Intermolecular stacking in pyrazolo[3,4‐d]pyrimidine‐based pentamethylene‐linked flexible ­molecules

The crystal structures of 1‐{5‐[4,6‐bis­(methyl­sulfanyl)‐2H‐py­razolo­[3,4‐d]­pyrimidin‐2‐yl]­pentyl}‐6‐methyl­sulfanyl‐4‐(pyr­rolidin‐1‐yl)‐1H‐pyrazolo­[3,4‐d]­pyrimidine, C₂₂H₂₉N₉S₃, and 6‐methyl­sulfanyl‐1‐{5‐[6‐methyl­sulfanyl‐4‐(pyrrolidin‐1‐yl)‐2H‐pyrazolo­[3,4‐d]­pyrimidin‐2‐yl]­pentyl}‐4‐(pyrrolidin‐1‐yl)‐1H‐pyrazolo­[3,4‐d]­pyrimidine, C₂₅H₃₄N₁₀S₂, which differ in having either a pyrrolidine substituent or a methylsulfanyl group, show intermolecular stacking due to aromatic π–π interactions between the pyrazolo­[3,4‐d]­pyrimidine rings.     

A stacked pyrazolo[3,4‐d]pyrimidine‐based flexible molecule: the effect of a bulky benzyl group on intermolecular stacking in comparison with methyl and ethyl groups

In the crystal structure of 1,1′‐(1,3‐propane­diyl)­bis(5‐benzyl‐6‐methyl­sulfanyl‐4,5‐di­hydro‐1H‐pyrazolo­[3,4‐d]­pyrimidin‐4‐one), C₂₉H₂₈N₈O₂S₂, the pairs of pyrazolo­[3,4‐d]­pyrimidine rings stack as a result of intramolecular π–π interactions between the heterocyclic rings. The folded mol­ecules are further stacked in pairs, due to intermolecular aromatic π–π interactions and C—H?O hydrogen bonds.     

A stacked pyrazolo[3,4-d]pyrimidine-based flexible molecule: the effect on stacking of an ethyl group in comparison with a methyl group

In the crystal structure of 1,1′-(1,3-propane­diyl)­bis(5-ethyl-6-methyl­thio-4,5-di­hydro-1H-pyrazolo­[3,4-d]­pyrimidin-4-one), C₁₉H₂₄N₈O₂S₂, the pairs of pyrazolo­[3,4-d]­pyrimidine rings of the mol­ecule stack between the heterocyclic rings, due to intramolecular π–π interactions. The substituted ethyl and methyl groups are comparable as far as intramolecular stacking is concerned.     

Disappearance of intramolecular stacking due to one‐atom movement or increment of a `propyl­ene linker' in pyrazolo­[3,4‐d]­pyrimidine‐based ­flexible models

In the crystal structures of 4,6‐di­methyl­thio‐1‐[3‐(4,6‐di­methyl­thio‐2H‐pyra­zolo­[3,4‐d]­py­rimi­din‐2‐yl)­propyl]‐1H‐py­ra­­zolo­[3,4‐d]­py­rimi­dine, C₁₇H₂₀N₈S₄, and 1‐[4‐(4‐meth­oxy‐6‐methyl­thio‐1H‐pyra­zolo­[3,4‐d]py­rimi­din‐1‐yl)­butyl]‐5‐meth­yl‐6‐methyl­thio‐4,5‐di­hydro‐1H‐pyra­zolo­[3,4‐d]py­rimi­din‐4‐one, C₁₈H₂₂N₈O₂S₂, only intermolecular stacking due to aromatic π–π interactions between pyrazolo­[3,4‐d]­pyrimidinerings is present.     

Unusual molecular conformation in dissymmetric propyl­ene‐linker compounds containing pyrazolo­[3,4‐d]­pyrimidine and phthalimide moieties

The crystal structure of 4,6‐bis(methylsulfanyl)‐1‐phthalimidopropyl‐1H‐pyrazolo[3,4‐d]pyrimidine, C₁₈H₁₇N₅O₂S₂, (VI), reveals an unusual folded conformation due to an apparent intramolecular C—H⃛π interaction between the 6‐methyl­­sul­fanyl and phenyl groups. However, the closely related compound 6‐methyl­sulfanyl‐1‐phthalimido­propyl‐4‐(pyrroli­din‐1‐yl)‐1H‐pyrazolo­[3,4‐d]­pyrimidine, C₂₁H₂₂N₆O₂S, (VII), exhibits a fully extended structure, devoid of any intramol­ecular C—H⃛π or π–π interactions. The crystal packing of both mol­ecules involves intermolecular stacking interactions due to aromatic π–π interactions. In addition, (VI) exhibits intermolecular C—H⃛O hydrogen bonding and (VII) exhibits dimerization of the mol­ecules through intermolecular C—H⃛N hydrogen bonding.     

The regioisomeric 1H(2H)‐pyrazolo[3,4‐d]pyrimidine N1‐ and N2‐(2′‐deoxy‐β‐D‐ribofuranosides)

In the title regioisomeric nucleosides, alternatively called 1‐(2‐deoxy‐β‐d ‐erythro‐furan­osyl)‐1H‐pyrazolo­[3,4‐d]­pyrimidine, C₁₀H₁₂N₄O₃, (II), and 2‐(2‐deoxy‐β‐d ‐erythro‐furan­osyl)‐2H‐pyrazolo­[3,4‐d]pyrimidine, C₁₀H₁₂N₄O₃, (III), the conformations of the gly­cosyl­ic bonds are anti [?100.4 (2)° for (II) and 15.0 (2)° for (III)]. Both nucleosides adopt an S‐type sugar pucker, which is C2′‐endo‐C3′‐exo (²T₃) for (II) and 3′‐exo (between ₃E and ⁴T₃) for (III).     

A dimeric layered structure of a 4‐oxo‐4,5‐di­hydro‐1H‐pyrazolo­[3,4‐d]­pyrimidine compound

The title compound, 6‐methyl­sulfanyl‐1‐(3‐phenyl­propyl)‐4,5‐di­hydro‐1H‐pyrazolo­[3,4‐d]­pyrimidin‐4‐one, C₁₅H₁₆N₄OS, crystallizes in space group Pbca, with two mol­ecules of similar structure in the asymmetric unit. The molecular structure shows the absence of intramolecular stacking in the crystalline state, as indicated by earlier ¹H NMR analysis in solution. In addition, the crystal packing reveals the formation of a layered structure, due mainly to intermolecular N—H?O=C hydrogen bonding and arene–arene interactions.     

7‐Vinyl‐8‐aza‐7‐de­aza‐2′‐deoxy­adenosine monohydrate

In the title compound, 4‐amino‐1‐(2‐deoxy‐β‐d ‐eythro‐pento­furan­osyl)‐3‐vinyl‐1H‐pyrazolo­[3,4‐d]­pyrimidine monohydrate, C₁₂H₁₅N₅O₃·H₂O, the conformation of the gly­cosyl bond is anti. The furan­ose moiety is in an S conformation with an unsymmetrical twist, and the conformation at the exocyclic C—C(OH) bond is +sc (gauche, gauche). The vinyl side chain is bent out of the heterocyclic ring plane by 147.5 (5)°. The three‐dimensional packing is stabilized by O—H·O, O—H·N and N—H·O hydrogen bonds.     

A highly functionalized ferrocenyl­pyrazolo­[2,3‐a]­pyridine

The crystal structure of [2‐(4‐bromo­phenyl)‐4‐cyano‐5‐ferrocenyl­pyrazolo­[2,3‐a]­pyridin‐7‐yl]­aceto­nitrile, C₂₆H₁₇N₄FeBr or [Fe(C₅H₅)(C₂₁H₁₂BrN₄)], shows that the pyrazolo­pyridine ring system (PP), the bromo­phenyl ring (BP) and the cyclo­penta­diene ring (Cp) are nearly planar. The PP ring system is twisted out of the plane of the BP and Cp rings by about 20°.     

7‐Iodo‐8‐aza‐7‐deaza‐2′‐deoxy­adenosine and 7‐bromo‐8‐aza‐7‐deaza‐2′‐deoxyadenosine

The isomorphous structures of the title molecules, 4‐amino‐1‐(2‐deoxy‐β‐d ‐erythro‐pento­furan­osyl)‐3‐iodo‐1H‐pyrazolo‐[3,4‐d]pyrimidine, (I), C₁₀H₁₂IN₅O₃, and 4‐amino‐3‐bromo‐1‐(2‐deoxy‐β‐d ‐erythro‐pento­furan­osyl)‐1H‐pyrazolo[3,4‐d]­pyrimidine, (II), C₁₀H₁₂BrN₅O₃, have been determined. The sugar puckering of both compounds is C1′‐endo (^1′E). The N‐­glycosidic bond torsion angle χ¹ is in the high‐anti range [?73.2 (4)° for (I) and ?74.1 (4)° for (II)] and the crystal structure is stabilized by hydrogen bonds.     

Supramolecular hydrogen‐bonded hexamers in two 5‐aryl‐3‐methyl‐1‐phenyl‐1,6,7,8‐tetra­hydro­pyrazolo­[3,4‐b][1,4]­diazepines

In both title compounds, i.e. 3‐methyl‐1,5‐di­phenyl‐1,6,7,8‐tetra­hydro­pyrazolo­[3,4‐b][1,4]­diazepine, C₁₉H₁₈N₄, (I), and 5‐(4‐chloro­phenyl)‐3‐methyl‐1‐phenyl‐1,6,7,8‐tetra­hydro­pyra­zolo­[3,4‐b][1,4]­diazepine, C₁₉H₁₇ClN₄, (II), an N—H?N hydrogen bond links six mol­ecules to form an R(30) ring. Compound (I) crystallizes in the R space group and (II) crystallizes in P with three mol­ecules in the asymmetric unit. The mol­ecule of (I) contains a disordered seven‐membered ring.     

The molecular and supramolecular structures of the isomeric compounds 5,7‐di­methoxy­imidazo­[1,2‐c]­pyrimidine and 7‐methoxy‐1‐methyl­imidazo­[1,2‐a]­pyrimidin‐5(1H)‐one

The supramolecular structures of the isomeric compounds 5,7‐di­methoxy­imidazo­[1,2‐c]­pyrimidine, C₈H₉N₃O₂, (I), and 7‐methoxy‐1‐methyl­imidazo­[1,2‐a]­pyrimidin‐5(1H)‐one, C₈H₉N₃O₂, (II), are determined by weak C—H⃛N and C—H⃛O hydrogen bonds in (I), which generate alternating linked centrosymmetric R(8) and R(10) rings that form a ribbon running parallel to the c axis, and by C—H⃛O bonds in (II), which link the mol­ecules into sheets comprising centro­symmetric R(10) and R(22) rings.     

Rotenone α‐oxime

The structure determination of the title compound, rotenone α‐oxime [systematic name: 1,2,12,12a‐tetra­hydro‐8,9‐di­meth­oxy‐2‐(1‐methyl­ethenyl)‐[1]­benzo­py­rano­[3,4‐b]­furo­[2,3‐h][1]benzo­pyran‐6(6H)‐one oxime], C₂₃H₂₃NO₆, confirms that the mol­ecule has an approximately V‐shaped structure. One of the rings has a typical cyclo­hexene‐like monoplanar conformation and the central ring adopts a 1,2‐diplanar conformation.     

The molecular and supramolecular structures of four 1,5,6,10b‐tetrahydropyrazolo[1,5‐c]quinazolines

The supramolecular structures of the title compounds, 2‐phenyl‐5‐p‐tolyl‐1,5,6,10b‐tetra­hydro­pyrazolo­[1,5‐c]quinazoline, C₂₃H₂₁N₃, (I), 5‐(4‐bromo­phenyl)‐2‐phenyl‐1,5,6,10b‐tetra­hydro­pyrazolo­[1,5‐c]­quinazoline, C₂₂H₁₈BrN₃, (II), 2‐(4‐chlorophenyl)‐5‐phenyl‐1,5,6,10b‐tetrahydropyrazolo[1,5‐c]quinazoline, C₂₂H₁₈ClN₃, (III), and 5‐(4‐bromo­phenyl)‐2‐(4‐chlorophenyl)‐1,5,6,10b‐tetrahydropyrazolo[1,5‐c]quinazoline, C₂₂H₁₇BrClN₃, (IV), are of two general types. Compounds (I), (II) and (III) form base‐paired dimers via N—H?N hydrogen bonds, where (I) and (II) are isomorphous, while in (IV), there are no conventional hydrogen bonds.     

An anthracene dimer with a fused 1,3‐dithiole ring at 193 K

The first butterfly‐shaped anthracene dimer including S atoms,8,9‐di­hydro‐3a,8[1′,2′]:9,13b[1′′,2′′]­di­benzeno­dibenzo­[3,4:7,8]cyclo­octa­[1,2‐d]‐1,3‐di­thiole, C₂₉H₂₀S₂, contains an exceptionally long Csp³—Csp³ bond of 1.672 (2) Å in the fused 1,3‐di­thiole ring. The length of the other bond bridging the anthracene moieties is 1.604 (3) Å.     

Three ginkgolide hydrates from Ginkgo biloba L.: ginkgolide A monohydrate,ginkgolide C sesquihydrate and ginkgolide J dihydrate,all determined at 120 K

A low‐temperature structure of ginkgolide A monohydrate, (1R,3S,3aS,4R,6aR,7aR,7bR,8S,10aS,11aS)‐3‐(1,1‐dimethylethyl)‐hexa­hydro‐4,7b‐di­hydroxy‐8‐methyl‐9H‐1,7a‐epoxymethano‐1H,6aH‐cyclo­penta­[c]­furo­[2,3‐b]­furo­[3′,2′:3,4]­cyclopenta­[1,2‐d]­furan‐5,9,12(4H)‐trione monohydrate, C₂₀H₂₄O₉·H₂O, obtained from Mo Kα data, is a factor of three more precise than the previous room‐temperature determination. A refinement of the ginkgolide A monohydrate structure with Cu Kα data has allowed the assignment of the absolute configuration of the series of compounds. Ginkgolide C sesquihydrate, (1S,2R,3S,3aS,4R,6aR,7aR,7bR,8S,10aS,11S,11aR)‐3‐(1,1‐di­methyl­ethyl)‐hexa­hydro‐2,4,7b,11‐tetrahydroxy‐8‐methyl‐9H‐1,7a‐epoxy­methano‐1H,6aH‐cyclopenta­[c]­furo­[2,3‐b]­furo­[3′,2′:3,4]­cyclo­penta­[1,2‐d]­furan‐5,9,12(4H)‐trione sesquihydrate, C₂₀H₂₄O₁₁·1.5H₂O, has two independent diterpene mol­ecules, both of which exhibit intramolecular hydrogen bonding between OH groups. Ginkgolide J dihydrate, (1S,2R,3S,3aS,4R,6aR,7aR,7bR,8S,10aS,11aS)‐3‐(1,1‐di­methyl­ethyl)‐hexa­hydro‐2,4,7b‐tri­hydroxy‐8‐methyl‐9H‐1,7a‐epoxy­methano‐1H,6aH‐cyclo­penta­[c]­furo­[2,3‐b]furo[3′,2′:3,4]­cyclo­penta­[1,2‐d]­furan‐5,9,12(4H)‐trione dihydrate, C₂₀H₂₄O₁₀·2H₂O, has the same basic skeleton as the other ginkgolides, with its three OH groups having the same configurations as those in ginkgolide C. The conformations of the six five‐membered rings are quite similar across ­ginkgolides A–C and J, except for the A and F rings of ginkgolide A.     

Three 5H‐indeno­[1,2‐c]­pyridazin‐5‐one derivatives,potent type‐B mono­amine oxidase inhibitors

The structures of three compounds, namely 7‐methoxy‐2‐[3‐(tri­fluoro­methyl)­phenyl]‐9H‐indeno­[1,2‐c]­pyridazin‐9‐one, C₁₉H₁₁F₃N₂O₂, (Id), 6‐methoxy‐2‐[3‐(tri­fluoro­methyl)­phenyl]‐9H‐indeno­[1,2‐c]­pyridazin‐9‐one, C₁₉H₁₁F₃N₂O₂, (IId), and 2‐methyl‐6‐(4,4,4‐tri­fluoro­butoxy)‐9H‐indeno­[1,2‐c]­pyridazin‐9‐one, C₁₆H₁₃F₃N₂O₂, (IIf), which are potent reversible type‐B mono­amine oxidase (MAO‐B) inhibitors, are presented and discussed. Compounds (Id) and (IId) crystallize in a nearly planar conformation. The crystal structures are stabilized by weak C—H⋯O hydrogen bonds. The packing is dominated by π–π stacking interactions between the heterocyclic central moieties of centrosymmetrically related mol­ecules. In compound (IIf), the tri­fluoro­ethyl termination is almost perpendicular to the plane of the ring.     

2‐Amino‐4‐(4‐pyridyl)­pyrimidine and the 1:1 adduct with 4‐amino­benzoic acid

The structure of the title compound, C₉H₈N₄, comprises non‐planar mol­ecules that associate via pyrimidine N—H?N dimer R(8) hydrogen‐bonding associations [N?N 3.1870 (17) Å] and form linear hydrogen‐bonded chains via a pyrimidine N—H?N(pyridyl) interaction [N?N 3.0295 (19) Å]. The dihedral angle between the two rings is 24.57 (5)°. The structure of the 1:1 adduct with 4‐amino­benzoic acid, C₉H₈N₄·C₇H₇NO₂, exhibits a hydrogen‐bond­ing network involving COOH?N(pyridyl) [O?N 2.6406 (17) Å], pyrimidine N—H?N [N?N 3.0737 (19) and 3.1755 (18) Å] and acid N—H?O interactions [N?O 3.0609 (17) and 2.981 (2) Å]. The dihedral angle between the two linked rings of the base is 38.49 (6)° and the carboxyl­ic acid group binds to the stronger base group in contrast to the (less basic) complementary hydrogen‐bonding site.     

N8‐(2′‐O‐Methyl­ribofuranos­yl)‐8‐aza‐7‐deaza­adenine monohydrate

In the title compound, 4‐amino‐2‐(2‐O‐methyl‐β‐d ‐ribofuranos­yl)‐2H‐pyrazolo[3,4‐d]pyrimidine monohydrate, C₁₁H₁₅N₅O₄·H₂O, the conformation of the N‐glycosylic bond is syn [χ = 20.1 (2)°]. The ribofuran­ose moiety shows a C3′‐endo (³T₂) sugar puckering (N‐type sugar), and the conformation at the exocyclic C4′—C5′ bond is −ap (trans). The nucleobases are stacked head‐to‐head. The three‐dimensional packing of the crystal structure is stabilized by hydrogen bonds between the 2′‐O‐methyl­ribonucleosides and the solvent mol­ecules.     

1,N6‐Etheno derivative of 7‐de­aza‐2,8‐di­aza­adenosine

In the tricyclic nucleoside 7‐(β‐d ‐ribo­furan­osyl)‐7H‐imidazo­[1,2‐c]­pyrazolo­[4,3‐e][1,2,3]­triazine, C₁₁H₁₂N₆O₄, the con­formation of the N‐gly­cosyl bond is intermediate between anti and high anti [χ = −103.5 (3)°]. The ribo­furan­ose moiety adopts a ₃T² sugar pucker (S‐type sugar) and the conformation at the exocyclic C—C bond is ap (gauche–trans). Molecules of the title compound form a three‐dimensional network via three medium–strong intermolecular hydrogen bonds (one O—H⋯N and two O—H⋯O bonds).