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organic compounds
(4R)-4-[(1R)-1,2-Dihydroxyethyl]-1-[(1R)-1-phenylethyl]pyrrolidin-2-one
aCancer Research Laboratory, The University of Auckland, Private Bag 92019, Auckland, New Zealand, and bDepartment of Chemistry, The University of Auckland, Private Bag 92019, Auckland, New Zealand
*Correspondence e-mail: pdw.boyd@auckland.ac.nz
The title compound, C14H19NO3, was obtained as one of the two isomers of a Sharpless asymmetric dihydroxylation reaction of (1S)-1-[(1R)-1-phenylethyl]-4-vinylpyrrolidin-2-one. The absolute stereochemistry of this isomer was determined from the known stereochemistry (R) at the bridge C atom between the phenyl and pyrrolidine rings. The molecules form one-dimensional tapes along the b axis via hydrogen bonding between the carbonyl O atom and the alcohol groups of neighbouring molecules. These assemble into sheets via interdigitative stacking of the phenyl rings and C—H⋯O interactions.
Experimental
Crystal data
|
Data collection
|
Refinement
|
|
Data collection: SMART (Siemens, 1995); cell SAINT (Siemens, 1995
); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008
); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008
); molecular graphics: ORTEPIII (Burnett & Johnson, 1996
) and Mercury (Macrae et al., 2006
); software used to prepare material for publication: WinGX (Farrugia, 1999
).
Supporting information
10.1107/S1600536808027293/at2618sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536808027293/at2618Isup2.hkl
(4R)-4-[(1R)-1,2-Dihydroxyethyl]-1-[(1R)-1-phenylethyl]-2-pyrrolidinone (I): AD-mix-β (1.40 g, 1 mmol, Aldrich Cat. No. 392766) was dissolved in tert-butanol (5 ml) and water (5 ml). Methanesulfonamide (98 mg, 1 mmol) was added and cooled to 273 K, (1S)-1-((1R)-1-phenylethyl)-4-vinylpyrrolidin-2-one1 (216 mg, 1 mmol) was added and the reaction stirred for 24 h. Na2SO3 (1.5 g, 11.9 mmol) was added and stirred for another 90 minutes. The reaction was extracted with dichloromethane (4x100 ml), the combined organic layers were washed with 2 N KOH solution, dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by eluting with methanol/ethylacetate (3:7) to give the two isomers (4R)-4-[(1R)-1,2-dihydroxyethyl]-1-[(1R)-1-phenylethyl]-2-pyrrolidinone and (4R)-4-[(1S)-1,2-dihydroxyethyl]-1-[(1R)-1-phenylethyl]-2-pyrrolidinone (169 mg, 68%) in a ratio of 2:1. The title compound (I) was then obtained by recrystallization from ethylacetate as clear crystals. 1H NMR (400 MHz, CDCl3) δ 7.36–7.24 (m, 5 H), 5.47 (q, J=7.1 Hz, 1 H), 3.69 (dd, J=10.7, 2.8 Hz, 1 H), 3.67–3.60 (m, 1 H), 3.46 (dd, J=10.7, 7.0 Hz, 1 H), 3.35 (dd, J=10.0, 7.0 Hz, 1 H), 3.13 (dd, J=10.0, 8.0 Hz, 1 H), 2.66 (br s, 1 H), 2.46 (dd, J=15.2, 8.1 Hz, 1 H), 2.40–2.29 (m, 1 H), 2.26 (dd, J=15.2, 8.2 Hz, 1 H), 2.17 (br s, 1 H), 1.53 (t, J=7.1 Hz, 3 H). LCMS (APCI+) calcd for C14H19NO3: 250 (MH+), found 250 (100%).
Hydrogen atoms were placed in calculated positions and refined using the riding model [O—H = 0.82 Å C—H = 0.93–0.97 Å], with Uiso(H) = 1.5 times Ueq(O) and Uiso(H) = 1.2 or 1.5 times Ueq(C)..
Data collection: SMART (Siemens, 1995); cell
SAINT (Siemens, 1995); data reduction: SAINT (Siemens, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPIII (Burnett & Johnson, 1996) and Mercury (Macrae et al., 2006); software used to prepare material for publication: WinGX (Farrugia, 1999). ![]() | Fig. 1. Structure of (I) showing 50% probability displacement ellipsoids for non-hydrogen atoms and hydrogen atoms as arbitary spheres. |
![]() | Fig. 2. Illustration of the arrangement of (I) into sheets. |
C14H19NO3 | F(000) = 268 |
Mr = 249.30 | Dx = 1.248 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2yb | Cell parameters from 2597 reflections |
a = 6.1953 (1) Å | θ = 1.6–26.4° |
b = 8.2895 (2) Å | µ = 0.09 mm−1 |
c = 13.2737 (1) Å | T = 83 K |
β = 103.353 (2)° | Plate, colourless |
V = 663.25 (2) Å3 | 0.28 × 0.18 × 0.10 mm |
Z = 2 |
Siemens SMART APEX CCD diffractometer | 1271 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.040 |
Graphite monochromator | θmax = 26.4°, θmin = 1.6° |
ω scans | h = −7→7 |
4016 measured reflections | k = −10→10 |
1461 independent reflections | l = −7→16 |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.045 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.099 | H-atom parameters constrained |
S = 1.01 | w = 1/[σ2(Fo2) + (0.0168P)2 + 0.6853P] where P = (Fo2 + 2Fc2)/3 |
1461 reflections | (Δ/σ)max < 0.001 |
166 parameters | Δρmax = 0.20 e Å−3 |
1 restraint | Δρmin = −0.22 e Å−3 |
C14H19NO3 | V = 663.25 (2) Å3 |
Mr = 249.30 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 6.1953 (1) Å | µ = 0.09 mm−1 |
b = 8.2895 (2) Å | T = 83 K |
c = 13.2737 (1) Å | 0.28 × 0.18 × 0.10 mm |
β = 103.353 (2)° |
Siemens SMART APEX CCD diffractometer | 1271 reflections with I > 2σ(I) |
4016 measured reflections | Rint = 0.040 |
1461 independent reflections |
R[F2 > 2σ(F2)] = 0.045 | 1 restraint |
wR(F2) = 0.099 | H-atom parameters constrained |
S = 1.01 | Δρmax = 0.20 e Å−3 |
1461 reflections | Δρmin = −0.22 e Å−3 |
166 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
O3 | 0.1980 (4) | −0.0064 (3) | 0.00048 (16) | 0.0261 (5) | |
H3 | 0.2059 | 0.0736 | −0.0348 | 0.039* | |
O1 | 0.3278 (5) | −0.7778 (3) | −0.12286 (19) | 0.0277 (6) | |
O2 | 0.3068 (5) | −0.0804 (3) | −0.20720 (19) | 0.0339 (6) | |
H2 | 0.3289 | 0.0108 | −0.1832 | 0.051* | |
N1 | 0.4081 (4) | −0.5848 (3) | −0.2318 (2) | 0.0200 (6) | |
C11 | 0.2531 (5) | −0.4926 (4) | −0.0993 (2) | 0.0204 (6) | |
H11A | 0.3554 | −0.4685 | −0.0339 | 0.024* | |
H11B | 0.1070 | −0.5120 | −0.0869 | 0.024* | |
C7 | 0.5155 (5) | −0.6928 (4) | −0.2932 (2) | 0.0216 (7) | |
H7 | 0.4748 | −0.8031 | −0.2784 | 0.026* | |
C13 | 0.3005 (6) | −0.1917 (4) | −0.1258 (3) | 0.0231 (7) | |
H13 | 0.4473 | −0.1964 | −0.0784 | 0.028* | |
C9 | 0.4141 (6) | −0.4083 (4) | −0.2397 (3) | 0.0231 (7) | |
H9A | 0.3682 | −0.3731 | −0.3112 | 0.028* | |
H9B | 0.5613 | −0.3666 | −0.2099 | 0.028* | |
C12 | 0.3308 (5) | −0.6349 (4) | −0.1506 (2) | 0.0216 (7) | |
C1 | 0.4215 (5) | −0.6645 (4) | −0.4075 (2) | 0.0222 (7) | |
C8 | 0.7661 (5) | −0.6810 (5) | −0.2569 (3) | 0.0320 (8) | |
H8A | 0.8137 | −0.5754 | −0.2721 | 0.048* | |
H8B | 0.8341 | −0.7605 | −0.2922 | 0.048* | |
H8C | 0.8089 | −0.6998 | −0.1837 | 0.048* | |
C10 | 0.2466 (6) | −0.3545 (4) | −0.1767 (3) | 0.0217 (7) | |
H10 | 0.0983 | −0.3499 | −0.2228 | 0.026* | |
C6 | 0.5480 (6) | −0.6089 (4) | −0.4737 (2) | 0.0297 (8) | |
H6 | 0.6968 | −0.5842 | −0.4474 | 0.036* | |
C14 | 0.1299 (6) | −0.1421 (4) | −0.0656 (2) | 0.0236 (7) | |
H14A | −0.0084 | −0.1162 | −0.1142 | 0.028* | |
H14B | 0.1024 | −0.2326 | −0.0240 | 0.028* | |
C4 | 0.2361 (7) | −0.6207 (6) | −0.6180 (3) | 0.0433 (10) | |
H4 | 0.1743 | −0.6056 | −0.6882 | 0.052* | |
C2 | 0.2008 (6) | −0.6969 (6) | −0.4493 (3) | 0.0395 (10) | |
H2A | 0.1129 | −0.7347 | −0.4063 | 0.047* | |
C5 | 0.4561 (7) | −0.5893 (5) | −0.5789 (3) | 0.0370 (9) | |
H5 | 0.5444 | −0.5548 | −0.6227 | 0.044* | |
C3 | 0.1060 (7) | −0.6746 (7) | −0.5538 (3) | 0.0491 (12) | |
H3A | −0.0438 | −0.6959 | −0.5801 | 0.059* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O3 | 0.0388 (14) | 0.0189 (12) | 0.0245 (11) | −0.0048 (12) | 0.0151 (10) | −0.0050 (11) |
O1 | 0.0460 (16) | 0.0153 (12) | 0.0264 (13) | −0.0007 (11) | 0.0178 (12) | 0.0004 (10) |
O2 | 0.0633 (18) | 0.0161 (12) | 0.0291 (13) | −0.0033 (14) | 0.0247 (13) | −0.0008 (10) |
N1 | 0.0294 (15) | 0.0130 (13) | 0.0208 (13) | −0.0012 (12) | 0.0121 (11) | −0.0019 (11) |
C11 | 0.0293 (16) | 0.0170 (15) | 0.0176 (14) | −0.0016 (15) | 0.0111 (12) | −0.0007 (14) |
C7 | 0.0299 (17) | 0.0168 (17) | 0.0202 (15) | 0.0016 (15) | 0.0103 (13) | −0.0010 (13) |
C13 | 0.0341 (18) | 0.0166 (16) | 0.0219 (16) | −0.0032 (15) | 0.0135 (14) | −0.0008 (14) |
C9 | 0.035 (2) | 0.0168 (16) | 0.0211 (16) | −0.0030 (15) | 0.0134 (14) | −0.0025 (14) |
C12 | 0.0269 (17) | 0.0193 (16) | 0.0196 (15) | −0.0028 (14) | 0.0071 (13) | −0.0005 (14) |
C1 | 0.0292 (17) | 0.0180 (17) | 0.0203 (15) | 0.0016 (14) | 0.0073 (13) | −0.0056 (14) |
C8 | 0.0330 (19) | 0.038 (2) | 0.0248 (17) | 0.0042 (18) | 0.0050 (14) | −0.0050 (16) |
C10 | 0.0309 (19) | 0.0178 (16) | 0.0191 (16) | −0.0010 (15) | 0.0112 (14) | −0.0004 (13) |
C6 | 0.041 (2) | 0.0249 (19) | 0.0255 (17) | −0.0037 (17) | 0.0125 (15) | 0.0010 (16) |
C14 | 0.0327 (18) | 0.0182 (16) | 0.0225 (15) | −0.0025 (14) | 0.0116 (13) | −0.0022 (14) |
C4 | 0.059 (3) | 0.044 (3) | 0.0239 (17) | 0.014 (2) | 0.0029 (17) | −0.0049 (18) |
C2 | 0.034 (2) | 0.060 (3) | 0.0269 (18) | −0.003 (2) | 0.0112 (15) | −0.011 (2) |
C5 | 0.063 (3) | 0.0251 (19) | 0.0269 (18) | 0.001 (2) | 0.0178 (18) | 0.0022 (16) |
C3 | 0.035 (2) | 0.075 (4) | 0.034 (2) | 0.002 (2) | 0.0001 (17) | −0.017 (2) |
O3—C14 | 1.429 (4) | C9—H9A | 0.9700 |
O3—H3 | 0.8200 | C9—H9B | 0.9700 |
O1—C12 | 1.242 (4) | C1—C2 | 1.378 (5) |
O2—C13 | 1.428 (4) | C1—C6 | 1.385 (4) |
O2—H2 | 0.8200 | C8—H8A | 0.9600 |
N1—C12 | 1.342 (4) | C8—H8B | 0.9600 |
N1—C9 | 1.468 (4) | C8—H8C | 0.9600 |
N1—C7 | 1.469 (4) | C10—H10 | 0.9800 |
C11—C12 | 1.496 (5) | C6—C5 | 1.390 (5) |
C11—C10 | 1.532 (4) | C6—H6 | 0.9300 |
C11—H11A | 0.9700 | C14—H14A | 0.9700 |
C11—H11B | 0.9700 | C14—H14B | 0.9700 |
C7—C1 | 1.513 (4) | C4—C5 | 1.367 (6) |
C7—C8 | 1.519 (5) | C4—C3 | 1.376 (6) |
C7—H7 | 0.9800 | C4—H4 | 0.9300 |
C13—C10 | 1.511 (5) | C2—C3 | 1.388 (5) |
C13—C14 | 1.521 (4) | C2—H2A | 0.9300 |
C13—H13 | 0.9800 | C5—H5 | 0.9300 |
C9—C10 | 1.542 (5) | C3—H3A | 0.9300 |
C14—O3—H3 | 109.5 | C6—C1—C7 | 123.0 (3) |
C13—O2—H2 | 109.5 | C7—C8—H8A | 109.5 |
C12—N1—C9 | 112.7 (3) | C7—C8—H8B | 109.5 |
C12—N1—C7 | 123.2 (3) | H8A—C8—H8B | 109.5 |
C9—N1—C7 | 123.1 (3) | C7—C8—H8C | 109.5 |
C12—C11—C10 | 104.2 (2) | H8A—C8—H8C | 109.5 |
C12—C11—H11A | 110.9 | H8B—C8—H8C | 109.5 |
C10—C11—H11A | 110.9 | C13—C10—C11 | 113.5 (3) |
C12—C11—H11B | 110.9 | C13—C10—C9 | 113.2 (3) |
C10—C11—H11B | 110.9 | C11—C10—C9 | 103.3 (3) |
H11A—C11—H11B | 108.9 | C13—C10—H10 | 108.9 |
N1—C7—C1 | 110.1 (3) | C11—C10—H10 | 108.9 |
N1—C7—C8 | 110.3 (3) | C9—C10—H10 | 108.9 |
C1—C7—C8 | 115.9 (3) | C1—C6—C5 | 121.0 (3) |
N1—C7—H7 | 106.7 | C1—C6—H6 | 119.5 |
C1—C7—H7 | 106.7 | C5—C6—H6 | 119.5 |
C8—C7—H7 | 106.7 | O3—C14—C13 | 113.2 (3) |
O2—C13—C10 | 106.3 (3) | O3—C14—H14A | 108.9 |
O2—C13—C14 | 111.5 (3) | C13—C14—H14A | 108.9 |
C10—C13—C14 | 111.6 (3) | O3—C14—H14B | 108.9 |
O2—C13—H13 | 109.1 | C13—C14—H14B | 108.9 |
C10—C13—H13 | 109.1 | H14A—C14—H14B | 107.8 |
C14—C13—H13 | 109.1 | C5—C4—C3 | 120.1 (4) |
N1—C9—C10 | 102.6 (3) | C5—C4—H4 | 119.9 |
N1—C9—H9A | 111.2 | C3—C4—H4 | 119.9 |
C10—C9—H9A | 111.2 | C1—C2—C3 | 121.9 (4) |
N1—C9—H9B | 111.2 | C1—C2—H2A | 119.1 |
C10—C9—H9B | 111.2 | C3—C2—H2A | 119.1 |
H9A—C9—H9B | 109.2 | C4—C5—C6 | 120.0 (3) |
O1—C12—N1 | 124.5 (3) | C4—C5—H5 | 120.0 |
O1—C12—C11 | 126.1 (3) | C6—C5—H5 | 120.0 |
N1—C12—C11 | 109.5 (3) | C4—C3—C2 | 119.3 (4) |
C2—C1—C6 | 117.6 (3) | C4—C3—H3A | 120.4 |
C2—C1—C7 | 119.3 (3) | C2—C3—H3A | 120.4 |
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3···O1i | 0.82 | 1.96 | 2.743 (3) | 158 |
O2—H2···O1i | 0.82 | 1.93 | 2.738 (3) | 170 |
Symmetry code: (i) x, y+1, z. |
Experimental details
Crystal data | |
Chemical formula | C14H19NO3 |
Mr | 249.30 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 83 |
a, b, c (Å) | 6.1953 (1), 8.2895 (2), 13.2737 (1) |
β (°) | 103.353 (2) |
V (Å3) | 663.25 (2) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.28 × 0.18 × 0.10 |
Data collection | |
Diffractometer | Siemens SMART APEX CCD diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 4016, 1461, 1271 |
Rint | 0.040 |
(sin θ/λ)max (Å−1) | 0.626 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.045, 0.099, 1.01 |
No. of reflections | 1461 |
No. of parameters | 166 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.20, −0.22 |
Computer programs: SMART (Siemens, 1995), SAINT (Siemens, 1995), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEPIII (Burnett & Johnson, 1996) and Mercury (Macrae et al., 2006), WinGX (Farrugia, 1999).
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3···O1i | 0.82 | 1.96 | 2.743 (3) | 158.3 |
O2—H2···O1i | 0.82 | 1.93 | 2.738 (3) | 169.7 |
Symmetry code: (i) x, y+1, z. |
Acknowledgements
This work was supported by the Auckland Division of the Cancer Society of New Zealand, UniServices and the University of Auckland Research Committee.
References
Burnett, M. N. & Johnson, C. K. (1996). ORTEPIII. Report ORNL-6895. Oak Ridge National Laboratory, Tennessee, USA. Google Scholar
Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838. CrossRef CAS IUCr Journals Google Scholar
Fava, C., Galeazzi, R., Mobbili, G. & Orena, M. (1999). Heterocycles, 51, 2463–2470. CAS Google Scholar
Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Siemens (1995). SMART and SAINT. Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA. Google Scholar
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The title compound (I) was obtained as one of the two isomers of a Sharpless asymmetric dihydroxylation reaction of (1S)-1-((1R)-1-phenylethyl)-4-vinylpyrrolidin-2-one (Fava et al.1999). The major isomer from the reaction was recrystallized to give a pure sample for X-ray analysis. The molecular structure of (I) is shown in Fig. 1. The assignment of the absolute stereochemistry is based on the known stereochemistry of C7 (R). This leads to the absolute configuration at C10 and C13 as R.
The molecules of (I) in the crystal form one dimensional tapes along the b axis via hydrogen bonding between the carbonyl oxygen, O1 and the two alcohol moieties O2—H and O3—H. These assemble by interdigitative stacking of phenyl rings between tapes and further connection by C11—H11B···O3, C5—H5···O2 interactions between adjacent molecules to form sheets near the b-c plane, Fig. 2 (Table 1).