2-Cyano-N-(4,6-dimeth­oxy­pyrimidin-2-yl)acetamide: complex sheets built from N-H...O and C-H...O hydrogen bonds

Mol­ecules of the title compound, C₉H₁₀N₄O₃, (I), are linked into complex sheets by a combination of one N-H...O hydrogen bond and two C-H...O hydrogen bonds. Comparisons are drawn between (I) and some related compounds in respect of both their mol­ecular conformations and their hydrogen-bonding arrangements.

S1. Comment

We report here the molecular and supramolecular structure of the title compound, (I), (Fig. 1) which we compare with those of the related compounds, (II)–(V) (Low et al., 2002; Quesada et al., 2002, 2004), the isomeric compound, (VI), and the monosulfur analogue, (VII) (Trilleras et al., 2008). Pyrido[2,3-d]pyrimidines are attractive fused heterocyclic compounds from the biological and medical point of view. In an attempt to prepare novel intermediates for the synthesis of 7-aryl-6-cyanopyrido[2,3-d]pyrimidin-5-ones, we isolated (I) instead of the expected 5-cyanoacetylpyrimidine in a cyanoacetylation reaction from 2-amino-4,6-dimethoxypyrimidine (Quiroga et al., 2009).

The molecule of (I) is very nearly planar, as indicated by the key torsion angles (Table 1). The molecule could, in principle, exhibit exact mirror symmetry, with all of the non-H atoms lying on a crystallographic mirror plane. In fact, while the pyrimidine ring is planar within experimental uncertainty, with maximum deviations from the mean plane through the ring atoms of only 0.004 (2) Å for atoms N3 and C4, most of the exocyclic atoms are slightly displaced from this plane. The maximum displacements are those for atoms O22 [0.234 (2) Å] and C23 [0.269 (2) Å], displaced to opposite sides of the pyrimidine ring plane. These displacements are sufficient to preclude any possibility of imposed mirror symmetry. The bond distances and interbond angles present no unexpected values.

The molecular conformation, in which both of the methoxy C atoms are directed away from the ring C—H bond (Fig. 1), is in sharp contrast to that found in the related compounds (II) (Low et al., 2002), (III) (Quesada et al., 2002) and (IV) (Low et al., 2002), where only one of the alkoxy groups is directed away from the pyrimidine ring C—H bond, although in (V) (Quesada et al., 2004), the alkoxy groups adopt a conformation similar to that in (I). One plausible interpretation of these differences might be in terms of the direction-specific intermolecular interactions, specifically the intermolecular hydrogen bonds. However, there appears to be no obvious pattern connecting the hydrogen-bonding arrangements in these compounds with the molecular conformations. Thus, only one of the alkoxy O atoms is utilized as a hydrogen-bond acceptor in (I) (see below). In (II), neither of the O atoms is used but both ring N atoms act as hydrogen-bond acceptors. Compound (III) uses one O atom and the less-hindered of the ring N atoms as acceptors. Compound (IV) uses neither of the O atoms, just the less-hindered ring N atom. In (V), which crystallizes with Z' = 3, all six of the pyridyl N atoms act as hydrogen-bond acceptors but the O atoms and the ring N atoms play no part in the hydrogen bonding.

The molecules of (I) are linked into sheets by a combination of one N—H···O and two C—H···O hydrogen bonds (Table 2). Although there are three O atoms in the molecule of (I) potentially available as hydrogen-bond acceptors, methoxy atom O61 in fact plays no part in the hydrogen bonding; instead, amidic atom O22 acts as a double acceptor of hydrogen bonds. Neither of the ring N atoms acts as a hydrogen-bond acceptor, as access to these sites is effectively prevented by the adjacent methyl groups, along with the H atoms on atom C23 in the case of access to ring atom N3 (Fig. 1).

Two nearly linear hydrogen bonds, with atoms N21 and C5 as the donor atoms, link the molecules of (I) into a chain running parallel to the [211] direction and containing two independent types of centrosymmetric R²₂(8) ring (Bernstein et al., 1995). The rings containing inversion-related pairs of N—H···O hydrogen bonds are centred at (2n, 1/2 - n, 1/2 - n), where n represents an integer, and these alternate with the rings containing inversion-related pairs of C—H···O hydrogen bonds which are centred at (1 + 2n, -n, -n), where n again represents an integer (Fig. 2). a second, weaker, C—H···O hydrogen bond, utilizing methylene atom C23 as donor, links chains related by translation along [100] into a complex sheet lying parallel to (011) (Fig. 3).

It is of interest briefly to compare the hydrogen-bonding arrangements in (II)–(V) with that found here for (I). Of (II)–(V), (IV) (Low et al., 2002) is closest to (I) in overall constitution, but the molecules of (IV) are simply linked into centrosymmetric R²₂(8) rings by pairs of inversion-related N—H···N hydrogen bonds; N—H···O and C—H···O interactions are absent from the structure of (IV). The only hydrogen bonds present in the structures of compounds (II) (Low et al., 2002) and (V) (Quesada et al., 2004) are again of N—H···N type, giving a chain containing two types of R²₂(8) ring in (II) and two distinct types of chain containing only R²₂(20) rings in (V), where Z' = 3. One type of chain, which contains only one type of molecule, is formed by inversion, while the other, containing two types of molecule, is generated by translation. The aggregation in (III) (Quesada et al., 2002) takes the form of a molecular ladder, where pairs of antiparallel C(6) chains built from N—H···O hydrogen bonds provide the uprights and R²₂(8) rings formed by pairs of N—H···N hydrogen bonds provide the rungs of the ladder.

Compound (VI) (Trilleras et al., 2008) is isomeric with (I), although of somewhat different chemical constitution. The molecules of (VI) are linked into centrosymmetric dimers by pairs of both N—H···N and N—H···O hydrogen bonds. More similar to (I) in overall constitution is compound (VII) (Trilleras et al., 2008), where the molecules are linked into simple C(6) chains by an N—H···N hydrogen bond, rather than by an N—H..O hydrogen bond as might perhaps have been expected.

S2. Experimental

2-Amino-4,6-dimethoxypyrimidine (1.9 mmol) was added to a solution of cyanoacetic acid (1.9 mmol) in acetic anhydride (2.5 ml) at 340 K, and the mixture was then heated at 360 K for 5 min. During this period 2-cyano-N-(4,6-dimethoxypyrimidin-2-yl)acetamide started to crystallize. After heating for 5 min the reaction mixture was allowed to cool to ambient temperature, and the solid product was collected by filtration, washed with ethanol and recrystallized from dimethylformamide–ethanol (1:1 v/v). Colourless crystals of (I) suitable for single-crystal X-ray diffraction were obtained by slow evaporation, at ambient temperature and in air, of a solution in dimethylsulfoxide (yield 74%, m.p. 573–575 K). MS (EI 70 eV), m/z (relative abundance, %): 222 (57, M⁺), 221 (42), 154 (100), 155 (30), 83 (43), 69 (74), 68 (71).

S3. Refinement

All H atoms were located in difference maps. They were then treated as riding in geometrically idealized positions, with C—H = 0.95 (pyrimidine), 0.98 (CH₃) or 0.99 Å (CH₂) and N—H 0.88 Å, and with U_iso(H) = kU_eq(C,N), where k = 1.5 for the methyl groups, which were permitted to rotate but not to tilt, and 1.2 for all other H atoms.

Computing details

Data collection: COLLECT (Nonius, 1999); cell refinement: DIRAX/LSQ (Duisenberg et al., 2000); data reduction: EVALCCD (Duisenberg et al., 2003); program(s) used to solve structure: SIR2004 (Burla et al., 2005); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures

	Fig. 1. The molecular structure of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. A stereoview of part of the crystal structure of (I), showing the formation of a hydrogen-bonded chain parallel to [211] and containing two different types of centrosymmetric R^22(8) ring. For the sake of clarity, H atoms not involved in the motifs shown have been omitted.
	Fig. 3. A stereoview of part of the crystal structure of (I), showing the formation of a hydrogen-bonded sheet parallel to (011). For the sake of clarity, methyl H atoms have been omitted.

2-Cyano-N-(4,6-dimethoxypyrimidin-2-yl)acetamide

Crystal data

C9H10N4O3	Z = 2
Mr = 222.21	F(000) = 232
Triclinic, P1	Dx = 1.464 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 4.1760 (6) Å	Cell parameters from 2325 reflections
b = 11.296 (2) Å	θ = 3.4–27.5°
c = 12.070 (3) Å	µ = 0.11 mm^−1
α = 116.929 (15)°	T = 120 K
β = 90.478 (13)°	Plate, colourless
γ = 95.767 (15)°	0.40 × 0.32 × 0.19 mm
V = 504.13 (18) Å^3

Data collection

Bruker Nonius KappaCCD area-detector diffractometer	2325 independent reflections
Radiation source: Bruker Nonius FR591 rotating anode	1564 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.050
Detector resolution: 9.091 pixels mm^-1	θmax = 27.5°, θmin = 3.4°
ϕ and ω scans	h = −5→5
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	k = −14→14
Tmin = 0.961, Tmax = 0.979	l = −15→15
12440 measured reflections

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)] = 0.058	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.163	H-atom parameters constrained
S = 1.10	w = 1/[σ^2(Fo^2) + (0.0639P)^2 + 0.5073P] where P = (Fo^2 + 2Fc^2)/3
2325 reflections	(Δ/σ)max = 0.001
147 parameters	Δρmax = 0.34 e Å^−3
0 restraints	Δρmin = −0.31 e Å^−3

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

	x	y	z	Uiso*/Ueq
N1	0.5465 (5)	0.3773 (2)	0.24882 (18)	0.0232 (5)
C2	0.4461 (6)	0.2993 (2)	0.3000 (2)	0.0221 (5)
N3	0.5053 (5)	0.17523 (19)	0.26691 (18)	0.0228 (5)
C4	0.6852 (6)	0.1246 (2)	0.1696 (2)	0.0234 (5)
C5	0.8071 (6)	0.1937 (2)	0.1079 (2)	0.0253 (5)
H5	0.9377	0.1559	0.0391	0.030*
C6	0.7264 (6)	0.3219 (2)	0.1530 (2)	0.0246 (5)
N21	0.2476 (5)	0.3594 (2)	0.39712 (18)	0.0224 (5)
H21	0.2078	0.4398	0.4107	0.027*
C22	0.1051 (6)	0.3162 (2)	0.4742 (2)	0.0220 (5)
O22	−0.0883 (4)	0.38088 (16)	0.54600 (15)	0.0255 (4)
C23	0.1928 (6)	0.1902 (3)	0.4747 (2)	0.0278 (6)
H23A	0.1494	0.1144	0.3903	0.033*
H23B	0.4256	0.2008	0.4979	0.033*
C24	0.0062 (6)	0.1624 (2)	0.5627 (2)	0.0270 (6)
N25	−0.1415 (6)	0.1386 (2)	0.6301 (2)	0.0351 (6)
O41	0.7527 (4)	−0.00101 (17)	0.12940 (16)	0.0287 (4)
C41	0.5930 (7)	−0.0778 (3)	0.1846 (2)	0.0306 (6)
H41A	0.6631	−0.0379	0.2730	0.046*
H41B	0.6477	−0.1698	0.1424	0.046*
H41C	0.3593	−0.0783	0.1761	0.046*
O61	0.8334 (4)	0.39282 (17)	0.09430 (16)	0.0302 (5)
C61	0.7600 (8)	0.5286 (3)	0.1461 (3)	0.0375 (7)
H61A	0.5263	0.5299	0.1515	0.056*
H61B	0.8373	0.5685	0.0927	0.056*
H61C	0.8665	0.5800	0.2296	0.056*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0254 (11)	0.0231 (11)	0.0221 (10)	0.0040 (8)	0.0037 (8)	0.0108 (9)
C2	0.0223 (12)	0.0224 (12)	0.0217 (11)	0.0029 (9)	0.0022 (9)	0.0099 (10)
N3	0.0227 (10)	0.0206 (10)	0.0234 (10)	0.0042 (8)	0.0029 (8)	0.0083 (8)
C4	0.0240 (12)	0.0205 (12)	0.0222 (12)	0.0033 (9)	0.0004 (10)	0.0067 (10)
C5	0.0258 (13)	0.0265 (13)	0.0207 (11)	0.0030 (10)	0.0056 (10)	0.0080 (10)
C6	0.0242 (12)	0.0268 (13)	0.0237 (12)	0.0005 (10)	0.0002 (10)	0.0129 (10)
N21	0.0249 (11)	0.0200 (10)	0.0247 (10)	0.0057 (8)	0.0070 (8)	0.0114 (8)
C22	0.0222 (12)	0.0202 (12)	0.0233 (12)	0.0013 (9)	−0.0002 (10)	0.0100 (10)
O22	0.0299 (9)	0.0213 (9)	0.0262 (9)	0.0055 (7)	0.0066 (7)	0.0110 (7)
C23	0.0274 (13)	0.0280 (13)	0.0349 (14)	0.0094 (10)	0.0085 (11)	0.0190 (11)
C24	0.0332 (14)	0.0195 (12)	0.0301 (13)	0.0071 (10)	0.0037 (11)	0.0119 (11)
N25	0.0423 (14)	0.0320 (13)	0.0377 (13)	0.0093 (10)	0.0110 (11)	0.0207 (11)
O41	0.0335 (10)	0.0220 (9)	0.0303 (9)	0.0064 (7)	0.0094 (8)	0.0109 (8)
C41	0.0385 (15)	0.0238 (13)	0.0325 (14)	0.0065 (11)	0.0071 (12)	0.0147 (11)
O61	0.0401 (11)	0.0265 (10)	0.0276 (9)	0.0042 (8)	0.0093 (8)	0.0152 (8)
C61	0.0550 (19)	0.0270 (14)	0.0350 (15)	0.0079 (13)	0.0143 (14)	0.0172 (12)

Geometric parameters (Å, º)

N1—C6	1.322 (3)	C22—C23	1.508 (3)
N1—C2	1.326 (3)	C23—C24	1.449 (4)
C2—N3	1.322 (3)	C23—H23A	0.9900
C2—N21	1.389 (3)	C23—H23B	0.9900
N3—C4	1.328 (3)	C24—N25	1.135 (3)
C4—O41	1.337 (3)	O41—C41	1.434 (3)
C4—C5	1.369 (3)	C41—H41A	0.9800
C5—C6	1.377 (3)	C41—H41B	0.9800
C5—H5	0.9500	C41—H41C	0.9800
C6—O61	1.338 (3)	O61—C61	1.437 (3)
N21—C22	1.349 (3)	C61—H61A	0.9800
N21—H21	0.8800	C61—H61B	0.9800
C22—O22	1.222 (3)	C61—H61C	0.9800
C6—N1—C2	114.7 (2)	C24—C23—H23A	109.6
N3—C2—N1	127.9 (2)	C22—C23—H23A	109.6
N3—C2—N21	119.2 (2)	C24—C23—H23B	109.6
N1—C2—N21	112.8 (2)	C22—C23—H23B	109.6
C2—N3—C4	114.7 (2)	H23A—C23—H23B	108.2
N3—C4—O41	118.3 (2)	N25—C24—C23	178.9 (3)
N3—C4—C5	123.9 (2)	C4—O41—C41	117.40 (19)
O41—C4—C5	117.8 (2)	O41—C41—H41A	109.5
C4—C5—C6	115.0 (2)	O41—C41—H41B	109.5
C4—C5—H5	122.5	H41A—C41—H41B	109.5
C6—C5—H5	122.5	O41—C41—H41C	109.5
N1—C6—O61	118.7 (2)	H41A—C41—H41C	109.5
N1—C6—C5	123.8 (2)	H41B—C41—H41C	109.5
O61—C6—C5	117.5 (2)	C6—O61—C61	116.72 (19)
C22—N21—C2	131.3 (2)	O61—C61—H61A	109.5
C22—N21—H21	114.3	O61—C61—H61B	109.5
C2—N21—H21	114.3	H61A—C61—H61B	109.5
O22—C22—N21	120.2 (2)	O61—C61—H61C	109.5
O22—C22—C23	119.9 (2)	H61A—C61—H61C	109.5
N21—C22—C23	119.9 (2)	H61B—C61—H61C	109.5
C24—C23—C22	110.1 (2)
C6—N1—C2—N3	0.2 (4)	C4—C5—C6—O61	−178.6 (2)
C6—N1—C2—N21	−177.6 (2)	N3—C2—N21—C22	4.1 (4)
N1—C2—N3—C4	−0.6 (4)	N1—C2—N21—C22	−178.0 (2)
N21—C2—N3—C4	177.0 (2)	C2—N21—C22—O22	−172.6 (2)
C2—N3—C4—O41	−179.2 (2)	C2—N21—C22—C23	9.4 (4)
C2—N3—C4—C5	1.0 (3)	O22—C22—C23—C24	3.0 (3)
N3—C4—C5—C6	−0.8 (4)	N21—C22—C23—C24	−179.0 (2)
O41—C4—C5—C6	179.4 (2)	N3—C4—O41—C41	7.5 (3)
C2—N1—C6—O61	178.9 (2)	C5—C4—O41—C41	−172.7 (2)
C2—N1—C6—C5	0.0 (3)	N1—C6—O61—C61	4.0 (3)
C4—C5—C6—N1	0.3 (4)	C5—C6—O61—C61	−177.1 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N21—H21···O22^i	0.88	1.97	2.845 (3)	174
C5—H5···O41^ii	0.95	2.48	3.401 (3)	164
C23—H23B···O22^iii	0.99	2.58	3.372 (3)	137

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