X-ray supramolecular structure, NMR spectroscopy and synthesis of 3-methyl-1-phenyl-1H-chromeno[4,3-c]pyrazol-4-ones formed by the unexpected cyclization of 3-[1-(phenyl-hydrazono)ethyl]-chromen-2-ones.

The molecular structures of nine 3-methyl-1-phenyl-1H-chromeno[4,3-c]pyrazol-4-one isomers, obtained by the oxidative cyclization of the corresponding 1-phenylhydrazono chromen-2-ones with copper acetate as catalyst, are reported. The molecular and supramolecular structures of the 8-chloro, 8-bromo- and 8-nitro isomers 2b-d, were established by X-ray diffraction. The halogenated isomers 2b and 2c are isomorphs, they crystallize as a triclinic system, space group P-1 with two molecules in the asymmetric unit. Compound 2d crystallizes as a monoclinic system, space group P2₁/m with two molecules in the unit cell. The 1-phenyl ring [Cg(4)] is almost perpendicularly positioned to the chromene-pyrazole ring system. This conformation is in agreement with the anisotropic NMR shielding effect exerted by the phenyl ring over H-9 in solution. The supramolecular architecture is almost controlled by C-H···A (A = O, p) and face to face p-stacking interactions. The observed p-stacking trend between chromene and pyrazole rings is given by the overlapping between the best donor and acceptor rings in each compound.

1. Introduction

Pyrazole and its derivatives are shown to possess important biological and pharmaceuticalactivities [1,2] such as antimicrobial [3,4], antiviral [5,6], anxiolytic [7,8] and anti-inflammatory [4,9] activities. They are also useful in agrochemical industry as herbicides [10,11] and insecticides [12].

The 1-phenylchromeno[4,3-c]pyrazol-4-ones are important n class="Chemical">pyrazole derivatives which have been used for the synthesis of inmunomodulatory drugs because of their interaction with the benzodiazepine central receptor [13]. Several methods of synthesis have been reported starting from arylidenechromones and hydrazine in basic media [14,15]; 3-CN-4-[(o-hydroxy)phenyl]-1-phenyl-3-methylpyrazole in ethanediol [16]; 4-substituted with –OH and –Cl 1-(phenylhydrazono)-chromen-2-ones by cyclization in acidic media [17]. To the best of our knowledge, this cyclization is not expected in the absence of a 4-positioned good leaving group, and the closest reported approach is the cyclization of 6-chloro-3-{1-[(2,4,6-trichlorophenyl)-hydrazono]-ethyl}-chromen-2-one in the presence of equimolar quantities of SbCl5 to obtain a 3-methyl-1-(2,4,6-trichlorophenyl)-1H-chromeno-[4,3-c]pyrazol-4-one similar to 2a in 86% yield [18] and the reaction of 1-(chloro(thiophen-2-yl)methylene)-2-phenylhydrazine with coumarin at reflux in chloroform and triethylamine to yield 1-phenyl-3-thiophen-2-yl-1H-chromeno[4,3-c]pyrazol-4-one [19]. In addition, it is worth mentioning that there are six related structures deposited in the CSD (Version of November 2008) [20] but only one discussed in the literature.

In this contribution the synthesis of 1-phenyl-chromeno[4,3-c]pyrazol-4-ones 2a-i through the oxidative cyclization of 3-(phenyl-hydrazono)-chromen-2-ones 1a-i with copper acetate as catalyst is reported (Scheme 1). The structures in solution by NMR as well as the molecular and supramolecular structures in the solid state, by monocrystal X-ray diffraction, are discussed.

Scheme 1

Synthesis of 3-methyl-1-phenyl-1H-chromeno[4,3-c]pyrazol-4-ones 2a-i starting form 3-[1-(phenyl-hydrazono)-ethyl]-chromen-2-ones 1a-i.

2. Results and Discussion

2.1. Synthesis and Molecular Structure in Solution

In our efforts to crystallize hydrazone 1a from a saturated n class="Chemical">chloroform solution, crystals of 3-methyl-1-phenyl-1H-chromeno[4,3-c]pyrazol-4-one 2a were spontaneously formed instead in 30% yield at RT. It is worthy to note that the cyclization reaction of 1a is not expected, because of the absence of a 4-positioned good leaving group to allow pyrazole ring formation. To ascertain the scope and limitation of this transformation, several 3-(phenyl-hydrazono)-chromen-2-ones 1b-i were tested but cyclization did not proceed under the same conditions as for 1a. This result lead us to use Cu(CH3COO)2·H2O as catalyst, since some examples of copper-catalyzed oxidative amination of alkynes [21] and azoles [22] via CH and NH coupling have recently been reported. Then, compounds 2a-i were prepared in poor to good yields (50–83%), starting from the corresponding 3-[1-(phenyl-hydrazono)-ethyl]-chromen-2-ones 1a-i, using Cu(CH3COO)2·H2O as catalyst in 20:1 weight ratio under mild conditions. In comparison with reported methods, starting from 4-hydroxybenzopyrano-arylhydrazones, the yields are lower or similar for 2a (76%) [17] and 2b (39%) [15], but in the case of 2c (78%) and 2d (83%) [23] they are significantly enhanced by the use of the copper catalyst.

The reaction should proceed by a simple intramolecular conjugate addition of the n class="Gene">Ph-N to the α,β-unsaturated–C=N+ system, through the intermediate A, and the subsequent oxidation of the resulting dihydro-pyrazolone B (Scheme 2). This proposal is supported on similar reactions reported in acid media [24,25]. The formation of the key intermediate A’ would be disfavored either by electro withdrawing (W) or by electrodonating (D) substituents, which would explain the necessary aid of the copper catalyst (Scheme 3).

Scheme 2

Proposed mechanism of reaction.

Scheme 3

Resonance structures of 6-substituted-3-[1-(phenyl-hydrazono)-ethyl]-chromen-2-ones 1a-i with electrowithdrawing (W) or electrodonor (D) groups.

Several differences in the 1H- and n class="Chemical">13C-NMR spectra appear as a consequence of the cyclization. Selected NMR and IR data are listed in Table 1 and Table 2 for 1a-i and 2a-i, respectively. The 1H-NMR spectra of compounds 2a-i is characterized by the loss of the H-4 signal, usually appearing as a singlet at δ 7.98–8.17, in the starting compounds 1a-i. In addition, the chemical shift of H-9 in 2a-i appears at δ 6.62–8.02, more shielded than the former H-5 (δ 6.97–8.51) in 1a-i, because of the anisotropic NMR shielding effect exerted by the phenyl group which should be almost perpendicular to the 1-phenyl-chromeno[4,3-c]pyrazol-4-one ring system in compounds 2a-f. The 13C chemical shift of C-3a appears at 106–107 ppm in compounds 2a-i, whereas the former C-3, in the starting hydrazones 1a-i, is at 127.8–130.6 ppm. Subtle shielding is also observed for C-9a (former C-10) by 7.0 ppm, in agreement with the aromatic character of the newly formed pyrazole ring. The chemical shift of C-9b (former C-4) remains almost the same even when in this position was performed the ring closure.

Table 1

Selected NMR and IR spectroscopic data for hydrazones 1a-i.

	δ 1H		δ 13C				ν/cm−1
Comp.	H-4	H-5	C-2	C-3	C-4	C-10	CO
1a	8.16	7.81	160.2	127.9	139.8	119.9	1695, 1596
1b	8.17	7.97	159.2	128.2	137.8	119.5	1703, 1598
1c	8.15	8.08	159.1	128.3	137.7	116.1	1704, 1597
1d	8.40	8.84	159.2	130.6	137.7	119.9	1726, 1604
1e	7.98	6.97	160.9	127.9	139.7	120.1	1698, 1574
1f	8.02	7.06	160.2	127.9	140.0	120.4	1700, 1601
1g	7.95	7.34	156.3	128.8	138.3	116.9	1713, 1599
1h	7.95	7.51	159.2	129.2	137.6	121.6	1707, 1530
1i	7.96	7.41	159.0	129.7	137.6	121.6	1709, 1533

Table 2

Selected NMR and IR spectroscopic data for pyrazoles 2a-i.

	δ 1H	δ 13C				ν/cm−1
Comp.	H-9	C-4	C-3a	C-9a	C-9b	CO
2a	7.09	158.3	106.5	112.0	141.9	1726
2b	7.03	157.6	106.8	113.1	140.7	1743
2c	7.16	157.6	106.8	113.7	140.6	1742
2d	8.02	156.9	106.8	112.4	143.6	1756
2e	6.50	158.4	106.7	112.1	141.9	1734
2f	6.65	157.6	106.6	112.7	142.1	1743
2g	6.72	156.7	106.8	113.7	140.1	1744
2h	6.90	156.2	106.8	112.6	140.2	1749
2i	6.90	156.2	106.8	114.0	140.2	1750

The saturation of the Me frequency in 1a (δ 2.20, s) gives a NOE effect on proton H-4 (δ 8.16, s) and n class="Chemical">NH proton (δ 9.43, s), suggesting an E configuration for the C=N double bond and thus the predominance in solution of the rotamer I (Scheme 4). Thus the transformation of 1a into 2a implies the breaking of the double –C=N– bond to a single –C–N– to allow the location of the atoms in the proper place for cyclization in agreement with the above mentioned copper-catalyzed oxidative amination.

Scheme 4

Rotamers I-IV in solution and isomerization from E to Z in acid media.

2.2. Molecular and Supramolecular Structure in Solid State

1-Phenyl-chromeno[4,3-c]pyrazol-4-ones 2b-d were crystallized from saturated n class="Chemical">DMF solutions. The halogenated isomers 2b,c crystallize as a triclinic system, space group P-1 with two molecules in the asymmetric unit. Compound 2d crystallizes as a monoclinic system, space group P21/m with two molecules in the unit cell. A summary of bond lengths and angles are listed in Table 3 and crystal data and structure refinement for 2b-d are listed in Table 4. As in other coumarin derivatives, the replacement of Cl by Br does not alter the crystal packing [26]. All the atoms of pyrazole and chromenone rings lie in a single plane within the limits of experimental error. The 1-phenyl ring in compounds 2b-d is sterically hindered and appears twisted by 71.9(2)º, 74.7(5)º and 92.1(2)º, respectively, from the three ring fused coplanar chromeno[4,3-c]pyrazol-4-one system in agreement with the conformation observed in solution (vide supra). The torsion angle between both planes is very close to that observed for 1-phenyl-1H-chromeno[4,3-c]pyrazol-4-one of 73.1(6)º [27]. However, in compound 2d the 1-phenyl ring [Cg(4)] is almost perpendicularly positioned, thus a symmetry plane cut the molecule through its equatorial plane and only one half of the phenyl ring is observed. This conformation is in agreement with the observed anisotropic NMR shielding effect exerted by the phenyl ring over H-9 in solution.

Table 3

Selected bond lengths and angles from X-ray data of compounds 2b-d.

	2b X = Cl	2c X = Br	2d X = NO2
Atoms	Bond lengths (Å)
X(8)―C(8)	1.732(2)	1.894(4)	1.466(2)
O(4)―C(4)	1.200(2)	1.197(6)	1.189(2)
O(5)―C(4)	1.385(2)	1.385(6)	1.404(2)
O(5)―C(5A)	1.382(2)	1.379(5)	1.374(2)
N(1)―N(2)	1.376(2)	1.374(5)	1.379(2)
N(1)―C(9B)	1.346(2)	1.353(5)	1.345(2)
N(1)―C(10)	1.433(2)	1.428(6)	1.433(2)
N(2)―C(3)	1.321(2)	1.315(6)	1.315(2)
C(3)―C(3A)	1.408(3)	1.400(7)	1.408(3)
C(3A)―C(4)	1.435(3)	1.441(6)	1.441(3)
C(3A)―C(9B)	1.384(2)	1.378(5)	1.380(2)
C(5A)―C(9A)	1.402(3)	1.389(6)	1.403(3)
C(9A)―C(9B)	1.437(3)	1.438(5)	1.442(2)
O(8B)―N(8)			1.195(3)
O(8A)―N(8)			1.204(2)
	Bond angles (º)
C(4)―O(5)―C(5A)	123.60(15)	123.8(4)	124.12(15)
N(2)―N(1)―C(9B)	111.82(14)	111.3(3)	111.53(12)
N(2)―N(1)―C(10)	118.91(15)	119.8(4)	121.02(14)
C(9B)―N(1)―C(10)	129.18(15)	128.9(3)	127.44(14)
N(1)―N(2)―C(3)	105.86(15)	105.9(4)	105.81(15)
C(3)―C(3A)―C(4)	131.53(15)	131.9(4)	132.13(14)
C(3)―C(3A)―C(9B)	106.46(16)	106.5(4)	106.24(15)
O(4)―C(4)―O(5)	116.68(17)	117.0(4)	115.98(18)
O(5)―C(4)―C(3A)	114.98(14)	114.5(4)	114.44(14)
X(8)―C(8)―C(7)	119.13(15)	119.0(4)	119.30(18)
N(1)―C(9B)―C(3A)	105.87(15)	105.9(3)	106.10(15)

Table 4

Geometric parameters associated with D―H···A (A = O, π) interactions for compounds 2a–d.

Comp.	D―H···Aa (symmetry code)	H···A/Å	D···A/Å	D―H···A/º
2ab	C6―H6···Cg(4) (x, y, 1 + z)	2.89	3.820(3)	178
	C9―H9···Cg(4) (x, y, z)	2.99	3.825(3)	150(2)
	C16―H16A···Cg(3) (−x, −½ + y, −z)	2.75(3)	3.6659(18)	157
2b	C13―H13···O4 (x, y, z − 1)	2.400	3.265(7)	155
	C15―H15···O5 (2 − x, 1 − y,1 − z)	2.570	3.443(6)	157
	C7―H7···Cg(4) (x, y − 1, z)	2.57	3.460(2)	161
	C16―H16C···Cg(3) (1 − x, 1 − y, −z)	2.78	3.535(2)	136
2c	C13―H13···O4 (x, y, z + 1)	2.450	3.340(7)	161
	C15―H15···O5 (−x, 1 − y, −z)	2.580	3.450(6)	156
	C7―H7···Cg(4) (x, 1 + y, z)	2.72	3.631(5)	167
	C16―H16B···Cg(3) (1 − x, 1 − y, −z)	2.87	3.633(5)	137
2d	C13―H13···O4 (x, y, z + 1)	2.53	3.464(3)	179
	C7―H7···Cg(4) (1 + x, y, z)	2.78	3.6999(3)	171
	C9―H9···Cg(4)	2.79	3.632(3)	152

a Cg(3) the centroid of the benzenoid ring (C5AC9AC9C8C7C6C5A) and Cg(4) the centroid of the phenyl ring (C10―C15); b From reference 32.

The molecular structures of the three isomers are very similar and the major differences among them arise from the nature of the 8-substituent, Figure 1. A brief n class="Chemical">comparison with the starting coumarins points out the lengthening of C9a―C9b bond length to 1.439(5) Å (mean value of 2b-d), from a mean reported value of 1.35 Å (C3―C4 in the former coumarins) [28], in agreement with a delocalized electronic character of the pyrazole ring.

Figure 1

The molecular structures of 2b-d, from left to right, showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.

Because of the arrangement of the aromatic rings, the supramolecular architecture is almost n class="Chemical">controlled by C―H···A (A = O, π) and face to face π-stacking interactions, whose geometrical parameters are listed in Table 4. In the solid state C9―H9···Cg(4) and C9···Cg(4) distances, and C9―H9···Cg(4) angle, suggest an intramolecular C―H···π interaction S(6) in 2d, Figure 2. Even when these geometric parameters are similar among 2a-d, only those corresponding to 2d lie are in the proper range to be considered as such [29].

Figure 2

Supramolecular structure of compound 2d in the ac plane. S(6) intramolecular ring and C(8) chain forming bifacial C―H···π interactions, C(12) chain and R ring motifs are also observed.

The first dimension (1-D) is directed by C13—H13···O4C4 interactions, between an aromatic hydrogen and the n class="Chemical">oxygen of the lactone group, developing C(10) chains along the direction of the c axis in 2b-d. Molecules of 2b,c self assemble in the bc plane and 2d in the ac plane through C7―H7···Cg(4) interactions forming C(8) chains. The 2-D assembly is thus described as a R ring, in agreement with the graph set notation conventions [30], Figure 2. 2-D assembled monolayers of 2b,c and 2d are face-to-face π-stacked developing the 3-D along the a and the b axis, respectively. A C(12) chain motif complements the 3-D in compounds 2b,c through the participation of C15―H15···O5 and C16―H16B···Cg(3) contacts running along the direction of the a axis (Figure 3).

Figure 3

Intermolecular interactions for molecule 2c in the ac plane. C(12) chain motif is observed through the participation of C15―H15···O5 and C16―H16B···Cg(3) contacts running along the direction of the a axis.

Intermolecular interactions for molecule 2c in the ac plane. C(12) chain motif is observed through the participation of C15―H15···O5 and C16―H16B···n class="Chemical">Cg(3) contacts running along the direction of the a axis.

The participation of the N-phenyl ring [n class="Chemical">Cg(4)] in π-stacking is restricted to C―H···π interactions because of its disposition out of the plane. In contrast, the remaining pyrazole [Cg(1)], pyrone [Cg(2)] and benzenoid [Cg(3)] rings are lying in the same plane and thus are appropriately positioned for π-stacking. The geometric parameters associated with π-stacking interactions are listed in Table 5. Pyrazole ring is stacked with pyrone ring in compound 2a [Cg(1)···Cg(2)] [31], it further appears stacked with the Cl- or Br- substituted benzenoid ring [Cg(1)···Cg(3)] in compounds 2b and 2c. In both compounds, the π-stacking between pyrone and benzenoid rings, typical of coumarins, is also observed [Cg(2)···Cg(3)]. However, in the case of compound 2d only Cg(1) and Cg(3) are stacked, the EW group 8-NO2 diminishes the charge transfer capability of the benzenoid ring, enabling the formation of π-stacked centrosymmetric pairs with pirazole ring, the best charge transfer donor ring. In the other hand, the donor-acceptor capabilities of the benzenoid ring changes on going from 2a to 2d, according with the increase of the EW nature of the 8-substituent. Thus, the observed π-stacking trend between the rings is given by the overlapping between the best donor and acceptor ring in each molecule. This trend is consistent with those observed for other CCDC deposited structures [32], whose molecular and supramolecular analysis is missing (LOLZER, LOLZOB, LOLZUH, LOMBAQ, LOMBEU). Compounds 2a-2d are functional isomers but only 2b and 2c are isomorphous, however the supramolecular structure of all of them is almost the same, varying only in the π-stacked rings and the propagating directions of the supramolecular motifs.

Table 5

Geometric parameters associated with π···π stacking interactions for compounds 2a–2d.

Comp.	Centroidsa (symmetry code)	Intercentroid distance/A°	Dihedral angle/º	Interplanar distance/A°
2ab	Cg(1)···Cg(2) (−x, −½ + y, −z)	3.8508(9)	0.000	3.4916(1)
2b	Cg(1) · Cg(2) (1 − x, 1 − y, 1 − z)	3.6117(10)	0.30(8)	3.3563(7)
	Cg(1)···Cg(3) (2 − x, 1 − y, 1 − z)	3.6664(11)	1.33(9)	3.3697(7)
	Cg(2)···Cg(3) (2 − x, 1 − y, 1 − z)	3.6345(11)	1.23(8)	3.4103(6)
2c	Cg(1)···Cg(2) (1 − x, 1 − y, 1 − z)	3.708(2)	0.3(2)	3.4328(17)
	Cg(1)···Cg(3) (−x, 1 − y, −z)	3.727(2)	1.0(2)	3.4367(17)
	Cg(2)···Cg(3) (−x, 1 − y, −z)	3.6345(11)	1.23(8)	3.4103(6)
2d	Cg(1)···Cg(3) (1 − x, −½ + y, −z)	3.8523(8)	0.02(8)	3.5032(7)

a Cg(1) is the centroid of the pyrazole ring (N1N2C3C3AC9B), Cg(2) the centroid of the pyrone ring (O5C4C3AC9BC9AC5A), Cg(3) the centroid of the benzenoid ring (C5AC9AC9C8C7C6C5A) and Cg(4) the centroid of the phenyl ring (C10-C15); b From reference 32 (LOLZUH).

It is noteworthy that in these compounds, neither –Cl, –n class="Chemical">Br or –NO2 substituents in the benzenoid ring nor the lactone carbonyl, are involved in dipole-dipole interactions [33,34]. This observation contrasts with most of the coumarins studied by our group, whose supramolecular architectures are strongly influenced by the participation of these groups in multicentered interactions [35,36].

3. Experimental

3.1. Materials and Methods

All chemicals and solvents were of reagent grade and used as received. The starting coumarins were synthesized as reported elsewhere [33]. Melting points were measured on an Electrothermal IA 9100 apparatus and were unn class="Chemical">corrected. IR spectra were recorded neat using a Varian 3100 FT-IR EXCALIBUR series spectrophotometer. 1H- and 13C-NMR spectra were recorded on a Varian Mercury 300 (1H, 300.08; 13C, 75.46 MHz) instrument in CDCl3 solutions, unless otherwise is specified, chemical shifts are in ppm and coupling constants in Hz, measured with SiMe4 as internal reference. Mass spectra were obtained in a GC-MS system (Saturn 2100T) with an electron ionization mode (Hewlett-Packard 5972 series) using HP5. Elemental analyses were performed on a Perkin-Elmer 2400 elemental analyzer.

3.2. X-ray Data Collection and Structure Determination

Crystals suitable for X-ray analysis were obtained by slow crystallization from saturated DMF solutions. Single-crystal X-ray diffraction data for molecules 2b-d were n class="Chemical">collected on a Bruker Apex II area detector diffractometer at 293 K with Mo Kα radiation, λ = 0.71073 Å. A semiempirical absorption correction was applied using SADABS [37], and the program SAINT [37] was used for integration of the diffraction profiles. The structures were solved by direct methods using SHELXS97 [38] program of WinGX package [39]. The final refinement was performed by full-matrix least-squares methods on F2 with SHELXL97 program [37]. H atoms on C, N and O were positioned geometrically and treated as riding atoms, with C―H = 0.93–0.98 Å, and with Uiso(H) = 1.2Ueq(C). Mercury was used for visualization, molecular graphics and analysis of crystal structures [40], software used to prepare material for publication was PLATON [41]. Crystallographic data (excluding structure factors) for the structures in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication CCDC numbers 766071 2b, 766070 2c,766072 2d. Crystal data and details concerning data collection and structure refinement are given in Table 6.

Table 6

Crystal data and structure refinement details for 2b-d.

	2b	2c	2d
Chemical formula	C17H11N2O2Cl1	C17H11N2O2Br1	C17H11N3O4
Mw	310.7	355.19	321.2
Cell setting, Space group	Triclinic, P-1	Triclinic, P-1	Monoclinic, P 21/m
a (A°)	7.1177 (8)	7.1681(8)	9.4294(11)
b (A°)	9.2540 (10)	9.3210(11)	7.0064(8)
c (A°)	11.7266(13)	11.8449(14)	12.0294(14)
α (º)	110.450(2)	109.820(2)	90
β (º)	98.468(2)	97.016(2)	112.826(2)
γ (º)	97.748(2)	96.891(2)	90
V (Å 3)	701.14(8)	727.83(15)	732.50(7)
Z	2	2	2
Density (mg cm−3)	1.471	1.621	1.46
μ (mm−1)	0.281	2.831	0.11
Crystal form, color	Block, pale yellow	Block, colorless	Block, pale yellow
Crystal size (mm3)	0.48 × 0.22 × 0.19	0.40 × 0.20 × 0.20	0.45 × 0.33 × 0.30
No. of measured,	6092	7652	4922
independent and	3160	2853	2514
observed reflections	2840	2013	2261
Rint	0.024	0.054	0.024
θmax(°)	28.3	26	28.3
Refinement on	F2	F2	F2
R[F2 > 2σ(F2)], wR(F2),S	0.048, 0.116, 1.089	0.057, 0.116, 1.029	0.043, 0.122, 1.056
No. of reflections	3160	2853	2514
No. of parameters	200	200	218
Weighting scheme	1/[σ2(Fo2) + (0.0542P)2 + 0.2899P]	1/[σ2(Fo2) + (0.0542P)2 + 0.1266P]	1/[σ2(Fo2) + (0.0576P)2 + 0.321P]
	P = (Fo2 + 2Fc2)/3	P = (Fo2 + 2Fc2)/3	P = (Fo2 + 2Fc2)/3
Δρmax, Δρmin (eÅ−3)	0.411, −0.281	0.670, −0.322	0.194, −0.199

3.3. General Methods of Synthesis

6-Substituted-3-[1-(phenylhydrazono)-ethyl]-chromen-2-ones 1a-i. were synthesized from n class="Chemical">phenyl-hydrazine and 0.5 g of the corresponding coumarins, following standard procedures. The syntheses of compounds 2a [15,17], 2b [15], 2c, 2d [23] have been reported elsewhere, albeit with lack of some spectroscopic data, thus for completeness purposes they are included but elemental analysis was performed only to the new compounds 2e-f.

3-[1-(Phenylhydrazono)-ethyl]-chromen-2-one (1a). Obtained from n class="Chemical">3-acetyl-2H-1-benzopyran-2-one (0.5 g, 2.66 mmol) and phenylhydrazine (0.26 mL, 2.66 mmol) as an orange solid in 85% yield (0.633 g, 2.26 mmol), mp = 193–196 °C, IR νneat (cm−1): 3295 (N-H), 1695 (OC=O), 1596 (C=O), 1255, 1155 (C-O). 1H-NMR (DMSO-d6) δ: 9.43 (s, 1H, NH), 8.16 (s, 1H, H-4), 7.81 (d, 1H, H-5, 3J = 7.7), 7.57 (dd, 1H, H-7, 3J = 8.0, 7.5), 7.38 (d, 1H, H-8, 3J = 8.3, 3J = 8.3), 7.33 (t, 1H, H-6, 3J = 8.0, 7.6,4J = 2.2), 6.74–7.24 (m, 5H, Ph), 2.20 (s, 3H, CH3). 13C-NMR (DMSO-d6) δ: 160.2 (C-2), 153.6 (C-9), 146.2 (C-11), 139.8 (C-4), 139.2 (Ci), 132.2 (C-7), 129.5 (C-5), 129.5 (Cm), 127.9 (C-3), 125.2 (C-6), 120.0 (Cp), 116.4 (C-8), 119.9 (C-10), 113.7 (Co), 15.8 (Me). Anal. Calcd for C17H14N2O2; C, 73.37; H, 5.07; N, 10.12. Found: C, 73.27; H, 4.91; N, 10.12. m/z = 277.1 (M, 22%), 77 (20%).

6-Chloro-3-[1-(phenylhydrazono)-ethyl]-chromen-2-one (1b). Obtained from 3-acetyl-6-cloro-2H-1-benzopyran-2-one (0.5 g, 2.22 mmol) and phenylhydrazine (0.22 mL, 2.22 mmol) as an orange solid in 82% yield (0.578 g, 1.83 mmol), mp = 184–188 °C, IR νneat (cm−1): 3300 (N-H), 1703 (OC=O), 1598 (C=O), 1251, 1155 (C-O), 810 (C-Cl). 1H-NMR (DMSO-d6) δ: 9.49 (s, 1H, NH), 8.17 (s, 1H, H-4), 7.97 (d, 1H, H-5, 4J = 2.3), 7.57 (dd, 1H, H-7, 3J = 8.8, 4J = 2.3), 7.43 (d, 1H, H-8, 3J = 8.8), 6.75–7.25 (m, 5H, Ph), 2.20 (s, 3H, CH3). 13C-NMR (DMSO-d6) δ: 159.2 (C-2), 151.6 (C-9), 145.4 (C-11), 138.1 (Ci), 137.8 (C-4), 130.9 (C-7), 129.0 (C-6), 128.8 (Cm), 128.2 (C-3), 127.7 (C-5), 120.8 (Cp), 119.5 (C-10), 117.8 (C-8), 113.1 (Co), 15.0 (Me). m/z = 312 (M, 30%), 313 (8%), 240 (8%), 77 (28%).

6-Bromo-3-[1-(phenylhydrazono)-ethyl]-chromen-2-one (1c). Obtained from 3-acetyl-6n class="Chemical">-bromo-2H-1-benzopyran-2-one (0.5 g, 1.87 mmol) and phenylhydrazine (0.18 mL, 1.87 mmol) as an orange solid in 67% yield, (0.451 g, 1.25 mmol), mp = 184–186 °C, IR νneat (cm−1): 3301 (N-H), 1704 (OC=O), 1597 (C=O), 1250, 1158 (C-O), 681 (C-Br). 1H-NMR (DMSO-d6) δ: 9.48 (s, 1H, NH), 8.15 (s, 1H, H-4), 8.08 (d, 1H, H-5, 4J = 2.3), 7.68 (dd, 1H, H-7, 3J = 8.8, 4J = 2.3), 7.35 (d, 1H, H-8,3J = 8.8), 6.75–7.23 (m, 5H, Ph), 2.17 (s, 3H, CH3). 13C-NMR (DMSO-d6) δ: 159.1 (C-2), 152.0 (C-9), 145.4 (C-11), 138.1 (Ci), 137.7 (C-4), 133.8 (C-7), 130.8 (C-5), 128.9 (Cm), 128.3 (C-3), 121.3 (C-6), 119.5 (Cp), 118.1 (C-8), 116.1 (C-10), 113.1 (Co), 15.0 (Me). m/z = 356 (M, 100%), 358 (30%), 357 (20%), 278 (5%), 77 (27%).

6-Nitro-3-[1-(phenylhydrazono)-ethyl]-chromen-2-one (1d). Obtained from 3-acetyl-6-nitro-n class="Chemical">2H-1-benzopyran-2-one (0.5 g, 2.14 mmol) and phenylhydrazine (0.21 mL, 2.14 mmol) as an orange solid in 53% yield (0.370 g, 1.14 mmol), mp = 204–206 °C, IR νneat (cm−1): 3328 (N-H), 1726 (OC=O), 1604 (C=O), 1516, 1340 (C-NO2), 1239, 1113 (C-O). 1H-NMR (DMSO-d6) δ: 9.55 (s, 1H, NH), 8.84 (d, 1H, H-5, 4J = 2.6), 8.35 (dd, 1H, H-7, 3J = 9.1, 4J = 2.6), 8.40 (s, 1H, H-4), 7.60 (d, 1H, H-8, 3J = 9.1), 6.76-7.78 (5H, -Ph), 2.20 (s, 3H, CH3). 13C-NMR (DMSO-d6) δ: 159.2 (C-2), 157.1 (C-9), 144.4 (C-11), 144.2 (C-6), 137.7 (C-4), 137.5 (Ci), 130.6 (C-3), 129.6 (Cm), 126.1 (C-7), 124.2 (C-5), 121.5 (Cp), 119.9 (C-10), 117.7 (C-8), 113.6 (Co), 13.7 (Me). m/z = 322 (M, 20%), 246 (5%), 77 (15%).

6-Methoxy-3-[1-(phenylhydrazono)-ethyl]-chromen-2-one (1e). Obtained from 3-acetyl-6-methoxy-2H-1-benzopyran-2-one (0.5 g, 2.29 mmol) and phenylhydrazine (0.23 mL, 2.29 mmol) as an orange solid in 72% yield (0.512 g, 1.65 mmol), mp = 147–149 °C, IR νneat (cm−1): 3303 (N-H), 1698 (OC=O), 1574 (C=O), 1243, 1134 (C-O). 1H-NMR δ: 7.98 (s, 1H, H-4), 7.63 (s, 1H, NH), 7.24 (d, 1H, H-8, 3J = 8.1), 7.05 (dd, 1H, H-7, 3J = 9.1, 4J = 2.1), 6.86–7.30 (m, 5H,-Ph), 6.97 (d, 1H, H-5,4J = 2.4), 2.28 (s, 3H, CH3). 13C-NMR δ: 160.9 (C-2), 156.3 (C-6), 148.4 (C-9), 144.8 (C-11), 139.7 (C-4), 139.3 (Ci), 129.5 (Cm), 127.9 (C-3), 120.9 (Cp), 120.1 (C-10), 119.7 (C-7), 117.6 (C-8), 110.2 (C-5), 113.5 (Co), 14.1 (Me). m/z = 307 (M, 24%), 230 (5%), 77 (15%).

8-Methoxy-3-[1-(phenylhydrazono)-ethyl]-chromen-2-one (1f). Obtained from 3-acetyl-8-methoxy-2H-1-benzopyran-2-one (0.5 g, 2.29 mmol) and phenylhydrazine (0.23 mL, 2.29 mmol) as an orange solid in 91% yield (0.647 g, 2.09 mmol), mp = 152–156 °C, IR νneat (cm−1): 3306 (N-H), 1700 (OC=O), 1601 (C=O), 1263, 1160 (C-O). 1H-NMR δ: 8.02 (s, 1H, H-4), 7.59 (s, 1H, NH), 7.28 (d, 1H, H-7, 3J = 7.7), 7.17 (t, 1H, H-6, 3J = 7.7), 7.06 (d, 1H, H-5, 3J = 7.7), 6.87-7.36 (m, 5H, Ph), 2.29 (s, 3H, CH3). 13C-NMR δ: 160.2 (C-2), 147.1 (C-8), 144.7 (C-11), 140.0 (C-4), 143.5 (C-9), 139.3 (Ci), 129.5 (Cm), 127.9 (C-3), 124.6 (C-5), 120.9 (C-6), 120.4 (C-10), 120.0 (Cp), 113.5 (Co), 113.4 (C-7), 14.1 (Me). m/z = 306.2 (M, 100%), 230 (5%), 77 (17%).

6-Bromo-8-methoxy-3-[1-(phenylhydrazono)-ethyl]-chromen-2-one (1g). Obtained from 3-acetyl-6n class="Chemical">-bromo-8-methoxy-2H-1-benzopyran-2-one (0.5 g, 1.68 mmol) and phenylhydrazine (0.16 mL, 1.68 mmol) as an orange solid in 74% (0.485 g, 1.25 mmol), mp = 185–188 °C, IR νneat (cm−1) 3312 (N-H), 1713 (OC=O), 1599 (C=N), 1258 (C-O). 1H-NMR δ: 7.95 (s, 1H, H-4), 7.58 (s, 1H, NH), 7.34 (s, 1H, H-5), 7.24 (s, 1H, H-7), 6.84–7.29 (m, 5H, Ph), 2.28 (s, 3H, CH3), 3.96 (s, 3H, OMe). 13C-NMR δ: 156.3 (C-2), 151.6 (C-8), 147.8 (C-9), 144.5 (C-11), 138.5 (C-13), 138.3 (C-4), 129.5 (Cm), 128.8 (C-3), 121.1 (Cp), 122.0 (C-5), 121.4 (C-6), 116.9 (C-10), 116.5 (C-7), 113.5 (Co), 56.7 (MeO–), 13.8 (Me). m/z = 386 (M, 100%), 308 (5%), 77 (20%).

8-Bromo-6-chloro-3-[1-(phenylhydrazono)-ethyl]-chromen-2-one (1h). Obtained from 3-acetyl-8-bromo-6-chloro-2H-1-benzopyran-2-one (0.5 g, 1.66 mmol) and phenylhydrazine (0.16 mL, 1.66 mmol) as an orange solid in 84% yield (0.548 g, 1.39 mmol), mp = 199–201 °C, IR νneat (cm−1) 3312 (N-H), 1707 (OC=O), 1530 (C=N), 1248 (C-O). 1H-NMR δ: 7.95 (s, 1H, H-4), 7.62 (s, 1H, NH), 7.71 (d, 1H, H-7, 4J = 2.4), 7.51 (d, 1H, H-5, 4J = 2.4), 6.90-7.29 (m, 5H, Ph.), 2.29 (s, 3H, CH3). 13C-NMR δ:159.2 (C-2), 144.3 (C-11), 140.2 (C-9), 137.8.5 (C-13), 137.6 (C-4), 134.2 (C-7), 130.1 (C-6), 129.6 (C-14), 129.2 (C-3), 126.9 (C-5), 121.6 (C-10), 113.5 (C-15), 110.7 (C-8), 13.8 (Me). m/z = 390.1 (M, 100%), 391.1 (30%), 392.0 (25%), 315 (5%), 76.9 (30%).

6,8-Dichloro-3-[1-(phenylhydrazono)-ethyl]-chromen-2-one (1i). Obtained from 3-acetyl-6,8-dichloro-2H-1-benzopyran-2-one (0.5 g, 1.95 mmol) and phenylhydrazine (0.19 mL, 1.95 mmol) as an orange solid in 82% yield (0.557 mg, 1.60 mmol), mp = 196–198 °C, IR νneat (cm−1) 3311 (N-H), 1709 (OC=O), 1533 (C=N), 1162 (C-O). 1H-NMR δ: 7.96 (s, 1H, H-4), 7.62 (s, 1H, NH), 7.55 (d, 1H, H-7,4J = 2.2), 7.41 (2, 1H, H-5, 4J = 2.2), 6.94–7.30 (m, 5H, Ph), 2.29 (s, 3H, CH3). 13C-NMR δ: 159.0 (C-2), 151.3 (C-9), 144.3 (C-11), 138.8 (C-13), 137.6 (C-4), 134.2 (C-6), 131.3 (C-7), 129.8 (Cm), 129.7 (C-3), 124.2 (C-8), 121.6 (C-10), 121.3 (Cp), 113.6 (Co), 13.8 (Me). m/z = 347 (M, 20%), 346.3 (55%), 274 (8%), 77 (30%).

3-Methyl-1-phenyl-1H-chromeno[4,3-c]pyrazol-4-one (2a). Cu(CH3COO)2·H2O (0.025 g, 0.125 mmol) was dissolved in ethyl alcohol (20 mL) and added to a solution of 1a (0.500 g, 1.78 mmol) and ethyl alcohol (30 mL). The mixture was refluxed during 3 h, the resulting solid was filtered, washed with cold ethyl alcohol (5 mL) and several times with distilled water, air dried and recrystallized from ethyl acetate to obtain 0.372 mg (1.34 mmol) of 2a as a white powder in 76% yield, mp = 227–230 °C, IR νneat (cm−1): 1726 (OC=O), 1272, 1202 (C-O). 1H-NMR δ: 7.44 (t, 1H, H-7, 3J = 8.6, 4J = 1.6 Hz), 7.40 (d, 1H, H-6, 3J = 8.1), 7.09 (d, 1H, H-9, 3J = 7.9), 7.02 (t, 1H, H-8, 3J = 7.9, 4J = 1.6), 7.52–7.62 (m, 5H, Ph), 2.67 (s, 3H, CH3). 13C-NMR δ: 158.3 (C-4), 153.4 (C-5a), 151.0 (C-3), 141.9 (C-9b), 139.5 (Ci), 131.3 (C-7), 130.4 (Cp), 130.1 (Co), 127.0 (Cm), 124.1 (C-8), 122.6 (C-9), 118.2 (C-6), 112.0 (C-9a), 106.5 (C-3a), 13.1 (Me). m/z = 276.2 (M, 100%), 247.3 (5%), 206.2 (14%), 77.0 (16%).

8-Chloro-3-methyl-1-phenyl-1H-chromeno[4,3-c]pyrazol-4-one (2b). Obtained as described for 2a starting from 1b (0.500 g, 1.59 mmol) to give 2b (0.343 g, 1.10 mmol, 69% yield) as a pale yellow powder, mp = 280–283 °C, IR νneat (cm−1): 1743 (OC=O), 1204 (C-O), 814 (C-Cl). 1H-NMR δ: 7.58 (dd, 1H, H-7 3J = 8.8, 4J = 1.9), 7.35 (d, 1H, H-6 3J = 8.8), 7.03 (d, 1H, H-9 4J = 1.9), 7.38–7.65 (m, 5H, Ph), 2.68 (s, 3H, CH3). 13C-NMR δ: 157.6 (C-4), 151.8 (C-5a), 151.2 (C-3), 140.7 (C-9b), 139.0 (Ci), 131.2 (C-7), 130.8 (C-p), 130.2 (C-o), 129.5 (C-8), 126.9 (C-m), 122.3 (C-9), 119.6 (C-6), 113.1 (C-9a), 106.8 (C-3a), 13.1 (Me). m/z = 310.2 (M, 100%), 311.0 (70%), 309.3 (45%), 275.3 (5%), 77 (22%).

8-Bromo-3-methyl-1-phenyl-1H-chromeno[4,3-c]pyrazol-4-one (2c). Obtained as described for 2a starting from 1c (0.500 g, 1.39 mmol) to afford 2c (0.388 g, 1.09 mmol, 78% yield) as a white powder, mp = 278–280 °C, IR νneat (cm−1): 1742 (OC=O), 1266, 1203 (C-O). 1H-NMR δ: 7.52 (dd, 1H, H-7), 7.28 (d, 1H, H-6, 3J = 8.9), 7.16 (d, 1H, H-9 4J = 2.4), 7.54–7.78 (m, 5H, Ph), 2.67 (s, 3H, CH3). 13C-NMR δ: 157.6 (C-4), 152.3 (C-5a), 151.2 (C-3), 140.6 (C-9b), 139.0 (Ci), 134.0 (C-7), 130.8 (Cp), 130.3 (Co), 126.9 (Cm), 125.3 (C-9), 119.9 (C-8), 116.8 (C-6), 113.7 (C-9a), 106.8 (C-3a), 13.1 (Me). m/z = 354.3 (M, 80%), 356.1 (100%), 356.9 (35%), 358.0 (5%), 274.3 (5%), 77 (25).

3-Methyl-8-nitro-1-phenyl-1H-chromeno[4,3-c]pyrazol-4-one (2d). Obtained as described for 2a starting from 1d (0.500 g, 1.54 mmol) to give 2d (0.412 g, 1.28 mmol, 83% yield) as a pale yellow powder, mp = 248–254 °C, IR νneat (cm−1): 1756 (OC=O), 1259, 1207 (C-O), 1519 (C-NO2). 1H-NMR δ: 8.31 (dd, 1H, H-7, 3J = 9.1, 4J = 2.6), 8.02 (d, 1H, H-9 4J = 2.6), 7.55 (d, 1H, H-6, 3J = 9.1), 7.56–7.72 (m, 5H, Ph), 2.71 (s, 3H, CH3). 13C-NMR δ: 156.9 (C-4), 156.6 (C-5a), 151.5 (C-3), 143.6 (C-9b), 140.2 (C-8), 138.6 (Ci), 131.2 (Cp), 130.6 (Co), 126.7 (Cm), 126.0 (C-7), 119.3 (C-9), 118.8 (C-6), 112.4 (C-9a), 106.8 (C-3a), 13.1 (Me). m/z = 321.0 (M, 100%), 320.2 (25%), 322.9 (5%), 275.3 (10%), 77 (21%).

8-Methoxy-3-methyl-1-phenyl-1H-chromeno[4,3-c]pyrazol-4-one (2e). Obtained as described for 2a starting from 1e (0.500 g, 1.61 mmol) to obtain 2e (0.258 g, 0.84 mmol, 52% yield) as a white powder, mp = 232–234 °C, IR νneat (cm−1): 1734 (OC=O), 1238, 1203 (C-O). 1H-NMR δ: 7.32 (d, 1H, H-6,3J = 9.0), 6.98 (dd, 1H, H-7, 3J = 9.0, 4J = 3.1), 6.50 (d, 1H, H-9, 4J = 3.1), 7.63-7.54 (m, 5H, Ph), 2.68 (s, 3H, CH3). 13C-NMR δ: 158.4 (C-4), 155.6 (C-8), 151.0 (C-3), 147.9 (C-5a), 141.9 (C-9b), 139.5 (Ci), 130.5 (Co), 130.5 (Cp), 127.4 (Cm), 119.2 (C-7), 118.8 (C-6), 112.1 (C-9a), 106.7 (C-3a), 105.5 (C-9), 13.4 (Me). m/z = 306.1 (M, 100%), 291.3 (28%), 277 (3%), 77 (22%). Anal. Calcd. for C18H14N2O3; C, 70.58; H, 4.61; N, 9.14. Found: C, 70.22; H, 4.50; N, 9.00.

6-Methoxy-3-methyl-1-phenyl-1H-chromeno[4,3-c]pyrazol-4-one (2f). Obtained as described for 2a starting from 1f (0.500 g, 1.61 mmol) to give 2f (0.248 g, 0.806 mmol, 50% yield) as a white powder, mp = 238–240 °C, IR νneat (cm−1): 1743 (OC=O), 1273, 1207 (C-O). 1H-NMR δ: 7.02 (dd, 1H, H-7,3J = 8.2, 7.6), 6.97 (t, 1H, H-8, 3J = 7.6, 8.2), 6.65 (dd, 1H, H-9 3J = 7.6, 4J = 1.5), 7.54–7.62 (m, 5H, Ph), 2.69 (s, 3H, CH3). 13C-NMR δ: 157.6 (C-4), 151.0 (C-3), 148.4 (C-6), 143.3 (C-5a), 142.1 (C-9b), 139.6 (Ci), 130.4 (Cp), 130.0 (Co), 127.2 (Cm), 123.9 (C-8), 114.1 (C-9), 112.9 (C-7), 112.7 (C-9a), 106.6 (C-3a), 13.2 (Me). m/z = 306.1 (M, 100%), 291.3 (5%), 277 (20%), 77 (22%). Anal. Calcd. for C18H14N2O3; C, 70.58; H, 4.61; N, 9.14. Found: C, 70.83; H, 4.70; N, 9.00.

8-Bromo-3-methyl-6-methoxy-1H-chromeno[4,3-c]pyrazol-4-one (2g). Obtained as described for 2a starting from 1g (0.500 g, 1.28 mmol) to obtain 2g (0.393 g, 1.01 mmol, 79% yield) as a pale yellow powder, mp = 289–292 °C, IR νneat (cm−1): 1744 (OC=O), 1275, 1205 (C-O). 1H-NMR δ: 6.72 (s, 1H, H-9), 7.06 (s, 1H, H-6), 7.51-7.62 (m, 5H, Ph), 2.67 (s, 3H, CH3). 13C-NMR δ: 156.7 (C-4), 151.1 (C-5a), 148.9 (C-3), 142.3 (C-6), 140.1 (C-9b), 139.0 (C-10), 130.7 (C-9), 130.1 (C-11), 127.0 (C-12), 123.9 (C-5), 123.3 (C-8), 116.5 (C-13), 116.1 (C-7), 113.7 (C-9a), 106.8 (C-3a), 13.1 (Me). m/z = 384.5 (M, 80%), 386.2 (100%), 385.5 (25%), 357.5 (10%), 290.5 (10%), 77.0 (25%). Anal. Calcd. for C18H13N2O3Br; C, 56.13; H, 3.40; N, 7.27. Found: C, 55.88; H, 3.40; N, 7.20.

6-Bromo-8-Chloro-3-methyl-1H-chromeno[4,3-c]pyrazol-4-one (n class="Chemical">2h). Obtained as described for 2a starting from 1h (0.5 g, 1.27 mmol) to obtain 2h (0.249 g, 0.64 mmol, 50% yield) as a pale yellow powder, mp = 259–261 °C, IR νneat (cm−1): 1749 (OC=O), 1277, 1224 (C-O). 1H-NMR δ: 6.90 (s, 1H, H-9), 7.82 (s, 1H, H-7), 7.53-7.65 (m, 5H, Ph), 2.65 (s, 3H, CH3). 13C-NMR δ: 156.2 (C-4), 151.1 (C-5a), 148.2 (C-3), 140.2 (C-9b), 138.8 (C-10), 134.2 (C-7), 130.9 (C-9), 130.6 (C-11), 129.5 (C-8), 126.9 (C-12), 121.4 (C-13), 113.9 (C-6), 112.6 (C-9a), 106.8 (C-3a), 13.0 (Me). m/z = 390.0 (M, 100%), 389.5 (60%), 388.5 (62%), 310 (5%), 77(25%). Anal. Calcd. for C17H10N2O2BrCl; C, 52.40; H, 2.59; N, 7.19. Found: C, 52.70; H, 2.63; N, 7.00.

6,8-Dichloro-3-methyl-1H-chromeno[4,3-c]pyrazol-4-one (2i). Obtained as described for 2a starting from 1i (0.5 g, 1.43 mmol) to obtain 2i (0.259 g, 0.74 mmol, 52% yield) as a pale yellow powder, mp = 224–226 °C, IR νneat (cm−1): 1750 (OC=O), 1225 (C-O). 1H-NMR δ: 6.90 (s, 1H, H-9), 7.47 (s, 1H, H-7), 7.52-7.64 (m, 5H, Ph), 2.65 (s, 3H, CH3). 13C-NMR δ: 156.2 (C-4), 151.1 (C-5a), 147.8 (C-3), 140.2 (C-9b), 138.8 (C-10), 131.3 (C-7), 130.9 (C-9), 130.3 (C-11), 129.1 (C-8), 126.9 (C-12), 124.1 (C-6), 120.8 (C-13), 114.0 (C-9a), 106.8 (C-3a), 13.0 (Me). m/z = 344.5 (M, 100%), 346.2 (80%), 345.3 (68%), 308.5, 77 (22%). Anal. Calcd. for C17H10N2O2Cl2; C, 59.15; H, 2.92; N, 8.11. Found: C, 58.90; H, 2.89; N, 8.00.

4. Conclusions

3-Methyl-1-phenyl-1H-chromeno[4,3-c]pyrazol-4-one (2a) spontaneously crystallizes from CHCl3solutions of 3-[1-(phenyl-hydrazono)-ethyl]-chromen-2-one (1a) whereas the 6-substituted isomers 1b-i failed to do so, requiring Cu(n class="CellLine">CH3COO)2·H2O as catalyst to yield the corresponding 1-phenyl-chromeno[4,3-c]pyrazol-4-ones 2b-i in moderate to good yields (50–83%) under mild conditions. The NMR data in solution and the X-ray data in the solid state are consistent with the N-phenyl ring almost perpendicular to the three fused rings chromeno-pyrazole system. In the solid state this geometrical arrangement of the aromatic rings determines the supramolecular architecture by C―H···A (A = O, π) and face to face π-stacking interactions which are very similar among 2b-d, varying only in the nature of the π-stacked rings and in the propagating direction. The observed π-stacking trend between chromeno and pyrazole rings is given by the overlapping between the best donor and acceptor rings in each molecule, modulated by the electronic character of the X and Y substituents.