Copper-catalyzed tandem reactions of 2-halobenzenamines with isothiocyanates under ligand- and base-free conditions

A ligand-free copper-catalyzed reaction of 2-halobenzenamines with isothiocyanates has been developed for the synthesis of 2-aminobenzothiazoles. In the presence of CuBr and TBAB (tetra-n-butyl ammonium bromide, additive), a variety of 2-halobenzenamines underwent the reaction with isothiocyanates at 40 °C, affording 2-aminobenzothiazoles in moderate to excellent yields. It is noteworthy that the reaction is conducted under mild, relatively low catalyst loading, and ligand- and base-free conditions.     

Mesoionic 2-acylimino-1,3,4-thiadiazoles

Mesoionic 2-carbamoylimino-, 2-thiocarbamoylimino-, and 2-methacryloylmnno-1,3,4-thiadiazoles were obtained by reaction of α-alkylthioacylhydrazines with the appropriate acyl isothiocyanates. Mesoionic 1,3,4-thiadiazole-2-thione is also formed in the reaction with diethylthiocarbamoyl isothiocyanate.     

A versatile one-pot multicomponent synthesis of novel quinazolinon-2-yl-tetrasubstituted thiophenes

Here, we report a versatile multicomponent synthesis of novel quinazolinon-2-yl-tetrasubstituted thiophenes by a one-pot reaction using different alkyl-3-aminobutenoates, isothiocyanates and 2-halomethyl quinazolinones in good to excellent yields. The reaction probably proceeds by an intramolecular 5-exo-trig cyclisation.     

Atropisomeric carbohydrate imidazolidines: a novel class of nonbiaryl atropisomers

Stable axially chiral atropisomers have been prepared by reaction of 2-aminosugars with o,o′-disubstituted aryl isocyanates and isothiocyanates; these rotationally restricted heterobiaryls constitute a novel class of atropisomers for use in atroposelective reactions.     

Efficient one-pot synthesis of 1-alkoxy-2-arylaminoimidazolines from N-alkoxy-N-(2-aminoethyl)-2-nitrobenzenesulfonamides and arylisothiocyanates

A new synthetic approach towards 1-alkoxy-2-aminoimidazolines that uses N-alkoxy-N-(2-aminoethyl)-2-nitrobenzenesulfonamides as nucleophile reagents for the reaction with isothiocyanates is reported. Hence, the synthesis of 1-alkoxy-2-aminoimidazolines was performed in high yield with a one-pot procedure involving thiourea formation, nosyl group removal and spontaneous cyclization (42-77% overall yield).     

Solid-phase synthesis of 2-imidazolidinethiones via Mitsunobu reaction of N-(2-hydroxyethyl)thioureas

This letter reports the solid-phase synthesis of 2-imidazolidinethiones via the N-cyclization of N-(2-hydroxyethyl)thioureas using the Mitsunobu reaction in good yield and purity. This process employed the reductive amination of an ArgoGel-MB-CHO resin to anchor the aminoalcohols, followed by a reaction with isothiocyanates to give the resin-attached N-(2-hydroxyethyl)thioureas. Cleavage of the 2-imidazolidinethiones was performed with trifluoroacetic acid.     

Stereocontrolled synthesis of thiohydantoin spironucleosides from sugar spiroacetals

5-Epithiohydantocidin, N-alkyl and N-glycosylthiohydantoin spironucleosides are prepared from glycosylaminoesters and from furanoid and pyranoid methyl isothiocyanatoulosonates. The aminoesters and the isothiocyanates are obtained, in a stereocontrolled manner, from sugar spiroacetals through a high-yielding sequence involving ring opening with trimethyl azide, formation of an ester group, reduction of the azide, and, in the case of isothiocyanates, reaction with thiophosgene.     

Copper-catalyzed one-pot synthesis of 2-thioxo-2,3-dihydroquinazolin-4(1H)-ones from ortho-bromobenzamides and isothiocyanates

Copper-catalyzed tandem reaction of ortho-bromobenzamides and isothiocyanates is described, which provides an efficient and practical route for the synthesis of 2-thioxo-2,3-dihydroquinazolin-4(1H)-ones. The optimal condition involved the following parameters: CuI as precatalyst, Cs₂CO₃ as base, N,N′-dimethylethane-1,2-diamine as ligand, and toluene as solvent, with reaction temperature at 120 °C.     

Iodine-mediated direct synthesis of multifunctional 2-aminobenzimidazoles from N-substituted o-diaminoarenes and isothiocyanates

Multifunctional 2-aminobenzimidazoles were directly synthesized through sequential addition of N-substituted o-diaminoarenes to isothiocyanates, formation of carbodiimides via I₂-mediated oxidative desulfurization, and intramolecular cycloaddition. This efficient and eco-friendly synthetic process provides a facile access to diverse 2-aminobenzimidazole derivatives from readily accessible substrates under mild reaction conditions in a scalable fashion.     

Facile synthesis of 1-aminoisoquinolines via the tandem reactions of 2-alkynylbenzaldoximes with isothiocyanates

A new, concise, and efficient route for the synthesis of 1-aminoisoquinolines in good to excellent yields is described; this involves the reaction of 2-alkynylbenzaldoximes and isothiocyanates, which is catalyzed by silver triflate in dichloromethane, at room temperature. This transformation involves tandem 6-endo cyclization, [3+2] cycloaddition, and subsequent rearrangement. The simple operational protocol provides a cost-effective, diversity-oriented route to 1-aminoisoquinolines under neutral, mild conditions.     

Derivatives and reactions of glutacondialdehyde IV 1-substituted-3-formyl-2(1H)-pyridinethiones

The reaction of the glutacondialdehyde anion with alkyl and acyl isothiocyanates has been investigated. Whereas alkyl isothiocyanates give rise to 1-alkyl-3-formyl-2(1$\text{H}$)-pyridinethiones, $\text{O}$-acylated glutacondialdehyde derivatives are formed from acyl isothiocyanates in most cases. The reaction courses may be understood on the basis of the principle of hard and soft acids and bases.     

Chemical transformations of N-morpholinylacetic acid hydrazide and steric structure of its derivatives

The reaction of N-morpholinylacetic acid hydrazide with various isothiocyanates and potassium thiocyanate resulted in the corresponding potentially biologically active thiosemicarbazide derivatives. Potassium N′-(2-morpholin-4-ylacetyl)hydrazinocarbothioate was synthesized and involved into heterocyclization in acidic environment to yield cyclic 5-(morpholinomethyl)-1,3,4-thiadiazole-2-thione. The structure of the synthesized compounds was established by IR, ¹H NMR spectroscopy, mass spectrometry, and XRD analysis.     

A new efficient synthesis of isothiocyanates from amines using di-tert-butyl dicarbonate

Alkyl and aryl amines are converted smoothly to the corresponding isothiocyanates via the dithiocarbamates in good to excellent yields using di-tert-butyl dicarbonate (Boc₂O) and 1-3 mol % of DMAP or DABCO as catalyst. As most of the byproducts are volatile, the work-up involves simple evaporation of the reaction mixture.     

Novel approach towards 2-substituted aminobenzimidazoles on imidazolium ion tag under focused microwave irradiation

We have developed an efficient, parallel synthesis of 2-substituted aminobenzimidazoles via intramolecular ring closing reactions of imidazolium ion tag immobilized o-phenylenediamine with various isothiocyanates. The methodology is based on the attachment of 4-fluoro-3-nitro benzoic acid into the imidazolium ion tag, which enables the S_NAr reactions with different amines followed by neutral reduction to furnish o-phenylenediamines under microwave irradiation. The substituted isothiocyanates are reacted with o-phenylenediamines to form monothiourea, which is further activated by methyl iodide to undergo desulfurization in one pot manner. The ionic liquid bound 2-substituted aminobenzimidazoles were finally cleaved from the support with sodium methoxide to generate target compounds in good yields and high purities with two points of structural diversity. This synthetic protocol has promising features of extremely short reaction time, operational simplicity, good yields, as well as widespread applications, leading to a facile and straightforward admittance to structurally diverse 2-substituted aminobenzimidazole analogues with potential bioactivities.     

Intermolecular alkyl/aryl exchange of 2-iminothiazoles with isothiocyanates and isocyanates: scopes and limitations

2-Iminothiazole, an isoform of 2-aminothiazole, is a scaffold of synthetic and medicinal significance. We have reported an efficient method by which alkyl group of 2-alkyliminothiazoles is changed into other alkyl groups by isothiocyanates. In this article, a detailed mechanistic aspect, and the scopes and limitations were disclosed. All the reactions were carried out in toluene at 105 °C without any additive. The reaction is a reversible process and the equilibrium is determined by the reactivity of both reactants, in which the more electron-withdrawing alkyl or aryl groups at the 2-imino group or isothiocyanate showed higher reactivities. With this simple method, we effectively altered the alkyl group attached on the imine nitrogen. A synthetic problem in 2-iminothiazole chemistry, synthesis of amino acid-derived 2-iminothiazole was solved in a very simple manner. Using suitably designed 2-iminothiazole substrate, the electrophilic reactivity of various isothiocyanates could be empirically compared by this exchange reaction. Moreover, successful exchange reaction using isocyanates instead of isothiocyanates broadened the utility of this reaction.     

Tandem addition–cyclization of o-ethynylphenyl isothiocyanates with N nucleophiles; difference of cyclization mode between primary and secondary amines

Silver triflate promotes the 6-exo-dig mode cyclization of the N-(2-ethynylphenyl)thioureas, which were easily obtained from the o-ethynylphenyl isothiocyanates and the primary amines, to provide the 2-imino-4-methylidene-1H-benzo[d][1,3]thiazines as the sole product in excellent yields. The secondary amines reacted with the o-ethynylphenyl isothiocyanates to give both the 6-exo and 5-endo-dig mode cyclization products under the same conditions.     

Synthesis of substituted thiazolo[4,5-b]pyridines and other annulated heterocycles via SN2→Thorpe-Ziegler→Thorpe-Guareschi domino reactions

A new combinatorial method for the preparation of substituted thiazolo[4,5-b]pyridines, which utilizes cyanoacetamide, heterocumulenes (isothiocyanates, carbon bisulfide), and ethyl-4-chloroacetoacetate in a new S_N2→Thorpe-Ziegler→Thorpe-Guareschi domino reactions has been developed. The obtained thiazolo[4,5-b]pyridines were then used together with aldehydes and malononitrile in another Knoevenagel reaction→Michael reaction→hetero-Thorpe-Ziegler domino reaction for the synthesis of substituted 4,6-dihydro-5H-pyrano[2,3-d]thiazolo[4,5-b]pyridines.     

NHC-catalyzed enantioselective [2 + 2] and [2 + 2 + 2] cycloadditions of ketenes with isothiocyanates

The enantioselective N-heterocyclic carbene-catalyzed formal [2 + 2] and [2 + 2 + 2] cycloaddition of ketenes and isothiocyanates were developed. Reaction with N-aryl isothiocyanates at room temperature favors the [2 + 2] cycloaddition, while reaction with N-benzoyl isothiocyanates at -40 °C favors the [2 + 2 + 2] cycloaddition.     

Merrifield resin supported phenanthroline-Cu(I): a highly efficient and recyclable catalyst for the synthesis of 2-aminobenzothiazoles via the reaction of 2-haloanilines with isothiocyanates

A novel Merrifield resin supported phenanthroline-Cu(I) complex has been developed and used as a highly efficient and recyclable catalyst in the reaction of 2-halobenzenamines with isothiocyanates for the synthesis of 2-aminobenzothiazoles. The reactions were applicable to a variety of 2-halobenzenamines and isothiocyanates, and generated the corresponding 2-aminobenzothiazoles in good yields under mild reaction conditions. Moreover, the catalyst was quantitatively recovered from the reaction mixture by a simple filtration and reused for ten cycles with almost consistent activity.     

Highly site, regio-, and stereoselective multicomponent reaction of benzimidazole carbenes, isothiocyanates, and allenoates

The novel three-component reaction of benzimidazole carbenes with isothiocyanates and allenoates proceeded efficiently in a highly site, regio-, and stereoselective manner to produce predominantly spiro[benzimidazoline-2,3′-tetrahydrothiophene] derivatives. The reaction was proposed to occur via a tandem nucleophilic addition of carbenes to isothiocyanates followed by an unusual [3+2] cycloaddition to the less activated carbon-carbon double bond of allenoates.