A new three-carbon synthon for efficient synthesis of benzannelated and 1-(2-arylethenyl) heterocycles

The novel three-carbon synthon 1-(1H-1,2, 3-benzotriazol-1-yl)-3-chloroacetone for the synthesis of benzothiazoles, pyrido[1,2-a]indoles, and styryl-substituted indolizines and imidazo[1,2-a]pyridines is reported. The proposed routes are a general and efficient approach for heterocyclizations followed by benzannelations or attachment of arylethenyl pharmacophores.     

Rapid Ti(Oi-Pr)4 facilitated synthesis of α,α,α-trisubstituted primary amines by the addition of Grignard reagents to nitriles under microwave heating conditions

A series of carbinamines (α,α,α-trisubstituted amines) have been prepared in a simple and efficient one-pot procedure by the addition of Grignard reagents to a series of aliphatic, aromatic and heteroaromatic nitriles. The resulting magnesium imines are subsequently converted to the desired amine after treatment with Ti(Oi-Pr)₄ and additional microwave heating. Key to this procedure is the use of microwave heating for both steps of the reaction protocol, which significantly improves both reaction yields and reduces reaction times. In general, the Grignard addition reaction is complete within 5-10 min at 100 °C followed by conversion with Ti(Oi-Pr)₄ and additional microwave heating to give the target amines in good yields.     

Synthesis of pyrido[4,3,2-de]quinazolines via nitro-substituted tetrahydroquinolines

The simple and efficient synthesis of novel dihydropyrido[4,3,2-de]quinazolines in four steps from m-nitroaniline is described.     

Expedient Lewis acid catalyzed synthesis of a 3-substituted 5-arylidene-1-methyl-2-thiohydantoin Library

An efficient and rapid solution phase combinatorial synthesis of a 3-substituted 5-arylidene-1-methyl-2-thiohydantoin library was developed. The salient feature for this library production procedure is the addition of the Lewis acid catalyst, indium(III) trifluoromethanesulfonate, which serves to facilitate the direct condensation of aldehydes with 3-substituted 1-methyl-2-thiohydantoins. Use of this Lewis acid catalyst has resulted in faster reaction times, higher conversions and better purity profiles for these condensation reactions as compared to traditional uncatalyzed reactions. The resulting 315 member library of 3-substituted 5-arylidene-1-methyl-2-thiohydantoin is described.     

Rapid, one-pot synthesis of α,α-disubstituted primary amines by the addition of Grignard reagents to nitriles under microwave heating conditions

A series of α,α-disubstituted amines have been prepared in a simple and efficient one-pot procedure by the addition of Grignard reagents to a series of aliphatic, aromatic, and heteroaromatic nitriles. Key to this reported procedure is the unprecedented addition of the Grignard reagent to the nitrile under heating by microwave irradiation which both significantly improves reaction yields and reduces reaction times. In general, the Grignard addition reaction is complete within 5-10 min at 100 °C followed by rapid reduction with sodium borohydride to give the target amines.     

Parallel esterification of bio-based dicarboxylic acids in small scale film reactors: A high-throughput study

The applicability of polyesters across a wide range of fields creates a demand for novel polyester structures that can offer advanced product performance. Two critical factors to the development of unique polymer architectures are the speed at which new polymeric systems can be synthesized and the available selection of monomers from which polymers are designed. Herein, we successfully demonstrate the applicability of a high-throughput (HT) approach to polyesterification reaction between dicarboxylic acids and diols in reaction conditions similar to those used in industry. Furthermore, we apply our HT design to a series of bio-based monomers whose unique structures offer potential for enhanced properties in polyester-based systems. Using a custom-built array of small-scale film reactors, we conducted a parallel screening of 13 bio-based dicarboxylic acids as potential monomers in the synthesis of polyester polyols through copolymerization with 1,6-hexanediol. The polyester polyols were characterized for their molecular weight and thermal properties. Carrying out polyesterification reactions in small-scale film reactors is seen as a quick and powerful tool for screening the effectiveness of a series of potential monomers, as this method offers highly controllable and reproducible reaction conditions in every reactor coupled with the ability to use a minimum amount of reagents.     

Polymer-supported triazole and benzotriazole leaving groups. Three new examples and a comparison of their efficiency

Three polymer-supported heterocyclic (triazole 4 and benzotriazoles 2, 8) leaving groups are described. The loading of 8 was clearly superior to those of 2 and 4. The efficiency of 8 was higher than those of previously reported benzotriazole resins 9a,b in the C-acylation of ketones.     

Pulling CsI(Na) single crystals from melt by continuous method without plastic deformation

It is established that bromine impurity in CsI(Na) crystals not only facilitates the homogeneous incorporation of an activator into the lattice and prevents complex activator clusters from forming, but it also significantly hinders (at certain concentrations) the action of the primary and secondary dislocation slip systems. It is shown that the automatic pulling of large CsI-based crystals can be provided by the introduction of a single Br impurity into the charge; this impurity, to a large extent, strengthens only the top part of the crystal. The absence of plastic deformation in CsI-CsBr(Na) crystals with a diameter Ø300 mm and height h = 600 mm (grown by the continuous method) and Ø500 mm and h = 200 mm (grown by the automatic Kiropulos method) has been experimentally confirmed.     

Pyrazolo[1,5-a]pyrimidines. Identification of the privileged structure and combinatorial synthesis of 3-(hetero)arylpyrazolo[1,5-a]pyrimidine-6-carboxamides

The pyrazolo[1,5-a]pyrimidine class of compounds has been identified as a privileged structure for library synthesis on the basis of several key characteristics of the core molecule. A chemical set in excess of 400 compounds was synthesized to give 3,6,7-substituted pyrazolo[1,5-a]pyrimidinecarboxamides 9. To facilitate the rapid preparation of this library, a preparative strategy included the synthesis of activated p-nitrophenyl esters, followed by subsequent scavenging of the p-nitrophenol leaving group. Excess reagents were also removed using scavenging reagents that were found to be compatible with the synthetic methodology and that afforded target compounds in acceptable purity and yields.