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

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.

The title compound, C 13 H 16 F 6 NO 5 PS, 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-HÁ Á ÁO P hydrogen bonds, resulting in centrosymmetric dimers. An intramolecular N-HÁ Á ÁO P hydrogen bond is also present.

Comment
The title compound is a member of the fluorinated α-aminophosphonate (FAP) group of compounds [(RO) 2 P(O)C(CF 3 ) 2 NHS(O) 2 C 6 H 5 ; R = CH 3 , C 2 H 5 , C 3 H 7 , iso-C 3 H 7 , n-C 4 H 9 , iso-C 4 H 9 , iso-C 5 H 11 , n-C 5 H 11 , and n-C 6 H 13 ] 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 -CF 3 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) (Liu et al., 1995) reported for the crystal structures of a variety of dialkyl phosphonates lacking α-CF 3 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, (CF 3 ) 2 CH-NH-SO 2 -C 6 H 5 (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).

Refinement
The hydrogen atoms were treated as riding, with N-H distance = 0.88 Å and C-H distances in the range 0.95-0.99 Å with U iso (H) = 1.2U eq (N,C), 1.5U eq (C methyl ).  Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating Rfactors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.