421Acta Chim. Slov. 2020, 67, 421–434 Milićević et al.: Preparation of Quinoline-2,4-dione Functionalized ... DOI: 10.17344/acsi.2019.5375 Scientific paper Preparation of Quinoline-2,4-dione Functionalized 1,2,3-Triazol-4-ylmethanols, 1,2,3-Triazole-4-carbaldehydes and 1,2,3-Triazole-4-carboxylic Acids David Milićević,1 Roman Kimmel,1 Damijana Urankar,2 Andrej Pevec,2 Janez Košmrlj2,* and Stanislav Kafka1,* 1 Faculty of Technology, Tomas Bata University in Zlin, Vavrečkova 275, 760 01 Zlin, Czech Republic 2 Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia * Corresponding author: E-mail: kafka@utb.cz; Janez.Kosmrlj@fkkt.uni-lj.si Tel: (+420)-576031115, (+386)-14798558 Received: 06-30-2019 Dedicated to Professor František Liška, University of Chemistry and Technology, Prague and Charles University, on the occasion of his 80th birthday. Abstract (1-(2,4-Dioxo-1,2,3,4-tetrahydroquinolin-3-yl)-1H-1,2,3-triazol-4-yl)methyl acetates substituted on nitrogen atom of quinolinedione moiety with propargyl group or (1-substituted 1H-1,2,3-triazol-4-yl)methyl group, which are availa- ble from the appropriate 3-(4-hydroxymethyl-1H-1,2,3-triazol-1-yl)quinoline-2,4(1H,3H)-diones unsubstituted on quinolone nitrogen atom by the previously described procedures, were deacetylated by acidic ethanolysis. Thus obtained primary alcohols, as well as those aforenamed unsubstituted on quinolone nitrogen atom, were oxidized to aldehydes on the one hand with pyridinium chlorochromate (PCC), on the other hand with manganese dioxide, and to carboxylic acids using Jones reagent in acetone. The structures of all prepared compounds were confirmed by 1H, 13C and 15N NMR spectroscopy. The corresponding resonances were assigned on the basis of the standard 1D and gradient selected 2D NMR experiments (1H–1H gs-COSY, 1H–13C gs-HSQC, 1H–13C gs-HMBC) with 1H–15N gs-HMBC as a practical tool to determine 15N NMR chemical shifts at the natural abundance level of 15N isotope. Keywords: 1,2,3-triazole; quinoline-2,4-dione; hydroxymethylderivatives; aldehydes; carboxylic acids 1. Introduction 1,4-Disubstituted 1,2,3-triazole is considered to be a suitable structural part of compounds that could be of inter- est from the point of view of various research areas. Apart from many applicable properties including coordination1–3 and catalytic abilities,4 as well as photophysical and electro- chemical characteristics,5–8 1,2,3-triazoles further exhibit large variety of medical activities.9–14 Some of us have previ- ously dealt with preparation of pyridine appended 1,2,3-tri- azoles and their synthetic utilization.15 1,2,3-Triazolium salts prepared from them have shown an efficiency in palla- dium-catalyzed Suzuki–Miyaura coupling.15 From these salts, Ru(II) complexes were prepared, which have shown a catalytic activity in the oxidation of alcohols with tert-butyl hydroperoxide.16 Cp*-Ir(III) complexes with additional chelating ligands containing 1,2,3-triazole ring are useful as catalysts for oxidation of cyclooctane to cyclooctanone.17 A bis(pyridyl-functionalized 1,2,3-triazol-5-ylidene)-palladi- um(II) complex [Pd(Py-tzNHC)2]2+ was found to catalyze the copper-, amine-, phosphine-, and additive-free aerobic Sonogashira alkynylation of (hetero)aryl bromides in water as the only reaction solvent.18 Similarly, quinoline-2,4-dione based compounds were also recognized as distinctively attractive species, when taking into account their versatile beneficial pur- posefulness.19 The mentioned fact inspired us to synthesize never before described 1,2,3-triazole- and quinoline-2,4(1H,3H) dione-based bis-heterocycles. In 2011, we reported the synthesis of 3-alkyl/aryl-3-(1H-1,2,3-triazol-1-yl)quino- line-2,4(1H,3H)-diones by the click reaction of appropri- 422 Acta Chim. Slov. 2020, 67, 421–434 Milićević et al.: Preparation of Quinoline-2,4-dione Functionalized ... ate 3-azidoquinolinediones with terminal alkynes.20 In the same year, the patent application21 was administered, which comprised preparation of tautomeric 4-hydroxy- quinolin-2-ones with 1,2,3-triazol-1-yl group in position 3 of quinolinone scaffold that are effective as adenosine mo- nophosphate-activated protein kinase (AMPK) activators. Since then still more reports on the 4-hydroxy-quino- lin-2-one derivatives, in which hydrogen atom of hydroxyl group was replaced with various substituents comprising 1,2,3-triazole pattern, have been published.22–29 Some of these substances have been found to show some acetylcho- line receptors binding affinity.22 Recently we have reported an utilization of the above mentioned 3-(1H-1,2,3-triazol- 1-yl)quinoline-2,4(1H,3H)-diones unsubstituted on the nitrogen atom of the quinolone moiety for the synthesis of bis(1,2,3-triazole) functionalized quinoline-2,4-diones.30 In frame of that study,30 in place of starting materials were used, among others, derivatives of (1H-1,2,3-triazol-4-yl) methanol, in which hydroxyl group was protected by acetylation and their structure was subsequently modified. There was offered the idea of the removal of protecting acetyl group and the oxidative conversion of thus obtained primary alcohols as well as starting triazolylmethanols to the corresponding 1,2,3-triazole-4-carbaldehydes and 1,2,3-triazole-4-carboxylic acids. In terms of biological effects, 1,2,3-triazole-4-carbal- dehydes are particularly interesting. For example, a series of them has been found to prove tuberculostatic effect.31 Some (1H-1,2,3-triazol-4-yl)methanols exhibit cytotoxic activity.32 Some known 1-substituted 1,2,3-triazol-4-car- boxylic acids have antibacterial effect against Staphylococ- cus aureus.33 2. Results and Discussion Compounds 1, 2 and 3 (Figure 1) were obtained through the multistep synthetic pathway, which we have developed recently,30 and were utilized as starting com- pounds in this study. Although acetates 1a,b were prepared by acetylation of the corresponding primary alcohols 4a,b,30 we exploit- ed them as model compounds and dealt with finding a suitable procedure for their deacetylation back to the men- tioned alcohols so that we can apply it to prepare alcohols 5a,b and 6a–f from the more laboriously obtainable corre- sponding acetates 2a,b and 3a–f. At first, we tried process- ing with a methanolic solution of sodium methoxide, how- ever, in parallel with ester methanolysis, undesirable nucleophilic quinoline-2,4-dione ring opening and suc- cessive reactions took place resulting in mixtures, from which only corresponding N-substituted anthranilic acids and eventually their methyl esters were isolated after neu- tralization with diluted hydrochloric acid. Also alkaline hydrolysis of ester group is accompanied with above men- tioned ring opening; the treatment of 1b with a solution of potassium hydroxide in aqueous ethanol afforded corre- sponding anthranilic acid as main product. Finally, acidic alcoholysis (37% HCl : EtOH 1:100 v/v) has proved to be suitable. After the successful deacetyl- Figure 1. Subject compounds Table 1. Acidic alcoholysis of acetates 1a,b, 2a,b, and 3a–f. Entry Acetate R1 R2 Time (h) Alcohol Yield (%) 1 1a Me – 3 4a 92a 2 1b Ph – 3 4b 93a 3 2a Me – 3 5a 83b 4 2b Ph – 3 5b 87b 5 3a Me Bn 3.5 6a 86a 6 3b Me Ph 3.5 6b 98a 7 3c Me 2-Py 2.5 6c 80a 8 3d Ph Bn 4 6d 89a 9 3e Ph Ph 3 6e 97a 10 3f Ph 2-Py 3 6f 87a a Refers to pure (by TLC and IR) isolated product. b Refers to per- cent yield of crystallized product. 423Acta Chim. Slov. 2020, 67, 421–434 Milićević et al.: Preparation of Quinoline-2,4-dione Functionalized ... ation of compounds 1a,b, this method was applied also to deacetylation the acetates 2a,b and 3a–f. This reaction was carried out by boiling the reaction mixtures and was fin- ished in 2.5–4 hours. The appropriate primary alcohols were obtained with yields 80–90% (see Table 1). The reaction conditions of the conversion of pre- pared alcohols to the corresponding aldehydes were opti- mized for the oxidation of alcohols 4a,b to aldehydes 7a,b. The results are summarized in the Table 2. From the range of usual reagents used for these transformations, we first chose pyridinium chlorochromate (PCC). As can be found in literature,34 oxidations of primary alcohol to aldehydes can proceed smoothly with good yields using 1.2 mmol PCC per 1 mmol substrate in dichloromethane (DCM) at room temperature. However, the conversion of 4a under these conditions is very slow, because of its low solubility in DCM. Boiling the reaction mixture, and particularly by performing the reaction in a microwave reactor in a closed vial at 40 °C, the time required to react the substrate is sig- nificantly reduced, but at the same time decreases the yield of 7a. Higher yields of 7a were achieved when DCM was replaced with acetone, in which 4a is more soluble; we have achieved the best yield (36%) of 7a by increasing the excess of PCC and allowing the reaction to proceed for 22 hours at room temperature. Oxidation of 4b, which is more soluble in DCM than its methyl analogue 4a, was performed in this solvent with the best yield (44%) of 7b using 1.2 mmol PCC per 1 mmol 4b and boiling of the reaction mixture, whereas the reac- tion was finished within 1.5 hour. When the mixture of the same initial composition was heated in a microwave reac- tor in a closed vial to 40 °C for 10 minutes, the yield of 7b was only slightly lower than the former. The same applies to carrying out the reaction in DCM with 1.5 mmol PCC per 1 mmol 4b at room temperature. Further increasing of the amount of PCC results in a shorter reaction time to- gether with a reduction of yield of 7b. In contrast to oxida- tion of 4a to 7a, the oxidation of 4b with PCC in acetone under the same conditions furnished the aldehyde 7b with significantly lower yield. Apart from oxidation with PCC, Swern reaction, i.e. oxidation with dimethylsulfoxide (DMSO) in the pres- ence of oxalyl chloride and N,N-diisopropylethylamine (DIPEA), was also briefly examined using slightly modi- fied synthetic procedure from the literature,35 however obtained yields were unsatisfactory for both, phenyl and methyl mono-triazole derivatives 7a and 7b, respectively. While the former resulted in 33% yield of isolated prod- uct, no product was isolated in case of the latter. The main drawback of this approach is presence of hardly remov- able dimethyl sulfoxide that remained in our products despite the fact that they were several times washed with ice-cold water. Apparently, utilization of relatively large quantities of water also caused significant loses of target compounds that were much more obvious in the case of methyl derivative 7a. Moreover, we have experience that our 1,2,3-triazole- and quinoline-2,4-dione-based bis-heterocycles are more or less unstable in DMSO and therefore, the use of this solvent in their preparation is not always appropriate. As the third option, oxidation of primary alcohols 4a,b with MnO2 was further studied. Comparing the reac- tion parameters such as reaction times and quantities of reagents, acetone was recognized superior in comparison Table 2. Oxidation of primary alcohols 4a,b to aldehydes 7a,b.a Entry Alcohol R1 Reagent n (mmol)b Time (h) Solvent Aldehyde Yield (%) 1 4a Me PCC 1.7 22c Me2CO 7a 36d 2 4a Me PCC 1.2 22c CH2Cl2 7a 31d 3 4a Me PCC 1.2 0.17e CH2Cl2 7a 16 4 4a Me PCC 1.2 1.5 CH2Cl2 7a 15 5 4a Me PCC 1.2 5 Me2CO 7a 23d 6 4b Ph PCC 1.7 1.5c CH2Cl2 7b 35 7 4b Ph PCC 1.7 22c Me2CO 7b 26d 8 4b Ph PCC 1.7 0.5 CH2Cl2 7b 34 9 4b Ph PCC 2.0 1c CH2Cl2 7b 31 10 4b Ph PCC 1.5 4c CH2Cl2 7b 41 11 4b Ph PCC 1.2 1.5 CH2Cl2 7b 44 12 4b Ph PCC 1.2 0.17e CH2Cl2 7b 42 13 4a Me DMSO 2.6 3.5f Me2CO 7a 0 14 4b Ph DMSO 2.6 3.5f CH2Cl2 7b 33 15 4a Me MnO2 10 1.25 Me2CO 7a 60 16 4b Ph MnO2 10 1.5 Me2CO 7b 58 17 4b Ph MnO2 15g 3 CH2Cl2 7b 62 18 4b Ph MnO2 10 96c CH2Cl2 7b 44 a Reactions were carried out in boiling reaction mixtures unless indicated otherwise. b Amount of reagent per 1 mmol of alcohol. c Carried out at room temperature. d Complete consumption of 4 was not reached. e Carried out in the microwave reactor at 40 °C. f For the reaction conditions see Experimental. g Reaction was started with 10 mmol of MnO2, additional 5 mmol of MnO2 were added after 2 hours. 424 Acta Chim. Slov. 2020, 67, 421–434 Milićević et al.: Preparation of Quinoline-2,4-dione Functionalized ... with dichloromethane, while transformation yields were practically the same (approx. 60%) in both cases. The findings from the above experiments were used in the oxidation of primary alcohols 5a,b and 6a–f to alde- hydes 8a,b and 9a–f, respectively. In all cases, oxidation was carried out using PCC under optimum conditions for the conversion of alcohol 4b to aldehyde 7b, i.e. using 1.2 mmol PCC per 1 mmol alcohol in dichloromethane at the reflux temperature. Furthermore, the aldehydes 8a,b and 9b were prepared from the corresponding alcohols by oxi- dation with MnO2 in acetone. Due to the very similar yields of aldehydes achieved with the use of one or the oth- er reagent and the toxicity of CrVI-containing reagents, it can be stated that MnO2 is a more advantageous agent than PCC. So far described oxidations of triazolyl-4-methanols to the corresponding carboxylic acids were carried out mostly with permanganate in basic medium.36–38 In one case, the oxidation with a mixture of sodium chlorite and sodium hypochlorite with an addition of 2,2,6,6-te- tramethylpiperidine N-oxide (TEMPO) in phosphate buf- fer was patented.39 Since basic media causes destruction of quinolinedione scaffold, the choice of reagents for the oxi- dation of alcohols 4a,b, 5a,b, and 6a–f is limited to those, for which the presence of no base is needed. For the trans- formation of these alcohols to carboxylic acids 10a,b, 11a,b, and 12a–f, we decided to try out Jones reagent (solution of CrO3 in diluted sulfuric acid) in acetone. While this method has long been known and its use for the preparation of carboxylic acids has been described in many cases, we have found in the literature only one re- port40 on its use for the preparation of triazole-4-carboxyl- ic acids, which were intermediates in a multistep synthesis, without giving their yields and experimental details. Al- though at most 9 mol of CrO3 per one mol of primary al- cohol is usually used,41–43 in the cases provided herein, it has been shown that the most suitable ratio is 24 mol CrO3 per 1 mol of primary alcohol (Table 4). The acid with methyl group in position 3 of quinolone scaffold 10a was isolated in a considerably lower yield than its phenyl ana- logue 10b probably due to its significantly higher solubility in water. All compounds were characterized by 1H and 13C and, in cases of 6a–e, 7a,b, 9a–f, 10a, and 12a–f, also by 15N NMR spectroscopy. The corresponding resonances Table 4. Oxidation of primary alcohols 4a,b, 5a,b, and 6a–f to car- boxylic acids 10a,b, 11a,b, and 12a–f, respectivelya. Entry Alcohol R1 R2 Time (h) Carboxylic Yield (%) acid 1 4a Me – 2.75 10a 33 2 4b Ph – 3 10b 40b 3 4b Ph – 3.25 10b 71 4 5a Me – 2.5 11a 55 5 5b Ph – 3 11b 68 6 6a Me Bn 3 12a 88 7 6b Me Ph 2.5 12b 92 8 6c Me 2-Py 2.5 12c 84 9 6d Ph Bn 2 12d 75 10 6e Ph Ph 2.25 12e 77 11 6f Ph 2-Py 2.5 12f 69 a  CrO3 (2.4 g, 24mmol) in 2m H2SO4 (24 mL) per 1 mmol of alcohol was used, unless otherwise stated. b  CrO3 (600 mg, 6.0 mmol) in 2m H2SO4 (6 mL) per 1 mmol of alcohol 4b was used, complete consumption of an intermediate (apparently aldehyde 7b) was not reached according to TLC. Table 3. Oxidation of primary alcohols 5a,b and 6a–f to aldehydes 8a,b and 9a–f, respectively. Entry Alcohol R1 R2 Reagent Time (h) Solvent Aldehyde Yield (%) 1 5a Me – PCC 1 CH2Cl2 8a 41 2 5a Me – MnO2 1.25 Me2CO 8a 40 3 5b Ph – PCC 0.75 CH2Cl2 8b 38 4 5b Ph – MnO2 2 Me2CO 8b 38 5 6a Me Bn PCC 0.5 CH2Cl2 9a 41 6 6b Me Ph PCC 0.5 CH2Cl2 9b 40 7 6b Me Ph MnO2 0.75 Me2CO 9b 51 8 6c Me 2-Py PCC 0.75 CH2Cl2 9c 48 9 6d Ph Bn PCC 0.5 CH2Cl2 9d 41 10 6e Ph Ph PCC 0.5 CH2Cl2 9e 45 11 6f Ph 2-Py PCC 0.5 CH2Cl2 9f 41 Figure 2. Designation of positions in the structure of prepared com- pounds. 425Acta Chim. Slov. 2020, 67, 421–434 Milićević et al.: Preparation of Quinoline-2,4-dione Functionalized ... were assigned on the basis of gradient-selected 2D NMR experiments including 1H–1H gs-COSY, 1H–13C gs- HSQC, 1H–13C gs-HMBC and 1H–15N gs-HMBC. Atoms and rings labeling scheme, which was extensively applied in the »Experimental« section is presented in Figure 2. From the solution of 12d in deuteriochloroform originally designed to measure NMR spectra, the crystal has grown, which we have used to corroborate the struc- ture of this compound (Figure 3) by the single crystal X-ray structure determination. It has been found that the crystal is a solvate 12d · 2CDCl3. Selected bond lengths and angles are displayed in Table 5. The X-ray diffraction study has shown that the solvate 12d · 2CDCl3 crystallizes in monoclinic P21/n space group. Intermolecular hydro- gen bonds of the type O–H···N are found in the crystal structure of compound 12d · 2CDCl3. Atom O2 acts as hy- drogen bond donor and N5 of symmetry related molecule as acceptor and thus forming two dimensional chain ex- tending along the b-axis (Figure 4, Table 6). Figure 3. Crystallographic view and numbering scheme of the mol- ecule 12d · 2CDCl3. CDCl3 molecules are omitted for clarity. Figure 4. Hydrogen bonding interactions in the crystal structure of 12d·2CDCl3 showing the polymeric chain. Symmetry code: (i) x, y+1, z. Table 5. Selected bond lengths (Å) and angles (°) for compound 12d · 2CDCl3. N1–N2 1.298(5) N1–N2–N3 106.8(3) N2–N3 1.359(5) N5–N6–N7 106.8(4) N5–N6 1.310(5) N2–N3–C3 110.7(3) N6–N7 1.328(6) N6–N7–C21 111.2(4) N1–C2 1.353(5) N1–C2–C3 108.3(4) N3–C3 1.330(5) N3–C3–C2 104.9(3) N3–C4 1.456(5) N4–C17–C12 119.9(4) N4–C17 1.424(5) N4–C18–C4 118.0(3) N4–C18 1.358(5) N4–C19–C20 112.1(3) N4–C19 1.475(5) N5–C20–C21 107.0(4) N5–C20 1.348(6) N7–C21–C20 105.4(4) N7–C21 1.328(6) C17–N4–C18 123.2(3) N7–C22 1.481(6) C19–N4–C17 121.9(4) Table 6. Hydrogen bonding geometry for compound 12d · 2CDCl3. D–H…A D–H (Å) H…A (Å) D…A (Å) D–H…A (°) Symmetry code O2–H2…N5 0.82 1.90 2.700(5) 166.7 x, y+1, z 3. Conclusions A collection of novel 1,2,3-triazole- and quino- line-2,4(1H,3H)-dione based bis-heterocycles functional derivatives was prepared and characterized by IR, NMR and HRMS. Appropriate starting compounds with 4-(ace- toxymethyl)-1H-1,2,3-triazole moiety were firstly deacetylated, and the obtained corresponding alcohols were further oxidized to aldehydes and carboxylic acids. Investigation of transformation approaches was carried 426 Acta Chim. Slov. 2020, 67, 421–434 Milićević et al.: Preparation of Quinoline-2,4-dione Functionalized ... out using more accessible mono-triazoles, while optimized reaction conditions were then utilized for preparation of bis-triazole counterparts in moderate to excellent yields. Synthesized derivatives could potentially possess some de- sirable properties or might be exploited as precursors in further transformations. In this article we present a group of new quino- line-2,4-dione based compounds with primary alcohol, aldehyde or carboxyl functional group on 1,2,3-triazole. Even though, the chemistry applied throughout the syn- theses of our final materials is pretty elemental and straightforward, we believe that we have been handling with very promising substances and therefore, in our opin- ion, it was worthwhile to deal with them. Prepared com- pounds would not only potentially exhibit some extraordi- nary characteristics, but may also serve as precursors in further reactions such as esterification, peptide bond for- mation, nucleophilic additions to formyl group etc. 4. Experimental The reagents and solvents were used as obtained from the commercial sources. Column chromatography was carried out on Fluka Silica gel 60 (particle size 0.063– 0.2 mm, activity acc. Brockmann and Schodder 2–3). Melting points were determined on the microscope hot stage, Kofler, PolyTherm, manufacturer Helmut Hund GmbH, Wetzlar and are uncorrected. TLC was carried out on pre-coated TLC sheets ALUGRAM® SIL G/UV254 for TLC, MACHEREY-NAGEL. NMR spectra were recorded with a Bruker Avance III 500 MHz NMR instrument oper- ating at 500 MHz (1H), 126 MHz (13C) and 51 MHz (15N) at 300 K, or JEOL ECZ400R/S3 instrument operating at 400 MHz (1H) and 100 MHz (13C). Proton spectra were referenced to TMS as internal standard, in some cases to the residual signal of DMSO-d5 (at δ 2.50 ppm) or CHCl3 (at δ 7.26 ppm). Carbon chemical shifts were determined relative to the 13C signal of DMSO-d6 (39.52 ppm) or CDCl3 (77.16 ppm). 15N chemical shifts were extracted from 1H–15N gs-HMBC spectra (with 20 Hz digital resolu- tion in the indirect dimension and the parameters adjust- ed for a long-range 1H–15N coupling constant of 5 Hz) determined with respect to external nitromethane and are corrected to external ammonia by addition of 380.5 ppm. Nitrogen chemical shifts are reported to one decimal place as measured of the spectrum, however, the data should not be considered to be more accurate than ±0.5 ppm because of the digital resolution limits of the experiment. Chemical shifts are given on the δ scale (ppm). Coupling constants (J) are given in Hz. Multiplicities are indicated as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet) or br (broadened). Infrared spectra were recorded on FT- IR spectrometer Alpha (Bruker Optik GmbH Ettlingen, Germany) using samples in potassium bromide disks and only the strongest/structurally most important peaks are listed. HRMS spectra were recorded with Agilent 6224 Ac- curate Mass TOF LC/MS system with electrospray ioniza- tion (ESI). X-ray crystallography. The molecular structure of compound 12d was determined by single-crystal X-ray diffraction methods. Crystallographic data and refinement details are given in Table 7. Diffraction data for 12d were collected at room temperature with Agilent SuperNova dual source diffractometer using an Atlas detector and equipped with mirror-monochromated MoKα radiation (λ = 0.71073 Å). The data were processed by using CrysA- lis PRO.44 All the structures were solved using SHELXS-9745 and refined against F2 on all data by full-matrix least-squares with SHELXL–2016.46 All non-hydrogen atoms were refined anisotropically. The C3 and C21 bonded hydrogen atoms were located in a differ- ence map and refined with the distance restraints (DFIX) with C–H = 0.98 Å and with Uiso(H) = 1.2Ueq(C). All other hydrogen atoms were included in the model at geometri- cally calculated positions and refined using a riding model. The crystal structure 12d contains deuterated solvent mol- ecules (CDCl3). The D and H atoms are both treated as hydrogens but the SFAC instruction for D enables the for- mula weight and density to be calculated correctly. The C29 and C30 bonded deuterium atoms were located in a Table 7. Crystal data and structure refinement details for com- pound 12d · 2CDCl3. 12d · 2CDCl3 formula C30H21Cl6D2N7O4 Fw (g mol–1) 760.29 crystal size (mm) 0.50 × 0.30 × 0.10 crystal color colourless crystal system monoclinic space group P 21/n a (Å) 13.5462(6) b (Å) 11.9884(9) c (Å) 20.8335(10) β (º) 92.823(4) V (Å3) 3379.2(3) Z 4 calcd density (g cm–3) 1.494 F(000) 1544 no. of collected reflns 29191 no. of independent reflns 7754 Rint 0.0563 no. of reflns observed 3853 no. parameters 438 R[I> 2σ (I)]a 0.0974 wR2(all data)b 0.3413 Goof , Sc 1.092 maximum/minimum residual +0.90/–0.80 electron density (e Å–3) aR = ∑||Fo| – |Fc||/∑|Fo|. bwR2 = {∑[w(Fo2 – Fc2)2]/∑[w(Fo2)2]}1/2. cS = {∑[(Fo2 – Fc2)2]/(n/p}1/2 where n is the number of reflections and p is the total number of parameters refined. 427Acta Chim. Slov. 2020, 67, 421–434 Milićević et al.: Preparation of Quinoline-2,4-dione Functionalized ... difference map and refined with the distance restraints (DFIX) with C–D = 0.98 Å and with Uiso(D) = 1.2Ueq(C). CCDC 1892717 (for 12d · 2CDCl3) contain the sup- plementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crys- tallographic Data Centre via www.ccdc.cam.ac.uk/data_ request/cif. General procedure for the synthesis of alcohols 5a,b and 6a–f. A solution of appropriate acetate in acidified ethanol (37% HCl : EtOH 1:100 V/V) was stirred at the reflux tem- perature (90–100 °C in oil bath) for 2.5–4 hours. Obtained pale yellow solution was then allowed to cool to room tem- perature, and subsequently neutralized with saturated aqueous NaHCO3. Resulting suspension was concentrated by rotary evaporation in vacuo, diluted with deionized wa- ter and extracted with chloroform (3–6x 50 mL). Organic phases were joined together, washed with deionized water (1x50 mL), dried over anhydrous Na2SO4, filtered. and volatile components were evaporated in vacuo. The residu- al oily or solid product was then purified by chromatogra- phy on silica-gel column using 5% ethanol or 30% ethyl acetate in chloroform as eluent, or crystalized from ethyl acetate. 3-(4-(Hydroxymethyl)-1H-1,2,3-triazol-1-yl)-3-methyl- 1-(prop-2-ynyl)quinoline-2,4(1H,3H)-dione (5a). Color- less crystals, mp 182–188 °C (ethyl acetate); Rf = 0.12 (5% ethanol in chloroform); Rf = 0.31 (10% ethanol in chloro- form); 1H NMR (500 MHz, DMSO-d6) δ 2.08 (s, 3H), 3.35-3.38 (m, 1H), 4.56 (d, 2H, J = 5.7 Hz), 4.84 (dd, 1H, J = 18.1, 2.4 Hz), 4.95 (dd, 1H, J = 18.1, 2.4 Hz), 5.29 (t, 1H, J = 5.7 Hz), 7.36 (ddd, 1H, J = 7.6, 7.4, 0.9 Hz), 7.57 (d, 1H, J = 8.4 Hz), 7.89 (ddd, 1H, J = 8.4, 7.4, 1.7 Hz), 7.96 (dd, 1H, J = 7.8, 1.6  Hz), 8.26 (s, 1H); 13C NMR (126 MHz, DMSO-d6) δ 23.3, 32.6, 55.1, 72.4, 75.3, 78.3, 116.6, 119.2, 123.9, 124.1, 128.1, 137.1, 140.8, 147.5, 167.9, 189.8; IR (cm–1): ν 3270, 3134, 2126, 1709, 1677, 1600, 1465, 1385, 1301, 1180, 1022, 1011, 791, 762; HRMS (ESI+): m/z calcd for C16H15N4O3+ [M + H]+ 311.1139, found 311.1138. 3-(4-(Hydroxymethyl)-1H-1,2,3-triazol-1-yl)-3-phenyl- 1-(prop-2-ynyl)quinoline-2,4(1H,3H)-dione (5b). Color- less crystals, mp 141–148 °C (ethyl acetate); Rf = 0.21 (5% ethanol in chloroform); Rf = 0.46 (10% ethanol in chloro- form); 1H NMR (500 MHz, CDCl3) δ 2.34 (t, 1H, J = 2.5 Hz), 2.35–2.41 (m, 1H), 4.48 (dd, 1H, J = 17.8, 2.4 Hz), 4.71–4.79 (m, 2H), 5.33 (dd, 1H, J = 17.8, 2.4 Hz), 7.05 (s, 1H), 7.22 (ddd, 1H, J = 7.6, 7.5, 0.9 Hz), 7.33 (d, 1H, J = 8.3 Hz), 7.41–7.50 (m, 5H), 7.65 (ddd, 1H, J = 8.3, 7.4, 1.7 Hz), 8.03 (dd, 1H, J = 7.8, 1.6 Hz); 13C NMR (126 MHz, CDCl3) δ 33.6, 56.8, 73.6, 79.7, 115.8, 120.9, 124.6, 128.9, 129.2, 129.7, 130.1, 131.3, 136.9, 140.5, 145.8, 165.7, 187.5; IR (cm–1): ν 3273, 3158, 2125, 1715, 1682, 1602, 1468, 1374, 1302, 1175, 1044, 871, 761; HRMS (ESI+): m/z calcd for C21H17N4O3+ [M + H]+ 373.1295, found 373.1291. 1-((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)-3-(4-(hy- droxymethyl)-1H-1,2,3-triazol-1-yl)-3-methylquinoline- 2,4(1H,3H)-dione (6a). Colorless powder, mp 69–98 °C; Rf = 0.24 (5% ethanol in chloroform), Rf = 0.11 (3% etha- nol in chloroform); 1H NMR (500 MHz, CDCl3), δ 2.11 (s, 3H, CH3), 2.59 (s, 1H, OH), 4.80 (s, 2H, OCH2), 5.29 (d, 1H, J = 15.8 Hz, N-1–CHα), 5.33 (d, 1H, J = 15.8 Hz, N-1–CHβ), 5.44 (d, 1H, J = 14.8 Hz, N-1C–CHα), 5.50 (d, 1H, J = 14.8 Hz, N-1C–CHβ), 7.19–7.28 (m, 3H, H2D, H-6D, H-6), 7.29–7.38 (m, 3H, H-3D, H-4D, H-5D), 7.56 (s, 1H, H-5C), 7.67–7.74 (m, 2H, H-7, H-5A), 7.79 (d, 1H, J = 8.4 Hz, H-8), 7.99 (dd, 1H, J = 7.8, 1.6 Hz, H-5); 13C NMR (126 MHz, CDCl3) δ 23.5 (CH3), 39.5 (N-1–CH2), 54.5 (N-1C–CH2), 56.9 (OCH2), 71.7 (C-3), 116.9 (C-8), 119.2 (C-4a), 122.1 (C-5A), 123.5 (C-5C), 124.6 (C-6), 128.2 (C- 2D, C-6D), 129.0 (C-5), 129.3 (C-4D), 129.3 (C-3D, C-5D), 134.4 (C-1D), 137.7 (C-7), 141.7 (C-8a), 142.9 (C-4C), 147.3 (C-4A), 168.3 (C-2), 189.6 (C-4); 15N NMR (51 MHz, CDCl3) δ 138.6 (N-1), 247.1 (N-1A), 250.4 (N-1C), 349.3 (N-3C), 350.4 (N-3A), 361.6 (N-2C), 362.1 (N-2A); IR (cm–1): ν 3413, 3141, 1714, 1678, 1602, 1470, 1384, 1185, 1051, 793, 762, 722, 664; HRMS (ESI+): m/z calcd for C23H22N7O3+ [M + H]+ 444.1779, found 444.1773. 3-(4-(Hydroxymethyl)-1H-1,2,3-triazol-1-yl)-3-methyl- 1-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)quino- line-2,4(1H,3H)-dione (6b). Colorless powder, mp 96– 115 °C; Rf = 0.41 (10% ethanol in chloroform), Rf = 0.17 (5% ethanol in chloroform); 1H NMR (500 MHz, CDCl3) δ 2.17 (s, 3H, CH3), 2.65 (s, 1H, OH), 4.82 (s, 2H, OCH2), 5.37 (d, 1H, J = 15.8 Hz, N-1–CHα), 5.48 (d, 1H, J = 15.8 Hz, N-1–CHβ), 7.22–7.27 (m, 1H, H-6), 7.39-7.44 (m, 1H, H-4D), 7.46–7.52 (m, 2H, H-3D, H-5D), 7.68–7.75 (m, 3H, H-2D, H-6D, H-7), 7.76 (s, 1H, H-5A), 7.82 (d, 1H, J = 8.4 Hz, H-8), 8.01 (dd, 1H, J = 7.8, 1.6 Hz, H-5), 8.09 (s, 1H, H-5C); 13C NMR (126 MHz, CDCl3) δ 23.4 (CH3), 39.5 (N-1–CH2), 56.9 (OCH2), 71.6 (C-3), 116.8 (C-8), 119.2 (C-4a), 120.6 (C-2D, C-6D), 121.8 (C-5C), 122.1 (C-5A), 124.6 (C-6), 129.1 (C-4D), 129.4 (C-5), 129.9 (C-3D, C-5D), 136.9 (C-1D), 137.8 (C-7), 141.7 (C-8a), 143.2 (C-4C), 147.3 (C-4A), 168.4 (C-2), 189.5 (C-4); 15N NMR (51 MHz, CDCl3) δ 138.5 (N-1), 247.4 (N-1A), 256.2 (N-1C), 350.8 (N-3A), 351.6 (N-3C); IR (cm–1): ν 3400, 3143, 1715, 1678, 1601, 1470, 1384, 1303, 1233, 1183, 1047, 760, 690, 663; HRMS (ESI+): m/z calcd for C22H20N7O3+ [M + H]+ 430.1622, found 430.1614. 3-(4-(Hydroxymethyl)-1H-1,2,3-triazol-1-yl)-3-methyl- 1-((1-(pyridin-2-yl)-1H-1,2,3-triazol-4-yl)methyl)quin- oline-2,4(1H,3H)-dione (6c). Colorless powder, mp 66–89 °C; Rf = 0.32 (10% ethanol in chloroform), Rf = 0.09 (5% ethanol in chloroform); 1H NMR (500 MHz, CDCl3) δ 2.19 (s, 3H, CH3), 2.32 (s, 1H, OH), 4.83 (s, 2H, OCH2), 5.36 (d, 1H, J = 15.9 Hz, N-1–CHα), 5.52 (d, 1H, J = 15.9 Hz, N-1–CHβ), 7.23 (ddd, 1H, J = 7.7, 7.3, 1.0 Hz, H-6), 7.30–7.37 (m, 1H, H-5D), 7.71 (ddd, 1H, J = 8.5, 7.2, 1.6 Hz, 428 Acta Chim. Slov. 2020, 67, 421–434 Milićević et al.: Preparation of Quinoline-2,4-dione Functionalized ... H-7), 7.75–7.78 (m, 2H, H-5A, H-8), 7.87–7.92 (m, 1H, H-4D), 8.01 (dd, 1H, J = 7.7, 1.6 Hz, H-5), 8.10–8.15 (m, 1H, H-3D), 8.45-8.49 (m, 1H, H-6D), 8.58 (s, 1H, H-5C); 13C NMR (126 MHz, CDCl3) δ 23.7 (CH3), 39.4 (N-1–CH2), 56.9 (OCH2), 72.0 (C-3), 113.9 (C-3D), 116.6 (C-8), 119.3 (C-4a), 120.9 (C-5C), 122.3 (C-5A), 124.0 (C-5D), 124.6 (C-6), 129.3 (C-5), 137.6 (C-7), 139.3 (C-4D), 141.6 (C-8a), 143.0 (C-4C), 147.4 (C-4A), 148.8 (C-6D), 149.0 (C-2D), 168.3 (C-2), 189.6 (C-4); 15N NMR (51 MHz, CDCl3) δ 137.7 (N-1), 246.7 (N-1A), 259.9 (N-1C), 283.6 (N-1D), 350.3 (N-3A), 355.0 (N-3C); IR (cm–1): ν 3379, 3132, 1715, 1679, 1600, 1471, 1384, 1298, 1234, 1183, 1040, 782, 755, 658; HRMS (ESI+): m/z calcd for C21H19N8O3+ [M + H]+ 431.1575, found 431.1579. 1-((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)-3-(4-(hy- droxymethyl)-1H-1,2,3-triazol-1-yl)-3-phenylquinoline- 2,4(1H,3H)-dione (6d). Colorless powder, mp 93–121 °C; Rf = 0.23 (5% ethanol in chloroform); 1H NMR (500 MHz, CDCl3) δ 2.34 (t, 1H, J = 5.6 Hz, OH), 4.75 (d, 2H, J = 4.6 Hz, OCH2), 5.20 (d, 1H, J = 15.6 Hz, N-1C–CHα), 5.43 (d, 1H, J = 14.8 Hz, N-1–CHα), 5.49 (d, 1H, J = 15.6 Hz, N-1C–CHβ), 5.54 (d, 1H, J = 14.8 Hz, N-1–CHβ), 7.03 (s, 1H, H5A), 7.17 (ddd, 1H, J = 7.9, 7.2, 0.8 Hz, H-6), 7.23- 7.28 (m, 4H, H-2D, H-3D, H-5D, H-6D), 7.29–7.32 (m, 2H, H-2B, H-6B), 7.34–7.42 (m, 4H, H-3B, H-4B, H-5B, H-4D), 7.59 (s, 1H, H5C), 7.62 (ddd, 1H, J = 7.9, 7.9, 1.6 Hz, H-7), 7.74 (d, 1H, J = 8.4 Hz, H-8), 7.98 (dd, 1H, J = 7.7, 1.6 Hz, H-5); 13C NMR (126 MHz, CDCl3) δ 13C NMR (126 MHz, CDCl3) δ 39.9 (N-1C–CH2), 54.5 (N-1–CH2), 56.9 (OCH2), 79.6 (C-3), 116.8 (C-8), 120.9 (C-4a), 123.6 (C-5C), 124.5 (C-5A), 124.5 (C-6), 128.3 (C-2D, C-6D), 128.8 (C-2B, C-6B), 129.0 (C-5), 129.0 (C-4B), 129.3 (C-3B, C-5B), 129.9 (C-1D), 130.0 (C-3D, C-5D), 131.2 (C-4D), 134.5 (C-1B), 137.2 (C-7), 141.1 (C-8a), 142.9 (C-4C), 145.8 (C-4A), 166.6 (C-2), 188.0 (C-4); 15N NMR (51 MHz, CDCl3) δ 140.4 (N-1), 248.9 (N-1A), 250.6 (N-1C), 350.0 (N-3C), 352.8 (N-3A), 362.8 (N-2C), 364.9 (N-2A); IR (cm–1): ν 3391, 3141, 1715, 1678, 1601, 1469, 1450, 1376, 1049, 1032, 871, 761, 665, 608; HRMS (ESI+): m/z calcd for C28H24N7O3+ [M + H]+ 506.1935, found 506.1937. 3-(4-(Hydroxymethyl)-1H-1,2,3-triazol-1-yl)-3-phenyl- 1-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)quino- line-2,4(1H,3H)-dione (6e). Colorless powder, mp 118– 131 °C; Rf = 0.35 (5% ethanol in chloroform), Rf = 0.22 (3% ethanol in chloroform); 1H NMR (500 MHz, CDCl3) δ 2.33 (s, 1H, OH), 4.78 (s, 2H, OCH2), 5.41 (d, 1H, J = 15.7 Hz, N-1–CHα), 5.53 (d, 1H, J = 15.7 Hz, N-1–CHβ), 7.09 (s, 1H, H-5A), 7.20 (ddd, 1H, J = 7.9, 7.2, 0.7 Hz, H-6), 7.38–7.48 (m, 6H, H-2B, H-3B, H-4B, H-5B, H-6B, H-4D), 7.49–7.55 (m, 2H, H-3D, H-5D), 7.65 (ddd, 1H, J = 8.7, 7.1, 1.7 Hz, H-7), 7.68–7.72 (m, 2H, H2D, H-6D), 7.75 (d, 1H, J = 8.4 Hz, H-8), 8.02 (dd, 1H, J = 7.8, 1.5 Hz, H-5), 8.07 (s, 1H, H5C); 13C NMR (126 MHz, CDCl3) δ 39.8 (N-1–CH2), 56.9 (OCH2), 79.6 (C-3), 116.7 (C-8), 120.7 (C-2D, C-6D), 120.9 (C-4a), 121.8 (C-5C), 124.6 (C-5A), 124.6 (C-6), 128.9 (C-2B, C-6B), 129.1 (C-5), 129.2 (C-4D), 130.0 (C-1B), 130.0 (C-3D, C-5D), 130.1 (C-3B, C-5B), 131.3 (C-4B), 136.9 (C-1D), 137.3 (C-7), 140.9 (C-8a), 143.2 (C- 4C), 145.8 (C-4A), 166.9 (C-2), 188.0 (C-4); 15N NMR (51 MHz, CDCl3) δ 139.5 (N-1), 249.0 (N-1A), 256.2 (N-1C), 352.6 (N-3C), 353.0 (N-3A); IR (cm–1): ν 3401, 3144, 1716, 1679, 1600, 1501, 1468, 1449, 1377, 1044, 871, 760, 692; HRMS (ESI+): m/z calcd for C27H22N7O3+ [M + H]+ 492.1779, found 492.1768. 3-(4-(Hydroxymethyl)-1H-1,2,3-triazol-1-yl)-3-phenyl- 1-((1-(pyridin-2-yl)-1H-1,2,3-triazol-4-yl)methyl)quin- oline-2,4(1H,3H)-dione (6f). Colorless powder, mp 185– 194 °C; Rf  =  0.37 (5% ethanol in chloroform); 1H NMR (400 MHz, CDCl3) δ 2.38 (s, 1H, OH), 4.77 (s, 2H, OCH2), 5.28 (d, 1H, J = 15.8 Hz, N-1–CHα), 5.69 (d, 1H, J = 15.8 Hz, N-1–CHβ), 7.09 (s, 1H, H-5A), 7.17 (ddd, 1H, J = 7.7, 7.3, 1.0 Hz, H-6), 7.32–7.48 (m, 6H, H-5D, H-2B, H-3B, H-4B, H-5B, H-6B), 7.61 (ddd, 1H, J = 8.4, 7.2, 1.7 Hz, H-7), 7.68 (d, 1H, J = 8.3 Hz, H-8), 7.86–7.94 (m, 1H, H-4D), 8.01 (dd, 1H, J = 7.8, 1.5 Hz, H-5), 8.11–8.16 (m, 1H, H-3D), 8.47–8.51 (m, 1H, H-6D), 8.61 (s, 1H, H-5C); 13C NMR (100 MHz, CDCl3) δ 39.9 (N-1–CH2), 56.9 (OCH2), 79.7 (C-3), 113.9 (C-3D), 116.6 (C-8), 121.0 (C-4a), 121.0 (C-5C), 124.0 (C-5D), 124.5 (C-6), 124.5 (C-5A), 128.9 (C- 2B, C-6B), 129.0 (C-5), 130.0 (C-1B), 130.1 (C-3B, C-5B), 131.2 (C-4B), 137.1 (C-7), 139.3 (C-4D), 141.2 (C-8a), 143.0 (C-4C), 145.9 (C-4A), 148.9 (C-6D), 149.0 (C-2D), 166.7 (C-2), 188.0 (C-4); IR (cm–1): ν 3401, 3156, 1716, 1680, 1599, 1469, 1375, 1313, 1034, 999, 779, 760, 695, 683; HRMS (ESI+): m/z calcd for C26H21N8O3+ [M + H]+ 493.1731, found 493.1732. General procedure for the preparation of aldehydes 7a,b, 8a,b and 9a-f using PCC as the reagent. To a vigor- ously stirred solution of suitable alcohol (1 mmol) in di- chloromethane or acetone (15 mL), PCC (259 mg; 1.2 mmol) was added and the reaction mixture was stirred at the reflux temperature unless otherwise stated. Obtained reaction mixture was then stirred at the reflux temperature for up to one hour. The original orange color of mixture changed to almost black. Resulting solution with the sticky sediment was poured into a narrow (1 cm in diameter) column of silica gel (13 g). The organic portion was eluted with 5% ethanol in chloroform (approximately 350 mL). Volatile components of dark yellow eluate were evaporated in vacuo and obtained residue was chromatographed on a column of silica-gel (35 g) using 50% or 67% ethyl acetate in petroleum ether. Some crude products were further crystalized from ethyl acetate or benzene. For the reaction conditions and yields see Table 2 or Table 3, respectively. General procedure for the preparation of aldehydes 7a,b using Swern reaction. To a dry 25 mL evacuated flask, ox- alyl chloride (155 μL; 1.8 mmol) and dry tetrahydrofurane 429Acta Chim. Slov. 2020, 67, 421–434 Milićević et al.: Preparation of Quinoline-2,4-dione Functionalized ... (THF) were added. The flask was equipped with nitrogen gas inlet and cooled to –70 °C using dry ice–ethanol bath. Afterwards, DMSO (280 μL) was added dropwise and ob- tained solution was stirred for 60 minutes, keeping the temperature bellow –65 °C. Then, suitable mono-triazole alcohol 4 (1.5 mmol) dissolved in dry dichloromethane or acetone (11 mL) was added and stirring was continued for 90 minutes. Finally, after addition of DIPEA (1.275 mL; 7.32 mmol), the content of the flask was stirred for addi- tional 2 hours and tempered to the lab temperature. The reaction mixture was diluted with distilled water (10 mL) and extracted with dichloromethane (3x 20 mL). Com- bined organic phases were washed with ice-cold water (4x 20 mL), dried over anhydrous Na2SO4, filtered and volatile components were evaporated in vacuo. Obtained oily crude product was purified on silica-gel column, using 38% ethyl acetate in petroleum ether as mobile phase. To that way gained oily product, diethyl ether was added and it was cooled to –20 °C to provide solid compound that was filtered through the sintered glass filter and dried at 50 °C. For the yields of products see Table 2. General procedure for the synthesis of aldehydes using MnO2 as a reagent. To a vigorously stirred solution of suitable alcohol (1 mmol) in acetone (10 mL), MnO2 (869 mg; 10 mmol) was added. Obtained reaction mixture was then stirred at the reflux temperature unless otherwise stated. Resulting black suspension was filtered through the filter paper and volatile components of the filtrate were evaporated in vacuo. Residual crude oily product was chromatographed on silica-gel column, using 50% ethyl acetate in petroleum ether as mobile phase. Some that way obtained TLC and IR pure products were further crystal- ized from ethyl acetate. For the reaction conditions and yields see Table 2 or Table 3, respectively. 1-(1,2,3,4-Tetrahydro-3-methyl-2,4-dioxoquino- lin-3-yl)-1H-1,2,3-triazole-4-carbaldehyde (7a). Color- less crystals, mp 267–271 °C (ethyl acetate); Rf = 0.54 (10% ethanol in chloroform); 1H NMR (500 MHz, DMSO-d6) δ 2.16 (s, 3H, CH3), 7.23 (d, 1H, J = 7.7 Hz, H-8), 7.21–7.27 (m, 1H, H-6), 7.75 (ddd, 1H, J = 7.8, 7.7, 1.5 Hz, H-7), 7.85 (dd, 1H, J = 7.8, 1.7 Hz, H-5), 9.18 (s, 1H, H-5A), 10.08 (s, 1H, CHO), 11.50 (s, 1H, H-1); 13C NMR (126 MHz, DMSO-d6) δ 23.4 (CH3), 73.6 (C-3), 117.0 (C-8), 117.6 (C- 4a), 123.5 (C-6), 127.6 (C-5), 129.6 (C-5A), 137.2 (C-7), 141.4 (C-8a), 146.6 (C-4A), 168.3 (C-2), 185.1 (CHO), 190.3 (C-4); 15N NMR (51 MHz, DMSO-d6) δ 133.4 (N-1), 252.0 (N-1A), 358.6 (N-3A), 367.9 (N-2A); IR (cm–1): ν 3308, 3140, 2851, 1716, 1680, 1614, 1531, 1484, 1378, 1345, 1231, 1211, 816, 757, 667; HRMS (ESI+): m/z calcd for C13H11N4O3+ [M + H]+ 271.0826, found 271.0833. 1-(1,2,3,4-Tetrahydro-2,4-dioxo-3-phenylquinolin-3-yl)- 1H-1,2,3-triazole-4-carbaldehyde (7b). Colorless crys- tals, mp 188–191 °C (ethyl acetate); Rf = 0.36 (5% ethanol in chloroform), Rf  =  0.35 (30% ethyl acetate in chloro- form); 1H NMR (500 MHz, DMSO-d6) δ 7.09 (d, 1H, J = 8.0 Hz, H-8), 7.17 (ddd, 1H, J = 7.6, 7.6, 1.0 Hz, H-6), 7.34–7.41 (m, 2H, H-2B, H-6B), 7.47–7.54 (m, 3H, H-3B, H-4B, H-5B), 7.63 (ddd, 1H, J = 8.2, 7.3, 1.6 Hz, H-7), 7.85 (dd, 1H, J = 7.8, 1.4 Hz, H-5), 8.93 (s, 1H, H-5A), 10.05 (s, 1H, CHO), 11.68 (s, 1H, H-1); 13C NMR (126 MHz, DMSO-d6) δ 80.7 (C-3), 116.7 (C-8), 119.5 (C-4a), 123.5 (C-6), 127.5 (C-5), 128.9 (C-2B, C-6B), 129.7 (C-3B, C-5B), 129.7 (C-1B), 130.7 (C-4B), 130.7 (C-5A), 136.8 (C-7), 140.4 (C-8a), 146.2 (C-4A), 166.6 (C-2), 185.1 (CHO), 188.4 (C-4); 15N NMR (51 MHz, DMSO-d6) δ 134.8 (N-1), 249.8 (N-1A), 351.6 (N-3A), 356.4 (N-2A); IR (cm–1): ν 3253, 2914, 2860, 1723, 1689, 1615, 1595, 1486, 1355, 1208, 1045, 857, 780, 752, 697; HRMS (ESI+): m/z calcd for C18H13N4O3+ [M + H]+ 333.0982, found 333.0988. 1-(1,2,3,4-Tetrahydro-3-methyl-2,4-dioxo-1-(prop-2- ynyl)quinolin-3-yl)-1H-1,2,3-triazole-4-carbaldehyde (8a). Colorless crystals, mp 189–194  °C (benzene); Rf = 0.40 (5% ethanol in chloroform); Rf = 0.63 (10% etha- nol in chloroform); 1H NMR (500 MHz, CDCl3) δ 2.23 (s, 3H), 3.32–3.37 (m, 1H), 4.66 (dd, 1H, J = 17.9, 1.6 Hz), 5.11 (dd, 1H, J = 17.9, 1.6 Hz), 7.30–7.37 (m, 1H), 7.47 (d, 1H, J = 8.4 Hz), 7.81 (ddd, 1H, J = 8.4, 7.3, 1.5 Hz), 8.09 (d, 1H, J = 7.7 Hz), 8.31 (s, 1H), 10.18 (s, 1H);13C NMR (126 MHz, CDCl3) δ 23.9, 33.2, 72.8, 73.9, 76.7, 116.3, 119.2, 124.9, 126.3, 129.6, 137.7, 140.9, 147.1, 166.9, 185.1, 188.7; IR (cm–1): ν 3282, 3150, 2125, 1704, 1673, 1601, 1528, 1470, 1444, 1381, 1306, 1206, 798, 761; HRMS (ESI+): m/z calcd for C16H13N4O3+ [M + H]+ 309.0982, found 309.0979. Anal. Calcd for C16H12N4O (308.29): C 62.33, H 3.92, N 18.17; found: C 62.26, H 4.22, N 17.92. 1-(1,2,3,4-Tetrahydro-2,4-dioxo-3-phenyl-1-(prop-2- ynyl)quinolin-3-yl)-1H-1,2,3-triazole-4-carbaldehyde (8b). Colorless crystals, mp 176–182  °C (benzene); Rf = 0.68 (5% ethanol in chloroform); Rf = 0.51 (30% ethyl acetate in chloroform); 1H NMR (500 MHz, CDCl3) δ 2.33-2.37 (m, 1H), 4.52 (dd, 1H, J = 17.8, 1.4 Hz), 5.34 (dd, 1H, J = 17.8, 1.4  Hz), 7.22–7.28 (m, 1H), 7.33-7.38 (m, 1H), 7.44–7.55 (m, 5H), 7.61 (s, 1H), 7.64–7.71 (m, 1H), 8.05 (d, 1H, J = 7.7 Hz), 10.13 (s, 1H); 13C NMR (126 MHz, CDCl3) δ 33.7, 73.8, 76.6, 80.2, 116.0, 120.8, 124.8, 128.5, 128.8, 129.0, 129.2, 130.5, 131.8, 137.2, 140.4, 145.8, 165.1, 185.2, 186.9; IR (cm–1): ν 3237, 3151, 2124, 1716, 1682, 1603, 1469, 1373, 1301, 1200, 1170, 1042, 774, 692; HRMS (ESI+): m/z calcd for C21H15N4O3+ [M + H]+ 371.1139, found 371.1130. 1-(1-((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)-1,2,3,4 -tetrahydro-3-methyl-2,4-dioxoquinolin-3-yl)-1H-1,2,3 -triazole-4-carbaldehyde (9a). Colorless powder, mp 63– 87 °C; Rf  =  0.48 (5  % ethanol in chloroform); Rf  =  0.13 (50% ethyl acetate in petroleum ether); Rf = 0.28 (33% pe- troleum ether in ethyl acetate); 1H NMR (500 MHz, 430 Acta Chim. Slov. 2020, 67, 421–434 Milićević et al.: Preparation of Quinoline-2,4-dione Functionalized ... CDCl3), δ 2.16 (s, 3H, CH3), 5.28 (d, 1H, J = 15.7 Hz, N-1–CHα), 5.37 (d, 1H, J = 15.7 Hz, N-1–CHβ), 5.45 (d, 1H, J = 14.8 Hz, N-1C–CHα), 5.50 (d, 1H, J = 14.8 Hz, N-1C–CHβ), 7.21–7.26 (m, 2H, H-2D, H-6D), 7.27 (ddd, 1H, J = 7.6, 7.5, 0.9 Hz, H-6), 7.31–7.38 (m, 3H, H-3D, H-4D, H-5D), 7.53 (s, 1H, H-5C), 7.75 (ddd, 1H, J = 8.4, 7.4, 1.7 Hz, H-7), 7.86 (d, 1H, J = 8.4 Hz, H-8), 8.02 (dd, 1H, J = 7.8, 1.6 Hz, H-5), 8.30 (s, 1H, H-5A), 10.15 (s, 1H, CHO); 13C NMR (126 MHz, CDCl3) δ 23.8 (CH3), 39.5 (N-1– CH2), 54.5 (N-1C–CH2), 72.6 (C-3), 117.0 (C-8), 119.0 (C-4a), 123.4 (C-5C), 124.8 (C-6),126.3 (C-5A), 128.2 (C- 2D, C-6D), 129.0 (C-4D), 129.3 (C-3D, C-5D), 129.3 (C-5), 134.3 (C-1D), 138.0 (C-7), 141.5 (C-8a), 142.7 (C-4C), 147.0 (C-4A), 167.7 (C-2), 185.0 (CHO), 188.9 (C-4); 15N NMR (51 MHz, CDCl3) δ 138.4 (N-1), 250.6 (N-1C), 251.7 (N-1A), 350.0 (N-3C), 361.8 (N-2A), 362.6 (N-2C); IR (cm–1): ν 3137, 2929, 2852, 1681, 1601, 1470, 1385, 1211, 1186, 1048, 799, 763, 721, 686, 663; HRMS (ESI+): m/z cal- cd for C23H20N7O3+ [M + H]+ 442.1622, found 442.1620. 1-(1,2,3,4-Tetrahydro-3-methyl-2,4-dioxo-1-((1-phenyl- 1H-1,2,3-triazol-4-yl)methyl)quinolin-3-yl)-1H-1,2,3- triazole-4-carbaldehyde (9b). Colorless powder, mp 71– 93 °C; Rf  =  0.44 (33% petroleum ether in ethyl acetate); Rf = 0.40 (5% ethanol in chloroform); 1H NMR (500 MHz, CDCl3) δ 2.22 (s, 3H, CH3), 5.45 (s, 2H, N-1–CH2), 7.29 (ddd, 1H, J = 7.6, 7.5, 0.9 Hz, H-6), 7.41–7.46 (m, 1H, H-4D), 7.48–7.53 (m, 2H, H-3D, H-5D), 7.68–7.72 (m, 2H, H-2D, H-6D), 7.78 (ddd, 1H, J = 8.4, 7.4, 1.7 Hz, H-7), 7.90 (d, 1H, J = 8.4 Hz, H-8), 8.04 (dd, 1H, J = 7.9, 1.6 Hz, H-5), 8.05 (s, 1H, H-5C), 8.36 (s, 1H, H-5A), 10.17 (s, 1H, CHO) 13C NMR (126 MHz, CDCl3) δ 23.8 (CH3), 39.5 (N-1–CH2), 72.5 (C-3), 117.0 (C-8), 119.0 (C-4a), 120.6 (C-2D, C-6D), 121.8 (C-5C), 124.9 (C-6), 126.2 (C-5A), 129.2 (C-4D), 129.4 (C-5), 130.0 (C-3D, C-5D), 136.8 (C-1D), 138.1 (C-7), 141.5 (C-8a), 143.0 (C-4C), 147.0 (C-4A), 167.8 (C-2), 185.0 (CHO), 188.8 (C-4); 15N NMR (51 MHz, CDCl3) δ 138.5 (N-1), 251.6 (N-1A), 256.2 (N-1C), 352.0 (N-3C), 362.2 (N-2A); IR (cm–1): ν 3138, 2928, 2853, 1682, 1601, 1470, 1385, 1212, 1185, 1046, 760, 690, 663; HRMS (ESI+): m/z calcd for C22H18N7O3+ [M + H]+ 428.1466, found 428.1461. 1-(1,2,3,4-Tetrahydro-3-methyl-2,4-dioxo-1-((1-(pyri- din-2-yl)-1H-1,2,3-triazol-4-yl)methyl)quinolin-3-yl)- 1H-1,2,3-triazole-4-carbaldehyde (9c). Colorless powder, mp 47–65 °C; Rf = 0.12 (30% ethyl acetate in chloroform); Rf = 0.34 (5% ethanol in chloroform); 1H NMR (500 MHz, CDCl3) δ 2.24 (s, 3H, CH3), 5.35 (d, 1H, J = 15.9 Hz, N-1– CHα), 5.58 (d, 1H, J = 15.9 Hz, N-1–CHβ), 7.24–7.31 (m, 1H, H-6), 7.32–7.38 (m, 1H, H-5D), 7.76 (ddd, 1H, J = 8.4, 7.3, 1.7 Hz, H-7), 7.83 (d, 1H, J = 8.4 Hz, H-8), 7.88-7.93 (m, 1H, H-4D), 8.04 (dd, 1H, J = 7.8, 1.6 Hz, H-5), 8.11- 8.16 (m, 1H, H-3D), 8.35 (s, 1H, H-5A), 8.46-8.49 (m, 1H, H-6D), 8.59 (s, 1H, H-5C), 10.18 (s, 1H, CHO); 13C NMR (126 MHz, CDCl3) δ 24.0 (CH3), 39.4 (N-1–CH2), 72.9 (C-3), 113.9 (C-3D), 116.8 (C-8), 119.1 (C-4a), 120.8 (C-5C), 124.1 (C-5D), 124.8 (C-6), 126.4 (C-5A), 129.4 (C- 5), 137.9 (C-7), 139.3 (C-4D), 141.6 (C-8a), 142.8 (C-4C), 147.1 (C-4A), 148.8 (C-6D), 148.9 (C-2D), 167.7 (C-2), 185.1 (CHO), 189.0 (C-4); 15N NMR (51 MHz, CDCl3) δ 137.8 (N-1), 251.1 (N-1A), 261.0 (N-1C), 283.9 (N-1D), 355.3 (N-3C), 361.8 (N-2A); IR (cm–1): ν 3138, 2929, 2854, 1683, 1600, 1471, 1385, 1211, 1184, 1038, 999, 781, 760, 663; HRMS (ESI+): m/z calcd for C21H17N8O3+ [M + H]+ 429.1418, found 429.1431. 1-(1-((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)-1,2,3,4- tetrahydro-2,4-dioxo-3-phenylquinolin-3-yl)-1H-1,2,3- triazole-4-carbaldehyde (9d). Colorless powder, mp 87– 113  °C; Rf  =  0.58 (5% ethanol in chloroform); Rf  =  0.40 (33% petroleum ether in ethyl acetate); 1H NMR (500 MHz, CDCl3) δ 5.20 (d, 1H, J = 15.6 Hz, N-1–CHα), 5.44 (d, 1H, J = 14.8 Hz, N-1C–CHα), 5.53 (d, 1H, J = 15.6 Hz, N-1–CHβ), 5.56 (d, 1H, J = 14.8 Hz, N-1C–CHβ), 7.20 (ddd, 1H, J = 7.6, 7.5, 0.8 Hz, H-6), 7.26–7.28 (m, 4H, H-3B, H-5B, H-3D, H-5D), 7.28-7.30 (m, 2H, H-2B, H-6B), 7.37–7.40 (m, 3H, H-2D, H-6D, H-4B), 7.41–7.47 (m, 1H, H4D), 7.58 (s, 1H, H-5C), 7.58 (s, 1H, H-5A), 7.65 (ddd, 1H, J = 8.4, 7.4, 1.7 Hz, H-7), 7.78 (d, 1H, J = 8.4 Hz, H-8), 8.00 (dd, 1H, J = 7.7, 1.6 Hz, H-5), 10.13 (s, 1H, CHO); 13C NMR (126 MHz, CDCl3) δ 40.0 (N-1–CH2), 54.5 (N-1C– CH2), 80.1 (C-3), 117.0 (C-8), 120.7 (C-4a), 123.5 (C-5C), 124.8 (C-6), 128.3 (C-3B, C-5B), 128.4 (C-5A), 128.6 (C-3D, C-5D), 129.0 (C-5), 129.0 (C-1B), 129.1 (C4B), 129.4 (C-2D, C-6D), 130.4 (C-2B, C-6B), 131.7 (C-4D), 134.4 (C-1D), 137.5 (C-7), 141.0 (C-8a), 142.7 (C-4C), 145.8 (C-4A), 165.9 (C-2), 185.2 (CHO), 187.3 (C-4); 15N NMR (51 MHz, CDCl3) δ 140.0 (N-1), 250.6 (N-1C), 253.7 (N-1A), 350.8 (N-3C), 362.5 (N-2C); IR (cm–1): ν 3138, 2850, 1701, 1680, 1601, 1469, 1376, 1044, 871, 772, 748, 724, 696; HRMS (ESI+): m/z calcd for C28H22N7O3+ [M + H]+ 504.1779, found 504.1782. 1-(1,2,3,4-Tetrahydro-2,4-dioxo-3-phenyl-1-((1-phenyl- 1H-1,2,3-triazol-4-yl)methyl)quinolin-3-yl)-1H-1,2,3- triazole-4-carbaldehyde (9e). Colorless powder, mp 91– 122 °C; Rf  =  0.62 (5% ethanol in chloroform), Rf  =  0.29 (50% ethyl acetate in petroleum ether); 1H NMR (500 MHz, CDCl3) δ 5.41 (d, 1H, J = 15.7 Hz, N-1–CHα), 5.58 (d, 1H, J = 15.7 Hz, N-1–CHβ), 7.23 (ddd, 1H, J = 7.6, 7.5, 0.9 Hz, H-6), 7.41–7.43 (m, 2H, H-2B, H-6B), 7.43–7.45 (m, 2H, H-3B, H-5B), 7.45–7.48 (m, 1H, H-4D), 7.48–7.51 (m, 1H, H-4B), 7.51–7.55 (m, 2H, H-3D, H-5D), 7.64 (s, 1H, H-5A), 7.68 (ddd, 1H, J = 9.5, 7.4, 1.7 Hz, H-7), 7.69–7.72 (m, 2H, H-2D, H-6D), 7.79 (d, 1H, J = 8.4 Hz, H-8), 8.04 (dd, 1H, J = 7.8, 1.6 Hz, H-5), 8.06 (s, 1H, H-5C), 10.15 (s, 1H, CHO); 13C NMR (126 MHz, CDCl3) δ 39.8 (N-1– CH2), 80.1 (C-3), 116.8 (C-8), 120.7 (C-2D, C-6D), 120.7 (C-4a), 121.8 (C-5C), 124.8 (C-6), 128.4 (C-5A), 128.8 (C-2B, C-6B), 129.1 (C-1B), 129.2 (C-4D), 129.3 (C-5), 130.0 (C-3D, C-5D), 130.5 (C-3B, C-5B), 131.8 (C-4B), 136.8 431Acta Chim. Slov. 2020, 67, 421–434 Milićević et al.: Preparation of Quinoline-2,4-dione Functionalized ... (C-1D), 137.6 (C-7), 140.9 (C-8a), 143.0 (C-4C), 145.8 (C-4A), 166.2 (C-2), 185.1 (CHO), 187.2 (C-4); 15N NMR (51 MHz, CDCl3) δ 139.3 (N-1), 254.3 (N-1A), 256.1 (N- 1C), 256.1 (N-2C), 352.7 (N-3C), 363.4 (N-2A), IR (cm–1): ν 3141, 2848, 1701, 1682, 1600, 1468, 1376, 1306, 1042, 872, 772, 691, 665; HRMS (ESI+): m/z calcd for C27H20N7O3+ [M + H]+ 490.1622, found 490.1616. 1-(1,2,3,4-Tetrahydro-2,4-dioxo-3-phenyl-1-((1-(pyri- din-2-yl)-1H-1,2,3-triazol-4-yl)methyl)quinolin-3-yl)- 1H-1,2,3-triazole-4-carbaldehyde (9f). Colorless powder, mp 88–114 °C; Rf  =  0.44 (5% ethanol in chloroform), Rf = 0.23 (30% ethyl acetate in chloroform); 1H NMR (500 MHz, CDCl3) δ 5.31 (d, 1H, J = 15.8 Hz, N-1–CHα), 5.72 (d, 1H, J = 15.8 Hz, N-1–CHβ), 7.21 (ddd, 1H, J = 7.5, 7.5, 0.9 Hz, H-6), 7.35–7.39 (m, 1H, H-5D), 7.40–7.51 (m, 5H, H-2B, H-3B, H-4B, H-5B, H-6B), 7.62–7.68 (m, 2H, H-5A, H-7), 7.72 (d, 1H, J = 8.4 Hz, H-8), 7.89–7.95 (m, 1H, H-4D), 8.04 (dd, 1H, J = 7.8, 1.5 Hz, H-5), 8.13–8.17 (m, 1H, H-3D), 8.48-8.52 (m, 1H, H-6D), 8.63 (s, 1H, H-5C), 10.15 (s, 1H, CHO); 13C NMR (126 MHz, CDCl3) δ 39.9 (N-1–CH2), 80.2 (C-3), 113.9 (C-3D), 116.7 (C-8), 120.8 (C-4a), 120.9 (C-5C), 124.1 (C-5D), 124.8 (C-6), 128.4 (C- 5A), 128.8 (C-2B, C-6B), 129.0 (C-1B), 129.1 (C-5), 130.5 (C-3B, C-5B), 131.7 (C-4B), 137.4 (C-7), 139.3 (C-4D), 141.1 (C-8a), 142.8 (C-4C), 145.8 (C-4A), 148.9 (C-6D), 149.0 (C-2D), 165.9 (C-2), 185.2 (CHO), 187.3 (C-4); 15N NMR (51 MHz, CDCl3) δ 139.2 (N-1), 254.0 (N-1A), 260.2 (N-1C), 284.4 (N-1D), 355.5 (N-3C), 363.1 (N-2A); IR (cm– 1): ν 3153, 2852, 1700, 1681, 1599, 1470, 1375, 1313, 1035, 999, 776, 750, 696; HRMS (ESI+): m/z calcd for C26H- 19N8O3+ [M + H]+ 491.1575, found 491.1578. General procedure for the preparation of carboxylic ac- ids 10a,b, 11a,b and 12a-f. To a vigorously stirred ice- cooled solution of appropriate alcohol (1.00 mmol) in ace- tone, also ice-cooled solution of chromium(VI) oxide (2.4 g, 24 mmol unless otherwise stated) in 2m H2SO4 (24 mL unless otherwise stated) was added during 5 minutes and stirring was continued still for the time indicated in Table 4. The original intense red color of reaction mixture changed to black. After completion of reaction (TLC), eth- anol (15 mL) was added and the mixture was poured onto ice. After the ice melted, the solid phase was filtered off, washed with water and ethanol and dried at 50 °C afford- ing the first part of product. The filtrate was extracted with chloroform (up to 7 × 50 mL, until the product was detect- able in the extract by TLC), washed with water (100 mL), dried (Na2SO4) and filtered. From the filtrate, volatile components were evaporated in vacuo, whereby the sec- ond portion of crude product was obtained. In some cases, both parts of TLC and IR pure crude product were joined together and crystalized from ethyl acetate. 1-(1,2,3,4-Tetrahydro-3-methyl-2,4-dioxoquino- lin-3-yl)-1H-1,2,3-triazole-4-carboxylic acid (10a). Col- orless crystals, mp 198–201 °C (ethyl acetate); Rf = 0.05– 0.37 (50% ethanol in chloroform); 1H NMR (500 MHz, DMSO-d6) δ 2.14 (s, 3H, CH3), 7.22 (d, 1H, J = 7.9 Hz, H-8), 7.21–7.27 (m, 1H, H-6), 7.74 (ddd, 1H, J = 7.8, 7.7, 1.5 Hz, H-7), 7.84 (d, 1H, J = 7.6 Hz, H-5), 8.99 (s, 1H, H-5A), 11.45 (s, 1H, H-1), 13.21 (br, 1H, COOH); 13C NMR (126 MHz, DMSO-d6) δ 23.4 (CH3), 73.4 (C-3), 117.0 (C-8), 117.7 (C-4a), 123.4 (C-6), 127.6 (C-5), 130.4 (C-5A), 137.2 (C-7), 139.5 (C-4A), 141.5 (C-8a), 161.7 (COOH), 168.5 (C-2), 190.5 (C-4); 15N NMR (51 MHz, DMSO-d6) δ 133.2 (N-1), 250.2 (N-1A), 357.1 (N-3A), 367.5 (N-2A); IR (cm–1): ν 3436, 3141, 2927, 1718, 1684, 1614, 1485, 1392, 1361, 1260, 1163, 1020, 761, 665, 597; HRMS (ESI+): m/z calcd for C13H11N4O4+ [M + H]+ 287.0775, found 287.0777. 1-(1,2,3,4-Tetrahydro-2,4-dioxo-3-phenylquinolin-3-yl)- 1H-1,2,3-triazole-4-carboxylic acid (10b). Colorless crystals, mp 205–209 °C (ethyl acetate); Rf  =  0.00–0.19 (10% ethanol in chloroform); 1H NMR (500 MHz, DM- SO-d6) δ 7.07 (d, 1H, J = 8.0 Hz, H-8), 7.16 (ddd, 1H, J = 7.7, 7.5, 1.0 Hz, H-6), 7.32–7.40 (m, 2H, H-2B, H-6B), 7.45–7.53 (m, 3H, H-3B, H-4B, H-5B), 7.62 (ddd, 1H, J = 8.2, 7.3, 1.6 Hz, H-7), 7.83 (dd, 1H, J = 7.8, 1.4 Hz, H-5), 8.71 (s, 1H, H-5A), 11.63 (s, 1H, H-1), 13.06 (br, 1H, COOH); 13C NMR (126 MHz, DMSO-d6) δ 80.6 (C-3), 116.7 (C-8), 119.6 (C-4a), 123.4 (C-6), 127.4 (C-5), 128.9 (C-2B, C-6B), 129.6 (C-3B, C-5B), 129.8 (C-1B), 130.6 (C- 4B), 131.1 (C-5A), 136.7 (C-7), 139.2 (C-4A), 140.4 (C-8a), 161.7 (COOH), 166.8 (C-2), 188.6 (C-4); IR (cm–1): ν 3364, 3157, 1740, 1724, 1679, 1613, 1594, 1485, 1201, 1183, 1039, 855, 778, 754; HRMS (ESI+): m/z calcd for C18H13N4O4+ [M + H]+ 349.0931, found 349.0927. 1-(1,2,3,4-Tetrahydro-3-methyl-2,4-dioxo-1-(prop-2- ynyl)quinolin-3-yl)-1H-1,2,3-triazole-4-carboxylic acid (11a). Colorless crystals, mp 187–190  °C (ethyl acetate); Rf = 0.15 (50% ethanol in chloroform); 1H NMR (500 MHz, DMSO-d6) δ 2.14 (s, 3H), 3.38 (dd, 1H, J = 2.4, 2.3 Hz), 4.84 (dd, 1H, J = 18.1, 2.3 Hz), 4.97 (dd, 1H, J = 18.1, 2.4 Hz), 7.38 (dd, 1H, J = 7.7, 7.3 Hz), 7.59 (d, 1H, J = 8.5 Hz), 7.91 (ddd, 1H, J = 8.5, 7.3, 1.4 Hz), 7.97 (dd, 1H, J = 7.7, 1.4 Hz), 8.99 (s, 1H), 13.23 (br, 1H); 13C NMR (126 MHz, DMSO-d6) δ 23.5, 32.7, 73.7, 75.4, 78.2, 116.7, 119.2, 124.2, 128.1, 130.6, 137.1, 139.6, 140.7, 161.7, 167.7, 189.5; IR (cm–1): ν 3259, 3137, 2127, 1742, 1693, 1650, 1603, 1472, 1393, 1304, 1214, 1187, 1045, 781, 753; HRMS (ESI+): m/z calcd for C16H13N4O4+ [M + H]+ 325.0931, found 325.0930. 1-(1,2,3,4-Tetrahydro-2,4-dioxo-3-phenyl-1-(prop-2- ynyl)quinolin-3-yl)-1H-1,2,3-triazole-4-carboxylic acid (11b). Colorless crystals, mp 154–161 °C (ethyl acetate); Rf  =  0.23 (50% ethanol in chloroform); Rf  =  0.00–0.15 (10% ethanol in chloroform); 1H NMR (500 MHz, DMSO-d6) δ 3.40–3.44 (m, 1H), 4.80 (dd, 1H, J = 16.8, 3.3 Hz), 5.16 (dd, 1H, J = 16.8, 3.3 Hz), 7.23-7.32 (m, 3H), 432 Acta Chim. Slov. 2020, 67, 421–434 Milićević et al.: Preparation of Quinoline-2,4-dione Functionalized ... 7.39–7.53 (m, 4H), 7.75 (ddd, 1H, J = 8.4, 7.4, 1.7 Hz), 7.92 (dd, 1H, J = 7.7, 1.5 Hz), 8.79 (s, 1H), 13.23 (br, 1H); 13C NMR (126 MHz, DMSO-d6) δ 33.2, 75.5, 77.8, 80.5, 116.3, 121.0, 124.2, 127.8, 128.7, 129.5, 129.7, 130.7, 131.3, 136.7, 139.2, 139.9, 161.7, 165.7, 187.5; IR (cm–1): ν 3494, 3205, 2118, 1720, 1683, 1603, 1469, 1374, 1306, 1218, 1040, 871, 764, 696; HRMS (ESI+): m/z calcd for C21H15N4O4+ [M + H]+ 387.1088, found 387.1084. 1-(1-((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)-1,2,3,4 -tetrahydro-3-methyl-2,4-dioxoquinolin-3-yl)-1H -1,2,3-triazole-4-carboxylic acid (12a). Colorless solid, mp 129–148 °C; Rf  =  0.00–0.35 (10% ethanol in chloro- form); 1H NMR (500 MHz, DMSO-d6), δ 2.15 (s, 3H, CH3), 5.18 (d, 1H, J = 16.2 Hz, N-1–CHα), 5.48 (d, 1H, J = 16.2 Hz, N-1–CHβ), 5.57 (s, 2H, N-1C–CH2), 7.24–7.28 (m, 2H, H-2D, H-6D), 7.28–7.38 (m, 4H, H-6, H-3D, H-4D, H-5D), 7.64 (d, 1H, J = 8.5 Hz, H-8), 7.81 (ddd, 1H, J = 8.7, 7.1, 1.7 Hz, H-7), 7.93 (dd, 1H, J = 7.6, 1.2 Hz, H-5), 8.16 (s, 1H, H-5C), 8.96 (s, 1H, H-5A), 12.98 (br, 1H, COOH); 13C NMR (126 MHz, DMSO-d6) δ 23.6 (CH3), 38.9 (N-1– CH2), 52.9 (N-1C–CH2), 74.0 (C-3), 116.7 (C-8), 119.3 (C-4a), 123.9 (C-5C), 123.9 (C-6), 127.9 (C-2D, C-6D), 128.0 (C-4D), 128.2 (C-5),128.8 (C-3D, C-5D), 130.6 (C-5A), 136.0 (C-1D), 137.1 (C-7), 139.6 (C-4A), 141.4 (C-8a), 142.3 (C-4C), 161.7 (COOH), 168.2 (C-2), 189.8 (C-4); 15N NMR (51 MHz, DMSO-d6) δ 136.8 (N-1), 249.3 (N-1A), 251.2 (N-1C), 351.1 (N-3C), 357.4 (N-3A), 362.4 (N-2C), 367.7 (N-2A); IR (cm–1): ν 3468, 3140, 2945, 1716, 1679, 1602, 1470, 1385, 1278, 1222, 1045, 784, 764, 721; HRMS (ESI+): m/z calcd for C23H20N7O4+ [M + H]+ 458.1571, found 458.1579. 1-(1,2,3,4-Tetrahydro-3-methyl-2,4-dioxo-1-((1-phenyl- 1H-1,2,3-triazol-4-yl)methyl)quinolin-3-yl)-1H-1,2,3- triazole-4-carboxylic acid (12b). Colorless solid, mp 143– 168 °C; Rf  =  0.00–0.35 (10% ethanol in chloroform); Rf  =  0.18 (50% ethanol in chloroform); 1H NMR (500 MHz, DMSO-d6) δ 2.22 (s, 3H, CH3), 5.27 (d, 1H, J = 16.3 Hz, N-1–CHα), 5.62 (d, 1H, J = 16.3 Hz, N-1–CHβ), 7.34 (dd, 1H, J = 7.4, 7.4 Hz, H-6), 7.45–7.52 (m, 1H, H-4D), 7.55–7.62 (m, 2H, H-3D, H-5D), 7.69 (d, 1H, J = 8.4 Hz, H-8), 7.81–7.91 (m, 3H, H-7, H-2D, H-6D), 7.96 (d, 1H, J = 7.3 Hz, H-5), 8.74 (s, 1H, H-5C), 8.97 (s, 1H, H-5A), 13.02 (br, 1H, COOH); 13C NMR (126 MHz, DMSO-d6) δ 23.6 (CH3), 38.8 (N-1–CH2), 74.1 (C-3), 116.8 (C-8), 119.4 (C-4a), 120.2 (C-2D, C-6D), 121.8 (C-5C), 124.0 (C-6), 128.0 (C-5), 128.9 (C-4D), 130.0 (C-3D, C-5D), 130.6 (C- 5A), 136.5 (C-1D), 137.2 (C-7), 139.7 (C-4A), 141.5 (C-8a), 143.3 (C-4C), 161.7 (COOH), 168.3 (C-2), 189.9 (C-4); 15N NMR (51 MHz, DMSO-d6) δ 135.9 (N-1), 249.4 (N-1A), 255.8 (N-1C), 353.6 (N-3C), 356.9 (N-3A), 358.2 (N-2C), 367.2 (N-2A); IR (cm–1): ν 3142, 3085, 2925, 1717, 1679, 1601, 1470, 1386, 1278, 1226, 1193, 1045, 760, 690, 663; HRMS (ESI+): m/z calcd for C22H18N7O4+ [M + H]+ 444.1415, found 444.1413. 1-(1,2,3,4-Tetrahydro-3-methyl-2,4-dioxo-1-((1-(pyri- din-2-yl)-1H-1,2,3-triazol-4-yl)methyl)quinolin-3-yl)- 1H-1,2,3-triazole-4-carboxylic acid (12c). Colorless sol- id, mp 152–161 °C; Rf = 0.03 (10% ethanol in chloroform); Rf  =  0.14 (50% ethanol in chloroform); 1H NMR (500 MHz, DMSO-d6) δ 2.22 (s, 3H), 5.40 (d, 1H, J = 16.5 Hz), 5.55 (d, 1H, J = 16.5 Hz), 7.33 (ddd, 1H, J = 7.6, 7.4, 0.8 Hz), 7.51–7.57 (m, 1H), 7.61 (d, 1H, J = 8.5 Hz), 7.81 (ddd, 1H, J = 8.4, 7.4, 1.7 Hz), 7.96 (dd, 1H, J = 7.7, 1.6 Hz), 8.09-8.13 (m, 2H), 8.56–8.60 (m, 1H), 8.83 (s, 1H), 8.99 (s, 1H), 13.19 (br, 1H); 13C NMR (126 MHz, DMSO-d6) δ 23.6 (CH3), 38.8 (N-1–CH2), 74.2 (C-3), 113.7 (C-3D) 116.6 (C-8), 119.4 (C-4a), 120.7 (C-5C), 123.9 (C-6), 124.5 (C-5D), 128.0 (C-5), 130.6 (C-5A), 137.1 (C-7), 139.7 (C-4A), 140.2 (C-4D), 141.2 (C-8a), 143.2 (C-4C), 148.4 (C-2D), 149.0 (C-6D), 161.7 (COOH), 168.5 (C-2), 189.8 (C-4); 15N NMR (51 MHz, DMSO-d6) 1 δ 249.2 (N-1A), 260.3 (N-1C), 284.1 (N-1D); IR (cm–1): ν 3147, 2926, 1717, 1680, 1600, 1471, 1385, 1278, 1223, 1038, 1000, 781, 755, 663; HRMS (ESI+): m/z calcd for C21H17N8O4+ [M + H]+ 445.1367, found 445.1372. 1-(1-((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)-1,2,3,4- tetrahydro-2,4-dioxo-3-phenylquinolin-3-yl)-1H-1,2,3- triazole-4-carboxylic acid (12d). Colorless solid, mp 139– 162  °C; Rf  =  0.12–0.46 (10% ethanol in chloroform); Rf = 0.00–0.18 (3% ethanol in chloroform); 1H NMR (500 MHz, DMSO-d6) δ 5.11 (d, 1H, J = 15.9 Hz, N-1–CHα), 5.61 (d, 1H, J = 15.9 Hz, N-1–CHβ), 5.61 (d, 2H, J = 14.8 Hz, N-1C–CH2), 7.13–7.20 (m, 2H, H-2B, H-6B), 7.21–7.29 (m, 3H, H-6, H-3B, H-5B), 7.29–7.44 (m, 6H, H-2D, H-6D, H-4D, H-3D, H-5D, H-4B), 7.66 (d, 1H, J = 8.2 Hz, H-8), 7.71 (dd, 1H, J = 8.0, 7.9 Hz, H-7), 7.90 (d, 1H, J = 7.4 Hz, H-5), 8.24 (s, 1H, H-5C), 8.76 (s, 1H, H-5A), 13.25 (br, 1H, COOH); 13C NMR (126 MHz, DMSO-d6) δ 39.8 (N-1– CH2), 52.8 (N-1C–CH2), 80.5 (C-3), 116.6 (C-8), 121.1 (C-4a), 124.0 (C-6), 124.3 (C-5C), 127.7 (C-5), 128.0 (C-2D, C-6D), 128.2 (C-4D), 128.7 (C-2B, C-6B), 128.8 (C-3D, C-5D), 129.3 (C-3B, C-5B), 129.6 (C-1B), 130.5 (C-4B), 131.2 (C-5A), 136.0 (C-1D), 136.6 (C-7), 139.3 (C-4A), 140.8 (C-8a), 141.9 (C-4C), 161.7 (COOH), 166.1 (C-2), 187.9 (C-4); 15N NMR (51 MHz, DMSO-d6) δ 249.8 (N-1A), 250.9 (N-1C), 351.6 (N-3C), 356.4 (N-3A), 362.7 (N-2C); IR (cm–1): ν 3467, 3141, 1717, 1680, 1601, 1469, 1376, 1224, 1038, 872, 760, 724, 696, 665, 610; HRMS (ESI+): m/z calcd for C28H22N7O4+ [M + H]+ 520.1728, found 520.1730. 1-(1,2,3,4-Tetrahydro-2,4-dioxo-3-phenyl-1-((1-phenyl- 1H-1,2,3-triazol-4-yl)methyl)quinolin-3-yl)-1H-1,2,3- triazole-4-carboxylic acid (12e). Colorless solid, mp 153– 169 °C; Rf  =  0.00–0.22 (10% ethanol in chloroform); 1H NMR (500 MHz, DMSO-d6) δ 5.28 (d, 1H, J = 16.0 Hz, N-1–CHα), 5.70 (d, 1H, J = 16.0 Hz, N-1–CHβ), 7.26 (dd, 1H, J = 7.4, 7.3 Hz, H-6), 7.28–7.34 (m, 2H, H-2B, H-6B), 7.35–7.41 (m, 2H, H-3B, H-5B), 7.41–7.46 (m, 1H, H-4B), 433Acta Chim. Slov. 2020, 67, 421–434 Milićević et al.: Preparation of Quinoline-2,4-dione Functionalized ... 7.48–7.54 (m, 1H, H-4D), 7.57-7.65 (m, 2H, H-3D, H-5D), 7.68 (d, 1H, J = 8.3 Hz, H-8), 7.73 (dd, 1H, J = 7.6, 7.4 Hz, H-7), 7.85–7.91 (m, 2H, H2D, H-6D), 7.93 (d, 1H, J = 7.4 Hz, H-5), 8.79 (s, 1H, H-5A), 8.81 (s, 1H, H-5C), 13.12 (br, 1H, COOH); 13C NMR (126 MHz, DMSO-d6) δ 39.2 (N-1–CH2), 80.7 (C-3), 116.7 (C-8), 120.2 (C-2D, C-6D), 121.1 (C-4a), 122.4 (C-5C), 124.1 (C-6), 127.8 (C-5), 128.9 (C-4D), 129.0 (C-2B, C-6B), 129.4 (C-3B, C-5B), 129.7 (C-1B), 130.0 (C-3D, C-5D), 130.7 (C-4B), 131.3 (C-5A), 136.5 (C-1D), 136.8 (C-7), 139.3 (C-4A), 140.7 (C-8a), 142.9 (C-4C), 161.8 (COOH), 166.3 (C-2), 188.0 (C-4); 15N NMR (51 MHz, DMSO-d6) δ 139.5 (N-1), 249.8 (N-1A), 255.6 (N-1C), 354.2 (N-3C), 357.5 (N-3A), 372.6 (N-2A); IR (cm–1): ν 3525, 3145, 3067, 1717, 1681, 1600, 1469, 1377, 1234, 1041, 872, 759, 692, 665; HRMS (ESI+): m/z calcd for C27H20N7O4+ [M + H]+ 506.1571, found 506.1567. 1-(1,2,3,4-Tetrahydro-2,4-dioxo-3-phenyl-1-((1-(pyri- din-2-yl)-1H-1,2,3-triazol-4-yl)methyl)quinolin-3-yl)- 1H-1,2,3-triazole-4-carboxylic acid (12f). Colorless sol- id, mp 116–172 °C; Rf = 0.06 (10% ethanol in chloroform), Rf = 0.00 (5% ethanol in chloroform); 1H NMR (500 MHz, DMSO-d6) δ 5.43 (d, 1H, J = 16.2 Hz, N-1–CHα), 5.64 (d, 1H, J = 16.2 Hz, N-1–CHβ), 7.25 (dd, 1H, J = 7.4, 7.3 Hz, H-6), 7.28–7.36 (m, 2H, H-2B, H-6B), 7.38–7.48 (m, 3H, H-3B, H-4B, H-5B), 7.50–7.59 (m, 2H, H-8, H-5D), 7.69 (dd, 1H, J = 7.6, 7.5 Hz, H-7), 7.95 (d, 1H, J = 7.4 Hz, H-5), 8.07-8.19 (m, 2H, H-3D, H-4D), 8.56–8.64 (m, 1H, H-6D), 8.79-8.91 (m, 2H, H-5C, H-5A), 13.23 (br, 1H, COOH); 13C NMR (126 MHz, DMSO-d6) δ 39.7 (N-1–CH2), 80.8 (C-3), 113.7 (C-3D), 116.5 (C-8), 120.9 (C-5C), 121.2 (C-4a), 124.0 (C-6), 124.5 (C-5D), 127.9 (C-5), 128.9 (C-2B, C-6B), 129.5 (C-3B, C-5B), 129.8 (C-1B), 130.7 (C-4B), 131.3 (C-5A), 136.7 (C-7), 139.2 (C-4A), 140.3 (C-4D), 140.4 (C-8a), 143.0 (C-4C), 148.3 (C-2D), 149.0 (C-6D), 161.8 (COOH), 166.7 (C-2), 187.9 (C-4); 15N NMR (51 MHz, DMSO-d6) δ 137.8 (N-1), 249.7 (N-1A), 260.4 (N-1C), 284.9 (N-1D), 356.8 (N-3A), 357.1 (N-3C); IR (cm–1): ν 3435, 3157, 2927, 1718, 1682, 1600, 1470, 1375, 1313, 1189, 1035, 779, 758, 696; HRMS (ESI+): m/z calcd for C26H19N8O4+ [M + H]+ 507.1524, found 507.1527. Acknowledgments. This work was financed by TBU in Zlín (internal grant no. IGA/FT/2019/010, funded from the resources of specific university research). The authors acknowledge also the financial support from the Slovenian Research Agency (Research Core Funding Grant P1-0230, Project J1-8147, and Project J1-9166). 5. References 1. D. Urankar, B. Pinter, A. Pevec, F. De Proft, I. Turel, J. Košmrlj, Inorg. Chem. 2010, 49, 4820–4829. DOI:10.1021/ic902354e 2. K. J. Kilpin, E. L. Gavey, C. J. McAdam, C. B. Anderson, S. J. Lind, C. C. Keep, K. C. Gordon, J. D. Crowley, Inorg Chem 2011, 50, 6334–6346. DOI:10.1021/ic200789b 3. J. D. Crowley, D. A. McMorran, Top. Heterocycl. Chem. 2012, 28, 31–84. DOI:10.1007/7081_2011_67 4. R. J. Detz, S. A. Heras, R. de Gelder, P. W. N. M. Van Leeuwen, H. Hiemstra, J. N. H. Reek, J. H. Van Maarseveen, Org. Lett. 2006, 8, 3227–3230. DOI:10.1021/ol061015q 5. B. Beyer, C. Ulbricht, D. Escudero, C. Friebe, A. Winter, L. González, U. S. Schubert, Organometallics 2009, 28, 5478– 5498. DOI:10.1021/om9003785 6. A. Kumar, R. K. Chhatra, P. S. Pandey, Org. Lett. 2010, 12, 24–27. DOI:10.1021/ol902351g 7. S. H. Kim, H. S. Choi, J. Kim, S. J. Lee, D. T. Quang, J. S. Kim, Org. Lett. 2010, 12, 560–563. DOI:10.1021/ol902743s 8. J. M. Fernández-Hernández, C. H. Yang, J. I. Beltrán, V. Lemaur, F. Polo, R. Fröhlich, J. Cornil, L. De Cola, J. Am. Chem. Soc. 2011, 133, 10543–10558. DOI:10.1021/ja201691b 9. Y. C. Duan, Y. C. Ma, E. Zhang, X. J. Shi, M. M. Wang, X. W. Ye, H. M. Liu, Eur. J. Med. Chem. 2013, 62, 11–19. DOI:10.1016/j.ejmech.2012.12.046 10. B. Garudachari, A. M. Isloor, M. N. Satyanarayana, H.- K. Fun, G. Hegde, Eur. J. Med. Chem. 2014, 74, 324–332. DOI:10.1016/j.ejmech.2014.01.008 11. Y. W. He, C. Z. Dong, J. Y. Zhao, L. L. Ma, Y. H. Li, H. A. Aisa, Eur. J. Med. Chem. 2014, 76, 245–255. DOI:10.1016/j.ejmech.2014.02.029 12. K. T. Petrova, T. M. Potewar, P. Correira-da-Silva, M. T. Bar- ros, R. C. Calhelha, A. Ćiric, M. Soković, I. C. F. R. Ferreira, Carbohydr. Res. 2015, 417, 66–71. DOI:10.1016/j.carres.2015.09.003 13. I. Fichtali, W. Laaboudi, E. M. El Hadrami, F. El Aroussi, A. Ben-Tama, M. Benlemlih, S. E. Stiriba, J. Mater. Environ. Sci. 2016, 7, 1633–1641. 14. M. R. Jones, E. Mathieu, C. Dyrager, S. Faissner, Z. Vaillan- court, K. J. Korshavn, M. H. Lim, A. Ramamoorthy, V. W. Yong, S. Tsutsui, P. K. Stys, T. Storr, Chem. Sci. 2017, 8, 5636– 5643. DOI:10.1039/C7SC01269A 15. A. Bolje, J. Košmrlj, Org. Lett. 2013, 15, 5084–5087. DOI:10.1021/ol4024584 16. A. Bolje, S. Hohloch, D. Urankar, A. Pevec, M. Gazvoda, B. Sarkar, J. Košmrlj, Organometallics 2014, 33, 2588–2598. DOI:10.1021/om500287t 17. S. Hohloch, S. Kaiser, F. L. Duecker, A. Bolje, R. Maity, J. Košmrlj, B. Sarkar, Dalton Trans. 2015, 44, 686–693. DOI:10.1039/C4DT02879A 18. M. Gazvoda, M. Virant, A. Pevec, D. Urankar, A. Bolje, M. Kočevar, J. Košmrlj, Chem. Commun. (Cambridge, U. K.) 2016, 52, 1571–1574. DOI:10.1039/C5CC08717A 19. K. Proisl, S. Kafka, J. Košmrlj, Curr. Org. Chem. 2017, 21, 1949–1975. DOI:10.2174/1385272821666170711155631 20. S. Kafka, S. Hauke, A. Salčinović, O. Soidinsalo, D. Urankar, J. Košmrlj, Molecules 2011, 16, 4070–4081. DOI:10.3390/molecules16054070 21. A. C.-M. Daugan, Y. Lamotte, O. Mirguet, Quinolinone de- 434 Acta Chim. Slov. 2020, 67, 421–434 Milićević et al.: Preparation of Quinoline-2,4-dione Functionalized ... rivatives, PCT Int Appl WO 2012/119978, date of patent Sep- tember 13, 2012. 22. N. P. Grimster, B. Stump, J. R. Fotsing, T. Weide, T. T. Talley, J. G. Yamauchi, A. Nemecz, C. Kim, K.-Y. Ho, K. B. Sharpless, P. Taylor, V. V. Fokin, J. Am. Chem. Soc. 2012, 134, 6732–6740. DOI:10.1021/ja3001858 23. J. G. Yamauchi, K. Gomez, N. Grimster, M. Dufouil, A. Nemecz, J. R. Fotsing, K.-Y. Ho, T. T. Talley, K. B. Sharpless, V. V. Fokin, P. Taylor, Mol. Pharmacol. 2012, 82, 687–699. DOI:10.1124/mol.112.080291 24. C. D. Rillahan, E. Schwartz, R. McBride, V. V. Fokin, J. C. Paulson, Angew. Chem. Int. Ed. 2012, 51, 11014–11018. DOI:10.1002/anie.201205831 25. Y. Miyamoto, J. Kalisiak, K. Korthals, T. Lauwaet, D. Y. Che- ung, R. Lozano, E. R. Cobo, P. Upcroft, J. A. Upcroft, D. E. Berg, F. D. Gillin, V. V. Fokin, K. B. Sharpless, L. Eckmann, Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 17564–17569. DOI:10.1073/pnas.1302664110 26. J. S. Oakdale, R. K. Sit, V. V. Fokin, Chem. – Eur. J. 2014, 20, 11101–11110. DOI:10.1002/chem.201402559 27. V. Fokin, B. K. Sharpless, L. Eckmann, Y. Miyamoto, Expanded therapeutic potential in nitroheteroaryl antimicrobials, PCT Int Appl WO 2014/205414, date of patent December 24, 2014. 28. J. Dong, K. B. Sharpless, Sulfur(VI) fluoride compounds and methods for the preparation thereof, PCT Int Appl WO 2015/188120, date of patent December 10, 2015. 29. W. J. Kim, K. A. Korthals, S. Li, C. Le, J. Kalisiak, K. B. Shar- pless, V. V. Fokin, Y. Miyamoto, L. Eckmann, Antimicrob. Agents Chemother. 2017, 61, e02397/1– e02397/12. DOI:10.1128/AAC.02397-16. 30. D. Milićević, R. Kimmel, M. Gazvoda, D. Urankar, S. Kafka, J. Košmrlj, Molecules 2018, 23, 2310/1–2310/21. DOI:10.3390/molecules23092310 31. N. Boechat, V. F. Ferreira, S. B. Ferreira, M. de L. G. Ferreira, Da F. de C. Silva, M. M. Bastos, M. dos S. Costa, M. C. S. Lourenço, A. C. Pinto, A. U. Krettli, A. C. Aguiar, B. M. Teix- eira, Da N. V. Silva, P. R. C. Martins, F. A. F. M. Bezerra, A. L. S. Camilo, G. P. Da Silva, C. C. P. Costa, J. Med. Chem. 2011, 54, 5988–5999. DOI:10.1021/jm2003624 32. D. M. Reddy, J. Srinivas, G. Chashoo, A. K. Saxena, H. M. S. Kumar, Eur. J. Med. Chem. 2011, 46, 1983–1991. DOI:10.1016/j.ejmech.2011.02.016 33. M. Aufort, J. Herscovici, P. Bouhours, N. Moreau, C. Girard, Bioorg. Med. Chem. Lett. 2008, 18, 1195–1198. DOI:10.1016/j.bmcl.2007.11.111 34. P. R. Bagdi, R. S. Basha, A. T. Khan, RSC Adv. 2015, 5, 61337– 61344. DOI:10.1039/C5RA09671E 35. B. Orzeszko, M. Fedoryński, A. E. Laudy, B. J. Starościak, A. Orzeszko, Acta Pol. Pharm. 2006, 63, 374–377. 36. T. Sasaki, S. Eguchi, M. Yamaguchi, T. Esaki, J. Org. Chem. 1981, 46, 1800–1804. DOI:10.1021/jo00322a009 37. X. Wang, Z.-C. Dai, Y.-F. Chen, L.-L. Cao, W. Yan, S.-K. Li, J.- X. Wang, Z.-G. Zhang, Y.-H. Ye, Eur. J. Med. Chem. 2017, 126, 171–182. DOI:10.1016/j.ejmech.2016.10.006 38. C. Han, S. Dong, W. Zhang, Z. Chen, Synlett 2018, 29, 673– 677. DOI:10.1055/s-0036-1589157 39. M. N. Rajadhyaksha, R. Nair, P. V. Ramesan, K. Johnson, A. M. Panandikar, Process for preparation of fluorinated triazole compound, PCT Int Appl WO 2012/032540, date of patent March 15, 2012. 40. Y. Naro, N. Ankenbruck, M. Thomas, Y. Tivon, C. M. Connel- ly, L. Gardner, A. Deiters, J. Med. Chem. 2018, 61, 5900–5909. DOI:10.1021/acs.jmedchem.7b01891 41. J. M. Rieger, M. L. Brown, G. W. Sullivan, J. Linden, T. L. Mac- donald, J. Med. Chem. 2001, 44, 531–539. DOI:10.1021/jm0003642 42. G. Abbiati, A. Contini, D. Nava, E. Rossi, Tetrahedron 2009, 65, 4664–4670. DOI:10.1016/j.tet.2009.04.041 43. D.-S. Kim, K. Bolla, S. Lee, J. Ham, Tetrahedron 2011, 67, 1062–1070. DOI:10.1016/j.tet.2010.12.049 44. Oxford Diffraction, CrysAlis PRO, Oxford Diffraction Ltd., Yarnton, England, 2009. 45. G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr. 2008, 64, 112–122. DOI:10.1107/S0108767307043930 46. G. M. Sheldrick, Acta Crystallogr., Sect. C: Struct. Chem. 2015, 71, 3–8. DOI:10.1107/S2053229614024218 Povzetek V prispevku je opisana kisla etanoliza (deacetiliranje) (1-(2,4-diokso-1,2,3,4-tetrahidrokinolin-3-il)-1H-1,2,3-tri- azol-4-il)metil acetatov, substituiranih na dušikovem atomu kinolindionske skupine s propargilno skupino ali pa z (1-substituirano 1H-1,2,3-triazol-4-il)metilno skupino. Izhodni acetate so pripravili iz ustreznih 3-(4-hidroksime- til-1H-1,2,3-triazol-1-il)kinolin-2,4(1H, 3H)-dionov, ki niso substituirani na kinolonskem dušiku, po še opisanih post- opkih. Tako dobljene primarne alkohole, kot tudi tiste, ki niso substituirani na kinolonskem dušiku, so oksidirali bodisi v aldehide s piridinijevim klorokromatom (PCC), ali pa z manganovim dioksidom v karboksilne kisline, ob uporabi Jones-ovega reagent v acetonu kot topilu. Strukture vseh pripravljenih spojin so potrdili z 1H, 13C and 15N NMR spec- troskopijo. Ustrezne rešitve struktur analiziranih spojin so bile narejene na podlagi standardnih 1D in izbranih gradi- entnih 2D NMR poskusov (1H–1H gs-COSY, 1H–13C gs-HSQC, 1H–13C gs-HMBC), skupaj z 1H–15N gs-HMBC, kot praktičnim orodjem za določitev 15N NMR kemijskih premikov v spojinah, ki niso obogatene z 15N izotopom. Except when otherwise noted, articles in this journal are published under the terms and conditions of the  Creative Commons Attribution 4.0 International License