Experimental and theoretical investigations on a furan-2-carboxamide-bearing thia­zole: synthesis, mol­ecular characterization by IR/NMR/XRD, electronic characterization by DFT, Hirshfeld surface analysis and biological activity

Çakmak, Ş.; Koşar Kırca, B.; Veyisoğlu, A.; Yakan, H.; Ersanlı, C.C.; Kütük, H.

doi:10.1107/S2053229622002066

Experimental and theoretical investigations on a furan-2-carboxamide-bearing thiazole: synthesis, molecular characterization by IR/NMR/XRD, electronic characterization by DFT, Hirshfeld surface analysis and biological activity

Ş. Çakmak, B. Koşar Kırca, A. Veyisoğlu, H. Yakan, C. C. Ersanlı and H. Kütük

A thiazole-based heterocyclic amide, namely, N-(thiazol-2-yl)furan-2-carboxamide, C₈H₆N₂O₂S, was synthesized and investigated for its antimicrobial activity. The structure was characterized by elemental analysis and IR, ¹H NMR, and ¹³C NMR spectroscopy. The molecular and electronic structures were investigated experimentally by single-crystal X-ray diffraction (XRD) and theoretically by density functional theory (DFT) modelling. The compound crystallized in the monoclinic space group P2₁/n and the asymmetric unit contains two symmetrically independent molecules. Several noncovalent interactions were recorded by XRD and analysed with Hirshfeld surface analysis (HSA) calculations. Natural bond orbital, molecular electrostatic potential, second-order nonlinear optical and thermodynamic property analyses were also carried out using the DFT/B3LYP method. The title compound was evaluated for antimicrobial activity against eight microorganisms consisting of Gram-negative bacteria, Gram-positive bacteria and fungi. The compound showed good antimicrobial activity against the eight tested microorganisms. This suggests that the compound merits further study for potential pharmacological and medical applications.

Keywords: thiazolamide; antimicrobial activity; spectroscopic evaluation; biological activity; furan; carboxamide; XRD; Hirshfeld surface; crystal structure.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229622002066/zo3018sup1.cif Contains datablocks I, global
	Structure factor file (CIF format) https://doi.org/10.1107/S2053229622002066/zo3018Isup2.hkl Contains datablock I
	Chemical Markup Language (CML) file https://doi.org/10.1107/S2053229622002066/zo3018Isup3.cml Supplementary material

CCDC reference: 2085414

Computing details top

Data collection: APEX3 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015); molecular graphics: Mercury (Macrae et al., 2020); software used to prepare material for publication: WinGX (Farrugia, 2012).

N-(Thiazol-2-yl)furan-2-carboxamide top

Crystal data top

C₈H₆N₂O₂S	F(000) = 800
M_r = 194.21	D_x = 1.493 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
a = 11.9532 (11) Å	Cell parameters from 9964 reflections
b = 11.1161 (10) Å	θ = 2.4–28.2°
c = 13.4093 (12) Å	µ = 0.34 mm⁻¹
β = 104.071 (3)°	T = 296 K
V = 1728.3 (3) Å³	Block, colourless
Z = 8	0.17 × 0.12 × 0.11 mm

Data collection top

Bruker APEXII CCD diffractometer	R_int = 0.035
φ and ω scans	θ_max = 28.3°, θ_min = 2.4°
44822 measured reflections	h = −15→15
4276 independent reflections	k = −14→14
3424 reflections with I > 2σ(I)	l = −17→17

Refinement top

Refinement on F²	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.045	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.134	w = 1/[σ²(F_o²) + (0.0677P)² + 1.5631P] where P = (F_o² + 2F_c²)/3
S = 0.94	(Δ/σ)_max < 0.001
4276 reflections	Δρ_max = 0.41 e Å⁻³
241 parameters	Δρ_min = −0.33 e Å⁻³

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. A suitable sample of size 0.17 × 0.312 × 0.11 mm was chosen for the single crystal X-ray study. Reflections were collected in the rotation mode (ω scanning mode) and cell parameters were determined using the X-AREA software (Stoe & Cie, 2002). Absorption correction (µ = 0.339 mm^-1) was carried out using the X-RED32 software (Stoe & Cie, 2002). The structure was solved by direct methods using SHELXS2013 (Sheldrick, 2008). The refinement was carried out by full-matrix least-squares method using SHELXL2013 on the positional and anisotropic temperature parameters of the non-H atoms, or equivalently corresponding to 241 crystallographic parameters (Sheldrick, 2015). Under the condition of the I > 2σ(I) threshold, the structure was refined to R = 0.045, wR2 = 0.109, S = 0.941 with 3424 observed reflections. The other data collection conditions and parameters of refinement process are listed in Table 1.

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

	x	y	z	U_iso*/U_eq
C1	0.2190 (2)	0.6474 (2)	0.2453 (2)	0.0499 (6)
H1	0.1624	0.7060	0.2258	0.060*
C2	0.2906 (2)	0.6111 (2)	0.18791 (19)	0.0470 (5)
H2	0.2877	0.6433	0.1233	0.056*
C3	0.35429 (16)	0.49271 (16)	0.32135 (15)	0.0321 (4)
C4	0.40753 (17)	0.37067 (18)	0.47478 (16)	0.0356 (4)
C5	0.47912 (17)	0.27130 (19)	0.52414 (15)	0.0362 (4)
C6	0.4940 (2)	0.2238 (2)	0.61889 (18)	0.0490 (6)
H6	0.4588	0.2490	0.6700	0.059*
C7	0.5732 (2)	0.1285 (2)	0.62552 (19)	0.0533 (6)
H7	0.6004	0.0787	0.6819	0.064*
C8	0.6017 (2)	0.1233 (2)	0.5352 (2)	0.0516 (6)
H8	0.6528	0.0681	0.5186	0.062*
C9	0.6672 (2)	0.1397 (2)	0.19249 (18)	0.0470 (5)
H9	0.7005	0.0644	0.1902	0.056*
C10	0.5916 (2)	0.1662 (2)	0.24828 (18)	0.0455 (5)
H10	0.5674	0.1093	0.2893	0.055*
C11	0.59902 (16)	0.34353 (18)	0.17865 (15)	0.0333 (4)
C12	0.62594 (18)	0.53124 (19)	0.09742 (16)	0.0381 (4)
C13	0.59577 (19)	0.65833 (19)	0.08489 (16)	0.0391 (5)
C14	0.6377 (3)	0.7464 (2)	0.0358 (3)	0.0649 (8)
H14	0.6924	0.7379	−0.0025	0.078*
C15	0.5835 (3)	0.8537 (2)	0.0531 (2)	0.0609 (7)
H15	0.5956	0.9299	0.0291	0.073*
C16	0.5120 (3)	0.8244 (2)	0.1101 (2)	0.0694 (8)
H16	0.4643	0.8787	0.1327	0.083*
N1	0.36863 (15)	0.52284 (16)	0.23117 (14)	0.0400 (4)
N3	0.55182 (16)	0.28347 (16)	0.24137 (14)	0.0413 (4)
O1	0.33984 (15)	0.42142 (15)	0.51616 (13)	0.0518 (4)
O2	0.54529 (14)	0.21034 (15)	0.47094 (12)	0.0468 (4)
O3	0.69889 (17)	0.48864 (16)	0.05720 (15)	0.0621 (5)
O4	0.51695 (18)	0.70450 (15)	0.13144 (14)	0.0587 (5)
S1	0.24661 (5)	0.57033 (5)	0.36007 (5)	0.04299 (16)
S2	0.69414 (5)	0.26387 (5)	0.12559 (5)	0.04722 (17)
N2	0.41974 (15)	0.40403 (15)	0.37949 (13)	0.0339 (4)
H2A	0.465 (2)	0.369 (2)	0.3532 (18)	0.041*
N4	0.57260 (15)	0.46326 (15)	0.15663 (14)	0.0361 (4)
H4	0.521 (2)	0.490 (2)	0.1791 (18)	0.043*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0454 (12)	0.0394 (11)	0.0671 (15)	0.0115 (10)	0.0177 (11)	0.0092 (11)
C2	0.0462 (12)	0.0440 (12)	0.0531 (13)	0.0074 (10)	0.0167 (10)	0.0124 (10)
C3	0.0323 (9)	0.0266 (9)	0.0410 (10)	−0.0028 (7)	0.0160 (8)	−0.0047 (8)
C4	0.0369 (10)	0.0351 (10)	0.0377 (10)	−0.0059 (8)	0.0143 (8)	−0.0040 (8)
C5	0.0342 (10)	0.0393 (11)	0.0373 (10)	−0.0033 (8)	0.0133 (8)	−0.0019 (8)
C6	0.0463 (12)	0.0627 (15)	0.0406 (12)	0.0050 (11)	0.0160 (10)	0.0069 (11)
C7	0.0517 (14)	0.0583 (15)	0.0492 (13)	0.0073 (11)	0.0109 (11)	0.0151 (11)
C8	0.0507 (13)	0.0467 (13)	0.0597 (15)	0.0101 (10)	0.0175 (11)	0.0069 (11)
C9	0.0536 (13)	0.0364 (11)	0.0503 (13)	0.0112 (10)	0.0110 (10)	−0.0036 (9)
C10	0.0568 (13)	0.0338 (11)	0.0483 (13)	0.0064 (10)	0.0172 (10)	0.0061 (9)
C11	0.0333 (9)	0.0341 (10)	0.0347 (10)	0.0001 (7)	0.0126 (8)	−0.0014 (8)
C12	0.0426 (11)	0.0384 (11)	0.0377 (10)	−0.0048 (8)	0.0181 (9)	0.0008 (8)
C13	0.0442 (11)	0.0393 (11)	0.0367 (10)	−0.0024 (9)	0.0156 (9)	0.0035 (8)
C14	0.0711 (18)	0.0509 (14)	0.087 (2)	0.0061 (13)	0.0467 (16)	0.0243 (14)
C15	0.0783 (19)	0.0411 (13)	0.0668 (17)	0.0022 (12)	0.0244 (14)	0.0167 (12)
C16	0.110 (2)	0.0410 (13)	0.0704 (18)	0.0182 (15)	0.0463 (18)	0.0074 (12)
N1	0.0407 (9)	0.0392 (9)	0.0444 (10)	0.0059 (7)	0.0190 (8)	0.0051 (8)
N3	0.0495 (10)	0.0334 (9)	0.0468 (10)	0.0048 (7)	0.0231 (8)	0.0056 (8)
O1	0.0610 (10)	0.0554 (10)	0.0484 (9)	0.0130 (8)	0.0314 (8)	0.0036 (8)
O2	0.0557 (9)	0.0468 (9)	0.0438 (8)	0.0104 (7)	0.0234 (7)	0.0034 (7)
O3	0.0748 (12)	0.0491 (10)	0.0827 (13)	0.0055 (9)	0.0581 (11)	0.0093 (9)
O4	0.0855 (13)	0.0411 (9)	0.0653 (11)	0.0094 (9)	0.0492 (10)	0.0093 (8)
S1	0.0430 (3)	0.0376 (3)	0.0552 (3)	0.0064 (2)	0.0250 (2)	−0.0036 (2)
S2	0.0493 (3)	0.0451 (3)	0.0551 (4)	0.0086 (2)	0.0279 (3)	−0.0030 (2)
N2	0.0361 (8)	0.0318 (8)	0.0381 (9)	0.0022 (7)	0.0175 (7)	−0.0006 (7)
N4	0.0392 (9)	0.0326 (8)	0.0432 (9)	0.0019 (7)	0.0226 (8)	0.0021 (7)

Geometric parameters (Å, º) top

C1—C2	1.344 (3)	C9—S2	1.719 (3)
C1—S1	1.721 (3)	C9—H9	0.9300
C1—H1	0.9300	C10—N3	1.383 (3)
C2—N1	1.381 (3)	C10—H10	0.9300
C2—H2	0.9300	C11—N3	1.305 (2)
C3—N1	1.306 (3)	C11—N4	1.383 (3)
C3—N2	1.377 (3)	C11—S2	1.7252 (19)
C3—S1	1.7308 (18)	C12—O3	1.226 (3)
C4—O1	1.224 (2)	C12—N4	1.362 (2)
C4—N2	1.372 (3)	C12—C13	1.458 (3)
C4—C5	1.454 (3)	C13—C14	1.342 (3)
C5—C6	1.347 (3)	C13—O4	1.352 (3)
C5—O2	1.367 (2)	C14—C15	1.403 (4)
C6—C7	1.409 (4)	C14—H14	0.9300
C6—H6	0.9300	C15—C16	1.318 (4)
C7—C8	1.337 (4)	C15—H15	0.9300
C7—H7	0.9300	C16—O4	1.362 (3)
C8—O2	1.360 (3)	C16—H16	0.9300
C8—H8	0.9300	N2—H2A	0.81 (2)
C9—C10	1.339 (3)	N4—H4	0.80 (3)

C2—C1—S1	110.64 (17)	N3—C11—N4	121.20 (17)
C2—C1—H1	124.7	N3—C11—S2	115.77 (15)
S1—C1—H1	124.7	N4—C11—S2	123.03 (14)
C1—C2—N1	115.6 (2)	O3—C12—N4	121.7 (2)
C1—C2—H2	122.2	O3—C12—C13	120.40 (19)
N1—C2—H2	122.2	N4—C12—C13	117.86 (18)
N1—C3—N2	121.58 (17)	C14—C13—O4	109.5 (2)
N1—C3—S1	115.13 (15)	C14—C13—C12	130.7 (2)
N2—C3—S1	123.28 (14)	O4—C13—C12	119.70 (18)
O1—C4—N2	121.9 (2)	C13—C14—C15	107.3 (2)
O1—C4—C5	121.62 (19)	C13—C14—H14	126.4
N2—C4—C5	116.43 (17)	C15—C14—H14	126.4
C6—C5—O2	109.72 (19)	C16—C15—C14	106.0 (2)
C6—C5—C4	130.9 (2)	C16—C15—H15	127.0
O2—C5—C4	119.35 (17)	C14—C15—H15	127.0
C5—C6—C7	106.7 (2)	C15—C16—O4	111.2 (2)
C5—C6—H6	126.7	C15—C16—H16	124.4
C7—C6—H6	126.7	O4—C16—H16	124.4
C8—C7—C6	106.9 (2)	C3—N1—C2	110.11 (18)
C8—C7—H7	126.6	C11—N3—C10	109.25 (18)
C6—C7—H7	126.6	C8—O2—C5	106.43 (17)
C7—C8—O2	110.3 (2)	C13—O4—C16	105.90 (19)
C7—C8—H8	124.8	C1—S1—C3	88.55 (10)
O2—C8—H8	124.8	C9—S2—C11	88.36 (10)
C10—C9—S2	110.59 (17)	C4—N2—C3	123.13 (17)
C10—C9—H9	124.7	C4—N2—H2A	120.5 (17)
S2—C9—H9	124.7	C3—N2—H2A	116.3 (17)
C9—C10—N3	116.0 (2)	C12—N4—C11	122.93 (17)
C9—C10—H10	122.0	C12—N4—H4	121.6 (18)
N3—C10—H10	122.0	C11—N4—H4	115.4 (18)

S1—C1—C2—N1	0.0 (3)	S2—C11—N3—C10	−0.5 (2)
O1—C4—C5—C6	−5.9 (4)	C9—C10—N3—C11	0.3 (3)
N2—C4—C5—C6	174.3 (2)	C7—C8—O2—C5	−0.2 (3)
O1—C4—C5—O2	173.91 (19)	C6—C5—O2—C8	0.1 (3)
N2—C4—C5—O2	−5.9 (3)	C4—C5—O2—C8	−179.74 (19)
O2—C5—C6—C7	0.0 (3)	C14—C13—O4—C16	−0.4 (3)
C4—C5—C6—C7	179.8 (2)	C12—C13—O4—C16	176.9 (2)
C5—C6—C7—C8	−0.1 (3)	C15—C16—O4—C13	0.0 (4)
C6—C7—C8—O2	0.2 (3)	C2—C1—S1—C3	−0.3 (2)
S2—C9—C10—N3	0.0 (3)	N1—C3—S1—C1	0.56 (17)
O3—C12—C13—C14	−2.0 (4)	N2—C3—S1—C1	−178.42 (18)
N4—C12—C13—C14	176.5 (3)	C10—C9—S2—C11	−0.25 (19)
O3—C12—C13—O4	−178.6 (2)	N3—C11—S2—C9	0.47 (18)
N4—C12—C13—O4	−0.1 (3)	N4—C11—S2—C9	−179.10 (19)
O4—C13—C14—C15	0.6 (3)	O1—C4—N2—C3	−2.8 (3)
C12—C13—C14—C15	−176.3 (2)	C5—C4—N2—C3	176.97 (18)
C13—C14—C15—C16	−0.6 (4)	N1—C3—N2—C4	179.55 (19)
C14—C15—C16—O4	0.4 (4)	S1—C3—N2—C4	−1.5 (3)
N2—C3—N1—C2	178.33 (19)	O3—C12—N4—C11	2.3 (3)
S1—C3—N1—C2	−0.7 (2)	C13—C12—N4—C11	−176.26 (19)
C1—C2—N1—C3	0.4 (3)	N3—C11—N4—C12	175.2 (2)
N4—C11—N3—C10	179.04 (19)	S2—C11—N4—C12	−5.2 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C8—H8···O3ⁱ	0.93	2.42	3.301 (3)	159
N2—H2A···N3	0.81 (2)	2.23 (3)	3.023 (2)	164 (2)
N4—H4···N1	0.80 (3)	2.14 (3)	2.927 (2)	168 (2)

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

Dihedral angles (°) between planes P1, P2 and P3 top

See Fig. 2 for definitions of the planes.

Molecule	P1–P2	P2–P3	P1–P3
A	4.44	5.96	9.04
B	3.86	4.12	6.64

Geometric details (Å, °) of noncovalent interactions for 1 top

Cg1 is the centroid of the S1/C1/C2/N1/C3 ring, Cg2 is the centroid of the O2/C5/C6/C7/C8 ring, Cg3 is the centroid of the S2/C9/C10/N3/C11 ring and Cg4 is the centroid of the O4/C13–C16 ring. α is the dihedral angle between planes CgI and CgJ, β is the angle between the CgI–CgJ vector and normal to plane I and γ is the angle between the CgI–CgJ vector and normal to plane J.

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···O2	0.81 (2)	2.41	2.738 (3)	106
N4—H4···O4	0.80 (3)	2.47	2.763 (3)	103
N2—H2A···N3	0.81 (2)	2.23	3.023 (3)	164
N4—H4···N1	0.80 (3)	2.14	2.926 (3)	168
C8—H8···O3ⁱ	0.93	2.42	3.300 (3)	159

X—H···Cg	X—H	H···Cg	X···Cg	X—H···Cg
C7—H7···Cg1ⁱⁱ	0.93	2.86	3.621 (3)	140

Cg···Cg	Cg···Cg	α	β	γ
Cg1···Cg2ⁱⁱⁱ	3.782 (3)	9	15.7	24.2
Cg2···Cg1ⁱⁱⁱ	3.782 (3)	9	24.2	15.7
Cg3···Cg4^iv	3.890 (4)	7	22.7	16.3
Cg4···Cg3^iv	3.890 (4)	7	16.3	22.7

Selected geometrical parameters (Å, °) top

A		B
C4═O1	1.224 (2)	C12═O3	1.226 (3)
C4—N2	1.372 (3)	C12—N4	1.362 (2)
N2—C3	1.377 (3)	N4—C11	1.383 (3)
C4—C5	1.454 (3)	C12—C13	1.458 (3)
C3—S1	1.731 (2)	C11—S2	1.725 (2)
C1—S1	1.721 (3)	C9—S1	1.719 (3)

N1—C3—N2—C4	179.6 (2)	N3—C11—N4—C12	175.2 (2)
C3—N2—C4—C5	176.9 (2)	C11—N4-C12—C13	-176.3 (2)
N2—C4—C5—C6	174.3 (2)	N4—C12—–C13—C14	176.5 (3)

Electron delocalization and second-order interaction energies top

Donor (i)	Acceptor (j)	E(2) (kcal mol^-1)	E_j - E_i (a.u.)	F_ij (a.u.)
π(C3—N1)	π*(C1—C2)	18.97	0.35	0.075
π(C5—C6)	π*(C4—O1)	19.69	0.29	0.070
π(C5—C6)	π*(C7—C8)	15.74	0.29	0.061
π(C7—C8)	π*(C5—C6)	16.66	0.30	0.066
n1(N1)	σ*(C3—S1)	15.79	0.55	0.084
n2(O1)	σ*(C4—C5)	18.57	0.69	0.104
n2(O1)	σ*(C4—N2)	24.89	0.69	0.119
n2(O2)	π*(C5—C6)	25.36	0.37	0.087
n2(O2)	π*(C7—C8)	26.89	0.36	0.089
n2(S1)	π*(C1—C2)	19.28	0.26	0.066
n2(S1)	π*(C3—N1)	30.93	0.24	0.077
n1(N2)	π*(C3—N1)	42.74	0.27	0.098
n1(N2)	π*(C4—O1)	59.66	0.28	0.116

Thermodynamic properties of 1 at different temperatures top

Temperature (K)	Enthalpy (kcal mol^-1)	Entropy (cal mol^-1 K)	Heat capacity (cal mol^-1 K)
100	1.317	74.019	17.003
150	2.364	82.618	21.891
200	3.745	90.256	27.646
250	5.376	97.539	33.939
300	7.321	104.651	40.266
350	9.580	111.622	46.282
400	12.153	118.434	51.801
450	14.977	125.061	56.754
500	17.980	131.482	61.147

The minimum inhibition concentrations (MIC's) of the tested molecules top

`NT' denotes not tested.

Sample	Minimum inhibition concentration (µg ml^-1)
	Gram-staining-positive			Gram-staining-negative			Fungi
B. subtilis	S. aureus	E. faecalis	E. coli	K. pneumoniae	P. aeruginosa	A. niger	C. albicans
N-(Thiazol-2-yl)furan-2-carboxamide	500	500	500	1000	750	1000	1000	1000
Amoxicillin	<2	>1000	>1000	32	>1000	>1000	-	-
Tetracycline	<2	8	8	<2	8	4	-	-
Ketoconazole	-	-	-	-	-	-	1	2

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Format		BIBTeX
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		Medline
		CIF
		SGML
		Text
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Experimental and theoretical investigations on a furan-2-carboxamide-bearing thia­zole: synthesis, mol­ecular characterization by IR/NMR/XRD, electronic characterization by DFT, Hirshfeld surface analysis and biological activity

Supporting information

Experimental and theoretical investigations on a furan-2-carboxamide-bearing thiazole: synthesis, molecular characterization by IR/NMR/XRD, electronic characterization by DFT, Hirshfeld surface analysis and biological activity