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.

Ultrasonic-promoted three-component synthesis of some biologically active 1,2,5,6-tetrahydropyrimidines.

Multicomponent reactions and organic synthesis with ultrasonic activation have been used as key methods for the synthesis of tetrahydropyrimidine derivatives. The three-component condensation of 1,3-diarylprop-2-en-1-one with ammonia and aldehydes/acetone or N-substituted gamma-pyridones under ultrasonic irradiation was developed as a rapid and efficient solution-phase method for the high-yielding preparation of 2-aryl(hetaryl)-4,6-diaryl-1,2,5,6-tetrahydropyrimidines and 2,4-diaryl-1,5,9-triazaspiro[5.5]undec-1-enes. The described synthetic protocol provides rapid access to novel and diversely substituted tetrahydropyrimidines libraries. The simple, primary biological screening showed 98% of inhibitory activity against Mycobacterium tuberculosis for one of tetrahydropyrimidines synthesized.

Microwave-assisted three-component synthesis of 7-aryl-2-alkylthio-4,7-dihydro-1,2,4-triazolo[1,5-a]-pyrimidine-6-carboxamides and their selective reduction.

Multicomponent reactions (MCRs) and microwave-assisted organic synthesis (MAOS) have been used as key methods for the synthesis of fused dihydropyrimidine derivatives. The three-component condensation of 3-amino-5-alkylthio-1,2,4-triazoles with aromatic aldehydes and acetoacetamides under microwave irradiation was developed as a rapid and efficient solution-phase method for the high-yielding preparation of 7-aryl-2-alkylthio-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxamide libraries. In addition, the selective reduction of the formed dihydrotriazolopyrimidines to trans-trans-2-alkylthio-7-aryl-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxamides was established. The described synthetic protocols provide rapid access to novel and diversely substituted dihydroazolopyrimidine libraries.