(4-Meth-oxy-3-nitro-benzyl-idene-amino)-guanidinium chloride

Article abstract of DOI:10.1107/S0108270107023475

In the title compound, C9H12N5O3 ⁺·Cl^-, the cation is almost entirely planar. The imine double bond is exclusively in the E geometry. International Union of Crystallography 2007.

Full text of DOI:10.1107/S0108270107023475

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
In order to establish the structure and geometry of
compound (I), suitable crystals of this compound were
prepared for X-ray analysis. The data obtained demonstrated
an exclusive E geometry in the newly formed imine double
bond. An ellipsoid plot of the product is provided in Fig. 1, and
selected geometric parameters are included in Table 1.
ISSN 0108-2701
(4-Methoxy-3-nitrobenzylidene-
amino)guanidinium chloride
Joshua R. Ring,a Sean Parkinb and Peter A. Crooksa*
aDepartment of Pharmaceutical Sciences, College of Pharmacy, University of
Kentucky, Lexington, KY 40536, USA, and bDepartment of Chemistry, University of
Kentucky, Lexington, KY 40506, USA
The values for the bond lengths in the guanidine group are
comparable to those found in the starting material amino-
guanidine hydrochloride. The bond lengths reported for
Correspondence e-mail: pcrooks@uky.edu
Ê
aminoguanidine are 1.32 A for the two terminal exo CÐN
Ê
bonds of the guanidino group and 1.35 A for the endo CÐN
Received 5 February 2007
Accepted 13 May 2007
Online 14 June 2007
bond of the guanidino group, which were calculated to
correspond to a weighting of roughly 40% double-bond
character for each of the exo CÐN bonds and 20% double-
bond character for the endo CÐN bond. The bond lengths
observed in the X-ray structure of compound (I) for the exo
+
In the title compound, C9H12N5O3 ÁCl , the cation is almost
entirely planar. The imine double bond is exclusively in the E
geometry.
Ê
Ê
C10ÐN11 [1.324 (2) A] and C10ÐN12 [1.317 (2) A] bonds,
Ê
and the endo C10ÐN9 [1.350 (2) A] bond, were in close
accordance with the corresponding bond lengths in the
aminoguanidine molecule. Thus, the double bond of the
guanidinium group in (I) is predominantly exo, as is observed
in the aminoguanidine structure, in spite of the presence of a
new arylimine grouping in the molecule. In the crystal struc-
ture, the chloride counter-ion is more closely associated with
N12, which may account for the slightly shorter length of this
terminal C10ÐN12 bond compared with the length of C10Ð
N11.
Comment
N-Methyl-d-aspartate receptors (NMDARs) are highly regu-
lated ligand-gated ionotropic glutamate receptor channels that
are affected by many substrates, including the endogenous
ligand, glycine. The cation channel is nonselectively perme-
able to Na+, K+ and Ca2+, but is blocked by Mg2+ at physio-
logical conditions. Overactivation of the NMDAR can lead to
hyperexcitablility and a number of neurotoxic effects and
neurological diseases, such as epilepsy (Meldrum et al., 1999),
Alzheimer's disease (Dodd, 2002) and Huntington's disease
(Li et al., 2003), and has also been shown to be a mechanism
that leads to alcohol dependence (Lovinger et al., 1989).
However, the physiological function of this channel is crucial
in many neural functions, such as learning and memory, and
thus a therapeutic agent that is an antagonist at NMDARs
cannot be one which irreversibly inhibits channel ¯ux.
Formation of the Schiff base at the C7ÐN8 bond also
affects the length of the N8ÐN9 bond in (I). This corre-
sponding NÐN bond length in the aminoguanidine starting
Ê
material was reported as 1.42 A, but in (I), this bond was
Ê
observed to have a length of 1.381 (2) A, indicating slight
Ê
double-bond character. The C1ÐC7 bond [1.459 (2) A] is also
shorter than a standard CÐC ꢀ bond, and it is clear that some
The polyamine agmatine has been demonstrated to exhibit
antagonist activity at the polyamine binding sites of NR2B
subunits of the NMDAR complex, but only in the presence of
pathologically high levels of the longer-chain polyamine-site
agonists, such as spermine and spermidine (Gibson et al.,
2002). The intriguing properties of agmatine as a potent and
selective allosteric competitive inhibitor of the NMDAR
complex have led to an interest in optimizing the structure of
this molecule for use in drug development. As a result,
conjugates of aminoguanidine and an array of arylaldehydes
have been synthesized and screened as NMDAR inhibitors.
Thus, the title compound, (I), was synthesized from Schiff base
formation of 4-methoxy-3-nitrobenzaldehyde with amino-
guanidine hydrochloride, and exhibited potent inhibition of
the NMDAR complex in the presence of spermidine.
Figure 1
A view of the planar compound (I). Displacement ellipsoids are drawn at
the 50% probability level and H atoms are included as small spheres of
arbitrary radii.
o392 # 2007 International Union of Crystallography
DOI: 10.1107/S0108270107023475
Acta Cryst. (2007). C63, o392±o394

organic compounds
double-bond character is distributed to some extent along the
C1ÐC7ÐN8ÐN9ÐC10 bond series. The bond angles along
this series of atoms (C1ÐC7ÐN8, C7ÐN8ÐN9 and N8Ð
N9ÐC10; Table 1) are closer to the ideal value of 120ꢀ for
angles between sp2 atoms than to the value of 109.5ꢀ observed
for sp3 atoms.
Experimental
4-Methoxy-3-nitrobenzaldehyde (287 mg, 1.6 mmol) and amino-
guanidine hydrochloride (110 mg, 1.0 mmol) were dissolved in a
minimal amount of methanol (15 ml), and the solution was then
heated to re¯ux and stirred for a period of 12 h with monitoring by
thin-layer chromatography until the aminoguanidine hydrochloride
was consumed. The resulting solution was evaporated on a rotary
evaporator, and the yellow residue obtained was stirred in chloro-
form for 30 min in order to dissolve the remaining aldehyde starting
material. The solid product was stirred in chloroform and the above
process repeated. The ®nal ®ltered product was dried in vacuo
overnight to afford a yellow powder (yield 191 mg, 0.70 mmol, 70%;
m.p. 517±520 K). Pale-yellow needle-like crystals of the product were
obtained by recrystallization of the crude product from methanol.
The assumption of an extended double-bond characteristic
throughout the molecule is also supported by the planarity of
the entire molecule, as is seen in the torsion angle values
(Table 1). None of the torsion angles deviate by more than 10ꢀ
from the plane of the molecule, except for the O atoms of the
nitro group and the H atoms of the methyl group. Along the
C6ÐC1ÐC7ÐN8ÐN9ÐC10 chain of atoms, the torsion
angles are a tight 176.38 (16), 178.78 (14) and 176.16 (15)ꢀ for
C6ÐC1ÐC7ÐN8, C1ÐC7ÐN8ÐN9 and C7ÐN8ÐN9Ð
C10, respectively. Planarity of the molecule also extends
through atoms O16 to C17, and thus includes the 4-methoxy
group, as indicated by the C4ÐO16ÐC17 bond angle of
117.53 (13)ꢀ. The partial double-bond character of the C4Ð
O16 bond results in C3 and C17 possessing an E geometry,
which is probably a result of the steric hindrance of the nitro
substituent at position 3 of the benzene ring (C3). With the
extended conjugation throughout the molecule, and the E
geometry of the C7ÐN8 bond, there is no possibility of
intramolecular hydrogen-bond formation between the O
atoms of the nitro group and the H atoms attached to N atoms
of the guanidine group.
m/z (ES+ MS) = 238 (M+). H NMR (400 MHz, DMSO-d6): ꢁ 12.23
(1H, s), 8.47 (1H, d, J = 2.0 Hz), 8.18 (1H, s), 8.11 (1H, dd, J = 4.8 and
2.0 Hz), 7.42 (1H, d, J = 4.8 Hz), 3.97 (3H, s); 13C NMR: ꢁ 155.5, 152.8,
144.3, 139.8, 133.5, 126.3, 123.0, 114.4, 57.0.
1
Crystal data
+
3
Ê
V = 1201.76 (6) A
C9H12N5O3 ÁCl
Mr = 273.69
Monoclinic, P21=c
Z = 4
Mo Kꢃ radiation
1
Ê
a = 16.7260 (4) A
ꢄ = 0.33 mm
T = 90.0 (2) K
Ê
b = 5.1384 (1) A
Ê
c = 14.0045 (5) A
0.25 Â 0.16 Â 0.08 mm
ꢂ = 93.1793 (13)ꢀ
Data collection
Nonius KappaCCD diffractometer
Absorption correction: multi-scan
(SCALEPACK; Otwinowski &
Minor, 1997)
4859 measured re¯ections
2744 independent re¯ections
2220 re¯ections with I > 2ꢀ(I)
Rint = 0.024
The crystal packing for (I) is illustrated in Fig. 2, viewed
along the b direction. The ¯at molecules form parallel stacks
along the b axis, as do the chloride ions. Each chloride ion
forms ®ve hydrogen bonds with each of the ®ve guanidine H
Tmin = 0.923, Tmax = 0.976
Re®nement
R[F2 > 2ꢀ(F2)] = 0.041
wR(F2) = 0.111
S = 1.07
2744 re¯ections
166 parameters
H atoms treated by a mixture of
independent and constrained
re®nement
Ê
atoms, with HÁ Á ÁA distances in the range 2.44±2.70 A (see
Table 2). This arrangement forms stable chains of inter-
molecular connectivity in the c direction.
3
Ê
Áꢅmax = 0.35 e A
3
Ê
0.44 e A
Áꢅmin
=
Table 1
Selected geometric parameters (A, ).
ꢀ
Ê
C1ÐC7
C3ÐN13
C4ÐO16
C7ÐN8
N8ÐN9
1.459 (2)
1.469 (2)
1.352 (2)
1.279 (2)
1.381 (2)
N9ÐC10
1.350 (2)
1.317 (2)
1.324 (2)
1.221 (2)
1.436 (2)
C10ÐN12
C10ÐN11
N13ÐO14
O16ÐC17
C2ÐC1ÐC7
C4ÐC3ÐN13
O16ÐC4ÐC5
O16ÐC4ÐC3
121.52 (15)
118.30 (16)
125.77 (16)
117.04 (15)
N8ÐC7ÐC1
C7ÐN8ÐN9
C10ÐN9ÐN8
N11ÐC10ÐN9
120.63 (15)
115.00 (14)
118.48 (14)
117.05 (15)
C2ÐC1ÐC7ÐN8
N8ÐN9ÐC10ÐN12
N8ÐN9ÐC10ÐN11
5.7 (3)
9.3 (2)
172.09 (14)
C2ÐC3ÐN13ÐO14
C4ÐC3ÐN13ÐO15
C3ÐC4ÐO16ÐC17
57.4 (2)
61.5 (2)
179.29 (16)
The ¯at NH2 groups were allowed to re®ne along the NÐH vector
Ê
to distances of 0.856 (17) and 0.813 (18) A. H atoms were found in
difference Fourier maps and subsequently placed in idealized posi-
Ê
tions with constrained CÐH distances of 0.95 (aromatic) and 0.98 A
Ê
(methyl), and an NÐH distance of 0.88 A. Uiso(H) values were set at
either 1.5Ueq or 1.2Ueq of the attached atom.
Figure 2
The stacking arrangement in the crystal structure of the title compound,
viewed along the b axis.
+
ꢁ
Acta Cryst. (2007). C63, o392±o394
Ring et al.
C9H12N5O3 ÁCl
o393

organic compounds
Table 2
Hydrogen-bond geometry (A, ).
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: FA3076). Services for accessing these data are
described at the back of the journal.
ꢀ
Ê
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
N9ÐH9Á Á ÁCl1i
0.88
0.86
0.86
0.81
0.81
2.44
2.51
2.52
2.53
2.70
3.1961 (14)
3.2524 (16)
3.2787 (16)
3.2223 (16)
3.3315 (16)
144
146
149
144
136
N11ÐH11AÁ Á ÁCl1ii
N11ÐH11BÁ Á ÁCl1i
N12ÐH12AÁ Á ÁCl1iii
N12ÐH12BÁ Á ÁCl1
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È
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+
ꢁ
o394 Ring et al. C9H12N5O3 ÁCl
Acta Cryst. (2007). C63, o392±o394