Crystal structure of racemic (R/S,E)-2-(4-hydroxyphenyl)-4-(2-phenylhydrazin-1-ylidene)chromane-5,7-diol ethanol monosolvate

The structure of racemic (R/S,E)-2-(4-hydroxyphenyl)-4-(2-phenylhydrazin-1-ylidene)chromane-5,7-diol ethanol monosolvate, has been determined. The packing is assisted by C—H⋯O, O—H⋯O, O—H⋯N and O—H⋯C(π) type hydrogen bonds, and the pyran ring has an envelope pucker.


Chemical context
Naringenin is a naturally occurring flavanone compound found in citrus fruits, bergamot and tomatoes (Cai et al., 2004). It has been reported to have a wide range of biological activities, including anti-viral, anti-inflammatory and antiaging properties (Heim et al., 2002). Due to its inherent medicinal properties, derivatives of naringenin have also been synthesized and studied as potential treatments for disease. The title compound, (R/S,E)-2-(4-hydroxyphenyl)-4-(2phenylhydrazineylidene)chromane-5,7-diol, is a hydrazone naringenin derivative that has been reported to induce apoptosis in human cervical cancer cells (Kim et al., 2012). Its close structural analog, 5-hydroxy-7,4 0 -diacetyloxyflavanone-N-phenylhydrazone, exhibits cytotoxicity against non-smallcell lung cancer cells (Bak et al., 2011). Despite their biological value, crystal structures have not been reported to date of any hydrazone derivatives of naringenin. Herein, we report the first crystal structure of a hydrazone derivative of naringenin.

Structural commentary
The title compound along with the solvent (ethanol) molecule in 1:1 ratio, yielded a disordered mixed enantiomeric crystal in a centrosymmetric lattice (P1, Fig. 1). The structure was solved and refined in P1 and a distorted structure was found. The asymmetric unit has two racemates occupying the same position in a ratio of 0.562 (6):0.438 (6). Enantiomeric structures in centrosymmetric lattices have been discussed by Flack (2003). The title molecule has three phenyl rings, one of which is fused with a pyran ring. The molecule in the asymmetric unit is a superposition of the two enantiomers in the ratio of 0.562 (6):0.438 (6). The phenylhydrazone group is nearly coplanar with the chromane ring system [dihedral angle = 15.5 (1) ], while the the 4-hydroxyphenyl ring is perpendicular [dihedral angle = 87.2 (1) ] to the chromane. The pyran ring has an envelope pucker [Q = 0.363 (3) Å , = 57.6 (3) ; and for the enantiomer: Q = 0.364 (3) Å , = 127.4 (4) ]. An intramolecular O-HÁ Á ÁN hydrogen bond exists between one of the hydroxy groups on the chromane ring and the nitrogen of the hydrazone group (Table 1). The carbon-nitrogen double bond [N1 C7 = 1.295 (2) Å ] exists as the E isomer.

Supramolecular features
In the crystal, O-HÁ Á ÁC() type hydrogen-bond interactions between the solvent ethanol and phenyl ring are observed (Table 1, Fig. 2). The phenyl ring is expected to have a partial negative charge because of the two nitrogen atoms (known electron-releasing groups) just before the phenyl ring (Stewart, 1985 Symmetry codes: (i) Àx þ 1; Ày þ 1; Àz þ 1; (ii) Àx þ 1; Ày þ 2; Àz þ 2; (iii) x; y þ 1; z þ 1.   Displacement ellipsoid drawing at 50% probability level of the asymmetric unit showing the superposition of two enantiomers in the asymmetric unit. The disorder in the solvent (ethanol) molecule is resolved here, shown in two partial-occupancy locations.

Database survey
A structure search was performed in Scifinder and Reaxys. A text search ('flavanone' and 'chroman-4-ylidene' and 'dihydrochromen-4-phenylhydrazone') was performed in the Cambridge Structural Database (Groom et al., 2016;accessed January 2022). To date, no crystal structures have been reported for a hydrazone derivative of naringenin, including the two flavanones mentioned in the Chemical context section. The most similar structures for which crystal data have been reported include acyl hydrazone derivatives of 2-phenylchroman-4-one and hesperetin. In particular, crystal structures for 2 0 -[2-(4-fluorophenyl)chroman-4-ylidene]isonicotinohydrazide (Nie et al., 2006) and

Synthesis and crystallization
The title compound was synthesized according to a previously reported procedure (Bak et al., 2011).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The superposition of two enantiomers in the asymmetric unit, and the disorder in the solvent (ethanol molecule) necessitated 183 constraints. The hydrogen atoms were placed in their geometrically calculated positions and their coordinates refined using the riding model with parent-atom-H lengths of 0.93 Å (CH), 0.98 Å (chiral-CH), 0.96 Å (CH 3 ), 0.97 Å (CH 2 ), 0.86 Å (NH) or 0.82 Å (OH). Isotropic displacement parameters for these atoms were set to 1.2 (CH, NH) or 1.5 (CH 3 , OH) times U eq of the parent atom. Idealized Me of the ethanol molecule were refined as rotating group(s): C22A and C22B (H22A through F) and its idealized tetrahedral OH refined as a rotating group: O5A and O5B (H5A, H5B).