Three hexa­hydro­pyrido­pyrimidine-spiro-cyclo­hexane­triones: supra­molecular structures generated by O—H⋯O, N—H⋯O, C—H⋯O and C—H⋯π hydrogen bonds, and π–π stacking interactions

Low, J.N.; Ferguson, G.; Cobo, J.; Nogueras, M.; Cruz, S.; Quiroga, J.; Glidewell, C.

doi:10.1107/S0108270104009539

organic compounds

STRUCTURAL
CHEMISTRY

ISSN: 2053-2296

Volume 60| Part 6| June 2004| Pages o438-o443

doi:10.1107/S0108270104009539

Three hexahydropyridopyrimidine-spiro-cyclohexanetriones: supramolecular structures generated by O—H⋯O, N—H⋯O, C—H⋯O and C—H⋯π hydrogen bonds, and π–π stacking interactions

John N. Low,^a ‡ George Ferguson,^b Justo Cobo,^c Manuel Nogueras,^c Silvia Cruz,^d Jairo Quiroga ^e and Christopher Glidewell ^f ^*

^aDepartment of Chemistry, University of Aberdeen, Meston Walk, Old Aberdeen AB24 3UE, Scotland, ^bDepartment of Chemistry, University of Guelph, Ontario, Canada N1G 2W1, ^cDepartamento de Química Inorgánica y Orgánica, Universidad de Jaén, 23071 Jaén, Spain, ^dDepartamento de Química, Universidad de Nariño, Cuidad Universitaria, Torobajo, AA 1175, Pasto, Colombia, ^eGrupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad de Valle, AA 25360, Cali, Colombia, and ^fSchool of Chemistry, University of St Andrews, Fife KY16 9ST, Scotland
^*Correspondence e-mail: cg@st-andrews.ac.uk

(Received 14 April 2004; accepted 20 April 2004; online 22 May 2004)

4′,4′-Dimethyl-2-methylsulfanyl-3,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidine-6-spiro-1′-cyclohexane-2′,4,6′-trione, C₁₅H₁₉N₃O₃S, (I), has a markedly polarized molecular–electronic structure, and the molecules are linked into a three-dimensional framework by a combination of N—H⋯O, C—H⋯O and C—H⋯π hydrogen bonds. 8-Hydroxymethyl-4′,4′-dimethyl-2-methylsulfanyl-3,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidine-6-spiro-1′-cyclohexane-2′,4,6′-trione, C₁₆H₂₁N₃O₄S, (II), where the hydroxymethyl substituent is disordered over two sets of sites, has a much less polarized structure than (I); the molecules are linked by a combination of O—H⋯O and N—H⋯O hydrogen bonds into chains containing alternating [R_2^2] (8) and [R_2^2] (16) rings, and these chains are linked into sheets by a combination of a π–π stacking interaction and a C—H⋯O hydrogen bond. 8-Ethoxymethyl-2-methoxy-4′,4′-dimethyl-3,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidine-6-spiro-1′-cyclohexane-2′,4,6′-trione, C₁₈H₂₅N₃O₅, (III), has an unpolarized electronic structure, and a combination of N—H⋯O, C—H⋯O and C—H⋯π hydrogen bonds links the molecules into sheets.

Comment

reactions between 4-aminopyrimidin-4(3H)-ones, dimedone (5,5-dimethyl-1,3-cyclohexanedione) and simple aliphatic aldehydes, in the expectation of forming pyrimidinoquinolines. In the event, reactions of this type, using an excess of formaldehyde in the presence of triethylamine, have led to the formation of spiro compounds rather than the expected pyrimidinoquinolines, and we report here the molecular and supramolecular structures of three such compounds, (I

)–(III

). All of the molecules are chiral, but the compounds studied all crystallize in the centrosymmetric space group $[P \overline 1]$ and hence are racemic. The structure of (II

) is complicated by the disorder of the –CH₂OH substituent at atom N8, which was modelled using sets of sites, each with an occupancy of 0.5, corresponding to two distinct orientations for this group.

The bond lengths in (I) (Fig. 1 and Table 1) show some discrepancies when compared with typical values for bonds of similar types (Allen et al., 1987 ). For example, the N3—C4 and C4—O4 bonds are both long for their types, the C4—C4A and C4A—C8A bonds are too similar in length to be characterized as single and double bonds, respectively, and the C8A—N8 bond, involving a three-coordinate N atom, is much shorter than the C8A—N1 bond, which involves a two-coordinate N atom. These observations, taken together, effectively preclude the polarized form (Ia) as an effective contributor to the overall molecular–electronic structure, instead pointing to the importance of the polarized vinylogous amide form (Ib).

Compounds (II) and (III) (Figs. 2 and 3) both show a much smaller degree of electronic polarization. For example, the difference between the C8A—N1 and C8A—N8 bond lengths (Tables 3 and 5) is much smaller in (II) and (III) than in (I). Hence, for these compounds, the classically localized forms are the most appropriate representations. We also note here the much greater difference between the C2—O2 and O2—C21 distances in (III) (∼0.11 Å) than between the corresponding C2—S2 and S2—C21 distances in (I) and (II) (∼0.04 and ∼0.02 Å, respectively). In each compound, the exocyclic bond angles at atom C2 are very different from 120°.

In each of (I)–(III), the ring containing atoms N1 and N3 is effectively planar, but for the ring containing atom N8, the ring-puckering parameters (Cremer & Pople, 1975 ) corresponding to the atom sequence N8—C7—C6—C5—C4A—C8A [θ = 129.2 (2)° and φ = 304.5 (3)° in (I), θ = 51.3 (3)° and φ = 98.5 (3)° in (II), and θ = 126.5 (3)° and φ = 283.2 (4)° in (III)] indicate that, in each compound, the conformation of this ring is best described as an envelope form, itself dominated by a combination of boat and chair forms (Evans & Boeyens, 1989 ). The carbocyclic rings adopt almost perfect chair conformations, with local pseudo-mirror symmetry defined by the plane through atoms C6, C63, C631 and C632. The conformations of the pendent CH₃X substituents [X = S in (I) and (II), and O in (III)] are similar in (I)–(III), while the –CH₂OEt unit in (III) exhibits some unusual torsion angles (Table 5).

The molecules of (I) are linked into a three-dimensional framework by a combination of N—H⋯O, C—H⋯O and C—H⋯π hydrogen bonds (Table 2). Two independent N—H⋯O hydrogen bonds generate a one-dimensional substructure in the form of a chain of rings; these chains are linked into sheets by the C—H⋯O hydrogen bonds, and the sheets are linked by C—H⋯π hydrogen bonds. Atom N3 in the molecule at (x, y, z) acts as a donor to atom O4 in the molecule at (1 − x, 1 − y, 1 − z), so forming a centrosymmetric [R_2^2] (8) ring, centred at ( $[1 \over 2]$ , $[1 \over 2]$ , $[1 \over 2]$ ) (Fig. 4). Similarly, atom N8 at (x, y, z) acts as a donor to atom O65 in the molecule at (−x, 1 − y, −z), forming a centrosymmetric [R_2^2] (12) motif, this time centred at (0, $[1 \over 2]$ , 0). The propagation by inversion of these two motifs generates a chain running parallel to the [101] direction. Atom C5 in the molecule at (x, y, z) acts as a hydrogen-bond donor to atom O61 in the molecule at (−x, 2 − y, −z), so forming a third centrosymmetric ring motif, of [R_2^2] (10) type, centred at (0, 1, 0). The combination of this motif with the [101] chains generates a (10 $[\overline 1]$ ) sheet (Fig. 4) containing four distinct types of ring, all centrosymmetric; in addition to the [R_2^2] (8), [R_2^2] (10) and [R_2^2] (12) types already described, the sheet also contains R₆⁶(34) rings. Finally, atom C64 in the molecule at (x, y, z), which lies in the sheet passing through ( $[1 \over 2]$ , $[1 \over 2]$ , $[1 \over 2]$ ), acts as a hydrogen-bond donor, via H64A, to the N1/C2/N3/C4/C4A/C8A ring in the molecule at (1 − x, 1 − y, −z), which lies in the sheet passing through ( $[1 \over 2]$ , $[1 \over 2]$ , − $[1 \over 2]$ ). The formation of this further centrosymmetric motif (Fig. 5) thus serves to link all of the centrosymmetric sheets into a single framework.

The molecules of (II) are linked by a combination of N—H⋯O and O—H⋯O hydrogen bonds (Table 4) into chains, and these chains are linked into sheets by a combination of a C—H⋯O hydrogen bond and a π–π stacking interaction. The description of the supramolecular aggregation is complicated by the disorder of the pendent –CH₂OH unit. Atom N3 in the molecule at (x, y, z) acts as a hydrogen-bond donor to carbonyl atom O4 in the molecule at (2 − x, 1 − y, 1 − z), so forming a fully ordered [R_2^2] (8) motif centred at (1, $[1 \over 2]$ , $[1 \over 2]$ ). In addition, the partially occupied O8A site at (x, y, z) acts as a donor to carboxyl atom O61 in the molecule at (1 − x, 1 − y, −z). There is also a much longer, and hence presumably weaker, O—H⋯O interaction involving the alternative atom site, O8B, as a donor and the same O61 atom as an acceptor. Hence, regardless of which site, O8A or O8B, is occupied, there will be two O—H⋯O linkages between the pair of molecules in question, forming an [R_2^2] (16) ring. If the O8A sites were occupied in both molecules, the ring would be centrosymmetric. At the local level, such pairs of molecules can, in fact, be linked by zero, one or two strong O—H⋯O hydrogen bonds, with a mean of one such bond. In any event, the combination of the N—H⋯O and O—H⋯O hydrogen bonds generates a chain of rings running parallel to the [101] direction (Fig. 6).

Two weaker interactions combine to link the [101] chains into sheets. The N1/C2/N3/C4/C4A/C8A rings in the molecules at (x, y, z) and (1 − x, 1 − y, 1 − z) are parallel, with an interplanar spacing of 3.583 (2) Å; the ring-centroid separation is 3.878 (2) Å, corresponding to a centroid offset of 1.484 (2) Å (Fig. 7). The molecules involved lie in adjacent [101] chains, separated by a unit translation along [100]. This interaction is reinforced by a single C—H⋯O hydrogen bond; atom C62 in the molecule at (x, y, z) acts as a donor, via H62B, to the partially occupied O8A site in the molecule at (−x, 1 − y, −z) (Fig. 8).

In (III), the molecules are linked into sheets by a combination of N—H⋯O, C—H⋯O and C—H⋯π hydrogen bonds (Table 6). Pairs of N—H⋯O and of C—H⋯O hydrogen bonds generate a chain containing two types of centrosymmetric ring, and these chains are linked by C—H⋯π hydrogen bonds. Amine atom N3 in the molecule at (x, y, z) acts as a hydrogen-bond donor to amide atom O4 in the molecule at (1 − x, 1 − y, 1 − z), thereby generating a centrosymmetric [R_2^2] (8) motif centred at ( $[1 \over 2]$ , $[1 \over 2]$ , $[1 \over 2]$ ). In addition, ring atom C7 at (x, y, z) acts as a donor, via H7B, to the exocyclic atom O81 in the molecule at (3 − x, −y, 1 − z), so forming an [R_2^2] (10) ring centred at ( $[3 \over 2]$ , 0, $[1 \over 2]$ ). Propagation by inversion of these two hydrogen bonds then generates a chain running parallel to the [2 $[\overline 1]$ 0] direction, in which [R_2^2] (8) and [R_2^2] (10) rings alternate (Fig. 9). Finally, atom C7 in the molecule at (x, y, z), which is part of the [2 $[\overline 1]$ 0] chain passing through ( $[1 \over 2]$ , $[1 \over 2]$ , $[1 \over 2]$ ), acts as a hydrogen-bond donor, via H7A, to the N1/C2/N3/C4/C4A/C8A ring in the molecule at (2 − x, −y, 1 − z), which itself lies in the [2 $[\overline 1]$ 0] chain passing through (− $[1 \over 2]$ , $[1 \over 2]$ , $[1 \over 2]$ ). The resulting centrosymmetric motif (Fig. 10) thus serves to link [2 $[\overline 1]$ 0] chains into a (001) sheet. Although the structures of both (I) and (III) contain C—H⋯π hydrogen bonds, they differ in that the donor atoms lie in different rings in the two compounds.

The formation of (I) from the precursor aminopyrimidine, dimedone and two molecules of formaldehyde is straightforward, proceeding via the intermediate (IV); we have recently reported the structure of the N³-methyl analogue of (IV) (Low et al., 2004 ). Further reaction at the secondary amine atom N8 of the primary product of type (A) with another molecule of formaldehyde in the presence of ethanol can lead, via a hydroxymethyl derivative, (B) [cf. compound (II)], to an ethoxymethyl product, (C) [cf. compound (III)].

Figure 1
The molecule of (I

), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.

Figure 2
The molecule of (II

), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. For clarity, only one orientation of the disordered –CH₂OH substituent is shown.

Figure 3
The molecule of (III

), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.

Figure 4
Part of the crystal structure of (I

), showing the formation of a (10 $[\overline 1]$ ) sheet containing four types of centrosymmetric ring. For clarity, H atoms bonded to atoms not involved in the motifs shown have been omitted. Atoms marked with an asterisk (*), an ampersand (&), a plus sign (+), an `at' sign (@), a dollar sign ($) or a hash (#) are at the symmetry positions (1 − x, 1 − y, 1 − z), (1 + x, y, 1 + z), (1 − x, 2 − y, 1 − z), (x, 1 + y, z), (−x, 2 − y, −z) and (−x, 1 − y, −z), respectively.

Figure 5
Part of the crystal structure of (I

), showing the centrosymmetric linking of the molecules by pairs of C—H⋯π hydrogen bonds. For clarity, H atoms bonded to atoms not involved in the motif shown have been omitted. Atoms marked with an asterisk (*) are at the symmetry position (1 − x, 1 − y, −z).

Figure 6
A stereoview of part of the crystal structure of (II

), showing the formation of a chain of rings along [101]. For clarity, H atoms bonded to C atoms have been omitted and only one orientation of the disordered –CH₂OH group is shown.

Figure 7
Part of the crystal structure of (II

), showing the π–π stacking interaction that links the [101] chains into sheets. For clarity, H atoms bonded to C atoms have been omitted, the unit-cell box has been omitted and only one orientation of the disordered –CH₂OH group is shown.

Figure 8
A stereoview of part of the crystal structure of (II

), showing the action of the C—H⋯O hydrogen bond in linking adjacent [101] chains. For clarity, H atoms bonded to C atoms but not involved in the motif shown have been omitted, and only one orientation of the disordered –CH₂OH group is shown.

Figure 9
Part of the crystal structure of (III

), showing the formation of a [2 $[\overline 1]$ 0] chain of centrosymmetric [R_2^2]

(8) and

(10) rings. For clarity, H atoms bonded to atoms not involved in the motif shown have been omitted. Atoms marked with an asterisk (*), a hash (#) or a dollar sign ($) are at the symmetry positions (1 − x, 1 − y, 1 − z), (3 − x, −y, 1 − z) and (−2 + x, 1 + y, z), respectively.

Figure 10
Part of the crystal structure of (III

), showing the centrosymmetric linking of the molecules by pairs of C—H⋯π hydrogen bonds. For clarity, H atoms bonded to atoms not involved in the motif shown have been omitted. The atom marked with an asterisk (*) is at the symmetry position (2 − x, −y, 1 − z).

Experimental

For the preparation of (I), dimedone (2 mmol), a large excess of an aqueous solution (37% w/w) of formaldehyde (30 mmol formaldehyde) and triethylamine (0.5 mmol) were added to a solution of 6-amino-2-methylsulfanyl-3,4-dihydropyrimidin-4-one (2 mmol) in ethanol, and this mixture was heated under reflux for 90 min. After cooling the mixture, the resulting white product, (I), was filtered off and washed with ethanol (m.p. 563–567 K). Analysis found: C 55.7, H 5.8, N 12.8, S 10.0%; C₁₅H₁₉N₃O₃S requires: C 13.1, H 6.0, N 13.1, S 10.0%. Compound (II) was an occasional and erratic by-product of this reaction. For the preparation of (III), dimedone (2 mmol) and a large excess of an aqueous solution (37% w/w) of formaldehyde (30 mmol) were added to a solution of 6-amino-2-methoxy-3,4-dihydropyrimidin-4-one (2 mmol) in ethanol, and this mixture was heated under reflux for 90 min. After cooling the mixture, the resulting white product, (III), was filtered off and washed with ethanol (m.p. 533–536 K). For (I) and (II), crystals suitable for single-crystal X-ray diffraction were grown from solutions in wet dimethyl sulfoxide; crystals of (III) suitable for single-crystal X-ray diffraction were grown from a solution in ethanol.

Compound (I)

Crystal data

C₁₅H₁₉N₃O₃S
M_r = 321.39
Triclinic, $[P\overline 1]$
a = 7.8990 (3) Å
b = 10.0386 (3) Å
c = 10.0500 (3) Å
α = 74.938 (2)°
β = 84.271 (2)°
γ = 81.842 (2)°
V = 760.10 (4) Å³
Z = 2
D_x = 1.404 Mg m⁻³
Mo Kα radiation
Cell parameters from 3462 reflections
θ = 3.2–27.5°
μ = 0.23 mm⁻¹
T = 120 (2) K
Block, colourless
0.42 × 0.38 × 0.20 mm

Data collection

Nonius KappaCCD diffractometer
φ scans, and ω scans with κ offsets
Absorption correction: multi-scan (SORTAV; Blessing, 1995 , 1997 ) T_min = 0.921, T_max = 0.956
15 364 measured reflections
3462 independent reflections
2923 reflections with I > 2σ(I)
R_int = 0.057
θ_max = 27.5°
h = −10 → 10
k = −12 → 12
l = −12 → 13

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.046
wR(F²) = 0.125
S = 1.04
3462 reflections
202 parameters
H-atom parameters constrained
w = 1/[σ²(F_o² + (0.0595P)² + 0.5301P] where P = (F_o² + 2F_c²)/3
(Δ/σ)_max < 0.001
Δρ_max = 1.00 e Å⁻³
Δρ_min = −0.42 e Å⁻³

Table 1
Selected geometric parameters (Å, °) for (I)

N1—C2	1.300 (2)
C2—N3	1.356 (2)
N3—C4	1.395 (2)
C4—C4A	1.409 (2)
C4A—C8A	1.391 (2)
C8A—N1	1.379 (2)
C4—O4	1.253 (2)
C8A—N8	1.342 (2)
C7—N8	1.455 (2)
C2—S2	1.7547 (18)
S2—C21	1.7983 (19)
C61—O61	1.216 (2)
C65—O65	1.219 (2)

N1—C2—N3	125.04 (16)
N1—C2—S2	121.25 (14)
N3—C2—S2	113.71 (13)
C2—S2—C21	100.96 (9)

C4A—C5—C6—C7	51.41 (18)
C5—C6—C7—N8	−50.4 (2)
C6—C7—N8—C8A	26.8 (3)
C7—N8—C8A—C4A	−2.5 (3)
N8—C8A—C4A—C5	4.8 (3)
C8A—C4A—C5—C6	−30.3 (2)
C6—C61—C62—C63	58.5 (2)
C61—C62—C63—C64	−56.58 (18)
C62—C63—C64—C65	54.3 (2)
C63—C64—C65—C6	−53.2 (2)
C64—C65—C6—C61	49.58 (19)
C65—C6—C61—C62	−52.5 (2)

Table 2
Hydrogen-bonding geometry (Å, °) for (I)

Cg1 is the centroid of the N1/C2/N3/C4/C4A/C8A ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3⋯O4ⁱ	0.88	1.84	2.715 (2)	176
N8—H8⋯O65ⁱⁱ	0.88	2.10	2.965 (2)	166
C5—H5B⋯O61ⁱⁱⁱ	0.99	2.46	3.389 (2)	155
C64—H64A⋯Cg1^iv	0.99	2.87	3.854 (2)	173
Symmetry codes: (i) 1-x,1-y,1-z; (ii) -x,1-y,-z; (iii) -x,2-y,-z; (iv) 1-x,-y,-z.

Compound (II)

Crystal data

C₁₆H₂₁N₃O₄S
M_r = 351.42
Triclinic, $[P\overline 1]$
a = 6.6682 (2) Å
b = 11.0319 (3) Å
c = 12.3449 (4) Å
α = 109.2678 (18)°
β = 99.8329 (18)°
γ = 101.227 (2)°
V = 813.32 (5) Å³
Z = 2
D_x = 1.435 Mg m⁻³
Mo Kα radiation
Cell parameters from 3737 reflections
θ = 3.2–27.5°
μ = 0.23 mm⁻¹
T = 120 (2) K
Plate, colourless
0.15 × 0.10 × 0.03 mm

Data collection

Nonius KappaCCD diffractometer
φ scans, and ω scans with κ offsets
Absorption correction: multi-scan (SORTAV; Blessing, 1995, 1997) T_min = 0.976, T_max = 0.994
18 379 measured reflections
3737 independent reflections
2502 reflections with I > 2σ(I)
R_int = 0.047
θ_max = 27.5°
h = −8 → 8
k = −14 → 14
l = −15 → 16

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.051
wR(F²) = 0.140
S = 1.03
3737 reflections
238 parameters
H-atom parameters constrained
w = 1/[σ²(F_o²) + (0.066P)² + 0.2491P] where P = (F_o² + 2F_c²)/3
(Δ/σ)_max < 0.001
Δρ_max = 0.28 e Å⁻³
Δρ_min = −0.41 e Å⁻³

Table 3
Selected geometric parameters (Å, °) for (II)

N1—C2	1.294 (3)
C2—N3	1.334 (3)
N3—C4	1.395 (3)
C4—C4A	1.414 (3)
C4A—C8A	1.374 (3)
C8A—N1	1.379 (3)
C4—O4	1.239 (3)
C8A—N8	1.362 (3)
C7—N8	1.456 (2)
C2—S2	1.756 (2)
S2—C21	1.779 (3)
C61—O61	1.212 (2)
C65—O65	1.206 (2)

N1—C2—N3	124.60 (19)
N1—C2—S2	121.14 (19)
N3—C2—S2	114.25 (17)
C2—S2—C21	99.74 (12)

C4A—C5—C6—C7	−46.1 (2)
C5—C6—C7—N8	59.0 (2)
C6—C7—N8—C8A	−42.4 (3)
C7—N8—C8A—C4A	12.1 (3)
N8—C8A—C4A—C5	1.0 (3)
C8A—C4A—C5—C6	18.1 (3)
C6—C7—N8—C81A	139.6 (4)
C7—N8—C81A—O8A	−61.9 (14)
C6—C61—C62—C63	−55.9 (2)
C61—C62—C63—C64	56.3 (2)
C62—C63—C64—C65	−55.6 (3)
C63—C64—C65—C6	52.5 (2)
C64—C65—C6—C61	−45.7 (2)
C65—C6—C61—C62	48.1 (2)
C6—C7—N8—C81B	158.5 (4)
C7—N8—C81B—O8B	−113.3 (9)

Table 4
Hydrogen-bonding geometry (Å, °) for (II)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3⋯O4^v	0.88	1.83	2.709 (3)	176
O8A—H8A⋯O61^vi	0.84	2.00	2.767 (3)	152
O8B—H8B⋯O61^vi	0.84	2.35	3.036 (4)	139
C62—H62B⋯O8Aⁱⁱ	0.99	2.33	3.314 (4)	173
Symmetry codes: (ii) -x,1-y,-z; (v) 2-x,1-y,1-z; (vi) 1-x,1-y,-z.

Compound (III)

Crystal data

C₁₈H₂₅N₃O₅
M_r = 363.41
Triclinic, $[P\overline 1]$
a = 8.9219 (5) Å
b = 9.9806 (5) Å
c = 11.3542 (7) Å
α = 75.662 (3)°
β = 85.580 (3)°
γ = 66.526 (3)°
V = 898.22 (9) Å³
Z = 2
D_x = 1.344 Mg m⁻³
Mo Kα radiation
Cell parameters from 4082 reflections
θ = 2.9–27.6°
μ = 0.10 mm⁻¹
T = 120 (2) K
Prism, colourless
0.15 × 0.10 × 0.10 mm

Data collection

Nonius KappaCCD diffractometer
φ scans, and ω scans with κ offsets
Absorption correction: multi-scan (SORTAV; Blessing, 1995, 1997) T_min = 0.967, T_max = 0.990
17 797 measured reflections
4082 independent reflections
2026 reflections with I > 2σ(I)
R_int = 0.088
θ_max = 27.6°
h = −11 → 11
k = −12 → 12
l = −14 → 14

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.056
wR(F²) = 0.164
S = 0.95
4082 reflections
239 parameters
H-atom parameters constrained
w = 1/[σ²(F_o²) + (0.0803P)²] where P = (F_o² + 2F_c²)/3
(Δ/σ)_max < 0.001
Δρ_max = 0.30 e Å⁻³
Δρ_min = −0.43 e Å⁻³

Table 5
Selected geometric parameters (Å, °) for (III)

N1—C2	1.292 (3)
C2—N3	1.343 (3)
N3—C4	1.388 (3)
C4—C4A	1.412 (3)
C4A—C8A	1.378 (3)
C8A—N1	1.375 (3)
C4—O4	1.250 (3)
C8A—N8	1.370 (3)
C7—N8	1.451 (3)
C2—O2	1.334 (3)
O2—C21	1.447 (3)
C61—O61	1.213 (3)
C65—O65	1.210 (3)

N1—C2—N3	125.1 (2)
N1—C2—O2	121.8 (2)
N3—C2—O2	113.1 (2)
C2—O2—C21	115.51 (18)

C4A—C5—C6—C7	47.6 (3)
C5—C6—C7—N8	−58.7 (2)
C6—C7—N8—C8A	39.4 (3)
C7—N8—C8A—C4A	−7.4 (3)
N8—C8A—C4A—C5	−3.4 (4)
C8A—C4A—C5—C6	−18.9 (3)
C6—C7—N8—C81	−142.4 (2)
C7—N8—C81—O81	74.4 (3)
C6—C61—C62—C63	55.5 (3)
C61—C62—C63—C64	−56.8 (3)
C62—C63—C64—C65	55.1 (3)
C63—C64—C65—C6	−51.0 (3)
C64—C65—C6—C61	44.1 (3)
C65—C6—C61—C62	−46.8 (3)
N8—C81—O81—C82	71.3 (3)
C81—O81—C82—C83	82.4 (3)

Table 6
Hydrogen-bonding geometry (Å, °) for (III)

Cg1 is the centroid of the N1/C2/N3/C4/C4A/C8A ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3⋯O4ⁱ	0.88	1.89	2.769 (2)	173
C7—H7B⋯O81^vii	0.99	2.49	3.414 (3)	155
C7—H7A⋯Cg1^viii	0.99	2.62	3.535 (3)	155
Symmetry codes: (i) 1-x,1-y,1-z; (vii) 3-x,-y,1-z; (viii) 2-x,-y,1-z.

Crystals of (I)–(III) are triclinic; space group $[P\overline 1]$ was selected for each and confirmed by the subsequent structure analyses. In (II), the hydroxymethyl substituent is disordered; it was modelled using two sets of atom sites (C81A/O8A for one orientation and C81B/O8B for the other), all atoms having an occupancy of 0.50. All H atoms were located from difference maps and then treated as riding atoms, with C—H distances of 0.98 (CH₃) or 0.99 Å (CH₂), N—H distances of 0.88 Å and O—H distances of 0.84 Å, and with U_iso(H) values of 1.2U_eq(X) (X = C, N and O) [1.5U_eq(C) for the methyl groups].

For all compounds, data collection: KappaCCD Server Software (Nonius, 1997); cell refinement: DENZO–SMN (Otwinowski & Minor, 1997 ); data reduction: DENZO–SMN; program(s) used to solve structure: OSCAIL (McArdle, 2003 ) [for (I) and (II)] and SHELXS97 (Sheldrick, 1997 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003 ); software used to prepare material for publication: SHELXL97 and PRPKAPPA (Ferguson, 1999 ).

Supporting information

Crystal structure: contains datablocks global, I, II, III. DOI: 10.1107/S0108270104009539/sk1722sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S0108270104009539/sk1722Isup2.hkl

Structure factors: contains datablock II. DOI: 10.1107/S0108270104009539/sk1722IIsup3.hkl

Structure factors: contains datablock III. DOI: 10.1107/S0108270104009539/sk1722IIIsup4.hkl

Comment top

Dihydropyridine systems are of current interest because of their exceptional properties as calcium antagonists (Bossert & Vater, 1989) and as powerful arteriolar vasodilators (Kazda & Towart, 1981). As part of a search for new fused heterocyclic systems containing dihydropyridine units, we have been exploring the use of three-component cyclocondensation reactions between 4-aminopyrimidin-4(3H)-ones, dimedone (5,5-dimethyl-1,3-cyclohexanedione) and simple aliphatic aldehydes, in the expectation of forming pyrimidinoquinolines. In the event, reactions of this type using an excess of formaldehyde in the presence of triethylamine have led to the formation of spiro compounds rather than the expected pyrimidinoquinolines, and we report here the molecular and supramolecular structures of three such compounds, (I)–(III). All of the molecules are chiral, but the compounds studied all crystallize in the centrosymmetric space group P-1 and hence are racemic. The structure of (II) is complicated by the disorder of the –CH₂OH substituent at atom N8, which was modelled using sets of sites, each with an occupancy of 1/2, corresponding to two distinct orientations for this group.

The bond lengths in (I) (Fig. 1 and Table 1) show some unusual values when compared with the typical values for bonds of similar types (Allen et al., 1987). For example, the N3—C4 and C4—-O4 bonds are both long for their types, the C4—C4A and C4A—C8A bonds are too similar in length to be characterized as single and double bonds, respectively, and the C8A—N8 bond, involving a three-coordinate N atom, is much shorter than the C8A—N1 bond, which involves a two-coordinate N atom. These observations, taken together, effectively preclude the polarized form (Ia) as an effective contributor to the overall molecular–electronic structure, instead pointing to the importance of the polarized vinylogous amide form (Ib).

Compounds (II) and (III) (Figs. 2 and 3) both show a much smaller degree of electronic polarization. For example, the difference between the C8A—N1 and C8A—N8 bond lengths (Tables 3 and 5) is much smaller in (II) and (III) than in (I). Hence, for these compounds, the classically localized forms are the most appropriate representations. We also note here the much greater difference between the C2—O2 and O2—C21 distances in (III) (ca 0.11 Å) than between the corresponding C2—S2 and S2—C21 distances in (I) and (II) (ca 0.04 and 0.02 Å, respectively). In each compound, the exocyclic bond angles at atom C2 are very different from 120°.

In each of (I)–(III), the ring containing atoms N1 and N3 is effectively planar, but for the ring containing atom N8, the ring-puckering parameters (Cremer & Pople, 1975) corresponding to the atom sequence N8—C7–C4A—C8A [θ = 129.2 (2)° and ϕ = 304.5 (3)° in (I), θ = 51.3 (3)° and ϕ = 98.5 (3)° in (II), and θ = 126.5 (3)° and ϕ = 283.2 (4)° in (III)] indicate that, in each compound, the conformation of this ring is best described as an envelope form, itself dominated by a combination of boat and chair forms (Evans & Boeyens, 1989). The carbocyclic rings adopt almost perfect chair conformations, with local pseudo-mirror symmetry defined by the plane through the atoms C6, C63, C631 and C632. The conformations of the pendent CH₃—X– substituents [X = S in (I) and (II), and O in (III)] are similar in (I)–(III), while the –CH₂OEt unit in (III) exhibits some unusual torsion angles (Table 5).

The molecules of (I) are linked into a three-dimensional framework by a combination of N—H···O, C—H···O and C—H···π hydrogen bonds (Table 2). Two independent N—H···O hydrogen bonds generate a one-dimensional substructure in the form of a chain of rings; these chains are linked into sheets by the C—H···O hydrogen bonds; and the sheets are linked by C—H···π hydrogen bonds. Atom N3 in the molecule at (x, y, z) acts as a donor to atom O4 in the molecule at (1 − x, 1 − y, 1 − z), so forming a centrosymmetric R²₂(8) ring, centred at (1/2, 1/2, 1/2) (Fig. 4). Similarly, atom N8 at (x, y, z) acts as a donor to atom O65 in the molecule at (-x, 1 − y, −z), forming a centrosymmetry R²₂(12), this time centred at (0, 1/2, 0). The propagation by inversion of these two motifs generates a chain running parallel to the [101] direction. Atom C5 in the molecule at (x, y, z) acts as a hydrogen-bond donor to atom O61 in the molecule at (-x, 2 − y, −z), so forming a third centrosymmetric ring motif, of R²₂(10) type, centred at (0, 1, 0). The combination of this motif with the [101] chains generates a (10–1) sheet (Fig. 4) containing four distinct types of ring, all centrosymmetric; in addition to the R²₂(8), R²₂(10) and R²₂(12) types already described, the sheet also contains R⁶₆(34) rings. Finally, atom C64 in the molecule at (x, y, z), which lies in the sheet passing through (1/2, 1/2, 1/2), acts as a hydrogen-bond donor, via H64A, to the N1/C2/N3/C4/C4A/C8A ring in the molecule at (1 − x, 1 − y, −z), which lies in the sheet passing through (1/2, 1/2, −0.5). The formation of this further centrosymmetric motif (Fig. 5) thus serves to link all of the centrosymmetric sheets into a single framework.

The molecules of (II) are linked by a combination of N—H···O and O—H···O hydrogen bonds (Table 4) into chains, and these chains are linked into sheets by a combination of a C—H···O hydrogen bond and a π–π stacking interaction. The description of the supramolecular aggregation is complicated by the disorder of the pendent –CH₂OH unit. Atom N3 in the molecule at (x, y, z) acts as a hydrogen-bond donor to carbonyl atom O4 in the molecule at (2 − x, 1 − y, 1 − z), so forming a fully ordered R²₂(8) motif centred at (1, 1/2, 1/2). In addition, the partially occupied O8A site at (x, y, z) acts as a donor to carboxyl atom O61 in the molecule at (1 − x, 1 − y, −z). There is also a much longer, and hence presumably weaker, O—H···O interactions involving the alternative atom site O8B as donor, and the same O61 atom as acceptor. Hence, regardless of which site, O8A or O8B, is occupied, there will be two O—H···O linkages between the pair of molecules in question, forming an R²₂(16) ring. If the O8A sites were occupied in both molecules, the ring would be centrosymmetric. At the local level, such pairs of molecules can, in fact, be linked by zero, one or two strong O—H···O hydrogen bonds, with a mean of one such bond. In any event, the combination of the N—H···O and O—H···O hydrogen bonds generates a chain of rings running parallel to the [101] direction (Fig. 6).

Two weaker interactions combine to link the [101] chains into sheets. The N1/C2/N3/C4/C4A/C8A rings in the molecules at (x, y, z) and (1 − x, 1 − y, 1 − z) are parallel, with an interplanar spacing of 3.583 (2) Å; the ring-centroid separation is 3.878 (2) Å, corresponding to a centroid offset of 1.484 (2) Å (Fig. 7). The molecules involved lie in adjacent [101] chains, separated by a unit translation along [100]. This interaction is reinforced by a single C—H···O hydrogen bond; atom C62 in the molecule at (x, y, z) acts as a donor, via H62B, to the partially occupied O8A site in the molecule at (-x, 1 − y, −z) (Fig. 8).

In (III), the molecules are linked into sheets by a combination of N—H···O, C—H···O and C—H···π hydrogen bonds (Table 6). Pairs of N—H···O and of C—H···O hydrogen bonds generate a chain containing two types of centrosymmetric ring, and these chains are linked by C—H···π hydrogen bonds. Amine atom N3 in the molecule at (x, y, z) acts as a hydrogen-bond donor to amide atom O4 in the molecule at (1 − x, 1 − y, 1 − z), thereby generating a centrosymmetric R²₂(8) motif centred at (1/2, 1/2, 1/2). In addition, ring atom C7 at (x, y, z) acts as a donor, via H7B, to the exocyclic atom O81 in the molecule at (3 − x, −y, 1 − z), so forming an R²₂(10) ring centred at (1.5, 0, 1/2). Propagation by inversion of these two hydrogen bonds then generates a chain running parallel to the [2–10] direction in which R²₂(8) and R²₂(10) rings alternate (Fig. 9). Finally, atom C7 in the molecule at (x, y, z), which is part of the [2–10] chain passing through (1/2, 1/2, 1/2), acts as a hydrogen-bond donor, via H7A, to the N1/C2/N3/C4/C4A/C8A ring in the molecule at (2 − x, −y, 1 − z), which itself lies in the [2–10] chain passing through (−0.5, 1/2, 1/2). The resulting centrosymmetric motif (Fig. 10) thus serves to link [2–10] chains into a (001) sheet. Although the structures of both (I) and (III) contain C—H···π hydrogen bonds, they differ in that the donor atoms lie in different rings in the two compounds.

The formation of (I) from the precursor aminopyrimidine, dimedone and two molecules of formaldehyde is straightforward, proceeding via the intermediate (IV) (see the scheme below); we have recently reported the structure of the N³-methyl analogue of (IV) (Low et al., 2004). Further reaction at the secondary amine atom N8 of the primary product of type (A) with another molecule of formaldehyde in the presence of ethanol can lead, via a hydroxymethyl derivative, (B) [cf. compound (II)], to an ethoxymethyl product, (C) [cf. compound (III)].

Experimental top

For the preparation of (I), dimedone (2 mmol), a large excess of an aqueous solution (37% w/w) of formaldehyde (30 mmol formaldehyde) and triethylamine (0.5 mmol) were added to a solution of 6-amino-2-methylsulfanyl-3,4-dihydropyrimidin-4-one (2 mmol) in ethanol, and this mixture was heated under reflux for 90 min. After cooling the mixture, the resulting white product, (I), was filtered off and washed with ethanol (m.p. 563–567 K). Analysis: found: C 55.7, H 5.8, N 12.8, S 10.0%; C₁₅H₁₉N₃O₃S requires: C 13.1, H 6.0, N 13.1, S 10.0%. Compound (II) was an occasional and erratic by-product of this reaction. For the preparation of (III), dimedone (2 mmol) and a large excess of an aqueous solution (37% w/w) of formaldehyde (30 mmol formaldehyde) were added to a solution of 6-amino-2-methoxy-3,4-dihydropyrimidin-4-one (2 mmol) in ethanol, and this mixture was heated under reflux for 90 min. After cooling the mixture, the resulting white product, (III), was filtered off and washed with ethanol (m.p. 533–536 K). For (I) and (II), crystals suitable for single-crystal X-ray diffraction were grown from solutions in wet dimethyl sulfoxide; crystals of (III) suitable for single-crystal X-ray diffraction were grown from a solution in ethanol.

Computing details top

For all compounds, data collection: KappaCCD Server Software (Nonius, 1997); cell refinement: DENZO–SMN (Otwinowski & Minor, 1997); data reduction: DENZO–SMN. Program(s) used to solve structure: OSCAIL (McArdle, 2003) and SHELXS97 (Sheldrick, 1997) for (I); OSCAIL,(McArdle, 2003) and SHELXS97 (Sheldrick, 1997) for (II); SHELXS97 (Sheldrick, 1997) for (III). For all compounds, program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 and PRPKAPPA (Ferguson, 1999).

Figures top

	Fig. 1. The molecule of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. The molecule of (II), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. For clarity, only one orientation of the disordered –CH₂OH substituent is shown.
	Fig. 3. The molecule of (III), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 4. Part of the crystal structure of (I), showing the formation of a (10–1) sheet containing four types of centrosymmetric ring. For clarity, H atoms bonded to atoms not involved in the motifs shown have been omitted. Atoms marked with an asterisk (*), an ampersand (&), a plus sign (+), an 'at' sign (@), a dollar sign () or a hash (#) are at the symmetry positions (1 − x, 1 − y, 1 − z), (1 + x, y, 1 + z), (1 − x, 2 − y, 1 − z), (x, 1 + y, z), (-x, 2 − y, −z) and (-x, 1 − y, −z), respectively.
	Fig. 5. Part of the crystal structure of (I), showing the centrosymmetric linking of the molecules by pairs of C—H···π hydrogen bonds. For clarity, the H atoms bonded to atoms not involved in the motif shown have been omitted. Atoms marked with an asterisk (*) are at the symmetry position (1 − x, 1 − y, −z).
	Fig. 6. A stereoview of part of the crystal structure of (II), showing the formation of a chain of rings along [101]. For clarity, H atoms bonded to C atoms have been omitted, and only one orientation of the disordered hydroxymethyl group is shown.
	Fig. 7. Part of the crystal structure of (II), showing the π–π stacking interaction that links the [101] chains into sheets. For clarity, H atoms bonded to C atoms have been omitted, the unit-cell box has been omitted and only one orientation of the disordered hydroxymethyl group is shown.
	Fig. 8. A stereoview of part of the crystal structure of (II), showing the action of the C—H···O hydrogen bond in linking adjacent [101] chains. For clarity, H atoms bonded to C atoms but not involved in the motif shown have been omitted, and only one orientation of the disordered hydroxymethyl group is shown.
	Fig. 9. Part of the crystal structure of (III), showing the formation of a [2–10] chain of centrosymmetric R²₂(8) and R²₂(10) rings. For clarity, H atoms bonded to atoms not involved in the motif shown have been omitted. Atoms marked with an asterisk (*), a hash (#) or a dollar sign () are at the symmetry positions (1 − x, 1 − y, 1 − z), (3 − x, −y, 1 − z) and (−2 + x, 1 + y, z), respectively.
	Fig. 10. Part of the crystal structure of (III), showing the centrosymmetric linking of the molecules by pairs of C—H···π hydrogen bonds. For clarity, H atoms bonded to atoms not involved in the motif shown have been omitted. Atoms marked with an asterisk (*) are at the symmetry position (2 − x, −y, 1 − z).

(I) 4',4'-Dimethyl-2-methylsulfanyl-3,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidine- 6-spiro-1'-cyclohexane-2',4,6'-trione top

Crystal data top

C₁₅H₁₉N₃O₃S	Z = 2
M_r = 321.39	F(000) = 340
Triclinic, P1	D_x = 1.404 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.8990 (3) Å	Cell parameters from 3462 reflections
b = 10.0386 (3) Å	θ = 3.2–27.5°
c = 10.0500 (3) Å	µ = 0.23 mm⁻¹
α = 74.938 (2)°	T = 120 K
β = 84.271 (2)°	Block, colourless
γ = 81.842 (2)°	0.42 × 0.38 × 0.20 mm
V = 760.10 (4) Å³

Data collection top

Nonius KappaCCD diffractometer	3462 independent reflections
Radiation source: rotating anode	2923 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.057
ϕ scans, and ω scans with κ offsets	θ_max = 27.5°, θ_min = 3.2°
Absorption correction: multi-scan (SORTAV; Blessing, 1995, 1997)	h = −10→10
T_min = 0.921, T_max = 0.956	k = −12→12
15364 measured reflections	l = −12→13

Refinement top

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)] = 0.046	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.125	H-atom parameters constrained
S = 1.04	w = 1/[σ²(F_o²) + (0.0595P)² + 0.5301P] where P = (F_o² + 2F_c²)/3
3462 reflections	(Δ/σ)_max < 0.001
202 parameters	Δρ_max = 1.00 e Å⁻³
0 restraints	Δρ_min = −0.42 e Å⁻³

Crystal data top

C₁₅H₁₉N₃O₃S	γ = 81.842 (2)°
M_r = 321.39	V = 760.10 (4) Å³
Triclinic, P1	Z = 2
a = 7.8990 (3) Å	Mo Kα radiation
b = 10.0386 (3) Å	µ = 0.23 mm⁻¹
c = 10.0500 (3) Å	T = 120 K
α = 74.938 (2)°	0.42 × 0.38 × 0.20 mm
β = 84.271 (2)°

Data collection top

Nonius KappaCCD diffractometer	3462 independent reflections
Absorption correction: multi-scan (SORTAV; Blessing, 1995, 1997)	2923 reflections with I > 2σ(I)
T_min = 0.921, T_max = 0.956	R_int = 0.057
15364 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.046	0 restraints
wR(F²) = 0.125	H-atom parameters constrained
S = 1.04	Δρ_max = 1.00 e Å⁻³
3462 reflections	Δρ_min = −0.42 e Å⁻³
202 parameters

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
S2	0.15187 (6)	0.24922 (5)	0.56484 (5)	0.02612 (15)
O4	0.46653 (17)	0.64675 (14)	0.36030 (13)	0.0279 (3)
O61	0.05306 (17)	0.96763 (14)	−0.15486 (15)	0.0331 (3)
O65	0.28955 (18)	0.55478 (14)	−0.09297 (15)	0.0323 (3)
N1	0.07802 (19)	0.43116 (16)	0.32602 (16)	0.0244 (3)
N3	0.31142 (19)	0.46290 (15)	0.43867 (15)	0.0233 (3)
N8	0.0050 (2)	0.58608 (17)	0.12273 (16)	0.0273 (4)
C2	0.1785 (2)	0.39542 (18)	0.42755 (18)	0.0222 (4)
C4	0.3459 (2)	0.58565 (18)	0.34291 (18)	0.0216 (4)
C4A	0.2356 (2)	0.63152 (18)	0.23395 (18)	0.0209 (4)
C5	0.2533 (2)	0.76576 (18)	0.12915 (18)	0.0227 (4)
C6	0.1928 (2)	0.75976 (18)	−0.01135 (18)	0.0223 (4)
C7	0.0142 (2)	0.71174 (19)	0.01191 (19)	0.0256 (4)
C8A	0.1081 (2)	0.55127 (19)	0.22779 (18)	0.0226 (4)
C21	−0.0302 (2)	0.1891 (2)	0.5149 (2)	0.0291 (4)
C61	0.1869 (2)	0.90528 (19)	−0.10925 (18)	0.0240 (4)
C62	0.3564 (2)	0.96031 (18)	−0.14977 (19)	0.0250 (4)
C63	0.4792 (2)	0.86132 (19)	−0.22051 (19)	0.0249 (4)
C64	0.4979 (2)	0.71366 (19)	−0.1225 (2)	0.0260 (4)
C65	0.3253 (2)	0.66308 (18)	−0.07575 (18)	0.0243 (4)
C631	0.6538 (3)	0.9146 (2)	−0.2529 (2)	0.0335 (4)
C632	0.4043 (3)	0.8563 (2)	−0.35318 (19)	0.0294 (4)
H21A	−0.1256	0.2642	0.5013	0.044*
H21B	−0.0645	0.1097	0.5875	0.044*
H21C	0.0002	0.1606	0.4285	0.044*
H3	0.3806	0.4296	0.5062	0.028*
H5A	0.3746	0.7838	0.1174	0.027*
H5B	0.1837	0.8428	0.1615	0.027*
H7A	−0.0703	0.7868	0.0343	0.031*
H7B	−0.0171	0.6944	−0.0746	0.031*
H8	−0.0872	0.5443	0.1285	0.033*
H62A	0.4072	0.9689	−0.0667	0.030*
H62B	0.3397	1.0538	−0.2139	0.030*
H63A	0.7317	0.8529	−0.2990	0.050*
H63B	0.7008	0.9164	−0.1668	0.050*
H63C	0.6412	1.0087	−0.3136	0.050*
H63D	0.3819	0.9509	−0.4116	0.044*
H63E	0.2968	0.8146	−0.3303	0.044*
H63F	0.4860	0.8003	−0.4028	0.044*
H64A	0.5686	0.6487	−0.1709	0.031*
H64B	0.5577	0.7147	−0.0409	0.031*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S2	0.0244 (2)	0.0256 (3)	0.0252 (2)	−0.00489 (18)	−0.00546 (17)	0.00175 (17)
O4	0.0283 (7)	0.0269 (7)	0.0275 (7)	−0.0075 (5)	−0.0132 (5)	0.0015 (5)
O61	0.0260 (7)	0.0301 (7)	0.0347 (8)	0.0065 (6)	−0.0093 (6)	0.0043 (6)
O65	0.0327 (7)	0.0239 (7)	0.0405 (8)	−0.0050 (6)	−0.0044 (6)	−0.0069 (6)
N1	0.0208 (8)	0.0267 (8)	0.0240 (8)	−0.0027 (6)	−0.0058 (6)	−0.0017 (6)
N3	0.0221 (7)	0.0235 (8)	0.0219 (7)	−0.0023 (6)	−0.0091 (6)	0.0010 (6)
N8	0.0228 (8)	0.0307 (9)	0.0263 (8)	−0.0077 (6)	−0.0101 (6)	0.0022 (6)
C2	0.0206 (8)	0.0219 (9)	0.0225 (8)	−0.0019 (7)	−0.0035 (7)	−0.0023 (7)
C4	0.0203 (8)	0.0216 (8)	0.0215 (8)	−0.0007 (6)	−0.0041 (6)	−0.0028 (6)
C4A	0.0188 (8)	0.0222 (8)	0.0201 (8)	0.0001 (6)	−0.0052 (6)	−0.0021 (7)
C5	0.0220 (8)	0.0230 (9)	0.0214 (8)	−0.0004 (7)	−0.0069 (7)	−0.0018 (7)
C6	0.0202 (8)	0.0216 (9)	0.0225 (9)	0.0007 (7)	−0.0063 (7)	−0.0008 (7)
C7	0.0244 (9)	0.0254 (9)	0.0248 (9)	−0.0008 (7)	−0.0096 (7)	−0.0004 (7)
C8A	0.0182 (8)	0.0259 (9)	0.0218 (8)	−0.0001 (7)	−0.0046 (6)	−0.0026 (7)
C21	0.0258 (9)	0.0288 (10)	0.0322 (10)	−0.0073 (7)	−0.0007 (8)	−0.0049 (8)
C61	0.0256 (9)	0.0234 (9)	0.0204 (8)	0.0032 (7)	−0.0063 (7)	−0.0025 (7)
C62	0.0279 (9)	0.0213 (9)	0.0238 (9)	−0.0011 (7)	−0.0085 (7)	−0.0002 (7)
C63	0.0223 (9)	0.0266 (9)	0.0239 (9)	−0.0027 (7)	−0.0049 (7)	−0.0017 (7)
C64	0.0216 (9)	0.0250 (9)	0.0289 (9)	0.0017 (7)	−0.0050 (7)	−0.0033 (7)
C65	0.0261 (9)	0.0217 (9)	0.0219 (8)	0.0010 (7)	−0.0069 (7)	0.0003 (7)
C631	0.0262 (10)	0.0396 (12)	0.0349 (11)	−0.0091 (8)	−0.0030 (8)	−0.0064 (9)
C632	0.0278 (10)	0.0356 (11)	0.0239 (9)	−0.0060 (8)	−0.0037 (7)	−0.0041 (8)

Geometric parameters (Å, º) top

N1—C2	1.300 (2)	C6—C61	1.532 (2)
C2—N3	1.356 (2)	C6—C65	1.536 (2)
N3—C4	1.395 (2)	C61—C62	1.499 (3)
C4—C4A	1.409 (2)	C62—C63	1.546 (3)
C4A—C8A	1.391 (2)	C62—H62A	0.99
C8A—N1	1.379 (2)	C62—H62B	0.99
C4—O4	1.253 (2)	C63—C631	1.525 (3)
C8A—N8	1.342 (2)	C63—C632	1.527 (3)
C7—N8	1.455 (2)	C63—C64	1.548 (3)
C2—S2	1.7547 (18)	C631—H63A	0.98
S2—C21	1.7983 (19)	C631—H63B	0.98
C61—O61	1.216 (2)	C631—H63C	0.98
C65—O65	1.219 (2)	C632—H63D	0.98
C21—H21A	0.98	C632—H63E	0.98
C21—H21B	0.98	C632—H63F	0.98
C21—H21C	0.98	C64—C65	1.511 (3)
N3—H3	0.88	C64—H64A	0.99
C4A—C5	1.494 (2)	C64—H64B	0.99
C5—C6	1.554 (2)	C7—H7A	0.99
C5—H5A	0.99	C7—H7B	0.99
C5—H5B	0.99	N8—H8	0.88
C6—C7	1.532 (2)

C2—N1—C8A	115.44 (15)	H62A—C62—H62B	108.2
N1—C2—N3	125.04 (16)	C631—C63—C632	110.35 (16)
N1—C2—S2	121.25 (14)	C631—C63—C62	109.14 (16)
N3—C2—S2	113.71 (13)	C632—C63—C62	108.96 (15)
C2—S2—C21	100.96 (9)	C631—C63—C64	109.67 (15)
S2—C21—H21A	109.5	C632—C63—C64	109.27 (15)
S2—C21—H21B	109.5	C62—C63—C64	109.43 (15)
H21A—C21—H21B	109.5	C63—C631—H63A	109.5
S2—C21—H21C	109.5	C63—C631—H63B	109.5
H21A—C21—H21C	109.5	H63A—C631—H63B	109.5
H21B—C21—H21C	109.5	C63—C631—H63C	109.5
C2—N3—C4	121.61 (15)	H63A—C631—H63C	109.5
C2—N3—H3	120.9	H63B—C631—H63C	109.5
C4—N3—H3	117.5	C63—C632—H63D	109.5
O4—C4—N3	119.22 (15)	C63—C632—H63E	109.5
O4—C4—C4A	125.53 (16)	H63D—C632—H63E	109.5
N3—C4—C4A	115.24 (15)	C63—C632—H63F	109.5
C8A—C4A—C4	118.83 (16)	H63D—C632—H63F	109.5
C8A—C4A—C5	120.88 (15)	H63E—C632—H63F	109.5
C4—C4A—C5	120.27 (15)	C65—C64—C63	111.36 (14)
C4A—C5—C6	110.13 (14)	C65—C64—H64A	109.4
C4A—C5—H5A	109.6	C63—C64—H64A	109.4
C6—C5—H5A	109.6	C65—C64—H64B	109.4
C4A—C5—H5B	109.6	C63—C64—H64B	109.4
C6—C5—H5B	109.6	H64A—C64—H64B	108.0
H5A—C5—H5B	108.1	O65—C65—C64	122.40 (17)
C7—C6—C61	110.16 (14)	O65—C65—C6	121.37 (17)
C7—C6—C65	112.50 (15)	C64—C65—C6	116.15 (15)
C61—C6—C65	107.40 (14)	N8—C7—C6	112.53 (14)
C7—C6—C5	109.13 (14)	N8—C7—H7A	109.1
C61—C6—C5	108.56 (14)	C6—C7—H7A	109.1
C65—C6—C5	109.02 (14)	N8—C7—H7B	109.1
O61—C61—C62	123.16 (17)	C6—C7—H7B	109.1
O61—C61—C6	121.12 (17)	H7A—C7—H7B	107.8
C62—C61—C6	115.64 (14)	C8A—N8—C7	122.57 (15)
C61—C62—C63	110.06 (15)	C8A—N8—H8	120.0
C61—C62—H62A	109.6	C7—N8—H8	115.9
C63—C62—H62A	109.6	N8—C8A—N1	114.84 (16)
C61—C62—H62B	109.6	N8—C8A—C4A	121.46 (16)
C63—C62—H62B	109.6	N1—C8A—C4A	123.70 (16)

C8A—N1—C2—N3	−3.3 (3)	C4A—C5—C6—C65	−71.82 (18)
C8A—N1—C2—S2	177.39 (13)	C7—C6—C61—O61	1.4 (2)
N1—C2—S2—C21	−0.46 (18)	C65—C6—C61—O61	124.28 (19)
N3—C2—S2—C21	−179.84 (14)	C5—C6—C61—O61	−117.99 (19)
N1—C2—N3—C4	4.2 (3)	C7—C6—C61—C62	−175.34 (15)
S2—C2—N3—C4	−176.43 (13)	C5—C6—C61—C62	65.23 (19)
C2—N3—C4—O4	177.52 (16)	O61—C61—C62—C63	−118.25 (19)
C2—N3—C4—C4A	−1.3 (2)	C61—C62—C63—C631	−176.60 (15)
O4—C4—C4A—C8A	179.34 (17)	C61—C62—C63—C632	62.84 (19)
N3—C4—C4A—C8A	−2.0 (2)	C631—C63—C64—C65	173.96 (16)
O4—C4—C4A—C5	−2.1 (3)	C632—C63—C64—C65	−65.0 (2)
N3—C4—C4A—C5	176.63 (15)	C63—C64—C65—O65	123.80 (19)
C4—C4A—C5—C6	151.19 (16)	C7—C6—C65—O65	−6.0 (2)
C4A—C5—C6—C7	51.41 (18)	C61—C6—C65—O65	−127.42 (18)
C5—C6—C7—N8	−50.4 (2)	C5—C6—C65—O65	115.15 (18)
C6—C7—N8—C8A	26.8 (3)	C7—C6—C65—C64	170.96 (15)
C7—N8—C8A—C4A	−2.5 (3)	C5—C6—C65—C64	−67.85 (19)
N8—C8A—C4A—C5	4.8 (3)	C61—C6—C7—N8	−169.50 (15)
C8A—C4A—C5—C6	−30.3 (2)	C65—C6—C7—N8	70.72 (19)
C6—C61—C62—C63	58.5 (2)	C7—N8—C8A—N1	177.95 (16)
C61—C62—C63—C64	−56.58 (18)	C2—N1—C8A—N8	179.23 (16)
C62—C63—C64—C65	54.3 (2)	C2—N1—C8A—C4A	−0.3 (3)
C63—C64—C65—C6	−53.2 (2)	C4—C4A—C8A—N8	−176.60 (17)
C64—C65—C6—C61	49.58 (19)	C4—C4A—C8A—N1	2.9 (3)
C65—C6—C61—C62	−52.5 (2)	C5—C4A—C8A—N1	−175.72 (16)
C4A—C5—C6—C61	171.49 (14)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···O4ⁱ	0.88	1.84	2.715 (2)	176
N8—H8···O65ⁱⁱ	0.88	2.10	2.965 (2)	166
C5—H5B···O61ⁱⁱⁱ	0.99	2.46	3.389 (2)	155
C64—H64A···Cg1^iv	0.99	2.87	3.854 (2)	173

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

(II) 8-Hydroxymethyl-4',4'-dimethyl-2-methylsulfanyl-3,4,5,6,7,8- hexahydropyrido[2,3-d]pyrimidine-6-spiro-1'-cyclohexane-2',4,6'-trione top

Crystal data top

C₁₆H₂₁N₃O₄S	Z = 2
M_r = 351.42	F(000) = 372
Triclinic, P1	D_x = 1.435 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 6.6682 (2) Å	Cell parameters from 3737 reflections
b = 11.0319 (3) Å	θ = 3.2–27.5°
c = 12.3449 (4) Å	µ = 0.23 mm⁻¹
α = 109.2678 (18)°	T = 120 K
β = 99.8329 (18)°	Plate, colourless
γ = 101.227 (2)°	0.15 × 0.10 × 0.03 mm
V = 813.32 (5) Å³

Data collection top

Nonius KappaCCD diffractometer	3737 independent reflections
Radiation source: rotating anode	2502 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.047
ϕ scans, and ω scans with κ offsets	θ_max = 27.5°, θ_min = 3.2°
Absorption correction: multi-scan (SORTAV; Blessing, 1995, 1997)	h = −8→8
T_min = 0.976, T_max = 0.994	k = −14→14
18379 measured reflections	l = −15→16

Refinement top

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)] = 0.051	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.140	H-atom parameters constrained
S = 1.03	w = 1/[σ²(F_o²) + (0.066P)² + 0.2491P] where P = (F_o² + 2F_c²)/3
3737 reflections	(Δ/σ)_max < 0.001
238 parameters	Δρ_max = 0.28 e Å⁻³
4 restraints	Δρ_min = −0.41 e Å⁻³

Crystal data top

C₁₆H₂₁N₃O₄S	γ = 101.227 (2)°
M_r = 351.42	V = 813.32 (5) Å³
Triclinic, P1	Z = 2
a = 6.6682 (2) Å	Mo Kα radiation
b = 11.0319 (3) Å	µ = 0.23 mm⁻¹
c = 12.3449 (4) Å	T = 120 K
α = 109.2678 (18)°	0.15 × 0.10 × 0.03 mm
β = 99.8329 (18)°

Data collection top

Nonius KappaCCD diffractometer	3737 independent reflections
Absorption correction: multi-scan (SORTAV; Blessing, 1995, 1997)	2502 reflections with I > 2σ(I)
T_min = 0.976, T_max = 0.994	R_int = 0.047
18379 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.051	4 restraints
wR(F²) = 0.140	H-atom parameters constrained
S = 1.03	Δρ_max = 0.28 e Å⁻³
3737 reflections	Δρ_min = −0.41 e Å⁻³
238 parameters

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
S2	0.73487 (11)	0.77931 (5)	0.56516 (5)	0.0559 (2)
O4	0.8658 (3)	0.35113 (16)	0.36896 (15)	0.0701 (6)
O8A	0.0777 (5)	0.5505 (3)	0.0734 (3)	0.0474 (8)	0.50
O8B	0.1860 (5)	0.6134 (4)	0.1656 (3)	0.0500 (8)	0.50
O61	0.6178 (2)	0.37648 (14)	0.03689 (14)	0.0461 (4)
O65	0.2484 (2)	−0.00235 (13)	0.00947 (12)	0.0382 (4)
N1	0.4772 (3)	0.59074 (17)	0.36624 (16)	0.0460 (5)
N3	0.7797 (4)	0.54542 (17)	0.45024 (15)	0.0522 (6)
N8	0.2429 (3)	0.43269 (17)	0.19453 (17)	0.0472 (5)
C2	0.6503 (4)	0.6233 (2)	0.44750 (18)	0.0431 (6)
C4	0.7391 (4)	0.4187 (2)	0.36314 (19)	0.0491 (6)
C4A	0.5490 (3)	0.37791 (19)	0.27379 (17)	0.0393 (5)
C5	0.4922 (3)	0.24252 (19)	0.17519 (17)	0.0374 (5)
C6	0.3324 (3)	0.23534 (18)	0.06839 (16)	0.0325 (5)
C7	0.1552 (3)	0.29491 (19)	0.11179 (18)	0.0393 (5)
C8A	0.4264 (3)	0.4653 (2)	0.27876 (18)	0.0405 (5)
C21	0.5183 (5)	0.8446 (2)	0.5328 (2)	0.0681 (8)
C61	0.4339 (3)	0.31261 (18)	−0.00039 (18)	0.0342 (5)
C62	0.3010 (3)	0.29784 (19)	−0.11717 (18)	0.0369 (5)
C63	0.2179 (4)	0.1500 (2)	−0.19984 (18)	0.0427 (6)
C64	0.0954 (4)	0.0723 (2)	−0.13757 (17)	0.0414 (5)
C65	0.2261 (3)	0.09007 (19)	−0.01856 (17)	0.0338 (5)
C81A	0.117 (2)	0.5262 (14)	0.1814 (11)	0.0454 (15)	0.50
C81B	0.106 (2)	0.5204 (14)	0.2135 (11)	0.0454 (15)	0.50
C631	0.4024 (5)	0.0939 (2)	−0.2260 (2)	0.0611 (8)
C632	0.0690 (5)	0.1399 (2)	−0.3135 (2)	0.0606 (8)
H3	0.8944	0.5750	0.5090	0.063*
H5A	0.4327	0.1731	0.2040	0.045*
H5B	0.6214	0.2246	0.1516	0.045*
H7A	0.0497	0.2911	0.0429	0.047*
H7B	0.0825	0.2414	0.1513	0.047*
H8A	0.1924	0.5880	0.0643	0.057*	0.50
H8B	0.2429	0.5775	0.1123	0.060*	0.50
H21A	0.4913	0.8373	0.4500	0.102*
H21B	0.5519	0.9385	0.5852	0.102*
H21C	0.3922	0.7940	0.5452	0.102*
H62A	0.3862	0.3478	−0.1548	0.044*
H62B	0.1803	0.3358	−0.1042	0.044*
H63A	0.0162	0.0463	−0.3680	0.091*
H63B	0.1458	0.1922	−0.3514	0.091*
H63C	−0.0503	0.1745	−0.2939	0.091*
H63D	0.4905	0.0976	−0.1521	0.092*
H63E	0.4871	0.1468	−0.2606	0.092*
H63F	0.3489	0.0011	−0.2820	0.092*
H64A	−0.0325	0.1029	−0.1270	0.050*
H64B	0.0489	−0.0237	−0.1887	0.050*
H81A	−0.0222	0.4938	0.1949	0.054*	0.50
H81B	0.1877	0.6134	0.2467	0.054*	0.50
H81C	−0.0428	0.4713	0.1713	0.054*	0.50
H81D	0.1163	0.5646	0.2990	0.054*	0.50

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S2	0.0910 (5)	0.0289 (3)	0.0278 (3)	−0.0058 (3)	0.0162 (3)	−0.0023 (2)
O4	0.1007 (15)	0.0337 (9)	0.0459 (10)	0.0158 (10)	−0.0274 (10)	0.0014 (8)
O8A	0.0405 (18)	0.053 (2)	0.050 (2)	0.0121 (15)	0.0125 (16)	0.0217 (17)
O8B	0.0458 (19)	0.052 (2)	0.049 (2)	0.0127 (16)	0.0105 (17)	0.0153 (17)
O61	0.0399 (9)	0.0370 (8)	0.0523 (9)	−0.0035 (7)	0.0111 (7)	0.0135 (7)
O65	0.0424 (8)	0.0238 (7)	0.0403 (8)	0.0019 (6)	0.0094 (6)	0.0064 (6)
N1	0.0558 (12)	0.0291 (9)	0.0366 (10)	−0.0028 (8)	0.0171 (9)	−0.0030 (8)
N3	0.0835 (15)	0.0260 (9)	0.0257 (9)	−0.0010 (10)	−0.0074 (9)	0.0025 (7)
N8	0.0381 (10)	0.0312 (9)	0.0515 (11)	0.0037 (8)	0.0110 (9)	−0.0074 (8)
C2	0.0669 (15)	0.0244 (10)	0.0259 (10)	−0.0048 (10)	0.0126 (11)	0.0033 (8)
C4	0.0777 (17)	0.0262 (11)	0.0285 (11)	0.0008 (11)	−0.0020 (11)	0.0069 (9)
C4A	0.0529 (13)	0.0263 (10)	0.0270 (10)	−0.0017 (9)	0.0091 (9)	0.0029 (8)
C5	0.0474 (12)	0.0257 (10)	0.0285 (10)	0.0003 (9)	0.0057 (9)	0.0042 (8)
C6	0.0375 (11)	0.0226 (9)	0.0281 (10)	−0.0009 (8)	0.0084 (8)	0.0026 (8)
C7	0.0401 (12)	0.0291 (10)	0.0347 (11)	−0.0021 (9)	0.0117 (9)	−0.0002 (9)
C8A	0.0491 (13)	0.0275 (10)	0.0313 (11)	−0.0034 (9)	0.0142 (10)	−0.0004 (8)
C21	0.099 (2)	0.0377 (13)	0.0507 (15)	0.0092 (14)	0.0320 (15)	−0.0057 (11)
C61	0.0409 (12)	0.0189 (9)	0.0384 (11)	0.0032 (8)	0.0149 (9)	0.0054 (8)
C62	0.0459 (12)	0.0252 (10)	0.0361 (11)	0.0023 (9)	0.0139 (9)	0.0095 (8)
C63	0.0663 (15)	0.0267 (10)	0.0290 (10)	0.0023 (10)	0.0178 (10)	0.0057 (8)
C64	0.0556 (14)	0.0267 (10)	0.0272 (10)	−0.0070 (9)	0.0069 (9)	0.0038 (8)
C65	0.0379 (11)	0.0248 (10)	0.0309 (10)	−0.0023 (8)	0.0146 (9)	0.0039 (8)
C81A	0.0417 (18)	0.0393 (16)	0.045 (6)	0.0019 (15)	0.029 (4)	−0.001 (3)
C81B	0.0417 (18)	0.0393 (16)	0.045 (6)	0.0019 (15)	0.029 (4)	−0.001 (3)
C631	0.095 (2)	0.0367 (12)	0.0580 (16)	0.0164 (13)	0.0463 (15)	0.0136 (12)
C632	0.096 (2)	0.0394 (13)	0.0308 (12)	−0.0069 (13)	0.0099 (12)	0.0104 (10)

Geometric parameters (Å, º) top

N1—C2	1.294 (3)	C63—C632	1.531 (3)
C2—N3	1.334 (3)	C63—C64	1.540 (3)
N3—C4	1.395 (3)	C631—H63D	0.98
C4—C4A	1.414 (3)	C631—H63E	0.98
C4A—C8A	1.374 (3)	C631—H63F	0.98
C8A—N1	1.379 (3)	C632—H63A	0.98
C4—O4	1.239 (3)	C632—H63B	0.98
C8A—N8	1.362 (3)	C632—H63C	0.98
C7—N8	1.456 (2)	C64—C65	1.504 (3)
C2—S2	1.756 (2)	C64—H64A	0.99
S2—C21	1.779 (3)	C64—H64B	0.99
C61—O61	1.212 (2)	C7—H7A	0.99
C65—O65	1.206 (2)	C7—H7B	0.99
C21—H21A	0.98	N8—C81B	1.445 (8)
C21—H21B	0.98	N8—C81A	1.482 (7)
C21—H21C	0.98	C81A—O8A	1.436 (8)
N3—H3	0.88	C81A—H81A	0.99
C6—C5	1.516 (3)	C81A—H81B	0.99
C6—C61	1.535 (3)	O8A—H8A	0.84
C6—C65	1.544 (2)	C81B—O8B	1.407 (9)
C6—C7	1.550 (3)	C81B—H81C	0.99
C61—C62	1.498 (3)	C81B—H81D	0.99
C62—C63	1.538 (3)	O8B—H8B	0.84
C62—H62A	0.99	C4A—C5	1.509 (3)
C62—H62B	0.99	C5—H5A	0.99
C63—C631	1.517 (4)	C5—H5B	0.99

C2—N1—C8A	115.9 (2)	H63A—C632—H63C	109.5
N1—C2—N3	124.60 (19)	H63B—C632—H63C	109.5
N1—C2—S2	121.14 (19)	C65—C64—C63	112.38 (17)
N3—C2—S2	114.25 (17)	C65—C64—H64A	109.1
C2—S2—C21	99.74 (12)	C63—C64—H64A	109.1
S2—C21—H21A	109.5	C65—C64—H64B	109.1
S2—C21—H21B	109.5	C63—C64—H64B	109.1
H21A—C21—H21B	109.5	H64A—C64—H64B	107.9
S2—C21—H21C	109.5	O65—C65—C64	122.99 (17)
H21A—C21—H21C	109.5	O65—C65—C6	120.79 (18)
H21B—C21—H21C	109.5	C64—C65—C6	116.22 (18)
C2—N3—C4	122.2 (2)	N8—C7—C6	110.54 (16)
C2—N3—H3	118.9	N8—C7—H7A	109.5
C4—N3—H3	118.9	C6—C7—H7A	109.5
O4—C4—N3	119.6 (2)	N8—C7—H7B	109.5
O4—C4—C4A	125.2 (2)	C6—C7—H7B	109.5
N3—C4—C4A	115.1 (2)	H7A—C7—H7B	108.1
C5—C6—C61	111.79 (16)	C8A—N8—C81B	118.4 (7)
C5—C6—C65	111.91 (17)	C8A—N8—C7	119.01 (19)
C61—C6—C65	107.97 (15)	C81B—N8—C7	119.2 (7)
C5—C6—C7	108.64 (16)	C8A—N8—C81A	125.2 (7)
C61—C6—C7	109.28 (17)	C7—N8—C81A	115.8 (7)
C65—C6—C7	107.13 (15)	O8A—C81A—N8	120.5 (6)
O61—C61—C62	122.43 (19)	O8A—C81A—H81A	107.2
O61—C61—C6	120.23 (19)	N8—C81A—H81A	107.2
C62—C61—C6	117.22 (16)	O8A—C81A—H81B	107.2
C61—C62—C63	110.53 (17)	N8—C81A—H81B	107.2
C61—C62—H62A	109.5	H81A—C81A—H81B	106.8
C63—C62—H62A	109.5	O8B—C81B—N8	102.7 (6)
C61—C62—H62B	109.5	O8B—C81B—H81C	111.2
C63—C62—H62B	109.5	N8—C81B—H81C	111.2
H62A—C62—H62B	108.1	O8B—C81B—H81D	111.2
C631—C63—C632	111.5 (2)	N8—C81B—H81D	111.2
C631—C63—C62	109.62 (19)	H81C—C81B—H81D	109.1
C632—C63—C62	108.29 (19)	C81B—O8B—H8B	109.5
C631—C63—C64	108.88 (19)	C8A—C4A—C4	118.29 (19)
C632—C63—C64	109.54 (18)	C8A—C4A—C5	122.70 (19)
C62—C63—C64	108.98 (16)	C4—C4A—C5	119.0 (2)
C63—C631—H63D	109.5	C4A—C5—C6	111.07 (18)
C63—C631—H63E	109.5	C4A—C5—H5A	109.4
H63D—C631—H63E	109.5	C6—C5—H5A	109.4
C63—C631—H63F	109.5	C4A—C5—H5B	109.4
H63D—C631—H63F	109.5	C6—C5—H5B	109.4
H63E—C631—H63F	109.5	H5A—C5—H5B	108.0
C63—C632—H63A	109.5	N8—C8A—C4A	121.15 (18)
C63—C632—H63B	109.5	N8—C8A—N1	115.0 (2)
H63A—C632—H63B	109.5	C4A—C8A—N1	123.9 (2)
C63—C632—H63C	109.5

C8A—N1—C2—N3	1.0 (3)	C6—C61—C62—C63	−55.9 (2)
C8A—N1—C2—S2	−179.61 (15)	C61—C62—C63—C64	56.3 (2)
N1—C2—S2—C21	3.4 (2)	C62—C63—C64—C65	−55.6 (3)
N3—C2—S2—C21	−177.13 (17)	C63—C64—C65—C6	52.5 (2)
N1—C2—N3—C4	0.2 (3)	C64—C65—C6—C61	−45.7 (2)
S2—C2—N3—C4	−179.20 (17)	C65—C6—C61—C62	48.1 (2)
C2—N3—C4—O4	179.0 (2)	C6—C7—N8—C81B	158.5 (4)
C2—N3—C4—C4A	−1.4 (3)	C7—N8—C81B—O8B	−113.3 (9)
C5—C6—C61—O61	−4.5 (3)	C61—C6—C7—N8	−63.2 (2)
C65—C6—C61—O61	−128.0 (2)	C65—C6—C7—N8	−179.91 (17)
C7—C6—C61—O61	115.8 (2)	C8A—N8—C81A—O8A	120.2 (11)
C5—C6—C61—C62	171.59 (17)	C81B—N8—C81A—O8A	−168 (6)
C7—C6—C61—C62	−68.1 (2)	C8A—N8—C81B—O8B	87.5 (8)
O61—C61—C62—C63	120.1 (2)	C81A—N8—C81B—O8B	−31 (4)
C61—C62—C63—C631	−62.7 (2)	O4—C4—C4A—C8A	−179.1 (2)
C61—C62—C63—C632	175.42 (18)	N3—C4—C4A—C8A	1.4 (3)
C631—C63—C64—C65	64.0 (2)	O4—C4—C4A—C5	−0.9 (4)
C632—C63—C64—C65	−173.88 (19)	N3—C4—C4A—C5	179.61 (18)
C63—C64—C65—O65	−127.7 (2)	C4—C4A—C5—C6	−159.99 (19)
C5—C6—C65—O65	11.1 (3)	C61—C6—C5—C4A	74.5 (2)
C61—C6—C65—O65	134.5 (2)	C65—C6—C5—C4A	−164.23 (16)
C7—C6—C65—O65	−107.9 (2)	C81B—N8—C8A—C4A	171.3 (5)
C5—C6—C65—C64	−169.11 (17)	C81A—N8—C8A—C4A	−170.2 (4)
C7—C6—C65—C64	71.9 (2)	C81B—N8—C8A—N1	−9.2 (5)
C4A—C5—C6—C7	−46.1 (2)	C7—N8—C8A—N1	−168.49 (18)
C5—C6—C7—N8	59.0 (2)	C81A—N8—C8A—N1	9.3 (5)
C6—C7—N8—C8A	−42.4 (3)	C4—C4A—C8A—N8	179.14 (19)
C7—N8—C8A—C4A	12.1 (3)	C4—C4A—C8A—N1	−0.3 (3)
N8—C8A—C4A—C5	1.0 (3)	C5—C4A—C8A—N1	−178.39 (18)
C8A—C4A—C5—C6	18.1 (3)	C2—N1—C8A—N8	179.60 (18)
C6—C7—N8—C81A	139.6 (4)	C2—N1—C8A—C4A	−1.0 (3)
C7—N8—C81A—O8A	−61.9 (14)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···O4ⁱ	0.88	1.83	2.709 (3)	176
O8A—H8A···O61ⁱⁱ	0.84	2.00	2.767 (3)	152
O8B—H8B···O61ⁱⁱ	0.84	2.35	3.036 (4)	139
C62—H62B···O8Aⁱⁱⁱ	0.99	2.33	3.314 (4)	173

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

(III) 8-Ethoxymethyl-4',4'-dimethyl-2-methoxy-3,4,5,6,7,8- hexahydropyrido[2,3-d]pyrimidine-6-spiro-1'-cyclohexane-2',4,6'-trione top

Crystal data top

C₁₈H₂₅N₃O₅	Z = 2
M_r = 363.41	F(000) = 388
Triclinic, P1	D_x = 1.344 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.9219 (5) Å	Cell parameters from 4082 reflections
b = 9.9806 (5) Å	θ = 2.9–27.6°
c = 11.3542 (7) Å	µ = 0.10 mm⁻¹
α = 75.662 (3)°	T = 120 K
β = 85.580 (3)°	Prism, colourless
γ = 66.526 (3)°	0.15 × 0.10 × 0.10 mm
V = 898.22 (9) Å³

Data collection top

Nonius KappaCCD diffractometer	4082 independent reflections
Radiation source: rotating anode	2026 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.088
ϕ scans, and ω scans with κ offsets	θ_max = 27.6°, θ_min = 2.9°
Absorption correction: multi-scan (SORTAV; Blessing, 1995, 1997)	h = −11→11
T_min = 0.967, T_max = 0.990	k = −12→12
17797 measured reflections	l = −14→14

Refinement top

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)] = 0.056	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.164	H-atom parameters constrained
S = 0.95	w = 1/[σ²(F_o²) + (0.0803P)²] where P = (F_o² + 2F_c²)/3
4082 reflections	(Δ/σ)_max < 0.001
239 parameters	Δρ_max = 0.30 e Å⁻³
0 restraints	Δρ_min = −0.43 e Å⁻³

Crystal data top

C₁₈H₂₅N₃O₅	γ = 66.526 (3)°
M_r = 363.41	V = 898.22 (9) Å³
Triclinic, P1	Z = 2
a = 8.9219 (5) Å	Mo Kα radiation
b = 9.9806 (5) Å	µ = 0.10 mm⁻¹
c = 11.3542 (7) Å	T = 120 K
α = 75.662 (3)°	0.15 × 0.10 × 0.10 mm
β = 85.580 (3)°

Data collection top

Nonius KappaCCD diffractometer	4082 independent reflections
Absorption correction: multi-scan (SORTAV; Blessing, 1995, 1997)	2026 reflections with I > 2σ(I)
T_min = 0.967, T_max = 0.990	R_int = 0.088
17797 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.056	0 restraints
wR(F²) = 0.164	H-atom parameters constrained
S = 0.95	Δρ_max = 0.30 e Å⁻³
4082 reflections	Δρ_min = −0.43 e Å⁻³
239 parameters

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O2	0.76490 (19)	0.29677 (18)	0.77260 (15)	0.0267 (4)
O4	0.60281 (19)	0.42536 (19)	0.37935 (16)	0.0307 (5)
O61	1.0648 (2)	0.45522 (19)	0.30859 (17)	0.0341 (5)
O65	1.0669 (2)	0.1427 (2)	0.09973 (17)	0.0366 (5)
O81	1.3916 (2)	0.11344 (19)	0.57305 (17)	0.0333 (5)
N1	0.9621 (2)	0.2004 (2)	0.63954 (19)	0.0220 (5)
N3	0.6927 (2)	0.3582 (2)	0.57622 (19)	0.0244 (5)
N8	1.1529 (2)	0.1062 (2)	0.49992 (18)	0.0219 (5)
C2	0.8137 (3)	0.2829 (3)	0.6605 (2)	0.0222 (6)
C4	0.7185 (3)	0.3526 (3)	0.4551 (2)	0.0235 (6)
C4A	0.8788 (3)	0.2631 (3)	0.4273 (2)	0.0214 (6)
C5	0.9216 (3)	0.2579 (3)	0.2974 (2)	0.0250 (6)
C6	1.1047 (3)	0.2140 (3)	0.2781 (2)	0.0226 (6)
C7	1.1958 (3)	0.0750 (3)	0.3809 (2)	0.0230 (6)
C8A	0.9942 (3)	0.1920 (3)	0.5206 (2)	0.0211 (6)
C21	0.8922 (3)	0.2250 (3)	0.8662 (2)	0.0291 (7)
C61	1.1592 (3)	0.3407 (3)	0.2821 (2)	0.0237 (6)
C62	1.3327 (3)	0.3162 (3)	0.2472 (2)	0.0272 (6)
C63	1.3671 (3)	0.2836 (3)	0.1202 (2)	0.0293 (7)
C64	1.3292 (3)	0.1471 (3)	0.1194 (2)	0.0284 (6)
C65	1.1581 (3)	0.1657 (3)	0.1582 (2)	0.0252 (6)
C81	1.2815 (3)	0.0402 (3)	0.5923 (2)	0.0285 (6)
C82	1.3228 (3)	0.2618 (3)	0.5964 (3)	0.0355 (7)
C83	1.3285 (4)	0.2592 (3)	0.7284 (3)	0.0424 (8)
C631	1.5468 (3)	0.2495 (3)	0.0911 (3)	0.0453 (8)
C632	1.2588 (4)	0.4201 (3)	0.0250 (3)	0.0404 (8)
H3	0.5981	0.4209	0.5960	0.029*
H5A	0.8609	0.3578	0.2436	0.030*
H5B	0.8878	0.1841	0.2749	0.030*
H7A	1.1679	−0.0097	0.3748	0.028*
H7B	1.3152	0.0444	0.3708	0.028*
H21A	0.9469	0.1177	0.8677	0.044*
H21B	0.8440	0.2369	0.9454	0.044*
H21C	0.9721	0.2716	0.8489	0.044*
H62A	1.4085	0.2305	0.3077	0.033*
H62B	1.3524	0.4068	0.2479	0.033*
H63A	1.5730	0.3339	0.0974	0.068*
H63B	1.5667	0.2345	0.0083	0.068*
H63C	1.6158	0.1581	0.1489	0.068*
H63D	1.1436	0.4423	0.0443	0.061*
H63E	1.2797	0.3982	−0.0556	0.061*
H63F	1.2837	0.5071	0.0254	0.061*
H64A	1.3444	0.1297	0.0364	0.034*
H64B	1.4080	0.0572	0.1746	0.034*
H81A	1.2320	0.0457	0.6729	0.034*
H81B	1.3426	−0.0673	0.5926	0.034*
H82A	1.2077	0.3126	0.5665	0.043*
H82B	1.3835	0.3214	0.5502	0.043*
H83A	1.2747	0.1952	0.7753	0.064*
H83B	1.2720	0.3616	0.7398	0.064*
H83C	1.4427	0.2192	0.7564	0.064*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O2	0.0216 (10)	0.0335 (10)	0.0220 (11)	−0.0078 (8)	0.0001 (8)	−0.0065 (8)
O4	0.0180 (10)	0.0380 (11)	0.0297 (12)	−0.0032 (8)	−0.0046 (9)	−0.0085 (9)
O61	0.0357 (11)	0.0259 (10)	0.0400 (13)	−0.0113 (9)	0.0090 (9)	−0.0104 (9)
O65	0.0359 (11)	0.0463 (12)	0.0337 (12)	−0.0188 (9)	−0.0001 (9)	−0.0151 (10)
O81	0.0216 (10)	0.0365 (11)	0.0456 (13)	−0.0103 (8)	0.0025 (9)	−0.0186 (9)
N1	0.0173 (12)	0.0218 (11)	0.0253 (13)	−0.0057 (9)	0.0012 (9)	−0.0065 (9)
N3	0.0137 (11)	0.0269 (12)	0.0282 (14)	−0.0018 (9)	0.0016 (10)	−0.0098 (10)
N8	0.0150 (11)	0.0229 (11)	0.0229 (13)	−0.0025 (9)	−0.0008 (9)	−0.0050 (9)
C2	0.0215 (14)	0.0216 (13)	0.0246 (16)	−0.0100 (11)	0.0001 (12)	−0.0044 (11)
C4	0.0199 (14)	0.0253 (14)	0.0266 (17)	−0.0097 (11)	0.0012 (13)	−0.0074 (12)
C4A	0.0165 (13)	0.0222 (13)	0.0246 (15)	−0.0071 (11)	−0.0002 (12)	−0.0050 (11)
C5	0.0199 (14)	0.0251 (13)	0.0274 (16)	−0.0065 (11)	−0.0035 (12)	−0.0049 (12)
C6	0.0189 (13)	0.0256 (14)	0.0222 (15)	−0.0077 (11)	0.0007 (11)	−0.0057 (11)
C7	0.0213 (14)	0.0209 (13)	0.0253 (16)	−0.0071 (11)	0.0022 (12)	−0.0055 (11)
C8A	0.0170 (13)	0.0197 (13)	0.0274 (16)	−0.0080 (11)	0.0025 (12)	−0.0061 (11)
C21	0.0250 (15)	0.0356 (15)	0.0249 (16)	−0.0100 (12)	−0.0002 (12)	−0.0070 (12)
C61	0.0248 (14)	0.0248 (14)	0.0183 (15)	−0.0083 (12)	0.0002 (12)	−0.0017 (11)
C62	0.0260 (15)	0.0263 (14)	0.0292 (17)	−0.0113 (11)	0.0010 (12)	−0.0050 (12)
C63	0.0230 (14)	0.0313 (15)	0.0307 (17)	−0.0098 (12)	0.0036 (13)	−0.0044 (12)
C64	0.0246 (14)	0.0290 (14)	0.0275 (16)	−0.0058 (11)	0.0045 (12)	−0.0092 (12)
C65	0.0255 (15)	0.0200 (14)	0.0278 (16)	−0.0079 (11)	0.0004 (13)	−0.0031 (12)
C81	0.0198 (14)	0.0297 (15)	0.0327 (17)	−0.0055 (12)	−0.0015 (12)	−0.0083 (12)
C82	0.0318 (16)	0.0331 (16)	0.043 (2)	−0.0120 (13)	0.0025 (14)	−0.0125 (14)
C83	0.0497 (19)	0.0384 (17)	0.038 (2)	−0.0149 (14)	−0.0004 (15)	−0.0112 (14)
C631	0.0318 (17)	0.0550 (19)	0.049 (2)	−0.0189 (15)	0.0124 (15)	−0.0130 (16)
C632	0.0432 (18)	0.0406 (17)	0.0318 (18)	−0.0149 (14)	0.0058 (14)	−0.0030 (14)

Geometric parameters (Å, º) top

N1—C2	1.292 (3)	C62—H62B	0.99
C2—N3	1.343 (3)	C63—C631	1.527 (4)
N3—C4	1.388 (3)	C63—C632	1.530 (4)
C4—C4A	1.412 (3)	C63—C64	1.531 (3)
C4A—C8A	1.378 (3)	C631—H63A	0.98
C8A—N1	1.375 (3)	C631—H63B	0.98
C4—O4	1.250 (3)	C631—H63C	0.98
C8A—N8	1.370 (3)	C632—H63D	0.98
C7—N8	1.451 (3)	C632—H63E	0.98
C2—O2	1.334 (3)	C632—H63F	0.98
O2—C21	1.447 (3)	C64—C65	1.507 (3)
C61—O61	1.213 (3)	C64—H64A	0.99
C65—O65	1.210 (3)	C64—H64B	0.99
C21—H21A	0.98	C7—H7A	0.99
C21—H21B	0.98	C7—H7B	0.99
C21—H21C	0.98	N8—C81	1.445 (3)
N3—H3	0.8798	C81—O81	1.417 (3)
C4A—C5	1.503 (3)	C81—H81A	0.99
C5—C6	1.527 (3)	C81—H81B	0.99
C5—H5A	0.99	O81—C82	1.444 (3)
C5—H5B	0.99	C82—C83	1.497 (4)
C6—C65	1.535 (3)	C82—H82A	0.99
C6—C61	1.535 (3)	C82—H82B	0.99
C6—C7	1.547 (3)	C83—H83A	0.98
C61—C62	1.505 (3)	C83—H83B	0.98
C62—C63	1.538 (3)	C83—H83C	0.98
C62—H62A	0.99

C2—N1—C8A	115.7 (2)	C63—C631—H63C	109.5
N1—C2—N3	125.1 (2)	H63A—C631—H63C	109.5
N1—C2—O2	121.8 (2)	H63B—C631—H63C	109.5
N3—C2—O2	113.1 (2)	C63—C632—H63D	109.5
C2—O2—C21	115.51 (18)	C63—C632—H63E	109.5
O2—C21—H21A	109.5	H63D—C632—H63E	109.5
O2—C21—H21B	109.5	C63—C632—H63F	109.5
H21A—C21—H21B	109.5	H63D—C632—H63F	109.5
O2—C21—H21C	109.5	H63E—C632—H63F	109.5
H21A—C21—H21C	109.5	C65—C64—C63	113.06 (19)
H21B—C21—H21C	109.5	C65—C64—H64A	109.0
C2—N3—C4	121.5 (2)	C63—C64—H64A	109.0
C2—N3—H3	119.5	C65—C64—H64B	109.0
C4—N3—H3	118.6	C63—C64—H64B	109.0
O4—C4—N3	119.4 (2)	H64A—C64—H64B	107.8
O4—C4—C4A	124.9 (2)	O65—C65—C64	122.6 (2)
N3—C4—C4A	115.7 (2)	O65—C65—C6	121.0 (2)
C8A—C4A—C4	118.0 (2)	C64—C65—C6	116.4 (2)
C8A—C4A—C5	122.1 (2)	N8—C7—C6	111.47 (18)
C4—C4A—C5	119.6 (2)	N8—C7—H7A	109.3
C4A—C5—C6	111.4 (2)	C6—C7—H7A	109.3
C4A—C5—H5A	109.3	N8—C7—H7B	109.3
C6—C5—H5A	109.3	C6—C7—H7B	109.3
C4A—C5—H5B	109.3	H7A—C7—H7B	108.0
C6—C5—H5B	109.3	C8A—N8—C81	123.4 (2)
H5A—C5—H5B	108.0	C8A—N8—C7	119.2 (2)
C5—C6—C65	112.2 (2)	C81—N8—C7	117.39 (19)
C5—C6—C61	112.37 (19)	O81—C81—N8	112.3 (2)
C65—C6—C61	109.2 (2)	O81—C81—H81A	109.1
C5—C6—C7	107.7 (2)	N8—C81—H81A	109.1
C65—C6—C7	106.27 (18)	O81—C81—H81B	109.1
C61—C6—C7	108.9 (2)	N8—C81—H81B	109.1
O61—C61—C62	122.6 (2)	H81A—C81—H81B	107.9
O61—C61—C6	121.1 (2)	C81—O81—C82	113.65 (19)
C62—C61—C6	116.2 (2)	O81—C82—C83	112.9 (2)
C61—C62—C63	111.1 (2)	O81—C82—H82A	109.0
C61—C62—H62A	109.4	C83—C82—H82A	109.0
C63—C62—H62A	109.4	O81—C82—H82B	109.0
C61—C62—H62B	109.4	C83—C82—H82B	109.0
C63—C62—H62B	109.4	H82A—C82—H82B	107.8
H62A—C62—H62B	108.0	C82—C83—H83A	109.5
C631—C63—C632	109.6 (2)	C82—C83—H83B	109.5
C631—C63—C64	109.5 (2)	H83A—C83—H83B	109.5
C632—C63—C64	109.6 (2)	C82—C83—H83C	109.5
C631—C63—C62	109.8 (2)	H83A—C83—H83C	109.5
C632—C63—C62	109.7 (2)	H83B—C83—H83C	109.5
C64—C63—C62	108.7 (2)	N8—C8A—N1	114.8 (2)
C63—C631—H63A	109.5	N8—C8A—C4A	121.2 (2)
C63—C631—H63B	109.5	N1—C8A—C4A	124.0 (2)
H63A—C631—H63B	109.5

C8A—N1—C2—O2	177.8 (2)	N8—C81—O81—C82	71.3 (3)
C8A—N1—C2—N3	0.2 (3)	C81—O81—C82—C83	82.4 (3)
N1—C2—O2—C21	5.5 (3)	C5—C6—C61—O61	5.9 (3)
N3—C2—O2—C21	−176.61 (19)	C65—C6—C61—O61	131.1 (2)
N1—C2—N3—C4	0.3 (4)	C7—C6—C61—O61	−113.3 (3)
O2—C2—N3—C4	−177.54 (19)	C5—C6—C61—C62	−172.0 (2)
C2—N3—C4—O4	−179.4 (2)	C7—C6—C61—C62	68.8 (3)
C2—N3—C4—C4A	0.0 (3)	O61—C61—C62—C63	−122.4 (3)
O4—C4—C4A—C8A	178.7 (2)	C61—C62—C63—C631	−176.4 (2)
N3—C4—C4A—C8A	−0.8 (3)	C61—C62—C63—C632	63.1 (3)
O4—C4—C4A—C5	3.4 (4)	C631—C63—C64—C65	174.9 (2)
N3—C4—C4A—C5	−176.1 (2)	C632—C63—C64—C65	−64.8 (3)
C4—C4A—C5—C6	156.1 (2)	C63—C64—C65—O65	129.8 (3)
C4A—C5—C6—C65	164.19 (19)	C5—C6—C65—O65	−11.4 (3)
C4A—C5—C6—C61	−72.3 (3)	C61—C6—C65—O65	−136.7 (2)
C4A—C5—C6—C7	47.6 (3)	C7—C6—C65—O65	106.0 (3)
C5—C6—C7—N8	−58.7 (2)	C5—C6—C65—C64	169.3 (2)
C6—C7—N8—C8A	39.4 (3)	C7—C6—C65—C64	−73.3 (3)
C7—N8—C8A—C4A	−7.4 (3)	C65—C6—C7—N8	−179.07 (19)
N8—C8A—C4A—C5	−3.4 (4)	C61—C6—C7—N8	63.4 (2)
C8A—C4A—C5—C6	−18.9 (3)	C8A—N8—C81—O81	−107.4 (2)
C6—C7—N8—C81	−142.4 (2)	C81—N8—C8A—N1	−5.5 (3)
C7—N8—C81—O81	74.4 (3)	C7—N8—C8A—N1	172.63 (19)
C6—C61—C62—C63	55.5 (3)	C81—N8—C8A—C4A	174.4 (2)
C61—C62—C63—C64	−56.8 (3)	C2—N1—C8A—N8	178.88 (19)
C62—C63—C64—C65	55.1 (3)	C2—N1—C8A—C4A	−1.1 (3)
C63—C64—C65—C6	−51.0 (3)	C4—C4A—C8A—N8	−178.56 (19)
C64—C65—C6—C61	44.1 (3)	C4—C4A—C8A—N1	1.4 (4)
C65—C6—C61—C62	−46.8 (3)	C5—C4A—C8A—N1	176.5 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···O4ⁱ	0.88	1.89	2.769 (2)	173
C7—H7B···O81ⁱⁱ	0.99	2.49	3.414 (3)	155
C7—H7A···Cg1ⁱⁱⁱ	0.99	2.62	3.535 (3)	155

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x+3, −y, −z+1; (iii) −x+2, −y, −z+1.

Experimental details

	(I)	(II)	(III)
Crystal data
Chemical formula	C₁₅H₁₉N₃O₃S	C₁₆H₂₁N₃O₄S	C₁₈H₂₅N₃O₅
M_r	321.39	351.42	363.41
Crystal system, space group	Triclinic, P1	Triclinic, P1	Triclinic, P1
Temperature (K)	120	120	120
a, b, c (Å)	7.8990 (3), 10.0386 (3), 10.0500 (3)	6.6682 (2), 11.0319 (3), 12.3449 (4)	8.9219 (5), 9.9806 (5), 11.3542 (7)
α, β, γ (°)	74.938 (2), 84.271 (2), 81.842 (2)	109.2678 (18), 99.8329 (18), 101.227 (2)	75.662 (3), 85.580 (3), 66.526 (3)
V (Å³)	760.10 (4)	813.32 (5)	898.22 (9)
Z	2	2	2
Radiation type	Mo Kα	Mo Kα	Mo Kα
µ (mm⁻¹)	0.23	0.23	0.10
Crystal size (mm)	0.42 × 0.38 × 0.20	0.15 × 0.10 × 0.03	0.15 × 0.10 × 0.10

Data collection
Diffractometer	Nonius KappaCCD diffractometer	Nonius KappaCCD diffractometer	Nonius KappaCCD diffractometer
Absorption correction	Multi-scan (SORTAV; Blessing, 1995, 1997)	Multi-scan (SORTAV; Blessing, 1995, 1997)	Multi-scan (SORTAV; Blessing, 1995, 1997)
T_min, T_max	0.921, 0.956	0.976, 0.994	0.967, 0.990
No. of measured, independent and observed [I > 2σ(I)] reflections	15364, 3462, 2923	18379, 3737, 2502	17797, 4082, 2026
R_int	0.057	0.047	0.088
(sin θ/λ)_max (Å⁻¹)	0.649	0.650	0.653

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.046, 0.125, 1.04	0.051, 0.140, 1.03	0.056, 0.164, 0.95
No. of reflections	3462	3737	4082
No. of parameters	202	238	239
No. of restraints	0	4	0
H-atom treatment	H-atom parameters constrained	H-atom parameters constrained	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	1.00, −0.42	0.28, −0.41	0.30, −0.43

Computer programs: KappaCCD Server Software (Nonius, 1997), DENZO–SMN (Otwinowski & Minor, 1997), DENZO–SMN, OSCAIL (McArdle, 2003) and SHELXS97 (Sheldrick, 1997), OSCAIL,(McArdle, 2003) and SHELXS97 (Sheldrick, 1997), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 2003), SHELXL97 and PRPKAPPA (Ferguson, 1999).

Selected geometric parameters (Å, º) for (I) top

N1—C2	1.300 (2)	C8A—N8	1.342 (2)
C2—N3	1.356 (2)	C7—N8	1.455 (2)
N3—C4	1.395 (2)	C2—S2	1.7547 (18)
C4—C4A	1.409 (2)	S2—C21	1.7983 (19)
C4A—C8A	1.391 (2)	C61—O61	1.216 (2)
C8A—N1	1.379 (2)	C65—O65	1.219 (2)
C4—O4	1.253 (2)

N1—C2—N3	125.04 (16)	N3—C2—S2	113.71 (13)
N1—C2—S2	121.25 (14)	C2—S2—C21	100.96 (9)

C4A—C5—C6—C7	51.41 (18)	C6—C61—C62—C63	58.5 (2)
C5—C6—C7—N8	−50.4 (2)	C61—C62—C63—C64	−56.58 (18)
C6—C7—N8—C8A	26.8 (3)	C62—C63—C64—C65	54.3 (2)
C7—N8—C8A—C4A	−2.5 (3)	C63—C64—C65—C6	−53.2 (2)
N8—C8A—C4A—C5	4.8 (3)	C64—C65—C6—C61	49.58 (19)
C8A—C4A—C5—C6	−30.3 (2)	C65—C6—C61—C62	−52.5 (2)

Hydrogen-bond geometry (Å, º) for (I) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···O4ⁱ	0.88	1.84	2.715 (2)	176
N8—H8···O65ⁱⁱ	0.88	2.10	2.965 (2)	166
C5—H5B···O61ⁱⁱⁱ	0.99	2.46	3.389 (2)	155
C64—H64A···Cg1^iv	0.99	2.87	3.854 (2)	173

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

Selected geometric parameters (Å, º) for (II) top

N1—C2	1.294 (3)	C8A—N8	1.362 (3)
C2—N3	1.334 (3)	C7—N8	1.456 (2)
N3—C4	1.395 (3)	C2—S2	1.756 (2)
C4—C4A	1.414 (3)	S2—C21	1.779 (3)
C4A—C8A	1.374 (3)	C61—O61	1.212 (2)
C8A—N1	1.379 (3)	C65—O65	1.206 (2)
C4—O4	1.239 (3)

N1—C2—N3	124.60 (19)	N3—C2—S2	114.25 (17)
N1—C2—S2	121.14 (19)	C2—S2—C21	99.74 (12)

C4A—C5—C6—C7	−46.1 (2)	C6—C61—C62—C63	−55.9 (2)
C5—C6—C7—N8	59.0 (2)	C61—C62—C63—C64	56.3 (2)
C6—C7—N8—C8A	−42.4 (3)	C62—C63—C64—C65	−55.6 (3)
C7—N8—C8A—C4A	12.1 (3)	C63—C64—C65—C6	52.5 (2)
N8—C8A—C4A—C5	1.0 (3)	C64—C65—C6—C61	−45.7 (2)
C8A—C4A—C5—C6	18.1 (3)	C65—C6—C61—C62	48.1 (2)
C6—C7—N8—C81A	139.6 (4)	C6—C7—N8—C81B	158.5 (4)
C7—N8—C81A—O8A	−61.9 (14)	C7—N8—C81B—O8B	−113.3 (9)

Hydrogen-bond geometry (Å, º) for (II) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···O4ⁱ	0.88	1.83	2.709 (3)	176
O8A—H8A···O61ⁱⁱ	0.84	2.00	2.767 (3)	152
O8B—H8B···O61ⁱⁱ	0.84	2.35	3.036 (4)	139
C62—H62B···O8Aⁱⁱⁱ	0.99	2.33	3.314 (4)	173

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

Selected geometric parameters (Å, º) for (III) top

N1—C2	1.292 (3)	C8A—N8	1.370 (3)
C2—N3	1.343 (3)	C7—N8	1.451 (3)
N3—C4	1.388 (3)	C2—O2	1.334 (3)
C4—C4A	1.412 (3)	O2—C21	1.447 (3)
C4A—C8A	1.378 (3)	C61—O61	1.213 (3)
C8A—N1	1.375 (3)	C65—O65	1.210 (3)
C4—O4	1.250 (3)

N1—C2—N3	125.1 (2)	N3—C2—O2	113.1 (2)
N1—C2—O2	121.8 (2)	C2—O2—C21	115.51 (18)

C4A—C5—C6—C7	47.6 (3)	C6—C61—C62—C63	55.5 (3)
C5—C6—C7—N8	−58.7 (2)	C61—C62—C63—C64	−56.8 (3)
C6—C7—N8—C8A	39.4 (3)	C62—C63—C64—C65	55.1 (3)
C7—N8—C8A—C4A	−7.4 (3)	C63—C64—C65—C6	−51.0 (3)
N8—C8A—C4A—C5	−3.4 (4)	C64—C65—C6—C61	44.1 (3)
C8A—C4A—C5—C6	−18.9 (3)	C65—C6—C61—C62	−46.8 (3)
C6—C7—N8—C81	−142.4 (2)	N8—C81—O81—C82	71.3 (3)
C7—N8—C81—O81	74.4 (3)	C81—O81—C82—C83	82.4 (3)

Hydrogen-bond geometry (Å, º) for (III) top

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···O4ⁱ	0.88	1.89	2.769 (2)	173
C7—H7B···O81ⁱⁱ	0.99	2.49	3.414 (3)	155
C7—H7A···Cg1ⁱⁱⁱ	0.99	2.62	3.535 (3)	155

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x+3, −y, −z+1; (iii) −x+2, −y, −z+1.

Footnotes

‡Postal address: Department of Electrical Engineering and Physics, University of Dundee, Dundee DD1 4HN, Scotland.

Acknowledgements

X-ray data were collected at the EPSRC X-ray Crystallographic Service, University of Southampton, England; the authors thank the staff for all their help and advice. JNL thanks NCR Self-Service, Dundee, for grants that have provided computing facilities for this work. JC and MN thank the Consejería de Educación y Ciencia (Junta de Andalucía, Spain) and the Universidad de Jaén for financial support, JQ thanks COLCIENCIAS and the Universidad de Valle for financial support, and SC thanks COLCIENCIAS and the Universidad de Nariño for financial support.

References

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ISSN: 2053-2296

Volume 60| Part 6| June 2004| Pages o438-o443

doi:10.1107/S0108270104009539

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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Three hexa­hydro­pyrido­pyrimidine-spiro-cyclo­hexane­triones: supra­molecular structures generated by O—H⋯O, N—H⋯O, C—H⋯O and C—H⋯π hydrogen bonds, and π–π stacking interactions

Comment

Experimental

Compound (I)

Crystal data

Data collection

Refinement

Compound (II)

Crystal data

Data collection

Refinement

Compound (III)

Crystal data

Data collection

Refinement

Supporting information

Footnotes

Acknowledgements

References

organic compounds

Three hexahydropyridopyrimidine-spiro-cyclohexanetriones: supramolecular structures generated by O—H⋯O, N—H⋯O, C—H⋯O and C—H⋯π hydrogen bonds, and π–π stacking interactions