Methyl 4′-benzyl-2,2′-dimethyl-1,3-dioxo-2,3-dihydro-1H,4′H-spiro­[iso­quinoline-4,5′-oxazole]-4′-carboxyl­ate

Hoong-Kun Fun; Ching Kheng Quah; Chengmei Huang; Haitao Yu

doi:10.1107/S160053681101899X

. 2011 May 25;67(Pt 6):o1517–o1518. doi: 10.1107/S160053681101899X

Methyl 4′-benzyl-2,2′-dimethyl-1,3-dioxo-2,3-dihydro-1H,4′H-spiro[isoquinoline-4,5′-oxazole]-4′-carboxylate

Hoong-Kun Fun ^a,^*,^‡, Ching Kheng Quah ^a,^§, Chengmei Huang ^b, Haitao Yu ^b

PMCID: PMC3120312 PMID: 21754882

Abstract

In the isoquinoline ring system of the title molecule, C₂₂H₂₀N₂O₅, the N-heterocyclic ring is in a half-boat conformation. The least-squares plane of the dioxa-2-azaspiro ring [maximum deviation = 0.076 (1) Å] and forms a dihedral angle of 14.54 (4)° with the phenyl ring. In the crystal, molecules are linked via intermolecular C—H⋯O hydrogen bonds into layers parallel to (100).

Related literature

For general background to and the potential biological activity of the title compound, see: Du et al. (2008 ▶); Chen et al. (2006 ▶); Mitchell et al. (1995 ▶, 2000 ▶); Galliford & Scheidt (2007 ▶); Badillo et al. (2010 ▶); Wang et al. (2010 ▶); Nair et al. (2002 ▶); Huang et al. (2011 ▶). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 ▶). For standard bond-length data, see: Allen et al. (1987 ▶). For ring conformations, see: Cremer & Pople (1975 ▶). For related structures, see: Fun et al. (2011a ▶,b ▶,c ▶,d ▶).

Experimental

Crystal data

C₂₂H₂₀N₂O₅
M _r = 392.40
Triclinic,
a = 8.6834 (7) Å
b = 11.1683 (9) Å
c = 11.3085 (9) Å
α = 100.638 (2)°
β = 106.347 (2)°
γ = 109.383 (2)°
V = 944.72 (13) Å³
Z = 2
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 100 K
0.57 × 0.32 × 0.24 mm

Data collection

Bruker SMART APEXII DUO CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.937, T _max = 0.977
32434 measured reflections
8179 independent reflections
7354 reflections with I > 2σ(I)
R _int = 0.021

Refinement

R[F ² > 2σ(F ²)] = 0.037
wR(F ²) = 0.109
S = 1.04
8179 reflections
265 parameters
H-atom parameters constrained
Δρ_max = 0.52 e Å⁻³
Δρ_min = −0.28 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/S160053681101899X/rz2598sup1.cif

e-67-o1517-sup1.cif^{(22.6KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053681101899X/rz2598Isup2.hkl

e-67-o1517-Isup2.hkl^{(400.1KB, hkl)}

Supplementary material file. DOI: 10.1107/S160053681101899X/rz2598Isup3.cml

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

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C15—H15A⋯O5ⁱ	0.93	2.50	3.4311 (11)	179
C19—H19B⋯O5ⁱⁱ	0.96	2.43	3.2594 (11)	145
C22—H22A⋯O3ⁱⁱⁱ	0.96	2.53	3.2479 (8)	132

Open in a new tab

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

Acknowledgments

HKF and CKQ thank Universiti Sains Malaysia for the Research University Grant (No. 1001/PFIZIK/811160). Financial support from the Program for New Century Excellent Talents in University (NCET-08-0271) of China is also acknowledged.

supplementary crystallographic information

Comment

Isoquinoline-1,3,4-trione derivatives were reported to be a kind of small molecular inhibitor against caspase-3 which can promote apoptosis of the cells (Du et al., 2008; Chen et al., 2006). They can also attenuate apoptosis of neuronal cells induced by β-amyloid and have been reported to be redox mediators of photosystems I (Mitchell et al., 2000; 1995). Spirocyclic oxindoles have emerged as attractive synthetic targets because of their prevalence in numerous natural products and their important biological activity (Galliford & Scheidt, 2007). Among them, the synthesis of spirooxindole oxazoles is of greatest interest (Badillo et al., 2011; Wang et al.; 2010; Nair et al., 2002). As a kind of analog of spiroindole oxazolines, spiroisoquinolineoxazolines have rarely been researched. Since a lot of bioactive natural products contain isoquinoline or oxazole rings, it is necessary to develop a methodology to construct such moieties. The title compound, which was derived from isoquinoline-1,3,4-trione and oxazoles (Huang et al., 2011), may has a potential use in biochemical and pharmaceutical fields. Due to the importance of the isoquinoline-1,3,4-trione derivatives, we report in this paper the crystal structure of the title compound.

In the title racemic compound, Fig. 1, the isoquinoline ring system (N1/C1-C9) is not completely planar, the N-heterocyclic ring (N1/C1-C3/C8/C9) being distorted towards a half-boat conformation with atom C9 deviating by 0.216 (1) Å from the mean plane through the remaining atoms, puckering parameters (Cremer & Pople, 1975) Q = 0.3259 (7) Å, Θ = 112.68 (12)° and φ = 284.58 (13)°. The dioxa-2-azaspiro ring (N2/O3/C9/C10/C18) [maximum deviation of 0.076 (1) Å for atom C9] is inclined at a dihedral angle of 14.54 (4)° with the phenyl ring (C12-C17). Bond lengths (Allen et al., 1987) and angles are within normal ranges and comparable to those found in related structures (Fun et al., 2011a,b,c, d).

In the crystal structure (Fig. 2), molecules are linked via intermolecular C15–H15A···O5, C19–H19B···O5 and C22–H22A···O3 hydrogen bonds (Table 1) into two-dimensional layers parallel to (100).

Experimental

The title compound was the main product from the acid-catalyzed transformation of the photocycloadduct of isoquinoline-1,3,4-trione and 4-benzyl-5-methoxy-2-methyloxazole. The compound was purified by flash column chromatography with ethyl acetate/petroleum ether (1:4 v/v) as eluents. X-ray quality crystals of the title compound were obtained from slow evaporation of an acetone and petroleum ether solution (1:5 v/v). M.p. 451-453 K.