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Journal of Chemical Crystallography

, Volume 39, Issue 2, pp 151–156 | Cite as

Low Temperature Crystal Structures of Two Rhodanine Derivatives, 3-Amino Rhodanine and 3-Methyl Rhodanine: Geometry of the Rhodanine Ring

  • Saima Jabeen
  • Rex A. Palmer
  • Brian S. Potter
  • Madeleine Helliwell
  • Trevor J. Dines
  • Babur Z. Chowdhry
Original Paper

Abstract

Rhodanines (2-thio-4-oxothiazolidines) are synthetic small molecular weight organic molecules with diverse applications in biochemistry, medicinal chemistry, photochemistry, coordination chemistry and industry. The X-ray crystal structure determination of two rhodanine derivatives, namely (I), 3-aminorhodanine [3-amino-2-thio-4-oxothiazolidine], C3H4N2OS2, and (II) 3-methylrhodanine [3-methyl-2-thio-4-oxothiazolidine], C4H5NOS2, have been conducted at 100 K. I crystallizes in the monoclinic space group P21/n with unit cell parameters a = 9.662(2), b = 9.234(2), c = 13.384(2) Å, β = 105.425(3)°, V = 1151.1(3) Å3, Z = 8 (2 independent molecules per asymmetric unit), density (calculated) = 1.710 mg/m3, absorption coefficient = 0.815 mm−1. II crystallizes in the orthorhombic space group Iba2 with unit cell a = 20.117(4), b = 23.449(5), c = 7.852(2) Å, V = 3703.9(12) Å3, Z = 24 (three independent molecules per asymmetric unit), density (calculated) = 1.584 mg/m3, absorption coefficient 0.755 mm−1. For I in the final refinement cycle the data/restraints /parameter ratios were 2639/0/161, goodness-of-fit on F2 = 0.934, final R indices [I > 2sigma(I)] were R1 = 0.0299, wR2 = 0.0545 and R indices (all data) R1 = 0.0399, wR2 = 0.0568. The largest difference peak and hole were 0.402 and −0.259 e Å−3. For II in the final refinement cycle the data/restraints/parameter ratios were 3372/1/221, goodness-of-fit on F2 = 0.950, final R indices [I > 2sigma(I)] were R1 = 0.0407, wR2 = 0.1048 and R indices (all data) R1 = 0.0450, wR2 = 0.1088. The absolute structure parameter = 0.19(9) and largest difference peak and hole 0.934 and −0.301 e Å−3. Details of the geometry of the five molecules (two for I and three for II) and the crystal structures are fully discussed. Corresponding features of the molecular geometry are highly consistent and firmly establish the geometry of the rhodanine ring.

Index Abstract

Low temperature X-ray structures of (I) 3-aminorhodanine [3-amino-2-thio-4-oxothiazolidine] and (II) 3-methylrhodanine3-methyl-2-thio-4-oxothiazolidine are presented. Crystals of I are monoclinic and occupy space group P21/n with eight molecules (2 per asymmetric unit cell) and (II) is orthorhombic in space group Iba2 with 24 molecules (3 per asymmetric unit). This study has provided five highly consistent copies of the rhodanine ring at high resolution thus enabling its geometry to be established with confidence.

The two independent molecules in the asymmetric unit of 3-aminorhodanine (left) and the three independent molecules in the asymmetric unit of 3-methylrhodanine (right) showing space filling and van der Waals contacts (drawn with MERCURY [Bruno et al. Acta Cryst B58:389, 2002]).

Keywords

Rhodanine derivative Crystal structure Low temperature Ring geometry Rhodanine 3-Aminorhodanine 3-Methylrhodanine Accurate crystal structures Geometry of the rhodanine ring 

Introduction

Rhodanine [2-thio-4-oxothiazolidine (Rd)] and its derivatives, 3-aminorhodanine (I) [3-amino-2-thio-4-oxothiazolidine (H2NRd)] and 3-methylrhodanine (II) [3-methyl-2-thio-4-oxothiazolidine (MeRd)], are five-membered ring heterocyclic systems (Fig. 1) with diverse applications particularly in biochemistry, medicinal chemistry, photochemistry, industry, and coordination chemistry. Intriguingly the parent Rd structure is not prevalent in natural molecules, but the Rd moiety can be synthesized by various methods. The classification of Rd derivatives is based solely on whether the 2-thioxo-4-oxothiazolidine ring is linked to the rest of the molecule through an exocyclic double bond or via a single bond at the 5 position. Rd derivatives are potent and selective inhibitors against dual-specificity phosphatases [1] and Mycobacterium tuberculosis [2]. Furthermore the amino and N-methyl derivatives of Rd act as mimics [3] of a common, naturally occurring cellular ligand: NAD+ (which is a common co-enzyme for many oxidoreductase enzymes). Rd derivatives also exhibit anti-diabetic [4], anti-fungal [5], anti-microbial [6], antimiotic [7], hypoglycemic [8], and anti-hyperlipaemic activity [9].
Fig. 1

Schematic chemical structure and atom numbering for (I) H2NRd and (II) MeRd

Rd derivatives are used as precursors of cyclic cis amides of α-amino acids and can be easily condensed with aldehydes. The C-5 active methylene group acts as a nucleophile in aldol condensations [10]. The use of microwave irradiation resulted in shortened reaction times, and increased yields in the aldol condensation of 3-formylchromones and 5-arylfuran-2-carboxaldehydes with the active methylene moiety of Rd derivatives in different reaction media [11]. Rd derivatives have also been used to facilitate the synthesis of 1, 3-oxathiolanes, where the thiocarbonyl moiety (C=S) acts as a nucleophile, and the reaction proceeds with high regio- and stereo-selectivity via an SN2-type mechanism [12]. Interestingly, Rd and its derivatives have been used as important reagents in coordination chemistry. They form coordination complexes with, for example, Cu+, Ag+, Au3+ as well as other metal ions [13]. The carbonyl oxygen of the Rd moiety constitutes the chelating backbone in most complexes, and allows the formation of the enol form via the displacement of a proton. Photochemical reactions of Rd derivatives with metal complexes have revealed that rhodanine ligands act as mono-dentate ligands coordinating via the sulfur (C=S) donor atom [14].

A detailed experimental study of the FT-IR, dispersive Raman, surface enhanced Raman spectroscopy, and DFT calculations (of the energy/geometry optimized structure in the gas phase) of Rd molecules together with simulated FT-IR and Raman spectra as well as calculations of the potential energy distributions for the vibrational bands (using normal coordinate analysis) has been recently undertaken [15]. Herein the X-ray crystallographic structures of the two rhodanine derivatives (I) H2NRd and (II) MeRd are presented and compared. Although the structure of the parent compound rhodanine (III; Rd, C3H3N1O1S2) has been reported [16], it is a rather poor structure [monoclinic, space group P21/n, unit cell a = 10.02, b = 7.67, c = 7.28 Å, β = 102.63°, V = 545.95 Å3, Z = 4 molecules per unit cell = one per asymmetric unit. Room temperature data collection, R = 0.14 (isotropic refinement)].

Experimental

Data Collection

Crystals of both (I) and (II) were grown from solutions in 50/50 by volume mixtures of ethanol/methanol which were allowed to evaporate slowly, alternating between 4°C and room temperature, over a period of 4 weeks.

Crystals of dimensions 0.25 × 0.20 × 0.20 mm3 (I) and 0.60 × 0.45 × 0.40 mm3 (II), respectively were chosen for study. Intensity data were collected for each of the crystals using monochromated MoKa radiation, l = 0.71073 Å on a Bruker Smart APEX CCD diffractometer and processed with the SAINT data processing program [17, 18]. The diffractometer was equipped with an Oxford Cryosystems “Cryostreams” 700 [19], enabling the data to be collected at 100 K. The crystals of (I) are monoclinic, occupy space group P21/n, and with unit cell a = 9.662(2), b = 9.233(7), c = 13.384(2) Å, β = 105.425(3)°, V = 1151.1(3) Å3, Z = 8 (two molecules per asymmetric unit) and density (calculated) = 1.710 mg/m3 and a linear absorption coefficient of 0.815 mm−1. In total 6833 integrated reflections were collected, reducing to a data set of 2639 unique with R(int) = 0.0374, and completeness of data (to theta = 25.10°) of 97.3 %. The resolution range was 8.74–0.75 Å. The crystals of (II) are orthorhombic, occupy space group Iba2, with unit cell: a = 20.117(4), b = 23.449(5), c = 7.8518(15) Å, α = β = γ = 90°, V = 3703.9(12) Å3, Z = 24, density (calculated) = 1.584 mg/m3 and a linear absorption coefficient of 0.755 mm-1. In total 10280 reflections were collected, reducing to a data set of 3372 unique with R(int) = 0.0258 and completeness of data to theta = 26.38° of 98.6%. The resolution range was 10.80–0.80 Å. Neither crystal showed any significant variation in intensity during the course of data collection. Lorentz and polarization corrections were applied. Absorption corrections in both cases were applied using the SADABS method [18]. For (I) Tmin = 0.8222, Tmax = 0.8540, and for (II) Tmin = 0.825, Tmax = 1.000.

X-ray Structure Analyses

The two crystal structures were solved by Direct Methods and refined using SHELXTL97 [17], and subsequently SHELXL-97 [20] implemented in the WinGX system of programs [21]. Non-hydrogen atoms were refined anisotropically by full-matrix least squares methods. NH2 hydrogen atoms were located in the difference electron density and refined with respect to x,y,z and Uiso. CH2 protons were set geometrically in riding mode. Isotropic temperature factors on all N-bonded H atoms refined to acceptable values.

Geometrical calculations were made with the programs PARST and PLATON [22] as implemented in WinGX. The program MERCURY [23] was used to prepare Figs. 2 and 3.
Fig. 2

(a) Structure I asymmetric unit showing molecules A and B and local H-bonding (drawn using MERCURY [23]). (b) Structure II asymmetric unit showing molecules A, B and C and local van der Waals contacts. Thermal ellipsoids are at 80 % probability (drawn using MERCURY [23])

Fig. 3

(a) 3-aminorhodanine (I) structure showing H-bonds (drawn with MERCURY [23]). (b) 3-methylrhodanine (II) showing crystal packing (drawn with MERCURY [23])

For (I), in the final refinement cycles there were 2639 data to 161 parameters, resulting in a final Goodness-of-fit on F2 of 0.857 and final R indices [I > 2sigma(I)] of R1 = 0.0296, wR2 = 0.0593. The largest and smallest difference electron density regions were 0.416 and −0.242 e Å−3, respectively. For (II), in the final refinement cycles there were 3372 data to 221 parameters, resulting in a final Goodness-of-fit on F2 of 0.950 and final R indices [I > 2sigma(I)] of R1 = 0.0407, wR2 = 0.1048. The Flack parameter [24] = 0.19(9) was refined in the full matrix least-squares process using the TWIN/BASF option. The largest and smallest difference electron density regions were 0.934 and −0.301 e Å−3, respectively. Crystal data are summarized in Table 1.
Table 1

Crystal data for (I) H2NRd and (II) MeRd

 

(I) H2NRd

(II) MeRd

Identification code

(I) H2NRd

(II) MeRd

Empirical formula

C3H4N2OS2

C4H5NOS2

Formula weight

148.20

147.21

Temperature

100(2) K

100(2) K

Wavelength

0.71073 Å

0.71073 Å

Crystal system

Monoclinic

Orthorhombic

Space group

P21/n

Iba2

Unit cell dimensions

a = 9.662(2) Å, α = 90°

a = 20.117(4) Å, α = 90°

 

b = 9.234(2) Å, β = 105.425(3)°

b = 23.449(5) Å, β = 90°

 

c = 13.384(2) Å, γ = 90°

c = 7.852(2) Å, γ = 90°

Volume

1151.1(3)Å3

3703.9(12) Å3

Z

8 (2 per asymmetric unit)

24 (3 per asymmetric unit)

Density (calculated)

1.710 mg/m3

1.584 mg/m3

Absorption coefficient

0.815 mm−1

0.755 mm−1

F(000)

608

1824

Crystal size

0.25 × 0.20 × 0.20 mm3

0.60 × 0.45 × 0.40 mm3

Theta range for data collection

2.33–28.25°

2.02–26.38°

Index ranges

−12 ≤ h ≤ 12, −12 ≤ k ≤ 7, −17 ≤ l ≤ 17

−25 ≤ h ≤ 24, −29 ≤ k ≤ 24, −9 ≤ l ≤ 7

Reflections collected

6833

10280

Independent reflections

2639 [R(int) = 0.0374]

3372 [R(int) = 0.0258]

Completeness to theta = 25.00°

97.3%

98.6%

Max. and min. transmission

0.854 and 0.822

0.825 and 1.000

Refinement method

Full-matrix least-squares on F2

Data/restraints/parameters

2639/0/161

3372/1/221

Goodness-of-fit on F2

0.934

1.032

Final R indices [I > 2sigma(I)]

R1 = 0.0299, wR2 = 0.0545

R1 = 0.0407, wR2 = 0.1088

R indices (all data)

R1 = 0.0399, wR2 = 0.0568

R1 = 0.0450, wR2 = 0.1088

Largest diff. peak and hole

0.402 and −0.259 e Å−3

0.932 and −0.304 e Å−3

FLACK parameter

Not applicable

0.19(9) refined with TWIN/BASF

Results and Discussion

Crystallographic Studies

Figures 1a and b show the chemical schemes and atom numbering for (I) H2NRd and (II) MeRd. MERCURY [23] views of the molecular structures in (I) and (II), respectively are shown in Figure 2.

Molecular Geometry

Bond lengths in (I) are determined approximately to ±0.002Å and bond angles to ±(0.1–0.2°) and in (II) the corresponding values are ±0.004Å and ±(0.1–0.2°), respectively. Structure I has two independent molecules per asymmetric unit and II has three. In view of the similarities in the two chemical molecules, most bonds, with the exception of the different side-groups to N(3), Fig. 1, occur five times each within the present study. These repeated similarities provide an opportunity to make a detailed analysis of the features of molecular geometry, observed here under comparable experimental conditions. Bond lengths and angles are summarized in Tables 2 and 3 respectively.
Table 2

Bond lengths (Å) for (I) molecules A and B and (II) molecules A, B and C

Bond

Molecule (IA)

Molecule (IB)

Molecule (IIA)

Molecule (IIB)

Molecule (IIC)

S1–C2

1.736(2)

1.728(2)

1.748(4)

1.749(4)

1.742(4)

S1–C5

1.808(2)

1.803(2)

1.798(4)

1.791(4)

1.800(3)

S2–C2

1.646(2)

1.643(2)

1.638(4)

1.642(4)

1.639(4)

O4–C4

1.210(2)

1.207(2)

1.201(5)

1.200(4)

1.196(4)

N3–C2

1.359(2)

1.337(2)

1.368(4)

1.355(4)

1.368(4)

N3–C4

1.387(2)

1.390(2)

1.394(6)

1.384(5)

1.385(5)

N3–N31

1.407(2)

1.413(2)

C4–C5

1.494(2)

1.505(2)

1.499(4)

1.513(4)

1.505(4)

N3–C31

1.464(4)

1.457(3)

1.462(4)

Table 3

Bond angles (º) for (I) molecules A and B and (II) molecules A, B and C

Angle

Molecule (IA)

Molecule (IB)

Molecule (IIA)

Molecule (IIB)

Molecule (IIC)

C2–S1–C5

92.9(1)

93.3(1)

93.1(2)

93.3(2)

93.0(2)

S1–C5–C4

107.2(1)

107.4(1)

107.2(3)

106.6(3)

107.0(3)

C5–C4–N3

110.8(2)

110.6(1)

111.6(3)

111.3(3)

111.4(3)

C4–N3–C2

118.3(1)

117.7(1)

117.1(3)

117.8(3)

117.3(3)

N3–C2–S1

110.8(1)

111.0(1)

111.1(3)

110.8(3)

111.1(3)

C5–C4–O4

127.4(2)

125.3(2)

125.1(4)

124.9(4)

125.0(4)

O4–C4–N3

121.8(2)

124.1(2)

123.3(3)

123.7(3)

123.6(3)

C4–N3–N31

119.5(1)

119.4(1)

C4–N3–C31

120.9(3)

120.8(3)

121.4(3)

N31–N3–C2

121.6(1)

122.9(1)

C41–N4–C5

122.0(3)

121.2(3)

121.2(3)

N3–C2–S2

124.8(1)

125.0(1)

126.3(3)

126.7(3)

126.6(3)

S2–C2–S1

124.4(1)

124.0(1)

122.7(2)

122.5(2)

122.2(2)

Bond Lengths

C–S bonds are discussed below. Each of the other bonds are all both self-consistent in length ie corresponding bonds in the five molecules show no significant variations, and conform to expected values [25]. The sp3 hybridized C(5) prevents ring aromaticity. C(5)–C(4) and C(5)–S(1) are effectively “single bonds”, which is evident by their relatively longer bond lengths. C(5) however does nevertheless not significantly deviate from the ring plane in any of the five molecules (see below).

C–S Bonds

There are three different types of C–S bond: S(1)–C(2) and S(1)–C(5) in the five-membered ring, and the side group bond C(2)–S(2). All three types are each highly consistent with respect to length, and have three quite distinct average values: S(1)–C(2) = 1.741(8), S(1)–C(5) = 1.800(6) and C(2)–S(2) = 1.641(3)Å, depending on their respective state of delocalization.

Bond Angles

In the five membered ring corresponding bond angles have highly consistent values (Table  3). C(2)–S(1)–C(5) has the smallest average value of 93.1(1)º and C(4)–N(3)–C(2) the largest average value of 117.6(5)º.

The high consistency in these results is a clear indication that these analyses have firmly established the geometry of the Rd (III) ring.

Ring Conformations

All five rings are essentially planar with all of the torsion angles very close to 0 or 180º.

In I the rms deviation of the five ring atoms from the ring plane of molecule A is 0.0047Å, and for ring B 0.0069Å. The non-ring atoms are all very close to the ring planes with N(31A) the most displaced by 0.174(2)Å. In II the rms deviation of the five ring atoms from the ring plane of molecule A is 0.0012Å, for ring B 0.0145Å, and for ring C 0.0181Å. The non-ring atoms are all very close to the ring planes with S(2C) the most displaced by 0.115(4)Å.

Crystal Packing

The crystal packing in I is governed by hydrogen bonding, all potential H-bond acceptors and donors taking part in this scheme. H-bond geometry is given in Table 4 and the crystal packing is illustrated in Fig. 3a. The crystal packing in II which is completely governed by van der Waals’ forces is illustrated in Fig. 3b.
Table 4

Hydrogen bonds for I [Å and °]

D–H…A

d(D–H)

d(H…A)

d(D…A)

<(DHA)

N(31A)–H(311)…O(4B)

0.93(2)

2.29(2)

2.937(2)

126.5(15)

N(31A)–H(312)…N(31B)

0.90(2)

2.36(2)

3.010(2)

129.0(16)

N(31B)–H(321)…O(4A)#1

0.88(2)

2.33(2)

3.020(2)

135.8(15)

N(31B)–H(321)…S(1B)#2

0.88(2)

2.93(2)

3.635(2)

138.1(14)

N(31B)–H(322)…N(31A)#3

0.80(2)

2.32(2)

3.095(2)

162.5(17)

Symmetry transformations used to generate equivalent atoms: #1 x − 1/2, −y + 1/2, z − 1/2; #2 −x, − y + 1, −z ; #3 −x + 1, −y + 1, −z

Other Rhodanine Structures

The crystal structure of rhodanine is known at room temperature [16] and at 173 K [26]. A room temperature structure of 3-amino rhodanine, I, [27] is also known, but erroneously describes the two molecules in the asymmetric unit of space group P21/n as lying on m-planes perpendicular to z.

Supplementary Material

Crystallographic data (excluding structure factors) for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication nos. CCDC 679332 & 679333. Copies of available material can be obtained, free of charge, on application to the Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44-(0) 1223-336033 or e-mail: teched@chemcrys.cam.ac.uk).

References

  1. 1.
    Cutshall NS, Oday C, Prezhdo M (2005) Bioorg Med Chem Lett 15:3374CrossRefGoogle Scholar
  2. 2.
    Brown CF, Bradsher CK, Moser BF, Forrester S (1959) J Org Chem 24:1056CrossRefGoogle Scholar
  3. 3.
    Lin Y (2003) US Pat. 0009526 AI Chem AbstrGoogle Scholar
  4. 4.
    Peet PN (2000) IDrugs 3:131Google Scholar
  5. 5.
    Sakagami Y, Kumeda Y, Shibata M (1998) Biosci Biotech Biochem 62:1025CrossRefGoogle Scholar
  6. 6.
    Gorishniy VY, Lesyk RB (1994) Farm ZH (Kiev) 2:52Google Scholar
  7. 7.
    Khang N, Minh LV, Vinh NN, Binh TM, Kohi PG, Dong BN, Lien NK, Lien BK (1988) Chem Abstr 109:73374Google Scholar
  8. 8.
    Clark DA, Goldstein SW, Hulin B (1992) US Pat 5 036079 Chem Abstr 116:83663Google Scholar
  9. 9.
    Hindley RM, Haigh D, Cottam GP (1992) PCT Int Appl WO 92 07 839 Chem Abstr 117:212490Google Scholar
  10. 10.
    Ravindran G, Muthusubramanian S, Selvaraj S, Perumal S (2007) Phosporhous Sulfur Silicon Relat Elem 182:321CrossRefGoogle Scholar
  11. 11.
    Gasparova R, Lacova M (2005) Mol 10:937Google Scholar
  12. 12.
    Fu C, Thrane MV, Linden A, Heimgartner H (2004) Tetrahedron 60:5407CrossRefGoogle Scholar
  13. 13.
    Fabretti AC, Franchini G, Peyronel G, Ferrari M (1982) Polyhedron 1:633CrossRefGoogle Scholar
  14. 14.
    Subasi E, Ercag A, Sert S, Senturk OS (2006) Synth React Inorg Met Org Chem 36:705CrossRefGoogle Scholar
  15. 15.
    Jabeen S (2007) PhD Thesis, University of Greenwich, UKGoogle Scholar
  16. 16.
    Helm D, Lessor AE, Merritt LL (1962) Acta Cryst 15:1227CrossRefGoogle Scholar
  17. 17.
    Bruker (2001) SMART (Version 5.625), SADABS (Version 2.03a) and SHELXTL (Version 6.12). Bruker AXS Inc., Madison, Wisconsin, USAGoogle Scholar
  18. 18.
    Bruker (2002) SAINT. Version 6.36a. Bruker AXS Inc. Madison, Wisconsin, USAGoogle Scholar
  19. 19.
    Cosier J, Glazer MJ (1986) J Appl Cryst 19:105CrossRefGoogle Scholar
  20. 20.
    Sheldrick GM (1997) SHELXL-97. Program for Crystal Structure Refinement. Univiversity of Göttingen, GermanyGoogle Scholar
  21. 21.
    Farrugia LJ (1999) J Appl Cryst 32:837CrossRefGoogle Scholar
  22. 22.
    Spek AL (1990) Acta Crystallogr A46:C34Google Scholar
  23. 23.
    Bruno IJ, Cole JC, Edgington PR, Kessler MK, Macrae CF, McCabe P, Pearson J, Taylor R (2002) Acta Cryst B58:389Google Scholar
  24. 24.
    Flack HD (1983) Acta Cryst A39:876–881Google Scholar
  25. 25.
    Ladd MFC, Palmer RA (2003) Structure determination by X-ray crystallography, 4th edn. Klewer-Plenum, NY, p. 503Google Scholar
  26. 26.
    Ng SW (2007) Acta Cryst E63:o1363–o1364Google Scholar
  27. 27.
    Zhou Q-L, Zhang Z-H, Jing Z-L (2007) Acta Cryst E63:o3000Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Saima Jabeen
    • 1
  • Rex A. Palmer
    • 2
  • Brian S. Potter
    • 2
  • Madeleine Helliwell
    • 3
  • Trevor J. Dines
    • 4
  • Babur Z. Chowdhry
    • 1
  1. 1.School of ScienceUniversity of Greenwich, (Medway Campus)Chatham Maritime, KentUK
  2. 2.School of Crystallography, Birkbeck CollegeUniversity of LondonLondonUK
  3. 3.School of ChemistryUniversity of ManchesterManchesterUK
  4. 4.Division of Electronic Engineering & PhysicsUniversity of DundeeDundeeUK

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