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Acta Crystallogr Sect E Struct Rep Online. 2010 January 1; 66(Pt 1): o3.
Published online 2009 December 4. doi:  10.1107/S1600536809050892
PMCID: PMC2980103

(2S,4S)-3-Acryloyl-6-oxo-2-phenyl­perhydro­pyrimidine-4-carboxylic acid

Abstract

In the title compound, C14H14N2O4, the central six-membered ring adopts a twisted boat conformation with the phenyl substituent occupying an orthogonal position [dihedral angle = 86.88 (11)°]. In the crystal, mol­ecules are linked by carboxylic acid–carbonyl O—H(...)O and amide–carbonyl N—H(...)O hydrogen bonds, forming a three-dimensional network.

Related literature

For the synthesis from (S)-asparagine, see: Lakner & Negrete (2002 [triangle]). For background to water-soluble chiral auxiliaries, see: Mahindaratne et al. (2005a [triangle],b [triangle]). For conformational analysis, see: Cremer & Pople (1975 [triangle]).

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Object name is e-66-000o3-scheme1.jpg

Experimental

Crystal data

  • C14H14N2O4
  • M r = 274.27
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-66-000o3-efi1.jpg
  • a = 10.573 (5) Å
  • b = 10.670 (7) Å
  • c = 11.612 (5) Å
  • V = 1310.0 (12) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.10 mm−1
  • T = 98 K
  • 0.36 × 0.12 × 0.12 mm

Data collection

  • Rigaku AFC12/SATURN724 diffractometer
  • Absorption correction: multi-scan (ABSCOR; Higashi, 1995 [triangle]) T min = 0.496, T max = 1
  • 14053 measured reflections
  • 1573 independent reflections
  • 1547 reflections with I > 2σ(I)
  • R int = 0.033

Refinement

  • R[F 2 > 2σ(F 2)] = 0.038
  • wR(F 2) = 0.097
  • S = 1.11
  • 1573 reflections
  • 185 parameters
  • 1 restraint
  • H-atom parameters constrained
  • Δρmax = 0.20 e Å−3
  • Δρmin = −0.20 e Å−3

Data collection: CrystalClear (Rigaku/MSC, 2005 [triangle]); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: DIAMOND (Brandenburg, 2006 [triangle]); software used to prepare material for publication: publCIF (Westrip, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809050892/hg2611sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809050892/hg2611Isup2.hkl

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

supplementary crystallographic information

Comment

The title compound (I), was prepared as a part of an on-going program aimed at developing water-soluble chiral auxiliaries (Mahindaratne et al., 2005a,b). The development of effective, water-soluble chiral auxiliaries is attractive from an environmental standpoint. We have been investigating the use of asparagine-derived auxiliaries for asymmetry transfer in Diels-Alder cycloadditions under aqueous conditions. Herein, we report the structure of the derivative (I), which was prepared upon cyclocondensation of L-asparagine under basic conditions with benzaldehyde followed by in situ acryloylation (Fig. 1). Precipitation occurred on addition of HCl and washing the precipitate with cold water yielded analytically pure acrylamide, (I).

The central ring in (I) adopts a twisted boat conformation, Fig. 2, whereby the RMS of the N1, N3, C4 and C6 atom is 0.057 Å with the C2 and C5 atoms lying 0.499 (3) and 0.612 (3) Å, respectively out of plane. The ring-puckering parameters are q2 = 0.653 (2) Å, q3 = -0.043 (2) Å, Q = 0.654 (2) Å, and [var phi]2 = 49.76 (19)° (Cremer & Pople, 1975). The C21 substituents occupies an axial position whereas the C31, C41 and O6 substituents occupy equatorial positions. The phenyl ring occupies a position normal to the central ring as seen in the value of the dihedral angle between the two rings of 86.88 (11)°.

Two features are notable in the structure of (I). First, the crystal structure indicates the sole entrapment of the syn amide conformer of (I) (free acid of (II)-syn; Fig. 1). This is in contrast to the mixture of anti and syn conformers exhibited in aqueous sodium bicarbonate, in which anti conformer is favored by a ratio of 3:2 for (II) (sodium salt of (I)). The major conformer exhibited under these conditions was tentatively assigned as the anti conformer based on the stereochemistry of the major Diels-Alder product (2;S absolute configuration, Scheme 1), which is derived from the anti conformer of (II).

The crystal structure of (I) is stabilized by O–H···O and N–H···O hydrogen bonding, Table 1. Hydrogen bonds formed between the carboxylic acid-O41—H and carbonyl-O6 atoms leads to the formation of supramolecular chains aligned along the b axis, Fig. 3. The amide-N1—H hydrogen bonds to the carbonyl-O41 to form supramolecular chains aligned along the c axis, Fig. 4. Together, these hydrogen bonds consolidate molecules into a 3-D network, Fig. 5.

Experimental

Compound (I) was prepared following a literature procedure (Lakner & Negrete, 2002). Into a 100 ml flask was added L-asparagine monohydrate (7.51 g, 50 mmol) and aqueous NaOH (25.0 ml; 2.0 M, 1.0 equiv). The mixture was stirred for 15 min and benzaldehyde (5.1 ml; 50 mmol, 1.0 equiv) was added via syringe over 5 min. The mixture was stirred overnight and treated with solid sodium bicarbonate (8.4 g; 2.0 equiv) followed by cooling in an ice bath to 273 K. To the vigorously stirred cold solution acryloyl chloride (5.3 ml; 65.5 mmol, 1.3 equiv) was added slowly (5 portions over 1 h). Cooling and stirring were continued an additional 2 h, after which the mixture was treated with HCl (10%, 1.6 equiv), inducing precipitation of (I). The product was filtered, washed with ice-cold water, and dried overnight under high vacuum to obtain (I) as an amorphous white powder (53% yield). The solid was crystallized twice in slow evaporating methanol to yield white crystals: M. pt: 457 K (dec.); [α]D 24.3: -23.5° (c = 1 g cm-3, methanol); 1H NMR (sat. NaHCO3/D2O, 500 MHz; the observation of separate signals for C2—H is suggestive of two conformers): δ 2.2–2.8 (m, 2H), 4.6–4.8 (two br s, 1H), 5.93 (br d, 1H), 6.36 (d, J = 17.0 Hz, 1H), 6.60 (br s, 0.4H; signal for the minor conformer of C2—H), 6.65 (dd, J = 10.0, 17.0 Hz, 1H), 6.90 (br s, 0.6H; signal for the major conformer of C2—H) 7.4–7.8 (m, 5H). 13C NMR (sat. NaHCO3/D2O, 125 MHz): δ 33.5, 55.5, 126.6, 127.6, 128.7, 130.2, 138.2, 160.5, 169.2, 173.9, 176.7; IR (νmax, cm-1): 3355, 1716, 1645, 1416, 1356, 629; Anal. Calcd for C14H14N2O4: C, 61.31; H, 5.14; N, 10.21. Found: C, 60.79; H, 5.05; N, 10.10%.

Single crystals were obtained by slow evaporation of a methanol solution of (I).

Refinement

The H atoms were geometrically placed (O—H = 0.84 Å, N–H = 0.88 Å, and C—H = 0.95–1.00 Å) and refined as riding with Uiso(H) = 1.2–1.5Ueq(parent atom). In the absence of significant anomalous scattering effects, 1149 Friedel pairs were averaged in the final refinement. The absolute configuration was determined on the basis of the absolute stereochemistry of (S)-asparagine, a reagent employed in the synthesis.

Figures

Fig. 1.
Reaction scheme.
Fig. 2.
Molecular structure of (I), showing atom-labelling scheme and displacement ellipsoids at the 50% probability level.
Fig. 3.
Supramolecular chain aligned along the b axis mediated by O–H···O hydrogen bonds (orange dashed lines). Color code: oxygen, red; nitrogen, blue; carbon, grey; and hydrogen, green.
Fig. 4.
Supramolecular chain aligned along the c axis mediated by N–H···O hydrogen bonds (blue dashed lines). Color code: oxygen, red; nitrogen, blue; carbon, grey; and hydrogen, green.
Fig. 5.
Unit-cell contents viewed in projection down the c axis. The O–H···O and N–H···O hydrogen bonds are shown as orange and blue dashed lines, respectively.

Crystal data

C14H14N2O4F(000) = 576
Mr = 274.27Dx = 1.391 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71069 Å
Hall symbol: P 2ac 2abCell parameters from 4478 reflections
a = 10.573 (5) Åθ = 1.9–30.4°
b = 10.670 (7) ŵ = 0.10 mm1
c = 11.612 (5) ÅT = 98 K
V = 1310.0 (12) Å3Block, colourless
Z = 40.36 × 0.12 × 0.12 mm

Data collection

Rigaku AFC12K/SATURN724 diffractometer1573 independent reflections
Radiation source: fine-focus sealed tube1547 reflections with I > 2σ(I)
graphiteRint = 0.033
ω scansθmax = 26.5°, θmin = 2.6°
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)h = −11→13
Tmin = 0.496, Tmax = 1k = −13→13
14053 measured reflectionsl = −13→14

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.038H-atom parameters constrained
wR(F2) = 0.097w = 1/[σ2(Fo2) + (0.0562P)2 + 0.3429P] where P = (Fo2 + 2Fc2)/3
S = 1.11(Δ/σ)max < 0.001
1573 reflectionsΔρmax = 0.20 e Å3
185 parametersΔρmin = −0.20 e Å3
1 restraintExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.009 (2)

Special details

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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)

xyzUiso*/Ueq
O60.81404 (14)0.17595 (13)0.43043 (13)0.0272 (4)
O310.97062 (14)0.69803 (15)0.42240 (13)0.0280 (4)
O410.90743 (14)0.61359 (15)0.17482 (13)0.0292 (4)
O421.09113 (14)0.52210 (15)0.21965 (13)0.0281 (4)
H42o1.11710.57030.16760.042*
N10.73021 (17)0.36445 (17)0.46856 (15)0.0242 (4)
H10.70030.33810.53500.029*
N30.82135 (16)0.55157 (16)0.39712 (15)0.0230 (4)
C40.91724 (19)0.4760 (2)0.33983 (17)0.0228 (4)
H40.98770.46020.39540.027*
C50.8624 (2)0.3497 (2)0.30244 (18)0.0243 (4)
H5A0.79950.36260.24040.029*
H5B0.93070.29550.27210.029*
C60.80012 (19)0.2871 (2)0.40449 (18)0.0238 (4)
C20.70244 (19)0.49147 (19)0.43056 (18)0.0232 (4)
H20.66790.53840.49820.028*
C210.60132 (19)0.49244 (19)0.33662 (18)0.0245 (4)
C220.6093 (2)0.5707 (2)0.24203 (19)0.0297 (5)
H220.67950.62540.23350.036*
C230.5135 (2)0.5692 (3)0.1587 (2)0.0337 (5)
H230.51920.62310.09390.040*
C240.4116 (2)0.4907 (2)0.1699 (2)0.0361 (6)
H240.34790.48880.11220.043*
C250.4020 (2)0.4142 (2)0.2656 (3)0.0435 (7)
H250.33080.36080.27450.052*
C260.4962 (2)0.4155 (2)0.3487 (3)0.0372 (6)
H260.48870.36320.41460.045*
C310.86129 (19)0.6649 (2)0.43839 (18)0.0236 (4)
C320.7670 (2)0.7439 (2)0.4996 (2)0.0274 (5)
H320.67950.73330.48390.033*
C330.8035 (2)0.8280 (2)0.5748 (2)0.0380 (6)
H33A0.89090.83890.59070.046*
H33B0.74250.87800.61340.046*
C410.97069 (19)0.5461 (2)0.23591 (17)0.0232 (4)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O60.0262 (8)0.0274 (7)0.0281 (7)0.0023 (6)0.0043 (6)0.0022 (6)
O310.0197 (7)0.0332 (8)0.0311 (8)−0.0026 (6)−0.0005 (6)−0.0024 (7)
O410.0213 (7)0.0410 (9)0.0253 (7)−0.0003 (7)−0.0024 (6)0.0056 (7)
O420.0215 (7)0.0319 (8)0.0310 (8)0.0003 (7)0.0069 (7)0.0045 (7)
N10.0233 (9)0.0262 (8)0.0229 (8)0.0022 (7)0.0041 (7)0.0026 (7)
N30.0168 (8)0.0277 (9)0.0245 (8)−0.0006 (7)0.0022 (7)−0.0029 (7)
C40.0172 (9)0.0279 (10)0.0232 (9)−0.0008 (8)0.0011 (8)−0.0005 (8)
C50.0215 (10)0.0274 (10)0.0242 (10)0.0014 (8)0.0019 (8)−0.0026 (8)
C60.0170 (9)0.0300 (10)0.0243 (10)−0.0009 (8)−0.0011 (8)−0.0016 (8)
C20.0197 (10)0.0250 (9)0.0248 (9)0.0010 (8)0.0022 (8)−0.0010 (8)
C210.0203 (10)0.0247 (10)0.0285 (10)0.0029 (8)0.0022 (9)−0.0036 (8)
C220.0208 (10)0.0396 (12)0.0287 (10)−0.0018 (9)0.0014 (8)0.0021 (10)
C230.0254 (11)0.0457 (13)0.0301 (11)0.0046 (10)−0.0002 (9)0.0004 (11)
C240.0241 (11)0.0404 (13)0.0438 (13)0.0063 (10)−0.0094 (11)−0.0102 (11)
C250.0276 (12)0.0316 (12)0.0714 (19)−0.0058 (10)−0.0108 (13)0.0022 (13)
C260.0246 (12)0.0322 (11)0.0549 (15)−0.0031 (10)−0.0044 (11)0.0088 (11)
C310.0198 (10)0.0279 (10)0.0231 (10)−0.0007 (8)−0.0013 (8)−0.0009 (8)
C320.0223 (10)0.0287 (10)0.0310 (10)−0.0010 (9)0.0032 (8)−0.0009 (9)
C330.0289 (12)0.0407 (13)0.0445 (14)−0.0019 (10)0.0046 (11)−0.0134 (11)
C410.0178 (10)0.0288 (10)0.0230 (9)−0.0025 (8)−0.0001 (8)−0.0037 (8)

Geometric parameters (Å, °)

O6—C61.233 (3)C2—H21.0000
O31—C311.223 (3)C21—C221.382 (3)
O41—C411.212 (3)C21—C261.389 (3)
O42—C411.313 (3)C22—C231.400 (3)
O42—H42o0.8400C22—H220.9500
N1—C61.334 (3)C23—C241.371 (3)
N1—C21.455 (3)C23—H230.9500
N1—H10.8800C24—C251.383 (4)
N3—C311.367 (3)C24—H240.9500
N3—C41.456 (3)C25—C261.387 (4)
N3—C21.464 (3)C25—H250.9500
C4—C411.528 (3)C26—H260.9500
C4—C51.530 (3)C31—C321.486 (3)
C4—H41.0000C32—C331.310 (3)
C5—C61.511 (3)C32—H320.9500
C5—H5A0.9900C33—H33A0.9500
C5—H5B0.9900C33—H33B0.9500
C2—C211.527 (3)
C41—O42—H42o107.5C22—C21—C2121.94 (19)
C6—N1—C2121.25 (18)C26—C21—C2118.9 (2)
C6—N1—H1119.4C21—C22—C23119.9 (2)
C2—N1—H1119.4C21—C22—H22120.1
C31—N3—C4115.77 (17)C23—C22—H22120.1
C31—N3—C2124.03 (17)C24—C23—C22120.6 (2)
C4—N3—C2118.46 (16)C24—C23—H23119.7
N3—C4—C41110.29 (17)C22—C23—H23119.7
N3—C4—C5110.71 (16)C23—C24—C25119.6 (2)
C41—C4—C5110.33 (17)C23—C24—H24120.2
N3—C4—H4108.5C25—C24—H24120.2
C41—C4—H4108.5C24—C25—C26120.1 (2)
C5—C4—H4108.5C24—C25—H25120.0
C6—C5—C4109.38 (17)C26—C25—H25120.0
C6—C5—H5A109.8C25—C26—C21120.7 (2)
C4—C5—H5A109.8C25—C26—H26119.7
C6—C5—H5B109.8C21—C26—H26119.7
C4—C5—H5B109.8O31—C31—N3119.6 (2)
H5A—C5—H5B108.2O31—C31—C32122.9 (2)
O6—C6—N1121.7 (2)N3—C31—C32117.51 (19)
O6—C6—C5124.39 (19)C33—C32—C31120.7 (2)
N1—C6—C5113.90 (18)C33—C32—H32119.7
N1—C2—N3108.37 (16)C31—C32—H32119.7
N1—C2—C21111.35 (16)C32—C33—H33A120.0
N3—C2—C21114.12 (17)C32—C33—H33B120.0
N1—C2—H2107.6H33A—C33—H33B120.0
N3—C2—H2107.6O41—C41—O42124.6 (2)
C21—C2—H2107.6O41—C41—C4123.30 (19)
C22—C21—C26119.1 (2)O42—C41—C4112.13 (18)
C31—N3—C4—C41−60.1 (2)N3—C2—C21—C26166.10 (19)
C2—N3—C4—C41134.34 (18)C26—C21—C22—C23−1.6 (3)
C31—N3—C4—C5177.53 (17)C2—C21—C22—C23−179.3 (2)
C2—N3—C4—C511.9 (2)C21—C22—C23—C240.0 (4)
N3—C4—C5—C6−52.8 (2)C22—C23—C24—C251.4 (4)
C41—C4—C5—C6−175.13 (16)C23—C24—C25—C26−1.2 (4)
C2—N1—C6—O6−172.90 (19)C24—C25—C26—C21−0.5 (4)
C2—N1—C6—C59.2 (3)C22—C21—C26—C251.8 (4)
C4—C5—C6—O6−134.5 (2)C2—C21—C26—C25179.6 (2)
C4—C5—C6—N143.3 (2)C4—N3—C31—O312.4 (3)
C6—N1—C2—N3−50.5 (2)C2—N3—C31—O31167.06 (19)
C6—N1—C2—C2175.8 (2)C4—N3—C31—C32−178.79 (18)
C31—N3—C2—N1−127.48 (19)C2—N3—C31—C32−14.1 (3)
C4—N3—C2—N136.8 (2)O31—C31—C32—C33−25.7 (4)
C31—N3—C2—C21107.8 (2)N3—C31—C32—C33155.5 (2)
C4—N3—C2—C21−87.9 (2)N3—C4—C41—O41−35.8 (3)
N1—C2—C21—C22−139.2 (2)C5—C4—C41—O4186.9 (2)
N3—C2—C21—C22−16.2 (3)N3—C4—C41—O42145.80 (17)
N1—C2—C21—C2643.0 (3)C5—C4—C41—O42−91.6 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1···O41i0.882.052.812 (3)144
O42—H42o···O6ii0.841.762.596 (3)173

Symmetry codes: (i) −x+3/2, −y+1, z+1/2; (ii) −x+2, y+1/2, −z+1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HG2611).

References

  • Brandenburg, K. (2006). DIAMOND Crystal Impact GbR, Bonn, Germany.
  • Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc.97, 1354–1358.
  • Higashi, T. (1995). ABSCOR Rigaku Corporation, Tokyo, Japan.
  • Lakner, F. J. & Negrete, G. R. (2002). Synlett, 4, 643–645.
  • Mahindaratne, M. P. D., Quinõnes, B. A., Recio, A. III, Rodriguez, E. A., Lakner, F. J. & Negrete, G. R. (2005a). Arkivoc, 6, 321–328.
  • Mahindaratne, M. P. D., Quinõnes, B. A., Recio, A. III, Rodriguez, E. A., Lakner, F. J. & Negrete, G. R. (2005b). Tetrahedron, 61, 9495–9501.
  • Rigaku/MSC (2005). CrystalClear Rigaku/MSC Inc., The Woodlands, Texas, USA.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Westrip, S. P. (2009). publCIF In preparation.

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