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 [pi]-[pi] interactions. The substituted ethyl and methyl groups are comparable as far as intramolecular stacking is concerned.

S1. Comment

Interactions between aromatic units play a significant role in chemistry (Hunter, 1994), biology and crystal engineering (Desiraju, 1995). While π-π stacking is, by consensus, an important non-covalent interaction in DNA and proteins, the nature of this interaction remains under debate (Guckian et al., 2000). The use of a `propylene linker' was first documented by Brown et al. (1968) for the promotion of intramolecular stacking. Recently, we have reported convenient syntheses (Avasthi et al., 1995, 1998) and X-ray studies (Biswas et al., 1995; Maulik et al., 1998, 2000) of four novel `propylene linker' compounds based on pyrazolo[3,4-d]pyrimidines as new flexible models for studying aromatic π-π interactions (APPI). One of these four compounds, 1,1'-(1,3-propanediyl)bis(5-methyl-6-methylthio- 4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one), (I), showed beautiful inter- and intramolecular stacking due to APPI (Maulik et al., 1998). Since the X-ray structure of (I) was unique (a U-motif) for the demonstration of inter- and intramolecular stacking, it was thought worthwhile to replace the N-methyl group of (I) with an N-ethyl group, to determine the robustness of the U-motif and its consequence on intermolecular stacking. In this communication, we report the X-ray structure of the newly synthesized compound, 1,1'-(1,3-propanediyl)bis(5-ethyl-6-methylthio-4,5-dihydro- 1H-pyrazolo[3,4-d]pyrimidin-4-one), (II) (Avasthi & Aswal, 2001). \sch

The conformation of (II) is shown in Fig. 1. The molecule is folded at the centre of the bridge [C10—C11—C12 114.9 (2)°], due to intramolecular APPI between the pyrazolo[3,4-d]pyrimidine rings. For comparison, the corresponding angle in (I) is 115.2 (2)°. In compound (II), as in (I), the two pyrazolo[3,4-d]pyrimidine rings are positioned in such a way that only a part of the pyrimidinyl rings overlap (Fig. 1). The overlapping six-membered rings are separated by an average distance of 3.415 (3) Å [3.37 (1) Å in (I)], thus confirming the presence of intramolecular APPI.

The pyrazolo[3,4-d]pyrimidine rings of (II) are nearly planar [maximum deviation -0.062 (2) Å] and the angle between the least-squares planes is 12.5 (1)° [12.4 (5)° in (I)]. The packing diagram (Fig. 2) shows that the molecules are stacked in the a direction in such a way that similar sides of the U-motif are adjacent to each other. The approximate intermolecular spacing between adjacent rings are 3.7 and 4.0 Å in (I) and (II)?, respectively.

In conclusion, replacement of the N-methyl group in (I) with an N-ethyl group in (II) has not produced any significant change in the U-motif produced by intramolecular stacking due to APPI. However, the intermolecular packing pattern has changed, due to the presence of the bulky ethyl group.

Related literature

For related literature, see: Avasthi & Aswal (2001); Avasthi et al. (1995, 1998); Biswas et al. (1995); Brown et al. (1968); Desiraju (1995); Guckian et al. (2000); Hunter (1994); Maulik et al. (1998, 2000).

S2. Experimental

Compound (II) was synthesized using a method similar to that described earlier by Avathi et al. (1998) for the synthesis of (I), except that ethyl iodide was used in place of methyl iodide. Diffraction quality crystals of (II) were obtained by slow evaporation of an ethyl acetate solution at room temperature.

S3. Refinement

All H atoms were placed in geometrical idealized positions and allowed to ride on their parent atoms, to which each was bonded for the final cycles of refinement.

Computing details

Data collection: XSCANS (Siemens, 1996); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXTL (Bruker, 1997); program(s) used to refine structure: SHELXTL; molecular graphics: NRCVAX (Gabe et al., 1989), ORTEP (Johnson, 1965) and PLUTO (Motherwell & Clegg, 1978); software used to prepare material for publication: SHELXTL.

Figures

	Fig. 1. The molecular view of (II), showing the intramolecular stacking and with displacement ellipsoids at the 30% probability level. H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. A stereo-view crystal packing diagram for (II).

1,1'-(1,3-propanediyl)bis(5-ethyl-6-methylthio-4,5-dihydro-1H- pyrazolo[3,4-d]pyrimidin-4-one)

Crystal data

C19H24N8O2S2	Dx = 1.405 Mg m^−3
Mr = 460.58	Melting point = 114–115 K
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 31.385 (2) Å	Cell parameters from 58 reflections
b = 9.129 (1) Å	θ = 4.7–12.5°
c = 16.840 (1) Å	µ = 0.28 mm^−1
β = 115.52°	T = 293 K
V = 4354.1 (6) Å^3	Block, colourless
Z = 8	0.43 × 0.36 × 0.33 mm
F(000) = 1936

Data collection

Bruker P4 diffractometer	Rint = 0.013
Radiation source: fine-focus sealed tube	θmax = 25.0°, θmin = 2.3°
Graphite monochromator	h = −1→37
θ/2θ scans	k = −1→10
4602 measured reflections	l = −20→18
3826 independent reflections	3 standard reflections every 97 reflections
3276 reflections with I > 2σ(I)	intensity decay: none

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.036	H-atom parameters constrained
wR(F^2) = 0.097	w = 1/[σ^2(Fo^2) + (0.0401P)^2 + 3.2946P] where P = (Fo^2 + 2Fc^2)/3
S = 1.05	(Δ/σ)max = 0.001
3826 reflections	Δρmax = 0.20 e Å^−3
285 parameters	Δρmin = −0.30 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.00100 (11)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
S1	0.210035 (19)	0.42208 (5)	1.01895 (4)	0.05631 (16)
S2	0.06944 (2)	0.63711 (7)	1.01316 (3)	0.06336 (18)
N20	0.06343 (5)	0.75940 (15)	0.86778 (9)	0.0404 (3)
N8	0.18618 (5)	0.69436 (16)	0.96278 (10)	0.0427 (3)
N18	0.07007 (5)	0.49951 (16)	0.87362 (10)	0.0473 (4)
N13	0.06061 (5)	0.85729 (16)	0.73377 (9)	0.0434 (3)
N1	0.16480 (5)	0.94652 (16)	0.92307 (11)	0.0485 (4)
N6	0.20406 (5)	0.64687 (17)	1.11352 (10)	0.0465 (4)
C21	0.06154 (6)	0.74506 (18)	0.78597 (11)	0.0382 (4)
N2	0.16039 (6)	1.07329 (18)	0.96264 (13)	0.0614 (5)
C9	0.17814 (6)	0.83494 (19)	0.98102 (12)	0.0424 (4)
C7	0.19886 (6)	0.60753 (19)	1.03065 (12)	0.0424 (4)
C19	0.06721 (6)	0.6351 (2)	0.90731 (12)	0.0430 (4)
O2	0.06830 (6)	0.35912 (16)	0.75944 (11)	0.0711 (4)
C16	0.06045 (6)	0.6168 (2)	0.74183 (12)	0.0443 (4)
C17	0.06584 (6)	0.4816 (2)	0.78643 (13)	0.0489 (4)
N14	0.05931 (6)	0.8078 (2)	0.65575 (10)	0.0544 (4)
C26	0.20015 (8)	0.4161 (2)	0.90658 (14)	0.0610 (5)
H26A	0.1683	0.4458	0.8698	0.091*
H26B	0.2050	0.3180	0.8916	0.091*
H26C	0.2218	0.4812	0.8978	0.091*
C4	0.18172 (6)	0.8875 (2)	1.06053 (13)	0.0485 (4)
C15	0.05866 (7)	0.6642 (2)	0.66083 (13)	0.0549 (5)
H15	0.0572	0.6013	0.6162	0.066*
O1	0.19828 (5)	0.81961 (19)	1.20709 (9)	0.0683 (4)
C10	0.15988 (7)	0.9474 (2)	0.83320 (14)	0.0530 (5)
H10A	0.1534	0.8484	0.8101	0.064*
H10B	0.1897	0.9775	0.8338	0.064*
C12	0.07180 (7)	1.00907 (19)	0.76000 (13)	0.0479 (4)
H12A	0.0694	1.0257	0.8149	0.057*
H12B	0.0491	1.0722	0.7156	0.057*
C5	0.19458 (6)	0.7912 (2)	1.13355 (13)	0.0500 (5)
C22	0.21874 (7)	0.5397 (2)	1.18633 (13)	0.0574 (5)
H22A	0.2363	0.5905	1.2415	0.069*
H22B	0.2398	0.4687	1.1791	0.069*
C27	0.05863 (8)	0.8254 (3)	1.02475 (15)	0.0685 (6)
H27A	0.0833	0.8838	1.0215	0.103*
H27B	0.0580	0.8407	1.0806	0.103*
H27C	0.0288	0.8534	0.9784	0.103*
C3	0.17012 (8)	1.0369 (2)	1.04412 (15)	0.0595 (5)
H3	0.1694	1.1021	1.0860	0.071*
C11	0.12118 (7)	1.0478 (2)	0.77175 (14)	0.0539 (5)
H11A	0.1282	1.1472	0.7941	0.065*
H11B	0.1216	1.0462	0.7145	0.065*
C24	0.07922 (7)	0.3647 (2)	0.92724 (16)	0.0615 (6)
H24A	0.0966	0.3901	0.9889	0.074*
H24B	0.0988	0.2994	0.9118	0.074*
C23	0.17781 (9)	0.4597 (3)	1.19114 (15)	0.0729 (7)
H23A	0.1576	0.5288	1.2013	0.109*
H23B	0.1896	0.3902	1.2385	0.109*
H23C	0.1602	0.4093	1.1367	0.109*
C25	0.03473 (9)	0.2859 (3)	0.91449 (19)	0.0768 (7)
H25A	0.0154	0.3493	0.9308	0.115*
H25B	0.0426	0.1998	0.9507	0.115*
H25C	0.0178	0.2583	0.8538	0.115*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0630 (3)	0.0377 (3)	0.0622 (3)	0.0088 (2)	0.0213 (3)	0.0037 (2)
S2	0.0709 (4)	0.0714 (4)	0.0494 (3)	−0.0061 (3)	0.0275 (3)	0.0093 (3)
N20	0.0434 (8)	0.0358 (8)	0.0439 (8)	−0.0023 (6)	0.0205 (7)	−0.0009 (6)
N8	0.0402 (8)	0.0355 (8)	0.0486 (8)	0.0007 (6)	0.0156 (6)	−0.0014 (7)
N18	0.0443 (8)	0.0366 (8)	0.0566 (9)	−0.0008 (6)	0.0175 (7)	0.0045 (7)
N13	0.0483 (8)	0.0411 (8)	0.0423 (8)	0.0000 (6)	0.0209 (7)	0.0003 (6)
N1	0.0478 (8)	0.0340 (8)	0.0602 (10)	0.0009 (6)	0.0199 (7)	0.0008 (7)
N6	0.0402 (8)	0.0470 (9)	0.0445 (8)	0.0002 (7)	0.0109 (6)	−0.0009 (7)
C21	0.0349 (8)	0.0357 (9)	0.0445 (9)	−0.0006 (7)	0.0176 (7)	−0.0018 (7)
N2	0.0660 (11)	0.0346 (9)	0.0794 (13)	0.0022 (8)	0.0272 (10)	−0.0045 (8)
C9	0.0349 (8)	0.0345 (9)	0.0537 (10)	−0.0028 (7)	0.0152 (8)	−0.0022 (8)
C7	0.0336 (8)	0.0378 (9)	0.0507 (10)	−0.0007 (7)	0.0133 (7)	−0.0010 (8)
C19	0.0364 (9)	0.0444 (10)	0.0467 (10)	−0.0039 (7)	0.0164 (7)	0.0004 (8)
O2	0.0816 (11)	0.0380 (8)	0.0861 (11)	0.0044 (7)	0.0287 (9)	−0.0137 (7)
C16	0.0432 (9)	0.0401 (10)	0.0482 (10)	−0.0004 (7)	0.0184 (8)	−0.0064 (8)
C17	0.0423 (10)	0.0371 (10)	0.0622 (12)	−0.0006 (8)	0.0179 (9)	−0.0072 (9)
N14	0.0632 (10)	0.0589 (11)	0.0444 (9)	0.0011 (8)	0.0263 (8)	−0.0008 (8)
C26	0.0637 (13)	0.0482 (12)	0.0705 (13)	0.0043 (10)	0.0285 (11)	−0.0085 (10)
C4	0.0423 (9)	0.0422 (10)	0.0560 (11)	−0.0036 (8)	0.0164 (8)	−0.0087 (9)
C15	0.0610 (12)	0.0574 (13)	0.0477 (11)	0.0020 (10)	0.0247 (9)	−0.0113 (9)
O1	0.0727 (10)	0.0742 (11)	0.0517 (8)	−0.0044 (8)	0.0207 (7)	−0.0171 (8)
C10	0.0494 (11)	0.0470 (11)	0.0646 (12)	0.0017 (9)	0.0265 (9)	0.0073 (9)
C12	0.0542 (11)	0.0338 (9)	0.0564 (11)	0.0056 (8)	0.0245 (9)	0.0071 (8)
C5	0.0408 (9)	0.0511 (11)	0.0524 (11)	−0.0066 (8)	0.0147 (8)	−0.0114 (9)
C22	0.0527 (11)	0.0618 (13)	0.0463 (10)	0.0038 (10)	0.0106 (9)	0.0070 (9)
C27	0.0724 (14)	0.0846 (17)	0.0574 (12)	−0.0192 (13)	0.0364 (11)	−0.0222 (12)
C3	0.0629 (13)	0.0403 (11)	0.0714 (14)	−0.0007 (9)	0.0253 (11)	−0.0129 (10)
C11	0.0592 (12)	0.0387 (10)	0.0652 (12)	0.0001 (9)	0.0282 (10)	0.0134 (9)
C24	0.0529 (12)	0.0451 (11)	0.0767 (14)	0.0030 (9)	0.0188 (10)	0.0166 (10)
C23	0.0743 (15)	0.0844 (17)	0.0566 (13)	−0.0067 (13)	0.0251 (11)	0.0161 (12)
C25	0.0704 (15)	0.0618 (14)	0.0960 (18)	−0.0121 (12)	0.0337 (13)	0.0172 (13)

Geometric parameters (Å, º)

S1—C7	1.7571 (18)	C26—H26C	0.9600
S1—C26	1.782 (2)	C4—C3	1.408 (3)
S2—C19	1.7536 (19)	C4—C5	1.421 (3)
S2—C27	1.779 (3)	C15—H15	0.9300
N20—C19	1.295 (2)	O1—C5	1.221 (2)
N20—C21	1.359 (2)	C10—C11	1.517 (3)
N8—C7	1.304 (2)	C10—H10A	0.9700
N8—C9	1.368 (2)	C10—H10B	0.9700
N18—C19	1.381 (2)	C12—C11	1.517 (3)
N18—C17	1.426 (3)	C12—H12A	0.9700
N18—C24	1.479 (2)	C12—H12B	0.9700
N13—C21	1.342 (2)	C22—C23	1.510 (3)
N13—N14	1.373 (2)	C22—H22A	0.9700
N13—C12	1.451 (2)	C22—H22B	0.9700
N1—C9	1.347 (2)	C27—H27A	0.9600
N1—N2	1.372 (2)	C27—H27B	0.9600
N1—C10	1.454 (2)	C27—H27C	0.9600
N6—C7	1.381 (2)	C3—H3	0.9300
N6—C5	1.423 (2)	C11—H11A	0.9700
N6—C22	1.478 (2)	C11—H11B	0.9700
C21—C16	1.380 (2)	C24—C25	1.501 (3)
N2—C3	1.313 (3)	C24—H24A	0.9700
C9—C4	1.380 (3)	C24—H24B	0.9700
O2—C17	1.221 (2)	C23—H23A	0.9600
C16—C15	1.409 (3)	C23—H23B	0.9600
C16—C17	1.417 (3)	C23—H23C	0.9600
N14—C15	1.315 (3)	C25—H25A	0.9600
C26—H26A	0.9600	C25—H25B	0.9600
C26—H26B	0.9600	C25—H25C	0.9600
C7—S1—C26	101.35 (9)	N1—C10—H10B	108.7
C19—S2—C27	101.28 (10)	C11—C10—H10B	108.7
C19—N20—C21	113.02 (15)	H10A—C10—H10B	107.6
C7—N8—C9	112.93 (16)	N13—C12—C11	111.23 (15)
C19—N18—C17	122.18 (15)	N13—C12—H12A	109.4
C19—N18—C24	121.66 (17)	C11—C12—H12A	109.4
C17—N18—C24	116.13 (16)	N13—C12—H12B	109.4
C21—N13—N14	111.02 (15)	C11—C12—H12B	109.4
C21—N13—C12	126.55 (15)	H12A—C12—H12B	108.0
N14—N13—C12	120.61 (15)	O1—C5—C4	127.9 (2)
C9—N1—N2	110.55 (16)	O1—C5—N6	119.93 (19)
C9—N1—C10	128.27 (16)	C4—C5—N6	112.22 (17)
N2—N1—C10	120.87 (16)	N6—C22—C23	113.33 (16)
C7—N6—C5	122.32 (16)	N6—C22—H22A	108.9
C7—N6—C22	121.67 (16)	C23—C22—H22A	108.9
C5—N6—C22	116.00 (16)	N6—C22—H22B	108.9
N13—C21—N20	124.71 (15)	C23—C22—H22B	108.9
N13—C21—C16	107.86 (15)	H22A—C22—H22B	107.7
N20—C21—C16	127.43 (16)	S2—C27—H27A	109.5
C3—N2—N1	105.50 (16)	S2—C27—H27B	109.5
N1—C9—N8	125.22 (17)	H27A—C27—H27B	109.5
N1—C9—C4	108.05 (16)	S2—C27—H27C	109.5
N8—C9—C4	126.73 (17)	H27A—C27—H27C	109.5
N8—C7—N6	125.88 (17)	H27B—C27—H27C	109.5
N8—C7—S1	119.19 (14)	N2—C3—C4	111.97 (19)
N6—C7—S1	114.93 (13)	N2—C3—H3	124.0
N20—C19—N18	125.60 (16)	C4—C3—H3	124.0
N20—C19—S2	117.92 (14)	C12—C11—C10	114.87 (16)
N18—C19—S2	116.47 (13)	C12—C11—H11A	108.6
C21—C16—C15	104.02 (17)	C10—C11—H11A	108.6
C21—C16—C17	118.98 (17)	C12—C11—H11B	108.6
C15—C16—C17	136.61 (18)	C10—C11—H11B	108.6
O2—C17—C16	127.8 (2)	H11A—C11—H11B	107.5
O2—C17—N18	119.72 (18)	N18—C24—C25	112.78 (17)
C16—C17—N18	112.50 (15)	N18—C24—H24A	109.0
C15—N14—N13	105.13 (16)	C25—C24—H24A	109.0
S1—C26—H26A	109.5	N18—C24—H24B	109.0
S1—C26—H26B	109.5	C25—C24—H24B	109.0
H26A—C26—H26B	109.5	H24A—C24—H24B	107.8
S1—C26—H26C	109.5	C22—C23—H23A	109.5
H26A—C26—H26C	109.5	C22—C23—H23B	109.5
H26B—C26—H26C	109.5	H23A—C23—H23B	109.5
C9—C4—C3	103.91 (18)	C22—C23—H23C	109.5
C9—C4—C5	119.87 (17)	H23A—C23—H23C	109.5
C3—C4—C5	136.2 (2)	H23B—C23—H23C	109.5
N14—C15—C16	111.96 (17)	C24—C25—H25A	109.5
N14—C15—H15	124.0	C24—C25—H25B	109.5
C16—C15—H15	124.0	H25A—C25—H25B	109.5
N1—C10—C11	114.10 (16)	C24—C25—H25C	109.5
N1—C10—H10A	108.7	H25A—C25—H25C	109.5
C11—C10—H10A	108.7	H25B—C25—H25C	109.5