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Acta Crystallogr Sect E Struct Rep Online. 2008 July 1; 64(Pt 7): o1330.
Published online 2008 June 25. doi:  10.1107/S1600536808018461
PMCID: PMC2961886

(S)-1,5-Dibenzyl-3-tert-butyl­imidazol­idin-4-one

Abstract

The title compound, C21H26N2O, was obtained as an unexpected by-product when attempting to prepare (S)-2-benzyl-N-tert-butyl-1,2,3,4-tetra­hydro­isoquinoline-3-carboxamide from (S)-2-benzyl­amino-N-tert-butyl-3-phenyl­propanamide and dimethoxy­methane. The mol­ecules are linked by weak C—H(...)O hydrogen bonds, generating linear chains parallel to the b axis. C—H(...)π inter­actions provide further stability for the crystal structure. The planes of the two phenyl rings make a dihedral angle of 84.1 (1)°. The absolute configuration was known from the starting material.

Related literature

For related literature, see: Allen et al. (1987 [triangle]); Pavel et al. (1993 [triangle]); Jin et al. 2005 [triangle].

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Object name is e-64-o1330-scheme1.jpg

Experimental

Crystal data

  • C21H26N2O
  • M r = 322.44
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1330-efi1.jpg
  • a = 9.4112 (6) Å
  • b = 11.4713 (7) Å
  • c = 17.0556 (11) Å
  • V = 1841.3 (2) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.07 mm−1
  • T = 173 (2) K
  • 0.62 × 0.45 × 0.23 mm

Data collection

  • Bruker APEX CCD diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2001 [triangle]) T min = 0.957, T max = 0.984
  • 8034 measured reflections
  • 2047 independent reflections
  • 1824 reflections with I > 2σ(I)
  • R int = 0.023

Refinement

  • R[F 2 > 2σ(F 2)] = 0.042
  • wR(F 2) = 0.107
  • S = 1.00
  • 2047 reflections
  • 217 parameters
  • H-atom parameters constrained
  • Δρmax = 0.34 e Å−3
  • Δρmin = −0.18 e Å−3

Data collection: SMART (Bruker, 2001 [triangle]); cell refinement: SAINT (Bruker, 2001 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEPIII (Farrugia, 1997 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808018461/bt2725sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808018461/bt2725Isup2.hkl

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

Acknowledgments

The authors acknowledge the Natural Science Foundation of Fujian Province of China (No. U0650024), Xiamen Science Foundation (No.3502Z20055019) and NFFTBS (No. J0630429) for financial support. We also thank Mr Z.-B. Wei and Mr T.-B. Wen for technical assistance.

supplementary crystallographic information

Comment

In our studies on the synthesis of (S)—N-tert-butyl-tetrahydroisoquinoline- 3-carboxamide, a key intermediate for the synthesis of Nelfinavir and Saquinavir, two of the most clinically efficacious anti-AIDS drugs, we attempted to prepare (S)-2-benzyl-N-tert-butyl-1,2,3,4-tetrahydroisoquinoline- 3-carboxamide from (S)-2-(benzylamino)-N-tert-butyl-3 -phenylpropanamide and dimethoxymethane. During this experiment, the title compound, (I), was isolated unexpectedly.

The two planes of phenyl rings make a dihedral angle of 84.1 (1)° (Fig. 1). The absolute configuration (S) of the stereocentre C5 remains unchanged during the synthetic procedure. An X-ray crystal structure determination of the molecular structure of compound (I) was carried out to determine its conformation. The bond lengths are within normal ranges (Allen et al., 1987).

The packing is shown in Fig. 2. The occurrence of weak C—H···O hydrogen bond interactions leads to the formation of linear chains parallel to the b axis. The packing is further stabilized by C—H···π interactions (Fig. 2) with typical geometry (Pavel et al., 1993).

Experimental

The title compound was prepared by a method based on one described by Jin et al. (2005). To a solution of (S)-2-(benzylamino)-N-tert-butyl- 3-phenylpropanamide (11.8 g, 38.1 mmol) in dichloromethane (400 ml) was added dropwise boron trifluoride etherate (13.5 ml, 79.6 mmol) and dimethoxymethane (6.02 g, 79.1 mmol). The mixture was heated to reflux for 48 h. The reaction was quenched by addition of water (90 ml). The solution was adjusted to pH 8 with a 27% aqueous ammonia solution. The organic layer was separated, and the aqueous phase was extracted with dichloromethane. The combined organic phases were washed with brine and dried over Na2SO4. After filtration and evaporation of the solvents under reduced pressure, the residue was flash chromatographic purification on silica gel (ethyl acetate / petroleum ether = 1 / 4) yielded the product as a white solid. Single crystals were obtained by slow evaporation of a mixture of petroleum ether / dichloromethane solution.

Refinement

In the absence of anomalous scatterers, Friedel pairs were merged. The absolute configuration was known from the starting material. The hydrogen atoms were positioned geometrically (C—H = 0.93, 0.98, 0.97 or 0.96Å for phenyl, tertiary, methylene or methyl H atoms respectively) and were included in the refinement in the riding model approximation. The displacement parameters of methyl H atoms were set to 1.5Ueq(C), while those of other H atoms were set to 1.2Ueq(C).

Figures

Fig. 1.
The molecular structure of (I) with the atom-labeling scheme, showing 50% probability displacement ellipsoids. H atoms are drawn as spheres of arbitrary radius.
Fig. 2.
The packing of the molecules, viewed down the a axis. C—H···π and hydrogen bonds interactions are shown as dashed lines. Cg is the centroid of the C7 / C12 phenyl ring.

Crystal data

C21H26N2OF000 = 696
Mr = 322.44Dx = 1.163 Mg m3
Orthorhombic, P212121Mo Kα radiation λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 5367 reflections
a = 9.4112 (6) Åθ = 2.8–32.4º
b = 11.4713 (7) ŵ = 0.07 mm1
c = 17.0556 (11) ÅT = 173 (2) K
V = 1841.3 (2) Å3Block, colorless
Z = 40.62 × 0.45 × 0.23 mm

Data collection

Bruker APEX CCD diffractometer2047 independent reflections
Radiation source: fine-focus sealed tube1824 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.023
Detector resolution: 16.1903 pixels mm-1θmax = 26.0º
T = 173(2) Kθmin = 2.8º
[var phi] and ω scansh = −11→11
Absorption correction: multi-scan(SADABS; Bruker, 2001)k = −11→14
Tmin = 0.957, Tmax = 0.984l = −20→21
8034 measured reflections

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.042H-atom parameters constrained
wR(F2) = 0.107  w = 1/[σ2(Fo2) + (0.0673P)2 + 0.3582P] where P = (Fo2 + 2Fc2)/3
S = 1.00(Δ/σ)max < 0.001
2047 reflectionsΔρmax = 0.34 e Å3
217 parametersΔρmin = −0.18 e Å3
Primary atom site location: structure-invariant direct methodsExtinction correction: none

Special details

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)

xyzUiso*/Ueq
N10.3052 (2)0.09221 (18)0.72137 (12)0.0250 (5)
C20.3096 (3)0.0518 (2)0.80219 (15)0.0286 (6)
H2A0.3427−0.03000.80540.034*
H2B0.21520.05810.82740.034*
N30.4114 (2)0.1312 (2)0.83816 (13)0.0310 (5)
O40.6042 (2)0.2352 (2)0.79357 (14)0.0554 (7)
C40.4998 (3)0.1736 (2)0.78380 (18)0.0343 (6)
C50.4499 (3)0.1293 (2)0.70449 (16)0.0296 (6)
H50.50770.05960.68960.036*
C60.2517 (3)0.0043 (2)0.66686 (16)0.0302 (6)
H6A0.3094−0.06740.67190.036*
H6B0.26200.03340.61250.036*
C70.0978 (3)−0.0245 (2)0.68211 (14)0.0273 (6)
C80.0523 (3)−0.1392 (2)0.68251 (17)0.0337 (6)
H80.1188−0.20040.67450.040*
C9−0.0903 (3)−0.1651 (3)0.69453 (19)0.0424 (7)
H9−0.1208−0.24410.69400.051*
C10−0.1867 (3)−0.0786 (3)0.7070 (2)0.0443 (8)
H10−0.2840−0.09710.71530.053*
C11−0.1422 (3)0.0367 (3)0.7075 (2)0.0458 (8)
H11−0.20870.09750.71660.055*
C12−0.0008 (3)0.0628 (2)0.69456 (18)0.0362 (7)
H120.02910.14190.69420.043*
C130.4632 (4)0.2208 (3)0.64056 (17)0.0399 (7)
H13A0.38220.27530.64570.048*
H13B0.55100.26600.65040.048*
C140.4673 (3)0.1777 (2)0.55702 (17)0.0326 (6)
C150.3770 (4)0.2246 (3)0.5011 (2)0.0469 (8)
H150.30860.28130.51610.056*
C160.3856 (4)0.1894 (3)0.4231 (2)0.0553 (10)
H160.32380.22290.38530.066*
C170.4815 (4)0.1078 (3)0.40063 (19)0.0508 (9)
H170.48820.08520.34720.061*
C180.5691 (3)0.0578 (3)0.45596 (19)0.0476 (8)
H180.6343−0.00130.44090.057*
C190.5622 (3)0.0934 (3)0.53324 (18)0.0399 (7)
H190.62420.05910.57070.048*
C200.4334 (3)0.1408 (3)0.92442 (17)0.0382 (7)
C210.5676 (6)0.0773 (5)0.9454 (3)0.0904 (15)
H21A0.5591−0.00480.93010.109*
H21B0.58350.08251.00200.109*
H21C0.64780.11270.91760.109*
C220.3043 (5)0.0931 (5)0.9661 (2)0.0855 (14)
H22A0.29310.01020.95350.103*
H22B0.21970.13590.94900.103*
H22C0.31630.10221.02290.103*
C230.4439 (5)0.2670 (3)0.9470 (2)0.0604 (10)
H23A0.52710.30190.92160.091*
H23B0.45360.27351.00400.091*
H23C0.35790.30810.93000.091*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N10.0249 (10)0.0266 (10)0.0235 (11)−0.0031 (9)0.0000 (9)−0.0017 (9)
C20.0307 (13)0.0274 (12)0.0277 (13)−0.0071 (11)−0.0031 (11)0.0001 (11)
N30.0279 (11)0.0358 (12)0.0293 (12)−0.0077 (10)−0.0043 (9)−0.0024 (10)
O40.0406 (12)0.0721 (16)0.0535 (14)−0.0296 (12)0.0094 (11)−0.0233 (12)
C40.0277 (12)0.0354 (14)0.0397 (15)−0.0057 (12)0.0037 (13)−0.0089 (12)
C50.0281 (13)0.0283 (12)0.0324 (14)−0.0034 (11)0.0060 (12)−0.0057 (11)
C60.0331 (13)0.0300 (13)0.0275 (13)−0.0049 (12)0.0008 (11)−0.0073 (11)
C70.0325 (14)0.0295 (12)0.0198 (11)−0.0056 (11)−0.0042 (11)0.0003 (10)
C80.0406 (15)0.0293 (13)0.0314 (14)−0.0049 (12)−0.0028 (12)0.0004 (12)
C90.0476 (17)0.0374 (15)0.0422 (17)−0.0168 (14)−0.0120 (14)0.0079 (13)
C100.0304 (14)0.0547 (19)0.0479 (18)−0.0117 (14)−0.0080 (14)0.0090 (15)
C110.0316 (15)0.0472 (18)0.059 (2)0.0009 (13)−0.0099 (15)0.0036 (16)
C120.0336 (14)0.0299 (13)0.0450 (16)−0.0025 (12)−0.0067 (13)−0.0008 (13)
C130.0526 (18)0.0293 (13)0.0378 (17)−0.0078 (14)0.0140 (14)−0.0011 (12)
C140.0351 (14)0.0285 (13)0.0342 (15)−0.0089 (12)0.0063 (12)0.0038 (11)
C150.0500 (19)0.0334 (16)0.057 (2)0.0005 (15)−0.0022 (16)0.0135 (16)
C160.059 (2)0.060 (2)0.047 (2)−0.0115 (19)−0.0159 (18)0.0226 (17)
C170.052 (2)0.067 (2)0.0334 (16)−0.0305 (19)0.0027 (15)0.0044 (15)
C180.0399 (17)0.061 (2)0.0414 (17)−0.0065 (16)0.0117 (15)−0.0079 (16)
C190.0341 (15)0.0501 (17)0.0355 (16)−0.0011 (14)0.0020 (13)0.0011 (14)
C200.0396 (15)0.0439 (17)0.0311 (15)−0.0076 (14)−0.0108 (12)0.0003 (13)
C210.103 (3)0.095 (3)0.073 (3)0.036 (3)−0.038 (2)−0.012 (2)
C220.098 (3)0.120 (3)0.0391 (18)−0.052 (3)−0.003 (2)−0.001 (2)
C230.084 (3)0.058 (2)0.0385 (19)−0.011 (2)0.003 (2)−0.0113 (16)

Geometric parameters (Å, °)

N1—C21.455 (3)C13—C141.508 (4)
N1—C51.455 (3)C13—H13A0.9900
N1—C61.461 (3)C13—H13B0.9900
C2—N31.457 (3)C14—C191.378 (4)
C2—H2A0.9900C14—C151.387 (4)
C2—H2B0.9900C15—C161.392 (5)
N3—C41.336 (4)C15—H150.9500
N3—C201.490 (4)C16—C171.355 (5)
O4—C41.222 (3)C16—H160.9500
C4—C51.519 (4)C17—C181.378 (5)
C5—C131.519 (4)C17—H170.9500
C5—H51.0000C18—C191.381 (5)
C6—C71.508 (4)C18—H180.9500
C6—H6A0.9900C19—H190.9500
C6—H6B0.9900C20—C211.501 (5)
C7—C121.381 (4)C20—C231.502 (5)
C7—C81.384 (4)C20—C221.510 (5)
C8—C91.390 (4)C21—H21A0.9800
C8—H80.9500C21—H21B0.9800
C9—C101.362 (4)C21—H21C0.9800
C9—H90.9500C22—H22A0.9800
C10—C111.388 (5)C22—H22B0.9800
C10—H100.9500C22—H22C0.9800
C11—C121.382 (4)C23—H23A0.9800
C11—H110.9500C23—H23B0.9800
C12—H120.9500C23—H23C0.9800
C2—N1—C5104.7 (2)C5—C13—H13A108.0
C2—N1—C6113.1 (2)C14—C13—H13B108.0
C5—N1—C6113.5 (2)C5—C13—H13B108.0
N1—C2—N3102.62 (19)H13A—C13—H13B107.3
N1—C2—H2A111.2C19—C14—C15117.9 (3)
N3—C2—H2A111.2C19—C14—C13121.6 (3)
N1—C2—H2B111.2C15—C14—C13120.5 (3)
N3—C2—H2B111.2C14—C15—C16120.6 (3)
H2A—C2—H2B109.2C14—C15—H15119.7
C4—N3—C2110.1 (2)C16—C15—H15119.7
C4—N3—C20124.9 (2)C17—C16—C15120.7 (3)
C2—N3—C20123.6 (2)C17—C16—H16119.7
O4—C4—N3128.0 (3)C15—C16—H16119.7
O4—C4—C5124.3 (3)C16—C17—C18119.4 (3)
N3—C4—C5107.7 (2)C16—C17—H17120.3
N1—C5—C13114.9 (2)C18—C17—H17120.3
N1—C5—C4102.2 (2)C17—C18—C19120.2 (3)
C13—C5—C4112.5 (2)C17—C18—H18119.9
N1—C5—H5109.0C19—C18—H18119.9
C13—C5—H5109.0C14—C19—C18121.2 (3)
C4—C5—H5109.0C14—C19—H19119.4
N1—C6—C7111.9 (2)C18—C19—H19119.4
N1—C6—H6A109.2N3—C20—C21108.4 (3)
C7—C6—H6A109.2N3—C20—C23109.5 (3)
N1—C6—H6B109.2C21—C20—C23110.6 (3)
C7—C6—H6B109.2N3—C20—C22109.1 (3)
H6A—C6—H6B107.9C21—C20—C22112.9 (4)
C12—C7—C8118.7 (3)C23—C20—C22106.4 (3)
C12—C7—C6120.9 (2)C20—C21—H21A109.5
C8—C7—C6120.4 (3)C20—C21—H21B109.5
C7—C8—C9120.2 (3)H21A—C21—H21B109.5
C7—C8—H8119.9C20—C21—H21C109.4
C9—C8—H8119.9H21A—C21—H21C109.5
C10—C9—C8120.7 (3)H21B—C21—H21C109.5
C10—C9—H9119.6C20—C22—H22A109.5
C8—C9—H9119.6C20—C22—H22B109.4
C9—C10—C11119.6 (3)H22A—C22—H22B109.5
C9—C10—H10120.2C20—C22—H22C109.5
C11—C10—H10120.2H22A—C22—H22C109.5
C12—C11—C10119.8 (3)H22B—C22—H22C109.5
C12—C11—H11120.1C20—C23—H23A109.5
C10—C11—H11120.1C20—C23—H23B109.5
C7—C12—C11121.0 (3)H23A—C23—H23B109.5
C7—C12—H12119.5C20—C23—H23C109.5
C11—C12—H12119.5H23A—C23—H23C109.5
C14—C13—C5117.0 (2)H23B—C23—H23C109.5
C14—C13—H13A108.0
C5—N1—C2—N335.3 (3)C8—C9—C10—C110.2 (5)
C6—N1—C2—N3159.4 (2)C9—C10—C11—C120.6 (5)
N1—C2—N3—C4−25.0 (3)C8—C7—C12—C110.2 (4)
N1—C2—N3—C20168.0 (2)C6—C7—C12—C11179.1 (3)
C2—N3—C4—O4−174.1 (3)C10—C11—C12—C7−0.8 (5)
C20—N3—C4—O4−7.3 (5)N1—C5—C13—C14−84.6 (3)
C2—N3—C4—C54.8 (3)C4—C5—C13—C14159.1 (3)
C20—N3—C4—C5171.5 (3)C5—C13—C14—C19−52.8 (4)
C2—N1—C5—C13−154.4 (2)C5—C13—C14—C15128.8 (3)
C6—N1—C5—C1381.8 (3)C19—C14—C15—C16−1.8 (5)
C2—N1—C5—C4−32.3 (3)C13—C14—C15—C16176.6 (3)
C6—N1—C5—C4−156.1 (2)C14—C15—C16—C170.7 (5)
O4—C4—C5—N1−163.8 (3)C15—C16—C17—C181.2 (5)
N3—C4—C5—N117.3 (3)C16—C17—C18—C19−2.0 (5)
O4—C4—C5—C13−40.1 (4)C15—C14—C19—C181.0 (4)
N3—C4—C5—C13141.0 (2)C13—C14—C19—C18−177.4 (3)
C2—N1—C6—C765.6 (3)C17—C18—C19—C140.9 (5)
C5—N1—C6—C7−175.3 (2)C4—N3—C20—C21−62.2 (4)
N1—C6—C7—C1245.6 (3)C2—N3—C20—C21102.8 (4)
N1—C6—C7—C8−135.5 (3)C4—N3—C20—C2358.5 (4)
C12—C7—C8—C90.6 (4)C2—N3—C20—C23−136.5 (3)
C6—C7—C8—C9−178.3 (3)C4—N3—C20—C22174.5 (3)
C7—C8—C9—C10−0.8 (5)C2—N3—C20—C22−20.5 (4)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C6—H6A···O4i0.992.483.439 (4)164
C17—H17···Cgii0.952.683.621 (4)169

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BT2725).

References

  • Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19.
  • Bruker (2001). SAINT, SMART and SADABS Bruker AXS Inc., Madison, Wisconsin, USA.
  • Farrugia, L. J. (1997). J. Appl. Cryst.30, 565.
  • Jin, L. R., Huang, S. J. & Zhang, F. J. (2005). China Patent 1 562 974.
  • Pavel, H., Heinrich, L. S. & Edward, W. S. (1993). J. Am. Chem. Soc.116, 3500–3506.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]

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