Synthesis and Photophysical Properties of 5-N-Arylamino-4

5-N-Arylamino-4-methylthiazoles were synthesized from commercially available 4-methylthiazole in three consecutive steps: (i) direct Pd-catalyzed C–...
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Synthesis and Photophysical Properties of 5‑N‑Arylamino-4methylthiazoles Obtained from Direct C−H Arylations and Buchwald−Hartwig Aminations of 4‑Methylthiazole Toshiaki Murai,*,† Kirara Yamaguchi,† Teppei Hayano,† Toshifumi Maruyama,† Koji Kawai,‡ Hayato Kawakami,‡ and Akira Yashita‡ †

Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193, Japan Miyoshi Oil & Fat Co., Ltd., 4-66-1 Horikiri, Katsushika-Ku, Tokyo 124-8510, Japan

‡

S Supporting Information *

ABSTRACT: 5-N-Arylamino-4-methylthiazoles were synthesized from commercially available 4-methylthiazole in three consecutive steps: (i) direct Pd-catalyzed C−H arylations of the thiazole, (ii) bromination, and (iii) Pd-catalyzed Buchwald− Hartwig aminations. The resulting thiazoles showed the longest-wavelength absorption maxima at 338−432 nm, and luminescence was observed at 455−726 nm, whereby the latter depends predominantly on the substituents at the 2-position of the thiazole core. The introduction of electron-accepting groups, in particular a nitro group, induced substantial bathochromic shifts of the fluorescence. Thiazoles containing a 3,5-bis(trifluoromethyl)phenyl group at the 2-position exhibited purple to blue emission in the solid state. The energy levels of the frontier molecular orbitals and the Kohn−Sham plots of the 5-N-arylamino-4-methylthiazoles were obtained from DFT calculations at the B3LYP/6-31+G(d,p) level of theory.

1. INTRODUCTION The importance of thiazoles is growing in the context of monocyclic fluorescent molecules,1 as their photophysical properties are sensitive to the introduction of substituents and external stimuli on account of their structural flexibility. In particular, the introduction of electron-donating groups to the carbon atom at the 5-position of thiazoles can lead to typical donor−acceptor (D-A) systems.2 Therefore, a range of derivatives with oxygen-containing3 functional groups at that position has been developed, and their effect on the photophysical properties has been examined. Recently, we have reported the synthesis of 5-N-arylamino-2,4-diarylthiazoles from the reaction of secondary thioamides and thioformamides.4 Even though the alignment in these thiazoles between the electron-donating arylamino and thiazole cores deviates substantially from coplanarity, relatively strong fluorescence was observed. The introduction of electron-accepting groups at the 2-positions shifts the absorption and emission spectra to longer wavelengths. We then investigated the effect of the substituents at the 4-position on the photophysical properties. However, our previous synthetic methods did not allow the introduction of aliphatic groups at that position.4a,b Herein, we report a three-step synthesis of 5-amino-4-methylthiazoles via (i) transition-metal-catalyzed direct C−H arylation, (ii) bromination, and (iii) Buchwald−Hartwig amination (Figure 1), together with the examination of the photophysical properties of the resulting thiazoles. A thiazole that contains a strongly electron accepting nitro group at the 2-position of the thiazole core showed large solvatochromism of its fluorescence. © XXXX American Chemical Society

Figure 1. Synthetic strategy to 5-amino-4-methylthiazoles.

2. RESULTS AND DISCUSSION For the direct C−H arylation of 1 at the 2-position of the thiazole core with aryl iodides, we initially chose, from several known catalysts,5 a system based on a catalytic amount of Pd(OAc)2 and a stoichiometric amount of copper iodide (Figure 2).5b,e The arylation occurred selectively at the 2-position of the thiazole ring of 1 to afford 2-aryl-4methylthiazoles 2 in moderate to good yields. In the reaction of 2e, we also observed the formation of the product derived from the homocoupling of 1a. The subsequent selective bromination was then achieved by treating 2 with bromine in Special Issue: Tailoring the Optoelectronic Properties of Organometallic Compounds with Main Group Elements Received: February 20, 2017

A

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Organometallics Table 1. Buchwald−Hartwig Amination of 3a

Figure 2. Direct C−H arylation of 1.

acetic acid,6 which led to the generation of 2-aryl-5-bromo-4methylthiazoles 3 (Figure 3).

Figure 3. Selective bromination of 2.

Finally, we subjected 3 to Buchwald−Hartwig amination conditions,7 even though precedents of the C-5 amination of thiazoles with N-arylamines have not yet been reported. After several disappointing results, the use of 4,5-bis(diphenylphosphino)9,9-dimethylxanthene (XantPhos) (Table 1) as a ligand in combination with Pd2(dba)38 successfully promoted the amination of 3 to furnish the desired products (4), although the yields depended strongly on the substituents on the aryl groups at the 2-position (Table 1). As amine components, we used N-methylaniline (6a), diphenylamine (6b), and bis(4methoxyphenyl)amine (6c). All new compounds were characterized by 1H and 13C NMR and IR spectroscopy as well as mass spectrometry. The connectivity of 4d was supported by a X-ray diffraction study9 (Figure S1 in the Supporting Information). In order to examine the effect of the nitrogen-containing substituent on the aryl group at the 2-position of the thiazole on the spectroscopic properties, the nitro group in 4d was reduced under hydrogenation conditions to furnish 2-(4-amino)5-aminothiazole 7 in high yield (Figure 4).10 The photophysical properties of the obtained 5-amino-4methylthiazoles are summarized in Table 2. Similarly to our previous 5-aminothiazoles,4c the substituents on the nitrogen atom at the 5-position and on the carbon atom at the 2-position strongly affected the absorption spectra. It should be noted that the photophysical properties of 4ab and those of previously reported thiazole 8 were almost identical. Consequently, the replacement of the phenyl group at the 4-position with a methyl group did not affect the photophysical properties.

a

Thiazole 3 reacted with amine 6 (3 equiv) in an appropriate solvent with Pd2(dba)3 (10 mol %), Xantphos (20 mol %), and Cs2CO3 (2 equiv).

Figure 4. Hydrogenation of 4d.

The longest wavelength absorption of thiazole 4aa was observed at 338 nm. The replacement of the methyl group on the nitrogen atom with aryl groups (e.g., 4ab) bathochromically shifted the maximum absorption to longer wavelengths. Further bathochromic shifts were achieved by introducing electron-accepting groups to the aromatic ring at the 2-position. For example, the maximum absorption of 4d, containing a nitro group, shifted to 432 nm,11 whereas the reduction of the nitro group to an amino group (5d) induced a hypsochromic shift (Δλ = 80 nm). Luminescence spectra were also dominated by the substituents at the 2- and 5-positions, whereby electron-accepting B

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Organometallics Table 2. Photophysical Properties of 4, 7, and 8

Table 3. Photophysical Properties of 2c, 3c, and 4ca in the Solid State

a Measured with a UV-4100 instrument. bMeasured with an FP8500 instrument. cPhotographs of the corresponding solid under illumination with UV light (λex 365 nm).

Table 4. Solvatochromism of Thiazole 4d

[solute] = 1 × 10−5 M. bMeasured with a UV-4100 instrument. Measured with an FP8500 instrument. dPhotographs of a solution of 4d under ilumination with UV light (λex 365 nm).

a c

ln CHCl3, [solute] = 1 × 10−5 M. bMeasured with a UV-4100 instrument. cMeasured with an FP8500 instrument. dExcited at the wavelength of the maximum absorption. eAbsolute fluorescence quantum yield. fSee ref 4c. a

The structures of 4ab, 4b, and 4d were also investigated computationally, using density functional theory (DFT) calculations at the B3LYP/6-31+G(d,p) level of theory.13 The substituents at the 2-positions of these compounds are aligned in an almost coplanar fashion with the thiazole rings (Table 5). In contrast, the alignment of the 5-N-diphenylamino groups significantly deviates from coplanarity with the thiazole rings (dihedral angles: 56.1−61.0°). The HOMOs of 4ab, 4b, and 4d are mainly localized on the 5-N-diphenylamino groups and the thiazole rings, whereas the LUMOs are located on the aryl groups at the 2-positions and the thiazole rings (Figure 5). In particular, the LUMO of 4d is more delocalized on the nitrophenyl group at the 2-position in comparison to the phenyl group of 4ab. These results suggest that the HOMOs and LUMOs of 4ab, 4b, and 4d are not delocalized over the substituents at the 4-positions. Thus, substituents attached at these positions do not exert any influence on the photophysical properties. Accordingly, a correction is required for the long-range interactions. For that purpose, we

groups bathochromically shifted the emission. The presence of the nitro group induced a large Stokes shift (more than 9000 cm−1), and the emission was observed at λem 726 nm, although the quantum yield was low (ΦF = 0.05). In addition to the photophysical properties shown in Table 2, we found that thiazoles 2c, 3c, and 4ca, which contain a 3,5-bis(trifluoromethyl)phenyl group on the aromatic ring at the 2-poisition, exhibited solid-state fluorescence (Table 3). The introduction of bromine at the 5-position induced a hypsochromic shift, whereas that of a diphenylamino group induced a bathochromic shift. Furthermore, 4d exhibited strong solvatochromism of its fluorescence (Table 4). While the absorption wavelengths of 4d in three solvents with different ET(30) values12 were nearly identical, the emission varied from 507 nm (hexane) to 631 nm (THF) and 726 nm (CHCl3) with large Stokes shifts. C

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are in accordance with the experimental results. The introduction of electron-accepting groups (NO2 and CF3) to the phenyl group at the 2-position led to a significant decrease in the LUMOs. Excitation energies of 3.76 eV (4ab), 3.59 eV (4b), and 3.26 eV (4d) were calculated, and these values are consistent with the bathochromic shifts of the absorption bands. To disclose the change in the absorption and emission spectra of Lewis basic thiazole 7 by interaction with a Lewis acid, one of Lewis acids, BF3·Et2O was added to an Et2O solution of 7 (Figure 6 and Figure S2 in the Supporting Information).14

Table 5. Dihedral Angles in 4ab, 4b, and 4d

Figure 6. UV/vis absorption spectroscopic titration of thiazole 7 with BF3·Et2O in Et2O ([7] = 1 × 10−5 M). Legend: (a) equivalents of BF3 are shown.

The addition of a large excess of BF3·Et2O induced an bathochromic shift and isosbestic points15 at 275 and 380 nm, which are indicative for an equilibrium among the starting 7, BF3, and the complex formed from 7 and BF3 in an Et2O solution.

3. CONCLUSIONS In summary, we have demonstrated the synthesis and photophysical properties of 5-N-arylamino-4-methylthiazoles. The target compounds were generated using a three-step synthesis from commercially available 4-methylthiazole involving (i) a direct C−H arylation at the 2-position of the thiazole core, (ii) a bromination, and (iii) a Buchwald−Hartwig amination. The longest-wavelength absorption maxima were comparable to those of previously reported 5-N-arylamino-4arythiazoles. Their fluorescence wavelengths strongly depended on the substituents on the aromatic ring at the 2-positions and on those of the nitrogen atom at the 5-position of the thiazole

Figure 5. Energy levels and Kohn−Sham plots for the frontier molecular orbitals of 4ab, 4b, and 4d.

used the long-range corrected CAM-B3LYP13 instead of the B3LYP functional for the time-dependent density functional theory (TD-DFT) calculations of the UV−vis maximum absorption wavelengths of 4ab, 4b, and 4d (Table 6). These were observed at 329 nm (4ab), 346 nm (4b), and 380 nm (4d) and assigned predominantly to the HOMO → LUMO transitions. The calculated bathochromic shifts from 4ab to 4d Table 6. Results of the DFT Calculationsa

excitation energy (eV) 4

λabs (nm)

f

HOMO-1 (eV)

HOMO (eV)

LUMO (eV)

4ab

329

0.4444

−7.77

−6.69

−0.60

3.76

4b

346

0.4539

−8.11

−6.88

−1.08

3.59

4db

380

0.5468

−8.28

−6.97

−1.90

3.26

HOMO−LUMO: 0.67 HOMO-1−LUMO: −0.13 HOMO−LUMO: 0.66 HOMO-1−LUMO: −0.13 HOMO−LUMO: 0.63 HOMO-1−LUMO: −0.15 HOMO−LUMO+1: 0.26

a

Results of the TD-DFT calculations at the CAM-B3LYP/6-31+G(d,p) level of theory were carried out using the structures optimized at the B3LYP/6-31+G(d,p) level of theory. Gas-phase energies are shown. bThe energy level corresponding to the LUMO+1 was calculated to be −0.41 eV. D

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4.5. Characterization Data. 4.5.1. 4-Methyl-2-(4trifluoromethyl)phenylthiazole (2b). Yellow liquid. IR (KBr): 2926, 1930, 1616, 1515, 1451, 1407, 1380, 1323, 1246, 1168 cm−1. 1H NMR (CDCl3): δ 2.43 (s, 3H, CH3), 6.96 (s, 1H, Ar), 7.68 (d, J = 8.4 Hz, 2H, Ar), 8.04 (d, J = 8.4 Hz, 2H, Ar). 13C NMR (CDCl3): δ 17.3, 114.7, 125.4 (q, JC−F = 272.5 Hz), 126.0 (q, JC−F = 3.8 Hz), 126.7, 131.5(q, JC−F = 32.9 Hz) 136.3, 154.5, 165.7. 19F NMR (CDCl3): δ −62.7. MS (EI): m/z 243 [M+], calcd for C11H8F3NS. HRMS: calcd for C11H8F3NS, 243.0330; found, 243.0341. 4.5.2. 4-Methyl-2-(3,5-bis(trifluoromethyl)phenyl)thiazole (2c). Yellow liquid. IR (KBr): 3095, 2924, 2855, 1809, 1620, 1522, 1483, 1366, 1281, 899 cm−1. 1H NMR (CDCl3): δ 2.54 (s, 3H, CH3), 7.01 (s, 1H, Ar), 7.89 (s, 1H, Ar), 8.37 (s, 2H, Ar). 13C NMR (CDCl3): δ 17.3, 115.4, 122.1 (q, JC−F = 272.9 Hz), 123.2 (q, JC−F = 3.7 Hz), 126.4, 132.5 (q, JC−F = 33.6 Hz), 135.8, 155.0, 163.8. 19F NMR (CDCl3): δ −62.9. MS (EI): m/z 311 [M+], calcd for C12H7F6NS. HRMS: calcd for C12H7F6NS, 311.0203; found, 311.0196. 4.5.3. 4-Methyl-2-(4-nitro)phenylthiazole (2d). Yellow solid. Mp: 100−105 °C. IR (KBr): 3099, 1597, 1507, 1445, 1244, 1106, 1002, 852, 753, 727 cm−1. 1H NMR (CDCl3): δ 2.55 (s, 3H, CH3), 7.04 (s, 1H, Ar), 8.10 (d, J = 8.7 Hz, 2H, Ar), 8.29 (d, J = 8.7 Hz, 2H, Ar). 13C NMR (CDCl3): δ 17.3, 115.9, 124.4, 127.0, 139.3, 148.3, 155.2, 164.4; MS (EI): m/z 220 [M+], calcd for C20H8N2O2S. HRMS: calcd for C10H8N2O2S. 220.0306; found, 220.0296. 4.5.4. 4-Methyl-2-(2-thienyl)-thiazole (2e). Yellow liquid. IR (KBr): 3104, 2920, 1546, 1513, 1413, 1302, 1230, 1136, 974, 840 cm−1. 1H NMR (CDCl3): δ 2.47 (s, 3H, CH3), 6.78 (s, 1H, Ar), 7.06 (d, J = 5.3 Hz, 1H, Ar), 7.36 (d, J = 5.3 Hz, 1H, Ar) 7.48 (d, J = 3.4 Hz, 1H Ar). 13C NMR (CDCl3): δ 17.3, 112.7, 126.3, 127.4, 127.9, 137.6, 153.6, 161.2. MS (EI): m/z 181 [M+], calcd for C8H7NS2. HRMS: calcd for C8H7NS2. 181.0020; found, 181.0025. 4.5.5. 5-Bromo-4-methyl-2-(4-trifluoromethyl)phenylthiazole (3b). White solid. Mp: 63−65 °C. IR (KBr): 1614, 1513, 1447, 1407, 1336, 842, 773, 674, 633, 597 cm−1. 1H NMR (CDCl3): δ 2.48 (s, 3H, CH3), 7.69 (d, J = 8.3 Hz, 2H, Ar), 7.96 (d, J = 8.3 Hz, 2H, Ar). 13C NMR (CDCl3): δ 15.8, 105.6, 122.5 (q, JC−F = 272.5 Hz), 126.1(q, JC−F = 3.8 Hz), 126.4, 131.9 (q, JC−F = 32.9 Hz), 136.3, 153.5, 165.0. 19F NMR (CDCl3): δ −62.7; MS (EI): m/z 323 (94, M+ + 2), 321 (100, M+), calcd for C11H7BrF3NS. HRMS: calcd for C11H7BrF3NS, 320.9435, 322.9414; found, 320.9416, 322.9404. 4.5.6. 5-Bromo-4-methyl-2-(3,5-bis(trifluoromethyl)phenyl)thiazole (3c). White solid. Mp: 99−101 °C. IR (KBr): 1861, 1619, 1522, 1479, 1435, 1365, 1286, 897, 846, 782 cm−1. 1H NMR (CDCl3): δ 2.48 (s, 3H, CH3), 7.89 (s, 1H, Ar), 8.26 (s, 2H, Ar). 13C NMR (CDCl3): δ 15.8, 106.5, 121.7 (q, JC−F = 273.2 Hz), 123.4 (q, JC−F = 3.8 Hz), 126.0, 132.8 (q, JC−F = 33.6 Hz), 135.1, 153.9, 163.1. 19F NMR (CDCl3): δ −62.9. MS (EI): m/z 391 (100, M+ + 2), 389 (99, M+), calcd for C12H6BrF6NS. HRMS: calcd for C12H6BrF6NS, 388.9309, 390.9288; found, 388.9316, 390.9306. 4.5.7. 5-Bromo-4-methyl-2-(4-nitro)phenylthiazole (3d). Yellow solid. Mp: 148−160 °C. IR (KBr): 1594, 1520, 1338, 1283, 1106, 1043, 1003, 851, 752, 687 cm−1. 1H NMR (CDCl3): δ 2.49 (s, 3H, CH3), 8.01 (d, J = 8.88 Hz, 2H, Ar), 8.29 (d, J = 8.88 Hz, 2H, Ar). 13 C NMR (CDCl3): δ 15.9, 107.0, 124.5, 126.8, 138.6, 148.5, 154.1, 163.8. MS (EI): m/z 300 (100, M+ + 2), 298 (99, M+), calcd for C 10 H7 BrN 2 O 2 S. HRMS: calcd for C 10 H7 BrN 2 O 2 S, 297.9412, 299.9391; found, 297.9404, 299.9379. 4.5.8. 5-Bromo-4-methyl-2-(2-thienyl)thiazole (3e). Yellow solid. Mp: 63−66 °C. IR (KBr): 1509, 1411, 1236, 1079, 1030, 957, 843, 826, 698, 630 cm−1. 1H NMR (CDCl3): δ 2.42 (s, 3H, CH3), 7.06 (s, 1H, J = 5.16 Hz, Ar), 7.39 (d, 1H, J = 5.16 Hz, Ar), 7.42 (d, 1H, J = 3.72 Hz, Ar). 13C NMR (CDCl3): δ 15.8, 103.2, 126.6, 128.0, 130.8, 137.0, 152.4, 160.8. MS (EI): m/z 261 (100, M+ + 2), 259 (89, M+), calcd for C8H6BrNS2 HRMS: calcd for C8H6BrNS2, 258.9125, 260.9105; found, 258.9113, 260.9094. 4.5.9. 4-Methyl-2-phenyl-5-(methylphenylamino)thiazole (4aa). Yellow liquid. IR (KBr): 2924, 1600, 1559, 1497, 1458, 1378, 1341, 1233, 1126, 1001, 914, 750, 690 cm−1. 1H NMR (CDCl3): δ 2.28 (s, 3H, CCH3), 3.28 (s, 3H, NCH3), 6.77 (d, J = 8.1 Hz, 2H, Ar), 6.85 (t, J = 7.6 Hz, 1H, Ar), 7.25 (m, 2H, Ar), 7.41 (t, J = 7.6 Hz, 3H, Ar),

core. In particular, the nitro group bathochromically shifted the emission wavelength of 4d by 271 nm relative to the unsubstituted analogue (4aa). DFT calculations indicated that the lowering of the LUMO energy levels of the thiazoles with electron-accepting groups was more pronounced than the change in the energy level of the HOMOs. Studies on further applications of these fluorescent 5-N-arylaminothiazoles are currently in progress.

4. EXPERIMENTAL SECTION 4.1. General Remarks. All manipulations were carried out under an argon atmosphere. Unless otherwise noted, reagents are commercially available and were used without purification. Toluene and 1,4-dioxane were distilled from sodium metal. The 1H and 13 C NMR spectra were recorded in CDCl3. Chemical shifts of protons are reported in δ values referenced to tetramethylsilane as an internal standard in CDCl3, and the following abbreviations were used: s, singlet; d, doublet; t, triplet; m, multiplet. The HRMS spectra were recorded on a double-focusing mass spectrometer (EI). Column chromatography was performed on silica gel 60 N (spherical neutral) 100−210 μm. Flash column chromatography was performed on silica gel 60 N (spherical neutral) 40−50 μm. Preparative recycling gel permeation chromatography (GPC) was performed with JAIGEL-1H and -2H columns and chloroform as an eluent. All calculations were carried out using the GAUSSIAN 09 program.16 Geometry optimization was performed with hybrid density functional theory (DFT) at the B3LYP17 level, by using the 6-31+G(d,p) basis set for all atoms. The UV/vis absorption spectra of optimized geometries were calculated with the time-dependent (TD) DFT method at the CAM-B3LYP18 level. 4.2. Typical Procedure for Direct C−H Arylation: Synthesis of 4-Methyl-2-(4-trifluoromethyl)phenylthiazole (2b). Pd(OAc)2 (5.6 mg, 0.025 mmol, 5 mol %), CuI (190 mg, 1.0 mmol, 2.0 equiv), 4-(trifluoromethyl)-1-iodobenzene (5b; 0.07 mL, 0.5 mmol, 1.0 equiv), 4-methylthiazole (1a; 50 mg, 0.5 mmol, 1.0 equiv), and DMF (1.0 mL) were placed in a screwcapped test tube. The reaction mixture was stirred at 140 °C under Ar for 24 h. The mixture was then cooled to room temperature, filtered through a Celite pad, and concentrated in vacuo. The residue was purified by gel permeation chromatography (GPC) to give 4-methyl-2(4-trifluoromethyl)phenylthiazole (2b) in 82% yield as a white solid: mp 43−48 °C; Rf = 0.65 (hexane/ethyl acetate 4/1). 4.3. Typical Procedure for Bromination: Synthesis of 5Bromo-4-methyl-2-(4-trifluoromethyl)phenylthiazole (3b). To a solution of 4-methyl-2-(4-trifluoromethyl)phenylthiazole (2b; 61 mg, 0.25 mmol) in acetic acid (0.05 mL) was added bromine (0.015 mL, 0.3 mmol) at 0 °C. The mixture was slowly warmed to room temperature and stirred for 1 h. To the reaction mixture was added aqueous saturated NaOH solution, and the resulting solution was extracted with CH2Cl2. The organic layer was dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by short silica gel column chromatography to give 5-bromo-4-methyl-2-(4-trifluoromethyl)phenylthiazole (3b) in 99% yield as a white solid: mp 63−65 °C; Rf = 0.88 (hexane/ethyl acetate 4/1). 4.4. Typical Procedure for Buchwald−Hartwig Amination: Synthesis of 4-Methyl-2-phenyl-5-(methylphenylamino)thiazole (4aa). 5-Bromo-4-methyl-2-phenylthiazole (3a; 126 mg, 0.5 mmol), Pd2(dba)3 (46 mg, 0.05 mmol), Xantphos (58 mg, 0.1 mmol,), Cs2CO3 (326 mg, 1.0 mmol), toluene (2 mL), and N-methylaniline (6a; 0.17 mL, 1.5 mmol) were placed in a screwcapped test tube. The reaction mixture was degassed by freeze− degassing and then stirred at 130 °C under Ar for 17 h. The mixture was then cooled to room temperature and filtered through a Celite pad and concentrated in vacuo. The residue was purified by gel permeation chromatography (GPC) to give 5-(methylphenylamino)-4-methyl-2phenylthiazole (4aa) in 15% yield as a yellow liquid: Rf = 0.48 (hexane: ethyl acetate =10:1). E

DOI: 10.1021/acs.organomet.7b00128 Organometallics XXXX, XXX, XXX−XXX

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Organometallics 7.89 (d, J = 7.6 Hz, 2H, Ar). 13C NMR (CDCl3): δ 14.6, 40.7, 113.8, 119.1, 126.2, 129.0, 129.2, 129.9, 134.2, 141.0, 148.5, 148.9, 163.7; MS (EI): m/z 280 (M+), calcd for C17H16N2S. HRMS: calcd for C17H16N2S, 280.1034; found, 280.1019. 4.5.10. 4-Methyl-2-phenyl-5-(diphenylamino)thiazole (4ab). Yellow liquid. IR (KBr): 3434, 2923, 1589, 1548, 1491, 1456, 1377, 1290, 751, 692 cm−1. 1H NMR (CDCl3): δ 2.20 (s, 3H, CH3), 7.03 (t, J = 7.5 Hz, 2H, Ar), 7.11 (d, J = 7.5 Hz, 4H, Ar), 7.28 (m, 4H, Ar), 7.40 (m, 3H, Ar), 7.88 (m, 2H, Ar). 13C NMR (CDCl3): δ 14.8, 121.5, 123.0, 126.1, 128.9, 129.8, 129.9, 134.2, 139.3, 146.8, 148.6, 163.5. MS (EI): m/z 342 (M+) calcd for C22H18N2S. HRMS: calcd for C22H18N2S, 342.1191; found, 342.1190. 4.5.11. 4-Methyl-2-(4-trifluoromethylphenyl)-5-(diphenylamino)thiazole (4b). Yellow liquid. IR (KBr): 1716, 1615, 1589, 1547, 1491, 1446, 1406, 1378, 1323, 1290 cm−1. 1H NMR (CDCl3): δ 2.19 (s, 3H, CH3), 7.08 (m, 6H, Ar), 7.28 (m, 4H, Ar), 7.66 (d, 2H, J = 8.6 Hz, Ar), 7.97 (d, J = 8.6 Hz, 2H, Ar). 13C NMR (CDCl3): δ 14.9, 121.7, 123.2, 125.4 (q, JC−F = 272.2 Hz), 125.9, 126.2, 129.5 (q, JC−F = 3.8 Hz), 131.3 (q, JC−F = 32.6 Hz), 137.2, 140.7, 146.7, 148.8, 161.1. 19F NMR (CDCl3): δ −62.6; MS (EI): m/z 410 (M+), calcd for C23H17F3N2S. HRMS: calcd for C23H17F3N2S, 410.1065; found, 410.1051. 4.5.12. 4-Methyl-2-(3,5-bis(trifluoromethyl)phenyl)-5(diphenylamino)thiazole (4ca). White solid. Mp: 100−103 °C. IR (KBr): 2922, 1590, 1494, 1370, 1283, 1230, 1129, 1040, 905, 846 cm−1. 1 H NMR (CDCl3): δ 2.20 (s, 3H, CH3), 7.09 (m, 6H, Ar), 7.31 (m, 4H, Ar), 7.86 (s, 1H, Ar), 8.30 (s, 2H, Ar). 13C NMR (CDCl3): δ 14.9, 121.8, 123.5 (q, JC−F = 271.5 Hz), 125.8, 122.8 (q, JC−F = 3.8 Hz), 125.9, 129.5, 132.4 (q, JC−F = 33.8 Hz), 136.0, 141.7, 146.7, 148.8, 158.9. 19F NMR (CDCl3): δ −62.9. MS (EI): m/z 478 (M+), calcd for C24H16F6N2S. HRMS: calcd for C24H16F6N2S, 478.0938; found, 478.0954. 4.5.13. 4-Methyl-2-(3,5-bis(trifluoromethyl)phenyl)-5-(4dimethoxyphenylamino)thiazole (4cb). Yellow liquid. IR (KBr): 2953, 1505, 1478, 1369, 1333, 1280, 1243, 1180, 1138, 1038, 894 cm−1. 1 H NMR (CDCl3): δ 2.19 (s, 3H, CH3), 3.79 (s, 6H, OMe), 6.84 (d, J = 8.9 Hz, 4H, Ar), 7.00 (d, J = 8.9 Hz, 4H, Ar), 7.84 (s, 1H, Ar), 8.28 (s, 2H, Ar). 13C NMR (CDCl3): δ 15.0, 55.6, 114.8, 123.2 (q, JC−F = 3.8 Hz), 124.6 (q, JC−F = 273.2 Hz), 125.7, 125.6, 132.4 (q, JC−F = 33.6 Hz), 136.2, 140.8, 143.3, 147.1, 155.9, 157.4. 19F NMR (CDCl3): δ −62.9. MS (EI): m/z 538 (M+), calcd for C26H20F6N2O2S. HRMS: calcd for C26H20F6N2O2S, 538.1150; found, 538.1172. 4.5.14. 4-Methyl-2-(4-nitrophenyl)-5-(diphenylamino)thiazole (4d). Red solid. Mp: 165−168 °C. IR (KBr): 1594, 1514, 1491, 1437, 1339, 1106, 860, 753, 691, 691 cm−1. 1H NMR (CDCl3): δ 2.19 (s, 3H, CH3), 7.07 (m, 6H, Ar), 7.30 (m, 4H, Ar), 8.01 (d, J = 8.98 Hz, 2H, Ar), 8.26 (d, J = 8.98 Hz, 2H, Ar); 13C NMR (CDCl3): δ 14.9, 121.8, 123,5, 123.4, 126.5, 129.5, 139.6, 142.2, 146.7, 148.2, 149.1, 159.4. MS (EI): m/z 387 (M+), calcd for C22H17N3O2S. HRMS: calcd for C22H17N3O2S, 387.1041; found, 387.1052. 4.5.15. 4-Methyl-5-(diphenylamino)-2-(2-thienyl)thiazole (4e). White solid. Mp: 104−110 °C. IR (KBr): 2920, 1586, 1558, 1489, 1412, 1257, 1075, 1027, 838, 756 cm−1. 1H NMR (CDCl3): δ 2.14 (s, 3H, CH3), 7.07 (m, 7H, Ar), 7.27 (m, 4H, Ar), 7.36 (m, 2H, Ar). 13 C NMR (CDCl3): δ 14.7, 121.5, 123.0, 126.0, 127.4, 127.9, 129.4, 138.2, 138.5, 146.7, 148.1, 157.4. MS (EI): m/z 348 (M+), calcd for C20H16N2S2. HRMS: calcd for C20H16N2S2, 348.0755; found, 348.0770. 4.5.16. 4-Methyl-2-(4-aminophenyl)-5-(diphenylamino)thiazole (7). White solid. Mp: 193−196 °C. IR (KBr): 2925, 1715, 1601, 1490, 1363, 1304, 1261, 1223, 1179, 829 cm−1. 1H NMR (CDCl3): δ 2.16 (s, 3H, CH3), 3.8−4.0 (brs, 2H, NH2), 6.87 (d, J = 8.6 Hz, 2H, Ar), 7.01 (t, J = 7.3 Hz, 2H, Ar), 7.10 (d, J = 7.5 Hz, 4H, Ar), 7.27 (m, 4H, Ar) 7.67(d, J = 8.5 Hz, 2H). 13C NMR (CDCl3): δ 14.7, 115.0, 121.4, 122.7, 124.9, 127.6, 129.3, 137.3, 146.8, 148.2, 148.3, 164.5; MS (EI): m/z 357 (M+), calcd for C22H19N3S. HRMS: calcd for C22H19N3S, 357.1300; found, 357.1298.

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Ball and stick representation of 4d, change in fluorescence spectra of 7 by addition of BF3·Et2O, and 1H and 13C NMR spectra of all compounds (PDF) Cartesian coordinates for the calculated structures (XYZ)

AUTHOR INFORMATION

Corresponding Author

*E-mail for T.M.: [email protected]. ORCID

Toshiaki Murai: 0000-0003-4945-0996 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the following grants-in-aid: Scientific Research on Innovative Areas (MEXT), “StimuliResponsive Chemical Species for the Creation of Functional Molecules“ [2408], 15H00933 as well as ACT-C from the Japan Science and Technology Agency (JST).

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REFERENCES

(1) (a) Wrona-Piotrowicz, A.; Plazuk, D.; Zakrzewski, J.; Metivier, R.; Nakatani, K.; Makal, A. Dyes Pigm. 2015, 121, 290. (b) Zheng, M.-H.; Hu, X.; Yang, M.-Y.; Jin, J.-Y. J. Fluoresc. 2015, 25, 1831. (c) Sekar, N.; Umape, P. G.; Patil, S. R. J. Fluoresc. 2015, 25, 1787. (d) Li, T.; Gao, J.; Cui, Y.; Zhong, C.; Ye, Q.; Han, L. J. Photochem. Photobiol., A 2015, 303−304, 91. (e) Zhang, Q.; Li, Y.; Lu, Y.; Zhang, H.; Li, M.; Yang, Y.; Wang, J.; Chen, Y.; Li, C. Polymer 2015, 68, 227. (f) Kim, B.-Y.; Kim, H.-S.; Helal, A. Sens. Actuators, B 2015, 206, 430. (g) Zhang, X.; Jing, S.-Y.; Huang, S.-Y.; Zhou, X.-W.; Bai, J.-M.; Zhao, B.-X. Sens. Actuators, B 2015, 206, 663. (h) Tanaka, S.; Ashida, K.; Tatsuta, G.; Mori, A. Synlett 2015, 26, 1496. (i) Xi, B.; Wang, Na; Ma, B.-B.; Tao, T.; Huang, W. Tetrahedron 2015, 71, 3966. (j) Thale, P. B.; Borase, P. N.; Shankarling, G. S. Inorg. Chem. Front. 2016, 3, 977. (k) Mahesh, K.; Karpagam, S. J. Fluoresc. 2016, 26, 1457. (l) An, M.; Kim, B.-Y.; Seo, H.; Helal, A.; Kim, H.-S. Spectrochim. Acta, Part A 2016, 169, 87. (m) Wang, Y.; Yang, M.-Y.; Zheng, M.-H.; Zhao, X.-L.; Xie, Y.-Z.; Jin, J.-Y. Tetrahedron Lett. 2016, 57, 2399. (2) (a) Breul, M. A.; Pietsch, C.; Menzel, R.; Schäfer, J.; Teichler, A.; Hager, M. D.; Popp, J.; Dietzek, B.; Beckert, R.; Schubert, U. S. Eur. Polym. J. 2012, 48, 1339. (b) Tao, T.; Ma, B.-B.; Peng, Y.-X.; Wang, X.U.; Huang, W.; You, X. Z. J. Org. Chem. 2013, 78, 8669. (c) Wolfram, S.; Wurfel, H.; Habenicht, S. H.; Lembke, C.; Richter, P.; Birckner, E.; Beckert, R.; Pohnert, G. Beilstein J. Org. Chem. 2014, 10, 2470. (d) Breul, A. M.; de Moraes, I. R.; Menzel, R.; Pfeffer, M.; Winter, A.; Hager, M. D.; Rau, R.; Dietzek, B.; Beckert, R.; Schubert, U. S. Polym. Chem. 2014, 5, 2715. (e) Chowdhury, S. R.; Maini, R.; Dedkova, L. M.; Hecht, S. M. Bioorg. Med. Chem. Lett. 2015, 25, 4715. (f) Chowdhury, S. R.; Chauhan, P. S.; Dedkova, L. M.; Bai, X.; Chen, S.; Talukder, P.; Hecht, S. M. Biochemistry 2016, 55, 2427. (g) Kammel, R.; Tarabov, D.; Machalicky, O.; Nepras, M.; Frumarova, B.; Hanusek, J. Dyes Pigm. 2016, 128, 101. (h) Yang, M.-Y.; Zhao, X.L.; Zheng, M.-H.; Wang, Y.; Jin, J.-Y. J. Fluoresc. 2016, 26, 1653. (3) (a) Sun, W.; Zhou, C.; Xu, C.-H.; Fang, C.-J.; Zhang, C.; Li, Z.X.; Yan, C.-H. Chem. - Eur. J. 2008, 14, 6342. (b) Li, Z.-X.; Xu, C.-H.; Sun, W.; Bai, Y.-C.; Zhang, C.; Fang, C. J.; Yan, C.-H. New J. Chem. 2009, 33, 853. (c) Zheng, M.-H.; Zhang, M.-M.; Li, H.-H.; Jin, J.-Y. J. Fluoresc. 2012, 22, 1421. (d) Zheng, M.-H.; Sun, W.; Jin, J.-Y.; Yan, C.H. J. Fluoresc. 2014, 24, 1169. (e) Davydova, Y. A.; Sokolenko, T. M.; Vlasenko, Y. G.; Yagupolskii, Y. L. Chem. Heterocycl. Compd. 2015, 51, 80. (f) Nakashima, T.; Tsuchie, K.; Kanazawa, R.; Li, R.; Iijima, S.; Galangau, O.; Nakagawa, H.; Mutoh, K.; Kobayashi, Y.; Abe, J.; Kawai, T. J. Am. Chem. Soc. 2015, 137, 7023. (g) Hu, T.; Li, Z.; Wang, T.; Zeng, H. J. Heterocyclic Chem. 2016, 53, 109. (4) (a) Murai, T.; Hori, F.; Maruyama, T. Org. Lett. 2011, 13, 1718. (b) Murai, T.; Yamaguchi, K.; Hori, F.; Maruyama, T. J. Org. Chem.

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DOI: 10.1021/acs.organomet.7b00128 Organometallics XXXX, XXX, XXX−XXX

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Organometallics 2014, 79, 4930. (c) Yamaguchi, K.; Murai, T.; Hasegawa, S.; Miwa, S.; Kutsumizu, S.; Maruyama, T.; Sasamori, T.; Tokitoh, N. J. Org. Chem. 2015, 80, 10742. (d) Yamaguchi, K.; Murai, T.; Guo, J.-D.; Sasamori, T.; Tokitoh, N. ChemistryOpen 2016, 5, 434. (5) (a) Pivsa-Art, S.; Satoh, T.; Kawamura, Y.; Minura, M.; Nomura, M. Bull. Chem. Soc. Jpn. 1998, 71, 467. (b) Bellina, F.; Cauteruccio, S.; Rossi, R. Eur. J. Org. Chem. 2006, 2006, 1379. (c) Nandurkar, N. S.; Bhanushali, M. J.; Bhor, M. D.; Bhanage, B. M. Tetrahedron Lett. 2008, 49, 1045. (d) Canivet, J.; Yamaguchi, J.; Ban, I.; Itami, K. Org. Lett. 2009, 11, 1733. (e) Tani, S.; Uehara, T. N.; Yamaguchi, J.; Itami, K. Chem. Sci. 2014, 5, 123. (6) (a) Ceulemans, E.; Dyall, L. K.; Dehaen, W. Tetrahedron 1999, 55, 1977. (b) Vachal, P.; Toth, L. M. Tetrahedron Lett. 2004, 45, 7157. (7) For reviews, see: (a) Lundgren, R. J.; Stradiotto, M. Aldrichim. Acta 2012, 45, 59. (b) Sherman, A. R.; Murugan, R. Adv. Heterocycl. Chem. 2015, 114, 227. (8) Nowak, M.; Malinowski, Z.; Jozwiak, A.; Fornal, E.; Blaszczyk, A.; Kontek, R. Tetrahedron 2014, 70, 5153. (9) Personal Communication to the Cambridge Structural Database. A CIF file is available from the CSD, where it has been deposited as “CSD Communications” (Toshiaki Murai, 2017, CCDC 1539473). (10) Crawford, J. J.; Ortwine, D. F.; Wei, B.; Young, W. B. PCT Int. Appl. 2013067274, 2013. (11) For examples on strong bathochromic shifts as a result of the presence of nitro groups, see: (a) Gruen, H.; Gorner, H. J. Phys. Chem. 1989, 93, 7144. (b) Kotaka, H.; Konishi, G.; Mizuno, K. Tetrahedron Lett. 2010, 51, 181. (c) Bolduc, A.; Dong, Y.; Guérin, A.; Skene, W. G. Phys. Chem. Chem. Phys. 2012, 14, 6946. (d) Karthik, S.; Ajantha, J.; Nagaraja, C. M.; Easwaramoorthi, S.; Gandhi, T. Org. Biomol. Chem. 2016, 14, 10255. (e) Habenicht, S. H.; Siegmann, M.; Kupfer, S.; Kübel, J.; Weiß, D.; Cherek, D.; Möller, U.; Dietzek, B.; Gräfe, S.; Beckert, R. Methods Appl. Fluoresc. 2015, 3, 025005. (12) Reichardt, C. Solvents and Solvent Effects in Organic Chemistry; Wiley-VCH: Weinheim, Germany, 1988. (13) For details, see the Supporting Information. (14) The synthetic importance of the coordination of BF3 to aniline derivatives has been proven for their ortho lithiation; see: Kessar, S. V.; Singh, P.; Singh, K. N.; Bharatam, P. V.; Sharma, A. K.; Lata, S.; Kaur, A. Angew. Chem., Int. Ed. 2008, 47, 4703. (15) For recent examples of discussions on equilibrium on the basis of isosbestic points, see: (a) Chao, D.; Mu, W. Chem. Lett. 2016, 45, 27. (b) AL-Thabaiti, S. A.; Aazam, E. S.; Khan, Z.; Bashir, O. Spectrochim. Acta, Part A 2016, 156, 28. (c) Dostani, M.; Kianfar, A. H.; Mahmood, W. A. K.; Dinari, M.; Farrokhpour, H.; Sabzalian, M. R.; Abyar, F.; Azarian, M. H. Spectrochim. Acta, Part A 2017, 180, 144. (d) Khadem, M.; Zhao, Y. Chem. Commun. 2017, 53, 1821. (16) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Keith, T.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, revision B.01; Gaussian, Inc., Wallingford, CT, 2010. (17) (a) Becke, A. D. Phys. Rev. A: At., Mol., Opt. Phys. 1988, 38, 3098. (b) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (c) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B: Condens. Matter Mater. Phys. 1988, 37, 785. (18) Yanai, T.; Tew, D.; Handy, N. Chem. Phys. Lett. 2004, 393, 51.

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DOI: 10.1021/acs.organomet.7b00128 Organometallics XXXX, XXX, XXX−XXX