Crystal structures of (5RS)-(Z)-4-[5-(furan-2-yl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl]-4-oxobut-2-enoic acid and (5RS)-(Z)-4-[5-(furan-2-yl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl]-4-oxobut-2-enoic acid

Stereochemical peculiarities of (5RS)-(Z)-4-[5-(furan-2-yl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl]-4-oxobut-2-enoic acid and (5RS)-(Z)-4-[5-(furan-2-yl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl]-4-oxobut-2-enoic acid, studied by X-ray structural analysis, render impossible their transformation into 3b,6-epoxypyrazolo[5,1-a]isoindoles by a thermal intramolecular Diels–Alder reaction of furan (the IMDAF reaction).


Chemical context
3-(2-Furyl)pyrazolines and their N-acyl derivatives are well known to possess high and diverse biological activity, for example, topoisomerase I and II inhibitory and antiproliferative activity (Ahmad et al., 2016), 5-reductase inhibitory activity (Banday et al., 2014), antibacterial (Joshi et al., 2016;Bhoot et al., 2012), antituberculous (Manna & Agrawal, 2010), anti-inflammatory (Shoman et al., 2009), antifungal activity (Deng et al. 2012), and many others. Pyrazolines, fused with other heterocycles, are much less studied. Thus, the main goal of this work was the synthesis of maleic amides (I) and (II) from (E)-1-(furan-2-yl)-3-arylprop-2-en-1ones ( Fig. 1) with subsequent their transformation into 3b,6epoxypyrazolo[5,1-a]isoindoles by a thermal intramolecular Diels-Alder reaction of furan (the IMDAF reaction). However, we were unable to realize the final stage of the ISSN 2056-9890 purposed synthesis -the thermal IMDAF reaction of maleic amides (I) and (II) (Fig. 2). Unexpectedly, these compounds remained unchanged at temperatures up to 413 K. In order to explain this fact by an understanding of their stereochemical features, an X-ray diffraction study of compounds (I) and (II) was undertaken.  (II)] are practically coplanar with its basal plane [the corresponding dihedral angles are 6.14 (9) and 2.22 (11) in (I) and 6.27 (12) and 3.91 (11) in (II)]. Importantly, the furyl ring plane is twisted relative to the basal plane of the dihydropyrazole ring by 85.51 (8) and 88.30 (7) in (I) and (II), respectively. Apparently, it is such a perpendicular arrangement of the furyl and oxobutenoic acid fragments that inhibits the IMDAF reaction between them. The purposed thermal IMDAF reaction of maleic amides (I) and (II).

Figure 3
The molecular structure of (I). Displacement ellipsoids are shown at the 50% probability level. H atoms are presented as small spheres of arbitrary radius. The dashed line indicates the intramolecular O-HÁ Á ÁO hydrogen bond.

Figure 4
The molecular structure of (II). Displacement ellipsoids are shown at the 50% probability level. H atoms are presented as small spheres of arbitrary radius. The dashed line indicates the intramolecular O-HÁ Á ÁO hydrogen bond.
The nitrogen atom N1 has a planar-trigonal geometry, the sum of the bond angles being 359.9 for (I) and 360.0 for (II). The bond lengths and angles in (I) and (II) are in good agreement with those observed in related structures (Suponitsky et al., 2002;Guo, 2007;Vinutha et al., 2013). The molecules possess an asymmetric center at the C5 carbon atom. The crystals of (I) and (II) are racemic and consist of (5RS)enantiomeric pairs.

Supramolecular features
Although the similarity of the molecular geometries and intramolecular interactions might lead to similar packing motifs, this is not found in the case for (I) and (II). The intermolecular interactions, namely C-HÁ Á ÁO and C-HÁ Á ÁS hydrogen bonding, combined in a different way, give rise to different packing networks.
General procedure. A solution of the corresponding (E)-1-(furan-2-yl)-3-arylprop-2-en-1-one (0.025 mol) in alcohol (15 mL) was added to a solution of hydrazine hydrate (2.5 mL, 0.05 mol) in alcohol (15 mL). The mixture was heated at reflux for 3-5 h (TLC monitoring), then the solvent and the excess of hydrazine hydrate were removed under reduced pressure. The residue, viscous brown oil, was dissolved in benzene (15 mL) and acylated (stirring at room temperature for 1 day) with a solution of maleic anhydride (2.45 g, 0.025 mol) in benzene (25 mL). The precipitated crystals were filtered off and recrystallized from an EtOH-DMF mixture to give the analytically pure maleic amides (I) and (II).   The crystal structure of (II) along the a axis. Dashed lines indicate the intramolecular O-HÁ Á ÁO and intermolecular C-HÁ Á ÁS and C-HÁ Á ÁO hydrogen bonds. Table 1 Hydrogen-bond geometry (Å , ) for (I). Symmetry code: (i) x; y; z À 1.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. X-ray diffraction studies were carried out on the 'Belok' beamline ( = 0.96990 Å ) of the National Research Center "Kurchatov Institute" (Moscow, Russian Federation) using a MAR CCD detector. For each compound a total of 360 images were collected using an oscillation range of 1.0 (' scan mode, two different crystal orientations) and corrected for absorption using the SCALA program (Evans, 2006). The data were indexed, integrated and scaled using the utility iMOSFLM in CCP4 (Battye et al., 2011).
The hydrogen atoms of the hydroxyl groups were localized in difference-Fourier maps and refined in an isotropic approximation with fixed displacement parameters [U iso (H) = 1.5U eq (O)]. The other hydrogen atoms were placed in calculated positions with C-H = 0.95-1.00 Å and refined using a riding model with fixed isotropic displacement parameters [U iso (H) = 1.2U eq (C)].
The insufficient data completeness of 96.7% in the case of (I) is determined by the low (triclinic) crystal symmetry. It is very difficult to get good data completeness at this symmetry using the ' scan mode only ('Belok' beamline limitation), even though we have run two different crystal orientations.   used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008). where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.41 e Å −3 Δρ min = −0.39 e Å −3 Extinction correction: SHELXL2014 (Sheldrick, 2015), Fc * =kFc[1+0.001xFc 2 λ 3 /sin(2θ)] -1/4 Extinction coefficient: 0.112 (13) 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.