supplementary materials


bt2512 scheme

Acta Cryst. (2007). E63, o4148    [ doi:10.1107/S1600536807045576 ]

rac-Diethyl [(1S,2R)-1-(4-bromophenyl)-6-hydroxy-3-oxo-2,3-dihydro-1H-benzo[f]chromen-2-yl]phosphonate

H. Krawczyk, L. Albrecht, J. Wojciechowski and W. M. Wolf

Abstract top

In the title compound, C23H22BrO6P, the [delta]-valerolactone ring adopts a distorted screw-boat conformation, with the diethoxyphosphoryl substituent occupying an axial position. An unusual eclipsed conformation is found for the P-C bond. The molecules form centrosymmetric dimers connected by O-H...O hydrogen bonds. One of the methyl groups is disordered, with site occupancies of ca 0.8:0.2.

Comment top

Neoflavonoids show a wide range of biological activities (Bailly et al., 2003; Zhang et al., 2006; Roelens et al., 2005). The title compound is a key product in the novel synthesis of 4-aryl-3,4-dihydrocoumarins based on CF3SO3H promoted Friedel Crafts reaction of electron-rich hydroxyarenes with the acids bearing electron-withdrawing substituents on the aromatic ring (Krawczyk et al., 2007). A view of (I), with atom numbering scheme is shown in Fig. 1. The δ-valerolactone and naphthalene moieties are almost coplanar with one another. The former ring adopts conformation close to a 4S3 screw-boat (Boeyens, 1978), with O1, C1, C3, C4 and C9 almost coplanar (the average r.m.s. deviation from the mean plane is 0.05 Å) and C2 situated at the flap. The Cremer & Pople (1975) puckering parameters for the ring atom sequence O1/C1/C2/C3/C4/C9 are: Q = 0.48 (2) Å, θ = 116.6 (2) and φ = 315.84 (2)°. Both exocyclic substituents, namely the diethoxyphosphoryl and phenyl groups occupy axial positions in respect to the δ-valerolactone ring. The former adopts unusual eclipsed conformation when looking along the C2—P bond (Fig. 2). This particular arrangement is locked by either Coulombic attraction between phosphoryl O4 and carbonyl C1 or the C—H···π(naphthalene) interactions [H223···C5 2.89 (2) Å]. In the crystal molecules form centrosymmetric dimers connected by strong hydrogen bonds linking phosphoryl and hydroxyl groups of both monomers. In terms of Etter's graph-set terminology (Etter, 1990; Bernstein et al., 1995) this system can be described as R22(20). The Br atom is involved in a short contact [3.183 (1) Å] with the endocyclic O1 atom of the neighbouring [0.5 − x, y − 1/2, 0.5 − z] molecule.

Related literature top

For related literature, see: Bernstein et al. (1995); Boeyens (1978); Cremer & Pople (1975); Etter (1990); Krawczyk et al. (2007). For biologically active 4-aryl-3,4-dihydrocoumarins, see: Bailly et al. (2003; Zhang et al. (2006); Roelens et al. (2005).

Experimental top

The CF3SO3H promoted Friedel Crafts reaction of electron-rich hydroxyarenes with the acids bearing electron-withdrawing substituents on the aromatic ring. Details of the synthesis are published elsewhere (Krawczyk et al., 2007). Good quality single crystals were obtained from the ethyl ether solution.

Refinement top

The C23 atom of the diethoxyphosphoryl group displayed conformational disorder and was refined in a two-site disorder model. The occupancy of the major component refined to a value of 0.825 (5). H atoms were located on a difference Fourier maps calculated during the anisotropic refinement. H atoms of the diethoxyphosphoryl group were refined as riding on their parent C atoms. Positional and isotropic displacement parameters of the remaining H's were allowed to refine freely.

Computing details top

Data collection: SMART (Bruker, 2003); cell refinement: SAINT-Plus (Bruker, 2003); data reduction: SAINT-Plus (Bruker, 2003); program(s) used to solve structure: SHELXTL (Bruker, 2003); program(s) used to refine structure: SHELXTL (Bruker, 2003); molecular graphics: SHELXTL (Bruker, 2003); software used to prepare material for publication: SHELXTL (Bruker, 2003).

Figures top
[Figure 1] Fig. 1. View of the molecule. Displacement elipsoids are drawn at the 50% probability level. The C23 methyl group is disordered and was refined over two sites. The picture shows sites for which the occupation factor was 0.825 (5).
[Figure 2] Fig. 2. Newman projection along the C2—P bond.
rac-Diethyl [(1S,2R)-1-(4-bromophenyl)-6-hydroxy-3-oxo-2,3-dihydro-1H- benzo[f]chromen-2-yl]phosphonate top
Crystal data top
C23H22BrO6PF000 = 1032
Mr = 505.29Dx = 1.407 Mg m3
Monoclinic, P21/nMo Kα radiation
λ = 0.71073 Å
a = 12.8328 (5) ÅCell parameters from 7599 reflections
b = 11.7500 (5) Åθ = 2.2–31.1º
c = 15.8477 (7) ŵ = 1.83 mm1
β = 93.1840 (10)ºT = 90 (2) K
V = 2385.91 (17) Å3Prism, colourless
Z = 40.20 × 0.20 × 0.10 mm
Data collection top
Bruker SMART APEX
diffractometer
6239 independent reflections
Radiation source: fine-focus sealed tube5698 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.021
T = 90(2) Kθmax = 29.0º
ω scansθmin = 2.0º
Absorption correction: multi-scan
(SHELXTL; Bruker, 2003)
h = 16→17
Tmin = 0.697, Tmax = 0.839k = 15→15
54317 measured reflectionsl = 21→20
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)] = 0.023H atoms treated by a mixture of
independent and constrained refinement
wR(F2) = 0.064  w = 1/[σ2(Fo2) + (0.0365P)2 + 0.8812P]
where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max = 0.001
6239 reflectionsΔρmax = 0.43 e Å3
341 parametersΔρmin = 0.38 e Å3
Primary atom site location: structure-invariant direct methodsExtinction correction: none
Crystal data top
C23H22BrO6PV = 2385.91 (17) Å3
Mr = 505.29Z = 4
Monoclinic, P21/nMo Kα
a = 12.8328 (5) ŵ = 1.83 mm1
b = 11.7500 (5) ÅT = 90 (2) K
c = 15.8477 (7) Å0.20 × 0.20 × 0.10 mm
β = 93.1840 (10)º
Data collection top
Bruker SMART APEX
diffractometer
6239 independent reflections
Absorption correction: multi-scan
(SHELXTL; Bruker, 2003)
5698 reflections with I > 2σ(I)
Tmin = 0.697, Tmax = 0.839Rint = 0.021
54317 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.023341 parameters
wR(F2) = 0.064H atoms treated by a mixture of
independent and constrained refinement
S = 1.04Δρmax = 0.43 e Å3
6239 reflectionsΔρmin = 0.38 e Å3
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 > 2sigma(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*/UeqOcc. (<1)
Br0.284650 (10)0.133212 (11)0.117426 (9)0.02620 (5)
P0.67307 (2)0.19775 (2)0.525826 (18)0.01323 (6)
O10.44301 (6)0.30270 (7)0.45792 (5)0.01483 (16)
O20.40612 (7)0.14418 (7)0.52698 (6)0.01900 (17)
O30.71414 (6)0.08202 (7)0.56545 (5)0.01764 (17)
O40.64137 (7)0.28582 (7)0.58760 (6)0.02162 (18)
O50.76326 (7)0.23729 (8)0.46864 (6)0.02367 (19)
O60.51248 (8)0.64805 (7)0.31004 (6)0.02113 (18)
H60.4708 (15)0.6687 (17)0.3414 (13)0.037 (5)*
C10.46538 (8)0.19325 (9)0.48278 (7)0.0134 (2)
C20.56568 (8)0.14374 (9)0.45337 (7)0.0125 (2)
H210.5641 (11)0.0631 (13)0.4642 (9)0.013 (3)*
C30.57717 (8)0.16968 (9)0.35592 (7)0.0127 (2)
H310.6466 (12)0.1471 (12)0.3433 (9)0.015 (3)*
C40.56215 (8)0.29631 (9)0.34215 (7)0.0128 (2)
C50.60639 (9)0.35682 (9)0.27266 (7)0.0138 (2)
C60.58971 (9)0.47646 (9)0.26287 (7)0.0154 (2)
C70.52702 (9)0.53432 (9)0.32264 (7)0.0155 (2)
C80.48201 (9)0.47477 (9)0.38750 (7)0.0151 (2)
H810.4406 (13)0.5087 (15)0.4253 (11)0.029 (4)*
C90.50004 (9)0.35658 (9)0.39486 (7)0.0130 (2)
C100.66465 (9)0.29916 (10)0.21058 (8)0.0185 (2)
H1010.6760 (12)0.2190 (14)0.2166 (10)0.023 (4)*
C110.70274 (10)0.35731 (11)0.14187 (8)0.0223 (3)
H1110.7417 (14)0.3187 (16)0.1015 (11)0.031 (4)*
C120.68582 (10)0.47584 (11)0.13268 (8)0.0230 (3)
H1210.7108 (13)0.5141 (15)0.0840 (11)0.030 (4)*
C130.63152 (10)0.53456 (11)0.19212 (8)0.0198 (2)
H1310.6213 (14)0.6112 (16)0.1843 (11)0.029 (4)*
C140.50280 (8)0.09639 (9)0.29837 (7)0.0132 (2)
C150.52697 (9)0.01874 (10)0.28509 (7)0.0174 (2)
H1510.5900 (13)0.0521 (14)0.3119 (11)0.028 (4)*
C160.46203 (10)0.08798 (10)0.23236 (8)0.0192 (2)
H1610.4786 (13)0.1668 (15)0.2241 (11)0.029 (4)*
C170.37239 (9)0.04082 (10)0.19235 (8)0.0182 (2)
C180.34500 (9)0.07230 (10)0.20549 (8)0.0200 (2)
H1810.2817 (15)0.1014 (16)0.1791 (11)0.034 (5)*
C190.41108 (9)0.14036 (10)0.25875 (8)0.0177 (2)
H1910.3946 (12)0.2175 (14)0.2675 (10)0.024 (4)*
C200.80761 (10)0.07514 (11)0.62439 (8)0.0232 (2)
H2010.79040.09940.68180.028*
H2020.86380.12480.60490.028*
C210.84199 (12)0.04818 (12)0.62500 (10)0.0307 (3)
H2110.78400.09670.64060.046*
H2120.90110.05820.66620.046*
H2130.86310.06950.56860.046*
C220.79348 (14)0.35651 (15)0.45674 (12)0.0447 (5)
H2210.72800.39740.44030.054*0.175 (5)
H2220.81610.38490.51370.054*0.175 (5)
H2230.77980.36830.39660.054*0.825 (5)
H2240.75220.40540.49120.054*0.825 (5)
C23A0.8601 (7)0.3928 (8)0.4080 (6)0.035 (3)0.175 (5)
H2310.92770.35680.42240.052*0.175 (5)
H2320.86680.47550.41420.052*0.175 (5)
H2330.83780.37430.34940.052*0.175 (5)
C23B0.91138 (16)0.3623 (2)0.47651 (14)0.0459 (7)0.825 (5)
H2340.94620.30510.44290.069*0.825 (5)
H2350.92660.34730.53680.069*0.825 (5)
H2360.93690.43830.46250.069*0.825 (5)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br0.02545 (7)0.01887 (7)0.03304 (9)0.00433 (4)0.00962 (5)0.00515 (5)
P0.01309 (12)0.01055 (12)0.01589 (14)0.00006 (9)0.00051 (10)0.00060 (10)
O10.0152 (4)0.0130 (4)0.0168 (4)0.0027 (3)0.0054 (3)0.0036 (3)
O20.0181 (4)0.0180 (4)0.0214 (4)0.0010 (3)0.0058 (3)0.0047 (3)
O30.0168 (4)0.0131 (4)0.0222 (4)0.0020 (3)0.0059 (3)0.0002 (3)
O40.0215 (4)0.0166 (4)0.0263 (5)0.0036 (3)0.0034 (3)0.0081 (3)
O50.0178 (4)0.0275 (5)0.0259 (5)0.0091 (3)0.0025 (3)0.0021 (4)
O60.0292 (5)0.0105 (4)0.0240 (5)0.0015 (3)0.0038 (4)0.0033 (3)
C10.0140 (5)0.0131 (5)0.0131 (5)0.0006 (4)0.0003 (4)0.0002 (4)
C20.0125 (5)0.0103 (5)0.0147 (5)0.0002 (4)0.0001 (4)0.0003 (4)
C30.0133 (5)0.0111 (5)0.0139 (5)0.0009 (4)0.0022 (4)0.0003 (4)
C40.0134 (5)0.0109 (5)0.0142 (5)0.0003 (4)0.0011 (4)0.0004 (4)
C50.0132 (5)0.0145 (5)0.0138 (5)0.0024 (4)0.0018 (4)0.0003 (4)
C60.0165 (5)0.0149 (5)0.0149 (5)0.0033 (4)0.0007 (4)0.0010 (4)
C70.0184 (5)0.0110 (5)0.0168 (5)0.0008 (4)0.0014 (4)0.0009 (4)
C80.0179 (5)0.0128 (5)0.0148 (5)0.0027 (4)0.0018 (4)0.0010 (4)
C90.0143 (5)0.0125 (5)0.0124 (5)0.0006 (4)0.0014 (4)0.0020 (4)
C100.0177 (5)0.0185 (5)0.0200 (6)0.0014 (4)0.0061 (4)0.0021 (4)
C110.0206 (6)0.0277 (6)0.0195 (6)0.0056 (5)0.0078 (5)0.0031 (5)
C120.0238 (6)0.0273 (6)0.0185 (6)0.0106 (5)0.0053 (5)0.0029 (5)
C130.0223 (6)0.0181 (6)0.0191 (6)0.0061 (4)0.0012 (4)0.0043 (4)
C140.0154 (5)0.0119 (5)0.0123 (5)0.0004 (4)0.0014 (4)0.0000 (4)
C150.0196 (5)0.0134 (5)0.0188 (5)0.0030 (4)0.0029 (4)0.0007 (4)
C160.0240 (6)0.0118 (5)0.0216 (6)0.0011 (4)0.0014 (5)0.0008 (4)
C170.0197 (5)0.0152 (5)0.0193 (6)0.0042 (4)0.0026 (4)0.0014 (4)
C180.0173 (5)0.0180 (5)0.0241 (6)0.0018 (4)0.0044 (5)0.0003 (4)
C190.0181 (5)0.0129 (5)0.0218 (6)0.0025 (4)0.0014 (4)0.0012 (4)
C200.0201 (5)0.0240 (6)0.0243 (6)0.0013 (5)0.0098 (5)0.0001 (5)
C210.0297 (7)0.0297 (7)0.0316 (7)0.0116 (6)0.0093 (6)0.0027 (6)
C220.0430 (9)0.0416 (9)0.0475 (10)0.0302 (7)0.0147 (8)0.0203 (7)
C23A0.028 (4)0.042 (5)0.035 (5)0.020 (4)0.011 (3)0.001 (4)
C23B0.0330 (10)0.0670 (16)0.0380 (12)0.0320 (10)0.0053 (8)0.0058 (10)
Geometric parameters (Å, °) top
Br—C171.9255 (12)C12—H1210.963 (17)
P—O41.4964 (9)C13—H1310.918 (18)
P—O31.5762 (8)C14—C191.4015 (16)
P—O51.5790 (9)C14—C151.4064 (15)
P—C21.8560 (11)C15—C161.4062 (17)
O1—C11.3708 (13)C15—H1510.976 (17)
O1—C91.4199 (13)C16—C171.3969 (17)
O2—C11.2085 (14)C16—H1610.961 (18)
O3—C201.4810 (14)C17—C181.3935 (16)
O5—C221.4684 (17)C18—C191.4112 (17)
O6—C71.3625 (13)C18—H1810.956 (19)
O6—H60.79 (2)C19—H1910.943 (16)
C1—C21.5096 (15)C20—C211.5146 (19)
C2—C31.5889 (15)C20—H2010.9900
C2—H210.963 (15)C20—H2020.9900
C3—C41.5146 (14)C21—H2110.9800
C3—C141.5452 (15)C21—H2120.9800
C3—H310.961 (15)C21—H2130.9800
C4—C91.3815 (15)C22—C23A1.259 (8)
C4—C51.4526 (15)C22—C23B1.530 (3)
C5—C61.4290 (15)C22—H2210.9900
C5—C101.4379 (15)C22—H2220.9900
C6—C131.4414 (15)C22—H2230.9700
C6—C71.4462 (15)C22—H2240.9699
C7—C81.3948 (15)C23A—H2231.0758
C8—C91.4117 (15)C23A—H2310.9800
C8—H810.914 (17)C23A—H2320.9800
C10—C111.3967 (17)C23A—H2330.9800
C10—H1010.957 (16)C23B—H2340.9800
C11—C121.4158 (19)C23B—H2350.9800
C11—H1110.949 (18)C23B—H2360.9800
C12—C131.3863 (18)
O4—P—O3115.66 (5)C14—C15—H151120.4 (10)
O4—P—O5113.99 (5)C17—C16—C15119.09 (10)
O3—P—O5104.07 (5)C17—C16—H161120.3 (10)
O4—P—C2114.94 (5)C15—C16—H161120.7 (10)
O3—P—C299.90 (5)C18—C17—C16121.24 (11)
O5—P—C2106.75 (5)C18—C17—Br119.10 (9)
C1—O1—C9120.84 (8)C16—C17—Br119.66 (9)
C20—O3—P122.65 (8)C17—C18—C19118.80 (11)
C22—O5—P124.17 (11)C17—C18—H181119.4 (11)
C7—O6—H6107.5 (15)C19—C18—H181121.8 (11)
O2—C1—O1119.06 (10)C14—C19—C18121.39 (10)
O2—C1—C2124.74 (10)C14—C19—H191118.5 (10)
O1—C1—C2116.19 (9)C18—C19—H191120.1 (10)
C1—C2—C3110.67 (9)O3—C20—C21106.36 (10)
C1—C2—P107.08 (7)O3—C20—H201110.5
C3—C2—P115.46 (7)C21—C20—H201110.5
C1—C2—H21107.3 (8)O3—C20—H202110.5
C3—C2—H21111.4 (8)C21—C20—H202110.5
P—C2—H21104.4 (9)H201—C20—H202108.6
C4—C3—C14113.13 (9)C20—C21—H211109.5
C4—C3—C2108.09 (9)C20—C21—H212109.5
C14—C3—C2112.29 (9)H211—C21—H212109.5
C4—C3—H31110.7 (8)C20—C21—H213109.5
C14—C3—H31105.8 (9)H211—C21—H213109.5
C2—C3—H31106.7 (9)H212—C21—H213109.5
C9—C4—C5118.06 (10)C23A—C22—O5126.5 (5)
C9—C4—C3119.30 (9)C23A—C22—C23B54.0 (5)
C5—C4—C3122.56 (9)O5—C22—C23B106.36 (16)
C6—C5—C10118.01 (10)C23A—C22—H221105.7
C6—C5—C4120.09 (10)O5—C22—H221105.7
C10—C5—C4121.87 (10)C23B—C22—H221147.9
C5—C6—C13119.37 (10)C23A—C22—H222105.7
C5—C6—C7118.47 (10)O5—C22—H222105.7
C13—C6—C7122.10 (10)C23B—C22—H22264.0
O6—C7—C8122.75 (10)H221—C22—H222106.1
O6—C7—C6116.21 (10)C23A—C22—H22355.9
C8—C7—C6121.00 (10)O5—C22—H223103.2
C7—C8—C9118.79 (10)C23B—C22—H223108.5
C7—C8—H81122.9 (11)H221—C22—H22364.4
C9—C8—H81118.3 (11)H222—C22—H223151.1
C4—C9—C8123.49 (10)C23A—C22—H224123.8
C4—C9—O1122.29 (9)O5—C22—H224109.6
C8—C9—O1114.09 (9)C23B—C22—H224115.1
C11—C10—C5121.38 (11)H221—C22—H22451.6
C11—C10—H101120.1 (9)H222—C22—H22455.2
C5—C10—H101118.5 (9)H223—C22—H224113.2
C10—C11—C12120.21 (11)C22—C23A—H22348.3
C10—C11—H111120.8 (11)C22—C23A—H231109.5
C12—C11—H111118.9 (11)H223—C23A—H231138.7
C13—C12—C11119.98 (11)C22—C23A—H232109.5
C13—C12—H121120.9 (10)H223—C23A—H232111.1
C11—C12—H121119.1 (10)C22—C23A—H233109.5
C12—C13—C6121.04 (11)H223—C23A—H23363.6
C12—C13—H131118.1 (11)C22—C23B—H234109.5
C6—C13—H131120.9 (11)C22—C23B—H235109.5
C19—C14—C15118.31 (10)H234—C23B—H235109.5
C19—C14—C3122.33 (10)C22—C23B—H236109.5
C15—C14—C3119.36 (10)H234—C23B—H236109.5
C16—C15—C14121.13 (11)H235—C23B—H236109.5
C16—C15—H151118.5 (10)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O6—H6···O4i0.79 (2)1.95 (2)2.737 (1)175 (2)
Symmetry codes: (i) −x+1, −y+1, −z+1.
Selected geometric parameters (Å, °) top
Br—C171.9255 (12)P—C21.8560 (11)
P—O41.4964 (9)O1—C11.3708 (13)
P—O31.5762 (8)O1—C91.4199 (13)
P—O51.5790 (9)O2—C11.2085 (14)
O4—P—O3115.66 (5)O4—P—C2114.94 (5)
O4—P—O5113.99 (5)O3—P—C299.90 (5)
O3—P—O5104.07 (5)O5—P—C2106.75 (5)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O6—H6···O4i0.79 (2)1.95 (2)2.737 (1)175 (2)
Symmetry codes: (i) −x+1, −y+1, −z+1.
references
References top

Bailly, Ch., Bal, Ch., Barbier, P., Combes, S., Finet, J.-P., Hildebrand, M.-P., Peyrot, V. & Wattez, N. (2003). Journal, 46, 5437–5444. [Please provide missing journal title]

Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555–1573.

Boeyens, J. C. A. (1978). J. Cryst. Mol. Struct. 8, 317–320.

Bruker (2003). SAINT-Plus (Version 6.45A), SHELXTL (Version 6.14) and SMART (Version 5.629). Bruker AXS Inc., Madison, Wisconsin, USA.

Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358.

Etter, M. C. (1990). Acc. Chem. Res. 23, 120–126.

Krawczyk, H., Albrecht, Ł., Wojciechowski, J. & Wolf, W. M. (2007). preparation. [Any update?]

Roelens, F., Huvaere, K., Dhooge, W., Van Cleemput, M., Comhaire, F. & De Keukeleire, D. (2005). Eur. J. Med. Chem. 40, 1042–1051.

Zhang, X., Wang, H., Song, Y., Nie, L., Wang, L., Liu, B., Shen, P. & Liu, Y. (2006). Bioorg. Med. Chem. Lett. 16, 949–953.