4,5-Di­hydro-3-methyl-5-(4-methyl­phenyl)-1H-pyrazole-1-carboxamidinium acetate acetone hemisolvate

The X-ray structure analysis of the unexpected product of the reaction between 4-(4-methyl­phenyl)­but-3-en-2-one and amino­guanidine revealed the title compound, C₁₂H₁₇N₄⁺·C₂H₃O₂⁻·0.5C₃H₆O, consisting of a protonated amidine moiety joined to a substituted pyrazoline ring at the N1 atom. The amidine group is protonated and the positive charge is delocalized over the three C—N bonds in a similar manner to that found in guanidinium salts. The amidinium moiety of the cation is linked to the acetate anions through four N—H...O hydrogen bonds, with N...O distances of 2.749 (4), 2.848 (4), 2.904 (4) and 2.911 (4) Å. The pyrazoline ring adopts a flattened envelope conformation and the substituted phenyl ring is oriented perpendicular to the attached heterocycle. The acetone solvate molecule lies across a twofold rotation axis.

S1. Comment

Recently, aminoguanidine has been reported to be a potent inhibitor of nitric oxide synthase (Griffith & Gross, 1996). The remarkable biological activity of this simple nitrogen base prompted us to direct our research interest towards its derivatives, particularly heterocyclic congeners. For this purpose, we re-examined the literature data on cyclocondensation of aminoguanidine with some α,β-unsaturated ketones, (1). However, under neutral conditions, the compounds obtained by us showed certain spectral dissimilarities when compared with expected 1,2,4-triazines, (2) (Neunhoeffer, 1984). We had, therefore, to take into account three other possible candidates, (3)–(5), of which the pyrazole-1-carboximidamide, (3), was deduced as the most probable reaction product (Světlík & Sallai, 2002). To support our structural assignment, based predominantly on the mass spectral behaviour, and, at the same time, to obtain detailed structural data for subsequent structure-activity relationship study, we selected one of the unexpectedly formed heterocycles, namely the title compound, (3 b), for an X-ray structure analysis.

The asymmetric unit of (3 b) contains a protonated amidinium molecule, one acetate anion and half an acetone molecule (Fig. 1). The latter molecule occupies a site of C₂ symmetry with the C═O bond lying on the twofold axis along (0,y,1/4). The anomalous product of the aforementioned reaction has the structure (3), i.e. it consists of a substituted pyrazoline ring and a protonated amidine function attached to atom N1. The overall conformation of the molecule can also be inferred from Fig. 1. Calculation of the least-squares plane has shown that the pyrazoline ring adopts a flat-envelope conformation, with atom C5 on the flap; the deviation of the out-of-plane atom from the mean plane of the remaining four atoms [r.m.s. deviation 0.001 (2) Å] is 0.209 (6) Å. The 4-methylphenyl group occupies a pseudo-axial position and, as a result, is approximately perpendicular to the mean plane of the pyrazoline ring [dihedral angle 87.4 (2)°]. The phenyl ring is rotated about the exocyclic C5—C6 bond in such a manner that the ring nearly bisects the heterocyclic ring [torsion angle C4—C5—C6—C7 - 62.9 (5)°]. Selected bond lengths and angles in the cation are listed in Table 1. It has been reported (Krishna et al., 1999) that the N—N bond length in the pyrazoline ring varies in a wide range from 1.385 (4) to 1.234 (8) Å, depending on the substituents bonded to the N atoms; accordingly, the length of the adjacent C═N bond ranges from 1.288 (4) to 1.461 (8) Å. This is caused by a varying degree of conjugation within the π-electron portion of the pyrazoline ring which is sensitively affected by the nature of substituent(s) bonded to the atoms of the π system. The N1—N2 bond length of 1.391 (4) Å found in (3 b) further extends this range, approximating a pure single bond (1.41 Å; Burke-Laing & Laing, 1976). Similarly, the corresponding N2═C3 bond [1.274 (4) Å] has pure double-bond character (1.27 Å). That the lone-pair electrons on atom N1 are delocalized through conjugation with the amidine group rather than the N2═ C3 double bond is also seen in the N1—C14 bond length [1.324 (5) Å], which is intermediate between the single and double bond and equivalent to the two C—N bonds in the amidine moiety. Similar C—N bond distances have also been found in a number of inorganic salts containing the guanidinium cation (see, for example, Katrusiak & Szafranski, 1994). Other bond distances and angles in the remaining parts of the molecule are normal and close to those generally expected. The positive charge of the protonated molecule is neutralized by the acetate anion. All of the four potential hydrogen-bond donors are actually involved in hydrogen bonding with the acetate anions (see Table 2 for details). As all the hydrogen-bond donors are utilized in the hydrogen-bond interactions with the acetate anions, the solvent acetone molecule is rather loosely packed by van der Waals interactions.

S2. Experimental

The title compound, (3 b), was synthesized by cyclocondensation of 4-(4-methylphenyl)but-3-en-2-one with aminoguanidine hydrogencarbonate, as described elsewhere (Světlík & Sallai, 2002). Briefly, a suspension of both reactants (10 mmol each) in n-butanol (30 ml) was refluxed with stirring for 3 h. The resulting solution was concentrated on a vacuum rotary evaporator. The syrupy residue obtained was dissolved in ethyl acetate (10 ml) and then left to stand at room temperature. After isolation of a by-product, the required amidine precipitated from the mother liquor (0.42 g, 20% yield, m.p. 493–494 K). Single crystals were obtained by recrystallization from an ethyl acetate–acetone (1:1) solution.

S3. Refinement

All H atoms, except for those in the acetone molecule, were located from difference maps, and were susequently treated as riding atoms with C—H distances in the range 0.93–0.97 Å and N—H distances of 0.86 Å.

Computing details

Data collection: Syntex Software (Syntex, 1973); cell refinement: Syntex Software; data reduction: XP21 (Pavelčík, 1987); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97.

Figures

Fig. 1. A view of the cation of the title compound with the atom-numbering scheme. Displacement ellipsoids are shown at 35% probability levels. H atoms are shown as circles of arbitrary radii. [Symmetry code: (i) -x, y, 0.5 - z].

4,5-Dihydro-3-methyl-5-(4-methylphenyl)-1H-pyrazole-1-carboxamidinium acetate acetone hemisolvate

Crystal data

C12H17N4^+·C2H3O2^−·0.5C3H6O	Dx = 1.239 Mg m^−3 Dm = 1.24 (1) Mg m^−3 Dm measured by flotation in bromoform/c-hexane
Mr = 305.38	Melting point: 494 K
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 27.679 (11) Å	Cell parameters from 15 reflections
b = 8.126 (4) Å	θ = 9–20°
c = 18.776 (9) Å	µ = 0.09 mm^−1
β = 129.15 (6)°	T = 293 K
V = 3275 (3) Å^3	Prism, colourless
Z = 8	0.35 × 0.30 × 0.25 mm
F(000) = 1312

Data collection

Syntex P21 diffractometer	Rint = 0.043
Radiation source: fine-focus sealed tube	θmax = 25.1°, θmin = 1.9°
Graphite monochromator	h = −24→32
θ/2θ scans	k = 0→9
2972 measured reflections	l = −21→0
2883 independent reflections	2 standard reflections every 98 reflections
1600 reflections with I > 2σ(I)	intensity decay: 2%

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.073	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.229	H-atom parameters constrained
S = 1.00	w = 1/[σ^2(Fo^2) + (0.1372P)^2 + 0.7484P] where P = (Fo^2 + 2Fc^2)/3
2883 reflections	(Δ/σ)max = 0.001
204 parameters	Δρmax = 0.27 e Å^−3
0 restraints	Δρmin = −0.39 e Å^−3

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

	x	y	z	Uiso*/Ueq
N1	0.17743 (14)	0.2915 (3)	0.50412 (19)	0.0454 (7)
N2	0.16536 (13)	0.2725 (3)	0.42057 (19)	0.0461 (7)
C3	0.14613 (16)	0.1257 (4)	0.3935 (2)	0.0479 (9)
C4	0.14301 (18)	0.0254 (5)	0.4563 (3)	0.0573 (10)
H4A	0.1743	−0.0608	0.4850	0.069*
H4B	0.1022	−0.0243	0.4239	0.069*
C5	0.15579 (17)	0.1497 (4)	0.5273 (3)	0.0492 (9)
H5	0.1895	0.1104	0.5895	0.059*
C6	0.09914 (15)	0.1907 (4)	0.5182 (2)	0.0425 (8)
C7	0.0477 (2)	0.2658 (5)	0.4397 (3)	0.0692 (12)
H7	0.0490	0.2960	0.3932	0.083*
C8	−0.0058 (2)	0.2968 (5)	0.4292 (3)	0.0696 (12)
H8	−0.0396	0.3468	0.3756	0.083*
C9	−0.01002 (18)	0.2559 (4)	0.4956 (3)	0.0549 (10)
C10	0.0416 (2)	0.1807 (5)	0.5734 (3)	0.0635 (11)
H10	0.0403	0.1508	0.6200	0.076*
C11	0.09462 (18)	0.1488 (5)	0.5842 (2)	0.0552 (10)
H11	0.1281	0.0975	0.6376	0.066*
C12	0.1278 (2)	0.0647 (5)	0.3048 (3)	0.0699 (12)
H12A	0.0835	0.0491	0.2621	0.105*
H12B	0.1483	−0.0381	0.3146	0.105*
H12C	0.1398	0.1437	0.2805	0.105*
C13	−0.0670 (2)	0.2871 (6)	0.4847 (4)	0.0774 (13)
H13A	−0.0792	0.4001	0.4680	0.116*
H13B	−0.0589	0.2645	0.5415	0.116*
H13C	−0.1000	0.2170	0.4374	0.116*
C14	0.20306 (15)	0.4303 (4)	0.5505 (2)	0.0403 (8)
N3	0.21865 (13)	0.4504 (4)	0.63275 (19)	0.0498 (8)
H3A	0.2348	0.5417	0.6617	0.060*
H3B	0.2126	0.3720	0.6571	0.060*
N4	0.21280 (13)	0.5522 (3)	0.51449 (18)	0.0496 (8)
H4C	0.2025	0.5415	0.4609	0.059*
H4D	0.2295	0.6423	0.5446	0.059*
C15	0.21155 (16)	0.3530 (4)	0.8083 (2)	0.0449 (9)
O1	0.23153 (12)	0.2668 (3)	0.77709 (17)	0.0539 (7)
O2	0.21850 (15)	0.3199 (3)	0.87874 (18)	0.0716 (9)
C16	0.1751 (2)	0.5045 (5)	0.7577 (3)	0.0626 (11)
H16A	0.1391	0.4756	0.6965	0.094*
H16B	0.2006	0.5796	0.7550	0.094*
H16C	0.1620	0.5557	0.7891	0.094*
C17	0.0000	0.6922 (10)	0.2500	0.085 (2)
O3	0.0000	0.8463 (8)	0.2500	0.161 (3)
C18	0.0542 (3)	0.6072 (8)	0.2821 (5)	0.116 (2)
H18A	0.0876	0.6841	0.3064	0.174*
H18B	0.0473	0.5469	0.2325	0.174*
H18C	0.0649	0.5321	0.3296	0.174*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0565 (18)	0.0421 (16)	0.0458 (16)	−0.0134 (14)	0.0362 (15)	−0.0071 (13)
N2	0.0495 (17)	0.0458 (18)	0.0436 (16)	−0.0062 (14)	0.0297 (15)	−0.0072 (13)
C3	0.049 (2)	0.044 (2)	0.051 (2)	−0.0058 (17)	0.0311 (18)	−0.0075 (17)
C4	0.060 (2)	0.045 (2)	0.068 (3)	−0.0066 (18)	0.041 (2)	−0.0076 (18)
C5	0.050 (2)	0.042 (2)	0.053 (2)	−0.0043 (16)	0.0320 (18)	0.0030 (16)
C6	0.047 (2)	0.0366 (18)	0.0429 (19)	−0.0055 (15)	0.0277 (17)	0.0000 (15)
C7	0.074 (3)	0.083 (3)	0.069 (3)	0.019 (2)	0.054 (2)	0.031 (2)
C8	0.065 (3)	0.082 (3)	0.068 (3)	0.020 (2)	0.045 (2)	0.030 (2)
C9	0.054 (2)	0.047 (2)	0.069 (3)	−0.0031 (18)	0.042 (2)	−0.0012 (19)
C10	0.070 (3)	0.080 (3)	0.058 (2)	0.003 (2)	0.049 (2)	0.008 (2)
C11	0.055 (2)	0.063 (3)	0.0399 (19)	−0.0011 (19)	0.0267 (18)	0.0051 (18)
C12	0.083 (3)	0.058 (3)	0.065 (3)	−0.012 (2)	0.045 (2)	−0.020 (2)
C13	0.073 (3)	0.077 (3)	0.103 (4)	−0.001 (2)	0.065 (3)	0.004 (3)
C14	0.0409 (18)	0.045 (2)	0.0382 (18)	−0.0037 (15)	0.0263 (15)	0.0013 (15)
N3	0.0664 (19)	0.0478 (18)	0.0451 (16)	−0.0100 (15)	0.0400 (15)	−0.0037 (14)
N4	0.068 (2)	0.0448 (17)	0.0385 (15)	−0.0167 (15)	0.0348 (15)	−0.0087 (13)
C15	0.053 (2)	0.047 (2)	0.0383 (19)	−0.0004 (17)	0.0306 (17)	−0.0006 (15)
O1	0.0665 (16)	0.0561 (16)	0.0494 (14)	0.0191 (13)	0.0415 (14)	0.0113 (12)
O2	0.120 (3)	0.0592 (17)	0.0576 (17)	0.0308 (16)	0.0662 (18)	0.0195 (14)
C16	0.084 (3)	0.058 (2)	0.064 (2)	0.021 (2)	0.055 (2)	0.017 (2)
C17	0.095 (6)	0.079 (5)	0.076 (5)	0.000	0.052 (4)	0.000
O3	0.097 (4)	0.104 (5)	0.238 (9)	0.000	0.085 (5)	0.000
C18	0.103 (4)	0.126 (5)	0.140 (5)	0.045 (4)	0.087 (4)	0.033 (4)

Geometric parameters (Å, º)

N1—C14	1.324 (4)	C12—H12B	0.9600
N1—N2	1.391 (4)	C12—H12C	0.9600
N1—C5	1.485 (4)	C13—H13A	0.9600
N2—C3	1.274 (4)	C13—H13B	0.9600
C3—C4	1.481 (5)	C13—H13C	0.9600
C3—C12	1.486 (5)	C14—N4	1.319 (4)
C4—C5	1.526 (5)	C14—N3	1.326 (4)
C4—H4A	0.9700	N3—H3A	0.8600
C4—H4B	0.9700	N3—H3B	0.8600
C5—C6	1.503 (5)	N4—H4C	0.8600
C5—H5	0.9800	N4—H4D	0.8600
C6—C11	1.365 (5)	C15—O2	1.240 (4)
C6—C7	1.387 (5)	C15—O1	1.245 (4)
C7—C8	1.386 (6)	C15—C16	1.492 (5)
C7—H7	0.9300	C16—H16A	0.9600
C8—C9	1.364 (6)	C16—H16B	0.9600
C8—H8	0.9300	C16—H16C	0.9600
C9—C10	1.383 (6)	C17—O3	1.252 (9)
C9—C13	1.480 (6)	C17—C18^i	1.395 (6)
C10—C11	1.374 (5)	C17—C18	1.395 (6)
C10—H10	0.9300	C18—H18A	0.9600
C11—H11	0.9300	C18—H18B	0.9600
C12—H12A	0.9600	C18—H18C	0.9600
C14—N1—N2	118.9 (3)	C3—C12—H12B	109.5
C14—N1—C5	128.0 (3)	H12A—C12—H12B	109.5
N2—N1—C5	113.0 (3)	C3—C12—H12C	109.5
C3—N2—N1	107.3 (3)	H12A—C12—H12C	109.5
N2—C3—C4	114.7 (3)	H12B—C12—H12C	109.5
N2—C3—C12	121.4 (3)	C9—C13—H13A	109.5
C4—C3—C12	123.9 (3)	C9—C13—H13B	109.5
C3—C4—C5	103.5 (3)	H13A—C13—H13B	109.5
C3—C4—H4A	111.1	C9—C13—H13C	109.5
C5—C4—H4A	111.1	H13A—C13—H13C	109.5
C3—C4—H4B	111.1	H13B—C13—H13C	109.5
C5—C4—H4B	111.1	N4—C14—N1	120.1 (3)
H4A—C4—H4B	109.0	N4—C14—N3	118.9 (3)
N1—C5—C6	112.3 (3)	N1—C14—N3	121.0 (3)
N1—C5—C4	99.9 (3)	C14—N3—H3A	120.0
C6—C5—C4	113.4 (3)	C14—N3—H3B	120.0
N1—C5—H5	110.3	H3A—N3—H3B	120.0
C6—C5—H5	110.3	C14—N4—H4C	120.0
C4—C5—H5	110.3	C14—N4—H4D	120.0
C11—C6—C7	117.0 (4)	H4C—N4—H4D	120.0
C11—C6—C5	121.9 (3)	O2—C15—O1	124.4 (3)
C7—C6—C5	121.1 (3)	O2—C15—C16	116.4 (3)
C8—C7—C6	121.2 (4)	O1—C15—C16	119.2 (3)
C8—C7—H7	119.4	C15—C16—H16A	109.5
C6—C7—H7	119.4	C15—C16—H16B	109.5
C9—C8—C7	121.7 (4)	H16A—C16—H16B	109.5
C9—C8—H8	119.2	C15—C16—H16C	109.5
C7—C8—H8	119.2	H16A—C16—H16C	109.5
C8—C9—C10	116.5 (4)	H16B—C16—H16C	109.5
C8—C9—C13	122.1 (4)	O3—C17—C18^i	119.7 (4)
C10—C9—C13	121.4 (4)	O3—C17—C18	119.7 (4)
C11—C10—C9	122.3 (4)	C18^i—C17—C18	120.7 (8)
C11—C10—H10	118.9	C17—C18—H18A	109.5
C9—C10—H10	118.9	C17—C18—H18B	109.5
C6—C11—C10	121.4 (4)	H18A—C18—H18B	109.5
C6—C11—H11	119.3	C17—C18—H18C	109.5
C10—C11—H11	119.3	H18A—C18—H18C	109.5
C3—C12—H12A	109.5	H18B—C18—H18C	109.5
C14—N1—N2—C3	174.4 (3)	C4—C5—C6—C7	−62.9 (5)
C5—N1—N2—C3	−8.6 (4)	C11—C6—C7—C8	0.1 (6)
N1—N2—C3—C4	−0.3 (4)	C5—C6—C7—C8	176.9 (4)
N1—N2—C3—C12	178.9 (3)	C6—C7—C8—C9	0.4 (7)
N2—C3—C4—C5	8.3 (4)	C7—C8—C9—C10	−0.5 (7)
C12—C3—C4—C5	−170.8 (3)	C7—C8—C9—C13	−179.4 (4)
C14—N1—C5—C6	69.1 (4)	C8—C9—C10—C11	0.2 (6)
N2—N1—C5—C6	−107.6 (3)	C13—C9—C10—C11	179.1 (4)
C14—N1—C5—C4	−170.4 (3)	C7—C6—C11—C10	−0.4 (6)
N2—N1—C5—C4	12.9 (4)	C5—C6—C11—C10	−177.2 (4)
C3—C4—C5—N1	−11.7 (4)	C9—C10—C11—C6	0.3 (6)
C3—C4—C5—C6	108.0 (3)	N2—N1—C14—N4	4.7 (5)
N1—C5—C6—C11	−133.9 (3)	C5—N1—C14—N4	−171.8 (3)
C4—C5—C6—C11	113.8 (4)	N2—N1—C14—N3	−176.1 (3)
N1—C5—C6—C7	49.4 (5)	C5—N1—C14—N3	7.3 (5)

Symmetry code: (i) −x, y, −z+1/2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3A···O1	0.86	2.04	2.911 (4)	176
N3—N3B···O1^ii	0.86	2.14	2.904 (4)	149
N4—H4C···O1^iii	0.86	2.16	2.848 (4)	136
N4—H4D···O1^ii	0.86	1.90	2.749 (4)	169

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