Crystal structure of 4-[(2-hydroxy-3-methoxybenzyl)amino]benzoic acid hemihydrate

In the crystal, the system of O—H⋯O hydrogen bonds, including bridging water molecules residing on crystallographic twofold axes, results in a two-dimensional layered structure. Within the layers, there are also weak N—H⋯π interactions involving the vanilline benzene ring.


Chemical context
The title compound is obtained by reduction of reported (Kamaal et al., 2018) (E)-4-(2-hydroxy-3-methoxybenzylideneamino)benzoic acid with sodiumborohydride. The Schiff base is formed by condensation of 4-aminobenzoic acid with o-vanilline. Both p-aminobenzoic acid and o-vanilline have biological importance, for example as a bacterial cofactor involved in the synthesis of folic acid (Robinson, 1966). Another example is benzocaine, the ethyl ester of p-aminobenzoic acid, which is a local anaesthetic. The mechanism includes inhibiting voltage-dependent sodium channels on the nerve membrane, which results in stopping the signal propagation (Neumcke et al., 1981). The present work is also a part of an ongoing structural study of Schiff bases and secondary amines for their utilization in the synthesis of new organic compounds and application of excited-state proton transfer and fluorescent chemosensor (Faizi et al., 2016a(Faizi et al., ,b, 2018aKumar et al., 2018;Mukherjee et al., 2018).

Structural commentary
The molecular structure of the title compound is illustrated in Fig. 1. The title compound has two substituted aromatic rings ISSN 2056-9890 at either end of the -CH 2 -NH-linkage [C aryl -CH 2 -NH-C aryl torsion angle = À83.9 (2) ]. The water solvent stabilizes the crystal structure through hydrogen bonding. The secondary amine N atom has a practically planar trigonal configuration deviating by just 0.03 (1) Å from the mean plane of the adjacent atoms, and it is apparently conjugated with the adjacent benzene ring [the C-N bond length is 1.368 (2) Å ]. For comparison, the reported C-N distance in crystal structure of the ethyl 4-[(E)-(4-hydroxy-3-methoxybenzylidene)amino]benzoate Schiff base is 1.274 (2) Å (Ling et al., 2016) and in the zwitterion it is 1.312 Å (Kamaal et al., 2018). The C6-O2 bond of the hydroxyl group [1.371 (2)Å ] and those of the acid moiety [O3-C15 = 1.224 (2) and O4-C15 = 1.317 (2) Å ] are in the expected ranges. The C5-O1 bond length to the methoxy group is 1.372 (2) Å .

Supramolecular features
In the crystal, molecules are connected via O-HÁ Á ÁO interactions forming layers in the ab plane (   The molecular structure of the title compound, showing the atom labelling. The intermolecular O-HÁ Á ÁO hydrogen bond involving the water molecule is shown as a dashed line (see Table 1 for details). Displacement ellipsoids are drawn at the 40% probability level.

Figure 3
A view along the c axis of the zigzag chain in the crystal of the title compound. The N-HÁ Á Á interactions are shown as dashed lines (see Table 1 for details). Table 1 Hydrogen-bond geometry (Å , ).
Cg1 is the centroid of the C2-C7 ring.  (Salman et al., 2017), in which the 3-methoxy group in the title compound is replaced by a hydrogen atom and the carboxylic acid is replaced by an ester. The torsion angle C aryl -CH 2 -NH-C aryl in the title compound [À83.9 (2) ] compares well to those in I (73.68 ), II (77.38 ) and IV (À87.28 ) despite the difference in substituent groups.

Synthesis and crystallization
To a hot stirred solution of 4-aminobenzoic acid (PABA) (1.00 g, 7.2 mmol) in methanol (15 ml) was added vanillin (1.11 g, 7.2 mmol). The resultant mixture was then heated under reflux. After an hour, precipitates were formed. The reaction mixture was heated for about a further 30 minutes for the completion of the reaction, which was monitored through TLC. The reaction mixture was cooled to room temperature, filtered and washed with hot methanol. It was then dried in a vacuum to give (E)-4-(2-hydroxy-3-methoxybenzylideneamino)benzoic acid (1) in 78% yield. Compound (1) (1.00 g, 3.7 mmol) was dissolved in 25 mL of methanol and reduced by addition of excess sodium borohydride (0.28 g, 7.4 mmol). The solution was stirred until the yellow colour disappeared. Then the solution was diluted with 8-10 times the volume of water and the pH was adjusted to 6 by addition of 12% HCl. The white precipitate was collected and dried in air. Colourless single crystals of the title compound, suitable for X-ray analysis, were obtained by slow evaporation of a methanol solution.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The N-H and O-H H atoms were located in difference-Fourier maps and freely refined, while the C-bound H atoms were included in calculated positions and treated as riding, with fixed C-H = 0.93 Å , and U iso (H) = 1.2U eq (C,N).  program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

4-[(2-Hydroxy-3-methoxybenzyl)amino]benzoic acid hemihydrate
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.