(5S,6R)-4,5-Di­methyl-6-phenyl-3-tri­methyl­acetyl-2H-1,3,4-oxadiazinan-2-one

The crystal structure of the title compound, C₁₆H₂₂N₂O₃, was undertaken in the course of a study on an acyl­ated pseudoephedrine-derived 1,3,4-oxadiazinan-2-one. The conformation adopted by this heterocycle is a contorted half-chair, in which the imide carbonyls are arranged with the carbonyl groups oriented approximately syn to each other. The torsion angle between the imide carbonyl groups is 37.6 (2)°.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.036
• wR factor = 0.097
• Data-to-parameter ratio = 9.2

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry

General Notes



REFLT_03
         From the CIF: _diffrn_reflns_theta_max           25.79
         From the CIF: _reflns_number_total               1792
         Count of symmetry unique reflns         1791
         Completeness (_total/calc)            100.06%
         TEST3: Check Friedels for noncentro structure
         Estimate of Friedel pairs measured         1
         Fraction of Friedel pairs measured     0.001
         Are heavy atom types Z>Si present           no
          Please check that the estimate of the number of Friedel pairs is
          correct. If it is not, please give the correct count in the
          _publ_section_exptl_refinement section of the submitted CIF.

---

S1. Comment

Chiral non-racemic oxazolidin-2-ones serve as chiral auxiliaries in asymmetric transformations, most notably in the aldol addition reaction (Evans et al., 2002; Crimmins et al., 2001; Ager et al., 1997); however, the related 1,3,4-oxadiazinan-2-one heterocycles have received little notice since their disclosure (Trepanier et al., 1968). Recently, 1,3,4-oxadiazinan-2-ones were successfully employed as chiral auxiliaries in dipolar cycloadditions (Roussi et al., 2000) and in diastereoselective alkylations (Roussi et al., 1998). We have conducted synthetic (Hitchcock et al., 2001) and conformational studies (Casper et al., 2002) of 1,3,4-oxadiazinan-2-one derivatives.

Herein we report the X-ray structure of the N₃-trimethylacetyl derivatized pseudoephedrine-derived 1,3,4-oxadiazinan-2-one (I). The structure of (I) nominally exhibits syn-parallel carbonyls, consistent with our recently reported acetyl and propionyl variants. Crystallographic analysis of these latter two compounds revealed that these heterocycles adopt twist–boat conformations in which the imide carbonyl groups are arranged syn–parallel, as evidenced by the 3.1 (2) (acetyl) and 3.3 (1)° (propionyl) torsion angles between carbonyl groups (Casper et al., 2002). Similarly, the N₃-trimethylacetyl derivative displays imide carbonyl groups tending towards a syn–parallel orientation, with an O21—C2—C15—O16 torsion angle of 37.6 (2)°. Remarkably, rather than maintaining the acetyl and propionyl derivatives' twist–boat conformation by allowing the trimetylacetyl carbonyl group to rotate to an antiparallel orientation, to alleviate N₄-methyl and tert-butyl steric interactions, compound (I) adopts a contorted half-chair conformation, in which the imide carbonyl groups remain arranged with the carbonyl groups oriented in the same direction. Compound (I) displays a torsion angle of 154.2 (2)° for N4—N3—C2—O21, while values of 175.8 (2) and 178.6 (1)° are observed in the respective N₃-acetyl and the N₃-propionyl variants. Based on the amount of distortion of the π system and ¹³C NMR analysis, it is possible this is not the structure idealized in solution. As noted in other oxadiazinanone systems, the N₃-substituent is rigidly held, while the N₄-methyl group must rearrange to relieve allylic strain (Casper et al., 2002). Noteworthy is the X-ray structure of the ephedrine (C₆-epimer of related pseudoephedrine) based N₃-phenylacetylated oxadiazinanone, which also displays syn-parallel imide carbonyl groups, torsion angle of 19.5 (4)° (Hitchcock et al., 2001). These four structures suggest the syn–parallel conformation is strongly preferred for the carbonyl moieties of 1,3,4-oxadiazinan-2-ones. The predominance of the parallel arrangement is remarkable in that the antiparallel conformation is observed in the related N₃-acyloxazolidin-2-ones (Evans et al., 1981) and should be energetically favorable based on a reduced dipole moment. The title compound crystallized in the orthorhombic space group P2₁2₁2₁ (McArdle, 1996) and stacks with the phenyl substituents superimposed along and parallel with the stacking axis (Fig 2). The closest intermolecular interactions are H6···O21ⁱ of 2.46 Å and H18A···N4 of 2.45 Å [symmetry code: (i) −1/2 + x, 1/2 − y, 1 − z]. Neither of these or other intermolecular interactions seem particularly relevant to attributing packing arguments as explanation of the dicarbonyl conformation.

S2. Experimental

The title compound was prepared by acylation of pseudoephedrine derived 1,3,4-oxadiazinan-2-one using sodium hydride and trimethylacetylchloride (Casper et al., 2002). Colorless clear single crystals were grown by vapor diffusion of cyclohexane into dichloromethane at 269 K. For data collection, a sample crystal was glued to the end of a glass fiber.

S3. Refinement

All hydrogen atoms were included in the refinement in the riding model approximation, with isotropic displacement parameters fixed at 1.2U_eq of the parent atom. No evidence for disorder or included solvents was identified through difference Fourier synthesis. While 1320 Friedel equivalent pairs were measured, the use of Mo radiation with the exclusively light atom sample precluded the calculation of a meaningful Flack parameter (Flack et al., 2000). The absolute structure was inferred from the chiral chemical precursors.

Computing details

Data collection: CAD-4 EXPRESS (Enraf-Nonius, 1994); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SIR92 (Altomare, 1993); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and Mercury1.1 (Bruno et al., 2002); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures

	Fig. 1. Perspective view of (I), showing the atom-labeling scheme. Non-H atoms are represented by ellipsoids at the 50% probability level. H atoms have been drawn arbitrarily small and are not labeled.
	Fig. 2. The molecular packing of (I), viewed along the a axis.

(I)

Crystal data

C16H22N2O3	F(000) = 624
Mr = 290.36	Dx = 1.192 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 23 reflections
a = 10.1079 (7) Å	θ = 10.8–16.7°
b = 11.4087 (10) Å	µ = 0.08 mm^−1
c = 14.0354 (9) Å	T = 293 K
V = 1618.5 (2) Å^3	Block, colorless
Z = 4	0.76 × 0.72 × 0.4 mm

Data collection

Enraf-Nonius CAD-4 diffractometer	Rint = 0.057
non–profiled ω/2θ scans	θmax = 25.8°, θmin = 2.3°
Absorption correction: ψ scan (North et al., 1968)	h = 0→12
Tmin = 0.953, Tmax = 0.967	k = −13→13
3414 measured reflections	l = 0→17
1792 independent reflections	3 standard reflections every 120 min
1484 reflections with I > 2σ(I)	intensity decay: 4%

Refinement

Refinement on F^2	0 restraints
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.036	w = 1/[σ^2(Fo^2) + (0.052P)^2 + 0.0905P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.097	(Δ/σ)max < 0.001
S = 1.04	Δρmax = 0.13 e Å^−3
1792 reflections	Δρmin = −0.17 e Å^−3
195 parameters

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.45022 (15)	0.12416 (15)	0.45945 (9)	0.0526 (4)
C2	0.5757 (2)	0.15263 (18)	0.47948 (14)	0.0430 (5)
N3	0.61434 (16)	0.14665 (16)	0.57649 (11)	0.0421 (4)
N4	0.51348 (15)	0.15535 (15)	0.64721 (12)	0.0401 (4)
C5	0.41482 (19)	0.06400 (17)	0.62660 (13)	0.0398 (4)
H5	0.4613	−0.0113	0.6239	0.048*
C6	0.3512 (2)	0.08480 (18)	0.52927 (14)	0.0418 (4)
H6	0.2855	0.1474	0.5364	0.05*
C7	0.28190 (19)	−0.02082 (18)	0.49006 (14)	0.0436 (5)
C8	0.3507 (3)	−0.1174 (2)	0.45725 (17)	0.0588 (6)
H8	0.4427	−0.1153	0.4552	0.071*
C9	0.2844 (3)	−0.2174 (2)	0.4272 (2)	0.0759 (8)
H9	0.3317	−0.282	0.4055	0.091*
C10	0.1474 (4)	−0.2203 (3)	0.4299 (2)	0.0823 (9)
H10	0.1027	−0.2874	0.4105	0.099*
C11	0.0777 (3)	−0.1251 (3)	0.46091 (19)	0.0770 (9)
H11	−0.0143	−0.1273	0.4618	0.092*
C12	0.1435 (2)	−0.0256 (2)	0.49099 (16)	0.0559 (6)
H12	0.0954	0.0388	0.5121	0.067*
C13	0.3097 (2)	0.0551 (2)	0.70436 (15)	0.0569 (6)
H13A	0.3519	0.0447	0.765	0.068*
H13B	0.2531	−0.0106	0.6916	0.068*
H13C	0.258	0.1257	0.7053	0.068*
C14	0.4607 (2)	0.27577 (19)	0.65025 (17)	0.0540 (5)
H14A	0.5314	0.3297	0.663	0.065*
H14B	0.3954	0.2815	0.6997	0.065*
H14C	0.4209	0.2945	0.59	0.065*
C15	0.7424 (2)	0.10673 (19)	0.60147 (15)	0.0474 (5)
O16	0.81299 (18)	0.0701 (2)	0.53886 (13)	0.0816 (6)
C17	0.7863 (2)	0.1090 (2)	0.70626 (15)	0.0509 (5)
C18	0.7154 (3)	0.0112 (3)	0.76160 (19)	0.0695 (7)
H18A	0.6221	0.0271	0.7632	0.083*
H18B	0.7491	0.0081	0.8255	0.083*
H18C	0.7305	−0.0626	0.7306	0.083*
C19	0.7650 (3)	0.2290 (3)	0.75227 (18)	0.0747 (7)
H19A	0.8002	0.2889	0.7115	0.09*
H19B	0.8094	0.2314	0.8127	0.09*
H19C	0.6721	0.242	0.7615	0.09*
C20	0.9354 (2)	0.0816 (3)	0.7064 (2)	0.0772 (8)
H20A	0.9501	0.006	0.6782	0.093*
H20B	0.9675	0.0814	0.7708	0.093*
H20C	0.9815	0.1403	0.6703	0.093*
O21	0.64693 (17)	0.18500 (15)	0.41656 (11)	0.0579 (4)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0490 (8)	0.0643 (10)	0.0446 (7)	−0.0120 (7)	−0.0036 (6)	0.0099 (7)
C2	0.0455 (11)	0.0375 (9)	0.0459 (10)	−0.0020 (9)	0.0038 (9)	0.0013 (9)
N3	0.0369 (8)	0.0478 (9)	0.0415 (8)	0.0018 (7)	0.0036 (7)	−0.0010 (8)
N4	0.0370 (8)	0.0394 (8)	0.0440 (8)	0.0035 (7)	0.0034 (7)	−0.0042 (7)
C5	0.0373 (9)	0.0380 (9)	0.0442 (9)	0.0028 (8)	0.0021 (8)	−0.0001 (8)
C6	0.0380 (10)	0.0422 (10)	0.0454 (10)	0.0013 (9)	0.0029 (8)	0.0034 (8)
C7	0.0438 (11)	0.0453 (10)	0.0416 (10)	−0.0017 (9)	−0.0014 (9)	0.0021 (8)
C8	0.0595 (13)	0.0561 (13)	0.0607 (13)	0.0062 (12)	−0.0074 (11)	−0.0086 (11)
C9	0.108 (2)	0.0516 (13)	0.0685 (16)	0.0010 (16)	−0.0132 (17)	−0.0101 (13)
C10	0.104 (2)	0.0735 (19)	0.0696 (17)	−0.041 (2)	−0.0156 (17)	0.0003 (15)
C11	0.0651 (16)	0.099 (2)	0.0664 (15)	−0.0359 (17)	−0.0017 (14)	0.0058 (16)
C12	0.0447 (11)	0.0681 (14)	0.0550 (12)	−0.0062 (12)	0.0038 (10)	0.0019 (12)
C13	0.0499 (12)	0.0709 (15)	0.0498 (12)	−0.0028 (12)	0.0071 (10)	0.0005 (11)
C14	0.0554 (13)	0.0420 (11)	0.0645 (13)	0.0076 (10)	−0.0017 (11)	−0.0097 (10)
C15	0.0394 (9)	0.0476 (11)	0.0552 (11)	0.0019 (9)	0.0058 (9)	0.0038 (9)
O16	0.0613 (10)	0.1188 (16)	0.0646 (10)	0.0366 (12)	0.0103 (9)	−0.0024 (11)
C17	0.0437 (11)	0.0556 (12)	0.0534 (11)	0.0005 (11)	−0.0024 (10)	0.0089 (10)
C18	0.0638 (14)	0.0750 (16)	0.0697 (15)	0.0002 (15)	0.0014 (13)	0.0284 (13)
C19	0.0792 (17)	0.0752 (17)	0.0698 (15)	−0.0067 (16)	−0.0184 (16)	−0.0104 (14)
C20	0.0470 (12)	0.105 (2)	0.0795 (17)	0.0067 (15)	−0.0079 (13)	0.0156 (18)
O21	0.0558 (8)	0.0687 (10)	0.0492 (7)	−0.0102 (8)	0.0072 (8)	0.0080 (7)

Geometric parameters (Å, º)

O1—C2	1.339 (3)	C11—H11	0.93
O1—C6	1.471 (2)	C12—H12	0.93
C2—O21	1.198 (3)	C13—H13A	0.96
C2—N3	1.418 (3)	C13—H13B	0.96
N3—C15	1.416 (3)	C13—H13C	0.96
N3—N4	1.426 (2)	C14—H14A	0.96
N4—C5	1.471 (3)	C14—H14B	0.96
N4—C14	1.474 (3)	C14—H14C	0.96
C5—C13	1.526 (3)	C15—O16	1.207 (3)
C5—C6	1.528 (3)	C15—C17	1.536 (3)
C5—H5	0.98	C17—C19	1.529 (4)
C6—C7	1.499 (3)	C17—C18	1.537 (3)
C6—H6	0.98	C17—C20	1.538 (3)
C7—C8	1.382 (3)	C18—H18A	0.96
C7—C12	1.400 (3)	C18—H18B	0.96
C8—C9	1.389 (4)	C18—H18C	0.96
C8—H8	0.93	C19—H19A	0.96
C9—C10	1.387 (5)	C19—H19B	0.96
C9—H9	0.93	C19—H19C	0.96
C10—C11	1.365 (5)	C20—H20A	0.96
C10—H10	0.93	C20—H20B	0.96
C11—C12	1.382 (4)	C20—H20C	0.96
C2—O1—C6	125.36 (15)	C5—C13—H13A	109.5
O21—C2—O1	119.31 (19)	C5—C13—H13B	109.5
O21—C2—N3	123.8 (2)	H13A—C13—H13B	109.5
O1—C2—N3	116.80 (17)	C5—C13—H13C	109.5
C15—N3—C2	120.33 (16)	H13A—C13—H13C	109.5
C15—N3—N4	120.22 (16)	H13B—C13—H13C	109.5
C2—N3—N4	117.89 (16)	N4—C14—H14A	109.5
N3—N4—C5	107.36 (14)	N4—C14—H14B	109.5
N3—N4—C14	110.09 (16)	H14A—C14—H14B	109.5
C5—N4—C14	114.87 (16)	N4—C14—H14C	109.5
N4—C5—C13	112.22 (16)	H14A—C14—H14C	109.5
N4—C5—C6	110.55 (15)	H14B—C14—H14C	109.5
C13—C5—C6	110.89 (17)	O16—C15—N3	118.1 (2)
N4—C5—H5	107.7	O16—C15—C17	122.1 (2)
C13—C5—H5	107.7	N3—C15—C17	119.72 (18)
C6—C5—H5	107.7	C19—C17—C15	112.26 (19)
O1—C6—C7	108.59 (16)	C19—C17—C18	111.8 (2)
O1—C6—C5	110.89 (15)	C15—C17—C18	109.68 (19)
C7—C6—C5	113.58 (16)	C19—C17—C20	108.6 (2)
O1—C6—H6	107.9	C15—C17—C20	106.3 (2)
C7—C6—H6	107.9	C18—C17—C20	108.0 (2)
C5—C6—H6	107.9	C17—C18—H18A	109.5
C8—C7—C12	118.4 (2)	C17—C18—H18B	109.5
C8—C7—C6	121.87 (19)	H18A—C18—H18B	109.5
C12—C7—C6	119.7 (2)	C17—C18—H18C	109.5
C7—C8—C9	120.9 (3)	H18A—C18—H18C	109.5
C7—C8—H8	119.6	H18B—C18—H18C	109.5
C9—C8—H8	119.6	C17—C19—H19A	109.5
C10—C9—C8	119.6 (3)	C17—C19—H19B	109.5
C10—C9—H9	120.2	H19A—C19—H19B	109.5
C8—C9—H9	120.2	C17—C19—H19C	109.5
C11—C10—C9	120.3 (3)	H19A—C19—H19C	109.5
C11—C10—H10	119.8	H19B—C19—H19C	109.5
C9—C10—H10	119.8	C17—C20—H20A	109.5
C10—C11—C12	120.1 (3)	C17—C20—H20B	109.5
C10—C11—H11	119.9	H20A—C20—H20B	109.5
C12—C11—H11	119.9	C17—C20—H20C	109.5
C11—C12—C7	120.7 (3)	H20A—C20—H20C	109.5
C11—C12—H12	119.6	H20B—C20—H20C	109.5
C7—C12—H12	119.6
C6—O1—C2—O21	−179.08 (19)	C5—C6—C7—C8	−71.3 (2)
C6—O1—C2—N3	−1.5 (3)	O1—C6—C7—C12	−131.0 (2)
O21—C2—N3—C15	−40.0 (3)	C5—C6—C7—C12	105.1 (2)
O1—C2—N3—C15	142.58 (19)	C12—C7—C8—C9	−0.9 (3)
O21—C2—N3—N4	154.2 (2)	C6—C7—C8—C9	175.6 (2)
O1—C2—N3—N4	−23.2 (3)	C7—C8—C9—C10	0.2 (4)
C15—N3—N4—C5	−110.60 (19)	C8—C9—C10—C11	0.7 (5)
C2—N3—N4—C5	55.2 (2)	C9—C10—C11—C12	−0.8 (5)
C15—N3—N4—C14	123.7 (2)	C10—C11—C12—C7	0.1 (4)
C2—N3—N4—C14	−70.5 (2)	C8—C7—C12—C11	0.8 (4)
N3—N4—C5—C13	173.32 (16)	C6—C7—C12—C11	−175.8 (2)
C14—N4—C5—C13	−63.9 (2)	C2—N3—C15—O16	−5.5 (3)
N3—N4—C5—C6	−62.32 (19)	N4—N3—C15—O16	160.0 (2)
C14—N4—C5—C6	60.5 (2)	C2—N3—C15—C17	175.66 (19)
C2—O1—C6—C7	−133.3 (2)	N4—N3—C15—C17	−18.8 (3)
C2—O1—C6—C5	−7.9 (3)	O16—C15—C17—C19	129.6 (3)
N4—C5—C6—O1	39.9 (2)	N3—C15—C17—C19	−51.6 (3)
C13—C5—C6—O1	164.97 (18)	O16—C15—C17—C18	−105.5 (3)
N4—C5—C6—C7	162.46 (16)	N3—C15—C17—C18	73.3 (3)
C13—C5—C6—C7	−72.4 (2)	O16—C15—C17—C20	11.0 (3)
O1—C6—C7—C8	52.5 (3)	N3—C15—C17—C20	−170.2 (2)