Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807038342/lw2025sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807038342/lw2025Isup2.hkl |
CCDC reference: 660265
Key indicators
- Single-crystal X-ray study
- T = 293 K
- Mean (C-C) = 0.004 Å
- R factor = 0.049
- wR factor = 0.144
- Data-to-parameter ratio = 13.5
checkCIF/PLATON results
No syntax errors found
Alert level C PLAT250_ALERT_2_C Large U3/U1 Ratio for Average U(i,j) Tensor .... 2.26 PLAT420_ALERT_2_C D-H Without Acceptor N4 - H4B ... ? PLAT431_ALERT_2_C Short Inter HL..A Contact Cl1 .. O5 .. 3.06 Ang. PLAT790_ALERT_4_C Centre of Gravity not Within Unit Cell: Resd. # 2 C7 H3 N2 O6
Alert level G PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature 293 K PLAT200_ALERT_1_G Check the Reported _diffrn_ambient_temperature . 293 K
0 ALERT level A = In general: serious problem 0 ALERT level B = Potentially serious problem 4 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 3 ALERT type 2 Indicator that the structure model may be wrong or deficient 0 ALERT type 3 Indicator that the structure quality may be low 1 ALERT type 4 Improvement, methodology, query or suggestion 0 ALERT type 5 Informative message, check
A hot methanol solution of pyrimethamine (62 mg, Shah Pharma Chemicals., India) and an aqueous solution of 3,5-dinitrobenzoic acid (53 mg, Merck) were mixed in a 1:1 molar ratio and warmed for half an hour over a water bath. The product was then recrystallized from ethanol. After about a week, colourless crystals of (I) were obtained.
Methyl H atoms were placed in idealized positions, with Uiso(H)= 1.5Ueq(C). Other H atoms were placed in idealized positions, with C—H =0.97 (methylene) and 0.93 Å (aromatic), and N—H = 0.86 Å, and refined as riding on their carrier atoms, with Uiso(H) = 1.2Ueq (C, N).
Pyrimethamine [PMN] is an well known antifolate drug used in the treatment of malaria. In the chemotheraphy of malaria and neoplastic diseases, substituted 2,4-diaminopyrimidines are widely employed as metabolic inhibitors of pathways leading to the synthesis of proteins and nucleic acid (Hitchings & Burchall, 1965). The crystal structures of PMN (Sethuraman & Muthiah, 2002) and some of its complexes such as PMN hydrogen succinate, PMN hydrogen maleate, PMN hydrogen phthalate and PMN fumarate (Sethuraman et al., 2003), and PMN hydrogen glutarate and PMN formate (Stanley et al., 2002) have been reported from our laboratory. Most of the supramolecular crystals originate from strong N—H···O and O—H···N hydrogen bonds; the weak C—H···O bonds are known to play a significant role in determining the molecular packing of organic solids (Taylor & Kennard,1982). The present study has been undertaken to study the hydrogen bonding patterns involved in aminopyrimidine-carboxylate interactions.
The asymmetric unit of (I) contains a protonated PMN cation and a 3,5-dintrobenzoate anion. PMN is protonated at N1, as evident from the increase in the internal angle at N1 from 116.25 (18)° in neutral PMN molecule A and 116.09 (18)° in molecule B (Sethuraman & Muthiah, 2002) to 121.5 (2)°. The key conformational features of the PMN cations are described by two angles. The first is the dihedral angle between the 2,4-diaminopyrimidine and the 4-chlorophenyl mean planes. The second is the torsion angle that represents the deviation of the ethyl group from the pyrimidine plane. The dihedral angle between the pyrimidine and benzene ring is 63.17 (13)° and the torsion angle C5—C6—C7—C8 is -100.3 (3)°. These values are close to those observed in modelling studies of dihydrofolate reductase-pyrimethamine complexes, which indicates that these angles play an important role in the proper docking of the drug molecule in the active site of the enzyme (Sansom et al., 1989). The bond connecting the pyrimidine ring and the C5—C9 benzene ring is 1.490 (4) Å in length (De et al., 1989). The PMN cation interacts with atoms O1 and O2 of the carboxylate group, forming a cyclic hydrogen-bonded R22(8) dimer (Lynch & Jones, 2004). Two such motifs, related by inversion, are hydrogen-bonded to give a complementary DDAA (D= donor in hydrogen bond, A=acceptor in hydrogen bond) array of quadruple hydrogen-bonding patterns, comprising fused R22(8), R42(8) and R22(8) motifs (Fig. 2). A similar type of interaction has been observed in pyrimethaminium 3-chlorobenzoate (Devi et al., 2006), PMN nitrobenzoate salts (Stanley et al., 2005) and in some TMP(trimethoprim) salts with oxy acids (Giuseppetti et al., 1984; Cody, 1984; Baskar Raj et al., 2002). Each DDAA array is flanked on either side by R22(14) ring through N—H···O hydrogen bonds involving 4-amino group and one of the oxygen (O3) atom of the 5-nitro group. Here, one of the hydrogen (H7B) atom of the methylene (–CH2) group interacts with O6 oxygen atom of the 6-nitro group through C—H···O hydrogen bonds. Two inversion related PMN cations (atoms C11 and C13) and 3,5-dinitro benzoate anions (O5 & O6) are connected through the weak C—H···O hydrogen bonds forming a 24 membered ring with graph-set notation R44(24) as shown in Fig. 3.
For related literature, see: Baskar et al. (2002); Cody (1984); De et al. (1989); Devi et al. (2006); Giuseppetti et al. (1984); Hitchings & Burchall (1965); Lynch & Jones (2004); Sansom et al. (1989); Sethuraman & Muthiah (2002); Sethuraman et al. (2003); Stanley et al. (2002, 2005); Taylor & Kennard (1982).
Data collection: XSCANS (Siemens, 1994); cell refinement: XSCANS; data reduction: XSCANS; 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.
C12H14ClN4+·C7H3N2O6− | F(000) = 952 |
Mr = 460.84 | Dx = 1.484 Mg m−3 |
Monoclinic, P21/c | Cu Kα radiation, λ = 1.54178 Å |
Hall symbol: -P 2ybc | Cell parameters from 45 reflections |
a = 13.034 (2) Å | θ = 3.4–70.2° |
b = 7.099 (2) Å | µ = 2.10 mm−1 |
c = 22.468 (3) Å | T = 293 K |
β = 97.11 (3)° | Prism, colourless |
V = 2062.9 (7) Å3 | 0.13 × 0.10 × 0.08 mm |
Z = 4 |
Siemens AED single-crystal diffractometer | Rint = 0.022 |
Radiation source: fine-focus sealed tube | θmax = 70.2°, θmin = 3.4° |
Graphite monochromator | h = −15→14 |
ω–2θ scans | k = −8→8 |
4017 measured reflections | l = −8→27 |
3922 independent reflections | 1 standard reflections every 100 reflections |
2350 reflections with I > 2σ(I) | intensity decay: none |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.049 | H-atom parameters constrained |
wR(F2) = 0.144 | w = 1/[σ2(Fo2) + (0.0787P)2], where P = (Fo2 + 2Fc2)/3 |
S = 0.91 | (Δ/σ)max < 0.001 |
3922 reflections | Δρmax = 0.23 e Å−3 |
291 parameters | Δρmin = −0.24 e Å−3 |
0 restraints | Extinction correction: SHELXL97, FC*=KFC[1+0.001XFC2Λ3/SIN(2Θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0010 (2) |
C12H14ClN4+·C7H3N2O6− | V = 2062.9 (7) Å3 |
Mr = 460.84 | Z = 4 |
Monoclinic, P21/c | Cu Kα radiation |
a = 13.034 (2) Å | µ = 2.10 mm−1 |
b = 7.099 (2) Å | T = 293 K |
c = 22.468 (3) Å | 0.13 × 0.10 × 0.08 mm |
β = 97.11 (3)° |
Siemens AED single-crystal diffractometer | Rint = 0.022 |
4017 measured reflections | 1 standard reflections every 100 reflections |
3922 independent reflections | intensity decay: none |
2350 reflections with I > 2σ(I) |
R[F2 > 2σ(F2)] = 0.049 | 0 restraints |
wR(F2) = 0.144 | H-atom parameters constrained |
S = 0.91 | Δρmax = 0.23 e Å−3 |
3922 reflections | Δρmin = −0.24 e Å−3 |
291 parameters |
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 | 0.52577 (7) | 0.23938 (13) | 0.45621 (4) | 0.0715 (3) | |
N1 | 0.10982 (16) | 0.1850 (3) | 0.15156 (9) | 0.0413 (7) | |
N2 | 0.06617 (19) | −0.0094 (3) | 0.07126 (10) | 0.0534 (8) | |
N3 | 0.19609 (18) | −0.1033 (3) | 0.14335 (10) | 0.0464 (7) | |
N4 | 0.3256 (2) | −0.1913 (4) | 0.21484 (12) | 0.0613 (9) | |
C2 | 0.1242 (2) | 0.0225 (4) | 0.12227 (12) | 0.0408 (8) | |
C4 | 0.2526 (2) | −0.0642 (4) | 0.19524 (12) | 0.0427 (8) | |
C5 | 0.2411 (2) | 0.1036 (4) | 0.22933 (12) | 0.0414 (8) | |
C6 | 0.1659 (2) | 0.2262 (4) | 0.20558 (11) | 0.0400 (8) | |
C7 | 0.1334 (2) | 0.4014 (4) | 0.23515 (13) | 0.0479 (9) | |
C8 | 0.0348 (3) | 0.3676 (5) | 0.26294 (16) | 0.0669 (12) | |
C9 | 0.3088 (2) | 0.1389 (4) | 0.28669 (12) | 0.0427 (8) | |
C10 | 0.3087 (2) | 0.0216 (4) | 0.33584 (12) | 0.0478 (9) | |
C11 | 0.3758 (2) | 0.0503 (4) | 0.38781 (13) | 0.0526 (10) | |
C12 | 0.4418 (2) | 0.2014 (4) | 0.39072 (13) | 0.0486 (9) | |
C13 | 0.4434 (2) | 0.3226 (5) | 0.34340 (14) | 0.0571 (10) | |
C14 | 0.3783 (2) | 0.2898 (4) | 0.29103 (13) | 0.0530 (10) | |
O1 | −0.02513 (18) | 0.4454 (3) | 0.10443 (9) | 0.0642 (8) | |
O2 | −0.06964 (17) | 0.2731 (3) | 0.02248 (9) | 0.0610 (7) | |
O3 | −0.3249 (2) | 0.5328 (3) | −0.13549 (10) | 0.0716 (9) | |
O4 | −0.4092 (2) | 0.7804 (4) | −0.11937 (11) | 0.0882 (10) | |
O5 | −0.3036 (2) | 1.1559 (4) | 0.05664 (12) | 0.0925 (10) | |
O6 | −0.1869 (2) | 1.0551 (3) | 0.12436 (10) | 0.0747 (9) | |
N5 | −0.3424 (2) | 0.6653 (3) | −0.10412 (11) | 0.0524 (8) | |
N6 | −0.2407 (2) | 1.0385 (3) | 0.07634 (11) | 0.0565 (9) | |
C15 | −0.1492 (2) | 0.5704 (4) | 0.02909 (12) | 0.0419 (8) | |
C16 | −0.2084 (2) | 0.5473 (4) | −0.02585 (12) | 0.0447 (8) | |
C17 | −0.2784 (2) | 0.6882 (4) | −0.04601 (12) | 0.0434 (8) | |
C18 | −0.2896 (2) | 0.8512 (4) | −0.01397 (13) | 0.0472 (9) | |
C19 | −0.2291 (2) | 0.8697 (4) | 0.03992 (12) | 0.0449 (9) | |
C20 | −0.1582 (2) | 0.7329 (4) | 0.06244 (12) | 0.0447 (9) | |
C21 | −0.0745 (2) | 0.4170 (4) | 0.05396 (13) | 0.0465 (9) | |
H1 | 0.06440 | 0.26430 | 0.13590 | 0.0500* | |
H2A | 0.07450 | −0.11090 | 0.05150 | 0.0640* | |
H2B | 0.01990 | 0.07110 | 0.05760 | 0.0640* | |
H4A | 0.33350 | −0.29080 | 0.19400 | 0.0740* | |
H4B | 0.36440 | −0.17310 | 0.24820 | 0.0740* | |
H7A | 0.12230 | 0.50170 | 0.20570 | 0.0580* | |
H7B | 0.18780 | 0.44070 | 0.26600 | 0.0580* | |
H8A | −0.02020 | 0.33660 | 0.23200 | 0.1000* | |
H8B | 0.01700 | 0.47950 | 0.28340 | 0.1000* | |
H8C | 0.04510 | 0.26540 | 0.29100 | 0.1000* | |
H10 | 0.26250 | −0.07880 | 0.33390 | 0.0570* | |
H11 | 0.37610 | −0.03150 | 0.42020 | 0.0630* | |
H13 | 0.48770 | 0.42570 | 0.34650 | 0.0690* | |
H14 | 0.38070 | 0.36910 | 0.25830 | 0.0640* | |
H16 | −0.20160 | 0.44010 | −0.04880 | 0.0540* | |
H18 | −0.33620 | 0.94450 | −0.02840 | 0.0570* | |
H20 | −0.11770 | 0.75000 | 0.09910 | 0.0540* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl1 | 0.0730 (5) | 0.0757 (6) | 0.0580 (5) | −0.0147 (4) | −0.0234 (4) | 0.0001 (4) |
N1 | 0.0449 (12) | 0.0360 (11) | 0.0410 (12) | 0.0058 (10) | −0.0025 (10) | −0.0030 (9) |
N2 | 0.0620 (15) | 0.0468 (13) | 0.0472 (14) | 0.0135 (12) | −0.0102 (11) | −0.0143 (11) |
N3 | 0.0486 (13) | 0.0410 (12) | 0.0474 (13) | 0.0063 (10) | −0.0030 (10) | −0.0056 (10) |
N4 | 0.0671 (17) | 0.0504 (14) | 0.0602 (16) | 0.0203 (13) | −0.0167 (13) | −0.0138 (12) |
C2 | 0.0446 (15) | 0.0371 (13) | 0.0395 (14) | 0.0022 (11) | −0.0001 (11) | −0.0038 (11) |
C4 | 0.0438 (15) | 0.0361 (13) | 0.0470 (15) | 0.0040 (11) | 0.0007 (12) | −0.0021 (12) |
C5 | 0.0466 (15) | 0.0348 (13) | 0.0418 (15) | 0.0002 (11) | 0.0010 (12) | −0.0011 (11) |
C6 | 0.0458 (14) | 0.0331 (13) | 0.0400 (14) | −0.0011 (11) | 0.0011 (11) | −0.0020 (11) |
C7 | 0.0567 (17) | 0.0392 (14) | 0.0453 (16) | 0.0036 (13) | −0.0042 (13) | −0.0081 (12) |
C8 | 0.076 (2) | 0.060 (2) | 0.066 (2) | 0.0129 (17) | 0.0143 (18) | −0.0121 (17) |
C9 | 0.0477 (16) | 0.0355 (13) | 0.0435 (15) | 0.0019 (11) | 0.0006 (12) | −0.0024 (12) |
C10 | 0.0515 (16) | 0.0379 (14) | 0.0523 (17) | −0.0101 (12) | −0.0005 (13) | 0.0029 (13) |
C11 | 0.0633 (19) | 0.0452 (16) | 0.0465 (16) | −0.0074 (14) | −0.0039 (14) | 0.0047 (13) |
C12 | 0.0464 (15) | 0.0517 (17) | 0.0444 (15) | −0.0011 (13) | −0.0078 (12) | −0.0056 (13) |
C13 | 0.0598 (19) | 0.0485 (16) | 0.0604 (19) | −0.0151 (14) | −0.0029 (15) | 0.0018 (15) |
C14 | 0.0619 (19) | 0.0443 (16) | 0.0505 (17) | −0.0084 (14) | −0.0024 (14) | 0.0097 (13) |
O1 | 0.0791 (15) | 0.0488 (12) | 0.0572 (13) | 0.0225 (11) | −0.0212 (11) | −0.0088 (10) |
O2 | 0.0760 (14) | 0.0493 (12) | 0.0528 (12) | 0.0239 (11) | −0.0115 (10) | −0.0122 (10) |
O3 | 0.0985 (18) | 0.0525 (13) | 0.0577 (13) | 0.0149 (13) | −0.0142 (12) | −0.0140 (11) |
O4 | 0.0986 (19) | 0.0760 (17) | 0.0780 (17) | 0.0400 (15) | −0.0369 (14) | −0.0123 (14) |
O5 | 0.117 (2) | 0.0597 (15) | 0.0901 (18) | 0.0453 (15) | −0.0292 (16) | −0.0253 (14) |
O6 | 0.115 (2) | 0.0535 (13) | 0.0500 (13) | 0.0183 (13) | −0.0120 (13) | −0.0116 (11) |
N5 | 0.0606 (15) | 0.0433 (13) | 0.0504 (14) | 0.0029 (12) | −0.0051 (12) | 0.0007 (12) |
N6 | 0.0746 (18) | 0.0415 (13) | 0.0516 (15) | 0.0112 (13) | 0.0004 (13) | −0.0069 (12) |
C15 | 0.0460 (15) | 0.0345 (13) | 0.0449 (15) | 0.0052 (11) | 0.0042 (12) | 0.0009 (11) |
C16 | 0.0517 (16) | 0.0368 (13) | 0.0454 (15) | 0.0049 (12) | 0.0054 (12) | −0.0009 (12) |
C17 | 0.0490 (15) | 0.0398 (14) | 0.0395 (14) | 0.0005 (12) | −0.0022 (12) | 0.0023 (12) |
C18 | 0.0551 (17) | 0.0360 (14) | 0.0497 (16) | 0.0086 (12) | 0.0034 (13) | 0.0014 (12) |
C19 | 0.0575 (17) | 0.0322 (13) | 0.0448 (15) | 0.0042 (12) | 0.0054 (13) | −0.0007 (12) |
C20 | 0.0519 (16) | 0.0378 (14) | 0.0429 (15) | 0.0022 (12) | 0.0002 (12) | −0.0001 (12) |
C21 | 0.0494 (16) | 0.0416 (15) | 0.0468 (16) | 0.0094 (12) | −0.0006 (13) | 0.0006 (13) |
Cl1—C12 | 1.743 (3) | C9—C10 | 1.383 (4) |
O1—C21 | 1.249 (4) | C9—C14 | 1.398 (4) |
O2—C21 | 1.249 (4) | C10—C11 | 1.385 (4) |
O3—N5 | 1.214 (3) | C11—C12 | 1.371 (4) |
O4—N5 | 1.212 (4) | C12—C13 | 1.370 (4) |
O5—N6 | 1.214 (4) | C13—C14 | 1.383 (4) |
O6—N6 | 1.218 (3) | C7—H7A | 0.9706 |
N1—C2 | 1.353 (4) | C7—H7B | 0.9692 |
N1—C6 | 1.369 (3) | C8—H8B | 0.9605 |
N2—C2 | 1.312 (4) | C8—H8C | 0.9596 |
N3—C4 | 1.329 (4) | C8—H8A | 0.9603 |
N3—C2 | 1.338 (4) | C10—H10 | 0.9306 |
N4—C4 | 1.345 (4) | C11—H11 | 0.9307 |
N1—H1 | 0.8600 | C13—H13 | 0.9295 |
N2—H2B | 0.8595 | C14—H14 | 0.9297 |
N2—H2A | 0.8602 | C15—C16 | 1.382 (4) |
N4—H4A | 0.8606 | C15—C20 | 1.388 (4) |
N4—H4B | 0.8605 | C15—C21 | 1.520 (4) |
N5—C17 | 1.469 (4) | C16—C17 | 1.391 (4) |
N6—C19 | 1.469 (4) | C17—C18 | 1.380 (4) |
C4—C5 | 1.434 (4) | C18—C19 | 1.367 (4) |
C5—C6 | 1.369 (4) | C19—C20 | 1.392 (4) |
C5—C9 | 1.490 (4) | C16—H16 | 0.9296 |
C6—C7 | 1.496 (4) | C18—H18 | 0.9295 |
C7—C8 | 1.516 (5) | C20—H20 | 0.9296 |
Cl1···C18i | 3.575 (3) | C19···C11viii | 3.493 (4) |
Cl1···O5ii | 3.057 (3) | C20···C11viii | 3.429 (4) |
Cl1···H18ii | 2.8703 | C20···N2x | 3.434 (4) |
O1···N1 | 2.678 (3) | C20···C10viii | 3.526 (4) |
O1···C7 | 3.390 (4) | C21···C21iv | 3.494 (4) |
O2···N2iii | 2.822 (3) | C2···H8Bi | 2.9896 |
O2···C15iv | 3.396 (4) | C6···H14 | 3.0740 |
O2···N2 | 2.806 (3) | C6···H8Bi | 2.9929 |
O2···N6v | 3.143 (3) | C8···H1 | 3.0177 |
O3···N4iii | 3.009 (4) | C8···H8Bi | 2.9927 |
O3···C6iv | 3.242 (4) | C9···H7B | 2.6669 |
O5···Cl1vi | 3.057 (3) | C9···H4B | 2.5167 |
O5···C11vii | 3.252 (4) | C10···H4B | 2.5824 |
O6···C7viii | 3.331 (4) | C14···H7B | 2.6988 |
O6···C8viii | 3.297 (4) | C21···H1 | 2.6490 |
O1···H1 | 1.8194 | C21···H2B | 2.7432 |
O1···H20 | 2.4719 | H1···O2 | 2.9065 |
O1···H7A | 2.8191 | H1···H2B | 2.2494 |
O2···H1 | 2.9065 | H1···C8 | 3.0177 |
O2···H16 | 2.4993 | H1···C21 | 2.6490 |
O2···H2Aiii | 2.0166 | H1···O1 | 1.8194 |
O2···H2B | 1.9527 | H1···H8A | 2.5944 |
O3···H16 | 2.4566 | H1···H7A | 2.3614 |
O3···H4Aiii | 2.1577 | H2A···O2iii | 2.0166 |
O3···H14iv | 2.8515 | H2B···O2 | 1.9527 |
O4···H13vi | 2.5479 | H2B···H1 | 2.2494 |
O4···H18 | 2.4410 | H2B···C21 | 2.7432 |
O5···H18 | 2.4254 | H4A···O3iii | 2.1577 |
O5···H11vii | 2.4920 | H4B···H10 | 2.5598 |
O6···H7Bviii | 2.5952 | H4B···C10 | 2.5824 |
O6···H20 | 2.4400 | H4B···C9 | 2.5167 |
O6···H8Bviii | 2.8898 | H7A···H1 | 2.3614 |
N1···O1 | 2.678 (3) | H7A···O1 | 2.8191 |
N2···O2iii | 2.822 (3) | H7B···C14 | 2.6988 |
N2···C20v | 3.434 (4) | H7B···H14 | 2.5918 |
N2···O2 | 2.806 (3) | H7B···O6i | 2.5952 |
N4···C13ix | 3.430 (4) | H7B···C9 | 2.6669 |
N4···O3iii | 3.009 (4) | H8A···N1 | 2.8381 |
N4···C10 | 3.142 (4) | H8A···H1 | 2.5944 |
N6···O2x | 3.143 (3) | H8A···H8Bi | 2.5596 |
N1···H8Bi | 2.7557 | H8B···N1viii | 2.7557 |
N1···H8A | 2.8381 | H8B···C8viii | 2.9927 |
C2···C18iv | 3.560 (4) | H8B···C2viii | 2.9896 |
C2···C17iv | 3.471 (4) | H8B···C6viii | 2.9929 |
C6···O3iv | 3.242 (4) | H8B···O6i | 2.8898 |
C7···C14 | 3.377 (4) | H8B···H8Aviii | 2.5596 |
C7···O1 | 3.390 (4) | H8C···H20i | 2.5350 |
C7···O6i | 3.331 (4) | H10···H4B | 2.5598 |
C8···O6i | 3.297 (4) | H11···O5xi | 2.4920 |
C10···C20i | 3.526 (4) | H13···O4ii | 2.5479 |
C10···N4 | 3.142 (4) | H14···H7B | 2.5918 |
C11···C20i | 3.429 (4) | H14···O3iv | 2.8515 |
C11···O5xi | 3.252 (4) | H14···C6 | 3.0740 |
C11···C19i | 3.493 (4) | H16···O2 | 2.4993 |
C12···C19i | 3.551 (4) | H16···O3 | 2.4566 |
C13···N4xii | 3.430 (4) | H18···O4 | 2.4410 |
C14···C7 | 3.377 (4) | H18···O5 | 2.4254 |
C15···O2iv | 3.396 (4) | H18···Cl1vi | 2.8703 |
C17···C2iv | 3.471 (4) | H20···O1 | 2.4719 |
C18···C2iv | 3.560 (4) | H20···O6 | 2.4400 |
C18···Cl1viii | 3.575 (3) | H20···H8Cviii | 2.5350 |
C19···C12viii | 3.551 (4) | ||
C2—N1—C6 | 121.5 (2) | C6—C7—H7A | 109.49 |
C2—N3—C4 | 117.3 (2) | C6—C7—H7B | 109.55 |
C2—N1—H1 | 119.28 | C8—C7—H7A | 109.54 |
C6—N1—H1 | 119.21 | H7A—C7—H7B | 108.09 |
C2—N2—H2A | 119.96 | H8B—C8—H8C | 109.47 |
C2—N2—H2B | 120.01 | C7—C8—H8B | 109.48 |
H2A—N2—H2B | 120.03 | C7—C8—H8A | 109.46 |
H4A—N4—H4B | 120.01 | H8A—C8—H8C | 109.48 |
C4—N4—H4A | 119.99 | C7—C8—H8C | 109.48 |
C4—N4—H4B | 120.00 | H8A—C8—H8B | 109.46 |
O3—N5—O4 | 122.6 (3) | C9—C10—H10 | 119.22 |
O3—N5—C17 | 118.4 (2) | C11—C10—H10 | 119.32 |
O4—N5—C17 | 119.1 (2) | C12—C11—H11 | 120.59 |
O5—N6—O6 | 123.1 (3) | C10—C11—H11 | 120.58 |
O6—N6—C19 | 119.0 (2) | C12—C13—H13 | 120.36 |
O5—N6—C19 | 117.9 (2) | C14—C13—H13 | 120.43 |
N1—C2—N3 | 122.0 (2) | C13—C14—H14 | 119.60 |
N2—C2—N3 | 119.8 (3) | C9—C14—H14 | 119.58 |
N1—C2—N2 | 118.2 (2) | C16—C15—C20 | 120.4 (3) |
N3—C4—C5 | 124.0 (2) | C16—C15—C21 | 120.3 (3) |
N3—C4—N4 | 116.1 (3) | C20—C15—C21 | 119.3 (2) |
N4—C4—C5 | 119.9 (2) | C15—C16—C17 | 118.5 (3) |
C6—C5—C9 | 123.3 (3) | N5—C17—C16 | 119.2 (2) |
C4—C5—C6 | 115.9 (2) | N5—C17—C18 | 118.1 (2) |
C4—C5—C9 | 120.8 (2) | C16—C17—C18 | 122.7 (3) |
C5—C6—C7 | 125.7 (2) | C17—C18—C19 | 117.1 (3) |
N1—C6—C7 | 115.0 (2) | N6—C19—C18 | 118.9 (2) |
N1—C6—C5 | 119.2 (2) | N6—C19—C20 | 118.4 (2) |
C6—C7—C8 | 110.6 (2) | C18—C19—C20 | 122.6 (3) |
C10—C9—C14 | 118.0 (3) | C15—C20—C19 | 118.7 (2) |
C5—C9—C10 | 122.0 (2) | O1—C21—O2 | 126.1 (3) |
C5—C9—C14 | 119.9 (2) | O1—C21—C15 | 116.9 (3) |
C9—C10—C11 | 121.5 (3) | O2—C21—C15 | 116.9 (2) |
C10—C11—C12 | 118.8 (3) | C15—C16—H16 | 120.76 |
Cl1—C12—C11 | 119.1 (2) | C17—C16—H16 | 120.77 |
Cl1—C12—C13 | 119.3 (2) | C17—C18—H18 | 121.49 |
C11—C12—C13 | 121.6 (3) | C19—C18—H18 | 121.39 |
C12—C13—C14 | 119.2 (3) | C15—C20—H20 | 120.67 |
C9—C14—C13 | 120.8 (3) | C19—C20—H20 | 120.64 |
C8—C7—H7B | 109.48 | ||
C6—N1—C2—N2 | 178.6 (2) | N1—C6—C7—C8 | 76.1 (3) |
C6—N1—C2—N3 | −2.3 (4) | C5—C6—C7—C8 | −100.3 (3) |
C2—N1—C6—C5 | 2.6 (4) | C14—C9—C10—C11 | −0.6 (4) |
C2—N1—C6—C7 | −174.0 (2) | C5—C9—C14—C13 | −178.6 (3) |
C4—N3—C2—N1 | 1.1 (4) | C5—C9—C10—C11 | 176.6 (3) |
C4—N3—C2—N2 | −179.9 (3) | C10—C9—C14—C13 | −1.3 (4) |
C2—N3—C4—N4 | −178.8 (2) | C9—C10—C11—C12 | 1.6 (4) |
C2—N3—C4—C5 | −0.2 (4) | C10—C11—C12—C13 | −0.6 (4) |
O4—N5—C17—C18 | −6.9 (4) | C10—C11—C12—Cl1 | 179.5 (2) |
O3—N5—C17—C16 | −7.2 (4) | C11—C12—C13—C14 | −1.2 (4) |
O3—N5—C17—C18 | 171.9 (3) | Cl1—C12—C13—C14 | 178.6 (2) |
O4—N5—C17—C16 | 174.0 (3) | C12—C13—C14—C9 | 2.2 (4) |
O6—N6—C19—C18 | 180.0 (3) | C20—C15—C16—C17 | −1.5 (4) |
O6—N6—C19—C20 | 1.3 (4) | C21—C15—C16—C17 | 177.8 (2) |
O5—N6—C19—C20 | −179.1 (3) | C16—C15—C20—C19 | 1.1 (4) |
O5—N6—C19—C18 | −0.5 (4) | C21—C15—C20—C19 | −178.1 (2) |
N4—C4—C5—C9 | −0.4 (4) | C16—C15—C21—O1 | −178.5 (3) |
N3—C4—C5—C9 | −178.9 (3) | C16—C15—C21—O2 | 0.3 (4) |
N4—C4—C5—C6 | 179.1 (3) | C20—C15—C21—O1 | 0.8 (4) |
N3—C4—C5—C6 | 0.6 (4) | C20—C15—C21—O2 | 179.6 (3) |
C4—C5—C9—C10 | −62.7 (4) | C15—C16—C17—N5 | −179.6 (2) |
C4—C5—C6—C7 | 174.5 (3) | C15—C16—C17—C18 | 1.3 (4) |
C9—C5—C6—N1 | 177.7 (2) | N5—C17—C18—C19 | −179.9 (2) |
C4—C5—C9—C14 | 114.5 (3) | C16—C17—C18—C19 | −0.7 (4) |
C6—C5—C9—C10 | 117.9 (3) | C17—C18—C19—N6 | −178.2 (2) |
C4—C5—C6—N1 | −1.7 (4) | C17—C18—C19—C20 | 0.4 (4) |
C6—C5—C9—C14 | −64.9 (4) | N6—C19—C20—C15 | 178.0 (2) |
C9—C5—C6—C7 | −6.0 (4) | C18—C19—C20—C15 | −0.6 (4) |
Symmetry codes: (i) −x, y−1/2, −z+1/2; (ii) x+1, −y+3/2, z+1/2; (iii) −x, −y, −z; (iv) −x, −y+1, −z; (v) x, y−1, z; (vi) x−1, −y+3/2, z−1/2; (vii) −x, y+3/2, −z+1/2; (viii) −x, y+1/2, −z+1/2; (ix) −x+1, y−1/2, −z+1/2; (x) x, y+1, z; (xi) −x, y−3/2, −z+1/2; (xii) −x+1, y+1/2, −z+1/2. |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O1 | 0.86 | 1.82 | 2.678 (3) | 176 |
N2—H2A···O2iii | 0.86 | 2.02 | 2.822 (3) | 156 |
N2—H2B···O2 | 0.86 | 1.95 | 2.806 (3) | 172 |
N4—H4A···O3iii | 0.86 | 2.16 | 3.009 (4) | 170 |
C7—H7B···O6i | 0.97 | 2.60 | 3.331 (4) | 133 |
C11—H11···O5xi | 0.93 | 2.49 | 3.252 (4) | 139 |
C13—H13···O4ii | 0.93 | 2.55 | 3.455 (4) | 165 |
Symmetry codes: (i) −x, y−1/2, −z+1/2; (ii) x+1, −y+3/2, z+1/2; (iii) −x, −y, −z; (xi) −x, y−3/2, −z+1/2. |
Experimental details
Crystal data | |
Chemical formula | C12H14ClN4+·C7H3N2O6− |
Mr | 460.84 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 293 |
a, b, c (Å) | 13.034 (2), 7.099 (2), 22.468 (3) |
β (°) | 97.11 (3) |
V (Å3) | 2062.9 (7) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 2.10 |
Crystal size (mm) | 0.13 × 0.10 × 0.08 |
Data collection | |
Diffractometer | Siemens AED single-crystal |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 4017, 3922, 2350 |
Rint | 0.022 |
(sin θ/λ)max (Å−1) | 0.610 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.049, 0.144, 0.91 |
No. of reflections | 3922 |
No. of parameters | 291 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.23, −0.24 |
Computer programs: XSCANS (Siemens, 1994), XSCANS, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 2003), PLATON.
Cl1—C12 | 1.743 (3) | N1—C6 | 1.369 (3) |
O1—C21 | 1.249 (4) | N2—C2 | 1.312 (4) |
O2—C21 | 1.249 (4) | N3—C4 | 1.329 (4) |
O3—N5 | 1.214 (3) | N3—C2 | 1.338 (4) |
O4—N5 | 1.212 (4) | N4—C4 | 1.345 (4) |
O5—N6 | 1.214 (4) | N5—C17 | 1.469 (4) |
O6—N6 | 1.218 (3) | N6—C19 | 1.469 (4) |
N1—C2 | 1.353 (4) | ||
C2—N1—C6 | 121.5 (2) | N4—C4—C5 | 119.9 (2) |
C2—N3—C4 | 117.3 (2) | N1—C6—C7 | 115.0 (2) |
O3—N5—O4 | 122.6 (3) | N1—C6—C5 | 119.2 (2) |
O3—N5—C17 | 118.4 (2) | Cl1—C12—C11 | 119.1 (2) |
O4—N5—C17 | 119.1 (2) | Cl1—C12—C13 | 119.3 (2) |
O5—N6—O6 | 123.1 (3) | N5—C17—C16 | 119.2 (2) |
O6—N6—C19 | 119.0 (2) | N5—C17—C18 | 118.1 (2) |
O5—N6—C19 | 117.9 (2) | N6—C19—C18 | 118.9 (2) |
N1—C2—N3 | 122.0 (2) | N6—C19—C20 | 118.4 (2) |
N2—C2—N3 | 119.8 (3) | O1—C21—O2 | 126.1 (3) |
N1—C2—N2 | 118.2 (2) | O1—C21—C15 | 116.9 (3) |
N3—C4—C5 | 124.0 (2) | O2—C21—C15 | 116.9 (2) |
N3—C4—N4 | 116.1 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O1 | 0.86 | 1.82 | 2.678 (3) | 176 |
N2—H2A···O2i | 0.86 | 2.02 | 2.822 (3) | 156 |
N2—H2B···O2 | 0.86 | 1.95 | 2.806 (3) | 172 |
N4—H4A···O3i | 0.86 | 2.16 | 3.009 (4) | 170 |
C7—H7B···O6ii | 0.97 | 2.60 | 3.331 (4) | 133 |
C11—H11···O5iii | 0.93 | 2.49 | 3.252 (4) | 139 |
C13—H13···O4iv | 0.93 | 2.55 | 3.455 (4) | 165 |
Symmetry codes: (i) −x, −y, −z; (ii) −x, y−1/2, −z+1/2; (iii) −x, y−3/2, −z+1/2; (iv) x+1, −y+3/2, z+1/2. |
Pyrimethamine [PMN] is an well known antifolate drug used in the treatment of malaria. In the chemotheraphy of malaria and neoplastic diseases, substituted 2,4-diaminopyrimidines are widely employed as metabolic inhibitors of pathways leading to the synthesis of proteins and nucleic acid (Hitchings & Burchall, 1965). The crystal structures of PMN (Sethuraman & Muthiah, 2002) and some of its complexes such as PMN hydrogen succinate, PMN hydrogen maleate, PMN hydrogen phthalate and PMN fumarate (Sethuraman et al., 2003), and PMN hydrogen glutarate and PMN formate (Stanley et al., 2002) have been reported from our laboratory. Most of the supramolecular crystals originate from strong N—H···O and O—H···N hydrogen bonds; the weak C—H···O bonds are known to play a significant role in determining the molecular packing of organic solids (Taylor & Kennard,1982). The present study has been undertaken to study the hydrogen bonding patterns involved in aminopyrimidine-carboxylate interactions.
The asymmetric unit of (I) contains a protonated PMN cation and a 3,5-dintrobenzoate anion. PMN is protonated at N1, as evident from the increase in the internal angle at N1 from 116.25 (18)° in neutral PMN molecule A and 116.09 (18)° in molecule B (Sethuraman & Muthiah, 2002) to 121.5 (2)°. The key conformational features of the PMN cations are described by two angles. The first is the dihedral angle between the 2,4-diaminopyrimidine and the 4-chlorophenyl mean planes. The second is the torsion angle that represents the deviation of the ethyl group from the pyrimidine plane. The dihedral angle between the pyrimidine and benzene ring is 63.17 (13)° and the torsion angle C5—C6—C7—C8 is -100.3 (3)°. These values are close to those observed in modelling studies of dihydrofolate reductase-pyrimethamine complexes, which indicates that these angles play an important role in the proper docking of the drug molecule in the active site of the enzyme (Sansom et al., 1989). The bond connecting the pyrimidine ring and the C5—C9 benzene ring is 1.490 (4) Å in length (De et al., 1989). The PMN cation interacts with atoms O1 and O2 of the carboxylate group, forming a cyclic hydrogen-bonded R22(8) dimer (Lynch & Jones, 2004). Two such motifs, related by inversion, are hydrogen-bonded to give a complementary DDAA (D= donor in hydrogen bond, A=acceptor in hydrogen bond) array of quadruple hydrogen-bonding patterns, comprising fused R22(8), R42(8) and R22(8) motifs (Fig. 2). A similar type of interaction has been observed in pyrimethaminium 3-chlorobenzoate (Devi et al., 2006), PMN nitrobenzoate salts (Stanley et al., 2005) and in some TMP(trimethoprim) salts with oxy acids (Giuseppetti et al., 1984; Cody, 1984; Baskar Raj et al., 2002). Each DDAA array is flanked on either side by R22(14) ring through N—H···O hydrogen bonds involving 4-amino group and one of the oxygen (O3) atom of the 5-nitro group. Here, one of the hydrogen (H7B) atom of the methylene (–CH2) group interacts with O6 oxygen atom of the 6-nitro group through C—H···O hydrogen bonds. Two inversion related PMN cations (atoms C11 and C13) and 3,5-dinitro benzoate anions (O5 & O6) are connected through the weak C—H···O hydrogen bonds forming a 24 membered ring with graph-set notation R44(24) as shown in Fig. 3.