4,5,6,7-Tetra­hydro­benzo[d]thia­zol-2-amine

Krasniqi, F.; Tavčar, G.; Goreshnik, E.; Popovski, E.; Jashari, A.

doi:10.1107/S2414314625009137

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 10| Part 10| October 2025| x250913

https://doi.org/10.1107/S2414314625009137

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4,5,6,7-Tetrahydrobenzo[d]thiazol-2-amine

Fatjonë Krasniqi,^a,^b ^* Gašper Tavčar,^c Evgeny Goreshnik,^c Emil Popovski ^b and Ahmed Jashari ^d,^e

^aAlma Mater Europaea Campus College, 'Rezonanca', Prishtina 10000, Republic of Kosovo, ^bInstitute of Chemistry, Faculty of Natural Sciences & Mathematics, Ss. Cyril & Methodius University, PO Box 162, Skopje 1000, Republic of North Macedonia, ^cDepartment of Inorganic Chemistry and Technology, Jožef Stefan Institute, Ljubljana, 1000, Slovenia, ^dGroup of Chemistry, Faculty of Natural Sciences & Mathematics, University of Tetovo, Tetovo 1200, Republic of North Macedonia, and ^eNanoAlb, Albanian Unit of Nanosciences and Nanotechnology, Academy of Sciences of Albania, Fan Noli square, 1000 Tirana, Albania
^*Correspondence e-mail: [email protected]

Edited by W. T. A. Harrison, University of Aberdeen, United Kingdom (Received 8 October 2025; accepted 17 October 2025; online 24 October 2025)

In the title compound, C₇H₁₀N₂S, the six-membered ring is disordered over two half-chair orientations. In the crystal, infinite [001] chains linked by N—H⋯N hydrogen bonds occur.

Keywords: crystal structure; heterocycles; Hantzsch reaction.

CCDC reference: 2496861

Structure description

Because of its many pharmacological uses, thiazole makes an excellent pharmacophore nucleus. Various biological properties such as antioxidant (Petrou et al., 2021 ) and analgesic (Ye et al., 2013 ) activities are exhibited by its derivatives. As part of our studies in this area we now report the synthesis and structure of the title compound, C₇H₁₀N₂S (Fig. 1).

Figure 1
The molecular structure of I with displacement ellipsoids drawn at 50% probability. Only the major disorder component for the C5 and C6 methylene groups is shown.

As expected, the N atom of thiazole ring demonstrates noticeable inequality of C—N bond distances [1.391 (2) for C3—N1 versus 1.303 (2) Å for C1=N1] corresponding to the presence of single and double bonds. The C2=C3 double bond is clearly shorter [1.344 (3) Å] than the other bonds in six-membered ring. The cyclohexene ring is partially disordered (C5 and C6 and their attached H atoms) over two half-chair orientations with very unequal [0.919 (4) versus 0.081 (4)] occupancies.

In the extended structure, the molecules are linked by strong N2—H2B⋯N1 hydrogen bonds (Table 1, Fig. 2) between the amino group of one molecule and the thiazole N atom of another molecule to generate infinite chains running along the crystallographic c-axis direction. Weaker N2—H2A⋯N1 bonds reinforce the chains.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2A⋯N1ⁱ	0.93 (2)	2.56 (2)	3.392 (2)	149 (2)
N2—H2B⋯N1ⁱⁱ	0.81 (2)	2.13 (2)	2.941 (2)	175 (2)
Symmetry codes: (i) $[-x+{\script{3\over 2}}, -y+{\script{1\over 2}}, z]$ ; (ii) $[x, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]$ .

Figure 2
Fragment of a [001] chain of molecules linked by N—H⋯N hydrogen bonds in the crystal structure of I.

A total of 40 structures containing a 4,5,6,7-tetrahydrobenzo[d]thiazol-2-amine core were found in a search of the Cambridge Structural Database (CSD, Version 5.45, update of March 2024; Groom et al., 2016 ). Excluding compounds with conjugated fragments and protonated salts one may find only five derivatives, namely: 6-nitro-5-phenyl-N,N-bis(propan-2-yl)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-amine (Richter et al., 2018 ), N-(6-hydroxy-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)acetamide monohydrate and N-(6-hydroxy-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)acetamide (Ciceri et al., 2020 ), 2-amino-4,4,7,7-tetramethyl-4,5,6,7-tetrahydro-1,3-benzothiazol-3-ium 4,4,7,7-tetramethyl-4,5,6,7-tetrahydro-1,3-benzothiazol-2-amine 3-carboxypropanoate (Shaibah et al., 2019 ) and 3-(4-methoxyphenyl)-2-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)prop-2-enenitrile (Dyachenko et al., 2021 ).

Synthesis and crystallization

61.13 mmol of thiourea (4.65 g) and 30.57 mmol (7.76 g) of iodine were mixed in a round-bottom flask. Then, 30.57 mmol (3 g) of cyclohexanone was added and the mixture was refluxed for 24 h at 100 °C. After 24 h, the system was taken out of the oil bath and left to cool to room temperature, meanwhile 350 ml of distilled water was heated to boiling and used in portions to dissolve the reaction mass, and everything was transferred to a crystallizing dish and left to cool to room temperature. Then, three extractions were made with 55 ml of diethyl ether to remove the unreacted ketone, I₂ and sulfur. Next, 50 ml of NH₄OH (25%) solution was added to the aqueous solution, and three extractions were made with diethyl ether (55 ml): the ethereal layers were combined, and dried over MgSO₄. After drying the organic layer was evaporated on a rotavapor. The product was obtained as a light-yellow precipitate. Colourless prisms were recrystallized from n-hexane solution. The reaction scheme is shown in Fig. 3.

Figure 3
Reaction scheme.

FTIR (ATR/cm⁻¹): 3430–3250 (NH₂, stretching), 2850–2950 (CH₂, asymmetric stretching). 3430 (NH₂, asymmetric stretching), 3250 (NH₂, symmetric stretching), 3150, 3100, 3050 (CH, aromatic stretching), 1650 (NH₂, bending deformations). ¹³C-NMR(δ/p.p.m.: 165.86, 145.35, 114,96, 26.75, 23.72, 23.17, 23.04. ¹H-NMR (DMSO-d₆, δ/p.p.m.): 6.58 (2H, s), 2.51 (2H, t), 2.50 (2H, t), 2.48 (4H, m). Elemental analysis: calculated C 54.51; H 6.54; N,18.16. Found: C 54.75; H 7.04; N 18.32. TOF MS ES+(: m/e): 155 [M + H]⁺, 177 [M + Na]⁺.

Refinement

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

Table 2
Experimental details

Crystal data
Chemical formula	C₇H₁₀N₂S
M_r	154.23
Crystal system, space group	Orthorhombic, Pccn
Temperature (K)	150
a, b, c (Å)	14.4368 (6), 13.3928 (6), 8.0734 (4)
V (Å³)	1560.99 (12)
Z	8
Radiation type	Cu Kα
μ (mm⁻¹)	3.05
Crystal size (mm)	0.42 × 0.13 × 0.09

Data collection
Diffractometer	New Gemini, Dual, Cu at home/near, Atlas
Absorption correction	Analytical (CrysAlis PRO; Rigaku OD, 2024 )
T_min, T_max	0.484, 0.782
No. of measured, independent and observed [I > 2σ(I)] reflections	4399, 1606, 1284
R_int	0.037
(sin θ/λ)_max (Å⁻¹)	0.630

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.036, 0.101, 1.00
No. of reflections	1606
No. of parameters	106
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.28, −0.23
Computer programs: CrysAlis PRO (Rigaku OD, 2024), SHELXT2014/4 (Sheldrick, 2015a ), SHELXL2016/6 (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 2496861

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314625009137/hb4540sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314625009137/hb4540Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314625009137/hb4540Isup3.cml

checkCIF report

Computing details top

4,5,6,7-Tetrahydrobenzo[d]thiazol-2-amine top

Crystal data top

C₇H₁₀N₂S	D_x = 1.313 Mg m⁻³
M_r = 154.23	Cu Kα radiation, λ = 1.54184 Å
Orthorhombic, Pccn	Cell parameters from 2022 reflections
a = 14.4368 (6) Å	θ = 4.5–75.3°
b = 13.3928 (6) Å	µ = 3.05 mm⁻¹
c = 8.0734 (4) Å	T = 150 K
V = 1560.99 (12) Å³	Prism, colourless
Z = 8	0.42 × 0.13 × 0.09 mm
F(000) = 656

Data collection top

New Gemini, Dual, Cu at home/near, Atlas diffractometer	1606 independent reflections
Radiation source: fine-focus sealed X-ray tube, Enhance (Cu) X-ray Source	1284 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.037
Detector resolution: 10.6426 pixels mm^-1	θ_max = 76.2°, θ_min = 4.5°
ω scans	h = −17→18
Absorption correction: analytical (CrysAlisPro; Rigaku OD, 2024)	k = −14→16
T_min = 0.484, T_max = 0.782	l = −9→7
4399 measured reflections

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.036	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.101	w = 1/[σ²(F_o²) + (0.0586P)² + 0.0974P] where P = (F_o² + 2F_c²)/3
S = 1.00	(Δ/σ)_max = 0.001
1606 reflections	Δρ_max = 0.28 e Å⁻³
106 parameters	Δρ_min = −0.23 e Å⁻³
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.

Refinement. 1. Fixed Uiso At 1.2 times of: All C(H,H) groups, All C(H,H,H,H) groups 2. Uiso/Uaniso restraints and constraints Uanis(C5B) = Uanis(C5A) Uanis(C6B) = Uanis(C6A) 3. Others Sof(H4BC)=Sof(H4BD)=Sof(C5B)=Sof(H5BA)=Sof(H5BB)=Sof(C6B)=Sof(H6BA)=Sof(H6BB)= Sof(H7BC)=Sof(H7BD)=1-FVAR(1) Sof(H4AA)=Sof(H4AB)=Sof(C5A)=Sof(H5AA)=Sof(H5AB)=Sof(C6A)=Sof(H6AA)=Sof(H6AB)= Sof(H7AA)=Sof(H7AB)=FVAR(1) 4.a Secondary CH2 refined with riding coordinates: C4(H4AA,H4AB), C4(H4BC,H4BD), C5A(H5AA,H5AB), C5B(H5BA,H5BB), C6A(H6AA,H6AB), C6B(H6BA,H6BB), C7(H7AA,H7AB), C7(H7BC,H7BD)

The hydrogen atoms of the amino group were localized in difference Fourier maps and refined freely. Other H-atoms were placed at calculated positions and refined as riding atoms with U_iso(H) = 1.2U_eq(carrier).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
S1	0.58597 (3)	0.40079 (3)	0.15755 (6)	0.02956 (17)
N1	0.65849 (10)	0.36334 (11)	0.44247 (18)	0.0258 (3)
N2	0.63974 (11)	0.22015 (11)	0.2777 (2)	0.0287 (3)
H2A	0.6776 (17)	0.1863 (19)	0.352 (3)	0.038 (6)*
H2B	0.6455 (17)	0.2007 (18)	0.183 (3)	0.035 (6)*
C1	0.63374 (11)	0.31960 (13)	0.3052 (2)	0.0240 (3)
C2	0.60279 (12)	0.49990 (13)	0.2947 (2)	0.0268 (4)
C3	0.64083 (11)	0.46534 (12)	0.4353 (2)	0.0244 (3)
C4	0.66431 (13)	0.53193 (13)	0.5791 (2)	0.0319 (4)
H4AA	0.724328	0.511269	0.627540	0.038*	0.919 (4)
H4AB	0.616144	0.525577	0.665786	0.038*	0.919 (4)
H4BC	0.732233	0.540469	0.588221	0.038*	0.081 (4)
H4BD	0.640952	0.502830	0.683839	0.038*	0.081 (4)
C5A	0.67030 (17)	0.64067 (15)	0.5214 (3)	0.0369 (5)	0.919 (4)
H5AA	0.673707	0.685204	0.619040	0.044*	0.919 (4)
H5AB	0.727418	0.650166	0.455371	0.044*	0.919 (4)
C5B	0.615 (2)	0.6383 (18)	0.543 (4)	0.0369 (5)	0.081 (4)
H5BA	0.546954	0.631106	0.557296	0.044*	0.081 (4)
H5BB	0.636943	0.688128	0.624377	0.044*	0.081 (4)
C6A	0.58632 (17)	0.66856 (16)	0.4168 (3)	0.0375 (6)	0.919 (4)
H6AA	0.589342	0.740445	0.388740	0.045*	0.919 (4)
H6AB	0.529217	0.657193	0.482040	0.045*	0.919 (4)
C6B	0.635 (2)	0.6745 (18)	0.373 (4)	0.0375 (6)	0.081 (4)
H6BA	0.701811	0.671058	0.350239	0.045*	0.081 (4)
H6BB	0.613909	0.744546	0.360579	0.045*	0.081 (4)
C7	0.58170 (14)	0.60702 (14)	0.2562 (3)	0.0351 (4)
H7AA	0.519122	0.612469	0.206832	0.042*	0.919 (4)
H7AB	0.627174	0.633060	0.175189	0.042*	0.919 (4)
H7BC	0.514371	0.619176	0.267818	0.042*	0.081 (4)
H7BD	0.599574	0.622040	0.140437	0.042*	0.081 (4)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0339 (3)	0.0302 (3)	0.0246 (3)	0.00217 (16)	−0.00544 (16)	−0.00116 (16)
N1	0.0307 (7)	0.0205 (7)	0.0261 (7)	−0.0012 (5)	−0.0006 (6)	−0.0002 (5)
N2	0.0369 (8)	0.0238 (7)	0.0254 (8)	−0.0029 (6)	−0.0002 (6)	−0.0022 (6)
C1	0.0226 (7)	0.0263 (8)	0.0231 (8)	−0.0018 (6)	0.0015 (6)	0.0001 (6)
C2	0.0246 (7)	0.0264 (9)	0.0293 (9)	0.0007 (6)	0.0016 (6)	−0.0011 (7)
C3	0.0238 (7)	0.0212 (7)	0.0282 (8)	−0.0008 (6)	0.0031 (6)	−0.0007 (6)
C4	0.0377 (9)	0.0239 (8)	0.0340 (10)	−0.0003 (7)	−0.0045 (7)	−0.0050 (7)
C5A	0.0385 (13)	0.0227 (9)	0.0494 (13)	−0.0015 (8)	−0.0033 (10)	−0.0075 (9)
C5B	0.0385 (13)	0.0227 (9)	0.0494 (13)	−0.0015 (8)	−0.0033 (10)	−0.0075 (9)
C6A	0.0382 (12)	0.0255 (9)	0.0489 (14)	0.0074 (9)	0.0026 (10)	−0.0016 (9)
C6B	0.0382 (12)	0.0255 (9)	0.0489 (14)	0.0074 (9)	0.0026 (10)	−0.0016 (9)
C7	0.0362 (9)	0.0293 (9)	0.0398 (11)	0.0080 (7)	−0.0002 (8)	0.0061 (8)

Geometric parameters (Å, º) top

S1—C1	1.7548 (17)	C5A—H5AA	0.9900
S1—C2	1.7453 (18)	C5A—H5AB	0.9900
N1—C1	1.303 (2)	C5A—C6A	1.524 (3)
N1—C3	1.391 (2)	C5B—H5BA	0.9900
N2—H2A	0.93 (3)	C5B—H5BB	0.9900
N2—H2B	0.81 (3)	C5B—C6B	1.48 (4)
N2—C1	1.353 (2)	C6A—H6AA	0.9900
C2—C3	1.344 (3)	C6A—H6AB	0.9900
C2—C7	1.499 (2)	C6A—C7	1.538 (3)
C3—C4	1.503 (2)	C6B—H6BA	0.9900
C4—H4AA	0.9900	C6B—H6BB	0.9900
C4—H4AB	0.9900	C6B—C7	1.51 (3)
C4—H4BC	0.9900	C7—H7AA	0.9900
C4—H4BD	0.9900	C7—H7AB	0.9900
C4—C5A	1.532 (3)	C7—H7BC	0.9900
C4—C5B	1.62 (3)	C7—H7BD	0.9900

C2—S1—C1	89.19 (8)	C6A—C5A—H5AB	109.5
C1—N1—C3	110.86 (15)	C4—C5B—H5BA	109.3
H2A—N2—H2B	113 (2)	C4—C5B—H5BB	109.3
C1—N2—H2A	114.4 (16)	H5BA—C5B—H5BB	108.0
C1—N2—H2B	118.6 (18)	C6B—C5B—C4	112 (2)
N1—C1—S1	114.00 (13)	C6B—C5B—H5BA	109.3
N1—C1—N2	124.38 (16)	C6B—C5B—H5BB	109.3
N2—C1—S1	121.56 (14)	C5A—C6A—H6AA	109.3
C3—C2—S1	109.32 (13)	C5A—C6A—H6AB	109.3
C3—C2—C7	126.01 (17)	C5A—C6A—C7	111.73 (18)
C7—C2—S1	124.62 (15)	H6AA—C6A—H6AB	107.9
N1—C3—C4	120.63 (16)	C7—C6A—H6AA	109.3
C2—C3—N1	116.63 (16)	C7—C6A—H6AB	109.3
C2—C3—C4	122.73 (16)	C5B—C6B—H6BA	110.4
C3—C4—H4AA	109.7	C5B—C6B—H6BB	110.4
C3—C4—H4AB	109.7	C5B—C6B—C7	107 (2)
C3—C4—H4BC	110.4	H6BA—C6B—H6BB	108.6
C3—C4—H4BD	110.4	C7—C6B—H6BA	110.4
C3—C4—C5A	109.98 (16)	C7—C6B—H6BB	110.4
C3—C4—C5B	106.4 (10)	C2—C7—C6A	109.22 (17)
H4AA—C4—H4AB	108.2	C2—C7—C6B	109.8 (10)
H4BC—C4—H4BD	108.6	C2—C7—H7AA	109.8
C5A—C4—H4AA	109.7	C2—C7—H7AB	109.8
C5A—C4—H4AB	109.7	C2—C7—H7BC	109.7
C5B—C4—H4BC	110.4	C2—C7—H7BD	109.7
C5B—C4—H4BD	110.4	C6A—C7—H7AA	109.8
C4—C5A—H5AA	109.5	C6A—C7—H7AB	109.8
C4—C5A—H5AB	109.5	C6B—C7—H7BC	109.7
H5AA—C5A—H5AB	108.0	C6B—C7—H7BD	109.7
C6A—C5A—C4	110.91 (18)	H7AA—C7—H7AB	108.3
C6A—C5A—H5AA	109.5	H7BC—C7—H7BD	108.2

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···N1ⁱ	0.93 (2)	2.56 (2)	3.392 (2)	149 (2)
N2—H2B···N1ⁱⁱ	0.81 (2)	2.13 (2)	2.941 (2)	175 (2)

Symmetry codes: (i) −x+3/2, −y+1/2, z; (ii) x, −y+1/2, z−1/2.

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