Thiocyanate Derivatives Research Articles

Photoredox-catalyzed C–C bond cleavage of cyclopropanes for the formation of C(sp3)–heteroatom bonds

Sterically congested C–O and C–N bonds are ubiquitous in natural products, pharmaceuticals, and bioactive compounds. However, the development of a general method for the efficient construction of those sterically demanding covalent bonds still remains a formidable challenge. Herein, a photoredox-driven ring-opening C(sp3)–heteroatom bond formation of arylcyclopropanes is presented, which enables the construction of structurally diversified while sterically congested dialkyl ether, alkyl ester, alcohol, amine, chloride/fluoride, azide and also thiocyanate derivatives. The selective single electron oxidation of aryl motif associated with the thermodynamic driving force from ring strain-release is the key for this transformation. By this synergistic activation mode, C–C bond cleavage of otherwise inert cyclopropane framework is successfully unlocked. Further mechanistic and computational studies disclose a complete stereoinversion upon nucleophilic attack, thus proving a concerted SN2-type ring-opening functionalization manifold, while the regioselectivity is subjected to an orbital control scenario.

Experimental and computational tuning of metalla-N-heterocyclic carbenes at palladium(II) and platinum(II) centers.

Palladium(II) and platinum(II) complexes featuring metalla-N-heterocyclic carbenes (7-12) were synthesised via metal-mediated coupling between equimolar cis-[MCl2(CNR)2] (R = 2,6-Me2C6H3 (Xyl), 2,4,6-Me3C6H3 (Mes)) and 2-aminopyridine or 2-aminopyrazine. Thiocyanate complexes 13-18 with two thiocyanate ligands were obtained through the ligand exchange in the parent compounds 7-12 with NH4CNS in acetone/CH2Cl2. Complexes 7-18 were isolated and characterised by HRESI+-MS, IR, 1H and 13C{1H} NMR spectroscopy and single-crystal X-ray diffraction (in the case of 11, 16, and 18). The UV-vis properties of 7-18 and the electrochemical properties of 7-12 were also evaluated. To study the electronic structure and bonding nature in the new compounds, the quantum theory of atoms in molecules (QTAIM) and Mayer bond order analysis together with the extended transition state with the natural orbitals for chemical valence (ETS-NOCV) method, were used. X-ray diffraction studies and theoretical considerations indicate that the thiocyanate derivatives 16 and 18 form supramolecular dimers by two symmetrical pairs M1⋯C5 and S1⋯C2 with short intermolecular contacts between an electron-rich MII-center and thiocyanate ligand on the one side and the electron-poor π-system of an azaheterocyclic ring on the other side. Representative carbenes 8, 11 and 12 were evaluated as photocatalysts for the hydrosilylation of diphenylacetylene with triethylsilane giving 1,2-(diphenylvinyl)triethylsilane in 98% yield under visible light irradiation (blue light, 445 nm).

Synthetic and Mechanistic Studies on 2,3-Dihydrobenzo[b][1,4]-oxaselenines Formation from Selenocyanates

An expedient preparation of selenium-containing hetero­cycles via an m-chloroperbenzoic acid-mediated seleno-annulation starting from selenocyanate derivatives is described. In spite of its significance, this cyclization reaction is virtually understudied not only from the point of view of its scope, but also from the mechanistic aspects associated to this remarkable transformation. In this sense, several selenocyanate and thiocyanate derivatives bearing an aromatic ring were evaluated as substrates under different reaction conditions of this interesting cyclization yielding important insights on its scope as well as relevant information on the reaction mechanism.

C4‐Selective Synthesis of Vinyl Thiocyanates and Selenocyanates Through 3,4‐Dihalo‐2(5H)‐furanones

In the absence of a metal catalyst and under the promotion of sodium bicarbonate, an eco‐friendly and practical protocol for the synthesis of vinyl thiocyanate derivatives through the reaction of 3,4‐dihalo‐2(5H)‐furanones with KSCN at room temperature has been developed. This method has a broad substrate scope and is suitable for gram‐scale synthesis (up to 5 g). Importantly, it can also be used to synthesize vinyl selenocyanate derivatives.

Chiral and Racemic Spin Crossover Polymorphs in a Family of Mononuclear Iron(II) Compounds.

Understanding the origin of cooperativity and the equilibrium temperature of transition (T1/2) displayed by the spin-crossover (SCO) compounds as well as controlling these parameters are of paramount importance for future applications. For this task, the occurrence of polymorphism, presented by a number of SCO complexes, may provide deep insight into the influence of the supramolecular organization on the SCO behavior. In this context, herein we present a novel family of mononuclear octahedral FeII complexes with formula cis-[Fe(bqen)(NCX)2], where bqen is the chelating tetradentate ligand N,N'-bis(8-quinolyl)ethane-1,2-diamine and X = S, Se. Depending on the preparation method, these compounds crystallize in either the orthorhombic or the trigonal symmetry systems. While the orthorhombic phase is composed of a racemic mixture of mononuclear complexes (polymorph I), the trigonal phase contains only one of the two possible enantiomers (Λ or Δ), thereby generating a chiral crystal (polymorph II). The four derivatives undergo SCO behavior with well-differentiated T1/2 values occurring in the interval 90-233 K. On one hand, T1/2 is about 110 K (polymorph I) and 87 K (polymorph II) higher for the selenocyanate derivatives in comparison to those for their thiocyanate counterparts. These differences in T1/2 are ascribed not only to the higher ligand field induced by the selenocyanate anion but also to a remarkable difference in the structural reorganization of the [FeN6] coordination core upon SCO. Likewise, the higher cooperativity observed for the thiocyanate derivatives seems to be related to their stronger intermolecular interactions within the crystal. On the other hand, T1/2 is about 53 K (thiocyanate) and 29 K (selenocyanate) higher for the trigonal polymorph II in comparison to those for the orthorhombic polymorph I. These differences, and the small changes observed in cooperativity, stem from the slightly different hetero- and homochiral crystal packing generated by the cis-[Fe(bqen)(NCX)2] molecules, which determines subtle adaptations in the intermolecular contacts and the FeII coordination core.

Silver‐Catalyzed Regio‐ and Stereoselective Thiocyanation of Haloalkynes: Access to (Z)‐Vinyl Thiocyanates

AbstractA regio‐ and stereoselective method for the preparation of (Z)‐vinyl thiocyanate derivatives by silver‐catalyzed thiocyanation of haloalkynes is reported. This method features practical, free of ligand, broad substrate scope, excellent stereoselectivity and gram‐scale synthesis. Significantly, the halogen atom of haloalkynes is retained, which allows the synthesis of 2,5‐diphenylthiophene, thiazol‐2‐amine and trifluoromethyl sulfides derivatives via simple transformation.magnified image

Chalcogen containing heterocyclic scaffolds: New hybrids with antitumoral activity

In this work, 27 novel hybrid derivatives containing diverse substituents with chalcogen atoms (selenium or sulfur) and several active heterocyclic scaffolds have been synthesized. Compounds were tested against two human cancer cells lines (MCF7 and PC-3) and a normal human mammary epithelial cell line (184B5) in order to determine their activity and selectivity against malignant cells. Ten compounds showed GI50 values below 10 μM in at least one of the cancer cell lines and six of them exhibited a selectivity index higher than 9. In general, selenium-containing compounds were more active than their corresponding sulfur analogs but we found some thiocyanate derivatives with comparable or higher activity and selectivity. Among the different substituents, the seleno- and thio-cyanate groups showed the most promising results. On the basis of their potent activity and high selectivity index, compounds 7e and 8f (containing a thiocyanate and a selenocyanate group, respectively) were selected for further biological evaluation. Both the compounds induced caspase-dependent cell death and cell cycle arrest in G2/M phase. In addition, these compounds do not violate any of the Lipinski's Rule of Five and thus possess good potential to become drugs, compound 7e being particularly promising.

Synthesis of alkyl thiocyanates from alcohols using a polymer-supported thiocyanate ion promoted by cyanuric chloride/dimethylformamide

A convenient procedure for one-pot conversion of alcohols into the corresponding alkyl thiocyanates in the presence of cross-linked poly (N-propyl-4-vinylpyridinium) thiocyanate ion [P4-VP]Pr-SCN, promoted by cyanuric chloride/dimethylformamide, is described. Various alcohols were converted to their corresponding alkyl thiocyanates and it was observed that substituted benzyl alcohol with electron-withdrawing or electron-donating groups were transformed into the corresponding benzyl thiocyanate derivatives in high to excellent yields in a short reaction time but, sterically hindered alcohols produced the corresponding thiocyanates in very low yields.

Determination of thiocyanate in saliva by headspace gas chromatography-mass spectrometry, following a single-step aqueous derivatization with triethyloxonium tetrafluoroborate

A novel method for the determination of salivary thiocyanate is presented. Thiocyanate was converted into ethyl thiocyanate by single-step aqueous derivatization based on triethyloxonium tetrafluoroborate and measured by gas chromatography-mass spectrometry (15min runtime). The ethyl thiocyanate derivative is volatile and can be sampled from the headspace. The derivatization chemistry proposed allows for separation of the analyte from saliva matrix whose introduction in the measurement system is avoided. Quantitation of the analyte was obtained by isotope dilution, employing a 13C-enriched thiocyanate as internal standard. Technical details and fundamental aspects of derivatization chemistry and calibration strategy are presented.The method was validated by comparison with a standard method based on ion chromatography. The two independent methodologies produced results in agreement within 3%. Also a three level spike recovery test was carried out for validation purpose and quantitative recoveries were attained. The method is fast, simple, safe, and sensitive. Measurement of a 1mL volume 50ng/g of thiocyanate standard produced a signal-to-noise ratio of 250 for the analytical peak. This method is therefore suitable for ultra-trace determination of thiocyanate (low part-per-billion range). For the application described the full detection potential of the method was not required and the sample preparation presented has been designed for quantitation of saliva samples containing 1–400μg/g of thiocyanate with a combined standard uncertainty of 2% relative for saliva samples containing 25μg/g of thiocyanate. This method was applied for the determination of thiocyanate in human saliva samples.

Complexes of Copper(I) Thiocyanate with Monodentate Phosphine and Pyridine Ligands and the P(,N)‐Donor Diphenyl(2‐pyridyl)phosphine

AbstractCopper(I) thiocyanate derivatives were prepared by the reaction of CuNCS with pyridine (py) and tertiary monophosphine ligands [PR3 in general; in detail: PPh3, triphenylphosphine, P(4‐FPh)3, tris(4‐fluorophenyl)phosphine)], as well as the potentially bidentate ligand diphenyl(2‐pyridyl)phosphine (PPh2py). Mechanochemical methods were used in some cases to investigate stoichieometries that were not easily accessible by conventional solution syntheses. Three forms of the resulting adducts of CuNCS/PR3/py‐base (1:3–n:n) stoichiometry―all containing four‐coordinate copper(I) atoms and monodentate N‐thiocyanate groups―were confirmed crystallographically. Mononuclear arrays are defined for [(PPh2py)3–n(py)nCuNCS], n = 0, 1, 2, the monodentate thiocyanate being N‐coordinated in all; two polymorphs are observed for the n = 2 complex, both crystallizing in monoclinic P21 (Z = 2) cells with similar cell dimensions, but with aromatic components eclipsed about the Cu–P bond in the PPh3 complex, and staggered in the PPh2py complex. Bridging thiocyanate groups are found in the 1:1:1 CuNCS/PPh2py/2‐methylpyridine (mpy) and P(4‐FPh)3/mpy complexes, wherein centrosymmetric dimers with eight‐membered central rings are obtained: [(R3P)(mpy)Cu(NCS)2Cu(PR3)(mpy)], as is also the case in the parent 1:2 CuNCS/PPh2py adduct [(pyPh2P)2Cu(NCS)2Cu(PPh2py)2]. For the 1:1:1 CuNCS/P(4‐FPh)3/py and PPh3/Brmpy (Brmpy = 3‐bromo‐4‐methylpyridine) adducts, and, likely, CuNCS/PPh2py/py (1:1:1), single‐stranded polymers of the form [···Cu(NCS)(PR3)(py‐base)(Cu)···](∞|∞) with linearly bridging NCS ligands were obtained. Some derivatives, representative of all forms, display medium to strong green to blue luminescence when excited with radiation at 365 nm. The 31P CPMAS NMR spectroscopic data clearly differentiate the inequivalent phosphorus positions within each system, showing a wide range of 1J(31P,63/65Cu) values ranging from 965 Hz for [Cu(NCS)(PPh2py)3] to 1540 Hz for dimeric [(4‐FPh)3P(mpy)Cu(NCS)2Cu(P(4‐FPh)3)(mpy)], reflecting the large variations in the Cu–P bond length.

REGIOSELECTIVE AND FACILE OXIDATIVE THIOCYANATION OF ANILINES AND INDOLES WITH TRANS-3,5‐DIHYDROPEROXY‐3,5‐DIMETHYL‐1,2‐DIOXOLANE

Oxidative potential of trans‐3,5‐dihydroperoxy‐3,5‐dimethyl‐1,2‐dioxolane (DHPODMDO) has been explored in the facile thiocyanation of anilines and indoles through the efficient and in situ generation of SCN+ ion from sodium thiocyanate. The reactions proceed with regioselectivity under mild conditions at room temperature to afford the respective thiocyanate derivatives in excellent yields and low reaction times.

An Efficient One-Pot Synthesis of bis-1-(aroyl)-3-(aryl)thiourea

A three-component and one-pot reaction between 2,6-diaminopyridine or 1,2-diaminobenzene and ammonium thiocyanate with the subsequent addition of an aroyl chloride afforded the bis-1-(aroyl)-3-(aryl)thiourea in excellent yields. It was important to make the thiocyanate derivatives first and then to use those to prepare the thiourea derivatives.

Rearrangements of Acyl, Thioacyl, and Imidoyl (Thio)cyanates to Iso(thio)cyanates, Acyl Iso(thio)cyanates to (Thio)acyl Isocyanates, and Imidoyl Iso(thio)cyanates to (Thio)acyl Carbodiimides, RCX-YCN ⇌ RCX-NCY ⇌ RCY-NCX ⇌ RCY-XCN (X and Y = O, S, NR′)

Two types of rearrangements have been investigated computationally at the B3LYP/6-311+G(d,p) level. The activation barriers for rearrangement of acyl thiocyanates RCO-SCN to the corresponding isothiocyanates RCO-NCS are 30-31 kcal/mol in agreement with the observation that the thiocyanates are in some cases isolable albeit very sensitive compounds. Alkoxycarbonyl-, (alkylthio)carbonyl- and carbamoyl thiocyanates are isolable and have higher calculated barriers (ca. 40 kcal/mol) toward rearrangement to isothiocyanates, whereas all thioacyl thiocyanate derivatives are rather unstable compounds with barriers in the range 20-30 kcal/mol for rearrangement to the isothiocyanates. Acyl-, alkoxycarbonyl-, and carbamoyl cyanates R-CO-OCN are predicted to be in some cases isolable compounds with barriers up to ca. 40 kcal/mol for rearrangement to the isocyanates RCO-NCO. All of the rearrangements of this type involve the HOMO of a nearly linear (thio)cyanate anion and the LUMO of the acyl cation, in particular the acyl C═X π* orbital. The second type of rearrangement involves 1,3-shifts of the groups R attached to the (thio)acyl groups, that is, acyl isothiocyanate-thioacyl isocyanate and imidoyl isothiocyanate-thioacyl carbodiimide rearrangements. These reactions involve four-membered cyclic, zwitterionic transition states facilitated by lone pair-LUMO interactions between the migrating R group and the neighboring iso(thio)cyanate function. Combination of the two rearrangements leads to the general reaction scheme RCX-YCN ⇌ RCX-NCY ⇌ RCY-NCX ⇌ RCY-XCN (X and Y = O, S, NR').

ChemInform Abstract: Allylic Nitroxyl Spin Label Reagents.

2,5-Dihydro-3-hydroxymethyl-2,2,5,5-tetramethyl-1H-pyrrol-1-yloxy radical is used to prepare new allylic spin labels: thiocyanate, tributylstannane, thiourea, dithiocarbonate, disulfide and diselenide derivatives, with or without allylic rearrangements

ChemInform Abstract: Design and Synthesis of Aryloxyethyl Thiocyanate Derivatives as Potent Inhibitors of Trypanosoma cruzi Proliferation.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Anodic thiocyanation of mono- and disubstituted aromatic compounds

The in situ and environmentally friendly thiocyanation (no use of toxic oxidizing agents) electrochemical thiocyanation of aromatic compounds involving various derivatives of anisole and aniline to afford aromatic thiocyanates have been studied in organic acidic media. The initial electrochemical step involves anodic oxidation of thiocyanate anion to its radical (SCN), followed by dimerization to thiocyanogen (SCN) 2. The latter is polarized by the acidic solvent and attacks the aromatic nucleus of the substrate to afford the corresponding thiocyanate derivative. The sole thiocyanate products obtained in each case shows high regio-selectivity (no ortho isomer was observed) for the monosubstituted aromatics and high isomer-selectivity (no isothiocyanate isomer was detected) for both mono- and disubstituted aromatics.

Organometallic Trinuclear Niobium Cluster Complex in Aqueous Solution: Synthesis and Characterization of Niobium Complexes Containing Nb3(μ-η2:η2(⊥)-NCCH3)(μ2-O)36+ Cluster Core

The synthesis and characterization of an organometallic trinuclear oxo-bridged niobium cluster complex with perpendicularly coordinated mu(3)-eta(2):eta(2)( perpendicular)-acetonitrile ligand in aqueous solution is reported. Reaction of NbCl(5) in acetonitrile with aluminum under argon followed by reaction with aqueous hydrochloric acid affords, after suitable workup, the isolation of the organometallic [Nb(3)(mu-eta(2):eta(2)-NCCH(3))O(3)(H(2)O)(9)](6+) aqua ion by cation-exchange chromatography. The purple niobium aqua ion in 2 M HCl shows a small peak at 365 nm (epsilon approximately 511 M(-1) cm(-1) per Nb) and a broad peak at 565 nm (epsilon approximately 335 M(-1) cm(-1)) in the UV-visible region. It is electron paramagnetic resonance (EPR)-active (g = 1.98), but no hyperfine interaction with the (93)Nb nuclear spin (I = 9/2) was observed. The cyclic voltammogram of [Nb(3)(mu-eta(2):eta(2)-NCCH(3))O(3)(H(2)O)(9)](6+) in 4 M HCl on edge-plane pyrolytic graphite electrode at 50 mV s(-1) in the potential range -1.2 V to +1.1 V (vs SCE) exhibits three anodic peaks at -0.12, +0.53, and +0.85 V and a large cathodic peak at -0.91 V with a slight shoulder at about -0.8 V. The purple aqua ion reacted with potassium thiocyanate to give the green thiocyanate derivative, which was crystallized as ((CH(3))(3)NH)(3)[Nb(3)(mu-eta(2):eta(2)-NCCH(3))O(3)(NCS)(9)].2.5H(2)O (1) and subjected to X-ray structure analysis. Density-functional theory (DFT) calculations fully supported the structure of the cluster.

Formation of an oxathiolone compound from rutin in acidic mixture of saliva and buckwheat dough: Possibility of its occurrence in the stomach

Abstract Buckwheat is used for various foods in the world. The objective of the present study is the determination of the chemical structure of a product formed in the acidic mixture of buckwheat dough and saliva that contains both nitrite and thiocyanate. In the mixture, an oxathiolone derivative of rutin, 5,7-dihydroxy-2-(7-hydroxy-2-oxobenzo[d][1,3]oxathiol-4-yl)-4H-chromen-4-one-3-O-β-rutinoside, was found. This compound seemed to be formed by the hydrolysis of a 2′-thiocyanate derivative of rutin, which was produced by the reaction of thiocyanate with the o-quinone generated by nitrous acid-dependent oxidation of rutin. Importance of the formation of the oxathiolone compound is discussed in relation to scavenging of the toxic quinone in the stomach.

Simple and quick preparation of α-thiocyanate ketones in hydroalcoholic media. Access to 5-aryl-2-imino-1,3-oxathiolanes

A simple preparation on gram-scale of thiocyanate derivatives via nucleophilic substitution of halogenated compounds with SCN salts at high substrate concentrations in a few minutes and excellent yields was successfully accomplished in hydroalcoholic media. The obtained compounds were employed for the efficient synthesis of valuable 5-aryl-2-imino-1,3-oxathiolane derivatives (a one-pot approach is also presented).

Tryptophan residues are targets in hypothiocyanous acid-mediated protein oxidation

Myeloperoxidase, released by activated phagocytes, forms reactive oxidants by catalysing the reaction of halide and pseudo-halide ions with H(2)O(2). These oxidants have been linked to tissue damage in a range of inflammatory diseases. With physiological levels of halide and pseudo-halide ions, similar amounts of HOCl (hypochlorous acid) and HOSCN (hypothiocyanous acid) are produced by myeloperoxidase. Although the importance of HOSCN in initiating cellular damage via thiol oxidation is becoming increasingly recognized, there are limited data on the reactions of HOSCN with other targets. In the present study, the products of the reaction of HOSCN with proteins has been studied. With albumin, thiols are oxidized preferentially forming unstable sulfenyl thiocyanate derivatives, as evidenced by the reversible incorporation of (14)C from HOS(14)CN. On consumption of the HSA (human serum albumin) free thiol group, the formation of stable (14)C-containing products and oxidation of tryptophan residues are observed. Oxidation of tryptophan residues is observed on reaction of HOSCN with other proteins (including myoglobin, lysozyme and trypsin inhibitor), but not free tryptophan, or tryptophan-containing peptides. Peptide mass mapping studies with HOSCN-treated myoglobin, showed the addition of two oxygen atoms on either Trp(7) or Trp(14) with equimolar or less oxidant, and the addition of a further two oxygen atoms to the other tryptophan with higher oxidant concentrations (> or = 2-fold). Tryptophan oxidation was observed on treating myoglobin with HOSCN in the presence of glutathione and ascorbate. Thus tryptophan residues are likely to be favourable targets for the reaction in biological systems, and the oxidation products formed may be useful biomarkers of HOSCN-mediated protein oxidation.