Efficient and rapid synthesis of 1-substituted-1H-1,2,3,4-tetrazoles in the acidic ionic liquid 1-n-butylimidazolium tetrafluoroborate

An efficient synthesis leading directly to 1-substituted-1H-1,2,3,4-tetrazoles from easily available amines and sodium azide in stoichiometric proportions using a room-temperature ionic liquid, namely, 1-n-butylimidazolium tetrafluoroborate in excellent yields is described. The inherent Brønsted acidity and high polarity of the IL results in a significant enhancement in the reaction rate.     

5-Benzyl-1H-tetrazols from the reaction of 1-aryl-5-methyl-1H-tetrazoles with 1,2-dehydrobenzene

A series of 1-aryl-5-benzyl-1H-tetrazoles has been obtained during the reaction of 1-aryl-5-methyl-1H-tetrazoles with 1,2-dehydrobenzene. The mechanism of product formation was investigated.     

Gallium(III) triflate-catalyzed one-pot selective synthesis of 2,3-dihydroquinazolin-4(1H)-ones and quinazolin-4(3H)-ones

A series of 2,3-dihydroquinazolin-4(1H)-ones and quinazolin-4(3H)-ones have been synthesized in good to excellent yields and high selectivity by one-pot reaction using isatoic anhydride, ammonium acetate (or amines), and aldehydes in ethanol or in DMSO under mild conditions, respectively. The reaction was efficiently promoted by 1 mol % Ga(OTf)₃ and the catalyst could be recovered easily after the reactions and reused without evident loss of reactivity.     

Versatile synthesis of chiral 2-substituted-5-oxo-1,2,3,4-tetrahydro-5H-1,4-benzodiazepines as novel scaffolds for peptidomimetic building

The stereocontrolled synthesis of phenylalanine and tryptophan derived 5-oxo-1,2,3,4-tetrahydro-5H-1,4-benzodiazepine derivatives is described. This new methodology involves a modified Strecker reaction of N-Boc protected amino aldehydes and methyl anthranilate, reduction of the resulting α-amino nitriles, and lactamization. The resulting 2-substituted-5-oxo-1,2,3,4-tetrahydro-5H-1,4-benzodiazepines were further functionalized at position 4 by alkylation or acylation reactions. One of these new tryptophan-derived 1,4-benzodiazepines showed significant selective binding affinity at cholecystokinin CCK₁ receptors (IC₅₀=156.5±33.2 nM).     

On the explosive properties of 1H-benzotriazole and 1H-1,2,3-triazole

For 1H-benzotriazole, no explosive properties are observable, but the relative high exothermic decomposition energy of 1590 J/g should be kept in mind. Nevertheless, an endothermic melting barrier at 100 °C ensures safe handling at lower temperatures. For 1H-1,2,3-triazole, the exothermic decomposition energy is as high as 2600 J/g, but explosive properties are also not detectable. Therefore, both reagents are hazardous with regard to the exothermic decomposition potential and can be handled safely with precautions.     

Facile, diversity-orientated one-pot synthesis of ethyl 1,5-disubstituted-1H-1,2,4-triazole-3-carboxylates

Access to the 1,5-disubstituted-1H-1,2,4-triazole-3-carboxamide motif is quite laborious and requires forcing conditions to effect the cyclocondensation step. Herein, we report an efficient and mild one-pot protocol to access this substructure in good chemical yields with high regiocontrol.     

Synthesis of 1,2,3,4-tetrahydroisoquinolines and 2,3,4,5-tetrahydro-1H-2-benzazepines combining sequential palladium-catalysed ortho alkylation/vinylation with aza-Michael addition reactions

1-Substituted 1,2,3,4-tetrahydroisoquinolines and 2,3,4,5-tetrahydro-1H-2-benzazepines were synthesised from o-iodoalkylbenzene, N-Cbz-bromoalkylamine and an electron-poor olefin through a one-pot palladium-catalysed sequence involving ortho alkylation, alkenylation and intramolecular aza-Michael reaction.     

TaBr5-catalyzed Biginelli reaction: one-pot synthesis of 3,4-dihydropyrimidin-2-(1H)-ones/thiones under solvent-free conditions

An efficient TaBr₅ (5-10 mol %)-catalyzed Biginelli reaction under solvent-free conditions for one-pot syntheses of 3,4-dihydropyrimidin-2-(1H)-ones (DHPMs) and their thione analogs is reported. The catalyst is stable at room temperature and employed under mild and environmentally friendly conditions.     

A new enlargement methodology for the preparation of 2H-1- and 2H-3-benzazepin-2-one derivatives

An investigation of the one-carbon homologation of some 1-tribromomethyl-isoquinoline and 2-tribromomethyl-quinoline derivatives was conducted. Under the influence of an aqueous solution of silver nitrate in the presence of a nucleophilic species (MeOH, H₂O, EtNH₂), these derivatives led to the respective expanded heterocycles, 2H-1- and 2H-3-benzazepin-2-one derivatives. A mechanism for this novel ring enlargement involving initial formation of an aziridinium, and its subsequent opening to form a stabilized benzylic carbocation, is proposed to explain the results.     

Microwave-assisted synthesis of 1-aryl-1H-indazoles via one-pot two-step Cu-catalyzed intramolecular N-arylation of arylhydrazones

A highly efficient one-pot two-step microwave procedure was developed for the synthesis of 1-aryl-1H-indazoles. Microwave heating of 2-halobenzaldehydes or 2-haloacetophenones with phenylhydrazines at 160 °C for 10 min quantitatively yielded the arylhydrazones, which were further cyclized to give 1-aryl-1H-indazoles via CuI/diamine-catalyzed N-arylation under microwave heating (160 °C, 10 min). Good to excellent yields were observed for 2-iodo, 2-bromo, and 2-chloro benzaldehydes or acetophenones.     

The one-pot synthesis of 4-aryl-1H-1,2,3-triazoles without azides and metal catalization

In this study, a new methodology for the one-pot synthesis of 4-aryl-1H-1,2,3-triazoles from arylglyoxaldoxime semicarbazone is presented. 4-Aryl-1,2,3-triazoles were obtained in moderate to good yields via sodium dithionite and O₂, which are all efficient, safe and inexpensive reagents. This reaction is more suitable for large-scale syntheses than those using hydrazoic acid, sodium azide, or organic azides.     

A hetero-Diels-Alder approach to functionalized 1H-tetrazoles: synthesis of tetrazolyl-1,2-oxazines, -oximes and 5-(1-aminoalkyl)-1H-tetrazoles

This work describes the first and unprecedented examples of inverse electron demand Diels-Alder reactions of 5-(1-nitrosovinyl)-1-phenyl-1H-tetrazole, generated in situ from the corresponding bromooxime, with electron rich alkenes and heterocycles, providing in good overall yields tetrazolyl-1,2-oxazines and -oximes. Upon subsequent reduction these allowed the access to 5-(1-aminoalkyl)-1H-tetrazoles, paving the way for a new entry into this important class of compounds, bioisosteres of α-amino acids.     

Preyssler catalyst-promoted rapid,clean, and efficient condensation reactions for 3H-1,5-benzodiazepine synthesis in solvent-free conditions

A simple, convenient, and environmentally benign synthesis of 1,5-benzodiazepines is developed by condensing different o-phenylenediamines and 1,3-aryl-1,3-propanodiones. The reaction is catalyzed by a Preyssler (NaH₁₄P₅W₃₀O₁₁₀, HPA) heteropolyacid as a safe, clean, and recyclable catalyst. The method is operationally simple and provides access to a variety of 1,5-benzodiazepines in good to excellent yields.     

A novel and convenient route for the construction of 5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indoles and its application in the synthesis of Rizatriptan

In this study, a novel and convenient route for the construction of 5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indoles (8) is presented starting from (1H-1,2,4-triazol-1-yl)methanol (5) and indolines (6) under 98% H₂SO₄ at room temperature for 4–24 h, followed by deacetylation and dehydrogenation. Based on this finding, a novel route to synthesize Rizatriptan starting from tryptamine was designed and accomplished with 48.5% overall yield in 6 steps. Compared with operational art, the new route afforded higher yield and more pure products requiring no chromatographic purification, which may further be applied in industrialization.     

New three-component cyclocondensation reaction: microwave-assisted one-pot synthesis of 5-unsubstituted-3,4-dihydropyrimidin-2(1H)-ones under solvent-free conditions

Sixteen 5-unsubstituted-3,4-dihydropyrimidin-2(1H)-ones have been synthesized by microwave-assisted Biginelli reactions in a short and concise manner employing ZnI₂ as a catalyst under solvent-free conditions. All products were identified by IR, NMR, elemental analysis and HRMS. The advantages of this novel protocol include the excellent yield, operational simplicity, short time and the avoidance of the use of organic solvents and expensive catalysts.     

Eco-friendly synthesis of guanidinyltetrazole compounds and 5-substituted 1H-tetrazoles in water under microwave irradiation

We have developed simple, short time, cost effective, purification of products by non-chromatographic methods and environmentally benign protocol for the synthesis of guanidinyltetrazoles and 5-substituted 1H-tetrazoles derivatives via [2,3]cyclo-addition reaction of nitriles and azide derivatives in water under microwave irradiation. All the synthesized products are screened for their in vitro antimicrobial activity. The synthesized compounds were obtained in excellent yield (85–98%).     

Synthesis of 5-substituted 1H-tetrazoles catalyzed by ytterbium triflate hydrate

Various 5-substituted 1H-tetrazoles were synthesized from aryl nitriles, alkyl nitriles, and vinyl nitriles reacting with sodium azide. The tetrazoles were recovered in high yield under mild conditions when the reaction was catalyzed by ytterbium triflate hydrate in dimethylformamide. Other rare-earth and post-transition metal catalysts were also investigated.     

A new efficient method for the synthesis of 3,4-dihydro-2H-1,4-benzoxazines via iodocyclization

An efficient approach for the synthesis of 3,4-dihydro-2H-1,4-benzoxazine derivatives is described by molecular iodine- mediated cyclization. The reaction condition is very simple, offers easy isolation, and affords good to excellent yields of the products.     

Ring-closing metathesis for the synthesis of 2H- and 4H-chromenes

Six 4H-chromenes were synthesized from substituted phenols using vinylstannylation and ring-closing metathesis (RCM) as key steps. In addition, a different approach involving amongst other steps, an aryl allyl isomerization and RCM afforded a set of seven 2H-chromenes from phenolic precursors.