research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 71| Part 2| February 2015| Pages 199-202
doi:10.1107/S2056989015000936

Crystal structures of N-tert-butyl-3-(4-fluoro­phenyl)-5-oxo-4-[2-(tri­fluoro­meth­­oxy)phen­yl]-2,5-di­hydro­furan-2-carboxamide and 4-(2H-1,3-benzodioxol-5-yl)-N-cyclo­hexyl-5-oxo-3-[4-(tri­fluoro­meth­yl)phen­yl]-2,5-di­hydro­furan-2-carboxamide

Sue A. Roberts,a* Guillermo Martinez-Arizab and Christopher Hulmeb

aChemistry and Biochemistry, University of Arizona, 1306 E. University Blvd, Tucson, AZ 85721, USA, and bDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA
*Correspondence e-mail: suer@email.arizona.edu

Edited by A. J. Lough, University of Toronto, Canada (Received 15 December 2014; accepted 15 January 2015; online 24 January 2015)

The title compounds, C22H19F4NO4, (I), and C25H22F3NO5, (II), each contain a central nearly planar di­hydro­furan­one ring. The r.m.s. deviation from planarity of these rings is 0.015 Å in (I) and 0.027 Å in (II). The mol­ecules are T-shaped, with the major conformational difference being the O—C—C—O torsion angle [−178.9 (1) in (I) and 37.7 (2)° in (II)]. In the crystal of (I), mol­ecules are linked by N—H⋯O hydrogen bonds, forming chains along [001] while in (II) mol­ecules are linked by N—H⋯O hydrogen bonds, forming chains along [010]. In (II), the tri­fluoro­methyl substituent is disordered over two sets of sites, with refined occupancies of 0.751 (3) and 0.249 (3).

CCDC references: 1043839; 1043838

1. Chemical context

Butenolides, also known as furan-2(5H)-ones or furan­ones, are a recurrent moiety in more than 13,000 natural products (De Souza, 2005[De Souza, M. V. N. (2005). Mini-Rev. Org. Chem. 2, 139-145.]) and possess different assorted biological applications, exemplified by cytotoxic (Jung et al., 1990[Jung, J. H., Pummangura, S., Chaichantipyuth, C., Patarapanich, C., Fanwick, P. E., Chang, C.-J. & Mclaughlin, J. L. (1990). Tetrahedron, 46, 5043-5054.]) and anti­biotic (Sikorska et al., 2012[Sikorska, J., Parker-Nance, S., Davies-Coleman, M., Vining, O. B., Sikora, A. E. & McPhail, K. L. J. (2012). J. Nat. Prod. 75, 1824-1827]) activities. Likewise, the butenolide derivative Vioxx® is a potent NSAID (non-steroidal anti-inflammatory drug) used for the relief of pain and inflammation (Prasit et al., 1999[Prasit, P., et al. (1999). Bioorg. Med. Chem. Lett. 9, 1773-1778.]) before it was withdrawn from the market in 2004. As a part of our scientific endeavors to access and mimic the complexity and diversity present in naturally occurring mol­ecular scaffolds, the title compounds were synthesized using a Passerini/Knoevenagel sequence and the crystal structures are reported herein. Other multi-component reaction-based approaches towards furan­ones have been reported, but they use limited starting materials. For example, they use unstable phospho­nates (Beck et al., 2001[Beck, B., Magnin-Lachaux, M., Herdtweck, E. & Dömling, A. (2001). Org. Lett. 3, 2875-2878.]), aliphatic substituents (Bossio et al., 1993[Bossio, R., Marcaccini, S., Pepino, R. & Torroba, T. (1993). Synthesis, pp. 783-785.], 1994[Bossio, R., Marcaccini, S. & Pepino, R. (1994). Liebigs Ann. Chem. 1994, 527-528.]; Marcaccini et al., 2000[Marcaccini, S., Pepino, R., Marcos, C. F., Polo, C. & Torroba, T. (2000). J. Heterocycl. Chem. 37, 1501-1503.]), or tricarbonyl inputs (Rossbach et al., 2014[Rossbach, J., Harms, K. & Koert, U. (2014). Eur. J. Org. Chem. pp. 993-1006.]).

2. Structural commentary

The mol­ecular structures of N-tert-butyl-3-(4-fluoro­phen­yl)-5-oxo-4-[2-(tri­fluoro­meth­oxy)phen­yl]-2,5-di­hydrofuran-2-carboxamide (I)[link] (Fig. 1[link]) and 4-(2H-1,3-benzodioxol-5-yl)-N-cyclo­hexyl-5-oxo-3-[4-(tri­fluoro­meth­yl)phen­yl]-2,5-di­hydrofuran-2-carboxamide (II)[link] (Fig. 2[link]) are similar. The mol­ecules are T-shaped, with the major conformational difference being the O1—C—C—O2 torsion angle. In (I)[link], this torsion angle is −178.9 (1)°, whereas in (II)[link], it is 37.7 (2)°.

[Scheme 1]
[Scheme 2]
[Figure 1]
Figure 1
The mol­ecular structure of (I)[link]. Anisotropically refined atoms are shown as 50% probability displacement ellipsoids.
[Figure 2]
Figure 2
The mol­ecular structure of (II)[link]. The –CF3 substituent is disordered and only the major component is shown. Anisotropically refined atoms are shown as 50% probability displacement ellipsoids.

In (II)[link], the amide oxygen atom, O1, is tucked between O2 and H1A, with contact distances to O2 of 2.738 (1) Å and to H1A of 2.54 Å. The central, di­hydro­furan­one ring is nearly planar in both compounds. The r.m.s. deviation of these central rings is 0.015 Å in (I)[link], and 0.027 Å in (II)[link]. In (I)[link], the dihedral angle between the furan ring and the p-fluoro substituted benzene ring is 44.66 (4)° and with the tri­fluoro­meth­oxy-substituted benzene ring it is 48.71 (3)°. In (II)[link], the dihedral angle between the furan ring and the p-tri­fluoro­methyl substituted benzene ring is 40.03 (5)° and the dihedral angle with the benzene ring of the benzo[1,3]dioxol-5-yl ring system is 43.06 (6)°. The cyclo­hexane ring of (II)[link] is in a chair conformation.

The –CF3 substituent of (II)[link] is disordered over two sets of sites. In the major component [occupancy = 0.751 (3)], F2A has a close contact to atom O1 [2.772 (2) Å] of a neighbouring molecule, which is lengthened to 3.093 (6) Å in the alternate configuration i.e. the minor component. Two hydrogen atoms from symmetry-equivalent mol­ecules flank F3B (H2A, 2.72 Å, and H23, 2.57 Å) and prevent rotational disorder from alleviating the close contact. In the minor component, the –CF3 group deviates from the plane of the aromatic ring, with C25B displaced by 0.36 (1) Å from the mean plane of the aromatic ring.

3. Supra­molecular features

In both crystals, N—H⋯O hydrogen bonds connect the mol­ecules into chains which run, in (I)[link] along the c-axis direction (Table 1[link]), and in (II)[link] along the b-axis direction (Table 2[link]). The hydrogen-bonding graph set is C(4) in both (I)[link] and (II)[link]. The partial packing plots of (I)[link] (Fig. 3[link]) and (II)[link] (Fig. 4[link]) illustrate the hydrogen-bonding motifs.

Table 1
Hydrogen-bond geometry (Å, °) for (I)[link]

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N1—H1⋯O1i 0.845 (17) 2.209 (17) 3.0098 (14) 158.2 (15)
Symmetry code: (i) [x, -y+{\script{1\over 2}}, z-{\script{1\over 2}}].

Table 2
Hydrogen-bond geometry (Å, °) for (II)[link]

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N1—H1⋯O1i 0.821 (18) 2.061 (18) 2.8699 (16) 168.4 (16)
Symmetry code: (i) [-x+{\script{3\over 2}}, y-{\script{1\over 2}}, z].
[Figure 3]
Figure 3
Part of the crystal structure of (I)[link] viewed along [100]. The hydrogen bonds linking the mol­ecules into chains along [001] are shown as dotted lines.
[Figure 4]
Figure 4
A hydrogen-bonded chain of mol­ecules of (II)[link] propagating along [010]. The view is along the [100] direction. Hydrogen bonds are shown as dotted lines.

4. Database survey

The Cambridge Structural Database (CSD) contains few examples of 3,4,5-substituted furan-2(5H)-ones. A search (CSD Version 5.36, November 2014; Groom & Allen, 2014[Groom, C. R. & Allen, F. H. (2014). Angew. Chem. Int. Ed. 53, 662-671.]) found only one other structure with an amide attachment at the position 5 carbon, TIFXIP (Beck et. al, 2001). For TIFXIP, the O1—C—C—O2 torsion angles for the two mol­ecules in the asymmetric unit are −40.1 and 40.4°, similar to that found in (II)[link], and the O1⋯O2 distances are 2.76 and 2.78 Å. When the search is expanded to include mol­ecules with a second organic substituent on the furan 5-carbon, additional structures are found. In six structures, where only one of the substituents is an amide, the O1—C—C—O2 torsion angle is 180° ± 30° (−150 to 150°); the value of −178.8 (1)° found for (I)[link] falls in this range.

5. Synthesis and crystallization

Compound (I): 4-fluoro­phenyl­glyoxal (1 eq., 0.5 mmol), tri­fluoro­meth­oxyphenyl­acetic acid (1 eq., 0.5 mmol) and tert-butyl isocyanide (1eq., 0.5 mmol) were dissolved in DCM (2 mL) and stirred at room temperature for 1 h. After confirming the exclusive formation of the Passerini product (via TLC and LC/MS), the solvent was removed and the crude product was dissolved in DMF (2 mL). Diiso­propyl­amine (DIPEA) (2 eq., 1 mmol, 140 µL) was added and the reaction mixture was heated at 393 K using microwave irradiation for 20 minutes. After cooling and verifying reaction completion (TLC and LC/MS), the crude mixture was directly purified by flash chromatography (EtOAc/hexane 0–100%) using an ISCO TM flash chromatography system to afford N-tert-butyl-3-(4-fluoro­phen­yl)-5-oxo-4-[2-(tri­fluoro­meth­oxy)phen­yl]-2,5-di­hydro­furan-2-carboxamide as a beige solid (67% yield).

Compound (II): 4-tri­fluoro­methyl­phenyl­glyoxal (1 eq., 0.5 mmol), 3,4-methyl­ene­dioxy­phenyl­acetic acid (1eq., 0.5 mmol) and cyclo­hexyl isocyanide (1eq., 0.5 mmol) were dissolved in DCM (2 mL) and stirred at room temperature for 1 h. After confirming the exclusive formation of the Passerini product (via TLC and LC/MS), the solvent was removed and the crude product was dissolved in DMF (2 mL). Diiso­propyl­amine (DIPEA) (2 eq., 1 mmol, 140 µL) was added and the reaction mixture was heated at 393 K using microwave irradiation for 20 minutes. After cooling and verifying reaction completion (TLC and LC/MS), the crude mixture was directly purified by flash chromatography (EtOAc/hexane 0–100%) using an ISCO TM flash chromatography system to afford 4-(2H-1,3-benzodioxol-5-yl)-N-cyclo­hexyl-5-oxo-3-[4-(tri­fluoro­meth­yl)phen­yl]-2,5-di­hydro­furan-2-carboxamide as a yellow solid (61% yield).

For both compounds, crystals suitable for X-ray structure elucidation were obtained by slow evaporation of a solution of the compound in a mixture of ethyl acetate/hexa­nes (1:3).

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3[link]. Hydrogen atoms were visible in the difference Fourier maps for both structures. The hydrogen atoms bonded to nitro­gen atoms which are involved in hydrogen bonding were placed at positions of the electron density peaks and freely refined. All other hydrogen atoms were placed at calculated positions and allowed to ride on their parent atoms: C—H = 0.98 Å for methyl H atoms and 0.95 Å for other H atoms, with Uiso(H) = 1.5Ueq(C) for methyl H atoms and = 1.2Ueq(C) for other atoms.

Table 3
Experimental details

  (I) (II)
Crystal data
Chemical formula C22H19F4NO4 C25H22F3NO5
Mr 437.38 473.43
Crystal system, space group Monoclinic, P21/c Orthorhombic, Pbca
Temperature (K) 100 100
a, b, c (Å) 8.0173 (8), 24.900 (2), 10.2186 (9) 19.2990 (7), 9.5345 (3), 24.2188 (7)
α, β, γ (°) 90, 96.738 (2), 90 90, 90, 90
V (Å3) 2025.9 (3) 4456.4 (2)
Z 4 8
Radiation type Mo Kα Mo Kα
μ (mm−1) 0.12 0.12
Crystal size (mm) 0.3 × 0.2 × 0.2 0.35 × 0.25 × 0.2
 
Data collection
Diffractometer Bruker APEXII CCD Bruker APEXII CCD
Absorption correction Multi-scan (SADABS; Bruker, 2009[Bruker (2009). APEX2, SAINT, and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Multi-scan (SADABS; Bruker, 2012[Bruker (2012). APEX2, SAINT, and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.589, 0.746 0.609, 0.745
No. of measured, independent and observed [I > 2σ(I)] reflections 16716, 4139, 3698 36729, 3939, 3383
Rint 0.022 0.033
(sin θ/λ)max (Å−1) 0.625 0.595
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.034, 0.084, 1.03 0.035, 0.086, 1.05
No. of reflections 4139 3939
No. of parameters 287 324
No. of restraints 0 30
H-atom treatment H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.31, −0.32 0.27, −0.36
Computer programs: APEX2 and SAINT (Bruker, 2009[Bruker (2009). APEX2, SAINT, and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.], 2012[Bruker (2012). APEX2, SAINT, and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2014 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]), OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]) and OLEX.SOLVE (Bourhis et al., 2015[Bourhis, L. J., Dolomanov, O. V., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2015). Acta Cryst. A71, 59-75.]).

In (II)[link], the tri­fluoro­methyl substituent is disordered over two sets of sites with refined occupancies of 0.751 (3) and 0.249 (3). The disorder does not correspond to the expected rotational disorder of the –CF3 group, but rather consists of a deviation, in the minor component, of the central carbon atom out of the plane of the aromatic ring.

Supporting information

CCDC references: 1043839; 1043838

Crystal structure: contains datablocks I, II, New_Global_Publ_Block. DOI: 10.1107/S2056989015000936/lh5745sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S2056989015000936/lh5745Isup2.hkl

Structure factors: contains datablock II. DOI: 10.1107/S2056989015000936/lh5745IIsup3.hkl

Supporting information file. DOI: 10.1107/S2056989015000936/lh5745Isup4.cml

Supporting information file. DOI: 10.1107/S2056989015000936/lh5745IIsup5.cml

checkCIF report


Chemical context top

Butenolides, also known as furan-2(5H)-ones or furan­ones, are a recurrent moiety in more than 13,000 natural products (De Souza, 2005) and possess different assorted biological applications, exemplified by cytotoxic (Jung et al., 1990) and anti­biotic (Sikorska et al., 2012) activities. Likewise, the butenolide derivative Vioxx® is a potent NSAID (non-steroidal anti-inflammatory drug) used for the relief of pain and inflammation (Prasit et al., 1999) before it was withdrawn from the market in 2004. As a part of our scientific endeavors to access and mimic the complexity and diversity present in naturally occurring molecular scaffolds, the title compounds were synthesized using a Passerini/Knoevenagel sequence and the crystal structures are reported herein. Other multi-component reaction-based approaches towards furan­ones have been reported, but they use limited starting materials. For example, they use unstable phospho­nates (Beck et al., 2001), aliphatic substituents (Bossio et al., 1993, 1994; Marcaccini et al., 2000), or tri­carbonyl inputs (Roßbach et al., 2014).

Structural commentary top

The molecular structures of N-tert-butyl-3-(4-fluoro­phenyl)-5-oxo-4-[2-(tri­fluoro­meth­oxy)­phenyl]-2,5-di­hydro­furan-2-carboxamide (I) (Fig. 1) and 4-(2H-1,3-benzodioxol-5-yl)-N-cyclo­hexyl-5-oxo-3-[4-(tri­fluoro­methyl)­phenyl]-2,5-di­hydro­furan-2-carboxamide (II) (Fig. 2) are similar. The molecules are T-shaped, with the major conformational difference being the O1—C—C—O2 torsion angle. In (I), this torsion angle is -178.9 (1)°, whereas in (II), it is 37.7 (2)°. In (II), the amide oxygen atom, O1, is tucked between O2 and H1A, with contact distances to O2 of 2.738 (1) Å and to H1A of 2.54 Å. The central, di­hydro­furan­one ring is nearly planar in both compounds. The r.m.s. deviation of these central rings is 0.015 Å in (I), and 0.027 Å in (II). In (I), the dihedral angle between the furan ring and the p-fluoro substituted benzene ring is 44.66 (4)° and with the tri­fluoro­meth­oxy-substituted benzene ring it is 48.71 (3)°. In (II), the dihedral angle between the furan ring and the p-tri­fluoro­methyl substituted benzene ring is 40.03 (5)° and the dihedral angle with the benzene ring of the benzo[1,3]dioxol-5-yl ring system is 43.06 (6)°. The cyclo­hexane ring of (II) is in a chair conformation.

The –CF3 substituent of (II) is disordered over two sets of sites. In the major component [occupancy = 0.751 (3)], F2A has a close contact to O1 [2.772 (2) Å], which is lengthened to 3.093 (6) Å in the alternate configuration i.e. the minor component. Two hydrogen atoms from symmetry-equivalent molecules flank F3B (H2A, 2.72 Å, and H23, 2.57 Å) and prevent rotational disorder from alleviating the close contact. In the minor component, the –CF3 group deviates from the plane of the aromatic ring, with C25B displaced by 0.36 (1) Å from the mean plane of the aromatic ring.

Supra­molecular features top

In both crystals, N—H···O hydrogen bonds connect the molecules into chains which run, in (I) along the c-axis direction (Table 1), and in (II) along the b-axis direction (Table 2). The hydrogen-bonding graph set is C(4) in both (I) and (II). The partial packing plots of (I) (Fig. 3) and (II) (Fig. 4) illustrate the hydrogen-bonding motifs.

Database survey top

The Cambridge Structural Database (CSD) contains few examples of 3,4,5-substituted furan-2(5H)-ones. A search (CSD Version 5.36, November 2014; Groom & Allen, 2014) found only one other structure with an amide attachment at the position 5 carbon, TIFXIP (Beck et. al, 2001). For TIFXIP, the O1—C—C—O2 torsion angles for the two molecules in the asymmetric unit are -40.1° and 40.4, similar to that found in (II), and The O1···O2 distances are 2.76 and 2.78 Å . When the search is expanded to include molecules with a second organic substituent on the furan 5-carbon, additional structures are found. In six structures, where only one of the substituents is an amide, the O1—C—C—O2 torsional angle is 180° ± 30° (-­150 to 150°). The O1—C—C—O2 torsion angle of -178.8 (1)° found for (I) falls in this range.

Synthesis and crystallization top

Compound (I): 4-fluoro­phenyl­glyoxal (1 eq., 0.5 mmol), 2 tri­fluoro­meth­oxy-phenyl­acetic acid (1 eq., 0.5 mmol) and tert-butyl isocyanide (1eq., 0.5 mmol) were dissolved in DCM (2 mL) and stirred at room temperature for 1 hour. After confirming the exclusive formation of the Passerini product (via TLC and LC/MS), the solvent was removed and the crude product was dissolved in DMF (2 mL). Diiso­propyl­amine (DIPEA) (2 eq., 1 mmol, 140 µL) was added and the reaction mixture was heated at 393 K using microwave irradiation for 20 minutes. After cooling and verifying reaction completion (TLC and LC/MS), the crude mixture was directly purified by flash chromatography (EtOAc/hexane 0–100%) using an ISCO TM flash chromatography system to afford N-tert-butyl-3-(4-fluoro­phenyl)-5-oxo-4-[2-(tri­fluoro­meth­oxy)­phenyl]-2,5-di­hydro­furan-2-carboxamide as a beige solid (67% yield).

Compound (II): 4-tri­fluoro­methyl­phenyl­glyoxal (1 eq., 0.5 mmol), 3,4-methyl­ene­dioxy­phenyl­acetic acid (1eq., 0.5 mmol) and cyclo­hexyl isocyanide (1eq., 0.5 mmol) were dissolved in DCM (2 mL) and stirred at room temperature for 1 hour. After confirming the exclusive formation of the Passerini product (via TLC and LC/MS), the solvent was removed and the crude product was dissolved in DMF (2 mL). Diiso­propyl­amine (DIPEA) (2 eq., 1 mmol, 140 µL) was added and the reaction mixture was heated at 393 K using microwave irradiation for 20 minutes. After cooling and verifying reaction completion (TLC and LC/MS), the crude mixture was directly purified by flash chromatography (EtOAc/hexane 0–100%) using an ISCO TM flash chromatography system to afford 4-(2H-1,3-benzodioxol-5-yl)-N-cyclo­hexyl-5-oxo-3-[4-(tri­fluoro­methyl)­phenyl]-2,5-di­hydro­furan-2-carboxamide as a yellow solid (61% yield).

For both compounds, crystals suitable for X-ray structure elucidation were obtained by slow evaporation of a solution of the compound in a mixture of ethyl acetate/hexanes (1:3).

Refinement top

Crystal data, data collection and structure refinement details are summarized in Table 2. Hydrogen atoms were visible in the difference Fourier maps for both structures. The hydrogen atoms bonded to nitro­gen atoms which are involved in hydrogen bonding were placed at positions of the electron density peaks and refined without constraints. All other hydrogen atoms were placed at calculated positions and allowed to ride on their parent atoms. For riding hydrogen atoms, bond distances were restrained to 0.95 Å, except for methyl hydrogen atoms for which the C—H distance constrained to 0.98 Å. For riding hydrogen atoms, Uiso(H) was set at 1.5Ueq(C) for methyl H atoms and 1.2Ueq(C) for all other atoms.

In (II), the tri­fluoro­methyl substituent is disordered over two sets of sites with refined occupancies of 0.751 (3) and 0.249 (3). The disorder does not correspond to the expected rotational disorder of the –CF3 group, but rather consists of a deviation, in the minor component, of the central carbon atom out of the plane of the aromatic ring.

Related literature top

For related literature, see: Bossio et al. (1993, 1994); De Souza (2005); Groom & Allen (2014); Jung et al. (1990); Marcaccini et al. (2000); Prasit et al. (1999); Roßbach, Harms & Koert (2014); Sikorska et al. (2012); Beck et al. (2001).

Computing details top

Data collection: APEX2 (Bruker, 2009) for (I); APEX2 (Bruker, 2012) for (II). Cell refinement: SAINT (Bruker, 2009) for (I); SAINT (Bruker, 2012) for (II). Data reduction: SAINT (Bruker, 2009) for (I); SAINT (Bruker, 2012) for (II). Program(s) used to solve structure: SHELXS97 (Sheldrick, 2008) for (I); OLEX.SOLVE (Bourhis et al., 2015) for (II). For both compounds, program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I). Anisotropically refined atoms are shown as 50% probability displacement ellipsoids.
[Figure 2] Fig. 2. The molecular structure of (II). The –CF3 substituent is disordered and only the major component is shown. Anisotropically refined atoms are shown as 50% probability displacement ellipsoids.
[Figure 3] Fig. 3. Part of the crystal structure of (I) viewed along [100]. The hydrogen bonds linking the molecules into chains along [001] are shown as dotted lines.
[Figure 4] Fig. 4. A hydrogen-bonded chain of molecules of (II) propagating along [010]. Hydrogen bonds are shown as dotted lines.
(I) N-tert-Butyl-3-(4-fluorophenyl)-5-oxo-4-[2-(trifluoromethoxy)phenyl]-2,5-dihydrofuran-2-carboxamide top
Crystal data top
C22H19F4NO4F(000) = 904
Mr = 437.38Dx = 1.434 Mg m−3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 8.0173 (8) ÅCell parameters from 9193 reflections
b = 24.900 (2) Åθ = 2.6–28.2°
c = 10.2186 (9) ŵ = 0.12 mm−1
β = 96.738 (2)°T = 100 K
V = 2025.9 (3) Å3Prism, clear colourless
Z = 40.3 × 0.2 × 0.2 mm
Data collection top
Bruker APEXII CCD
diffractometer		4139 independent reflections
Radiation source: sealed tube3698 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.022
Detector resolution: 8 pixels mm-1θmax = 26.4°, θmin = 1.6°
ω and ϕ scansh = −9→10
Absorption correction: multi-scan
(SADABS; Bruker, 2009)		k = −31→31
Tmin = 0.589, Tmax = 0.746l = −12→12
16716 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.034Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.084H atoms treated by a mixture of independent and constrained refinement
S = 1.03 w = 1/[σ2(Fo2) + (0.0363P)2 + 1.005P]
where P = (Fo2 + 2Fc2)/3
4139 reflections(Δ/σ)max = 0.001
287 parametersΔρmax = 0.31 e Å−3
0 restraintsΔρmin = −0.32 e Å−3
Crystal data top
C22H19F4NO4V = 2025.9 (3) Å3
Mr = 437.38Z = 4
Monoclinic, P21/cMo Kα radiation
a = 8.0173 (8) ŵ = 0.12 mm−1
b = 24.900 (2) ÅT = 100 K
c = 10.2186 (9) Å0.3 × 0.2 × 0.2 mm
β = 96.738 (2)°
Data collection top
Bruker APEXII CCD
diffractometer		4139 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2009)		3698 reflections with I > 2σ(I)
Tmin = 0.589, Tmax = 0.746Rint = 0.022
16716 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0340 restraints
wR(F2) = 0.084H atoms treated by a mixture of independent and constrained refinement
S = 1.03Δρmax = 0.31 e Å−3
4139 reflectionsΔρmin = −0.32 e Å−3
287 parameters
Special details top

Experimental. Absorption correction: SADABS-2008/1 (Bruker, 2009) was used for absorption correction. wR2(int) was 0.0543 before and 0.0350 after correction. The Ratio of minimum to maximum transmission is 0.7899. The λ/2 correction factor is 0.0015.

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 (Å2) top
xyzUiso*/Ueq
F10.41272 (11)0.45346 (3)0.87343 (7)0.0292 (2)
F2−0.18072 (11)0.38769 (4)0.50333 (9)0.0362 (2)
O10.49555 (11)0.26340 (4)0.55486 (8)0.01916 (19)
O30.17815 (11)0.32454 (4)0.06255 (8)0.0216 (2)
O40.01276 (11)0.43064 (4)0.41800 (8)0.0204 (2)
F3−0.16303 (13)0.37653 (4)0.29712 (9)0.0449 (3)
O20.23911 (11)0.27391 (3)0.24391 (8)0.01759 (19)
F4−0.25704 (12)0.45026 (4)0.36505 (14)0.0611 (4)
N10.53587 (13)0.23207 (4)0.35123 (10)0.0163 (2)
C70.27384 (14)0.34306 (5)0.39881 (12)0.0153 (2)
C30.27935 (16)0.38083 (5)0.75683 (12)0.0198 (3)
H30.23400.36930.83390.024*
C10.31213 (15)0.37069 (5)0.52612 (11)0.0153 (2)
C20.24707 (15)0.35278 (5)0.63949 (12)0.0175 (3)
H20.18030.32120.63600.021*
C50.44905 (16)0.44430 (5)0.65007 (12)0.0190 (3)
H50.51970.47500.65550.023*
C180.45164 (15)0.25822 (5)0.43641 (12)0.0151 (2)
C60.41299 (15)0.41644 (5)0.53279 (12)0.0167 (2)
H60.45760.42870.45600.020*
C90.21170 (15)0.32210 (5)0.18045 (12)0.0166 (2)
C120.25614 (16)0.44545 (5)0.13706 (12)0.0195 (3)
H120.33020.42540.08980.023*
C110.18971 (15)0.42177 (5)0.24354 (12)0.0163 (2)
C80.28161 (15)0.28284 (5)0.38281 (11)0.0156 (2)
H80.19250.26620.43040.019*
C100.22884 (15)0.36535 (5)0.28033 (12)0.0159 (2)
C40.37925 (16)0.42599 (5)0.75857 (12)0.0196 (3)
C130.21580 (17)0.49790 (5)0.09903 (13)0.0221 (3)
H130.26160.51320.02600.027*
C160.08092 (15)0.45302 (5)0.30855 (12)0.0171 (2)
C190.70069 (15)0.20563 (5)0.38884 (12)0.0178 (3)
C210.68968 (18)0.16575 (6)0.50104 (13)0.0257 (3)
H21A0.66570.18510.58020.038*
H21B0.79670.14660.51940.038*
H21C0.59960.13990.47550.038*
C150.04164 (16)0.50550 (5)0.27394 (13)0.0210 (3)
H15−0.03030.52600.32220.025*
C200.83339 (17)0.24854 (6)0.42715 (15)0.0275 (3)
H20A0.84650.27110.35050.041*
H20B0.94070.23120.45760.041*
H20C0.79810.27080.49800.041*
C140.10909 (17)0.52781 (5)0.16737 (13)0.0231 (3)
H140.08200.56370.14130.028*
C17−0.14429 (17)0.41192 (6)0.39516 (14)0.0269 (3)
C220.74529 (18)0.17542 (6)0.26798 (13)0.0257 (3)
H22A0.66150.14740.24420.039*
H22B0.85640.15900.28780.039*
H22C0.74670.20050.19420.039*
H10.496 (2)0.2324 (6)0.2709 (17)0.025 (4)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0373 (5)0.0339 (5)0.0166 (4)−0.0029 (4)0.0044 (3)−0.0100 (3)
F20.0381 (5)0.0359 (5)0.0385 (5)−0.0004 (4)0.0206 (4)0.0091 (4)
O10.0201 (4)0.0233 (5)0.0138 (4)0.0021 (4)0.0008 (3)−0.0012 (3)
O30.0243 (5)0.0250 (5)0.0144 (4)0.0033 (4)−0.0023 (4)−0.0031 (4)
O40.0208 (5)0.0241 (5)0.0172 (4)0.0033 (4)0.0067 (3)0.0007 (4)
F30.0480 (6)0.0522 (6)0.0339 (5)−0.0246 (5)0.0014 (4)−0.0021 (4)
O20.0184 (4)0.0176 (4)0.0157 (4)0.0014 (3)−0.0022 (3)−0.0030 (3)
F40.0230 (5)0.0470 (6)0.1169 (10)0.0145 (4)0.0228 (6)0.0425 (6)
N10.0167 (5)0.0192 (5)0.0124 (5)0.0032 (4)−0.0008 (4)−0.0003 (4)
C70.0115 (5)0.0179 (6)0.0169 (6)0.0009 (4)0.0043 (4)0.0000 (5)
C30.0215 (6)0.0243 (6)0.0143 (6)0.0048 (5)0.0055 (5)0.0030 (5)
C10.0147 (6)0.0173 (6)0.0140 (6)0.0045 (5)0.0019 (4)−0.0002 (4)
C20.0175 (6)0.0174 (6)0.0179 (6)0.0019 (5)0.0029 (5)0.0025 (5)
C50.0187 (6)0.0182 (6)0.0198 (6)0.0005 (5)0.0009 (5)−0.0015 (5)
C180.0151 (6)0.0137 (5)0.0162 (6)−0.0018 (4)0.0012 (4)0.0007 (4)
C60.0167 (6)0.0195 (6)0.0142 (6)0.0026 (5)0.0028 (5)0.0023 (5)
C90.0117 (6)0.0195 (6)0.0183 (6)0.0026 (4)0.0004 (4)−0.0014 (5)
C120.0199 (6)0.0233 (6)0.0152 (6)0.0002 (5)0.0014 (5)−0.0013 (5)
C110.0161 (6)0.0189 (6)0.0131 (6)0.0001 (5)−0.0017 (4)−0.0017 (4)
C80.0145 (6)0.0186 (6)0.0135 (6)−0.0008 (5)0.0010 (4)−0.0018 (5)
C100.0128 (6)0.0202 (6)0.0150 (6)0.0009 (5)0.0030 (4)−0.0023 (5)
C40.0223 (6)0.0233 (6)0.0130 (6)0.0051 (5)0.0001 (5)−0.0047 (5)
C130.0252 (7)0.0234 (7)0.0174 (6)−0.0043 (5)0.0007 (5)0.0023 (5)
C160.0166 (6)0.0211 (6)0.0133 (6)−0.0012 (5)0.0002 (5)−0.0009 (5)
C190.0155 (6)0.0203 (6)0.0172 (6)0.0040 (5)0.0009 (5)0.0008 (5)
C210.0267 (7)0.0273 (7)0.0231 (7)0.0074 (6)0.0034 (5)0.0070 (6)
C150.0207 (6)0.0199 (6)0.0217 (6)0.0027 (5)0.0002 (5)−0.0040 (5)
C200.0171 (6)0.0282 (7)0.0370 (8)0.0009 (5)0.0020 (6)−0.0023 (6)
C140.0270 (7)0.0169 (6)0.0241 (7)−0.0008 (5)−0.0025 (5)0.0009 (5)
C170.0234 (7)0.0245 (7)0.0338 (8)0.0037 (5)0.0074 (6)0.0079 (6)
C220.0255 (7)0.0302 (7)0.0214 (7)0.0117 (6)0.0030 (5)−0.0008 (5)
Geometric parameters (Å, º) top
F1—C41.3578 (14)C6—H60.9500
F2—C171.3217 (16)C9—C101.4791 (17)
O1—C181.2271 (15)C12—H120.9500
O3—C91.2047 (15)C12—C111.3968 (17)
O4—C161.4154 (14)C12—C131.3900 (18)
O4—C171.3373 (17)C11—C101.4784 (17)
F3—C171.3294 (18)C11—C161.3942 (17)
O2—C91.3694 (15)C8—H81.0000
O2—C81.4376 (14)C13—H130.9500
F4—C171.3257 (17)C13—C141.3836 (19)
N1—C181.3326 (15)C16—C151.3804 (18)
N1—C191.4860 (16)C19—C211.5272 (17)
N1—H10.845 (17)C19—C201.5262 (19)
C7—C11.4720 (16)C19—C221.5240 (17)
C7—C81.5104 (16)C21—H21A0.9800
C7—C101.3423 (17)C21—H21B0.9800
C3—H30.9500C21—H21C0.9800
C3—C21.3855 (18)C15—H150.9500
C3—C41.3795 (19)C15—C141.3875 (19)
C1—C21.3982 (17)C20—H20A0.9800
C1—C61.3940 (17)C20—H20B0.9800
C2—H20.9500C20—H20C0.9800
C5—H50.9500C14—H140.9500
C5—C61.3856 (17)C22—H22A0.9800
C5—C41.3768 (18)C22—H22B0.9800
C18—C81.5358 (17)C22—H22C0.9800
C17—O4—C16116.25 (10)F1—C4—C5118.14 (12)
C9—O2—C8109.78 (9)C5—C4—C3123.35 (12)
C18—N1—C19123.44 (10)C12—C13—H13119.9
C18—N1—H1118.0 (11)C14—C13—C12120.14 (12)
C19—N1—H1118.4 (11)C14—C13—H13119.9
C1—C7—C8123.57 (10)C11—C16—O4118.55 (11)
C10—C7—C1127.58 (11)C15—C16—O4118.52 (11)
C10—C7—C8108.85 (10)C15—C16—C11122.89 (11)
C2—C3—H3120.9N1—C19—C21110.75 (10)
C4—C3—H3120.9N1—C19—C20109.16 (10)
C4—C3—C2118.12 (11)N1—C19—C22107.17 (10)
C2—C1—C7121.58 (11)C20—C19—C21111.26 (11)
C6—C1—C7119.01 (10)C22—C19—C21109.10 (11)
C6—C1—C2119.40 (11)C22—C19—C20109.31 (11)
C3—C2—C1120.41 (12)C19—C21—H21A109.5
C3—C2—H2119.8C19—C21—H21B109.5
C1—C2—H2119.8C19—C21—H21C109.5
C6—C5—H5121.1H21A—C21—H21B109.5
C4—C5—H5121.1H21A—C21—H21C109.5
C4—C5—C6117.87 (12)H21B—C21—H21C109.5
O1—C18—N1125.94 (11)C16—C15—H15120.6
O1—C18—C8116.73 (10)C16—C15—C14118.81 (12)
N1—C18—C8117.31 (10)C14—C15—H15120.6
C1—C6—H6119.6C19—C20—H20A109.5
C5—C6—C1120.82 (11)C19—C20—H20B109.5
C5—C6—H6119.6C19—C20—H20C109.5
O3—C9—O2121.49 (11)H20A—C20—H20B109.5
O3—C9—C10130.18 (12)H20A—C20—H20C109.5
O2—C9—C10108.33 (10)H20B—C20—H20C109.5
C11—C12—H12119.4C13—C14—C15120.10 (12)
C13—C12—H12119.4C13—C14—H14119.9
C13—C12—C11121.13 (12)C15—C14—H14119.9
C12—C11—C10120.68 (11)F2—C17—O4108.01 (12)
C16—C11—C12116.91 (11)F2—C17—F3108.13 (12)
C16—C11—C10122.36 (11)F2—C17—F4108.14 (12)
O2—C8—C7104.62 (9)F3—C17—O4112.54 (11)
O2—C8—C18112.83 (9)F4—C17—O4113.07 (12)
O2—C8—H8108.5F4—C17—F3106.78 (13)
C7—C8—C18113.81 (10)C19—C22—H22A109.5
C7—C8—H8108.5C19—C22—H22B109.5
C18—C8—H8108.5C19—C22—H22C109.5
C7—C10—C9108.34 (11)H22A—C22—H22B109.5
C7—C10—C11130.46 (11)H22A—C22—H22C109.5
C11—C10—C9121.11 (11)H22B—C22—H22C109.5
F1—C4—C3118.51 (11)
O1—C18—C8—O2−178.85 (10)C12—C13—C14—C15−0.2 (2)
O1—C18—C8—C762.13 (14)C11—C12—C13—C140.44 (19)
O3—C9—C10—C7−177.73 (13)C11—C16—C15—C141.98 (19)
O3—C9—C10—C115.3 (2)C8—O2—C9—O3178.20 (11)
O4—C16—C15—C14179.50 (11)C8—O2—C9—C10−2.52 (12)
O2—C9—C10—C73.08 (13)C8—C7—C1—C2−46.08 (17)
O2—C9—C10—C11−173.85 (10)C8—C7—C1—C6135.23 (12)
N1—C18—C8—O2−0.55 (15)C8—C7—C10—C9−2.32 (13)
N1—C18—C8—C7−119.57 (11)C8—C7—C10—C11174.22 (12)
C7—C1—C2—C3−177.29 (11)C10—C7—C1—C2134.48 (13)
C7—C1—C6—C5178.60 (11)C10—C7—C1—C6−44.22 (18)
C1—C7—C8—O2−178.70 (10)C10—C7—C8—O20.83 (12)
C1—C7—C8—C18−55.10 (15)C10—C7—C8—C18124.44 (11)
C1—C7—C10—C9177.19 (11)C10—C11—C16—O43.38 (17)
C1—C7—C10—C11−6.3 (2)C10—C11—C16—C15−179.09 (12)
C2—C3—C4—F1−179.44 (11)C4—C3—C2—C1−1.13 (18)
C2—C3—C4—C5−0.42 (19)C4—C5—C6—C1−1.35 (18)
C2—C1—C6—C5−0.12 (18)C13—C12—C11—C10177.90 (11)
C18—N1—C19—C2155.13 (15)C13—C12—C11—C160.44 (18)
C18—N1—C19—C20−67.70 (15)C16—O4—C17—F2173.52 (10)
C18—N1—C19—C22174.03 (11)C16—O4—C17—F354.24 (15)
C6—C1—C2—C31.39 (18)C16—O4—C17—F4−66.86 (15)
C6—C5—C4—F1−179.33 (11)C16—C11—C10—C7−48.09 (19)
C6—C5—C4—C31.65 (19)C16—C11—C10—C9128.08 (13)
C9—O2—C8—C71.13 (12)C16—C15—C14—C13−1.01 (19)
C9—O2—C8—C18−123.11 (10)C19—N1—C18—O1−1.11 (19)
C12—C11—C10—C7134.59 (14)C19—N1—C18—C8−179.23 (10)
C12—C11—C10—C9−49.24 (16)C17—O4—C16—C11−100.23 (13)
C12—C11—C16—O4−179.20 (11)C17—O4—C16—C1582.14 (14)
C12—C11—C16—C15−1.67 (18)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.845 (17)2.209 (17)3.0098 (14)158.2 (15)
Symmetry code: (i) x, −y+1/2, z−1/2.
(II) 4-(2H-1,3-Benzodioxol-5-yl)-N-cyclohexyl-5-oxo-3-[4-(trifluoromethyl)phenyl]-2,5-dihydrofuran-2-carboxamide top
Crystal data top
C25H22F3NO5Dx = 1.411 Mg m−3
Mr = 473.43Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, PbcaCell parameters from 9996 reflections
a = 19.2990 (7) Åθ = 2.5–25.6°
b = 9.5345 (3) ŵ = 0.12 mm−1
c = 24.2188 (7) ÅT = 100 K
V = 4456.4 (2) Å3Prism, clear colourless
Z = 80.35 × 0.25 × 0.2 mm
F(000) = 1968
Data collection top
Bruker APEXII CCD
diffractometer		3939 independent reflections
Radiation source: sealed tube3383 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.033
Detector resolution: 8 pixels mm-1θmax = 25.0°, θmin = 1.7°
ϕ and ω scansh = −18→22
Absorption correction: multi-scan
(SADABS; Bruker, 2012)		k = −11→11
Tmin = 0.609, Tmax = 0.745l = −28→28
36729 measured reflections
Refinement top
Refinement on F2Primary atom site location: iterative
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.035H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.086 w = 1/[σ2(Fo2) + (0.0329P)2 + 2.7716P]
where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max = 0.001
3939 reflectionsΔρmax = 0.27 e Å−3
324 parametersΔρmin = −0.36 e Å−3
30 restraints
Crystal data top
C25H22F3NO5V = 4456.4 (2) Å3
Mr = 473.43Z = 8
Orthorhombic, PbcaMo Kα radiation
a = 19.2990 (7) ŵ = 0.12 mm−1
b = 9.5345 (3) ÅT = 100 K
c = 24.2188 (7) Å0.35 × 0.25 × 0.2 mm
Data collection top
Bruker APEXII CCD
diffractometer		3939 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2012)		3383 reflections with I > 2σ(I)
Tmin = 0.609, Tmax = 0.745Rint = 0.033
36729 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.03530 restraints
wR(F2) = 0.086H atoms treated by a mixture of independent and constrained refinement
S = 1.05Δρmax = 0.27 e Å−3
3939 reflectionsΔρmin = −0.36 e Å−3
324 parameters
Special details top

Experimental. SADABS-2012/1 (Bruker,2012) was used for absorption correction. wR2(int) was 0.0555 before and 0.0466 after correction. The Ratio of minimum to maximum transmission is 0.8167. The λ/2 correction factor is 0.0015.

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
O10.75295 (5)0.55806 (10)0.49296 (4)0.0185 (2)
O20.80402 (5)0.43446 (10)0.39940 (4)0.0172 (2)
O30.81211 (6)0.58478 (12)0.32882 (4)0.0255 (3)
O40.51011 (6)0.45837 (13)0.21882 (5)0.0367 (3)
F3B0.4051 (13)0.082 (2)0.4558 (11)0.0458 (10)0.249 (3)
O50.52165 (7)0.69044 (14)0.19298 (5)0.0384 (3)
N10.72446 (7)0.34318 (13)0.52641 (5)0.0165 (3)
F1B0.4084 (4)0.2249 (7)0.5233 (3)0.0499 (6)0.249 (3)
C70.74426 (7)0.43101 (14)0.48714 (6)0.0140 (3)
C190.61606 (7)0.35359 (15)0.41728 (5)0.0144 (3)
C80.74979 (7)0.36625 (15)0.42917 (5)0.0145 (3)
H80.75760.26270.43120.017*
C90.68437 (7)0.40034 (14)0.39745 (6)0.0144 (3)
C240.60782 (8)0.21905 (15)0.43879 (6)0.0173 (3)
H240.64600.15610.43930.021*
C110.77610 (8)0.51128 (15)0.35706 (6)0.0175 (3)
C200.55997 (8)0.44519 (15)0.41735 (6)0.0199 (3)
H200.56510.53710.40270.024*
C120.65547 (8)0.54436 (15)0.31161 (6)0.0173 (3)
C100.70054 (7)0.48558 (15)0.35506 (6)0.0156 (3)
C170.56398 (8)0.51889 (17)0.24760 (6)0.0244 (4)
C150.57085 (9)0.65775 (18)0.23231 (6)0.0268 (4)
C230.54458 (8)0.17701 (16)0.45938 (6)0.0217 (3)
H230.53900.08470.47340.026*
C140.61954 (9)0.74357 (18)0.25555 (7)0.0295 (4)
H140.62390.83920.24510.035*
C220.48935 (8)0.26896 (17)0.45959 (7)0.0261 (4)
C130.66266 (8)0.68364 (16)0.29549 (6)0.0230 (3)
H130.69780.73940.31200.028*
C10.69989 (8)0.38852 (15)0.58066 (6)0.0198 (3)
H1A0.68280.48710.57700.024*
C20.75650 (10)0.38768 (19)0.62406 (6)0.0313 (4)
H2A0.79440.45150.61270.038*
H2B0.77590.29200.62760.038*
C210.49677 (8)0.40313 (17)0.43866 (7)0.0273 (4)
H210.45860.46610.43890.033*
C180.60503 (8)0.45830 (16)0.28706 (6)0.0209 (3)
H180.59970.36270.29730.025*
C60.63867 (9)0.29746 (18)0.59757 (6)0.0304 (4)
H6A0.65350.19810.59920.036*
H6B0.60160.30530.56950.036*
C50.61007 (11)0.3418 (2)0.65399 (7)0.0414 (5)
H5A0.58940.43660.65110.050*
H5B0.57310.27590.66540.050*
C25B0.4193 (8)0.2164 (15)0.4674 (5)0.0359 (9)0.249 (3)
C30.72705 (11)0.4350 (2)0.67971 (7)0.0413 (5)
H3A0.76390.43070.70810.050*
H3B0.71130.53360.67680.050*
C40.66675 (12)0.3431 (2)0.69726 (7)0.0461 (5)
H4A0.68350.24620.70340.055*
H4B0.64760.37840.73260.055*
C160.49374 (10)0.5578 (2)0.17675 (7)0.0384 (5)
H16A0.44290.56490.17220.046*
H16B0.51410.52810.14110.046*
F2B0.3664 (3)0.2895 (6)0.4465 (4)0.0671 (8)0.249 (3)
C25A0.4240 (2)0.2222 (4)0.48835 (13)0.0359 (9)0.751 (3)
F1A0.43368 (11)0.1921 (2)0.54261 (8)0.0499 (6)0.751 (3)
F2A0.37403 (9)0.31660 (19)0.48644 (14)0.0671 (8)0.751 (3)
F3A0.4005 (4)0.1032 (6)0.4662 (3)0.0458 (10)0.751 (3)
H10.7263 (8)0.2588 (19)0.5199 (6)0.016 (4)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0213 (6)0.0130 (5)0.0212 (5)−0.0007 (4)0.0009 (4)−0.0008 (4)
O20.0135 (5)0.0206 (5)0.0175 (5)−0.0016 (4)0.0016 (4)0.0006 (4)
O30.0224 (6)0.0336 (6)0.0206 (6)−0.0079 (5)0.0041 (5)0.0053 (5)
O40.0344 (7)0.0465 (8)0.0292 (6)−0.0087 (6)−0.0167 (5)0.0072 (6)
F3B0.0203 (12)0.034 (2)0.083 (3)−0.0092 (14)0.0007 (16)0.0106 (14)
O50.0378 (7)0.0447 (8)0.0327 (7)0.0069 (6)−0.0141 (6)0.0109 (6)
N10.0240 (7)0.0106 (6)0.0149 (6)0.0013 (5)−0.0005 (5)−0.0006 (5)
F1B0.0493 (13)0.0453 (11)0.0550 (13)0.0014 (9)0.0319 (10)0.0147 (8)
C70.0101 (7)0.0137 (7)0.0182 (7)0.0018 (6)−0.0030 (6)−0.0005 (6)
C190.0149 (7)0.0175 (7)0.0108 (6)−0.0009 (6)−0.0018 (6)−0.0013 (5)
C80.0132 (7)0.0139 (7)0.0164 (7)−0.0011 (6)0.0023 (6)0.0003 (6)
C90.0165 (7)0.0127 (7)0.0140 (7)0.0001 (6)−0.0005 (6)−0.0041 (6)
C240.0149 (7)0.0178 (7)0.0191 (7)0.0017 (6)0.0001 (6)0.0002 (6)
C110.0205 (8)0.0181 (7)0.0137 (7)−0.0008 (6)0.0021 (6)−0.0024 (6)
C200.0198 (8)0.0172 (7)0.0226 (8)0.0012 (6)0.0005 (6)0.0042 (6)
C120.0185 (8)0.0209 (8)0.0126 (7)0.0003 (6)0.0023 (6)−0.0001 (6)
C100.0185 (8)0.0151 (7)0.0133 (7)−0.0013 (6)0.0011 (6)−0.0028 (6)
C170.0214 (8)0.0334 (9)0.0185 (7)−0.0024 (7)−0.0018 (6)−0.0002 (7)
C150.0261 (9)0.0344 (9)0.0201 (8)0.0080 (7)−0.0027 (7)0.0059 (7)
C230.0209 (8)0.0170 (8)0.0273 (8)−0.0013 (6)0.0031 (7)0.0030 (6)
C140.0353 (10)0.0230 (8)0.0303 (9)0.0041 (7)−0.0007 (8)0.0073 (7)
C220.0163 (8)0.0231 (8)0.0388 (9)−0.0007 (7)0.0068 (7)0.0018 (7)
C130.0271 (9)0.0214 (8)0.0204 (8)−0.0020 (7)−0.0011 (7)−0.0003 (6)
C10.0297 (9)0.0151 (7)0.0144 (7)0.0025 (6)0.0009 (6)0.0002 (6)
C20.0414 (11)0.0311 (9)0.0215 (8)0.0004 (8)−0.0080 (8)0.0002 (7)
C210.0175 (8)0.0232 (8)0.0412 (10)0.0052 (7)0.0038 (7)0.0036 (7)
C180.0241 (9)0.0228 (8)0.0157 (7)−0.0019 (7)−0.0003 (6)0.0022 (6)
C60.0400 (10)0.0301 (9)0.0211 (8)−0.0063 (8)0.0055 (7)−0.0023 (7)
C50.0561 (13)0.0432 (11)0.0248 (9)−0.0085 (10)0.0160 (9)−0.0013 (8)
C25B0.0282 (13)0.0283 (11)0.051 (3)0.0034 (9)0.023 (2)0.008 (2)
C30.0624 (14)0.0431 (11)0.0183 (8)0.0009 (10)−0.0093 (8)−0.0028 (8)
C40.0841 (16)0.0385 (11)0.0156 (8)0.0002 (11)0.0074 (9)0.0039 (8)
C160.0328 (10)0.0533 (12)0.0290 (9)0.0027 (9)−0.0123 (8)0.0072 (9)
F2B0.0218 (7)0.0383 (9)0.141 (2)0.0111 (7)0.0384 (13)0.0238 (13)
C25A0.0282 (13)0.0283 (11)0.051 (3)0.0034 (9)0.023 (2)0.008 (2)
F1A0.0493 (13)0.0453 (11)0.0550 (13)0.0014 (9)0.0319 (10)0.0147 (8)
F2A0.0218 (7)0.0383 (9)0.141 (2)0.0111 (7)0.0384 (13)0.0238 (13)
F3A0.0203 (12)0.034 (2)0.083 (3)−0.0092 (14)0.0007 (16)0.0106 (14)
Geometric parameters (Å, º) top
O1—C71.2310 (16)C23—C221.380 (2)
O2—C81.4276 (17)C14—H140.9500
O2—C111.3704 (17)C14—C131.398 (2)
O3—C111.2008 (18)C22—C211.383 (2)
O4—C171.3784 (19)C22—C25B1.455 (16)
O4—C161.427 (2)C22—C25A1.507 (4)
F3B—C25B1.342 (17)C13—H130.9500
O5—C151.3807 (19)C1—H1A1.0000
O5—C161.429 (2)C1—C21.516 (2)
N1—C71.3234 (18)C1—C61.522 (2)
N1—C11.4624 (18)C2—H2A0.9900
N1—H10.821 (18)C2—H2B0.9900
F1B—C25B1.371 (11)C2—C31.531 (2)
C7—C81.5375 (19)C21—H210.9500
C19—C91.472 (2)C18—H180.9500
C19—C241.394 (2)C6—H6A0.9900
C19—C201.391 (2)C6—H6B0.9900
C8—H81.0000C6—C51.533 (2)
C8—C91.5131 (19)C5—H5A0.9900
C9—C101.346 (2)C5—H5B0.9900
C24—H240.9500C5—C41.515 (3)
C24—C231.378 (2)C25B—F2B1.336 (14)
C11—C101.480 (2)C3—H3A0.9900
C20—H200.9500C3—H3B0.9900
C20—C211.384 (2)C3—C41.518 (3)
C12—C101.476 (2)C4—H4A0.9900
C12—C131.391 (2)C4—H4B0.9900
C12—C181.405 (2)C16—H16A0.9900
C17—C151.381 (2)C16—H16B0.9900
C17—C181.369 (2)C25A—F1A1.358 (4)
C15—C141.367 (2)C25A—F2A1.321 (4)
C23—H230.9500C25A—F3A1.335 (6)
C11—O2—C8109.46 (11)N1—C1—C6108.95 (12)
C17—O4—C16104.46 (13)C2—C1—H1A107.7
C15—O5—C16104.43 (13)C2—C1—C6111.71 (13)
C7—N1—C1123.52 (12)C6—C1—H1A107.7
C7—N1—H1118.0 (11)C1—C2—H2A109.7
C1—N1—H1118.5 (11)C1—C2—H2B109.7
O1—C7—N1125.44 (13)C1—C2—C3109.95 (15)
O1—C7—C8119.35 (12)H2A—C2—H2B108.2
N1—C7—C8114.96 (12)C3—C2—H2A109.7
C24—C19—C9120.19 (13)C3—C2—H2B109.7
C20—C19—C9120.48 (13)C20—C21—H21120.1
C20—C19—C24119.25 (13)C22—C21—C20119.73 (14)
O2—C8—C7109.22 (11)C22—C21—H21120.1
O2—C8—H8111.3C12—C18—H18121.6
O2—C8—C9104.91 (10)C17—C18—C12116.73 (14)
C7—C8—H8111.3C17—C18—H18121.6
C9—C8—C7108.63 (11)C1—C6—H6A109.4
C9—C8—H8111.3C1—C6—H6B109.4
C19—C9—C8121.10 (12)C1—C6—C5111.21 (14)
C10—C9—C19129.72 (13)H6A—C6—H6B108.0
C10—C9—C8108.88 (12)C5—C6—H6A109.4
C19—C24—H24119.9C5—C6—H6B109.4
C23—C24—C19120.27 (14)C6—C5—H5A109.4
C23—C24—H24119.9C6—C5—H5B109.4
O2—C11—C10108.87 (12)H5A—C5—H5B108.0
O3—C11—O2120.71 (13)C4—C5—C6111.02 (17)
O3—C11—C10130.42 (14)C4—C5—H5A109.4
C19—C20—H20119.9C4—C5—H5B109.4
C21—C20—C19120.30 (14)F3B—C25B—F1B103.5 (14)
C21—C20—H20119.9F3B—C25B—C22119.5 (14)
C13—C12—C10120.26 (13)F1B—C25B—C22104.5 (9)
C13—C12—C18120.51 (14)F2B—C25B—F3B105.2 (16)
C18—C12—C10119.23 (13)F2B—C25B—F1B103.1 (10)
C9—C10—C11107.66 (13)F2B—C25B—C22118.8 (11)
C9—C10—C12129.54 (14)C2—C3—H3A109.4
C12—C10—C11122.78 (13)C2—C3—H3B109.4
O4—C17—C15109.76 (14)H3A—C3—H3B108.0
C18—C17—O4127.80 (15)C4—C3—C2111.16 (15)
C18—C17—C15122.41 (15)C4—C3—H3A109.4
O5—C15—C17109.59 (15)C4—C3—H3B109.4
C14—C15—O5128.44 (15)C5—C4—C3111.39 (15)
C14—C15—C17121.96 (15)C5—C4—H4A109.4
C24—C23—H23120.0C5—C4—H4B109.4
C24—C23—C22120.04 (14)C3—C4—H4A109.4
C22—C23—H23120.0C3—C4—H4B109.4
C15—C14—H14121.6H4A—C4—H4B108.0
C15—C14—C13116.70 (15)O4—C16—O5107.95 (13)
C13—C14—H14121.6O4—C16—H16A110.1
C23—C22—C21120.41 (15)O4—C16—H16B110.1
C23—C22—C25B120.0 (6)O5—C16—H16A110.1
C23—C22—C25A117.36 (19)O5—C16—H16B110.1
C21—C22—C25B117.6 (5)H16A—C16—H16B108.4
C21—C22—C25A121.96 (19)F1A—C25A—C22113.3 (3)
C12—C13—C14121.67 (15)F2A—C25A—C22113.2 (3)
C12—C13—H13119.2F2A—C25A—F1A106.1 (3)
C14—C13—H13119.2F2A—C25A—F3A108.4 (5)
N1—C1—H1A107.7F3A—C25A—C22110.5 (4)
N1—C1—C2112.81 (13)F3A—C25A—F1A104.8 (4)
O1—C7—C8—O237.65 (17)C10—C12—C18—C17179.02 (13)
O1—C7—C8—C9−76.25 (16)C17—O4—C16—O5−19.09 (18)
O2—C8—C9—C19−176.88 (12)C17—C15—C14—C130.5 (2)
O2—C8—C9—C10−2.55 (15)C15—O5—C16—O418.95 (18)
O2—C11—C10—C92.98 (15)C15—C17—C18—C12−0.3 (2)
O2—C11—C10—C12−175.42 (12)C15—C14—C13—C12−1.3 (2)
O3—C11—C10—C9−176.73 (15)C23—C22—C21—C200.0 (3)
O3—C11—C10—C124.9 (2)C23—C22—C25B—F3B−22.7 (17)
O4—C17—C15—O5−0.23 (19)C23—C22—C25B—F1B92.3 (9)
O4—C17—C15—C14178.50 (15)C23—C22—C25B—F2B−153.5 (8)
O4—C17—C18—C12−178.10 (15)C23—C22—C25A—F1A59.2 (3)
O5—C15—C14—C13178.93 (16)C23—C22—C25A—F2A−179.9 (2)
N1—C7—C8—O2−147.74 (12)C23—C22—C25A—F3A−58.1 (5)
N1—C7—C8—C998.36 (14)C13—C12—C10—C9137.71 (16)
N1—C1—C2—C3−179.57 (14)C13—C12—C10—C11−44.3 (2)
N1—C1—C6—C5−179.20 (14)C13—C12—C18—C17−0.6 (2)
C7—N1—C1—C2−95.91 (17)C1—N1—C7—O19.6 (2)
C7—N1—C1—C6139.43 (14)C1—N1—C7—C8−164.62 (13)
C7—C8—C9—C19−60.19 (16)C1—C2—C3—C456.9 (2)
C7—C8—C9—C10114.14 (13)C1—C6—C5—C4−54.2 (2)
C19—C9—C10—C11173.54 (14)C2—C1—C6—C555.50 (19)
C19—C9—C10—C12−8.2 (2)C2—C3—C4—C5−56.8 (2)
C19—C24—C23—C22−1.1 (2)C21—C22—C25B—F3B141.0 (15)
C19—C20—C21—C22−0.5 (2)C21—C22—C25B—F1B−103.9 (8)
C8—O2—C11—O3175.07 (13)C21—C22—C25B—F2B10.3 (12)
C8—O2—C11—C10−4.67 (14)C21—C22—C25A—F1A−114.8 (3)
C8—C9—C10—C11−0.15 (15)C21—C22—C25A—F2A6.1 (4)
C8—C9—C10—C12178.09 (13)C21—C22—C25A—F3A127.9 (4)
C9—C19—C24—C23177.42 (13)C18—C12—C10—C9−41.9 (2)
C9—C19—C20—C21−176.65 (14)C18—C12—C10—C11136.14 (15)
C24—C19—C9—C8−41.76 (19)C18—C12—C13—C141.4 (2)
C24—C19—C9—C10145.21 (15)C18—C17—C15—O5−178.43 (15)
C24—C19—C20—C210.1 (2)C18—C17—C15—C140.3 (3)
C24—C23—C22—C210.7 (3)C6—C1—C2—C3−56.43 (18)
C24—C23—C22—C25B164.0 (5)C6—C5—C4—C355.1 (2)
C24—C23—C22—C25A−173.4 (2)C25B—C22—C21—C20−163.6 (5)
C11—O2—C8—C7−111.87 (12)C16—O4—C17—C1511.93 (18)
C11—O2—C8—C94.42 (14)C16—O4—C17—C18−170.00 (17)
C20—C19—C9—C8134.97 (14)C16—O5—C15—C17−11.56 (18)
C20—C19—C9—C10−38.1 (2)C16—O5—C15—C14169.81 (18)
C20—C19—C24—C230.6 (2)C25A—C22—C21—C20173.8 (2)
C10—C12—C13—C14−178.21 (14)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.821 (18)2.061 (18)2.8699 (16)168.4 (16)
Symmetry code: (i) −x+3/2, y−1/2, z.
Hydrogen-bond geometry (Å, º) for (I) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.845 (17)2.209 (17)3.0098 (14)158.2 (15)
Symmetry code: (i) x, −y+1/2, z−1/2.
Hydrogen-bond geometry (Å, º) for (II) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.821 (18)2.061 (18)2.8699 (16)168.4 (16)
Symmetry code: (i) −x+3/2, y−1/2, z.

Experimental details

(I)(II)
Crystal data
Chemical formulaC22H19F4NO4C25H22F3NO5
Mr437.38473.43
Crystal system, space groupMonoclinic, P21/cOrthorhombic, Pbca
Temperature (K)100100
a, b, c (Å)8.0173 (8), 24.900 (2), 10.2186 (9)19.2990 (7), 9.5345 (3), 24.2188 (7)
α, β, γ (°)90, 96.738 (2), 9090, 90, 90
V (Å3)2025.9 (3)4456.4 (2)
Z48
Radiation typeMo KαMo Kα
µ (mm−1)0.120.12
Crystal size (mm)0.3 × 0.2 × 0.20.35 × 0.25 × 0.2
Data collection
DiffractometerBruker APEXII CCD
diffractometer		Bruker APEXII CCD
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2009)		Multi-scan
(SADABS; Bruker, 2012)
Tmin, Tmax0.589, 0.7460.609, 0.745
No. of measured, independent and
observed [I > 2σ(I)] reflections		16716, 4139, 3698 36729, 3939, 3383
Rint0.0220.033
(sin θ/λ)max (Å−1)0.6250.595
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.034, 0.084, 1.03 0.035, 0.086, 1.05
No. of reflections41393939
No. of parameters287324
No. of restraints030
H-atom treatmentH atoms treated by a mixture of independent and constrained refinementH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)0.31, −0.320.27, −0.36

Computer programs: APEX2 (Bruker, 2009), APEX2 (Bruker, 2012), SAINT (Bruker, 2009), SAINT (Bruker, 2012), SHELXS97 (Sheldrick, 2008), OLEX.SOLVE (Bourhis et al., 2015), SHELXL2014 (Sheldrick, 2015), OLEX2 (Dolomanov et al., 2009).

 

Acknowledgements

The authors acknowledge financial support from the National Institute of Health (grant P41GM086190 to CH) and CONACyT/UA (doctoral fellowship 215981/311412 for GMA).

References

First citationBeck, B., Magnin-Lachaux, M., Herdtweck, E. & Dömling, A. (2001). Org. Lett. 3, 2875–2878.  Google Scholar
 First citationBossio, R., Marcaccini, S. & Pepino, R. (1994). Liebigs Ann. Chem. 1994, 527–528.  Google Scholar
 First citationBossio, R., Marcaccini, S., Pepino, R. & Torroba, T. (1993). Synthesis, pp. 783–785.  Google Scholar
 First citationBourhis, L. J., Dolomanov, O. V., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2015). Acta Cryst. A71, 59–75.  Web of Science CrossRef IUCr Journals Google Scholar
 First citationBruker (2009). APEX2, SAINT, and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
 First citationBruker (2012). APEX2, SAINT, and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
 First citationDe Souza, M. V. N. (2005). Mini-Rev. Org. Chem. 2, 139–145.  Google Scholar
 First citationDolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationGroom, C. R. & Allen, F. H. (2014). Angew. Chem. Int. Ed. 53, 662–671.  Web of Science CrossRef CAS Google Scholar
 First citationJung, J. H., Pummangura, S., Chaichantipyuth, C., Patarapanich, C., Fanwick, P. E., Chang, C.-J. & Mclaughlin, J. L. (1990). Tetrahedron, 46, 5043–5054.  Google Scholar
 First citationMarcaccini, S., Pepino, R., Marcos, C. F., Polo, C. & Torroba, T. (2000). J. Heterocycl. Chem. 37, 1501–1503.  Google Scholar
 First citationPrasit, P., et al. (1999). Bioorg. Med. Chem. Lett. 9, 1773–1778.  Google Scholar
 First citationRossbach, J., Harms, K. & Koert, U. (2014). Eur. J. Org. Chem. pp. 993–1006.  Google Scholar
 First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationSheldrick, G. M. (2015). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
 First citationSikorska, J., Parker-Nance, S., Davies-Coleman, M., Vining, O. B., Sikora, A. E. & McPhail, K. L. J. (2012). J. Nat. Prod. 75, 1824–1827  Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 71| Part 2| February 2015| Pages 199-202
doi:10.1107/S2056989015000936
Follow Acta Cryst. E
Sign up for e-alerts
E-alerts
Follow Acta Cryst. on Twitter
Twitter
Follow us on facebook
Facebook
Sign up for RSS feeds
RSS