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

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270107023475/fa3076sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270107023475/fa3076Isup2.hkl
Contains datablock I

CCDC reference: 655506

Comment top

N-Methyl-D-aspartate receptors (NMDARs) are highly regulated ligand-gated ionotropic glutamate receptor channels, that are affected by many substrates, including the endogenous ligand, glycine. The cation channel is nonselectively permeable to Na+, K+ and Ca2+, but is blocked by Mg2+ at physiological 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 flux.

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 aminoguanidine hydrochloride, and exhibited potent inhibition of the NMDAR complex in the presence of spermidine.

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.

The values for the bond lengths in the guanidine group are comparable to those found in the starting material, aminoguanidine hydrochloride. The bond lengths reported for aminoguanidine are 1.32 Å for the two terminal exo C—N bonds of the guanidino group and 1.35 Å for the endo C—N bond of the guanidino group, which were calculated to correspond to a weighting of roughly 40% double-bond character for each of the exo C—N bonds and 20% double-bond character for the endo C—N bond. The bond lengths observed in the X-ray structure of compound (I) for the exo C10—N11 [1.324 (2) Å] and C10—N12 [1.317 (2) Å] bonds, and the endo C10—N9 [1.350 (2) Å] bond were in close accordance with the corresponding bond lengths in the aminoguanidine molecule. Thus the double-bond of the guanidine 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 structure, the chloride counter-ion is more closely associated with N12, which may account for the slightly shorter length of this terminal C10—N12 bond compared with the length of C10—N11.

Formation of the Schiff base at the C7—N8 bond also affects the length of the N8—N9 bond in (I). This corresponding N—N bond length in the aminoguanidine starting material was reported as 1.42 Å, but in (I), this bond was observed to have a length of 1.381 (2) Å, indicating slight double-bond character. The C1—C7 bond [1.459 (2) Å] is also shorter than a standard C—C σ bond, and it is clear that some double-bond character is distributed to some extent along the C1—C7—N8—N9—C10 bonds. The bond angles along this series of atoms (C1—C7—N8, C7—N8—N9 and N8—N9—C10; Table 1) are closer to the ideal value of 120° for angles between sp2 atoms than for the 109.5° value observed for sp3 atoms.

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 10° 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 C6—C1—C7—N8—N9—C10 chain of atoms, the torsion angles are a tight 176.38 (16), 178.78 (14) and 176.16 (15)° for C6—C1—C7—N8, C1—C7—N8—N9 and C7—N8—N9—C10, respectively. Planarity of the molecule also extends through O16 to C17, and thus includes the 4-methoxy group, as indicated by the bond angle of 117.53 (13)° formed along C4—O16—C17. The partial double-bond character of the C4—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 phenyl ring (C3). With the extended conjugation throughout the molecule, and the E geometry of the C7—N8 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.

The crystal packing for (I) is illustrated in Fig. 2, viewed along the b direction. The flat molecules form parallel stacks along the b axis, as do the chloride ions. Each chloride ion forms five hydrogen bonds with each of the five guanidine H atoms, with H···A lengths of 2.44–2.70 Å (see Table 2). This arrangement forms stable chains of intermolecular connectivity in the c direction.

Related literature top

For related literature, see: Dodd (2002); Gibson et al. (2002); Li et al. (2003); Lovinger et al. (1989); Meldrum et al. (1999).

Experimental top

4-Methoxy-3-nitrobenzaldehyde (287 mg, 1.6 mmol) and aminoguanidine hydrochloride (110 mg, 1.0 mmol) were dissolved in a minimal amount of methanol (15 ml) and the solution was then heated to reflux and stirred for a period of 12 h with TLC monitoring until the aminoguanidine hydrochloride was consumed. The resulting solution was evaporated on a rotary evaporator, and the yellow residue was stirred in chloroform 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 final filtered product was dried in vacuo overnight to afford a yellow powder (191 mg, 0.70 mmol, 70% yield, m.p. 517–520 K). Pale-yellow needle-like crystals of the product were obtained by recrystallization of the crude product from methanol. m/z (ES+ MS) = 238 (M+). 1H NMR (400 MHz, DMSO-d6): δ 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: δ 155.5, 152.8, 144.3, 139.8, 133.5, 126.3, 123.0, 114.4, 57.0.

Refinement top

The flat NH2 groups were allowed to refine along the N—H vector to distances of 0.856 (17) and 0.813 (18) Å. H atoms were found in difference Fourier maps and subsequently placed in idealized positions with constrained C—H distances of 0.95 (CAr—H) and 0.98 Å (CMe—H), and N—H 0.88 Å. Uiso(H) values were set to either 1.5Ueq or 1.2Ueq of the attached atom.

Computing details top

Data collection: COLLECT (Nonius, 1999); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO–SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP in SHELXTL (Sheldrick, 1995); software used to prepare material for publication: SHELX97-2 (Sheldrick, 1997) and local procedures.

Figures top
[Figure 1] Fig. 1. A view of the planar compound (I). Displacement ellipsoids are drawn at the 50% probability level, with H atoms included as small spheres of arbitrary radii.
[Figure 2] Fig. 2. The stacking arangement in the crystal structure of the title compound, viewed along the b axis.
(4-Methoxy-3-nitrobenzylideneamino)guanidinium chloride top
Crystal data top
C9H12N5O3+·ClF(000) = 568
Mr = 273.69Dx = 1.513 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 3023 reflections
a = 16.7260 (4) Åθ = 1.0–27.5°
b = 5.1384 (1) ŵ = 0.33 mm1
c = 14.0045 (5) ÅT = 90 K
β = 93.1793 (13)°Irregular block, yellow
V = 1201.76 (6) Å30.25 × 0.16 × 0.08 mm
Z = 4
Data collection top
Nonius KappaCCD
diffractometer
2744 independent reflections
Radiation source: fine-focus sealed tube2220 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.024
Detector resolution: 18 pixels mm-1θmax = 27.5°, θmin = 1.2°
ω scans at fixed χ = 55°h = 2121
Absorption correction: multi-scan
(SCALEPACK; Otwinowski & Minor, 1997)
k = 66
Tmin = 0.923, Tmax = 0.976l = 1718
4859 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.041Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.111H atoms treated by a mixture of independent and constrained refinement
S = 1.07 w = 1/[σ2(Fo2) + (0.0574P)2 + 0.6173P]
where P = (Fo2 + 2Fc2)/3
2744 reflections(Δ/σ)max = 0.001
166 parametersΔρmax = 0.35 e Å3
0 restraintsΔρmin = 0.44 e Å3
Crystal data top
C9H12N5O3+·ClV = 1201.76 (6) Å3
Mr = 273.69Z = 4
Monoclinic, P21/cMo Kα radiation
a = 16.7260 (4) ŵ = 0.33 mm1
b = 5.1384 (1) ÅT = 90 K
c = 14.0045 (5) Å0.25 × 0.16 × 0.08 mm
β = 93.1793 (13)°
Data collection top
Nonius KappaCCD
diffractometer
2744 independent reflections
Absorption correction: multi-scan
(SCALEPACK; Otwinowski & Minor, 1997)
2220 reflections with I > 2σ(I)
Tmin = 0.923, Tmax = 0.976Rint = 0.024
4859 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0410 restraints
wR(F2) = 0.111H atoms treated by a mixture of independent and constrained refinement
S = 1.07Δρmax = 0.35 e Å3
2744 reflectionsΔρmin = 0.44 e Å3
166 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Cl10.59641 (3)0.07437 (9)1.11857 (3)0.02220 (14)
C10.76199 (10)0.2368 (3)0.83533 (12)0.0173 (3)
C20.77609 (10)0.2913 (4)0.93282 (12)0.0186 (4)
H20.74860.19810.97960.022*
C30.83035 (10)0.4821 (4)0.95963 (11)0.0193 (4)
C40.87253 (10)0.6281 (3)0.89483 (12)0.0189 (4)
C50.85614 (10)0.5785 (4)0.79767 (12)0.0197 (4)
H50.88250.67560.75100.024*
C60.80136 (10)0.3871 (4)0.76958 (12)0.0195 (4)
H60.79030.35730.70320.023*
C70.70580 (10)0.0348 (4)0.80221 (12)0.0183 (4)
H70.69380.01260.73560.022*
N80.67259 (8)0.1127 (3)0.86196 (10)0.0180 (3)
N90.61946 (8)0.2926 (3)0.82169 (10)0.0185 (3)
H90.60800.29450.75960.022*
C100.58556 (10)0.4654 (4)0.87971 (12)0.0186 (4)
N110.54255 (9)0.6545 (3)0.83821 (11)0.0224 (3)
H11A0.5191 (4)0.7661 (19)0.8725 (6)0.027*
H11B0.53819 (12)0.6653 (4)0.7771 (10)0.027*
N120.59436 (9)0.4392 (3)0.97324 (10)0.0205 (3)
H12A0.5729 (4)0.5416 (19)1.0080 (7)0.025*
H12B0.6212 (5)0.321 (2)0.9963 (4)0.025*
N130.84128 (9)0.5450 (3)1.06182 (10)0.0219 (3)
O140.78203 (9)0.6130 (4)1.10253 (10)0.0408 (4)
O150.90798 (8)0.5240 (3)1.10144 (9)0.0323 (3)
O160.92256 (7)0.8137 (3)0.93170 (9)0.0231 (3)
C170.96690 (11)0.9628 (4)0.86592 (13)0.0258 (4)
H17A1.00020.84580.82970.039*
H17B1.00121.08830.90150.039*
H17C0.92961.05620.82170.039*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0288 (2)0.0232 (2)0.0145 (2)0.00187 (18)0.00039 (16)0.00218 (17)
C10.0180 (8)0.0190 (9)0.0150 (8)0.0020 (7)0.0010 (6)0.0006 (7)
C20.0195 (8)0.0210 (9)0.0155 (8)0.0007 (7)0.0019 (6)0.0028 (7)
C30.0230 (9)0.0228 (9)0.0122 (8)0.0034 (7)0.0004 (7)0.0010 (7)
C40.0184 (8)0.0190 (9)0.0193 (8)0.0008 (7)0.0006 (7)0.0001 (7)
C50.0212 (8)0.0224 (9)0.0157 (8)0.0016 (7)0.0032 (7)0.0032 (7)
C60.0219 (8)0.0234 (9)0.0131 (7)0.0032 (7)0.0012 (6)0.0002 (7)
C70.0199 (8)0.0224 (9)0.0126 (8)0.0022 (7)0.0003 (6)0.0003 (7)
N80.0180 (7)0.0213 (8)0.0145 (7)0.0000 (6)0.0005 (5)0.0014 (6)
N90.0215 (7)0.0220 (8)0.0116 (6)0.0031 (6)0.0016 (5)0.0005 (6)
C100.0167 (8)0.0213 (9)0.0177 (8)0.0019 (7)0.0008 (6)0.0008 (7)
N110.0261 (8)0.0232 (8)0.0179 (7)0.0031 (6)0.0017 (6)0.0003 (6)
N120.0249 (8)0.0225 (8)0.0143 (7)0.0039 (6)0.0020 (6)0.0015 (6)
N130.0265 (8)0.0243 (8)0.0147 (7)0.0034 (6)0.0003 (6)0.0006 (6)
O140.0352 (8)0.0666 (12)0.0214 (7)0.0008 (8)0.0083 (6)0.0131 (7)
O150.0329 (8)0.0430 (9)0.0201 (7)0.0003 (7)0.0074 (6)0.0012 (6)
O160.0262 (6)0.0241 (7)0.0190 (6)0.0059 (5)0.0006 (5)0.0004 (5)
C170.0252 (9)0.0277 (10)0.0244 (9)0.0064 (8)0.0002 (7)0.0049 (8)
Geometric parameters (Å, º) top
C1—C61.395 (2)N9—C101.350 (2)
C1—C21.401 (2)N9—H90.8800
C1—C71.459 (2)C10—N121.317 (2)
C2—C31.374 (3)C10—N111.324 (2)
C2—H20.9500N11—H11A0.856 (17)
C3—C41.398 (2)N11—H11B0.856 (17)
C3—N131.469 (2)N12—H12A0.813 (18)
C4—O161.352 (2)N12—H12B0.813 (18)
C4—C51.396 (2)N13—O141.221 (2)
C5—C61.386 (3)N13—O151.223 (2)
C5—H50.9500O16—C171.436 (2)
C6—H60.9500C17—H17A0.9800
C7—N81.279 (2)C17—H17B0.9800
C7—H70.9500C17—H17C0.9800
N8—N91.381 (2)
C6—C1—C2118.21 (16)C10—N9—N8118.48 (14)
C6—C1—C7120.24 (15)C10—N9—H9120.8
C2—C1—C7121.52 (15)N8—N9—H9120.8
C3—C2—C1118.81 (16)N12—C10—N11122.66 (16)
C3—C2—H2120.6N12—C10—N9120.27 (16)
C1—C2—H2120.6N11—C10—N9117.05 (15)
C2—C3—C4123.70 (15)C10—N11—H11A120.0 (6)
C2—C3—N13117.91 (15)C10—N11—H11B120.0 (2)
C4—C3—N13118.30 (16)H11A—N11—H11B120.0 (6)
O16—C4—C5125.77 (16)C10—N12—H12A120.0 (7)
O16—C4—C3117.04 (15)C10—N12—H12B120.0 (5)
C5—C4—C3117.10 (16)H12A—N12—H12B119.9 (8)
C6—C5—C4119.79 (16)O14—N13—O15123.85 (15)
C6—C5—H5120.1O14—N13—C3117.22 (14)
C4—C5—H5120.1O15—N13—C3118.92 (15)
C5—C6—C1122.30 (15)C4—O16—C17117.53 (13)
C5—C6—H6118.9O16—C17—H17A109.5
C1—C6—H6118.9O16—C17—H17B109.5
N8—C7—C1120.63 (15)H17A—C17—H17B109.5
N8—C7—H7119.7O16—C17—H17C109.5
C1—C7—H7119.7H17A—C17—H17C109.5
C7—N8—N9115.00 (14)H17B—C17—H17C109.5
C6—C1—C2—C32.7 (3)C6—C1—C7—N8176.38 (16)
C7—C1—C2—C3179.31 (16)C2—C1—C7—N85.7 (3)
C1—C2—C3—C40.4 (3)C1—C7—N8—N9178.78 (14)
C1—C2—C3—N13177.02 (15)C7—N8—N9—C10176.16 (15)
C2—C3—C4—O16178.42 (16)N8—N9—C10—N129.3 (2)
N13—C3—C4—O161.8 (2)N8—N9—C10—N11172.09 (14)
C2—C3—C4—C51.7 (3)C2—C3—N13—O1457.4 (2)
N13—C3—C4—C5174.92 (15)C4—C3—N13—O14119.4 (2)
O16—C4—C5—C6177.85 (16)C2—C3—N13—O15121.72 (19)
C3—C4—C5—C61.4 (3)C4—C3—N13—O1561.5 (2)
C4—C5—C6—C10.9 (3)C5—C4—O16—C174.3 (3)
C2—C1—C6—C53.0 (3)C3—C4—O16—C17179.29 (16)
C7—C1—C6—C5178.99 (16)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N9—H9···Cl1i0.882.443.1961 (14)144
N11—H11A···Cl1ii0.857 (9)2.507 (8)3.2524 (16)146.0
N11—H11B···Cl1i0.857 (14)2.517 (12)3.2787 (16)148.6
N12—H12A···Cl1iii0.814 (9)2.526 (10)3.2223 (16)144.4
N12—H12B···Cl10.812 (9)2.704 (9)3.3315 (16)135.5 (7)
Symmetry codes: (i) x, y1/2, z1/2; (ii) x+1, y1, z+2; (iii) x, y1, z.

Experimental details

Crystal data
Chemical formulaC9H12N5O3+·Cl
Mr273.69
Crystal system, space groupMonoclinic, P21/c
Temperature (K)90
a, b, c (Å)16.7260 (4), 5.1384 (1), 14.0045 (5)
β (°) 93.1793 (13)
V3)1201.76 (6)
Z4
Radiation typeMo Kα
µ (mm1)0.33
Crystal size (mm)0.25 × 0.16 × 0.08
Data collection
DiffractometerNonius KappaCCD
diffractometer
Absorption correctionMulti-scan
(SCALEPACK; Otwinowski & Minor, 1997)
Tmin, Tmax0.923, 0.976
No. of measured, independent and
observed [I > 2σ(I)] reflections
4859, 2744, 2220
Rint0.024
(sin θ/λ)max1)0.649
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.041, 0.111, 1.07
No. of reflections2744
No. of parameters166
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.35, 0.44

Computer programs: COLLECT (Nonius, 1999), SCALEPACK (Otwinowski & Minor, 1997), DENZO–SMN (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), XP in SHELXTL (Sheldrick, 1995), SHELX97-2 (Sheldrick, 1997) and local procedures.

Selected geometric parameters (Å, º) top
C1—C71.459 (2)N9—C101.350 (2)
C3—N131.469 (2)C10—N121.317 (2)
C4—O161.352 (2)C10—N111.324 (2)
C7—N81.279 (2)N13—O141.221 (2)
N8—N91.381 (2)O16—C171.436 (2)
C2—C1—C7121.52 (15)N8—C7—C1120.63 (15)
C4—C3—N13118.30 (16)C7—N8—N9115.00 (14)
O16—C4—C5125.77 (16)C10—N9—N8118.48 (14)
O16—C4—C3117.04 (15)N11—C10—N9117.05 (15)
C2—C1—C7—N85.7 (3)C2—C3—N13—O1457.4 (2)
N8—N9—C10—N129.3 (2)C4—C3—N13—O1561.5 (2)
N8—N9—C10—N11172.09 (14)C3—C4—O16—C17179.29 (16)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N9—H9···Cl1i0.882.443.1961 (14)144.0
N11—H11A···Cl1ii0.857 (9)2.507 (8)3.2524 (16)146.0
N11—H11B···Cl1i0.857 (14)2.517 (12)3.2787 (16)148.6
N12—H12A···Cl1iii0.814 (9)2.526 (10)3.2223 (16)144.4
N12—H12B···Cl10.812 (9)2.704 (9)3.3315 (16)135.5 (7)
Symmetry codes: (i) x, y1/2, z1/2; (ii) x+1, y1, z+2; (iii) x, y1, z.
 

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