Synthesis and structures of three isoxazole-containing Schiff bases

Three {[(isoxazol-3-yl)imino]methyl}phenols were synthesized and structurally characterized. All three structures contain an intramolecular O—H⋯N hydrogen bond and none were found to be strongly thermochromic.


Introduction
A wide range of Schiff bases can be relatively easily prepared making them versatile as ligands and consequently they have found widespread use over many years in areas such as organometallic chemistry (Kargar et al., 2020), polymer synthesis (Mighani, 2020), anticancer drugs (Parveen, 2020), catalysts (Kumari et al., 2019) and sensors (Sahu et al., 2020). In addition, Schiff bases themselves have been found to display interesting properties with anils, i.e. Schiff bases of salicylaldehyde derivatives with aniline derivatives, having been first found to exhibit both thermo-and photochromism in the solid state (Senier et al., 1909;Cohen & Schmidt, 1962;Cohen et al., 1964). Originally, the thermo-and photochromism of anils were thought to be mutually exclusive (Cohen & Schmidt, 1962;Cohen et al., 1964), but this has since been found not to be the case and it is thought they all display thermochromism with some also displaying photochromism (Fujiwara et al., 2004). The colour change is believed to be due to a photo-or thermally induced tautomeric equilibrium shift between colourless enol(-imine) and keto(-amine) forms (Hadjoudis & Mavridis, 2004;Robert et al., 2009).

Synthesis
All reagents were used as supplied by Aldrich. Compounds were synthesized by direct condensation of the appropriate salicylaldehyde and isoxazole derivatives in ethanol. The salicylaldehyde (0.0025 mol) and aniline (0.0025 mol) were each dissolved in ethanol (25 ml). The resulting solutions were combined and refluxed with stirring for 6-8 h. Any precipitate was filtered off, rinsed with ethanol and left to dry. The (remaining) solution was then rotary evaporated until (further) precipitate formed. Recrystallization was carried out from hexane-dichloromethane for 1, ethanol for 2 or chloroform for 3 (see Scheme 1).

Characterization
Elemental C, H and N content analysis was carried out using the Durham University Analytical service on an Exeter Analytical E-440 Elemental Analyzer. Mass spectrometry in positive electrospray (ES+) mode was performed by the Durham University Mass Spectrometry service on a Waters TQD with an Acquity solvent system. Full details are available in the supporting information.

Refinement
All H atoms, apart from the hydroxy H atom involved in intramolecular hydrogen bonding with the imine N atom, were positioned geometrically and refined using a riding model. The H atoms involved in the intramolecular hydrogen bonding were located in a Fourier difference map wherever feasible.
Compounds 1 and 2 crystallized in noncentrosymmetric space groups; however, the Flack parameters obtained were not meaningful as the data were collected with molybdenum radiation and there are no heavy atoms to facilitate anomalous  dispersion. In 3, which contained two independent molecules in the asymmetric unit, one of the tert-butyl groups was disordered; the sum of the occupancies of the two parts was set to equal 1 and subsequently fixed at the refined values. The interplanar dihedral angle was calculated by measuring the angle between planes computed through the five or six non-H atoms of the two rings. See Table 1 for further details of the crystallographic data collections.

Structural discussion
The structures of 1-3 all consist of the same basic backbone with a hydroxy-substituted arene group joined to an isoxazole ring via an imine (C N) group (Fig. 1). The C7 N1 bond lengths are consistent with the presence of a double bond [ranging from 1.283 (2) Å in 1 to 1.293 (2) Å in 3], while the C1-O1 bond lengths [ranging from 1.350 (2) Å in 1 to 1.3655 (18) Å in 3] are consistent with a single bond. Indeed, the hydroxy H atom was located in a Fourier difference map in the vicinity of the O atom, supporting the fact that the structures are all in the more commonly observed enol form rather than the keto form. All three structures contain an intramolecular O1-H1Á Á ÁN1 hydrogen bond with similar parameters, e.g. the O1Á Á ÁN1 distances range from 2.6062 (17) to 2.632 (2) Å (Tables 2-4). The structures also contain weaker intermolecular C-HÁ Á ÁN and C-HÁ Á ÁO interactions (Tables 2-4).
Combining these interactions with thestacking creates a three-dimensional network with a herringbone-type packing structure (Fig. 2). The structure of 2 has shortstacking type interactions that exist between the six-membered aromatic ring and the C N group [centroid-to-centroid distance = 3.2772 (1) Å ], creating a one-dimensional stack approximately up the [101] direction. All the stacks in the ac plane are in the same direction; however, moving in the b-axis direction by one molecule, the stacks in the ac plane are in different directions due to the presence of the 2 1 screw axes and glide planes. The structure also contains: (i) C-HÁ Á ÁN and C-HÁ Á ÁO interactions involving the N and O atoms of isoxazole; (ii) C-HÁ Á ÁO interactions involving the O atom of the OH group. These interactions link the central molecule to four others, two on each side of the molecule, creating a three-dimensional network. An illustration of the overall packing is shown in Fig. 3.
In 3, the two independent molecules show slightly different intermolecular interactions: (i) C-HÁ Á ÁN (bifurcated for the isoxazole ring containing atoms N2 and O2, and not for the isoxazole ring containing atoms N4 and O4) and a C-HÁ Á ÁO interaction involving the N and O atoms of isoxazole; (ii) C-HÁ Á ÁO interactions involving the O atom of the OH group. This creates a three-dimensional packing network (Fig. 4).
There are nostacking type interactions between the sixmembered aromatic ring and the C N group in this case, presumably because of the presence of the bulky tert-butyl groups.

Chromic studies
The chromic behaviour of compounds 1-3 was not fully investigated herein; however, some observations are worth reporting given the similarity of the structures to the widely studied anils. Schiff bases of salicylaldehyde derivatives with aniline derivatives, which exhibit both thermo-and photochromism in the solid state (Cohen & Schmidt, 1962;Cohen et al., 1964;Fujiwara et al., 2004). In anils, a link has been proposed between the dihedral angle (È) and the chromic behaviour of some of the Schiff bases, with a suggestion that compounds with È < 25 are expected to be strongly thermochromic, while those with È > 25 are more likely to be photochromic (Hadjoudis & Mavridis, 2004;Robert et al., 2009). Clearly the dihedral angle is not the only factor that has been found to influence chromism in anils, with thermochromic structures tending to be more closely packed than  Table 4 Hydrogen-bond geometry (Å , ) for 3. Symmetry codes: (i) Àx; Ày þ 1; Àz; (ii) Àx þ 1; Ày þ 1; Àz; (iii) Àx; Ày; Àz.

Figure 2
Illustration of the packing in 1, looking down the b axis.  Illustration of the packing in 3, looking down the a axis.
photochromic structures and substituents that weaken the O-H bond or strengthen the accepting ability of the N atom often resulting in more strongly thermochromic complexes (Hadjoudis & Mavridis, 2004;Robert et al., 2009). The Schiff bases of salicylaldehyde derivatives with isoxazole derivatives presented here have not been widely studied in terms of their chromic behaviour and the three compounds presented herein appear to show some differences from the anils. The È value was 6.95 (12) for 1, 4.42 (14) for 2 and 6.53 (10)/14.27 (8) (two molecules) for 3; however, none of the compounds were observed to be strongly thermochromic by eye when cooled to $80 K. In the case of 2 and 3, this is perhaps not a major surprise as they are yellow at room temperature and, while they did become paler in colour at lower temperatures, the strongly thermochromic anil compounds are typically a red/ orange colour at room temperature and change to yellow upon cooling. However, 1, which is orange at room temperature, remained an orange colour at $80 K also. All three compounds did show evidence of photochromism with a colour change, from orange to red for 1 and from yellow to orange for 2 and 3, upon irradiation with UV light.

Refinement
Refinement on F 2 Least-squares matrix: full R[F 2 > 2σ(F 2 )] = 0.032 wR(F 2 ) = 0.083 S = 1.08 2166 reflections 131 parameters 0 restraints Primary atom site location: dual Hydrogen site location: mixed H atoms treated by a mixture of independent and constrained refinement where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.18 e Å −3 Δρ min = −0.14 e Å −3 sup-2 Acta Cryst. (2020). C76, 927-931 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.

(E)-2-{[(5-Methylisoxazol-3-yl)imino]methyl}phenol (2)
Crystal data where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.16 e Å −3 Δρ min = −0.17 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.

(E)-2,4-Di-tert-butyl-6-{[(isoxazol-3-yl)imino]methyl}phenol (3)
Crystal data 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.