Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270109009792/em3024sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270109009792/em3024Isup2.hkl | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270109009792/em3024IIsup3.hkl |
CCDC references: 730114; 730115
The title compounds were prepared by treating O-methyl (3-azopropyl) thiophosphonyl chloride (0.49 g, 2.3 mmol) with (R)-(+)-α-methylbenzylamine (1.2 ml, 9.2 mmol). Following chromatography (20% ether/hexane), methyl iodide (10 equivalents) was added and the solution was refluxed for 2 d. The solution was concentrated under reduced pressure to give a crude diastereomeric mixture of (I) and (II) (0.48 g, 1.6 mmol) in 70% yield and a diastereomeric ratio of 50:50. Silica gel chromatography (1–5% MeOH/CHCl3) separated pure fractions of the two diastereomers, which were subsequently recrystallized successively prior to diffraction analysis using diethyl ether and methanol/diethyl ether, respectively.
Isomer (I) was the faster eluting fraction and was recrystallized from diethyl ether: m.p. 368.7–369.0 K; [α]D20 = +23.6° (CHCl3); 1H NMR (400 MHz, CDCl3): δ 7.23–7.33 (5H, m), 4.46–4.56 (1H, m), 3.31 (2H, t, J = 6.5 Hz), 3.16 (1H, t, J = 10.2 Hz), 2.17 (3H, d, J = 12.6 Hz), 1.90–1.97 (2H, m), 1.81–1.87 (2H, m), 1.52 (3H, d, J = 6.7 Hz); 31P NMR (161.9 MHz, CDCl3): δ 49.5 (s).
Isomer (II) was collected as the slower eluting fraction and was dissolved in a minimal amount of methanol and crystallized by the slow addition of diethyl ether: m.p. 361.7–362.0 K; [α]D20 = +60.1° (CHCl3); 1H NMR (400 MHz, CDCl3): δ 7.22–7.33 (5H, m), 4.46–4.56 (1H, m), 3.31 (2H, t, J = 6.5 Hz), 3.23 (1H, t, J = 9.1 Hz), 2.16 (3H, d, J = 12.6 Hz), 1.81–1.87 (2H, m), 1.68–1.78 (2H, m), 1.52 (3H, d, J = 6.7 Hz); 31P NMR (161.9 MHz, CDCl3): δ 50.9 (s).
Composition analysis of the racemate (I/II): νmax (KBr, cm-1): 2099.25 (-N3); HRMS calculated m/z 299.1095, found m/z 299.1093 (M+H)+; analysis calculated for C12H19N4OPS: C 48.31, H 6.42, N 18.78%; found: C 48.30, H 6.44, N 18.68%.
Atom H8 was located via difference electron density maps in both (I) and (II), and the positional and thermal displacement parameters were refined freely in (I) but only the thermal displacement parameter was freely refined in (II) [this parameter does not have an s.u. value in CIF; please check; should H-atom treatment be `mixed'?]. All other H atoms were placed in idealized positions and refined using a riding model, with Uiso constrained to be 1.2Ueq (for CHarom and CH2 H atoms; C—H = 0.95–1.00 Å) and 1.5Ueq (for CH3; C—H = 0.98 Å) of the carrier atom.
For both compounds, data collection: SMART (Bruker, 2006); cell refinement: SAINT-Plus (Bruker, 2006); data reduction: SAINT-Plus (Bruker, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Version 6.14; Sheldrick, 2008); software used to prepare material for publication: publCIF (Westrip, 2009).
C12H19N4OPS | F(000) = 632 |
Mr = 298.34 | Dx = 1.326 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 9886 reflections |
a = 5.1896 (2) Å | θ = 2.4–30.0° |
b = 12.1755 (4) Å | µ = 0.32 mm−1 |
c = 23.6534 (8) Å | T = 90 K |
V = 1494.56 (9) Å3 | Needle, colourless |
Z = 4 | 0.39 × 0.19 × 0.17 mm |
Bruker SMART APEX diffractometer | 3437 independent reflections |
Radiation source: normal-focus sealed tube, Bruker SMART APEX | 3317 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.030 |
Detector resolution: 8.3 pixels mm-1 | θmax = 27.5°, θmin = 1.7° |
ω scans | h = −6→6 |
Absorption correction: multi-scan (SADABS; Bruker, 2007) | k = −15→15 |
Tmin = 0.885, Tmax = 0.947 | l = −30→30 |
22210 measured reflections |
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)] = 0.027 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.065 | w = 1/[σ2(Fo2) + (0.0277P)2 + 0.8071P] where P = (Fo2 + 2Fc2)/3 |
S = 0.99 | (Δ/σ)max = 0.001 |
3437 reflections | Δρmax = 0.39 e Å−3 |
178 parameters | Δρmin = −0.17 e Å−3 |
0 restraints | Absolute structure: Flack (1983), 1418 Friedel pairs |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: −0.01 (7) |
C12H19N4OPS | V = 1494.56 (9) Å3 |
Mr = 298.34 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 5.1896 (2) Å | µ = 0.32 mm−1 |
b = 12.1755 (4) Å | T = 90 K |
c = 23.6534 (8) Å | 0.39 × 0.19 × 0.17 mm |
Bruker SMART APEX diffractometer | 3437 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2007) | 3317 reflections with I > 2σ(I) |
Tmin = 0.885, Tmax = 0.947 | Rint = 0.030 |
22210 measured reflections |
R[F2 > 2σ(F2)] = 0.027 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.065 | Δρmax = 0.39 e Å−3 |
S = 0.99 | Δρmin = −0.17 e Å−3 |
3437 reflections | Absolute structure: Flack (1983), 1418 Friedel pairs |
178 parameters | Absolute structure parameter: −0.01 (7) |
0 restraints |
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 | ||
N1 | 1.1496 (5) | 0.18953 (16) | 1.04002 (7) | 0.0468 (5) | |
O1 | 1.2682 (2) | 0.21012 (9) | 0.74226 (5) | 0.0196 (2) | |
P1 | 1.02958 (7) | 0.26135 (3) | 0.765425 (16) | 0.01501 (9) | |
S1 | 1.14826 (8) | 0.41444 (3) | 0.794971 (17) | 0.01938 (9) | |
N2 | 1.1444 (3) | 0.13623 (13) | 1.00081 (6) | 0.0285 (3) | |
N3 | 1.1551 (3) | 0.07015 (13) | 0.96175 (6) | 0.0302 (3) | |
C4 | 0.9691 (3) | 0.08937 (14) | 0.91515 (7) | 0.0217 (3) | |
H4A | 0.8042 | 0.1161 | 0.9311 | 0.026* | |
H4B | 0.9350 | 0.0192 | 0.8954 | 0.026* | |
C5 | 1.0712 (3) | 0.17300 (14) | 0.87305 (6) | 0.0200 (3) | |
H5A | 1.2419 | 0.1490 | 0.8590 | 0.024* | |
H5B | 1.0933 | 0.2448 | 0.8921 | 0.024* | |
C6 | 0.8860 (3) | 0.18601 (13) | 0.82303 (6) | 0.0188 (3) | |
H6A | 0.7290 | 0.2249 | 0.8359 | 0.023* | |
H6B | 0.8338 | 0.1124 | 0.8095 | 0.023* | |
C7 | 0.8506 (4) | 0.46970 (14) | 0.82353 (7) | 0.0234 (3) | |
H7A | 0.7152 | 0.4658 | 0.7947 | 0.035* | |
H7B | 0.8772 | 0.5464 | 0.8346 | 0.035* | |
H7C | 0.7987 | 0.4267 | 0.8566 | 0.035* | |
N8 | 0.7897 (3) | 0.27537 (12) | 0.72194 (5) | 0.0177 (3) | |
C9 | 0.8178 (3) | 0.32483 (13) | 0.66563 (6) | 0.0164 (3) | |
H9 | 0.9823 | 0.3676 | 0.6651 | 0.020* | |
C10 | 0.5956 (3) | 0.40481 (14) | 0.65527 (7) | 0.0217 (3) | |
H10A | 0.4314 | 0.3656 | 0.6585 | 0.033* | |
H10B | 0.6113 | 0.4363 | 0.6173 | 0.033* | |
H10C | 0.6019 | 0.4638 | 0.6834 | 0.033* | |
C11 | 0.8330 (3) | 0.23789 (13) | 0.61960 (6) | 0.0173 (3) | |
C12 | 0.6552 (3) | 0.15203 (14) | 0.61826 (7) | 0.0219 (3) | |
H12 | 0.5249 | 0.1478 | 0.6464 | 0.026* | |
C13 | 0.6668 (4) | 0.07305 (15) | 0.57639 (7) | 0.0259 (4) | |
H13 | 0.5443 | 0.0151 | 0.5758 | 0.031* | |
C14 | 0.8569 (4) | 0.07808 (16) | 0.53508 (7) | 0.0256 (4) | |
H14 | 0.8653 | 0.0232 | 0.5066 | 0.031* | |
C15 | 1.0339 (4) | 0.16303 (15) | 0.53550 (7) | 0.0257 (4) | |
H15 | 1.1633 | 0.1670 | 0.5072 | 0.031* | |
C16 | 1.0214 (3) | 0.24269 (14) | 0.57773 (6) | 0.0213 (3) | |
H16 | 1.1429 | 0.3010 | 0.5780 | 0.026* | |
H8 | 0.648 (4) | 0.2545 (15) | 0.7308 (8) | 0.019 (5)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0717 (14) | 0.0388 (10) | 0.0299 (9) | −0.0150 (11) | −0.0117 (10) | −0.0019 (8) |
O1 | 0.0149 (5) | 0.0225 (5) | 0.0214 (6) | −0.0001 (4) | 0.0022 (5) | −0.0010 (5) |
P1 | 0.01263 (17) | 0.01786 (19) | 0.01453 (17) | −0.00096 (14) | 0.00026 (14) | 0.00017 (15) |
S1 | 0.01482 (17) | 0.01911 (18) | 0.02421 (19) | −0.00254 (16) | 0.00027 (16) | −0.00242 (16) |
N2 | 0.0365 (8) | 0.0282 (8) | 0.0209 (7) | −0.0073 (7) | −0.0064 (7) | 0.0088 (6) |
N3 | 0.0379 (9) | 0.0324 (8) | 0.0205 (7) | 0.0070 (8) | −0.0041 (7) | 0.0051 (6) |
C4 | 0.0251 (8) | 0.0223 (7) | 0.0179 (7) | 0.0023 (8) | −0.0007 (7) | 0.0010 (6) |
C5 | 0.0197 (8) | 0.0222 (8) | 0.0182 (7) | −0.0003 (7) | −0.0008 (6) | 0.0013 (6) |
C6 | 0.0184 (8) | 0.0207 (7) | 0.0172 (7) | −0.0018 (6) | 0.0014 (6) | 0.0022 (6) |
C7 | 0.0194 (8) | 0.0221 (8) | 0.0286 (9) | 0.0021 (7) | 0.0030 (8) | −0.0044 (7) |
N8 | 0.0116 (6) | 0.0255 (7) | 0.0158 (6) | −0.0031 (5) | 0.0002 (5) | 0.0026 (5) |
C9 | 0.0129 (7) | 0.0204 (7) | 0.0161 (7) | −0.0031 (6) | 0.0000 (6) | 0.0038 (6) |
C10 | 0.0197 (8) | 0.0223 (8) | 0.0231 (8) | 0.0014 (7) | 0.0009 (6) | 0.0027 (6) |
C11 | 0.0148 (7) | 0.0222 (8) | 0.0150 (7) | 0.0021 (7) | −0.0023 (6) | 0.0038 (6) |
C12 | 0.0201 (8) | 0.0264 (8) | 0.0193 (8) | −0.0023 (7) | 0.0028 (6) | 0.0007 (6) |
C13 | 0.0237 (8) | 0.0280 (9) | 0.0259 (8) | −0.0062 (8) | 0.0001 (7) | −0.0023 (7) |
C14 | 0.0247 (8) | 0.0306 (9) | 0.0214 (8) | 0.0022 (8) | −0.0024 (7) | −0.0056 (7) |
C15 | 0.0194 (8) | 0.0382 (10) | 0.0195 (8) | 0.0011 (8) | 0.0023 (7) | −0.0009 (7) |
C16 | 0.0168 (7) | 0.0273 (8) | 0.0197 (7) | −0.0025 (7) | 0.0004 (6) | 0.0023 (6) |
N1—N2 | 1.132 (2) | N8—C9 | 1.4691 (19) |
O1—P1 | 1.4911 (12) | N8—H8 | 0.81 (2) |
P1—N8 | 1.6239 (14) | C9—C11 | 1.520 (2) |
P1—C6 | 1.8037 (16) | C9—C10 | 1.529 (2) |
P1—S1 | 2.0838 (6) | C9—H9 | 1.0000 |
S1—C7 | 1.8152 (18) | C10—H10A | 0.9800 |
N2—N3 | 1.226 (2) | C10—H10B | 0.9800 |
N3—C4 | 1.484 (2) | C10—H10C | 0.9800 |
C4—C5 | 1.520 (2) | C11—C16 | 1.393 (2) |
C4—H4A | 0.9900 | C11—C12 | 1.395 (2) |
C4—H4B | 0.9900 | C12—C13 | 1.382 (2) |
C5—C6 | 1.533 (2) | C12—H12 | 0.9500 |
C5—H5A | 0.9900 | C13—C14 | 1.390 (2) |
C5—H5B | 0.9900 | C13—H13 | 0.9500 |
C6—H6A | 0.9900 | C14—C15 | 1.383 (3) |
C6—H6B | 0.9900 | C14—H14 | 0.9500 |
C7—H7A | 0.9800 | C15—C16 | 1.394 (2) |
C7—H7B | 0.9800 | C15—H15 | 0.9500 |
C7—H7C | 0.9800 | C16—H16 | 0.9500 |
O1—P1—N8 | 116.63 (7) | C9—N8—P1 | 122.76 (11) |
O1—P1—C6 | 114.08 (7) | C9—N8—H8 | 117.1 (13) |
N8—P1—C6 | 102.43 (7) | P1—N8—H8 | 120.1 (13) |
O1—P1—S1 | 104.59 (5) | N8—C9—C11 | 111.66 (13) |
N8—P1—S1 | 110.18 (5) | N8—C9—C10 | 109.35 (13) |
C6—P1—S1 | 108.88 (6) | C11—C9—C10 | 111.58 (13) |
C7—S1—P1 | 101.82 (6) | N8—C9—H9 | 108.0 |
N1—N2—N3 | 172.7 (2) | C11—C9—H9 | 108.0 |
N2—N3—C4 | 115.25 (16) | C10—C9—H9 | 108.0 |
N3—C4—C5 | 111.44 (14) | C9—C10—H10A | 109.5 |
N3—C4—H4A | 109.3 | C9—C10—H10B | 109.5 |
C5—C4—H4A | 109.3 | H10A—C10—H10B | 109.5 |
N3—C4—H4B | 109.3 | C9—C10—H10C | 109.5 |
C5—C4—H4B | 109.3 | H10A—C10—H10C | 109.5 |
H4A—C4—H4B | 108.0 | H10B—C10—H10C | 109.5 |
C4—C5—C6 | 110.88 (13) | C16—C11—C12 | 118.67 (15) |
C4—C5—H5A | 109.5 | C16—C11—C9 | 121.09 (14) |
C6—C5—H5A | 109.5 | C12—C11—C9 | 120.24 (14) |
C4—C5—H5B | 109.5 | C13—C12—C11 | 120.60 (16) |
C6—C5—H5B | 109.5 | C13—C12—H12 | 119.7 |
H5A—C5—H5B | 108.1 | C11—C12—H12 | 119.7 |
C5—C6—P1 | 112.13 (11) | C12—C13—C14 | 120.27 (17) |
C5—C6—H6A | 109.2 | C12—C13—H13 | 119.9 |
P1—C6—H6A | 109.2 | C14—C13—H13 | 119.9 |
C5—C6—H6B | 109.2 | C15—C14—C13 | 119.95 (16) |
P1—C6—H6B | 109.2 | C15—C14—H14 | 120.0 |
H6A—C6—H6B | 107.9 | C13—C14—H14 | 120.0 |
S1—C7—H7A | 109.5 | C14—C15—C16 | 119.63 (16) |
S1—C7—H7B | 109.5 | C14—C15—H15 | 120.2 |
H7A—C7—H7B | 109.5 | C16—C15—H15 | 120.2 |
S1—C7—H7C | 109.5 | C11—C16—C15 | 120.88 (16) |
H7A—C7—H7C | 109.5 | C11—C16—H16 | 119.6 |
H7B—C7—H7C | 109.5 | C15—C16—H16 | 119.6 |
O1—P1—S1—C7 | −178.87 (8) | P1—N8—C9—C10 | −135.65 (12) |
N8—P1—S1—C7 | 55.04 (8) | N8—C9—C11—C16 | −132.84 (15) |
C6—P1—S1—C7 | −56.55 (9) | C10—C9—C11—C16 | 104.45 (16) |
N2—N3—C4—C5 | 84.1 (2) | N8—C9—C11—C12 | 47.90 (19) |
N3—C4—C5—C6 | 175.98 (14) | C10—C9—C11—C12 | −74.81 (18) |
C4—C5—C6—P1 | −167.69 (11) | C16—C11—C12—C13 | 0.4 (2) |
O1—P1—C6—C5 | 59.11 (13) | C9—C11—C12—C13 | 179.63 (15) |
N8—P1—C6—C5 | −173.94 (11) | C11—C12—C13—C14 | 0.2 (3) |
S1—P1—C6—C5 | −57.28 (12) | C12—C13—C14—C15 | −0.6 (3) |
O1—P1—N8—C9 | −49.64 (15) | C13—C14—C15—C16 | 0.5 (3) |
C6—P1—N8—C9 | −174.94 (13) | C12—C11—C16—C15 | −0.5 (2) |
S1—P1—N8—C9 | 69.34 (13) | C9—C11—C16—C15 | −179.76 (15) |
P1—N8—C9—C11 | 100.38 (14) | C14—C15—C16—C11 | 0.1 (3) |
C12H19N4OPS | F(000) = 632 |
Mr = 298.34 | Dx = 1.348 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 5278 reflections |
a = 5.4509 (3) Å | θ = 2.5–29.4° |
b = 12.0987 (6) Å | µ = 0.33 mm−1 |
c = 22.2882 (11) Å | T = 90 K |
V = 1469.88 (13) Å3 | Needle, colourless |
Z = 4 | 0.48 × 0.08 × 0.05 mm |
Bruker SMART APEX diffractometer | 3372 independent reflections |
Radiation source: normal-focus sealed tube, Bruker SMART APEX | 2858 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.074 |
Detector resolution: 8.3 pixels mm-1 | θmax = 27.5°, θmin = 1.8° |
ω scans | h = −7→7 |
Absorption correction: multi-scan (SADABS; Bruker, 2007) | k = −15→15 |
Tmin = 0.859, Tmax = 0.984 | l = −28→28 |
21644 measured reflections |
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)] = 0.041 | H-atom parameters constrained |
wR(F2) = 0.089 | w = 1/[σ2(Fo2) + (0.039P)2 + 0.3833P] where P = (Fo2 + 2Fc2)/3 |
S = 1.02 | (Δ/σ)max < 0.001 |
3372 reflections | Δρmax = 0.50 e Å−3 |
174 parameters | Δρmin = −0.24 e Å−3 |
0 restraints | Absolute structure: Flack (1983), 1397 Friedel pairs |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0.05 (10) |
C12H19N4OPS | V = 1469.88 (13) Å3 |
Mr = 298.34 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 5.4509 (3) Å | µ = 0.33 mm−1 |
b = 12.0987 (6) Å | T = 90 K |
c = 22.2882 (11) Å | 0.48 × 0.08 × 0.05 mm |
Bruker SMART APEX diffractometer | 3372 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2007) | 2858 reflections with I > 2σ(I) |
Tmin = 0.859, Tmax = 0.984 | Rint = 0.074 |
21644 measured reflections |
R[F2 > 2σ(F2)] = 0.041 | H-atom parameters constrained |
wR(F2) = 0.089 | Δρmax = 0.50 e Å−3 |
S = 1.02 | Δρmin = −0.24 e Å−3 |
3372 reflections | Absolute structure: Flack (1983), 1397 Friedel pairs |
174 parameters | Absolute structure parameter: 0.05 (10) |
0 restraints |
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 | ||
N1 | 0.0783 (5) | 1.2356 (2) | 0.03721 (12) | 0.0307 (6) | |
P1 | 0.66219 (12) | 0.80546 (5) | 0.10130 (3) | 0.01266 (14) | |
O1 | 0.9090 (3) | 0.75404 (14) | 0.09660 (8) | 0.0160 (4) | |
S1 | 0.64234 (12) | 0.91951 (5) | 0.17155 (3) | 0.01595 (15) | |
N2 | 0.0831 (4) | 1.1555 (2) | 0.01101 (10) | 0.0203 (5) | |
N3 | 0.0614 (4) | 1.0707 (2) | −0.01905 (10) | 0.0221 (5) | |
C4 | 0.2864 (5) | 1.0014 (2) | −0.02288 (12) | 0.0182 (6) | |
H4A | 0.4268 | 1.0481 | −0.0351 | 0.022* | |
H4B | 0.2630 | 0.9438 | −0.0539 | 0.022* | |
C5 | 0.3441 (5) | 0.9465 (2) | 0.03690 (11) | 0.0168 (5) | |
H5A | 0.2044 | 0.8992 | 0.0489 | 0.020* | |
H5B | 0.3656 | 1.0041 | 0.0680 | 0.020* | |
C6 | 0.5776 (5) | 0.8759 (2) | 0.03332 (11) | 0.0152 (5) | |
H6A | 0.7155 | 0.9242 | 0.0212 | 0.018* | |
H6B | 0.5552 | 0.8200 | 0.0013 | 0.018* | |
C7 | 0.8945 (5) | 1.0105 (2) | 0.15251 (12) | 0.0213 (6) | |
H7A | 1.0496 | 0.9700 | 0.1559 | 0.032* | |
H7B | 0.8961 | 1.0736 | 0.1801 | 0.032* | |
H7C | 0.8741 | 1.0370 | 0.1113 | 0.032* | |
N8 | 0.4418 (4) | 0.71603 (17) | 0.11381 (9) | 0.0137 (5) | |
H8 | 0.2923 | 0.7351 | 0.1058 | 0.012* | |
C9 | 0.4559 (5) | 0.6356 (2) | 0.16397 (11) | 0.0152 (5) | |
H9 | 0.6245 | 0.6030 | 0.1639 | 0.018* | |
C10 | 0.2749 (5) | 0.5425 (2) | 0.15310 (12) | 0.0196 (6) | |
H10A | 0.2895 | 0.4876 | 0.1853 | 0.029* | |
H10B | 0.3105 | 0.5074 | 0.1144 | 0.029* | |
H10C | 0.1077 | 0.5723 | 0.1526 | 0.029* | |
C11 | 0.4151 (4) | 0.6892 (2) | 0.22498 (11) | 0.0140 (5) | |
C12 | 0.5839 (5) | 0.6744 (2) | 0.27098 (12) | 0.0209 (6) | |
H12 | 0.7234 | 0.6288 | 0.2645 | 0.025* | |
C13 | 0.5517 (5) | 0.7252 (2) | 0.32603 (13) | 0.0274 (7) | |
H13 | 0.6682 | 0.7142 | 0.3572 | 0.033* | |
C14 | 0.3500 (6) | 0.7918 (2) | 0.33561 (12) | 0.0286 (7) | |
H14 | 0.3293 | 0.8278 | 0.3731 | 0.034* | |
C15 | 0.1767 (5) | 0.8063 (2) | 0.29041 (12) | 0.0241 (6) | |
H15 | 0.0367 | 0.8513 | 0.2973 | 0.029* | |
C16 | 0.2089 (5) | 0.7550 (2) | 0.23542 (12) | 0.0188 (6) | |
H16 | 0.0901 | 0.7645 | 0.2047 | 0.023* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0250 (14) | 0.0285 (14) | 0.0386 (15) | 0.0056 (11) | −0.0026 (12) | −0.0061 (12) |
P1 | 0.0106 (3) | 0.0145 (3) | 0.0129 (3) | 0.0007 (3) | 0.0000 (3) | −0.0009 (3) |
O1 | 0.0096 (8) | 0.0183 (9) | 0.0201 (9) | 0.0020 (7) | 0.0001 (7) | −0.0017 (8) |
S1 | 0.0143 (3) | 0.0184 (3) | 0.0151 (3) | −0.0012 (3) | 0.0012 (3) | −0.0026 (3) |
N2 | 0.0143 (12) | 0.0229 (13) | 0.0237 (12) | 0.0023 (10) | −0.0020 (10) | 0.0049 (11) |
N3 | 0.0218 (12) | 0.0199 (12) | 0.0246 (13) | 0.0038 (10) | −0.0054 (10) | 0.0001 (10) |
C4 | 0.0186 (15) | 0.0179 (14) | 0.0183 (14) | 0.0015 (11) | −0.0011 (10) | 0.0015 (11) |
C5 | 0.0134 (12) | 0.0208 (13) | 0.0162 (12) | 0.0009 (12) | 0.0018 (11) | 0.0037 (10) |
C6 | 0.0161 (13) | 0.0175 (13) | 0.0121 (12) | 0.0001 (10) | 0.0001 (10) | 0.0026 (10) |
C7 | 0.0170 (15) | 0.0212 (14) | 0.0256 (15) | −0.0049 (11) | 0.0051 (11) | −0.0060 (11) |
N8 | 0.0078 (9) | 0.0187 (12) | 0.0147 (11) | −0.0003 (9) | −0.0017 (8) | 0.0015 (9) |
C9 | 0.0124 (12) | 0.0156 (13) | 0.0178 (14) | 0.0028 (10) | 0.0008 (11) | 0.0018 (11) |
C10 | 0.0212 (15) | 0.0179 (14) | 0.0198 (14) | −0.0003 (11) | 0.0019 (11) | 0.0009 (11) |
C11 | 0.0129 (12) | 0.0150 (12) | 0.0140 (12) | −0.0050 (10) | 0.0005 (9) | 0.0031 (10) |
C12 | 0.0166 (13) | 0.0252 (16) | 0.0210 (14) | −0.0050 (11) | −0.0010 (11) | 0.0057 (11) |
C13 | 0.0269 (14) | 0.0375 (18) | 0.0179 (14) | −0.0116 (13) | −0.0060 (13) | 0.0064 (13) |
C14 | 0.0383 (16) | 0.0322 (16) | 0.0154 (13) | −0.0157 (16) | 0.0066 (14) | −0.0043 (12) |
C15 | 0.0246 (15) | 0.0219 (14) | 0.0258 (14) | −0.0052 (14) | 0.0090 (12) | −0.0020 (12) |
C16 | 0.0161 (14) | 0.0196 (14) | 0.0207 (14) | −0.0026 (11) | 0.0008 (10) | 0.0035 (12) |
N1—N2 | 1.131 (3) | N8—C9 | 1.484 (3) |
P1—O1 | 1.4858 (17) | N8—H8 | 0.8654 |
P1—N8 | 1.641 (2) | C9—C10 | 1.517 (4) |
P1—C6 | 1.798 (3) | C9—C11 | 1.523 (3) |
P1—S1 | 2.0898 (9) | C9—H9 | 1.0000 |
S1—C7 | 1.811 (3) | C10—H10A | 0.9800 |
N2—N3 | 1.231 (3) | C10—H10B | 0.9800 |
N3—C4 | 1.488 (3) | C10—H10C | 0.9800 |
C4—C5 | 1.522 (3) | C11—C12 | 1.390 (3) |
C4—H4A | 0.9900 | C11—C16 | 1.396 (4) |
C4—H4B | 0.9900 | C12—C13 | 1.383 (4) |
C5—C6 | 1.535 (4) | C12—H12 | 0.9500 |
C5—H5A | 0.9900 | C13—C14 | 1.379 (4) |
C5—H5B | 0.9900 | C13—H13 | 0.9500 |
C6—H6A | 0.9900 | C14—C15 | 1.392 (4) |
C6—H6B | 0.9900 | C14—H14 | 0.9500 |
C7—H7A | 0.9800 | C15—C16 | 1.385 (4) |
C7—H7B | 0.9800 | C15—H15 | 0.9500 |
C7—H7C | 0.9800 | C16—H16 | 0.9500 |
O1—P1—N8 | 113.50 (11) | C9—N8—P1 | 121.50 (16) |
O1—P1—C6 | 111.79 (11) | C9—N8—H8 | 112.2 |
N8—P1—C6 | 105.54 (11) | P1—N8—H8 | 118.6 |
O1—P1—S1 | 112.10 (8) | N8—C9—C10 | 109.4 (2) |
N8—P1—S1 | 105.68 (8) | N8—C9—C11 | 112.7 (2) |
C6—P1—S1 | 107.77 (9) | C10—C9—C11 | 111.3 (2) |
C7—S1—P1 | 100.74 (9) | N8—C9—H9 | 107.7 |
N1—N2—N3 | 172.9 (3) | C10—C9—H9 | 107.7 |
N2—N3—C4 | 115.0 (2) | C11—C9—H9 | 107.7 |
N3—C4—C5 | 111.5 (2) | C9—C10—H10A | 109.5 |
N3—C4—H4A | 109.3 | C9—C10—H10B | 109.5 |
C5—C4—H4A | 109.3 | H10A—C10—H10B | 109.5 |
N3—C4—H4B | 109.3 | C9—C10—H10C | 109.5 |
C5—C4—H4B | 109.3 | H10A—C10—H10C | 109.5 |
H4A—C4—H4B | 108.0 | H10B—C10—H10C | 109.5 |
C4—C5—C6 | 111.7 (2) | C12—C11—C16 | 118.9 (2) |
C4—C5—H5A | 109.3 | C12—C11—C9 | 120.5 (2) |
C6—C5—H5A | 109.3 | C16—C11—C9 | 120.6 (2) |
C4—C5—H5B | 109.3 | C13—C12—C11 | 120.9 (3) |
C6—C5—H5B | 109.3 | C13—C12—H12 | 119.6 |
H5A—C5—H5B | 108.0 | C11—C12—H12 | 119.6 |
C5—C6—P1 | 115.63 (17) | C14—C13—C12 | 119.9 (3) |
C5—C6—H6A | 108.4 | C14—C13—H13 | 120.1 |
P1—C6—H6A | 108.4 | C12—C13—H13 | 120.1 |
C5—C6—H6B | 108.4 | C13—C14—C15 | 120.2 (3) |
P1—C6—H6B | 108.4 | C13—C14—H14 | 119.9 |
H6A—C6—H6B | 107.4 | C15—C14—H14 | 119.9 |
S1—C7—H7A | 109.5 | C16—C15—C14 | 119.8 (3) |
S1—C7—H7B | 109.5 | C16—C15—H15 | 120.1 |
H7A—C7—H7B | 109.5 | C14—C15—H15 | 120.1 |
S1—C7—H7C | 109.5 | C15—C16—C11 | 120.3 (3) |
H7A—C7—H7C | 109.5 | C15—C16—H16 | 119.8 |
H7B—C7—H7C | 109.5 | C11—C16—H16 | 119.8 |
O1—P1—S1—C7 | 55.22 (12) | P1—N8—C9—C11 | 73.5 (2) |
N8—P1—S1—C7 | 179.34 (13) | N8—C9—C11—C12 | −127.0 (2) |
C6—P1—S1—C7 | −68.20 (13) | C10—C9—C11—C12 | 109.6 (3) |
N2—N3—C4—C5 | 70.1 (3) | N8—C9—C11—C16 | 52.3 (3) |
N3—C4—C5—C6 | −179.4 (2) | C10—C9—C11—C16 | −71.1 (3) |
C4—C5—C6—P1 | −179.29 (18) | C16—C11—C12—C13 | −1.1 (4) |
O1—P1—C6—C5 | −170.99 (17) | C9—C11—C12—C13 | 178.3 (2) |
N8—P1—C6—C5 | 65.2 (2) | C11—C12—C13—C14 | −0.2 (4) |
S1—P1—C6—C5 | −47.4 (2) | C12—C13—C14—C15 | 1.2 (4) |
O1—P1—N8—C9 | 52.4 (2) | C13—C14—C15—C16 | −0.9 (4) |
C6—P1—N8—C9 | 175.19 (19) | C14—C15—C16—C11 | −0.4 (4) |
S1—P1—N8—C9 | −70.80 (19) | C12—C11—C16—C15 | 1.4 (4) |
P1—N8—C9—C10 | −162.08 (17) | C9—C11—C16—C15 | −178.0 (2) |
Experimental details
(I) | (II) | |
Crystal data | ||
Chemical formula | C12H19N4OPS | C12H19N4OPS |
Mr | 298.34 | 298.34 |
Crystal system, space group | Orthorhombic, P212121 | Orthorhombic, P212121 |
Temperature (K) | 90 | 90 |
a, b, c (Å) | 5.1896 (2), 12.1755 (4), 23.6534 (8) | 5.4509 (3), 12.0987 (6), 22.2882 (11) |
V (Å3) | 1494.56 (9) | 1469.88 (13) |
Z | 4 | 4 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.32 | 0.33 |
Crystal size (mm) | 0.39 × 0.19 × 0.17 | 0.48 × 0.08 × 0.05 |
Data collection | ||
Diffractometer | Bruker SMART APEX diffractometer | Bruker SMART APEX diffractometer |
Absorption correction | Multi-scan (SADABS; Bruker, 2007) | Multi-scan (SADABS; Bruker, 2007) |
Tmin, Tmax | 0.885, 0.947 | 0.859, 0.984 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 22210, 3437, 3317 | 21644, 3372, 2858 |
Rint | 0.030 | 0.074 |
(sin θ/λ)max (Å−1) | 0.650 | 0.650 |
Refinement | ||
R[F2 > 2σ(F2)], wR(F2), S | 0.027, 0.065, 0.99 | 0.041, 0.089, 1.02 |
No. of reflections | 3437 | 3372 |
No. of parameters | 178 | 174 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.39, −0.17 | 0.50, −0.24 |
Absolute structure | Flack (1983), 1418 Friedel pairs | Flack (1983), 1397 Friedel pairs |
Absolute structure parameter | −0.01 (7) | 0.05 (10) |
Computer programs: SMART (Bruker, 2006), SAINT-Plus (Bruker, 2006), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), XP in SHELXTL (Version 6.14; Sheldrick, 2008), publCIF (Westrip, 2009).
(I) | (II) | |
O1—P1 | 1.4911 (12) | 1.4858 (17) |
P1—N8 | 1.6239 (14) | 1.641 (2) |
P1—C6 | 1.8037 (16) | 1.798 (3) |
P1—S1 | 2.0838 (6) | 2.0898 (9) |
N8—C9 | 1.4691 (19) | 1.484 (3) |
C9—C10 | 1.529 (2) | 1.517 (4) |
C9—C11 | 1.520 (2) | 1.523 (3) |
O1—P1—N8—C9 | -49.64 (15) | 52.4 (2) |
C6—P1—N8—C9 | -174.94 (13) | 175.19 (19) |
S1—P1—N8—C9 | 69.34 (13) | -70.80 (19) |
P1—N8—C9—C11 | 100.38 (14) | 73.5 (2) |
P1—N8—C9—C10 | -135.65 (12) | -162.08 (17) |
D—H···A | D—H | H···A | D···A | D—H···A | |
(I) | N8—H8···O1i | 0.81 (2) | 2.06 (2) | 2.8609 (18) | 171.6 (18) |
(II) | N8—H8···O1i | 0.87 | 2.11 | 2.966 (3) | 169 |
Symmetry code: (i) x-1, y, z. |
Organophosphates (OPs) are a well known class of structures with particular utility as insecticides and increasing involvement in protein mechanisms as inhibitors, substrates, transition state analogs and isosteres (Rye & Baell, 2005). One of the key structural features of OPs is the potential to bear a center of asymmetry at phosphorus. This important variable allows researchers to investigate the role of stereoisomerism in studies with biological targets. For example, asymmetric phosphorus esters interact stereospecifically with enzymes, receptors and transporters (Thompson et al., 1992, 1993; Berkman et al., 1993). Numerous routes to asymmetric OP compounds are known but few have been structurally assigned. Our current interest in asymmetric phosphorus compounds resides in their possible application as probes of proteins in which an azide group tethered to the P atom can be stereoselectively delivered into key protein regions, e.g. the `gorge' in acetylcholinesterases (Sussman et al., 1991; Ordentlich et al., 1993).
Our goal was to prepare the stereoisomeric forms of azide-tethered OPs [structures RCSP, (I), and RCPP, (II)] for use as photoaffinity probes. Pure phosphonamide diastereomers were produced by the reaction of (R)-(+)-α-methylbenzylamine with a racemic mixture of O-methyl 3-azidopropyl thiophosphonyl chloride followed by S-to-O isomerization to afford the corresponding diastereomers in a 1:1 ratio. Attempts at isolation by crystallization result in small quantities of noncrystalline precipitate in a diethyl ether/minimal methanol mix. This material was difficult to isolate and clean well enough to identify whether it was a single diastereomer or a mixture. Separation by chromatography was clean and more predictable than direct separation by crystallization/co-crystallization and was used to isolate each isomer. This method, used previously to isolate stereoisomers (Bortoluzzi et al., 2004), provided good yields of both (I) and (II), which readily crystallized from diethyl ether and methanol/diethyl ether solutions.
Both compounds crystallize in the same space group, P212121, and the chirality was determined by refinement of the Flack (1983) parameter in conjunction with the known chiral carbon center. The cell parameters are similar for each compound, but with significant differences evident in the a and c axial lengths (differences of ca 0.26 and 1.37 Å, respectively), with compound (I), the RCSP isomer, having the larger cell.
The molecular species are shown in Fig. 1 and selected geometric parameters are given in Table 1. The bonding patterns within the two systems are very similar around each stereocenter, the largest difference of ca 0.02 Å being in the P1—N8 and N8—C9 bonds. Conformational differences are much more pronounced and are reflected in the differences in the torsion angles between the two compounds. Compound (I), the RCSP isomer, shown in Fig. 1(a), is in a more `relaxed' conformation, with the aliphatic chain forming a straight backbone with respect to the N8—C9 vector. The azide, SMe and C10 groups are on the same side of this chain, and the phenyl group and the oxide occupy the other side. Compound (II), the RCRP isomer, shown in Fig. 1(b), is twisted, with the azide curling back towards the phenyl group. The phenyl, SMe and azide groups are on the same side of the chain, with the sulfur in the SMe group ca 3.2 Å from the phenyl ring plane. The conformational differences – relaxed and twisted forms – have also been seen previously in other stereoisomers (Bortoluzzi et al., 2004).
Changes in conformation are reflected in the packing of each system. Each phosphine oxide acts as a hydrogen-bond acceptor for the amino group (N8, see below) which generates a strong intermolecular hydrogen bond linking the molecules into chains parallel to the a axis. The twofold axis in both (I) and (II) dictates the placement of the azide group; however, the conformational differences between the structures result in the azide moieties wrapping around each other in (I) and facing each other in (II), both in alternating patterns (see Fig. 2). Intermolecular distances between the terminal azide N atoms in (I) and (II) are ca 3.5 and 3.2 Å, respectively. In both (I) and (II) there is also a close intermolecular contact between C7 (thiomethyl) and an adjacent phenyl group with a C—H···π plane distance of ca 3.5 Å.
Two closely related phosphonamidothioates, both SCSP, namely S-(9-anthracenylmethyl) N-(1-phenylethyl)(ethoxyvinyl) thiophosphonamidate (Lee et al., 1992) and (SP,SC)-S-[2-(4-nitrophenyl)]-2-oxoethyl N,P-dimethyl-N-(1-phenylethyl)phosphonamidothioate (McQueney et al., 1991) have been reported. These molecules have similar bonding patterns to (I) and (II) but have very different intermolecular interactions. The former compound displays a similar hydrogen-bonding synthon (e.g. N···O = ca 2.96 Å) and the S atom is ca. 3.5 Å from the phenyl ring substituent, as seen in (I) and (II). The latter compound is much more complex with many hydrogen-bonding interactions, unlike (I) or (II).