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The preparation and crystal structure of the title compound, C20H25NO2, are described. The N atom substituent of the nitro­ne function adopts a conformation which minimizes the 1,3-allyl­ic strain.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270101009477/sk1479sup1.cif
Contains datablock I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270101009477/sk1479Isup2.hkl
Contains datablock I

CCDC reference: 173373

Comment top

The use of nitrones as intermediates in organic synthesis has elicited a great deal of interest over the years (Breuer, 1982; Hamer & Macaluso, 1964). Nitrones undergo 1,3-dipolar cycloaddition reactions with alkenes or alkynes to yield isoxazolidines or isoxazolines, which are easily converted to the corresponding aminoalcohols by N—O bond reduction (Gothelf & Jorgensen, 1998). Two other interesting features of nitrones are their greater stability and greater electrophilicity compared to the corresponding imines. Due to these characteristics, it has been established that nitrones could be used as precursors for the preparation of hydroxylamines and amines through nucleophilic additions onto the CN bond (Enders & Reinhold, 1997; Bloch, 1998; Lombardo & Trombini, 2000). Nitrones are also well known as radical spin-trapping agents (Janzen et al., 1978), and their use as potential drugs, antioxidants (Thomas et al., 1994) or enzyme inhibitors (Lee & Kim, 1998) is currently under investigation. Although many nitrones are recorded in the Cambridge Structural Database (2000), very few of them are homochiral aldonitrones bearing a sterogenic center contiguous to the nitrogen atom (Huber et al., 1985; Baskaran et al., 1998; Dhavale et al., 1997). Such nitrones are of interest as potential precursors for the stereoselective synthesis of amine derivatives. Consequently, information regarding the favoured conformation of these homochiral species is needed to help predict and explain the diastereoselectivity of their reactions. In this paper, we describe the preparation of (1S)-(Z)—N-(3'-methylbut-1'-yliden)-2-benzyloxy-1-phenylethanamine N-oxide from (S)-(+)-phenylglycinol (Scheme 1), and its crystal structure analysis. \sch

X-ray analysis confirmed the Z stereochemistry, commonly observed for aldonitrones. It shows a dihedral angle of 11.16 (2)° between the (C5—N1—C6) and (N1—C6—H11) planes, the hydrogen atom of the nitrone function and the benzylic hydrogen being almost eclipsed. This particular conformation results in a minimization of the 1,3-allylic strain (Hoffmann, 1989). Indeed the H11—C5—N1—O1—C6—H10 frame is nearly planar with a mean deviation from the plane of 0.036 Å and a largest deviation for C6 of 0.073 Å. It can be reasonably expected for such a conformation to be adopted in an apolar solution and, consequently this information could be used to explain the stereoselectivity of nucleophilic additions and cyloadditions onto this nitrone. If we focus on the nitrone function, it is of interest to compare some structural features of the title compound with similar compounds found in the Cambridge Structural Database (2000). There are three bonds originating from the N atom: one to an O atom, another to a Csp2 and a last one to a Csp3 atom. In our case these distances are 1.303 (2), 1.278 (2), 1.486 (2) Å, respectively, compared to 1.309, 1.288, 1.490 Å (Huber et al., 1985), 1.308, 1.302, 1.492 Å (Baskaran et al., 1998) and 1.289 Å, 1.288, 1.496 Å (Dhavale et al., 1997). If we consider the H atom set on the Csp3 atom we can define a dihedral angle between the two planes defined by (Csp2—N-Csp3) and (N-Csp3—H). From the above results, we see that in our case the angle value is 11.16 (2)°. From the reported examples we obtain the following values 8.67° (Huber et al., 1985), 3.26° (Baskaran et al., 1998), 6.43° (Dhavale et al., 1997). Thus there is a correlation between the dihedral angle value and the Csp2—N length: the longer the Csp2—N bond, the smaller the dihedral angle value. This result could be useful when examining the stereoselective additions onto nitrones since facial selectivity should be closely related to the spatial arrangement of the chain set on the nitrogen atom.

Experimental top

(S)-(+)-Phenylglycinol was selectively O-benzylated using potassium hydride and benzylbromide in THF (Meyers et al., 1978) in a yield of 94%. The resultant amine was then oxidized by a three-step sequence involving the formation of an imine with p-anisaldehyde, oxidation to the corresponding oxaziridine with meta-choloroperoxybenzoic acid, and subsequent hydrolysis (Wovkulich & Uskovic, 1985) to yield O-benzylphenylglycinol N-hydroxylamine in an overall yield of 78%. The hydroxylamine was then reacted with isovaleraldehyde in the presence of magnesium sulfate as a dehydrating agent, to yield the title nitrone as a yellow oil in a non-optimized yield of 76% (Dondoni et al., 1994). The nitrone crystallized upon standing at 279 K and its X-ray structure was studied.

To a stirred solution of (S)—N-hydroxy-2-benzyloxy-1-phenylethanamine (2.46 g, 10.1 mmol) in dichloromethane (30 ml) placed under inert atmosphere, were added isovaleraldehyde (869 mg, 10.1 mmol) and anhydrous magnesium sulfate (50 g). The stirring was maintained during 12 h, after which the mixture was filtered over celite, and the filtrate concentrated under vacuum to yield the crude product. The latter was chromatographed on silica gel using a mixture of pentane/ethylacetate (1/1) as eluent to afford 2.37 g of the pure nitrone (76% yield). Mp: 321–322 K. 1H NMR (300 MHz, CDCl3): δ 0.92 (d, J = 6.0 Hz, 3H), 0.94 (d, J=6.0 Hz, 3H), 1.89 (m, 1H), 2.41 (m, 2H), 3.75 (dd, J = 4.9, 10.1 Hz, 1H), 4.48 (t, J = 10.1 Hz, 1H), 4.53 (d, J = 12.1 Hz, 1H), 4.68 (d, J = 12.1 Hz, 1H), 4.95 (dd, J = 4.9, 10.1 Hz, 1H), 6.85 (t, J = 6.0 Hz, 1H), 7.32 (m, 8H), 7.48 (m, 2H). 13C NMR (75 MHz, CDCl3): δ 22.4, 25.9, 35.3, 69.5, 73.5, 77.9, 127.6, 127.8, 128.3, 128.5, 128.8, 134.7–137.9, 138.9. Analysis calculated for C20H25NO2 (%): C 77.14, H 8.09, N 4.50%. Found: C 76.74, H 8.14, N 4.4%.

Refinement top

The absolute configuration of the reported structure was choosen on the basis of the originating (S)-(+)-phenylglycinol. The H atoms were geometrically placed and their B set to 1.2 of the B value of the carying atom.

Computing details top

Data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: CAD-4 Software; data reduction: TEXSAN (Molecular Structure Corporation, 1992-1997); program(s) used to solve structure: SIR92 (Altomare et al., 1993); program(s) used to refine structure: TEXSAN; software used to prepare material for publication: TEXSAN.

Figures top
[Figure 1] Fig. 1. ORTEPII (Johnson, 1976) molecular diagram of the title compound. Ellipsoids are shown at the 30% probability level.
(I) top
Crystal data top
C20H25NO2Dx = 1.153 Mg m3
Mr = 311.42Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121Cell parameters from 25 reflections
a = 5.639 (3) Åθ = 10.1–11.6°
b = 15.073 (8) ŵ = 0.07 mm1
c = 21.113 (7) ÅT = 293 K
V = 1794 (1) Å3Orthorhombic prism, yellowish
Z = 40.28 × 0.25 × 0.22 mm
F(000) = 672.00
Data collection top
CAD-4
diffractometer
Rint = 0.048
Radiation source: X-ray tubeθmax = 30.0°, θmin = 2.4°
Graphite monochromatorh = 77
ω–2θ scansk = 021
6039 measured reflectionsl = 029
2991 independent reflections2 standard reflections every 120 reflections
2072 reflections with I > 1.00σ(I) intensity decay: 4.0%
Refinement top
Refinement on F0 restraints
Least-squares matrix: full0 constraints
R[F2 > 2σ(F2)] = 0.056H-atom parameters not refined
wR(F2) = 0.040Weighting scheme based on measured s.u.'s w = 1/[σ2(Fo) + 0.00004|Fo|2]
S = 2.00(Δ/σ)max = 0.028
2072 reflectionsΔρmax = 0.21 e Å3
208 parametersΔρmin = 0.20 e Å3
Crystal data top
C20H25NO2V = 1794 (1) Å3
Mr = 311.42Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 5.639 (3) ŵ = 0.07 mm1
b = 15.073 (8) ÅT = 293 K
c = 21.113 (7) Å0.28 × 0.25 × 0.22 mm
Data collection top
CAD-4
diffractometer
Rint = 0.048
6039 measured reflections2 standard reflections every 120 reflections
2991 independent reflections intensity decay: 4.0%
2072 reflections with I > 1.00σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.0560 restraints
wR(F2) = 0.040H-atom parameters not refined
S = 2.00Δρmax = 0.21 e Å3
2072 reflectionsΔρmin = 0.20 e Å3
208 parameters
Special details top

Refinement. The decay correction has been applied. The H-atoms were not refined.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O(1)1.0157 (2)0.60201 (7)0.20594 (5)0.0570 (3)
O(2)0.8122 (3)0.63580 (6)0.35059 (5)0.0666 (4)
N(1)0.7906 (3)0.61086 (7)0.21842 (5)0.0440 (3)
C(1)0.3874 (4)0.7551 (2)0.0811 (1)0.1142 (8)
C(2)0.6813 (5)0.8761 (1)0.0883 (1)0.0930 (7)
C(3)0.5635 (4)0.7993 (1)0.12320 (7)0.0676 (5)
C(4)0.7509 (4)0.73471 (9)0.14632 (7)0.0542 (4)
C(5)0.6576 (3)0.66859 (9)0.19188 (7)0.0492 (4)
C(6)0.6908 (3)0.54645 (9)0.26453 (6)0.0461 (4)
C(7)0.8337 (4)0.54957 (9)0.32493 (7)0.0564 (5)
C(8)0.9369 (4)0.6459 (1)0.40886 (8)0.0710 (5)
C(9)0.8064 (4)0.6048 (1)0.46396 (7)0.0560 (4)
C(10)0.5951 (4)0.6405 (1)0.48294 (9)0.0752 (6)
C(11)0.4733 (4)0.6062 (2)0.5334 (1)0.0999 (7)
C(12)0.5608 (6)0.5342 (2)0.56471 (8)0.1023 (8)
C(13)0.7693 (6)0.4977 (1)0.54691 (9)0.0999 (7)
C(14)0.8929 (5)0.5336 (1)0.49556 (8)0.0725 (6)
C(15)0.6724 (3)0.45506 (9)0.23566 (6)0.0438 (4)
C(16)0.8541 (3)0.3939 (1)0.24039 (8)0.0516 (4)
C(17)0.8275 (3)0.3098 (1)0.21341 (7)0.0559 (4)
C(18)0.6257 (4)0.2882 (1)0.18187 (8)0.0608 (5)
C(19)0.4472 (4)0.3486 (1)0.17613 (8)0.0704 (6)
C(20)0.4688 (4)0.4323 (1)0.20305 (8)0.0611 (5)
H(1)0.46570.73270.04460.137*
H(2)0.31410.70760.10320.137*
H(3)0.27020.79690.06850.137*
H(4)0.76960.85380.05350.112*
H(5)0.56310.91580.07340.112*
H(6)0.78470.90660.11640.112*
H(7)0.48210.82250.15900.081*
H(8)0.87370.76740.16640.065*
H(9)0.81380.70410.11080.065*
H(10)0.49320.66910.20170.059*
H(11)0.53440.56540.27440.055*
H(12)0.99540.53710.31610.068*
H(13)0.77430.50710.35420.068*
H(14)1.08750.61810.40500.085*
H(15)0.95790.70740.41700.085*
H(16)0.53170.68990.46070.090*
H(17)0.32840.63260.54660.120*
H(18)0.47480.50960.59920.123*
H(19)0.83120.44800.56910.120*
H(20)1.03900.50780.48270.087*
H(21)0.99650.40890.26190.062*
H(22)0.95150.26740.21720.067*
H(23)0.60900.23080.16380.073*
H(24)0.30720.33340.15360.085*
H(25)0.34330.47390.19910.073*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O(1)0.0488 (6)0.0552 (5)0.0668 (6)0.0002 (7)0.0071 (6)0.0064 (6)
O(2)0.110 (1)0.0432 (4)0.0469 (5)0.0041 (8)0.0041 (8)0.0039 (4)
N(1)0.0554 (8)0.0378 (5)0.0389 (6)0.0010 (8)0.0024 (7)0.0014 (5)
C(1)0.072 (1)0.147 (2)0.124 (2)0.009 (2)0.024 (2)0.059 (2)
C(2)0.132 (2)0.0605 (9)0.086 (1)0.010 (1)0.002 (2)0.0256 (9)
C(3)0.088 (1)0.0623 (9)0.0528 (9)0.024 (1)0.008 (1)0.0163 (8)
C(4)0.070 (1)0.0458 (7)0.0471 (7)0.004 (1)0.0034 (9)0.0079 (7)
C(5)0.057 (1)0.0426 (6)0.0476 (7)0.0055 (9)0.0016 (9)0.0056 (6)
C(6)0.0519 (9)0.0438 (7)0.0425 (8)0.0076 (9)0.0103 (8)0.0057 (6)
C(7)0.080 (1)0.0449 (7)0.0439 (8)0.006 (1)0.0010 (9)0.0027 (6)
C(8)0.100 (1)0.0603 (8)0.0524 (9)0.014 (1)0.004 (1)0.0076 (8)
C(9)0.075 (1)0.0533 (7)0.0395 (8)0.000 (1)0.003 (1)0.0109 (7)
C(10)0.080 (1)0.081 (1)0.064 (1)0.006 (2)0.007 (1)0.006 (1)
C(11)0.086 (1)0.130 (2)0.083 (1)0.021 (2)0.022 (1)0.038 (1)
C(12)0.140 (2)0.110 (2)0.057 (1)0.049 (2)0.022 (1)0.008 (1)
C(13)0.159 (2)0.074 (1)0.067 (1)0.011 (2)0.022 (2)0.013 (1)
C(14)0.089 (2)0.0612 (9)0.067 (1)0.011 (1)0.004 (1)0.0010 (9)
C(15)0.0496 (9)0.0424 (6)0.0393 (7)0.0043 (8)0.0052 (8)0.0080 (6)
C(16)0.051 (1)0.0470 (7)0.0572 (8)0.004 (1)0.0030 (9)0.0032 (7)
C(17)0.061 (1)0.0478 (7)0.0585 (9)0.0065 (9)0.002 (1)0.0026 (8)
C(18)0.074 (1)0.0482 (7)0.0604 (9)0.010 (1)0.007 (1)0.0042 (7)
C(19)0.064 (1)0.072 (1)0.075 (1)0.018 (1)0.010 (1)0.007 (1)
C(20)0.047 (1)0.0614 (9)0.075 (1)0.003 (1)0.007 (1)0.0064 (9)
Geometric parameters (Å, º) top
O1—N11.303 (2)C1—H20.95
N1—C51.278 (2)C1—H30.95
N1—C61.486 (2)C2—H40.95
C4—C51.482 (2)C2—H50.95
C6—C71.509 (2)C2—H60.95
C6—C151.510 (2)C3—H70.95
O2—C71.413 (2)C4—H80.95
O2—C81.425 (2)C4—H90.95
C1—C31.491 (3)C5—H100.95
C2—C31.524 (3)C6—H110.95
C3—C41.518 (3)C7—H120.95
C8—C91.509 (2)C7—H130.95
C9—C101.367 (3)C8—H140.95
C9—C141.355 (2)C8—H150.95
C10—C111.369 (3)C10—H160.95
C11—C121.363 (3)C11—H170.95
C12—C131.351 (4)C12—H180.95
C13—C141.398 (3)C13—H190.95
C15—C161.382 (2)C14—H200.95
C15—C201.382 (2)C16—H210.95
C16—C171.398 (2)C17—H220.95
C17—C181.358 (3)C18—H230.95
C18—C191.363 (3)C19—H240.95
C19—C201.388 (2)C20—H250.95
C1—H10.95
O1—N1—C5123.6 (1)C2—C3—H7108.4
O1—N1—C6115.8 (1)C4—C3—H7108.4
C5—N1—C6120.6 (1)C3—C4—H8108.5
N1—C5—C4122.3 (2)C3—C4—H9108.5
N1—C6—C7109.3 (1)C5—C4—H8108.5
N1—C6—C15111.0 (1)C5—C4—H9108.5
C7—C6—C15114.0 (1)H8—C4—H9109.5
C7—O2—C8112.7 (1)N1—C5—H10118.9
C1—C3—C2110.0 (2)C4—C5—H10118.9
C1—C3—C4111.6 (2)N1—C6—H11107.4
C2—C3—C4109.8 (2)C7—C6—H11107.5
C3—C4—C5113.2 (2)C15—C6—H11107.4
O2—C7—C6107.9 (1)O2—C7—H12109.9
O2—C8—C9112.4 (2)O2—C7—H13109.9
C8—C9—C10119.3 (2)C6—C7—H12109.9
C8—C9—C14121.9 (2)C6—C7—H13109.9
C10—C9—C14118.8 (2)H12—C7—H13109.5
C9—C10—C11121.1 (2)O2—C8—H14108.7
C10—C11—C12119.7 (2)O2—C8—H15108.7
C11—C12—C13120.3 (2)C9—C8—H14108.7
C12—C13—C14119.5 (2)C9—C8—H15108.8
C9—C14—C13120.6 (2)H14—C8—H15109.5
C6—C15—C16121.9 (1)C9—C10—H16119.4
C6—C15—C20119.0 (1)C11—C10—H16119.4
C16—C15—C20119.1 (1)C10—C11—H17120.1
C15—C16—C17119.8 (2)C12—C11—H17120.2
C16—C17—C18120.5 (2)C11—C12—H18119.8
C17—C18—C19120.1 (1)C13—C12—H18119.9
C18—C19—C20120.4 (2)C12—C13—H19120.2
C15—C20—C19120.2 (2)C14—C13—H19120.3
C3—C1—H1109.5C9—C14—H20119.7
C3—C1—H2109.5C13—C14—H20119.7
C3—C1—H3109.5C15—C16—H21120.1
H1—C1—H2109.5C17—C16—H21120.1
H1—C1—H3109.5C16—C17—H22119.8
H2—C1—H3109.5C18—C17—H22119.8
C3—C2—H4109.5C17—C18—H23120.0
C3—C2—H5109.5C19—C18—H23119.9
C3—C2—H6109.5C18—C19—H24119.8
H4—C2—H5109.5C20—C19—H24119.8
H4—C2—H6109.5C15—C20—H25119.9
H5—C2—H6109.5C19—C20—H25119.9
C1—C3—H7108.4

Experimental details

Crystal data
Chemical formulaC20H25NO2
Mr311.42
Crystal system, space groupOrthorhombic, P212121
Temperature (K)293
a, b, c (Å)5.639 (3), 15.073 (8), 21.113 (7)
V3)1794 (1)
Z4
Radiation typeMo Kα
µ (mm1)0.07
Crystal size (mm)0.28 × 0.25 × 0.22
Data collection
DiffractometerCAD-4
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 1.00σ(I)] reflections
6039, 2991, 2072
Rint0.048
(sin θ/λ)max1)0.703
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.056, 0.040, 2.00
No. of reflections2072
No. of parameters208
H-atom treatmentH-atom parameters not refined
Δρmax, Δρmin (e Å3)0.21, 0.20

Computer programs: CAD-4 Software (Enraf-Nonius, 1989), CAD-4 Software, TEXSAN (Molecular Structure Corporation, 1992-1997), SIR92 (Altomare et al., 1993), TEXSAN.

Selected geometric parameters (Å, º) top
O1—N11.303 (2)C4—C51.482 (2)
N1—C51.278 (2)C6—C71.509 (2)
N1—C61.486 (2)C6—C151.510 (2)
O1—N1—C5123.6 (1)N1—C6—C7109.3 (1)
O1—N1—C6115.8 (1)N1—C6—C15111.0 (1)
C5—N1—C6120.6 (1)C7—C6—C15114.0 (1)
N1—C5—C4122.3 (2)
 

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