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The title compound, C18H19NO4, is the key synthetic intermediate in the preparation of [alpha],[alpha]-di­benzyl-[alpha]-amino acid (di­benzyl­glycine, Dbg), the disubstituted homologue of phenyl­alanine, following the di­alkyl­ation of ethyl nitro­acetate. The mol­ecule does not have its potential mirror symmetry in the crystal, with the two benzyl groups forming N-C-C-C torsion angles of 60.31 (13) and 79.89 (13)°.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270100014955/qa0411sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270100014955/qa0411Isup2.hkl
Contains datablock I

CCDC reference: 156207

Comment top

The ability of α,α-disubstituted-α-amino acids to modulate the chemical and physical properties of peptides (Olson et al., 1990) has given rise to an increased interest in their synthesis and subsequent incorporation into peptides (Trost & Arisa 1997; Dyker, 1997). One synthon of particular interest to the preparation of amino acids, as well as to other compounds of biological relevance, is the alkyl nitroacetates (Shipchandler, 1979). For the synthesis of mono- and disubstituted α-amino acids from these precursors, the ability to undergo electrophilic substitution reactions at the α-methylene of nitroacetate is of primary importance. However, the synthesis of the title compound, (I), representing dialkylation at this position, as opposed to competing O-alkylation, has previously required two separate synthetic steps to accomplish in moderate yield (Gogte et al., 1987). We have conducted the synthesis in one synthetic step, and herein the structure of the title compound is reported. Further structural comparisons with other α,α-disubstituted alkyl nitroacetates, as well as their conversion to novel prochiral α,α-disubstituted glycines, will be reported elsewhere (Fu et al., 2000). \scheme

The molecule potentially has mirror symmetry; however, it is crystallographically asymmetric, with benzyl groups forming torsion angles of the same sign with the nitro N atom, N1—C1—C5—C6 60.31 (13)° and N1—C1—C12—C13 79.89 (13)°. One is anti to the ester substituent [C2—C1—C5—C6 177.05 (10)°] while the other is more nearly syn [C2—C1—C12—C13 − 38.54 (14)°]. The phenyl rings thus form a dihedral angle of 74.04 (7)°.

Experimental top

Benzyl bromide (2.7 g, 15.8 mmol) was added to a mixture of ethyl nitroacetate (1.0 g. 7.5 mmol), tetrabutylammonium bromide (0.24 g, 0.75 mmol) and diisopropylethylamine (2.0 g, 15.8 mmol) dissolved in 5 ml of dry dimethylformamide. The reaction was stirred for 2 h, and the precipitated diisopropylethylammonium bromide salt was removed by filtration and washed with diethyl ether (100 ml). The resulting filtrate was washed with water (5 × 50 ml). The organic layer was dried over sodium sulfate, filtered, and the ether removed by evaporation at 273 K to provide a yellow oil (2.0 g, 88% crude yield). Silica-gel column chromatography with pentane/diethyl ether provided a white crystalline solid following removal of solvents (1.48 g, 63% yield). The compound was crystallized (in the dark under argon) from hot pentane by slow cooling.

Refinement top

H atoms were placed in calculated positions with C—H bond distances of 0.95 Å for phenyl, 0.99 Å for methylene and 0.98 Å for methyl, and thereafter treated as riding. A torsional parameter was refined for the methyl group. Uiso = 1.2Ueq of the attached C atom (1.5 for methyl groups).

Computing details top

Data collection: KappaCCD Software (Nonius, 1998); cell refinement: DENZO and SCALEPAK; data reduction: DENZO and SCALEPAK (Otwinowski & Minor, 1997); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); software used to prepare material for publication: SHELXL97.

Ethyl 2-Benzyl-2-nitro-3-phenylpropanoate top
Crystal data top
C18H19NO4F(000) = 664
Mr = 313.34Dx = 1.292 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 18.0850 (6) ÅCell parameters from 7336 reflections
b = 6.0670 (2) Åθ = 2.5–27.5°
c = 15.9830 (6) ŵ = 0.09 mm1
β = 113.280 (2)°T = 120 K
V = 1610.90 (10) Å3Lath, colourless
Z = 40.50 × 0.10 × 0.05 mm
Data collection top
KappaCCD (with Oxford Cryosystems Cryostream cooler)
diffractometer
2576 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.038
Graphite monochromatorθmax = 27.5°, θmin = 3.4°
ω scans with κ offsetsh = 2323
7336 measured reflectionsk = 77
3662 independent reflectionsl = 2020
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.039H-atom parameters constrained
wR(F2) = 0.094 w = 1/[σ2(Fo2) + (0.0388P)2 + 0.1307P]
where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max = 0.001
3662 reflectionsΔρmax = 0.27 e Å3
210 parametersΔρmin = 0.22 e Å3
0 restraintsExtinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0152 (17)
Crystal data top
C18H19NO4V = 1610.90 (10) Å3
Mr = 313.34Z = 4
Monoclinic, P21/cMo Kα radiation
a = 18.0850 (6) ŵ = 0.09 mm1
b = 6.0670 (2) ÅT = 120 K
c = 15.9830 (6) Å0.50 × 0.10 × 0.05 mm
β = 113.280 (2)°
Data collection top
KappaCCD (with Oxford Cryosystems Cryostream cooler)
diffractometer
2576 reflections with I > 2σ(I)
7336 measured reflectionsRint = 0.038
3662 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0390 restraints
wR(F2) = 0.094H-atom parameters constrained
S = 1.04Δρmax = 0.27 e Å3
3662 reflectionsΔρmin = 0.22 e Å3
210 parameters
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
O10.19690 (6)0.44747 (15)0.81248 (6)0.0344 (2)
O20.26130 (5)0.77258 (14)0.83315 (6)0.0267 (2)
O30.24154 (5)0.95503 (15)0.62506 (6)0.0336 (2)
O40.15004 (6)0.98732 (15)0.67960 (6)0.0331 (2)
N10.19922 (6)0.87969 (18)0.66197 (7)0.0252 (3)
C10.20260 (7)0.6323 (2)0.68295 (8)0.0211 (3)
C20.21764 (7)0.6072 (2)0.78347 (9)0.0238 (3)
C30.28908 (8)0.7509 (2)0.93147 (8)0.0317 (3)
H3A0.31840.61020.95220.038*
H3B0.24290.75420.95000.038*
C40.34387 (9)0.9424 (3)0.97160 (10)0.0430 (4)
H4A0.38740.94190.94970.064*
H4B0.36680.93071.03820.064*
H4C0.31331.08000.95330.064*
C50.11964 (7)0.5389 (2)0.62068 (8)0.0239 (3)
H5A0.11830.37950.63320.029*
H5B0.07760.61180.63590.029*
C60.10002 (7)0.5703 (2)0.52041 (8)0.0223 (3)
C70.06529 (7)0.7666 (2)0.47761 (8)0.0262 (3)
H70.05290.87840.51160.031*
C80.04857 (7)0.8012 (2)0.38620 (9)0.0299 (3)
H80.02500.93610.35800.036*
C90.06622 (7)0.6395 (2)0.33618 (9)0.0312 (3)
H90.05510.66350.27360.037*
C100.09997 (8)0.4427 (2)0.37699 (9)0.0319 (3)
H100.11170.33110.34240.038*
C110.11678 (7)0.4080 (2)0.46869 (9)0.0280 (3)
H110.13990.27230.49640.034*
C120.27142 (7)0.5200 (2)0.66547 (9)0.0237 (3)
H12A0.25920.36060.65600.028*
H12B0.27210.57960.60810.028*
C130.35516 (7)0.5457 (2)0.73967 (8)0.0248 (3)
C140.38473 (8)0.3836 (2)0.80657 (9)0.0308 (3)
H140.35280.25770.80450.037*
C150.46038 (8)0.4052 (3)0.87614 (10)0.0380 (4)
H150.47990.29440.92160.046*
C160.50754 (8)0.5872 (3)0.87959 (10)0.0387 (4)
H160.55910.60230.92770.046*
C170.47938 (8)0.7465 (3)0.81288 (9)0.0354 (3)
H170.51210.87040.81460.042*
C180.40359 (7)0.7269 (2)0.74330 (9)0.0287 (3)
H180.38460.83790.69780.034*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0439 (6)0.0298 (5)0.0319 (5)0.0065 (5)0.0174 (4)0.0046 (4)
O20.0314 (5)0.0255 (5)0.0224 (4)0.0006 (4)0.0099 (4)0.0000 (4)
O30.0358 (5)0.0265 (5)0.0388 (6)0.0061 (4)0.0150 (4)0.0070 (4)
O40.0420 (5)0.0239 (5)0.0333 (5)0.0089 (4)0.0147 (4)0.0008 (4)
N10.0292 (6)0.0193 (6)0.0237 (5)0.0007 (5)0.0068 (5)0.0005 (5)
C10.0255 (6)0.0139 (6)0.0245 (6)0.0006 (5)0.0104 (5)0.0017 (5)
C20.0240 (6)0.0216 (7)0.0275 (7)0.0026 (5)0.0120 (5)0.0011 (6)
C30.0342 (7)0.0390 (8)0.0208 (7)0.0020 (6)0.0096 (5)0.0014 (6)
C40.0398 (8)0.0600 (11)0.0279 (7)0.0124 (8)0.0121 (6)0.0082 (8)
C50.0233 (6)0.0194 (6)0.0289 (7)0.0013 (5)0.0104 (5)0.0008 (5)
C60.0183 (6)0.0204 (7)0.0274 (6)0.0026 (5)0.0082 (5)0.0014 (5)
C70.0253 (6)0.0229 (7)0.0291 (7)0.0015 (5)0.0093 (5)0.0020 (6)
C80.0279 (6)0.0267 (7)0.0296 (7)0.0002 (6)0.0057 (5)0.0036 (6)
C90.0273 (7)0.0399 (8)0.0250 (7)0.0072 (6)0.0088 (5)0.0031 (7)
C100.0272 (6)0.0352 (8)0.0334 (8)0.0021 (6)0.0121 (6)0.0102 (7)
C110.0255 (6)0.0219 (7)0.0340 (7)0.0012 (6)0.0091 (5)0.0026 (6)
C120.0256 (6)0.0196 (6)0.0266 (7)0.0002 (5)0.0111 (5)0.0006 (6)
C130.0255 (6)0.0260 (7)0.0253 (6)0.0026 (6)0.0127 (5)0.0013 (6)
C140.0301 (7)0.0307 (8)0.0340 (7)0.0032 (6)0.0153 (6)0.0030 (6)
C150.0354 (8)0.0474 (10)0.0305 (7)0.0102 (7)0.0123 (6)0.0077 (7)
C160.0257 (7)0.0562 (10)0.0304 (7)0.0020 (7)0.0072 (6)0.0049 (7)
C170.0281 (7)0.0412 (9)0.0378 (8)0.0074 (6)0.0140 (6)0.0077 (7)
C180.0268 (6)0.0301 (7)0.0310 (7)0.0012 (6)0.0134 (5)0.0002 (6)
Geometric parameters (Å, º) top
O1—C21.1966 (15)C8—C91.3802 (19)
O2—C21.3286 (15)C8—H80.9500
O2—C31.4544 (14)C9—C101.382 (2)
O3—N11.2245 (13)C9—H90.9500
O4—N11.2228 (13)C10—C111.3901 (19)
N1—C11.5336 (16)C10—H100.9500
C1—C21.5276 (17)C11—H110.9500
C1—C121.5384 (17)C12—C131.5181 (17)
C1—C51.5435 (16)C12—H12A0.9900
C3—C41.497 (2)C12—H12B0.9900
C3—H3A0.9900C13—C181.3924 (18)
C3—H3B0.9900C13—C141.3942 (18)
C4—H4A0.9800C14—C151.3867 (19)
C4—H4B0.9800C14—H140.9500
C4—H4C0.9800C15—C161.383 (2)
C5—C61.5102 (17)C15—H150.9500
C5—H5A0.9900C16—C171.379 (2)
C5—H5B0.9900C16—H160.9500
C6—C71.3934 (17)C17—C181.3873 (18)
C6—C111.3936 (18)C17—H170.9500
C7—C81.3859 (18)C18—H180.9500
C7—H70.9500
C2—O2—C3116.57 (10)C9—C8—C7119.93 (13)
O4—N1—O3124.18 (11)C9—C8—H8120.0
O4—N1—C1116.22 (10)C7—C8—H8120.0
O3—N1—C1119.48 (10)C8—C9—C10120.07 (12)
C2—C1—N1107.63 (10)C8—C9—H9120.0
C2—C1—C12109.04 (10)C10—C9—H9120.0
N1—C1—C12111.04 (10)C9—C10—C11120.01 (13)
C2—C1—C5111.42 (10)C9—C10—H10120.0
N1—C1—C5105.89 (9)C11—C10—H10120.0
C12—C1—C5111.73 (10)C10—C11—C6120.69 (12)
O1—C2—O2125.69 (12)C10—C11—H11119.7
O1—C2—C1122.39 (12)C6—C11—H11119.7
O2—C2—C1111.70 (10)C13—C12—C1116.21 (10)
O2—C3—C4106.28 (11)C13—C12—H12A108.2
O2—C3—H3A110.5C1—C12—H12A108.2
C4—C3—H3A110.5C13—C12—H12B108.2
O2—C3—H3B110.5C1—C12—H12B108.2
C4—C3—H3B110.5H12A—C12—H12B107.4
H3A—C3—H3B108.7C18—C13—C14118.73 (11)
C3—C4—H4A109.5C18—C13—C12122.03 (11)
C3—C4—H4B109.5C14—C13—C12119.24 (11)
H4A—C4—H4B109.5C15—C14—C13120.41 (14)
C3—C4—H4C109.5C15—C14—H14119.8
H4A—C4—H4C109.5C13—C14—H14119.8
H4B—C4—H4C109.5C16—C15—C14120.32 (14)
C6—C5—C1113.51 (10)C16—C15—H15119.8
C6—C5—H5A108.9C14—C15—H15119.8
C1—C5—H5A108.9C17—C16—C15119.69 (12)
C6—C5—H5B108.9C17—C16—H16120.2
C1—C5—H5B108.9C15—C16—H16120.2
H5A—C5—H5B107.7C16—C17—C18120.38 (14)
C7—C6—C11118.29 (12)C16—C17—H17119.8
C7—C6—C5120.00 (11)C18—C17—H17119.8
C11—C6—C5121.70 (11)C17—C18—C13120.46 (13)
C8—C7—C6121.01 (12)C17—C18—H18119.8
C8—C7—H7119.5C13—C18—H18119.8
C6—C7—H7119.5
O4—N1—C1—C255.88 (13)C5—C6—C7—C8178.40 (11)
O3—N1—C1—C2127.90 (11)C6—C7—C8—C90.15 (18)
O4—N1—C1—C12175.15 (10)C7—C8—C9—C100.46 (19)
O3—N1—C1—C128.62 (14)C8—C9—C10—C110.49 (18)
O4—N1—C1—C563.39 (13)C9—C10—C11—C60.08 (18)
O3—N1—C1—C5112.83 (11)C7—C6—C11—C100.67 (18)
C3—O2—C2—O13.02 (17)C5—C6—C11—C10178.42 (11)
C3—O2—C2—C1171.58 (10)C2—C1—C12—C1338.54 (14)
N1—C1—C2—O1154.00 (11)N1—C1—C12—C1379.89 (13)
C12—C1—C2—O185.46 (14)C5—C1—C12—C13162.13 (10)
C5—C1—C2—O138.32 (16)C1—C12—C13—C1886.16 (15)
N1—C1—C2—O231.19 (13)C1—C12—C13—C1493.66 (14)
C12—C1—C2—O289.35 (12)C18—C13—C14—C151.11 (19)
C5—C1—C2—O2146.87 (10)C12—C13—C14—C15178.72 (12)
C2—O2—C3—C4173.68 (11)C13—C14—C15—C160.4 (2)
C2—C1—C5—C6177.05 (10)C14—C15—C16—C170.7 (2)
N1—C1—C5—C660.31 (13)C15—C16—C17—C181.0 (2)
C12—C1—C5—C660.70 (13)C16—C17—C18—C130.3 (2)
C1—C5—C6—C785.52 (13)C14—C13—C18—C170.76 (19)
C1—C5—C6—C1193.56 (14)C12—C13—C18—C17179.06 (12)
C11—C6—C7—C80.71 (17)

Experimental details

Crystal data
Chemical formulaC18H19NO4
Mr313.34
Crystal system, space groupMonoclinic, P21/c
Temperature (K)120
a, b, c (Å)18.0850 (6), 6.0670 (2), 15.9830 (6)
β (°) 113.280 (2)
V3)1610.90 (10)
Z4
Radiation typeMo Kα
µ (mm1)0.09
Crystal size (mm)0.50 × 0.10 × 0.05
Data collection
DiffractometerKappaCCD (with Oxford Cryosystems Cryostream cooler)
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
7336, 3662, 2576
Rint0.038
(sin θ/λ)max1)0.650
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.039, 0.094, 1.04
No. of reflections3662
No. of parameters210
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.27, 0.22

Computer programs: KappaCCD Software (Nonius, 1998), DENZO and SCALEPAK (Otwinowski & Minor, 1997), SIR92 (Altomare et al., 1994), SHELXL97 (Sheldrick, 1997), SHELXL97.

 

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