tert-Butyl N-[6-(N,N-dipropyl­carbamo­yl)-1,3-benzothia­zol-2-yl]carbamate

Xin Fang; Can Lei; Hai-Yang Yu; Ming-Dong Huang; Jun-Dong Wang

doi:10.1107/S160053681001528X

. 2010 Apr 30;66(Pt 5):o1239–o1240. doi: 10.1107/S160053681001528X

tert-Butyl N-[6-(N,N-dipropylcarbamoyl)-1,3-benzothiazol-2-yl]carbamate

Xin Fang ^a, Can Lei ^a, Hai-Yang Yu ^a, Ming-Dong Huang ^b, Jun-Dong Wang ^a,^*

PMCID: PMC2979059 PMID: 21579259

Abstract

The title compound C₁₉H₂₇N₃O₃S, crystallizes with two unique molecules in the asymmetric unit. The benzene ring of each benzothiazole unit carries a dipropylcarbamoyl substituent in the 6-position and a tert-butyl carbamate unit on each thiazole ring. In the crystal structure, intermolecular N—H⋯N and weak C—H⋯O hydrogen bonds form centrosymmetric dimers. Additional C—H⋯O contacts construct a three-dimensional network. A very weak C—H⋯π contact is also present.

Related literature

For benzothiazole derivatives with anti-tumor activity, see: Brantley et al. (2004 ▶); Ćaleta et al. (2009 ▶); Mortimer et al. (2006 ▶) and for benzothiazolines with anti-tuberculous properties, see: Palmer et al. (1971 ▶). For related benzothiazole structures, see: Lynch (2002 ▶); Matković-Čalogović et al. (2003 ▶); Lei et al. (2010 ▶).

Experimental

Crystal data

C₁₉H₂₇N₃O₃S
M _r = 377.50
Orthorhombic,
a = 14.068 (3) Å
b = 20.942 (4) Å
c = 26.515 (5) Å
V = 7812 (3) Å³
Z = 16
Mo Kα radiation
μ = 0.19 mm⁻¹
T = 113 K
0.45 × 0.35 × 0.23 mm

Data collection

Rigaku Saturn 724 CCD area-detector diffractometer
Absorption correction: numerical (NUMABS; Higashi, 2000 ▶) T _min = 0.993, T _max = 0.995
62834 measured reflections
8937 independent reflections
8783 reflections with I > 2σ(I)
R _int = 0.049

Refinement

R[F ² > 2σ(F ²)] = 0.055
wR(F ²) = 0.114
S = 1.27
8937 reflections
469 parameters
H-atom parameters constrained
Δρ_max = 0.33 e Å⁻³
Δρ_min = −0.23 e Å⁻³

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

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S160053681001528X/sj2775sup1.cif

e-66-o1239-sup1.cif^{(29.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053681001528X/sj2775Isup2.hkl

e-66-o1239-Isup2.hkl^{(437.2KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

Cg is the centroid of the C26–C31 benzene ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯N5	0.86	2.12	2.963 (2)	168
N4—H4⋯N2	0.86	2.16	3.006 (2)	167
C8—H8⋯O4	0.93	2.59	3.461 (2)	157
C27—H27⋯O1	0.93	2.61	3.321 (2)	134
C11—H11⋯O6ⁱ	0.93	2.38	3.161 (2)	141
C28—H28⋯O3ⁱⁱ	0.93	2.61	3.292 (2)	131
C37—H37A⋯O6ⁱⁱⁱ	0.97	2.56	3.375 (3)	142
C16—H16B⋯O3^iv	0.96	2.44	3.397 (3)	177
C20—H20C⋯O2^v	0.96	2.61	3.460 (3)	147
C22—H22A⋯Cg^vi	0.96	2.98	3.942 (3)	176

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) ; (vi) .

Acknowledgments

The authors gratefully acknowledge financial support from the Fujian Institute of Research on the Structure of Matter, State Key Laboratory of Structural Chemistry, Chinese Academy of Sciences (Nos. SZD08003 and NSFC– 30811130467), the Fujian Natural Science Foundation (No. 2008 J0330) and the Fujian Terms of Science and Technology (Nos. 2008 F5033, 2008 J1005 and 2009I0016).

supplementary crystallographic information

Comment

A number of benzothiazole derivatives have anti-tuberculous (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, the title compound was synthesized as an intermediate while its activity was not tested because it is only a fragment of our target molecule.

There are two benzothiazole molecules in one crystallographically independent unit. The benzothiazole units are similar to previously reported benzothiazole compounds (Lynch, 2002; Matković-Čalogović et al., 2003), except that the two molecules are slightly distorted from a planar conformation with the angles between thiazole and benzene rings of 1.19 (7) ° for molecule 1 (C1 >> C19) and 4.01 (6) ° for molecule 2 (C20 >> C38), respectively. The dihedral angles between the carbonylamino group and the thiazole ring are 5.43 (15) ° for 1 and 18.19 (11) ° for 2, respectively. The dihedral angles between the dipropylcarbamoyl group and the benzene ring are 56.75 (16) ° for 1 and 54.0914 (1) \5 for 2, respectively.

In the crystal, molecules form pairs via N—H···N and C—H···O hydrogen bonds, Table 1. The dimers form a network through weak C—H···O hydrogen bonds. There is also a very weak C22—H22A···Cg contact (Cg is the centroid of the C26···C31 benzene ring). No π - π interactions are found in this structure, seemingly due to the steric hindrance of the dipropylcarbamoyl group. This is in contrast to what was found in the structure of ethyl 2-(tert-butoxycarbonylamino)-1,3-benzothiazole-6-carboxylate (Lei et al., 2010).

Experimental

A solution of ethyl 2-(tert-butoxycarbonylamino)benzo[d]thiazole-6-carboxylate (2.5 g, 7.76 mmol) was refluxed in a solution of EtOH (80 ml) and 2 N aq NaOH (50 ml) for 5 hours. Then the solution was cooled to 0^oC and acidified with 1 N aq HCl solution. When pH < 2, white precipitate was collected, washed by water, and dried, afforded white solid of 2-(tert-butoxycarbonylamino)benzo[d]thiazole-6-carboxylic acid, N-Boc acid, (1.96 g, yield: 86%). 2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate, HBTU (1138 mg, 3 mmol) and N,N-Diisopropylethylamine, DIEA, (310 mg, 2.4 mmol) were added to the solution of N-Boc acid (588 mg, 2 mmol) in dry DMF (20 ml) and stired for 8 hours at room temperature, then dipropylamine (303 mg, 3 mmol) was added dropwise and the reaction continued further for 12 hours. The reaction solution was treated with water (150 ml) and then the precipitate was collected and washed with water. The filter cake was dried to yield a yellow solid and purification was achieved by column chromatography (ethyl acetate/petroleum ether 1 : 2) to yield the final product as a white solid (600 mg, yield: 79.58%). The solid was dissolved again in DMF, and filtered. After the solvent evaporated slowly at room temperature for a week, colourless rhombic crystals suitable for X-ray structure analysis were separated from the solution.