Methyl [hydr-oxy(phen-yl)phosphono-meth-yl]phospho-nate methanol solvate.

The title compound, C(8)H(12)O(7)P(2)·CH(4)O, is a monoesterified bis-phospho-nate (or 1-hydroxy-methyl-ene-1,1-bis-phospho-nic acid). These synthetic compounds are widely used in medicine to inhibit bone resorption in diseases like osteoporosis, and are characterized by a stable P-C-P group and are thus analogs of inorganic pyrophosphate. By masking one or several ionizable groups, introduced as phosphono-ester, it was anti-cipated the formation of prodrugs with higher lipophilicity that could facilitate the drug delivery and metabolization. Mol-ecules are paired by inter-molecular hydrogen bonds involving the phospho-nic groups. In addition, dimers are connected side-by-side, building infinite ribbons along the a-axis direction; these ribbons are cross-linked perpendicularly along the b-axis direction via a methanol solvent mol-ecule (disordered over two sites with occupancy factors ca 0.6 and 0.4), forming an extended inter-molecular hydrogen-bonded network. The H atoms of the methyl group in the main molecule are disordered equally over two positions.

Related literature

For related literature, see: Barbey et al. (2003 ▶), Migianu et al. (2005 ▶), Fleisch (1998 ▶, 2002 ▶); Clezardin et al. (2003 ▶); Green & Clezardin (2002 ▶); Lecouvey et al. (2003a ▶,b ▶); Vepsalainen (2002 ▶).

Experimental

Crystal data

C8H12O7P2·CH4O

M = 314.16

Monoclinic,

a = 6.3085 (5) Å

b = 6.9871 (6) Å

c = 28.147 (2) Å

β = 92.654 (3)°

V = 1239.34 (17) Å3

Z = 4

Mo Kα radiation

μ = 0.39 mm−1

T = 293 (2) K

0.30 × 0.20 × 0.20 mm

Data collection

Nonius KappaCCD diffractometer

Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997 ▶) T min = 0.847, T max = 0.929

3837 measured reflections

2375 independent reflections

1943 reflections with I > 2σ(I)

R int = 0.033

Refinement

R[F 2 > 2σ(F 2)] = 0.057

wR(F 2) = 0.141

S = 1.08

2375 reflections

191 parameters

32 restraints

H-atom parameters constrained

Δρmax = 0.56 e Å−3

Δρmin = −0.44 e Å−3

Data collection: COLLECT (Hooft, 1998 ▶); cell refinement: HKL (Otwinowski & Minor, 1997 ▶); data reduction: COLLECT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶) and PLATON (Spek (2003 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶) and CrystalBuilder (Welter, 2006 ▶).

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053680802285X/pk2106sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S160053680802285X/pk2106Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C8H12O7P2·CH4O	Z = 4
Mr = 314.16	F(000) = 656
Monoclinic, P21/c	Dx = 1.684 Mg m−3
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71073 Å
a = 6.3085 (5) Å	θ = 0.4–26.0°
b = 6.9871 (6) Å	µ = 0.39 mm−1
c = 28.147 (2) Å	T = 293 K
β = 92.654 (3)°	Parallelepiped, colourless
V = 1239.34 (17) Å3	0.30 × 0.20 × 0.20 mm

Nonius KappaCCD diffractometer	2375 independent reflections
Radiation source: fine-focus sealed tube	1943 reflections with I > 2σ(I)
graphite	Rint = 0.033
Detector resolution: 9 pixels mm-1	θmax = 25.9°, θmin = 3.3°
φ and ω scans	h = −7→7
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997)	k = −7→8
Tmin = 0.847, Tmax = 0.929	l = −34→34
3837 measured reflections

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.057	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.142	H-atom parameters constrained
S = 1.08	w = 1/[σ2(Fo2) + (0.0456P)2 + 3.3095P] where P = (Fo2 + 2Fc2)/3
2375 reflections	(Δ/σ)max < 0.001
191 parameters	Δρmax = 0.56 e Å−3
32 restraints	Δρmin = −0.44 e Å−3

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	Occ. (<1)
P1	0.41077 (14)	0.23600 (13)	0.08924 (3)	0.0240 (3)
O11	0.4358 (4)	0.3030 (4)	0.03727 (9)	0.0317 (6)
H11	0.3700	0.2305	0.0190	0.047*
O12	0.2224 (4)	0.1143 (4)	0.09548 (10)	0.0371 (7)
O13	0.4134 (4)	0.4188 (4)	0.12031 (9)	0.0340 (6)
H13	0.4428	0.5116	0.1040	0.051*
P2	0.68094 (15)	−0.12727 (14)	0.07691 (3)	0.0273 (3)
O21	0.4976 (4)	−0.2548 (4)	0.08552 (11)	0.0410 (7)
H21	0.3883	−0.1912	0.0851	0.061*	0.50
O22	0.7272 (5)	−0.0849 (4)	0.02594 (9)	0.0394 (7)
H22	0.6239	−0.0328	0.0127	0.059*	0.50
O23	0.8962 (4)	−0.2125 (4)	0.09820 (10)	0.0377 (7)
C23	0.9189 (8)	−0.3297 (7)	0.14094 (17)	0.0532 (12)
H23A	1.0653	−0.3639	0.1466	0.080*	0.50
H23B	0.8352	−0.4438	0.1368	0.080*	0.50
H23C	0.8711	−0.2588	0.1676	0.080*	0.50
H23D	0.7825	−0.3471	0.1541	0.080*	0.50
H23E	1.0126	−0.2672	0.1639	0.080*	0.50
H23F	0.9766	−0.4522	0.1330	0.080*	0.50
C1A	0.5094 (7)	−0.0159 (6)	0.18502 (14)	0.0360 (9)
H1A	0.3840	−0.0484	0.1683	0.043*
C2A	0.5336 (8)	−0.0566 (7)	0.23324 (15)	0.0455 (11)
H2A	0.4235	−0.1146	0.2487	0.055*
C3A	0.7199 (8)	−0.0115 (7)	0.25829 (14)	0.0464 (11)
H3A	0.7371	−0.0416	0.2904	0.056*
C4A	0.8802 (7)	0.0784 (7)	0.23536 (15)	0.0454 (11)
H4A	1.0056	0.1096	0.2523	0.054*
C5A	0.8572 (6)	0.1230 (6)	0.18731 (13)	0.0341 (9)
H5A	0.9657	0.1861	0.1724	0.041*
C6A	0.6723 (6)	0.0736 (5)	0.16151 (12)	0.0259 (8)
C7	0.6573 (5)	0.1066 (5)	0.10757 (12)	0.0223 (7)
O7	0.8204 (4)	0.2294 (4)	0.09186 (8)	0.0267 (6)
H7	0.9357	0.1761	0.0958	0.040*
O62	0.1603 (6)	0.8597 (7)	0.04096 (16)	0.0193 (14)	0.559 (10)
C61	0.159 (5)	0.695 (3)	0.0135 (8)	0.072 (6)	0.559 (10)
O72	0.1408 (11)	0.5812 (12)	−0.0056 (3)	0.037 (2)	0.441 (10)
C71	0.167 (5)	0.754 (4)	0.0172 (13)	0.067 (7)	0.441 (10)

	U11	U22	U33	U12	U13	U23
P1	0.0226 (5)	0.0195 (5)	0.0300 (5)	0.0013 (4)	0.0009 (3)	0.0004 (4)
O11	0.0375 (14)	0.0296 (14)	0.0274 (13)	0.0005 (12)	−0.0040 (10)	−0.0004 (11)
O12	0.0213 (13)	0.0321 (15)	0.0580 (18)	−0.0016 (12)	0.0036 (11)	0.0031 (14)
O13	0.0476 (16)	0.0214 (14)	0.0335 (14)	0.0038 (12)	0.0075 (12)	−0.0028 (11)
P2	0.0311 (5)	0.0191 (5)	0.0314 (5)	0.0023 (4)	−0.0027 (4)	−0.0039 (4)
O21	0.0399 (16)	0.0255 (14)	0.0571 (19)	−0.0008 (13)	−0.0027 (13)	−0.0066 (13)
O22	0.0545 (17)	0.0334 (16)	0.0300 (14)	0.0042 (14)	−0.0012 (12)	−0.0061 (12)
O23	0.0381 (15)	0.0328 (16)	0.0419 (16)	0.0107 (13)	−0.0008 (12)	0.0005 (13)
C23	0.065 (3)	0.042 (3)	0.052 (3)	0.013 (2)	−0.014 (2)	0.002 (2)
C1A	0.039 (2)	0.032 (2)	0.037 (2)	−0.0049 (19)	0.0036 (17)	0.0032 (18)
C2A	0.060 (3)	0.037 (2)	0.041 (2)	−0.006 (2)	0.015 (2)	0.006 (2)
C3A	0.073 (3)	0.043 (3)	0.024 (2)	0.004 (2)	0.002 (2)	0.0043 (19)
C4A	0.053 (3)	0.049 (3)	0.033 (2)	0.003 (2)	−0.0079 (19)	−0.002 (2)
C5A	0.035 (2)	0.033 (2)	0.034 (2)	−0.0004 (18)	0.0001 (16)	−0.0016 (17)
C6A	0.0329 (19)	0.0182 (17)	0.0267 (18)	0.0032 (15)	0.0028 (14)	−0.0003 (14)
C7	0.0192 (16)	0.0193 (17)	0.0286 (17)	−0.0045 (14)	0.0022 (13)	0.0002 (14)
O7	0.0219 (12)	0.0242 (13)	0.0341 (14)	−0.0034 (11)	0.0015 (10)	0.0061 (11)
O62	0.012 (2)	0.016 (3)	0.029 (3)	−0.0013 (18)	−0.0002 (16)	−0.0083 (19)
C61	0.094 (14)	0.066 (16)	0.057 (10)	0.005 (12)	0.004 (9)	0.026 (10)
O72	0.035 (4)	0.031 (4)	0.046 (4)	−0.006 (3)	−0.003 (3)	−0.003 (3)
C71	0.043 (9)	0.054 (15)	0.105 (15)	−0.015 (10)	0.011 (9)	−0.003 (13)

P1—O12	1.478 (3)	C23—H23F	0.9600
P1—O13	1.548 (3)	C1A—C2A	1.388 (6)
P1—O11	1.551 (3)	C1A—C6A	1.396 (5)
P1—C7	1.851 (3)	C1A—H1A	0.9300
O11—H11	0.8200	C2A—C3A	1.379 (7)
O13—H13	0.8200	C2A—H2A	0.9300
P2—O21	1.489 (3)	C3A—C4A	1.376 (6)
P2—O22	1.507 (3)	C3A—H3A	0.9300
P2—O23	1.575 (3)	C4A—C5A	1.389 (6)
P2—C7	1.857 (4)	C4A—H4A	0.9300
O21—H21	0.8200	C5A—C6A	1.389 (5)
O22—H22	0.8200	C5A—H5A	0.9300
O23—C23	1.457 (5)	C6A—C7	1.534 (5)
C23—H23A	0.9600	C7—O7	1.426 (4)
C23—H23B	0.9600	O7—H7	0.8200
C23—H23C	0.9600	O62—C61	1.384 (18)
C23—H23D	0.9600	O72—C71	1.37 (2)
C23—H23E	0.9600
O12—P1—O13	113.27 (16)	O23—C23—H23F	109.5
O12—P1—O11	113.79 (16)	H23A—C23—H23F	56.3
O13—P1—O11	106.55 (15)	H23B—C23—H23F	56.3
O12—P1—C7	110.81 (16)	H23C—C23—H23F	141.1
O13—P1—C7	105.00 (15)	H23D—C23—H23F	109.5
O11—P1—C7	106.82 (15)	H23E—C23—H23F	109.5
P1—O11—H11	109.5	C2A—C1A—C6A	120.4 (4)
P1—O13—H13	109.5	C2A—C1A—H1A	119.8
O21—P2—O22	117.32 (17)	C6A—C1A—H1A	119.8
O21—P2—O23	111.97 (16)	C3A—C2A—C1A	120.4 (4)
O22—P2—O23	103.58 (16)	C3A—C2A—H2A	119.8
O21—P2—C7	111.78 (16)	C1A—C2A—H2A	119.8
O22—P2—C7	107.03 (16)	C4A—C3A—C2A	119.5 (4)
O23—P2—C7	104.03 (15)	C4A—C3A—H3A	120.3
P2—O21—H21	109.5	C2A—C3A—H3A	120.3
P2—O22—H22	109.5	C3A—C4A—C5A	120.9 (4)
C23—O23—P2	125.2 (3)	C3A—C4A—H4A	119.6
O23—C23—H23A	109.5	C5A—C4A—H4A	119.6
O23—C23—H23B	109.5	C6A—C5A—C4A	120.0 (4)
H23A—C23—H23B	109.5	C6A—C5A—H5A	120.0
O23—C23—H23C	109.5	C4A—C5A—H5A	120.0
H23A—C23—H23C	109.5	C5A—C6A—C1A	118.9 (3)
H23B—C23—H23C	109.5	C5A—C6A—C7	119.5 (3)
O23—C23—H23D	109.5	C1A—C6A—C7	121.5 (3)
H23A—C23—H23D	141.1	O7—C7—C6A	112.6 (3)
H23B—C23—H23D	56.3	O7—C7—P1	103.2 (2)
H23C—C23—H23D	56.3	C6A—C7—P1	111.2 (2)
O23—C23—H23E	109.5	O7—C7—P2	108.1 (2)
H23A—C23—H23E	56.3	C6A—C7—P2	109.0 (2)
H23B—C23—H23E	141.1	P1—C7—P2	112.63 (17)
H23C—C23—H23E	56.3	C7—O7—H7	109.5
H23D—C23—H23E	109.5
O21—P2—O23—C23	−32.5 (4)	O13—P1—C7—O7	−66.9 (2)
O22—P2—O23—C23	−159.8 (3)	O11—P1—C7—O7	46.0 (2)
C7—P2—O23—C23	88.4 (3)	O12—P1—C7—C6A	−68.5 (3)
C6A—C1A—C2A—C3A	−0.9 (7)	O13—P1—C7—C6A	54.1 (3)
C1A—C2A—C3A—C4A	1.5 (7)	O11—P1—C7—C6A	167.0 (2)
C2A—C3A—C4A—C5A	−0.4 (7)	O12—P1—C7—P2	54.2 (2)
C3A—C4A—C5A—C6A	−1.3 (7)	O13—P1—C7—P2	176.81 (17)
C4A—C5A—C6A—C1A	1.9 (6)	O11—P1—C7—P2	−70.3 (2)
C4A—C5A—C6A—C7	−174.2 (4)	O21—P2—C7—O7	−171.4 (2)
C2A—C1A—C6A—C5A	−0.8 (6)	O22—P2—C7—O7	−41.7 (3)
C2A—C1A—C6A—C7	175.2 (4)	O23—P2—C7—O7	67.6 (2)
C5A—C6A—C7—O7	−14.6 (5)	O21—P2—C7—C6A	65.9 (3)
C1A—C6A—C7—O7	169.4 (3)	O22—P2—C7—C6A	−164.4 (2)
C5A—C6A—C7—P1	−129.9 (3)	O23—P2—C7—C6A	−55.1 (3)
C1A—C6A—C7—P1	54.1 (4)	O21—P2—C7—P1	−58.0 (2)
C5A—C6A—C7—P2	105.4 (3)	O22—P2—C7—P1	71.7 (2)
C1A—C6A—C7—P2	−70.6 (4)	O23—P2—C7—P1	−179.03 (17)
O12—P1—C7—O7	170.5 (2)

D—H···A	D—H	H···A	D···A	D—H···A
O13—H13···O21i	0.82	1.75	2.548 (4)	163.
O11—H11···O22ii	0.82	1.72	2.525 (4)	169.
O21—H21···O62iii	0.82	1.89	2.548 (5)	136.
O7—H7···O12iv	0.82	1.86	2.658 (3)	164.

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O13—H13⋯O21i	0.82	1.75	2.548 (4)	163
O11—H11⋯O22ii	0.82	1.72	2.525 (4)	169
O21—H21⋯O62iii	0.82	1.89	2.548 (5)	136
O7—H7⋯O12iv	0.82	1.86	2.658 (3)	164

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .