Startseite A convenient synthesis of trifluoromethyl-substituted quinolino[8,7-h]quinolines and quinolino[7,8-h]quinolines
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A convenient synthesis of trifluoromethyl-substituted quinolino[8,7-h]quinolines and quinolino[7,8-h]quinolines

  • Bianca Seitz ORCID logo und Gerhard Maas ORCID logo EMAIL logo
Veröffentlicht/Copyright: 6. September 2021
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Zeitschrift für Naturforschung B
Aus der Zeitschrift Zeitschrift für Naturforschung B Band 76 Heft 9

Abstract

Bis(trifluoromethyl)-substituted quinolino[8,7-h]quinolines and quinolino[7,8-h]quinolines have been prepared from 3-substituted 1-CF3-prop-2-yne 1-iminium triflate salts and 1,5- and 1,8-diaminonaphthalene, respectively, by a twofold pyridoannelation sequence. These transformations do not require any additional reagent and can be performed at remarkable mild thermal conditions.

Keywords: acetylenic iminium salts; cyclocondensation; organofluorine chemistry; quinolino-quinolines; trifluoromethyl-containing building blocks

1 Introduction

Quinolino[8,7-h]quinolines (1) and quinolino[7,8-h]quinolines (2) are aza-heteroaromatic compounds consisting of two fused quinoline moieties (Figure 1). Reliable syntheses and solid-state structures of the parent systems have been published by Staab and coworkers more than 30 years ago [1, 2]. In the meantime, specific properties and applications of both compound classes have been studied.

Figure 1: Molecular framework of quinolino[8,7-h]quinoline (also named 4,10-diazachrysene) (1) and quinolino[7,8-h]quinoline (2).
Figure 1:

Molecular framework of quinolino[8,7-h]quinoline (also named 4,10-diazachrysene) (1) and quinolino[7,8-h]quinoline (2).

Compounds with the quinolino[8,7-h]quinoline core unit 1 have been claimed as electroactive components in organic light-emitting devices [3], [4], [5]. Several 1,7-bis(alkylamino)-quinolino[8,7-h]quinolines were studied as potential small-molecule therapeutics to combat Ebola virus disease [6], [7], [8], [9], Malaria (Plasmodium falciparum) [6] and Botulinum neurotoxin [6]. A compound of the same type was identified as an inhibitor of 4′-phosphopantetheinyl transferase of Mycobacterium tuberculosis [10]. Furthermore, the influence of fluorine-substitution on the mutagenicity of quinolino[8,7-h]quinolines has been studied [11].

The molecular skeleton of quinolino[8,7-h]quinoline (1) can be obtained by a twofold pyridoannelation of 1,5-diaminonaphthalene using classical approaches to quinolines, such as Skraup and Doebner-von Miller reactions [12]. Derivatives of the parent system, which is obtained in modest yield from this diamine and glycerol in a Skraup reaction [13], have been prepared, inter alia, by dibromination [3] or nitration [11] and were used for further transformations. Starting from 1,5-diaminonaphthalene and β-ketoesters [4], [5], [6] or DMAD [4, 7], a twofold Conrad-Limpach cyclization leads to 4(1H)-quinolones, which can be converted into 1,7-dichloro-quinolino[8,7-h]quinolines. By SNAr reactions of the latter, a wide range of 1,7-bis(alkylamino) and other heteroatom-substituted derivatives became available.

Quinolino[7,8-h]quinoline (2) and derivatives thereof represent a new type of proton sponges and superbases [1, 14], [15], [16]. The coordination properties of 2 have been documented by reports on chelate complexes BF2-2 and BF2-(4,9-dichloro-2) [17] and various transition-metal complexes [18, 19]. The parent compound itself can be prepared from 1,8-diaminonaphthalene and dimethyl acetylenedicarboxylate in 5–6 steps [1, 17, 20]. Notably, the thermal (120 °C) reaction of 1,8-diaminonaphthalene and 3,3-bis(methylthio)acrolein in glacial acetic acid furnished 2,11-bis(methylthio)-2 in one step in a moderate yield; 3,9-bis(methylthio)-1 was obtained analogously from 1,5-diaminonaphthalene [21].

Trifluoromethyl derivatives of 1 and 2 have not been reported so far. Due to some unique properties of the C‒F bond and fluoroalkyl substituents [22], it can be expected that the presence of electron-withdrawing CF3 substituents modulates several (physico)chemical properties of these condensed heteroaromatic systems, such as lowering of the LUMO energy level, reduced basicity and ligand donor strength. Furthermore, fluoro-substituted organic compounds play a significant role in contemporary medicinal chemistry [23].

In a preceding paper, we have shown that a wide range of 2-substituted 4-trifluoromethyl-quinolines can be assembled easily from 1-CF3-prop-2-yne-N,N-dimethyliminium triflates and aniline or its ring-substituted derivatives [24]. This transformation proceeds via an aza-Michael addition followed by a thermally induced intramolecular cyclocondensation of the so-formed vinamidinium ion; a certain analogy to the classical Doebner-von Miller synthesis of quinolines from primary aromatic amines and α,β-unsaturated carbonyl compounds can be recognized. In the same manner, we were able to prepare 4-CF3-benzo[f]quinolines from 1-CF3-prop-2-yne 1-iminium salts and 1-aminonaphthalene [24]. Based on these results, we expected that the use of diaminonaphthalenes would allow the twofold pyridoannelation of the naphthalene ring system. Here we report that bis(trifluoromethyl)-quinolino[8,7-h]quinolines and quinolino[7,8-h]quinolines can indeed be obtained, when naphthalene-1,5-diamine and naphthalene-1,8-diamine, respectively, are applied as the aromatic amine component.

2 Results and discussion

2.1 Synthesis of quinolino[8,7-h]quinolines 6

In a previous study [24] we have found, that the one-pot consecutive reaction of 1-CF3-substituted propyniminium salt 3a, which can be prepared from the corresponding alkynyl imine by N-methylation with methyl triflate [25], and p-phenylenediamine in a 2:1 M ratio yielded, after aqueous workup, quinolines 4 and 5 (Scheme 1) in moderate yields. Obviously, only one pyridoannelation has occurred, and the two products result from a nucleophilic addition of the second NH2 group at carbon atom C-3 (aza-Michael reaction) as well as C-1 (transimination) of the propyne iminium ion. The vinamidinium ion resulting from C-3 attack was not able to undergo intramolecular cyclization under the given thermal conditions; it was rather transformed into 4 during aqueous workup.

Scheme 1: Reaction of propyniminium salt 3a with p-phenylenediamine in a 2:1 M ratio [24].
Scheme 1:

Reaction of propyniminium salt 3a with p-phenylenediamine in a 2:1 M ratio [24].

Following our established protocol, we have now combined propyniminium salts 3a–e and 1,5-diaminonaphthalene in a 2:1 M ratio (Scheme 2). The reactions were run in acetonitrile solution and monitored by 19F NMR spectroscopy. The solutions were first kept at room temperature to assure the complete conversion of salts 3 into vinamidinium salts resulting from an aza-Michael addition. For the adducts formed from 3a–d, a subsequent thermal activation was required to induce the twofold pyridoannelation step leading to quinolino[8,7-h]quinolines 6a–d in good yields. In the case of tert-butyl-substituted 6e, no heating was required, and the whole reaction sequence could be performed at room temperature. As we will point out elsewhere [26], the bulkiness of the tert-butyl group probably fixes the Z(C2=C3) configuration of the 1-CF3-3-tert-butyl-vinamidinium (or bis-vinamidinium) intermediate and therefore facilitates the intramolecular cyclization.

Scheme 2: Synthesis of quinolino[8,7-h]quinolines 6. Conditions for 6a–d: 1. room temp./1 h, 2. 60 °C/72 h; for 6e: room temp./15 h.
Scheme 2:

Synthesis of quinolino[8,7-h]quinolines 6. Conditions for 6a–d: 1. room temp./1 h, 2. 60 °C/72 h; for 6e: room temp./15 h.

The quinolino[8,7-h]quinolines 6a‒c are high-melting solids, which precipitated from the reaction solution. Since they are apparently insoluble in almost all common organic solvents, they could not be obtained in analytically pure quality. At least in THF-d 8, acceptable 1H and 19F NMR spectra of 6a–c could be recorded; they and the mass spectra confirmed the expected constitution of the products. For the more soluble cyclopropyl- (6d) and tert-butyl (6e) substituted tetracycles, 13C NMR spectra provided additional structural support (see Table 1 and accompanying text).

Table 1:

NMR data for compounds 6e and 8b (in CDCl3).

Atom position δ (ppm) and J (Hz) Atom position δ (ppm) and J (Hz)
1H NMR
2, 8 7.98 (s) 3, 10 7.99 (s)
6, 12 8.32 (dq, 3 J H,H = 9.3, 5 J H,F = 2.2) 5, 8 8.27 (dq, 3 J H,H = 8.8, 5 J H,F = 1.9)
5, 11 9.57 (d, 3 J H,H = 9.2) 6, 7 7.97 (d, 3 J H,H = 8.9)
CMe3 1.62 (s) CMe3 1.61 (s)
13C{1H} NMRa
1, 7 134.7 (q, 2 J C,F = 31.2) 4, 9 134.0 (q, 2 J C,F = 30.9)
2, 8 115.8 (q, 3 J C,F = 5.2) 3, 10b 115.0 (q, 3 J C,F = 5.2)
3, 9b 168.3 (s) 2, 11c 168.1 (s)
4a, 10ac 145.5 (s) 12a, 12cc 147.3 (s)
6, 12 122.0 (q, 4 J C,F = 2.4) 5, 8b 123.9 (q, 4 J C,F = 2.5)
6, 7b 127.9 (s)
CMe 3, CMe3 30.4 (s), 39.1 (s) CMe 3, CMe3 30.6 (s), 39.2 (s)
CF3 124.1 (q, 1 J C,F = 275) CF3 124.2 (q, 1 J C,F = 275)
Other signals 120.8 (s), 124.8 (s), 131.9 (s)

(C5(11), C-4b(10-b), C-6a(12a))d 		Other signals 121.4 (s, Cq), 127.6 (s, Cq), 135.2 (s, Cq)

(C-4a(8a), C-6a, C-12b)d,e
19F NMR −62.0 −61.5

  1. aSignal multiplicities in the proton-decoupled 13C spectra are given in parentheses. bAssignments were based on C,H correlation (HSQC) spectra. cAssignment based on ChemNMR prediction [29]. dSignals were not assigned individually. eChemNMR predicts the following chemical shifts for 8b: C-4a(6a) 128.1, C-6a 135.8, C-12b 129.6 ppm.

2.2 Synthesis of quinolino[7,8-h]quinolines 8

When iminium salt 3a and 1,8-diaminonaphthalene were combined in acetonitrile, the color of the solution soon changed to orange and brown. In the 19F NMR spectra, two new signals of equal intensity appeared. After 20 h at room temperature, the voluminous precipitate was isolated and identified as the alkynyliminyl-substituted benzo[h]quinoline 7a (Scheme 3). The presence of the alkynylimine moiety was indicated by 13C NMR signals at δ = 79.6 and 99.9 ppm for the C(sp) carbon atoms and a quartet signal at 138.8 ppm (2 J C,F = 38.7 Hz) for the imine carbon atom. The 19F NMR spectra showed the same two signals as in the reaction control spectra: δ = −61.9 ppm for the CF3 group in the pyridine moiety and −72.1 ppm for the imine-bonded CF3 group. These and the remaining NMR data are in agreement with other 4-CF3 benzo[h]quinolines and of compound 5 (Scheme 1), which had been characterized by an X-ray diffraction analysis [24].

Scheme 3: Reaction of 3a with 1,8-diaminonaphthalene.
Scheme 3:

Reaction of 3a with 1,8-diaminonaphthalene.

When the reaction mixture containing the precipitated benzo[h]quinoline 7a was heated at 60 °C, a new 19F NMR signal was observed which gradually replaced the two signals of 7a. After a reaction time of 36 h, a new product was isolated, to which the structure of the quinolino[7,8-h]quinoline 8a could be assigned based on the spectroscopic and analytical data. The number of signals in the NMR spectra is in agreement with the C 2v-symmetrical structure. NMR signal assignments are given in Table 1 (see next section). Obviously, 8a cannot be formed by a simple cyclization of the N-aryl-alkynylimine moiety of 7a, because this would result in an unsymmetrical tetracyclic ring system. We assume that under the reaction conditions, i.e. heating of the reaction mixture that contains both solid 7a and dimethylammonium triflate, the imine formation (from an arylamine and 3a) is reversed and the two components now react via an aza-Michael addition and an intramolecular cyclization to complete the second pyridoannelation step.

Similar to the 2,11-diphenylquinolino[7,8-h]quinoline 8a, the 2,11-di-tert-butyl analogue 8b could be prepared from iminium salt 3e and 1,8-diaminonaphthalene in 73% yield (Scheme 4). Only a ∼10% conversion was noted after 18 h at 22 °C, and the reaction required four days at 40 °C followed by two days to 60 °C to come to completion – in contrast to the formation of 6e from 1,5-diaminonaphthalene at room temperature. Obviously, the chosen reaction conditions were not yet optimal; instead of the three-stage procedure and in order to save time, the reaction might be performed at 60–80 °C directly.

Scheme 4: Synthesis of quinolino[7,8-h]quinoline 8b.
Scheme 4:

Synthesis of quinolino[7,8-h]quinoline 8b.

2.3 Comparison of the NMR data of 6e and 8b

The 1H, 13C and 19F NMR data of the constitutional isomers 6e (a C 2h-symmetrical molecule) and 8b (C 2v symmetry) are juxtaposed in Table 1. Evidently, most of the chemical shifts and multiplicities of corresponding signals in the two compounds are very similar. In the 1H spectra, only the chemical shifts of 5-H,11-H in 6e versus 6-H,7-H in 8b differ markedly; the strong deshielding of protons 5-H,11-H in 6e is characteristic of the benzo[h]quinoline structure [24, 27, 28]. For the 13C signal assignments, beside C,H correlation spectra the magnitude of C,F coupling constants was helpful. Their values do not differ significantly from those found in simple 4-CF3-quinolines and 4-CF3-benzo[h]quinolines [24]. A 13C criterion that allows to distinguish the constitution of the two constitutional isomers is provided by the number of signals for the ring-junction quaternary carbons, which is 3 in 6e and 4 in 8b.

3 Conclusion

The reaction of 1-CF3-prop-2-yne 1-iminium triflates with the appropriate diaminonaphthalene, including a twofold pyridoannelation strategy, represents the first synthesis of bis(trifluoromethyl)-substituted quinolino[8,7-h]quinolines and quinolino[7,8-h]quinolines. These reactions do not require any additional reagent or catalyst and can be performed with rather moderate thermal activation, compared to other cyclization approaches to these ring systems. The influence of the trifluoromethyl substituents on (physico)chemical properties and eventually bioactivities of these compounds should be worth being studied.

4 Experimental section

4.1 General information

All reactions involving the moisture-sensitive iminium salts were carried out in rigorously dried glassware under an argon atmosphere using Schlenk techniques. Acetonitrile was dried and stored over molecular sieves (3 Å) under argon. Melting points were determined in open capillaries with a Büchi B-540 instrument at a heating rate of 2 K min−1.

IR spectra were recorded on a Bruker Vector 22 FT-IR spectrometer. Wavenumbers ( ν ˜ max, cm−1) of selected absorptions are reported, relative intensities are given as s (strong), m (medium) and w (weak). NMR spectra were recorded on a Bruker Avance 400 spectrometer (operating at 400.13 MHz for 1H, 100.61 MHz for 13C, 376.47 MHz for 19F) and a Bruker Avance 500 (1H: 500.14 MHz, 13C: 125.77 MHz) instrument. NMR chemical shifts (δ) are reported in ppm; for the 1H and 13C spectra the solvent signal served for internal calibration [1H NMR: δ(CHCl3) = 7.26 (s), δ(THF) = 1.72 ppm; 13C NMR: δ(CDCl3) = 77.16 (t), δ(THF-d 8) = 25.31 (quint) and 67.21 (quint) ppm]; for 19F NMR spectra internal hexafluorobenzene was used (δ(C6F6) = −162.90 ppm). 13C and 19F NMR spectra were recorded in the proton-decoupled mode. Mass spectra were recorded with the following instruments: Finnigan MAT SSQ 7000 (CI), SolariX (HRMS-MALDI). Propyniminium salts 3 were prepared as described in lit [25]. The diaminonaphthalenes were commercially available.

4.2 1,7-Bis(trifluoromethyl)quinolino[8,7-h]quinolines 6; general procedure

A solution of a propyne iminium triflate 3 (2.0 mol equivalents) in dry acetonitrile (6 mL) was placed in an oven-dried Schlenk tube flushed with argon, and 1,5-diaminonaphthalene (1.0 mol equivalents) was added. An immediate color change from colorless to orange was observed. The solution was stirred for 1 h at room temperature; a colorless precipitate began to form after 10–30 min (except for the reaction of 3d). Subsequently, the stirred mixture was brought to 60 °C and kept at this temperature for three days. After cooling to r.t., the solid product was filtered off and washed with a small volume of acetonitrile. Due to their very low solubility in common organic solvents, further purification of products 6a–d by crystallization or chromatographic methods was not viable.

4.2.1 3,9-Diphenyl-1,7-bis(trifluoromethyl)quinolino[8,7-h]quinoline (6a)

Prepared from propyne iminium salt 3a (675 mg, 1.80 mmol) and 1,5-diaminonaphthalene (138 mg, 0.87 mmol). A beige solid was obtained (366 mg, 0.71 mmol, 81% yield), m.p. 329 °C. ‒ IR (KBr): ν ˜  = 1611 (w), 1371 (m), 1265 (m), 1200 (m), 1145 (m), 1122 (s), 683 (m) cm−1. ‒ 1H NMR (THF-d 8, 500 MHz): δ = 7.51–7.56 (m, 2H), 7.58–7.63 (m, 4H), 8.43 (dq, 3 J H,H = 9.3 Hz, 5 J H,F = 2.2 Hz, 2H, 6,12-H), 8.46–8.49 (m, 4H), 8.54 (s, 2H, 2,8-H), 9.74 (d, 3 J H,H = 9.3 Hz, 2H, 5.11-H). ‒ 19F NMR (THF-d 8): δ = −60.0. ‒ MS (CI, 100 eV): m/z (%) = 519 (100) [M+H]+, 518 (18) [M]+. ‒ HRMS (MALDI): m/z = 519.12872 [M+H]+; calcd. for [C30H17F6N2]+: 519.12959. ‒ Analysis calcd. for C30H16F6N2 (518.46): C 69.50, H 3.11, N 5.40; found C 69.14, H 3.27, N 5.77.

4.2.2 3,9-Bis(3-bromophenyl)-1,7-bis(trifluoromethyl)quinolino[8,7-h]quinoline (6b)

Prepared from iminium salt 3b (640 mg, 1.41 mmol) and 1,5-diaminonaphthalene (112 mg, 0.71 mmol). Pale yellow solid (402 mg, 0.59 mmol, 84% yield), m.p. 345 °C. ‒ IR (KBr): ν ˜  = 1612 (m), 1563 (m), 1391 (m), 1368 (s), 1305 (m), 1269 (s), 1199 (m), 1149 (s), 1120 (s), 884 (m), 842 (m), 787 (m), 763 (m), 664 (m) cm−1. ‒ 1H NMR (THF-d 8, 500 MHz): δ = 7.53 (t, 3 J H,H = 7.9 Hz, 2H), 7.70–7.74 (m, 2H), 8.43 (d, 3 J H,H = 7.8 Hz, 2H), 8.47 (dq, 3 J H,H = 9.3 Hz, 5 J H,F = 2.2 Hz, 2H, 6,12-H), 8.57 (s, 2H), 8.68–8.71 (m, 2H), 9.75 (d, 3 J H,H = 9.3 Hz, 2H, 5,11-H). ‒ 19F NMR (THF-d 8): δ = −59.9. ‒ HRMS (MALDI): m/z = 678.94669 [M+H]+ (81Br81Br), 676.94844 [M+H]+ (79Br81Br), 674.95067 [M+H]+ (79Br79Br); calcd. 678.94651, 676.94856, 674.9506. ‒ Analysis calcd. for C30H14Br2F6N2 (676.24): C 53.28, H 2.09, N 4.14; found C 53.04, H 2.24, N 4.21.

4.2.3 3,9-Bis(4-methoxyphenyl)-1,7-bis(trifluoromethyl)quinolino[8,7-h]quinoline (6c)

Prepared from iminium salt 3c (580 mg, 1.43 mmol) and 1,5-diaminonaphthalene (113 mg, 0.72 mmol). Yellow solid (344 mg, 0.59 mmol, 83% yield), m.p. 324 °C. ‒ IR (KBr): ν ˜  = 1609 (s), 1570 (m), 1493 (m), 1413 (m), 1373 (s), 1301 (m), 1268 (s), 1251 (s), 1198 (m), 1179 (m), 1154 (s), 1118 (s), 1032 (m), 837 (m) cm−1. ‒ 1H NMR (THF-d 8, 500 MHz, 340 K): δ = 3.91 (s, 6H, OMe), 7.14 (d, 3 J H,H = 8.7 Hz, 4H, Haryl ortho to OMe), 8.36 (d, 3 J H,H = 9.3 Hz, 2H, 6,12-H), 8.41–8.47 (m, 6H, 2,8-H, Haryl meta to OMe), 9.66 (d, 3 J H,H = 9.2 Hz, 2H, 5,11-H). ‒ 19F NMR (THF-d 8): δ = −60.0. ‒ HRMS (MALDI): m/z = 579.15043 [M+H]+, 578.14276 [M]+; calcd. for [C32H21F6N2O2]+: 579.15072, [C32H20F6N2O2]+: 578.14289.

4.2.4 3,9-Dicyclopropyl-1,7-bis(trifluoromethyl)quinolino[8,7-h]quinoline (6d)

Prepared from iminium salt 3d (400 mg, 1.18 mmol) and 1,5-diaminonaphthalene (93 mg, 0.59 mmol). As no precipitate was present at the end of the reaction, the solvent was evaporated in vacuo and the solid residue was washed with a small volume of cold acetonitrile. The product was obtained as a beige solid (197 mg, 0.44 mmol, 75% yield), m.p. 266 °C (decomp.). ‒ IR (KBr): ν ˜  = 1614 (m), 1583 (m), 1495 (m), 1425 (m), 1408 (m), 1361 (m), 1328 (s), 1299 (s), 1263 (m), 1213 (m), 1192 (m), 1150 (s), 1130 (s), 1080 (m), 1024 (m), 988 (m), 901 (m), 864 (m), 840 (m), 818 (m), 765 (m), 706 (m) cm−1. ‒ 1H NMR (CDCl3, 500 MHz): δ = 1.20–1.27 (m, 4Hc-propyl), 1.40–1.45 (m, 4Hc-propyl), 2.37 (tt, 3 J H,H = 8.0 Hz, 3 J H,H = 4.7 Hz, 2H, CHc-propyl), 7.76 (s, 2H, 2,8-H), 8.24 (dq, 3 J H,H = 9.3 Hz, 5 J H,F = 2.2 Hz, 2H, 6,12-H), 9.35 (d, 3 J H,H = 9.2 Hz, 2H, 5,11-H). ‒ 13C{1H} NMR (CDCl3, 126 MHz): δ = 11.8 (s), 18.4 (s), 118.3 (q, 3 J C,F = 5.3 Hz), 121.1 (s), 122.0 (q, 4 J C,F = 2.3 Hz), 123.97 (s), 124.01 (q, 1 J C,F = 275 Hz, CF3), 131.5 (s), 134.4 (q, 2 J C,F = 31.5 Hz), 146.4, 162.5. ‒ 19F NMR (CDCl3): δ = −62.2. ‒ MS (CI, 100 eV): m/z (%) = 448 (32) [M+2H]+, 447 (100) [M+H]+, 428 (14) [M+H–F]+, 427 (62) [M−F]+. ‒ Analysis calcd. for C24H16F6N2 (446.39): C 64.58, H 3.61, N 6.28; found C 64.32, H 3.73, N 6.38.

4.2.5 3,9-Di-tert-butyl-1,7-bis(trifluoromethyl)quinolino[8,7-h]quinoline (6e)

Prepared from iminium salt 3e (396 mg, 1.12 mmol) and 1,5-diaminonaphthalene (88 mg, 0.56 mmol). The reaction mixture was stirred at room temperature for 15 h. The solvent was evaporated in vacuo and the solid residue was washed with a small volume of cold acetonitrile, then recrystallized from CH2Cl2 to afford the colorless product (218 mg, 0.46 mmol, 82% yield), m.p. 196 °C. ‒ IR (KBr): ν ˜  = 1614 (m), 1586 (m), 1494 (m), 1362 (s), 1298 (m), 1263 (s), 1200 (m), 1163 (s), 1137 (s), 1077 (m), 895 (m), 879 (w), 847 (m), 679 (m) cm−1. ‒ 1H NMR (CDCl3, 400 MHz): δ = 1.62 (s, 18H), 7.98 (s, 2H, 2,8-H), 8.32 (dq, 3 J H,H = 9.3 Hz, 5 J H,F = 2.2 Hz, 2H, 6,12-H), 9.57 (d, 3 J H,H = 9.2 Hz, 2H, 5,11-H). ‒ 13C{1H} NMR (CDCl3, 126 MHz): δ = 30.4 (s), 39.1 (s), 115.8 (q, 3 J C,F = 5.2 Hz), 120.8 (s), 122.0 (q, 4 J C,F = 2.4 Hz), 124.1 (q, 1 J C,F = 275 Hz, CF3), 124.8 (s), 131.9 (s), 134.7 (q, 2 J C,F = 31.2 Hz), 145.5 (s), 168.3 (s); for assignments, see Table 1. ‒ 19F NMR (CDCl3): δ = −62.0. ‒ MS (CI, 100 eV): m/z (%) = 479 (100) [M+H]+, 478 (17) [M]+, 460 (13) [M+H–F]+, 459 (50) [M−F]+. ‒ Analysis calcd. for C26H24F6N2 (478.47): C 65.27, H 5.06, N 5.85; found C 65.12, H 5.00, N 5.89.

4.3 Benzo[h]quinoline 7a and 4,9-bis(trifluoromethyl)quinolino[7,8-h]quinolines 8

4.3.1 1,1,1-Trifluoro-4-phenyl-N-(2-phenyl-4-(trifluoromethyl)benzo[h]quinolin-10-yl)-but-3-yn-2-imine (7a)

In an oven-dried Schlenk flask flushed with argon, a solution of iminium salt 3a (295 mg, 0.79 mmol) in dry acetonitrile (5 mL) was prepared and 1,8-diaminonaphthalene (62 mg, 0.39 mmol) was added, whereupon the solution color changed to orange and brown. After stirring at room temperature during 20 h the voluminous precipitate was separated by filtration and washed with a small amount of cold acetonitrile, then recrystallized from CH2Cl2-n-pentane at 5 °C. A yellow crystalline solid (177 mg, 0.34 mmol, 87% yield), m.p. 107 °C, was obtained. ‒ IR (KBr): ν ˜  = 2199 (w), 1593 (m), 1375 (m), 1354 (m), 1260 (m), 1203 (m), 1166 (s), 1131 (s), 1063 (m), 692 (m) cm−1. ‒ 1H NMR (CDCl3, 500 MHz): δ = 7.09–7.13 (m, 2H), 7.18–7.25 (m, 3H), 7.31 (tt, 3 J H,H = 7.5 Hz, 4 J H,H = 1.2 Hz, 1H), 7.52 (tt, 3 J H,H = 7.3 Hz, 4 J H,H = 1.2 Hz, 1H), 7.58 (tt, 3 J H,H = 7.1 Hz, 4 J H,H = 1.6 Hz, 2H), 7.78 (t, 3 J H,H = 7.7 Hz, 1H), 7.90 (dd, 3 J H,H = 7.9 Hz, 4 J H,H = 1.3 Hz, 1H), 7.98 (d, 3 J H,H = 9.2 Hz, 1H), 8.09 (dq, 3 J H,H = 9.2 Hz, 5 J H,F = 2.1 Hz, 1H), 8.20–8.25 (m, 3H). ‒ 13C{1H} NMR (CDCl3, 126 MHz): δ = 79.6 (s), 99.9 (s), 115.3 (q, 3 J C,F = 5.3 Hz), 118.8 (s), 119.3 (q, 1 J C,F = 277 Hz), 120.0 (s), 121.5 (q, 4 J C,F = 2.8 Hz), 121.8 (s), 122.8 (s), 123.9 (q, 1 J C,F = 275 Hz), 126.8 (s), 128.0 (s, 2C), 128.5 (s, 2C), 128.6 (s), 129.0 (s, 2C), 129.8 (s), 130.0 (s), 130.6 (s), 132.7 (s, 2C), 134.6 (q, 2 J C,F = 31.1 Hz), 135.3 (s), 138.6 (s), 138.8 (q, 2 J C,F = 38.7 Hz), 147.8 (s), 148.1 (s), 156.1 (s). ‒ 19F NMR (CDCl3): δ = −72.2, −61.9. ‒ HRMS ((+)-ESI): m/z = 519.12818 [M+H]+; calcd. for [C30H17F6N2]+: 519.12904. ‒ C30H16F6N2 (518.46 g mol−1).

4.3.2 2,11-Diphenyl-4,9-bis(trifluoromethyl)quinolino[7,8-h]quinoline (8a)

In a Schlenk tube equipped with a magnetic stirring bar and a screw cap and flushed with argon, iminium salt 3a (744 mg, 1.98 mmol) was dissolved in dry acetonitrile (5 mL) and 1,8-diaminonaphthalene (157 mg, 0.99 mmol) was added. The mixture was stirred at room temperature for 1.5 h, during which time a yellow precipitate of 7a (see preceding paragraph) appeared. The temperature was raised to 60 °C and stirring was continued for 36 h. After cooling to 0 °C, the precipitate was filtered off, washed with a small volume of cold acetonitrile, then dissolved in cyclohexane-EtOAc (10:1 v/v) and passed through a short column filled with silica gel 60 (length ∼10 cm, diameter ∼2 cm) to obtain, after solvent evaporation, the major amount of product. Additional product was obtained from the concentrated acetonitrile wash by the same chromatographic procedure. The two batches of product were combined and recrystallized from CH2Cl2-n-pentane at 5 °C. A light yellow crystalline solid (361 mg, 0.69 mmol, 70% yield), m.p. 192 °C, was obtained. Various efforts to remove some impurities, which were indicated by the NMR spectra, were unsuccessful. These impurities were deposited on the crystal surfaces of 8a. ‒ IR (KBr): ν ˜  = 1627 (w), 1606 (w), 1575 (w), 1536 (w), 1372 (m), 1292 (m), 1262 (s), 1154 (s), 1125 (s), 695 (m) cm−1. ‒ 1H NMR (CDCl3, 400 MHz): δ = 7.29–7.35 (m, 4HPh), 7.46 (tt, 3 J H,H = 7.4 Hz, = 1.3 Hz, 2H, HPh), 8.10 (d, 3 J H,H = 8.9 Hz, 2H, 6,7-H), 8.24–8.29 (m, 4H, HPh), 8.34–8.40 (m, 4H, H-5(8), H-3(10)). ‒ 13C{1H} NMR (CDCl3, 126 MHz): δ = 115.4 (q, 3 J C,F = 5.5 Hz, C-3(10)), 122.3 (s), 124.0 (q, 1 J C,F = 275 Hz, CF3), 124.4 (q, 4 J C,F = 2.7 Hz, C5(8)), 128.5 (s, several C), 128.8 (s), 129.0 (s), 129.8 (s), 134.9 (q, 2 J C,F = 31.2 Hz, C4(9)), 135.7 (s, C-6a?), 138.8 (s), 148.2 (s, C12a(12c)), 156.6 (s, C2(11)). ‒ 19F NMR (CDCl3): δ = −61.6. ‒ HRMS (MALDI): m/z = 519.12877 [M+H]+, 518.12104 [M]+; calcd. for [C30H17F6N2]+: 519.12904, [C30H16F6N2]+: 518.12177. ‒ C30H16F6N2 (518.46 g mol−1).

4.3.3 2,11-Di-tert-butyl-4,9-bis(trifluoromethyl)quinolino[7,8-h]quinoline (8b)

The preparation from iminium salt 3e (776 mg, 2.19 mmol) and 1,8-diaminonaphthalene (173 mg, 1.09 mmol) was similar to the synthesis of 8a. However, the reaction mixture was stirred at room temperature for 18 h followed by four days at 40 °C and two days at 60 °C. Precipitation of a solid began at 40 °C. At the end of the reaction, the mixture was cooled at 0 °C, the precipitate was isolated by filtration and washed with a small volume of cold acetonitrile. Additional product was obtained from the mother liquor, which was passed through a column (∼10 × 2 cm) filled with silica gel 60 (elution with cyclohexane-EtOAc (4:1 v/v)). The solvent of the product fraction was evaporated, and the solid residue was recrystallized from acetonitrile-n-pentane at 0 °C. Combined yield of product 8b: 380 mg (0.79 mmol, 73% yield); sand yellow solid, m.p. 128 °C. – IR (KBr): ν ˜  = 1607 (m), 1359 (s), 1262 (s), 1195 (m), 1155 (s), 1126 (s), 1029 (m), 893 (m), 834 (m), 682 (m) cm−1. ‒ 1H NMR (CDCl3, 500 MHz): δ = 1.61 (s, 18H), 7.97 (d, 3 J H,H = 8.9 Hz, 2H, 6,7-H), 7.99 (s, 2H, 3,10-H), 8.27 (dq, 3 J H,H = 8.8 Hz, 5 J H,F = 1.9 Hz, 2H, 5,8-H). ‒ 13C{1H} NMR (CDCl3, 126 MHz): δ = 30.6 (s, CMe 3), 39.2 (s, CMe3), 115.0 (q, 3 J C,F = 5.2 Hz), 121.4 (s, Cq), 123.9 (q, 4 J C,F = 2.5 Hz), 124.2 (q, 1 J C,F = 275 Hz, CF3), 127.6 (s, Cq), 127.9 (s, CH), 134.0 (q, 2 J C,F = 30.9 Hz), 135.2 (s, Cq), 147.3 (s, CH), 168.1 (s, C-2, C-11); for more assignments, see Table 1. ‒ 19F NMR (CDCl3): δ = −61.5. ‒ MS (CI, 100 eV): m/z (%) = 479 (100) [M+H]+, 460 (9) [M+H–F]+, 459 (35) [M−F]+. ‒ Analysis calcd. for C26H24F6N2 (478.48): C 65.27, H 5.06, N 5.85; found C 64.97, H 5.13, N 5.75.

5 Supporting information

The NMR spectra of 6e and 8b are given as supplementary material available online (https://doi.org/10.1515/znb-2021-0099).

Corresponding author: Gerhard Maas, Institute of Organic Chemistry I, Ulm University, Albert-Einstein-Allee 11, D-89081 Ulm, Germany, E-mail:

Funding source: Ulm University

Acknowledgments

We thank Dr. M. Wunderlin for recording the mass spectra.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported financially by Ulm University.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/znb-2021-0099).

Received: 2021-07-19
Accepted: 2021-08-17
Published Online: 2021-09-06
Published in Print: 2021-10-26

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. In this issue
  3. Research Articles
  4. Antimycobacterial cycloartane derivatives from the roots of Trichilia welwistchii C. DC (Meliaceae)
  5. Three metal(II) complexes constructed using the 2-(1H-benzo[d]imidazol-2-yl)quinoline ligand
  6. Low-perchlorate blue-flame pyrotechnic compositions
  7. A convenient synthesis of trifluoromethyl-substituted quinolino[8,7-h]quinolines and quinolino[7,8-h]quinolines
  8. Curie temperature adjustment in the solid solution Gd1–xY x PtMg
  9. Synthesis of oligotetramethylene oxides with terminal amino groups as curing agents for an epoxyurethane oligomer
  10. Synthesis, characterization and optoelectronic properties of 2D hybrid RPbX4 semiconductors based on an isomer mixture of hexanediamine-based dications
  11. Electrochemical sensing of hydrogen peroxide on a carbon paste electrode modified by a silver complex based on the 1,3-bis(1H-benzimidazole-2-yl)propane ligand
https://doi.org/10.1515/znb-2021-0099
Schlagwörter für diesen Artikel
acetylenic iminium salts; cyclocondensation; organofluorine chemistry; quinolino-quinolines; trifluoromethyl-containing building blocks

Artikel in diesem Heft

  1. Frontmatter
  2. In this issue
  3. Research Articles
  4. Antimycobacterial cycloartane derivatives from the roots of Trichilia welwistchii C. DC (Meliaceae)
  5. Three metal(II) complexes constructed using the 2-(1H-benzo[d]imidazol-2-yl)quinoline ligand
  6. Low-perchlorate blue-flame pyrotechnic compositions
  7. A convenient synthesis of trifluoromethyl-substituted quinolino[8,7-h]quinolines and quinolino[7,8-h]quinolines
  8. Curie temperature adjustment in the solid solution Gd1–xY x PtMg
  9. Synthesis of oligotetramethylene oxides with terminal amino groups as curing agents for an epoxyurethane oligomer
  10. Synthesis, characterization and optoelectronic properties of 2D hybrid RPbX4 semiconductors based on an isomer mixture of hexanediamine-based dications
  11. Electrochemical sensing of hydrogen peroxide on a carbon paste electrode modified by a silver complex based on the 1,3-bis(1H-benzimidazole-2-yl)propane ligand
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