Crystal structure of the co-crystal butylparaben–isonicotinamide (1/1)

The title 1:1 co-crystal, butylparaben–isonicotinamide [BPIN, butyl 4-hydroxybenzoate isonicotinamide (1/1)], crystallizes with one molecule each of butylparaben and isonicotinamide. In the crystal, various BPN and ISN molecules are linked via O—H⋯N, N—H⋯O and N—H⋯O=C hydrogen bonds, creating a layered structure.


Chemical context
Butylparaben (butyl 4-hydroxybenzoate, BPN), a naturally derived preservative, is widely used in pharmaceutical products and cosmetics (Charnock & Finsrud, 2007), and generally considered to be safe (Hossaini et al., 2000). The solubility of BPN has been reported in various solvents (Yang & Rasmuson, 2010;2013). Isonicotinamide (ISN) is a widely used coformer (Aakerö y et al., 2003) and is known to form hydrogen-bonded co-crystals with phenolic compounds (Vishweshwar et al., 2003;McKellar et al., 2014). The sample of butyl paraben-isonicotinamide (BPIN) co-crystals was isolated during an experimental co-crystal screening of BPN. The sample was identified as a novel form using multi-sample foil transmission X-ray powder diffraction analysis (Florence et al., 2003). A suitable sample for single crystal X-ray diffraction analysis was obtained from slow evaporation of 1:1 molar solution of BPN with ISN in ethanol at room temperature.

Structural commentary
The title co-crystal crystallizes with one molecule of BPN and a molecule of ISN in the asymmetric unit (Fig. 1). In the solid state, the BPN molecule exhibits a planar conformation with a fully extended trans zigzag butyl ester group.

Supramolecular features
The crystal structure is defined by hydrogen-bonded BPN-ISN-ISN-BPN dimers of paired BPNÁ Á ÁISN molecules connected via O-HÁ Á ÁN hydrogen bonds (Fig. 2a). These BPN-ISN-ISN-BPN dimers are further connected to each other via N-HÁ Á ÁO C hydrogen-bonds extending the structure to form ribbons in [011]; see Fig. 2b and Table 1. These ribbons further stack along a axis to produce a layered structure (Fig. 3) which is stabilized by various van der Waals interactions and exhibits short CÁ Á ÁC contacts of 3.285 (3) Å . PIXEL (Gavezzotti, 2002;2003) calculations revealed that the largest contribution to crystal stabilization comes from the dispersion energy (E d , À98.5 kJ mol À1 ). The next greatest contribution comes from electrostatic (Coulombic) energy, (E C , À67.3 kJ mol À1 ) and then from polarization energy (E p , À32.2 kJ mol À1 ).

Database survey
The crystal structures of BPN (CSD refcode: UDOMIL) (Yang & Rasmuson, 2013) and its clathrate hydrate (CSD refcode: VOFKIL) have been reported in the literature (de Vries & Caira, 2008). In UDOMIL, the BPN molecule exhibits a planar conformation except for the terminal ethyl moiety of butyl ester group which is in a cis orientation with respect to the ester group.

Figure 2
Hydrogen bonds in the title compound: (a) hydrogen-bonded (thin grey lines) dimer of paired BPNÁ Á ÁISN molecules; (b) hydrogen-bonded (thin orange lines) ribbon of dimers extended in [011]. Atom colour code: C, N, O and H are grey, blue, red and white, respectively. Hydrogen atoms not involved in hydrogen bonding have been omitted for clarity.

Figure 1
A view of the molecular structure of the asymmetric unit of the title cocrystal, showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The N and O bound H atoms were located in a difference Fourier map and isotropically refined.
The C-bound H atoms were placed in calculated positions and refined as riding atoms: C-H = 0.95-0.99 Å with U iso (H) = 1.5U eq (C) for methyl H atoms and = 1.2U eq (C) for other H atoms.

Figure 3
A portion of the crystal packing showing the layered structure of the title co-crystal. H atoms have been omitted for clarity.  Computer programs: APEX2 and SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL2014 (Sheldrick, 2015),