(5R)-3-(2-Chloro­acet­yl)-4-methyl-5-phenyl-1,3,4-oxadiazinan-2-one

Ignez Caracelli; Daniel C S Coelho; Paulo R Olivato; Alessandro Rodrigues; Edward R T Tiekink

doi:10.1107/S1600536811020356

. 2011 Jun 4;67(Pt 7):o1571–o1572. doi: 10.1107/S1600536811020356

(5R)-3-(2-Chloroacetyl)-4-methyl-5-phenyl-1,3,4-oxadiazinan-2-one

Ignez Caracelli ^a,^*, Daniel C S Coelho ^b, Paulo R Olivato ^c, Alessandro Rodrigues ^d, Edward R T Tiekink ^e

PMCID: PMC3152093 PMID: 21836983

Abstract

The 1,3,4-oxadiazinan-2-one ring in the title compound, C₁₂H₁₃ClN₂O₃, is in a distorted half-chair conformation. The phenyl and chloroacetyl groups occupy axial and equatorial positions, respectively, and lie to the opposite side of the molecule to the N-bound methyl substituent. Molecules are consolidated in the crystal structure by C—H⋯O interactions.

Related literature

For background to 1,3,4-oxadiazin-2-ones, see: Trepanier et al. (1968 ▶); Roussi et al. (1998 ▶, 1999 ▶, 2000 ▶); Casper et al. (2002a ▶,b ▶); Bonin et al. (2006 ▶). For a related structure, see: Zukerman-Schpector et al. (2009 ▶). For the synthesis, see: Rodrigues et al. (2005 ▶). For conformational analysis, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₁₂H₁₃ClN₂O₃
M _r = 268.69
Orthorhombic,
a = 9.4862 (2) Å
b = 9.6237 (2) Å
c = 13.2433 (3) Å
V = 1209.01 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.32 mm⁻¹
T = 100 K
0.35 × 0.30 × 0.25 mm

Data collection

Bruker APEXII CCD diffractometer
29813 measured reflections
2378 independent reflections
2334 reflections with I > 2σ(I)
R _int = 0.026

Refinement

R[F ² > 2σ(F ²)] = 0.020
wR(F ²) = 0.054
S = 1.07
2378 reflections
164 parameters
H-atom parameters constrained
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.20 e Å⁻³
Absolute structure: Flack (1983 ▶), 993 Friedel pairs
Flack parameter: 0.01 (5)

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and DIAMOND (Brandenburg, 2006 ▶); software used to prepare material for publication: MarvinSketch (Chemaxon, 2010 ▶) and publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811020356/hg5045sup1.cif

e-67-o1571-sup1.cif^{(17.7KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811020356/hg5045Isup2.hkl

e-67-o1571-Isup2.hkl^{(114.5KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811020356/hg5045Isup3.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
C2—H2⋯O3ⁱ	1.00	2.60	3.5142 (15)	153
C8—H8⋯O2ⁱⁱ	0.95	2.60	3.2689 (16)	128
C11—H11b⋯O2ⁱⁱⁱ	0.99	2.54	3.3675 (16)	141
C12—H12a⋯O2ⁱⁱⁱ	0.98	2.57	3.5448 (16)	173

Open in a new tab

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

Acknowledgments

We thank the Brazilian agencies FAPESP, CNPq (fellowships 308116/2010–0 to IC and 303544/2009–0 to PRO) and CAPES (808/2009 to IC) for financial support. We also thank Dr Charles H. Lake from Indiana University of Pennsylvania for the data collection during the American Crystallographic Association Summer Course in small molecule crystallography.

supplementary crystallographic information

Comment

About forty years ago Trepanier and collaborators reported the first synthesis of some 3,4,5,6-tetrahydro-2H-1,3,4-oxadiazin-2-ones as candidates for central nervous system stimulant activity (Trepanier et al., 1968). After three decades from the discovery of 1,3,4-oxadiazin-2-ones, Husson, Micouin and co-workers (Roussi et al., 1998) successfully employed this class of compound as chiral auxiliaries in diastereoselective alkylations and in dipolar cycloadditions (Roussi et al., 1999, 2000, Bonin et al., 2006). In a different approach, Hitchcock and collaborators have been successfully applying 1,3,4-oxadiazinan-2-one derivatives as chiral auxiliaries in asymmetric aldol addition reactions (Casper et al., 2002b). Besides their applications in asymmetric synthesis, this class of compounds show a very interesting conformational behaviour (Casper et al., 2002a). To explore the adopted conformation of the title compound, (I), in the solid-state, an X-ray study was performed.

The crystal structure analysis of (I) confirms the R configuration at atom C2, Fig. 1, in accord with expectation from the synthesis. The 1,3,4-oxadiazinan-2-one ring is in a distorted half-chair conformation, as shown by the ring-puckering parameters: q₂ = 0.364 (1) Å, q₃ = -0.333 (1) Å, Q = 493 (1) Å and φ₂ = 32.0 (2) ° (Cremer and Pople, 1975). The deviations of the O1, C1, N1, N2, C2 and C3 atoms from their least-squares plane are 0.0424 (10) -0.0497 (13), -0.1285 (11), 0.3139 (11), -0.3212 (13) and 0.1430 (13) Å, respectively. The observed conformation contrasts the twisted chair conformation found in the only other single-ring 1,3,4-oxadiazinan-2-one structure known (Zukerman-Schpector et al., 2009). The chloridoacetyl and phenyl groups lie to the same side of the molecule and opposite to that of the N-bound methyl group. The dihedral angles formed between the 1,3,4-oxadiazinan-2-one ring and the phenyl and chloridoacetyl (Cl,O3,C10,C11) groups are 87.69 (6) and 14.41 (3) °, respectively, consistent with axial and equatorial substitution. Molecules are consolidated in the crystal packing by C—H···O interactions operating in three-dimensions, Table 1 and Fig. 2.

Experimental

The starting (R)-4-methyl-5-phenyl-1,3,4-oxadiazinan-2-one was synthesized by using the same procedure as previously reported (Rodrigues et al. 2005). The chlorooacetyl-1,3,4-oxadiazinan-2-one (I) species was prepared by the acylation reaction of 1,3,4-oxadiazinan-2-one. A solution of BuLi (2.00 M in hexane, 1.45 ml, 2.86 mmol) was added drop wise to a solution of 1,3,4-oxadiazinan-2-one (500 mg, 2.60 mmol) in dry THF (10 ml) at 195 K and the reaction was stirred for an additional 15 min. A chloroacetyl chloride (230 µL, 2.86 mmol) solution in THF (1 ml) was added slowly to the reaction mixture. After 15 min, the light-yellow solution was warmed to RT for a further 30 min. The reaction was quenched with saturated aqueous ammonium chloride solution (5 ml). The mixture was concentrated under reduced pressure, taken up in water (5 ml) and extracted with DCM (3 times; 15 ml) then dried (MgSO₄). Evaporation of the solvent in vacuo gave the crude product which was purified by flash column chromatography on silica gel with 40% EtOAc in hexanes to give the pure product as a colourless solid (572 mg, 82%). Colourless crystals of (I) were obtained by vapour diffusion from hexane/acetone at 298 K. mp = 408 – 410 K; [α]_D²⁵ +52,5° (c 1,02, CHCl₃); ¹H NMR (500 MHz, CDCl₃/TMS), δ (p.p.m.): 7.40–7.35 (m, 5H), 4.88 (dd, ²J = 11.5 Hz, ³J = 5.3 Hz, 1H), 4.77 (dd, ²J = 11.5 Hz, ³J = 7.7 Hz, 1H), 4.43 (AB spin system, Dn = 36.0 Hz, ²J = 15.3 Hz, 2H), 4.40 (dd, ³J = 7.7 Hz, ³J = 5.3 Hz, 1H), 2.81 (s, 3H). ¹H NMR (125 MHz, CDCl₃/TMS), δ (p.p.m.): 166.07, 149.54, 134.69, 129.16, 128.90, 127.02, 67.65, 61.54, 44.75, 42.12. Anal. calcd for C₁₂H₁₃ClN₂O₃: C, 53.64%; H, 4.88%; N, 10.43%. Found: C, 53.46%; H, 4.92%; N, 10.49%.