(1S)-(Z)-2-benzyloxy-N-(3-methyl-1-butylidene)-1-phenylethylamine N-oxide

Article abstract of DOI:10.1107/S0108270101009477

The preparation and crystal structure of (1S)-(Z)-2-benyloxy-N-(3-methyl-1-butylidene)-1-phenylethylamine N-oxide was described. A dihedral angle of 11.16 (2)° was observed between the C5/N1/C6 and N1/C6/H11 planes. There were three bonds originating from the N atom, to an oxygen atom, to a Csp² and to a Csp³ atom. The nitrogen atom substituent of the nitrone function adopted a conformation which minimizes the 1,3-allylic strain.

Full text of DOI:10.1107/S0108270101009477

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
nitrones bearing a stereogenic center contiguous to the N
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. Conse-
quently, 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)-2-benzyloxy-N-(3-
methyl-1-butylidene)-1-phenylethylamine N-oxide, (I), from
(S)-(+)-phenylglycinol and its crystal structure analysis.
X-ray analysis con®rmed the Z stereochemistry, commonly
observed for aldonitrones. A dihedral angle of 11.16 (2)ꢀ is
observed between the C5/N1/C6 and N1/C6/H11 planes; the H
atom of the nitrone function and the benzylic H atom being
almost eclipsed. This particular conformation results in a
minimization of the 1,3-allylic strain (Hoffmann, 1989).
Indeed, the H11ÐC5ÐN1ÐO1ÐC6ÐH10 frame is nearly
ISSN 0108-2701
(1S)-(Z)-2-Benzyloxy-N-(3-methyl-
1-butylidene)-1-phenylethylamine
N-oxide
 Á
David Drouard, Sandrine Py, Marie-Therese Averbuch,
Â
Christian Philouze and Yannick Vallee*
Â
LEDSS, UMR CNRS 5616, Universite Joseph Fourier, BP 53, 38041 Grenoble
CEDEX 9, France
Correspondence e-mail: yannick.vallee@ujf-grenoble.fr
Ê
planar, with a mean deviation from the plane of 0.036 A and a
Received 18 April 2001
Accepted 6 June 2001
Ê
largest deviation for C6 of 0.073 A. 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
cycloadditions 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
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.
Comment
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 NÐO bond reduction
(Gothelf & Jorgensen, 1998). Two other interesting features of
nitrones are their greater stability and greater electrophilicity
compared with the corresponding imines. Due to these char-
acteristics, it has been established that nitrones could be used
Ê
are 1.303 (2), 1.278 (2) and 1.486 (2) A, respectively,
compared to respective values in other structures of 1.309,
Ê
1.288 and 1.490 A (Huber et al., 1985), 1.308, 1.302 and
Ê
Ê
1.492 A (Baskaran et al., 1998), and 1.289, 1.288 and 1.496 A
(Dhavale et al., 1997). If we consider the H atom set on the
Csp3 atom, we can de®ne a dihedral angle between the two
planes de®ned 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:
as precursors for the preparation of hydroxylamines and
amines through nucleophilic additions onto the C N bond
(Enders & Reinhold, 1997; Bloch, 1998; Lombardo & Trom-
bini, 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) and enzyme inhibi-
tors (Lee & Kim, 1998) is currently under investigation.
Although many nitrones are recorded in the Cambridge
Structural Database (2000), very few are homochiral aldo-
Figure 1
ORTEPII (Johnson, 1976) molecular diagram of the title compound.
Ellipsoids are shown at the 30% probability level.
ꢁ
Acta Cryst. (2001). C57, 1079±1080
# 2001 International Union of Crystallography
Printed in Great Britain ± all rights reserved 1079

organic compounds
8.67 (Huber et al., 1985), 3.26 (Baskaran et al., 1998) and 6.43ꢀ
(Dhavale et al., 1997). Thus, there is a correlation between the
dihedral angle value and the Csp2ÐN length, i.e. the longer
the Csp2ÐN bond, the smaller the dihedral angle. This result
could be useful when examining stereoselective additions onto
nitrones, since facial selectivity should be closely related to the
spatial arrangement of the chain set on the N atom.
Data collection
Enraf±Nonius CAD-4 diffrac-
tometer
!±2ꢂ scans
6039 measured re¯ections
2991 independent re¯ections
2072 re¯ections with I > ꢄ(I)
Rint = 0.048
ꢂmax = 30.0ꢀ
h = 7 ! 7
k = 0 ! 21
l = 0 ! 29
2 standard re¯ections
every 120 re¯ections
intensity decay: 4.0%
Re®nement
Re®nement on F
R = 0.056
wR = 0.040
S = 2.00
2072 re¯ections
208 parameters
H-atom parameters not re®ned
w = 1/[ꢄ2(Fo) + 0.00004|Fo|2]
(Á/ꢄ)max = 0.028
Experimental
(S)-(+)-Phenylglycinol was selectively O-benzylated using potassium
hydride and benzyl bromide in tetrahydrofuran (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-anis-
aldehyde, oxidation to the corresponding oxaziridine with meta-
chloroperoxybenzoic acid, and subsequent hydrolysis (Wovkulich &
Uskokovic, 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 dehy-
drating agent (Dondoni et al., 1994), to yield the title nitrone as a
yellow oil in a non-optimized yield of 76%, according to the following
procedure: to a stirred solution of (S)-N-hydroxy-2-benzyloxy-1-
phenylethanamine (2.46 g, 10.1 mmol) in dichloromethane (30 ml)
placed under an inert atmosphere were added isovaleraldehyde
(869 mg, 10.1 mmol) and anhydrous magnesium sulfate (50 g). Stir-
ring was continued for a period of 12 h, after which the mixture was
®ltered over celite and the ®ltrate concentrated under vacuum to
yield the crude product. The latter was chromatographed on silica gel
using a mixture of pentane/ethyl acetate (1:1) as eluent to afford
2.37 g of the pure nitrone which crystallized upon standing at 279 K
(m.p. 321±322 K). 1H NMR (300 MHz, CDCl3, p.p.m.): ꢀ 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, p.p.m.): ꢀ 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 p.p.m.; analysis calculated for
C20H25NO2: C 77.14, H 8.09, N 4.50%; found: C 76.74, H 8.14, N 4.4%.
3
Ê
Áꢅmax = 0.21 e A
3
Ê
0.20 e A
Áꢅmin
=
The absolute con®guration of the reported structure was chosen
on the basis of the originating (S)-(+)-phenylglycinol. The H atoms
were placed geometrically and their Uiso values set to 1.2 of the Ueq
value of the parent atom.
Data collection: CAD-4 Software (Enraf±Nonius, 1989); cell
re®nement: CAD-4 Software; data reduction: TEXSAN (Molecular
Structure Corporation, 1992±1997); program(s) used to solve struc-
ture: SIR92 (Altomare et al., 1993); program(s) used to re®ne struc-
ture: TEXSAN; software used to prepare material for publication:
TEXSAN.
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: SK1479). Services for accessing these data are
described at the back of the journal.
References
Altomare, A. M., Cascarano, G., Giacovazzo, C. & Guagliardi, A. (1993). J.
Appl. Cryst. 26, 343±350.
Baskaran, S., Aurich, H. G., Biesmeier, F. & Harms, K. (1998). Tetrahedron, 54,
12249±12264.
Bloch, R. (1998). Chem. Rev. 98, 1407±1438.
Breuer, E. (1982). The Chemistry of Amino, Nitroso and Nitro Compounds,
and their Derivatives, edited by S. Patai, Part 1, ch. 13. New York: Wiley.
Cambridge Structural Database (2000). Version 2.3.8. Cambridge Crystallo-
graphic Data Centre, 12 Union Road, Cambridge, England.
Dhavale, D. D., Desai, V. N., Sindkhedkar, M. D., Mali, R. S., Castellari, C. &
Trombini, C. (1997). Tetrahedron Asymmetry, 8, 1475±1486.
Dondoni, A., Franco, S., Junquera, F., Merchan, F. L., Merino, P. & Tejero, T.
(1994). Synth. Commun. 24, 2537±2750.
Enders, D. & Reinhold, U. (1997). Tetrahedron Asymmetry, 8, 1895±1946.
Enraf±Nonius (1989). CAD-4 Software. Version 5.0. Enraf±Nonius, Delft, The
Netherlands.
Gothelf, K. V. & Jorgensen, K. A. (1998). Chem. Rev. 98, 863±909.
Hamer, J. & Macaluso, A. (1964). Chem. Rev. 64, pp. 473±495.
Hoffmann, R. W. (1989). Chem. Rev. 89, 1841±1861.
Crystal data
C20H25NO2
Mr = 311.42
Mo Kꢁ radiation
Cell parameters from 25
re¯ections
Orthorhombic, P212121
Ê
a = 5.639 (3) A
ꢂ = 10.1±11.6ꢀ
1
Ê
b = 15.073 (8) A
ꢃ = 0.07 mm
T = 293 K
Ê
c = 21.113 (7) A
3
Ê
V = 1794 (1) A
Orthorhombic prism, yellow
0.28 Â 0.25 Â 0.22 mm
Z = 4
Dx = 1.153 Mg m
3
Huber, R., Knierzinger, A., Obrecht, J.-P. & Vasella, A. (1985). Helv. Chim.
Acta, 68, 1730±1747.
Janzen, E. G., Evans, C. A. & Davis, E. R. (1978). In Organic Free Radicals;
Am. Chem. Soc. Symp. Ser., edited by W. A. Prior, Vol. 69, pp. 433±446.
Washington, DC: American Chemical Society.
Table 1
Selected geometric parameters (A, ).
ꢀ
Ê
Johnson, C. K. (1976). ORTEPII. Report ORNL-5138. Oak Ridge National
Laboratory, Tennessee, USA.
O1ÐN1
N1ÐC5
N1ÐC6
1.303 (2)
1.278 (2)
1.486 (2)
C4ÐC5
C6ÐC7
C6ÐC15
1.482 (2)
1.509 (2)
1.510 (2)
Lee, K. J. & Kim, D. H. (1998). Bioorg. Med. Chem. Lett. 8, 323±326.
Lombardo, M. & Trombini, C. (2000). Synthesis, 6, 759±774.
Meyers, A. I., Poindexter, G. S. & Brich, Z. (1978). J. Org. Chem. 43, 872±898.
Molecular Structure Corporation (1992±1997). TEXSAN. Version 1.7. MSC,
3200 Research Forest Drive, The Woodlands, TX 77381, USA.
Thomas, C. E., Carney, J. M., Bernotas, R. C., Hay, D. A. & Carr, A. A. (1994).
Ann. NY Acad. Sci. 234, 243±249.
O1ÐN1ÐC5
O1ÐN1ÐC6
C5ÐN1ÐC6
N1ÐC5ÐC4
123.6 (1)
115.8 (1)
120.6 (1)
122.3 (2)
N1ÐC6ÐC7
N1ÐC6ÐC15
C7ÐC6ÐC15
109.3 (1)
111.0 (1)
114.0 (1)
Wovkulich, P. M. & Uskokovic, M. R. (1985). Tetrahedron, 41, 3455±3462.
ꢁ
1080 David Drouard et al.
C20H25NO2
Acta Cryst. (2001). C57, 1079±1080