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13 results on '"Drev, Miha"'

1. 2-Bromopyridines as Versatile Synthons for Heteroarylated 2-Pyridones via Ru(II)-Mediated Domino C–O/C–N/C–C Bond Formation Reactions.

Author

Drev, Miha, Brodnik, Helena, Grošelj, Uroš, Perdih, Franc, Svete, Jurij, Štefane, Bogdan, and Požgan, Franc

Subjects
*RUTHENIUM, *HETEROCYCLIC compounds, *CATALYSIS, *ATOMS, *OXYGEN
Abstract

A novel methodology for the synthesis of 2-pyridones bearing a 2-pyridyl group on nitrogen and carbon atoms, starting from 2-bromopyridines, was developed employing a simple Ru(II)–KOPiv–Na2CO3 catalytic system. Unsubstituted 2-bromopyridine was successfully converted to the penta-heteroarylated 2-pyridone product using this method. Preliminary mechanistic studies revealed a possible synthetic pathway leading to the multi-heteroarylated 2-pyridone products, involving consecutive oxygen incorporation, a Buchwald–Hartwig-type reaction, and C–H bond activation. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Catalytic heteroarylation as synthetic approach towards polydentate ligands

Author

Drev, Miha and Požgan, Franc

Subjects
complexes, pyridones, rutenij, water, hexaheteroarylbenzene, voda, heksa(hetero)arilbenzeni, mikrovalovi, ruthenium, piridoni, microwaves, kompleksi
Abstract

In the first part, an efficient (hetero)arylation of ortho-C–H bonds of the benzene ring of 2-arylpyrimidines is achieved by Ru(II)–carboxylate-catalyzed reaction with (hetero)aryl bromides in water under microwave irradiation. This ''green'' methodology provides a series of polyconjugated pyrimidines with high site-selectivity. As established from Hammett plots, electron-withdrawing groups on phenyl ring of the pyrimidine substrates facilitate the arylation, while both electron-withdrawing and electron-donating groups on the aryl bromides assure a faster reaction. Applicability of heteroaryl-pyrimidines was demonstrated by their ligation to ruthenium or palladium center. In the second part, a series of hexa(heteroaryl)benzenes were synthesized by the Ru(II)–carboxylate-catalyzed multiple C–H activation of benzenes carrying pyridyl, pyrimidyl, or pyrazolyl directing groups using N-heteroaryl bromides as coupling partners. The reactions proceeded with high selectivity under microwave irradiation in water. Iterative penta-arylation could be implemented via sequential activation of C–H bonds of generated intermediates by cascade chelation assistance of in situ installed pyridyl groups. In the third part, the preliminary study on N-pyridylpyridin-2-one formation from substituted 2-bromopyridines was obtained. The pyridones were formed in the presence of Ru(II)-pivalate-Na2CO3 catalytic system. The study suggested that oxygen for 2-pyridone formation comes from pivalate which is regenerated with carbonate during the catalytic cycle. In the fourth part, the synthesized multiheteroaryl-substituted benzenes were used as ligands in coordination to selected transition metals (Ru, Pd and Ag) to obtain multinuclear complexes. Novel seven-membered bidentate Ru(II) complexes with one or two metal centres were prepared. The strategy was also employed in coordination of two Pd(II) and two Pt(II) cations as well as mixed Ru(II)-Pd(II) and Ru(II)-Pt(II) complexes. The poly(hetero)arylated benzenes were further used as ligands in coordination with Ag(I) ions, to obtain tetra- and pentanuclear complexes. The Ag(I) ions are in square or pentagon orientation, with F- ion in the centre of complex, between two hexa-coordinating ligands. V prvem delu smo razvili učinkovito metodo (hetero)ariliranja orto-C–H vezi na benzenovem obroču 2-arilpirimidina. Z Ru(II)–karboksilatom katalizirane reakcije s (hetero)aril bromidi smo izvajali v vodi pod pogoji mikrovalovnega segrevanja. Na ta način smo po načelih zelene kemije in z visoko regioselektivnostjo pripravili serijo polikonjugiranih pirimidinov. Mehanistične študije na podlagi Hammettove korelacije nakazujejo, da elektronprivlačne skupine na pirimidinskem substratu pospešujejo ariliranje, medtem ko skupine na aril bromidih, tako elektronprivlačne kakor tudi elektrondonorske, zagotavljajo hitrejše reakcije. Prikazali smo tudi koordinacijske lastnosti heteroaril-pirimidinov pri koordinaciji rutenija(II). V drugem delu smo pripravili serijo heksa(heteroaril)benzenov z uporabo Ru(II)-karboksilatnega katalitskega sistema. Reakcije večkratne C–H aktivacije z N-heteroaril bromidi so potekale regioselektivno na benzenovih obročih, ki so vsebovali piridilnske, pirimidilnske ali pirazolnske usmerjajoče skupine. Reakcije smo izvajali v vodi pod pogoji mikrovalovnega segrevanja. Zaporedno penta-ariliranje poteka preko sekvenčne aktivacije C–H vezi, kjer vsaka nova uvedena skupina usmerja nadaljnjo C–H aktivacijo. V tretjem delu smo raziskovali nastanek N-piridilpiridin-2-onov iz različno substituiranih 2-bromopiridinov. Preliminarne študije potrjujejo, da je za nastanek piridona ključna sinergija Ru(II) katalizatorja, kalijevega pivalata in Na2CO3. Rezultati eksperimentov z izotopsko označenim kisikom nakazujejo, da kisik pri tvorbi piridona najverjetneje pride iz pivalata, ki se tekom katalitskega cikla regenerira s karbonatom. V četrtem delu smo pripravljene polidentatne ligande uporabili v koordinaciji izbranih kovin prehoda (Ru, Pd, Pt and Ag). Na ta način smo pripravili nove bidentatne Ru(II) komplekse s sedemčlenskim kelatnim obročem z eno ali dvema koordiniranima kovinama. Metodo koordinacije dveh kovin smo nato aplicirali še na Pd(II) in Pt(II), kakor tudi za pripravo mešanih Ru(II)-Pd(II) in Ru(II)-Pt(II) kompleksov. S koordinacijo Ag(I) ionov na polidentate smo pripravili štiri- in petjederne komplekse, kjer so Ag(I) ioni med dvema ligandoma. Na sredini kompleksa je F- ion, ki je koordiniran na štiri Ag(I) ione.

Published
2020

11. Transformations of β-aryl- N-Cbz- α, β-didehydro- α-amino esters with hydrazine hydrate.

Author

Drev, Miha, Grošelj, Uroš, and Svete, Jurij

Subjects
*RING formation (Chemistry), *AMINO acids, *HYDANTOIN, *HYDRATES, *REACTION time
Abstract

Cyclizations of Cbz-protected α, β-didehydro- β-arylalanine esters 1 with excess hydrazine hydrate afforded mixtures of the expected 3-pyrazolidinones 2 and the unexpected 1-amino-5-benzylidenehydantoins 6 and N-Cbz- β-arylalanine hydrazides 7. Presumably, the pyrazolidinones 2 and hydantoins 6 are formed as primary products via competitive 1,2- and 1,4-addition of hydrazine hydrate followed by cyclization, whereas β-arylalanine hydrazides 7 are formed as secondary products via reductive cleavage of the C(5)-N(1) bond in pyrazolidinones 2. The overall selectivity depends on the reaction time and on the β-substituent in the starting dehydroalanine ester 1. [ABSTRACT FROM AUTHOR]

Published
2016
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12. Stability and Degradation Pathways of N-Nitroso-Hydrochlorothiazide and the Corresponding Aryl Diazonium Ion

Author

Grahek, Rok, Drev, Miha, Zupančič, Borut, Hren, Jure, Ošlaj, Matej, Bastarda, Andrej, Kocijan, Andrej, and Časar, Zdenko

Abstract

Despite the fact that it was put on the market more than 60 years ago, hydrochlorothiazide (HCT) is still one of the most important antihypertensive drugs. Due to its chemical structure, which contains the secondary aryl-alkyl-amino moiety, it is vulnerable to the formation of N-nitrosamine drug substance-related impurity (NDSRI) N-nitroso-hydrochlorothiazide (NO-HCT). In our study, we reveal that NO-HCT degrades rapidly at pH values 6 to 8. The main degradation products identified are formaldehyde, thiatriazine, and aminobenzenesulfonic acid derivative. Interestingly, degradation of NO-HCT at pH values from 5 to 1 is significantly slower and provides a different impurity profile when compared to the profile generated between pH 6 and 8. Specifically, between pH 1 and 5, HCT is observed as one of the key degradation products of NO-HCT in addition to formaldehyde and aminobenzenesulfonic acid. Moreover, at pH 1, the aminobenzenesulfonic acid derivative is transformed to the corresponding diazonium salt in approximately 3% yield with the nitrosyl cation, which is released during the decomposition of NO-HCT to HCT. This diazonium is highly unstable above pH 5. To verify that degradation of NO-HCT does not produce the corresponding diazonium salt that could be formed via metabolic activation of NO-HCT, this diazonium salt and its hydrolytic and reduction degradation products were synthesized and used as standards for the identification of species formed during the degradation of NO-HCT. This enabled us to confirm that the corresponding aryl diazonium salt, which would be obtained from metabolic activation of NO-HCT, is not observed in the NO-HCT degradation pathway. Our study also demonstrates that this diazonium salt is stable only in the presence of a large excess of strong mineral acid under anhydrous conditions. In the presence of water, it is instantaneously converted to an aminobenzenesulfonic acid derivative. These findings suggest that the NO-HCT should not be considered as a typical compound belonging to the cohort of the concern.

Published
2023
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13. Synthesis of 3D-Rich Heterocycles: Hexahydropyrazolo[1,5-a]pyridin-2(1H)-ones and Octahydro-2H-2a,2a 1 -diazacyclopenta[cd]inden-2-ones.

Author

Pušavec Kirar E, Drev M, Mirnik J, Grošelj U, Golobič A, Dahmann G, Požgan F, Štefane B, and Svete J

Abstract

Two cyclic azomethine imines, 7-methyl- and 7-phenyl-2-oxo-Δ 7 -hexahydropyrazolo[1,5-a]pyridin-8-ium-1-ide, were prepared in seven steps from the respective commercially available δ-keto acids. The addition of Grignard reagents followed by N-alkylation at position 1 afforded the 1,7,7-trisubstituted hexahydropyrazolo[1,5-a]pyridin-2(1H)-ones, whereas 1,3-dipolar cycloadditions of these dipoles to typical acetylenic and olefinic dipolarophiles gave 4a-substituted 2a,2a 1 -diazacyclopenta[cd]indene derivatives as the first representatives of a novel heterocyclic system. Regio- and stereoselectivity as well as the mechanism of these [3 + 2]-cycloadditions were evaluated using computational and experimental methods. The data obtained were in agreement with the polar concerted cycloaddition mechanism via the energetically favorable syn/endo-transition states.

Published
2016
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