Nucleophilic substitution approach towards 1,3-dimethylbarbituric acid derivatives - New synthetic routes and crystal structures

Article abstract of DOI:10.1016/j.tet.2011.11.093

We describe simple, convenient and high-yielding nucleophilic substitution reactions to synthesize new derivatives of 1,3-dimethylbarbituric acid (1a). Based on its active C5 position, condensing 1a with sulfuryl chloride gives the corresponding 5,5-dichloro-1,3-dimethylbarbituric acid (13). The latter was reacted with silver nitrite and potassium cyanide to afford 5-chloro-5-nitro-1, 3-dimethylbarbituric acid (14) and 5-cyano-1,3-dimethylbarbiturate (17), respectively. Furthermore, by employing the nucleophilic character of 2,3-dihydro-1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene (8) the obtained compounds 13 and 14 have been converted to 2-chloro-1,3-diisopropyl-4,5- dimethyl-1H-imidazol-3-ium-1,3-dimethyl-5-nitro-1,3-dimethylbarbiturate (18) and 1,3-dimethylbarbituric acid trimer (21), respectively. X-ray structures for compounds 13, 14, 17, 18 and 21 were determined.

Full text of DOI:10.1016/j.tet.2011.11.093

Tetrahedron 68 (2012) 1005e1010
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Nucleophilic substitution approach towards 1,3-dimethylbarbituric acid
derivativesdnew synthetic routes and crystal structures
a
b
c
d
d,
*
€
Eyad Mallah , Kamal Sweidan , Jorn Engelmann , Manfred Steimann , Norbert Kuhn
,
Martin E. Maier e
,
*
a Faculty of Pharmacy and Medical Sciences, Petra University, PO Box 961343 Amman 11196, Jordan
b Department of Chemistry, Faculty of Science, The University of Jordan, Amman, Jordan
c
€
Max Planck Institute for Biological Cybernetics, Spemannstrasse 41, Tubingen, Germany
Institut fur Anorganische Chemie der Universitat Tubingen, Auf der Morgenstelle 18, 72076 Tubingen, Germany
Institut fur Organische Chemie der Universitat Tubingen, Auf der Morgenstelle 18, 72076 Tubingen, Germany
d
€
€
€
€
e
€
€
€
€
a r t i c l e i n f o
a b s t r a c t
Article history:
We describe simple, convenient and high-yielding nucleophilic substitution reactions to synthesize new
derivatives of 1,3-dimethylbarbituric acid (1a). Based on its active C5 position, condensing 1a with
sulfuryl chloride gives the corresponding 5,5-dichloro-1,3-dimethylbarbituric acid (13). The latter was
reacted with silver nitrite and potassium cyanide to afford 5-chloro-5-nitro-1,3-dimethylbarbituric acid
(14) and 5-cyano-1,3-dimethylbarbiturate (17), respectively. Furthermore, by employing the nucleophilic
character of 2,3-dihydro-1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene (8) the obtained compounds 13
and 14 have been converted to 2-chloro-1,3-diisopropyl-4,5-dimethyl-1H-imidazol-3-ium-1,3-dimethyl-
5-nitro-1,3-dimethylbarbiturate (18) and 1,3-dimethylbarbituric acid trimer (21), respectively. X-ray
structures for compounds 13, 14, 17, 18 and 21 were determined.
Received 4 November 2011
Received in revised form 28 November 2011
Accepted 29 November 2011
Available online 4 December 2011
Keywords:
Barbituric acids
Nucleophilic carbenes
Heterocycles
Substitution reaction
Trimerization
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
Because of the strongly basic character of N-heterocyclic car-
benes (8)17e19 (Fig. 2) they react immediately with Bronsted acids
Barbituric acids (1) are heterocyclic derivatives of pyrimidine
trione.1e3 They are well-known in medicinal chemistry as hyp-
notics, sedatives, anticonvulsants and anxiolytic agents.4e6 Re-
cently, barbiturates have been used to induce anaesthesia in
surgery procedures.7 C5-substituted and disubstituted barbituric
and 2-thiobarbituric acids exhibit a wide spectrum of biological
activity and some of them are useful drugs or agrochemicals.8,9 The
C5 position in 1 is an active site since it could be acting as elec-
trophilic and nucleophilic centres.10,11 As shown in Fig. 1, com-
pounds 1e7 represent some known barbituric acid derivatives,12e16
which play an important role in pharmaceutical chemistry.
Over the last years our group (N. Kuhn) has studied reactions of
nucleophilic carbenes with various electrophiles. In this context we
became interested to react nucleophilic carbenes with barbituric
acid derivatives having an electrophilic centre at C5. However, this
would require an efficient and simple access to such compounds.
Our results in this area are described in this paper.
and have consequently been used as selective deprotonation re-
agents (compounds 9 and 10).20,21 Furthermore, they are utilized as
very useful nucleophiles to form stable charge transfer adducts
(compounds 11 and 12).22,23
O
R
R
O
O
O
O
R
R
N
N
N
N
N
N
N
N
N
N
H
H
O
NH2
H
O
N
O
H
O
H
1a (R = CH3)
2
3
Ph Ph
O
R
O
O
O
R
R
R
O
R
O
R
R
R
N
N
N
N
N
N
N
O
HO
O
O
O
O
Br Br
NO2
N
Ph
4
5
6
7
* Corresponding authors. Tel.: þ49 7071 2975247; e-mail addresses: norbert.-
kuhn@uni-tuebingen.de (N. Kuhn), martin.e.maier@uni-tuebingen.de (M.E. Maier).
Fig. 1. Structures of some barbituric acid derivatives (R: H or alkyl).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.11.093

1006
E. Mallah et al. / Tetrahedron 68 (2012) 1005e1010
2.1.1. The utility of 13 with ambident nucleophiles. 2.1.1.1. With ni-
O
S
trite anion to form compound 14. The 5,5-disubstituted barbituric
acids were pursued further where compound 13 underwent nu-
cleophilic substitution reactions with nitrite and cyanide.
O
O
O
N
N
N
N
N
N
N
H
H
In this work, the nucleophilic substitution of one Cl-atom in 13
was achieved under dry conditions by reacting 13 with silver nitrite
in dry acetonitrile via an SN2-like mechanism to afford compound
14. In spite of an excess amount of nitrite anion, only one Cl-atom
was replaced by a nitro group. The selection of acetonitrile was
based on complete miscibility of both reactants, which may lead to
high yield of product. On the other hand, dichloromethane solvent
was employed in the purification step to get rid of the excess
unreacted silver nitrite. Ziegler and Kappe and Biltz and Sedlat-
scheck prepared the related compound 15 (Scheme 1) by reacting
5-nitrobarbituric acid with hydrogen peroxide and concentrated
hydrochloric acid29 or with chlorine in water.30 However, in both
procedures an aqueous medium was present in the reaction vessel,
which led to a partial degradation of 15.
8
9
10
F
F
F
F
CN
N
N
N
BF4
F
N
CN
11
12
Fig. 2. Structures of some imidazole carbene derivatives.
In this study, we have investigated the reaction of dichlor-
obarbituric acid 13 with 2,3-dihydro-1,3-diisopropyl-4,5-
dimethylimidazol-2-ylidene (8), nitrite and cyanide anions. We
wish to describe herein a proposed mechanism for the synthesis of
1,3-dimethylbarbituric acid trimer (21). All the prepared com-
pounds were confirmed by NMR, elemental analysis, mass spec-
trometry and single-crystal X-ray diffraction.
Nucleophilic substitution by nitrite ion (ambident nucleophile)
at a saturated carbon atom (sp3) can give both the nitro compound
(RNO2) as well as the nitrite ester (RONO).31 X-ray structural
analysis of 14 shows the bonding to C5 is through nitrogen (N-at-
tack) rather than oxygen (O-attack) to the carbon since the softer
nitrogen of NOꢀ2 prefers to bind to a softer carbon in a tighter SN2
transition state. According to Kornblum’s rule, the more electro-
negative atom (hard base) in ambident nucleophiles reacts with
a carbon atom (hard acid) if the reaction mechanism is SN1-like
(carbocation formed), while for the tetravalent carbon (softer
acid) the less electronegative atom in the ambident nucleophiles
will do. Since the active carbon (C5) in 13 is flanked between two
carbonyl groups and attached to a high electronegative atom (Cl) it
is difficult for the reaction to proceed via an SN1 mechanism (for-
mation of a carbocation) even though Agþ is presented in the re-
action mixture. We note that the mechanism might also proceed in
a similar manner as illustrated in Scheme 2 (vide infra).
2. Results and discussion
2.1. Synthesis
It has long been known that nucleophilic substitution reactions
of 1,3-dimethylbarbituric acid (1a) having one or two leaving
groups at C5 give exclusive products in the C5 position.15,24,25 To
achieve this target, this study describes novel synthetic procedures
by employing various nucleophiles, the nature of the products
formed was dependent on the character of the used nucleophiles.
The preparation of 5,5-dichloro-1,3-dimethylbarbituric acid (13)
has been explored previously26e28 but low product yields and
limited access to starting materials have restricted the utility of
some of these procedures. One of these methods is based on the
reaction of synthesized tetramethyl alloxanthine with PCl5 in sym-
tetrachloroethane,26 another route depends on electrochemical
oxidation of 1a at a pyrolytic graphite electrode by a single volta-
metric peak at pH 1 in the presence of chloride ion.27 In addition,
reaction of 6-chloro-1,3-dimethyluracil with chlorine gas in pres-
ence of acetic acid and acetic anhydride was also reported.28
In our work, the preparation 13 was accomplished using a very
simple and efficient one-pot methodology. To realize the strategy
shown in Scheme 1, the two acidic hydrogen atoms at C5 in 1a were
readily substituted by chlorine atoms using 2 equiv of sulfuryl
chloride affording the respective product 13 inverygoodyield (85%).
H
H
O
O
H
OH
N
N
N
N
H
CN
O
O
N
CN
H
O
16
H3C
O
O
H3C
O
N
N
N
Cl
Cl
+
C
+ Cl C N
O
Cl
O
N
H3C
H3C
O
13
H3C
O
H3C
O
[K(18-crown-6)]+
CN
N
N
N
N
Cl
O
+
O
C
N
Cl
C N
+
CN
H3C
O
H3C
O
17
H3C
O
O
H3C
O
O
Scheme 2. The proposed mechanism for the formation of 17.
N
N
N
H
H
Cl
Cl
SO2Cl2 (2 eq.)
AgNO2
O
O
CH3CN, rt
(73%)
THF, 85 °C
6 h (85%)
N
H3C
H3C
O
1
13
2.1.1.2. With cyanide anion to form compound 15. Goutailler
et al.32 proposed the formation of 16 (Scheme 2) as an intermediate
in the photocatalytic degradation of dicyclanil. The molecule 16 was
also prepared in low yield by heating of ethyl cyanoacetate with
isocyanates in pyridine.33
In the present work, 18-crown-6 was employed to increase the
concentration of free cyanide anion, which substituted chlorine
atom via carbon atom (C-attack) and consequently enhancing the
H3C
O
H
N
N
Cl
NO2
Cl
O
O
NO2
N
N
H3C
O
H
O
14
15
Scheme 1. Synthesis of dichlorobarbituric acid 13 and its reaction with silver nitrite.

E. Mallah et al. / Tetrahedron 68 (2012) 1005e1010
1007
percent yield of 17. The proposed mechanism for the synthesis of 17
is shown in Scheme 2.
As depicted in Scheme 3, we propose the formation of 1,3-
dimethylbarbituric acid carbene intermediate in situ, which un-
dergoes trimerization to reach a stable form. The mechanism might
as well proceed via the monochloro anion. Washing the precipitate
with dichloromethane is necessary to get rid of the 2-
chloroimidazolium chloride (22). Interestingly, meldrum’s acid 23
(the analogue of barbituric acid carbene) is dimerized to 24
(Fig. 4).38 However, the target compound 21 was unambiguously
identified by single-crystal X-ray diffraction (Fig 7).
As a part of current studies on 1,3-dimethylbarbituric acid and
our interest in the chemistry of N-heterocyclic carbenes we next
turned our attention to use N-heterocyclic carbenes as an efficient
nucleophile. Accordingly, the 5-chloro-5-nitro-substituted barbi-
turic acid derivative 14 was then subjected to further nucleophilic
substitution with 8 in dry diethylether at ꢀ78 ꢁC to produce com-
pound 18 as colourless crystals in very good yield (86%) (Fig. 3).
Actually, based on the nucleophilic character of the N-heterocyclic
carbene either compound 19 or 20 was expected. The urea de-
rivative 20 would be the result of nucleophilic attack to the C4
carbonyl group of 14.34 The absence of formation of these com-
pounds may be attributed to steric repulsion between the oxygen
atoms (O4 and O6) of the pyrimidine moiety with the isopropyl
group of the nitrogen atoms in the imidazole moiety when imid-
azole carbene attempted to attack C5 in 14.
O O
O
O
O
O
O
O
O
O
H
H
O O
23
24
Fig. 4. The chemical structures of 23 and 24.
NO2
Cl
H3C
O
O
O
N
The analysis of 13C NMR data for 13, 14, 17 and 18 indicated that
the signal of C5 carbon is affected by the different substituents and
its hybridization. Accordingly, in compounds 13 and 14, the signals
of C5 carbon resonate at 72.2 and 89.2 ppm, respectively; this
downfielded chemical shift is attributed to the presence of strong
withdrawing groups at C5 position. This effect seems to be more
pronounced with the NO2-group in compound 14. Moreover, the
distinction between the 13C NMR signals for the corresponding C5
position of compounds 17 and 18 was easily accomplished due to
the highly upfielded chemical shift (41.4 ppm) relative to
(94.2 ppm), respectively.
N
NO2
N
Cl
Cl
O
N
N
N
O
N
N
N
H3C
O
N
O
O
CH3
N
O2N
O
N
18
19
20
CH3
Fig. 3. Chemical structures of 18, 19 and 20.
In the reaction of dichloro compound 13 with carbene 8 an
unexpected, formal trimerization of 1,3-dimethylbarbituric acid
carbene was observed (Scheme 3). Formation of the trimeric form
of 1,3-dimethylbarbituric acid was first reported by Poling et al.35,36
and Jursic and Stevens37 They carried out the reaction by using an
electro-oxidation method and by refluxing a solution of 5,5-
dibromo-1,3-dimethylbarbituric acid with 1,3-dibarbituric in
methanol for 4 days, respectively. None of them provided any
proposed mechanism. In the current work, we were delighted to
report a smooth one-pot synthesis of the trimer 21 by using N-
heterocyclic carbenes. Thus, treating 13 with 8 in dry diethylether
led to the formation of 21 in very good yield.
2.2. X-ray crystallography
The chemical structures of compounds 13, 14, 17, 18 and 21 were
determined by X-ray diffraction analysis. The obtained compounds,
besides 17, which crystallized in the orthorhombic space group,
crystallized in the monoclinic space group. The general view and
atom-numbering scheme for the molecules are shown in Figs. 5e7.
In molecule 13 (Fig. 5a) the Cl atoms attached to the C1 position
display some bond length disturbance [Cl(1)eC(1) 1.784(2) and
ꢀ
Cl(2)eC(1) 1.747(2) A]. The C(1)eC(4) bond length in 13 is consid-
erably longer than the corresponding bond length in 1a [1.53 vs
1.48 A].39 The bond angles in molecule 14 (Fig. 7b) clearly indicate
ꢀ
sp3-hybridization of the C1-carbon [N(3)eC(1)eCl(1) 110.8 (2)ꢁ].
The bond angle [Cl(1)eC(1)eN(3)] is larger than [Cl(1)eC(1)eCl(2)]
in molecule 13 by 5.1ꢁ. The geometry of the nitro group is as ex-
pected, having one shorter and one longer nitrogeneoxygen bond
O
H3C
N
CH3
N
O
H3C
O
O
H3
O
C
O
N
N
N
O
Et2O, –78 °C
(83%)
N
Cl
Cl
ꢀ
ꢀ
[N(3)eO(4) 1.210(4) A] and [N(3)eO(5) 1.222(4) A].
O
+
O
The corresponding bond lengths [C(14)eC(15) and C(15)eC(16)]
O
N
N
N
CH3
ꢀ
H3C
O
in molecule 17 (Fig. 6a) are shortening to 1.415(5) and 1.417(5) A,
N
H3C
respectively. This fact is due to sp2-hybridization of C5. The bond
H3C
+
O
8
13
21
ꢀ
ꢀ
lengths O(7)eK(1) [2.687(3) A], C(13)eO(7) [1.229(5) A] lie within
the range of normal covalent distances. Similar geometric pecu-
liarities of the nitro group are observed in molecule 18 (Fig. 6b)
[N(5)eO(5) 1.189(5) and N(5)eO(4) 1.195(5)]. The sp2-hybridization
of the C11-carbon was clear [C(12)eC(11)eN(5) 118.2(3)ꢁ]. The
bond lengths and angles of the imidazolium cation are close to
those reported in the literature.40
Interestingly, the CeO bond lengths assigned for the carbonyl
group located between two nitrogen atoms in compounds 13, 14, 17
and 18 reveal some important feature, for compounds 13 and 14
Cl
Cl
H3C
N
N
O
via:
N
O
N
CH3
H3C
O
O
22
N
H3C
O
O
O
O
N
N
O
N
H3C
O
O
Cl
N
N
H3C
H3C
CH3
O
ꢀ
these bonds have approximately the same lengths (w1.200 A),
Scheme 3. The proposed mechanism for 21.
while the corresponding bond lengths in 18 and 17 are 1.213 and

1008
E. Mallah et al. / Tetrahedron 68 (2012) 1005e1010
Fig. 5. View of compounds 13 (a) and 14 (b) in the crystal with atomic numbering
scheme.
ꢀ
1.229 A, respectively. This observation is attributed to the de-
localization of negative charge in pyridinium ring in 17 and 18; in
addition, it is worthy to note that this bond in compound 17 is
slightly longer due to the effect of strongly electron withdrawing
group (CN) in compound 18.
The five-membered ring in compound 21 is in an envelope
conformation, whereas one of the barbiturate rings is almost planar
while the others show much larger deviations from planarity
(Fig. 7). However, the bond distances and angles of the trimer are in
agreement with those observed in the previous reported data.36
3. Conclusion
In summary,
a
facile synthesis of
a
series of 1,3-
dimethylbarbituric acid derivatives in very good yields via nucleo-
philic substitution strategy is reported. Synthetic utility of the nu-
cleophilic attack of different nucleophiles onto 5,5-dichloro-1,3-
dimethyl-2,4,6(1H,3H,5H)-pyrimidinetrione (13) has been high-
lighted. The reactions demonstrated broad substrate scope and good
substitution tolerance. Furthermore, we have presented a new
procedure for the synthesis of 1,3-dimethylbarbituric acid trimer
(21) by employing the strongly nucleophilic character of N-hetero-
cyclic carbenes with a proposed mechanism. Compared to the well-
established protocol, it is noteworthy that this process is sufficiently
rapid, efficient and purification of the trimer involves simple crys-
tallisation from a suitable solvent. In view of extensive use of bar-
bituric acid derivatives in medicinal chemistry, the compounds
prepared in the present study and the methodology developed here
mayfinduseful applicationsin bio-organic andmedicinal chemistry.
Fig. 6. View of the ion pair of compounds 17 (a) and 18 (b) in the crystal with atomic
numbering scheme.
diisopropyl-4,5-dimethylimidazol-2-ylidene (8) was prepared as
described previously.41 NMR spectra-chemical shifts were recorded
with a Bruker DRX 250 NMR spectrometer and reported as
d values
(ppm) indirectly referenced to the solvent signal; J values are in hertz,
and splitting patterns are designated as follows: s (singlet), d (dou-
blet), sept (septet). The capital letter B, like in C2B, refers to the bar-
bituric acid ring system. Mass spectra were recorded on a Finnigan
Triple-Stage-Quadrupol spectrometer (TSQ-70) from Finnigan-Mat.
The used mass spectrometric ionization method was Fast-atom
bombardment (FAB) by 70 eV in a nitrobenzylalcohol matrix at
60 ꢁC. Elemental analyses were measured by elemental analyzers
from Carlo Erba Company, Model 1106 and HEKAtech GmbH.
4. Experimental section
4.1. General
4.2. Representative procedures for preparation of 13, 14, 17, 18
and 21
Commercially available reagents were purchased from Aldrich
and were used without further purification. All reactions were per-
formed in purified solvents under argon. 2,3-Dihydro-1,3-
4.2.1. 5,5-Dichloro-1,3-dimethyl-2,4,6(1H,3H,5H)-pyrimidinetrione
(13). A solution of sulfuryl chloride (1.45 mL, 18.0 mmol) and

E. Mallah et al. / Tetrahedron 68 (2012) 1005e1010
1009
then filtered off and dried in vacuo. The product was purified by
crystallisation from CH2Cl2/diethylether to give 18 (1.58 g, 86%) as
colourless crystals. dH (250 MHz, CDCl3) 3.06 (s, 6H, 1,3-MeB), 1.43
(d, J¼6.8 Hz, 12H, 1,3-CHMe2), 2.16 (s, 6H, 4,5-Me), 4.78 (sept, 2H,
CHMe2); dC (62.5 MHz, CDCl3) 30.6 (1,3-MeB), 151.6 (C2B), 114.2
(C5B), 158.2 (C4,6B), 9.8 (4,5-Me), 20.2 (1,3-CHMe2), 52.6 (1,3-
CHMe2), 126.3 (C4,5), 127.9 (C2). Anal. Calcd for C17H26ClN5O5: C
49.10, H 6.30, N 16.84. Found C 49.39, H 6.02, N 16.71. MS (FAB), m/z:
215 [100, Mþ], 173 [14, MþꢀC3H7], 136 [23, Mþꢀ(C3H7), ꢀCl] and
further fragments.
4.2.5. 5,6-Dihydro-1,3-dimethyl-5,6-bis-[10,30-dimethyl]-20,40,60-tri-
oxopyrimid (50,50) yl[2,3-d] uracil (21). A solution of 8 (0.53 g,
2.9 mmol) in diethylether (10 mL) was cooled to ꢀ78 ꢁC, then was
added to 13 (0.65 g, 2.9 mmol) in diethylether (25 mL). After that,
the reaction mixture was allowed to stir at room temperature
overnight, and then the precipitate was filtered off, washed with
CH2Cl2 and dried in vacuo. The product was purified by crystal-
lisation from CH2Cl2/diethylether to give 21 (1.11 g, 83%) as col-
ourless crystals. dH (250 MHz, DMSO-d6) 3.26e3.29e3.52 (s,s,s,
6,9,3H,1,3-MeB). Anal. Calcd for C18H19N6O9: C 46.76, H 3.92, N
18.18. Found C 46.91, H 3.60, N 18.52. MS (FAB), m/z: 215 [100, Mþ],
173 [18, MþꢀC3H7], 136 [20, Mþꢀ(C3H7), ꢀCl] and further
fragments.
Fig. 7. View of the trimer in 21 with atomic numbering scheme.
1,3-dimethylbarbituric acid (1a) (1.40 g, 9.0 mmol) in THF (25 mL)
was refluxed at 85 ꢁC for 6 h. After cooling to room temperature, the
solvent was removed in vacuo and the residue recrystallised from
CH2Cl2/diethylether to give dichloro compound 13 (1.72 g, 85%) as
colourless crystals. dH (250 MHz, CDCl3) 3.30 (s, 6H, 1,3-Me); dC
(62.5 MHz, CDCl3) 30.7 (1,3-Me), 149.1 (C2), 72.2 (C5), 161.7 (C4,6).
Anal. Calcd for C6H6Cl2N2O3: C 32.02, H 2.69, N 12.45. Found C
32.25, H 2.51, N 12.68. MS (FAB), m/z: 225 [93, Mþ], 191 [100,
MþꢀCl] and further fragments.
4.3. X-ray crystallographic data
Suitable crystals for crystallographic investigations of 13, 14, 17
and 18 were obtained by slow diffusion of ether into CH2Cl2 solu-
tion. A crystal of 21 was obtained by slow evaporation of a solution
of 15.0 mg of 21 in methanol (5 mL). X-ray measurements for
synthesized compounds were carried out on a glass fibre with
epoxy cement at room temperature. Preliminary examination and
data collection were performed with a Stoe CAD4 and IPDS 2 dif-
4.2.2. 5-Chloro-1,3-dimethyl-5-nitro-2,4,6(1H,3H,5H)-pyrimidine-
trione (14). To a solution of 13 (0.80 g, 3.6 mmol) in acetonitrile
(30 mL), silver nitrite was added (1.25 g, 8.1 mmol) in one portion at
room temperature. The reaction mixture was allowed to stir at
room temperature overnight. Thereafter, the solvent was evapo-
rated in vacuo and the residue dissolved in CH2Cl2 (15 mL) and
filtered off. The CH2Cl2 filtrate was evaporated under reduced
pressure whereby a powder residue was obtained. It was purified
by crystallisation from CH2Cl2/diethylether to afford 14 (0.62 g,
73%) as colourless crystals. dH (250 MHz, CDCl3) 3.34 (s, 6H,1,3-Me);
dC (62.5 MHz, CDCl3) 30.6 (1,3-Me), 149.2 (C2), 89.2 (C5), 159.1
(C4,6). Anal. Calcd for C6H6ClN3O5: C 30.59, H 2.57, N 17.84. Found C
30.78, H 2.43, N 17.62. MS (FAB), m/z: 189 [6, MþꢀNO2], 161 [100,
MþꢀNO2ꢀ2Me] and further fragments.
fractometer with graphite-monochromated Mo
K
a
radiation
ꢀ
ꢀ
(l¼0.71073 A) and Cu K
a radiation (l¼1.54184 A). The structures
were solved by direct methods and refined by full-matrix least-
squares on F2 using SHELXS-9742 and SHELXTL V5.1 (NT). Details for
the structure solutions and refinements are given in Table 1 (Sup-
plementary data).
Acknowledgements
Financial support by the Deutsche Forschungsgemeinschaft and
the Higher Council for Science and Technology of Jordan is grate-
€
€
fully acknowledged. We also thank Dr. Cacilia Maichle-Moßmer for
her help with the X-ray measurements.
4.2.3. Potassium 5-cyano-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-
4-pyrimidinolate 1,4,7,10,13,16-hexaoxacyclooctadecane (17). To
a mixture of potassium cyanide (0.35 g, 5.4 mmol) and 18-crown-6
(0.93 g, 3.5 mmol) in CH2Cl2 (15 mL), a solution of 13 (0.40 g,
1.8 mmol) in CH2Cl2 (15 mL) was added. After being stirred at room
temperature overnight, the reaction mixture was concentrated in
vacuo. The resulting residue was recrystallised from CH2Cl2/dieth-
ylether to give 17 (0.48 g, 55%) as yellow crystals. dH (250 MHz,
CDCl3) 3.51 (s, 6H, 1,3-MeB), 3.65 (s, 12H, crown ether); dC
(62.5 MHz, CDCl3) 30.6 (1,3-MeB), 41.4 (C5B), 109.4 (CN), 154.3
(C2B), 165.1 (C4,6B). Anal. Calcd for C19H30N3O9K: C 47.19, H 6.25, N
8.69. Found C 47.43, H 6.24, N 8.98. MS (FAB), m/z: 180 [100, Mþ]
and further fragments.
Supplementary data
Supplementary crystallographic data associated with this article
(CCDC 842202, CCDC 842203, CCDC 842204, CCDC 842205 and
CCDC 842380) can be found free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_-
request/cif. In addition, crystal data and structure refinement for
C6H6Cl2N2O3 (13), C6H6ClN3O5 (14), C19H30N3O9K (17),
C17H26ClN5O5 (18), and C18H19N6O9 (21) are contained in the Sup-
plementary data. Supplementary data related to this article can be
found online at doi:10.1016/j.tet.2011.11.093.
4.2.4. 2-Chloro-1,3-diisopropyl-4,5-dimethyl-1H-imidazol-3-ium
1,3-dimethyl-5-nitro-2,6-dioxo-1,2,3,6-tetrahydro-4-pyrimidinolate
(18). A solution of 8 (0.80 g, 4.4 mmol) in diethylether (10 mL) was
cooled to ꢀ78 ꢁC, then added to a solution of 14 (1.04 g 4.4 mmol)
in diethylether (25 mL). Thereafter, the reaction mixture was
allowed to stir at room temperature overnight. The precipitate was
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