Diastereomers (R_C,S_P)- and (R_C,R_P)-S-methyl P-(3-azido­prop­yl)-N-[(1R)-1-phenyl­ethyl]phospho­namido­thio­ate

Diastereoisomers of the title organophospho­rus compound, C₁₂H₁₉N₄OPS, denoted R_CS_P, (I), and R_CR_P, (II), were structurally characterized and compared. Asymmetric phosphorus compounds are of interest with regard to the use of these systems as possible protein probes via the stereoselective delivery of an azide group tethered to the P atom into key protein regions. The diastereomers were produced in a 1:1 mixture and isolated by chromatography. Although both isomers crystallize in the same space group with superficially similar cell constants, conformational and packing differences are pronounced. Despite the conformational differences, strong inter­molecular hydrogen bonding links both isomers into chains parallel to the a axis [N...O = 2.8609 (18) and 2.966 (3) Å in (I) and (II), respectively], with C—H...π inter­chain inter­actions of ca 3.5 Å.

S1. Comment

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 R_CS_P, (I), and R_CP_P, (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 R_CS_P 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 R_CS_P 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 R_CR_P 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 S_CS_P, namely S-(9-anthracenylmethyl) N-(1-phenylethyl)(ethoxyvinyl) thiophosphonamidate (Lee et al., 1992) and (S_P,S_C)-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).

Related literature

For related literature, see: Berkman et al. (1993); Bortoluzzi et al. (2004); Flack (1983); Lee et al. (1992); McQueney et al. (1991); Ordentlich et al. (1993); Rye & Baell (2005); Sussman et al. (1991); Thompson et al. (1992, 1993).

S2. Experimental

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): ν_max (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%.

S3. Refinement

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 U_iso constrained to be 1.2U_eq (for CH_arom and CH₂ H atoms; C—H = 0.95–1.00 Å) and 1.5U_eq (for CH₃; C—H = 0.98 Å) of the carrier atom.

Computing details

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).

Figures

	Fig. 1. The molecular structures of (a) (I) and (b) (II). Displacement ellipsoids are shown at the 30% probability level and H atoms are shown as spheres of arbitrary radii.
	Fig. 2. The packing of (a) (I) and (b) (II), viewed approximately parallel to the a axis. Cell axes are labelled and H atoms have been omitted for clarity. Hydrogen bonds are drawn with dashed lines.

(I) (R_C,S_P)-S-methyl P-(3-azidopropyl)-N-[(1R)-1-phenylethyl]phosphonamidothioate

Crystal data

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) Å^3	Needle, colourless
Z = 4	0.39 × 0.19 × 0.17 mm

Data collection

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

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.027	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.065	w = 1/[σ^2(Fo^2) + (0.0277P)^2 + 0.8071P] where P = (Fo^2 + 2Fc^2)/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)

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 (Ų)

	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)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
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)

Geometric parameters (Å, º)

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)

(II) (R_CR_P)-S-methyl P-(3-azidopropyl)-N-[(1R)-1-phenylethyl]phosphonamidothioate

Crystal data

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) Å^3	Needle, colourless
Z = 4	0.48 × 0.08 × 0.05 mm

Data collection

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

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.041	H-atom parameters constrained
wR(F^2) = 0.089	w = 1/[σ^2(Fo^2) + (0.039P)^2 + 0.3833P] where P = (Fo^2 + 2Fc^2)/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)

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 (Ų)

	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*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
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)

Geometric parameters (Å, º)

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)