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Acta Crystallogr Sect E Struct Rep Online. 2009 August 1; 65(Pt 8): o1720–o1721.
Published online 2009 July 1. doi:  10.1107/S1600536809023952
PMCID: PMC2977168

4-Hydrazino-1-methyl­pyrazolo[3,4-d]pyrimidine

Abstract

The title compound, C6H8N6, crystallizes as an N—H(...)N hydrogen-bond-linked dimer of two almost identical mol­ecules in the asymmetric unit. Both of the mol­ecules are almost planar (rms deviations of 0.0186 and 0.0296 Å in the two molecules) and their hydrazino groups are turned towards the pyrazole rings. The dimers are arranged into chains via inter­molecular N—H(...)N hydrogen bonds between the hydrazino groups and the N atoms of the pyrimidine rings of both types of the mol­ecules, linking the mol­ecules into a C(7) graph-set motif along [100]. The methyl groups and the N atoms of the pyrazole rings form weak C—H(...)N hydrogen bonds, which connect chains of the dimers in a C(4) motif parallel to [100].

Related literature

For recent reviews on the synthesis and biological activity of pyrazolo[3,4-d]pyrimidines, see: Caravatti et al. (2001 [triangle]); Dang (2002 [triangle]); Schenone et al. (2007 [triangle]); Schenone et al. (2008 [triangle]). The synthesis of the title compound was performed according to the procedure reported by Taylor & Loeffler (1960 [triangle]). For the crystal structure of 1-methyl-4-(2-methyl­hydrazino)pyrazolo[3,4-d]pyrimidine, see: Hosmane et al. (1988 [triangle]). For the graph-set analysis of hydrogen bonding, see: Bernstein et al. (1995 [triangle]).

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Object name is e-65-o1720-scheme1.jpg

Experimental

Crystal data

  • C6H8N6
  • M r = 164.18
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-65-o1720-efi1.jpg
  • a = 14.086 (4) Å
  • b = 3.8756 (12) Å
  • c = 27.271 (8) Å
  • V = 1488.8 (8) Å3
  • Z = 8
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 223 K
  • 0.58 × 0.26 × 0.10 mm

Data collection

  • Bruker SMART APEX CCD diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 2001 [triangle]) T min = 0.943, T max = 0.990
  • 8939 measured reflections
  • 1715 independent reflections
  • 1652 reflections with I > 2σ(I)
  • R int = 0.051

Refinement

  • R[F 2 > 2σ(F 2)] = 0.065
  • wR(F 2) = 0.159
  • S = 1.21
  • 1715 reflections
  • 243 parameters
  • 1 restraint
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.29 e Å−3
  • Δρmin = −0.28 e Å−3

Data collection: SMART (Bruker, 2001 [triangle]); cell refinement: SAINT (Bruker, 2001 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809023952/jh2082sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809023952/jh2082Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

This work was supported by the National Medical Research Council, Singapore (NMRC/NIG/0020/2008) and the National University of Singapore (R-148–050-091–101/133).

supplementary crystallographic information

Comment

The pyrazolo[3,4-d]pyrimidine heterocyclic system is known to be a bioisoster of purine. Therefore, chemistry of pyrazolo[3,4-d]pyrimidines has received significant attention, particularly for the development of new biologically active substances (Caravatti et al., 2001; Dang, 2002; Schenone et al., 2007; Schenone et al., 2008).

Herein, we report the crystal structure of 4-hydrazino-1-methylpyrazolo[3,4-d]pyrimidine, which was prepared via a reaction of 4-cyano-5-[(ethoxymethylene)amino]-1-methylpyrazole with hydrazine according to Taylor and Loeffler (1960) (Fig. 1). Theoretically, the compound might be involved in tautomerism with three tautomeric forms (Fig. 2). However, only one tautomeric form, similarly to previously reported 1-methyl-4-(2-methylhydrazino)pyrazolo[3,4-d]pyrimidine (Hosmane et al., 1988), was found in the crystal.

The title compound crystallizes in asymmetric unit as a dimer of two almost identical molecules (Fig. 3). Both molecules are essentially planar except for the hydrazino groups, which are turned towards pyrazole ring making the torsion angles C2—C5—N5—N6 and C8—C11—N11—N12 equal to 4.1 (7)° and 4.0 (7)°, respectively. The geometry of the molecule as well as 1.348 (6) Å and 1.332 (5) Å distances of C5—N5 and C11—N11 bonds indicate delocalization of the electron pairs of N5 and N11 with the pyrazolo[3,4-d]pyrimidine aromatic system.

In the crystal, the dimer molecules are linked in a R22(8) graph-set motif (Bernstein et al., 1995) by the N—H···N hydrogen bonds (Fig. 4, Table 1). The dimers are arranged into chains via intermolecular N—H···N hydrogen bonds between the hydrazino groups and the nitrogen atoms of the pyrimidine rings of both type of the molecules linking them with symmetry-related molecules in a C(7) graph-set motif along the [100] direction. The interactions between pyrimidine rings and hydrazino groups make a R44(14) hydrogen bond motif of the fourth order. The methyl groups and the nitrogen atoms of the pyrazole rings form weak C—H···N hydrogen bonds connecting chains of the dimers in a C(4) motif parallel to the [100]) direction.

Experimental

4-Hydrazino-1-methylpyrazolo[3,4-d]pyrimidine was synthesized by cyclocondensation of 4-cyano-5-[(ethoxymethylene)amino]-1-methylpyrazole with hydrazine according to the procedure reported by Taylor and Loeffler (1960). Single crystals suitable for crystallographic analysis were grown by recrystallization from ethanol.

Refinement

All the H atoms attached to the carbon atoms were constrained in a riding motion approximation [0.94 Å for Caryl—H and 0.97 Å for methyl groups; Uiso(H) =1.2Ueq(Caryl) and Uiso(H) =1.5Ueq(Cmethyl)] while the N-bound H atoms were located in a difference map and refined freely. Friedel pairs were merged.

Figures

Fig. 1.
The synthesis of 4-hydrazino-1-methylpyrazolo[3,4-d]pyrimidine
Fig. 2.
The hydrazino-hydrazono tautomerism in the title compound
Fig. 3.
The molecular structure of 4-hydrazino-1-methylpyrazolo[3,4-d]pyrimidine with the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
Fig. 4.
Molecular parking in the crystal, viewed along the b axis.

Crystal data

C6H8N6Dx = 1.465 Mg m3
Mr = 164.18Melting point: 514 K
Orthorhombic, Pna21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2nCell parameters from 3657 reflections
a = 14.086 (4) Åθ = 2.9–27.2°
b = 3.8756 (12) ŵ = 0.10 mm1
c = 27.271 (8) ÅT = 223 K
V = 1488.8 (8) Å3Block, colourless
Z = 80.58 × 0.26 × 0.10 mm
F(000) = 688

Data collection

Bruker SMART APEX CCD diffractometer1715 independent reflections
Radiation source: fine-focus sealed tube1652 reflections with I > 2σ(I)
graphiteRint = 0.051
[var phi] and ω scansθmax = 27.5°, θmin = 1.5°
Absorption correction: multi-scan (SADABS; Sheldrick, 2001)h = −18→18
Tmin = 0.943, Tmax = 0.990k = −5→4
8939 measured reflectionsl = −24→35

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.065Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.159H atoms treated by a mixture of independent and constrained refinement
S = 1.21w = 1/[σ2(Fo2) + (0.0699P)2 + 1.3392P] where P = (Fo2 + 2Fc2)/3
1715 reflections(Δ/σ)max < 0.001
243 parametersΔρmax = 0.29 e Å3
1 restraintΔρmin = −0.28 e Å3

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 (Å2)

xyzUiso*/Ueq
N10.4891 (3)0.4783 (12)0.43889 (16)0.0351 (9)
N20.4203 (3)0.6408 (11)0.46578 (15)0.0307 (9)
N30.3922 (2)0.8124 (10)0.54938 (15)0.0273 (9)
N40.5189 (3)0.6416 (10)0.60298 (15)0.0281 (8)
N50.6553 (3)0.3740 (12)0.57903 (17)0.0321 (9)
H5N0.668 (4)0.343 (14)0.609 (2)0.030 (14)*
N60.7119 (3)0.2094 (13)0.54313 (18)0.0348 (10)
H6NA0.764 (5)0.32 (2)0.549 (3)0.05 (2)*
H6NB0.731 (4)0.007 (19)0.555 (2)0.037 (16)*
N70.7580 (3)0.6324 (11)0.84251 (15)0.0335 (9)
N80.8271 (3)0.4576 (10)0.81702 (14)0.0297 (9)
N90.8504 (2)0.2236 (10)0.73690 (15)0.0274 (9)
N100.7183 (3)0.3347 (11)0.68245 (15)0.0281 (8)
N110.5809 (2)0.5994 (12)0.70605 (16)0.0300 (9)
H11N0.566 (4)0.587 (14)0.676 (2)0.025 (13)*
N120.5243 (3)0.7763 (12)0.74061 (17)0.0292 (9)
H12D0.469 (4)0.656 (15)0.743 (2)0.030 (14)*
H12E0.518 (4)1.019 (18)0.732 (2)0.037 (15)*
C10.5567 (3)0.3971 (14)0.47002 (17)0.0310 (10)
H10.61280.28040.46160.037*
C20.5337 (3)0.5087 (12)0.51798 (17)0.0242 (9)
C30.4448 (3)0.6664 (12)0.51286 (17)0.0247 (9)
C40.4345 (3)0.7879 (13)0.59211 (18)0.0280 (10)
H40.40160.88530.61870.034*
C50.5701 (3)0.5040 (12)0.56624 (17)0.0253 (9)
C60.3354 (4)0.7825 (17)0.4417 (2)0.0425 (13)
H6A0.35400.96590.41950.064*
H6B0.29250.87360.46630.064*
H6C0.30380.60130.42340.064*
C90.7999 (3)0.3896 (12)0.77082 (18)0.0242 (9)
C70.6873 (3)0.6765 (13)0.81121 (18)0.0309 (10)
H70.63050.79230.81870.037*
C80.7076 (3)0.5295 (12)0.76570 (18)0.0239 (9)
C100.8039 (3)0.2142 (13)0.69443 (18)0.0282 (10)
H100.83670.10510.66870.034*
C110.6678 (3)0.4953 (12)0.71848 (16)0.0242 (9)
C120.9129 (4)0.3412 (17)0.8420 (2)0.0430 (14)
H12A0.95540.23520.81840.065*
H12B0.89620.17390.86700.065*
H12C0.94420.53690.85710.065*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N10.0288 (19)0.046 (2)0.031 (2)−0.0051 (18)0.0019 (17)−0.0057 (19)
N20.0226 (18)0.042 (2)0.027 (2)−0.0047 (16)−0.0017 (15)0.0028 (18)
N30.0193 (16)0.030 (2)0.032 (2)0.0040 (15)−0.0007 (16)−0.0014 (16)
N40.0202 (18)0.034 (2)0.030 (2)−0.0008 (15)−0.0005 (14)−0.0005 (17)
N50.0208 (17)0.046 (3)0.029 (2)0.0086 (17)−0.0004 (16)0.0020 (19)
N60.0206 (19)0.036 (3)0.048 (3)0.0011 (18)0.0044 (18)−0.001 (2)
N70.0301 (19)0.039 (2)0.031 (2)0.0009 (18)−0.0001 (16)0.0056 (18)
N80.0227 (17)0.035 (2)0.031 (2)−0.0009 (15)−0.0055 (16)0.0078 (17)
N90.0163 (16)0.0300 (19)0.036 (2)−0.0027 (15)0.0012 (15)0.0041 (17)
N100.0222 (17)0.035 (2)0.0272 (19)0.0039 (15)−0.0023 (15)0.0049 (17)
N110.0158 (17)0.046 (2)0.028 (2)0.0042 (16)−0.0029 (15)−0.0013 (18)
N120.0126 (16)0.036 (2)0.039 (2)0.0009 (16)−0.0018 (15)−0.0010 (19)
C10.023 (2)0.043 (3)0.027 (2)−0.005 (2)0.0039 (19)0.002 (2)
C20.0166 (18)0.028 (2)0.029 (2)−0.0044 (17)0.0037 (16)0.0003 (18)
C30.020 (2)0.025 (2)0.029 (2)−0.0086 (16)−0.0021 (17)0.0052 (18)
C40.0210 (19)0.035 (3)0.029 (2)0.0055 (18)0.0048 (18)0.0001 (18)
C50.0191 (17)0.024 (2)0.033 (2)−0.0056 (15)0.0011 (16)0.0043 (17)
C60.032 (3)0.058 (4)0.037 (3)0.001 (2)−0.015 (2)−0.001 (3)
C90.0162 (17)0.023 (2)0.033 (2)−0.0034 (16)−0.0032 (17)0.0062 (18)
C70.0192 (19)0.039 (3)0.035 (2)−0.0018 (18)−0.0007 (19)0.006 (2)
C80.0158 (17)0.025 (2)0.031 (2)−0.0027 (15)0.0003 (17)0.0072 (18)
C100.022 (2)0.035 (2)0.028 (2)−0.0029 (18)0.0048 (18)0.0010 (19)
C110.0145 (17)0.031 (2)0.027 (2)−0.0012 (16)−0.0001 (16)0.0029 (18)
C120.029 (2)0.056 (3)0.044 (3)0.005 (2)−0.018 (2)0.010 (3)

Geometric parameters (Å, °)

N1—C11.314 (7)N11—C111.332 (5)
N1—N21.369 (6)N11—N121.412 (6)
N2—C31.333 (6)N11—H11N0.85 (6)
N2—C61.470 (6)N12—H12D0.91 (6)
N3—C41.312 (6)N12—H12E0.97 (7)
N3—C31.364 (6)C1—C21.415 (7)
N4—C51.345 (6)C1—H10.9400
N4—C41.350 (6)C2—C31.401 (6)
N5—C51.348 (6)C2—C51.413 (6)
N5—N61.415 (6)C4—H40.9400
N5—H5N0.84 (7)C6—H6A0.9700
N6—H6NA0.86 (7)C6—H6B0.9700
N6—H6NB0.89 (7)C6—H6C0.9700
N7—C71.322 (6)C9—C81.415 (5)
N7—N81.375 (6)C7—C81.395 (7)
N8—C91.343 (6)C7—H70.9400
N8—C121.458 (6)C8—C111.411 (6)
N9—C101.331 (6)C10—H100.9400
N9—C91.332 (6)C12—H12A0.9700
N10—C101.334 (6)C12—H12B0.9700
N10—C111.364 (6)C12—H12C0.9700
C1—N1—N2106.1 (4)N3—C4—N4128.7 (4)
C3—N2—N1111.5 (4)N3—C4—H4115.7
C3—N2—C6127.8 (4)N4—C4—H4115.7
N1—N2—C6120.5 (4)N4—C5—N5115.7 (4)
C4—N3—C3111.9 (4)N4—C5—C2119.6 (4)
C5—N4—C4118.4 (4)N5—C5—C2124.7 (4)
C5—N5—N6119.4 (4)N2—C6—H6A109.5
C5—N5—H5N120 (4)N2—C6—H6B109.5
N6—N5—H5N119 (4)H6A—C6—H6B109.5
N5—N6—H6NA97 (5)N2—C6—H6C109.5
N5—N6—H6NB108 (4)H6A—C6—H6C109.5
H6NA—N6—H6NB97 (6)H6B—C6—H6C109.5
C7—N7—N8105.7 (4)N9—C9—N8126.4 (4)
C9—N8—N7111.6 (4)N9—C9—C8127.3 (4)
C9—N8—C12127.8 (4)N8—C9—C8106.2 (4)
N7—N8—C12120.2 (4)N7—C7—C8111.6 (4)
C10—N9—C9110.8 (4)N7—C7—H7124.2
C10—N10—C11117.1 (4)C8—C7—H7124.2
C11—N11—N12119.7 (4)C7—C8—C11140.2 (4)
C11—N11—H11N118 (3)C7—C8—C9104.9 (4)
N12—N11—H11N122 (4)C11—C8—C9114.8 (4)
N11—N12—H12D107 (4)N9—C10—N10130.4 (5)
N11—N12—H12E111 (4)N9—C10—H10114.8
H12D—N12—H12E116 (5)N10—C10—H10114.8
N1—C1—C2111.0 (4)N11—C11—N10115.7 (4)
N1—C1—H1124.5N11—C11—C8124.7 (4)
C2—C1—H1124.5N10—C11—C8119.5 (4)
C3—C2—C5115.0 (4)N8—C12—H12A109.5
C3—C2—C1104.2 (4)N8—C12—H12B109.5
C5—C2—C1140.7 (4)H12A—C12—H12B109.5
N2—C3—N3126.4 (4)N8—C12—H12C109.5
N2—C3—C2107.2 (4)H12A—C12—H12C109.5
N3—C3—C2126.4 (4)H12B—C12—H12C109.5
C1—N1—N2—C31.0 (5)C3—C2—C5—N5−178.1 (4)
C1—N1—N2—C6177.0 (4)C1—C2—C5—N53.4 (9)
C7—N7—N8—C9−0.8 (5)C10—N9—C9—N8−177.2 (4)
C7—N7—N8—C12−175.0 (4)C10—N9—C9—C82.7 (6)
N2—N1—C1—C2−0.6 (6)N7—N8—C9—N9−179.8 (4)
N1—C1—C2—C30.1 (6)C12—N8—C9—N9−6.0 (7)
N1—C1—C2—C5178.6 (5)N7—N8—C9—C80.3 (5)
N1—N2—C3—N3−179.7 (4)C12—N8—C9—C8174.0 (5)
C6—N2—C3—N34.7 (8)N8—N7—C7—C81.0 (6)
N1—N2—C3—C2−0.9 (5)N7—C7—C8—C11−177.1 (5)
C6—N2—C3—C2−176.6 (5)N7—C7—C8—C9−0.8 (6)
C4—N3—C3—N2178.0 (4)N9—C9—C8—C7−179.7 (4)
C4—N3—C3—C2−0.5 (6)N8—C9—C8—C70.3 (5)
C5—C2—C3—N2−178.5 (4)N9—C9—C8—C11−2.3 (7)
C1—C2—C3—N20.5 (5)N8—C9—C8—C11177.7 (4)
C5—C2—C3—N30.3 (6)C9—N9—C10—N10−1.5 (7)
C1—C2—C3—N3179.3 (4)C11—N10—C10—N90.0 (7)
C3—N3—C4—N4−0.3 (7)N12—N11—C11—N10−178.3 (4)
C5—N4—C4—N31.3 (8)N12—N11—C11—C84.0 (7)
C4—N4—C5—N5177.5 (4)C10—N10—C11—N11−177.1 (4)
C4—N4—C5—C2−1.5 (6)C10—N10—C11—C80.6 (6)
N6—N5—C5—N4176.9 (4)C7—C8—C11—N11−6.0 (9)
N6—N5—C5—C2−4.1 (7)C9—C8—C11—N11177.9 (4)
C3—C2—C5—N40.8 (6)C7—C8—C11—N10176.4 (5)
C1—C2—C5—N4−177.7 (6)C9—C8—C11—N100.4 (6)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C12—H12B···N1i0.972.653.297 (7)124
C6—H6C···N7ii0.972.543.410 (7)150
N11—H11N···N40.85 (6)2.11 (6)2.948 (6)170 (5)
N5—H5N···N100.84 (7)2.13 (7)2.961 (6)170 (5)
N12—H12E···N9iii0.97 (7)2.56 (6)3.125 (5)117 (4)
N12—H12D···N9iv0.91 (6)2.24 (6)3.125 (6)166 (5)
N6—H6NB···N3v0.89 (7)2.59 (6)3.251 (6)131 (5)
N6—H6NA···N3vi0.86 (7)2.30 (7)3.149 (6)168 (7)

Symmetry codes: (i) −x+3/2, y−1/2, z+1/2; (ii) −x+1, −y+1, z−1/2; (iii) x−1/2, −y+3/2, z; (iv) x−1/2, −y+1/2, z; (v) x+1/2, −y+1/2, z; (vi) x+1/2, −y+3/2, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: JH2082).

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