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Acta Crystallogr Sect E Struct Rep Online. 2010 April 1; 66(Pt 4): o914.
Published online 2010 March 24. doi:  10.1107/S160053681001024X
PMCID: PMC2984018

Ethyl 2-(tert-butoxy­carbonyl­amino)-1,3-benzothia­zole-6-carboxyl­ate

Abstract

In the crystal of the title compound, C15H18N2O4S, inversion dimers are formed by inter­molecular N—H(...)N hydrogen bonds and weak C—H(...)O contacts. These dimers stack up along [100] through inversion-related π–π inter­actions between thia­zole rings [centroid–centroid distance = 3.790 (2) Å] and the thia­zole and benzene rings [centroid–centroid distance = 3.845 (2) Å] and C—H(...)π contacts.

Related literature

For benzothia­zole derivatives with anti-tumor activity, see: Brantley et al. (2004 [triangle]); Ćaleta et al. (2009 [triangle]); Mortimer et al. (2006 [triangle]) and for anti-tuberculous benzothia­zolines, see: Palmer et al. (1971 [triangle]). For related benzothia­zole structures, see: Lynch et al. (2002 [triangle]); Matković-Čalogović et al. (2003 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-0o914-scheme1.jpg

Experimental

Crystal data

  • C15H18N2O4S
  • M r = 322.37
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o914-efi1.jpg
  • a = 6.3026 (13) Å
  • b = 10.791 (2) Å
  • c = 11.909 (2) Å
  • α = 80.58 (3)°
  • β = 86.61 (3)°
  • γ = 81.57 (3)°
  • V = 789.9 (3) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.22 mm−1
  • T = 293 K
  • 0.70 × 0.05 × 0.02 mm

Data collection

  • Rigaku Saturn 724 CCD area-detector diffractometer
  • Absorption correction: numerical (NUMABS; Higashi, 2000 [triangle]) T min = 0.987, T max = 0.995
  • 6644 measured reflections
  • 3469 independent reflections
  • 2412 reflections with I > 2σ(I)
  • R int = 0.049

Refinement

  • R[F 2 > 2σ(F 2)] = 0.088
  • wR(F 2) = 0.203
  • S = 1.11
  • 3469 reflections
  • 199 parameters
  • H-atom parameters constrained
  • Δρmax = 0.26 e Å−3
  • Δρmin = −0.30 e Å−3

Data collection: CrystalClear (Rigaku, 2007 [triangle]); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEX (McArdle, 1995 [triangle]); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053681001024X/si2244sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S160053681001024X/si2244Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

The authors gratefully acknowledge the financial support from Fujian Institute of Research on the Structure of Matter, State Key Laboratory of Structural Chemistry, Chinese Academy of Sciences (Nos. SZD08003 and NSFC­30811130467). Fujian Natural Science Foundation (No. 2008 J0330) and Fujian Terms of Science and Technology (Nos. 2008 F5033, 2008 J1005 and 2009I0016).

supplementary crystallographic information

Comment

Benzothiazole is an important moiety used in drug development because of its biological activities. A number of benzothiazole derivatives were shown to have anti-tumor (Brantley et al., 2004; Mortimer et al., 2006; Ćaleta et al., 2009) or anti-microbial activities (Palmer et al., 1971). During our development of 2-aminobenzothiazole-based Urokinase-Type Plasminogen Activator (uPA) inhibitors, we synthesized the title compound as an intermediate while its activity was not tested because it is only a fragment of our target molecule.

The molecular structure of the compound is shown in Fig. 1. The benzothiazole moiety in this structure is very similar to other benzothiazole compounds reported before (Lynch, 2002; Matković-Čalogović et al., 2003). The dihedral angle between the carbonylamino group and the planar central 9-membered ring system is 7.59 (6) °, and between the central rings and the ethylcarboxylate group is 7.72 (6) °, respectively.

The packing of molecules is shown in Fig. 2. Molecules form pairs via N—H···N and C—H···O hydrogen bonds over crystallographic inversion symmetry. π—π stacking and C14—H14A···Cg2 hydrogen bonds (Cg2 is the benzene ring centroid) link pairs in a stacking column. In the π—π packing, Cg1···Cg1iii is 3.790 (2) Å (Cg1 is the thiazole ring centroid and symmetry code iii = -x, 2-y, 2-z), the plane to plane distance of the two thiazole rings is 3.382 Å with an offset of 1.711 Å, Cg1···Cg2iii is 3.845 (2) Å, the perpendicular distances of Cg1 to benzene ring is 3.369 Å, and Cg2 to thiazole ring is 3.383 Å. The hydrogen bonds are listed in Table 1, and the stacking geometries calculated with PLATON (Spek, 2009).

Experimental

Di-tert-butyl dicarbonate (4.92 g, 22.5 mmol) and 4-dimethylamino pyridine (2.06 g, 16.9 mmol) were added to a solution of ethyl 2-aminebenzothiazole-6-carboxylate (the starting compound) (2.5 g, 11.3 mmol) in dry THF (300 ml), and stirred for 22 hours at room temperature. Then the solvent THF was evaporated, and the residue was extracted with 1 liter of dichloromethane. The dichloromethane washed with 1 N aq HCl, water, and brine, sequentially, and dried with Na2SO4. Further filtration and concentration yielded the dried compound as a yellow solid [2.61 g, yield: 72%]. The solid was dissolved in DMF and filtered. The DMF was evaporated slowly at room temperature for a week, giving colorless needle crystals.

Refinement

All H atoms bound to C and N atoms were refined as riding, with C—H distances in the range of 0.93 to 0.97 Å and N—H distances of 0.86 Å, with Uiso(H) = 1.2Ueq(C, N); 1.5Ueq(Cmethyl).

Figures

Fig. 1.
The molecular structure of the title compound. Displacement ellipsoids are shown at the 50% probability level. Hydrogen atoms are shown as spheres of arbitrary radii.
Fig. 2.
The packing diagram for the title compound. All hydrogen atoms have been omitted for clarity. Hydrogen bonds are indicated by dashed lines.

Crystal data

C15H18N2O4SZ = 2
Mr = 322.37F(000) = 340
Triclinic, P1Dx = 1.355 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 6.3026 (13) ÅCell parameters from 2354 reflections
b = 10.791 (2) Åθ = 12–18°
c = 11.909 (2) ŵ = 0.22 mm1
α = 80.58 (3)°T = 293 K
β = 86.61 (3)°Needle, colorless
γ = 81.57 (3)°0.70 × 0.05 × 0.02 mm
V = 789.9 (3) Å3

Data collection

Rigaku Saturn 724 CCD area-detector diffractometer3469 independent reflections
Radiation source: fine-focus sealed tube2412 reflections with I > 2σ(I)
GraphiteRint = 0.049
Detector resolution: 28.5714 pixels mm-1θmax = 27.5°, θmin = 3.3°
dtprofit.ref scansh = −7→8
Absorption correction: numerical (NUMABS; Higashi, 2000)k = −13→11
Tmin = 0.987, Tmax = 0.995l = −15→15
6644 measured reflections

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.088Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.203H-atom parameters constrained
S = 1.11w = 1/[σ2(Fo2) + (0.0613P)2 + 0.839P] where P = (Fo2 + 2Fc2)/3
3469 reflections(Δ/σ)max < 0.001
199 parametersΔρmax = 0.26 e Å3
0 restraintsΔρmin = −0.30 e Å3

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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)

xyzUiso*/Ueq
S1−0.00627 (16)0.75048 (10)0.94306 (9)0.0535 (3)
O1−0.5534 (4)0.6760 (2)1.1764 (2)0.0535 (7)
N1−0.4017 (5)0.8086 (3)1.0445 (3)0.0463 (7)
H1−0.51870.85931.05150.056*
O40.6440 (4)0.9028 (3)0.6602 (2)0.0544 (7)
N2−0.2502 (5)0.9692 (3)0.9263 (2)0.0425 (7)
O2−0.2352 (5)0.6079 (3)1.0923 (3)0.0736 (10)
O30.5621 (5)1.1131 (3)0.6102 (3)0.0702 (9)
C1−0.6011 (11)0.4579 (5)1.1729 (5)0.101 (2)
H1A−0.61430.37721.21850.151*
H1B−0.47760.44961.12210.151*
H1C−0.72750.48661.12950.151*
C2−0.3890 (9)0.5131 (6)1.3253 (5)0.113 (2)
H2A−0.40420.43301.37170.169*
H2B−0.38480.57591.37330.169*
H2C−0.25830.50501.27980.169*
C3−0.7806 (8)0.5823 (5)1.3176 (5)0.0844 (17)
H3A−0.80940.50751.36850.127*
H3B−0.89730.61041.26710.127*
H3C−0.76540.64801.36080.127*
C4−0.5758 (7)0.5525 (4)1.2490 (4)0.0599 (11)
C5−0.3848 (6)0.6882 (4)1.1045 (3)0.0497 (9)
C6−0.2382 (6)0.8519 (4)0.9732 (3)0.0426 (8)
C7−0.0652 (5)0.9890 (3)0.8612 (3)0.0410 (8)
C8−0.0223 (6)1.1047 (4)0.7995 (3)0.0483 (9)
H8−0.12131.17750.80040.058*
C90.1687 (6)1.1096 (4)0.7373 (3)0.0506 (9)
H90.19801.18660.69620.061*
C100.3196 (5)1.0007 (4)0.7350 (3)0.0448 (9)
C110.2781 (6)0.8856 (4)0.7956 (3)0.0479 (9)
H110.37690.81290.79380.057*
C120.0869 (6)0.8803 (3)0.8590 (3)0.0438 (8)
C130.5180 (6)1.0144 (4)0.6628 (3)0.0500 (9)
C140.8351 (6)0.9081 (4)0.5871 (3)0.0554 (10)
H14A0.93450.95340.61780.066*
H14B0.79820.95200.51160.066*
C150.9356 (9)0.7748 (5)0.5812 (5)0.0817 (15)
H15A1.06240.77570.53240.123*
H15B0.83570.73070.55120.123*
H15C0.97340.73260.65610.123*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.0453 (6)0.0497 (6)0.0608 (6)−0.0027 (4)0.0103 (4)−0.0027 (5)
O10.0468 (15)0.0474 (15)0.0610 (17)−0.0030 (12)0.0131 (13)−0.0014 (13)
N10.0382 (16)0.0485 (18)0.0490 (18)−0.0047 (13)0.0040 (14)−0.0009 (14)
O40.0382 (14)0.0655 (18)0.0594 (17)−0.0122 (13)0.0127 (12)−0.0099 (14)
N20.0373 (16)0.0482 (18)0.0424 (16)−0.0074 (13)−0.0003 (13)−0.0073 (14)
O20.0594 (19)0.0573 (18)0.090 (2)0.0079 (15)0.0272 (17)0.0049 (16)
O30.0549 (18)0.065 (2)0.085 (2)−0.0168 (15)0.0138 (16)0.0076 (17)
C10.128 (5)0.060 (3)0.113 (5)−0.028 (3)0.036 (4)−0.013 (3)
C20.071 (4)0.144 (6)0.099 (4)−0.015 (4)−0.011 (3)0.057 (4)
C30.072 (3)0.070 (3)0.097 (4)−0.010 (2)0.040 (3)0.013 (3)
C40.054 (2)0.049 (2)0.071 (3)−0.0094 (19)0.010 (2)0.008 (2)
C50.040 (2)0.051 (2)0.056 (2)−0.0070 (17)0.0093 (18)−0.0075 (19)
C60.0377 (18)0.049 (2)0.0417 (19)−0.0057 (15)−0.0012 (15)−0.0082 (16)
C70.0324 (17)0.047 (2)0.0438 (19)−0.0050 (15)−0.0003 (15)−0.0094 (16)
C80.0395 (19)0.046 (2)0.059 (2)−0.0067 (16)0.0004 (17)−0.0060 (18)
C90.045 (2)0.052 (2)0.055 (2)−0.0145 (17)0.0038 (18)−0.0057 (19)
C100.0319 (18)0.055 (2)0.049 (2)−0.0094 (16)0.0022 (15)−0.0106 (18)
C110.0381 (19)0.053 (2)0.050 (2)−0.0017 (16)0.0021 (16)−0.0076 (18)
C120.0391 (19)0.051 (2)0.0417 (19)−0.0065 (16)0.0012 (15)−0.0077 (16)
C130.0357 (19)0.063 (3)0.051 (2)−0.0116 (18)−0.0027 (16)−0.0047 (19)
C140.042 (2)0.073 (3)0.052 (2)−0.0156 (19)0.0139 (18)−0.012 (2)
C150.078 (3)0.081 (3)0.084 (4)−0.008 (3)0.027 (3)−0.020 (3)

Geometric parameters (Å, °)

S1—C121.738 (4)C3—C41.509 (6)
S1—C61.750 (4)C3—H3A0.9600
O1—C51.332 (4)C3—H3B0.9600
O1—C41.486 (5)C3—H3C0.9600
N1—C51.369 (5)C7—C81.396 (5)
N1—C61.382 (5)C7—C121.404 (5)
N1—H10.8600C8—C91.379 (5)
O4—C131.345 (5)C8—H80.9300
O4—C141.446 (4)C9—C101.402 (5)
N2—C61.290 (4)C9—H90.9300
N2—C71.385 (4)C10—C111.382 (5)
O2—C51.203 (5)C10—C131.487 (5)
O3—C131.205 (4)C11—C121.388 (5)
C1—C41.501 (7)C11—H110.9300
C1—H1A0.9600C14—C151.495 (6)
C1—H1B0.9600C14—H14A0.9700
C1—H1C0.9600C14—H14B0.9700
C2—C41.499 (7)C15—H15A0.9600
C2—H2A0.9600C15—H15B0.9600
C2—H2B0.9600C15—H15C0.9600
C2—H2C0.9600
C12—S1—C687.89 (18)N2—C6—S1117.2 (3)
C5—O1—C4120.7 (3)N1—C6—S1121.5 (3)
C5—N1—C6122.6 (3)N2—C7—C8125.6 (3)
C5—N1—H1118.7N2—C7—C12114.9 (3)
C6—N1—H1118.7C8—C7—C12119.5 (3)
C13—O4—C14115.5 (3)C9—C8—C7119.1 (4)
C6—N2—C7110.1 (3)C9—C8—H8120.4
C4—C1—H1A109.5C7—C8—H8120.4
C4—C1—H1B109.5C8—C9—C10121.2 (4)
H1A—C1—H1B109.5C8—C9—H9119.4
C4—C1—H1C109.5C10—C9—H9119.4
H1A—C1—H1C109.5C11—C10—C9120.1 (3)
H1B—C1—H1C109.5C11—C10—C13122.5 (3)
C4—C2—H2A109.5C9—C10—C13117.3 (3)
C4—C2—H2B109.5C10—C11—C12119.0 (4)
H2A—C2—H2B109.5C10—C11—H11120.5
C4—C2—H2C109.5C12—C11—H11120.5
H2A—C2—H2C109.5C11—C12—C7121.2 (3)
H2B—C2—H2C109.5C11—C12—S1128.9 (3)
C4—C3—H3A109.5C7—C12—S1109.9 (3)
C4—C3—H3B109.5O3—C13—O4122.8 (4)
H3A—C3—H3B109.5O3—C13—C10124.7 (4)
C4—C3—H3C109.5O4—C13—C10112.5 (3)
H3A—C3—H3C109.5O4—C14—C15107.8 (3)
H3B—C3—H3C109.5O4—C14—H14A110.1
O1—C4—C2109.9 (4)C15—C14—H14A110.1
O1—C4—C1108.4 (4)O4—C14—H14B110.1
C2—C4—C1113.7 (5)C15—C14—H14B110.1
O1—C4—C3102.9 (3)H14A—C14—H14B108.5
C2—C4—C3110.7 (5)C14—C15—H15A109.5
C1—C4—C3110.7 (4)C14—C15—H15B109.5
O2—C5—O1126.7 (4)H15A—C15—H15B109.5
O2—C5—N1123.0 (3)C14—C15—H15C109.5
O1—C5—N1110.3 (3)H15A—C15—H15C109.5
N2—C6—N1121.3 (3)H15B—C15—H15C109.5

Hydrogen-bond geometry (Å, °)

Cg2 is the centroid of the C7–C12 benzene ring.
D—H···AD—HH···AD···AD—H···A
N1—H1···N2i0.862.223.054 (14)162
C8—H8···O1i0.932.433.334 (14)164
C14—H14A···Cg2ii0.972.663.523 (18)149

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: SI2244).

References

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