A unique tautomer of 1-n-hexyl-3-phenyl-1H-pyrazol-5-ol

In the title compound, C₁₅H₂₀N₂O, the bond distances and angles are consistent with the presence of the hydroxy tautomer. This tautomer was unambiguously determined by the clear presence of a H atom bonded to oxygen, as well as the total absence of any residual electron density around the N atom in the heterocycle, thus precluding any possibility of desmotropism.

S1. Comment

Pyrazolones are an important family of organic heterocyclic compounds (Elguero, 1996), which have attracted much attention due to their applications as drugs (Gürzov et al., 2000), extractants (Marchetti et al., 2005; Pettinari et al., 2000) or dyes (Emeleus et al., 2001), and because of the prototropic tautomerism they exhibit (Elguero et al., 1976). As a consequence, they have been extensively studied, both in solution and in the crystalline phase (Chmutova et al., 2001). Unsubstituted pyrazolones and 1-arylpyrazolones (and their derivatives) are commonly described in the literature, while their 1-alkyl homologues are seldom mentioned. This situation is quite unfortunate, since 1-alkylpyrazolones are more soluble than their 1-aryl counterparts, which would make them valuable products. It is worthy of note that 3-phenylpyrazolones are very scarce in the literature, with only very few reported examples (Belmar et al., 1999; Marchetti et al., 2005). Therefore, 1-n-alkyl-3-phenyl-5-pyrazolones are even rarer compounds.

Some years ago, a project aimed at the synthesis of 1-alkyl-3-methyl-5-pyrazolones and their derivatives was started (Bartulin et al., 1992). A few years later, 1-n-butyl- and 1-n-hexyl-3-phenyl-5-pyrazolones were synthesized (Belmar et al., 1999). The new objective was to observe the effect, if any, on the tautomeric equilibrium of changing from a methyl group to a phenyl group at position 3. However, the structures of these new compounds could not be fully established in dimethylsulfoxide solution, and it was not possible to decide between the NH and OH tautomers, or indeed whether the two forms were both present as an equilibrium mixture. In chloroform solution, however, the presence of the CH form was clearly established (see scheme). These results are consistent with previous observations on 1-n-alkyl-3-methyl-5-pyrazolones, whose solid-state structures could not be firmly established using IR spectroscopy.

It has already been reported (Foces-Foces et al., 1997) that, in the crystalline state, 1-phenyl-3-methyl-5-pyrazolone exhibits desmotropy, i.e. the NH and OH tautomers co-exist in the unit cell. On the other hand, the 1-(4-bromophenyl) analogue occurs only in the NH form in the solid state. Thus, it is interesting to establish the solid-state structures of similar related compounds.

As a new contribution to the knowledge of tautomerism in pyrazolone derivatives, we report here the first crystal structure of a 1-alkyl-3-phenyl-5-hydroxypyrazole, namely that of 1-n-hexyl-5-hydroxy-3-phenyl-1H-pyrazole, (I) (Fig. 1).

The clear presence of the hydroxyl H atom in the difference Fourier synthesis, and the absence of any residual electronic density in the vicinity of N2, confirm that compound (I) crystallizes as a pure hydroxyl tautomer and that no desmotropism is present (Foces-Foces et al., 1997). Moreover, the bond distances around the heterocycle (Table 1) are fully consistent with this conclusion: N2—C7 and C8—C9 correspond to well defined double bonds, while C7—C8, even though it is shorter than in any of the closely related compounds (Belmar et al., 2004; Bothe et al., 2001), exhibits significant single-bond character. Finally, C9—O1 is clearly a single bond, as expected from the presence of H1 bonded to O1. Fig. 2 shows the V-shaped nature of the molecule, with the alkylic atom C10 at the vertex of the V. The aromatic part is almost planar, with a maximum deviation of 0.08 (1) Å (for atom N1) from the mean plane containing both groups. Also effectively planar is the fully extended alkyl chain, where the maximum deviation from planarity is 0.09 (1) Å for atom C10. The dihedral angle between the aryl and alkyl planes is 65.9 (1)°.

The simultaneous presence in the heterocycle of a hydroxyl group, a quite efficient hydrogen-bond donor and a non-protonated N atom, a good acceptor for this type of interaction, results in the formation of a very strong O—H···N bond linking the molecules related by the c-glide into tightly connected chains running along [001]. The interaction is strong enough to `freeze' the H atom, permitting its easy location in difference maps and also allowing its free refinement without any restraints. The V-shaped molecules lie on both sides of the glide plane, with their vertices almost aligned on the plane and in a (displaced) mirror-like fashion. Thus, when observed in projection down [001], an `X-like' view of the array is obtained (Fig. 2). This particular shape of the chains allows them to interdigitate neatly along [100], with alkyl groups in one chain fitting the voids left by adjacent aromatic groups in neighbouring chains. This interdigitation in consecutive chains along [100] defines a pseudo two-dimensional structure parallel to (010), centred on y = 0 and 1/2 (Fig. 2). The planes are well separated along [010], and lateral contacts between these structures are purely of the van der Waals type.

S2. Experimental

1-n-Hexyl-3-phenyl-5-hydroxypyrazol was obtained in a two-step process, as reported elsewhere (Belmar et al., 1999). The product was crystallized from an ethanolic solution saturated with water at boiling temperature [yields 80% (first step, 3-phenyl-5-pyrazolone) and 40% (second step), m.p. 434–437 K]. Single crystals were selected from the crystallized material.

S3. Refinement

Those H atoms defined by the stereochemistry were placed in their theoretical positions (Csp²—H = 0.97 Å and Csp³—H = 0.96%A) and allowed to ride. The methyl group was allowed to rotate around its local threefold axis. Atom H1 attached to O1 was found in a difference Fourier map and refined freely. Isotropic displacement parameters for all H atoms except H1 were defined as U_iso(H) = xU_eq(parent), with x = 1.2 or 1.5 for non-methyl or methyl H atoms, respectively. As no significant anomalous scattering effects were present, Friedel opposites were merged before refinement. This resulted in a less than ideal data-to-parameter ratio (approximately 7).

Computing details

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP in SHELXTL/PC (Sheldrick, 1994); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2003).

Figures

Fig. 1. A plot of the structure of (I), viewed down b, showing the way in which the chains (running along c) are formed. Displacement ellipsoids are drawn at the 40% probability level. Only the reference molecule in the asymmetric unit has been drawn with full ellipsoids, symmetry-related ones being represented with open ellipsoids. The strong O—H···N bond is shown by a double dashed line. [Symmetry code: (i) ? Please complete. Code for atom on right-hand side?]

Fig. 2. A packing diagram, viewed down c, showing the stacking of the X-shaped chains. One single chain is shown with heavy lines, for clarity. Note the way in which vertically displaced chains interdigitate to form broad well separated two-dimensional structures.

1-n-hexyl-5-hydroxy-3-phenyl-1H-pyrazole

Crystal data

C15H20N2O	F(000) = 528
Mr = 244.33	Dx = 1.199 Mg m^−3
Monoclinic, Cc	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C -2yc	Cell parameters from 558 reflections
a = 10.0979 (4) Å	θ = 3.8–23.0°
b = 13.4026 (7) Å	µ = 0.08 mm^−1
c = 10.6047 (4) Å	T = 170 K
β = 109.479 (3)°	Block, colourless
V = 1353.07 (10) Å^3	0.28 × 0.22 × 0.17 mm
Z = 4

Data collection

Bruker SMART CCD area-detector diffractometer	906 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.030
Graphite monochromator	θmax = 25.0°, θmin = 4.1°
ϕ and ω scans	h = −12→10
3616 measured reflections	k = −15→14
1167 independent reflections	l = −10→12

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)] = 0.047	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.109	w = 1/[σ^2(Fo^2) + (0.0373P)^2 + 1.0265P] where P = (Fo^2 + 2Fc^2)/3
S = 1.13	(Δ/σ)max = 0.002
1167 reflections	Δρmax = 0.17 e Å^−3
169 parameters	Δρmin = −0.17 e Å^−3
2 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: 0.016 (2)

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

	x	y	z	Uiso*/Ueq
O1	0.4587 (3)	0.4129 (2)	0.2820 (3)	0.0498 (9)
H1A	0.486 (5)	0.427 (4)	0.215 (5)	0.058 (16)*
N1	0.4714 (4)	0.4815 (2)	0.4858 (3)	0.0432 (10)
N2	0.5559 (4)	0.5436 (2)	0.5844 (3)	0.0459 (10)
C1	0.7830 (6)	0.6761 (3)	0.7423 (4)	0.0582 (14)
H1	0.7082	0.6679	0.7741	0.070*
C2	0.8997 (8)	0.7319 (3)	0.8153 (5)	0.0734 (19)
H2	0.9019	0.7616	0.8952	0.088*
C3	1.0120 (7)	0.7435 (4)	0.7704 (7)	0.095 (2)
H3	1.0913	0.7789	0.8207	0.114*
C4	1.0046 (6)	0.7026 (5)	0.6518 (8)	0.116 (3)
H4	1.0788	0.7117	0.6195	0.139*
C5	0.8905 (6)	0.6482 (5)	0.5782 (7)	0.084 (2)
H5	0.8887	0.6210	0.4969	0.101*
C6	0.7787 (5)	0.6327 (3)	0.6218 (4)	0.0459 (12)
C7	0.6611 (5)	0.5702 (3)	0.5416 (3)	0.0382 (10)
C8	0.6461 (4)	0.5255 (3)	0.4176 (3)	0.0364 (10)
H8	0.7059	0.5319	0.3677	0.044*
C9	0.5259 (5)	0.4710 (3)	0.3859 (4)	0.0404 (11)
C10	0.3486 (7)	0.4334 (4)	0.4996 (5)	0.0674 (18)
H10A	0.3713	0.4092	0.5905	0.081*
H10B	0.3248	0.3761	0.4404	0.081*
C11	0.2210 (6)	0.5017 (4)	0.4677 (5)	0.0698 (17)
H11A	0.1463	0.4663	0.4873	0.084*
H11B	0.2455	0.5592	0.5265	0.084*
C12	0.1656 (5)	0.5381 (4)	0.3244 (5)	0.0678 (16)
H12A	0.1511	0.4814	0.2645	0.081*
H12B	0.2351	0.5812	0.3076	0.081*
C13	0.0281 (6)	0.5950 (4)	0.2946 (6)	0.0682 (16)
H13A	−0.0395	0.5518	0.3142	0.082*
H13B	0.0441	0.6515	0.3550	0.082*
C14	−0.0361 (5)	0.6330 (4)	0.1532 (5)	0.0625 (14)
H14A	−0.0494	0.5774	0.0915	0.075*
H14B	0.0280	0.6797	0.1341	0.075*
C15	−0.1783 (5)	0.6848 (4)	0.1306 (6)	0.0720 (17)
H15A	−0.2167	0.7062	0.0392	0.108*
H15B	−0.1649	0.7416	0.1886	0.108*
H15C	−0.2420	0.6388	0.1498	0.108*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.076 (2)	0.0392 (18)	0.0221 (15)	−0.0146 (16)	0.0010 (14)	−0.0055 (14)
N1	0.078 (3)	0.0264 (17)	0.0171 (18)	−0.0194 (18)	0.0054 (16)	0.0008 (14)
N2	0.078 (3)	0.0291 (19)	0.0170 (16)	−0.0129 (18)	−0.0015 (16)	0.0016 (14)
C1	0.095 (4)	0.030 (2)	0.029 (2)	−0.015 (2)	−0.007 (2)	−0.0035 (18)
C2	0.111 (5)	0.030 (3)	0.040 (3)	0.003 (3)	−0.027 (3)	−0.006 (2)
C3	0.058 (4)	0.047 (3)	0.135 (6)	0.014 (3)	−0.028 (4)	−0.050 (4)
C4	0.049 (3)	0.098 (5)	0.187 (8)	−0.013 (3)	0.020 (4)	−0.107 (6)
C5	0.053 (3)	0.079 (4)	0.116 (5)	−0.008 (3)	0.023 (3)	−0.073 (4)
C6	0.058 (3)	0.022 (2)	0.037 (2)	0.011 (2)	−0.011 (2)	−0.0064 (17)
C7	0.062 (3)	0.0192 (18)	0.020 (2)	0.0028 (19)	−0.0043 (19)	0.0021 (15)
C8	0.051 (3)	0.0231 (19)	0.023 (2)	0.003 (2)	−0.0046 (16)	0.0011 (16)
C9	0.067 (3)	0.026 (2)	0.0139 (19)	−0.003 (2)	−0.0043 (18)	0.0042 (16)
C10	0.122 (5)	0.048 (3)	0.029 (2)	−0.047 (3)	0.021 (3)	0.004 (2)
C11	0.095 (4)	0.074 (4)	0.046 (3)	−0.050 (4)	0.029 (3)	−0.005 (3)
C12	0.062 (3)	0.087 (4)	0.058 (3)	−0.041 (3)	0.025 (2)	0.011 (3)
C13	0.059 (3)	0.084 (4)	0.071 (4)	−0.044 (3)	0.035 (3)	−0.026 (3)
C14	0.041 (3)	0.076 (4)	0.076 (4)	−0.021 (3)	0.027 (3)	−0.008 (3)
C15	0.048 (3)	0.073 (4)	0.104 (4)	−0.025 (3)	0.037 (3)	−0.044 (3)

Geometric parameters (Å, º)

O1—C9	1.336 (5)	C8—H8	0.9300
O1—H1A	0.87 (5)	C10—C11	1.524 (8)
N1—C9	1.355 (5)	C10—H10A	0.9700
N1—N2	1.385 (4)	C10—H10B	0.9700
N1—C10	1.448 (6)	C11—C12	1.515 (7)
N2—C7	1.336 (6)	C11—H11A	0.9700
C1—C2	1.392 (7)	C11—H11B	0.9700
C1—C6	1.392 (6)	C12—C13	1.522 (8)
C1—H1	0.9300	C12—H12A	0.9700
C2—C3	1.377 (9)	C12—H12B	0.9700
C2—H2	0.9300	C13—C14	1.510 (7)
C3—C4	1.351 (9)	C13—H13A	0.9700
C3—H3	0.9300	C13—H13B	0.9700
C4—C5	1.367 (8)	C14—C15	1.540 (7)
C4—H4	0.9300	C14—H14A	0.9700
C5—C6	1.371 (7)	C14—H14B	0.9700
C5—H5	0.9300	C15—H15A	0.9600
C6—C7	1.470 (5)	C15—H15B	0.9600
C7—C8	1.407 (5)	C15—H15C	0.9600
C8—C9	1.359 (6)
C9—O1—H1A	110 (3)	C11—C10—H10A	108.9
C9—N1—N2	110.1 (3)	N1—C10—H10B	108.9
C9—N1—C10	128.2 (3)	C11—C10—H10B	108.9
N2—N1—C10	121.6 (3)	H10A—C10—H10B	107.7
C7—N2—N1	105.3 (3)	C12—C11—C10	114.7 (5)
C2—C1—C6	119.8 (6)	C12—C11—H11A	108.6
C2—C1—H1	120.1	C10—C11—H11A	108.6
C6—C1—H1	120.1	C12—C11—H11B	108.6
C3—C2—C1	120.7 (5)	C10—C11—H11B	108.6
C3—C2—H2	119.6	H11A—C11—H11B	107.6
C1—C2—H2	119.6	C11—C12—C13	112.1 (5)
C4—C3—C2	118.7 (5)	C11—C12—H12A	109.2
C4—C3—H3	120.7	C13—C12—H12A	109.2
C2—C3—H3	120.7	C11—C12—H12B	109.2
C3—C4—C5	121.5 (7)	C13—C12—H12B	109.2
C3—C4—H4	119.3	H12A—C12—H12B	107.9
C5—C4—H4	119.3	C14—C13—C12	115.8 (4)
C4—C5—C6	121.4 (5)	C14—C13—H13A	108.3
C4—C5—H5	119.3	C12—C13—H13A	108.3
C6—C5—H5	119.3	C14—C13—H13B	108.3
C5—C6—C1	118.0 (4)	C12—C13—H13B	108.3
C5—C6—C7	119.2 (4)	H13A—C13—H13B	107.4
C1—C6—C7	122.8 (4)	C13—C14—C15	112.1 (4)
N2—C7—C8	110.7 (4)	C13—C14—H14A	109.2
N2—C7—C6	122.4 (3)	C15—C14—H14A	109.2
C8—C7—C6	126.7 (4)	C13—C14—H14B	109.2
C9—C8—C7	105.6 (4)	C15—C14—H14B	109.2
C9—C8—H8	127.2	H14A—C14—H14B	107.9
C7—C8—H8	127.2	C14—C15—H15A	109.5
O1—C9—N1	118.6 (4)	C14—C15—H15B	109.5
O1—C9—C8	133.2 (4)	H15A—C15—H15B	109.5
N1—C9—C8	108.2 (3)	C14—C15—H15C	109.5
N1—C10—C11	113.5 (4)	H15A—C15—H15C	109.5
N1—C10—H10A	108.9	H15B—C15—H15C	109.5

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1A···N2^i	0.86 (5)	1.80 (5)	2.658 (5)	176 (5)

Symmetry code: (i) x, −y+1, z−1/2.