Ethyl (2-pyridyl­methyl)­phospho­nate

Molecules of the title compound, C₈H₁₂NO₃P, exist as zwitterions. The positive charge formally located on the N atom is spread over the pyridyl ring. A partial delocalization of negative charge within the O-P-O system is observed. The conformational features and hydrogen-bonding network of the title compound are compared with the structure of (2-pyridyl­methyl)­phosphonic acid.

S1. Comment

Coordination compounds of Pt^II (cisplatin, carboplatin and oxaliplatin) are widely use in antitumor therapy (Reedijk, 2003; Judson & Kelland, 2000). Platinum aminophosphonate complexes show particular activity against bone malignancies (Bloemink et al., 1999; Galanski et al., 1999), since phosphonic acids derivatives display a high affinity to bone tissue (Klenner et al., 1990). Analogs of cisplatin, platinum(II) complexes containing diethyl pyridylmethylphosphonates have shown antitumor activity against Sarcoma Sa 180 in mice (Aranowska et al., 2004), and are also capable of activating in vivo mast cells (Brzezińska-Błaszczyk et al., 1996) and affecting in vitro blood platelet aggregation (Kostka & Ochocki, 1996).

Following our work on the synthesis and structure determination of pyridylmethylphosphonate derivatives as novel ligands (Chęcińska et al., 2002) for antineoplastic platinum(II) complexes (Chęcińska et al., 2003), the title compound, C₈H₁₂NO₃P, (I), was synthesized and an X-ray diffraction study was undertaken. We compare the results with the crystal structure of 2-pyridylmethylphosphonic acid, C₆H₈NO₃P, (II) (Gałdecki & Wolf, 1990). The Cambridge Structural Database (CSD; Version 5.25; Allen, 2002) contains many structures of diethyl pyridylmethylphosphonates (especially as ligands in metal complexes) but no structure of a monoester of pyridylmethylphosphonate.

Molecules of aminophosphonic acids usually exists as zwitterions, as does (I). The N atom is protonated and the positive charge formally located on this N atom is spread over the pyridyl ring. The significant difference between the P1—O1 and P1—O3 bond distances (Table 1) may indicate a partial delocalization of negative charge within the O≐P≐O system. These phosphorus–oxygen bond lengths differ significantly from the corresponding values of 1.507 (3) and 1.500 (4) Å, and 1.506 (2) and 1.5039 (14) Å, observed for (II) (Gałdecki & Wolf, 1990), and 4-pyridylmethylphosphonic acid (Gałdecki & Wolf, 1996), respectively. On the other hand, the P1—O1 and P1—O3 distances are similar to those found in the structure of 3-pyridylmethylphosphonic acid [1.4860 (18) and 1.515 (17) Å; Chęcińska et al., 2002]. It is interesting to compare the overall orientations of the molecules of (I) and (II). While the two molecules have essentially similar conformations, they differ in the positioning of the N atom with regard to the phosphonate group (Fig. 2). The orientation of the linking C atom causes a `reversed' conformation (Table 3). In both structures, the P atom has tetrahedral geometry (distorted towards trigonal pyramidal), with an elongated P1—C1 apical bond. It seems that two effects may influence the angular deformation of these PO₃C tetrahedra, viz. their molecular structural differences and/or intermolecular interactions.

The crystal-packing arrangements in crystals of (I) and (II) are as follows. The hydrogen-bonding network in (I) is different from that in (II) (Figs. 3 and 4), resulting in part from the absence of aromatic π–π interactions between the pyridyl rings in (I). Moreover, the N1—H1···O1(1 − x, 1 − y, 1 − z) hydrogen bond is responsible for the formation of a cyclic dimer about a centre of symmetry; an R₂²(12) graph-set descriptor (Bernstein et al., 1995) is generated. Additionally, the crystal structure is dominated by a network of weak intermolecular C—H···O interactions. The three interactions (Table 2) produce a pattern whose first-level descriptor is C(7), C(4) and C(6), respectively. This combination of N—H···O and C—H···O hydrogen bonds links the molecules into a three-dimensional network. In structure (I), a weak intermolecular C—H···π interaction is also observed, whereas this type of interaction is not found in (II).

In (II), atom N1 is involved in an almost linear intermolecular N1—H2···O3 interaction (Table 4). Propagation of this contact produces a chain running along [001], which can be described by the C(6) motif (Bernstein et al., 1995). A short intermolecular contact of 2.559 (5) Å between atoms O1 and O2(1 − x, −y, 1 − z) is also observed. The packing of (II) involves two weak C—H···O interactions (Table 4), which link the molecules to form infinite chains running parallel to the [001] direction; for both, the first-level graph-set descriptor is C(7). All three chains are organized into closely packed layers, perpendicular to the a axis. Neighbouring layers are further connected via π–π stacking interactions between the pyridyl rings, with an interplanar spacing of 3.49 Å [the centroid separation is 3.623 (3) Å].

Cg is the centroid of the pyridyl ring.

S2. Experimental

The title compound was prepared by dealkylation of one of the ester groups in diethyl pyridin-2-ylmethylphosphonate using hydrobromic acid in glacial acetic acid. Diethyl pyridin-2-ylmetylphosphonate was prepared according to the procedures described in the literature (Kostka & Ochocki, 1983). To diethyl pyridin-2-ylmetylphosphonate (1.50 g, 6.60 mmol) was added 33% hydrobromic acid in glacial acetic acid and the mixture was stirred at room temperature for 2 h. The reaction was carried out in dry conditions. The excess of HBr and CH₃COOH was then evaporated under reduced pressure, the residue was dissolved in water (8 ml) and NaHCO₃ was added until the pH of the mixture was neutral. The solution was evaporated to dryness and ethanol (10 ml) was added. After filtration, ethanol was evaporated. The oil residue was dissolved in water (20 ml) and extracted with chloroform (3 × 20 ml). The water solution was evaporated to a volume of 5 ml and applied onto a column of Dowex 50 W × 4 (H⁺ form; 20 ml). Fractions were checked via thin layer chromatography [eluant i-propanol/NH3_aq/H₂O (8:1:1)]. Collected fractions were evaporated to dryness, and dry ethanol (10 ml) was added to the residue, the precipitate was filtered off and the solvent was evaporated to dryness (yield 62%). Diffraction-quality crystals of (I) were obtained from ethanol by slow evaporation of the solvent at room temperature (m.p. 451–452 K).

S3. Refinement

All H atoms were placed in idealized positions (C—H = 0.93–0.97 Å and N—H = 0.86 Å) and constrained to ride on their parent atoms, with U_iso(H) values of 1.2 U_eq(C,N) [or 1.5 U_eq(C_methyl)].

Computing details

Data collection: MSC/AFC Diffractometer Control Software (Molecular Structure Corporation, 1989); cell refinement: MSC/AFC Diffractometer Control Software; data reduction: CrystalStructure (Rigaku/MSC, 2002); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2001); software used to prepare material for publication: PLATON.

Figures

	Fig. 1. The structure of the title compound, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 40% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. A comparison of the molecular conformations of (I) and (II).
	Fig. 3. The hydrogen-bonding network in (I). P, O and N atoms are shaded. Dashed lines indicate hydrogen bonds and weak interactions.
	Fig. 4. The hydrogen-bonding network in (II), using the same conventions as Fig. 3.

Ethyl (2-pyridylmethyl)phosphonate

Crystal data

C8H12NO3P	F(000) = 424
Mr = 201.16	Dx = 1.431 Mg m^−3
Monoclinic, P21/c	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ybc	Cell parameters from 25 reflections
a = 8.7169 (5) Å	θ = 33.1–37.2°
b = 11.2997 (5) Å	µ = 2.44 mm^−1
c = 9.7940 (5) Å	T = 293 K
β = 104.534 (4)°	Prism, colourless
V = 933.82 (8) Å^3	0.30 × 0.30 × 0.15 mm
Z = 4

Data collection

Rigaku AFC-5S diffractometer	1268 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.018
Graphite monochromator	θmax = 70.0°, θmin = 5.2°
ω scan	h = −8→10
Absorption correction: analytical (de Meulenaer & Tompa, 1965)	k = −2→13
Tmin = 0.535, Tmax = 0.702	l = −11→11
1849 measured reflections	3 standard reflections every 150 reflections
1743 independent reflections	intensity decay: 1.9%

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)] = 0.046	H-atom parameters constrained
wR(F^2) = 0.134	w = 1/[σ^2(Fo^2) + (0.0819P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.02	(Δ/σ)max < 0.001
1743 reflections	Δρmax = 0.36 e Å^−3
119 parameters	Δρmin = −0.41 e Å^−3
0 restraints	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.025 (2)

Special details

Experimental. Spectroscopic analysis, IR (ν, cm⁻¹): 1655 (aromatic C═C, C═N), 1232–1202 (P═O), 1051 (P—O—C); ¹H NMR (D₂O, δ, p.p.m.): 1.19 (t, 3H, ³J_HH = 7.10 Hz, CH₃—CH₂O), 3.52 (d, 2H, ²J_HP = 20.61 Hz, CH₂—P), 3.90 (dq, 2H, ³J_HH = 7.10 Hz, POCH₂—CH₃), 7.85–7.93 (m, 2H, aromatic H—C3, H—C5), 8.45–8.51 (m, 1H, aromatic H—C4), 8.62 (d, 1H, ³J_HH = 5.61 Hz, aromatic H—C6); ³¹P NMR (D₂O, δ, p.p.m.): 15.66.

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
P1	0.68878 (8)	0.34585 (6)	0.46363 (8)	0.0373 (3)
O1	0.6125 (2)	0.40058 (17)	0.5687 (2)	0.0437 (5)
O2	0.6834 (2)	0.20714 (17)	0.4955 (2)	0.0465 (6)
C7	0.7761 (4)	0.1250 (3)	0.4418 (4)	0.0540 (8)
H7A	0.8837	0.1543	0.4565	0.065*
H7B	0.7321	0.1143	0.3413	0.065*
C8	0.7765 (4)	0.0070 (3)	0.5185 (3)	0.0649 (10)
H8A	0.8182	0.0187	0.6181	0.097*
H8B	0.8414	−0.0489	0.4848	0.097*
H8C	0.6701	−0.0227	0.5009	0.097*
O3	0.8466 (2)	0.3873 (2)	0.4569 (2)	0.0528 (6)
C1	0.5555 (3)	0.3642 (2)	0.2890 (3)	0.0414 (7)
H11	0.5527	0.4474	0.2640	0.050*
H12	0.5990	0.3214	0.2215	0.050*
C2	0.3891 (3)	0.3228 (2)	0.2749 (3)	0.0374 (6)
C3	0.3268 (3)	0.2197 (3)	0.2037 (3)	0.0431 (7)
H3	0.3903	0.1708	0.1645	0.052*
C4	0.1700 (4)	0.1910 (3)	0.1921 (3)	0.0527 (8)
H4	0.1266	0.1230	0.1442	0.063*
C5	0.0771 (4)	0.2651 (3)	0.2528 (3)	0.0501 (8)
H5	−0.0293	0.2478	0.2440	0.060*
C6	0.1429 (3)	0.3618 (3)	0.3241 (3)	0.0473 (8)
H6	0.0832	0.4097	0.3684	0.057*
N1	0.2954 (3)	0.3896 (2)	0.3317 (2)	0.0400 (6)
H1	0.3338	0.4533	0.3751	0.048*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
P1	0.0308 (4)	0.0392 (4)	0.0411 (4)	0.0013 (3)	0.0075 (3)	−0.0005 (3)
O1	0.0449 (11)	0.0441 (12)	0.0432 (11)	0.0049 (9)	0.0130 (9)	−0.0059 (9)
O2	0.0500 (12)	0.0348 (12)	0.0574 (13)	0.0080 (9)	0.0186 (10)	0.0018 (9)
C7	0.063 (2)	0.0477 (19)	0.0524 (19)	0.0142 (15)	0.0171 (16)	−0.0023 (15)
C8	0.078 (2)	0.0426 (19)	0.072 (2)	0.0155 (17)	0.0139 (19)	0.0029 (17)
O3	0.0281 (10)	0.0626 (14)	0.0659 (15)	−0.0045 (9)	0.0087 (9)	0.0011 (11)
C1	0.0344 (14)	0.0480 (17)	0.0431 (15)	−0.0037 (12)	0.0119 (12)	0.0007 (13)
C2	0.0328 (13)	0.0405 (16)	0.0372 (14)	0.0023 (11)	0.0055 (11)	0.0025 (12)
C3	0.0446 (16)	0.0426 (17)	0.0408 (16)	0.0021 (13)	0.0081 (12)	−0.0025 (13)
C4	0.0486 (18)	0.0537 (19)	0.0508 (19)	−0.0102 (15)	0.0032 (14)	−0.0021 (15)
C5	0.0353 (15)	0.065 (2)	0.0484 (18)	−0.0083 (14)	0.0066 (13)	0.0027 (15)
C6	0.0335 (14)	0.060 (2)	0.0482 (17)	0.0069 (14)	0.0094 (13)	0.0028 (14)
N1	0.0342 (12)	0.0436 (13)	0.0407 (13)	0.0024 (10)	0.0063 (10)	−0.0039 (10)

Geometric parameters (Å, º)

P1—O3	1.4702 (19)	C1—H12	0.9700
P1—O1	1.4925 (19)	C2—N1	1.332 (3)
P1—O2	1.601 (2)	C2—C3	1.396 (4)
P1—C1	1.822 (3)	C3—C4	1.382 (4)
O2—C7	1.416 (3)	C3—H3	0.9300
C7—C8	1.530 (4)	C4—C5	1.398 (4)
C7—H7A	0.9700	C4—H4	0.9300
C7—H7B	0.9700	C5—C6	1.345 (4)
C8—H8A	0.9600	C5—H5	0.9300
C8—H8B	0.9600	C6—N1	1.349 (3)
C8—H8C	0.9600	C6—H6	0.9300
C1—C2	1.498 (4)	N1—H1	0.8600
C1—H11	0.9700
O3—P1—O1	118.85 (13)	C2—C1—H12	108.5
O3—P1—O2	113.22 (12)	P1—C1—H12	108.5
O1—P1—O2	103.37 (11)	H11—C1—H12	107.5
O3—P1—C1	107.73 (13)	N1—C2—C3	118.6 (3)
O1—P1—C1	108.12 (12)	N1—C2—C1	117.8 (2)
O2—P1—C1	104.58 (12)	C3—C2—C1	123.6 (3)
C7—O2—P1	121.44 (19)	C4—C3—C2	119.3 (3)
O2—C7—C8	108.6 (3)	C4—C3—H3	120.3
O2—C7—H7A	110.0	C2—C3—H3	120.3
C8—C7—H7A	110.0	C3—C4—C5	119.5 (3)
O2—C7—H7B	110.0	C3—C4—H4	120.3
C8—C7—H7B	110.0	C5—C4—H4	120.3
H7A—C7—H7B	108.3	C6—C5—C4	119.3 (3)
C7—C8—H8A	109.5	C6—C5—H5	120.3
C7—C8—H8B	109.5	C4—C5—H5	120.3
H8A—C8—H8B	109.5	C5—C6—N1	120.2 (3)
C7—C8—H8C	109.5	C5—C6—H6	119.9
H8A—C8—H8C	109.5	N1—C6—H6	119.9
H8B—C8—H8C	109.5	C2—N1—C6	123.0 (3)
C2—C1—P1	115.16 (19)	C2—N1—H1	118.5
C2—C1—H11	108.5	C6—N1—H1	118.5
P1—C1—H11	108.5
O3—P1—O2—C7	−35.1 (3)	N1—C2—C3—C4	1.1 (4)
O1—P1—O2—C7	−165.1 (2)	C1—C2—C3—C4	−177.7 (3)
C1—P1—O2—C7	81.9 (2)	C2—C3—C4—C5	−0.6 (4)
P1—O2—C7—C8	166.3 (2)	C3—C4—C5—C6	−1.4 (5)
O3—P1—C1—C2	178.3 (2)	C4—C5—C6—N1	2.8 (5)
O1—P1—C1—C2	−52.1 (2)	C3—C2—N1—C6	0.4 (4)
O2—P1—C1—C2	57.5 (2)	C1—C2—N1—C6	179.2 (3)
P1—C1—C2—N1	74.7 (3)	C5—C6—N1—C2	−2.4 (4)
P1—C1—C2—C3	−106.6 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1^i	0.86	1.77	2.612 (3)	168
C6—H6···O3^ii	0.93	2.44	3.183 (3)	137
C3—H3···O1^iii	0.93	2.49	3.384 (3)	161
C1—H12···O2^iii	0.97	2.52	3.430 (3)	156
C8—H8B···Cg^iv	0.96	2.96	3.663 (3)	131

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) x−1, y, z; (iii) x, −y+1/2, z−1/2; (iv) −x+1, y−1/2, −z+1/2.