Some chalcones derived from thiophene-3-carbaldehyde: synthesis and crystal structures

A series of 3-(3-phenylprop-1-ene-3-one-1-yl)thiophene derivatives containing –OH, –OCH3, –OCH2CH3 and –Br at the para-position of the phenyl ring have been synthesized and their molecular and crystal structures are reported.


Chemical context
Chalcones, typically referred to as Michael acceptors, can react with nucleophiles at the electrophilic -position of the unsaturated system (Amslinger, 2010). Many chalcone derivatives containing an ,-unsaturated carbonyl show potential biological applications such as being effective against amyloid -induced cytotoxicity (Bukhari et al., 2014) and irreversibly angiotensin-converting enzyme inhibitors (Hea-Young Park Choo et al., 2000).

Supramolecular features
In chalcone derivative 1, which crystallizes in the orthorhombic space group Pbca, the -OH substituent is involved as donor in intermolecular O16-H16Á Á ÁO9 i [symmetry code: (i) x + 1 2 , y, 3 2 À z] hydrogen bonding, resulting in the formation of chains of molecules running in the a-axis direction (Fig. 5  The moleculare structure of 2 showing 50% displacement ellipsoids.

Figure 5
Partial crystal packing of 1 showing the intermolecular hydrogen-bonding interactions as red dashed lines (see Table 1 for details). Table 3 Hydrogen-bond geometry (Å , ) for 3.
Cg1 and Cg2 are the centroids of the major-and minor-disorder components of the thiophene ring, respectively. symmetry code: (iii) x À 1, y, z]. These intermolecular interactions result in the formation of sheets of molecules parallel to the ac plane (Fig. 7).
No voids orstackings are observed in the crystal packing of 1-4.
In the crystal of 1,3-bis(3-thienyl)prop-2-en-1-one (UNAJIE; Baggio et al., 2016), the stereochemistry about the double bond is E and the dihedral angle between the thiophene rings is 8.88 (10) . Columns of stacking molecules along [010] indicate thatinteractions play an important role in the crystal packing, together with C-HÁ Á ÁO hydrogen bonds between the columns.

Hirshfeld surface analysis
The Hirshfeld surface analysis (Spackman & Jayatilaka, 2009) and the associated two-dimensional fingerprint plots (McKinnon et al., 2007) were performed using CrystalExplorer (Turner et al., 2017). The Hirshfeld surfaces of compounds 1-4 mapped over d norm are given in Fig. 9. The relative distributions from the different interatomic contacts to the Hirshfeld surfaces are presented in Table 5.
The bright-red spots in Fig. 9c Fig. 9d) shows no short interatomic contacts. Again the C-HÁ Á Á interaction with the disordered thiophene ring is reflected in the high contribution from CÁ Á ÁH/HÁ Á ÁC contacts (32.6%) to the Hirshfeld surface (Table 5).
For the four derivatives, the largest contributions of interatomic contacts to the Hirshfeld surface are contacts in which H atoms are involved (Table 5).

Synthesis and crystallization
The reaction scheme to synthesize the title compounds 1-4 is given in Fig. 10.
Synthesis of a,b-unsaturated ketone compounds 1-4: In a 250 mL beaker, thiophene-3-carbaldehyde (0.1 mole) and substituted acetophenone (0.1 mol) were dissolved in ethanol (100 mL). To this mixture, a 50% KOH (10 mL) solution was added and the mixture was stirred by a magnetic stirrer for 5 h at room temperature until a precipitate appeared. The products 1-4 were obtained as solids, which were filtered under low pressure and recrystallized from ethanol.

Figure 10
Reaction scheme for the title compounds 1-4.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 6.
All H atoms were placed in idealized positions and refined in riding mode, with U iso (H) values assigned as 1.2U eq of the parent atoms (1.5 times for methyl groups), with C-H distances of 0.93 (aromatic and CH), 0.96 (CH 3 ) and 0.97 Å (CH 2 ), and O-H distances of 0.82 Å (rotating OH).

1-(4-Hydroxyphenyl)-3-(thiophen-3-yl)prop-1-en-3-one (1)
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.

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.

1-(4-Ethoxyphenyl)-3-(thiophen-3-yl)prop-1-en-3-one (3)
Crystal data  (17) 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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq S1 0.28921 (3) 0.41932 (9) 0.57261 (6)   where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.40 e Å −3 Δρ min = −0.46 e Å −3 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.  (2) Geometric parameters (Å, º)