Next Article in Journal
Dichloro-μ2,μ2-naphthalene-1,8-diyl-bis(N,N,N′,N′-tetramethylethylenediamino)tetracopper(I)
Previous Article in Journal
(±)-R,S-2-Chloro-N-(4-methyl-2-oxo-2H-chromen-7-yl)-2-phenylacetamide
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molbank
Volume 2024
Issue 2
10.3390/M1831
molbank-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Communication

Introducing Bis(5-(Trifluoromethyl)pyridin-2-yl)amine Chelating Unit via Pd-Catalyzed Amination

by
Nikolay A. Korinskiy
1,
Anton S. Abel
1,*,
Violetta A. Ionova
1,
Stanislav I. Bezzubov
2,
Alexei D. Averin
1 and
Irina P. Beletskaya
1,3
1
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia
2
Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Leninskiy Pr. 31, 119991 Moscow, Russia
3
Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninsky Pr. 31, 119071 Moscow, Russia
*
Author to whom correspondence should be addressed.
Molbank 2024, 2024(2), M1831; https://doi.org/10.3390/M1831
Submission received: 21 April 2024 / Revised: 20 May 2024 / Accepted: 24 May 2024 / Published: 4 June 2024
Browse Figures
Versions Notes

Abstract

:
We report a one-step synthesis of trifluoromethyl-substituted di(pyridin-2-yl)amine-based ligands. N-(hetero)aryl-substituted bis(5-(trifluoromethyl)pyridin-2-yl)amines were obtained from 2-bromo-5-(trifluoromethyl)pyridine and corresponding aromatic amines via Pd-catalyzed amination reaction in the presence of a Pd(dba)2/BINAP catalytic system. Four new ligands were prepared in good to high yields and characterized by NMR, IR spectroscopies and mass spectrometry. The structure of one of the products was additionally supported by X-ray analysis.

1. Introduction

Bis(pyridin-2-yl)amine (dpa) and its derivatives are flexible bidentate N,N-ligands that are widely applied in supramolecular chemistry [1,2,3], catalysis [4,5,6,7] and ion sensing [8,9,10]. Metal complexes of bis(pyridin-2-yl)amine-based ligands demonstrate luminescent properties [11], possess cytotoxic activity and can bind with DNA molecules [12,13,14,15]. Introducing fluorine-containing groups to the molecule’s structure is in demand because of the influence of such moieties on electronic properties, solubility, conformations and the lipophilicity of the compound [16,17,18,19,20]. Synthesis of dpa derivatives can be performed via N-alkylation [1] or N-arylation [2,3] of dpa or by N,N-diarylation of amines with 2-halogenosubtituted pyridine [21,22]. N,N-diarylation of amines with 2-bromopyridine was reported by Buchwald’s group during the first years after the discovery of the Pd-catalyzed amination reaction [23]. This way seems to be the most appropriate for the synthesis of the ligands containing substituents in the pyridine rings [21]. On the other hand, pyridine and other heterocycles can form complexes with palladium and interfere with the reaction, which may require careful optimization of the catalytic system [23,24]. Amination of commercially available 2-bromo-5-(trifluoromethyl)pyridine under Cu-, Ni- and Pd-catalyzed conditions was previously reported [25,26,27,28,29,30], but only a few examples of Pd-catalyzed N,N-diarylation of amines with this substrate are reported. Thus, N,N-diarylation of aliphatic amines is described for two examples [26]. The only example of N,N-diarylation of aromatic amine with 2-bromo-5-(trifluoromethyl)pyridine is described in [31]; this protocol includes the use of a microwave reactor (120 °C), and the yield of the product is only 40%. In the present communication, we report a one-step synthesis of bis(5-(trifluoromethyl)pyridin-2-yl)amino-substituted arenes and heteroarenes from 2-bromo-5-(trifluoromethyl)pyridine via a Pd-catalyzed amination reaction. We consider these fluorine-containing ligands to be of interest for the synthesis of metal complexes and supramolecular structures for various applications.

2. Results and Discussion

Diarylation of p-anisidine 2a with 2-bromo-5-(trifluoromethyl)pyridine 1 was studied as a model reaction (Scheme 1). The reaction was performed under an argon atmosphere in boiling 1,4-dioxane in the presence of sodium tert-butoxide as a base, three equivalents of 1 were taken. The progress of the reaction and the yields of the product were monitored by 1H NMR spectroscopy using internal standard.
We started our investigation from Pd(dba)2/DavePhos (4/4.5 mol%) catalytic system (dba = dibenzylideneacetone, DavePhos = 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl), which was previously reported to be effective for the amination of 2-bromo-5-(trifluoromethyl)pyridine [26]. Full conversion of the amine 2a was observed after 24 h, but the yields of amination products 3a and 4a were quite poor because of numerous side reactions (Table 1, entry 1). The increase in the catalyst loading to 8/9 mol% led to the formation of products 3a and 4a in yields of 32 and 17%, respectively (Table 1, entry 2). Using rac-BINAP ligand (rac-BINAP = rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene) provided an increase in the selectivity of the N,N-diarylation reaction (Table 1, entry 3). The highest yield of the target product 3a (71%) was achieved in the presence of Pd(dba)2/rac-BINAP (8/9 mol%) catalytic system (Table 1, entry 4).
In the next step, we undertook the synthesis of a representative series of bis(5-(trifluoromethyl)pyridin-2-yl)amine-based ligands 3b–d under optimized conditions (Scheme 2). The N-phenyl derivative 3b was obtained in a 71% yield, while quinoline- and 1,10-phenanthroline-based ditopic ligands 3c and 3d were afforded in very good yields (90 and 83%, respectively). The obtained yields are superior to those previously reported for a similar reaction, which gives a 40% yield and proceeds under more stringent conditions (120 microwave reactor, sealed ampoule), which limits its scaling. Thus, the procedure can be applied for the synthesis of various ligands from corresponding amino substituted arenes and heteroarenes.
All the compounds obtained were characterized by NMR and IR spectroscopies and mass spectrometry. The signals in 1H NMR spectra of the products can be easily attributed to the protons in the structure basing on their chemical shifts, coupling constants and relative integral values. A typical 1H NMR spectrum (compound 3c) is shown in Figure 1, and the full spectra of the products are given in the Supplementary Materials.
Three characteristic signals of the double intensity, which correspond to 2-amino-5-(trifluoromethyl)pyridine moiety, are observed in the 1H spectra in all the products (3a–d). The upfield doublet (7.17 ppm, 3J = 8.8 Hz) corresponds to the protons at the ortho-position to the amino group, a doublet of doublets (7.80 ppm, 3J = 8.8 Hz, 4J = 2.4 Hz) corresponds to the protons at position 4 of the pyridine rings, and a downfield broadened multiplet is assigned to the protons at position 6. In the case of 3c, a characteristic doublet of doublets (7.42 ppm, 3J = 8.4 Hz, 3J = 4.3 Hz) was attributed to the proton at position 3 of quinoline, the downfield doublet of doublets (8.93 ppm, 3J = 4.3 Hz, 4J = 1.7 Hz) can be assigned to the proton at position 2 of quinoline, and the downfield doublet of doublets (8.07 ppm, 3J = 8.4 Hz, 4J = 1.7 Hz) corresponds to the proton at position 4. It should be noted that the signals of the protons at positions 5 and 7 (7.54 and 7.67 ppm, 4J = 2.3 Hz) are in a lower field compared to the signals of the corresponding protons in 6-aminoquinoline, which is due to the electron-withdrawing effect of 5-(trifluoromethyl)pyridine moieties. This is also observed in the spectra of other products. The 8.19 ppm doublet (3J = 9.0 Hz) corresponds to the proton at position 8. One can observe characteristic quadruplets in 13C{1H} NMR spectra with (1JCF = 271.4 Hz, 2JCF = 33.6 Hz, 3JCF = 4.1 and 3.1 Hz), which can be attributed to the CF3 group and carbon atoms at positions 5, 6 and 4 of the pyridine core, respectively. The characteristic signals of the CF3 group (–61.9 ppm) are observed in the 19F NMR spectra of the products.
For product 3c, a crystal of satisfactory quality was obtained, and its structure was additionally proved by X-ray analysis (Figure 2a). Product 3c forms crystals of a monoclinic system with P21 symmetry. In the crystal, molecules are assembled by parallel displaced π-π interactions between the quinolinyl moieties (Figure 2b). The resulting stacks passing along the a axis are grafted together by several C-H-π contacts, forming thick layers in the 0ab plane. The layers are packed along the c axis by van der Waals interactions.

3. Materials and Methods

3.1. Apparatus

The 1H, 13C and 19F NMR spectra were registered on a Bruker Avance-400 spectrometer (Bruker Daltonics, Bremen, Germany) in chloroform-d1 using the residual signals of chloroform as internal standard. MALDI-TOF mass spectra were registered on a Bruker Daltonics Autoflex II mass spectrometer (Bruker Daltonics, Bremen, Germany) in positive ion mode with a dithranol matrix and poly(ethyleneglycols) as internal standards. HRMS ESI mass spectrum was obtained on TripleTOF 5600+ mass spectrometer (AB Sciex) (voltage 5.5 kV for positive ions mode ion source gas 15 arb, curtain gas 20 arb; eluent MeCM + 0.1% HCOOH). FTIR spectra were registered on a Nicolet iS 5 (Thermo Fisher Scientific, Waltham, MA, USA) with iD3 ATR accessory (ZnSe). Melting points were obtained using Electrothermal IA 9200 apparatus.

3.2. Reagents

Unless otherwise noted, all chemicals and starting materials were obtained commercially from ABCR (Karlsruhe, Germany) and Sigma-Aldrich (Merck Co., Rahway, NJ, USA) and used without further purification. Pd(dba)2 was synthesized according to a known procedure [32] and used without recrystallization. 5-Amino-1,10-phenanthroline was obtained from 1,10-phenanthroline monohydrate in two steps according to a previously reported method [33]. Preparative column chromatography was carried out using silica gel 60 (40⎼63 µm) from Merck Co. 1,4-Dioxane was distilled successively over NaOH and sodium under argon, CH2Cl2 was distilled over CaH2, and MeOH and petroleum ether were used freshly distilled.

3.3. Synthesis

General procedure. A two-neck flask equipped with a condenser and a magnetic stirrer was charged with 2-bromo-5-(trifluoromethyl)pyridine 1 (170 mg, 0.75 mmol), Pd(dba)2 (12 mg, 8 mol%) and rac-BINAP (14 mg, 9 mol%) and flushed with dry argon. Absolute 1,4-dioxane (2.5 mL) was added in a stream of argon, and the mixture was stirred for 2–3 min. Then, corresponding amine 2a–d (0.25 mmol) and tBuONa (72 mg, 0.75 mmol) were added in a stream of argon, and the mixture was refluxed for 24 h. After cooling to ambient temperature, the reaction mixture was diluted with CH2Cl2 (ca. 10 mL), and the solution was passed through the paper filter and concentrated under reduced pressure. The residue was chromatographed on silica gel using a sequence of eluents: petroleum ether/CH2Cl2 2:1–1:2 v/v, CH2Cl2, CH2Cl2/MeOH 200:1–50:1 (v/v).
N-(4-methoxyphenyl)-5-(trifluoromethyl)-N-(5-(trifluoromethyl)pyridin-2-yl)pyridin-2-amine (3a) was obtained according to a general procedure from 2-bromo-5-(trifluoromethyl)pyridine 1 (169.5 mg, 0.75 mmol), p-anisidine 2a (31 mg, 0.25 mmol) in the presence of Pd(dba)2 (12 mg, 8 mol%), BINAP (14 mg, 9 mol%) and tBuONa (72 mg, 0.75 mmol) in 1,4-dioxane (2.5 mL). Eluent CH2Cl2. Yield 73 mg (71%), yellowish oil. 1H-NMR (400 MHz, CDCl3) δH 3.84 (s, 3H, OCH3), 6.96–7.03 (m, 2H, H2, H6 (Ph)), 7.12 (d, 3J = 8.7 Hz, 2H, H3 (Py)), 7.14–7.19 (m, 2H, H3, H5, (Ph)), 7.75 (dd, 3J = 8.7 Hz, 4J = 2.3 Hz, 2H, H4 (Py)), 8.52–8.55 (m, 2H, H6 (Py)). 13C-NMR (100.6 MHz, CDCl3) δC 55.5 (1C, CH3O), 115.6 (4C, CH (Ph)), 123.4 (q, 1JCF = 271.5 Hz, 2C, CF3), 120.8 (q, 2JCF = 33.3 Hz, 2C, C5 (Py)), 129.7 (2C, C3 (Py)), 134.6 (q, 3JCF = 3.1 Hz, 2C, C4 (Py)), 135.7 (1C, Cquat (Ph)), 145.5 (q, 3JCF = 4.1 Hz, 2C, C6 (Py), 158.8 (1C, Cquat (Ph)), 159.6 (2C, C2 (Py)). 19F-NMR (376.5 MHz, CDCl3) δF –61.86 (6F, CF3). IR (neat): 609 (w), 674 (w), 702 (w), 711 (w), 737 (m), 760 (w), 776 (w), 805 (w), 829 (m), 939 (w), 1010 (m), 1033 (m), 1078 (vs), 1163 (m), 1209 (w), 1244 (s), 1285 (s), 1311 (vs), 1401 (w), 1443 (w), 1466 (w), 1482 (m), 1495 (w), 1510 (m), 1561 (w), 1576 (w), 1600 (m), 1617 (w) cm−1. HRMS (MALDI TOF): m/z [M + H]+ calcd for C19H14F6N3O+: 414.1041; found: 414.1073.
N-phenyl-5-(trifluoromethyl)-N-(5-(trifluoromethyl)pyridin-2-yl)pyridin-2-amine (3b) was obtained according to a general procedure from 2-bromo-5-(trifluoromethyl)pyridine 1 (675 mg, 3 mmol), aniline 2b (93 mg, 92 μL, 1 mmol) in the presence of Pd(dba)2 (46 mg, 8 mol%), BINAP (56 mg, 9 mol%) and tBuONa (288 mg, 3 mmol) in 1,4-dioxane (10 mL). Eluent CH2Cl2. Yield 272 mg (71%), yellowish oil. 1H-NMR (400 MHz, CDCl3) δH 7.13 (d, 3J = 8.8 Hz, 2H, H3 (Py)), 7.21–7.27 (m, 2H, H2, H6 (Ph)), 7.33–7.40 (m, 1H, H4 (Ph)), 7.44–7.52 (m, 2H, H3, H5 (Ph)), 7.78 (d, 3J = 8.8 Hz, 2H, H4 (Py)), 8.56 (br. s, 2H, H6 (Py)). 13C-NMR (100.6 MHz, CDCl3) δC 115.9 (2C, C3 (Py)), 121.0 (q, 2JCF = 33.1 Hz, 2C, C5 (Py)), 123.6 (q, 1JCF = 271.3 Hz, 2C, CF3), 127.9 (1C, C4 (Ph)), 128.2 (2C, C2, C6 (Ph)), 130.3 (2C, C3, C5 (Ph)), 134.7 (q, 3JCF = 3.1 Hz, 2C, C4 (Py)), 143.2 (2C, C1 (Ph)), 145.6 (q, 3JCF = 4.1 Hz, 2C, C6 (Py)), 159.5 (2C, C2 (Py)). 19F-NMR (376.5 MHz, CDCl3) δF –61.9 (6F, CF3). IR (neat): 607 (w), 632 (w), 656 (w), 674 (w), 697 (m), 719 (w), 755 (m), 830 (m), 938 (m), 1010 (m), 1078 (vs), 1114 (vs), 1163 (m), 1207 (w), 1284 (s), 1311 (vs), 1400 (w), 1481 (m), 1491 (m), 1575 (w), 1600 (m), 1617 (w) cm−1. HRMS (MALDI TOF): m/z [M + H]+ calcd for C18H12F6N3+: 384.0935; found: 384.0965.
N,N-bis(5-(trifluoromethyl)pyridin-2-yl)quinolin-6-amine (3c) was obtained according to a general procedure from 2-bromo-5-(trifluoromethyl)pyridine 1 (170 mg, 0.75 mmol), 6-quinolinamine 2c (36 mg, 0.25 mmol) in the presence of Pd(dba)2 (12 mg, 8 mol%), BINAP (14 mg, 9 mol%) and tBuONa (72 mg, 0.75 mmol) in 1,4-dioxane (2.5 mL). Eluent CH2Cl2/MeOH 100:1 (v/v). Yield 98 mg (90%), yellowish crystals. M. p. 180–181 °C. 1H-NMR (400 MHz, CDCl3) δH 7.18 (d, 3J = 8.8 Hz, 2H, H3 (Py)), 7.42 (dd, 3J = 8.4 Hz, 3J = 4.3 Hz, 1H, H3 (Quin)), 7.54 (dd, 3J = 9.0 Hz, 4J = 2.4 Hz, 1H, H7 (Quin)), 7.67 (d, 4J = 2.4 Hz, 1H, H5 (Quin)), 7.80 (dd, 3J = 8.8 Hz, 4J = 2.3 Hz, 2H, H4 (Py)), 8.07 (dd, 3J = 8.4 Hz, 4J = 1.7 Hz, 1H, H4 (Quin)), 8.19 (d, 3J = 9.0 Hz, 1H, H8 (Quin)), 8.56 (q, 4JHF = 0.8 Hz, 2H, H6 (Py)), 8.93 (dd, 3J = 4.3, 4J = 1.7 Hz, 1H, H2(Quin)). 13C-NMR (100.6 MHz, CDCl3) δC 116.1 (2C, C3 (Py)), 123.6 (q, 1JCF = 271.4 Hz, 2C, CF3), 121.5 (q, 2JCF = 33.6 Hz, 2C, C5 (Py)), 121.8 (1C, CH (Quin)), 125.9 (1C, CH (Quin)), 129.1 (1C, Cquat (Quin)), 129.8 (1C, CH (Quin)), 131.9 (1C, CH (Quin)), 134.9 (q, 3JCF = 3.1 Hz, 2C, C4 (Py)), 135.8 (1C, CH (Quin)), 141.3(1C, Cquat (Quin)), 145.8 (q, 3JCF = 4.1 Hz, 2C, C6 (Py)), 147.0 (1C, Cquat (Quin)), 150.9 (1C, C2 (Quin)), 159.4 (2C, C2 (Py)). 19F-NMR (376.5 MHz, CDCl3) δF –61.9 (6F, CF3). IR (neat): 609 (w), 620 (w), 644 (w), 669 (w), 698 (m), 736 (s), 761 (m), 780 (w), 796 (m), 830 (m), 836 (m), 889 (w), 940 (w), 969 (w), 982 (w), 1010 (m), 1031 (w), 1078 (vs), 1115 (s), 1165 (m), 1263 (s), 1277 (m), 1287 (m), 1314 (s), 1326 (s), 1375 (w), 1400 (w), 1437 (w), 1464 (w), 1484 (m), 1492 (m), 1575 (w), 1599 (m) cm−1. HRMS (MALDI TOF): m/z [M + H]+ calcd for C21H13F6N4+: 435.1044; found: 435.1089.
N,N-bis(5-(trifluoromethyl)pyridin-2-yl)-1,10-phenanthrolin-5-amine (3d) was obtained according to a general procedure from 2-bromo-5-(trifluoromethyl)pyridine 1 (170 mg, 0.75 mmol), 1,10-phenanthrolin-5-amine 2d (61 mg, 0.25 mmol) in the presence of Pd(dba)2 (12 mg, 8 mol%), BINAP (14 mg, 9 mol%) and tBuONa (72 mg, 0.75 mmol) in 1,4-dioxane (2.5 mL). Eluent CH2Cl2/MeOH 100:1 (v/v). Yield 101 mg (83%), beige crystals. M. p. 245–246 °C. 1H-NMR (400 MHz, CDCl3) δH 7.21 (d, 3J = 8.8 Hz, 2H, H3 (Py)), 7.52 (dd, 3J = 8.3 Hz, 3J = 4.3 Hz, 1H, H3 (Phen)), 7.63 (dd, 3J = 8.1 Hz, 4J = 4.4 Hz, 1H, H8 (Phen)), 7.75 (dd, 3J = 8.8 Hz, 4J = 2.4 Hz, 2H, H4 (Py)), 7.79 (s, 1H, H6 (Phen)), 8.06 (dd, 3J = 8.3 Hz, 4J = 1.6 Hz, 1H, H4 (Phen)), 8.19 (dd, 3J = 8.1 Hz, 4J = 1.6 Hz, 1H, H7 (Phen)), 8.47–8.49 (m, 2H, H6 (Py)), 9.18 (dd, 3J = 4.3 Hz, 4J = 1.6 Hz, 1H, H2 (Phen)), 9.21 (dd, 3J = 4.3 Hz, 4J = 1.6 Hz, 1H, H9 (Phen)). 13C-NMR (100.6 MHz, CDCl3) δC 114.9 (2C, C3 (Py)), 121.3 (q, 2JCF = 33.5 Hz, 2C, C5 (Py)), 123.3 (q, 1JCF = 271.5 Hz, 2C, CF3), 123.4 (1C, CH), 123.6 (1C, CH), 127.0 (1C, Cquat (Phen)), 127.8 (1C, CH), 128.3 (1C, Cquat (Phen)), 131.8 (1C, CH), 135.0 (q, 3JCF = 3.1 Hz, 2C, C4 (Py)), 136.1 (1C, CH), 137.7 (1C, Cquat (Phen)), 145.6 (q, 3JCF = 4.1 Hz, 2C, C6 (Py)), 146.0 (1C, Cquat (Phen)), 147.6 (1C, Cquat (Phen)), 150.8 (1C, CH), 151.1 (1C, CH), 158.8 (2C, C2 (Py)). 19F-NMR (376.5 MHz, CDCl3) δF –61.9 (6F, CF3). IR (neat): 604 (w), 616 (w), 623 (m), 633 (w), 646 (w), 661 (w), 672 (w), 682 (w), 693 (w), 699 (w), 712 (w), 728 (w), 742 (m), 759 (w), 798 (m), 808 (m), 828 (m), 853 (m), 885 (w), 914 (w), 941 (m), 964 (w), 982 (w), 1007 (m), 1076 (vs), 1116 (vs), 1153 (m), 1166 (m), 1177 (m), 1259 (m), 1284 (s), 1316 (vs), 1385 (w), 1402 (w), 1419 (w), 1479 (m), 1494 (w), 1566 (w), 1578 (w), 1597 (m), 1613 (w) cm–1. HRMS (ESI): m/z [M + H]+ calcd for C24H14F6N5+: 486.1153; found: 486.1143.

3.4. X-ray Analysis of 3c

Clear yellow needle-shaped single crystals of 3c were obtained by slow evaporation of the dichloromethane solution at room temperature. Crystallographic data were collected at 120 K on a Bruker SMART APEX II diffractometer equipped with a PHOTON II CMOS detector using graphite monochromatized Mo–Kα radiation (λ = 0.71073 Å) using a ω-scan mode. Absorption correction based on the measurements of equivalent reflections was applied [34,35]. The structure was solved by direct methods and refined by full-matrix least-squares on F2 with anisotropic thermal parameters for all non-hydrogen atoms using Olex2 package [36]. Hydrogen atoms were placed in calculated positions and refined using a riding model. Crystallographic details are presented in Table S1. CCDC 2347783 contains the supplementary crystallographic data for the structure. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

4. Conclusions

A series of bis(5-(trifluoromethyl)pyridin-2-yl)amine-based ligands containing aryl and heteroaryl N-substituents were synthesized and characterized. The aryl- and heteroaryl derivatives were obtained in one step from 2-bromo-5-(trifluoromethyl)pyridine via Pd-catalyzed amination with corresponding (hetero)arylamines in the presence of Pd(dba)2/BINAP catalytic system in yields up to 90%.

Supplementary Materials

The following supporting information can be downloaded online. Table S1: Details of the X-ray crystal data collection and structure refinement for compound 3c; Figure S1: 1H NMR spectrum of the compound 3a; Figure S2: 13C{1H} NMR spectrum of the compound 3a; Figure S3: 19F{1H} NMR spectrum of the compound 3a; Figure S4: 1H NMR spectrum of the compound 3b; Figure S5: 13C{1H} NMR spectrum of the compound 3b; Figure S6: 19F{1H} NMR spectrum of the compound 3b; Figure S7: 1H NMR spectrum of the compound 3c; Figure S8: 13C{1H} NMR spectrum of the compound 3c; Figure S9: 19F{1H} NMR spectrum of the compound 3c; Figure S10: 1H NMR spectrum of the compound 3d; Figure S11: 13C{1H} NMR spectrum of the compound 3d; Figure S12: 19F{1H} NMR spectrum of the compound 3d.

Author Contributions

Conceptualization, A.S.A. and V.A.I.; methodology, A.D.A.; investigation, N.A.K., A.D.A. and S.I.B.; visualization, A.S.A. and S.I.B.; supervision, A.S.A. and I.P.B.; funding acquisition, A.S.A. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the Russian Science Foundation (grant no. 22-73-00031).

Data Availability Statement

The data presented in this work are available in this article and the Supplementary Materials.

Acknowledgments

I.M. Vatsouro is warmly acknowledged for providing 19F NMR spectra. X-ray experiments were conducted in the Center for Shared Equipment of IGIC RAS.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Bray, D.J.; Clegg, J.K.; Jolliffe, K.A.; Lindoy, L.F. Cobalt(ii), iron(ii), zinc(ii) and palladium(ii) complexes of di-topic 4’-{4-[bis(2-pyridyl)aminomethyl]phenyl}-2,2′:6′,2”-terpyridine. Synthetic and X-ray structural studies. CrystEngComm 2014, 16, 6476–6482. [Google Scholar] [CrossRef]
  2. Pang, J.; Tao, Y.; Freiberg, S.; Yang, X.-P.; D’Iorio, M.; Wang, S. Syntheses, structures, and electroluminescence of new blue luminescent star-shaped compounds based on 1,3,5-triazine and 1,3,5-trisubstituted benzene. J. Mater. Chem. 2002, 12, 206–212. [Google Scholar] [CrossRef]
  3. Sumby, C.J.; Steel, P.J. Coordination chemistry of di-2-pyridylamine-based bridging heterocyclic ligands: A structural study of coordination polymers and discrete dinuclear complexes. Inorg. Chim. Acta 2007, 360, 2100–2114. [Google Scholar] [CrossRef]
  4. Cheung, K.-C.; Guo, P.; So, M.-H.; Lee, L.Y.S.; Ho, K.-P.; Wong, W.-L.; Lee, K.-H.; Wong, W.-T.; Zhou, Z.-Y.; Wong, K.-Y. Electrocatalytic reduction of carbon dioxide by a polymeric film of rhenium tricarbonyl dipyridylamine. J. Organomet. Chem. 2009, 694, 2842–2845. [Google Scholar] [CrossRef]
  5. Cheung, K.-C.; Wong, W.-L.; So, M.-H.; Zhou, Z.-Y.; Yan, S.-C.; Wong, K.-Y. A dinuclear ruthenium catalyst with a confined cavity: Selectivity in the addition of aliphatic carboxylic acids to phenylacetylene. Chem. Commun. 2013, 49, 710–712. [Google Scholar] [CrossRef] [PubMed]
  6. Schnidrig, S.; Bachmann, C.; Müller, P.; Weder, N.; Spingler, B.; Joliat-Wick, E.; Mosberger, M.; Windisch, J.; Alberto, R.; Probst, B. Structure–Activity and Stability Relationships for Cobalt Polypyridyl-Based Hydrogen-Evolving Catalysts in Water. ChemSusChem 2017, 10, 4570–4580. [Google Scholar] [CrossRef] [PubMed]
  7. Zhong, H.; Wang, J.; Li, L.; Wang, R. The copper-free Sonogashira cross-coupling reaction promoted by palladium complexes of nitrogen-containing chelating ligands in neat water at room temperature. Dalton Trans. 2014, 43, 2098–2103. [Google Scholar] [CrossRef] [PubMed]
  8. Kursunlu, A.N.; Şahin, E.; Güler, E. Bodipy/dipyridylamino-based “turn-on” fluorescent chemosensor for trivalent chromium cations: Characterization and photophysical properties. RSC Adv. 2015, 5, 5951–5957. [Google Scholar] [CrossRef]
  9. Weng, Y.-Q.; Teng, Y.-L.; Yue, F.; Zhong, Y.-R.; Ye, B.-H. A new selective fluorescent chemosensor for Cu(II) ion based on zinc porphyrin-dipyridylamino. Inorg. Chem. Commun. 2007, 10, 443–446. [Google Scholar] [CrossRef]
  10. Xie, Y.; Ding, Y.; Li, X.; Wang, C.; Hill, J.P.; Ariga, K.; Zhang, W.; Zhu, W. Selective, sensitive and reversible “turn-on” fluorescent cyanide probes based on 2,2’-dipyridylaminoanthracene–Cu2+ ensembles. Chem. Commun. 2012, 48, 11513–11515. [Google Scholar] [CrossRef]
  11. Ni, J.; Wei, K.-J.; Min, Y.; Chen, Y.; Zhan, S.; Li, D.; Liu, Y. Copper(i) coordination polymers of 2,2’-dipyridylamine derivatives: Syntheses, structures, and luminescence. Dalton Trans. 2012, 41, 5280–5293. [Google Scholar] [CrossRef]
  12. Chitrapriya, N.; Shin, J.H.; Hwang, I.H.; Kim, Y.; Kim, C.; Kim, S.K. Synthesis, DNA binding profile and DNA cleavage pathway of divalent metal complexes. RSC Adv. 2015, 5, 68067–68075. [Google Scholar] [CrossRef]
  13. Ghebreyessus, K.; Peralta, A.; Katdare, M.; Prabhakaran, K.; Paranawithana, S. Ruthenium(II)-arene complexes with naphthalimide-tagged N,O- and N,N-chelating ligands: Synthesis and biological evaluation. Inorg. Chim. Acta 2015, 434, 239–251. [Google Scholar] [CrossRef]
  14. Kinunda, G.; Jaganyi, D. Kinetic and mechanistic studies of cisplatin analogues bearing 2,2′-dipyridylalkylamine ligands. Transition Met. Chem. 2016, 41, 235–248. [Google Scholar] [CrossRef]
  15. Rauterkus, M.J.; Fakih, S.; Mock, C.; Puscasu, I.; Krebs, B. Cisplatin analogues with 2,2′-dipyridylamine ligands and their reactions with DNA model nucleobases. Inorg. Chim. Acta 2003, 350, 355–365. [Google Scholar] [CrossRef]
  16. Abula, A.; Xu, Z.; Zhu, Z.; Peng, C.; Chen, Z.; Zhu, W.; Aisa, H.A. Substitution Effect of the Trifluoromethyl Group on the Bioactivity in Medicinal Chemistry: Statistical Analysis and Energy Calculations. J. Chem. Inform. Model. 2020, 60, 6242–6250. [Google Scholar] [CrossRef] [PubMed]
  17. Li, H.; Li, J.; Liu, D.; Huang, T.; Li, D. Effects of Electron Affinity and Steric Hindrance of the Trifluoromethyl Group on the π-Bridge in Designing Blue Thermally Activated Delayed Fluorescence Emitters. Chem. Eur. J. 2020, 26, 6899–6909. [Google Scholar] [CrossRef]
  18. Yuan, W.; Jin, G.; Su, N.; Hu, D.; Shi, W.; Zheng, Y.-X.; Tao, Y. The electron inductive effect of dual non-conjugated trifluoromethyl acceptors for highly efficient thermally activated delayed fluorescence OLEDs. Dye. Pigment. 2020, 183, 108705. [Google Scholar] [CrossRef]
  19. Glyn, R.J.; Pattison, G. Effects of Replacing Oxygenated Functionality with Fluorine on Lipophilicity. J. Med. Chem. 2021, 64, 10246–10259. [Google Scholar] [CrossRef]
  20. Lezama, J.O.G.; Robles, N.L. Analysis of the effects of trifluoromethyl group on the conformational properties of meta substituted thioacetanilide. J. Mol. Struct. 2021, 1236, 130259. [Google Scholar] [CrossRef]
  21. Abel, A.S.; Averin, A.D.; Buryak, A.K.; Savelyev, E.N.; Orlinson, B.S.; Novakov, I.A.; Beletskaya, I.P. The Palladium-Catalyzed Heteroarylation of Adamantylalkyl Amines with Dihalogenopyridines: Scope and Limitations. Synthesis 2017, 49, 5067–5080. [Google Scholar] [CrossRef]
  22. Kharlamova, A.D.; Abel, A.S.; Averin, A.D.; Beletskaya, I.P. N,N-Di(pyridin-2-yl)quinolin-6-amine: Synthesis and coordination properties. Russ. Chem. Bull. 2019, 68, 597–600. [Google Scholar] [CrossRef]
  23. Wagaw, S.; Buchwald, S.L. The Synthesis of Aminopyridines: A Method Employing Palladium-Catalyzed Carbon-Nitrogen Bond Formation. J. Org. Chem. 1996, 61, 7240–7241. [Google Scholar] [CrossRef] [PubMed]
  24. Shen, Q.; Ogata, T.; Hartwig, J.F. Highly Reactive, General and Long-Lived Catalysts for Palladium-Catalyzed Amination of Heteroaryl and Aryl Chlorides, Bromides, and Iodides: Scope and Structure–Activity Relationships. J. Am. Chem. Soc. 2008, 130, 6586–6596. [Google Scholar] [CrossRef] [PubMed]
  25. Liang, D.; He, Y.; Liu, L.; Zhu, Q. A Metal-Free Tandem Demethylenation/C(sp2)–H Cycloamination Process of N-Benzyl-2-aminopyridines via C–C and C–N Bond Cleavage. Org. Lett. 2013, 15, 3476–3479. [Google Scholar] [CrossRef] [PubMed]
  26. Lyakhovich, M.S.; Murashkina, A.V.; Panchenko, S.P.; Averin, A.D.; Abel, A.S.; Maloshitskaya, O.A.; Savelyev, E.N.; Orlinson, B.S.; Novakov, I.A.; Beletskaya, I.P. Arylation of Adamantanamines: XI. Comparison of the Catalytic Efficiency of Palladium and Copper Complexes in Reactions of Adamantanamines with Fluorinated 2-Bromopyridines. Russ. J. Org. Chem. 2021, 57, 768–783. [Google Scholar] [CrossRef]
  27. Duan, J.; Choy, P.Y.; Gan, K.B.; Kwong, F.Y. N-Difluoromethylation of N-pyridyl-substituted anilines with ethyl bromodifluoroacetate. Org. Biomol. Chem. 2022, 20, 1883–1887. [Google Scholar] [CrossRef] [PubMed]
  28. Liang, Q.; Qiao, Z.; Zhou, Q.; Xue, D.; Wang, K.; Shao, L. Discovery of Potent and Selective Transient Receptor Potential Vanilloid 1 (TRPV1) Agonists with Analgesic Effects In Vivo Based on the Functional Conversion Induced by Altering the Orientation of the Indazole Core. J. Med. Chem. 2022, 65, 11658–11678. [Google Scholar] [CrossRef] [PubMed]
  29. Song, G.; Nong, D.-Z.; Li, J.-S.; Li, G.; Zhang, W.; Cao, R.; Wang, C.; Xiao, J.; Xue, D. General Method for the Amination of Aryl Halides with Primary and Secondary Alkyl Amines via Nickel Photocatalysis. J. Org. Chem. 2022, 87, 10285–10297. [Google Scholar] [CrossRef]
  30. Wu, G.; Xu, X.; Wang, S.; Chen, L.; Pang, B.; Ma, T.; Ji, Y. Metal-free directed C–H borylation of 2-(N-methylanilino)-5-fluoropyridines and 2-benzyl-5-fluoropyridines. Chin. Chem. Lett. 2022, 33, 2005–2008. [Google Scholar] [CrossRef]
  31. Alexander, R.P.; Aujla, P.S.; Crepy, K.V.L.; Foley, A.M.; Franklin, R.J.; Haughan, A.F.; Horsley, H.T.; Jones, W.M.; Lallemand, B.I.L.F.; Mack, S.R.; et al. Fused Thiazole Derivatives as PI3 Kinase Inhibitors and Their Preparation, Pharmaceutical Compositions and Use in the Treatment of Diseases. WO2008001076, 3 January 2008. [Google Scholar]
  32. Ukai, T.; Kawazura, H.; Ishii, Y.; Bonnet, J.J.; Ibers, J.A. Chemistry of dibenzylideneacetone-palladium(0) complexes. J. Organomet. Chem. 1974, 65, 253–266. [Google Scholar] [CrossRef]
  33. Li, H.-H.; Wu, J.-X.; Dong, H.-J.; Wu, Y.-L.; Chen, Z.-R. A combined experimental and theoretical study of an semi-conductive iodoargentate hybrid induced by large conjugate cation. J. Mol. Struct. 2011, 987, 180–185. [Google Scholar] [CrossRef]
  34. Sheldrick, G. Crystal structure refinement with SHELXL. Acta Crystallogr. Sect. C 2015, 71, 3–8. [Google Scholar] [CrossRef] [PubMed]
  35. Sheldrick, G. SHELXT—Integrated space-group and crystal-structure determination. Acta Crystallogr. Sect. A 2015, 71, 3–8. [Google Scholar] [CrossRef]
  36. Dolomanov, O.V.; Bourhis, L.J.; Gildea, R.J.; Howard, J.A.K.; Puschmann, H. OLEX2: A complete structure solution, refinement and analysis program. J. Appl. Crystallogr. 2009, 42, 339–341. [Google Scholar] [CrossRef]
Molbank 2024 m1831 sch001
Scheme 1. Pd-catalyzed amination of 2-bromo-5-(trifluoromethyl)pyridine with p-anisidine.
Scheme 1. Pd-catalyzed amination of 2-bromo-5-(trifluoromethyl)pyridine with p-anisidine.
Molbank 2024 m1831 sch001
Molbank 2024 m1831 sch002
Scheme 2. Pd-catalyzed synthesis of the compounds 3a–d.
Scheme 2. Pd-catalyzed synthesis of the compounds 3a–d.
Molbank 2024 m1831 sch002
Molbank 2024 m1831 g001
Figure 1. 1H NMR spectrum of 3c (400 MHz, CDCl3), aromatic region.
Figure 1. 1H NMR spectrum of 3c (400 MHz, CDCl3), aromatic region.
Molbank 2024 m1831 g001
Molbank 2024 m1831 g002
Figure 2. (a) X-ray structure of 3c; ellipsoids correspond to the 50% probability level. (b) Fragment of the crystal packing of 3c.
Figure 2. (a) X-ray structure of 3c; ellipsoids correspond to the 50% probability level. (b) Fragment of the crystal packing of 3c.
Molbank 2024 m1831 g002
Table 1. Optimization of the reaction conditions.
Table 1. Optimization of the reaction conditions.
Entry 1LigandPd(dba)2/L Loading, mol%Yield of 3a, % 2Yield of 4a, % 2
1DavePhos 34/4.567
2DavePhos 38/93217
3rac-BINAP 44/4.556 512
4rac-BINAP 48/971 57
1 Reaction conditions: 2-bromo-5-(trifluoromethyl)pyridine (170 mg, 0.75 mmol), p-anisidine (31 mg, 0.25 mmol), Pd(dba)2 (4–8 mol%), ligand (4.5–9 mol%), tBuONa (72 mg, 0.75 mmol), 1,4-dioxane, argon atmosphere, reflux, 24 h. 2 Yields were determined by 1H NMR analysis of the reaction mixture using 1,4-phenylene diacetate as internal standard. 3 2-Dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl. 4 2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl. 5 Preparative yield after column chromatography.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Korinskiy, N.A.; Abel, A.S.; Ionova, V.A.; Bezzubov, S.I.; Averin, A.D.; Beletskaya, I.P. Introducing Bis(5-(Trifluoromethyl)pyridin-2-yl)amine Chelating Unit via Pd-Catalyzed Amination. Molbank 2024, 2024, M1831. https://doi.org/10.3390/M1831

AMA Style

Korinskiy NA, Abel AS, Ionova VA, Bezzubov SI, Averin AD, Beletskaya IP. Introducing Bis(5-(Trifluoromethyl)pyridin-2-yl)amine Chelating Unit via Pd-Catalyzed Amination. Molbank. 2024; 2024(2):M1831. https://doi.org/10.3390/M1831

Chicago/Turabian Style

Korinskiy, Nikolay A., Anton S. Abel, Violetta A. Ionova, Stanislav I. Bezzubov, Alexei D. Averin, and Irina P. Beletskaya. 2024. "Introducing Bis(5-(Trifluoromethyl)pyridin-2-yl)amine Chelating Unit via Pd-Catalyzed Amination" Molbank 2024, no. 2: M1831. https://doi.org/10.3390/M1831

APA Style

Korinskiy, N. A., Abel, A. S., Ionova, V. A., Bezzubov, S. I., Averin, A. D., & Beletskaya, I. P. (2024). Introducing Bis(5-(Trifluoromethyl)pyridin-2-yl)amine Chelating Unit via Pd-Catalyzed Amination. Molbank, 2024(2), M1831. https://doi.org/10.3390/M1831

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop