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.

Key indicators

• Single-crystal X-ray study
• T = 113 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.029
• wR factor = 0.083
• Data-to-parameter ratio = 18.6

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT220_ALERT_2_C Large Non-Solvent    C     Ueq(max)/Ueq(min) ...       3.10 Ratio
PLAT222_ALERT_3_C Large Non-Solvent    H     Ueq(max)/Ueq(min) ...       3.97 Ratio
PLAT318_ALERT_2_C Check Hybridisation of  N1     in Main Residue .          ?
PLAT430_ALERT_2_C Short Inter D...A Contact  O3     ..  O3      ..       2.87 Ang.

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   4 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   3 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check


checkCIF publication errors

Alert level A
PUBL024_ALERT_1_A The number of authors is greater than 5.
              Please specify the role of each of the co-authors
              for your paper.

Author Response: All authors made significant scientific contributions to the work reported and share responsibility and accountability for the results. The co-editor has accepted all authors. The role(s) played by each co-author are as follows:

 Sanjeeva J. Wijeyesakere: Assisted with overall coordination of the project,
 literature research, writing the final draft of the paper, and preparation of
 the CIF.

 Faik A. Nasser: Developed the crystallization conditions, grew the crystals,
 helped with crystal selection, and wrote the first draft of the paper.

 Jeff W. Kampf: Crystal selection, cutting, and mounting; experimental data
 collection; data reduction; structure solution and refinement; and graphical
 representations.

 Vladimir B. Sokolov: Development of synthesis technique; synthesis and analysis
 of chemical reactivity.

 Alexey Y. Aksinenko: Synthesis and analysis of chemical reactivity.

 Vladimir V. Malygin: Analysis of data on serine esterase inhibition; hypothesis
 about P-C bond scission.

 Galina F. Makhaeva: Biochemical studies of FAP as inhibitors of serine
 hydrolases; hypotheses about P-C bond scission and dimerization of FAP
 molecules; Director of Russian group; secured funding for Russian group.

 Rudy J. Richardson: Corresponding author; preparation of figures; check of
 final draft; Director of US group; secured funding for US group; overall
 coordination of project for the Russian and US groups.


   1 ALERT level A = Data missing that is essential or data in wrong format
   0 ALERT level G = General alerts. Data that may be required is missing

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S1. 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).

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).

S2. 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).

S3. 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).

Computing details

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

Figures

	Fig. 1. Structure of diethyl-FAP showing the atom numbering scheme. The intramolecular hydrogen bond is shown as a dashed line. Ellipsoids represent 50% occupancy.
	Fig. 2. The dimer of diethyl-FAP, showing the intermolecular hydrogen bonds and the atom labelling scheme.

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

Crystal data

C13H16F6NO5PS	F(000) = 904
Mr = 443.3	Dx = 1.596 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 6567 reflections
a = 11.6913 (15) Å	θ = 2.9–28.3°
b = 10.1375 (13) Å	µ = 0.35 mm^−1
c = 15.5955 (19) Å	T = 113 K
β = 93.264 (2)°	Plate, colourless
V = 1845.4 (4) Å^3	0.60 × 0.42 × 0.40 mm
Z = 4

Data collection

Bruker SMART CCD area-detector diffractometer	4568 independent reflections
Radiation source: fine-focus sealed tube	4027 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.022
ϕ and ω scans	θmax = 28.3°, θmin = 2.9°
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	h = −15→15
Tmin = 0.820, Tmax = 0.874	k = −13→13
20001 measured reflections	l = −20→20

Refinement

Refinement on F^2	0 restraints
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.029	w = 1/[σ^2(Fo^2) + (0.0427P)^2 + 0.6948P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.082	(Δ/σ)max = 0.001
S = 1.03	Δρmax = 0.34 e Å^−3
4568 reflections	Δρmin = −0.33 e Å^−3
246 parameters

Special details

Experimental. 2103 frames × 20 sec @ 4.980 cm; 0.3 ° scans in ω & ϕ

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	0.64284 (3)	0.17485 (3)	0.04487 (2)	0.02726 (9)
S1	0.33796 (3)	0.15018 (3)	0.174771 (18)	0.02622 (8)
N1	0.46059 (9)	0.12554 (10)	0.13045 (6)	0.0247 (2)
H1A	0.4569	0.0699	0.0870	0.030*
F1	0.73735 (8)	0.14398 (10)	0.24829 (6)	0.0445 (2)
F2	0.66649 (8)	−0.02537 (9)	0.17986 (5)	0.0429 (2)
F3	0.57711 (8)	0.05961 (9)	0.28299 (5)	0.0412 (2)
F4	0.56725 (9)	0.33003 (9)	0.27115 (5)	0.0434 (2)
F5	0.67125 (8)	0.38612 (9)	0.16867 (6)	0.0415 (2)
F6	0.48768 (7)	0.39288 (8)	0.14967 (5)	0.03547 (19)
C1	0.26341 (11)	0.26504 (13)	0.10763 (7)	0.0255 (2)
C2	0.24216 (12)	0.23293 (14)	0.02114 (8)	0.0307 (3)
H2A	0.2676	0.1513	−0.0009	0.037*
C3	0.18337 (14)	0.32241 (16)	−0.03191 (9)	0.0398 (3)
H3A	0.1682	0.3022	−0.0909	0.048*
C4	0.14648 (15)	0.44131 (17)	0.00055 (9)	0.0435 (4)
H4A	0.1074	0.5028	−0.0366	0.052*
C5	0.16614 (14)	0.47135 (16)	0.08707 (9)	0.0402 (3)
H5A	0.1391	0.5522	0.1091	0.048*
C6	0.22553 (12)	0.38277 (14)	0.14136 (8)	0.0313 (3)
H6A	0.2399	0.4026	0.2005	0.038*
C7	0.57400 (11)	0.18007 (12)	0.15084 (8)	0.0258 (2)
C8	0.57452 (12)	0.32405 (14)	0.18606 (9)	0.0326 (3)
C9	0.63978 (13)	0.08914 (14)	0.21698 (9)	0.0342 (3)
C10	0.86488 (14)	0.16185 (18)	0.02046 (12)	0.0464 (4)
H10A	0.8876	0.2351	−0.0170	0.056*
H10B	0.8423	0.0853	−0.0161	0.056*
C11	0.96179 (17)	0.1256 (3)	0.08278 (18)	0.0793 (7)
H11A	0.9820	0.2017	0.1194	0.119*
H11B	1.0283	0.0995	0.0512	0.119*
H11C	0.9386	0.0519	0.1186	0.119*
C12	0.50917 (13)	0.29279 (16)	−0.07438 (9)	0.0367 (3)
H12A	0.4590	0.3713	−0.0728	0.044*
H12B	0.4613	0.2134	−0.0674	0.044*
C13	0.56368 (16)	0.28690 (17)	−0.15912 (10)	0.0455 (4)
H13A	0.6155	0.3622	−0.1640	0.068*
H13B	0.5040	0.2901	−0.2058	0.068*
H13C	0.6071	0.2046	−0.1628	0.068*
O1	0.27788 (9)	0.02744 (10)	0.16554 (6)	0.0339 (2)
O2	0.36007 (9)	0.20787 (10)	0.25771 (5)	0.0346 (2)
O3	0.61539 (8)	0.04887 (9)	0.00278 (6)	0.0311 (2)
O4	0.77052 (9)	0.20205 (12)	0.07141 (7)	0.0435 (3)
O5	0.59785 (9)	0.29985 (10)	−0.00394 (6)	0.0348 (2)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
P1	0.02908 (17)	0.02691 (17)	0.02539 (16)	0.00270 (12)	−0.00198 (12)	−0.00504 (12)
S1	0.03576 (17)	0.02732 (16)	0.01571 (13)	0.00577 (12)	0.00261 (11)	0.00207 (10)
N1	0.0305 (5)	0.0241 (5)	0.0192 (4)	0.0051 (4)	−0.0018 (4)	−0.0048 (4)
F1	0.0422 (5)	0.0527 (5)	0.0364 (4)	0.0091 (4)	−0.0185 (4)	−0.0058 (4)
F2	0.0575 (5)	0.0330 (4)	0.0363 (4)	0.0205 (4)	−0.0127 (4)	−0.0031 (3)
F3	0.0557 (5)	0.0430 (5)	0.0236 (4)	0.0084 (4)	−0.0093 (4)	0.0041 (3)
F4	0.0591 (6)	0.0422 (5)	0.0277 (4)	0.0078 (4)	−0.0074 (4)	−0.0163 (3)
F5	0.0415 (5)	0.0342 (5)	0.0479 (5)	−0.0042 (4)	−0.0065 (4)	−0.0146 (4)
F6	0.0423 (4)	0.0229 (4)	0.0404 (4)	0.0082 (3)	−0.0050 (3)	−0.0057 (3)
C1	0.0292 (6)	0.0292 (6)	0.0181 (5)	0.0059 (5)	0.0025 (4)	0.0009 (4)
C2	0.0388 (7)	0.0329 (7)	0.0202 (5)	0.0110 (5)	0.0005 (5)	−0.0027 (5)
C3	0.0523 (9)	0.0449 (8)	0.0215 (6)	0.0175 (7)	−0.0052 (6)	−0.0026 (5)
C4	0.0550 (9)	0.0439 (8)	0.0304 (7)	0.0243 (7)	−0.0075 (6)	0.0003 (6)
C5	0.0500 (8)	0.0379 (8)	0.0320 (7)	0.0214 (7)	−0.0022 (6)	−0.0062 (6)
C6	0.0371 (7)	0.0346 (7)	0.0222 (5)	0.0100 (5)	0.0012 (5)	−0.0042 (5)
C7	0.0319 (6)	0.0237 (6)	0.0210 (5)	0.0065 (5)	−0.0062 (4)	−0.0044 (4)
C8	0.0386 (7)	0.0287 (6)	0.0294 (6)	0.0053 (5)	−0.0067 (5)	−0.0091 (5)
C9	0.0412 (7)	0.0339 (7)	0.0261 (6)	0.0100 (6)	−0.0105 (5)	−0.0032 (5)
C10	0.0367 (8)	0.0492 (9)	0.0545 (10)	−0.0068 (7)	0.0128 (7)	−0.0050 (7)
C11	0.0352 (9)	0.110 (2)	0.0913 (17)	0.0118 (11)	−0.0041 (10)	−0.0132 (15)
C12	0.0365 (7)	0.0387 (8)	0.0345 (7)	0.0026 (6)	−0.0009 (5)	0.0107 (6)
C13	0.0660 (11)	0.0390 (8)	0.0318 (7)	0.0067 (7)	0.0048 (7)	0.0056 (6)
O1	0.0433 (5)	0.0309 (5)	0.0280 (4)	−0.0005 (4)	0.0077 (4)	0.0054 (4)
O2	0.0497 (6)	0.0391 (5)	0.0150 (4)	0.0111 (4)	0.0014 (4)	−0.0011 (4)
O3	0.0386 (5)	0.0286 (5)	0.0259 (4)	0.0044 (4)	0.0006 (4)	−0.0070 (4)
O4	0.0289 (5)	0.0543 (7)	0.0466 (6)	0.0028 (5)	−0.0028 (4)	−0.0166 (5)
O5	0.0443 (6)	0.0288 (5)	0.0308 (5)	−0.0027 (4)	−0.0012 (4)	0.0026 (4)

Geometric parameters (Å, º)

P1—O3	1.4632 (10)	C4—C5	1.390 (2)
P1—O4	1.5509 (11)	C4—H4A	0.9500
P1—O5	1.5545 (10)	C5—C6	1.3923 (19)
P1—C7	1.8797 (13)	C5—H5A	0.9500
S1—O2	1.4296 (9)	C6—H6A	0.9500
S1—O1	1.4321 (11)	C7—C9	1.5539 (17)
S1—N1	1.6458 (11)	C7—C8	1.5594 (17)
S1—C1	1.7629 (12)	C10—O4	1.4540 (19)
N1—C7	1.4549 (16)	C10—C11	1.496 (3)
N1—H1A	0.8800	C10—H10A	0.9900
F1—C9	1.3361 (17)	C10—H10B	0.9900
F2—C9	1.3419 (16)	C11—H11A	0.9800
F3—C9	1.3313 (18)	C11—H11B	0.9800
F4—C8	1.3359 (16)	C11—H11C	0.9800
F5—C8	1.3354 (18)	C12—O5	1.4687 (17)
F6—C8	1.3320 (16)	C12—C13	1.501 (2)
C1—C6	1.3870 (18)	C12—H12A	0.9900
C1—C2	1.3960 (16)	C12—H12B	0.9900
C2—C3	1.3838 (18)	C13—H13A	0.9800
C2—H2A	0.9500	C13—H13B	0.9800
C3—C4	1.386 (2)	C13—H13C	0.9800
C3—H3A	0.9500
O3—P1—O4	117.26 (6)	F6—C8—F5	107.48 (12)
O3—P1—O5	115.62 (6)	F6—C8—F4	108.02 (11)
O4—P1—O5	106.23 (6)	F5—C8—F4	106.43 (11)
O3—P1—C7	108.97 (6)	F6—C8—C7	110.65 (10)
O4—P1—C7	102.36 (6)	F5—C8—C7	110.84 (11)
O5—P1—C7	104.94 (6)	F4—C8—C7	113.15 (11)
O2—S1—O1	120.58 (6)	F3—C9—F1	107.88 (11)
O2—S1—N1	108.97 (6)	F3—C9—F2	106.91 (12)
O1—S1—N1	105.06 (6)	F1—C9—F2	107.63 (12)
O2—S1—C1	108.97 (6)	F3—C9—C7	111.92 (11)
O1—S1—C1	106.92 (6)	F1—C9—C7	112.07 (12)
N1—S1—C1	105.30 (5)	F2—C9—C7	110.20 (10)
C7—N1—S1	130.95 (8)	O4—C10—C11	106.50 (16)
C7—N1—H1A	114.5	O4—C10—H10A	110.4
S1—N1—H1A	114.5	C11—C10—H10A	110.4
C6—C1—C2	121.60 (11)	O4—C10—H10B	110.4
C6—C1—S1	120.05 (9)	C11—C10—H10B	110.4
C2—C1—S1	118.34 (10)	H10A—C10—H10B	108.6
C3—C2—C1	118.67 (12)	C10—C11—H11A	109.5
C3—C2—H2A	120.7	C10—C11—H11B	109.5
C1—C2—H2A	120.7	H11A—C11—H11B	109.5
C2—C3—C4	120.41 (13)	C10—C11—H11C	109.5
C2—C3—H3A	119.8	H11A—C11—H11C	109.5
C4—C3—H3A	119.8	H11B—C11—H11C	109.5
C3—C4—C5	120.51 (13)	O5—C12—C13	110.09 (13)
C3—C4—H4A	119.7	O5—C12—H12A	109.6
C5—C4—H4A	119.7	C13—C12—H12A	109.6
C4—C5—C6	119.89 (13)	O5—C12—H12B	109.6
C4—C5—H5A	120.1	C13—C12—H12B	109.6
C6—C5—H5A	120.1	H12A—C12—H12B	108.2
C1—C6—C5	118.90 (12)	C12—C13—H13A	109.5
C1—C6—H6A	120.5	C12—C13—H13B	109.5
C5—C6—H6A	120.5	H13A—C13—H13B	109.5
N1—C7—C9	109.28 (11)	C12—C13—H13C	109.5
N1—C7—C8	114.70 (10)	H13A—C13—H13C	109.5
C9—C7—C8	109.24 (10)	H13B—C13—H13C	109.5
N1—C7—P1	103.16 (8)	C10—O4—P1	123.57 (10)
C9—C7—P1	110.27 (9)	C12—O5—P1	122.10 (9)
C8—C7—P1	110.04 (9)

Hydrogen-bond geometry (Å, º)

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···O3^i	0.88	2.00	2.8324 (14)	158

Symmetry code: (i) −x+1, −y, −z.