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Acta Crystallogr Sect E Struct Rep Online. 2010 June 1; 66(Pt 6): o1486.
Published online 2010 May 29. doi:  10.1107/S1600536810019495
PMCID: PMC2979596

5-Methyl-3,6,7,8a-tetra­hydro-2H-diimidazo[1,2-c:1′,2′-e]pyrido[1,2-a][1,3,5]triazin-5-ium iodide

Abstract

The structure of the title compound, C12H16N5 +·I, shows that the methyl­ation reaction with CH3I occurred at the imine N atom at position 5 of the 3,6,7,8a-tetra­hydro-2H-diimidazo[1,2-c:1′,2′-e]pyrido[1,2-a][1,3,5]triazine system. In the cation, the sp 3-hybridized C atom belonging to the fused dihydro­pyrine and dihydro-1,3,5-triazine rings deviates by 0.514 (3) Å from the best plane defined by the remaining cationic non-H atoms. The fused dihydro­pyridine and dihydro-1,3,5-triazine rings are each in a half-chair conformation with the sp 3-hybridized C atom as a flap. The iodide anion is 3.573 (2) Å from the methyl­ated N atom and exhibits five short C—H(...)I contacts with distances less than 3.16 Å. The structure has been determined from a non-merohedral twin with twin law [−1 0 0 0 − 1 0 0.115 0 1], minor domain = 0.1559 (12).

Related literature

For the synthesis and data reported earlier for the title compound, see: Sączewski & Foks (1981 [triangle]). For the programs used to derive the twin law, see: Cooper et al.(2002 [triangle]); Farrugia (1999 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o1486-scheme1.jpg

Experimental

Crystal data

  • C12H16N5 +·I
  • M r = 357.20
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o1486-efi1.jpg
  • a = 7.6299 (2) Å
  • b = 15.3939 (4) Å
  • c = 11.4503 (3) Å
  • β = 92.204 (2)°
  • V = 1343.89 (6) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 2.37 mm−1
  • T = 100 K
  • 0.2 × 0.2 × 0.1 mm

Data collection

  • Oxford Diffraction Xcalibur-E CCD diffractometer
  • Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009 [triangle]) T min = 0.496, T max = 0.789
  • 25955 measured reflections
  • 4406 independent reflections
  • 4018 reflections with I > 2σ(I)
  • R int = 0.026

Refinement

  • R[F 2 > 2σ(F 2)] = 0.029
  • wR(F 2) = 0.070
  • S = 1.20
  • 4406 reflections
  • 165 parameters
  • H-atom parameters constrained
  • Δρmax = 1.74 e Å−3
  • Δρmin = −1.24 e Å−3

Data collection: CrysAlis PRO (Oxford Diffraction, 2009 [triangle]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]) and WinGX (Farrugia, 1999 [triangle]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810019495/tk2676sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810019495/tk2676Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

supplementary crystallographic information

Comment

Biguanide derivatives are known to possess diverse biological activities, including antidiabetic, antibacterial, germicidic, antiviral and antimalarial. On the other hand, quaternary ammonium salts constitute a well known class of bacteriostatic agents. Therefore, we have decided to synthesize some N-alkylated cyclic biguanide derivatives for biological testing, based on the previously described procedure (Sączewski & Foks, 1981) which consists in the reaction of 2,3,6,7,8a,13-hexahydropyrido[1,2-a]diimidazo[1',2'-c:1'',2''-e]-1,3,5-triazine (1) with an alkyl halide. As shown in Fig. 1, the course of the reaction of 1 with methyl iodide has not been established and two products, 2 or 3, arising from either N1 or N5 alkylation have been proposed. In this work, based on X-ray structure analysis (Fig. 2) and hetero-correlation NMR experiments (HSQC and HMBC), the structure of the title compound (2) is determined unambiguously. Regioselectivity of N-alkylation of the cyclic biguanide derivative 1 could not be predicted on the basis of calculated electrostatic potential and charge distribution. The structure of the N5 alkylated product 2 was also confirmed by 2D NMR spectroscopic data. Thus, assignment of signals observed in 1H and 13C-NMR spectra was possible using HSQC spectrum (see numbering scheme in Fig. 3). The crucial signals of quaternary carbon atoms C13a and C4a were found at 145.7 and 152.6 p.p.m., respectively. 3-Bond correlation from the latter carbon to a singlet of three protons at 3.26 p.p.m. observed in the HMBC spectrum (Fig. 4) indicated the placement of methyl group at the N5 nitrogen atom.

Experimental

1D and 2D NMR spectra were recorded on a Varian Unity 500 spectrometer. The title compound was prepared according to the previously described procedure (Sączewski & Foks, 1981); m.p. 492–494 K (decomp.); 1H NMR (500 MHz, DMSO-d6, see Fig. 3 for numbering scheme) δH 6.94 (1H, d, J = 7.2 Hz, H12), 6.22–6.19 (1H, ddd, J=9.8, 6.8, ~1 Hz, H10), 5.86 (1H, t, J = 1 Hz, H8a), 5.67 (1H, dd, J = 9.8, ~1 Hz, H9), 5.41–5.38 (1H, dd, J = 7.2, 6.8 Hz, H11), 4.42 (1H, dt, J = 9.3, 6.8 Hz, H2), 4.20 (1H, dt, J = 9.3, 6.8 Hz, H2), 4.01–3.83 (4H, m, H7, H6, 2xH3),3.78–3.71 (1H, m, H6), 3.49–3.43 (1H, m, H7), 3.26 (3H, s, CH3); 13C NMR (125 MHz, DMSO-d6, see Fig. 3 for numbering scheme) δC 152.6 (C4a), 145.7 (C13a), 125.4 (C12), 124.8 (C10), 113.6 (C9), 103.4 (C11), 67.0 (C8a), 51.7 (C3), 50.7 (C6), 46.6 (C2), 43.3 (C7), 33.7 (C14); IR (KBr, cm–1): 3090, 3079, 3025, 2936, 2880, 1684, 1661, 1550, 1429, 1321, 1301, 1186, 677.

Refinement

The twin matrix, -1 0 0/0 - 1 0/0.115 0 1, corresponding to 180° rotation about [0 0 1] direct lattice direction has been determined with the program ROTAX (Cooper et al., 2002). For the refinement with the SHELXL97 program (Sheldrick, 2008), the reflection data file was prepared in the HKLF 5 format using the 'Make HKLF5' function of the WinGX program (Farrugia, 1999). The overlapping reflections and those belonging to only one twin domain are used in the refinement (HKLF 5 format of SHELXL97). Those which were excluded, 132 reflections, are partial overlaps which could not be integrated properly at the data processing stage. The BASF parameter refined at 0.1559 (12). The H atoms bonded to C atoms were placed at calculated positions, with C—H = 0.95–1.00 Å, and refined as riding on their parent atoms, with Uiso(H) = x Ueq(C), where x = 1.5 for the H atoms from the methyl group and x = 1.2 for the remaining H atoms. The maximum and minimum residual electron-density peaks of 1.74 and -1.24 eÅ-3 were located 0.72 Å and 1.84 Å from H6B and I1 atoms, respectively.

Figures

Fig. 1.
Reaction of 2,3,6,7,8a,13-hexahydropyrido[1,2-a]diimidazo[1',2',-c:1",2"-e]-1,3,5-triazine (1) with methyl iodide.
Fig. 2.
Asymmetric unit for the title salt with displacement ellipsoids shown at the 50% probability level.
Fig. 3.
HSQC spectrum of the title compound 2
Fig. 4.
HMBC spectrum of the title compound 2

Crystal data

C12H16N5+·IF(000) = 704
Mr = 357.20Dx = 1.765 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 19213 reflections
a = 7.6299 (2) Åθ = 2.7–32.3°
b = 15.3939 (4) ŵ = 2.37 mm1
c = 11.4503 (3) ÅT = 100 K
β = 92.204 (2)°Block, colourless
V = 1343.89 (6) Å30.2 × 0.2 × 0.1 mm
Z = 4

Data collection

Oxford Diffraction Xcalibur-E CCD diffractometer4406 independent reflections
Radiation source: fine-focus sealed tube4018 reflections with I > 2σ(I)
graphiteRint = 0.026
ω scanθmax = 32.4°, θmin = 4.1°
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009)h = −9→11
Tmin = 0.496, Tmax = 0.789k = −23→23
25955 measured reflectionsl = 0→16

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.029Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.070H-atom parameters constrained
S = 1.20w = 1/[σ2(Fo2) + (0.0196P)2 + 3.1405P] where P = (Fo2 + 2Fc2)/3
4406 reflections(Δ/σ)max = 0.001
165 parametersΔρmax = 1.74 e Å3
0 restraintsΔρmin = −1.24 e Å3

Special details

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

xyzUiso*/Ueq
I10.04305 (2)0.194494 (11)0.473423 (14)0.01657 (5)
N10.1806 (3)0.53774 (16)0.3251 (2)0.0209 (5)
C20.2057 (4)0.4944 (2)0.2120 (2)0.0222 (5)
H2A0.29100.52720.16600.027*
H2B0.09310.49140.16630.027*
C30.2755 (4)0.40179 (19)0.2385 (2)0.0206 (5)
H3A0.18690.35690.21730.025*
H3B0.38460.38980.19730.025*
N40.3083 (3)0.40681 (15)0.36610 (19)0.0155 (4)
N50.4690 (3)0.27675 (15)0.4159 (2)0.0162 (4)
C60.5326 (4)0.23510 (18)0.5250 (2)0.0189 (5)
H6A0.66230.23160.52890.023*
H6B0.48370.17590.53220.023*
C70.4659 (4)0.29506 (18)0.6205 (2)0.0201 (5)
H7A0.36770.26790.66130.024*
H7B0.56090.30970.67850.024*
N80.4068 (3)0.37245 (14)0.55467 (19)0.0147 (4)
C90.3144 (4)0.4560 (2)0.7238 (2)0.0202 (5)
H90.37520.41750.77590.024*
C100.2718 (4)0.5354 (2)0.7605 (3)0.0237 (6)
H100.29380.55100.84000.028*
C110.1922 (4)0.59810 (19)0.6798 (3)0.0237 (6)
H110.14620.65100.70820.028*
C120.1842 (4)0.58081 (18)0.5651 (3)0.0197 (5)
H120.13630.62260.51180.024*
N130.2459 (3)0.50171 (14)0.5233 (2)0.0162 (4)
C140.2675 (3)0.42666 (17)0.6013 (2)0.0151 (4)
H140.15560.39280.60100.018*
C150.3916 (3)0.35088 (16)0.4392 (2)0.0136 (4)
C160.2403 (3)0.48697 (17)0.4045 (2)0.0156 (5)
C170.4863 (4)0.2302 (2)0.3064 (3)0.0242 (6)
H17A0.38540.19160.29340.036*
H17B0.59440.19570.31020.036*
H17C0.49090.27190.24200.036*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
I10.01712 (8)0.01865 (8)0.01406 (7)0.00055 (6)0.00212 (5)−0.00050 (6)
N10.0239 (12)0.0181 (11)0.0207 (11)0.0010 (9)−0.0007 (9)0.0040 (9)
C20.0251 (14)0.0244 (14)0.0170 (12)0.0007 (11)−0.0009 (10)0.0062 (11)
C30.0271 (15)0.0233 (14)0.0114 (11)0.0015 (11)−0.0001 (9)0.0007 (10)
N40.0198 (11)0.0150 (10)0.0117 (9)0.0004 (8)0.0010 (7)0.0016 (8)
N50.0174 (11)0.0158 (9)0.0155 (9)0.0029 (8)0.0033 (8)0.0009 (8)
C60.0189 (13)0.0187 (12)0.0191 (12)0.0056 (10)0.0012 (9)0.0035 (9)
C70.0245 (13)0.0194 (12)0.0161 (11)0.0044 (10)−0.0008 (9)0.0045 (9)
N80.0157 (10)0.0150 (9)0.0134 (9)0.0007 (8)−0.0001 (7)0.0017 (7)
C90.0213 (13)0.0242 (13)0.0152 (11)−0.0016 (10)0.0003 (9)−0.0024 (10)
C100.0223 (14)0.0297 (15)0.0191 (13)−0.0052 (11)0.0023 (10)−0.0092 (11)
C110.0241 (15)0.0162 (12)0.0312 (15)−0.0029 (10)0.0048 (11)−0.0088 (11)
C120.0178 (13)0.0126 (11)0.0289 (14)−0.0021 (9)0.0045 (10)−0.0026 (10)
N130.0212 (11)0.0111 (9)0.0164 (10)0.0001 (8)0.0001 (8)−0.0002 (8)
C140.0166 (12)0.0152 (11)0.0135 (11)−0.0006 (9)0.0001 (8)−0.0001 (9)
C150.0113 (11)0.0147 (11)0.0148 (10)−0.0024 (8)0.0022 (8)0.0012 (8)
C160.0157 (12)0.0130 (11)0.0181 (11)−0.0021 (9)0.0012 (9)0.0011 (9)
C170.0316 (16)0.0213 (13)0.0201 (12)0.0047 (11)0.0075 (11)−0.0047 (10)

Geometric parameters (Å, °)

N1—C161.270 (3)C7—H7B0.9900
N1—C21.476 (4)N8—C151.364 (3)
C2—C31.547 (4)N8—C141.468 (3)
C2—H2A0.9900C9—C101.336 (4)
C2—H2B0.9900C9—C141.504 (4)
C3—N41.475 (3)C9—H90.9500
C3—H3A0.9900C10—C111.453 (5)
C3—H3B0.9900C10—H100.9500
N4—C151.344 (3)C11—C121.340 (4)
N4—C161.415 (3)C11—H110.9500
N5—C151.317 (3)C12—N131.397 (3)
N5—C171.455 (4)C12—H120.9500
N5—C61.470 (3)N13—C161.378 (3)
C6—C71.533 (4)N13—C141.466 (3)
C6—H6A0.9900C14—H141.0000
C6—H6B0.9900C17—H17A0.9800
C7—N81.471 (3)C17—H17B0.9800
C7—H7A0.9900C17—H17C0.9800
C16—N1—C2107.1 (2)C10—C9—C14121.1 (3)
N1—C2—C3107.4 (2)C10—C9—H9119.4
N1—C2—H2A110.2C14—C9—H9119.4
C3—C2—H2A110.2C9—C10—C11120.5 (3)
N1—C2—H2B110.2C9—C10—H10119.7
C3—C2—H2B110.2C11—C10—H10119.7
H2A—C2—H2B108.5C12—C11—C10119.6 (3)
N4—C3—C2101.0 (2)C12—C11—H11120.2
N4—C3—H3A111.6C10—C11—H11120.2
C2—C3—H3A111.6C11—C12—N13120.4 (3)
N4—C3—H3B111.6C11—C12—H12119.8
C2—C3—H3B111.6N13—C12—H12119.8
H3A—C3—H3B109.4C16—N13—C12118.9 (2)
C15—N4—C16122.4 (2)C16—N13—C14118.1 (2)
C15—N4—C3129.9 (2)C12—N13—C14120.6 (2)
C16—N4—C3107.6 (2)N13—C14—N8107.0 (2)
C15—N5—C17131.1 (2)N13—C14—C9110.4 (2)
C15—N5—C6110.0 (2)N8—C14—C9111.1 (2)
C17—N5—C6118.7 (2)N13—C14—H14109.4
N5—C6—C7103.6 (2)N8—C14—H14109.4
N5—C6—H6A111.0C9—C14—H14109.4
C7—C6—H6A111.0N5—C15—N4129.4 (2)
N5—C6—H6B111.0N5—C15—N8112.7 (2)
C7—C6—H6B111.0N4—C15—N8117.9 (2)
H6A—C6—H6B109.0N1—C16—N13127.0 (3)
N8—C7—C6103.0 (2)N1—C16—N4116.1 (2)
N8—C7—H7A111.2N13—C16—N4116.9 (2)
C6—C7—H7A111.2N5—C17—H17A109.5
N8—C7—H7B111.2N5—C17—H17B109.5
C6—C7—H7B111.2H17A—C17—H17B109.5
H7A—C7—H7B109.1N5—C17—H17C109.5
C15—N8—C14117.1 (2)H17A—C17—H17C109.5
C15—N8—C7108.2 (2)H17B—C17—H17C109.5
C14—N8—C7119.1 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C3—H3B···I1i0.993.154.007 (3)145
C6—H6A···I1ii0.993.054.010 (3)163
C9—H9···I1iii0.953.084.025 (3)172
C12—H12···I1iv0.953.143.887 (3)137
C17—H17C···I1i0.983.164.025 (3)148

Symmetry codes: (i) x+1/2, −y+1/2, z−1/2; (ii) x+1, y, z; (iii) x+1/2, −y+1/2, z+1/2; (iv) −x, −y+1, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: TK2676).

References

  • Cooper, R. I., Gould, R. O., Parsons, S. & Watkin, D. J. (2002). J. Appl. Cryst.35, 168–174.
  • Farrugia, L. J. (1997). J. Appl. Cryst.30, 565.
  • Farrugia, L. J. (1999). J. Appl. Cryst.32, 837–838.
  • Oxford Diffraction (2009). CrysAlis PRO Oxford Diffraction Ltd, Yarnton, England.
  • Sączewski, F. & Foks, H. (1981). Synthesis, pp. 151–152.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]

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