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CHEMISTRY
ISSN: 2053-2296

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

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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)[link]] and [6–5] [imidazo[5,1-b]thia­zin-4-ones, (I)[link]] fused-ring systems have been targeted (Le Bas et al., 2005[Le Bas, M.-D. H., McKinley, N. F., Hogan, A.-M. L. & O'Shea, D. F. (2005). J. Combin. Chem. 7, 503-506.]; Le Bas & O'Shea, 2005[Le Bas, M.-D. H. & O'Shea, D. F. (2005). J. Combin. Chem. 7, 974-951.]; O'Shea et al., 2006[O'Shea, D. F., Le Bas, M.-D. H. & Mueller-Bunz, H. (2006). Unpublished results. University College Dublin, Ireland.]). The [5–5] imidazo[2,1-b]thia­zoles have shown promise as anti­cancer therapeutics (Andreani et al., 2000[Andreani, A., Leoni, A., Locatelli, A., Morigi, R., Rambaldi, M., Recanatini, M. & Garaliene, V. (2000). Bioorg. Med. Chem. 8, 2359-2366.]). However, the isomeric imidazo[5,1-b]thiazole systems have only recently been investigated and a crystal structure reported [(IIa)[link]; Le Bas et al., 2005[Le Bas, M.-D. H., McKinley, N. F., Hogan, A.-M. L. & O'Shea, D. F. (2005). J. Combin. Chem. 7, 503-506.]]. 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)[link].

The mol­ecular structure of (Ia) is depicted in Fig. 1[link], with the atomic numbering scheme, and selected bond lengths and angles are given in Table 1[link]. Geometric data can be compared individually with different fused-ring systems. However, given that the [6–5] fused-ring in (Ia)[link] is thus far unique, our focus is on comparisons with both the key ring systems, i.e. the

[Scheme 1]
imidazole ring, and the [5–5] fused-ring relatives, (II)[link]. In (Ia)[link], geometric data for the diarylimidazole ring differ from the average values for imidazoles (Orpen et al., 1994[Orpen, A. G., Brammer, L., Allen, F. H., Kennard, O., Watson, D. G. & Taylor, R. (1994). Structure Correlation, Vol. 2, Appendix A, edited by H.-B. Bürgi & J. D. Dunitz. Weinheim: VCH.]). 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[Orpen, A. G., Brammer, L., Allen, F. H., Kennard, O., Watson, D. G. & Taylor, R. (1994). Structure Correlation, Vol. 2, Appendix A, edited by H.-B. Bürgi & J. D. Dunitz. Weinheim: VCH.]), 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[link]].

Reactivity studies reveal distinct differences between the [5–5] imidazo[5,1-b]thia­zol-3-ones, (II)[link], and [6–5] imidazo[5,1-b]thia­zin-4-ones, (Ia)[link]–(Ic)[link]. 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)[link], but only under more testing conditions for the [6–5] derivatives, (I)[link]. Secondly, H/D exchange occurs at the methyl­ene H atoms in (II)[link] at 323 K under facile conditions, but not for (I)[link] under similar conditions (Le Bas et al., 2005[Le Bas, M.-D. H., McKinley, N. F., Hogan, A.-M. L. & O'Shea, D. F. (2005). J. Combin. Chem. 7, 503-506.]). In order to rationalize these reactivity differences, the six-membered thia­zin-4-one ring in (Ia)[link] is compared with the five-membered thia­zol-3-one ring in (II)[link]. The mode of amide bond reactivity of (Ia)[link] 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, D. G. & Jencks, W. P. (1971). J. Am. Chem. Soc. 93, 178-188.]; Oakenfull et al., 1971[Oakenfull, D. G., Salvesen, K. & Jencks, W. P. (1971). J. Am. Chem. Soc. 93, 188-194.]). This is further substanti­ated by the IR carbonyl stretch peak being observed at 1743 cm−1 for (Ia)[link], which is considerably higher than expected for a typical amide (1630–1670 cm−1; Williams & Fleming, 1989[Williams, D. H. & Fleming, I. (1989). Spectroscopic Methods in Organic Chemistry, 4th ed. London: McGraw-Hill.]) 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)[link] (Le Bas et al., 2005[Le Bas, M.-D. H., McKinley, N. F., Hogan, A.-M. L. & O'Shea, D. F. (2005). J. Combin. Chem. 7, 503-506.]), analysis of two related systems, viz. (IIa)[link]/(IIb)[link], at the bridgehead atom N1 shows that all three C—N bonds range from 1.391 (2) to 1.409 (2) Å in (IIa)[link] and from 1.388 (3) to 1.407 (3) Å in (IIb)[link], whereas in (Ia)[link] a range of 1.3986 (18)–1.4243 (19) Å reveals a distinct difference, with C13—N1 longer by 0.02 Å. In (Ia)[link], 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)[link]/(IIb)[link] [106 and 115/138°, respectively], as C2—N1—C13 opens up by 11° in (IIa)[link]/(IIb)[link] compared with the value in (Ia)[link]. The N1—C13=O1 angles differ by 6°, with a value of 120.32 (14)° in (Ia)[link] versus 126.0 (2)/126.7 (2)° in (IIa)[link]/(IIb)[link]. Pyramidalization at atom N1 is negligible in both (Ia)[link] and (IIa)[link]/(IIb)[link], 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)[link]/(IIb)[link]. The H/D exchange at the CH2 group in (II)[link] 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)[link] (see scheme[link] below).

[Scheme 2]

An edge-on view of the [6–5] fused ring in (Ia)[link] down the S1—C12 axis is depicted in Fig. 2[link], 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[Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358.]) 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[link]), in tandem with a C22⋯C24i contact (Table 2[link]), 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]
Figure 1
A view of (Ia)[link], 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]
Figure 2
An edge-on view of the [6–5] fused-ring system in (Ia)[link], highlighting the envelope conformation.
[Figure 3]
Figure 3
A packing diagram (with unit cell) of the hydrogen-bonding and contact geometry in the zigzag chain along (010) in (Ia)[link]. 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)[link] have been reported previously (Le Bas et al., 2005[Le Bas, M.-D. H., McKinley, N. F., Hogan, A.-M. L. & O'Shea, D. F. (2005). J. Combin. Chem. 7, 503-506.]). 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, JCF = 250.0 Hz), 149.8, 138.4, 132.6, 131.6 (d, JCF = 8.6 Hz), 128.8, 128.7, 127.9, 127.1, 119.8, 115.2 (d, JCF = 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

  • Mr = 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

  • Dx = 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)

  • Rint = 0.017

  • θmax = 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(Fo2) + (0.0448P)2 + 0.385P] where P = (Fo2 + 2Fc2)/3

  • (Δ/σ)max = 0.001

  • Δρmax = 0.29 e Å−3

  • Δρmin = −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 DA 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)[link], all H atoms bound to carbon were treated as riding atoms, using SHELXL97 (Sheldrick, 1997[Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Göttingen, Germany.]) defaults for C—H bond lengths (range 0.93–0.97 Å), and with Uiso(H) = 1.5Ueq(C) for methyl­ene H atoms or 1.2Ueq(C) for aromatic H atoms.

Data collection: XSCANS (Siemens, 1994[Siemens (1994). XSCANS. Version 2.1. Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.]); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997[Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Göttingen, Germany.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997[Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Göttingen, Germany.]) and SORTX (McArdle, 1995[McArdle, P. (1995). J. Appl. Cryst. 28, 65.]); molecular graphics: PLATON (Spek, 2003[Spek, A. L. (2003). J. Appl. Cryst. 36, 7-13.]); software used to prepare material for publication: SHELXL97 and PREP8 (Ferguson, 1998[Ferguson, G. (1998). PREP8. University of Guelph, Canada.]).

Supporting information


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 C1C3 and C2N2 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 C13O1 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—C13O1 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, JCF = 250.0 Hz), 149.8, 138.4, 132.6, 131.6 (d, JCF = 8.6 Hz), 128.8, 128.7, 127.9, 127.1, 119.8, 115.2 (d, JCF = 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%.

Refinement top

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

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
[Figure 1] 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.
[Figure 2] Fig. 2. An edge-on view of the [6–5] fused-ring system in (Ia), highlighting the envelope conformation.
[Figure 3] 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
C18H13FN2OSF(000) = 672
Mr = 324.36Dx = 1.444 Mg m3
Monoclinic, P21/cMelting point: 496 K
Hall symbol: -P 2ybcMo Kα radiation, λ = 0.71073 Å
a = 11.5195 (13) ÅCell parameters from 79 reflections
b = 8.6516 (7) Åθ = 5.8–19.2°
c = 15.9173 (11) ŵ = 0.23 mm1
β = 109.865 (5)°T = 294 K
V = 1492.0 (2) Å3Block, colourless
Z = 40.45 × 0.45 × 0.35 mm
Data collection top
Bruker P4
diffractometer
Rint = 0.017
Radiation source: X-ray tubeθmax = 26.1°, θmin = 1.9°
Graphite monochromatorh = 141
ω scansk = 110
4084 measured reflectionsl = 1819
2938 independent reflections4 standard reflections every 296 reflections
2501 reflections with I > 2σ(I) intensity decay: 1%
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)] = 0.035Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.093H-atom parameters constrained
S = 1.04 w = 1/[σ2(Fo2) + (0.0448P)2 + 0.385P]
where P = (Fo2 + 2Fc2)/3
2938 reflections(Δ/σ)max = 0.001
208 parametersΔρmax = 0.29 e Å3
0 restraintsΔρmin = 0.16 e Å3
Crystal data top
C18H13FN2OSV = 1492.0 (2) Å3
Mr = 324.36Z = 4
Monoclinic, P21/cMo Kα radiation
a = 11.5195 (13) ŵ = 0.23 mm1
b = 8.6516 (7) ÅT = 294 K
c = 15.9173 (11) Å0.45 × 0.45 × 0.35 mm
β = 109.865 (5)°
Data collection top
Bruker P4
diffractometer
Rint = 0.017
4084 measured reflections4 standard reflections every 296 reflections
2938 independent reflections intensity decay: 1%
2501 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.0350 restraints
wR(F2) = 0.093H-atom parameters constrained
S = 1.04Δρmax = 0.29 e Å3
2938 reflectionsΔρmin = 0.16 e Å3
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
xyzUiso*/Ueq
C10.95656 (13)0.28746 (18)0.29047 (10)0.0388 (3)
N10.83290 (11)0.23798 (15)0.26081 (8)0.0381 (3)
C20.80720 (13)0.19936 (18)0.33801 (10)0.0379 (3)
N20.90323 (11)0.22051 (15)0.40947 (8)0.0412 (3)
C30.99766 (13)0.27604 (18)0.38139 (10)0.0390 (3)
S11.03241 (4)0.34442 (6)0.21794 (3)0.05373 (15)
C110.89858 (15)0.3857 (2)0.12204 (11)0.0499 (4)
C120.81006 (16)0.2506 (2)0.09991 (11)0.0508 (4)
C130.75842 (14)0.20520 (19)0.17095 (10)0.0435 (4)
O10.66082 (11)0.14194 (18)0.15508 (8)0.0663 (4)
F10.35036 (10)0.04056 (14)0.36147 (9)0.0763 (4)
C210.68498 (13)0.15453 (17)0.34110 (9)0.0371 (3)
C220.58199 (14)0.24579 (19)0.30130 (10)0.0436 (4)
C230.46930 (15)0.2098 (2)0.30904 (11)0.0482 (4)
C240.46229 (15)0.0807 (2)0.35643 (12)0.0482 (4)
C250.56080 (16)0.0113 (2)0.39737 (12)0.0531 (4)
C260.67402 (15)0.02637 (19)0.38989 (11)0.0462 (4)
C311.11685 (13)0.32005 (17)0.44758 (10)0.0396 (3)
C321.12381 (15)0.3586 (2)0.53391 (11)0.0470 (4)
C331.23423 (16)0.4031 (2)0.59667 (12)0.0550 (4)
C341.34041 (16)0.4106 (2)0.57479 (13)0.0559 (5)
C351.33527 (15)0.3728 (2)0.48963 (13)0.0530 (4)
C361.22485 (14)0.3272 (2)0.42633 (12)0.0469 (4)
H11A0.85710.47640.13390.060*
H11B0.92410.40820.07120.060*
H12A0.74180.27560.04610.061*
H12B0.85230.16190.08660.061*
H220.58890.33260.26890.052*
H230.40040.27150.28280.058*
H250.55260.09770.42970.064*
H260.74280.03470.41780.055*
H321.05310.35430.54950.056*
H331.23730.42820.65420.066*
H341.41470.44100.61730.067*
H351.40640.37800.47450.064*
H361.22260.30110.36910.056*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0325 (7)0.0420 (8)0.0431 (8)0.0004 (6)0.0146 (6)0.0020 (6)
N10.0332 (6)0.0455 (7)0.0363 (6)0.0019 (5)0.0128 (5)0.0026 (5)
C20.0356 (7)0.0419 (8)0.0373 (7)0.0008 (6)0.0136 (6)0.0001 (6)
N20.0358 (6)0.0481 (7)0.0388 (6)0.0019 (6)0.0117 (5)0.0016 (6)
C30.0333 (7)0.0419 (8)0.0417 (8)0.0017 (6)0.0129 (6)0.0002 (6)
S10.0399 (2)0.0782 (3)0.0471 (2)0.0052 (2)0.01998 (18)0.0044 (2)
C110.0502 (9)0.0585 (10)0.0436 (8)0.0001 (8)0.0193 (7)0.0041 (8)
C120.0529 (9)0.0632 (11)0.0377 (8)0.0052 (8)0.0170 (7)0.0051 (8)
C130.0402 (8)0.0514 (9)0.0393 (8)0.0008 (7)0.0141 (6)0.0082 (7)
O10.0465 (7)0.1063 (11)0.0477 (7)0.0260 (7)0.0180 (5)0.0247 (7)
F10.0541 (6)0.0745 (8)0.1170 (10)0.0151 (6)0.0509 (7)0.0063 (7)
C210.0356 (7)0.0412 (8)0.0348 (7)0.0043 (6)0.0124 (6)0.0044 (6)
C220.0427 (8)0.0454 (9)0.0438 (8)0.0002 (7)0.0161 (7)0.0056 (7)
C230.0376 (8)0.0546 (10)0.0527 (9)0.0042 (7)0.0159 (7)0.0001 (8)
C240.0413 (8)0.0515 (9)0.0593 (10)0.0106 (7)0.0270 (8)0.0112 (8)
C250.0594 (10)0.0438 (9)0.0626 (11)0.0080 (8)0.0292 (9)0.0052 (8)
C260.0438 (8)0.0435 (9)0.0501 (9)0.0007 (7)0.0142 (7)0.0044 (7)
C310.0337 (7)0.0385 (8)0.0437 (8)0.0032 (6)0.0092 (6)0.0023 (6)
C320.0391 (8)0.0541 (10)0.0458 (8)0.0032 (7)0.0119 (7)0.0006 (7)
C330.0487 (9)0.0610 (11)0.0471 (9)0.0033 (8)0.0057 (7)0.0063 (8)
C340.0396 (9)0.0534 (10)0.0616 (11)0.0001 (8)0.0000 (8)0.0039 (8)
C350.0341 (8)0.0533 (10)0.0681 (11)0.0019 (7)0.0131 (8)0.0043 (9)
C360.0376 (8)0.0506 (9)0.0516 (9)0.0030 (7)0.0138 (7)0.0002 (7)
Geometric parameters (Å, º) top
S1—C11.7392 (15)C31—C321.390 (2)
S1—C111.7986 (17)C31—C361.397 (2)
C11—C121.512 (2)C32—C331.379 (2)
C12—C131.498 (2)C33—C341.382 (3)
N1—C11.4065 (18)C34—C351.376 (3)
N1—C21.3986 (18)C35—C361.385 (2)
N1—C131.4243 (19)C22—H220.93
O1—C131.1976 (19)C23—H230.93
C1—C31.365 (2)C25—H250.93
N2—C21.3023 (19)C26—H260.93
N2—C31.3943 (19)C32—H320.93
C2—C211.4772 (19)C33—H330.93
C3—C311.469 (2)C34—H340.93
C21—C221.386 (2)C11—H11A0.97
C21—C261.384 (2)C11—H11B0.97
C22—C231.381 (2)C12—H12A0.97
C23—C241.366 (2)C12—H12B0.97
F1—C241.3636 (17)C35—H350.93
C24—C251.358 (2)C36—H360.93
C25—C261.388 (2)
S1—C1—N1122.92 (11)C32—C33—C34120.54 (17)
S1—C1—C3130.76 (12)C33—C34—C35119.43 (16)
N1—C1—C3106.30 (12)C34—C35—C36120.39 (16)
C1—N1—C2105.70 (11)C31—C36—C35120.66 (16)
C1—N1—C13126.40 (12)C23—C22—H22119.5
C2—N1—C13126.84 (12)C21—C22—H22119.5
N1—C2—N2111.29 (12)C24—C23—H23121.1
N1—C2—C21125.50 (13)C22—C23—H23121.1
N2—C2—C21122.97 (13)C24—C25—H25120.7
N2—C3—C31120.03 (13)C26—C25—H25120.7
C2—N2—C3106.99 (12)C21—C26—H26119.9
C1—C3—N2109.73 (13)C25—C26—H26119.9
C1—C3—C31130.14 (14)C33—C32—H32119.6
C1—S1—C1198.08 (7)C31—C32—H32119.6
S1—C11—C12111.10 (13)C32—C33—H33119.7
C11—C12—C13115.87 (14)C34—C33—H33119.7
O1—C13—N1120.32 (14)C35—C34—H34120.3
O1—C13—C12123.08 (15)C33—C34—H34120.3
N1—C13—C12116.59 (13)C34—C35—H35119.8
C26—C21—C22119.06 (14)C36—C35—H35119.8
C26—C21—C2119.92 (14)C12—C11—H11A109.4
C22—C21—C2120.84 (14)S1—C11—H11A109.4
C21—C22—C23121.03 (15)C12—C11—H11B109.4
C22—C23—C24117.88 (15)S1—C11—H11B109.4
F1—C24—C23118.36 (16)H11A—C11—H11B108.0
F1—C24—C25118.39 (16)C13—C12—H12A108.3
C23—C24—C25123.24 (15)C11—C12—H12A108.3
C24—C25—C26118.52 (16)C13—C12—H12B108.3
C21—C26—C25120.26 (15)C11—C12—H12B108.3
C32—C31—C36118.16 (15)H12A—C12—H12B107.4
C32—C31—C3119.81 (14)C35—C36—H36119.7
C36—C31—C3122.02 (14)C31—C36—H36119.7
C31—C32—C33120.83 (15)
N1—C1—S1—C1120.39 (14)C2—N1—C13—C12176.47 (15)
C1—S1—C11—C1252.19 (13)C11—C12—C13—O1153.51 (18)
S1—C11—C12—C1361.22 (18)N1—C2—C21—C26133.05 (16)
C11—C12—C13—N127.8 (2)N2—C2—C21—C22121.96 (17)
C1—N1—C13—C1210.0 (2)N1—C2—C21—C2251.9 (2)
S1—C1—N1—C139.9 (2)C26—C21—C22—C230.6 (2)
N1—C2—N2—C30.38 (17)C2—C21—C22—C23175.68 (14)
C2—N2—C3—C10.31 (18)C21—C22—C23—C240.6 (2)
N2—C2—C21—C2653.1 (2)C22—C23—C24—C251.3 (3)
N2—C3—C31—C3222.5 (2)C22—C23—C24—F1177.39 (15)
C3—C1—N1—C20.11 (16)F1—C24—C25—C26177.91 (15)
S1—C1—N1—C2178.65 (11)C23—C24—C25—C260.8 (3)
C3—C1—N1—C13168.68 (14)C22—C21—C26—C251.1 (2)
C1—N1—C2—N20.31 (17)C2—C21—C26—C25176.26 (15)
C13—N1—C2—N2168.41 (14)C24—C25—C26—C210.4 (3)
C1—N1—C2—C21174.16 (14)C1—C3—C31—C32153.46 (17)
C13—N1—C2—C2117.1 (2)C1—C3—C31—C3625.4 (3)
C21—C2—N2—C3174.25 (14)N2—C3—C31—C36158.59 (15)
N1—C1—C3—N20.11 (17)C36—C31—C32—C330.2 (3)
S1—C1—C3—N2178.27 (12)C3—C31—C32—C33178.75 (16)
N1—C1—C3—C31176.17 (15)C31—C32—C33—C340.2 (3)
S1—C1—C3—C315.4 (3)C32—C33—C34—C350.2 (3)
C2—N2—C3—C31176.42 (14)C33—C34—C35—C360.2 (3)
C3—C1—S1—C11161.45 (16)C34—C35—C36—C310.5 (3)
C2—N1—C13—O12.3 (3)C32—C31—C36—C350.5 (2)
C1—N1—C13—O1168.73 (16)C3—C31—C36—C35178.38 (15)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C11—H11A···F1i0.972.483.256 (2)137
C22—H22···C24i0.932.853.753 (2)164
C32—H32···N20.932.582.896 (2)100
C36—H36···S10.932.673.3078 (18)126
Symmetry code: (i) x+1, y+1/2, z+1/2.

Experimental details

Crystal data
Chemical formulaC18H13FN2OS
Mr324.36
Crystal system, space groupMonoclinic, P21/c
Temperature (K)294
a, b, c (Å)11.5195 (13), 8.6516 (7), 15.9173 (11)
β (°) 109.865 (5)
V3)1492.0 (2)
Z4
Radiation typeMo Kα
µ (mm1)0.23
Crystal size (mm)0.45 × 0.45 × 0.35
Data collection
DiffractometerBruker P4
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
4084, 2938, 2501
Rint0.017
(sin θ/λ)max1)0.618
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.035, 0.093, 1.04
No. of reflections2938
No. of parameters208
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)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—C11.7392 (15)N1—C131.4243 (19)
S1—C111.7986 (17)O1—C131.1976 (19)
C11—C121.512 (2)C1—C31.365 (2)
C12—C131.498 (2)N2—C21.3023 (19)
N1—C11.4065 (18)N2—C31.3943 (19)
N1—C21.3986 (18)
S1—C1—N1122.92 (11)C1—S1—C1198.08 (7)
S1—C1—C3130.76 (12)S1—C11—C12111.10 (13)
N1—C1—C3106.30 (12)C11—C12—C13115.87 (14)
C1—N1—C2105.70 (11)O1—C13—N1120.32 (14)
C1—N1—C13126.40 (12)O1—C13—C12123.08 (15)
C2—N1—C13126.84 (12)N1—C13—C12116.59 (13)
N1—C1—S1—C1120.39 (14)C1—N1—C13—C1210.0 (2)
C1—S1—C11—C1252.19 (13)S1—C1—N1—C139.9 (2)
S1—C11—C12—C1361.22 (18)N2—C2—C21—C2653.1 (2)
C11—C12—C13—N127.8 (2)N2—C3—C31—C3222.5 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C11—H11A···F1i0.972.483.256 (2)137
C22—H22···C24i0.932.853.753 (2)164
C32—H32···N20.932.582.896 (2)100
C36—H36···S10.932.673.3078 (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

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