J Chem Crystallogr (2011) 41:1376–1385
1377
base, though weaker bases can be used if the salt is acidic
enough. In recent years, we have established a one-pot
method for the synthesis of stabilized phosphorus ylides
[13–22]. In this paper, we wish to describe the preparation
of sterically congested electron-poor N-vinyl imidazoles
from alkyl acetylenecarboxylates (or dialkyl acetylenedi-
carboxylates) and theophylline in the presence of triphen-
ylphosphine in fairly good yields.
intermediates 7 in CH2Cl2. Silica gel powder was found to
catalyze conversion of the zwitterionic intermediates 7 to
electron-poor imidazoles 8 in solvent-free conditions [24]
under thermal (90 ꢁC, 1 h) conditions. In the absence of the
SiO2 powder, the conversion of the zwitterionic intermediate
7 to electron-poor N-vinyl imidazoles 8(a–b) was not
observed and decomposition of the starting materials was
observed (Scheme 1). The reaction proceeds smoothly and
cleanly under mild conditions and no side reactions were
observed. The mechanism of the reaction has not been
established experimentally. However, a possible explana-
tion [24] is proposed in Scheme 1.
Results and Discussion
The zwitterionic intermediate 7 may result from initial
addition of triphenylphosphine 1 to the alkyl acetylene-
carboxylate 2 and concomitant protonation of the 1:1 adduct
3, followed by attack of the NH-acid anion on the vinyl-
triphenylphosphonium cation to form the phosphorane 6
(Scheme 1). That phosphorane 6 undergoes intramolecular
proton transfer [23] leading to formation of zwitterionic
intermediate 7. TLC indicated formation of zwitterionic
We have also used dialkyl acetylenedicarboxylate and
ethyl 3-phenyl-2-propynoate 11 (Scheme 2) instead of
alkyl acetylenecarboxylate 2 in this reaction. The com-
pound 14 may result from initial addition of triphenyl-
phosphine to the dialkyl acetylenedicarboxylate or ethyl
3-phenyl-2-propynoate and concomitant protonation of the
1:1 adduct 12, followed by attack of the NH-acid anion
[24] on the vinyltriphenylphosphonium cation to form the
Scheme 1 Proposed
CH3
mechanism for the formation of
electron-poor N-vinyl
imidazoles 8(a–b)
N
O
O
N
N
N
H
CH3
O
H
C
OR
4
CH2Cl2
-10 0C
C
:PPh3
1
+
H
C
C
C
OR
PPh3
O
2
3
H
CH3
N
SiO2
90 0C
1 h
H
C
N
H
Ph3P
O
C
CH3
N
N
N
N
C
CH
OR
N
O
H-shift
Ph3P
OR
O
O
O
N
O
CH3
CH3
6
5
H
C
N
N
H
O
H
CH3
O
N
CH
C
N
CH3
N
N
Ph3P
:PPh3
+
OR
O
O
OR
N
N
O
O
CH3
CH3
8 (a,b)
7
8a: R=Me ; 8b: R=Et
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J Chem Crystallogr (2011) 41:1376–1385
Scheme 2 Synthesis of
electron-poor
N-vinyltheophyllines 16(a–b)
CH3
N
O
N
N
N
H
CH3
E1
C
4
CH2Cl2
-10 0C
O
C
E2
:PPh3 + E1
C
C
E2
PPh3
1
11
12
E1
CH3
N
SiO2
H
N
90 0
1 h
C
E1
CH3
Ph3P
C
N
N
N
N
C
C
CH
N
O
H-shift
Ph3P
E2
E2
O
N
O
CH3
O
CH3
14
13
E1
C
N
N
H
E1
CH
CH3
O
N
C
N
CH3
N
N
E2
Ph3P
E2
:PPh3
+
N
CH3
N
O
O
O
CH3
16 Z (a,b)
15
H
N
E1
N
C
CH3
N
E2
N
O
O
CH3
16
E1
a
b
CO2Me
16 E (a,b)
Ph
E2 CO2Et CO2Me
phosphorane 14 (Scheme 1). SiO2 powder was found to
catalyze conversion of the compound 14 to electron-poor
N-vinyl imidazoles 16(a–b) in solvent-free conditions [23]
under thermal (90 ꢁC, 1 h) conditions. In the absence of the
SiO2 powder, the reaction time for the conversion of the
compound 14a to electron-poor N-vinyl imidazole 16a
amounted to 48 h at 90 ꢁC. In the absence of the SiO2
powder, the conversion of the zwitterionic intermediate
14b to electron-poor N-vinyl imidazole 16b was not
observed and decomposition of the starting materials was
observed in 48 h at 90 ꢁC (Scheme 2). The reaction pro-
ceeds smoothly and cleanly under mild conditions and no
side reactions were observed. The mechanism of the
reaction has not been established experimentally. However,
a possible explanation [24] is proposed in Scheme 2. The
NMR spectra indicated that solutions of compound 16(a–b)
contain two isomers (E and Z). The relative percentages of
1
rotamers of 16a–b in CDCl3 were determined from the H
NMR spectra. The structures 8(a–b) and 16(a–b) were
1
deduced from their IR, H and 13C NMR spectra.
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J Chem Crystallogr (2011) 41:1376–1385
1379
8a
E
-16a
Z
-16a;
Z
-16a;
molecule A
molecule B
Fig. 1 Molecular structures of compounds 8a, E-16a and Z-16a (two
crystallographically independent molecules A and B) with the atom
numbering schemes and intramolecular C–H_O/N contacts forming
S(5) and S(6) motifs, respectively (dashed lines). For Z-16a molecule
A with -x, -y, -z atomic coordinates is shown for comparison with
molecule B. Disorder of one of the methyl groups and the ester
moiety in molecule B is shown. Displacement ellipsoids represent the
50% probability level
Table 1 Selected interatomic
˚
distances (A) and torsion angles
8a
Z-16a
E-16a
(ꢁ) of 8a, Z-16a and E-16a
Molecule A
Molecule B
Bond lengths
N(7)–C(7)
1.433(2)
1.433(3)
1.335(3)
1.482(4)
1.467(3)
1.436(3)
1.340(4)
1.495(4)
1.471(4)
1.436(2)
C(7)–C(10)
1.324(2)
1.491(2)
–
1.339(2)
1.501(2)
1.472(2)
C(7)–C(17)
C(10)–C(11)
Torsion angles
C(18)–O(4)–C(17)–C(7)
C(17)–O(4)–C(18)–C(19)
176.34(10)
180.0(2)
167.2(3)
-91.4(3)
0.2(4)
172.4(5)
-169.5(9)a
85.3(3)
176.58(9)
-83.55(13)
126.66(11)
172.70(10)
153.93(11)
133.13(12)
–
C(5)–N(7)–C(7)–C(10)
113.09(14)
a
N(7)–C(7)–C(10)–C(11)
C(10)–C(7)–C(17)–O(3)
C(7)–C(10)–C(11)–C(12)
–
170.11(12)
–
3.0(4)
In the disordered region the
respective C(17B)–O(4B)–
C(18C)–C(19C) torsion angle is
-115.6(11)ꢁ
168.0(3)
-174.6(3)
-174.7(3)
175.5(3)
Crystal Structures of Compounds 8a, Z-16a and E-16a
described by us previously and deposited at the Cambridge
Structural Database [25]. The molecules A and B of Z-16a
adopt Z geometry with respect to the double bond
C(7)=C(10), which is reflected in the value of the torsion
angle N(7)–C(7)–C(10)–C(11) of 0.2(4)ꢁ and 3.0(4)ꢁ for
A and B, respectively (Table 1). The molecule in E-16a is
E isomer with respect to C(7)=C(10) with the N(7)–C(7)–
C(10)–C(11) torsion angle of 172.7(1)ꢁ.
The crystals of 8a, Z-16a and E-16a are built up from
molecules shown in Fig. 1. In all 8a, Z-16a and E-16a the
carbonyl atom O(3) of the ester group is in antiperiplanar
conformation in relation to the vinyl atom C(10) [see the
O(3)–C(17)–C(7)–C(10) torsion angles in Table 1], as
previously found in most of the related compounds
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J Chem Crystallogr (2011) 41:1376–1385
The overall geometries of both crystallographically
C(8)–H(8)_O(6)ii and C(10)–H(10A)_O(3)ii bonds to
form helical chains along the b-axis (Fig. 3). The adjacent
chains interact with each other via C(10)–H(10B)_N(9)iv
and C(18)–H(18B)_O(6)v contacts, giving rise to layers
independent molecules A and B of Z-16a and that of 8a
seem to be similar to each other, and additionally similar to
that observed in the structurally related compounds [25].
Like previously observed, two planes (with the atoms N(7)
and C(7) being common) may be distinguished in the
molecules of 8a and Z-16a: plane 1 including methyl- or
ethylacrylate moiety, atom N(7) and phenyl ring in Z-16a,
and plane 2 including theophylline part and atom C(7). The
dihedral angles between the least-squares planes 1 and 2 in
both molecules of Z-16a (87.3(1)ꢁ for A and 84.5(1)ꢁ for
B) reveal that the two planes are almost perpendicular to
each other, whereas the same angle in 8a is only 69.6(1)ꢁ.
The C(11) * C(16) phenyl ring in both A and B of Z-16a
is only slightly twisted (see C(7)–C(10)–C(11)–C(12) tor-
sion angles in Table 1), which was also previously
observed in most of the Z geometrical isomers of similar
structures [25]. Some more significant deviation from the
planarity is observed in the ester methyl group of Z-16a, as
seen from C(17)–O(4)–C(18)–C(19) torsion angles of
167.2(3)ꢁ for molecule A and -169.5(9)ꢁ for molecule
B. It is to be noted that the unusually high deviation is
observed in the disordered region of the molecule
B denoted in Fig. 1 as C(18C) and C(19C) with s.o.f. =
0.47(2), as seen from C(17B)–O(4B)–C(18C)–C(19C)
torsion angle of -115.6(11)ꢁ.
ꢀ
parallel to ð101Þ plane (Fig. 3). Additional stabilization of
the layer structure is provided by the weak C(3)–
H(3A)_p[Cg(1)]xv contacts, and the inter-layer interac-
tions are realized through stacking p[Cg(2)]_p[Cg(2)]iii
interactions (Table 3). These, in combination with weaker
C–H_O contacts result in a three-dimensional network of
interactions in the crystal of 8a.
Three different types of C–H_O/N intermolecular
interactions are observed in the crystal lattice of Z-16a:
between A molecules, between B molecules, and between
A and B molecules (Fig. 4). In the A_A contacts the
main role is played by the centrosymmetric bifurcated
bonds with atom O(6A) acting as acceptors, which are
additionally stabilized by the C–H_p interactions, as
shown in Fig. 4a. The more numerous B_B contacts are
realized mainly via two different types of the centro-
symmetric bonds and additional C(3B)–H(3BC)_O(3B)vi
interactions, as shown in Fig. 4b. The respective
A_A and B_B connections are formed in bc plane and
result in two types of ‘‘layers’’ parallel to (100) plane: at
x = 1/2, 3/2,…, and at x = 0, 1,… for ‘‘layer’’ A and
‘‘layer’’ B, respectively. The inter-layer contacts are
provided by the A_B interactions, which are C(8A)–
H(8A)_N(9B), C(8B)–H(8B)_O(4A) and C(1B)–
H(1BC)_O(2A)viii bonds, as shown in Fig. 4c, giving
rise to a three-dimensional network of interactions in the
crystal of Z-16a.
Like previously observed in the structurally related
compounds [25], in both A and B of Z-16a the
weak intramolecular contacts formed in plane 1: C(10)–
H(10)_O(4) and C(16)–H(16)_N(7), give rise to respec-
tively five-membered S(5) and six-membered S(6) motifs
(Fig. 1; Table 2). The close C–H_N contacts are accom-
panied by the intramolecular C(16)–H(16)_p[Cg(1)]
interactions of the geometry given in Table 3.
The molecules of E-16a in its crystal interact with each
other via centrosymmetric C(8)–H(8)_O(3)iii and C(10)–
H(10)_O(2)ix bonds (Table 2) and p_p: Cg(1)_Cg(2)ix
and Cg(2)_Cg(2)ix stacking interactions (Table 3) to form
ribbons running down the a-axis, shown in Fig. 5. Weaker
C–H_O contacts provide the inter-layer interactions and
additional stabilization of a three-dimensional crystal
structure of E-16a.
Quite different geometry is observed in the molecule of
E isomer present in E-16a. Here the ethyl 3-phenylacrylate
moiety is not planar and both the phenyl and ester groups
are twist relative to the plane defined by the atoms C(17),
C(7), C(10), C(11) and N(7). That is reflected in the values
of the following torsion angles: C(7)–C(10)–C(11)–C(12)
(133.1(2)ꢁ), C(10)–C(7)–C(17)–O(3) (153.9(1)ꢁ) and
C(17)–O(4)–C(18)–C(19) (-83.6(2)ꢁ). Due to such a huge
difference in the molecular conformation (shown in
Fig. 2), none of described above intramolecular interac-
tions observed in the molecules A and B of Z-16a are
possible in the molecule of E isomer in E-16a.
Conclusion
In conclusion, we have developed a convenient, one-pot
regio- and stereoselective method for preparing electron-
poor imidazoles 8(a–b) and 16(a–b) utilising in situ gen-
eration of the phosphonium salts. The crystal structures for
both Z and E isomers of 16a as well as for 8a have been
determined. The influence of the phenyl group and its
orientation with respect to the double bond on the molec-
ular geometry has been discussed.
The crystal packing diagrams of 8a, Z-16a and E-16a
are dominated by weak C–H_O contacts (Table 2).
Important role is also played by the C–H_N interactions
(Table 2) and C–H_p and p_p contacts summarized in
Table 3. In the crystal lattice, the molecules of 8a related
by the action of 21 axis are joined to each other by
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J Chem Crystallogr (2011) 41:1376–1385
1381
Table 2 Geometry of proposed
C–H_O/N close contacts for
8a, Z-16a and E-16a
˚
D–H (A)
˚
˚
Compound
D–H_A
H_A (A)
D_A (A)
D–H_A (ꢁ)
8a
C(1)–H(1B)_O(2)
C(1)–H(1C)_O(3)i
0.99(2)
0.97(2)
0.97(2)
0.97(2)
0.98(2)
0.98(2)
0.97(2)
0.92(2)
1.00(3)
0.99(3)
0.95(2)
1.02(2)
0.98(2)
0.98(2)
1.00(3)
1.01(2)
1.02(3)
1.02(3)
0.96(3)
0.98
2.30(2)
2.68(2)
2.35(2)
2.37(2)
2.64(2)
2.46(2)
2.50(2)
2.46(2)
2.28(3)
2.35(3)
2.56(2)
2.40(2)
2.40(2)
2.36(2)
2.63(3)
2.43(2)
2.65(3)
2.26(3)
2.50(3)
2.53
2.713(2)
3.607(2)
2.771(2)
3.278(2)
3.173(2)
3.264(2)
3.388(2)
3.379(2)
2.755(4)
3.269(4)
2.944(4)
3.382(4)
2.760(3)
3.320(4)
3.535(4)
3.062(4)
3.617(4)
2.716(4)
3.122(4)
2.934(4)
3.256(3)
2.750(3)
3.421(3)
3.339(3)
2.743(3)
3.399(4)
3.499(4)
3.625(4)
3.460(4)
3.255(4)
3.053(4)
3.314(4)
3.560(8)
2.757(2)
2.955(2)
3.502(2)
3.133(2)
3.360(2)
3.287(2)
3.297(2)
3.334(2)
104(2)
162(2)
105(2)
156(2)
115(2)
140(2)
152(2)
176(2)
108(2)
154(2)
104(2)
160(2)
101(2)
168(2)
151(2)
120(2)
159(2)
106(2)
122(2)
105
C(3)–H(3B)_O(2)
C(8)–H(8)_O(6)ii
C(10)–H(10A)_O(2)iii
C(10)–H(10A)_O(3)ii
C(10)–H(10B)_N(9)iv
C(18)–H(18B)_O(6)v
C(1A)–H(1AB)_O(6A)
C(3A)–H(3AA)_O(3A)vi
C(3A)–H(3AC)_N(9A)
C(8A)–H(8A)_N(9B)
C(10A)–H(10A)_O(4A)
C(10A)–H(10A)_O(6A)iii
C(12A)–H(12A)_O(6A)iii
C(16A)–H(16A)_N(7A)
C(19A)–H(19B)_O(3A)vii
C(1B)–H(1BB)_O(2B)
C(1B)–H(1BC)_O(2A)viii
C(3B)–H(3BD)_N(9B)
C(3B)–H(3BC)_O(3B)vi
C(3B)–H(3BA)_O(2B)
C(3B)–H(3BF)_N(1B)ix
C(8B)–H(8B)_O(4A)
C(10B)–H(10B)_O(4B)
C(10B)–H(10B)_O(6B)x
C(12B)–H(12B)_O(6B)x
C(13B)–H(13B)_O(2B)xi
C(14B)–H(14B)_N(1B)xi
C(15B)–H(15B)_O(2B)ix
C(16B)–H(16B)_N(7B)
C(16B)–H(16B)_O(2B)ix
C(19B)–H(19E)_O(3B)vii
C(1)–H(1B)_O(6)
Z-16a
0.98
2.28
172
0.98
2.34
104
0.98
2.50
157
1.04(2)
0.97(3)
0.97(3)
0.94(2)
1.00(3)
1.01(3)
1.01(3)
0.99(2)
0.99(2)
0.98
2.35(2)
2.36(2)
2.45(3)
2.64(2)
2.68(3)
2.70(3)
2.52(3)
2.42(2)
2.67(3)
2.66
158(2)
103(2)
164(2)
151(2)
157(2)
133(2)
130(2)
121(2)
123(2)
154
Symmetry codes: (i) -x ? 3/2,
y - 1/2, -z ? 1/2; (ii) -x ? 3/
2, y ? 1/2, -z ? 1/2; (iii)
-x ? 1, -y ? 1, -z ? 1; (iv)
x - 1/2, -y ? 3/2, z - 1/2;
(v) -x ? 1, -y ? 1, -z; (vi) x,
-y ? 1/2, z ? 1/2; (vii) x,
-y ? 1/2, z - 1/2; (viii) x - 1,
y, z - 1; (ix) -x, -y ? 1,
-z ? 1; (x) -x, -y ? 1, -z;
(xi) -x, y ? 1/2, -z ? 1/2;
(xii) -x, -y, -z ? 1; (xiii) x,
y ? 1, z; (xiv) -x ? 1,
E-16a
0.96(2)
1.00(2)
0.95(2)
0.96(2)
0.99(2)
0.96(2)
0.98(2)
0.95(2)
2.31(2)
2.50(2)
2.66(2)
2.38(2)
2.43(2)
2.66(2)
2.66(2)
2.65(2)
108(2)
107(1)
147(2)
135(1)
157(1)
124(1)
123(1)
129(1)
C(3)–H(3A)_N(9)
C(3)–H(3B)_O(2)xii
C(8)–H(8)_O(3)iii
C(10)–H(10)_O(2)ix
C(13)–H(13)_O(3)xiii
C(14)–H(14)_O(3)xiii
C(18)–H(18A)_O(4)xiv
-y ? 2, -z
Preparation of Alkyl 2-(1,3-dimethyl-2,6-dioxo-1,2,3,
Experimental
6-tetrahydro-7H-purin-7-yl)acrylate (8(a–b))
Melting points were measured on an Electrothermal 9100
apparatus and are uncorrected. Elemental analyses were per-
formed using a Heraeus CHN-O-Rapid analyzer. IR spectra
To a magnetically stirred solution of triphenylphosphine
(0.262 g, 1 mmol) and theophylline (0.18 g, 1 mmol) in
dichloromethane (5 mL) was added dropwise a mixture of
alkyl acetylenecarboxylates 2 (1 mmol) in dichlorometh-
ane (2 mL) at -10 ꢁC over 15 min. The mixture was
1
were recorded on a Shimadzu IR-460 spectrometer. H and
13C NMR spectra were measured with a Bruker Spectrospin
spectrometer at 250 and 62.5 MHz, respectively.
123

1382
J Chem Crystallogr (2011) 41:1376–1385
Table 3 Geometry of proposed C–H_p and p_p interactions for 8a, Z-16a and E-16a
˚
C–H (A)
˚
˚
Compound
C–H_p/p_p
H_p (A)
C_p (A)
C–H_p (ꢁ)
˚
p_p (A)
8a
C(3)–H(3A)_Cg(1)xv
Cg(2)_Cg(2)iii
0.98(2)
–
2.70(2)
–
3.539(2)
3.557(2)
3.550(4)
3.522(3)
3.595(4)
3.452(3)
3.413(8)
3.550(2)
3.560(2)
3.595(2)
144(2)
–
Z-16a
C(3A)–H(3AB)_Cg(2A)xvi
C(16A)–H(16A)_Cg(1A)
C(18A)–H(18A)_Cg(3A)iii
C(16B)–H(16B)_Cg(1B)
C(18C)–H(18E)_Cg(3B)x
C(13)–H(13)_Cg(2)xiii
Cg(1)_Cg(2)ix
0.98(3)
1.01(2)
1.00(3)
0.99(2)
0.99
2.85(3)
2.64(2)
2.67(3)
2.58(2)
2.77
130(2)
146(2)
154(2)
148(2)
123
E-16a
0.96(2)
–
2.80(2)
–
136(2)
–
Cg(2)_Cg(2)ix
–
–
–
Symmetry codes: (iii) -x ? 1, -y ? 1, -z ? 1; (ix) -x, -y ? 1, -z ? 1; (x) -x, -y ? 1, -z; (xiii) x, y ? 1, z; (xv) -x ? 2, -y ? 1,
-z ? 1; (xvi) -x ? 1, -y ? 1, -z ? 2; Cg(1), Cg(2) and Cg(3) are the centroids of C(4) * N(9), N(1) * C(6) and C(11) * C(16) rings,
respectively
Fig. 2 Comparison of molecular structures of compounds 8a (thin
line), E-16a (open line) and Z-16a (two crystallographically
independent molecules shown with solid line) [A least-squares fit
using the OFIT instruction in XP program; the common reference
points are N(7), C(7) and C(10) atoms.]
Fig. 3 Arrangement of the molecules 8a in the crystal lattice
showing two adjacent helical chains along b-axis (solid and open
allowed to warm up to room temperature. Silica gel powder
(1.5 g) was added and the solvent was evaporated. Dry
silica gel and the residue were heated for 1 h at 90 ꢁC and
then placed over a column of silica gel powder (12 g). The
column chromatography was washed using ethyl acetate-
light petroleum ether (3:10) as eluent. The solvent was
removed under reduced pressure and the products were
obtained as colorless crystals.
lines) interacting with each other via C–H_O/N contacts (dashed
ꢀ
lines) to form layers parallel to ð101Þ plane. Symmetry codes are
given in Table 2
7.63 (1s, 1H, imidazole). 13C NMR (CDCl3): dC = 28.07
and 29.66 (2CH3); 53.23 (OCH3); 107.94, 133.39 and
148.74 (3C); 123.69 (=CH2); 140.95 (CH imidazole);
151.60 and 154.47 (2C=O of amide); 162.33(C=O of ester).
C11H12N4O4 (264.24): calcd. C, 50.00; H, 4.58; N, 21.20;
found C, 49.96; H, 4.55; N, 21.17.
Selected Data for Methyl 2-(1,3-dimethyl-2,6-dioxo-
Preparation of Single Crystals of Methyl
2-(1,3-dimethyl-2,6-dioxo-1,3,3,6-tetrahydro-
7H-purin-7-yl)acrylate (8a)
1,3,3,6-tetrahydro-7H-purin-7-yl)acrylate (8a)
Colorless crystals. Yield: 0.238 g (90%). mp 160–163 ꢁC.
IR (KBr): m = 2953, 1707, 1669, 1453, 1230 cm-1. H
1
Colorless single crystals of 8a were obtained from slow
evaporation of its dichloromethane/light petroleum ether
NMR (CDCl3): dH = 3.36, 3.60 (2s, 6H, 2CH3); 3.86 (1s,
3H, OCH3); 5.99–6.51 (d of d, 2H, JHH = 1 Hz, =CH2);
2
123

J Chem Crystallogr (2011) 41:1376–1385
1383
(a)
(b)
Fig. 5 Arrangement of the molecules E-16a within the ribbon along
a-axis formed by the centrosymmetric C–H_O bonds (dashed lines)
and p_p stacking interactions (dashed open). Symmetry codes are
given in Table 2
(c)
and 154.46 (2C=O of amide); 161.82 (C=O of ester).
C12H14N4O4 (278.26): calcd C, 51.80; H,5.07; N,20.13;
found C,51.77; H,5.03; N,20.11.
Selected Data for Ethyl (Z,E)-2-(1,3-dimethyl-2,
6-dioxo-1,3,3,6-tetrahydro-7H-purin-7-yl)-3-phenyl-
2-peropenoate (16a)
Fig. 4 Three types of intermolecular interactions in Z-16a:
a between A molecules, b between B molecules, and c between
A and B molecules. C–H_O/N contacts are shown with dashed lines,
p_p stacking interactions with dashed open. Intramolecular contacts
are not shown for clarity. Symmetry codes are given in Table 2
Colorless crystals. Yield: 0.343 g (97%); mp: 145–148 ꢁC.
IR (KBr): m = 2946, 1707, 1661, 1453, 1269 cm-1. H
1
NMR (CDCl3, %E = 40 and %Z = 60) for Z: dH = 1.28
(1t, 3H, 3JHH = 7 Hz, CH3); 3.31 and 3.58 (2s, 6H, 2CH3);
3
4.29 (q, 2H, JHH = 7 Hz, OCH2); 6.93(d, 2H,
3JHH = 7.25 Hz, arom); 7.20–7.29 (m, 3H, arom); 7.40
(1s, 1H, imidazole); 7.89 (1s, 1H, =CH); 13C NMR
(CDCl3) for Z: dC = 14.13, 27.95 and 29.91 (3CH3); 62.28
(OCH2); 129.11, 129.70, 130.90, 138.66 and 141.19 (7CH);
107.39, 123.77, 131.06 and 148.68 (5C); 151.64 and
(1:3) solution (20–25 ꢁC). The colorless single crystals
were filtered off, washed with a cold mixture of dichloro-
methane/light petroleum ether (1:3) and dried at room
temperature (mp 160–163 ꢁC).
1
154.24 (2C=O of amide); 163.10 (C=O of ester). H NMR
Selected Data for Ethyl 2-(1,3-dimethyl-2,6-dioxo-
(CDCl3, %E = 40 and %Z = 60) for E: dH = 1.59 (1t, 3H,
3JHH = 7.25 Hz, CH3); 3.40 and 3.65 (2s, 6H, 2CH3); 4.25
1,3,3,6-tetrahydro-7H-purin-7-yl)acrylate (8b)
3
(q, 2H, JHH = 7 Hz, OCH2); 7.30(1s, 1H, =CH); 7.34–
Colorless crystals. Yield: 0.236 g (85%); mp143–146 ꢁC
7.77 (m, 5H, arom); 7.81 (1s, 1H, imidazole); 13C NMR
(CDCl3) for E: dC = 13.55,28.07 and 29.90 (3CH3); 62.02
(OCH2); 128.38, 129.70, 131.98, 132.14 and 141.58 (7CH);
107.96, 125.96, 137.02 and 148.75 (4C); 151.61 and
154.50 (2C=O of amide); 162.75 (C=O of ester).
C18H18N4O4 (354.13): calcd C, 61.01; H, 5.12; N, 15.81;
found C, 60.07; H, 5.08; N, 15.78.
IR (KBr): m = 2984, 1715, 1676, 1453, 1230 cm-1. H
1
NMR (CDCl3): dH = 1.27 (1t, 3H, 3JHH = 7.25 Hz, CH3);
3.38, 3.62 (2s, 6H, 2CH3); 4.29 (q, 2H, JHH = 7 Hz,
3
2
OCH2); 5.99–6.52 (d of d, 2H, JHH = 1 Hz, =CH2); 7.63
(1s, 1H, imidazole). 13C NMR (CDCl3): dC = 14.04, 28.07
and 29.66 (3CH3); 62.55 (OCH2); 107.97, 133.62 and
148.73 (3C); 123.42 (=CH2); 141 (CH imidazole); 151.64
123

1384
J Chem Crystallogr (2011) 41:1376–1385
Preparation of Single Crystals Of Ethyl (Z,E)-2-
(1,3-dimethyl-2,6-dioxo-1,3,3,6-tetrahydro-7H-purin-
7-yl)-3-phenyl-2-peropenoate (16a)
Selected Data for Dimethyl (Z,E)-2-(1,3-dimethyl-2,
6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)butenedioate
Viscous yellow oil, Yield: 0.258 g 80% IR (Neat):
m = 3115, 2953, 1715, 1669, 1230 and 1276. 1H NMR
(CDCl3, %E = 21 and %Z = 79) for Z: dH = 3.32 and
3.60 (2s, 6H, 2CH3), 3.69 and 3.83 (2s, 6H, 2OCH3), 7.67
(1s, 1H, =CH), 7.11 (1s, 1H, imidazole).13C NMR (CDCl3)
for Z dC: 28.03 and 30.03 (2CH3), 52.67 and 53.88
(2OCH3), 102.84, 134.19 and 148.47 (3C), 125.43 (=CH),
Colorless single crystals of 16a were obtained from slow
evaporation of its dichloromethane/light petroleum ether
(1:2) solution (20–25 ꢁC). The colorless single crystals
were filtered off, washed with a cold mixture of dichloro-
methane/light petroleum ether (1:2) and dried at room
temperature (mp 145–148 ꢁC).
Table 4 Experimental data for 8a, Z-16a and E-16a
8a
Z-16a
E-16a
Empirical formula
Formula weight (g mol-1
Crystal system
C11H12N4O4
264.25
C18H18N4O4
354.36
C18H18N4O4
354.36
)
Monoclinic
P21/n
Monoclinic
P21/c
Triclinic
ꢀ
P1
Space group
˚
a (A)
8.679(2)
10.799(3)
12.356(3)
16.372(3)
17.305(3)
13.147(3)
9.531(3)
9.593(2)
10.776(3)
67.93(3)
68.93(3)
86.48(3)
848.9(4)
2
˚
b (A)
˚
c (A)
a (ꢁ)
b (ꢁ)
c (ꢁ)
94.10(3)
111.67(3)
3
˚
V (A )
1155.1(5)
4
3461.5(12)
8
Z
Dcalc (g cm-3
)
1.519
1.360
1.386
l (mm-1
)
0.12
0.10
0.10
F(000)
552
1488
372
Crystal size (mm)
Crystal colour
Crystal form
0.32 9 0.13 9 0.10
Colourless
Needle
0.25 9 0.22 9 0.11
Colourless
Block
0.60 9 0.33 9 0.14
Colourless
Plate
˚
Radiation type, k (A)
T (K)
Mo Ka, 0.71073
100(2)
Mo Ka, 0.71073
100(2)
Mo Ka, 0.71073
100(2)
h Range (ꢁ)
h, k, l range
2.78–36.87
-14 B h B 14
-15 B k B 18
-20 B l B 20
20051
2.88–27.00
-16 B h B 20
-22 B k B 21
-16 B l B 16
24094
3.39–37.49
-15 B h B 13
-15 B k B 16
-18 B l B 17
12510
Measured reflections
Independent reflections
5372
7549
6793
Observed reflections (I [ 2r(I))
Rint
3098
3961
4039
0.047
F2
0.067
F2
0.029
F2
Refinement on
Data/restraints/parameters
R1; wR2 (F2o [ 2r(F2o))
R1; wR2 (all data)
GooF = S
5372/0/220
0.044; 0.106
0.098; 0.140
1.034
7549/9/598
0.069; 0.100
0.159; 0.116
1.022
6793/0/307
0.045; 0.101
0.081; 0.108
1.009
Weighting parameter a; b
ꢁ
R1 ¼ jjFoj ꢁ jFcjj= jFoj; wR2 ¼
P = (F2o ? 2F2c)/3
0.0699; 0.0695
0.51; -0.28
0.0374; 0.0
0.20; -0.24
0.0480; 0.0
0.44; -0.30
ꢀ
ꢁ3
˚
Dqmax; Dqmin e A
pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
P
P
P
P
½wðFo2 ꢁ Fc2Þ ꢂ= ½wðFo2Þ ꢂ; weighting scheme: w = 1/[r2(F2o) ? (aP)2 ? bP], where
2
2
123

J Chem Crystallogr (2011) 41:1376–1385
1385
142.44 (CH imidazole), 151.57 and 154.55 (2C=O of
amid), 162.14 and 162.80 (2C=O of ester). 1H NMR
(CDCl3, %E = 21 and %Z = 79) for E: dH = 3.35 and
3.58 (2s, 6H, 2CH3), 3.78 and 3.83 (2s, 6H, 2OCH3), 6.64
(1s, 1H, =CH), 7.72 (1s, 1H, imidazole).13C NMR (CDCl3)
for E dC = 28.26 and 30.03 (2CH3), 52.72 and 53.64
(2OCH3), 104.02, 134.19 and 148.47 (3C), 123.03 (=CH),
141.11 imidazole), 151.57 and 154.55 (2C=O of amid),
162.14 and 162.80 (2C=O of ester). C13H14N4O6 (322.27):
C, 48.45; H, 4.38; N, 17.38; O, 29.79; found: C, 48.40; H,
4.33; N, 17.35; O, 29.75.
Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif by quoting the deposition numbers CCDC-
809464 (for 8a), CCDC-809465 (for Z-16a) and CCDC-
809466 (for E-16a).
References
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The crystallographic measurements of 8a, Z-16a and
E-16a were performed on a j-geometry KUMA KM4CCD
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˚
chromatized MoKa radiation (k, 0.71073 A). The data for
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tropic thermal parameters for non-H atoms. The ester ethyl
group in the molecule B of Z-16a is disordered over two
sites with s.o.f. = 0.53(2) for C(18B), C(19B) and 0.47(2)
for C(18C), C(19C). Geometrical restraints (SAME
instructions) were applied to the disordered region, and the
two positions of atom O(4) in B [O(4B) and O(4C)] were
constrained (using EXYZ and EADP) to have the same
positional and displacement parameters. All H atoms were
found in difference Fourier maps, which showed that the
methyl H atoms on atom C(3B) in Z-16a were disordered
equally over two sites, therefore this methyl group was
refined with AFIX 127 instruction. H atoms in the disor-
dered regions of molecule B in Z-16a were treated as riding
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Lis T, Ramazani A (2007) Z Naturforsch 62b:829–834
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(2007) Phosphorus Sulfur Silicon 182:413–417
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CSD refcodes: EDOSUM, YINGAE, KITNIL, KITNOR
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˚
atoms, with C–H distances of 0.98–0.99 A, and with
U
iso(H) values of 1.2Uiso(C) for CH2 groups and 1.5Uiso(C)
for CH3 groups. The remaining H atoms in 8a, Z-16a and
E-16a were refined isotropically. Figures were made with
the XP program [28]. A summary of the conditions for the
data collection and the structure refinement parameters are
given in Table 4. Further details on the crystal structures
investigations may be obtained from The Cambridge
123