(Z)-α-5-Bromo-N-tert-butyl-2-methoxy­phenyl­nitrone

The title compound, C₁₂H₁₆BrNO₂, was synthesized in 95% yield by condensation of 5-bromo-2-methoxy­benzaldehyde and N-tert-butyl-hydroxy­lamine acetate in the presence of triethyl­amine as the base and anhydrous magnesium sulfate as the dehydrating agent. The C=N bond leads to a plane containing all atoms of the side chain, excluding the three methyl groups; this plane makes a dihedral angle of 14.44 (3)° with the ring plane.

Key indicators

• Single-crystal X-ray study
• T = 298 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.028
• wR factor = 0.081
• Data-to-parameter ratio = 14.8

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT431_ALERT_2_C Short Inter HL..A Contact  Br1    ..  O2      ..       3.18 Ang.

Alert level G
PLAT200_ALERT_1_G Check the Reported _diffrn_ambient_temperature .        293 K

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   1 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   0 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

Nitrones are versatile organic compounds widely used as 1,3-dipoles in cycloadditions (Merino & Padwa, 2004; Torsell, 1988), spin trapping agents in free radical chemistry (Janzen, 1971; Usuki et al., 2006) and also in biological studies (Zhang et al., 2000). Recently they have also been employed as therapeutics in age-related diseases (Floyd, 2006). Nitrones undergo many reactions, such as the Behrend Rearrangement, nitrone-oxime O-ether rearrangement, and thermolytic alkene elimination (Torsell, 1988). While the most conventional procedures for the preparation of nitrones have been the condensation of N-monosubstituted hydroxylamines with carbonyl compounds and the N-alkylation of oximes (Torsell, 1988), a newly reported high yielding and chemoselective procedure for the conversion of imines to nitrones using catalytic amounts of methyltrioxorhenium represents a breakthrough in nitrone synthesis (Soldaini et al., 2007). We have recently shown that nitrones derived from aromatic aldehydes can be used as convenient precursors to carbocyclic carbene ligands for the synthesis of novel and catalytically useful Pd compounds (Yao et al., 2007). The formation of nitrone-based Pd complexes involves the selective C—H activation of the aromatic ring via orthopalladation directed by the oxygen atom on the nitrone moiety. It can be expected that the stereochemistry around the C=N of the nitrone group would have a pronounced effect in formation of the C_carbene—Pd bond. For this purpose, we have synthesized the title compound, (I), and reported herein its crystal structure.

In the molecule of the title compound, (I), (Fig. 1) the bond lengths and angles are generally within normal ranges (Allen et al., 1987). The C8=N1 double bond leads to a plane containing C9, O2, N1, C8 and C5 atoms, and the dihedral angle between (C1—C6) ring and the plane of (N1/O2/C5/C8/C) is 14.44 (3)°.

Related literature

For general background, see: Merino & Padwa (2004); Torsell (1988); Janzen (1971); Usuki et al. (2006); Zhang et al. (2000); Floyd (2006); Soldaini et al. (2007); Yao et al. (2007). For bond- length data, see: Allen et al. (1987).

S2. Experimental

An oven-dried Schlenk flask was charged with 5-bromo-2-methoxybenzaldehyde (215 mg, 1.0 mmol), N-tert-butyl hydroxylamine acetate (298 mg, 2.0 mmol) and anhydrous magnesium sulfate (362 mg, 3.0 mmol) under argon. Triethylamine (350 µl, 253 mg, 2.5 mmol) was then added via syringe followed by anhydrous benzene (6 ml, distilled from sodium/benzophenone). After stirring at 363 K in a Schlenk flask for 15 d, the reaction mixture was filtered to remove the magnesium sulfate and the filtrate concentrated to dryness with a rotary evaporator. The crude mixture was purified by flash column chromatography on silica gel (60 230–400 mesh) using a 11:1 (v/v) dichloromethane/ethyl acetate solution as the eluent to give the title compound (yield; 270 mg, 95%, m.p. 372–373 K), as white solid. Crystals suitable for X-ray analysis were grown by slow solvent diffusion by layering hexane over a solution of the nitrone in dichloromethane. ¹H-NMR (500 MHz, in CDCl₃ at 25°C): δ 9.54 (1 H, d, J = 2.5 Hz), 7.95 (1 H, s), 7.36 (1H, dd, J = 2.5 and 8.5 Hz), 6.69 (1 H, d, J = 8.5 Hz), 3.80 (3H, s), 1.56 (9 H, s). 13 C-NMR (125 MHz, CDCl₃): δ156.0, 133.3, 130.7, 123.0, 121.9, 113.3, 111.3, 71.4, 55.9, 28.3. Anal. Calcd for C₁₂H₁₆BrNO₂: C, 50.37; H, 5.64; N, 4.89. Found: C, 50.34; H, 5.55; N 4.82.

S3. Refinement

H atoms were positioned geometrically with C—H = 0.93 and 0.96 Å for aromatic and methyl H atoms, respectively, and constrained to ride on their parent atoms, with U_iso(H) = xU_eq(C), where x = 1.2 for aromatic H and x = 1.5 for methyl H atoms.

Computing details

Data collection: SMART (Bruker, 1999); cell refinement: SAINT (Bruker, 1999); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Sheldrick, 1997); software used to prepare material for publication: SHELXTL.

Figures

Fig. 1.

(Z)-α-5-Bromo-N-tert-butyl-2-methoxyphenylnitrone

Crystal data

C12H16BrNO2	F(000) = 584
Mr = 286.17	Dx = 1.508 Mg m^−3
Monoclinic, P21/c	Melting point = 372–373 K
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71073 Å
a = 10.7519 (11) Å	Cell parameters from 637 reflections
b = 10.0159 (10) Å	θ = −14–14°
c = 11.8287 (12) Å	µ = 3.25 mm^−1
β = 98.426 (2)°	T = 298 K
V = 1260.1 (2) Å^3	Plate, colorless
Z = 4	0.6 × 0.1 × 0.04 mm

Data collection

Siemens SMART CCD PLATFORM diffractometer	2221 independent reflections
Radiation source: fine-focus sealed tube	1950 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.018
Detector resolution: 0 pixels mm^-1	θmax = 25.0°, θmin = 1.9°
ω scans	h = −12→12
Absorption correction: multi-scan (SADABS; Sheldrick, 2000)	k = −11→11
Tmin = 0.600, Tmax = 0.880	l = −14→13
9284 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.028	H-atom parameters constrained
wR(F^2) = 0.081	w = 1/[σ^2(Fo^2) + (0.0461P)^2 + 0.6983P] where P = (Fo^2 + 2Fc^2)/3
S = 1.00	(Δ/σ)max = 0.001
2221 reflections	Δρmax = 0.54 e Å^−3
150 parameters	Δρmin = −0.55 e Å^−3
0 restraints	Extinction correction: SHELXL, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0048 (9)

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.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
Br1	0.63640 (2)	1.08818 (3)	0.11983 (3)	0.06566 (15)
O1	0.27617 (18)	1.07684 (18)	0.46435 (16)	0.0588 (5)
O2	0.20183 (18)	0.8842 (2)	0.08330 (15)	0.0592 (5)
N1	0.16209 (17)	0.87311 (19)	0.18066 (16)	0.0397 (4)
C1	0.5214 (2)	1.0907 (2)	0.2277 (2)	0.0501 (6)
C2	0.5503 (3)	1.1622 (3)	0.3274 (3)	0.0592 (7)
H2	0.6241	1.2118	0.3409	0.071*
C3	0.4689 (3)	1.1596 (3)	0.4070 (3)	0.0597 (7)
H3	0.4877	1.2085	0.4742	0.072*
C4	0.3592 (2)	1.0853 (2)	0.3883 (2)	0.0484 (6)
C5	0.3288 (2)	1.0120 (2)	0.2859 (2)	0.0421 (5)
C6	0.4117 (2)	1.0173 (2)	0.2052 (2)	0.0455 (5)
H6	0.3929	0.9715	0.1364	0.055*
C7	0.3052 (3)	1.1467 (3)	0.5702 (2)	0.0667 (8)
H71	0.3852	1.1173	0.6090	0.100*
H72	0.2414	1.1290	0.6172	0.100*
H73	0.3085	1.2409	0.5557	0.100*
C8	0.2159 (2)	0.9307 (2)	0.2740 (2)	0.0420 (5)
H8	0.1783	0.9185	0.3392	0.050*
C9	0.0438 (2)	0.7883 (2)	0.17651 (19)	0.0413 (5)
C10	0.0712 (3)	0.6562 (3)	0.1223 (2)	0.0539 (6)
H101	0.1031	0.6726	0.0519	0.081*
H102	−0.0048	0.6048	0.1072	0.081*
H103	0.1326	0.6076	0.1734	0.081*
C11	−0.0599 (2)	0.8639 (3)	0.1020 (3)	0.0603 (7)
H111	−0.0713	0.9495	0.1356	0.090*
H112	−0.1368	0.8140	0.0962	0.090*
H113	−0.0371	0.8760	0.0272	0.090*
C12	0.0096 (3)	0.7633 (3)	0.2947 (2)	0.0548 (6)
H121	0.0803	0.7249	0.3427	0.082*
H122	−0.0604	0.7029	0.2891	0.082*
H123	−0.0127	0.8462	0.3271	0.082*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Br1	0.03918 (18)	0.0856 (3)	0.0715 (2)	−0.01188 (13)	0.00567 (13)	0.01389 (14)
O1	0.0474 (11)	0.0666 (12)	0.0622 (11)	−0.0067 (8)	0.0068 (9)	−0.0208 (9)
O2	0.0464 (10)	0.0871 (13)	0.0445 (10)	−0.0183 (9)	0.0076 (8)	0.0022 (9)
N1	0.0325 (10)	0.0430 (10)	0.0430 (10)	−0.0023 (8)	0.0036 (8)	0.0011 (8)
C1	0.0358 (13)	0.0470 (14)	0.0656 (16)	−0.0030 (10)	0.0013 (11)	0.0114 (11)
C2	0.0394 (14)	0.0499 (15)	0.085 (2)	−0.0124 (11)	−0.0010 (13)	−0.0011 (14)
C3	0.0487 (15)	0.0535 (15)	0.0732 (18)	−0.0087 (12)	−0.0039 (13)	−0.0147 (13)
C4	0.0385 (14)	0.0432 (13)	0.0612 (15)	0.0008 (10)	0.0001 (11)	−0.0041 (11)
C5	0.0350 (12)	0.0372 (11)	0.0522 (13)	0.0003 (9)	−0.0001 (10)	0.0014 (10)
C6	0.0374 (12)	0.0436 (12)	0.0531 (13)	−0.0015 (10)	−0.0013 (10)	0.0045 (10)
C7	0.0638 (19)	0.0736 (18)	0.0598 (17)	0.0012 (15)	−0.0007 (14)	−0.0184 (15)
C8	0.0354 (12)	0.0420 (12)	0.0482 (13)	−0.0031 (9)	0.0050 (10)	−0.0026 (10)
C9	0.0336 (11)	0.0404 (12)	0.0492 (12)	−0.0059 (9)	0.0038 (9)	−0.0009 (10)
C10	0.0563 (16)	0.0473 (14)	0.0578 (15)	−0.0035 (12)	0.0067 (12)	−0.0081 (12)
C11	0.0372 (14)	0.0570 (15)	0.0822 (19)	−0.0030 (12)	−0.0064 (13)	0.0019 (14)
C12	0.0503 (15)	0.0586 (15)	0.0585 (15)	−0.0161 (12)	0.0182 (12)	−0.0092 (12)

Geometric parameters (Å, º)

Br1—C1	1.903 (3)	C7—H71	0.9600
O1—C4	1.360 (3)	C7—H72	0.9600
O1—C7	1.429 (3)	C7—H73	0.9600
O2—N1	1.290 (3)	C8—H8	0.9300
N1—C8	1.304 (3)	C9—C12	1.517 (3)
N1—C9	1.525 (3)	C9—C10	1.518 (3)
C1—C2	1.376 (4)	C9—C11	1.518 (3)
C1—C6	1.382 (3)	C10—H101	0.9600
C2—C3	1.377 (4)	C10—H102	0.9600
C2—H2	0.9300	C10—H103	0.9600
C3—C4	1.384 (4)	C11—H111	0.9600
C3—H3	0.9300	C11—H112	0.9600
C4—C5	1.413 (3)	C11—H113	0.9600
C5—C6	1.399 (3)	C12—H121	0.9600
C5—C8	1.452 (3)	C12—H122	0.9600
C6—H6	0.9300	C12—H123	0.9600
C4—O1—C7	118.0 (2)	N1—C8—C5	126.3 (2)
O2—N1—C8	123.66 (19)	N1—C8—H8	116.9
O2—N1—C9	113.76 (17)	C5—C8—H8	116.9
C8—N1—C9	122.57 (19)	C12—C9—C10	109.5 (2)
C2—C1—C6	121.4 (3)	C12—C9—C11	111.1 (2)
C2—C1—Br1	119.61 (19)	C10—C9—C11	111.2 (2)
C6—C1—Br1	118.9 (2)	C12—C9—N1	112.07 (18)
C1—C2—C3	119.3 (2)	C10—C9—N1	106.65 (19)
C1—C2—H2	120.3	C11—C9—N1	106.18 (18)
C3—C2—H2	120.3	C9—C10—H101	109.5
C2—C3—C4	120.9 (3)	C9—C10—H102	109.5
C2—C3—H3	119.6	H101—C10—H102	109.5
C4—C3—H3	119.6	C9—C10—H103	109.5
O1—C4—C3	123.7 (2)	H101—C10—H103	109.5
O1—C4—C5	116.3 (2)	H102—C10—H103	109.5
C3—C4—C5	120.0 (2)	C9—C11—H111	109.5
C6—C5—C4	118.4 (2)	C9—C11—H112	109.5
C6—C5—C8	124.2 (2)	H111—C11—H112	109.5
C4—C5—C8	117.4 (2)	C9—C11—H113	109.5
C1—C6—C5	120.0 (2)	H111—C11—H113	109.5
C1—C6—H6	120.0	H112—C11—H113	109.5
C5—C6—H6	120.0	C9—C12—H121	109.5
O1—C7—H71	109.5	C9—C12—H122	109.5
O1—C7—H72	109.5	H121—C12—H122	109.5
H71—C7—H72	109.5	C9—C12—H123	109.5
O1—C7—H73	109.5	H121—C12—H123	109.5
H71—C7—H73	109.5	H122—C12—H123	109.5
H72—C7—H73	109.5