2-(Furan-2-yl)-5-(2-nitro­benz­yl)-2,3-dihydro-1,5-benzothia­zepin-4(5H)-one

Zhao-Hui Huang; Yong Chu; De-Yong Ye

doi:10.1107/S1600536810052098

. 2010 Dec 18;67(Pt 1):o168. doi: 10.1107/S1600536810052098

2-(Furan-2-yl)-5-(2-nitrobenzyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one

Zhao-Hui Huang ^a, Yong Chu ^a, De-Yong Ye ^a,^*

PMCID: PMC3050135 PMID: 21522675

Abstract

The title compound, C₂₀H₁₆N₂O₄S, was prepared by introduction of a 2-nitrobenzyl group to 2-(furan-2-yl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one via an alkaline-catalysed reaction. The thiazepine ring adopts a twist-boat conformation. The furan ring is oriented at dihedral angles of 56.75 (14) and 10.82 (14)° with respect to the two benzene rings, while the two benzene rings make a dihedral angle of 62.96 (10)°. Weak intermolecular C—H⋯O hydrogen bonds occur in the crystal structure.

Related literature

The title compound was prepared as part of an investigation of novel GSK 3β inhibitors. For applications of non-ATP competitive glycogen synthase kinase 3β(GSK 3β) inhibitors, see: Martinez et al. (2002 ▶).

Experimental

Crystal data

C₂₀H₁₆N₂O₄S
M _r = 380.41
Monoclinic,
a = 11.061 (3) Å
b = 8.538 (3) Å
c = 19.340 (6) Å
β = 105.535 (4)°
V = 1759.7 (9) Å³
Z = 4
Mo Kα radiation
μ = 0.21 mm⁻¹
T = 293 K
0.18 × 0.16 × 0.14 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.963, T _max = 0.971
7699 measured reflections
3458 independent reflections
2755 reflections with I > 2σ(I)
R _int = 0.038

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.140
S = 1.10
3458 reflections
244 parameters
12 restraints
H-atom parameters constrained
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.34 e Å⁻³

Data collection: SMART (Bruker, 2000 ▶); cell refinement: SAINT (Bruker, 2000 ▶); 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.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810052098/xu5112sup1.cif

e-67-0o168-sup1.cif^{(18.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810052098/xu5112Isup2.hkl

e-67-0o168-Isup2.hkl^{(169.6KB, hkl)}

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
C2—H2A⋯O2ⁱ	0.93	2.49	3.401 (3)	168
C12—H12A⋯O2ⁱⁱ	0.93	2.59	3.381 (3)	144

Open in a new tab

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

Acknowledgments

The authors acknowledge Dr Z. Chen for fruitful discussions and the Department of Chemistry, Fudan University, for the data collection.

supplementary crystallographic information

Comment

Non-ATP competitive glycogen synthase kinase 3β(GSK 3β) inhibitors might have therapeutic potential for the treatment of diabetes, Alzheimer's disease and cancer (Martinez et al., 2002). The title compound, 5-(2-nitrobenzyl)-2-(furan-2-yl)-2,3-[b][1,4]thiazepin-4(5H)-one(I), was obtained in our research for novel GSK 3β inhibitors. We report here the crystal structure of the title compound in order to study the relationship between its structure and GSK 3β inhibitory activity.

The molecular structure of the title compound presented on Fig.1. In the crystal structure, the thiazepine ring adopts a similar boat form, while the dihedral angles between the furan ring and the C8>C13, C15>C20 benzene rings are 56.7° and 10.7°, respectively. The dihedral angle between C8>C13 and C15>C20 benzene rings is 63.0°. The crystal packing is stabilized by C—H···O and C—H···N hydrogen bonds (Table 1).

Experimental

A mixture of 2-(furan-2-yl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one (495 mg, 2 mmol) and 60% sodium hydride (240 mg, 6 mmol) in dry N,N-dimethylformamide (8 ml) was stirred in ice water bath for 30 minutes, then a solution of 1-(bromomethyl)-2-nitrobenzene (864 mg, 6 mmol) in dry N,N-Dimethylformamide (6 ml) was added and the resulted mixture was stirred for another 30 minutes. The target compound was extracted by ethyl acetate. After the ethyl acetate evaporated in vacuo, the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 3) to afford 577 mg of (I), yield 76%. Recrystallization from methanol gave light yellow crystals.