6-(4-Fluoro­phen­yl)-8-phenyl-2,3-dihydro-4H-imidazo[5,1-b][1,3]thiazin-4-one: an unusual [6–5] fused-ring system

Gallagher, J.F.; Le Bas, M.-D.H.; Coleman, C.M.; O'Shea, D.F.

doi:10.1107/S0108270107002375

organic compounds

STRUCTURAL
CHEMISTRY

ISSN: 2053-2296

Volume 63| Part 3| March 2007| Pages o160-o162

doi:10.1107/S0108270107002375

6-(4-Fluorophenyl)-8-phenyl-2,3-dihydro-4H-imidazo[5,1-b][1,3]thiazin-4-one: an unusual [6–5] fused-ring system

John F. Gallagher,^a ^* Marie-Delphine H. Le Bas,^b Claire M. Coleman ^b and Donal F. O'Shea ^b ^*

^aSchool of Chemical Sciences, Dublin City University, Dublin 9, Ireland, and ^bCentre for Synthesis and Chemical Biology, School of Chemistry and Chemical Biology, University College Dublin, Dublin 4, Ireland
^*Correspondence e-mail: john.gallagher@dcu.ie, donal.f.oshea@ucd.ie

(Received 1 December 2006; accepted 16 January 2007; online 10 February 2007)

The title compound, C₁₈H₁₃FN₂OS, is the first structural example of a [6–5] fused ring incorporating the 2,3-dihydro-4H-imidazo[5,1-b][1,3]thiazin-4-one molecular scaffold. The six-membered 2,3-dihydro-1,3-thiazin-4-one ring adopts an envelope conformation, with the S—CH₂ C atom displaced by 0.761 (2) Å from the five-atom plane (all within 0.05 Å of the mean plane). The imidazole ring is planar. The phenyl ring is twisted from coplanarity with the imidazole ring by 23.84 (5)° and the 4-fluorophenyl ring is twisted by 53.36 (6)°, due to a close C(aryl)—H⋯O=C contact with the thiazin-4-one carbonyl O atom. The primary intermolecular interaction involves a CH₂ group with the F atom [C⋯F = 3.256 (2) Å and C—H⋯F = 137°].

Comment

Heterocyclic compounds have been a traditional focal point for the development of new anticancer agents, with combinatorial (high-throughput) approaches to new ring systems being of current interest. In our research to develop new routes to diversely substituted drug-like heterocyclic scaffolds, classes of [5–5] [imidazo[5,1-b]thiazol-3-ones, (II)] and [6–5] [imidazo[5,1-b]thiazin-4-ones, (I)] fused-ring systems have been targeted (Le Bas et al., 2005 ; Le Bas & O'Shea, 2005 ; O'Shea et al., 2006 ). The [5–5] imidazo[2,1-b]thiazoles have shown promise as anticancer therapeutics (Andreani et al., 2000 ). However, the isomeric imidazo[5,1-b]thiazole systems have only recently been investigated and a crystal structure reported [(IIa); Le Bas et al., 2005]. We report here the first structural example of a [6–5] imidazo[5,1b]thiazin-4-one fused-ring system, viz. the title compound, (Ia).

imidazole ring, and the [5–5] fused-ring relatives, (II)

. In (Ia)

, geometric data for the diarylimidazole ring differ from the average values for imidazoles (Orpen et al., 1994

). The C1=C3 and C2=N2 bond lengths of 1.365 (2) (longer) and 1.3023 (19) Å (shorter) differ, though not significantly, from the expected values of 1.36 and 1.313 Å. However, the three C—N bond lengths for C1/C2—N1 and C3—N2 are ca 0.03 Å longer [1.4065 (18)/1.3986 (18) and 1.3943 (19) Å, respectively] than the corresponding average values in imidazoles (1.370/1.349 and 1.376 Å, respectively) (Orpen et al., 1994

), reflecting the effect of the extra ring attached at C1—N1. The imidazole ring is planar, with all five atoms within 0.002 (1) Å of the C₃N₂ mean plane. The phenyl ring is twisted from co-planarity with the imidazole ring by 23.84 (5)°, while the 4-fluorophenyl ring is twisted by 53.36 (6)° away from the central ring due to a close contact with the thiazin-4-one carbonyl atom O1 and an intermolecular interaction with a neighbouring π-arene, C22—H22⋯C24ⁱ [symmetry code: (i) 1 − x, $[{1\over 2}]$ + y, $[{1\over 2}]$ − z; Table 2

Reactivity studies reveal distinct differences between the [5–5] imidazo[5,1-b]thiazol-3-ones, (II), and [6–5] imidazo[5,1-b]thiazin-4-ones, (Ia)–(Ic). Firstly, ring opening by nucleophilic attack at the C13=O1 amide carbonyl group occurs relatively quickly (under mild conditions) for the [5–5] fused rings, (II), but only under more testing conditions for the [6–5] derivatives, (I). Secondly, H/D exchange occurs at the methylene H atoms in (II) at 323 K under facile conditions, but not for (I) under similar conditions (Le Bas et al., 2005). In order to rationalize these reactivity differences, the six-membered thiazin-4-one ring in (Ia) is compared with the five-membered thiazol-3-one ring in (II). The mode of amide bond reactivity of (Ia) is comparable with that observed for the hydrolysis and acyl transfer reactions of N-acetylimidazoles. This is attributed to the N-atom lone pair being part of the aromatic sextet, resulting in ineffective amide stabilization (Oakenfull & Jencks, 1971 ; Oakenfull et al., 1971 ). This is further substantiated by the IR carbonyl stretch peak being observed at 1743 cm⁻¹ for (Ia), which is considerably higher than expected for a typical amide (1630–1670 cm⁻¹; Williams & Fleming, 1989 ) or six-membered lactam (1660–1690 cm⁻¹).

The main difference is the nature of the thiazol-3-one and thiazin-4-one rings, with ring strain evident in the former. In (II) (Le Bas et al., 2005), analysis of two related systems, viz. (IIa)/(IIb), at the bridgehead atom N1 shows that all three C—N bonds range from 1.391 (2) to 1.409 (2) Å in (IIa) and from 1.388 (3) to 1.407 (3) Å in (IIb), whereas in (Ia) a range of 1.3986 (18)–1.4243 (19) Å reveals a distinct difference, with C13—N1 longer by 0.02 Å. In (Ia), the C1—N1—C2 angle is 105.7 (1)°, and C1—N1—C13 and C2—N1—C13 are similar [126.40 (12) and 126.84 (12)°, respectively], in contrast with the corresponding angles in (IIa)/(IIb) [106 and 115/138°, respectively], as C2—N1—C13 opens up by 11° in (IIa)/(IIb) compared with the value in (Ia). The N1—C13=O1 angles differ by 6°, with a value of 120.32 (14)° in (Ia) versus 126.0 (2)/126.7 (2)° in (IIa)/(IIb). Pyramidalization at atom N1 is negligible in both (Ia) and (IIa)/(IIb), as all three angles sum to 360°. Reactivity could be attributed to the more open and accessible N1—C13 bond, and greater ring strain facilitates increased susceptibility to nucleophilic ring opening in (IIa)/(IIb). The H/D exchange at the CH₂ group in (II) can be explained by the formation of a 10-π aromatic enol intermediate which facilitates the exchange mechanism, and this is not possible for (I) (see scheme below).

An edge-on view of the [6–5] fused ring in (Ia) down the S1—C12 axis is depicted in Fig. 2, showing the four-atom plane [S1/C1/C13/C12, atoms all within 0.005 (1) Å of the mean plane]. The envelope conformation of the C₄NS ring has atom C11 at the flap position displaced by 0.738 (2) Å from the four-atom plane in the same direction as atom N1, which is displaced by 0.095 (2) Å and oriented in the same direction. This envelope description is adequate, however, albeit with a small distortion towards a screw-boat; ring puckering parameters (Cremer & Pople, 1975 ) are Q = 0.560 (2) Å, θ = 120.5 (2)° and φ = 122.85 (18)°.

The primary intermolecular interaction involves a methylene CH₂ group with a symmetry-related F atom, with C11⋯F1ⁱ = 3.256 (2) Å and C11—H11⋯F1ⁱ = 137° [symmetry code: (i) 1 − x, y + $[{1\over 2}]$ , −z + $[{1\over 2}]$ ] (Fig. 3), in tandem with a C22⋯C24ⁱ contact (Table 2), generating a zigzag chain along the (010) direction. Given the paucity of structural data for this and related rings, we are now developing synthetic routes to new [5–5] and [5–6] fused rings with a view to comparing structural data with reactivity in order to gain a more complete insight into the chemical reactivity of these systems.

Figure 1
A view of (Ia)

, showing the atomic numbering scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.

Figure 2
An edge-on view of the [6–5] fused-ring system in (Ia)

, highlighting the envelope conformation.

Figure 3
A packing diagram (with unit cell) of the hydrogen-bonding and contact geometry in the zigzag chain along (010) in (Ia)

. Only two H atoms, H11A and H22, involved in these interactions and contacts have been included for clarity. [Symmetry codes: (i) 1 − x, y + $[{1\over 2}]$ , −z + $[{1\over 2}]$ ; (ii) x, 1 + y, z; (iii) 1 − x, y − $[{1\over 2}]$ , −z + $[{1\over 2}]$ .]

Experimental

Brief details of the synthesis of (Ia) have been reported previously (Le Bas et al., 2005). The compound was recrystallized from ethanol as a pale-yellow solid in 72% yield (m.p. 495–497 K). IR (KBr disc, ν, cm⁻¹): 1743, 1623; ¹H NMR (CDCl₃): δ 7.87 (d, J = 7.0 Hz, 2H), 7.60–7.64 (m, 2H), 7.41–7.44 (m, 2H), 7.31–7.34 (m, 1H), 7.05–7.10 (m, 2H), 3.27–3.15 (m, 4H); ¹⁹F NMR (CDCl₃): δ −111; ¹³C NMR (CDCl₃): δ 166.4, 163.6 (d, J_CF = 250.0 Hz), 149.8, 138.4, 132.6, 131.6 (d, J_CF = 8.6 Hz), 128.8, 128.7, 127.9, 127.1, 119.8, 115.2 (d, J_CF = 22.4 Hz), 37.3, 26.0. ES⁺–MS: m/z 325 (M + H)⁺; HRMS found: 323.0641 (M − H)⁻; C₁₈H₁₂FN₂OS requires: 323.0654. Analysis calculated for C₁₈H₁₃FN₂OS: C 66.65, H 4.04, N 8.64, S 9.89%; found: C 66.42, H 4.01, N 8.54, S 10.07%.

Crystal data

C₁₈H₁₃FN₂OS
M_r = 324.36
Monoclinic, P 2₁ /c
a = 11.5195 (13) Å
b = 8.6516 (7) Å
c = 15.9173 (11) Å
β = 109.865 (5)°
V = 1492.0 (2) Å³
Z = 4
D_x = 1.444 Mg m⁻³
Mo Kα radiation
μ = 0.23 mm⁻¹
T = 294 (1) K
Block, colourless
0.45 × 0.45 × 0.35 mm

Data collection

Bruker P4 diffractometer
ω scans
4084 measured reflections
2938 independent reflections
2501 reflections with I > 2σ(I)
R_int = 0.017
θ_max = 26.1°
4 standard reflections every 296 reflections intensity decay: 1%

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.035
wR(F²) = 0.093
S = 1.04
2938 reflections
208 parameters
H-atom parameters constrained
w = 1/[σ²(F_o²) + (0.0448P)² + 0.385P] where P = (F_o² + 2F_c²)/3
(Δ/σ)_max = 0.001
Δρ_max = 0.29 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Table 1
Selected geometric parameters (Å, °)

S1—C1	1.7392 (15)
S1—C11	1.7986 (17)
C11—C12	1.512 (2)
C12—C13	1.498 (2)
N1—C1	1.4065 (18)
N1—C2	1.3986 (18)
N1—C13	1.4243 (19)
O1—C13	1.1976 (19)
C1—C3	1.365 (2)
N2—C2	1.3023 (19)
N2—C3	1.3943 (19)

S1—C1—N1	122.92 (11)
S1—C1—C3	130.76 (12)
N1—C1—C3	106.30 (12)
C1—N1—C2	105.70 (11)
C1—N1—C13	126.40 (12)
C2—N1—C13	126.84 (12)
C1—S1—C11	98.08 (7)
S1—C11—C12	111.10 (13)
C11—C12—C13	115.87 (14)
O1—C13—N1	120.32 (14)
O1—C13—C12	123.08 (15)
N1—C13—C12	116.59 (13)

N1—C1—S1—C11	20.39 (14)
C1—S1—C11—C12	−52.19 (13)
S1—C11—C12—C13	61.22 (18)
C11—C12—C13—N1	−27.8 (2)
C1—N1—C13—C12	−10.0 (2)
S1—C1—N1—C13	9.9 (2)
N2—C2—C21—C26	−53.1 (2)
N2—C3—C31—C32	−22.5 (2)

Table 2
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C11—H11A⋯F1ⁱ	0.97	2.48	3.256 (2)	137
C22—H22⋯C24ⁱ	0.93	2.85	3.753 (2)	164
C32—H32⋯N2	0.93	2.58	2.896 (2)	100
C36—H36⋯S1	0.93	2.67	3.3078 (18)	126
Symmetry code: (i) $[-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

In (Ia), all H atoms bound to carbon were treated as riding atoms, using SHELXL97 (Sheldrick, 1997 ) defaults for C—H bond lengths (range 0.93–0.97 Å), and with U_iso(H) = 1.5U_eq(C) for methylene H atoms or 1.2U_eq(C) for aromatic H atoms.

Data collection: XSCANS (Siemens, 1994 ); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997) and SORTX (McArdle, 1995 ); molecular graphics: PLATON (Spek, 2003 ); software used to prepare material for publication: SHELXL97 and PREP8 (Ferguson, 1998 ).

Supporting information

Crystal structure: contains datablocks global, Ia. DOI: 10.1107/S0108270107002375/hj3028sup1.cif

Structure factors: contains datablock Ia. DOI: 10.1107/S0108270107002375/hj3028Iasup2.hkl

Comment top

Heterocyclic compounds have been a traditional focal point for the development of new anticancer agents, with combinatorial (high-throughput) approaches to new ring systems being of current interest. In our research to develop new routes to diversely substituted drug-like heterocyclic scaffolds, classes of [5–5] [imidazo[5,1-b]thiazol-3-ones, (II)] and [6–5] [imidazo[5,1-b]thiazin-4-ones, (I)] fused-ring systems have been targeted (Le Bas et al., 2005; Le Bas & O'Shea, 2005; O'Shea et al., 2006). The [5–5] imidazo[2,1-b]thiazoles have shown promise as anticancer therapeutics (Andreani et al., 2000). However, the isomeric [5,1-b] systems have only recently been investigated and a crystal structure reported [(IIa); Le Bas et al., 2005]. Here, we report the first structural example of a [6–5] imidazo[5,1b]thiazin-4-one fused-ring system, the title compound, (Ia).

The molecular structure of (Ia) is depicted in Fig. 1, with the atomic numbering scheme, and selected bond lengths and angles are given in Table 1. Geometric data can be compared individually with different fused-ring systems. However, given that the [6–5] fused-ring in (Ia) is thus far unique, our focus is on comparisons with both the key ring systems, i.e. the imidazole ring, and the [5–5] fused-ring relatives, (II). In (Ia), geometric data for the bis-aryl(imidazo) rings differ from the average values for imidazoles (Orpen et al., 1994). The C1═C3 and C2═N2 bond lengths of 1.365 (2) Å (longer) and 1.3023 (19) Å (shorter) differ, though not significantly, from the expected values of 1.36 and 1.313 Å. However, the three C—N bond lengths for C1/C2—N1 and C3—N2 are ca 0.03 Å longer [1.4065 (18)/1.3986 (18) and 1.3943 (19) Å, respectively] than the corresponding average values in imidazoles [1.370/1.349 and 1.376 Å, respectively] (Orpen et al., 1994), reflecting the effect of the extra ring attached at C1/N1. The imidazole ring is planar, with all five atoms within 0.002 (1) Å of the C₃N₂ mean plane. The phenyl ring is twisted from co-planarity with the imidazole ring by 23.84 (5)°, while the para-FC₆H₄ ring is twisted by 53.36 (6)° away from the central ring due to a close contact with the thiazin-4-one carbonyl atom O1 and an intermolecular interaction with a neighbouring π-arene, C22—H22···C24ⁱ [symmetry code: (i) 1 - x, 1/2 + y, 1/2 - z; Table 2].

Reactivity studies reveal distinct differences between the [5–5] imidazo[5,1-b]thiazol-3-ones, (II), and [6–5] imidazo[5,1-b]thiazin-4-ones, (Ia)–(Ic). Firstly, ring opening by nucleophilic attack at the amide carbonyl C13═O1 occurs relatively quickly (under mild conditions) for the [5–5] fused rings, (II), but only under more testing conditions for the [6–5] derivatives, (I). Secondly, H/D exchange occurs at the methylene H atoms in (II) at 323 K under facile conditions, but not for (I) under similar conditions (Le Bas et al., 2005). In order to rationalize these reactivity differences, the six-membered thiazin-4-one ring in (Ia) is compared with the five-membered thiazol-3-one ring in (II). The amide bond reactivity of (Ia) is comparable with that observed for the hydrolysis and acyl transfer reactions of N-acetylimidazoles. This is attributed to the N lone pair being part of the aromatic sextet, resulting in ineffective amide stabilization (Oakenfull & Jencks, 1971; Oakenfull et al., 1971). This is further substantiated by the IR carbonyl stretch peak being observed at 1743 cm^-1 for (Ia), which is considerably higher than expected for a typical amide (1630–1670 cm^-1; Reference?) or six-membered lactam (1660–1690 cm^-1; Reference?).

The main difference is the nature of the thiazol-3-one and thiazin-4-one rings, with ring strain evident in the former. In (II) (Le Bas et al., 2005), analysis of two related systems, (IIa)/(IIb), at the bridgehead atom N1 shows that all three C—N bonds range from 1.391 (2) to 1.409 (2) Å in (IIa) and from 1.388 (3) to 1.407 (3) Å in (IIb), whereas in (Ia) a range of 1.3986 (18) to 1.4243 (19) Å reveals a distinct difference, with C13—N1 longer by 0.02 Å. In (Ia), the C1—N1—C2 angle is 105.7 (1)°, and C1—N1—C13 and C2—N1—C13 are similar [126.40 (12) and 126.84 (12)°, respectively], in contrast with the corresponding angles in (IIa)/(IIb) [106° and 115/138°, respectively], as C2—N1—C13 opens up by 11° in (IIa)/(IIb) compared with the value in (Ia). The N1—C13═O1 angles differ by 6°, with a value of 120.32 (14)° in (Ia) versus 126.0 (2)/126.7 (2)° in (IIa)/(IIb). Pyramidalization at atom N1 is negligible in both (Ia) and (IIa)/(IIb), as all three angles sum to 360°. Reactivity could be attributed to the more open and accessible N1—C13 bond, and greater ring strain facilitates increased susceptibility to nucleophilic ring opening in (IIa)/(IIb). The H/D exchange at the CH₂ group in (II) can be explained by the formation of a 10-π aromatic enol intermediate which facilitates the exchange mechanism, and this is not possible for (I) (see scheme).

An edge-on view of the [6–5] fused ring in (Ia) is depicted in Fig. 2 with the four-atom plane [S1/C1/C13/C12, atoms all within 0.005 (1) Å of the mean plane] and down the S1—C12 axis. The envelope conformation of the C₄NS ring has atom C11 at the flap position and displaced by 0.738 (2) Å from the four-atom plane and in the same direction as atom N1, which is displaced by 0.095 (2) Å and oriented in the same direction. This envelope description is adequate, however, although with a small distortion towards a screw-boat; ring puckering parameters (Cremer & Pople, 1975) are Q = 0.560 (2) Å, θ = 120.5 (2)° and ϕ = 122.85 (18)°.

The primary intermolecular interaction involves a methylene CH₂ group with a symmetry-related F atom, with C11···F1ⁱ = 3.256 (2) Å and C11—H11.·F1ⁱ = 137° [symmetry code: (i) 1 - x, y + 1/2, -z + 1/2] (Fig. 3), in tandem with a C22.·C24ⁱ contact (Table 2), generating a zigzag chain along the (010) direction. Given the paucity of structural data for this and related rings, we are now developing synthetic routes to new [5–5] and [5–6] fused rings with a view to comparing structural data with reactivity in order to gain a more complete insight into the chemical reactivity of these systems.

Related literature top

For related literature, see: Andreani et al. (2000); Cremer & Pople (1975); Le Bas & O'Shea (2005); Le Bas, McKinley, Hogan & O'Shea (2005); O'Shea et al. (2006); Oakenfull & Jencks (1971); Oakenfull, Salvesen & Jencks (1971); Orpen et al. (1994); Sheldrick (1997).

Experimental top

Brief details of the synthesis of (Ia) have previously been reported by us (Le Bas et al., 2005). The compound was recrystallized from ethanol as a pale-yellow solid in 72% yield (m.p. 495–497 K). Spectroscopic analysis: IR (KBr disc, ν, cm^-1): 1743, 1623; ¹H NMR (CDCl₃, δ, p.p.m.): 7.87 (d, J = 7.0 Hz, 2H), 7.60–7.64 (m, 2H), 7.41–7.44 (m, 2H), 7.31–7.34 (m, 1H), 7.05–7.10 (m, 2H), 3.27–3.15 (m, 4H); ¹⁹F NMR (CDCl₃, δ, p.p.m.): -111; ¹³C NMR (CDCl₃, δ, p.p.m.): 166.4, 163.6 (d, J_CF = 250.0 Hz), 149.8, 138.4, 132.6, 131.6 (d, J_CF = 8.6 Hz), 128.8, 128.7, 127.9, 127.1, 119.8, 115.2 (d, J_CF = 22.4 Hz), 37.3, 26.0. ES⁺—MS: m/z 325 (M+H)⁺; HRMS found: 323.0641 (M-H)^-; C₁₈H₁₂FN₂OS requires: 323.0654. Analysis, calculated for C₁₈H₁₃FN₂OS: C 66.65, H 4.04, N 8.64, S 9.89%; found: C 66.42, H 4.01, N 8.54, S 10.07%.

Computing details top

Data collection: XSCANS (Siemens, 1994); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 and PREP8 (Ferguson, 1998).

Figures top

	Fig. 1. A view of (Ia), with the atomic numbering scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. An edge-on view of the [6–5] fused-ring system in (Ia), highlighting the envelope conformation.
	Fig. 3. A packing diagram (with unit cell) of the hydrogen bonding and contact geometry in the zigzag chain along (010) in (Ia). Only two H atoms, H11A and H22, involved in these interactions and contacts have been included for clarity. [Symmetry codes (i) 1 - x, y + 1/2, -z + 1/2; (ii) x, 1 + y, z; (iii) 1 - x, y - 1/2, -z + 1/2.]

6-(4-Fluorophenyl)-8-phenyl-2,3-dihydro-4H-imidazo[5,1-b][1,3]thiazin-4-one top

Crystal data top

C₁₈H₁₃FN₂OS	F(000) = 672
M_r = 324.36	D_x = 1.444 Mg m⁻³
Monoclinic, P2₁/c	Melting point: 496 K
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71073 Å
a = 11.5195 (13) Å	Cell parameters from 79 reflections
b = 8.6516 (7) Å	θ = 5.8–19.2°
c = 15.9173 (11) Å	µ = 0.23 mm⁻¹
β = 109.865 (5)°	T = 294 K
V = 1492.0 (2) Å³	Block, colourless
Z = 4	0.45 × 0.45 × 0.35 mm

Data collection top

Bruker P4 diffractometer	R_int = 0.017
Radiation source: X-ray tube	θ_max = 26.1°, θ_min = 1.9°
Graphite monochromator	h = −14→1
ω scans	k = −1→10
4084 measured reflections	l = −18→19
2938 independent reflections	4 standard reflections every 296 reflections
2501 reflections with I > 2σ(I)	intensity decay: 1%

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.035	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.093	H-atom parameters constrained
S = 1.04	w = 1/[σ²(F_o²) + (0.0448P)² + 0.385P] where P = (F_o² + 2F_c²)/3
2938 reflections	(Δ/σ)_max = 0.001
208 parameters	Δρ_max = 0.29 e Å⁻³
0 restraints	Δρ_min = −0.16 e Å⁻³

Crystal data top

C₁₈H₁₃FN₂OS	V = 1492.0 (2) Å³
M_r = 324.36	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 11.5195 (13) Å	µ = 0.23 mm⁻¹
b = 8.6516 (7) Å	T = 294 K
c = 15.9173 (11) Å	0.45 × 0.45 × 0.35 mm
β = 109.865 (5)°

Data collection top

Bruker P4 diffractometer	R_int = 0.017
4084 measured reflections	4 standard reflections every 296 reflections
2938 independent reflections	intensity decay: 1%
2501 reflections with I > 2σ(I)

Refinement top

R[F² > 2σ(F²)] = 0.035	0 restraints
wR(F²) = 0.093	H-atom parameters constrained
S = 1.04	Δρ_max = 0.29 e Å⁻³
2938 reflections	Δρ_min = −0.16 e Å⁻³
208 parameters

Special details top

Geometry. Mean plane data ex-SHELXL97 for molecule (I) ############################################

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.95656 (13)	0.28746 (18)	0.29047 (10)	0.0388 (3)
N1	0.83290 (11)	0.23798 (15)	0.26081 (8)	0.0381 (3)
C2	0.80720 (13)	0.19936 (18)	0.33801 (10)	0.0379 (3)
N2	0.90323 (11)	0.22051 (15)	0.40947 (8)	0.0412 (3)
C3	0.99766 (13)	0.27604 (18)	0.38139 (10)	0.0390 (3)
S1	1.03241 (4)	0.34442 (6)	0.21794 (3)	0.05373 (15)
C11	0.89858 (15)	0.3857 (2)	0.12204 (11)	0.0499 (4)
C12	0.81006 (16)	0.2506 (2)	0.09991 (11)	0.0508 (4)
C13	0.75842 (14)	0.20520 (19)	0.17095 (10)	0.0435 (4)
O1	0.66082 (11)	0.14194 (18)	0.15508 (8)	0.0663 (4)
F1	0.35036 (10)	0.04056 (14)	0.36147 (9)	0.0763 (4)
C21	0.68498 (13)	0.15453 (17)	0.34110 (9)	0.0371 (3)
C22	0.58199 (14)	0.24579 (19)	0.30130 (10)	0.0436 (4)
C23	0.46930 (15)	0.2098 (2)	0.30904 (11)	0.0482 (4)
C24	0.46229 (15)	0.0807 (2)	0.35643 (12)	0.0482 (4)
C25	0.56080 (16)	−0.0113 (2)	0.39737 (12)	0.0531 (4)
C26	0.67402 (15)	0.02637 (19)	0.38989 (11)	0.0462 (4)
C31	1.11685 (13)	0.32005 (17)	0.44758 (10)	0.0396 (3)
C32	1.12381 (15)	0.3586 (2)	0.53391 (11)	0.0470 (4)
C33	1.23423 (16)	0.4031 (2)	0.59667 (12)	0.0550 (4)
C34	1.34041 (16)	0.4106 (2)	0.57479 (13)	0.0559 (5)
C35	1.33527 (15)	0.3728 (2)	0.48963 (13)	0.0530 (4)
C36	1.22485 (14)	0.3272 (2)	0.42633 (12)	0.0469 (4)
H11A	0.8571	0.4764	0.1339	0.060*
H11B	0.9241	0.4082	0.0712	0.060*
H12A	0.7418	0.2756	0.0461	0.061*
H12B	0.8523	0.1619	0.0866	0.061*
H22	0.5889	0.3326	0.2689	0.052*
H23	0.4004	0.2715	0.2828	0.058*
H25	0.5526	−0.0977	0.4297	0.064*
H26	0.7428	−0.0347	0.4178	0.055*
H32	1.0531	0.3543	0.5495	0.056*
H33	1.2373	0.4282	0.6542	0.066*
H34	1.4147	0.4410	0.6173	0.067*
H35	1.4064	0.3780	0.4745	0.064*
H36	1.2226	0.3011	0.3691	0.056*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0325 (7)	0.0420 (8)	0.0431 (8)	−0.0004 (6)	0.0146 (6)	−0.0020 (6)
N1	0.0332 (6)	0.0455 (7)	0.0363 (6)	−0.0019 (5)	0.0128 (5)	−0.0026 (5)
C2	0.0356 (7)	0.0419 (8)	0.0373 (7)	−0.0008 (6)	0.0136 (6)	−0.0001 (6)
N2	0.0358 (6)	0.0481 (7)	0.0388 (6)	−0.0019 (6)	0.0117 (5)	0.0016 (6)
C3	0.0333 (7)	0.0419 (8)	0.0417 (8)	0.0017 (6)	0.0129 (6)	−0.0002 (6)
S1	0.0399 (2)	0.0782 (3)	0.0471 (2)	−0.0052 (2)	0.01998 (18)	0.0044 (2)
C11	0.0502 (9)	0.0585 (10)	0.0436 (8)	−0.0001 (8)	0.0193 (7)	0.0041 (8)
C12	0.0529 (9)	0.0632 (11)	0.0377 (8)	−0.0052 (8)	0.0170 (7)	−0.0051 (8)
C13	0.0402 (8)	0.0514 (9)	0.0393 (8)	−0.0008 (7)	0.0141 (6)	−0.0082 (7)
O1	0.0465 (7)	0.1063 (11)	0.0477 (7)	−0.0260 (7)	0.0180 (5)	−0.0247 (7)
F1	0.0541 (6)	0.0745 (8)	0.1170 (10)	−0.0151 (6)	0.0509 (7)	−0.0063 (7)
C21	0.0356 (7)	0.0412 (8)	0.0348 (7)	−0.0043 (6)	0.0124 (6)	−0.0044 (6)
C22	0.0427 (8)	0.0454 (9)	0.0438 (8)	0.0002 (7)	0.0161 (7)	0.0056 (7)
C23	0.0376 (8)	0.0546 (10)	0.0527 (9)	0.0042 (7)	0.0159 (7)	0.0001 (8)
C24	0.0413 (8)	0.0515 (9)	0.0593 (10)	−0.0106 (7)	0.0270 (8)	−0.0112 (8)
C25	0.0594 (10)	0.0438 (9)	0.0626 (11)	−0.0080 (8)	0.0292 (9)	0.0052 (8)
C26	0.0438 (8)	0.0435 (9)	0.0501 (9)	0.0007 (7)	0.0142 (7)	0.0044 (7)
C31	0.0337 (7)	0.0385 (8)	0.0437 (8)	0.0032 (6)	0.0092 (6)	0.0023 (6)
C32	0.0391 (8)	0.0541 (10)	0.0458 (8)	0.0032 (7)	0.0119 (7)	0.0006 (7)
C33	0.0487 (9)	0.0610 (11)	0.0471 (9)	0.0033 (8)	0.0057 (7)	−0.0063 (8)
C34	0.0396 (9)	0.0534 (10)	0.0616 (11)	−0.0001 (8)	0.0000 (8)	−0.0039 (8)
C35	0.0341 (8)	0.0533 (10)	0.0681 (11)	0.0019 (7)	0.0131 (8)	0.0043 (9)
C36	0.0376 (8)	0.0506 (9)	0.0516 (9)	0.0030 (7)	0.0138 (7)	0.0002 (7)

Geometric parameters (Å, º) top

S1—C1	1.7392 (15)	C31—C32	1.390 (2)
S1—C11	1.7986 (17)	C31—C36	1.397 (2)
C11—C12	1.512 (2)	C32—C33	1.379 (2)
C12—C13	1.498 (2)	C33—C34	1.382 (3)
N1—C1	1.4065 (18)	C34—C35	1.376 (3)
N1—C2	1.3986 (18)	C35—C36	1.385 (2)
N1—C13	1.4243 (19)	C22—H22	0.93
O1—C13	1.1976 (19)	C23—H23	0.93
C1—C3	1.365 (2)	C25—H25	0.93
N2—C2	1.3023 (19)	C26—H26	0.93
N2—C3	1.3943 (19)	C32—H32	0.93
C2—C21	1.4772 (19)	C33—H33	0.93
C3—C31	1.469 (2)	C34—H34	0.93
C21—C22	1.386 (2)	C11—H11A	0.97
C21—C26	1.384 (2)	C11—H11B	0.97
C22—C23	1.381 (2)	C12—H12A	0.97
C23—C24	1.366 (2)	C12—H12B	0.97
F1—C24	1.3636 (17)	C35—H35	0.93
C24—C25	1.358 (2)	C36—H36	0.93
C25—C26	1.388 (2)

S1—C1—N1	122.92 (11)	C32—C33—C34	120.54 (17)
S1—C1—C3	130.76 (12)	C33—C34—C35	119.43 (16)
N1—C1—C3	106.30 (12)	C34—C35—C36	120.39 (16)
C1—N1—C2	105.70 (11)	C31—C36—C35	120.66 (16)
C1—N1—C13	126.40 (12)	C23—C22—H22	119.5
C2—N1—C13	126.84 (12)	C21—C22—H22	119.5
N1—C2—N2	111.29 (12)	C24—C23—H23	121.1
N1—C2—C21	125.50 (13)	C22—C23—H23	121.1
N2—C2—C21	122.97 (13)	C24—C25—H25	120.7
N2—C3—C31	120.03 (13)	C26—C25—H25	120.7
C2—N2—C3	106.99 (12)	C21—C26—H26	119.9
C1—C3—N2	109.73 (13)	C25—C26—H26	119.9
C1—C3—C31	130.14 (14)	C33—C32—H32	119.6
C1—S1—C11	98.08 (7)	C31—C32—H32	119.6
S1—C11—C12	111.10 (13)	C32—C33—H33	119.7
C11—C12—C13	115.87 (14)	C34—C33—H33	119.7
O1—C13—N1	120.32 (14)	C35—C34—H34	120.3
O1—C13—C12	123.08 (15)	C33—C34—H34	120.3
N1—C13—C12	116.59 (13)	C34—C35—H35	119.8
C26—C21—C22	119.06 (14)	C36—C35—H35	119.8
C26—C21—C2	119.92 (14)	C12—C11—H11A	109.4
C22—C21—C2	120.84 (14)	S1—C11—H11A	109.4
C21—C22—C23	121.03 (15)	C12—C11—H11B	109.4
C22—C23—C24	117.88 (15)	S1—C11—H11B	109.4
F1—C24—C23	118.36 (16)	H11A—C11—H11B	108.0
F1—C24—C25	118.39 (16)	C13—C12—H12A	108.3
C23—C24—C25	123.24 (15)	C11—C12—H12A	108.3
C24—C25—C26	118.52 (16)	C13—C12—H12B	108.3
C21—C26—C25	120.26 (15)	C11—C12—H12B	108.3
C32—C31—C36	118.16 (15)	H12A—C12—H12B	107.4
C32—C31—C3	119.81 (14)	C35—C36—H36	119.7
C36—C31—C3	122.02 (14)	C31—C36—H36	119.7
C31—C32—C33	120.83 (15)

N1—C1—S1—C11	20.39 (14)	C2—N1—C13—C12	−176.47 (15)
C1—S1—C11—C12	−52.19 (13)	C11—C12—C13—O1	153.51 (18)
S1—C11—C12—C13	61.22 (18)	N1—C2—C21—C26	133.05 (16)
C11—C12—C13—N1	−27.8 (2)	N2—C2—C21—C22	121.96 (17)
C1—N1—C13—C12	−10.0 (2)	N1—C2—C21—C22	−51.9 (2)
S1—C1—N1—C13	9.9 (2)	C26—C21—C22—C23	−0.6 (2)
N1—C2—N2—C3	0.38 (17)	C2—C21—C22—C23	−175.68 (14)
C2—N2—C3—C1	−0.31 (18)	C21—C22—C23—C24	−0.6 (2)
N2—C2—C21—C26	−53.1 (2)	C22—C23—C24—C25	1.3 (3)
N2—C3—C31—C32	−22.5 (2)	C22—C23—C24—F1	−177.39 (15)
C3—C1—N1—C2	0.11 (16)	F1—C24—C25—C26	177.91 (15)
S1—C1—N1—C2	178.65 (11)	C23—C24—C25—C26	−0.8 (3)
C3—C1—N1—C13	−168.68 (14)	C22—C21—C26—C25	1.1 (2)
C1—N1—C2—N2	−0.31 (17)	C2—C21—C26—C25	176.26 (15)
C13—N1—C2—N2	168.41 (14)	C24—C25—C26—C21	−0.4 (3)
C1—N1—C2—C21	174.16 (14)	C1—C3—C31—C32	153.46 (17)
C13—N1—C2—C21	−17.1 (2)	C1—C3—C31—C36	−25.4 (3)
C21—C2—N2—C3	−174.25 (14)	N2—C3—C31—C36	158.59 (15)
N1—C1—C3—N2	0.11 (17)	C36—C31—C32—C33	0.2 (3)
S1—C1—C3—N2	−178.27 (12)	C3—C31—C32—C33	−178.75 (16)
N1—C1—C3—C31	−176.17 (15)	C31—C32—C33—C34	0.2 (3)
S1—C1—C3—C31	5.4 (3)	C32—C33—C34—C35	−0.2 (3)
C2—N2—C3—C31	176.42 (14)	C33—C34—C35—C36	−0.2 (3)
C3—C1—S1—C11	−161.45 (16)	C34—C35—C36—C31	0.5 (3)
C2—N1—C13—O1	2.3 (3)	C32—C31—C36—C35	−0.5 (2)
C1—N1—C13—O1	168.73 (16)	C3—C31—C36—C35	178.38 (15)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C11—H11A···F1ⁱ	0.97	2.48	3.256 (2)	137
C22—H22···C24ⁱ	0.93	2.85	3.753 (2)	164
C32—H32···N2	0.93	2.58	2.896 (2)	100
C36—H36···S1	0.93	2.67	3.3078 (18)	126

Symmetry code: (i) −x+1, y+1/2, −z+1/2.

Experimental details

Crystal data
Chemical formula	C₁₈H₁₃FN₂OS
M_r	324.36
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	294
a, b, c (Å)	11.5195 (13), 8.6516 (7), 15.9173 (11)
β (°)	109.865 (5)
V (Å³)	1492.0 (2)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.23
Crystal size (mm)	0.45 × 0.45 × 0.35

Data collection
Diffractometer	Bruker P4 diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	4084, 2938, 2501
R_int	0.017
(sin θ/λ)_max (Å⁻¹)	0.618

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.035, 0.093, 1.04
No. of reflections	2938
No. of parameters	208
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.29, −0.16

Computer programs: XSCANS (Siemens, 1994), XSCANS, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 2003), SHELXL97 and PREP8 (Ferguson, 1998).

Selected geometric parameters (Å, º) top

S1—C1	1.7392 (15)	N1—C13	1.4243 (19)
S1—C11	1.7986 (17)	O1—C13	1.1976 (19)
C11—C12	1.512 (2)	C1—C3	1.365 (2)
C12—C13	1.498 (2)	N2—C2	1.3023 (19)
N1—C1	1.4065 (18)	N2—C3	1.3943 (19)
N1—C2	1.3986 (18)

S1—C1—N1	122.92 (11)	C1—S1—C11	98.08 (7)
S1—C1—C3	130.76 (12)	S1—C11—C12	111.10 (13)
N1—C1—C3	106.30 (12)	C11—C12—C13	115.87 (14)
C1—N1—C2	105.70 (11)	O1—C13—N1	120.32 (14)
C1—N1—C13	126.40 (12)	O1—C13—C12	123.08 (15)
C2—N1—C13	126.84 (12)	N1—C13—C12	116.59 (13)

N1—C1—S1—C11	20.39 (14)	C1—N1—C13—C12	−10.0 (2)
C1—S1—C11—C12	−52.19 (13)	S1—C1—N1—C13	9.9 (2)
S1—C11—C12—C13	61.22 (18)	N2—C2—C21—C26	−53.1 (2)
C11—C12—C13—N1	−27.8 (2)	N2—C3—C31—C32	−22.5 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C11—H11A···F1ⁱ	0.97	2.48	3.256 (2)	137
C22—H22···C24ⁱ	0.93	2.85	3.753 (2)	164
C32—H32···N2	0.93	2.58	2.896 (2)	100
C36—H36···S1	0.93	2.67	3.3078 (18)	126

Symmetry code: (i) −x+1, y+1/2, −z+1/2.

Acknowledgements

JFG thanks Dublin City University for the purchase in 1998 of the Siemens P4 diffractometer and computer system. The synthetic research was funded by Enterprise Ireland and PRTLI-3 (Programme for Research in Third-Level Institutions) administered by the Higher Education Authority, Ireland.

References

Andreani, A., Leoni, A., Locatelli, A., Morigi, R., Rambaldi, M., Recanatini, M. & Garaliene, V. (2000). Bioorg. Med. Chem. 8, 2359–2366. Web of Science CrossRef PubMed CAS Google Scholar
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Volume 63| Part 3| March 2007| Pages o160-o162

doi:10.1107/S0108270107002375

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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

6-(4-Fluoro­phen­yl)-8-phenyl-2,3-di­hydro-4H-imidazo[5,1-b][1,3]thiazin-4-one: an unusual [6–5] fused-ring system

Comment

Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

6-(4-Fluorophenyl)-8-phenyl-2,3-dihydro-4H-imidazo[5,1-b][1,3]thiazin-4-one: an unusual [6–5] fused-ring system