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Acta Cryst. (2011). E67, o1116-o1117    [ doi:10.1107/S1600536811013055 ]

(3R,4S)-3,4-Isopropylidenedioxy-3,4-dihydro-2H-pyrrole 1-oxide

M. F. Flores, P. Garcia, N. M. Garrido, F. Sanz and D. Diez

Abstract top

The title compound C7H11NO3 was prepared by intramolecular nucleophilic displacement of 2,3-O-iso-propylidene-D-erythronolactol. There are two molecules in the asymmetric unit, which are related by a pseudo-inversion centre. The crystal structure determination confirms unequivocally the configuration of the chiral centres as 3S,4R. In the crystal structure, intermolecular C-H...O interactions link the molecules (into infinite zigzag chains along the a axis.

Comment top

Nitrones have been the subject of intense research efforts, because of the wide role played in the synthesis of complex molecular frameworks. They undergo several synthetically useful reactions such as 1,3-dipolar cycloadditions, (Tufariello et al., 1984) nucleophilic additions, (Merino et al., 2000; Lombardo et al., 2002). Both the reactions give rise to the formation of new carbon-carbon bonds, often with a high degree of stereocontrol. These features, together with the direct access to nitrones by simple reactions (Hamer et al., 1964; Döpp et al., 1990), and their stability which permits isolation and long storage, make nitrones ideal tools for application in organic syntheses, particularly in the field of alkaloids, nitrogen containing natural products or bioactive analogues. The construction of highly functionalized nitrogen heterocycles in a stereoselective manner is an important focus of medicinal and natural product chemistry. Although, in the last few years, the title compound has been reported more and more in the literature as a starting material due to its biological relevance in the synthesis of polyhydroxypyrrolidines or polyhydroxypyrrolizidines, both interesting compounds as potential glycosidase inhibitors and consequently as potential therapeutic (antibiotic, antiviral, antitumoral) agents (Hall et al., 1997; Closa et al., 1998; McCaig et al., 1998; Cicchi et al., 2002; Revuelta et al., 2007) there was not any crystallographic data.

Following our special interest in nitrogen compounds such as isoxazolidines, we prepared the title N-oxide, and its crystal structure is reported here.

The asymmetric unit contains two symmetrically independent molecules. The title molecule consists of a pyrroline-N-oxide ring with an isopropylidenedioxy as substituent. All the bond lengths and angles are within the normal ranges. The carbonyl group at N1 is coplanar with the pyrroline ring being the O3—N1=C3—C4 and O3'-N1'=C3'-C4' torsion angles of 179.1 (4)° and 179.2 (7)°, respectively. These results are in good agreement with the literature (Keleşoğlu et al., 2010).

In the crystal structure, intermolecular C—H···O interactions (Table 1) link the molecules (Fig. 2) into infinite zigzag chains along the a axis.

Related literature top

Nitrones play a useful role in the synthesis of complex molecular frameworks, undergoing several synthetically useful reactions such as 1,3-dipolar cycloadditions (Tufariello, 1984) and nucleophilic addition (Merino et al., 2000; Lombardo & Trombini, 2002). They also allow direct access to nitrones by simple reactions, see: Döpp & Döpp (1990); Hamer & Macaluso (1964). For the use of the title compound as a starting material in the sythesis of potential therapeutic (antibiotic, antiviral, antitumoral) agents, see: Hall et al. (1997); Closa & Wightman (1998); McCaig et al. (1998); Cicchi et al. (2002); Revuelta et al. (2007). For a related structure, see: Keleşoğlu et al. (2010). For the preparation of the title compound, see: Flores et al. (2010); Cicchi et al. (2006).

Experimental top

The title N-oxide was obtained by intramolecular nucleophilic displacement, which is based on a simple one-pot procedure employing NH2OSiMe2t-Bu, methanesulfonyl chloride, and 2,3-O-iso-propylidene-D-erythronolactol, according to the methodology described by Cicchi et al. (2006) and by us (Flores et al., 2010). Well shaped colourless single crystals were obtained by crystallization from CH2Cl2/MeOH.

Refinement top

Hydrogen atoms were positioned geometrically, with C—H distances constrained to 0.93 Å (aromatic CH), 0.96 Å (methyl), 0.97 Å (methylene) and 0.98 Å (methine) and refined in riding mode with Uiso(H) = xUeq(C), where x = 1.5 for methyl H atoms and x = 1.2 for all other atoms.

Computing details top

Data collection: APEX2 (Bruker, 2006); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT (Bruker, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Mercury (Macrae et al., 2006); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. Molecular structure of C7H11NO3.
[Figure 2] Fig. 2. Crystal packing of C7H11NO3 view along b axis, showing intermolecular hydrogen bonding.
(3R,4S)-3,4-Isopropylidenedioxy-3,4-dihydro-2H-pyrrole 1-oxide top
Crystal data top
C7H11NO3F(000) = 672
Mr = 157.17Dx = 1.302 Mg m−3
Monoclinic, C2Cu Kα radiation, λ = 1.54178 Å
Hall symbol: C 2yCell parameters from 2365 reflections
a = 11.335 (2) Åθ = 1.7–66.9°
b = 5.4467 (11) ŵ = 0.86 mm−1
c = 26.508 (5) ÅT = 298 K
β = 101.40 (3)°Prismatic, colourless
V = 1604.2 (6) Å30.15 × 0.10 × 0.08 mm
Z = 8
Data collection top
Bruker APEXII CCD area-detector
diffractometer		2365 independent reflections
Radiation source: fine-focus sealed tube2261 reflections with I > 2σ(I)
graphiteRint = 0.022
phi and ω scansθmax = 66.9°, θmin = 1.7°
Absorption correction: multi-scan
(SADABS; Bruker, 2006)		h = −13→11
Tmin = 0.902, Tmax = 0.934k = −6→5
4369 measured reflectionsl = −28→31
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.033 w = 1/[σ2(Fo2) + (0.0479P)2 + 0.4187P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.091(Δ/σ)max = 0.001
S = 1.05Δρmax = 0.16 e Å−3
2365 reflectionsΔρmin = −0.11 e Å−3
204 parametersExtinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraintExtinction coefficient: 0.00105 (18)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack (1983), 761 Friedel pairs
Secondary atom site location: difference Fourier mapFlack parameter: 0.0 (2)
Crystal data top
C7H11NO3V = 1604.2 (6) Å3
Mr = 157.17Z = 8
Monoclinic, C2Cu Kα radiation
a = 11.335 (2) ŵ = 0.86 mm−1
b = 5.4467 (11) ÅT = 298 K
c = 26.508 (5) Å0.15 × 0.10 × 0.08 mm
β = 101.40 (3)°
Data collection top
Bruker APEXII CCD area-detector
diffractometer		2365 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2006)		2261 reflections with I > 2σ(I)
Tmin = 0.902, Tmax = 0.934Rint = 0.022
4369 measured reflectionsθmax = 66.9°
Refinement top
R[F2 > 2σ(F2)] = 0.033H-atom parameters constrained
wR(F2) = 0.091Δρmax = 0.16 e Å−3
S = 1.05Δρmin = −0.11 e Å−3
2365 reflectionsAbsolute structure: Flack (1983), 761 Friedel pairs
204 parametersFlack parameter: 0.0 (2)
1 restraint
Special details top

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 (Å2) top
xyzUiso*/Ueq
O1'0.30975 (12)0.5460 (3)0.84350 (5)0.0571 (4)
O2'0.44334 (11)0.8279 (3)0.88116 (5)0.0566 (4)
O3'0.14788 (12)0.7976 (4)0.96810 (6)0.0693 (5)
N1'0.23631 (12)0.7223 (3)0.94785 (5)0.0481 (4)
C1'0.33483 (16)0.4762 (4)0.89604 (7)0.0476 (4)
H1'0.37290.31420.90130.057*
C3'0.34095 (15)0.8196 (4)0.95186 (6)0.0464 (4)
H3'0.36570.96010.97090.056*
C4'0.41764 (14)0.6811 (4)0.92243 (6)0.0463 (4)
H4'0.49070.61680.94450.056*
C5'0.40764 (17)0.6940 (4)0.83486 (7)0.0525 (5)
C6'0.3627 (3)0.8714 (6)0.79227 (9)0.0866 (8)
H6'10.29850.96740.80090.130*
H6'20.33370.78260.76100.130*
H6'30.42710.97800.78760.130*
C7'0.5109 (3)0.5377 (6)0.82529 (12)0.0928 (9)
H7'10.48600.44580.79410.139*
H7'20.53490.42660.85360.139*
H7'30.57760.64130.82210.139*
C2'0.22244 (16)0.4919 (4)0.91839 (8)0.0553 (5)
H2'10.15100.49650.89130.066*
H2'20.21680.35280.94060.066*
O10.09613 (11)0.3663 (3)0.62016 (5)0.0557 (4)
O20.21761 (13)0.6589 (3)0.66182 (5)0.0666 (5)
O30.36792 (14)0.3733 (4)0.52993 (7)0.0861 (6)
N10.29356 (13)0.4731 (4)0.55436 (6)0.0544 (4)
C10.10961 (15)0.5348 (4)0.58059 (7)0.0514 (5)
H10.03410.61860.56590.062*
C20.16439 (16)0.4088 (4)0.54033 (7)0.0556 (5)
H2A0.15300.23250.54130.067*
H2B0.12930.46870.50620.067*
C30.31507 (17)0.6385 (4)0.58935 (8)0.0586 (5)
H30.39100.70490.60140.070*
C40.20620 (17)0.7127 (4)0.60855 (7)0.0522 (5)
H40.18470.88480.60070.063*
C50.12362 (18)0.4967 (4)0.66756 (7)0.0558 (5)
C60.0151 (3)0.6365 (7)0.67681 (11)0.0971 (10)
H6A−0.04640.52280.68160.146*
H6B−0.01480.73940.64770.146*
H6C0.03740.73650.70700.146*
C70.1714 (3)0.3142 (6)0.70956 (9)0.0882 (8)
H7A0.24040.23200.70160.132*
H7B0.11010.19580.71200.132*
H7C0.19420.39900.74180.132*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O1'0.0642 (8)0.0626 (10)0.0440 (7)−0.0248 (7)0.0098 (6)−0.0060 (6)
O2'0.0573 (7)0.0637 (9)0.0517 (7)−0.0225 (7)0.0178 (6)−0.0098 (7)
O3'0.0556 (7)0.0876 (12)0.0713 (9)0.0236 (8)0.0283 (7)0.0071 (9)
N1'0.0431 (7)0.0554 (10)0.0467 (8)0.0091 (7)0.0108 (6)0.0067 (7)
C1'0.0541 (9)0.0433 (10)0.0471 (9)0.0010 (9)0.0142 (8)0.0032 (8)
C3'0.0484 (9)0.0476 (10)0.0420 (9)−0.0002 (8)0.0061 (7)0.0000 (8)
C4'0.0374 (8)0.0565 (12)0.0434 (9)0.0022 (8)0.0042 (7)0.0000 (9)
C5'0.0612 (11)0.0527 (12)0.0467 (10)−0.0157 (9)0.0176 (8)−0.0056 (9)
C6'0.115 (2)0.0827 (19)0.0616 (13)−0.0206 (17)0.0163 (13)0.0152 (14)
C7'0.1036 (19)0.084 (2)0.108 (2)0.0040 (17)0.0634 (17)−0.0118 (18)
C2'0.0509 (10)0.0578 (12)0.0581 (11)−0.0114 (10)0.0127 (8)−0.0032 (10)
O10.0564 (7)0.0588 (9)0.0530 (7)−0.0180 (7)0.0137 (6)−0.0052 (7)
O20.0758 (9)0.0742 (12)0.0499 (8)−0.0306 (9)0.0126 (6)−0.0074 (8)
O30.0679 (9)0.1030 (15)0.0940 (11)0.0252 (10)0.0316 (8)−0.0034 (12)
N10.0472 (8)0.0598 (10)0.0560 (9)0.0068 (8)0.0098 (7)0.0045 (9)
C10.0395 (8)0.0617 (14)0.0502 (10)0.0022 (9)0.0022 (7)0.0044 (9)
C20.0511 (10)0.0646 (14)0.0488 (10)−0.0048 (9)0.0045 (8)−0.0025 (10)
C30.0465 (9)0.0662 (14)0.0612 (11)−0.0129 (9)0.0061 (8)0.0058 (11)
C40.0600 (11)0.0397 (10)0.0572 (11)−0.0048 (9)0.0127 (9)0.0008 (9)
C50.0627 (11)0.0549 (12)0.0523 (10)−0.0128 (10)0.0179 (8)−0.0059 (10)
C60.0920 (19)0.112 (3)0.098 (2)0.0096 (19)0.0441 (16)−0.018 (2)
C70.127 (2)0.0758 (18)0.0603 (13)−0.0100 (18)0.0159 (13)0.0090 (14)
Geometric parameters (Å, °) top
O1'—C1'1.417 (2)O1—C51.423 (2)
O1'—C5'1.426 (2)O1—C11.425 (2)
O2'—C5'1.416 (2)O2—C51.415 (2)
O2'—C4'1.431 (2)O2—C41.423 (2)
O3'—N1'1.2937 (19)O3—N11.281 (2)
N1'—C3'1.284 (2)N1—C31.282 (3)
N1'—C2'1.470 (3)N1—C21.480 (2)
C1'—C2'1.510 (2)C1—C21.502 (3)
C1'—C4'1.535 (3)C1—C41.538 (3)
C1'—H1'0.9800C1—H10.9800
C3'—C4'1.484 (3)C2—H2A0.9700
C3'—H3'0.9300C2—H2B0.9700
C4'—H4'0.9800C3—C41.481 (3)
C5'—C6'1.497 (3)C3—H30.9300
C5'—C7'1.509 (4)C4—H40.9800
C6'—H6'10.9600C5—C61.507 (3)
C6'—H6'20.9600C5—C71.511 (4)
C6'—H6'30.9600C6—H6A0.9600
C7'—H7'10.9600C6—H6B0.9600
C7'—H7'20.9600C6—H6C0.9600
C7'—H7'30.9600C7—H7A0.9600
C2'—H2'10.9700C7—H7B0.9600
C2'—H2'20.9700C7—H7C0.9600
C1'—O1'—C5'107.35 (14)C5—O1—C1106.97 (16)
C5'—O2'—C4'107.96 (15)C5—O2—C4108.22 (15)
C3'—N1'—O3'127.85 (19)O3—N1—C3127.89 (18)
C3'—N1'—C2'113.34 (15)O3—N1—C2119.33 (19)
O3'—N1'—C2'118.74 (16)C3—N1—C2112.67 (16)
O1'—C1'—C2'110.46 (15)O1—C1—C2110.37 (18)
O1'—C1'—C4'103.80 (15)O1—C1—C4102.75 (14)
C2'—C1'—C4'105.50 (15)C2—C1—C4105.98 (15)
O1'—C1'—H1'112.2O1—C1—H1112.4
C2'—C1'—H1'112.2C2—C1—H1112.4
C4'—C1'—H1'112.2C4—C1—H1112.4
N1'—C3'—C4'111.98 (18)N1—C2—C1103.94 (16)
N1'—C3'—H3'124.0N1—C2—H2A111.0
C4'—C3'—H3'124.0C1—C2—H2A111.0
O2'—C4'—C3'110.31 (17)N1—C2—H2B111.0
O2'—C4'—C1'104.86 (13)C1—C2—H2B111.0
C3'—C4'—C1'103.90 (14)H2A—C2—H2B109.0
O2'—C4'—H4'112.4N1—C3—C4112.86 (17)
C3'—C4'—H4'112.4N1—C3—H3123.6
C1'—C4'—H4'112.4C4—C3—H3123.6
O2'—C5'—O1'104.48 (13)O2—C4—C3111.49 (17)
O2'—C5'—C6'108.5 (2)O2—C4—C1105.37 (15)
O1'—C5'—C6'109.05 (19)C3—C4—C1102.97 (17)
O2'—C5'—C7'109.8 (2)O2—C4—H4112.2
O1'—C5'—C7'111.2 (2)C3—C4—H4112.2
C6'—C5'—C7'113.4 (2)C1—C4—H4112.2
C5'—C6'—H6'1109.5O2—C5—O1104.75 (13)
C5'—C6'—H6'2109.5O2—C5—C6111.0 (2)
H6'1—C6'—H6'2109.5O1—C5—C6110.64 (19)
C5'—C6'—H6'3109.5O2—C5—C7108.8 (2)
H6'1—C6'—H6'3109.5O1—C5—C7107.8 (2)
H6'2—C6'—H6'3109.5C6—C5—C7113.4 (2)
C5'—C7'—H7'1109.5C5—C6—H6A109.5
C5'—C7'—H7'2109.5C5—C6—H6B109.5
H7'1—C7'—H7'2109.5H6A—C6—H6B109.5
C5'—C7'—H7'3109.5C5—C6—H6C109.5
H7'1—C7'—H7'3109.5H6A—C6—H6C109.5
H7'2—C7'—H7'3109.5H6B—C6—H6C109.5
N1'—C2'—C1'104.30 (16)C5—C7—H7A109.5
N1'—C2'—H2'1110.9C5—C7—H7B109.5
C1'—C2'—H2'1110.9H7A—C7—H7B109.5
N1'—C2'—H2'2110.9C5—C7—H7C109.5
C1'—C2'—H2'2110.9H7A—C7—H7C109.5
H2'1—C2'—H2'2108.9H7B—C7—H7C109.5
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C3—H3···O1i0.932.443.366 (3)171
C1—H1···O3ii0.982.383.355 (3)171
C2—H2A···O3iii0.972.703.441 (3)134
C2—H2B···O3iv0.972.413.120 (3)130
C2'—H2'1···O2'v0.972.493.247 (2)135
C4'—H4'···O3'vi0.982.483.375 (3)152
C2'—H2'2···O3'vii0.972.613.254 (2)124
C3'—H3'···O3'viii0.932.483.345 (3)156
Symmetry codes: (i) x+1/2, y+1/2, z; (ii) x−1/2, y+1/2, z; (iii) −x+1/2, y−1/2, −z+1; (iv) −x+1/2, y+1/2, −z+1; (v) x−1/2, y−1/2, z; (vi) x+1/2, y−1/2, z; (vii) −x+1/2, y−1/2, −z+2; (viii) −x+1/2, y+1/2, −z+2.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C3—H3···O1i0.932.443.366 (3)171
C1—H1···O3ii0.982.383.355 (3)171
C2—H2A···O3iii0.972.703.441 (3)134
C2—H2B···O3iv0.972.413.120 (3)130
C2'—H2'1···O2'v0.972.493.247 (2)135
C4'—H4'···O3'vi0.982.483.375 (3)152
C2'—H2'2···O3'vii0.972.613.254 (2)124
C3'—H3'···O3'viii0.932.483.345 (3)156
Symmetry codes: (i) x+1/2, y+1/2, z; (ii) x−1/2, y+1/2, z; (iii) −x+1/2, y−1/2, −z+1; (iv) −x+1/2, y+1/2, −z+1; (v) x−1/2, y−1/2, z; (vi) x+1/2, y−1/2, z; (vii) −x+1/2, y−1/2, −z+2; (viii) −x+1/2, y+1/2, −z+2.
Acknowledgements top

The authors are grateful to the MICINN (CTQ2009–11172), Junta de Castilla y Leon, for financial support (GR178 and SA001A09) and for the doctoral fellowships awarded to MFF.

references
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