Disappearance of intramolecular stacking due to one-atom movement or increment of a `propylene linker' in pyrazolo[3,4-d]pyrimidine-based flexible models Prakas R. Maulik, a * Kamlakar Avasthi, b Sanjay Sarkhel, a Tilak Chandra, b Diwan S. Rawat, b Brad Logsdon c and Robert A. Jacobson c a Membrane Biology Division, Central Drug Research Institute, Lucknow 226 001, India, b Medicinal Chemistry Division, Central Drug Research Institute, Lucknow 226 001, India, and c Department of Chemistry, Iowa State University, Ames, Iowa 50011-3111, USA Correspondence e-mail: root@cscdri.ren.nic.in Received 2 June 2000 Accepted 31 July 2000 In the crystal structures of 4,6-dimethylthio-1-[3-(4,6-di- methylthio-2H-pyrazolo[3,4-d]pyrimidin-2-yl)propyl]-1H-py- razolo[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-meth- yl-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 ± interactions between pyrazolo[3,4-d]pyrimidine rings is present. Comment Interactions between aromatic units play a signi®cant role in chemistry and biology. The use of a `propylene linker' was ®rst documented by Brown et al. (1968) for the promotion of intramolecular aromatic ± interactions (APPI). Recently, we have reported convenient synthesis, high resolution 1 H NMR analysis (Avasthi et al., 1995; Avasthi, Rawat, Chandra & Bhakuni, 1998) and X-ray studies (Biswas et al. , 1995; Maulik et al., 1998) of three novel `propylene linker' compounds: 1,3-bis(4,6-dimethylthio-1H-pyrazolo[3,4-d]py- rimidin-1-yl)propane, (1), 1,1 0 -(1,3-propanediyl)bis(5-methyl- 6-methylthio-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one, (2), and 1-[3-(4-methoxy-6-methylthio-1H-pyrazolo[3,4-d]- pyrimidin-1-yl)propyl]-5-methyl-6-methylthio-4,5-dihydro-1H- pyrazolo[3,4-d]pyrimidin-4-one, (3). These three compounds show inter/intramolecular stacking due to APPI. In this communication, we report the crystal structures of two compounds, (4) and (5), which are very closely related to our earlier ¯exible models (1)±(3). 4,6-Dimethylthio-1-[3-(4,6-dimethylthio-2H-pyrazolo[3,4-d]- pyrimidin-2-yl)propyl]-1H-pyrazolo[3,4-d]pyrimidine, (4), was prepared earlier as a co-product during the synthesis of (1). The conformation of (4) is shown in Fig. 1. The structure does not show any intramolecular stacking [N1 0 ÐN2 3.956 (3) A Ê ], although the angle at the centre of the bridge [C8ÐC9ÐC10 114.9 (3)  ] is quite comparable to the corresponding angle in the structure of (1) (Biswas et al. , 1995). This disappearance of intramolecular stacking compared with the structure of (1) may highlight the importance of speci®c orientation for intramolecular stacking (Hobza & Sponer, 1999). Interest- ingly, intermolecular stacking due to APPI is still present (Fig. 2), as indicated by an average space of 3.67 (4) A Ê between two stacked rings [angle between the stacked rings: 6.32 (10)  ]. The other compound, 1-[4-(4-methoxy-6-methyl- thio-1H-pyrazolo[3,4- d]pyrimidin-1-yl)butyl]-5-methyl-6- methylthio-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one, (5), which differs from compound (3) in having an extra methylene group in its linker, has been synthesized by us recently (Avasthi, Rawat, Chandra & Bhakuni, 1998). The conformation of (5) is shown in Fig. 3. Once again, the crystal structure does not show any intramolecular stacking [N1ÐN1 0 5.249 (2) A Ê and torsion angle C8ÐC9ÐC10ÐC11 170.3 (2)  ] con®rming an earlier conclusion drawn on the basis of 1 H Acta Cryst. (2000). C56, 1361±1363 # 2000 International Union of Crystallography  Printed in Great Britain ± all rights reserved 1361 organic compounds Acta Crystallographica Section C Crystal Structure Communications ISSN 0108-2701 Figure 1 ORTEP (Johnson, 1965) diagram showing the molecular structure of (4) with labelling of the non-H atoms and displacement ellipsoids at the 50% probability level.