2′-Methyl-3,5-diphenyl­spiro­[4,6-dioxa-2-aza­bicyclo­[3.2.0]hept-2-ene-7,4′-iso­quinoline]-1′,3′(2′H,4′H)-dione

Hoong-Kun Fun; Jia Hao Goh; Haitao Yu; Yan Zhang

doi:10.1107/S1600536810008718

. 2010 Mar 13;66(Pt 4):o803–o804. doi: 10.1107/S1600536810008718

2′-Methyl-3,5-diphenylspiro[4,6-dioxa-2-azabicyclo[3.2.0]hept-2-ene-7,4′-isoquinoline]-1′,3′(2′H,4′H)-dione

Hoong-Kun Fun ^a,^*,^‡, Jia Hao Goh ^a,^§, Haitao Yu ^b, Yan Zhang ^b

PMCID: PMC2984019 PMID: 21580639

Abstract

In the title compound, C₂₅H₁₈N₂O₄, the tetrahydropyridine ring adopts a distorted envelope conformation with the spiro C atom at the flap position [deviation = 0.470 (2) Å]. The dihydro–oxazole ring is planar (r.m.s. deviation = 0.013 Å) and it makes dihedral angles of 73.43 (8) and 4.24 (8)° with the two attached phenyl rings. The dihedral angle between oxetane and oxazole planes is 67.44 (9)°. In the crystal structure, C—H⋯O hydrogen bonds link neighbouring molecules into zigzag chains along the b axis and these chains are linked via C—H⋯π interactions.

Related literature

For general background to and applications of isoquinolinedione derivatives, see: Hall et al. (1994 ▶); Malamas & Hohman (1994 ▶); Nan et al. (2004 ▶). For ring conformations, see: Cremer & Pople (1975 ▶). For related structures, see: Fun et al. (2010 ▶); Wang et al. (2000 ▶). For bond-length data, see: Allen et al. (1987 ▶). For the stability of the temperature controller used for the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₂₅H₁₈N₂O₄
M _r = 410.41
Monoclinic,
a = 13.3142 (3) Å
b = 8.0366 (2) Å
c = 19.1913 (5) Å
β = 109.882 (1)°
V = 1931.09 (8) Å³
Z = 4
Cu Kα radiation
μ = 0.79 mm⁻¹
T = 100 K
0.27 × 0.26 × 0.25 mm

Data collection

Bruker SMART APEX DUO CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.815, T _max = 0.830
32042 measured reflections
3254 independent reflections
3227 reflections with I > 2σ(I)
R _int = 0.018

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.150
S = 1.35
3254 reflections
353 parameters
All H-atom parameters refined
Δρ_max = 0.80 e Å⁻³
Δρ_min = −0.88 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810008718/ci5051sup1.cif

e-66-0o803-sup1.cif^{(24.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810008718/ci5051Isup2.hkl

e-66-0o803-Isup2.hkl^{(159.7KB, hkl)}

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

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

Cg1 is the centroid of the C13–C18 benzene ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C17—H17A⋯O1ⁱ	0.97 (2)	2.51 (2)	3.213 (2)	129 (1)
C23—H23A⋯Cg1ⁱⁱ	0.96 (2)	2.66 (2)	3.5904 (18)	166 (2)

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

Acknowledgments

HKF and JHG thank Universiti Sains Malaysia (USM) for the Research University Golden Goose grant (No. 1001/PFIZIK/811012). Financial support from the Ministry of Science and Technology of China of the Austria–China Cooperation project (grant No. 2007DFA41590) is acknowledged. JHG also thanks USM for the award of a USM fellowship.

supplementary crystallographic information

Comment

1,3,4(2H)-Isoquinolinetrione derivatives have a variety of biological activities and are synthetic precursors for many naturally occuring alkaloids. On the other hand, the N-analogues of homophthalic anhydride, 1,3-isoquinolinedione and its derivatives, have a wide range of biological activities and their structural modifications with the aim of finding new drugs and medicine have drawn increasing research interests (Malamas & Hohman, 1994; Hall et al., 1994). Some substituted 1,3,4(2H)-isoquinolinetrione and their derivatives have been reported to treat neurodegenerative diseases, especially as the medicine for Alzhermer's disease, apoplexy and brain ischernic injuries (Nan et al., 2004). The crystal structure of Z-2-methyl-3'-phenyl-spiro[isoquinoline-4,2'-oxirane]-1,3-dione has been reported (Wang et al., 2000). In view of the importance of the title compound as a caspase inhibitor, this paper reports its crystal structure.

In the title isoquinoline-1,3-dione derivative (Fig. 1), the dihydro-oxazole ring (C10/C11/O4/C12/N2) is essentially planar, with a maximum deviation of 0.019 (1) Å at atom O4. The oxazole ring makes dihedral angles of 73.43 (8) and 4.24 (8)°, respectively, with C13–C18 and C19–C24 benzene rings attached to it. The tetrahydropyridine ring of the tetrahydroisoquinoline ring system adopts a distorted envelope conformation with spiro carbon C9 as the flap; the puckering amplitude Q = 0.352 (2) Å; θ = 108.2 (3)° and φ = 287.0 (3)° (Cremer & Pople, 1975). The oxetane plane (C9-C11/O3) is inclined at a dihedral angle of 67.44 (9)° with the oxazole ring. Bond lengths (Allen et al., 1987) and angles are normal and comparable to those observed in related isoquinoline-1,3-dione structures (Fun et al., 2010; Wang et al., 2000).

In the crystal structure (Fig. 2), intermolecular C17—H17A···O1 hydrogen bonds (Table 1) link the molecules into zigzag chains along the b axis. The adjacent chains are cross-linked by intermolecular C—H···π interactions (Table 1) involving the C13-C18 benzene ring (centroid Cg1).

Experimental

The title compound was obtained from the reaction between 1,3,4(2H)-isoquinolinetrione (189 mg, 1 mmol) and 2,5-diphenyloxazole (440 mg, 2 mmol). The compound was purified by flash column chromatography in ethyl acetate and petroleum ether. X-ray quality single crystals of the title compound were obtained by slow evaporation of a chloroform solution.