Methyl 7-hydroxy-1,3-di­methyl-2,4-dioxo-1,2,3,4-tetra­hydro­pteridine-6-carboxyl­ate–di­methyl sulfoxide (1/1) forms chains containing O—H...O and C—H...O hydrogen bonds and aromatic π–π-stacking interactions

In the title compound, C₁₁H₁₂N₄O₅·C₂H₆OS, the molecular components are linked by a short hydrogen bond with dimensions O...O 2.517 (2) Å and O—H...O 168°. Paired C—H...O hydrogen bonds [C...O 3.362 (2) and 3.382 (2) Å; C—H...O 157 and 140°] generate cyclic centrosymmetric four-component aggregates reinforced by aromatic π–π-stacking interactions, and further C—H...O hydrogen bonds [C...O 3.472 (3) and 3.521 (2) Å; C—H...O 156 and 157°] link these aggregates into chains.

S1. Comment

Synthetic analogues of naturally occurring polyaza-heteroaromatic compounds, such as pteridines, are of considerable interest because of their extensive pharmaceutical potential, for example, as inhibitors of folic acid biosynthesis (Lang et al., 1995) and their action as antiallergic (Ferrand et al., 1996), antihelminthic (Ochoa et al., 1996), anti-inflammatory (Cottam et al., 1996) and antiviral agents (Molina et al., 1999). We report here the structure of one such synthetic pteridine, methyl 7-hydroxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropteridine-6-carboxylate, C₁₁H₁₂N₄O₅, (1), which is a useful intermediate for the synthesis of folic acid analogues (Molina et al., 1999) and which crystallizes from dimethyl sulfoxide (DMSO) solution as the monosolvate, i.e. (1)^.DMSO.

The bond lengths within the heteroaromatic portion of the molecule show clearly that form (1) carrying a hydroxyl group at position 7 is the correct representation, as opposed to the possible alternative tautomer (1a). In particular, the C7—O7 distance is very similar to the C62—O62 distance in the ester portion and much greater than the C2—O2 and C4—O4 distances; secondly, the bond lengths in the pyrazine portion of the heterocycle indicate considerable aromatic delocalization, with C—N distances consistently shorter than those in the pyrimidinedione portion. Moreover, the hydroxyl group O7—H7 forms a rather short and strong O—H···O hydrogen bond with O1 in the DMSO component as hydrogen-bond acceptor (Table 2), which could favour tautomer (1) over (1a). The non-H atoms in (1) are virtually coplanar, apart from those in the methoxycarbonyl fragment (Table 1). Overall, the bond lengths in the heterocyclic ring are similar to those in the unsubstituted pteridine-2,4-dione (2) (Norrestam et al., 1972) and in methylated pteridinediones in a variety of metal complexes retrieved from the Cambridge Structural Database (CSD; Allen & Kennard, 1993), exemplified by PUSJUI (Hueso-Ureña et al., 1998a), GAZTOQ, GAZZOW and GEBKUT (Hueso-Ureña et al., 1998b), and LIVJIJ (Hueso-Ureña et al., 1999).

The molecules of (1) and DMSO are linked by a series of hydrogen bonds (Table 2) into chains of fused centrosymmetric rings. In addition to the O—H···O hydrogen bond within the asymmetric unit (Fig. 1), there are C—H···O hydrogen bonds which link pairs of such units into centrosymmetric four-component aggregates: atoms C61 and C71 in the asymmetric unit at (x, y, z) act as donors, via H612 and H711, respectively, to O2 and O4, both at (-x, 2 - y, 1 - z), so generating a centrosymmetric dimer in which the two individual hydrogen bonds generate R²₂(18) and R⁴₄(24) rings, respectively (Fig. 2). The effect of these mutually reinforcing C—H···O hydrogen bonds is further enhanced by aromatic π–π-stacking interactions between the two heteroaromatic rings within this cyclic aggregate; the perpendicular distance between the two ring planes is ca 3.41 Å, and the centroid offset between the pyrazine ring in one pteridine and the pyrimidine ring in the other is only ca 0.46 Å giving almost perfect overlap.

The four-component cyclic aggregates are linked into chains by a further pair of C—H···O hydrogen bonds: C31 at (x, y, z) acts as donor, via H311, to O1 at (x, y, -1 + z), while C71 at (x, y, -1 + z) acts as donor, via H712, to O2 at (x, y, z), so generating an R²₂(9) motif (Fig. 3). These interactions serve to link the cyclic aggregates (Fig. 2) into chains running parallel to the [001] direction, in which the cyclic aggregates are centred at (0, 1, 0.5+n) (n = zero or integer) and the rings between them are centred at (0, 1, n) (n = zero or integer).

Related literature

For related literature, see: Allen & Kennard (1993); Cottam et al. (1996); Ferrand et al. (1996); Hueso-Ureña, Jiménez-Pulido, Moreno-Carretero, Quirós-Olazábal & Salas-Peregrín (1998a, 1998b, 1999); Lang et al. (1995); Molina et al. (1999); Norrestam et al. (1972); Ochoa et al. (1996).

S2. Experimental

A sample of (1) was prepared according to the published method of Molina et al. (1999). Crystals of (1)^.DMSO suitable for single-crystal X-ray diffraction were grown from a solution of (1) in DMSO.

S3. Refinement

The title compound crystallized in the triclinic system, and space group P1 was assumed and confirmed by the analysis. H atoms were treated as riding atoms, with C—H distances of 0.98 (CH₃) or 0.99 Å (CH₂), except for H7, whose position was located on a difference map and thereafter kept fixed.

Computing details

Data collection: KappaCCD Server Software (Nonius, 1997); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2001); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997) and PRPKAPPA (Ferguson, 1999).

Figures

	Fig. 1. The asymmetric unit of (1)^.DMSO showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. Part of the crystal structure of (1)^.DMSO showing the formation of a cyclic centrosymmetric four-component aggregate. The atoms marked with an asterisk (*) are at the symmetry position (-x, 2 - y, 1 - z). For clarity, the H atoms bonded to C11 and C31 have been omitted.
	Fig. 3. Part of the crystal structure of (1)^.DMSO showing formation of a [001] chain. For clarity, H atoms bonded to C11 and C61 have been omitted. Atoms marked with a hash (#) are at the symmetry position (x, y, -1 + z).

Methyl 7-hydroxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropteridine-6-carboxylate– dimethyl sulfoxide (1/1)

Crystal data

C11H12N4O5·C2H6OS	Z = 2
Mr = 358.37	F(000) = 376
Triclinic, P1	Dx = 1.457 Mg m^−3
a = 8.8926 (2) Å	Mo Kα radiation, λ = 0.71073 Å
b = 10.2539 (2) Å	Cell parameters from 3282 reflections
c = 10.8500 (4) Å	θ = 2.9–27.1°
α = 62.2233 (10)°	µ = 0.24 mm^−1
β = 82.4797 (10)°	T = 150 K
γ = 69.1050 (14)°	Lath, colourless
V = 817.03 (4) Å^3	0.25 × 0.10 × 0.10 mm

Data collection

KappaCCD diffractometer	3528 independent reflections
Radiation source: fine-focus sealed X-ray tube	2790 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.037
ϕ scans, and ω scans with κ offsets	θmax = 27.0°, θmin = 3.2°
Absorption correction: multi-scan (DENZO-SMN; Otwinowski & Minor, 1997)	h = −11→11
Tmin = 0.943, Tmax = 0.977	k = −13→13
7717 measured reflections	l = −13→13

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.045	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.121	H-atom parameters constrained
S = 1.05	w = 1/[σ^2(Fo^2) + (0.0602P)^2 + 0.1126P] where P = (Fo^2 + 2Fc^2)/3
3528 reflections	(Δ/σ)max = 0.001
222 parameters	Δρmax = 0.26 e Å^−3
0 restraints	Δρmin = −0.47 e Å^−3

Special details

Experimental. The program DENZO-SMN (Otwinowski & Minor, 1997) uses a scaling algorithm [Fox, G·C. & Holmes, K·C. (1966). Acta Cryst. 20, 886–891]which effectively corrects for absorption effects. High redundancy data were used in the scaling program hence the 'multi-scan' code word was used. No transmission coefficients are available from the program (only scale factors for each frame). The scale factors in the experimental table are calculated from the 'size' command in the SHELXL97 input file.

Geometry. Mean-plane data from the final SHELXL97 refinement run:-

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
N1	0.20984 (17)	0.78664 (15)	0.49222 (15)	0.0223 (3)
C11	0.2364 (2)	0.62775 (19)	0.6044 (2)	0.0315 (4)
C2	0.19117 (19)	0.81001 (19)	0.35871 (19)	0.0225 (4)
O2	0.19373 (15)	0.70316 (14)	0.33631 (14)	0.0311 (3)
N3	0.16521 (17)	0.96046 (16)	0.25231 (15)	0.0228 (3)
C31	0.1448 (2)	0.9872 (2)	0.1094 (2)	0.0312 (4)
C4	0.1674 (2)	1.08632 (19)	0.26898 (19)	0.0230 (4)
C4a	0.18943 (19)	1.05304 (18)	0.41223 (18)	0.0197 (4)
O4	0.14977 (17)	1.21352 (14)	0.16784 (13)	0.0344 (3)
N5	0.18648 (16)	1.17123 (15)	0.43783 (15)	0.0216 (3)
C6	0.20671 (19)	1.13969 (18)	0.56744 (18)	0.0203 (4)
C61	0.1968 (2)	1.26821 (19)	0.60216 (19)	0.0241 (4)
O61	0.47876 (16)	1.17528 (19)	0.65920 (17)	0.0440 (4)
C62	0.3422 (2)	1.23076 (19)	0.68481 (19)	0.0249 (4)
O62	0.30103 (14)	1.27098 (14)	0.78809 (13)	0.0270 (3)
C63	0.4326 (3)	1.2460 (2)	0.8712 (2)	0.0394 (5)
C7	0.2319 (2)	0.98491 (19)	0.67638 (18)	0.0215 (4)
O7	0.25198 (16)	0.95999 (14)	0.80495 (13)	0.0288 (3)
N8	0.23388 (17)	0.86859 (16)	0.65320 (15)	0.0220 (3)
C8a	0.21190 (19)	0.90451 (18)	0.51996 (18)	0.0190 (4)
S1	0.25987 (6)	0.54432 (5)	1.05050 (5)	0.02738 (16)
C71	0.0732 (2)	0.5694 (2)	1.1328 (2)	0.0313 (4)
C72	0.3856 (2)	0.4063 (2)	1.2018 (2)	0.0391 (5)
O1	0.29834 (17)	0.69205 (14)	1.00686 (13)	0.0348 (3)
H111	0.1554	0.5883	0.5948	0.047*
H112	0.2274	0.6293	0.6947	0.047*
H113	0.3442	0.5593	0.5987	0.047*
H311	0.1745	0.8864	0.1078	0.047*
H312	0.2142	1.0451	0.0482	0.047*
H313	0.0321	1.0482	0.0767	0.047*
H611	0.1847	1.3658	0.5145	0.029*
H612	0.0997	1.2871	0.6561	0.029*
H631	0.4952	1.1340	0.9178	0.059*
H632	0.3894	1.2830	0.9413	0.059*
H633	0.5023	1.3039	0.8107	0.059*
H7	0.2670	0.8445	0.8803	0.035*
H711	−0.0141	0.6436	1.0621	0.047*
H712	0.0746	0.6102	1.1981	0.047*
H713	0.0558	0.4684	1.1836	0.047*
H721	0.4984	0.3812	1.1759	0.059*
H722	0.3572	0.3108	1.2460	0.059*
H723	0.3709	0.4505	1.2672	0.059*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0283 (8)	0.0203 (7)	0.0226 (8)	−0.0112 (6)	0.0017 (6)	−0.0111 (6)
C11	0.0483 (12)	0.0204 (9)	0.0274 (11)	−0.0163 (8)	0.0001 (9)	−0.0082 (8)
C2	0.0200 (9)	0.0252 (8)	0.0273 (10)	−0.0091 (7)	0.0015 (7)	−0.0150 (8)
O2	0.0406 (8)	0.0296 (7)	0.0345 (8)	−0.0168 (6)	0.0033 (6)	−0.0204 (6)
N3	0.0257 (8)	0.0239 (7)	0.0220 (8)	−0.0077 (6)	−0.0024 (6)	−0.0127 (6)
C31	0.0385 (11)	0.0335 (10)	0.0263 (10)	−0.0093 (9)	−0.0037 (8)	−0.0180 (9)
C4	0.0244 (9)	0.0217 (8)	0.0243 (10)	−0.0075 (7)	−0.0014 (7)	−0.0110 (8)
C4a	0.0203 (8)	0.0197 (8)	0.0211 (9)	−0.0075 (7)	0.0000 (7)	−0.0099 (7)
O4	0.0549 (9)	0.0244 (7)	0.0222 (7)	−0.0137 (6)	−0.0056 (6)	−0.0073 (6)
N5	0.0225 (7)	0.0207 (7)	0.0234 (8)	−0.0085 (6)	0.0012 (6)	−0.0106 (6)
C6	0.0191 (8)	0.0201 (8)	0.0230 (9)	−0.0064 (7)	0.0005 (7)	−0.0107 (7)
C61	0.0281 (9)	0.0212 (8)	0.0258 (10)	−0.0082 (7)	0.0005 (7)	−0.0128 (7)
O61	0.0260 (8)	0.0636 (10)	0.0617 (11)	−0.0150 (7)	0.0093 (7)	−0.0457 (9)
C62	0.0288 (10)	0.0219 (8)	0.0297 (10)	−0.0123 (7)	0.0050 (8)	−0.0145 (8)
O62	0.0300 (7)	0.0289 (6)	0.0283 (7)	−0.0099 (5)	−0.0016 (5)	−0.0172 (6)
C63	0.0417 (12)	0.0438 (12)	0.0398 (13)	−0.0138 (10)	−0.0104 (9)	−0.0218 (10)
C7	0.0224 (8)	0.0237 (8)	0.0219 (9)	−0.0097 (7)	0.0037 (7)	−0.0124 (7)
O7	0.0462 (8)	0.0245 (6)	0.0192 (7)	−0.0150 (6)	0.0012 (6)	−0.0103 (5)
N8	0.0259 (8)	0.0221 (7)	0.0212 (8)	−0.0107 (6)	0.0020 (6)	−0.0106 (6)
C8a	0.0174 (8)	0.0212 (8)	0.0228 (9)	−0.0087 (7)	0.0025 (6)	−0.0122 (7)
S1	0.0375 (3)	0.0246 (2)	0.0236 (3)	−0.0140 (2)	0.00578 (19)	−0.0123 (2)
C71	0.0286 (10)	0.0290 (9)	0.0352 (11)	−0.0074 (8)	0.0011 (8)	−0.0153 (9)
C72	0.0287 (10)	0.0299 (10)	0.0411 (13)	−0.0105 (8)	0.0020 (9)	−0.0019 (9)
O1	0.0563 (9)	0.0267 (7)	0.0234 (7)	−0.0239 (6)	0.0003 (6)	−0.0054 (6)

Geometric parameters (Å, º)

N1—C2	1.376 (2)	C31—H311	0.9800
C2—N3	1.386 (2)	C31—H312	0.9800
N3—C4	1.391 (2)	C31—H313	0.9800
C4—C4a	1.452 (2)	C6—C61	1.502 (2)
N5—C4a	1.355 (2)	C61—C62	1.501 (2)
N5—C6	1.310 (2)	C61—H611	0.9900
C6—C7	1.426 (2)	C61—H612	0.9900
C7—N8	1.323 (2)	O62—C63	1.447 (2)
N1—C8a	1.381 (2)	C63—H631	0.9800
N8—C8a	1.338 (2)	C63—H632	0.9800
C4a—C8a	1.382 (2)	C63—H633	0.9800
C2—O2	1.220 (2)	O7—H7	1.050
C4—O4	1.223 (2)	S1—O1	1.5148 (13)
C62—O61	1.200 (2)	S1—C72	1.770 (2)
C62—O62	1.332 (2)	S1—C71	1.7723 (19)
C7—O7	1.320 (2)	C71—H711	0.9800
N1—C11	1.464 (2)	C71—H712	0.9800
C11—H111	0.9800	C71—H713	0.9800
C11—H112	0.9800	C72—H721	0.9800
C11—H113	0.9800	C72—H722	0.9800
N3—C31	1.467 (2)	C72—H723	0.9800
C2—N1—C8a	122.15 (14)	C6—C61—H612	109.0
C2—N1—C11	116.88 (14)	H611—C61—H612	107.8
C8a—N1—C11	120.89 (15)	O61—C62—O62	124.12 (17)
N1—C11—H111	109.5	O61—C62—C61	124.41 (17)
N1—C11—H112	109.5	O62—C62—C61	111.45 (14)
H111—C11—H112	109.5	C62—O62—C63	116.13 (15)
N1—C11—H113	109.5	O62—C63—H631	109.5
H111—C11—H113	109.5	O62—C63—H632	109.5
H112—C11—H113	109.5	H631—C63—H632	109.5
O2—C2—N1	121.04 (16)	O62—C63—H633	109.5
O2—C2—N3	121.89 (17)	H631—C63—H633	109.5
N1—C2—N3	117.05 (14)	H632—C63—H633	109.5
C2—N3—C4	125.12 (15)	O7—C7—N8	119.82 (15)
C2—N3—C31	117.68 (14)	O7—C7—C6	117.48 (15)
C4—N3—C31	117.06 (14)	N8—C7—C6	122.70 (16)
N3—C31—H311	109.5	C7—O7—H7	113.6
N3—C31—H312	109.5	C7—N8—C8a	115.78 (15)
H311—C31—H312	109.5	N8—C8a—N1	117.35 (14)
N3—C31—H313	109.5	N8—C8a—C4a	122.67 (15)
H311—C31—H313	109.5	N1—C8a—C4a	119.97 (15)
H312—C31—H313	109.5	O1—S1—C72	103.63 (9)
O4—C4—N3	120.46 (16)	O1—S1—C71	106.23 (9)
O4—C4—C4a	124.74 (16)	C72—S1—C71	97.93 (9)
N3—C4—C4a	114.79 (14)	S1—C71—H711	109.5
N5—C4a—C8a	120.82 (16)	S1—C71—H712	109.5
N5—C4a—C4	118.42 (14)	H711—C71—H712	109.5
C8a—C4a—C4	120.76 (15)	S1—C71—H713	109.5
C6—N5—C4a	117.84 (14)	H711—C71—H713	109.5
N5—C6—C7	120.17 (15)	H712—C71—H713	109.5
N5—C6—C61	119.93 (15)	S1—C72—H721	109.5
C7—C6—C61	119.85 (15)	S1—C72—H722	109.5
C62—C61—C6	112.81 (14)	H721—C72—H722	109.5
C62—C61—H611	109.0	S1—C72—H723	109.5
C6—C61—H611	109.0	H721—C72—H723	109.5
C62—C61—H612	109.0	H722—C72—H723	109.5
C8a—N1—C2—O2	178.16 (15)	C6—C61—C62—O62	−137.11 (15)
C11—N1—C2—O2	1.4 (2)	C7—C6—C61—C62	55.9 (2)
C8a—N1—C2—N3	−3.5 (2)	N5—C6—C61—C62	−126.59 (17)
C11—N1—C2—N3	179.70 (14)	O61—C62—O62—C63	0.7 (3)
O2—C2—N3—C4	−177.14 (16)	C61—C62—O62—C63	−177.54 (15)
N1—C2—N3—C4	4.5 (2)	N5—C6—C7—O7	179.82 (14)
O2—C2—N3—C31	−1.6 (2)	C61—C6—C7—O7	−2.6 (2)
N1—C2—N3—C31	−179.91 (15)	N5—C6—C7—N8	−0.9 (3)
C2—N3—C4—O4	176.93 (15)	C61—C6—C7—N8	176.61 (15)
C31—N3—C4—O4	1.4 (2)	O7—C7—N8—C8a	179.73 (14)
C2—N3—C4—C4a	−3.9 (2)	C6—C7—N8—C8a	0.5 (2)
C31—N3—C4—C4a	−179.42 (14)	C7—N8—C8a—N1	−178.66 (14)
O4—C4—C4a—N5	1.8 (3)	C7—N8—C8a—C4a	0.4 (2)
N3—C4—C4a—N5	−177.41 (14)	C2—N1—C8a—N8	−178.73 (14)
O4—C4—C4a—C8a	−178.62 (16)	C11—N1—C8a—N8	−2.1 (2)
N3—C4—C4a—C8a	2.2 (2)	C2—N1—C8a—C4a	2.2 (2)
C8a—C4a—N5—C6	0.5 (2)	C11—N1—C8a—C4a	178.83 (15)
C4—C4a—N5—C6	−179.91 (14)	N5—C4a—C8a—N8	−0.9 (3)
C4a—N5—C6—C7	0.4 (2)	C4—C4a—C8a—N8	179.47 (15)
C4a—N5—C6—C61	−177.14 (14)	N5—C4a—C8a—N1	178.11 (14)
C6—C61—C62—O61	44.7 (2)	C4—C4a—C8a—N1	−1.5 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O7—H7···O1	1.05	1.48	2.517 (2)	168
C31—H311···O1^i	0.98	2.56	3.472 (3)	156
C61—H612···O2^ii	0.98	2.57	3.382 (2)	140
C71—H711···O4^ii	0.98	2.44	3.362 (2)	157
C71—H712···O2^iii	0.98	2.60	3.521 (2)	157

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