Diethyl [2,2,2-trifluoro-1-phenyl­sulfonyl­amino-1-(trifluoro­meth­yl)eth­yl]phospho­nate

Sanjeeva J Wijeyesakere; Faik A Nasser; Jeff W Kampf; Alexey Y Aksinenko; Vladimir B Sokolov; Vladimir V Malygin; Galina F Makhaeva; Rudy J Richardson

doi:10.1107/S1600536808020175

. 2008 Jul 5;64(Pt 8):o1425. doi: 10.1107/S1600536808020175

Diethyl [2,2,2-trifluoro-1-phenylsulfonylamino-1-(trifluoromethyl)ethyl]phosphonate

Sanjeeva J Wijeyesakere ^a, Faik A Nasser ^a, Jeff W Kampf ^b, Alexey Y Aksinenko ^c, Vladimir B Sokolov ^c, Vladimir V Malygin ^c,^‡, Galina F Makhaeva ^c, Rudy J Richardson ^a,^*

PMCID: PMC2600860 NIHMSID: NIHMS63776 PMID: 19079747

Abstract

The title compound, C₁₃H₁₆F₆NO₅PS, is of interest with respect to inhibition of serine hydrolases. Its structure contains a 1.8797 (13) Å P—C bond and two intermolecular N—H⋯O=P hydrogen bonds, resulting in centrosymmetric dimers. An intramolecular N—H⋯O=P hydrogen bond is also present.

Related literature

For related literature, see: Chekhlov et al. (1995 ▶); Makhaeva et al. (2005 ▶); Adams et al. (2008 ▶); Chen et al. (2008 ▶); Guo et al. (2008 ▶); Kachkovskyi & Kolodiazhnyi (2007 ▶); Liu et al. (1995 ▶).

Experimental

Crystal data

C₁₃H₁₆F₆NO₅PS
M _r = 443.3
Monoclinic,
a = 11.6913 (15) Å
b = 10.1375 (13) Å
c = 15.5955 (19) Å
β = 93.264 (2)°
V = 1845.4 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.34 mm⁻¹
T = 113 (2) K
0.60 × 0.42 × 0.40 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2003 ▶) T _min = 0.820, T _max = 0.874
20001 measured reflections
4568 independent reflections
4027 reflections with I > 2σ(I)
R _int = 0.022

Refinement

R[F ² > 2σ(F ²)] = 0.029
wR(F ²) = 0.082
S = 1.03
4568 reflections
246 parameters
H-atom parameters constrained
Δρ_max = 0.34 e Å⁻³
Δρ_min = −0.33 e Å⁻³

Data collection: SMART (Bruker, 1998 ▶); cell refinement: SAINT (Bruker, 2003 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808020175/si2094sup1.cif

e-64-o1425-sup1.cif^{(19KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808020175/si2094Isup2.hkl

e-64-o1425-Isup2.hkl^{(223.8KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯O3	0.88	2.34	2.8730 (14)	119
N1—H1A⋯O3ⁱ	0.88	2.00	2.8324 (14)	158

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank NIH (ES07062), CRDF (RB2-2035 and RB2-2488) and ARO (DAAD19-02-1-0388) for financial support.

supplementary crystallographic information

Comment

The title compound is a member of the fluorinated α-aminophosphonate (FAP) group of compounds [(RO)₂P(O)C(CF₃)₂NHS(O)₂C₆H₅; R = CH₃, C₂H₅, C₃H₇, iso-C₃H₇, n-C₄H₉, iso-C₄H₉, iso-C₅H₁₁, n-C₅H₁₁, and n-C₆H₁₃] that have been synthesized and used in biochemical studies as inhibitors of serine hydrolases (Chekhlov et al., 1995; Makhaeva et al., 2005). These studies suggested the hypothesis that inhibition of serine hydrolases by FAP compounds occurs via scission of the P—C bond to organophosphorylate the active site serine (Makhaeva et al., 2005). Although P—C bonds are exceptionally stable in most phosphonates, enzymes such as bacterial carbon-phosphorus lyase are capable of catalyzing their cleavage, thus providing a potential method for destroying toxic phosphonates that might otherwise accumulate in the environment (Adams et al., 2008). Moreover, the structure of diisopentyl-FAP revealed a 1.888 (4) Å P—C bond (Chekhlov et al., 1995), which was calculated to be longer and weaker than P—C bonds in phosphonates lacking adjacent –CF₃ groups (Makhaeva et al., 2005).

To provide a further test of our hypothesis, the X-ray crystal structure of the title compound was determined (Fig 1). The title compound contains an intramolecular P=O···H—N hydrogen bond (Fig. 1; Table 1), and in the crystal it is linked via two intermolecular P=O···H—N hydrogen bonds to form inversion-related dimers (Fig. 2; Table 1). As predicted, the structure of diethyl-FAP revealed an elongated P—C bond that was 1.8797 (13) Å in length, which is not significantly different from the 1.888 (4) Å P—C bond in diisopentyl-FAP (Chekhlov et al., 1995). This is long compared to P—C bond lengths of 1.822 (2) Å (Chen et al., 2008), 1.803 (4) Å (Guo et al., 2008), 1.818 (5) Å (Kachkovskyi and Kolodiazhnyi, 2007), and 1.805 (6) Å (Liu et al., 1995) reported for the crystal structures of a variety of dialkyl phosphonates lacking α-CF₃ groups. The long P—C bond in diethyl-FAP is expected to be labile and would explain the ability of the compound to organophosphorylate and inhibit serine hydrolases as well as their ability to undergo hydrolysis to yield phosphoric acid diethyl ester and the amide, (CF₃)₂CH–NH–SO₂–C₆H₅(Makhaeva et al., 2005).

Experimental

The title compound was synthesized by mixing ether solutions of equimolar amounts of diethylphosphite and the sulfonylimine of hexafluoroacetone followed by subsequent recrystallization from petroleum ether.

Colorless plates of the ethyl analog were grown via evaporation from methanol at 22 °C. A crystal with dimensions of 0.60 × 0.42 × 0.40 mm was cut from a larger crystal and mounted on a standard Bruker SMART CCD-based X-ray diffractometer equipped with a LT-2 low temperature device and normal focus Mo-target X-ray tube (λ = 0.71073 Å) operated at 2000 W power (50 kV, 40 mA). X-ray intensities were measured at 113 (2) K with the detector placed 4.980 cm from the crystal. A total of 3030 frames were collected with a scan width of 0.3° in ω and φ and an exposure time of 20 sec/frame.

Data integration yielded a total of 20001 reflections to a maximum 2θ value of 56.58° of which 4568 were independent and 4343 were greater than 2 σ(I). The final cell constants were based on the xyz centroids of 6691 reflections above 10 σ(I).