Crystal structure, Hirshfeld surface analysis and computational study of a rhodamine B–salicylaldehyde Schiff base derivative

The molecular structure of the title compound comprises two parts, xanthene and isoindole, sharing a central quaternary carbon atom. Both the xanthene and isoindole moieties are nearly planar and are almost perpendicular.


Chemical context
Rhodamine B derivatives are employed extensively as molecular probes in the study of complex biological systems because of their high absorption coefficients, high fluorescence quantum yields and long-wavelength absorptions and emissions (Bao et al., 2013;Biswal & Bag, 2013). On the basis of the spirolactam/ring-opened amide equilibrium of rhodamine, several fluorescence-based sensing systems for metal ions have been developed. Most of the reported sensors based on rhodamine B derivatives are fluorescent chemosensors for metal ion detection (Quang & Kim, 2010;Kim et al., 2008;Kwon et al., 2005;Liu et al., 2013;Ni et al., 2013). A rhodamine ISSN 2056-9890 B derivative is usually used as a chemosensor because of its good photophysical properties, sensitivity, the low cost of chemical reagents and the ease of modifying its structure. Rhodamine B derivatives have naked-eye detection and show off-on fluorescent property when reacting with metal ions. Fig. 1 shows the molecular structure of the title compound (rhodamine B -salicylaldehyde derivative, RbSa) together with the atomic labelling scheme. The title compound crystallizes in the monoclinic space group P2 1 /c, and the asymmetric unit contains a single molecule in a general position. The molecule can be seen as having two distinct parts sharing a central quaternary carbon atom. The atoms in the xanthene moiety, namely C5-C10, O1, C11-C17, are almost coplanar, as seen from the r.m.s. deviation of 0.0411 Å (Fig. 2a). The atoms C11, C22-C28, O2, N3 and N4 of the isoindole unit are also nearly coplanar with an r.m.s. deviation of 0.0545 Å (Fig. 2b). These two planes are almost perpendicular to each other, the dihedral angle between their mean planes being 87.71 (2) (Fig. 2c). The four ethyl groups present in the molecule point out of the xanthene plane and are on the same side of the plane; the corresponding out-of-plane torsion angles C16-N2-C19-C18, C16-N2-C21-C20, C5-N1-C2-C1 and C5-N1-C4-C3 are 73.76 (15), À79.52 (15), À86.26 (15) and 65.09 (16) , respectively.

Structural commentary
The major tautomer of the rhodamine B -salicylaldehyde Schiff-base derivative is usually the enol form for compounds having hydroxy and azamethylene groups attached to the benzene ring in the ortho positions Wattanathana et al., 2012Wattanathana et al., , 2016. Similarly, our title compound appears to be in its enol form. The corresponding H atom was located and freely refined at a distance of 1.02 (3) Å from the O atom and 1.72 (2) Å from the N atom (Table 1, Fig. 3). The strong intramolecular O-HÁ Á ÁN hydrogen bond bridging the hydroxyl group and its neighbouring nitrogen atom forms an S(6) graph-set motif involving atoms N4, H3, O3, C35, C30    The molecular structure of RbSa, showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. The non-IUPAC atom labelling is for the convenience of discussion.

Figure 3
A view of molecule illustrating the S(6) ring of the intramolecular hydrogen bond constructed from the N4-C29-C30-C35-O3-H3 synthon. and C29 and stabilizes a rigid configuration that can partially inhibit the rotation of the phenyl ring about the N-N bond.

Figure 4
The unit cell and molecular packing in the title compound with the unitcell contents projecting down the [100] direction. The orange dots represent inversion centres and the green and magenta lines represent glide planes and twofold axes, respectively.

Figure 5
A view of the crystal packing showing C-HÁ Á Á interactions between C18-H18A and the C22-C27 ring of the isoindole unit.  Adhikesavalu et al., 2001) and cyclic lactones (IV) (FUFTIJ; Kvick et al., 2000). In our case, the carboxylic acid functional group is sequentially transformed into a cyclic lactam with a hydrazone side chain. The counter-anions are the other key factor in the crystal structures of rhodamine B derivatives. Mizuguchi (2008)

Synthesis and crystallization
The reagents were purchased from commercial suppliers and used without further purification: rhodamine B (Fluka Chemicals), hydrazine hydrate (Across Organics), salicyaldehyde (Sigma-Aldrich), hydrochloric acid (Valchem), ammonium hydroxide (Mallinckrodt Chemicals) and sodium hydroxide (RCI Labscan). Solvents including absolute ethanol (EtOH), methanol (MeOH) and chloroform were purchased from RCI Labscan and Merck. 1 H NMR spectra were measured on a Varian INOVA 400 spectrometer at 400 MHz in CDCl 3 . The FTIR spectrum was obtained using a Bruker Tensor 27 spectrometer, while the mass spectrum was recorded on a Bruker microTOF-Q III. The melting point of the obtained sample was measured by a Stuart Scientific melting-point analyser (SMP10). Fig. 8 shows the chemical structures of the starting materials and intermediate and the synthetic route of the rhodamine-Schiff-base derivative studied in this work (RbSa). Firstly, the RbH intermediate compound was synthesized from the reaction between rhodamine B and hydrazine hydrate. Rhodamine B (1.20 g, 2.50 mmol) was dissolved in ethanol. An equimolar amount of hydrazine hydrate (2.0 ml, 2.5 mmol) was added to this solution. The mixture was then refluxed at 373 K under N 2 for 2 h. During the reaction, the colour of the solution changed from dark purple to light orange. After the reaction was complete, a precipitate of RbH was obtained by solvent evaporation, and then 1 M HCl was added to re-dissolve the crude product to obtain a clear red solution. After that, 1 M NaOH was added slowly in order to precipitate the purer RbH compound out. The obtained RbH was filtered under reduced pressure. The title compound RbSa was then prepared from the reaction of the filtered RbH (0.48 g, 0.97 mmol) and salicylaldehyde (0.12 ml, 1 mmol) in ethanolic solution. A pink precipitate of RbSa formed after reflux at 353 K for 12 h under an N 2 atmosphere. The RbSa precipitate was separated by vacuum filtration and washed three times with cold ethanol. After recrystallization from chloroform and methanol mixed solvents with a volume ratio of 1:1, light-violet single crystals were obtained after several days, m.p. 495 K. HR

Computational details
All reported calculations (geometry optimizations, vibrational frequencies, and relative energies) were performed using Gaussian09 (Frisch et al., 2009) using density functional theory (DFT) at the CAM-B3LYP/6-31 G(d) level. The ground-state geometries of the RbSa molecules with different conformers were optimized, and vibrational frequency calculations were performed to confirm that the optimized structures correspond well to a local minimum or a transition state. The hybrid exchange-correlation functional CAM-B3LYP was selected because it has been found to be a method of choice in important reported studies (Klinhom et  The synthetic route and the structures of RbSa. tional time and the accuracy of the results. All calculations were carried out in ethanol using a conductor-like polarizable continuum model (CPCM) (Scalmani et al., 2006).

Quantum chemical calculations
For a more in-depth insight into the molecular structures of RbSa, density functional theory (DFT) calculations at the CAM-B3LYP/6-311 G(d,p) level were carried out. They were mainly applied to investigate the intramolecular protontransfer reaction during the enol-keto tautomerization mechanism. The molecular structures of two essential conformers (the enol and keto forms) of the title compound were first obtained by geometry optimizations without any constraints. Starting from the enol form and going to the keto form, the potential energy curve (PEC) was explored by elongating the O-H bond in steps of 0.1 Å (from 1.0 to 1.8 Å ). The CAM-B3LYP optimized conformers and their relative energies are depicted in Fig. 9.
The enol form is the most stable conformer (O-H = 0.98 Å ) with the lowest relative energy, and the keto form (O-H = 1.76 Å ) is found to be slightly higher in energy than the enol form by 9.1 kcal mol À1 . All along the tautomerization path, the six atoms involved in the initial S(6) graph-set motif remain coplanar, but a rotation occurs around the N-N bond between the diaminoxanthene and the salicylidene aniline moieties, which move from being coplanar in the enol form to being nearly perpendicular in the keto-form (Fig. 9). The rotation of the N-N bond gives rise to the elongation and then the breakage of the O-H bond in the enol form, resulting in the formation of the N-H bond (keto form). Although the enol-keto tautomerization involves breakage of the O-H bond, the intramolecular hydrogen-bonded S(6) ring still remains even in the keto form, involving the same atoms in the synthon as in the enol form. According to the relative energy calculations, it can be concluded that the phenolic -OH group can form a stronger intramolecular hydrogen-bonding interaction (enol form) with the N atom of the diaminoxanthene moiety than with the -NH group of the phenolate O in the keto closed form. The result is in a good agreement with the X-ray crystal structure in that the enol form is the dominant conformer.
Based on the highest energy structure obtained on the PEC, we optimized the molecular geometry of the transition state of the keto-enol tautomerization pathway without constraints. The single negative (imaginary) vibrational frequency calculated for the obtained structure showed that the transition state was correctly determined. The transition state lies 10.4 kcal mol À1 higher in energy than the enol form and only 1.3 kcal mol À1 above that of the keto form (Fig. 9). The optimized structure reveals an O-H distance of 1.30 Å , in between the O-H distances observed in the enol and keto conformers, but closer to that of the enol-conformer. The energy curve is rather flat between the transition state and the keto form, despite a difference of about 0.5 Å between the O-H distances (1.30 and 1.76 Å , respectively). Besides the fact that the enol form exhibits the lowest absolute energy and is the most stable conformer, that flatness also explains why the keto form is not as stable and can easily return to the enol form in solution under normal conditions.

Figure 9
Optimized structures and relative energies of the enol form, the keto form and the transition state formed during the tautomerization process of the compound RbSa, calculated in ethanol at the CAM-B3LYP level using a 6-311 G(d,p) basis set.

3′,6′-Bis(diethylamino)-2-[(2-hydroxybenzylidene)amino]spiro[isoindoline-1,9′-xanthen]-3-one
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.