Crystal structure of 4,6-di-amino-2,2-dimethyl-3-[3-(2,4,5-tri-chloro-phen-oxy)prop-oxy]-2,3-di-hydro-1,3,5-triazin-1-ium chloride methanol monosolvate.

In the title methanol-solvated salt, C14H19Cl3N5O2 (+)·Cl(-)·CH3OH, the triazine mol-ecule is protonated at one of the triazine N atoms. In the crystal, the triazine cations are linked through a pair of N-H⋯N hydrogen bonds, with graph-set R 2 (2)(8), forming an inversion dimer. The protonated N atom and the 2- and 4-amino groups of the triazine cation inter-act with the chloride anion through N-H⋯Cl hydrogen bonds, leading to the formation of a tape structure running along the b-axis direction. A short Cl⋯Cl contact [3.2937 (9) Å] is observed in the tape. The methanol mol-ecule is linked to the chloride anion and the triazine cation, respectively, by an O-H⋯Cl hydrogen bond and a C-H⋯O inter-action.

Related literature

For anti­folate anti­malarial drugs, see: Toyoda et al. (1997 ▸); Yuthavong (2002 ▸). For anti­folate drug resistance, see: Nzila (2006 ▸); Rieckmann et al. (1996 ▸). For our previous work on the protein crystallographic analysis of di­hydro­folate reductase, see: Yuvaniyama et al. (2003 ▸); Kongsaeree et al. (2005 ▸).

Experimental

Crystal data

C14H19Cl3N5O2 +·Cl−·CH4O

M = 463.18

Triclinic,

a = 8.5930 (4) Å

b = 9.3510 (3) Å

c = 14.6970 (7) Å

α = 75.422 (3)°

β = 78.2260 (19)°

γ = 70.194 (3)°

V = 1066.13 (8) Å3

Z = 2

Mo Kα radiation

μ = 0.58 mm−1

T = 298 K

0.32 × 0.20 × 0.18 mm

Data collection

Nonius KappaCCD diffractometer

5032 measured reflections

2935 independent reflections

2681 reflections with I > 2σ(I)

R int = 0.017

θmax = 23.3°

Refinement

R[F 2 > 2σ(F 2)] = 0.034

wR(F 2) = 0.087

S = 1.06

2935 reflections

268 parameters

6 restraints

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.26 e Å−3

Δρmin = −0.26 e Å−3

Data collection: KappaCCD Software (Nonius, 1999 ▸); cell refinement: SCALEPACK (Otwinowski & Minor, 1997 ▸); data reduction: DENZO (Otwinowski & Minor, 1997 ▸); program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▸); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015 ▸); molecular graphics: PLATON (Spek, 2009 ▸); software used to prepare material for publication: publCIF (Westrip, 2010 ▸).

Crystal structure: contains datablock(s) I, New_Global_Publ_Block. DOI: 10.1107/S205698901501378X/is5407sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S205698901501378X/is5407Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S205698901501378X/is5407Isup3.cml

Click here for additional data file.

. DOI: 10.1107/S205698901501378X/is5407fig1.tif

View of the mol­ecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level.

Click here for additional data file.

. DOI: 10.1107/S205698901501378X/is5407fig2.tif

Hydrogen bonding inter­actions, showing mol­ecules linked through N—H⋯N, N—H⋯Cl and O—H⋯Cl (dashed lines), and C—H⋯O (dotted line) hydrogen bonds.

CCDC reference: 1414045

Additional supporting information: crystallographic information; 3D view; checkCIF report

C14H19Cl3N5O2+·Cl−·CH4O	Z = 2
Mr = 463.18	F(000) = 480
Triclinic, P1	Dx = 1.443 Mg m−3
a = 8.5930 (4) Å	Mo Kα radiation, λ = 0.71073 Å
b = 9.3510 (3) Å	Cell parameters from 2724 reflections
c = 14.6970 (7) Å	θ = 2.9–23.3°
α = 75.422 (3)°	µ = 0.58 mm−1
β = 78.2260 (19)°	T = 298 K
γ = 70.194 (3)°	Rod, colourless
V = 1066.13 (8) Å3	0.32 × 0.20 × 0.18 mm

Nonius KappaCCD diffractometer	2681 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.017
Detector resolution: 9 pixels mm-1	θmax = 23.3°, θmin = 3.1°
CCD scans	h = −9→9
5032 measured reflections	k = −10→9
2935 independent reflections	l = −16→16

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.034	Hydrogen site location: mixed
wR(F2) = 0.087	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ2(Fo2) + (0.0351P)2 + 0.5001P] where P = (Fo2 + 2Fc2)/3
2935 reflections	(Δ/σ)max = 0.001
268 parameters	Δρmax = 0.26 e Å−3
6 restraints	Δρmin = −0.26 e Å−3

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.

	x	y	z	Uiso*/Ueq
Cl1	−0.26674 (7)	−0.09037 (6)	0.98859 (4)	0.05048 (18)
Cl2	−0.50317 (9)	0.36361 (7)	1.18779 (4)	0.0669 (2)
Cl3	−0.27290 (9)	0.54749 (7)	1.04479 (5)	0.0658 (2)
Cl4	0.17598 (7)	0.43814 (6)	0.40327 (4)	0.05568 (19)
O1	0.36692 (15)	0.10928 (15)	0.69350 (9)	0.0364 (3)
O2	−0.07327 (17)	0.09663 (16)	0.86849 (10)	0.0423 (3)
O3	0.0138 (3)	0.4448 (3)	0.22657 (17)	0.0928 (7)
H3	0.0601	0.4417	0.2709	0.139*
N1	0.6726 (2)	0.30658 (19)	0.58733 (12)	0.0404 (4)
N2	0.9243 (2)	0.2208 (2)	0.49858 (14)	0.0459 (4)
N3	0.77155 (19)	0.05192 (18)	0.56004 (11)	0.0369 (4)
N4	0.5995 (2)	−0.1015 (2)	0.61841 (14)	0.0491 (5)
N5	0.49520 (18)	0.15639 (17)	0.62848 (11)	0.0327 (4)
C1	0.7877 (2)	0.1939 (2)	0.54981 (13)	0.0338 (4)
C2	0.6256 (2)	0.0339 (2)	0.60370 (13)	0.0334 (4)
C3	0.5346 (2)	0.2785 (2)	0.65866 (14)	0.0356 (4)
C4	0.5862 (3)	0.2234 (3)	0.75760 (15)	0.0501 (5)
H4C	0.4938	0.2043	0.8026	0.060*
H4D	0.6195	0.3015	0.7732	0.060*
H4E	0.6779	0.1294	0.7596	0.060*
C5	0.3872 (3)	0.4247 (2)	0.65107 (18)	0.0509 (6)
H5A	0.2982	0.4096	0.7001	0.061*
H5B	0.3498	0.4478	0.5903	0.061*
H5C	0.4200	0.5094	0.6580	0.061*
C6	0.2207 (2)	0.1419 (3)	0.64724 (14)	0.0422 (5)
H6A	0.2490	0.0902	0.5939	0.051*
H6B	0.1740	0.2525	0.6248	0.051*
C7	0.0993 (2)	0.0797 (3)	0.72291 (15)	0.0421 (5)
H7A	0.0103	0.0749	0.6935	0.051*
H7B	0.1564	−0.0249	0.7532	0.051*
C8	0.0247 (3)	0.1781 (2)	0.79714 (14)	0.0418 (5)
H8A	0.1119	0.1912	0.8241	0.050*
H8B	−0.0448	0.2796	0.7698	0.050*
C9	−0.1674 (2)	0.1672 (2)	0.94055 (13)	0.0348 (4)
C10	−0.2683 (2)	0.0871 (2)	1.00452 (13)	0.0349 (4)
C11	−0.3698 (3)	0.1481 (2)	1.07983 (14)	0.0405 (5)
H11	−0.4368	0.0939	1.1217	0.049*
C12	−0.3719 (3)	0.2895 (2)	1.09306 (14)	0.0419 (5)
C13	−0.2726 (3)	0.3696 (2)	1.02998 (14)	0.0418 (5)
C14	−0.1711 (3)	0.3094 (2)	0.95396 (14)	0.0407 (5)
H14	−0.1053	0.3647	0.9118	0.049*
C15	0.0334 (5)	0.2948 (4)	0.2183 (3)	0.1067 (12)
H15A	−0.0107	0.2981	0.1625	0.160*
H15B	−0.0254	0.2456	0.2732	0.160*
H15C	0.1498	0.2369	0.2133	0.160*
H1	0.700 (3)	0.3881 (18)	0.5866 (17)	0.053 (7)*
H2A	0.944 (3)	0.3083 (16)	0.4926 (16)	0.045 (6)*
H2B	1.002 (2)	0.144 (2)	0.4770 (16)	0.052 (7)*
H4A	0.680 (2)	−0.181 (2)	0.6007 (17)	0.057 (7)*
H4B	0.507 (2)	−0.108 (3)	0.6546 (16)	0.067 (8)*

	U11	U22	U33	U12	U13	U23
Cl1	0.0612 (4)	0.0386 (3)	0.0568 (3)	−0.0254 (3)	0.0059 (3)	−0.0153 (2)
Cl2	0.0924 (5)	0.0554 (4)	0.0519 (4)	−0.0290 (3)	0.0215 (3)	−0.0243 (3)
Cl3	0.0963 (5)	0.0422 (3)	0.0678 (4)	−0.0344 (3)	0.0018 (3)	−0.0180 (3)
Cl4	0.0613 (4)	0.0410 (3)	0.0719 (4)	−0.0260 (3)	0.0097 (3)	−0.0241 (3)
O1	0.0292 (7)	0.0467 (8)	0.0340 (7)	−0.0173 (6)	0.0032 (5)	−0.0070 (6)
O2	0.0422 (8)	0.0407 (8)	0.0426 (8)	−0.0178 (6)	0.0095 (6)	−0.0107 (6)
O3	0.1093 (18)	0.0790 (15)	0.0964 (17)	−0.0336 (13)	−0.0224 (13)	−0.0144 (12)
N1	0.0407 (9)	0.0317 (9)	0.0515 (10)	−0.0178 (8)	0.0047 (8)	−0.0123 (8)
N2	0.0406 (10)	0.0400 (11)	0.0577 (11)	−0.0220 (9)	0.0091 (8)	−0.0093 (9)
N3	0.0341 (9)	0.0332 (9)	0.0432 (9)	−0.0151 (7)	0.0078 (7)	−0.0109 (7)
N4	0.0443 (11)	0.0340 (10)	0.0682 (13)	−0.0196 (9)	0.0168 (9)	−0.0172 (9)
N5	0.0283 (8)	0.0344 (9)	0.0365 (8)	−0.0138 (7)	0.0058 (6)	−0.0111 (7)
C1	0.0334 (10)	0.0335 (11)	0.0346 (10)	−0.0140 (9)	0.0008 (8)	−0.0060 (8)
C2	0.0354 (10)	0.0323 (10)	0.0335 (10)	−0.0135 (8)	0.0018 (8)	−0.0086 (8)
C3	0.0337 (10)	0.0342 (10)	0.0408 (11)	−0.0117 (8)	0.0014 (8)	−0.0138 (8)
C4	0.0487 (13)	0.0593 (14)	0.0474 (13)	−0.0177 (11)	−0.0071 (10)	−0.0173 (11)
C5	0.0450 (12)	0.0382 (12)	0.0661 (15)	−0.0051 (10)	−0.0028 (11)	−0.0183 (10)
C6	0.0342 (11)	0.0594 (13)	0.0372 (11)	−0.0190 (10)	−0.0018 (8)	−0.0124 (9)
C7	0.0345 (11)	0.0544 (13)	0.0433 (11)	−0.0211 (9)	−0.0007 (9)	−0.0130 (10)
C8	0.0373 (11)	0.0454 (12)	0.0425 (11)	−0.0194 (9)	0.0047 (9)	−0.0068 (9)
C9	0.0326 (10)	0.0356 (11)	0.0358 (10)	−0.0116 (8)	−0.0022 (8)	−0.0065 (8)
C10	0.0379 (11)	0.0301 (10)	0.0379 (11)	−0.0124 (8)	−0.0048 (8)	−0.0061 (8)
C11	0.0458 (12)	0.0398 (12)	0.0368 (11)	−0.0210 (9)	0.0022 (9)	−0.0039 (9)
C12	0.0503 (12)	0.0394 (12)	0.0356 (11)	−0.0151 (10)	−0.0002 (9)	−0.0091 (9)
C13	0.0526 (12)	0.0325 (11)	0.0431 (12)	−0.0162 (9)	−0.0068 (10)	−0.0073 (9)
C14	0.0428 (11)	0.0379 (11)	0.0425 (11)	−0.0202 (9)	−0.0007 (9)	−0.0030 (9)
C15	0.152 (4)	0.064 (2)	0.120 (3)	−0.035 (2)	−0.050 (3)	−0.0171 (19)

Cl1—C10	1.7290 (19)	C4—H4D	0.9600
Cl2—C12	1.734 (2)	C4—H4E	0.9600
Cl3—C13	1.730 (2)	C5—H5A	0.9600
O1—N5	1.4177 (19)	C5—H5B	0.9600
O1—C6	1.455 (2)	C5—H5C	0.9600
O2—C9	1.361 (2)	C6—C7	1.509 (3)
O2—C8	1.436 (2)	C6—H6A	0.9700
O3—C15	1.389 (4)	C6—H6B	0.9700
O3—H3	0.8200	C7—C8	1.506 (3)
N1—C1	1.325 (3)	C7—H7A	0.9700
N1—C3	1.462 (2)	C7—H7B	0.9700
N1—H1	0.866 (10)	C8—H8A	0.9700
N2—C1	1.324 (2)	C8—H8B	0.9700
N2—H2A	0.868 (10)	C9—C14	1.382 (3)
N2—H2B	0.874 (10)	C9—C10	1.396 (3)
N3—C2	1.332 (2)	C10—C11	1.377 (3)
N3—C1	1.349 (2)	C11—C12	1.378 (3)
N4—C2	1.317 (3)	C11—H11	0.9300
N4—H4A	0.883 (10)	C12—C13	1.381 (3)
N4—H4B	0.873 (10)	C13—C14	1.383 (3)
N5—C2	1.369 (2)	C14—H14	0.9300
N5—C3	1.481 (2)	C15—H15A	0.9600
C3—C5	1.514 (3)	C15—H15B	0.9600
C3—C4	1.519 (3)	C15—H15C	0.9600
C4—H4C	0.9600
N5—O1—C6	110.75 (13)	O1—C6—H6A	110.8
C9—O2—C8	118.27 (15)	C7—C6—H6A	110.8
C15—O3—H3	109.5	O1—C6—H6B	110.8
C1—N1—C3	122.30 (16)	C7—C6—H6B	110.8
C1—N1—H1	117.3 (16)	H6A—C6—H6B	108.9
C3—N1—H1	116.2 (16)	C8—C7—C6	112.46 (17)
C1—N2—H2A	121.4 (15)	C8—C7—H7A	109.1
C1—N2—H2B	118.5 (16)	C6—C7—H7A	109.1
H2A—N2—H2B	120 (2)	C8—C7—H7B	109.1
C2—N3—C1	116.03 (16)	C6—C7—H7B	109.1
C2—N4—H4A	119.9 (16)	H7A—C7—H7B	107.8
C2—N4—H4B	114.9 (18)	O2—C8—C7	105.97 (16)
H4A—N4—H4B	124 (2)	O2—C8—H8A	110.5
C2—N5—O1	112.83 (14)	C7—C8—H8A	110.5
C2—N5—C3	117.77 (15)	O2—C8—H8B	110.5
O1—N5—C3	110.56 (13)	C7—C8—H8B	110.5
N2—C1—N1	119.24 (17)	H8A—C8—H8B	108.7
N2—C1—N3	117.74 (17)	O2—C9—C14	125.37 (17)
N1—C1—N3	123.01 (16)	O2—C9—C10	115.84 (17)
N4—C2—N3	120.33 (17)	C14—C9—C10	118.79 (18)
N4—C2—N5	118.00 (17)	C11—C10—C9	120.85 (18)
N3—C2—N5	121.51 (16)	C11—C10—Cl1	119.59 (14)
N1—C3—N5	103.00 (14)	C9—C10—Cl1	119.56 (15)
N1—C3—C5	108.81 (16)	C10—C11—C12	120.00 (18)
N5—C3—C5	109.49 (16)	C10—C11—H11	120.0
N1—C3—C4	111.45 (16)	C12—C11—H11	120.0
N5—C3—C4	111.35 (16)	C11—C12—C13	119.49 (18)
C5—C3—C4	112.31 (18)	C11—C12—Cl2	118.64 (15)
C3—C4—H4C	109.5	C13—C12—Cl2	121.85 (16)
C3—C4—H4D	109.5	C12—C13—C14	120.82 (18)
H4C—C4—H4D	109.5	C12—C13—Cl3	120.49 (16)
C3—C4—H4E	109.5	C14—C13—Cl3	118.68 (15)
H4C—C4—H4E	109.5	C9—C14—C13	120.05 (18)
H4D—C4—H4E	109.5	C9—C14—H14	120.0
C3—C5—H5A	109.5	C13—C14—H14	120.0
C3—C5—H5B	109.5	O3—C15—H15A	109.5
H5A—C5—H5B	109.5	O3—C15—H15B	109.5
C3—C5—H5C	109.5	H15A—C15—H15B	109.5
H5A—C5—H5C	109.5	O3—C15—H15C	109.5
H5B—C5—H5C	109.5	H15A—C15—H15C	109.5
O1—C6—C7	104.82 (15)	H15B—C15—H15C	109.5
C6—O1—N5—C2	−107.86 (18)	O1—C6—C7—C8	72.4 (2)
C6—O1—N5—C3	117.90 (17)	C9—O2—C8—C7	−174.20 (16)
C3—N1—C1—N2	−168.24 (18)	C6—C7—C8—O2	−174.17 (16)
C3—N1—C1—N3	12.8 (3)	C8—O2—C9—C14	−3.3 (3)
C2—N3—C1—N2	−173.42 (18)	C8—O2—C9—C10	176.05 (17)
C2—N3—C1—N1	5.6 (3)	O2—C9—C10—C11	−179.53 (18)
C1—N3—C2—N4	−178.78 (19)	C14—C9—C10—C11	−0.1 (3)
C1—N3—C2—N5	5.9 (3)	O2—C9—C10—Cl1	0.1 (2)
O1—N5—C2—N4	19.0 (2)	C14—C9—C10—Cl1	179.54 (15)
C3—N5—C2—N4	149.69 (18)	C9—C10—C11—C12	−0.3 (3)
O1—N5—C2—N3	−165.59 (16)	Cl1—C10—C11—C12	−179.98 (16)
C3—N5—C2—N3	−34.9 (3)	C10—C11—C12—C13	0.5 (3)
C1—N1—C3—N5	−35.7 (2)	C10—C11—C12—Cl2	179.18 (16)
C1—N1—C3—C5	−151.85 (19)	C11—C12—C13—C14	−0.1 (3)
C1—N1—C3—C4	83.8 (2)	Cl2—C12—C13—C14	−178.82 (17)
C2—N5—C3—N1	45.5 (2)	C11—C12—C13—Cl3	179.94 (17)
O1—N5—C3—N1	177.24 (14)	Cl2—C12—C13—Cl3	1.3 (3)
C2—N5—C3—C5	161.15 (17)	O2—C9—C14—C13	179.80 (18)
O1—N5—C3—C5	−67.12 (19)	C10—C9—C14—C13	0.4 (3)
C2—N5—C3—C4	−74.1 (2)	C12—C13—C14—C9	−0.3 (3)
O1—N5—C3—C4	57.68 (19)	Cl3—C13—C14—C9	179.62 (16)
N5—O1—C6—C7	177.50 (15)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···Cl4i	0.87 (1)	2.27 (1)	3.1236 (17)	167 (2)
N2—H2A···Cl4ii	0.87 (1)	2.64 (2)	3.3285 (17)	137 (2)
N2—H2B···N3iii	0.87 (1)	2.26 (1)	3.122 (2)	170 (2)
N4—H4A···Cl4iv	0.88 (1)	2.31 (1)	3.1419 (19)	158 (2)
O3—H3···Cl4	0.82	2.35	3.166 (2)	176
C14—H14···O3v	0.93	2.53	3.423 (3)	161

Table 1

Hydrogen-bond geometry (, )

DHA	DH	HA	D A	DHA
N1H1Cl4i	0.87(1)	2.27(1)	3.1236(17)	167(2)
N2H2ACl4ii	0.87(1)	2.64(2)	3.3285(17)	137(2)
N2H2BN3iii	0.87(1)	2.26(1)	3.122(2)	170(2)
N4H4ACl4iv	0.88(1)	2.31(1)	3.1419(19)	158(2)
O3H3Cl4	0.82	2.35	3.166(2)	176
C14H14O3v	0.93	2.53	3.423(3)	161

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) .