Intensification of ion exchange desorption of thiamine diphosphate by low-powered ultrasound.

The process of ultrasound-assisted ion-exchange desorption of cocarboxylase (thiamine diphosphate (TDP)) from a strong acidic cation resin was studied. Kinetics studies revealed that ultrasound accelerates TDP desorption by 3 times. The optimal desorption parameters, viz. US power input, sonication time, eluent/resin ratio and the eluent (ammonium acetate buffer) concentration were established which were 15mW/cm3, 20min, 1:1 and 1M, respectively. The resin stability studies showed that the optimal ultrasonic power was less by the order than the resin degradation threshold which ensures durable and efficient resin exploitation during production. The resin sorption capacity remained unchanged even after 20 cycles of TDP sorption, ultrasonic desorption and resin regeneration. The recovery ratio of TDP was shown to increase non-linearly with decreasing the resin saturation factor, which can be attributed to diffusion limitations occurring during desorption. The optimal resin loading corresponding to more than 90 per cent of TDP recovery was found to be at the level of 10 per cent of the maximal sorption capacity. The study revealed 4-5-fold increase in concentrations of the recovered solutions, which together with process times shortening should result in considerable energy saving in downstream operations on production scale.

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized.

The well-known aminoazoles, 3-amino-5-methylisoxazole and 5-amino-N-aryl-1H-pyrazole-4-carboxamides, were studied as an amine component in Ugi and Groebke-Blackburn-Bienaymé multicomponent reactions. The first example of an application of aminoazoles in an Ugi four-component reaction was discovered and novel features of a Groebke-Blackburn-Bienaymé cyclocondensation are established and discussed. The heterocycles obtained were evaluated for their antibacterial activity and several of them demonstrated a weak antimicrobial effect, but for most of the compounds a 30-50% increase in biomass of Gram-positive strains (mainly B. subtilis) compared to control was observed.

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde.

The switchable three-component reactions of 5-amino-3-methylisoxazole, salicylaldehyde and N-aryl-3-oxobutanamides under different conditions were studied and discussed. The unexpected influence of the aryl substituent in N-aryl-3-oxobutanamides on the behavior of the reaction was discovered. The key influence of ultrasonication and Lewis acid catalysts led to an established protocol to selectively obtain two or three types of heterocyclic scaffolds depending on the substituent in the N-aryl moiety.

Features of the behavior of 4-amino-5-carboxamido-1,2,3-triazole in multicomponent heterocyclizations with carbonyl compounds.

Multicomponent reactions involving polyfunctional 4-amino-5-carboxamido-1,2,3-triazole and cyclic carbonyl-containing CH-acids were studied under conventional thermal heating, microwave and ultrasonic irradiation. The features of the reactions studied were discussed and the optimized procedures for the synthesis of final triazolopyrimidines were elaborated. In contrast to the similar MCRs of numerous other aminoazoles, a change of direction of the heterocyclizations in the case of 4-amino-5-carboxamido-1,2,3-triazole was not observed when microwave or thermal heating was substituted by ultrasonication at ambient temperature.

High regioselective ultrasonic-assisted synthesis of 2,7-diaryl-4,7-dihydropyrazolo[1,5-a]pyrimidine-5-carboxylic acids.

New and high regioselective method of the synthesis of 2,7-diaryl-4,7-dihydropyrazolo[1,5-a]pyrimidine-5-carboxylic acids by reaction of 3-aryl-5-aminopyrazoles with arylidenpyruvic acid at room temperature under ultrasonication was developed and discussed.

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.

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.

One-pot, multicomponent route to pyrazoloquinolizinones.

[reaction: see text] An efficient synthesis of 5a-hydroxy-4,5,5a,6,7,8-hexahydropyrazolo[4,3-c]quinolizin-9-ones based on the three-component condensation of 5-aminopyrazoles, aromatic aldehydes, and cyclic 1,3-diketones is described. The multicomponent reaction is performed under strongly basic conditions applying controlled microwave heating in a sealed vessel and involves an unusual base-mediated ring-opening/recyclization of the cyclic 1,3-diketone moiety.

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.