Supra­molecular sheets in (4H-chromeno[4,3-c]isoxazol-3-yl)methanol and its hydrated 8-methyl-substituted analogue at 100 K

The title compounds, (4H-chromeno[4,3-c]isoxazol-3-yl)metha­nol, C₁₁H₉NO₃, (I), and (8-methyl-4H-chromeno[4,3-c]isoxazol-3-yl)methanol monohydrate, C₁₂H₁₁NO₃·H₂O, (II), crystallize in the monoclinic space groups P2₁/c and C2/c, respectively. The simple addition of a methyl substituent in (II) results in a change in the structure type and substantially alters the inter­molecular inter­action patterns, while retaining the point-group symmetry 2/m. Compound (II) crystallizes as a hydrate and the resulting hydrogen-bonding inter­actions involving the water mol­ecule are the cause of differences in the hydrogen-bonded supra­molecular motifs present in (I) and (II). The water mol­ecule in (II) is disordered over two positions having very similar orientations, with occupancies of 0.571 (18) and 0.429 (18), although the pattern of hydrogen-bonding inter­actions for the two disordered water mol­ecules remains essentially the same. In both compounds, the primary donor hy­droxy group adopts a trans conformation with respect to the isoxazole O atom, with a torsion angle of 170.65 (8)° for (I) and 179.56 (10)° for (II), the small difference being due to differences in the hydrogen-bonding environment of the hy­droxy group. In (I), mol­ecules are linked through two independent O-H...N and C-H...O hydrogen bonds and form sheets of centrosymmetric R₄⁴(18) and R₄⁴(14) rings extending parallel to the (100) plane. The supra­molecular motifs in (II) generate two-dimensional sheets parallel to the (100) plane through a combination of O-H...X (X = N, O) and C-H...O hydrogen bonds, leading to water-assisted noncentrosymmetric R₂²(8) and R₆⁶(20) motifs. The present work is an example of how the simple replacement of a substituent in the main mol­ecular scaffold may transform the structure type, paving the way for a variety of supra­molecular motifs and consequently altering the complexity of the inter­molecular inter­action patterns.

S1. Comment

Isoxazole derivatives are found to inhibit HIV-1 infection in human CD4+ lymphocytic T cells (Loh et al., 2010). They also possess antiviral (Lee & Kim, 2002) and anticonvulsant (Eddington et al., 2002) properties. The title compounds, namely (4H-chromeno[4,3-c]isoxazol-3-yl)methanol, (I), and (8-methyl-4H-chromeno[4,3-c]isoxazol-3-yl)methanol monohydrate, (II), are isoxazole derivatives which differ only by a methyl substituent in the benzene ring of the chroman. Although (I) and (II) differ only slightly in their hydrophobicity owing to the simple addition of a methyl group in (II), the crystal structures show striking differences in their molecular interaction patterns. We have recently reported the crystal structures of 9-fluoro-4H-chromeno[4,3-c]isoxazol-3-yl)methanol and its 9-chloro analogue, in which drastic differences in the molecular interaction patterns effected through the simple replacement of F by Cl were described (Rajalakshmi et al., 2012).

Both (I) and (II) crystallize in the monoclinic system in the space groups P2₁/c and C2/c, respectively. The addition of the hydrophobic methyl substituent has not caused a change in the point-group symmetry 2/m of the crystal structure but has substantially altered the intermolecular interactions in (II), as evidenced by an examination of its crystal packing. The presence of the water molecule at the interface between adjacent hydrophobic zones appears crucial for the stabilization of the crystal structure. However, there are no significant changes in the molecular conformation and the point-group symmetry of the structure remains unaltered. Crystals of (II) have water molecules incorporated in the structure and, in addition, as an unrelated but interesting observation, the ratio between the shortest and longest cell dimensions is 1.6 in (I) and 6.7 in (II), with the β angles being almost equal. The role of the water molecule in the hydrogen bonding and the differences it causes in determining supramolecular motifs in the crystal packing of (I) and (II) are discussed in the present paper.

The pyran ring adopts a skew-boat conformation with puckering parameters Q = 0.3992 (11) Å, θ = 114.32 (16)° and ϕ = 143.50 (17)° for (I), and Q = 0.3193 (13) Å, θ = 117.9 (3)° and ϕ = 144.4 (3)° for (II) (Cremer & Pople, 1975). The difference in the magnitude of the puckering is also evidenced by atoms C8 and O1 of the pyran ring deviating from the mean plane defined by the remaining atoms by 0.364 (2) and -0.229 (2) Å, respectively, for (I), and by -0.286 (2) and 0.20 (2)Å, respectively, for (II). The orientation of hydroxy atom O3 with respect to isoxazole atom O2 is described by the O2—C10—C11—O3 torsion angles of 170.65 (8)° for (I) and 179.6 (1)° for (II), indicating an antiperiplanar conformation. The respective conformation and deviations from the ideal value of 180° in (I) and (II) may be attributed to the significant difference in the mode of participation of atom O3 in hydrogen bonding, i.e. O3 participates in an O—H···N hydrogen bond in (I) (Table 1) and in O—H···N and O—H···O hydrogen bonds in (II).

In (II), the water molecule exhibits disorder, which was modelled using two sets of atomic sites with refined occupancies of 0.57 (2) and 0.43 (2) (Fig. 2). The O1W···O11W separation between the major and minor disordered components is 0.5870 Å, and the angle between the planes formed by the respective components is 37.37°. A nonbonded interaction involving the minor disordered component [O11W···O11W(-x + 2, y, -z + 3/2) = 2.787 (1) Å] across a twofold rotation axis is observed. The hydrogen-bonding environments of both O1W and O11W are essentially identical, with the O—H···N hydrogen bond deviating significantly from linearity. C—H···O hydrogen bonds involving both O1W and O11W are also present (Table 2). The C8···O11W and H8A···O11W distances involving the minor component are noticeably longer [3.66 (1) and 2.74 (1) Å, respectively] than those of the major component [3.513 (7) and 2.576 (7) Å, respectively]. This type of disorder in the water molecule has a significant impact on the supramolecular architecture of (II). The major component O1W is involved in O—H···O, C—H···O and O—H···N hydrogen bonds and forms supramolecular R₁²(8) and R₆⁶(20) motifs (Bernstein et al., 1995) extending along c axis.

The hydrogen-bonded networks of (I) and (II) are formed by a combination of O—H···N, O—H···O and C—H···O hydrogen-bonded supramolecular motifs. In (I), an O3—H3···N1ⁱ [symmetry code: (i) x, -y + 1/2, z + 1/2] hydrogen-bonded C(6) motif links 2₁ screw-related molecules into a linear chain parallel to the [001] direction (Fig. 3). Each linear chain is linked to its adjacent antiparallel pair through C11—H11A···O3ⁱⁱ [symmetry code: (ii) -x + 1, y - 1/2, -z + 3/2] hydrogen-bonded C(3) motifs. The C(3) and C(6) motifs along the b and c axes, respectively, are the fundamental linking units in the formation of a supramolecular two-dimensional corrugated sheet parallel to the [011] direction characterized by R₄⁴(16) and R₄⁴(36) motifs (Fig. 4). In addition, the C(6) chain and its inversion-related pair are connected through π–π interactions between the isoxazole rings, with a ring-centroid separation of 3.7063 (6) Å, an interplanar spacing of ca 3.60 Å and a ring offset of ca 0.76 Å. The absence of O—H···O hydrogen bonds in the molecular interaction pattern, in spite of there being enough scope due to the presence of three O atoms in the molecule, is significant in the context of the prediction of intermolecular interaction patterns. While hydroxy atom O3 participates as both an acceptor and a donor in hydrogen bonds, atom O1 is involved in a nonbonded O1···O1(-x, -y + 1, -z + 1) contact of 3.119 (1) Å.

In (II), the presence of a water molecule in the structure seems to be crucial for the stabilization of the molecular structure, as evidenced from its participation in four hydrogen bonds. The environment surrounding water atom O1W is far from being tetrahedral and seems similar to that of over-coordinated oxygen (OCO), with O1W participating in two `acceptor bonds' and two `donor bonds' (Fig. 5) (Markovitch & Agmon, 2008). Atom O3 participates in two O—H···O hydrogen bonds, as both a donor [O3—H3···O1Wⁱ; symmetry code: (i) x, y + 1, z] and as an acceptor (O1W—H2W···O3). The hydroxy `acceptor bonds', together with an intramolecular C8—H8B···O1W hydrogen bond, lead to the formation of an R₁² (8) motif. Water atom O1W is shared by O1W—H1W···N1ⁱⁱ [symmetry code: (ii) x, -y + 2, z - 1/2] and O1W—H2W···O3 bonds, leading to C₁²(8) one-dimensional chains along the c axis (Fig. 6). Each such chain is linked to its adjacent parallel pair through an O3—H3···O1Wⁱ hydrogen bond between water atom O1W and hydroxy atom O3, leading to the formation of a two-dimensional supramolecular sheet parallel to the (011) plane characterized by an R₆⁶ (20) motif (Fig. 7). In addition, two nonbonded interactions, viz. O2···O2(-x, -1 - y, -z) of 2.919 (1) Å and O2···O2(-x + 2, -y + 2, -z + 2) of 3.087 (1) Å, are observed. A weak π–π interaction exists between the isoxazole ring at (x, y, z) and the benzene ring at (x, y + 1, z), corresponding to a ring-centroid separation of 3.8007 (10) Å, an interplanar spacing of ca 3.56 Å and a ring offset of ca 1.74 Å. These interactions generate π-stacked chains running parallel to the [010] direction (Fig. 8).

In both (I) and (II), atoms O1 and O2 do not participate in intermolecular interactions, except for an O1···O1 nonbonded contact in (I) and an O2···O2 contact in (II). In (II), it is pertinent to note that all the hydrogen bonds are linked through water, and this possibly indicates the necessity for it to be present in the structure. The present work is an example of how the simple addition of a methyl substituent to the main molecular scaffold, while retaining the point-group symmetry, may pave the way for a variety of supramolecular motifs, transforming the structure type and consequently altering the complexity of the intermolecular interaction patterns.

Related literature

For related literature, see: Bernstein et al. (1995); Cremer & Pople (1975); Eddington et al. (2002); Lee & Kim (2002); Liaskopoulos et al. (2007); Loh et al. (2010); Markovitch & Agmon (2008); Rajalakshmi et al. (2012).

S2. Experimental

Samples of (I) and (II) were prepared according to the procedure of Liaskopoulos et al. (2007), starting from 2-hydroxybenzaldehyde or 2-hydroxy-5-methylbenzaldehyde with 4-chlorobut-2-yn-1-ol in equimolar amounts. Crystals suitable for single-crystal X-ray diffraction were grown by slow evaporation from solutions in ethanol.

The crystal of (I) was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100 (2)K.

S3. Refinement

In (I), the hydroxy H atom was located in a difference map and refined freely. All other H atoms were placed geometrically and treated as riding, with C—H = 0.95 Å (aromatic) and U_iso(H) = 1.2U_eq(C). In (II), all the H atoms (other than the water H atoms) were placed geometrically and treated as riding, with C—H = 0.95 (aromatic) or 0.99 Å (methylene) and U_iso(H) = 1.2U_eq(C). The water molecule is disordered, with site occupancies of 0.571 (18) and 0.429 (18). The water H atoms were located from difference Fourier maps but were restrained to O—H = 0.85 Å, and H···H distances between the major and minor components were treated using SADI instructions [Please restate in software-independent terms], allowing them to ride on their respective parent atom with U_iso(H) = 1.5U_eq(O).

Computing details

For both compounds, data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures

	Fig. 1. The molecular structure of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. The molecular structure of (II), showing the atom-labelling scheme. O1W/H1W/H2W and O11W/H11W/H22W are the major and minor components of the water molecule, respectively. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 3. Part of the crystal structure of (I), showing the formation of an O—H···N hydrogen bond (dashed lines) which links the molecules into a C(6) chain along the c axis. For the sake of clarity, H atoms not involved in the hydrogen-bonding motif shown have been omitted.
	Fig. 4. Part of the crystal structure of (I), showing the formation of a supramolecular sheets of edge-fused R4^4(16) and R4^4(36) rings parallel to the [011] direction. Dashed lines indicate hydrogen bonds. For the sake of clarity, H atoms bonded to C atoms have been omitted.
	Fig. 5. Part of the crystal structure of (II), showing the hydrogen bonding (dashed lines) around the water molecule. R1^2(8) motifs are formed through a combination of O—H···O and C—H···O, and O—H···N and C—H···O, hydrogen bonds. For the sake of clarity, H atoms not involved in the motifs shown have been omitted. [Symmetry code: (a) Please provide.]
	Fig. 6. Part of the crystal structure of (II), showing the formation of a C1^2(8) chain running parallel to the c axis. Dashed lines indicate hydrogen bonds.
	Fig. 7. Part of the crystal structure of (II), showing the formation of the two-dimensional sheet of the supramolecular network. For the sake of clarity, H atoms bonded to C atoms have been omitted. Dashed lines indicate hydrogen bonds.
	Fig. 8. Part of the crystal structure of (II), showing the formation of π-stacked chains running along [010]. The centroids of the isoxazole and benzene rings (Cg1 and Cg2, respectively) are indicated with small spheres. Dashed lines indicate hydrogen bonds. For the sake of clarity, H atoms not involved in the interactions shown have been omitted.

(I) (4H-Chromeno[4,3-c]isoxazol-3-yl)methanol

Crystal data

C11H9NO3	F(000) = 424
Mr = 203.19	Dx = 1.493 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 2956 reflections
a = 9.6423 (2) Å	θ = 2.7–31.5°
b = 8.3406 (1) Å	µ = 0.11 mm^−1
c = 13.1461 (2) Å	T = 100 K
β = 121.218 (1)°	Block, colourless
V = 904.16 (3) Å^3	0.38 × 0.22 × 0.06 mm
Z = 4

Data collection

Bruker SMART APEXII CCD area-detector diffractometer	3743 independent reflections
Radiation source: fine-focus sealed tube	2956 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.030
ϕ and ω scans	θmax = 34.2°, θmin = 2.5°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −15→11
Tmin = 0.971, Tmax = 0.993	k = −13→12
14247 measured reflections	l = −20→20

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)] = 0.045	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.120	H-atom parameters constrained
S = 1.04	w = 1/[σ^2(Fo^2) + (0.0607P)^2 + 0.2418P] where P = (Fo^2 + 2Fc^2)/3
3743 reflections	(Δ/σ)max < 0.001
136 parameters	Δρmax = 0.58 e Å^−3
0 restraints	Δρmin = −0.28 e Å^−3

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100 (2)K (1) K. Cosier, J. & Glazer, A. M. (1986). J. Appl. Cryst. 19, 105–107.

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	0.06136 (9)	0.44242 (9)	0.41723 (6)	0.01613 (15)
O2	0.55740 (9)	0.22910 (9)	0.56470 (6)	0.01662 (15)
O3	0.51567 (9)	0.44947 (9)	0.78401 (7)	0.01745 (15)
H3	0.5008	0.4019	0.8360	0.026*
N1	0.45316 (10)	0.22839 (11)	0.43995 (7)	0.01659 (17)
C1	0.33012 (11)	0.31989 (11)	0.41987 (8)	0.01312 (16)
C2	0.18522 (11)	0.35464 (11)	0.30568 (8)	0.01320 (17)
C3	0.16741 (12)	0.32326 (12)	0.19477 (8)	0.01553 (18)
H3A	0.2564	0.2827	0.1906	0.019*
C4	0.02032 (13)	0.35123 (12)	0.09120 (9)	0.01709 (19)
H4A	0.0080	0.3293	0.0160	0.021*
C5	−0.10995 (12)	0.41179 (12)	0.09773 (9)	0.01786 (19)
H5A	−0.2107	0.4310	0.0266	0.021*
C6	−0.09396 (12)	0.44429 (12)	0.20694 (9)	0.01660 (18)
H6A	−0.1833	0.4852	0.2105	0.020*
C7	0.05389 (11)	0.41660 (11)	0.31120 (8)	0.01349 (17)
C8	0.21731 (11)	0.48962 (12)	0.51724 (9)	0.01482 (17)
H8A	0.2147	0.4843	0.5914	0.018*
H8B	0.2416	0.6015	0.5064	0.018*
C9	0.34623 (11)	0.38035 (11)	0.52650 (8)	0.01245 (16)
C10	0.48983 (11)	0.32032 (11)	0.61385 (8)	0.01306 (16)
C11	0.58585 (12)	0.33159 (12)	0.74621 (8)	0.01494 (17)
H11A	0.5865	0.2264	0.7814	0.018*
H11B	0.6993	0.3611	0.7734	0.018*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0125 (3)	0.0234 (4)	0.0140 (3)	0.0010 (2)	0.0079 (3)	−0.0016 (3)
O2	0.0147 (3)	0.0213 (3)	0.0139 (3)	0.0048 (3)	0.0074 (3)	0.0004 (2)
O3	0.0234 (4)	0.0165 (3)	0.0164 (3)	0.0006 (3)	0.0131 (3)	0.0001 (2)
N1	0.0152 (4)	0.0221 (4)	0.0130 (3)	0.0037 (3)	0.0077 (3)	−0.0003 (3)
C1	0.0132 (4)	0.0149 (4)	0.0134 (4)	0.0005 (3)	0.0084 (3)	0.0002 (3)
C2	0.0134 (4)	0.0139 (4)	0.0131 (4)	0.0004 (3)	0.0074 (3)	0.0005 (3)
C3	0.0170 (4)	0.0172 (4)	0.0143 (4)	0.0001 (3)	0.0094 (3)	−0.0003 (3)
C4	0.0202 (4)	0.0177 (4)	0.0127 (4)	−0.0023 (3)	0.0080 (3)	−0.0008 (3)
C5	0.0156 (4)	0.0183 (4)	0.0152 (4)	−0.0015 (3)	0.0048 (3)	−0.0003 (3)
C6	0.0126 (4)	0.0183 (4)	0.0174 (4)	0.0004 (3)	0.0067 (3)	−0.0008 (3)
C7	0.0132 (4)	0.0145 (4)	0.0137 (4)	−0.0003 (3)	0.0077 (3)	−0.0003 (3)
C8	0.0137 (4)	0.0165 (4)	0.0143 (4)	0.0021 (3)	0.0072 (3)	−0.0013 (3)
C9	0.0134 (4)	0.0132 (4)	0.0132 (4)	0.0005 (3)	0.0086 (3)	0.0002 (3)
C10	0.0133 (4)	0.0139 (4)	0.0142 (4)	0.0004 (3)	0.0087 (3)	0.0003 (3)
C11	0.0153 (4)	0.0156 (4)	0.0132 (4)	0.0007 (3)	0.0069 (3)	0.0006 (3)

Geometric parameters (Å, º)

O1—C7	1.3749 (12)	C4—C5	1.3971 (15)
O1—C8	1.4475 (12)	C4—H4A	0.9500
O2—C10	1.3628 (12)	C5—C6	1.3890 (14)
O2—N1	1.4111 (11)	C5—H5A	0.9500
O3—C11	1.4213 (12)	C6—C7	1.3924 (13)
O3—H3	0.8643	C6—H6A	0.9500
N1—C1	1.3173 (12)	C8—C9	1.4945 (13)
C1—C9	1.4205 (13)	C8—H8A	0.9900
C1—C2	1.4545 (13)	C8—H8B	0.9900
C2—C3	1.4015 (13)	C9—C10	1.3559 (13)
C2—C7	1.4040 (13)	C10—C11	1.4912 (13)
C3—C4	1.3850 (14)	C11—H11A	0.9900
C3—H3A	0.9500	C11—H11B	0.9900
C7—O1—C8	116.57 (8)	O1—C7—C6	117.44 (9)
C10—O2—N1	109.02 (7)	O1—C7—C2	122.37 (8)
C11—O3—H3	105.3	C6—C7—C2	120.06 (9)
C1—N1—O2	104.80 (7)	O1—C8—C9	109.68 (8)
N1—C1—C9	112.43 (8)	O1—C8—H8A	109.7
N1—C1—C2	127.29 (9)	C9—C8—H8A	109.7
C9—C1—C2	120.20 (8)	O1—C8—H8B	109.7
C3—C2—C7	119.68 (9)	C9—C8—H8B	109.7
C3—C2—C1	124.80 (9)	H8A—C8—H8B	108.2
C7—C2—C1	115.44 (8)	C10—C9—C1	104.24 (8)
C4—C3—C2	120.14 (9)	C10—C9—C8	137.34 (9)
C4—C3—H3A	119.9	C1—C9—C8	118.37 (8)
C2—C3—H3A	119.9	C9—C10—O2	109.51 (8)
C3—C4—C5	119.72 (9)	C9—C10—C11	135.14 (9)
C3—C4—H4A	120.1	O2—C10—C11	115.35 (8)
C5—C4—H4A	120.1	O3—C11—C10	109.36 (8)
C6—C5—C4	120.82 (9)	O3—C11—H11A	109.8
C6—C5—H5A	119.6	C10—C11—H11A	109.8
C4—C5—H5A	119.6	O3—C11—H11B	109.8
C5—C6—C7	119.58 (9)	C10—C11—H11B	109.8
C5—C6—H6A	120.2	H11A—C11—H11B	108.3
C7—C6—H6A	120.2
C10—O2—N1—C1	0.81 (10)	C3—C2—C7—C6	0.99 (14)
O2—N1—C1—C9	−0.90 (11)	C1—C2—C7—C6	−175.87 (9)
O2—N1—C1—C2	−177.60 (9)	C7—O1—C8—C9	−48.39 (11)
N1—C1—C2—C3	−14.11 (16)	N1—C1—C9—C10	0.66 (11)
C9—C1—C2—C3	169.42 (9)	C2—C1—C9—C10	177.63 (8)
N1—C1—C2—C7	162.58 (10)	N1—C1—C9—C8	178.48 (9)
C9—C1—C2—C7	−13.90 (13)	C2—C1—C9—C8	−4.55 (13)
C7—C2—C3—C4	−0.86 (14)	O1—C8—C9—C10	−148.72 (11)
C1—C2—C3—C4	175.70 (9)	O1—C8—C9—C1	34.40 (12)
C2—C3—C4—C5	0.39 (15)	C1—C9—C10—O2	−0.11 (10)
C3—C4—C5—C6	−0.06 (15)	C8—C9—C10—O2	−177.28 (11)
C4—C5—C6—C7	0.19 (15)	C1—C9—C10—C11	179.97 (10)
C8—O1—C7—C6	−151.03 (9)	C8—C9—C10—C11	2.8 (2)
C8—O1—C7—C2	33.13 (13)	N1—O2—C10—C9	−0.42 (11)
C5—C6—C7—O1	−176.60 (9)	N1—O2—C10—C11	179.52 (8)
C5—C6—C7—C2	−0.66 (15)	C9—C10—C11—O3	−9.43 (16)
C3—C2—C7—O1	176.73 (9)	O2—C10—C11—O3	170.65 (8)
C1—C2—C7—O1	−0.14 (13)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···N1^i	0.86	1.98	2.8367 (11)	173
C11—H11A···O3^ii	0.99	2.48	3.2970 (12)	139

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

(II) (8-Methyl-4H-chromeno[4,3-c]isoxazol-3-yl)methanol monohydrate

Crystal data

C12H11NO3·H2O	F(000) = 992
Mr = 235.23	Dx = 1.443 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 2770 reflections
a = 31.2492 (5) Å	θ = 1.5–32.5°
b = 4.6714 (1) Å	µ = 0.11 mm^−1
c = 17.3083 (4) Å	T = 100 K
β = 121.030 (2)°	Block, colourless
V = 2165.06 (8) Å^3	0.38 × 0.14 × 0.09 mm
Z = 8

Data collection

Bruker SMART APEXII CCD area-detector diffractometer	3852 independent reflections
Radiation source: fine-focus sealed tube	3028 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.040
ϕ and ω scans	θmax = 32.5°, θmin = 1.5°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −46→46
Tmin = 0.982, Tmax = 0.990	k = −6→6
25453 measured reflections	l = −26→26

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)] = 0.051	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.133	H-atom parameters constrained
S = 1.02	w = 1/[σ^2(Fo^2) + (0.0649P)^2 + 1.7458P] where P = (Fo^2 + 2Fc^2)/3
3852 reflections	(Δ/σ)max = 0.001
166 parameters	Δρmax = 0.42 e Å^−3
0 restraints	Δρmin = −0.35 e Å^−3

Special details

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

Refinement. Refinement of 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	Occ. (<1)
O1	0.84189 (3)	0.69155 (19)	0.76621 (6)	0.01794 (19)
O2	0.96508 (3)	1.26156 (19)	0.97468 (6)	0.01735 (19)
O3	0.94331 (4)	1.3327 (3)	0.74896 (6)	0.0317 (3)
H3	0.9459	1.4751	0.7220	0.048*
N1	0.93733 (4)	1.0989 (2)	1.00266 (7)	0.0173 (2)
C1	0.90132 (4)	0.9813 (2)	0.92860 (8)	0.0149 (2)
C2	0.86272 (4)	0.7885 (2)	0.92054 (8)	0.0144 (2)
C3	0.85405 (4)	0.7253 (3)	0.99037 (8)	0.0168 (2)
H3A	0.8738	0.8163	1.0472	0.020*
C4	0.81731 (4)	0.5328 (3)	0.97848 (8)	0.0173 (2)
C5	0.78845 (5)	0.4040 (3)	0.89353 (8)	0.0189 (2)
H5	0.7629	0.2731	0.8838	0.023*
C6	0.79642 (4)	0.4637 (3)	0.82328 (8)	0.0179 (2)
H6	0.7765	0.3737	0.7664	0.021*
C7	0.83367 (4)	0.6558 (2)	0.83656 (8)	0.0149 (2)
C8	0.86360 (4)	0.9585 (3)	0.76012 (8)	0.0165 (2)
H8A	0.8373	1.1067	0.7324	0.020*
H8B	0.8778	0.9319	0.7210	0.020*
C9	0.90369 (4)	1.0563 (2)	0.85134 (7)	0.0143 (2)
C10	0.94405 (4)	1.2302 (2)	0.88400 (8)	0.0150 (2)
C11	0.96897 (5)	1.3874 (3)	0.84262 (8)	0.0169 (2)
H11A	0.9688	1.5955	0.8534	0.020*
H11B	1.0041	1.3240	0.8707	0.020*
C12	0.80931 (5)	0.4640 (3)	1.05530 (9)	0.0230 (3)
H12A	0.8385	0.5260	1.1123	0.034*
H12B	0.8048	0.2571	1.0572	0.034*
H12C	0.7795	0.5641	1.0463	0.034*
O1W	0.9355 (2)	0.7877 (15)	0.6637 (2)	0.0254 (9)	0.571 (18)
H1W	0.9358	0.8326	0.6165	0.038*	0.571 (18)
H2W	0.9446	0.9123	0.7046	0.038*	0.571 (18)
O11W	0.9505 (3)	0.8795 (16)	0.6793 (4)	0.0253 (12)	0.429 (18)
H11W	0.9601	0.8401	0.6427	0.038*	0.429 (18)
H22W	0.9414	1.0419	0.6835	0.038*	0.429 (18)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0238 (4)	0.0198 (4)	0.0140 (4)	−0.0053 (3)	0.0124 (4)	−0.0027 (3)
O2	0.0214 (4)	0.0208 (4)	0.0134 (4)	−0.0064 (3)	0.0114 (3)	−0.0014 (3)
O3	0.0400 (6)	0.0457 (7)	0.0155 (5)	−0.0202 (5)	0.0186 (4)	−0.0069 (4)
N1	0.0208 (5)	0.0200 (5)	0.0152 (5)	−0.0052 (4)	0.0122 (4)	−0.0002 (4)
C1	0.0179 (5)	0.0160 (5)	0.0130 (5)	−0.0003 (4)	0.0097 (4)	0.0003 (4)
C2	0.0160 (5)	0.0157 (5)	0.0132 (5)	−0.0007 (4)	0.0087 (4)	0.0001 (4)
C3	0.0187 (5)	0.0198 (5)	0.0136 (5)	−0.0012 (4)	0.0095 (4)	0.0005 (4)
C4	0.0175 (5)	0.0205 (5)	0.0161 (5)	0.0001 (4)	0.0102 (4)	0.0026 (4)
C5	0.0169 (5)	0.0203 (6)	0.0202 (6)	−0.0026 (4)	0.0102 (5)	0.0007 (4)
C6	0.0174 (5)	0.0195 (5)	0.0165 (5)	−0.0023 (4)	0.0085 (4)	−0.0011 (4)
C7	0.0167 (5)	0.0167 (5)	0.0130 (5)	0.0003 (4)	0.0089 (4)	0.0007 (4)
C8	0.0196 (5)	0.0188 (5)	0.0134 (5)	−0.0032 (4)	0.0101 (4)	−0.0004 (4)
C9	0.0175 (5)	0.0150 (5)	0.0121 (5)	−0.0005 (4)	0.0089 (4)	0.0000 (4)
C10	0.0194 (5)	0.0156 (5)	0.0127 (5)	−0.0002 (4)	0.0101 (4)	0.0003 (4)
C11	0.0211 (6)	0.0184 (5)	0.0149 (5)	−0.0025 (4)	0.0119 (5)	0.0001 (4)
C12	0.0234 (6)	0.0302 (7)	0.0194 (6)	−0.0034 (5)	0.0139 (5)	0.0036 (5)
O1W	0.0385 (17)	0.0249 (19)	0.0168 (10)	−0.0005 (14)	0.0171 (11)	−0.0012 (10)
O11W	0.048 (3)	0.0181 (19)	0.0182 (15)	−0.001 (2)	0.0228 (17)	−0.0012 (14)

Geometric parameters (Å, º)

O1—C7	1.3779 (14)	C8—C9	1.4940 (16)
O1—C8	1.4493 (14)	C8—H8A	0.9900
O2—C10	1.3613 (14)	C8—H8B	0.9900
O2—N1	1.4130 (12)	C9—C10	1.3544 (16)
O3—C11	1.4129 (15)	C10—C11	1.4948 (16)
O3—H3	0.8400	C11—H11A	0.9900
N1—C1	1.3130 (15)	C11—H11B	0.9900
C1—C9	1.4208 (15)	C12—H12A	0.9800
C1—C2	1.4536 (16)	C12—H12B	0.9800
C2—C3	1.3993 (16)	C12—H12C	0.9800
C2—C7	1.4002 (16)	O1W—H1W	0.8472
C3—C4	1.3878 (16)	O1W—H2W	0.8449
C3—H3A	0.9500	O1W—H11W	1.0329
C4—C5	1.4036 (18)	O1W—H22W	1.2232
C4—C12	1.5087 (16)	O11W—H1W	0.9623
C5—C6	1.3895 (17)	O11W—H2W	0.5751
C5—H5	0.9500	O11W—H11W	0.8498
C6—C7	1.3917 (16)	O11W—H22W	0.8256
C6—H6	0.9500
C7—O1—C8	118.43 (9)	C9—C8—H8B	109.5
C10—O2—N1	108.69 (9)	H8A—C8—H8B	108.1
C11—O3—H3	109.5	C10—C9—C1	104.13 (10)
C1—N1—O2	105.00 (9)	C10—C9—C8	135.85 (10)
N1—C1—C9	112.42 (10)	C1—C9—C8	119.81 (10)
N1—C1—C2	127.17 (10)	C9—C10—O2	109.75 (10)
C9—C1—C2	120.39 (10)	C9—C10—C11	134.25 (11)
C3—C2—C7	119.53 (11)	O2—C10—C11	116.00 (10)
C3—C2—C1	124.62 (11)	O3—C11—C10	109.46 (10)
C7—C2—C1	115.83 (10)	O3—C11—H11A	109.8
C4—C3—C2	121.48 (11)	C10—C11—H11A	109.8
C4—C3—H3A	119.3	O3—C11—H11B	109.8
C2—C3—H3A	119.3	C10—C11—H11B	109.8
C3—C4—C5	117.95 (11)	H11A—C11—H11B	108.2
C3—C4—C12	120.52 (11)	C4—C12—H12A	109.5
C5—C4—C12	121.53 (11)	C4—C12—H12B	109.5
C6—C5—C4	121.50 (11)	H12A—C12—H12B	109.5
C6—C5—H5	119.2	C4—C12—H12C	109.5
C4—C5—H5	119.2	H12A—C12—H12C	109.5
C5—C6—C7	119.79 (11)	H12B—C12—H12C	109.5
C5—C6—H6	120.1	H1W—O1W—H2W	118.1
C7—C6—H6	120.1	H2W—O1W—H11W	98.2
O1—C7—C6	116.95 (10)	H1W—O1W—H22W	87.5
O1—C7—C2	123.19 (10)	H11W—O1W—H22W	80.7
C6—C7—C2	119.74 (10)	H1W—O11W—H2W	140.2
O1—C8—C9	110.80 (9)	H2W—O11W—H11W	176.6
O1—C8—H8A	109.5	H1W—O11W—H22W	108.9
C9—C8—H8A	109.5	H2W—O11W—H22W	55.3
O1—C8—H8B	109.5	H11W—O11W—H22W	122.3
C10—O2—N1—C1	−0.50 (12)	C1—C2—C7—O1	2.99 (17)
O2—N1—C1—C9	0.41 (13)	C3—C2—C7—C6	0.24 (17)
O2—N1—C1—C2	178.83 (11)	C1—C2—C7—C6	178.85 (11)
N1—C1—C2—C3	8.7 (2)	C7—O1—C8—C9	40.06 (14)
C9—C1—C2—C3	−173.03 (11)	N1—C1—C9—C10	−0.17 (14)
N1—C1—C2—C7	−169.87 (12)	C2—C1—C9—C10	−178.71 (10)
C9—C1—C2—C7	8.44 (16)	N1—C1—C9—C8	−175.75 (11)
C7—C2—C3—C4	0.22 (18)	C2—C1—C9—C8	5.71 (17)
C1—C2—C3—C4	−178.26 (11)	O1—C8—C9—C10	157.34 (13)
C2—C3—C4—C5	−0.63 (18)	O1—C8—C9—C1	−28.81 (15)
C2—C3—C4—C12	178.83 (12)	C1—C9—C10—O2	−0.16 (13)
C3—C4—C5—C6	0.61 (18)	C8—C9—C10—O2	174.33 (13)
C12—C4—C5—C6	−178.85 (12)	C1—C9—C10—C11	179.91 (13)
C4—C5—C6—C7	−0.17 (19)	C8—C9—C10—C11	−5.6 (2)
C8—O1—C7—C6	154.93 (11)	N1—O2—C10—C9	0.41 (13)
C8—O1—C7—C2	−29.11 (16)	N1—O2—C10—C11	−179.65 (10)
C5—C6—C7—O1	175.85 (11)	C9—C10—C11—O3	−0.52 (19)
C5—C6—C7—C2	−0.26 (18)	O2—C10—C11—O3	179.56 (10)
C3—C2—C7—O1	−175.62 (11)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1W—H2W···O3	0.84	2.12	2.889 (7)	152
O11W—H22W···O3	0.83	1.75	2.502 (6)	151
O3—H3···O1W^i	0.84	1.71	2.527 (6)	164
O3—H3···O11W^i	0.84	2.06	2.882 (8)	166
O1W—H1W···N1^ii	0.85	2.02	2.866 (3)	175
O11W—H11W···N1^ii	0.85	2.16	2.870 (3)	140
C8—H8B···O1W	0.99	2.56	3.513 (3)	162

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