Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270113020465/uk3079sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270113020465/uk3079Isup2.hkl |
CCDC reference: 964768
Pyrimidinones have attracted considerable attention in synthetic organic chemistry because of their wide range of biological activities (Kappe 2000), while multicomponent reactions are gaining importance in organic and medicinal chemistry because of their capacity to generate multifunctionalized products. We have now obtained the unexpected product 5,5'-methylenebis[6-amino-3-methyl-2-methylsulfanylpyrimidin-4(3H)-one], (I), from a reaction involving a 4-aminopyrimidin-6-one, paraformaldehyde and tetralone which was intended to produce the corresponding 6,9-dihydrobenzo[h]pyrimido[4,5-b]quinolin-8(5H)-one. In the event, the tetralone played no part in the reaction, which was a simple condensation between the pyrimidinone and paraformaldehyde, and the product (I) can, in fact, be prepared in satisfactory yield without the presence of tetralone. Methylendipyrimidinone derivatives such as (I) can be used as multifunctionalized precursors in the synthesis of more complex heterocyclic compounds.
A mixture of 6-amino-3-methyl-2-(methylsulfanyl)pyrimidin-4(3H)-one (1.0 mmol) and paraformaldehyde (5.0 mmol) in dimethylformamide (5.0 ml) was heated under reflux for 5 h, after which time the product started to crystallize. The mixture was allowed to cool to ambient temperature, and the resulting solid product was collected by filtration and washed with methanol. Orange crystals suitable for single-crystal X-ray diffraction were selected directly from the crystallized product [yield 70%, m.p. >573 K (decomposition)]. MS (70 eV) m/z (%): 354 (100, M+), 339 (28), 249 (57), 201 (16), 184 (55), 150 (19), 88 (83), 57 (18).
Crystal data, data collection and structure refinement details are summarized in Table 1. All H atoms were located in difference maps. H atoms bonded to C atoms were then treated as riding atoms in geometrically idealized positions, with C—H = 0.98 (CH3) or 0.99 Å (CH2) and Uiso(H) = kUeq(C), where k = 1.2 for the H atoms bonded to atom C51 and k = 1.5 for the methyl groups, which were permitted to rotate but not to tilt. The H atoms bonded to atom N61 were permitted to ride at the positions located in a difference map, with Uiso(H) = 1.2Ueq(N), giving the N—H distances shown in Table 2. The reflection 200, which had been badly attenuated by the beam-stop, was omitted from the data set.
The molecules of the title compound, (I) (Fig. 1), lie across twofold rotation axes in the space group C2/c, and the reference molecule was selected as one lying across the axis along (1/2, y, 1/4). The molecule of (I) contains two symmetry-related N—H···O hydrogen bonds (Table 2), which produce a pair of edge-fused S(8) rings (Bernstein et al., 1995) (Fig. 1). The intramolecular N—H···O hydrogen bond and the intermolecular N—H···O hydrogen bond, discussed below, have similar and fairly short N···O distances and in both the N—H···O unit deviates only slightly from linearity; accordingly, both hydrogen bonds can be regarded as fairly strong for their type. However, apart from the intermolecular hydrogen bond, there are no direction-specific intermolecular interactions in the crystal structure of (I).
Despite the high degree of substitution on the pyrimidine ring, this ring is effectively planar, with a maximum deviation from the mean plane of the six ring atoms of only 0.026 (2) Å for atom C5. This ring planarity is in marked contrast to the puckered rings often found for highly substituted pyrimidine rings, particularly for those carrying substituents at each of positions 4, 5 and 6 (Melguizo et al., 2003; Quesada et al., 2003, 2004; Low et al., 2007; Trilleras et al., 2007; Cobo et al., 2008). Indeed, with the exception of the central atom C51, discussed below, the maximum deviations of any of the substituent atoms from the mean plane of the pyrimidine ring are 0.060 (2) Å for atom N61 and 0.059 (1) Å for atom S21. Although atom S21 is almost coplanar with the ring, the adjacent atom C21 is displaced from the ring plane by 0.408 (2) Å, consistent with the torsion angles (Table 1) involving this atom.
A striking feature of the molecular geometry is the wide C—C—C angle at the central C51 atom (Table 2), although the C5—C51 distance is entirely typical of its type [mean value (Allen et al., 1987) = 1.510 Å and upper quartile value = 1.518 Å]. This angle is associated with a displacement of atom C51 from the mean plane of the ring by 0.213 (3) Å in the sense which gives a smaller C—C—C angle than would be the case of C51 were coplanar with the ring. By contrast, the central C—C—C angle in diphenylmethane, Ph2CH2, is entirely normal at 112.4 (7)° (Barnes et al., 1981), while the C—C—C angle in propane, determined on isolated molecules in the gas phase, is 112 (1)° (Iijima, 1972). While X—CH2—X bond angles which are significantly larger than the ideal tetrahedral value are uncommon, the value found here is not without precedent. For example, in methylenebis(1,3,5-trimethyl-4-imidazolin-2-one), (II) (see Scheme), which crystallizes with Z' = 2 (Glidewell et al., 1979), the central C—C—C angles in the two independent molecules are 113.1 (8) and 116.9 (8)°. However, if the substituent X is based upon an element from the second row of the Periodic Table, substantially larger X—CH2—X angles have been observed: thus, in CH2(PSePh2)2, the central P—C—P angle in 117.9 (6)° (Carroll & Titus, 1977) and in CH2(SiPh3)2, the central Si—C—Si angle is 128.8 (7)° (Glidewell & Liles, 1982). If the central –CH2– unit is replaced by one of its isoelectronic analogues, i.e. –NH– or –O–, similar behaviour is observed; thus, the C—O—C angle in O(CPh3)2 is 127.9 (1)° (Glidewell & Liles, 1978), while in HN(SiPh3)2, the central Si—N—Si angle is as large as 138.1 (4)° (Glidewell & Holden, 1981). All these observations, and others on similar compounds, are most straightforwardly interpreted in terms of steric repulsions between the substituents dominated, but not exclusively controlled, by the nonbonded contacts between the α-atoms denoted as X above.
Anomalously large C—C—C angles have also been reported at the bridging methine C atom in compound (III) (see Scheme), where the C—C—C angle at the bridging C atom is 127.8 (3)° (Insuasty et al., 2012) and in compounds (IV)–(X), where the corresponding angles are all close to 130° (Delgado et al., 2005, 2006). In (III), there is a short and repulsive intramolecular N···S contact, with a similar C—H···S contact in each of (IV)–(X). The surprising feature in all of these molecules is the effective planarity of their molecular skeletons. Rather than using a rotation of the imidazole or aryl ring about the single bond linking it to the bridging atom, which might intuitively seem to be least energetic pathway, the steric stress is instead relieved in every case by an expansion of the central C—C—C angle.
The structural metrics of simple molecular systems characterized by bond angles which are significantly larger than those expected from the VSEPR (valence shell electron pair repulsion) model (Gillespie & Nyholm, 1957; Gillespie, 1972) have been successfully analysed in steric terms (Bartell, 1960; Burdett, 1980) by recognizing that, for geometrical purposes, atoms within molecules can be treated as hard incompressible entities (Bartell, 1960), which do not, however behave as spherical objects, as judged by the angular variation of the limiting contact distances in molecular crystals (Nyburg & Faerman, 1985). In the present compound, (I), there are no other direction-specific interactions between the molecules, as noted above, and the mutual disposition and orientation of the two pyrimidine rings appears to be controlled by the hydrogen bonds. Accordingly, the steric strain around atom C51 can be relieved by three plausible means, or by some combination of them: (i) the C5—C51 bond length could become perturbed from its normal value, although this is probably the most energy-expensive option; (ii) the C5—C51—C5i angle [symmetry code: (i) -x+1, y, -z+1/2] could be widened; or (iii) atom C51 could be displaced from the plane of the pyrimidine ring. Since the C5—C51 bond is of normal length, this leaves a combination of angle enlargement and atom displacement available for the relief of steric strain. Given the separation of atoms C5 and C5i, confining atom C51 to the plane of the pyrimidine ring would require a central C—C—C angle of 133.5°, associated with a C5—C51 bond length of only 1.21 Å; hence the observed combination of a less extreme C5—C51—C5i angle and the displacement of atom C51 from the plane of the pyrimidine ring.
The molecules of (I) are linked by a second N—H···O hydrogen bond (Table 3) to produce a molecular ribbon consisting of edge-fused running parallel to the [101] direction, in which molecules lying across the series of twofold rotation axes along (0.5n, y, 0.5n-1/4) alternate with centrosymmetric R42(8) rings centred at (0.5n+1/4, y, 0.5n), where n represents an integer in each case (Fig. 2). Two ribbons of this type, related to one another by the C-centring operation, pass through each unit cell, but there are no direction-specific interactions between adjacent ribbons.
Data collection: COLLECT (Hooft, 1998); 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).
Fig. 1. The molecular structure of compound (I), showing the atom-labelling
scheme and the intramolecular N—H···O hydrogen bonds. Displacement
ellipsoids are drawn at the 30% probability level. [Symmetry code: (i)
-x+1, y, -z+1/2.] Fig. 2. Part of the crystal structure of compound (I), showing the formation of a ribbon of edge-fused hydrogen-bonded S(8) and R42(8) rings parallel to the [101] direction. For the sake of clarity, H atoms bonded to C atoms have been omitted. The S21 atoms marked with an asterisk (*), a hash (#), a dollar sign ($), an ampersand (&) or an `at' sign (@) are at the symmetry positions (-x+1, y, -z+1/2), (x+1/2, -y+1/2, z+1/2), (x+1, y, z+1), (-x+3/2, -y+1/2, -z+1) and (-x+2, y, -z+3/2), respectively. |
C13H18N6O2S2 | F(000) = 744 |
Mr = 354.47 | Dx = 1.536 Mg m−3 |
Monoclinic, C2/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -C 2yc | Cell parameters from 1763 reflections |
a = 19.862 (6) Å | θ = 2.9–27.5° |
b = 7.4877 (19) Å | µ = 0.37 mm−1 |
c = 14.236 (5) Å | T = 120 K |
β = 133.61 (2)° | Block, orange |
V = 1533.0 (10) Å3 | 0.31 × 0.24 × 0.16 mm |
Z = 4 |
Bruker–Nonius KappaCCD diffractometer | 1763 independent reflections |
Radiation source: Bruker–Nonius FR591 rotating anode | 1442 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.041 |
Detector resolution: 9.091 pixels mm-1 | θmax = 27.5°, θmin = 2.9° |
ϕ & ω scans | h = −25→25 |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | k = −9→9 |
Tmin = 0.895, Tmax = 0.944 | l = −18→18 |
10706 measured reflections |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.041 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.113 | H-atom parameters constrained |
S = 1.07 | w = 1/[σ2(Fo2) + (0.0598P)2 + 1.8314P] where P = (Fo2 + 2Fc2)/3 |
1763 reflections | (Δ/σ)max = 0.001 |
107 parameters | Δρmax = 0.43 e Å−3 |
0 restraints | Δρmin = −0.47 e Å−3 |
C13H18N6O2S2 | V = 1533.0 (10) Å3 |
Mr = 354.47 | Z = 4 |
Monoclinic, C2/c | Mo Kα radiation |
a = 19.862 (6) Å | µ = 0.37 mm−1 |
b = 7.4877 (19) Å | T = 120 K |
c = 14.236 (5) Å | 0.31 × 0.24 × 0.16 mm |
β = 133.61 (2)° |
Bruker–Nonius KappaCCD diffractometer | 1763 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2003) | 1442 reflections with I > 2σ(I) |
Tmin = 0.895, Tmax = 0.944 | Rint = 0.041 |
10706 measured reflections |
R[F2 > 2σ(F2)] = 0.041 | 0 restraints |
wR(F2) = 0.113 | H-atom parameters constrained |
S = 1.07 | Δρmax = 0.43 e Å−3 |
1763 reflections | Δρmin = −0.47 e Å−3 |
107 parameters |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
N1 | 0.40451 (10) | 0.2749 (2) | 0.37455 (14) | 0.0221 (3) | |
C2 | 0.47983 (12) | 0.2819 (2) | 0.49776 (17) | 0.0210 (4) | |
N3 | 0.56632 (10) | 0.2293 (2) | 0.55153 (14) | 0.0218 (3) | |
C4 | 0.57747 (13) | 0.1544 (2) | 0.47152 (18) | 0.0213 (4) | |
C5 | 0.49617 (13) | 0.1386 (2) | 0.33850 (18) | 0.0213 (4) | |
C6 | 0.41280 (13) | 0.2054 (2) | 0.29338 (17) | 0.0218 (4) | |
S21 | 0.47580 (3) | 0.36659 (6) | 0.60877 (4) | 0.02434 (17) | |
C21 | 0.35233 (14) | 0.3784 (3) | 0.5089 (2) | 0.0300 (4) | |
H21A | 0.3243 | 0.4568 | 0.4346 | 0.045* | |
H21B | 0.3400 | 0.4262 | 0.5599 | 0.045* | |
H21C | 0.3254 | 0.2586 | 0.4777 | 0.045* | |
C31 | 0.64794 (13) | 0.2467 (3) | 0.69125 (18) | 0.0275 (4) | |
H31A | 0.6598 | 0.3733 | 0.7152 | 0.041* | |
H31B | 0.7022 | 0.1939 | 0.7124 | 0.041* | |
H31C | 0.6363 | 0.1844 | 0.7394 | 0.041* | |
O41 | 0.65766 (9) | 0.10876 (18) | 0.52349 (13) | 0.0255 (3) | |
C51 | 0.5000 | 0.0381 (4) | 0.2500 | 0.0227 (5) | |
H51A | 0.4448 | −0.0407 | 0.1945 | 0.027* | 0.50 |
H51B | 0.5552 | −0.0407 | 0.3055 | 0.027* | 0.50 |
N61 | 0.33348 (11) | 0.2033 (2) | 0.16687 (15) | 0.0274 (4) | |
H61A | 0.3307 | 0.1749 | 0.1042 | 0.033* | |
H61B | 0.2844 | 0.2608 | 0.1408 | 0.033* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0212 (8) | 0.0270 (8) | 0.0231 (8) | −0.0010 (6) | 0.0171 (7) | 0.0002 (6) |
C2 | 0.0212 (9) | 0.0221 (9) | 0.0242 (9) | 0.0003 (7) | 0.0174 (8) | 0.0019 (7) |
N3 | 0.0201 (8) | 0.0269 (8) | 0.0210 (7) | 0.0007 (6) | 0.0152 (7) | 0.0017 (6) |
C4 | 0.0231 (9) | 0.0211 (9) | 0.0260 (9) | 0.0003 (7) | 0.0193 (8) | 0.0029 (7) |
C5 | 0.0236 (9) | 0.0215 (9) | 0.0249 (9) | −0.0014 (7) | 0.0191 (8) | −0.0014 (7) |
C6 | 0.0214 (9) | 0.0236 (9) | 0.0238 (9) | −0.0031 (7) | 0.0169 (8) | −0.0007 (7) |
S21 | 0.0246 (3) | 0.0302 (3) | 0.0237 (3) | 0.00031 (19) | 0.0187 (2) | −0.00003 (18) |
C21 | 0.0258 (9) | 0.0410 (12) | 0.0284 (10) | 0.0040 (9) | 0.0207 (9) | 0.0012 (9) |
C31 | 0.0218 (9) | 0.0393 (11) | 0.0226 (9) | 0.0013 (8) | 0.0157 (8) | 0.0027 (8) |
O41 | 0.0209 (7) | 0.0334 (8) | 0.0252 (7) | 0.0021 (6) | 0.0170 (6) | 0.0029 (6) |
C51 | 0.0239 (12) | 0.0239 (13) | 0.0262 (13) | 0.000 | 0.0195 (11) | 0.000 |
N61 | 0.0207 (8) | 0.0409 (10) | 0.0232 (8) | 0.0014 (7) | 0.0162 (7) | −0.0023 (7) |
N1—C2 | 1.303 (2) | C21—H21A | 0.9800 |
N1—C6 | 1.377 (2) | C21—H21B | 0.9800 |
C2—N3 | 1.370 (2) | C21—H21C | 0.9800 |
C2—S21 | 1.7553 (19) | C31—H31A | 0.9800 |
N3—C4 | 1.417 (2) | C31—H31B | 0.9800 |
N3—C31 | 1.467 (2) | C31—H31C | 0.9800 |
C4—O41 | 1.255 (2) | C51—C5i | 1.514 (2) |
C4—C5 | 1.410 (3) | C51—H51A | 0.9900 |
C5—C6 | 1.392 (3) | C51—H51B | 0.9900 |
C5—C51 | 1.514 (2) | N61—H61A | 0.8798 |
C6—N61 | 1.346 (2) | N61—H61B | 0.8800 |
S21—C21 | 1.798 (2) | ||
C2—N1—C6 | 117.02 (16) | H21A—C21—H21B | 109.5 |
N1—C2—N3 | 124.99 (16) | S21—C21—H21C | 109.5 |
N1—C2—S21 | 120.24 (14) | H21A—C21—H21C | 109.5 |
N3—C2—S21 | 114.76 (13) | H21B—C21—H21C | 109.5 |
C2—N3—C4 | 119.68 (15) | N3—C31—H31A | 109.5 |
C2—N3—C31 | 121.27 (15) | N3—C31—H31B | 109.5 |
C4—N3—C31 | 119.04 (15) | H31A—C31—H31B | 109.5 |
O41—C4—C5 | 125.50 (17) | N3—C31—H31C | 109.5 |
O41—C4—N3 | 118.18 (16) | H31A—C31—H31C | 109.5 |
C5—C4—N3 | 116.32 (16) | H31B—C31—H31C | 109.5 |
C6—C5—C4 | 119.04 (17) | C5—C51—C5i | 120.3 (2) |
C6—C5—C51 | 121.42 (15) | C5—C51—H51A | 107.2 |
C4—C5—C51 | 119.40 (15) | C5i—C51—H51A | 107.2 |
N61—C6—N1 | 114.86 (17) | C5—C51—H51B | 107.2 |
N61—C6—C5 | 122.35 (17) | C5i—C51—H51B | 107.2 |
N1—C6—C5 | 122.77 (17) | H51A—C51—H51B | 106.9 |
C2—S21—C21 | 100.96 (10) | C6—N61—H61A | 123.8 |
S21—C21—H21A | 109.5 | C6—N61—H61B | 119.5 |
S21—C21—H21B | 109.5 | H61A—N61—H61B | 114.4 |
C6—N1—C2—N3 | 1.6 (3) | O41—C4—C5—C51 | 8.4 (3) |
C6—N1—C2—S21 | −179.46 (13) | N3—C4—C5—C51 | −171.97 (16) |
N1—C2—N3—C4 | −2.6 (3) | C2—N1—C6—N61 | −179.08 (17) |
S21—C2—N3—C4 | 178.35 (13) | C2—N1—C6—C5 | 2.3 (3) |
N1—C2—N3—C31 | 178.27 (18) | C4—C5—C6—N61 | 176.56 (18) |
S21—C2—N3—C31 | −0.8 (2) | C51—C5—C6—N61 | −7.9 (3) |
C2—N3—C4—O41 | 179.51 (16) | C4—C5—C6—N1 | −4.9 (3) |
C31—N3—C4—O41 | −1.4 (3) | C51—C5—C6—N1 | 170.59 (18) |
C2—N3—C4—C5 | −0.2 (2) | N1—C2—S21—C21 | 11.36 (18) |
C31—N3—C4—C5 | 178.98 (16) | N3—C2—S21—C21 | −169.56 (14) |
O41—C4—C5—C6 | −175.99 (17) | C4—C5—C51—C5i | −102.25 (17) |
N3—C4—C5—C6 | 3.6 (2) | C6—C5—C51—C5i | 82.24 (17) |
Symmetry code: (i) −x+1, y, −z+1/2. |
D—H···A | D—H | H···A | D···A | D—H···A |
N61—H61A···O41i | 0.88 | 2.05 | 2.921 (3) | 173 |
N61—H61B···O41ii | 0.88 | 2.07 | 2.917 (3) | 162 |
Symmetry codes: (i) −x+1, y, −z+1/2; (ii) x−1/2, −y+1/2, z−1/2. |
Experimental details
Crystal data | |
Chemical formula | C13H18N6O2S2 |
Mr | 354.47 |
Crystal system, space group | Monoclinic, C2/c |
Temperature (K) | 120 |
a, b, c (Å) | 19.862 (6), 7.4877 (19), 14.236 (5) |
β (°) | 133.61 (2) |
V (Å3) | 1533.0 (10) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.37 |
Crystal size (mm) | 0.31 × 0.24 × 0.16 |
Data collection | |
Diffractometer | Bruker–Nonius KappaCCD diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 2003) |
Tmin, Tmax | 0.895, 0.944 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 10706, 1763, 1442 |
Rint | 0.041 |
(sin θ/λ)max (Å−1) | 0.650 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.041, 0.113, 1.07 |
No. of reflections | 1763 |
No. of parameters | 107 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.43, −0.47 |
Computer programs: COLLECT (Hooft, 1998), DIRAX/LSQ (Duisenberg et al., 2000), EVALCCD (Duisenberg et al., 2003), SIR2004 (Burla et al., 2005), SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).
C5—C51 | 1.514 (2) | ||
C5—C51—C5i | 120.3 (2) | ||
N1—C2—S21—C21 | 11.36 (18) | C4—C5—C51—C5i | −102.25 (17) |
N3—C2—S21—C21 | −169.56 (14) | C6—C5—C51—C5i | 82.24 (17) |
Symmetry code: (i) −x+1, y, −z+1/2. |
D—H···A | D—H | H···A | D···A | D—H···A |
N61—H61A···O41i | 0.88 | 2.05 | 2.921 (3) | 173 |
N61—H61B···O41ii | 0.88 | 2.07 | 2.917 (3) | 162 |
Symmetry codes: (i) −x+1, y, −z+1/2; (ii) x−1/2, −y+1/2, z−1/2. |