3-Hydro­xy-6-methyl-2-[4-(3-tri­fluoromethyl­phenyl)­piperazin-1-yl­methyl]-4H-pyran-4-one

In the structure of the title compound, 3-hydroxy-6-methyl-2-[4-(3-tri­fluoro­methyl­phenyl)piperazin-1-yl­methyl]-4H-pyran-4-one, C₁₈H₁₉F₃N₂O₃, the piperazine ring displays an almost perfect chair conformation, with the substituents at the N atoms lying in equatorial positions. The conformation of the mol­ecule is determined by intra- and intermolecular hydrogen bonds.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.005 Å
• R factor = 0.050
• wR factor = 0.121
• Data-to-parameter ratio = 12.8

checkCIF/PLATON results

No syntax errors found



Alert level A
PLAT242_ALERT_2_A Check Low    U(eq) as Compared to Neighbors ....        C18

Alert level B
PLAT026_ALERT_3_B Ratio Observed / Unique Reflections too Low ....         38 Perc.
PLAT029_ALERT_3_B _diffrn_measured_fraction_theta_full Low .......       0.95

Alert level C
GOODF01_ALERT_2_C  The least squares goodness of fit parameter lies
            outside the range 0.80 <> 2.00
            Goodness of fit given =      0.699
REFLT03_ALERT_3_C  Reflection count < 95% complete
           From the CIF: _diffrn_reflns_theta_max           26.00
           From the CIF: _diffrn_reflns_theta_full           0.00
           From the CIF: _reflns_number_total               3265
           TEST2: Reflns within _diffrn_reflns_theta_max
           Count of symmetry unique reflns         3447
           Completeness (_total/calc)             94.72%
PLAT022_ALERT_3_C Ratio Unique / Expected Reflections too Low ....       0.95
PLAT063_ALERT_3_C Crystal Probably too Large for Beam Size .......       0.80 mm
PLAT301_ALERT_3_C Main Residue  Disorder .........................       7.00 Perc.
PLAT340_ALERT_3_C Low Bond Precision on C-C bonds (x 1000) Ang ...          5
PLAT410_ALERT_2_C Short Intra H...H Contact  H9B    ..  H13      =       1.98 Ang.
PLAT779_ALERT_2_C Suspect or Irrelevant (Bond) Angle in CIF ......      30.60 Deg.
              F3A  -C18  -F3B     1.555   1.555   1.555
PLAT779_ALERT_2_C Suspect or Irrelevant (Bond) Angle in CIF ......      26.20 Deg.
              F1B  -C18  -F1A     1.555   1.555   1.555

   1 ALERT level A = In general: serious problem
   2 ALERT level B = Potentially serious problem
   9 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
   5 ALERT type 2 Indicator that the structure model may be wrong or deficient
   7 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion

---

Computing details

Data collection: X-AREA (Stoe & Cie, 2002); cell refinement: X-AREA; data reduction: X-RED32 (Stoe & Cie, 2002); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Burnett & Johnson, 1996); software used to prepare material for publication: WinGX (Farrugia, 1997) and PARST (Nardelli, 1995).

3-Hydroxy-6-methyl-2-[4-(3-trifluoromethylphenyl)piperazin-1-ylmethyl]- 4H-pyran-4-one

Crystal data

C18H19F3N2O3	F(000) = 768
Mr = 368.36	Dx = 1.391 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 3360 reflections
a = 15.5021 (15) Å	θ = 1.9–23.2°
b = 10.5534 (16) Å	µ = 0.12 mm^−1
c = 11.2637 (11) Å	T = 293 K
β = 107.294 (8)°	Prism, colourless
V = 1759.4 (4) Å^3	0.80 × 0.32 × 0.06 mm
Z = 4

Data collection

Stoe IPDS 2 diffractometer	1246 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.093
Graphite monochromator	θmax = 26.0°, θmin = 2.4°
Detector resolution: 6.67 pixels mm^-1	h = −19→17
rotation method scans	k = −12→12
12432 measured reflections	l = −13→12
3265 independent reflections

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)] = 0.050	H-atom parameters constrained
wR(F^2) = 0.121	w = 1/[σ^2(Fo^2) + (0.0603P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 0.70	(Δ/σ)max = 0.001
3265 reflections	Δρmax = 0.25 e Å^−3
256 parameters	Δρmin = −0.18 e Å^−3
80 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0144 (13)

Special details

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	Occ. (<1)
F1A	−0.0917 (11)	0.4631 (9)	0.470 (2)	0.197 (7)	0.52 (2)
F1B	−0.1113 (11)	0.4435 (13)	0.4203 (14)	0.137 (4)	0.48 (2)
F2	−0.1658 (3)	0.4168 (3)	0.5712 (3)	0.1874 (15)
F3A	−0.2090 (8)	0.3183 (12)	0.433 (2)	0.183 (7)	0.52 (2)
F3B	−0.1853 (10)	0.3176 (14)	0.3902 (11)	0.140 (4)	0.48 (2)
O1	0.50485 (14)	0.22668 (17)	0.49483 (18)	0.0579 (6)
O2	0.37174 (15)	0.23843 (17)	0.17540 (18)	0.0630 (6)
H2	0.3759	0.2872	0.1207	0.094*
O3	0.47424 (17)	0.4549 (2)	0.1976 (2)	0.0772 (7)
N1	0.31830 (16)	0.12172 (19)	0.4600 (2)	0.0488 (6)
N2	0.14465 (18)	0.1282 (2)	0.5018 (2)	0.0621 (7)
C1	0.44188 (19)	0.1999 (2)	0.3840 (3)	0.0460 (7)
C2	0.5605 (2)	0.3269 (3)	0.5041 (3)	0.0630 (9)
C3	0.6231 (2)	0.3385 (3)	0.6312 (3)	0.0867 (11)
H3A	0.6122	0.2708	0.6819	0.130*
H3B	0.6135	0.4184	0.6662	0.130*
H3C	0.6843	0.3340	0.6283	0.130*
C4	0.5541 (2)	0.4031 (3)	0.4066 (3)	0.0662 (9)
H4	0.5941	0.4706	0.4160	0.079*
C5	0.4885 (2)	0.3842 (3)	0.2895 (3)	0.0570 (8)
C6	0.4330 (2)	0.2696 (3)	0.2832 (3)	0.0488 (7)
C7	0.3842 (2)	0.0891 (2)	0.3944 (3)	0.0536 (8)
H7A	0.3522	0.0588	0.3117	0.064*
H7B	0.4225	0.0210	0.4384	0.064*
C8	0.2451 (2)	0.1999 (3)	0.3824 (3)	0.0590 (8)
H8A	0.2127	0.1526	0.3088	0.071*
H8B	0.2704	0.2750	0.3557	0.071*
C9	0.1809 (2)	0.2384 (3)	0.4526 (3)	0.0639 (9)
H9A	0.2120	0.2934	0.5209	0.077*
H9B	0.1313	0.2859	0.3978	0.077*
C10	0.2771 (2)	0.0057 (3)	0.4911 (3)	0.0593 (8)
H10A	0.3241	−0.0506	0.5390	0.071*
H10B	0.2443	−0.0377	0.4152	0.071*
C11	0.2140 (2)	0.0369 (3)	0.5645 (3)	0.0641 (9)
H11A	0.1850	−0.0403	0.5796	0.077*
H11B	0.2485	0.0711	0.6444	0.077*
C12	0.0746 (3)	0.1499 (3)	0.5523 (3)	0.0623 (9)
C13	0.0107 (2)	0.2449 (3)	0.5057 (3)	0.0701 (9)
H13	0.0170	0.2970	0.4422	0.084*
C14	−0.0613 (3)	0.2634 (4)	0.5513 (3)	0.0756 (10)
C15	−0.0741 (3)	0.1880 (4)	0.6455 (4)	0.0880 (12)
H15	−0.1225	0.2011	0.6767	0.106*
C16	−0.0123 (3)	0.0931 (4)	0.6908 (4)	0.0897 (12)
H16	−0.0198	0.0404	0.7532	0.108*
C17	0.0607 (3)	0.0738 (3)	0.6461 (3)	0.0737 (10)
H17	0.1013	0.0088	0.6793	0.088*
C18	−0.1302 (3)	0.3597 (4)	0.4947 (5)	0.0975 (13)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
F1A	0.110 (7)	0.071 (5)	0.43 (2)	0.001 (4)	0.105 (11)	−0.016 (7)
F1B	0.109 (8)	0.173 (9)	0.169 (9)	0.058 (5)	0.101 (6)	0.069 (6)
F2	0.211 (4)	0.193 (3)	0.203 (3)	0.072 (3)	0.130 (3)	−0.022 (3)
F3A	0.078 (5)	0.107 (5)	0.340 (17)	0.002 (4)	0.023 (8)	−0.059 (8)
F3B	0.129 (8)	0.147 (7)	0.119 (7)	0.056 (5)	−0.002 (5)	−0.028 (4)
O1	0.0536 (13)	0.0594 (12)	0.0627 (13)	0.0003 (11)	0.0205 (11)	−0.0011 (10)
O2	0.0716 (16)	0.0544 (13)	0.0619 (13)	−0.0133 (11)	0.0182 (12)	0.0071 (10)
O3	0.0989 (19)	0.0640 (14)	0.0759 (15)	−0.0237 (12)	0.0371 (14)	0.0044 (12)
N1	0.0511 (16)	0.0432 (13)	0.0578 (15)	−0.0010 (11)	0.0250 (13)	0.0054 (11)
N2	0.0633 (18)	0.0614 (16)	0.0717 (17)	−0.0085 (14)	0.0356 (15)	0.0035 (13)
C1	0.0404 (18)	0.0485 (17)	0.0518 (17)	0.0074 (13)	0.0180 (15)	−0.0032 (14)
C2	0.055 (2)	0.071 (2)	0.067 (2)	−0.0082 (17)	0.0236 (18)	−0.0120 (18)
C3	0.076 (3)	0.099 (3)	0.076 (2)	−0.010 (2)	0.010 (2)	−0.017 (2)
C4	0.062 (2)	0.067 (2)	0.078 (2)	−0.0173 (17)	0.033 (2)	−0.0168 (18)
C5	0.059 (2)	0.0532 (18)	0.069 (2)	−0.0078 (16)	0.0340 (18)	−0.0108 (17)
C6	0.0464 (19)	0.0516 (17)	0.0503 (18)	−0.0019 (14)	0.0169 (16)	−0.0062 (15)
C7	0.0555 (19)	0.0476 (17)	0.062 (2)	0.0032 (14)	0.0239 (17)	0.0052 (14)
C8	0.052 (2)	0.0628 (19)	0.068 (2)	0.0006 (16)	0.0264 (17)	0.0103 (15)
C9	0.054 (2)	0.0621 (19)	0.083 (2)	0.0051 (16)	0.0324 (18)	0.0175 (17)
C10	0.069 (2)	0.0453 (17)	0.072 (2)	−0.0062 (15)	0.0334 (18)	0.0010 (15)
C11	0.076 (2)	0.0503 (18)	0.074 (2)	−0.0074 (17)	0.0346 (19)	0.0053 (16)
C12	0.066 (2)	0.067 (2)	0.064 (2)	−0.0195 (18)	0.0333 (19)	−0.0149 (17)
C13	0.064 (2)	0.071 (2)	0.089 (2)	−0.0105 (19)	0.043 (2)	−0.0158 (19)
C14	0.067 (3)	0.084 (3)	0.088 (3)	−0.022 (2)	0.041 (2)	−0.032 (2)
C15	0.067 (3)	0.119 (3)	0.091 (3)	−0.033 (3)	0.043 (2)	−0.042 (3)
C16	0.082 (3)	0.118 (3)	0.083 (3)	−0.035 (3)	0.045 (3)	−0.011 (2)
C17	0.073 (3)	0.083 (2)	0.073 (2)	−0.0212 (19)	0.034 (2)	−0.0056 (19)
C18	0.082 (3)	0.101 (3)	0.131 (4)	−0.006 (3)	0.064 (3)	−0.033 (3)

Geometric parameters (Å, º)

F1A—C18	1.311 (9)	C4—H4	0.9300
F1B—C18	1.310 (8)	C5—C6	1.474 (4)
F1B—F3B	1.72 (2)	C7—H7A	0.9700
F2—C18	1.301 (5)	C7—H7B	0.9700
F3A—C18	1.289 (9)	C8—C9	1.500 (4)
F3B—C18	1.309 (9)	C8—H8A	0.9700
O1—C2	1.349 (4)	C8—H8B	0.9700
O1—C1	1.366 (3)	C9—H9A	0.9700
O2—C6	1.341 (3)	C9—H9B	0.9700
O2—H2	0.8200	C10—C11	1.493 (4)
O3—C5	1.241 (3)	C10—H10A	0.9700
N1—C8	1.463 (3)	C10—H10B	0.9700
N1—C7	1.469 (3)	C11—H11A	0.9700
N1—C10	1.470 (3)	C11—H11B	0.9700
N2—C12	1.387 (4)	C12—C17	1.394 (4)
N2—C11	1.460 (4)	C12—C13	1.398 (4)
N2—C9	1.470 (3)	C13—C14	1.374 (5)
C1—C6	1.325 (4)	C13—H13	0.9300
C1—C7	1.498 (4)	C14—C15	1.387 (5)
C2—C4	1.340 (4)	C14—C18	1.475 (6)
C2—C3	1.477 (4)	C15—C16	1.375 (5)
C3—H3A	0.9600	C15—H15	0.9300
C3—H3B	0.9600	C16—C17	1.384 (5)
C3—H3C	0.9600	C16—H16	0.9300
C4—C5	1.421 (4)	C17—H17	0.9300
C18—F1B—F3B	48.9 (7)	C8—C9—H9B	109.2
C18—F3B—F1B	48.9 (7)	H9A—C9—H9B	107.9
C2—O1—C1	120.0 (2)	N1—C10—C11	110.5 (2)
C6—O2—H2	109.5	N1—C10—H10A	109.5
C8—N1—C7	111.2 (2)	C11—C10—H10A	109.5
C8—N1—C10	107.3 (2)	N1—C10—H10B	109.5
C7—N1—C10	109.9 (2)	C11—C10—H10B	109.5
C12—N2—C11	117.7 (3)	H10A—C10—H10B	108.1
C12—N2—C9	117.3 (3)	N2—C11—C10	112.8 (3)
C11—N2—C9	113.3 (3)	N2—C11—H11A	109.0
C6—C1—O1	122.2 (3)	C10—C11—H11A	109.0
C6—C1—C7	126.0 (3)	N2—C11—H11B	109.0
O1—C1—C7	111.8 (2)	C10—C11—H11B	109.0
C4—C2—O1	121.1 (3)	H11A—C11—H11B	107.8
C4—C2—C3	127.7 (3)	N2—C12—C17	122.1 (3)
O1—C2—C3	111.2 (3)	N2—C12—C13	121.2 (3)
C2—C3—H3A	109.5	C17—C12—C13	116.5 (4)
C2—C3—H3B	109.5	C14—C13—C12	121.7 (4)
H3A—C3—H3B	109.5	C14—C13—H13	119.2
C2—C3—H3C	109.5	C12—C13—H13	119.2
H3A—C3—H3C	109.5	C13—C14—C15	121.4 (4)
H3B—C3—H3C	109.5	C13—C14—C18	120.1 (4)
C2—C4—C5	122.3 (3)	C15—C14—C18	118.5 (4)
C2—C4—H4	118.8	C16—C15—C14	117.4 (4)
C5—C4—H4	118.8	C16—C15—H15	121.3
O3—C5—C4	126.2 (3)	C14—C15—H15	121.3
O3—C5—C6	119.8 (3)	C15—C16—C17	121.8 (4)
C4—C5—C6	113.9 (3)	C15—C16—H16	119.1
C1—C6—O2	120.4 (3)	C17—C16—H16	119.1
C1—C6—C5	120.3 (3)	C16—C17—C12	121.2 (4)
O2—C6—C5	119.4 (3)	C16—C17—H17	119.4
N1—C7—C1	112.1 (2)	C12—C17—H17	119.4
N1—C7—H7A	109.2	F3A—C18—F2	89.6 (11)
C1—C7—H7A	109.2	F3A—C18—F3B	30.6 (12)
N1—C7—H7B	109.2	F2—C18—F3B	117.4 (8)
C1—C7—H7B	109.2	F3A—C18—F1B	103.9 (15)
H7A—C7—H7B	107.9	F2—C18—F1B	109.3 (7)
N1—C8—C9	110.8 (2)	F3B—C18—F1B	82.2 (13)
N1—C8—H8A	109.5	F3A—C18—F1A	125.9 (16)
C9—C8—H8A	109.5	F2—C18—F1A	93.5 (8)
N1—C8—H8B	109.5	F3B—C18—F1A	108.1 (14)
C9—C8—H8B	109.5	F1B—C18—F1A	26.2 (11)
H8A—C8—H8B	108.1	F3A—C18—C14	116.6 (7)
N2—C9—C8	111.9 (3)	F2—C18—C14	115.3 (4)
N2—C9—H9A	109.2	F3B—C18—C14	110.5 (7)
C8—C9—H9A	109.2	F1B—C18—C14	118.0 (7)
N2—C9—H9B	109.2	F1A—C18—C14	110.3 (8)
C2—O1—C1—C6	0.1 (4)	C9—N2—C12—C17	−151.4 (3)
C2—O1—C1—C7	−177.4 (3)	C11—N2—C12—C13	173.4 (3)
C1—O1—C2—C4	1.3 (5)	C9—N2—C12—C13	32.8 (4)
C1—O1—C2—C3	−179.9 (3)	N2—C12—C13—C14	177.0 (3)
O1—C2—C4—C5	0.8 (5)	C17—C12—C13—C14	0.9 (4)
C3—C2—C4—C5	−177.7 (3)	C12—C13—C14—C15	−0.3 (5)
C2—C4—C5—O3	174.8 (3)	C12—C13—C14—C18	−176.4 (3)
C2—C4—C5—C6	−3.9 (4)	C13—C14—C15—C16	−0.6 (5)
O1—C1—C6—O2	178.4 (2)	C18—C14—C15—C16	175.5 (3)
C7—C1—C6—O2	−4.5 (5)	C14—C15—C16—C17	0.9 (5)
O1—C1—C6—C5	−3.4 (4)	C15—C16—C17—C12	−0.3 (5)
C7—C1—C6—C5	173.6 (3)	N2—C12—C17—C16	−176.6 (3)
O3—C5—C6—C1	−173.7 (3)	C13—C12—C17—C16	−0.6 (4)
C4—C5—C6—C1	5.1 (4)	F1B—F3B—C18—F3A	135 (2)
O3—C5—C6—O2	4.5 (4)	F1B—F3B—C18—F2	107.8 (9)
C4—C5—C6—O2	−176.7 (3)	F1B—F3B—C18—F1A	3.7 (12)
C8—N1—C7—C1	73.3 (3)	F1B—F3B—C18—C14	−117.1 (8)
C10—N1—C7—C1	−168.0 (2)	F3B—F1B—C18—F3A	−21.8 (11)
C6—C1—C7—N1	−103.1 (3)	F3B—F1B—C18—F2	−116.4 (8)
O1—C1—C7—N1	74.2 (3)	F3B—F1B—C18—F1A	−172 (3)
C7—N1—C8—C9	−177.0 (2)	F3B—F1B—C18—C14	109.1 (9)
C10—N1—C8—C9	62.7 (3)	C13—C14—C18—F3A	110.5 (14)
C12—N2—C9—C8	−170.6 (3)	C15—C14—C18—F3A	−65.7 (14)
C11—N2—C9—C8	47.1 (3)	C13—C14—C18—F2	−146.3 (4)
N1—C8—C9—N2	−55.7 (3)	C15—C14—C18—F2	37.6 (6)
C8—N1—C10—C11	−62.3 (3)	C13—C14—C18—F3B	77.6 (10)
C7—N1—C10—C11	176.6 (2)	C15—C14—C18—F3B	−98.6 (10)
C12—N2—C11—C10	170.6 (2)	C13—C14—C18—F1B	−14.4 (11)
C9—N2—C11—C10	−47.3 (3)	C15—C14—C18—F1B	169.4 (10)
N1—C10—C11—N2	55.4 (3)	C13—C14—C18—F1A	−41.9 (11)
C11—N2—C12—C17	−10.8 (4)	C15—C14—C18—F1A	141.9 (10)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C9—H9A···O2^i	0.97	2.59	3.270 (4)	127
O2—H2···N1^ii	0.82	2.01	2.748 (3)	150
O2—H2···O3	0.82	2.33	2.752 (3)	113
C7—H7A···O2	0.97	2.51	2.885 (3)	103

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