Thiourea Unit Research Articles

1,4-Diphosphinines from Imidazole-2-thiones.

1,4-Diphosphinines that are fused to two thiourea units were synthesized from the corresponding tricyclic 1,4-dichloro-1,4-dihydro-1,4-diphosphinines, and their structures and spectroscopic features are described. Electrochemical studies revealed very low oxidation potentials, which are due to the effective π-interaction between the 1,4-diphosphinine ring and the orbitals of the two ylidic C=S bonds. In accordance with the low-lying LUMO, which is largely localized at the two phosphorus centers, dianion formation is strongly preferred. Despite the small HOMO-LUMO gap, which is in accordance with the red color of the title compounds, theoretical calculations suggest considerable aromaticity for the 1,4-diphosphinine ring.

Thiourea-Based Bifunctional Ionic Liquids as Highly Efficient Catalysts for the Cycloaddition of CO2 to Epoxides

A series of thiourea-based ionic liquids (TBILs) were developed as efficient catalysts for the synthesis of cyclic carbonates by the cycloaddition of CO2 with epoxides under metal-, cocatalyst- and solvent-free conditions. Different substituted groups including electron donating and withdrawing groups were introduced onto the para-position of the aromatic ring in cation of TBILs. The effect of the catalyst structures on the reaction activity was systematically investigated. Among the ionic liquids, TBIL3 with substituted OCH3 group showed the best performance with 99% propylene oxide conversion as well as 99% propylene carbonate selectivity under mild conditions (1.5 MPa, 130 °C and 3 h) without any co-solvent. It was demonstrated that two secondary amine groups of the thiourea unit could dually activate the epoxides and CO2 and have a synergetic effect with the halide anion.

SYNTHESIS AND CYCLIZATION OF SOME THIOSEMICARBAZIDE DERIVATIVES

The thiosemicarbazide 3 was obtained from reaction between hydrazine 2 and heteroallene 1. The condensed triazotriazole derivative 5 was obtained from the reaction of compound 3 with diethyl malonate. The cyclization of thiourea unit of compound 3 by heteroallene 1 furnished triazine 8. Benzoylation of compound 3 using benzoyl chloride 9 formed triazole derivative 11. Reaction of compound 3 and maleic anhydride 12 gave furothiadiazine 13. cyclohexanopyrimidinthione 16 was obtained as a result of cyclocondensation of cyclohexanone 14 with compound 3. Triazole 19 obtained from compound 3 and ammonium isothiocyanate 17 under thermal condition. Reaction of compound 3 with ethyl bromoacetate gave thiazole derivative 22. [2+3] cyclocondensation of acetyl acetone 23 and compound 3 provided pyrazole 25. Triazolotriazole 27 obtained from Formalin 26 and compound 3. Compound 3 suffers intramolecular base mediated cyclization affording triazole 28. Keeping compound 3 and propinaldehyde 29 under reflux provided triazolotriazole 31. Compound 3 oxidized by iodine to oxadiazole 32. Acylation of compound 3 by succinic acid formed triazolthione 34.

Synthesis, characterization, and in vitro evaluation and in silico molecular docking of thiourea derivatives incorporating 4-(trifluoromethyl)phenyl moiety

A series of acyl thiourea derivatives bearing 4-(trifluoromethyl)phenyl moiety (7 compounds) has been synthesized and characterized by FT-IR, 1H and 13C NMR spectroscopy and elemental analyses. The molecular structure of five compounds (2, 4, 5, 6 and 7) was determined by single crystal X-ray diffraction analysis. The crystal structures revealed that the carbonyl thiourea units in all determined compounds are mostly planar due in part to the formation of intramolecular NH⋯OC and CH⋯SC hydrogen bonds that form two S (6) rings. The intermolecular contacts of five crystal structures have been preformed based on the Hirshfeld surface and their associated 2D fingerprint plots. All the synthesized compounds were preliminarily screened for their in vitro anti-fungal activity. Especially, compounds 4, 5 and 6 showed a good anti-fungal activity for four different kinds of fungi. Furthermore, all prepared thiourea derivatives were screened for antioxidant potential activity by DPPH free radical scavenging and the excellent activity were found compounds 5 and 6 with the IC50 value of 191.75 μg/mL and 189.75 μg/mL, respectively. In silico molecular docking studies were performed to screen the thiourea derivatives against heat shock protein HSP90.

Understanding the conformational changes and molecular structure of furoyl thioureas upon substitution

1-Acyl thioureas [R1C(O)NHC(S)NR2R3] are shown to display conformational flexibility depending on the degree of substitution at the nitrogen atom. The conformational landscape and structural features for two closely related thioureas having R1=2-furoyl have been studied. The un-substituted 2-furoyl thiourea (I) and its dimethyl analogue, i.e. 1-(2-furoyl)-3,3-dimethyl thiourea (II), have been synthesized and fully characterized by spectroscopic (FT-IR, 1H and 13C NMR) and elemental analysis. According to single crystal X-ray diffraction analysis, compounds I and II crystallize in the monoclinic space group P21/c. In the compound I, the trans–cis geometry of the almost planar thiourea unit is stabilized by intramolecular NH⋯OC hydrogen bond between the H atom of the cis thioamide and the carbonyl O atom. In compound II, however, the acyl thiourea group is non-planar, in good agreement with the potential energy curve computed at the B3LYP/6-31+G(d,p) level of approximation. Centrosymmetric dimers generated by intermolecular NH⋯SC hydrogen bond forming R22(8) motif are present in the crystals. Intermolecular interactions have been rationalized in terms of topological partitions of the electron distributions and Hirshfeld surface analysis, which showed the occurrence of S⋯H, O⋯H and H⋯H contacts that display an important role to crystal packing stabilization of both thiourea derivatives.

Synthesis, structural and spectroscopic studies of 1-(2-FUROYL)-3-phenylthiourea: a theoretical and experimental approach

ABSTRACT The thiourea derivative 1-(2-Furoyl)-3-phenylthiourea (FPT) was synthesized and characterized by using spectroscopic (IR, Raman, UV–VIS, 1H and 13C NMR) and structural methods (powder X-ray diffraction data). The experimental measurements were complemented with quantum chemical calculations. FPT crystallizes in the monoclinic crystal system, space group P21/c, with cell parameters a = 4.7679(5) Å, b = 20.9704(2) Å, c = 12.5109(5) Å and β = 109.811(10)°, V = 1176.87(3) Å3. In the crystal structure, the thiourea group makes dihedral angle of 43.8(5)° with the furoyl group, whereas the benzene ring is inclined by 24.3(4)°. The anti-syn geometry of the thiourea unit is stabilized by intramolecular N–H … O hydrogen bond between the H atom of the syn thioamide and the carbonyl O atom. In the crystal structure, molecules of FPT are packed through N–H···S, C–H···O and C–H···C hydrogen bonds, and a π–π interaction with offset arrangement. Hirshfeld surface analysis was performed in order to evaluate and quantify intermolecular interactions. The Hirshfeld surface analysis indicated that the H···H interactions comprise the majority of interactions. Shape index and curvedness clearly indicate π–π interactions in the compound FPT.

Solid‐Phase Synthesis of Hybrid Urea Oligomers Containing Conservative Thiourea Mutations

AbstractThe introduction of a thiourea unit at a selected position in the backbone of aliphatic N,N′‐linked urea foldamers can be used to locally modulate the secondary structure and physicochemical properties. To facilitate scanning the effect of thiourea introduction into biologically active oligourea helices, we have investigated the solid‐phase synthesis of oligoureas containing a single oxo‐to‐thioxo replacement in their sequence. Several suitably protected activated monomers were considered, and conditions for their coupling and deprotection were evaluated and compared. The synthesis of oligo(thio)ureas on TFA‐labile resins (i.e., Rink amide resin; TFA = trifluoroacetic acid) required careful optimization, and the choice of N‐Fmoc‐aminoalkyl isothiocyanates (Fmoc = fluorenylmethoxycarbonyl) as monomers for thiourea‐bond formation was found to be critical.

Synthesis and properties of three novel rhodamine-based fluorescent sensors for Hg2+

Abstract Three novel rhodamine-based Hg2+ fluorescent sensors were designed and synthesized. The sensors could work in semi-aqueous solutions with nearly neutral pH and showed high selectivity and sensitivity to Hg2+ with remarkable fluorescence enhancement. For these three sensors, the linear working range broadened (0–80, 0–100 and 0–140 μmol/L, respectively) and the sensitivity increased (7.7, 15.5 and 17.6 folds of the fluorescence enhancement and 512, 66.2 and 37.6 ppb of the detection limit) with the rising of the thiourea-unit numbers. Furthermore the sensors exhibited excellent interference immunity to multiple environmentally and biologically relevant metal ions. Pond and tap water assay showed good practicability of the sensors. The number of the bound Hg2+ equaling to that of the thiourea units and the irreversible recognition process implied a new interaction way between Hg2+ and the sensor.

A dual-mode turn-on fluorescent BODIPY-based probe for visualization of mercury ions in living cells.

A novel turn-on fluorescent 8-amino BODIPY-based probe carrying a thiourea unit as the mercury ion recognition unit has been developed. Due to the cascade reaction processes, consecutive color changes reflecting the electronic absorption and emission responses were observed upon addition of increased concentrations of mercury(ii) ions. The likely sensing mechanism was proposed as mercury ion-promoted cyclization and subsequent hydrolysis. The probe displayed a selective response to mercury ions over other metal ions. Additionally, experiments with living Human Hepatoma SMMC-7721 cells to visualize intracellular mercury ions in biological systems were carried out with the probe.

Crystal structure of N-[(4-eth-oxy-phen-yl)carbamo-thio-yl]cyclo-hexa-ne-carboxamide.

The asymmetric unit of the title compound, C16H22N2O2S, contains two crystallographically independent mol­ecules (A and B). In mol­ecule A, the cyclo­hexane ring is disordered over two orientations [occupancy ratio 0.841 (10):0.159 (10)]. In each mol­ecule, the central carbonyl thio­urea unit is nearly planar (r.m.s. deviations for all non-H atoms of 0.034 Å in mol­ecule A and 0.094 Å in mol­ecule B). In both mol­ecules, the cyclo­hexane ring adopts a chair conformation. The mean plane of the cyclo­hexane ring makes dihedral angles of 35.8 (4) (mol­ecule A) and 20.7 (3)° (mol­ecule B) with that of the benzene ring. Each mol­ecule features an intra­molecular N—H⋯O hydrogen bond, which closes an S(6) ring motif. In the crystal, mol­ecules are linked via pairs of weak N—H⋯S inter­actions, forming inversion dimers with an R 2 2(8) ring motif for both mol­ecules. The crystal structure also features weak C—H⋯π ring inter­actions.

Two 1-(2-Furoyl)-3-phenylthiourea Derivatives: Synthesis, Characterization and Structural Study from X-ray Powder Diffraction Using Simulated Annealing

1-(2-furoyl)-3-p-cyanophenylthiourea (1) and 1-(2-furoyl)-3-o-fluorophenylthiourea (2) were synthesized by converting 2-furoyl chloride into 2-furoyl isothiocyanate and then condensing with the appropriated aniline derivatives. Both products were characterized by elemental analysis, Fourier transform infrared spectroscopy, Raman, 1H, 13C nuclear magnetic resonance and ab initio X-ray powder structure analysis. Compound 1 crystallizes in the monoclinic space group P21/n with unit cell dimensions a = 23.169(2) A, b = 11.353(2) A, c = 4.798(3) A, β = 90.30(2)°, V = 1,259.87(3) A3, Z = 4, R p = 4.62, and R wp = 7.86. Compound 2 crystallizes also in the monoclinic space group P21/n with unit cell dimensions a = 12.072(1) A, b = 20.801(2) A, c = 4.737(2) A, β = 93.34(2)°, V = 1,189.62(3) A3, Z = 4, R p = 3.95, and R wp = 7.06. The crystal structures have been determined from laboratory X-ray powder diffraction data using direct space global optimization strategy (simulated annealing) followed by the Rietveld refinement. The thiourea group makes a dihedral angle of 9.4(5)° and 33.5(4)° with the furoyl group in 1 and 2, respectively. In both compounds, the trans–cis geometry of the thiourea unit is stabilized by intramolecular N–H⋯O hydrogen bond between the H atom of the cis thioamide and the carbonyl O atom. In the crystal structure of compound 1, molecules are linked by intermolecular N–H⋯S bonds, forming one-dimensional chains along the c axis. For compound 2, only Van der Waals interactions are observed in the crystal structure, forming one-dimensional chains along the b axis. Crystal structure analysis from X-ray powder diffraction data and spectroscopic characterization of two 1-(2-furoyl)-3-phenylthiourea derivatives.

A one-pot multistep cyclization yielding thiadiazoloimidazole derivatives.

A versatile synthetic procedure is described to prepare the benzimidazole-fused 1,2,4-thiadiazoles 2a–c via a methanesulfonyl chloride initiated multistep cyclization involving the intramolecular reaction of an in-situ generated carbodiimide with a thiourea unit. The structure of the intricate heterocycle 2a was confirmed by single-crystal X-ray analysis and its mechanism of formation supported by DFT computations.

Optimization of the anti-cancer activity of phosphatidylinositol-3 kinase pathway inhibitor PITENIN-1: switching a thiourea with 1,2,3-triazole.

We previously reported encouraging in vitro and in vivoanti-cancer activity of N-((3-chloro-2-hydroxy-5-nitrophenyl)carbamothioyl)benzamide (termed PITENIN-1). In the current work, we describe the structure-activity relationship study of PIT-1 series, based on the replacement of central thiourea unit with a 1,2,3-triazole, which leads to increased liver microsomal stability, drug likeness and toxicity towards cancer cells.

1-{[(Z)-Cyclopentylidene]amino}-3-phenylthiourea

The sample of the title compound, C12H15N3S, chosen for study consisted of triclinic crystals twinned by a 180° rotation about the a axis. The five-membered ring adopts a twisted conformation. The dihedral angle between the phenyl ring and the mean plane of the thio­urea unit is 78.22 (8)°. In the crystal, molecules are linked via pairs of N—H⋯S hydrogen bonds forming inversion dimers.

Theoretical Mechanism Studies on the Enantioselectivity of aza-MBH-type Reaction of Nitroalkene to N-tosylimine Catalyzed by Thiourea-tertiary Amine

The enantioselective aza-Morita Baylis Hillman reaction of nitroalkene and N-tosylimine catalyzed by thiourea-tertiary amine has been investigated using density functional theory. Enantioselectivity is dominated by the cooperative effect of non-covalent and weak covalent interactions imposed by different units of catalyst. As Lewis base, the tertiary amine unit activates nitroalkene via weak covalent bond. The weak covalent interaction orients the reaction in a major path with smaller variations of this bond. The aromatic ring unit activates N-tosylimine via <TEX>${\pi}-{\pi}$</TEX> stacking. The non-covalent interaction selects the major path with smaller changes of the efficient packing areas. Thiourea unit donates more compact H-bonded network for species of the major path. The calculated ee value in xylene solution phase (97.6%) is much higher than that in N,N-Dimethylformamide (27.2%). Our conclusion is also supported by NBO analysis.

Design, synthesis and biological evaluation of di-substituted cinnamic hydroxamic acids bearing urea/thiourea unit as potent histone deacetylase inhibitors

A novel class of di-substituted cinnamic hydroxamic acid derivatives containing urea or thiourea unit was designed, synthesized and evaluated as HDAC inhibitors. All tested compounds demonstrated significant HDAC inhibitory activities and anti-proliferative effects against diverse human tumor cell lines. Among them, 7l exhibited most potent pan-HDAC inhibitory activity, with an IC50 value of 130nM. It also showed strong cellular inhibition against diverse cell lines including HCT-116, MCF-7, MDB-MB-435 and NCI-460, with GI50 values of 0.35, 0.22, 0.51 and 0.48μM, respectively.

1-(2-Chlorobenzoyl)-3-(pyrimidin-2-yl)thiourea

In the title compound, C12H9ClN4OS, the carbonyl group is at a cis position with respect to the thio­urea unit. The dihedral angle between the phenyl and pyrimidine ring is 16.49 (6)°. An intra­molecular N—H⋯N hydrogen bond stabilizes the mol­ec­ular conformation. In the crystal, N—H⋯N, C—H⋯O and C—H⋯S hydrogen bonds generate chains along the bc axis.

SAR, Cardiac Myocytes Protection Activity and 3D-QSAR Studies of Salubrinal and its Potent Derivatives

Salubrinal is a selective inhibitor of endoplasmic reticulum (ER) stress and affords remarkable protection to cardiomyocytes. By studying the structure-activity relationship (SAR) of salubrinal, it was found that modification of the quinoline ring terminus and thiourea unit could confer the compound PP1-24 with markedly enhanced cardioprotective activity (EC50 ≤ 0.3 μM) that is 50-fold more potent than salubrinal. Comparative molecular field analysis (CoMFA) was performed using the obtained biological data and resulted in a statistically significant CoMFA model with high predictive power (q2 = 0.741, r2 = 0.991).

SAR, Cardiac Myocytes Protection Activity and 3D-QSAR Studies of Salubrinal and its Potent Derivatives

Salubrinal is a selective inhibitor of endoplasmic reticulum (ER) stress and affords remarkable protection to cardiomyocytes. By studying the structure–activity relationship (SAR) of salubrinal, it was found that modification of the quinoline ring terminus and thiourea unit could confer the compound PP1-24 with markedly enhanced cardioprotective activity (EC50 ≤ 0.3 μM) that is 50-fold more potent than salubrinal. Comparative molecular field analysis (CoMFA) was performed using the obtained biological data and resulted in a statistically significant CoMFA model with high predictive power (q2 = 0.741, r2 = 0.991). Keywords: Cardiomyocytes protection, UPR, endoplasmic reticulum (ER) stress, eukaryotic translation initiation factor 2 subunit α (eIF2α) phosphorylation, PP1/GADD34 complex inhibitor, salubrinal, structure–activity relationships (SAR), MTT, CoMFA model, predicted abilities.

Coumarin-based chiral fluorescence sensor incorporating a thiourea unit for highly enantioselective recognition of N-Boc-protected proline

New coumarin-based chiral thiourea sensor 1 was found to be an enantioselective fluorescent chemosensor for N-Boc-protected proline. The chiral sensor shows lower background fluorescence, and higher fluorescence enhancement with 18 nm blue shifts. Job plot analysis result indicates that sensor 1 can form a 1 : 1 stoichiometric complex and it could be used as a fluorescence sensor for the determination of enantiomer composition of N-Boc-protected proline.