Kamlakar Avasthi

1H NMR and X-ray crystallographic analysis of 1,2-bis(4,6-diethylthio-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethane and its ‘propylene linker’-analog: molecular recognition versus crystal engineering ☆

Abstract Proton NMR analysis on newly synthesized 1,2-bis(4,6-diethylthio-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethane, 2c , and 1,2-bis(4,6-diethylthio-1H-pyrazolo[3,4-d]pyrimidin-1-yl)propane, 2d , showed intramolecular stacking in solution. X-Ray crystallography on 2c and 2d , however, confirmed the presence of such intramolecular stacking only in case of the ‘propylene linker’ compound, 2d , while the ‘ethylene linker’ compound, 2c , was devoid of it.

An alternative to ‘propylene/Leonard linker’ for studying arene interactions in flexible pyrazolo[3,4-d]pyrimidine core based models both at molecular and supramolecular levels

An alternative C-3 linker to ‘propylene/Leonard linker’ is proposed for studying arene interactions in face-to-face (offset) mode. The two new flexible symmetrical compounds with an electron deficient pyrazolo[3,4-d]pyrimidine core and biologically important isomeric purine systems and one dissymmetrical compound with a pyrazolo[3,4-d]pyrimidine core and electron-rich carbazole residue at the termini of the new linker show folding due to intramolecular π–π interactions by both 1H NMR in solution and X-ray crystallography in the solid state. Surprisingly, the replacement of the 4-methylsulfanyl group of the dissymmetrical compound by an electron donating methoxy group shows open conformation in the solid state by X-ray crystallography. The fifth symmetrical compound with an electron-rich carbazole residue at the termini of new linker, however, shows the normally expected open conformation.

Role of arene interactions and substituent effects in conformational (syn/anti) control of 1,2-diarylethanes

Conformational analysis of nine designed flexible 1,2-diarylethanes with different substituents show syn conformation due to π–π interactions by 1H NMR in solution, this carries over to the solid state for three compounds while two show anti conformation in the solid state by X-ray crystallography and the remaining compounds do not give diffraction quality crystals.

Pyrazolo[3,4-d]pyrimidinophanes: convenient synthesis of a new class of cyclophane and X-ray structure of the first representative.

A convenient synthesis of a new class of novel pyrazolo[3,4-d]pyrimidinophanes (four products, 41%), a new class of cyclophane, and X-ray structure of the first dissymmetrical [3.4]pyrazolo[3,4-d]pyrimidinophane (22%) are reported for the first time. The conformation of major syn product 6b is stabilized by weak pi-pi and O...Ar interactions.

1,3‐Bis[4,6‐bis(methylthio)‐1H‐pyrazolo[3,4‐d]pyrimidin‐1‐yl]propane

In the crystal structure of 1,3-bis[4,6-bis(methylthio)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]propane, C l7 H 20 N 8 S 4 , the molecules exhibit a skewed mode of stacking of the two pyrazolo[3,4-d]pyrimidine rings due to an intramolecular π-π interaction between the heterocyclic rings.

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

In the crystal structure of 1,3-bis(4,6-diisopropylsulfanyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)propane, C(25)H(36)N(8)S(4), the pairs of pyrazolo[3,4-d]pyrimidine rings in the molecule stack as a result of intramolecular pi-pi interactions between the heterocyclic rings. The crystal packing also exhibits an intermolecular C--H...pi interaction between one methyl group of an isopropyl group and a pyrazolo[3,4-d]pyrimidine ring.

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, C(18)H(17)N(5)O(2)S(2), (VI), reveals an unusual folded conformation due to an apparent intramolecular C-H.pi 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, C(21)H(22)N(6)O(2)S, (VII), exhibits a fully extended structure, devoid of any intramolecular C-H.pi or pi-pi interactions. The crystal packing of both molecules involves intermolecular stacking interactions due to aromatic pi-pi interactions. In addition, (VI) exhibits intermolecular C-H.O hydrogen bonding and (VII) exhibits dimerization of the molecules through intermolecular C-H.N hydrogen bonding.

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, C(22)H(29)N(9)S(3), 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, C(25)H(34)N(10)S(2), which differ in having either a pyrrolidine substituent or a methylsulfanyl group, show intermolecular stacking due to aromatic pi-pi interactions between the pyrazolo[3,4-d]pyrimidine rings.

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, C(17)H(20)N(8)S(4), 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, C(18)H(22)N(8)O(2)S(2), only intermolecular stacking due to aromatic pi-pi interactions between pyrazolo[3,4-d]pyrimidinerings is present.

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, C(15)H(16)N(4)OS, 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 (1)H NMR analysis in solution. In addition, the crystal packing reveals the formation of a layered structure, due mainly to intermolecular N[bond]H...O[double bond]C hydrogen bonding and arene-arene interactions.