Rapid, microwave-assisted synthesis of N1-substituted 3-amino-1,2,4-triazoles

A robust, regioselective synthesis of 3-amino-1,2,4-triazoles is described. This reaction employs a key intermediate 2, which is coupled to carboxylic acids in good yields to afford intermediates 3a-d. These entities, in turn, react with a variety of hydrazines or hydrazine hydrochlorides to provide proposed intermediates 4a-j, which under microwave conditions cyclize to the desired 3-amino-1,2,4-triazoles (compounds 5a-j). This approach permits the rapid synthesis of regioselective N1-substituted 3-amino-1,2,4-triazoles, and is shown to afford a variety of such compounds in 34-70% isolated yields.     

Multicomponent synthesis of dihydropyrimidines and thiazines

A broad range of differently substituted dihydropyrimidines and thiazines can be efficiently prepared by using a four-component reaction between phosphonates, nitriles, aldehydes, and iso(thio)cyanates. The scope and limitations of this multicomponent reaction are fully described. Variation of all four components has been investigated. The nitrile and aldehyde inputs can be varied extensively, but variation of the phosphonate input remains limited. An interesting rearrangement leading to phosphoramidates has been observed. Furthermore, the multicomponent reaction seems to be restricted to the use of isocyanates with strongly electron-withdrawing substituents, but an interesting additional exchange reaction under microwave conditions leads to dihydropyrimidines with less electron-withdrawing substituents at N3. In addition, a diastereoselective formation of dihydropyrimidines has been observed when using a chiral aldehyde as the input. Finally, by changing the isocyanate component to an isothiocyanate, thiazines are efficiently formed instead of the corresponding thio-dihydropyrimidines.     

The synthesis and properties of 2-substituted dihydropyrimidines

Various 2-substituted 1,4-dihydro-4,4,6-trimethyl-1-phenylpyrimidines and 1,6-dihydro-4,6,6-trimethylpyrimidines were synthesized independently. For these dihydropyrimidines, the physical data such as the uv, ir, and nmr spectra and the oxidation potential were compared. 2-Dimethylamino substituted dihydropyrimidine showed the lowest oxidation potential, which expected the similar reducing ability as dihydropyridines.     

Application of DMF-methyl sulfate adduct in the regioselective synthesis of 3-acylated indolizines

A number of 3-acylated indolizines were synthesized in good to excellent yields by a newly established reaction between picolinium salts and the methylsulfate salt of A (R = Me), the adduct formed from DMF-Me₂SO₄ as the key reagent. The low cost, short reaction time, mild reaction condition, and easy purification of the products make this an attractive new method for the synthesis of indolizine compounds. A variety of functional groups (nitro, cyano, ester, methoxy, and halogens) were well tolerated under the reaction conditions.     

One-pot synthesis of dihydropyrimidines via eco-friendly phosphorus derivatives catalysis

A straightforward, cost effective and eco-friendly protocol for the Biginelli reaction relying on the use of readily available hypophosphorous acid is presented. The methodology developed displays improvements compared to existing methods, is high-yielding, robust and was applied to a panel of dihydropyrimidines and thio-derivatives with various substituents. Related urea derivatives such as guanidines, benzimidazoles and benzothiazoles also reacted efficiently to afford more complex scaffolds. Thus, this rapid and convenient catalysis allows access to a wide diversity of structures including original biologically relevant heterocycles.     

A one-pot two-step microwave-assisted synthesis of N1-substituted 5,6-ring-fused 2-pyridones

A fast, versatile and practical one-pot, two-step microwave-assisted protocol for the direct synthesis of N1-substituted 5,6-ring-fused 2-pyridones has been developed. The present method proved to be effective on a series of commercially available aldehydes, ketones and amines and could be profitably exploited in drug-discovery settings for the rapid identification of biologically relevant hit compounds.     

High-throughput microwave-assisted organic synthesis: moving from automated sequential to parallel library-generation formats in silicon carbide microtiter plates

A 48 deep-well microtiter plate system for sealed vessel parallel microwave synthesis is described. The plate consists of a standard 6 x 8 matrix of 48 wells with a maximum working volume of 300 microL and is made out of strongly microwave-absorbing sintered silicon carbide. In combination with an alumina sealing plate equipped with adequate conical bore holes for sample withdrawal, the setup can be used for microwave processing at temperatures up to approximately 200 degrees C and 20 bar of pressure. The microtiter plate setup displays excellent temperature and reaction homogeneity and was used for the generation of a 30-member library of 2-aminopyrimidines.     

A novel four-component reaction for the synthesis of functionalised dihydropyrimidines

In a multi-component reaction (MCR) of a phosphonate, nitriles, aldehydes and isocyanates, N3-functionalised dihydropyrimidines can be synthesised efficiently via a Horner-Emmons/aza Diels-Alder pathway.     

Efficient microwave-assisted synthesis of 3-benzothiazolo and 3-benzothiazolino coumarin derivatives catalyzed by heteropoly acids

Heteropoly acids are reported as efficient catalysts for the microwave-assisted synthesis of 3-benzothiazolo and 3-benzothiazolino coumarin from o-aminothiophenol derivatives with 3-acetly and 3-cyanochromen-2-one in good to excellent isolated yields (73?C95%). This study suggests new techniques for the synthesis of chromene derivatives using an inexpensive and easily available catalyst, a simple procedure, short reaction time, and good to excellent yields of the products.     

5-aroyl-3,4-dihydropyrimidin-2-one library generation via automated sequential and parallel microwave-assisted synthesis techniques

An efficient two-step synthetic pathway toward the preparation of diversely substituted 5-aroyl-3,4-dihydropyrimidin-2-ones is realized. The protocol involves an initial trimethylsilyl chloride-mediated Biginelli multicomponent reaction involving S-ethyl acetothioacetate, aromatic aldehydes, and ureas as building blocks to generate a set of 3,4-dihydropyrimidine-5-carboxylic acid thiol esters. These thiol esters serve as starting materials for a subsequent Pd-catalyzed Cu-mediated Liebeskind-Srogl cross-coupling reaction with boronic acids to provide the desired 5-aroyl-3,4-dihydropyrimidin-2-one derivatives. Both steps were performed using microwave heating in sealed vessels, either in an automated sequential or parallel format using dedicated microwave reactor instrumentation. A diverse library of 30 5-aroyl-3,4-dihydropyrimidin-2-ones was prepared with commercially available aldehyde, urea, and boronic acid building blocks as starting materials.     

High-throughput synthesis and analysis of acylated cyanohydrins

The yields and optical purities of products obtained from chiral Lewis acid/Lewis base-catalysed additions of alpha-ketonitriles to prochiral aldehydes could be accurately determined by an enzymatic method. The amount of remaining aldehyde was determined after its reduction to an alcohol, whilst the two product enantiomers were analysed after subsequent hydrolysis first by the (S)-selective Candida antarctica lipase B and then by the unselective pig liver esterase. The method could be used for analysis of products obtained from a number of aromatic aldehydes and aliphatic ketonitriles. Microreactor technology was successfully combined with high-throughput analysis for efficient catalyst optimization.     

High-throughput synthesis and screening of hydrogen-storage alloys

Libraries of mixed-metal hydride materials are synthesized on a silicon microfabricated array of "hot-plate" MEMS devices, which allow high-throughput screening using temperature programmed desorption and infrared thermography. The heating plate of the MEMS device is a membrane with low heat capacity, allowing fast and localized temperature control and the extraction of calorimetric data from thermography. The combination of the synthetic method and screening chip allows a fast determination of the desorption temperature and hydrogen content of the materials. Mixed metal hydrides are synthesized directly. The potential of the method is exemplified by presenting results for the sorption properties of Mg xNi 1- x hydride thin-film materials. The results are consistent with the literature, showing the highest hydrogen capacity and desorption temperature for the MgH 2 phase in Mg-rich compositions and the promotion of a lower temperature desorption from the Mg 2NiH 4 phase, with a concomitant reduction in hydrogen capacity.     

Efficient ytterbium triflate catalyzed microwave-assisted synthesis of 3-acylacrylic acid building blocks

The derivatives of 4-(hetero)aryl-4-oxobut-2-enoic acid are useful as building blocks in the synthesis of biologically active compounds. An efficient general protocol for the synthesis of these building blocks was developed. This method combines microwave assistance and ytterbium triflate catalyst and allows the fast preparation of the target acids starting from different (hetero)aromatic ketones and glyoxylic acid monohydrate giving pure products in 52-75% isolated yields.     

Highly fluorescent Ag nanoclusters: microwave-assisted green synthesis and Cr3+ sensing

Highly fluorescent Ag nanoclusters were prepared in aqueous solution via a rapid microwave-assisted green approach and used as a novel fluorescence probe for the determination of Cr(3+) ions with high sensitivity and excellent selectivity.     

Coupling sol-gel synthesis and microwave-assisted techniques: a new route from amorphous to crystalline high-surface-area aluminium fluoride

A non-aqueous sol-gel Al-based fluoride has been subjected to the microwave solvothermal process. The final material depends on the temperature heat treatment used. Three types of material have been prepared: 1) for low temperature heat treatment (90 degrees C) X-ray amorphous alkoxy fluoride was obtained; 2) for the highest temperature used (200 degrees C) the metastable form beta-AlF3 was obtained with a very large surface area of 125 m2 g(-1). The mechanism of the amorphous=crystalline transformation has been rationalised by the occurrence of a decomposition reaction of the gel fluoride induced by the microwave irradiation. 3) Finally, at intermediate temperature (180 degrees C) a multi-component material mixture exhibiting a huge surface area of 525 m2 g(-1) has been obtained and further investigated after mild post-treatment fluorination using F2 gas. The resulting aluminium-based fluoride still possesses a high-surface-area of 330 m2 g(-1). HRTEM revealed that the solid is built from large particles (50 nm) identified as alpha-AlF3, and small ones (10 nm), relative to an unidentified phase. This new high-surface-area material exhibits strong Lewis acidity as revealed by pyridine adsorption and catalytic tests. By comparison with other materials, it has been shown that whatever the composition/structure of the Al-based fluoride materials, the number of strong Lewis acid sites is related to the surface area, highlighting the role of surface reconstruction occurring on a nanoscopic scale on the formation of the strongest Lewis acid sites.     

Oxidative dehydrogenation of dihydropyrimidinones and dihydropyrimidines

[reaction: see text] A mild, practical procedure for oxidative dehydrogenation with catalytic amounts of a Cu salt, K2CO3, and tert-butylhydroperoxide (TBHP) as a terminal oxidant has been developed. This oxidation procedure is generally applicable to dihydropyrimidinones and most dihydropyrimidines.     

One-pot and microwave-assisted synthesis of N-sulfonylaziridines

A novel and efficient microwave-assisted one-step reaction was developed to synthesize chiral N-sulfonylaziridines by the reaction of different chiral amino alcohols and sulfonic chlorides. The newly developed microwave synthetic method has the advantage of reducing the reaction time from 24 to 0.5 h with improved yields (84-93%) and minimizing by-products.     

Ferrocenecarboxylic acid and microwave-assisted synthesis of ferrocenoyl hydrazones

Russian Chemical Bulletin - A protocol to access ferrocenecarboxylic acid via carboxylation of ferrocene with carbon dioxide in the presence of aluminum chloride was elaborated. An efficient...     

Selective synthesis of poly-substituted fluorine-containing pyridines and dihydropyrimidines via cascade C-F bond cleavage protocol

Fluorinated azaheterocycles are frequently found in pharmaceuticals, drug candidates, ligands for transition metal catalysts, and other molecular functional materials, so efficient methods for the synthesis of these compounds are of significant value. We herein describe a selective strategy for the synthesis of poly-substituted pyridines and fluoroalkyl dihydropyrimidines based on C-F bond breaking of the anionically activated fluoroalkyl group. An array of pyridines and dihydropyrimidines were prepared through this domino process in high yields under noble metal catalyst-free conditions, making this method a valuable supplement to azaheterocycle synthesis.