Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536802020974/cm6021sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536802020974/cm6021Isup2.hkl |
CCDC reference: 190945
Glassware was flame dried under an argon atmosphere and allowed to cool. (S)-2-Aminobutyric acid (5 g, 48.5 mmol) was dissolved in a cold (273 K) solution of dioxane (50 ml) and 1M aqueous NaOH (100 ml). To the flask di-tert-butyl-dicarbonate (12.8 g, 59.0 mmol) was added in portions under stirring. After stirring for two days, the solvent was removed by evaporation under reduced pressure. The clear solution was acidified with 1M KHSO4 to a pH of 2–3 (white precipitate occurs) and then cold saturated NaHCO3 was added carefully to neutralize the mixture, which was then extracted with ethyl acetate several times. The collected organic phases were dried over Na2SO4, filtered and concentrated in vacuo to yield a colourless oil, which was used without further purification. The oil was dissolved in anhyd. dichloromethane (200 ml) and cooled to 250 K. N,O-Dimethylhydroxylamine hydrochloride (4.86 g, 49.8 mmol) and N-methyl morpholine (5.5 ml, 49.8 mmol) were added in one portion. After stirring for 10 min, N-(3-dimethylaminopropyl)-N'-ethyl carbodiimide hydrochloride (9.55 g, 49.8 mmol) was dissolved in the clear solution and stirring continued for 1 h; during which time a white solid precipitated. The aqueous phase was extracted with dichloromethane and the collected organic phases washed with saturated NaHCO3 and then dried over Na2SO4, filtered and evaporated under reduced pressure to yield a colourless solid. The product was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 2:1) to give colourless crystals (yield: 7.01 g, 58.8%) which were suitable for X-ray analysis.
The absolute configuration of the title compound could not be determined from the X-ray data but was fixed by the absolute stereochemistry of the starting material, (S)-2-aminobutyric acid. The position of the amide H atom was determined from a difference Fourier map and its coordinates refined freely, with the isotropic displacement parameter constrained to U(H) = 1.5 Ueq (N). All remaining H atoms were treated as riding, with C—H = 0.98–1.00 Å, and Uiso(H) = 1.2 Ueq (CH, CH2) and 1.5 Ueq (CH3).
Data collection: COLLECT (Nonius, 1997–2000); cell refinement: HKL SCALEPACK (Otwinowski & Minor 1997); data reduction: HKL DENZO (Otwinowski & Minor 1997) and SCALEPACK; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL-Plus (Sheldrick, 1991); software used to prepare material for publication: SHELXL97.
C11H22N2O4 | Dx = 1.194 Mg m−3 |
Mr = 246.31 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, P212121 | Cell parameters from 19365 reflections |
a = 6.6315 (1) Å | θ = 1–28° |
b = 9.8478 (2) Å | µ = 0.09 mm−1 |
c = 20.9769 (5) Å | T = 123 K |
V = 1369.91 (5) Å3 | Prisms, colourless |
Z = 4 | 0.40 × 0.20 × 0.10 mm |
F(000) = 536 |
Nonius Kappa-CCD diffractometer | 3020 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.032 |
Graphite monochromator | θmax = 28.3°, θmin = 2.8° |
ϕ and ω scans | h = −8→8 |
19820 measured reflections | k = −13→13 |
3362 independent reflections | l = −27→27 |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.034 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.090 | w = 1/[σ2(Fo2) + (0.0542P)2 + 0.0843P] where P = (Fo2 + 2Fc2)/3 |
S = 1.07 | (Δ/σ)max = 0.001 |
3362 reflections | Δρmax = 0.20 e Å−3 |
159 parameters | Δρmin = −0.29 e Å−3 |
1 restraint | Absolute structure: Flack H D (1983), Acta Cryst. A39, 876-881 |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0.2 (8) |
C11H22N2O4 | V = 1369.91 (5) Å3 |
Mr = 246.31 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 6.6315 (1) Å | µ = 0.09 mm−1 |
b = 9.8478 (2) Å | T = 123 K |
c = 20.9769 (5) Å | 0.40 × 0.20 × 0.10 mm |
Nonius Kappa-CCD diffractometer | 3020 reflections with I > 2σ(I) |
19820 measured reflections | Rint = 0.032 |
3362 independent reflections |
R[F2 > 2σ(F2)] = 0.034 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.090 | Δρmax = 0.20 e Å−3 |
S = 1.07 | Δρmin = −0.29 e Å−3 |
3362 reflections | Absolute structure: Flack H D (1983), Acta Cryst. A39, 876-881 |
159 parameters | Absolute structure parameter: 0.2 (8) |
1 restraint |
Experimental. dx = 39.740 (6) mm; mos.= 0.446 (1) 2 x 60 s; 1 °.; 579 frams TLC: 2:1 cyclohexane-ethyl acetate, Rf: 0.36; αD: +4.1 ° (c = 0.66; CHCl3); m.p.: 334 K; 1H-NMR (400 MHz, CDCl3): δ 0.87 (t, J = 7.0 Hz, 3H; CH3), 1.36 (s, 9H; C(CH3)3), 1.50 (m, 1H; CH2), 1.69 (m, 1H; CH2), 3.13 (s, 3H; CH3), 3.70 (s, 3H; CH3), 4.55 (m, 1H; CHN), 5.33 (d, J = 8.9 Hz, 1H; NH); 13C-NMR (100 MHz, CDCl3): δ 9.66 (CH3), 25.74 (CH2), 28.33 (C(CH3)3), 31.76 (NCH3), 51.35 (OCH3), 61.33 (CHN), 78.99 (C(CH3)3), 155.41 (NCO), 172.91 (CON); elemental analyses (%): C11H22N2O4 (246.31): calc.: C 53.64, H 9.00, N 11.37; found: C 53.76, H 9.22, N 11.26; FAB-MS (3-Nitrobenzoic acid): 269.1 (M+Na)+, 247.2 (M+H)+. |
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 | ||
C1 | 0.3483 (2) | 0.80113 (13) | 0.56443 (7) | 0.0360 (3) | |
H1A | 0.4701 | 0.8553 | 0.5718 | 0.054* | |
H1B | 0.2301 | 0.8512 | 0.5797 | 0.054* | |
H1C | 0.3339 | 0.7832 | 0.5187 | 0.054* | |
O2 | 0.36423 (13) | 0.67448 (9) | 0.59820 (4) | 0.02711 (19) | |
N3 | 0.53544 (16) | 0.60343 (11) | 0.57723 (5) | 0.0252 (2) | |
C31 | 0.7155 (2) | 0.62789 (14) | 0.61501 (6) | 0.0300 (3) | |
H31A | 0.6873 | 0.6077 | 0.6599 | 0.045* | |
H31B | 0.7557 | 0.7232 | 0.6108 | 0.045* | |
H31C | 0.8248 | 0.5693 | 0.5999 | 0.045* | |
C4 | 0.50610 (17) | 0.48948 (12) | 0.54203 (5) | 0.0202 (2) | |
O41 | 0.64865 (13) | 0.41643 (8) | 0.52818 (4) | 0.02516 (19) | |
C5 | 0.28824 (19) | 0.45748 (12) | 0.52326 (5) | 0.0226 (2) | |
H5 | 0.2158 | 0.5448 | 0.5150 | 0.027* | |
C51 | 0.18403 (18) | 0.38390 (14) | 0.57853 (6) | 0.0286 (3) | |
H51A | 0.1723 | 0.4474 | 0.6149 | 0.034* | |
H51B | 0.0457 | 0.3590 | 0.5651 | 0.034* | |
C52 | 0.2923 (2) | 0.25629 (15) | 0.60096 (6) | 0.0343 (3) | |
H52A | 0.2172 | 0.2154 | 0.6363 | 0.051* | |
H52B | 0.4285 | 0.2800 | 0.6153 | 0.051* | |
H52C | 0.3011 | 0.1913 | 0.5657 | 0.051* | |
N6 | 0.28131 (16) | 0.37545 (10) | 0.46600 (4) | 0.0223 (2) | |
H6 | 0.239 (2) | 0.2936 (14) | 0.4662 (7) | 0.034* | |
C7 | 0.31868 (17) | 0.43294 (11) | 0.40907 (5) | 0.0214 (2) | |
O71 | 0.37025 (16) | 0.55113 (9) | 0.40194 (4) | 0.0331 (2) | |
O8 | 0.29209 (14) | 0.34248 (8) | 0.36164 (4) | 0.02320 (18) | |
C9 | 0.28089 (19) | 0.38672 (13) | 0.29463 (5) | 0.0270 (3) | |
C91 | 0.1209 (3) | 0.49283 (17) | 0.28593 (7) | 0.0466 (4) | |
H91A | −0.0083 | 0.4579 | 0.3015 | 0.070* | |
H91B | 0.1091 | 0.5155 | 0.2406 | 0.070* | |
H91C | 0.1576 | 0.5745 | 0.3100 | 0.070* | |
C92 | 0.4827 (3) | 0.4343 (3) | 0.27165 (8) | 0.0734 (7) | |
H92A | 0.5826 | 0.3622 | 0.2781 | 0.110* | |
H92B | 0.5231 | 0.5152 | 0.2956 | 0.110* | |
H92C | 0.4745 | 0.4564 | 0.2262 | 0.110* | |
C93 | 0.2141 (5) | 0.25698 (17) | 0.26163 (7) | 0.0682 (7) | |
H93A | 0.0814 | 0.2299 | 0.2777 | 0.102* | |
H93B | 0.3119 | 0.1847 | 0.2703 | 0.102* | |
H93C | 0.2059 | 0.2726 | 0.2156 | 0.102* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0425 (8) | 0.0290 (6) | 0.0365 (7) | 0.0108 (6) | −0.0025 (6) | −0.0019 (5) |
O2 | 0.0285 (4) | 0.0272 (4) | 0.0256 (4) | 0.0052 (4) | 0.0014 (4) | −0.0070 (3) |
N3 | 0.0222 (5) | 0.0257 (5) | 0.0277 (5) | 0.0028 (4) | −0.0044 (4) | −0.0080 (4) |
C31 | 0.0296 (6) | 0.0299 (6) | 0.0305 (6) | −0.0030 (5) | −0.0082 (5) | −0.0026 (5) |
C4 | 0.0212 (6) | 0.0205 (5) | 0.0188 (5) | 0.0000 (4) | 0.0004 (4) | 0.0004 (4) |
O41 | 0.0224 (4) | 0.0235 (4) | 0.0296 (4) | 0.0024 (3) | 0.0017 (3) | −0.0025 (3) |
C5 | 0.0225 (5) | 0.0247 (5) | 0.0205 (5) | 0.0031 (5) | −0.0036 (4) | −0.0055 (4) |
C51 | 0.0190 (6) | 0.0425 (7) | 0.0244 (6) | −0.0042 (5) | 0.0018 (4) | −0.0056 (5) |
C52 | 0.0296 (6) | 0.0480 (8) | 0.0251 (6) | −0.0103 (6) | −0.0013 (5) | 0.0092 (6) |
N6 | 0.0276 (5) | 0.0195 (4) | 0.0199 (5) | −0.0030 (4) | −0.0032 (4) | −0.0022 (4) |
C7 | 0.0204 (5) | 0.0203 (5) | 0.0236 (5) | 0.0001 (4) | −0.0043 (4) | −0.0004 (4) |
O71 | 0.0438 (5) | 0.0228 (4) | 0.0326 (5) | −0.0084 (4) | −0.0089 (4) | 0.0033 (4) |
O8 | 0.0312 (4) | 0.0213 (4) | 0.0172 (4) | −0.0007 (3) | −0.0007 (3) | 0.0004 (3) |
C9 | 0.0311 (6) | 0.0316 (6) | 0.0183 (5) | −0.0004 (5) | −0.0016 (5) | 0.0038 (5) |
C91 | 0.0512 (9) | 0.0561 (9) | 0.0324 (7) | 0.0188 (8) | −0.0135 (7) | 0.0041 (7) |
C92 | 0.0359 (9) | 0.153 (2) | 0.0309 (8) | −0.0110 (12) | 0.0002 (7) | 0.0390 (11) |
C93 | 0.143 (2) | 0.0413 (8) | 0.0207 (7) | 0.0037 (11) | −0.0102 (10) | −0.0066 (6) |
C1—O2 | 1.4382 (16) | C52—H52B | 0.9800 |
C1—H1A | 0.9800 | C52—H52C | 0.9800 |
C1—H1B | 0.9800 | N6—C7 | 1.3445 (15) |
C1—H1C | 0.9800 | N6—H6 | 0.854 (13) |
O2—N3 | 1.4043 (13) | C7—O71 | 1.2223 (14) |
N3—C4 | 1.3572 (15) | C7—O8 | 1.3471 (13) |
N3—C31 | 1.4532 (16) | O8—C9 | 1.4735 (13) |
C31—H31A | 0.9800 | C9—C92 | 1.498 (2) |
C31—H31B | 0.9800 | C9—C91 | 1.500 (2) |
C31—H31C | 0.9800 | C9—C93 | 1.519 (2) |
C4—O41 | 1.2229 (14) | C91—H91A | 0.9800 |
C4—C5 | 1.5302 (17) | C91—H91B | 0.9800 |
C5—N6 | 1.4483 (14) | C91—H91C | 0.9800 |
C5—C51 | 1.5319 (17) | C92—H92A | 0.9800 |
C5—H5 | 1.0000 | C92—H92B | 0.9800 |
C51—C52 | 1.522 (2) | C92—H92C | 0.9800 |
C51—H51A | 0.9900 | C93—H93A | 0.9800 |
C51—H51B | 0.9900 | C93—H93B | 0.9800 |
C52—H52A | 0.9800 | C93—H93C | 0.9800 |
O2—C1—H1A | 109.5 | C51—C52—H52C | 109.5 |
O2—C1—H1B | 109.5 | H52A—C52—H52C | 109.5 |
H1A—C1—H1B | 109.5 | H52B—C52—H52C | 109.5 |
O2—C1—H1C | 109.5 | C7—N6—C5 | 119.73 (10) |
H1A—C1—H1C | 109.5 | C7—N6—H6 | 117.5 (11) |
H1B—C1—H1C | 109.5 | C5—N6—H6 | 122.2 (11) |
N3—O2—C1 | 109.70 (10) | O71—C7—N6 | 124.15 (11) |
C4—N3—O2 | 117.80 (9) | O71—C7—O8 | 125.16 (11) |
C4—N3—C31 | 123.47 (10) | N6—C7—O8 | 110.69 (9) |
O2—N3—C31 | 114.25 (9) | C7—O8—C9 | 121.04 (9) |
N3—C31—H31A | 109.5 | O8—C9—C92 | 110.76 (11) |
N3—C31—H31B | 109.5 | O8—C9—C91 | 110.95 (11) |
H31A—C31—H31B | 109.5 | C92—C9—C91 | 112.02 (14) |
N3—C31—H31C | 109.5 | O8—C9—C93 | 101.58 (10) |
H31A—C31—H31C | 109.5 | C92—C9—C93 | 112.13 (18) |
H31B—C31—H31C | 109.5 | C91—C9—C93 | 108.92 (14) |
O41—C4—N3 | 120.31 (11) | C9—C91—H91A | 109.5 |
O41—C4—C5 | 123.20 (10) | C9—C91—H91B | 109.5 |
N3—C4—C5 | 116.46 (10) | H91A—C91—H91B | 109.5 |
N6—C5—C4 | 110.99 (10) | C9—C91—H91C | 109.5 |
N6—C5—C51 | 110.47 (10) | H91A—C91—H91C | 109.5 |
C4—C5—C51 | 109.18 (9) | H91B—C91—H91C | 109.5 |
N6—C5—H5 | 108.7 | C9—C92—H92A | 109.5 |
C4—C5—H5 | 108.7 | C9—C92—H92B | 109.5 |
C51—C5—H5 | 108.7 | H92A—C92—H92B | 109.5 |
C52—C51—C5 | 114.30 (10) | C9—C92—H92C | 109.5 |
C52—C51—H51A | 108.7 | H92A—C92—H92C | 109.5 |
C5—C51—H51A | 108.7 | H92B—C92—H92C | 109.5 |
C52—C51—H51B | 108.7 | C9—C93—H93A | 109.5 |
C5—C51—H51B | 108.7 | C9—C93—H93B | 109.5 |
H51A—C51—H51B | 107.6 | H93A—C93—H93B | 109.5 |
C51—C52—H52A | 109.5 | C9—C93—H93C | 109.5 |
C51—C52—H52B | 109.5 | H93A—C93—H93C | 109.5 |
H52A—C52—H52B | 109.5 | H93B—C93—H93C | 109.5 |
C1—O2—N3—C4 | −109.74 (12) | C4—C5—C51—C52 | −55.28 (13) |
C1—O2—N3—C31 | 93.12 (12) | C4—C5—N6—C7 | −75.00 (13) |
O2—N3—C4—O41 | −172.47 (10) | C51—C5—N6—C7 | 163.75 (10) |
C31—N3—C4—O41 | −17.60 (18) | C5—N6—C7—O71 | 4.23 (18) |
O2—N3—C4—C5 | 5.74 (15) | C5—N6—C7—O8 | −175.98 (10) |
C31—N3—C4—C5 | 160.61 (11) | O71—C7—O8—C9 | −13.45 (18) |
O41—C4—C5—N6 | −26.90 (16) | N6—C7—O8—C9 | 166.76 (10) |
N3—C4—C5—N6 | 154.95 (10) | C7—O8—C9—C92 | 70.40 (17) |
O41—C4—C5—C51 | 95.11 (13) | C7—O8—C9—C91 | −54.68 (15) |
N3—C4—C5—C51 | −83.05 (13) | C7—O8—C9—C93 | −170.33 (14) |
N6—C5—C51—C52 | 67.04 (13) |
D—H···A | D—H | H···A | D···A | D—H···A |
N6—H6···O41i | 0.85 (1) | 2.16 (1) | 3.0085 (13) | 176 (2) |
C52—H52C···O41i | 0.98 | 2.45 | 3.3376 (16) | 150 |
C31—H31B···O71ii | 0.98 | 2.36 | 3.3424 (16) | 177 |
C1—H1B···O71iii | 0.98 | 2.60 | 3.5589 (18) | 166 |
C93—H93C···O2iv | 0.98 | 2.56 | 3.5325 (18) | 172 |
Symmetry codes: (i) x−1/2, −y+1/2, −z+1; (ii) x+1/2, −y+3/2, −z+1; (iii) x−1/2, −y+3/2, −z+1; (iv) −x+1/2, −y+1, z−1/2. |
Experimental details
Crystal data | |
Chemical formula | C11H22N2O4 |
Mr | 246.31 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 123 |
a, b, c (Å) | 6.6315 (1), 9.8478 (2), 20.9769 (5) |
V (Å3) | 1369.91 (5) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.40 × 0.20 × 0.10 |
Data collection | |
Diffractometer | Nonius Kappa-CCD diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 19820, 3362, 3020 |
Rint | 0.032 |
(sin θ/λ)max (Å−1) | 0.667 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.034, 0.090, 1.07 |
No. of reflections | 3362 |
No. of parameters | 159 |
No. of restraints | 1 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.20, −0.29 |
Absolute structure | Flack H D (1983), Acta Cryst. A39, 876-881 |
Absolute structure parameter | 0.2 (8) |
Computer programs: COLLECT (Nonius, 1997–2000), HKL SCALEPACK (Otwinowski & Minor 1997), HKL DENZO (Otwinowski & Minor 1997) and SCALEPACK, SHELXS97 (Sheldrick, 1990), SHELXL97 (Sheldrick, 1997), SHELXTL-Plus (Sheldrick, 1991), SHELXL97.
C5—N6 | 1.4483 (14) | N6—H6 | 0.854 (13) |
C5—C51 | 1.5319 (17) | ||
C52—C51—C5 | 114.30 (10) | O71—C7—N6 | 124.15 (11) |
C5—N6—H6 | 122.2 (11) | ||
C1—O2—N3—C31 | 93.12 (12) | N6—C5—C51—C52 | 67.04 (13) |
N3—C4—C5—N6 | 154.95 (10) | C4—C5—N6—C7 | −75.00 (13) |
D—H···A | D—H | H···A | D···A | D—H···A |
N6—H6···O41i | 0.854 (13) | 2.156 (14) | 3.0085 (13) | 175.6 (15) |
C52—H52C···O41i | 0.98 | 2.45 | 3.3376 (16) | 149.7 |
C31—H31B···O71ii | 0.98 | 2.36 | 3.3424 (16) | 176.8 |
C1—H1B···O71iii | 0.98 | 2.60 | 3.5589 (18) | 165.5 |
C93—H93C···O2iv | 0.98 | 2.56 | 3.5325 (18) | 172.2 |
Symmetry codes: (i) x−1/2, −y+1/2, −z+1; (ii) x+1/2, −y+3/2, −z+1; (iii) x−1/2, −y+3/2, −z+1; (iv) −x+1/2, −y+1, z−1/2. |
N-methoxy-N-methyl-amides have been extensively used as carbonyl cation equivalents (Sibi, 1993). They are easy to prepare by several methods and show few side-reactions during nucleophilic addition or selective reduction to aldehydes. These advantages led us to the decision to use the title compound, (I), as an intermediate in alkylation reactions to prepare derivatives of a natural occurring lipid, sphingosine. Initially, compound (I) was prepared by Harbeson by a different route (Harbeson et al., 1994). The crystal structure of another N-methoxy-N-methyl-amide is reported by Zheng et al. (2000).
The underlying basis for the usefulness of N-methoxy-N-methyl-amides is the formation of a stable chelated tetrahedral intermediate after nucleophilic attack (Fig. 1), which prevents further additions to undesired side-products (Evans et al., 1991).
The structure of (I) with the atom numbering is shown in Fig. 2. Selected geometrical parameters are listed in Table 1. Within the crystal structure five intermolecular hydrogen bonds (Steiner, 2002) were found (Table 2). The four C—H···O hydrogen bonds are weak, whereas the N6—H6···O41 bond is a normal hydrogen bond. With the exception of the C52—H52C···O41 hydrogen bond in which the deviation from the ideal 180° torsion angle is 30.3°, all intermolecular hydrogen bonds are almost linear. Within the molecule, the torsion angle O2—N3—C4—O41 is −172.47 (10)° (nearly ideal antiperiplanar conformation). The conformation of (I), with a torsion angle of 60°, shows no similarity with the synclinal conformation assumed to occur in the chelated tetrahedral intermediate during nucleophilic attack.