Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807052397/hb2608sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807052397/hb2608Isup2.hkl |
CCDC reference: 257040
Key indicators
- Single-crystal X-ray study
- T = 120 K
- Mean (C-C) = 0.018 Å
- R factor = 0.056
- wR factor = 0.056
- Data-to-parameter ratio = 7.4
checkCIF/PLATON results
No syntax errors found
Alert level B PLAT026_ALERT_3_B Ratio Observed / Unique Reflections too Low .... 34 Perc. PLAT340_ALERT_3_B Low Bond Precision on C-C Bonds (x 1000) Ang ... 18
Alert level C PLAT066_ALERT_1_C Predicted and Reported Transmissions Identical . ? PLAT089_ALERT_3_C Poor Data / Parameter Ratio (Zmax .LT. 18) ..... 7.38 PLAT152_ALERT_1_C Supplied and Calc Volume s.u. Inconsistent ..... ? PLAT244_ALERT_4_C Low 'Solvent' Ueq as Compared to Neighbors for C16 PLAT369_ALERT_2_C Long C(sp2)-C(sp2) Bond C16 - C20 ... 1.53 Ang.
Alert level G REFLT03_ALERT_4_G WARNING: Large fraction of Friedel related reflns may be needed to determine absolute structure From the CIF: _diffrn_reflns_theta_max 25.00 From the CIF: _reflns_number_total 1807 Count of symmetry unique reflns 1809 Completeness (_total/calc) 99.89% TEST3: Check Friedels for noncentro structure Estimate of Friedel pairs measured 0 Fraction of Friedel pairs measured 0.000 Are heavy atom types Z>Si present yes PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints ....... 4
0 ALERT level A = In general: serious problem 2 ALERT level B = Potentially serious problem 5 ALERT level C = Check and explain 2 ALERT level G = General alerts; check 2 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 1 ALERT type 2 Indicator that the structure model may be wrong or deficient 4 ALERT type 3 Indicator that the structure quality may be low 2 ALERT type 4 Improvement, methodology, query or suggestion 0 ALERT type 5 Informative message, check
For related literature, see: Bernstein et al. (1995); De et al. (1989); Devi et al. (2007); Olliaro (2001); Sansom et al. (1989); Sethuraman & Muthiah (2002).
Hot methanolic solutions of pyrimethamine (62 mg) and nicotinic acid (31 mg) were mixed in a 1:1 ratio. The resultant mixture was warmed over a water bath for 15 minutes and kept at room temperature for crystallization. After a few days colourless blocks of (I) were obtained.
The C– and N-bound hydrogen atoms were fixed geometrically (C—H = 0.93–0.96 Å, N—H = 0.86 Å) and refined as riding with Uiso(H) = 1.2Ueq(carrier). The water hydrogen atoms were located from a difference map and were refined with isotropic thermal parameters.
Pyrimethamine [2,4-diamino-5-(p-chlorophenyl)-6-ethylpyrimidine] is an antifolate drug used in anti-malarial chemotherapy (Olliaro, 2001). The crystal structure of pyrimethamine (PMN) has been reported from our laboratory (Sethuraman & Muthiah, 2002) as have the structures of various protonated PMN salts (e.g. Devi et al., 2007). As part of these ongoing studies, the synthesis and structure of the title compound, (I), is now described.
The asymmetric unit of (I) contains a protonated pyrimethaminium (PMN) cation, nicotinate anion and a water molecule (Fig. 1). The PMN is protonated at N1 as it is evident from the enhancement of the C—N—C from 116.3 (2)° in neutral PMN molecule A and 116.09 (18)° in molecule B (Sethuraman & Muthiah, 2002) to 119.9 (10)° in (I). The dihedral angle between the 2,4-diamino pyrimidine and p-chlorophenyl rings is 70.3 (6)°. The torsion angle C5—C6—C7—C8, which represents the deviation of the ethyl group from the pyrimidine ring is 77.6 (16)°. The values are close to the results of modeling studies of DHFR-PMN complexes (Sansom et al., 1989). The C5—C9 bond length connecting the pyrimidine and phenyl ring in (I) is 1.472 (2) Å, in agreement with related structutres (De et al., 1989). The protonated N1 cation interacts with the carboxylate group of the nicotinate ion via N—H···O hydrogen bonds forming cyclic hydrogen bonded ring motif represented by graph-set notation R22(8) (Bernstein et al., 1995). The oxygen atom of the nicotinate anion bridges the 2-amino, 4-amino group of the PMN cation and water molecule forming a hydrogen bonded ring motif with graph-set notation R42(8). The frequently occurring R22(8) motif and R42(8) motif combine to form another motif, namely a DDA array (Fig. 2). Furthermore, the nicotinate anion and water molecule form a one dimensional supramolecular chain involving N—H···O and O—H···N hydrogen bonds (Fig. 3). π-π interactions between the aromatic rings are observed. The pyrimidine ring of PMN stacks with the nicotinate ring with a perpendicular separation of 3.551 Å, centroid-to-centroid distance of 3.637 (6) Å and a slip angle (the angle between the centroid-to-centroid vector and the normal to the plane) 19.05°.
For related literature, see: Bernstein et al. (1995); De et al. (1989); Devi et al. (2007); Olliaro (2001); Sansom et al. (1989); Sethuraman & Muthiah (2002).
Data collection: PW1100 Software (Philips, 1978); cell refinement: PW1100 Software (Philips, 1978); data reduction: PW1100 Software (Philips, 1978); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: PLATON (Spek, 2003).
C12H14ClN4+·C6H4NO2−·H2O | F(000) = 408 |
Mr = 389.84 | Dx = 1.312 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71069 Å |
Hall symbol: P 2yb | Cell parameters from 25 reflections |
a = 6.570 (2) Å | θ = 3.1–25.0° |
b = 16.055 (3) Å | µ = 0.22 mm−1 |
c = 9.480 (2) Å | T = 120 K |
β = 99.19 (3)° | Block, colourless |
V = 987.1 (6) Å3 | 0.23 × 0.20 × 0.18 mm |
Z = 2 |
Philips PW1100 diffractometer | 617 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.059 |
Graphite monochromator | θmax = 25.0°, θmin = 3.1° |
ω scans | h = −7→7 |
Absorption correction: ψ scan (North et al., 1968) | k = 0→19 |
Tmin = 0.951, Tmax = 0.961 | l = 0→11 |
1909 measured reflections | 1 standard reflections every 100 reflections |
1807 independent reflections | intensity decay: none |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: difmap and geom |
R[F2 > 2σ(F2)] = 0.056 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.056 | w = 1/[σ2(Fo2) + (0.0004P)2] where P = (Fo2 + 2Fc2)/3 |
S = 0.85 | (Δ/σ)max < 0.001 |
1807 reflections | Δρmax = 0.20 e Å−3 |
245 parameters | Δρmin = −0.25 e Å−3 |
4 restraints | Absolute structure: Flack (1983), no Friedel pairs |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0.12 (14) |
C12H14ClN4+·C6H4NO2−·H2O | V = 987.1 (6) Å3 |
Mr = 389.84 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 6.570 (2) Å | µ = 0.22 mm−1 |
b = 16.055 (3) Å | T = 120 K |
c = 9.480 (2) Å | 0.23 × 0.20 × 0.18 mm |
β = 99.19 (3)° |
Philips PW1100 diffractometer | 617 reflections with I > 2σ(I) |
Absorption correction: ψ scan (North et al., 1968) | Rint = 0.059 |
Tmin = 0.951, Tmax = 0.961 | 1 standard reflections every 100 reflections |
1909 measured reflections | intensity decay: none |
1807 independent reflections |
R[F2 > 2σ(F2)] = 0.056 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.056 | Δρmax = 0.20 e Å−3 |
S = 0.85 | Δρmin = −0.25 e Å−3 |
1807 reflections | Absolute structure: Flack (1983), no Friedel pairs |
245 parameters | Absolute structure parameter: 0.12 (14) |
4 restraints |
Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All e.s.d.'s are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles |
Refinement. Refinement on F2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The observed criterion of F2 > σ(F2) is used only for calculating -R-factor-obs 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 | 1.3820 (6) | 1.1235 (3) | 1.0788 (4) | 0.0826 (17) | |
N1 | 0.8723 (16) | 0.7185 (6) | 0.6563 (11) | 0.045 (4) | |
N2 | 0.5768 (16) | 0.6658 (6) | 0.5248 (12) | 0.068 (5) | |
N3 | 0.5978 (15) | 0.8085 (6) | 0.5670 (11) | 0.048 (4) | |
N4 | 0.6373 (14) | 0.9479 (6) | 0.5999 (10) | 0.043 (4) | |
C2 | 0.680 (2) | 0.7323 (8) | 0.5826 (14) | 0.046 (5) | |
C4 | 0.7123 (18) | 0.8716 (7) | 0.6251 (12) | 0.034 (5) | |
C5 | 0.9066 (17) | 0.8607 (7) | 0.7163 (12) | 0.033 (4) | |
C6 | 0.9795 (18) | 0.7822 (8) | 0.7277 (12) | 0.039 (5) | |
C7 | 1.181 (2) | 0.7542 (8) | 0.8174 (13) | 0.059 (5) | |
C8 | 1.160 (2) | 0.7484 (10) | 0.9758 (14) | 0.080 (6) | |
C9 | 1.0165 (17) | 0.9297 (7) | 0.7977 (13) | 0.036 (4) | |
C10 | 1.2012 (18) | 0.9616 (7) | 0.7664 (13) | 0.044 (5) | |
C11 | 1.309 (2) | 1.0223 (8) | 0.8517 (15) | 0.058 (6) | |
C12 | 1.232 (2) | 1.0511 (8) | 0.9668 (16) | 0.051 (5) | |
C13 | 1.052 (2) | 1.0240 (8) | 0.9967 (14) | 0.055 (6) | |
C14 | 0.944 (2) | 0.9633 (7) | 0.9141 (13) | 0.048 (5) | |
O1 | 0.7388 (16) | 0.4955 (5) | 0.5855 (10) | 0.064 (4) | |
O2 | 1.0354 (14) | 0.5657 (6) | 0.6448 (10) | 0.062 (4) | |
N5 | 1.042 (2) | 0.2718 (7) | 0.6972 (13) | 0.069 (5) | |
C15 | 0.949 (2) | 0.3422 (8) | 0.6563 (14) | 0.050 (5) | |
C16 | 1.0447 (18) | 0.4212 (8) | 0.6779 (11) | 0.033 (4) | |
C17 | 1.252 (2) | 0.4217 (9) | 0.7387 (12) | 0.051 (5) | |
C18 | 1.346 (2) | 0.3473 (11) | 0.7809 (14) | 0.067 (6) | |
C19 | 1.235 (3) | 0.2749 (9) | 0.7587 (17) | 0.071 (7) | |
C20 | 0.925 (2) | 0.5006 (9) | 0.6307 (14) | 0.052 (6) | |
O1W | 0.1720 (14) | 0.6202 (7) | 0.3881 (12) | 0.068 (4) | |
H1 | 0.92590 | 0.66960 | 0.65760 | 0.0540* | |
H2A | 0.45520 | 0.67150 | 0.47650 | 0.0810* | |
H2B | 0.63200 | 0.61720 | 0.53600 | 0.0810* | |
H4A | 0.51890 | 0.95490 | 0.54770 | 0.0510* | |
H4B | 0.70710 | 0.99030 | 0.63570 | 0.0510* | |
H7A | 1.28910 | 0.79350 | 0.80580 | 0.0710* | |
H7B | 1.21960 | 0.70030 | 0.78420 | 0.0710* | |
H8A | 1.05210 | 0.71010 | 0.98730 | 0.1190* | |
H8B | 1.12810 | 0.80240 | 1.00990 | 0.1190* | |
H8C | 1.28800 | 0.72920 | 1.02950 | 0.1190* | |
H10 | 1.25300 | 0.94190 | 0.68690 | 0.0520* | |
H11 | 1.43330 | 1.04290 | 0.83030 | 0.0690* | |
H13 | 0.99860 | 1.04630 | 1.07380 | 0.0660* | |
H14 | 0.81950 | 0.94450 | 0.93710 | 0.0570* | |
H15 | 0.81240 | 0.34010 | 0.61080 | 0.0600* | |
H17 | 1.32490 | 0.47140 | 0.75080 | 0.0620* | |
H18 | 1.48340 | 0.34620 | 0.82400 | 0.0810* | |
H19 | 1.30090 | 0.22520 | 0.78890 | 0.0850* | |
H11W | 0.116 (17) | 0.672 (5) | 0.346 (13) | 0.08 (5)* | |
H12W | 0.086 (15) | 0.604 (7) | 0.456 (10) | 0.09 (6)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl1 | 0.086 (3) | 0.073 (3) | 0.080 (3) | −0.026 (3) | −0.014 (2) | −0.018 (3) |
N1 | 0.052 (7) | 0.025 (6) | 0.053 (7) | 0.011 (6) | −0.004 (6) | −0.003 (6) |
N2 | 0.059 (8) | 0.034 (7) | 0.098 (10) | 0.000 (6) | −0.024 (7) | −0.004 (7) |
N3 | 0.049 (7) | 0.031 (7) | 0.061 (7) | −0.004 (6) | −0.002 (6) | 0.002 (6) |
N4 | 0.034 (6) | 0.036 (6) | 0.053 (7) | 0.002 (5) | −0.008 (5) | −0.001 (5) |
C2 | 0.056 (10) | 0.032 (8) | 0.047 (8) | −0.007 (7) | −0.005 (7) | 0.008 (7) |
C4 | 0.041 (8) | 0.030 (8) | 0.034 (8) | 0.002 (6) | 0.014 (6) | 0.011 (6) |
C5 | 0.035 (7) | 0.019 (7) | 0.044 (8) | −0.008 (6) | 0.003 (6) | 0.008 (6) |
C6 | 0.041 (8) | 0.043 (8) | 0.033 (8) | −0.003 (7) | 0.003 (6) | 0.008 (7) |
C7 | 0.069 (10) | 0.053 (9) | 0.051 (9) | 0.002 (8) | −0.004 (7) | −0.001 (8) |
C8 | 0.080 (11) | 0.082 (11) | 0.063 (10) | 0.017 (9) | −0.031 (8) | −0.009 (9) |
C9 | 0.030 (7) | 0.033 (7) | 0.043 (8) | 0.004 (6) | 0.003 (6) | 0.009 (7) |
C10 | 0.040 (8) | 0.038 (8) | 0.056 (9) | −0.003 (6) | 0.017 (7) | −0.014 (7) |
C11 | 0.043 (9) | 0.058 (10) | 0.077 (11) | −0.034 (7) | 0.024 (8) | −0.018 (9) |
C12 | 0.036 (9) | 0.053 (9) | 0.058 (10) | 0.004 (7) | −0.013 (7) | −0.013 (8) |
C13 | 0.059 (11) | 0.066 (10) | 0.038 (8) | 0.008 (8) | 0.006 (8) | −0.001 (8) |
C14 | 0.059 (9) | 0.037 (8) | 0.050 (9) | −0.015 (7) | 0.017 (7) | −0.009 (7) |
O1 | 0.062 (7) | 0.039 (6) | 0.084 (7) | 0.004 (5) | −0.011 (5) | −0.004 (6) |
O2 | 0.061 (7) | 0.036 (5) | 0.083 (8) | −0.007 (5) | −0.004 (5) | −0.003 (6) |
N5 | 0.082 (10) | 0.048 (9) | 0.073 (9) | −0.009 (8) | 0.003 (7) | −0.002 (7) |
C15 | 0.066 (9) | 0.022 (7) | 0.063 (9) | 0.006 (7) | 0.010 (7) | 0.007 (8) |
C16 | 0.044 (8) | 0.031 (7) | 0.027 (6) | 0.006 (7) | 0.017 (6) | 0.006 (6) |
C17 | 0.049 (9) | 0.046 (9) | 0.055 (9) | −0.003 (8) | −0.005 (7) | −0.001 (8) |
C18 | 0.052 (9) | 0.075 (11) | 0.069 (10) | 0.027 (10) | −0.005 (7) | −0.001 (10) |
C19 | 0.104 (15) | 0.036 (9) | 0.076 (12) | 0.010 (10) | 0.025 (11) | 0.007 (9) |
C20 | 0.060 (11) | 0.049 (9) | 0.044 (9) | 0.008 (9) | −0.004 (8) | −0.004 (8) |
O1W | 0.056 (6) | 0.044 (6) | 0.104 (9) | −0.005 (6) | 0.013 (6) | 0.000 (7) |
Cl1—C12 | 1.765 (14) | C9—C14 | 1.380 (17) |
O1—C20 | 1.233 (17) | C10—C11 | 1.386 (18) |
O2—C20 | 1.267 (17) | C11—C12 | 1.36 (2) |
O1W—H11W | 0.97 (9) | C12—C13 | 1.332 (19) |
O1W—H12W | 0.96 (10) | C13—C14 | 1.374 (18) |
N1—C6 | 1.359 (16) | C7—H7A | 0.9693 |
N1—C2 | 1.361 (17) | C7—H7B | 0.9684 |
N2—C2 | 1.335 (16) | C8—H8A | 0.9577 |
N3—C4 | 1.328 (15) | C8—H8B | 0.9601 |
N3—C2 | 1.336 (16) | C8—H8C | 0.9616 |
N4—C4 | 1.328 (15) | C10—H10 | 0.9305 |
N1—H1 | 0.8597 | C11—H11 | 0.9329 |
N2—H2B | 0.8598 | C13—H13 | 0.9313 |
N2—H2A | 0.8599 | C14—H14 | 0.9299 |
N4—H4A | 0.8600 | C15—C16 | 1.416 (18) |
N4—H4B | 0.8597 | C16—C17 | 1.392 (17) |
N5—C15 | 1.314 (17) | C16—C20 | 1.527 (19) |
N5—C19 | 1.31 (2) | C17—C18 | 1.37 (2) |
C4—C5 | 1.434 (16) | C18—C19 | 1.37 (2) |
C5—C9 | 1.472 (16) | C15—H15 | 0.9322 |
C5—C6 | 1.346 (17) | C17—H17 | 0.9283 |
C6—C7 | 1.523 (18) | C18—H18 | 0.9297 |
C7—C8 | 1.533 (18) | C19—H19 | 0.9309 |
C9—C10 | 1.392 (16) | ||
H11W—O1W—H12W | 106 (10) | C8—C7—H7B | 109.47 |
C2—N1—C6 | 119.9 (10) | C6—C7—H7B | 109.38 |
C2—N3—C4 | 117.4 (11) | H7A—C7—H7B | 108.07 |
C2—N1—H1 | 120.04 | C6—C7—H7A | 109.39 |
C6—N1—H1 | 120.09 | C7—C8—H8B | 109.49 |
C2—N2—H2A | 120.09 | H8A—C8—H8B | 109.64 |
C2—N2—H2B | 119.91 | H8A—C8—H8C | 109.55 |
H2A—N2—H2B | 120.00 | H8B—C8—H8C | 109.31 |
H4A—N4—H4B | 120.00 | C7—C8—H8A | 109.55 |
C4—N4—H4B | 120.02 | C7—C8—H8C | 109.28 |
C4—N4—H4A | 119.98 | C9—C10—H10 | 119.45 |
C15—N5—C19 | 118.1 (12) | C11—C10—H10 | 119.50 |
N2—C2—N3 | 121.1 (12) | C12—C11—H11 | 120.42 |
N1—C2—N3 | 122.1 (11) | C10—C11—H11 | 120.38 |
N1—C2—N2 | 116.7 (11) | C12—C13—H13 | 119.99 |
N3—C4—N4 | 117.4 (10) | C14—C13—H13 | 119.66 |
N4—C4—C5 | 119.4 (10) | C13—C14—H14 | 119.34 |
N3—C4—C5 | 123.2 (10) | C9—C14—H14 | 119.32 |
C4—C5—C9 | 122.6 (10) | N5—C15—C16 | 123.6 (12) |
C4—C5—C6 | 115.7 (10) | C15—C16—C17 | 116.6 (12) |
C6—C5—C9 | 121.6 (10) | C15—C16—C20 | 120.6 (11) |
N1—C6—C7 | 113.0 (11) | C17—C16—C20 | 122.7 (12) |
C5—C6—C7 | 126.0 (11) | C16—C17—C18 | 118.7 (13) |
N1—C6—C5 | 121.0 (11) | C17—C18—C19 | 119.3 (13) |
C6—C7—C8 | 111.0 (10) | N5—C19—C18 | 123.7 (14) |
C5—C9—C14 | 120.7 (10) | O1—C20—O2 | 127.7 (13) |
C5—C9—C10 | 122.4 (11) | O2—C20—C16 | 113.5 (11) |
C10—C9—C14 | 116.8 (11) | O1—C20—C16 | 118.9 (12) |
C9—C10—C11 | 121.0 (11) | N5—C15—H15 | 118.26 |
C10—C11—C12 | 119.2 (12) | C16—C15—H15 | 118.15 |
Cl1—C12—C11 | 117.7 (10) | C18—C17—H17 | 120.80 |
C11—C12—C13 | 121.2 (13) | C16—C17—H17 | 120.51 |
Cl1—C12—C13 | 121.1 (11) | C17—C18—H18 | 120.27 |
C12—C13—C14 | 120.4 (13) | C19—C18—H18 | 120.46 |
C9—C14—C13 | 121.3 (12) | N5—C19—H19 | 118.31 |
C8—C7—H7A | 109.45 | C18—C19—H19 | 118.02 |
C6—N1—C2—N2 | −174.7 (11) | N1—C6—C7—C8 | −102.2 (13) |
C6—N1—C2—N3 | 6.0 (19) | C5—C6—C7—C8 | 77.6 (16) |
C2—N1—C6—C5 | −6.1 (17) | C5—C9—C14—C13 | 175.7 (11) |
C2—N1—C6—C7 | 173.7 (11) | C5—C9—C10—C11 | −175.1 (11) |
C4—N3—C2—N1 | 0.8 (18) | C10—C9—C14—C13 | −1.4 (18) |
C2—N3—C4—C5 | −7.5 (17) | C14—C9—C10—C11 | 2.0 (18) |
C2—N3—C4—N4 | 174.7 (11) | C9—C10—C11—C12 | −0.4 (19) |
C4—N3—C2—N2 | −178.5 (11) | C10—C11—C12—Cl1 | 176.1 (10) |
C15—N5—C19—C18 | −1 (2) | C10—C11—C12—C13 | −2 (2) |
C19—N5—C15—C16 | −1 (2) | C11—C12—C13—C14 | 3 (2) |
N3—C4—C5—C6 | 7.2 (17) | Cl1—C12—C13—C14 | −175.4 (10) |
N4—C4—C5—C9 | 7.5 (17) | C12—C13—C14—C9 | −1 (2) |
N3—C4—C5—C9 | −170.2 (11) | N5—C15—C16—C20 | −178.5 (12) |
N4—C4—C5—C6 | −175.1 (11) | N5—C15—C16—C17 | 3.8 (18) |
C4—C5—C9—C10 | −111.4 (13) | C15—C16—C17—C18 | −3.7 (17) |
C4—C5—C9—C14 | 71.6 (16) | C15—C16—C20—O2 | −173.8 (11) |
C9—C5—C6—C7 | −2.4 (19) | C17—C16—C20—O1 | −175.8 (11) |
C6—C5—C9—C10 | 71.3 (16) | C17—C16—C20—O2 | 3.8 (17) |
C6—C5—C9—C14 | −105.7 (14) | C20—C16—C17—C18 | 178.6 (11) |
C4—C5—C6—C7 | −179.9 (11) | C15—C16—C20—O1 | 6.6 (18) |
C9—C5—C6—N1 | 177.3 (11) | C16—C17—C18—C19 | 1.7 (19) |
C4—C5—C6—N1 | −0.1 (17) | C17—C18—C19—N5 | 1 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O2 | 0.86 | 1.83 | 2.686 (14) | 175 |
N2—H2A···O1W | 0.86 | 2.08 | 2.861 (15) | 150 |
N2—H2B···O1 | 0.86 | 2.10 | 2.957 (13) | 172 |
N4—H4A···O1i | 0.86 | 2.05 | 2.897 (14) | 168 |
N4—H4B···O1Wi | 0.86 | 2.26 | 3.031 (15) | 150 |
O1W—H11W···N5i | 0.97 (9) | 1.92 (9) | 2.862 (16) | 164 (10) |
O1W—H12W···O2ii | 0.96 (10) | 1.97 (10) | 2.862 (14) | 154 (9) |
Symmetry codes: (i) −x+1, y+1/2, −z+1; (ii) x−1, y, z. |
Experimental details
Crystal data | |
Chemical formula | C12H14ClN4+·C6H4NO2−·H2O |
Mr | 389.84 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 120 |
a, b, c (Å) | 6.570 (2), 16.055 (3), 9.480 (2) |
β (°) | 99.19 (3) |
V (Å3) | 987.1 (6) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.22 |
Crystal size (mm) | 0.23 × 0.20 × 0.18 |
Data collection | |
Diffractometer | Philips PW1100 |
Absorption correction | ψ scan (North et al., 1968) |
Tmin, Tmax | 0.951, 0.961 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 1909, 1807, 617 |
Rint | 0.059 |
(sin θ/λ)max (Å−1) | 0.595 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.056, 0.056, 0.85 |
No. of reflections | 1807 |
No. of parameters | 245 |
No. of restraints | 4 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.20, −0.25 |
Absolute structure | Flack (1983), no Friedel pairs |
Absolute structure parameter | 0.12 (14) |
Computer programs: PW1100 Software (Philips, 1978), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 2003).
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O2 | 0.86 | 1.83 | 2.686 (14) | 175 |
N2—H2A···O1W | 0.86 | 2.08 | 2.861 (15) | 150 |
N2—H2B···O1 | 0.86 | 2.10 | 2.957 (13) | 172 |
N4—H4A···O1i | 0.86 | 2.05 | 2.897 (14) | 168 |
N4—H4B···O1Wi | 0.86 | 2.26 | 3.031 (15) | 150 |
O1W—H11W···N5i | 0.97 (9) | 1.92 (9) | 2.862 (16) | 164 (10) |
O1W—H12W···O2ii | 0.96 (10) | 1.97 (10) | 2.862 (14) | 154 (9) |
Symmetry codes: (i) −x+1, y+1/2, −z+1; (ii) x−1, y, z. |
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Pyrimethamine [2,4-diamino-5-(p-chlorophenyl)-6-ethylpyrimidine] is an antifolate drug used in anti-malarial chemotherapy (Olliaro, 2001). The crystal structure of pyrimethamine (PMN) has been reported from our laboratory (Sethuraman & Muthiah, 2002) as have the structures of various protonated PMN salts (e.g. Devi et al., 2007). As part of these ongoing studies, the synthesis and structure of the title compound, (I), is now described.
The asymmetric unit of (I) contains a protonated pyrimethaminium (PMN) cation, nicotinate anion and a water molecule (Fig. 1). The PMN is protonated at N1 as it is evident from the enhancement of the C—N—C from 116.3 (2)° in neutral PMN molecule A and 116.09 (18)° in molecule B (Sethuraman & Muthiah, 2002) to 119.9 (10)° in (I). The dihedral angle between the 2,4-diamino pyrimidine and p-chlorophenyl rings is 70.3 (6)°. The torsion angle C5—C6—C7—C8, which represents the deviation of the ethyl group from the pyrimidine ring is 77.6 (16)°. The values are close to the results of modeling studies of DHFR-PMN complexes (Sansom et al., 1989). The C5—C9 bond length connecting the pyrimidine and phenyl ring in (I) is 1.472 (2) Å, in agreement with related structutres (De et al., 1989). The protonated N1 cation interacts with the carboxylate group of the nicotinate ion via N—H···O hydrogen bonds forming cyclic hydrogen bonded ring motif represented by graph-set notation R22(8) (Bernstein et al., 1995). The oxygen atom of the nicotinate anion bridges the 2-amino, 4-amino group of the PMN cation and water molecule forming a hydrogen bonded ring motif with graph-set notation R42(8). The frequently occurring R22(8) motif and R42(8) motif combine to form another motif, namely a DDA array (Fig. 2). Furthermore, the nicotinate anion and water molecule form a one dimensional supramolecular chain involving N—H···O and O—H···N hydrogen bonds (Fig. 3). π-π interactions between the aromatic rings are observed. The pyrimidine ring of PMN stacks with the nicotinate ring with a perpendicular separation of 3.551 Å, centroid-to-centroid distance of 3.637 (6) Å and a slip angle (the angle between the centroid-to-centroid vector and the normal to the plane) 19.05°.