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Article

Copper(I)-Catalyzed [ 3+ 2] Cycloaddition of 3-Azidoquinoline-2,4(1H,3H)-diones with Terminal Alkynes †

1
Department of Chemistry, Faculty of Technology, Tomas Bata University in Zlin, Zlin 76272, Czech Republic
2
Institute of Chemistry, University of Potsdam, Golm D-14476, Germany
3
Faculty of Natural Sciences and Mathematics, University of Banja Luka, Banja Luka 78000, Bosnia and Herzegovina
4
Department of Chemistry, Faculty of Science, University of Helsinki, Helsinki FI-00014, Finland
5
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana SI-1000, Slovenia
*
Authors to whom correspondence should be addressed.
Dedicated to Professor Antonín Klásek on the occasion of his 70th birthday.
Molecules 2011, 16(5), 4070-4081; https://doi.org/10.3390/molecules16054070
Submission received: 18 April 2011 / Revised: 11 May 2011 / Accepted: 13 May 2011 / Published: 18 May 2011
(This article belongs to the Section Organic Chemistry)

Abstract

:
3-Azidoquinoline-2,4(1H,3H)-diones 1, which are readily available from 4-hydroxyquinolin-2(1H)-ones 4 via 3-chloroquinoline-2,4(1H,3H)-diones 5, afford, in copper(I)-catalyzed [3 + 2] cycloaddition reaction with terminal acetylenes, 1,4-disubstituted 1,2,3-triazoles 3 in moderate to excellent yields. The structures of compounds 3 were confirmed by 1H and 13C-NMR spectroscopy, combustion analyses and mass spectrometry.

Graphical Abstract

1. Introduction

As a part of our continuous interest in quinolinedione chemistry, we observed that 3-azidoquinoline-2,4(1H,3H)-diones 1 behave quite differently than normally expected for organic azides, including α-azido carbonyl compounds [1]. For example, the Staudinger reaction [2], the reduction of azide with triphenylphosphine, did not yield the expected 3-aminoquinoline-2,4(1H,3H)-diones (Scheme 1) and instead, deazidation took place to afford 4-hydroxyquinolin-2(1H)-ones. Similar behaviour of 3-azidoquinoline-2,4(1H,3H)-diones was also observed in the reaction with zinc in acetic acid [1].
Scheme 1. Previously documented unexpected reactivity of 3-azidoquinoline-2,4(1H,3H)-diones 1.
Scheme 1. Previously documented unexpected reactivity of 3-azidoquinoline-2,4(1H,3H)-diones 1.
Molecules 16 04070 g002
This unexpected reactivity prompted us to continue the studies of 3-azidoquinoline-2,4(1H,3H)-diones reactivity. For examples, we were intrigued whether these compounds could serve as partners in copper(I)-catalyzed [3 + 2] cycloaddition reaction with terminal alkynes. This reaction, also referred to as “Click reaction”, has been recently discovered to selectively afford 1,4-disubstituted 1,2,3-triazoles [3,4,5]. Its remarkably mild reaction conditions, broad scope, and exquisite selectivity are well documented, and it has succeeded in the presence of most functional groups tested to date. It has also become a powerful and versatile tool in nearly all areas of chemistry, including macromolecular engineering, nanotechnology, and drug discovery [6,7,8,9,10].

2. Results and Discussion

Starting 3-azidoquinoline-2,4(1H,3H)-diones 1 were prepared by known chemistry from the corresponding 4-hydroxyquinolin-2-(1H)-ones 4. Chlorination and bromination of the latter with sulfuryl chloride and bromine, respectively, afforded the corresponding 3-chloroquinoline-2,4(1H,3H)-diones 5 and 3-bromoquinoline-2,4(1H,3H)-diones 6. The resulting 3-halogenoquinoline-2,4(1H,3H)-diones were subsequently subjected to the substitution with sodium azide.
3-Azidoquinoline-2,4(1H,3H)-diones 1 were examined as partners in copper(I) catalyzed [3 + 2] cycloaddition (Scheme 2). Three different terminal acetylenes 2 were chosen; phenylacetylene (2a), propargyl alcohol (2b) and 3-ethynylaniline (2c). When screening for the optimal reaction conditions, we initially tested the most commonly used system, copper(II) sulphate pentahydrate and ascorbic acid as a source of copper(I) in tert-BuOH/H2O as a solvent [6]. Interestingly, no reaction could be detected by thin-layer chromatography (TLC) analysis after 24 h and the starting azides 1 were recovered nearly quantitatively from the reaction mixtures. Similarly unsuccessful were attempts to use a combination of copper(II) acetate and elemental copper in acetonitrile. We assumed that the prime reasons for the failure of these reactions were the extremely low solubilities of azides 1 in the reaction media used. Similar difficulties were previously encountered by some of us in attempts at using sparingly soluble propargyl functionalized diazenecarboxamides [11] or azido-appended platinum(II) complexes [12] as click components. In those instances the use of dimethyl sulfoxide (DMSO) as a reaction solvent and a combination of copper(II) sulphate pentahydrate and elemental copper (CuSO4/Cu(0)) provided results that were superior to other combinations. Conducting the cycloadditions between azides 1 and acetylenes 2 in DMSO, in the presence of CuSO4/Cu(0) couple afforded the expected 1,4-disubstituted 1,2,3-triazoles 3 in moderate to excellent yields, as shown in Table 1.
Scheme 2. Copper(I) catalyzed cycloaddition between 3-azidoquinoline-2,4(1H,3H)-diones 1 and terminal acetylenes into 1,2,3-triazoles 3.
Scheme 2. Copper(I) catalyzed cycloaddition between 3-azidoquinoline-2,4(1H,3H)-diones 1 and terminal acetylenes into 1,2,3-triazoles 3.
Molecules 16 04070 g003
Table 1. Reaction conditions and yields for the formation of 1,2,3-triazoles 3 (Scheme 2) a.
Table 1. Reaction conditions and yields for the formation of 1,2,3-triazoles 3 (Scheme 2) a.
EntryAzideAlkyneTriazoleR. time, hYield, % b
1R1R2R3R42R53
11AHPhHH2aPh3Aa3.396 (80)
21AHPhHH2bCH2OH3Ab1.595 (67)
31AHPhHH2c3-(NH2)-C6H43Ac1.3nd (61)
41BHPhMeOH2aPh3Ba2.298 (64)
51BHPhMeOH2bCH2OH3Bb1.185 (nd)
61CHPrMeOH2aPh3Ca1.297 (78)
71CHPrMeOH2bCH2OH3Cb3nd (60)
81DHPhClMeO2aPh3Da1.292 (82)
91DHPhClMeO2bCH2OH3Db3nd (46)
101EBnPhHH2aPh3Ea2.597 (51)
111EBnPhHH2bCH2OH3Eb294 (89)
a Reaction conditions: 1 (2.00 mmol), 2 (2.02 mmol), CuSO4∙5H2O (0.2 mmol, 10 mol %), granular copper (8.8 mmol), DMSO (6 mL), air, room temperature, darkness; b Chemical yield of NMR pure, crude isolated product. The value in parentheses refers to the yield of crystallized product; nd: not determined.
In a general procedure, a mixture of 3-azidoquinoline-2,4(1H,3H)-dione (1, 2.0 mmol), terminal alkyne (2, 2.0 mmol), CuSO4∙5H2O (0.2 mmol, 10 mol %), and granular copper (8.8 mmol) in DMSO (6 mL) was stirred at room temperature, in the presence of air. Since azides 1 are prone to slow decomposition in the presence of light, we decided to perform the reactions in darkness. The cycloadditions were completed within a few hours (Table 1), and as judged by TLC analyses, the corresponding 1,4-disubstituted 1,2,3-triazoles 3 were formed quantitatively. In most cases the products were isolated by simple extractive workup in excellent chemical yields and more than 95% purity as judged by 1H-NMR and TLC analyses (Table 1, entries 1, 2, 4–6, 8, 10 and 11). The relatively high loads of granular copper could easily be recovered and eventually reused.
The structures of triazoles 3 were confirmed by 1H- and 13C-NMR spectroscopy, combustion analyses and mass spectrometry on the crystallized compounds. In one instance, that of 3Cb, the expected 1,4-regiochemistry at the 1,2,3-triazole ring was confirmed by a NOESY experiment. As demonstrated in Figure 1, the triazole hydrogen atom (Htriazole) displays five NOE cross peaks; three to the propyl group bound to C3 of the quinolinedione core and two to the hydroxymethyl group, attached to C4’ of the triazole ring. The most important for the assigned regiochemistry is the cross peak of Htriazole to the C3-CH2 protons, which would not be possible for the isomeric 1,5-disubstituted product. The absence of a cross peak between the hydroxymethyl group and C3-CH2 further corroborates the structure of 3Cb.
Figure 1. Expansions of NOESY spectrum and chemical drawing of compound 3Cb showing relevant NOE cross peaks.
Figure 1. Expansions of NOESY spectrum and chemical drawing of compound 3Cb showing relevant NOE cross peaks.
Molecules 16 04070 g001
In one instance, that of 3-phenyl-3-(4-phenyl-1H-1,2,3-triazol-1-yl)quinoline-2,4(1H,3H)-dione(3Aa), the preparation of 3-azido-3-phenylsquinoline-2,4(1H,3H)-dione (1A) and its cycloaddition with phenylacetylene were conducted as a one-pot multicomponent reaction, i.e., by mixing the corresponding 3-bromoquinolinedione substrate 6A, sodium azide and alkyne (2a) in the presence of Cu(II)/Cu(0) (Experimental section). Similar one-pot azidation-cycloaddition procedures are described in the literature [13,14] This protocol afforded the desired product (3Aa) in modest 43% yield. 3-(4-(3-Aminophenyl)-1H-1,2,3-triazol-1-yl)-3-phenylquinoline-2,4(1H,3H)-dione (3Ac) was acetylated into N-(3-(1-(1,2,3,4-tetrahydro-2,4-dioxo-3-phenylquinolin-3-yl)-1H-1,2,3-triazol-4-yl)phenyl)-acetamide (3Ae). Whereas α-azido-β-carbonyl lactam has previously been used as a reaction partner [15], to the best our knowledge, this is not the case with 3-azidoquinoline-2,4(1H,3H)-diones.

3. Experimental

3.1. General

Reagents and solvents were commercially sourced (Fluka, Aldrich, Alfa Aesar) and used as purchased. Granular copper (particle size 0.2–0.7 mm), coating quality (99.9%, Fluka #61144) was used. For column chromatography, Fluka Silica gel 60, 220–440 mesh was used. The course of separation and also the purity of substances were monitored by TLC on Alugram® SIL G/UV254 foils (Macherey-Nagel). NMR spectra were recorded at 302 K on a Bruker Avance DPX 300 spectrometer operating at 300 MHz (1H) and 75 MHz (13C), and Bruker Avance III 500 MHz NMR instrument operating at 500 MHz (1H) and 125 MHz (13C). Proton spectra were referenced to TMS as internal standard. Carbon chemical shifts were determined relative to the 13C signal of DMSO-d6 (39.5 ppm). 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). Phase sensitive NOESY with gradient pulses in mixing time, of 3Cb, was recorded in DMSO-d6(c = 21 mM) using standard pulse sequence from the Bruker pulse library (noesygpphpp in the Bruker software) at 296 K, with mixing time of 300 ms and relaxation delay of 2 s. Mass spectra and high-resolution mass spectra were obtained with a VG-Analytical AutospecQ instrument and Q-TOF Premier instrument. Data are reported as m/z (relative intensity). The IR spectra were recorded on a Perkin-Elmer 421 and 1310 and Mattson 3000 spectrophotometers using samples in potassium bromide disks. Elemental analyses (C, H, N) were performed with FlashEA1112 Automatic Elemental Analyzer (Thermo Fisher Scientific Inc.). The melting points were determined on a Kofler block or Gallenkamp apparatus and are uncorrected. Starting compounds 1, 4–6 were prepared by known procedures as shown in Scheme 3 and described below.
Scheme 3. Preparation of starting compounds 46. For key to substituents, please see Table 1.
Scheme 3. Preparation of starting compounds 46. For key to substituents, please see Table 1.
Molecules 16 04070 g004
4-Hydroxyquinolin-2-(1H)-ones: 4-Hydroxy-3-phenylquinolin-2(1H)-one (4A) [18], 4-hydroxy-6-methoxy-3-phenylquinolin-2(1H)-one (4B) [19], 6-chloro-4-hydroxy-7-methoxy-3-phenylquinolin-2(1H)-one (4D) [19], and 1-benzyl-4-hydroxy-3-phenylquinolin-2(1H)-one (4E) [1] were prepared by thermal condensation of the appropriate anilines and substituted malonic acids diethyl esters neat, as described in the literature. 1-Benzyl-3-chloro-3-phenylquinoline-2,4(1H,3H)-dione (5E) was prepared by chlorination of compound 4E with sulfuryl chloride according to the literature procedure [1]. 3-Bromo-3-phenylquinoline-2,4(1H,3H)-dione (6A) and 3-bromo-6-methoxy-3-phenylquinoline-2,4-(1H,3H)-dione (6B) were prepared by bromination of compounds 4A and 4B, respectively, as described in the literature [20]. 3-Azido-1-benzyl-3-phenylquinoline-2,4(1H,3H)-dione (1E) was prepared by the reaction of 1-benzyl-3-chloro-3-phenylquinoline-2,4(1H,3H)-dione (5E) with sodium azide as described formerly [1].

3.2. 4-Hydroxy-6-methoxy-3-propylquinolin-2(1H)-one (4C)

A mixture of 4-methoxyaniline (6.16 g, 50 mmol) and diethyl propylmalonate (10.52 g, 52 mmol) was heated on a metal bath at 220–230 °C for 1 h and then at 260–280 °C for 3 h (the reaction was complete when the distillation of ethanol stopped). After cooling, the solid product was crushed, suspended in aqueous sodium hydroxide solution (0.5 M, 125 mL) and after filtration the filtrate was washed with toluene (3 × 20 mL). The aqueous phase was filtered and acidified by concentrated hydrochloric acid. The precipitated crude product was filtered, washed with water, air dried and crystallized from ethanol affording white solid of 4C, yield 5.90 g (51%); mp 238–243 °C; IR (cm−1): 2961, 1644 (CO), 1618, 1607, 1591, 1453, 1272, 1240, 1202, 1164; 1H-NMR (DMSO-d6) 0.91 (t, J = 7.3 Hz, 3H), 1.39–1.51 (m, 2H), 2.50–2.56 (m, 2H), 3.79 (s, 3H), 7.08 (dd, J = 9.0, 2.7 Hz, 1H), 7.19 (d, J = 9.1 Hz, 1H), 7.36 (d, J = 2.6 Hz, 1H), 9.89 (s, 1H), 11.14 (s, 1H); 13C-NMR (DMSO-d6) 13.9, 21.3, 25.0, 55.4, 104.2, 111.9, 115.7, 116.1, 118.6, 131.8, 153.7, 156.5, 163.0; MS (EI) m/z (%): 233 ([M]+, 97), 218 (92), 205 (97), 204 (100), 191 (37); Anal. Calcd for C13H15NO3 (233.26): C, 66.94; H, 6.48; N, 6.00; Found: C, 67.07; H, 6.55; N, 6.21.

3.3. 3-Chloro-6-methoxy-3-propylquinoline-2,4(1H,3H)-dione (5C)

To a stirred suspension of 4-hydroxy-6-methoxy-3-propylquinolin-2(1H)-one (4C, 3.97 g, 17 mmol) in dioxane (50 mL) preheated to 50 °C, sulfuryl chloride (7.8 g, 57 mmol) was added dropwise, keeping the temperature below 55 °C. The resulting reaction mixture was stirred for additional 10 min at 50–55 °C, cooled down to room temperature and poured into ice-water (850 mL). The precipitated crude product was filtered, washed with water (200 mL), air dried and crystallized from benzene affording bright yellow solid of 5C, yield 3.48 g (76%); mp 138–142 °C; IR (cm−1): 2918, 1703 (CO), 1672 (CO), 1504, 1430, 1288, 1203; 1H-NMR (DMSO-d6) 0.86 (t, J = 7.2 Hz), 1.12–1.30 (m, 2H), 2.20–2.29 (m, 2H), 3.80 (s, 3H), 7.11 (d, J = 8.7 Hz, 1H), 7.30 (dd, J = 7.2, 3.0 Hz, 1H), 7.34 (d, J = 3.0 Hz, 1H), 11.16 (s, 1H); 13C-NMR (DMSO-d6) 13.8, 17.9, 37.9, 55.6, 66.7, 109.0, 117.6, 118.3, 125.3, 135.1, 155.1, 166.3, 188.4; MS (EI) m/z (%): 269 ([M{37Cl}]+, 17), 267 ([M{35Cl}]+, 42), 240 (48), 238 (100), 233 (33), 225 (52); Anal. Calcd for C13H14ClNO3 (267.71): C, 58.32; H, 5.27; N, 5.23. Found: C, 58.58; H, 5.07; N, 5.36.

3.4. Chlorination of 6-chloro-4-hydroxy-7-methoxy-3-phenylquinolin-2(1H)-one (4D) into 3,6-Dichloro-7-methoxy-3-phenylquinoline-2,4(1H,3H)-dione (5D) and 3,6,8-Trichloro-7-methoxy-3-phenylquinoline-2,4(1H,3H)-dione (5F)

Sulfuryl chloride (16.7 g; 124 mmol) was added dropwise to the stirred suspension of 6-chloro-4-hydroxy-7-methoxy-3-phenylquinolin-2(1H)-one (4D, 10.00 g; 37.41 mmol) in dioxane at 46–47 °C during 20 min. The resulting reaction mixture was stirred for 10 min and poured into ice-water (600 mL). The precipitated solid was filtered, washed with water, dried on the air and crystallized from benzene (1.3 L) affording compound 5D. The mother liquor was concentrated in vacuo to approximately 380 mL. The precipitated solid was filtered and recrystallized from benzene to give compound 5F.
3,6-Dichloro-7-methoxy-3-phenylquinoline-2,4(1H,3H)-dione (5D): White solid, yield 6.33 g (50%); mp 236–238 °C (236 °C from acetic acid [20]); IR (cm−1): 1710 (CO), 1679 (CO), 1614, 1595, 1485, 1445, 1400, 1335; 1H-NMR (DMSO-d6) 3.93 (s, 3H, CH3), 6.84 (s, 1H), 7.29–7.38 (m, 5H), 7.66 (s, 1H), 11.13 (s, 1H); 13C-NMR (DMSO-d6) 56.8, 74.4, 100.0, 111.4, 116.7, 127.0, 128.5, 128.8, 129.3, 134.9, 141.9, 160.6, 166.6, 185.5; MS (EI) m/z (%): 339 ([M{37Cl2}]+, 6), 337 ([M{37Cl35Cl}]+, 31), 335 ([M{35Cl2}]+, 42), 303 (45), 302 (54), 301 (100), 300 (83), 186 (28), 184 (67), 183 (32); Anal. Calcd for C16H11Cl2NO3 (336,17): C, 57.16; H, 3.30; N, 4.17. Found: C, 57.16; H, 3.26; N, 4.10.
3,6,8-Trichloro-7-methoxy-3-phenylquinoline-2,4(1H,3H)-dione (5F): White solid, yield 0.82 g (6%); mp 183–186 °C (198 °C from pet. ether [20]); IR (cm−1): 3238 (NH), 1728 (CO), 1696 (CO), 1596, 1463, 1317, 1055, 966, 749, 692; MS (EI) m/z (%): 373 ([M{37Cl235Cl}]+, 4), 371 ([M{37Cl35Cl2}]+, 11), 369 ([M{35Cl3}]+, 11), 338 (20), 337 (63), 336 (78), 335 (99), 334 (100), 220 (27), 218 (41), 89 (27). Anal. Calcd for C16H10Cl3NO3 (370.61): C, 51.85; H, 2.72; N, 3.78. Found: C, 51.92; H, 2.70; N, 3.61.

3.5. General Procedure for the Synthesis 3-Azidoquinoline-2,4(1H,3H)-diones 1A–D

To a stirred solution of the appropriate 3-chloro- (5A,B) or 3-bromoquinoline-2,4(1H,3H)-dione (6C,D, 10 mmol) in DMF (50 mL), sodium azide (975 mg, 15 mmol) was added in small portions in darkness during 20 min. The reaction mixture was stirred in darkness for 2 h and then poured into ice-water (600 mL). The precipitated product 1 was filtered, washed with water (150 mL) and dried at 50–60 °C in darkness. Products 1A, 1C, 1D were crystallized from the solvents indicated below.
3-Azido-3-phenylquinoline-2,4(1H,3H)-dione (1A): White solid, yield 2.13 g (77%); mp 173–181 °C (benzene; 170–172 °C [1]).
3-Azido-6-methoxy-3-phenyquinoline-2,4(1H,3H)-dione (1B): Yellow solid, yield 2.76 g (90%); mp 183–185 °C (182–183 °C from ethanol [20]). Anal. Calcd for C16H12N4O3 (308.29): C, 62.33; H, 3.92; N, 18.17. Found: C, 62.21; H, 4.09; N, 18.22.
3-Azido-6-methoxy-3-propylquinoline-2,4(1H,3H)-dione (1C): Yellow solid, yield 2.39 g (87%); mp 170–171 °C (ethanol); IR (cm−1): 2962, 2121 (N3), 1700 (CO), 1665 (CO), 1509, 1492, 1424, 1354, 1208, 826; 1H-NMR (DMSO-d6) 0.81 (t, J = 7.2 Hz, 3H), 1.20–1.32 (m, 2H), 1.80–1.97 (m, 2H), 3.78 (s, 3H), 7.06 (d, J = 8.8 Hz, 1H), 7.21 (d, J = 3.0 Hz, 1H), 7.28 (dd, J = 8.8, 3.0 Hz, 1H), 10.96 (s, 1H); 1H-NMR (CDCl3) 0.91 (t, J = 7.3 Hz, 3H), 1.37–1.49 (m, 2H), 2.04–2.22 (m, 2H), 3.85 (s, 3H), 7.00 (d, J = 8.7 Hz, 1H), 7.19 (dd, J = 8.9, 2.8 Hz, 1H), 7.38 (d, J = 2.8 Hz, 1H), 9.58 (s, 1H); 13C-NMR (DMSO-d6) 13.4, 16.7, 39.2, 55.5, 74.5, 108.7, 118.1, 118.9, 124.5, 135.2, 154.9, 168.5, 191.2; 13C-NMR (CDCl3) 13.7, 17.1, 39.9, 55.8, 73.6, 109.4, 118.1, 119.3, 125.3, 133.9, 156.4, 170.5, 191.6; MS (EI) m/z (%): ([M]+, 30), 218 (28), 149 (100), 121 (39), 106 (66); Anal. Calcd for C13H14N4O3 (274.28): C, 56.93; H, 5.14; N, 20.43. Found: C, 56.72; H, 5.36; N, 20.37.
3-Azido-6-chloro-7-methoxy-3-phenylquinoline-2,4(1H,3H)-dione (1D): White solid, yield 3.14 g (92%); mp 228–232 °C dec. (ethanol); IR (cm−1): 2976, 2920, 2126 (N3), 1710 (CO), 1670 (CO), 1613, 1590, 1407, 1348, 1279; 1H-NMR (DMSO-d6) 3.91 (s, 3H, CH3), 6.73 (s, 1H), 7.35–7.41 (m, 2H), 7.41–7.49 (m, 3H), 7.72 (s, 1H), 11.42 (s, 1H); 13C-NMR (DMSO-d6) 56.7, 76.8, 100.0, 112.3, 116.5, 126.6, 128.1, 129.6, 130.0, 133.3, 141.9, 160.3, 168.1, 187.1; MS (EI) m/z (%): 344 ([M{37Cl}]+, 3), 342 ([M{35Cl}]+, 9), 318 (11), 316 (40), 314 (22), 303 (17), 302 (21), 301 (51), 300 (38), 183 (100); Anal. Calcd for C16H11ClN4O3 (342.74): C, 56.07; H, 3.23; N, 16.35. Found: C, 56.30; H, 3.24; N, 16.45.

3.6. General Procedure for the Preparation of 1,2,3-Triazoles 3

A mixture of 3-azidoquinoline-2,4(1H,3H)-dione (1, 2.00 mmol), terminal alkyne (2, 2.02 mmol), CuSO4×5H2O (0.2 mmol, 10 mol%), granular copper (8.8 mmol), and DMSO (6 mL) was stirred at room temperature in darkness until the starting compound 1 became undetectable by TLC (The reaction times are indicated in Table 1). Then the reaction mixture was diluted with CH2Cl2 (160–250 mL) and filtered. The filtrate was washed with saturated aqueous NH4Cl (3 × 80 mL) until the aqueous layer remained colourless (concentrated aqueous ammonia (0.25 mL) was added to the saturated aqueous NH4Cl for the isolation of 3Ac. Each time the product was back-extracted from the water layer with few millilitres of CH2Cl2. The combined organic layers were shortly dried over Na2SO4, filtered, and the solvents were evaporated in vacuo. Residual DMSO was removed by several consecutive co-distillations in vacuo with toluene and then ethanol. The product was suspended in boiling cyclohexane (20 mL), cooled down to room temperature, filtered and dried to give the corresponding triazole 3. For analyses the products were crystallized from the solvent indicated below. Reaction times along with the yields of crude and crystallized products are indicated in Table 1.
3-Phenyl-3-(4-phenyl-1H-1,2,3-triazol-1-yl)quinoline-2,4(1H,3H)-dione (3Aa): White solid; mp 274–277 °C (ethanol); IR (cm−1): 3276, 1721 (CO), 1690 (CO), 1613, 1485, 1353, 771, 756; 1H-NMR (DMSO-d6) 7.10–7.21 (m, 2H), 7.29–7.39 (m, 1H), 7.39–7.49 (m, 4H), 7.49–7.57 (m, 3H), 7.60–7.69 (m, 1H), 7.79–7.92 (m, 3H), 8.48 (s, 1H), 11.66 (br s, 1H); 13C-NMR (DMSO-d6) 80.0, 116.7, 119.1, 123.4, 123.5, 125.1, 127.5, 127.9, 128.8, 128.9, 129.5, 129.9, 130.49, 130.52, 136.9, 140.5, 145.3, 166.7, 188.9; HRMS (ESI+) calcd for C23H17N4O2 ([M + H]+): 381.1357, found 381.1355; Anal. Calcd for C23H16N4O2 (380.40): C, 72.62; H, 4.24; N, 14.73; Found: C, 72.59; H, 4.24; N, 14.54.
3-(4-(Hydroxymethyl)-1H-1,2,3-triazol-1-yl)-3-phenylquinoline-2,4(1H,3H)-dione (3Ab): Yellow-brown solid; mp 116–135 °C (benzene); IR (cm−1): 3425, 2915, 1721 (CO), 1684 (CO), 1613, 1595, 1485, 1354, 762; 1H-NMR (DMSO-d6) 4.53 (d, J = 5.4 Hz, 2H), 5.20 (br t, J = 5.4 Hz, 1H), 7.10 (d, J = 8.1 Hz, 1H), 7.16 (dd, J = 7.5, 7.5 Hz, 1H), 7.34–7.45 (m, 2H), 7.45–7.56 (m, 3H), 7.62 (dd, J = 7.5, 7.5 Hz, 1H), 7.75 (s, 1H), 7.84 (d, J = 7.5 Hz, 1H), 11.59 (br s, 1H); 13C-NMR (DMSO-d6) 55.0, 79.6, 116.6, 119.1, 123.4, 124.7, 127.5, 128.7, 129.5, 130.2, 130.5, 136.8, 140.5, 146.8, 166.8, 188.9. Anal. Calcd for C18H14N4O3 (334.33): C, 64.66; H, 4.22; N, 16.76; Found: C, 64.86; H, 4.41; N, 16.62.
3-(4-(3-Aminophenyl)-1H-1,2,3-triazol-1-yl)-3-phenylquinoline-2,4(1H,3H)-dione (3Ac): Brown solid, mp 273–277 °C (DMF-ethanol); IR (cm−1): 3366, 1720 (CO), 1690 (CO); 1613, 1593, 1484, 1353, 774, 757, 697; 1H-NMR (DMSO-d6) 5.16 (br s, 2H), 6.49–6.55 (m, 1H), 6.90 (d, J = 7.7 Hz, 1H), 7.01–7.13 (m, 3H), 7.17 (dd, J = 7.6, 7.6 Hz, 1H), 7.37–7.46 (m, 2H), 7.47–7.56 (m, 3H), 7.59–7.68 (m, 1H), 7.85 (dd, J = 7.8, 1.2 Hz, 1H), 8.27 (s, 1H), 11.59 (br s, 1H); 13C-NMR (DMSO-d6) 79.9, 110.3, 112.8, 113.5, 116.5, 119.1, 122.8, 123.3, 127.4, 128.8, 129.3, 129.4, 129.9, 130.4, 130.9, 136.7, 140.4, 145.9, 149.0, 166.8, 188.9; HRMS (ESI+) calcd for C23H18N5O2 ([M + H]+): 396.1460, found 396.1475.
6-Methoxy-3-phenyl-3-(4-phenyl-1H-1,2,3-triazol-1-yl)quinoline-2,4(1H,3H)-dione (3Ba): Yellow solid; mp 138–145 °C (benzene); IR (cm−1): 3077, 1720 (CO), 1681 (CO), 1502, 1419, 1345, 756, 695; 1H-NMR (DMSO-d6) 3.78 (s, 3H), 7.09 (d, J = 8.5 Hz, 1H), 7.23–7.59 (m, 10H), 7.83 (d, J = 7.4 Hz, 2H), 8.44 (br s, 1H), 11.51 (br s, 1H); 13C-NMR (DMSO-d6) 55.6, 79.7, 109.3, 118.3, 119.5, 123.3, 124.9, 125.1, 127.9, 128.8, 128.9, 129.5, 130.0, 130.48, 130.51, 134.4, 145.2, 155.2, 166.3, 188.9; MS (EI) m/z (%): 411 ([M+1]+, 3), 410 ([M]+, 13), 277 (16), 267 (42), 266 (77), 251 (18), 223 (12), 145 (13), 117 (13), 116 (100), 106 (15), 102 (14), 89 (21), 77 (15); HRMS (ESI+) calcd for C24H19N4O3 ([M + H]+): 411.1457, found 411.1444.
3-(4-(Hydroxymethyl)-1H-1,2,3-triazol-1-yl)-6-methoxy-3-phenylquinoline-2,4(1H,3H)-dione (3Bb): Yellow solid; mp 230–235 °C (crude product); IR (cm−1): 3150, 1718 (CO), 1684 (CO), 1502, 1419, 1345, 1286, 1034, 761; 1H-NMR (DMSO-d6) 3.77 (s, 3H), 4.52 (d, J = 5.1 Hz, 2H), 5.20 (br t, J = 5.1 Hz, 1H), 7.04–7.12 (m, 1H), 7.25–7.33 (m, 2H), 7.36–7.45 (m, 2H), 7.45–7.58 (m, 4H), 7.68 (s, 1H); 13C-NMR (DMSO-d6) 54.9, 55.6, 79.3, 109.2, 118.4, 119.5, 124.7, 124.8, 128.7, 129.5, 130.3, 130.5, 134.6, 146.7, 155.1, 166.3, 188.9; HRMS (ESI+) calcd for C19H17N4O4 ([M + H]+) 365.1250, found 365.1267.
6-Methoxy-3-(4-phenyl-1H-1,2,3-triazol-1-yl)-3-propylquinoline-2,4(1H,3H)-dione (3Ca): Yellow solid; mp 288–315 °C (methanol-N,N-dimethylformamide); IR (cm−1): 3252, 1712 (CO), 1669 (CO), 1503, 1417, 1286, 1240, 1204, 763; 1H-NMR (DMSO-d6) 0.92 (t, J = 7.2 Hz, 3H), 1.21–1.50 (m, 2H), 2.50–2.65 (m, 2H), 3.81 (s, 3H), 7.20 (d, J = 8.9 Hz, 1H), 7.29 (d, J = 2.9 Hz, 1H), 7.31–7.43 (m, 2H), 7.47 (dd, J = 7.5, 7.5 Hz, 2H), 7.82–7.93 (m, 2H), 8.90 (s, 1H), 11.36 (br s, 1H); 13C-NMR (DMSO-d6) 13.7, 16.7, 38.2, 55.6, 74.6, 108.6, 118.4, 118.6, 122.3, 125.1, 125.6, 127.9, 128.9, 130.5, 135.7, 145.6, 155.2, 167.3, 190.5; HRMS (ESI+) calcd for C21H21N4O3 ([M + H]+): 377.1614, found 377.1617.
3-(4-(Hydroxymethyl)-1H-1,2,3-triazol-1-yl)-6-methoxy-3-propylquinoline-2,4(1H,3H)-dione (3Cb): Yellow solid; mp 189–191 °C (benzene-ethanol); IR (cm−1): 3083, 2912, 1715 (CO), 1686 (CO), 1509, 1422, 1335, 1182, 1172, 824; 1H-NMR (DMSO-d6) 0.89 (t, J = 7.2 Hz, 3H), 1.17–1.49 (m, 2H), 2.37–2.62 (m, 2H), 3.80 (s, 3H), 4.55 (br s, 2H), 5.25 (br s, 1H), 7.20 (d, J = 8.9 Hz, 1H), 7.26 (d, J = 3.0 Hz, 1H), 7.37 (dd, J = 8.9, 3.0 Hz, 1H), 8.24 (s, 1H), 9.50 (br s, 1H); 13C-NMR (DMSO-d6) 13.6, 16.7, 38.1, 54.9, 55.6, 74.4, 108.6, 118.5, 118.6, 123.6, 125.4, 135.7, 147.1, 155.1, 167.5, 190.5.; Anal. Calcd for C16H18N4O4 (330.34): C, 58.17; H, 5.49; N, 16.96. Found: C, 57.93; H, 5.45; N, 16.81.
6-Chloro-7-methoxy-3-phenyl-3-(4-phenyl-1H-1,2,3-triazol-1-yl)quinoline-2,4(1H,3H)-dione (3Da): Yellow solid; mp 300–304 °C dec. (DMF-ethanol); IR (cm−1): 3260, 1726 (CO), 1680 (CO), 1610, 1482, 1329, 1275, 1205, 763, 691; 1H-NMR (DMSO-d6) 3.93 (s, 3H), 6.78 (s, 1H), 7.30–7.36 (m, 1H), 7.42–7.48 (m, 4H), 7.52–7.56 (m, 3H), 7.80–7.88 (m, 2H), 8.41 (s, 1H), 11.68 (br s, 1H); 13C-NMR (DMSO-d6) 56.8, 79.2, 100.0, 112.4, 116.7, 123.2, 125.1, 127.8, 128.3, 128.7, 128.8, 129.5, 130.0, 130.3, 130.5, 141.7, 145.2, 160.6, 167.0, 186.4; HRMS (ESI+) calcd for C24H18ClN4O3 ([M + H]+): 445.1067, found 445.1047; Anal. Calcd for C24H17ClN4O3 (444.87): C, 64.80; H, 3.85; N, 12.59. Found: C, 64.55; H, 3.87; N, 12.35.
6-Chloro-3-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)-7-methoxy-3-phenylquinoline-2,4(1H,3H)-dione (3Db): White solid; mp 279–283 °C dec. (ethanol); IR (cm−1): 2838, 1709, 1678, 1613, 1596, 1415, 1354, 1279, 1222, 1035; 1H-NMR (DMSO-d6) 3.92 (s, 3H), 4.52 (d, J = 5.0 Hz, 2H), 5.19 (br t, J = 5.0 Hz, 1H), 6.76 (s, 1H), 7.33–7.45 (m, 2H), 7.46–7.58 (m, 3H), 7.68 (s, 1H), 7.83 (s, 1H), 11.63 (br s, 1H); 13C-NMR (DMSO-d6) 54.9, 56.8, 78.9, 100.1, 112.5, 116.7, 124.6, 128.3, 128.6, 129.5, 130.3, 130.5, 141.8, 146.8, 160.6, 167.0, 186.5; Anal. Calcd for C19H15ClN4O4 (398.80): C, 57.22; H, 3.79; N, 14.05. Found: C, 57.05; H, 3.75; N, 13.92.
1-Benzyl-3-phenyl-3-(4-phenyl-1H-1,2,3-triazol-1-yl)quinoline-2,4(1H,3H)-dione (3Ea): Yellow-brown solid; mp 105–113 °C (benzene-cyclohexane) IR (cm−1): 3061, 1714 (CO), 1679 (CO), 1600, 1468, 1453, 1373, 1312, 759, 695; 1H-NMR (DMSO-d6) 5.34 (d, J = 16.6 Hz, 1H), 5.48 (d, J = 16.6 Hz, 1H), 7.12–7.40 (m, 10H), 7.40–7.56 (m, 5H), 7.63 (dd, J = 7.7, 7.7 Hz, 1H), 7.84 (d, J = 7.5 Hz, 2H), 7.99 (d, J = 7.5 Hz, 1H), 8.56 (s, 1H); 13C-NMR (DMSO-d6) 26.3, 46.6, 80.2, 116.6, 120.8, 123.4, 124.0, 125.1, 126.7, 127.4, 127.9, 128.3, 128.6, 128.9, 129.5, 129.9, 130.5, 130.7, 135.7, 136.9, 140.8, 145.4, 166.9, 188.4; MS (EI) m/z (%): 471 ([M+1]+, 1), 470 ([M]+, 3), 326 (10), 206 (9), 116 (32), 92 (8), 91 (100), 77 (8); Anal. Calcd for C30H22N4O2 (470.52): C, 76.58; H, 4.71; N, 11.91; Found: C, 76.33; H, 4.73; N, 11.88.
1-Benzyl-3-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)-3-phenylquinoline-2,4(1H,3H)-dione (3Eb). White solid; mp 184–187 °C (benzene-ethanol); IR (cm−1): 1721 (CO), 1691 (CO), 1601, 1468, 1453, 1373, 1311, 1027, 763, 693; 1H-NMR (DMSO-d6) 4.56 (d, J = 5.1 Hz, 2H), 5.23 (br t, J = 5.1 Hz, 1H), 5.31 (d, J = 16.7 Hz, 1H), 5.46 (d, J = 16.6 Hz, 1H), 7.15–7.39 (m, 9H), 7.41–7.55 (m, 3H), 7.61 (dd, J = 7.5, 7.5 Hz, 1H), 7.88 (s, 1H), 7.96 (d, J = 7.2 Hz, 1H); 13C-NMR (DMSO-d6) 46.7, 55.0, 80.0, 116.6, 121.0, 123.9, 124.9, 126.7, 127.4, 127.9, 128.6, 128.9, 129.5, 130.2, 130.6, 135.8, 136.8, 140.9, 147.0, 167.0, 188.5; MS (EI) m/z (%): 424 ([M]+, 2), 327 (16), 326 (16), 325 (9), 303 (7), 146 (7), 104 (10), 103 (7), 92 (9), 91 (100), 77 (11), 65 (10); Anal. Calcd for C25H20N4O3 (424.45): C, 70.74; H, 4.75; N, 13.20; Found: C, 70.49; H, 4.81; N, 12.91.

3.7. One-Pot Synthesis of 3-Phenyl-3-(4-phenyl-1H-1,2,3-triazol-1-yl)quinoline-2,4(1H,3H)-dione (3Aa) Starting from 3-Bromo-3-phenylquinoline-2,4(1H,3H)-dione (6A)

A mixture of 3-bromo-3-phenylquinoline-2,4(1H,3H)-dione (6A, 316 mg, 1.00 mmol), pulverized NaN3 (130 mg, 2.00 mmol), phenylacetylene (2a, 103 mg, 1.01 mmol), CuSO4.5H2O (25 mg, 0.10 mmol), copper powder (280 mg, 4.41 mmol) and dimethyl sulfoxide (3.0 mL) was stirred in darkness for 20 h and then diluted with CH2Cl2 (80 mL). The reaction mixture was filtered and the filtrate was repeatedly extracted with saturated aqueous NH4Cl, until the aqueous phase remains colourless (totally 50 mL). The collected aqueous layer was back-extracted with CH2Cl2 (3 × 10 mL). The combined organic layers were dried over Na2SO4, filtered and evaporated in vacuo. Residual DMSO was removed by consecutive co-distillations in vacuo with toluene (2 × 15 mL) and then ethanol (2 × 15 mL). The product was suspended in cyclohexane (10 mL). The suspension was shortly boiled, cooled down to room temperature and the product was collected by filtration. Recrystallization from ethanol-acetic acid afforded pure 3Aa (162 mg, 43%); mp 250–270 °C.

3.8. N-(3-(1-(1,2,3,4-Tetrahydro-2,4-dioxo-3-phenylquinolin-3-yl)-1H-1,2,3-triazol-4-yl)phenyl)acetamide (3Ae).

A suspension of 3-(4-(3-aminophenyl)-1H-1,2,3-triazol-1-yl)-3-phenylquinoline-2,4(1H,3H)-dione (3Ac, 99 mg, 0.25 mmol) in a mixture of ethyl acetate (0.5 mL) and pyridine (0.3 mL) was heated to the boiling point. Acetic anhydride (62 mmol, 6 mL) was added portion wise under shaking. The reaction mixture was cooled down to room temperature, left overnight and evaporated in vacuo. The residue was suspended in hot methanol (2 mL), cooled down to room temperature and product 3Ae (72.3 mg, 65%) was collected by filtration: light brown powder; mp 307–314 °C (dec.); IR (cm−1): 3319, 1719, 1678, 1615, 1594, 1485, 1446, 1369, 784; 1H-NMR (DMSO-d6) d 2.06 (s, 3H), 7.11 (d, J = 8.1 Hz, 1H), 7.17 (dd, J = 7.5, 7.5 Hz, 1H), 7.35 (dd, J = 7.8, 7.8 Hz, 1H), 7.39–7.48 (m, 3H), 7.48–7.59 (m, 4H), 7.59–7.68 (m, 1H), 7.84 (dd, J = 7.7, 0.9 Hz, 1H), 8.10 (br s, 1H), 8.46 (s, 1H), 10.03 (br s, 1H), 11.62 (br s, 1H); 13C-NMR (DMSO-d6) d 24.0, 80.0, 115.5, 116.6, 118.4, 119.2, 119.8, 123.3, 127.4, 128.8, 129.2, 129.4, 129.9, 130.4, 130.8, 136.7, 139.8, 140.4, 145.2, 166.7, 168.3, 188.8; Anal. Calcd for C25H19N5O3 (437.45): C, 68.64; H, 4.38; N, 16.01. Found: C, 68.58; H, 4.39; N, 15.93.

4. Conclusions

In conclusion, 3-azidoquinoline-2,4(1H,3H)-diones readily undergo copper(I)-catalyzed [3 + 2] cycloaddition reaction with terminal alkynes to give the corresponding 1,4-disubstituted-1,2,3-triazoles.

Acknowledgements

This study was supported by the Ministry of Education, Youth and Sports of the Czech Republic (Project MSM7088352101 and Joint Project Nr 9-06-3 of Programme KONTAKT), and the Slovenian Research Agency (Project P1-0230-0103 and Joint Project BI-CZ/07-08-018). This work was also partly supported through the infrastructure of the EN-FIST Centre of Excellence, Ljubljana. The authors thank Bogdan Kralj and Dušan Žigon (Mass Spectrometry Center, Jožef Stefan Institute, Ljubljana, Slovenia) for mass spectral measurements and Marijan Kočevar for the suport in characterization of azides.

References and Notes

  1. Kafka, S.; Klásek, A.; Polis, J.; Košmrlj, J. Syntheses of 3-aminoquinoline-2,4(1H,3H)-diones. Heterocycles 2002, 57, 1659–1682. [Google Scholar] [CrossRef]
  2. Gololobov, Y.G.; Kasukhin, L.F. Recent advances in the Staudinger reaction. Tetrahedron 1992, 48, 1353–1406. [Google Scholar] [CrossRef]
  3. L’abbé, G. Are azidocumulenes accessible? Bull. Soc. Chim. Belg. 1984, 93, 579–592. [Google Scholar]
  4. Tornøe, C.W.; Christensen, C.; Meldal, M. Peptidotriazoles on solid phase: [1,2,3]-Triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J. Org. Chem. 2002, 67, 3057–3064. [Google Scholar] [CrossRef]
  5. Rostovtsev, V.V.; Green, L.G.; Fokin, V.V.; Sharpless, K.B. A stepwise Huisgen cycloaddition process: Copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew. Chem. Int. Ed. 2002, 41, 2596–2599. [Google Scholar]
  6. Meldal, M.; Tornøe, C.W. Cu-catalyzed azide-alkyne cycloaddition. Chem. Rev. 2008, 108, 2952–3015. [Google Scholar] [CrossRef]
  7. Hein, J.E.; Fokin, V.V. Copper-catalyzed azide-alkyne cycloaddition (CuAAC) and beyond: New reactivity of copper(I) acetylides. Chem. Soc. Rev. 2010, 39, 1302–1315. [Google Scholar] [CrossRef]
  8. Bock, V.D.; Hiemstra, H.; van Maarseveen, J.H. CuI-catalyzed alkyne-azide “click” cycloadditions from a mechanistic and synthetic perspective. Eur. J. Org. Chem. 2006, 2006, 51–68. [Google Scholar]
  9. Appukkuttan, P.; Van der Eycken, E. Recent developments in microwave-assisted, transition-metal-catalysed C–C and C–N bond-forming reactions. Eur. J. Org. Chem. 2008, 2008, 1133–1155. [Google Scholar] [CrossRef]
  10. Kappe, C.O.; Van der Eycken, E. Click chemistry under non-classical reaction conditions. Chem. Soc. Rev. 2010, 39, 1280–1290. [Google Scholar] [CrossRef]
  11. Urankar, D.; Košmrlj, J. Concise and diversity-oriented synthesis of ligand arm-functionalized azoamides. J. Comb. Chem. 2008, 10, 981–985. [Google Scholar] [CrossRef]
  12. Urankar, D.; Košmrlj, J. Preparation of diazenecarboxamide-carboplatin conjugates by click chemistry. Inorg. Chim. Acta 2010, 363, 3817–3822. [Google Scholar] [CrossRef]
  13. Alonso, F.; Moglie, Y.; Radivoy, G.; Yus, M. Multicomponent synthesis of 1,2,3-triazoles in water catalyzed by copper nanoparticles on activated carbon. Adv. Synth. Catal. 2010, 352, 3208–3214. [Google Scholar] [CrossRef]
  14. Kumar, D.; Patel, G.; Reddy, V.B. Greener and expeditious synthesis of 1,4-disubstituted 1,2,3-triazoles from terminal acetylenes and in situ generated alpha-azido ketones. Synlett 2009, 3, 399–402. [Google Scholar]
  15. Kashinath, D.; Budin, G.; Baati, R.; Meunier, S.; Wagner, A. Azidation of β-carbonyl lactones and lactams. Tetrahedron Lett. 2009, 50, 5379–5381. [Google Scholar]
  16. Bräse, S.; Gil, C.; Knepper, K.; Zimmermann, V. Organic azides: An exploding diversity of a unique class of compounds. Angew. Chem. Int. Ed. 2005, 44, 5188–5240. [Google Scholar] [CrossRef]
  17. Bräse, S.; Banert, K. Organic Azides: Syntheses and Applications; John Wiley & Sons: Chichester, UK, 2010. [Google Scholar]
  18. Stadlbauer, W.; Schmut, O.; Kappe, T. Synthesis of benzofurans by cyclodehydrogenation of phenylmalonyl heterocyclics. Monatsh. Chem. 1980, 111, 1005–1013. [Google Scholar]
  19. Stadlbauer, W.; Kappe, T. Synthesis of benzofurans by cyclodehydrogenation of phenylmalonyl heterocyclics. Monatsh. Chem. 1985, 116, 1005–1015. [Google Scholar] [CrossRef]
  20. Stadlbauer, W.; Laschober, R.; Lutschounig, H.; Schindler, G.; Kappe, T. Organic azides in heterocycle synthesis. Part 16. Halogenation reactions in position 3 of quinoline-2,4-dione systems by electrophilic substitution and halogen exchange. Monatsh. Chem. 1992, 123, 617–636. [Google Scholar]
  • Sample Availability: Samples of the compounds 16 are available from the authors.

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MDPI and ACS Style

Kafka, S.; Hauke, S.; Salcinovic, A.; Soidinsalo, O.; Urankar, D.; Kosmrlj, J. Copper(I)-Catalyzed [ 3+ 2] Cycloaddition of 3-Azidoquinoline-2,4(1H,3H)-diones with Terminal Alkynes. Molecules 2011, 16, 4070-4081. https://doi.org/10.3390/molecules16054070

AMA Style

Kafka S, Hauke S, Salcinovic A, Soidinsalo O, Urankar D, Kosmrlj J. Copper(I)-Catalyzed [ 3+ 2] Cycloaddition of 3-Azidoquinoline-2,4(1H,3H)-diones with Terminal Alkynes. Molecules. 2011; 16(5):4070-4081. https://doi.org/10.3390/molecules16054070

Chicago/Turabian Style

Kafka, Stanislav, Sylvia Hauke, Arjana Salcinovic, Otto Soidinsalo, Damijana Urankar, and Janez Kosmrlj. 2011. "Copper(I)-Catalyzed [ 3+ 2] Cycloaddition of 3-Azidoquinoline-2,4(1H,3H)-diones with Terminal Alkynes" Molecules 16, no. 5: 4070-4081. https://doi.org/10.3390/molecules16054070

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