2-Isopropyl-2-(6-meth­oxy-1,3-benzo­thia­zol-2-yl)-5,5-dimethyl-1,3-thia­zolidin-4-one

Hendryk Würfel; Helmar Görls; Dieter Weiss; Rainer Beckert

doi:10.1107/S1600536813019521

. 2013 Aug 7;69(Pt 9):o1391. doi: 10.1107/S1600536813019521

2-Isopropyl-2-(6-methoxy-1,3-benzothiazol-2-yl)-5,5-dimethyl-1,3-thiazolidin-4-one

Hendryk Würfel ^a, Helmar Görls ^b, Dieter Weiss ^a, Rainer Beckert ^a,^*

PMCID: PMC3884408 PMID: 24427032

Abstract

The title compound, C₁₆H₂₀N₂O₂S₂, crystallizes with two enantiomers (A and B) in the asymmetric unit. The most noticeable difference between these two molecules is the relative orientation of the benzothiazole rings, with S—C—C—S torsion angles of −19.4 (2) (molecule A) and 100.6 (1)° (molecule B). The amide structure of the thiazolidinone rings leads to intermolecular hydrogen-bonded dimers of the R and S enantiomers.

Related literature

For chemi- and bioluminescence of firefly luciferin and related compounds, see: Jung et al. (1975 ▶); Naumov et al. (2009 ▶); White et al. (1979 ▶); Branchini et al. (2002 ▶). For structure modifications of firefly luciferin, see: Meroni et al. (2009 ▶); McCutcheon et al. (2012 ▶); Branchini et al. (2012 ▶); Würfel (2012 ▶). Luciferin and related structures are widely used in clinical and biochemical applications, see: Schäffer (1987 ▶); Kricka (1988 ▶); Josel et al. (1994 ▶); Shinde et al. (2006 ▶). All solvents were purified and dried according to Armarego & Chai (2009 ▶). graphic file with name e-69-o1391-scheme1.jpg

Experimental

Crystal data

C₁₆H₂₀N₂O₂S₂
M _r = 336.46
Triclinic,
a = 11.3755 (3) Å
b = 11.9028 (3) Å
c = 12.5261 (3) Å
α = 86.122 (1)°
β = 85.949 (1)°
γ = 89.206 (1)°
V = 1687.86 (7) Å³
Z = 4
Mo Kα radiation
μ = 0.32 mm⁻¹
T = 133 K
0.06 × 0.05 × 0.05 mm

Data collection

Nonius KappaCCD diffractometer
10948 measured reflections
7580 independent reflections
6827 reflections with I > 2σ(I)
R _int = 0.019

Refinement

R[F ² > 2σ(F ²)] = 0.039
wR(F ²) = 0.088
S = 1.08
7580 reflections
557 parameters
All H-atom parameters refined
Δρ_max = 0.37 e Å⁻³
Δρ_min = −0.28 e Å⁻³

Data collection: COLLECT (Nonius, 1998 ▶); cell refinement: DENZO (Otwinowski & Minor, 1997 ▶); data reduction: DENZO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL/PC (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536813019521/fk2073sup1.cif

e-69-o1391-sup1.cif^{(36.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813019521/fk2073Isup2.hkl

e-69-o1391-Isup2.hkl^{(370.8KB, hkl)}

Click here for additional data file.^{(6.4KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813019521/fk2073Isup3.cml

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

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2A—H1NA⋯O2B	0.81 (3)	2.15 (3)	2.9429 (19)	168 (2)
N2B—H1NB⋯O2A	0.77 (2)	2.04 (2)	2.802 (2)	173 (2)

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Acknowledgments

The authors thank Roche Diagnostics GmbH, Penzberg, for financial support.

supplementary crystallographic information

1. Comment

Luciferin, especially the class which is produced by the firefly Photinus pyralis, is of particular interest because of its bioluminescence and chemoluminescence properties (Naumov et al., 2009). Dimethyloxyluciferin, one prominent derivative which is known for its ability to emit visible light in the red region (Branchini et al., 2002), was further investigated in our group focusing on the modification on the 4-position of the thiazoline ring (Würfel, 2012). An extension of the chromophore should give rise to new dimethylluciferin derivatives with altered absorption and emission properties. The nucleophilic attack of isopropylmagnesium bromide with dimethyloxyluciferin should lead to a tertiary alcohol at the 4-position of the thiazoline ring. Subsequent dehydration reaction should form a 2-propylene substructure, thus representing a carbon extended luciferin derivative.

However, the dimethyloxyluciferin derivative did not react in this expected manner. The strong carbon nucleophile exclusively attacked the 2-position of the thiazoline ring leading, after aqueous work-up, to a racemic mixture of R,S-thiazolidines. C8 became an sp³ carbon (C8A—C1A = 1.524 (2) Å and C8B—C1B = 1.520 (2) Å), which results in the loss of the conjugation with the benzothiazole parent moiety. The thiazolidine rings are almost coplanar, with a dihedral angle of 10.32 (4)°, due to a dimer formation of the (R)- and (S)- enantiomers in the asymmetric unit. The dimer structure results from two hydrogen bonds between the amide moieties of the thiazolidine rings [N(A)—H···O(B) = 2.942 (2) Å and N(B)—H···O(A) = 2.802 (2) Å] from the two symmetry-independent molecules A and B. The most noticeable difference between these two molecules is the relative orientation of the benzothiazole moiety due to rotation around the C1—C8 bond. The resulting torsion angles S1—C1—C8—S2 are -19.4 (2)° (molecule A) and 100.6 (1)° (molecule B).

2. Experimental

All chemicals were synthesized according to given literature or purchased from commercial sources. All solvents were purified and dried according to Armarego & Chai (2009). 215 mg (8.85 mmol) of magnesium turnings in 20 ml of dry diethylether and a catalytic amount of iodine are placed in a 100 ml two-necked round-bottomed flask. 0.9 ml (9.60 mmol) 2-bromopropane was added. After a slight exothermic reaction, the mixture was refluxed for 1 h then cooled to room temperature. To that mixture 1.73 g (5.90 mmol) of 2-(6-methoxybenzothiazol-2-yl)-5,5-dimethylthiazolin-4-one in 20 ml of dry THF was added. The mixture was refluxed for 2 h, cooled to room temperature and hydrolysed with 10 g of ice and 10 ml of saturated NH₄Cl solution, then extracted with ethyl acetate (3 × 20 ml). The extract was dried over MgSO₄, filtered and distilled off. The remaining solid was purified by crystallization from n-heptane/ethyl acetate, yield: 70%, 1.43 g (4.25 mmol). 2-(6-Methoxybenzothiazol-2-yl)-5,5-dimethylthiazolin-4-one was synthesized from 2-cyano-6-methoxybenzothiazole and ethyl 2-mercapto-2-methylpropanoate according to Würfel (2012).

Light-yellow single crystals were obtained by dissolving the title compound at reflux temperature in n-heptane/ethyl acetate and, after cooling to room temperature, left alone in a closed vessel for several days. Elemental analysis, calculated for C₁₆H₂₀N₂O₂S₂: C 57.11, H 5.99, N 8.33, S 19.06%; found: C 57.25, H 6.06, N 8.46, S 19.14.