2-(1-Piperidinyl)-1,3-benzo­thia­zole

Alvarez, R.G.; Kennedy, A.R.; Khalaf, A.I.; Suckling, C.J.; Waigh, R.D.

doi:10.1107/S160053680500320X

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 61| Part 3| March 2005| Pages o569-o570

https://doi.org/10.1107/S160053680500320X

2-(1-Piperidinyl)-1,3-benzothiazole

Ricardo G. Alvarez,^a Alan R. Kennedy,^a ^* Abedawn I. Khalaf,^a Colin J. Suckling ^a and Roger D. Waigh ^b

^aDepartment of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, Scotland, and ^bDepartment of Pharmaceutical Sciences, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, Glasgow G4 0NR, Scotland
^*Correspondence e-mail: a.r.kennedy@strath.ac.uk

(Received 13 January 2005; accepted 28 January 2005; online 5 February 2005)

An unusual de-alkylation reaction between 2-chlorobenzothiazole and N-ethylpiperidine gave 2-(1-piperidinyl)-1,3-benzothiazole, C₁₂H₁₄N₂S, as pale-yellow orthorhombic crystals. Discrete molecules consist of a planar benzothiazole fragment with a piperidine ring in a chair conformation.

Comment

Research into minor groove binding drugs, such as distamycin, suggests that substitution of the head group with a heterocyclic moiety could enhance the selectivity of the binding to a specific strand of DNA. Benzothiazole and benzoxazole were examined as substitutes for the formyl group of distamycin; however, unexpected products were obtained from the reaction of 2-chlorobenzoxazole and 2-chlorobenzothiazole with the tail group of distamycin analogues. The products were proved to result from a de-alkylation of the dimethylamino tail group of the DNA binding compounds, prompting investigation of the reaction of other tertiary amines in combination with 2-chlorobenzothiazole or 2-chlorobenzoxazole (Khalaf et al., 2000 ). Use of N-ethylpiperidine gave the title compound, (I), as a crystalline product.

The crystal structure of (I) consists of discrete molecules with no significant intermolecular interactions. The piperidine ring adopts a chair conformation whilst the other C, N and S atoms are coplanar [maximum deviation from the least-squares plane is 0.029 (2) Å for C1]. The bonding about N2 is distorted towards pyrimidal, with the N atom lying 0.219 (2) Å above the plane defined by its three bonded C atoms. Examination of the bond lengths and angles confirms the double-bond character between N1 and C7 [1.304 (3) Å] and shows the relative conjugation effects this bond has with N1—C2 and N2—C7 [1.395 (3) and 1.358 (3) Å, respectively]. The bonding about S1 is slightly asymmetrical [S1—C1 and S1—C7 distances of 1.739 (2) and 1.771 (2) Å, respectively], but all geometric parameters are within the expected ranges and are consistent with those found for other amine derivatives of benzothiazole (Fehlmann, 1970 ; Chen et al., 2003 ).

Figure 1
Fi. 1. The molecular structure of (I

), shown with 50% probability displacement ellipsoids.

Experimental

2-Chlorobenzothiazole (0.504 g, 2.971 mmol) and N-ethylpiperidine (1.01 g, 8.91 mmol) were heated at 403 K for 5 d. Excess reagent was removed under reduced pressure and the crude product was applied to a chromatography column. Ethyl acetate/n-hexane (1:10) was used to elute the product, which was obtained as a pale-yellow crystalline solid (0.266 g, 41% yield); m.p. 363–364 K [literature m.p. 366–368 K (Nagarajan et al., 1971 )]. R_F = 0.33; ¹H NMR (CDCl₃): δ 1.68 (6H, br, s; 3 × CH₂), 3.56 (4H, br, s, CH₂NCH₂), 7.03–7.07 (1H, dt, J = 1.1 and 7.8 Hz, ArH), 7.26–7.31 (1H, dt, J = 1.1 and 7.8 Hz, ArH), 7.55–7.759 (2H, m, ArH). ¹³C NMR (CDCl₃): δ 24.67, 25.71 (2 × C), 50.02 (2 × C), 119.21, 120.97, 121.44, 126.26, 131.12, 153.42, 169.25. IR (KBr): 2945, 2924, 2846, 1593, 1561, 1535, 1444, 1261, 762, 732 cm⁻¹.

Crystal data

C₁₂H₁₄N₂S
M_r = 218.31
Orthorhombic, Pna2₁
a = 15.3509 (6) Å
b = 11.6315 (4) Å
c = 5.9802 (2) Å
V = 1067.79 (7) Å³
Z = 4
D_x = 1.358 Mg m⁻³
Mo Kα radiation
Cell parameters from 1447 reflections
θ = 1.0–27.5°
μ = 0.27 mm⁻¹
T = 123 (2) K
Cut needle, colourless
0.50 × 0.20 × 0.08 mm

Data collection

Nonius KappaCCD diffractometer
φ and ω scans
Absorption correction: none
11 594 measured reflections
1341 independent reflections
1208 reflections with I > 2σ(I)
R_int = 0.039
θ_max = 27.5°
h = −19 → 19
k = −14 → 15
l = −7 → 7

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.028
wR(F²) = 0.065
S = 1.07
1341 reflections
136 parameters
H-atom parameters constrained
w = 1/[σ²(F_o²) + (0.0312P)² + 0.2439P] where P = (F_o² + 2F_c²)/3
(Δ/σ)_max < 0.001
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.19 e Å⁻³

Table 1
Selected geometric parameters (Å, °)

S1—C1	1.739 (2)
S1—C7	1.771 (2)
N1—C7	1.304 (3)
N1—C2	1.395 (3)
N2—C7	1.358 (3)
N2—C12	1.466 (3)
N2—C8	1.471 (3)

C1—S1—C7	88.60 (10)
C7—N1—C2	110.18 (18)
C6—C1—S1	128.72 (18)
C2—C1—S1	109.62 (15)
C3—C2—N1	125.1 (2)
N1—C2—C1	115.55 (19)
N1—C7—N2	124.30 (19)
N1—C7—S1	116.05 (15)
N2—C7—S1	119.62 (16)

H atoms were included in the riding-model approximation, with C—H distances of 0.99 and 0.95 Å for CH₂ and CH groups, respectively, and with U_iso(H) = 1.2U_eq(C). Initial refinement gave an intermediate Flack (1983 ) parameter with a large uncertainty. Thus, in the final model, Friedel pairs were merged and no Flack parameter was refined.

Data collection: DENZO (Otwinowski & Minor, 1997 ) and COLLECT (Hooft, 1988 ); cell refinement: DENZO and COLLECT; data reduction: DENZO; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997 ); molecular graphics: ORTEPII (Johnson, 1976 ); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S160053680500320X/ac6153sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S160053680500320X/ac6153Isup2.hkl

Computing details top

Data collection: DENZO (Otwinowski & Minor, 1997) and COLLECT (Hooft, 1988); cell refinement: DENZO and COLLECT; data reduction: DENZO; program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97.

2-(1-Piperidinyl)-1,3-benzothiazole top

Crystal data top

C₁₂H₁₄N₂S	D_x = 1.358 Mg m⁻³
M_r = 218.31	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pna2₁	Cell parameters from 1447 reflections
a = 15.3509 (6) Å	θ = 1.0–27.5°
b = 11.6315 (4) Å	µ = 0.27 mm⁻¹
c = 5.9802 (2) Å	T = 123 K
V = 1067.79 (7) Å³	Cut needle, colourless
Z = 4	0.50 × 0.20 × 0.08 mm
F(000) = 464

Data collection top

Nonius KappaCCD diffractometer	1208 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.039
Graphite monochromator	θ_max = 27.5°, θ_min = 2.2°
φ and ω scans	h = −19→19
11594 measured reflections	k = −14→15
1341 independent reflections	l = −7→7

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)] = 0.028	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.065	H-atom parameters constrained
S = 1.07	w = 1/[σ²(F_o²) + (0.0312P)² + 0.2439P] where P = (F_o² + 2F_c²)/3
1341 reflections	(Δ/σ)_max < 0.001
136 parameters	Δρ_max = 0.17 e Å⁻³
1 restraint	Δρ_min = −0.19 e Å⁻³

Special details top

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

	x	y	z	U_iso*/U_eq
S1	0.39332 (3)	0.01583 (4)	0.40617 (11)	0.01893 (14)
N1	0.36236 (11)	0.11262 (14)	0.0187 (3)	0.0175 (4)
N2	0.47092 (11)	0.20489 (14)	0.2309 (3)	0.0164 (4)
C1	0.31266 (14)	−0.04382 (17)	0.2381 (4)	0.0187 (5)
C2	0.30605 (13)	0.01905 (17)	0.0379 (4)	0.0169 (4)
C3	0.24705 (13)	−0.01615 (17)	−0.1252 (4)	0.0210 (5)
H3	0.2406	0.0264	−0.2597	0.025*
C4	0.19756 (13)	−0.11476 (17)	−0.0881 (5)	0.0247 (5)
H4	0.1586	−0.1407	−0.2008	0.030*
C5	0.20427 (15)	−0.17589 (18)	0.1112 (4)	0.0248 (5)
H5	0.1691	−0.2421	0.1337	0.030*
C6	0.26155 (14)	−0.14147 (18)	0.2774 (4)	0.0217 (5)
H6	0.2660	−0.1829	0.4138	0.026*
C7	0.41108 (13)	0.12077 (16)	0.1966 (4)	0.0160 (4)
C8	0.49943 (14)	0.27153 (18)	0.0350 (4)	0.0197 (5)
H8A	0.4498	0.2817	−0.0688	0.024*
H8B	0.5457	0.2287	−0.0449	0.024*
C9	0.53401 (15)	0.38887 (17)	0.1046 (4)	0.0205 (5)
H9A	0.5589	0.4281	−0.0276	0.025*
H9B	0.4852	0.4363	0.1612	0.025*
C10	0.60356 (14)	0.37909 (19)	0.2851 (4)	0.0234 (5)
H10A	0.6553	0.3391	0.2243	0.028*
H10B	0.6216	0.4568	0.3341	0.028*
C11	0.56756 (14)	0.31233 (18)	0.4830 (4)	0.0212 (5)
H11A	0.5188	0.3557	0.5507	0.025*
H11B	0.6136	0.3034	0.5976	0.025*
C12	0.53554 (13)	0.19401 (14)	0.4101 (4)	0.0190 (4)
H12A	0.5854	0.1476	0.3568	0.023*
H12B	0.5092	0.1538	0.5394	0.023*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0234 (3)	0.0157 (2)	0.0176 (2)	−0.00208 (19)	−0.0005 (3)	0.0037 (3)
N1	0.0180 (8)	0.0155 (8)	0.0189 (9)	0.0001 (7)	0.0009 (8)	0.0004 (8)
N2	0.0195 (9)	0.0149 (8)	0.0147 (9)	−0.0022 (7)	−0.0014 (8)	0.0031 (7)
C1	0.0172 (10)	0.0185 (10)	0.0203 (11)	0.0020 (8)	0.0018 (9)	−0.0023 (9)
C2	0.0161 (10)	0.0166 (9)	0.0182 (11)	0.0022 (8)	0.0019 (9)	−0.0018 (9)
C3	0.0177 (10)	0.0238 (10)	0.0214 (13)	0.0030 (8)	0.0008 (10)	−0.0036 (10)
C4	0.0177 (10)	0.0254 (10)	0.0311 (12)	−0.0013 (8)	0.0012 (13)	−0.0076 (15)
C5	0.0201 (12)	0.0188 (10)	0.0355 (14)	−0.0034 (9)	0.0057 (11)	−0.0045 (10)
C6	0.0227 (11)	0.0173 (10)	0.0253 (13)	0.0013 (9)	0.0059 (10)	0.0015 (9)
C7	0.0209 (10)	0.0118 (9)	0.0153 (10)	0.0028 (8)	0.0027 (9)	−0.0001 (9)
C8	0.0241 (11)	0.0173 (10)	0.0178 (11)	−0.0012 (9)	0.0020 (10)	0.0042 (9)
C9	0.0255 (12)	0.0172 (10)	0.0186 (11)	−0.0031 (9)	0.0014 (9)	0.0021 (10)
C10	0.0237 (12)	0.0208 (11)	0.0256 (13)	−0.0075 (9)	0.0004 (10)	0.0006 (10)
C11	0.0230 (12)	0.0214 (11)	0.0192 (11)	−0.0038 (9)	−0.0024 (10)	0.0005 (9)
C12	0.0221 (10)	0.0169 (9)	0.0179 (10)	0.0004 (7)	−0.0036 (11)	0.0018 (12)

Geometric parameters (Å, º) top

S1—C1	1.739 (2)	C6—H6	0.9500
S1—C7	1.771 (2)	C8—C9	1.523 (3)
N1—C7	1.304 (3)	C8—H8A	0.9900
N1—C2	1.395 (3)	C8—H8B	0.9900
N2—C7	1.358 (3)	C9—C10	1.522 (3)
N2—C12	1.466 (3)	C9—H9A	0.9900
N2—C8	1.471 (3)	C9—H9B	0.9900
C1—C6	1.400 (3)	C10—C11	1.519 (3)
C1—C2	1.406 (3)	C10—H10A	0.9900
C2—C3	1.393 (3)	C10—H10B	0.9900
C3—C4	1.394 (3)	C11—C12	1.525 (3)
C3—H3	0.9500	C11—H11A	0.9900
C4—C5	1.392 (4)	C11—H11B	0.9900
C4—H4	0.9500	C12—H12A	0.9900
C5—C6	1.386 (3)	C12—H12B	0.9900
C5—H5	0.9500

C1—S1—C7	88.60 (10)	C9—C8—H8A	109.4
C7—N1—C2	110.18 (18)	N2—C8—H8B	109.4
C7—N2—C12	120.40 (17)	C9—C8—H8B	109.4
C7—N2—C8	117.44 (18)	H8A—C8—H8B	108.0
C12—N2—C8	115.24 (16)	C10—C9—C8	111.80 (18)
C6—C1—C2	121.6 (2)	C10—C9—H9A	109.3
C6—C1—S1	128.72 (18)	C8—C9—H9A	109.3
C2—C1—S1	109.62 (15)	C10—C9—H9B	109.3
C3—C2—N1	125.1 (2)	C8—C9—H9B	109.3
C3—C2—C1	119.35 (19)	H9A—C9—H9B	107.9
N1—C2—C1	115.55 (19)	C11—C10—C9	109.59 (17)
C2—C3—C4	119.0 (2)	C11—C10—H10A	109.8
C2—C3—H3	120.5	C9—C10—H10A	109.8
C4—C3—H3	120.5	C11—C10—H10B	109.8
C5—C4—C3	121.1 (2)	C9—C10—H10B	109.8
C5—C4—H4	119.5	H10A—C10—H10B	108.2
C3—C4—H4	119.5	C10—C11—C12	110.86 (19)
C6—C5—C4	120.9 (2)	C10—C11—H11A	109.5
C6—C5—H5	119.5	C12—C11—H11A	109.5
C4—C5—H5	119.5	C10—C11—H11B	109.5
C5—C6—C1	118.0 (2)	C12—C11—H11B	109.5
C5—C6—H6	121.0	H11A—C11—H11B	108.1
C1—C6—H6	121.0	N2—C12—C11	110.43 (16)
N1—C7—N2	124.30 (19)	N2—C12—H12A	109.6
N1—C7—S1	116.05 (15)	C11—C12—H12A	109.6
N2—C7—S1	119.62 (16)	N2—C12—H12B	109.6
N2—C8—C9	110.99 (18)	C11—C12—H12B	109.6
N2—C8—H8A	109.4	H12A—C12—H12B	108.1

C7—S1—C1—C6	178.0 (2)	C2—N1—C7—S1	−0.2 (2)
C7—S1—C1—C2	0.49 (15)	C12—N2—C7—N1	−166.66 (19)
C7—N1—C2—C3	−178.02 (19)	C8—N2—C7—N1	−17.2 (3)
C7—N1—C2—C1	0.6 (2)	C12—N2—C7—S1	15.4 (3)
C6—C1—C2—C3	0.3 (3)	C8—N2—C7—S1	164.88 (14)
S1—C1—C2—C3	177.97 (16)	C1—S1—C7—N1	−0.19 (17)
C6—C1—C2—N1	−178.43 (19)	C1—S1—C7—N2	177.93 (17)
S1—C1—C2—N1	−0.7 (2)	C7—N2—C8—C9	156.20 (18)
N1—C2—C3—C4	176.92 (19)	C12—N2—C8—C9	−52.7 (2)
C1—C2—C3—C4	−1.6 (3)	N2—C8—C9—C10	52.5 (2)
C2—C3—C4—C5	2.1 (3)	C8—C9—C10—C11	−55.4 (2)
C3—C4—C5—C6	−1.1 (3)	C9—C10—C11—C12	56.9 (2)
C4—C5—C6—C1	−0.3 (3)	C7—N2—C12—C11	−155.42 (19)
C2—C1—C6—C5	0.7 (3)	C8—N2—C12—C11	54.5 (2)
S1—C1—C6—C5	−176.51 (17)	C10—C11—C12—N2	−55.8 (2)
C2—N1—C7—N2	−178.20 (19)

References

Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst. 27, 435. CrossRef Web of Science IUCr Journals Google Scholar
Chen, Z.-F., Tang, Y.-Z., Shi, S.-M., Wang, X.-W., Liang, H. & Yu, K.-B. (2003). Acta Cryst. E59, o1461–o1463. Web of Science CSD CrossRef IUCr Journals Google Scholar
Fehlmann, M. (1970). Acta Cryst. B26, 1736–1741. CSD CrossRef CAS IUCr Journals Web of Science Google Scholar
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Hooft, R. (1988). COLLECT. Nonius BV, Delft, The Netherlands. Google Scholar
Johnson, C. K. (1976). ORTEPII. Report ORNL-5138. Oak Ridge National Laboratory, Tennessee, USA. Google Scholar
Khalaf, A. I., Alvarez, R. G., Suckling, C. J. & Waigh, R. D. (2000). Tetrahedron, 56, 8567–8571. Web of Science CrossRef CAS Google Scholar
Nagarajan, K., Kulkarni, C. L. & Shah, R. K. (1971). Indian J. Chem. 9, 748–754. CAS Google Scholar
Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr and R. M. Sweet, pp. 307–326. New York: Academic Press. Google Scholar
Sheldrick, G. M. (1997). SHELXL97. University of Göttingen, Germany. Google Scholar

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