Indole Ring System Research Articles

Crystal structure of dimethyl 3,3'-[(4-fluoro-phen-yl)methyl-ene]bis-(1H-indole-2-carboxyl-ate).

In the title compound, C27H21FN2O4, the mean planes of the indole ring systems (r.m.s. deviations = 0.0263 and 0.0160 Å) are approximately perpendic-ular to one another, making a dihedral angle of 84.0 (5)°; the fluoro-benzene ring is twisted with respect to the mean planes of the two indole ring systems at 89.5 (5) and 84.6 (3)°. In the crystal, pairs of N-H⋯O hydrogen bonds link the mol-ecules into inversion dimers, which are further linked by N-H⋯O hydrogen bonds into supra-molecular chains propagated along the b-axis direction. Weak C-H⋯π inter-actions are observed between neighbouring chains.

Crystal structures of three indole derivatives: 3-ethnyl-2-methyl-1-phenyl-sulfonyl-1H-indole, 4-phenyl-sulfonyl-3H,4H-cyclo-penta-[b]indol-1(2H)-one and 1-{2-[(E)-2-(5-chloro-2-nitro-phen-yl)ethen-yl]-1-phenyl-sulfonyl-1H-indol-3-yl}ethan-1-one chloro-form monosolvate.

The title compounds, C17H13NO2S, (I), C17H13NO3S, (II), and C24H17ClN2O5S·CHCl3, (III), are indole derivatives. Compounds (I) and (II) crystalize with two independent mol-ecules in the asymmetric unit. The indole ring systems in all three structures deviate only slightly from planarity, with dihedral angles between the planes of the pyrrole and benzene rings spanning the tight range 0.20 (9)-1.65 (9)°. These indole ring systems, in turn, are almost orthogonal to the phenyl-sulfonyl rings [range of dihedral angles between mean planes = 77.21 (8)-89.26 (8)°]. In the three compounds, the mol-ecular structure is stabilized by intra-molecular C-H⋯O hydrogen bonds, generating S(6) ring motifs with the sulfone O atom. In compounds (I) and (II), the two independent mol-ecules are linked by C-H⋯O hydrogen bonds and C-H⋯π inter-actions, while in compound (III), the mol-ecules are linked by C-H⋯O hydrogen bonds, generating R 2 (2)(22) inversion dimers.

Aromatic Interactions in Organocatalyst Design: Augmenting Selectivity Reversal in Iminium Ion Activation.

Substituting N-methylpyrrole for N-methyindole in secondary-amine-catalysed Friedel-Crafts reactions leads to a curious erosion of enantioselectivity. In extreme cases, this substrate dependence can lead to an inversion in the sense of enantioinduction. Indeed, these closely similar transformations require two structurally distinct catalysts to obtain comparable selectivities. Herein a focussed molecular editing study is disclosed to illuminate the structural features responsible for this disparity, and thus identify lead catalyst structures to further exploit this selectivity reversal. Key to effective catalyst re-engineering was delineating the non-covalent interactions that manifest themselves in conformation. Herein we disclose preliminary validation that intermolecular aromatic (CH-π and cation-π) interactions between the incipient iminium cation and the indole ring system is key to rationalising selectivity reversal. This is absent in the N-methylpyrrole alkylation, thus forming the basis of two competing enantio-induction pathways. A simple L-valine catalyst has been developed that significantly augments this interaction.

Crystal structure of 4-(2-azido-phen-yl)-5-benzoyl-2-(1H-indol-3-yl)-1H-pyrrole-3-carbo-nitrile.

In the title compound, C26H16N6O, the dihedral angles between the central pyrrole ring and the pendant indole ring system (r.m.s. deviation = 0.027 Å) and the azide-bearing benzene ring are 37.56 (8) and 51.62 (11)°, respectively. The azide group is almost coplanar with its attached benzene ring [C—C—N—N = 3.8 (3)°]. The benzoyl benzene ring is disordered over two orientations twisted with respect to each other by 9.29 (8)° in a 0.514 (2):0.486 (2) ratio. In the crystal, inversion dimers linked by pairs of Np—H⋯O (p = pyrrole) hydrogen bonds generate R 2 2(10) loops. A second inversion dimer arises from a pair of Ni—H⋯Nc (i = indole and c = cyanide) hydrogen bonds, which generates an R 2 2(16) loop. Together, the hydrogen bonds lead to [011] chains in the crystal.

Crystal structure of methyl 1-methyl-2-oxo-spiro-[indoline-3,2'-oxirane]-3'-carboxyl-ate.

In the title compound, C12H11NO4, the dihedral angle between the indole ring system (r.m.s. deviation = 0.019 Å) and the oxirane ring is 88.8 (2)°. The oxirane O atom and the bridging ester O atom are in an approximate syn conformation [O—C—C—O = −25.4 (3)°] In the crystal, inversion dimers linked by pair of C—H⋯O hydrogen bonds generate R 2 2(8) loops, where the C—H donor group forms part of the oxirane ring. A second C—H⋯O inter­action arising from one of the C—H groups of the benzene ring links the dimers into [001] double chains.

Crystal structure of methyl (E)-2-(1-methyl-2-oxoindolin-3-yl-idene)acetate.

The title compound, C12H11NO3, is essentially planar, with the mean plane of the acetate side chain [–C—C(=O)—O—C] being inclined to the mean plane of the indole ring system by 12.49 (7)°. The five- and six-membered rings of the indole group are almost coplanar, making a dihedral angle of 1.76 (8)°. The conformation about the C=C bond is E and there is an intra­molecular C—H⋯O hydrogen bond present. In the crystal, mol­ecules are linked by pairs of C—H⋯O hydrogen bonds forming inversion dimers, with an R 2 2(16) ring motif. The dimers are linked by a second pair of C—H⋯O hydrogen bonds, enclosing R 2 2(16) ring motifs, forming ribbons lying parallel to (-114). The ribbons are linked via C—H⋯π inter­actions, forming a three-dimensional structure.

Crystal structure of (2-bromo-methyl-1-phenyl-sulfonyl-1H-indol-3-yl)(phen-yl)methanone.

In the title compound, C22H16BrNO3S, the phenyl rings make dihedral angles of 84.81 (16) and 61.67 (17)° with the indole ring system (r.m.s. deviation = 0.012 Å), while the phenyl rings are inclined to one another by 69.5 (2)°. The mol­ecular structure is stabilized by weak intra­molecular C—H⋯O hydrogen bonds. The sulfonyl S atom has a distorted tetra­hedral configuration. In the crystal, there are no significant inter­molecular inter­actions present.

Crystal structure of (2-methyl-1-phenyl-sulfon-yl-1H-indol-3-yl)(phen-yl)methanone.

In the title compound, C22H17NO3S, the sulfonyl-bound phenyl ring is almost orthogonal to the indole ring system, making a dihedral angle of 84.89 (7)°. The carbonyl-bound phenyl ring forms a dihedral angle of 57.32 (5)° with the indole ring system. The two phenyl rings are inclined at 52.68 (7)°. The S atom has a distorted tetra-hedral configuration. In the crystal, weak C-H⋯O inter-actions link the mol-ecules, forming a helical chain along the b-axis direction.

Facile synthesis of 11-aryl-6H-isoindolo[2,1-a]indol-6-ones via hypervalent iodine(iii)-promoted cascade cyclization

An efficient method was developed for the synthesis of a tetracyclic fused indole and isoindoline ring system, under metal-free conditions.

Crystal structure of dimethyl 3,3'-[(3-fluoro-phenyl)methyl-ene]bis-(1H-indole-2-carboxyl-ate).

In the title compound, C27H21FN2O4, the mean planes of the two indole ring systems (r.m.s. deviations = 0.0166 and 0.0086 Å) are approximately perpendic-ular to one another, making a dihedral angle of 87.8 (5)°; the fluorobenzene ring is twisted with respect to the mean planes of the two indole ring systems at 82.7 (5) and 85.5 (3)°. In the crystal, pairs of N-H⋯O hydrogen bonds link the mol-ecules into the inversion dimers, which are further linked by N-H⋯O hydrogen bonds into supra-molecular chains propagating along the b-axis direction. Weak C-H⋯π inter-actions are observed between neighbouring chains.

Crystal structure of 3-[(E)-2-(4-phenyl-1,3-thia-zol-2-yl)hydrazin-1-yl-idene]indolin-2-one.

In the title mol­ecule, C17H12N4OS, the thia­zole ring forms a dihedral angle of 10.8 (2)° with the phenyl ring and an angle of 3.1 (3)° with the indole ring system [which has a maximum deviation of 0.035 (2) Å]. The dihedral angle between the planes of the phenyl ring and the indole ring system is 11.5 (1)°. An intra­molecular N—H⋯O hydrogen bond is observed. In the crystal, pairs of N—H⋯O hydrogen bonds form inversion dimers with an R 2 2(8) graph-set motif.

Crystal structure of dimethyl 3,3'-[(3-nitro-phen-yl)methyl-ene]bis-(1H-indole-2-carboxyl-ate) ethanol monosolvate.

In the title compound, C27H21N3O6·C2H5OH, the indole ring systems are approximately perpendicular to each other, with a dihedral angle of 89.3 (5)°; the plane of the benzene ring is oriented with respect to the indole ring systems at 49.9 (5) and 73.4 (3)°. In the crystal, mol-ecules are linked by N-H⋯O and O-H⋯O hydrogen bonds and weak C-H⋯π inter-actions into a three-dimensional supra-molecular architecture. A void of 33.0 (7) Å(3) is observed in the crystal structure. The solvent ethanol molecule acts as a donor, forming an O-H⋯O hydrogen bond, reinforcing the framework structure.

Crystal structure of 1-methyl-3-[2,2,2-tri-fluoro-1-(1-methyl-1H-indol-3-yl)-1-phenyl-eth-yl]-1H-indole.

The title compound, C26H21F3N2, was prepared by the palladium-catalysed reaction of (2,2,2-tri­fluoro­eth­yl)benzene with 1-methyl-1H-indole. The dihedral angle between the planes of the indole-ring systems is 52.13 (6)° and the N-methyl groups point away from each other. Three short intra­molecular C—H⋯F contacts are observed.

Crystal structure of dimethyl 3,3'-[(4-chloro-phen-yl)methyl-ene]bis-(1H-indole-2-carboxyl-ate).

In the title compound, C27H21ClN2O4, the mean planes of the two indole ring systems (r.m.s. deviations = 0.021 and 0.024 Å) are approximately perpendicular to one another, with a dihedral angle of 79.54 (12)°. The benzene ring is twisted with respect to the mean planes of the two indole ring systems at angles of 80.14 (15) and 86.30 (15)°. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds, forming inversion dimers with an R (2) 2(18) ring motif. The dimers are linked by a further N-H⋯O hydrogen bond, forming chains along [100]. There are intra- and inter-molecular C-H⋯π inter-actions present, the latter linking the chains to form a three-dimensional supra-molecular structure.

ChemInform Abstract: Synthesis of a Benzannulated Pyrrolizidine by a Copper‐Catalyzed Intramolecular α‐Arylation Reaction.

A synthetic route to the pyrrolo[1,2-a]indole ring system (benzannulated pyrrolizidine) involving a base-induced intramolecular aza-Michael reaction as the key CN bond-forming penultimate step, followed by a Cu-catalyzed intramolecular α-arylation reaction, to provide the tricyclic framework over six steps is described.

Crystal structure of 2-(2-bromo-phen-yl)-4-(1H-indol-3-yl)-6-(thio-phen-2-yl)pyridine-3-carbo-nitrile.

In the title compound, C24H14BrN3S, the dihedral angles between the planes of the pyridine ring and the pendant thio­phene ring, the indole ring system (r.m.s. deviation = 0.022 Å) and the bromo­benzene ring are 9.37 (17), 21.90 (12) and 69.01 (15)°, respectively. The approximate coplanarity of the central ring and the indole ring system is supported by two intra­molecular C—H⋯N inter­actions. In the crystal, inversion dimers linked by pairs of N—H⋯N hydrogen bonds generate R 2 2(16) loops and the dimers are linked by C—H⋯π and aromatic π–π stacking [shortest centroid–centroid separation = 3.729 (3) Å] into a three-dimensional network.

Molecular Structure and Density Functional Theory Calculations of 3-(3-Nitrothien-2-yl)indole: Structural and Vibrational Analysis

An X-ray diffraction study along with crystal supramolecular analysis of 3-(3-nitrothien-2-yl)indole, I, were carried out. The crystals are orthorhombic; C12H8N2O2S; M = 244.26; a = 13.3286 (6) A, b = 7.5109 (4) A, c = 21.8144 (9) A; α = β = γ = 90°; V = 2183.83 (18) A3, d c = 1.486 g/cm3, Z = 8, space group Pbca. The crystal structure of the title compound consists of two planar rings, the indole ring and the substituted thiophene ring. The inter-planar angle between the indole ring system and thiophene ring is 34.39°. The dihedral angle of the NO2 plane and the thiophene plane is 5.09°. The crystal packing shows crystal supramolecularity in which molecules are connected via different C–H···O, N–H···C(π) intermolecular interactions with edge-to-face and offset-face-to-face aryl···aryl, interactions consolidating three-dimensional network. The molecular geometry and vibrational frequencies of (C12H8N2O2S) in the ground state have been calculated by using density functional method (DFT/B3LYP) with 6-311++G(d,p) basis set. The optimized geometric bond lengths and bond angles and IR stretching frequencies obtained show good agreement with the experimental data. The crystal structure reveals different crystal supramolecularity motifs via C–H···O, N–H···C(π) and edge-to-face and offset-face-to-face aryl···aryl, interactions consolidating three-dimensional network. Density functional method (DFT/B3LYP) with 6-311++G(d,p) basis set of the obtained optimized geometric and IR stretching frequencies show good agreement with the experimental data.

ChemInform Abstract: The Synthesis of Vinylogous Amidine Heterocycles.

We report herein a convenient synthetic methodology for the conversion of meta-dinitro heterocyclic rings to iminoquinones with vinylogous amidine functionality. These structures are found in nature, particularly in marine organisms, and may be important for the pigments and biological activity observed with such marine secondary metabolites. Using benzimidazole and indole ring systems we show the versatility of these vinylogous amidines for organic synthesis, including the following: transamination substitution reactions with virtually any primary amine, regional control of the substitution with substituents between the vinylogous amidine, and hydrolytic properties that can be controlled or optimized based on the properties of the chosen ring system. Taken together, this versatile chemistry and functionalization of organic molecules may be useful in the preparation of a variety of chemical products such as drug pharmacophores or assembling macromolecular structures.

Synthesis of a Benzannulated Pyrrolizidine by a Copper‐Catalyzed Intramolecular α‐Arylation Reaction

AbstractA synthetic route to the pyrrolo[1,2‐a]indole ring system (benzannulated pyrrolizidine) involving a base‐induced intramolecular aza‐Michael reaction as the key CN bond‐forming penultimate step, followed by a Cu‐catalyzed intramolecular α‐arylation reaction, to provide the tricyclic framework over six steps is described.

Methyl 3'-(2,5-di-methyl-benz-yl)-1'-methyl-2-oxo-4'-phenyl-spiro-[indoline-3,2'-pyrrolidine]-3'-carboxyl-ate chloro-form monosolvate.

In the title solvate, C29H30N2O3·CHCl3, the dihedral angle between the indole ring system (r.m.s. deviation = 0.050 Å) and the 4-methyl­pyrrolidine ring is 88.88 (8)°. The latter ring adopts an envelope conformation with the N atom as the flap. Its mean plane makes dihedral angles of 86.94 (11) and 42.08 (9)° with the phenyl and di­methyl­benzene rings, respectively. The mol­ecular conformation is stabilized by intra­molecular C—H⋯O hydrogen bonds, which generate S(6) and S(9) ring motifs. The chloro­form solvent mol­ecule is linked to the organic mol­ecule by a C—H⋯O hydrogen bond involving the carbonyl O atom of the carboxyl­ate group. In the crystal, mol­ecules are linked via bifurcated N—H⋯(N,O) and C—H⋯O hydrogen bonds, forming chains propagating along [001].