TY - JOUR AU - Pálovics, Emese Csilla AU - Bánhegyi, Dorottya Fruzsina AU - Pataki, Hajnalka AU - Szilágyi, Botond TI - Enhancing temperature cycle-induced deracemization via combined cooling and antisolvent crystallization: A proof of concept study JF - ARABIAN JOURNAL OF CHEMISTRY J2 - ARAB J CHEM VL - 17 PY - 2024 IS - 1 SN - 1878-5352 DO - 10.1016/j.arabjc.2023.105362 UR - https://m2.mtmt.hu/api/publication/34342442 ID - 34342442 N1 - Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, Budapest, H-1111, Hungary Department of Chemical and Environmental Process Engineering, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, Budapest, H-1111, Hungary Export Date: 16 November 2023 Correspondence Address: Szilágyi, B.; Department of Chemical and Environmental Process Engineering, Műegyetem rkp. 3, Hungary; email: szilagyi.botond@vbk.bme.hu AB - This study investigates the enhancement possibilities of the temperature cycle-induced deracemization (TCID) process by solubility adjustments through solvent system compositions. The research hypothesizes that combined cooling and antisolvent crystallization (CCAS) can accelerate the deracemization through two effect. Firstly, the higher solubility at the beginning of the process ensures that the concentrations are raised, which translates to higher racemization reaction productivity. Secondly, well-chosen antisolvent dosing can reduce the solubility (hence, increase the solid loading) in line with the progression of deracemization. This means that the solid phase's enantiomeric excess (EE) remains relatively high throughout the process, a condition known to accel-erate deracemization. The concept is tested in TCID experiments at different solvent system compositions, indicating that higher solubility increases the apparent deracemization rate, partly at the expense of yield. The CCAS experiment revealed that the yield and the product's EE could be improved simultaneously. The case study analyzed the glutamic acid (Glu) deracemization in the presence of the salicylaldehyde catalyst, using water as the solvent and acetic acid (AA) as the antisolvent. Comprehensive solubility measurements that enabled the design of experiments are also a part of this study. LA - English DB - MTMT ER - TY - JOUR AU - Bánhegyi, Dorottya Fruzsina AU - Madarász, János AU - Fogassy, Elemér AU - Pálovics, Emese Csilla AU - Pokol, György TI - Crystalline Forms of 4,4'-Methylenediantipyrine: Crystallographic Unit Cell for the Anhydrous Form, from Laboratory Powder XRD Pattern by DASH Program Package JF - PERIODICA POLYTECHNICA-CHEMICAL ENGINEERING J2 - PERIOD POLYTECH CHEM ENG VL - 67 PY - 2023 IS - 4 SP - 557 EP - 564 PG - 8 SN - 0324-5853 DO - 10.3311/PPch.22950 UR - https://m2.mtmt.hu/api/publication/34204776 ID - 34204776 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office-NKFIH through OTKA [124180, FK138475, 146218] Funding text: E.F. and E.P. are grateful for the past and future support of the National Research, Development and Innovation Office-NKFIH through OTKA grant Nos. 124180 and FK138475 and 146218, respectively. The authors are also grateful to Mr. David Susko for his substantial help in the preparative work. AB - Crystalline unit cell structure of anhydrous title compound, diantipyrinylmethane (CAS Registry No. 1251-85-0), a substance usually obtained as a by-product in Mannich type reactions of antipyrine, has been modelled by the help of powder X-ray diffraction, applying the DASH software package and crystal coordinates coming from former single crystal X-ray structure determinations (CSD codes FADDIY and FADDIY01) of its monohydrate. The unit cell of the anhydrate compound belongs to the monoclinic space group P21/a, with unit cell parameters of a = 14.604, b = 9.858, c = 14.509 Å, β = 95.56 °, V = 2078.9 Å3, Z = 4, Z ' = 1. Comparisons of FT-IR spectrum and thermal behavior of the anhydrous and monohydrated forms confirm differences in degree of hydration and solid state structure, while those of 1H- and 13C NMR-spectra show their molecular identity. LA - English DB - MTMT ER - TY - JOUR AU - Pálovics, Emese Csilla AU - Madarász, János AU - Pokol, György AU - Fogassy, Elemér AU - Bánhegyi, Dorottya Fruzsina TI - Economic Separations of Organic Acidic or Basic Enantiomeric Mixtures—A Protocol Suggestion JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 1 PG - 23 SN - 1661-6596 DO - 10.3390/ijms24010846 UR - https://m2.mtmt.hu/api/publication/33543852 ID - 33543852 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office-NKFIH [FK138475] Funding text: This research was funded by the National Research, Development and Innovation Office-NKFIH, Grant/Award Number: FK138475. AB - In this review, we aim to present new concepts for the revisited separation of enantiomers from racemic compounds and a protocol worth to be followed in designing the preparation of pure enantiomers. We have taken into account not only the influence of the properties (eutectic composition) and characteristics of the reactants (racemic compound, resolving agent), but also the behavior of the resulting diastereomers and the different conditions (e.g., crystallization time, solvents used, solvate-forming compounds, achiral additives, etc.). The examples discussed are resolutions developed by our research team, through which we will try to illustrate the impact of all these considerations, presenting the methodological investigations interpreting recent discoveries and observations. Some special solid-state analytical and structural investigations assisting us in the elucidation and invention design of the resolution processes of some active pharmaceutical ingredients, such as Tetramisole, tofisopam, and Amlodipine, are also shown. LA - English DB - MTMT ER - TY - CHAP AU - Pálovics, Emese Csilla AU - Bánhegyi, Dorottya Fruzsina ED - Reedijk, J. TI - The Behavior of Not Only Structurally Similar Molecules in the Resolution Processes T2 - Reference Module in Chemistry, Molecular Sciences and Chemical Engineering PB - Elsevier CY - Waltham (MA) SN - 9780124095472 PY - 2022 PG - 8 DO - 10.1016/B978-0-32-390644-9.00009-3 UR - https://m2.mtmt.hu/api/publication/33758572 ID - 33758572 LA - English DB - MTMT ER - TY - JOUR AU - Bánhegyi, Dorottya Fruzsina AU - Fogassy, Elemér AU - Madarász, János AU - Pálovics, Emese Csilla TI - Optical Resolution of Two Pharmaceutical Bases with Various Uses of Tartaric Acid Derivatives and Their Sodium Salts: Racemic Ephedrine and Chloramphenicol Base JF - MOLECULES J2 - MOLECULES VL - 27 PY - 2022 IS - 10 SN - 1420-3049 DO - 10.3390/molecules27103134 UR - https://m2.mtmt.hu/api/publication/32827003 ID - 32827003 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office-NKFIH through OTKA [124180] Funding text: This work was supported by the National Research, Development and Innovation Office-NKFIH through OTKA grant 124180. LA - English DB - MTMT ER - TY - JOUR AU - Bánhegyi, Dorottya Fruzsina AU - Szolcsányi, D. AU - Madarász, János AU - Pálovics, Emese Csilla TI - Enantiomeric separation of racemic amlodipine by sequential fractional crystallization through formation of diastereomeric salt solvates and co-crystals of solvate-like compounds with specific structure — A tandem resolution JF - CHIRALITY: THE PHARMACOLOGICAL BIOLOGICAL AND CHEMICAL CONSEQUENCES OF MOLECULAR ASYMMETRY J2 - CHIRALITY VL - 34 PY - 2022 IS - 2 SP - 374 EP - 395 PG - 22 SN - 0899-0042 DO - 10.1002/chir.23373 UR - https://m2.mtmt.hu/api/publication/32518549 ID - 32518549 N1 - Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budapest, Hungary Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Budapest, Hungary Export Date: 1 December 2021 CODEN: CHRLE Correspondence Address: Pálovics, E.; Department of Organic Chemistry and Technology, Hungary; email: palovics.emese@vbk.bme.hu AB - A new resolution method of racemic amlodipine has been developed. The racemic compound is reacted in a suitable solvent with 0.25-mol equivalent of (R,R)-tartaric acid. After the decomposition of the diastereomeric salt, the remaining racemic fraction is precipitated with half-equivalent of fumaric acid, and the pure amlodipine enantiomer is obtained. A quarter equivalent of the same resolving agent, (R,R)-tartaric acid has been also added to the mother liquor to obtain the other enantiomer. The advantage of this method is that both of the enantiomers of amlodipine could be obtained with high enantiomeric excess with the same resolving agent. The racemic excess can also be isolated and re-resolved. Achiral reagents (urea and thiourea) have been added to the resolving agent. These neutral additives are incorporated as co-crystals in the structure of the diastereomeric salts. The used solvate-former solvents and achiral additives are structurally similar, and their presence can enable the fractional separation of the diastereomers. In addition, the racemate, the enantiomers, and some intermediate salts with high diastereomeric excess obtained in the resolution process of amlodipine have been also subjected to thermal (DSC, TG/DTA-EGA-MS, and -FTIR), analytical (FTIR spectroscopic), and structural (XRD) comparisons, which indicate that the key-intermediate crystalline diastereomeric salts—as solvates and co-crystals—inherit a kind of structural similarity from their related additives—solvents (DMF, DMAA, and DMSO) or (thio)ureas, respectively. LA - English DB - MTMT ER - TY - CHAP AU - Bánhegyi, Dorottya Fruzsina AU - Pálovics, Emese Csilla ED - Bodor, Zsanett TI - Miért és hogyan befolyásolja az enantiomerkeverékek viselkedése a belőlük keletkező diasztereomer sók elválasztásának eredményét? T2 - II. FKF Szimpózium Konferencia Kiadvány PB - Magyar Kémikusok Egyesülete (MKE) CY - Budapest SN - 9786156018052 PY - 2021 SP - 10 EP - 14 PG - 5 UR - https://m2.mtmt.hu/api/publication/32679229 ID - 32679229 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Bánhegyi, Dorottya Fruzsina AU - Pálovics, Emese Csilla TI - The Stoichiometry, Structure and Possible Formation of Crystalline Diastereomeric Salts JF - SYMMETRY (BASEL) J2 - SYMMETRY-BASEL VL - 13 PY - 2021 IS - 4 PG - 12 SN - 2073-8994 DO - 10.3390/sym13040667 UR - https://m2.mtmt.hu/api/publication/32354474 ID - 32354474 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office-NKFIH through OTKAOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [124180] Funding text: The authors thank Emeritus Elemer Fogassy for his valuable and constructive suggestions during the planning and development of this research work. His willingness to give his time so generously has been very much appreciated. This work was supported by the National Research, Development and Innovation Office-NKFIH through OTKA grants 124180. AB - Knowing the eutectic composition of the binary melting point phase diagrams of the diastereomeric salts formed during the given resolution, the achievable F (F = ee(Dia)*Y) value can be calculated. The same value can also be calculated and predicted by knowing the eutectic compositions of the binary melting point phase diagrams of enantiomeric mixtures of the racemic compound or the resolving agent. An explanation was sought as to why and how the crystalline precipitated diastereomeric salt-formed in the solution between a racemic compound and the corresponding resolving agent-may be formed. According to our idea, the self-disproportionation of enantiomers (SDE) has a decisive role when the enantiomers form two nonequal ratios of conformers in solution. The self-organized enantiomers form supramolecular associations having M and P helicity, and double helices are formed. Between these double spirals, with the formation of new double spirals, a dynamic equilibrium is achieved and the salt crystallizes. During this process between acids and bases, chelate structures may also be formed. Acids appear to have a crucial impact on these structures. It is assumed that the behavior of each chiral molecule is determined by its own code. This code validates the combined effect of constituent atoms, bonds, spatial structure, charge distribution, flexibility and complementarity. LA - English DB - MTMT ER - TY - JOUR AU - Bánhegyi, Dorottya Fruzsina AU - Fogassy, Elemér AU - Pálovics, Emese Csilla TI - Possibilities of Exploiting Kinetic Control in the Continuous Fractional Crystallization of Diastereomeric Mixtures JF - SYMMETRY (BASEL) J2 - SYMMETRY-BASEL VL - 13 PY - 2021 IS - 8 SP - 1516 SN - 2073-8994 DO - 10.3390/sym13081516 UR - https://m2.mtmt.hu/api/publication/32171249 ID - 32171249 N1 - Export Date: 16 February 2022 Correspondence Address: Pálovics, E.; Department of Organic Chemistry and Technology, Hungary; email: palovics.emese@vbk.bme.hu LA - English DB - MTMT ER - TY - JOUR AU - Bánhegyi, Dorottya Fruzsina AU - Pálovics, Emese Csilla TI - Investigation of the behaviour of pregabalin enantiomers JF - Chemical & Pharmaceutical Research J2 - Chem Pharm Res VL - 2 PY - 2020 IS - 1 SP - 1 EP - 5 PG - 5 SN - 2689-1050 DO - 10.33425/2689-1050.1015 UR - https://m2.mtmt.hu/api/publication/31650096 ID - 31650096 LA - English DB - MTMT ER -