Crystal structure of 5-(4-tert-butoxyphenyl)-3-(4-n-octyloxyphenyl)-4,5-dihydroisoxazole

Δ2-Isoxazolines constitute an important class of five-membered heterocycles which have significant synthetic and biological applications. Herein is presented a concise route to the synthesis of liquid crystals based on isoxazolines and structural characterization of 5-[4-(tert-butoxy)phenyl]-3-[4-(n-octyloxy)phenyl]-4,5-di-hydroisoxazole.


Chemical context
Nitrogen-and oxygen-containing heterocycles known as Á 2isoxazolines constitute an important class of five-membered heterocycles which have significant synthetic and biological applications (Pirrung et al., 2002;Choe et al., 2016;Huang et al., 2017;Stosic-Grujicic et al., 2007). Isoxazolines display diverse biological and pharmacological properties. This unique class of pharmacophores occurs naturally in many therapeutic agents. The chlorinated isoxazoline antitumor antibiotics U-42,126 and U-43,795 isolated from Streptomyces sviceus, exhibit significant activity against L 1210 lymphoid leukaemia in mice Hanka et al., 1975). Inspired by this class of natural antibiotics, a new library of natural products probes have been designed, synthesized and tested for bacterial proteome analysis (Orth et al., 2010). Nitrofuranylisoxazolines with increased proteolytic stability have been investigated, leading to the discovery of several compounds with potent in vitro anti-tuberculosis activity (Tangallapally et al., 2007). Trihalomethyl-pyrimidine sugarmodified nucleosides containing the isoxazoline ring were synthesized and their in vitro antiproliferactive activity evaluated against human cancer cell lines and one of them was three times more selective than MXT standard anticancer drugs (Lobo et al., 2015). Isoxazolines have proven be an excellent GABA receptors, as demonstrated by Ozoe et al. (2010) who reported isoxazoline A1443 to exhibit antiparasitic activity against cat fleas and dog ticks comparable to that of the commercial ectoparasiticide fipronil. From a synthetic point of view, Á 2 -isoxazolines constitute an important way to synthesize many natural products with diverse and intricate molecular connectivity. Bafilomycin A1 and erythromycin A, reported by the Carreira group, are examples of the versatility of isoxazoline in the total synthesis of natural products (Kleinbeck & Carreira 2009;Muri & Carreira 2009).

Supramolecular features
In the crystal, molecules of Á 2 -isoxazolines are accommodated in sheets parallel to (010). In each sheet, centrosymmetrically related molecules are connected by a pair of weak non-classical C-HÁ Á ÁO hydrogen bonds (Table 1), forming dimeric units (Fig. 2), which are further linked into chains parallel to the b axis by weak C-HÁ Á ÁO hydrogen bonds involving the oxygen atoms of the t-butoxy group as acceptors. No C-HÁ Á Á contacts orinteractions involving the benzene rings of the 3,5-diarylisoxazoline system are observed.

Database survey
A search of the 3,5-diarylisoxazoline moiety revealed 22 entries in the Cambridge Structural Database (Version 2.0.1, update of February 2019; Groom et al., 2016). However, when the search was restricted to para-diether-3,5-diarylisoxazoline, just one entry was retrieved. The match AWUYUN is associated with the work published by Samshuddin et al. (2011), which describes the crystal structure of 3,5-bis(4-methoxyphenyl)-4,5-dihydroisoxazole. In both cases, the fivemembered isoxazoline ring is coplanar with the phenyl ring bonded to the nitrogen side, whereas the phenyl ring on the oxygen side is very twisted, with dihedral angles between the mean planes of the phenyl rings close to orthogonal.

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq C1  (12)