Benzyl 5-phenyl­pyrazolo­[5,1-a]isoquino­line-1-carboxyl­ate

Yu-Kun Lu; Xiao Yao; Li-Wen Luo; Ren-Qing Lü; Yun-Qi Liu

doi:10.1107/S1600536811050586

. 2011 Nov 30;67(Pt 12):o3488. doi: 10.1107/S1600536811050586

Benzyl 5-phenylpyrazolo[5,1-a]isoquinoline-1-carboxylate

Yu-Kun Lu ^a,^*, Xiao Yao ^b, Li-Wen Luo ^a, Ren-Qing Lü ^a, Yun-Qi Liu ^b

PMCID: PMC3239112 PMID: 22199960

Abstract

In the title compound, C₂₅H₁₈N₂O₂, the pyrazolo[5,1-a]isoquinoline ring system is approximately planar [maximum deviation = 0.027 (2) Å] and is oriented at dihedral angles of 57.22 (6) and 71.36 (7)° with respect to the two phenyl rings. The phenyl rings are twisted to each other by a dihedral angle of 66.33 (8)°. A weak intramolecular C—H⋯O hydrogen bond occurs. In the crystal, weak C—H⋯π interactions are present.

Related literature

For the biological activity of fused isoquinoline compounds, see: Aubry et al. (2004 ▶); Marco et al. (2005 ▶); Reddy et al. (1999 ▶). For related structures, see: Chen & Wu (2010 ▶); Ye et al. (2010 ▶); Yu et al. (2011a ▶,b ▶). For selected examples of multi-component reactions, see: Dömling & Ugi (2000 ▶); Nair et al. (2003 ▶); Ramon & Yus (2005 ▶).

Experimental

Crystal data

C₂₅H₁₈N₂O₂
M _r = 378.41
Monoclinic,
a = 9.161 (3) Å
b = 18.397 (6) Å
c = 11.621 (4) Å
β = 98.132 (6)°
V = 1938.9 (12) Å³
Z = 4
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 173 K
0.22 × 0.15 × 0.11 mm

Data collection

Rigaku R-AXIS RAPID diffractometer
9583 measured reflections
3378 independent reflections
1852 reflections with I > 2σ(I)
R _int = 0.098

Refinement

R[F ² > 2σ(F ²)] = 0.050
wR(F ²) = 0.116
S = 0.87
3378 reflections
263 parameters
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.24 e Å⁻³

Data collection: PROCESS-AUTO (Rigaku, 1998 ▶); cell refinement: PROCESS-AUTO; data reduction: PROCESS-AUTO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg, 1999 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, New_Global_Publ_Block. DOI: 10.1107/S1600536811050586/xu5395sup1.cif

e-67-o3488-sup1.cif^{(27.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811050586/xu5395Isup2.hkl

e-67-o3488-Isup2.hkl^{(165.7KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

Cg1 and Cg2 are the centroids of the N1/N2C11/C16/C17 and C20–C25 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C15—H15A⋯O1	0.95	2.17	3.012 (3)	148
C1—H1A⋯Cg1ⁱ	0.95	2.76	3.484 (3)	134
C14—H14A⋯Cg2ⁱⁱ	0.95	2.68	3.594 (3)	161

Open in a new tab

Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

This work was supported by the Natural Science Foundation of Shandong Province, China (ZR2011BQ004) and the Fundamental Research Funds for the Central Universities in China (09CX04045A).

supplementary crystallographic information

Comment

In the last decade, diversity-oriented synthesis has been widely used to efficiently generate diverse small molecules. Among the strategies employed in diversity-oriented chemical synthesis, multi-component reactions are very attractive processes that push the limits of synthetic efficiency by using more than two reactants to create novel products with an optimal number of new bonds and functionalities (Dömling & Ugi, 2000; Nair et al., 2003; Ramon & Yus, 2005). Among the family of isoquinolines, the fused isoquinolines have attracted much attention owing to their biological activities including potent inhibitor of human topoisomerase I and selective inhibition against HIV-1 integrase in vitro (Aubry et al., 2004; Marco et al., 2005; Reddy et al., 1999). We report herein on the single-crystal X-ray diffraction study of the title compound, synthesized from 2-(phenylethynyl)benzaldehyde, sulfonohydrazide and benzyl acrylate in DCE/DMAc.

The molecular structure of the title compound is shown in Fig. 1, the bond lengths and angles are normal and correspond to those observed in related structures (Chen & Wu, 2010; Ye et al., 2010; Yu et al., 2011a; Yu et al., 2011b). It is compound of three aromatic rings namely, a pyrazolo[5,1-a]isoquinoline ring [A = (N1, N2, C7—C17)], two benzene ring [B = (C1—C6)] and [C = (C20—C25], with the dihedral angles of 57.22 (6)°, 71.36 (6)° and 66.33 (8)° between the mean planes A/B, A/C and B/C, respectively; and the carboxyl group is twisted at an angle of 8.78 (9)° relative to the A skeleton. Atoms C16 in A ring and C20 in the benzene ring are joined by the ester group (C18/O1/O2/C19) giving the torsion angles C18—O2—C19—C20 and C19—O2—C18—C16 are -96.2 (2)° and -179.81 (17)°, respectively. Atom N1 has a trigonal configuration, the sum of three bond angles around it being 360°. The mean planes of the adjacent A moieties are parallel [at an angle 0.00 (5)°] or inclined at an angle of 37.69 (4)° in the crystal lattice.

In the crystal structure, molecules are connected via C—H···π interactions (Fig. 2 and Table 1), forming a three-dimensional supramolecular framework (Fig. 3), where Cg1 and Cg2 are the centroids of C11, C16, C17, N1, N2 and C20–C25 rings, respectively.

Experimental

The reaction was performed in test tube under nitrogen atmosphere. 2-(phenylethynyl)benzaldehyde (0.2 mmol) was added to a solution of sulfonohydrazide (0.2 mmol) in DCE (0.5 ml). The mixture was stirred at room temperature for 30 min. Then AgOTf (7.7 mg, 0.01 mmol) was added and the reaction mixture was heated to 70 ^oC for 1 h. Subsequently, benzyl acrylate (0.4 mmol) and DMAc (2 ml) were added in the mixture. After completion of reaction as indicated by TLC, the reaction was quenched with aqueous NH₄Cl (10 ml, 1.0 M), extracted with EtOAc (10 ml), dried by anhydrous Na₂SO₄. Evaporation of the solvent followed by purification on silica gel provided the crystals suitable for X-ray analysis.