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In the title compound, C14H19N3, the bond distances within the heterocyclic portion of the mol­ecule indicate incomplete [pi] delocalization. The mol­ecules are linked into stacks by a combination of two C-H...[pi](pyrazole) hydrogen bonds and two independent [pi]-[pi] stacking inter­actions between inversion-related pyrimidine rings. The significance of this study lies in its observation of significant differences in both mol­ecular conformation and supra­molecular aggregation between the title compound, an example of a 2-alkyl­pyrazolo[1,5-a]pyrimidine, and some analogous 2-aryl­pyrazolo[1,5-a]pyrimidines.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S010827010802266X/sk3259sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S010827010802266X/sk3259Isup2.hkl
Contains datablock I

CCDC reference: 703719

Comment top

Pyrazolo[1,5-b]pyrimidines are purine analogues, and their pharmacological activity (Novinson et al., 1976; Senga et al., 1981) has prompted interest in the development of efficient, general procedures for their synthesis. One attractive route (Portilla et al., 2005) to such compounds involves the condensation of a substituted 5-amino-1H-pyrazole, (A) (see scheme), with a 2-acylcyclopentanone, (B), to give the 2,5-disubstituted product (C). We report here the molecular and supramolecular structure of the title compound, (I) (Fig. 1), which was prepared using a simple fusion-induced condensation reaction between 5-amino-3-tert-butyl-1H-pyrazole and 2-acetylcyclopentanone under solvent-free conditions. We compare the structure of (I) with those of the aryl-substituted analogues (II)–(V), which were all prepared using similar condensation reactions under solvent-free conditions but induced by microwave irradiation (Portilla et al., 2005).

By contrast with the conformations found for compounds (II)–(V), where the carbocyclic rings all adopt envelope conformations, the corresponding ring in (I) is effectively planar; the maximum deviations from the mean plane of the ring atoms in (I) is only 0.024 (3) Å, for atom C7. There is no obvious interpretation of this difference. While the tricyclic skeleton in (I) is effectively planar, the tert-butyl group is rotated by ca 10° from the conformation, which corresponds to an approximate mirror symmetry, as shown by the key torsion angles (Table 1). However, the pattern of the bond distances within the heterocyclic system in (I) (Table 1) shows a close similarity with those in (II)–(V) and, as before, this suggests a naphthalene-type arrangement of the ten π electrons in this system rather than full delocalization.

Despite the presence of two ring N atoms, N1 and N4, each carrying an in-plane lone pair of electrons potentially available for hydrogen-bond formation, there are, in fact, no C—H···N hydrogen bonds in the structure of (I). In this respect, (I) resembles compounds (II)–(IV), although a single C—H···N interaction is present in (V). The molecules of (I) are linked by a combination of C—H···π(pyrazone) hydrogen bonds (Table 2) and ππ stacking interactions. Atom C6 in the molecule at (x, y, z) acts as hydrogen-bond donor, via atoms H6A and H6B, respectively, to the pyrazole rings in the molecules at (-x + 1, -y + 1, -z + 1) and (-x + 2, -y + 1, -z + 1), respectively. Thus the pyrazole ring accepts a C—H bond onto each face, such that the angle H6A···Cg1i···H6Biii [Cg1 represents the centroid of the pyrazole ring; symmetry codes: (i) -x + 1, -y + 1, -z + 1; (ii) x - 1, y, z] is 150°. In addition, the pyrimidine rings of the molecules at (x, y, z) and (-x + 1, -y + 1, z), which are strictly parallel because they are related by inversion, have an interplanar spacing of 3.422 (2) Å and a ring-centroid separation of 3.611 (2) Å, corresponding to a ring centroid offset of 1.152 (2) Å. Similarly, for the pyrimidine rings of the molecules at (x, y, z) and (-x + 2, -y + 1, -z + 1), the interplanar separation is 3.443 (2) Å and the ring-centroid separation is 3.674 (2) Å, corresponding in this case to a ring-centroid offset of 1.282 (2) Å. The combined and cooperative effect of the C—H···π hydrogen bonds and the ππ stacking interaction is to link the molecules into a stack running parallel to the [100] direction, in which alternate molecules are related by inversion (Fig. 2).

In the isostructural compounds (II)–(IV) (Portilla et al., 2005), the molecules are linked into chains by a single C—H···π(pyrazole) hydrogen bond, again involving atom C6 as the donor. In these hydrogen bonds, the H···A and D···A distances are all significantly greater than the corresponding distances in (I), while the organization of the molecules within the chains in (II)–(IV) effectively precludes the formation of a second C—H···π hydrogen bond, as found in (I). There is a single C—H···N hydrogen bond in (V), with one of the C—H bonds in the pendent aryl group providing the donor and the pyrimidine ring atom N4 as the acceptor. The resulting C(7) (Bernstein et al., 1995) chains are then linked into a sheet by means of a ππ stacking interaction between inversion-related heterocyclic rings. Compound (V) is thus the only member of this series so far observed to exhibit a C—H···N hydrogen bond, while (I) is the sole member in which the pyrazole ring acts as a double acceptor of hydrogen bonds.

Only in (V) does the substituent at taom C2 play any direct role in the hydrogen bonding. Nonetheless the pattern of supramolecular aggregation in (I) is different from that in the isomorphous series (II)–(IV); likewise the conformational difference between (I) and (II)–(V) involves the carbocyclic ring remote from the substituent at C2. Very subtle factors appear to connect the nature of the substituent at C2 with both the overall molecular conformation and the direction-specific intermolecular forces, making structure predictions extremely uncertain.

Related literature top

For related literature, see: Bernstein et al. (1995); Novinson et al. (1976); Portilla et al. (2005); Senga et al. (1981); Spek (2003).

Experimental top

Equimolar quantities (2 mmol of each component) of 5-amino-3-tert-butyl-1H-pyrazole and 2-acetylcyclopentanone were thoroughly mixed at room temperature. The mixture was heated in an oil-bath at 393 K for 1.5 min. It was then stirred and allowed to cool to room temperature when it solidified. The solid material was extracted with ethanol; after removal of this solvent, the product (I) was recrystallized from dimethylformamide to give yellow crystals suitable for single-crystal X-ray diffraction (yield 93%, m.p. 459–461 K). MS (70 eV) m/z (%) 229 (64, M+), 214 (100), 187 (87), 106 (19), 53 (20), 41 (527), 39 (40).

Refinement top

Crystals of (I) are triclinic; the space group P1 was selected, and confirmed by the structure analysis. All H atoms were located in difference maps and then treated as riding atoms in geometrically idealized positions, with C—H distances of 0.95 Å (pyrazole), 0.98 Å (CH3) or 0.99 Å (CH2), and with Uiso(H) = kUeq(C), where k = 1.5 for the methyl groups and 1.2 for all other H atoms. The ADDSYM routine in PLATON (Spek, 2003) suggested a possible revision of the space group to C2/m with Z' = 1/2, but in the revised unit-cell the angles α and γ deviated from 90° by more than 0.3° in each case; moreover, the orientation of the tert-butyl group relative to the adjacent ring, as indicated by the leading torsion angles (Table 1), suffices to rule out the possibility of any internal mirror symmetry for the molecule of (I).

Computing details top

Data collection: COLLECT (Hooft, 1999); cell refinement: DIRAX/LSQ (Duisenberg et al., 2000); data reduction: EVALCCD (Duisenberg et al., 2003); program(s) used to solve structure: SIR2004 (Burla et al., 2005); program(s) used to refine structure: OSCAIL (McArdle, 2003) and SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PRPKAPPA (Ferguson, 1999).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.
[Figure 2] Fig. 2. A stereoview of part of the crystal structure of (I), showing the formation of a stack of molecules along [100] built from a combination of C—H···π(pyrazole) hydrogen bonds and ππ stacking interactions. For the sake of clarity, H atoms not involved in the motifs shown have been omitted.
2-tert-Butyl-5-methyl-7,8-dihydro-6H- cyclopenta[e]pyrazolo[1,5-a]pyrimidine top
Crystal data top
C14H19N3Z = 2
Mr = 229.32F(000) = 248
Triclinic, P1Dx = 1.205 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 6.8665 (6) ÅCell parameters from 2898 reflections
b = 9.4084 (14) Åθ = 3.3–27.5°
c = 11.147 (2) ŵ = 0.07 mm1
α = 91.611 (14)°T = 120 K
β = 107.728 (14)°Block, yellow
γ = 111.097 (12)°0.38 × 0.37 × 0.25 mm
V = 632.22 (18) Å3
Data collection top
Bruker–Nonius KappaCCD
diffractometer
2898 independent reflections
Radiation source: Bruker–Nonius FR591 rotating anode1804 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.049
Detector resolution: 9.091 pixels mm-1θmax = 27.5°, θmin = 3.3°
ϕ and ω scansh = 88
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
k = 1212
Tmin = 0.966, Tmax = 0.982l = 1414
15695 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.062Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.180H-atom parameters constrained
S = 1.11 w = 1/[σ2(Fo2) + (0.0576P)2 + 0.6693P]
where P = (Fo2 + 2Fc2)/3
2898 reflections(Δ/σ)max = 0.001
158 parametersΔρmax = 0.29 e Å3
0 restraintsΔρmin = 0.29 e Å3
Crystal data top
C14H19N3γ = 111.097 (12)°
Mr = 229.32V = 632.22 (18) Å3
Triclinic, P1Z = 2
a = 6.8665 (6) ÅMo Kα radiation
b = 9.4084 (14) ŵ = 0.07 mm1
c = 11.147 (2) ÅT = 120 K
α = 91.611 (14)°0.38 × 0.37 × 0.25 mm
β = 107.728 (14)°
Data collection top
Bruker–Nonius KappaCCD
diffractometer
2898 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
1804 reflections with I > 2σ(I)
Tmin = 0.966, Tmax = 0.982Rint = 0.049
15695 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0620 restraints
wR(F2) = 0.180H-atom parameters constrained
S = 1.11Δρmax = 0.29 e Å3
2898 reflectionsΔρmin = 0.29 e Å3
158 parameters
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
N10.8353 (3)0.4136 (2)0.75796 (18)0.0259 (5)
N40.6022 (3)0.2937 (2)0.42163 (18)0.0269 (5)
N90.7835 (3)0.4343 (2)0.63402 (17)0.0226 (4)
C20.7503 (4)0.2585 (3)0.7516 (2)0.0247 (5)
C30.6462 (4)0.1820 (3)0.6260 (2)0.0256 (5)
C3A0.6684 (4)0.2966 (3)0.5496 (2)0.0242 (5)
C50.6507 (4)0.4280 (3)0.3787 (2)0.0270 (5)
C5A0.7658 (4)0.5696 (3)0.4619 (2)0.0244 (5)
C60.8372 (4)0.7323 (3)0.4333 (2)0.0296 (6)
C70.9487 (5)0.8335 (3)0.5664 (3)0.0358 (6)
C80.9526 (4)0.7262 (3)0.6686 (2)0.0301 (6)
C8A0.8318 (4)0.5711 (3)0.5901 (2)0.0237 (5)
C210.7785 (4)0.1915 (3)0.8733 (2)0.0295 (6)
C220.6399 (6)0.0200 (3)0.8464 (3)0.0541 (9)
C231.0238 (5)0.2195 (4)0.9372 (3)0.0586 (10)
C240.7074 (6)0.2702 (4)0.9638 (3)0.0500 (8)
C510.5778 (4)0.4261 (3)0.2373 (2)0.0331 (6)
H30.57480.07380.59860.031*
H6A0.70790.75350.38190.035*
H6B0.94340.75100.38650.035*
H7A1.10180.90400.57630.043*
H7B0.86430.89650.57610.043*
H8A1.10630.74140.71970.036*
H8B0.87550.74300.72620.036*
H22A0.48340.00220.80490.081*
H22B0.65840.02200.92670.081*
H22C0.68810.03140.79020.081*
H23A1.07000.16540.88170.088*
H23B1.04430.18071.01890.088*
H23C1.11370.33030.95180.088*
H24A0.79940.38080.98310.075*
H24B0.72570.22561.04300.075*
H24C0.55140.25460.92360.075*
H51A0.50580.31920.19380.050*
H51B0.70720.48080.21240.050*
H51C0.47290.47720.21340.050*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0311 (11)0.0238 (10)0.0211 (10)0.0088 (8)0.0084 (8)0.0069 (8)
N40.0298 (10)0.0304 (11)0.0225 (10)0.0123 (9)0.0106 (8)0.0072 (8)
N90.0262 (10)0.0206 (10)0.0219 (10)0.0087 (8)0.0096 (8)0.0057 (8)
C20.0259 (12)0.0240 (12)0.0258 (12)0.0094 (10)0.0114 (10)0.0055 (9)
C30.0253 (12)0.0234 (12)0.0281 (13)0.0083 (10)0.0101 (10)0.0046 (10)
C3A0.0230 (11)0.0258 (12)0.0243 (12)0.0093 (10)0.0089 (9)0.0024 (9)
C50.0270 (12)0.0303 (13)0.0273 (13)0.0127 (10)0.0118 (10)0.0073 (10)
C5A0.0216 (11)0.0284 (12)0.0282 (13)0.0117 (10)0.0122 (10)0.0089 (10)
C60.0313 (13)0.0307 (13)0.0331 (14)0.0143 (11)0.0159 (11)0.0145 (11)
C70.0411 (15)0.0264 (13)0.0370 (15)0.0102 (11)0.0125 (12)0.0099 (11)
C80.0337 (13)0.0229 (12)0.0308 (13)0.0081 (10)0.0105 (11)0.0047 (10)
C8A0.0226 (11)0.0217 (12)0.0310 (13)0.0099 (9)0.0127 (10)0.0079 (9)
C210.0359 (14)0.0252 (12)0.0234 (12)0.0087 (10)0.0080 (10)0.0066 (10)
C220.083 (2)0.0268 (15)0.0356 (16)0.0061 (15)0.0152 (16)0.0091 (12)
C230.0454 (18)0.079 (2)0.053 (2)0.0264 (17)0.0129 (15)0.0390 (18)
C240.075 (2)0.0549 (19)0.0335 (16)0.0312 (17)0.0285 (15)0.0193 (14)
C510.0389 (14)0.0375 (14)0.0255 (13)0.0166 (12)0.0120 (11)0.0090 (11)
Geometric parameters (Å, º) top
N1—C21.353 (3)C51—H51A0.9800
C2—C31.397 (3)C51—H51B0.9800
C3—C3A1.387 (3)C51—H51C0.9800
C3A—N41.355 (3)C21—C221.514 (4)
N4—C51.329 (3)C21—C241.524 (4)
C5—C5A1.409 (3)C21—C231.534 (4)
C8A—N91.354 (3)C6—H6A0.9900
N9—N11.356 (3)C6—H6B0.9900
C3A—N91.389 (3)C7—H7A0.9900
C5A—C8A1.360 (3)C7—H7B0.9900
C5A—C61.506 (3)C24—H24A0.9800
C6—C71.549 (4)C24—H24B0.9800
C7—C81.544 (3)C24—H24C0.9800
C8—C8A1.482 (3)C22—H22A0.9800
C2—C211.501 (3)C22—H22B0.9800
C8—H8A0.9900C22—H22C0.9800
C8—H8B0.9900C23—H23A0.9800
C3—H30.9500C23—H23B0.9800
C5—C511.498 (3)C23—H23C0.9800
C8A—N9—N1126.38 (19)C2—C21—C24109.9 (2)
C8A—N9—C3A120.51 (19)C22—C21—C24109.3 (2)
N1—N9—C3A113.11 (18)C2—C21—C23109.1 (2)
N4—C3A—C3133.2 (2)C22—C21—C23109.6 (3)
N4—C3A—N9121.8 (2)C24—C21—C23108.6 (3)
C3—C3A—N9105.07 (19)C5A—C6—C7104.08 (19)
C2—N1—N9103.65 (18)C5A—C6—H6A110.9
C5—N4—C3A117.7 (2)C7—C6—H6A110.9
N1—C2—C3112.3 (2)C5A—C6—H6B110.9
N1—C2—C21118.8 (2)C7—C6—H6B110.9
C3—C2—C21128.9 (2)H6A—C6—H6B109.0
N9—C8A—C5A118.2 (2)C8—C7—C6108.3 (2)
N9—C8A—C8126.4 (2)C8—C7—H7A110.0
C5A—C8A—C8115.3 (2)C6—C7—H7A110.0
C8A—C8—C7102.2 (2)C8—C7—H7B110.0
C8A—C8—H8A111.3C6—C7—H7B110.0
C7—C8—H8A111.3H7A—C7—H7B108.4
C8A—C8—H8B111.3C21—C24—H24A109.5
C7—C8—H8B111.3C21—C24—H24B109.5
H8A—C8—H8B109.2H24A—C24—H24B109.5
C3A—C3—C2105.9 (2)C21—C24—H24C109.5
C3A—C3—H3127.1H24A—C24—H24C109.5
C2—C3—H3127.1H24B—C24—H24C109.5
N4—C5—C5A121.9 (2)C21—C22—H22A109.5
N4—C5—C51118.1 (2)C21—C22—H22B109.5
C5A—C5—C51120.0 (2)H22A—C22—H22B109.5
C8A—C5A—C5119.9 (2)C21—C22—H22C109.5
C8A—C5A—C6109.9 (2)H22A—C22—H22C109.5
C5—C5A—C6130.2 (2)H22B—C22—H22C109.5
C5—C51—H51A109.5C21—C23—H23A109.5
C5—C51—H51B109.5C21—C23—H23B109.5
H51A—C51—H51B109.5H23A—C23—H23B109.5
C5—C51—H51C109.5C21—C23—H23C109.5
H51A—C51—H51C109.5H23A—C23—H23C109.5
H51B—C51—H51C109.5H23B—C23—H23C109.5
C2—C21—C22110.4 (2)
C8A—N9—C3A—N40.5 (3)C3A—N4—C5—C5A0.3 (3)
N1—N9—C3A—N4179.99 (19)C3A—N4—C5—C51179.9 (2)
C8A—N9—C3A—C3179.3 (2)N9—C8A—C5A—C50.1 (3)
N1—N9—C3A—C30.2 (2)C8—C8A—C5A—C5179.7 (2)
C8A—N9—N1—C2179.4 (2)N9—C8A—C5A—C6179.47 (19)
C3A—N9—N1—C20.0 (2)C8—C8A—C5A—C60.3 (3)
C3—C3A—N4—C5179.6 (2)N4—C5—C5A—C8A0.4 (3)
N9—C3A—N4—C50.2 (3)C51—C5—C5A—C8A180.0 (2)
N9—N1—C2—C30.1 (2)N4—C5—C5A—C6179.6 (2)
N9—N1—C2—C21179.4 (2)C51—C5—C5A—C60.8 (4)
N1—N9—C8A—C5A179.8 (2)N1—C2—C21—C22170.4 (2)
C3A—N9—C8A—C5A0.3 (3)N1—C2—C21—C2369.1 (3)
N1—N9—C8A—C80.5 (4)N1—C2—C21—C2449.8 (3)
C3A—N9—C8A—C8179.9 (2)C3—C2—C21—C2210.1 (4)
N9—C8A—C8—C7178.2 (2)C3—C2—C21—C23110.4 (3)
C5A—C8A—C8—C72.0 (3)C3—C2—C21—C24130.7 (3)
N4—C3A—C3—C2180.0 (2)C8A—C5A—C6—C72.5 (3)
N9—C3A—C3—C20.2 (2)C5—C5A—C6—C7178.2 (2)
N1—C2—C3—C3A0.2 (3)C8A—C8—C7—C63.5 (3)
C21—C2—C3—C3A179.3 (2)C5A—C6—C7—C83.7 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C6—H6A···Cg1i0.992.763.602 (3)144
C6—H6B···Cg1ii0.992.703.581 (3)148
Symmetry codes: (i) x+1, y+1, z+1; (ii) x+2, y+1, z+1.

Experimental details

Crystal data
Chemical formulaC14H19N3
Mr229.32
Crystal system, space groupTriclinic, P1
Temperature (K)120
a, b, c (Å)6.8665 (6), 9.4084 (14), 11.147 (2)
α, β, γ (°)91.611 (14), 107.728 (14), 111.097 (12)
V3)632.22 (18)
Z2
Radiation typeMo Kα
µ (mm1)0.07
Crystal size (mm)0.38 × 0.37 × 0.25
Data collection
DiffractometerBruker–Nonius KappaCCD
diffractometer
Absorption correctionMulti-scan
(SADABS; Sheldrick, 2003)
Tmin, Tmax0.966, 0.982
No. of measured, independent and
observed [I > 2σ(I)] reflections
15695, 2898, 1804
Rint0.049
(sin θ/λ)max1)0.650
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.062, 0.180, 1.11
No. of reflections2898
No. of parameters158
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.29, 0.29

Computer programs: COLLECT (Hooft, 1999), DIRAX/LSQ (Duisenberg et al., 2000), EVALCCD (Duisenberg et al., 2003), SIR2004 (Burla et al., 2005), OSCAIL (McArdle, 2003) and SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2003), SHELXL97 (Sheldrick, 2008) and PRPKAPPA (Ferguson, 1999).

Selected geometric parameters (Å, º) top
N1—C21.353 (3)C5—C5A1.409 (3)
C2—C31.397 (3)C8A—N91.354 (3)
C3—C3A1.387 (3)N9—N11.356 (3)
C3A—N41.355 (3)C3A—N91.389 (3)
N4—C51.329 (3)C5A—C8A1.360 (3)
N1—C2—C21—C22170.4 (2)C3—C2—C21—C2210.1 (4)
N1—C2—C21—C2369.1 (3)C3—C2—C21—C23110.4 (3)
N1—C2—C21—C2449.8 (3)C3—C2—C21—C24130.7 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C6—H6A···Cg1i0.992.763.602 (3)144
C6—H6B···Cg1ii0.992.703.581 (3)148
Symmetry codes: (i) x+1, y+1, z+1; (ii) x+2, y+1, z+1.
 

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