Methyl 2,2′-dimethyl-4′-[2-(methyl­sulfan­yl)eth­yl]-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/S1600536811030133

. 2011 Aug 2;67(Pt 9):o2216–o2217. doi: 10.1107/S1600536811030133

Methyl 2,2′-dimethyl-4′-[2-(methylsulfanyl)ethyl]-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: PMC3200713 PMID: 22058900

Abstract

In the isoquinoline ring system of the title molecule, C₁₈H₂₀N₂O₅S, the fused N-heterocyclic ring is distorted towards a half-boat conformation. The methyl formate moiety is disordered over two sets of sites with refined occupancies of 0.882 (5) and 0.118 (5). In the crystal, molecules are linked via weak intermolecular C—H⋯O hydrogen bonds into one-dimensional chains along [010].

Related literature

For general background to and the biological activity of isoquinoline- and oxazole-containing compounds, see: Yu et al. (2010 ▶); Huang et al. (2011 ▶); Harris et al. (2005 ▶); Vintonyak et al. (2010 ▶); Badillo et al. (2010 ▶, 2011 ▶); Wang et al. (2010 ▶); Nair et al. (2002 ▶). For the stability of the temperature controller used for 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

C₁₈H₂₀N₂O₅S
M _r = 376.42
Monoclinic,
a = 15.0052 (15) Å
b = 8.4548 (8) Å
c = 15.4915 (15) Å
β = 114.621 (2)°
V = 1786.7 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.21 mm⁻¹
T = 100 K
0.18 × 0.17 × 0.14 mm

Data collection

Bruker APEXII DUO CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.963, T _max = 0.971
14571 measured reflections
4063 independent reflections
3343 reflections with I > 2σ(I)
R _int = 0.046

Refinement

R[F ² > 2σ(F ²)] = 0.042
wR(F ²) = 0.120
S = 1.03
4063 reflections
251 parameters
5 restraints
H-atom parameters constrained
Δρ_max = 0.37 e Å⁻³
Δρ_min = −0.32 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 datablock(s) global, I. DOI: 10.1107/S1600536811030133/lh5290sup1.cif

e-67-o2216-sup1.cif^{(23.5KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811030133/lh5290Isup2.hkl

e-67-o2216-Isup2.hkl^{(199.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811030133/lh5290Isup3.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
C18—H18C⋯O2ⁱ	0.96	2.49	3.436 (2)	167

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Symmetry code: (i) Inline graphic .

Acknowledgments

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

supplementary crystallographic information

Comment

Photocycloaddition of isoquinoline-1,3,4-trione combined with following transformation of the photocycloadducts has become facile method to build various scaffold containing isoquinoline moiety (Yu et al., 2010; Huang et al., 2011). Oxazoles can be used to inhibit the activity of malignant tumors (Harris et al., 2005). Spirocyclic oxindoles have emerged as attractive synthetic targets because of their prevalence in numerous natural products and important biological activity (Badillo et al., 2010; Vintonyak et al., 2010). Among them, the synthesis of spirooxindole oxazoles is of great intrest (Badillo et al., 2011; Wang et al., 2010; Nair et al., 2002). Many bioactive natural products especially alkaloids contain an isoquinoline or oxazole ring. It is necessary to develop methodologies to construct such moieties. The title compound which was derived from isoquinoline-1,3,4-trione and an oxazole and may have potential use in biochemical and pharmaceutical fields.

In the racemic title compound, Fig. 1, atoms C9 and C11 are the chiral centers. 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 0.213 (2) Å from the mean plane through the remaining atoms, puckering parameters (Cremer & Pople, 1975) Q = 0.3237 (18) Å, Θ = 67.0 (3)° and φ = 102.1 (3)°. Bond lengths (Allen et al., 1987) and angles are within normal ranges and comparable to related structures (Fun et al., 2011a, b, c, d). The methyl formate moiety (O4/O5/C15/C16) is disordered over two positions with refined site-occupancies of 0.882 (5) and 0.118 (5).

In the crystal, Fig. 2, molecules are linked via intermolecular C18–H18C···O2ⁱ hydrogen bonds (Table 1) into infinite one-dimensional chains along [010].

Experimental

The title compound was the main product from the acid-catalyzed transformation of the photocyclo adduct of isoquinoline-1,3,4-trione and 4-(2-(methylthio)ethyl)-5-methoxy-2-methyloxazole. The compound was purified by flash column chromatography with ethyl acetate/petroleum ether (1:4) as eluents. X-ray quality crystals of the title compound were obtained from slow evaporation of an acetone and petroleum ether solution (1:5) of the title compound (m.p. 440-142 K).