József Nagy | Budapest University of Technology and Economics (original) (raw)
Papers by József Nagy
Periodica Polytechnica Chemical Engineering
The formal [2+2] cycloaddition of ketenes and imines, also known as Staudinger synthesis, is a fa... more The formal [2+2] cycloaddition of ketenes and imines, also known as Staudinger synthesis, is a facile method for the synthesis of biologically important β-lactam derivatives. In this paper two previously reported stereoselective reactions were investigated with computational methods. Our computations support experimental data that a chiral imine, derived from d-glyceraldehyde reacting with ketenes, yields almost exclusively one out of the possible four diastereomers. The reaction proceeds stepwise, first addition of the imine to the ketene yields an intermediate, then the product is formed in a conrotatory electrocyclization. Results indicate that the electrostatic repulsion of the chiral auxiliary group is the main factor of the stereoselectivity, but solvent and substituent effects are not negligible. Calculations were performed at M06-2X/6-31+G** level of theory combined with IEF-PCM solvation, in common solvents such as toluene, THF, dichloromethane, acetonitrile and water. Thes...
Molecules (Basel, Switzerland), Jan 19, 2017
The chemistry of the 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (1,3-diazaoxindole) compound fa... more The chemistry of the 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (1,3-diazaoxindole) compound family, possessing a drug-like scaffold, is unexplored. In this study, the alkylation reactions of N(7)-unsubstituted 5-isopropyl-1,3-diazaoxindoles bearing various substituents at the C(2) position have been investigated. The starting compounds were synthesized from the C(5)-unsubstituted parent compounds by condensation with acetone and subsequent catalytic reduction of the 5-isopropylidene moiety. Alkylation of the thus obtained 5-isopropyl derivatives with methyl iodide or benzyl bromide in the presence of a large excess of sodium hydroxide led to 5,7-disubstituted derivatives. Use of butyllithium as the base rendered alkylation in the C(5) position possible with reasonable selectivity, without affecting the N(7) atom. During the study on the alkylation reactions, some interesting by-products were also isolated and characterized.
Chirality, Jan 26, 2017
New enantiopure dimethyl-substituted acridino-18-crown-6 and acridino-21-crown-7 ethers containin... more New enantiopure dimethyl-substituted acridino-18-crown-6 and acridino-21-crown-7 ethers containing a carboxyl group at position 9 of the acridine ring [(S,S)-8, (S,S)-9, (R,R)-10] were synthesized. The pKa values of the new crown ethers [(S,S)-8, (S,S)-9, (R,R)-10] and of an earlier reported macrocycle [(R,R)-2] were determined by UV-pH titrations. Crown ether (S,S)-8 was attached to silica gel by covalent bonds and the enantiomeric separation ability of the newly prepared chiral stationary phase [(S,S)-CSP-12] was studied by high-performance liquid chromatography (HPLC). Homochiral preference was observed and the best separation was achieved for the enantiomers of 1-NEA. Ligands (S,S)-9 and (R,R)-10 are precursors of enantioselective sensor and selector molecules for the enantiomers of protonated primary amines, amino acids, and their derivatives.
Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2016
Advanced Synthesis & Catalysis, 2016
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, Jan 4, 2015
B3LYP is one of the most widely used functional for the prediction of electronic circular dichroi... more B3LYP is one of the most widely used functional for the prediction of electronic circular dichroism spectra, however if the studied molecule contains aromatic nitro group computations may fail to produce reliable results. A test set of molecules of known stereochemistry were synthesized to study this phenomenon in detail. Spectra were computed by B3LYP and CAM-B3LYP functionals with 6-311++G(2d,2p) basis set. It was found that the range separated CAM-B3LYP gives better predictions than B3LYP for all test molecules. Fragment population analysis revealed that the nitro groups form highly localized molecule orbitals but the exact composition depends on the functional. CAM-B3LYP allows sufficient spatial overlap between the nitro group and distant parts of the molecule, which is necessary for the accurate description of excited states especially for charge transfer states. This phenomenon and the synthesized test molecules can be used to benchmark theoretical methods as well as to help ...
1. L- és D-treoninból kiindulva megoldottuk a célul kitűzött 4 diasztereomer transz-7-(1-hidroxie... more 1. L- és D-treoninból kiindulva megoldottuk a célul kitűzött 4 diasztereomer transz-7-(1-hidroxietil)-2-izoxacefém-4-karbonsavak előállítását, melyek közül az egyik konfigurációja (alfaR,6S,7S) megegyezik a Tienamicin megfelelő szénatomjainak konfigurációjával. Ezeket a vegyületeket biológiai hatásvizsgálat céljából két laboratóriumnak megküldtük. 2. Megoldottuk a cisz-acetoxi-észterek redukcióját a megfelelő diollá. Az ebből egyszerűen képezhető dimezil vegyület gyűrűzárásával azonban nem jutottunk a kívánt 7-(1-hidroxietil)-2-izoxacefém vegyülethez. Kísérleteket végeztünk a primer és szekunder OH csoport megkülönböztetésére a cukorkémiában ismeretes tritilezés/acetilezés/detritilezés módszerével. A módszer a két OH csoport térközelsége miatt nem hozta meg a kívánt eredményt, intramolekuláris átacetileződés játszódott le. Ezért új stratégiát kerestünk a cisz gyűrűannelációjú 2-izoxacefémek előállítására, megváltoztatva a korábban alkalmazott védőcsoportokat. Dibenzil-malonátból kii...
Tetrahedron: Asymmetry, 2015
ABSTRACT
Integrating Stereoselective and Environmentally Friendly Reactions, 2014
ABSTRACT
Journal für praktische Chemie, 2000
ABSTRACT
![Research paper thumbnail of Synthesis of pure methyl [(2S,3R,αR)-1-(3-bromo-4-methoxyphenyl)-3-(α-acetoxy)ethyl-4-oxoazetidin-2-carboxylate] and its enantiomer](https://attachments.academia-assets.com/71080326/thumbnails/1.jpg)
](Tetrahedron: Asymmetry, 2001
Synthesis of key intermediates leading to 2-iso-oxacephems was carried out starting from Land D-t... more Synthesis of key intermediates leading to 2-iso-oxacephems was carried out starting from Land D-threonine. As predicted in our previous paper (Tetrahedron Lett. 1995, 36, 8303-8306) all diastereomers of 2-iso-oxacephems can be prepared from the appropriate enantiomers of the amino acid threonine. The absolute configuration of the 2,3-and a-carbon atoms in the b-lactam structure was determined by X-ray crystallographic studies.
Tetrahedron: Asymmetry, 2006
All four trans-stereoisomers of 7-(1-hydroxyethyl)-2-iso-oxacephem-4-carboxylic acids, which are ... more All four trans-stereoisomers of 7-(1-hydroxyethyl)-2-iso-oxacephem-4-carboxylic acids, which are the 2-iso-oxacephem analogues of Thienamycin, have been synthesized. (αR,6R,7R)- and (αS,6S,7S)-7-(1-hydroxyethyl)-3-methyl-2-iso-oxacephem-4-carboxylic acids have been prepared starting from l- and d-threonine, the configuration at the α-position was inverted by using Mitsunobu reactions providing the (αS,6R,7R)- and (αR,6S,7S)-diastereomers of the compounds above. A synthetic route to the cis-annelated analogues was also worked out.
Organic & Biomolecular Chemistry, 2011
The carbene concentration in 1-ethyl-3-methylimidazoliumacetate ionic liquid is sufficiently high... more The carbene concentration in 1-ethyl-3-methylimidazoliumacetate ionic liquid is sufficiently high to act as a catalyst in benzoin condensation, hydroacylation and also in oxidation of an alcohol by using CO 2 and air. This observation reveals the potential of ionic liquid organocatalysts, uniting the beneficial properties of these two families of compounds. Ionic liquids 1 (ILs) exhibit an outstanding variety of advantageous properties, such as high stability, non-flammability, low volatility and unique solution features. 1o-r They have successfully been used as solvents for many catalytic reactions, 1j,k,o,p either organometallic or purely organic (organocatalytic). Some of these syntheses could not be performed in any of the classic molecular solvents. 1j-k Although in most of these reactions the IL is merely the solvent, there are a few reports 2 showing that imidazolium based ionic liquids can be used as precatalysts for N-heterocyclic carbene (NHC) catalyzed 3 reactions, whereby the catalyst can be obtained by deprotonation. However, while triazolium and thiazolium salts can be deprotonated relatively easily 4 (note also the biological activity 5 of vitamin B1), the most robust IL cations, imidazolium derivatives, need strong deprotonating agents (e.g. DBU 2b or NaOMe with ultrasonic activation 2e). In recent studies 6 electrolytic reduction of the imidazolium salt to the carbene has been reported, 6a and the carbene produced this way has been shown to act as a catalyst in various reactions, 6 including the benzoin condensation. 3a-d,5,7 In our previous study 8 we have shown that with basic anions (e.g. acetate) imidazolium salts can be deprotonated in the gaseous phase resulting in carbenes (Fig. 1). In the bulk of the liquid phase, however, the interaction with the surrounding charged particles stabilizes the ionic form. 8 Nevertheless, the carbene could be trapped by palladium(II) acetate from imidazoliumbased ILs 2c-d including the acetate, 9a or by elemental chalcogens 9a from 1-ethyl-3-methylimidazolium acetate (EMIM-Ac) forming imidazole-2-chalcogenones. 9a Surprisingly, EMIM-Ac in a 1 : 1
Monatshefte f�r Chemie / Chemical Monthly, 2004
Journal of Molecular Catalysis B: Enzymatic, 2013
The effect of temperature on enantiomeric ratio (E) and specific reaction rate (r flow) in the co... more The effect of temperature on enantiomeric ratio (E) and specific reaction rate (r flow) in the continuousflow mode acetylation of (±)-1-phenylethanamine (rac-1a), (±)-4-phenylbutan-2-amine (rac-1b) and (±)-1,2,3,4-tetrahydro-1-naphthalenamine (rac-1c) by variously immobilized Candida antarctica lipase B biocatalysts was studied in the 0-70 • C range. In the continuous-flow kinetic resolutions with differently immobilized CaLB biocatalysts, the character of temperature effect depended significantly both on the substrate and on the mode of immobilization. Alteration of E in the kinetic resolutions of three differently flexible amines rac-1a-c as a function of temperature was rationalized by the various flexibility of the lipase in its different forms. Our results indicated that the optimal method of immobilization depended both on the nature of the substrate and the reaction conditions.
European Journal of Organic Chemistry, 1999
ABSTRACT
Composites Part A: Applied Science and Manufacturing, 1998
Interfacial interactions significantly influence the properties of particulate filled polymers. T... more Interfacial interactions significantly influence the properties of particulate filled polymers. The adhesion between the particles and the polymer matrix depends on the size (area) of the interface and the strength of the interaction. While the former quantity is related to the specific surface area of the filler, the strength of the interaction can be modified by its surface treatment. In the current experiments polypropylene composites were prepared which contained different amounts of filler treated with eight functional trialkoxy silane coupling agents and the routinely used stearic acid, for comparison. Tensile properties of the composites were determined and the effect of interfacial interaction was evaluated by semi-empirical equations developed previously. Significant difference was detected in the effect of the various silane coupling agents. Amino functional silanes increase the strength of the interaction considerably. The other coupling agents reduce the surface tension of the filler, which leads to a decrease in the reversible work of adhesion between the filler and the polymer. These changes result in a decrease in the tensile strength of the composite. The results also prove the validity of the model equations applied. Parameter B, a measure of the strength of the interaction, was calculated for each silane coupling agent thus quantitatively characterizing their effectiveness.
Periodica Polytechnica Chemical Engineering
The formal [2+2] cycloaddition of ketenes and imines, also known as Staudinger synthesis, is a fa... more The formal [2+2] cycloaddition of ketenes and imines, also known as Staudinger synthesis, is a facile method for the synthesis of biologically important β-lactam derivatives. In this paper two previously reported stereoselective reactions were investigated with computational methods. Our computations support experimental data that a chiral imine, derived from d-glyceraldehyde reacting with ketenes, yields almost exclusively one out of the possible four diastereomers. The reaction proceeds stepwise, first addition of the imine to the ketene yields an intermediate, then the product is formed in a conrotatory electrocyclization. Results indicate that the electrostatic repulsion of the chiral auxiliary group is the main factor of the stereoselectivity, but solvent and substituent effects are not negligible. Calculations were performed at M06-2X/6-31+G** level of theory combined with IEF-PCM solvation, in common solvents such as toluene, THF, dichloromethane, acetonitrile and water. Thes...
Molecules (Basel, Switzerland), Jan 19, 2017
The chemistry of the 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (1,3-diazaoxindole) compound fa... more The chemistry of the 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (1,3-diazaoxindole) compound family, possessing a drug-like scaffold, is unexplored. In this study, the alkylation reactions of N(7)-unsubstituted 5-isopropyl-1,3-diazaoxindoles bearing various substituents at the C(2) position have been investigated. The starting compounds were synthesized from the C(5)-unsubstituted parent compounds by condensation with acetone and subsequent catalytic reduction of the 5-isopropylidene moiety. Alkylation of the thus obtained 5-isopropyl derivatives with methyl iodide or benzyl bromide in the presence of a large excess of sodium hydroxide led to 5,7-disubstituted derivatives. Use of butyllithium as the base rendered alkylation in the C(5) position possible with reasonable selectivity, without affecting the N(7) atom. During the study on the alkylation reactions, some interesting by-products were also isolated and characterized.
Chirality, Jan 26, 2017
New enantiopure dimethyl-substituted acridino-18-crown-6 and acridino-21-crown-7 ethers containin... more New enantiopure dimethyl-substituted acridino-18-crown-6 and acridino-21-crown-7 ethers containing a carboxyl group at position 9 of the acridine ring [(S,S)-8, (S,S)-9, (R,R)-10] were synthesized. The pKa values of the new crown ethers [(S,S)-8, (S,S)-9, (R,R)-10] and of an earlier reported macrocycle [(R,R)-2] were determined by UV-pH titrations. Crown ether (S,S)-8 was attached to silica gel by covalent bonds and the enantiomeric separation ability of the newly prepared chiral stationary phase [(S,S)-CSP-12] was studied by high-performance liquid chromatography (HPLC). Homochiral preference was observed and the best separation was achieved for the enantiomers of 1-NEA. Ligands (S,S)-9 and (R,R)-10 are precursors of enantioselective sensor and selector molecules for the enantiomers of protonated primary amines, amino acids, and their derivatives.
Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2016
Advanced Synthesis & Catalysis, 2016
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, Jan 4, 2015
B3LYP is one of the most widely used functional for the prediction of electronic circular dichroi... more B3LYP is one of the most widely used functional for the prediction of electronic circular dichroism spectra, however if the studied molecule contains aromatic nitro group computations may fail to produce reliable results. A test set of molecules of known stereochemistry were synthesized to study this phenomenon in detail. Spectra were computed by B3LYP and CAM-B3LYP functionals with 6-311++G(2d,2p) basis set. It was found that the range separated CAM-B3LYP gives better predictions than B3LYP for all test molecules. Fragment population analysis revealed that the nitro groups form highly localized molecule orbitals but the exact composition depends on the functional. CAM-B3LYP allows sufficient spatial overlap between the nitro group and distant parts of the molecule, which is necessary for the accurate description of excited states especially for charge transfer states. This phenomenon and the synthesized test molecules can be used to benchmark theoretical methods as well as to help ...
1. L- és D-treoninból kiindulva megoldottuk a célul kitűzött 4 diasztereomer transz-7-(1-hidroxie... more 1. L- és D-treoninból kiindulva megoldottuk a célul kitűzött 4 diasztereomer transz-7-(1-hidroxietil)-2-izoxacefém-4-karbonsavak előállítását, melyek közül az egyik konfigurációja (alfaR,6S,7S) megegyezik a Tienamicin megfelelő szénatomjainak konfigurációjával. Ezeket a vegyületeket biológiai hatásvizsgálat céljából két laboratóriumnak megküldtük. 2. Megoldottuk a cisz-acetoxi-észterek redukcióját a megfelelő diollá. Az ebből egyszerűen képezhető dimezil vegyület gyűrűzárásával azonban nem jutottunk a kívánt 7-(1-hidroxietil)-2-izoxacefém vegyülethez. Kísérleteket végeztünk a primer és szekunder OH csoport megkülönböztetésére a cukorkémiában ismeretes tritilezés/acetilezés/detritilezés módszerével. A módszer a két OH csoport térközelsége miatt nem hozta meg a kívánt eredményt, intramolekuláris átacetileződés játszódott le. Ezért új stratégiát kerestünk a cisz gyűrűannelációjú 2-izoxacefémek előállítására, megváltoztatva a korábban alkalmazott védőcsoportokat. Dibenzil-malonátból kii...
Tetrahedron: Asymmetry, 2015
ABSTRACT
Integrating Stereoselective and Environmentally Friendly Reactions, 2014
ABSTRACT
Journal für praktische Chemie, 2000
ABSTRACT
Tetrahedron: Asymmetry, 2001
Synthesis of key intermediates leading to 2-iso-oxacephems was carried out starting from Land D-t... more Synthesis of key intermediates leading to 2-iso-oxacephems was carried out starting from Land D-threonine. As predicted in our previous paper (Tetrahedron Lett. 1995, 36, 8303-8306) all diastereomers of 2-iso-oxacephems can be prepared from the appropriate enantiomers of the amino acid threonine. The absolute configuration of the 2,3-and a-carbon atoms in the b-lactam structure was determined by X-ray crystallographic studies.
Tetrahedron: Asymmetry, 2006
All four trans-stereoisomers of 7-(1-hydroxyethyl)-2-iso-oxacephem-4-carboxylic acids, which are ... more All four trans-stereoisomers of 7-(1-hydroxyethyl)-2-iso-oxacephem-4-carboxylic acids, which are the 2-iso-oxacephem analogues of Thienamycin, have been synthesized. (αR,6R,7R)- and (αS,6S,7S)-7-(1-hydroxyethyl)-3-methyl-2-iso-oxacephem-4-carboxylic acids have been prepared starting from l- and d-threonine, the configuration at the α-position was inverted by using Mitsunobu reactions providing the (αS,6R,7R)- and (αR,6S,7S)-diastereomers of the compounds above. A synthetic route to the cis-annelated analogues was also worked out.
Organic & Biomolecular Chemistry, 2011
The carbene concentration in 1-ethyl-3-methylimidazoliumacetate ionic liquid is sufficiently high... more The carbene concentration in 1-ethyl-3-methylimidazoliumacetate ionic liquid is sufficiently high to act as a catalyst in benzoin condensation, hydroacylation and also in oxidation of an alcohol by using CO 2 and air. This observation reveals the potential of ionic liquid organocatalysts, uniting the beneficial properties of these two families of compounds. Ionic liquids 1 (ILs) exhibit an outstanding variety of advantageous properties, such as high stability, non-flammability, low volatility and unique solution features. 1o-r They have successfully been used as solvents for many catalytic reactions, 1j,k,o,p either organometallic or purely organic (organocatalytic). Some of these syntheses could not be performed in any of the classic molecular solvents. 1j-k Although in most of these reactions the IL is merely the solvent, there are a few reports 2 showing that imidazolium based ionic liquids can be used as precatalysts for N-heterocyclic carbene (NHC) catalyzed 3 reactions, whereby the catalyst can be obtained by deprotonation. However, while triazolium and thiazolium salts can be deprotonated relatively easily 4 (note also the biological activity 5 of vitamin B1), the most robust IL cations, imidazolium derivatives, need strong deprotonating agents (e.g. DBU 2b or NaOMe with ultrasonic activation 2e). In recent studies 6 electrolytic reduction of the imidazolium salt to the carbene has been reported, 6a and the carbene produced this way has been shown to act as a catalyst in various reactions, 6 including the benzoin condensation. 3a-d,5,7 In our previous study 8 we have shown that with basic anions (e.g. acetate) imidazolium salts can be deprotonated in the gaseous phase resulting in carbenes (Fig. 1). In the bulk of the liquid phase, however, the interaction with the surrounding charged particles stabilizes the ionic form. 8 Nevertheless, the carbene could be trapped by palladium(II) acetate from imidazoliumbased ILs 2c-d including the acetate, 9a or by elemental chalcogens 9a from 1-ethyl-3-methylimidazolium acetate (EMIM-Ac) forming imidazole-2-chalcogenones. 9a Surprisingly, EMIM-Ac in a 1 : 1
Monatshefte f�r Chemie / Chemical Monthly, 2004
Journal of Molecular Catalysis B: Enzymatic, 2013
The effect of temperature on enantiomeric ratio (E) and specific reaction rate (r flow) in the co... more The effect of temperature on enantiomeric ratio (E) and specific reaction rate (r flow) in the continuousflow mode acetylation of (±)-1-phenylethanamine (rac-1a), (±)-4-phenylbutan-2-amine (rac-1b) and (±)-1,2,3,4-tetrahydro-1-naphthalenamine (rac-1c) by variously immobilized Candida antarctica lipase B biocatalysts was studied in the 0-70 • C range. In the continuous-flow kinetic resolutions with differently immobilized CaLB biocatalysts, the character of temperature effect depended significantly both on the substrate and on the mode of immobilization. Alteration of E in the kinetic resolutions of three differently flexible amines rac-1a-c as a function of temperature was rationalized by the various flexibility of the lipase in its different forms. Our results indicated that the optimal method of immobilization depended both on the nature of the substrate and the reaction conditions.
European Journal of Organic Chemistry, 1999
ABSTRACT
Composites Part A: Applied Science and Manufacturing, 1998
Interfacial interactions significantly influence the properties of particulate filled polymers. T... more Interfacial interactions significantly influence the properties of particulate filled polymers. The adhesion between the particles and the polymer matrix depends on the size (area) of the interface and the strength of the interaction. While the former quantity is related to the specific surface area of the filler, the strength of the interaction can be modified by its surface treatment. In the current experiments polypropylene composites were prepared which contained different amounts of filler treated with eight functional trialkoxy silane coupling agents and the routinely used stearic acid, for comparison. Tensile properties of the composites were determined and the effect of interfacial interaction was evaluated by semi-empirical equations developed previously. Significant difference was detected in the effect of the various silane coupling agents. Amino functional silanes increase the strength of the interaction considerably. The other coupling agents reduce the surface tension of the filler, which leads to a decrease in the reversible work of adhesion between the filler and the polymer. These changes result in a decrease in the tensile strength of the composite. The results also prove the validity of the model equations applied. Parameter B, a measure of the strength of the interaction, was calculated for each silane coupling agent thus quantitatively characterizing their effectiveness.