3-Chloro­methyl-6,7-dimethyl-1,2-benz­oxazole

M Kayalvizhi; G Vasuki; A Veerareddy; G Laxminarasimha

doi:10.1107/S1600536812039700

. 2012 Sep 26;68(Pt 10):o3008. doi: 10.1107/S1600536812039700

3-Chloromethyl-6,7-dimethyl-1,2-benzoxazole

M Kayalvizhi ^a, G Vasuki ^a,^*, A Veerareddy ^b, G Laxminarasimha ^b

PMCID: PMC3470366 PMID: 23125779

Abstract

In the title compound, C₁₀H₁₀ClNO, the benzoisoxazole ring is almost planar (r.m.s. deviation = 0.0121 Å) and the chloro substituent in the side chain is anticlinal relative to the N—C bond of the isoxazole ring. In the crystal, adjacent molecules are linked via a pair of weak C—H⋯N hydrogen bonds, forming dimers through a cyclic R ₂ ²(8) association.

Related literature

For the biological and chemical applications of benzoxazoles, see: Ha et al. (2010 ▶); Kayalvizhi et al. (2011 ▶); Krishnaiah et al. (2009 ▶); Qu et al. (2008 ▶); Raju et al. (2002 ▶); Veerareddy et al. (2011 ▶). For graph-set analysis, see: Bernstein et al. (1995 ▶).

Experimental

Crystal data

C₁₀H₁₀ClNO
M _r = 195.64
Monoclinic,
a = 20.4938 (15) Å
b = 4.1237 (3) Å
c = 24.6361 (18) Å
β = 114.151 (3)°
V = 1899.8 (2) Å³
Z = 8
Mo Kα radiation
μ = 0.36 mm⁻¹
T = 295 K
0.20 × 0.15 × 0.15 mm

Data collection

Bruker Kappa APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1999 ▶) T _min = 0.932, T _max = 0.948
8155 measured reflections
1748 independent reflections
1396 reflections with I > 2σ(I)
R _int = 0.035

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.120
S = 1.06
1748 reflections
120 parameters
H-atom parameters constrained
Δρ_max = 0.25 e Å⁻³
Δρ_min = −0.19 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: APEX2 and SAINT (Bruker, 2004 ▶); data reduction: SAINT and XPREP (Bruker, 2004 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812039700/zs2231sup1.cif

e-68-o3008-sup1.cif^{(18.3KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812039700/zs2231Isup2.hkl

e-68-o3008-Isup2.hkl^{(86.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812039700/zs2231Isup3.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
C10—H10B⋯N2ⁱ	0.97	2.55	3.479 (3)	160

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank the Sophisticated Analytical Instrument Facility, IIT-Madras, Chennai, for the single-crystal X-ray data collection.

supplementary crystallographic information

Comment

The benzoxazole ring system is one of the most common heterocycles in medicinal chemistry (Qu et al., 2008). Isoxazole derivatives bearing various substituents are known to have diverse biological activities in pharmaceutical and agricultural areas (Ha et al., 2010). In agriculture applications herbicidal activity has been identified (Raju et al., 2002) as well as fungicidal activities against some plant pathogens (Ha et al., 2010). Some derivatives are also used as semiconductors and as corrosion inhibitors in fuels and lubricants (Raju et al., 2002). They are also important intermediates in the synthesis of many complex natural products (Krishnaiah et al., 2009). Among these compounds, 3-substituted-1,2-benzisoxazole and its derivatives are emerging as potential antipsychotic compounds (Kayalvizhi et al., 2011). Substituted benzoxazoles have been reported to possess diverse chemotherapeutic properties including antibiotic, antimicrobial, antiviral, antitumor and other pharmacological activities (Qu et al., 2008; Krishnaiah et al., 2009). With its extensive uses as a drug for epilepsy, its cost-effective synthesis remained a great challenge for synthetic organic chemists (Veerareddy et al., 2011). In a search for new benzisoxazole compounds with better biological activity, the title compound, C₁₀H₁₀ClNO, was synthesized and its crystal structure determined, in order to examine the structure–activity effects of the chloromethyl and 6,7-dimethyl substituents on the benzoisoxazole ring.

In the structure of the title compound (Fig. 1) the benzoisoxazole ring is planar with a root mean square deviation of 0.0121 Å. The torsion angle [N2—C3—C10—Cl = 121.31 (19)°] indicates that the side chain is anticlinal looking down the C3—C10 bond. The exocyclic angles C10—C3—C3a [129.35 (19)°] and C3—C3a—C4 [137.13 (19)°] deviate significantly from the normal values and this may be due to the intramolecular non-bonded interaction between the chlorine atom and an aromatic H atom [Cl···H4 = 3.2582 (8) Å]. In the crystal, adjacent molecules are linked via a pair of weak intermolecular C—H···N hydrogen bonds (Table 1) forming dimers through a cyclic R²₂(8) association (Bernstein et al., 1995) (Fig. 2).

Experimental

To a solution of 3,6,7-trimethylbenzo[d]isoxazole-2-oxide (1.0 mol) in methylene dichloride (10 ml) was added POCl₃ (2.0 mol) dropwise at 20°C over a period of 5 min and stirred for 5 min also at 20°C. Triethylamine (2.0 mol) was then added dropwise at 20°C over a period of 10 min at such a rate that the reaction temperature did not exceed 30°C. The mixture was then stirred at reflux temperature for 48 h and cooled to 10°C. The reaction mixture was washed with chilled water, followed by addition of a 10% Na₂CO₃ solution to obtain a neutral pH. The aqueous layer was re-extracted with methylene chloride (2 × 100 ml). The combined organic layer was dried over anhydrous Na₂SO₄ and the solvent was removed under vacuum to give the crude product, which was purified by column chromatography and by crystallization (Veerareddy et al., 2011).