4-Oxo-N-phenyl-4H-chromene-2-carboxamide and of a new polymorph of 7-meth­oxy-4-oxo-N-p-tolyl-4H-chromene-2-carboxamide and its hemihydrate

4-Oxo-N-phenyl-4H-chromene-2-carboxamide, C₁₆H₁₁NO₃, crystallizes in the space group P2₁/n and its derivative 7-me­th­oxy-4-oxo-N-p-tolyl-4H-chromene-2-carboxamide, C₁₈H₁₅NO₄, forms two polymorphs which crystallize in the space groups P2₁/c and P. The structures have an anti-rotamer conformation about the C-N bond; however, the amide O atom can be either trans- or cis-related to the O atom of the pyran ring. The latter compound also crystallizes as a hemihydrate, C₁₈H₁₅NO₄·0.5H₂O, in the space group C2/c. This compound has a similar structure to that of the unsolvated compound.

S1. Introduction

Chromones are a group of natural and synthetic oxygen heterocyclic compounds having a high degree of chemical diversity that is frequently linked to a broad array of biological activities. In particular, chromone carboxamides have been used by our group as a basic structure for the discovery and development of new chemical entities (NCEs) with application in neurodegenerative illnesses (Gaspar, Reis et al., 2011) and cancer (Gaspar et al. 2012). In fact, decoration on the chromone carboxamide core have led to promising outcomes either as mono­amine oxidase B (MAO-B) inhibitors or ligands for the adenosine receptors, (Gaspar, Reis et al., 2011; Gaspar et al., 2012).

Accordingly 7-meth­oxy-4-oxo-N-phenyl-4H-chromene-2-carboxamide, (1), 4-oxo-N-phenyl-4H-chromene-2-carboxamide, (2), and 7-meth­oxy-4-oxo-N-p-tolyl-4H-chromene-2-carboxamide, (3), have been synthesized and characterised by NMR and MS–EI (Gaspar et al., 2013). The crystal and molecular structure of (2) has been reported by (Reis et al., 2013). The unambiguous characterization of those compounds with respect to their molecular structures and conformations as well as their supra­molecular structures, permits the elucidation of the degree of solvation and the identification of polymorphism.

This type of information represents a valuable tool for moving on the drug discovery project based on the chromone carboxamide scaffold as it contributes to a deep exploration of structure–activity relationships and leads to the unveiling of satisfactory molecular docking models.

This work reports structures of chromones (1) and (3). Chromone (1) (Fig. 1) consists of a chromone ring linked at the 2-position to a phenyl ring via an amide group. Fig. 1 shows compound (3) which is an analogue of (1), built with a meth­oxy substituent at position 7 of the chromone ring and a methyl group at the para-position of the exocyclic phenyl ring. Compound (3) was found to crystallize in 3 different forms, a hemihydrate (3a) and polymorphic forms (3b) and (3c). Form (3b) has been characterized previously (Gomes et al., 2013) so this structure will be used for comparative discussion purposes. It crystallized in the space group P21/c, while polymorph (3c) crystallized in the space group P1. Compound (3a) is a hemihydrate of (3b) and crystallizes in the space group C2/c. Furthermore, (3a) was found to be similar to 7-meth­oxy-4-oxo-N-phenyl-4H-chromene-2-carboxamide, (2a) (Reis et al., 2013). The x and z atomic coordinates of the latter compound are similar to those of (3a); however, the y coordinates are different.

S2. Experimental

S2.1. Synthesis and crystallization

Chromones (1), (2), and (3) were obtained following synthetic strategies described elsewhere (Gaspar, Silva et al., 2011; Gaspar et al., 2013; Reis et al., 2013). In all the reactions, the crude products were purified by column chromatography and then recrystallized.The spectroscopic data (NMR and MS–EI) are in accordance with the literature (Gaspar, Silva et al., 2011; Gaspar et al., 2013; Reis et al., 2013). Crystals suitable for X-ray analysis were recrystallised from acetone [for (3a)] or methanol [for (3c)].

S2.2. Refinement

For (1), H atoms were treated as riding atoms, with aromatic C—H = 0.93 Å and U_iso = 1.2U_eq(C). For (3a) and (3c), H atoms were treated as riding atoms, with aromatic C—H = 0.95 Å and methyl C—H = 0.98Å, with U_iso = 1.5U_eq(C). The H atom attached to N2 was located on a difference map and refined and its position, and those of the methyl H atoms checked on a final difference Fourier map. In (3a), the position of the H atom on the water molecule, which sits on a twofold axis, was located on a difference Fourier map and refined and its position checked on a final difference Fourier map.

The higher R factor and goodness-of-fit for (3a) are a result of the quality of the crystals of this compounds, which are very thin plates resulting in a data set with a large number of weak reflections; the number of reflections classed as observed is only 81%, despite a data completeness of 0.983 at a θ of 25°. The presence of a large number of weak reflections, accounts for the high K values in the analysis of variance.

S3. Results and Discussion

S3.1. Molecular conformation

The displacement ellipsoid diagrams of (1), (3b) and (3c) with the atom-numbering schemes are shown in Figs. 2–4. Fig. 5 shows schematically the conformations found around the C—N rotamer for those compounds. All compounds have an anti-rotamer conformation, as expected since this conformation lowers the steric hindrance between the two aromatic rings as compared to the syn-rotamer conformation; A1 refers to the –anti--rotamer with cis related-O atoms and A2 refers to the –anti-rotamer with trans-related O atoms.

Structural analysis reveals that (1) adopts an A1 conformation where atom O1 of the pyran ring is cis-related with the O atom of the carbonyl group. This conformation contrasts with that adopted by the majority of similar chromones that have been previously characterized (Gomes et al., 2013) and with those of the related compounds (2a) and (3b), as can be seen in Fig. 1. Nevertheless this is the same conformation found for compound (3c) and for N-(4-bromo­phenyl)-4-oxo-4H-chromene-2-carboxamide (Gomes et al., 2013). This conformation precludes the formation of an intra­molecular N—H···O(pyran) hydrogen bond that can be found in chromones where the amide O atom is trans-related to the pyran O atom, as happens in (2a) and (3a). However, a weak intra­molecular bond does exist between C(ortho)—H of the benzyl ring and the carboxamide O atom, making an S(6) ring (Bernstein et al., 1995).

In (2a), (3a) and (3b), the amide O atom is trans-related to atom O1 of the pyran ring, see A2 of Fig. 5, allowing for the possible establishment of an intra­molecular hydrogen bond, N—H···O(pyran) forming a, S(5) ring (Gomes et al., 2013) and a C(ortho)—H···O intra­molecular hydrogen bond making an S(6) ring (Bernstein et al., 1995). In the hydrated compounds, atom N2 also acts as a donor to the water O atom, linking the crystallization solvent to the chromone.

Relevant data for the discussion of molecular structures and conformations of the compounds is presented in Table 5; θ₁ refers to the dihedral angles between the mean planes of the chromone and phenyl rings, θ₂ to the dihedral angle between the best plane of the chromone and the plane defined by atoms O2/C21/N2 of the amide moiety, whereas θ₃ refers to the dihedral angle between this plane and the best plane of the benzene ring. Since the aromatic rings are practically planar, the dihedral θ₁ qu­anti­fies the degree of bend and/or twist between the aromatic rings.

The dihedral angle of 6.57 (7)° for (1) is mainly due to the bending between the two aromatic rings since the values of θ₂ and θ₃ are similar.

In the case of the 7-meth­oxy compounds, the dihedral angles between the chromone and exocyclic benzene rings is of the same order for all compounds except (3b) which has a value almost double the others. The value of θ₃ is very much greater than θ₂ for this compound. This is the reverse of what is found for the other 7-meth­oxy compounds in which θ₂ is greater than θ₃.

Comparing the θ₂ and θ₃ values for those compounds and the difference between θ₂ and θ₃ is very close to the value of θ₁ which suggests that the twist of the chromone and exocyclic phenyl rings with respect to the O2—C21—N2 plane is the main contributor to the dihedral angle between the rings. In the case of (3b), the main contribution is from the twist between the benzene ring and the O2—C21—N2 plane which is the main contributor in the remaining compounds it is the twist between the chromone ring and the O2—C21—N2 plane.

Polymorphism assumes a special relevance in these chromone carboxamides as both conformational [(3b)/(3c) pair] and pseudo-polymorphism [(2a)/(3a) pair] is observed. The different polymorphs were obtained with different solvents of crystallization showing that the solvent plays an important role on the crystallization processes. The hemihydrated compound (3a) was obtained when chloro­form and acetone solutions were used for crystallization while the water free compounds (3b) and (3c) were obtained in ethyl acetate/n-hexane and methanol, respectively. Attempts to isolate the possible nonhydrated polymorphs of (2) were unsuccessful. Several crystallization solvents were tried (acetone, methanol, di­chloro­ethane, chloro­form, di­chloro­methane and ethyl acetate), but, in all cases, the hemihydrated structure (2a) was obtained.

The identification of polymorphism assumes a special relevance in these compounds since they will be used in pharmacological assays. Purification of those chromones by crystallization gives different conformers. As a result extra care in the selection of the purification technique is of utmost relevance. Also the structural results show that, in (3) both hydrated and nonhydrated forms of the A2 conformation are stable and so previous identification of which form is present in the sample is mandatory in order to perform accurate dose–activity studies.

S3.2. Supra­molecular structure

The geometric parameters for the inter­molecular hydrogen-bond inter­actions are given in Tables 2, 3 and 4.

In (1), the molecules are linked across the centre of symmetry at (1/2, 1, 1/2), forming head-to-tail centrosymmetric dimers which are linked by the N2—H2···O4ⁱ [symmetry code: (i) -x+1, -y+2, -z+1), which forms an R₂²(14) ring (Bernstein et al., 1995). This is supplemented by weak C3—H3···O4ⁱ and C21—H212···O4ⁱ hydrogen bonds which form R₂²(8) and R₂²(14) rings (Bernstein et al., 1995). respectively (Fig. 6). The N2–H2···O2ⁱⁱ [symmetry code: (ii) x, y+1, z] hydrogen bond links the molecules into C(4) chains (Bernstein et al., 1995) which run parallel to the b axis. This is a weaker N—H···O inter­action since the angle at H2 is 124 (17)° (Fig. 7). The dimers are joined by centrosymmetrically related C7—H7···O2ⁱⁱⁱ [symmetry code: (iii) -x+2, -y, -z+1] inter­actions across the centre of symmetry at (1, 0, 1/2), forming R₂²(16) rings (Bernstein et al., 1995) (Fig. 8).

In (3a), the N2—H2···O3 (within the selected asymmetric unit) and the N—H group at (-x+1, y, -z+1/2) act as hydrogen-bond donors to the water molecule at (1/2, y, 1/4) which in turn acts as hydrogen donor via O3—H3···O4^iv [symmetry code: (iv) -x+1, y-1, -z+1/2] and to O4 at (x, y-1, z) (Fig. 9). This is supplemented by the weak C215—H215···O2^v [symmetry code: (v) x, y-1, z] inter­action. This forms a ribbon structure which runs parallel to the b axis in which the molecules are related by unit translations along the b axis and by the action of the twofold axis on which the water molecule sits. Adjacent chains are linked by a weak C71—H(methyl) inter­action to atom O2 at (-x+1/2, y+1/2, -z+1/2) forming a stacked sheet of molecules which lies in the ab plane (Fig. 10). There are two such anti­parallel sheets in the unit cell. There are two π–π contacts in which the centre-of-gravity separations are less that 4.0 Å. These involve the pyran rings at (x, y, z) and (-x+1, y, z-1/2) in which the centre-of-gravity to centre-of-gravity distance is 3.765 (4) Å and the chromone phenyl ring at (x, y, z) and the p-tolyl phenyl ring at (-x+1/2, y+1, -z+1/2), in which this distance is 3.594 (4) Å.

Dimers similar to those in (1) are found in the structure in (3c). Here the molecules are linked across the centre of symmetry at (1,1/2,1/2) forming head-to-tail centrosymmetric dimers which are linked by the N2—H2···O4^vi hydrogen bond [symmetry code: (vi) -x+2, -y+1, -z+1], which forms an R₂²(14) ring (Bernstein et al., 1995). This is supplemented by weak C3—H3···O4^vi and C212—H212···O4^vi hydrogen bonds which form R₂²(8) and R₂²(14) rings (Bernstein et al., 1995), respectively (Fig. 11). These dimers are also found in the structure of N-(4-bromo­phenyl)-4-oxo-4H-chromene-2-carboxamide (Gomes et al., 2013). The dimers are also linked by the C216—H216···O2^vii [symmetry code: (vii) -x, -y, -z+1] weak hydrogen bond which lie across the centre of symmetry at (0, 0, 1/2) (Fig. 12). The dimers are also linked to form chains by the C6—H6···O7^viii [symmetry code: (viii) -x+2, -y, -z] weak hydrogen bond which lie across the centre of symmetry at (1, 0, 0). These inter­actions combine to link the molecules into a two-dimensional sheet (Fig. 13).

In (3b), the molecules are linked into chains by a hydrogen bond between the amino H atom and the 4-oxo O atom atom reinforced by weak C—H···O inter­actions. C—H···π and π–π stacking inter­actions are also present (Gomes et al., 2013)

Related literature

For related literature, see: Bernstein et al. (1995); Gaspar et al. (2012, 2013); Gaspar, Reis, Fonseca, Milhazes, Vina, Uriarte & Borges (2011); Gaspar, Silva, Yanez, Vina, Orallo, Ortuso, Uriarte, Alcaro & Borges (2011); Gomes et al. (2013); Reis et al. (2013).

Computing details

Data collection: SMART (Bruker, 1997) for (1); CrystalClear-SM Expert (Rigaku, 2011) for (3a), (3c). Cell refinement: SMART (Bruker, 1997) for (1); CrystalClear-SM Expert (Rigaku, 2011) for (3a), (3c). Data reduction: SAINT (Bruker, 1997) for (1); CrystalClear-SM Expert (Rigaku, 2011) for (3a), (3c). For all compounds, program(s) used to solve structure: SHELXS97 (Sheldrick, 2008). Program(s) used to refine structure: OSCAIL (McArdle et al., 2004) and SHELXL97 (Sheldrick, 2008) for (1); OSCAIL (McArdle et al., 2004), SHELXLE (Hübschle et al., 2011) and SHELXL97 (Sheldrick, 2008) for (3a), (3c). For all compounds, molecular graphics: Mercury (Macrae et al., 2006). Software used to prepare material for publication: OSCAIL (McArdle et al., 2004) and SHELXS97 (Sheldrick, 2008) for (1); OSCAIL (McArdle et al., 2004) and SHELXL97 (Sheldrick, 2008) for (3a), (3c).

Figures

	Fig. 1. The relationships of the compounds discussed in this paper, showing the conformations of the C—N rotamers formed. Note that the conformations of carboxamides (1) and (3c) are the same, but different from those of (2a), (3a) and (3b) which are the same.
	Fig. 2. A view of the asymmetric unit of (1), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 70% probability level.
	Fig. 3. A view of the asymmetric unit of hemihydrate (3a), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 70% probability level. The dashed bonds show the intramolecular hydrogen bonds and the hydrogen bond between atom N2 and the water molecule.
	Fig. 4. A view of the asymmetric unit of (3c), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 70% probability level.
	Fig. 5. Possible intramolecular hydrogen bonding for compounds discussed in this paper and related compounds.
	Fig. 6. The centrosymmetric dimer formed by the molecules of (1). Hydrogen bonds are indicated by dashed lines. H atoms not involved in hydrogen bonding have been omitted for clarity.
	Fig. 7. The N2—H2···O2 C(4) chain formed by the molecules of (1). This chain runs parallel to the b axis. Hydrogen bonds are indicated by dashed lines. H atoms not involved in hydrogen bonding have been omitted for clarity.
	Fig. 8. Part of the structure of (1), showing the chain of linked centrosymmetric dimers formed by the action of the weak C7—H7···O2 centrosymmetrically related hydrogen bonds. Hydrogen bonds are indicated by dashed lines. H atoms not involved in hydrogen bonding have been omitted for clarity.
	Fig. 9. Part of the crystal structure of hemihydrate (3a), showing the hydrogen bonding around the water molecule viewed down the a axis. Hydrogen bonds are indicated b dashed lines. H atoms not involved in hydrogen bonding have been omitted for clarity.
	Fig. 10. Part of the crystal structure of hemihydrate (3a), showing the chain formed by molecules linked by the water molecules running parallel to the b axis. Adjacent chains are linked by a weak C—H(methyl)···O hydrogen bond. Hydrogen bonds are indicated by dashed lines. H atoms not involved in hydrogen bonding have been omitted for clarity.
	Fig. 11. The centrosymmetric dimer formed by the molecules of (3c). Hydrogen bonds are indicated by dashed lines. H atoms not involved in hydrogen bonding have been omitted for clarity.
	Fig. 12. Part of the structure of (3c), showing the chain of linked dimers. Hydrogen bonds are indicated by dashed lines. H atoms not involved in hydrogen bonding have been omitted for clarity.
	Fig. 13. Part of the structure of (3c), showing the sheet formed by linked dimers. Hydrogen bonds are indicated by dashed lines. H atoms not involved in hydrogen bonding have been omitted for clarity.

(1) 4-Oxo-N-phenyl-4H-chromene-2-carboxamide

Crystal data

C16H11NO3	F(000) = 552
Mr = 265.26	Dx = 1.450 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 7463 reflections
a = 8.6591 (12) Å	θ = 2.4–28.0°
b = 4.9980 (7) Å	µ = 0.10 mm^−1
c = 28.346 (4) Å	T = 293 K
β = 98.042 (3)°	Plate, colourless
V = 1214.7 (3) Å^3	0.45 × 0.42 × 0.10 mm
Z = 4

Data collection

Bruker SMART 1000 CCD diffractometer	2888 independent reflections
Radiation source: fine-focus sealed tube	1826 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.029
profile data from ω–scans	θmax = 28.0°, θmin = 2.4°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −11→11
Tmin = 0.956, Tmax = 0.990	k = −6→6
7463 measured reflections	l = −37→19

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.125	H atoms treated by a mixture of independent and constrained refinement
S = 1.02	w = 1/[σ^2(Fo^2) + (0.0551P)^2 + 0.2464P] where P = (Fo^2 + 2Fc^2)/3
2888 reflections	(Δ/σ)max = 0.002
185 parameters	Δρmax = 0.24 e Å^−3
0 restraints	Δρmin = −0.19 e Å^−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
O1	0.82867 (13)	0.3480 (2)	0.49648 (4)	0.0361 (3)
O2	0.75473 (16)	0.2649 (2)	0.40550 (4)	0.0502 (4)
O4	0.58673 (14)	0.8742 (2)	0.56868 (4)	0.0461 (3)
N2	0.63731 (17)	0.6713 (3)	0.39309 (5)	0.0396 (4)
H2	0.611 (2)	0.811 (4)	0.4066 (7)	0.055 (6)*
C2	0.72650 (17)	0.5261 (3)	0.47339 (5)	0.0318 (4)
C3	0.64846 (19)	0.7060 (3)	0.49584 (6)	0.0359 (4)
H3	0.5832	0.8272	0.4779	0.043*
C4	0.66284 (18)	0.7170 (3)	0.54743 (6)	0.0341 (4)
C4A	0.77247 (17)	0.5227 (3)	0.57203 (6)	0.0322 (4)
C5	0.8003 (2)	0.5045 (4)	0.62179 (6)	0.0417 (4)
H5	0.7476	0.6176	0.6402	0.050*
C6	0.9046 (2)	0.3209 (4)	0.64363 (6)	0.0472 (5)
H6	0.9221	0.3094	0.6767	0.057*
C7	0.9842 (2)	0.1522 (4)	0.61632 (6)	0.0422 (4)
H7	1.0556	0.0299	0.6314	0.051*
C8	0.95899 (18)	0.1634 (3)	0.56746 (6)	0.0369 (4)
H8	1.0122	0.0497	0.5493	0.044*
C8A	0.85219 (17)	0.3484 (3)	0.54566 (5)	0.0314 (4)
C21	0.70918 (17)	0.4752 (3)	0.42037 (6)	0.0340 (4)
C211	0.59303 (19)	0.6705 (3)	0.34289 (6)	0.0344 (4)
C212	0.4823 (2)	0.8557 (4)	0.32447 (6)	0.0471 (5)
H212	0.4410	0.9743	0.3447	0.056*
C213	0.4326 (2)	0.8646 (4)	0.27588 (7)	0.0548 (5)
H213	0.3576	0.9889	0.2636	0.066*
C214	0.4934 (2)	0.6910 (4)	0.24557 (7)	0.0520 (5)
H214	0.4591	0.6963	0.2130	0.062*
C215	0.6047 (2)	0.5105 (4)	0.26384 (6)	0.0542 (5)
H215	0.6468	0.3944	0.2434	0.065*
C216	0.6561 (2)	0.4978 (4)	0.31244 (6)	0.0479 (5)
H216	0.7320	0.3745	0.3244	0.057*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0405 (6)	0.0361 (6)	0.0310 (6)	0.0110 (5)	0.0029 (5)	0.0007 (5)
O2	0.0680 (8)	0.0432 (7)	0.0383 (7)	0.0215 (6)	0.0031 (6)	−0.0039 (6)
O4	0.0517 (7)	0.0467 (7)	0.0399 (7)	0.0175 (6)	0.0068 (6)	−0.0053 (6)
N2	0.0541 (9)	0.0323 (8)	0.0310 (8)	0.0100 (7)	0.0012 (6)	−0.0033 (6)
C2	0.0326 (8)	0.0284 (8)	0.0335 (9)	0.0015 (6)	0.0016 (7)	0.0015 (7)
C3	0.0387 (9)	0.0332 (9)	0.0347 (9)	0.0084 (7)	0.0008 (7)	0.0009 (7)
C4	0.0342 (8)	0.0307 (8)	0.0371 (9)	0.0027 (7)	0.0034 (7)	−0.0028 (7)
C4A	0.0321 (8)	0.0299 (8)	0.0342 (8)	−0.0001 (6)	0.0027 (6)	−0.0014 (7)
C5	0.0484 (10)	0.0415 (10)	0.0353 (10)	0.0076 (8)	0.0058 (8)	−0.0032 (8)
C6	0.0587 (11)	0.0497 (11)	0.0319 (9)	0.0088 (9)	0.0015 (8)	0.0044 (8)
C7	0.0423 (9)	0.0410 (10)	0.0415 (10)	0.0088 (8)	−0.0008 (8)	0.0080 (8)
C8	0.0356 (9)	0.0351 (9)	0.0401 (9)	0.0059 (7)	0.0055 (7)	0.0024 (7)
C8A	0.0324 (8)	0.0303 (8)	0.0309 (8)	−0.0015 (6)	0.0025 (6)	0.0012 (7)
C21	0.0348 (8)	0.0315 (9)	0.0350 (9)	0.0028 (7)	0.0027 (7)	−0.0021 (7)
C211	0.0396 (9)	0.0328 (9)	0.0299 (8)	−0.0022 (7)	0.0016 (7)	0.0008 (7)
C212	0.0545 (11)	0.0466 (11)	0.0400 (10)	0.0141 (9)	0.0066 (8)	0.0012 (8)
C213	0.0577 (12)	0.0582 (13)	0.0450 (11)	0.0127 (10)	−0.0053 (9)	0.0099 (10)
C214	0.0638 (12)	0.0558 (12)	0.0331 (10)	−0.0046 (10)	−0.0043 (9)	0.0012 (9)
C215	0.0721 (13)	0.0539 (12)	0.0357 (10)	0.0073 (10)	0.0046 (9)	−0.0068 (9)
C216	0.0568 (11)	0.0451 (11)	0.0400 (11)	0.0111 (9)	0.0007 (9)	−0.0032 (8)

Geometric parameters (Å, º)

O1—C2	1.3571 (17)	C6—H6	0.9300
O1—C8A	1.3805 (18)	C7—C8	1.373 (2)
O2—C21	1.2182 (19)	C7—H7	0.9300
O4—C4	1.2353 (18)	C8—C8A	1.390 (2)
N2—C21	1.346 (2)	C8—H8	0.9300
N2—C211	1.421 (2)	C211—C212	1.382 (2)
N2—H2	0.84 (2)	C211—C216	1.386 (2)
C2—C3	1.338 (2)	C212—C213	1.385 (3)
C2—C21	1.511 (2)	C212—H212	0.9300
C3—C4	1.451 (2)	C213—C214	1.377 (3)
C3—H3	0.9300	C213—H213	0.9300
C4—C4A	1.464 (2)	C214—C215	1.368 (3)
C4A—C8A	1.392 (2)	C214—H214	0.9300
C4A—C5	1.400 (2)	C215—C216	1.389 (2)
C5—C6	1.373 (2)	C215—H215	0.9300
C5—H5	0.9300	C216—H216	0.9300
C6—C7	1.391 (2)
C2—O1—C8A	118.69 (12)	C7—C8—H8	120.7
C21—N2—C211	127.70 (15)	C8A—C8—H8	120.7
C21—N2—H2	118.2 (14)	O1—C8A—C8	116.28 (14)
C211—N2—H2	114.0 (14)	O1—C8A—C4A	121.94 (13)
C3—C2—O1	123.37 (14)	C8—C8A—C4A	121.78 (15)
C3—C2—C21	126.87 (14)	O2—C21—N2	125.14 (16)
O1—C2—C21	109.66 (13)	O2—C21—C2	119.84 (14)
C2—C3—C4	121.80 (14)	N2—C21—C2	114.98 (14)
C2—C3—H3	119.1	C212—C211—C216	119.68 (15)
C4—C3—H3	119.1	C212—C211—N2	116.89 (15)
O4—C4—C3	122.63 (14)	C216—C211—N2	123.43 (15)
O4—C4—C4A	122.95 (15)	C211—C212—C213	119.99 (17)
C3—C4—C4A	114.41 (13)	C211—C212—H212	120.0
C8A—C4A—C5	118.15 (14)	C213—C212—H212	120.0
C8A—C4A—C4	119.75 (14)	C214—C213—C212	120.51 (18)
C5—C4A—C4	122.10 (14)	C214—C213—H213	119.7
C6—C5—C4A	120.48 (16)	C212—C213—H213	119.7
C6—C5—H5	119.8	C215—C214—C213	119.34 (17)
C4A—C5—H5	119.8	C215—C214—H214	120.3
C5—C6—C7	120.00 (16)	C213—C214—H214	120.3
C5—C6—H6	120.0	C214—C215—C216	121.11 (18)
C7—C6—H6	120.0	C214—C215—H215	119.4
C8—C7—C6	121.06 (16)	C216—C215—H215	119.4
C8—C7—H7	119.5	C211—C216—C215	119.35 (17)
C6—C7—H7	119.5	C211—C216—H216	120.3
C7—C8—C8A	118.51 (15)	C215—C216—H216	120.3
C8A—O1—C2—C3	1.0 (2)	C4—C4A—C8A—O1	−1.5 (2)
C8A—O1—C2—C21	−175.36 (13)	C5—C4A—C8A—C8	−1.2 (2)
O1—C2—C3—C4	−2.5 (2)	C4—C4A—C8A—C8	179.07 (15)
C21—C2—C3—C4	173.17 (15)	C211—N2—C21—O2	3.5 (3)
C2—C3—C4—O4	−176.89 (16)	C211—N2—C21—C2	−174.27 (15)
C2—C3—C4—C4A	1.9 (2)	C3—C2—C21—O2	−160.73 (17)
O4—C4—C4A—C8A	178.85 (16)	O1—C2—C21—O2	15.5 (2)
C3—C4—C4A—C8A	0.1 (2)	C3—C2—C21—N2	17.1 (2)
O4—C4—C4A—C5	−0.9 (3)	O1—C2—C21—N2	−166.68 (13)
C3—C4—C4A—C5	−179.70 (16)	C21—N2—C211—C212	161.49 (17)
C8A—C4A—C5—C6	0.6 (3)	C21—N2—C211—C216	−19.2 (3)
C4—C4A—C5—C6	−179.61 (16)	C216—C211—C212—C213	1.2 (3)
C4A—C5—C6—C7	0.3 (3)	N2—C211—C212—C213	−179.44 (17)
C5—C6—C7—C8	−0.8 (3)	C211—C212—C213—C214	−0.4 (3)
C6—C7—C8—C8A	0.2 (3)	C212—C213—C214—C215	−0.6 (3)
C2—O1—C8A—C8	−179.48 (14)	C213—C214—C215—C216	0.7 (3)
C2—O1—C8A—C4A	1.1 (2)	C212—C211—C216—C215	−1.1 (3)
C7—C8—C8A—O1	−178.71 (15)	N2—C211—C216—C215	179.58 (17)
C7—C8—C8A—C4A	0.7 (2)	C214—C215—C216—C211	0.2 (3)
C5—C4A—C8A—O1	178.25 (15)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O2^i	0.84 (2)	2.59 (2)	3.140 (2)	124 (17)
N2—H2···O4^ii	0.84 (2)	2.50 (2)	3.2690 (19)	153 (18)
C3—H3···O4^ii	0.93	2.36	3.294 (2)	179
C212—H212···O4^ii	0.93	2.61	3.444 (2)	149
C7—H7···O2^iii	0.93	2.54	3.199 (2)	128

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

(3a) 7-Methoxy-4-oxo-N-p-tolyl-4H-chromene-2-carboxamide hemihydrate

Crystal data

C18H15NO4·0.5H2O	F(000) = 1336
Mr = 318.32	Dx = 1.351 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71075 Å
Hall symbol: -C 2yc	Cell parameters from 3415 reflections
a = 12.989 (12) Å	θ = 2.8–27.4°
b = 8.301 (7) Å	µ = 0.10 mm^−1
c = 29.11 (2) Å	T = 100 K
β = 94.29 (2)°	Plate, colourless
V = 3130 (4) Å^3	0.23 × 0.12 × 0.02 mm
Z = 8

Data collection

Rigaku Saturn724+ (2x2 bin mode) diffractometer	2716 independent reflections
Radiation source: Sealed Tube	2401 reflections with I > 2σ(I)
Mirrors monochromator	Rint = 0.071
Detector resolution: 28.5714 pixels mm^-1	θmax = 25.0°, θmin = 2.9°
profile data from ω–scans	h = −15→10
Absorption correction: multi-scan (CrystalClear-SM Expert; Rigaku, 2011)	k = −9→9
Tmin = 0.978, Tmax = 0.998	l = −34→34
11349 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.096	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.208	H atoms treated by a mixture of independent and constrained refinement
S = 1.25	w = 1/[σ^2(Fo^2) + (0.0516P)^2 + 10.5932P] where P = (Fo^2 + 2Fc^2)/3
2716 reflections	(Δ/σ)max < 0.001
223 parameters	Δρmax = 0.24 e Å^−3
0 restraints	Δρmin = −0.32 e Å^−3

Special details

Experimental. The data was restricted to 25.02 degrees for the refinement.

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
O1	0.36292 (19)	0.2421 (3)	0.23558 (8)	0.0288 (7)
O2	0.3694 (2)	0.3765 (3)	0.35043 (9)	0.0342 (7)
O7	0.3261 (2)	0.1180 (3)	0.07462 (9)	0.0326 (7)
O3	0.5000	−0.0576 (5)	0.2500	0.0295 (9)
H3A	0.552 (5)	−0.119 (8)	0.263 (2)	0.11 (2)*
O4	0.3617 (2)	0.7280 (3)	0.20722 (10)	0.0356 (7)
N2	0.3991 (2)	0.1256 (4)	0.32042 (11)	0.0267 (7)
H2	0.413 (4)	0.068 (6)	0.2936 (17)	0.063 (16)*
C2	0.3689 (3)	0.3544 (5)	0.26967 (12)	0.0264 (8)
C3	0.3671 (3)	0.5150 (5)	0.26206 (13)	0.0295 (9)
H3	0.3694	0.5869	0.2875	0.035*
C4	0.3617 (3)	0.5792 (5)	0.21554 (14)	0.0299 (9)
C4A	0.3558 (3)	0.4579 (5)	0.17918 (14)	0.0298 (9)
C5	0.3490 (3)	0.5015 (5)	0.13225 (13)	0.0311 (9)
H5	0.3502	0.6119	0.1237	0.037*
C6	0.3405 (3)	0.3837 (5)	0.09886 (14)	0.0334 (9)
H6	0.3368	0.4133	0.0673	0.040*
C7	0.3373 (3)	0.2201 (5)	0.11111 (13)	0.0293 (9)
C8	0.3456 (3)	0.1730 (5)	0.15668 (13)	0.0306 (9)
H8	0.3452	0.0623	0.1650	0.037*
C8A	0.3545 (3)	0.2934 (5)	0.19010 (12)	0.0265 (9)
C21	0.3793 (3)	0.2868 (5)	0.31771 (12)	0.0255 (8)
C71	0.3211 (3)	−0.0530 (5)	0.08438 (14)	0.0359 (10)
H71A	0.3100	−0.1128	0.0554	0.054*
H71B	0.2639	−0.0740	0.1037	0.054*
H71C	0.3861	−0.0878	0.1007	0.054*
C211	0.4070 (3)	0.0288 (5)	0.36091 (12)	0.0265 (8)
C212	0.4098 (3)	0.0889 (5)	0.40580 (13)	0.0317 (9)
H212	0.4075	0.2017	0.4111	0.038*
C213	0.4158 (3)	−0.0172 (5)	0.44256 (14)	0.0321 (9)
H213	0.4175	0.0246	0.4730	0.039*
C214	0.4195 (3)	−0.1847 (5)	0.43626 (13)	0.0330 (9)
C215	0.4184 (3)	−0.2425 (5)	0.39132 (13)	0.0318 (9)
H215	0.4219	−0.3553	0.3861	0.038*
C216	0.4123 (3)	−0.1375 (5)	0.35404 (13)	0.0298 (9)
H216	0.4116	−0.1792	0.3236	0.036*
C217	0.4251 (4)	−0.2995 (6)	0.47647 (14)	0.0427 (11)
H21A	0.3625	−0.3657	0.4752	0.064*
H21B	0.4307	−0.2382	0.5053	0.064*
H21C	0.4856	−0.3693	0.4751	0.064*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0230 (15)	0.0271 (15)	0.0361 (15)	0.0016 (11)	0.0017 (11)	0.0012 (11)
O2	0.0365 (17)	0.0313 (16)	0.0353 (15)	0.0012 (13)	0.0068 (12)	−0.0044 (13)
O7	0.0316 (16)	0.0341 (16)	0.0321 (14)	0.0019 (13)	0.0021 (12)	−0.0004 (12)
O3	0.027 (2)	0.029 (2)	0.033 (2)	0.000	0.0050 (17)	0.000
O4	0.0310 (17)	0.0239 (15)	0.0511 (18)	−0.0010 (12)	−0.0017 (13)	0.0018 (13)
N2	0.0221 (18)	0.0305 (18)	0.0276 (17)	0.0009 (14)	0.0025 (13)	−0.0005 (14)
C2	0.0155 (19)	0.031 (2)	0.033 (2)	−0.0029 (16)	0.0021 (14)	−0.0112 (17)
C3	0.024 (2)	0.028 (2)	0.037 (2)	0.0032 (17)	0.0012 (16)	−0.0040 (17)
C4	0.0130 (19)	0.031 (2)	0.045 (2)	−0.0013 (16)	−0.0010 (16)	−0.0027 (18)
C4A	0.018 (2)	0.028 (2)	0.043 (2)	0.0006 (16)	0.0018 (16)	−0.0023 (17)
C5	0.021 (2)	0.034 (2)	0.038 (2)	−0.0016 (17)	0.0026 (16)	0.0068 (18)
C6	0.023 (2)	0.043 (2)	0.035 (2)	0.0028 (18)	0.0031 (16)	0.0047 (18)
C7	0.0176 (19)	0.038 (2)	0.033 (2)	0.0035 (17)	0.0015 (15)	0.0013 (17)
C8	0.0155 (19)	0.031 (2)	0.045 (2)	0.0008 (16)	0.0029 (16)	−0.0017 (18)
C8A	0.0154 (19)	0.032 (2)	0.032 (2)	0.0039 (16)	0.0012 (15)	0.0035 (17)
C21	0.0150 (18)	0.029 (2)	0.032 (2)	−0.0022 (16)	−0.0006 (14)	−0.0021 (17)
C71	0.032 (2)	0.041 (3)	0.035 (2)	−0.0028 (19)	0.0070 (17)	−0.0085 (18)
C211	0.0166 (19)	0.033 (2)	0.030 (2)	−0.0010 (16)	0.0047 (14)	−0.0006 (16)
C212	0.023 (2)	0.034 (2)	0.038 (2)	0.0002 (17)	0.0019 (16)	−0.0037 (18)
C213	0.023 (2)	0.039 (2)	0.034 (2)	−0.0003 (18)	−0.0005 (16)	−0.0073 (18)
C214	0.024 (2)	0.044 (3)	0.031 (2)	−0.0012 (18)	0.0010 (16)	−0.0009 (18)
C215	0.023 (2)	0.035 (2)	0.037 (2)	−0.0033 (17)	0.0035 (16)	−0.0011 (18)
C216	0.020 (2)	0.032 (2)	0.037 (2)	0.0001 (17)	0.0048 (16)	−0.0034 (17)
C217	0.046 (3)	0.044 (3)	0.038 (2)	−0.004 (2)	0.002 (2)	0.003 (2)

Geometric parameters (Å, º)

O1—C2	1.359 (4)	C7—C8	1.379 (5)
O1—C8A	1.387 (4)	C8—C8A	1.394 (5)
O2—C21	1.223 (4)	C8—H8	0.9500
O7—C7	1.358 (5)	C71—H71A	0.9800
O7—C71	1.450 (5)	C71—H71B	0.9800
O3—H3A	0.91 (6)	C71—H71C	0.9800
O4—C4	1.259 (5)	C211—C212	1.396 (5)
N2—C21	1.364 (5)	C211—C216	1.398 (5)
N2—C211	1.424 (5)	C212—C213	1.384 (6)
N2—H2	0.94 (5)	C212—H212	0.9500
C2—C3	1.352 (5)	C213—C214	1.404 (6)
C2—C21	1.503 (5)	C213—H213	0.9500
C3—C4	1.452 (5)	C214—C215	1.392 (5)
C3—H3	0.9500	C214—C217	1.507 (6)
C4—C4A	1.459 (5)	C215—C216	1.389 (5)
C4A—C8A	1.402 (6)	C215—H215	0.9500
C4A—C5	1.410 (5)	C216—H216	0.9500
C5—C6	1.377 (6)	C217—H21A	0.9800
C5—H5	0.9500	C217—H21B	0.9800
C6—C7	1.406 (6)	C217—H21C	0.9800
C6—H6	0.9500
C2—O1—C8A	118.9 (3)	O2—C21—C2	119.3 (3)
C7—O7—C71	117.5 (3)	N2—C21—C2	115.0 (3)
C21—N2—C211	127.1 (3)	O7—C71—H71A	109.5
C21—N2—H2	120 (3)	O7—C71—H71B	109.5
C211—N2—H2	113 (3)	H71A—C71—H71B	109.5
C3—C2—O1	123.9 (4)	O7—C71—H71C	109.5
C3—C2—C21	121.3 (3)	H71A—C71—H71C	109.5
O1—C2—C21	114.8 (3)	H71B—C71—H71C	109.5
C2—C3—C4	120.9 (4)	C212—C211—C216	119.2 (4)
C2—C3—H3	119.5	C212—C211—N2	124.7 (4)
C4—C3—H3	119.5	C216—C211—N2	116.1 (3)
O4—C4—C3	122.6 (4)	C213—C212—C211	119.5 (4)
O4—C4—C4A	122.6 (4)	C213—C212—H212	120.2
C3—C4—C4A	114.8 (4)	C211—C212—H212	120.2
C8A—C4A—C5	117.9 (4)	C212—C213—C214	122.0 (4)
C8A—C4A—C4	120.6 (4)	C212—C213—H213	119.0
C5—C4A—C4	121.4 (4)	C214—C213—H213	119.0
C6—C5—C4A	119.8 (4)	C215—C214—C213	117.8 (4)
C6—C5—H5	120.1	C215—C214—C217	120.6 (4)
C4A—C5—H5	120.1	C213—C214—C217	121.7 (4)
C5—C6—C7	120.6 (4)	C216—C215—C214	120.9 (4)
C5—C6—H6	119.7	C216—C215—H215	119.5
C7—C6—H6	119.7	C214—C215—H215	119.5
O7—C7—C8	124.8 (4)	C215—C216—C211	120.6 (4)
O7—C7—C6	114.1 (3)	C215—C216—H216	119.7
C8—C7—C6	121.1 (4)	C211—C216—H216	119.7
C7—C8—C8A	117.7 (4)	C214—C217—H21A	109.5
C7—C8—H8	121.2	C214—C217—H21B	109.5
C8A—C8—H8	121.2	H21A—C217—H21B	109.5
O1—C8A—C8	116.3 (3)	C214—C217—H21C	109.5
O1—C8A—C4A	120.9 (3)	H21A—C217—H21C	109.5
C8—C8A—C4A	122.8 (4)	H21B—C217—H21C	109.5
O2—C21—N2	125.6 (4)
C8A—O1—C2—C3	0.0 (5)	C5—C4A—C8A—O1	178.7 (3)
C8A—O1—C2—C21	−179.2 (3)	C4—C4A—C8A—O1	−2.6 (5)
O1—C2—C3—C4	−1.9 (6)	C5—C4A—C8A—C8	−0.7 (6)
C21—C2—C3—C4	177.2 (3)	C4—C4A—C8A—C8	177.9 (3)
C2—C3—C4—O4	−178.8 (4)	C211—N2—C21—O2	3.3 (6)
C2—C3—C4—C4A	1.5 (5)	C211—N2—C21—C2	−176.3 (3)
O4—C4—C4A—C8A	−179.0 (4)	C3—C2—C21—O2	12.0 (5)
C3—C4—C4A—C8A	0.7 (5)	O1—C2—C21—O2	−168.9 (3)
O4—C4—C4A—C5	−0.5 (6)	C3—C2—C21—N2	−168.4 (4)
C3—C4—C4A—C5	179.3 (3)	O1—C2—C21—N2	10.7 (4)
C8A—C4A—C5—C6	0.5 (5)	C21—N2—C211—C212	−9.3 (6)
C4—C4A—C5—C6	−178.1 (4)	C21—N2—C211—C216	170.7 (3)
C4A—C5—C6—C7	0.8 (6)	C216—C211—C212—C213	−1.1 (6)
C71—O7—C7—C8	0.8 (5)	N2—C211—C212—C213	178.9 (3)
C71—O7—C7—C6	−179.4 (3)	C211—C212—C213—C214	0.1 (6)
C5—C6—C7—O7	178.3 (3)	C212—C213—C214—C215	0.9 (6)
C5—C6—C7—C8	−1.9 (6)	C212—C213—C214—C217	−179.4 (4)
O7—C7—C8—C8A	−178.6 (3)	C213—C214—C215—C216	−0.9 (6)
C6—C7—C8—C8A	1.6 (6)	C217—C214—C215—C216	179.3 (4)
C2—O1—C8A—C8	−178.2 (3)	C214—C215—C216—C211	0.0 (6)
C2—O1—C8A—C4A	2.3 (5)	C212—C211—C216—C215	1.1 (6)
C7—C8—C8A—O1	−179.8 (3)	N2—C211—C216—C215	−178.9 (3)
C7—C8—C8A—C4A	−0.3 (6)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O1	0.94 (5)	2.28 (5)	2.661 (4)	103 (4)
N2—H2···O3	0.94 (5)	2.05 (5)	2.938 (4)	157 (4)
O3—H3A···O4^i	0.91 (6)	1.86 (6)	2.759 (4)	169 (6)
C212—H212···O2	0.95	2.31	2.906 (5)	120
C215—H215···O2^ii	0.95	2.53	3.422 (6)	157
C71—H71B···O2^iii	0.98	2.30	3.281 (5)	179

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

(3c) 7-Methoxy-4-oxo-N-p-tolyl-4H-chromene-2-carboxamide

Crystal data

C18H15NO4	Z = 2
Mr = 309.31	F(000) = 324
Triclinic, P1	Dx = 1.453 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71075 Å
a = 5.7544 (4) Å	Cell parameters from 8391 reflections
b = 8.0892 (5) Å	θ = 2.6–27.5°
c = 15.6269 (14) Å	µ = 0.10 mm^−1
α = 101.926 (7)°	T = 100 K
β = 95.366 (9)°	Plate, colourless
γ = 92.579 (9)°	0.15 × 0.08 × 0.02 mm
V = 707.04 (9) Å^3

Data collection

Rigaku Saturn724+ (2x2 bin mode) diffractometer	3231 independent reflections
Radiation source: Sealed Tube	2462 reflections with I > 2σ(I)
Graphite Monochromator monochromator	Rint = 0.034
Detector resolution: 28.5714 pixels mm^-1	θmax = 27.5°, θmin = 3.2°
profile data from ω–scans	h = −7→6
Absorption correction: multi-scan (CrystalClear-SM Expert; Rigaku, 2011)	k = −10→10
Tmin = 0.985, Tmax = 0.998	l = −20→20
9270 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.038	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.107	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	w = 1/[σ^2(Fo^2) + (0.0633P)^2] where P = (Fo^2 + 2Fc^2)/3
3231 reflections	(Δ/σ)max < 0.001
214 parameters	Δρmax = 0.30 e Å^−3
0 restraints	Δρmin = −0.28 e Å^−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
O1	0.55363 (13)	0.10681 (10)	0.33562 (5)	0.0139 (2)
O2	0.28332 (14)	0.07477 (10)	0.45625 (6)	0.0158 (2)
O4	1.16526 (14)	0.40505 (10)	0.38326 (6)	0.0161 (2)
O7	0.70519 (15)	−0.11505 (11)	0.04022 (6)	0.0199 (2)
N2	0.47324 (17)	0.29849 (12)	0.55660 (7)	0.0135 (2)
H2	0.591 (3)	0.376 (2)	0.5636 (11)	0.036 (4)*
C2	0.6222 (2)	0.20645 (14)	0.41634 (8)	0.0126 (3)
C3	0.8234 (2)	0.30408 (14)	0.43487 (8)	0.0142 (3)
H3	0.8618	0.3702	0.4927	0.017*
C4	0.9835 (2)	0.31137 (14)	0.36917 (8)	0.0129 (2)
C4A	0.9119 (2)	0.19883 (14)	0.28409 (8)	0.0128 (2)
C5	1.0474 (2)	0.18605 (15)	0.21300 (8)	0.0159 (3)
H5	1.1930	0.2502	0.2205	0.019*
C6	0.9733 (2)	0.08267 (15)	0.13315 (8)	0.0164 (3)
H6	1.0662	0.0760	0.0855	0.020*
C7	0.7583 (2)	−0.01370 (14)	0.12210 (8)	0.0152 (3)
C8	0.6189 (2)	−0.00433 (15)	0.18998 (8)	0.0149 (3)
H8	0.4732	−0.0685	0.1821	0.018*
C8A	0.6991 (2)	0.10268 (14)	0.27071 (8)	0.0130 (3)
C71	0.5029 (2)	−0.23012 (16)	0.02692 (9)	0.0235 (3)
H71A	0.4875	−0.2978	−0.0333	0.035*
H71B	0.3635	−0.1662	0.0363	0.035*
H71C	0.5190	−0.3053	0.0686	0.035*
C21	0.4414 (2)	0.18616 (14)	0.47828 (8)	0.0125 (2)
C211	0.3355 (2)	0.31018 (14)	0.62759 (8)	0.0123 (2)
C212	0.4144 (2)	0.43129 (15)	0.70350 (8)	0.0152 (3)
H212	0.5567	0.4971	0.7059	0.018*
C213	0.2860 (2)	0.45598 (15)	0.77530 (8)	0.0163 (3)
H213	0.3420	0.5392	0.8263	0.020*
C214	0.0766 (2)	0.36149 (15)	0.77444 (8)	0.0154 (3)
C215	0.0017 (2)	0.23956 (15)	0.69875 (8)	0.0153 (3)
H215	−0.1396	0.1729	0.6969	0.018*
C216	0.1270 (2)	0.21230 (15)	0.62581 (8)	0.0144 (3)
H216	0.0719	0.1280	0.5752	0.017*
C217	−0.0606 (2)	0.39025 (16)	0.85341 (8)	0.0206 (3)
H21A	−0.0228	0.5055	0.8880	0.031*
H21B	−0.0197	0.3086	0.8899	0.031*
H21C	−0.2284	0.3753	0.8337	0.031*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0123 (4)	0.0164 (4)	0.0112 (4)	−0.0027 (3)	0.0025 (3)	−0.0011 (3)
O2	0.0143 (4)	0.0156 (4)	0.0156 (4)	−0.0038 (3)	0.0019 (3)	−0.0002 (3)
O4	0.0130 (4)	0.0161 (4)	0.0180 (5)	−0.0048 (3)	0.0017 (3)	0.0016 (3)
O7	0.0204 (5)	0.0243 (5)	0.0121 (4)	−0.0062 (4)	0.0045 (4)	−0.0025 (4)
N2	0.0121 (5)	0.0136 (5)	0.0132 (5)	−0.0036 (4)	0.0022 (4)	−0.0002 (4)
C2	0.0142 (5)	0.0104 (5)	0.0123 (6)	0.0010 (4)	0.0002 (5)	0.0007 (4)
C3	0.0144 (6)	0.0138 (6)	0.0131 (6)	−0.0011 (5)	0.0007 (5)	0.0008 (5)
C4	0.0123 (5)	0.0109 (5)	0.0155 (6)	0.0007 (4)	0.0011 (5)	0.0031 (4)
C4A	0.0118 (5)	0.0124 (5)	0.0138 (6)	0.0009 (4)	0.0012 (5)	0.0021 (4)
C5	0.0135 (6)	0.0162 (6)	0.0177 (6)	−0.0014 (5)	0.0022 (5)	0.0028 (5)
C6	0.0155 (6)	0.0197 (6)	0.0142 (6)	−0.0003 (5)	0.0056 (5)	0.0023 (5)
C7	0.0179 (6)	0.0144 (6)	0.0119 (6)	0.0005 (5)	0.0007 (5)	0.0003 (5)
C8	0.0132 (6)	0.0152 (6)	0.0153 (6)	−0.0014 (5)	0.0007 (5)	0.0014 (5)
C8A	0.0129 (5)	0.0125 (6)	0.0140 (6)	0.0013 (4)	0.0029 (5)	0.0030 (5)
C71	0.0249 (7)	0.0252 (7)	0.0158 (6)	−0.0099 (6)	0.0018 (5)	−0.0031 (5)
C21	0.0113 (5)	0.0124 (5)	0.0137 (6)	0.0006 (4)	0.0011 (5)	0.0029 (4)
C211	0.0119 (5)	0.0130 (5)	0.0125 (6)	0.0014 (4)	0.0020 (4)	0.0033 (4)
C212	0.0136 (6)	0.0157 (6)	0.0153 (6)	−0.0024 (5)	0.0010 (5)	0.0020 (5)
C213	0.0181 (6)	0.0174 (6)	0.0118 (6)	−0.0003 (5)	0.0003 (5)	0.0006 (5)
C214	0.0149 (6)	0.0173 (6)	0.0154 (6)	0.0032 (5)	0.0031 (5)	0.0058 (5)
C215	0.0128 (5)	0.0164 (6)	0.0181 (6)	0.0000 (5)	0.0029 (5)	0.0068 (5)
C216	0.0137 (5)	0.0131 (5)	0.0155 (6)	−0.0007 (4)	0.0002 (5)	0.0023 (4)
C217	0.0195 (6)	0.0255 (7)	0.0174 (7)	0.0014 (5)	0.0055 (5)	0.0042 (5)

Geometric parameters (Å, º)

O1—C2	1.3619 (14)	C7—C8	1.3804 (17)
O1—C8A	1.3702 (14)	C8—C8A	1.3990 (16)
O2—C21	1.2237 (13)	C8—H8	0.9500
O4—C4	1.2383 (13)	C71—H71A	0.9800
O7—C7	1.3686 (14)	C71—H71B	0.9800
O7—C71	1.4290 (13)	C71—H71C	0.9800
N2—C21	1.3567 (15)	C211—C212	1.3971 (16)
N2—C211	1.4128 (16)	C211—C216	1.4022 (15)
N2—H2	0.885 (16)	C212—C213	1.3856 (17)
C2—C3	1.3451 (15)	C212—H212	0.9500
C2—C21	1.5116 (17)	C213—C214	1.3954 (16)
C3—C4	1.4500 (17)	C213—H213	0.9500
C3—H3	0.9500	C214—C215	1.3936 (17)
C4—C4A	1.4594 (16)	C214—C217	1.5100 (17)
C4A—C8A	1.3957 (15)	C215—C216	1.3900 (17)
C4A—C5	1.4051 (17)	C215—H215	0.9500
C5—C6	1.3694 (17)	C216—H216	0.9500
C5—H5	0.9500	C217—H21A	0.9800
C6—C7	1.4094 (16)	C217—H21B	0.9800
C6—H6	0.9500	C217—H21C	0.9800
C2—O1—C8A	118.47 (9)	O7—C71—H71B	109.5
C7—O7—C71	117.47 (9)	H71A—C71—H71B	109.5
C21—N2—C211	127.60 (10)	O7—C71—H71C	109.5
C21—N2—H2	116.6 (11)	H71A—C71—H71C	109.5
C211—N2—H2	115.8 (11)	H71B—C71—H71C	109.5
C3—C2—O1	123.13 (11)	O2—C21—N2	125.32 (11)
C3—C2—C21	127.35 (11)	O2—C21—C2	120.17 (10)
O1—C2—C21	109.51 (9)	N2—C21—C2	114.51 (10)
C2—C3—C4	121.89 (11)	C212—C211—C216	119.02 (11)
C2—C3—H3	119.1	C212—C211—N2	116.31 (10)
C4—C3—H3	119.1	C216—C211—N2	124.66 (11)
O4—C4—C3	123.36 (11)	C213—C212—C211	120.35 (10)
O4—C4—C4A	122.40 (11)	C213—C212—H212	119.8
C3—C4—C4A	114.24 (10)	C211—C212—H212	119.8
C8A—C4A—C5	117.83 (11)	C212—C213—C214	121.53 (11)
C8A—C4A—C4	119.81 (11)	C212—C213—H213	119.2
C5—C4A—C4	122.33 (10)	C214—C213—H213	119.2
C6—C5—C4A	121.15 (11)	C215—C214—C213	117.48 (11)
C6—C5—H5	119.4	C215—C214—C217	121.80 (11)
C4A—C5—H5	119.4	C213—C214—C217	120.72 (11)
C5—C6—C7	119.54 (11)	C216—C215—C214	122.14 (11)
C5—C6—H6	120.2	C216—C215—H215	118.9
C7—C6—H6	120.2	C214—C215—H215	118.9
O7—C7—C8	124.46 (10)	C215—C216—C211	119.47 (11)
O7—C7—C6	114.28 (11)	C215—C216—H216	120.3
C8—C7—C6	121.25 (11)	C211—C216—H216	120.3
C7—C8—C8A	117.88 (10)	C214—C217—H21A	109.5
C7—C8—H8	121.1	C214—C217—H21B	109.5
C8A—C8—H8	121.1	H21A—C217—H21B	109.5
O1—C8A—C4A	122.37 (10)	C214—C217—H21C	109.5
O1—C8A—C8	115.30 (10)	H21A—C217—H21C	109.5
C4A—C8A—C8	122.33 (11)	H21B—C217—H21C	109.5
O7—C71—H71A	109.5
C8A—O1—C2—C3	1.59 (16)	C5—C4A—C8A—C8	0.15 (18)
C8A—O1—C2—C21	−177.67 (9)	C4—C4A—C8A—C8	178.50 (11)
O1—C2—C3—C4	0.45 (18)	C7—C8—C8A—O1	−179.98 (10)
C21—C2—C3—C4	179.56 (10)	C7—C8—C8A—C4A	0.19 (18)
C2—C3—C4—O4	177.00 (11)	C211—N2—C21—O2	0.3 (2)
C2—C3—C4—C4A	−2.73 (17)	C211—N2—C21—C2	−179.42 (10)
O4—C4—C4A—C8A	−176.64 (11)	C3—C2—C21—O2	−169.33 (11)
C3—C4—C4A—C8A	3.09 (16)	O1—C2—C21—O2	9.88 (15)
O4—C4—C4A—C5	1.63 (18)	C3—C2—C21—N2	10.40 (18)
C3—C4—C4A—C5	−178.64 (10)	O1—C2—C21—N2	−170.38 (9)
C8A—C4A—C5—C6	0.00 (18)	C21—N2—C211—C212	176.18 (11)
C4—C4A—C5—C6	−178.30 (11)	C21—N2—C211—C216	−5.2 (2)
C4A—C5—C6—C7	−0.49 (19)	C216—C211—C212—C213	−1.08 (18)
C71—O7—C7—C8	−6.08 (18)	N2—C211—C212—C213	177.67 (11)
C71—O7—C7—C6	173.32 (10)	C211—C212—C213—C214	0.23 (19)
C5—C6—C7—O7	−178.56 (11)	C212—C213—C214—C215	0.63 (18)
C5—C6—C7—C8	0.86 (19)	C212—C213—C214—C217	179.96 (11)
O7—C7—C8—C8A	178.66 (11)	C213—C214—C215—C216	−0.67 (18)
C6—C7—C8—C8A	−0.70 (18)	C217—C214—C215—C216	−179.98 (11)
C2—O1—C8A—C4A	−1.12 (16)	C214—C215—C216—C211	−0.16 (18)
C2—O1—C8A—C8	179.05 (10)	C212—C211—C216—C215	1.04 (17)
C5—C4A—C8A—O1	−179.66 (10)	N2—C211—C216—C215	−177.59 (10)
C4—C4A—C8A—O1	−1.32 (17)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O4^i	0.885 (16)	2.178 (16)	3.0356 (12)	163.0 (16)
C3—H3···O4^i	0.95	2.39	3.2872 (15)	157
C6—H6···O7^ii	0.95	2.53	3.4669 (16)	169
C216—H216···O2	0.95	2.29	2.8957 (15)	121
C216—H216···O2^iii	0.95	2.51	3.2127 (14)	131
C212—H212···O4^i	0.95	2.43	3.2418 (15)	144

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