Sergey M. Desenko

Tuning of chemo- and regioselectivities in multicomponent condensations of 5-aminopyrazoles, dimedone, and aldehydes.

Regio- and chemoselective multicomponent protocols for the synthesis of 1,4,6,7,8,9-hexahydro-1H-pyrazolo[3,4-b]quinolin-5-ones, 5,6,7,9-tetrahydropyrazolo[5,1-b]quinazolin-8-ones, and 5a-hydroxy-4,5,5a,6,7,8-hexahydropyrazolo[4,3-c]quinolizin-9-ones starting from 5-amino-3-phenylpyrazole, cyclic 1,3-dicarbonyl compounds and aromatic aldehydes are described. Whereas the three-component coupling in ethanol under reflux conditions provides mixtures of pyrazoloquinolinones and pyrazoloquinazolinones, the condensation can be successfully tuned toward the formation pyrazoloquinolinones (Hantzsch-type dihydropyridines) by performing the reaction at 150 degrees C in the presence of triethylamine base applying sealed vessel microwave or conventional heating. On the other hand, using sonication at room temperature under neutral conditions favors the formation of the isomeric pyrazoloquinazolinones (Biginelli-type dihydropyrimidines). These products are also obtained when the three-component condensation is executed in the presence of trimethylsilylchloride as reaction mediator at high temperatures. A third reaction pathway leading to pyrazoloquinolizinones in a ring-opening/recyclization sequence can be accessed by switching from triethylamine to a more nucleophilic base such as sodium ethoxide or potassium tert-butoxide. The reaction mechanism and intermediates leading to these three distinct tricyclic condensation products are discussed.

Aminoazoles as Key Reagents in Multicomponent Heterocyclizations

Because of the significant role in biological processes in living cells and the diverse types of physiological activities, heterocyclic compounds are in focus of intense investigations by academic and applied-oriented chemists. Considerably, a scientific renaissance of heterocycles during the last decades is closely related to the development of multicomponent approaches to their synthesis. Multicomponent methodology fundamentally different from two-component or sequential processes together with other innovative synthetic methods like microwave- and ultrasonic- assisted reactions offer some new possibilities in constructing heterocyclic systems with high level of molecular diversity and complexity. An overview of known multicomponent heterocyclizations using aminoazoles as a key reagent and their rich synthetic potential for obtaining five-, six-, and seven-membered heterocycles is presented. A special attention is paid to the tuning of chemo- and regio- and positional selectivity of some reactions as well as to the application of nonclassical activation methods based on microwave and ultrasonic irradiation.

Synthesis of partially hydrogenated 1,2,4-triazoloquinazolines by condensation of 3,5-diamino-1,2,4-triazole with aromatic aldehydes and dimedone

Three-component condensation of 3,5-diamino-1,2,4-triazole with aromatic aldehydes and dimedone in dimethylformamide gives 2-amino-5-aryl-8,8-dimethyl-5,6,7,8,9,10-hexahydro[1,2,4]triazolo[3,2-b]quinazolin-6-ones. The reaction of 3,5-diamino-1,2,4-triazole with dimedone in the absence of aldehyde involves dimethylformamide as one of the carbonyl components to afford 2-amino-8,8-dimethyl-6,7,8,9-tetrahydro[1,2,4]triazolo[2,3-a]quinazolin-6-one.

Multicomponent heterocyclization reactions with controlled selectivity (Review)

The review is devoted to the problem of controlling the selectivity of multicomponent heterocyclizations. Special attention has been paid to analysis of the literature of the last decade concerning the use of nonclassical methods of activating chemical processes, such as microwave and ultrasonic irradiation.

Dotting the i's in three-component Biginelli-like condensations using 3-amino-1,2,4-triazole as a 1,3-binucleophile

Alternative reaction pathways for Biginelli-like cyclocondensation reactions using 3-amino-1,2,4-triazole as a 1,3-binucleophile under different reaction conditions lead to several types of products. The literary data is generalized and discussed. Additional results going beyond the generalization are also revealed.

Rapid three-step one-pot microwave-assisted synthesis of 2,5-dioxo-1,2,5,6,7,8-hexahydro-3-quinolinecarbonitrile library.

Many well-known drugs contain 2-pyridone and 2-quinolone scaffolds. In the current paper, a one-pot three-step microwave-assisted method for the synthesis of N1-substituted 2,5-dioxo-1,2,5,6,7,8-hexahydro-3-quinolinecarbonitrile derivatives was developed. Employing this protocol, we quickly generated 105 compounds library from 1,3-cyclohexanediones, dimethylformamide dimethylacetal, and various cyanacetamides.

Diversity oriented heterocyclizations of pyruvic acids, aldehydes and 5-amino-N -aryl-1H -pyrazole-4-carboxamides: catalytic and temperature control of chemoselectivity

Heterocyclization reactions of pyruvic acids, aromatic aldehydes and 5-amino-N-aryl-1H-pyrazole-4-carboxamides yielding four different types of final compounds are described. The reactions involving arylidenpyruvic acids lead with high degree of selectivity to either 4,7-dihydropyrazolo[1,5-a]pyrimidine-5-carboxylic acids or 5-[(2-oxo-2,5-dihydrofuran-3-yl)amino]-1H-pyrazoles, depending on the catalyst type or temperature regime. The interactions based on arylpyruvic acids can take place under kinetic or thermodynamic control producing 7-hydroxy-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-7-carboxylic acids or 3-hydroxy-1-(1H-pyrazol-5-yl)-1,5-dihydro-2H-pyrrol-2-ones, respectively.

An easy access to 2-Amino-5,6-dihydro-3H-pyrimidin-4-one building blocks: The reaction under conventional and microwave conditions

SummaryA new one-stage fast multicomponent synthesis of title compounds leads to products in 21–55% isolated yields under both conventional and microwave conditions. The primary amino group in the building blocks can be easily acylated by various usual electophilic agents that can be utilized in the synthesis of diverse heterocylic compounds libraries.

Diversification of a thieno[2,3-d]pyrimidin-4-one scaffold via regioselective alkylation reactions.

The 2-aryl-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-ones and 2-aryl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-ones have been diversified by alkylation reactions, applying benzylchlorides and N-substituted 2-chloroacetamides as alkylating agents. Under the found uniform conditions the substitution direction does not depend on the structure of the alkylating agent and gives monoalkylated products in high yields with simple workup. The alkylation of the 2,3-dihydropyrimidin-4(1H)-one derivatives proceeds onto the N1-position; however, in the case of pyrimidin-4(3H)-ones the O-alkylated products are formed selectively. An alternative strategy for the synthesis of the N1-benzyl-2,3-dihydropyrimidin-4(1H)-one derivatives is also developed. It applies the redaction of N2-substituted Gewalds amides with aromatic aldehydes and allows simple introduction of various substituents in the final molecule.

Multicomponent Cyclocondensations of b-Ketosulfones with Aldehydes and Aminoazole Building Blocks

The multicomponent reaction of methylsulfonylacetone (or α-methylsulfonylacetophenone) with aromatic aldehydes and aminoazoles (or urea) under microwave irradiation to yield 5,8-dihydroimidazolo[1,2-a]pyrimidines and 4,7-dihydro[l,2,4]triazolo[l,5-a]pyrimidines was studied. The influence of the type of aminoazole building block on the reactivity was established. In addition, an unusual reaction pathway for the Biginelli-type condensation of methylsulfonylacetone with aldehydes and urea leading to non-classical Hantzsch-type dihydropyridines was found.