Three closely related 1-[(1,3-benzodioxol-5-yl)methyl]-4-(halobenzoyl)piperazines: similar molecular structures but different intermolecular interactions

Three 1-[(1,3-benzodioxol-5-yl)methyl]-4-(halobenzoyl)piperazines adopt very similar molecular conformations but, while the molecules of the 3-fluorobenzoyl are linked by hydrogen bonds into a three-dimensional structure, there are no hydrogen bonds in either of the 2,6-difluorobenzoyl and 2,4-dichlorobenzoyl analogues.


Structural commentary
In each of (I)-(III), the five-membered ring is slightly nonplanar: while the atoms O11, C7A, C3A and O13 are coplanar, as expected, the atom C12 is slightly displaced from this plane by 0.150 (2), 0.099 (6) and 0.210 (2) Å in (I)-(III), respectively, giving an envelope conformation in each case, with the ring folded across the line O11Á Á ÁO13. The piperazine rings all adopt chair conformations with the substituent at atom N1 in an equatorial site, while the atoms of the amide fragment (C3, N4, C5, C47, O47 and C41) are coplanar. The only significant conformational difference between the molecules in (I)-(III) lies in the dihedral angle between the amide unit and the adjacent aryl ring (C41-C46), 62.97 (5) in (I) but 77.72 (12) and 75.50 (5) in (II) and (III), respectively. The molecules of (I)-(III) exhibit no internal symmetry and hence they are all conformationally chiral, but the space groups (Table 2) confirm that equal numbers of the two conformational enantiomorphs are present in each crystal.

Supramolecular features
Despite their similar molecular constitutions and conformations, compounds (I)-(III) all exhibit different types of direction-specific intermolecular interactions. In the crystal structure of compound (I), a combination of one C-HÁ Á ÁO hydrogen bond and two C-HÁ Á Á(arene) hydrogen bonds (Table 1) links the molecules into a three-dimensional framework structure, whose formation can readily be analysed in terms of simple sub-structures (Ferguson et al., 1998a,b;Gregson et al., 2000). The C-HÁ Á ÁO hydrogen bond links molecules related by the 2 1 screw axis along (0.25, y, 0.25) to form a C(5) (Etter, 1990;Etter et al., 1990;Bernstein et al., 1995) chain running parallel to the [010] direction. In addition, the C-HÁ Á Á(arene) hydrogen bond having atom C5 as the donor links molecules related by the 2 1 screw axis along (0.75, y, 0.25) into a second chain running parallel to [010] and, together, these two interactions generate a sheet lying parallel to (001) (Fig. 4)  The molecular structure of compound (II) showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.

Figure 3
The molecular structure of compound (III) showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.

Figure 1
The molecular structure of compound (I) showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. Table 1 Hydrogen-bond geometry (Å , ) for (I).
by the n-glide plane at y = 0.75 into a chain running parallel to the [101] direction (Fig. 5), and chains of this type link the (001) sheets into a continuous three-dimensional structure. It is interesting to note that both C-HÁ Á Á(arene) hydrogen bonds utilize the same ring as the acceptor, with one donor approaching each face of this ring (Fig. 6), with the angle H5 i Á Á ÁCg1Á Á ÁH45 ii = 152 , where Cg1 represents the centroid of the ring (C3A, C14, C15, C16, C17, C7A) and the symmetry codes are (i) 3 2 À x, À 1 2 + y, 1 2 À z) and (ii) ( 1 2 + x, 3 2 À y, À 1 2 + z). Hence, the two molecules providing the donor atoms here are related by inversion across (1, 1/2, 0). In this structure, the atoms of type O11 in the molecules at (x, y, z) and (2 À x, 1 À y, Àz) are separated by a distance of only 2.7888 (18) Å . At the same time, the atoms C12 and H12 at (x, y, z) are distant from O11 at (2 À x, 1 À y, Àz) by 2.66 and 3.008 (2) Å , respectively, with an associated C-HÁ Á ÁO angle of 101 ; the HÁ Á ÁO distance is too long and the C-HÁ Á ÁO angle is too small for this contact to be regarded as a hydrogen bond, but the short OÁ Á ÁO distance here is perhaps associated with this 'failed' hydrogen bond involving atom C12.
In contrast to the three-dimensional supramolecular assembly in (I) generated by three hydrogen bonds, the only direction-specific intermolecular interaction in (II) is a single C-HÁ Á ÁO contact, in which the D--HÁ Á ÁA angle is only 123 so that this cannot be regarded as structurally significant (Wood et al., 2009). The only direction-specific intermolecular interactions in (III) are a C-ClÁ Á Á(ring) contact involving the 1,3-dioxolane ring, but since this ring is not aromatic, this contact cannot be regarded as structurally significant; and a short ClÁ Á ÁCl contact between inversion-related pairs of molecules. For the atoms of type Cl44 in the molecules at (x, y, Part of the crystal structure of compound (I) showing the formation of a sheet lying parallel to (001) and built from C-HÁ Á ÁO and C-HÁ Á Á(arene) hydrogen bonds, which are drawn as dashed lines. For the sake of clarity, the H atoms bonded to the C atoms not involved in the motifs shown have been omitted.

Figure 5
Part of the crystal structure of compound (I) showing the formation of a chain running parallel to [101] and built from C-HÁ Á Á(arene) hydrogen bonds, which are drawn as dashed lines. For the sake of clarity, the H atoms not involved in the motifs shown have been omitted. z) and (Àx, Ày, 2 À z), the ClÁ Á ÁCl i distance is 3.3963 (7) Å with an associated C-ClÁ Á ÁCl i angle of 137.68 (5) [symmetry code: (i) Àx, Ày, 2 À z]. For C-ClÁ Á ÁCl angles of 90 and 180 , values of 1.78 and 1.58 Å have been suggested (Nyburg & Faerman, 1985) for the major and minor van der Waals radii: on this basis, a value of around 1.68 Å would seem appropriate to a C-ClÁ Á ÁCl angle close to 135 , so that the observed ClÁ Á ÁCl contact distance in (III) is not exceptional, and is probably therefore of no structural significance. Thus for both (II) and (III), the molecular packing depends solely on molecular shape and van der Waals forces.

Synthesis and crystallization
1-[(1,3-Benzodioxol-5-yl)methyl]piperazine was purchased from Sigma-Aldrich and used as received. For the synthesis of compounds (I)-(III), 1-(3-dimethylaminopropyl)-3-ethylcarbodimide (207 mg, 1.08 mmol), 1-hydroxybenzotriazole (121.6 mg, 0.9 mmol) and triethylamine (0.5 ml, 3.7 mmol) were added to solutions of the appropriately substituted benzoic acid [3-fluorobenzoic acid for (I), 2,6-difluorobenzoic acid for (II) or 2,4-dichlorobenzoic acid for (III)] (0.9 mmol) in N,N-dimethylformamide (5 ml) and the resulting mixtures were then stirred at 273 K for 20 min. A solution of 1-[(1,3benzodioxol-5-yl)methyl]piperazine (200 mg, 0.9 mmol) in N,N-dimethylformamide (5 ml) was then added to each mixture and stirring was continued overnight at ambient temperature. When the reactions were complete as confirmed using thin-layer chromatography, an excess of water was added to each of the mixtures, which were then exhaustively extracted using ethyl acetate. Each of the organic fractions was then washed successively with aqueous hydrochloric acid (1 mol dm À3 ), then with a saturated aqueous solution of sodium hydrogencarbonate, and finally with brine. The organic fractions were then dried over anhydrous sodium sulfate and concentrated under reduced pressure. Slow evaporation of these solutions, at ambient temperature and in the presence of air, gave crystals of compounds (I)-(III) suitable for single-crystal X-ray diffraction: m.p. (I) 383-386 K, (II) 373 K, (III) 394-396 K.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. All H atoms were located in difference maps, and they were subsequently treated as riding atoms in geometrically idealized positions with C-H distances 0.95 Å (aromatic) or 0.99 Å (CH 2 ) and with  Part of the crystal structure of compound (I) showing the two C-HÁ Á Á(arene) hydrogen bonds with a common aryl acceptor. The hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the unit-cell outline and the H atoms bonded to the C atoms not involved in the motifs shown have been omitted. The atoms marked with an asterisk (*) or a hash (#) are at the symmetry positions ( 1 2 + x, 3 2 À y, À 1 2 + z) and ( 3 2 À x, À 1 2 + y, 1 2 À z), respectively.
U iso (H) = 1.2U eq (C). For compound (I), fifteen bad outlier reflections were omitted from the data set. For compound (II), the correct orientation of the structure with respect to the polar axis direction could not be established because of the lack of significant resonant scattering: thus calculation of the Flack x parameter (Flack, 1983) using using 1369 quotients of the type [(I + ) À (I À )]/[(I + ) + (I À )] (Parsons et al., 2013) gave a value À0.3 (10), which must be regarded as indeterminate (Flack & Bernardinelli, 2000), despite the 93% coverage of Friedel pairs, while the value of the Hooft y parameter (Hooft et al., 2008), y = À0.2 (6), is likewise indeterminate.  For all structures, data collection: APEX2 (Bruker, 2004); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013 (Spek, 2009). where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.24 e Å −3 Δρ min = −0.18 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.

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 N1 0.36051 (17   where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.37 e Å −3 Δρ min = −0.37 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.