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ISSN: 2414-3146

2-Amino-5,5-di­methyl­thia­zol-4(5H)-one

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aGeorgia Southern University, 11935 Abercorn St., Department of Chemistry and Biochemistry, Savannah GA 31419, USA
*Correspondence e-mail: nshank@georgiasouthern.edu

Edited by J. Simpson, University of Otago, New Zealand (Received 24 April 2019; accepted 1 May 2019; online 14 May 2019)

Our work exploring the synthesis and optimization of increasingly hindered thiols led to the synthesis and crystal structure determination of the title compound, C5H8N2OS, a dimethly-substituted 4-thia­zolidinone. The mol­ecular packing exhibits a herringbone pattern with the zigzag running along the b-axis direction; the compound crystallizes as chains of hydrogen-bonded dimers formed by N—H⋯N hydrogen bonds, which build centrosymmetric R22(8) ring motifs in the crystal.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

As a result of their impressive array of biological responses and potential uses in medicine, 4-thia­zolidinones and their derivatives have been extensively investigated in recent years. Their wide range of biological relevance includes anti­cancer, anti­viral, anti­bacterial (Tripathi et al., 2014[Tripathi, A. C., Gupta, S. J., Fatima, G. N., Sonar, P. K., Verma, A. & Saraf, S. K. (2014). Eur. J. Med. Chem. 72, 52-77.]), analgesic (Kumar & Patil, 2017[Kumar, R. & Patil, S. (2017). Hygeia J. Drugs Medicines, 9, 80-97.]) and anti­psychotic (Kaur et al., 2010[Kaur, H., Kumar, S., Vishwakarma, P., Sharma, M., Saxena, K. K. & Kumar, A. (2010). Eur. J. Med. Chem. 45, 2777-2783.]) properties. The synthesis of these five-membered heterocyclic rings is well documented, and the majority of derivatives follow concise synthetic routes and provide generally good yields. However, access to new derivatives is desirable to enable researchers to further explore the utility of these biologically inter­esting pharmacophores. The title compound provides an avenue for a new substitution pattern that is not often seen in the literature, namely, a geminal dialkyl substitution at the 5-position on the ring. This motif may provide a unique utility since a more thermodynamically favored confirmation may result because of steric hindrance, especially if the thia­zolidinone is further substituted at the 2- and/or N-positions (Vigorita et al. 1979[Vigorita, M. G., Chimirri, A., Grasso, S. & Fenech, G. (1979). J. Heterocycl. Chem. 16, 1257-1261.]).

Herein we report the crystal structure of 2-amino-5,5-di­methyl­thia­zol-4(5H)-one (Fig. 1[link]). The mol­ecule is nearly planar, with the thia­zole ring r.m.s.d. being 0.027 Å. In the crystal, the mol­ecules form hydrogen-bonded dimers. The hydrogen bonding occurs between the N atoms of the thia­zole ring and the amino group with an R(8) synthon. The hydrogen bond between N2 and N1ii is characterized by an N2⋯N1 separation of 2.938 (3) Å [symmetry code: (ii) −x + 1, −y + 1, −z; Table 1[link]], with R22(8) ring motifs (Fig. 2[link]). A secondary N2⋯O1 hydrogen bond also involves the amino group and the O1 atom on a neighboring thia­zole ring, forming a C(6) motif. This hydrogen bond between N2 and O1i is characterized by an N2⋯O1 separation of 2.820 (3) Å [symmetry code: (i) x + 1, y, z; Table 1[link]]. This C11(6) hydrogen-bonding motif stitches the dimers into a chain running parallel to the a axis, Fig. 2[link]. The crystal structure exhibits a herringbone pattern with the blocks consisting of the chains of hydrogen-bonded dimers, with the zigzag running along the b-axis direction. There are no other short contacts or ππ inter­actions observed in the crystal.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N2—H2A⋯O1i 0.93 (3) 1.93 (4) 2.820 (3) 159 (3)
N2—H2B⋯N1ii 1.00 (4) 1.95 (4) 2.938 (3) 170 (3)
Symmetry codes: (i) x+1, y, z; (ii) -x+1, -y+1, -z.
[Figure 1]
Figure 1
A view of the mol­ecular structure of the title compound, with the atom labeling. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 2]
Figure 2
Crystal packing diagram of title compound viewed along [100]. Hydrogen bonds (Table 1[link]) are colored red.

Synthesis and crystallization

A round-bottom flask was equipped with a stir bar and reflux condenser and then charged with 1.0 g (6.0 mmol, 1.0 equiv.) of 2-bromo-2-methyl­propionic acid. The solid was heated to 100°C, at which point 0.57 g (7.5 mmol, 1.25 equiv.) of thio­urea was added. The whole was heated to 200°C for 1 h and then allowed to cool to room temperature. The resulting solid was purified on a silica (60 Å, 40–63 mm) column, eluting with methyl­ene chloride while slowly increasing the concentration of methanol (0–25%). Crystals were obtained by slow evaporation of the eluted aliquot. Note: the two H atoms on the nitro­gen are in non-degenerate equilibrium. NMR: 1H NMR [300 MHz, (CD3)2SO)] δ = 8.96 (bs, 0.6H, –NH2), 8.72 (bs, 1.4H, –NH2), 1.48 (s, 6H, 2 × –CH3) p.p.m.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link].

Table 2
Experimental details

Crystal data
Chemical formula C5H8N2OS
Mr 144.19
Crystal system, space group Monoclinic, P21/n
Temperature (K) 173
a, b, c (Å) 6.9440 (8), 12.1354 (16), 8.8283 (11)
β (°) 98.888 (11)
V3) 735.01 (16)
Z 4
Radiation type Mo Kα
μ (mm−1) 0.36
Crystal size (mm) 0.2 × 0.2 × 0.05
 
Data collection
Diffractometer Rigaku XtaLAB mini CCD
Absorption correction Multi-scan (CrysAlis PRO; Rigaku OD, 2018[Rigaku OD (2018). CrysAlis PRO. Oxford Diffraction/Agilent Technologies UK Ltd, Yarnton, England.])
Tmin, Tmax 0.497, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections 5107, 1681, 1126
Rint 0.055
(sin θ/λ)max−1) 0.649
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.051, 0.142, 1.08
No. of reflections 1681
No. of parameters 92
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.26, −0.35
Computer programs: CrysAlis PRO (Rigaku OD, 2018[Rigaku OD (2018). CrysAlis PRO. Oxford Diffraction/Agilent Technologies UK Ltd, Yarnton, England.]), SHELXT (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2018 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]) and OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]).

Structural data


Computing details top

Data collection: CrysAlis PRO (Rigaku OD, 2018); cell refinement: CrysAlis PRO (Rigaku OD, 2018); data reduction: CrysAlis PRO (Rigaku OD, 2018); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

2-Amino-5,5-dimethylthiazol-4(5H)-one top
Crystal data top
C5H8N2OSF(000) = 304
Mr = 144.19Dx = 1.303 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
a = 6.9440 (8) ÅCell parameters from 1205 reflections
b = 12.1354 (16) Åθ = 2.9–26.0°
c = 8.8283 (11) ŵ = 0.36 mm1
β = 98.888 (11)°T = 173 K
V = 735.01 (16) Å3Prism, clear bluish violet
Z = 40.2 × 0.2 × 0.05 mm
Data collection top
Rigaku XtaLAB mini CCD
diffractometer
1681 independent reflections
Radiation source: fine-focus sealed X-ray tube, Rigaku (Mo) X-ray Source1126 reflections with I > 2σ(I)
Graphite Monochromator monochromatorRint = 0.055
Detector resolution: 13.6612 pixels mm-1θmax = 27.5°, θmin = 2.9°
ω scansh = 88
Absorption correction: multi-scan
(CrysAlis PRO; Rigaku OD, 2018)
k = 1415
Tmin = 0.497, Tmax = 1.000l = 1110
5107 measured reflections
Refinement top
Refinement on F2Primary atom site location: dual
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.051H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.142 w = 1/[σ2(Fo2) + (0.0472P)2 + 0.1833P]
where P = (Fo2 + 2Fc2)/3
S = 1.08(Δ/σ)max < 0.001
1681 reflectionsΔρmax = 0.26 e Å3
92 parametersΔρmin = 0.35 e Å3
0 restraints
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S10.65626 (10)0.33147 (7)0.36674 (8)0.0466 (3)
N10.4105 (3)0.42897 (19)0.1509 (3)0.0397 (6)
C10.5978 (4)0.4149 (2)0.2050 (3)0.0359 (6)
O10.1162 (3)0.3771 (2)0.2117 (3)0.0605 (7)
N20.7350 (4)0.4625 (2)0.1419 (3)0.0448 (6)
C20.2946 (4)0.3738 (2)0.2359 (3)0.0406 (7)
C30.3980 (4)0.3023 (2)0.3668 (3)0.0399 (7)
C40.3565 (5)0.1815 (2)0.3269 (4)0.0562 (9)
H4A0.3970600.1648980.2278650.084*
H4B0.2165480.1672000.3206960.084*
H4C0.4290510.1346830.4064440.084*
C50.3337 (5)0.3342 (3)0.5181 (4)0.0555 (9)
H5A0.3996280.2869890.6001940.083*
H5B0.1923330.3247600.5100910.083*
H5C0.3677690.4113670.5414050.083*
H2A0.868 (5)0.453 (3)0.170 (4)0.063 (10)*
H2B0.695 (5)0.507 (3)0.047 (4)0.076 (11)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0359 (4)0.0617 (5)0.0390 (4)0.0048 (3)0.0043 (3)0.0136 (3)
N10.0319 (12)0.0451 (14)0.0409 (13)0.0031 (10)0.0019 (10)0.0083 (11)
C10.0335 (14)0.0413 (15)0.0316 (14)0.0046 (12)0.0005 (11)0.0018 (12)
O10.0305 (11)0.0752 (16)0.0729 (16)0.0014 (10)0.0013 (11)0.0222 (13)
N20.0330 (13)0.0560 (16)0.0448 (15)0.0043 (12)0.0040 (11)0.0109 (12)
C20.0324 (14)0.0459 (16)0.0412 (16)0.0017 (13)0.0016 (12)0.0046 (13)
C30.0384 (15)0.0439 (16)0.0357 (15)0.0008 (12)0.0002 (12)0.0068 (12)
C40.069 (2)0.0455 (19)0.0498 (19)0.0033 (16)0.0033 (17)0.0058 (14)
C50.063 (2)0.063 (2)0.0428 (18)0.0042 (17)0.0143 (16)0.0013 (15)
Geometric parameters (Å, º) top
S1—C11.746 (3)C3—C41.525 (4)
S1—C31.828 (3)C3—C51.522 (4)
N1—C11.326 (3)C4—H4A0.9800
N1—C21.358 (4)C4—H4B0.9800
C1—N21.310 (4)C4—H4C0.9800
O1—C21.225 (3)C5—H5A0.9800
N2—H2A0.93 (3)C5—H5B0.9800
N2—H2B1.00 (4)C5—H5C0.9800
C2—C31.533 (4)
C1—S1—C390.49 (12)C5—C3—C2110.5 (2)
C1—N1—C2111.7 (2)C5—C3—C4112.1 (3)
N1—C1—S1117.4 (2)C3—C4—H4A109.5
N2—C1—S1120.7 (2)C3—C4—H4B109.5
N2—C1—N1121.8 (2)C3—C4—H4C109.5
C1—N2—H2A126 (2)H4A—C4—H4B109.5
C1—N2—H2B118 (2)H4A—C4—H4C109.5
H2A—N2—H2B115 (3)H4B—C4—H4C109.5
N1—C2—C3116.6 (2)C3—C5—H5A109.5
O1—C2—N1123.9 (3)C3—C5—H5B109.5
O1—C2—C3119.5 (3)C3—C5—H5C109.5
C2—C3—S1103.59 (19)H5A—C5—H5B109.5
C4—C3—S1109.7 (2)H5A—C5—H5C109.5
C4—C3—C2108.7 (2)H5B—C5—H5C109.5
C5—C3—S1111.8 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2A···O1i0.93 (3)1.93 (4)2.820 (3)159 (3)
N2—H2B···N1ii1.00 (4)1.95 (4)2.938 (3)170 (3)
Symmetry codes: (i) x+1, y, z; (ii) x+1, y+1, z.
 

Acknowledgements

The authors thank Georgia Southern University for support of this work.

References

First citationDolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationKaur, H., Kumar, S., Vishwakarma, P., Sharma, M., Saxena, K. K. & Kumar, A. (2010). Eur. J. Med. Chem. 45, 2777–2783.  Web of Science CrossRef CAS PubMed Google Scholar
First citationKumar, R. & Patil, S. (2017). Hygeia J. Drugs Medicines, 9, 80–97.  CAS Google Scholar
First citationRigaku OD (2018). CrysAlis PRO. Oxford Diffraction/Agilent Technologies UK Ltd, Yarnton, England.  Google Scholar
First citationSheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationTripathi, A. C., Gupta, S. J., Fatima, G. N., Sonar, P. K., Verma, A. & Saraf, S. K. (2014). Eur. J. Med. Chem. 72, 52–77.  Web of Science CrossRef CAS PubMed Google Scholar
First citationVigorita, M. G., Chimirri, A., Grasso, S. & Fenech, G. (1979). J. Heterocycl. Chem. 16, 1257–1261.  CrossRef CAS Web of Science Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

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