Syntheses and crystal structures of benzyl N′-[(E)-2-hydroxybenzylidene]hydrazinecarboxylate and benzyl N′-[(E)-5-bromo-2-hydroxybenzylidene]hydrazinecarboxylate

The syntheses and low-temperature (90 K) crystal structures of benzyl N′-[(E)-2-hydroxybenzylidene]hydrazinecarboxylate and benzyl N′-[(E)-5-bromo-2-hydroxybenzylidene]hydrazinecarboxylate are presented.


Chemical context
Hydroxybenzylidene hydrazines exhibit a wide spectrum of biological activities (Sersen et al., 2017). Benzaldehydehydrazone derivatives have received considerable attention for several decades as a result of their pharmacological activity (Parashar et al., 1988) and photochromic properties (Hadjoudis et al., 1987). Benzaldehydehydrazone derivatives are also important intermediates in the synthesis of 1,3,4oxadiazoles, which are versatile compounds with many useful properties (Borg et al., 1999). Synthesis and biological activities of new hydrazide derivatives (Ö zdemir et al., 2009) and biological activities of hydrazone derivatives (Rollas & Kü çü kgü zel, 2007) have been reported. In view of the importance of benzylidene hydrazines and benzaldehydehydrazone derivatives in general, this paper reports the crystal structures of the title compounds, C 15 H 14 N 2 O 3 (I), and C 15 H 13 BrN 2 O 3 (II).

Structural commentary
The molecular structures of benzyl N 0 -[(E)-2-hydroxybenzylidene]hydrazinecarboxylate (I) (Fig. 1) and benzyl N 0 -[(E)-5-bromo-2-hydroxybenzylidene]hydrazinecarboxylate (II) (Fig. 2) each consist of a central N 0 -methylidenemethoxycarboxyl core flanked by a benzyl group attached to the singly bonded oxygen and a 2-hydroxyphenyl (I) or 5-bromo-2-hydroxyphenyl (II) attached to the methylidene. There are no unusual bond lengths or angles in either structure. The molecules have strong intramolecular O-HÁ Á ÁN hydrogen bonds (Tables 1 and 2), forming S(6) ring motifs (Etter et al., 1990). The asymmetric unit of I contains a single molecule while that of II contains two (labelled A and B in Fig. 2). In each case, the [(hydroxyphenyl)methylidene]carbohydrazide moieties are essentially planar [r.m.s. deviations 0.0429 Å (I), 0.0905 Å (IIA), 0.0692 (IIB)]. These form dihedral angles of 79.92 (3) , 79.74 (4) , and 74.27 (4) to the benzyl groups of I, IIA, and IIB, respectively. Indeed, the V-shaped conformations of IIA, and IIB are strikingly similar, with I only deviating to any appreciable degree at the benzyl group, as evidenced by an overlay of the three molecules (Fig. 3). The conformation of I differs from IIA and IIB primarily by the torsion angles about bonds O2-C9 and C9-C10 (Table 3).

Supramolecular features
In addition to the strong O-HÁ Á ÁN intramolecular hydrogen bonds in I and II, the structures both feature strong N-HÁ Á ÁO and weaker C-HÁ Á ÁO intermolecular hydrogen bonds. These interactions are summarized in Tables 1 and 2. The packing modes are, however, quite different.

Figure 3
A least-squares fit overlay of I, IIA, and IIB showing the similarity of their conformations. That of I (blue) differs primarily in the orientation of the benzyl group (right). Diagram generated using Mercury (Macrae et al., 2020).
In II, the independent molecules (A and B) make hydrogen bonds to 2 1 -screw-related copies of themselves via strong (N2-H2NÁ Á ÁO1) and weak (C3-H3Á Á ÁO2 and C6-H6Á Á ÁO3) hydrogen bonds (Table 2), forming R 2 2 (8) and R 3 3 (13) ring motifs (Etter et al., 1990), leading to adjacent pairs of ribbons that extend along [010] (Fig. 6). The 5-bromo-2hydroxyphenyl and benzyl groups of IIA and IIB have notably different environments. For example, inversion-related (Àx, Ày, Àz) pairs of IIA molecules have close contacts of 3.3379 (9) Å between their Br1A atoms and the centroid of the inversion-related C10A-C15A ring. There is no corresponding close contact for the IIB molecule (Fig. 7  V-shaped molecules of I stack into columns parallel to the a-axis direction.

Figure 5
A partial packing plot of I showing hydrogen bonding as dashed lines. N-HÁ Á ÁO and a pair of C-HÁ Á ÁO (bifurcated) hydrogen bonds link nglide-related molecules into layers parallel to ac.   In spite of their similar conformations, inversion-related pairs of IIA molecules (upper) are different from inversion-related pairs of IIB molecules (lower). For IIA there are close contacts between bromine and the inversion-related benzene ring, as shown by the dotted line. No such interaction exists for IIB.
The differences in packing are also apparent in the atomatom contact coverages, as quantified by CrystalExplorer

Database survey
A search of the Cambridge Structure Database (CSD, v5.43 with updates as of June 2022; Groom et al., 2016) for a search fragment consisting of the structure of I, but with the two aromatic rings replaced by 'any group' gave 340 hits. A fragment including the benzyl group attached to the equivalent of O2 in I/II gave 105 hits, while a fragment including a phenyl ring at C7 gave 37 hits. A fragment consisting of I but without the phenolic OH group gave just four hits: HIXQIQ (Dong & Wang, 2014), QAVFAY (Shen et al., 2022), GEZTUD (Chang et al., 2018) and PIVKUD (Zhang et al., 2019). In HIXQIQ, a 5-chloro-2-hydroxy-2-(methoxycarbonyl)-2,3-dihydro-1H-inden-1-ylidene) group is attached to the hydrazine. QAVFAY features a four-membered 1,2-diazete ring, with the phenyl group fluorinated at its 4-position. Structures GEZTUD and PIVKUD each feature pyrazole rings; the former having a 2,2,2-trifluoroethyl group attached to the pyrazole and a methyl at the 4-position of the phenyl ring, and the latter having a 3,4,5-trimethoxyphenyl attached to its pyrazole ring.

Figure 9
Fingerprint plots obtained from a Hirshfeld surface analysis for II using CrystalExplorer, separated into (a) HÁ Á ÁH (33.8% coverage), All other contacts are negligible.

Synthesis and crystallization
Preparation of I and II followed similar synthetic routes. Either 2-hydroxybenzaldehyde (1.2 g, 0.01 mol) (for I) or 5bromo-2-hydroxybenzaldehyde (2.0 g, 0.01 mol) (for II) and benzyl carbazate (1.66 g, 0.01 mol) were dissolved in methanol (25 ml) and stirred for 3 h at room temperature. The resulting solids were filtered off and recrystallized from ethanol to give I and II with yields of 80% in both cases. The general reaction scheme is summarized in Fig. 10. Single crystals suitable for X-ray analysis for both I and II were obtained by slow evaporation of methanolic solutions at room temperature (m.p.: 400-402 K for I and 468-470 K for II).

Crystal handling, data collection, and refinement
Crystals of I and II were each secured on the tips of fine glass fibres held in copper mounting pins. The crystal of I was mounted from a shallow liquid-nitrogen dewar using tongs first developed for protein cryocrystallography (Parkin & Hope, 1998), while the crystal of II was mounted directly into a cold-nitrogen stream. Data for both samples (Cu K for I and Mo K for II) were collected with the crystals held at 90.0 (2) K. Determination of the absolute structure for I was inconclusive via traditional full-matrix refinement of Flack's parameter [x = À0.08 ( (10); Parsons et al., 2013] give credence to the assignment. Refinement progress was checked using PLATON (Spek, 2020) and by an R-tensor (Parkin, 2000). Crystal data, data collection, and refinement statistics are summarized in Table 5

Benzyl N′-[(E)-5-bromo-2-hydroxybenzylidene]hydrazinecarboxylate (II)
Crystal data Special details Experimental. The crystal was mounted using polyisobutene oil on the tip of a fine glass fibre, which was fastened in a copper mounting pin with electrical solder. It was placed directly into the cold gas stream of a liquid-nitrogen based cryostat (Parkin & Hope, 1998). Diffraction data were collected with the crystal at 90K, which is standard practice in this laboratory for the majority of flash-cooled crystals. 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.