1,3,7-Trimethyl-2,4-dioxo-1,2,3,4-tetra­hydro­pteridine-6-carboxylic acid hemihydrate

In the title compound, C₁₀H₁₀N₄O₄·0.5H₂O, the two rings of the pteridine system are nearly coplanar [dihedral angle = 4.25 (9)°]. The atoms of the carboxyl group are also coplanar with the pteridine unit [r.m.s. deviation from the mean plane of the pteridine skeleton = 0.092 (2) Å]. In the crystal, the presence of the water molecule of crystallization (O atom site symmetry 2) leads to a hydrogen-bonding pattern different from the one shown by many carboxylic acid compounds (dimers formed through O—H...O hydrogen bonds between neighbouring carboxyl groups): in the present structure, the water mol­ecule, which lies on a binary axis, acts as a bridge between two mol­ecules, forming a hydrogen-bonded dimer. In addition to the hydrogen bonds, there are π–π ring stacking inter­actions involving the pyrimidine and pyrazine rings [centroid–centroid distance = 3.689 (1)Å], and two different pyrazine rings [centroid–centroid distance = 3.470 (1)Å]. Finally, there is a C—O...π contact involving a carboxyl­ate C—O and the pyrimidine ring with a short O...Cg distance of 2.738 (2) Å.

Key indicators

• Single-crystal X-ray study
• T = 120 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.055
• wR factor = 0.140
• Data-to-parameter ratio = 10.9

checkCIF/PLATON results

No syntax errors found



Alert level B
PLAT432_ALERT_2_B Short Inter X...Y Contact  O62    ..  C4A     ..       2.81 Ang.
PLAT919_ALERT_3_B Reflection(s) # Likely Affected by the Beamstop           1

Alert level C
DIFMX01_ALERT_2_C  The maximum difference density is > 0.1*ZMAX*0.75
            _refine_diff_density_max given =      0.651
            Test value =      0.600
DIFMX02_ALERT_1_C  The maximum difference density is > 0.1*ZMAX*0.75
            The relevant atom site should be identified.
PLAT097_ALERT_2_C Large Reported Max.  (Positive) Residual Density       0.65 eA-3
PLAT432_ALERT_2_C Short Inter X...Y Contact  O62    ..  C8A     ..       2.92 Ang.
PLAT432_ALERT_2_C Short Inter X...Y Contact  O62    ..  C4      ..       2.99 Ang.
PLAT041_ALERT_1_C Calc. and Reported SumFormula    Strings  Differ          ?
PLAT042_ALERT_1_C Calc. and Reported MoietyFormula Strings  Differ          ?
PLAT045_ALERT_1_C Calculated and Reported Z Differ by ............       0.50 Ratio

Alert level G
PLAT380_ALERT_4_G Check Incorrectly? Oriented X(sp2)-Methyl Moiety         C3

   0 ALERT level A = In general: serious problem
   2 ALERT level B = Potentially serious problem
   8 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   4 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   5 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 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

---

S1. Comment

The interest in the 6-substituted lumazine derivatives has been increased since new coordination position pathways and new chemical and biological properties are provided while keeping the similarity to natural pterines. In this article we describe a new pteridine derivative, the 6-carboxy-1,3,7-trimetillumazine (6-carboxy-1,3,7-trimethylpteridine-2,4(1H,3H)-dione), which crystallizes as hemihydrate. The two rings of the pteridine system are nearly coplanar (acute dihedral angle 4.25°). The atoms of carboxylic group are also coplanar with the pteridine moiety. The presence of the water molecule makes the hydrogen bond pattern different from the usual one in many carboxylic acid compounds: in the present structure the water molecule, which lies on a binary axis, acts like a bridge between two molecules, using its full ability for H-bond formation (Fig. 1, Table 1). In addition to the H-bonds, there are π-π ring stacking interactions which involves the pirimidine (x,y,z) and pyrazine (1/2-x, 3/2-y,-z) rings (Fig. 2). The perpendicular distances are 3.261 and 3.173 Å, the centroid-centroid separation is 3.689 Å, the dihedral angle between the planes concerned is 4.25 °. Another π-π interaction between the pyrazine ring portions at (x,y,z) and (1/2-x,3/2-y,-z) is observed. The parameters, in the same order as before mentioned, are 3.189 Å, 3.470 Å, 0.02 °, respectively, corresponding to a centroids offset of 1.368 Å. Also, there is an important C—O···π contact involving O62 and the pyrimidine ring in x, 1-y, z-1/2 with a distance between the O62 atom and the centroid of the ring of 2.738 (2) Å, a slipping angle between the O62-centroid vector and the normal to the ring of 11.4° and a C61—O62···centroid angle of 131.2 (1)° .

Related literature

The precursor 6-acetyl-1,3,7-trimethyllumazine (DLMAceM) was obtained according to literature methods, see: Kim et al. (1999). For the structural features of both free and complexed related pteridine derivatives, see for example: Jiménez-Pulido et al. (2008a,b, 2009).

S2. Experimental

The new carboxylate ligand was prepared from the oxidation of 6-acetyl-1,3,7-trimethyllumazine with HNO₃ (40%). This suspension was stirred at room temperature for 3 hours. The ligand was filtered off and isolated in high yield (75-80%). The pale-yellow solution was kept at room for several days, affording prismatic yellow crystals that were collected and used for X-ray diffraction studies.

(6-acetyl-1,3,7-trimethyllumazine (DLMAceM) was prepared by standard Timmis reaction between 6-amino-5-nitrosopyrimidines and 1,3-dicarbonylic derivatives by the method described by Kim et al.)

S3. Refinement

The H atoms attached to O61 and O1w were located in subsequents difference Fourier map and refined isotropically. Methyl hydrogens were fixed geometrically and treated as riding with U_iso=1.5U_eq(C).

Computing details

Data collection: COLLECT (Nonius, 1998); cell refinement: DIRAX/LSQ (Duisenberg, 1992); data reduction: EVALCCD (Duisenberg et al., 2003); program(s) used to solve structure: SHELXL97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Mercury (Macrae et al., 2006); software used to prepare material for publication: WinGX (Farrugia, 1999) and PLATON (Spek, 2009).

Figures

	Fig. 1. View of the H-bonds (light green broken lines) scheme for 6-carboxy-1,3,7-trimethyllumazine showing the atom labels. Thermal ellipsoids are drawn at the 50% probability level.
	Fig. 2. View along [100] of the molecular arrangement in the crystal.

1,3,7-Trimethyl-2,4-dioxo-1,2,3,4-tetrahydropteridine-6-carboxylic acid hemihydrate

Crystal data

C10H10N4O4·0.5H2O	F(000) = 1080
Mr = 259.23	Dx = 1.586 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 1970 reflections
a = 15.7328 (19) Å	θ = 2.2–25.3°
b = 11.5784 (16) Å	µ = 0.13 mm^−1
c = 12.4062 (18) Å	T = 120 K
β = 106.113 (10)°	Prism, light yellow
V = 2171.1 (5) Å^3	0.46 × 0.24 × 0.19 mm
Z = 8

Data collection

Nonius KappaCCD diffractometer	1970 independent reflections
Radiation source: fine-focus sealed tube	1493 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.038
CCD rotation images, thick slices scans	θmax = 25.3°, θmin = 2.2°
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	h = −18→18
Tmin = 0.944, Tmax = 0.976	k = −13→13
14172 measured reflections	l = −14→14

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.055	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.140	w = 1/[σ^2(Fo^2) + (0.0794P)^2 + 0.6244P] where P = (Fo^2 + 2Fc^2)/3
S = 1.21	(Δ/σ)max < 0.001
1970 reflections	Δρmax = 0.65 e Å^−3
180 parameters	Δρmin = −0.58 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0125 (14)

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 F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ > σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ 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 (Ų)

	x	y	z	Uiso*/Ueq
O1w	0.5000	0.75980 (19)	0.2500	0.0271 (5)
N1	0.16439 (11)	0.99057 (14)	−0.04043 (14)	0.0213 (4)
C2	0.22500 (13)	1.06607 (18)	−0.06308 (17)	0.0217 (5)
N3	0.31401 (11)	1.03800 (14)	−0.02157 (14)	0.0215 (4)
C4	0.34674 (13)	0.94797 (17)	0.04960 (16)	0.0201 (5)
C4A	0.27938 (13)	0.87743 (17)	0.07728 (15)	0.0181 (5)
N5	0.30569 (11)	0.79181 (13)	0.14868 (13)	0.0190 (4)
C6	0.24465 (13)	0.73144 (16)	0.17889 (16)	0.0201 (5)
C7	0.15435 (14)	0.75701 (17)	0.13777 (16)	0.0211 (5)
N8	0.12794 (11)	0.84253 (14)	0.06406 (13)	0.0209 (4)
C8A	0.18987 (13)	0.90176 (17)	0.03424 (15)	0.0189 (5)
C1	0.07098 (14)	1.0169 (2)	−0.09039 (18)	0.0294 (6)
O2	0.20238 (10)	1.15152 (13)	−0.11888 (12)	0.0303 (4)
C3	0.37550 (14)	1.11665 (19)	−0.05308 (19)	0.0289 (5)
O4	0.42558 (9)	0.92948 (12)	0.08549 (12)	0.0257 (4)
C61	0.28018 (14)	0.63747 (18)	0.26029 (17)	0.0246 (5)
O61	0.36742 (10)	0.63064 (13)	0.30013 (12)	0.0283 (4)
O62	0.23356 (10)	0.56896 (13)	0.28942 (13)	0.0362 (5)
C71	0.08347 (14)	0.69621 (18)	0.17313 (18)	0.0267 (5)
H1W	0.5284 (19)	0.809 (2)	0.305 (2)	0.065 (10)*
H1A	0.0366	0.9451	−0.1014	0.044*
H1B	0.0636	1.0550	−0.1630	0.044*
H1C	0.0501	1.0683	−0.0404	0.044*
H3A	0.4363	1.0901	−0.0197	0.043*
H3B	0.3684	1.1945	−0.0257	0.043*
H3C	0.3631	1.1182	−0.1350	0.043*
H61	0.398 (2)	0.694 (3)	0.273 (3)	0.068 (9)*
H71A	0.0264	0.7330	0.1379	0.040*
H71B	0.0958	0.7004	0.2549	0.040*
H71C	0.0814	0.6151	0.1499	0.040*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1w	0.0226 (11)	0.0273 (12)	0.0279 (12)	0.000	0.0013 (9)	0.000
N1	0.0182 (9)	0.0239 (9)	0.0210 (9)	0.0019 (7)	0.0040 (7)	0.0038 (7)
C2	0.0226 (11)	0.0241 (11)	0.0182 (10)	0.0020 (9)	0.0055 (8)	−0.0001 (9)
N3	0.0204 (9)	0.0235 (9)	0.0206 (9)	−0.0005 (7)	0.0059 (7)	0.0031 (7)
C4	0.0211 (11)	0.0217 (11)	0.0167 (10)	0.0000 (9)	0.0036 (8)	−0.0015 (8)
C4A	0.0205 (11)	0.0188 (10)	0.0153 (10)	0.0026 (8)	0.0056 (8)	−0.0013 (8)
N5	0.0212 (9)	0.0189 (9)	0.0168 (8)	0.0006 (7)	0.0053 (7)	−0.0021 (7)
C6	0.0230 (11)	0.0201 (11)	0.0181 (10)	−0.0025 (9)	0.0073 (8)	−0.0029 (8)
C7	0.0251 (11)	0.0213 (11)	0.0178 (10)	−0.0019 (9)	0.0073 (9)	−0.0048 (8)
N8	0.0198 (9)	0.0228 (9)	0.0208 (9)	−0.0002 (7)	0.0067 (7)	−0.0017 (7)
C8A	0.0216 (11)	0.0199 (11)	0.0152 (10)	0.0009 (8)	0.0053 (8)	−0.0040 (8)
C1	0.0193 (11)	0.0373 (13)	0.0296 (12)	0.0047 (10)	0.0037 (9)	0.0078 (10)
O2	0.0283 (9)	0.0298 (9)	0.0318 (9)	0.0052 (7)	0.0065 (7)	0.0114 (7)
C3	0.0242 (12)	0.0299 (12)	0.0332 (12)	−0.0037 (10)	0.0091 (10)	0.0082 (10)
O4	0.0168 (8)	0.0304 (8)	0.0288 (8)	0.0000 (6)	0.0047 (6)	0.0050 (6)
C61	0.0276 (12)	0.0251 (12)	0.0209 (11)	−0.0005 (9)	0.0064 (9)	0.0003 (9)
O61	0.0265 (8)	0.0282 (9)	0.0277 (8)	0.0026 (7)	0.0036 (7)	0.0056 (7)
O62	0.0352 (9)	0.0340 (9)	0.0391 (10)	−0.0040 (8)	0.0100 (8)	0.0148 (8)
C71	0.0234 (11)	0.0314 (12)	0.0265 (12)	−0.0048 (10)	0.0093 (9)	−0.0009 (9)

Geometric parameters (Å, º)

O1w—H1W	0.90 (3)	N1—C2	1.379 (3)
O4—C4	1.215 (2)	N1—C1	1.460 (3)
C4A—N5	1.317 (3)	O61—C61	1.326 (3)
C4A—C8A	1.389 (3)	O61—H61	0.98 (3)
C4A—C4	1.453 (3)	O62—C61	1.202 (3)
N8—C8A	1.325 (3)	C7—C71	1.484 (3)
N8—C7	1.334 (3)	C71—H71A	0.9800
N5—C6	1.323 (3)	C71—H71B	0.9800
N3—C4	1.371 (3)	C71—H71C	0.9800
N3—C2	1.390 (3)	C3—H3A	0.9800
N3—C3	1.459 (3)	C3—H3B	0.9800
O2—C2	1.203 (2)	C3—H3C	0.9800
C8A—N1	1.367 (3)	C1—H1A	0.9800
C6—C7	1.401 (3)	C1—H1B	0.9800
C6—C61	1.484 (3)	C1—H1C	0.9800
N5—C4A—C8A	120.46 (18)	O2—C2—N1	121.85 (19)
N5—C4A—C4	117.93 (18)	O2—C2—N3	120.80 (18)
C8A—C4A—C4	121.56 (18)	N1—C2—N3	117.32 (17)
C8A—N8—C7	117.54 (18)	C7—C71—H71A	109.5
C4A—N5—C6	118.07 (18)	C7—C71—H71B	109.5
C4—N3—C2	125.18 (17)	H71A—C71—H71B	109.5
C4—N3—C3	119.27 (17)	C7—C71—H71C	109.5
C2—N3—C3	115.45 (16)	H71A—C71—H71C	109.5
N8—C8A—N1	118.56 (18)	H71B—C71—H71C	109.5
N8—C8A—C4A	122.21 (18)	N3—C3—H3A	109.5
N1—C8A—C4A	119.22 (18)	N3—C3—H3B	109.5
N5—C6—C7	121.83 (18)	H3A—C3—H3B	109.5
N5—C6—C61	114.46 (18)	N3—C3—H3C	109.5
C7—C6—C61	123.70 (18)	H3A—C3—H3C	109.5
C8A—N1—C2	121.70 (17)	H3B—C3—H3C	109.5
C8A—N1—C1	121.06 (17)	O62—C61—O61	120.23 (19)
C2—N1—C1	116.92 (17)	O62—C61—C6	122.8 (2)
C61—O61—H61	112.3 (17)	O61—C61—C6	116.92 (18)
O4—C4—N3	122.20 (18)	N1—C1—H1A	109.5
O4—C4—C4A	123.50 (18)	N1—C1—H1B	109.5
N3—C4—C4A	114.30 (17)	H1A—C1—H1B	109.5
N8—C7—C6	119.86 (18)	N1—C1—H1C	109.5
N8—C7—C71	115.99 (19)	H1A—C1—H1C	109.5
C6—C7—C71	124.13 (18)	H1B—C1—H1C	109.5

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1w—H1w···O4^i	0.91 (2)	1.94 (2)	2.841 (2)	172 (3)
O1w—H1w···N5^i	0.91 (2)	2.52 (3)	2.988 (2)	113 (2)
O61—H61···O1w	0.99 (3)	1.87 (3)	2.774 (2)	151 (3)
O61—H61···N5	0.99 (3)	2.13 (4)	2.635 (2)	110 (2)

Symmetry code: (i) −x+1, y, −z+1/2.