Crystal structure of [4-(2-meth-oxy-phen-yl)-3-methyl-1-phenyl-6-tri-fluoro-methyl-1H-pyrazolo-[3,4-b]pyridin-5-yl](thio-phen-2-yl)methanone.

The title compound, C26H18F3N3O2S, a 2-meth-oxy-substituted derivative, is closely related to its 4-methyl- and 4-chloro-substituted analogues and yet displays no structural relationships with them. The thio-phene ring is disorder free and the -CF3 group exhibits disorder, respectively, in contrast and similar to that observed in the 4-methyl- and 4-chloro-substituted derivatives. The torsion angle which defines the twist of the thio-phene ring is -69.6 (2)° (gauche) in the title compound, whereas it is anti-clinal in the 4-methyl- and 4-chloro-substituted derivatives, with respective values of 99.9 (2) and 99.3 (2)°. The absence of disorder in the thio-phene ring facilitates one of its ring C atoms to participate in the lone inter-molecular C-H⋯O hydrogen bond present in the crystal, leading to a characteristic C(5) chain graph-set motif linking mol-ecules related through glides along [010]. An intra-moleculr C-H⋯N hydrogen bond also occurs.

Crystal structure of 4-sulfamoylanilinium di-hydrogen phosphate.

In the crystal structure of the title mol-ecular salt, C6H9N2O2S(+)·H2PO4 (-), the sulfomylalinium cations and the di-hydrogen phosphate anions form independent [100] chains through Ns-H⋯O (s = sulfamo-yl) and O-H⋯O hydrogen bonds, respectively. The chains are cross-linked by Na-H⋯O (a = amine) hydrogen bonds, generating (010) sheets. Two C-H⋯O hydrogen bonds involving diametrically opposite C atoms in the benzene ring of the cation as donors form chains parallel to [202] in which P=O and P-OH groups are acceptors. Together, these inter-actions lead to a three-dimensional network.

Isomorphous methyl- and chloro-substituted small heterocyclic analogues obeying the chlorine-methyl (Cl-Me) exchange rule.

The two new isomorphous structures [3-methyl-4-(4-methylphenyl)-1-phenyl-6-trifluoromethyl-1H-pyrazolo[3,4-b]pyridin-5-yl](thiophen-2-yl)methanone, C26H18F3N3OS, (I), and [4-(4-chlorophenyl)-3-methyl-1-phenyl-6-trifluoromethyl-1H-pyrazolo[3,4-b]pyridin-5-yl](thiophen-2-yl)methanone, C25H15ClF3N3OS, (II), are shown to obey the chlorine-methyl exchange rule. Both structures show extensive disorder, treatment of which greatly improves the quality of the description of the structures. In addition, it is worth noting that the presence of extensive disorder may make it difficult to detect the isomorphism automatically during data-mining procedures (such as searches of the Cambridge Structural Database).

Supramolecular architectures of N-acetyl-L-proline monohydrate and N-benzyl-L-proline.

The title compounds, N-acetyl-L-proline monohydrate, C7H11NO3·H2O, (I), and N-benzyl-L-proline, C12H15NO2, (II), crystallize in the monoclinic space group P21 with Z' = 1 and Z' = 2, respectively. The conformation of C(γ) with respect to the carboxylic acid group in (I) is C(γ)-exo or UP pucker, with the pyrrolidine ring twisted, while in (II), it is C(γ)-endo or DOWN, with the pyrrolidine ring assuming an envelope conformation. The crystal packing interactions in (I) are composed of two substructures, one characterized by an R6(6)(24) motif through O-H...O hydrogen bonds and the other by an R4(4)(23) ring through C-H...O interactions. In (II), the crystal packing interactions consist of N-H...O and C-H...O hydrogen bonds. Proline (Pro) exists in its neutral form in (I) and is zwitterionic in (II). This difference in the ionization states of Pro is manifested through the absence of N-H...O and presence of O-H...O interactions in (I), and the presence of N-H...O and absence of O-H...O hydrogen bonds in (II). While C-H...O interactions are present in both (I) and (II), the geometry of the synthons formed by them and their mode of participation in intermolecular interactions is different. Though the title compounds differ significantly in terms of modifications in the Pro skeleton, the differences in their supramolecular structures may also be viewed as a result of the molecular recognition facilitated by the presence of a solvent water molecule in (I) and the zwitterionic state of the amino acid in (II).

4-Cyano-N-ethyl-spiro-[chromene-2,4'-piperidine]-1'-carboxamide.

The title compound, C17H19N3O2, crystallizes with two independent mol-ecules (A and B) in the asymmetric unit. In both mol-ecules, the pyran ring has a twisted conformation ((5)S4), with Q = 0.301 (3) Å, θ = 116.7 (6) and ϕ= 213.6 (7)° for mol-ecule A, and Q = 0.364 (2) Å, θ = 113.7 (3) and ϕ = 213.0 (4)° for mol-ecule B. In mol-ecule B, the terminal ethyl group is disordered over two orientations with an occupancy ratio of 0.55 (1):0.45 (1). In the crystal, mol-ecules A and B form very similar but separate R1(2)(7) motifs through N-H⋯O and C-H⋯O hydrogen bonds. The resulting chains along [001] are inter-linked by weaker C-H⋯O and C-H⋯π inter-actions, forming layers parallel to the bc plane.

N-But-oxy-carbonyl-5-oxo-l-proline ethyl ester.

The mol-ecular structure of the title compound, C12H19NO5, may be visualized as made up of two nearly perpendicular planes [dihedral angle = 87.39 (12)°] and its crystal structure is a good example of C-H⋯O inter-actions assuming significance in optimizing supra-molecular aggregation in crystals in a mol-ecule which is severely imbalanced in terms of donors to acceptor atoms. The pyrrolidine ring adopts a ((3) T 2) twist conformation with puckering parameters Q = 0.2630 (4) Šand ϕ = 59 (9)°. The crystal structure features R 2 (4)(10) and R 3 (4)(26) ring motifs formed by four weak C-H⋯O inter-actions, leading to supra-molecular sheets lying parallel to the bc plane.

N-tert-But-oxy-carbonyl-α-(2-fluoro-benzyl)-l-proline.

In the title compound, C17H22FNO4, the pyrrolidine ring adopts an envelope conformation with the disordered com-ponents of the methylene C atom, with site occupancies of 0.896 (7) and 0.104 (7), being the flap on either side of the mean plane involving the other atoms of the ring. The carb-oxy-lic acid group forms dihedral angles of 72.06 (11) and 45.44 (5)° with the N-tert-but-oxy-carbonyl group and the 2-fluoro-benzyl group, respectively. In the crystal, two-dimensional layers of mol-ecules parallel to (001) are built through an R 4 (4)(23) motif generated via O-H⋯O, C-H⋯O and C-H⋯F inter-actions, and an R 2 (2)(11) motif generated by C-H⋯O and C-H⋯F inter-actions.

Supramolecular sheets in (4H-chromeno[4,3-c]isoxazol-3-yl)methanol and its hydrated 8-methyl-substituted analogue at 100 K.

The title compounds, (4H-chromeno[4,3-c]isoxazol-3-yl)methanol, C(11)H(9)NO(3), (I), and (8-methyl-4H-chromeno[4,3-c]isoxazol-3-yl)methanol monohydrate, C(12)H(11)NO(3)·H(2)O, (II), crystallize in the monoclinic space groups P2(1)/c and C2/c, respectively. The simple addition of a methyl substituent in (II) results in a change in the structure type and substantially alters the intermolecular interaction patterns, while retaining the point-group symmetry 2/m. Compound (II) crystallizes as a hydrate and the resulting hydrogen-bonding interactions involving the water molecule are the cause of differences in the hydrogen-bonded supramolecular motifs present in (I) and (II). The water molecule in (II) is disordered over two positions having very similar orientations, with occupancies of 0.571 (18) and 0.429 (18), although the pattern of hydrogen-bonding interactions for the two disordered water molecules remains essentially the same. In both compounds, the primary donor hydroxy group adopts a trans conformation with respect to the isoxazole O atom, with a torsion angle of 170.65 (8)° for (I) and 179.56 (10)° for (II), the small difference being due to differences in the hydrogen-bonding environment of the hydroxy group. In (I), molecules are linked through two independent O-H···N and C-H···O hydrogen bonds and form sheets of centrosymmetric R(4)(4)(18) and R(4)(4)(14) rings extending parallel to the (100) plane. The supramolecular motifs in (II) generate two-dimensional sheets parallel to the (100) plane through a combination of O-H···X (X = N, O) and C-H···O hydrogen bonds, leading to water-assisted noncentrosymmetric R(2)(2)(8) and R(6)(6)(20) motifs. The present work is an example of how the simple replacement of a substituent in the main molecular scaffold may transform the structure type, paving the way for a variety of supramolecular motifs and consequently altering the complexity of the intermolecular interaction patterns.

Supramolecular networks in (9-fluoro-4H-chromeno[4,3-c]isoxazol-3-yl)methanol and its 9-chloro analogue at 100 K.

The title compounds, (9-fluoro-4H-chromeno[4,3-c]isoxazol-3-yl)methanol, C(11)H(8)FNO(3), (I), and (9-chloro-4H-chromeno[4,3-c]isoxazol-3-yl)methanol, C(11)H(8)ClNO(3), (II), crystallize in the orthorhombic space group Pbca with Z' = 1 and the triclinic space group P-1 with Z' = 6, respectively. The simple replacement of F by Cl in the main molecular scaffold of (I) and (II) results in significant differences in the intermolecular interaction patterns and a corresponding change in the point-group symmetry from D(2h) to C(i) = S(2). These striking differences are manifested through the presence of C-H···F and the absence of O-H···O and C-H···O interactions in (I), and the absence of C-H···Cl and the presence of O-H···O and C-H···O interactions in (II). However, the geometry of the synthons formed by the O-H···N and O-H···X (X = F or Cl) interactions observed in the constitution of the supramolecular networks of both (I) and (II) remains similar. Also, C-H···O interactions are not preferred in the presence of F in (I), while they are much preferred in the presence of Cl in (II).

1'-Benzylspiro-[chromene-2,4'-piperi-dine]-4-carbonitrile.

In the title compound, C(21)H(20)N(2)O, the piperidine ring adopts a chair conformation while the pyran ring adopts a screw-boat conformation. The piperidine ring forms dihedral angles of 65.75 (3) and 67.79 (5)° with the chroman and methyl-substituted benzene rings, respectively. The crystal structure features weak C-H⋯π and π-π [centroid-centroid distance = 3.8098 (8) Å] inter-actions.

2-Amino-4-(4-chloro-phen-yl)-5,6,7,8,9,10-hexa-hydro-benzo[8]annulene-1,3-dicarbonitrile.

In the title compound, C(20)H(18)ClN(3), the cyclo-octene ring exhibits conformational disorder of two methyl-ene groups with a site-occupation factor of 0.859 (6) for the major occupied site. In the crystal, mol-ecules are connected into inversion dimers via pairs of weak N-H⋯N hydrogen bonds, forming an R(2) (2)(12) graph-set motif. These dimers are further connected via weak N-H⋯Cl inter-actions into chains running along [011]. There are also C-H⋯N interactions present in the crystal.

5-Benzoyl-2-(1H-indol-3-yl)-4-[4-(propan-2-yl)phen-yl]-4,5-dihydro-furan-3-carbonitrile.

In the title compound, C29H24N2O2, the hydrofuran ring is twisted with puckering parameters Q = 0.1553 (16) Šand ϕ = 305.0 (6)°. In the crystal, the graph-set motifs of the inter-action pattern are an R2(2)(16) motif involving dimers through N-H⋯N hydrogen bonds across centres of inversion and a C(6) motif through C-H⋯O hydrogen-bond between glide-related mol-ecules. Together, these generate [101] ladder-like chains.

5-(4-Fluoro-benzyl-idene)-4'-(4-fluoro-phen-yl)-1,1'-dimethyl-dispiro-[piperidine-3,3'-pyrrolidine-2',3''-indoline]-4,2''-dione.

The asymmetric unit of the title compound, C(30)H(27)F(2)N(3)O(2), contains two independent mol-ecules. The pyrrolidine five-membered ring assumes an envelope conformation (with the CH(2) atom at the flap) in one mol-ecule and a twisted conformation in the other one. In both independent mol-ecules, the 4-piperidinone rings adopt a similar twisted chair conformation. In the crystal, the two independent mol-ecules form an R(2) (2)(8) dimer through a pair of N-H⋯O hydrogen bonds; the R(2) (2)(8) dimers are connected via weak C-H⋯O hydrogen bonds, leading to a chain extending along the c axis.

1-Methyl-1'-(4-methyl-phen-yl)-2',3',5',6',7',7a'-hexa-hydro-1'H-dispiro-[piperidine-3,2'-pyrrolizine-3',3''-indoline]-4,2''-dione.

The title compound, C(26)H(29)N(3)O(2), crystallizes with two mol-ecules in the asymmetric unit, having C-H⋯O inter-actions between them and resulting in a dimer characterized by an R(2) (2)(11) motif. These dimers are linked into an ABABAB chain via N-H⋯O, N-H⋯N and C-H⋯O built edge-fused R(1) (2)(5) and R(2) (2)(7) motifs. This chain is linked to its inversion-related partner via N-H⋯O bonds with an R(2) (2)(8) motif and leads to a double chain extending along the b axis characterized by an R(6) (6)(36) motif across the inversion centres. The methyl group of the phenyl ring and the oxindole of mol-ecule A and B are involved in C-H⋯π inter-actions. One C atom of the pyrrolizine ring of mol-ecule A and its attached H atoms show positional disorder, the major and minor components being in the ratio 0.706 (7):0.294 (7).

Crystal structure and Hirshfeld surface analysis of a pyrrolo-thia-zine complex.

In the title compound, diethyl 2,2-dioxo-4-(thio-phen-2-yl)-1-[(thio-phen-2-yl)meth-yl]-3,4,6,7,8,8a-hexa-hydro-1H-pyrrolo-[2,1-c][1,4]thia-zine-1,3-di-carboxyl-ate, C22H28NO6S3, the pyrrolo ring is in an envelope conformation while the thia-zine ring adopts a near chair conformation. The dihedral angles between the thia-zine ring and the methyl-thienyl, thienyl and pyrrolo rings are 64.0 (2), 87.92 (7) and 5.6 (2)°, respectively. In the crystal, the mol-ecules are linked by weak C-H⋯O hydrogen bonds. A Hirshfeld surface analysis was performed to investigate the inter-molecular inter-actions. Disorder of the methyl-thienyl group with site occupancies of 0. 792 (3) and 0.208 (3) is observed.

8-(2-Chloro-phen-yl)-1-(4-chloro-phen-yl)-4-[(E)-(2-chloro-phen-yl)methyl-idene]-6-methyl-4,5,6,7,7a,8-hexa-hydro-1,2,4-oxadiazolo[5,4-d]pyrido[3,4-c][1,5]benzothia-zepine.

In the title compound, C(33)H(26)Cl(3)N(3)OS, the oxadiazole, piperidine and benzothia-pezine rings adopt envelope, chair and twist-boat conformations, respectively. In the crystal, the mol-ecular aggregation is characterized by chains of centrosymmetrically related pairs connected through Cl⋯Cl inter-actions [3.533 (2) Å], extending parallel to (202).

4'-(2,4-Dichloro-phen-yl)-1,1'-dimethyl-piperidine-3-spiro-3'-pyrrolidine-2'-spiro-3''-indoline-4,2''-dione.

In the title compound, C(23)H(23)Cl(2)N(3)O(2), the pyrroline ring adopts an envelope conformation and the piperidinone ring assumes a slightly twisted chair form. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate an R(2) (8) graph-set motif and a short Cl⋯Cl contact of 3.478 (1) Šoccurs.

Crystal structure and mol-ecular Hirshfeld surface analysis of acenaphthene derivatives obeying the chlorine-methyl exchange rule.

Instances of crystal structures that remain isomorphous in spite of some minor changes in their respective mol-ecules, such as change in a substituent atom/group, can provide insights into the factors that govern crystal packing. In this context, an accurate description of the crystal structures of an isomorphous pair that differ from each other only by a chlorine-methyl substituent, viz. 5''-(2-chloro-benzyl-idene)-4'-(2-chloro-phen-yl)-1'-methyl-dispiro-[acenaphthene-1,2'-pyrrolidine-3',3''-piperidine]-2,4''-dione, C34H28Cl2N2O2, (I), and its analogue 1'-methyl-5''-(2-methyl-benzyl-idene)-4'-(2-methyl-phen-yl)di-spiro-[acenaphthene-1,2'-pyrrolidine-3',3''-piperidine]-2,4''-dione, C36H34N2O2, (II), is presented. While there are two C-H⋯O weak inter-molecular inter-actions present in both (I) and (II), the change of substituent from chlorine to methyl has given rise to an additional weak C-H⋯O inter-molecular inter-action that is relatively stronger than the other two. However, the presence of the stronger C-H⋯O inter-action in (II) has not disrupted the validity of the chloro-methyl exchange rule. Details of the crystal structures and Hirshfeld analyses of the two compounds are presented.

Isomorphous diethyl 1-(4-chloro-benz-yl)-4-(4-chloro-phen-yl)-2,2-dioxo-3,4,6,7,8,8a-hexa-hydro-1H-pyrrolo-[2,1-c][1,4]thia-zine-1,3-di-carboxyl-ate and its 1-(4-methyl-benz-yl)-4-(4-methyl-phen-yl)-substituted analogue obeying the chloro-methyl exchange rule.

Accurate studies on the effect of substituents on the crystal packing are essential for understanding the inter-molecular inter-actions and thus paving the way to crystal structure prediction. The crystal structures of diethyl 1-(4-chloro-benz-yl)-4-(4-chloro-phen-yl)-2,2-dioxo-3,4,6,7,8,8a-hexa-hydro-1H-pyrrolo-[2,1-c][1,4]thiazine-1,3-di-carboxyl-ate, C26H29Cl2NO6S, (I), and its isomorphous pair diethyl 1-(4-methyl-benz-yl)-4-(4-methyl-phen-yl)-2,2-dioxo-3,4,6,7,8,8a-hexa-hydro-1H-pyrrolo-[2,1-c][1,4]thia-zine-1,3-di-carboxyl-ate, C28H35NO6S, (II), are described. The mol-ecular aggregation patterns appear to be strikingly similar despite changes in the substituents, with a Cl atom in (I) being replaced by a methyl group in (II). Inspite of the chemical modifications, the structures of (I) and (I) are isomorphous, isostructural and found to obey the chlorine-methyl exchange rule. Both the structures feature C-H⋯O hydrogen bonding. However, a distinguishing feature between (I) and (II) is observed in the conformation of the pyrrole rings where the twist occurs on different C-N bonds. Hirshfeld analysis of both structures is presented and discussed.

Crystal structures of 2'-benzoyl-1'-(4-methyl-phenyl)-1,1',2,2',5',6',7',7a'-octa-hydro-spiro-[indole-3,3'-pyrrolizin]-2-one and 2'-(4-bromo-benzoyl)-1'-(2-chloro-phen-yl)-1,1',2,2',5',6',7',7a'-octa-hydro-spiro-[indole-3,3'-pyrrolizin]-2-one.

The two title compounds, C28H26N2O2, (I), and C27H22BrClN2O2, (II), differ in their substituents, viz.4-methyl-phenyl and benzoyl rings in (I) replaced by 2-chloro-phenyl and 4- bromo-benzoyl, respectively, in (II). A significant difference between the two mol-ecules is found in the deviation of the benzoyl O atom from the least-squares plane of the ring to which it is attached [0.593 (4) and 0.131 (3) Å, respectively], a fact which may be attributed to the different participation of the benzoyl O atoms as acceptors in their inter-molecular C-H⋯O inter-actions. The chemical modifications in (I) and (II) do not seem to affect the type nor strength of the inter-molecular N-H⋯N and C-H⋯O hydrogen bonds responsible for the two crystal structures, such that the aggregation of mol-ecules appears similar in spite of the mol-ecular changes.