Skip to main content
NCBI home page
Acta Crystallographica Section E: Structure Reports Online logoLink to Acta Crystallographica Section E: Structure Reports Online
. 2012 Jul 10;68(Pt 8):o2410. doi: 10.1107/S1600536812030656

N-Benzyl-3,5-dide­oxy-3,5-imino-1,2-O-isopropyl­idene-β-l-lyxofuran­ose

David S Edgeley a, Sarah F Jenkinson b,*, Gabriel Lenagh-Snow b, Catherine Rutherford b, George W J Fleet b, Amber L Thompson a
PMCID: PMC3414331  PMID: 22904864

Abstract

X-ray crystallography confirmed the formation, structure and relative stereochemistry of the title compound, C15H19NO3, which contains a sterically congested four-membered azetidine ring system. The absolute configuration was determined by the use of l-arabinose as the starting material.

Related literature  

For related literature on azetidines, see: Krämer et al. (1997 ▶); Michaud et al. (1997a ▶,b ▶); Dekaris & Reissig (2010 ▶); Soengas et al. (2011 ▶); Jenkinson et al. (2011 ▶); Lenagh-Snow et al. (2011 ▶, 2012 ▶); Lee et al. (2012 ▶). For related literature on imino­sugars, see: Asano et al. (2000 ▶); Watson et al. (2001 ▶). For details of the cryostat, see: Cosier & Glazer (1986 ▶). For details of hydrogen refinement, see: Cooper et al. (2010 ▶). For references to the Chebychev polynomial, see: Prince (1982 ▶); Watkin (1994 ▶).graphic file with name e-68-o2410-scheme1.jpg

Experimental  

Crystal data  

  • C15H19NO3

  • M r = 261.32

  • Monoclinic, Inline graphic

  • a = 9.1674 (2) Å

  • b = 5.7551 (1) Å

  • c = 13.1112 (3) Å

  • β = 106.9544 (8)°

  • V = 661.67 (2) Å3

  • Z = 2

  • Mo Kα radiation

  • μ = 0.09 mm−1

  • T = 150 K

  • 0.24 × 0.23 × 0.07 mm

Data collection  

  • Nonius KappaCCD diffractometer

  • Absorption correction: multi-scan (DENZO and SCALEPACK; Otwinowski & Minor, 1997 ▶) T min = 0.94, T max = 0.99

  • 13110 measured reflections

  • 1638 independent reflections

  • 1544 reflections with I > 2σ(I)

  • R int = 0.014

Refinement  

  • R[F 2 > 2σ(F 2)] = 0.033

  • wR(F 2) = 0.087

  • S = 0.94

  • 1638 reflections

  • 172 parameters

  • 1 restraint

  • H-atom parameters constrained

  • Δρmax = 0.17 e Å−3

  • Δρmin = −0.18 e Å−3

Data collection: COLLECT (Nonius, 2001 ▶); cell refinement: DENZO and SCALEPACK (Otwinowski & Minor, 1997 ▶); data reduction: DENZO and SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ▶); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003 ▶); molecular graphics: CAMERON (Watkin et al., 1996 ▶); software used to prepare material for publication: CRYSTALS.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812030656/lh5500sup1.cif

e-68-o2410-sup1.cif (17.5KB, cif)

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812030656/lh5500Isup2.hkl

e-68-o2410-Isup2.hkl (103.2KB, hkl)

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

supplementary crystallographic information

Comment

Azetidines (Michaud et al., 1997a; Michaud et al., 1997b; Dekaris & Reissig, 2010; Soengas et al., 2011) are a relatively unstudied class of iminosugars (Asano et al., 2000; Watson et al., 2001, Michaud et al., 1997a; Michaud et al., 1997b; Dekaris & Reissig, 2010; Soengas et al., 2011) but initial results (Krämer et al., 1997; Lee et al., 2012) have shown some interesting biological activity.

Azetidine formation can be achieved by the double displacement of ditriflates with amines (Jenkinson et al., 2011; Lenagh-Snow et al., 2011; Lenagh-Snow et al., 2012). X-Ray crystallography confirmed the structure and relative stereochemistry of the formation of the title compound 3 (Fig. 1) from the displacement of a 3,5-O-ditriflate 2 with benzylamine. The absolute stereochemistry was determined by the use of L-arabinose as the starting material.

The five membered rings adopt envelope conformations with O7 and C10 out of the plane, and the azetidine ring adopts a puckered conformation (Fig. 2, Fig. 3).

Experimental

The title compound was recrystallized from cyclohexane/pentane. [α]D25 +76.0 (c 0.50 in CHCl3); m.p. 337–339 K.

Refinement

In the absence of significant anomalous scattering, Friedel pairs were merged and the absolute configuration was assigned from the starting material.

The H atoms were all located in a difference map, but those attached to carbon atoms were repositioned geometrically. The H atoms were initially refined with soft restraints on the bond lengths and angles to regularize their geometry (C—H in the range 0.93–0.98 Å) and Uiso(H) (in the range 1.2–1.5 times Ueq of the parent atom), after which the positions were refined with riding constraints (Cooper et al., 2010).

Figures

Fig. 1.

Fig. 1.

Open in a new tab

Synthetic Scheme.

Fig. 2.

Fig. 2.

Open in a new tab

The title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitrary radius.

Fig. 3.

Fig. 3.

Open in a new tab

Packing diagram of the title compound projected along the b-axis.

Crystal data

C15H19NO3 F(000) = 280
Mr = 261.32 Dx = 1.312 Mg m−3
Monoclinic, P21 Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb Cell parameters from 1627 reflections
a = 9.1674 (2) Å θ = 5–27°
b = 5.7551 (1) Å µ = 0.09 mm−1
c = 13.1112 (3) Å T = 150 K
β = 106.9544 (8)° Plate, colourless
V = 661.67 (2) Å3 0.24 × 0.23 × 0.07 mm
Z = 2
Open in a new tab

Data collection

Nonius KappaCCD diffractometer 1544 reflections with I > 2σ(I)
Graphite monochromator Rint = 0.014
ω scans θmax = 27.4°, θmin = 5.4°
Absorption correction: multi-scan (DENZO and SCALEPACK; Otwinowski & Minor, 1997) h = −11→11
Tmin = 0.94, Tmax = 0.99 k = −7→6
13110 measured reflections l = −16→16
1638 independent reflections
Open in a new tab

Refinement

Refinement on F2 Primary atom site location: structure-invariant direct methods
Least-squares matrix: full Hydrogen site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.033 H-atom parameters constrained
wR(F2) = 0.087 Method, part 1, Chebychev polynomial, (Watkin, 1994, Prince, 1982) [weight] = 1.0/[A0*T0(x) + A1*T1(x) ··· + An-1]*Tn-1(x)] where Ai are the Chebychev coefficients listed below and x = F /Fmax Method = Robust Weighting (Prince, 1982) W = [weight] * [1-(deltaF/6*sigmaF)2]2 Ai are: 22.1 34.0 17.6 5.07
S = 0.94 (Δ/σ)max = 0.0003286
1638 reflections Δρmax = 0.17 e Å−3
172 parameters Δρmin = −0.18 e Å−3
1 restraint
Open in a new tab

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1 K.
Open in a new tab

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

x y z Uiso*/Ueq
O1 0.09793 (13) 0.5625 (2) 0.84062 (10) 0.0269
C2 0.25050 (17) 0.6293 (3) 0.89568 (13) 0.0260
C3 0.35745 (18) 0.6618 (3) 0.82587 (13) 0.0262
N4 0.31206 (15) 0.5481 (3) 0.72006 (11) 0.0264
C5 0.45568 (19) 0.4116 (4) 0.74729 (15) 0.0318
C6 0.48402 (19) 0.4783 (3) 0.86494 (14) 0.0292
O7 0.42651 (14) 0.3113 (3) 0.92411 (10) 0.0319
C8 0.31601 (19) 0.4200 (3) 0.96665 (14) 0.0284
O9 0.19278 (13) 0.2728 (3) 0.96037 (10) 0.0313
C10 0.07349 (18) 0.3246 (3) 0.86343 (14) 0.0274
C11 0.0820 (2) 0.1650 (3) 0.77364 (14) 0.0306
C12 −0.07829 (19) 0.3058 (4) 0.88768 (15) 0.0333
C13 0.2813 (2) 0.6967 (3) 0.62624 (14) 0.0309
C14 0.2617 (2) 0.5526 (4) 0.52659 (14) 0.0288
C15 0.3343 (2) 0.6152 (4) 0.45124 (14) 0.0320
C16 0.3150 (2) 0.4828 (4) 0.35950 (14) 0.0353
C17 0.2236 (2) 0.2866 (4) 0.34202 (15) 0.0346
C18 0.1518 (2) 0.2208 (4) 0.41731 (16) 0.0379
C19 0.1714 (2) 0.3523 (4) 0.50899 (15) 0.0343
H21 0.2489 0.7722 0.9365 0.0300*
H31 0.3962 0.8232 0.8266 0.0305*
H51 0.4416 0.2480 0.7305 0.0388*
H52 0.5313 0.4779 0.7148 0.0374*
H61 0.5871 0.5325 0.9042 0.0348*
H81 0.3666 0.4639 1.0430 0.0337*
H112 0.0678 0.0054 0.7931 0.0457*
H113 0.0002 0.2059 0.7092 0.0453*
H111 0.1807 0.1782 0.7612 0.0454*
H121 −0.0909 0.1489 0.9112 0.0506*
H123 −0.1589 0.3444 0.8220 0.0494*
H122 −0.0782 0.4156 0.9454 0.0507*
H132 0.1871 0.7872 0.6208 0.0373*
H131 0.3679 0.8067 0.6310 0.0372*
H151 0.3977 0.7507 0.4630 0.0386*
H161 0.3646 0.5290 0.3064 0.0422*
H171 0.2100 0.2000 0.2782 0.0423*
H181 0.0896 0.0854 0.4067 0.0458*
H191 0.1208 0.3077 0.5589 0.0420*
Open in a new tab

Atomic displacement parameters (Å2)

U11 U22 U33 U12 U13 U23
O1 0.0214 (5) 0.0238 (6) 0.0331 (6) 0.0007 (5) 0.0041 (4) 0.0028 (5)
C2 0.0234 (7) 0.0239 (8) 0.0291 (7) −0.0006 (6) 0.0051 (6) −0.0014 (7)
C3 0.0234 (7) 0.0242 (8) 0.0299 (7) −0.0018 (6) 0.0063 (6) −0.0014 (6)
N4 0.0255 (6) 0.0246 (7) 0.0293 (7) −0.0002 (6) 0.0081 (5) −0.0014 (6)
C5 0.0287 (8) 0.0290 (9) 0.0385 (9) 0.0023 (7) 0.0108 (7) −0.0040 (8)
C6 0.0225 (7) 0.0289 (9) 0.0349 (8) −0.0002 (7) 0.0063 (6) −0.0003 (7)
O7 0.0293 (6) 0.0270 (6) 0.0393 (6) 0.0054 (5) 0.0100 (5) 0.0060 (6)
C8 0.0251 (7) 0.0274 (9) 0.0313 (8) 0.0014 (7) 0.0058 (6) 0.0036 (7)
O9 0.0264 (6) 0.0333 (7) 0.0311 (6) −0.0017 (5) 0.0034 (5) 0.0078 (5)
C10 0.0248 (7) 0.0257 (8) 0.0299 (8) −0.0007 (7) 0.0054 (6) 0.0049 (7)
C11 0.0291 (8) 0.0254 (8) 0.0361 (8) −0.0019 (7) 0.0077 (7) 0.0013 (7)
C12 0.0264 (7) 0.0366 (10) 0.0376 (8) −0.0030 (8) 0.0105 (6) 0.0037 (8)
C13 0.0365 (8) 0.0249 (8) 0.0318 (8) −0.0035 (8) 0.0106 (7) −0.0007 (7)
C14 0.0268 (7) 0.0279 (9) 0.0307 (8) 0.0010 (7) 0.0066 (6) −0.0015 (7)
C15 0.0289 (8) 0.0330 (10) 0.0326 (8) −0.0028 (8) 0.0069 (6) 0.0022 (7)
C16 0.0307 (8) 0.0430 (12) 0.0337 (9) 0.0009 (8) 0.0116 (7) 0.0003 (8)
C17 0.0306 (8) 0.0374 (10) 0.0342 (8) 0.0042 (8) 0.0070 (7) −0.0071 (8)
C18 0.0374 (9) 0.0322 (10) 0.0447 (10) −0.0062 (8) 0.0129 (8) −0.0080 (9)
C19 0.0357 (9) 0.0317 (10) 0.0379 (9) −0.0066 (8) 0.0147 (7) −0.0034 (8)
Open in a new tab

Geometric parameters (Å, º)

O1—C2 1.4271 (19) C11—H112 0.972
O1—C10 1.433 (2) C11—H113 0.981
C2—C3 1.535 (2) C11—H111 0.967
C2—C8 1.534 (2) C12—H121 0.972
C2—H21 0.984 C12—H123 0.983
C3—N4 1.480 (2) C12—H122 0.985
C3—C6 1.542 (2) C13—C14 1.513 (2)
C3—H31 0.994 C13—H132 0.993
N4—C5 1.484 (2) C13—H131 1.003
N4—C13 1.457 (2) C14—C15 1.390 (2)
C5—C6 1.536 (2) C14—C19 1.399 (3)
C5—H51 0.967 C15—C16 1.391 (3)
C5—H52 0.990 C15—H151 0.957
C6—O7 1.429 (2) C16—C17 1.385 (3)
C6—H61 0.986 C16—H161 0.974
O7—C8 1.435 (2) C17—C18 1.389 (3)
C8—O9 1.395 (2) C17—H171 0.950
C8—H81 1.005 C18—C19 1.387 (3)
O9—C10 1.4456 (19) C18—H181 0.952
C10—C11 1.513 (3) C19—H191 0.941
C10—C12 1.519 (2)
C2—O1—C10 109.99 (13) O9—C10—C12 107.79 (14)
O1—C2—C3 115.67 (13) O1—C10—C12 108.68 (15)
O1—C2—C8 104.34 (14) C11—C10—C12 112.21 (15)
C3—C2—C8 104.59 (14) C10—C11—H112 109.1
O1—C2—H21 109.4 C10—C11—H113 108.9
C3—C2—H21 109.7 H112—C11—H113 109.0
C8—C2—H21 113.1 C10—C11—H111 110.3
C2—C3—N4 116.83 (13) H112—C11—H111 108.8
C2—C3—C6 105.56 (14) H113—C11—H111 110.7
N4—C3—C6 89.27 (13) C10—C12—H121 109.5
C2—C3—H31 113.4 C10—C12—H123 107.6
N4—C3—H31 115.1 H121—C12—H123 111.0
C6—C3—H31 113.9 C10—C12—H122 108.6
C3—N4—C5 91.22 (12) H121—C12—H122 109.0
C3—N4—C13 117.65 (15) H123—C12—H122 111.1
C5—N4—C13 116.97 (14) N4—C13—C14 110.62 (16)
N4—C5—C6 89.30 (13) N4—C13—H132 108.6
N4—C5—H51 114.2 C14—C13—H132 110.1
C6—C5—H51 116.3 N4—C13—H131 111.3
N4—C5—H52 112.1 C14—C13—H131 107.0
C6—C5—H52 113.7 H132—C13—H131 109.2
H51—C5—H52 109.9 C13—C14—C15 120.71 (17)
C3—C6—C5 86.95 (13) C13—C14—C19 120.65 (16)
C3—C6—O7 106.25 (13) C15—C14—C19 118.64 (17)
C5—C6—O7 113.33 (15) C14—C15—C16 120.39 (18)
C3—C6—H61 118.1 C14—C15—H151 119.4
C5—C6—H61 117.3 C16—C15—H151 120.3
O7—C6—H61 112.3 C15—C16—C17 120.55 (17)
C6—O7—C8 109.39 (14) C15—C16—H161 120.0
C2—C8—O7 107.62 (14) C17—C16—H161 119.4
C2—C8—O9 105.91 (13) C16—C17—C18 119.59 (18)
O7—C8—O9 111.33 (16) C16—C17—H171 119.4
C2—C8—H81 113.1 C18—C17—H171 121.0
O7—C8—H81 108.9 C17—C18—C19 119.92 (19)
O9—C8—H81 110.0 C17—C18—H181 120.5
C8—O9—C10 108.58 (13) C19—C18—H181 119.6
O9—C10—O1 104.85 (14) C14—C19—C18 120.89 (17)
O9—C10—C11 111.18 (15) C14—C19—H191 119.8
O1—C10—C11 111.77 (14) C18—C19—H191 119.3
Open in a new tab

Hydrogen-bond geometry (Å, º)

D—H···A D—H H···A D···A D—H···A
C11—H111···N4 0.97 2.58 3.266 (3) 128
Open in a new tab

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: LH5500).

References

  1. Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst. 27, 435.
  2. Asano, N., Nash, R. J., Molyneuxl, R. J. & Fleet, G. W. J. (2000). Tetrahedron Asymmetry, 11, 1645–1680.
  3. Betteridge, P. W., Carruthers, J. R., Cooper, R. I., Prout, K. & Watkin, D. J. (2003). J. Appl. Cryst. 36, 1487.
  4. Cooper, R. I., Thompson, A. L. & Watkin, D. J. (2010). J. Appl. Cryst. 43, 1100–1107.
  5. Cosier, J. & Glazer, A. M. (1986). J. Appl. Cryst. 19, 105–107.
  6. Dekaris, V. & Reissig, H.-U. (2010). Synlett, pp. 42–46.
  7. Jenkinson, S. F., Lenagh-Snow, G. M. J., Fleet, G. W. J. & Thompson, A. L. (2011). Acta Cryst. E67, o2452. [DOI] [PMC free article] [PubMed]
  8. Krämer, B., Franz, T., Picasso, S., Pruschek, P. & Jäger, V. (1997). Synlett, pp. 95–97.
  9. Lee, J. C., Francis, S., Dutta, D., Gupta, V., Yang, Y., Zhu, J.-Y., Tash, J. S., Schonbrunn, E. & Georg, G. I. (2012). J. Org. Chem. 77, 3082–3098. [DOI] [PMC free article] [PubMed]
  10. Lenagh-Snow, G. M. J., Araujo, N., Jenkinson, S. F., Martinez, R. F., Shimada, Y., Yu, C.-Y., Kato, A. & Fleet, G. W. J. (2012). Org. Lett. 14, 2142–2145. [DOI] [PubMed]
  11. Lenagh-Snow, G. M. J., Araujo, N., Jenkinson, S. F., Rutherford, C., Nakagawa, S., Kato, A., Yu, C.-Y., Weymouth-Wilson, A. C. & Fleet, G. W. J. (2011). Org. Lett. 13, 5834–5837. [DOI] [PubMed]
  12. Michaud, T., Chanet-Ray, J., Chou, S. & Gelas, J. (1997a). Carbohydr. Res 299, 253–269.
  13. Michaud, T., Chanet-Ray, J., Chou, S. & Gelas, J. (1997b). Carbohydr. Res 303, 123–127.
  14. Nonius (2001). COLLECT Nonius BV, Delft, The Netherlands.
  15. Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307–326. New York: Academic Press.
  16. Prince, E. (1982). In Mathematical Techniques in Crystallography and Materials Science New York: Springer-Verlag.
  17. Soengas, R. G., Segade, Y., Jiménez, C. & Rodríguez, J. (2011). Tetrahedron, 67, 2617–2622.
  18. Watkin, D. (1994). Acta Cryst. A50, 411–437.
  19. Watkin, D. J., Prout, C. K. & Pearce, L. J. (1996). CAMERON Chemical Crystallography Laboratory, Oxford, England.
  20. Watson, A. A., Fleet, G. W. J., Asano, N., Molyneux, R. J. & Nash, R. J. (2001). Phytochemistry, 56, 265–295. [DOI] [PubMed]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812030656/lh5500sup1.cif

e-68-o2410-sup1.cif (17.5KB, cif)

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812030656/lh5500Isup2.hkl

e-68-o2410-Isup2.hkl (103.2KB, hkl)

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography

RESOURCES