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.     

A convenient and efficient method for the synthesis of mono- and N,N-disubstituted thioureas

A convenient method for the synthesis of mono- and N,N-disubstituted thioureas by the debenzoylation of N-substituted- and N,N-disubstituted-N′-benzoylthioureas with hydrazine hydrate under solvent-free conditions has been developed. N-Substituted-N′-benzoylthioureas and hydrazine hydrate were mixed, and stirred at room temperature without a solvent to give the corresponding N-substituted thioureas in high yields.     

Regio-controlled synthesis of N-substituted imidazoles

A regio-specific synthesis of N-substituted imidazoles is described. Readily available α-amino acids are converted to α-aminocarbonyl derivatives and reacted with various isothiocyanates to give N-substituted cyclic thioureas. Oxidative or reductive desulfurization of the cyclic thioureas affords structurally diversified imidazoles in good to excellent yields.     

Efficient synthesis of N,N′-dialkyl-N″-dialkylaminocarbothioyl thioureas from cyclic secondary amines, CS2, and N,N′-dialkyl carbodiimides in water

A mild, convenient, and practical one-pot procedure for direct synthesis of N,N′-dialkyl-N″-dialkylaminocarbothioyl thioureas is described via three-component reaction of cyclic secondary amines, CS₂, and N,N′-dialkyl carbodiimides in water at room temperature.     

A practical synthesis of 2-(N-substituted)-aminobenzimidazoles utilizing CuCl-promoted intramolecular cyclization of N-(2-aminoaryl)thioureas

A practical protocol for synthesis of 2-(N-substituted)-aminobenzimidazoles was developed. N-(2-Aminoaryl)thioureas undergo a CuCl-promoted intramolecular cyclization to give the corresponding 2-(N-substituted amino)benzimidazoles in good to excellent isolated yields.     

Regioselective synthesis of N-acetylureas by manganese(III) acetate reaction of 1,3-disubstituted thioureas

Reactions of asymmetrical 1,3-disubstituted thioureas with manganese(III) acetate produce regioselective N-acetylureas. A mechanism for this novel transformation is proposed.     

An efficient method for the synthesis of disubstituted thioureas via the reaction of N,N′-di-Boc-substituted thiourea with alkyl and aryl amines under mild conditions

An efficient method for the synthesis of disubstituted thioureas via the reaction of N,N′-di-Boc-substituted thiourea 5 with alkyl and aryl amines under mild conditions has been developed. In the presence of NaH as a base, trifluoroacetic anhydride (TFAA) reacted with 5 providing intermediate 6, which then reacted with amines giving thioureas 7 in excellent yields. This reaction conditions tolerated other functional groups such as amide, ester, enol ether and hydroxyl groups.     

Selective functionalization at the small rim of calix[6]arene. Synthesis of novel non-symmetrical N3, N4 and N3ArO biomimetic ligands

Eight novel calix[6]arene-based biomimetic ligands for transition metal ions have been synthesized. They display a non-symmetrical N₃, N₄ or N₃ArO binding core that mimics enzyme active sites presenting histidine and tyrosine residues. The key step for their synthesis is the mono-alkylation at the small rim of the C_3v symmetrical trimethyl ether derivative of tBu-calix[6]arene with N-Boc-2-chloroethylamine to yield a novel calix[6]arene synthon. Its combined O-alkylation with a chloromethyl aromatic amine and N-deprotection or alkylation or reductive alkylation with a salicylaldehyde derivative yielded the calix[6]arene-based ligands with mixed N/O donors.     

A concise synthesis of asymmetrical N,N′-disubstituted guanidines

We present a new and concise method for the preparation of asymmetrical N,N′-disubstituted guanidines starting from thiourea via the reaction of N-Boc-protected N′-alkyl/aryl substituted thioureas with an amine in the presence of mercury(II) chloride and triethylamine.     

Diversity-oriented synthesis of N-aryl-N-thiazolyl compounds

An efficient approach toward the parallel solid-phase synthesis of highly diversified N-aryl-N-thiazolyl compounds is presented. The treatment of resin-bound aniline derivatives with Fmoc-isothiocyanate generated aryl thioureas which, following Hantzsch’s reaction with a variety of α-haloketones and cleavage of the solid support, led to the desired N-aryl-N-thiazolyl compounds in good yield and high purity.     

Two-pot synthesis of N,N-disubstituted 4H-3,1-benzothiazin-2-amines from aryl(2-isothiocyanatophenyl)methanones and secondary amines

A convenient synthesis of N,N-disubstituted 4H-3,1-benzothiazin-2-amines from aryl(2-isothiocyanatophenyl)methanones using a two-pot procedure has been developed. Thus, treatment of these isothiocyanato ketones with secondary amines gave the corresponding keto thioureas, which were allowed to react with sodium borohydride or methylmagnesium bromide to afford 1,1-dialkyl-3-{2-[aryl(hydroxy)methyl]phenyl}thioureas or 1,1-dialkyl-3-[2-(1-aryl-1-hydroxyethyl)phenyl]thioureas, respectively, in one pot. Hydrobromic acid-mediated cyclization of these hydroxy thiourea precursors provided the desired 4H-3,1-benzothiazin-2-amines.     

Phosphonium-mediated cyclization of N-(2-aminophenyl)thioureas: efficient synthesis of 2-aminobenzimidazoles

BOP efficiently promoted the phosphonium-mediated cyclization of thioureas, leading to a convenient synthesis of 2-aminobenzimidazoles. Compared to conventional methods, the reactions were complete at room temperature with times ranging from a few minutes to 1 h in near quantitative yields. This method is also applicable to the synthesis of more challenging structures such as 2-akylaminobenzimidazoles and 2-(N-acyl)-aminobenzimidazoles. The methodology described herein represents a mild and efficient route to a variety of 2-aminobenzimidazoles.     

New tetrasubstituted thioureas containing the 1-iminoethyl moiety

The reactions of 1,1,3-trisubstituted thioureas with acetonitrile afforded the corresponding tetrasubstituted thioureas containing the N-(1-iminoethyl) moiety.     

Pyridinium N-heteroarylaminides: synthesis of N-heteroarylpolyamines

The synthesis of a set of new N-heteroarylpolyamines is reported. A multiple and regioselective alkylation on the exo nitrogen of pyridinium N-(heteroaryl)aminides with several polybromo compounds, followed by a clean N-N bond reduction of the corresponding pyridinium salts, provides an easy and general method to obtain the title compounds.     

Reductive coupling of aromatic N,N-acetals using zinc and chlorotrimethylsilane

The reductive coupling of aromatic N,N-acetals and N,O-acetal activated by chlorotrimethylsilane proceeded smoothly in the presence of zinc to give the corresponding diamines in good yields.     

Single-step conversion of N-benzyl, N-trityl and N-diphenylmethyl amines to t-butyl carbamates using polymethylhydrosiloxane

t-Butyl carbamates were obtained efficiently in high yields from the corresponding N-benzyl, N-trityl and N-diphenylmethyl precursors in a single-step reductive transformation employing polymethylhydrosiloxane and di-t-butyl dicarbonate under Pd(OH)₂/C catalysis.     

A new efficient synthetic strategy for N-(dialkylamino)azacycle as a tetrasubstituted hydrazine derivative using sodium triacyloxyborohydride

A new efficient and convergent method has been developed to construct a N-(dialkylamino)azacyclic system as a tetrasubstituted hydrazine via reductive alkylation of the corresponding hydrazone using sodium triacyloxyborohydride [NaBH(OCOR)₃], which is tolerant of various substituents (e.g., phenol, conjugated olefin, amide, and thioamide) on the substrate and useful for organization of the N-aminoazacycle array.     

Polymer-supported N-benzyl- and N-benzhydryl-2-nitrobenzenesulfonamides as alternative to aldehyde linkers

Polymer-supported N-benzyl- and N-benzhydryl-2-nitrobenzenesulfonamides 1 were N-alkylated using three different routes: via Fukuyama reaction with alcohols, by N-alkylation with electrophiles, and by Michael addition reaction with α,β-unsaturated carbonyl compounds. The N-alkylated products were obtained in excellent purity and high yield. The 2-nitrobenzenesulfonyl (Nos) group was then cleaved to yield polymer-supported N-alkylated benzylamines and benzhydrylamines. N-alkylation of polymer-supported 2-nitrobenzenesulfonamide linkers 1 described herein represents an alternative route to reductive amination of aldehyde linkers.     

Palladium-catalyzed N-heteroannulation of N-allyl- or N-benzyl-2-nitrobenzenamines: synthesis of 2-substituted benzimidazoles

A palladium-catalyzed reductive N-heteroannulation of N-allyl- or N-benzyl-2-nitrobenzenamines, using carbon monoxide as the ultimate reducing agent, affording 2-substituted benzimidazoles has been developed.     

Two-step N-acylindazole to N-alkylindazole reduction. Further synthetic studies on the serotonergic agonist AL-34662

A synthesis of the title compound, operable on kilogram scale, employs reductive acetylation of an N-acylindazole to give a hemiaminal acetate followed by deacetoxylation to the corresponding N-alkylindazole.